Objective To investigate the epidemiological characteristics and risk factors of hyperhomocysteinemia(HHcy)in military aircrew.Methods A retrospective study was conducted on 506 aircrew convalescents undergoing health examination from September 2023 to April 2024.Demographic,lifestyle,and biochemical data were analyzed.The risk factors of HHcy were identified by x2 test and multivariate Logistic regression.Results The HHcy detection rate was 21.94%(111/506),with a median homocysteine(Hcy)level of 11.75(9.70-14.30)μmol/L.Multivariate analysis revealed that smoking(OR=2.093,95%CI:1.313-3.336),service in conventional fighter aircraft(OR=1.716,95%CI:1.063-2.770),elevated low-density lipoprotein cholesterol(LDL-C)(OR=2.510,95%CI:1.413-4.458),and elevated bilirubin(OR=2.360,95%CI:1.509-3.691)were independent risk factors for HHcy(all P<0.05).Conclusion There is a high prevalence of HHcy in military pilots.It is strongly associated with smoking,aircraft type,and metabolic abnormalities.It is recommended to incorporate Hcy testing into routine physical examination,implement risk factor-based stratified interventions,and establish an atherosclerotic cardiovascular diseases early warning system integrating vascular imaging and risk assessment,aiming to reduce cardiovascular risks and safeguard combat effectiveness.

Objective:To explore the correlation between post-traumatic stress disorder(PTSD),resilience and quality of life of front-line medical staff in public health emergencies.Methods:From Nov to Dec 2020,the medical staff of 4 COVID-19 designated hospitals in Wuhan were investigated with the general demographic questionnaire,10-item Connor-Davidson Resilience Scale,PTSD Checklist for DSM-5 and Simplify Qualify of Life Scale.Spearman correlation analysis and hierarchical regression analysis were used to investigate the correlation between PTSD,resilience and quality of life.Results:A total of 545 questionnaires were collected in this survey and the valid effective rate was 97.8% (533/545).The score of psychological resilience,PTSD and quality of life of medical staff were 26(20,30),17(8,25),and 20(18,23),respectively.And 13.1% (70/533)of medical staff had obvious PTSD symptoms.There were significant differences in the score of quality of life among medical staff with different genders,occupations and PTSD levels.Spearman correlation analysis results showed that the score of PTSD was negatively correlated with quality of life and psychological resilience(r=-0.488 and-0.464,P＜0.01).The score of psychological resilience was positively correlated with the score of quality of life(r =0.578,P＜0.01).Psychological resilience and PTSD were important predictors of quality of life,with an explanatory capacity of 37.0% .Conclusions:PTSD is a risk factor for quality of life,and psychological resilience is a protective factor for quality of life.In public health emergencies,improving psychological resilience,preventing and treating PTSD can improve the quality of life of medical staff.

BACKGROUND:The Yi people have used Sambucus adnata Wall to treat fractures,bruises,arthritis,etc.The author's group found that the active site aqueous extract(SAW-A)and dichloromethane extract(SAW-B)can promote fracture healing by promoting the expression of genes related to osteoblast proliferation,differentiation and maturation,differentiation and maturation.However,the therapeutic effect of methanol extract(SAW-C)at its active site on osteoarthritis is unclear. OBJECTIVE:To investigate the therapeutic effect of Sambucus adnata Wall extract on osteoarthritis,and to identify the effective targets of Sambucus adnata Wall extract in the treatment of osteoarthritis by network pharmacology technology. METHODS:A rat osteoarthritis model was replicated by anterior cruciate ligamentectomy and model rats were then treated with methanol extract of Sambucus adnata Wall by gavage for 21 days.On the 21st day after modeling,the knee joint of rats was detected by X-ray,the width of the knee joint was measured,oxidative stress indexes and inflammatory factors levels in serum and joint lavage fluid were detected,the morphology of the knee joint was observed by hematoxylin-eosin staining,full-thickness cartilage and hyaline cartilage thickness were measured,and the content of articular cartilage proteoglycan was observed by safranin O-fast green staining.The"drug-component-disease-target"network was constructed.Gene ontology enrichment analysis and Kyoto encyclopedia of genes and genomes enrichment analysis of effective targets were performed,and protein-protein interaction network maps were constructed using cytoscape software. RESULTS AND CONCLUSION:Sambucus adnata Wall extract could reduce tumor necrosis factor-α level in joint lavage fluid and serum levels of prostaglandin E2 and malondialdehyde,while increase the level of superoxide dismutase;relieve joint swelling caused by osteoarthritis;improve the histopathological state of articular cartilage,maintain the thickness of full-thickness articular cartilage,hyaline cartilage and the area of bone trabeculae in subchondral bone;and effectively prevent the loss of proteoglycans in articular cartilage and have a chondroprotective effect.Network pharmacological results showed that the methanol extract of Sambucus adnata Wall may have some targets related to inhibition of tumor necrosis factor,AKT1,interleukin-6,MAPK3,and SRC as well as inhibition of over-activation of EGFR signaling pathway and AGE-RAGE signaling pathway.

