OBJECTIVE To assess the safety profile of sintilimab in combination with chemotherapy for the treatment of cholangiocarcinoma. METHODS The data of patients with cholangiocarcinoma from January 1st， 2021 to December 31st， 2022 were collected and divided into control group （29 cases） and observation group （18 cases） based on different medication regimens. Patients in the control group were treated with Gemcitabine hydrochloride for injection+Cisplatin for injection or Oxaliplatin for injection， the observation group was treated with Sintilimab injection based on the control group. Patients in each group underwent blood routine， liver and kidney function， biochemical and other examinations before and after each treatment cycle to observe the occurrence of adverse drug reactions. The correlation of adverse drug reactions with drugs was evaluated with Naranjo’s scale. RESULTS The correlation between blood toxicity and drug use was deemed “probable” in both groups； however， the observation group exhibited a significantly higher score， indicating a stronger correlation. In the control group， hepatotoxic reactions were classified as “suspicious” whereas in the observation group， they were categorized as “probable”. The correlation of gastrointestinal symptoms between the two groups was considered “possible”. Systemic symptoms， skin toxicity， musculoskeletal toxicity， endocrine toxicity and renal toxicity were all classified as having a “suspicious” correlation with drug use. The total incidence of blood toxicity in the observation group was significantly higher than control group （P＝0.014）. There was no statistically significant difference in the total incidences of hepatotoxic， gastrointestinal symptoms， systemic symptoms， skin toxicity， musculoskeletal toxicity， endocrine toxicity， renal toxicity， or the incidence of grade 3 or higher blood toxicity， hepatotoxic between the two groups （P＞0.05）. For the patients experiencing adverse drug reactions， the symptoms were alleviated following drug discontinuation or symptomatic supportive treatment. No fatalities occurred during the treatment period. CONCLUSIONS Sintilimab combined with chemotherapy may significantly increase the risk of blood toxicity in patients with cholangiocarcinoma， especially thrombocytopenia， but the adverse reactions are within a controllable range， and the overall safety is good.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Introduction::The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored.Methods::We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People’s Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects.Results::At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively ( P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence ( P for nonlinear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880). Conclusion::Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

Objective:To investigate the impact of geniposide(GE)on lung injury in rats with acute respiratory distress syn-drome(ARDS)by regulating AMP-activated protein kinase(AMPK)/silencing information regulator 1(SIRT1)/nuclear factor κB(NF-κB)signaling pathway.Methods:The ARDS rat model was established by tracheal instillation of lipopolysaccharide(LPS).Fifty rats after modeling were randomly group into ARDS group,GE low-dose(GE-L,12.5 mg/kg GE)group,GE medium-dose(GE-M,25 mg/kg GE)group,GE high-dose group(GE-H,50 mg/kg GE)group and GE-H+Compound C(AMPK inhibitor,50 mg/kg GE+250 μg/kg Compound C)group,another 10 normal rats were used as the control group.After the intervention,the bronchoalveolar la-vage fluid(BALF)and lung tissue of the rats in each group were taken out,respectively,and the ratio of lung wet to dry weight(W/D)was detected;ELISA was used to detect the levels of inflammatory factors IL-6,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α)in BALF;the positive expressions of vascular cell adhesion factor(VCAM-1)and vascular endothelial cell growth factor(VEGF)in lung tissue were detected by immunohistochemistry;HE staining was used to observe the pathological changes of lung tissue;Western blot was used to detect the expression levels of AMPK/SIRT1/NF-κB pathway proteins in lung tissue.Results:The levels of W/D,IFN-γ,IL-6,TNF-α,p-NF-κB p65/NF-κB p65 and VCAM-1 in ARDS group were significantly higher than those in control group,the expressions of p-AMPK/AMPK,SIRT1 and VEGF were significantly decreased(P<0.05);after different doses of GE treatment,the levels of W/D,IFN-γ,IL-6,TNF-α,and the expressions of p-NF-κB p65/NF-κB p65 and VCAM-1 were gradually decreased compared with those in ARDS group;the expressions of p-AMPK/AMPK,SIRT1 and VEGF increased gradually(P<0.05);Compound C reversed the protective effect of GE-H on ARDS rats(P<0.05).Conclusion:GE can improve lung injury in ARDS rats and reduce levels of inflammatory factors,which may be related to activation of AMPK/SIRT1/NF-κB signaling pathway.

