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 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 investigate the population distribution of non-alcoholic fatty liver disease before and after renaming and the association between the types of metabolic risk factors(MRF)for metabolic dysfunction-associated steatotic liver disease(MASLD)and advanced liver fibrosis.Methods This study was conducted among 515 patients who were admitted to The Affiliated Hospital of Xuzhou Medical University and Wuxi Fifth People's Hospital from January 2019 to January 2022 and had hepatocyte steatosis≥5%by liver biopsy.Among these patients,2 patients did not meet the diagnostic criteria for nonalcoholic fatty liver disease(NAFLD)and metabolic associated fatty liver disease(MAFLD),respectively,and were classified as steatotic liver disease(SLD)with other specific causes,and the other 513 patients were divided into MASLD group with 275 patients,comorbid group with 216 patients(MASLD comorbid with other liver diseases),and cryptogenic SLD group with 22 patients.The above groups were compared in terms of clinical features,laboratory markers,and advanced liver fibrosis.The MASLD patients with different types of MRF were compared in terms of clinical features,laboratory markers,and advanced liver fibrosis,and the risk factors for advanced liver fibrosis in patients with MASLD were analyzed.The Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups and further comparison between two groups;the chi-square test was used for comparison of categorical data between multiple groups,and Bonferroni correction was used for further comparison between two groups.The logistic regression analysis was used to identify the risk factors for liver fibrosis.Results Among the 515 patients with SLD,297 patients(57.7%)met the diagnostic criteria for NAFLD,among whom 22 were classified as cryptogenic SLD and 275 met the diagnostic criteria for MASLD,and 467(90.7%)were diagnosed with MAFLD.There were significant differences between the three groups in sex,body mass index(BMI),gamma-glutamyl transpeptidase,triglyceride,cholesterol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,fasting plasma glucose,NAFLD fibrosis score(NFS),fibrosis-4(FIB-4),and F3-4(all P＜0.05).Compared with the MASLD group and the cryptogenic SLD group,the comorbid group had the highest proportion of patients with advanced liver fibrosis(P＜0.001).With the increase in the type of MRF,the patients tended to have an older age,a significantly higher proportion of female patients,a higher possibility of hypertension and diabetes,and higher levels of metabolic parameters including BMI,blood lipids,and blood glucose(all P＜0.05).With the increase in the types of MRF in MASLD patients,they tended to have significantly higher noninvasive fibrosis scores(NFS and FIB-4)and a significantly higher proportion of patients with advanced liver fibrosis(P＜0.05).The multivariate logistic regression analysis showed that age≥50 years(odds ratio[OR]=2.622,95%confidence interval[CI]:1.091-6.300,P=0.031)and the increase in the type of MRF(OR=1.876,95%CI:1.194-2.947,P=0.006)were independent risk factors for MASLD with severe liver fibrosis.Conclusion The new definition of MASLD is based on the positive identification of MRF,and the reclassified population of MASLD is smaller than that of MAFLD,with little difference from that of NAFLD.In addition,age≥50 years and the increase in the type of MRF are independent risk factors for MASLD with advanced liver fibrosis.

In the field of biomedicine,two-dimensional(2D)cell lines and animal models have played an im-portant role in the study of cell pathways and drug targets.However,due to species differences between humans and other animals,and the lack of hierarchy,cellular diversity,and cell-cell or cell-matrix interactions,2D cell lines could not ful-ly reflect what cells actually look like in the human body.Organoids are three-dimensional(3D)in vitro culture models de-rived from autologous tissue stem cells,which make up for the defects of 2D culture and can simulate the structure and function of real human organs to a certain extent,providing new ideas for disease diagnosis and treatment.Among them,lung organoids(LO)are a typical case studying the development process of human lung and the generation principle of lung diseases.Relevant studies have provided help for the treatment of pulmonary fibrosis,lung cancer,lung injury and other diseases.This paper aims to summarize and analyze the research progress of lung organoids in recent years,and fur-ther summarize the application of LO in the diagnosis and treatment of lung diseases.

