Objective: To explore the long term trend of forced vital capacity to weight index (FWI) among Chinese Han students aged 7-18 from 2000 to 2019, and to predict its changes over the next decade, so as to provide scientific evidences for targeted health interventions and school health policies. Methods: Based on the data of the five Chinese National Surveys on Students Constitution and Health conducted from 2000 to 2019, a total of 216 500, 233 565, 215 267, 214 256 and 212 632 Han students aged 7-18 were included, respectively. The long term trend of FWI among students was analyzed, and the GM (1,1) grey model was used to predict FWI changes over the next decade. Subgroup analyses were conducted by sex, age, and urban-rural residence. Results: The FWI levels of Chinese Han students aged 7-18 were (55.30±11.47)(47.43±11.92)(48.11±12.46)(48.75±12.81)(50.93±13.11)mL/kg in 2000, 2005, 2010, 2014, and 2019, respectively. The FWI of Chinese Han students showed a decreasing then increasing trend from 2000 to 2019, reaching the lowest point of approximately 47.03 mL/kg around 2006, and was projected to recover to 52.88 mL/kg by 2029. Boys had higher FWI for each year and the total level than girls from 2000 to 2019( t =72.58-304.66), and the decline between 2000 and 2005 was smaller in boys (13.1%) than in girls (15.4%). However, the gender gap gradually narrowed and was projected to reduce to 5.36 mL/kg by 2029. FWI increased with age, with the largest difference observed in 2014 between the 7-9 and 16-18 age groups (8.62 mL/kg). Before 2014, urban boys had slightly lower FWI than rural boys; the gap narrowed thereafter, and their FWI levels were expected to become similar by 2029. Urban girls generally had higher FWI than rural girls, and the urban-rural gap showed an increasing trend. By 2029, the largest difference was projected to occur in the 13-15 age group, reaching 7.74 mL/kg. Conclusions The FWI of Chinese Han students showed a trend of initial decline followed by a gradual increase from 2000 to 2019, with notable differences across sex, age, and urban-rural residence. Greater attention should be paid to the respiratory health of rural girls, and effective measures should be taken to reduce urban-rural disparities.

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4⁺ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4⁺ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Animals ; Humans ; Mice ; CD4-Positive T-Lymphocytes/pathology* ; Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Mice, Inbred C57BL ; Multiple Sclerosis ; Th1 Cells/pathology*

Objective: To investigate the influencing factors for mild cognitive impairment (MCI) among the elderly inpatients of the department of geriatrics, so as to provide the reference for early screening and prevention of MCI in the elderly population. Methods: Inpatients aged 60 years and older and admitted to the Department of Geriatrics at the First Affiliated Hospital of Xinjiang Medical University were selected as the study subjects. Demographic information, past medical history, activities of daily living (ADL), depressive symptoms were collected through questionnaire surveys. MCI was diagnosed with Montreal Cognitive Assessment in combination with medical history and physical examination. Factors affecting MCI were identified using a multivariable logistic regression model. Results: A total of 1 019 elderly patients were collected, including 472 males (46.32%) and 547 females (53.68%), and had a median age of 73.00 (interquartile range, 14.00) years. Among them, 746 patients had an educational level of junior high school or above, accounting for 73.21%, 446 patients had cerebrovascular disease, accounting for 43.77%, and 220 patients were diagnosed with MCI, with a detection rate of 21.59%. Multivariable logistic regression analysis showed that age (OR=1.354, 95%CI: 1.285-1.426), educational level (primary school, OR=0.345, 95%CI: 0.163-0.731; junior high school or above, OR=0.196, 95%CI: 0.096-0.402), ADL (moderate/severe dependence, OR=4.744, 95%CI: 2.044-11.012) and cerebrovascular disease (OR=2.335, 95%CI: 1.482-3.679) were the influencing factors for MCI among geriatric inpatients. Conclusions The MCI of the elderly inpatients of the department of geriatrics is related to age, educational level, ADL and cerebrovascular disease. Therefore, targeted health education and cognitive function training should be provided for elderly patients to prevent MCI.

