OBJECTIVE To investigate the effects of metformin （Met） on liver injury in non-alcoholic steatohepatitis （NASH） rats by regulating the PI3K/AKT/PDGF signaling pathway. METHODS NASH model was constructed by feeding rats with a high- glucose and high-fat diet， and assigned into Model group， Met low-dose group （Met-L group， 100 mg/kg）， Met medium-dose group （Met-M group， 200 mg/kg）， Met high-dose group （Met-H group， 400 mg/kg）， and high dose of Met+PI3K activator group （Met-H+740 Y-P group， 400 mg/kg Met+50 mg/kg 740 Y-P）， with 12 rats in each group. Another 12 rats were regarded as the Control group. Each group of rats was orally administered/injected with the corresponding medication once a day for 6 consecutive weeks. The changes in body weight and liver index of rats were recorded and analyzed. The pathological damage [evaluation of non-alcoholic fatty liver disease activity score （NAS）]， lipid deposition （calculation of the proportion of oil red O-positive staining area）， and fibrosis （calculation of collagen deposition score） were observed in liver tissue of rats. The levels of inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）] in serum and liver tissue， the levels of serum lipid metabolism indicators [total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）] and liver function indicators [aspartate aminotransferase （AST） and alanine Δ 基金项目 武汉市知识创新专项项目（No.2022020801010588）； aminotransferase （ALT）] were measured. The expression levels of PI3K/AKT/PDGF signaling pathway-related proteins and Caspase-3 in liver tissue of rats were determined. RESULTS Compared with the Control group， body weight， liver index， the levels of serum lipid metabolism indicators and liver function indicators， the levels of IL-6 and TNF-α in serum and liver tissue， the NAS， the proportion of oil red O-positive staining area， the collagen deposition fraction， and the levels of phosphorylated PI3K and AKT proteins， as well as the expression levels of PDGF and Caspase-3 proteins in liver tissue， were all significantly increased （P＜0.05）. The liver tissue showed severe pathological damage， characterized by an abundance of lipid droplets and pronounced collagen deposition. After the intervention with Met， the aforementioned quantitative indicators and pathological changes in rats were significantly improved in a dose- dependent manner （P＜0.05）. 740 Y-P could reverse the improvement effects of high dose of Met on the above indexes of rats （P＜ 0.05）. CONCLUSIONS Met can improve liver damage， and alleviate inflammatory reactions and liver fibrosis of NASH rats， the mechanism of which may be associated with inhibiting PI3K/AKT/PDGF signaling pathway.

OBJECTIVE To investigate the intervention effect of kushenol F （KSC-F） on ulcerative colitis （UC） mice. METHODS Totally 30 male C57BL/6J mice were randomly divided into the normal group， model group， positive drug group （sulfasalazine， 703 mg/kg）， KSC-F 50 mg/kg group （KSC-F50 group）， and KSC-F 100 mg/kg group （KSC-F100 group）， with 6 mice in each group. Except for the normal group， the mice in the remaining groups were given 3% dextran sulfate sodium solution continuously for 7 days to induce UC model. Concurrently， administration groups received corresponding drug solution intragastrically， once a day， for 10 consecutive days. During the experiment， the changes in body weight and bowel movements of the mice were observed. Disease activity index scoring was performed after the last administration. The histopathological morphology of colonic tissue was examined. The levels of inflammatory factors in the serum and colon tissue were measured. Additionally， the mRNA expression of inflammatory factors， and the protein expressions of inflammation-related proteins [interleukin-1β （IL-1β）， forkhead box O1（FOXO1）， phosphoinositide 3-kinase（PI3K）， phosphorylated PI3K（p-PI3K）， p38 mitogen-activated protein kinase（p38 MAPK）， phosphorylated p38 MAPK（p-p38 MPAK） and phosphorylated protein kinase B（p- Akt）] were determined in colonic tissue. RESULTS KSC-F could alleviate weight loss and colonic tissue damage in UC mice. KSC- F reduced the levels of IL-1β， IL-6， IL-8 and tumor necrosis factor-α （TNF-α） in serum， as well as IL-1β， IL-6， IL-17 and TNF- α in colonic tissue to varying degrees and increased the levels of IL-10 in both serum and colonic tissue （P＜0.05 or P＜0.01）. Moreover， KSC-F decreased the expression levels of IL-1β， IL-17 and TNF-α mRNA， as well as p-PI3K， p-p38 MAPK， and p- Akt proteins in colonic tissue to varying degrees， and increased the expression levels of IL-10 mRNA and FOXO1 protein in colonic tissue （P＜0.05 or P＜0.01）. CONCLUSIONS KSC-F effectively alleviates UC symptoms in mice by inhibiting PI3K， Akt and p38 MAPK activation， mitigating the release of pro-inflammatory factors such as IL-1β， IL-6， TNF- α，promoting the anti-inflammatory factor IL-10 secretion， and reducing inflammation-induced colonic tissue damage.

