ObjectiveTo analyze the influencing factors of pulmonary dysfunction among community-based population at high-risk for chronic obstructive pulmonary disease (COPD), and to establish a risk assessment model to provide a reference basis for accelerating the beforehand prevention and control of COPD and promoting the respiratory health of community-based residents. MethodsIndividuals aged >35 years old, with at least one risk factor except age illustrated in the Guidelines for Primary Diagnosis and Treatment of Chronic Obstructive Lung Disease (2018), and participated in the early screening for COPD from July 2022 to December 2023 were selected as the research subjects, and their lung function was assessed by the forceful expiratory volume in the first second after inhalation of bronchodilator (FEV₁)/ forced vital capacity (FVC) <70% and/or the ratio of FEV₁ to predicted value (FEV₁%Pred) <80% as the diagnostic criteria. In addition, risk factors related to pulmonary dysfunction were analyzed for the establishment of risk assessment model. ResultsA total of 823 individuals aged between 35‒76 years were included, among which 298 (36.21%) were diagnosed with pulmonary dysfunction, 167 (20.29%) with COPD, and 131 (15.92%) with preserved ratio but impaired spirometry. Logistic regression analysis revealed that male gender, increasing age, more frequent smoking, insufficient physical activity, recurrent wheezing, the presence of post-exercise wheezing or coughing, insensitive to airborne allergens, and history of chronic bronchitis or bronchial asthma were correlated with pulmonary dysfunction. The incidence rate of pulmonary dysfunction was 1.99 times higher in males than that in females, 1.81 times more common in those aged between 70‒76 years than those aged <60 years, 2.42 times more common in those who smoked 50‒200 pack-years than in those who smoked 0‒14 pack-years, 1.78 times higher in those who underwent physical activity <600 MET‑min·week^-1 than in those who underwent physical activity ≥600 MET‑min·week^-1, 2.61 times higher in those suffered recurrent wheezing than in those did not, 1.53 times higher in those with symptoms of post-exercise wheezing or coughing than in those without, 1.61 times higher in those insensitive to airborne allergens than those sensitive, 2.02 times higher in patients with chronic bronchitis than in those without, and 2.41 times higher in patients with bronchial asthma than in those without. The risk assessment model for pulmonary dysfunction constructed on this basis had a total score of 28 points, and the area under the subject operating characteristic (ROC) curve was 0.72, reaching the cut-off point of ROC curve while taking scores ≥10 points as the cut-off value for pulmonary dysfunction. ConclusionIn community-based high-risk COPD population, the incidence rate of pulmonary dysfunction is higher in males than that in females, in addition, which increases with the advancement of age. Smoking,insufficient physical activity,recurrent wheezing,post-exercise wheezing or coughing,insensitive to airborne allergens,and history of chronic bronchitis or bronchial asthma are high risk factors for pulmonary dysfunction. The risk assessment model constructed based on these factors has a good predictive effect in screening high-risk population of COPD, but its effectiveness in screening people at general risk needs to be further validated.