Objective:To investigate the effects of chest pain center construction in basic-level hospitals on treatment time and short-term prognosis in patients with acute ST-elevation myocardial infarction.Methods:A total of 162 patients with acute ST-elevation myocardial infarction who received percutaneous coronary intervention (PCI) in The First People's Hospital of Jiande between November 2014 and November 2018 were included in this study. Among them, 66 patients who received treatment in The First People's Hospital of Jiande between November 2014 and October 2016 were included in the control group. The remaining 96 patients who received treatment between November 2016 and November 2018 were included in the study group. The underlying diseases, PCI success rate, first medical contact-to-balloon time, door-to-balloon time, in-hospital mortality, incidence of heart failure on the next day of PCI, length of hospital stay, hospital medical cost were retrospectively analyzed.Results:There were no significant differences in underlying disease composition ratio and PCI success rate between the two groups (both P > 0.05). There were significant differences in first medical contact-to-balloon time [(185.2 ± 53.7) minutes vs. (108.6 ± 46.4) minutes, t = 6.128], door-to-balloon time [(121.5 ± 23.2) minutes vs. (68.7 ± 14.3) minutes, t = 7.341], length of hospital stay [(10.3 ± 3.5) days vs. (7.2 ± 2.8) days, t = 5.128], hospital medical cost [(43 582.0 ± 7 186.5) yuan vs. (35 479.0 ± 4 213.1) yuan, t = 8.361], in-hospital mortality [6.1% vs. 3.1%, χ2 = 4.784], the incidence of heart failure on the next day of PCI [13.6% vs. 4.2%, χ2 = 8.253] between the control and study groups (all P < 0.05). Conclusion:Establishment of a standardized chest pain center construction in basic-level hospital can greatly shorten the first medical contact-to-balloon time, door-to-balloon time and length of hospital stay, improve the cardiac function and prognosis of patients with myocardial infarction, and reduce medical cost.

As an immune complex-mediated renal disease, membranous nephropathy(MN) can occur at all ages.Primary membranous nephropathy(PMN) can lead to end-stage renal disease although it is not common in children.Antibodies against M-type phospholipase A2 receptor / thrombospondin type-1 domain-containing 7A are initially detected in adult PMN, and also present in children and adolescents with PMN.These antibodies serve as useful biomarkers to diagnose and monitor PMN.Rituximab has been successfully used in the treatment of adult PMN, and is possibly effective in children with PMN as well.

Objective To explore the prognostic values of telomerase reverse transcriptase promoter (TERTp) mutation and 1p/19q co-deletion in newly-diagnosed O6-methylguanine-DNA methyltransferase (MGMT) promoter un-methylated/isocitrate dehydrogenase (IDH) wild-type glioblastoma multiform (GBM). Methods A total of 82 patients pathologically newly-diagnosed MGMT promoter un-methylated/IDH wild-type GBM, admitted to our hospitals from March 2016 to November 2018, were included in this study. TERTp mutations (TERTp wild-type and TERTp mutation [C228 mutation and C250 mutation]) in GBM specimens were detected by PCR sequencing, 1p/19q co-deletion in GBM specimens was detected by fluorescence in situ hybridization (FISH), and clinical data, adverse reactions and prognoses of patients with different molecular typing were compared. Results There were 33 patients in the TERTp wild type group with mean age of 48 years, and 49 patients in the TERTp mutation group with mean age of 59 years; the difference of age was significant (P<0.05); there were no statistical differences in gender distribution, Karnofsky performance status (KPS) scores, tumor sites and surgical resection degrees between the two groups (P>0.05). There were 8 patients with 1p/19q co-deletion and 74 patients without 1p/19q co-deletion; no significant differences in above clinical parameters were noted between the two groups. There were no statistically significant differences in the incidences of bone marrow suppression, digestive tract response and fatigue, disease progression rate, or survival rate between patients from TERTp wild type group and TERTp mutation group, and between patients with 1p/19q co-deletion and patients without 1p/19q co-deletion (P>0.05). No significant differences in above clinical parameters, disease progression rate, and survival rate were noted between patients with C228 mutation and C250 mutation (P>0.05). Conclusion TERTp typing and 1p/19q co-deletion status do not have prognostic value in newly-diagnosed MGMT un-methylated/IDH wild-type GBM patients; patients with TERTp mutations have older age than wild-type patients; patients with C250 mutation trend to have higher survival rate than those with C228 mutation.

OBJECTIVE: To analyze the clinical characteristics of atypical occupational chronic mercury poisoning cases and explore ways to avoid misdiagnosis. METHODS: The clinical data of 2 atypical occupational chronic mercury poisoning cases were retrospectively analyzed. RESULTS: The two cases were in the same instrument factory. They were engaged in the inspection and filling of thermometers, with a long history of occupational mercury exposure. The main clinical manifestations were the nervous system damage. In the two cases,one case showed severe pain in limbs and joints accompanied with neurasthenia syndrome, oral-gingivitis and increased urine mercury; while the other one showed Parkinson's syndrome-like involuntary tremor whenever at rest or activity accompanied with neurasthenic syndrome and increased urine mercury,without oral-gingivitis. The physical examination showed notable finger tremor,tongue tremor,and eyelid tremor,and one case had coarse tremor of upper limb. Both cases were diagnosed as occupational chronic mercury poisoning. CONCLUSION: The nervous system is the most common site of involvement of patients with occupational chronic mercury poisoning,whose clinical manifestations are diverse. Clinicians should raise awareness of mercury poisoning,consult medical history in detail and reduce misdiagnosis.