OBJECTIVE To investigate the effects of baicalin （BC） on insulin resistance in rats with gestational diabetes mellitus （GDM） and its underlying mechanism based on the adenosine monophosphate-activated protein kinase （AMPK）/suppressor of variegation 3-9 homolog 1 （SUV39H1）/histone H3 lysine 9 trimethylation （H3K9me3） axis. METHODS A GDM rat model was established by a combination of a high-fat diet and streptozotocin injection. The successfully modeled rats were divided into the GDM group， BC low-dose group， BC high-dose group， and high-dose of BC+AMPK inhibitor （Compound C） group， with 10 rats in each group. Another 10 pregnant rats fed a normal diet served as the control group. Rats in each group were given corresponding drugs/normal saline intragastrically and/or intraperitoneally， once daily for 2 consecutive weeks. After the last administration， the levels of fasting blood glucose （FBG）， pancreatic function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]， blood lipid indexes （total cholesterol， triglyceride， low-density lipoprotein cholesterol）， liver function indexes （alanine transferase， aspartate transferase， alkaline phosphatase）， inflammatory indicators （C-reactive protein， interleukin-1β， interleukin-6）， metabolic regulatory protein [complement-C1q/tumor necrosis factor-related protein 3 （CTRP3）]， insulin sensitivity related factors [glucose transporter 4 （GLUT4）， adiponectin]， and oxidative stress indicators [superoxide dismutase （SOD）， catalase （CAT）， malondialdehyde （MDA）] were measured. Pathological changes in liver tissue were observed， and the expressions of proteins related to the AMPK/SUV39H1/H3K9me3 axis in liver tissue were detected. RESULTS Compared with the GDM group， rats in the BC low- and high-dose groups showed varying degrees of improvement in pathological changes such as disordered cell arrangement， vacuolar degeneration， lipid deposition， and inflammatory cell infiltration in liver tissue. Their FBG and FINS levels， HOMA-IR， the levels of blood lipid indexes， liver function indexes， inflammatory indicators and MDA， and the expressions of SUV39H1 and H3K9me3 were significantly decreased or down-regulated， while metabolic regulatory protein， insulin sensitivity-related factors and AMPK protein phosphorylation levels were significantly increased （ P ＜0.05）. The improvement was more significant in the BC high-dose group （ P ＜0.05）. Compound C could significantly reverse the ameliorative effects of high-dose BC on the above quantitative indicators （ P ＜0.05）. CONCLUSIONS BC can significantly reduce oxidative stress and inflammatory responses， increase serum levels of CTRP3， GLUT4 and adiponectin， thereby improving insulin resistance in GDM rats. These effects may be related to the activation of AMPK and inhibition of SUV39H1-mediated H3K9me3 modification.

Based on the core collection retrieval of the Web of Science database,researches related to the medicinal field of plant-derived vesicles(PDVs)were retrieved.The research hotspots and their changes in the pharmaceutical field of PDVs are visually analyzed by using bibliometric software VOSviewer and CiteSpace.A detailed discussion is held around the author,institution,country,key research hotspots and annual develop-ment hotspots,revealing the current research status of PDVs in the pharmaceutical field and predicting future trends,which provides valuable perspectives for researchers to understand the current research status of PDVs in the pharmaceutical field and discover possible unexplored areas in this field.

