1.The combination of berberine and cinnamon polyphenol can improve glucose metabolism in T2DM rats through Bas-TGR5-GLP-1
Wan LIU ; Fei LIANG ; Tie-quan CAI ; Ying LI ; Le LI ; Shu-cai YANG ; Ying LIU ; Yan ZHAO
Acta Pharmaceutica Sinica 2024;59(1):135-142
Berberine (BBR) is the main pharmacological active ingredient of Coptidis, which has hypoglycemic effect, but its clinical application is limited due to its poor oral bioavailability. Polyphenols, derived from cinnamon, are beneficial for type 2 diabetes mellitus (T2DM). The combination of both may have an additive effect. The aim of this study was to investigate the hypoglycemic effect and mechanism of combined medication in diabetic rats. The modeling rats were randomly divided into 5 groups (berberine group, cinnamon group, combined group, metformin group, diabetic control group) and normal control group. The animal experiments were approved by the Animal Ethics Committee (approval number: HMUIRB2022003). The subjects were given orally, and the control group was given equal volume solvent and body weight was measured weekly. Thirty days after administration, oral glucose tolerance test and insulin sensitivity test were performed, and fasting blood glucose (FBG), glycated serum protein (GSP), and serum insulin (INS) levels were detected; high-throughput sequencing technology was used to detect intestinal microbiota structure; real-time quantitative PCR (RT-qPCR) and Western blot were used to detect G protein-coupled receptor 5 (TGR5) and glucagon-like peptide-1 (GLP-1) expression levels. The results showed that, compared with the diabetic control group, the levels of FBG (
2.Influence of early blood glucose fluctuations after acute multiple injuries on post-traumatic stress disorder
Jingjing WANG ; Wenjia JIANG ; Yanze LI ; Ting XUE ; Ying YE ; Xianliang YAN ; Tie XU ; Rong HUA
Chinese Journal of Emergency Medicine 2024;33(5):623-629
Objective:To investigate the impact of early blood glucose fluctuations after acute multiple injuries on post-traumatic stress disorder (PTSD).Methods:This study was a case-control study. From March 2022 to March 2023, patients with acute multiple injuries who were admitted to the ICU of the Affiliated Hospital of Xuzhou Medical University were selected. According to whether complicated with traumatic brain injury (TBI), the patients were divided into TBI group and non-TBI group. Early post-traumatic blood glucose fluctuations were observed, including stress-induced hyperglycemia (SIH), initial blood glucose value on admission, blood glucose extreme, short-term glycemic variability (GV) and other related indicators. The 72-hour glucose coefficient of variation (Glu-CV) was used to reflect short-term GV. After 1 month, the PTSD checklist for DSM-5 (PCL-5) was used to assess the patient's symptoms of PTSD. The patients were divided into PTSD group and non-PTSD group according to PCL-5 score ≥38. The differences in short-term glucose fluctuations in each groups were compared; the risk factors of PTSD were analyzed by logistic regression; the receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of related indicators on the incidence of PTSD.Results:159 patients with acute multiple injuries were selected and defined as the TBI group ( n=94) and non-TBI group ( n=65). The incidence of PTSD, PCL-5 scale scores, the incidence of SIH and 72 h Glu-CV in the TBI group were significantly higher than the non-TBI group (all P<0.05). The incidence of SIH and 72 h Glu-CV in the PTSD group were significantly higher than the non-PTSD group (both P<0.05). Multivariate logistic regression analysis showed that 72 h Glu-CV ( OR=1.333, 95% CI: 1.028-1.727, P=0.030) was the independent risk factor for PTSD after acute multiple injuries, and the area under the ROC curve was 0.861 (95% CI: 0.789-0.933, P<0.001), the sensitivity was 62.9% and the specificity was 93.5%. Conclusion:Patients with acute multiple injuries with TBI are more likely to have early glucose fluctuations and develop PTSD, and increased short-term glucose variability is the independent risk factor for PTSD after acute multiple injuries.
