1.Regulation of Rat Intervertebral Disc Annulus Fibrosus Cell Proliferation and Apoptosis by Yaoshu Zhuyu Fang via miR-17-5P/MDM2/p53 Pathway
Haitao JIANG ; Hantao YUAN ; Wenting HUANG ; Rongrong YANG ; Xiaochun CHEN ; Baoqing YU ; Sibo LI
Laboratory Animal and Comparative Medicine 2026;46(1):55-65
ObjectiveTo investigate the effect of Yaoshu Zhuyu Fang on the regulation of the microRNA-17-5P (miR-17-5P)/murine double minute 2 (MDM2)/p53 axis in the proliferation and apoptosis of rat intervertebral disc annulus fibrosus cells, and its potential molecular mechanism. MethodsIntervertebral disc annulus fibrosus tissues were obtained from 8-week-old SPF-grade male SD rats, and annulus fibrosus cells were isolated and obtained by enzyme digestion and mechanical dispersion. Annulus fibrosus cells were divided into 6 groups: Group C was the blank control group, in which annulus fibrosus cells were not treated with interleukin-1β (IL-1β) but were cultured in RPMI 1640 complete medium. Group β was the degeneration model group constructed by treating annulus fibrosus cells with 10 ng/mL IL-1β for 24 h. Group β+B was the IL-1β + blank serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% blank serum for 24 h. Group β+W was the IL-1β + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. Group β+I was the IL-1β + miR-17-5P inhibitor group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor. Group β+I+W was the IL-1β + miR-17-5P inhibitor + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor, and finally treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. CCK-8 assay was used to detect cell survival rate. Flow cytometry was used to detect cell apoptosis. Real-time quantitative PCR was used to detect the expression levels of miR-17-5P, MDM2 mRNA, and p53 mRNA in cells. Western blotting was used to detect the protein expression levels of MDM2 and p53 in cells. Dual-luciferase reporter system was used to analyze the targeting relationship between miR-17-5P and MDM2. ResultsCompared with Group C, Group β showed a significant decrease in cell survival rate (P<0.001), a significant increase in cell apoptosis rate (P<0.001), significantly increased expression of miR-17-5P, p53 mRNA, and p53 protein (P<0.001), and significantly decreased expression of MDM2 mRNA and protein (P<0.001). Compared with Group β, Group β+W, Group β+I, and Group β+I+W showed significantly increased cell survival rate, significantly decreased apoptosis rate, significantly decreased expression of miR-17-5P, p53 mRNA, and p53 protein, and significantly increased expression of MDM2 mRNA and protein (P<0.001). Moreover, changes in the above indicators were greater in Group β+I+W (P<0.001). Circular RNA Interactome predicted that miR-17-5P had specific binding sites with the 3' untranslated region (3'UTR) of MDM2. Transfection of miR-17-5P mimic significantly reduced the luciferase expression level of co-transfected luciferase reporter plasmid containing wild-type MDM2 3'UTR (P<0.05), but had no significant effect on luciferase expression in cells co-transfected with luciferase reporter plasmid containing mutant MDM2 3'UTR (P>0.05). ConclusionYaoshu Zhuyu Fang down-regulates the expression of miR-17-5P, promotes the synthesis of MDM2 protein, thereby down-regulates p53, promotes proliferation, and inhibits the apoptosis of rat intervertebral disc annulus fibrosus cells.
2.Chinese expert consensus on salvage esophagectomy for esophageal cancer after definitive chemoradiotherapy
Zhaoxian LIN ; Yang HU ; Lei XIAN ; Yun LI ; Jinbo ZHAO ; Xiaobin HOU ; Shuangping ZHANG ; Sunkui KE ; Changying GUO ; Songping XIE ; Haitao WEI ; Yong LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(07):977-987
Definitive chemoradiotherapy (dCRT) has become a cornerstone in the treatment of locally advanced esophageal cancer; however, local control remains suboptimal, and persistent lesions or locoregional recurrences after treatment are not uncommon. For patients without distant metastases but with local failure, whether surgical intervention can still offer curative potential remains a major clinical dilemma. Salvage esophagectomy (SE) offers potential long-term survival for selected patients, but this procedure is performed in the context of severe fibrosis, impaired local blood supply, and obscured anatomical planes following chemoradiotherapy, resulting in significantly higher perioperative risk compared to primary esophagectomy. Consequently, controversies exist regarding patient selection, preoperative restaging, choice of surgical approach, extent of lymphadenectomy, gastrointestinal reconstruction, and perioperative management. In recent years, with the refinement of restaging modalities such as PET/CT, the accumulation of experience in high-volume centers, and emerging evidence from clinical studies, the clinical role of SE has gradually shifted from a "high-risk salvage measure" to a "selective curative strategy aimed at achieving long-term survival in carefully selected patients". Nevertheless, standardized guidelines for patient selection, technical approaches, and perioperative management are still lacking. Based on current evidence and clinical experience, experts organized by the Integrated Esophageal Cancer Committee of Chinese Anti-Cancer Association systematically reviewed key issues regarding SE, including its definition, indications, preoperative evaluation, choice of surgical approach, lymphadenectomy, gastrointestinal reconstruction, and perioperative management, and formulated a Chinese expert consensus. This consensus aims to provide guidance for standardized assessment, appropriate referral, individualized surgical decision-making, and optimized perioperative management of patients with locoregional failure after dCRT. Ultimately, this will increase the likelihood of R0 resection, reduce the risk of severe complications, and promote the safer, more judicious, and standardized implementation of SE in high-risk scenarios.
