AIM:To investigate the preventive and therapeutic effects of sesamin(SES)on fatty liver disease in rats with hypertension combined with dyslipidemia,and to explore the potential mecha-nisms based on mRNA-seq.METHODS:Spontane-ously hypertensive rats(SHRs)were fed a high-fat,high-cholesterol diet to establish a rat model of hy-pertension combined with dyslipidemia,and then treated with SES for 16 weeks continuously.The ex-periment was divided into four groups:WKY,SHR,Model,and Model+SES(160 mg·kg-1·d-1).Blood pressure was measured using the tail-cuff method.Body weight was monitored,and body mass index was calculated.Liver morphology was detected by ultrasound,and liver thickness was measured.Liver wet weight was weighed,and liver index was calcu-lated.Liver volume was detected by the water dis-placement method.Serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT),aspartate amino-transferase(AST),and total bile acids(TBA)were de-tected by ELISA.Liver sequencing analysis was per-formed using mRNA-seq.Liver histomorphological changes were observed by HE staining.The degree of hepatic steatosis was observed by Oil Red O stain-ing,and the degree of hepatic fibrosis was observed by MASSON staining.The mRNA expression of Al-dh1a7,Nnmt,Irs2,Pltp,and Scd was detected by q-PCR.The protein expression of Scd,Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was detected by Western blotting.RESULTS:After 16 weeks of continuous SES administration to rats with hypertension combined with dyslipidemia,blood pressure was significantly reduced(P＜0.01),and body weight was decreased.Serum TG,TC,and LDL-C levels were decreased,while HDL-C levels were increased.Serum ALT and AST levels were decreased.Liver weight,organ in-dex,liver thickness,and liver volume were de-creased.The degree of hepatic steatosis and hepat-ic fibrosis was improved.A total of 545 differentially expressed mRNAs were identified in the livers of rats in each group,of which 278 were upregulated and 267 were downregulated.Among the 27 com-monly differentially expressed mRNAs,five mRNAs related to lipid metabolism were screened,namely Aldh1a7,Nnmt,Irs2,Pltp,and Scd.KEGG enrich-ment analysis showed that the enriched pathways were AMPK and PPAR.Further validation revealed that in the SES-treated group,the mRNA expression of Scd in the liver was decreased,while the mRNA expression of Nnmt was increased.The protein ex-pression of Scd was decreased,while the protein ex-pression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was increased.CONCLUSION:SES has preven-tive and therapeutic effects on fatty liver disease in rats with hypertension combined with dyslipidemia,and its mechanism of action may be related to the reduction of Scd expression levels in the liver and the increase in the expression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ.

AIM:To investigate the preventive and therapeutic effects of sesamin(SES)on fatty liver disease in rats with hypertension combined with dyslipidemia,and to explore the potential mecha-nisms based on mRNA-seq.METHODS:Spontane-ously hypertensive rats(SHRs)were fed a high-fat,high-cholesterol diet to establish a rat model of hy-pertension combined with dyslipidemia,and then treated with SES for 16 weeks continuously.The ex-periment was divided into four groups:WKY,SHR,Model,and Model+SES(160 mg·kg-1·d-1).Blood pressure was measured using the tail-cuff method.Body weight was monitored,and body mass index was calculated.Liver morphology was detected by ultrasound,and liver thickness was measured.Liver wet weight was weighed,and liver index was calcu-lated.Liver volume was detected by the water dis-placement method.Serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT),aspartate amino-transferase(AST),and total bile acids(TBA)were de-tected by ELISA.Liver sequencing analysis was per-formed using mRNA-seq.Liver histomorphological changes were observed by HE staining.The degree of hepatic steatosis was observed by Oil Red O stain-ing,and the degree of hepatic fibrosis was observed by MASSON staining.The mRNA expression of Al-dh1a7,Nnmt,Irs2,Pltp,and Scd was detected by q-PCR.The protein expression of Scd,Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was detected by Western blotting.RESULTS:After 16 weeks of continuous SES administration to rats with hypertension combined with dyslipidemia,blood pressure was significantly reduced(P＜0.01),and body weight was decreased.Serum TG,TC,and LDL-C levels were decreased,while HDL-C levels were increased.Serum ALT and AST levels were decreased.Liver weight,organ in-dex,liver thickness,and liver volume were de-creased.The degree of hepatic steatosis and hepat-ic fibrosis was improved.A total of 545 differentially expressed mRNAs were identified in the livers of rats in each group,of which 278 were upregulated and 267 were downregulated.Among the 27 com-monly differentially expressed mRNAs,five mRNAs related to lipid metabolism were screened,namely Aldh1a7,Nnmt,Irs2,Pltp,and Scd.KEGG enrich-ment analysis showed that the enriched pathways were AMPK and PPAR.Further validation revealed that in the SES-treated group,the mRNA expression of Scd in the liver was decreased,while the mRNA expression of Nnmt was increased.The protein ex-pression of Scd was decreased,while the protein ex-pression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was increased.CONCLUSION:SES has preven-tive and therapeutic effects on fatty liver disease in rats with hypertension combined with dyslipidemia,and its mechanism of action may be related to the reduction of Scd expression levels in the liver and the increase in the expression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ.

