1.Follow-up study of left heart valve regurgitation after implantation of left ventricular assist device
Junjiang LIU ; Wenrui MA ; Dingqian LIU ; Yun ZHAO ; Lili DONG ; Zhe LUO ; Kefang GUO ; Chunsheng WANG ; Xiaoning SUN
Chinese Journal of Clinical Medicine 2025;32(1):72-77
Objective To explore the valve regurgitation status of left heart after the implantation of left ventricular assist device (LVAD) and its effect on prognosis of patients with LVAD implantation. Methods A total of 35 patients with cardiomyopathy who underwent magnetic levitation LVAD implantation at Zhongshan Hospital, Fudan University from February 2021 to July 2024 were retrospectively selected. Clinical data during hospitalization were collected, including preoperative basic data and postoperative valve regurgitation status. Telephone follow-ups were conducted to monitor patients’ survival status and transthoracic echocardiography was used to assess left valve function. Kaplan-Meier survival curves and log-rank test were employed to compare the survival rate of patients with different levels of valve regurgitation. Results The 35 patients had a mean age of (53.9±11.1) years, with 85.7% male, and 3 patients (8.6%) died during hospitalization. Preoperatively, 17 patients (48.6%) had moderate or greater mitral regurgitation, while all 35 patients had less than moderate aortic regurgitation. One month postoperatively, thirty patients were followed up, among which 24 patients (80%) had less than moderate mitral regurgitation, including 11 cases with alleviated regurgitation compared to pre-surgery; 6 patients (20%) had moderate or greater mitral regurgitation, including 4 cases with stable regurgitation and 2 cases with progression of regurgitation compared to pre-surgery; 2 patients (6.7%) had progression of aortic regurgitation to moderate or greater. The follow-up time was 1.2 (1.0, 2.1) years, with 1-year survival rate of 91.4% and 3-year survival rate of 71.1%. Survival analysis showed that the 3-year survival rate of patients with moderate or greater mitral regurgitation one month postoperatively was significantly lower than that of patients with less than moderate regurgitation (66.7% vs 83.3%, P=0.046). Conclusions After the implantation of magnetic levitation LVAD, most patients showed improvement in mitral regurgitation, while aortic regurgitation remained unchanged. The degree of mitral regurgitation one month postoperatively is associated with prognosis.
2.Textual Research and Analysis of Historic Origin and Ancient and Modern Application of Classic Formula Shengjiangsan
Lyuyuan LIANG ; Jialei CAO ; Xinghang LYU ; Weixiao LI ; Wenxi WEI ; Bingqi WEI ; Zhe WANG ; Yiping WANG ; Bingxiang MA ; Wenli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):219-227
Shengjiangsan is a classic formula for treating warm diseases with wide clinical application and accurate efficacy. There are different opinions on the origin of this formula and lacks key information research on this formula. Therefore, in this study, we conducted systematic research into the historic origin, composition, and other key information of this Shengjiangsan. Results showed that Shengjiangsan has different versions, with "Neixian Fufang", "Jiawei Jianghuangwan", "Peizhensan", and "Taijiwan" being the same formula with different names. Shengjiangsan was first recorded as "Neixian Fufang" in Wanbing Huichun written by GONG Tingxian from the Ming dynasty, inherited and developed by YANG Lishan from Qing dynasty, and has been passed down to modern times. Pills and powder are two main forms of Shengjiangsan, and powder has become more popular nowadays. According to the measurement system of Ming and Qing dynasties, the recommended dosage and usage of Shengjiangsan are as follows. For the pill version of Shengjiangsan, Bombyx Batryticatus of 74.6 g, Curcumae Longae Rhizoma of 9.325 g, Cicadae Periostracum of 9.325 g, and Rhei Radix et Rhizoma of 149.2 g were processed into pills for preparation. Single dosage is Bombyx Batryticatus of 1.15 g, Curcumae Longae Rhizoma of 0.14 g, Cicadae