Objective To investigate the molecular mechanism of Shema Zhichuan Liquid in the treatment of neutrophilic asthma(NA)based on network pharmacology and in vivo experiments.Methods(1)The TCMSP,literature search and Swiss ADME and Swiss Target Prediction databases were used to search and screen the active components and their targets of Shema Zhichuan Liquid.OMIM,GeneCards,DisGeNET and DrugBank databases were used to search and screen NA disease-related targets.The intersection of the active components and NA disease-related targets of Shema Zhichuan Liquid was obtained through the microbiology platform to obtain the potential targets of Shema Zhichuan Liquid for the treatment of NA(common targets).Cytoscape 3.8 software was used to construct the network of"Chinese medicinals-active components-potential targets".The PPI network of potential targets was established by STRING database,and the core targets were obtained by analysing the built-in Mcode plug-in.The Metascape platform was used to enrich the gene ontology(GO),Kyoto Encyclopaedia of Genes and Genomes(KEGG)pathways for the potential targets.(2)BALB/C mice were acclimatised and fed for 1 week and randomly divided into a blank group,NA model group,low-dose group(2.5 g·kg-1)and high-dose group of Shema Zhichuan Liquid(10 g·kg-1),and control group of Dexamethasone(1 mg·kg-1);the NA mouse model was replicated by intraperitoneal injection of sensitizer(OVA+CFA)and nebulized inhalation excitation.OVA/CFA(20 μg OVA+75 μg CFA,0.3 mL)was injected intraperitoneally to sensitize on days 0,7 and 14 respectively,and 5%OVA suspension was nebulized on days 21-30(8 mL each time,40 minutes each time,once a day);1 hour before nebulisation,each group was administered by gastric gavage,and the Dexamethasone control group was administered by intraperitoneal injection once a day.The pathological changes of mouse lung tissue were observed by HE staining;IL-8 content in alveolar lavage fluid was detected by ELISA;mRNA expression levels of NLRP3 and CXCR2 were detected by RT-qPCR;and p-mTOR protein expression levels was detected by immunohistochemistry.Results(1)A total of 826 active component targets and 154 NA disease-related targets were obtained,and 51 potential targets(common targets)for the treatment of NA were obtained from the intersection of the active component and the NA disease-related targets of Shema Zhichuan Liquid.Through the network analysis of"Chinese medicinals-active components-potential targets",quercetin,lignocerotoxin,kaempferol,stigmasterol,naringenin and other key active components were obtained.The PPI network analysis of potential targets yielded 29 core targets,including AKT1,IL6,TNF,EGFR,NLRP3,RELA,MIF,CXCR2,VEGFA,etc..The GO functional enrichment analysis yielded 882 biological process entries,33 cellular component entries,and 61 molecular function entries;KEGG analysis yielded 142 signaling pathways,mainly involving TNF signaling pathway,influenza A signaling pathway,Toll-like receptor pathway,MAPK signaling pathway,mTOR signaling pathway and so on.(2)Results of animal experiments:compared with the blank group,mice in the NA model group showed obvious damage to the airway mucosa,structural disorders,a large number of inflammatory cells infiltration,mucosal congestion,oedema,obvious thickening of the alveolar wall,and narrowing of the alveolar lumen;the level of the inflammatory factor IL-8 in the alveolar lavage fluid was significantly elevated(P＜0.05);the mRNA expressions of NLRP3 and CXCR2 in the lung tissues of the mice were significantly up-regulated(P＜0.01),and the protein expression of p-mTOR was significantly increased.Compared with the NA model group,the structural arrangement of bronchial epithelial cells in the mice in the low-and high-dose groups of Shema Zhichuan Liquid was slightly disordered,with a small amount of inflammatory cell infiltration around the airways and blood vessels,and the congestion and edema of the bronchial mucosa were significantly reduced;the mRNA expression of CXCR2 in the lung tissues of the mice was significantly down-regulated(P＜0.01),and the level of expression of p-mTOR protein was significantly reduced.The IL-8 level in the vesicular lavage fluid of mice in the high-dose group was significantly reduced(P＜0.05);the mRNA expression of NLRP3 in the lung tissue of mice in the low-dose group was significantly down-regulated(P＜0.05).Conclusion The therapeutic effect of Shema Zhichuan Liquid on NA may be achieved through the key active components,such as quercetin,lignocerol and kaempferol,acting on the core targets,such as NLRP3 and CXCR2,and regulating the key signaling pathways,such as the TNF signaling pathway,the MAPK signaling pathway,the Toll-like signaling pathway,and the mTOR pathway.

