Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective:To establish a polymerase chain reaction(PCR)method to accurately discriminate the crude materials and aqueous extract of Zaocys dhumnades,Elaphe carinata,Elaphe meollendorff and Ptyas korros.Methods:Specific primers were designed using mitochondrial Cytb gene(CO1)as a target gene,and annealing temperature,number of cycles and the type of DNA polymerases were optimized.The mixed samples were detected by this method.Results:By this multiplex allele-specific PCR identification method,135,182,246 and 197 bp of specific fragments were amplified from DNA templates of Zaocys dhumnades,Elaphe carinata,Elaphe meollendorffi and Ptyas korros,respectively,following the conditions:cycle number of 35,annealing temperature of 62 ℃.The adulterants and the blank control showed no bands.The method could simultaneously and accurately identify the snake-derived components in the mixed samples.Conclusion:The method can be used to identify the samples of Zaocys dhumnades,Elaphe carinata,Elaphe meollendorffi and Ptyas korros simultaneously,accurately and rapidly,and is suitable for the identification of standard decoctiond and formula granules samples.

Objective In order to determine the incidence and mortality of uterine body cancer in Gansu province in 2019,the epidemic characteristics and the change trend of incidence and death from 2010 to 2019 were analyzed.Methods The quality control qualified data in Gansu province tumor registration center were used,uterine body cancer in urban and rural,age-specific inci-dence(mortality),the China standardized rate by Chinese population,the World standardized rate by World population,cumulative rate,crude incidence(mortality),composition ratio and rank,average annual percentage change(AAPC)and other indicators were calculated.Results In 2019,uterine body cancer in Gansu province ranked the seventh in the incidence of female malignant tumors,with a crude incidence of 4.43/100,000,the China standardized incidence was 3.28/100,000,and the World standardized incidence was 3.19/100,000.In 2019,uterine body cancer in Gansu province ranked the sixth among the mortality of female malignant tumors,with the crude mortality of 0.56/100,000,the China standardized mortality was 0.36/100,000,and the World standardized mortality was 0.35/100,000.The peak of morbidity(mortality)was in the age range of 50 to 54 years old.From 2010 to 2019,the incidence of uterine body cancer in Gansu province showed an overall upward trend.The China standardized incidence was AAPC=4.34%(95%CI:1.60%-7.15%),with a statistically significant trend(P<0.05);The mortality of uterine body cancer showed a fluctuating pat-tern of first rising,then decreasing,and increasing again,showing an overall downward trend.The China standardized mortality was AAPC=-11.35%(95%CI:-26.77%-7.32%),and the trend was not statistically significant(P>0.05).The incidence(mortali-ty)in rural areas was higher than that in urban areas.Conclusion The overall incidence of uterine body cancer in Gansu province is on the rise,and the death is on the decline.However,mortality in rural areas is on the rise.It is recommended to vigorously promote women′s health science popularization and education throughout the province,strictly implement the comprehensive measures of"early detection,early diagnosis,early treatment",and focus on the prevention and control of women aged 50-54,especially strengthening the early diagnosis and treatment of uterine body cancer in rural areas.

Objective:To compare the therapeutic effects of different inhaled medications on patients with frequent cough in chronic obstructive pulmonary disease (COPD), including changes in symptoms and acute exacerbation.Methods:This study was based on the RealDTC study, and the study subjects were stable COPD patients from the Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University from December 2016 to March 2023. The demographic characteristics, smoking status, history of biofuel exposure, history of acute exacerbation in the past year, lung function, COPD Assessment Test (CAT) score, modified British Medical Research Council Respiratory Difficulty Questionnaire (mMRC) score, and inhalation medication regimen of the patients were collected. Patients with frequent cough are defined as having a cough score of ≥2 in the first item of the CAT score. According to the type of inhaled medication, patients with frequent cough are divided into l long-acting muscarine anticholinergic (LAMA), long-acting β2 agonists (LABA)+ LAMA, inhaled corticosteroids (ICS)+ LABA, and ICS+ LABA+ LAMA groups. At the 6th month follow-up, CAT scores were collected and symptom control was evaluated, including minimum clinical improvement (MCID) (defined as a decrease of ≥2 points from baseline in CAT scores at the 6th month) and improvement in cough symptoms (defined as a decrease of ≥1 point from baseline in cough scores). During a one-year follow-up, the number of acute exacerbations was evaluated. The relationship between different inhaled medications and prognosis in patients with frequent cough in COPD was evaluated using multivariate logistic regression analysis.Results:A total of 653 patients with frequent cough in COPD were included, with a CAT score of (16.4±6.1) and a cough score of 3(2, 3). After 6 months of follow-up, 403 patients (61.7%) achieved MCID, and 394 patients (60.3%) had improved cough symptoms; During a one-year follow-up, 227 patients (34.8%) experienced acute exacerbation. After receiving inhalation medication treatment, the CAT scores and cough scores of four groups of patients with frequent cough, namely LAMA, LABA+ LAMA, ICS+ LABA, and ICS+ LABA+ LAMA, decreased compared to before treatment (all P<0.05). There was a statistically significant difference in the proportion of △CAT score, MCID, and acute exacerbation among the four groups of LAMA, LABA+ LAMA, ICS+ LABA, and ICS+ LABA+ LAMA (all P<0.05), while there was no statistically significant difference in the proportion of △cough score and cough score reduction ≥1 point (all P>0.05). The results of multivariate logistic regression analysis showed that compared with patients treated with LAMA or ICS+ LABA drugs, patients with frequent cough in COPD treated with LABA+ LAMA or ICS+ LABA+ LAMA drugs were more likely to achieve MCID and less likely to experience acute exacerbation (all P<0.05). Conclusions:Compared with LAMA or ICS+ LABA, patients with frequent cough in COPD who receive LABA+ LAMA or ICS+ LABA+ LAMA drug treatment are more likely to improve symptoms and have a lower risk of acute exacerbation.