Objective To analyze the epidemic status of newly diagnosed occupational diseases in Guangdong Province during the “13th Five-Year Plan” period, and scientifically evaluate the critical risk factors for occupational disease prevention and control. Methods The data of newly diagnosed occupational diseases reported by internet in Guangdong Province from 2016 to 2020 was collected from Report Card of Occupational Diseases using Occupational Diseases and Health Hazard Factors Monitoring Information System under China Disease Prevention and Control Information System. Data was used to determine the epidemic status and identify key risk factors. Results A total of 4 846 cases of occupational diseases were reported in Guangdong Province during the “13th Five-Year Plan”period, with an increase rate of 39.13% compared with the “12th Five-Year Plan” period (3 483 cases). The annual distribution of newly diagnosed occupational disease cases showed a trend of increasing and then declining. The top five percentage on types of occupational diseases were occupational noise-induced deafness, occupational silicosis, occupational chronic benzene poisoning, other occupational pneumoconiosis and occupational hand-arm vibration disease, accounting for 45.23%, 16.28%, 11.52%, 7.92% and 4.60%, respectively. Cases from the Pearl River Delta region accounted for 92.76%, while five non-Delta cities had “zero reported cases”. Regarding industry sector, cases were primarily concentrated in manufacturing, construction, and mining, accounting for 84.21%, 5.49% and 3.59%, respectively. Regarding industry categories, cases were concentrated in metal products, non-metallic mineral products, manufacturing of cultur, education, art, sports and entertainment goods, manufacturing of computer, communication and other electric devices, and manufacturing of specialized equipment, accounting for 11.70%, 10.17%, 8.60%, 7.82%, and 4.81%, respectively. A total of 196 enterprises (accounting for 7.39%) reported an average of three or more new cases per year, while 19 enterprises (accounting for 0.72%) reported an average of ten or more cases per year. Conclusion The epidemic status of occupational diseases in Guangdong Province showed a “triple concentration” characteristic in disease types, regions, and industries during the “13th Five-Year Plan” period. Particular attention should be paid to epidemic status of occupational noise-induced deafness, occupational silicosis, occupational chronic benzene poisoning, other occupational pneumoconiosis, and occupational hand-arm vibration disease, and also pay special attention to the prevention and control of occupational diseases in the Pearl River Delta region, cities with “zero reported cases”, manufacturing industry and occupational disease-prone enterprises.

Objective The occurrence of chickenpox in rapidly developing areas poses substantial seasonal risk to children.However,certain factors influencing local chickenpox outbreaks have not been studied.Here,we examined the relationship between spatial clustering,heterogeneity of chickenpox outbreaks,and socioeconomic factors in Southern China. Methods We assessed chickenpox outbreak data from Southern China between 2006 and 2021,comprising both relatively fast-growing parts and slower sub-regions,and provides a representative sample of many developing regions.We analyzed the spatial clustering attributes associated with chickenpox outbreaks using Moran's I and local indicators of spatial association and quantified their socioeconomic determinants using Geodetector q statistics. Results There were significant spatial heterogeneity in the risk of chickenpox outbreaks,with strong correlations between chickenpox risk and various factors,particularly demographics and living environment.Furthermore,interactive effects among specific are factors,such as population density and per capita residential building area,percentage of households with toilets,percentage of rental housing,exhibited q statistics of 0.28,0.25,and 0.24,respectively. Conclusion This study provides valuable insights into the spatial dynamics of chickenpox outbreaks in rapidly developing regions,revealing the socioeconomic factors affecting disease transmission.These implications extend the formulation of effective public health strategies and interventions to prevent and control chickenpox outbreaks in similar global contexts.

