Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

In order to investigate the related pathogens and reveal the etiological characteristics of gout in goslings,191 typical clinical cases from partial regions of China were examined by RT-PCR/PCR detection of viral nucleic acids in domestic poultry and pathological analysis.The autop-sy results show that the clinical cases could be classified into three types based on the severity of urate deposition:severe,moderate,and mild,namely systemic urate deposition,local urate deposi-tion mainly in the liver and kidneys,and only a small amount of fine-grained urate deposition in the liver,gallbladder,or glandular stomach.The results of RT-PCR/PCR detection showed that the to-tal positive rates were as follows:GAstV Group2 63.9％,GAstV Group1 50.3％,AAstV-2 38.7％,novel Muscovy duck parvovirus(NPV)17.8％,GPV 16.2％,GoCV 12.6％,MDPV 7.9％,MDRV 8.4％,DPV 0.5％,GPMV and NDV 0.5％,the AstV-1、ARV、TMUV、NDV、FAdV、GHPyV were zero.Among all the postive samples,the rates of single positive,double positive,and multiple posi-tive were 18.3％,27.2％,and 44.0％,respectively.The rate of single positive samples containing AAstV was only 12.0％,the double or multiple positive samples containing GAstV Group 1/2 was 60.7％,and the rate of samples without GAstV Group 1/2 was 10.5％.The results also showed that 20(10.5％)samples were negative for 16 types of viruses.The AAstV particles isolated from single positive samples appear spherical shape,non-enveloped and 20-80 nm minsize.Two types of virus particles which with spherical shape and diameters of 40-100 and 20-40 nm can be isolated from the negative samples.The virus inoculation results show that the goose embryos can be led to death by clinical GAstV isolates,which with classic histopathological characteristics.Although the GAstV isolates cannot led to death and obvious typical histopathological change in goslings,the vi-ral nucleic acids can be detected in heart,liver,spleen,kidney,intestine and cloacal anal swabs.The above results indicated that there were multiple pathogens co-infection dominated by AAstv in Gosling gout in China,including cross species infections of multiple AAstVs,parvovirus,ARV and suspec-ted novel viruses.Moreover,the GAstV maybe not the only pathogen causing gout in goslings.

Objective:To study the optimal anastomotic angle of end-to-side anastomosis autogenous arteriovenous fistula (AVF).Methods:A case-report and case-series design was used to obtain clinical data on 10 patients with diabetic nephropathy from Department of Nephrology, the 905th Hospital of the Chinese People′s Liberation Army Navy from June 2024 to February 2025. The models of "radial artery-cephalic vein" end-to-side anastomosis in the forearm with anastomotic angles of 30°, 40°and 50°were established. Numerical simulation was used to analyze the blood flow in the model, and to study the effect of different anastomotic angles on blood flow. Wall shear stress (WSS), cross section flow velocity and flow rate, and relative residence time (RRT) were studied in the model. The Whitney test with Holm correction was used to evaluate the difference in the median RRT between the three angle models.Results:At the moment of 0.65 s, the area fraction of low wall shear stress (LWSS) in the 30° model was 7.7%, which was reduced by 2.4% and 3.7% compared to the 40°and 50°models, respectively. At the time of 0.2 s, the area proportions of high wall shear stress (HWSS) in the 30°, 40°and 50°models were 54.4%, 43.9% and 37.4%, respectively. At 0.2 s, the maximum cross section flow velocity reached 4.07, 3.84 and 3.67 m/s for the 30°, 40°and 50°models, respectively. In the cycle, the maximum mean flow velocity for the 30°model reached 1.20 m/s. The mean flow rates of the 30°, 40°and 50°models in the J-5 cross section were 349, 316, and 328 ml/min, respectivly. For patient 6, the area proportions of the RRT>1 region were 11.97%, 14.84% and 15.22% for the 30°, 40°and 50°models, respectively.Conclusions:The optimal anastomotic angle of "radial artery-cephalic vein" for end-to-side anastomosis AVF surgery in patients with diabetic nephropathy is 40°.

