Objective To investigate the role of CCCTC-binding factor(CTCF)in the development of oxaliplatin(OXA)-induced gastric cancer drug-tolerant cells(DTCs)and to preliminarily elucidate its underlying mechanisms.Methods The DTCs model of gastric cancer was established by treating MGC803 cells with OXA.Overexpression and knockdown of CTCF in MGC803 cells were performed to observe their effects on the formation of DTCs in gastric cancer.Additionally,Bcl2-like protein 1(BCL2L1)was knocked down in CTCF-overexpressing cells,and its impact on DTCs formation was evaluated.Flow cytometry was used to analyze the effects of varying CTCF/BCL2L1 expression levels on the apoptosis of gastric cancer cells under OXA treatment.Immunohistochemistry(IHC)was employed to detect the expression levels of CTCF/BCL2L1 in gastric cancer tissues,and the therapeutic outcomes of neoadjuvant chemotherapy in patients with different CTCF/BCL2L1 expression levels were assessed.Results Gastric cancer DTCs can be obtained following a regimen of continuous treatment of MGC803 cells with a specific concentration of oxaliplatin(OXA,1.5 μmol/L)for 5 days,followed by an additional 5-day culture period post-treatment cessation.The upregulation of CTCF has been shown to facilitate the formation of DTCs in gastric cancer,whereas its downregulation inhibits this process(P<0.05).In MGC803 gastric cancer cells,the expression level of BCL2L1 is positively correlated with that of CTCF.Knockdown of BCL2L1 in MGC803 cells overexpressing CTCF can reverse the pro-DTC formation effect of CTCF(P<0.05).Overexpression of CTCF confers resistance to OXA-induced apoptosis in gastric cancer cells,and this anti-apoptotic effect can be reversed by BCL2L1 knockdown in MGC803 cells overexpressing CTCF(P<0.05).In the tumor tissues of the majority of gastric cancer patients,the expression levels of BCL2L1 are positively correlated with those of CTCF,and the efficacy of neoadjuvant chemotherapy is notably reduced in patients with high expression of the CTCF/BCL2L1 axis compared to those with low expression(P<0.05).Conclusion CTCF promotes the formation of OXA-related gas-tric cancer DTCs by upregulating BCL2L1 expression and inhibiting apoptosis,making the CTCF/BCL2L1 axis a potential therapeutic target for DTCs in gastric cancer.

AIM:To investigate the risk factors for intolerance to sacubitril/valsartan in the treatment of heart failure.METHODS:A total of 124 heart fail-ure patients hospitalized in our hospital from May 2023 to May 2024 were collected.Logistic regres-sion analysis and nomogram analysis were used to identify the risk factors for drug tolerance.RE-SULTS:22 patients exhibited intolerance,with low blood pressure being the primary cause(P<0.05).Multivariate regression analysis found that patients with a low BMI(OR 95%CI 1.814(1.385-2.525))and those without concomitant right heart failure(OR 95%CI 4.998(1.552-17.301))were more likely to ex-perience drug intolerance.The model had a stable C-index of 0.923(95%CI=0.863-0.975).CONCLU-SION:Low BMI and absence of right heart failure are risk factors affecting the tolerance to sacubitril/valsartan,which has certain value for guiding clini-cal treatment.Large-sample clinical studies are still needed to confirm these findings.

