Respiratory viral infections pose serious threats to human health,particularly highlighted by recent pandemics caused by influenza viruses and coronaviruses.Natural products,characterized by their structural diversity and unique biological activities,offer promising resources for antiviral drug development.This review systematically summarizes the biological features,infection mechanisms,and antiviral targets of five major respiratory viruses—namely influenza virus,coronavirus,respiratory syncytial virus,human rhinovirus,and human metapneumovirus.It highlights recent progress in the discovery of antiviral natural products,including their chemical structures,mechanisms of action,and in vitro/in vivo activities.Many of these compounds not only inhibit viral entry and replication but also modulate host immune responses,exhibiting broad-spectrum,low-toxicity,and high-efficiency potential.This work aims to provide theoretical references and lead compound resources for future antiviral drug discovery and mechanistic re-search.

Respiratory viral infections pose serious threats to human health,particularly highlighted by recent pandemics caused by influenza viruses and coronaviruses.Natural products,characterized by their structural diversity and unique biological activities,offer promising resources for antiviral drug development.This review systematically summarizes the biological features,infection mechanisms,and antiviral targets of five major respiratory viruses—namely influenza virus,coronavirus,respiratory syncytial virus,human rhinovirus,and human metapneumovirus.It highlights recent progress in the discovery of antiviral natural products,including their chemical structures,mechanisms of action,and in vitro/in vivo activities.Many of these compounds not only inhibit viral entry and replication but also modulate host immune responses,exhibiting broad-spectrum,low-toxicity,and high-efficiency potential.This work aims to provide theoretical references and lead compound resources for future antiviral drug discovery and mechanistic re-search.

Objective:To explore the gene microarray of patients with ankylosing spondylitis in GEO database by using various bioinformatics methods, and to explore the possible targets and mechanisms of action.Methods:The GEO database was searched with "ankylosing spondylitis" the keyword, and the expression profile of genes related to AS was selected as the research object. Standard difference analysis, weighted co-expression analysis and gene set enrichment analysis were conducted to construct the disease set. GO and KEGG enrichment analysis were performed on the disease sets. The NCC algorithm identifies the first five key genes. THP-1 cells were implanted into RPMI-1640 culture medium containing 10% fetal bovine serum to multiply and construct the cell model of AS in vitro. The expression levels of 5 key genes were detected by qRT-PCR and Western blot. The experimental measurement data were expressed as mean± standard deviation, and the t test was used in comparison between the two groups. Results:One thousand six hundred and sixty seven disease genes were analyzed, functional annotation was mainly concentrated in 689 molecular components of cytoplasmic ribosomes, ribosomal subunits, ribosomes, cytoplasmic large ribosomal subunits, the structural composition of ribosomal REDOX enzyme activity, 1 002 molecular functions of NADH dehydrogenase activity, NADH dehydrogenase activity, and 5 764 molecular processes of mRNA catabolism and RNA catabolism The physical process involved 1 002 signaling pathways involved in Alzheimer′s disease, Prion disease, Parkinson′s disease, and the first 5 key genes were identified as RPS11, RPL4, RPL37A, RPS23, and RPS9. The experimental results were obtained by t test. The results showed that TNF-α mRNA ( t=5.59, P=0.001) and protein ( t=20.14, P<0.001) were significantly increased, indicating that LPS had induced inflammatory response in THP-1 cells, while RPL37AmRNA ( t=5.87, P=0.001), RPS11 mRNA ( t=3.88, P=0.008), RPS23 mRNA ( t=2.64, P=0.038), RPL37A protein ( t=3.18, P=0.030), RPS11 protein ( t=11.26, P<0.001), RPS23 protein ( t=5.64, P<0.001), increased, while RPS9 mRNA ( t=3.16, P=0.020), RPL4 mRNA ( t=2.54, P=0.044), RPS9 protein ( t=5.85, P<0.001) and RPL4 ( t=2.93, P=0.040) protein expressions decreased. RPL23 stimulated the joint synovial tissue to produce effect-T lymphocytes and release a large number of IL-2 and other inflammatory cytokines. RPS9 acts on the early stages of ribosomogenesis, and knocking down RPS9 reduced overall protein synthesis. RPL4 interacted with TTC22 protein to enhance the binding of WTAP mRNA to RPL4, which was associated with immune diseases. The nucleoprotein OGFOD1 catalyzed the hydroxylation of RPS23 and participated in the inflammatory process. The chromosome conformation confirmed the single nucleotide polymorphism function of IL23R genomic locus in AS disease. Conclusion:Ribosomal protein may be an important target for exploring the mechanism of AS inflammation.

