Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects upper and lower motor neurons, and its mechanism has not been fully elucidated. In recent years, studies have shown that TAR DNA binding protein-43 (TDP-43) can affect neuronal function through multiple pathways and is closely related to the clinical manifestations and prognoses of ALS patients, suggesting that TDP-43 pathology may be an important target for the diagnosis and treatment of ALS. This article reviews the research progress on role of TDP-43 pathology in pathological mechanism of ALS and its application in diagnosis and treatment of ALS, aiming to provide reference for diagnosis and treatment of ALS.

Purpose To assess the utility of echocardiographic parameters in predicting adverse cardiovascular in patients with connective tissue disease.Materials and Methods A retrospective analysis was conducted on the clinical and echocardiographic records of patients with connective tissue disease from the Affiliated Hospital of Inner Mongolia Medical University(June 1st,2020 to June 1st,2023)who had complete medical data and at least twelve months of follow-up.Variables were screened based on univariate analysis,combined with clinical expertise and XGBoost feature weight analysis;this information was used to construct a Cox proportional hazards regression model designed to predict composite endpoint events of adverse cardiovascular outcomes.Internal validation was performed using the Bootstrap resampling method,and the model's performance was evaluated.Results The study included 123 participants.The incidence of positive events reached 39.02%(48/123).Mitral valve early diastolic annular velocity(reflecting left heart function)(HR=0.79,P=0.041)and tricuspid annular plane systolic excursion(reflecting right heart function)(HR=0.92,P=0.044)emerged as significant predictors for adverse cardiovascular outcomes.Compared with the clinical model,the model combined with left heart function parameters showed significant improvements in both risk classification and absolute accuracy for short-term and medium-term adverse prognosis(NRI365=0.054,IDI365=0.060,NRI730=0.064,IDI730=0.079,all P<0.05)and optimized risk classification for long-term adverse prognosis(NRI1 095=0.256,P<0.05).In contrast,the model combined with right heart function parameters improved risk classification at all time points(NRI365=0.054,NRI730=0.000,NRI1 095=0.135,all P<0.05).Conclusion Mitral valve early diastolic annular velocity and tricuspid annular plane systolic excursion,which reflect cardiac function,are factors for predicting adverse cardiovascular outcomes among individuals diagnosed with connective tissue disease.Multi-parameter combined models incorporating echocardiographic variables can provide incremental predictive value compared with clinical models.

Purpose To investigate the predictive value of nomogram based on preoperative CT imaging for predicting programmed cell death receptor ligand 1(PD-L1)expression in patient with lung adenocarcinoma.Materials and Methods A total of 158 patients with lung adenocarcinoma were enrolled in Shenzhen people's Hospital from January 2021 to July 2022,of which 82 were negative for PD-L1 and 76 were positive for PD-L1.They were randomly divided into training set(n=119)and verification set(n=39)according to the proportion of 7:3.The significant characteristics between PD-L1 negative and PD-L1 positive were screened by univariate and multivariate Logistic regression to construct a clinical model.Radiomics features were extracted from preoperative CT images,and then features were screened and modeled.Finally,the combined model was established by clinical factors and radiomics features,which was visualized by nomogram.The diagnostic performance of the model was evaluated using receiver operating characteristic curves and area under the curve(AUC).Results The area under the curve(AUC)of the clinical model composed of carcinoembryonic antigen and vascular convergence sign was 0.774(95%CI 0.687-0.860)and 0.808(95%CI 0.670-0.947)in the training set and validation set,respectively.Through feature screening,the radiomics model was composed of 17 radiomics features,and the AUC of the training and validation sets was 0.837(95%CI 0.764-0.910)and 0.778(95%CI 0.633-0.923).The training set and validation set of the combined model composed of carcinoembryonic antigen,vascular convergence sign and radiomics score were AUC 0.892(95%CI 0.832-0.952)and 0.853(95%CI 0.737-0.968).In the training set,the AUC of the combined model was higher than that of the other two models(Z=-2.640,-2.855,P＜0.05).Conclusion Based on preoperative CT radiomics nomogram,it had high predictive efficacy on the expression of PD-L1 in lung adenocarcinoma and could provide decision-making support for the selection of clinical treatment regimens for lung adenocarcinoma patients.

