中华烧伤与创面修复杂志

Rehabilitation strategy for the improvement of long-term outcomes of patients after sepsis

Yao Yongming, Zhang Hui

2022, 38(3): 201-206. doi: 10.3760/cma.j.cn501120-20211004-00344

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Survivors of sepsis still face high risks of secondary infection and mortality after hospital discharge. Meanwhile, the persistent cognitive, psychological, and physical disorders affect their long-term outcomes and life qualities. In the current review, we analyze the factors for the poor outcomes and discuss the beneficial rehabilitation strategies to improve the long-term outcomes of patients after sepsis, including psychological intervention, early mobility, nutrition support, and immune modulation, etc.

Predictive values of serum 8-hydroxydeoxyguanosine on disease progression and prognosis of patients with sepsis

Chen Xiaorong, Jiang Danwei, Tang Yahui, Xu Chang, Zhi Shaoce, Hong Guangliang, Lu Zhongqiu, Zhao Guangju

2022, 38(3): 207-214. doi: 10.3760/cma.j.cn501120-20210910-00311

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Objective To investigate the values of serum 8-hydroxydeoxyguanosine (8-OHdG) in predicting disease progression and prognosis of patients with sepsis. Methods The prospective observational research methods were used. A total of 124 patients with sepsis who met the inclusion criteria were admitted to the Department of Emergency of the First Affiliated Hospital of Wenzhou Medical University from April 2015 to July 2016, including 79 males and 45 females, aged (62±15) years. The sepsis-related organ failure assessment (SOFA) scores of all patients on admission and on the second day of admission and their difference (ΔSOFA) were calculated. The patients were divided into non-progression group with ΔSOFA score<2 (n=101) and progression group with ΔSOFA score ≥2 (n=23), and according to the survival during hospitalization, the patients were divided into survival group (n=85) and death group (n=39). Data of patients between non-progression group and progression group, survival group and death group were compared, including the gender, age, days in emergency intensive care unit (ICU), smoking, hypertension, diabetes mellitus, serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission, and serum 8-OHdG within 24 h of admission. The multivariate logistic regression analysis was used to screen the independent risk factors of disease progression and death during hospitalization in 124 patients with sepsis, the receiver's operating characteristic (ROC) curves were drawn according to the independent risk factors, and the area under the curve (AUC), the best threshold, and the sensitivity and specificity under the best threshold were calculated. The patients were divided into high 8-OHdG group (n=35) and low 8-OHdG group (n=89) according to the best threshold in ROC curve of death during hospitalization. The data including the gender, age, SOFA score on admission, SOFA score on the second day of admission, and ΔSOFA score of patients in the two groups were compared. The survival rates of patients within 90 d of admission in the two groups were compared by the Kaplan-Meier method. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, chi-square test, and Log-rank test. Results The gender, age, days in emergency ICU, smoking, complicated with hypertension, complicated with diabetes mellitus, serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission of patients in non-progression group and progression group were similar (P>0.05). The serum 8-OHdG within 24 h of admission of patients in progression group was significantly higher than that in non-progression group (Z=-2.31, P<0.05). Multivariate logistic regression analysis showed that the serum 8-OHdG within 24 h of admission was the independent risk factor for disease progression of 124 patients with sepsis (odds ratio=1.06, with 95% confidence interval of 1.01-1.11, P<0.05). The AUC under the ROC curve of serum 8-OHdG within 24 h of admission to predict disease progression of 124 patients with sepsis was 0.65 (with 95% confidence interval of 0.52-0.79, P<0.05), the optimal threshold was 32.88 ng/mL, and the sensitivity and specificity under the optimal threshold was 52.2% and 79.2%, respectively. The gender, age, days in emergency ICU, smoking, complicated with hypertension, complicated with diabetes mellitus, and serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission of patients in survival group and death group were similar (P>0.05). The serum 8-OHdG within 24 h of admission of patients in death group was significantly higher than that in survival group (Z=-2.37, P<0.05). Multivariate logistic regression analysis showed that the serum 8-OHdG within 24 h of admission was the independent risk factor for death of 124 patients with sepsis (odd ratio=1.04, with 95% confidence interval of 1.00-1.09, P<0.05). The AUC under the ROC curve of serum 8-OHdG within 24 h of admission to predict death of patients during hospitalization was 0.63 (with 95% confidence interval of 0.52-0.75, P<0.05), the optimal threshold was 32.43 ng/mL, the sensitivity and specificity under the optimal threshold was 51.3% and 84.7%, respectively. The gender and age of patients in high 8-OHdG group and low 8-OHdG group were similar (P>0.05). The SOFA score on admission, SOFA score on the second day of admission, and ΔSOFA score of patients in high 8-OHdG group were significantly higher than those in low 8-OHdG group (with Z values of -2.49, -3.01, and -2.64, respectively, P<0.05 or P<0.01). The survival rate within 90 d of admission of patients in low 8-OHdG group was significantly higher than that in high 8-OHdG group (χ²=14.57, P<0.01). Conclusions Serum 8-OHdG level is an independent risk factor for disease progression and death in sepsis patients with limited ability for predicting disease progression and prognosis of sepsis of patients. The patients with higher serum 8-OHdG level have higher death risk within 90 d of admission.

Effects of exosomes from human adipose-derived mesenchymal stem cells on inflammatory response of mouse RAW264.7 cells and wound healing of full-thickness skin defects in mice

Shen Kuo, Wang Xujie, Liu Kaituo, Li Shaohui, Li Jin, Zhang Jinxin, Wang Hongtao, Hu Dahai

