Alzheimer's disease （AD） is a common type of dementia， primarily characterized by cognitive and behavioral impairments as well as deficits in learning and memory. The progression of AD has imposed a significant economic burden on society and families. However， its exact pathogenesis has not yet been fully elucidated. Currently， available therapeutic drugs are limited and are often accompanied by serious adverse effects. Traditional Chinese medicines （TCMs） and their extracts are mostly natural products and possess advantages such as multi-pathway regulation and relatively few adverse reactions. Experimental studies have shown that TCMs exhibit great potential in the prevention and treatment of AD. For example， Huanglian Jieduang， Danggui Shaoyaosan， Kaixin San， Liuwei Dihuangwan， Buyang Huanwutang， as well as Ginseng Radix et Rhizoma， Astragali Radix， Uncariae Ramulus cum Uncis， Coptidis Rhizoma， Gardeniae Fructus， Ginkgo Folium， Salviae Miltiorrhizae Radix et Rhizoma， and Curcumae Longae Rhizoma， can reduce β-amyloid deposition， inhibit excessive Tau protein phosphorylation， restore mitochondrial function， alleviate oxidative stress， suppress neuroinflammation and apoptosis， repair synaptic function， and improve gut microbiota. This article mainly summarizes the effects of several TCMs and compound prescriptions on AD， aiming to provide a reference for subsequent TCM-based treatment of AD.

OBJECTIVE: Exploring the formation and aggregation of human islet amyloid polypeptide (hIAPP) (amylin) fibers is significant for promoting the prevention and treatment of type II diabetes mellitus (T2DM). Flavones in pomelo peel have visible biological activity in the anti-diabetes aspect. The present study aimed to investigate the effects of five flavones [naringin (NRG), narirutin (NRR), nobiletin (NOB), sinensetin (SIN), and neohesperidin (NHP)] in pomelo peel on peptide aggregation and explore its possible mechanisms. The cell viability of flavones against peptide aggregation was also evaluated. METHODS: The thioflavin T (ThT) assay and transmission electron microscopy (TEM) were used for evaluating the inhibition and disaggregation of flavones on peptide aggregation. The interaction mechanism was analyzed by endogenous fluorescence, molecular dynamics (MD) simulations, ultraviolet spectroscopy (UV) and isothermal titration calorimetry (ITC) experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and immune assays were performed to characterize the cell viability of flavones against peptide aggregation. RESULTS: The five flavones showed a decrease in fluorescence intensity, fiber number and size under incubation with different molar ratios of hIAPP. The compounds can bind to the aromatic tyrosine (Tyr) residueTyr 37, resulting in the intrinsic fluorescence quenching of the peptides. Five flavones can form hydrogen bonds with hIAPP, which is likely to be based on their phenolic hydroxyl structure. They showed strong binding affinity with peptides. The reaction system of NRG and NRR observed an exothermic reaction, and the others were endothermic reactions. The absorption peaks of the compounds with hIAPP changed and showed hypochromic effects, indicating that there may be π-π stacking interaction. Flavones noticeably increased the cell viability in the presence of amyloid peptides and reduced the absorption intensity induced by peptide oligomers. CONCLUSION A total of five flavones in pomelo peel have inhibitory and depolymerization effects on amyloid fibrils, and can significantly protect cells from the toxic effect of hIAPP and reduce the production of toxic oligomers.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

OBJECTIVE To analyze the value of elastic modulus of shear wave elastography in the diagnosis of cervical lymph node metastasis of thyroid cancer and its correlation with VEGF-C and VEGF-D.METHODS A total of 120 patients with thyroid cancer admitted to our hospital were divided into metastatic group(n=37)and non-metastatic group(n=83)according to whether the cervical lymph node metastasis.The clinical data and SWE elastic modulus values of the two groups were compared,and the effects of clinical characteristics on SWE elastic modulus values were analyzed by hierarchical regression.Logistic regression analysis was conducted to analyze the independent correlation between SWE elastic modulus and the risk of lymph node metastasis of thyroid cancer.The dose-response relationship between the elastic modulus of SWE and the risk of lymph node metastasis in thyroid cancer was analyzed with restricted cubic strips.The correlation between SWE elastic modulus and VEGF-C and D levels was analyzed after adjusting factors by Logistic regression.RESULTS The results of general data analysis showed that male proportion,BMI,clinical stage,lesion diameter,TSH,FT4,TgAb positive rate,TPOAb positive rate,VEGF-C and VEGF-D in metastatic group were higher than those in non-metastatic group.Under different clinical characteristics,SWE parameters Emax,Emean and Eratio in metastatic group were higher than those in non-metastatic group.In hierarchical regression analysis,gender,clinical stage,lesion diameter,biochemical indices(TSH,FT4,TgAb,TPOAb)had significant positive effects on SWE parameters.SWE parameters were independently associated with the risk of lymph node metastasis of thyroid cancer.Subgroup analysis showed that the association between SWE parameters and the risk of lymph node metastasis of thyroid cancer in all subgroups was statistically significant(P<0.05).There was no nonlinear dose-response relationship between SWE parameters and thyroid cancer risk(P>0.05).After adjusting for confounding factors,there was a significant linear correlation between Emax,Emean,Eratio and VEGF-C and VEGF-D(P<0.05).CONCLUSION The elastic modulus of SWE has a certain diagnostic value for lymph node metastasis of thyroid cancer,and SWE parameters have a certain correlation with VEGF-C and VEGF-D.

Objective:To compare the application effect of domestic and imported intravenous radiofrequency closure system in the treatment of primary varicose veins of lower extremities.Methods:This single-center prospective, non-inferiority randomized controlled trial was performed in the Department of Vascular Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine from January 2021 to January 2022. Patients with primary varicose veins of lower extremities who met the ataxation criteria were randomly assigned to the experimental group(domestic novel venous radiofrequency closure system) or the control group(imported venous radiofrequency closure system) in a ratio of 1∶1. The two groups of subjects were compared in terms of target vein closure rate, technical success rate, system operation performance, incidence of adverse events and incidence of serious adverse events(SAE) within 6 months after surgery. Quantitative data were compared by Mann-Whitney U test, and categorical data were compared by χ2 test and non-inferiority test. Results:A total of 80 subjects were included in the trial (41 in the experimental group and 39 in the control group), including 27 males and 53 females, aged ( M(IQR)) 55(23) years (range:40 to 78 years). There were 48 cases of left lower limb and 32 cases of right lower limb. The technical success rate and system control performance between the groups were 100%.The incidence of adverse events (58.5% (24/41) vs. 61.5% (24/39), χ2=0.075, P=0.784), and the incidence of SAE (7.3% (3/41) vs. 5.1% (2/39), χ2=0.163, P=0.686) within 6 months after surgery in experimental group and control group had no statistical significance. There was one device-related adverse event in each of the two groups. In the experimental group, one patient developed endovenous heat-induced thrombosis after surgery and recovered after taking rivaroxaban tablets. One patient in the control group had pain in the upper right thigh for more than 1 day after operation, which was cured after using analgesic cream. No device-related SAE occurred. The venous closure rate of the experimental group was 100% (38/38) at 6 months after surgery, and that of the control group was 97.4% (37/38). The difference between the two groups was 2.63% (95% CI:-3.19 to 8.45, Z=4.865, P<0.01), and the 95% CI lower limit of the difference in target venous closure rate between two groups was greater than the non-inferiority threshold of -10.00%. Conclusion:The early application effect of the new domestic intravenous radiofrequency closure system in patients with primary varicose veins of lower extremities is in line with expectations, it is not inferior to the imported system.

Objective:To compare the application effect of domestic and imported intravenous radiofrequency closure system in the treatment of primary varicose veins of lower extremities.Methods:This single-center prospective, non-inferiority randomized controlled trial was performed in the Department of Vascular Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine from January 2021 to January 2022. Patients with primary varicose veins of lower extremities who met the ataxation criteria were randomly assigned to the experimental group(domestic novel venous radiofrequency closure system) or the control group(imported venous radiofrequency closure system) in a ratio of 1∶1. The two groups of subjects were compared in terms of target vein closure rate, technical success rate, system operation performance, incidence of adverse events and incidence of serious adverse events(SAE) within 6 months after surgery. Quantitative data were compared by Mann-Whitney U test, and categorical data were compared by χ2 test and non-inferiority test. Results:A total of 80 subjects were included in the trial (41 in the experimental group and 39 in the control group), including 27 males and 53 females, aged ( M(IQR)) 55(23) years (range:40 to 78 years). There were 48 cases of left lower limb and 32 cases of right lower limb. The technical success rate and system control performance between the groups were 100%.The incidence of adverse events (58.5% (24/41) vs. 61.5% (24/39), χ2=0.075, P=0.784), and the incidence of SAE (7.3% (3/41) vs. 5.1% (2/39), χ2=0.163, P=0.686) within 6 months after surgery in experimental group and control group had no statistical significance. There was one device-related adverse event in each of the two groups. In the experimental group, one patient developed endovenous heat-induced thrombosis after surgery and recovered after taking rivaroxaban tablets. One patient in the control group had pain in the upper right thigh for more than 1 day after operation, which was cured after using analgesic cream. No device-related SAE occurred. The venous closure rate of the experimental group was 100% (38/38) at 6 months after surgery, and that of the control group was 97.4% (37/38). The difference between the two groups was 2.63% (95% CI:-3.19 to 8.45, Z=4.865, P<0.01), and the 95% CI lower limit of the difference in target venous closure rate between two groups was greater than the non-inferiority threshold of -10.00%. Conclusion:The early application effect of the new domestic intravenous radiofrequency closure system in patients with primary varicose veins of lower extremities is in line with expectations, it is not inferior to the imported system.

Objective To analyze the influencing factors of postoperative subsyndromal delirium in elderly patients undergoing abdominal surgery,and to develop a nomogram risk prediction model.Methods A convenience sampling method was used to select 497 elderly patients who underwent abdominal surgery in a tertiary hospital in Sichuan Province from February to October 2022.The risk prediction model and nomograms model were constructed using Logistic regression analysis and R software.The area under the subject's working characteristic curve(AUC)and Hosmer-Lemshow test were used to evaluate the discrimination and calibration of the model.Results The results of Logistic regression showed that age(OR=1.066),functional activities(OR=1.143),patient controlled intravenous analgesia(OR=5.811),transanal drainage tube(OR=2.276)and postoperative blood transfusion(OR=4.322)were independent influences on the occurrence of postoperative subsyndromal delirium.The p-values of the prediction model in both the training and validation sets were greater than 0.05;the area under the ROC curves were 0.734 and 0.691;the model was presented in the form of nomogram.Conclusion The prediction model developed in this study has good discrimination and accuracy.It can be used to assist clinical staff in identifying patients at high risk of developing postoperative subsyndromal delirium and provide the reference for developing preventive and intervention measures.

Objective:To explore the effect of comprehensive follow-up mode in patients with chronic obstructive pulmonary disease (COPD) .Methods:From February to June 2019, a total of 80 COPD patients in The First Affiliated Hospital of Guangxi Medical University were enrolled and divided into the control group and the comprehensive follow-up group (40 cases in each group) . All patients were given home rehabilitation program guidance and health education. The control group was followed up using telephone, while the comprehensive follow-up group were followed up by telephone combined with Internet which lasted for one year. The differences of pulmonary function, motor function, compliance and recurrence between the two groups were compared.Results:One year after discharge, percentage of forced vital capacity to the predicted value (FVC%) , percentage of forced expiratory volume in one second to the predicted value (FEV1%) , 6 minutes walking distance, SF-36 quality of life and rehabilitation compliance rate in the comprehensive follow-up group were higher than those of the control group, while CAT score, mMRC score, number of patients with acute attack of COPD and recurrence rate were lower than those of the the control group, and the differences were statistically significant ( P<0.05) . Conclusions:For CPOD patients, the comprehensive follow-up mode can effectively reduce the 1-year recurrence rate, promote the recovery of respiratory and motor functions, and improve compliance and quality of life.

