Objective To investigate the association between the Chinese visceral adiposity index (CVAI) and diabetes mellitus, hypertension, diabetes mellitus or hypertension, and diabetes with hypertension among elderly people in Hebei Province. Methods In 2020, a stratified multi-stage random sampling was used to conduct questionnaire survey, physical examination and laboratory detection among permanent residents of 10 monitoring sites in Hebei Province. Logistic regression was used to analyze the association between CVAI and diabetes mellitus, hypertension, diabetes mellitus or hypertension, and diabetes with hypertension. The area under the ROC curve (AUC) was used to evaluate the predictive value of CVAI for diabetes mellitus, hypertension, diabetes mellitus or hypertension, and diabetes with hypertension. Results The detection rates of diabetes mellitus, hypertension, diabetes mellitus or hypertension, and diabetes with hypertension were 19.8%, 74.6%, 78.2%, and 16.2%, respectively. Multivariate logistic regression analysis showed that compared with the lowest quartile of CVAI group Q1, the OR (95% CI) of diabetes mellitus, hypertension, diabetes mellitus or hypertension, and diabetes with hypertension in the highest quartile Q4 group were 3.55 (2.58~4.89), 2.52 (1.92~3.31), 3.09 (2.31~4.12), and 4.92 (3.40~7.12), respectively. The ROC curve results showed that CVAI had the best predictive value in the diagnosis of diabetes with hypertension, and the optimized critical values in males and females were 128.54 and 141.88, respectively. Conclusion The detection rates of diabetes mellitus and hypertension are high in the elderly population in Hebei Province. CVAI is positively associated with the risk of diabetes mellitus, hypertension, diabetes mellitus or hypertension, and diabetes with hypertension among the elderly in Hebei. CVAI has the strongest prediction ability for diabetes with hypertension.

Objectives:To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)—NP@Pt(Ⅳ) in ovarian cancer.Methods:Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)—Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured.Results:The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment ( P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 μmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 μmol/L) and cisplatin (5.21, 11.85, and 71.98 μmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm 3, which was significantly lower than those in control group [(1 349±161) mm 3, P<0.001] and cisplatin group [(715±293) mm 3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion:Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

Objective Under the background of"breaking the Five-Only"and the evaluation reform of healthcare professionals'titles,it analyzed the willingness of healthcare professionals in public hospitals to disseminate health knowledge and its incentives and constraints.Furthermore,it explored potential pathways to improve the willingness of healthcare professionals to popular science and disseminate health knowledge.Methods From November to Decem-ber 2022,a self-designed online questionnaire was used to survey healthcare professionals in four tertiary hospitals in Shanghai.The questionnaire included basic information of healthcare professionals,analysis of the current situa-tion and demands of healthcare professionals in health knowledge dissemination,willingness of healthcare profes-sionals to disseminate health knowledge and influencing factors.Results A total of 762 healthcare professionals partici-pated in this survey,79.9%(608/762)expressed willingness to promote the dissemination of health knowledge.A multiple-factor logistic regression analysis revealed that intermediate professional title,achieving personal value and so-cial responsibility,increasing patient resources,professional title promotion,science promotion-related awards,being included in performance appraisals,and difficulty in capturing science promotion skills were the influential factors affecting the dissemination of health knowledge among healthcare professionals(P＜0.05).Conclusion The willing-ness of healthcare professionals to disseminate health knowledge was strong,and hospitals should motivate health-care professionals to disseminate health knowledge through building a long-term incentive mechanism,strengthening training in science popularization ability,and improving humanistic qualities.

