OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

AIM To investigate the effects of stir-frying,processing with butter and carbonizing by stir-frying on oil components in Gleditsiae sinensis Fructus and Gleditsiae Fructus Abnormalis.METHODS The volatile oils and fatty oils were extracted by steam distillation method and Soxhlet extraction method,respectively,after which the extraction rates were determined.GC-MS was applied to analyzing the kinds and relative contents of oil components,after which cluster analysis was performed.RESULTS After the processing,the two medicinal materials demonstrated increased extraction rates of fatty oils and decreased extraction rates of volatile oils(except for processing with butter),the extraction rates of oil components in Gleditsiae sinensis Fructus were higher than those in Gleditsiae Fructus Abnormalis,and the reduced relative contents of toxic olefin benzene components were observable.CONCLUSION The kinds and relative contents of oil components in Gleditsiae sinensis Fructus and Gleditsiae Fructus Abnormalis exist obvious differences,the former displays better medicinal quality,whose processing mechanism in alleviating dryness and strength may contribute to the reduction of relative contents of toxic olefin benzene components.

Aim To investigate the protective effect of fisetin on testis and sperm of rats with oligoasthenosper-mia and to explore its mechanism.Methods The rat model of oligoasthenospermia was established.The rats were randomly divided into the blank group,model group,low-,medium-,and high-dose fisetin treat-ment groups,and LKB1 agonist group,with 10 rats in each group.ELISA was used to detect the levels of FSH,LH,T,E2 and PRL.Flow cytometry was used to detect sperm cell apoptosis.HE staining was used to detect testicular tissue damage.Transmission electron microscopy was used to detect the ultrastructure of sperm cells.qRT-PCR and Western blot were used to detect the mRNA and protein expression of LKB1,AMPK,mTOR,and p70S6K.Results Compared with the blank group,the levels of FSH,LH,PRL,T and other hormones in the model group and LKB1 ago-nist group were significantly reduced,and sperm cell apoptosis and testicular injury were severe.The ex-pressions of LKB1 and p-AMPK/AMPK were signifi-cantly up-regulated,while the expressions of mTOR and p-p70S6K/p70S6K were significantly down-regula-ted(P＜0.05).Compared with the model group,af-ter different doses of fisetin treatment,the number of apoptotic sperm cells was significantly reduced,the levels of FSH,LH,PRL,T and other hormones markedly increased,the expression of LKB1 and p-AMPK/AMPK was significantly down-regulated,and the expression of mTOR and p-p70S6K/p70S6K was evidently up-regulated(P＜0.05).Conclusion Fi-setin is effective in the treatment of oligoasthenospermia rats,which may be related to LKB1-AMPK-mTOR-p70S6K signaling pathway.

For the past 30 years,percutaneous balloon mitral valve dilatation has been performed under the guidance of X-rays and bedside ultrasound.However,there are still some cases of mitral valve stenosis in the large atrium where balloon dilation failed.Intraperitoneal ultrasound-guided percutaneous balloon mitral valve plasty is accurate and feasible,which can reduce the occurrence of complications and improve the success rate of such elderly complex cases.Two patients with severe mitral stenosis underwent percutaneous balloon mitral valve plasty guided by intracardiac ultrasound.The operations were successful without any complications,which can provide reference for clinical treatment of mitral stenosis.

BACKGROUND: Human interleukin (IL)-37 is a constituent of the IL-1 family with potent anti-inflammatory and immunosuppressive attributes. It has been demonstrated extensive beneficial effects on various diseases; however, its role in the pathogenesis of diabetic cardiomyopathy (DCM) remains unclear. METHODS: In vivo, DCM mouse model was established with streptozotocin injection and a high-fat diet in WT and cardiac fibroblasts (CFs) specific hIL-37b overexpression mice (IL-37-Tg). In vitro, primary mouse CFs were isolated from the hearts of adult mice and cultured with high levels of glucose and palmitic acid. Cardiac function of the mice was assessed using echocardiography. Masson staining, immunofluorescence, western blot and RT-PCR assays were employed to evaluate the expression of cardiac fibrosis and SOCS3-JAK2-STAT3 signaling pathway-related proteins. RESULTS: In this study, we found that CFs specific IL-37-Tg significantly ameliorated cardiac dysfunction and reduced collagen production by inhibiting the JAK2-STAT3 axis, as evidenced by the decreased levels of p-JAK2 and p-STAT3 in the heart of CFs specific IL-37-Tg DCM mice. The beneficial effects of IL-37 were consistently observed in CFs treated with high glucose (HG) and palmitic acid (PA). Moreover, we also discovered that the presence of IL-37 increased the expression of SOCS3, a crucial regulator of JAK/STAT signaling, in DCM mice and HG and PA-treated CFs. Finally, the anti-fibrotic action of IL-37 in HG and PA-treated CFs was abolished when either SOCS3 was genetically knocked down or JAK2/STAT3 was pharmacologically activated. CONCLUSIONS Our findings indicate that IL-37 exerts its antifibrotic effect by promoting SOCS3-mediated JAK2-STAT3 inactivation and may be considered as a potential therapeutic agent for DCM.

The plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) are native species unique to the Qinghai-Tibetan Plateau with successful adaptation to the hypoxic environment. In this study, the number of red blood cells, hemoglobin concentration, mean hematocrit and mean volume of red blood cells were measured in plateau zokors and plateau pikas at different altitudes. Hemoglobin subtypes of two plateau animals were identified by mass spectrometry sequencing. The forward selection sites in two animals' hemoglobin subunits were analyzed by PAML4.8 program. Homologous modeling was used to analyze the effect of forward selection sites on the affinity of hemoglobin to oxygen. The adapting strategies of plateau zokors and plateau pikas to hypoxia at different altitudes were analyzed through comparing blood parameters between the two species. The results indicated that, with increasing altitudes, plateau zokors responded to hypoxia by increasing red blood cell count and decreasing red blood cell volume, while plateau pikas took the opposite strategies to plateau zokors. In erythrocytes of plateau pikas, both adult α₂β₂ and fetal α₂ε₂ hemoglobins were identified, while erythrocytes of plateau zokors only had adult α₂β₂ hemoglobin, however the affinities and the allosteric effects of the hemoglobin of plateau zokors were significantly higher than those of plateau pikas. Mechanistically, in the α and β subunits of hemoglobin of plateau zokors and pikas, the numbers and the sites of the positively selected amino acids as well as the side chain groups polarities and orientations of the amino acids differed significantly, which may result in the difference of the affinities to oxygen of hemoglobin between plateau zokors and pikas. In conclusion, the adaptive mechanisms to respond to hypoxia in blood properties of plateau zokors and plateau pikas are species-specific.
Animals ; Altitude ; Amino Acids ; Hemoglobins ; Hypoxia ; Lagomorpha

Objective: To investigate the characteristics of duodenal bulbar microbiota in children with duodenal ulcer and Helicobacter pylori (Hp) infection. Methods: This prospective cohort study enrolled 23 children with duodenal ulcers diagnosed by gastroscopy who were admitted to the Children's Hospital of Zhejiang University School of Medicine due to abdominal pain, abdominal distension, and vomiting from January 2018 to August 2018. They were divided into Hp-positive and Hp-negative groups according to the presence or absence of Hp infection. Duodenal bulbar mucosa was sampled to detect the bacterial DNA by high-throughput sequencing. The statistical difference in α diversity and β diversity, and the relative abundance in taxonomic level between the two groups were compared. Microbial functions were predicted using the software PICRUSt. T-test, Rank sum test or χ² test were used for comparison between the two groups. Results: A total of 23 children diagnosed with duodenal ulcer were enrolled in this study, including 15 cases with Hp infection ((11.2±3.3) years of age, 11 males and 4 females) and 8 cases without Hp infection ((10.1±4.4) years of age, 6 males and 2 females). Compared with Hp-negative group, the Hp-positive group had higher Helicobacter abundance (0.551% (0.258%, 5.368%) vs. 0.143% (0.039%, 0.762%), Z=2.00, P=0.045) and lower abundance of Fusobacterium, Streptococcus and unclassified- Comamonadaceae (0.010% (0.001%, 0.031%) vs. 0.049% (0.011%, 0.310%), Z=-2.24, P=0.025; 0.031% (0.015%, 0.092%) vs. 0.118% (0.046%, 0.410%), Z=-2.10, P=0.036; 0.046% (0.036%, 0.062%) vs. 0.110% (0.045%, 0.176%), Z=-2.01, P=0.045). Linear discriminant analysis (LDA) effect sized showed that at the genus level, only Helicobacter was significantly enriched in Hp-positive group (LDA=4.89, P=0.045), while Streptococcus and Fusobacterium significantly enriched in Hp-negative group (LDA=3.28, 3.11;P=0.036,0.025, respectively). PICRUSt microbial function prediction showed that the expression of oxidative phosphorylation and disease-related pathways (pathways in cancer, renal cell carcinoma, amoebiasis, type 1 diabetes mellitus) in Hp-positive group were significantly higher than that in Hp-negative group (all P<0.05), while the expression of pathways such as energy metabolism and phosphotransferase system pathways were significantly lower than that in Hp-negative group (all P<0.05). Conclusion: In children with Hp-infected duodenal ulcers, the mucosal microbiota of the duodenal bulb is altered, characterized by an increased abundance of Helicobacter and a decreased abundance of Clostridium and Streptococcus, and possibly alters the biological function of the commensal microbiota through specific metabolic pathways.
Male ; Female ; Humans ; Child ; Duodenal Ulcer/diagnosis* ; Helicobacter Infections/complications* ; Helicobacter pylori/genetics* ; Prospective Studies ; Microbiota