Objective To explore the role and potential mechanism of Astragali Radix-derived extracelluar vesicles(EVs)-like particles(AR-EVLP)in diabetic wound healing,providing a novel therapeutic drug mode and theoretical basis for traditional Chinese medicine in treating diabetic skin ulcers.Methods AR-EVLP was extracted using ultracentrifugation.Untargeted metabolomics was used to analyze the potential active components of AR-EVLP,and the main active substances in AR-EVLP were identified by comparison with the Herb database.The targets of the active components were obtained through the Swiss Target Prediction database and the TCMSP database.Targets related to diabetic wound healing were obtained from the GeneCards database.Key targets were identified by intersecting drug targets and disease targets.GO functional annotation and KEGG pathway enrichment analysis were performed using the DAVID database.Based on the pathway enrichment results,a"drug components-targets-pathways"diagram was constructed to identify core targets.Molecular docking and visualization were performed using Autodock and PyMOL software.Results Formononetin was identified as the main active component in AR-EVLP,with 66 key targets related to diabetes and wound healing,including 15 key node proteins such as SRC,CASP3 and JUN.GO functional enrichment analysis suggested that formononetin can regulate biological processes such as protein phosphorylation and gene expression.KEGG pathway enrichment analysis indicated potential involvement in multiple signaling pathways,including VEGF and TNF.Seven targets,including PIK3CA,JUN and MAPK14,were identified as core targets for formononetin.Molecular docking showed that formononetin had the strongest binding affinity with MAPK14.Conclusion AR-EVLP may be a potential effective drug mode for the treatment of diabetic wound healing.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Objective·To explore the efficacy and safety of compound amino acid capsules in the treatment of malnutrition and calcium and phosphorus metabolism disorders in maintenance hemodialysis patients.Methods·In this prospective,randomized,controlled,single-center study,forty maintenance hemodialysis patients from Renji Hospital,Shanghai Jiao Tong University School of Medicine were randomly divided into two groups,the treatment group(n=21)and the control group(n=19).The treatment group was given oral compound amino acid capsules on the basis of regular hemodialysis treatment,while the control group received no special nutritional intervention.Serum albumin,prealbumin,hemoglobin,ferritin,calcium,phosphorus,1,25-(OH)2-D3 and intact parathyroid hormone levels were analyzed every 3 months,and the incidence of adverse events including death,cardio-cerebrovascular accidents and vascular access failure was recorded.The total follow-up period was 9 months.Results·Serum albumin and prealbumin in the treatment group at 6-month and 9-month were significantly higher than the baseline parameters(albumin,t=3.574,5.599,both P<0.05;prealbumin,t/Z=-2.485,2.921,both P<0.05).Albumin in the control group increased at 9-month with a lower amplification compared to the treatment group(t=3.877,P=0.001),while the difference of prealbumin showed no statistical significance during follow-up.Hemoglobin and serum ferritin in the treatment group started to increase at 3-month(hemoglobin,t=2.192;ferritin,t=2.994;both P<0.05).Phosphorus in treatment group decreased at 3-month and 9-month(t/Z=-2.743,-2.103,both P<0.05),while phosphorus in the control group remained relatively stable during the first 6 months and increased at 9-month(Z=-2.178,P=0.029).Calcium and 1,25-(OH)2-D3 in the treatment group at 3-month and 6-month were significantly higher than the baseline parameters(calcium,t=4.581,4.922,both P=0.000;1,25-(OH)2-D3 t/Z=4.504,-2.374,both P<0.05),while the increase in blood calcium in the control group was significantly smaller than that in the treatment group during the same period.1,25-(OH)2-D3 in the control group showed no significant improvement.There was no significant difference in intact parathyroid hormone level,incidence of adverse events and other laboratory examination results between the two groups.Conclusion·Compound amino acid capsules can ameliorate the nutrition status and regulate calcium and phosphorus metabolism effectively and safely in maintenance hemodialysis patients.

【Objective】 To investigate the protective effects of aflexible sleeve penile protection device on reducing postoperative pain and wound edema in patients after circumcision. 【Methods】 A total of 54 patients who underwent circumcision at Yan’an Branch of Peking University Third Hospital during Feb.1 and May 31, 2023 were enrolled.The patients were randomly divided into the experimental group and control group, with 27 patients in either groups.Patients in the experimental group were treated with a flexible sleeve penis protection device after surgery, and patients in the control group were treated with traditional gauze bandage after surgery.Postoperative pain, wound edema and complications were compared between the two groups. 【Results】 In terms of pain, the visual analogue scale of the experimental group was significantly lower at 6 hours [(1.7±0.9) vs.(3.3±1.9), P<0.001] and 2 days [(2.0±1.3) vs.(3.3±1.3), P<0.001] after surgery than that of the control group, but there were no statistically significant differences between the two groups on the 4th and 7th postoperative days (P>0.05).In terms of edema, the edema score of the experimental group was significantly lower than that of the control group on the 2nd postoperative day [(2.0±1.0) vs.(4.0±0.8), P<0.001] , the 4th postoperative day [(1.5±1.2) vs.(2.6±0.9), P<0.001] , and the 7th postoperative day [(0.9±1.3) vs.(2.3±1.5), P<0.001] .There was no statistically significant difference in the incidence of complications between the two groups (P>0.05). 【Conclusion】 The flexible sleeve penile protection device has significant effects of reducing early postoperative pain and reducing edema in patients undergoing circumcision.