Objective:Methamphetamine(METH)is an illicit psychoactive substance that can damage various organs,with the urinary system being one of its significant targets.This study aims to explore the role of microtubule affinity-regulating kinase 4(MARK4)in METH-induced acute kidney injury(AKI). Methods:A total of 10 healthy adult male C57BL/6 mice were randomly divided into a control group and a METH group,5 mice in each group.The METH group was administered METH(20 mg/kg,intraperitoneally,once daily for 3 consecutive days),while the control group received an equal volume of physiological saline.The mice were executed 24 hours after the final injection,and the success of the AKI model was detected by blood serum creatinine,blood urea nitrogen,and renal HE staining.Proteins differentially expressed between kidney tissues with METH-induced AKI and normal kidney tissues were screened by proteomics techniques and subjected to gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)and bioinformatics analysis.The accuracy of proteomic data was validated using Western blotting,and the expression levels of MARK4 and cleaved caspase-3 in mouse kidneys were measured.We further explored the role of MARK4 in METH-induced AKI.Firstly,a METH toxicity model was established in BUMPT cells to screen the appropriate concentration and time of METH treatment;the viability of BUMPT cells after METH treatment and the expression of cleaved caspase-3 were detected by interfering with MARK4 expression through inhibitors. Results:The proteomic analysis of kidney tissues from METH and control groups screened for a total of 17 differentially expressed proteins,of which 11 were up-regulated and 6 were down-regulated(all P＜0.05).The expression levels of MARK4 and cleaved caspase-3 were elevated in the kidneys of METH-treated mice(both P＜0.05).The activity of BUMPT cells gradually decreased with increasing METH treatment concentration(all P＜0.05),where the viability of BUMPT cells decreased to about 60％after METH treatment at 4 mmol/L.Compared with the control group,expression levels of MARK4 and cleaved caspase-3 were increased with higher METH concentrations and longer exposure times in a concentration-and time-dependent manner(all P＜0.05).Inhibition of MARK4 expression improved METH-induced decrease in BUMPT cell activity,down-regulated the expression of cleaved caspase-3,and decreased the apoptosis of BUMPT cells induced by METH. Conclusion:MARK4 is highly expressed in a mouse model of METH-induced AKI,and MARK4 mediates METH-induced AKI by regulating cell apoptosis.

Objective To investigate the relationship between enlarged perivascular spaces in the hippocampus(H-EPVS)and cognitive function in patients with type 2 diabetes mellitus(T2DM),and to explore whether the H-EPVS can be used as an imaging marker of cognitive impairment in T2DM.Methods A total of 93 T2DM patients were selected(including 56 patients with cognitive impair-ment and 37 patients with normal cognition).All patients received head MRI scanning and neuropsychological tests.The differences of the H-EPVS counts and various parameters between the two groups were compared.Multiple linear regression was used to evalu-ate the association between H-EPVS and cognitive function.Results Compared with the T2DM patients with normal cognition,the cognitive impairment had significantly higher total H-EPVS counts(P=0.015),and worse performance of global cognitive function,processing speed,immediate memory and delayed recall(P＜0.05).After adjusting for confounding factors by multiple linear regres-sion,total H-EPVS were associated with global cognitive function and immediate memory.Conclusion The H-EPVS are correlated with global cognitive function and memory function in patients with T2DM.The H-EPVS may be used as an imaging marker of cog-nitive impairment in T2DM patients.