3.Progress in study of multifunctionality of DPP4 and mechanism of action of related drug targets
Lei WANG ; Zhi-Hui YANG ; Yang ZHENG ; Ying ZHANG ; Tie-Jian ZHAO ; Wei-Sheng LUO ; Tian-Jian LIANG ; Jia-Hui WANG
Chinese Pharmacological Bulletin 2024;40(12):2212-2217
DPP4 is a serine exopeptidase that is immobilized on the cell membrane and plays a crucial regulatory role in various physiological and pathological activities within the human body.In addition to acting as a transcription factor to regulate the tran-scription and expression of downstream target genes,DPP4 also functions as a transcription-independent regulator through pro-tein-protein interactions.In recent studies,DPP4 has been strongly linked to various diseases,and several substances with the potential to target DPP4 have been identified.This paper mainly reviews the multifunctionality of DPP4 in regulating vari-ous aspects of energy metabolism,inflammation,tissue repair and carcinogenesis in the body.It also reviews the screening of in vitro inhibitors of DPP4 and its research progress in regulating chronic liver disease,based on the pathological development process of chronic liver disease.
4.Effects of continuous blood purification on mitochondrial function of mononuclear cells and prognosis of patients with traumatic sepsis
Zhixin LI ; Tie LYU ; Liezhou JIN ; Lyujian CHEN ; Xiaolong XI ; Lijun YING
Chinese Journal of Trauma 2024;40(11):1008-1015
Objective:To investigate the effects of continuous blood purification (CBP) on mitochondrial function of peripheral blood mononuclear cells and clinical prognosis of patients with traumatic sepsis.Methods:A prospective cohort study was used to analyze the clinical data of 90 patients with traumatic sepsis admitted to the Intensive Care Unit of Shaoxing People′s Hospital from January 2023 to June 2024. Based on standard operating procedures (SOP), patients were divided into CBP group and non-CBP group according to whether they received CBP treatment. The mitochondrial DNA (mtDNA) copy number, activity of mitochondrial respiratory chain complex V, levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-10 in the mononuclear cells on ICU admission and at 12, 24 and 48 hours after treatment were compared between the two groups. Acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score on ICU admission and at 48 hours after treatment were detected in the two groups. The length of ICU stay, total length of hospital stay and 28-day mortality after ICU admission were compared between the two groups.Results:A total of 90 patients with traumatic sepsis were included, comprising 56 males and 34 females, aged 18-82 years [51.3(38.7, 70.6)years], with injury severity score (ISS) of 16-54 points [36.2(17.0, 53.6)points]. There were 52 patients in the CBP group and 38 in the non-CBP group. All the patients were followed up for 7-14 days [10.0(8.0, 12.0)days]. On ICU admission, the mtDNA copy number was 638.5±124.0 in the CBP group and 634.7±122.1 in the non-CBP group ( P>0.05). At 12, 24 and 48 hours after treatment, the mtDNA copy number in the CBP group was 564.2±105.6, 415.7±83.5 and 303.7±77.0 respectively, significantly lower than 622.9±120.2, 581.5±113.6, 530.7±97.8 in the non-CBP group ( P<0.05 or 0.01). At 12, 24 and 48 hours after treatment, the mtDNA copy number in both groups continued to decrease compared with that on ICU admission ( P<0.05). On ICU admission, the activity of mitochondrial respiratory chain complex Ⅴ was (74.0±26.0)pg/ml in the CBP group and (72.8±25.3)pg/ml in the non-CBP group ( P>0.05); at 12, 24 and 48 hours after treatment, it was (69.4±24.2)pg/ml, (78.3±26.8)pg/ml and (91.5±33.5)pg/ml respectively in the CBP group, significantly higher than (65.3±23.6)pg/ml, (60.7±19.4)pg/ml and (53.8±16.9)pg/ml in the non-CBP group ( P<0.05 or 0.01); at 12 hours after treatment, it was decreased in both groups compared with that on ICU admission ( P<0.05); at 24 and 48 hours after treatment, it was gradually increased in the CBP group compared with those on ICU admission and at 12 hours after treatment ( P<0.05), while in the non-CBP group, it continued to decrease ( P<0.05). The levels of TNF-α, IL-6 and IL-10 on ICU admission were (51.6±17.1)pg/ml, (174.1±57.3)pg/ml and (67.6±16.2)pg/ml respectively in the CBP group and (49.5±16.7)pg/ml, (177.8±58.7)pg/ml and (65.7±16.6)pg/ml respectively in the non-CBP group ( P>0.05). At 12, 24 and 48 hours