BACKGROUND:Exosomes play a role in all stages of wound repair,and there is currently a large body of research on exosomes in skin wound repair,which has been shown to have great potential for clinical applications. OBJECTIVE:To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds,in order to promote the clinical translation of exosomes. METHODS:PubMed,clinicaltrials.gov,China National Knowledge Infrastructure,Food and Drug Administration database,and Chinese Clinical Trial Register were searched from inception to March 2023.The English search terms were"exosomes,wound healing,stem cells,chronic wound,immunoregulation,inflammation,skin,therapeutic use,isolation,characterization,infections".The Chinese search terms were"exosomes,wound healing,stem cells,immunomodulation,clinical applications".A total of 79 articles were included for the summary. RESULTS AND CONCLUSION:(1)Exosomes can improve and accelerate wound healing through inflammation regulation,immune protection,angiogenesis,cell proliferation and migration,and collagen remodeling.(2)Exosomes derived from stem cells have mature preparation techniques and related mechanism research,which is currently the mainstream research direction.Non-stem cell-derived exosomes have the advantages of convenience,economy,and easy production,and can be used as a supplement for clinical applications.(3)The clinical application of exosomes is still in its infancy,but has great potential for application.Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research.(4)The clinical translation of exosomes faces many challenges,such as low yield,high heterogeneity,lack of unified standards for isolation,purification,and quality control,and difficulties in storage.

Objective To explore the effect and mechanism of Chaihu Longgu Muli Decoction (柴胡龙骨牡蛎汤, CHLGMLD) in rats with temporal lobe epilepsy (TLE). Methods A total of 80 Sprague-Dawley (SD) male rats were randomized into control (CON), model (MOD), carbamazepine (CBZ, 0.1 g/kg), CHLGMLD low dose (CHLGMLD-L, 12.5 g/kg), and high dose (CHLGMLD-H, 25 g/kg) groups, with 16 rats in each group. TLE rat models were established in the four groups with the use of lithium-pilocarpine except for the CON group. After the successful establishment of TLE models, all drugs were administered through gavage, and distilled water was given to rats in the CON and MOD groups for four weeks. The frequency and duration of seizures before and after treatment were recorded for the evaluation of the alleviation degree. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-146a-3p and miR-146a-5p. The expression levels of toll-like receptor 4 (TLR4), interleukin-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), TAK1-binding protein (TAB), nuclear factor-kappa B (NF-κB), and interleukin-1 beta (IL-1β) in hippocampus were tested by immunofluorescence assay. Correlation analysis between the above factors and expressions of miR-146a-3p and miR-146a-5p were performed separately. Results CHLGMLD decreased the frequency (P < 0.05) and duration (P < 0.01) of seizures in rats. CHLGMLD down-regulated the expression levels of miR-146a-5p and miR-146a-3p (P < 0.05), and inhibited the expression levels of TLR4, IRAK1, TRAF6, TAB, NF-κB, and IL-1β (P < 0.01). The correlation analysis revealed that the expression levels of TLR4, IRAK1, TRAF6, TAB, NF-κB, and IL-1β were positively correlated with the expression levels of miR-146a-3p and miR-146a-5p detected by qRT-PCR, respectively (P < 0.01). Conclusion CHLGMLD can inhibite the TLR4 signaling pathway by lowering the expression levels of miR-146a-3p and miR-146a-5p to alleviate hippocampal dentate gyrus inflammation in TLE rats, thus relieving seizures.

