1.Study on the mechanism of hyperoside regulating hepatic lipid synthesis to ameliorate non-alcoholic fatty liver disease in mice
Changrui LONG ; Shijian XIANG ; Zhenhua ZHANG ; Huixing WU ; Benjie ZHOU ; Chengyu LU
China Pharmacy 2025;36(6):668-673
OBJECTIVE To investigate the improvement mechanism of hyperoside (HYP) on non-alcoholic fatty liver disease (NAFLD). METHODS Male C57BL/6 mice were randomly divided into normal (NFD) group, model (HFD) group and HYP group, with 8 mice in each group. Except for NFD group, the mice in other groups were fed with HF60 high-fat diet to establish NAFLD model; HYP group was simultaneously given HYP 100 mg/kg intragastrically every day, for 16 consecutive weeks. The body weight and liver weight of mice in each group were recorded 16 h after the last medication; the histopathological changes and lipid accumulation in the liver were observed, and the contents of triglyceride (TAG) in liver tissue and serum contents of TAG, aspartate transaminase (AST) and alanine transaminase (ALT) were measured; LC-MS/MS method was adopted to detect lipid changes in the liver tissue of mice for lipidomics analysis, and protein expressions of lipid synthesis-associated proteins peroxisome proliferator-activated receptor α (PPARα) were also tested. Human hepatocellular carcinoma cell line HepG2 was divided into normal control group, model group, HYP low-concentration group (50 μmol/L), HYP high-concentration group (100 μmol/L), HYP low-concentration+GW6471 (PPARαinhibitor) group, and HYP high-concentration+GW6471 group. Except for normal control group, the remaining cells were induced with oleic acid and palmitic acid to establish a high-fat cell model. The accumulation of lipid droplets in each group of cells was observed, and the TAG content was detected. RESULTS Compared with HFD group, HYP group exhibited significant reductions in liver fat vacuoles, lipid accumulation, liver weight, and TAG content in liver tissue, as well as serum contents of ALT, AST and TAG (P<0.05). Additionally, the expression of PPARα protein in liver tissue was significantly increased (P<0.05), and the pathological morphological changes associated with NAFLD were alleviated. Lipidomic analysis revealed that HYP significantly reduced the levels of TAG, diacylglycerol and other lipids in the liver. Compared with model group, cellular lipid droplet accumulation and TAG content decreased significantly in HYP low- and high-concentration groups (P<0.05); GW6471 could significantly reverse the improvement effect of HYP on above indicators (P<0.05). CONCLUSIONS HYP can effectively ameliorate NAFLD induced by a high-fat diet in mice, and the mechanism may be related to the activation of PPARα to regulate hepatic lipid synthesis.
2.The constituent elements, experiences, and popularization significance of the palliative care model of integrated elderly care and medical services
Zehuan HUANG ; Mengdong XIN ; Lidan QI ; Long ZHAO ; Minyu WANG ; Lu QIN ; Zhenhua LU ; Zhao LI ; Yue HE ; Xi ZENG
Chinese Medical Ethics 2025;38(7):914-923
Under the trend of increasing aging, integrated elderly care and medical services is an important measure to optimize the supply of elderly care services and promote the good death of the elderly. Using the cooperative production theory and the classical grounded theory, a qualitative analysis was conducted on 38 cases of elderly palliative care and 25 cases of hospital-based palliative care under the integrated elderly care and medical services model from a hospital in Nanning City using Nvivo 20.0 software. This paper found that the integrated elderly care and medical services mode emphasized the deep integration of medical and elderly care services by integrating resources and improving service efficiency, to achieve the basic experience of comprehensive health care for the elderly. The promotion of these experiences has a positive significance for building a multi-agent cooperative production system, strengthening personnel training, perfecting the performance distribution mechanism, and further promoting the development of the national palliative care pilot.
3.Research progress on central memory T cells.
Junwei HUANG ; Wei LU ; Jingxin YAO ; Hanwei DENG ; Ji BIN ; Yuexiang MA ; Zhenhua ZHU
Chinese Journal of Cellular and Molecular Immunology 2025;41(5):468-474
Central memory T (Tcm) cells are a crucial subset in T cell development, playing an important role in long-term immune responses. Tcm cells exhibit strong proliferative capacity, long-term survival characteristics, and re-activation potential, enabling them to rapidly differentiate into effector T cells (Teff) upon antigen re-exposure, thus providing robust immune protection. The function of Tcm cells is regulated by various factors, including antigen exposure, cytokines, and metabolic conditions. A deeper understanding of their metabolic and epigenetic mechanisms under different pathological conditions will contribute to the development of more precise and effective immunotherapeutic strategies. This review elaborates on the origin and characteristics of Tcm cells, as well as their roles in antiviral responses, tumor immunity, and immunotherapy.