Objective:To explore the impact of sleep disorders on the therapeutic effects of different inhaled medications in patients with chronic obstructive pulmonary disease (COPD).Methods:A prospective observational study was conducted on 393 patients with stable COPD who visited the Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University from December 2020 to September 2021. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality of patients with chronic obstructive pulmonary disease, and patients were divided into a non sleep disorder group and a sleep disorder group. The Berlin questionnaire was used to assess the risk of obstructive sleep apnea syndrome (OSAS) in patients, and the hospital anxiety and depression questionnaire (HADS) was used to assess the presence of anxiety and depression in patients. The improvement of symptoms [minimum clinically significant difference (MCID)] and the deterioration of symptoms [clinical significant symptom deterioration (CID)] within six months of patient follow-up were evaluated. The moderate to severe acute exacerbation of the patient was recorded during the one-year follow-up period. The clinical characteristics of two groups of patients were compared, and multiple regression analysis was used to evaluate the relationship between sleep quality and the prognosis of chronic obstructive pulmonary disease, as well as the impact of sleep disorders on the treatment efficacy of different inhaled drugs.Results:The average age of 393 patients with chronic obstructive pulmonary disease was (62.9±8.3)years old, with a median percentage of forced expiratory volume in the first second (FEV 1%) of 53.7%(30.7%) and a mean PSQI score of (5.7±3.4)points. 186 cases (47.3%) of patients had sleep disorders. Compared with patients in the non sleep disorder group, patients in the sleep disorder group had a higher proportion of middle school education and below, lower FEV 1 and FEV 1/forced vital capacity (FVC), higher baseline COPD Assessment Test (CAT), modified Medical Research Council (mMRC) and Clinical COPD Questionnaire (CCQ) scores, and a higher proportion of comorbid anxiety (all P<0.05). Compared with patients without sleep disorders, patients with sleep disorders had a lower incidence of MCID ( P=0.030) and a higher incidence of CID ( P=0.005). During the one-year follow-up period, patients with sleep disorders experienced a higher proportion of moderate to severe acute exacerbation ( P=0.001), severe acute exacerbation ( P=0.003), and frequent acute exacerbation ( P=0.009). The results of multiple regression analysis showed that patients with sleep disorders had a lower likelihood of developing MCID ( OR: 0.288, 95% CI: 0.145-0.379, P<0.001), and an increased risk of developing CID ( OR: 3.150, 95% CI: 2.011-4.388, P<0.001) and acute exacerbation ( OR: 1.659, 95% CI: 1.162-2.368, P=0.005). Compared with patients using long-acting muscarinic antagonist (LAMA) or inhaled corticosteroids (ICS)+ long-acting β2-agonist (LABA), patients in the sleep disorder group who used LABA+ LABA were more likely to develop MCID ( OR: 1.420, 95% CI: 1.021-2.751, P=0.010; OR: 1.976, 95% CI: 1.123-2.227, P=0.023). Conclusions:Compared with patients without sleep disorders, COPD patients with sleep disorders have a lower likelihood of symptom improvement, and a higher risk of symptom deterioration and acute exacerbation.Patients with COPD with sleep disorders are more likely to achieve symptom improvement by using LABA+ LAMA.

