1.Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
Suqin YANG ; Sunbin LING ; Jianhua LI ; Yan WANG ; Jiapei WANG ; Qiwei HUANG ; Fanming LIU ; Yiqi ZHUANG ; Yingyu ZHENG ; Rui WANG ; Zhe YANG ; Xiaoping ZHENG ; Kai WANG ; Zhikun LIU ; Jun CHEN ; Jianguo WANG ; Haiyang XIE ; Lin ZHOU ; Leiming CHEN ; Guoqiang CAO ; Dandan CHEN ; Junfang JI ; Bin ZHAO ; Chao JIANG ; Di LU ; Xuyong WEI ; Hangjin JIANG ; Qiaonan SHAN ; Hengbo SHI ; Yong-Zhen XU ; Shusen ZHENG ; Zhengxin WANG ; Shengda LIN ; Xiao XU
Clinical and Molecular Hepatology 2026;32(2):884-903
Background/Aims:
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
2.Influence of CYP2C19 gene polymorphism on platelet function and inflammatory cytokines and analysis of factors associated with poor prognosis in elderly patients with ischemic stroke
Hai LIANG ; Hong ZHANG ; Runan XIA ; Huijuan CHEN ; Mengyu JIANG ; Fanqin LI ; Panpan DI ; Miao YANG
China Pharmacy 2026;37(6):782-787
OBJECTIVE To investigate the influence of CYP2C19 gene polymorphism on platelet function and inflammatory cytokines in elderly patients with ischemic stroke, and to analyze potential factors associated with poor prognosis. METHODS A retrospective study was conducted on elderly patients with ischemic stroke admitted to our hospital from June 2024 to June 2025, wh o underwent CYP2C19 genotype testing and received antiplatelet therapy with clopidogrel. The levels of platelet function indicators and inflammatory cytokines before and after treatment were compared among patients with different metabolic phenotypes. Based on the prognosis at 6 months post-treatment, patients were divided into poor prognosis group and good prognosis group. Univariate analysis was performed on general data, metabolic phenotype, the levels of platelet function indicators and inflammatory cytokines. Variables with P <0.05 and the levels of inflammatory cytokines before treatment were included in a multivariate Logistic regression analysis to identify independent risk factors for poor prognosis. Multiple linear regression was used to further analyze the relationship between metabolic phenotypes and inflammatory cytokines. RESULTS A total of 448 elderly patients with ischemic stroke were included; among them, 162 cases were normal metabolic phenotype, 218 were intermediate metabolic phenotype, and 68 were poor metabolic phenotype. No rapid or ultrarapid metabolic phenotypes were observed. After treatment, platelet aggregation rate, the levels of P-selectin and platelet activated complex-1 (PAC-1), high-sensitivity C-reactive Protein (hs-CRP), interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in the normal metabolic phenotype group, intermediate metabolic phenotype group, and poor metabolic phenotype group (except for platelet aggregation rate, and the levels of P-selectin and PAC-1 in the poor metabolic phenotype group) were significantly lower than those before treatment in the same group. Moreover, the above indicators in the normal metabolic phenotype group were significantly lower than those in the intermediate and poor metabolic phenotype groups at the corresponding time, and the levels of platelet function indicators in the intermediate metabolic phenotype group were significantly lower than those in the poor metabol ic phenotype group at the corresponding time ( P <0.05). Univariate and multivariate Logistic regression analyses showed that combined with hypertension, combined with diabetes mellitus, and intermediate or poor metabolic genotypes were independent risk factors for poor prognosis in elderly patients with ischemic stroke ( P <0.05). Multiple linear regression analysis showed that serum levels of hs-CRP, IL-1β, IL-6 and TNF-α before treatment were significantly higher in patients with intermediate and poor metabolic genotypes compared to those with normal metabolic genotype ( P <0.05), with a greater magnitude of increase in inflammatory cytokines observed in the patients with poor metabolic genotype. CONCLUSIONS The elderly ischemic stroke patients with CYP2C19 intermediate and poor metabolic genotypes have poor inhibition effect on platelet and higher levels of inflammatory cytokines than normal metabolic genotype; CYP2C19 gene polymorphism, and in combination with hypertension and diabetes, can be used as independent predictors of poor prognosis.
