OBJECTIVES: To investigate the molecular mechanism by which Lichong Xiaozheng Granules (LCXZ) sensitize ovarian cancer to cisplatin (DDP) treatment. METHODS: LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage. In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts, the effects of daily gavage of distilled water (control group), intraperitoneal injection of DDP (5 mg/kg) once a week, or both DDP injection and daily LCXZK gavage (15 g/kg) on tumor growth were evaluated. Histopathological changes in the xenografts and kidneys were assessed with HE staining. RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis. The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting. RESULTS: A total of 218 blood-borne components of LCXZ were detected by LC-MS. In the tumor-bearing mice, treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3% and 72.6% compared with that in the control group, respectively. Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups. Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3 (ANT3) with binding energies below -6 kcal/mol. Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice, and these changes were more pronounced in the combined treatment group. The expression levels of BAX, ANT3, cleaved caspase-3 and cleaved caspase-9 were increased, whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups. CONCLUSIONS LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.
Animals ; Female ; Cisplatin/pharmacology* ; Ovarian Neoplasms/metabolism* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred BALB C ; Mice ; Rats ; Xenograft Model Antitumor Assays ; Humans ; Cell Line, Tumor ; Antineoplastic Agents/pharmacology*

Objective:To understand the characteristics of scientific research cooperation network, research hotspots, evolution paths and development trends of advance care planning (ACP) , so as to provide reference for follow-up related research.Methods:With the theme of "advance care planning", the retrieval results based on Web of Science core collection database were respectively imported into VOS viewer and CiteSpace for visual analysis, and the retrieval time was from database construction to February 3, 2021.Results:A total of 2 456 articles meet the selection criteria. The annual publications were all less than 50 from 1993 to 2009, which showed a rapid upward trend from 2010 to now. The distribution trend of citation frequency was basically the same as that of publications. Most of the authors and institutions are European and American. Chan Helen Yue-lai of the Chinese University of Hong Kong ranked first in China and 19th in the world in terms of publicationsand Chinese scholars' research in this field is still in its infancy. Research hotspots included ACP alternative decision-making skills training, and the research frontiers and evolutionary paths included ACP, severe mental illness, alternative decision-making, life planning, end-stage renal disease, doctor's orders, ACP model, advanced dementia, chronic heart failure, etc.Conclusions:Since 2010, the number of articles published in this field and the frequency of citations have shown a rapid upward trend. The United States, Belgium, Canada and other countries have developed well in this field and Scholars of China have a wide space for development in this field. The advanced research experience reported in the foreign ACP literature can be used for reference to deepen and speed up the clinical practice research in the field of ACP in China.

Objective To discuss the safety and effectiveness of robot-assisted thyroidectomy using Da Vinci system.Methods Endoscopic thyroidectomy assisted by Da Vinci system was performed in 20 patients,including 5 cases of thyroidadenoma,4 cases of nodular goiter,and 11 cases of thyroid carcinoma.The max diameter of thyroid lump is 5.33 cm.Among 9 cases of benign thyroid neoplasm,5 cases underwent unilateral subtotal lobectomy,and 4 cases underwent unilateral near total thyroidectomy.Among 11 cases of thyroid carcinoma,7 cases underwent bilateral near total thyroidectomy,and 4 cases underwent bilateral total thyroidectomy,at the same time,all the 11 cases underwent central region lymph node dissection.Results The robot-assisted endoscopic thymidectomy was successfully carried out in 20 cases.The mean operation time was 206.4 (105～372)min.The mean operative blood loss was 27.3 ml.The draining tube was moved 3 to 6 days after surgery.The mean postoperative hospital stay was 4.9 days.The mean hospital expense was 60 172 yuan RMB.No complication occurred.20 patients were satisfied with the cosmetic effect and compararive curative effect.Conclusions The robot-assisted endoscopic thymidectomy is an efective method for thyroid diseases.The methed can get more clear vision,higher safety,and good cosmetic efect.

