AIM: To investigate the blocking effects of sodium ferulate (SF) on the nonenzymatic glycation and oxidation in kidneys of diabetic rats. METHODS: The diabetic rats induced by streptozotocin (STZ) were treated with SF (110 mg/kg) per day for 8 weeks. The renal weight/body weight, clearance rate of creatinine (Ccr), proteinuria, advanced glycation end products (AGEs) in renal cortex, and the malonyldialdehyde (MDA), fructosamine (FMN), antioxidant enzymes in serum and renal cortex were measured. The pathologic changes of kidneys were also observed. RESULTS: The levels of Ccr, proteinuria, FMN and AGEs in renal cortex, FMN in serum, and renal weight/body weight in diabetic group were significantly higher than those in normal control group. In the diabetic group, there was a highter level of MDA and a lower activity of superoxide dismutase (SOD) and catalase (CAT) in serum and renal cortex than those in normal control group. Except for FMN in renal cortex, the abnormalities were significantly ameliorated in the treatment group. The pathologic changes was significant in the diabetic group, which was significantly ameliorated with the treatment of SF. CONCLUSIONS: SF protects the activity of antioxidant enzymes, clears away oxygen radicals and inhibits the deposit of AGEs in kindey, which may be the mechanisms of protecting effects of SF on kindey in diabetic rats. [

Objective To investigate the relationship among p38 mitogen-activated protein kinase (p38MAPK), NF-KB and monocyte chemoattractant protein-1 (MCP-1), and to study the role of p38MAPK, NF-κB and MCP-1 in diabetic nephropathy. Methods Protein expressions of p38MAPK and NF-κB, and mRNA expression of MCP-1 were initially investigated in rat mesangial cell line HBZY-1, which were incubated separately with 25mmol/L glucose, 100nmol/L insulin, 100 μmol/L H2 O2 and 100mg/L advanced glycosylation end products (AGEs). The relationship among p38MAPK, NF-κB and MCP-1 expression Was observed by usingSB203580, a specific inhibitor of p38MAPK. Results The expressions of p38MAPK, NF-κB and MCP-1 were increased in HBZY-1 cells incubated separately with 25mmol/L glucose, 100nmol/L insulin, 100μmol/L H2 O2and 100 mg/L AGEs. Expressions of NF-κB and MCP-1 were significantly reduced when p38MAPK was inhibited by SB203580. Conclusion p38MAPK, NF-κB and MCP-1 are involved in development of diabetic nephropathy, and p38MAPK stimulation is essential for the expressions of NF-κB and MCP-1.

The expression of cyclooxygenase-2 (COX-2) mRNA and protein was significantly increased in rat glomerular mesangial cells (RCMC) treated separately with high glucose, high insulin, H2 O2 and advanced glycosylation end products. The expressions of COX-2 mRNA and protein in RCMC induced by above 4 factors were distinctly inhibited by sodium selenite, suggesting that sodium selenite might play a significant role in the prevention of diabetic nephropathy via this mechanism.

Objective To investigate the relationship between p38MAPK and PPAR-?,and to study the role of p38MAPK and PPAR-? for diabetic nephropathy. Methods The expression of p38MAPK protein and PPAR-? mRNA was investigated in rat mesangial cells line HBZY-1 that was incubated respectively with 25 mmol/L glucose,100 nmol/L insulin,100 ?mol/L H_2O_2 and 100 mg/L AGEs. The relationship between p38MAPK and PPAR-? expression was studied by using SB203580,a specific inhibitor of p38MAPK. Results p38MAPK had significantly higher expression,while the expression of PPAR-? was significantly decreased in rat mesangial cells line HBZY-1 incubated with 25 mmol/L glucose,100 nmol/L insulin,100 ?mol/L H_ 2 O_ 2 and 100 mg/L AGEs respectively. PPAR-? activity was significantly reduced when p38MAPK was inhibited by SB203580. Conclusion p38MAPK is involved in development of diabetic nephropathy and may antagonize the expression of PPAR-?. PPAR-? activity might protect the function of kidney.

Objective To assess the quality of international studies on using aldosterone to renin activity ratio (ARR) to diagnose primary aldesteronism. Methods We searched the Cachrane Library (1962-2007.12), PubMed(1970-2007.12) ,VIP(1989-2007.12) ,Wan Fang database(1982-2007.12) ,CBMdisc(1978 -2007.12) systematically. Language was limited to Chinese and English. The Quality Assessment of Diagnostic Accuracy Studies(QUADAS) was used to assess the quality of induced diagnostic studies by two reviewers inde-pendently. Results Fourteen studies were included and assessed. We found that most of the studies were not met with QUADAS items. Nine studies didn't chose correct cases that included miscellaneous cases and confused ca-ses. Eight studies didn't describe internalized or exclusive references clearly. The gold standard in three studies could not discriminate whether the diagnosis of patients was confirmed or not. Thirteen studies did not use blind trial to compare the diagnostic test and the gold standard. Conclusions The studies using ARR to diagnose pri-mary aldesteronism should be improved in patients selection, the gold standard selection, comparison of blind trial and bias control.