Periostracum of 0.14 g, and Rhei Radix et Rhizoma of 2.3 g, with halved dosage applied for children. For the powder version of Shengjiangsan, the dosage varied in accordance with the severity of the disease. Bombyx Batryticatus of 1.84 g, Curcumae Longae Rhizoma of 0.28 g, Cicadae Periostracum of 0.92 g, and Rhei Radix et Rhizoma of 3.68 g were processed into powder for patients with mild symptoms. Bombyx Batryticatus of 2.48 g, Curcumae Longae Rhizoma of 0.37 g, Cicadae Periostracum of 1.23 g, and Rhei Radix et Rhizoma of 4.91 g were processed into powder for patients with severe symptoms. Bombyx Batryticatus of 3.68 g, Curcumae Longae Rhizoma of 1.84 g, Cicadae Periostracum of 0.55 g, and Rhei Radix et Rhizoma of 7.36 g were processed into powder for patients with critical conditions. In this formula, four herbs were ground to fine powder. For patients with mild symptoms, the whole formula was divided into four dosages, and each dosage weighed 6.71 g. The 200 mL yellow rice wine and 18.65 g honey were added, and the solution was stirred and taken cold till full recovery. For patients with severe symptoms, the whole formula was divided into three dosages, and each weighed 8.95 g. 300 mL yellow rice wine and 27.98 g honey were added, and the solution was stirred and taken cold. For patients with critical conditions, the whole formula was divided into two dosages, and each weighed 13.43 g. 400 mL yellow rice wine and 37.3 g honey were added, and the solution was stirred and taken cold. Shengjiangsan has the effect of ascending lucidity and descending turbidity, dissipating wind, and clearing heat. It is specialized in treating severe heat in exterior, interior, and triple energizers in warm diseases and has a wide modern clinical application. In this study, the historic evolution and key information of Shengjiangsan were reviewed and analyzed, and the key information table of Shengjiangsan was attached, serving as a reference for scholars' research and a theoretical basis for its market transformation.
3.Modulation of colonic DNA methyltransferase by mild moxibustion and electroacupuncture in ulcerative colitis TET2 knockout mice
Gege FENG ; Yue ZHANG ; Huangan WU ; Lu ZHU ; Hongxiao XU ; Zhe MA ; Yan HUANG
Digital Chinese Medicine 2025;8(1):100-110
Objective:
To investigate the mechanism of in alleviating colonic mucosal inflammation in ten-eleven translocation (TET) protein 2 gene knockout (TET2-/-) mice with ulcerative colitis (UC) by regulating DNA methyltransferase (DNMT) and DNA hydroxymethylase.
Methods:
Male specific pathogen-free (SPF) grade C57BL/6J wild-type (WT) mice (n = 8) and TET2-/- mice (n = 20) were used to establish UC models by freely drinking 3% dextran sulfate sodium solution for 7 d. After UC model validation through histopathological examination in two mice from each type, the remaining mice were divided into four groups (n = 6 in each group): WT model (WT + UC), TET2-/- model (TET2-/- + UC), TET2-/- mild moxibustion (TET2-/- + MM), and TET2-/- electroacupuncture (TET2-/- + EA) groups. TET2-/- + MM group received mild moxibustion on Tianshu (ST25) and Qihai (CV6) for 10 min daily for 7 d. The TET2-/- + EA group also applied electroacupuncture (1 mA, 2/100 Hz) at the same acupoints for 10 min daily for 7 d. The disease activity index (DAI) scores of each group of mice were accessed daily. The colon lengths of mice in groups were measured following intervention. The pathological changes in the colon tissues were observed with hematoxylin and eosin (HE) staining. The concentrations of interleukin (IL)-6, C-C motif chemokine 17 (CCL17), and C-X-C motif chemokine ligand 10 (CXCL10) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression of DNMT proteins (DNMT1, DNMT3A, and DNMT3B) in the colon tissues was detected by immunohistochemistry. The expression of 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC), histone deacetylase 2 (HDAC2), and DNA hydroxymethylase family proteins (TET 1 and TET3) was detected using immunofluorescence, which also determined the co-localization of TET1 and IL-6 protein.
