ObjectiveTo investigate the effect and mechanism of Dendrobium mixture （DMix）-containing serum on high glucose-induced podocyte injury in mice. MethodThe MPC5 mouse glomerular podocytes were cultured in vitro， and the optimal glucose concentration for modeling， modeling time， and concentration of DMix-containing serum for administration were determined. The cells were classified into normal （5.5 mmol·L^-1 glucose+10% blank serum）， model （30 mmol·L^-1 glucose+10% blank serum）， DMix-containing serum （30 mmol·L^-1 glucose+10% DMix-containing serum）， ferroptosis inhibitor （Fer-1， 30 mmol·L^-1 glucose+10% blank serum+1 μmol·L^-1 Fer-1） groups. The corresponding kits were used to measure the levels of Fe²⁺ and lactate dehydrogenase （LDH） in cells. Enzyme-linked immunosorbent assay was employed to determine the content of glutathione （GSH） and lipid peroxide （LPO） in cells. Fluorescence probe was used to measure the reactive oxygen species （ROS） level. Real-time fluorescence quantitative polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels， respectively， of Wilms' tumor-1 （WT-1）， desmin， long chain acyl-CoA synthase 4 （ACSL4）， and glutathione peroxidase 4 （GPX4） in podocytes. ResultCompared with the blank group， the intervention with 30 mmol·L^-1 glucose for 48 h reduced podocyte viability （P<0.01）， and the 10% DMix-containing serum showed the most significant improvement in podocyte viability （P<0.01）. Compared with the normal group， the model group presented elevated levels of Fe²⁺， LDH， LPO， and ROS， lowered GSH level， up-regulated mRNA and protein levels of desmin and ACSL4， and down-regulated mRNA and protein levels of WT-1 and GPX4 （P<0.01）. Compared with the model group， the DMix-containing serum lowered the Fe²⁺， LDH， LPO， and ROS levels， elevated the GSH level， down-regulated the mRNA and protein levels of desmin and ACSL4， and up-regulated the mRNA and protein levels of WT-1 and GPX4 in podocytes （P<0.05， P<0.01）. ConclusionDMix-containing serum exerts a protective effect on high glucose-induced podocyte injury by inhibiting ferroptosis.