Objective To investigate the effects of paeonol on the nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway and pyroptosis levels in ectopic lesion tissues of endometriosis(EMS)mice and mouse endometrial epithelial cells(mEECs).Methods An allograft transplantation method was used to establish an EMS mouse model.Thirty-five Balb/c mice were divided into a sham group,a model group,a 12.5 mg/kg paeonol group,a 25 mg/kg paeonol group,a 50 mg/kg paeonol group,a 0.5 mg/kg gestrinone group(positive control group),and a 50 mg/kg paeonol+Nrf2 inhibitor ML385(30 mg/kg)group,with 5 mice in each group.mEECs were divided into a cell control group,a 10 ng/ml transforming growth factor-β1(TGF-β1)or 100 ng/ml lipopolysaccharide(LPS)model group,a 50 μmol/Lpaeonol group,a 100 μmol/L paeonol group,and a 100 μmol/L paeonol+ML385 group.Enzyme-linked immunosorbent assay(ELISA)kits were used to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and IL-18 in the serum of EMS mice and the culture supernatant of mEECs.Hematoxylin and eosin(H&E)staining was used to detect histopathological changes in ectopic lesion tissues of mice.Western blot experiments were conducted to detect the protein expression levels of NOD-like receptor thermal protein domain-associated protein 3(NLRP3),apoptosis-associated speck-like protein(ASC),caspase-1,gasdermin D protein N-terminal fragment(GSDMD-N),Nrf2,heme oxygenase-1(HO-1),and quinone oxidoreductase-1(NQO-1)in ectopic lesion tissues and mEECs.The MTT method was used to detect the cell survival rate of mEECs,and the EdU staining method was used to detect the proliferation ability of mEECs.Wound healing assay and Transwell chambers were used to detect the migration and invasion abilities of mEECs,respectively.The FAM-FLICA? Caspase-1 kit was used to detect Caspase-1 levels in mEECs.AutoDock Vina software was used for molecular docking of paeonol with Nrf2 to evaluate their binding ability.Results Compared with the model group,the paeonol groups and the gestrinone group showed reduced ectopic lesion volumes in EMS mice(P<0.05),decreased serum levels of TNF-α,IL-6,IL-1β,and IL-18,decreased expression of pyroptosis marker proteins NLRP3,ASC,Caspase-1,and GSDMD-N in ectopic lesion tissues,and increased expression levels of Nrf2,HO-1,and NQO-1.Compared with the TGF-β1 model group,the paeonol group showed reduced proliferation,migration,and invasion abilities of mEECs.Compared with the LPS model group,the paeonol group showed decreased levels of inflammatory factors TNF-α,IL-6,IL-1β,and IL-18 in mEECs,decreased expression levels of NLRP3,ASC,Caspase-1,and GSDMD-N,and increased expression levels of Nrf2,HO-1,and NQO-1.In the EMS mouse model,the Nrf2 inhibitor ML385 reversed the inhibitory effects of 50 mg/kg paeonol on pyroptosis and inflammatory levels in ectopic lesion tissues.In the in vitro cell model,ML385 reversed the effects of 100 μmol/L paeonol on mEECs.The binding score of paeonol with Nrf2 was-6.1 kcal/mol,and paeonol formed hydrogen bonds with the VAL-604 and LEU-365 amino acid residues of Nrf2.Conclusion Paeonol can alleviate inflammatory responses in EMS mice,reduce NLRP3 inflammasome activation and pyroptosis levels in ectopic lesion tissues,and activate the Nrf2/HO-1 signaling pathway in ectopic lesion tissues of EMS mice.

