BACKGROUND: Owing to the high prevalence of antibiotic resistance in Helicobacter pylori ( H. pylori ) in China, bismuth-containing quadruple therapies have been recommended for H. pylori eradication. This study compared the efficacy and safety of quadruple regimens containing vonoprazan vs . esomeprazole for H. pylori eradication in a patient population in China. METHODS: This was a phase 3, multicenter, randomized, double-blind study. Patients with confirmed H. pylori infection were randomized 1:1 to receive quadruple therapy for 14 days: amoxicillin 1000 mg and clarithromycin 500 mg after meals, bismuth potassium citrate 600 mg before meals, plus either vonoprazan 20 mg or esomeprazole 20 mg before meals, all twice daily. The primary outcome was the eradication rate of H. pylori , evaluated using a 13 C urea breath test at 4 weeks after treatment. The non-inferiority margin was at 10%. RESULTS: The study included 510 patients, 506 of whom completed the follow-up assessment. The primary analysis revealed eradication rates of 86.8% (210/242) and 86.7% (208/240) for vonoprazan and esomeprazole therapy, respectively (treatment difference: 0.1%; 95% confidence interval [CI]: -5.95, 6.17; non-inferiority P  = 0.0009). Per-protocol analysis showed eradication rates of 87.4% for vonoprazan and 86.3% for esomeprazole (treatment difference: 1.2%; 95% CI: -5.03, 7.36; non-inferiority P  = 0.0004). Vonoprazan and esomeprazole were well tolerated, with similar safety profiles. CONCLUSION: Vonoprazan was found to be well-tolerated and non-inferior to esomeprazole for eradicating H. pylori in patients from China. TRIAL REGISTRATION ClinicalTrials.gov , NCT04198363.
Humans ; Esomeprazole/therapeutic use* ; Double-Blind Method ; Helicobacter Infections/drug therapy* ; Male ; Female ; Middle Aged ; Helicobacter pylori/pathogenicity* ; Pyrroles/therapeutic use* ; Sulfonamides/therapeutic use* ; Adult ; Clarithromycin/therapeutic use* ; Amoxicillin/therapeutic use* ; Aged ; Anti-Bacterial Agents/therapeutic use* ; Pyrrolidines/therapeutic use* ; Drug Therapy, Combination ; Proton Pump Inhibitors/therapeutic use*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Metastatic lung cancer continues to cause a high number of deaths due to high malignancy and poor prognosis, and the efficacy of typical chemotherapy or immunotherapy is less than ideal due to the low pulmonary accumulation and targeting of therapeutics. Here, a submicron-sized biomimetic liposome was formulated for the lung-targeted co-delivery of bacterial superantigen and paclitaxel. Recombinant staphylococcal enterotoxin C2 (rSEC2), a bacterial superantigen, was expressed with the Escherichia coli system and showed potent immunostimulatory activities to mediate tumor cell death. The submicron-sized (∼800 nm) biomimetic liposomes, namely 4T1 cell membrane-hybrid rSEC2 paclitaxel liposomes (TSPLs), exhibited high lung-accumulation efficiency and tumor homologous effect due to the suitable particle size and membrane hybridization of cancer cell membranes with phospholipids. Intravenous TSPLs remarkably inhibited metastatic lung cancer with limited systemic immune responses. TSPLs reversed the immunosuppressive state and increased the proportion of local CD4⁺ and CD8⁺ T cells in the lung; moreover, paclitaxel increased tumor cell apoptosis and reduced tumor burden. In summary, the high lung cancer targeting was achieved by particle size control and cell membrane hybridization, and the highly efficient anticancer effect was achieved by the co-delivery of superantigens and chemotherapeutic drugs.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

OBJECTIVE: We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers. METHODS: The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort (TGOC) between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories. RESULTS: FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory ( P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [ OR] = 1.90, 95% confidence interval [ CI]: 1.17-3.10; OR = 2.21, 95% CI: 1.09-4.45). CONCLUSION An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Humans ; Male ; Adult ; Blood Glucose/analysis* ; China ; Prospective Studies ; Occupational Exposure/adverse effects* ; Risk Factors ; Middle Aged ; Steel ; Fasting/blood* ; Metal Workers ; East Asian People