Objective:To construct a novel chimeric antigen receptor T (CAR-T) cell targeting CD138 and to investigate its cytotoxicity against myeloma cells.Methods:The hybridoma strain that can stably secrete the CD138 monoclonal antibody (mAb) was prepared and obtained through monoclonal antibody screening technology. The hybridoma strain cells were intraperitoneally injected into mice to produce ascites containing monoclonal antibodies, which were then collected and purified to obtain pure CD138 mAb. Further examinations were performed to assess the biological characteristics of CD138 mAb. The variable region sequence of this antibody was amplified through reverse transcription polymerase chain reaction and was used as the antigen recognition domain of CD138 CAR, which was subsequently expressed on the surface of T cells by lentiviral infection. Flow cytometry was employed to assess the phenotype of CD138 CAR-T cells. In vitro cytotoxicity and degranulation assays were performed to evaluate their antitumor effects.Results:① We successfully prepared anti-human CD138 antibody hybridoma cell lines and screened a hybridoma cell strain, 5G2, which could persistently and stably secrete the anti-CD138 antibody. ② The purified CD138 (5G2) mAb can especially recognize CD138 + cells with a binding affinity constant (K D) of 6.011×10 -9 mol/L and showed no significant binding activity with CD138 - cells. ③The variable region sequence of the CD138 (5G2) antibody was obtained using molecular cloning technology, and CD138 (5G2) CAR was successfully constructed and expressed on T cells through lentivirus infection and, concurrently, demonstrated effective binding to recombinant human CD138 protein.④ The proliferation of T cells transduced with the CD138 (5G2) CAR was highly efficient. The phenotype analysis revealed that CD138 (5G2) CAR-T cells exhibited a greater tendency to differentiate into central memory T cells and memory stem T cells, with a reduced proportion of terminally differentiated effector memory subsets. ⑤CD138 (5G2) CAR-T cells demonstrated specific cytotoxicity against CD138 + myeloma cell line H929, whereas CD138 - cell line K562 remained unaffected. The percentage of residual H929 cells was (12.92±8.02) % after co-culturing with CD138 (5G2) CAR-T cells, while (54.25±15.79) % was left in the Vector-T group (E∶T=1∶2; P<0.001). ⑥Results of degranulation assays demonstrated a significant activation of CD138 (5G2) CAR-T cells after co-culture with the H929 cell line, whereas no significant activation was observed in Vector-T cells [ (25.78±3.35) % vs (6.13±1.30) %, P<0.001]. ⑦After co-culturing with CD138 + cells, CD138 (5G2) CAR-T cells exhibited a significant increase in cytokine secretion compared to the Vector-T group [interleukin-2: (1 697.52±599.05) pg/ml vs (5.07±1.17) pg/ml, P<0.001; interferon-γ: (3 312.20±486.38) pg/ml vs (9.28±1.46) pg/ml, P<0.001; and tumor necrosis factor-α: (1 837.43±640.49) pg/ml vs (8.75±1.65) pg/ml, P<0.001]. However, no significant difference was observed in cytokine secretion levels between the two groups after co-culturing with CD138 - cells. Conclusion:This study successfully prepared a novel monoclonal antibody against CD138, and CAR-T cells constructed with the antigen recognition domain derived from this 5G2 mAb demonstrated effective antitumor activity against myeloma cells. This can be used as a new option for the detection of the CD138 antigen and proposes a novel strategy for multiple myeloma immunotherapy.

Traditional pig breeding has a long cycle and high cost, and there is an urgent need to use new technologies to revitalize the pig breeding industry. The recently emerged CRISPR/Cas9 genome editing technique shows great potential in pig genetic improvement, and has since become a research hotspot. Base editor is a new base editing technology developed based on the CRISPR/Cas9 system, which can achieve targeted mutation of a single base. CRISPR/Cas9 technology is easy to operate and simple to design, but it can lead to DNA double strand breaks, unstable gene structures, and random insertion and deletion of genes, which greatly restricts the application of this technique. Different from CRISPR/Cas9 technique, the single base editing technique does not produce double strand breaks. Therefore, it has higher accuracy and safety for genome editing, and is expected to advance the pig genetic breeding applications. This review summarized the working principle and shortcomings of CRISPR/Cas9 technique, the development and advantages of single base editing, the principles and application characteristics of different base editors and their applications in pig genetic improvement, with the aim to facilitate genome editing-assisted genetic breeding of pig.
Animals ; Swine/genetics* ; Gene Editing ; CRISPR-Cas Systems/genetics* ; DNA Breaks, Double-Stranded

