Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16α-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR-FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

OBJECTIVE To provide reference and suggestions for dynamic adjustment of classification management lists for clinical use of antibiotics and the promotion of rational use of antibiotics. METHODS The latest version of provincial classification management lists for clinical use of antibiotics were aggregated into the “national list”， which was compared with 2021 WHO AWaRe classification list of antibiotics （hereinafter referred as to “AWaRe classification list”） to make a descriptive statistical analysis about the number of different classes of antibiotics in the two lists and their differences. RESULTS Based on the different classification principles， 262 kinds of antibiotic preparations in the national list were classified into non-restricted （84）， restricted （83） and highly-restricted classes （95）， and 258 kinds in the AWaRe classification list were classified into access （87）， watch （142） and reserve classes （29）； 182 kinds of antibiotic preparations were both included in the two lists. In the national list， among the non-restricted antibiotic preparations， 36 kinds belonged to access class， 30 belonged to watch class and 1 belonged to reserve class； among restricted antibiotic preparations， 7 belonged to access class， 46 kinds belonged to watch class and 3 belonged to reserve class； among highly-restricted antibiotic 82805019。E-mail：yyy211anne@163.com preparations， 9 belonged to access class， 35 belonged to watch class and 15 kinds belonged to reserve class. Among them， 91 kinds of antibiotic preparations were not recommended by WHO （20 kinds） or not included in the AWaRe classification list （71 kinds）. CONCLUSIONS The classification methods of two lists are different in classification principles and grading of some similar drugs. The classification management list of antibiotics is one of the key points of antibiotics management， more research is needed in the future to provide sufficient evidence for optimizing antibiotics classification management.

OBJE CTIVE To inv estigate the antibiotic use and rationality for children in community health service institutions from Beijing ，and to provide reference for promoting rational use of antibiotics in primary healthcare institutions. METHODS All the prescriptions for children from primary healthcare institutions in 2019 were extracted from prescription review system of community health service institutions in Beijing. The use of antibiotics was described according to the related indicators of the World Health Organization/International Network for Rational Use of Drug （WHO/INRUD）. The structure of antibiotics use was analyzed according to the anatomical therapeutic chemical （ATC）classification as well as the WHO AWaRe classification and diagnosis. RESULTS A total of 288 primary healthcare institutions and 10 422 prescriptions for children were included. The number of institutions in high-income areas ，middle-income areas and low-income areas were 119，80 and 89 respectively，and the number of prescriptions involved were 2 430，2 163 and 5 829 respectively，including 1 447 prescriptions involving antibiotics （13.9％）. Among 1 447 prescriptions，the rate of prescriptions involving combined use of antibiotics was 1.4％（20 pieces）；the rate of prescriptions involving antibiotics injection was 9.7％（141 pieces）；4.8％ antibiotics prescriptions were rated as unreasonable （69 pieces）. The three most commonly used antibiotics were the macrolides （40.2％），the second-generation cephalosporins （26.5％） and the third-generati on cephalosporins （23.4％）. The proportion of antibioti cs prescriptions from groups of access ，caution， reserve and not recommended were 9.1％，92.1％，0.3％，and 0， respectively. The rate of antibiotics prescriptions fortonsillitis was the highest （31.9％ ）. Among 69 irrationalantibiotics prescriptions ，main of them were irrational drug use （56 pieces，81.2％）. CONCLUSIONS The rate of antibiotics prescriptions for children in primary healthcare institutions from Beijing is lower than the standard of WHO antibiotics prescription rate （20.0％-26.8％），but the use rate of antibiotics at caution grade is too high.

