1.Pharmacological inhibition of ENaC or NCX can attenuate hepatic ischemia-reperfusion injury exacerbated by hypernatremia.
Yabin CHEN ; Hao LI ; Peihao WEN ; Jiakai ZHANG ; Zhihui WANG ; Shengli CAO ; Wenzhi GUO
Journal of Zhejiang University. Science. B 2025;26(5):461-476
Donors with a serum sodium concentration of >155 mmol/L are extended criteria donors for liver transplantation (LT). Elevated serum sodium of donors leads to an increased incidence of hepatic dysfunction in the early postoperative period of LT; however, the exact mechanism has not been reported. We constructed a Lewis rat model of 70% hepatic parenchymal area subjected to ischemia-reperfusion (I/R) with hypernatremia and a BRL-3A cell model of hypoxia-reoxygenation (H/R) with high-sodium (HS) culture medium precondition. To determine the degree of injury, biochemical analysis, histological analysis, and oxidative stress and apoptosis detection were performed. We applied specific inhibitors of the epithelial sodium channel (ENaC) and Na+/Ca2+ exchanger (NCX) in vivo and in vitro to verify their roles in injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels and the area of hepatic necrosis were significantly elevated in the HS+I/R group. Increased reactive oxygen species (ROS) production, myeloperoxidase (MPO)-positive cells, and aggravated cellular apoptosis were detected in the HS+I/R group. The HS+H/R group of BRL-3A cells showed significantly increased cellular apoptosis and ROS production compared to the H/R group. The application of amiloride (Amil), a specific inhibitor of ENaC, reduced ischemia-reperfusion injury (IRI) aggravated by HS both in vivo and in vitro, as evidenced by decreased serum transaminases, inflammatory cytokines, apoptosis, and oxidative stress. SN-6, a specific inhibitor of NCX, had a similar effect to Amil. In summary, hypernatremia aggravates hepatic IRI, which can be attenuated by pharmacological inhibition of ENaC or NCX.
Animals
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Reperfusion Injury/drug therapy*
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Hypernatremia/complications*
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Rats
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Liver/metabolism*
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Rats, Inbred Lew
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Male
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Apoptosis
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Sodium-Calcium Exchanger/antagonists & inhibitors*
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Reactive Oxygen Species/metabolism*
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Oxidative Stress
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Epithelial Sodium Channel Blockers/pharmacology*
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Epithelial Sodium Channels
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Cell Line
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Liver Transplantation
2.Assessment of perioperative pulmonary fluid volume using remote dielectric sensing (ReDSTM) non-invasive lung fluid measurement technology in transcatheter tricuspid valve-in-valve implantation: The first case report
Yuliang LONG ; Yuan ZHANG ; Xiaochun ZHANG ; Peng WANG ; Xiaotong CUI ; Wenzhi PAN ; Daxin ZHOU ; Junbo GE
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(04):571-574
One of its primary surgical treatments of tricuspid regurgitation is tricuspid valve biological valve replacement. Catheter tricuspid valve-in-valve implantation is a novel interventional alternative for biological valve failure. The non-invasive lung fluid measuring device remote dielectric sensing (ReDSTM) has been increasingly incorporated into clinical practice as a means of monitoring chronic heart failure in recent years. This report describes the process and outcomes of the first instance of perioperative lung fluid volume evaluation following transcatheter tricuspid valve implantation utilizing ReDSTM technology. The patient has a short-term, substantial increase in postoperative lung fluid volume as compared to baseline.
