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*
;
Hypernatremia/complications*
;
Rats
;
Liver/metabolism*
;
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.Low-intensity pulsed ultrasound and oridonin synergistically induce ferroptosis of pancreatic cancer cells by activating PIEZO1 via the Nrf2/HO-1/GPX4 pathway.
Bihang SUN ; Yujun GUO ; Yulin QI ; Dan YAO ; Wenzhi CHEN ; Nianzhi CHEN
Journal of Southern Medical University 2025;45(10):2160-2170
OBJECTIVES:
To evaluate the inhibitory effect of oridonin against proliferation of pancreatic cancer cells and the mechanism underlying the synergistic effect of low-intensity pulsed ultrasound (LIPUS).
METHODS:
PANC-1 cells treated with different concentrations of oridonin were examined for changes in cell proliferation using CCK-8 assay and in MDA, GSH and ATP levels using flow cytometry. The protein expressions of GPX4, Nrf2 and HO-1 in the treated cells were detected with Western blotting. The effect of Fer-1, a ferroptosis inhibitor, on proliferation of oridonin-treated cells were assessed, and the effects of oridonin combined with LIPUS on PIEZO1 protein expression was evalauted using Western blotting. A C57BL/6J mouse model bearing pancreatic cancer cell xenograft was established and treated with oridonin, LIPUS, or both, and the histological changes in the tumor tissues and tumor cell proliferation were examined with HE staining and immunohistochemistry for Ki67; the changes in GPX4 expression in the tumor tissues were detected using Western blotting and immunofluorescence staining.
RESULTS:
In PANC-1 cells, oridonin treatment significantly inhibited cell proliferation, increased intracellular Fe2+, ROS, and MDA levels, and decreased GSH and ATP levels. Oridonin also resulted in lowered GPX4 and increased HO-1 and Nrf2 protein expression levels in the cells. The combined treatment with LIPUS signficiantly enhanced the inhibitory effect of oridonin on PANC-1 cell viability in vitro and on xenograft growth in the mouse models, resulting also in more obvious reduction of the intensity of Ki67 staining and GPX4 protein expression and more pronounced increase of PIEZO1 protein expression in the tumor tissues in the mouse models.
CONCLUSIONS
LIPUS enhances the effect of oridonin to promote ferroptosis of pancreatic cancer cells by activating PIEZO1 through the Nrf2/HO-1/GPX4 pathway.
Ferroptosis/drug effects*
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Animals
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Pancreatic Neoplasms/metabolism*
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NF-E2-Related Factor 2/metabolism*
;
Humans
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Cell Line, Tumor
;
Mice
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Heme Oxygenase-1/metabolism*
;
Diterpenes, Kaurane/pharmacology*
;
Cell Proliferation/drug effects*
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Mice, Inbred C57BL
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Phospholipid Hydroperoxide Glutathione Peroxidase
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Ion Channels/metabolism*
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Ultrasonic Waves
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Signal Transduction
3.Yishi Therapy for the Treatment of Primary Tinnitus:A Long-Term Efficacy Follow-up of 496 Cases
Yanfang CHEN ; Peng LIU ; Wenzhi LIN ; Jinguang LIU ; Jieheng LIU ; Haixin ZHANG ; Weiping HE
Journal of Traditional Chinese Medicine 2024;65(24):2558-2564
ObjectiveTo demonstrate the long-term effect of Yishi Therapy for primary tinnitus and analyze the factors affecting the effectiveness. MethodsWe conducted long-term follow-ups of primary tinnitus cases treated with Yishi Therapy during 1 January 2017 to 30 June 2023 by face-to-face, online and telephone between 1 July 2023 and 31 January 2024, to understand the final regression of primary tinnitus and lifestyle changes. We retrospectively analysed the basic data of patients before treatment, and statistically analysed the recovery rate and overall effective rate of tinnitus treated by the Yishi Therapy, and the factors affecting the effectiveness such as lifestyle, age, duration of disease, gender, tinnitus location, severity of tinnitus, accompanying symptoms and complications on the overall effective rate. ResultsA total of 496 cases of primary tinnitus completed follow-ups successfully, and the total Tinnitus Evaluation Questionnaire (TEQ) at follow-up was significantly lower than that before treatment (P<0.001). Among the 496 cases, 101 (20.36%) cases cured, 189 (38.10%) cases showed significant improvement, 116 (23.39%) cases were effective, 90 (18.15%) cases were ineffective, and the overall effect rate was 81.85% (406/496). At follow-up, the score of lifestyle was higher than that before treatment (P<0.001). Grouped by the score of lifestyle at follow-up, the effective rates of better lifestyle group and poor lifestyle group were 97.53% (237/243) and 66.80% (169/253), respectively, with statistical significance (P<0.001). Grouped by the mean value of the difference in lifestyle scores before and after treatment, the effective rates of the group with greater lifestyle adjustment and the group with smaller adjustment were 97.55% (239/245) and 66.53% (167/251), respectively, and the differences were statistically significant (P<0.001). Binary logistic regression showed that the better lifestyle, the greater lifestyle adjustment and the severity of tinnitus were positively correlated with the total effective rate of tinnitus (P<0.001), while older and hearing loss were negatively correlated with the total effective rate of tinnitus (P<0.05). ConclusionYishi Therapy on primary tinnitus shows good long-term effect, lifestyle, severity of tinnitus, hearing loss or not, age are the relevant factors affecting the efficacy of tinnitus, lifestyle is the main factor affecting clinical efficacy.