Humans
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Memory T Cells/cytology*
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Animals
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Immunologic Memory
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Neoplasms/therapy*
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Immunotherapy
4.Nanomaterials evoke pyroptosis boosting cancer immunotherapy.
Zhenhua LI ; Ziyue XI ; Chuanyong FAN ; Xinran XI ; Yao ZHOU ; Ming ZHAO ; Lu XU
Acta Pharmaceutica Sinica B 2025;15(2):852-875
Cancer immunotherapy is currently a very promising therapeutic strategy for treating tumors. However, its effectiveness is restricted by insufficient antigenicity and an immunosuppressive tumor microenvironment (ITME). Pyroptosis, a unique form of programmed cell death (PCD), causes cells to swell and rupture, releasing pro-inflammatory factors that can enhance immunogenicity and remodel the ITME. Nanomaterials, with their distinct advantages and different techniques, are increasingly popular, and nanomaterial-based delivery systems demonstrate significant potential to potentiate, enable, and augment pyroptosis. This review summarizes and discusses the emerging field of nanomaterials-induced pyroptosis, focusing on the mechanisms of nanomaterials-induced pyroptosis pathways and strategies to activate or enhance specific pyroptosis. Additionally, we provide perspectives on the development of this field, aiming to accelerate its further clinical transition.
5.Serum metabolomics-based study on the mechanism of action of bergapten in the treatment of liver fibrosis
Huixing WU ; Zhenhua ZHANG ; Changrui LONG ; Guifen GUO ; Yanyu WANG ; Yanchun CHEN ; Juxiong FU ; Shijian XIANG ; Benjie ZHOU ; Chengyu LU
China Pharmacy 2024;35(13):1570-1575
OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics. METHODS Forty mice were divided into normal control group (0.5% carboxymethyl cellulose sodium solution), model group (0.5% carboxymethyl cellulose sodium solution), and BP low-dose and high-dose groups (50, 100 mg/kg), with 10 mice in each group. Except for the normal control group, the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model; they were given relevant medicine/solution intragastrically, once a day, for consecutive 8 weeks. After the last medication, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected, and liver pathological changes were observed; the expressions of α-smooth muscle actin (α-SMA) and Collagen Ⅰ were detected in liver tissue; the serum of the mice was collected for metabolomics analysis. RESULTS Compared with the model group, serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups (P<0.05), while liver fibrosis was improved significantly. Meanwhile, metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group, of which 18 substances were upregulated and 157 substances were downregulated; the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism, butanoate metabolism, fatty acid synthesis, tyrosine metabolism, β-alanine metabolism, nicotinic acid and nicotinamide metabolism, glutathione metabolism, etc. CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism, butanoate metabolism, glutathione metabolism and so on in rats with liver fibrosis.
