ObjectiveTo analyze the distribution, drug resistance characteristics, and changing trends of Acinetobacter baumannii (AB) isolated from environmental surfaces and healthcare workers’ hands in a grade Ⅱ level A general hospital in Xuhui District of Shanghai from 2018 to 2023, and to provide reference for infection control in the hospital. MethodsEnvironmental samples were collected quarterly from critical surfaces and healthcare workers’ hands in the intensive care unit (ICU), geriatrics, and respiratory departments from 2018 to 2023. Clinical isolates were obtained from all patients with AB infections in ICU, geriatrics, respiratory department, rehabilitation department, infectious diseases department, emergency department, cardiology department, and orthopedics of the hospital from 2018 to 2023. Retrospective analyses were performed on AB detection rates, strain origins, resistance rates to commonly used antimicrobial agents, and resistance gene features, comparing the antimicrobial resistance between clinically isolated strains and environmentally isolated strains. ResultsFrom 2018 to 2023, a total of 1 416 samples were collected from the hospital and a total of 272 strains of AB were detected, with a positive detection rate of 19.21%. The detection rate gradually decreased year-on-year (χ²_trend=45.290, P<0.001). The majority of samples originated from patient-contacted items (34.56%, 94/272), followed by shared items (26.84%, 73/272) and healthcare worker-contacted items (15.07%, 41/272). From 2018 to 2023, the resistance rate of AB on environmental surfaces and healthcare workers’ hands to commonly tested antibiotics in the hospital ranged from 10% to 40%. The resistance rates to cefotaxime (42.52%) and piperacillin (38.58%) were relative high, while the resistance to polymyxin E (1.57%), polymyxin B (2.36%), and doxycycline (3.94%) maintained low. The annual fluctuations in resistance to cefotaxime, piperacillin, ceftriaxone, tobramycin, doxycycline, minocycline and cotrimoxazole were statistically significant (all P<0.05). There were statistically significant differences in the resistance of clinical and environmental isolates to ampicillin/sulbactam, cefepime, ceftazidime, subamphetamine, meropenem, piperacillin, aztreonam, gentamicin, tobramycin, minocycline, ciprofloxacin, levofloxacin, and cotrimoxazole in the hospital from 2018 to 2023 (all P<0.05). The resistance rate of clinical isolates was generally high, especially to β-lactam and quinolone drugs, which were mostly above 80% [such as cefepime (93.86%), cefotaxime (97.37%), imipenem (98.25%), and ciprofloxacin (99.12%)]. The resistance rate of environmental isolated strains to similar antibiotics was relatively lower, mostly concentrated at 10%‒30%. The whole-genome sequencing of 34 carbapenem-resistant Acinetobacter baumannii (CRAB) strains isolated from the hospital environment in 2023 revealed that the main resistance mechanism was overexpression of efflux pumps (51.97%), followed by changes in target sites (32.46%). Among the 34 CRAB strains, carbapenem resistance genes OXA-23 and OXA-51 were detected in 6 strains (17.65%), while genes such as KPC, IMP, VIM, and SIM were not detected. ConclusionFrom 2018 to 2023, AB in the hospital environment exhibited high resistance rates to certain antimicrobial agents and carried multiple resistance genes, indicating a potential transmission risk. It is necessary to further strengthen bacterial resistance monitoring and hospital infection control, and use antibiotics reasonably.

