It is estimated that approximately seven million people worldwide are affected by inflammatory bowel disease(IBD),causing a huge burden on healthcare systems and society.In the occurrence,progression,and treatment of IBD,the intestinal microbiota and its key metabolic product,bile acids,play a crucial role.The intestinal microbiota not only participates in the biotransformation of bile acids,enriching the diversity of bile acids,but also regulates their synthesis and transport through the farnesoid X receptor(FXR).Meanwhile,bile acids contribute to regulating the structure and function of the intestinal microbiota by supporting microbial diversity,exerting direct toxicity,participating in indirect antimicrobial pathways,and influencing microbial metabolic capabilities.Furthermore,under normal physiological conditions,intestinal microbiota-derived bile acids facilitate the repair process of the intestinal epithelial barrier.They also promote the balance of the immune system by modulating the functions of various immune cells including helper T(Th)cells 17,regulatory T(Treg)cells,CD8+T cells and natural killer T(NKT)cells,thereby slowing down the development of IBD.This article focuses on exploring the role of intestinal microbiota and bile acids in the onset and progression of IBD,and investigating new effective treatment strategies by targeting intestinal microbiota and bile acids,such as bile acid receptor modulators,probiotics,prebiotics,fecal microbiota transplantation(FMT),and phage therapy.

With the increasingly wide application of herbal medicines and dietary supplements worldwide,herb-induced liver injury(HILI)has become an important etiology of drug-induced liver injury.Due to the diverse manifestations of HILI,the difficulty in medical history collection,and the lack of specific biomarkers,how to identify suspected patients and make a correct diagnosis has become a major challenge in practice.Causality assessment is commonly used in the diagnosis of HILI,but there is still a lack of prospective cohort studies with a large sample size.In addition,further studies are needed to search for the specific biomarkers for the diagnosis of HILI.The diagnosis and differential diagnosis of HILI are challenging,and currently there is still no universally accepted uniform and standard method for the diagnosis of all-cause HILI.

Cancer has become a major life-threatening disease globally.In recent years,precision therapy for cancer has gradually emerged,and significant success has been achieved with targeted therapies,immune checkpoint inhibitors,and the newly emerging antibody-drug conjugates(ADC).The development of ADC has been rapid,with up to 15 ADC drugs currently approved worldwide.However,the hepatotoxicity of ADC has gained increasing attention,with reports of fatal hepatotoxic events.In this article,we briefly reviewed the ADC approved globally,summarized the liver-related adverse events and hepatotoxic manifestations reported in current clinical trials of ADC,and compiled research on possible hepatotoxicity mechanisms.Our aim is to assist clinicians in understanding and managing the hepatotoxicity characteristics of ADC,enabling timely identification of patients at risk of hepatotoxicity and implementing effective measures to manage these risks,thus reducing and preventing serious adverse events.

Cancer has become a major life-threatening disease globally.In recent years,precision therapy for cancer has gradually emerged,and significant success has been achieved with targeted therapies,immune checkpoint inhibitors,and the newly emerging antibody-drug conjugates(ADC).The development of ADC has been rapid,with up to 15 ADC drugs currently approved worldwide.However,the hepatotoxicity of ADC has gained increasing attention,with reports of fatal hepatotoxic events.In this article,we briefly reviewed the ADC approved globally,summarized the liver-related adverse events and hepatotoxic manifestations reported in current clinical trials of ADC,and compiled research on possible hepatotoxicity mechanisms.Our aim is to assist clinicians in understanding and managing the hepatotoxicity characteristics of ADC,enabling timely identification of patients at risk of hepatotoxicity and implementing effective measures to manage these risks,thus reducing and preventing serious adverse events.

Excessive N-acetyl-p-benzoquinone imine(NAPQI)formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen(APAP)overdose caused acute liver failure(ALF).S-glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity.Glutaredoxin-1(Glrx1),a glutathione-specific thioltransferase,is a primary enzyme to catalyze deglutathionylation.The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP.The Glrx1 knockout mice(Glrx1-/-)and liver-specific overexpression of Glrx1(AAV8-Glrx1)mice were produced and underwent APAP-induced ALF.Pirfenidone(PFD),a potential inducer of Glrx1,was administrated preceding APAP to assess its protective effects.Our results revealed that the hepatic total protein S-glutathionylation(PSSG)increased and the Glrx1 level reduced in mice after APAP toxicity.Glrx1-/- mice were more sensitive to APAP overdose,with higher oxidative stress and more toxic metabolites of APAP.This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the S-glutathionylation of cytochrome p450 3a 11(Cyp3a11),which likely increased the activity of Cyp3a11.Conversely,AAV8-Glrx1 mice were defended against liver damage caused by APAP overdose by inhibiting the S-glutathionylation and activity of Cyp3a11,which reduced the toxic metabolites of APAP and oxidative stress.PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress.We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose.Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.

