Objective To investigate the regulatory mechanism of transforming growth factor-β1 (TGF-β1) in different types of mitral valvular disease (MVD) with atrial fibrillation (AF). Methods From August 2011 to August 2012, patients with moderate to severe MVD accompanied by AF who required mitral valve replacement at the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, were included. Based on echocardiographic results, patients were divided into two groups: a mitral regurgitation (MR) with AF (MR-AF) group and a mitral stenosis (MS) with AF (MS-AF) group. Left atrial tissue samples were collected during surgery. Techniques such as enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, immunohistochemistry, and Western blotting were used to detect key molecules in the TGF-β1/JNK pathway. Results Sixteen patients were enrolled. There were 8 patients in the MR-AF group, including 5 males and 3 females, with an average age of (41.38±11.19) years; and 8 patients in the MS-AF group, including 6 males and 2 females, with an average age of (43.12±5.30) years. The left atrial volume load was higher in MR-AF patients, while the left atrial pressure load was higher in MS-AF patients. In MS-AF patients, the relative expression levels of MAPK9, JUN, CASP3, BAX, and BCL2 mRNA in left atrial tissues were significantly upregulated. The serum TGF-β1 protein level and the relative expression levels of p-JNK, p-c-Jun, and Caspase-3 proteins in the left atrial tissues of the MR-AF group were higher. Myocardial cell damage was more severe in the MS-AF group, and the protein expression level of Bcl-2 was higher. Conclusion Different MVD have distinct hemodynamic characteristics. The myocardium of the left atrium in MR-AF patients is more prone to apoptosis, possibly through the activation of the TGF-β1/JNK signaling pathway.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

The PA-PB1 interface of the influenza polymerase is an attractive site for antiviral drug design. In this study, we designed and synthesized a mini-library of indazole-containing compounds based on rational structure-based design to target the PB1-binding interface on PA. Biological evaluation of these compounds through a viral yield reduction assay revealed that compounds 27 and 31 both had a low micromolar range of the half maximal effective concentration (EC₅₀) values against A/WSN/33 (H1N1) (8.03 μmol/L for 27; 14.6 μmol/L for 31), while the most potent candidate 24 had an EC₅₀ value of 690 nM. Compound 24 was effective against different influenza strains including a pandemic H1N1 strain and an influenza B strain. Mechanistic studies confirmed that compound 24 bound PA with a K _d which equals to 1.88 μmol/L and disrupted the binding of PB1 to PA. The compound also decreased the lung viral titre in mice. In summary, we have identified a potent anti-influenza candidate with potency comparable to existing drugs and is effective against different viral strains. The therapeutic options for influenza infection have been limited by the occurrence of antiviral resistance, owing to the high mutation rate of viral proteins targeted by available drugs. To alleviate the public health burden of this issue, novel anti-influenza drugs are desired. In this study, we present our discovery of a novel class of indazole-containing compounds which exhibited favourable potency against both influenza A and B viruses. The EC₅₀ of the most potent compounds were within low micromolar to nanomolar concentrations. Furthermore, we show that the mouse lung viral titre decreased due to treatment with compound 24. Thus our findings identify promising candidates for further development of anti-influenza drugs suitable for clinical use.

Objective To retrospectively assess the clinical efficacy of acupuncture at the Huiyin point combined with Qingdu wash solution in the treatment of high-risk HPV infection.Methods A total of 264 patients who were initially diagnosed with high-risk HPV infection at the University City Gynecology Department of Guang-dong Provincial Hospital of Traditional Chinese Medicine between January 2022 and June 2024 were enrolled in the study.These patients were divided into two groups based on predefined inclusion and exclusion criteria.The ob-servation group included 134 patients who received acupuncture at the Huiyin acupoint combined with Qingdu wash solution,while the control group consisted of 130 patients who did not receive any intervention.The treatment pe-riod lasted for three months,during which the short-term clinical efficacy and safety profile were evaluated.Results The HR-HPV clearance rates in the observation group at 3 months and 6 months were 61.9%and 65.7%,respectively,which were significantly higher than those in the control group(16.9%and 21.5%),and the differences between the two groups were statistically significant(P<0.001).Following a three-month treatment regimen,the rate of HR-HPV positive-to-negative conversion in the observation group was significantly higher than that in the control group,with a statistically significant intergroup difference(P<0.001).The improvement in tra-ditional Chinese medicine(TCM)-related symptoms was also significantly better in the observation group compared to the control group(P<0.05).During the follow-up period,no cases of recurrence were observed in the observa-tion group,whereas the recurrence rate in the control group was 1.5%.Furthermore,no adverse reactions were re-ported in the observation group throughout the treatment period.Conclusion Acupuncture at the Huiyin point,when combined with Qingdu wash solution,can enhance the therapeutic outcomes of high-risk HPV infection and demonstrates a favorable safety profile.