after treatment, the levels of TNF-α in the CBP group were (43.6±15.6)pg/ml, (29.4±12.5)pg/ml and (26.2±10.6)pg/ml respectively, the IL-6 levels were (122.4±41.7)pg/ml, (90.6±33.1)pg/ml, (75.6±24.7)pg/ml respectively and the IL-10 levels were (72.6±18.1)pg/ml, (80.7±20.6)pg/ml, (86.2±22.9)pg/ml respectively, which were significantly lower than (48.8±16.2)pg/ml, (46.5±15.5)pg/ml, (40.0±14.2)pg/ml at 12 hours after treatment, (168.4±51.6)pg/ml, (131.5±42.7)pg/ml, (112.7±35.8)pg/ml at 24 hours after treatment, and (78.6±19.3)pg/ml, (91.1±23.8)pg/ml, (99.4±26.6)pg/ml at 48 hours after treatment in the non-CBP group ( P<0.05 or 0.01). At 12, 24 and 48 hours after treatment, the levels of TNF-α and IL-6 in both groups continued to decrease, while the levels of IL-10 continued to increase compared with those on ICU admission ( P<0.05). On ICU admission, the APACHE Ⅱ and SOFA scores were (20.6±10.5)points and (6.2±1.9)points in the CBP group and (21.2±11.2)points and (6.7±2.1)points in the non-CBP group ( P>0.05). At 48 hours after treatment, the APACHE Ⅱ and SOFA scores were (13.5±6.6)points and (2.7±0.6)points in the CBP group, which were significantly lower than (18.3±9.3)points and (5.3±1.5)points in the non-CBP group ( P<0.01). At 48 hours after treatment, the APACHE II and SOFA scores in both groups were significantly decreased compared with those on ICU admission ( P<0.05 or 0.01). The length of ICU stay, total length of hospital stay and 28-day mortality after ICU admission were (13.0±5.7)days, (20.4±8.6)days and 19.2% (10/52) respectively, which were significantly shorter and smaller than (17.6±6.6)days, (26.5±9.4)days and 31.6% (12/38) in the non-CBP group ( P<0.05 or 0.01). Conclusions:CBP treatment may reduce the release of mtDNA by alleviating the mitochondrial damage of the mononuclear cells in patients with traumatic sepsis so that the release of inflammatory factors and cellular apoptosis is reduced, and improve the state of cell energy metabolism and cellular immune function by increasing the activity of mitochondrial respiratory chain complex V in the mononuclear cells, and participate in the reconstruction of immune homeostasis of the body so the inflammatory state and clinical prognosis of the patients are improved.
5.Clinical and genetic characteristics of 3 children with GM1 gangliosidosis and literature review
Xiaoling TIE ; Fengyu CHE ; Ying YANG ; Xiaocong CHEN
Chinese Journal of Neurology 2024;57(10):1136-1143
Objective:To analyze the clinical, genetic, and bioinformatic characteristics of 3 children diagnosed with GM1 gangliosidosis type Ⅰ, and to conduct a literature review.Methods:From January 2020 through December 2022, a detailed examination, encompassing whole-exon sequencing and the evaluation of β-galactosidase enzymatic function, was undertaken for 3 pediatric inpatients at Xi′an Children′s Hospital. Each child presented with distinct clinical features: recurrent seizures, developmental delays, and hypotonia. Concurrently, computational tools MutaBind2 and PyMOL were employed to prognosticate the potential impact of identified genetic mutations.Results:All 3 children experienced severe developmental delay or regression in infancy, accompanied by epilepsy. Serum alkaline phosphatase and aspartate aminotransferase were significantly increased. Furthermore, the serum β-galactosidase activity was 1.59%, 3.47%, 1.96%,respectively. Brain magnetic resonance imaging revealed poor myelination and X-ray examinations demonstrated beak-like changes in the anterior edge of the lumbar spine. All 3 children carried compound heterozygous variants in the GLB1 gene. The c.148T>C variant had not been previously reported, while the c.785G>T, c.1438A>G and c.304C>G variants were only present in 1 case. It was predicted that the mutated protein exhibited reduced binding affinity, with an interrupted hydrogen bond or the formation of a significant steric hindrance with the neighboring residues. Combined with the literature evidence, it was hypothesized that the mutations could potentially impact the overall structure and stability of the GLB protein, leading to a decrease in enzyme activity. Conclusions:The diagnosis and classification of GM1 ganglioside storage disease need to integrate the clinical features, exome sequencing and β-galactosidase activity assay. Bioinformatics analysis is helpful to predict the effect of mutations on protein structure and function.