2022, 38(3): 215-226. doi: 10.3760/cma.j.cn501120-20201116-00477

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Objective To investigate the effects of exosomes from human adipose-derived mesenchymal stem cells (ADSCs) on inflammatory response of mouse RAW264.7 cells and wound healing of full-thickness skin defects in mice. Methods The experimental research methods were adopted. The discarded adipose tissue was collected from 3 female patients (aged 10-25 years) who underwent abdominal surgery in the First Affiliated Hospital of Air Force Medical University. ADSCs were extracted from the adipose tissue by collagenase Ⅰ digestion and identified with flow cytometry. Exosomes were extracted from the human ADSCs by differential ultracentrifugation, the morphology of the exosomes was observed by transmission electron microscopy, the particle diameter of the exosomes was detected by nanoparticle tracking analyzer, and the protein expressions of CD9, CD63, tumor susceptibility gene 101 (TSG101), and β-actin were detected by Western blotting. The human ADSCs exosomes (ADSCs-Exos) and RAW264.7 cells were co-cultured for 12 h, and the uptake of RAW264.7 cells for human ADSCs-Exos was observed. The RAW264.7 cells were divided into phosphate buffer solution (PBS) group stimulated with PBS for suitable time, endotoxin/lipopolysaccharide (LPS) stimulation 2 h group, LPS stimulation 4 h group, LPS stimulation 6 h group, LPS stimulation 12 h group, and LPS stimulation 24 h group stimulated with LPS for corresponding time, with 3 wells in each group, and the mRNA expressions of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), IL-6, and IL-10 were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-PCR) method. The RAW264.7 cells were divided into PBS group, LPS alone group, and LPS+ADSCs-Exos group, with 3 wells in each group, which were dealt correspondingly for the time screened out in the previous experiment, the mRNA expressions of IL-1β, TNF-α, IL-6, IL-10, trasforming growth factor β (TGF-β,) and vascular endothelial growth factor (VEGF) were detected by real time fluorescence quantitative RT-PCR method, and the protein expressions of inducible nitric oxide synthase (iNOS) and arginase 1 (Arg1) were detected by Western blotting. Twenty-four 8-week-old male BALB/c mice were divided into PBS group and ADSCs-Exos group according to the random number table, with 12 mice in each group, and a full-thickness skin defect wound with area of 1 cm×1 cm was inflicted on the back of each mouse. Immediately after injury, the wounds of mice in the two groups were dealt correspondingly. On post injury day (PID) 1, the concentration of IL-1β and TNF-α in serum were detected by enzyme-linked immunosorbent assay, and the mRNA expressions of IL-1β, TNF-α, and IL-6 were detected by real time fluorescence quantitative RT-PCR method. On PID 3, 6, 9, 12, and 15, the wound healing was observed and the wound non-healing rate was calculated. On PID 15, the defect length of skin accessory and collagen volume fraction (CVF) were detected by hematoxylin eosin staining and Masson staining, respectively, the CD31 expression and neovascularization were detected by immunohistochemistry, and the ratio of Ki67 positive cells, the ratio of iNOS and Arg1 double positive cells, and the ratio of iNOS positive cells to Arg1 positive cells and their fluorescence intensities were detected by immunofluorescence method. The number of samples in animal experiments was 6. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, and independent sample t test. Results At 12 h of culture, the cells exhibited a typical spindle shape, which were verified as ADSCs with flow cytometry. The exosomes with a vesicular structure and particle diameters of 29-178 nm, were positively expressed CD9, CD63, and TSG101 and negatively expressed β-actin. After 12 h of co-culture, the human ADSCs-Exos were endocytosed into the cytoplasm by RAW264.7 cells. The mRNA expressions of IL-1β, TNF-α, IL-6, and IL-10 of RAW264.7 cells in LPS stimulation 2 h group, LPS stimulation 4 h group, LPS stimulation 6 h group, LPS stimulation 12 h group, and LPS stimulation 24 h group were significantly higher than those in PBS group (with t) values of 39.10, 14.55, 28.80, 4.74, 48.80, 22.97, 13.25, 36.34, 23.12, 18.71, 29.19, 41.08, 11.68, 18.06, 8.54, 43.45, 62.31, 22.52, 21.51, and 37.13, respectively, P<0.01). The stimulation 12 h with significant expressions of all the inflammatory factors was selected as the time point in the following experiment. After stimulation of 12 h, the mRNA expressions of IL-1β, TNF-α, IL-6, and IL-10 of RAW264.7 cells in LPS alone group were significantly higher than those in PBS group (with t values of 44.20, 51.26, 14.71, and 8.54, respectively, P<0.01); the mRNA expressions of IL-1β, TNF-α, and IL-6 of RAW264.7 cells in LPS+ADSCs-Exos group were significantly lower than those in LPS alone group (with t values of 22.89, 25.51, and 8.03, respectively, P<0.01), while the mRNA expressions of IL-10, TGF-β, and VEGF were significantly higher than those in LPS alone group (with t values of 9.89, 13.12, and 7.14, respectively, P<0.01). After stimulation of 12 h, the protein expression of iNOS of RAW264.7 cells in LPS alone group was significantly higher than that in PBS group and LPS+ADSCs-Exos group, respectively (with t values of 11.20 and 5.06, respectively, P<0.05 or P<0.01), and the protein expression of Arg1 was significantly lower than that in LPS+ADSCs-Exos group (t=15.01, P<0.01). On PID 1, the serum concentrations of IL-1β and TNF-α and the mRNA expressions of IL-1β, TNF-α, and IL-6 in wound tissue of mice in ADSCs-Exos group were significantly those in lower than PBS group (with t values of 15.44, 12.24, 9.24, 7.12, and 10.62, respectively, P<0.01). On PID 3, 6, 9, 12, and 15 d, the wound non-healing rates of mice in ADSCs-Exos group were (73.2±4.1)%, (53.8±3.8)%, (42.1±5.1)%, (24.1±2.8)%, and 0, which were significantly lower than (82.5±3.8)%, (71.2±4.6)%, (52.9±4.1)%, (41.5±3.6)%, and (14.8±2.5)% in PBS group, respectively (with t values of 4.77, 8.93, 5.54, 7.63, and 7.59, respectively, P<0.01). On PID 15, the defect length of skin accessory in wounds of mice in PBS group was significantly longer than that in ADSCs-Exos group (t=9.50, P<0.01), and the CVF was significantly lower than that in ADSCs-Exos group (t=9.15, P<0.01). On PID 15, the CD31 expression and the number of new blood vessels (t=12.99, P<0.01), in wound tissue of mice in ADSCs-Exos group were significantly more than those in PBS group, and the ratio of Ki67 positive cells was significantly higher than that in PBS group (t=7.52, P<0.01). On PID 15, the ratio of iNOS and Arg1 double positive cells in wound tissue of mice in PBS group was (12.33±1.97)%, which was significantly higher than (1.78±0.29)% in ADSCs-Exos group (t=13.04, P<0.01), the ratio of iNOS positive cells and the fluorescence intensity of iNOS were obviously higher than those of ADSCs-Exos group, and the ratio of Arg1 positive cells and the fluorescence intensity of Arg1 were obviously lower than those of ADSCs-Exos group. Conclusions The human ADSCs-Exos can alleviate inflammatory response of mouse RAW264.7 cells, decrease macrophage infiltration and secretion of the pro-inflammatory cytokines, increase the secretion of anti-inflammatory cytokines to promote neovascularization and cell proliferation in full-thickness skin defect wounds of mice, hence accelerating wound healing.