6.Influence of childhood abuse on the presence of depressive symptom in junior high school students: the effecting path of peer attachment and emotional resilience
Xinlong TANG ; Yang JIANG ; Zhenhua LU ; Wanqing YU ; Fan SONG ; Jun ZHANG
Sichuan Mental Health 2024;37(6):526-531
BackgroundDepression as a major mental health condition is commonly found in junior high school students. Peer attachment, emotional resilience and childhood abuse have been found to be associated with depressive symptoms, and it has been hypothesized that peer attachment and emotional resilience may play a chained effecting path in the relationship between childhood abuse and depressive symptoms in junior high school students. ObjectiveTo explore the relationship between childhood abuse and depressive symptom in junior high school students, analyze the effecting path of peer attachment and emotional resilience, thus to provide references for improving the mental health of junior high school students. MethodsFrom May to July 2022, a cluster sampling technique was utilized to recruit 1 781 junior high school students from a junior high school in Anhui province. Childhood Trauma Questionnaire Short Form (CTQ-SF), Revised version of Inventory of Parent and Peer Attachment (IPPA-R), Adolescent' Emotional Resilience Questionnaire (AERQ) and Center for Epidemiological Studies Depression Scale (CES-D) were used as the measurement tools. Pearson correlation coefficient was calculated to assess the correlation among above scales. Process4.2 and Bootstrapping method were employed to verify the effecting path of peer attachment and emotional resilience in the relationship between childhood abuse and depressive symptoms. ResultsCTQ-SF score was negatively correlated with IPPA-R peer attachment subscale score and AERQ score (r=-0.527, -0.495, P<0.01) and positively correlated with CES-D score (r=0.669, P<0.01) in junior high school students. IPPA-R peer attachment subscale score was positively correlated with AERQ score (r=0.556, P<0.01) and negatively correlated with CES-D score (r=-0.599, P<0.01) in junior high school students. AERQ score was negatively correlated with CES-D score (r=-0.698, P<0.01) in junior high school students. Childhood abuse in junior high school students was shown to be a positive predictor of depressive symptoms (β=0.675, P<0.01) and a negative predictor of peer attachment (β=-0.824, P<0.01) and emotional resilience (β=-0.305, P<0.01). Peer attachment and emotional resilience were independent effecting path between childhood abuse and depressive symptoms, with indirect effect size of 0.093 (95% CI: 0.066~0.122) and 0.108 (95% CI: 0.084~0.133), respectively. Peer attachment and emotional resilience affected as a chain effecting path between childhood abuse and depressive symptoms, with indirect effect size of 0.087 (95% CI: 0.071~0.105), accounting for 12.89% of the total effect. ConclusionChildhood abuse in junior high school students can affect the presence of depressive symptom both directly and indirectly through either separate or chained effecting path of peer attachment and emotional resilience. [Funded by 2020 Provincial General Scientific Research Project of West Anhui Health Vocational College (number, KJ2020B006); 2024 Provincial University Natural and Humanities Sciences Research Project of West Anhui Health Vocational College (number, 2024AH053467)]
7.Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer
Shi QIU ; Yaqi QIU ; Linghui DENG ; Ling NIE ; Liming GE ; Xiaonan ZHENG ; Di JIN ; Kun JIN ; Xianghong ZHOU ; Xingyang SU ; Boyu CAI ; Jiakun LI ; Xiang TU ; Lina GONG ; Liangren LIU ; Zhenhua LIU ; Yige BAO ; Jianzhong AI ; Tianhai LIN ; Lu YANG ; Qiang WEI
Chinese Medical Journal 2024;137(2):209-221
Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.
8.Conversion of stromal vascular fraction in the microenvironment of radiation-induced skin injuries and its clinical implications
Lu AN ; Xiaoming CHEN ; Can LI ; Jian YAO ; Shuyu ZHANG ; Jianping CAO ; Zhenhua GONG ; Daojiang YU
Chinese Journal of Radiological Medicine and Protection 2024;44(3):181-187
Objective:To investigate the conversion of stromal vascular fraction (SVF) in the microenvironment of radiation-induced skin injuries to provide guidance for clinical applications.Methods:Based on a random number table, C57BL/6N mice were categorized into four groups: the blank control, negative control, acute injury, and chronic injury groups, with each group containing 25 mice. The backs of mice in the blank control, acute injury, and chronic injury groups were exposed to 15 Gy X-ray irradiation. Then, the mice in the negative control, acute injury, and chronic injury groups were injected subcutaneously with the SVF derived from B6/G-R mice. The survival of these mice was observed 1, 3, 7, 14, and 21 d after the injection through fluorescence tracing and in vivo imaging. Accordingly, the clinical SVF injection regimens were optimized based on the experimental result of mice. Finally, local SVF injection was performed on different frequencies for patients in different wound conditions, with the efficacy being observed. Results:The fluorescence of SVF was observed from the tissue slices of the acute injury, chronic injury, and negative control groups 14 d post-injection. The result showed that the fluorescence intensity of SVF 1, 3, and 7 d post-injection was in the order of the negative control group > the acute injury group > the chronic injury group. The acute injury group ranked at the top and the chronic injury group remained at the bottom 14 d after the injection. The fluorescence of SVF in each group was barely detected 21 d after the injection. Compared to the negative control group, the acute injury group exhibited statistical differences only 14 d post-injection ( t = 4.11, P < 0.05), while the chronic injury group displayed statistical differences 1, 3, 7, and 14 d after the injection ( t = 3.88-5.74, P < 0.05). Furthermore, the acute injury group exhibited significantly higher fluorescence intensity of SVF than the chronic injury group ( t = 4.73-8.38, P < 0.05). The half-life of SVF for the negative control, acute injury, and chronic injury groups was 6.336, 6.014, and 2.163 d, respectively. As indicated by the application of SVF transplantation based on traditional surgical protocols in the clinical trial, SVF can significantly promote wound repair, with earlier SVF transplantation being more beneficial for wound healing. Conclusions:The conversion of SVF differs in the microenvironments of acute and chronic radiation-induced skin injuries. This can serve as an essential guide for the administration timing and injection frequency of SVF in clinical applications.