3.Consensus on diagnosis and treatment of adolescent idiopathic scoliosis
Yushu BAI ; Kai CHEN ; Jie SHAO ; Xiao ZHAI ; Ming CHEN ; Weishi LI ; Jianzhong XU ; Bangping QIAN ; Zezhang ZHU ; Feng ZHU ; Chunde LI ; Jianguo ZHANG ; Jianxiong SHEN ; Dingjun HAO ; Xiaodong ZHU ; Junlin YANG ; Xuejun ZHANG ; Xuesong ZHANG ; Fangyi ZHANG ; Qijie WANG ; Wenzhi ZHANG ; Yong HAI ; Jianhua ZHAO ; Yong QIU ; Yan WANG ; Guixing QIU ; Ming LI
Academic Journal of Naval Medical University 2025;46(3):291-300
Adolescent idiopathic scoliosis(AIS)is a complex three-dimensional deformity involving coronal,sagittal,and axial planes,with a prevalence that should not be overlooked.With advancements in technology and in-depth research,an increasing number of hospitals and physicians are exploring standardized diagnostic and treatment approaches for AIS.Comprehensive and in-depth understanding is required for AIS,including its etiology,screening and diagnosis,classification,assessment and examination,treatment options,exploration of current focus,and evaluation of quality of life.Such understanding ensures that the diagnostic and treatment are scientific,standardized,and timely.Based on the principles of evidence-based medicine,a consensus on the diagnosis and treatment of AIS is reached after multiple discussions among spinal surgery experts,aiming to provide reference and guidance for clinical practice.
4.Integration of deep neural network modeling and LC-MS-based pseudo-targeted metabolomics to discriminate easily confused ginseng species.
Meiting JIANG ; Yuyang SHA ; Yadan ZOU ; Xiaoyan XU ; Mengxiang DING ; Xu LIAN ; Hongda WANG ; Qilong WANG ; Kefeng LI ; De-An GUO ; Wenzhi YANG
Journal of Pharmaceutical Analysis 2025;15(1):101116-101116
Metabolomics covers a wide range of applications in life sciences, biomedicine, and phytology. Data acquisition (to achieve high coverage and efficiency) and analysis (to pursue good classification) are two key segments involved in metabolomics workflows. Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups. However, insufficient feature extraction, inappropriate feature selection, overfitting, or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused. Using two ginseng varieties, namely Panax japonicus (PJ) and Panax japonicus var. major (PJvm), containing the similar ginsenosides, we integrated pseudo-targeted metabolomics and deep neural network (DNN) modeling to achieve accurate species differentiation. A pseudo-targeted metabolomics approach was optimized through data acquisition mode, ion pairs generation, comparison between multiple reaction monitoring (MRM) and scheduled MRM (sMRM), and chromatographic elution gradient. In total, 1980 ion pairs were monitored within 23 min, allowing for the most comprehensive ginseng metabolome analysis. The established DNN model demonstrated excellent classification performance (in terms of accuracy, precision, recall, F1 score, area under the curve, and receiver operating characteristic (ROC)) using the entire metabolome data and feature-selection dataset, exhibiting superior advantages over random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and multilayer perceptron (MLP). Moreover, DNNs were advantageous for automated feature learning, nonlinear modeling, adaptability, and generalization. This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples. This established approach holds promise for plant metabolomics and is not limited to ginseng.
5.Integration of deep neural network modeling and LC-MS-based pseudo-targeted metabolomics to discriminate easily confused ginseng species
Meiting JIANG ; Yuyang SHA ; Yadan ZOU ; Xiaoyan XU ; Mengxiang DING ; Xu LIAN ; Hongda WANG ; Qilong WANG ; Kefeng LI ; De-An GUO ; Wenzhi YANG
Journal of Pharmaceutical Analysis 2025;15(1):126-137
Metabolomics covers a wide range of applications in life sciences,biomedicine,and phytology.Data acquisition(to achieve high coverage and efficiency)and analysis(to pursue good classification)are two key segments involved in metabolomics workflows.Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups.However,insufficient feature extraction,inappropriate feature selection,overfitting,or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused.Using two ginseng varieties,namely Panax japonicus(PJ)and Panax japonicus var.major(PJvm),containing the similar ginsenosides,we integrated pseudo-targeted metabolomics and deep neural network(DNN)modeling to achieve accurate species differentiation.A pseudo-targeted metabolomics approach was optimized through data acquisition mode,ion pairs generation,comparison between multiple reaction monitoring(MRM)and scheduled MRM(sMRM),and chromatographic elution gradient.In total,1980 ion pairs were monitored within 23 min,allowing for the most comprehensive ginseng metabolome analysis.The established DNN model demonstrated excellent classification performance(in terms of accuracy,precision,recall,F1 score,area under the curve,and receiver operating characteristic(ROC))using the entire metabolome data and feature-selection dataset,exhibiting superior advantages over random forest(RF),support vector ma-chine(SVM),extreme gradient boosting(XGBoost),and multilayer perceptron(MLP).Moreover,DNNs were advantageous for automated feature learning,nonlinear modeling,adaptability,and generalization.This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples.This established approach holds promise for plant metabolomics and is not limited to ginseng.
