1.Exploration the Immune Regulatory Mechanism of Hedysari Radix Based on Network Pharmacology,Molecular Dynamics,and UPLC-MS/MS
Xudong LUO ; Xinrong LI ; Chengyi LI ; Peng QI ; Tingting LIANG ; Xiaoli FENG ; Xu LI ; Jungang HE ; Xiaocheng WEI ; Ruijuan ZHOU ; Xinming XIE
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(3):376-383
		                        		
		                        			
		                        			Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.
		                        		
		                        		
		                        		
		                        	
2.Overexpression of ubiquitin-conjugating enzyme 2T induces radiotherapy resistance in hepatocellular carcinoma by enriching regulatory T cells in the tumor microenvironment
Xinrong HE ; Sili XIONG ; Zhenru ZHU ; Jingyuan SUN ; Chuanhui CAO ; Hui WANG
Journal of Southern Medical University 2024;44(6):1149-1158
		                        		
		                        			
		                        			Objective To investigate the effect of overexpression of ubiquitin-conjugating enzyme 2T(UBE2T)on radiosensitivity of hepatocellular carcinoma(HCC).Methods Hepa1-6 cells were transfected with a UBE2T-overexpressing or a control lentiviral vector,and the changes in their radiotherapy sensitivity and concentrations of glucose and lactate in the supernatant were assessed using colony-forming assay and colorimetric assay.The transfected cells were inoculated subcutaneously in nude mice or C57BL/6 mice,and tumor growth following irradiation were recorded.The xenografts were collected for analyzing infiltration of CD4+T cells and regulatory T cells(Tregs)using flow cytometry and detecting expressions of HK1 and LDHA using Western blotting.The correlations of UBE2T expression with immune cell infiltration,glycolysis and Tregs in HCC were analyzed using CIBERSORT algorithm and TCGA database,and the results were verified in a co-culture system of Hepa1-6 cells and Tregs.Results UBE2T overexpression caused radiotherapy resistance in both cultured Hepa1-6 cells and xenografts in the tumor-bearing mouse models(especially in C57BL/6 mice).CIBERSORT analysis suggested that a high expression of UBE2T was associated with increased percentages of dendritic cells,T follicular helper cells,M2 macrophages,monocytes,lymphocytes and Tregs in HCC.The UBE2T-overexpressing xenografts showed an increased percentage of Tregs and enhanced expressions of HK1 and LDHA,and irradiation increased infiltration of CD4+T cells and Tregs in the tumor microenvironment.Hepa1-6 cells overexpressing UBE2T showed a decreased glucose concentration and an increased lactate concentration.GSEA analysis suggested that a high UBE2T expression was positively correlated with increased glycolysis and Tregs infiltration in HCC.In the cell co-culture system,UBE2T overexpression significantly enhanced lactate production,proliferation and immunosuppressive functions of Tregs.Conclusion A high UBE2T expression results in radiotherapy resistance of HCC possibly by enhancing glycolysis and cause enrichment of Tregs in the tumor microenvironment.
		                        		
		                        		
		                        		
		                        	
3.Overexpression of ubiquitin-conjugating enzyme 2T induces radiotherapy resistance in hepatocellular carcinoma by enriching regulatory T cells in the tumor microenvironment
Xinrong HE ; Sili XIONG ; Zhenru ZHU ; Jingyuan SUN ; Chuanhui CAO ; Hui WANG
Journal of Southern Medical University 2024;44(6):1149-1158
		                        		
		                        			
		                        			Objective To investigate the effect of overexpression of ubiquitin-conjugating enzyme 2T(UBE2T)on radiosensitivity of hepatocellular carcinoma(HCC).Methods Hepa1-6 cells were transfected with a UBE2T-overexpressing or a control lentiviral vector,and the changes in their radiotherapy sensitivity and concentrations of glucose and lactate in the supernatant were assessed using colony-forming assay and colorimetric assay.The transfected cells were inoculated subcutaneously in nude mice or C57BL/6 mice,and tumor growth following irradiation were recorded.The xenografts were collected for analyzing infiltration of CD4+T cells and regulatory T cells(Tregs)using flow cytometry and detecting expressions of HK1 and LDHA using Western blotting.The correlations of UBE2T expression with immune cell infiltration,glycolysis and Tregs in HCC were analyzed using CIBERSORT algorithm and TCGA database,and the results were verified in a co-culture system of Hepa1-6 cells and Tregs.Results UBE2T overexpression caused radiotherapy resistance in both cultured Hepa1-6 cells and xenografts in the tumor-bearing mouse models(especially in C57BL/6 mice).CIBERSORT analysis suggested that a high expression of UBE2T was associated with increased percentages of dendritic cells,T follicular helper cells,M2 macrophages,monocytes,lymphocytes and Tregs in HCC.The UBE2T-overexpressing xenografts showed an increased percentage of Tregs and enhanced expressions of HK1 and LDHA,and irradiation increased infiltration of CD4+T cells and Tregs in the tumor microenvironment.Hepa1-6 cells overexpressing UBE2T showed a decreased glucose concentration and an increased lactate concentration.GSEA analysis suggested that a high UBE2T expression was positively correlated with increased glycolysis and Tregs infiltration in HCC.In the cell co-culture system,UBE2T overexpression significantly enhanced lactate production,proliferation and immunosuppressive functions of Tregs.Conclusion A high UBE2T expression results in radiotherapy resistance of HCC possibly by enhancing glycolysis and cause enrichment of Tregs in the tumor microenvironment.
		                        		