Investigating the effects of Modified Sijunzi Decoction on the diversity of intestinal microflora of severe scald rabbits based on 16S ribosomal RNA high-throughput sequencing

Luo Jinhua, Zhan Jianhua, Liao Wenqiang, Cheng Xing, Huang Kai

2022, 38(3): 227-235. doi: 10.3760/cma.j.cn501120-20200923-00421

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Objective To investigate the effects of Modified Sijunzi Decoction on the diversity of intestinal microflora of in severe scald rabbits based on 16S ribosomal RNA (16S rRNA) high-throughput sequencing. Methods The experimental research method was adopted. Ninety Japanese big-ear rabbits regardless gender, aged 6 to 8 months, were randomly divided into normal control group, scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group, with 18 rabbits in each group. The rabbits in normal control group were free to eat and drink, and the rabbits in scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group were intragastrically administered normal saline, 0.2 g/mL Modified Sijunzi Decoction, 1.0 g/mL Modified Sijunzi Decoction, and 5.0 g/mL Modified Sijunzi Decoction, respectively for 7 days after sustaining full-thickness scalding of 30% total body surface area. On the 1^st, 3^rd, and 7^th day after grouping, the levels of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-10 in ileal mucosa tissue of rabbits in each group were determined by enzyme-linked immunosorbent assay, and the number of samples in each group at each time point was 6. According to the above experimental results, another 9 rabbits were selected and divided into normal control group, scald alone group and scald+medium-dose group, with 3 rabbits in each group. The grouping and treatment methods of rabbits in each group were the same as before. On the 7^th day after grouping, the V3, V4 region of 16S rRNA of ileum mucosa of rabbits in three groups were sequenced by high-throughput sequencing technology. The number of quality bacteria was counted by QIME software. The classifications of phylum, class, order, family and genus of microflora were analyzed by RDP Classifier software. The α diversity (Ace, Chao1, Simpson, and Shannon indexes) and β diversity were analyzed by Illumina MiSeq sequencing technology, and the number of experiment samples in each group was 3. Data were statistically analyzed with analysis for variance of factorial design, SNK test, and Bonferroni correction. Results Compared with that in normal control group, the levels of TNF-α of ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, and scald+high-dose group on the 1^st, 3^rd, and 7^th day after grouping and scald+medium-dose group on the 1^st and 3^rd day after grouping were all significantly increased (P<0.01), the levels of IL-1β in ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, scald+medium-dose group and scald+high-dose group on the 1^st, 3^rd, and 7^th day after grouping were all significantly increased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 1^st, 3^rd, and 7^th day after grouping were all significantly decreased (P<0.01). Compared with that in scald alone group, the levels of TNF-α in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 3^rd and 7^th day after grouping, and scald+medium-dose group on the 1^st day after grouping were all significantly decreased (P<0.01), and the levels of IL-1β in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 3^rd and 7^th day after grouping and scald+medium-dose group on the 1^st day after grouping were all significantly decreased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+low-dose group on the 7^th day after grouping and scald+medium-dose group on the 1^st, 3^rd, and 7^th day after grouping and scald+high-dose group on the 3^rd and 7^th day after grouping were all significantly increased (P<0.05 or P<0.01). Compared with that in scald+low-dose group, the levels of TNF-α in ileal mucosa tissue of rabbits in medium-dose scald alone group on the 1^st, 3^rd, and 7^th day after grouping and in high-dose scald alone group on the 3^rd and 7^th day after grouping were significantly decreased (P<0.01), and the levels of IL-1β in ileal mucosa tissue of rabbits in medium-dose scald alone group on the 1^st, 3^rd, and 7^th day after grouping and in high-dose scald alone group on the 3^rd and 7^th day after grouping were all significantly decreased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+medium-dose group on the 1^st, 3^rd, and 7^th day after grouping and in scald+high-dose group on the 7^th day after grouping were all significantly increased (P<0.05 or P<0.01). Compared with that in scald medium-dose group, the levels of TNF-α in ileal mucosa tissue of rabbits in scald+high-dose group on the 1^st, 3^rd, and 7^th day after grouping were all significantly increased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+high-dose group on the 1^st, 3^rd, and 7^th day after grouping were all significantly decreased (P<0.01), and the levels of IL-1β in ileal mucosa tissue of rabbits in scald+high-dose group on the 7^th day after grouping was significantly decreased (P<0.01). Compared with that on the 1^st day after grouping, the levels of TNF-α in ileal mucosa tissue of rabbits in scald alone group on the 3^rd and 7^th day after grouping and in normal control group on the 3^rd day after grouping were all significantly increased (P<0.05 or P<0.01), and the levels of IL-1β in ileal mucosa tissue of rabbits in scald alone group both on the 3^rd and 7^th day after grouping were significantly increased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in both scald+low-dose group and scald+high-dose group on the 7^th day after grouping and scald+medium-dose group both on the 3^rd and 7^th day after grouping were significantly increased (P<0.05 or P<0.01), and the levels of TNF-α in ileal mucosa tissue of rabbits in scald+high-dose group on the 3^rd and 7^th day after grouping and in scald+medium-dose group on the 7^th day after grouping were all significantly decreased (P<0.05 or P<0.01), and the level of IL-1β in ileal mucosa tissue of rabbits in scald+medium-dose group on the 7^th day after grouping was significantly decreased (P<0.01), and the level of IL-10 in ileal mucosa tissue of rabbits in scald alone group on the 7^th day after grouping was significantly decreased (P<0.01). Compared with that on the 3^rd day after grouping, the levels of TNF-α and IL-1β in ileal mucosa tissue of rabbits in scald alone group and the levels of IL-10 in ileal mucosa tissue of rabbits in normal control group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 7^th day after grouping were all significantly increased (P<0.05 or P<0.01); and the levels of TNF-α in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 7^th day after grouping were all significantly decreased (P<0.05), and the levels of IL-1β in ileal mucosa tissue of rabbits both in scald+medium-dose group and scald+high-dose group on the 7^th day after grouping were significantly decreased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald alone group on the 7^th day after grouping was significantly decreased (P<0.01). On the 7^th day after grouping, the high-quality sequences obtained from the microflora in ileum mucosa of rabbits in normal control group, scald alone group, and scald+medium-dose group were 96 023, 107 365, and 95 921, respectively. At the classification level of phylum, class, order, family, and genus of the microflora in ileum mucosa of rabbits in three groups were all Bacteroidetes and Firmicutes, Clostridium and Bacteroidetes, Clostridium and Bacteroidetes, Rumenobacteriaceae and Clostridium and Bacteroideaceae, Clostridium and Bacteroidetes and rumen bacteria mainly, while the percentage of microflora in each group was different. There were no significant differences in Ace, Chao1, Simpson, Shannon indices (P>0.05), and no obvious difference in β diversity of microflora in ileal mucosa tissue of rabbits among three groups. Conclusions After severe scalding, the inflammatory response of rabbit ileal mucosa tissue is obvious and increased in a time-dependent manner. Modified Sijunzi Decoction can reduce inflammation with optimal therapeutic concentration of 1.0 g/mL. The technology of high-throughput sequencing can reflect the structural composition of the intestinal microflora accurately. The ileal microflora of the severe scald rabbit can be regulated by the administration of Modified Sijunzi Decoction.