6.Etiology,pathogenesis,syndrome differentiation,and treatment of neuro-endocrine-immune system imbalance in depression based on the"excessive vitality leading to restraint and counter-regulation(Kang Hai Cheng Zhi)"theory
Jiaxi TONG ; Yidi WANG ; Aixin LI ; Yanru SUN ; Wenzhi HAO ; Zhe XUE ; Yueyun LIU ; Yueyue CHEN ; Jiaxu CHEN
Journal of Beijing University of Traditional Chinese Medicine 2025;48(7):903-908
Depression is closely associated with a neuro-endocrine-immune(NEI)system imbalance.The"excessive vitality leading to restraint and counter-regulation(Kang Hai Cheng Zhi)"theory elucidates the self-regulating mechanism for maintaining dynamic equilibrium in the body,and serves as an importance principle guiding treatment formulation and medication selection.Based on the correlation between NEI system imbalance and the traditional Chinese medicine pathogenesis of depression,and integrating the"Kang Hai Cheng Zhi"theory,the author posits that the pathogenesis of depression lies in overactive liver invading spleen,earth dampness impeding wood′s ascendancy,and disharmony between body and mind,as well as imbalance in storage and discharge functions of liver and kidney,disharmony between Yin and Yang,and disrupted counter-regulation.This dosely aligns with two key pathological methanisms at the micro level:microglial-limbic system homeostatic imbalance and hypothalamic-pituitary-adrenal axis-inflammatory circuit dysregulation.Clinically,the treatment principle for depression adheres to supporting the counter-regulation to restrain excess,with herbal interventions using strategies such as restraining wood to support earth,dredging earth to unblock wood,and harmonizing pivotal functions,as well as nourishing water to nurture wood,warming kidney to tonify liver,and relieving depression to calm the spirit.These approaches aim to regulate the liver,spleen,and kidney,embodying the core therapeutic tenet of"striving for equilibrium,"thereby restoring the body′s self-regulating capability.
7.Effects of deep hyperthermia on immune function during postoperative adjuvant chemotherapy in patients with colorectal cancer
Lei ZHAO ; Hongbo WANG ; Wenzhi LIU ; Feng LIN ; Jian YU ; Mingjun SUN ; Baosheng YU ; Yunxiao ZHONG ; Yougang CUI ; Xu ZHANG ; Yupeng YI ; Na WANG ; Daocheng WU ; Chenyang LI ; Pan HU ; Ning FENG
Chinese Journal of Radiation Oncology 2025;34(5):461-467
Objective:To explore the effects of deep hyperthermia on chemotherapy-related adverse effects and immune-inflammatory indicators in the patients undergoing postoperative adjuvant chemotherapy for colorectal cancer.Methods:This retrospective study included 52 patients who underwent surgery for colorectal cancer at the Affiliated Zhongshan Hospital of Dalian University from September 2021 to December 2023. The patients were divided into two groups based on treatment method: the combination group ( n=29) received postoperative adjuvant chemotherapy combined with deep hyperthermia, while the chemotherapy group ( n=23) received postoperative adjuvant chemotherapy alone. Both groups were treated with the XELOX regimen (oxaliplatin + capecitabine). The degree of bone marrow suppression during treatment was assessed by analyzing peripheral blood parameters, including hemoglobin, leukocyte count, neutrophil count, and platelet count. Immune-inflammatory indicators, including complement, procalcitonin (PCT), interleukin-6 (IL-6), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), were compared before and after treatment in both groups to evaluate the effects of deep hyperthermia on the immune-inflammatory response. Chi-square test or Fisher's exact test (two-tailed) was used to compare bone marrow suppression rates, and the immune-inflammatory indicators between the two groups were compared using t-tests or non-parametric tests, depending on whether the data conformed to a normal distribution. Results:In terms of myelosuppression, the incidence rates of moderate to severe decreases in leukocytes, neutrophils, platelets, and hemoglobin in the combination group were 31%, 31%, 21%, and 14%, respectively, compared to 52%, 61%, 48%, and 9% in the chemotherapy group. The change in PCT levels before and after treatment was significantly greater in the combination group than in the chemotherapy group ( P = 0.010). Both the combination group and the chemotherapy group showed significant reductions in SII, NLR and PLR after treatment, and the differences were statistically significant (all P < 0.05). The change in NLR before and after treatment was significantly greater in the combination group than in the chemotherapy group ( P = 0.031). Conclusions:Deep hyperthermia can alleviate chemotherapy-induced adverse effects such as thrombocytopenia and neutropenia in patients undergoing postoperative adjuvant chemotherapy for colorectal cancer. It also appears to improve the inflammatory response in these patients.