6.The Effect of Platelet Fibrin Plasma (PFP) on Postoperative Refractory Wounds: Physiologically Concentrated Platelet Plasma in Wound Repair
Lu FAN ; Ying ZHANG ; Xiankun YIN ; Silu CHEN ; Pin WU ; Tianru HUYAN ; Ziyang WANG ; Qun MA ; Hua ZHANG ; Wenhui WANG ; Chunyan GU ; Lu TIE ; Long ZHANG
Tissue Engineering and Regenerative Medicine 2024;21(8):1255-1267
OBJECTIVE:
Surgical wounds that can’t complete primary healing three weeks after surgery are called postoperative refractory wounds. Postoperative refractory wounds would bring great physical and life burdens to the patients and seriously affect their quality of life. To investigate the effect of platelet fibrin plasma (PFP) on postoperative refractory wound healing.APPROACH: The composition of PFP was analyzed using blood routine and blood biochemicals. Clinical data were collected that met the inclusion criteria after treatment with PFP, and the efficacy of PFP was evaluated by wound healing rate and days to healing. Next, growth factor content in PFP, PRP, and PPP was analyzed using ELISA, and PFP-treated cells were applied to investigate the effect of PFP on fibroblast and endothelial cell function.
RESULTS:
PFP component analysis revealed no statistical difference between platelet concentration in PFP and physiological concentration. Clinical statistics showed that PFP treatment was effective in the postoperative refractory wound (four-week wound healing rate [ 90%), significantly better than continuous wound dressing. Meanwhile, our result also proved that PFP treatment significantly enhanced vascularization by upregulated the expression level of CD31 and improved granulation tissue thickness. Activated PFP, PRP, and PPP could continuously release growth factors in vitro and the amount of growth factors released by PRP and PFP was significantly higher than PPP. In vitro studies demonstrated that active PFP could improve cell proliferation, migration, adhesion, and angiogenesis in fibroblasts and endothelial cells.INNOVATION: Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The modified PFP (responsible for accelerating wound healing and enhancing the migration and proliferation of fibroblasts and endothelial cells) was prepared and analyzed for its clinical effectiveness in postoperative refractory wounds.
CONCLUSION
Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The preparation of PFP could significantly reduce the amount of prepared blood, with a good application value for postoperative wounds. PFP can be considered a treatment option, especially for postoperative refractory wounds.
7.The Effect of Platelet Fibrin Plasma (PFP) on Postoperative Refractory Wounds: Physiologically Concentrated Platelet Plasma in Wound Repair
Lu FAN ; Ying ZHANG ; Xiankun YIN ; Silu CHEN ; Pin WU ; Tianru HUYAN ; Ziyang WANG ; Qun MA ; Hua ZHANG ; Wenhui WANG ; Chunyan GU ; Lu TIE ; Long ZHANG
Tissue Engineering and Regenerative Medicine 2024;21(8):1255-1267
OBJECTIVE:
Surgical wounds that can’t complete primary healing three weeks after surgery are called postoperative refractory wounds. Postoperative refractory wounds would bring great physical and life burdens to the patients and seriously affect their quality of life. To investigate the effect of platelet fibrin plasma (PFP) on postoperative refractory wound healing.APPROACH: The composition of PFP was analyzed using blood routine and blood biochemicals. Clinical data were collected that met the inclusion criteria after treatment with PFP, and the efficacy of PFP was evaluated by wound healing rate and days to healing. Next, growth factor content in PFP, PRP, and PPP was analyzed using ELISA, and PFP-treated cells were applied to investigate the effect of PFP on fibroblast and endothelial cell function.