OBJECTIVE To investigate the effect mechanism of Gualou guizhi granule on neurological function and synaptic plasticity in rats with cerebral ischemia-reperfusion injury. METHODS The rats were randomly divided into sham operation group， model group and Gualou guizhi granule group （3.6 g/kg）， with 6 rats in each group. The cerebral ischemia-reperfusion injury model was established by the suture occlusion method. Two hours after modeling， the model rats were given relevant medicine or normal saline intragastrically， once a day， for 7 consecutive days. After the last medication， the neurological function of rats was evaluated [calculated by modified neurological severity scores （mNSS） and corner turning percentage]； the neuronal apoptosis rate of brain histiocyte in the ischemic side of rats was detected in each group； the positive expressions of growth associated protein 43 （GAP43） and microtubule associated protein 2 （MAP2） were detected； protein expressions of neuron-specific nuclear protein （NeuN）， synaptophysin-1 （Syn-1）， postsynaptic density protein-95 （PSD-95）， peroxisome proliferators-activated receptor γ （PPARγ）， brain-derived neurotrophic factor （BDNF） and tropomyosin receptor kinase B （TrkB）， as well as mRNA expressions of NeuN， Syn-1 and PSD-95 were detected. RESULTS Compared with the model group， mNSS， corner turning percentage and neuronal apoptotic rate were decreased significantly in Gualou guizhi granule group （P＜0.01）； GAP43 represented weak immunoreactivity， and MAP2 represented moderate immunoreactivity； protein expressions of NeuN， Syn-1， PSD-95， PPARγ， BDNF， TrkB and mRNA expressions of Syn-1， NeuN， PSD-95 were all increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Gualou guizhi granule can promote synaptic plasticity by activating BDNF/TrkB signaling pathway， thus playing a protective role in cerebral ischemia-reperfusion injury in rats.

Objectives To investigate the relationship between self-reported occupational noise exposure and levels of plasma inflammatory cytokines in asthmatic patients. Methods A total of 910 adult asthmatic patients were selected as the study subjects, and their occupational noise exposure history and other related information were collected. The peripheral blood samples were collected from the patients, and the expression levels of plasma soluble CD14 (sCD14), complement factor D (CFD), Eotaxin-11 (CCL11), and IL-9 were determined. The relationship between self-reported occupational noise exposure and the expression levels of the four inflammatory cytokines in patients’ plasma were analyzed using multiple linear regression models. The interactions between confounding factors and self-reported occupational noise exposure were further analyzed by interaction analysis. Results The plasma CCL11, sCD14 and CFD expressions in asthmatic patients with self-reported occupational noise exposure were significantly higher than those in patients without the exposure (P<0.05). After adjusting for confounding factors, compared with patients reporting no occupational noise exposure, the plasma CFD expression was increased by 0.17 (95% CI: 0.02, 0.31) natural logarithm units in patients with self-reported occupational noise exposure. During remission, the levels of plasma CCL11 and sCD14 in asthmatic patients with self-reported occupational noise exposure were increased by 0.27 (95% CI: 0.05, 0.49) and 0.22 (95% CI: 0.02, 0.41) natural logarithm units, respectively, when compared with patients without the exposure. Interaction analysis showed that self-reported occupational noise exposure had significant multiplicative interaction with smoking or pet ownership on plasma CCL11 or CFD expressions in asthmatic patients (all P<0.05). Conclusion Self-reported occupational noise exposure is significantly associated with increased expression levels of plasma CFD, CCL11, and sCD14 in adult asthmatic patients.

