ObjectiveTo investigate the mechanism of Xiaozhi Qinggan decoction （XQD） in preventing and treating metabolic dysfunction-associated steatotic liver disease （MASLD） by regulating ferroptosis， network pharmacology， in vitro and in vivo experiments. MethodsIn the in vivo experiment， mouse MASLD models were established by high-fat diet （HFD） induction. The model mice were randomly assigned to a positive control group （silybin， 50 mg·kg^-1）， low-， medium- and high-dose XQD groups （4.725， 9.45， 18.9 g·kg^-1）， with a normal control group. After 4 weeks of modeling， mice except the normal group were administered intragastrically for 8 consecutive weeks. Liver function， serum lipid levels， hepatic histopathology， as well as the levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， reduced glutathione （GSH） and oxidized glutathione （GSSG） and Fe²⁺ were detected. The mRNA and protein expression of p53， SLC7A11 and GPX4 were determined by quantitative Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot. In the network pharmacology analysis， active components and potential targets of XQD for MASLD were screened， followed by functional and pathway enrichment analyses， and molecular docking was performed to verify the target binding activity. In the in vitro experiment， the optimal concentration of XQD-containing serum was screened by cytotoxicity assay. HepG2 cells were transfected with ov-NC or ov-p53 plasmid， and a lipid accumulation model was induced by free fatty acid （FFA， 1.0 mmol·L^-1）. Cells were divided into a normal group， FFA model group， ov-NC+XQD （15%） group and ov-p53+XQD （15%） group. Intracellular Fe²⁺ level and lipid accumulation were evaluated， and the protein expression of p53， SLC7A11 and GPX4 was measured by Western blot. ResultsCompared with the normal group， the model group exhibited markedly elevated body weight， liver weight， liver index， fasting blood glucose， AUC of glucose tolerance test， serum liver function and blood lipid levels at week 12 （P<0.01）. Hepatic steatosis and inflammatory infiltration were observed by pathological staining. Additionally， hepatic levels of MDA， SOD and Fe²⁺ were increased （P<0.01）， while GSH， GSSG and the GSH/GSSG ratio were decreased （P<0.01）. The mRNA and protein expression of hepatic p53 was upregulated （P<0.01）， whereas the expression of SLC7A11 and GPX4 was downregulated （P<0.01）. Compared with the model group， the low- and medium-dose XQD groups showed significantly decreased body weight at week 12 （P<0.05）. The silybin group， together with the medium- and high-dose XQD groups， presented reduced liver weight and liver index （P<0.05）. Fasting blood glucose and the AUC of glucose tolerance test were lowered in all four treatment groups （P<0.05， P<0.01）. Pathological staining revealed alleviated hepatic steatosis and inflammation， accompanied by decreased serum liver function and blood lipid levels （P<0.05， P<0.01）. Moreover， hepatic MDA and SOD levels were markedly reduced， while GSH， GSSG and the GSH/GSSG ratio were significantly elevated （P<0.05， P<0.01）. Hepatic Fe²⁺ level was decreased （P<0.01）. The mRNA and protein expression of hepatic p53 was downregulated， and the expression of SLC7A11 and GPX4 was upregulated （P<0.05， P<0.01）. Network pharmacology analysis identified quercetin， kaempferol， luteolin， tanshinone IIA and isorhamnetin as the core active components of XQD， with p53 serving as the key target. Stable binding was verified between these active components and the p53 protein. The optimal concentration of XQD-containing serum in vitro was determined to be 15%. Compared with the normal group， the model group showed increased intracellular Fe²⁺ and lipid accumulation， significantly upregulated p53 protein expression （P<0.01）， and markedly downregulated SLC7A11 and GPX4 protein expression （P<0.01）. Compared with the model group， the ov-NC group exhibited reduced Fe²⁺ and lipid accumulation， downregulated p53 expression， and upregulated SLC7A11 and GPX4 expression. In the ov-p53 group， p53 expression was upregulated （P<0.01）， while SLC7A11 and GPX4 expression was downregulated （P<0.01）. ConclusionXQD inhibits ferroptosis by downregulating p53 and upregulating SLC7A11 and GPX4， thereby alleviating oxidative stress and lipid peroxidation in hepatocytes and improving MASLD.