Objective To investigate the effects of paeonol on the nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway and pyroptosis levels in ectopic lesion tissues of endometriosis(EMS)mice and mouse endometrial epithelial cells(mEECs).Methods An allograft transplantation method was used to establish an EMS mouse model.Thirty-five Balb/c mice were divided into a sham group,a model group,a 12.5 mg/kg paeonol group,a 25 mg/kg paeonol group,a 50 mg/kg paeonol group,a 0.5 mg/kg gestrinone group(positive control group),and a 50 mg/kg paeonol+Nrf2 inhibitor ML385(30 mg/kg)group,with 5 mice in each group.mEECs were divided into a cell control group,a 10 ng/ml transforming growth factor-β1(TGF-β1)or 100 ng/ml lipopolysaccharide(LPS)model group,a 50 μmol/Lpaeonol group,a 100 μmol/L paeonol group,and a 100 μmol/L paeonol+ML385 group.Enzyme-linked immunosorbent assay(ELISA)kits were used to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and IL-18 in the serum of EMS mice and the culture supernatant of mEECs.Hematoxylin and eosin(H&E)staining was used to detect histopathological changes in ectopic lesion tissues of mice.Western blot experiments were conducted to detect the protein expression levels of NOD-like receptor thermal protein domain-associated protein 3(NLRP3),apoptosis-associated speck-like protein(ASC),caspase-1,gasdermin D protein N-terminal fragment(GSDMD-N),Nrf2,heme oxygenase-1(HO-1),and quinone oxidoreductase-1(NQO-1)in ectopic lesion tissues and mEECs.The MTT method was used to detect the cell survival rate of mEECs,and the EdU staining method was used to detect the proliferation ability of mEECs.Wound healing assay and Transwell chambers were used to detect the migration and invasion abilities of mEECs,respectively.The FAM-FLICA? Caspase-1 kit was used to detect Caspase-1 levels in mEECs.AutoDock Vina software was used for molecular docking of paeonol with Nrf2 to evaluate their binding ability.Results Compared with the model group,the paeonol groups and the gestrinone group showed reduced ectopic lesion volumes in EMS mice(P<0.05),decreased serum levels of TNF-α,IL-6,IL-1β,and IL-18,decreased expression of pyroptosis marker proteins NLRP3,ASC,Caspase-1,and GSDMD-N in ectopic lesion tissues,and increased expression levels of Nrf2,HO-1,and NQO-1.Compared with the TGF-β1 model group,the paeonol group showed reduced proliferation,migration,and invasion abilities of mEECs.Compared with the LPS model group,the paeonol group showed decreased levels of inflammatory factors TNF-α,IL-6,IL-1β,and IL-18 in mEECs,decreased expression levels of NLRP3,ASC,Caspase-1,and GSDMD-N,and increased expression levels of Nrf2,HO-1,and NQO-1.In the EMS mouse model,the Nrf2 inhibitor ML385 reversed the inhibitory effects of 50 mg/kg paeonol on pyroptosis and inflammatory levels in ectopic lesion tissues.In the in vitro cell model,ML385 reversed the effects of 100 μmol/L paeonol on mEECs.The binding score of paeonol with Nrf2 was-6.1 kcal/mol,and paeonol formed hydrogen bonds with the VAL-604 and LEU-365 amino acid residues of Nrf2.Conclusion Paeonol can alleviate inflammatory responses in EMS mice,reduce NLRP3 inflammasome activation and pyroptosis levels in ectopic lesion tissues,and activate the Nrf2/HO-1 signaling pathway in ectopic lesion tissues of EMS mice.