Establishment and application of the tenfold rehydration formula for emergency resuscitation of adult patients after extensive burns

Shen Chuan'an, Liu Xinzhu, Li Dawei, Liu Zhaoxing, Zhang Bohan

2022, 38(3): 236-241. doi: 10.3760/cma.j.cn501120-20211109-00383

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Objective To explore the scientificity and feasibility of the tenfold rehydration formula for emergency resuscitation of adult patients after extensive burns. Methods A retrospective observational study was conducted. The total burn area (30%-100% total body surface area (TBSA)) and body weight (45-135 kg) of 170 adult patients (135 males and 35 females, aged (42±14) years) with extensive burns admitted to the Fourth Medical Center of PLA General Hospital from December 2016 to December 2019 were collected. The 6 461 pairs of simulated data obtained after pairing each body weight in 45 to 135 kg (programmed in steps of 1 kg) with each area in 30% to 100% TBSA (programmed in steps of 1%TBSA) were plugged into four recognized rehydration formulas--Parkland's formula, Brooke's formula, the 304th PLA Hospital formula, and the Third Military Medical University formula and two emergency rehydration formulas--the simplified first aid resuscitation plan for extensive burn patients proposed by the World Health Organization's Technical Working Group on Burns (TWGB, hereinafter referred to as the TWGB formula) and the tenfold rehydration formula proposed by the author of this article to calculate the rehydration rate within 8 hours after injury (hereinafter referred to as the rehydration rate), with results being displayed by a programming step of 10%TBSA for the total burn area. Taking the calculation results of four recognized rehydration formulas as the reasonable rehydration rate, the accuracy of rehydration rates calculated by two emergency rehydration formulas were calculated and compared. The body weight of 45-135 kg was divided into three segments by the results of maximum body weight at a reasonable rehydration rate calculated by the tenfold rehydration formula when the total burn area was 30% and 100% TBSA, respectively. The accuracy of rehydration rate calculated by two emergency rehydration formulas in each body weight segment was compared. When the rehydration rates calculated by two emergency rehydration formulas were unreasonable, the differences in rehydration rates between the two were compared. Statistical distribution of the aforementioned three body weight segments in the aforementioned 170 patients was counted. Using the total burn area and body weight data of the aforementioned 170 patients, the accuracy of rehydration rate calculated by two emergency rehydration formulas was calculated and compared as before. Data were statistically analyzed with McNemar test. Results When the total burn area was 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% TBSA, respectively, and the body weight was 45-135 kg, the rehydration rates calculated by two emergency rehydration formulas did not exceed the maximum of the calculated results of four recognized rehydration formulas; the rehydration rate calculated by the TWGB formula did not change accordingly with total burn area, while the rehydration rate calculated by the tenfold rehydration formula did not change accordingly with body weight. Substituting 6 461 pairs of simulated data showed that the accuracy of rehydration rate calculated by the tenfold rehydration formula was 43.09% (2 784/6 461), which was significantly higher than 2.07% (134/6 461) of the TWGB formula, χ²=2 404.80, P<0.01. When the body weights were 45-62 kg and 63-93 kg, the accuracy rates of rehydration rate calculated by the tenfold rehydration formula were 100% (1 278/1 278) and 68.42% (1 506/2 201), respectively, which were significantly higher than 0 (0/1 278) and 0.05% (1/2 201) of the TWGB formula, χ²=1 276.00, 1 501.01, P<0.01; when the body weight was 94-135 kg, the accuracy rate of rehydration rate calculated by the tenfold rehydration formula was 0 (0/2 982), which was significantly lower than 4.46% (133/2 982) of the TWGB formula, χ²=131.01, P<0.01. When the rehydration rates calculated by two emergency rehydration formulas were both unreasonable, the rehydration rate calculated by the tenfold rehydration formula was greater than that calculated by the TWGB formula in most cases, accounting for 79.3% (2 808/3 543). Among the 170 patients, the proportions of those weighing 45-62, 63-93, and 94-135 kg were 25.29% (43/170), 65.88% (112/170), and 8.82% (15/170), respectively. Among the 170 patients, the accuracy rate of rehydration rate calculated by the tenfold rehydration formula was 69.41% (118/170), which was significantly higher than 3.53% (6/170) of the TWGB formula, χ²=99.36, P<0.01. Conclusions Applying the tenfold rehydration formula to calculate the emergency rehydration rate in adults after extensive burns is simpler than four recognized rehydration formulas, and is superior to the TWGB formula. The tenfold rehydration formula is suitable for the front-line medical staffs that are not specialized in burns in pre-admission rescue of adult patients with extensive burns, which is worth popularizing.

Effect of hypochloric acid on Escherichia coli biofilm and the clinical efficacy of hypochloric acid for wounds with Escherichia coli infection

Liu Jiang, Wu Baolin, Zhu Wanzhao, Liu Jie, Wang Tong, Geng Maomao, Bai Li, Liu Yi

