Objective:To investigate the effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats.Methods:This study was an experimental study. Eighteen 8-week-old male Sprague Dawley rats were divided into control group, diabetes group, and diabetes+metformin group according to complete random grouping method, with 6 rats in each group. The latter two groups of rats were used to create diabetic models, and then four circular full-thickness skin defect wounds with a diameter of 5 mm were made on the back of 18 rats. Metformin F-127 hydrogel was applied only to the wounds of rats in diabetes+metformin group. The wound healing status on post injury day (POD) 7 and 13 was observed and the wound healing rate was calculated. The wound tissue on POD 7 and 13 was collected for hematoxylin-eosin staining to measure the length of re-epithelialized epidermis and calculate the change rates in diameters of epidermal and dermal wounds, for immunohistochemical staining to detect the relative expressions of keratin 10 and proliferating cell nuclear antigen (PCNA), and for Western blotting to detect the protein expressions of keratin 10 and PCNA. The sample size in all the above experiments was 8 except that in the last experiment was 3. The correlations between the relative expressions of keratin 10 and PCNA in wound tissue in three groups of rats and their wound healing rates, and the correlation between the relative expressions of keratin 10 and PCNA in wound tissue were analyzed.Results:On POD 7, the wound healing rates of rats in diabetes group and diabetes+metformin group were 81.48% (77.89%, 85.53%) and 93.04% (92.51%, 94.24%), which were significantly lower than 100% (97.17%, 100%) in control group (with Z values of 2.37 and -3.36, respectively, P<0.05); the wound healing rate of rats in diabetes+metformin group was significantly higher than that in diabetes group ( Z=3.45, P<0.05). On POD 13, the wound healing rates of rats in control group and diabetes+metformin group were both 100% (100%, 100%), which were significantly higher than 94.47% (90.68%, 99.82%) in diabetes group (with Z values of 2.90 and -2.90, respectively, P<0.05). On POD 7, the change rates in epidermal wound diameter of rats in control group and diabetes+metformin group were significantly higher than that in diabetes group (with Z values of 3.36 and -2.74, respectively, P<0.05). The change rates in dermal wound diameter of rats in the three groups were similar on POD 7 and 13 ( P>0.05). The lengths of re-epithelialized epidermis of rats in control group and diabetes+metformin group on POD 13 were significantly longer than that in diabetes group (with Z values of 3.34 and -2.64, respectively, P<0.05). The relative expressions of keratin 10 in wound tissue of rats in diabetes group on POD 7 and 13 were significantly higher than those in control group (with Z values of -3.36 and -3.26, respectively, P<0.05) and diabetes+metformin group (with Z values of 3.36 and 3.15, respectively, P<0.05), and the relative expression of keratin 10 in wound tissue of rats in diabetes+metformin group on POD 7 was significantly lower than that in control group ( Z=3.05, P<0.05); the relative expressions of PCNA in wound tissue of rats in diabetes group on POD 7 and 13 were significantly lower than those in control group (with both Z values of 3.36, P<0.05) and diabetes+metformin group (with both Z values of -3.36, P<0.05). The protein expressions of keratin 10 in wound tissue of rats in control group and diabetes+metformin group on POD 7 as well as that in diabetes+metformin group on POD 13 were significantly lower than those in diabetes group ( P<0.05), and the protein expressions of PCNA in wound tissue of rats in control group and diabetes+metformin group on POD 7 were significantly higher than that in diabetes group ( P<0.05). There was a significant positive correlation between the relative expression of keratin 10 in wound tissue and the wound healing rate in control group and diabetes+metformin group of rats (with r values of 0.78 and 0.71, respectively, P<0.05), there was a significant negative correlation between the relative expression of PCNA in wound tissue and the wound healing rate in diabetes+metformin group of rats ( r=-0.60, P<0.05), and there was a significant negative correlation between the relative expressions of PCNA and keratin 10 in wound tissue of rats in diabetes group and diabetes+metformin group (with r values of -0.41 and -0.49, respectively, P<0.05). Conclusions:The diabetic rats with full-thickness skin defect wound exhibit delayed healing, accompanied by up-regulation of keratin 10 and down-regulation of PCNA in keratinocytes in the wound tissue. Metformin can promote wound healing in diabetic rats with full-thickness skin defects by down-regulating keratin 10 expression and up-regulating PCNA expression in keratinocytes in the wound tissue, and the wound healing rate was positively correlated with the expression of keratin 10 and negatively correlated with the expression of PCNA.

