ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Background Although current evidence suggests a link between outdoor air pollution and depressive symptoms, the effect of solid fuel use (a significant indoor air pollutant) on depressive symptoms in China's rural middle-aged and elderly population remains poorly understood. Objective To explore the association between solid fuel use for cooking and depressive symptoms among middle-aged and elderly people in rural areas of China, and to provide a basis for the prevention and control of depressive symptoms among residents in rural areas. Methods Data were obtained from the 2020 China Family Panel Studies (CFPS), depressive symptoms were assessed using 8-item Center for Epidemiologic Studies Depression Scale (CES-D), and cooking fuel type was self-reported. Subsequently, two-level binary unconditional logistic regression models were fitted to assess the impact of solid fuel use for cooking on depressive symptoms. Results A total of 7991 participants aged 45 years and older [mean age (58.52±9.18) years] were included in the study, with a mean CES-D score of 6.07±4.48 and a mean positive depressive symptoms rate of 34% (40.54% in the solid fuel group and 30.81% in the clean fuel group, χ²=74.40, P<0.001). After controlling for potential confounding covariates, rural middle-aged and elderly residents in the solid fuel group had a higher risk of reporting depressive symptoms than those in the clean fuel group (OR=1.36, 95%CI: 1.20-1.54), an association that was unaffected by participant characteristics and was positive across age and gender groups. Conclusion There is a positive association between solid fuel use for cooking and depressive symptoms in middle-aged and elderly people in rural areas of China. It is recommended that rural areas promote the upgrading of stoves through the installation of ventilation equipment or the switch from solid cooking fuel to clean fuel. This approach is directed toward reducing exposure to household air pollution, alleviating the prevalence of depression among middle-aged and elderly residents in vast rural areas, and enhancing their mental health.

ObjectiveThis study aims to identify cuproptosis-related gene biomarkers in Alzheimer's disease（AD） using bioinformatics and machine learning methods， validate them at the clinical specimen level， and predict potential traditional Chinese medicine（TCM）. MethodsDifferentially expressed genes in the AD group and normal group were obtained using the Gene Expression Omnibus （GEO） database， and intersections were taken with reported cuproptosis-related genes to obtain differentially expressed cuproptosis-related genes. Machine learning methods were applied to identify core differential genes of cuproptosis in AD. Peripheral blood's single nucleated cells from clinical AD patients were collected， and the relative gene expression was clinically verified by real-time polymerase chain reaction（Real-time PCR）. Potential TCM regulating cuproptosis for AD were predicted by COREMINE database. ResultsA total of 12 cuproptosis-related genes were obtained， mainly involved in pathways of tricarboxylic acid cycle， 2-oxocarboxylic acid metabolism， and carbon metabolism. Five core cuproptosis-related genes， dihydrolipoamide dehydrogenase （DLD）， glutaminase （GLS）， pyruvate dehydrogenase E1 subunit beta （PDHB）， full name nuclear factor （erythroid-derived 2）-related factor 2 （NFE2L2）， and dihydrolipoamide branched-chain transacylase E2 （DBT） were finally screened using four machine methods. Thirty cases each of normal and AD patients were collected clinically. Compared with those in the normal group， minimum mental state examination （MMSE） and Montreal cognitive assessment （MoCA） were significantly decreased in the AD group （P<0.01）， Homocysteine（Hcy）， interleukin（IL）-6， C-reactive protein（CRP） ， and β amyloid protein（Aβ） indexes were significantly increased （P<0.01）， and malondialdehyde（MDA） indexes were decreased （P<0.05）. Superoxide dismutase（SOD） levels were significantly decreased （P<0.01）. The mRNA relative expressions of NFE2L2 and DBT were up-regulated （P<0.05）， and those of DLD， GLS， and PDHB were significantly down-regulated （P<0.01）. The TCM regulating cuproptosis-related genes for the treatment of AD were mainly based on the four Qi such as warmth， calmness， and cold， and the five flavors including bitterness， sweetness， and pungency， and it was attributed to the meridians of the liver， spleen， stomach， and kidney， with the efficacy of tonifying Qi， activating blood， eliminating phlegm， and resoling dampness. ConclusionDLD， GLS， NFE2L2， PDHB， and DBT can be used as novel diagnostic molecular markers for AD cuproptosis-related genes， and the corresponding potential therapeutic TCM can provide new ideas for the treatment of AD by TCM.

Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

Objective To investigate the expression of CD4+T cell subtypes and related inflammatory factors in patients with neutrophil-predominant frequent acute exacerbation chronic obstructive pulmonary disease(NE-FE-COPD).Methods COPD patients who were treated in the hospital from March 2019 to March 2021 were selected as the research objects.According to different phenotypes,they were divided into the infrequent exacerbator COPD group(IECOPD group,n=11),the eosinophilic dominant frequent acute plus severe COPD group(Eos-FE-COPD group,n=13),and the neutrophil dominant frequent exacerbator COPD group(NE-FE-COPD group,n=15).Patients with normal lung function and smoking history＞10 packs/year were the control group(CTRL group,n=9).Bronchoalveolar lavage fluid(BALF)was collected from each group,and the expression of CD4+T cell subtypes and inflammatory factors were detected by flow cytometry.The correlation between BALF and lung function and the frequency of acute exacerbation was ana-lyzed.CD4+CD28nullT cells and CD4+CD28+T cells were co-cultured with human airway epithelial cells(hAECs)and divided into co-culture group and Control group.The damage of hAECs was observed by immu-nofluorescence staining,and the mRNA and protein expression levels of ZO-1 and occludin were detected by RT-qPCR and Western blot.Results The proportion of CD4+CD28nullT cells and IL-1β level in BALF in the NE-FE-COPD group were higher than those in the CTRL group,the IE-COPD group,and the Eos-FE-COPD group,and the difference was statistically significant(P＜0.05).The proportion of CD4+CD28nullT cells and IL-1βlevel were negatively correlated with lung function(P＜0.05),and positively correlated with acute ex-acerbation frequency(P＜0.05).Compared with the Control group,hAECs tight junctions were damaged in the co-culture group,and mRNA and protein expression levels of ZO-1 and occludin decreased,with statistical significance(P＜0.05).Conclusion CD4+CD28nullT cells and IL-1β may be involved in the occurrence and de-velopment of NE-FE-COPD.

This article introduces the clinical approach and acupuncture characteristics of the traditional Chinese medicine practitioner Professor YU Hai-Bo in treating paediatric cerebral palsy using the"Jianpi Yishen Triple-Needle Grouping Acupoints".Guided by the theory of growth and development of"viscera-meridian-brain"growth and development,Professor YU believed that"insufficiency of spleen and kidney"is the core pathogenesis of paediatric cerebral palsy,and the treatment concept of"treating from the spleen and kidney"was proposed.He inherited and innovated the triple-needle grouping acupoints therapy and establishing the system of"Jianpi Yishen Triple-Needle Grouping Acupoints".Before regular acupuncture,the abdomen and dorsum are pricked to freely regulate the middle energizer,and the upper limbs are selected as"Hegu(LI4),Waiguan(SJ5),Quchi[(LI11),three acupoints on the hand]+ Neiguan(PC6)";the lower limbs are selected as"Zusanli(ST36),Sanyinjiao(SP6),Taichong[(LR3),three acupoints on the foot];"Shenmai(BL62),Zhaohai(KI6),Yongquan(KI1)",spleen and kidney are regulated simultaneously,and the head acupoints include Sishencong(EX-HN1),intelligence tri-needling,cerebral tri-needling,temporal tri-needling,mind-calming needling and bilateral Fengchi(GB20).In order to regulate the spirit and benefit the intellect,the matching acupoints are modified according to the disease and the syndromes.At the same time,it is supplemented with music therapy and auricular point seed-pressing.Emphasis is placed on the simultaneous regulation of"child-parent-doctor"and"treating the person"rather than the"treating the disease".

Objective To investigate the clinical efficacy of modified Fuzheng Yiliu Decoction(composed of Astragali Radix,Codonopsis Radix,Ligustri Lucidi Fructus,Hedyotis Diffusae Herba,Moutan Cortex,Visci Herba,etc.)combined with XELOX regimen(Oxaliplatin plus Capecitabine)for the treatment of postoperative patients with advanced gastric cancer of qi and yin deficiency type.Methods A total of 80 postoperative patients with advanced gastric cancer of qi and yin deficiency type were randomly divided into the Chinese medicine group and the control group,with 40 cases in each group.Both groups received chemotherapy with XELOX regimen,while the Chinese medicine group was given modified Fuzheng Yiliu Decoction.Three weeks constituted a course of treatment,the medication of Chinese medicine decoction lasted for two weeks or more in each course of treatment,and a total of 8 courses of treatment were performed.The incidence of adverse reactions during chemotherapy was monitored and changes in serum tumor markers of serum carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199)and alpha-fetoprotein(AFP)were observed in the two groups before and after treatment.Moreover,the patients'quality of life was assessed by the scores of Karnofsky's Performance Status(KPS)and World Health Organization Quality of Life Measurement Scale(WHOQOL-100).Long-term follow-up was carried out for the evaluation of the prognostic indicators such as overall survival and one-year and 2-year overall survival rates.Results(1)Patients in the two groups were all followed up,and the median follow-up time was 27 months(95%CI:23.59-27.86).(2)After treatment,the levels of serum CEA and AFP in the Chinese medicine group were significantly lower than those before treatment(P＜0.05 or P＜0.01),while serum CA199 tended to decrease compared with those before treatment,but the difference was not statistically significant(P＞0.05);in the control group,the levels of serum CEA,CA199,and AFP were not significantly decreased after treatment(P＞0.05).The intergroup comparison showed that the decrease of serum CEA,CA199 and AFP levels in the Chinese medicine group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)The adverse reactions during chemotherapy in the two groups mainly involved bone marrow suppression,gastrointestinal reactions and liver function abnormalities,etc.The incidences of all adverse reactions in the Chinese medicine group tended to be lower than those in the control group,but the differences were not statistically significant(P＞0.05).(4)After treatment,the KPS scores of patients in both groups were improved compared with those before treatment(P＜0.01),and the improvement in the Chinese medicine group was significantly superior to that in the control group(P＜0.01).(5)After treatment,the scores of the four dimensions of WHOQOL-100 such as health status,mobility,life feelings,and other activities of daily life in the Chinese medicine group were significantly improved compared with the pre-treatment(P＜0.05),whereas there was no significant improvement in the control group(P＞0.05).The intergroup comparison showed that the improvement of the scores of each dimension of the WHOQOL-100 in the Chinese medicine group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(6)The median survival in the Chinese medicine group was 29.0 months(95%CI:25.95-31.70)and that in the control group was 22.0 months(95%CI:19.67-25.58),indicating that the median survival was significantly prolonged in Chinese medicine group(P＜0.01).The one-year and 2-year postoperative survival rates were 97.5%and 77.5%in the Chinese medicine group and 92.5%and 47.5%in the control group,respectively.The intergroup comparison showed that the one-year and 2-year postoperative survival rates in the Chinese medicine group were higher than those in the control group(P＜0.01).Conclusion Modified Fuzheng Yiliu Decoction can effectively alleviate the adverse reactions during adjuvant chemotherapy for postoperative patients with advanced gastric cancer of qi and yin deficiency type,improve the quality of life of patients,and prolong the survival time of patients.

