Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

BACKGROUND:The guinea pig is considered to be the most useful spontaneous model for evaluating primary osteoarthritis in humans because of its similar knee joint structure and close histopathologic features to those of humans. OBJECTIVE:To investigate the pathological process of spontaneous knee osteoarthritis in guinea pigs by analyzing the histopathology of the total knee joint of guinea pigs aged 1 to 18 months. METHODS:Eight healthy female Hartley guinea pigs in each age group of 1,6,10,14,16,and 18 months old were selected.The quadriceps femoris was taken for hematoxylin-eosin staining,and the total knee joint was stained with hematoxylin-eosin and toluidine blue.The histopathology of the cartilage,subchondral bone,synovium,meniscus,and muscles were observed under light microscope.Mankin's score and synovitis score were compared,and the correlation analysis was conducted. RESULTS AND CONCLUSION:As the guinea pig age increased,the Mankin's score increased(P<0.05),and the pathological score of synovitis also gradually increased(P<0.05),and there was a significant positive correlation between the two(r=0.641,P<0.001).The incidence rate of subchondral bone marrow lesion in 18-month-old guinea pigs was 50%,and the incidence of meniscus injury was 37.5%.In addition,osteophyte and narrowing of the joint space were observed,and only a few guinea pigs had inflammation in the quadriceps femoris.To conclude,guinea pigs develop significant cartilage defects,synovial inflammation,subchondral bone lesions,meniscus injury,osteophyte formation,and joint space narrowing as they age,all of which are similar to the pathological processes of primary knee osteoarthritis in humans,making it an ideal model of spontaneous knee osteoarthritis.

Chronic kidney disease(CKD)is a chronic renal structural and functional disorder caused by multiple causes(history of kidney injury>3 months),with complex etiology and high inci-dence,which will eventually lead to end-stage re-nal disease(ESRD).Common chronic kidney diseas-es include diabetic nephropathy,polycystic ne-phropathy,nephrogenic diabetes insipidus and re-nal fibrosis.At present,there is still a lack of effec-tive specific treatment for chronic kidney disease.The Apelin system is an endogenous physiological regulator.Studies have shown that Apelin is in-volved in the occurrence and development of the above diseases mainly through the regulation of kidney body fluids and blood vessels,and the regu-lation of kidney glucose and lipid metabolism and immunity.This article aims to review the role of Apelin in chronic kidney diseases in recent years,and provide ideas for the treatment and drug de-velopment of kidney diseases with Apelin as a new target.

[Purpose]To analyze the cost-effectiveness of endoscopic screening for upper gastroin-testinal cancer in Yangcheng County of Shanxi Province.[Methods]People aged from 40 to 69 who participated in upper gastrointestinal cancer screening in Yangcheng County in 2018 were se-lected as the study subjects to participate in upper gastrointestinal cancer screening in 2018,and endoscopic examination with iodine staining and indicative biopsy were performed for screening.The detection rates of precancerous lesions and upper gastrointestinal malignancies,and early di-agnosis rates were calculated,and compared among different groups.The data of screening cost were collected;and the per capita screening cost,the average cost of early case detection and ear-ly detection cost index(EDCI)were calculated.[Results]Among 2 950 subjects undergoing en-doscopy,pathological biopsy was completed in 2 073 cases(70.27％),374 cases of precancerous le-sions(12.68％)and 52 cases of malignancies(1.76％)were detected,among which 17 cases were up-per gastrointestinal cancer with a detection rate of 0.58％,there were 44 early cases with an early diagnosis rate of 84.62％.The detection rate of precancerous lesions and positive cases in men was higher than that of women,but the early diagnosis rate of upper gastrointestinal cancer was lower than that of women;the detection rate of positive cases and digestive tract cancer of 50 years and above were higher than those of people aged 40 to 49.The cost of screening for one positive lesion was 25 528.85 CNY,the cost of screening for one early case was 30 170.46 CNY.The EDCI was 0.52,indicating a good cost-effective value.[Conclusion]The study shows that the early diagnosis and early treatment screening program of upper gastrointestinal cancer has achieved remarkable re-sults in Yangcheng County.The follow-up screening work should focus on men and people over 50 years old,and strengthen the publicity of upper gastrointestinal screening for cancer.

