BACKGROUND:How to effectively promote bone regeneration and bone reconstruction after bone injury has always been a key issue in clinical bone repair research.The use of biological and degradable materials loaded with bioactive factors to treat bone defects has excellent application prospects in bone repair. OBJECTIVE:To investigate the effect of polylactic acid-glycolic acid copolymer(PLGA)composite scaffold modified by lysine-grafted graphene oxide nanoparticles(LGA-g-GO)on osteogenic differentiation and new bone formation. METHODS:PLGA was dissolved in dichloromethane and PLGA scaffold was prepared by solvent evaporation method.PLGA/GO composite scaffolds were prepared by dispersing graphene oxide uniformly in PLGA solution.LGA-g-GO nanoparticles were prepared by chemical grafting method,and the PLGA/LGA-g-GO composite scaffolds were constructed by blending LGA-g-GO nanoparticles at different mass ratios(1%,2%,and 3%)with PLGA.The micromorphology,hydrophilicity,and protein adsorption capacity of scaffolds of five groups were characterized.MC3T3 cells were inoculated on the surface of scaffolds of five groups to detect cell proliferation and osteogenic differentiation. RESULTS AND CONCLUSION:(1)The surface of PLGA scaffolds was smooth and flat under scanning electron microscope,while the surface of the other four scaffolds was rough.The surface roughness of the composite scaffolds increased with the increase of the addition of LGA-g-GO nanoparticles.The water contact angle of PLGA/LGA-g-GO(3%)composite scaffolds was lower than that of the other four groups(P<0.05).The protein adsorption capacity of PLGA/LGA-g-GO(1%,2%,and 3%)composite scaffolds was stronger than PLGA and PLGA/GO scaffolds(P<0.05).(2)CCK-8 assay showed that PLGA/LGA-g-GO(2%,3%)composite scaffold could promote the proliferation of MC3T3 cells.Alkaline phosphatase staining and alizarin red staining showed that the cell alkaline phosphatase activity in PLGA/LGA-g-GO(2%,3%)group was higher than that in the other three groups(P<0.05).The calcium deposition in the PLGA/GO and PLGA/LGA-g-GO(1%,2%,and 3%)groups was higher than that in the PLGA group(P<0.05).(3)In summary,PLGA/LGA-g-GO composite scaffold can promote the proliferation and osteogenic differentiation of osteoblasts,and is conducive to bone regeneration and bone reconstruction after bone injury.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Objective:Employing the cascade care model, this qualitative study explores determinants influencing the cascading care stages of hypertension and diabetes by interviewing various stakeholders.Methods:In July 2023, purposive sampling was employed to recruit participants from Gongyi and Wugang cities in Henan Province, and Linqu County in Weifang City, Shandong Province. Semi-structured in-depth interviews were conducted with representatives of policymakers, healthcare institution managers, providers, and patients with hypertension and diabetes.And thematic analysis was performed using both inductive and deductive approaches.Results:A total of 82 individuals were interviewed, with an age range of (53.8±12.0) years, among which 48 (58.5%) were male; including 5 policymakers, 10 institutional managers, 20 healthcare providers, and 47 patients with hypertension and diabetes. The study identified both barriers and facilitating factors at the patient, healthcare provider, and system levels across various stages: awareness, screening, diagnosis, treatment, long-term management, and control of hypertension and diabetes.Conclusion:By delineating and analyzing the barriers and facilitators at each stage of hypertension and diabetes care, this study lays the groundwork for the development of effective, feasible, and sustainable implementation pathways, with significant implications for the enhanced management of hypertension and diabetes in China.

