OBJECTIVE To evaluate the efficacy and safety of amoxicillin combined with proton pump inhibitor （PPI） or potassium-competitive acid blocker （P-CAB） for Helicobacter pylori （Hp） eradication. METHODS Randomized controlled trial （RCTs） on amoxicillin combined with PPI or P-CAB for Hp eradication were retrieved from PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang， and VIP data. The search time frame was from database inception to September 5， 2025. After literature screening， data extraction， and quality assessment， a network meta-analysis was performed using Stata 17.0 software. RESULTS A total of 12 RCTs involving 5 515 patients were included， encompassing 8 therapeutic regimens： PPI combined with high-dose amoxicillin for 14 days （TR1）， PPI combined with low-dose amoxicillin for 14 days （TR2）， P-CAB combined with high-dose amoxicillin for 7 days （TR3）， P-CAB combined with high-dose amoxicillin for 14 days （TR4）， P-CAB combined with high-dose amoxicillin for 10 days （TR5）， P-CAB combined with low-dose amoxicillin for 7 days （TR6）， P-CAB combined with low-dose amoxicillin for 14 days （TR7）， and P-CAB combined with low-dose amoxicillin for 10 days （TR8）. The network meta-analysis results showed that， in terms of intention-to-treat Hp eradication rates， the eradication rates of TR5 and TR4 were significantly higher than those of TR3， TR8， TR6 and TR1 （ P ＜0.05）. The surface under the cumulative ranking curve （SUCRA） values from highest to lowest were： TR4 （89.7%）＞TR5 （82.3%）＞TR7 （71.5%）＞ TR2 （48.6%）＞TR1 （43.9%）＞TR8 （28.7%）＞TR3 （22.7%）＞TR6 （12.6%）. Regarding safety， the incidence of adverse reactions in TR3 and TR5 was significantly lower than that in TR1 （ P ＜0.05）. The SUCRA values from highest to lowest were： TR1 （91.3%）＞TR4 （79.8%）＞TR5 （55.0%）＞TR7 （50.9%）＞TR8 （41.3%）＞TR2 （36.4%）＞TR3 （27.6%） ＞TR6 （17.7%）. CONCLUSIONS Although the regimen of P-CAB combined with high-dose amoxicillin for 14 days demonstrates the best efficacy， the combination of P-CAB with high-dose amoxicillin for 10 days exhibits a better balanced profile in terms of both efficacy and safety.

OBJECTIVE: To establish and validate a novel diabetic retinopathy (DR) risk-prediction model using a whole-exome sequencing (WES)-based machine learning (ML) method. METHODS: WES was performed to identify potential single nucleotide polymorphism (SNP) or mutation sites in a DR pedigree comprising 10 members. A prediction model was established and validated in a cohort of 420 type 2 diabetic patients based on both genetic and demographic features. The contribution of each feature was assessed using Shapley Additive explanation analysis. The efficacies of the models with and without SNP were compared. RESULTS: WES revealed that seven SNPs/mutations ( rs116911833 in TRIM7, 1997T>C in LRBA, 1643T>C in PRMT10, rs117858678 in C9orf152, rs201922794 in CLDN25, rs146694895 in SH3GLB2, and rs201407189 in FANCC) were associated with DR. Notably, the model including rs146694895 and rs201407189 achieved better performance in predicting DR (accuracy: 80.2%; sensitivity: 83.3%; specificity: 76.7%; area under the receiver operating characteristic curve [AUC]: 80.0%) than the model without these SNPs (accuracy: 79.4%; sensitivity: 80.3%; specificity: 78.3%; AUC: 79.3%). CONCLUSION Novel SNP sites associated with DR were identified in the DR pedigree. Inclusion of rs146694895 and rs201407189 significantly enhanced the performance of the ML-based DR prediction model.
Diabetic Retinopathy/diagnosis* ; Humans ; Machine Learning ; Male ; Female ; Polymorphism, Single Nucleotide ; Middle Aged ; Exome Sequencing ; Aged ; Adult ; Pedigree ; Diabetes Mellitus, Type 2/complications* ; Genetic Predisposition to Disease ; Mutation