Work-related musculoskeletal disorders (WMSDs) represent a significant occupational health challenge among healthcare professionals globally, posing substantial threats to physical and mental well-being as well as work sustainability. Adopting preventive behaviors—including ergonomic postural adjustments, optimized work-rest scheduling, proper use of protective and assistive equipment, and regular physical activity—is essential for mitigating the risk of WMSDs. Guided by the social ecological model, the review synthesized current evidence on the determinants of WMSDs preventive behaviors across four levels: intrapersonal characteristics, work environment conditions, interpersonal support, and policy/institutional factors. The findings suggest that higher educational attainment, favorable health-related behavioral patterns, optimized ergonomic work environments, adoption of supportive collaborative systems, strong organizational support, as well as policy safeguards facilitate preventive behavior adoption. Conversely, limited prevention-related knowledge, low risk perception, insufficient physical activity, excessive workload, lack of appropriate protective equipment, inadequate ergonomic training, a prevailing culture of presenteeism, and inadequate policy implementation constitute significant barriers. Multi-dimensional intervention strategies targeting these determinants are warranted to enhance preventive behaviors, reduce the risk of WMSDs, and strengthen occupational health protection for healthcare professionals.

It is considered that lean metabolic associated fatty liver disease （MAFLD） is characte-rized by a state of "lean body but fatty liver". From the perspective of the pathomechanism evolution of "spleen failing to disperse essence， while kidney failing to transform qi"， the disease is systematically treated under the principle that spleen and kidney deficiency as the root and liver constraint with phlegm stasis as the branch. Spleen deficiency with impaired transformation and transportation leads to failure in the distribution of refined substances， initiating lipid turbidity accumulation and obstruction. Kidney dysfunction in qi transformation results in insufficient essence and blood， forming the root of bodily malnourishment. Over time， this further gives rise to liver constraint and loss of dispersing function， disorder in the movement of essential substances， and congealing of phlegm and stasis within hepatic collaterals. The dysfunction of three organs including spleen， kidney and liver constitutes the pathological basis of metabolic disturbances involving qi， blood， body fluids and essence. Treatment should follow the principle of "nourishing the healthy qi leads to spontaneous resolution of pathogenic accumulation"， with three approaches. First， fortifying the spleen and eliminating dampness， using Sini Powder （四逆散） and Erchen Pingwei Powder （二陈平胃散） to restore the transport and transformation function of the middle jiao （焦）， thereby guiding essential substances back to their proper physiological pathways. Second， tonifying the kidney and resolving turbidity， using Jinkui Shenqi Pill （金匮肾气丸） and Effective Integration Decoction （一贯煎） to replenish the lower jiao， promoting the restoration of essence and the transformation of turbid pathogen. Third， soothing the liver and resolving stasis， using Liujunzi Decoction （六君子汤） and Xiaozhi Qinggan Decoction （消脂清肝汤） to vent qi and blood stagnation， thereby interrupting disease progression. Together， these three methods reinforce healthy qi while eliminating pathogen， facilitating the restoration of proper essence transformation and the resolution of lipid turbidity.

It is proposed that the core pathogenesis of porto-sinusoidal vascular disease （PSVD） is characterized by deficiency of healthy qi with collateral stagnation and the binding of stasis and toxin. According to the characteristics of its microvascular lesions， PSVD can be treated through syndrome differentiation in three stages， including the occult stage， progressive stage， and decompensated stage. Considering the properties of insect-derived medicinals， such as rapid movement， penetrating action， and ability to search out pathogen and unblock collaterals， three therapeutic principles are established， which are unblocking collaterals， softening the liver， and dispelling pathogen. Clinically， the New-Modified Chaihu Biejia Decoction （柴胡鳖甲汤） is used as the basic prescription with staged modifications. During the occult stage， medicinals such as Quanxie （Scorpio） and Wugong （Scolopendra） are added to search out pathogen， unblock collaterals， and protect the channels from progression. During the progressive stage， Tubiechong （Eupolyphaga seu Steleophaga） and Qianglang （Catharsius molossus） are added to dispel stasis and soften hard masses， thereby removing concretions and dissipating masses. During the decompensated stage， Shuizhi （Hirudo） and Dilong （Pheretima） are added to eliminate stasis and promote urination， treating blood and fluid retention simultaneously.