Objective This study aimed to investigate the role and mechanism of atractylenolide Ⅰ in inhibiting XPOT proliferation and invasion in gastric cancer cells.Methods This study included exploration of XPOT expression in gastric cancer tissues,analysis of gene expression data from GC patients in TCGA and GEO databases,as well as various cellular assays to detect the ability of cancer cells to proliferate,migrate,and invade.Protein expression levels of XPOT,SKP2,CyclinA,and P27 mRNA were also detected by qPCR and Western Blot.Results Analysis confirmed that XPOT was highly expressed in gastric cancer tissues,indicating a poor prognosis.In vitro studies revealed that AT-1 inhibits the proliferation and invasion ability of GC cells;XPOT down-regulation also inhibits these abilities.Furthermore,AT-1 down-regulates the expression of XPOT which then regulates SKP2,P27,and CyclinA-ultimately inhibiting the proliferation and invasion of gastric cancer cells through the regulation of the XPOT pathway.Conclusion The overexpression of XPOT in gastric cancer tissues can indicate a poor prognosis.Atractylenolide Ⅰ down-regulates the XPOT-regulated ubiquitination-proteasome pathway to inhibit proliferation and invasion of gastric cancer cells.

Objective:Employing the cascade care model, this qualitative study explores determinants influencing the cascading care stages of hypertension and diabetes by interviewing various stakeholders.Methods:In July 2023, purposive sampling was employed to recruit participants from Gongyi and Wugang cities in Henan Province, and Linqu County in Weifang City, Shandong Province. Semi-structured in-depth interviews were conducted with representatives of policymakers, healthcare institution managers, providers, and patients with hypertension and diabetes.And thematic analysis was performed using both inductive and deductive approaches.Results:A total of 82 individuals were interviewed, with an age range of (53.8±12.0) years, among which 48 (58.5%) were male; including 5 policymakers, 10 institutional managers, 20 healthcare providers, and 47 patients with hypertension and diabetes. The study identified both barriers and facilitating factors at the patient, healthcare provider, and system levels across various stages: awareness, screening, diagnosis, treatment, long-term management, and control of hypertension and diabetes.Conclusion:By delineating and analyzing the barriers and facilitators at each stage of hypertension and diabetes care, this study lays the groundwork for the development of effective, feasible, and sustainable implementation pathways, with significant implications for the enhanced management of hypertension and diabetes in China.

Objective To explore the potential pathogenic genes of intestinal metaplasia.Methods Twenty-one patients with intestinal metaplasia admitted to the Department of Gastroenterology at the Second Affiliated Hospital of Anhui University of Chinese Medicine from January,2022 to June,2022,and 21 healthy subjects undergoing gastroscopic examination during the same period were enrolled in this study.All the participants underwent gastroscopy and pathological examination,and gastric tissue samples were collected for transcriptome sequencing to screen for differentially expressed genes(DEGs).The biological functions of the DEGs were analyzed using bioinformatics analysis,and qRT-PCR was used to validate the results.Results Transcriptomic sequencing identified a total of 1373 DEGs,including 827 upregulated and 546 downregulated ones.The top 6 upregulated genes(AGMAT,CCL25,FABP1,CDX1,SPINK4,and MUC2),ranked based on their significance and average expression level,were selected for validation,and qRT-PCR showed significant upregulation of their mRNAs in the gastric tissues of patients with intestinal metaplasia(P<0.05).Conclusion AGMAT,CCL25,FABP1,CDX1,SPINK4,and MUC2 participate in the occurrence and development of intestinal metaplasia,and may serve as potential biomarkers for diagnosing intestinal metaplasia.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

The American College of Gastroenterology Guidelines:Management of Acute Pancreatitis(referred to as the"2024 guidelines"),released in March 2024,presents 11 recommendations and 23 key concepts for the management of acute pancreatitis(AP)based on different levels of evidence quality.The 2024 guidelines provide detailed explanations regarding the diagnostic criteria,etiology,initial assessment,severity stratification,initial management,endoscopic retrograde cholangiopancreatography,antibiotic use,nutritional support,and surgical interventions for AP.Compared to the 2023 edition of the American College of Gastroenterology Guidelines,the 2024 edition offers more detailed recommendations and comprehensive evidence-based medical data,which is of great significance in optimizing the diagnosis and treatment process for AP patients and improving patient outcomes.