For the quality control of cetomacrogol 1000, a gas chromatographic method for the determination of residual impurities in cetomacrogol 1000, such as ethylene oxide, 1, 4-dioxane, ethylene glycol, diethylene glycol and triethylene glycol, was established and validated.The DB-1 column with headspace injection was used to detect ethylene oxide and 1, 4-dioxane with the inlet temperature of 150 °C, the FID temperature of 250 °C, the headspace equilibration temperature of 70 °C and the equilibration time of 45 min.The VF-17MS column with liquid injection was used to detect ethylene glycol, diethylene glycol and triethylene glycol with the inlet temperature of 270 °C, and the FID temperature of 290 °C.The results showed that ethylene oxide and 1,4-dioxane have a good linearity within their specified addition amount ranges (r > 0.999), with the RSD of precision of below 8.0% and the average recovery rates of 90.6% and 101.2%; and that ethylene glycol, diethylene glycol and triethylene glycol also have a good linearity between 3 ? 60 μg/mL (r > 0.999), with the RSD of precision of below 3.0%, and the recovery rates of 96% ~ 103%.The method established in this study has good specificity, linearity, precision and recovery rate, which can effectively detect the multi-component and trace impurities.

Objective:To investigate the strategy and feasibility of surgery for iatrogenic perforation of colorectum following colonoscopic examination or treatment.Methods:A retrospectively descriptive study was conducted. Twenty-one patients aged from 35 to 84 years old from the Department of General Surgery of the First Affiliated Hospital of Nanjing Medical University between Jan. 2015 and Dec. 2020 were enrolled in this study. There were 15 male and 6 female patients with a median age of 64 years.Observation indicators included patient demographics, including sex, age, comorbidity, abdominal surgical history; findings and outcomes of colonoscopy, including purpose of colonoscopy, time to the diagnosis of perforation; findings and outcomes of surgical treatment, including perforation site, perforation size, surgical methods, postoperative complications.Results:Eight patients were found with diagnostic colonoscopic perforation, 13 patients with therapeutic perforation (2 patients with endoscopic mucosal resection, 7 patients with endoscopic submucosal dissection and 4 patients with stent placement). Thirteen perforation occurred during the procedure of colonoscopy. Eleven patients with perforation occurred in the sigmoid colon, 3 in the ascending colon, 3 in the rectum, 2 in the descending colon, 1 in the cecum and 1 in the hepatic flexure. The perforation size ranged from 0.3 cm to 10.0 cm with a high likelihood of a bigger perforation occurred in diagnostic colonoscopy than therapeutic colonoscopy. Seven patients received primary surgical repair with 3 patients receiving diversion. Four patients received direct colostomy in the perforation site. Six patients received segmental colectomy or radical resection with primary anastomosis, among them 2 patients received defunctioning ileostomy. Four patients received resection with the Hartmann procedure. Nine patients were performed with laparoscopic surgery with 3 patients converted to open surgery. Six patients developed postoperative complications, including 1 bowel leakage, 2 wound infection, 1 wound infection accompanied with abdominal infection, 1 kidney infection. One patient with hepatic flexure perforation after stent placement died from septic shock after the Hartmann procedure.Conclusion:With proper indication, the performance of optimal surgical treatment will save lives of patients with colonoscopic perforation.

Objective:To analyze the anatomical distribution of complex facial injuries (woun-ds ≥8 cm in length and involving two or more anatomical areas) in children, and to explore the effect of plastic and aesthetic surgery.Methods:A total of 157 children with complex facial injury were admitted to the Plastic Surgery Department of Hangzhou Plastic Surgery Hospital from January 2019 to June 2021, including 94 males and 63 females, aged from 2 to 18 years, with an average age of 6.2 years. The wound length was 8-20 cm, with an average length of 10.3 cm. Plastic surgery techniques were used to design different primary repair schemes according to specific wound conditions, and early postoperative scar prevention and treatment were carried out.Results:In 157 cases, 331 anatomical areas were involved, most of which were buccal (75 sites). The injury caused by sharp instruments (glass, ceramic tile, cutting tools, etc.) ranked the first place with 78 cases. All patients were followed up for more than 3 months, and the results showed 146 cases of primary healing, 11 cases of delayed healing, 8 cases of scar hyperplasia, 149 cases of good morphological and functional recovery.Conclusions:The advantages of using plastic and cosmetic surgery techniques to treat complex facial injuries lie in the emphasis on anatomical and functional reduction and tension-reducing suture, combined with a variety of postoperative scar prevention and treatment measures, and the results are satisfactory.