ObjectiveTo explore the effect of Ganoderma leucocontextum ethanol extract (GLE) on silicosis and its potential molecular mechanism using network pharmacology, molecular docking technology and animal experiments. Methods i) The components of GLE were analyzed using ultra-performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS) method. The active components, potential molecular pathways and targets of GLE in the intervention of inflammation process of silicosis was explored using network pharmacology and molecular docking technology. ii) Specific pathogen free male C57BL6/J mice were divided into four groups with 10 mice in each group. The mice in the silicosis model group and GLE intervention group were given a dose of 80 μL silica suspension with a mass concentration of 50 g/L once by non-exposed tracheal instillation, and the mice in the blank control group and GLE control group were given an equal volume of sterile 0.9% sodium chloride solution. From the second day after modeling, GLE control group and GLE intervention group were given GLE at a dose of 200 mg/(kg•d) by gavage, while blank control group and silicosis model group were given the same volume of 0.9% sodium chloride solution by gavage, once per day for 35 days. After that, the histopathological changes of lung tissues of mice were observed, the lung mass coefficient, inflammation score and the ratio of collagen deposition area were calculated, and the levels of tumor necrosis factor (TNF) -α, interleukin (IL) -1β and IL-6 in the lung tissues of mice were detected by enzyme-linked immunosorbent assay. Results i) A total of 76 active components of GLE were detected by UPLC-QE-MS. Among them, 36 ingredients met the screening criteria of the five principles of drug-like components. A total of 67 potential targets of the 36 GLE active ingredients to improve the inflammatory response of silicosis were screened based on the network pharmacology theory. The result of Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Ontology functional analysis showed that IL signaling and cytokine signaling of immune cells played a key role in the process of anti-silicosis of GLE. The results of molecular docking showed that the top 10 targets based on the 67 intersection targets were TNF, IL6, B-cell lymphoma 2, cellular tumor antigen p53, Caspase-3 subunit p12, JUN, epidermal growth factor receptor, IL1B, 67 kDa matrix metalloproteinase-9 and prostaglandin G/H synthase 2. The result of protein-protein interaction analysis showed that glycyrrhetinic acid had the strongest affinity with the key targets TNF-α, IL-1β and IL-6, followed by ganoderma acid DM, alismatol C, ganoderma acid β and red sapogenin. ii) The results of histopathological examination showed that the inflammatory response and collagen deposition were alleviated in the lungs of mice with silicosis. The lung mass coefficient, inflammation score, ratio of collagen deposition area and IL-6 expression in lung were lower in mice of the GLE intervention group (all P<0.05), compared with the silicosis model group. However, there was no significant difference in the levels of TNF-α and IL-1β in lung tissues between the two groups (all P>0.05). Conclusion GLE may reduce silica-induced lung inflammation and fibrosis by inhibiting the IL-6 level in lung tissues of mice. Its mechanism is associated with the synergistic action of multi-components, multi-targets and multi-pathways.

Objective To investigate the therapeutic mechanism of Pterocarya hupehensis Skan total flavonoids(PHSTF)for rheumatoid arthritis(RA).Methods Twenty-five male SD rats were randomly divided into normal control group,RA model group,PHSTF treatment(45 and 90 mg/kg)groups,and Tripterygium glycosides(TPG)tablet(10 mg/kg)group(n=5).Except for those in the normal control group,all the rats were subjected to collagen-induced arthritis(CIA)modeling using a secondary immunization method,after which PHSTF and TPG were administered via gavage once daily for 4 weeks.After the treatments,serum levels of TNF-α and IL-1β were measured using ELISA,and ankle joint pathologies were assessed with HE staining;the expression of citrullinated histone H3(Cit-H3),a neutrophil extracellular trap(NET)marker,in the ankle joints was evaluated with immunohistochemistry.In primary cultures of rat peripheral blood neutrophils stimulated with phorbol ester(PMA),the effects of PHSTF(100 and 200 μg/mL)on the expressions of Cit-H3,peptidylarginine deiminase 4(PADI4),neutrophil elastase(NE),and myeloperoxidase(MPO)were examined with Western blotting;immunofluorescence assay was used to observe Cit-H3 expression and NET formation in the cells.Results In the CIA rat models,PHSTF significantly alleviated ankle swelling,decreased serum levels of TNF-α and IL-1β,improved histopathological changes in the ankle joints,and reduced Cit-H3 expression in both the serum and ankle joint cartilage.In the isolated rat neutrophils,PHSTF showed no significant effect on cell viability but strongly inhibited PMA-induced NET release.Conclusion PHSTF can alleviate RA by inhibiting the formation of NETs.

Objective To investigate the MRI features of primary retroperitoneal leiomyosarcoma(PRLS).Methods Thirty-three cases of pathologically confirmed PRLS were analyzed retrospectively,and their multi-parameter MRI features were analyzed qualitatively and quantitatively.Results Of the 33 PRLS,24 cases were located in the renal hilum,inferior vena cava,or the area around the bifurcation of the iliac vessels.Twenty-four cases had relatively intact capsule,25 cases had necrosis,and 15 cases had coagulated geographic necrosis.The mean diameter of the tumors was(9.9±5.1)cm,ranging from 3.0 to 20.7 cm,among which 27 cases with a diameter larger than 5 cm.The tumor parenchyma of the 33 PRLS all showed significantly high signal intensity on diffusion weighted imaging(DWI),and significantly low signal intensity on apparent diffusion coefficient(ADC)map.The tumor parenchyma showed moderate to obvious degree of progressive enhancement,and the signal intensity value of the tumor in each phase after contrast injection was higher than that of the psoas major muscle(P＜0.001).Conclusion PRLS are usually large but have a relatively intact capsule and are closely related to the major retroperitoneal veins.The coagulated geographic necrosis,significantly limited diffusion of water molecules,and progressive enhancement pattern all show certain MRI characteristics.