Aim To establish and evaluate an alternative meth-od for detecting skin sensitization of cosmetics based on local lymph node assay using bromodeoxyuridine(BrdU)with flow cytometry(FCM).Methods(1)25％hexyl cinnamic alde-hyde(HCA)was chosen as a positive control with an acetone:olive oil(4∶1,V/V,AOO)mixture as a vehicle control for the experiment.The dorsal sides of both ears of mice were treated with test solutions on day 1,day 2,and day 3.Brdu solution was injected inter-peritoneally on day 5.On day 6,the bilateral ears and mandibular lymph nodes were excised,and the number of Brdu positive cells was measured by flow cytometry.The stim-ulation index(SI)was calculated to identify whether it was ≥3,in order to establish the method of LLNA:Brdu-FCM.(2)BrdU-FCM test was conducted using a blind method with the fif-teen reference substances listed in OECD TG429 whose skin sensitization potentials were known.The test substances were dissolved in AOO,N,N-dimethylformamide(DMF)or dimeth-yl sulfoxide(DMSO)at three different concentrations.Tests were performed the same as above.SI and EC2.7 were calculat-ed to evaluate whether the test substance was categorized as a skin sensitizer.The reliability and accuracy of the method were validated by comparing the classification of test substances with that in OECD TG429.Results The SI for 25％HCA was 3.9,showing positive in the skin sensitization test.It demonstrated that the LLNA:Brdu-FCM test method was properly implemen-ted.Nine test substances(2,4-dinitrochlorobenzene,4-pheny-lenediamine,cobalt chloride,2-mercaptobenzothiazole,hexyl-cinnamaldehyde,eugenol,phenyl benzoate,cinnamic alcohol,imidazolidinyl urea)were positive,and six test substances(methyl methacrylate,chlorobenzene,isopropanol,lactic acid,methyl salicylate,salicylic acid)were negative.The method was evaluated with sensitivity of 90％,specificity of 100％,positive prediction rate of 100％,negative prediction rate of 83％,false positive rate of 0％,false negative rate of 17％and accuracy of 93％.The LLNA:BrdU-FCM assay could correctly categorize the test substances that were skin sensitizers or non-sensitizers.Conclusion The LLNA:BrdU-FCM assay appears to be a relia-ble predictor of skin sensitization protential of chemicals,and it is expected to an alternative method for identifying skin sensitization as a supplementary in safety evaluation of cosmetic ingredient.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Objective To establish an inductively coupled plasma-mass spectrometry(ICP-MS)method for the analysis of 29 mineral elements in Artemisiae Argyi Folium(AAF),and to develop a model for judging the origin of AAF based on the elemental fingerprint combined with chemometrics.Methods The variance method was used to compare the contents of 29 mineral elements in AAF samples from Qichun of Hubei province,Hebei province and Henan province,respectively.The discriminant models of AAF from different habitats were established by discriminant analysis,PLS-DA and PCA-Logistic regression algorithms.Results The differences of the 22 elements(V,Cr,Ni,As,Se,Rb,Mo,Cd,Sb,Ba,Hg,Pb,K,Li,B,Mg,Al,P,Ca,Fe,Zn,and Ga)in samples from Qichun of Hubei province,Hebei province and Henan province are extremely significant(P＜0.01).The discriminant analysis model showed that eight kinds of element variables(P,Cr,K,Li,Hg,Ba,Mg,and Mo),which have a significant effect on the origin discrimination are gradually introduced into the discriminant model,and the correct rate of back test is 100％.The correct rate of"leave one method"cross-validation is 96.7％.The PLS-DA model showed good prediction ability,and the variable importance projection values of K,P and Mg elements were greater than one,which could be used as the difference marker of AAF from different habitats.The accuracy of the origin discrimination model constructed by PC A-Logistic regression analysis was 100％.The elements with high first principal component loadings were Li,B,Mg,Al,P,K,Ca,V,Cr,Fe,Ni,Zn,As,Rb,Cd,Sb,and Ba.Conclusion This study shows that elemental fingerprint technology combined with chemometric analysis can identify AAF from Qichun of Hubei province,Hebei province,or Henan,providing technical support for the traceability of the origin of Artemisia argyi.

Objective This study sought to establish a non-alcoholic fatty liver disease(NAFLD)model in Wistar-SD hypercholesterolemia(WSHc)rats induced by a high-fat diet and to reveal the pathogenesis of NAFLD in these rats through the Srebp-1 gene.Methods After 2 weeks of dietary treatment,thirty 6-week-old WSHc rats were divided into High-fat control group,HFD+AAV no load group,and HFD+AAV group,with 10 rats in each group.The HFD+AAV no load group and HFD+AAV group were intravenously injected with a vector virus and an shRNA-containing virus,respectively.WSHc rats were fed with a normal fat diet as a normal control group.Serum levels of ALT,AST,TBIL,ALP,TBA,GLU,CHOL,and TG were measured every 2 weeks.After a further 8 weeks of feeding,the rats were euthanized and livers were excised for HE staining,Oil Red O staining,Masson staining,and Sirius red staining to observe the morphology,lipid deposition,and fibrosis of the liver tissues.RT-qPCR was performed to detect the expression of lipid metabolism-related genes namely Srebp-1,Aacs,FASN and LDLR in the livers.Furthermore,hepatocytes were isolated,cultured,and divided into a normal control group and a high-fat control group.Next,expression of the Srebp-1 gene was detected by RT-qPCR.Srebp-1 knockout(KO)hepatocytes were constructed,then TG content was detected and the lipid accumulation was observed by Oil Red O staining.Results After 10 weeks of high-fat diet treatment,serum ALT(P＜0.001),ALP(P＜0.001),TBA(P＜0.05),GLU(P＜0.001),and CHOL(P＜0.001)significantly increased in WSHc rats.Abnormal lipid deposition with formation of large vacuolar lipid droplets and fibrotic lesions in livers were observed.The mRNA expression of Srebp-1 noticeably increased in WSHc rats(P＜0.001).Moreover,compared with the high-fat control group,the ALT(P＜0.05)and GLU(P＜0.01)in the HFD+AAV group decreased,and liver lipid deposition and the formation of large vacuolar lipid droplets were alleviated.Expressions of genes such as FASN(P＜0.05)and LDLR(P＜0.01)were significantly upregulated.Additionally,there was a significant increase in the expression of Srebp-1 in hepatocytes of the high-fat control group(P＜0.001),while after Srebp-1 gene knockout,cellular TG levels decreased and the degree of lipid droplet aggregation was reduced.Conclusions The Srebp-1 gene plays a regulatory role in hepatic lipid metabolism and deposition,modulating the expression of lipid metabolism-related genes in WSHc rats with NAFLD.In vitro experiments demonstrated that downregulation of Srebp-1 alleviates lipotoxic injury in hepatocytes,suggesting that the development of NAFLD in WSHc rats is closely associated with abnormally high expressions of the Srebp-1 gene.

