1.Combined application of MS-275 and curcumin in inhibiting cell survival signaling pathways and inducing apoptosis of prostate cancer cells
Zhiyan DU ; Ming ZHAO ; Yuanji XU ; Jian MA ; Xiaodan YU
Medical Journal of Chinese People's Liberation Army 1981;0(06):-
Objective Curcumin and MS-275,an inhibitor of histone deacetylase (HDAC),are promising anti-tumor agents. The aim of present study was to investigate the mechanisms of apoptosis induced by combined use of MS-275 in low dosage and curcumin in prostate cancer cell line DU145. Methods MTT assay was used to evaluate the lethal effect on DU145 cells by solitary use of MS-275 and or combined with curcumin. The changes in cell life cycle was detected by flow cytometry. The expressions of the survival signaling pathways were determined by Western blotting. Results Solitary application of MS-275 or curcumin may inhibit the growth of DU145 cells in a time and dose-dependent manner. The combination of MS-275 (1?mol/L) and curcumin (20?mol/L) exhibited obvious cytotoxic effect on cell viability,which was only 45.9% 48h after the combined treatment. Cell cycle assay showed that the combination of MS-275 and curcumin resulted in obvious appearance of sub-G1 phase in DU145 cells,implying that the cell apoptosis had been induced. The results of Western blotting showed that after treatment of MS-275 or curcumin singly,the phosphorylation level of Akt and ERK kinase declined slightly,however,when MS-275 and curcumin were used together,there appeared a prominent inhibitory effect on Akt and ERK kinase,indicated by a sharp decline of their phosphorylation level,and at the same time,the level of cleaved PARP,a hallmark of apoptosis,was increased in DU145 cells. Conclusion Combined use of MS-275 and curcumin may exert a synergistic cytotoxic effect on the viability of DU145 cells,and exhibit an inhibitory activity on Akt and ERK kinases to induce apoptosis.
2. Research advances in chronicity of hepatitis E virus infection
Chinese Journal of Hepatology 2017;25(10):785-788
Hepatitis E virus (HEV) infection usually causes acute hepatitis and has a self-limiting progression. The patients often recover within 6 months with good prognosis. Recent studies have found that HEV infection may become chronic in special situations, which manifests as persistent liver function abnormalities for at least 6 months after acute HEV infection and the presence of viral nucleic acid in serum, feces, and/or liver tissue. Chronicity of HEV infection mainly occurs in immunocompromised patients, and it is rare but very dangerous in clinical practice. An understanding of the pathogenesis, clinical manifestations, treatment methods, and preventive measures of chronicity of HEV infection helps clinical physicians develop an effective management regimen and improve patient prognosis. This article introduces related issues, in order to raise the awareness of this disease among clinical physicians.
3.Recent advances in simple plasma exchange therapy with regional citrate anticoagulation
Xiaoran LI ; Yuanji MA ; Lang BAI ; Hong TANG
Chinese Journal of Clinical Infectious Diseases 2021;14(6):475-480
Plasma exchange therapy is applied for treatment of severe immune diseases of multiple organ systems and severe liver diseases by removing pathogenic factors and regulating immune function. Regional citrate anticoagulation has no effect on systemic coagulation function and does not increase bleeding risk, and it is one of the optional anticoagulation methods for plasma exchange therapy. This article reviews recent literature on simple plasma exchange therapy with regional citrate anticoagulation to provide a reference for clinical application of this therapy.
4.Anticoagulants for artificial liver support therapy: Application advances and selection strategies
Yuanji MA ; Lingyao DU ; Lang BAI ; Hong TANG
Journal of Clinical Hepatology 2022;38(10):2396-2401
Coagulation disorder is one of the characteristics of liver failure, leading to an unstable and vulnerable "rebalance" state of coagulation function, which may be easily broken by internal or external factors. Anticoagulants are often required during artificial liver support therapy for patients with liver failure, which may break the "rebalance" state and result in bleeding events. This article reviews the methods for evaluating coagulation status in liver failure, the features of available anticoagulants, and the advances in the application of such anticoagulants in artificial liver support therapy and discusses the anticoagulation management and selection strategy for artificial liver support therapy with reference to the selection experience of West China Hospital of Sichuan University.
5.Drugs and hepatitis B virus reactivation.
