Alzheimer's disease(AD)is the most common neurodegenerative disease in the elderly,and its main pathological manifestations include senile plaques formed by β-amyloid deposition and neuronal fibrillar nodules formed by hyperphosphorylation of tau proteins.Lysosome is an important organelle in eukaryotic cells,containing a variety of hydrolytic enzymes that can break down proteins and other biomolecules.It is closely related to intracellular transport and autophagy,and is important for maintaining cellular homeostasis.This review summarizes the interaction between lysosomal dysfunction and the development and progression of AD and the potential therapeutic mechanisms in treating AD by regulating and restoring the functions of lysosomes.Lysosomal dysfunction can lead to neurodegenerative diseases such as AD.Modulation of lysosomal function is a promising treatment strategy for AD.It is expected that more drugs and therapeutic regimens based on this mechanism can be used in the clinical treatment for AD patients in the future.

BACKGROUND:Obesity and its relevant chronic inflammation are important risk factors for inducing type 2 diabetes.This inflammatory response will further involve skeletal muscle,leading to an increase in catabolic and autophagic fluxes in skeletal muscle.Aerobic exercise is the mainstream mode of exercise in the prevention and treatment of type 2 diabetes,and may also has a certain protective effect on skeletal muscle. OBJECTIVE:To explore the effects and regulatory mechanisms of aerobic exercise on glucolipid metabolism,skeletal muscle inflammation and autophagy in type 2 diabetic rats. METHODS:Animal models of type 2 diabetes were established in rats by 8-week high-fat feeding combined with streptozotocin injection,and the experimental rats were then divided into normal control group,normal exercise group,diabetic control group and diabetic exercise group.The exercise group performed 4 weeks of aerobic exercise(16 m/min,60 min/d,5 d/wk).The levels of blood glucose,high-density lipoprotein,low-density lipoprotein and triglyceride in serum were measured by an automated biochemical analyzer.Serum insulin level was determined using enzyme-linked immunosorbent assay and the insulin resistance index and area under the glucose metabolism curve were calculated.The levels of interleukin 6 and tumor necrosis factor α in skeletal muscle were measured by enzyme-linked immunosorbent assay after 4 weeks of aerobic exercise,and the expression levels of forkhead box protein O3(FoxO3),LC3 and p62 in skeletal muscle were measured by western blot assay. RESULTS AND CONCLUSION:The area under the glucose tolerance curve and insulin resistance index both increased significantly in type 2 diabetic rats(P<0.001,P=0.025),and aerobic exercise significantly reduced the area under the glucose tolerance curve and insulin resistance index in the normal exercise group(P<0.001,P=0.038)and diabetic exercise group(P<0.001,P=0.004).Serum high-density lipoprotein significantly decreased(P=0.030),and low-density lipoprotein and triglyceride(P=0.027,P=0.014)levels significantly increased in the diabetic control group compared with the normal control group.Aerobic exercise significantly reduced triglyceride and low-density lipoprotein levels in the normal exercise group(P=0.019,P=0.008)as well as triglyceride levels in the diabetic exercise group(P=0.022).Both interleukin-6 and tumor necrosis factor α levels were significantly increased in the skeletal muscle of type 2 diabetic rats compared with the normal control group(P<0.001,P=0.007),and aerobic exercise significantly reduced tumor necrosis factor α levels in the diabetic exercise group(P=0.017).The LC3-Ⅱ/LC3-I was significantly increased in the skeletal muscle of type 2 diabetic rats compared with the normal control group.Aerobic exercise significantly increased the LC3-Ⅱ/LC3-I in the normal exercise group(P<0.001)and decreased the LC3-Ⅱ/LC3-I,FoxO3 and p62 protein expression levels in the diabetic exercise group(P=0.026,P=0.050,P=0.048).To conclusion,type 2 diabetes model established by high-fat feeding combined with streptozotocin injection has obvious glycolipid metabolism disorder,and leads to inflammatory response and excessive activation of autophagy in skeletal muscle.Aerobic exercise can improve glycolipid metabolism,reduce local inflammation in skeletal muscle and inhibit autophagy,and finally play a protective role in skeletal muscle.