8.Comparative study on replacing Wnt3a with small molecule compound CHIR99021 in colorectal cancer organoid culture
Run LI ; Feng LIN ; Ruoyu WANG ; Wenzhi LIU ; Shanshan LIANG
Chinese Journal of Digestion 2025;45(6):393-400
Objective:To compare the efficacy of Wnt3a factor and small molecule compound CHIR99021 in culturing colorectal cancer organoid, and to explore the feasibility of replacing Wnt3a with CHIR99021.Methods:The organoids were cultured using 2 culture systems containing Wnt3a or CHIR99021, based on the colorectal cancer cell line HCT116 and rectal cancer tissue from one patient (surgical specimen from the Department of Gastrointestinal Surgery, Zhongshan Hospital Affiliated to Dalian University), including Wnt3a cell organoid, CHIR99021 cell organoid, Wnt3a tissue organoid, and CHIR99021 tissue organoid. The growth of organoids was observed under the optical microscope. The pathological characteristics of organoids and the rectal cancer tissue were analyzed by hematoxylin-eosin (HE) staining and immunohistochemical (IHC) staining, which included cytokeratin(CK) 7, CK20, Ki-67, and stemness marker CD133. The expression of β-catenin (a key Wnt pathway protein) was analyzed by Western blotting (WB) method. The half maximal inhibitory concentration (IC50) values of Wnt3a and CHIR99021 cell organoids were analyzed by drug susceptible test and GraphPad Prism 9.0 software. Independent sample- t test was used for statistical analysis. Results:Under the optical microscope, the size of CHIR99021 cell organoid was relatively uniform, while the size of the Wnt3a cell organoid was uneven, compact and dense spherical structure was formed in both organoids. HE staining showed tumor features including increased nuclear-cytoplasmic ratio and obvious nuclear atypia in the Wnt3a and CHIR99021 cell organoids. The results of IHC staining showed that CK7 was negative, and CK20 and Ki-67 were positive in the Wnt3a and CHIR99021 cell organoids. The results of WB method showed that the relative expression level of β-catenin of the CHIR99021 cell organoid was higher than that of the Wnt3a cell organoid (0.89±0.09 vs. 0.26±0.04), and the difference was statistically significant ( t=13.80, P<0.001). The results of drug susceptible test demonstrated that the IC50 value of the Wnt3a and CHIR99021 cell organoid was 10.91 and 14.55 μmol/L, respectively. Further IHC staining showed that CD133 was positive in the Wnt3a and CHIR99021 cell organoids, with stronger intensity in the CHIR99021 cell organoid. The pathological characteristics of Wnt3a and CHIR99021 tissue organoid were consistent with those of the rectal cancer tissue of the patient, with all CK7 being negative and CK20 and Ki-67 being positive. Conclusions:Both Wnt3a and CHIR99021 can successfully establish colorectal cancer organoids with consistent pathological characteristics. The IC50 value of the CHIR99021 cell organoid is high, which is related to the increased stemness of organoids. The pathological characteristics of Wnt3a and CHIR99021 tissue organoid are consistent with those of the rectal cancer tissue from the patient.