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

The integration of science and education is not only an important strategy for promoting social progress and technological development,but also a modern form of higher education aiming at cultivating innovative talents.Conducting scientific research training for undergraduate medical students is one of the important ways to cultivate their innovative abilities and comprehensive qualities.Our team proposed a"teaching,science,and ideology trinity"teaching model to comprehensively cultivate students' scientific research comprehensive abilities under the value orientation of ideological and political education by or-ganically integrating molecular biology experimental teaching with the scientific research training of under-graduate medical students.In this teaching activity,taking the experiment of gene polymorphism as an example,our team selected students with research potential from the whole grade and divided them into 4 project groups that were instructed by 4 teachers.The students were trained in the whole process of scien-tific research,including topic selection,project writing,experimental designing,application for research ethics,and project summary.Our team has always adhered to student-contentedness of educational con-cepts to stimulate students' intrinsic motivation throughout the teaching process.Students are the design-ers and implementers of the project,and teachers are only guides and promoters of learning.After this training,students not only became familiar with the writing and implementation of scientific research pro-jects,but also improved their literature reading,experimental designing,experimental skills,and prob-lem-solving abilities.More importantly,this teaching activity also cultivated students' awareness of re-search ethics and academic moral standards.

This study investigated the full-genome molecular characteristics of a rotavirus vaccine-derived strain,G1P[8]geno-type A group rotavirus RVA/Human-wt/CHN/HN1140/2021/G1P[8](referred to as HN1140).The gene fragments of the HN1140 strain were amplified with reverse transcription-polymerase chain reaction(RT-PCR)combined with whole-genome primers to obtain the full genome sequence.Genotyping was performed with the online genotyping tool RotaC 2.0,and similarity and genetic evolution analyses for each gene segment were conducted in DNAstar5.1 and MEGA11.0 software.The genotype of the HN1140 strain was deter-mined to be G1-P[8]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis demonstrated that all 11 genomic segments clus-tered closely with the RotaTeq vaccine strains,sharing 99.7%-100%nucleotide sequence similarity.Notably,VP1,VP2,VP6,and NSP2-NSP5 segments showed 100%nucleotide identity with RotaTeq strains.Comparative genomic analysis identified 13 nucleotide and 8 amino acid substitutions between HN1140 and RotaTeq strains,localized within the VP7,VP4,VP1,VP2,VP3,and NSP1 segments.The HN1140 strain exhibited the genotype G1-P[8]-A3-T6-H3,which was consistent with the typical profile of a vaccine-derived reassortant.This strain demonstrated high genetic similarity to RotaTeq vaccine strains,with nucleotide sequence identity ranging from 99.7%to 100%.These findings suggested that HN1140 evolved from RotaTeq vaccine strains through genetic reassortment.

The integration of science and education is not only an important strategy for promoting social progress and technological development,but also a modern form of higher education aiming at cultivating innovative talents.Conducting scientific research training for undergraduate medical students is one of the important ways to cultivate their innovative abilities and comprehensive qualities.Our team proposed a"teaching,science,and ideology trinity"teaching model to comprehensively cultivate students' scientific research comprehensive abilities under the value orientation of ideological and political education by or-ganically integrating molecular biology experimental teaching with the scientific research training of under-graduate medical students.In this teaching activity,taking the experiment of gene polymorphism as an example,our team selected students with research potential from the whole grade and divided them into 4 project groups that were instructed by 4 teachers.The students were trained in the whole process of scien-tific research,including topic selection,project writing,experimental designing,application for research ethics,and project summary.Our team has always adhered to student-contentedness of educational con-cepts to stimulate students' intrinsic motivation throughout the teaching process.Students are the design-ers and implementers of the project,and teachers are only guides and promoters of learning.After this training,students not only became familiar with the writing and implementation of scientific research pro-jects,but also improved their literature reading,experimental designing,experimental skills,and prob-lem-solving abilities.More importantly,this teaching activity also cultivated students' awareness of re-search ethics and academic moral standards.

This study investigated the full-genome molecular characteristics of a rotavirus vaccine-derived strain,G1P[8]geno-type A group rotavirus RVA/Human-wt/CHN/HN1140/2021/G1P[8](referred to as HN1140).The gene fragments of the HN1140 strain were amplified with reverse transcription-polymerase chain reaction(RT-PCR)combined with whole-genome primers to obtain the full genome sequence.Genotyping was performed with the online genotyping tool RotaC 2.0,and similarity and genetic evolution analyses for each gene segment were conducted in DNAstar5.1 and MEGA11.0 software.The genotype of the HN1140 strain was deter-mined to be G1-P[8]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis demonstrated that all 11 genomic segments clus-tered closely with the RotaTeq vaccine strains,sharing 99.7%-100%nucleotide sequence similarity.Notably,VP1,VP2,VP6,and NSP2-NSP5 segments showed 100%nucleotide identity with RotaTeq strains.Comparative genomic analysis identified 13 nucleotide and 8 amino acid substitutions between HN1140 and RotaTeq strains,localized within the VP7,VP4,VP1,VP2,VP3,and NSP1 segments.The HN1140 strain exhibited the genotype G1-P[8]-A3-T6-H3,which was consistent with the typical profile of a vaccine-derived reassortant.This strain demonstrated high genetic similarity to RotaTeq vaccine strains,with nucleotide sequence identity ranging from 99.7%to 100%.These findings suggested that HN1140 evolved from RotaTeq vaccine strains through genetic reassortment.