Promoting reverse cholesterol transport contributes to the amelioration of atherosclerosis by paeoniflorin.

Reverse cholesterol transport (RCT) offers a practical approach to mitigating atherosclerosis. Paeoniflorin, a monoterpenoid glycoside found in plants of the Paeoniaceae family, has shown various effects on cardiovascular and liver diseases. Nevertheless, its impact on atherosclerosis in vivo remains poorly understood. The objective of this study is to examine the effect of paeoniflorin on atherosclerosis using apolipoprotein E-deficient (ApoE-/-) mice and explore the underlying mechanisms, with a specific focus on its modulation of RCT. ApoE-/- mice were continuously administered paeoniflorin by gavage for three months. We assessed lipid parameters in serum and examined pathological changes and gene expressions related to RCT pathways in the aorta, liver, and intestine. In an in vitro study, we utilized RAW264.7 macrophages to investigate the inhibitory effect of paeoniflorin on foam cell formation and its potential to promote RCT. The results revealed that paeoniflorin reduced atherosclerosis, alleviated hyperlipidemia, and mitigated hepatic steatosis. Paeoniflorin may promote RCT by stimulating cholesterol efflux from macrophages via the liver X receptor alpha pathway, enhancing serum high-density lipoprotein cholesterol and apolipoprotein A-I levels, and regulating key genes in hepatic and intestinal RCT. Additionally, treatment ApoE-/- mice with paeoniflorin suppressed the expression of inflammation-related genes, including CD68, tumor necrosis factor alpha, and monocyte chemoattractant protein-1, and mitigated oxidative stress in both the aorta and liver. Our results indicated that paeoniflorin has the potential to be a more effective and safer treatment for atherosclerosis, thanks to its promotion of RCT and its anti-inflammatory and anti-oxidative effects.

Mechanism of ophiopogonin D in treatment of pulmonary fibrosis based on network pharmacology and experimental verification / 中国药理学通报

Aim To predict the potential mechanism of ophiopogonin D (OPD) against pulmonary fibrosis by network pharmacology, and further verify it by experiment in vivo. Methods This study found that ophiopogon was the most frequently used drug in the treatment of pulmonary fibrosis with deficiency of Qi and Yin through data mining. In order to explore its material basis, network pharmacology analysis was carried out. A model of pulmonary fibrosis was established by bleomycin, and different concentrations of ophiopogonin D were administered to verify the results of the pharmacological network. Results Firstly, through network pharmacology analysis, it was found that mitophagy might be the potential target for ophiopogon to exert anti-pulmonary fibrosis effect. Meanwhile, network topology analysis showed that OPD had the greatest relationship with mitophagy. Animal experiments showed that OPD could relieve pulmonary fibrosis and reduce collagen deposition in mice. At the same time, the detection of mitophagy related proteins showed that the compound could increase the expression of PINK1 and Parkin proteins, reduce the content of P62 protein in lung tissue, and reduce the intracellular ROS level. Conclusions OPD can improve mitochondrial function and play an anti-pulmonary fibrosis role by promoting PINKl/Parkin dependent mitophagy in lung tissue.

Clinical application and pharmacokinetic study of nanocarriers in drug delivery system / 药学学报

Nanotechnology has shown obvious advantages in the field of medical treatment and diagnosis. Through the encapsulation of nano carriers, drugs not only enhance the therapeutic effect and reduce toxic and side effects, but also become intelligent responsive targeted drug systems through the modification on the surface of nano carriers. However, due to the obstacles in relevant basic research, production conditions, cost, clinical trials, and the lack of pharmacokinetic research on various drug loading systems, few nano systems have been used in therapy. In order to solve the above problems, this paper reviewed and analyzed the research progress of nano carriers in drug delivery, including their auxiliary role and characteristics, types and functions, pharmacokinetics, application prospects and challenges.

Grass Carp Reovirus Nonstructural Proteins Avoid Host Antiviral Immune Response by Targeting the RLR Signaling Pathway.