Objective To compare the hematological parameters,biochemical profiles,histopathological characteristics,and cytokines associated with lipid metabolism in 8-weeks-old specific pathogen-free(SPF)grade and germ-free(GF)golden hamsters.Methods Twenty 8-weeks-old SPF grade and GF golden hamsters,with equal numbers of males and females,were utilized in this study.Serum cytokines associated with routine blood parameters,blood biochemistry,and lipid metabolism were quantified using automated hematology and biochemical analyzers,and enzyme-linked immunosorbent assay kits.The cecum,small intestine,lung,spleen,forestomach,and glandular stomach were examined by histopathology.Results We compared the result between SPF grade and GF golden hamsters at 8 weeks of age.Regarding hematological parameters,females showed significant differences(P＜0.05)in white blood cell count,hemoglobin concentration,mean corpuscular hemoglobin(MCH),and mean platelet volume between the two groups,and highly significant differences(P＜0.001)in MCH concentration(MCHC),platelet distribution width(PDW),and lymphocyte count(LYM).Males showed significant differences(P＜0.05)in mean corpuscular volume,MCH,LYM,neutrophil count,basophil count,and basophil percentage,and highly significant differences(P＜0.001)in MCHC,PDW,lymphocyte percentage,and neutrophil percentage.In terms of biochemical parameters,females showed significant differences(P＜0.05)in low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol,fasting insulin(FINS),and glycosylated serum protein(GSP),and highly significant differences(P＜0.001)in triglycerides(TG).Males showed significant differences(P＜0.05)in GSP levels and highly significant differences(P＜0.001)in total cholesterol,TG,LDL-C,FINS,and C-peptide levels.For serum cytokines related to lipid metabolism,females showed significant differences(P＜0.05)in interleukin(IL)-10,adiponectin(ADP),and IL-6 levels,and highly significant differences(P＜0.001)in high-sensitivity C-reactive protein(hs-CRP).Males showed significant differences(P＜0.05)in hs-CRP levels and highly significant differences(P＜0.001)in ADP and tumor necrosis factor-alpha levels.Hematoxylin/eosin staining showed that the cecal muscle layer was thinner and the number of crypts attached to the mucous membrane was reduced in GF compared with SPF grade golden hamsters.In addition,the ileocele was enlarged and the number of goblet cells was increased,the alveolar septum was widened,immune cells in the white pulp of the spleen were increased,and the blood content in the blood sinuses was increased.There was also thinning of the anterior gastric mucosa and the basophilic strength of the glandular gastric tube gland was weakened.Conclusions This study established the differences in routine blood parameters,blood biochemistry indicators,histopathological features,and cytokines associated with lipid metabolism between 8-weeks-old SPF grade and GF golden hamsters,to establish preliminary reference ranges.