Results:
Compared with WT + UC group, TET2-/- + UC group exhibited significantly higher DAI scores and shorter colon lengths (P < 0.01). Both mild moxibustion and electroacupuncture significantly decreased DAI scores and ameliorated colon shortening in TET2-/- mice (P < 0.001). Histopathological scores of TET2-/- + UC mice were significantly higher than those of WT + UC group (P < 0.001) and were significantly reduced after both mild moxibustion and electroacupuncture interventions (P < 0.001). Serum levels of IL-6, CCL17, and CXCL10 were significantly elevated in TET2-/- + UC group compared with WT + UC group (P < 0.001). Mild moxibustion significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.001, P < 0.001, and P < 0.01, respectively), while electroacupuncture also significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.05, P < 0.01, and P < 0.01, respectively). TET2-/- + UC mice showed increased expression levels of DNMT1, DNMT3A , DNMT3B, and 5-mC (P < 0.05, P < 0.01 and P < 0.001, respectively), with decreased expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001). Mild moxibustion significantly reduced DNMT1, DNMT3B, and 5-mC levels (P < 0.05, P < 0.01, and P < 0.001, respectively), while increasing expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001, P < 0.001, P < 0.05, and P < 0.001, respectively). Electroacupuncture significantly decreased 5-mC and DNMT3B levels (P < 0.001 and P < 0.01, respectively) and increased 5-hmC and HDAC2 levels (P < 0.05 and P < 0.001, respectively), but did not significantly affect TET1 and TET3 expression (P > 0.05). Compared with TET2-/- + MM group, TET2-/- + EA group showed significantly higher 5-mC expression (P < 0.001). TET2-/- + UC group exhibited markedly increased IL-6 expression and higher co-localization of TET1 and IL-6 in mucosal epithelium, whereas minimal IL-6 expression was observed in the other groups.
Conclusion
Mild moxibustion and electroacupuncture significantly ameliorate colonic inflammation exacerbated by TET2 deficiency in UC mice via epigenetic modulation. Distinct mechanisms exist between the two interventions: mild moxibustion regulates both DNMT and hydroxymethylase, whereas electroacupuncture primarily affects DNMT.
4.IL2rg-/- rats support prolonged infection of human RSV
Rui XIONG ; Yong WU ; Yanwei YANG ; Zhe QU ; Susu LIU ; Yuya WANG ; Liying MA ; Rui FU ; Yihong PENG ; Chunnan LIANG ; Changfa FAN
Acta Laboratorium Animalis Scientia Sinica 2024;32(1):17-24
Objective To overcome the limitations of existing human respiratory syncytial virus(hRSV)animal models,such as semi-permissiveness and short duration of infection,this study established an IL2rg gene knockout(IL2rg-/-)rat model using TALEN gene editing technology.Methods The animal model was infected with hRSV intranasally.Clinical characteristics,body weight,and temperature changes were observed over the infection period(0~35 days).The total viral loads in respiratory organs,such as the nasal tissue,trachea,and lungs,were measured at various time points(4,11,20,and 35 days post-infection).Pathological analysis was conducted on target organs at the endpoint of observation(35 days post-infection).Changes in peripheral blood T,B,NK,and NKT cells and various cytokines were assessed at various time points(4,20,and 35 days post-infection).Results(1)IL2rg/-knockout rats sustained high viral loads in the nasal cavity upon intranasal inoculation with hRSV.The average peak titer rapidly reached 1 × 1010 copies/g in nasal tissue and 1 × 107 copies/g up to 5 weeks post-infection.(2)However,no significant pathological changes were noted in nasal,tracheal,or lung tissues.(3)An increase was observed in the content of peripheral blood B cells in hRSV-infected IL2rg--rats.(4)IL-6 and MCP-1 were increased in the early stage of infection and then decreased at the end of the observation period.Conclusions This study established a new IL2rg-/-rat model using TALEN technology and found that this model effectively supported high-level replication and long-term infection of hRSV,providing a good basis for antiviral drug screening and in vivo efficacy evaluation of anti-hRSV antibodies.