Grass carp reovirus (GCRV) is a highly virulent RNA virus that mainly infects grass carp and causes hemorrhagic disease. The roles of nonstructural proteins NS38 and NS80 of GCRV-873 in the viral replication cycle and viral inclusion bodies have been established. However, the strategies that NS38 and NS80 used to avoid host antiviral immune response are still unknown. In this study, we report the negative regulations of NS38 and NS80 on the RIG-I-like receptors (RLRs) antiviral signaling pathway and the production of IFNs and IFN-stimulated genes. First, both in the case of overexpression and GCRV infection, NS38 and NS80 inhibited the IFN promoter activation induced by RIG-I, MDA5, MAVS, TBK1, IRF3, and IRF7 and mRNA abundance of key antiviral genes involved in the RLR-mediated signaling. Second, both in the case of overexpression and GCRV infection, NS38 interacted with piscine TBK1 and IRF3, but not with piscine RIG-I, MDA5, MAVS, and TNF receptor-associated factor (TRAF) 3. Whereas NS80 interacted with piscine MAVS, TRAF3, and TBK1, but not with piscine RIG-I, MDA5, and IRF3. Finally, both in the case of overexpression and GCRV infection, NS38 inhibited the formation of the TBK1-IRF3 complex, but NS80 inhibited the formation of the TBK1-TRAF3 complex. Most importantly, NS38 and NS80 could hijack piscine TBK1 and IRF3 into the cytoplasmic viral inclusion bodies and inhibit the translocation of IRF3 into the nucleus. Collectively, all of these data demonstrate that GCRV nonstructural proteins can avoid host antiviral immune response by targeting the RLR signaling pathway, which prevents IFN-stimulated gene production and facilitates GCRV replication.

The correlation of sleep duration and insomnia with low muscle mass, strength and quality in Chinese adults / 中华流行病学杂志

Objective: To explore the relationship of sleep duration and insomnia with muscle mass, strength, and quality in Chinese adults. Methods: Based on the second resurvey of China Kadoorie Biobank (CKB) in 2013-2014, logistic regression models were used to analyze the correlation of sleep duration, insomnia, and its duration with low muscle mass, handgrip strength, and muscle quality. Results: The average sleep duration of the study population was (7.4±1.5) hours. Morbidities of short sleep duration (<6 hours), long sleep duration (≥9 hours), and insomnia were 9.3%,17.4%,and 29.9%,respectively. Compared with those who slept for 7- hours, those who slept for ≥9 hours were more likely to have low muscle mass, low handgrip strength,and low arm muscle quality (AMQ), and the OR (95%CI) of low appendicular skeletal muscle mass index (ASMI), low total skeletal muscle mass index (TSMI), low grip strength and low AMQ were 1.32 (1.18-1.48),1.26 (1.13-1.41), 1.33 (1.18-1.49) and 1.16 (1.03-1.30), respectively. Compared with participants without insomnia, insomnia patients were more likely to have low muscle mass,and the longer the duration of insomnia,the higher the risk (P for trend <0.001). Participants who reported <6 hours sleep duration and insomnia had a higher proportion of low ASMI and low TSMI,compared with those who slept for 7- hours and without insomnia, the OR (95%CI) were 1.26 (1.08-1.47) and 1.25 (1.07-1.46), respectively. Conclusions: Participants who reported ≥9 hours sleep duration were more likely to have low muscle mass,low handgrip strength,and low AMQ. Participants with insomnia had lower muscle mass, and the longer the duration of insomnia, the higher the proportion of low ASMI and low TSMI.

The correlation of physical activity and sedentary leisure time with low muscle mass, strength, and quality in Chinese adults / 中华流行病学杂志

Objective: To explore the relationship of physical activity and sedentary leisure time with muscle mass, strength, and quality in Chinese adults. Methods: Based on the second resurvey of China Kadoorie Biobank (CKB) in 2013-2014, logistic regression models were used to analyze the correlation of physical activity and sedentary leisure time with low muscle mass, grip strength, and muscle quality. Results: A total of 24 245 participants were included in the analysis. The average daily physical activity level was (18.3±13.8) MET-h/d, and the sedentary leisure time was (4.4±1.9) hours. We took the lowest physical activity quartile as the reference and found that the participants' physical activity was negatively correlated to low muscle mass, strength, and quality. The ORs (95%CIs) of low appendicular skeletal muscle mass index (ASMI), low total skeletal muscle mass index (TSMI), low grip strength and low arm muscle quality (AMQ) were 0.68 (0.60-0.77), 0.66 (0.58-0.75), 0.82 (0.72-0.94) and 0.84 (0.74-0.95), respectively. The subtypes of physical activity, including those related to work, transportation, housework, and leisure, also showed negative correlations with low muscle mass, strength, and quality to varying degrees. Compared with participants with the shortest sedentary leisure time, those who had the longest were more likely to have low TSMI (OR=1.13, 95%CI: 0.99-1.30). Conclusions: Physical activity was negatively correlated with a lower risk of low muscle mass and strength, while longer sedentary leisure time positively correlated with low muscle mass.