RESULTS:
PFP component analysis revealed no statistical difference between platelet concentration in PFP and physiological concentration. Clinical statistics showed that PFP treatment was effective in the postoperative refractory wound (four-week wound healing rate [ 90%), significantly better than continuous wound dressing. Meanwhile, our result also proved that PFP treatment significantly enhanced vascularization by upregulated the expression level of CD31 and improved granulation tissue thickness. Activated PFP, PRP, and PPP could continuously release growth factors in vitro and the amount of growth factors released by PRP and PFP was significantly higher than PPP. In vitro studies demonstrated that active PFP could improve cell proliferation, migration, adhesion, and angiogenesis in fibroblasts and endothelial cells.INNOVATION: Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The modified PFP (responsible for accelerating wound healing and enhancing the migration and proliferation of fibroblasts and endothelial cells) was prepared and analyzed for its clinical effectiveness in postoperative refractory wounds.
CONCLUSION
Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The preparation of PFP could significantly reduce the amount of prepared blood, with a good application value for postoperative wounds. PFP can be considered a treatment option, especially for postoperative refractory wounds.
8.The Effect of Platelet Fibrin Plasma (PFP) on Postoperative Refractory Wounds: Physiologically Concentrated Platelet Plasma in Wound Repair
Lu FAN ; Ying ZHANG ; Xiankun YIN ; Silu CHEN ; Pin WU ; Tianru HUYAN ; Ziyang WANG ; Qun MA ; Hua ZHANG ; Wenhui WANG ; Chunyan GU ; Lu TIE ; Long ZHANG
Tissue Engineering and Regenerative Medicine 2024;21(8):1255-1267
OBJECTIVE:
Surgical wounds that can’t complete primary healing three weeks after surgery are called postoperative refractory wounds. Postoperative refractory wounds would bring great physical and life burdens to the patients and seriously affect their quality of life. To investigate the effect of platelet fibrin plasma (PFP) on postoperative refractory wound healing.APPROACH: The composition of PFP was analyzed using blood routine and blood biochemicals. Clinical data were collected that met the inclusion criteria after treatment with PFP, and the efficacy of PFP was evaluated by wound healing rate and days to healing. Next, growth factor content in PFP, PRP, and PPP was analyzed using ELISA, and PFP-treated cells were applied to investigate the effect of PFP on fibroblast and endothelial cell function.
RESULTS:
PFP component analysis revealed no statistical difference between platelet concentration in PFP and physiological concentration. Clinical statistics showed that PFP treatment was effective in the postoperative refractory wound (four-week wound healing rate [ 90%), significantly better than continuous wound dressing. Meanwhile, our result also proved that PFP treatment significantly enhanced vascularization by upregulated the expression level of CD31 and improved granulation tissue thickness. Activated PFP, PRP, and PPP could continuously release growth factors in vitro and the amount of growth factors released by PRP and PFP was significantly higher than PPP. In vitro studies demonstrated that active PFP could improve cell proliferation, migration, adhesion, and angiogenesis in fibroblasts and endothelial cells.INNOVATION: Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The modified PFP (responsible for accelerating wound healing and enhancing the migration and proliferation of fibroblasts and endothelial cells) was prepared and analyzed for its clinical effectiveness in postoperative refractory wounds.
CONCLUSION
Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The preparation of PFP could significantly reduce the amount of prepared blood, with a good application value for postoperative wounds. PFP can be considered a treatment option, especially for postoperative refractory wounds.