3.Association of sex hormone levels with all-cause mortality in males: a study based on NHANES
Jiahao WANG ; Shan JIANG ; Yilin ZHAO ; Haolin LI ; He ZHANG ; Di ZHU ; Jinzhi WANG ; Junqi WANG ; Peng GE
Journal of Modern Urology 2026;31(1):33-41
Objective To investigate the association of serum total testosterone(TT),free testosterone(FT),sex hormone-binding globulin(SHBG),and estradiol(E_2)with all-cause mortality rate(AMR)in males and to evaluate their predictive value. Methods Based on data from the National Health and Nutrition Examination Survey(NHANES)cycles(1999—2004 and 2013—2016),the relationships between different sex hormones and AMR was analyzed with Cox proportional hazards regression models. The dose-response relationships between different sex hormones and male AMR were assessed with restricted cubic splines(RCS). The predictive performances of different sex hormones for male AMR were compared with receiver operating characteristic(ROC)curves and the area under the curve(AUC). The survival differences across varying sex hormone levels were evaluated with Kaplan-Meier survival curves and log-rank tests. Results This study involved 3632 adult male participants with a median follow-up of 6.5 years,during which 320 AMR occurred(8.8%). Cox univariate analysis indicated that TT,FT and SHBG were risk factors for AMR(P<0.001). Cox multivariate analysis revealed that FT and SHBG were independent risk factors for AMR(FT:HR=0.90,95%CI:0.86-0.94; SHBG:HR=1.01,95%CI:1.01-1.02). RCS revealed a U-shaped nonlinear relationship between TT,FT and AMR(P<0.001); SHBG showed a positive dose-response relationship with AMR(P<0.001). The AUCs of FT predicting the 5-year,10-year,and 15-year AMR were 0.78(95%CI:0.73-0.82),0.80(95%CI:0.76-0.84),and 0.84(95%CI: 0.80-0.88),respectively,significantly outperforming other indicators. Subgroup analysis revealed that FT was negatively correlated with male AMR,but this association was modulated by age,race,smoking status and diabetes status(P_(interaction)<0.05). Kaplan-Meier survival analysis showed that different levels of TT and FT(Q1-Q4)were significantly positively correlated with survival rate(P<0.001),while different levels of SHBG were significantly negatively correlated with survival rate,with patients in the Q4 group having the highest risk of death(P<0.001). Conclusion Based on US NHANES,studies have shown that the FT and SHBG are independent risk factors for male AMR,and FT demonstrates greater predictive value for male AMR than TT.
