Objective:To compare the clinical characteristics of patients with drug-induced liver injury (DILI) caused by Polygonum multiflorum and other drug-induced liver injuries (DILI).Methods:A retrospective cohort study was conducted. Clinical data of seventy-three cases confirmedly diagnosed with DILI caused by Polygonum multiflorum, 168 cases diagnosed with DILI caused by other traditional Chinese medicines, and 225 cases diagnosed with DILI caused by modern medicines admitted to Peking University First Hospital, the Fipth People's Hospital of Wuxi, Yantai Qishan Hospital, and Qinhuangdao Third Hospital from January 1995 to August 2019 were selected and collected as the research subjects. The Mann-Whitney U test was used for comparison of skewed distribution of continuous data between two groups. The Kruskal-Wallis rank-sum test was used for comparison between three groups. The χ2 test was used for comparing count data between groups. Results:Among the 73 cases with DILI caused by Polygonum multiflorum, 11 (15.1%) took a single herb of Polygonum multiflorum (including its powder and boiled water), 37 (50.7%) took traditional Chinese patent medicines containing Polygonum multiflorum, and 25 (34.2%) took a traditional Chinese medicine formula containing Polygonum multiflorum. The age of the DILI group caused by Polygonum multiflorum was 48 years old, which was lower than the other two groups (the DILI group caused by other traditional Chinese medicines: 55 years old, the DILI group caused by modern medicines: 52 years old; P<0.01). The levels of alanine aminotransferase (ALT), aspartate aminotransferase, and alkaline phosphatase were all higher than the other two groups ( P<0.05). The proportion of patients with antinuclear antibody positivity rate and severity of liver damage grade 3 was higher in the DILI group induced by Polygonum multiflorum than those in the modern drug-induced DILI group ( P<0.05). The liver cell injury type accounted for 96.6% (57/59) in the DILI group caused by Polygonum multiflorum, which was higher than that in the modern drug-induced DILI group (69.3%, 156/225) ( P<0.001). There was no statistically significant difference ( P>0.05) in gender, age, medication duration, and various biochemical indicators between patients with DILI caused by Polygonum multiflorum monotherapy and compound preparations in terms of compatibility. The ALT level in the DILI group caused by raw Polygonum multiflorum was higher than that in the DILI group caused by processed Polygonum multiflorum [the DILI group caused by raw Polygonum multiflorum: 1 289.0(921.8, 1 851.8)U/L, the DILI group caused by processed Polygonum multiflorum: 890.0(304.0,1 320.0)U/L; P<0.05] according to the comparison of processing methods. Conclusion:The degree of DILI caused by Polygonum multiflorum is more obvious than that caused by other drugs. There was no difference in the degree of DILI caused by the single and the compound formulation. However, the liver damage caused by raw Polygonum multiflorum was more severe than that caused by processed Polygonum multiflorum.

Objective:To compare the clinical characteristics of patients with drug-induced liver injury (DILI) caused by Polygonum multiflorum and other drug-induced liver injuries (DILI).Methods:A retrospective cohort study was conducted. Clinical data of seventy-three cases confirmedly diagnosed with DILI caused by Polygonum multiflorum, 168 cases diagnosed with DILI caused by other traditional Chinese medicines, and 225 cases diagnosed with DILI caused by modern medicines admitted to Peking University First Hospital, the Fipth People's Hospital of Wuxi, Yantai Qishan Hospital, and Qinhuangdao Third Hospital from January 1995 to August 2019 were selected and collected as the research subjects. The Mann-Whitney U test was used for comparison of skewed distribution of continuous data between two groups. The Kruskal-Wallis rank-sum test was used for comparison between three groups. The χ2 test was used for comparing count data between groups. Results:Among the 73 cases with DILI caused by Polygonum multiflorum, 11 (15.1%) took a single herb of Polygonum multiflorum (including its powder and boiled water), 37 (50.7%) took traditional Chinese patent medicines containing Polygonum multiflorum, and 25 (34.2%) took a traditional Chinese medicine formula containing Polygonum multiflorum. The age of the DILI group caused by Polygonum multiflorum was 48 years old, which was lower than the other two groups (the DILI group caused by other traditional Chinese medicines: 55 years old, the DILI group caused by modern medicines: 52 years old; P<0.01). The levels of alanine aminotransferase (ALT), aspartate aminotransferase, and alkaline phosphatase were all higher than the other two groups ( P<0.05). The proportion of patients with antinuclear antibody positivity rate and severity of liver damage grade 3 was higher in the DILI group induced by Polygonum multiflorum than those in the modern drug-induced DILI group ( P<0.05). The liver cell injury type accounted for 96.6% (57/59) in the DILI group caused by Polygonum multiflorum, which was higher than that in the modern drug-induced DILI group (69.3%, 156/225) ( P<0.001). There was no statistically significant difference ( P>0.05) in gender, age, medication duration, and various biochemical indicators between patients with DILI caused by Polygonum multiflorum monotherapy and compound preparations in terms of compatibility. The ALT level in the DILI group caused by raw Polygonum multiflorum was higher than that in the DILI group caused by processed Polygonum multiflorum [the DILI group caused by raw Polygonum multiflorum: 1 289.0(921.8, 1 851.8)U/L, the DILI group caused by processed Polygonum multiflorum: 890.0(304.0,1 320.0)U/L; P<0.05] according to the comparison of processing methods. Conclusion:The degree of DILI caused by Polygonum multiflorum is more obvious than that caused by other drugs. There was no difference in the degree of DILI caused by the single and the compound formulation. However, the liver damage caused by raw Polygonum multiflorum was more severe than that caused by processed Polygonum multiflorum.

