OBJECTIVE: To investigate the effects of bortezomib (BTZ) combined with polyphyllin Ⅶ (PP7) on proliferation, apoptosis and oxidative stress of myeloma cell line ARH-77. METHODS: MTT assay was used to detect the inhibitory effects of different concentrations of BTZ, PP7 monotherapy, and their combination on the proliferation of ARH-77 cells. In subsequent experiments, the cells were divided into 4 groups: control group (no drug added), BTZ (15 nmol/L) group, PP7 (1.5 μmol/L) group and BTZ(15 nmol/L)+PP7 (1.5 μmol/L) group. The effects of the two drugs on the morphology of ARH-77 cells were observed. Flow cytometry was used to detect the apoptosis rate of the cells in each group. Calcein-AM/PI double staining kit was used to observe the status of the cells and the cell viability were evaluated. The expression of apoptosis-related proteins were detected by Western blot. DCFH-DA fluorescent probe was used to detect the levels of reactive oxygen species (ROS). RESULTS: Both BTZ and PP7 monotherapy, as well as their combination, could inhibit the growth of ARH-77 cells in a dose-dependent manner (r_BTZ=-0.9717, r_PP7=-0.9941, r_BTZ+PP7=-0.9951), and the combination of BTZ and PP7 exhibited a synergistic effect within a certain concentration range. Compared with the BTZ group and PP7 group, the apoptosis rate of the BTZ+PP7 group was significantly increased (P < 0.01), the expressions of pro-apoptotic proteins Bax, Smac and P53 were significantly upregulated (P < 0.05), the expression of anti-apoptotic protein Bcl-2 was significantly downregulated (P < 0.01), and the ratio of Bax/Bcl-2 was significantly increased (P < 0.01). Compared with the control group, the level of ROS in the BTZ, PP7 monotherapy group and BTZ+PP7 group were significantly increased (P < 0.05). CONCLUSION BTZ combined with PP7 can inhibit the proliferation and induce apoptosis of ARH-77 cells, and increase the level of intracellular ROS.
Apoptosis/drug effects* ; Bortezomib ; Humans ; Cell Proliferation/drug effects* ; Oxidative Stress/drug effects* ; Multiple Myeloma/metabolism* ; Cell Line, Tumor ; Saponins/pharmacology*

Objective To analyze the chemical components of Xiaoshi Lidan pills by using UPLC-MS/MS and explore the mechanism of Xiaoshi Lidan pills in the treatment of cholelithiasis through network pharmacology and molecular docking techniques.Methods The pharmacologically active components of Xiaoshi Lidan pills were analyzed through UPLC-MS/MS and compared with standard references.Potential targets of these components were obtained by searching the TCMSP and ETCM databases,and disease-related targets for cholelithiasis were identified using the DisGeNET database.The overlapping targets were used to construct a protein-protein interaction(PPI)network in the String database,and a"drug-component-target"network was built using Cytoscape 3.9.1.GO and KEGG enrichment analyses were performed for the core targets.Finally,the top 5 compounds with strong activity were selected as ligands for molecular docking with the screened disease target genes.The anti-inflammatory activity was verified by RAW264.7 cells,and the mRNA expression of TNF-a and other inflammatory factors was detected by RT-PCR.Results UPLC-MS/MS identified 30 compounds in Xiaoshi Lidan pills,among which baicalin,quercetin,wogonin,baicalein-7-O-glucuronide,and emodin were identified as key components of Xiaoshi Lidan pills.Network pharmacology identified 107 targets associated with cholelithiasis,with Alb,TP53,ESR1,TNF,and INS identified as core targets.GO analysis indicated the involvement in inflammation response and steroid binding,while KEGG pathways were primarily related to lipid metabolism,atherosclerosis,and the TNF signaling pathway.Molecular docking analysis and anti-inflammatory screening in vitro showed that Xiaoshi Lidan pills exhibited certain anti-inflammatory activity by regulating inflammatory factors such as TNF and inhibiting NO production through baicalein,quercetin,emodin and other components.Conclusion Xiaoshi Lidan pills exerts its therapeutic effect on cholelithiasis by regulating TNF-related pathways through components such as baicalin,thereby inhibiting the inflammatory response.