2022, 38(3): 242-250. doi: 10.3760/cma.j.cn501120-20201112-00471

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Objective To investigate the effect of hypochloric acid on Escherichia coli biofilm and the clinical efficacy of hypochloric acid for wounds with Escherichia coli infection. Methods One strain of Escherichia coli with the strongest bacterial biofilm forming ability among the strains isolated from specimens in 25 patients (16 males and 9 females, aged 32-67 years) from five clinical departments of the 940^th Hospital of the Joint Logistic Support Force was collected for the experimental study from September to December 2019. The Escherichia coli was cultured with hypochloric acid at 162.96, 81.48, 40.74, 20.37, 10.18, 5.09, 2.55, 1.27, 0.64, and 0.32 μg/mL respectively to screen the minimum bactericidal concentration (MBC) of hypochloric acid. The Escherichia coli was cultured with hypochloric acid at the screened MBC for 2, 5, 10, 20, 30, and 60 min respectively to screen the shortest bactericidal time of hypochloric acid. The biofilm formation of Escherichia coli was observed by scanning electron microscopy at 6, 12, 24, 48, 72, and 96 h of incubation, respectively. After 72 h of culture, hypochloric acid at 1, 2, 4, 8, and 16 times of MBC was respectively added to Escherichia coli to screen the minimum biofilm eradicate concentration (MBEC) of hypochloric acid against Escherichia coli. After hypochloric acid at 1, 2, 4, and 8 times of MBEC and sterile saline were respectively added to Escherichia coli for 10 min, the live/dead bacterial staining kit was used to detect the number of live and dead cells, with the rate of dead bacteria calculated (the number of samples was 5). From January to December 2020, 41 patients with infectious wounds meeting the inclusion criteria and admitted to the Department of Burns and Plastic Surgery of the 940^th Hospital of Joint Logistic Support Force of PLA were included into the prospective randomized controlled trial. The patients were divided into hypochloric acid group with 21 patients (13 males and 8 females, aged (46±14) years) and povidone iodine group with 20 patients (14 males and 6 females, aged (45±19) years) according to the random number table. Patients in the 2 groups were respectively dressed with sterile gauze soaked with hypochloric acid of 100 μg/mL and povidone iodine solution of 50 mg/mL with the dressings changed daily. Before the first dressing change and on the 10^th day of dressing change, tissue was taken from the wound and margin of the wound for culturing bacteria by agar culture method and quantifying the number of bacteria. The amount of wound exudate and granulation tissue growth were observed visually and scored before the first dressing change and on the 3^rd, 7^th, and 10^th days of dressing change. Data were statistically analyzed with one-way analysis of variance, Dunnett-t test, independent sample t test, Mann-Whitney U test, Wilcoxon signed-rank test, chi-square test, or Fisher's exact probability test. Results The MBC of hypochloric acid against Escherichia coli was 10.18 μg/mL, and the shortest bactericidal time of hypochloric acid with MBC against Escherichia coli was 2 min. Escherichia coli was in a completely free state after 6 and 12 h of culture and gradually aggregated and adhered with the extension of culture time, forming a mature biofilm at 72 h of culture. The MBEC of hypochloric acid against Escherichia coli was 20.36 μg/mL. The Escherichia coli mortality rates after incubation with hypochloric acid at 1, 2, 4, and 8 times of MBEC for 10 min were significantly higher than that after incubation with sterile saline (with t values of 6.11, 25.04, 28.90, and 40.74, respectively, P<0.01). The amount of bacteria in the wound tissue of patients in hypochloric acid group on the 10^th day of dressing change was 2.61 (2.20, 3.30)×10⁴ colony forming unit (CFU)/g, significantly less than 4.77 (2.18, 12.48)×10⁴ CFU/g in povidone iodine group (Z=2.06, P<0.05). The amounts of bacteria in the wound tissue of patients in hypochloric acid group and povidone iodine group on the 10^th day of dressing change were significantly less than 2.97 (2.90, 3.04)×10⁶ and 2.97 (1.90, 7.95)×10⁶ CFU/g before the first dressing change (with Z values of 4.02 and 3.92, respectively, P<0.01). The score of wound exudate amount of patients in hypochloric acid group on the 10^th day of dressing change was significantly lower than that in povidone iodine group (Z=2.07, P<0.05). Compared with those before the first dressing change, the scores of wound exudate amount of patients in hypochloric acid group on the 7^th and 10^th days of dressing change were significantly decreased (with Z values of -3.99 and -4.12, respectively, P<0.01), and the scores of wound exudate amount of patients in povidone iodine group on the 7^th and 10^th days of dressing change were significantly decreased (with Z values of -3.54 and -3.93, respectively, P<0.01). The score of wound granulation tissue growth of patients in hypochloric acid group on the 10^th day of dressing change was significantly higher than that in povidone iodine group (Z=2.02, P<0.05). Compared with those before the first dressing change, the scores of wound granulation tissue growth of patients in hypochloric acid group on the 7^th and 10^th days of dressing change were significantly increased (with Z values of -3.13 and -3.67, respectively, P<0.01), and the scores of wound granulation tissue growth of patients in povidone iodine group on the 7^th and 10^th days of dressing change were significantly increased (with Z values of -3.12 and -3.50, respectively, P<0.01). Conclusions Hypochloric acid can kill Escherichia coli both in free and biofilm status. Hypochloric acid at a low concentration shows a rapid bactericidal effect on mature Escherichia coli biofilm, and the higher the concentration of hypochloric acid, the better the bactericidal effect. The hypochloric acid of 100 μg/mL is effective in reducing the bacterial load on wounds with Escherichia coli infection in patients, as evidenced by a reduction in wound exudate and indirect promotion of granulation tissue growth, which is more effective than povidone iodine, the traditional topical antimicrobial agent.

Clinical effects of in situ perforation of preserved split scar matrix in combination with scalp transplantation and vacuum sealing drainage in the treatment of hypertrophic scar in non-functional sites after burns

Meng Yanbin, Lei Jin, Zhang Hairui, Hao Zhenming, Bai Peiyi, Duan Peng

2022, 38(3): 251-255. doi: 10.3760/cma.j.cn501120-20201201-00510

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Objective To investigate the clinical effects of in situ perforation of preserved split scar matrix in combination with scalp transplantation and vacuum sealing drainage in the treatment of hypertrophic scar in non-functional sites after burns. Methods A retrospective observational study was used. From June 2017 to June 2019, 33 patients (24 males and 9 females, aged 8-50 years) who met the inclusion criteria with hypertrophic scars in non-functional sites outside the face after burns were treated in General Hospital of TISCO (the Sixth Hospital of Shanxi Medical University). All patients underwent scalp transplantation after perforation of retained split scar matrix in situ (with scar thinning area of 90-500 cm²), and then the vacuum sealing drainage was performed. The hematoma and infection of wounds were observed on the 7^th day after operation. At the same time, the survival rate of skin grafting was observed and calculated. The flatness and thickness of the scar in the operative area were observed in 12 months after operation, and the itching and pain of the patients were recorded. Vancouver Scar Scale was used to score the scar of patients before operation and at 3, 6 and 12 months after operation. The healing time and hair growth of donor site were observed. Data were statistically analyzed with repeated analysis of variance, paired sample t test and bonferroni correction. Results On the 7^th day after operation, local subcutaneous hematoma appeared in the wound of 2 patients, which healed after dressing change; no infection occurred. On the 7^th day after operation, the survival rate of skin grafting of patients was 94.6%-99.0%(96.8±1.2)%. Scar flatness was well, the thickness of scar was not significantly higher than that of normal skin in 12 months after operation, and the symptoms of itching pain of patients disappeared or significantly relieved. Vancouver Scar Scale scores of patients before operation and at 3, 6, and 12 months after operation were 12.1±2.8, 8.5±1.5, 7.6±1.6, 6.7±1.3, respectively, and the scores of 3, 6, and 12 months after operation were all significantly lower than that before operation (with t values of 4.48, 4.06, and 3.97, respectively, P<0.01). All the donor sites of the head healed well in 4-7 days after operation. By 3-6 months after operation, all patients had good hair growth in the donor site and achieved no scar healing. Conclusions The treatment of hypertrophic scar in non-functional sites outside the face after burns by in situ perforation of preserved split scar matrix in combination with scalp transplantation and vacuum sealing drainage can effectively improve the appearance of hypertrophic scar in non-functional areas after burn and reduce its degree of hyperplasia, with scar-free donor site healing.