Non-obstructive azoospermia (NOA) is a complex male infertility disease with abnormal spermatogenesis. With the wide application of sequencing technology in recent years, key genes related to spermatogenesis in NOA patients have been continuously mined out. Some epigenetic factors, such as DNA methylation, histone changes and non-coding RNAs are important indicators that reflect to the heterogeneity and complexity of spermatogenesis failure in NOA. This article systematically reviewed the latest studies on the key genes and some epigenetic factors during spermatogenesis of NOA, which may prospectively help to exploit clinical biomarker and to optimize therapeutic proposals.

Non-obstructive azoospermia (NOA) is a complex male infertility disease with abnormal spermatogenesis. With the wide application of sequencing technology in recent years, key genes related to spermatogenesis in NOA patients have been continuously mined out. Some epigenetic factors, such as DNA methylation, histone changes and non-coding RNAs are important indicators that reflect to the heterogeneity and complexity of spermatogenesis failure in NOA. This article systematically reviewed the latest studies on the key genes and some epigenetic factors during spermatogenesis of NOA, which may prospectively help to exploit clinical biomarker and to optimize therapeutic proposals.

Objective: To study the correlation between the level of T-bet expression and liver damage in peripheral plasma cells of patients with autoimmune hepatitis (AIH) in order to provide reference for the study of pathogenesis and development of diseases. Methods: The peripheral venous blood and clinical examination data of 29 cases with AIH and 6 healthy volunteers were collected. The percentage of subpopulations of peripheral blood B cells and the proportion of T-bet⁺ cells in each subgroup were detected by flow cytometry. Plasma cells (CD19⁺CD10^-CD27^hiCD38^hi), primary B cells (CD19⁺CD10^-CD27^-IgD⁺), transitional B cells (CD19⁺CD10⁺), and memory B cells (CD19⁺CD10^-CD27⁺IgD^-) were the included subsets of B cells. Serum immunoglobulin G (IgG) and alanine aminotransferase (ALT) levels, the proportion of B cells in peripheral blood subsets and IgG level, the proportion of T-bet⁺ cells in each subset and the proportion of T-bet⁺ plasma cells in each subset in B cells, the proportion of T-bet⁺ plasma cells and the level of serum ALT were analyzed for correlation analysis. Statistical analysis was performed using two independent sample t-tests and linear regression. Results: The serum IgG level of AIH patients with abnormal ALT (19.47 ± 1.039)g/L was significantly higher than that of normal ALT patients (15.5 ± 1.069)g/L, and the difference was statistically significant (t = 2.65, P < 0.05). The percentage of peripheral plasma cells in B cells of AIH patients (2.80 ± 0.14) % was higher than that of healthy volunteers (0.73 ± 0.09) %, and the difference was statistically significant (P < 0.01). The percentage of T-bet⁺ cells in peripheral plasma cells of AIH patients (23.54 ± 1.61) % was higher than that of healthy volunteers (6.59±0.59) % , and the difference was statistically significant (P < 0.01). The correlation analysis showed that the proportion of T-bet⁺ cells in peripheral plasma cells of AIH patients was positively correlated with the proportion of plasma cells to B cells (r = 0.224 7, P < 0.01), and the percentage of peripheral plasma cells to B cells was positively correlated with the level of serum IgG (r = 0.299 1, P < 0.01). Serum IgG level was correlated with the level of ALT, reflecting an indicator of liver damage (t = 2.65, P < 0.05). Conclusion The increase of T-bet expression in the peripheral plasma cells of AIH patients is associated with liver damage, which is a new mechanism of AIH pathogenesis and disease progression.