Objective:To investigate the epidemiological characteristics of lower extremity deep vein thrombosis (DVT) in patients with femoral fracture.Methods:Retrospectively analyzed were the data of 2,571 patients with femoral fracture who had been treated at the Third Hospital of Hebei Medical University from January 2019 to December 2019. There were 1,079 males and 1,492 females, aged from 14 to 96 years (average, 67.1 years). There were 1,158 femoral neck fractures, 951 femoral intertrochanteric fractures, 309 femoral shaft fractures, and 153 femoral condylar fractures. 2,414 patients were treated surgically while 157 patients non-surgically. Color Doppler ultrasonography of both lower extremities was performed to determine the occurrence of DVT before operation and every week after operation for patients undergoing surgical treatment, and within 48 hours after admission and every week during hospitalization for those undergoing non-surgical treatment. The incidence and location of DVT were recorded for different femoral fractures.Results:The incidence of DVT in this cohort was 35.5%(913/2,517), that of proximal DVT 5.3%(135/2,571), and that of distal DVT 30.3% (778/2,571). In patients with femoral neck fracture, femoral intertrochanteric fracture, femoral shaft fracture and femoral condylar fracture, the incidence of DVT was respectively 28.8% (334/1,158), 44.7% (425/951), 30.7% (95/309) and 38.6% (59/153), the incidence of proximal DVT was respectively 2.7% (31/1,158), 5.6%(53/951), 9.7% (30/309) and 13.7% (21/153), and the incidence of distal DVT was respectively 26.2% (303/1,158), 39.1% (372/951), 21.0% (65/309) and 24.8%(38/153). The incidence of DVT in the femoral vein and above, popliteal vein, tibiofibular vein and intermuscular vein in this cohort was respectively 2.3%(60/2,571), 2.9%(75/2,571), 6.4%(165/2,571) and 23.8%(613/2,571).Conclusions:The incidence of DVT may be high in patients with femoral fracture, and the proximal DVT with a high risk of pulmonary embolism may occur more in patients with femoral condylar fracture.

Objective:To determine the median effective concentration (EC 50) of ropivacaine producing sensory-motor separation when used for femoral nerve block performed under ultrasound guidance. Methods:American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients of both sexes, aged 18-64 yr, with body mass index of 18-30 kg/m 2, scheduled for elective arthroscopic knee surgery under general anesthesia, were enrolled in this study. Femoral nerve block was performed under ultrasound guidance.After successful location, ropivacaine 22 ml was injected with the initial concentration of 0.50%, and the ratio between the two consecutive concentrations was 1.1.The EC 50 of ropivacaine was determined by up-and-down sequential method.The positive response was considered as sensory block without motor block.The negative response was considered as sensory and motor block.When a negative response was found, the concentration was decreased in the next patient.When a positive response occurred, the concentration was increased in the next patient.Probit analysis was used to calculate the EC 50 and 95% confidence interval of ropivacaine producing sensory-motor separation when used for femoral nerve block which was performed under ultrasound guidance. Results:The EC 50 of ropivacaine producing sensory-motor separation was 0.186%, and the 95% confidence interval was 0.155%-0.205% when used for ultrasound-guided femoral nerve block. Conclusion:The EC 50 of ropivacaine producing sensory-motor separation is 0.186% when used for femoral nerve block performed under ultrasound guidance.

Objective:To investigate the effect of vagus nerve stimulation (VNS) on serum cytokines and neurotransmitters in epilepsy patients with depression.Methods:From March 2015 to 2018, 13 patients with epilepsy combined with depression undergoing VNS surgery in Brain Hospital of Hunan Province were selected as the research objects. The surgical efficacy, depression degree, serum cytokines and neurotransmitter changes before operation, 6 months and 12 months after operation were compared.Results:The effective rate of epilepsy treatment at 6 and 12 months after VNS were 61.5%(8/13) and 76.9%(10/13), respectively. After 6 months and 12 months, Hamiton Depression scale (HAMD) and self-rating depression scale (SDS) scores were significantly lower than those before operation ( P<0.05 or P<0.01). At 6 months after operation, serum 5-hydroxytryptamine (5-HT) level was significantly higher than that before operation, while serum interleukin (IL)-1α, IL-6 and tumor necrosis factor α (TNF- α) were significantly lower than those before operation ( P<0.05 or P<0.01). At 12 months after operation, 5-HT and dopamine (DA) were significantly increased, while IL-1 α, IL-2, IL-6 and TNF -α were significantly decreased ( P<0.05 or P<0.01). Conclusions:VNS may can improve epilepsy and depression by regulating the level of neurotransmitter and serum cytokines.