5.Expression patterns of transcription factor TFAP2B in epidermal melanocytes in healthy individuals and vitiligo patients
Jingjing MA ; Pan KANG ; Sen GUO ; Zhe JIAN ; Chunying LI ; Shuli LI
Chinese Journal of Dermatology 2024;57(1):29-33
Objective:To explore expression patterns of transcription factor TFAP2B in epidermal melanocytes of healthy individuals and vitiligo patients.Methods:Lesional tissues were collected from 5 patients confirmedly diagnosed with progressive vitiligo at the Department of Dermatology, Xijing Hospital, Air Force Medical University from January 2020 to December 2022. At the same time, some discarded normal skin tissues were obtained from 5 gender- and age-matched healthy individuals after plastic surgeries. The immortalized healthy human epidermal melanocyte cell line PIG1, the vitiligo epidermal melanocyte cell line PIG3V, and primary human epidermal melanocytes, which were isolated from the discarded foreskin tissues of 3 healthy males after urological surgeries in Xijing Hospital, were cultured in vitro. Tissue immunofluorescence assay was performed to determine the expression and localization of TFAP2B and dopachrome tautomerase (DCT) in healthy skin tissues and vitiligo lesions, and cell immunofluorescence assay and Western blot analysis were conducted to determine the TFAP2B expression in human epidermal melanocytes. Comparisons between two groups were performed using t test, and correlation analysis was performed using Pearson correlation coefficients. Results:Tissue immunofluorescence assay showed that TFAP2B was specifically expressed in human epidermal melanocytes and localized in the nuclei. Western blot analysis showed that TFAP2B was strongly expressed in the human epidermal melanocyte cell line PIG1 and primary melanocytes, with the relative expression levels being 0.45 ± 0.05 and 0.36 ± 0.04, respectively. Tissue immunofluorescence analysis showed that the fluorescence intensity of TFAP2B (623 917.5 ± 88 784.0) was significantly and positively correlated with that of DCT (2 232 655.3 ± 588 810.4; r = 0.91, P < 0.001) in human epidermal tissues from 5 healthy controls and 5 vitiligo patients. In addition, the relative fluorescence intensity of TFAP2B in epidermal melanocytes was significantly lower in the vitiligo lesions (0.12 ± 0.05) than in the healthy skin tissues (1, t = 19.35, P < 0.001). Western blot analysis showed that the relative expression level of TFAP2B was also significantly lower in the PIG3V cells (0.62 ± 0.09) than in the PIG1 cells (1, t = 5.92, P < 0.027) . Conclusions:TFAP2B was specifically and highly expressed in human epidermal melanocytes, and its expression level was significantly and positively correlated with that of the melanocyte marker DCT. Additionally, TFAP2B was obviously lowly expressed in the epidermal melanocytes of patients with vitiligo.
