ObjectiveTo investigate the status and influencing factors of latent tuberculosis infection (LTBI) among close contacts of patients with bacteriologically confirmed pulmonary tuberculosis in Jing’an District, Shanghai, and to provide scientific evidence for the development of tuberculosis infection testing and preventive intervention strategies for close contacts of bacteriologically positive patients. MethodsFrom October 2022 to October 2023, patients with bacteriological confirmed pulmonary tuberculosis registered in Jing’an District, Shanghai, and their close contacts were enrolled as the research subjects. The close contacts were screened for tuberculosis infection using the interferon-γ release assay (IGRA). The chi-square test and binary logistic regression model were used to analyze factors influencing LTBI. ResultsA total of 112 close contacts were included, of whom 30 (26.79%) were male and 82 (73.21%) were female. The age ranged from 1 to 86 years, with a median (25th, 75th percentiles) of 47.50 (32.25, 61.00) years. The infection rate of LTBI was 21.43% (24/112), and the incidence of active pulmonary tuberculosis was 2.68% (3/112). Univariate analyses showed that a positive sputum smear of the index case, being a direct relative of the index case, co-living, and not wearing a mask were significantly associated with LTBI (all P<0.05). Multivariate logistic regression analyses showed that the risk of latent infection in close contacts of the index case with a positive sputum smear was 6.50 times higher than in those with a negative sputum smear (95%CI: 1.82‒23.25, P=0.004). ConclusionThe infection rate of LTBI in close contacts of patients with bacteriologically confirmed pulmonary tuberculosis in Jing’an District, Shanghai, is relatively high, and close contacts of sputum smear-positive patients face an even higher risk of infection. Therefore, tuberculosis infection screening and follow-up management should be strengthened for this population.

Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.

ObjectiveTo analyze the reported incidence rate of pulmonary tuberculosis and diagnosis and treatment of pulmonary tuberculosis patients in Jing’an District, Shanghai from 2018 to 2023, and to provide a reference basis for the prevention and treatment of pulmonary tuberculosis. MethodsMedical records, including demographic information, diagnosis and treatment information, laboratory testing results, treatment outcomes, patient prognoses, and etc., of all the patients registered for first-time management, with the disease type of pulmonary tuberculosis in Jing’an District from January 1, 2018 to December 31, 2023 were extracted from the Tuberculosis Management Information System of China’s Disease Control and Prevention Information System.The reported incidence rate of pulmonary tuberculosis from 2018 to 2023 was analyzed. Additionally, the delay rate for medical consultation, diagnostic delay rate, prevalence of pulmonary cavity, rate of sputum smear-positive, sputum conversion rate of smear-positive patients after 2 months, proportion of deaths attributable to pulmonary tuberculosis or other causes, and the proportion of patients with treatment duration >1 year in 2018‒2019, 2020‒2022, and 2023 were compared, respectively. ResultsA total of 1 378 pulmonary tuberculosis patients were registered for management in Jing’an District in 2018‒2023, with a reported incidence rate of 25.97/100 000, 25.72/100 000, 23.93/100 000, 22.36/100 000, 18.18/100 000, and 22.32/100 000, respectively. Meanwhile, the overall reported incidence rates in 2018‒2019, 2020‒2022, and 2023 were 25.84/100 000, 21.53/100 000, and 22.32/100 000, respectively. The median age of the patients was 56 (33, 67) years, with a male-to-female ratio of 1.94∶1. The patients with a household registration of Shanghai accounted for 70.75%, among whom those aged between 61‒<71 years were the majority. Whereas, those aged between 31‒<41 years accounted for a higher proportion in the long-term resident population. The median delay times of patient’s medical consultation, diagnosis, and case-finding were 25 (19, 33) days, 29 (21, 43) days, and 41 (32, 66) days, respectively. The delay rate for medical consultation was higher in 2020‒2022 (47.99%) and 2023 (46.89%), but lower in 2018‒2019 (31.02%). In 2018‒2019, 2020‒2022, and 2023, the diagnostic delay rate was 12.41% (68/548), 13.53% (84/621), and 16.75% (35/209), respectively. Besides, during the same time the delay rate in case-finding was 19.53%, 27.05% and 34.45%, respectively, all exhibited an increasing trend. Furthermore, the rate of patients with pulmonary cavity was 16.06%, 14.98%, and 11.00%, respectively, showing a decreasing trend. Furthermore, the rate of sputum smear-positive was 27.19%, 33.33% and 32.54%, while the sputum conversion rate of smear-positive patients after 2 months was 81.21%, 85.02% and 89.71%. The mortality rates due to tuberculosis and other causes were 3.10%, 5.64%, and 3.83%, respectively. The proportion of patients with a treatment duration of ≥365 days was 44.27% in 2018‒2019, 39.93% in 2020‒2022 and 26.60% in 2023. ConclusionThe overall reported incidence rate of pulmonary tuberculosis in Jing’an District showed a decline trend from 2018‒2022, with a slight rebound in 2023. Targeted interventions should be prioritized for the elderly with local household registration and young permanent residents without Shanghai household registration.

Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.

AIM:To explore the impact of chronic stress on postoperative cognitive dysfunction in rats and to elucidate the mechanistic link to histone deacetylase 2(HDAC2).METHODS:A repeated social defeat stress model and a prolonged isoflurane anesthesia model were established in mice.The rats were randomly assigned to four groups:control(Ctrl)group,isoflurane anesthesia(Iso)group,chronic social defeat stress(RSDS)group,and chronic social de-feat stress combined with isoflurane anesthesia(RSDS+Iso)group.Anxiety-like behaviors were evaluated using the social avoidance test and the novelty-suppressed feeding test.Cognitive function was assessed through the novel object recogni-tion test and the Morris water maze.Plasma corticosterone levels were measured via enzyme-linked immunosorbent assay(ELISA).Primary hippocampal neurons were isolated from fetal mouse hippocampi and classified into four groups:con-trol group,chronic stress combined with prolonged isoflurane anesthesia(Cort+Iso)group,CAY-10683 intervention(CAY),and CAY-10683 treatment(CAY+Cort+Iso)group.Cell viability was determined using CCK-8 assay,and pro-tein expression levels of brain-derived neurotrophic factor(BDNF)and HDAC2 were analyzed by Western blot.RE-SULTS:The RSDS mouse model was successfully established,with ELISA results indicating a significant increase in plasma corticosterone levels in mice subjected to chronic stress combined with prolonged isoflurane anesthesia.Behavioral assessments and Western blot analyses revealed that mice exposed to prolonged isoflurane anesthesia following chronic stress showed marked declines in cognitive function and hippocampal BDNF protein expression levels.Additionally,chronic stress significantly elevated HDAC2 protein expression in the hippocampi of mice undergoing prolonged isoflurane anesthesia.Treatment with an HDAC2 inhibitor reduced HDAC2 protein expression in primary hippocampal neurons sub-jected to chronic stress combined with prolonged isoflurane anesthesia,concurrently increasing BDNF protein expression levels.CONCLUSION:Chronic stress significantly worsens postoperative cognitive dysfunction induced by prolonged isoflurane anesthesia,associated with increased HDAC2 protein expression in the hippocampus.Inhibition of HDAC2 ef-fectively counteracts the reduction in BDNF,a protein crucial for cognitive function,caused by the combination of chronic stress and prolonged isoflurane anesthesia.

