Objective To explore the clinical effect of sustained low-efficient dialysis (SLED) combined with hemoperfusion(HP)in sepsis patients,and its protection for the kidney.Methods Sixty two patients of sepsis with acute kidney injury(AKI) were randomly divided into two groups.Based on routine treatment,control group (n =31) was treated with HP alone for 2h per day,and combined group (n =31) was treated with HP and SLED at the first 2h,and SLED for the next 10-12h.All the patients were treated for 3 days.The inflammation factors and index of renal function were detected before and after treatment,and change of haemodynamics were observed and analyzed.Results After treatment for 12,24,48h,the TNF-α,IL-6,IL-10 and Scr,BNP in both groups were all improved,while the inflammation factors in combined groups at 48h after treatment were significantly lower than those in control group,and levels of Scr and BNP at 12,24,48h after treatment were all lower than those in control group (P ＜ 0.05).There were no significant differences on the levels of CVP,MAP at 12,24,48h after treatment in combined groups (P ＞ 0.05),while these indicators were all higher than those in control group (P ＜ 0.05).Conclusion HP combined with SLED in treating sepsis with AKI can effectively remove inflammatory mediators,promote kidney function recovery and stability of hemodynamic.

Objective To investigate the protective effect of breviscapine on ischemia-reperfusion renal injury, which provides scientific theoretical basis for clinical prevention and treatment of renal ischemia-reperfusion injury. Method 36 SPF male healthy SD rats were randomly divided into 3 groups, 12 rats in each group. Group A was ischemia-reperfusion group, group B was erigeron breviscapus injection preconditioning group, and group C was sham operation group. Rats in group A and C were injected with normal saline, while rats in group B were given 12 ml/kg erigeron breviscapus injection by intraperitoneal injection., After 14 days, renal function, renal antioxidant indexes, renal cell apoptosis indexes and expression of Bcl-2, Bax in renal tissue of three groups were compared. Results The indexes of renal function showed that blood urea nitrogen (BUN) and Serum creatinine (SCr) in group B were significantly lower than group A (P<0.05), but significantly higher than group C (P<0.05). Renal antioxidant indexes showed that superoxide dismutase (SOD) and malondialdehyde (MDA) in group B were significantly higher than group A (P<0.05), but significantly lower than group C(P<0.05). The index of renal cell apoptosis showed that the apoptosis index AI in group B was significantly lower than group A (P<0.01), but significantly higher than group C (P<0.01). The results of immunohistochemical staining showed that the expression of Bcl-2 in group B were significantly higher than that of group A and group C (P<0.05), and the expression of Bax in group B was significantly lower than that in group A (P<0.05) while significantly higher than group C (P<0.01). The ratio of Bcl-2/Bax in group B was significantly higher than group A and group C (P<0.05). Conclusion Erigeron Breviscapus Injection may have a protective role on renal ischemia reperfusion injury though antioxidant and anti-apoptosis.

OBJECTIVETo study the effects of tunicamycin (a glycosylation inhibitor) combined with cisplatin on the proliferation and apoptosis of human nasopharyngeal carcinoma cells and explore the molecular mechanism.

METHODSNasopharyngeal carcinoma CNE-1 and CNE-2 cells cultured in vitro were treated with different concentrations of tunicamycin with or without cisplatin. The inhibition of cell proliferation was examined using MTT assay and colony formation assay, and the cell apoptosis was analyzed using flow cytometry with propidium iodide staining. The expressions of Bax, Bcl-2, and GRP78 in cells treated with 3 µmol/L tunicamycin with or without 6.00 µmol/L cisplatin were measured with Western blotting.

RESULTSTreatment with tunicamycin or cisplatin obviously inhibited the proliferation of CNE-1 and CNE-2 cells. Treatment with 3 µmol/L tunicamycin for 24, 36 and 48 h resulted in a viability of 72.13%, 51.97%, and 37.56% in CNE-1 cells and 85.61%, 56.95%, and 43.66% in CNE-2 cells, respectively, and the combined treatment with 6 µmol/L cisplatin lowered the cell viability to 67.97%, 47.76%, and 34.68% in CNE-1 cells and 56.89%, 37.05%, and 29.30% in CNE-2 cells, respectively. Tunicamycin at 0.3 µmol/L combined with 0.6 µmol/L cisplatin showed an obviously enhanced inhibitory effect on colony formation of CNE-1 and CNE-2 cells. Tunicamycin treatment (3 µmol/L) of CNE-1 and CNE-2 cells for 48 h induced an apoptosis rate of only 8.89% and 8.67%, but when combined with 6 µmol/L cisplatin, the cell apoptosis rate increased to 37.02% and 32.25%, significantly higher than that in cells with cisplatin treatment alone (7.25% and 6.36%, respectively). Compared with tunicamycin and cisplatin alone, the combined treatment significantly increased Bax expression and decreased Bcl-2 expression in the cells; tunicamycin up-regulated the expression of GRP-78 and enhanced the activity of caspase-3.