3.Epidemic characteristics and factors influencing mortality in HIV/HCV co-infected population in Heilongjiang Region
Journal of Public Health and Preventive Medicine 2025;36(1):101-104
Objective To investigate the epidemic characteristics and factors influencing mortality in human immunodeficiency virus (HIV) and hepatitis C virus (HCV)-coinfected patients in heilongjiang region. Methods The clinical data of 712 HIV-infected patients attending our hospital from January 2019 to December 2023 were analyzed retrospectively. The HCV infections were detected by ELISA, and epidemic characteristics of HIV/HCV co-infected patients were analyzed . Co-infected patients (n=116) were classified into survival group (n=90) and death group (n=26) according to the follow-up results, and risk factors for the mortality of HIV/HCV co-infected patients were identified. Results The prevalence of HIV/HCV co-infection was 16.29%, and the prevalence was the highest in 30-50 age group, accounting for 25.47%. There was no significant difference in co-infection rates by gender and marital status (P>0.05). The co-infection rate was the highest among farmers (26.85%) by occupation and among intravenous drug users (61.90%) by route of infection. No statistical difference was found in gender, marital status, and occupational status between survival group and death group (P>0.05), whereas statistical difference was found in age at diagnosis of HIV infection, route of infection, antiretroviral treatment, percentage of CD4+T lymphocytes, and interval between diagnosis and initiation of treatment between two groups (P<0.05). Multivariate Logistic regression analysis denoted that age at diagnosis of HIV infection (OR=1.827, 95% CI: 1.263-2.722), route of infection (OR=1.796, 95% CI: 1.248-2.503), antiretroviral treatment (OR=1.724, 95% CI: 1.202-2.367), percentage of CD4+T lymphocytes (OR=2.536, 95% CI: 1.776-3.739), and the time interval between diagnosis and initiation of treatment (OR=1.953, 95% CI: 1.431-2.952) were all associated with the risk of mortality in co-infected patients (P<0.05). Conclusion The overall prevalence of HIV/HCV co-infection is 16.29% in heilongjiang region . In order to reduce the mortality rate of superinfection , we should focus on patients who are ≥ 40 years old, intravenous drug use , no antiviral therapy , low CD4+ T lymphocyte levels for the first time , and have a long interval between diagnosis and initiation of treatment.