Objective To systematically review the efficacy of different artificial liver support systems in the treatment of acute-on-chronic liver failure (ACLF) using a network Meta-analysis. Methods PubMed, Embase, the Cochrane library, Clinical Trial, CNKI, SinoMed, and Wanfang Data were searched for randomized controlled trials (RCTs) on different artificial liver support systems in the treatment of ACLF. Literature screening, data extraction, and method ological quality assessment were performed according to inclusion and exclusion criteria, and Stata15.1 software and R4.1.0 software were used to perform a network Meta-analysis. Results A total of 14 RCTs were included, with 1141 patients in total. The network meta-analysis showed different intervention methods had no significant difference in reducing mortality rate based on cross comparison (all P > 0.05). The probability ranking diagram showed that plasma exchange (PE) showed the best effect in reducing 30-day mortality rate, followed by extracorporeal liver assist device (ELAD), fractionated plasma separation and adsorption with Prometheus system, molecular adsorbent recirculating system (MARS), Biologic-DT liver dialysis device, and PE+MARS. PE showed the best effect in reducing 90-day mortality rate, followed by Prometheus, ELAD, and MARS. Biologic-DT showed the best effect in improving hepatic encephalopathy, followed by MARS, PE+MARS, and ELAD. Patients undergoing ELAD had the lowest risk of bleeding, and compared with standard medical treatment, Biologic-DT might increase the risk of bleeding [risk ratio=1.9×10 8 , 95% confidence interval: (4.6-6.2)×10 27 ]. Conclusion PE might be the best option for reducing 30- and 90-day mortality rates in ACLF patients. Biologic-DT has a better effect in improving hepatic encephalopathy, but it may increase the risk of bleeding.

Objective To investigate the effect and mechanism of salvianolic acid B(SalB)on myocardial fibrosis in diabetic rats based on RhoA/ROCK1 signaling pathway.Methods Diabetic rat model was established by injecting streptozotocin into tail vein of healthy male SD rats.At the end of the 12th week, the collagen fiber expression in the left ventricular myocardium of rats was detected by Sirius Red reagent staining.The protein expressions of α-SMA, Collagen and Collagen III in left ventricular myocardium were detected by Western blot.Cardiac fibroblasts(CFs)were cultured in SD rats by differential adhesion, and CFs were pretreated with different concentrations of SalB(12.5, 25, 50 μmol·L-1)for 1 h, and the optimal dose was determined by high glucose induction.RhoA protein expression in CFs was detected by immunofluorescence; the protein expressions of α-SMA, Collagen , Collagen III, RhoA and ROCK1 in CFs were detected by Western blot.Results Compared with the normal control group, the expression of collagen in left ventricular myocardium of diabetic rats increased significantly, and the expression of α-SMA, Collagen and Collagen III increased significantly.After SalB intervention, the expression of collagen decreased significantly, and the expression of the above proteins decreased significantly(P<0.01).The expression of α-SMA, Collagen , Collagen III, RhoA and ROCK1 in CFs stimulated with 25 mmol·L-1 high glucose for 24 h was significantly increased.After pretreatment with SalB(25 μmol·L-1)and inhibitor Y-27632(10 μmol·L-1), the activity of CFs was significantly inhibited, and the expression of these proteins was significantly decreased(P<0.01).Conclusion SalB can improve myocardial fibrosis in diabetic rats, and has a certain role in protecting the myocardium of diabetic rats.The mechanism may be related to the inhibition of RhoA/ROCK1 signaling pathway.