Objective:To investigate the relationship between the virulence and the carbapenem resistance phenotype of Klebsiella pneumoniae from blood infection,and to identify carbapenem-resistant and hypervirulent Klebsiella pneumoniae(CR-HVKP)strains.Methods:A total of 192 Klebsiella pneumoniae strains were isolated from blood culture of patients with bloodstream infections from 2016 to 2019,of which 96 isolates were carbapenem-resistant Klebsiella pneumoniae(CRKP)and 96 were carbapenem-sensitive Klebsiella pneumoniae(CSKP).The drug susceptibility was detected by VITEK-2 automatic microbial analyzer;carbapenemase genes,virulence genes and capsule typing were detected by polymerase chain reaction;the high viscosity phenotype of strains was detected by string test,and the genome characteristics of CR-HVKP were detected by whole genome sequencing.Serum killing and biofilm formation test were used to further verify the virulence of CR-HVKP.Results:There were significant differences in drug resistance to common antibiotics,except for minocycline between CSKP and CRKP isolates(all P<0.05).92 out of 96 CRKP isolates carried carbapenemase genes,mainly blaKPC-2.The string tests were positive in 4 isolates of CRKP and 36 isolates of CSKP(P<0.05).The detection rates of virulence genes Kfu,aerobictin,iutA,ybtS,rmpA,magA,allS,and capsule antigen K1 and K2 in CSKP group were significantly higher than those in CRKP group(all P<0.05).One HVKP strain was detected in the CRKP group(CR-HVKP)and 36 HVKP was detected in the CSKP group(P<0.05).The CR-HVKP strain belonged to the MLST412,serotype K57,expressed iutA,entB,mrkD,fimH,and rmpA virulence genes,and showed strong biofilm formation and significantly increased serum resistance.Whole genome sequencing results showed that this CR-HVKP isolate carried blaSHV-145,blaTEM-1,blaCTX-M-3,fosA6,oqxA5,oqxB26,and aac(3)-Ⅱd resistance genes,accompanied by abnormalities in outer membrane protein K(OmpK)35 and OmpK36.Conclusions:The drug resistance of CRKP is significantly higher than that of CSKP,while CRKP carrying fewer virulence genes in both number and types compared to CSKP.A new MLST type of carbapenem-resistant and hypervirulent Klebsiella pneumoniae strain has been detected,which requires clinical awareness and epidemiological monitoring.

Objective:To analyze the differential genes and related signaling pathways of microglia subpopulations in Parkinson's disease (PD) -like mouse brains induced by paraquat (PQ) based on single-cell RNA sequencing, and provide clues to elucidate the mechanism of PQ-induced PD-like changes in the brain of animals.Methods:In September 2021, six male 6-week-old C57BL/6 mice were randomly divided into control group and experimental group (three mice in each group) . The mice were injected with saline, 10.0 mg/kg PQ intraperitoneally, once every three days, and 10 consecutive injections were used for modeling. After infection, the brains of mice were taken and 10×Genomics single-cell RNA sequencing was performed. Microglia subpopulations were screened based on gene expression characteristics, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The differential genes of microglia subpopulations between the experimental group and control group were further screened, and functional enrichment analysis was performed using bioinformatics tools. Mouse microglia (BV2 cells) were treated with 0, 60, 90 μmol/L PQ solution, respectively. And real-time fluorescence quantitative PCR experiments were conducted to validate the expressions of differential genes hexokinase 2 (Hk2) , ATPase H+ Transporting V0 Subunit B (Atp6v0b) and Neuregulin 1 (Nrg1) .Results:Cluster 7 and Cluster 20 were identified as microglia subpopulations based on the signature genes inositol polyphosphate-5-phosphatase d, Inpp5d (Inpp5d) and transforming growth factor beta receptor 1 (Tgfbr1) , and they reflected the microglia-activated M2 phenotype. The bioinformatics analysis showed that the characteristic genes of identified microglia subpopulations were enriched in endocytosis. In terms of molecular function, it mainly enriched in transmembrane receptor protein kinase activity and cytokine binding. The up-regulated genes of Cluster 7 were mainly enriched in lysosomal pathway, endocytosis pathway, and down-regulated genes were mainly enriched in neurodegenerative disease and other signaling pathways. The up-regulated genes of Cluster 20 were mainly enriched in signaling pathways related to PD, and down-regulated genes were mainly enriched in cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathways, neurological development, synaptic function and other signaling pathways. The results of real-time fluorescence quantitative PCR showed that the expressions of Hk2 mRNA and Atp6v0b mRNA increased and the expression of Nrg1 mRNA decreased in the 90 μmol/L PQ-treated BV2 cells compared with the 0 μmol/L, and the differences were statistically significant ( P<0.05) . Conclusion:Microglia are activated in the PQ-induced PD-like mouse model and polarized toward the M2 phenotype. And their functions are associated with lysosomal (endocytosis) , synaptic functions and the regulation of PD-related pathways.