Objective To explore the effect of aerobic exercise on the activity of mammalian target of rapamycin(mTOR)signaling pathway in hippocampus of mice with different ages and its relation-ship with cognitive function.Methods Ninety one-month-old C57BL/6 male mice were randomly divid-ed into an aerobic exercise group(E,n=45)and a quiet control group(C,n=45).Group E was sub-jected to aerobic treadmill exercise with 75%VO2max intensity,while group C kept quiet.When they grew to 3,12 and 20 months,15 of them underwent Morris water maze test to test the cognitive func-tion before they were executed for their brain and hippocampus.Then,Western blotting was employed to detect the expression of mTOR,p-mTOR(Ser2448),p-S6K1(Thr389),p-4EBP1(Ser65)and brain-derived neurotrophic factor(BDNF),while immunohistochemical staining was used to detect BDNF pro-tein positive cells in the hippocampus and the integrated optical density was calculated.Results From day 3,the escape latencies in water maze navigation test of 12-month and 20-month mice were signif-icantly higher than the 3-month ones(P<0.05 or P<0.01),with those of the 20-month significantly higher than the 12-month(P<0.05 or P<0.01).Moreover,the distance in target quadrant and number of platform location crossing of the 12-month were significantly lower compared with the 3-month(P<0.05),while those of the 20-month mice were significantly lower than the 3-and 12-month(P<0.01).For 3-month old mice,p-mTOR(Ser2448),p-S6K1(Thr389),and p-4EBP1(Ser65)expressions in group E were significantly higher than group C(P<0.05 or P<0.01);but for the 12-and 20-month-old mice,p-mTOR(Ser2448),p-S6K1(Thr389),and p-4EBP1(Ser65)expressions in group E were significantly lower than those of the age-matched C groups(P<0.05 or P<0.01).Meanwhile,the ex-pression of BDNF in hippocampus of group E was significantly higher than the age-matched C groups(P<0.01).Conclusion Aerobic exercise can promote the development of cognitive function in young mice and delay the age-related degeneration in older mice,which may be realized by activating the hippocampal mTOR signaling pathway in young mice but inhibiting it in adult mice.It is suggested that the activity of mTOR signaling pathway is necessary for hippocampal memory in developing mice,but its overactivity may have adverse effects on cognition in elderly ones.

Objective To explore the effect of aerobic exercise on the activity of mammalian target of rapamycin(mTOR)signaling pathway in hippocampus of mice with different ages and its relation-ship with cognitive function.Methods Ninety one-month-old C57BL/6 male mice were randomly divid-ed into an aerobic exercise group(E,n=45)and a quiet control group(C,n=45).Group E was sub-jected to aerobic treadmill exercise with 75%VO2max intensity,while group C kept quiet.When they grew to 3,12 and 20 months,15 of them underwent Morris water maze test to test the cognitive func-tion before they were executed for their brain and hippocampus.Then,Western blotting was employed to detect the expression of mTOR,p-mTOR(Ser2448),p-S6K1(Thr389),p-4EBP1(Ser65)and brain-derived neurotrophic factor(BDNF),while immunohistochemical staining was used to detect BDNF pro-tein positive cells in the hippocampus and the integrated optical density was calculated.Results From day 3,the escape latencies in water maze navigation test of 12-month and 20-month mice were signif-icantly higher than the 3-month ones(P<0.05 or P<0.01),with those of the 20-month significantly higher than the 12-month(P<0.05 or P<0.01).Moreover,the distance in target quadrant and number of platform location crossing of the 12-month were significantly lower compared with the 3-month(P<0.05),while those of the 20-month mice were significantly lower than the 3-and 12-month(P<0.01).For 3-month old mice,p-mTOR(Ser2448),p-S6K1(Thr389),and p-4EBP1(Ser65)expressions in group E were significantly higher than group C(P<0.05 or P<0.01);but for the 12-and 20-month-old mice,p-mTOR(Ser2448),p-S6K1(Thr389),and p-4EBP1(Ser65)expressions in group E were significantly lower than those of the age-matched C groups(P<0.05 or P<0.01).Meanwhile,the ex-pression of BDNF in hippocampus of group E was significantly higher than the age-matched C groups(P<0.01).Conclusion Aerobic exercise can promote the development of cognitive function in young mice and delay the age-related degeneration in older mice,which may be realized by activating the hippocampal mTOR signaling pathway in young mice but inhibiting it in adult mice.It is suggested that the activity of mTOR signaling pathway is necessary for hippocampal memory in developing mice,but its overactivity may have adverse effects on cognition in elderly ones.