Objective:To analyze the electrocardiogram (ECG) data of congenital long QT syndrome (LQTS) patients, and to identify the ECG parameters for prediction of life-threatening arrhythmic events (LAEs).Methods:This cohort study enrolled patients diagnosed with congenital LQTS at the Department of Cardiology, Beijing Tsinghua Changgung Hospital from September 2014 to May 2023. Baseline clinical and ECG data were collected. Patients were followed with LAEs as the primary endpoint. Based on the occurrence of LAEs, patients were divided into two groups: the event group and the event-free group. Cox regression analysis was used to identify independent predictors of LAEs in LQTS patients.Results:A total of 293 patients diagnosed with congenital LQTS were included, aged 32.5 (19.0, 41.8) years, including 201 females (68.6%). Sixty-six patients experienced LAEs and 227 patients did not. Compared to the event-free group, the event group had a younger onset age (13.0 (5.5, 20.5) years vs. 26.0 (13.0, 35.0) years), a slower heart rate (69.0 (59.5, 76.5) beats/min vs. 77.0 (67.0, 88.0) beats/min), a higher proportion with family history of sudden cardiac death (30.3% vs. 14.5%), as well as longer QT intervals (500.0 (467.0, 594.0) ms vs. 428.0 (402.0, 470.0) ms) and QTc intervals (544.0 (502.5, 589.0) ms vs. 489.0 (480.0, 504.0) ms). Additionally, the event group had higher peak T-wave alternans value (65.0 (42.5, 85.3) μV vs. 44.0 (36.0, 54.0) μV), a higher proportion of patients with documented torsades de pointes (TdP) or ventricular fibrillation (VF) on 24-hour Holter monitoring (39.3% vs. 4.9%), and higher rates of pharmacological treatment (100.0% vs. 9.7%) and device therapy or left cardiac sympathetic denervation (45.5% vs. 2.2%) (all P<0.05). Multivariate Cox regression analysis identified that the heart rate<60 beats/min ( HR=2.0, 95% CI: 1.0-3.7) and QTc interval ≥500 ms ( HR=2.9, 95% CI: 1.5-5.6) on 12-lead ECG, as well as peak T-wave alternans value ≥55.5 μV ( HR=3.2, 95% CI: 1.3-7.8) and documented TdP or VF ( HR=2.0, 95% CI: 1.1-3.7) on 24-hour Holter monitoring were independent predictors of LAEs in LQTS patients (all P<0.05). Conclusion:Heart rate <60 beats/min and QTc interval ≥500 ms on 12-lead ECG, along with peak T-wave alternans value ≥55.5 μV and documented TdP or VF on 24-hour Holter monitoring, have been identified as independent predictors of LAEs in patients with LQTS. These ECG parameters may serve as valuable early indicators of sudden cardiac death in LQTS patients.

Objective:To analyze the electrocardiogram (ECG) data of congenital long QT syndrome (LQTS) patients, and to identify the ECG parameters for prediction of life-threatening arrhythmic events (LAEs).Methods:This cohort study enrolled patients diagnosed with congenital LQTS at the Department of Cardiology, Beijing Tsinghua Changgung Hospital from September 2014 to May 2023. Baseline clinical and ECG data were collected. Patients were followed with LAEs as the primary endpoint. Based on the occurrence of LAEs, patients were divided into two groups: the event group and the event-free group. Cox regression analysis was used to identify independent predictors of LAEs in LQTS patients.Results:A total of 293 patients diagnosed with congenital LQTS were included, aged 32.5 (19.0, 41.8) years, including 201 females (68.6%). Sixty-six patients experienced LAEs and 227 patients did not. Compared to the event-free group, the event group had a younger onset age (13.0 (5.5, 20.5) years vs. 26.0 (13.0, 35.0) years), a slower heart rate (69.0 (59.5, 76.5) beats/min vs. 77.0 (67.0, 88.0) beats/min), a higher proportion with family history of sudden cardiac death (30.3% vs. 14.5%), as well as longer QT intervals (500.0 (467.0, 594.0) ms vs. 428.0 (402.0, 470.0) ms) and QTc intervals (544.0 (502.5, 589.0) ms vs. 489.0 (480.0, 504.0) ms). Additionally, the event group had higher peak T-wave alternans value (65.0 (42.5, 85.3) μV vs. 44.0 (36.0, 54.0) μV), a higher proportion of patients with documented torsades de pointes (TdP) or ventricular fibrillation (VF) on 24-hour Holter monitoring (39.3% vs. 4.9%), and higher rates of pharmacological treatment (100.0% vs. 9.7%) and device therapy or left cardiac sympathetic denervation (45.5% vs. 2.2%) (all P<0.05). Multivariate Cox regression analysis identified that the heart rate<60 beats/min ( HR=2.0, 95% CI: 1.0-3.7) and QTc interval ≥500 ms ( HR=2.9, 95% CI: 1.5-5.6) on 12-lead ECG, as well as peak T-wave alternans value ≥55.5 μV ( HR=3.2, 95% CI: 1.3-7.8) and documented TdP or VF ( HR=2.0, 95% CI: 1.1-3.7) on 24-hour Holter monitoring were independent predictors of LAEs in LQTS patients (all P<0.05). Conclusion:Heart rate <60 beats/min and QTc interval ≥500 ms on 12-lead ECG, along with peak T-wave alternans value ≥55.5 μV and documented TdP or VF on 24-hour Holter monitoring, have been identified as independent predictors of LAEs in patients with LQTS. These ECG parameters may serve as valuable early indicators of sudden cardiac death in LQTS patients.

