Background With the aging of China's population, cognitive impairment in the elderly is receiving increasing public attention. Screening and intervention of people with mild cognitive impairment (MCI) are of great significance to prevent and reduce the occurrence of cognitive impairment. Objective To understand the prevalence and explore potential influencing factors of MCI in the elderly in Songjiang District, Shanghai, and to provide scientific basis for promoting early screening of cognitive impairment and precise intervention of MCI in the elderly in this area. Methods A cross-sectional study design was adopted. From August to October 2022, using multi-stage random sampling, 1800 elderly residents aged 60 years and above were screened for cognitive impairment in 6 neighborhood/village committees in 6 towns in Songjiang District. The survey questionnaires included a sociodemographic questionnaire, a health status and lifestyle questionnaire, the Instrumental Activities of Daily Living (IADL), the Patient Health Questionnaire (PHQ-9), and the Mini-Mental State Examination (MMSE). Prevalence rates of MCI among the elderly by selected social demographic characteristics, health status, and lifestyle were estimated, and potential influencing factors of MCI were evaluated by binary logistic regression. Results A total of 209 elderly residents with MCI and 1591 healthy elderly residents were detected, and the prevalence of MCI in the elderly aged 60 and above was 11.6% in Songjiang District. Being physically active (OR=0.556, 95%CI: 0.399, 0.774) reduced the risk of MCI. Illiteracy (OR=1.810, 95%CI: 1.239, 2.644), primary school education level (OR=3.454, 95%CI: 2.342, 5.092), non-participation in social activities (OR=1.945, 95%CI: 1.360, 2.781), IADL damaged (OR=3.173, 95%CI: 2.137, 4.712), and depression (OR=1.957, 95%CI: 1.112, 3.443) increased the risk of MCI (P＜0.05). Conclusion The prevalence of MCI among the elderly in Songjiang District is lower than the national average. Educational level, physical activity, participation in social activities, IADL, and depression may be the influencing factors of MCI in the elderly. It is recommended to carry out early screening, early detection, and early intervention for cognitive impairment in the elderly. Improving involvement in physical exercise and increasing participation in social activities are encouraged. Special attention should be paid to the needs of vulnerable groups such as low education level and disabled elderly during a community MCI intervention program.

Objective To compare the effects of the left and right stellate ganglion resection on myocardial injury in rats with acute myocardial infarction(AMI).Methods According to the random number table method,30 healthy male Sprague Dawley rats were divided into the AMI group,left stellate ganglionectomy group,and right stellate ganglionectomy group,with 10 rats in each group.AMI models were prepared by ligation of the left anterior descending branch of the coronary artery in all the three groups.In the AMI group,the stellate ganglion was isolated(randomly left or right)without excision.The rats in the left and right stellate ganglionectomy groups underwent the left and right stellate ganglionectomy,respectively.At 24 hours after modeling,2 mL of subclavian venous blood was extracted from the three groups of rats.The serum levels of cardiac troponin Ⅰ(cTnⅠ),noradrenaline(NE),interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),malondialdehyde(MDA),and superoxide dismutase(SOD)were detected by enzyme-linked immunosorbent assay.The left ventricular fractional shortening(LVFS),left ventricular ejection fraction(LVEF)and cardiac output(CO)of rats in the three groups were measured by echocardiography one week after modeling.Results The serum levels of NE,cTnⅠ and MDA in the left and right stellate ganglionectomy groups were significantly lower than those in the AMI group,and SOD level was significantly higher than that in the AMI group(P＜0.05);the serum levels of NE,cTnⅠ and MDA in the right stellate ganglionectomy group were significantly lower than those in the left stellate ganglionectomy group,and SOD level was significantly higher than that in the left stellate ganglionectomy group(P＜0.05).The levels of serum IL-1β,IL-6 and TNF-α in the left and right stellate ganglionectomy groups were significantly lower than those in the AMI group(P＜0.05);the levels of serum IL-1β,IL-6 and TNF-αin the right stellate ganglionectomy group were significantly lower than those in the left stellate ganglionectomy group(P＜0.05).LVEF,LVFS and CO in the left and right stellate ganglionectomy groups were significantly higher than those in the AMI group,and LVEF and LVFS in the right stellate ganglionectomy group were significantly higher than those in the left stellate ganglionectomy group(P＜0.05);there was no significant difference in CO between the left and right stellate ganglionectomy groups(P＞0.05).Conclusion Stellate ganglionectomy has a protective effect on AMI induced by ligation of the left anterior descending branch of the coronary artery,which may be related to reducing inflammatory reaction and oxidative stress damage.The right stellate ganglion resection has more protective effects on cardiac function than the left stellate ganglion resection.