Background Chronic non-communicable diseases, including hypertension, have become major threats to urban public health. The built environment has been linked to blood pressure. Objective To examine joint exposure patterns of built environment factors in relation to residents' blood pressure status and to identify environmental profiles of neighborhoods that may be favorable or unfavorable to hypertension prevention. Methods (1) A cross-sectional study was conducted among 1910 residents in Longzihu District, Bengbu City. Demographic characteristics, clinical indicators (including blood pressure), and lifestyle behavioral data were collected. Nine built environment indicators were derived within a 500-meter buffer zone surrounding each participant's residential address. (2) Using elevated blood pressure status as a binary outcome (all residents) and grade of elevated blood pressure as an ordinal multi-class outcome (residents with elevated blood pressure), the predictive performance of four binary classification models and nine multi-class classification models was compared, respectively. Feature importance was ranked based on the best-performing model. Multi-variable logistic regression with stepwise adjustment was then used to identify key environmental factors. (3) Using partial dependence plots, a joint exposure analysis was conducted in the target population of residents with elevated blood pressure (high-normal blood pressure and hypertension grades 1–3), with the 25th and 75th percentiles of key environmental factors as the low- and high-level thresholds, respectively. The 95% confidence intervals were estimated using the Bootstrap method. Results (1) Among the study participants, 863 had elevated blood pressure: 349 (40.4%) had high-normal blood pressure, and 398 (46.1%), 93 (10.8%), and 23 (2.7%) had hypertension grades 1, 2, and 3, respectively. (2) Logistic regression showed the best performance in analyzing the association between built environment factors and elevated blood pressure status (n=1910), whereas random forest showed the best performance in analyzing the association between built environment factors and grade of elevated blood pressure (n=863). Road density, bus stop density, and hospital/clinic density were key environmental factors. (3) Pairwise joint exposure patterns were observed among the three key environmental factors: When any two were both below the low-level thresholds (road ≤0.54 km·km⁻², bus stop ≤0.51 points·km⁻², hospital ≤5.99 points·km⁻²), the risk of a higher grade of elevated blood pressure was greater than the overall sample average (relative predicted odds 1.29–1.31, 95% confidence interval lower bound >1); when any two were both above the high-level thresholds (road ≥0.75 km·km⁻², bus stop ≥1.25 points·km⁻², hospital ≥15.00 points·km⁻²), the risk was lower than the overall sample average (relative predicted odds 0.54–0.61, 95% confidence interval upper bound <1); low-high and high-low combinations did not differ significantly from the overall sample average (P > 0.05). Conclusion Joint exposure profiles characterized by road density, bus stop density, and hospital/clinic density are associated with elevated blood pressure among residents: Simultaneously low levels of any two of these environmental indicators are associated with a higher predicted risk of a more severe grade, whereas simultaneously high levels are associated with a lower predicted risk. These findings suggest that coordinated configurations of road networks, public transit accessibility, and medical service facilities may represent important environmental feature of neighborhoods favorable to hypertension prevention and control.

BACKGROUND:Rheumatoid arthritis is an inflammatory disease.Many studies have shown that wogonin has a good anti-inflammatory effect on rheumatoid arthritis,but its exact efficacy and specific mechanism of action remain to be clarified. OBJECTIVE:To investigate the mechanism of wogonin ameliorating joint inflammation by regulating endoplasmic reticulum stress pathway in rats with collagen-induced arthritis. METHODS:(1)At the animal level:Female Wistar rats were divided into healthy control group,arthritis model group and wogonin treatment group.Rat models of arthritis in the latter two groups were established by subcutaneous injection of bovine type Ⅱ collagen and adjuvant.In the wogonin group,wogonin was given by gavage for 28 consecutive days after modeling.During this period,the rats in each group were weighed,and arthritis score and ankle swelling were measured every 7 days.After the experiment,the pathological changes of the joint were observed,the mRNA and protein levels of endoplasmic reticulum stress pathway GRP78 and CHOP were detected by qRT-PCR,western blot,and immunohistochemistry.(2)At the cellular level,cell counting kit-8 was used to detect the cytotoxic effect of wogonin on fibroblast-like synoviocytes from rats with collagen-induced arthritis.The fibroblast-like synoviocytes induced by thapsigargin were treated with different concentrations of wogonin.The levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant were detected by ELISA,and the intracellular reactive oxygen species in each group were determined by DCFH-DA probe method.The mRNA and protein levels of GRP78,IRE1α,XBP1s and CHOP were detected by qRT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the healthy control group,arthritis index score and ankle swelling degree in the arthritis model group were increased(P<0.01),synovial hyperplasia,inflammatory cell infiltration,cartilage destruction and bone erosion were observed in pathological sections,and the mRNA and protein expressions of GRP78 and CHOP in the ankle were significantly increased(P<0.01),which were mainly located in synovial tissue and articular surface.Compared with the arthritis model group,the arthritis index score and ankle swelling degree in the wogonin treatment group were decreased(P<0.05),synovial hyperplasia and the number of inflammatory cells were decreased,cartilage destruction and bone erosion were alleviated,the mRNA and protein expression levels of GRP78 and CHOP in the ankle were decreased(P<0.05),particularly in synovial tissue and on the articular surface.There was no significant difference in body mass among the three groups(P>0.05).In the cell experiment,200 μmol/L wogonin significantly reduced the survival rate of fibroblast-like synoviocytes(P<0.01).Compared with the blank control group,the levels of interleukin-1β,tumor necrosis factor-α,content of reactive oxygen species,and mRNA and protein expression of GRP78,IRE1α,XBP1s,and CHOP in the thapsigargin group were significantly increased(P<0.05);compared with the thapsigargin group,50 and 100 μmol/L wogonin significantly reduced the levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant(P<0.05,P<0.01),and 100 μmol/L wogonin significantly reduced the content of reactive oxygen species(P<0.01)and down-regulated the mRNA and protein expression levels of GRP78,IRE1α,XBP1s and CHOP(all P<0.05).These results suggest that wogonin can effectively alleviate joint inflammatory responses in rats with collagen-induced arthritis,and the endoplasmic reticulum stress pathway may be the key target of its intervention.