4.Rationality and economic evaluation of Compound amino acid injection (14AA-SF) in the perioperative period of neurosurgery
Hai LIANG ; Jingjing WANG ; Huijuan CHEN ; Runan XIA ; Panpan DI ; Mengyu JIANG ; Fanqin LI ; Jinghe MA
China Pharmacy 2026;37(17):2303-2309
OBJECTIVE To establish standards for the rational use of Compound amino acid injection (14AA-SF) (hereinafter referred to as “14AA-SF”), and evaluate its rationality and cost-effectiveness.METHODS The standards for the rational use of 14AA-SF were established based on the Delphi method. Archived medical records of patients who used 14AA-SF in the Dept. of Neurosurgery of People’s Hospital of Bozhou from January 2024 to December 2025 were randomly selected. On the basis of the established standards for the rational use, the attribute hierarchical model was applied to evaluate the use rationality of 14AA-SF in the included medical records. The decision tree model was applied to calculate the incremental cost-effectiveness ratio (ICER), so as to evaluate the cost-effectiveness of 14AA-SF administered via single-bottle infusion versus “all-in-one” infusion, and the robustness of the cost-effectiveness evaluation results was verified through sensitivity analysis.RESULTS A total of 205 medical records were collected, among which 163 records (79.51%) were qualified with medical record score (MRS) ≥90, and 42 records (20.49%) were unqualified with MRS <90. The main irrational types of 14AA-SF use included unreasonable infusion method (67 case-times, accounting for 32.68%), unreasonable amino acid dosage (62 case-times, accounting for 30.24%) and unreasonable non-protein calorie-nitrogen ratio (55 case-times, accounting for 26.83%). Compared wtih single-bottle infusion, the incremental cost of “all-in-one” infusion for each 1% increase in effective rate was 165.40 yuan. The one-way sensitivity analysis showed that the effective rate of single-bottle infusion had the greatest impact on ICER. The probabilistic sensitivity analysis showed that under the willingness-to-pay (WTP) threshold (89 358 yuan) set in this study, the cost-effectiveness probability of “all-in-one” infusion relative to single-bottle infusion was 89.9%. When the WTP threshold exceeds 17 871.60 yuan, the “all-in-one” infusion is more cost-effective than the single-bottle infusion.CONCLUSIONS The established standards for the rational use of 14AA-SF are practical and feasible. There are phenomena of irrational use of 14AA-SF in Dept. of Neurosurgery of the hospital in terms of indications, nutritional risk screening, infusion methods and other aspects, which need to be further standardized. The “all-in-one” infusion is more cost-effective than the single-bottle infusion.
5.Current status of implementation of infection control core elements in grass-roots medical institutions under background of construction of"compact county-level medical communities"
Fangfang WANG ; Yuncui GUO ; Xiaoyan WU ; Haibo ZHANG ; Jing ZHOU ; Xu LIU ; Jia DI ; Shufang JIANG ; Chengyi FENG ; Xuemei LI
Chinese Journal of Nosocomiology 2025;35(18):2821-2825
OBJECTIVE To explore the implementation and standardized management of infection control core ele-ments in grass-roots medical institutions within county-level medical communities.METHODS From Mar.2024 to Apr.2024,the current status of implementation of infection control core elements in the grass-roots medical institu-tions within county-level medical communities was investigated by means of questionnaire survey and qualita-tive interview,and the implementation strategies were further explored.RESULTS The infection management or-ganizational system and functions of the two county-level medical institutions within the county medical communi-ties were completed,there is no independent hospital infection management department in the primary medical in-stitutions.The infection management personnel in the 16 grass-roots medical institutions were part-time person-nel,the personnel with the educational background below junior college accounted for 84.21%,the personnel with the professional background of nursing accounted for 100.00%,the personnel with less than 5 years of working experience accounted for 78.95%,none of them had an on-the-job training certificate.The monitoring programs of the county-level medical institutions within the county medical communities were completed,there was no infec-tion management monitoring information platform in the grass-roots medical institutions.The infection cases,hand hygiene,environmental health and occupational exposures were monitored by people.The grass-roots medi-cal institutions had the highest requirements for various professional trainings and increase of training contents of prevention and control of public health infectious diseases(100.00%).The county-level medical institutions had inadequate capabilities of professional examination of medical equipment replacement and construction of medi-cal architecture.CONCLUSION It is necessary for the country and local levels of governments to attach great importance to the implementation of the infection control core elements in the grass-roots medical institutions within the county-lev-el medical communities,establish the county-level regional information platform,formulate the corresponding surveil-lance indexes and homogenized management systems,complete the cultivation of talents,and offer financial support.