Objective:To investigate the expression pattern,clinical significance,and the regulatory role of 2',5'-oligoadenylate synthetase 1(OAS1)in the proliferation of pancreatic ductal adenocarcinoma(PDAC)cells.Methods:Public databases such as Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)were used to analyze the expression of OAS1 in pancreatic cancer tissues.Immunohistochemical staining was applied to validate the expression level of OAS1 in PDAC tissue microarrays,and the association between OAS1 expression level and the prognosis of patients was analyzed.Real-time fluorescence quantitative PCR was performed to examine the expression level of OAS1 mRNA in different PDAC cell lines.CCK-8 assay and colony formation assay was used to assess the effect of OAS1 on the proliferation of PDAC cells after OAS1 silencing in Patu-8988 and PDC0034 cells by siRNA treatment.Further,Gene Set enrichment analysis(GSEA)was performed to screen for possible molecular mechanism of the regulatory role of OAS1 in PDAC.Cell viability and cholesterol level was analyzed after treatment with mTOR signaling activator MHY1485 in OAS1-silenced Patu-8988 and PDC0034 cells in order to verify the underlying mechanism of the regulatory role of OAS1 in PDAC cell proliferation.Results:Database analysis showed significant upregulation of OAS1 expression in pancreatic cancer tissues(P<0.05).Immunohistochemical staining results from PDAC tissue microarray showed that OAS1 expression was significantly upregulated in PDAC tissues compared with the paired paracancerous tissues,and high OAS1 expression was associated with poor prognosis(P<0.05).Real-time fluorescence quantitative PCR and Western blotting analysis show that OAS1 expression was higher in PDAC cells lines compared with normal ductal cells of the pancreas.The proliferative activity of PDAC cells decreased significantly after OAS1 silencing in Patu-8988 and PDC0034 cells(P<0.001).GSEA results indicated that OAS1 may affect PDAC cell proliferation through mTOR signaling pathway and cholesterol metabolism associated pathway.The mTOR signaling pathway may be inhibited and the total cellular cholesterol decreased after OAS1 silencing.Treatment with mammalian target of rapamycin(mTOR)activator MHY1485 partially reversed the inhibitory effect of OAS1 silencing on the proliferation and cholesterol metabolism of PDAC cells.Conclusion:OAS1 expression is upregulated in PDAC tumor tissues and cells and is associated with poor prognosis.OAS1 may promote the proliferation of pancreatic cancer cells by enhancing cholesterol metabolism through activation of the mTOR signaling pathway.

Objective:To investigate the expression pattern,clinical significance,and the regulatory role of 2',5'-oligoadenylate synthetase 1(OAS1)in the proliferation of pancreatic ductal adenocarcinoma(PDAC)cells.Methods:Public databases such as Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)were used to analyze the expression of OAS1 in pancreatic cancer tissues.Immunohistochemical staining was applied to validate the expression level of OAS1 in PDAC tissue microarrays,and the association between OAS1 expression level and the prognosis of patients was analyzed.Real-time fluorescence quantitative PCR was performed to examine the expression level of OAS1 mRNA in different PDAC cell lines.CCK-8 assay and colony formation assay was used to assess the effect of OAS1 on the proliferation of PDAC cells after OAS1 silencing in Patu-8988 and PDC0034 cells by siRNA treatment.Further,Gene Set enrichment analysis(GSEA)was performed to screen for possible molecular mechanism of the regulatory role of OAS1 in PDAC.Cell viability and cholesterol level was analyzed after treatment with mTOR signaling activator MHY1485 in OAS1-silenced Patu-8988 and PDC0034 cells in order to verify the underlying mechanism of the regulatory role of OAS1 in PDAC cell proliferation.Results:Database analysis showed significant upregulation of OAS1 expression in pancreatic cancer tissues(P<0.05).Immunohistochemical staining results from PDAC tissue microarray showed that OAS1 expression was significantly upregulated in PDAC tissues compared with the paired paracancerous tissues,and high OAS1 expression was associated with poor prognosis(P<0.05).Real-time fluorescence quantitative PCR and Western blotting analysis show that OAS1 expression was higher in PDAC cells lines compared with normal ductal cells of the pancreas.The proliferative activity of PDAC cells decreased significantly after OAS1 silencing in Patu-8988 and PDC0034 cells(P<0.001).GSEA results indicated that OAS1 may affect PDAC cell proliferation through mTOR signaling pathway and cholesterol metabolism associated pathway.The mTOR signaling pathway may be inhibited and the total cellular cholesterol decreased after OAS1 silencing.Treatment with mammalian target of rapamycin(mTOR)activator MHY1485 partially reversed the inhibitory effect of OAS1 silencing on the proliferation and cholesterol metabolism of PDAC cells.Conclusion:OAS1 expression is upregulated in PDAC tumor tissues and cells and is associated with poor prognosis.OAS1 may promote the proliferation of pancreatic cancer cells by enhancing cholesterol metabolism through activation of the mTOR signaling pathway.

