1.Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targets
Yingzhou SHI ; Hang DONG ; Shiwei SUN ; Xiaoqin WU ; Jiansong FANG ; Jianbo ZHAO ; Junming HAN ; Zhongyue LI ; Huixiao WU ; Luna LIU ; Wanhong WU ; Yang TIAN ; Guandou YUAN ; Xiude FAN ; Chao XU
Clinical and Molecular Hepatology 2024;30(1):80-97
Background/Aims:
To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets.
Methods:
We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options.
Results:
In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018–1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk of primary sclerosing cholangitis (PSC;1.193, 1.048– 1.357). On the other hand, CFHR1 (0.621, 0.497–0.776) and CFHR2 (0.824, 0.703–0.965) were inversely associated with the risk of alcohol-related cirrhosis. There were also significant inverse associations between C8 gamma chain (C8G) and PSC (0.832, 0.707–0.979), as well as the risk of metabolic dysfunction-associated steatotic liver disease (1.167, 1.036–1.314). Additionally, C1S (0.111, 0.018–0.672), C7 (1.631, 1.190–2.236), and CFHR2 (1.279, 1.059–1.546) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network.
Conclusions
Our study suggests that certain complement components, including C1S, C1QC, CFHR1, CFHR2, CFHR5, C7, and C8G, might play a role in non-viral liver diseases and could be potential targets for drug development.
2.Evaluation of clinical efficacy and prognostic factors in multiple myeloma patients treated with auto-HSCT: A single-center real-world study
Zhuoga PINGCUO ; Jianli WANG ; Yan XU ; Wanhong ZHAO ; Pengyu ZHANG ; Jie LIU ; Bo LEI ; Aili HE
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(3):452-459
【Objective】 To evaluate the clinical efficacy and prognostic factors in multiple myeloma (MM) patients treated with autologous hematopoietic stem cell transplantation (auto-HSCT). 【Methods】 The clinical data of 155 MM patients newly diagnosed and suitable for transplantation in our hospital from 2014 to 2021 were retrospectively analyzed. They were divided into auto-HSCT group and non-auto-HSCT group according to the treatment mode. The clinical efficacy, overall survival (OS) and progression-free survival (PFS) of the two groups were compared. Furthermore, the prognostic factors of auto-HSCT group were analyzed. 【Results】 ① There were 51 patients in auto-HSCT group and 104 patients in non-auto-HSCT group. There was no statistical difference in baseline characteristics except age between the two groups. ② Hematopoietic reconstruction was achieved in all patients in auto-HSCT group, and no transplantation-related mortality was found. ③ The clinical efficacy of pre-and post-transplantation was compared in auto-HSCT group. sCR/CR rate was significantly increased after transplantation (P=0.041). The effective remission rate (≥VGPR) was also higher (P=0.05). As for the best efficacy, sCR/CR rate and effective remission rate were both significantly higher in auto-HSCT group than in non-auto-HSCT group (P=0.001). ④ In auto-HSCT group, by the end of follow-up, the median OS was not reached, the median PFS was 30.5 months, and 3-year OS and PFS was 87% and 40.3%, respectively. In non-auto-HSCT group, the median OS was 61 months, the median PFS was 21 months, and 3-year OS and PFS was 65.3% and 33.1%, respectively. It indicated that OS was significantly prolonged in auto-HSCT group (P=0.004). PFS was also prolonged but without significant difference (P=0.065). ⑤ Analysis of prognostic factors in auto-HSCT group showed that decreased PLT (P=0.038) and increased serum-adjusted calcium (P=0.017) were independent risk factors for OS, decreased PLT (P=0.005), female (P=0.018) and disease status of PR or worse before transplantation (P=0.012) were independent risk factors for PFS. 【Conclusion】 Auto-HSCT can improve the remission rate, prolong OS in MM patients, and possibly prolong PFS. Increased serum-corrected calcium and decreased PLT are independent prognostic factors for OS in patients treated with auto-HSCT. Decreased PLT, female, and disease status of PR or worse before transplantation are independent prognostic factors for PFS.
