BACKGROUND: Despite some studies identifying a potential association between obesity and chronic obstructive pulmonary disease (COPD) risk, previous research had overlooked the dynamic nature of body weight over time, leading to inconsistent findings. The purpose of this study is to elucidate the relationship between adult weight change and COPD risk by adjusting for potential confounding factors. METHODS: We conducted a retrospective analysis using data from ten NHANES cycles (1999-2018), including adults aged 40-74 years. Weight change patterns were assessed using BMI at three time points and classified into five categories per period. Absolute weight change was also grouped into five levels. Multivariate logistic regression models, incorporating sampling weights, were used to examine associations between weight change and COPD, adjusting for demographic and lifestyle covariates. RESULTS: Compared with participants who maintained normal weight, stable obesity participants had increased risk of COPD from age 25 years to 10 years before the survey (OR = 1.45, 95% CI = 1.15 to 1.83), in the 10 years period before the survey (OR = 1.75, 95% CI = 1.47 to 2.08), and from age 25 years to survey (OR = 1.84, 95% CI = 1.46 to 2.31). Three periods indicate that weight gain in adulthood was associated with risk of COPD. In addition, substantial weight gain of more than 20 kg was associated with a higher risk of COPD. In stratified analyses, we also observed a more significant association between weight change and the risk of COPD in never smokers compared to former smokers. CONCLUSIONS Our study suggested that stable obesity and weight gain in adulthood were associated with an increased risk of COPD compared to those who maintain a normal weight, and that the association between weight gain and the incidence of COPD appears closer in patients who have never smoked.
Humans ; Pulmonary Disease, Chronic Obstructive/etiology* ; Middle Aged ; Male ; Female ; Adult ; Aged ; Retrospective Studies ; Weight Gain ; Obesity/complications* ; Risk Factors ; United States/epidemiology* ; Nutrition Surveys ; Body Mass Index

Objective:To evaluate the association between long-term exposure to ambient ozone (O 3) and sperm quality. Methods:From January 1, 2014, to December 31, 2019, healthy sperm donors were recruited through the Human Sperm Bank of Shandong University Affiliated Reproductive Hospital. A total of 37 977 sperm donation data from 2 971 healthy volunteers were analyzed. The average annual O 3 concentration (0.01°× 0.01°) was matched according to household address. A multivariate mixed-effect model was used to analyze the exposure-response relationship between the average O 3 exposure concentration and sperm quality in the previous year, with each donor as a random intercept. All results were presented as % changes with 95% confidence intervals ( CIs) for all sperm parameters associated with 10 μg/m 3 increases in O 3. The effects of individual characteristics on the association between O 3 and sperm quality were evaluated by stratified analysis. Results:The average O 3 concentration in the year before semen collection was (107.09±7.50) μg/m 3. Each 10 μg/m 3 increase in O 3 was associated with declined sperm concentration (-3.12%, 95% CI:-4.55%, -1.67%), total sperm count (-5.21%, 95% CI:-7.28%, -3.09%), total sperm motility (-1.49%, 95% CI:-2.37%, -0.61%), progressive motility (-2.53%, 95% CI:-3.78%, -1.26%), total motile sperm count (-5.82%, 95% CI:-8.17%, -3.41%), and progressively motile sperm count (-6.22%, 95% CI:-8.73%, -3.64%). Men aged 30 and above, obese, and with lower education levels might be more susceptible to the influence of O 3 on sperm quality, but the difference was not statistically significant ( P>0.05). Conclusion:Long-term exposure to O 3 in Shandong Province is associated with a decrease in sperm quality.

Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria bai-calensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of bio-physical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

With the proposal and development of new technologies, new methods, and new education theories, the research on medical education and teaching has been conducted extensively. The theories, methods, and management mode of the research on medical education and teaching are keeping pace with the times and thus promote the rapid improvement in teaching ability, medical talents, and the training level of medical humanities. However, current studies on medical education and teaching focus too much on the innovation of education theories, methods, and management and neglect the aspects such as educational ethics, student awareness, and assessment of potential benefits and risks. In addition, the lack of unified implementation and supervision standards in the whole process management of education research is also a problem that needs to be solved urgently, especially in empirical studies, which brings great challenges to the standardized implementation of education research. By performing an analogy with the clinical trial research system and summarizing education research and educational ethics, this study, for the first time, proposes a set of standardized and systematic medical education and research standards, including the paradigms of classification, staging and different stages. These standards provide a theoretical basis for implementing medical education research, improving the education compliance of target students, fully guaranteeing the benefits of target students, and avoiding the risks in education research, which provides a reference for standardized education research in other disciplines.