4.Effects of Xiaomudan Granules on PERK/eIF2α/ATF4 pathway and lipid metabolism in mice with nonalcoholic fatty liver
Haitao LIU ; Jingtao LI ; Longmei LI ; Qingrui YANG ; Xinzhu LI ; Yuyu LEI ; Zhiqiang JING
International Journal of Traditional Chinese Medicine 2025;47(7):932-937
Objective:To investigate the effects of Xiaomudan Granules on PERK/eIF2α/ATF4 pathway and lipid metabolism in NAFLD mice.Methods:Totally 60 mice were divided into a normal group of 10 mice and a high-fat diet group of 50 mice. The high-fat diet group was given a high-fat diet to establish a NAFLD mouse model. The high-fat feed group was divided into model group, metformin group, and Xiaomudan Granules low-, medium-, and high-dosage groups according to the random number table method. Xiaomudan Granules low-, medium-, and high-dosage groups were orally administered with concentrated Xiaomudan Granules at dosages of 11.7, 23.4, and 46.8 g/kg, respectively. The metformin group was orally administered with metformin solution at a dose of 0.2 g/kg, while the normal group and model group were orally administered with distilled water of equal volume once a day for 8 consecutive weeks. The liver oil red O staining of mice was observed in each group. The protein expressions of p-PERK, p-eIF2α, ATF4, C/EBP homologous protein (CHOP), CCAAT enhancer binding protein alpha (C/EBPα), C/EBPβ, and steroid regulatory element binding protein 2 (SREBP2) were detected by Western blot. Fluorescence quantitative PCR was used to detect the mRNA expressions of ATF4, CHOP, C/EBPα, C/EBPβ, and SREBP2.Results:The liver tissue structure and steatosis of mice were improved in Xiaomudan Granules groups. Compared with the model group, the expressions of p-PERK/PERK, ATF4, C/EBPα, C/EBPβ, and SREBP2 proteins decreased in Xiaomudan Granules groups and the metformin group ( P<0.01 or P<0.05). The expressions of p-eIF2α/eIF2α and CHOP proteins decreased in the Xiaomudan Granules medium- and high-dosage groups and the metformin group ( P<0.01); compared with the model group, the levels of ATF4, CHOP, C/EBPα, and C/EBPβ mRNA in Xiaomudan Granules groups and the metformin group decreased ( P<0.01), while the levels of SREBP2 mRNA in the Xiaomudan Granules medium- and high-dosage groups and the metformin group decreased ( P<0.01). Conclusion:Xiaomudan Granules may improve liver lipid metabolism and reduce liver fat deposition in NAFLD mice by regulating the PERK/eIF2α/ATF4 pathway.
5.Clinical Observation of Lingnan Fire Needle Therapy Combined with Conventional Western Medicine in the Treatment of Mild to Moderate Uterine Prolapse
Weiye FANG ; Huiping LI ; Haitao YANG
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(6):1413-1419
Objective To observe the clinical efficacy of Lingnan fire needle therapy combined with conventional western medicine in the treatment of mild to moderate uterine prolapse.Methods A total of 96 patients diagnosed with mild to moderate uterine prolapse in the outpatient and inpatient departments of Dongguan Humen Traditional Chinese Medicine Hospital from January 2023 to January 2024 were selected as the study subjects.The patients were randomly divided into an observation group and a control group using a random number table,with 48 cases in each group.Both groups received health education,and the control group received conventional western medicine treatment.The observation group received Lingnan fire needle therapy in addition to the control group's treatment.The treatment course consisted of 12 sessions,with one course completed.After treatment,the clinical efficacy of the two groups was evaluated.Changes in TCM syndrome scores,pelvic floor muscle strength,and ultrasound imaging characteristics were observed before and after treatment.The serum levels of osteopontin(OPN),connective tissue growth factor(CTGF),and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1(MMP-9/TIMP-1)were compared before and after treatment.The safety and incidence of adverse reactions in the two groups were evaluated.Results(1)The total effective rate in the observation group was 97.92%(47/48),while it was 77.08%(37/48)in the control group.The efficacy of the observation group was superior to that of the control group,with a statistically significant difference(P<0.05).(2)After treatment,the TCM syndrome scores and total scores in both groups significantly improved(P<0.05),and the observation group showed significantly better improvement in these scores compared to the control group,with a statistically significant difference(P<0.05).(3)After treatment,the pelvic floor muscle strength and ultrasound imaging characteristics in both groups significantly improved(P<0.05),and the observation group showed significantly better improvement in these aspects compared to the control group,with a statistically significant difference(P<0.05).(4)After treatment,the serum levels of OPN,CTGF,and MMP-9/TIMP-1 in both groups significantly improved(P<0.05),and the observation group showed significantly better improvement in these levels compared to the control group,with a statistically significant difference(P<0.05).(5)There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion Lingnan fire needle therapy combined with conventional western medicine can significantly improve symptoms and pelvic floor muscle strength in patients with mild to moderate uterine prolapse,with notable efficacy and high safety.The mechanism may be related to the regulation of OPN,CTGF,and MMP-9/TIMP-1 levels.