Lingyao DU ; Yuanji MA ; Hong TANG
Journal of Biomedical Engineering 2022;39(3):627-632
Drugs may induce hepatitis B virus (HBV) reactivation (HBV-R). Here we have reviewed the definition and harm of HBV-R, the risk drugs and their underlying mechanism, the influence factors, as well as the early intervention measures. It is shown that multiple drugs, including chemotherapy drugs, immunotherapy drugs, directly acting antivirals, cell therapy, etc., can induce HBV-R by affecting host immunity or directly activating HBV transcription factors. HBV-R could cause severe liver damage, even interruption of treatment of original diseases, affecting the prognosis of patients. Through precisely identifying risk drugs, monitoring the influence factors, and prescribing preventive anti-HBV regimen if necessary, the incidence of HBV-R can be significantly reduced. It is also suggested that clinical physicians should not only pay attention to the early identification and intervention of HBV-R, but also further study the mechanism of HBV-R in depth, especially the underlying mechanism between host, HBV and risk factors. This will help to promote the discovery of more valuable markers for risk prediction and targets for early intervention, and to further reduce the risk of HBV-R and improve the prognosis of patients.
Hepatitis B virus
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Humans
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Immunotherapy
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Risk Factors
6.Establishment and validation of nomogram prediction model of cefoperazone/sulbactam-induced thrombocytopenia
Hehe BAI ; Lirong PENG ; Yuanji WANG ; Xiaojing NIE ; Jinping WANG ; Li MA ; Guan WANG
China Pharmacy 2024;35(8):980-985
OBJECTIVE To explore the predictive factors of cefoperazone/sulbactam-induced thrombocytopenia in adult inpatients, and to establish and validate the nomogram prediction model. METHODS Data of adult inpatients treated with cefoperazone/sulbactam in Xi’an Central Hospital from Jun. 30th, 2021 to Jun. 30th, 2023 were retrospectively collected. The training set and internal validation set were randomly constructed in a 7∶3 ratio. Singler factor and multifactor Logistic regression analysis were used to screen the independent predictors of cefoperazone/sulbactam-induced thrombocytopenia. The nomogram was drawn by using “RMS” of R 4.0.3 software, and the predictive performance of the model was evaluated by the receiver operating characteristic curve and C-index curve. Hosmer-Lemeshow goodness-of-fit test was used to evaluate the calibration degree of the model. Using the same standard, the clinical data of hospitalized patients receiving cefoperazone/sulbactam in Xi’an First Hospital in the same period were collected for external validation of the nomogram prediction model. RESULTS A total of 1 045 patients in Xi’an Central Hospital were included in this study, among which 67 patients suffered from cefoperazone/sulbactam-induced thrombocytopenia, with an incidence of 6.41%. After the false positive patients were excluded, 473 patients were included finally, including 331 in the training set and 142 in theinternal validation set. Multifactor Logistic regression analysis showed that age [OR=1.043, 95%CI (1.017, 1.070)], estimated glomerular filtration rate (eGFR) [OR=0.988,95%CI(0.977, 0.998)], baseline platelet (PLT) [OR=0.989, 95%CI(0.982, 0.996)], nutritional risk [OR=3.863, 95%CI(1.884, 7.921)] and cumulative defined daily doses (DDDs) [OR=1.082, 95%CI(1.020, 1.147)] were independent predictors for cefoperazone/sulbactam-induced thrombocytopenia (P<0.05). The C-index values of the training set and the internal validation set were 0.824 [95%CI (0.759, 0.890)] and 0.828 [95%CI (0.749, 0.933)], respectively. The results of the Hosmer-Lemeshow test showed that χ 2 values were 0.441 (P=0.802) and 1.804 (P=0.406). In the external validation set, the C-index value was 0.808 [95%CI (0.672, 0.945)], the χ 2 value of the Hosmer-Lemeshow test was 0.899 (P=0.638). CONCLUSIONS The independent predictors of cefoperazone/sulbactam-induced thrombocytopenia include age, baseline PLT, eGFR, nutritional risk and cumulative DDDs. The model has good predictive efficacy and extrapolation ability, which can help clinic identify the potential risk of cefoperazone/sulbactam-induced thrombocytopenia quickly and accurately.