3.Efficacy and safety of autologous hematopoietic stem cell transplantation in patients with multiple myeloma
Ying SHEN ; Fangxia WANG ; Bo LEI ; Jie LIU ; Jianli WANG ; Liufang GU ; Yun YANG ; Pengyu ZHANG ; Xiaorong MA ; Wanhong ZHAO
Journal of Leukemia & Lymphoma 2023;32(12):717-722
Objective:To investigate the efficacy and safety of autologous hematopoietic stem cell transplantation (ASCT) in the treatment of multiple myeloma (MM).Methods:The clinical data of 64 MM patients who received ASCT in the Second Affiliated Hospital of Xi'an Jiaotong University from October 2015 to March 2022 were retrospectively analyzed. The clinical characteristics, therapeutic effects and adverse reactions of the patients were summarized.Results:Of the 64 patients, 42 were male and 22 were female; the median age was 54 years old (37-69 years old). The median number of CD34 + cells collected from 46 patients in the CE (cyclophosphamide, etoposide) regimen mobilization group and 17 patients in the plerixafor mobilization group were 7.50×10 6/kg [(1.15-24.73)×10 6/kg] and 4.54×10 6/kg [(0.75-10.40)×10 6/kg], and the difference was statistically significant ( Z = 3.02, P = 0.024). Hematopoietic reconstitution was successful in all 64 patients, and the median time for white blood cell and platelet engraftment was 11 d (8-13 d) and 11 d (8-15 d), respectively. The patients' pretreatment regimens were all high-dose melphalan, the median white blood cell and platelet engraftment time of 29 patients in the oral group were 11 d (8-13 d) and 11 d (8-15 d), respectively, the median white blood cell and platelet engraftment time of 35 patients in the intravenous infusion group were 11 d (8-12 d) and 11 d (8-15 d), respectively, and there were no statistical differences (both P > 0.05). The ≥CR rate was 48.4% (31/64) before transplantation and 70.3% (45/64) three months after transplantation, and the difference was statistically significant ( χ2 = 6.35, P = 0.012). The median follow-up time of all patients was 27 months (2-67 months). The 3-year OS and PFS rates were 77.6% and 54.9%, and the median OS and PFS time were 67 and 52 months. The median hospitalization time was 20 d (15-37 d). There was no transplantation-related mortality, and the main adverse reactions were gastrointestinal reactions (100.0%, 64/64), grade 4 thrombocytopenia (98.4%, 63/64), grade 4 neutropenia, and agranulocytosis with fever (40.6%, 26/64). Conclusions:ASCT is effective for MM patients suitable for transplantation, which can further improve the remission rate and remission depth, prolong the PFS and OS time of patients, and the adverse reactions are controllable.
4.GC-MS analysis of essential oil extracted from Chimonanthus praecox flowers and exploration of its anti-inflammatory effect
Wenjing DAI ; Chao LUO ; Huifan YU ; Wanhong ZHAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(3):468-473
【Objective】 To clarify the composition of essential oil extracted from Chimonanthus praecox flowers in Shiyan area and to explore its anti-inflammatory effects to provide support for further development of the resources of Chimonanthus praecox flowers. 【Methods】 SD rats were randomly divided into blank control group, model group, positive control group (aspirin 200 mg/kg), and low-, medium- and high-dose essential oil groups (0.1, 0.3 and 0.8g/kg). The blank control group and the model group were treated with distilled water by intragastric administration. The positive control group was treated with aspirin by intragastric administration. The low, medium, and high doses of the essential oil extracted from Chimonanthus praecox flowers were given 10, 30 and 80 mL/L at 10 mL/kg once a day. On day 5 of the experiment, 30 minutes after intragastric administration, 0.1 mL of Freund’s complete adjuvant was injected subcutaneously into the right foot plantar of each group of rats, and the blank control group was subcutaneously injected with 0.1 mL of normal saline. We observed and measured the toe’s volume of the rats before and 1, 2, 3, 5, 24, 48, and 72 h after injection by using drainage method. We then calculated the toe’s swelling rate in each group of rats at each time point, and used ELISA kit to measure the content of inflammatory factors in swollen foot tissue. 【Results】 In the medium- and high-dose essential oil groups, we observed significant inhibitory effects on the toe’s swelling rate in rats at 1, 2, 3, 5, 24, and 48 h after inflammation with Freund’s complete adjuvant (P<0.05). The essential oil extracted from Chimonanthus praecox flowers could significantly decrease the contents of TNF-α and IL-1β in the swollen foot tissue, and its anti-inflammatory effect was dose-dependent. 【Conclusion】 The essential oil extracted from Chimonanthus praecox flowers has obvious inhibitory effects on the rate of the toe’s swelling induced by Freund’s complete adjuvant. The anti-inflammatory effect may be related to the inhibition of TNF-α and IL-1β, but its anti-inflammatory effect is weaker than that of aspirin.
5.Management of cytokine release syndrome related to CAR-T cell therapy.