Objective To evaluate the safety and efficacy of lenalidomide plus rituximab in treatment of the patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL). Methods The clinical data of the patients with relapsed/refractory B-NHL after the varieties of treatment methods in Peking Union Medical College Hospital between January 2015 and December 2017 were retrospectively analyzed. All the patients were treated with R2 regimen: oral lenalidomide (25 mg/d for day 1-day 21) and rituximab (375 mg/m2 of intravenous infusion on day 1, 28-day of each cycle); the efficacy was evaluated after three cycles. After this induction phase, the patients achieving complete response (CR), partial response (PR), or stable disease (SD) were given R2 regimen until the end of 8 cycles. The major end point was overall response rate (ORR) defined as CR + PR. Secondary end point included 1-year progression free survival (PFS), 1-year overall survival (OS) and grade 3-4 adverse events. T cell and B cell subsets of 7 patients at baseline were measured, and T cell and B cell subsets of 13 patients with good efficacy were dynamically observed. Results A total of 49 patients who received 1-4 chemotherapy regimens were included. The ORR after the R2 treatment for 3 courses was 65% (32/49). Thirty-six patients (9 cases of CR, 22 cases of PR, 5 cases of SD) were enrolled in R2 maintenance treatment. The median follow-up time was 13 months, 1-year PFS rate was 61% and 1-year OS rate was 84% . The most common adverse event was bone marrow suppression, including grade 3-4 neutropenia (27% ), grade 3-4 thrombocytopenia (6% ) and grade 4 anemia (4% ), most of which could be controlled by prolonging interval cycles or reduced lenalidomide dosage. The decreased number of CD19+B cell after treatment could be seen in 13 patients who obtained good efficacy under the dynamic observation. Conclusion Lenalidomide plus rituximab is well tolerated and highly active in the treatment of relapsed/refractory B-NHL.

A 43-year-old female patient was admitted with recurrent thrombosis for more than 2 years and thrombocytopenia for more than 1 year. Both arterial and venous thromboses developed especially at rare sites even during anticoagulation therapy such as cerebral venous sinus thrombosis. Antinuclear antibody, anti-ENA antibody and antiphospholipid antibody were all negative. Platelet count elevated to normal after high dose glucocorticoid and intravenous immunoglobulin (IVIG). Immune thrombocytopenia was suspected. When 4 grade thrombocytopenia recurred, intravenous heparin, rituximab 600 mg, IVIG and eltrombopag were administrated. After 3 weeks, thrombocytopenia did not improve, and new thrombosis developed instead. Screening of thrombophilia related genes revealed PROS1 gene heterozygous mutation and MTHFR TT genotype. Low amount of serum IgG κ monoclonal protein was detected. Heparin-induced thrombocytopenia was differentiated and excluded. Finally, serum negative antiphospholipid syndrome was considered the most likely diagnosis. Dexamethasone 20 mg/day × 4 days combined with sirolimus 2 mg/day was prescribed. The patient was discharged with low molecular weight heparin. At one month, her headache was greatly relieved. The platelet count raised to 20-30×10 9/L, and no new thrombosis or bleeding was reported.

Due to the special physiological and pathological characteristics of gliomas, most therapeutic drugs are prevented from entering the brain. To improve the poor prognosis of existing therapies, researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy. Although these strategies can be used clinically to overcome the blood‒brain barrier (BBB), the accurate delivery of drugs to the glioma lesions cannot be ensured. Nano-drug delivery systems (NDDS) have been widely used for precise drug delivery. In recent years, researchers have gathered their wisdom to overcome barriers, so many well-designed NDDS have performed prominently in preclinical studies. These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions, drug release in response to the glioma microenvironment, biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein, and carriers created according to the active ingredients of traditional Chinese medicines. We reviewed these well-designed NDDS in detail. Furthermore, we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy, and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Objective: To evaluate the efficacy and safety of maintenance therapy with reduced dose of rhTPO in the patients with primary immune thrombocytopenia (ITP) who attained stable platelet (PLT) counts after daily administration of rhTPO. Methods: Treatment was started with a daily administration of rhTPO (300 U/kg) for 2 consecutive weeks. Patients who attained stable PLT≥50×10⁹/L were enrolled to maintenance therapy starting with every other day administration of rhTPO, then adjusted dose interval to maintain platelet count (30-100) ×10⁹/L. Results: A total of 91 eligible patients were enrolled. Fourteen patients discontinued the study due to noncompliance (12/14) and investigator decision (2/14) . Among 77 patients who completed the study, 38 patients with the administration of rhTPO at every other day or less could maintain PLT≥30×10⁹/L for 12 weeks. The percentage of patients with a platelet response (PLT≥30×10⁹/L) at 4^th week, 8^th week and 12^th week of maintain therapy was 92.6% (63/68) , 82.7% (43/52) and 85.0% (34/40) , respectively. Median platelet counts remained in the range of (70-124) ×10⁹/L. The overall incidence of rhTPO-related adverse events was 7.7%. All the adverse events were generally mild. Conclusion Extending the dose interval of rhTPO is feasible to maintain stable platelet count in the patients with ITP, but the optimal dose interval is uncertain and might vary with individuals.