6.Study of the mechanism of acupuncture and moxibustion in protecting the intestinal mucosal barrier in DSS-induced UC rats based on the IL-9/IL-9R pathway
Yan HUANG ; Kexin SUN ; Jing XU ; Zhe MA ; Jimeng ZHAO ; Lingjie LI ; Chen ZHAO ; Ling YANG ; Feng LI ; Yanan LIU ; Yue ZHANG ; Luyi WU ; Rude HUANG
Journal of Acupuncture and Tuina Science 2024;22(2):91-103
Objective:To observe the effects of acupuncture and moxibustion on interleukin(IL)-9/IL-9 receptor(IL-9R)in the colon tissue of rats with ulcerative colitis(UC)and investigate the protective mechanism of acupuncture and moxibustion on the intestinal mucosal barrier in UC rats. Methods:Male Sprague-Dawley rats were randomly divided into a normal control(NC)group and a modeling group.UC models were prepared by giving 4%dextran sulfate sodium(DSS)water for 7 d.After the successful construction of the UC rat model,the modeling group was randomly divided into a UC group,a herb-insulated moxibustion(HM)group,and an electroacupuncture(EA)group.HM and EA interventions at bilateral Tianshu(ST25)were performed once a day for 7 d.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in the colon.The serum concentrations of IL-9,IL-6,IL-1β,and hemoglobin-H(HbH)were determined by enzyme-linked immunosorbent assay.The protein expression levels of IL-9,IL-9R,claudin-2,zonula occludens-1(ZO-1),and occludin in the colon tissue were measured by Western blotting or immuno-histochemistry.Immunofluorescence was used to detect the co-expression of PU.1 and CD4 with the IL-9 protein. Results:Compared with the NC group,the colon tissue of UC rats was severely damaged and ulcerated with congestion and edema,and the colonic histopathological score increased significantly(P<0.01).The serum HbH concentration decreased significantly(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β increased(P<0.01).The protein expression of colonic ZO-1 and occludin decreased significantly(P<0.01),while the protein expression of colonic IL-9 and IL-9R increased(P<0.05).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 increased in the colon tissue(P<0.05).Compared with the UC group,the colonic mucosal structures were gradually repaired in both HM group and EA group,and healed ulcers could be observed,the colonic histopathological score decreased significantly(P<0.05).The serum concentration of HbH increased(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β decreased(P<0.05).The protein expression levels of ZO-1 and occludin increased(P<0.05),while the protein expression levels of IL-9 and IL-9R decreased(P<0.01).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 decreased in the colon tissue(P<0.05). Conclusion:Both HM and EA can inhibit the protein expression levels of IL-9 and IL-9R in the UC colon by regulating the transcription factor PU.1,promote the repair of intestinal mucosal barrier,and down-regulate protein contents of proinflammatory factors IL-9,IL-6,and IL-1β in the serum,which may be one of the key mechanisms of acupuncture and moxibustion in reducing the inflammation of UC colonic mucosa and protecting the intestinal mucosal barrier.
7.Research status of traditional Chinese medicine intervention in mTOR pathway targeting autophagy for prevention and treatment of diabetic nephropathy
Shi-Rui YANG ; Ting-Ting ZHOU ; Chao-Chao MA ; Peng-Fei YANG ; Fan-Qi NIU ; Xue-Yang DU ; Feng-Zhe YAN ; Si-Nong WANG
The Chinese Journal of Clinical Pharmacology 2024;40(11):1675-1678
Diabetic kidney disease(DKD)is one of the most important complications of diabetes.In recent years,domestic and foreign studies have found that mammalian target protein of rapamycin(mTOR)related signaling pathway is a classic pathway involved in the regulation of autophagy,which can achieve the therapeutic effect of DKD by targeting the autophagy pathway,and plays a crucial role in the prevention and treatment of DKD.In this paper,we reviewed the mechanism of mTOR-related signaling pathway targeted autophagy in the prevention and treatment of DKD,in order to provide a new reference and basis for clinical prevention and treatment of DKD.