		                        		
		                        		
		                        	
4.Perioperative diagnosis and treatment strategies of liver transplantation for liver cancer in precision medicine era
Jian ZHOU ; Yifeng HE ; Xiaowu HUANG ; Xinrong YANG
Chinese Journal of Digestive Surgery 2022;21(2):205-209
		                        		
		                        			
		                        			Tumor recurrence and metastasis after liver transplantation (LT) remains one of the most important factors that affect the outcome of LT for hepatocellular carcinoma (HCC). The diagnosis and treatment strategies in the era of precision medicine, including utilizing multi-omics, high-throughput gene sequencing analysis, big data and artificial intelligence to select the biomarkers which can accurately predict the prognosis after LT, evaluating the immune status comprehensively, inducing immune tolerance, providing effective prevention for patients at a high risk of recurrence with sensitive antitumor drugs and attaching importance to individualized treatment for recurrence and metastasis, may further improve the outcome of LT. Combined with experience and review of relevant research articles, the authors elaborate perioperative diagnosis and treatment strategies of LT for HCC, aiming to promote the application of precision medicine in the field of LT.
		                        		
		                        		
		                        		
		                        	
5.Expert guidance on overall management of liver cancer during the COVID-19
Huichuan SUN ; Xinrong YANG ; Zhiping YAN ; Zhenggang REN ; Rong LIU ; Lan ZHANG ; Yang XU ; Yifeng HE ; Zihan ZHANG ; Jia FAN ; Jian ZHOU
Chinese Journal of Digestive Surgery 2022;21(5):557-563
		                        		
		                        			
		                        			The pandemic of Corona Virus Disease 2019 (COVID-19) continues, which shows the concentrated or sporadic cases in multiple places. Current COVID situation is still complex. During the COVID-19, routine diagnosis and treatment of liver cancer patients has been affected in different degrees. Under the premise of following the treatment guidelines, how to reduce the risk of infection of patients and medical staff, utilize limited medical resources to maximally ensure anti-tumor treatment and related emergency treatment, and help patients get through the epidemic period is a problem for liver oncologists. Thus, experts of liver cancer treatment related disciplines of Zhongshan Hospital, Fudan University have written the Expert guidance on overall management of liver cancer during the COVID-19, which aims to provide references for liver oncolo-gists to conduct clinical work safely and effectively under the epidemic prevention and control, and to help patients fight against the epidemic smoothly.
		                        		
		                        		
		                        		
		                        	
6.Clinical characteristics and misdiagnosis analysis of infectious mononucleosis in children
Ruiqing LIU ; Zhaoning SUN ; Tiantian TANG ; Yufeng ZHANG ; Jun WANG ; Pengfei XU ; Xiru YANG ; He SONG ; Jie LI ; Xinrong SUN
Chinese Journal of Postgraduates of Medicine 2022;45(9):777-782
		                        		