Purpose/Significance To reveal secondary infection knowledge related to infectious diseases by mining public literature data,and to promote the research and construction of the secondary infection monitoring platform,so as to improve the prevention and control level of infectious diseases in China.Method/Process The literature based discovery method is firstly adopted to mine and ana-lyze the secondary diseases from large-scale biomedical literature data,taking viral hepatitis,human immunodeficiency virus(HIV)infection and tuberculosis infection as the examples.Result/Conclusion 3 kinds of secondary diseases including infectious diseases,non-infectious diseases and even tumors,are found from more than 36.8 million PubMed literature.The research results not only validate that this method provides a new approach for systematically and comprehensively reveal secondary infection knowledge related to infectious diseases,but also provide more powerful literature evidences for effective monitoring and early intervention of secondary diseases.

It is found that acupuncture can significantly improve the clinical symptoms of rheumatoid arthritis (RA) such as pain and joint stiffness, and improve rheumatoid factor, high-sensitivity CRP, ESR and other clinical indicators. It can inhibit the proliferation of synovial cells, the apoptosis of chondrocytes, and regulate polarization balabce of mononuclear macrophages, T cells, as well as inhibit the inflammatory function of multiple immune cells, in order to improve inflammation state of RA joints. In clinical treatment of RA, bladder meridian, stomach meridian, spleen meridian , and Governor Vessel are mostly selected. Acupoints with the efficacy of warming meridian, dispelling coldness and dredging collaterals were commonly selected such as Zusanli (ST36), Yanglinquan (GB34), Dazhui (GV14), Quchi (LI11). Several researches have proved that combined therapy of acupuncture and medicine is worthy promotion in clinic.

Objective:To evaluate the association between long-term exposure to ambient ozone (O 3) and sperm quality. Methods:From January 1, 2014, to December 31, 2019, healthy sperm donors were recruited through the Human Sperm Bank of Shandong University Affiliated Reproductive Hospital. A total of 37 977 sperm donation data from 2 971 healthy volunteers were analyzed. The average annual O 3 concentration (0.01°× 0.01°) was matched according to household address. A multivariate mixed-effect model was used to analyze the exposure-response relationship between the average O 3 exposure concentration and sperm quality in the previous year, with each donor as a random intercept. All results were presented as % changes with 95% confidence intervals ( CIs) for all sperm parameters associated with 10 μg/m 3 increases in O 3. The effects of individual characteristics on the association between O 3 and sperm quality were evaluated by stratified analysis. Results:The average O 3 concentration in the year before semen collection was (107.09±7.50) μg/m 3. Each 10 μg/m 3 increase in O 3 was associated with declined sperm concentration (-3.12%, 95% CI:-4.55%, -1.67%), total sperm count (-5.21%, 95% CI:-7.28%, -3.09%), total sperm motility (-1.49%, 95% CI:-2.37%, -0.61%), progressive motility (-2.53%, 95% CI:-3.78%, -1.26%), total motile sperm count (-5.82%, 95% CI:-8.17%, -3.41%), and progressively motile sperm count (-6.22%, 95% CI:-8.73%, -3.64%). Men aged 30 and above, obese, and with lower education levels might be more susceptible to the influence of O 3 on sperm quality, but the difference was not statistically significant ( P>0.05). Conclusion:Long-term exposure to O 3 in Shandong Province is associated with a decrease in sperm quality.