6.Biejiajian Pill Regulates Ferroptosis in Hepatocellular Carcinoma Cells via p62/Keap1/NRF2 Signaling Pathway:A Mechanism Study
Weiguang CHEN ; Chunyu HE ; Bin WEN ; Haitao SUN ; Xuemei YANG ; Weicong CHEN ; Yang LIU ; Binglian ZHONG ; Songqi HE
Journal of Sichuan University (Medical Sciences) 2025;56(1):51-58
Objective To investigate the mechanism by which Biejiajian Pill(BJJP)regulates ferroptosis in hepatocellular carcinoma(HCC)cells through the p62/Keap1/NRF2 pathway and to provide an experimental basis for its application in the prevention and treatment of HCC.Methods Huh7 HCC cells were divided into a normal control group,a BJJP drug serum group,an erastin(a ferroptosis inducer)group,a BJJP drug serum+erastin group,and BJJP drug serum+ferrostatin-1(Fer-1)(a ferroptosis inhibitor)group.BJJP drug serum was prepared with animals treated with BJJP and CCK-8 assay was performed to determine the optimal concentration and duration of BJJP intervention.The levels of intracellular iron(Fe),reduced glutathione(GSH),lipid peroxides(MDA),and reactive oxygen species(ROS)were measured.Western blot was performed to determine the expression levels of FTH1,GPX4,xCT,SLC40A1,Keapl,p62,and NRF2.JC-1 staining was performed to measure mitochondrial membrane potential,and cell immunofluorescence was performed to determine the expression of p62 and Keap1.Results According to the CCK-8 assay results,the cell inhibition rate was highest when BJJP was administered at a high dose of 2.2 g/kg(P<0.001).Furthermore,the inhibition rate of Huh7 cells was highest when Huh7 cells were treated with high-dose BJJP drug serum for 48 h.Therefore,the serum concentration of high-dose BJJP and 48 h were selected as the treatment dose and duration for the subsequent experiment.Compared with the control group,the BJJP drug serum group,the erastin group,and the BJJP drug serum+erastin group showed increased iron content,decreased GSH content,increased MDA levels,increased ROS aggregation,decreased FTH1,GPX4,xCT,SLC40A1,p62,and NRF2 contents,increased Keap1 content,and decreased mitochondrial membrane potential(P<0.05).Conclusion BJJP regulates ferroptosis in Huh7 HCC cells by inhibiting the p62/Keap1/NRF2 pathway,demonstrating potentials as a therapeutic agent for HCC.
7.The cultivation of empathy in clinical teaching of oral medicine
Zhen LI ; Haitao DONG ; Wen CAI ; Chunlan LI ; Youjia TANG ; Xiaowei ZHANG ; Wendong YANG
Basic & Clinical Medicine 2025;45(6):834-837
Empathy is a cornerstone in cultivating medical ethics.This article delves into the profound significance of empathy and underscores the importance of promoting it among medical students and practitioners.It also details methods for strengthening empathy and capacity building concerned in students through oral medicine instruction,with the goal of nurturing oral healthcare professionals who provide compassionate care.
8.Inpatients with oral and maxillofacial military training injuries:a retrospective analysis
Jianzhen SHE ; Haitao KONG ; Luying YANG ; Fan SHI ; Lei TIAN ; Liang KONG ; Bolei CAI
Military Medical Sciences 2025;49(1):22-26
Objective To analyze the characteristics of oral and maxillofacial injuries from military training and provide references for related prevention and treatment.Methods A retrospective analysis was conducted of the medical records of 111 patients with oral and maxillofacial military training injuries treated between 2014 and 2023.Results From 2014 to 2023,the number of hospitalized patients with maxillofacial military training injuries in the hospital trended upward.The top 3 training injuries in the spectrum of diseases were maxillofacial fractures(45.08%),maxillofacial space infections(28.83%),and temporomandibular joint injuries(18.92%).The average number of hospitalizations for all maxillofacial military training injuries was 1.33(1-4),and the median length of hospital stay was 8(5,12)days.The median hospitalization cost was 14 793.23(5236.18,24 255.25)yuan,and the improvement rate was 95.50%.Conclusion The number of patients hospitalized due to oral and maxillofacial military training injuries in this hospital is increasing year by year,and the injuries are mostly jaw fractures.Precautions should be taken to prevent maxillofacial training injuries.