Objective:To understand the etiological surveillance and drug resistance characteristics of Legionella pneumophila (LP) from the aqueous environment of public places in Shanghai, from 2011 to 2020, and provide evidence for surveillance of the disease. Methods:Environmental water samples were systematically collected from public venues in urban and suburban districts of Shanghai for LP surveillance. All the identified LP isolates underwent a series of testings including serotyping, pulsed field gel electrophoresis (PFGE), sequence-based typing, and antimicrobial susceptibility testing. χ2 test or Cochran-Armitage trend tests were used for statistical analysis and for temporal resistance patterns. Results:Among 6 263 water samples, the LP-positive rate was 20.93% (1 311/6 263). The positivity rate decreased from 24.98% (287/1 149) in 2011-2012 to 20.02% (1 024/5 114) in 2013-2020 ( χ2=13.92, P<0.001), with the highest monthly positivity observed from June to August (23.79%, 745/3 132). A total of 1 365 LP strains were isolated, of which 912 were further characterized, including 10 serotypes, 149 PFGE patterns, and 33 sequence types (ST). The predominant serotype was Lp1 (86.84%, 792/912), and the dominant ST was ST752 (29.50%, 269/912). ST clustering revealed two major clonal groups CG1 and CG2, accounting for 91.12% (831/912) of the isolates. The 190 LPs involved in the drug sensitivity test showed three resistance profiles: azithromycin resistance (31.05%, 59/190), ciprofloxacin resistance (0.53%, 1/190) and azithromycin+ciprofloxacin resistance (0.53%, 1/190). Azithromycin-resistant strains were predominantly ST1 (64.41%, 38/59). The antimicrobial resistance rate showed a significant decline, from 48.65% (18/37) in 2011-2012 to 28.10% (43/153) in 2013-2020 ( χ2=9.38, P=0.002). Conclusions:Compared to from 2011 to 2012, both the positivity rate and antimicrobial resistance prevalence of LP in public aqueous environments of Shanghai exhibited an overall decline from 2013 to 2020. The predominant types of LP were serotype Lp1 and sequence type ST752, with notable high-level resistance to azithromycin. Measures as enhancing the enforcement of water safety regulations and prioritizing surveillance of azithromycin resistance in LP were recommended to mitigate public health risks.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To assess the preliminary efficacy and safety of modified Société Internationale d′Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.Methods:This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children′s Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.Results:Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively ( χ 2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively ( χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates ( χ2=5.36, 7.84, P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant ( χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid. Conclusions:The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

This study investigated the potential pathogenicity and genetic characteristics of ST314 Salmonella Kentucky(S.Ken-tucky)isolates from a broiler slaughterhouse.Antimicrobial susceptibility testing and whole-genome sequencing(WGS)were used to determine antimicrobial resistance,virulence factors,and the presence of antimicrobial resistance genes(ARGs)and mobile genetic elements(MGEs)among the isolates.The three multidrug resistant(MDR)isolates exhibited high resistance to multiple antimicrobial agents.The F4-2S strain exhibited resistance to 14 drugs across seven categories,whereas the F4T strain showed resistance to 13 drugs in the same number of categories.In contrast,the Y23 strain was resistant to nine drugs in six categories.Notably,F4-2S dem-onstrated high homology with F4T:both possessed 13 ARGs distributed across nine categories,in addition to a wide range of virulence factors,including secretion systems and effector proteins.The presence of IncR and IncX1 plasmids significantly enhanced both the antimicrobial resistance and pathogenicity of the isolates.The genome map of Y23 revealed a chromosome alongside two plasmids.The chromosome containedonly one resistance gene but several virulence factors,including the type III secretion system(T3SS),which is crucial for bacterial invasion.The plasmid pY23-1 contained eight types of 19 ARGs.Comparative analysis indicated that pY23-1 ex-hibited high homology with pZ1323SSL0055 and pSAL-045,all of which contained multiple ARGs,thus suggesting critical roles of these genes in the evolution of bacterial resistance.In conclusion,ST314 S.Kentucky demonstrated a complex mechanism of resis-tance coupled with significant pathogenic potential.The ARGs and MGEs in the plasmid contributed to the emergence and dissemina-tion of antimicrobial resistance.The multiple virulence factors present in the chromosome may be key factors driving the increasing virulence of ST314 S.Kentucky.