Objective Childhood asthma is closely related to MP infection.This study was to investigate the distribution of ORMDL3 and HLA-DQ gene SNP in children with MP-associated asthma and gene-gene interactions.Methods One hundred and ninety-four patients with MP infection were enrolled.Extraction of whole blood genomic DNA was carried out.The genotype was collected by Flnidigm Juno 96.96 Genotyping integrated fluid pathway system.The patients were divided into MP-asthma group and MP-non-asthma group.Gene-gene interaction was analyzed by generalized multifactor dimensionality reduction.Results MP-asthma group included 63 cases (32.5％),MP-non asthma group included 131 cases (67.5％).ORMDL3 gene rs4794820 had three genotypes of AG,GG,AA.,MP-asthma group GG genotype and G allele frequency was higher than that in MP-non-asthma group.The frequency of AA genotype was the lowest among the two groups,but in the MP-non-asthma group were higher than that in the MP-asthma group.The rs7216389 had three genotypes of TT、TC、CC,the frequency of TT genotype and T allele in MP-asthma group was significantly higher than that in MP-non-asthma group.The frequency of CC genotype was the lowest among the two groups,but CC genotype in MP-non-asthma group was significantly higher than that in MP-asthma group.The rs794820 GG genotype and rs7216389 TT genotype were found to be risk factors.ORMDL3、HLA-DQA1 and HLA-DQA2 have gene-gene interaction.Conclusion MP infection is an important external cause of asthma in children.The genotype of rs7794820 GG genotype and rs7216389 TT genotype are an important internal cause of asthma after childhood MP infection.ORMDL3 rs4794820,rs7216389 and HLA-DQA1 rs9272346,HLADQA2 rs7773955 have gene-gene interaction,synergistically enhance the risk of asthma associated with asthma in children with MP.

As the achivement of a major project during the 12th Five-year Plan Period in China,the technique of anti-HBc quantification has been approved for commercial use and holds promise for wide application in clinical practice.Chinese scholars have explored the clinical significance of anti-HBc in various aspects and found that it has great values in the assessment of natural course of chronic hepatitis B virus (HBV) infection and the baseline prediction of antiviral therapy.Studies have shown that anti-HBc is significantly positively correlated with alanine aminotransferase (ALT) and significantly associated with liver inflammation.In chronic HBV infection patients with a normal ALT level,anti-HBc can be used instead as an indicator,with great significance for the development of therapeutic strategy in such patients.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

Objective To discuss the polymorphisms of asthma susceptibility gene ORMDL3 in infantile wheezing,in order to provide a theoretical basis for early diagnosis of asthma.Methods One hundred and fifty wheezing infants were recruited and divided into 2 groups as asthma predictive index(API) positive group(n =80) and negative group (n =70).Taqman probe was applied to detect the genotypes of 2 single nucleotide polymorphisms (SNPs)in childhood asthma susceptibility gene ORMDL3,which were rs4794820 and rs7216389.The genotype distributions were analyzed and compared between 2 groups,and the correlations among genotype distribution and tidal breath pulmonary function,fractional exhaled nitric oxide (FeNO) concentration,percentage of eosinophils (EOS％),serum immune globulin E (total IgE) levels respectively were also analyzed,respectively.Results (1) The frequencies of rs4794820 AG and rs7216389 TC heterozygotes in the API positive group were the highest,which were significantly higher than those in the negative group(58.75％ vs.31.42％,56.25％ vs.32.86％ respectively,all P ＜0.01).The frequencies of GG and TT homozygotes in the API negative group were the highest,which were significantly higher than those in the positive group (58.57％ vs.30.00％,57.14％ vs.31.25％ respectively,all P ＜0.01).(2)The time to reach the peak expiratory flow in tidal breathing over the total expiratory time (TPTEF/TE) and the volume to reach the peak expiratory flow in tidal breathing over the total expiratory volume (VPEF/VE) of the infants in the API positive group were less than those in the API negative group(16.87 ±5.31 vs.20.12 ± 5.23,20.87 ± 5.92 vs.25.56 ± 6.77,respectively),and the FeNO concentration was higher than that in the API negative group [(22.44 ± 9.77) ppb vs.(13.23 ± 7.90)ppb],and the differences were significant (t =-3.776,-4.490,6.377,respectively;all P ＜ 0.01).(3) In the API positive group,the TPTEF/TE and VPEF/VE of the infants who expressed AG/TC genotype were lower than those who expressed GG/TT genotype (14.55 ± 4.83 vs.19.91 ± 4.17,18.85 ± 4.26 vs.25.20 ± 7.06,respectively,t =-4.727,-3.976,all P ＜ 0.01);while the FeNO concentrations,EOS％ and total IgE levels were higher than those who expressed GG/TT genotype [(25.02 ± 8.77) ppb vs.(18.39 ± 6.56) ppb,7.16 ± 2.62 vs.5.50 ± 1.34,(366 727 ±275 533) IU/L vs.(166 826 ± 62 865) IU/L,respectively] (t =3.484,3.409,4.589 respectively;all P ＜ 0.01).Conclusions Childhood asthma susceptibility gene ORMDL3 SNPs rs4794820 AG and rs7216389 TC heterozygotes are the risk factors for API positive infantile wheezing.The pulmonary function damage and airway inflammation of the infants who expressed AG/TC genotype are more serious than those who expressed GG/TT genotype,and more likely to develop persistent asthma.