Reduced protein S activity is one of the high-risk factors for venous thromboembolism.Hereditary protein S deficiency is an autosomal dominant disorder caused by mutations in the PROS1 gene.We reported a female patient with a mutation of c.292 G>T in exon 3 of the PROS1 gene,which was identified by sequencing.The genealogical analysis revealed that the mutation probably originated from the patient's mother.After searching against the PROS1 gene mutation database and the relevant literature,we confirmed that this mutation was reported for the first time internationally.
Humans ; Female ; Protein S/genetics* ; Protein S Deficiency/genetics* ; Pedigree ; Mutation

OBJECTIVE: To assess the effect and safety of Reyanning Mixture (RYN) in treating asymptomatic or mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. METHODS: This is a prospective, open-label, randomized controlled trial. Patients aged 1-17 years and diagnosed with asymptomatic or mild coronavirus disease-2019 (COVID-19) were assigned to an intervention group (RYN plus standard care) and a control group (standard care) according to a randomization list. The primary outcomes were SARS-CoV-2 negative conversion time. Secondary outcomes included negative conversion rate on days 3 and 7, hospital length of stay, symptom relief rate, new-onset symptoms of asymptomatic infected patients, and progressive disease rate. The cycle threshold (Ct) values of ORF1ab or N genes were also tested. RESULTS: A total of 214 patients in the intervention group and 217 in the control group were analyzed. The SARS-CoV-2 negative conversion time was significantly shortened in the intervention group [5 days (interquartile range (IQR): 5-6) vs. 7 days (IQR: 6-7), P<0.01]. By days 3 and 7, the negative conversion rates were significantly higher in the intervention group (day 3: 32.7% vs. 21.2%, P=0.007; day 7: 75.2% vs. 60.8%, P=0.001). Ct values significantly increase on day 2 [ORF1ab gene: 35.62 (IQR: 29.17-45.00) vs. 34.22 (IQR: 28.41-39.41), P=0.03; N gene: 34.97 (IQR: 28.50-45.00) vs. 33.51 (IQR: 27.70-38.25), P=0.024] and day 3 [ORF1ab gene: 38.00 (IQR: 32.72-45.00) vs. 35.81 (IQR: 29.96-45.00), P=0.003; N gene: 37.16 (IQR: 32.01-45.00) vs. 35.26 (IQR: 29.09-45.00), P=0.01]. No significant difference was found in hospital length of stay between the two groups (P>0.05). Symptoms of cough were significantly improved (82.2% vs. 70.0%, P=0.02) and wheezing was significantly reduced (0.7% vs. 12.9%, P<0.01) in the intervention group compared with the control group. During the trial, no disease progression or serious adverse events were reported. CONCLUSION Adding RYN to standard care may be a safe and effective treatment for children with asymptomatic and mild SARS-CoV-2 infection. (Registration No. ChiCTR2200060292).