Objective To explore the application effect of 3D printed individualized model in the treatment of complex ankle fractures(AF).Methods Patients with complex AF admitted to our hospital from July 2021 to October 2022 were selected and divided into the control group and the observation group using a random number table method,with 50 cases in each group.Patients in the control group were received minimally invasive reduction and internal fixation,while these in the observation group were given minimally invasive reduction and internal fixation under the guidance of 3D printed individualized model.The surgical conditions,ankle joint reduction,stress indicators[norepinephrine(NE)and angiotensin Ⅱ(AngⅡ)],ankle function and postoperative complications were compared between the two groups.Results There were 2 patients in the observation group and 3 patients in the control group were lost to follow-up 12 months after surgery.Compared with the control group,the observation group showed a decrease in the intraoperative blood loss,shortened surgical time,hospitalization time,and weight-bearing activity time,and an increase in the anatomical reduction rate(P<0.05).The observation group had lower serum levels of NE and AngⅡ 1 and 3 days after surgery(P<0.05)and higher Kofoed score and American Orthopedic Foot and Ankle Society(AOFAS)scores 1,6,and 12 months after surgery(P<0.05),as well as lower incidence of postoperative complications(P<0.05)than those in the control group.Conclusion For the treatment of complex AF,3D printed individualized model assisted the formulation of minimally invasive reduction and fixation surgical plans before surgery can shorten surgical time,reduce stress injury,decrease the risk of complications,and simultaneously increase the anatomical reduction rate and improve ankle joint function,thereby accelerating postoperative recovery of patients.

Objective:To understand the etiological surveillance and drug resistance characteristics of Legionella pneumophila (LP) from the aqueous environment of public places in Shanghai, from 2011 to 2020, and provide evidence for surveillance of the disease. Methods:Environmental water samples were systematically collected from public venues in urban and suburban districts of Shanghai for LP surveillance. All the identified LP isolates underwent a series of testings including serotyping, pulsed field gel electrophoresis (PFGE), sequence-based typing, and antimicrobial susceptibility testing. χ2 test or Cochran-Armitage trend tests were used for statistical analysis and for temporal resistance patterns. Results:Among 6 263 water samples, the LP-positive rate was 20.93% (1 311/6 263). The positivity rate decreased from 24.98% (287/1 149) in 2011-2012 to 20.02% (1 024/5 114) in 2013-2020 ( χ2=13.92, P<0.001), with the highest monthly positivity observed from June to August (23.79%, 745/3 132). A total of 1 365 LP strains were isolated, of which 912 were further characterized, including 10 serotypes, 149 PFGE patterns, and 33 sequence types (ST). The predominant serotype was Lp1 (86.84%, 792/912), and the dominant ST was ST752 (29.50%, 269/912). ST clustering revealed two major clonal groups CG1 and CG2, accounting for 91.12% (831/912) of the isolates. The 190 LPs involved in the drug sensitivity test showed three resistance profiles: azithromycin resistance (31.05%, 59/190), ciprofloxacin resistance (0.53%, 1/190) and azithromycin+ciprofloxacin resistance (0.53%, 1/190). Azithromycin-resistant strains were predominantly ST1 (64.41%, 38/59). The antimicrobial resistance rate showed a significant decline, from 48.65% (18/37) in 2011-2012 to 28.10% (43/153) in 2013-2020 ( χ2=9.38, P=0.002). Conclusions:Compared to from 2011 to 2012, both the positivity rate and antimicrobial resistance prevalence of LP in public aqueous environments of Shanghai exhibited an overall decline from 2013 to 2020. The predominant types of LP were serotype Lp1 and sequence type ST752, with notable high-level resistance to azithromycin. Measures as enhancing the enforcement of water safety regulations and prioritizing surveillance of azithromycin resistance in LP were recommended to mitigate public health risks.

Objective The quality of compound menthol nasal drops was reviewed and analyzed,and identified the bad trend in time.The improvement measures were formulated to improve the quality of the preparation.Methods Taking camphor and menthol in compound menthol nasal drops of Beijing Shijitan Hospital,Capital Medical University,as indicators,the quality of 30 batches of samples was retrospectively analyzed using the capacity sixpack report.The failure mode and effect analysis(FMEA)were applied to the prospective quality risk management.Results All 30 batches of compound menthol nasal drops met the quality standards,and the process was under control.Howe ver,there were potential risks in the process of menthol,so risk management was carried out and improvement measures are formulated.Conclusion The compound menthol nasal drops of the hospital have stable quality,and the quality of the medicine can be continuously ensured with improved processes.