Objective:To expand the mutation spectrum of familial benign chronic pemphigus (HHD), and to deeply explore the relationship between clinical phenotypes and genotypes.Methods:HHD patients were retrospectively collected from the Department of Dermatology, Hospital for Skin Diseases, Shandong First Medical University from January 2018 to October 2023, and their clinical data and blood samples were also collected. Sanger sequencing and Whole-exome sequencing were performed on 34 HHD patients. Mutations in the ATP2C1 gene were classified into loss-of-function mutations (including frameshift mutations, nonsense mutations, and splicing mutations) and missense mutations. The relationship between clinical phenotypes and genetic mutation types was analyzed using Fisher's exact test or two-independent-sample t test, and further verified by meta-analysis. Results:The 34 HHD patients were all of Chinese Han nationality, including 20 males and 14 females, and their ages ranged from 35 to 77 years. Pathogenic mutations in the ATP2C1 gene were successfully identified in all the 34 patients, including 29 independent mutations, among which there were 9 frameshift mutations, 8 splicing mutations, 6 missense mutations, and 6 nonsense mutations. The age at onset was significantly earlier in the loss-of-function mutation group (37.62 ± 10.10 years) than in the missense mutation group (49.63 ± 14.90 years; t = 2.62, P = 0.013). However, there were no significant differences in gender, family history, disease seasonality, disease severity, or disease progression among patients with different mutation types (all P > 0.05). Meta-analysis showed that the age at onset was significantly earlier in Chinese Han patients with HHD carrying loss-of-function mutations than in those carrying missense mutations (mean difference: -4.61 years, 95% CI: -8.68 - -0.53 years, P = 0.030) . Conclusion:Chinese Han patients with HHD carrying loss-of-function mutations in the ATP2C1 gene showed significantly earlier ages at onset compared with those carrying missense mutations.

Objective:To screen the optimal machine learning model for predicting the recurrence condition of hepatocellular carcinoma (HCC) at different time points post-surgery, based on the cutoff value of the Ki67 positive proliferation index condition calculated from recurrence-free survival and combined with various clinical features.Methods:retrospective study included initially treated patients with solitary HCC who underwent radical surgery at the Fifth Medical Center of the PLA General Hospital from January 2013 to March 2023. Data included general clinical data, preoperative laboratory parameters, and surgical pathology information about the subjects. The postoperative recurrence status was assessed by querying the medical record system or by telephone follow-up. The Ki67 positive index cutoff value was determined by the X-tile software based on the patient's recurrence-free survival status and time analysis. Survival rates were calculated using the Kaplan-Meier method, and survival curves were plotted. The study population was randomly divided into training and testing groups in a 7:3 ratio using a computer-generated random number method. The minimum redundancy maximum relevance (mRMR) method was used for feature variable selection. Predictive models for postoperative HCC recurrence conditions in patients with HCC were constructed using random forest, support vector machine, logistic regression, and gradient boosting decision tree machine learning algorithms. Inter-group comparisons for continuous data were performed using the t-test or Mann-Whitney U test. Inter-group comparisons of enumeration data were performed using the Pearson χ2 test, continuity-corrected χ2 test, or Fisher's exact test. Results:The cutoff values for the Ki67 positivity index were 0.3 and 0.5 in 510 cases, with a follow-up time ranging from 1.2 to 11.4 years (median: 6.2 years). The recurrence-free survival time was between 1 and 135 months (median: 32 months), with recurrence-free survival rates post-surgery at 1, 2, 3, and 5 years were 87.5%, 77.1%, 61.2%, and 54.5%, respectively. The top five variables predicted HCC recurrence and non-recurrence conditions following surgical follow-up at 6 months, 1 year, 2 years, and beyond 2 years, in accordance with information obtained by the mRMR screen out. The Ki67 positivity index screened a successfully constructed machine learning model to predict HCC recurrence and non-recurrence conditions following surgical follow-up at 6 months, 1 year, 2 years, and beyond 2 years. The machine learning model based on the gradient boosting decision tree algorithm had the best prediction performance among them (areas under the receiver operating characteristic curves for predicting HCC recurrence within six months in the training and validation sets were 0.996 and 0.946, and accuracies were 0.972 and 0.935, respectively).Conclusion:A machine learning model was successfully constructed using the Ki67 positivity index combined with four readily available clinical features to predict HCC recurrence. The machine learning model based on the gradient boosting decision tree algorithm demonstrated the best performance in terms of predicting HCC recurrence within six months after surgery.