9.The Effect of Platelet Fibrin Plasma (PFP) on Postoperative Refractory Wounds: Physiologically Concentrated Platelet Plasma in Wound Repair
Lu FAN ; Ying ZHANG ; Xiankun YIN ; Silu CHEN ; Pin WU ; Tianru HUYAN ; Ziyang WANG ; Qun MA ; Hua ZHANG ; Wenhui WANG ; Chunyan GU ; Lu TIE ; Long ZHANG
Tissue Engineering and Regenerative Medicine 2024;21(8):1255-1267
OBJECTIVE:
Surgical wounds that can’t complete primary healing three weeks after surgery are called postoperative refractory wounds. Postoperative refractory wounds would bring great physical and life burdens to the patients and seriously affect their quality of life. To investigate the effect of platelet fibrin plasma (PFP) on postoperative refractory wound healing.APPROACH: The composition of PFP was analyzed using blood routine and blood biochemicals. Clinical data were collected that met the inclusion criteria after treatment with PFP, and the efficacy of PFP was evaluated by wound healing rate and days to healing. Next, growth factor content in PFP, PRP, and PPP was analyzed using ELISA, and PFP-treated cells were applied to investigate the effect of PFP on fibroblast and endothelial cell function.
RESULTS:
PFP component analysis revealed no statistical difference between platelet concentration in PFP and physiological concentration. Clinical statistics showed that PFP treatment was effective in the postoperative refractory wound (four-week wound healing rate [ 90%), significantly better than continuous wound dressing. Meanwhile, our result also proved that PFP treatment significantly enhanced vascularization by upregulated the expression level of CD31 and improved granulation tissue thickness. Activated PFP, PRP, and PPP could continuously release growth factors in vitro and the amount of growth factors released by PRP and PFP was significantly higher than PPP. In vitro studies demonstrated that active PFP could improve cell proliferation, migration, adhesion, and angiogenesis in fibroblasts and endothelial cells.INNOVATION: Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The modified PFP (responsible for accelerating wound healing and enhancing the migration and proliferation of fibroblasts and endothelial cells) was prepared and analyzed for its clinical effectiveness in postoperative refractory wounds.
CONCLUSION
Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The preparation of PFP could significantly reduce the amount of prepared blood, with a good application value for postoperative wounds. PFP can be considered a treatment option, especially for postoperative refractory wounds.
10.The Effect of Platelet Fibrin Plasma (PFP) on Postoperative Refractory Wounds: Physiologically Concentrated Platelet Plasma in Wound Repair
Lu FAN ; Ying ZHANG ; Xiankun YIN ; Silu CHEN ; Pin WU ; Tianru HUYAN ; Ziyang WANG ; Qun MA ; Hua ZHANG ; Wenhui WANG ; Chunyan GU ; Lu TIE ; Long ZHANG
Tissue Engineering and Regenerative Medicine 2024;21(8):1255-1267
OBJECTIVE:
Surgical wounds that can’t complete primary healing three weeks after surgery are called postoperative refractory wounds. Postoperative refractory wounds would bring great physical and life burdens to the patients and seriously affect their quality of life. To investigate the effect of platelet fibrin plasma (PFP) on postoperative refractory wound healing.APPROACH: The composition of PFP was analyzed using blood routine and blood biochemicals. Clinical data were collected that met the inclusion criteria after treatment with PFP, and the efficacy of PFP was evaluated by wound healing rate and days to healing. Next, growth factor content in PFP, PRP, and PPP was analyzed using ELISA, and PFP-treated cells were applied to investigate the effect of PFP on fibroblast and endothelial cell function.
RESULTS:
PFP component analysis revealed no statistical difference between platelet concentration in PFP and physiological concentration. Clinical statistics showed that PFP treatment was effective in the postoperative refractory wound (four-week wound healing rate [ 90%), significantly better than continuous wound dressing. Meanwhile, our result also proved that PFP treatment significantly enhanced vascularization by upregulated the expression level of CD31 and improved granulation tissue thickness. Activated PFP, PRP, and PPP could continuously release growth factors in vitro and the amount of growth factors released by PRP and PFP was significantly higher than PPP. In vitro studies demonstrated that active PFP could improve cell proliferation, migration, adhesion, and angiogenesis in fibroblasts and endothelial cells.INNOVATION: Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The modified PFP (responsible for accelerating wound healing and enhancing the migration and proliferation of fibroblasts and endothelial cells) was prepared and analyzed for its clinical effectiveness in postoperative refractory wounds.
CONCLUSION
Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The preparation of PFP could significantly reduce the amount of prepared blood, with a good application value for postoperative wounds. PFP can be considered a treatment option, especially for postoperative refractory wounds.

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