8.Study of honey-processed Hedysari Radix on the protection of intestinal mucosal barrier in rats with spleen deficiency
Mao-Mao WANG ; Qin-Jie SONG ; Zhe WANG ; Ding-Cai MA ; Yu-Gui ZHANG ; Ting LIU ; Zhuan-Hong ZHANG ; Fei-Yun GAO ; Yan-Jun WANG ; Yue-Feng LI
The Chinese Journal of Clinical Pharmacology 2024;40(15):2231-2235
Objective To explore the protective mechanism of honey-processed Hedysari Radix in regulating intestinal mucosal injury in rats with spleen qi deficiency.Methods The three-factor composite modeling method of bitter cold diarrhea,overwork and hunger and satiety disorder was used to construct a spleen qi deficiency model rats.After the model was successfully made,they were randomly divided into model group,honey-processed Hedysari Radix group and probiotic group,with 15 animals in each group.Another 15 normal rats were taken as the blank group.The honey-processed Hedysari Radix group was given 12.6 g·kg-1 water decoction of honey-processed Hedysari Radix by gavage,the probiotics group was given Bifidobacterium Lactobacillus triple viable tablets suspension at a dose of 0.625 g·kg-1,and the blank group and the model group were given the same dose of distilled water.The rats in the four groups were administered once a day for 15 days.Enzyme-linked immunosorbent assay was used to detect diamine oxidase(DAO)in serum,D-lactic acid(D-LA),secretory immunoglobulin A factor,and Western blotting was used to detect the expression levels of AMP-activated protein kinase(AMPK),zonula occludens-1(ZO-1)and occludin in colon tissues.Results The serum levels of DAO in the blank group,model group,honey-processed Hedysari Radix group and probiotic group were(138.93±9.78),(187.95±12.90),(147.21±6.92)and(166.47±3.37)pg·mL-1;the contents of D-LA were(892.23±49.17),(1 099.84±137.64),(956.56±86.04)and(989.61±51.75)μg·L-1;the contents of SIgA in colon tissues were(14.04±1.42),(11.47±2.39),(11.84±1.49)and(12.93±1.65)μg·mL-1;the relative expression levels of ZO-1 protein in colon tissues were 1.18±0.11,0.42±0.04,0.77±0.05 and 0.95±0.07;the relative expression levels of occludin protein were 1.35±0.31,0.61±0.17,1.19±0.19 and 0.88±0.13;the relative expression levels of AMPK protein were 0.91±0.02,0.35±0.09,0.74±0.08 and 0.59±0.11.Compared with the model group,there were significant differences in the serum content of DAO and D-LA,SIgA content in colon,and the content of ZO-1,occludin and AMPK protein in the honey-processed Hedysari Radix group(P<0.01,P<0.05).Conclusion Honey-processed Hedysari Radix can enhance the protective effect on the intestinal mucosa of rats with spleen qi deficiency by regulating the expression of related inflammatory cytokines,intestinal mucosal upper cell enzymes and tight junction proteins in rats with spleen qi deficiency.
9.Research status of traditional Chinese medicine regulation of mitochondrial autophagy in the treatment of cerebral ischemia-reperfusion injury
Guan-Hua LI ; Yue-Hui MA ; Zhe-Yi ZHOU
The Chinese Journal of Clinical Pharmacology 2024;40(15):2273-2277
Mitophagy has a neuroprotective role in cerebral ischemia/reperfusion(I/R)injury,and the regulation of mitophagy may be an important target for the treatment and improvement of prognosis of cerebral ischemia.In recent years,traditional Chinese medicine(TCM)has developed rapidly,and due to its advantages of fewer side effects,significant curative effect,and multiple targets,the regulation of mitophagy by traditional Chinese medicine to improve I/R has become a research hotspot.This article summarizes the important research progress of TCM monomers and TCM compounds in regulating mitophagy in the treatment of I/R injury in recent years,so as to provide research basis and theoretical guidance for the research on the relationship between TCM and mitophagy in I/R injury.
10.Research status on the mechanism of action of Astragaloside Ⅳ on cardiovascular diseases
Er-Dan XIN ; Yu-Gui ZHANG ; Tian-Tian BIAN ; Ding-Cai MA ; Zhe WANG ; Mao-Mao WANG ; Yue-Feng LI
The Chinese Journal of Clinical Pharmacology 2024;40(17):2580-2585
Asragaloside Ⅳ(AS-Ⅳ)is one of the active ingredients of Astragalus membranaceus,and AS-Ⅳ can play a protective role in cardiovascular diseases by inhibiting inflammatory response,inhibiting cardiomyocyte apoptosis,improving myocardial ischemia reperfusion injury,regulating lipid metabolism,promoting cardiac vascular regeneration,inhibiting myocardial fibrosis,and improving myocardial hypertrophy.In this paper,we reviewed the relevant literature on the prevention and treatment of cardiovascular diseases of AS-Ⅳ,and summarized and analyzed its role and mechanism,in order to provide a reference for the in depth research on cardiovascular diseases and the development and application of drugs.

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