1.Mechanism of action of sex hormones in regulating T cell-mediated autoimmune hepatitis: A study based on the phenomenon of female bias
Haiqiang WANG ; Dasha SUN ; Han WANG ; Jiahua TIAN ; Xinyue CUI ; Ming LI
Journal of Clinical Hepatology 2025;41(4):742-747
Autoimmune hepatitis (AIH) is an autoimmune disease characterized by liver parenchymal destruction and chronic fibrosis, and it is often mediated by T cells. The pathogenesis of AIH involves multiple factors, including sex, region, environmental factors, and genetic susceptibility. A notable predisposition is observed in female individuals, and the incidence rate of AIH in female individuals is significantly higher than that in male individuals. This sex difference is associated with various factors, and sex hormones may be an important cause of the female predominance of AIH, although the specific mechanisms remain unclear. An in-depth understanding of the mechanism of action of sex hormones in the pathogenesis of AIH will help to better understand the pathogenesis of the disease and may provide important clues for developing future treatment methods and prevention strategies. This article reviews the mechanism of action of estrogen and androgen in regulating the pathogenesis of AIH by regulating T cells, in order to provide new ideas and directions for further exploring the potential role of sex hormones in the etiology of autoimmune diseases.
2.The Mechanism of Action of Helicobacter pylori Infection in Inducing Mitochondrial Dysfunction
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1555-1562
3.E2 signaling in myofibers promots macrophage efferocytosis in mouse skeletal muscles with cardiotoxin-induced acute injury
Qihui CAI ; Haiqiang LAN ; Bojun XIAN ; Lian LIU ; Nan WANG ; Xiaolei HUANG ; Xiaolu NIU ; Xinyu HU ; Chen LI ; Junyi XIE ; Zhaohong LIAO
Journal of Southern Medical University 2024;44(11):2192-2200
Objective To investigate the effect of E2 signaling in myofibers on muscular macrophage efferocytosis in mice with cardiotoxin-induced acute skeletal muscle injury.Methods Female wild-type C57BL/6 mice with and without ovariectomy and male C57BL/6 mice were given a CTX injection into the anterior tibial muscle to induce acute muscle injury,followed by intramuscular injection of β-estradiol(E2)or 4-hydroxytamoxifen(4-OHT).The changes in serum E2 of the mice were detected using ELISA,and the number,phenotypes,and efferocytosis of the macrophages in the inflammatory exudates and myofiber regeneration and repair were evaluated using immunofluorescence staining and flow cytometry.C2C12 cells were induced to differentiate into mature myotubes,which were treated with IFN-γ for 24 before treatment with β-Estradiol or 4-OHT.The treated myotubes were co-cultured with mouse peritoneal macrophages in a 1:2 ratio,followed by addition of PKH67-labeled apoptotic mouse mononuclear spleen cells induced by UV irradiation,and macrophage efferocytosis was observed using immunofluorescence staining and flow cytometry.Results Compared with the control mice,the female mice with ovariectomy showed significantly increased mononuclear macrophages in the inflammatory exudates,with increased M1 cell percentage,reduced M2 cell percentage and macrophage efferocytosis in the injured muscle,and obviously delayed myofiber regeneration and repair.In the cell co-culture systems,treatment of the myotubes with β-estradiol significantly increased the number and proportion of M2 macrophages and macrophage efferocytosis,while 4-OHT treatment resulted in the opposite changes.Conclusion In injured mouse skeletal muscles,myofiber E2 signaling promotes M1 to M2 transition to increase macrophage efferocytosis,thereby relieving inflammation and promoting muscle regeneration and repair.