Effects and mechanism of hydrogen peroxide pretreatment with low molarity on oxidative stress induced apoptosis of mouse bone marrow mesenchymal stem cells

Zhang Shu, Guo Ling, Mi Junwei, Wen Dalin, Sun Jianhui, Zhang Huacai, Du Juan, Cui Li, Jiang Jianxin, Wang Jianmin, Huang Hong

2022, 38(3): 256-265. doi: 10.3760/cma.j.cn501120-20201215-00529

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Objective To investigate the effects and mechanism of hydrogen peroxide (HP) pretreatment with low molarity on oxidative stress induced apoptosis of mouse bone marrow mesenchymal stem cells (BMSCs). Methods The experimental research methods were used. BMSCs were isolated and cultured from two 2-week-old male BALB/c mice by the whole bone marrow culture method. The 3^rd-7^th passages of cells in logarithmic growth phase were used for the experiments after identification. According to the random number table (the same grouping method below), the cells were divided into 0 μmol/L HP group (without HP, the same below), 25 μmol/L HP group, 50 μmol/L HP group, 100 μmol/L HP group, 150 μmol/L HP group, 200 μmol/L HP group, 250 μmol/L HP group, and 300 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respectively. The apoptosis rate was detected by flow cytometry (n=4) after 24 hours of culture. The cells were divided into 0 μmol/L HP group, 25 μmol/L HP group, 50 μmol/L HP group, and 100 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respeclively. After 24 hours of culture, the protein expressions of B-lymphoma-2 (Bcl-2) and Bcl-2-related X protein (Bax) were detected by Western blotting, and the Bcl-2/Bax ratio was calculated (n=3). The cells were divided into 0 μmol/L HP group, 25 μmol/L HP group, 50 μmol/L HP group, 100 μmol/L HP group, 200 μmol/L HP group, and 300 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respectively. After 24 hours of culture, the protein expressions of glycogen synthase kinase-3β (GSK-3β) and phosphorylated GSK-3β (p-GSK-3β) were detected by Western blotting (n=3). The cells were divided into 0 μmol/L HP group, 50 μmol/L HP group, and 300 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respeclively, and HP pretreatment group with 50 μmol/L HP being added in advance for 12 h and then 300 μmol/L HP being added. After 24 hours of culture, the morphology and growth of cells were observed by inverted fluorescence microscopy (non-fluorescent condition) and immunofluorescence method, the apoptosis rate was detected by flow cytometry, the protein expressions of Bcl-2, Bax, cysteine aspartic acid specific protease-3 (caspase-3), caspase-9, cleavage caspase-3, cleavage caspase-9, GSK-3β, and p-GSK-3β were detected by Western blotting, and the Bcl-2/Bax ratio was calculated, with all the number of samples being 3. Data were statistically analyzed with one-way analysis of variance and Bonferroni test. Results After 24 hours of culture, compared with that in 0 μmol/L HP group, the apoptosis rate of cells did not change significantly in 25 μmol/L HP group, 50 μmol/L HP group, or 100 μmol/L HP group (P>0.05) but increased significantly in 150 μmol/L HP group, 200 μmol/L HP group, 250 μmol/L HP group, and 300 μmol/L HP group (P<0.01). After 24 hours of culture, compared with that in 0 μmol/L HP group, the Bcl-2/Bax ratio of cells increased significantly in 25 μmol/L HP group and 50 μmol/L HP group (P<0.05 or P<0.01) but decreased significantly in 100 µmol/L HP group (P<0.05). After 24 hours of culture, compared with those in 0 μmol/L HP group, the protein expression of GSK-3β in cells showed no significant change in 25 μmol/L HP group and 50 μmol/L HP group (P>0.05), the protein expressions of p-GSK-3β in cells significantly increased in 25 μmol/L HP group and 50 μmol/L HP group (P<0.01), the protein expressions of GSK-3β and p-GSK-3β in cells in 100 μmol/L HP group showed no significant change (P>0.05), the protein expressions of GSK-3β in cells in 200 μmol/L HP group and 300 μmol/L HP group were significantly increased (P<0.05). but the protein expression of p-GSK-3β in cells in 200 μmol/L HP group and 300 μmol/L HP group was significantly decreased (P<0.05). After 24 hours of culture, the morphology and growth of cells in 0 μmol/L HP group and 50 μmol/L HP group were similar and normal; in contrast, the cells in 300 µmol/L HP group became smaller and round, with the cell protrusions being shorter or disappeared, the nucleus being cavitated, and the cell abscission being increased significantly; the morphology of most cells in HP pretreatment group was normal, with the shedding of cells being less than that in 300 µmol/L HP group, and the morphology of nucleus being normal. After 24 hours of culture, the protein expression of caspase-9 was similar among the four groups (P>0.05). Compared with that in 0 μmol/L HP group, the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells in 50 μmol/L HP group showed no significant changes (P>0.05), the Bcl-2/Bax ratio of cells in 50 μmol/L HP group increased significantly (P<0.05), the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells in 300 μmol/L HP group were significantly increased (P<0.01), while the Bcl-2/Bax ratio of cells in 300 μmol/L HP group was significantly decreased (P<0.05). Compared with those in 300 μmol/L HP group, the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells were significantly decreased in HP pretreatment group (P<0.05 or P<0.01), while the Bcl-2/Bax ratio of cells was significantly increased in HP pretreatment group (P<0.01). After 24 hours of culture, the protein expressions of GSK-3β and p-GSK-3β of cells in 0 μmol/L HP group, 50 μmol/L HP group, 300 μmol/L HP group, and HP pretreatment group were 1.09±0.14, 0.62±0.17, 1.35±0.21, 0.74±0.34, 0.68±0.03, 0.85±0.08, 0.38±0.10, and 0.54±0.09, respectively. Compared with those in 0 μmol/L HP group, the protein expression of p-GSK-3β of cells was significantly increased in 50 μmol/L HP group (P<0.05) but significantly decreased in 300 μmol/L HP group (P<0.01), while the protein expression of GSK-3β of cells was significantly increased in 300 μmol/L HP group (P<0.05). Compared with those in 300 μmol/L HP group, the protein expression of GSK-3β of cells was significantly decreased in HP pretreatment group (P<0.01), while the protein expression of p-GSK-3β of cells was significantly increased in HP pretreatment group (P<0.01). Conclusions The molarity of 50 μmol/L may be the optimal molarity of HP to pretreat mouse BMSCs, and 50 μmol/L HP pretreatment can antagonize mitochondrial pathway of oxidative stress induced apoptosis by inhibiting the activity of GSK-3β.