The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus, lipid metabolism disorders, atherosclerosis and inhibit inflammation. Since the pathogenesis of heart failure with preserved ejection (HFpEF) is multifactorial and closely associated with the aforementioned diseases, we aim to study the effect of nitazoxanide on high-fat diet (HFD) plus L-NAME (N ω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice. We found that oral nitazoxanide improved cardiac hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, increased blood pressure, impaired exercise tolerance, impaired glucose handling, serum lipid disorders, hepatic steatosis, increased weight of white adipose tissues and kidney fibrosis in HFD + L-NAME-treated mice. In the established HFD + L-NAME-induced HFpEF and metabolic syndrome mouse model, therapeutic treatment with nitazoxanide rescued HFD + L-NAME-induced pathological phenotypes as mentioned above. The in vitro experiments revealed that tizoxanide, the active metabolite of nitazoxanide, increased the basal mitochondria metabolism of cardiomyocytes, inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts, and relaxed phenylephrine- and U46619-induced constriction of rat mesenteric arteries, indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo. The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Bladder cancer （BCa） is the most common malignant tumor of the urinary system， and its incidence is increasing year by year. At present， for all patients with resectable non-metastatic muscle-invasive BCa， radical cystectomy + bilateral pelvic lymph node dissection is strongly recommended， but they still face the risk of recurrence， metastasis and death. In recent years， the proportion of patients with advanced and metastatic BCa is increasing among patients with newly diagnosed BCa. Although current treatment models are diverse， they often struggle to achieve significant efficacy due to their low effectiveness and adverse effects， resulting in low survival rates for patients with advanced and metastatic BCa. Therefore， the treatment of BCa still faces great challenges， and there is an urgent need to discover an effective new antitumor drug. With the improvement of medical standards， traditional Chinese medicine has shown great advantages in the treatment of BCa. Traditional Chinese medicine is mild and easy to accept， and can inhibit tumor progression through a multi-pathway， multi-way and multi-target manner， so as to exert its anticancer effect. Taraxaci Herba is a medicinal and food homologous plant， which has many biological activities， such as antibacterial， anti-inflammatory， anti-oxidation， anti-tumor， protecting liver and gallbladder， reducing blood sugar and enhancing immunity， and it has shown a clear anticancer effect in breast cancer， liver cancer， gastric cancer， tongue cancer and lung cancer. By reviewing previous studies worldwide， this article summarizes the mechanism of Taraxaci Herba extract in inducing autophagy and apoptosis， inhibiting cell migration and invasion， regulating cell cycle and proliferation， regulating cell metabolism， inhibiting tumor angiogenesis， combining the effects of chemotherapeutic drugs， and regulating the transduction of related signal pathways. On this basis， this study systematically elaborates on the potential mechanism of Taraxaci Herba against BCa， in order to provide a theoretical basis for the research and treatment of BCa.

AIM:To analyze the expression changes of O-linked N-acetylglucosamine(O-GlcNAc)glycoprotein in the lens capsule of age-related cataract and diabetic cataract and investigate the role of O-GlcNAc glycoprotein in diabetic cataract.METHODS: The lens capsules of 54 patients(56 eyes)with diabetic cataract and 115 patients(120 eyes )with age-related cataract were studied. Immunoblotting was used to detect the expression level of O-GlcNAc protein in the lens capsules of age-related and diabetic cataracts, and mass spectrometry was used to identify the O-GlcNAc glycoproteins in lens capsules.RESULTS: Immunoblotting results showed that the expression level of O-GlcNAc protein in the lens capsule of diabetic cataracts was significantly higher than in the age-related cataracts(P<0.01). With the level of glycosylated hemoglobin increasing, the expression level of O-GlcNAc protein also increased(P<0.01). Totally 5 O-GlcNAc proteins with up-regulated expression(FABP5, KRT16, PGK1, CTSD and S100A7), and 18 O-GlcNAc proteins with down-regulated expression(CRYβB1, etc.)were identified in the lens capsule of patients with diabetic cataract by mass spectrometry. Three new O-GlcNAc glycosylation sites were identified in this study. They were O-GlcNAcylation at T1730 position and S1738 position of PTPRQ and O-GlcNAcylation at T61 position of ATP5MC2.CONCLUSION:O-GlcNAc glycosylation may be involved in the formation and development of diabetic cataract. The differential O-GlcNAc glycoprotein identified by mass spectrometry provided the data for further study about pathogenesis of diabetic cataract.