Objective:To investigate the correlation between cardiac polyps and gastroesophageal flap valve (GEFV).Methods:The clinical, endoscopic and pathological data of 349 patients with cardiac polyps (the cardiac polyp group) visiting Affiliated Hospital of Yangzhou University from January 1, 2016 to December 31, 2021 were retrospectively collected, and the same number of non-cardiac polyp patients (the non-cardiac polyp group) were matched in the same period as control according to the propensity score. The clinical, endoscopic and pathological data of the two groups were compared.Results:After matching with propensity score, there were 296 patients in each group, with no significant differences in smoking, acid reflux, heartburn, Helicobacter pylori infection, bile reflux, reflux esophagitis or pancreatitis between the two groups ( P>0.05). Compared with the non-cardiac polyp group, the risk of cardiac polyps increased in GEFV Ⅱ patients ( OR=3.046, 95%CI: 2.100-4.419, P<0.001) and GEFV Ⅲ patients ( OR=4.202, 95%CI: 2.299-7.681, P<0.001). Compared with the non-cardiac polyp group, the risk of cardiac polyps increased in patients with GEFV abnormalities ( OR=2.822, 95%CI: 1.615-4.931, P<0.001). GEFV abnormalities was associated with the cardiac polyp site ( χ2=22.169, P=0.003) and was not significantly associated with cardiac polyp size, number, morphology, intestinal metaplasia of the surrounding mucosa or intraepithelial neoplasia ( P>0.05). Conclusion:The occurrence of cardiac polyps is related to GEFV, and the patients with GEFV abnormalities are more likely to develop cardiac polyps.

Objective: To evaluate the efficacy and safety of Jiawei Simiao powder (JWSMP) combined with celecoxib for the treatment of acute gouty arthritis by conducting a meta-analysis of randomized controlled trials (RCTs). Methods: The Chinese National Knowledge Infrastructure Databases, Chinese Scientific Journal Database, Wanfang, Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched from inception until December 2023. Continuous variables were analyzed using the mean difference (MD) for analysis, and dichotomous variables were used as risk ratios. Data with similar characteristics were pooled for meta-analysis, and heterogeneity was assessed using I2. The Cochrane Handbook was used to assess the risk of bias and quality. RevMan 5.3 software was used to perform the meta-analysis. Results: Thirteen RCTs involving 1007 patients were included in the study. The quality of the included studies was low (unclear randomization processes and insufficient blinding reporting). The group receiving JWSMP combined with celecoxib showed significantly lower levels of serum uric acid (SUA, MD = −66.32, 95% confidence interval (CI): −80.97 to −51.67, P < .001), erythrocyte sedimentation rate (ESR, MD = −6.05, 95% CI: −8.29 to −3.82, P < .001), C-reactive protein (CRP, MD = −7.39, 95% CI: −11.15, −3.63, P < .001), and joint pain score (VAS score, MD = −2.14, 95% CI: −2.4 to −1.88, P < .001) compared to celecoxib alone. Additionally, the JWSMP combined group had a higher total effective rate (risk ratio = 1.22, 95% CI: 1.14 to 1.29, P < .001) and fewer adverse compared to celecoxib alone. Conclusions JWSMP combined with celecoxib is more effective than celecoxib alone in improving the total efficacy rate, alleviating joint pain, and improving SUA, ESR, and CRP levels. JWSMP also reduced the occurrence of adverse events caused by celecoxib. However, the quality of the included studies was low, highlighting the need for further high-quality research with larger sample sizes and robust methodologies, such as double-blind randomization, to confirm these findings.