Effects of exosomes from human adipose-derived mesenchymal stem cells on pulmonary vascular endothelial cells injury in septic mice and its mechanism

Cai Weixia, Shen Kuo, Cao Tao, Wang Jing, Zhao Ming, Wang Kejia, Zhang Yue, Han Juntao, Hu Dahai, Tao Ke

2022, 38(3): 266-275. doi: 10.3760/cma.j.cn501120-20211020-00362

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Objective To investigate the effects of exosomes from human adipose-derived mesenchymal stem cells (ADSCs) on pulmonary vascular endothelial cells (PMVECs) injury in septic mice and its mechanism. Methods The experimental research method was adopted. The primary ADSCs were isolated and cultured from the discarded fresh adipose tissue of 3 patients (female, 10-25 years old), who were admitted to the First Affiliated Hospital of Air Force Medical University undergoing abdominal surgery, and the cell morphology was observed by inverted phase contrast microscope on the 5^th day. The expressions of CD29, CD34, CD44, CD45, CD73, and CD90 of ADSCs in the third passage were detected by flow cytometry. The third to the fifth passage of ADSCs were collected, and their exosomes from the cell supernatant were obtained by differential ultracentrifugation, and the shape, particle size, and the protein expressions of CD9, CD63, tumor susceptibility gene 101 (TSG101), and β-actin of exosomes were detected, respectively, by transmission electron microscopy, nano-particle tracking analysis and Western blotting. Twenty-four adult male BALB/c mice were adopted and were divided into normal control group, caecal ligation perforation (CLP) alone group, and CLP+ADSC-exosome group with each group of 8 according to random number table (the same grouping method below) and were treated accordingly. At 24 h after operation, tumor necrosis factor (TNF-α) and interleukin 1β (IL-1β) levels of mice serum were detected by enzyme-linked immunosorbent assay, and lung tissue morphology of mice was detected by hematoxylin-eosin and myeloperoxidase staining, and the expression of 8-hydroxy-deoxyguanosine (8-OHdG) of mouse lung cells was detected by immunofluorescence method. Primary PMVECs were obtained from 1-month-old C57 mice regardless gender by tissue block method. The expression of CD31 of PMVECs was detected by immunofluorescence and flow cytometry. The third passage of PMVECs was co-cultured with ADSCs derived exosomes for 12 h, and the phagocytosis of exosomes by PMVECs was detected by PKH26 kit. The third passage of PMVECs were adopted and were divided into blank control group, macrophage supernatant alone group, and macrophage supernatant+ADSC-exosome group, with 3 wells in each group, which were treated accordingly. After 24 h, the content of reactive oxygen species in cells was detected by flow cytometry, the expression of 8-OHdG in cells was detected by immunofluorescence, and Transwell assay was used to determine the permeability of cell monolayer. The number of samples in above were all 3. Data were statistically analyzed with one-way analysis of variance and least significant difference t test. Results The primary ADSCs were isolated and cultured to day 5, growing densely in a spindle shape with a typical swirl-like. The percentages of CD29, CD44, CD73 and CD90 positive cells of ADSCs in the third passage were all >90%, and the percentages of CD34 and CD45 positive cells were <5%. Exosomes derived from ADSCs of the third to fifth passages showed a typical double-cavity disc-like structure with an average particle size of 103 nm, and the protein expressions of CD9, CD63 and TSG101 of exosomes were positive, while the protein expression of β-actin of exosomes was negative. At 24 h after operation, compared with those in normal control group, both the levels of TNF-α and IL-1β of mice serum in CLP alone group were significantly increased (with t values of 28.76 and 29.69, respectively, P<0.01); compared with those in CLP alone group, both the content of TNF-α and IL-1β of mice serum in CLP+ADSC-exosome group was significantly decreased (with t values of 9.90 and 4.76, respectively, P<0.05 or P<0.01). At 24 h after surgery, the pulmonary tissue structure of mice in normal control group was clear and complete without inflammatory cell infiltration; compared with those in normal control group, the pulmonary tissue edema and inflammatory cell infiltration of mice in CLP alone group were more obvious; compared with those in CLP alone group, the pulmonary tissue edema and inflammatory cell infiltration of mice in CLP+ADSC-exosome group were significantly reduced. At 24 h after operation, endothelial cells in lung tissues of mice in 3 groups showed positive expression of CD31; compared with that in normal control group, the fluorescence intensity of 8-OHdG positive cells of the lung tissues of mice in CLP alone group was significantly increased, and compared with that in CLP alone group, the fluorescence intensity of 8-OHdG positive cells in the lung tissues of mice in CLP+ADSC-exosome group was significantly decreased. The PMVECs in the 3^rd passage showed CD31 positive expression by immunofluorescence, and the result of flow cytometry showed that CD31 positive cells accounted for 99.5%. At 12 h after co-culture, ADSC-derived exosomes were successfully phagocytose by PMVECs and entered its cytoplasm. At 12 h after culture of the third passage of PMVECs, compared with that in blank control group, the fluorescence intensity of reactive oxygen species of PMVECs in macrophage supernatant alone group was significantly increased (t=15.73, P<0.01); compared with that in macrophage supernatant alone group, the fluorescence intensity of reactive oxygen species of PMVECs in macrophage supernatant+ADSC-exosome group was significantly decreased (t=4.72, P<0.01). At 12 h after culture of the third passage of PMVECs, and the 8-OHdG positive fluorescence intensity of PMVECs in macrophage supernatant alone group was significantly increased; and compared with that in blank control group, the 8-OHdG positive fluorescence intensity of PMVECs in macrophage+ADSC-exosome supernatant group was between blank control group and macrophage supernatant alone group. At 12 h after culture of the third passage PMVECs, compared with that in blank control group, the permeability of PMVECs monolayer in macrophage supernatant alone group was significantly increased (t=6.34, P<0.01); compared with that in macrophage supernatant alone group, the permeability of PMVECs monolayer cells in macrophage supernatant+ADSC-exosome group was significantly decreased (t=2.93, P<0.05). Conclusions Exosomes derived from ADSCs can ameliorate oxidative damage in mouse lung tissue, decrease the level of reactive oxygen species, 8-OHdG expression, and permeability of PMVECs induced by macrophage supernatant.

