ObjectiveTo analyze the expression level of triggering receptor expressed on myeloid cells-1 （TREM-1） in serum and ascites of patients with cirrhotic ascites， and to investigate its correlation with clinical features and inflammatory markers and its role in the diagnosis of infection and prognostic evaluation. MethodsA total of 110 patients with cirrhotic ascites who were hospitalized in The Fifth Hospital of Shijiazhuang from January 2019 to December 2020 were enrolled， and according to the presence or absence of intra-abdominal infection， they were divided into infection group with 72 patients and non-infection group with 38 patients. The patients with infection were further divided into improvement group with 38 patients and non-improvement group with 34 patients. Clinical data and laboratory markers were collected from all patients. Serum and ascites samples were collected， and ELISA was used to measure the level of TREM-1. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate the correlation between indicators. A multivariate Logistic regression analysis was used to identify the influencing factors for the prognosis of patients with cirrhotic ascites and infection. The receiver operating characteristic （ROC） curve was used to evaluate the diagnostic and prognostic efficacy of each indicator， and the Delong test was used for comparison of the area under the ROC curve （AUC）. ResultsThe level of TREM-1 in ascites was significantly positively correlated with that in serum （r=0.50， P<0.001）. Compared with the improvement group， the non-improvement group had a significantly higher level of TREM-1 in ascites （Z=-2.391， P=0.017） and serum （Z=-2.544， P=0.011）， and compared with the non-infection group， the infection group had a significantly higher level of TREM-1 in ascites （Z=-3.420， P<0.001）， while there was no significant difference in the level of TREM-1 in serum between the two groups （P>0.05）. The level of TREM-1 in serum and ascites were significantly positively correlated with C-reactive protein （CRP）， procalcitonin （PCT）， white blood cell count， and neutrophil-lymphocyte ratio （r=0.288， 0.344， 0.530， 0.510， 0.534， 0.454， 0.330， and 0.404， all P<0.05）. The ROC curve analysis showed that when PCT， CRP， and serum or ascitic TREM-1 were used in combination for the diagnosis of cirrhotic ascites with infection， the AUCs were 0.715 and 0.740， respectively. The multivariate Logistic regression analysis showed that CRP （odds ratio ［OR］=1.019， 95% confidence interval ［CI］： 1.001‍ ‍—‍ ‍1.038， P=0.043） and serum TREM-1 （OR=1.002， 95%CI： 1.000‍ ‍—‍ ‍1.003， P=0.016） were independent risk factors for the prognosis of patients with cirrhotic ascites and infection， and the combination of these two indicators had an AUC of 0.728 in predicting poor prognosis. ConclusionThe level of TREM-1 is closely associated with the severity of infection and prognosis in patients with cirrhotic ascites， and combined measurement of TREM-1 and CRP/PCT can improve the diagnostic accuracy of infection and provide support for prognostic evaluation.

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

AIM To investigate the consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma.METHODS Eighteen batches of standard decoctions were prepared,after which the extraction rate and contents,transfer rates of magnolflorine,jatrorrhizine,columbamine,epiberberine,coptisine,palmatine,berberin were determined,HPLC characteristic chromatograms were established.RESULTS There were 11 common peaks in the characteristic chromatograms of 18 batches of standard decoctions and 24 batches of formula granules with the similarities of 0.861-1.000,which were clusterd into two categories.The formula granules and standard decoction demonstrated approximated extraction rate and contents,transfer rates of index constituents.CONCLUSION The chemical constituents between formula granules and standard decoction of Coptidis Rhizoma display good consistency,which can provide references for the quality control,process research and clinical application of the former.

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 analyze the clinical and epidemiological characteristics of adult carotid body tumors (CBTs) in Northwest China to provide references for early diagnosis and treatment of CBTs.Methods:A multicenter, retrospective, non-intervention epidemiological investigation was conducted on adult CBTs patients who were hospitalized from January 1, 2011 to June 30, 2023 in 7 Class A tertiary hospitals in Northwest China (Departments of Neurosurgery, First Affiliated Hospital of Air Force Medical University, Second Affiliated Hospital of Lanzhou University, People's Hospital of Gansu Province, 940 th Hospital of PLA Joint Logistic Support Force, People's Hospital of Qinghai Province, General Hospital of Ningxia Medical University, People's Hospital of Ningxia Hui Autonomous Region). Medical records were collected in these patients, and they were divided into 2 groups according to their average altitude residence: high altitude group (≥1 500 m) and low altitude group (<1 500 m); meanwhile, these patients were divided into Shamblin type I, type II and type III groups according to Shamblin classification criteria; differences in general data and clinical features among patients from different altitude groups or Shamblin subgroups were compared. Independent influencing factors for Shamblin type III CBTs were analyzed by multivariate ordered Logistic regression. Results:(1) A total of 359 patients were enrolled in the study, including 276 females and 83 males, aged (48.80±12.07) years; 211 patients were into the high altitude group and 148 into the low altitude group; 165 patients were into Shamblin type I group, 146 into Shamblin type II group, and 48 into Shamblin type III group. (2) Compared with those in the low altitude group, patients in the high altitude group had higher proportion of females, older age, lower proportion of Han nationality, higher proportion of Shamblin type I, smaller tumor volume, lower platelet count, higher red blood cell count, hematocrit, hemoglobin level, platelet distribution width and mean platelet volume, and higher large platelet percentage, with significant differences ( P<0.05). (3) Compared with those in the Shamblin type I group, patients in the Shamblin type III group had younger age, lower resident altitude, larger tumor volume, longer time interval from onset to diagnosis, higher proportion of unintentional tumor discovery, larger volume of intraoperative blood loss, lower hemoglobin level, hematocrit, mean erythrocyte volume, and mean hemoglobin concentration, decreased erythrocyte distribution width variable coefficient, and increased platelet count, with significant differences ( P<0.05). Compared with those in the Shamblin type II group, patients in Shamblin type III group had younger age, larger tumor volume, longer time interval from onset to diagnosis, larger volume of intraoperative blood loss, lower hemoglobin, hematocrit and mean erythrocyte volume, higher erythrocyte distribution width variable coefficient and platelet count, with significant differences ( P<0.05). (4) Age ( OR=0.960, 95% CI: 0.942-0.977, P<0.001), residence altitude ( OR=0.992, 95% CI: 0.990-0.999, P=0.020) and time interval from onset to diagnosis ( OR=1.009, 95% CI: 1.005-1.014, P<0.001) were independent influencing factors for Shamblin type III CBTs. Conclusions:More females than males are noted in patients with adult CBTs in Northwest China, and more CBTs patients live at high altitude, with Shamblin type I enjoying the highest proportion. More female and old patients lived at high altitude is noted than those lived at low altitude; patients with Shamblin type III have the youngest age, lowest altitude, and longest time interval from onset to diagnosis. CBTs patients with young age, low residence altitude, and long time interval from onset to diagnosis are more likely to develop Shamblin type III.

