ObjectiveTo explore the impact of Gegen Qinliantang（GQT） on the fecal short-chain fatty acids（SCFAs） metabolism in antibiotic-associated diarrhea（AAD） through targeted metabolomics. MethodA total of 240 SD rats were randomly divided into six groups（n=40， half male and half female）， including blank group， model group， bifidobiogen group（0.15 g·kg^-1）， and GQT high-， medium-， and low-dose groups（10.08， 5.04， 2.52 g·kg^-1）， except for the blank group， clindamycin（250 mg·kg^-1） was given to all groups by gavage for modeling every day for 7 d. After successful modeling， each administered group was gavaged with the corresponding dose of the drug， and the blank and model groups were gavaged with an equal volume of normal saline solution， 1 time/d， for 14 d. At 0， 3， 7， 14 d after the drug intervention， eight rats were randomly selected from each group， respectively. Gas chromatography-time-of-flight mass spectrometry（GC-TOF-MS） was used to perform targeted metabolomic analysis of SCFAs in the feces of rats， and partial least squares-discriminant analysis（PLS-DA） was applied to compare the differences in metabolic profiles between groups at different treatment times， and to compare the changes in the contents of SCFAs in rat feces between groups. ResultPLS-DA results showed that the blank group could be clearly distinguishable from the model group， with GQT exhibiting a closer proximity to the blank group after 7 d of treatment. After further analyzing the composition of SCFAs， it was found that the proportion of acetic acid increased and the proportions of butyric acid， valeric acid， hexanoic acid and isovaleric acid decreased in the model group compared with the blank group. After the treatment with GQT， the proportions of butyric acid， isobutyric acid， valeric acid， and isovaleric acid increased， and the proportions of acetic acid， propionic acid and caproic acid decreased. Subsequent differential analysis revealed that GQT could significantly improve the content of butyric acid， and had a certain retrogressive effect on the contents of valeric acid and hexanoic acid. ConclusionThe medium dose group of GQT can improve the contents of SCFAs in AAD feces after 7 days of treatment， which may be related to the improvement of the composition ratio of SCFAs and the contents of butyric acid， valeric acid and caproic acid.

This study constructed a LHCGR-CRE-luc-HEK293 transgenic cell line according to the activation of the cAMP signaling pathway after recombinant human chorionic gonadotropin binding to the receptor. The biological activity of recombinant human chorionic gonadotropin was assayed using a luciferase assay system. The relative potency of the samples was calculated using four-parameter model. And the method conditions were optimized to validate the specificity, relative accuracy, precision and linearity of the method. The results showed that there was a quantitative potency relationship of human chorinonic gonadotropin (hCG) in the method and it was in accordance with the four-parameter curve. After optimization, the conditions were determined as hCG dilution concentration of 2.5 μg·mL^-1, dilution ratio of 1∶4, cell number of 10 000-15 000 cells/well, and induction time of 6 h. The method had good specificity, relative accuracy with relative bias ranging from -8.9% to 3.4%, linear regression equation correlation coefficient of 0.996, intermediate precision geometric coefficient of variation ranging from 3.3% to 15.0%, and linearity range of 50% to 200%. This study successfully established and validated a reporter gene method to detect hCG biological activity, which can be used for hCG biological activity assay and quality control.

Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.

ObjectiveTo investigate the correlation of polymorphism and loci interaction of nucleic acid binding oligomeric domain-like receptor heat protein domain associated protein 3 (NLRP3) gene and susceptibility to coal workers' pneumoconiosis (CWP) in Xinjiang Region. Methods A total of 109 CWP were selected as the case group, and 69 coal miners with similar age, years of dust exposure and work types were selected as the control group by convenient sampling method. Blood samples of individuals in workers in these two groups were collected, and the genotypes of single nucleotide polymorphism loci, rs1539019, rs4612666, rs4925650 and rs7525979, in the NLRP3 gene were detected using an improved multiplex ligation detection reaction. The optimal genetic model was selected based on the Akaike information criterion. Results The results of unconditional logistic regression analysis showed that individuals with the C allele of rs1539019 or rs4612666 had a higher risk of CWP than those with the A or T allele (all P<0.05), and individuals with the AA genotype of rs1539019 or the TT genotype of rs4612666 had a lower risk of CWP than those with the CC genotype (all P<0.05), after adjusting for age, years of work, alcohol, and smoking. The optimal genetic models for rs1539019 and rs4612666 were the recessive model and the additive model, respectively, and these differences were associated with the susceptibility to CWP at the Bonferroni-corrected level (all P<0.05). No correlation was found between rs4925650 and rs7525979 and the susceptibility to CWP (all P>0.05). In the smoking population, the rs1539019 co-dominant model, recessive model, and additive model were associated with a decreased risk of CWP (all P<0.05). The rs4612666 co-dominant model, dominant model and additive model were associated with an increased risk of CWP (all P<0.05), with the optimal genetic models being the recessive model and the additive model among smokers. The rs1539019 and rs4612666 were not found to be associated with the increased risk of CWP in non-smokers (all P>0.05). The rs4612666 dominant model and additive model were associated with an increased risk of CWP (all P<0.05), and the rs4925650 recessive model and over-dominant model were associated with a decreased and increased risk of developing CWP (all P<0.05), with the optimal genetic models being the dominant model and the over-dominant model in drinkers. The rs1539019 co-dominant model, dominant model, recessive model, and additive model were associated with a decreased risk of developing CWP (all P<0.05), and the rs4612666 co-dominant model, recessive model, and additive model were associated with an increased risk of developing CWP (all P<0.05), with the optimal genetic models being the additive model and the recessive model in non-drinkers. The result of haplotype analysis showed that the ACAC and ACGC haplotypes were associated with a reduced risk of CWP (all P<0.05). Conclusion The rs1539019 and rs4612666 loci of the NLRP3 gene are associated with susceptibility to CWP. This study provides clues for further research on the risk of CWP in coal workers.