OBJECTIVE To study the mechanism of Suyu tongfeng prescription against gouty arthritis . METHODS Male SD rats were randomly divided into normal control group ，model group ，colchicine tablets group （positive control drug ，0.3 mg/kg） and high -dose，medium-dose and low -dose groups （5，2.5，1.25 g/kg）of Suyu tongfeng prescription according to body mass ，with 10 rats in each group . The rats in the administration group were orally given the corresponding drugs once a day （10 mL/kg）for 7 consecutive days . Rats in the normal control group and model group were given equal volume of water intragastrically . On the 6th day，1 h after administration ，except for normal control group ，the rats in other groups were injected with sodium urate into the joint to replicate the gouty arthritis model . The degree of joint swelling and the score of inflammatory indexes were measured at 2， 6 and 24 h after the establishment of the model . One hour after the last administration ，the activity of oxidative stress related indicators [superoxide dismutase （SOD），xanthine oxidase （XOD），malondialdehyde（MDA）] and the levels of inflammatory factors [interleukin 1β（IL-1β），IL-18，tumor necrosis factor α were detected in the serum . The histopathological changes of ankle joints in each group were observed ；the expressions level of thioredoxin interacting protein （TXNIP）， mail：150120239@qq.com NOD like receptor thermoprotein domain related protein 3 （NLRP3），apoptosis related spot like protein （ASC）in the @qq.com ankle joint of rats were detected . RESULTS After intervened with Suyu tongfeng prescription ，the swelling degree of joints ，the score of inflammation indexes ，the edema of synovial tissue and the amount of inflammatory cells were reduced . The activity of SOD in Suyu tongfeng prescription high -dose group was increased significantly（P＜0.01），while the activities of XOD and MDA as well as the levels of IL -1β，IL-18 and TNF -α were all decreased significantly（P＜0.01）. The level of ROS and the protein expressions of TXNIP ，NLRP3 and ASC in ankle joint were all decreased significantly （P＜0.05 or P＜0.01）. The activities/levels of the above indexes were also significantly reversed in the middle-dose and low -dose groups of Suyu tongfeng prescription （P＜0.05 or P＜0.01）. CONCLUSIONS Suyu tongfeng prescription can inhibit the activation of NLRP 3 inflammasome through ROS/TXNIP/NLRP 3 signaling pathway ，and then play the role of anti -gouty arthritis .

Objective:To analyze and compare the clinical characteristics and prognosis of imported patients infected with 2019 novel coronavirus (2019-nCoV) Omicron variants and Delta variants, so as to provide references for clinical diagnosis, treatment and epidemic prevention strategies.Methods:The patients with imported 2019-nCoV infection from August 1, 2021 to January 18, 2022 in Guangzhou Eighth People′s Hospital, Guangzhou Medical University were retrospectively analyzed. According to the whole genome sequencing of 2019-nCoV in nasal or throat swabs, they were divided into Omicron group and Delta group. The clinical characteristics, laboratory tests, antibody levels, viral nucleic acid (the cycle threshold (Ct) of N gene and open reading frame ( ORF) 1 ab), main treatment measures and clinical prognosis were analyzed in the two groups. Statistical analysis was performed using the rank sum test, chi-square test or Fisher′s exact test. Results:A total of 344 cases were enrolled, including 152 cases in the Delta group and 192 cases in the Omicron group, and there were 240 males (69.8%), with a median age of 33 years old. One hundred and two (29.7%) of those patients had underlying disease.Two hundred and seventy-one had completed full or booster vaccination. The overall full vaccination rate in Omicron group was 70.8%(136/192), which was higher than 51.3%(78/152) in Delta group. The proportion of mild patients in Omicron group was higher than that in Delta group (57.3%(110/192) vs 24.3%(37/152), respectively), and the proportions of common type and severe type were lower than those of the Delta group (33.9%(65/192) vs 55.3%(84/152) and 0(0/192) vs 10.5%(16/152)), the differences were all statistically significant ( χ2=37.64 and 15.84, respectively, Fisher′s exact test; all P<0.001). The duration and peak of fever in Omicron group were 1.5(1.0, 2.0) d and 38.1(37.8, 38.5) ℃, respectively, which were lower than those in Delta group (3.0(1.0, 4.8) d and 38.5(38.1, 39.0) ℃, respectively), and the differences were both statistically significant ( Z=-4.14 and -3.85, respectively, both P<0.001). The 2019-nCoV antibody IgG and the Ct values of virus nucleic acid N gene and ORF1 ab gene in the vaccinated Omicron group at admission were higher than those in the Delta group ( Z=-3.25, -2.18 and -2.82, respectively, all P<0.050). Compared with patients in Delta group, patients in Omicron group had lower proportion of receiving respiratory therapy support, shorter oxygen therapy time, shorter reversion time from admission to nucleic acid Ct value≥35 and shorter hospitalization time. The differences were all statistically significant ( χ2=47.86, Z=-5.41, -5.60 and -4.71, respectively, all P<0.001). There was no critical illness or 28-day death case in both groups. Conclusions:The severity of patients infected with Omicron variants is lighter than that of patients with Delta variants, and the viral nucleic acid has shorter conversion time, which is mainly related to the virulence of variant strain and vaccination.