Objective:To predict the possible targets and signaling pathways of Jiangtang Xiaoke Granules in the treatment of diabetes mellitus (DM) using computer network pharmacology and molecular docking technology.Methods:The active components and targets of Jiangtang Xiaoke Granules were collected by ETCM; the targets of DM were searched from the databases of DisGeNET and GeneCards, and the intersections of the two were taken to draw a Venny diagram; String database was used for gene transformation and network interaction analysis; the network diagram was constructed with Cytoscape3.6.0; the predicted results were supported by molecular docking technology; GO and KEGG analysis was performed through Metascape database.Results:A total of 128 active components of Jiangtang Xiaoke Granules were screened, with 607 corresponding targets, 1 240 DM related targets, and 53 core targets. Molecular docking showed that the active components had good binding energy with the core targets. GO analysis yielded 46 functional items and KEGG analysis yielded 15 pathways.Conclusion:Jiangtang Xiaoke Granules regulate glucose homeostasis by participating in a variety of biological processes through multiple components, and multiple targets, including affecting lipids and atherosclerosis, Alzheimer disease, AMPK signaling pathway, Apelin signaling pathway, and glucagon signaling pathway.

Objective:To investigate the preventive effect of postoperative pancreatic fistula by pedicled omentum wrapping pancreaticojejunostomy in pancreaticoduodenectomy.Methods:The clinical data of 78 patients who underwent pancreaticoduodenectomy in Songjiang Hospital Affiliated to Shanghai Jiao Tong University from September 2017 to August 2020 were retrospectively analyzed. Patients were divided into the modified pancreaticojejunostomy group (conventional approach group, n=43) and the pedicled omentum wrapping pancreaticojejunostomy group (omentum wrapping group, n=35) according to the surgical mode. Postoperative pancreatic fistula, postoperative abdominal bleeding, delayed gastric emptying and postoperative hospital stay were compared between the two groups. Results:Compared with the conventional approach group, the postoperative pancreatic fistula rate in omentum wrapping group was significantly reduced (2.9% vs 18.6%), and the difference was statistically different ( P=0.030); postoperative abdominal bleeding rate(0 vs 4.7%)and the delayed gastric emptying rate were significantly reduced (8.6% vs 25.6%), but both of them were not statistically different ( all P value>0.05); the length of postoperative hospital stay was significantly reduced [(11.3±2.9) days vs (12.8±3.5)days], and the difference was statistically different ( P=0.045). Conclusions:The pedicled omentum wrapping pancreaticojejunostomy was simple and convenient, which can significantly reduce the rate of postoperative pancreatic fistula. It can shorten the time of the length of hospital stay after surgery.

Objective:To investigate the value of brainstem auditory evoked potential (BAEPs) combined with cochlear electrogram (ECochG) monitoring in the protection of auditory function during microvascular decompression (MVD) for patients with facial spasm (HFS).Methods:Clinical data of 908 patients with HFS who received MVD treatment in our hospital from January 2018 to December 2020 were retrospectively analyzed. The patients were divided into BAEPs group ( n=309), ECochG group ( n=301) and BAEPs+ECochG group ( n=298) according to the different methods of auditory nerve function monitoring. Waveform extraction rate, mean extraction time, amplitude, latency, intraoperative warning effect of 3 monitoring methods, as well as hearing status immediately after surgery and during follow-up were compared in patents from the 3 groups. Results:(1) The overall waveform extraction rate in ECochG group and BAEPs+ECochG group was significantly higher than that in BAEPs group, and the average waveform extraction time in ECochG group and BAEPs+ECochG group was significantly shorter than that in BAEPs group ( P<0.05). The amplitude of compound action potential (CAP) wave in ECochG group was significantly higher than that of V wave in BAEPs group, and the latency of CAP wave was also significantly earlier than that of V wave ( P< 0.05). (2) A total of 48 patients of the 288 patients in the BAEPs group showed warning signs; a total of 73 of the 292 patients in the ECochG group showed warning signs; and a total of 65 of the 292 patients in the BAEPs+ECochG group showed warning signs. (3) There was significant difference in hearing grading (American Association of Otolaryngology Head and Neck Surgery [AAO-HNS] grading) among the 3 groups immediately after surgery ( H=18.041, P=0.000), and the average rank suggested that the hearing of patients in the BAEPs+ECochG group was superior to the other two groups. All patients were followed up for an average of 15 months (ranged 3-24 months); there was still a significant difference in AAO-HNS grading among the 3 groups ( H=29.625, P=0.000), and the hearing of patients in the BAEPs+ECochG group was still superior to the other two groups. Conclusion:The combined application of ECochG and BAEPs monitoring can reflect the changes of intraoperative hearing impairment comprehensively, accurately and timely, which is of great significance for the protection of auditory function in HFS patients during MVD.