Application and research progress of tear proteomics analysis in ocular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Tears are secreted by lacrimal and accessory lacrimal glands, mainly through eyelid and blink movement to form the watery layer of tear film. Tear proteomics is a difficult and hot topic whose main purpose is to detect high sensitive and specific biomarkers representing eye diseases or even systemic diseases so as to facilitate diseases diagnosis and assessment, as well as to achieve personalized treatment, improve prognosis, and design targeted follow-up experiments to understand the molecular mechanisms of the disease. It may have wider application prospects in eye diseases and some systemic diseases compared to existing routine fluid examinations such as blood, urine, and cerebrospinal fluid tests. Numerous studies have shown that many diseases have changes in the composition of tears. In this paper, we will review the progress of proteomics used to investigate the changes of the protein components of tears in different eye diseases.

Levels of skeletal muscle mass and handgrip strength in adults from 10 regions of China / 中华流行病学杂志

Objective@#To describe the regional and population-related differences in skeletal muscle mass and handgrip strength across the 10 regions of China.@*Methods@#24 533 participants aged 38-88 years from the second resurvey of China Kadoorie Biobank were included in our analyses. Appendicular and trunk skeletal muscle mass were assessed using the bioelectrical impedance analysis (TANITA). Handgrip strength was measured using Jamar hand-held dynamometer. Low muscle mass and low muscle strength were defined as the lowest quintile of height-adjusted appendicular muscle mass or handgrip strength according to the Consensus Report of the Asian Working Group for Sarcopenia. We analyzed the mean value of absolute muscle mass, height-adjusted muscle mass, weight-adjusted muscle mass and handgrip strength. We also reported the prevalence of low muscle mass and low muscle strength.@*Results@#The average appendicular and total skeletal muscle mass were (22.0±0.02) kg and (49.7±0.05) kg in men, which were higher than in women [(15.9±0.02) kg and (37.2±0.04) kg, respectively]. The handgrip strength was (32.6±0.06) kg in men, which was higher than (19.9±0.05) kg in women. The absolute muscle mass was higher in north area and urban region (P<0.001). The weight-adjusted muscle mass showed reverse patterns of regional difference compared with height-adjusted muscle mass. Both muscle mass and handgrip strength decreased by age (trend P<0.001), with a larger decline observed in handgrip strength. According to AWGS criteria, the proportions of low muscle mass and strength increased by age. Among participants over 80 years old, the prevalence of low muscle mass and strength were 56.2% and 74.5% in men, and 35.7% and 66.0% in women.@*Conclusions@#Levels of skeletal muscle mass and strength varied greatly among people from 10 regions and among participants with different demographic characteristics. The prevalence of low muscle mass and strength was extremely high in elderly.

Identification of Illicium difengpi and Its Fake I. jiadifengpi Using DNA Barcoding / 中国实验方剂学杂志

Objective:To evaluate and compare the identification of several DNA barcoding candidate sequences on Illicium difengpi and its fake I. jiadifengpi. Method:Samples from different origins of I. difengpi and I. jiadifengpi, were collect extraction of total DNA,nuclear gene ITS2 sequence,chloroplast rbcL,matK gene sequence were selected for PCR amplification,product purification and sequencing,and CondonCode Aligner V3.7.1 was used to proofread stitching. Result:PCR amplification and sequencing of rbcL sequences of I. difengpi and I. jiadifengpi were not satisfactory. It is assumed that their rbcL sequences were too long with slow evolution,which was unsuitable for interbreeding. The success rate of matK sequencing of I. difengpi and I. jiadifengpi was 0 and 76.8%,which may be because primer standards were different for matK sequences of different groups. The results of PCR amplification and sequencing of ITS2 on I. difengpi and I. jiadifengpi were successful,with the success rate of sequencing was 89.3% and 91.2%. Analysis sequencing results, the total length of ITS2 sequences was 268 bases,and there were 2 variation sites of I. difengpi. The total length of ITS2 sequences was 430 bases,and there were 4 or 3 variation sites of I. jiadifengpi. It shows that ITS2 sequences of I. difengpi and I. jiadifengpi were short and has obvious variability and can be amplify,that ITS2 sequence was better than rbcL and matK sequence in molecular identification of I. difengpi and I. jiadifengpi. Conclusion:DNA barcoding based on ITS2 sequence was a powerful and efficient tool for identification of I. difengpi and its fake I. jiadifengpi.