Sucrose synthase plays a crucial role in the plant sugar metabolism pathway by catalyzing the production of uridine diphosphate (UDP)-glucose, which serves as a bioactive glycosyl donor for various metabolic processes. In this study, a sucrose synthase gene named CtSus was cloned from Cistanche tubulosa, a traditional Chinese medicine known for its rich content of diverse glycosides, based on transcriptome analysis results. The open reading frame of CtSus was 2 418 bp long encoding 805 amino acids. Sequence analysis revealed conserved domains associated with the plant sucrose synthase family at both the N-terminal and C-terminal regions of CtSus protein. Phylogenetic analysis demonstrated that CtSus shares a close evolutionary relationship with sucrose synthases from other plants within the same order. Functional identification of CtSus was performed through whole-cell catalysis coupling with UGT71BD1, a characterized glycosyltransferase enzyme. The results showed that the introduction of CtSus significantly enhanced the conversion rate of glycosylation catalyzed by UGT71BD1. The soluble expression of CtSus in Escherichia coli was further achieved using the pCold^TM TF expression vector. In vitro enzymatic assay indicated the activity of CtSus to catalyze the formation of UDP-glucose in the presence of sucrose and UDP. Real-time quantitative-polymerase chain reaction results showed that the expression patterns of CtSus gene in different parts of C. tubulosa and the suspension cell cultures of C. tubulosa under drought stress correlated with the accumulation patterns observed for phenylethanol glycosides, respectively. Furthermore, key amino acids and their interactions between enzyme and substrate were explored based on protein structure prediction and molecular docking results. Overall, our findings identify a sucrose synthase CtSus responsible for the supply of the active glycosyl donor UDP-glucose during the biosynthesis of glycoside products in C. tubulosa and have also provided a gene element that can be utilized in engineering strain construction for glycoside products production.

ObjectiveTranscription factor NFE2 was observed abnormal expression in myeloproliferative neoplasm (MPN) patients. However, how NFE2 is transcriptionally regulated remains ambiguous. This study aims to explore the elements and molecular mechanisms involved in the transcriptional regulation of NFE2. MethodsActive enhancers were predicted by public NGS data and conformed experimentally via dual luciferase reporter assay. After that, PRO-seq and GRO-seq data was used to detect enhancer RNAs transcribed from these enhancers. RACE was utilized to clone the full length enhancer RNA (eRNA) transcripts, and RT-qPCR was used to measure their expression in different leukemia cell lines as well as the transcript levels during induced differentiation. Finally, to investigate the molecular function of the eRNA, overexpression and knockdown of the eRNA via lentivirus system was performed in K562 cells. ResultsWe identified three enhancers regulating NFE2 transcription, which located at -3.6k, -6.2k and +6.3k from NFE2 transcription start site (TSS) respectively. At the -3.6k enhancer, we cloned an eRNA transcript and characterized that as a lncRNA which was expressed and located in the nucleus in three types of leukemia cell lines. When this lncRNA was overexpressed, expression of NFE2 was upregulated and decreases of K562 cell proliferation and migration ability were observed. While knocking down of this lncRNA, the level of NFE2 decreases correspondingly and the proliferation ability of K562 cells increases accordingly. ConclusionWe identified an enhancer lncRNA that regulates NFE2 transcription positively and suppresses K562 cell proliferation.