Objective:To develop a 5-year mortality risk prediction model for patients with small cell neuroendocrine carcinoma of the cervix(SCNEC).Methods:Based on the Surveillance,Epidemiology,and End Results(SEER)database and R software version 4.3.3,variables were screened via Lasso regression,followed by multivariable logistic regression and stepwise regression to develop a 5-year mortality risk prediction model for SCNEC patients.The Akaike Information Criterion(AIC),C-index,receiver operating characteristic(ROC)curve,Hosmer-Lemeshow test,and calibration curve were employed to evaluate the model.Results:Age,M stage,surgical status,and lymph node metastasis were ultimately selected as variables to construct the 5-year mortality risk prediction model for SCNEC patients.The model demonstrated superior predictive performance compared to FIGO staging(P＜0.01).The Hosmer-Lemeshow test yielded a P-value＞0.05.The C-index values for the training and validation sets were 0.808 and 0.755,respectively,with the areas under the ROC curves of 0.826 and 0.744.The calibration curves of the model fluctuated near the diagonal line,indicating good agreement between predicted and observed outcomes.The decision curve analysis demonstrated significant clinical net benefit.Results showed that higher mortality risk was associated with advanced age,M1 status,lymph node metastasis,and lack of surgical opportunity.Conclusions:The model exhibits good discriminatory power and accuracy,providing significant benefits to patients.Enhanced management should be implemented for patients with advanced age,distant metastasis,lymph node metastasis,or ineligibility for surgery.Lymph node metastasis is an independent risk factor for 5-year mortality in patients with SCNEC.

Goose astrovirus(GAstV)has become one of the most important pathogens endangering the goose farming industry in China.To discover the genomic information of prevalent strains in China in 2022 and reveal their biological characteristics,the whole genomes of 9 strains of GAstV-1 and 12 strains of GAstV-2 isolated from parts of China in 2022 were sequenced by the Chromo-some Walking and analyzed by bioinformatics software and websites.The analysis results of gene structure showed that the sizes of the coding genes ranged from 6 977 to 7 215 bp.The open read-ing frame 1(ORF1)of all strains contained the characteristic motifs of serine protease,nuclear lo-calization signal(NLS)and RNA-dependent RNA polymerase(RdRp).The ribosomal frameshift signals(RFS)were all in the form of stem-loop structures.However,the numbers of stem and loop nucleotides in GAstV-1 were"14+11"configuration,while those in GAstV-2 were"12+14"configuration,and the loop of GAstV-2 was in the"8+6"double-loop configuration.The results of homological analysis for ORF1b showed that the homology of the GAstV-1 isolats compared with the representative strains of avian astrovirus types 1,2,and 3(AAstV-1,AAstV-2,AAstV-3)ranged from 7％to 64％,and the homology of the GAstV-2 isolates ranged from 8％to 68％.The average genetic distances of ORF2 were 0.9,1.2,and 0.9 respectively compared with the represent-ative strains of AAstV-1,AAstV-2 and AAstV-3.While for the GAstV-2 isolates,the highest ho-mologies were 68％and 56％,the lowest homologies were 8％and 36％respectively.And the aver-age genetic distances of ORF2 were 1.0,1.2,and 0.5 respectively.B-cell-conformational epitopes screening results of ORF2 showed that,there were four common epitopes in the GAstV Group 1 i-solates,namely PRE,LALQSQSVNTFA,AAG and YQQVTSDQSI except for N-145,N-287 and N-314 in the two strains G1FJ267 and G1JS277.And there were seven common conformational epitopes in the GAstV-2 isolates,namely NQE,RAN,GPE,PRQ,TRAQ,SNS,and AVPPNTPL except for N-83,N-136,N-331 and N-351 in the strain G2FJ283-3B.The above results indicated that GAstV maybe belong to a new type of AAstV because of the difference between the clinical i-solates and the known strains of AAstV.And there was pathogenic diversity among the isolates.All the isolates of GAstV-1 and GAstV-2 belong to two different serotypes,and the possible serologi-cal subtypes among the isolates of GAstV-1 or GAstV-2 are remained to be further identified by serological tests.