Objective:To investigate the correlation of the expression of Ephrin A receptor 2(EphA2)and its promoter region DNA hypomethylation with the occurrence of pyroptosis in invasive breast cancer. Methods:The expression level of pyroptosis-related protein EphA2 in normal breast tissue,paracancerous tissues and cancer tissues from 42 breast cancer patients was examined by Immunofluorescence staining and Western blotting.The expression level of pyroptosis related protein nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)was analyzed by immunofluorescence staining and Western blotting.The expression levels of apoptosis related proteins Caspase 1 and inflammatory cytokine interleukin-1β(IL-1 β)were studied by Western blotting.The DNA methylation level in the promoter region of EphA2 was investigated by nested methylation-specific PCR(nMS-PCR).The expression levels of DNA methyltransferase 1(DNMT1)and DNA methyltransferase 3a(DNMT3a)were examined by Western blotting.The correlation of the protein expression and methylation level of EphA2 in cancer tissues with the expression NLRP3,Caspase 1,IL-1 β,DNMT1 and DNMT3a was analyzed by Pearson correlation coefficient. Results:Compared with normal breast tissues and paracancerous tissues,the expression level of EphA2 protein was significantly increased(P＜0.01),while that of NLRP3,Caspasel and IL-1 βwas significantly decreased(P＜0.05)in breast cancer tissues.Meanwhile,compared with normal breast tissues and paracancerous tissues,the DNA methylation level of EphA2 promoter in breast cancer tissues was significantly decreased(P＜0.05),the expression level DNMT3a protein was significantly decreased(P＜0.01,P＜0.05),and the difference in the expression level of DNMT1 protein was not statistically significant.Pearson correlation analysis showed that the expression level of EphA2 protein is negatively correlated with that of NLRP3(r=-0.651 2,P＜0.05),Caspasel(r=-0.571 2,P＜0.05),IL-1β(r=-0.654 6,P＜0.05)or DNMT3a(r=-0.537 4,P＜0.05),while the methylation level of EphA2 was positively correlated with the protein expression level of NLRP3(r=0.634 1,P=0.026 8),Caspase1(r=0.672 8,P=0.01 6 5),IL-1 β(r=0.694 0,P=0.01 2 3)and DNMT3a(r=0.687 1,P=0.01 3 6). Conclusion:The expression of EphA2 protein is upregulated in breast cancer tissues is negatively correlated with pyroptosis.DNMT3a may be involved in the process of DNA hypomethylation in the promoter region of EphA2.

Objective:To investigate the effect of autophagy on the Treg/Th17 cell imbalance in mice with acute lung injury (ALI).Methods:Twenty-four male SD mice were randomly divided into the sham operation group (S group), sepsis group (Sep group) and autophagy inhibitor 3-methyladenine group (Sep +3-MA group). ALI model was prepared by LPS tracheal dripping method. The mouse pathological injury score mice were evaluated under light microscopy and the W/D ratio was calculated. The counts of Th17 cells and Treg cells in tracheoalveolar lavage fluid (BALF) of mice and the levels of related cytokines were detected by flow cytometry. The expressions of LC3-Ⅱ, Beclin-1 and p62 in Th17 cells and Treg cells in BALF were determined by Western blot.Results:CCompared with the S group, the lung histopathological score and W/D ratio of the Sep group and Sep+3-MA group increased ( P<0.05). Compared with the Sep group, the count of Th17 cells in BALF of the Sep +3-MA group decreased, while the count of Treg cells increased significantly with the progression of sepsis( P<0.05), and the levels of IL-17, IL-10 and TNF-α were significantly decreased ( P<0.05). TGF-β1 levels increased in the early stages of sepsis, but decreased significantly with the progression of sepsis( P<0.05). Compared with the Sep group, LC3-Ⅱ expression in BALF Th17 cells and Treg cells of the Sep+3-MA group showed a downward trend, but there was no statistical difference, while Beclin-1 expression significantly decreased ( P<0.05), and the expression of p62 significantly increased ( P<0.05). Conclusions:Abnormal activation of autophagy in Th17 cells and Treg cells is involved in the immune imbalance of Th17/Treg cells in ALI with sepsis. Inhibition of autophagy can restore the functions of Th17 cells and Treg cells, and improve the imbalance of Th17/Treg by inhibiting autophagy may become a new idea to control the pathogenesis and progression of immune disorders with sepsis.

