OBJECTIVETo observe the effect of Zhenqing Recipe (ZQR) on non-alcoholic fatty liver (NAFL), and the expression of hepatic salt-inducible kinase 1 (SIK1) and sterol-regulatory element binding protein-ic (SREBP-lc) in type 2 diabetes rats.

METHODSA rat model of type 2 diabetes was established by high fat/sucrose diet combined with intraperitoneal injection of small dose streptozotocin (STZ) . Modeled rats were randomly divided into the model group, the ZQR group, and the metformin group, 8 in each group. Eight rats were recruited as a normal control group. ZQR at the daily dose of 12 g crude drugs/kg was administered to rats in the ZQR group by gastrogavage. Metformin suspension at the daily dose of 150 mg/kg was administered to rats in the metformin group by gastrogavage. Equal volume of distilled water was administered to rats in the normal control group and the model group. All medication lasted for 12 weeks. The levels of fasting blood glucose (FBG), free fatty acid (FFA), serum triglyceride (TG), serum total cholesterol (TC), serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were detected. The body weight and wet liver weight were weighed, and the liver weight index calculated. The liver TG content was measured. The pathological changes of liver and the expression of SIK1 were observed by HE staining and immunohistochemistry. The mRNA and protein expression of SIK1 and SREBP-1c were detected using RT-PCR and Western blot.

RESULTSCompared with the normal control group, FBG, FFA, TG, TC, ALT, AST, liver weight index, and liver TG contents significantly increased (P < 0.01); liver steatosis was severe, the mRNA and protein expression of SIK1 obviously decreased (P < 0.01); mRNA and protein expression of SREBP-1c increased (P < 0.01). After drug therapy, compared with the model group, FBG, FFA, TG, TC, ALT, AST, and liver weight index significantly decreased, liver TG contents significantly decreased, the mRNA and protein expression of SIK1 obviously increased, while mRNA and protein expression of SREBP-1c obviously decreased (P < 0.05, P < 0.01) in the ZQR group and the metformin group (P < 0.05, P < 0.01); and the pathological changes were also improved. All the indices were improved more in the ZQR group (all P < 0.05).

CONCLUSIONIn this experiment, we found that the expression of SIK1 decreased in NAFL rats with type 2 diabetes. ZQR could alleviate lesion of NAFL type 2 diabetes rats possibly by up-regulating hepatic SIK1 expression at mRNA and protein levels.

Animals ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Fatty Liver ; complications ; drug therapy ; metabolism ; Liver ; metabolism ; Male ; Protein-Serine-Threonine Kinases ; metabolism ; Rats ; Rats, Wistar ; Sterol Regulatory Element Binding Protein 1 ; metabolism

Biomedical Research ; China ; Preventive Medicine ; Research Support as Topic

Biomedical Research ; China ; Preventive Medicine ; Research Support as Topic

To observe different expression patterns of β-catenin and its clinical significance in colorectal cancer (CRC).Methods A total of 181 cases of CRC tissues and 30 cases of normal colorectal tissue were investigated by immunohistochemistry for the expression of β-catenin.Results The expression rate of β-catenin was 56.9％ (103/181) in CRC,and higher than that in normal colorectal tissue (P ＜ 0.05).The overexpression of nuclear β-catenin was significantly correlated with histological differentiation,lymph node metastasis and Dukes' stage in CRC (P ＜ 0.05),and no relationship with other pathological parameters,such as age,gender and the depth of infiltration.The incomplete membranous expression of β-catenin was significantly correlated with histological differentiation,the depth of infiltration,lymph node metastasis and Dukes' stage in CRC (P ＜ 0.05).The high expression of nuclear β-catenin related to histological differentiation and Dukes' stage in CRC (P ＜ 0.05).In the follow-up data of 82 cases of CRC,the expression of nuclear β-catenin was associated with poor prognosis,and the 5-year survival rate was significantly lower than that of self-control groups (P ＜ 0.05).Conclusion β-catenin plays important roles in colorectal carcinogenesis.Abnormal expression of β-catenin was related to the aggressive progression of CRC and may be helpful for evaluating the prognosis of patients with CRC.β-catenin is expected to become a new target for diagnosis and treatment of CRC in future.

