Neurodegenerative diseases constitute a group of chronic disorders characterized by the progressive loss of neurons. Major neurodegenerative conditions include Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. Pathologically, these diseases are marked by the accumulation of aggregates formed by pathological proteins such as amyloid-β, tau, α-synuclein, and TAR DNA-binding protein 43. These proteins assemble into amyloid fibrils that undergo prion-like propagation and dissemination, ultimately inducing neurodegeneration. Understanding the biology of these protein aggregates is fundamental to elucidating the pathophysiology of neurodegenerative disorders. In this review, we summarize the molecular mechanisms underlying the aggregation and transmission of pathological proteins, the processes through which these protein aggregates trigger neurodegeneration, and the interactions between different pathological proteins. We also provide an overview of the current diagnostic approaches and therapeutic strategies targeting pathological protein aggregates.
Humans ; Neurodegenerative Diseases/metabolism* ; alpha-Synuclein/metabolism* ; Amyloid beta-Peptides/metabolism* ; tau Proteins/metabolism* ; Protein Aggregation, Pathological/metabolism* ; DNA-Binding Proteins/metabolism* ; Animals ; Protein Aggregates/physiology*

To investigate the effect of isthmin-1 (ISM1) on the invasion and metastasis of pancreatic cancer and its underlying mechanism, this study analyzed the expression of ISM1 in pancreatic cancer patients and normal pancreatic tissues using The Cancer Genome Atlas (TCGA) database. Western blot was employed to detect differences in ISM1 protein expression between pancreatic cancer cell lines (Aspc1, Bxpc3, PANC1, SW1990) and the pancreatic epithelial cell line (hPNE). Cell models with stable ISM1 overexpression and knockdown were constructed, and changes in cell migration and invasion capabilities were assessed via Transwell invasion assays and wound healing assays. Meanwhile, Western blot was used to detect the expression levels of key markers of epithelial-mesenchymal transition (EMT). Furthermore, TCGA and the Gene Expression Omnibus (GEO) database were utilized to analyze pathways regulated downstream of ISM1 and the mechanisms promoting pancreatic cancer invasion and metastasis. Immunoprecipitation combined with mass spectrometry (IP-MS) was used to screen for vimentin as an ISM1-binding protein, and the interaction between ISM1 and vimentin was verified by immunofluorescence and co-immunoprecipitation (Co-IP). Bxpc3 cells overexpressing ISM1 were treated with the protein synthesis inhibitor cycloheximide (CHX) to detect vimentin protein stability. The results indicate that ISM1 promotes the EMT process by inhibiting vimentin degradation, thereby enhancing the invasion and metastasis of pancreatic cancer. This study provides new experimental evidence for elucidating the mechanism of pancreatic cancer metastasis.

Dilated cardiomyopathy （DCM） is characterized by the main pathological changes of global cardiac enlargement， especially left ventricular enlargement. Clinical manifestations include decreased heart function， arrhythmia， thromboembolism， and even sudden death. It is one of the refractory cardiovascular diseases. Conservative drug treatment is still the main approach in clinical practice， but due to its unavoidable side effects such as low blood pressure， it is often difficult to achieve a satisfactory prognosis. The combination of traditional Chinese medicine and Western medicine can effectively improve side effects and enhance efficacy. The research has found that nuclear transcription factors-κB （NF-κB）， adenylate activated protein kinase （AMPK）/mammalian rapamycin target protein （mTOR）， transforming growth factor-β （TGF-β）/Smads， Toll like receptors （TLR） 4/c-Jun amino terminal kinase （JNK）， mitogen activated protein kinase （MAPK）， phosphatidylinositol 3-kinase （PI3K）/protein kinase （Akt）， and other signaling pathways play a crucial regulatory role in the occurrence and development of DCM. Traditional Chinese medicine can improve myocardial fibrosis， reverse ventricular remodeling， alleviate oxidative stress， and achieve anti-inflammatory and other effects by regulating the above signaling pathways， thus improving DCM. Due to its multi-target and multi-mechanism characteristics， it has the advantages of high safety and good tolerance and has become an important part of current clinical treatment.

Objective To explore the effect of Kangxian Yixin decoction on PKA/CaMKⅡ Signal Pathway and Mitochondrial membrane potential of cardiomyocyte hypertrophy in dilated cardiomyopathy rats.Methods Drinking furazolidone to duplicate the DCM rats model for 10 weeks,then the rats were checked by ultrasound,the successfully established model rats were randomly divided into model group,low dose Kangxian Yixin decoction group,middle dose Kangxian Yixin decoction group,high dose Kangxian Yixin decoction group and captopril group.Normal group was separated.After 4 weeks of drug intervention,This experiment was over,ATP,Ca2+-Mg2+-ATP enzymatic activity,CaMKⅡ,PKA and UCP2 mRNA were tested.H9c2 cardiomyocyte hypertrophy model was set up by norepinephrine,after 24 h of drug intervention,mitochondrial membrane potential was tested.Results Compared with the normal group,cardiomyocyte mitochondria were damaged in each model group,ATP,Ca2+-Mg2+-ATP enzymatic activity and PKA mRNA were lower,UCP2 mRNA and CaMKⅡ mRNA were higer,mitochondrial membrane potential obviously decreased(P<0.05 or P<0.01).The mitochondria were protected in every drug group,the tested indexes get well in different degree,especially in hige dose Kangxian Yixin decoction group(P<0.05 or P<0.01).Conclusion Kangxian Yixin decoction can reduce myocardial cell mitochondrial damage in model rats with DCM,improve myocardial cell energy metabolism and cardiac systolic and diastolic functions,one of the mechanisms may be optimizing PKA/CaMKⅡ signal pathway and improving mitochondrial membrane potential.