Isatis indigotica Fort. (Ban-Lan-Gen) is an herbal medicine prescribed for influenza treatment. However, its active components and mode of action remain mostly unknown. In the present study, erucic acid was isolated from Isatis indigotica Fort., and subsequently its underlying mechanism against influenza A virus (IAV) infection was investigated in vitro and in vivo. Our results demonstrated that erucic acid exhibited broad-spectrum antiviral activity against IAV resulting from reduction of viral polymerase transcription activity. Erucic acid was found to exert inhibitory effects on IAV or viral (v) RNA-induced pro-inflam-matory mediators as well as interferons (IFNs). The molecular mechanism by which erucic acid with antiviral and anti-inflammatory properties was attributed to inactivation of NF-kB and p38 MAPK signaling. Furthermore, the NF-kB and p38 MAPK inhibitory effect of erucic acid led to diminishing the transcriptional activity of interferon-stimulated gene factor 3 (ISGF-3), and thereby reducing IAV-triggered pro-inflammatory response amplification in IFN-β-sensitized cells. Additionally, IAV- or vRNA-triggered apoptosis of alveolar epithelial A549 cells was prevented by erucic acid. In vivo, erucic acid administration consistently displayed decreased lung viral load and viral antigens expression. Meanwhile, erucic acid markedly reduced CD8+cytotoxic T lymphocyte (CTL) recruitment, pro-apoptotic signaling, hyperactivity of multiple signaling pathways, and exacerbated immune inflammation in the lung, which resulted in decreased lung injury and mortality in mice with a mouse-adapted A/FM/1/47-MA(H1N1) strain infection. Our findings provided a mechanistic basis for the action of erucic acid against IAV-mediated inflammation and injury, suggesting that erucic acid may have a therapeutic potential in the treatment of influenza.

OBJECTIVE: To develop a radioactive sewage purification device that can effectively filter the nuclides in low-level nuclide-contaminated wastewater. METHODS: The radioactive sewage purification device was composed of lifting pump, stack filter, multi-medium filter, security filter, tubular ultrafiltration membrane, high-pressure pump and reverse osmotic membrane. The combined process of adsorption-ultrafiltration-reverse osmosis was used to separate radioactive elements from wastewater by reverse osmosis membrane separation system. Through two-stage multi-medium filter circulation system circulation treatment, radioactive sewage was purified. The flow rate of water treatment is 20 L/min. The filtration efficiency and purification efficiency of the device were tested by filtration experiments on elements containing radionuclide and purification experiments on radionuclide.RESULTS: The filtration efficiency on iodine, potassium, strontium and cesium, that are the common elements in radioactive sewage samples were 97.88%, 98.38%, 99.99% and 99.80%, respectively. The single purification efficiency of radionuclide ~(40)K in low-level radioactive sewage was over 90.00%. CONCLUSION: The device has high filtering efficiency for common elements such as iodine, potassium, strontium and cesium in sewage and high removal rate of radioactive activity for sewage containing ~(40)K. It can be further optimized and transformed into a suitable radioactive sewage water purifier.