Objective To explore the hearing and cochlear histomorphological changes in APP/PS1 transgenic mice during the process of AD and to determine whether the occurrence and development of AD affect their hearing function.Methods APP/PS1 transgenic mice and wild type littermates were selected at the ages of4,8 and 12 months.Changes to the auditory function of APP/PS1 transgenic mice over time were detected by immunofluorescence staining and auditory brainstem response(ABR)test.Results Compared with the control group,the 4-month-old APP/PS1 transgenic mice had a significantly increased number of Aβ plaques in the hippocampus,indicating that AD symptoms were already present at this time.At the ages of 4,8 and 12 months,there was no significant difference in the hearing threshold between APP/PS1 transgenic mice and wild type mice.Histomorphological examination of the cochlea showed no significant difference in key cells of he inner ear,such as cochlear hair cells and spiral ganglion,between the two groups of mice.An ABR test showed that the hearing threshold of both APP/PS1 transgenic mice and wild type littermates increased significantly with age,and both groups showed age-related hearing loss.Conclusions There was age-related hearing loss in APP/PS1 transgenic mice,but the occurrence and development of AD had little effect on their auditory functions.

Objective To investigate correlation between serum bilirubin levels of different subtypes and diabetic nephropathy(DN)in patients with type 2 diabetes mellitus(T2DM).Methods Clinical data of 494 patients with T2DM admitted to Suizhou Central Hospital Affiliated to Hubei Medical University from January 2019 to May 2023 were retrospectively analyzed,and they were divided into DN group(175 cases)and non-DN group(319 cases)according to whether they had DN.Correlation between levels of total bilirubin(TBil),direct bilirubin(DBil),indirect bilirubin(IBil)in serum and the occurrence of DN were analyzed.Results There were statistically significant differences on age,course of diabetes,hypertension,coronary heart disease,smoking,drinking,TBil,DBil,IBil,alanine aminotransferase(ALT),blood urea nitrogen(BUN),serum creatinine(SCr),uric acid(UA),total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL),high density lipoprotein(HDL),glycosylated hemoglobin(HbA1c),body mass index(BMI),systolic blood pressure,fasting plasma glucose(FPG)and estimated glomerular filtration rate between two groups.Age,course of diabetes,hypertension,coronary heart disease,TBil,DBil,IBil,ALT,BUN,SCr,UA,TC,TG,HDL,LDL,HbA1c,BMI and FPG were influencing factors of DN in female T2DM patients(P<0.05).Age,course of diabetes,hypertension,coronary heart disease,smoking,alcohol consumption,TBil,DBil,IBil,ALT,BUN,SCr,UA,TC,TG,HDL,LDL,HbA1c,BMI and FPG were influencing factors of DN in male T2DM patients(P<0.05).TBil,DBil and IBil were significantly correlated with development of DN in patients with T2DM(P<0.001).Risk of developing DN gradually decreased with increasied TBil(1-15 μmol/L),IBil(1-10 μmol/L)and DBil(1-4 μmol/L),but after TBil>15 μmol/L,IBil>10 μmol/L and DBil>4 μmol/L,increased in TBil,DBil and IBil levels no longer reduced risk of developing DN.Conclusion There is a non-linear correlation between levels of TBil,DBil,IBil and risk of DN in patients with T2DM.Within a certain range,TBil,DBil and IBil are independent protective factors for occurrence of DN,and reaching a certain level will no longer reduce risk of DN.There is no significant difference between serum bilirubin and risk of DN in different genders.

