ObjectiveTo investigate the efficacy of C-reactive protein （CRP） in predicting the progression to acute-on-chronic liver failure （ACLF） within 90 days after disease onset in patients with acute decompensation （AD） of cirrhosis， and to provide a reference for the early identification of high-risk populations in clinical practice. MethodsA retrospective study was conducted among 906 patients with liver cirrhosis who were hospitalized due to AD in Nanjing Second Hospital from January 1， 2015 to October 31， 2024， and demographic features， AD type， and laboratory markers were collected on admission. The primary endpoint was progression to ACLF within 90 days after admission， and according to the presence or absence of ACLF， the patients were divided into non-ACLF group with 676 patients and ACLF group with 230 patients. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The univariate and multivariate Cox proportional-hazards regression models were used to identify independent predictive factors for ACLF. The receiver operating characteristic （ROC） curve was used to assess the predictive performance of CRP and existing scoring systems （Model for End-Stage Liver Disease ［MELD］， Child-Turcotte-Pugh ［CTP］ score， and Chronic Liver Failure Consortium Acute Decompensation ［CLIF-C AD］ score）， and the restricted cubic spline analysis was used to investigate the nonlinear relationship between CRP and the risk of ACLF. Youden index was used to determine the optimal predictive cut-off value for CRP， and the Kaplan-Meier survival curve was plotted for risk stratification， while the log-rank test was used for survival analysis. ResultsAmong the 906 AD patients， the incidence rate of ACLF was 25.39% within 90 days. The incidence rate of ACLF within 90 days was 45.1% in the 264 patients with bacterial infection and 17.3% in the 642 patients without bacterial infection （χ²=74.791， P<0.001）. Among the 906 patients， 312 patients （34.44%） had acute-on-chronic pre-liver failure （pre-ACLF）， with a significantly higher proportion of patients who progressed to ACLF than those in the non-pre-ACLF group ［60.58% （189/312） vs 6.90% （41/594）， χ²=310.234， P<0.001］. Among the 230 patients with ACLF， there were 102 patients with stable ACLF （44.35%） and 128 patients with unstable ACLF （55.65%）， with a significant difference in CRP between the two groups of patients （U=5 234.500， P<0.001）. The restricted cubic spline analysis showed a significant nonlinear relationship between CRP and the risk of ACLF （P<0.001）. The optimal cut-off value of CRP was determined as 10.16 mg/L based on the Youden index， with a sensitivity of 70.4% and a specificity of 64.5%. The Kaplan-Meier curve analysis showed that the high-risk group with CRP≥10.16 mg/L had a significantly higher event-free survival rate of ACLF within 90 days compared with the low-risk group （P<0.001）. The multivariate Cox regression analysis showed that AD type-hepatic encephalopathy （hazard ratio ［HR］=4.199， 95% confidence interval ［CI］： 3.056 — 5.770， P<0.001）， AD type-bacterial infection （HR=1.826， 95%CI： 1.356 — 2.459， P<0.001）， CRP （≥10.16 mg/L） （HR=2.356， 95%CI： 1.825 — 3.047， P<0.001）， white blood cell count （HR=1.021， 95%CI： 1.002 — 1.041， P=0.035）， hemoglobin （HR=0.994， 95%CI： 0.989 — 0.999， P=0.025）， international normalized ratio （HR=1.657， 95%CI： 1.372 — 2.001， P<0.001）， total bilirubin （HR=1.003， 95%CI： 1.002 — 1.004， P<0.001）， albumin （HR=0.956， 95%CI： 0.926 — 0.986， P=0.004）， creatinine （HR=1.005， 95%CI： 1.004 — 1.006， P<0.001）， serum sodium （HR=0.976， 95%CI： 0.956 — 0.997， P=0.025）， and lactate dehydrogenase （HR=1.001， 95%CI： 1.001 — 1.002， P<0.001） were all independent predictive factors for progression to ACLF within 90 days. The ROC curve analysis showed that CRP alone had an area under the ROC curve （AUC） of 0.724 （95%CI： 0.685 — 0.763） in predicting ACLF， and CRP+MELD score had the best predictive performance （AUC=0.870， 95%CI： 0.843 — 0.898）， while CRP+CTP score and CRP+CLIF-C AD score had an AUC of 0.852 （95%CI： 0.823 — 0.881） and 0.845 （95%CI： 0.812 — 0.877）， respectively. There was a significant increase in model performance after integration （P<0.05）. ConclusionSerum CRP level on admission is an independent predictive factor for progression to ACLF within 90 days in patients with AD of cirrhosis， and a CRP level of ≥10.16 mg/L can be used as a simple threshold for identifying high-risk patients. Incorporating CRP into existing assessment systems may enhance the early identification of patients at a high risk for ACLF， which provides a reference for clinical intervention.