BACKGROUND:The threaded conical implant has a good ability to control micro movements and is conducive to immediate loading.However,the effects of double-threaded conical cylindrical implants and conical cylindrical implants on stress distribution and initial stability of implant-bone interface after immediate loading have not been reported. OBJECTIVE:To investigate the impact of double-threaded conical cylindrical implants and conical cylindrical implants on the biological distribution of the implant and the surrounding bone interface during immediate loading in the mandibular molar region. METHODS:(1)Three-dimensional finite element analysis:Conical beam CT scans of the mandible and first molar of a volunteer were used to develop a basal model of the mandible.The double-threaded conical cylindrical implants and conical cylindrical implants were assembled with the mandibular models,and an immediate-load(or delayed implantation)implant model(a total of four models)for the first mandibular molar was established.Loads in four directions(100 N):axial,lingual and buccal 45°,mesial and distal,and buccal and lingual,were applied to the central fossa of each model's crown.Three-dimensional finite element method was used to analyze the implant displacement and the stress distribution at the implant-bone interface.(2)In vitro experiment:With the assistance of the oral implant robot,the double-threaded conical cylindrical implants and conical cylindrical implants were implanted on the same artificial bone pieces,separately,and the immediate load model of immediate implant implantation(or delayed implantation)was established in vitro(a total of four groups of models).Osstell resonance frequency analyzer and SmartPeg sensor were used to measure the implant stability coefficient in four vertical directions:front,rear,left,and right measurements,evaluate the initial stability,and verify the finite element analysis results. RESULTS AND CONCLUSION:(1)The displacement difference between double-threaded conical cylindrical implants and conical cylindrical implants was small when the immediate loading of delayed implantation was applied,but the maximum stress value of conical cylindrical implant-bone interface was greater than that of double-threaded conical cylindrical implant-bone interface.When the immediate loading of immediate implantation was applied,the maximum stress value and the maximum displacement of bone around the implant appeared when the load was applied in mesiodistal direction.The stress value of the conical cylindrical implant reached 298.84 MPa and the maximum displacement was 0.31 mm,both of which were larger than that of the double-threaded conical cylindrical implant.(2)The results of in vitro experiments showed that the stability coefficient of the double-threaded conical cylindrical implant was greater than that of the conical cylindrical implant.(3)Compared with the conical cylindrical implant,the double-threaded conical cylindrical implant has higher initial stability under immediate loading,suggesting that the use of double-threaded conical cylindrical implant should be given priority in clinical immediate loading.

This article reports a case of acute kidney injury (AKI) following near drowning with reduced urine output as the main manifestation. The patient was a 37-year-old middle-aged man. His renal function deteriorated sharply after accidentally falling into the water, and renal pathology showed acute tubular injury. After hemodialysis treatment, urine output increased significantly, and renal function and proteinuria improved significantly. AKI following near drowning lacks typical clinical manifestations and is prone to delayed diagnosis and treatment. The patients with a history of near drowning should be followed up to determine whether they are complicated by AKI.