Objective    To summarize the clinical result of a combined technical system for bicuspid aortic valve (BAV) repair. Methods    Patients who diagnosed as BAV and sever aortic regurgitation (AR) underwent a strategy of combined repair technics including annuloplasty, sinus plasty, leaflet plasty, sinus-tubular junction (STJ) plasty depending on anatomy pathological characteristics between October 2019 and January 2021 were enrolled. The clinical data of the patients were analyzed. Results    A total of 17 patients were enrolled. There were 11 males and 6 females with an average age of 18-49 (32.4±13.6) years. Fifteen patients had typeⅠand 2 patients had typeⅡBAV according to Sievers classification. Annuloplasty was applicated in 13 patients, sinus plasty in 8 patients, leaflet plasty in 17 patients, and STJ plasty in 11 patients, respectively. The cardiopulmonary bypass (CPB) time was 95 (84, 135) min, aortic cross-clamping time was 68 (57, 112) min, and the ICU stay time was 17 (12, 25) h. After the operation, mild AR was presented in 14 patients, moderate AR in 1 patient and severe AR in 2 patients. The latter 3 patients underwent second operation under CPB, after then, 1 patient had mild AR and 2 patients had moderate AR. The follow-up time was 13.1±4.6 months. At the latest follow-up, 12 patients had mild AR and 5 patients had moderate AR, and no patient had reoperation. Conclusion    A combined technical system for BAV repair can be used effectively and safely with an acceptable short and middle-term result.

Objective:To evaluate the mid-term outcomes of patients with rheumatic heart disease who underwent aortic valve repair surgery in a prospective cohort.Methods:From January 2016 to December 2020, a total of 54 patients with rheumatic heart disease underwent aortic valve repair surgery in Beijing Anzhen Hospital, with an average age of (50.61±13.29) years, including 29 females (53.7%). There were 31 patients (57.4%) had pure aortic insufficiency, 2 patients (3.7%) had pure aortic stenosis and 21 patients (38.9%) had mixed lesion. During the same period, 43 patients (80.0%) underwent mitral valve surgery, 36 patients (66.7%) underwent tricuspid valve surgery, and 20 patients (37.0%) underwent atrial fibrillation radiofrequency ablation.The follow-up period was from 1 month to 61 months (median follow-up was 25 months). Paired rank-sum test was used to compare the differences in continuous variables among subjects, and Kaplan- Meier method was used to analyze the clinical outcomes during the follow-up period. Results:Proportion of moderate and severe aortic regurgitation Preoperatively was higher than that of discharge data, aortic valve orifice maximum velocity and left ventricular end-diastolic diameter were significantly lower than discharge data (all P<0.05). The 5-year survival rate was (96.1±2.7)% (2 patients died). The 5-year freedom from reoperation after aortic valve repair was (89.5±4.5)%(5 patients underwent redo surgery). The 5-year freedom from valvular-related complications was (91.3±4.2)%(3 patients suffered from complications). Conclusion:Aortic valve repair surgery for rheumatic aortic valve disease is feasible and has excellent early and mid-term results, it can be a reliable treatment option.

Objective:To summarize the construction of a technics system of aortic valve repair in adult patients with aortic regurgitation(AR).Methods:From March 2013 to May 2020, aortic valve repair was performed in 79 patients. In which 43 cases underwent simple technics such as subcommissural annuloplasty, leaflet plication etc. Cases done before May, 2018 were defined as A group, yet the other 36 cases underwent a routine repair technics system including annuloplasty, sinusplasty, cuspidplasty and sinotubularplasty after then as B group. The general data and the operation procedure, also the follow-up were analyzed.Results:In group A, there were 2 cases with simple aortic valve repair and 41 cases with other intracardiac operations. In group B, 23 patients had aortic valve repair alone and 13 patients had other intracardiac operations. Group A mostly adopts the technologies of subjunctional involution and ridge suspension. In group B, flap ring molding, flap leaf molding, sinus tube joint molding and other technologies were used. Postoperative reflux was reduced to moderate or mild in most patients in group A. In group B, postoperative reflux was reduced to mild in most patients. There were 7 cases of severe reflux in group A, and 2 cases of severe reflux were worse after repair than before surgery. In group B, 8 patients had no effective repair, and 3 patients continued to have satisfactory repair after the second turnaround. Aortic regurgitation at 1 year(or the last echocardiographic follow-up) after surgery: 15 patients in group A were mild, 17 were moderate, and 4 were severe; In group B, 2 patients underwent revalve replacement within 1 year, and the remaining 29 patients were moderate and mild, 20 cases were moderate, 7 cases were moderate, and 2 cases were severe.Conclusion:In some adult moderate and severe AR cases, a routine combined repair system can be applied to increase success rate of repair, and shows a good short and mid-term result.

