Tauopathies, including Alzheimer's disease (AD), are a series of neurodegenerative diseases characterized by pathological accumulation of the microtubule-associated protein tau. Since the abnormal modification and deposition of tau in nerve cells are crucial for tauopathy etiology, methods for reducing tau levels, such as promoting tau degradation, may become effective strategies for disease treatment. Herein, we identified that sorafenib significantly reduced total tau and phosphorylated tau levels through screening FDA-approved drugs. We showed that sorafenib treatment attenuated cognitive deficits and tau pathologies in PS19 tauopathy model mice. Mechanistically, we found that sorafenib inhibited multiple kinases involved in tau phosphorylation and promoted autophagy. Importantly, we further demonstrated that sorafenib also promoted the expression of the E3 ubiquitin ligase FBXW7, which could bind tau and mediate tau degradation through the ubiquitin-proteasome pathway. Finally, we showed that FBXW7 expression decreased in the brains of AD patients and tauopathy model mice, and that overexpression of FBXW7 in the hippocampus attenuated cognitive deficits and tau pathologies in PS19 mice. These results suggest that sorafenib may be a promising treatment option for tauopathies by promoting tau degradation and reducing tau phosphorylation, and that targeting FBXW7 could also serve as an alternative therapeutic strategy for tauopathies.

Mutations in the triggering receptor expressed in myeloid 2 (TREM2) gene have recently been found to be closely related to the development of Alzheimer's disease (AD) and other neurodegenerative diseases. However, the detailed mechanism underlying TREM2's participation in the pathogenesis of AD and other diseases has yet to be fully elucidated. In this review, we discuss current understanding on the structure and function of TREM2, the relevance between TREM2 and AD, and the possible causes of AD by TREM2 mutations.

Objective To study the clinical value of retroperitoneoscope-assisted intraperitoneal approach in the treatment of large renal tumors.Methods A total of 89 patients with large renal tumors (d ＞7 cm) were involved from January 2014 to December 2017.Among them,32 cases were treated by retroperitoneoscope-assisted intraperitoneal approach (group A),including 18 males and 14 females,aged (63.5±7.5)years,with 20 cases on the left and 12 on the right,and mean tumor diameter of (7.9 ± 0.6).Thirty cases were treated by laparoscopy (group B),including 17 males and 13 females,aged (64.5 ±7.3)years,with 16 cases on the left and 14 cases on the right,and the average tumor diameter of (7.6 ±0.7) cm.Twenty-seven cases underwent open surgery (C group),including 15 males and 12 females,aged (64.9 ±5.7) years,with 13 cases on the left side and 14 cases on the right,and the average tumor diameter of (7.9 ±0.6) cm.There was no statistically significant difference among the three groups in term of demographics (P ＞ 0.05).The clinical data was collected and statistical analysis was made for comparison among the three groups,including operation time,blood loss,surgical complications,postoperative intestinal recovery and postoperative hospital stay.All the patients were with single renal tumor,and no other major comorbidities were found.Results All of the 89 surgeries were successful.Hypercapnia was found in 2 cases (6.3％) in Group A,and recoverd 15 minutes after stopping pneumoperitoneum and anesthesia.The operation time was 120-200 minutes with an average of (155.0 ± 22.1) minutes.The average amount of bleeding was (141.6 ± 33.8) ml.Bowel recovered 3 (3-5) days after operation.The patients were hospitalized for 7 (7-9) days.In group B,hypercapnia was found in 2 patients (6.7％) and recoverd after stopping pneumoperitoneum and anesthesia.The time of operation was (184.2 ± 20.6) min,the amount of bleeding was (191.5 ± 46.2) ml,the bowel recovered 4 (4-6) days after operation,and the postoperative hospitalization duration was 7.5 (6-9) days.The operation time of group C was (54.0 ± 16.6) min,blood loss was (309.6 ± 50.2) ml,postoperative intestinal recovery was 5 (4-6)days,and the postoperative hospitalization time was 8 (7-12)days.Group A had less operation time than Group B(P ＜0.05),and no difference with Group C(P ＞0.05).Group A had advantages in term of blood loss and postoperative intestinal recovery time compared with B and C (P ＜ 0.05).Groups A and B had no difference in term of surgical complications and postoperative hospital stay (P ＞ 0.05),but both of the two groups had obvious advantages over group C (P ＜ 0.05).Conclusions Retroperitoneoscopeassisted intraperitoneal approach is the synergetic application of two endoscopic approaches,which is superior to any single operation for the treatment of large renal tumor,such as less bleeding,shorter operation time,faster postoperative recovery,and so on.This method not only reduces the difficulty of operation,provides an alternative for laparoscopic treatment of large renal tumors,but also has a good application for complex renal tumors complicated with renal vein and inferior vena cava tumor thrombus.

ObjectiveTo encourage development of county-level hospitals by building a performance appraisal indicator system for such institutions. Methods Using the PATH model ( a performance appraisal tool for hospital ) quality improvement, an appraisal system was built for such institutions. Centering on patients, this system encompassed such dimensions as public benefits, quality of care and safety, staff and hospital development. Results This system consisted of six level-1 indicators, 21 level-2 indicators and 70 level-3 indicators, each given due weight. Conclusions This indicator system centers on patients, follows guidance of public benefits, and aims at continuous quality improvement, making it an effective in evaluating hospital performance and providing reference for the decision-makers to promote and adjust medical reform policies.