Objectives:To investigate the effects of morning blood pressure on vascular endothelial function and chronic inflammatory response in the elderly.Methods:349 elderly people aged ≥60 who underwent 24-hour ambulatory blood pressure monitoring in Gaomi Municipal Hospital from April 2018 to October 2019 were selected to detect brachial artery flow mediated vasodilation (FMD) and chronic inflammatory factors [high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α) and interleukin (IL)-17] levels. According to the results of 24-hour ambulatory blood pressure monitoring, the subjects were divided into normal blood pressure group ( n=108), simple morning hypertension group ( n=114) and hypertension group ( n=127). The clinical data, 24-hour ambulatory blood pressure parameters, vascular endothelial function and inflammatory factors of the three groups were compared. The correlation between 24-hour ambulatory blood pressure parameters and FMD and inflammatory factors was analyzed by partial correlation. Results:Compared with the normal blood pressure group, the simple morning hypertension group and the hypertension group had lower FMD (all P<0.05), higher serum hsCRP and TNF-α , IL-17 levels (all P<0.05). Compared with the simple morning hypertension group, the hypertension group had lower FMD ( P<0.05), higher serum hsCRP, TNF-α and IL-17 levels (all P<0.05). After controlling for age, sex, smoking history, drinking history, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood glucose and 24 h average blood pressure, the morning systolic blood pressure was negatively correlated with FMD ( P<0.05), and positively correlated with serum hsCRP and TNF-α and IL-17 levels (all P<0.05); the morning diastolic blood pressure was negatively correlated with FMD ( P<0.05) and positively correlated with serum hsCRP and TNF-α levels (all P<0.05). Conclusions:Morning blood pressure level is closely related to vascular endothelial function and chronic inflammation level, and is independent of 24-hour average blood pressure. The increase of morning blood pressure may be an important risk factor for endothelial dysfunction and chronic inflammation in the elderly.

Parkinson′s disease is a degenerative disease of the central nervous system with abnormal protein deposition in the brain as the main pathological changes. The onset of Parkinson′s disease is related to abnormal deposition protein removal disorders, and the relevant mechanisms are still unclear. The glymphatic system is a metabolic waste and abnormal protein deposition removal system in the brain. In recent years, studies have shown that the changes of aquaporin 4, perivascular space and dural lymphatic vessels in Parkinson′s disease are closely related to the level of relevant pathological proteins in cerebrospinal fluid, leading to the occurrence and development of Parkinson′s disease. The researches on structure and biomarkers of the glymphatic system in Parkinson′s disease in recent years are reviewed in this article.

Based on the pharmacogenomics theory, this study developed a software system for interpretation of drug gene loci and guidance on clinical safe medication with the purpose of providing clinical guidance on the safety and effectiveness of drug use through accurate and efficient detection and interpretation of drug gene loci. The system infrastructure was built on a service-oriented architecture (SOA) design and Docker container virtualization approach to achieve a rapid and automatic interpretation of genetic results and best available drugs. The front end was established on HTML5 and JavaScript to realize visualization of analysis results and user interaction. The system was tested and validated to show robust performance which is reliable in clinical use. It will show high impact on the development of pharmacogenomics and clinical practice of patients with personalized medicine.
Humans ; Pharmacogenetics ; Precision Medicine ; Software

Objective To investigate the value of endoscopic retrograde appendicitis therapy ( ERAT) in the diagnosis and treatment of atypical acute appendicitis. Methods All the 48 patients suspected of atypical acute appendicitis in Jiangsu Province Hospital from January 2015 to December 2016 were randomly divided into ERAT group and conservative treatment group according to the treatment method. The final appendectomy rate of the two groups was analyzed. Results Only 17 of the 24 patients in the ERAT group received endoscopic treatment because of complex conditions or personal wishes, and 16 cases were diagnosed as acute appendicitis. Surgical resection was performed in 5 cases because of recurrence of the disease after ERAT, and the appendectomy rate was 31. 2％ ( 5/16 ) . In the conservative treatment group, all 24 patients were treated with antibiotics. Twenty of them underwent surgical resection with appendectomy rate of 83. 3％ ( 20/24) , and 1 of them had appendiceal perforation. The appendectomy rate of the ERAT group was significantly lower than that of the conservative treatment group (χ2=11. 111, P<0. 05) . Conclusion ERAT has a high diagnostic and therapeutic value for atypical acute appendicitis.