Inhibition of glutaminolysis alleviates myocardial fibrosis induced by angiotensin II / 生理学报

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.

Ketogenic diet improves low temperature tolerance in mice by up-regulating PPARα in the liver and brown adipose tissue / 生理学报

The aim of the present study was to investigate the effects of short-term ketogenic diet on the low temperature tolerance of mice and the involvement of peroxisome proliferator-activated receptor α (PPARα). C57BL/6J mice were divided into two groups: normal diet (WT+ND) group and ketogenic diet (WT+KD) group. After being fed with normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The changes in core temperature, blood glucose, blood pressure of mice under low temperature condition were detected, and the protein expression levels of PPARα and mitochondrial uncoupling protein 1 (UCP1) were detected by Western blot. PPARα knockout mice were divided into normal diet (PPARα-/-+ND) group and ketogenic diet (PPARα-/-+KD) group. After being fed with the normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The above indicators were also detected. The results showed that, at room temperature, the protein expression levels of PPARα and UCP1 in liver and brown adipose tissue of WT+KD group were significantly up-regulated, compared with those of WT+ND group. Under low temperature condition, compared with WT+ND, the core temperature and blood glucose of WT+KD group were increased, while mean arterial pressure was decreased; The ketogenic diet up-regulated PPARα protein expression in brown adipose tissue, as well as UCP1 protein expression in liver and brown adipose tissue of WT+KD group. Under low temperature condition, compared to WT+ND group, PPARα-/-+ND group exhibited decreased core temperature and down-regulated PPARα and UCP1 protein expression levels in liver, skeletal muscle, white and brown adipose tissue. Compared to the PPARα-/-+ND group, the PPARα-/-+KD group exhibited decreased core temperature and did not show any difference in the protein expression of UCP1 in liver, skeletal muscle, white and brown adipose tissue. These results suggest that the ketogenic diet promotes UCP1 expression by up-regulating PPARα, thus improving low temperature tolerance of mice. Therefore, short-term ketogenic diet can be used as a potential intervention to improve the low temperature tolerance.

Evaluation of the safety and efficacy of transcatheter aortic valve replacement with domestic prostheses for patients with severely stenotic bicuspid aortic valve / 中华心血管病杂志

Objective: To evaluate the safety and efficacy of transcatheter aortic valve replacement (TAVR) with domestic prostheses in patients with severely stenotic bicuspid aortic valve (BAV). Methods: This study was a prospective single-center non-randomized controlled study. Patients with symptomatic severe aortic stenosis (AS), who underwent TAVR with domestic prostheses at the First Affiliated Hospital of Air Force Medical University from January 2016 to April 2020 were consecutively included in our study. Patients were divided into BAV group and tricuspid aortic valve (TAV) group according to the aortic valve morphology. Baseline characteristics, procedural outcomes were compared between the two groups, and the primary endpoint was one-month all-cause mortality. Results: A total of 100 patients aged (69.8±8.9) years were enrolled, including 71 (71%) males. There were 51 cases in BAV group and 49 cases in TAV group. Compared with TAV group, patient in the BAV group was younger ((67.1±8.6) years vs. (72.7±8.4) years, P=0.002) and had larger ascending aortic diameter at proximal part ((39.7±5.7) mm vs. (36.0±4.2) mm, P<0.001), lower Society of Thoracic Surgeons-Predicted Risk of Mortality (STS-PROM) score (3.1 (1.9, 5.4) % vs. 5.9 (2.6, 12.3) %, P=0.002). In BAV group and TAV group, the incidence of 2nd prosthesis implantation was 15.7% (8/51) and 18.4% (9/49) (P=0.721), the incidence of moderate or severe paravalvular regurgitation was 2.0% (1/51) and 0 (P=1.000), the rate of device success was 82.4% (42/51) and 81.6% (40/49) (P=0.925), respectively. One-month all-cause mortality was 2.0% (1/51) and 10.2% (5/49) (P=0.108), respectively. Echocardiography showed that postprocedural mean pressure gradient (PGmean) was higher in the BAV group (13.0 (10.0, 16.0) mmHg vs. 9.0 (7.0, 14.0) mmHg, P=0.003) (1 mmHg=0.133 kPa), but the PGmean decrease post procedure as compared with that before TAVR was similar between the two groups ((36.7±16.6) mmHg vs. (36.2±17.5) mmHg, P=0.893). Conclusion: Favorable safety and efficacy are evidenced in patients with severely stenotic BAV undergoing TAVR with domestic prostheses.

