Objective:To explore the influence of Shenhong Tongluo Granules in the lipid levels,atherosclerosis plaques and apoptosis in the plaques of atherosclerotic apolipoprotein E (ApoE)-knokout mice,and to clarify the mechanism of Shenhong Tongluo Granules in anti-atherosclerosis.Methods:Forty SPF male mice aged six-week old were randomly divided into normal control group,model group,low dose of traditional chinese medicine (TCM) group and high dose of TCM group (n=10)after fed adaptively for 1 week.The mice in normal control group were fed with normal diet continuously, the mice in other three groups were fed with high fat diet to establish atherosclerosis model,and then the mice in low and high doses of TCM groups were respectively given Shenhong Tongluo Granules (5.06 and 10.12 g·kg-1 · d-1 )by gavage for 6 weeks. The levels of serum total cholesterol (TC),triglycerides (TG),low density lipoprotein cholesterol (LDL-C)and high density lipoprotein cholesterol (HDL-C)of the mice in various groups were measured after the eyeball blood was collected.The aortic arch tissue was separated,and the morphotogy and the areas of atherosclerotic plaques were observed and calculated by HE staining;the apoptosis in plaques of the mice was evaluated by TUNEL method, and the apoptosis index was calculated. The expressions of apoptosis-assoicated gene Bcl-2 and Bax protein were measured by immunohistochemical staining.Results:The serum level of TG in low dose of TCM group was lower than that in model group (P <0.05);the serum levels of HDL-C in low and high doses of TCM groups were lower than that in model group (P <0.05 or P <0.01);the serum levels of TG and HDL-C in high dose of TCM group was higher than that in low dose of TCM group (P <0.05).The areas of atherosclerotic plaques of the mice in low and high doses of TCM groups were significantly smaller than that in model group (P <0.01).The apoptosis index of mice in low and high doses of TCM groups were significantly lower than that in model group (P <0.01);the expression levels of Bcl-2 protein in atherosclerosis plaques of the mice in low and high doses of TCM groups were lower than that in model group,while the expression levels of Bax were significantly higher than that in model group (P <0.05 or P <0.01).Conclusion:Shenhong Tongluo Granules could effectively reduce the serum lipid level of ApoE-/-mice,meanwhile it could inhibit apoptosis by regulating the expressions of Bcl-2 and Bax protein,and then inhibit the progression of atherosclerotic plaques.

Objective:To explore the influence of rosuvastatin in the lipid levels, atherosclerosis plaque and apoptosis in the plaque of atherosclerotic apolipoprotein E (ApoE)-knockout mouse models, and to clarify the mechanism of rosuvastatin in inhibiting atheromatous plaque and apoptosis in the plaque.Methods:Thirty healthy six-week old male mice were randomly divided into high fat diet group (n=10),rosuvastatin group (n=10)and general diet control group (n=10).The mice in first two groups were fed with high fat diet,and the mice in general diet control group were fed with general diet;4 weeks later the mice in three groups were respectively given 0.9% NaCl solution,rosuvastatin (10 mg·kg·d-1 )and 0.9% NaCl solution by gavage for 8 weeks.And then ELISA was used to detect the serum lipid levels,the area of atherosclerotic plaque was measured by HE staining, and the apoptosis in plaques was detected by TUNEL method;the expression of apoptosis-assoicated gene Bax protein was measured by immunohistochemical staining.Results:Compared with high fat diet group,the levels of total cholesterol (TC)and low density lipoprotein cholesterol (LDL-C)of the mice in rosuvastatin group were significantly decreased (P<0.05 or P<0.01),and the 1evel of high density lipoprotein cholesterol (HDL-C)was significantly increased (P<0.01).The aortic atherosclerotic plaque of the mice in high fat diet group was massive with a great quantity of foam cells, cholesterol crystal, necrotic cells and inflammatory cells in the plaque;the aortic atherosclerotic plaque of the mice in rosuvastatin group was smaller with less foam cells,necrotic cells and inflammatory cells;the aortic atherosclerotic plaque area of the mice in rosuvastatin group was significantly smaller than that in high fat diet group (P<0.01);the apoptotic index in the aortic atherosclerotic plaque of the mice in rosuvastatin group was significantly lower than that in high fat diet group (P<0.01).Compared with high fat diet group,the expression of Bax protein in rosuvastatin group was significantly decreased.Conclusion:Rosuvastatin may inhibit the progression of atherosclerotic plaque and the apoptosis in plaques through mitochondrial pathway.