6.A study on the distribution patterns of traditional Chinese medicine syndrome types in antipsychotic-induced metabolic syndrome
Shulian XIAN ; Hongxiao JIA ; Xue LI ; Di WANG ; Mingkang SONG ; Dongqing YIN ; Hairong JIANG
Journal of Capital Medical University 2025;46(3):463-470
Objective To explore the distribution patterns of traditional Chinese medicine(TCM)syndromes in patients with metabolic syndrome caused by antipsychotic drugs.Methods A standardized TCM syndrome survey was performed to collect diagnostic information from 160 patients diagnosed with metabolic syndrome due to antipsychotic drug use.Subsequent frequency analysis,cluster analysis,and Bayesian network analysis were carried out.The syndrome pattern distribution was ultimately determined through relevant literatures and expert opinions.Results Five TCM syndromes were identified through frequency,cluster,and Bayesian network analyses.The most common syndrome was qi deficiency with phlegm-dampness(30%),followed by spleen deficiency with phlegm-Heat(23.75%),qi and yin deficiency Pattern(21.88%),yin deficiency with damp-heat(17.50%),and stomach fire hyperactivity pattern(6.88%).Conclusion The pathogenesis of antipsychotics-induced metabolic syndrome involves a complex interplay of deficiency and excess factors.The primary disease is mainly located at the spleen and stomach,with involvement of the liver,kidney,and heart.Pathogenic factors include qi deficiency,yin deficiency,dampness,heat,pathogenic fire,and phlegm.
7.Systematic review of risk prediction models for enteral feeding intolerance in ICU patients
Yubing LI ; Qian LU ; Fan LI ; Lichuan ZHANG ; Xiaoge HE ; Aihui LIU ; Longfei YANG ; Di JIANG
Chinese Journal of Modern Nursing 2025;31(13):1705-1712
Objective:To conduct a systematic review of risk prediction models for enteral feeding intolerance in ICU patients.Methods:Relevant literature was searched in China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc, VIP, PubMed, Web of Science, Cochrane Library, Embase, CINAHL, and Scopus, with search limits from the establishment of the databases up to July 24, 2024. Two researchers independently screened the literature and extracted data, using Prediction model Risk Of Bias ASsessment Tool to evaluate the quality of the included studies.Results:A total of 12 studies were included, which included 20 prediction models. The area under the receiver operating characteristic curve or C-index for these models ranged from 0.70 to 0.94. The overall bias risk of the 12 studies was high, with three studies having good applicability. The bias risk primarily stemmed from issues such as measurement of prediction factors, variable handling, sample size, outcome definition, and model performance evaluation.Conclusions:Existing risk prediction models for enteral feeding intolerance in ICU patients exhibit a high risk of bias. Further validation, optimization, or development of new models is required in the future.
8.Quality inspection of ultrasound soft tissue cutting hemostatic equipment
Jing HUANG ; Qi-di SUN ; Ao-wen DUAN ; Li XU ; Heng-yu LONG ; Hai-jiang ZHU ; He-hua ZHANG
Chinese Medical Equipment Journal 2025;46(10):49-53
Objective To carry out quality inspection of the ultrasound soft tissue cutting hemostatic equipment to ensure its safety and effectiveness.Methods Five brands of ultrasound soft tissue cutting hemostatic equipment were selected and noted as test equipment A,test equipment B,test equipment C,test equipment D and test equipment E,which underwent quality inspection in terms of tip main amplitude,tip lateral amplitude,tip vibration frequency,excitation frequency,static electrical power and contact current based on YY/T 0644-2008 Ultrasonics-surgical systems—Measurement and declaration of the basic output characteristics,YY/T 1750-2020 Ultrasonic surgical equipmetn for soft tissue excision and hemostasia and GB 9706.1-2020 Medical electrical equipment—Part 1:General requirements for basic safety and essential performance.Results The test data of the five brands in terms of tip main amplitude,tip lateral amplitude,tip vibration frequency,excitation frequency,static electrical power and contact current met the technical requirements of YY/T 0644-2008,YY/T 1750-2020,GB 9706.1-2020.Conclusion The quality inspection of the ultrasound soft tissue cutting hemostatic equipment contributes to enhancing the accuracy and stability of the equipment and decreasing the risk during its clinical application.[Chinese Medical Equipment Journal,2025,46(10):49-53]