Distribution and Drug Sensitivity of Pathogens Causing Nosocomial Infection in Patients with Hematological Granulocytosis / 中国实验血液学杂志

OBJECTIVE@#To investigate the distribution and drug resistance of nosocomial infection pathogens in AL patients with hematological agranulocytosis, so as to provide evidence for the clinical rational use of antibiotics.@*METHODS@#Pathogenic data of 504 hospitalized patients with agranulocytosis caused by nosocomial infection in the Department of Hematology, the First Hospital of Lanzhou University from May 2015 to May 2018 were collected and retrospectively analyzed for the distribution of pathogenic bacteria and the results of drug susceptibility.@*RESULTS@#The isolated pathogenic bacteria strains amounted to 184, out of which, 168 strains (91.3%) orginated from the patients with acute leukemia, while 16 strains (8.7%) originated from the patients with non-acute leukemia. The positive samples mainly originated from blood stream, the isolated bacteria from which were 81 straims (44%); then originated from sputam and pharynx swabs, from which isolated bacteria amounted to 54 strains (29.3%) and 35 strains (19%) respectively. In the pathogenic bacteria, the Gram-negative bacteria amounted to 126 strains accounting for 68.46%, out of which the most commond bacteria strains were Klebseilla pneumoniae, cscherichia coli and Pseudomonas aeruginosa; the Gram positive bocteria amounted to 23 strains accounting for 12.5%, mainly staphy lococeus anreus, and Staphylococcus epitermidis; the fungi amounted to 35 strains accounting for 19.02%, mainly Candida albicans. The detection rates of Escherichia coli and Klebsiella pneumoniae producing extended-spectrum β-lactamases (ESBLs) were 40.0% and 22.2%, respectively. They were 100% sensitive to amikacin and 27.8% resistant to carbapenems. Klebsiella pneumoniae had the highest sensitivity to amikacin, 94.44% to ampicillin, 97.22% to carbapenems and 100% sensitive to ammonia. Their penicillin-resistance rate was the highest, up to 80%; Pseudomonas aeruginosa was sensitive to the antibiotics (＞80%）. Methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococcus were detected in Gram-positive bacteria. The susceptibility rate of main Gram-positive bacteria to vancomycin and linezolid was 100%, and they were 100% resistant to penicillin.@*CONCLUSION@#Gram-negative bacteria are the main pathogens of nosocomial infection in patients with hematological agranulocytosis. Pathogens have different resistance to antimicrobial agents. It is important to know the distribution and susceptibility of common pathogens for rational selection of antimicrobial agents and control of nosocomial infection.

Values of Different Prognostical Score Systems in Evaluation of Clinical Efficacy for Patients with Newly Diagnosed Chronic Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the values of 4 prognostic score systems in evaluation of clinical effecacy for patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatnib mesylate (IM) and the relationship between 4 prognostic score systems and deep molecular response (MR4.5).@*METHODS@#The clinical data of 240 CML-CP patients treated with imatinib mesylate in our hospital between Janunay 2008 and December 2017 were analyzed retrospecively. The risk was stratified according to 4 prognostic score systems, the relationship between the 4 prognostic score systems and 3-month early molecular response (3M-EMR), 6 month complete cytogenetic response (6M-CCyR), 12-month major molecular response (12M-MMR) as well as the correlation of the 4 prognostic score systems with deep molecalar response were analyzed.@*RESULTS@#At the end of treatment for 3 months, the EMR was evaluated for 219 patients, among them 164 (74.9%) patients achieved 3M-EMR; at the end of treatment for 6 months, CCyR was evaluated for 180 pathsents, among them 130 (72.2%) patients achicved 6M-CCyR; at the end of treatment for 12 months, the MMR was evaluated for 111 patients, among them 60 (54.1%) patients achieved 12M-MMR. Compared with the high-risk group, the treatment response to IM in the low-risk group (including the low-risk group and the intermediate-risk group) was better. There was significant difference in 3M-EMR according to Sokal score and ELTS score (P＜0.05), and there was significant difference in 12M-MMR according to EUTOS score and ELTS score (P＜0.05). Logistic regression analysis revealed Sokal score (HR=0.69, 95%CI：0.22-1.37, P＜0.05) and 3M-EMR (HR=0.47, 95%CI：0.28-0.84, P＜0.01) independently related with MR4.5, The combination of Sokal score, especially the low risk with 3M-EMR much more can predict MR4.5 (HR=0.42, 95%CI=0.21-0.82, P＜0.01).@*CONCLUSION@#There is a remarkable clinical efficacy of imatinib mesylate on CML-CP patients, moreover, low risk group has a better therapeutic response. Both Sokal score and ELTS score evaluate 3M-EMR better, both EUTOS score and ELTS score evaluate 12M-MMR better. The combination of low risk in Sokal score with 3M-EMR much more can predict MR4.5. The results of this study provide the reference basis for evaluating the clinical therapentic efficacy and timely modifying the therapeutic regimens for CML patients, also possess the reference value for predicting the MR4.5.