9.A cohort study and Mendelian randomization study on association between osteoporosis and Alzheimer's disease
Xuan WU ; Xunying ZHAO ; Jinyu ZHOU ; Tao HAN ; Xia JIANG ; Ben ZHANG ; Wenzhi WANG
Chinese Journal of Epidemiology 2025;46(5):888-894
Objective:To analyze the association between osteoporosis and the risk for Alzheimer's disease (AD).Methods:A total of 471 922 study subjects were selected from the UK Biobank database, including 12 818 osteoporosis cases and 459 104 controls. Cox proportional hazard regression model and competing risk model were used to evaluate the association between osteoporosis and AD after adjusting confounding factors. Furthermore, a Mendelian randomization (MR) study was conducted by using the data of two published genome-wide association studies, and 1 050 highly relevant single nucleotide polymorphisms were identified from the bone mineral density data as instrumental variables. The association between bone mineral density and the risk for AD was evaluated by using inverse variance weighted method, MR-Egger regression, and weighted median estimator method. Additionally, sensitivity analyses were performed.Results:After adjusting for confounders, no significant association between osteoporosis and an increased risk for AD was found in the cohort study (Cox proportional hazard regression model analysis: HR=1.10, 95% CI: 0.78-1.56, P=0.588). The MR analysis revealed no association between bone mineral density and the risk for AD (inverse-variance weighted: OR=1.03, 95% CI: 0.98-1.09, P=0.252), and the results remained robust in multiple sensitivity analyses. Conclusion:The study result does not support the association between osteoporosis and risk for AD.
10.Effects of remote ischemic preconditioning on myocardial injury after non-cardiac surgery in elderly patients with hip fracture
Yangchunxue LI ; Jie GAO ; Zhicheng ZHANG ; Chun BAI ; Dongdong LYU ; Xuemei HAO ; Xiaowei WANG ; Zhi LIU ; Wenzhi GUO
Chinese Journal of Trauma 2025;41(6):565-571
Objective:To investigate the effects of remote ischemic preconditioning (RIPC) on myocardial injury after non-cardiac surgery (MINS) in elderly patients with hip fracture.Methods:A prospective randomized controlled trial was conducted on 78 elderly patients with hip fracture admitted to the Seventh Medical Center of the PLA General Hospital between October 2023 and September 2024. The patients were divided into RIPC group and non-RIPC group using a random number table. They were treated with closed reduction internal fixation, open reduction internal fixation, or hip arthroplasty for hip fracture under regional anesthesia. The RIPC group received RIPC intervention on the day before surgery and after entering the operating room on the day of surgery (3 cycles of 5-minute upper limb exsanguination followed by 5-minute reperfusion using an inflatable tourniquet cuff). The non-RIPC group received the same perioperative management as the RIPC group except RIPC. Plasma high-sensitivity cardiac troponin I (hs-cTnI) concentrations were measured at admission, immediately after surgery, on the morning of the first postoperative day, and on the morning of the third postoperative day and MINS incidence was calculated based on the hs-cTnI concentrations. The incidence of MINS within 3 days postoperatively and the intraoperative complications were compared in the overall cohort and in age-stratified groups (<80 years, ≥80 years). The local adverse reactions at the RIPC application sites were observed within 3 days after surgery.Results:Among the 78 elderly patients with hip fracture, including 21 males and 57 females, aged 60-99 years [79.5(70.0, 87.0)years], 40 were assigned to the RIPC group and 38 to the non-RIPC group. No significant difference was found in the general data of the two groups. There was no significant difference in the overall MINS incidence between the two groups ( P>0.05). In the patients aged <80 years, no MINS incidence was found (0/21) in the RIPC group, compared with 22% (4/18) in the non-RIPC group ( P<0.05), while in the patients aged ≥80 years, no significant difference in MINS incidence was observed between the two groups ( P>0.05). There were no significant differences in intraoperative complication rates in the overall cohort, patients aged <80 years, or patients aged ≥80 years ( P>0.05). None of the patients had local adverse reactions at the RIPC application sites. Conclusion:For elderly patients with hip fracture who received regional anesthesia, RIPC can significantly reduce the incidence of MINS in patients aged <80 years, but exerts no significant effect on MINS incidence in the overall cohort or in patients aged ≥80 years.

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