Hongli CHEN ; Fangxia WANG ; Pengyu ZHANG ; Yilin ZHANG ; Yinxia CHEN ; Xiaohu FAN ; Xingmei CAO ; Jie LIU ; Yun YANG ; Baiyan WANG ; Bo LEI ; Liufang GU ; Ju BAI ; Lili WEI ; Ruili ZHANG ; Qiuchuan ZHUANG ; Wanggang ZHANG ; Wanhong ZHAO ; Aili HE
Frontiers of Medicine 2019;13(5):610-617
Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.
6.Technical specification for clinical application of critical ultrasonography
Wanhong YIN ; Xiaoting WANG ; Dawei LIU ; Yangong CHAO ; Xiangdong GUAN ; Yan KANG ; Jing YAN ; Xiaochun MA ; Yaoqing TANG ; Zhenjie HU ; Kaijiang YU ; Dechang CHEN ; Yuhang AI ; Lina ZHANG ; Hongmin ZHANG ; Jun WU ; Lixia LIU ; Ran ZHU ; Wei HE ; Qing ZHANG ; Xin DING ; Li LI ; Yi LI ; Haitao LIU ; Qinbing ZENG ; Xiang SI ; Huan CHEN ; Junwei ZHANG ; Qianghong XU ; Wenjin CHEN ; Xiukai CHEN ; Daozheng HUANG ; Shuhan CAI ; Xiuling SHANG ; Jian GUAN ; Juan DU ; Li ZHAO ; Minjia WANG ; Song CUI ; Xiaomeng WANG ; Ran ZHOU ; Xueying ZENG ; Yiping WANG ; Liwen LYU ; Weihua ZHU ; Ying ZHU ; Jun DUAN ; Jing YANG ; Hao YANG ; Chinese Critical Ultrasound Study Group ; Gritical Hemodynamic Therapy Collabration Group
Chinese Journal of Internal Medicine 2018;57(6):397-417
Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.
7. Prevalence of inpatients with liver disease in infectious diseases department of three comprehensive hospitals in Yunnan: a multi-center retrospective analysis
Qing CHEN ; Zhibin YANG ; Huiyong SU ; Lihui ZHAO ; Lihong ZHANG ; Hui PENG ; Shuize YIN ; Wanhong MA ; Shiwu MA
Chinese Journal of Hepatology 2018;26(11):819-823
Objective:
To study the constitutional features of diseases spectrum of inpatients with liver disease in infectious diseases department of three comprehensive hospitals to provide resource allocation proposition for the construction of Department of Infectious Diseases.
Methods:
Inpatients data were extracted from the department of infectious diseases of three comprehensive hospitals (Kunming General Hospital of the People's Liberation Army, Yuxi People's Hospital and Dali People's Hospital) between January 2010 to December 2015, and were retrospectively analyzed. The distribution of patients with viral hepatitis (A, B, C, E) and severe liver disease (Severe hepatitis, cirrhosis, liver cancer) was further analyzed in hospitalized patients. Data were analyzed by one-way analysis of variance. A chi-squared test was used for comparison between groups. The change trends of disease constituent ratio in different years were checked by 2 test.
Results:
Liver disease, tuberculosis and AIDS were the three common diseases of three comprehensive hospitals in Yunnan, accounting for 58.61% of all admissions. However, an inpatients with liver diseases (17.25%, 3555/20606, 95% CI 16.73%-17.77%) were significantly lower than tuberculosis inpatients (33.98%, 7002/20606, 95% CI 33.34%-34.62%). An observations from different hospitals and at different time points showed that the proportion of patients with liver disease was lower than that of tuberculosis patients. The proportion of inpatients with HBV infection showed a downward trend (
8.Effect evaluation of quality control circle on shortening DNT in patients with cerebral ischemic stroke
Ruili LI ; Jianping ZHAO ; Wanhong WEI ; Fangfang MA ; Min GUO
China Modern Doctor 2018;56(13):134-136,141
Objective To evaluate the application effect of the quality control circle(QCC) on shortening DNT in patients with cerebral ischemic stroke. Methods QCC activity group had been established and the reasons for the DNT extension in patients with cerebral ischemic stroke were analyzed so as to identify key improvement links and to formulate and to implement countermeasures. Fifteen cases with cerebral ischemic stroke in our hospital before the implementation of QCC from March to April in 2016 were selected as the control group, and 32 cases of patients with cerebral ischemic stroke after the implementation of QCC activities from May to August in 2016 were selected as the observation group. DNT in the two groups of thrombolytic cases were compared, and the more time consuming of emergency, blood test and signature communication were compared and optimized. Results The average DNT of patients with acute cerebral stroke in the observation group was significantly shorter than that in the control group, and the difference was statistically significant (P<0. 05). There were 5 cases with more than 110min DNT in the control group and no case with more than 110min DNT in the observation group, and the difference was statistically significant (P<0. 05). The average time consuming in emergency treatment, blood specimen test and signature communication in the observation group was significantly shorter than that in the control group, and the differences were statistically significant(P<0. 05). Conclusion Through the implementation of QCC can effectively regulate the emergency treatment process of stroke and shorten the DNT in patients with cerebral ischemic diseases.