CONCLUSIONTunicamycin can inhibit the proliferation of CNE-1 and CNE-2 cells and enhance cisplatin-induced cell death, the mechanism of which may involve excessive endoplasmic reticulum stress response and increased activity of caspase-3.

Apoptosis ; drug effects ; Carcinoma ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Endoplasmic Reticulum Stress ; drug effects ; Heat-Shock Proteins ; metabolism ; Humans ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Tunicamycin ; pharmacology ; bcl-2-Associated X Protein ; metabolism

Objective:To investigate the efficacy of liraglutide combined with enpagliflozin in the treatment of obesity complicated by type 2 diabetes mellitus.Methods:A total of 160 obesity patients with type 2 diabetes mellitus who received treatment in Yuyao People's Hospital, China between October 2018 and October 2019 were included in this study. They were randomly assigned to receive repaglinide, insulin detemir and metformin in combination (control group, n = 80) or liraglutide, enpagliflozin and metformin in combination (treatment group, n = 80). After 3 months of treatment, fasting blood glucose, glycosylated hemoglobin, 2-hour postprandial blood glucose, body mass index, tumor necrosis factor-alpha, C-reactive protein, interleukin-6, leptin, adiponectin, and vaspin as well as the incidence of adverse reactions were compared between the control and treatment groups. Results:After treatment, fasting blood glucose, glycosylated hemoglobin, 2-hour postprandial blood glucose and body mass index were reduced in each group. They were (7.89 ± 1.02) mmol/L, (8.10 ± 1.25) %, (11.10 ± 1.59) mmol/L, (23.18 ± 2.19) kg/m 2, respectively in the observation group, which were significantly lower than those in the control group [(9.88 ± 1.27) mmol/L, (11.20 ± 1.85)%, (13.67 ± 2.01) mmol/L, (27.80 ± 2.51) kg/m 2, t1 = 10.927, t2 = 12.418, t3 = 8.969, t4 = 12.405, all P < 0.001). After treatment, tumor necrosis factor-alpha, C-reactive protein and interleukin-6 levels were reduced in each group. Their levels in the observation group were [(51.19 ± 3.19) pg/L, (2.14 ± 0.31) mg/L, (4.07 ± 0.67) pg/L, respectively, which were significantly lower than those in the control group [(62.18 ± 4.10) pg/L, (3.66 ± 0.58) mg/L, (5.96 ± 0.81) pg/L, t1 = 18.922, t2 = 20.672, t3 = 8.969, all P < 0.001). After treatment, leptin and vaspin levels were reduced in each group, and their values in the observation group were (5.48±0.94) μg/L, (1.62 ± 0.37) μg/L, respectively, which were significantly lower than those in the control group [(6.59 ± 0.82) μg/L, (1.99 ± 0.52) μg/L, t1=7.959, t2=10.323, both P < 0.001]. Adiponectin level increased in each group, and it was significantly higher in the observation group than in the control group [(7.13 ± 1.52) mg/L vs. (5.12 ± 0.85) mg/L, t3 = 5.185, P < 0.001]. There was no significant difference in the incidence of adverse reactions between control and observation groups ( χ2 = 0.313, P > 0.05). Conclusion:Liraglutide combined with enpagliflozin for the treatment of obesity complicated by type 2 diabetes mellitus is highly effective. It can effectively lower blood glucose level, reduce body mass and inflammatory reactions, further regulate serum vaspin, leptin and adiponectin levels and is highly safe. Therefore, this method can be widely used in the clinic.

Objective:To analyze the input and output status of health resources in primary medical and health institutions and their allocation efficiency in different regions of China, and to provide an empirical basis for optimizing the allocation of primary medical and health resources in China among regions.Methods:The input index data (number of beds and number of health personnel) and output index data (number of primary medical and health institutions visits, number of family health services, number of hospital admissions) of primary medical and health institutions in China in 2020 were extracted from the China Health Statistical Yearbook 2021. Based on the BCC ( Banker, Charnes, Cooper) model of data envelopment analysis ( DEA), the Bootstrap- DEA method was used to correct bias, the allocation efficiency of primary medical and health resources in 31 provinces was calculated and the regional differences were analyzed. Results:After bias correction, the technical efficiency (TE) of resource allocation in primary medical and health institutions decreased by 0.102. The average TE score of all 31 primary medical and health institutions was 0.669, indicating a serious problem of ineffective use of technology. The TE of the eastern, central and western regions was 0.694, 0.663, and 0.649 respectively. There was obvious polarization in the central regions.Further analysis of the efficiency improvement of non DEA efficient provinces showed that 2 DEA weakly efficient provinces and 16 DEA ineffective provinces had several reference provinces for efficiency configuration improvement; The provinces that have been referenced more than 10 times were Zhejiang, Chongqing, Sichuan, and Ningxia, while the provinces that were listed as the first reference by other provinces were Ningxia, Chongqing, Zhejiang, and Tibet.Conclusions:The resource allocation efficiency of primary medical and health institutions in China is relatively low, and regional differences are obvious. The balance between different inputs and outputs should be considered when allocating the resources. Non DEA effective provinces can use DEA analysis to find the most suitable reference object and make reference improvements in the short term.