Objective To analyze the characteristics of drug resistance to quinolones and erythromycin of clinical Campylobacter jejuni (C .jejuni) strains and to further investigate its molecular mechanisms .Methods A total of 193 clinical C .jejuni strains were isolated from feces of patients with diarrhea .Drug susceptibilities to ciprofloxacin (CIP ) , gentamycin (GEN ) , azithromycin (AZI ) , erythromycin (ERY) ,chloromycetin (CHL) ,doxycycline (DOX) and tetracycline (TET) were tested using standard agar dilution method . gyrA , gyrB and parC genes were amplified by polymerase chain reaction (RCR) and analyzed for molecular mechanisms of quinolones resistance ,and 23S rRNA , rplD and rplV genes for erythromycin resistance .Chi‐square test or Fisher′s exact two‐tailed tests were used to perform the statistical analysis .Results A total of 193 clinical C . jejuni strains were isolated during 1994—2010 ,among which 43 C .jejuni strains were isolated in 1994—1999 ,80 in 2000—2005 and 70 in 2006—2010 .The drug resistance rates for CIP increased significantly from 55 .8% in 1994—1999 to 95 .0% in 2000—2005 and 94 .3% in 2005—2010 (χ2=41 .94 ,P<0 .01) .The drug resistance rates for GEN were 0 in 1994—1999 ,11 .3% in 2000—2005 and 10 .0% in 2006—2010 ,but with no statistic difference (χ2=5 .078 , P=0 .08) .The drug resistance rates for AZI were 0 in 1994—1999 ,3 .8% in 2000—2005 and 4 .3% in 2006—2010 (χ2=1 .81 ,P=0 .40) .The drug resistance rates for ERY were 0 in 1994—1999 ,1 .3% in 2000—2005 and 4 .3% in 2006—2010 (χ2 = 2 .87 , P= 0 .24 ) . T he drug resistance rates for CHL were 2 .3% in 1994—1999 ,11 .3% in 2000—2005 and 20 .0% in 2006—2010 (χ2 =7 .82 ,P=0 .02) .The drug resistance rates for DOX were 60 .5% in 1994‐1999 ,86 .3% in 2000—2005 and 82 .9% in 2006—2010 (χ2 =12 .18 ,P<0 .01) .The drug resistance rates for TET were 74 .4%in 1994—1999 ,95 .0% in 2000—2005 and 94 .3% in 2006—2010 (χ2 = 15 .46 , P< 0 .01 ) .T he drug resistance rates for CIP‐DOX‐TET were 37 .2% in 1994—1999 ,83 .8% in 2000—2005 and 80 .0% in 2006—2010 (χ2 =33 .53 ,P<0 .01) .The drug resistance rates for CHL‐CIP‐DOX‐TET were 0 in 1994—1999 ,7 .5% in 2000—2005 and 20 .0% in 2006—2010 (χ2=12 .68 ,P<0 .01) .The drug resistance rates for GEN‐CIP‐DOX‐TET were 0 in 1994—1999 ,7 .5% in 2000—2005 and 8 .6% in 2006—2010 (χ2 =3 .74 ,P=0 .15) .All 163 CIP‐resistant C .jejuni strains had C257T mutation on gyrA gene .Mutations on gyrB gene were silent .ParC gene was absent in C .jejuni .Four ERY resistant C .jejuni strains had no mutation on rplD and rplV genes , but 3 of them had A2075G mutation on 23S rRNA gene . Conclusions The antimicrobial resistance rates for C .jejuni increase remarkably over the periods .C257T mutation on gyrA gene and A2075G mutation on 23S rRNA gene are main mechanisms for quinolones resistance and erythromycin resistance ,respectively .