4.Developing the Risk Nomogram Model of Low Triiodothyronine Syndrome in Elderly Patients with Chronic Heart Failure
Xiaoli FENG ; Zhenhua LI ; Huimin CHEN ; Wenzhi XIE ; Liliang CHEN
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(5):844-852
[Objective]The clinical characteristics and the possible risk factors were explored for the low triiodothyronine syndrome(LTS)in elderly patients with chronic heart failure(CHF),and the risk prediction model of LTS was established.[Methods]For this research,291 elderly patients with CHF were selected as sample and retrospectively reviewed was used as analytical method.According to the thyroid function of admission patients,two groups including LTS group(n=107)and normal thyroid function group(n=184)were divided.The general information and biochemical indicators of patients were collected and recorded,and the risk factors for LTS were assigned scores,in which numerical variables(except age)were grouped by median.The chi-squared test was used for statistical analysis of each variable,and multivariate regression model was used to analyze the independent risk factors of LTS in elderly patients with CHF,then the nomogram model for LTS was established based on the results from the final regression analysis.Furthermore,the prediction model was evaluated using C-index,calibration curve and receiver operating characteristic(ROC)curve.[Result]Serum creatinine(Scr),C-reactive protein(CRP),interleukin-6(IL-6)and the cardiac functional grading according to the New York Heart Association(NYHA)were positively correlated with LTS(OR values were 1.893,2.356,1.021 and 1.815,respectively,P<0.05),serum Albumin(Alb)was negatively correlated with LTS(OR=0.412,P<0.05).This means that,the LTS was easily occurred as the serum Alb level declined.When introduce the above statistically significant variables into nomogram obtained the C index with 0.807[95%CI=(0.757,0.856)].The calibration curve verified by internal verification showed that the calibration degree of this prediction model was well calibrated.ROC curve analysis showed that the prediction model was well differentiated.[Conclusion]The Scr,CRP,IL-6,Alb and cardiac functional grading in elderly CHF patients may be risk factors for incidence of LTS,while serum Alb may be a protective factor for LTS.Based on the above risk factors,the nomogram model for predicting the occurrence of LTS in elderly CHF patients had good differentiation and accuracy,and can provide guidance for clinical individualized prevention and treatment.
5.Development of microsatellite markers and analysis of genetic characteristics of laboratory Apodemus peninsulae population
Qing ZHANG ; Xiwen ZHANG ; Song HE ; Bao YUAN ; Jian CHEN ; Wenzhi REN ; Fushi QUAN ; Jinping HU ; Yu DING
Acta Laboratorium Animalis Scientia Sinica 2024;32(4):468-476
Objective Polymorphic microsatellite markers developed for Apodemus peninsulae can enrich its genetic data and lay a foundation for genetic quality control and gene mapping.Methods Microsatellite loci were screened based on the genome sequence of Apodemus peninsulae,and microsatellite primers were identified.The genetic diversity of the population was analyzed by multiplex PCR.Results Thirty microsatellite markers were successfully developed and evaluated using 60 samples of Apodemus peninsulae.A total of 152 alleles were detected,with an average of 5.067 alleles per locus.The average observed heterozygosity was 0.592.The average Shannon index was 1.265.The average polymorphism information content was 0.598.Conclusions Based on the microsatellite loci developed in this study,the genetic diversity of Apodemus peninsulae can be effectively analyzed,laying a foundation for establishing genetic quality standards and detection method.
6.Background, design, and preliminary implementation of China prospective multicenter birth cohort
Si ZHOU ; Liping GUAN ; Hanbo ZHANG ; Wenzhi YANG ; Qiaoling GENG ; Niya ZHOU ; Wenrui ZHAO ; Jia LI ; Zhiguang ZHAO ; Xi PU ; Dan ZHENG ; Hua JIN ; Fei HOU ; Jie GAO ; Wendi WANG ; Xiaohua WANG ; Aiju LIU ; Luming SUN ; Jing YI ; Zhang MAO ; Zhixu QIU ; Shuzhen WU ; Dongqun HUANG ; Xiaohang CHEN ; Fengxiang WEI ; Lianshuai ZHENG ; Xiao YANG ; Jianguo ZHANG ; Zhongjun LI ; Qingsong LIU ; Leilei WANG ; Lijian ZHAO ; Hongbo QI
Chinese Journal of Perinatal Medicine 2024;27(9):750-755
China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.