Berberine prevents steatotic liver ischemia reperfusion injury by inhibiting endoplasmic reticulum stress and autophagy / 中华器官移植杂志

Objective To explore the effect of berberine (BBR) on steatotic liver ischemia reperfusion injury and analyze the role of endoplasmic reticulum stress and autophagy .Methods Thirty-four Wistar rats were fed with a high-fat diet for 12 weeks and 2 rats were randomly selected after 8 weeks to observe pathological changes and confirm the model of steatotic liver successfully .Then before opening and closing abdominal cavity ,32 rats were divided into I/R group (normal saline was intragastrically 4 weeks before performing cold I/R treatment) ,BBR group (normal saline was replaced by BBR ,BBR was intragastrically at a dose of 300 mg·kg-1 ·d-1 weeks and others were the same as I/R group) and TG group (TG was intraperitoneally at a dose of 0 .2 mg·kg-124h pre-operation and others were the same as BBR group ) .Then the rats were sacrificed at 6h post-reperfusion .Blood samples were collected from inferior vena cava and hepatic tissues harvested .The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected ,histopathologic changes observed by Hematoxylin & Eosin (HE) staining ,oxidative stress and inflammation determined by ELISA kit and the expressions of p-PERK ,CHOP ,Bip ,LC3 ,Beclin-1 and p62 detected by Western blot .Results As compared with Sham group ,the serum levels of ALT and AST were significantly higher in I/R ,BBR and TG groups (P < 0 .05) .And hepatic histological changes were severe and oxidative stress increased in parallel with the enhancement of pro-inflammation (P< 0 .05) .In BBR group ,the level of hepatic enzymes declined ,liver injury was milder ,oxidative stress decreased and pro-inflammation was lesser compared with I/R and TG groups (P< 0 .05) .Additionally ,as compared with sham group ,the expressions of p-PERK ,CHOP ,Bip ,LC3 ,Beclin-1 and p62 were up-regulated in I/R and BBR groups (P < 0 .05) .TG group increased the levels of LC3 ,Beclin-1 and p62 (P< 0 .05) .Interestingly ,compared with I/R group ,BBR pretreatment down-regulated the expressions of p-PERK ,CHOP ,Bip ,LC3 ,Beclin-1 and p62 (P< 0 .05) .TG group had the higher expressions of LC3 ,Beclin-1 and p62 than those of BBR group (P< 0 .05) .Conclusions BBR pretreatment can protect steatotic liver ischemia reperfusion injury .And the mechanisms may be attributed to the inhibitions of endoplasmic reticulum stress and autophagy .

Effect of berberine on fatty liver ischemia-reperfusion injury in rats: the relationship with endoplasmic reticulum stress in liver tissues / 中华麻醉学杂志