AIM:To explore the impact of chronic stress on postoperative cognitive dysfunction in rats and to elucidate the mechanistic link to histone deacetylase 2(HDAC2).METHODS:A repeated social defeat stress model and a prolonged isoflurane anesthesia model were established in mice.The rats were randomly assigned to four groups:control(Ctrl)group,isoflurane anesthesia(Iso)group,chronic social defeat stress(RSDS)group,and chronic social de-feat stress combined with isoflurane anesthesia(RSDS+Iso)group.Anxiety-like behaviors were evaluated using the social avoidance test and the novelty-suppressed feeding test.Cognitive function was assessed through the novel object recogni-tion test and the Morris water maze.Plasma corticosterone levels were measured via enzyme-linked immunosorbent assay(ELISA).Primary hippocampal neurons were isolated from fetal mouse hippocampi and classified into four groups:con-trol group,chronic stress combined with prolonged isoflurane anesthesia(Cort+Iso)group,CAY-10683 intervention(CAY),and CAY-10683 treatment(CAY+Cort+Iso)group.Cell viability was determined using CCK-8 assay,and pro-tein expression levels of brain-derived neurotrophic factor(BDNF)and HDAC2 were analyzed by Western blot.RE-SULTS:The RSDS mouse model was successfully established,with ELISA results indicating a significant increase in plasma corticosterone levels in mice subjected to chronic stress combined with prolonged isoflurane anesthesia.Behavioral assessments and Western blot analyses revealed that mice exposed to prolonged isoflurane anesthesia following chronic stress showed marked declines in cognitive function and hippocampal BDNF protein expression levels.Additionally,chronic stress significantly elevated HDAC2 protein expression in the hippocampi of mice undergoing prolonged isoflurane anesthesia.Treatment with an HDAC2 inhibitor reduced HDAC2 protein expression in primary hippocampal neurons sub-jected to chronic stress combined with prolonged isoflurane anesthesia,concurrently increasing BDNF protein expression levels.CONCLUSION:Chronic stress significantly worsens postoperative cognitive dysfunction induced by prolonged isoflurane anesthesia,associated with increased HDAC2 protein expression in the hippocampus.Inhibition of HDAC2 ef-fectively counteracts the reduction in BDNF,a protein crucial for cognitive function,caused by the combination of chronic stress and prolonged isoflurane anesthesia.

Objective To analyze the effect of circLRP6 on high glucose-induced renal tubular epithelial cell injury via miR-31-5p/high mobility group protein A1(HMGA1)axis regulation.Methods Human renal tubular epithelial HK-2 cells were cultured in vitro and divided into eight groups:control,high glucose,high glucose+si-NC,high glucose+si-circLRP6,high glucose+si-circLRP6+miR-NC,high glucose+si-circLRP6+miR-31-5p inhibitor,high glucose+si-circLRP6+miR-31-5p inhibitor+si-NC,and high glucose+si-circ-LRP6+ miR-31-5p inhibitor+si-HMGA1.The circLRP6,miR-31-5p,and HMGA1 mRNA levels were determined using real-time quantitative PCR.Cell supernatant IL-6 and tumor necrosis factor-α(TNF-α)levels,lactate dehydrogenase(LDH)activity,and malondialdehyde(MDA)content were also determined.Furthermore,flow cytometry was used to observe cell apoptosis.HMGA1,Bax,and Bcl-2 protein expression was detected by Western blotting.Finally,dual luciferase assay was used to report the targeting relationship of miR-31-5p with circLRP6 and HMGA1.Results Compared with the high glucose group,the HK-2 cell proliferation inhibition rate;cell superserum IL-6,TNF-α,LDH,and MDA levels;apoptosis rate;and Bax protein expression in the high glucose+si-circLRP6 group decreased significantly,whereas Bcl-2 protein expression increased significantly(all P＜0.05).Consequently,miR-31-5p downregulation possibly weakened the protective effect of si-circLRP6 on high glucose-induced renal tubular epithelial cell injury.HMGA1 expression inhibition reversed the effect of the si-circLRP6+miR-31-5p inhibitor on high glucose-induced renal tubular epithelial cell injury.Finally,miR-31-5p exhibited a targeting relationship with circLRP6 and HMGA1.Conclusion Si-circLRP6 protects high glucose-induced renal tubular epithelial cell injury via miR-31-5p upregulation and HMGA1 expression inhibition.