Objective:To investigate the effect of miR-199a on interstitial transdifferentiation (EMT) of human renal tubular epithelial cells stimulated by high glucose.Methods:Human renal tubular epithelial cells were cultured in vitro and divided into low glycemic group (LG), high osmotic group (HM) and high glycemic group (HG) according to different glucose concentrations. They were divided into miR-199a inhibition group (miR-199ai group), negative control group (miR-INC group) and liposome group (Mock group) according to whether they were transfected with miR-199a inhibitors (miR199ai). They were divided into si-hypoxia-inducible factor-1α (si-HIF-1α) group, miR-199ai group, miR-199ai+ si-HIF-1α group and negative control group (NC group) according to whether they converted to si-HIF-1α and miR-199ai. The expressions of miR-199a, HIF-1α, fibronectin (FN) and α-smooth muscle actin (α-SMA) in different groups of cells were detected by real-time quantitative fluorescent polymerase chain reaction (qRT-PCR) and Western blot. Dual luciferase target assay was used to verify the targeting relationship between miR-199a and HIF-1α gene.Results:The mRNA expression level of miR-199a in the HG group was significantly lower than that in the LG group and the HM group (all P<0.01), and the mRNA and protein expression levels of HIF-1α, FN and α-SMA in Hg group were significantly higher than those in LG group and HM group (all P<0.01). The mRNA and protein expression levels of HIF-1α, FN and α-SMA in the miR-199ai group were significantly higher than those in the miR-iNC group and the Mock group (all P<0.01). Target gene prediction by TargetScan and miRanda showed that miR-199a could target the 3′-untranslated region(3′-UTR) that binds HIF-1α. Dual luciferase reported results: Inhibition of miR-199a resulted in a significant increase in luciferase activity ( P<0.01), but there was no significant change in luciferase activity after 3 ′-UTR mutation of HIF-1α ( P>0.05). After transfection with si-HIF-1α, the mRNA and protein expression levels of HIF-1α, FN and α-SMA in si-HIF-1α group were significantly lower than those in NC group (all P<0.05). After transfection with miR-199ai, the mRNA and protein expression levels of HIF-1α, FN and α-SMA in miR-199ai group were significantly higher than those in NC group (all P<0.05). However, when co-transfected with si-HIF-1α and miR-199ai, the expression levels of mRNA and protein in miR-199AI group were significantly higher than those in NC group (all P<0.05). The mRNA and protein expression changes of HIF-1α, FN and α-SMA induced by transfection of si-HIF-1α or miR-199ai alone can be recovered. Conclusions:miR-199a can alleviate hyperglycemia-induced EMT in human renal tubular epithelial cells through targeted regulation of HIF-1α.