Purpose To assess the utility of echocardiographic parameters in predicting adverse cardiovascular in patients with connective tissue disease.Materials and Methods A retrospective analysis was conducted on the clinical and echocardiographic records of patients with connective tissue disease from the Affiliated Hospital of Inner Mongolia Medical University(June 1st,2020 to June 1st,2023)who had complete medical data and at least twelve months of follow-up.Variables were screened based on univariate analysis,combined with clinical expertise and XGBoost feature weight analysis;this information was used to construct a Cox proportional hazards regression model designed to predict composite endpoint events of adverse cardiovascular outcomes.Internal validation was performed using the Bootstrap resampling method,and the model's performance was evaluated.Results The study included 123 participants.The incidence of positive events reached 39.02%(48/123).Mitral valve early diastolic annular velocity(reflecting left heart function)(HR=0.79,P=0.041)and tricuspid annular plane systolic excursion(reflecting right heart function)(HR=0.92,P=0.044)emerged as significant predictors for adverse cardiovascular outcomes.Compared with the clinical model,the model combined with left heart function parameters showed significant improvements in both risk classification and absolute accuracy for short-term and medium-term adverse prognosis(NRI365=0.054,IDI365=0.060,NRI730=0.064,IDI730=0.079,all P<0.05)and optimized risk classification for long-term adverse prognosis(NRI1 095=0.256,P<0.05).In contrast,the model combined with right heart function parameters improved risk classification at all time points(NRI365=0.054,NRI730=0.000,NRI1 095=0.135,all P<0.05).Conclusion Mitral valve early diastolic annular velocity and tricuspid annular plane systolic excursion,which reflect cardiac function,are factors for predicting adverse cardiovascular outcomes among individuals diagnosed with connective tissue disease.Multi-parameter combined models incorporating echocardiographic variables can provide incremental predictive value compared with clinical models.

Purpose To investigate the predictive value of nomogram based on preoperative CT imaging for predicting programmed cell death receptor ligand 1(PD-L1)expression in patient with lung adenocarcinoma.Materials and Methods A total of 158 patients with lung adenocarcinoma were enrolled in Shenzhen people's Hospital from January 2021 to July 2022,of which 82 were negative for PD-L1 and 76 were positive for PD-L1.They were randomly divided into training set(n=119)and verification set(n=39)according to the proportion of 7:3.The significant characteristics between PD-L1 negative and PD-L1 positive were screened by univariate and multivariate Logistic regression to construct a clinical model.Radiomics features were extracted from preoperative CT images,and then features were screened and modeled.Finally,the combined model was established by clinical factors and radiomics features,which was visualized by nomogram.The diagnostic performance of the model was evaluated using receiver operating characteristic curves and area under the curve(AUC).Results The area under the curve(AUC)of the clinical model composed of carcinoembryonic antigen and vascular convergence sign was 0.774(95%CI 0.687-0.860)and 0.808(95%CI 0.670-0.947)in the training set and validation set,respectively.Through feature screening,the radiomics model was composed of 17 radiomics features,and the AUC of the training and validation sets was 0.837(95%CI 0.764-0.910)and 0.778(95%CI 0.633-0.923).The training set and validation set of the combined model composed of carcinoembryonic antigen,vascular convergence sign and radiomics score were AUC 0.892(95%CI 0.832-0.952)and 0.853(95%CI 0.737-0.968).In the training set,the AUC of the combined model was higher than that of the other two models(Z=-2.640,-2.855,P＜0.05).Conclusion Based on preoperative CT radiomics nomogram,it had high predictive efficacy on the expression of PD-L1 in lung adenocarcinoma and could provide decision-making support for the selection of clinical treatment regimens for lung adenocarcinoma patients.