Objective:To observe and analyze the risk factors related to vitreous re-hemorrhage (PVH) after anti-VEGF drugs combined with vitrectomy (PPV) in patients with proliferative diabetic retinopathy (PDR).Methods:Retrospective analysis study. From April 2017 to July 2018, 100 eyes of 87 PDR patients who were diagnosed in Jiaxing Eye Hospital and received anti-VEGF drugs combined with 25G PPV were included in the study. Among them, there were 44 eyes in 38 males and 56 eyes in 49 females. The age ranged from 26 to 83 years, with an average age of 57.72±8.82 years. All patients were type 2 diabetes, with an average duration of diabetes 10.84±6.03 years. All affected eyes were assisted by the same doctor with a non-contact wide-angle lens under the standard three-channel 25G PPV of the flat part of the ciliary body. Five to 7 days before the operation, intravitreal injection of ranibizumab or conbercept 0.05 ml (10 mg/ml) was performed. The incidence of PVH was observed. The age of PVH patients, duration of diabetes, vision before operation, average fasting blood glucose and average postprandial blood glucose before operation, systolic blood pressure and diastolic blood pressure before surgery, laser treatment before surgery, lens removal during operation, intraocular filling during operation, retinal laser points during operation, and fundus lesions during operation (hyperplasia film, Retinal hemorrhage, vascular occlusion, proliferative retinal traction, retinal hiatus, retinal detachment, exudation, neovascularization) were analyzed to find out the cause of PVH. Spearman bivariate correlation analysis and binary logistic regression analysis were performed on the data.Results:Of the 100 eyes of 87 patients, PVH occurred in 17 eyes (17%). There were statistically significant differences in the number of eyes with vascular occlusion and proliferative traction during surgery in patients with and without PVH ( χ2=5.741, 8.103; P<0.05). There was no significant difference in age ( t=-1.364), duration of diabetes ( t=0.538), preoperative vision ( t=1.897), preoperative fasting blood glucose level ( t=1.938), preoperative postprandial blood glucose level ( t=1.508), preoperative systolic blood pressure ( t=-0.571), preoperative diastolic blood pressure ( t=0.275), whether received laser treatment ( χ2=2.678), the number of laser points during operation ( t=0.565), whether received lens removal during operation ( χ2=0.331), whether found new blood vessels during operation ( χ2=2.741) and whether received intraocular filling during operation ( χ2=0.060) between the patients with and without PVH ( P>0.05). Spearman's bivariate correlation analysis showed that patients with low vision, poor control of fasting blood glucose levels, vascular occlusion and proliferative retinal traction during the operation were related risk factors for PVH ( rs=0.208, 0.229, 0.240, 0.285; P<0.05). Binary logistic regression analysis showed that fundus vascular occlusion and hyperplastic retinal traction may be independent risk factors for PVH during surgery ( OR=5.175, 13.915; P<0.05). Conclusion:Fundus vascular occlusion and retinal traction caused by fibrovascular membrane hyperplasia in PPV may be independent risk factors for PVH in patients with PDR after anti-VEGF drugs combined with PPV.

Leishmaniasis is a prevalent cause of death and animal morbidity in underdeveloped countries of endemic area. However, there is few vaccine and effective drugs. Antimicrobial peptides are involved in the innate immune response in many organisms and are being developed as novel drugs against parasitic infections. In the present study, we synthesized a 5-amino acid peptide REDLK, which mutated the C-terminus of Pseudomonas exotoxin, to identify its effect on the Leishmania tarentolae. Promastigotes were incubated with different concentration of REDLK peptide, and the viability of parasite was assessed using MTT and Trypan blue dye. Morphologic damage of Leishmania was analyzed by light and electron microscopy. Cellular apoptosis was observed using the annexin V-FITC/PI apoptosis detection kit, mitochondrial membrane potential assay kit and flow cytometry. Our results showed that Leishmania tarentolae was susceptible to REDLK in a dose-dependent manner, disrupt the surface membrane integrity and caused parasite apoptosis. In our study, we demonstrated the leishmanicidal activity of an antimicrobial peptide REDLK from Pseudomonas aeruginosa against Leishmania tarentolae in vitro and present a foundation for further research of anti-leishmanial drugs.