9.Effect of preoperative pancreatic duct stent placement in enucleation of pancreatic tumor adjacent to the main pancreatic duct
Haotian YU ; Shubin ZHANG ; Jianhua LIU ; Jianzhang QIN ; Chengxu DU ; Xinda YANG ; Weihong ZHAO ; Haitao LYU
Chinese Journal of Hepatobiliary Surgery 2025;31(1):43-48
Objective:To study the effect of preoperative pancreatic duct stent placement in enucleation (EN) of pancreatic tumor adjacent to the main pancreatic duct (MPD).Methods:Clinical data of 56 patients with benign or borderline pancreatic tumor adjacent to the MPD undergoing EN in the Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University from January 2022 to September 2024 were retrospectively analyzed, including 25 males and 31 females, aged (32.0±5.5) years. Among the patients, 35 (62.5%) were solid pseudopapillary neoplasm, 15 (26.8%) were neuroendocrine tumor, and 6 (10.7%) were serous cystic tumor. According to whether the pancreatic duct stent was placed through encoscopic retrograde cholangiopancreatography preoperatively, patients were divided into the stent group ( n=20, observation group) and no-stent group ( n=36, control group). The operation time, intraoperative pancreatic duct injury, tumor enucleation time and blood loss, grade B/C pancreatic fistula and postoperative hospital stay were compared between the two groups. Results:All patients underwent EN successfully. The operation time in the observation group was shorter than that in the control group [150.0 (143.5, 159.0) vs 158.0 (150.0, 180.0) min, Z=-2.08, P=0.031], and the rate of intraoperative MPD injury in the observation group was lower than that in the control group [10.0% (2/20) vs 38.9% (14/36), χ2=5.26, P=0.022]. The tumor enucleation time and blood loss were comparable between the two groups (both P>0.05). The rate of postoperative grade B/C pancreatic fistula in the observation group was lower than that in the control group [15.0% (3/20) vs 41.7% (15/36), χ2=4.19, P=0.041], and the postoperative hospital stay was also shorter in the observation group [(7.9±1.6) vs (9.3±2.1) d, t=-2.57, P=0.014]. Conclusion:Under the premise of matured endoscopic operation, preoperative pancreatic duct stent placement through ERCP in the EN of pancreatic tumor adjacent to the MPD can protect the MPD during operation, reduce the occurrence of postoperative grade B/C pancreatic fistula, and shorten the postoperative hospital stay.
10.Aerobic exercise activates SLC7A11/GPx4 pathway to inhibit mitochondrial ferroptosis and prevent sarco-penia in aging mice
Haitao WANG ; Wenqian YANG ; Yuqian LIU
Chinese Journal of Rehabilitation Medicine 2025;40(4):501-507
Objective:To elucidate the role of solute carrier protein 7,family member 11(SLC7A11)/Glutathione peroxi-dase 4(glutathione peroxidase 4,GPx4)regulated ferroptosis pathway in the improvement of sarcopenia through aerobic exercise,and to identify a new target for the prevention and treatment of sarcopenia with exercise.Method:Twenty 52-week-old Specific pathogen Free(SPF)C57BL/6 male mice were randomly divided into the old control group(OC)and the old exercise group(OE).There were 10 mice in each group.Following one week of adaptive exercise,moderate-intensity exercise with incremental load was implemented as follows:14 m/min at 1-2 weeks,15 m/min at 3-4 weeks,16m/min at 5-10weeks,17m/min at 11-16weeks,60min/d,all with a slope of 0°.Gastrocnemius was harvested for ultrathin electron microscope sections.The levels of Glutathione(GSH),muscle glycogen and non-heme iron(non-heme iron)were measured by spectro-photometer.The serum ferritin(SF),mitochondrial 8-hydroxy-2 deoxyguanosine(8-OHdG)and 4-Hydroxynone-na(4-HNE)were measured by enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the expression of iron metabolism-related proteins,such as GPx4,SLC7A11,ferroportin 1(FPN1)and ferri-tin heavy chain 1(FTH1)in gastrocnemius muscle.Result:①Compared with OC,the wet weights of quadriceps femoris and gastrocnemius in OE were signifi-cantly increased(P<0.01).In the exercise group,mitochondrial cristae arranged neatly and densely,and the light and dark bands of myofilaments were clear.In the aged control group,the mitochondrial cristae of gas-trocnemius muscle were disrupted,vacuolated or pyknotic,showing typical features of ferroptosis.② The SF and the iron content of gastrocnemius muscle were decreased in OE(P<0.01).③ The levels of 4-HNE and 8-OHdG in gastrocnemius muscle of OE were significantly lower than those of OC(P<0.01).The GSH content in gastrocnemius of OE was significantly higher than that of OC(P<0.01).④ The expressions of SLC7A11,GPx4,FPN1 and FTH1 in gastrocnemius muscle of OE were significantly higher than those of OC(P<0.01).Conclusion:Moderate aerobic exercise can prevent age-related sarcopenia by activating the SLC7A11/GPx4 pathway and inhibiting mitochondrial ferroptosis.


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