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Objective To compare the effects of main artery clamping(MAC)and selective artery clamping(SAC)strategies on postoperative renal function in patients with chronic renal insufficiency undergoing robot-assisted partial nephrectomy.Methods A retrospective cohort study was conducted on 231 patients with preoperative chronic renal insufficiency[eGFR<90 mL/(min·1.73 m2)with renal injury markers or eGFR<60 mL/(min·1.73 m2)]who underwent robot-assisted partial nephrectomy in the Department of Urology of the First Affiliated Hospital of Army Medical University from February 2018 to February 2024.According to intraoperative renal artery clamping strategy,they were divided into a MAC group(n=129)and a SAC group(n=102).Preoperatively,individualized renal artery clamping strategies were developed using a machine learning-based multimodal holographic 3-D reconstruction technique.Serum creatinine(Scr)level was measured at 3 d and 3 months after surgery,and estimated glomerular filtration rate(eGFR)was calculated using the chronic kidney disease epidemiology collaboration equation(CKD-EPI)formula.Renal dynamic imaging with 99mTc-DTPA or 99mTc-MAG3 was used to assess the GFR of the affected kidney.Results At 3 d after surgery,the decrease in GFR of the affected kidney was significantly lower[(8.3±7.7)vs(16.0±10.2)mL/(min·1.73 m2),95%CI:-10.2～-5.2,P<0.001]in the SAC group than the MAC group.Scr increment analysis showed that the SAC group exhibited notably lower Scr increase[8.2(2.5,18.7)vs 15.5(5.8,28.3)μmol/L,95%CI:-12.3～-1.8,P=0.027],and milder eGFR decline[3.0(0.5,7.8)vs 7.5(2.0,14.3)mL/(min·1.73 m2),95%CI:-6.2～-0.8,P=0.015].And,in 3 months after surgery,the SAC group had lower Scr level[(89.2±23.1)vs(95.3±22.1)μmol/L,95%CI:-11.9～-0.3,P=0.042],and higher GFR of the affected kidney[(33.5±10.5)vs(26.1±10.9)mL/(min·1.73 m2),95%CI:4.6～10.2,P<0.001].Conclusion For patients with chronic renal insufficiency undergoing robot-assisted partial nephrectomy,SAC strategy is superior to MAC strategy in protecting postoperative renal function without increasing surgical risk.

A method was developed for determination of dilauryl thiodipropionate(DLTDP)in fried foods by coupling solid-phase extraction(SPE)pretreatment with reverse-phase liquid chromatography-tandem mass spectrometry(RPLC-MS/MS)detection.Samples were extracted with n-hexane as the solvent,purified using a neutral alumina SPE cartridge,and finally analyzed by RPLC-MS/MS.Quantitative analysis was performed using matrix-matched calibration curves combined with an external standard method under optimal experimental conditions.The results showed that DLTDP exhibited good linearity in the range of 2.0-50.0 μg/L,with a correlation coefficient(R2)≥0.999.The limit of detection(LOD)and the limit of quantification(LOQ)of the method were 0.15 mg/kg and 0.5 mg/kg,respectively.The mean recoveries at three fortification levels(0.5,1.0,and 200 mg/kg)in different samples ranged from 84.8%to 96.8%,with the relative standard deviations(RSDs)all less than 8.0%.The developed method was highly sensitive,accurate and reliable,and easy to operate,making it well suited for the routine quantitative analysis of DLTDP in fried foods.