Objective To investigate and evaluate the nutrition status in serum 25-hydroxy vitamin D[25(OH)D]levels of 0～12 years old children in Xi'an.Methods A total of 2 670 patients aged 0～12 years old who underwent routine physical examinations in Children's Health Department of the Second Hospital of Air Force Medical University were selected from March 2020 to July 2023,and the 25(OH)D data of these patients were conducted in retrospective analysis.The nutritional status of vitamin D in these children of different genders,ages and seasons were also analyzed.Results ①This study included 2 670 children aged 0～12 years old in Xi'an,with the average level of serum 25(OH)D was 40.80±18.00 ng/ml.Among them,38 cases(1.42%)had serum 25(OH)D deficiency,333 cases(12.47%)had serum 25(OH)D insufficience,and 2 299 cases(86.11%)had sufficient serum 25(OH)D.②There was a statistically significant difference in serum 25(OH)D levels among different age groups(H=1 524.23,P=0.000).The group aged 1～<4 has the highest value of 52.51±13.57 ng/ml,while the group aged 8～12 has the lowest value of 21.65±6.75 ng/ml.③The levels of serum 25(OH)D in summer(39.44±17.46 ng/ml)were lower than those in spring(41.96±17.76 ng/ml)and autumn(42.71±18.15 ng/ml),with statistical significant differences(Z=101.57,-134.06,all P<0.01).However,the deficiency and inadequate rate of serum 25(OH)D in winter(18.95%)was higher than those in spring,summer and autumn(13.52%,12.75%,12.36%),with statistical significant differences(χ2=14.32,P=0.026).④There was no statistically significant difference in serum 25(OH)D levels between genders(H=0.933,P=0.351).However,the deficiency and inadequate rate of serum 25(OH)D in boys(12.51%)was lower than that in girls(15.46%),and the difference was statistically significant(χ2=9.257,P=0.010).Conclusion The nutritional status of serum 25(OH)D in children aged 0～12 years in Xi'an area is comparatively fine,and it is necessary to strengthen the intake and supplementation of vitamin D in over 3 years old children.

Objective:To explore the effect of intervention model based on comprehensive nutrition management on glucose and lipid metabolism and pregnancy outcome in patients with gestational diabetes mellitus (GDM).Methods:104 GDM patients admitted to Shanxi Bethune Hospital from February 2022 to March 2023 were randomly divided into control group and experimental group, with 52 cases in each group. The control group implemented routine management measures and nutrition guidance, while the experimental group implemented an intervention model based on comprehensive nutrition management on the basis of routine management. The indexes of glucose and lipid metabolism (glycosylated hemoglobin, fasting blood glucose, 2 h postprandial blood glucose, total cholesterol, triglyceride and low density lipoprotein cholesterol), pregnancy outcome, self-management ability and self-efficacy were compared between the two groups before and after intervention.Results:Before the intervention, there was no significant difference in general situation, glucose and lipid metabolism index, self-management ability and self-efficacy between the two groups ( P>0.05). After the intervention, the level of glucose and lipid metabolism index in the experimental group was significantly lower than that in the control group, with statistical significance ( P<0.05). The incidence of adverse pregnancy outcome in the experimental group was significantly lower than that in the control group, with statistical significance ( P<0.05). The scores of self-management ability and self-efficacy in the experimental group were significantly higher than those in the control group, with statistical significance ( P<0.05). Conclusion:The intervention model based on comprehensive nutrition management can effectively improve the glucose and lipid metabolism index and pregnancy outcome of GDM patients, and significantly improve their self-management ability and self-efficacy related to nutrition management, which has high clinical application and promotion value.

The nasal swab samples of swine influenza(SI)suspected pigs were collected and tested for H3 subtype swine influenza virus(SIV)positive by RT-qPCR.The positive samples were inoc-ulated into SPF chicken embryos for virus isolation.The full genome sequencing and sequence anal-ysis of the isolated H3N2 subtype SIV were conducted,and its pathogenicity was studied.The re-sults showed that a strain of SIV was successfully isolated and identified as H3N2 subtype by RT-PCR,named A/Swine/Yunnan/KM/06/2023(H3N2).The BLSAT results showed that the eight segments of SIV H3N2 KM had the highest homology with eight different strains of swine influ-enza or human influenza viruses,reaching 95.41％-97.49％.The HA and NA segments were de-rived from H3N2 subtype SIV,the NP segment was derived from H1N1 subtype human influenza virus,the M segment was derived from H1N2 subtype SIV,and all other segments were derived from H1N1 subtype SIV.The key receptor sites(190D,223V,226I,228S)of HA protein remained unchanged.The pathogenicity experiment results showed that infected piglets exhibited symptoms such as fever,sneezing,runny nose,the virus could be detoxified to the outside through the nasal cavity,and the lungs had different degrees of lesion.Immunohistochemistry(IHC)showed that the virus could replicate in the lungs.In conclusion,a strain of H3N2 subtype SIV was successfully iso-lated,and the genetic evolution,molecular characteristics and pathogenicity of the virus were stud-ied.It revealed that H3N2 subtype SIV is constantly evolving and had pathogenicity to piglets,pro-viding a reference for monitoring and preventing SIV epidemics in China,and provided a candidate strain for SI vaccine development.