Objective To explore the potential pathogenic genes of intestinal metaplasia.Methods Twenty-one patients with intestinal metaplasia admitted to the Department of Gastroenterology at the Second Affiliated Hospital of Anhui University of Chinese Medicine from January,2022 to June,2022,and 21 healthy subjects undergoing gastroscopic examination during the same period were enrolled in this study.All the participants underwent gastroscopy and pathological examination,and gastric tissue samples were collected for transcriptome sequencing to screen for differentially expressed genes(DEGs).The biological functions of the DEGs were analyzed using bioinformatics analysis,and qRT-PCR was used to validate the results.Results Transcriptomic sequencing identified a total of 1373 DEGs,including 827 upregulated and 546 downregulated ones.The top 6 upregulated genes(AGMAT,CCL25,FABP1,CDX1,SPINK4,and MUC2),ranked based on their significance and average expression level,were selected for validation,and qRT-PCR showed significant upregulation of their mRNAs in the gastric tissues of patients with intestinal metaplasia(P<0.05).Conclusion AGMAT,CCL25,FABP1,CDX1,SPINK4,and MUC2 participate in the occurrence and development of intestinal metaplasia,and may serve as potential biomarkers for diagnosing intestinal metaplasia.

Objective:To investigate the clinical effect of surgical treatment of concealed penis based on the idea of flap transfer in the treatment of hypospadias.Methods:Retrospectively analyzed the clinical data of children with concealed penis admitted to the Urology Department of Chengdu Second People’s Hospital and Department of Pediatric Surgery at Children’s Medical Center of Sichuan Provincial People’s Hospital, from July 2017 to July 2021. The control group used the traditional surgical method and the experimental group used a modified surgical approach based on the idea of flap transfer in the treatment of hypospadias. Short-term complications such as flap ischemia, edema, and skin dehiscence were statistically analyzed in the two groups, as well as the Boemers rating of penile appearance (good, general, poor), Vancouver scar scale (VSS) (mild, moderate, severe), overall penis shape (tower, cylindrical, inverted tower) at 6 months after surgery. Count data were analyzed using the Chi-square test.Results:298 children, aged 2.5 to 13.7 years, with a mean age of 6.4 years, were enrolled in the study. 103 children were in the control group, and 195 children were in the experimental group. All enrolled patients were operated successfully in the first stage and were discharged 3-4 days after the operation, with an average recovery time of 3-4 weeks. After a follow-up of more than 6 months, in the control group, 2 cases (1.9%) of flap ischemia and 3 cases (2.9%) of skin dehiscence occurred after surgery. Two children (1.0%) in the experimental group had skin dehiscence after surgery, and the difference in the recent complication rate between the two groups was not significant [4.9%(5/103) vs. 1.0%(2/195), P>0.05]. The proportion of Boemers rated"good"in the experimental group was higher than that in the control group [93.3% (182/195) vs. 71.8% (74/103), P<0.01]. The proportion of moderate to severe scarring assessed by VSS was lower in the experimental group than in the control group [6.2% (12/195) vs. 26.2% (27/103), P<0.01]. The proportion of the overall penis shape of the penis close to the cylindrical shape of the normal penis in the experimental group was significantly higher than that in the control group [81.5% (159/195) vs. 60.2% (62/103), P<0.01]. Conclusion:Compared with the traditional surgical method, the modified surgical approach based on the idea of flap transfer in the treatment of hypospadias attaches more importance to the overall planning of the flap and the tension distribution of the fascial layer, which can be more effective to solve the problem of insufficient coverage of the concealed penile skin and reduce postoperative scar formation. Moreover, the appearance of the external genitalia is natural and closer to normal, the surgical effect is exact, and the long-term postoperative complications are lower.