[Objective] To explore the expression of Nectin-4 in invasive bladder urothelial carcinoma (BUC) tissue and its clinical significance, so as to provide reference for clinical diagnosis and treatment of BUC. [Methods] Nectin-4 expression in 60 cases of invasive BUC and 40 cases of chronic inflammation of bladder mucosa was detected with immunohistochemical staining (IHC) and RNAscope.The results of the two methods were analyzed and compared, and the relationship between the two methods and the clinicopathological characteristics of invasive BUC was discussed.The correlation between the protein expression of Nectin-4 in BUC tissues, human epidermal growth factor receptor 2 (Her-2) and programmed death factor ligand 1 (PD-L1) was analyzed. [Results] The positive protein expression rates of Nectin-4 detected by IHC were 78.33%(47/60) and 17.50% (7/40) in the invasive BUC group and inflammatory group, respectively, while the positive mRNA expression rates of Nectin-4 detected by RNAscope were 83.33% (50/60) and 12.50% (5/40), respectively.The Kappa values of Nectin-4 in the invasive BUC group and inflammatory group were 0.732 and 0.610, respectively, with general consistency.The protein expression of Nectin-4 in invasive BUC was correlated with muscular invasion, histological grade, vascular thrombus, lymph node metastasis and clinical stage (P<0.05). The mRNA expression of Nectin-4 in invasive BUC was correlated with max tumor diameter, muscular invasion, histological grade, vascular thrombus, lymph node metastasis and clinical stage (P<0.05). The high expression of Nectin-4 in invasive BUC was positively correlated with the expression of Her-2 (P=0.002), but not with the expression of PD-L1 (P>0.05). [Conclusion] Nectin-4 is highly expressed in invasive BUC, and is usually associated with the pathological parameters of poor prognosis.Detection of Nectin-4 expression will help to guide clinical diagnosis and treatment.