OBJECTIVE To explore the action mechanism of kushenol F （KSCF） in treating ulcerative colitis （UC） in mice. METHODS The potential targets of KSCF intervening in UC were predicted with network pharmacology and molecular docking. C57BL/6J mice were randomly divided by body weight into model group， positive control group （sulfasalazine， 703 mg/kg）， KSCF group （100 mg/kg）， and normal group， with 6 mice per group. The UC model of mice was induced by dextran sulfate sodium solution. During the modeling period， the mice were given relevant medicine intragastrically， once a day， for 7 consecutive days. After the last administration， the disease activity index （DAI） of the mice was scored； the length of the mice’s colon was measured； pathological changes in the colon tissue of mice were observed； the levels of lipopolysaccharide （LPS） in serum， myeloperoxidase （MPO）， nitric oxide （NO） and superoxide dismutase （SOD） in the colon were detected in mice； the expression levels of occludin and ZO-1 in colon tissue of mice were detected； the proportions of CD3+T， CD4+T， and CD8+T lymphocytes in the spleen and the ratio of CD4+/CD8+ were detected； changes in colonic microbiota were analyzed by 16S rDNA sequencing. RESULTS Results of network pharmacology indicated that KSCF may treat UC by regulating signaling pathways such as phosphatidylinositol-3 kinase/protein kinase B （PI3K/AKT） and nuclear factor kappa B （NF- κB）. Molecular docking results showed that KSCF bound most stably with NF-κB p65 protein. Animal experiment results demonstrated that， compared with the model group， the pathological characteristics of colon tissue in mice were improved in KSCF group. DAI scores， serum levels of LPS， the levels of MPO，NF-κB p65 phosphorylation and NLRP3 protein expression in the colon， and the proportion of CD8+T lymphocytes in the spleen were reduced significantly （P＜0.05）. Body weight， SOD levels， expression levels of occludin and ZO-1 in the colon， proportions of CD3+T and CD4+T lymphocytes， and the CD4+/CD8+ ratio in the spleen were significantly increased （P＜0.05）； the abundance of Firmicutes， Actinobacteria， Akkermansia， and Lactobacillus genera were increased， while Proteobacteria decreased； the microbial community structure tended towards that of the normal group. CONCLUSIONS KSCF alleviates UC by restoring intestinal microbial imbalance， enhancing immune response， and inhibiting colonic inflammatory responses， thereby improving intestinal barrier integrity.

