Objective: To analyze the impact of persistent obesity on their lung function, so as to offer insights for implementing intervention measures to increase lung function in obese school age children. Methods: A total of 335 children from the Sheyang Mini Birth Cohort established in 2009 in Yancheng City, Jiangsu Province, who participated in the follow up at the ages of 7 years (2016) and 10 years (2019), were selected as the study participants. Physical measurements including height, weight, and lung function were recorded. According to the World Health Organization standard, that is, gender and age specific to correct the body mass index to calculate the body mass index Z score, was used to evaluate the obesity status of children at the age of 7 and 10. Children were divided into four groups, including sustained non obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Meanwhile, the lung function prediction equations recommended by the Global Lung Function Initiative were used to standardize the lung function indexes of children. Pulmonary function differences among these groups were examined, and the relationship between childhood obesity and pulmonary function was longitudinally analyzed using generalized estimating equations. Results: The prevalence of obesity were 9.0% and 16.1% at the age of 7 and 10 years, respectively. The proportion of both newly classified and persistent obesity group were 8.1%, respectively. The forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) were (1 269.90±202.70) and (1 415.70±230.00) mL, respectively, at the age of 7 years. FEV 1 and FVC at the age of 10 years were (1 440.80±403.20) and (1 555.60±517.60) mL, respectively. Cross sectional analysis at age 7 showed that forced expiratory flow at 75% vital capacity (FEF 75 ) ( β=-0.52, 95%CI =-0.96--0.07) and maximal mid expiratary flow (MMEF) ( β=-0.45, 95%CI =-0.89--0.00) were significantly lower in obese children compared to their non obese peers ( P < 0.05). Longitudinal analysis indicated that obese children had lower levels of lung pulmonary function, with a statistically significant difference in FEV 1 ( β=-0.44, 95%CI=-0.85--0.02, P <0.05). There was no significant difference among the various obesity groups ( P >0.05), while gender stratified results revealed significant reductions in FEV 1/FVC in newly classified obese girls at age 10 years ( β=-1.76, 95%CI =-3.13--0.38) and in MMEF in persistently obese girls at age 10 years ( β=-1.44, 95%CI = -2.79- -0.09) ( P <0.05). Conclusion Obesity may contribute to reduced lung function levels in school aged children, with newly classified and persistent obesity having more pronounced effects on lung function in girls.

ObjectiveTo explore the mechanism of Buzhong Yiqitang in ameliorating inflammatory injury in autoimmune thyroiditis (AIT) mice based on the Toll-like receptor 4（TLR4）/nuclear transcription factor-kappa B（NF-κB）/absent in melanoma 2（AIM2）inflammasome signaling pathway. MethodThe 120 genetically susceptible 8-week-old NOD.H-2^h4 mice were selected and randomly divided into control group， model group， low， medium and high dose groups of Buzhong Yiqitang （4.78， 9.56， 19.12 g·kg^-1）， and western medicine group （selenium yeast tablets， 3.033×10^-5 g·kg^-1）. The AIT model mice in each group drank ad libitum 0.05% sodium iodide aqueous solution for 8 weeks to establish the AIT model， and the control group drank ad libitum distilled water. Eight weeks later， the mice in each dosing group were divided into groups and gavage. The swelling of thyroid tissue was observed with the naked eye， and the weight of spleen was weighed. The content of serum inflammatory factors interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， and Real-time PCR was used to detect the expression of HMGB1， TLR4， AIM2， NF-κB p65，apoptosis-associated speck-like protein（ASC），cysteinyl aspartate-specific protease-1（Caspase-1）， IL-1β mRNA. Western blot was used to detect the expression of high motility group protein 1 （HMGB1）， TLR4， AIM2， NF-κB p65， phosphorylation（p）-NF-κB p65， ASC， Caspase-1， and IL-1β proteins in thyroid tissue， and immunofluorescence staining was used to observe the protein expression of HMGB1， AIM2， and NF-κB p65 in thyroid tissue of mice. ResultCompared with the control group， the thyroid tissue of mice in the model group was significantly swollen， the spleen quality was significantly increased， and the expression of HMGB1， TLR4， NF-κB p65， AIM2， ASC， Caspase-1， IL-1β in thyroid tissue was significantly increased （P<0.01）. Compared with the model group， the swelling of thyroid tissue in mice in each dose group of Buzhong Yiqitang was improved， the quality of spleen was significantly reduced， and the expression of HMGB1， TLR4， AIM2， NF-κB p65， p-NF-κB p65， ASC， Caspase-1， IL-1β in thyroid tissue was significantly reduced （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT， and regulating the abnormal activation of the TLR4/NF-κB/AIM2 inflammasome signal pathway may be one of its intervention mechanisms.