Objective To analyze the influencing factors for doctors' prescription of essential medicines at county hospitals of Anhui province.Methods Multi-stage random sampling method was designed to conduct an investigation for doctors at nine county hospitals in Anhui province,and SPSS 1 6.0 was used to conduct descriptive statistical,chi-square test and binary logistic regression.Results 50.8% respondents reported that they had prescribed essential medicines with the rate of less than 60%. The factors of doctors'prescription for essential medicines are work experience,average monthly income, policy awareness, recognition, training willingness, training times, hospital support, medication preferences,and drug marketing.Conclusion The prescription rate of essential medicines in the sampled hospitals is low,and the targeted comprehensive intervention measures should be taken to promote prescription rate of essential medicines in county hospitals.

In this consideration,the paper described the imperatives of drug safety,constraints of governance by the government,and advantages of social co-governance,proposing the necessity to establish aFive-in-One (referring to the involvement of the government,enterprises,industry associations,media and the public) drug safety social co-governance.In its analysis of the present dilemma o[drug safety governance,the authors proposed such measures as perfecting legal and institutional system,reforming governmental power allocation mechanism,improving the incentive mechanism,innovating governance means and improving social governance ability,for the purpose of enhancing such a co-governance pattern.

CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) have been shown to play a regulatory or suppressive role in the immune response and are possibly relevant to the pathogenesis of autoimmune diseases. In the present study, we attempted to investigate the frequency of CD4+CD25+ Tregs in peripheral blood (PB) of collagen-induced arthritis (CIA) rats during the development of arthritis, to determine whether their frequency is involved in the immunoregulation of this disease. The results showed that normal rats had similar frequencies of CD4+CD25+ Tregs in PB during the experiment time, expressed as a percentage of CD4+CD25+Foxp3+ T cells among the CD4+ T lymphocyte population. In contrast, the frequency of CD4+CD25+Foxp3+ T cells in CIA rats was found to change during the development of arthritis. In CIA rats, there is a significant negative correlation between the frequency of CD4+CD25+Foxp3+ T cells and paw swelling (r=-0.786, p< 0.01). The relationship between the frequency of CD4+CD25+Foxp3+ T and immune activation was not found in normal rats. During the time course, the frequency of CD4+CD25+Foxp3+ T was lower in CIA rats than in normal ones. The data suggest that the frequency of PB CD4+CD25+ Tregs may be a promising marker for arthritis activity.
Animals ; Arthritis ; Arthritis, Experimental* ; Autoimmune Diseases ; Lymphocytes ; Rats* ; T-Lymphocytes ; T-Lymphocytes, Regulatory*

Objective To analyze the usage of antibiotics after renovation in the use of this present situation and existing problems of pediatrics.Methods By application of our self-developed analyzing system for the clinical use of antibacterial agents,the prescriptions of pediatric outpatient in 2012 was studied retrospectively and their rationality was evaluated.Results The antibiotic prescription rate was 37.7％ in pediatric outpatient and emergency in our hospital,their were 26 antibacterial agents in clinic use which were involved in 6 pharmacological group.The defined daily dose(DDD) analysis was adopted and the results have shown that macrolides (42.20％),cephalosporins (35.90％) and penicillins (20.90％) were the most prescribed antibiotics and most of them were oral medicines (72.2％) and non restrictive drug (61.0％).The antibacterial agents' s combination therapy rate was 2.4％.Irrational use of drugs mainly include the wrong way of administration (78.0％),application of antibiotics with no indications (21.3％) and irrational combined use of antibiotics (0.5％).Conclusion The application of antibiotics in our hospital pediatric basic structure reasonable,but there are still improper usage and dosage,no indication of medicine,etc.It is necessary to further improve and perfect the use and management of antimicrobial agents.

OBJECTIVE:To facilitate the evolvement of hospital pharmaceutical care.METHODS:The website of pharmacy department of Shanghai No.9People’s Hospital was programmed and exploited,and based on which the hospital pharmaceutical information service was carrying out.RESULTS:The website ran stably and fast;its maintenance was very convenient;pharmaceutical information was rich,the online communication between doctors and patents was available here and the application outcome proved to be satisfactory.CONCLUSION:Establishing hospital pharmaceutical website and carrying out online pharmaceutical care are of significance in the evolvement of hospital pharmacy work.

OBJECTIVE: To evaluate the in vitro MTT assay for determining the drug sensitivity in fresh human tu- mors. METHODS: We tested the samples from 75 patients with gastric cancer, 55 patients with colorectal carcinoma, 55 patients with bladder cancer and 6 patients with carcinoma of tongue. RESULTS: On the average, the MTT sensitive drug in the above - mentioned first three kinds of solid tumors corresponded with the drug used by clinican experience. The response rate in MTT sensitive group was 73. 8% (48/65) while only 34.0% (17/50) in the control group and 0% (0/10) in MTT resistant group. CONCLUSION: MTT assay appears to be useful in exploring the possible anticancer effect of arsenic trioxide on tongue cancer. This test demonstrats that the MTT assay is clinically useful on an individual basis to optimize chemotherapy.