Objective To identify gene mutations in two families with epidermolytic hyperkeratosis (EHK).Methods Clinical data were collected from two families with EHK.Peripheral blood was isolated from the probands and unaffected family members in the families as well as from 50 healthy controls.PCR was performed to amplify the encoding exons and flanking intron regions of KRT1 and KRT10 genes followed by direct DNA sequencing.Results Two mutations in the KRT10 gene,including a heterozygous acceptor splice site mutation in intron 4 (c.1030-2 A＞G) and a heterozygous missense mutation c.467 G＞A,were identified in the probands of both families,but absent in the unaffected family members or healthy controls.ConclusionThe splice site mutation c.1030-2 A＞G and missense mutation c.467 G＞A might be responsible for the phenotype of EHK in the two families.

Objective To investigate the relationship between chromosome 6p copy number alterations (CNAs) and postoperative intrahepatic recurrence of hepatocellular carcinoma (HCC);and to screen for the target genes in CNA(s).Methods Array comparative genomic hybridization (CGH) and expression arrays were used to detect CNAs and differences in gene expression, respectively.The associations between CNAs in 6p and HCC recurrence were analyzed using the log-rank test, the Kaplan-Meier curves and the Cox proportional hazards models on 66 patients who had been follow-up for 2.6 ～ 73.3 months.The differentially expression of genes in the potentially recurrence-related CNAs were further evaluated by the MannWhitney U test on 117 HCCs, which included 109 cases with paired array CGH and expression data.Results 6p CNAs were detected in 46 (69.7％) of the 66 HCCs.Of the 8 CNAs with the most frequent recurrence of over 20％ , a gain at 6p21.1 was independently associated with a 2.3-fold (95％ CI =1.1 ～ 5.1, P ＜ 0.05) increased risk for intrahepatic recurrence and with a more pronounced 3.3-fold (95％ CI =1.4 ～ 8.2, P ＜0.05) risk for early recurrence (≤ 1 year).A panel of 9 genes, including BYSL and RPL7L1 within the documented 6p21.1, were observed to be upregulated in HCCs with 6p21.1 gain when compared with HCCs without (all P ＜ 0.05).A high BYSL expression significantly correlated with a larger tumor size (＞ 6 cm), vascular invasion and advanced tumor stage (all P ＜ 0.05), and high RPL7L1 expression significantly correlated with vascular invasion and advanced tumor stage (all P ＜ 0.05).Conclusion A gain at 6p21.1 was an independently prognostic marker for intrahepatic recurrence of postoperative HCC, particular for early recurrence, and BYSL and RPL7L1 might be the target genes in the recurrence-related 6p21.1 gain.

Dengzhan Shengmai capsule, as a compound Chinese patent medicine, consists of four herbs: Herba Erigerontis, Ginseng, Ophiopogon, and Schisandrae Chinensis Fructus, and contains significant components of flavonoids, lignans, saponins, and organic acids. It is widely used clinically to treat cerebrovascular diseases such as chronic cerebral hypoperfusion and dementia with remarkable efficacy. This study proposes a research strategy for multi-component traditional Chinese medicine metabolites based on prediction databases and unfolds the analysis using Dengzhan Shengmai capsule as an example. Using the UPLC-Q-TOF/MS method, the analytical method was established and detected biological samples such as urine, feces, and bile of rats before and after administration based on the prediction of theoretical metabolites of Dengzhan Shengmai capsule. The possible secondary fragment ion information of metabolites was identified by comparing the detected results with prediction databases. The metabolites were identified based on the archetypal component mass spectrometric cleavage law and multistage mass spectrometric data. 51 metabolites, mainly flavonoid, organic acid, and lignan constituents, were finally identified from rat biosamples based on 306 theoretical metabolites of Dengzhan Shengmai capsule. This study provides a new strategy for the identification of metabolites in vivo and the analysis of metabolic pathways of TCM. The study complied with the procedures established by the Animal Experiment Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and passed the animal experiment ethics examine (No. 00003645).