9.Role of fibrinogen in perioperative neurocognitive disorder in aged mice
Xueji WANG ; Sufang JIANG ; Jiaqi LI ; Lichao DI ; Peiying HUANG ; Tianyu CAO ; Lining HUANG
Chinese Journal of Anesthesiology 2025;45(2):156-162
Objective:To evaluate the role of fibrinogen in perioperative neurocognitive disorder (PND) in aged mice.Methods:Sixty SPF healthy male C57BL/6J mice, aged 16-18 months, weighing 25-30 g, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), PND group (group P), urokinase group (group U) and PND+ urokinase group (group PU). Abdominal surgery was performed under 3% sevoflurane anesthesia to establish the mouse model of PND. In PU group, urokinase 20 000 U/kg was intraperitoneally administered at 1 h after surgery, once a day, for 5 consecutive days. In group U, urokinase was intraperitoneally injected once a day for 5 consecutive days without anesthesia and surgery. The cognitive function was assessed after operation using the novel object recognition test (discrimination index) and the Morris water maze test (frequency of crossing the original platform and percentage of the time spent in the target quadrant). The expression of occludin, claudin-5, fibrinogen and ionized calcium-binding adapter molecule 1 (Iba-1) and CD11b in hippocampal tissues was detected using Western blot, the area of fibrinogen extravascular deposits was measured and the morphology of microglia was observed using the immunofluorescence staining, and the mRNA expression of pro-inflammatory factors (interleukin-1beta, tumor necrosis factor-alpha, and inducible nitric oxide synthase), anti-inflammatory factors (interleukin-4 and arginase-1), and chemokines (chemokine 2 and chemokine ligand 10) in hippocampal tissues was detected by quantitative real-time polymerase chain reaction after surgery. Results:Compared with group C, the parameters of cognitive function were significantly decreased, the expression of occludin and claudin-5 was down-regulated, the expression of fibrinogen was up-regulated, the area of fibrinogen extravascular deposits was increased, the number of branches was decreased and the average process length was shortened in the microglia around fibrinogen deposits, the expression of Iba-1 and CD11b was up-regulated, the mRNA expression of proinflammatory cytokines and chemokines was up-regulated, and the mRNA expression of the anti-inflammatory factors was down-regulated in group PND ( P<0.05). Compared with group PND, the parameters of cognitive function were significantly increased, the expression of occludin and claudin-5 was up-regulated, the expression of fibrinogen was down-regulated, the area of fibrinogen extravascular deposits was decreased, the number of branches was increased and the average process length was prolonged in the microglia around fibrinogen deposits, the expression of Iba-1 and CD11b was down-regulated, the mRNA expression of proinflammatory cytokines and chemokines was down-regulated, and the mRNA expression of the anti-inflammatory factors was up-regulated in group PU ( P<0.05). Conclusions:Fibrinogen deposits in the brain parenchyma through the damaged blood-brain barrier after anesthesia and surgery and participates in the development of PND, and the underlying mechanism may be related to the promotion of microglial activation and the induction of neuroinflammation in aged mice.