Objective To explore the antimicrobial activity of antiparasitic drug dichlorophenol(DIC)against Staphylococcus aureus(S.aureus).Methods Antimicrobial susceptibility and resistance inducing ability of S.au-reus against DIC was detected by micro-broth dilution assay and disc diffusion test;bactericidal efficacy of DIC was assessed by time-killing curve;inhibitory effect of DIC on the formation of biofilm and eradicating of formed biofilm of S.aureus was detected by crystal violet and XTT staining;cytotoxicity of DIC was detected by cell counting kit-8(CCK-8),and a mouse model of skin abscess infection was constructed to detect the in vivo antimicrobial activity and toxicity of DIC.Results The minimal inhibitory(MIC)and minimal bactericidal concentration(MBC)of DIC against S.aureus standard strains were 2-4 μg/mL and 2-8 μg/mL,respectively.The MIC and MBC of DIC against S.aureus clinical strains were 2-8 μg/mL and 8-32 μg/mL,respectively.Disc diffusion test indicated the obvious concentration-dependent bacterial growth inhibitory effects of DIC on S.aureus standard strains.Time-killing assay revealed that DIC concentration of 4 × MIC was found to reduce the viable bacterial cells of S.aureus standard strains ATCC 29213 and ATCC 43300 from(5.51±0.27)Log10 CFU/mL and(5.44±0.08)Log10 CFU/mL to the limit of detection after 2 hours and 4 hours treatment,respectively.No drug-resistant mutant strains of S.aureus were found after 15 consecutive passage of DIC with subinhibitory concentration on bacteria.2 μg/mL DIC could significantly inhibit the formation of S.aureus biofilm and reduce the total amount of biofilm from(100±7.49)％to(11.12±2.86)％(P＜0.001).2 μg/mL DIC significantly eradicated the formed S.aureus biofilm and reduced the total biofilm from(100±10.34)％to(42.53±16.87)％(P＜0.001).DIC could significantly reduce the viable bac-terial load of S.aureus in abscess in mice,and reduce the number of viable bacteria from(9.54±0.46)Log10 CFU/abscess to(7.78±0.62)Log10 CFU/abscess(P＜0.05).Hematoxylin-eosin staining result showed that DIC could significantly reduce the abscess area and inflammatory cell infiltration in mice tissue,and was well tolerated in vivo.Conclusion DIC has low cytotoxicity and obvious in vitro and in vivo antimicrobial activity,which is expected to be an alternative treatment for drug-resistant S.aureus infection.

Objective To explore the antimicrobial activity of antiparasitic drug dichlorophenol(DIC)against Staphylococcus aureus(S.aureus).Methods Antimicrobial susceptibility and resistance inducing ability of S.au-reus against DIC was detected by micro-broth dilution assay and disc diffusion test;bactericidal efficacy of DIC was assessed by time-killing curve;inhibitory effect of DIC on the formation of biofilm and eradicating of formed biofilm of S.aureus was detected by crystal violet and XTT staining;cytotoxicity of DIC was detected by cell counting kit-8(CCK-8),and a mouse model of skin abscess infection was constructed to detect the in vivo antimicrobial activity and toxicity of DIC.Results The minimal inhibitory(MIC)and minimal bactericidal concentration(MBC)of DIC against S.aureus standard strains were 2-4 μg/mL and 2-8 μg/mL,respectively.The MIC and MBC of DIC against S.aureus clinical strains were 2-8 μg/mL and 8-32 μg/mL,respectively.Disc diffusion test indicated the obvious concentration-dependent bacterial growth inhibitory effects of DIC on S.aureus standard strains.Time-killing assay revealed that DIC concentration of 4 × MIC was found to reduce the viable bacterial cells of S.aureus standard strains ATCC 29213 and ATCC 43300 from(5.51±0.27)Log10 CFU/mL and(5.44±0.08)Log10 CFU/mL to the limit of detection after 2 hours and 4 hours treatment,respectively.No drug-resistant mutant strains of S.aureus were found after 15 consecutive passage of DIC with subinhibitory concentration on bacteria.2 μg/mL DIC could significantly inhibit the formation of S.aureus biofilm and reduce the total amount of biofilm from(100±7.49)％to(11.12±2.86)％(P＜0.001).2 μg/mL DIC significantly eradicated the formed S.aureus biofilm and reduced the total biofilm from(100±10.34)％to(42.53±16.87)％(P＜0.001).DIC could significantly reduce the viable bac-terial load of S.aureus in abscess in mice,and reduce the number of viable bacteria from(9.54±0.46)Log10 CFU/abscess to(7.78±0.62)Log10 CFU/abscess(P＜0.05).Hematoxylin-eosin staining result showed that DIC could significantly reduce the abscess area and inflammatory cell infiltration in mice tissue,and was well tolerated in vivo.Conclusion DIC has low cytotoxicity and obvious in vitro and in vivo antimicrobial activity,which is expected to be an alternative treatment for drug-resistant S.aureus infection.