Objective To investigate the effects of lumbar epidural block of renal sympathetic nerve on cardiac function and serum inflammatory factors in rats with myocardial infarction.Methods Thirty healthy male Sprague Dawley rats were divided into asham operation group,myocardial infarction group and sympathetic nerve block group according to the random number table method,with 10 rats in each group.Lumbar epidural catheterization was applied in all rats in the 3 groups.After catheter insertion,myocardial infarction was induced by ligation of the anterior descending branch of the left coronary artery of rats in the myocardial infarction group and the sympathetic nerve block group,while the left anterior descending branch of rats in the sham operation group was not ligated.After myocardial infarction,the rats in the sympathetic nerve block group were injected with 50 μL of ropivacaine(volume fraction:0.2％)via a lumbar epidural catheteronce every 24 hours,and the injection lasted until 14 days after surgery.In the myocardial infarction group,50 μL of 9 g·L-1sodium chloride was injected into the rats through a lumbar epidural catheteronce every 24 hours,and the injection lasted until 14 days after surgery.Rats in the sham group did not receive the injection of any drugs.At 14 days after operation,echocardiography was performed on rats in the 3 groups to measure ejection fraction(EF),left ventricular short-axis shortening rate(FS)and cardiac output(CO).A total of 1 mL of cervical venous blood was extracted from each rat in the 3 groups at 24 h after surgery,and 5 mL of abdominal aortic blood was extracted from rats in the 3 groups at 14 days after surgery.Serum levels of norepinephrine(NE),cardiac troponin I(cTnl),interleukin-18(IL-18),interleukin-1β(IL-1 β)and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay.At 14 days after surgery,the rats in the 3 groups were anesthetized by intraperitoneal injection of 100 g·L-1 chloral hydrate(300 mg·kg-1),and the thoracic cavity of the rats was opened to remove the heart.The myocardial infarction area of the rats was detected by 2,3,5-triphenyltetrazolium chloride staining,and the proportion of the myocardial infarction area was calculated.Results On the 14th day after surgery,EF,FS and CO of rats in the myocardial infarction group and sympathetic nerve block group were significantly lower than those in the sham operation group,while EF,FS and CO of rats in the sympathetic nerve block group were significantly higher than those in the myocardial infarction group(P＜0.05).The serum cTnI level of rats in the myocardial infarction group and sympathetic nerve block group was significantly higher than that in the sham operation group(t=68.260,15.110;P＜0.05),and the serum cTnI level of rats in the myocardial infarction group was significantly higher than that in the sympathetic nerve block group(t=27.920,P＜0.05).The proportion of the myocardial infarction area of rats in the sympathetic nerve block group was significantly lower than that in the myocardial infarction group(t=14.182,P＜0.001).There was no significant difference in the serum NE,IL-18,IL-1 β and TNF-α levels of rats between 24 hours and 14 days after surgery in the sham operation group(P＞0.05).The serum NE,IL-1 β and TNF-αlevels of rats at 14 days after surgery were significantly higher than those at 24 hours after surgery,and the IL-18 level of rats was significantly lower than that at 24 hours after surgery in the myocardial infarction group(P＜0.05).The serum NE,IL-18 and TNF-α levels of rats at 14 days after surgery were significantly lower than those at 24 hours after surgery,and the IL-1 βlevel of rats was significantly higher than that at 24 hours after surgery in the sympathetic nerve block group(P＜0.05).At 24 hours and 14 days after surgery,the serum NE,IL-18,1L-1 β and TNF-α levels of rats in the myocardial infarction group and sympathetic nerve block group were significantly higher than those in the sham operation group,while the serum NE,IL-18,IL-1 β and TNF-α levels of rats in the sympathetic nerve block group were significantly lower than those in the myocardial infarction group(P＜0.05).Conclusion Lumbar epidural block of renal sympathetic nerve in rats can significantly reduce the levels of serum inflammatory factors and NE,and improve cardiac function.

With the rapid development of clinical trials, the relevant medical research and molecular detection based on biological samples are closely related to the progress of clinical trials, making the role of biological samples in clinical trials increasingly obvious. The standardized supervision mode of biological samples is an important prerequisite for carrying out high-quality clinical trials. Although the laws and regulations related to clinical trials are becoming more and more perfect, there are still a large number of adverse events related to biological samples, which seriously affects the progress and results of clinical trials, and is one of the important challenges currently facing. Therefore, it is urgent to enhance the supervision of biological samples and improve the management methods of biological samples in clinical trials at this stage. Through in-depth discussion of the current status of biological sample management in clinical trials at home and abroad, this paper analyzed the issues existed during the supervision of biological samples, and supplemented the biological sample management methods by further combing the existing relevant laws and regulations and the Guidelines for the Ethical Management of Biological Samples in Clinical Trials, with a view to providing suggestions and ideas for optimizing the management mode of biological samples in clinical trials.