Clinical Analysis of Serum Calcium Level in 86 Cases of Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the serum calcium level in 86 patients with newly diagnosed multiple myeloma (MM) and its correlation with clinical features.@*METHODS@#The clinical data of 86 patients with newly diagnosed multiple myeloma in our hospital from 2009 to 2016 were retrospectively analyed. Clinical data of sex, age, hemoglobin, albumin, globulin, creatinine, uric acid, serum phosphorus, β2-microglobulin, immunophenotyping and disease staging were collected. After the serum calcium level was corrected, the patients were grouped into low serum calcium (2.60 mmol/L). The correlation between the clinical characteristics and the serum calcium level was analysed, the clinical characteristics between the low and non-low calcium group were compared.@*RESULTS@#The number of cases in low, normal and high serum cnlcium groups before correction was 58 (67.4%), 18 (20.9%) and 10 (11.6%) respactively, while the number of cases in 3 group after correction was 34 (39.5%), 36 (41.9%) and 16 (18.6%) respectively. The age, globulin, creatinine, uric acid and serum phosphorus levels were positively correlated with serum calcium level in patients with multiple myeloma, while the sex, hemoglobin,albumin and β2-microglobulin levels did not correlated with serum calcium level. There was significant difference in the age, globulin, creatinine and serum phosphorus between low calcium and non-low calcium group (P0.05).@*CONCLUSION@#Multiple myeloma patients suffered from both hypercalcemia and hypocalcemia, and the incidence of hypocalcemia is not low. The levels of serum calcium in patients with multiple myeloma correlate with age, globulin, creatinine, uric acid, serum phosphorus level and other factors, thus it is necessary to correct the level of ionized calcium with physiological activity.

Identification and antimicrobial resistance of Escherichia coli isolates from chicken in different provinces / 中国人兽共患病学报

The aim of this study was to determine the prevalence and antibiotic susceptibility of Escherichia coli from retail raw chickens in different provinces of China.A total of 1 152 whole chicken samples were collected and screened for the prevalence of E.coli,and then the E.coli isolates were further tested for the antimicrobial susceptibility using agar dilution method.Results showed that the overall positive rate for E.coli in retail chickens was 65.97％ (760/1 152);resistance was most common to nalidixic acid (66.84％),followed by amoxicillin-clavulanic acid (66.05％),tetracycline (65.00％),trimethoprim-sulfamethoxazole (63.16 ％),ampicillin (60.66 ％),amoxicillin (51.32 ％),streptomycin (50.39 ％),chloramphenicol (48.32 ％),kanamycin (38.29 ％),gentamicin (26.31％),ciprofloxacin (25.79 ％) and cefoxitin (21.05 ％).The last were gatifloxacin,cefoperazone and amikacin (each ＜20％).Overall,70.53％ of the isolates were resistant to at least three antimicrobials.A large proportion of multidrug resistant isolates were resistant to 8 kinds of antimicrobials (10.26 ％).No strain was resistant to 15 kinds of antimicrobials.Furthermore,isolates recovered from different regions exhibited different resistance levels to most antimicrobials.Our findings indicate that retail chicken in China was commonly contaminated with E.coli,and many E.coli strains exhibited multiple drug resistance.Presence of multiple drug E.coli in raw chickens may pose a potential threat to human health.