Objective To evaluate the effect of berberine on fatty liver ischemia-repeffusion (I/R) injury and the relationship with endoplasmic reticulum stress in liver tissues.Methods Thirty-two male Wistar rats,aged 4 weeks,weighing 100-150 g,were divided into 4 groups (n=8 each) using a random number table method:control group (group C),fatty liver group (group FL),I/R group and berberine group (group BBR).Rats were fed a normal fat diet for 12 weeks,normal saline 3.5 ml was given intragastrically for 4 weeks starting from 9th week,and rats only underwent simple laparotomy in group C.Rats were fed a high-fat diet (45％ energy originating from fat) for 12 weeks,and the other treatments were similar to those previously described in group C.Rats were fed a high-fat diet (45％ energy originating from fat) for 12 weeks,normal saline 3.5 ml was given intragastrically for 4 weeks starting from 9th week,and then the model of liver I/R injury was established in group I/R.Rats were fed a high-fat diet (45％ energy originating from fat) for 12 weeks,berberine solution (300 mg/kg) 3.5 ml was given intragastrically for 4 weeks starting from 9th week,and then the model of liver I/R injury was established in group BBR.Hepatic ischemia was induced by clamping the portal vein,hepatic artery,right gastric vein,and supra-and inferior-hepatic vena cava to perform cold perfusion with 4 ℃ lactated Ringer's solution lasting for 30 min,followed by reperfusion.The serum triglyceride (TG) concentrations were determined after 4,8 and 12 weeks of diet.Blood samples were collected at 6 h of reperfusion for measurement of serum aspartate transminase (AST) and alanine transaminase (ALT) concentrations.Livers were removed after blood sampling at 6 h of reperfusion and liver tissues were obtained and stained with oil red O and haematoxylin and eosin for examination of pathological changes and for determination of the expression of Bip,CCAAT/enhancer-binding protein homologous protein (CHOP),protein kinase RNA-like endoplasmic reticulum kinase (PERK) and phosphorylated PERK (p-PERK) (by Western blot).p-PERK/PERK ratio was calculated.Results Compared with group C,the serum TG,ALT and AST concentrations were significantly increased,the expression of Bip and CHOP was up-regulated,p-PERK/PERK ratio was increased (P＜0.05),lipid deposition was increased,and liver steatosis was found in group FL.Compared with group FL,the serum AST and ALT concentrations were significantly increased,the expression of Bip and CHOP was up-regulated,pPERK/PERK ratio was increased (P＜0.05),and the pathological changes of liver tissues were accentuated in group I/R.Compared with group I/R,the serum TG,ALT and AST concentrations were significantly decreased,the expression of Bip and CHOP was down-regulated,p-PERK/PERK ratio was decreased (P＜ 0.05),lipid deposition was reduced,and the pathological changes of liver tissues were significantly attenuated in group BBR.Conclusion Berberine can ameliorate fatty liver I/R injury,and the mechanism may be related to inhibiting endoplasmic reticulum stress in liver tissues of rats.

Effect on immune factors and serum CA125 in patients of threatened abortion in early pregnancy complicated with subchorionic hematoma treated with auricular acupuncture combined with dydrogesterone / 中国针灸

OBJECTIVE@#To evaluate the therapeutic effect of auricular acupuncture combined with dydrogesterone for threatened abortion in early pregnancy complicated with subchorionic hematoma.@*METHODS@#A total of 80 patients were randomized into an observation group and a control group, 40 cases in each one. In the control group, dydrogesterone was taken orally twice a day, 10 mg a time until 12-week into pregnancy. In the observation group，auricular acupuncture was applied at penqiang (TF), pizhixia (AT), shen (CO), xin(CO), gan (CO), jiaogan (AH) and neifenmi (CO) on the basis of the control group, the auricular points on both sides were used alternatively. The auricular points were replaced every 3 days with 1 day break, totally 3 weeks (20 days) were required. Before treatment and after 10, 20 days of treatment, the percentage of helper T lymphocyte (Th) and inhibitory T lymphocyte (Ts), ratio of Th and Ts and serum level of CA125 were compared in the two groups. The areas of subchorionic hematoma and gestational sac were evaluated by B ultrasound. The therapeutic effect in the two groups were compared.@*RESULTS@#The effective rate in the observation group was 80.0% (32/40), which was superior to 65.0% (26/40) in the control group (<0.05). After 10, 20 days of treatment, the percentage of Th and ratio of Th and Ts were lower than before treatment, the percentage of Ts were increased in the two groups (<0.01). After 20 days of treatment, the percentage of Th and ratio of Th and Ts in the observation group were lower than the control group (<0.01), the percentage of Ts was higher than the control group (<0.01). After 10, 20 days of treatment, the serum levels of CA125 were reduced compared before treatment in the two groups (<0.01), and the serum levels of CA125 in the observation group were lower than the control group (<0.01). After 10, 20 days of treatment, the ratio of subchorionic hematoma area and gestational sac area in the observation group was lower than the control group (<0.01).@*CONCLUSION@#Auricular acupuncture combined with dextroprogesterone can improve the effective rate of patients with threatened abortion in early pregnancy complicated with subchorionic hematoma, regulate immune factors, promote the hematoma absorption, and has a better synergistic effect with dextroprogesterone.