BACKGROUND:Our previous study found that Modified Erxian Pill could alleviate inflammation in collagen-induced arthritis rats,but its mechanism needs to be further verified. OBJECTIVE:To analyze the components absorbed in the blood of Modified Erxian Pill,and observe the effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages. METHODS:(1)Analysis of components absorbed in the blood of Modified Erxian Pill:Ultra-high performance liquid chromatography-high resolution mass spectrometry was used to detect and identify Modified Erxian Pill and its components absorbed in the blood.(2)Effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages:Molecular docking technology was used to initially verify the sesquiterpenoids and NLRP3 in components absorbed in the blood of Modified Erxian Pill.J774A.1 macrophages were randomly divided into blank control group,lipopolysaccharide+adenosine triphosphate group,and lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill with low(2.5%),medium(5%),and high(10%)dose groups.The release of lactate dehydrogenase in the cell supernatant of each group was detected according to the kit instructions.The levels of interleukin-1β and interleukin-18 in cell supernatant were detected in each group by ELISA.The cell membrane damage was detected by Hoechst/PI staining.The expression levels of NLRP3,Caspase-1,GSDMD,and GSDMD-N protein in the cells of each group were detected by western blot assay. RESULTS AND CONCLUSION:(1)A total of 32 active components of Modified Erxian Pill were identified,and 21 components entered the blood.The main components into blood included a variety of sesquiterpenoids.(2)Molecular docking results showed that 3-O-Acetyl-13-deoxyphomenone,Incensol oxide,Atractylenolide III,Rupestonic acid,and 3,7-Dihydroxy-9,11-eremophiladien-8-one had good binding activity with NLRP3.(3)Compared with the blank control group,lactate dehydrogenase activity and the expression levels of interleukin-1β and interleukin-18 were significantly increased in cell supernatant of lipopolysaccharide+adenosine triphosphate group(P<0.001).Hoechst/PI staining showed that the number of PI-positive cells was significantly increased.After the intervention of lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group,all of them showed different degrees of reduction.(4)Compared with the blank control group,NLRP3,Caspase-1,GSDMD,and GSDMD-N protein expression levels were significantly increased in the lipopolysaccharide+adenosine triphosphate group(P<0.05).Compared with lipopolysaccharide+adenosine triphosphate group,the protein expressions of NLRP3,Caspase-1,GSDMD,and GSDMD-N were significantly decreased in the lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group(P<0.05),and had a certain dose dependence.These findings verify that the drug-containing serum of Modified Erxian Pill may inhibit the pyroptosis of J774A.1 macrophages by regulating the NLRP3/Caspase-1/GSDMD pathway.

Objective To examine the significance of susceptible gene detection for hereditary cancer syndrome (HCS) among general population. Methods A total of 2 928 individuals undergoing routine health examinations in Healthcare Center of Zhongshan Hospital, Fudan University, from September 2021 to April 2024 were enrolled retrospectively. Next generation sequencing was employed to identify susceptible genes for HCS. American College of Medical Genetics and Genomics (ACMG) guideline was used to analyze the pathogenicity of variants. Clinical data, imagings, follow-up data were also collected. Results The overall mutation rate of HCS panel was 3.59% (105/2 928), with 0.61% (18/2 928) for MutY DNA glycosylase (MUTYH), 0.27% (8/2 928) for breast cancer susceptibility gene 1/2 (BRCA1/2) and 0.23% (7/2 928) for mismatch repair (MMR) genes. Conclusions Healthy individuals carrying tumor susceptible genes usually lack the relevant clinical phenotypes. Whether comprehensive testing needs to be carried out among healthy people remains to be further explored.

