The afsRS(cla) global regulatory genes from Streptomyces clavuligerus activate the production of two antibiotics in Streptomyces lividans. In this study, we gained an increase of 38% in the production of natamycin (3.56 g/L) in an industrial strain Streptomyces gilvosporeus TZ1401 through the integration of pHL851 that bears the afsRS(cla) global regulatory genes into its genome. We discovered by quantitive real-time reverse transcription PCR (qRT-PCR) that the expression of 6 genes of the natamycin biosynthetic gene cluster were improved from 1.9 to 2.7 times. This suggests that afsRS(cla) improve the production of natamycin through increased transcription. This study provides a good example for applying afsRS(cla) in high yield breeding of industrial antibiotic producers.
Anti-Bacterial Agents ; biosynthesis ; Genes, Regulator ; Industrial Microbiology ; Multigene Family ; Natamycin ; biosynthesis ; Streptomyces ; genetics

Background:Gastroesophageal reflux disease(GERD)is a common disease,its incidence is related to geographic environment and race. Studies reported on epidemiology of GERD in minority groups are rare. Aims:To investigate the prevalence and related risk factors of GERD in She population in Ningde. Methods:Three natural villages of She population in Ningde were selected for undergoing the cluster random sampling method. GERD was diagnosed by gastroesophageal reflux disease questionnaire(GerdQ)with score ≥8,and questionnaire was used to detect the prevalence and risk factors of GERD. Results:A total of 936 residents completed the questionnaire,and 89 were diagnosed as GERD, the prevalence was 9. 50% . Univariate analysis showed that the risk of GERD was significantly increased in She population with body mass index(BMI)≥24 kg/ m2 ,intake of strong tea or oily diet(P all < 0. 01). Multivariate analysis showed that BMI ≥24 kg/ m2(OR = 3. 022,95% CI:1. 917-4. 765),intake of strong tea(OR = 2. 145,95% CI:1. 338-3. 438) and oily diet(OR = 2. 016,95% CI:1. 208-3. 318)were the risk factors of GERD. Conclusions:The prevalence of GERD is high in She population in Fujian Province,and the etiology may be related to overweight and diet habit.

Objective To investigate the activation, distribution, origin, and expression of hepatic stem cells(HSC)in different histological types of primary liver carcinomas. Methods The histological and immunohistochemical features of 94 cases of hepatocellular carcinoma (HCC), 12 cases of intrahepatic cholangiocarcinoma (ICC) and 10 cases of mixed hepatocarcinoma were examined by HE staining and immunohistochemistry SP method, with 5 cases of sclerotic liver and 4 cases of normal liver tissues as control. Results HSC expression was observed and the transfor mation from HSC to carcinoma cell was also noted in the liver. CK7, CK19, c-kit, Thy-1, and AFP were found expressed in different types of hepatic carcinomas and the greatest intensive expression was found in the mixed hepatocarcinoma (P

OBJECTIVETo investigate the correlation of neurochemical metabolism in hippocampus with memory function in young adult patients with first-episode depression.

METHODSTwenty patients with first-episode depression (patient group) and fifteen health subjects (control group) were enrolled in the study. The neurochemical metabolism, including the levels of N-acetylaspartate (NAA), Choline (Cho), Creatine (Cr), Myoinositol (mI) were measured by proton magnetic resonance spectroscope (1H-MRS) in bilateral hippocampus. Wechsler Memory Scale (WMS) were used to examine the memory function in both groups.

RESULTSThe memory quotient (89.15 ±6.62) of patient group was significantly lower than that of controls (P <0.01),the scores of long-term memory,short-term memory and immediate memory in patients were also lower than those of controls (P<0.05 or 0.01). In patient group, the ratio of NAA/Cr (1.34 ±0.08) in the left hippocampus was significantly lower than that of control group (P<0.01); and the ratio of mI/Cr in the bilateral hippocampus [(0.63 ±0.13) in left and (0.6 ±0.1) in right] was significantly higher than those in control group (P<0.05). In patient group,the ratio of NAA/Cr in the left hippocampus was positively correlated with WMS scores (P<0.01), and the ratio of mI/Cr in the left hippocampus was negatively correlated with WMS scores (P<0.05).

CONCLUSIONThe memory deficit and abnormal metabolism function of neuron cell in hippocampus coexist in young adult patients with first-episode depression, and the lower NAA/Cr and higher mI/Cr ratio in the left hippocampus may result in the memory deficit.

Adolescent ; Adult ; Aspartic Acid ; analogs & derivatives ; metabolism ; Case-Control Studies ; Creatine ; metabolism ; Depressive Disorder ; metabolism ; physiopathology ; Female ; Hippocampus ; metabolism ; Humans ; Inositol ; metabolism ; Magnetic Resonance Spectroscopy ; Male ; Memory ; Neuropsychological Tests ; Young Adult

A total of 280 patients with varicose veins of lower extremities who were prescribed stretch socks as pressure therapy in the outpatient clinic of Beijing Chaoyang Hospital from September 2019 to November 2019 were included in the study. Among 280 patients 208 were followed up for one year(74.3%), 139 cases (66.8%) gave up wearing stretch socks and 69 cases (33.2%) insisted to wear. The main reasons for giving up wearing were feeling too tight (23.1%), too much troubles (17.7%), symptom improvement (15.1%), poor effect (10.8%) and so on. The compliance of wearing stretch socks as pressure therapy in outpatients with varicose veins of lower extremities is poor with a variety of reasons, the data may provide a reference for improving clinical compliance in the future.