Aim To study the protective effect of simvastatin(Sim)on liver function injury in apolipoprotein E gene knockout(ApoE KO)mice fed with high-fat diet and the underlying mechanism.Methods Twenty-four 8-week-old male ApoE KO mice were randomly divided into ApoE KO group,ApoE KO+Sim group and ApoE KO+PD150606 group.The contents of total cholesterol(TC)and triglyceride(TG)in serum and liver,and the activities of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)in serum were measured.The contents of malondialdehyde(MDA)and reactive oxygen species(ROS)and the activity of superoxide dismutase(SOD)in liver were determined.The contents of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)and the activity of calpain in liver were examined.Results Compared with C57 group,ApoE KO group showed significant increase in the contents of TC and TG in both serum and liver.In addition,the activities of AST and ALT in serum and the contents of MDA and ROS in liver significantly increased,while SOD activity in liver decreased in ApoE KO group.The contents of TNF-α and IL-6 and the activity of calpain in liver significantly increased.Compared with ApoE KO group,Sim group had no significant effects on TC and TG,while reduced the activities of AST and ALT,decreased the contents of MDA and ROS,increased the activity of SOD and decreased the contents of TNF-α and IL-6 as well as the activity of calpain in liver.PD,the calpain inhibitor,had the similar effects with Sim regarding the above mentioned parameters.Conclusions Sim improved the liver function injury of ApoE KO mice,which might be related to the inhibition of calpain activity,subsequently increasing the antioxidant capacity and reducing the inflammatory response.

Lhermitte-Duclos disease (LDD) is a type of rare brain tumor located in posterior fossa. A patient with LDD located in the left cerebellum and vermis was admitted by the Department of Neurosurgery, Xiangya Hospital, Central South University. MRI scan showed slightly heterogeneous enhancement at the region close to vermis. The patient underwent partial resection on August 11, 2016 without postoperative chemoradiotherapy. The progress free survival was 11 months and the overall survival was 17 months. What the case reveals is that the partial resection is not beneficial to these patients with LDD as the residual lesion probably recurs in a short term after operation. The pathogenesis, diagnosis and treatment of LDD are explored and summarized in combination with relevant literature.
Cerebellar Neoplasms/surgery* ; Cerebellum ; Hamartoma Syndrome, Multiple/diagnostic imaging* ; Humans ; Magnetic Resonance Imaging ; Neoplasm Recurrence, Local

Objective To screen and identify the hub genes closely related to cardiac hypertrophy by using bioinformaticsmethod and biological experiments. Methods The chip data related to cardiac hypertrophy in mice were downloaded from the Gene Expression Omnibus (GEO) database, and the GE02R online tool was adopted to screen for differentially expressed genes; DAVID 6.7, String 11.0 and Cytoscape 3.7. 0 softwares were used to analyze differentially expressed genes; Kunming mice were randomly divided into a normal saline group (n = 6) and an angiotensin II (Ang II) group (n = 6) to establish a cardiac hypertrophy model, the expression of hub gene in Kunming mouse model of cardiac hypertrophy induced by Ang II was detected by Real-time PCR method. Results A total of 202 common differentially expressed genes and 12 hub genes were selected; the Real-time PCR result demonstrated that decorin(Dcn), HADHA and heat shock protein (HSP) 90αA 1 were significantly down-regulated in the Angli group. Conclusion The selected hub genes can influence the development of cardiac hypertrophy in Kunming mice through extracellular matrix and transforming growth factor β(TGF-β).

Objective To evaluate left ventriclular systolic function in patients with obstructive hypertrophic cardiomyopathy (HOCM) after modified Morrow surgery using two-dimensional speckle tracking imaging (2D-STI).Methods Twenty three HOCM patients were recruited in this study.Echocardiographic data from HOCM patients during pre-operation,1-month and 3-month post-operation were analyzed by Qlab software to compare the variation in systolic function indicators 1-month and 3-month post-operation including global and 16 segmental longitudinal strain,circumferential strain and conventional echocardiographic parameters of left ventricle.Results Compared with preoperative data of HOCM patients,postoperative LVOT diameter and pressure gradient,left atrial diameter and volume index were significantly decreased(P<0.05),but there was no significant difference in left ventricular ejection fraction(P<0.05).Compared with the preoperative case,global and segmental longitudinal strain showed significant reduction after 1 week and gradually recovered after 3 months,without significant variation.The longitudinal strain of the anteroseptum reduced significantly and the longitudinal strain of the free wall increased after 3 months,however,the circumferential strain reduced significantly.The circumferential strain of basal and middle segment after 3 months had improved significantly than those of postoperative 1 week.The circumferential strain of surgical site is no obvious change and the strain of free wall was improved after 3 months.Conclusions 2D-STI can effectively evaluate global and regional systolic function of left ventricle for HOCM patients after modified Morrow surgery.