Objective To explore the severity of loneliness among the elderly in communities in Shanghai,and to identify factors associated with social and emotional loneliness respectively.Methods A cross-sectional study was conducted in older adults aged 65 years or above in Pudong New Area,Jing'an District and Huangpu District in Shanghai from Mar to Jun 2021.In Pudong New Area,multi-stage stratified random sampling was conducted based on the age and gender distribution of Shanghai,while in Huangpu District and Jing'an District convenience sampling was conducted.A total of 635 samples were included in the study.Loneliness was assessed using the De Jong Gierveld Loneliness Scale with social and emotional loneliness subscales.Logistic regression analyses were conducted to identify factors associated with social and emotional loneliness.Results Among the 635 participants,only 53 older adults(8.4%)were not lonely.Female(OR=0.46,95%CI:0.31-0.70),higher self-efficacy(OR=0.97,95%CI:0.94-1.00),more objective social support(OR=0.96,95%CI:0.93-0.99)were associated with less severe social loneliness.Meanwhile,higher level of education(secondary education,OR=0.56,95%CI:0.34-0.95;college or above,OR=0.30,95%CI:0.11-0.83)and higher self-efficacy(OR=0.96,95%CI:0.93-0.99)were associated with less severe emotional loneliness,while depression(OR=3.41,95%CI:1.76-6.60)and worse social capital(OR=2.02,95%CI:1.29-3.16)were associated with more severe emotional loneliness.Conclusion Up to 91.6%of the elderly in our study sample were moderately lonely or above.The factors associated with social loneliness include self-efficacy,gender and social support.The factors associated with emotional loneliness are self-efficacy,education level,depression,and social capital.

Objective To explore the role of endothelial cells in angiogenesis and myocardial remodeling in heart failure based on MAPKs pathway mediated by tumor endothelial marker 1(TEM1).Methods Sixty-four mice were equally randomized into four groups:sham operation,myocardial infarction(MI),MI+sh-NC and MI+ sh-TEM1.On the 7th day after MI,the changes of EndMT in the infarct border area were detected by immunofluo-rescence staining,and the cardiac function of mice was evaluated by echocardiography on the 28th day.Mouse aortic endothelial cells(MAECs)were divided into three groups:control,Vector and rTEM1.In addition,MAECs were pretreated with MAPK inhibitor SB203580,and the cells were treated with rTEM1 for 48 h.The changes of EndMT and MAPKs signaling pathways in endothelial cells were evaluated by Western blot.Results In the myocardium at the border of infarction,the level of TEM1-1 increased slightly on the 1st day after MI,reached the peak on the 7th day,and then decreased on the 28th day.Compared with Vector group,the expression of VE-Cadherin protein in the rTEM1 group decreased significantly(P<0.05),and the levels of α-SMA and vimentin,relative migration distance,the number of invading cells,and the number of branching formation increased signifi-cantly(P<0.05).SB203580 reversed these changes of MAECs induced by rTEM1.Compared with the MI group,the co-staining level of CD31+Vimentin+ in the MI+sh-TEM1 group decreased significantly(P<0.01).On the 28th day,the LVEF and LVFS in the MI+sh-TEM1 group were significantly higher than those in MI group(P<0.05).Compared with the MI group,the expressions of p-P38/P38 and p-JNK/JNK in the endothelial cells of the MI+sh-TEM1 group decreased.Conclusion EndMT and angiogenesis induced by TEM1 participate in the pathogenesis of cardiac fibroblasts induced by MI,which may be mechanically related to the activation of MAPKs signaling pathway.