OBJECTIVETo detect potential mutation in a Chinese family affected with succinic semialdehyde dehydrogenase deficiency.

METHODSGenomic DNA was extracted from the peripheral blood samples of the proband, her family members and 100 healthy controls. All exons and flanking intronic regions of the ALDH5A1 gene were amplified by PCR and subjected to direct sequencing.

RESULTSThe proband was found to have compound heterozygous mutations of the ALDH5A1 gene, namely c.398_399delAA (p.N134X) and c.638G>T (p.R213L), for which her parents were both heterozygous carriers. The same mutations were not found among the 100 healthy controls.

CONCLUSIONThe novel mutations of the ALDH5A1 gene probably underlie the pathogenesis of the disease in the infant, which also enriched the mutation spectrum of the ALDH5A1 gene.

Amino Acid Metabolism, Inborn Errors ; ethnology ; genetics ; Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; DNA Mutational Analysis ; methods ; Developmental Disabilities ; ethnology ; genetics ; Exons ; genetics ; Family Health ; Female ; Heterozygote ; Humans ; Infant ; Introns ; genetics ; Male ; Mutation ; Sequence Homology, Amino Acid ; Succinate-Semialdehyde Dehydrogenase ; deficiency ; genetics

In recent years, immune checkpoint inhibitors (ICIs) have been widely used in malignant solid tumors with remarkable efficacy. However, in colorectal cancer (CRC), ICIs have shown significant therapeutic effects only in patients with highly microsatellite unstable/mismatch repair-deficient metastatic CRC and these patients are only a minority of all CRC patients. In contrast, the majority of patients, those with microsatellite stable (MSS)/mismatch repair-complete (pMMR)-type metastatic CRC, could hardly benefit from ICI monotherapies, and immune combination therapies have become the key to solveing this clinical challenge. This article introduces the common patterns and possible mechanisms of immune-combination therapies for MSS/pMMR-type CRC, the exploration and progress made in the application of immune-combination therapies, as well as the possible predictive markers of efficacy of immune therapies. The prospects and directions of ICIs in the treatment of MSS/pMMR-type CRC are also discussed.

In recent years, immune checkpoint inhibitors (ICIs) have been widely used in malignant solid tumors with remarkable efficacy. However, in colorectal cancer (CRC), ICIs have shown significant therapeutic effects only in patients with highly microsatellite unstable/mismatch repair-deficient metastatic CRC and these patients are only a minority of all CRC patients. In contrast, the majority of patients, those with microsatellite stable (MSS)/mismatch repair-complete (pMMR)-type metastatic CRC, could hardly benefit from ICI monotherapies, and immune combination therapies have become the key to solveing this clinical challenge. This article introduces the common patterns and possible mechanisms of immune-combination therapies for MSS/pMMR-type CRC, the exploration and progress made in the application of immune-combination therapies, as well as the possible predictive markers of efficacy of immune therapies. The prospects and directions of ICIs in the treatment of MSS/pMMR-type CRC are also discussed.

Objective This study aimed to investigate the levels of non-enzymatic antioxidants among patients with depression at different age stages.Methods One hundred thirty five patients with depression(including 63 elderly patients aged 60 years and older,and 72 young and middle-aged patients under 60 years old)and 98 healthy controls(including 46 elderly controls aged 60 years and older,and 52 young and middle-aged controls aged under 60 years old)were enrolled.Serum levels of non-enzymatic antioxidants(uric acid,total bilirubin,albumin)were assessed.Results Multiple analysis of variance showed the main effects of depression factors on uric acid and total bilirubin were significant(P<0.05).Uric acid[(314.30±85.18)μmol/L vs.(339.68±85.27)μmol/L],total bilirubin[(12.81±6.16)μmol/L vs.(15.09±5.97)μmol/L]levels were lower in patients with depression than in controls(P<0.05).There was an interactive effect between age and depression factors on the levels of albumin(P<0.001),and the levels of albumin[(41.05±3.97)g/L vs.(46.01±4.49)g/L]were lower in group of the elderly patients with depression than those in group of the young and middle-aged patients with depression(P<0.01).Conclusion Patients with depression have abnormalities in levels of non-enzymatic antioxidants which are more severe in elderly patients.