Objective:To investigate the status quo of cognitive frailty in elderly patients with heart failure and analyze its influencing factors, so as to provide evidence for healthcare professionals to formulate effective intervention strategies.Methods:A total of 330 elderly patients with heart failure admitted to the First Affiliated Hospital of the University of South China and the Second Affiliated Hospital of the University of South China from October 2023 to January 2024 were selected as the study objects by convenience sampling method. General data questionnaire, Frailty Phenotype, Montreal Cognitive Assessment, Clinical Dementia Rating Scale, Geriatric Depression Scale-15 and Short Form Mini Nutritional Assessment were used for a sectional investigation. Random forest algorithm was used to rank the importance of variables and binary logistic regression was combined to explore the influencing factors of elderly patients with heart failure.Results:According to the evaluation criteria of cognitive frailty, 330 elderly patients with heart failure were divided into cognitive frailty group (124 cases) and non-cognitive frailty group (206 cases). The incidence of cognitive frailty was 37.6% (124/330). Among which, the median age of the cognitive frailty group was 73 years old, with 63 males and 61 females. The median age of the non-cognitive frailty group was 71 years old, with 117 males and 89 females. The random forest results showed that the top 7 variables in importance ranking were weekly intellectual activity, frequency of physical exercise, age, educational levels, depression status, cardiac function grade and risk of malnutrition. Binary logistic regression analysis showed that weekly intellectual activity ( OR=0.076, 95% CI 0.027-0.216), requency of physical exercise ( OR=0.184, 95% CI 0.079-0.430), age ( OR=1.173, 95% CI 1.077-1.277), educational levels ( OR=0.283, 95% CI 0.143-0.559), depression status ( OR=4.440, 95% CI 1.451-13.585), cardiac function grade ( OR=3.030, 95% CI 1.673-5.489) and risk of malnutrition ( OR=3.833, 95% CI 1.530-9.602) were the main influencing factors (all P<0.05). Conclusions:The incidence of cognitive frailty in elderly patients with heart failure is high. Healthcare professionals ought to focus on the screening and assessing of cognitive frailty in elderly patients with heart failure, and formulate effective intervention strategies by considering the above influencing factors to mitigate the occurrence of cognitive frailty.

In order to investigate the related pathogens and reveal the etiological characteristics of gout in goslings,191 typical clinical cases from partial regions of China were examined by RT-PCR/PCR detection of viral nucleic acids in domestic poultry and pathological analysis.The autop-sy results show that the clinical cases could be classified into three types based on the severity of urate deposition:severe,moderate,and mild,namely systemic urate deposition,local urate deposi-tion mainly in the liver and kidneys,and only a small amount of fine-grained urate deposition in the liver,gallbladder,or glandular stomach.The results of RT-PCR/PCR detection showed that the to-tal positive rates were as follows:GAstV Group2 63.9％,GAstV Group1 50.3％,AAstV-2 38.7％,novel Muscovy duck parvovirus(NPV)17.8％,GPV 16.2％,GoCV 12.6％,MDPV 7.9％,MDRV 8.4％,DPV 0.5％,GPMV and NDV 0.5％,the AstV-1、ARV、TMUV、NDV、FAdV、GHPyV were zero.Among all the postive samples,the rates of single positive,double positive,and multiple posi-tive were 18.3％,27.2％,and 44.0％,respectively.The rate of single positive samples containing AAstV was only 12.0％,the double or multiple positive samples containing GAstV Group 1/2 was 60.7％,and the rate of samples without GAstV Group 1/2 was 10.5％.The results also showed that 20(10.5％)samples were negative for 16 types of viruses.The AAstV particles isolated from single positive samples appear spherical shape,non-enveloped and 20-80 nm minsize.Two types of virus particles which with spherical shape and diameters of 40-100 and 20-40 nm can be isolated from the negative samples.The virus inoculation results show that the goose embryos can be led to death by clinical GAstV isolates,which with classic histopathological characteristics.Although the GAstV isolates cannot led to death and obvious typical histopathological change in goslings,the vi-ral nucleic acids can be detected in heart,liver,spleen,kidney,intestine and cloacal anal swabs.The above results indicated that there were multiple pathogens co-infection dominated by AAstv in Gosling gout in China,including cross species infections of multiple AAstVs,parvovirus,ARV and suspec-ted novel viruses.Moreover,the GAstV maybe not the only pathogen causing gout in goslings.

