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.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.
3.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.
4.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.
5.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.
6.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.
7.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.
8.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.
9.Effect of reperfusion injury following different ischemic duration on skeletal muscle in rats
Shengye ZHANG ; Linjie YANG ; Yunpeng LI ; Fudong HU ; Shengcun GUO ; Dong CHENG ; Yi TANG ; Ding YU ; Haiqiang SANG
Chinese Journal of Trauma 2022;38(2):172-181
Objective:To investigate effect of reperfusion injury following different ischemic duration on skeletal muscle in rats.Methods:A model of ischemia/reperfusion injury (IRI) was established by unilateral clamping femoral artery and additional application of tourniquet in skeletal muscle of hind limbs in 35 male Wsitar rats. According to different ischemia time, the animals were assigned to 2-hour ischemia and 24-hour reperfusion (I2R24 group), 2.5-hour ischemia and 24-hour reperfusion (I2.5R24 group), 3-hour ischemia and 24-hour reperfusion (I3R24 group), 4-hour ischemia and 24-hour reperfusion (I4R24 group) and sham group, with 7 rats per group. At the end of reperfusion, gastrocnemious tissues and plasma samples were collected and analyzed. The ratio of wet ∶ dry weight (W/D) was used to measure muscle edema. The assay of 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) was conducted to evaluate muscle viability. HE staining was executed to observe histopathological changes. Immunofluorescence staining was performed to assess the levels of C1q, C3b/c, tissue factor (TF), fibrinogen (FN), bradykinin receptor 1 (BR1), BR2, vascular cell adhesion molecule-1 (VCAM-1), E-selectin, fibrinogen-like protein-2 (FGL-2) and myeloperoxidase (MPO) in muscle tissues. ELISA method was used to determine the concentrations of interferonγ (IFN-γ), interleukin7 (IL-7), IL-18, macrophage inflammatory1α (MIP-1α) and monocyte chemotactic protein 1 (MCP-1) in plasma.Results:With prolongation of ischemia time and subsequent reperfusion, tissue edema became severe gradually. The ratio of W/D was 5.3±0.2, 6.1±0.3, 6.9±0.2, 7.6±0.3 in I2R24, I2.5R24, I3R24 and I4R24 groups, higher than that in sham group (4.5±0.1) (all P<0.01). Muscle viability got decreased gradually. Muscle viability was (62.4±3.5)%, (45.3±3.3)%, (35.4±3.4)%, (27.1±5.9)% in I2R24, I2.5R24, I3R24 and I4R24 groups, lower than that in sham group[(93.8±7.2)%](all P<0.01). Histopathological changes became aggravated gradually. The most severe group was I4R24 group, with the most severe myocyte injury, interstitial edema and extensive inflammatory infiltration, followed by I3R24, I2.5R24 and I2R24 groups in order. There was normal structure integrity and neatly arranged myocyte in sham group. Meanwhile, levels of C1q, C3b, FN, BR1, VCAM-1, E-selectin and FGL-2 got increased gradually. The highest levels for these factors were seen in I4R24 group, followed by I3R24 group, I2.5R24 group, I2R24 group and sham group in order. The rough ratio of the number of positive MPO cells/total cell number under high lens (×200) were increased gradually, with the highest level in I4R24 group, followed by I3R24 group, I2.5R24 group, I2R24 group and sham group in order. However, expression of TF and BR2 were not altered significantly among the groups. Plasma levels of INF-γ, IL-7, IL-18, MIP-1α and MCP-1 elevated gradually with prolongation of ischemia time (all P<0.01). The sequence was the sham group, I2R24 group, I2.5R24 group, I3R24 group and I4R24 groups for levels of these factors from low to high (all P<0.01). Conclusion:Reperfusion after prolongation of ischemia duration can increase the activation of complement, coagulation, kinin and endothelial cells as well as the release of inflammatory factors, and thus aggravate the degree of skeletal muscle tissue injury.
10.Clinical study on the prevention of deep second-degree burn scar with traditional Chinese medicine dressing
Ying LI ; Fangfang JIN ; Haiqiang LU ; Jingqun ZHANG
Chinese Journal of Plastic Surgery 2022;38(6):666-670
Objective:To evaluate the effect of Barker aseptic application on the treatment of deep second-degree burns and scars after healing.Methods:According to the inclusion and exclusion criteria, deep second-degree patients admitted to the Affiliated Hospital of Jining Medical College from September 2016 to September 2019 were randomly divided into treatment and control groups using a random number table method. Barker aseptic application was used for the treatment group, and silver sulfadiazine cream was used for the control group. Patients in two groups were changed dressing every 2 to 3 days. Wound healing time, times of dressing change, pain score during the dressing change, secondary trauma score, and Vancouver Scar Scale (VSS) score at 1, 3, and 6 months after wound healing were compared between the two groups. Differences in patient satisfaction at discharge and 6 months after wound healing were also compared at follow-up. According to the result type of the data, it is expressed as Mean±SD, M( Q1, Q3) or frequency (percentage), and it is described as the t-test, Mann-Whitney U test, or chi-square test. Results:One hundred and thirty-two burn patients were enrolled in each treatment and control group. There were 115 males and 17 females in the treated group, aged (34.5±11.1) years, with the burn surface area accounting for (15.87±8.66)% of the total body surface area (TBSA). 107 males and 25 females were in the control group, aged (32.4±14.1) years, with burn surface area accounting for (16.31±7.06)% TBSA. The healing time of the treated group was significantly shorter than that of the control group [(17.65±5.87) d vs. (23.06±8.78) d, P<0.01], and the VSS scores at 1, 3, and 6 months after wound healing were also lower than that of the control group [5(3, 5) vs. 6(5, 7), 4(3, 5) vs. 6(4, 7), 4(3, 5) vs. 5(4, 6), P<0.01]. In addition, the number of dressing changes, pain scores during dressing changes, and secondary trauma scores in the treatment group were lower than in the control group (all P values<0.01). The satisfaction score and percentage of satisfaction with treatment were higher in the patients at discharge and 6 months of wound healing than in the control group (all P values<0.01). Conclusions:Barker aseptic application can significantly shorten the healing time of deep second-degree burn wounds, reduce scar hyperplasia, improve comfort during dressing changes, and improve patient satisfaction.

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