Objective:To analyze the antimicrobial resistance and genomic characteristics of Salmonella enterica serovar Derby strains isolated from human and food sources in Hangzhou. Methods:A total of 60 Salmonella enterica serovar Derby strains isolated in Hangzhou during the period from 2015 to 2020 were subjected to antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE) typing and whole-genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and the identification of antimicrobial resistance genes were performed using the sequencing data. Phylogenetic tree based on the single nucleotide polymorphism (SNP) sites in the 60 genomes from Hangzhou and 379 genomes from public databases was constructed. Results:No significant difference was observed in the drug resistance rates between the clinical strains and food strains in Hangzhou. The multidrug resistance (MDR) rate was 76.7% (46/60). All of the 60 Salmonella Derby strains were positive for the antimicrobial resistance genes aac(6′)- Iaa and fosA7. The 60 strains were subtyped into 46 molecular types by PFGE and 53 molecular types by cgMLST(HC2). Except for one strain belonging to ST3220, the other Salmonella Derby strains were ST40. The phylogenetic analysis showed that some strains isolated in Hangzhou were close to the strains in Southeast Asia, suggesting the possibility of cross-border transmission of ST40 strains, with the main food sources being pork and fish; other strains were close to those circulating in Beijing, Guangzhou, Hubei, Chongqing and other provinces, suggesting the possibility of cross-province transmission of the strains, with the main food sources being pork, beef and chicken. Conclusions:The epidemic of Salmonella Derby in Hangzhou was mainly caused by the spread of ST40 strains and MDR was common. Clinical infections might be closely related to the consumption of pork, beef, chicken and fish. There was the possibility of cross-border transmission of Salmonella Derby between Hangzhou and Southeast Asia and cross-province transmission in China.

Objective:To preliminarily evaluate the immunogenicity and efficacy of two novel tuberculosis vaccine candidates (a fusion multicomponent protein EPDPA015f and a mixed multicomponent protein EPDPA015m) and to provide a new antigen combination for the development of tuberculosis vaccines.Methods:Recombinant plasmids for the expression of EPDPA015f and EPDPA015m proteins were constructed. Six-week-old BALB/c mice were immunized with EPDPA015f or EPDPA015m in combination with aluminium adjuvant (50 μg/mouse) for three times with an interval of 10 d. The mice were sacrificed 10 d after the last immunization to collect blood and spleen samples. Serum antibody titers and cytokine levels were measured by ELISA, Luminex technique and enzyme-linked immunospot assay (ELISPOT). Mycobacterial growth inhibition assay (MGIA) was used to detect the ability of mouse splenocytes to inhibit the growth of Mtb in vitro. One-way analysis of variance and t-test were used for statistical analysis. Results:Both EPDPA015f and EPDPA015m could induce the production of various cytokines and IgG antibodies at a high level. The levels of cytokines related to Th1 (IL-2, TNF-α, IFN-γ), Th2 (IL-4, IL-6, IL-10) and Th17 (IL-17) as well as other proinflammatory cytokines (GM-CSF, IL-12) were higher in the EPDPA015f group than in the adjuvant group ( P<0.05). The titer of IgG antibody induced by EPDPA015f was as high as 1∶4×10 6. The results of MGIA showed that the numbers of Mtb (lgCFU) in the PBS, adjuvant, EPDPA015f and EPDPA015m groups were 3.46±0.11, 3.51±0.06, 2.98±0.09 and 3.19±0.08, respectively. The number of colonies in the EPDPA015f group was the least as compared with that in the other three groups ( P<0.001, P<0.001, P<0.01). Conclusions:The vaccine candidate EPDPA015f could elicit more comprehensive and high-level cellular and humoral immune responses, and exhibited superior in vitro inhibitory activity against the growth of Mtb. EPDPA015f had the potential to be used as a preventive vaccine or a booster vaccine