The study is designed to evaluate the protective effect of xanthan gum (XG) injection on cartilage injury in the rabbit osteoarthritis (OA) model induced by anterior cruciate ligament transection (ACLT), and to explore the effect of XG on the expression of caspase-3 and Bax protein in OA cartilage. Sixty male New Zealand white rabbits were randomly divided into 6 groups (n=10) according to random number table method, and one group was selected randomly as the normal control group (control) while the other 5 groups of right knee were used to establish the OA model with ACLT, which were then divided into model group (model), XG-0.6 mg·kg^-1, XG-1.2 mg·kg^-1, XG-2.4 mg·kg^-1 treatment group and sodium hyaluronate (SH-1.2 mg·kg^-1) treatment group according to drug intervention. The knee joint temperature and knee joint width of each group were measured in the course of treatment. After treatment, the macroscopic morphology of rabbit joints in each group was observed. The pathological morphology of articular cartilage of rabbits in each group was observed using HE staining. The expression of Bax and cleaved caspase-3 in the cartilage of rabbits were detected by Western blot. The result shows that XG inhibited the increase in knee joint temperature and knee width caused by OA in a dose-dependent manner. XG improved the morphological abnormalities and tissue injuries of the femoral condyle and tibial plateau caused by OA. Western blot result shows that, compared with the control group, the levels of Bax and cleaved caspase-3 in knee cartilage cells of model group and XG-0.6 mg·kg^-1 group were significantly increased (P<0.01). However, no significant difference was observed in the levels of Bax and cleaved caspase-3 between the model group and the XG-0.6 mg·kg^-1 group (P>0.05). These two groups are significantly higher than those of XG-1.2 mg·kg^-1 and XG-2.4 mg·kg^-1 (P<0.01) groups. Meanwhile, no significant difference was observed in the level of cleaved caspase-3 between the knee cartilage in XG-2.4 mg·kg^-1 and XG-1.2 mg·kg^-1 group (P>0.05). The level of Bax in knee cartilage in XG-2.4 mg·kg^-1 group was lower than that of XG-1.2 mg·kg^-1 group (P<0.05). In conclusion, XG effectively protected cartilage damage in OA, and inhibited the expression of Bax and caspase-3 protein in OA cartilage.

BACKGROUNDEpilepsy is one of the most common serious neurological disorders. The present study aimed to investigate the influence of occupational status on the quality of life of Chinese adult patients with epilepsy.

METHODSThis study surveyed 819 subjects clinically diagnosed with epilepsy for more than 1 year in 11 hospitals in Beijing; 586 were employed (71.55%). All subjects completed the case report form with inquiries on demographic data, social factors, and illness. The patients' quality of life was assessed using the quality of life in patients with epilepsy-31 items (QOLIE-31) questionnaire.

RESULTSThe QOLIE-31 score in the employed group was significantly higher than that in the unemployed group. Furthermore, the scores in all the sections (overall quality of life, energy/fatigue, emotional well-being, seizure worry, cognition, social function, and medication effects) of the employed group were higher than those of the unemployed group. Both the employed and unemployed groups achieved the highest difference in social function. The QOLIE-31 score of students was higher than those of farmers and workers. Both the students and workers scored higher in the quality of life compared with the adult peasants living with epilepsy. The students and farmers showed significant differences in QOLIE-31 score, cognition, emotional well-being, overall quality of life, energy/fatigue, and social function. In contrast, no significant difference was noted in seizure worry and medication effects across the three different kinds of occupation.

CONCLUSIONOccupational status might affect the quality of life of Chinese adult patients with epilepsy, and social function is the most important contributing factor.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Employment ; Epilepsy ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Quality of Life ; Surveys and Questionnaires ; Young Adult