Objective To identify the activity of HCV IRES translation differences and identify the relationship between HCV IRES translation activity and ROS in different concentrations of ferric ammonium citrate ( FAC) in-duction.Methods 1 ) Expression plasmid pCI-Rluc-HCV IRES-Fluc was confirmed by endonuclease digestion as well as luciferase transient expression in Huh-7 cell;2) Controlled by dual-luciferase reporter assay, the differ-ent translation activity of HCV internal ribosomal entry site ( IRES ) was examined in a concentration of 50 μmol/L and 300μmol/L of FAC induction;ROS fluorescent staining method was used to detect the activity of ROS in Huh-7 cells, Western blot method was used to detect the protein expression changes of Nrf2 in Huh-7 cells;3) On the basis of the above experiments, 100 μmol/L DPI was added in 300 μmol/L FAC experimental group, to analyse the changes of HCV replication and ROS production after joining DPI.Results The generation of ROS and the activity of luciferase in the model group were significantly higher than that in the control group ( P<0.05 ) .FAC can enhance the expression of HCV IRES and increase the production of ROS , then causing Nrf2 expression in Huh-7 cell.However,after adding ROS inhibitor DPI, the above functions in Huh-7 cell were weakened.Conclusions The increase of HCV IRES expression induced by FAC is related to excessive ROS pro-duction induced by FAC in Huh-7 cells.

Insomnia is a common disorder in the elderly and seriously affects life quality of the elderly.This article reviews the efficacy and safety of pharmacological agents for the treatment of insomnia in the elderly, in order to provide a reference for clinical practice.

OBJECTIVETo study the safety and effectiveness of laparoscopic radiofrequency ablation for centrally located renal tumors.

METHODSFrom January 2009 to April 2013, thirteen patients who diagnosed as centrally located renal tumors were treated with laparoscopic radiofrequency ablation in the Department of Urology of Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School. All of the cases were T1aN0M0 stage, 9 patients were male, 4 were female, the mean age was 56 years (range, 38-73 years). All tumors were unilateral, eight lesions were in the left kidney and five in the right kidney. Intraoperative real-time ultrasound and temperature probes were used to guide the range of radiofrequency ablation. Ice saline was injected through ureteral catheter for cooling the collecting system. The postoperative serum creatinine and glomerular filtration rate (GFR) data were collected,all patients were followed up with enhanced CT or MRI.The pre- and post-operative date were compared by paired t test.

RESULTSAll patients underwent laparoscopic radiofrequency ablation successfully. The mean operation time was (113±13) minutes and the mean blood loss was (99±23) ml. The mean pre- and post-operative serum creatinine was (71±11) µmol/L and (74±11) µmol/L, the mean pre- and post-operative GFR was (49±8) ml/min and (45±7) ml/min. There was no significant statistic difference between pre-operation and post-operation (t=-1.371 and 1.986, P>0.05). The mean follow-up was 37 months, range 12-63 months. No evidence of local recurrence or distant metastasis was found.

CONCLUSIONSLaparoscopic radiofrequency ablation for T1aN0M0 centrally located renal tumors could be performed safely with good outcomes. Intraoperative real-time ultrasound and temperature probes are helpful to control the range of radiofrequency ablation. Physical cooling of renal collecting system could reduce the occurrence of postoperative hydronephrosis and leakage of urine.

Adult ; Aged ; Catheter Ablation ; Female ; Glomerular Filtration Rate ; Humans ; Kidney ; Kidney Neoplasms ; therapy ; Laparoscopy ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Operative Time ; Postoperative Period ; Treatment Outcome

Objective:To investigate the risk factors for axial deviation in the treatment of tibial defect susing Orthofix unilateral external fixator and proximal tibial osteotomy for bone transport.Methods:A retrospective study was performed to analyze the clinical data of 90 patients who had been treated for tibial bone defects by the Orthofix unilateral external fixator at Department of Microrepair and Reconstruction, The First Hospital Affiliated to Xinjiang Medical University from May 2012 to June 2019. There were 77 males and 13 females with a mean age of 41.2 years (from 17 to 63 years).The bone defects ranged from 4 to 13 cm in length. According to the Paley criteria for axial deviation, the 90 patients were divided into 2 groups: a deviation-free group with no axial deviation or an axial deviation ≤5° and a deviation group with an axial deviation>5°. The 2 groups were compared in terms of age, number of prior surgery, defect length, placement angle of Schanz screws, external fixation time, external fixation index and bending degree of Schanz screws at the last follow-up.The factors with P<0.05 were analyzed by multivariate logistic regression to find the risk factors for coronal axial deviation. Results:The 90 patients were followed up for an average of 23 months (from 12 to 40 months). The incidence of axial deviation in this cohort was 36.7% (33/90).The deviation group had a significantly larger number of prior surgery [5 (3, 6) times], a significantly longer defect length [8 (8, 9) cm], a significantly longer external fixation time [400.0 (341.8, 426.3) d], and a significantly greater bending degree of Schanz screws at the last follow-up [1.2° (0.4°, 3.5°)] than the deviation-free group [3 (2, 3) times, 6 (5, 8) cm, 340.8 (226.5, 422.8) d, and 0.8° (0.2°, 3.7°)] (all P<0.05). Multivariate logistic regression analysis showed that the number of prior surgery ( OR=2.581, 95% CI: 1.496-4.450, P=0.001) and the defect length ( OR=5.310, 95% CI: 1.952-14.442, P=0.001) were the risk factors for the axial deviation. Conclusion:In the treatment of tibial defect susing Orthofix unilateral external fixator and proximal tibial osteotomy for bone transport, the more prior surgeries and the longer a bone defect, the higher the risk for axial deviation.