		                        			
		                        			Objective:To summarize the clinical characteristics, causes of misdiagnosis and preventive measures of infectious mononucleosis (IM) in children, and to improve the ability of clinicians in early diagnosis of IM in children.Methods:The clinical data of 468 children with IM in Xi′an Children′s Hospital from January 2018 to December 2021 were retrospectively analyzed, including general situation, disease onset, diagnosis and misdiagnosis.Results:Among the 468 children, 33 cases were clinically diagnosed and 435 cases were a definitely diagnosed; 281 males (60.04%) and 187 females (39.96%); the incidence rate was highest in preschool children (43.80%, 205/468) and in autumn (33.12%, 155/468). The first symptoms were fever (52.99%, 248/468), eyelid edema (15.38%,72/468) and neck mass (14.96%, 70/468). The fever rate was 90.38% (423/468), and the median time of first fever appearance was on the first (first, second) day of disease course, and the median duration of fever was 6 (4, 8) d. The median time of first visit was on the third (first, fifth) day of disease course, and the time of diagnosis was on the seventh (fifth, ninth) day of disease course. Blood routine examination showed that the proportion of white blood cell count increased was 51.92% (243/468), the proportion of lymphocytes increased was 61.75% (289/468), and the proportion of abnormal lymphocytes increased (≥10%) in peripheral blood was 58.97% (276/468). The lymphocyte subsets of 364 children were detected, the rate of helper T lymphocytes (Th cells) decreased was 80.22% (292/364), the rate of suppressor T lymphocytes (Ts cells) increased was 99.45% (362/364), the value and decreased rate of Th cells/Ts cells were 0.24 (0.16, 0.40) and 100.00% (364/364), rate of B lymphocytes decreased was 93.96% (342/364), rates of natural killer cells decreased and increased were 35.16% (128/364) and 0.55% (2/364). The misdiagnosis rate was 55.13% (258/468), and the misdiagnosis time was on the fifth (fourth, seventh) day of disease course. Among the 258 misdiagnosed children, 105 cases (40.70%) were misdiagnosed as upper respiratory tract infection, 65 cases (25.19%) as acute suppurative tonsillitis, 27 cases (10.47%) as acute cervical lymphadenitis or neck mass.Conclusions:Due to the complex and diverse clinical manifestations of IM in children, it is easy to be misdiagnosed in the early stage of the disease. So, it is necessary for clinicians to master the clinical characteristics of IM in children, constantly improve the level of diagnosis and treatment, and reduce the misdiagnosis rate.
		                        		
		                        		
		                        		
		                        	
7.Expert consensus on marsupialization of cystic lesions of the jaw
TAO Qian ; HE Yue ; LIU Bing ; HOU Jinsong ; NAN Xinrong ; ZHANG Bin ; ZHANG Leitao ; QIAO Bin
Journal of Prevention and Treatment for Stomatological Diseases 2020;28(2):69-72
		                        		
		                        			
		                        			Marsupialization is effective in the treatment of cystic lesions of the jaw. It is a simple operation that can result in minimal trauma, the reduction of postoperative recurrence, and maximum preservation of the surrounding tissue structure and function. However, there is a certain failure rate in clinical treatment due to the improper grasp of indications and nonstandard operation. The highest failure rate reported in the literature is 32.6%. To further standardize the clinical application of marsupialization and improve the success rate of treatment, we put forward an expert consensus of marsupialization in the treatment of jaw cystic lesions by reviewing the domestic and foreign literature and summarizing the experience in marsupialization from some famous domestic experts. In this consensus, we propose three elements of marsupialization: the establishment of the opening, the maintenance of cyst plugs and regular washing. The scope of application of marsupialization includes jaw cysts and cystic ameloblastomas. It is necessary to standardize the position of the opening, the size of the opening and the manufacture of the cyst plug, and a panoramic film or cone beam computed tomography(CBCT) should be used to observe the changes in the cystic cavity before and after operation. A second-stage operation should be performed when the lesion is significantly reduced by more than 50% or at least 5 mm from important structures; furthermore, the teeth of focus should be treated according to the relationship between the lesion and tooth and the type of tooth.
		                        		
		                        		
		                        		
		                        	
8.Study on RAD51 Gene Regulatory Mechanism of Apigenin Affecting Cisplatin Sensitivity to NSCLC A 549 Cells
Lin MO ; Xin LIU ; Huimin YANG ; Xinrong HE ; Xiaolin WANG ; Chunhong TANG
China Pharmacy 2020;31(6):708-714
		                        		