Adjuvant therapy of acupoint catgut embedding for threatened abortion after in vitro fertilization-embryo transfer: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effects of acupoint catgut embedding on miscarriage prevention and pregnancy outcome in patients with threatened abortion after in vitro fertilization-embryo transfer (IVF-ET).@*METHODS@#Sixty cases of patients with threatened abortion after IVF-ET were randomly divided into an observation group and a control group, 30 cases in each group. The patients in the control group were treated with intramuscular injection of progesterone (40 mg) once every day, while the patients in the observation group, on the basis of the treatment of control group, were treated with catgut embedding at Geshu (BL 17), Ganshu (BL 18), Shenshu (BL 23), Pishu (BL 20), Weishu (BL 21), Xuehai (SP 10), Diji (SP 8) and Fuliu (KI 7), once every two weeks, six times as a course of treatment. The treatment was given until 12 weeks into pregnancy. The level of serum human chorionic gonadotropin (HCG), estradiol (E) and progesterone (P) before and after treatment was recorded; the TCM syndrome score before and after treatment was compared; the successful pregnancy rate and spontaneous abortion rate after treatment were observed in the two groups.@*RESULTS@#Compared before treatment, the scores of TCM syndrome in both groups were reduced after treatment (both <0.01), and score in the observation group was superior to that in the control group (<0.05). After treatment, the clinical efficacy in the observation group was superior to that in the control group (<0.05). After treatment, the hormone levels (β-HCG, E, P) in both groups were increased steadily; the hormone levels in 6-week pregnancy, 8-week pregnancy and 10-week pregnancy were significantly higher than those in 4-week pregnancy (all <0.05); except the levels of P and β-HCG in 10-week pregnancy, the hormone levels in the observation group were superior to those in the control group (all <0.05). After treatment, the early abortion rate was 16.7% (5/30) in the observation group, which was lower than 33.3% (10/30) in the control group (<0.01); the pregnancy rate was 96.0% (24/25) in the observation group, which was higher than 80.0% (16/20) in the control group (<0.01).@*CONCLUSION@#Acupoint catgut embedding is effective for preventing threatened abortion, which could significantly reduce the spontaneous abortion rate, improve the pregnancy success rate, regulate hormone levels in patients after IVF-ET.

Effect of Damaging Rare Mutations in Synapse-Related Gene Sets on Response to Short-term Antipsychotic Medication in Chinese Patients With Schizophrenia: A Randomized Clinical Trial.

Importance: The underlying mechanism for individual differences in patient response to antipsychotic medication remains unknown. Objective: To discover genes and gene sets harboring rare variants associated with short-term antipsychotic medication efficacy. Design, Setting, and Participants: In this multicenter, open-label, randomized clinical trial conducted between July 6, 2010, and December 31, 2011, 3023 patients recruited in China of Chinese Han descent with schizophrenia with total Positive and Negative Syndrome Scale (PANSS) score ≥ 60 received a 6-week treatment of antipsychotic medications randomly chosen from 5 atypical and 2 typical antipsychotic medications. Whole-exome sequencing (WES) was performed in 316 participants (grouped into those with the best response [n=156] and those who had no response [n=160] to the antipsychotic medication prescribed), according to the total PANSS score reduction rate after 6 weeks of treatment. Validation was performed using targeted sequencing in an independent sample of 1920 patients. Data analyses was performed between March 15, 2016, and March 1, 2017. Main Outcomes and Measures: Drug efficacy at week 6 was assessed according to the change in PANSS scores from baseline. Extremely good and extremely poor responders were selected for an initial WES association study, from which a subset of genes showing putative association was selected for independent replication with a targeted sequencing approach. Results: Of the 3023 patients (1549 [51.24%] female and 1474 [48.8%] male; mean [SD] age, 31.2 [7.9] years), 2336 (77.3%) were eligible for genetic analysis. After quality-control exclusions, 316 patients (10.5%) were included for WES and 1920 (63.5%) were included for replication. In the WES discovery stage, 2 gene sets (reduced NMDA [N-methyl-D-aspartate]-mediated synaptic currents and reduced AMPA [α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid]-mediated synaptic currents) were found to be enriched with rare damaging variants in the nonresponder group, suggesting the involvement of these gene sets in antipsychotic medication efficacy. Reduced NMDA-mediated synaptic currents gene set was further replicated in an independent sample using targeting sequencing. No statistically significant differences in antipsychotic drug response were found among the patients who received different antipsychotic drugs. Conclusions and Relevance: Genetic variation in glutamatergic or NMDA neurotransmission is implicated in short-term antipsychotic medication efficacy; WES may have utility in the study of rare genetic variation in pharmacogenetics. Trial Registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934.