4.E2 signaling in myofibers promots macrophage efferocytosis in mouse skeletal muscles with cardiotoxin-induced acute injury
Qihui CAI ; Haiqiang LAN ; Bojun XIAN ; Lian LIU ; Nan WANG ; Xiaolei HUANG ; Xiaolu NIU ; Xinyu HU ; Chen LI ; Junyi XIE ; Zhaohong LIAO
Journal of Southern Medical University 2024;44(11):2192-2200
Objective To investigate the effect of E2 signaling in myofibers on muscular macrophage efferocytosis in mice with cardiotoxin-induced acute skeletal muscle injury.Methods Female wild-type C57BL/6 mice with and without ovariectomy and male C57BL/6 mice were given a CTX injection into the anterior tibial muscle to induce acute muscle injury,followed by intramuscular injection of β-estradiol(E2)or 4-hydroxytamoxifen(4-OHT).The changes in serum E2 of the mice were detected using ELISA,and the number,phenotypes,and efferocytosis of the macrophages in the inflammatory exudates and myofiber regeneration and repair were evaluated using immunofluorescence staining and flow cytometry.C2C12 cells were induced to differentiate into mature myotubes,which were treated with IFN-γ for 24 before treatment with β-Estradiol or 4-OHT.The treated myotubes were co-cultured with mouse peritoneal macrophages in a 1:2 ratio,followed by addition of PKH67-labeled apoptotic mouse mononuclear spleen cells induced by UV irradiation,and macrophage efferocytosis was observed using immunofluorescence staining and flow cytometry.Results Compared with the control mice,the female mice with ovariectomy showed significantly increased mononuclear macrophages in the inflammatory exudates,with increased M1 cell percentage,reduced M2 cell percentage and macrophage efferocytosis in the injured muscle,and obviously delayed myofiber regeneration and repair.In the cell co-culture systems,treatment of the myotubes with β-estradiol significantly increased the number and proportion of M2 macrophages and macrophage efferocytosis,while 4-OHT treatment resulted in the opposite changes.Conclusion In injured mouse skeletal muscles,myofiber E2 signaling promotes M1 to M2 transition to increase macrophage efferocytosis,thereby relieving inflammation and promoting muscle regeneration and repair.
5.OCT and IVUS evaluating stent apposition and endothelialization after FD implantation in aneurysm animal models
Ji MA ; Shuhai LONG ; Jie YANG ; Zhen LI ; Haiqiang SANG ; Yi TANG ; Yuncai RAN ; Yong ZHANG ; Baohong WEN ; Shanshan XIE ; Ke CHEN ; Enjie LIU ; Xinwei HAN ; Tengfei LI
Chinese Journal of Neuromedicine 2024;23(3):256-262
Objective:To investigate the application value of optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in evaluating flow diverter (FD) apposition and endothelialization in aneurysm animal models, and analyze the effect of incomplete stent apposition (ISA) on aneurysm lumen healing and stent endothelialization.Methods:Lateral common carotid artery aneurysm models in swines were established by surgical method and then FD was implanted. Immediately after surgery, OCT and IVUS were used to evaluate the locations and degrees of ISA, and difference between these 2 methods in evaluating FD apposition was compared. DSA was performed at 12 weeks after surgery to evaluate the aneurysm occlusion (Kamran grading) and stent patency. OCT and IVUS were used again to observe the stent endothelial situation; by comparing with histopathologic results, effect of ISA on aneurysm healing and stent endothelialization was analyzed.Results:Lateral common carotid artery aneurysm models in 6 swines were established, and 6 Tubridge FDs were successfully implanted. Compared with IVUS (3 stents, 4 locus), OCT could detect more ISA (6 stents, 14 locus); and the vascular diameter change area (7 locus), aneurysm neck area (4 locus) and the head and tail of FD (3 locus) were the main sites of FD malapposition; average distance between stent wire and vessel wall was (560.14±101.48) μm. At 12 weeks after surgery, DSA showed that 1 patient had a little residual contrast agent at the aneurysm neck (Kamran grading 3), and the remaining 5 had complete aneurysm occlusion (Kamran grading 4). One FD had moderate lumen stenosis, and the other 5 FDs had lumen patency. OCT indicated mostly disappeared acute ISA; ISA proportion decreased to 21.4 % (3/14), including 2 in the aneurysm neck and 1 in the partial stent. Histopathological results showed bare stent woven silk, without obvious endothelial coverage; in one FD with luminal stenosis, intimal hyperplasia was mainly composed of vascular smooth muscle cells.Conclusion:In carotid artery aneurysm model with FD implantation, OCT can detect more ISA than IVUS; most acute ISA have good outcome at 12 th week of follow-up, while severe ISA can cause delayed FD endothelialization and delayed aneurysm occlusion.