Objective: To study the clinical and laboratory diagnosis and follow-up of 4-hydroxy butyrate aciduria in children. Methods: From June 2012 to July 2017, 9 cases in Tianjin Children′s Hospital were analyzed.According to their clinical features, multidimensional analysis was performed by using head magnetic resonance imaging (MRI), urine gas chromatography-mass spectrometry (GC/MS) semi-quantitative testing and gene mutation analysis of ALDH5A1. Results: The onset age of the 9 cases was less than 1 year old, and all had psychomotor retardation, in which 4 cases with epileptic seizures, 1 case with consciousness disturbance and 1 case with involuntary movement.All the cases underwent head MRI and 4 cases showed bilateral symmetry pallidal lesions, including 1 case with symmetry abnormality of the midbrain cerebral peduncle, 1 case with encephalomalacia in left temporal cortex and 4 cases with widening of the ventricle and extracerebral space.By the urine GC/MS semi-quantitative testing, all 9 the cases showed increasing 4-hydroxy butyric acid and by the ALDH5A1 gene mutation analysis, all 9 the cases were detected with gene mutation (3 cases belonging to c. 1568C>T homozygous mutation, 1 case belonging to c. 839T>G homozygous mutation and the other 5 cases belonging to compound heterozygous mutation, which included c. 691G>A, c.1568C>T; c.1383_2delA, c.1568C>T; c.527G>A, c.691G>A; c.904G>A, c.1022C>A; c.398_399delA, c.638G>T). Nine cases were given symptomatic treatment, and 4 cases with epileptic seizures were given antiepileptic drugs.During the follow-up of the above 9 cases, 1 case died of status epilepticus, 1 case had been under control for 5 years, and 2 cases were effectively treated.Psychomotor retardation was improved in varying degrees in 8 cases.Involuntary movement disappeared in 1 case while 2 cases still showed increasing 4-hydroxy butyric acid by means of urine GC/MS semi-quantitative testing. Conclusions Most of 4-hydroxy butyrate aciduria occurs within 1 year old, with psychomotor development as the first manifestation, which can be associated with epilepsy.The head MRI is characte-rized by a symmetrical Globus pallid abnormal signal.Urine GC/MS shows an increase in 4-hydroxy butyrate, which is the basis for biochemical diagnosis of the disease.Its accumulation in the body mainly damages the central nervous system.ALDH5A1 is a disease-causing gene, in which c. 1568C>T site has a high mutation frequency, and it is speculated that this site may be a hot spot mutation in Chinese children.Patients with epilepsy may die from status epilepticus and may be used as a clinical indicator to judge the severity of the disease.There is no specific treatment, and the patients combined with epilepsy can be treated with anti-epileptic drugs.Valproic acid should be avoided as it can aggravate the condition.

Objective To investigate the effects of Carthamus tinctorius L.extract(CTLE)on the levels of oxidative stress and inflammation in mice with ethanol-induced alcoholic liver disease and its mechanism of action.Methods SPF-grade C57BL/6 male mice were randomly divided into four groups:control group,model group,low-CTLE group(50 mg·kg-1),and high-CTLE group(100 mg·kg-1).The control group was given Lieber-Decarli liquid diet,and the other groups were given Lieber-Decarli alcohol diet to construct a chronic alcoholic liver injury model in mice.Serum and liver tissues of mice were collected and serum biochemical indexes of mice were detected.HE and oil red O staining were applied to observe pathological changes in mouse liver tissues.Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression levels of Keap1/Nrf2 and STAT3/NF-κB pathway-related factors.Results Compared with the model group,the ALT,AST,LDL-C,and MDA levels were significantly reduced(P＜0.05,P＜0.01),while the levels of HDL-C,SOD,and GSH were increased dramatically in the administered group(P＜0.05,P＜0.01),which indicated that CTLE has specific protective and antioxidant effects on alcoholic liver injury in mice.HE staining and oil red O staining showed that the hepatic lesions and lipid deposition of mice were ameliorated.It enhances the antioxidant and anti-inflammatory effects of the body by activating the mRNA and protein expression levels of antioxidant factors related to the Keap1/Nrf2 pathway and inhibiting the mRNA and protein expression levels of inflammatory factors related to STAT3/NF-κB pathway(P＜0.05,P＜0.01).Conclusion It was shown that CTLE could exert anti-oxidative stress and anti-inflammatory effects through regulating Keap1/Nrf2 and STAT3/NF-κB signaling pathways to attenuate alcoholic liver injury in mice.This study may provide a new idea for the treatment of alcoholic liver disease and the subsequent study of molecular mechanisms.