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To investigate the effect of nuclear receptor subfamily 2 group F member 2(NR2F2)on the biological behaviors of human ovarian cancer SKOV3 cells,and to clarify its molecular mechauism and provide the new idea for treatment of ovarian cancer.Methods:Gene Expression Profiling Interactive Analysis(GEPIA)Database analyse the expression level of NR2F2 gene in ovarian tissue,and analyse its correlation with clinical prognosis of ovarian cancer patients.The human ovarian cancer SKOV3 cells were divided into control group and NR2F2 over-expression(NR2F2 OE)group,which were transfected with mCherry control virus and NR2F2 OE over-expression virus,respectively,when the cell deusity reached 70％,and the stable transfection SKOV3 cell lines were screened with puromycin(puro)48h lafter.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the transfection efficiencies of the cells;RT-qPCR method was used to detect the expression levels of NR2F2 and sex-determining region Y-box 2(SOX2)mRNA in the cells in two groups;Western blotting method was used to detect the expression levels of NR2F2,ATP-binding cassette superfamily G member 2(ABCG2),and programmed cell death 1-ligand 1(PD-L1)protcins in the cells in two groups.CCK-8 assay was used to detect the proliferation activities of the cells in two groups;Wound assay was used to detect the migration rates of the cells in two groups;Transwell chamber assay was used to detect the number of transmembrane cells;Spheroidization assay was used to detect the numbers of spheroids in the cells;peripheral blood mononuclear cells(PBMCs)-mediated tumor cell killing assay was used to detect the relative densities of surviving tumor cells;CCK-8 assay was used to detect the half maximal inhibitory concentration(IC50)of paclitaxel(PTX)and carboplatin(CBP).Results:Compared with normal ovarian tissue,the expression level of NR2F2 gene in ovarian tumor tissue was decreased(P＜0.05),and decreased with the improvement of clinical pathological grading of ovarian tumor.The patients with higher expression level of NR2F2 gene had better clincal prognosis.The SKOV3 cells with NR2F2 over-expresson were successfully constructed,and the expression levels of NR2F2 mRNA and protein in the cells in NR2F2 OE group were increased compared with control group(P＜0.001).The CCK-8 assay results showed that compared with control group,the proliferation activities of the cells in NR2F2 OE group were decreased at different time points(1,2,3,and 4 d)(P＜0.05 or P＜0.01).The cell wound assay results showed that compared with control group,the migration rate of the cells in NR2F2 OE group was decreased(P＜0.001).The Transwell assay results showed that compared with control group,the number of transmembrane cells in NR2F2 OE group was decreased(P＜0.01).Compared with control group,the number of the spheroids in NR2F2 OE group was decreased(P＜0.05),and the expression levels of SOX2 mRNA(P＜0.01)and protein(P＜0.001)were increased.Compared with control group,the relative density of surviving tumor cells in NR2F2 OE group was decreased,but the difference was not significant(P＜0.05),and the expression level of PD-L1 protein was decreased(P＜0.05).Compared with control group,the proliferation activities of cells in NR2F2 OE group were decreased(P＜0.05),and the drug sensitivities of the cells to PTX and CBP were enhanced(P＜0.05);the IC50 of PTX was significantly reduced,while the IC50of CBP could not be calculated due to excessively high drug concentration;the expression level of ABCG2 protein was decreased(P＜0.05).Conclusion:The over-expression of NR2F2 may inhibit the proliferation,migration,and invasion of the human ovarian cancer SKOV3 cells,decrease the expression levels of SOX2,PD-L1 and ABCG2 proteins,suppress the stemness and immune evasion ability of the SKOV3 cells,and enhance the sensitivities of the SKOV3 cells to PTX and CBP.