OBJECTIVE：To provide re ference for scientific management and rational use of antibiotics. METHODS ：Provincial antibiotic classification management lists were retrieved from official websites of provincial health administrative departments ， CNKI and other search engines from Apr. 2012 to Mar. 2020. The difference and adjustment of those lists were analyzed descriptively. RESULTS & CONCLUSIONS ： Since April 2012， 30 provinces released provincial antibiotic classification management lists ，among which only 10 provinces updated the lists. In the provincial classification management lists ，the list of Jiangsu included the most antibiotics （208 kinds），that of Xinjiang involved the least （101 kinds）. Among the 253 antibiotics included in the provincial lists ，134 antibiotics had two management levels ，and 19 antibiotics had three management levels. The 10 antibiotics with the most times of adjustment in the provincial lists mainly include nitimidazoles ，β-lautam compound preparations and quinolones. There was the phenomenon that the same antibiotics were simultaneously included or withdrawn from the lists ，and the grading management level was increased or decreased in the provincial adjustment. Provincial classification management lists updated slowly in China ，and the quantity and classification of drugs selected in the list were quite different. It is suggested that provincial health administrative departments should continuously optimizeand improve classification management list of antibiotics ， and form a long-term mechanism of dynamic adjustment of list and inter-provincial evidence sharing ，so as to promote the rational clinical use of antibiotics ，and curb bacterial resistance.

Objective:To assess the value of 18F-fluorodeoxyglucose (FDG) PET/MR parameters and their changes in predicting and evaluating the curative effect in patients with locally advanced rectal cancer before and after neoadjuvant chemoradiotherapy (NCRT). Methods:From June 2017 to June 2020, 13 patients (9 males, 4 females; age (52.2±13.2) years) with locally advanced rectal cancer confirmed pathologically and underwent NCRT in Chinese PLA General Hospital were retrospectively enrolled. All patients performed the first PET/MR within one month before NCRT and the second PET/MR within one month before operation. PET/MR parameters including maximum standardized uptake value (SUV max), mean standardized uptake value (SUV mean), metabolic tumor volume (MTV) 2.5, total lesion glycolysis (TLG), minimum apparent diffusion coefficient (ADC min), and their changing percentage (Δ) before and after NCRT were collected. Patients were divided into pathologically complete remission (pCR) group and non-pCR group or response group and non-response group according to the postoperative pathological results as the gold standard. Mann-Whitney U test and logistic regression analysis were used for data analysis. The cut-off values of related parameters and their diagnostic efficiencies were determined by receiver operating characteristic (ROC) curve analysis. Results:Of 13 patients, 5 reached pCR and 8 had histological reaction (response). There were no significant differences in parameters (SUV max, SUV mean, MTV 2.5, TLG, ADC min) between different groups before treatment ( U values: 8.00-19.00, all P>0.05). There were significant differences in SUV max, SUV mean, MTV 2.5, TLG and ΔADC min between pCR group and non-pCR group after treatment ( U values: 0.00-6.00, all P<0.05), but only SUV max was correlated with pCR after treatment (odds ratio ( OR)=0.335, 95% CI: 0.123-0.917, P=0.033). The area under curve (AUC) was 0.95 and the cut-off value of SUV max was 3.055, with the sensitivity of 100%, the specificity of 80.0% and the accuracy of 92.3%. There were significant differences in SUV max, SUV mean, TLG, ADC min, ΔSUV max and ΔADC min between the response group and non-response group after treatment ( U values: 0.00-6.00, all P<0.05), but only ΔSUV max was correlated with the response results ( OR=2.022, 95% CI: 1.100-4.130, P=0.048). The AUC was 0.90 and the cut-off value of ΔSUV max was 69.0%, with the sensitivity of 87.5%, the specificity of 80.0% and the accuracy of 84.6%. Conclusions:PET/MR has high accuracy in evaluating NCRT for locally advanced rectal cancer. SUV max is an independent predictor of pCR after treatment, while ΔSUV max is an independent predictor of histological reaction (response).