Objective To analyze the effect of night-shift work, anxiety and their interaction on work-related musculoskeletal disorders (WMSDs) among electronics manufacturing employees. Methods A total of 2 676 employees from 58 electronic manufacturing enterprises in the Pearl River Delta region of Guangdong Province were selected as the research subjects using the judgment sampling method. The Basic Situation Survey Scale, Generalized Anxiety Disorder 7-item Scale and Questionnaire of Musculoskeletal Disorders were used to assess night-shift work, anxiety and the prevalence of WMSDs in employees. The multivariate logistic regression model was used to analyze the effects of night-shift work, anxiety and their combined effects on the risk of WMSDs. Results The proportion of night-shift work was 30.3%, and the detection rates of anxiety and WMSDs were 26.8% and 41.3%, respectively. The results of multivariate logistic regression analysis showed that night-shift work and anxiety were independent risk factors of WMSDs in the research subjects, after excluding the influence of confounding factors such as age, marital status, enterprise size and length of service [odds ratio (OR) and 95% confidence interval (CI) were 1.307 (1.092-1.564) and 3.282 (2.739-3.934), respectively, both P<0.01]. Compared with those without night-shift work or anxiety, the risk of WMSDs was higher in individuals with only night-shift work, only anxiety, or both night-shift work and anxiety [OR and 95%CI were 1.347 (1.091-1.663), 3.395 (2.727-4.227) and 4.117 (3.072-5.519), respectively, all P<0.01]. Conclusion Both night-shift work and anxiety can increase the risk of WMSDs among electronic manufacturing employees, and these two factors exhibit a synergistic effect in increasing the risk of WMSDs.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Abstract: Objectives　To sequence the whole genome of Vibrio cholerae strains isolated from Fuzhou between 2018 and 2023, predict virulence genes, antimicrobial resistance genes, and sequence loci information, analyze the genetic relationships among different strains, and provide evidence for cholera prevention and control. Methods　Whole genome sequencing was performed on 60 strains of Vibrio cholerae, and bioinformatics software was used for quality control, gene assembly, and prediction of the sequencing data. PubMLST, ResFinder, and VFDB databases were used to predict the multilocus sequence typing, antimicrobial resistance genes, and virulence genes of different strains. Combined with the NCBI database, the phylogenetic tree was constructed by the maximum likelihood method through the core cgSNP phylogenetic analysis and de-recombination analysis. Results Based on the typing of 7 housekeeping genes, 60 Vibrio cholerae strains can be categorized into 16 known STs and 38 newly assigned STs. The clinical isolate H339 of serogroup O1 was identified as ST75. Serogroup O1 food isolates H13, H363, and H381 were all ST175. H263 and H357, the NOVC isolates, were both ST1218. H293 and H306 were ST1700. H311, H314, and H316 were all ST1699, with the remaining isolates displaying diversity. A total of 29 antimicrobial resistance genes were predicted, including aminoglycosides, β-lactams, quinolones, and folate pathway antagonists, with the majority of the strains carrying quinolones antimicrobial resistance genes. According to the VFDB prediction, all isolates had the virulence factors rtx and hlyA, 96.7% (58/60) of the strains carried the tlh genes, all serogroup O1 isolates carried tcp, zot, and ace genes, and all serogroup O1 clinical isolates carried ctxA genes. Phylogenetic tree analysis of the whole genome divided all strains into 20 branches, indicating high genomic divergence. Conclusions　Thirty-eight new STs were identified. Genetic correlations were found among serogroup O1 food isolates, whereas serogroup O1 clinical isolates and serogroup O1 food isolates, as well as between serogroup O1 and NOVC strains, show distant phylogenetic relationships. There was diversity among the isolates. This study provides data support for the traceability of foodborne diseases.

Humans ; East Asian People ; Genetic Profile ; Mutation ; Osteochondrodysplasias/genetics*

Objective:To introduce a surgical method and clinical effect of using Masquelet technique combined with skin graft to cover chronic refractory wounds in elderly patients.Methods:From September 2020 to September 2022, 20 elderly patients with wounds of bone or tendon exposure in lower limbs were treated in the Department of Wound Repair, the Second Affiliated Hospital of Wenzhou Medical University. Due to the age and poor general condition of the patients, flap transfer for wound coverage were not allowed. Masquelet technique was therefore applied in the treatment of chronic wounds of such patients. Sizes of wounds were found at 4.5 cm×3.0 cm to 15.0 cm×6.0 cm and all accompanied with tendon and bone exposure, after thorough debridement. Wounds were then sealed with antibiotic bone cement several times. After having induced formation of membrane in wounds, free mesh skin graft was used to cover the refractory wounds. The patients were entered in follow up regularly after surgery at outpatient service, and telephone or video reviews. The wound healing of patients and whether there were related complications in the skin donor area were observed. The number of operation times in the first stage was 1-4 with an average of 1.3 times ± 0.7 times. Lower Extremity Function Scale (LEFS) was used to evaluate the recovery of lower limb function.Results:All 20 wounds healed well. The follow-up time was 3-12 months, with an average of 7.6 months. The appearance and texture of the skin in the wounds area were satisfactory. The mean LEFS was 69.83 point ± 10.82 point.Conclusion:Using Masquelet technique combined with free skin grafting to treat refractory wounds in the elderly patients can achieve satisfactory clinical outcomes. It is a simple and reliable supplement to the wound repair, and can reduce the surgical risk.

Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of K _d = 99.08 nmol/L. DC-PGKI stabilizes PGK1 in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. In addition, DC-PGKI unveils that PGK1 regulates production of IL-1β and IL-6 in LPS-stimulated macrophages. Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2 (nuclear factor-erythroid factor 2-related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1β and Il-6 genes, and inhibits LPS-induced expression of these genes. DC-PGKI ameliorates colitis in the dextran sulfate sodium (DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease.

Objective:To investigate the clinical effect of local and systemic zoledronic acid in the treatment of giant cell tumor of bone.Methods:The clinical data of 42 patients with giant cell tumor of bone who were treated in the Department of Joint and Sports Medicine Surgery of Shandong Provincial Third Hospital from January 2000 to January 2017 were retrospectively analyzed. According to whether zoledronic acid was used during and after operation, the patients were divided into zoledronic acid group ( n=21) and non zoledronic acid group ( n=21). The perioperative indexes, pain visual analogue scale (VAS), international Musculoskeletal Tumor Society (MSTS) score of lower extremity function, adverse reactions and the postoperative recurrence were compared between the two groups. Results:The operative time of zoledronic acid group and non zoledronic acid group were (158.4±20.5) min and (169.5±19.5) min, the intraoperative bleeding volume were (236.3±9.7) ml and (228.2±16.5) ml, the postoperative drainage volume were (163.3±7.4) ml and (161.4±9.3) ml, and the healing time of incision were (13.8±2.1) d and (14.0±2.0) d, respectively, with no significant difference ( t=-1.798, P=0.080; t=1.936, P=0.062; t=0.733, P=0.468; t=-0.290, P=0.774). The preoperative VAS scores of zoledronic acid group and non zoledronic acid group were 6.54±1.76 and 6.72±1.51 respectively, the MSTS scores were 13.56±2.35 and 12.79±1.98 respectively, and the differences were not statistically significant ( t=-0.356, P=0.724; t=1.148, P=0.258). The VAS scores of the two groups were 1.32±0.31 and 1.92±0.19 at 4 weeks after operation, 0.93±0.29 and 1.47±0.38 at 3 months after operation respectively, and the differences were statistically significant ( t=-7.562, P<0.001; t=-5.177, P<0.001). The VAS scores of the two groups were 0.31±0.12 and 0.35±0.23 at the last follow-up, with no significant difference ( t=0.707, P=0.485). The MSTS scores of zoledronic acid group and non zoledronic acid group were 24.89±3.86 and 21.82±2.95 at 4 weeks after operation, 26.78±2.57 and 24.62±2.62 at 3 months after operation respectively, and the differences were statistically significant ( t=2.896, P=0.006; t=2.697, P=0.010). The MSTS scores of the two groups were 27.31±2.21 and 26.69±2.93 at the last follow-up, with no significant difference ( t=0.774, P=0.443). The postoperative recurrence time of the two groups was (9.79±2.58) months and (7.31±1.73) months respectively, and the difference was statistically significant ( t=3.659, P=0.001). There was no significant difference in recurrence Campanacci grade and recurrence tumor location between the two groups ( U=7.000, P=0.860; χ2=1.062, P>0.999). The occurrence rates of fever in zoledronic acid group and non zoledronic acid group were 23.81% (5/21) and 4.76% (1/21), the occurrence rates of myalgia were 19.05% (4/21) and 4.76% (1/21), the incidences of influenza like symptoms were 14.29% (3/21) and 0 (0/21), the occurrence rates of gastrointestinal reaction were 9.52% (2/21) and 4.76 (1/21), and the differences were not statistically significant ( χ2=1.750, P=0.186; χ2=0.980, P=0.341; χ2=1.436, P=0.231; χ2<0.001, P>0.999). All the patients had no serious adverse reactions such as liver and kidney function damage and mandible necrosis. Conclusion:Local and systemic application of zoledronic acid in the treatment of giant cell tumor of bone can improve the early postoperative pain and limb function, delay the recurrence time, and can be used as an auxiliary treatment of giant cell tumor of bone.