ObjectiveTo investigate the possible mechanism of modified Gegen Qinlian Decoction （葛根芩连汤） in treatment of ulcerative colitis （UC） from the view of intestinal mucosal epithelial barrier damage and epithelial mesenchymal transition. MethodsSixty male C57BL/6J mice were divided into blank group， model group， western medicine control group， and low-， medium-， and high-dose modified Gegen Qinlian Decoction groups， with 10 mice in each group. Except for the blank group， 3% dextran sodium sulfate （DSS） was used to induce colitis model by free drinking for 7 days， and on the first day of modelling， 6， 12， and 24 g/（kg·d） of modified Gegen Qinlian Decoction were given to the low-， medium-， and high-dose groups respectively， 5-aminosalicylic acid （5-ASA） 100 mg/（kg·d） given by gavage to western medicine control group， and 10 ml/kg distilled water were given to blank and model group by gavage， once a day for 7 days. Body mass of mice was recorded and disease activity index （DAI） scores were performed daily. The mice were anesthetized after 24h of the last administration and the colon was taken to observe the length of colon， HE staining was applied to observe the damage of colonic mucosa and score pathological states， Masson staining to detect the deposition of colonic collagen fibers， immunofluorescence to observe the distribution of F-actin in colonic mucosal epithelium， and immunohistochemistry to detect the expression of tight junction protein ZO-1， Occludin， E-cadherin and Vimentin. ResultsCompared with the blank group at the same time， the percentage of body mass of mice in the model group on day 7 of modelling significantly reduced and the DAI score was significantly increased （P＜0.01）； compared with the model group at the same time， the body mass of mice in the western medicine control group and all of modified Gegen Qinlian Decoction groups decreased， and the DAI scores of mice in the western medicine control group and the high-dose modified Gegen Qinlian Decoction group decreased （P＜0.05 or P＜0.01）； compared with the same time of mice in the low-dos Gegen Qinlian Decoction group， the body mass of mice in the high-dose Gegen Qinlian Decoction group and the western medicine control group significantly elevated （P＜0.05）. Compared with the blank group， the length of the colon of mice in the model group was significantly shortened， the pathological score and the percentage of collagen area were significantly increased， the average fluorescence intensity of F-actin was reduced， the protein levels of ZO-1， Occludin and E-cadherin in the colon tissue decreased， and the protein level of Vimentin elevated （P＜0.01）. Compared with the model group， the length of colon significantly increased， patholo-gical score， collagen area percentage decreased， ZO-1， Occludin， E-cadherin protein levels increased and Vimentin levels decreased in all medicated groups； the average fluorescence intensity of F-actin increased in the western medicine control group and the middle- and high-dose Gegen Qinlian Decoction groups （P＜0.05 or P＜0.01）. Compared with the low-dose Gegen Qinlian Decoction group， the proportion of collagen fibre area in the middle-dose Gegen Qinlian Decoction group and the western medicine control group reduced； the mean fluorescence intensity of F-actin increased in the middle-dose Gegen Qinlian Decoction group； the protein levels of ZO-1 and E-cadherin increased in the western medicine control group， and the protein levels of ZO-1 increased in the high-dose Gegen Qinlian Decoction group （P＜0.05）. Compared with the medium-dose Gegen Qinlian Decoction group， the protein levels of ZO-1 elevated in the high-dose Gegen Qinlian Decoction group （P＜0.05）. Comapred with the high-dose Gegen Qinlian Decoction group， level of E-cadherin and Vimentin protein of the western medicine control group increased （P＜0.05）. ConclusionModified Gegen Qinlian Decoction was able to reduce colonic inflammation and mucosal barrier damage and inhibit the process of epithelial mesenchymal transition in mice models of ulcerative colitis， which may be one of its action mechanisms .

AIM:To investigate the impact of honokiol(HKL),an activator of silent information regulator 3(SIRT3),on postoperative cognitive dysfunction(POCD)in mice,and to explore the potential mechanisms.METHODS:Ten-month-old male C57/BL6 mice were randomly divided into control(Con)group,surgical(Sur)group and Sur+HKL group(n=10).The mice in Sur+HKL group were intraperitoneally injected with HKL for 7 d before modeling.The mice in Sur and Sur+HKL groups underwent tibial fracture open reduction and internal fixation to establish the POCD model.The assessment of cognitive function was conducted using the open-field test(OFT),novel object recognition test(NORT),Morris water maze test(MWMT),and Y-maze test(YMT).Nissl staining was employed to assess the morphology,struc-ture and vitality of hippocampal and cortical neurons in mice.The protein expression of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),acyl coenzyme A synthetase long-chain family member 4(ACSL4),SIRT3 and nuclear factor E2-related factor 2(NRF2)in the mouse hippocampus was detected by Western blot,while im-munofluorescence staining was utilized to determine GPX4 level in mouse neurons.RESULTS:No statistically signifi-cant differences were observed among the groups in terms of total distance moved and central zone exploration during the OFT(P>0.05).However,the results from the NORT and YMT indicated that the mice in Sur group exhibited significant-ly lower recognition indexes,reduced alternation rates(P<0.01),and decreased percentages of entries and crossing time into the new arm after side arm blockade(P<0.01),when compared with Con group.Furthermore,the mice in Sur group demonstrated a slower decrease in latency during the learning period of MWMT,while significantly lower latency,fewer crossing number and lower percentage of time in the target quadrant were observed during the testing period of MWMT(P<0.01).The above indicators were obviously enhanced in Sur+HKL group compared with Sur group(P<0.01).The results of Nissl staining indicated lighter neuronal staining in the hippocampal CA1 region and medial prefrontal cortex in Sur group,accompanied by a significant reduction in the number of Nissl-stained positive neurons(P<0.01).Notably,HKL pretreatment demonstrated a significant improvement in neuronal vitality.Analysis of Western blot revealed that compared with Con group,the expression of SIRT3,GPX4,SLC7A11 and NRF2 in Sur group was significantly reduced,while the expression of ACSL4 was significantly increased(P<0.05).However,these alterations were reversed after treatment with HKL(P<0.05).Immunofluorescence staining of hippocampal neurons corroborated the findings from Western blot analy-sis,demonstrating a notable decrease in GPX4 expression in hippocampal neurons of Sur group,which was significantly restored after HKL pretreatment(P<0.01).CONCLUSION:Treatment with HKL attenuates POCD in mice,potentially through its inhibitory effect on hippocampal neuronal ferroptosis.