Objective:To investigate the awareness and knowledge of influenza and vaccine among primary care providers in Shanghai.Methods:An online questionnaires survey was conducted by Shanghai Alliance for Respiratory Diseases in Primary Care from December 2017 to August 2018, healthcare providers in district central hospitals and community health care centers of Shanghai were invited to participate in the survey. The questionnaire contained the following items: the basic information of respondents; knowledge of influenza and its vaccine; current status of influenza vaccination; factors affecting promoting vaccination; the intention, attitude, perception of promoting vaccination and the influencing factors, and suggestions on promoting influenza vaccination.Results:A total of 1 542 valid questionnaires were collected, 88.3% (1 361/1 542) responders correctly recognized main symptoms of influenza; 58.2% (898/1 542) ignored the contact transmission of influenza; 41.6% (641/1 542) didn′t know the frequency of influenza vaccination; 82.7% (1 276/1 542) failed to recognize that pregnant women should also receive influenza vaccination. The survey showed that 31.2% (481/1 542) of responders had been vaccinated against influenza. The vaccination rate in community health care institutions was significantly higher than that in district central hospitals [39.1% (304/778) vs. 23.2% (177/764), χ 2=45.44, P<0.05]. Factors affecting vaccination for healthcare providers were: influenza antigen was variable, and vaccination had no effects [49.5% (404/816)]; the efficacy of the flu vaccine was doubt [48.8% (634/1 298)]; the vaccine wasn′t free [46.5%(604/1 298)]. The respondents believed that the main ways to improve the influenza vaccination were to formulate relevant national vaccination policies [79.7%(1 229/1 542)], to regularly publicize knowledge of influenza and influenza vaccine to residents through communities [65.8% (1 015/1 542)], and to recommend the patients by primary care medical staff [64.4% (993/1 542)]. Conclusion:Many healthcare providers have insufficient knowledge about influenza and vaccine. The vaccination rate of community health institutions is higher than that in district central hospitals in Shanghai. The willingness to promote influenza vaccination can be influenced by some factors. Increasing the willingness of healthcare providers might be helpful to improve the vaccination coverage among residents in the community.

OBJECTIVE: To analyze the molecular etiology of a Chinese child affected with dihydropyrimidinase deficiency. METHODS: Genomic DNA was extracted from peripheral blood samples of the family members. Pathogenic variant was determined by whole exome sequencing and verified by Sanger sequencing. RESULTS: The child was found to harbor homozygous c.905G>A (p.Arg302Gln) variants in exon 5 of the DPYS gene, for which her parents were both heterozygous carriers. CONCLUSION The homozygous c.905G>A (p.Arg302Gln) variants of the DPYS gene probably underlies the dihydropyrimidinase deficiency in the child. Above result has enabled genetic counseling and prenatal diagnosis for this family.
Amidohydrolases/genetics* ; Asian Continental Ancestry Group/genetics* ; Child ; Exons ; Female ; Humans ; Metabolism, Inborn Errors/genetics* ; Mutation ; Pedigree