The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an inhibitory receptor mainly expressed on active T-cells, or natural killer cells (NK cells) that activate negative stimulus signals in immune cells by combining with multiple ligands on the surface of target cells including tumor cells and infected cells. TIGIT plays an important regulatory role in the immune pathogenesis of tumors, viral infections and various autoimmune diseases by inhibiting the over activation of cells and the over secretion of proinflammatory cytokines. Recent researches show that TIGIT is highly expressed in T cells and NK cells of cancer patients, and is related to disease progression and poor clinical prognosis. Researchers try to enhance the activity of T cells or NK cells by blocking the binding of TIGIT and its ligand for therapeutic intervention. At present, there have been many reports about the use of anti-TIGIT monoclonal antibody treatment in different mouse tumor models leading to tumor regression, TIGIT has received extensive attention in cancer immunotherapy as a promising target for next generation cancer immunotherapy. Several clinical trials are currently evaluating the efficacy of anti-TIGIT monoclonal antibodies (mAbs) in patients with several cancers. The most advanced candidate, tiragolumab, has exhibited remarkable efficacy in programmed cell death ligand 1 (PD-L1)-positive non-small cell lung carcinoma (NSCLC) patients in phase Ⅱ clinical trials, in combination with PD-L1 blockade. However, the specific mechanism of TIGIT blockade remains to be fully elucidated.

Objective To explore the ameliorative effects of standardized tertiary rehabilitation(STR)on the quality of life(QOL)of stroke patients with hemiplegia.Methods Eighty-two stroke patients were randomly divided into two groups:a rehabilitation group(R group)and a control group.All patients were given routine inter- nal medicine treatment,but STR was also administered to the R group.The QOL of all of the patients was assessed with the brief scale of quality of life(QOL-BREF)at the beginning,and at the end of the Ist month,3rd month and 6th month after stroke.Results There were two deaths in the control group,but no deaths in the R group.At ever- y stage,the R group returned better scores for physiological health,psychological state,social and environment rela- tionships,the subjective QOL and health items,and in comprehensive self-evaluation.QOL scores,except for social relationships,were consistently,significantly higher in the R group.The R group's QOL scores improved obviously in the first 3 months after stroke,and then more slowly in the next 3 months.Conclusions STR markedly improved the QOL of stroke patients.Their QOL scores improved obviously soon after stroke,but slowly later on.

Objective To observe the effects of standardized three stage rehabilitation treatment on the neu- rological deficit scores (NDS) and ADL performance of ischemic stroke patients.Methods A total of 164 ischemic stroke patients were recruited and randomly divided into a rehabilitation group and a control group.The neurological function and ADL performance of the patients were assessed by using NDS and Modified Barthcl Index (MBI) at the admission,at the end of 1st,3rd and 6th months post stroke.Results No significant differences were found be- tween the rehabilitative and the control groups with regard to NDS and MBI at admission.The NDS demonstrated a decreasing tendency,while the MBI score an increasing tendency in both groups.In the control group,significant difference of NDS was found between admission and the end of 1st month as well as between the end of the 1 st and the 3rd months.In rehabilitation group,significant difference was revealed between all the time points with regard to NDS and MBI scores.At the end of the 1st,3rd and 6th months,the MBI scores of the rehabilitation group were signifi- cantly higher than those of the control group,indicating that the ADL performance of those treated with standardized three-stage rehabilitation protocol was improved quicker than those without the protocol.Conclusion Standardized three-stage rehabilitation treatment could improve the neurological function and ADL performance of the ischemic stroke patients.