Objective:To explore the views of adolescents with asthma on factors affecting disease self-management, so as to provide a basis for improving self-management of asthma children, and propose improvement suggestions.Methods:This study was a descriptive qualitative study. From February to June 2023, 10 to 17 year old children with asthma were recruited at the Asthma Clinic of the Children's Hospital affiliated to Capital Institute of Pediatrics through purposive sampling. One-on-one semi-structured interviews were conducted around self-management and its related factors, and the thematic analysis was used to analyse interview materials.Results:A total of 17 adolescents with asthma, aged (13.00±2.03) years, with a course of disease of (5.00±2.85) years, were included. The interview materials included two aspects, namely facilitators and barriers of self-management. The facilitators were coded into three themes and seven sub-themes, including the individual management awareness of children with asthma (sense of responsibility, compliance awareness), social support (parental care and compensation, teacher and classmate support, patient interaction), and health education (health guidance from doctors and nurses, school health propaganda). Barriers were encoded into three themes and six sub-themes, including disease cognition (demand competition, importance), social environment (interpersonal interaction, physical environment), and healthcare services (accessibility of medical services, school related medical resources) .Conclusions:The self-management of adolescents with asthma is affected by multiple factors. Individual management awareness, social support, and health education can promote self-management in children with asthma, while unfavorable factors in disease cognition, social environment, and healthcare services can hinder self-management in children with asthma. Medical and nursing staff should develop and implement empowerment plans for self-management of asthma children, by mobilizing multi-channel medical resources, providing multi-dimensional full process empowerment, and helping asthma children build a diverse interpersonal support network system, in order to promote effective health management transition for adolescents with asthma.

Objective To investigate the effect of intestinal mucosal Toll-like receptor 4/nuclear factor κB (TLR4/NF-κB) signaling pathway on renal damage in pseudo-sterile IgA nephropathy (IgAN) mice. Methods C57BL/6 mice were randomly divided into experimental group (pseudosterile mouse model group), control group (IgAN mouse model group), pseudosterile mouse blank group, and normal mouse blank group. Pseudosterile mice were established by intragastric administration of quadruple antibiotics once a day for 14 days. The pseudosterile IgAN mouse model was set up by combination of oral bovine serum albumin (BSA) administration and staphylococcal enterotoxin B (SEB) injection. The pathological changes of renal tissue were observed by immunofluorescence staining and PAS staining, and the intestinal mucosa barrier damage indicators lipopolysaccharide(LPS), soluble intercellular adhesion molecule 1(sICAM-1) and D-lactate(D-LAC) were analyzed by ELISA. Biochemical analysis was used to test 24 hour urine protein, serum creatinine and blood urea nitrogen. The mRNA and protein levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor κB (NF-κB) were detected by reverse transcription PCR and Western blot analysis. Results The kidney damage of pseudosterile IgAN mice was more severe than that of IgAN mice, and the expressions of intestinal mucosal barrier damage markers (LPS, sICAM-1 and D-LAC) were significantly increased in pseudosterile IgAN mice. In addition, the expressions of TLR4, MyD88, and NF-κB level were all up-regulated in the intestinal tissues of IgAN pseudosterile mice. Conclusion Intestinal flora disturbance leads to intestinal mucosal barrier damage and induces activation of TLR4 signaling pathway to mediate renal injury in IgAN.
Animals ; Mice ; Mice, Inbred C57BL ; Glomerulonephritis, IGA ; NF-kappa B ; Toll-Like Receptor 4/genetics* ; Lipopolysaccharides ; Myeloid Differentiation Factor 88/genetics* ; Kidney ; Intestinal Mucosa ; Infertility ; Disease Models, Animal

This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.
Humans ; China/epidemiology* ; Cross Infection/epidemiology* ; Intensive Care Units/statistics & numerical data* ; Quality Control ; Quality Indicators, Health Care/statistics & numerical data* ; Sepsis/therapy* ; East Asian People/statistics & numerical data*