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.
Mice ; Animals ; Hypoxia ; Oxidative Stress ; Autophagy ; Cognition ; Sirolimus/therapeutic use*

Objective:This study aims to evaluate the quality and explore the preliminary clinical applications of a domestically developed hepatitis D virus nucleic acid quantification reagent (abbreviated as"domestic HDV RNA reagent").Methods:The sensitivity and accuracy of the reagent were evaluated in accordance with the WHO HDV RNA international standard, employing the Bio-Rad CFX Opus 96 real-time fluorescence quantitative PCR analysis system. Serial dilutions of pseudo-viruses or cell culture-derived virus were used to determine the linear range of the domestic HDV RNA reagent. Specificity was assessed using positive samples of HAV, HBV, HCV infection, and HEV national reference materials. Precision was evaluated with samples at both high and low concentrations. In a comparative analysis, 30 HDV IgG positive samples were tested using both the domestic HDV RNA reagent and the RoboGene HDV RNA kit based on the ABI 7500 FAST DX system. The Pearson correlation coefficient (r) was used to examine the correlation between the two reagents.Results:The domestic HDV RNA reagent demonstrated a high sensitivity of up to 6 IU/ml, consistent with that of the comparator reagent. The calibration curve for WHO HDV RNA standards had a slope of -3.286, with an amplification efficiency of 101.6%. The linear detection range spanned from 10 to 10 8 IU/ml for eight HDV genotypes. The domestic HDV RNA reagent exhibited exceptional specificity, without cross-reactivity observed with HAV, HBV, HCV, or HEV. Accuracy assessments at five concentration levels met the required standards, with intra-assay precision coefficient of variation ( CV) ranging from 1.20% to 4.20%, and inter-assay precision CV from 1.20% to 7.90%. The detection results for HDV IgG positive samples were highly correlated with the comparator reagent ( r=0.984, P<0.001), achieving a diagnostic accuracy of 100% compared to sequencing results. Conclusion:In this study, the domestic HDV RNA reagent possesses excellent specificity, accuracy, precision, and a broad linear range, attaining a sensitivity level on par with international reagents of the same type.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Background/Aims: Steatotic liver disease (SLD) is a common manifestation in chronic hepatitis C (CHC). Metabolic alterations in CHC are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to elucidate whether hepatitis C virus (HCV) eradication mitigates MASLD occurrence or resolution. Methods: We enrolled 5,840 CHC patients whose HCV was eradicated by direct-acting antivirals in a nationwide HCV registry. MASLD and the associated cardiometabolic risk factors (CMRFs) were evaluated at baseline and 6 months after HCV cure. Results: There were 2,147 (36.8%) patients with SLD, and 1,986 (34.0%) of them met the MASLD criteria before treatment. After treatment, HbA1c (6.0% vs. 5.9%, p<0.001) and BMI (24.8 kg/m2 vs. 24.7 kg/m2, p<0.001) decreased, whereas HDL-C (49.1 mg/dL vs. 51.9 mg/dL, p<0.001) and triglycerides (102.8 mg/dL vs. 111.9 mg/dL, p<0.001) increased significantly. The proportion of patients with SLD was 37.5% after HCV eradication, which did not change significantly compared with the pretreatment status. The percentage of the patients who had post-treatment MASLD was 34.8%, which did not differ significantly from the pretreatment status (p=0.17). Body mass index (BMI) (odds ratio [OR] 0.89; 95% confidence intervals [CI] 0.85–0.92; p<0.001) was the only factor associated with MASLD resolution. In contrast, unfavorable CMRFs, including BMI (OR 1.10; 95% CI 1.06–1.14; p<0.001) and HbA1c (OR 1.19; 95% CI 1.04–1.35; p=0.01), were independently associated with MASLD development after HCV cure. Conclusions HCV eradication mitigates MASLD in CHC patients. CMRF surveillance is mandatory for CHC patients with metabolic alterations, which are altered after HCV eradication and predict the evolution of MASLD.