Objectives:To analyze the clinical application effect of the preloaded snare technique in patients with risk of atrial septal occluder migration during percutaneous atrial septal defect(ASD)occlusion.Methods:The clinical data of 24 patients with secundum ASD who underwent preloaded snare-assisted transcatheter closure in Fuwai Central China Cardiovascular Hospital between December 2022 and August 2024 were retrospectively analyzed.The preprocedural echocardiography revealed that all patients presented with large secundum ASD or insufficient margins,indicating potential risk of device migration during percutaneous ASD occlusion.Consequently,preloaded snare technique was applied for ASD closure.Postprocedural evaluations were conducted to assess device stability(migration or shedding),residual shunt,pericardial effusion,and new-onset arrhythmia during the procedure,immediately after intervention,and at 1-month follow-up.Results:Among 24 patients,there were 4 males,with an average age of(37.88±13.18)years and an average weight of(59.70±10.78)kg.Twenty-two cases underwent successful interventional closure.Two cases occurred atrial septal occluder migration during the procedure,both were successfully retrieved using the preloaded snare and subsequently scheduled for surgical repair.Postprocedural electrocardiograms and echocardiograms(obtained immediately and at 1-month follow-up)demonstrated no device migration,residual shunt,occluder dislodgement,pericardial effusion,or new-onset arrhythmias.Conclusions:The preloaded snare technique can reduce the risk of atrial septal occluder migration and shedding,simplify the process of retrieving the occluder,enhance the safety of the intervention,and avoid emergency surgical intervention in high-risk populations.

Diseases caused by animal virus infection seriously restricts the healthy development of animal husbandry.In-depth study of the molecular mechanism of viral replication and pathogenesis will provide theoretical basis for screening vaccine and drug targets.N6-methyladenosine(m6 A)modification occurs extensively in viral and host transcriptomes and affects viral replication and pathogenicity by regulating gene expression,which acts as a novel regulator of gene expression in addition to DNA and protein modifications.Insight into the regulatory molecular mechanism of m6 A modification in virus infection is the research hotspots and frontiers.In recent years,there are re-ports of alternation of the m6 A modification-associated epitranscriptomes and related function a-nalysis during virus infection.Here,we summarize the alternation of the epitranscriptomes induced by African swine fever virus(ASFV),porcine reproductive and respiratory syndrome virus(PRRSV),porcine epidemic diarrhoea virus(PEDV),cestode virus(CSFV),porcine pseudorabies virus(PRV),Marek's disease virus(MDV),Newcastle disease virus(NDV),avian leukaemia virus(ALV)and duck hepatitis A virus(DHAV)infection,and the subsequent effects on viral replica-tion and pathogenicity.We also discuss the potential role and molecular mechanism of m6 A modification in animal virus replication and pathogenesis,which will contributes to the prevention and control for animal disease.