OBJECTIVETo investigate the anti-cancer effect of low-molecular-weight heparin (LMWH) combined with doxorubicin and explore the mechanism.

METHODSHepatocellular cancer HepG2 cells exposed to LMWH, doxorubicin, or both were evaluated for cell viability with MTT assay and for changes in their migration ability using wound healing assay and Transwell migration assay. The changes in cellular expressions of matrix metalloproteinase-9 (MMP-9) and MMP-2 mRNA and proteins were analyzed with quantitative real-time PCR (qRT-PCR) and Western blotting, and ELISA was used to determine heparanase (HPA) concentration in the cell culture medium.

RESULTSHepG2 cells exhibited suppressed proliferation in response to LMWH and doxorubicin treatments. The combined treatment caused a significantly higher inhibition rate of cell migration than LMWH and doxorubicin alone. LMWH enhanced doxorubicin-induced down-regulation of MMP-9, MMP-2 and HPA in the cells.

CONCLUSIONSLMWH can enhance the inhibitory effect of doxorubicin on the migration of HepG2 cells, the mechanism of which may involve the down-regulation of MMP-9, MMP-2 and HPA expressions.

Cell Movement ; drug effects ; Cell Survival ; Down-Regulation ; Doxorubicin ; pharmacology ; Glucuronidase ; chemistry ; Hep G2 Cells ; Heparin, Low-Molecular-Weight ; pharmacology ; Humans ; Liver Neoplasms ; pathology ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Neoplasm Invasiveness ; RNA, Messenger ; Real-Time Polymerase Chain Reaction

Objective:To explore the effect of task-driven group workshop learning method on teaching satisfaction degree and practical ability in Mongolian medical nursing students.Methods:From September 2018 to January 2020, using convenient sampling method, a total of 38 Mongolian undergraduate nursing students of grade 2016 of Mongolian Medical College of Inner Mongolia Medical University were recruited as control group to receive traditional method, and the teaching practice activities were arranged after the main content was completed. Another 39 students of grade 2017 were recruited as observational group to receive task-driven group workshop learning method. The preparation of teaching practice tasks will run through all stages of teaching. The differences of students′ achievement, teaching satisfaction and autonomous learning ability between the two groups were compared.Results:The grade of observational group was 84.81 ± 3.45, higher than 76.16 ± 3.59 of the control group , which had significant difference ( t=-5.35, P<0.05). The score of teaching satisfaction of observational group was 82.00 ± 11.62, higher than 70.94 ± 6.65 in the control group, which had significant difference ( t=-5.10, P<0.05). The dimensions of information ability, cooperation ability and total score of the Autonomous Learning Ability Scale in observational group scored 39.28 ± 6.46, 24.54 ± 3.45, 98.13 ± 14.58, which were higher than 36.18 ± 5.46, 22.39 ± 3.59, 91.37 ± 11.47 in the control group, which had significant difference ( t=-2.27, -2.67, -2.26, all P<0.05). Conclusions:The task-driven group workshop learning method can improve the study result and the satisfaction of teaching, it can also improve the information ability and cooperation ability in Mongolian medical nursing students, which is worthy of reference in nursing teaching.