Prognosis of post-transplant diabetes mellitus in recipients with steatotic donor livers / 中华肝胆外科杂志

Objective To study the risk factors and prognosis of post-transplant diabetes mellitus (PTDM) in recipients with steatotic donor livers.Method The clinical data of 182 patients who underwent liver transplantation from donors with liver steatosis in Tianjin First Central Hospital from June 2002 to December 2010 were retrospectively analyzed.There were sixteen patients with PTDM and one hundred sixtysix without PTDM.The clinical data of these patients were compared and the risk factors were evaluated by COX regression analysis.The 1-,3-,5-year cumulative survival rates were analyzed after liver transplantation.Result The variables which included sex,pretransplant serum creatinine level,model for end-stage liver disease (MELD) score,intraoperative red blood cell transfusion,and post-transplant biliary complications were significantly different between the two groups.Multivariate Cox regression analysis showed that living-donor,pretransplant fasting blood glucose and post-transplant biliary complications could affect the survival time of patients in PTDM group.The 1-,3-and 5-year cumulative survival rates in the PTDM group were 81.3％,68.8％ and 62.5％,which were significantly lower than those in the non-PTDM group (95.2％,86.1％ and 80.7％ respectively,P ＜ 0.05).Conclusions Living-donation,pretransplant fasting blood glucose and post-transplant biliary complications had a worse prognosis in the PTDM group.A comparatively better long-term survival after liver transplantation can be achieved by reducing the risk factors and the occurrence of PTDM.

Epidemiological characteristics of household fuel use in 10 areas of China / 中华流行病学杂志

Objective To describe the characteristics of cooking and heating fuel use in participants from the China Kadoorie Biobank (CKB) study.Methods The CKB study recruited 512 891 adults from 10 areas in China during 2004-2008.Information on cooking fuel and heating fuel was collected using a questionnaire in baseline survey.The proportions of various fuels used in different areas,in different populations,and at different time points were calculated and compared.Results Overall,52.1％ participants used solid fuel for cooking or heating.Rural areas had higher prevalence of solid fuel use than urban areas.The percentage of participants using solid fuel for cooking was 36.1％ (coal 20.1％,wood/charcoal 16.0％);The percentage of participants using solid fuel for heating was 36.7％ (coal 22.7％,wood/charcoal 14.0％).The prevalence of solid fuel use and the fuel type mainly used varied widely across 10 areas.The proportion of clean fuel use was lower in less-educated and lower-income people.Household coal and wood/charcoal use showed a declining trend,which was more remarkable in urban areas.Conclusion There are still a large number of rural residents and people with low income relying on solid fuel in China,which is a serious public health concern.

Levels of calcaneus bone mineral density in adults from 10 regions of China / 中华流行病学杂志

Objective To describe the regional and population-related differences in calcaneus bone mineral density (BMD) across ten regions of China.Methods Based on the results from the second Re-survey of China Kadoorie Biobank project,in which 5％ of the surviving participants were interviewed during 2013-2014 and 24 677 participants aged 38-87 years were included in the study.We excluded those people with missing data for BMD and important variables.Calcaneus BMD was measured using the quantitative ultrasound bone densitometer.We analyzed four indexes,including broadband ultrasound attenuation (BUA),speed of sound (SOS),stiffness index (SI),and T score.Results The average calcaneus BMDs of the present population were:BUA (109.7 ± 12.6) dB/MHz,SOS (1 554.7 ± 45.6) m/s,SI (88.3 ± 18.8),T score (-0.74 ± 1.28).Urban residents showed higher calcaneus BMD,so as in men.The calcaneus BMD decreased by age,with a larger decline seen in women.Current smokers and postmenopausal women presented lower calcaneus BMD,while in those who frequently drank milk or yogurt or being physically more active,had higher calcaneus BMD.Conclusion Calcaneus BMD varied greatly among people from the ten regions of CKB study and among participants having different demographic characteristics,lifestyle behaviors or health conditions.