Objectives:To evaluate the feasibility and clinical efficacy of eccentric occluder for the treatment of ventricular septal defect(VSD)without distance from the aortic valve.Methods:This analysis included 16 patients(9 males and 7 females)with VSD without distance from the aortic valve,who were treated at Fuwai Central China Cardiovascular Hospital from February 2022 to June 2024.Ten cases had mild right coronary sinus prolapse,and 2 had mild aortic valve regurgitation.All patients were diagnosed with VSD located zero-distance from aortic valve through transthoracic echocardiography(TTE)and left ventricular angiography.Eccentric occluder was used for interventional closure.TTE and 12-lead electrocardiography(ECG)were performed at 1 month,3 months,and 6 months after surgery to observe the presence of residual shunt,aortic valve regurgitation,and cardiac electrical conduction abnormalities.Results:Transcatheter closure was successful in 15 patients,procedure failed in one patient due to the unstable fixation of the occluder.Average diameter of the defect is(4.37±1.53)mm,and the diameter of the occluder is 6.5(6.0,8.0)mm.Postoperative left ventricular angiography showed minimal residual shunt in 3 cases,and no complications such as pericardial tamponade,hemolysis,thromboembolism,or infection,were observed.At one month after occlusion,TTE results showed that residual shunt disappeared in 3 patients with residual shunt.During 3-month and 6-month follow-up,all the occluders were well-positioned with no new aortic valve regurgitation or worsening of the original regurgitation,and no atrioventricular block or bundle branch block and other electrocardiographic conduction abnormalities.Conclusions:The use of eccentric occluder for intervention of ventricular septal defect patients without distance from the aortic valve is safe and effective.

Objective:To expand the mutation spectrum of familial benign chronic pemphigus (HHD), and to deeply explore the relationship between clinical phenotypes and genotypes.Methods:HHD patients were retrospectively collected from the Department of Dermatology, Hospital for Skin Diseases, Shandong First Medical University from January 2018 to October 2023, and their clinical data and blood samples were also collected. Sanger sequencing and Whole-exome sequencing were performed on 34 HHD patients. Mutations in the ATP2C1 gene were classified into loss-of-function mutations (including frameshift mutations, nonsense mutations, and splicing mutations) and missense mutations. The relationship between clinical phenotypes and genetic mutation types was analyzed using Fisher's exact test or two-independent-sample t test, and further verified by meta-analysis. Results:The 34 HHD patients were all of Chinese Han nationality, including 20 males and 14 females, and their ages ranged from 35 to 77 years. Pathogenic mutations in the ATP2C1 gene were successfully identified in all the 34 patients, including 29 independent mutations, among which there were 9 frameshift mutations, 8 splicing mutations, 6 missense mutations, and 6 nonsense mutations. The age at onset was significantly earlier in the loss-of-function mutation group (37.62 ± 10.10 years) than in the missense mutation group (49.63 ± 14.90 years; t = 2.62, P = 0.013). However, there were no significant differences in gender, family history, disease seasonality, disease severity, or disease progression among patients with different mutation types (all P > 0.05). Meta-analysis showed that the age at onset was significantly earlier in Chinese Han patients with HHD carrying loss-of-function mutations than in those carrying missense mutations (mean difference: -4.61 years, 95% CI: -8.68 - -0.53 years, P = 0.030) . Conclusion:Chinese Han patients with HHD carrying loss-of-function mutations in the ATP2C1 gene showed significantly earlier ages at onset compared with those carrying missense mutations.

Objectives:To analyze the clinical application effect of the preloaded snare technique in patients with risk of atrial septal occluder migration during percutaneous atrial septal defect(ASD)occlusion.Methods:The clinical data of 24 patients with secundum ASD who underwent preloaded snare-assisted transcatheter closure in Fuwai Central China Cardiovascular Hospital between December 2022 and August 2024 were retrospectively analyzed.The preprocedural echocardiography revealed that all patients presented with large secundum ASD or insufficient margins,indicating potential risk of device migration during percutaneous ASD occlusion.Consequently,preloaded snare technique was applied for ASD closure.Postprocedural evaluations were conducted to assess device stability(migration or shedding),residual shunt,pericardial effusion,and new-onset arrhythmia during the procedure,immediately after intervention,and at 1-month follow-up.Results:Among 24 patients,there were 4 males,with an average age of(37.88±13.18)years and an average weight of(59.70±10.78)kg.Twenty-two cases underwent successful interventional closure.Two cases occurred atrial septal occluder migration during the procedure,both were successfully retrieved using the preloaded snare and subsequently scheduled for surgical repair.Postprocedural electrocardiograms and echocardiograms(obtained immediately and at 1-month follow-up)demonstrated no device migration,residual shunt,occluder dislodgement,pericardial effusion,or new-onset arrhythmias.Conclusions:The preloaded snare technique can reduce the risk of atrial septal occluder migration and shedding,simplify the process of retrieving the occluder,enhance the safety of the intervention,and avoid emergency surgical intervention in high-risk populations.