Objective To investigate the clinical features and prognosis of hepatocellular carcinoma(HCC).Methods Medical records were collected from 850 HCC patients who were admitted to Hubei Provincial Hospital of Traditional Chinese Medicine from December 2014 to May 2022,and their clinical and prognostic features were analyzed.The chi-square test were used for comparison of categorical data between groups;the Kaplan-Meier method was used to calculate survival time and survival rate,and the log-rank test was used for comparison of survival time based on baseline features.Results Among the 850 HCC patients,male patients accounted for 82.6%,and the median age at initial diagnosis was 58.0(49.0,66.0)years,with the highest proportion of patients aged 50-69 years(59.8%).The patients with HBV infection accounted for the highest proportion of 77.4%;at initial diagnosis,49.2%of the patients had portal vein tumor thrombus,and 20.2%of the patients had extrahepatic metastasis,among which pulmonary metastasis accounted for the highest proportion of 44.2%(76/172).The patients with Barcelona Clinic Liver Cancer(BCLC)stage A(0),B,C,and D HCC accounted for 20.4%,22.5%,41.5%,and 15.6%,respectively.There was a significant difference in the distribution of BCLC stages between different groups based on sex(χ2=16.631,P=0.001),age(χ2=24.261,P=0.019),place of residence(χ2=39.776,P＜0.001),presence or absence of viral hepatitis(χ2=8.338,P=0.040),and presence or absence of regular antiviral therapy before initial diagnosis(χ2=26.140,P＜0.001).Follow-up was performed for 489 patients till death,with a median survival time of 19.99 months(95%confidence interval[CI]:14.86-25.12),and the 1-,3-,5-,and 10-year cumulative survival rates were 60.7%,39.9%,29.4%,and 22.7%,respectively.There was a significant difference in survival time between different groups based on age(χ2=13.452,P=0.009),history of viral hepatitis(χ2=6.123,P=0.013),regular antiviral therapy before initial diagnosis(χ2=15.505,P＜0.001),comorbidity with type 2 diabetes(χ2=9.820,P=0.002),the number of tumors(χ2=57.713,P＜0.001),maximum tumor diameter(χ2=41.862,P＜0.001),portal vein tumor thrombus(χ2=293.909,P＜0.001),extrahepatic metastasis at initial diagnosis(χ2=118.329,P＜0.001),BCLC stage(χ2=465.638,P＜0.001),surgical resection(χ2=78.86,P＜0.001),local treatment(χ2=36.216,P＜0.001),immune checkpoint inhibitor treatment and/or anti-tumor angiogenesis therapy(χ2=7.182,P=0.007),traditional Chinese medicine decoction treatment(χ2=30.050,P＜0.001),and comprehensive treatment regimens(χ2=13.221,P=0.004).Progression-free survival(PFS)was recorded for 259 patients(30.5%),with a median PFS of 10.98 months(95%CI:8.54-13.42).Conclusion HCC patients exhibit epidemiological characteristics in terms of sex,age,place of residence,presence or absence of viral hepatitis,regular antiviral therapy before initial diagnosis,tumor characteristics,treatment modality,and prognosis,with a low early detection rate and a short overall survival time,and therefore,it is urgent to perform early screening,early diagnosis,and early treatment.

OBJECTIVE To investigate the effect of a new variety of Sambucus williamsii Hance Yandan on the healing in rats with fractures.METHODS SD rats were randomly allocated to sham surgery group,model group,Zhonghua dieda pill group(0.54 g/kg),wild S.williamsii group(5.4 g/kg,using raw drug dosage),and high-,medium-,and low-dose groups of Yandan(10.8,5.4,2.7 g/kg,using raw drug dosage),with 12 rats in each group.Except for the sham surgery group,the remaining groups were prepared with a femoral fracture model.Starting from the second day after surgery,each group was intubated with the corresponding drugs and distilled water once daily for 8 consecutive weeks.At 2,4,and 8 weeks after administration,the levels of calcium,phosphorus,alkaline phosphatase(ALP),and osteocalcin(OCN)in rat serum were detected.Micro-CT scanning was used to evaluate the morphology and bone microstructural parameters of the fractured femur[bone mineral density(BMD),bone volume/tissue volume(BV/TV),trabecular number(Tb.N),trabecular separation(Tb.Sp),trabecular thickness(Tb.Th)],and hematoxylin-eosin staining was adopted to observe the morphological changes at the bone fracture site.RESULTS Compared with the model group,the levels of calcium in rat serum were significantly decreased(except at 4 weeks after administration),and the levels of phosphorus,ALP,and OCN were significantly increased(P＜0.05)at 2,4,and 8 weeks after administration in the high-dose group of Yandan;bone callus formation,connection of fracture ends,gradual blurring or disappearance of the fracture line,and opening of the marrow cavity were observed in the bone repair process,and a large amount of granulation tissue,fibroblasts,chondrocytes,new trabeculae,and new bone plates were visible at the fracture site of bone tissue;after 8 weeks of administration,BMD,BV/TV,Tb.N,and Tb.Th were significantly increased,and Tb.Sp was significantly decreased(P＜0.05).Most of the above indicators in the wild S.williamsii Hance group showed no significant changes.CONCLUSIONS Yandan has the effect of promoting fracture healing in rats,and its effect is superior to that of wild S.williamsii.