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we conducted chronic salt loading and potassium supplementation interventions, aiming to examine the association between genetic variants in renalase and blood pressure (BP) responses to dietary interventions of salt and potassium intake. 【Methods】 In 2004, 514 subjects from 126 families were recruited in Shaanxi Province to establish the salt-sensitive hypertension study cohort. Among them, 334 non-parent subjects were selected and sequentially maintained on a low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Ten single nucleotide polymorphisms (SNPs) in the renalase gene were genotyped on the MassARRAY platform. 【Results】 SNP rs2576178 of the renalasegene was significantly associated with systolic BP (SBP) and mean arterial pressure (MAP) responses to low-salt intervention (SBP: β=-2.730, P<0.05; MAP: β=-1.718, P<0.05). In addition, SNP rs12356177 was significantly associated with diastolic BP response to low-salt diet (β=-1.608, P<0.05). However, we did not find any association for the renalase SNPs with BP response to high-salt diet with potassium supplementation reached nominal statistical significance. 【Conclusion】 Genetic variants in renalase gene are significantly associated with BP response to low-salt diet, suggesting that renalase may be mechanistically involved in BP salt-sensitivity.

OBJECTIVE：To provide scientific basis for evaluating the burden caused by antibiotic resistance （AbR）and reference for policy making on crubing AbR in China. METHODS ：Databases including CNKI ，Wanfang database ，VIP，PubMed， Scopus，Medline and EconoLite from Jan. 1st 2016 to Aug. 10th 2020 were searched to collect studies on burden caused by AbR in China . After independent literature screening anddata extraction ，Newcastle-Ottawa scale （NOS）was used to evaluate the literature quality ，and a descriptive analysis was conduced to evaluate the health and economic burden caused by AbR. RESULTS ：A total of 27 Chinese and English literatures were included. The NOS scores of i ncluded literatures were 4-6，and all of them were retrospective case-control study ； the patients were divided into case group （resistance infection ） and control group （susceptible infection or non-infection ）； mortality，length of stay and medical expenditure were commonly applied as the measurement indexes. In the included studies ，the mortality of patients infected with AbR bacteria was 0.7-12.0 times that of patients infected with susceptible bacteria ；the mean or medium value of total length of stay was 0.9-2.5 times that of patients infected with susceptible bacteria ；the mean or medium of total medical expenditure was 1.0-2.7 times that of patients with susceptible bacteria infection. The differences in these indicators were greater between patients infected with AbR infections and those without becterial infections. CONCLUSIONS ：Bacterial drug resistance could increase the health and economic burden. However ，the existing relevant studies were mainly single center researches，the sample representation was insufficient ；the research design did not adjust for time-dependent bias ；the repeatability was low ，and the perspective of evalution was limited. It is urgent to carry out multicenter studies with higher quality to comprehensively evaluate the health and economic burden caused by AbR in China.

Obesity has become one of the most serious issues threatening the health of humankind, and we conducted this study to examine whether and how celastrol protects against obesity.

Objective To investigate the clinical significance of plasma methylated Septin 9 (SEPT9)gene test for colorectal cancer(CRC).Methods Clinical data of this retrospective study were obtained from Huashan Hospital of Fudan University(2016-2017).The subjects were divided into three groups,84 patients in CRC group,50 patients with adenoma in precancerous group,and 20 cases as healthy controls.A fluorescent PCR assay was used to analyze SEPT 9 methylation in DNA extracted from plasma. Chi square test was used for statistical analysis.Results The positive incidence of SEPT9 gene methylation in plasma was 63.1%(53/84)in CRC group,significantly higher than 10%(5/50)in precancerous group (χ2=35.993, P<0.001), and undetectable in healthy group.The sensitivity of the methylated SEPT9 gene test was 63.1%(53/84), and the sensitivity of a joint detection combined with carcinoembryonic antigen(CEA)was 75%(63/84).The receiver operating characteristic curve(ROC)showed that methylated SEPT9 gene test had 0.828 in the area under the curve(AUC),higher than 0.795 in the AUC of CEA test.In CRC patients,51.4%(19/37)in the stage Ⅰ-Ⅱand 72.3%(34/47)in the stage Ⅲ-Ⅳ were positive for methylated SEPT9 gene test(χ2=3.917, P<0.05).There were no significant differences in gender,age and primary tumor site.Conclusion The SEPT9 gene methylation in plasma is helpful for early screening for CRC,and is associated with CRC progression.