Two cases of Vibrio vulnificus primary sepsis

Cheng Dasheng, Ji Shizhao, Wang Guangyi, Zhu Feng, Xiao Shichu, Zhu Shihui

2022, 38(3): 276-280. doi: 10.3760/cma.j.cn501120-20201027-00448

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This article analyzed the medical records of two patients with Vibrio vulnificus primary sepsis who were admitted to the First Affiliated Hospital of Naval Medical University and reviewed the latest literature. On November 6, 2019, a 54-year-old male patient was admitted to the hospital. The patient's lower limbs were red, swollen, and painful with ecchymosis and hemorrhagic bullae after he ate freshwater products. The emergency fasciotomy was performed 3 h after admission, and the multiple organ failure occurred after operation. The patient was given up treatment 24 h after admission. On August 12, 2020, a 73-year-old male patient was admitted to the hospital. He was in shock state on admission and had hemorrhagic bullae on his right lower limb after he ate seafood. At 3 h post admission, he underwent emergency surgical exploration and amputation of right thigh. Six days later, he received negative pressure wound treatment on the stump. On the 13^th day post admission, his families forgo the active treatment and he died 15 d after admission. The two cases were both failed to be diagnosed at the first time, and the disease progressed rapidly. Necrotizing fasciitis and multiple organ failure occurred. After the diagnosis was confirmed, timely fasciotomy and high amputation were performed respectively. The microbiological examinations both reported Vibrio vulnificus. Although the 2 cases were not cured successfully, the course of disease and some indexes of patient with early amputation were better than those of patients with fasciotomy. Vibrio vulnificus is widely distributed and frequently detected in fresh water products. The pathogenic pathway is fuzzy and complex, and it is easy to be misdiagnosed. It is necessary to establish the treatment process of Vibrio vulnificus sepsis. Early and aggressive surgical intervention should be carried out as soon as possible, fasciotomy and debridement should be thorough, and the patients with hemorrhagic bullae should be amputated early. Postoperative comprehensive measures are also important for improving the survival rate of patients.

Research advances on stem cell therapy for diabetic foot wounds

Lin Zhihu, Wang Jun, Liang Zunhong, Pan Yunchuan

2022, 38(3): 281-286. doi: 10.3760/cma.j.cn501120-20210828-00292

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Diabetic foot wound repair is a challenging issue in clinical practice. Due to the influence of multiple factors including the damage and regeneration failure of local tissue, the impaired pathways of wound repairing through blood vessels and nerve nutrition, and disorders of a variety of cellular factors, traditional treatment methods are often difficult to achieve good therapeutic effects. Stem cells are a type of cells with potentials of multidirectional differentiation, which also possess functions such as regulating immunity and paracrine to facilitate the comprehensive wound repair, so they have promising application prospect at present for the treatment of diabetic foot wounds. Because the relevant parameters of stem cell treatment are in the exploratory phase, there were no standardized data. This paper reviews the application of stem cells in the research of diabetic foot wound treatment over the past 6 years, analyzing and summarizing the contents in focused aspects including the types and sources of stem cells, effects of donor age and gender on stem cells, mode of administration, transplantation survival rate and safety, which may provide a reference for further application of stem cells in the clinical treatment of diabetic foot wound.

Research advances of music therapy and its application in the field of burn treatment

Zhang Xiuhang, Zhou Xin, Hong Lei, Gao Xinxin, Hou Zheyu, Fan Xing, Xie Chunhui, Liu Xi, Chen Xinxin, Yu Jia'ao

2022, 38(3): 287-291. doi: 10.3760/cma.j.cn501120-20201217-00533

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Different from other trauma, the scar and pigmentation formed after healing of burn wound not only hinder beauty but also easily lead to a series of sequential psychological problems, such as depression and anxiety. Music therapy, as a supplementary treatment, is widely used in many fields including medical and health care and psychological regulation. However, affected by factors such as medical resources, the awareness and acceptance of music therapy among burn treatment workers in China are still low. Based on the clinical characteristics of burns, this paper matches the applicability of music therapy with it, summarizes the supplementary application of music therapy in the field of burn treatment, expounds this natural science with both science and aesthetics, and puts forward feasible suggestions for its future development.

Research advances of real world study in the field of chronic wound

Chen Lingxi, Jia Chiyu, He Yan

2022, 38(3): 291-295. doi: 10.3760/cma.j.cn501120-20210121-00031

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In recent years, as a powerful supplement to the randomized controlled trial (RCT), real world study (RWS) has received more and more attention. However, in the field of chronic wounds, most of the patients have complex condition, and the strict inclusion and exclusion criteria of RCT were lack of practical application values. The RWS provides data closer to the real medical environment in clinical medical practice, drug and medical device supervision, and health technology evaluation. However, RWS has some problems that need to be resolved, such as inconsistent diagnostic criteria and unclear research endpoints. In addition, RWS in chronic wound research in China seems to have not really started yet, and institutions at all levels need to work together to promote the development of RWS.

Research advances on the application of stem cells in sweat gland regeneration

Zhang Jingjuan, Wang Maoying, Zhao Jie, Jiang Duyin

2022, 38(3): 296-300. doi: 10.3760/cma.j.cn501120-20210123-00033

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Sweat gland is one of the important appendage organs of the skin, which plays an important role in thermoregulation and homeostasis maintenance. Sweat glands are damaged and unable to self-repair after burns, resulting in perspiration disorders eventually. However, current clinical strategies cannot restore the function of the damaged sweat glands effectively. Therefore, it is urgent to seek treatments that can promote the regeneration of sweat glands and restore their normal functions. Stem cells have extensive sources, low immunogenicity, high proliferation capacity, and multi-directional differentiation potential, which have become a focus in the field of regenerative medicine. In recent years, a variety of stem cells have been induced to differentiate into sweat gland-like tissue with certain secretory function, which provides treatment direction for sweat gland regeneration after burns in clinic. This article reviews the recent research advances on the application of stem cells in sweat gland regeneration from the perspectives of the manner by which stem cells transform into sweat gland cells in different environments and their influencing factors.

2022 Vol. 38, No. 3

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