OBJECTIVE To establish the characteristic chromatogram of the volatile oil in the standard decoction of Qingshang juantong decoction， and preliminarily infer the main active components of volatile oil that affect the clinical therapeutic effect. METHODS The volatile oil in the standard decoction of Qingshang juantong decoction was extracted by steam distillation. The ultra-high performance liquid chromatography （UPLC） characteristic chromatograms of 15 batches of samples were established by the Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition）， and the similarity evaluation was carried out. The volatile oil of standard decoction was identified by UPLC coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS）. Then the volatile oil components were analyzed by GC-MS. RESULTS The similarities of UPLC characteristic chromatograms for volatile oil of 15 batches of Qingshang juantong decoction were between 0.949 and 0.997. A total of 12 common peaks were obtained. According to the UPLC-Q-TOF/MS， the main components were methyl eugenol， E-ligustilide， E-butylidenephthalide and so on. A total of 23 components were identified by GC-MS， which were mainly 3，4，5-trimethoxy- methylbenzene， patchouli alcohol， Z-ligustilide and so on. CONCLUSIONS The characteristic chromatograms of the volatile oil in the standard decoction of Qingshang juantong decoction is established， and it is inferred that methyl eugenol， ligustilide， E- butylidenephthalide， patchouli alcohol， 3，4，5-trimethoxy-methylbenzene might be the main active components affecting the clinical therapeutic effect of the volatile oil of Qingshang juantong decoction.

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with Teebi hypertelorism syndrome 1 (TBHS1). METHODS: A child with TBHS1 who was admitted to the Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine on July 13, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 13-year-old male, had manifested delayed growth and development. WES results revealed that he has harbored a heterozygous c.1244A>G variant of the SPECC1L gene, which was verified to be de novo in origin. The variant has not been included in the HGMD and gnomAD databases. As predicted by online software including PolyPhen-2, SIFT, and Mutation Taster, the variant may affect the function of protein domain. And PyMOL software has predicted that the structural stability of SPECC1L protein (p.Gln415Arg) might be reduced. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PM6+PM1+PP4+PM2_Supporting+PP3). CONCLUSION The heterozygous c.1244A>G variant of the SPECC1L gene probably underlay the TBHS1 in this child. Above finding has expanded the genotypic and phenotypic spectrum of the SPECC1L gene and provided a basis for the clinical diagnosis of this child.
Adolescent ; Humans ; Male ; China ; Computational Biology ; Genomics ; Genotype ; Mutation

Objective:To investigate the bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China.Methods:The clinical bacterial strains isolated from blood culture were collected during January 2020 to December 2020 in member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS). Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute(CLSI, USA). WHONET 5.6 was used to analyze data.Results:During the study period, 10 043 bacterial strains were collected from 54 hospitals, of which 2 664 (26.5%) were Gram-positive bacteria and 7 379 (73.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (38.6%), Klebsiella pneumoniae (18.4%), Staphylococcus aureus (9.9%), coagulase-negative Staphylococci (7.5%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.3%), Enterobacter cloacae (2.8%), Enterococcus faecalis (2.6%), Acinetobacter baumannii (2.4%) and Klebsiella spp (1.8%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 27.6% and 74.4%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci were detected. More than 95% of Staphylococcus aureus were sensitive to rifampicin and SMZco. No vancomycin-resistant Enterococci strains were detected. Extended spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 48.4%, 23.6% and 36.1%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.3% and 16.1%, respectively; 9.6% of carbapenem-resistant Klebsiella pneumoniae strains were resistant to ceftazidime/avibactam combination. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii. The prevalence rate of carbapenem-resistance of Pseudomonas aeruginosa was 23.2%. Conclusions:The surveillance results in 2020 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen, and ESBL-producing strains declined while carbapenem-resistant Klebsiella pneumoniae kept on high level. The proportion and the prevalence of carbapenem-resistant Pseudomonas aeruginosa were on the rise slowly. On the other side, the MRSA incidence got lower in China, while the overall prevalence of vancomycin-resistant Enterococci was low.