Objective To understand the detection rate of children with phenylketonuria(PKU)in southern Xinjiang in recent 10 years,and analyze the mutation of phenylalanine hydroxylase(PAH)gene in children with classical PKU in southern Xinjiang,so as to provide effective reference for clinical treatment.Methods The concentration of phenylalanine(PHE)in dried filter paper blood was de-tected by chemical fluorescence method for PKU screening of live births in southern Xinjiang.The heel blood or venous blood of 29 Uygur PKU children diagnosed in southern Xinjiang were collected.The exons 10,11,12 of PAH gene and the intron junction region of Uygur PKU children were sequenced by polymerase chain reaction(PCR)product direct sequencing method to determine the mutation site.Results A total of 5gene mutation types and 13mutation sites were detected in 58 chromosomes,and the mutation detection rate was 44.83％(13/29).The five mutations were divided into two mutation sites of ivs10-1(c.1066-11g＞a)in the junction region be-tween exon 10 and intron,and four P L3851(c.1155g＞c)mutation site,4 exon 12 P R413p(c.1238g＞c)mutation site,1 exon 12 P T418p(c.1252a＞c)mutation site,two ivs12+1(c.1315+1g＞a)mutation sites in exon 12;Two site mutations were detected in 2 of 29 children.Conclusion The detection rate of PKU in southern Xinjiang in recent 10 years was retrospectively analyzed.The mutation types and characteristics of exons 10,11 and 12 of PAH gene and the intron junction region of PAH gene in Xinjiang Uygur children with phenylketonuria were clarified,which laid the foundation for further study of phenylketonuria in Uygur families.

Objective To study the correlation between expression levels of serum Spexin and Pannexin 1 protein,glucose and lipid metabolism and insulin resistance in elderly patients with diabetic cataract.Methods A total of 118 elderly diabetic cataract patients were selected as the case group,and 103 elderly diabetic non-cataract patients were selected as the control group who were treated in the same hospital during the same period.Serum levels of Spexin and Pannexin1 were detected by enzyme-linked immunosorbent assay(ELISA).Fasting blood glucose(FPG)and glycosylated hemoglobin(HbA1c)were measured.Lipid metabolism related indicators including triacylglycerol(TG),high density lipoprotein cholesterol(HDL-C),total cholesterol(TC)and low density lipoprotein cholesterol(LDL-C)were detected in two groups of patients.Insulin resistance related indexes:fasting insulin(FINS),insulin sensitivity index(ISI),insulin resistance index(HOMA-IR)and islet beta cell function index(HOMA-β)were also detected.The correlation between serum Spexin and Pannexin1 levels,glucolipid metabolism and ISI was detected by Pearson method.Receiver operating characteristic(ROC)curves were used to assess the predictive value of serum Spexin and Pannexin1 levels and their combination in the development of cataract in elderly diabetic patients.Results The level of Spexin was lower in the observation group than that in the control group,and the level of Pannexin1 was higher than that in the control group(P＜0.01).Levels of TG,TC,LDL-C,FPG,HbA1c,FINS and HOMA-IR of the observation group increased compared with the control group,while HDL-C,ISI and HOMA-β levels decreased compared with the control group(P＜0.01).Pearson correlation analysis showed that serum Spexin level was positively correlated with ISI and HOMA-β,and negatively correlated with TG,TC,LDL-C,FPG,HbA1c,FINS and HOMA-IR in elderly patients with diabetic cataract(P＜0.05).Serum Pannexin1 was negatively correlated with ISI and HOMA-β,and positively correlated with TG,TC,LDL-C,FPG,HbA1c,FINS and HOMA-IR(P＜0.05).There was no correlation between the above indexes and HDL-C(P＞0.05).The combination of both serum Spexin and Pannexin1 predicted the development of cataracts in elderly diabetic patients was better than serum Spexin and Pannexin1 assessed individually(Z both combination-Spexin=3.220,P=0.001,Z both combination-Pannexin1=4.838,P＜0.001).Conclusion In elderly patients with diabetic cataract,the expression of serum Spexin decreases and the expression of Pannexin1 increases,and they have a certain correlation with glucose and lipid metabolism and insulin resistance