Objective To investigated the changes of angiopoietin-like protein 2(Angptl2) in patients with arteriosclerotic occlusion (ASO). Methods A total of 140 subjects including 75 ASO patients (ASO group) and 65 healthy subjects (control group) were enrolled in this study. Angptl2 and adiponectin were evaluated by using enzyme-linked immunosorbent assay. Biochemical data and high sensitive C reactive protein were measured and recorded as well. Results Compared to the control group,the ASO group presented with significantly higher level of plasma Angptl2 [(13.55±9.17) μg/L vs. (9.04±4.79) μg/L,P=0.010]. Plasma Angptl2 level of critical limb ischemia subjects was significantly higher than that of intermittent claudication subjects [(17.01±10.20)μg/L vs. (10.53±6.97) μg/L,P=0.003]. The best diagnostic cutoff value of Angptl2 was 13.67 μg/L,with a sensitivity of 60.34% and a specificity of 81.25%. In addition,type 2 diabetes mellitus patients with ASO exhibited significantly higher serum Angptl2 levels [(18.67±9.84)μg/L] than those without ASO [(13.01±3.47) μg/L] (P=0.021). In ASO group,serum Angptl2 levels were negatively correlated with ankle brachial index (r=-0.244,P=0.035). Conclusion The plasma level of Angptl2 increases in ASO patients. Its level is remarkably increased when the disease progressions to critical limb ischemia. Angptl2 can be a potential biological marker of disease progression.

In environmental epidemiological research, extensive non-random environmental exposures and complex confounding biases pose significant challenges when attempting causal inference. In recent years, the introduction of causal inference methods into observational studies has provided a broader range of statistical tools for causal inference research in environmental epidemiology. The instrumental variable (IV) approach, as a causal inference technique for effectively controlling unmeasured confounding factors, has gradually found application in the field of environmental epidemiological research. This article reviewed the basic principles of IV and summarized the current research progress and limitations of applying IV for causal inference in environmental epidemiology. IV application in the field of environmental epidemiology is still in the initial stage. Rational use of IV and effective integration with other causal inference methods will become the focus of the development of causal inference in environmental epidemiology. The aim of this paper is to provide a methodological reference and basis for future studies involving causal inference to target population health effects of environmental exposures in China.

Objective: To examine the association between long-term exposure to ambient PM_2.5 combined with indoor air pollution and handgrip strength among people aged 50 and over. Methods: Data were from the first wave of World Health Organization Study on global AGEing and adult health in China. Ambient annual concentration of PM_2.5 was estimated by using the satellite data we also investigated the use of fuels and chimneys as indoor air pollution. A two-level (individual level and community level) linear model was applied to examine the association between long-term exposure to ambient PM_2.5 combined with indoor air pollution and the handgrip strength. Results: A total of 13 175 individuals aged 50 years and over were included for analysis. The handgrip strength was (26.67±0.54) kg. Ambient PM_2.5 was found to be significantly associated with the risk of decreased handgrip strength. Outdoor PM_2.5 concentration was negatively correlated with handgrip strength (β=-0.23, 95%CI: -0.31 - -0.14) decrease in handgrip strength after adjusting for gender, age, residence, education, household assets, intake of vegetables and fruits, smoking and drinking, physical activity. In rural area, compared to those who used solid fuel, use of clean fuel increased (β=1.41, 95%CI: 0.36-2.46) handgrip strength. But in urban area, we did not find any statistically significant association between the use of clean fuel and handgrip strength (β=0.19, 95%CI: -0.95-1.32). Conclusion This study found that long-term exposure to ambient PM_2.5 combined with indoor air pollution was significantly associated with low handgrip strength among people aged 50 years and over, this suggested that ambient PM_2.5 might serve as one of the risk factors for low physical function seen in the people aged 50 years and over.

Ulcerative colitis （UC） is a commonly seen digestive system disease with unclear pathogenesis. The condition is complex and variable， often chronic， and has a long treatment period with no specific cure. Currently， the treatment of UC often involves the use of corticosteroids， aminosalicylates， and biologics in western medicine， which provide fast-acting and definite efficacy in the short term. However， with prolonged medication， some patients may develop drug resistance and worsening of the disease， leading to the occurrence of colon cancer. Research has found that oxidative stress is one of the important pathogenic factors in UC and influences its onset and development. Oxidative stress is a state of imbalance between oxidative products and the antioxidant system in the body， characterized by overexpression of oxidative products such as malondialdehyde （MDA）， reactive oxygen species （ROS）， nitric oxide （NO）， or deficiency of antioxidant enzymes such as superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH）. It is worth noting that traditional Chinese medicine （TCM）， as a unique characteristic medicine of China， has achieved significant efficacy in the treatment of UC. Studies have shown that TCM effectively inhibits the occurrence of UC by suppressing the accumulation of metabolites and antagonizes the development of UC by enhancing the antioxidant system. Therefore， using TCM to regulate the oxidative balance as a diagnostic and therapeutic approach may be a new method and direction for the treatment of UC in the future. Based on the above research， this article summarized the mechanisms of key pathogenic proteins in oxidative stress and the occurrence and development of UC， and compiled the effective ingredients of Chinese medicine， single drugs， prescriptions， and acupuncture and moxibustion in regulating upstream and downstream target proteins of oxidative stress. These interventions can reduce pathological damage to the intestinal mucosa， lower the colon injury index， enrich the intestinal microbiota， increase colon length， and improve clinical symptoms of UC. The article is expected to expand the application of TCM in the treatment of UC and provide a reliable scientific theoretical basis.

Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 µmol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders.