Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by memory loss and cognitive dysfunction. The accumulation of misfolded protein aggregates including amyloid beta (Aβ) peptides and microtubule associated protein tau (MAPT/tau) in neuronal cells are hallmarks of AD. So far, the exact underlying mechanisms for the aetiologies of AD have not been fully understood and the effective treatment for AD is limited. Autophagy is an evolutionarily conserved cellular catabolic process by which damaged cellular organelles and protein aggregates are degraded via lysosomes. Recently, there is accumulating evidence linking the impairment of the autophagy-lysosomal pathway with AD pathogenesis. Interestingly, the enhancement of autophagy to remove protein aggregates has been proposed as a promising therapeutic strategy for AD. Here, we first summarize the recent genetic, pathological and experimental studies regarding the impairment of the autophagy-lysosomal pathway in AD. We then describe the interplay between the autophagy-lysosomal pathway and two pathological proteins, Aβ and MAPT/tau, in AD. Finally, we discuss potential therapeutic strategies and small molecules that target the autophagy-lysosomal pathway for AD treatment both in animal models and in clinical trials. Overall, this article highlights the pivotal functions of the autophagy-lysosomal pathway in AD pathogenesis and potential druggable targets in the autophagy-lysosomal pathway for AD treatment.

The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.
Adult ; Asian Continental Ancestry Group ; Biomarkers ; China ; Consensus ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Eosinophils ; Epidemiology ; Epigenomics ; Genetics ; Humans ; Hypersensitivity ; Inflammation ; International Agencies ; Medical Staff ; Neck ; Phenotype ; Precision Medicine

Objective To evaluate the safety of morphine hydrochloride injection. Methods Ear verin injection was used to evaluate the vascular irritation using the comparison of left side with right side in rabbits. Quadriceps femoris injection was used to evaluate the muscle irritation using the comparison of left side with right side in rabbits. Guinea pigs were intravenously injected with morphine hydrochloride injection at a dose of 2.8 mg·kg-1 once daily 3 times, stimulation was performed on 14 d after the last sensitization and the booster dose was 2 times the sensitization dose. The allergic reactions were observed. The different concentrations of morphine hydrochloride injection were placed in 2％ rabbit erythrocyte suspension, and then the hemolyzation and agglutination were observed. Results There were no significant vascular or muscular irritation and injury effects of morphine hydrochloride injection in rabbits. There were no evidenceof hemolyzation and agglutination in rabbit erythrocytes in vitro. No allergic reactions on guinea pigs in vivo were observed. Conclusion After treatment of morphine hydrochloride injection, neither obvious vascular /muscle stimulation or sensitization, nor hemolyzation or agglutination appeared in rabbits. The research results provide basic reference for the clinical rational and safe application of morphine hydrochloride injection.

Objective To investigate the middle-term clinical and radiological outcomes of self-locking and zero-profile cages for the treatment of multi-segmental cervical spondylosis in elderly patients through anterior decompression and fusion approach.Methods A total of 39 old patients with multi-segmental cervical spondylosis who received anterior cervical decompression and internal fixation with self-locking and zero-profile cages from January 2013 to January 2015 were retrospectively analyzed.The operation time,intraoperative bleeding volume and post-operational complications were recorded.The functions of cervical spine before and 1-month,1-year,the last follow-up after treatment were evaluated by using the neck pain visual analogue scale(VAS) score,the Japanese orthopedic association (JOA)score and neck disability index (NDI)score.The subjective satisfaction at the final follow-up was evaluated by using Odom's criteria.The whole cervical spine curvature,the range of motion of cervical spine,the height of fused segment,Cobb angle of fused segment,C2～C7 line of force at sagittal view,Cage sedimentation rate and fusion rate before and 1-month and 1-year and the last follow-up after treatment were evaluated by using X-ray and CT and compared between the two groups.Results All patients were followed up,and the mean follow-up time was(35.0±5.3)months(24-48 months).The average operation time was(110.0±21.3)min(85-180 min).The average intraoperative bleeding volum was (50.3 ± 10.6)ml (20-150 ml).There were significant differences in JOA and NDI scores before versus at 1-month,1-year and the final follow-up after treatment(F=9.93 and 28.21,P=0.001 and 0.001).The VAS score of neck pain was lower at 1-month,1-year follow-up than at pre-treatment(P＜0.05),while there were no significant differences in VAS score before treatment versus at the final treatment(P＞0.05).The fineness rate by the Odom criteria was 84.6 ％ (33/39 cases)at the final follow-up.The whole cervical spine curvature,the height of fused segment,the Cobb angle of fused segment and C2-C7 line of force at sagittal view were significantly improved at 1-month,1-year and the final follow-up versus pre-treatment(P＜0.05).The improvements in whole cervical spine curvature and the height of fused segment were lost in some degree with the time extension of follow-up,and the degree of improvements losing was higher at the final follow-up than at 1-year follow-up.At last follow up and in all of patients,the rate of segment fusion were 87.2 ％ (102/117 cases) and Cage sedimentation rate was still 21.4 ％ (25/117 cases).Conclusions Self-locking and zero-profile cages can shorten the operation time,reduce the incidence of postoperative dysphagia,and have good clinical efficacy and fusion rate.But the improvements in cervical spine curvature and the height of fused segement are gradually lost,and the cage has a subsidence in some degree in the middle-term follow-up.Thus,a comprehensive consideration is still needed when choosing self-locking and zero-profile cages for clinical application.