Epidemiological characteristics of household fuel use in 10 areas of China / 中华流行病学杂志

Objective To describe the characteristics of cooking and heating fuel use in participants from the China Kadoorie Biobank (CKB) study.Methods The CKB study recruited 512 891 adults from 10 areas in China during 2004-2008.Information on cooking fuel and heating fuel was collected using a questionnaire in baseline survey.The proportions of various fuels used in different areas,in different populations,and at different time points were calculated and compared.Results Overall,52.1％ participants used solid fuel for cooking or heating.Rural areas had higher prevalence of solid fuel use than urban areas.The percentage of participants using solid fuel for cooking was 36.1％ (coal 20.1％,wood/charcoal 16.0％);The percentage of participants using solid fuel for heating was 36.7％ (coal 22.7％,wood/charcoal 14.0％).The prevalence of solid fuel use and the fuel type mainly used varied widely across 10 areas.The proportion of clean fuel use was lower in less-educated and lower-income people.Household coal and wood/charcoal use showed a declining trend,which was more remarkable in urban areas.Conclusion There are still a large number of rural residents and people with low income relying on solid fuel in China,which is a serious public health concern.

Levels of calcaneus bone mineral density in adults from 10 regions of China / 中华流行病学杂志

Objective To describe the regional and population-related differences in calcaneus bone mineral density (BMD) across ten regions of China.Methods Based on the results from the second Re-survey of China Kadoorie Biobank project,in which 5％ of the surviving participants were interviewed during 2013-2014 and 24 677 participants aged 38-87 years were included in the study.We excluded those people with missing data for BMD and important variables.Calcaneus BMD was measured using the quantitative ultrasound bone densitometer.We analyzed four indexes,including broadband ultrasound attenuation (BUA),speed of sound (SOS),stiffness index (SI),and T score.Results The average calcaneus BMDs of the present population were:BUA (109.7 ± 12.6) dB/MHz,SOS (1 554.7 ± 45.6) m/s,SI (88.3 ± 18.8),T score (-0.74 ± 1.28).Urban residents showed higher calcaneus BMD,so as in men.The calcaneus BMD decreased by age,with a larger decline seen in women.Current smokers and postmenopausal women presented lower calcaneus BMD,while in those who frequently drank milk or yogurt or being physically more active,had higher calcaneus BMD.Conclusion Calcaneus BMD varied greatly among people from the ten regions of CKB study and among participants having different demographic characteristics,lifestyle behaviors or health conditions.

Enhanced B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation contributes to ABCC1-mediated chemoresistance and glutathione-mediated survival in acquired topoisomerase II poison-resistant cancer cells.

Nuclear factor erythroid-2-related factor 2 (NRF2) mainly regulates transcriptional activation through antioxidant-responsive elements (AREs) present in the promoters of NRF2 target genes. Recently, we found that NRF2 was overexpressed in a KB-derived drug-resistant cancer cell panel. In this panel, KB-7D cells, which show acquired resistance to topoisomerase II (Top II) poisons, exhibited the highest NRF2 activation. To investigate whether NRF2 directly contributed to acquired resistance against Top II poisons, we manipulated NRF2 by genetic and pharmacological approaches. The result demonstrated that silencing of NRF2 by RNA interference increased the sensitivity and treatment with NRF2 activator decreased the sensitivity of KB and KB-7D cells toward Top II poisons. Further, increased B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation activated NRF2 signaling in KB-7D cells. Moreover, increased binding of NRF2 to an ARE in the promoter of ATP-binding cassette subfamily C member 1 (ABCC1) directly contributed to Top II poison resistance. In addition, activation of NRF2 increased glutathione level and antioxidant capacity in KB-7D cells compared with that in KB cells; moreover, high glutathione level provided survival advantage to KB-7D cells. Our study is the first to show that aberrant NRF2 activation is via increased B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation, which increases the acquired resistance and promote the survival of Top II poison-resistant cancer cells. Importantly, NRF2 downstream effectors ABCC1 and glutathione directly contribute to acquired resistance and survival, respectively. These results suggest that blockade of NRF2 signaling may enhance therapeutic efficacy and reduce the survival of Top II poison-refractory tumors in clinical.