Purpose To investigate the clinicopathological characteristics and genetic variations of stage Ⅰ lung adenocarci-noma with high-grade components,according to the new grading system of the WHO classification of thoracic tumors(2021).Methods A retrospective analysis was conducted on the clini-cal data of 785 patients with stage Ⅰ lung adenocarcinoma.HE,EnVision immunohistochemistry and Victoria blue staining were used,common genetic variation(EGFR/KRAS/ALK/ROS1/RET)were detected by PCR method.The correlation between different high-grade components and clinical pathological charac-teristics as well as genetic variations in stage Ⅰ lung adenocarci-noma were analyzed.Results A total of 785 cases of stage Ⅰlung adenocarcinoma were enrolled,including 332 cases with high-grade components and 453 cases without high-grade compo-nents.Among the adenocarcinomas with high-grade components,there were 7 cases of grade 1,150 cases of grade 2,and 175 ca-ses of grade 3.The positive rates of tumor cells spreading through airspace(STAS),vascular invasion,and pleural inva-sion in grade 2 adenocarcinoma with two high-grade components(61.5％,21.2％,26.9％)were significantly higher than that of the adenocarcinomas with only one high-grade component(20.4％,7.1％,5.1％),but there was no significant differ-ence in grade 3 adenocarcinoma.The positive rate(39.0％)of STAS in the micropapillary group with one high-grade component in grade 2 adenocarcinoma was significantly higher than that in the complex glandular group(9.3％)and the solid group(0),while there was no significant difference between the latter two groups.Among the three groups there were no statistically signif-icant differences in grade 3 adenocarcinoma.In 167 cases of ad-enocarcinoma with two or more high-grade components,there were 74 cases(44.3％)of complex glands combined with mi-cropapillary components,67 cases(40.1％)of complex glands combined with solid components,8 cases(4.8％)of micropap-illary combined with solid components,and 18 cases(10.8％)of three types of components.The positive rates of pleural inva-sion and KRAS gene mutation or fusion gene(ALK/ROS1/RET)in the group of complex glands combined with solid(49.3％,28.3％)were significantly higher as compared to those in the group of complex glands combined with micropapil-lary(27.0％,8.6％).The positive rate of psammoma bodies in the group with high-grade components(24.7％)was significant-ly higher than that in those without high-grade components(3.5％,P＜0.001),and the positive rate of psammoma bodies in group of gene mutation(EGFR/KRAS)(40.4％)was higher than that in the no-gene mutation group(26.7％,P＜0.05).Conclusion The clinicopathological features of different high-grade components in stage Ⅰ lung adenocarcinoma are not identi-cal,suggesting that their invasiveness may have different biologi-cal backgrounds.Characteristic morphological observations are helpful.

Objective:To evaluate the immunogenicity and protective effect of a multicomponent recombinant protein vaccine EPRHP014 constructed independently and provide a scientific basis for developing new tuberculosis (TB) vaccine and effective prevention and control of TB.Methods:Three full-length Mycobacterium ( M.) tuberculosis protein antigens (EsxH, Rv2628, and HspX) and two epitope-predicted and optimized epitope-dominant protein antigens (nPPE18 and nPstS1) were selected, from which five protein antigens were used to construct a protein antigen composition EPRHP014, including a fusion expression multi-component protein antigen (EPRHP014f) and a multi-component mixed protein antigen (EPRHP014m) formed with the five single protein using clone, purification, and purification respectively. Multicomponent protein vaccines EPRHP014f and EPRHP014m were prepared with aluminum adjuvant, and the BCG vaccine was used as a control. ELISA detected the titer of serum-specific antibodies, the secretion of various cytokines was detected by ELISpot and Luminex, and immune protection was observed by the M.tuberculosis growth inhibition test in vitro. The results were statistically analyzed by t-test or rank sum test, and P<0.05 was considered a statistically significant difference. Results:Mice Immunized with EPRHP014m and EPRHP014f could produce highly effective IgG antibodies and their subtypes IgG1 and IgG2a, and the antibody titers were similar to those of mice immunized with BCG, with no statistical significance ( P>0.05). The number of spot-forming cells (SFC) secreting IFN-γ and IL-4 induced by EPRHP014f group was significantly higher than those by EPRHP014m group and BCG group ( P<0.05), but there was no significant difference in the number of SFC for IFN-γ and IL-4 induced between EPRHP014m group and BCG group ( P>0.05). The secretion levels of GM-CSF and IL-12p70 induced by the EPRHP014m group were higher than those of the BCG group ( P<0.05), but there was no significant difference in the levels of IL-6 and IL-10 induced between EPRHP014m group and BCG group ( P>0.05). There was no significant difference in the secretions of IL-6, IL-10, IL-12, and GM-CSF between the EPRHP014f and BCG groups ( P>0.05). EPRHP014m group, EPRHP014f group, and BCG group had obvious antibacterial effects in vitro, and the difference was insignificant ( P>0.05). Conclusion:Both EPRHP014f and EPRHP014m can induce strong humoral and cellular immune responses in mice after immunization, and have a strong ability to inhibit the growth of M. tuberculosis in vitro, indicating that the antigen composition EPRHP014 has good potential in the development and application of TB vaccine.