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Objective:To obtain a polyvalent single-chain variable fragment（scFv）against West Nile virus through PEGylation in order to improve its antigen-binding ability and neutralizing activity.Methods:A scFv carrying a C-terminal cysteine residue（scFvC）was constructed by introducing Cys into the C-terminal of scFv against West Nile virus. Then the multimerization of scFvC was achieved by targeting the thiol group of Cys with maleimide-activated polyethylene glycol. ELISA was used to detect the antigen-binding activity of the multivalent scFvC. Pseudovirus-based neutralization assay was used to evaluate the neutralizing activity of the multivalent scFvC in vitro. One-way analysis of variance was used for statistical analysis. Results:The PEGylated scFvC multimers showed higher antigen-binding ability than the monomeric scFvC. In the pseudovirus-based neutralization assay，both monomeric scFvC and PEGylated scFvC multimers showed good neutralizing activity compared with the control group（ P<0.000 1）. Moreover，the PEGylated scFvC multimers showed a more effective ability to block the pseudovirus infection in target cells（ P<0.05），suggesting that the PEGylated scFvC multimers could enhance their function in vitro through avidity effect. Conclusion:In this study，a scFvC targeting West Nile virus is successfully constructed and its polyvalent form is generated through PEGylation，which improves the antigen-binding and neutralizing activity of the parental scFv.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

OBJECTIVE: To explore the therapeutic effect of polygonum cuspidatum glycoside on steroid-induced osteonecrosis of the femoral head(SONFH) in rats and its potential mechanism of protecting bone tissue by regulating the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway(JAK2/STAT3). METHODS: Fifty male SD rats were randomly divided into control group, model group, low-dose polygonum cuspidatum glycoside group (polygonum cuspidatum glycoside-L), high-dose polygonum cuspidatum glycoside group (polygonum cuspidatum glycoside-H), and polygonum cuspidatum glycoside-H+Colivelin (JAK2/STAT3 pathway activator) group. SONFH model was induced by lipopolysaccharide and dexamethasone. The treatment groups were given polygonum cuspidatum glycoside orally(polygonum cuspidatum glycoside-L 10 mg·kg^-1, polygonum cuspidatum glycoside-H 20 mg·kg^-1, and the polygonum cuspidatum glycoside-H+Colivelin group was injected with Colivelin (1 mg·kg^-1) intraperitoneally once a day, while the control and model groups were given an equal volume of saline for 6 weeks. The observed indicators included serum calcium(Ca), serum phosphorus (P), alkaline phosphatase, and transforming growth factor β1(TGF-β1) levels, micro-CT scanning, hematoxylin-eosin staining, and Western blot detection of JAK2/STAT3 signaling pathway and osteogenic differentiation marker genes, including Runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (BMP2), and osteopontin (OPN) protein expression. RESULTS: Compared with the model group, the trabecular bone area percentage in the polygonum cuspidatum glycoside-L and polygonum cuspidatum glycoside-H groups was significantly increased, and the empty lacunar rate was significantly decreased (P<0.05). Micro-CT analysis showed that the bone volume fraction, trabecular number, and thickness increased, and the trabecular separation decreased in the polygonum cuspidatum glycoside-treated groups(P<0.05). Serum biochemical tests found that the serum Ca and P concentrations in the polygonum cuspidatum glycoside-L and polygonum cuspidatum glycoside-H groups were restored, the alkaline phosphatase levels decreased, and the transforming growth factor β1 levels increased (P<0.05). Western blot analysis showed that polygonum cuspidatum glycoside significantly inhibited the activation of the JAK2/STAT3 signaling pathway in the model group and promoted the expression of osteogenic differentiation marker genes such as Runx2, BMP2, and OPN (P<0.05). Compared with the polygonum cuspidatum glycoside-H group, the improvements in the polygonum cuspidatum glycoside-H+Colivelin group were somewhat weakened, indicating the importance of the JAK2/STAT3 signaling pathway in the action of polygonum cuspidatum glycoside. CONCLUSION polygonum cuspidatum glycoside promotes osteogenic differentiation, improves bone microstructure, and has significant therapeutic effects on rat SONFH by regulating the JAK2/STAT3 signaling pathway.
Animals ; Male ; Janus Kinase 2/physiology* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Glucosides/pharmacology* ; STAT3 Transcription Factor/genetics* ; Femur Head Necrosis/chemically induced* ; Stilbenes/pharmacology*