Association of Insulin Resistance and β Cell Function with Lipid Metabolism in Middle-aged and Elderly Hui and Han Populations / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the association of insulin resistance and β cell function with lipid metabolism in middle-aged and elderly Hui and Han populations.</p><p><b>METHODS</b>A total of 1000 subjects age over 40 years were recruited from five urban communities in Yinchuan and Wuzhong cities of Ningxia. The composition ratio between Hui and Han nationality was 1:2. A questionnaire-based survey was performed. Physical examinations were carried out to measure the height, body mass, waistline, and hipline. The levels of triglyceride (TG), total cholesterol (TC), blood uric acid (BUA), fasting blood glucose and insulin were measured. The boby mass index (BMI), waist-hip ratio (WHR), and secretion related index including insulin resistance index (IR), insulin sensitivity index (IAI), and beta cell function index (HBCI) were calculated.</p><p><b>RESULTS</b>The BMI, WHR, IAI, HBCI, and the prevalence rate of diabetes in Hui nationality were significantly higher than those in Han nationality (P<0.01). The levels of BUA, fasting blood glucose, TC, and IR in Han nationality were significantly lower than those in Hui nationality (P<0.01). In Hui populations, TG, BMI, WHR, and BUA were positively correlated with IR (r=0.234, r=0.193, r=0.143, and r=0.129, respectively; P<0.01) and were negatively correlated with IAI (r=-0.234, r=-0.193, r=-0.143, r=-0.129, respectively; P<0.01), whereas TC was negatively correlated with HBCI (r=-0.169, P<0.01). In Han populations, TC, TG, BMI, WHR, and BUA were positively correlated with IR (r=0.140, r=0.257, r=0.288, r=0.163, r=0.104, P<0.01) and negatively correlated with IAI (r=-0.140, r=-0.257, r=-0.288, r=-0.163, and r=-0.104, P<0.01), whereas BMI was negatively correlated with HBCI (r=-0.111, P<0.01). After the influential factors such as gender, nationality, and age were adjusted, the TC, TG, BMI, WHR, BUA levels were positively correlated with IR (r=0.109, r=0.256, r=0.253, r=0.139, and r=0.142, P<0.01) and negatively correlated with IAI (r=-0.109, r=-0.256, r=-0.253, r=-0.139, and r=-0.142, P<0.01). TC and BMI were negatively correlated with HBCI (r=-0.113, r=-0.086, P<0.01). TG and BMI were independently associated with IR and IAI (r=0.218, r=0.182, r=-0.218, r=-0.182), while TC and BMI were independently associated with HBCI (r=-0.113, r=-0.086).</p><p><b>CONCLUSIONS</b>The distributions of TC, TG, BMI, WHR, BUA, IR, IAI, and HBCI differ between Han and Hui populations. The development of insulin resistance is closely related with the increased levels of TC, TG, BMI, WHR, and BUA. However, the HBCI increases with the increased level of TC and BMI. TG and BMI may be related with insulin resistance. Also, TC and BMI may affect the secretion function of β cells.</p>

Intervention of berberine on lipid deposition in liver cells of non-alcoholic fatty liver disease rats induced by high fat diet / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of berberine on lipid metabolism disorder and lipid deposition in liver cells of non-alcoholic fatty liver disease (NAFLD) rats induced by high fat diet.</p><p><b>METHODS</b>After one week adaptable feeding, 45 SPF level male SD rats were randomly divided into 3 groups, the normal control group, the model group, and the berberine group, 15 in each group. Except those in the normal control group, all rats were fed with high fat diet to prepare NAFLD model. As for rats in the berberine group, Berberine Hydrochloride was administered by gastrogavage. HE staining and oil red O staining were performed to identify the model after 8 weeks. Hepatocytes were isolated, and their activities and purities were tested by Typan blue staining and flow cytometry (FCM). Serum levels of TC, TG, HDL-C, and LDL-C were detected using automatic biochemical analyzer. mRNA expression levels of LXRα and FAS in liver cells were analyzed by Real-time quantitative polymerase chain reaction (PCR). Protein levels of LXRα and FAS in liver cells were examined by Western blot.</p><p><b>RESULTS</b>The NAFLD rat model was successfully established by high fat diet. The yields of purified liver cells in each rat were (6.0-7.5) x 10(8). The viability of isolated liver cells with purity over 90% (tested by FCM analysis) was higher than 95%. Compared with the normal control group,the expression of LXRα and FAS at mRNA and protein levels was higher in the model group (P < 0.01). Compared with the model group, the expression of LXRα and FAS at mRNA and protein levels was obviously down-regulated in the berberine group (P < 0.01).</p><p><b>CONCLUSIONS</b>LXRα/FAS signaling pathway was one of important signaling pathways of NAFLD lipid metabolism disorders. Berberine could recover hepatocyte fatty deposits in NAFLD rats by adjusting the LXR/FAS signaling pathway of hepatocytes, which might be one of important mechanisms for fighting against NAFLD.</p>