6.Clinical effect of the modified pharyngeal flap of bilateral muscular rings in the treatment of moderate and severe velopharyngeal insufficiency
Simo WU ; Bing SHI ; Zhihe ZHAO ; Junrui ZHANG ; Haiqiang LI
Chinese Journal of Stomatology 2024;59(6):617-621
To introduce the modified pharyngeal flap of bilateral muscular rings (BMR), and to discuss the clinical effect of this operation in the correction of moderate and severe velopharyngeal insufficiency. The clinical data of 18 patients who underwent BMR surgery in the Department of Craniofacial Plastic and Aesthetic Surgery, School of Stomatology, The Fourth Military Medical University from May 2019 to July 2021 were retrospectively analyzed. There were 10 males and 8 females, with a median age of 8.5 years (aged from 5 to 34 years). The patients were diagnosed preoperatively with moderate to severe velopharyngeal insufficiency (velopharyngeal closure ratio<0.7). The results of nasopharyngoscopy and speech assessment were compared and analyzed before operation and at the follow-up 6 months after the operation to evaluate the changes in velopharyngeal function and speech. Eighteen patients underwent BMR, 4 patients had snoring (the symptom disappeared after a few weeks in 3 cases), and 2 patients had local erosion of the wound, which delayed healing. Postoperative nasopharyngoscopy showed that all patients achieved comparatively complete velopharyngeal closure, some patients got enhanced lateral pharyngeal wall motility, and all patients got active motility of posterior pharyngeal wall flap. The postoperative speech assessment was significantly improved compared with that before the operation. The preoperative median score was 9 (range 7-12), and the postoperative median score was 2 (range 0-4). The statistical analysis was performed by paired non-parametric Wilcoxon signed rank test, and the difference was statistically significant ( P<0.001). BMR is a reliable method for the treatment of moderate and severe velopharyngeal insufficiency. This technique can achieve functional contraction of the full circumference of the ventilator while preserving the obstructive effect of the posterior pharyngeal wall flap, which is helpful to balance nasal ventilation and velopharyngeal closure and improve the velopharyngeal function of patients.
7.Association between diabetes prevalence and mortality risk in the elderly aged 60 years and above in Liaoning Province, 2017-2019
Yuanmeng TIAN ; Li JING ; Han YAN ; Boqiang ZHANG ; Haiqiang JIANG ; Shuang LI ; Jiabao SONG ; Shuang LIU ; Liying XING
Chinese Journal of Epidemiology 2024;45(7):941-946
Objective:To investigate the prevalence of diabetes in the elderly aged ≥60 years in Liaoning Province from 2017 to 2019 and analyze the impact of blood glucose control on all-cause mortality and cardiovascular disease (CVD) mortality.Methods:A survey was conducted in the elderly aged ≥60 years in Liaoning from 2017 to 2019 to collect the information about the prevalence of diabetes and other chronic diseases in the diabetes patients. The mortality of the enrolled subjects was investigated in September 2023. Cox proportional hazards regression models were used to estimate the association between blood glucose control in the elderly with diabetes and the risks of all-cause mortality and CVD mortality.Results:The crude prevalence of diabetes in the elderly aged ≥60 years was 20.2% (2 014/9 958) in Liaoning from 2017 to 2019, and the standardized prevalence rate was 19.9%. The prevalence rates of hypertension, dyslipidemia, and overweight/obesity in the diabetes patients were 77.0%, 51.7%, and 67.5% respectively. The median follow-up time was 5.5 years, and the all-cause mortality and CVD mortality rates in the diabetes patients were 244.3/10 000 person-years and 142.9/10 000 person-years, respectively. The results of the Cox proportional hazards regression model analysis showed that compared with non-diabetic individuals, diabetes patients had an increased risk of all-cause mortality by 1.68 times [hazard ratio ( HR)=1.68, 95% CI: 1.44-1.94] and an increased risk of CVD mortality by 1.56 times ( HR=1.56, 95% CI: 1.29-1.89). The differences in risks of all-cause mortality and CVD mortality between the diabetes patients with normal fasting blood glucose and glycated hemoglobin levels and people without diabetes were not significant (all P>0.05). The failure to meet either the FPG or HbA1c target increased the risk of all-cause mortality (all P<0.05). For individuals who failed to meet the HbA1c target, there was an increased risk of CVD mortality (all P<0.05). Conclusions:The comorbidity rate of chronic diseases was higher in the elderly with diabetes than in the elderly without diabetes in Liaoning. Elderly diabetes patients can benefit from good blood glucose control.
8.Construction and application of an injectable cartilage graft
Chaoqun MA ; Haiqiang LI ; Wei WU
Journal of Practical Stomatology 2024;40(1):20-25
Objective:To explore a set of procedures for the effictive granulation of cartilage,and to construct injectable cartilage graft with platelet-rich gel(PRG),and to evaluate its effects in nude mice models.Methods:The costal cartilage of adult male rab-bits was cut into pieces and placed in a mortar for 30-60 s freezing in liquid nitrogen and grinding for a short time to obtain granular cartilage.Blood was collected from the middle ear artery and PRG was prepared by double centrifugation.Granular cartilage and the mixture of granular cartilage and PRG were injected subcutaneously in nude mice of control group(n=5)and experimental group(n=5)respectively.8 weeks after injection,the gross morphology observation and histological examination were pertormed.The nasal dor-sum augmentation model of nude mice was established in the experimental group.Results:The cartilage particles were in the size of 10-500 pm in diameter after frozen grinding,and injection could be realized.In vitro culture showed that the cell survival rate of granular cartilage reached to 80%.In vivo test showed that the sample morphology of the control group was insignificant,and the sur-face was grainy.That of the experimental group was well maintained,and the surface was smooth with obvious capillaries.The sam-ples of experimental group achieved significant augmentation in the nude mouse model of nasal dorsum augmentation.Conclusion:Freeze-milling technology can achieve efficient granulation of cartilage,and the graft constructed with PRG gel is suitable for maxillo-facial cartilage transplantation repair.
9.Mechanism of Changyuning on PI3K/AKT Signaling Pathway in Ulcerative Colitis Rats
Haiqiang WANG ; Meng ZHANG ; Li XIONG ; Chenxi MA ; Yao WANG ; Lihong ZHENG
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(11):3736-3743
Objective To investigate the effect of Changyuning prescription on PTEN,TLR2,Caspase-3,Caspase-9 in phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway in colon tissue of 2,4,6-trinitrobenzenesulfonic acid(TNBS)-induced ulcerative colitis(UC)rats.Methods After adaptive feeding for 7 days,70 SPF rats were divided into blank group of 10 and modeling group of 60.The rats in the modeling group were given TNBS/ethanol solution enema to induce UC model.The rats that successfully bulit the model were randomly divided into model group,mesalazine group,Changyuning high-dose,medium-dose and low-dose groups,and Changyuning high-dose,medium-dose and low-dose groups,respectively,and the equivalent amount of crude drug was 4 g·mL-1,2 g·mL-1,1 g·mL-1 of Changyuning prescription solution 10 mL·kg-1,the mesalamine group was given 10 mL·kg-1 of mesalamine suspension equivalent to 0.2 g·kg-1 crude drug,the blank control group and model group were given an equal volume of 10 mL·kg-1 of normal saline was given by gavage.The rats in each group were given intragastric administration once a day for 14 consecutive days.Rats were sacrificed after the last administration.Disease activity index was evaluated;colon changes were observed by HE staining;colon tissue damage index was evaluated;The expression of PI3K,AKT,PTEN,TLR2,Caspase-3,and Caspase-9 proteins was detected by Western Blotting in colon tissue.Results Compared with the blank group,the protein expression levels of PI3K,AKT,Caspase-3,Caspase-9 and TLR2 in the model group were increased(P<0.05),and the protein expression level of PTEN was decreased(P<0.05).Compared with the model group,the expression levels of PI3K,AKT,Caspase-3,Caspase-9 and TLR2 proteins in the Changyuning high-dose group were significantly decreased(P<0.05),and the protein expression levels of PTEN were significantly increased(P<0.05);The levels of PI3K,AKT and Caspase-3 in the salazine group and Changyuning medium dose were decreased(P<0.05),the expression level of PTEN protein was increased(P<0.05),and there was no statistical significance in the expression of Caspase-9;There was no statistical significance in the expression of each protein between the Changyuning low-dose group and the model group.Conclusion Changyuning recipe has a significant effect on the treatment of UC,and its mechanism may be related to the regulation of PI3K/AKT signaling pathway and its related proteins PTEN,TLR2,Caspase-3,and Caspase-9,which can effectively relieve the symptoms of UC rats and reduce colon pathological damage.