7.Clinical effect of upper eyelid lifting combined with orbicularis oculi muscle treatment by subbrow incision for upper eyelid skin relaxation
Yong DONG ; Wenzhi LI ; Huang LIN ; Xinliang CHEN
Chinese Journal of Medical Aesthetics and Cosmetology 2024;30(3):282-285
Objective:To explore the application effect of eyebrow lift combined with periorbital muscle manipulatation in the treatment of upper eyelid skin relaxation.Methods:From February 2017 to June 2022, a total of 52 female patients with upper eyelid skin laxity aged 38-64 (43.2±5.0) years, admitted to the Department of Plastic Surgery and Laser Medicine, Beijing Anzhen Hospital were selected for treatment in eyebrow lift with sub-brow excision, removed excess skin and orbicularis oculi muscle, and cut off part of periorbital muscle, and the orbicularis orbicularis muscle at the lower edge of the incision was suspend and fixed to the periosteum of supraorbital margin.Results:After following up from 6 months to 1 year after surgery, the upper eyelid slack and crow′s feet of 52 patients were improved significantly, no obvious downward movement appeared in the eyebrows, and the surgical effect was satisfied.Conclusions:The treatment of upper eyelid skin relaxation in eyebrow lift combined with periorbital muscle manipulatation can significantly improve the upper eyelid slack and crow′s feet, and it is worthy of clinical application.
8.Design and application of "1+3" management module for medical high-value consumables in Operation Room
Junhua ZHANG ; Ming XIAO ; Wenzhi CAI ; Wei LUO ; Lingwu CHEN ; Hong WANG ; Zhendong PEI ; Junyan YAO ; Juan XIAO
Chinese Journal of Modern Nursing 2024;30(13):1720-1723
Objective:To establish the "1+3" management module of high-value consumables in Operation Room and verify its application, so as to provide new ideas for cost management of consumables in Operation Room.Methods:The Operating Room team of Shenzhen Hospital of Southern Medical University designed a "1+3" management module in 2022, where "1" referred to the management process of high-value consumables in Operation Room, and "3" referred to the precise management of consumables in Operation Room warehouse, the management of closed-loop use of Operation Room consumables and adverse event management of consumables. Surgeries using high-value consumables in the Thoracic Surgery Department, Gastrointestinal Surgery Department, and Urology Department of the hospital were selected as the research objects. The surgeries using conventional consumables from January to June 2022 were set as the control group, and the surgeries implementing the "1+3" management module from July to December 2022 were set as the observation group. The number of consumables received by the itinerant nurses before the operation and the number of high-value consumables returned after the operation were compared between the two groups. And the number of missed and error charges for high-value consumables in the two groups were counted and compared.Results:The number of consumables received before operation in the control group was higher than that in the observation group, and the difference was statistically significant ( P<0.05). The number of high-value consumables returned in the observation group was less than that in the control group, and the difference was statistically significant ( P<0.01). The proportion of missed charges for consumables in the observation group was lower than that in the control group, and the difference was statistically significant ( P<0.01), but there was no statistically significant difference in the proportion of incorrect charges between the two groups ( P>0.05) . Conclusions:The "1+3" management module for high-value consumables in Operation Room makes the process of receiving, returning, and charging high-value consumables clear, with traceable data, achieving refined management of high-value consumables in Operation Room, reducing the number of high-value consumables returned to the warehouse and reducing the proportion of missed consumables, which is conducive to effective cost control in Operation Room.
9.Expression and clinical significance of interleukin-31 in plasma from patients with pulmonary arterial hypertension
Zhi ZHAN ; Xiaochun ZHANG ; Shiqiang HOU ; Lihua GUAN ; Dandan CHEN ; Wenzhi PAN ; Daxin ZHOU
Chinese Journal of Clinical Medicine 2024;31(3):394-401
Objective To investigate the plasma level of interleukin-31(IL-31)in patients with pulmonary arterial hypertension(PAH)and its clinical relevance.Methods The patients who were diagnosed as PAH in Zhongshan Hospital,Fudan University from January 1,2021 to December 30,2023(PAH group)and the healthy people in the same period(control group)were selected.The clinical data and follow-up records were collected.Plasma levels of IL-31,IL-1β,IL-6,IL-10,IL-12p70,monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α)and transforming growth factor-β1(TGF-β1)were detected by enzyme-linked immunosorbent assay(ELISA).Pearson correlation test was used to evaluate the correlations between IL-31 and right cardiac catheterization parameters,echocardiography parameters and blood indices in patients with PAH.Cox proportional hazard model was used to analyze the prognostic factors of patients in PAH group.Results A total of 50 patients with PAH and 22 healthy controls were included.There was no significant difference in age,gender,body mass index and left ventricular ejection fraction between the two groups.Compared with the control group,the plasma level of IL-31 in the PAH group was significantly higher(168.82[149.14,177.26]pg/mL vs 152.76[145.58,159.41]pg/mL,P=0.001).Pearson correlation test showed that the plasma level of IL-31 in PAH patient was positively correlated with mean pulmonary artery pressure(r=0.652,P<0.001)and pulmonary vascular resistance(r=0.651,P<0.001),but was negatively correlated with tricuspid annular plane systolic excursion(r=-0.496,P<0.001).Cox proportional hazard model showed that higher plasma level of IL-31 was an independent predictor of readmission for heart failure/all-cause mortality in patients with PAH(HR=1.130,95%CI 1.052-1.214,P=0.001).Conclusions Plasma level of IL-31 may be significantly increased in patients with PAH and be positively correlated with the severity of PAH,and elevated level of IL-31 is predictive of poor prognosis in PAH patients.