Objective To compare the diagnostic accuracies of deep convolutional neural network (CNN) and dermatologists for pigmented nevus and seborrheic keratosis.Methods CNN network ResNet-50 was trained with 5 094 dermoscopic images of pigmented nevus and seborrheic keratosis using transfer learning,so as to establish a CNN two-classification model.Then,this model was applied to the automatic classification of 30 dermoscopic images of pigmented nevus and 30 dermoscopic images of seborrheic keratosis.Meanwhile,in combination with clinical photos of skin lesions,95 experienced dermatologists who had received dermoscopy training gave their diagnosis for the above 60 dermoscopic images.The diagnostic accuracies were compared between the two methods,and misclassified images were further analyzed.Results The CNN automatic classification model had the diagnostic accuracies of 100％ (30/30)and 76.67％ (23/30) for pigmented nevus and seborrheic keratosis respectively,and the total accuracy was 88.33％ (53/60).The average diagnostic accuracies of 95 dermatologists were 82.98％ (25.8/30) and 85.96％ (24.9/30) for pigmented nevus and seborrheic keratosis respectively,and the total accuracy was 84.47％ (50.7/60).There were no significant differences in the diagnostic accuracies for pigmented nevus or seborrheic keratosis between the CNN automatic classification model and 95 dermatologists (x2 =0.38,P ＞ 0.05).The dermoscopic images misclassified by CNN were divided into 3 categories:special-type lesions with high pigment content and marked keratosis,typical skin lesions with interference factors,and typical skin lesions without definite reasons for misclassification.Conclusions The performance of CNN automatic classification model is similar to that of experienced dermatologists in the two classification of pigmented nevus and seborrheic keratosis.The reasons for misclassification by CNN still need to be explored by dermatologists and professionals in artificial intelligence.

Objective To discuss the success rate of external cephalic version (ECV) for breech presentation in singleton pregnancies and the factors influencing ECV,and complications induced by ECV.Methods A prospective study was conducted which included 204 pregnant women who underwent regular prenatal examinations and delivered in Nanjing Drum Tower Hospital between March 1,2011 and February 29,2012.The 204 cases were single pregnancy with breech presentation identified by ultrasound during 32-37+6 weeks of gestation,and without other indications for cesarean section (CS).According to willingness of the participants,204 cases were divided into two groups.The 101 pregnant women who refused EVC (control group) were asked to practice knee-chest position twice a day; and 103 pregnant women volunteered to undergo EVC (ECV group) during 32-37+6 weeks of gestation.The proportion of cephalic presentation at delivery,CS rate and the incidence of PROM,premature delivery and cord around the neck were compared between the two groups.Factors influencing the success rate of ECV were analyzed.Chi-square or adjusted Chi-square test were used for statistical analysis.Results The proportion of cephalic presentation at delivery in the ECV group was higher than that in the control group [68.9％ (71/103) vs 29.7％ (30/101),x2=31.39]; the CS rate in the ECV group was lower than that in the control group [49.5％ (51/103) vs 78.2％ (79/101),x2=18.18],as was the rate of CS due to breech presentation [62.7％ (32/51) vs 89.9％ (71/79),x2=13.86],all P＜0.05.The success rates in frank breech presentation,complete breech presentation and incomplete breech presentation were 77.1％ (37/48),72.7％ (24/33) and 45.5％ (10/22),respectively (x2=7.37,P＜0.05),and the success rate in frank breech presentation was higher than that in incomplete breech presentation (x2=6.84,P＜0.017).No significant differences were observed in the success rates between primiparas and multiparas [67.7％ (63/93) vs 8/10,x2=0.19],placenta attached at front wall of uterus and other attachment sites [61.0％ (25/41) vs 74.2％ (46/62),x2=2.01],and EVC performed at 32-35+6weeks of gestation and 36-37+6 weeks [70.5％ (62/88) vs 9/15,x2=0.65],allP＞0.05.No significant differences were observed for the incidence of PROM [7.8％ (8/103) vs 6.9％ (7/101)],premature delivery [2.9％ (3/103) vs 2.0％ (2/101)] and cord around the neck [17.5％ (18/103) vs 21.8％ (22/101)] between the ECV and control group (x2=0.05,0.19 and 0.60,all P＞0.05).Conclusions ECV for breech presentation in singleton pregnancies can effectively correct the fetal position and reduce the CS rate.ECV performed after 32 weeks of gestation does not increase the risk of PROM and premature delivery.

0.05).Tumor volumes was diminished in group B and C as compared with that in group A(P