10.Prognostic value of pretreatment systemic immune-inflammation index and lactate dydrogenasein nasopharyngeal carcinoma
Fengge ZHOU ; Liting LIU ; Xiaodong HUANG ; Shiran SUN ; Xuesong CHEN ; Qiuyan CHEN ; Linquan TANG ; Haiqiang MAI ; Kai WANG ; Yuan QU ; Runye WU ; Ye ZHANG ; Qingfeng LIU ; Jianghu ZHANG ; Jingwei LUO ; Jianping XIAO ; Li GAO ; Guozhen XU ; Jingbo WANG ; Junlin YI
Chinese Journal of Oncology 2022;44(8):842-850
Objective:To evaluate the prognostic value of pretreatment systemic immune-inflammation index (SII) and lactate dehydrogenase (LDH) in non-metastatic nasopharyngeal carcinoma (NPC).Methods:We retrospectively collected the data of 839 patients with non-metastatic NPC from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Sun Yat-sen University Cancer Center between January 2007 and October 2015. All patients received intensity modulated radiation based treatment. Optimal cutoff value of SII and LDH were determined by X-title software. The association between SII, LDH and clinical prognosis of non-metastatic NPC patients were analyzed. Kaplan-Meier method was used for survival analysis, and Log rank test was used for comparison of survival rates between groups. Propensity score matching (PSM) analysis was carried out to minimize the effects of confounding factors. The risk stratification model of prognosis by combining N stage, SII and LDH was constructed to compare the prognosis of patients in high risk group, middle risk group and low risk group, and the receiver operating characteristic (ROC) curve analysis was used to evaluate its prognostic value.Results:The optimal cutoff value of SII is 447.2×10 9/L for predicting the 5-year overall survival (OS) of NPC patients, and the best cutoff value of LDH is 198.9 U/L. The proportion of patients with stage T3-4 and stage III-IVB in high SII group was higher than that in low SII group ( P<0.001). Multivariate Cox regression analysis showed that N stage, SII and LDH were independent factors of OS, progression-free survival (PFS) and distant metastasis-free survival (DMFS) of NPC patients (N stage, HR=1.705, 95% CI: 1.247-2.332; HR=1.755, 95% CI: 1.342-2.295; HR=2.161, 95% CI: 1.515-3.082. SII, HR=1.525, 95% CI: 1.097-2.119; HR=1.518, 95% CI: 1.150-2.004; HR=1.837, 95% CI: 1.272-2.653. LDH, HR=2.041, 95% CI: 1.403-2.968; HR=1.725, 95% CI: 1.233-2.414; HR=2.492, 95% CI: 1.690-3.672, respectively). After PSM, SII was still an independent prognostic factor of OS, PFS and DMFS in NPC patients ( HR=1.52, 95% CI: 1.09-2.12; HR=1.52, 95% CI: 1.15-2.00; HR=1.82, 95% CI: 1.26-2.63, respectively). Combined with N 2-3 stage, SII (>447.2×10 9/L), and LDH (>198.9 U/L), patients were divided into high-(3 risk factors), intermediate- (2 risk factors) and low-risk (0-1 risk factors) groups. The 5-year OS rates of patients in low-, intermediate- and high-risk groups were 86.1%, 79.8% and 41.2% respectively, the 5-year PFS rates were 80.7%, 70.2% and 33.9% respectively, and the 5-year DMFS rates were 88.9%, 79.2% and 47.5% respectively. There were significant differences in OS, PFS and DMFS among these three groups ( P<0.001). Distant metastasis was the main failure pattern in low-, intermediate- and high-risk groups, and the highest rate of distant metastasis was 83.3% (15/31) in high-risk group. ROC curve of the risk stratification model for predicting 5-year OS of NPC patients is 0.610, which is higher than TNM stage (0.609), SII (0.574) and LDH (0.558). Conclusions:Pretreatment SII and LDH are significantly correlated with the prognosis of patients with non-metastatic NPC. The combination of SII, LDH and N stage can stratify the prognostic risk of NPC patients. The risk stratification model can enhance the accuracy of prognosis.

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