OBJECTIVE To observe the effect of acupuncture combined with a modified Zhengan Xifeng Decoction on the early clinical symptoms and oxidative stress status of patients with hypertensive intracerebral hemorrhage(HICH)of liver-kidney yin defi-ciency syndrome.METHODS A total of 60 patients with hypertensive intracerebral hemorrhage(liver-kidney yin deficiency syn-drome)who successfully received 24-hour acute-phase treatment at the Department of Neurosurgery,Acupuncture and Rehabilitation Department,and wards of Kunshan Hospital Affiliated to Nanjing University of Chinese Medicine(Kunshan Traditional Chinese Medi-cine Hospital)from July 2021 to January 2023 were recruited.A randomization table generated by SPSS 22.0 software was used to di-vide the patients into a control group and an observation group,with 30 patients in each group.The control group received symptomatic treatment,conventional rehabilitation training,and modified Zhengan Xifeng Decoction,while the observation group received additional acupuncture treatment on the basis of the control group.The treatment course was 1 month for both groups.Clinical effective rate,TCM syndrome scores,motor and neurological function scores[Activity of Daily Living(ADL)scale,National Institutes of Health Stroke Scale(NIHSS),Modified Ashworth Scale(MAS),Simplified Fugl-Meyer Assessment(FMA)scale],improvement in hematoma lesions,Fraction anisotropy(FA)ratio(rFA),and serum levels of antioxidant stress response factors Kelch-like ECH-associated protein 1(Keap1)and nuclear factor-E2-related factor 2(Nrf2)were observed before and after treatment in both groups.RESULTS After treat-ment,the clinical effective rate in the observation group was significantly higher than that in the control group(P<0.05);the TCM syn-drome scores in both groups decreased significantly(P<0.05),with the observation group showing better results than the control group(P<0.05);the ADL and FMA scores in both groups reduced significantly(P<0.05,P<0.01),while the NIHSS and Ashworth Scale scores increased significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);serum Keap1 levels decreased significantly in both groups(P<0.01),while Nrf2 levels enhanced significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);imaging studies showed that after treat-ment,the residual hematoma volume decreased significantly in both groups(P<0.05,P<0.01),and the rFA value increased signifi-cantly(P<0.05,P<0.01),with the observation group showing better results than the control group(P<0.01).CONCLUSION On the basis of standard treatment for the acute phase,acupuncture combined with Zhengan Xifeng Decoction can significantly improve the early clinical symptoms of HICH patients with liver-kidney yin deficiency,reduce oxidative stress levels,and promote the recovery of nerve and motor functions.

Objective:To establish a digital quality evaluation system for Salvia miltiorrhiza-Monascus fermentation products,screen critical quality markers,and provide methodological support for their intelligent quality control.Methods:Ultra-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry(UPLC-Q-Orbitrap-MS)was employed to quantitatively analyze 34 bioactive components(e.g.,tanshinone Ⅱ A and alvianol-ic acid B)in 20 batches of fermentation products.The key markers were screened through hierarchical cluster anal-ysis and partial least squares discriminant analysis,and an intelligent discriminant model was constructed with sup-port vector machine machine learning algorithm to digitally analyze the characteristics of quality differences between batches.Results:Thirty-four common peaks were calibrated across all batches.Combined with partial least squares analysis,six key difference markers were further screened,including terpenoids such as isotanshinone Ⅱ A and tan-shinone Ⅱ A and phenolic acids such as salvianolic acid G.The support vector machine model can achieve 100％accuracy of origin discrimination by optimizing parameters jointly with genetic algorithm and grid search.Conclusion:This study developed a digital quality evaluation system for Salvia miltiorrhiza-Monascus fermentation products through a three-step analytical strategy("chemical feature exploration-marker screening-model valida-tion"),providing a transferable technical pathway for the intelligent transformation of traditional Chinese medicine quality control.