Antibiotic resistance is spreading at a faster rate than new antibiotic agents applied for clinical remedies. It is an urgent need to discover potential compounds to combat multidrug-resistant (MDR) bacteria. Marine fungi offer a promising avenue for mining antibiotic-like molecules with chemical diversity. To discover structurally novel and antibiotic metabolites, we screened the in-house marine fungus genome library and found a fungus Stephanonectria keithii LZD-10-1 containing a non-ribosomal peptide synthetase (NRPS) cluster with 18 modules to synthesize a new subfamily of peptaibols with effective eradication against MDR pathogens. Targeting isolation of the cultured fungus afforded six new peptaibols, which exhibit the ability to kill MDR bacteria by targeting bacterial membrane phospholipids, especially phosphatidylglycerol (PG), leading to the dysfunction of bacterial membranes. Furthermore, their efficacies against methicillin-resistant Staphylococcus aureus (MRSA) in both Galleria mellonella and mouse wound infection models were observed. This study underscores the significance of employing genome-guided approaches to identify untapped marine fungi as potential sources for novel antibiotic candidates with unique scaffolds.

Avian infectious bronchitis(IB),a rapidly spreading and acute disease in chickens,is caused by the infectious bronchitis virus(IBV).IB is characterized by its remarkable genetic varia-bility.IBV has a high degree of mutation,and the existing means of immunization often fail to a-chieve good results,seriously affecting the development of the domestic poultry industry.This ar-ticle offers a comprehensive review of the current understanding of the immune response to IBV,focusing on three key areas:non-specific immunity,mucosal immunity,and specific immunity.By dissecting these aspects,the aim is to provide a theoretical reference for the study of the immune mechanism of IBV.

Objective To establish a pediatric rare disease catalog,analyze the current status of therapeutic drugs and their coverage of the medical insurance in China,and propose strategies to enhance drug accessibility.Methods Pediatric rare diseases were identified from China's two national rare disease catalogs combined with the EU Orphanet database,US FDA orphan drug database,and the Diagnosis and Treatment Standards for Rare Diseases in Children.We created a specialized drug catalog for pediatric rare diseases,then analyzed drug types(ATC classification),pricing,and medical insurance coverage using descriptive statistics based on Yaozhi.com drug bidding prices and the 2024 Drug of List National Basic Medical Insurance(NBMIDL).Drug affordability was assessed through annual treatment cost calculations.Results The national catalogs included 151 pediatric rare diseases(72.95%of listed conditions),spanning 13 disease systems.We identified 94 dedicated orphan drugs(by generic name)for these conditions,among which 43 were approved internationally but unavailable in China.The average unit price per package was 6 113.53 yuan.Overall NBMIDL coverage was 68.83%,but drugs priced above 7 000 yuan per unit had only 7.69%coverage.Annual treatment costs reached 4.54 million for laronidase(mucopolysaccharidosis).Conclusions Critical gaps persist in China's pediatric rare disease treatment landscape,including catalog deficiencies,inadequate coverage for high-cost drugs and insufficient domestic innovation.It is recommended to establish a list of orphan drugs for pediatric rare diseases,accelerate the import of foreign drugs and the local innovative drugs through policy incentives,optimizing medical insurance reimbursement mechanisms for pediatric rare disease drugs to comprehensively improve therapeutic accessibility.

Avian infectious bronchitis(IB),a rapidly spreading and acute disease in chickens,is caused by the infectious bronchitis virus(IBV).IB is characterized by its remarkable genetic varia-bility.IBV has a high degree of mutation,and the existing means of immunization often fail to a-chieve good results,seriously affecting the development of the domestic poultry industry.This ar-ticle offers a comprehensive review of the current understanding of the immune response to IBV,focusing on three key areas:non-specific immunity,mucosal immunity,and specific immunity.By dissecting these aspects,the aim is to provide a theoretical reference for the study of the immune mechanism of IBV.

Objective To establish a pediatric rare disease catalog,analyze the current status of therapeutic drugs and their coverage of the medical insurance in China,and propose strategies to enhance drug accessibility.Methods Pediatric rare diseases were identified from China's two national rare disease catalogs combined with the EU Orphanet database,US FDA orphan drug database,and the Diagnosis and Treatment Standards for Rare Diseases in Children.We created a specialized drug catalog for pediatric rare diseases,then analyzed drug types(ATC classification),pricing,and medical insurance coverage using descriptive statistics based on Yaozhi.com drug bidding prices and the 2024 Drug of List National Basic Medical Insurance(NBMIDL).Drug affordability was assessed through annual treatment cost calculations.Results The national catalogs included 151 pediatric rare diseases(72.95%of listed conditions),spanning 13 disease systems.We identified 94 dedicated orphan drugs(by generic name)for these conditions,among which 43 were approved internationally but unavailable in China.The average unit price per package was 6 113.53 yuan.Overall NBMIDL coverage was 68.83%,but drugs priced above 7 000 yuan per unit had only 7.69%coverage.Annual treatment costs reached 4.54 million for laronidase(mucopolysaccharidosis).Conclusions Critical gaps persist in China's pediatric rare disease treatment landscape,including catalog deficiencies,inadequate coverage for high-cost drugs and insufficient domestic innovation.It is recommended to establish a list of orphan drugs for pediatric rare diseases,accelerate the import of foreign drugs and the local innovative drugs through policy incentives,optimizing medical insurance reimbursement mechanisms for pediatric rare disease drugs to comprehensively improve therapeutic accessibility.