OBJECTIVE To explore the effect and potential mechanism of the compatibility of Astragali Radix-Puerariae Lobatae Radix on ferroptosis of liver cells in type 2 diabetes mellitus （T2DM） insulin resistance （IR） rats. METHODS Sixty male SD rats were randomly divided into control group （12 rats） and modeling group （48 rats）. The modeling group was fed with a high- fat diet for 4 consecutive weeks and then given a one-time tail vein injection of 1% streptozotocin to establish T2DM IR model. The model rats were randomly divided into model group， the compatibility of Astragali Radix-Puerariae Lobatae Radix group [QG group， 4.05 g/（kg·d）， intragastric administration]， ferroptosis inhibitor ferrostatin-1 group [Fer-1 group， 5 mg/kg by intraperitoneal injection， once every other day]， the compatibility of Astragali Radix-Puerariae Lobatae Radix+ferroptosis inducer erastin group [QG+erastin group， 4.05 g/（kg·d） by intragastric administration+erastin 10 mg/（kg·d）， intraperitoneal injection]. After 4 weeks of intervention， serum fasting blood glucose （FBG） and fasting insulin （FINS） were measured in each group of rats， and homeostasis model assessment of insulin resistance （HOMA-IR） and the natural logarithm of insulin action index（IAI） were calculated； the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate transaminase （AST） and alanine transaminase （ALT）， Fe2+ and Fe content， glutathione （GSH）， malondialdehyde （MDA） and superoxide dismutase （SOD） levels， NADP+/NADPH ratio and reactive oxygen species （ROS） were determined. The pathological morphology of its liver tissue was observed； the protein expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， long-chain acyl-CoA synthetase 3 （ACSL3）， ACSL4， ferritin mitochondrial （FTMT）， and cystine/glutamate anti-porter （xCT） in the liver tissue of rats were detected. RESULTS Compared with control group， the liver cells in the model group of rats showed disordered arrangement， swelling， deepened nuclear staining， and more infiltration of inflammatory cells， as well as a large number of hepatocyte vacuoles and steatosis； FBG （after medication）， the levels of TC， TG， LDL-C， AST， ALT， FINS， MDA and ROS， HOMA-IR， Fe2+ and Fe content， NADP+/NADPH ratio and protein expression of ACSL4 were significantly increased or up-regulated， while the levels of HDL-C， GSH and SOD， IAI， protein expressions of GPX4， FTH1， ACSL3， FTMT and xCT were significantly reduced or down-regulated （P＜0.01）. Compared with the model group， both QG group and Fer-1 group showed varying degrees of improvement in pathological damage of liver tissue and the levels of the above indicators， the differences in the changes of most indicators were statistically significant （P＜0.01 or P＜0.05）. Compared with QG group， the improvement of the above indexes of QG+erastin group had been reversed significantly （P＜0.01）. CONCLUSIONS The compatibility decoction of Astragali Radix-Puerariae Lobatae Radix can reduce the level of FBG in T2DM IR rats， and alleviate IR degree， ion overload and pathological damage of liver tissue. The above effects are related to the inhibition of ferroptosis.

In this report, a series of novel piperidine-substituted thiophene[3,2-]pyrimidine derivatives were designed to explore the hydrophobic channel of the non-nucleoside reverse transcriptase inhibitors binding pocket (NNIBP) by incorporating an aromatic moiety to the left wing of the lead . The newly synthesized compounds were evaluated for anti-HIV potency in MT-4 cells and inhibitory activity to HIV-1 reverse transcriptase (RT). Most of the synthesized compounds exhibited broad-spectrum activity toward wild-type and a wide range of HIV-1 strains carrying single non-nucleoside reverse transcriptase inhibitors (NNRTI)-resistant mutations. Especially, compound exhibited the most potent activity against wild-type and a panel of single mutations (L100I, K103N, Y181C, Y188L and E138K) with an EC ranging from 6.02 to 23.9 nmol/L, which were comparable to those of etravirine (ETR). Moreover, the RT inhibition activity, preliminary structure-activity relationship and molecular docking were also investigated. Furthermore, exhibited favorable pharmacokinetics (PK) profiles and with a bioavailability of 33.8%. Taken together, the results could provide valuable insights for further optimization and compound holds great promise as a potential drug candidate for the treatment of HIV-1 infection.