Objective: To examine the association between the cross-resistance to ethionamide (Eto) and isoniazid (INH) and mutations of drug resistant genes in Mycobacterium tuberculosis (MTB), so as to provide the evidence for clinical diagnosis and treatment for multidrug-resistant (MDR) tuberculosis. Methods: Totally 126 MTB clinical isolates were selected, including 88 MDR-MTB clinical isolates and 38 INH- and rifampicin (RFP)-sensitive isolates. The resistance to INH and Eto was tested in MTB clinical isolates using the drug susceptibility test, and the mutations in the spacer region of INH and Eto resistance-related katG, inhA, ethA, mshA, ndh, spacer region of oxyR-ahpC and inhA promoter were detected using PCR assay. The phenotypic resistance served as a gold standard, and the sensitivity, specificity and accuracy of gene mutation tests were calculated for detection of MTB clinical isolates cross-resistant to INH and Eto. Results: Of the 126 MTB clinical isolates, there were 37 isolates cross-resistant to INH and Eto (29.37%), 51 isolates with resistance to INH and susceptibility to Eto (40.48%), 4 isolates with susceptibility to INH and resistance to Eto (3.17%) and 34 isolates with susceptibility to INH and Eto (26.98%). Among the 41 Eto-resistant MTB clinical isolates, there were 37 isolates with resistance to INH (90.24%). There were 64 MTB clinical isolates detected with katG mutations (50.79%), 4 isolates with mutation in the spacer region of oxyR-ahpC (3.17%), 2 isolates with inhA mutations (1.59%), and these isolates were all resistant to INH. There were 11 MTB clinical isolates detected with mutation in the inhA promoter (8.73%) and one isolate with ndh mutation, and all these isolates were cross-resistant to INH and Eto. There were 23 MTB clinical isolates detected with ethA mutations (18.25%) and 40 isolates with mshA mutations (31.75%), in which Eto-susceptible and -resistant isolates were detected. The diagnostic sensitivity, specificity and accuracy of inhA promoter tests for detection of cross-resistance to INH and Eto were 29.73% (95%CI: 16.44%-47.17%), 100.00% (95%CI: 87.36%-100.00%) and 63.38% (95%CI: 51.76%-73.63%) in MTB clinical isolates. Conclusions The prevalence of INH resistance is high in Eto-resistant MTB clinical isolates. Mutation in the inhA promoter region correlates with the cross-resistance to INH and Eto in MTB clinical isolates, and detection of mutation in the inhA promoter may be feasible to detect the cross-resistance to INH and Eto in MTB clinical isolates.

OBJECTIVE To explore the role of the establishment of the trans-regional review system on rational drug use in second-grade general hospital ，and to promote the rational drug use. METHODS With the administrative support of Jiuquan Health Commission，5 second-grade general hospitals in Jiuquan Medical Association jointly established Jiuquan Rational Drug Use Review Training Center . A trans-regional review system was established to carry out cross-review of prescriptions and medical orders among 5 second-grade general hospitals. Totally 1 500 prescriptions and 900 medical records were collected from 5 second-grade general hospitals before （April to June ，2020）and after （July to September ，2020）the implementation of the project. The changes of rational drug use indicators ，the results of prescriptions and medical order review were investigated before and after the implementation of the project. RESULTS After the implementation of the project ，except for one hospital ，the proportion of drugs in other hospitals decreased to varying degrees with the highest decline rate of 22.56％ . Compared with before the implementation of the project ，reasonable rate of outpatient and emergency prescription review increased by 5.72％ averagely and the reasonable rate of medical order review increased by 10.10％（P＜0.05）. The average utilization rate of antibiotics in outpatients decreased by 14.45％，the average utilization rate of antibiotics in inpatients decreased by 7.98％，and the average use intensity of antibiotics decreased by 25.19％. CONCLUSIONS Through the establishment of trans-regional review system ，medical institutions can be forced to pay more attention to prescription review ，effectively improve the prescription review of pharmacists in medical institutions，and promote the rational use of drugs in medical institutions in the region. However ，there are still some problems ， such as incomplete system coverage ，insufficient work experience ，lagging of informatization ，uneven pharmacist level ，and insufficient assessment and supervision of administrative functional departments.