Background Interleukin-6 (IL-6) is a pleiotropic cytokine involving in inflammation and wound healing.Previous report found that IL-6 increases phosphorylated STAT3 (p-STAT3) level and promotes corneal epithelial wound healing by stimulating migration.However,the essential role of IL-6 in corneal epithelial wound healing and the expression changes in diabetic mellitus remains unknown.Objective This study was to explore the roles of IL-6 in corneal epithelial proliferation and wound healing in both normal and diabetic mice.Methods Fifty-two normal C57BL/6 mice were randomized into normal control group (32 mice) and diabetic group (20 mice).Type 1 diabetic mellitus was induced by intraperitoneal injections of 50 mg/kg streptozotocin once per day for consecutive 5 days in the mice of the diabetic group.Whole corneal epithelium was scraped in all mice,and the corneal epithelial defect area was examined by fluorescein staining in 24,48 and 72 hours after corneal epithelium removal.Recombinant mouse IL-6 or anti-IL-6 blocking antibody of 5 μl were subconjunctivally injected according to the grouping and contrasted with PBS injection group or isotype control antibody group,respectively.TKE2 cells,a mouse corneal epithelial stem/progenitor cell line,were trypsinized and incubated in the KSFM with different concentrations of IL-6 or without IL-6,and colony formation efficency (CFE) was examined by crystal violet staining.The expressions of △NP63 and Ki67,specific makers of stem cells,were detected by immunofluorescine technology.The expressions of △NP63,Ki67 and p-STAT3 proteins were assayed in the cells by Western blot,respectively.The expression of IL-6 mRNA and protein in the regenerated corneal epithelium was detected by real time quantitative PCR and ELISA.The use and care of the mice complied with the Statement of Association for Research in Vision and Ophthalmology.Results The percentage of residual corneal epithelium defect area with initial detect area was gradually shrinked over time after PBS and IL-6 injection in both normal control mice and diabetic mice,and the percentage of residual corneal epithelium defect area was significantly reduced in the IL-6 injected group compared with the PBS injected group (normal control group:Fgroup =19.982,P ＜ 0.01;Ftime =589.350,P ＜ 0.01;Diabetic group:Fgroup =25.411,P＜0.01;Ftime =334.807,P＜0.01).The CFE was (13.23± 1.12)％,(15.87± 1.30)％,(21.69±1.62)％,(25.33±1.28)％ and (18.67±1.54)％ in the blank control group and 10,20,50,100 ng/ml IL-6-treated groups,respectively,showing a gradual increase of CFE dependent upon IL-6 concetrations (F =35.547,P＜0.01).The expressions of △NP63,Ki67,p-STAT3 proteins in the cells were gradually increased over time after 50 ng/ml IL-6 treated for 5,10,15,30 and 60 minutes,and the relative expression level of the cytokines was significnatly higher in the IL-6 cultured groups than that without IL-6 culture group (all at P＜0.05).The relative expression of IL-6 mRNA in the regenerated corneal epithelilum was 0.45±0.21 and 1.00±0.16 in the diabetic group and normal control group,respectively,and compared with the normal control group,the expression of IL-6 mRNA reduced by 56％ (t=3.42,P=0.03).The content of IL-6 protein in regenerated corneal epithelium of the diabetic group was (257±12) ng/μl,which was significantly lower than (323 ± 17) ng/μl of the normal control group (t =5.60,P＜0.01).Conclusions IL-6 promotes the proliferation and regeneration of corneal limbal stem cells to repair defected corneal epithelium by activating STAT3 signaling pathway in both normal and diabetic mice,while the blocking of endogenous IL-6 impairs the corneal epithelial cell activation and wound healing.