Objective:To investigate the clinical efficacy of arthroscopic modified anatomic glenoid reconstruction with Enden-Hybinette procedure combined with loop plate fixation in the treatment of recurrent anterior dislocation of shoulder combined with severe glenoid bone loss.Methods:A retrospective case series study was conducted to analyze 36 patients with recurrent anterior dislocation of the shoulder combined with severe glenoid bone loss who were admitted to 901st Hospital of the Joint Logistics Support Force of PLA from January 2019 to January 2021, including 28 males and 8 females, aged 18-33 years [(29.5±3.0)years]. All the patients had injury history. The dislocation frequency range was 2-40 times [(20.5±6.5)times]. Beighton scale scores were 3-9 points [(4.0±0.8)points]. All the patients underwent anatomic reconstruction of the glenoid bone with arthroscopic modified Enden-Hybinette procedure using iliac autograft and loop plate elastic fixation. Posterior glenoid version angle, the breadth of the glenoid cavity and the A-P glenoid cavity depth were measured and osseous anatomy of the reconstructed glenoid bone was evaluated. Union of the Iliac bone block and glenoid bone loss was observed and the absorption rate of the bone block was evaluated at 6 months after surgery. The shoulder stability score, functional activity score, joint range of motion score and total Rowe score of shoulder function were used to evaluate the shoulder stability, functional activity and movement before surgery, at 3, 6 months after surgery and at the last follow-up. The incidence of complications was observed.Results:All the patients were followed up for 12-24 months [(18.8±3.5)months]. At 1, 3, 6 months after surgery and at the last follow-up, posterior glenoid version angle was (11.3±1.7)°, (10.6±1.2)°, (9.1±2.0)° and (9.2±1.9)° respectively; the breadth of the glenoid cavity was (34.2±1.3)mm, (33.2±1.0)mm, (32.2±1.0)mm and (31.3±1.1)mm respectively; the A-P glenoid cavity depth was (2.6±0.1)mm, (2.4±0.1)mm, (2.3±0.2)mm and (2.2±0.2)mm respectively, which were all significantly improved compared with those before surgery [(-5.9±1.0)°, (24.3±1.2)mm and (0.6±0.1)mm respectively] ( P<0.01), with no significant differences among those at different postoperative time points ( P>0.05). Bony union was observed in the iliac bone block and glenoid bone loss after bone grafting in all the patients at 6 months after surgery and the iliac bone block resorption rate was (20.5±4.1)%. At 3, 6 months after surgery and at the last follow-up, the shoulder stability score was (41.5±6.1)points, (43.9±6.3)points and (44.7±5.0)points respectively; the functional activity score was (26.9±2.5)points, (27.1±2.5)points and (28.6±2.3)points respectively; the joint range of motion score was (13.9±1.0)points, (14.9±1.2)points and (15.8±1.5)points respectively; the total Rowe score of shoulder function was (81.4±11.5)points, (85.8±12.3)points and (86.4±9.8)points respectively, which were significantly improved compared with those before surgery [(6.1±1.5)points, (11.9±1.5)points, (8.5±1.4)points and (27.4±7.5)points respectively] ( P<0.01), with no significant differences among those at different postoperative time points ( P>0.05). At the follow-up, no complications such as incision infection, neurological injuries, implant failure of displacement, recurrent re-dislocation of the shoulder or osteoarthritis were observed. Conclusion:Arthroscopic modified anatomic glenoid reconstruction with Enden-Hybinette procedure combined with loop plate fixation in the treatment of recurrent anterior dislocation of shoulder combined with severe glenoid bone loss has the advantages of better osseous anatomy of the reconstructed glenoid bone, better bony union, satisfactory shoulder stability, functional restoration, etc.

Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6～8 weeks old and weighing from 180～220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.