Objective:To study the correlation between zinc finger protein A20 (A20) and basic fibroblast growth factor (BFGF) and liver fibrosis in chronic hepatitis B.Methods:A retrospective study was conducted to select 120 patients with chronic hepatitis B diagnosed and treated in the Fifth Hospital of Shijiazhuang City from January 2019 to December 2020, all of whom underwent liver tissue biopsy, and 25 cases of liver pathological specimens who underwent liver hemangioma resection were selected. The correlation between the expression of A20 and BFGF in liver tissue and the stage of hepatic fibrosis and inflammation were analyzed.Results:The expression of A20 in the S1 - S4 phase was higher than that in the S0 phase: (6.12 ± 1.22)%, (10.18 ± 2.43)%, (16.94 ± 5.06)%, (25.99 ± 7.57)% vs. (0.81 ± 0.29)%; the expression of BFGF in the S1 - S4 phase was higher than that in the S0 phase: (6.12 ± 1.22)%, (10.18 ± 2.43)%, (16.94 ± 5.06)%, (25.99 ± 7.57)% vs. (0.81 ± 0.29)%, there were statistical differences ( P<0.05). The expression of A20 in the G1 - G4 phase was higher than that in the G0 phase: (6.56 ± 1.87)%, (10.01 ± 3.29)%, (15.54 ± 5.01)%, (25.86 ± 8.02)% vs. (0.85 ± 0.71)%; the expression of BFGF in the G1 - G4 phase was higher than that in the G0 phase: (5.91 ± 1.52)%, (9.65 ± 2.48)%, (15.03 ± 4.86)%, (24.62 ± 7.22)% vs. (0.79 ± 0.41)%, there were statistical differences ( P<0.05). The results of Pearson test showed that there was a positive correlation between liver A20 and BFGF ( r = 0.824, P<0.05). Conclusions:The expressions of A20 and BFGF in liver tissue increase with the aggravation of liver pathological fibrosis and inflammation, which can be used as important indicators to evaluate the severity of liver fibrosis.

Hearing loss is one of the most common neurosensory disorders in humans,severely affecting pa-tients'quality of life with lack of ideal treatments.Its pathogenesis is related to oxidative stress,inflammation and apoptosis in the inner ear.Recent studies have demonstrated that members of the signal transducer and activator of transcriptions(STATs)family are involved in regulating gene expression in auditory cells during inner ear develop-ment and physiological activities such as apoptosis,oxidative stress,inflammation and autophagy during auditory disorders.In this paper,we review the research on STATs in inner ear development and hearing loss,and elucidate their specific molecular mechanisms,aiming to provide theoretical guidance and direction for the prevention and treatment of hearing loss.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To study the ultrasonographic manifestations of intercostal muscle and diaphragm involvement in Duchenne muscular dystrophy (DMD) and their correlations with functional status, and to explore the pattern of muscle damage in patients with DMD and the potential role of ultrasonography in assessing disease progression.Methods:A total of 28 patients with DMD who received treatment in the Third Medical Centre of PLA General Hospital from May to December 2023 were prospectively collected as DMD group, and 28 healthy children matched in age and sex were included as controls for a prospective study.Diaphragm thickening fraction (DTF) and intercostal muscle thickening fraction (ICMTF) were measured by B-mode and M-mode ultrasonography, and the muscle gray values were recorded. The differences between groups were compared, and the values of DTF and ICMTF in evaluating the structural and functional changes of respiratory muscle were analyzed.Results:Compared with the control group, the gray value of respiratory muscle was significantly decreased in DMD group, the diaphragm and intercostal muscle were significantly thickened at the end of inspiratory and expiratory periods, DTF was significantly decreased, and ICMTF was significantly increased (all P<0.001). Conclusions:Ultrasound can evaluate the structural changes of respiratory muscle in DMD, so as to clarify the relationship between the structure and function of respiratory muscle in DMD patients.