10.Mechanism of ω-3 polyunsaturated fatty acids preventing sevoflurane-induced neurotoxicity in neonatal mice: phosphorylated Tau glymphatic system clearance pathway
Tianyu CAO ; Lichao DI ; Peiying HUANG ; Longlu CAO ; Sufang JIANG ; Xueji WANG ; Jiaqi LI ; Lining HUANG
Chinese Journal of Anesthesiology 2025;45(2):170-177
Objective:To evaluate the relationship between the mechanism of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) preventing sevoflurane-induced neurotoxicity and phosphorylated Tau glymphatic system clearance pathway in neonatal mice.Methods:Eighteen C57BL/6 pregnant mice were used in this study and subjected to 2 feeding regiments using the random number table method. Twelve mice were selected to receive a standard diet, and 6 mice were selected to receive a diet supplemented with fish oil (ω-3 polyunsaturated fatty acids [300 mg was added to every 20 g of standard diet from the 2nd day of gestation to 14 days after parturition). The healthy neonatal mice of both sexes, aged 6 days, weighing 3-5 g, were selected after parturition. Forty-eight neonatal pups from 6 pregnant mice that were fed a standard diet were assigned to control group (C group), 48 neonatal pups from 6 pregnant mice that were fed a standard diet were assigned to sevoflurane group (S group), and 48 neonatal pups from pregnant mice that were fed a diet supplemented with fish oil were assigned to ω-3 PUFAs plus sevoflurane group (PS group) using the random number table method. All the offspring mice in all groups were breastfed until 21 days of birth and then were housed in separate cages from their mothers after 21 days of birth and provided with ad libitum access to standard food. S group and PS group inhaled 3% sevoflurane and 40% oxygen for 2 h daily on postnatal days 6, 7 and 8. C group inhaled only 40% oxygen at the same flow rate. Y maze test was performed at postnatal day 33 to assess the spatial memory and cognitive function. The rotarod test was performed at postnatal day 35 to assess the fine motor coordination. The influx and efflux functions of the glymphatic system were assessed through intracisternal tracer infusion with the fluorescent tracer at postnatal days 14 and 35. The influx function was evaluated by the percentage of the area of tracer penetration 30 min after injection, while the efflux function was determined by the percentage of the residual area of the tracer 90 min after injection. The mice were sacrificed and the hippocampal tissue was obtained at postnatal day 14 for determination of the expression of phosphorylated Tau protein at serine 202 site and threonine 205 site (Tau-PS202/PT205) and total Tau protein by Western blot. The cerebrospinal fluid (CSF) was collected at postnatal day 14 for determination of the concentration of phosphorylated Tau protein by enzyme-linked immunosorbent assay. The mice were sacrificed and the hippocampal tissue was obtained at postnatal day 35 for determination of the expression of caspase-3, caspase-9 and cytochrome C (Cyt c) (by Western blot) and the apoptosis rate of neurons (by TUNEL).Results:Compared with C group, the time of staying at the new arm and in the rotarod test was significantly shortened, the percentage of new arm movement distance was decreased, the percentage of tracer penetration area was decreased at postnatal day 14, the percentage of residual tracer area was increased at postnatal day 14, the expression of Tau-PS202/PT205 in the hippocampus was up-regulated at postnatal day 14, the concentration of phosphorylated Tau protein in CSF was reduced at postnatal day 14, the apoptosis rate of hippocampal neurons was increased at postnatal day 35 ( P<0.05), and the expression of caspase-3, caspase-9 and Cyt c in the hippocampus was up-regulated at postnatal day 35 in S group ( P<0.05). Compared with S group, the time of staying at the new arm and in the rotarod test was significantly prolonged, the percentage of new arm movement distance was increased, the percentage of tracer penetration area was increased at postnatal day 14, the percentage of residual tracer area was decreased at postnatal day 14, the expression of Tau-PS202/PT205 in the hippocampus was down-regulated at postnatal day 14, the concentration of phosphorylated Tau protein in CSF was increased at postnatal day 14, the apoptosis rate of hippocampal neurons was decreased at postnatal day 35, and the expression of caspase-3, caspase-9 and Cyt c in the hippocampus was down-regulated at postnatal day 35 in PS group ( P<0.05). Conclusions:The mechanism by which ω-3 PUFAs prevents cerebral neurotoxicity induced by repeated neonatal sevofurane exposure may be related to the enhancement of phosphorylated Tau protein clearance via the glymphatic system.

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