Objective To investigate the effect of ACOT4 expression on the formation of calcium oxalate stones.Methods The HK2 cell of human tubular epithelial cells was used as subject,HK2 cell was treated with calcium oxalate,and the expression of ACOT4 was interfered with by siRNA.The gene expression levels in HK2 cell were detected by qPCR and Western blot.The cell viability was de-tected by CCK-8 assay.The cell apoptosis was detected by flow cytometry.The cell damage was detected by LDH assay.The adhesion ability of HK2 cell to calcium oxalate crystals was detected by crystal adhesion experiment.Results Calcium oxalate could regulate the expression of ACOT4 in HK2 cell.Interfering with ACOT4 can significantly inhibit the proliferation ability of HK2 cell,and promote the effect of cell activity reduction,damage and apoptosis of calcium oxalate to HK2 cell.At the same time,interfering with ACOT4 can sig-nificantly promote the adhesion ability of HK2 cells to calcium oxalate crystals.Conclusion Knocking down of ACOT4 can promote the damage of calcium oxalate to HK2 cell and promote the adhesion ability of HK2 cell to calcium oxalate crystals.

Dilated cardiomyopathy(DCM)has a concealed onset with left or even whole heart enlargement as the main imaging manifestation.It is a common primary disease of heart failure and arrhythmia.With the continuous deepening of research in recent years,the intrinsic molecular mechanism of regulatory cell death(RCD)has gradually become clear.Researchers have found that the RCD mode plays a very important role in the occurrence and development of DCM.At present,the RCD modes involved in DCM mainly include apoptosis,necrotic apoptosis,pyroptosis,iron death,autophagy,and cuproptosis,and a certain correlation exists among them,which interact and regulate each other.This article provides an overview of the current research status on the mechanisms of the six RCD modes involved in DCM to provide a reference for future basic research and clinical applications.

Objective:To investigate the effect of internal fixation of medial support and lateral wall on initial weight-bearing stability of femoral intertrochanteric fracture after reconstruction of intertrochanteric fracture.Methods:Based on the digital model of Sawbones femur, intertrochanteric fracture models with different medial support and lateral wall states were constructed. Combined with various intramedullary and extramedullary fixation methods, the mechanical models after fixation were simplified, and seven mechanical simplified models were obtained. The individual body weight load (70 kg) was simulated by applying concentrated force (700 N) to the end nodes of the femoral head. Through the analysis and calculation of each model in StrucMaster software, the axial force, shear force, bending moment, displacement deformation, and support reaction force of each bar in each mechanical model were obtained, and the results were output through the supporting SMConsole.Results:The median bending moment of model 1 was 11.55(5.57, 18.00) N·m, and the median bending moment was 2.89(2.81, 2.94) rad. The median bending moment of model 2 was 13.72(9.30, 20.05) N·m, and the median bending moment was 2.93(2.77, 3.05) rad. The median bending moment of model 3 was 19.65(10.23, 26.11) N·m, and the median bending moment was 2.93 (2.77, 3.05) rad. The median bending moment of model 4 was 25.95(25.14, 36.70) N·m, and the median bending moment was 4.38(3.16, 5.15) rad. The median bending moment of model 5 was 13.66(7.99, 25.62) N·m, and the median bending moment was 3.50(3.32, 3.56) rad. The median bending moment of model 6 was 24.60(9.33, 29.37) N·m, and the median bending moment was 3.90(3.69, 4.10) rad. The median bending moment of model 7 was 41.14(0.16, 41.30) N·m, and the median bending moment was 5.50(5.50, 7.05) rad. The mechanical properties of model 1 were better than those of the other six models.Conclusion:The simplified mechanical model and its mechanical calculation analysis based on the lever reconstruction balance theory can be used to preliminarily reveal the mechanical characteristics of femoral intertrochanteric fractures after internal fixation. The internal fixation methods of the medial support and lateral wall of femoral intertrochanteric fracture reconstruction can improve the initial stability of the weight bearing after internal fixation of femoral intertrochanteric fractures and have guiding significance for the functional rehabilitation of early postoperative weight bearing.

Our hospital first used the housing and training information management platform in 2018 in order to improve the management efficiency and teaching quality of standardized resident training in the Department of Otolaryngology-Head and Neck Surgery. Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, through continuous optimization and upgrading of system functions and the mobile APP terminal, the integrated development of teaching and management and the maximization of resource sharing have been realized, thus making up for the defects and deficiencies of the traditional resident training management mode. Our practice shows that the new resident training management mode based on informatization mobile platform can not only save time and effort for departments to grasp all aspects of resident training management, but also enable residents to complete the resident training plan step by step and reasonably with improvement in their knowledge, skills, and competence. Therefore, the new resident training management mode has broad application prospects.

Humans ; Atrial Fibrillation/surgery* ; Left Atrial Appendage Closure ; Heart Atria/surgery* ; Catheter Ablation/methods* ; Atrial Appendage/surgery* ; Treatment Outcome

This article retrospectively analyzed the clinical data of 8 patients with vesicovaginal fistula after radiotherapy for cervical cancer admitted in our hospital from January 2015 to October 2021. All of them underwent cystostomy under local anesthesia. A single J tube of bilateral ureters was retained under cystoscope, and the single J tube was introduced into the fistula bag through the cystostomy opening. All patients wore diapers for a long time before operation, and used urine pads 0-2 pieces/day after operation. QOL score was 5.3±0.5 points before operation, and 2.5±0.5 points after operation. The patient's body odor basically disappeared. The vesicovaginal fistula can be repaired by surgery, but for patients who cannot be operated or failed repeatedly due to various reasons, a single J tube of bilateral ureters can be drawn out through the cystostomy opening, which can improve the quality of life of patients through minor trauma.