Objective:To investigate the etiological distribution of severe community-acquired pneumonia (CAP) in children in Hebei Province.Methods:The nasopharyngeal swab samples and clinical data from 314 children with severe pneumonia were retrospectively analyzed between January 2014 and January 2016.Results:Among the 314 children, 298 (94.94%) showed positive result for pathogens in their nasopharyngeal swab samples, with 246 cases (78.34%) of multiple pathogens, predominantly mixed viruses and bacteria (206 cases, 65.61%). A total of 848 strains of pathogens were detected, including 483 strains (56.96%) of viruses, predominantly respiratory syncytial virus with 97 strains of subtype A and 86 strains of B. Bacteria and atypical pathogens ( Mycoplasma pneumoniae) had 365 strains (43.04%), mainly Streptococcus pneumoniae (220 strains) and Haemophilus influenzae (119 strains). The detection rate of pathogens was higher in children under one year of age ( χ2=21.389, P<0.001). There were no significant differences in different seasons, but the detection rates of respiratory syncytial virus A, respiratory syncytial virus B, and Streptococcus pneumoniae were higher in autumn, winter, and spring, respectively, with statistically significant differences ( χ2=22.205, P<0.001; χ2=37.874, P<0.001; χ2=11.380, P=0.009). Conclusions:Nasopharyngeal swab sample testing in children with severe pneumonia typically shows a coexistence of viral and bacterial pathogens, with detection rates varying among different age groups and seasons. Nasopharyngeal swab sample testing for pathogens provides valuable references for the identification of clinical pathogens.

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomod-ulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various im-mune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils'chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40％of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.

Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18β-GA)is a natural com-pound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18β-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18β-GA inhibited the expression of α-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon reso-nance,we found that 18β-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18β-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18β-GA in ameliorating hepatic fibrosis,highlighting the future development of 18β-GA as a novel therapeutic drug for hepatic fibrosis.

ObjectiveTo determine the complications of hypertension among local residents in Minhang district of Shanghai， and provide scientific evidence for key preventive intervention. MethodsWe retrieved the data from the electronic health records， in which hypertensive patients were included for community-based management， in Minhang district of Shanghai from January 1st， 2014 to December 31st， 2018. A total of 38 599 hypertensive patients who had not had hypertension related clinical symptom when included in the electronic health records were enrolled in our study. Chi-square test and Cochran-Mantel-Haenszel test were used to determine the complications of hypertension. ResultsThe incidence proportion of complications was 10.77%， of which cerebrovascular damage was the highest （7.44%）， followed by cardiac damage （3.55%） and peripheral vascular damage （0.81%）. The incidence proportions in patients aged 18‒59， 60‒69， 70 and above were 5.53%， 9.61% and 16.19%， respectively. There was significant difference in the incidence proportions of complications among age groups （χ²=668.670， P<0.05）. Cochran-Mantel-Haenszel test showed that in the hypertensive patients aged 60‒69， the incidence proportion of complications in females was lower than that in males （χ²=5.937， P<0.05）. However， in those aged above 70， the incidence proportion of complications in females was higher than that in males （χ²=11.619， P<0.05）. ConclusionIn patients with hypertension， the incidence proportions of cardiovascular and cerebrovascular diseases remains relatively high in Minhang district of Shanghai. Additionally， both age and gender have influence on the incidence of complications.

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Objective: To evaluate the status of dietary diversity and determinants among school age left behind children. Methods: A total of 501 children aged 9-10 years in Sheyang Mini Cohort Study were enrolled from Sheyang City in Jiangsu Province during 2019. A questionnaires survey was administrated to collect left behind and socioeconomic information. Twenty four hour dietary recall survey was conducted, dietary diversity score (DDS 10 and DDS) and food variety score (FVS) were computed according to Food and Agriculture Organization (FAO). Weight and height of children were measured and sex and age standardized body mass index was used to define obesity. Multivariable regression models were preformed to explore the determinants of dietary diversity in school age left behind children. Results: The proportion of left behind children was 40.9%. The mean value and standard deviation of three kinds of dietary diversity score (DDS 10 , DDS, FVS) in left behind children were (5.69±1.31)(6.55±1.44) and (13.48± 4.23 ), respectively. All of these were lower than that in non left behind children (DDS 10 :5.99±1.29; DDS:6.79±1.40; FVS:14.15±4.22). Significant difference in DDS 10 between left behind and non left behind children was observed ( P =0.01). The results of multivariable regression demonstrated that gender, passive smoking, family education level and family economic status were related to dietary diversity scores ( P <0.05). Conclusion Dietary diversity in school age left behind children was not optimistic and gender, passive smoking, parental education level, family economic status and left behind situation play a critical role in dietary diversity among these children.

Objective:To explore the value of laparoscopic and endoscopic cooperative surgery with the patient lying on supine position under general anesthesia in the operation of type I Mirizzi syndrome with choledocholithiasis.Methods:From Jan 2018 to Jan 2020, 53 cases of Mirizzi syndrome with choledocholithiasis undergoing laparoscopic and endoscopic cooperative surgery (preLC+ ERCP+ EST) at the Second Affiliated Hospital of Kunming Medical University were retrospectively analyzed.Results:53 patients successfully underwent LC without conversion to open surgery, and 2 patients failed in ERCP + EST attempt, with a success rate of 96.2%. One patient developed pancreas pseudocyst as a result of post-operative hemorrhagic necrotizing pancreatitis. Two patients suffered from chronic pancreatitis. Three patients complaining postoperative upper abdominal discomfort were finally diagnosed as stump cystic duct inflammation by MRCP, and no abnormalities were found in the follow-up of the remaining cases.Conclusion:Laparoscopic and endoscopic cooperative surgery in the treatment of patients with type I Mirizzi syndrome combined with choledocholithiasis is minimally invasive and effective.