Objective To analyze the dilemmas of our hierarchical medical system, in order to seek a viable path for effective implementation.Methods Based on the Meter-horn model, six related factors were used, including policy standards and goals, policy resources, implementation methods, characteristics of the actuator, value orientation of the executive and the system environment, to analyze the dilemmas of the implementation of hierarchical medical system.Results This policy had not achieved the expected effect in the implementation process, which deviated from the original intention of policy designers to some extent. There exist the following setbacks for the roadblocks. For example, policy standard was ambiguous, the policy resources were insufficient, the execution method was not proper, the implementation mechanism was"criticized" , the implementation personnel value orientation was biased and the complex system environment.Conclusions All the factors involved in the implementation of the hierarchical medical policy affect each other.In this consideration, medical institutions at all levels and the relevant departments should coordinate and deal with the relationship between these six related factors, and timely take effective measures to amend and improve the policy, so as to ensure the orderly progress and long-term implementation of the hierarchical medical system.

Objective: To investigate the efficacy and safety of rapamycin in children with tuberous sclerosis complex (TSC) associated renal disease. Methods: A prospective self-control study was conducted. The clinical data of 92 children diagnosed with tuberous sclerosis complex associated kidney disease at the People′s Liberation Army General Hospital from January 2011 to January 2019 were collected. The long-term rapamycin treatment for all patients initiated at 1 mg/(m²·d), which was gradually adjusted to reach a blood concentration of 5-10 μg/L. The changes of the maximum diameter of renal lesions in children after rapamycin treatment were observed and analyzed with Wilcoxon test. Results: Ninety-two children, including 52 males and 40 females, who met the criteria were analyzed. Sixty patients had only renal angiomyolipoma(RAML), while 24 patients had only multiple renal cysts(MRC), and 8 patients had both lesions. The age of TSC diagnosis was 16.0 (7.0, 42.0) months, and the age of initial treatment with rapamycin was 63.5 (21.0, 103.0) months. The follow-up lasted for 12.0 (4.0, 23.0) months. Sequencing of TSC1 and TSC2 genes was performed in 54 children with TSC, including 3 patients (6%) with mutations in TSC1 gene and 51 patients (94%) with mutations in TSC2 gene. The maximum RAML diameter before treatment was 7.0 (4.0, 9.0) mm. The best effect reached at 3 months of treatment, with the diameter of 4.0 (0,7.0) mm. The maximum diameters at 6 months, 1 year and 1-2 years were 5.0 (0,9.8) mm, 5.0 (1.5, 8.5) mm, 5.5 (3.0, 9.0) mm, respectively, and were significantly different from the baseline (Z=-2.404,-2.350,-2.750,P=0.016,0.019,0.006, respectively). The maximum diameter after 2-3 years, and ≥3 years were 5.0 (3.9,7.0) mm and 6.0 (1.0, 11.0) mm, without significant difference from the baseline (Z=-0.856,-0.102,P=0.393,0.919, respectively).The maximum diameters of MRC after 3 months, 6 months, 1 year,1-2 years, 2-3 years, and ≥3 years were 11.0 (5.0, 14.0) mm,3.0 (0.0,11.0) mm,5.0 (0,21.0) mm,0 (0,14.0) mm,0 (0,10.0) mm, and 0 (0,18.3) mm, respectively, but were not significantly different rom the baseline (7.0 (5.0, 15.7) mm)(Z=-0.944,-1.214,-1.035,-1.896,-1.603,-1.214,P=0.345,0.225,0.301,0.058,0.109,0.225, respectively).Twenty-nine patients (32%) had oral ulcers during the entire treatment period, and no serious adverse reactions were observed. Conclusions Rapamycin could decrease the diameter of TSC-related RAML, but could not inhibit the growth of cysts. It is well tolerated in the treatment of renal diseases associated with tuberous sclerosis complex.