In order to explore the reason why hypokalemia could increase the vulnerable window (VW) for unidirectional conduction block in Long QT Syndromes (LQTS), we observed the effect of hypokalemia on the spatial gradients of Na channel conductance (G(Na)) and gating factors by using the LR91 1-dimensional heterogeneous virtual cardiac ventricular tissue model quatitively. The computer simulation experiments were divided into two groups, namely control and LQTS groups. The action potential was elicited after the basic stimulus S1 (-70 microA/microF, 1.5 ms) was given 10 times with basic cycle length (BCL) 500, 1000 and 2000 ms. To test the VW in unit of time (VWtime), the S1-S2 programmed stimuli were used with shortening S1S2 interval at the decrement of 1 ms. At the same time, the spatial gradients of Na channel conductance (G(Na)) and gating factors, m, h, j, were investigated. The APD and ionic channel currents were also detected under the conditions of normal and lower concentration of K+ outside of cell. We found that hypokalemia, LQTS and slow pacing rate enhanced the spatial gradient of G(Na) by increasing the spatial gradient of inactive gating factors h x j. The results also showed that hypokalemia deduced the peak values of I(K) and I(K1), which prolonged the action potential duration and enlarged the repolarization dispersion in this 1-D tissue cable model. Possibly these are the important factors to cause the spatial gradient of h x j and G(Na). enlargement. These changes increase the incidence of unidirectional conduction block of VW, and are vital reasons to increase the possibility of ventricular arrhythmia generation.
Computer Simulation ; Extracellular Space ; metabolism ; Humans ; Hypokalemia ; metabolism ; Long QT Syndrome ; etiology ; metabolism ; physiopathology ; Models, Biological ; Myocardium ; metabolism ; Sodium Channels ; metabolism

Objective To investigate the inhibitory effect of arsenic trioxide (As 2O 3) on the survivin expression in heterologous graft model of human breast infiltrating duct carcinoma in nude mice. Methods Nude mice bearing the transplanted tumor were randomly divided into four groups: negative control (saline), positive control (cisplatin at the dose of 1.5 mg/kg), and two experimental groups (arsenic trioxide at the doses of 1.5 mg/kg and 3.0 mg/kg). The expression of survivin mRNA and protein expressions of surviving and Caspase 3 in neoplastic tissues were detected by in situ hybridization and immunohistochemical method, respectively. Results In negative control group, the expressions of survivin mRNA and survivin protein were in moderate degree with positive rates of 82.42% and 78.85%, respectively. The positive rates of moderate degree in experimental groups 1 and 2 were gradually decreased with the increasing dose of arsenic trioxide ( P

Objective:To investigate the expression and significance of survivin in human breast infiltrating duct carcinoma.Methods:In twenty-eight samples of human breast infiltrating duct carcinoma without chemotherapy,seventeen human breast infiltrating duct carcinoma with chemotherapy,fifteen human normal breast tissue adjacent to carcinoma,twenty breast benign lesion the expressions of survivin were determined by methods of in situ hybridization and immunohistochemistry.Results:The expressions of survivin mRNA were positively correlated with that of survivin protein in every marker and showed no significant difference.The positive expressions of survivin in human breast infiltrating duct carcinoma without chemotherapy were impressively high and they were significantly different among the ages,TNM stages,pathology grades,lymph node metastases and types of receptors( P

Objective To investigate the effects of As_2O_3 on expression of NF-?B p65, survivin and caspase-3 in human breast infiltrating duct carcinoma xenograft model on nude mice. Methods A human breast infiltrating duct carcinoma model on nude mice was established and the nude mice were divided randomly into three groups: control group, DDP group and As_2O_3 group (1.5 and 3.0 mg/kg concentrations). The expression of survivin mRNA was detected with the method of in situ hybridization and the expressions of NF-?B p65, survivin and caspase-3 protein were measured with immunohistochemistry. Results The positive rates of NF-?B p65 and survivin expression were higher in the control group than those in the DDP group and the As_2O_3 groups, but that of caspase-3 was on the opposite way (P