OBJECTIVE To extract the-SH active fractions(SHF)from Bubali Cornu(water buffalo horn)and evaluate its an-tipyretic activity.METHODS SHF was extracted from Bubali Cornu by SDS-DTT,and the content of native thiols(-SH)was deter-mined by Ellman reagent method.SHF was identified based on nano LC-MS/MS technology.Evaluation of antipyretic activity of SHF was based on LPS-induced fever rat model.The levels of PGE2,IL-1β,and TNF-α in plasma as well as the levels of cAMP,PGE2,and TNF-α in the hypothalamus were measured by ELISA kits.An untargeted metabolomics approach was used to further investigate the intervention of SHF on plasma metabolites in febrile rats.RESULTS SDS-DTT could effectively extract SHF from Bubali Cornu,in which the main components were type Ⅰ,type Ⅱ keratins and keratin-associated proteins,which were rich in Cys,and the ratio of-SH to protein in SHF was increased about 20 times more than that of traditional decoction.SHF could significantly decrease(P＜0.01)the body temperature which lasted for 4.5 hours.SHF could also significantly decrease the levels of PGE2,IL-1β,TNF-α and cAMP in plasma and hypothalamic.A total of 137 potentially differential metabolites were identified from plasma samples of the control and model groups,of which 31 metabolites could be dialed back after SHF administration,including lysophosphatidic acid,phosphatidyli-nositol,phosphatidic acid,triglycerides,phosphatidylcholine and so on,which were mainly involved in the glycerophospholipid meta-bolic pathway.CONCLUSION SHF has precise antipyretic effect,and the dosage of 1/10 of the aqueous extract can show its com-parable antipyretic effect,which provides the direction and basis for the basic research on the antipyretic efficacy of Bubali Cornu.