Objective To investigate the correlation of circular RNA-ZNF532(cZNF532)expression level with pancreatic islet cell function and microvascular complications in patients with type 2 diabetes mellitus(T2DM).Methods A total of 198 T2DM patients admitted to the Department of Endocrinology,Nanyang Central Hospital from June 2018 to June 2022 were selected as the research subjects(observation group),and 50 healthy volunteers who underwent physical examination in the hospital during the same period were selected as the control group.The expression level of cZNF532 in peripheral blood mononuclear cells was detected by real-time fluorescence quantitative polymerase chain reaction,the fasting blood glucose(FPG),insulin(FINS),glycosylated hemoglobin(HbA1c),homeostatic model assessment of insulin resistance(HOMA-IR)and homeostasis model assessment of β-cell function(HOMA-β)of the subjects were detected by the fully automated biochemical analyzer,and the correlation between cZNF532 expression level and pancreatic islet cell function in T2DM patients was analyzed by Pearson correlation analysis.The clinical data of T2DM patients were collected,and they were divided into microvascular complication group(n=120)and non-microvascular complication group(n=78)according to whether microvascular complications occurred during treatment.Multivariate logistic regression analysis was used to identify the risk factors for microvascular complications in patients with T2DM,and Spearman correlation analysis was used to explore the correlation between the expression level of cZNF532 and microvascular complications in patients with T2DM.Results Compared with the control group,the levels of cZNF532,FINS,HbA1c and HOMA-IR were significantly higher and HOMA-β was significantly lower in the observation group(P＜0.05).The results of Pearson correlation analysis showed that the expression level of cZNF532 in T2DM patients was positively correlated with the FINS,HbA1c and HOMA-IR(r=0.324,0.357,0.410;P＜0.05);and negatively correlated with HOMA-β(r=-0.389,P＜0.05).There was no significant difference in gender,age,course of disease,number of patients with hypertension,high-density lipoprotein cholesterol(HDL-C),total cholesterol(TC)and triglyceride(TG)levels between the microvascular complication group and the non-microvascular complication group(P＞0.05);compared with the non-microvascular complication group,the expression levels of LDL-C,FPG and cZNF532 in the microvascular complication group were significantly higher(P＜0.05).Multivariate logistic regression analysis showed that LDL-C,FPG and cZNF532 were independent risk factors for microvascular complications in T2DM patients.The results of Spearman correlation analysis showed that the expression level of cZNF532 was positively correlated with the occurrence of microvascular complications in T2DM patients(r=0.681,P＜0.05).Conclusion cZNF532 is overexpressed in T2DM patients,which is associated with pancreatic islet cell function and microvascular complications in T2DM patients.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objective:To construct a value evaluation framework for high-value medical consumables,providing a guidance for medical insurance access and hospital access management scenarios in China.Methods:It conducted literature review,qualitative in-terviews and quantitative surveys.A total of 12 experts were invited for qualitative interviews,while 100 experts from four fields of health technology assessment,medical insurance,hospital management,and clinical practice participated in the quantitative survey.Through those process,it generated the composition of the value framework and the scoring of each item.Differences in ratings be-tween different scenarios and experts were analyzed through chi-square tests.The recommendation level for each item was graded.Re-sults:A comprehensive value evaluation framework for high-value medical consumables was established,which included 6 core dimen-sions,comprised 16 items for secondary dimensions and 50 items for tertiary dimensions.It showed significant differences between the medical insurance access and hospital access scenarios,as well as among different fields of experts in the same scenario.furthermore,grading the items in two scenarios.The medical insurance access scenario had 8 highly recommended items,and the hospital access scenario had 24 highly recommended items.Conclusion:Value evaluation should encourage multi-dimensional assessments and inter-disciplinary participation,continually improving the management of high-value medical consumables in medical insurance and hospital access.

A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.
Female ; Male ; Humans ; Cisplatin/pharmacology* ; Disulfiram/pharmacology* ; Testicular Neoplasms/drug therapy* ; Fanconi Anemia/drug therapy* ; Alcoholism/drug therapy* ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Substance Withdrawal Syndrome/drug therapy* ; Apoptosis ; Antineoplastic Agents/therapeutic use* ; Cell Proliferation

As the most efficient perception system in nature, the perception mechanism of the insect (such as honeybee) antennae is the key to imitating the high-performance sensor technology. An automated experimental device suitable for collecting electrical signals (including antenna reaction time information) of antennae was developed, in response to the problems of the non-standardized experimental process, interference of manual operation, and low efficiency in the study of antenna perception mechanism. Firstly, aiming at the automatic identification and location of insect heads in experiments, the image templates of insect head contour features were established. Insect heads were template-matched based on the Hausdorff method. Then, for the angle deviation of the insect heads relative to the standard detection position, a method that calculates the angle of the insect head mid-axis based on the minimum external rectangle of the long axis was proposed. Eventually, the electrical signals generated by the antennae in contact with the reagents were collected by the electrical signal acquisition device. Honeybees were used as the research object in this study. The experimental results showed that the accuracy of template matching could reach 95.3% to locate the bee head quickly, and the deviation angle of the bee head was less than 1°. The distance between antennae and experimental reagents could meet the requirements of antennae perception experiments. The parameters, such as the contact reaction time of honeybee antennae to sucrose solution, were consistent with the results of the manual experiment. The system collects effectively antenna contact signals in an undisturbed state and realizes the standardization of experiments on antenna perception mechanisms, which provides an experimental method and device for studying and analyzing the reaction time of the antenna involved in biological antenna perception mechanisms.
Animals ; Arthropod Antennae ; Bees