Objective: To investigate the role of "Hong′s single-stitch duct to mucosa pancreaticojejunostomy(HSDMP)" in laparoscopic pancreaticoduodenectomy (LPD). Methods: The clinical data including perioperative and short-term outcomes of 51 cases of LPD with HSDMP which performed in Zhejiang Provincial People′s Hospital(33 cases) and Frist Clinical Hospital of Jilin University(18 cases) between April and October 2016 were reviewed retrospectively. There were 31 male patients and 20 female patients. The mean age was(59±11)years. Body mass index (BMI) was 18 to 28 kg/m² and the average BMI was (23.2±4.4)kg/m². Preoperative diagnosis: 18 cases with pancreatic mass, 26 cases with peri-ampullary tumor, 3 cases with intra-ductal papillary mucinous neoplasms, 2 cases with duodenal carcinoma, 2 cases with serous cystadenoma. Results: Fifty-one patients accepted LPD using HSDMP. One patient underwent LPD combined with resection of superior mesentery vein. The mean operation time was (307±69)minutes, the mean diameter of pancreatic duct for reconstruction was (3.1±1.1)mm.The mean operation time for HSDMP was (34±5) minutes, the estimated blood loss was (170±127)ml. Twelve cases(23.5%) had pancreatic fistula according to International Study Group definition, including 9 cases(17.6%) of grade A and 3 cases (5.9%) of grade B. Five cases(9.8%) had delayed gastric empty, 5 cases(9.8%) had bile leakage and 2 cases(3.9%) had pulmonary infection postoperative.All these complications were treated by non-surgical strategies. One patient(2.0%) suffered from postoperative intra-abdominal bleeding and recovered after reoperation. Pathologic results showed pancreatic ductal adenocarcinomas in 20 cases(39.2%), non-pancreatic original peri-ampullary tumors in 23 cases(45.1%), intra-ductal papillary mucinous neoplasms in 3 cases(5.9%), duodenal carcinoma in 2 cases(3.9%), serous cystadenoma in 2 cases(3.9%) and neuroendocrine tumors in one case(2.0%). Conclusions HSDMP could not only reduce the incidence of clinical pancreatic fistula, but also save operation time. It is a feasible and safe method for pancreaticojejunostomy.

Objective To investigate the value of ADC histogram of tumor volume measurement in the diagnosis of prostate cancer,and to screen out the best diagnostic parameter value.Methods 31 cases of prostate cancer and 35 cases of benign prostatic hyperplasia confirmed by biopsy or surgical pathology were analyzed retrospectively.DWI examination was performed on all patients before treatment,and b value of 0 and 1500 s/mm2 was selected.The total tumor ADC histogram parameters were measured respectively,including the average value of ADC (ADCmean ),the median ADC (ADCmedian ),the tenth percentile ADC (ADC10th),the twenty-fifth percentile ADC (ADC25th), the fiftieth percentile ADC (ADC50th),the seventy-fifth percentile ADC (ADC75th),the ninetieth percentile ADC (ADC90th), skewness and kurtosis.The histogram parameters of the two groups of patinents and their diagnostic efficacy were analyzed and compared.Results ADCmean ,ADCmedian ,ADC10th,ADC25th,ADC50th,ADC75th and ADC90th in the prostate cancer group were statistically lower than those of benign prostatic hyperplasia group (P <0.01),and there was no significant difference in the skewness and kurtosis between the two groups of diseases (P > 0.05 ).ADCmean ,ADCmedian ,ADC10th,ADC25th,ADC50th,ADC75th and ADC90th diagnosing prostate cancer in the area under ROC curves (AUC)were more than 0.78.ADC10th had the best diagnostic efficacy and its AUC was 0.82, with the optimal cut-off value for 0.27 × 10 -3 mm2/s,with sensitivity and specificity for 78.4％ and 83.3％.Conclusion The ADC histogram of the total tumor volume measurement is of great value in the diagnosis of prostate cancer,among which ADC10th is the most effective parameter.It can accurately distinguish between prostate cancer and prostatic hyperplasia nodules.

Inhibition of NEDD8 activating enzyme (NAE),the rate limiting enzyme in Neddylation,can suppress the activity of ubiquitin-proteasome system (UPS) pathway and decrease degradations of related proteins,resulting in cell apoptosis.Compared with the proteasome inhibitors,NAE inhibitors can interfere with cellular homeostasis with more specificity.With the rapid development of the research on NAE,a variety of NAE inhibitors have been reported.According to the structure characteristics,NAE inhibitors can be divided into the AMP analogues,double flavonoids deoxidization duckbill alkali ketone derivatives and metal rhodium complex classes,etc.The process of ubiquitinated modified Neddylation,NAE and physiological role of tumor has been introduced in this paper,and the latest progress of NAE inhibitors also has been summarized.