Adenomyosis is a common disease in women of childbearing age, and is one of the important causes of infertility. Based on the relationship between adenomyosis and infertility, and the impact of adenomyosis on the outcome of assisted reproductive technology (ART), this article focused on the strategies of ART for patients with adenomyosis complicated with infertility, discussing the indications and timing of ART, pretreatment strategies, ovarian stimulation protocols and embryo transfer strategies.

Adenomyosis is a common disease in women of childbearing age, and is one of the important causes of infertility. Based on the relationship between adenomyosis and infertility, and the impact of adenomyosis on the outcome of assisted reproductive technology (ART), this article focused on the strategies of ART for patients with adenomyosis complicated with infertility, discussing the indications and timing of ART, pretreatment strategies, ovarian stimulation protocols and embryo transfer strategies.

Objective:To investigate the efficacy of early versus delayed laparoscopic cholecystectomy (LC) in the treatment of acute calculous cholecystitis complicated by abnormal liver function. Methods:A total of 106 patients with acute calculous cholecystitis complicated by abnormal liver function who received LC in Nanjing Drum Tower Hospital, Nanjing University Medical School, China between February 2018 and February 2020 were included in this study. They were assigned to receive laparoscopic cholecystectomy either within 72 hours after disease onset (early group, n = 51) or 72 hours after disease onset (delayed group, n = 51). Perioperative indexes, complications, immune function and liver function were compared between the two groups. Results:Intraoperative blood loss in the early group was less than that in the delayed group [(63.11 ± 8.18) mL vs. (92.39 ± 7.23) mL, t = 19.558, P < 0.001]. Operative time, time to anal exhaust and length of hospital stay in the early group were (49.53 ± 6.33) minutes, (23.24 ± 4.65) hours and (6.38 ± 1.23) days in the early group were significantly shorter than those in the delayed group [(63.24 ± 5.42) minutes, (32.88 ± 5.78) hours, (8.34 ± 1.54) days, t = 12.004, 9.415, 7.204, all P < 0.001]. There was no significant difference in the rate of conversion to open cholecystectomy during LC between the two groups ( χ2 = 0.877, P > 0.05). There was no significant difference in the incidence of complications between early and delayed groups [11.76% (6/51) vs. 7.27% (4/55), χ2 = 0.625, P > 0.05]. On day 3 after surgery, the proportion of CD 3+ cells and the ratio of CD 4+/CD 8+ cells in the early group were (37.81 ± 4.29) % and (1.32 ± 0.29), respectively, which were significantly higher than those in the delayed group [(32.56 ± 5.26) %, 1.21 ± 0.23, t = 5.605, 6.379, both P < 0.001]. Total bilirubin, alanine aminotransferase and alkaline phosphatase levels in the early group were (21.05 ± 5.16) μmol/L, (71.58 ± 9.36) U/L and (175.73 ± 19.64) U/L, respectively, which were significantly lower than those in the delayed group [(27.81 ± 5.14) μmol/L, (82.54 ± 12.35) U/L, (214.62 ± 20.58) U/L, t = 6.921, 7.893, 9.865, all P < 0.001]. On day 5 after surgery, total bilirubin, alanine aminotransferase and alkaline phosphatase levels in the early group were (14.63 ± 4.58) μmol/L, (42.13 ± 8.24) U/L, (137.72 ± 17.62) U/L, respectively, which were significantly lower than those in the delayed group [(18.67 ± 6.45) μmol/L, (59.64 ± 11.29) U/L, (162.76 ± 18.39) U/L, t = 3.692, 8.265, 7.462, all P < 0.001]. Conclusion:Early LC for treatment of acute calculous cholecystitis complicated by abnormal liver function can effectively promote the recovery of liver function, mitigate immune injury, improve perioperative indicators, and dose not increase the incidence of complications.