Objective To explore the diagnosis of clinically suspicious von Willebrand disease(vWD)in a family and its pathogene-sis.Methods The pedigree information and the biological specimen were collected from the clinically suspected VWD patient and her family members(4 persons in total)in Peking University First Hospital.The levels of platelet count(PLT),activated partial thrombo-plastin time(APTT),vWF antigen(vWF:Ag),vWF activity(vWF:Ac)and FⅧ activity(FⅧ:C)were detected,and vWF risto-cetin cofactor(vWF:RCo)assay,ristocetin-induced platelet aggregation assay(RIPA)and vWF collagen binding(vWF:CB)assay were performed for phenotype diagnosis.The peripheral blood genomic DNAs were extracted from the proband and her family members to perform whole-exome sequencing for identifying the mutation of vWF gene,The mutation site was analyzed by using bioinformation tools to explore the pathogenesis of the proband.Results The APTT of proband(m 1)was slightly prolonged and her vWF:Ag,vWF:Ac,vWF:RCo and vWF:CB were significantly decreased.There was no obvious aggregation in RIPA assay(1.0 mg/mL and 1.25 mg/mL).In her father(Ⅱ3),APTT,FⅧ:C,vWF:Ag,vWF:Ac and vWF:CB were normal,but vWF:RCo was slightly decreased.In her mother(Ⅱ4),APTT,FⅧ:C,vWF:Ag,vWF:RCo and vWF:CB were all normal,but vWF:Ac significantly decreased.In her brother(Ⅲ2),APTT and FⅧ:C were normal,but vWF:Ag,vWF:Ac,vWF:RCo and vWF:CB were reduced to varying degrees.In all the family members(father,mother and brpther),no apparent aggregation in RIPA(1.0 mg/mL)was shown.Genetic analysis showed that the proband(Ⅲ1)carried a compound heterozygous mutation of vWF gene c.7288-9T＞G and c.1117C＞T,her father(Ⅱ3)carried vWF gene c.7288-9T＞G heterozygous mutation,and vWF gene c.1117C＞T heterozygous mutation was presented in both mother(Ⅱ4)and brother(Ⅲ2).Conclusion According to the results of laboratory tests,the proband was diagnosed as type 2A vWD.The hetero-zygous mutation in vWF gene c.1117C＞T and c.7288-9T＞G may be the molecular mechanism leading to type 2A vWD in the proband.

Objective:To compare the antiplatelet effects of vicagrel and clopidogrel in patients with different cytochrome P450 (CYP) 2C19 genotypes.Methods:This is a post-hoc analysis of a phase Ⅱ clinical trial of vicagrel, which included patients with coronary heart disease who underwent percutaneous coronary intervention from August 2018 to June 2019 in 18 centers. Patients were categorized based on the presence of CYP 2C19 *2 or *3 loss-of-function (LOF) alleles into LOF carrier group ( n=111) and non-LOF carrier group ( n=90). Each group included patients received vicagrel 5 mg, 6 mg, 7.5 mg, or clopidogrel 75 mg for 28 days per study protocol. P2Y 12 reaction units (PRU) were measured using VerifyNow at baseline, 6 to 8 hours after loading dose, 7 to 10 days after randomization, and 28 days after randomization and the percentage inhibition of platelet aggregation (%IPA) was calculated. The primary endpoint was %IPA on day 28. Within the patients from the General Hospital of Northern Theater Command, 8 to 12 patients in each study arms were enrolled in a prespecified pharmacokinetic sub-study, measuring the time to reach maximum plasma concentration (T max), peak plasma concentration (C max), and area under the plasma concentration-time curve (AUC). Results:Among 201 patients, the age was (58.8±8.5) years, and 139 (69.2%) were male. In non-LOF carriers, there was no significant differences in PRU values and %IPA between the vicagrel 5 mg, 6 mg, 7 mg, and clopidogrel groups at all time points (all P>0.05). In LOF carriers, %IPA was significantly higher in the vicagrel-treated groups than in the clopidogrel group at 6-8 hours after loading dose (22.9 (14.2, 31.5)% vs. 19.8 (11.0, 28.6)% vs. 29.5 (20.9, 38.0)% vs. 12.9 (3.9, 21.9)%, P=0.038) and 7-10 days after randomization (22.4 (14.2, 30.5)% vs. 34.4 (26.1, 42.6)% vs. 39.8 (31.8, 47.9)% vs. 24.7 (16.3, 33.2)%, P=0.001), with a trend towards higher %IPA in the vicagrel-treated groups at day 28 (30.4 (21.3, 39.6)% vs. 36.5 (27.2, 45.7)% vs. 40.8 (31.8, 49.8)% vs. 30.7(21.2, 40.2)%, P=0.056). Pharmacokinetic results of 35 patients showed that the C max and AUC of the active metabolite M15-2 of vicagrel was similar to that of clopidogrel in non-LOF carriers, but AUC between vicagrel 5 mg, 6 mg, 7 mg and clopidogrel were significantly different in LOF carriers ((5.6±0.6) h·μg -1·L -1 vs. (6.8±2.7) h·μg -1·L -1 vs. (9.2±3.3) h·μg -1·L -1 vs. (4.2±1.9) h·μg -1·ml -1, P=0.020). Conclusion:Vicagrel and clopidogrel have similar antiplatelet effects in non-LOF carriers, but vicagrel exhibits superior antiplatelet effects in LOF carriers.