Objective: To analyze the effect of diary psychological guidance on negative emotion and self-efficacy in patients with duodenal ulcer. Methods: From August 2016 to September 2018, 88 patients with duodenal bulbar ulcer admitted to Harrison International Peace Hospital were divided into study group and control group by random grouping method, 44 cases in each group. The control group was given traditional intervention, while the study group was given diary psychological guidance on the basis of the control group. Both groups were assessed by SAS and SDS, Pittsburgh Sleep Scale, SF-36 Quality of Life Scale and Self-efficacy Scale before and after intervention at the end of the second week. Results: After intervention, SAS and SDS of the study group were (51.3±2.0), (52.4±1.9) respectively, while those of the control group were (58.5±2.8), (59.3±3.1). There were significant differences between the two groups (t=15.278, 13.211, P < 0.05). The Pittsburgh sleep quality score, self-efficacy score and quality of life score in the study group were higher than those in the control group (t=7.892-24.031, all P<0.05). Conclusion The intervention of diary psychological guidance can improve the negative emotions such as anxiety and depression, and improve the self-efficacy of patients with duodenal ulcer.

Objective To investigate the establishment,operation and performance of external quality assessment(EQA) system for microbial morphology and detection of special drug-resistance in clinical laboratory,and explore the value of the developed system in clinical application.Methods The pictures of known bacteria and fungi colony,gram staining and acid-fast staining from clinical microbiology were distributed to the participating laboratories in Gansu province twice a year at regular intervals.The pictures of standard knowledge points from CLSI,such as special drug resistance were distributed simultaneously.All the participating laboratories were required to complete the interpretation for the pictures and report their resuhs in a scheduled time.Then the resuhs were summarized and analyzed as 3 modes:complete consistency,general consistency and non-consistency.Results During the 2 years when the EQA system for microbial morphology and detection of special drug-resistance were performed for 24 times,the rate of annual complete consistency increased year by year and reached to 91.3％ in 2015.Conclusion The EQA system based on the examinations of microbial morphology and CLSI standard knowledge points for clinical laboratory may supervise the staff of clinical microbiology laboratories in the hospitals at second grade or above to master the skills of morphological identification and learn CLSI knowledge points,so their professional skills of clinical microbiology could be comprehensively improved.