10.A nationwide multicenter prospective study on the perioperative impact of closure of mesen-teric fissure in laparoscopic right hemicolectomy
Gang LIU ; Weimin XU ; Da LI ; Lei QIAO ; Jieqing YUAN ; Dewei ZHANG ; Yan LIU ; Shuai GUO ; Xu ZHANG ; Wenzhi LIU ; Yingfei WANG ; Hang LU ; Xiaowei ZHANG ; Xin CHEN ; Zhaohui XU ; Xingyang LUO ; Ge LIU ; Cheng ZHANG ; Jianping ZHOU
Chinese Journal of Digestive Surgery 2024;23(6):812-818
Objective:To investigate the perioperative impact of closure of mesenteric fissure in laparoscopic right hemicolectomy.Methods:The prospective randomized controlled trial was conducted. The clinical data of 320 patients who underwent laparoscopic right hemicolectomy in 11 medical centers, including The First Affiliated Hospital of China Medical University et al, from November 2022 to August 2023 were selected. Based on block randomization, patients were alloca-ted into the mesenteric fissure non-closure group and the mesenteric fissure closure group. Observa-tion indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postopera-tive conditions. Measurement data with skewed distribution were represented as M( Q1, Q3) and com-parison between groups was conducted using the Mann-Whitney U test. Count data were represen-ted as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher's exact probability. Comparison of ordinal data was conducted using the rank sum test. Comparison of visual analog scores was analyzed using generalized estimating equations. Results:(1) Grouping of the enrolled patients. A total of 320 patients with colon cancer were screened for eligibility, including 156 males and 164 females, aged 68(59,73)years. All the 320 patients were allocated into the mesenteric fissure non-closure group with 164 cases and the mesenteric fissure closure group with 156 cases. There was no significant difference in the age, body mass index, American Society of Anesthesiologist score, maximum tumor diameter, anastomosis location, anastomosis method, surgical approach, range of lymph node dissection, tumor staging between the two groups ( P>0.05) and there was a significant difference in the sex between them ( P<0.05). (2) Intraoperative conditions. There was no significant difference between the mesenteric fissure closure group and the mesenteric fissure non-closure group in the volume of intraoperative blood loss, operation time, conversion to laparotomy, intraoperative complication ( P>0.05). Three patients in the mesenteric fissure non-closure group were converted to laparotomy. One patient in the mesenteric fissure closure group was converted to laparotomy, and 2 cases with intraoperative complication were mesenteric hematoma. (3) Postoperative conditions. There was no significant difference between the mesenteric fissure non-closure group and the mesenteric fissure closure group in the overall postoperative complications ( χ2=0.28, P>0.05). There was no significant difference in the occurrence of postoperative intestinal obstruction, abdominal distension, ascites, pleural effusion, gastric paralysis, anastomotic bleeding, anastomotic leakage, or surgical wound infection between the two groups ( P>0.05). There was no significant difference between the two groups in the reoperation, postoperative gastric tube replacement. There was no significant differ-ence in time to postoperative first flatus, time to postoperative initial liquid food intake, time to post-operative resumption of bowel movements, duration of postoperative hospital stay, total hospital expenses between the two groups ( Z=-0.01, 0.43, 1.04, -0.54, -0.36, P>0.05). One patient in the mesenteric fissure non-closure group received reoperation. No perioperative internal hernia or death occurred in either group. The visual analog score decreased with time in both groups. There was no significant difference in the visual analog score between the mesenteric fissure closure group and the mesenteric fissure non-closure group [ β=-0.20(-0.53,0.13), P>0.05]. Conclusion:Compared with closure of mesenteric fissure, non-closure of mesenteric fissure during laparoscopic right hemi-colectomy dose not increase perioperative complications or postoperative management risk.

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