Objective:To compare the preliminary clinical effect of mitral valve replacement and mitral valvuloplasty on hypertrophic obstructive cardiomyopathy with mitral regurgitation.Methods:From January 2010 to December 2013, the patients undergoing cardiac surgery at Bakulev Cardiovascular Surgery Research Center in Russia were randomly divided into two groups: Forty-one patients received left ventricular outflow tract hypertrophy myocardial resection (Morrow operation) combined with mitral valve replacement (MVR) as MVR group; Forty-seven patients received Morrow surgery combined with mitral valve repair (MVr) as MVr group.The primary end point: death, secondary end point: thrombosis complications (cerebral infarction, peripheral arterial embolism), recurrence of mitral regurgitation and left ventricular outflow tract pressure difference were compared between the two groups.Results:In the MVr group, 6 cases were converted to MVR and were excluded from the study.The survival rates of MVR group and MVR group were 78.9% and 96.6%, respectively , and the thromboembolic free survival rates of MVR group and MVr group were 83.2% and 100%, respectively. The differences were statistically significant( P=0.034, 0.026, respectively). There was no significant difference in mitral regurgitation and left ventricular outflow tract pressure difference between MVR group and MVR group 24 months after operation( P=1.000, 0.934, respectively). Conclusion:Operation combined with MVR or MVr is an effective method to relieve left ventricular outflow tract obstruction and mitral regurgitation. Morrow operation combined with MVr can improve survival rate and reduce thrombosis complications.

Objective: To investigate the association of ambient fine particulate matters (PM_2.5) exposure with anxiety in middle-aged and elderly people in China. Methods: Using a stratified random sampling method, 5 997 middle-aged and elderly people (aged 40-89) who resided in the region for more than 2 years and had no hearing or language impairment were selected from 32 districts/counties in the key areas for air pollution prevention and control in China from October 10^th, 2017 to February 7^th, 2018. Information about demographic characteristics, socioeconomic factors and health status were collected by questionnaire survey and physical examination. The anxiety symptoms were assessed by 7-item Generalized Anxiety Disorder Scales. Three-year moving average concentrations of PM_2.5 were calculated to estimate exposure level. The multivariate logistic regression model was conducted to assess the association between PM_2.5 exposure and anxiety. The interaction of age, gender, overweight, education, smoking, drinking and chronic diseases was also analyzed by likelihood ratio test. Results: There were 2 995 (49.94%) males subjects, 4 092 (68.23%) subjects with education of secondary school or above and 2 576 (42.95%) subjects with self-reported chronic diseases among the 5 997 middle-aged and elder participants. The prevalence of anxiety was 6.64% (n=398). The mean±SD of 3-year moving average concentrations of PM_2.5, O₃ and SO₂ were (53.50±13.38), (90.58±13.26) and (40.29±12.56) μg/m³, respectively. PM_2.5 had significantly association with anxiety, and the corresponding OR value was 1.17 (95%CI: 1.05,1.31) with a 10 μg/m³ increment of 3-year moving average concentrations of PM_2.5. Compared with female (OR (95%CI)=1.07 (0.93,1.23)), those with no chronic diseases (OR (95%CI)=1.06 (0.93,1.20)) and those with primary school degree or below (OR (95% CI)=0.90 (0.75,1.09)), the association between PM_2.5 and anxiety was stronger among male (OR (95%CI)=1.35 (1.12,1.63)) and those with chronic diseases (OR (95%CI)=1.77 (1.31,2.38)), middle school education (OR (95%CI)=1.43 (1.22,1.67)), college education and above (OR (95%CI)=1.68 (1.05, 2.67)), all the P interaction values were <0.05. Conclusion PM_2.5 exposure has significantly positive association with anxiety. The associations are stronger in male, people with higher educational qualifications and patients with chronic diseases.