Objective To compare the hematological parameters,biochemical profiles,histopathological characteristics,and cytokines associated with lipid metabolism in 8-weeks-old specific pathogen-free(SPF)grade and germ-free(GF)golden hamsters.Methods Twenty 8-weeks-old SPF grade and GF golden hamsters,with equal numbers of males and females,were utilized in this study.Serum cytokines associated with routine blood parameters,blood biochemistry,and lipid metabolism were quantified using automated hematology and biochemical analyzers,and enzyme-linked immunosorbent assay kits.The cecum,small intestine,lung,spleen,forestomach,and glandular stomach were examined by histopathology.Results We compared the result between SPF grade and GF golden hamsters at 8 weeks of age.Regarding hematological parameters,females showed significant differences(P＜0.05)in white blood cell count,hemoglobin concentration,mean corpuscular hemoglobin(MCH),and mean platelet volume between the two groups,and highly significant differences(P＜0.001)in MCH concentration(MCHC),platelet distribution width(PDW),and lymphocyte count(LYM).Males showed significant differences(P＜0.05)in mean corpuscular volume,MCH,LYM,neutrophil count,basophil count,and basophil percentage,and highly significant differences(P＜0.001)in MCHC,PDW,lymphocyte percentage,and neutrophil percentage.In terms of biochemical parameters,females showed significant differences(P＜0.05)in low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol,fasting insulin(FINS),and glycosylated serum protein(GSP),and highly significant differences(P＜0.001)in triglycerides(TG).Males showed significant differences(P＜0.05)in GSP levels and highly significant differences(P＜0.001)in total cholesterol,TG,LDL-C,FINS,and C-peptide levels.For serum cytokines related to lipid metabolism,females showed significant differences(P＜0.05)in interleukin(IL)-10,adiponectin(ADP),and IL-6 levels,and highly significant differences(P＜0.001)in high-sensitivity C-reactive protein(hs-CRP).Males showed significant differences(P＜0.05)in hs-CRP levels and highly significant differences(P＜0.001)in ADP and tumor necrosis factor-alpha levels.Hematoxylin/eosin staining showed that the cecal muscle layer was thinner and the number of crypts attached to the mucous membrane was reduced in GF compared with SPF grade golden hamsters.In addition,the ileocele was enlarged and the number of goblet cells was increased,the alveolar septum was widened,immune cells in the white pulp of the spleen were increased,and the blood content in the blood sinuses was increased.There was also thinning of the anterior gastric mucosa and the basophilic strength of the glandular gastric tube gland was weakened.Conclusions This study established the differences in routine blood parameters,blood biochemistry indicators,histopathological features,and cytokines associated with lipid metabolism between 8-weeks-old SPF grade and GF golden hamsters,to establish preliminary reference ranges.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects upper and lower motor neurons, and its mechanism has not been fully elucidated. In recent years, studies have shown that TAR DNA binding protein-43 (TDP-43) can affect neuronal function through multiple pathways and is closely related to the clinical manifestations and prognoses of ALS patients, suggesting that TDP-43 pathology may be an important target for the diagnosis and treatment of ALS. This article reviews the research progress on role of TDP-43 pathology in pathological mechanism of ALS and its application in diagnosis and treatment of ALS, aiming to provide reference for diagnosis and treatment of ALS.

Objective A sterile golden hamster model was established by cesarean section purification.Methods SPF-grade donor female golden hamsters were selected,and males and females were mated 1∶1 and separated after mating.The cage time of the surrogate mothers was 1 week earlier than that of the donor mothers.Parturient golden hamsters underwent hysterectomy on a sterilized workbench,and the uteruses were transferred into isolation kits and stripped.To obtain sterile milk for milk replacement,sterile ICR mice and sterile SD rats were used.After successful separation,the hamsters were transferred to isolation kits to prepare for feeding.The sterility status of the feeding isolation kits was tested monthly.Results Three caesarean sections were performed,but the first and second lactations failed.The third milk replacement was successful,and 18 young hamsters were obtained with survival rates of 88%and 66%after weaning.All hamsters were quality tested by GB/T 14926.41-2001.Conclusions Using a cesarean section purification technique and sterile ICR mice and SD rats for microbial-free milk replacement,a sterile golden hamster model was obtained.

Sonodynamic therapy is a novel treatment for killing malignant tumors with sonic sensitizers and low-intensity ultrasound,which via ultrasonic mechanical stress,the effects of ultrasonic cavitation and the combined production of ultrasound and acoustic sensitizers produce reactive oxygen species induces apoptosis co-destructing target cells.Compared with traditional approaches for the treatment of malignancy,sonodynamic therapy has advantages of greater accuracy,deeper tissue penetration,better patient dependency,and less side effects.Ultrasound microsphere contrast agents can significantly enhance the effects of cavitation as synthetic cavitation nuclei,and precise regulation of the effects of cavitation is a key factor in improving the efficiency of sonodynamic therapy.The combination of ultrasonic microspheres and adjustable cavitation have broad prospects in the field of sonodynamic therapy for malignant tumors.