Objective:To evaluate the preoperative localization value of endoscopic ultrasound guided fine needle tattooing (EUS-FNT) for laparoscopic distal pancreatectomy in pancreatic lesions with a maximum diameter ≤3 cm.Methods:From November 2017 to October 2022, at the Second Affiliated Hospital of Soochow University, the data of patients with pancreatic lesions ≤3 cm who underwent laparoscopic distal pancreatectomy were retrospectively analyzed. Eight patients who underwent EUS-FNT assisted laparoscopic distal pancreatectomy were included in the fine needle tattooing (FNT) combined laparoscopic group. And 14 patients who underwent simple laparoscopic distal pancreatectomy were taken as the simple laparoscopic group. The success rate and complications of EUS-FNT were observed. The differences in operation time, surgery-related complications and complete resection rate of lesions between the two groups were compared. Mann-Whitney U test and descriptive analysis were used for statistical analysis. Results:In the FNT combined laparoscopic group, the lesions of 4 cases were located in the pancreatic body and 4 cases in the pancreatic tail. In the simple laparoscopic group, the lesions of 4 cases were located in the pancreatic body and 10 cases in the pancreatic tail. There was a significant difference in lesion size between the two groups (14.5 mm (10.8 mm, 16.5 mm) vs. 27.0 mm (23.5 mm, 30.0 mm), Z=-3.09, P=0.001). In the FNT combined laparoscopic group, EUS-FNT was successfully performed in all 8 patients. The average time of laparoscopy after EUS-FNT was (98.4±8.8) min. The marks were clearly visible under the laparoscopic field of view, and no complications such as abdominal hemorrhage and hematoma were observed. Laparoscopic pancreaticocaudectomy was performed in 5 cases and pancreaticocaudectomy plus splenectomy in 3 cases. The median operation time was 192.5 min (176.3 min, 203.8 min). The amount of intraoperative bleeding was large in 2 patients and blood transfusion was needed. The lesions were one-time completely resected in all 8 patients. The postoperative pathology were 6 cases of pancreatic neuroendocrine neoplasm, 1 case of intraductal papillary mucinous neoplasm (IPMN), and 1 case of solid pseudopapilloma. In the simple laparoscopic group, laparoscopic pancreaticocaudectomy was performed in 2 cases and pancreaticocaudectomy plus splenectomy in 12 cases. The median operation time was 202.5 min (192.8 min, 235.0 min), which was longer than that of FNT combined laparoscopic group, but the difference was not statistically significant ( P>0.05). The amount of intraoperative bleeding was large in 2 patients and blood transfusion was needed. In 1 patient with pancreatic body lesions, no lesion was found in the specimen examination after the first pancreatectomy, and the lesions were completely resected after the second partial pancreatectomy. Active abdominal hemorrhage occurred in 1 patient on the second day after operation, and underwent interventional embolization for hemostasis. Two weeks after surgery, 1 patient was found to have a encapsulated fluid with a long diameter of 6 cm around the pancreas by computed tomography re-examination 2 weeks after surgery. The postoperative pathology were 5 cases of pancreatic neuroendocrine neoplasm, 2 cases of IPMN, 1 case of solid pseudopapilloma, 1 case of pancreatic cyst with glandular low-grade intraepithelial neoplasia, 1 case of ectopic spleen, and 4 cases of pancreatic ductal adenocarcinoma. Conclusion:EUS-FNT can effectively localize small pancreatic lesions before laparoscopic distal pancreatectomy, shorten the operation time and improve the complete resection rate under laparoscopy.

Electrical impedance tomography (EIT) is an emerging technology for real-time monitoring based on the impedance differences of different tissues and organs in the human body. It has been initially applied in clinical research as well as disease diagnosis and treatment. Lung perfusion refers to the blood flow perfusion function of lung tissue, and the occurrence and development of many diseases are closely related to lung perfusion. Therefore, real-time monitoring of lung perfusion is particularly important. The application and development of EIT further promote the monitoring of lung perfusion, and related research has made great progress. This article reviews the principles of EIT imaging, lung perfusion imaging methods, and their clinical applications in recent years, with the aim of providing assistance to clinical and scientific researchers.
Humans ; Electric Impedance ; Lung/physiology* ; Tomography, X-Ray Computed ; Perfusion ; Tomography/methods*