Goose astrovirus(GAstV)has become one of the most important pathogens endangering the goose farming industry in China.To discover the genomic information of prevalent strains in China in 2022 and reveal their biological characteristics,the whole genomes of 9 strains of GAstV-1 and 12 strains of GAstV-2 isolated from parts of China in 2022 were sequenced by the Chromo-some Walking and analyzed by bioinformatics software and websites.The analysis results of gene structure showed that the sizes of the coding genes ranged from 6 977 to 7 215 bp.The open read-ing frame 1(ORF1)of all strains contained the characteristic motifs of serine protease,nuclear lo-calization signal(NLS)and RNA-dependent RNA polymerase(RdRp).The ribosomal frameshift signals(RFS)were all in the form of stem-loop structures.However,the numbers of stem and loop nucleotides in GAstV-1 were"14+11"configuration,while those in GAstV-2 were"12+14"configuration,and the loop of GAstV-2 was in the"8+6"double-loop configuration.The results of homological analysis for ORF1b showed that the homology of the GAstV-1 isolats compared with the representative strains of avian astrovirus types 1,2,and 3(AAstV-1,AAstV-2,AAstV-3)ranged from 7％to 64％,and the homology of the GAstV-2 isolates ranged from 8％to 68％.The average genetic distances of ORF2 were 0.9,1.2,and 0.9 respectively compared with the represent-ative strains of AAstV-1,AAstV-2 and AAstV-3.While for the GAstV-2 isolates,the highest ho-mologies were 68％and 56％,the lowest homologies were 8％and 36％respectively.And the aver-age genetic distances of ORF2 were 1.0,1.2,and 0.5 respectively.B-cell-conformational epitopes screening results of ORF2 showed that,there were four common epitopes in the GAstV Group 1 i-solates,namely PRE,LALQSQSVNTFA,AAG and YQQVTSDQSI except for N-145,N-287 and N-314 in the two strains G1FJ267 and G1JS277.And there were seven common conformational epitopes in the GAstV-2 isolates,namely NQE,RAN,GPE,PRQ,TRAQ,SNS,and AVPPNTPL except for N-83,N-136,N-331 and N-351 in the strain G2FJ283-3B.The above results indicated that GAstV maybe belong to a new type of AAstV because of the difference between the clinical i-solates and the known strains of AAstV.And there was pathogenic diversity among the isolates.All the isolates of GAstV-1 and GAstV-2 belong to two different serotypes,and the possible serologi-cal subtypes among the isolates of GAstV-1 or GAstV-2 are remained to be further identified by serological tests.

Objective:To develop a 5-year mortality risk prediction model for patients with small cell neuroendocrine carcinoma of the cervix(SCNEC).Methods:Based on the Surveillance,Epidemiology,and End Results(SEER)database and R software version 4.3.3,variables were screened via Lasso regression,followed by multivariable logistic regression and stepwise regression to develop a 5-year mortality risk prediction model for SCNEC patients.The Akaike Information Criterion(AIC),C-index,receiver operating characteristic(ROC)curve,Hosmer-Lemeshow test,and calibration curve were employed to evaluate the model.Results:Age,M stage,surgical status,and lymph node metastasis were ultimately selected as variables to construct the 5-year mortality risk prediction model for SCNEC patients.The model demonstrated superior predictive performance compared to FIGO staging(P＜0.01).The Hosmer-Lemeshow test yielded a P-value＞0.05.The C-index values for the training and validation sets were 0.808 and 0.755,respectively,with the areas under the ROC curves of 0.826 and 0.744.The calibration curves of the model fluctuated near the diagonal line,indicating good agreement between predicted and observed outcomes.The decision curve analysis demonstrated significant clinical net benefit.Results showed that higher mortality risk was associated with advanced age,M1 status,lymph node metastasis,and lack of surgical opportunity.Conclusions:The model exhibits good discriminatory power and accuracy,providing significant benefits to patients.Enhanced management should be implemented for patients with advanced age,distant metastasis,lymph node metastasis,or ineligibility for surgery.Lymph node metastasis is an independent risk factor for 5-year mortality in patients with SCNEC.