The Hedgehog(HH)signaling pathway is involved in various developmental processes of vertebrates and invertebrates,including embryogenesis,stem cell renewal,tissue regeneration,the occurrence and development of tumor and chemotherapy resistance.Overactivation and abnormal expression of key components in the HH signaling pathway are associated with the development of various malignant tumors.Phosphorylation plays an important role in regulating the activity and function of proteins in normal cells,and the disorder of phosphorylation-dephosphorylation cascade is closely related to tumorigenesis.The abnormal activation of this signaling pathway is also related to protein phosphorylation,while its complex underlying mechanism needs to be further explored.This article reviewed the research progress of the HH signaling pathway and protein phosphorylation modification in malignant tumors,focusing on the regulatory effect of phosphorylation modification on the activity of HH signaling pathway and its effect on the occurrence and development of malignant tumors,in order to provide a theoretical basis for the in-depth development and clinical application of targeted drugs for phosphatase/dephosphatase.

Objective:To discuss the effect of long non-coding RNA(lncRNA)LINC00973 on the migration,invasion,and distant metastasis of epithelial ovarian cancer,and to clarify its molecular mechanism.Methods:The human ovarian cancer SKOV3 and OVCAR3 cells were divided into EF1a-FH empty vector control group(control group),LINC00973 overexpression group(LINC00973 OE group),U6-shRNA empty vector control group(SHV group),and LINC00973 knockdown group(LINC00973 KD group),and were transfected with lentivirus containing nonsense sequence(pLent-EF1a-FH-CMV-copGFP-P2A-Puro),LINC00973 overexpression,nonsense sequence(pLent-U6-shRNA-CMV-copGFP-P2A-Puro)and LINC00973 shRNA,respectively,followed by puromycin screening to obtain stably transfected SKOV3 and OVCAR3 cells.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of target genes in the cells in various groups;wound healing assay was used to detect the migration rate of the cells in various groups;Transwell chamber assay was used to detect the number of transmembrane cells in various groups;The mice were divided into control group(WT group),LINC00973 OE group,and LINC00973 KD group,with 4 mice in each group.SKOV3 wild-type cells,LINC00973 OE cells,and LINC00973 KD cells were intraperitoneally injected into the mice in various groups,respectively,to establish the epithelial ovarian cancer intraperitoneal implantation and metastasis model;HE staining was used to observe the morphology of the colon and liver tissues of the mice in various groups;RNA-secquencing(RNA-seq)was used to analyze the differentially expressed genes between SHV and LINC00973 KD groups in the SKOV3 cell line;RT-qPCR method was used to detect the mRNA expression levels of LINC00973 in the normal ovarian epithelial cells IOSE-80 and epithelial ovarian cancer cells SKOV3,A2780 and OVCAR3,the mRNA expression levels of LINC00973,Vimentin,Snail family transcriptional repressor 1(Snail),Twist family basic helix-loop-helix transcription factor 1(Twist),zinc finger E-box binding homeobox 1(ZEB1),zinc finger E-box binding homeobox 2(ZEB2),CXCL8 and matrix metalloproteinase(MMP)16 in the cells in various groups,and the mRNA expression levels of LINC00973,Vimentin and Twist in liver and colon tissues of the mice in various groups.Results:Compared with normal ovarian epithelial cells IOSE-80,the expression level of LINC00973 mRNA in the epithelial ovarian cancer cells SKOV3,OVCAR3 and A2780 was significantly increased(P<0.01),with the highest expression level of LINC00973 in SKOV3 and OVCAR3 cells,which were therefore selected for subsequent experiments.In SKOV3 and OVCAR3 cells,compared with control group,the expression level of LINC00973 mRNA in the cells in LINC00973 OE group was increased(P<0.01);compared with SHV group,the expression level of LINC00973 mRNA in the cells in LINC00973 KD group was decreased(P<0.05 or P<0.01),indicating successful construction of LINC00973 overexpression and knockdown cell lines.In SKOV3 cells,compared with control group,the mRNA expression levels of Vimentin and Twist in LINC00973 OE group were increased(P<0.05 or P<0.01),while no significant difference was observed in Snail mRNA expression level(P>0.05);compared with SHV group,the mRNA expression levels of Vimentin,Snail and Twist in LINC00973 KD group were decreased(P<0.01).In OVCAR3 cells,compared with control