ObjectiveTo explore the rehabilitation outcome of personalized pulmonary rehabilitation therapy in pneumoconiosis patients in the rehabilitation station. Methods A total of 42 pneumoconiosis patients were selected as the study subjects from seven pneumoconiosis rehabilitation stations in Xinjiang Uygur Autonomous Region using the judgment sampling method. Patients were treated with personalized rehabilitation therapy for three months, and the outcome was analyzed. Results The six-minute walking test distance, maximum inspiratory pressure, maximum expiratory pressure, forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and FEV₁/FVC ratio of the pneumoconiosis patients were higher after rehabilitation therapy than those before therapy (all P<0.05). The score of Chronic Obstructive Pulmonary Disease Assessment Test of patients after therapy was lower than that in pre-treatment (P<0.05). There was no significant difference in respiratory difficulty, Borg scale, balance ability, depression symptoms, anxiety symptoms, nutritional status scores, body mass index, blood oxygen saturation, and heart rate before and after rehabilitation therapy (all P>0.05). Conclusion The individualized pulmonary rehabilitation therapy of pneumoconiosis patients at pneumoconiosis rehabilitation station can improve the respiratory muscle strength and lung function of patients, and improve their quality of life.

Objective To analyze the effect of low-dose methylprednone sodium succinate combined with erythromycin in the treatment of Mycoplasma pneumoniae infection with elevated lactate dehydrogenase(LDH)in children.Methods Children with Mycoplasma pneumoniae pneumonia(MPP)complicated with elevated LDH were divided into control group and treatment group by random number table method.The control group was given erythromycin treatment,and the treatment group was given low-dose methylprednisolone sodium succinate combined with erythromycin treatment.Clinical efficacy and clinical symptom disappearance time were recorded in both groups.Pulmonary X-ray signs,immune function[T cell subsets(CD4+,CD8+,CD4+/CD8+)],immunoglobulin(Ig)A,IgM and serum LDH were compared between the two groups before and after treatment,and the adverse drug reactions of treatment were observed.Results There were 51 cases in control group and 51 cases in treatment group.The total effective rate in treatment group was 96.00％,which was significantly higher than 81.63％in control group(P＜0.05).The fever abatement times in treatment group and control group were(4.22±0.87)and(5.46±0.98)d;cough disappearance times were(6.31±0.98)and(7.49±1.10)d;disappearance times of pulmonary rales were(7.36±1.14)and(8.61±1.23)d,all with significant difference(all P＜0.05).After treatment,the patchy infiltrating shadow sign rates in treatment group and control group were 2.00％and 16.33％;the bronchial wall thickening sign rates were 4.00％and 18.37％,all with significant difference(all P＜0.05).After treatment,IgA levels in treatment group and control group were(0.55±0.11)and(0.68±0.12)g·L-1;IgM levels were(0.90±0.19)and(1.18±0.21)g·L-1;LDH levels were(229.45±10.30)and(240.18±11.17)U·L-1,all with significant difference(all P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 6.00％and 4.08％respectively,without significant difference(P＞0.05).Conclusion Erythromycin combined with low-dose methylprednone in systemic treatment of children with MPP and elevated LDH has a significant efficacy,and it can promote the reductions of inflammation and immune disorders and accelerate the disease outcomes,and it is safe and reliable.

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

As a new strategy for the application of sacubitril/valsartan (LCZ696) in patients with CKD, much evidence showed that it improved the prognosis of patients with CKD. This review summarizes the efficacy and safety of sacubitril/valsartan in physiology, pathology, pharmacology and clinical application by searching Wanfang, CNKI, PubMed and other databases for related articles on the application of sacubitril/valsartan in CKD patients. Although LBQ657, the active product of sacubitril, has a high drug accumulation in patients with moderate, severe renal injury, and ESRD, it is not cleared in hemodialysis, and has very little eliminated in peritoneal dialysis, which does not affect its safety. Compared with angiotensin converting enzyme inhibitor and angiotensin receptor blocker drugs, LCZ696 could increase the blood pressure control rate, improve cardiac function, slow down the decline of glomerular filtration rate, and significantly improve cardiovascular outcomes without more adverse events. Sacubitril/valsartan can be used in all levels of CKD patients complicated with hypertension and/or heart failure, with reliable safety and tolerance.