Objective:To explore the risk factors of severe acute kidney injury (AKI) in septic patients, and to establish an hour-specific prediction model.Methods:Based on the information of septic patients in the Medical Information Mart for Intensive Care-Ⅳ (MIMIC-Ⅳ) database, general information, comorbidities, vital signs, severity scoring system, laboratory indicators, invasive operations and medication use were recorded. The enrolled patients were randomized into a training set and a validation set according to a ratio of 7∶3. AKI was diagnosed according to the guidelines of Kidney Disease: Improving Global Outcome (KDIGO). Based on Lasso regression and Cox regression, the risk factors of severe AKI (AKI stage 2 and stage 3) in septic patients were analyzed and hour-specific prediction model were established. Consistency index (C-index), area under the receiver operator characteristic curve (AUC) and calibration curve were used to assess the predictive efficacy of the model.Results:A total of 20 551 septic patients were enrolled, including 14 385 patients in the training set and 6 166 patients in the validation set. Multivariate Cox regression analysis showed that atrial fibrillation [hazard ratio ( HR) = 1.266, 95% confidence interval (95% CI) was 1.150-1.393], heart failure ( HR = 1.348, 95% CI was 1.217-1.493), respiratory failure ( HR = 1.565, 95% CI was 1.428-1.715), heart rate ( HR = 1.004, 95% CI was 1.002-1.007), mean arterial pressure ( HR = 1.245, 95% CI was 1.126-1.377), lactic acid ( HR = 1.051, 95% CI was 1.025-1.077), simplified acute physiology score Ⅱ (SAPSⅡ, HR = 1.019, 95% CI was 1.016-1.023), serum creatinine ( HR = 1.171, 95% CI was 1.127-1.216), anion gap ( HR = 1.024, 95% CI was 1.010-1.038), serum potassium ( HR = 1.155, 95% CI was 1.079-1.236), white blood cell count ( HR = 1.006, 95% CI was 1.003-1.009) and furosemide use ( HR = 0.414, 95% CI was 0.368-0.467) were independently associated with severe AKI in septic patients (all P < 0.01). The above predictors were applied to construct an hour-specific prediction model for the occurrence of severe AKI in septic patients. The C-index of the prediction model was 0.723 and 0.735 in the training and validation sets, respectively. The AUC for the occurrence of severe AKI at 12, 24, and 48 hours were 0.795 (95% CI was 0.782-0.808), 0.792 (95% CI was 0.780-0.805), and 0.775 (95% CI was 0.762-0.788) in the training set, and the AUC were 0.803 (95% CI was 0.784-0.823), 0.791 (95% CI was 0.772-0.810), and 0.773 (95% CI was 0.752-0.793) in the validation set, respectively. The calibration curves of the two cohorts were in good agreement. Conclusion:The hour-specific prediction model effectively identifies high-risk septic patients for developing severe AKI within 48 hours, aiding clinicians in stratifying patients for early therapeutic interventions to improve outcomes.

Objective: In order to master the epidemic trend of corona virus disease 2019 (COVID-19) and evaluate the effect of prevention and control, we evaluate the epidemic dynamics of COVID-19 in mainland China, Hubei province, Wuhan city and other provinces outside Hubei from January 16 to February 14, 2020. Methods: We collected the daily number of new confirmed COVID-19 cases by nucleic acid detection reported by the National Health Commission from January 16, 2020 to February 14, 2020. The analysis includes the epidemic curve of the new confirmed cases, multiple of the new confirmed cases for period-over-period, multiple of the new confirmed cases for fixed-base, and the period-over-period growth rate of the new confirmed cases. Results: From January 16 to February 14, 2020, the cumulative number of new confirmed cases of COVID-19 in mainland China was 50 031, including 37 930 in Hubei province, 22 883 in Wuhan city and 12 101 in other provinces outside Hubei. The peak of the number of new confirmed cases in other provinces outside Hubei was from January 31 to February 4, 2020, and the peak of new confirmed cases in Wuhan city and Hubei province was from February 5 to February 9, 2020. The number of new confirmed cases in other provinces outside Hubei showed a significant decline (23% compared with the peak) from February 5 to February 9, 2020, while the number of new confirmed cases in Wuhan city (30% compared with the peak) and Hubei Province (37% compared with the peak) decreased significantly from February 10 to February 14, 2020. Conclusion The epidemic prevention and control measures taken by the state and governments at all levels have shown very significant effects, effectively curbing the spread of the COVID-19 epidemic in China.