group,the mRNA expression levels of Vimentin,Snail and Twist in LINC00973 OE group were increased(P<0.01);compared with SHV group,the expression levels of Vimentin,Snail,and mRNA Twist in LINC00973 KD group were decreased(P<0.01).The wound healing assay results showed that compared with control group,the wound healing rates of the SKOV3 and OVCAR3 cells in LINC00973 OE group were significantly increased(P<0.01);compared with SHV group,the wound healing rates of the cells in LINC00973 KD group were significantly decreased(P<0.01).The Transwell chamber assay results showed that compared with control group,the numbers of transmembrane cells of the SKOV3 and OVCAR3 cells in LINC00973 OE group were significantly increased(P<0.01);compared with SHV group,the numbers of transmembrane cells in LINC00973 KD group were significantly decreased(P<0.01).Compared with WT group,the number of peritoneal nodules in LINC00973 OE group was increased,with rough liver surface and multiple nodules formed on mesentery and colon surface,and the expression levels of LINC00973,Vimentin,and Twist mRNA in colon tissue were increased(P<0.01);compared with WT group,no nodules were formed in the peritoneal cavity of LINC00973 KD group,with smooth liver surface,no nodules in liver tissue,and decreased expression levels of LINC00973,Vimentin,and Twist mRNA,and no nodules were observed on mesentery and colon surface.The HE staining results showed that compared with WT group,the multiple lesions were observed in liver and colon tissues in LINC00973 OE group,manifested as uneven cell size,irregular shape,unclear cell boundaries,increased nuclear division,and uneven red staining in cytoplasm,while in LINC00973 KD group,the cells in liver and colon tissues were arranged neatly with regular shape,and uniform distribution of nuclei and cytoplasm.The RNA-seq results showed that compared with SHV group,no key signaling pathways related to tumor metastasis were enriched in LINC00973 KD group,and the transcription levels of metastasis-related genes CXCL8,MMP16,ZEB1,and ZEB2 were decreased.The RT-qPCR results showed that compared with control group,the expression levels of ZEB1,ZEB2,CXCL8,and MMP16 mRNA in the cells in LINC00973 OE group were significantly increased(P<0.01);compared with SHV group,the expression levels of ZEB1,ZEB2,CXCL8,and MMP16 mRNA in the cells in LINC00973 KD group were significantly decreased(P<0.01).Conclusion:LINC00973 can up-regulate the expression of metastasis-related factors Vimentin,Snail,Twist,ZEB1,ZEB2,CXCL8,and MMP16,and promote the migration,invasion,and distant metastasis of epithelial ovarian cancer.

Objective To investigate the epidemiological characteristics of Mycoplasma pneumoniae(MP)infection among pediatric inpatients with respiratory tract infections(RTIs)at Children's Hospital of Hebei Province,providing evidence for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on 79 546 children hospitalized for RTIs between January 2016 and February 2024.Nasopharyngeal aspirates or deep sputum samples were collected,and polymerase chain reaction(PCR)was used to detect nucleic acids of 13 respiratory pathogens,including MP and adenovirus.The epidemiological trends across different years,seasons,genders,and age groups were analyzed.Results Among the 79 546 enrolled cases(male:47 437,59.6%;female:32 109,40.4%),the MP-positive rate was 17.7%(14 106/79 546),peaking in 2023(28.8%)and reaching the lowest in 2021(7.0%).Except for the period from July 2020 to March 2021 with exceptionally low MP positivity,epidemic peaks consistently occurred between August and February or March of the following year.Seasonal analysis revealed significantly higher MP positivity in autumn and winter compared to spring(P<0.001).Female children exhibited a higher MP-positive rate(20.1%,6444/32 109)than males(16.2%,7662/47 437)(P<0.001).The MP-positive rate increased with age:infancy(3.2%,849/26 741),toddlerhood(9.3%,1935/20 763),preschool(21.2%,3918/18 448),and school-age(54.5%,7404/13 594)(P<0.001).Co-infections with other respiratory pathogens were observed in 37.3%(5264/14 106)of MP-positive cases,with human rhinovirus(HRV)being the most frequent co-pathogen(43.3%,2279/5264 of mixed infections).Conclusion MP is a major pathogen of RTIs in hospitalized children at Children's Hospital of Hebei Province.Infections occur year-round but predominantly in autumn,with higher susceptibility in females and school-age children.Targeted preventive measures should be implemented during peak seasons to mitigate transmission risks.