Objective:To investigate the incidence and influencing factors of allergic reactions to cephalosporins.Methods:A cross-sectional study of 29 medical institutions in Zhejiang Province was conducted from April 2021 to June 2021.The incidence of allergic reactions to cephalosporins was investigated,and the influencing factors of cephalosporin-induced allergic reactions were analyzed by Poisson regression.Results:A total of 56 155 patients were included in this study.The total incidence of allergic reactions to cephalosporin was 1.67‰,the highest incidence of anaphylaxis occurred for ceftizoxime(4.27‰),followed by ceftriaxone(3.49‰)and cefotaxime(2.40‰).There was no significant difference in the incidence of allergic reactions between patients with negative skin tests and those without skin tests(1.75％o vs.1.63‰,RR=1.07,95％CI:0.70-1.63,P＞0.05).Poisson regression showed that body mass index(BMI)＜18.5 kg/m2(RR=2.43,95％CI:1.23-4.82,P＜0.05)and history of β-lactam antibiotics allergy(RR=33.88,95％CI:1.47-781.12,P＜0.05)increased cephalosporin-induced anaphylaxis.Compared with cefuroxime,the risk of allergic reactions was increased for ceftriaxone(RR=3.08,95％CI:1.70-5.59,P＜0.01),ceftazidime(RR=1.89,95％CI:1.03-3.47,P＜0.05),and ceftizoxime(RR=3.74,95％CI:1.64-8.50,P＜0.01).Conclusions:Lower BMI and history of β-lactam antibiotics allergy increase the risk of cephalosporin allergic reactions.The routine skin test may not reduce the occurrence of allergic reactions to cephalosporins. This study has been registered at Chinese Clinical Trial Registry(ChiCTR2200064314).

Objective:To explore the risk factors of coal workers' pneumoconiosis, reveal the molecular mechanism of pyroptosis in peripheral blood of coal workers' pneumoconiosis patients, and provide new strategies and potential diagnostic biomarkers for the treatment of the disease.Methods:From January 1, 2020 to December 31, 2022, workers with suspected occupational diseases who were diagnosed with coal workers' pneumoconiosis in the Third People's Hospital of Xinjiang Uygur Autonomous Region were included in the study, including 77 patients with coal workers' pneumoconiosis stage Ⅰ, 10 patients with stage Ⅱ, 6 patients with stage Ⅲ, and 49 workers with dust-free lung disease as the control group. General information of the subjects was collected, blood samples were collected for routine blood and blood biochemical results, and plasma levels of interleukin (IL) -1β and IL-18 were measured. Combined with the results of clinical examination, multi-factor ordered logistic regression analysis was carried out to evaluate the influencing factors of coal workers' pneumoconiosis. At the same time, the expression of pyroptosis related proteins in blood cells was detected to reveal the molecular mechanism of coal workers' pneumoconiosis.Results:All 142 subjects were male, with an average age of (51.65±6.31) years old and an average working age of (15.94±9.38) years. There were significant differences in smoking age ( F=4.95, P=0.003) and lunch break distribution ( H=8.84, P=0.031) among all groups. The hemoglobin content of stage Ⅰ patients was higher than that of stage Ⅱ patients, and the neutrophil percentage of stage Ⅲ patients was higher than that of the other 3 groups ( P<0.05). The levels of total bilirubin and indirect bilirubin in stage Ⅰ patients were higher than those in control group, while the erythrocyte sedimentation rate in stage Ⅱ patients was higher than that in the other 3 groups ( P<0.05). The levels of IL-18 and IL-1β in stage Ⅲ of coal workers' pneumoconiosis were higher than those in the other 3 groups ( P<0.05). Multiple logistic regression analysis showed that smoking age ( OR=1.03, 95% CI: 1.00-1.06) and IL-1β level ( OR=4.61, 95% CI: 1.59-13.32) were independent risk factors for coal workers' pneumoconiosis ( P<0.05). Compared with the control group, the expression levels of nucleotide-binding of oligomeric domain-like receptor protein 3 (NLRP3), Caspase-1, GSDMD, Caspase-4 and other proteins in stage Ⅲ of coal workers' pneumoconiosis were significantly increased ( P<0.05) . Conclusion:Smoking age is a risk factor for coal workers' pneumoconiosis, IL-1β may be a potential biomarker for the diagnosis of coal workers' pneumoconiosis, and pyroptosis may play a role in the development of peripheral inflammation of coal workers' pneumoconiosis.