Objective To investigate the effect of malignant cerebellar hemorrhage on 3-month prognosis of small spontaneous cerebellar hemorrhage.Methods Clinical data of 380 consecutive patients with spontaneous cerebellar hemorrhage admitted in Emergency Department of the Affil-iated Hospital of Guizhou Medical University,Neurosurgery Department of Jinyang Hospital Af-filiated to Guizhou Medical University,and Neurosurgery Department of the Second Affiliated Hospital of Guizhou Medical University from April 2014 to March 2023 were collected and retro-spectively analyzed,and finally,70 patients who met the requirements of small amount of sponta-neous cerebellar hemorrhage were enrolled in this study.They were assigned into benign cerebel-lar hemorrhage group(43 cases)and malignant cerebellar hemorrhage group(27 cases).Accord-ing to their clinical outcomes in 3 months after onset,they were divided into a good prognosis group(51 cases)and a poor prognosis group(19 cases).General clinical data,imaging data,com-plications,inflammatory indicators and prognosis were collected.After collinear diagnosis was used to exclude factors with collinear influence,the independent correlation between good progno-sis and poor prognosis was analyzed by binary logistic regression model.Finally,ROC curve was plotted to analyze the significant data.Results The maximum diameter of hematoma was signifi-cantly larger in the malignant cerebellar hemorrhage group than the benign group(P=0.021).The patients of the poor prognosis group had larger proportion of malignant cerebellar hemor-rhage,and higher neutrophil percentage,WBC count and NLR than those of the good prognosis group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that malignant cere-bellar hemorrhage was an independent predictor of poor prognosis in 3 months(OR=6.218,95％CI:1.140-17.623,P=0.013).The sensitivity,specificity,positive predictive value,negative pre-dictive value and Youden index of malignant cerebellar hemorrhage in predicting the 3-month prognosis of patients were 63.2％,70.6％,44.4％,83.7％and 0.338,respectively,and the AUC value was 0.669.Conclusion Malignant cerebellar hemorrhage is an independent predictor of 3-month prognosis in patients with small spontaneous cerebellar hemorrhage.The patients with malignant cerebellar hemorrhage have poor prognosis than those with benign cerebellar hemorrhage.

Objective:To analyze the differential genes and related signaling pathways of microglia subpopulations in Parkinson's disease (PD) -like mouse brains induced by paraquat (PQ) based on single-cell RNA sequencing, and provide clues to elucidate the mechanism of PQ-induced PD-like changes in the brain of animals.Methods:In September 2021, six male 6-week-old C57BL/6 mice were randomly divided into control group and experimental group (three mice in each group) . The mice were injected with saline, 10.0 mg/kg PQ intraperitoneally, once every three days, and 10 consecutive injections were used for modeling. After infection, the brains of mice were taken and 10×Genomics single-cell RNA sequencing was performed. Microglia subpopulations were screened based on gene expression characteristics, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The differential genes of microglia subpopulations between the experimental group and control group were further screened, and functional enrichment analysis was performed using bioinformatics tools. Mouse microglia (BV2 cells) were treated with 0, 60, 90 μmol/L PQ solution, respectively. And real-time fluorescence quantitative PCR experiments were conducted to validate the expressions of differential genes hexokinase 2 (Hk2) , ATPase H+ Transporting V0 Subunit B (Atp6v0b) and Neuregulin 1 (Nrg1) .Results:Cluster 7 and Cluster 20 were identified as microglia subpopulations based on the signature genes inositol polyphosphate-5-phosphatase d, Inpp5d (Inpp5d) and transforming growth factor beta receptor 1 (Tgfbr1) , and they reflected the microglia-activated M2 phenotype. The bioinformatics analysis showed that the characteristic genes of identified microglia subpopulations were enriched in endocytosis. In terms of molecular function, it mainly enriched in transmembrane receptor protein kinase activity and cytokine binding. The up-regulated genes of Cluster 7 were mainly enriched in lysosomal pathway, endocytosis pathway, and down-regulated genes were mainly enriched in neurodegenerative disease and other signaling pathways. The up-regulated genes of Cluster 20 were mainly enriched in signaling pathways related to PD, and down-regulated genes were mainly enriched in cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathways, neurological development, synaptic function and other signaling pathways. The results of real-time fluorescence quantitative PCR showed that the expressions of Hk2 mRNA and Atp6v0b mRNA increased and the expression of Nrg1 mRNA decreased in the 90 μmol/L PQ-treated BV2 cells compared with the 0 μmol/L, and the differences were statistically significant ( P<0.05) . Conclusion:Microglia are activated in the PQ-induced PD-like mouse model and polarized toward the M2 phenotype. And their functions are associated with lysosomal (endocytosis) , synaptic functions and the regulation of PD-related pathways.