Nucleic acid aptamers are a type of single-stranded oligonucleotides screened through in vitro exponentially enriched ligand phylogenetic technology, and they can bind to various targets with high specificity and high affinity. AS1411 is a 26-base guanine-rich DNA aptamer, and its target nucleolin is widely distributed in multiple locations within the cell, including the nucleolus, nucleoplasm, cytoplasm and cell membrane. AS1411 demonstrates multiple advantages, such as weak immunogenicity, low toxicity, easy structural modification, and strong tissue penetration ability. Despite numerous challenges in the clinical transformation process, with the continuous advancement of molecular imaging technology, AS1411 has demonstrated great potential in the fields of targeted imaging and targeted delivery of cancer drugs. This article mainly focuses on the research progress of AS1411 in the field of molecular imaging, covering its applications in magnetic resonance imaging, fluorescence imaging and nuclear medicine imaging, etc.

Diseases caused by animal virus infection seriously restricts the healthy development of animal husbandry.In-depth study of the molecular mechanism of viral replication and pathogenesis will provide theoretical basis for screening vaccine and drug targets.N6-methyladenosine(m6 A)modification occurs extensively in viral and host transcriptomes and affects viral replication and pathogenicity by regulating gene expression,which acts as a novel regulator of gene expression in addition to DNA and protein modifications.Insight into the regulatory molecular mechanism of m6 A modification in virus infection is the research hotspots and frontiers.In recent years,there are re-ports of alternation of the m6 A modification-associated epitranscriptomes and related function a-nalysis during virus infection.Here,we summarize the alternation of the epitranscriptomes induced by African swine fever virus(ASFV),porcine reproductive and respiratory syndrome virus(PRRSV),porcine epidemic diarrhoea virus(PEDV),cestode virus(CSFV),porcine pseudorabies virus(PRV),Marek's disease virus(MDV),Newcastle disease virus(NDV),avian leukaemia virus(ALV)and duck hepatitis A virus(DHAV)infection,and the subsequent effects on viral replica-tion and pathogenicity.We also discuss the potential role and molecular mechanism of m6 A modification in animal virus replication and pathogenesis,which will contributes to the prevention and control for animal disease.

Objectives:To evaluate the feasibility and clinical efficacy of eccentric occluder for the treatment of ventricular septal defect(VSD)without distance from the aortic valve.Methods:This analysis included 16 patients(9 males and 7 females)with VSD without distance from the aortic valve,who were treated at Fuwai Central China Cardiovascular Hospital from February 2022 to June 2024.Ten cases had mild right coronary sinus prolapse,and 2 had mild aortic valve regurgitation.All patients were diagnosed with VSD located zero-distance from aortic valve through transthoracic echocardiography(TTE)and left ventricular angiography.Eccentric occluder was used for interventional closure.TTE and 12-lead electrocardiography(ECG)were performed at 1 month,3 months,and 6 months after surgery to observe the presence of residual shunt,aortic valve regurgitation,and cardiac electrical conduction abnormalities.Results:Transcatheter closure was successful in 15 patients,procedure failed in one patient due to the unstable fixation of the occluder.Average diameter of the defect is(4.37±1.53)mm,and the diameter of the occluder is 6.5(6.0,8.0)mm.Postoperative left ventricular angiography showed minimal residual shunt in 3 cases,and no complications such as pericardial tamponade,hemolysis,thromboembolism,or infection,were observed.At one month after occlusion,TTE results showed that residual shunt disappeared in 3 patients with residual shunt.During 3-month and 6-month follow-up,all the occluders were well-positioned with no new aortic valve regurgitation or worsening of the original regurgitation,and no atrioventricular block or bundle branch block and other electrocardiographic conduction abnormalities.Conclusions:The use of eccentric occluder for intervention of ventricular septal defect patients without distance from the aortic valve is safe and effective.