AIM: To observe the effect of metformin (Met) on the endothelial-mesenchymal transition (EMT) of rat alveolar epithelial type II cells and its mechanism. METHODS: The RLE-6TN cells were divided into 6 groups as follows: Control group; transforming growth factor-β

AIM: Sesamin (Ses) is one of the major lignans in sesame seeds with antihypertensive and antifibroticactivities, but its effect is weak. In this experiment, we combined vitamin E (VitE) and Ses to observe their effects on blood pressure and left ventricular fibrosis in spontaneously hypertensive rats (SHRs), and to explore its possible mechanism. METHODS: Male SHRs were randomly divided into SHRs+Ses+VitE group, SHRs+Ses group, SHRs+VitE group, and SHRs model group. Wistar-Kyoto (WKY) rats were setted as a normal control group. After 10 weeks of administration, systolic blood pressure (SBP) of rats was measured by tail cuff method, and the left ventricle was taken to calculate the organ index. Collagen deposition was observed by Masson staining, and cardiac collagen volume fraction (CVF) was analyzed. Expressions of collagen I, collagen III, transforming growth factor-β

Objective To compare the incidence rate of non-motor symptoms including constipation, depression,REM sleep disorder(RBD)in patients with Parkinson′s disease(PD)and essential tremor(ET). Methods Sixty patients with PD and 40 patients with ET treated in the department of neurology of Tianjin People′s Hospital from October 2015 to June 2016 were enrolled in the study.The clinical data were recorded.The incidence rates of constipation,depression,REM sleep disorder in PD patients and ET patients were compared in order to analyze the correlation among HY staging and the duration of constipation,depression and RBD in PD patients.Results The incidence rates of constipation,depression,REM sleep disorder in PD group were significantly higher than those in ET group(88.3%(53/60)vs.10.0%(4/40); 61.7%(37/60) vs.27.5%(11/40),51.7%(31/60)vs.7.5%(3/40)),the differences were statistically significant(χ2=60.08,11.22,20.86,P<0.05).Spearman rank correlation analysis showed that the HY staging of patients with PD was related to the duration of constipation,the duration of depression and the duration of RBD(r=0.570,0.369,0.439,P<0.01).Conclusion The degree of correlation between constipation and HY staging is relatively high in PD patients.PD patients with constipation,depression,REM sleep disorder can provide reference for early diagnosis and differential diagnosis of ET patients.

Objective To investigate the prevalence of DUOX2 mutations in Chinese patients with congenital hypothyroidism (CH) and to discuss the inheritance pattern of DUOX2 gene.Methods Blood samples were collected from 91 CH children and their genomic DNA was extracted from peripheral blood leukocytes.All exons and exon-intron boundaries of DUOX2 were analyzed by target next-generation sequencing and family trios was established to study the inheritance pattern of DUOX2 gene.Results Fifty-four out of 91 children with CH carried DUOX2 mutation, with a prevalence of 59.34%.Of the 54 CH children, 36 carried DUOX2 biallelic mutations.In all 12 family trios with probands carrying biallelic DUOX2 mutations, the parents carried heterozygous DUOX2 mutations while still showing normal thyroid function, suggesting that CH caused by DUOX2 mutations is inherited in an autosomal recessive manner.Conclusion DUOX2 gene is one of the most frequently mutated genes in Chinese CH patients and its inheritance pattern is an autosomal recessive one.

OBJECTIVE: To investigate the effect of cerebral hemodynamic changes on white matter damage in premature infant with patent ductus arteriosus(PDA). METHODS: A total of 106 premature infants were enrolled in the study, including 35 PDA infants with hemodynamic changes (hsPDA group), 35 PDA infants without hemodynamic changes (non-hsPDA group) and 36 non-PDA infants (control group). Serum level of neuron-specific enolase (NES) was detected and craniocerebral ultrasound examination was performed on d3, d7 and d14 after birth. The correlation between blood flow rate of PDA and gray scale value of lateral ventricle was analyzed. RESULTS: Gray scale values of lateral ventricle and serum levels of NES in hsPDA group were higher than those in control group on d3, d7 and d14 (P<0.01), but no significant difference was observed between non-hsPDA group and control group (P>0.05). There was a positive correlation between the blood flow rate of PDA and gray scale value of lateral ventricle (r=0.876, P<0.01) in premature infants. CONCLUSION Patent ductus arteriosus with hemodynamic changes is closely related to white matter damage in premature infants, and early intervention is necessary.
Ductus Arteriosus, Patent ; complications ; Hemodynamics ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Ultrasonography ; White Matter ; pathology