Objective:To analyze the epidemiological characteristics of respiratory virus infections in Sichuan from 2017 to 2023, and investigate the changes in detection rates of various viruses in different periods and age groups.Methods:The study included 41 516 patients with acute respiratory infections. Clinical laboratory results of these patients were retrospectively collected to calculate the detection rates of various viruses. The epidemiological characteristics of respiratory virus infections before, during, and after the COVID-19 pandemic, the prevalence of mixed infections, and the detection rates in different seasons and age groups were analyzed.Results:The overall detection rate of respiratory viruses was 23.35% (9 696/41 516), with influenza A virus (8.47%, 3 515/41 516), rhinovirus (7.13%, 2 961/41 516), and influenza B virus (2.04%, 846/41 516) being the most prevalent. The highest detection rate was observed in children aged 0-14 years (48.62%, 1 429/2 939), while the detection rates in young, middle-aged, and elderly individuals were similar [21.00% (1 482/7 057), 22.06% (3 828/17 350), 20.33% (2 685/13 205)]. The detection rate of influenza A virus dropped to 1.35% (253/18 717) during the COVID-19 pandemic, and rebounded to 13.05% (1 560/11 953) after the pandemic. A similar pattern was observed in other viruses such as human metapneumovirus, influenza B virus, coronavirus, and respiratory syncytial virus, with significant reductions during the COVID-19 pandemic and subsequent increases that even exceeded pre-pandemic levels. The detection rates of adenovirus, bocavirus, and rhinovirus gradually decreased over time, while the prevalence of parainfluenza virus remained stable, indicating a less significant impact of COVID-19 on these viruses. Higher detection rates were observed in autumn (28.90%, 2 324/8 041) and winter (26.52%, 4 093/15 433) as compared to that in spring (17.61%, 1 848/10 494) and summer (18.96%, 1 431/7 548), suggesting significant seasonal impacts on virus detection rates ( P<0.001). This study identified 8 666 cases of single-virus infections, 948 double infections, 77 triple infections, and five quadruple infections. Co-infection of bocavirus and rhinovirus was the most common type of double infections (17.41%, 165/948), and 59.60% (565/948) of double infections involved rhinovirus. Conclusions:The overall detection rate of respiratory viruses is higher in autumn and winter than in spring and summer. The prevalence of some respiratory viruses such as influenza viruses decreases during the COVID-19 pandemic. People of different ages can develop multiple infections with rhinovirus being the most common in double infections.

BACKGROUND: Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC stimulus are still not clear. Quantitative proteomic analyses of plasma proteins following RIC application have been conducted in preclinical and clinical studies but exhibit high heterogeneity in results due to wide variations in experimental setups and sampling procedures. Hence, this study aimed to explore the immediate effects of RIC on plasma proteome in healthy young adults to exclude confounding factors of disease entity, such as medications and gender. METHODS: Young healthy male participants were enrolled after a systematic physical examination and 6-month lifestyle observation. Individual RIC sessions included five cycles of alternative ischemia and reperfusion, each lasting for 5 min in bilateral forearms. Blood samples were collected at baseline, 5 min after RIC, and 2 h after RIC, and then samples were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry method. RESULTS: Proteins related to lipid metabolism (e.g., Apolipoprotein F), coagulation factors (hepatocyte growth factor activator preproprotein), members of complement cascades (mannan-binding lectin serine protease 1 isoform 2 precursor), and inflammatory responses (carboxypeptidase N catalytic chain precursor) were differentially altered at their serum levels following the RIC intervention. The most enriched pathways were protein glycosylation and complement/coagulation cascades. CONCLUSIONS One-time RIC stimulus may induce instant cellular responses like anti-inflammation, coagulation, and fibrinolysis balancing, and lipid metabolism regulation which are protective in different perspectives. Protective effects of single RIC in hyperacute and acute phases may be exploited in clinical emergency settings due to apparently beneficial alterations in plasma proteome profile. Furthermore, the beneficial effects of long-term (repeated) RIC interventions in preventing chronic cardiovascular diseases among general populations can also be expected based on our study findings.
Young Adult ; Humans ; Male ; Proteome ; Cardiovascular Diseases ; Proteomics ; Ischemia ; Blood Coagulation