Objective To evaluate the role of hippocampal CD200 receptor 1(CD200R1)in peri-operative neurocognitive disorders(PND)in mice.Methods Sixty clean-grade male C57BL/6 mice,aged 9-10 months,weighing 32-38 g,were used in the study.The experiment was performed in two parts.Ex-periment Ⅰ Thirty-six mice were divided into 2 groups(n＝18 each)using a random number table meth-od: control group(group C)and PND group.Group C only received isoflurane anesthesia.Partial left lo-bectomy of the liver was performed under isoflurane anesthesia in group PND.Contextual fear conditioning test was performed at 1,3 and 7 days after surgery,and the freezing time was recorded.The mice were then sacrificed,and the hippocampus was isolated for determination of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)contents(by enzyme-linked immunosorbent assay)and CD200 and CD200R1 expression(by Western blot).ExperimentⅡ Twenty-four mice were divided into 2 groups(n＝12 each)using a random number table method: CD200-Fc group and IgG1-Fc group.Recombinant proteins CD200-Fc and human IgG1-Fc were injected into the lateral cerebral ventricle in CD200-Fc group and IgG1-Fc group,respectively.Partial left lobectomy of the liver was performed after the end of injection.Contextual fear conditioning test was performed at 1 and 3 days after surgery,and the freezing time was recorded.Re-sults Experiment Ⅰ Compared with group C,the freezing time in the contextual fear conditioning test was significantly shortened,and the contents of IL-1β were increased at 1 and 3 days after surgery,the contents of TNF-α were increased at 3 and 7 days after surgery,and the expression of CD200 and CD200R1 was up-regulated at 1 day after surgery in group PND(P＜0.05).ExperimentⅡ Compared with IgG1-Fc group,the freezing time in the contextual fear conditioning test was significantly prolonged at 1 day after surgery in CD200-Fc group(P＜0.05).Conclusion Up-regulated expression of hippocampal CD200R1 is the endogenous protective mechanism of PND in mice.

Objective: To evaluate the role of hippocampal CD200 receptor 1 (CD200R1) in perioperative neurocognitive disorders (PND) in mice. Methods: Sixty clean-grade male C57BL/6 mice, aged 9-10 months, weighing 32-38 g, were used in the study.The experiment was performed in two parts.Experiment Ⅰ Thirty-six mice were divided into 2 groups (n=18 each) using a random number table method: control group (group C) and PND group.Group C only received isoflurane anesthesia.Partial left lobectomy of the liver was performed under isoflurane anesthesia in group PND.Contextual fear conditioning test was performed at 1, 3 and 7 days after surgery, and the freezing time was recorded.The mice were then sacrificed, and the hippocampus was isolated for determination of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) contents (by enzyme-linked immunosorbent assay) and CD200 and CD200R1 expression (by Western blot). Experiment Ⅱ Twenty-four mice were divided into 2 groups (n=12 each) using a random number table method: CD200-Fc group and IgG1-Fc group.Recombinant proteins CD200-Fc and human IgG1-Fc were injected into the lateral cerebral ventricle in CD200-Fc group and IgG1-Fc group, respectively.Partial left lobectomy of the liver was performed after the end of injection.Contextual fear conditioning test was performed at 1 and 3 days after surgery, and the freezing time was recorded. Results: Experiment Ⅰ Compared with group C, the freezing time in the contextual fear conditioning test was significantly shortened, and the contents of IL-1β were increased at 1 and 3 days after surgery, the contents of TNF-α were increased at 3 and 7 days after surgery, and the expression of CD200 and CD200R1 was up-regulated at 1 day after surgery in group PND (P<0.05). Experiment Ⅱ Compared with IgG1-Fc group, the freezing time in the contextual fear conditioning test was significantly prolonged at 1 day after surgery in CD200-Fc group (P<0.05). Conclusion Up-regulated expression of hippocampal CD200R1 is the endogenous protective mechanism of PND in mice.