Objective:To find the epidemiological characteristics of nosocomial infection in burn patients, to establish a risk prediction model for nosocomial infection in burn patients based on the screened independent risk factors of the infection, and to analyze its predictive value.Methods:A retrospective case series study was conducted. From May 2016 to December 2019, 3 475 burn patients who were admitted to the Department of Burns of Affiliated Hospital of Jiangnan University met the inclusion criteria, including 2 290 males and 1 185 females, aged from 1 to 94 years. The incidence of nosocomial infection, the detection site and specific composition of pathogenic bacteria were counted. The patients were randomly divided into training group (2 434 cases) and verification group (1 041 cases) in R 4.1.3 statistic software with a ratio of about 7∶3. Factors including gender, age, total burn area, combination of full-thickness burn/inhalation injury/shock/diabetes on admission, admission to intensive care unit (ICU), status of central venous catheterization/endotracheal intubation/urethral catheter indwelling/surgery, nosocomial infection status, days of antibiotic use, and days of hospital stay of patients were compared between the two groups. According to the occurrence of nosocomial infection, the patients were divided into nosocomial infection group (102 cases) and non-nosocomial infection group (3 373 cases), and in addition to the aforementioned data, non-nosocomial infection related data, the season of admission and types of antibiotics used were compared between the two groups. The above-mentioned data were statistically analyzed with one-way analysis of independent sample t test, chi-square test, and Mann-Whitney U test, and the indicators with statistically significant differences between nosocomial infection group and non-nosocomial infection group were included as variables in multivariate logistic regression analysis to screen independent risk factors for the development of nosocomial infection in 3 475 burn patients. On the basis of independent risk factors and important clinical characteristics, a nomogram prediction model was constructed for the risk of developing nosocomial infection of burn patients in training group. In both training group and verification group, receiver operating characteristic (ROC) curves for prediction of nosocomial infection by the prediction model were plotted, and the area under the ROC curve was calculated; calibration curves were plotted to evaluate the conformity between the predicted results of the prediction model and the actual situation; clinical decision curves were plotted to evaluate the clinical utility of the prediction model. Results:The incidence of nosocomial infection of patients included in this study was 2.94% (102/3 475); pathogens were detected from 212 specimens, mainly wound (78 cases, accounting for 36.79%) and blood (64 cases, accounting for 30.19%) specimens; 250 strains of pathogenic bacteria were detected, mainly gram-negative bacteria (153 strains, accounting for 61.20%). All clinical characteristics of patients between training group and verification group were similar ( P>0.05). There were statistically significant differences between patients in nosocomial infection group and non-nosocomial infection group in the aspects of age, total burn area, days of antibiotic use, antibiotic use type, days of hospital stay, combination of full-thickness burn, combination of inhalation injury, combination of shock, ICU admission status, central venous catheterization status, endotracheal intubation status, urethral catheter indwelling status, surgery status (with Z values of 4.41, 14.95, 15.70, 650.32, and 13.73, χ2 values of 151.09, 508.30, 771.20, 955.79, 522.67, 967.40, 732.11, and 225.35, respectively, P<0.01). ICU admission, endotracheal intubation, urethral catheter indwelling, and days of hospital stay were independent risk factors for developing nosocomial infection by 3 475 burn patients (with odds ratios of 5.99, 3.39, 9.32, and 6.21, 95% confidence intervals of 2.25-15.99, 1.56-7.39, 2.77-31.31, and 2.48-15.92, respectively, P<0.01). In training group and verification group, the area under ROC curves of the nosocomial infection prediction model based on independent risk factors, total burn area, and central vein catheterization were both 0.97 (with both 95% confidence intervals being 0.95-0.99); the calibration curve analysis showed that the prediction results of the prediction model were in good agreement with the actual situation; the clinical decision curve analysis showed that the prediction model had good clinical utility. Conclusions:The nosocomial infection in burn patients is mainly caused by gram-negative bacteria, with wound as the main infection site, and the independent risk factors including ICU admission, endotracheal intubation, urethral catheter indwelling, and days of hospital stay. Based on independent risk factors and important clinical features, the risk prediction model for nosocomial infection has a good ability to predict nosocomial infection in burn patients.

Objective:To summarise the advantages and disadvantages of applying the method of retrograde replantation with an operative position of foot stepping and knee bending for replantation of rotational avulsed and fractured great toes.Methods:From January 2016 to June 2021, 11 rotational avulsed and fractured great toes were replanted with the method of retrograde replantation in an operative position of foot stepping and knee bending. Of the 11 patients, 10 were males and 1 was female, aged 18 to 50 years old with an average of 32 years old. Causes of injury: 5 of driving belt, 4 of machinery crush and 2 of car accident. Injury sites: 4 on left great toes and 7 on right great toes. All of the injuries were with fracture and exposure of proximal tendons of flexor and extensor. Seven patients had the follow-up reviews by outpatient clinic visiting, 2 over mobile phone and 2 via WeChat.Results:After surgery, 9 great toes completely survived and 2 great toes had necrosis. The survival rate of toe replantation was 81.8%(9/11). The operation time was 2 to 3 hours, with an average of 2.5 hours. Postoperative X-ray film showed that 8 to 12 weeks after the operation, the fracture and joint fusion were healed at first stage in the survived toes. All patients were entered in follow-up for 3 to 18 months with 10.5 months in average. The survived great toes were plump and the toenail grown well. At the final follow-up, the static TPD at the toes was 8-12 mm, with an average of 10 mm. There was no effect shown on either walking or running.Conclusion:The retrograde replantation method with an operative position of foot stepping and knee bending for great toe replantation has the characteristics of a good field of view and convenient in operation under microscope, a short operation time, and a high survival rate of replantation.