Objective:To study the effects of cisapride on digestive symptoms and gastrointestinal hormones in elderly peritoneal dialysis patients.Methods:Forty-two elderly patients with renal failure undergoing peritoneal dialysis in our hospital from July 2017 to December 2017 were randomly selected as the study group.Meanwhile, 20 healthy elderly people in the corresponding time period were selected as the control group.Control group received continuous ambulatory peritoneal dialysis(CAPD)and other conventional basic therapy, and study group received cisapride as add-on therapy to treatment for control group.Serum levels of somatostatin(SS), motilin(MOT)and vasoactive intestinal peptide(VIP)were compared between the two groups.Gastrointestinal symptoms, serum levels of gastrointestinal hormones and biochemical indexes were compared before and after treatment in the study group.Results:The score of acid reflux, nausea, abdominal distension, belching and constipation were lower in the study group after treatment than before treatment( t=4.42, 4.32, 6.80, 6.29 and 6.76, all P=0.00). Before treatment, levels of MOT, SS and VIP were higher in the study group than in the control group[(636.65±32.02)pmol/L vs.(228.47±28.74)pmol/L, (64.02±16.32)mg/L vs.(42.38±6.42)mg/L, (118.64±17.68)ng/L vs.(58.62±11.63)ng/L, t=48.44, 7.47 and 15.93, all P=0.00]. The level of MOT was lower after than before treatment[(385.36±19.64)pmol/L vs.(636.65±32.02)pmol/L, t=43.36, P=0.00], and the levels of SS and VIP had no significant difference before versus after treatment( t=-0.11 and -0.42, P=0.91 and 0.68). After treatment, the level of MOT was still higher in the study group than in the control group[(385.36 ±19.64)pmol/L vs.(228.47 ±28.74)pmol/L, t=22.08, P=0.00]. There was no significant difference in blood urea nitrogen(BUN), creatinine, haemoglobin and kt/v levels between before and after treatment( P>0.05). The level of albumin(ALB)was higher after than before treatment[(38.60±1.89)g/L vs.(37.71±1.96)g/L, t=2.12, P=0.04]. Conclusions:Gastrointestinal symptoms are common in elderly patients with peritoneal dialysis, and the accumulation of gastrointestinal hormones is obvious, which leads to gastrointestinal dysfunction.The conventional treatment in combination with cisapride can improve gastrointestinal symptoms and reduce serum MOT level in these patients.

Objective To investigate the effects and related risk factors of different vascular access types on new atrial fibrillation in maintenance hemodialysis (MHD) patients.Methods This was a single-center prospective cohort study.Patients who established long-term dialysis access and were voluntarily followed up in the Second Hospital of Tianjin Medical University from January 1,2013 to June 30,2013 were enrolled to follow-up for 5 years.Patients were divided into fistula group (patients with autogenous arteriovenous fistula) and catheter group (patients with tunneled cuffed internal jugular vein catheter).The incidences of new atrial fibrillation in the two groups were compared by Kaplan-Meier survival analysis.Cox regression analysis and receiver operator characteristic curve (ROC) were used to assess the risk factors of new atrial fibrillation.Results A total of 315 eligible patients were enrolled,including 150 males (47.62％).There were 189 patients (60.00％) in the fistula group,and 126 patients (40.00％) in the catheter group.Multivariate Cox regression analysis showed that older age (HR=1.021,95％CI 1.003-1.040),arteriovenous fistula (HR=1.899,95％CI 1.019-3.539),increased dialysis blood flow (HR=1.030,95％CI 1.010-1.051) and left atrial diameter (HR=1.097,95％CI 1.022-1.177) were independent risk factors for new atrial fibrillation in MHD patients (all P ＜ 0.05).Kaplan-Meier survival analysis showed that the incidence of new atrial fibrillation in fistula group was higher than that in catheter group (Log-rank A2=9.53,P=0.002).ROC curve analysis showed that age [the area under the curve (AUC)=0.608,P=0.008],arteriovenous fistula (AUC=0.594,P=0.021),dialysis blood flow (AUC=0.659,P＜0.001) and left atrial diameter (AUC=0.604,P=0.011) could predict the occurrence of new atrial fibrillation.Condusions Older age,arteriovenous fistula,increased blood flow during dialysis and left atrial diameter are independent risk factors for new atrial fibrillation in MHD patients,which can predict the occurrence of atrial fibrillation.The incidence of new atrial fibrillation in patients with arteriovenous fistula is higher than that in patients with catheter.

One hundred and twenty maintenance hemodialysis patients with secondary hyperparathyroidism were randomly assigned to receive cinacalce,calcitriol or combination of cinacalce and cacitriol for treatment,with 40 cases in each group.Patients were followed up for 12 months;and the blood tests,echocardiography,examinations for osteoporosis and soft tissue calcification were performed every month.After 3 months of treatment,the serum levels of parathyroid hormone were decreased in all three groups (P ＜ 0.01);while the parathyroid hormone decreased more markedly with less influence on serum calcium and phosphorus levels in combination group.There were no significant changes in alkaline phosphatase,osteoporosis and cardiac valve calcification after treatment,compared with before treatment.There were no cases of hypercalcemia and hypocalcemia appearing in combination group after treatment.The study indicates that the combination of cinacalcet with calcitriol has better therapeutic effect for treatment of secondary hyperparathyroidism in maintenance dialysis patients.