		                        			
		                        			OBJECTIVE:To study the effects and mechanism o f apigenin on cisplatin sensitivity of NSCLC A 549 cells by regulating RAD51 gene. METHODS :Human lung cancer cisplatin-resistant cells A 549/DDP were selected and divided into control group(blank culture medium ),cisplatin group (5 g/L),apigenin low-dose and high-dose groups (10,20 μmol/L). MTT assay was used to detect the growth of A 549/DDP cells ,while the Annexin Ⅴ/PI double staining combined with flow cytometry were used to detect the apoptosis. A 549/DDP cells were collected and divided into cisplatin alone group (1,2,4,8,16 μg/mL), apigenin combination group (10 μmol/L,based on cisplatin ). MTT method was used to determine and calculate inhibitory rate of cell proliferation. IC 50 values of drugs were calculated by regression model ,and reversion index of apigenin was calculated. 18 nude mice were randomly divided into control group ,cisplatin alone group and apigenin combination group ,with 6 mice in each group. After A 549/DDP cells were inoculated to form the transplanted tumor ,normal saline ,cisplatin(2 mg/kg,once every other day ), cisplatin(the same dosage and usage )+apigenin solution (30 mg/kg,once a day )were injected intraperitoneally respectively. After 18 days of continuous administration ,the body weight of mice and the mass of the transplanted tumor were detected and the tumor inhibition rate was calculated. Human lung cancer cells A 549 and A 549/DDP were collected and divided into normal group (A549 cells),control group (A549/DDP cells ),cisplatin group (5 g/L,A549/DDP cells )and apigenin low-dose and high-dose groups (10,20 μmol/L,A549/DDP cells ),respectively. mRNA and protein expression of RAD51 were detected by real-time fluorescence quantitative PCR and Western blotting assay. RESULTS : Δ 基金项目:四川省教育厅(自筹经费)科研项目(No.12ZB227) *讲师,硕士。研究方向:肿瘤病理。E-mail:molin212@163.com Compared with control group ,the cell growth of apigenin # 通信作者:副教授,硕士生导师,硕士。研究方向:肿瘤病理。 low-dose and high-dose groups were decreased significantly , E-mail:xinrongH292@163.com apoptosis rates of them w ere increased significantly and higher ·708· China Pharmacy 2020Vol. 31 No. 6 中国药房 2020年第31卷第6期 than those of cisplat in group (P<0.05 or P<0.01). After combined with apigenin ,proliferation inhibition rate of A 549/DDP cells was increased significantly ,compared with cisplatin alone group with the same concentration (P<0.05). The IC 50 in the apigenin combination group was (5.81±0.47)μg/mL,significantly lower than (14.44±0.52)μg/mL in cisplatin alone group(P<0.05),and reversal index of apigenin was 2.49. The results of nude mice tumor inhibition experiment showed that after combined with apigenin,tumor inhibition rate of A 549/DDP bearing nude mice was 68.72%,significantly lower than 33.82% in cisplatin alone group. Compared with A 549 cells of normal group ,relative expression of RAD51 mRNA and protein were increased significantly in A549/DDP cells of control group (P<0.05). Compared with A 549/DDP cells of control group ,relative expression of RAD51 mRNA and protein in A 549/DDP cells were decreased significantly in apigenin low-dose and high-dose groups (P<0.05). Compared with cisplatin group ,relative expression of RAD51 mRNA and protein in A 549/DDP cells of apigenin low-dose and high-dose group were decreased significantly (P<0.05). CONCLUSIONS :Apigenin can effectively reverse drug resistance of cisplatin-resistant A 549/DDP cells in human lung cancer. The mechanism may be related to the reduction of RAD51 gene transcription and protein expression.
		                        		
		                        		
		                        		
		                        	
9.Overall management strategies for liver cancer patients during the COVID-19 outbreak
Xinrong YANG ; Huichuan SUN ; Yang XU ; Yifeng HE ; Ao HUANG ; Jia FAN ; Jian ZHOU
Chinese Journal of Digestive Surgery 2020;19(3):244-247
		                        		
		                        			
		                        			The Corona Virus Disease 2019 (COVID-19) that occurred December of 2019 has a wide range of impacts, and its epidemic situation is grim. China has a large population of liver cancer, accounting for 50% of new cases of liver cancer worldwide. How to ensure the diagnosis, treatment and rehabilitation of liver cancer patients while preventing and controlling the epidemic situation is an issue that urgently need specialists pay attention to. The authors propose an overall management model for patients with liver cancer, combined with their own experience, in order to guide specialists to safely and effectively carry out clinical diagnosis and treatment of liver cancer during the prevention and control of epidemics, and to help liver cancer patients receive treatment.
		                        		
		                        		
		                        		
		                        	
10. Design and application of ICU core control measures for multi- drug resistance bacteria
Xinli MA ; Xinrong GUO ; Yanping HE ; Ming YAN
Chinese Journal of Practical Nursing 2019;35(9):678-681
		                        		
		                        			 Objective:
		                        			To design a record sheet of the core control measures for multi-drug resistant bacteria in ICU and apply it to clinical practice.
		                        		
		                        			Methods:
		                        			Through consulting the guidelines and literature, we designed the ICU core control measures to execute the record sheet and applied the record sheet to patients with multiple resistant bacteria infection. The implementation rate of the core control measures of medical personnel before and after the use of the record sheet(the awareness rate of medical personnel, the awareness rate of nursing staff, the compliance rate of hand hygiene, the implementation rate of isolation medical orders, the implementation rate of isolation marks, the implementation rate of single room isolation or bedside isolation, and the exclusive implementation rate of items), qualified rate of surface disinfection of articles, qualified rate of use of antimicrobial agents and incidence of multi-drug resistant bacteria infection were compared.
		                        		
		                        			Results:
		                        			After implementing the record sheet using the ICU multi-drug resistant bacteria core control measures, the implementation rate of medical personnel's core control measures, the conformity rate of surface disinfection of articles and the acceptance rate of antimicrobial drug use were all improved, the difference was statistically significant (
		                        		
		                        	
            

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