ObjectiveTo assess the curative effects of Fangji Huangqi detumescence prescription （FHDP） on synovitis and polarization of synovial macrophages of knee osteoarthritis （KOA） model in rats induced by Hulth method. MethodThirty-six rats were randomly divided into sham operation group， model group， high-dose， medium-dose， and low-dose （29.16， 14.58， and 7.29 g·kg^-1） FHDP groups， and loxoprofen sodium （16.2 mg·kg^-1） group. KOA model in rats was induced by modified Hulth method. Six weeks after the operation， rats were given high， medium， and low concentrations of FHDP， normal saline （NS）， and loxoprofen sodium according to the group to intervene， and sacrificed after 2-week administration. Synovium and cartilage histopathological changes were observed after hematoxylin-eosin （HE） staining. Flow cytometry （FCM） and immunofluorescence （IF） test were used to evaluate the polarization of M1/M2 macrophages. Immunohistochemistry （IMC） and enzyme-linked immunosorbent assay （ELISA） were used to detect the related protein expression levels of macrophage polarization， such as interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and matrix metalloproteinase-13 （MMP-13） in joint tissues and serum. ResultCompared with the sham operation group， Krenn and Mankin scores in the model group were significantly increased （P<0.01）. Compared with the model group， Krenn score was decreased in all administration groups （P<0.05， P<0.01）， but there was no significant difference in Mankin score in any administration groups. Compared with the sham operation group， M1/mø （CD38⁺） ratio in the model group was significantly increased （P<0.01）， and M2/mø （CD206⁺） ratio in the model group was decreased （P<0.05）. Compared with the model group， M1/mø ratio in the high， medium， and low-dose FHDP groups was decreased （P<0.05， P<0.01）， but M2/mø ratio was increased in all administration groups （the difference had no statistical significance）. Compared with the sham operation group， M1/M2 ratio in the model group was significantly increased （P<0.01）. Compared with the model group， M1/M2 ratio in all FHDP groups was significantly decreased （P<0.01）， and M1/M2 ratio in the high and medium-dose FHDP groups was lower than that in the loxoprofen sodium group （P<0.05）. Compared with the sham operation group， the levels of TNF-α， IL-1β， and MMP-13 in synovium and cartilage of the model group were significantly increased （P<0.01）， the level of IL-10 was significantly decreased （P<0.01）. Compared with the model group， the levels of TNF-α and IL-1β in synovium were decreased in all administration groups （P<0.05）， but the difference of the levels of MMP-13 and IL-10 in synovium had no statistical significance. The level of inflammatory mediators in cartilage was not affected in all administration groups. Compared with the sham operation group， the levels of TNF-α and IL-β in serum of the model group were significantly increased （P<0.01）， the level of IL-10 was decreased （P<0.05）. Compared with the model group， the level of TNF-α in the high-dose FHDP group was decreased （P<0.05）， and the level of IL-10 was increased in all administration groups （P<0.05， P<0.01）. The difference of the level of IL-β in all administration groups had no statistical significance. ConclusionFHDP attenuated the synovitis of KOA rats. FHDP exert the effect on the releasing of proinflammatory cytokines and MMP by inhibiting the polarization of M1 macrophages in synovium， and had no significant effect on the polarization of M2 macrophages. Modulating the imbalanced polarization of synovial macrophages was a possible mechanism of FHDP on attenuating synovitis and treating KOA.