OBJECTIVE: To explore the effects of 3-methyladenine (3-MA, an autophagy inhibitor) on sensitivities of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy and the underlying mechanisms.
 METHODS: Cell proliferation was examined by MTT and colony formation assay, while cell apoptosis was evaluated by annexin V/PI double staining and 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining. Mitochondrial membrane potential was measured by commercial kit (JC-1). The expression of endoplasmic reticulum stress (ERS)-related protein, glucose-regulated protein 78 (GRP78) and autophagy-related protein beclin1, microtubule-associated protein 1 light chain 3 (LC3) were examined by Western blot.
 RESULTS: Cisplatin (DDP), ionizing radiation (IR) or tunicamycin (TM) treatment obviously inhibited the proliferation of HONE-1 cells in a concentration-dependent and time-dependent manner. Compared with control group, pretreatment with 1 mmol/L of 3-MA significantly 
reduced cell viability and enhanced the apoptosis in the DDP (6.00 μmol/L), 4.00 Gy IR or TM (1.00 μmol/L) groups. There was no significant difference in the apoptosis between the DDP (5.8%) and 4Gy IR (6.7%) groups. Compared with the control group, protein levels of GRP78, beclin1 and lipid-conjugated membrane-bound form (LC3-II) were significantly increased after the treatment of DDP, 4.00 Gy IR or TM, which were inhibited by pretreatment of 3-MA.
 CONCLUSION 3-MA can sensitize HONE-1 cells to chemotherapy and radiotherapy, which is related to prevention of endoplasmic reticulum stress-induced autophagy in nasopharyngeal carcinoma cells.
Adenine ; analogs & derivatives ; pharmacology ; Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; Beclin-1 ; Carcinoma ; Cell Line, Tumor ; drug effects ; radiation effects ; Cell Proliferation ; Cell Survival ; Cisplatin ; pharmacology ; Endoplasmic Reticulum Stress ; Heat-Shock Proteins ; metabolism ; Humans ; Membrane Potential, Mitochondrial ; Membrane Proteins ; metabolism ; Microtubule-Associated Proteins ; metabolism ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; pathology ; Radiation, Ionizing ; Radiation-Sensitizing Agents ; pharmacology ; Tunicamycin ; pharmacology

OBJECTIVETo observe the effects of 2-deoxyglucose inhibiting synovial pannus of adjuvant arthritis rats and to explore its potential mechanism of inhibiting angiogenesis by investigating proliferation, migration and matrigel tube formation assay .

METHODSThe effect of 2-DG on synovial pannus was evaluated by histopathology of HE staining; HUVEC proliferation was determined by CCK-8 method; migration of FLS were determined by transwell; matrigel tube formation assay was made for assessing tube number of HUVEC; p-AMPK and Bcl-2 were detected by Western blot assay; AMPK signaling pathway in HUVEC was inhibited by compound C, which is an inhibitor of AMPK activation.

RESULTS2-DG (200 mg/kg) obviously decreased appearance of synovial pannus ( < 0.01); , 2-DG (0.5 mmol/L and/or 5 mmol/L) obviously inhibited proliferation, migration and tube number of HUVEC ( < 0.01 or < 0.001), and its effects on HUVEC were reversed by using AMPK antagonist (Compound C); Western blot showed that 2-DG (5 mmol/L) increased expression of p-AMPK and decreased expression of Bcl-2 ( < 0.05).

CONCLUSIONSActivating AMPK pathway and decreasing expression of Bcl-2 may the potential mechanism by which 2-DG contributes to anti-angiogenesis and effects of inhibiting proliferation, migration and tube number of HUVEC.

OBJECTIVE: To investigate the effects of LCL161, a Smac mimetic, on the proliferation and apoptosis in hepatocellular carcinoma cells and the underlying mechanisms. 
 METHODS: The effect of LCL161 on the cell viability of HepG2 and SMMC7721 cells was measured by MTT assay. The effect of LCL161 at lower concentrations on the proliferation in hepatocellular carcinoma (HCC) cells was detected by colony formation assay. Apoptosis was assessed by flow cytometry with PI staining. The mitochondrial membrane potential was measured by JC-1 staining. The expression of PARP, p-Akt, cIAP1 and XIAP protein was analyzed by Western blot.
 RESULTS: LCL161 displayed notable antiproliferative activity on HCC cells at the concentrations of 1-16 μmol/L (P<0.01), with IC50 values of 4.3 and 4.9 μmol/L for HepG2 and SMMC7721 cells, respectively, after treatment for 48 h. LCL161 at lower concentrations obviously inhibited the colony formation of HCC cells. LCL161 induced significant apoptosis in HCC cells (P<0.01), and resulted in the apoptotic rate at (1.5±0.8)% or (1.8±0.6)% , (15.2±2.8)% or (12.2±2.4)%, (28.7±3.0)% or (22.4±2.7)%, (34.6±2.3)% or (30.2±2.4)% for HepG2 cells or SMMC7721 cells at the concentration of 0, 2, 4 or 8 μmol/L, respectively. The result of JC-1 staining indicated that the mitochondrial membrane potential of HCC cells was reduced by LCL161. In addition, LCL161 promoted the cleavage of PARP, down-regulated the protein expression of p-Akt, and degraded cIAP1.
 CONCLUSION LCL161 possesses significant anti-proliferative activity and pro-apoptotic action in HepG2 and SMMC7721 cells, which might be correlated with reduction in mitochondrial membrane potential, down-regulation of p-Akt and degradation of cIAP1.
Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; drug therapy ; genetics ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; Down-Regulation ; Hep G2 Cells ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Liver Neoplasms ; Membrane Potential, Mitochondrial ; drug effects ; Proto-Oncogene Proteins c-akt ; genetics ; Thiazoles ; pharmacology ; Ubiquitin-Protein Ligases ; metabolism ; X-Linked Inhibitor of Apoptosis Protein