9.Decoction Amount Changes of Verbascoside and Gallic Acid in Single Decoction and Combined Decoction of Rehmanniae Radix Preparata,Corni Fructus and Poria
Mingming YANG ; Huina WANG ; Hong MIAO ; Wanhong ZHANG ; Guiqin ZHAO
China Pharmacy 2017;28(31):4350-4354
OBJECTIVE:To investigate the decoction amount changes of verbascoside,gallic acid in single decoction and com-bined decoction of rehmanniae radix preparata,corni fructus and poria,and provide scientific basis for further study of effective substance basis. METHODS:The single decoction,combined decoction with each 2 medicine and combined decoction with the 3 medicines of rehmanniae radix preparata,corni fructus and poria,were respectively prepared. HPLC was adopted to detect and com-pare the decoction amount of active component verbascoside in rehmanniae radix preparata and active component gallic acid in cor-ni fructus in each group. RESULTS:Compared with single decoction of rehmanniae radix preparata,the decoction amount of ver-bascoside was decreased in combined decoction of poria+rehmanniae radix preparata(P<0.01),decoction amount of verbascoside was increased in combined decoction of corni fructus+rehmanniae radix preparata or combined decoction with the 3 medicines(P<0.01). Compared with single decoction of corni fructus,the decoction amount of gallic acid in each combined decoction was de-creased (P<0.01). CONCLUSIONS:The combined decoction of rehmanniae radix preparata,corni fructus and poria has certain promotion and inhibition effects on the decoction of verbascoside in rehmanniae radix preparata and inhibition effect on the decoc-tion of gallic acid in corni fructus. It is speculated verbascoside may be one of the main components in combined decoction playing the role of effectiveness.
10.Study on cardiovascular disease risk in inpatients with schizophrenia
Shuai ZHAO ; XiaoQin ZHOU ; Hailong XIA ; Jingjing MU ; Long WANG ; Li ZHU ; Anzhen WANG ; YuXia CHEN ; Wanhong YU
Chinese Journal of Nervous and Mental Diseases 2017;43(9):539-543
Objective To describe the cardiovascular risk profile of inpatients with schizophrenia and estimate the 10-year CVD risk in schizophrenia patients. Methods Four hundred sixty-six randomly selected cases of schizophrenia patients and 507 health controls were included in the study. Body mass index (BMI), Fasting blood glucose (FBG), triglyceride (TG),,total cholesterol (TC), smoking rate (smoking people/total people), Framing-ham Risk Score (FRS), high density lipoprotein-cholesterol (HDL-C) and age of the vessel (VA). The 10-year cardiovascular risk(FRS) and age of the vessel (VA) were assessed using the Framing-ham Risk Score. Results 10-year CVD risk was significantly higher in patients with schizophrenia than in control group [(6.71 ±6.95)% vs. (4.76 ±3.07)%], (P<0.05). Comparing with the control group, smoking prevalence[(41%) vs. (19%)], MS[(25%) vs. (17%)], BMI[(23.67 ±3.61)kg/m2 vs. (21.73±4.11)kg/m2] and VA[(46.7±15.3) vs. (43.7±9.8)] were higher in patients group. SBP[(119.86±14.90)mmHg vs. (128.10±15.41)mmHg] and HDL-C [(1.08±0.27)mmol/L vs. (1.38±0.22)mmol/L] were lower in patients group than in the healthy controls. The FRS score of the patient group was positively correlated with BMI, FBG level and SBP, waist circumference and smoking index (P<0.05) and was negatively correlated with the levels of HDL-C. Multivariate Linear Regression analysis demonstrated that FRS was correlated with FBG (β=0.181,P<0.01)、SBP (β=0.149,P<0.01)、HDL-C (β=-0.107,P<0.01) and smoking index(β=0.554,P<0.01). Conclusion The risk of cardiovascular disease in patients with schizophrenia over the next 10 years is 6.7%, which is significantly higher compared with the control group. Fasting blood glucose, systolic blood pressure, high density lipoprotein, smoking may be associated with 10-year CVD risk of schizophrenia patients.

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