Objective · To investigate association between serum 25-hydroxyvitamin D3 [25(OH)D3] level and diabetic peripheral neuropathy (DPN) in elderly patients with type 2 diabetes mellitus and explore its value in clinical practice for early screening and prevention of DPN. Methods · A total of 188 elderly patients with type 2 diabetes mellitus were enrolled in this cross-sectional study, including 100cases with DPN and 88 cases without. Clinical data was collected and serum levels of 25(OH)D3, glycosylated hemoglobin (HbA1c), blood lipids and hepatic and renal functions were determined in all patients. Spearman correlation analysis was used to evaluate relationship between each index and 25(OH)D3, and Logistic regression was used for statistical analysis of risk factors for DPN. Results · The median of serum 25(OH)D3 level was significantly lower in the patients with DPN (34.95 nmol/L) than that of the patients without DPN (52.6 nmol/L)(P<0.01). Spearmancorrelation analysis showed that there existed a negative correlation between the level of 25(OH)D3 and age, HbA1c and fasting blood glucose (r=-0.37, -0.53, and -0.29, respectively, P<0.01). The multiple Logistical regression analysis revealed that the 25(OH)D3 level was an independent risk factor for DPN. The odds ratio of serum 25(OH)D3 was 15.5 (OR=15.50, 95% CI=2.00 ~ 119.62) for the lowest quartile versus the highest quartile. Conclusion · The decreased level of 25(OH)D3 may increase risks for the occurrence of DPN in the elders with type 2 diabetes mellitus and monitoring the level of 25(OH)D3 contributes to early detection of DPN.

OBJECTIVETo investigate the effects of interim hemodialysis (HD) on survival and clinical outcomes in patients with maintenance peritoneal dialysis (PD).

METHODSThe clinical data of 908 patients undergoing maintenance PD from January 2010 to December 2014 registered in Zhejiang Dialysis Regisration System were retrospectively analyzed. Among all PD patients, 176 cases received interim HD for less than 3 months, and then transferred to PD (transfer group) and 732 cases had initial PD (non-transfer group). The demographic parameters, biochemical data, comorbidity, details of peritonitis and transplantation were documented. Survival curves were made by the Kaplan-Meier method; univariate and multivariate analyses were performed with Cox proportional hazard regression model to identify risk factors of mortality.

RESULTSCompared with patients in transfer group, patients in non-transfer group had significantly higher serum albumin and total Kt/V levels. The survival rate was significantly higher in non-transfer group, but there was no significant difference in technique survival between two groups. After multivariable adjustment, initial dialysis modality (HR=1.60, 95% CI: 1.01~2.56), age (HR=1.07, 95% CI:1.05~1.09) and serum albumin (HR=0.96, 95% CI: 0.93~0.99) and Charslon comorbidity index (HR=2.54, 95% CI:1.63~3.94) were independent factors for long-term survival.

CONCLUSIONPatients who transfer to PD after interim HD have lower survival rate than patients who start with and are maintained on PD. HD is an independent risk factor for PD patients, therefore, patients with PD should be well informed and educated with dialysis protocols.

Humans ; Kidney Failure, Chronic ; mortality ; therapy ; Peritoneal Dialysis ; Proportional Hazards Models ; Renal Dialysis ; Retrospective Studies ; Risk Factors ; Survival Rate

BACKGROUND:Recently, there are many documents al over the world reporting hypotoxicity infection after fracture internal fixation surgery, but reports are different on whether it is necessary for chronic hypotoxicity infection internal fixation removal post surgery. There are no fixed judgment criteria of curative effects, which leads to inexact conclusion of treatment method. ＜br> OBJECTIVE:To observe the curative effects of taking rifampicin and ciprofloxacin with transfer of skin flap in the treatment of chronic hypotoxicity infection with sinus formation after fracture surgery on tibial plateau and ankle. METHODS:A total of 56 cases of chronic hypotoxicity infection after fracture surgery of tibial plateau and ankle were col ected from September 2005 to December 2012. 30 cases in the therapy group were treated with ＜br> levofloxacin and rifampicin with transfer of skin flap. 26 cases in the control group were treated with conventional intravenous antibiotics with local debridement to remove internal fixation. In both groups, the course of disease was 3 to 6 months. The erythrocyte sedimentation rate, kidney function and radiographic indices were reviewed every 1 to 3 months, and curative effects were evaluated. ＜br> RESULTS AND CONCLUSION:During the fol ow-up visit of 6-24 months, no recurrence happened to the cured and improved patients. In the therapy group, 24 cases were cured, 4 cases were improved, and 2 cases were invalid, with a total effective rate of 93%. In the control group, 11 cases were cured, 6 cases were improved and 9 cases were invalid with the total effective rate of 65%.χ2 test showed that therapeutic effects were significantly better in the therapy group than in the control group (P＜0.05). These data indicated that rifampicin and ciprofloxacin with transfer of skin flap for chronic hypotoxicity infection with sinus formation after fracture surgery of tibial plateau and ankle showed good curative effects.