9.Investigation on bacterial endotoxins test of terbutaline sulfate active pharmaceutical gredient
Xinyu WANG ; Zhenhua LIU ; Haixia LU ; Haofang ZHANG
Drug Standards of China 2024;25(4):376-379
Objective:To establish a method for the detection of bacterial endotoxin in terbutaline sulfate active pharmaceutical ingredients(API).Methods:The method of terbutaline sulfate was verified by gel method,and interference test and bacterial endotoxin test were performed on three batches of samples.Results:The limit for terbutaline sulfate API that can be used for bacterial endotoxin test was set as"the amount of endotoxin contained in terbutaline sulfate should be less than 0.50 EU per 1 mg".Conclusion:Limulus gel method can be used to detect bacterial endotoxin of terbutaline sulfate API.
10.Functional outcomes of robot-assisted radical prostatectomy with preservation of pelvic stabilized structure and early elevated retrograde liberation of neurovascular bundle
Xinyang LIAO ; Yige BAO ; Zhenhua LIU ; Lu YANG ; Shi QIU ; Liangren LIU ; Ping HAN ; Qiang WEI
Chinese Journal of Surgery 2024;62(2):128-134
Objectives:To examine the functional outcomes of robot-assisted radical prostatectomy (RARP) with preservation of pelvic floor stabilized structure and early elevated retrograde liberation of the neurovascular bundle (PEEL).Methods:This study was a retrospective cohort study. Between June 1, 2022, and March 20, 2023, 27 cases of RARP with PEEL and 153 cases of RARP with preservation of pelvic floor stabilized structure (PPSS) were included in this study. All patients were males, aged (62.5±5.2) years (range: 50 to 73 years). There were 18 cases of ≤T2b stage and 9 cases of T2c stage. After 1∶1 propensity score matching, the postoperative functional outcomes of 27 cases of RARP with PEEL and 27 cases of RARP with PPSS were compared. All surgeries were performed by a single surgeon and included patients were clinically staged as cT1-2N0M0 without preoperative urinary incontinence or erectile dysfunction. In RARP with PEEL, the prostate was cut near the midline at the front when dissecting the neurovascular bundle, dissection was performed between the visceral layer of the pelvic fascia and the prostatic fascia, preserving the parietal layer and the visceral layer of the pelvic fascia, and the neurovascular bundle was retrogradely released from the apex. The cumulative probability curve was plotted using the Kaplan-Meier method and the Log-rank test was used to compare the differences in functional outcomes between the two groups. Univariate and multivariate analysis with the Cox proportional hazards model was used to compare postoperative urinary continence and sexual function.Results:The recovery time of continence and potency was significantly longer in the PPSS group than in the PEEL group (all P<0.05). The continence rate of the PEEL group was significantly higher than that of the PPSS group (92.59% vs. 68.10%, P=0.026) at 3 months after surgery. The potency rate of the PEEL group was also significantly higher than that of the PPSS group (40.70% vs. 15.10%, P=0.037) at 3 months after surgery. In the univariate analysis, compared to the PPSS technique, the PEEL technique was associated with a shorter recovery time of continence ( HR=1.94, 95% CI: 1.08 to 3.48, P=0.027) and a shorter recovery time of potency ( HR=2.06, 95% CI: 1.03 to 4.13, P=0.042). In the multivariate analysis, the PEEL technique was an independent prognosis factor for postoperative recovery of continence ( HR=2.05, 95% CI: 1.01 to 4.17, P=0.047) and potency ( HR=3.57, 95% CI: 1.43 to 8.92, P=0.007). All the cases of the PPSS group and the PEEL group were performed successfully with negative surgical margins. Conclusion:Compared with PPSS, PEEL may be more conducive to the recovery of urinary continence and sexual function after RARP.

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