Abstract Alzheimer′s disease(AD) is a common neurodegenerative disease. It has been found that AD is related to various pathogenic factors such as genetics, cardiovascular and cerebrovascular disease, and excessive phosphorylation of tau protein. However, no definitive conclusions on its pathogenesis have been reached. In this paper, the research progress on the pathogenesis of AD inC.elegansmodel and the therapeutic effects of traditional Chinese medicine extracts on AD are reviewed, providing a basis for further research on the alleviating effects of Chinese medicine extracts on AD.

BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

With the main pathological features of glomerulosclerosis and interstitial fibrosis， renal fibrosis is a key pathological process causing chronic kidney disease to progress to end-stage disease. As a cellular autophagic process， mitochondrial autophagy plays a crucial role in maintaining mitochondrial mass and functional stability. Mitochondrial dysfunction is considered to be one of the key factors driving the progression of fibrosis. Phosphatase and tension protein homologue （PTEN） induce various signalling pathways such as putative kinase 1/parkin， Nip3-like protein X/Bcl-2 interacting protein 3， and FUN14 structural domain-containing protein 1 to activate mitochondrial autophagy to participate in the regulation of fibrogenic factors， amelioration of oxidative stress， and inhibition of inflammatory response and apoptosis， which in turn effectively slows down the progression of renal fibrosis. Studies have shown that traditional Chinese medicine monomers and compound preparations， including phenolics， terpenoids， ketones， and alkaloids， can regulate mitochondrial autophagy-related signalling pathways and achieve significant clinical efficacy in intervening in the progression of renal fibrosis for the treatment of chronic kidney disease. This paper summarized the mechanism of mitochondrial autophagy and the research progress of traditional Chinese medicine intervention in renal fibrosis to provide new ideas for the study of the mechanism of traditional Chinese medicine in treating renal fibrosis.

With the main pathological features of glomerulosclerosis and interstitial fibrosis， renal fibrosis is a key pathological process causing chronic kidney disease to progress to end-stage disease. As a cellular autophagic process， mitochondrial autophagy plays a crucial role in maintaining mitochondrial mass and functional stability. Mitochondrial dysfunction is considered to be one of the key factors driving the progression of fibrosis. Phosphatase and tension protein homologue （PTEN） induce various signalling pathways such as putative kinase 1/parkin， Nip3-like protein X/Bcl-2 interacting protein 3， and FUN14 structural domain-containing protein 1 to activate mitochondrial autophagy to participate in the regulation of fibrogenic factors， amelioration of oxidative stress， and inhibition of inflammatory response and apoptosis， which in turn effectively slows down the progression of renal fibrosis. Studies have shown that traditional Chinese medicine monomers and compound preparations， including phenolics， terpenoids， ketones， and alkaloids， can regulate mitochondrial autophagy-related signalling pathways and achieve significant clinical efficacy in intervening in the progression of renal fibrosis for the treatment of chronic kidney disease. This paper summarized the mechanism of mitochondrial autophagy and the research progress of traditional Chinese medicine intervention in renal fibrosis to provide new ideas for the study of the mechanism of traditional Chinese medicine in treating renal fibrosis.

Objective·To investigate the application effects and benefits of full-neuroendoscopic technique in the surgical treatment of posterior cranial fossa lesions.Methods·A retrospective analysis was conducted on the clinical data of 105 patients with posterior cranial fossa lesions who underwent surgery using full-neuroendoscopic techniques at the Department of Neurosurgery,Renji Hospital,Shanghai Jiao Tong University School of Medicine,between January 2021 and December 2023.The data included patients'gender,age,lesion locations,nature of lesions,surgical procedures,and postoperative recovery.Follow-up with contrast-enhanced MRI was performed one month postoperatively,with subsequent follow-ups every three months on average,depending on the nature of the lesions.Results·Among the 105 patients,there were 45 males with an average age of(56±17)years and 60 females with an average age of(62±12)years.Lesions were predominantly located in the cerebellopontine angle area(78 cases),with others in the petrous bone area(7 cases),cerebellum(10 cases),and brainstem(10 cases).The nature of lesions included vestibular schwannoma(11 cases),meningioma(7 cases),glioma(7 cases),brain metastases(7 cases),hemangioblastoma(6 cases),cyst(1 case),and neuropathic conditions such as trigeminal neuralgia(43 cases),hemifacial spasm(22 cases),and glossopharyngeal neuralgia(1 case).All patients successfully underwent resection or biopsy of their lesions or microvascular decompression under full-neuroendoscopy.The follow-up period ranged from 3 months to 3 years.Enhanced MRI confirmed complete resection in 34 tumor cases(87.2％),near-total resection in 3 cases(7.7％),and biopsy in 2 cases(5.1％).Three deaths occurred during follow-up.Among the patients with vascular neuropathic diseases,two with trigeminal neuralgia experienced incomplete pain relief postoperatively.The resolution rates for hemifacial spasm and glossopharyngeal neuralgia were 100％.Postoperative complications occurred in 3 cases,with 2 cases of hydrocephalus that were managed with ventriculoperitoneal shunting,and 1 case of poor wound healing.Conclusion·Full-neuroendoscopic technique demonstrates potential in the surgical treatment of posterior cranial fossa lesions.

Objective To establish a foot-weightlifting shoe coupling model,investigate the biomechanical effects of midsole material variations during pull phase of the snatch,optimize the key parameters of weightlifting shoes,and reduce the risk of foot and ankle injuries in athletes.Methods The foot-weightlifting shoe finite element model was constructed using the finite element method for simulation.Kinematic and dynamic data of the snatch movement were obtained using the sports biomechanics methods.Statistical methods were employed to validate the effectiveness of the model and compare the impact of different midsole materials on foot stress distribution,bone stress,soft tissue stress,and midsole strain of the athletes during pull phase of the snatch.Results When the midsole thermoplastic polyurethane(TPU)had an elastic modulus of 20 MPa,the peak foot stress was minimized.As the elastic modulus of the midsole TPU increased,the foot peak stress also increased.Bone stress was concentrated in the third,fourth,and fifth metatarsals of the forefoot,with the fourth metatarsal showing the peak stress.As the elastic modulus of the midsole increased,the peak stress in the metatarsal area gradually decreased,the peak stress in soft tissues gradually increased,and the strain in midsole decreased.Conclusions Medium-hardness midsole materials(with an elastic modulus between 20-25 MPa)have an advantage in reducing foot pressure and preventing bone injuries in the foot and ankle.

Objective To establish a foot-weightlifting shoe coupling model,investigate the biomechanical effects of midsole material variations during pull phase of the snatch,optimize the key parameters of weightlifting shoes,and reduce the risk of foot and ankle injuries in athletes.Methods The foot-weightlifting shoe finite element model was constructed using the finite element method for simulation.Kinematic and dynamic data of the snatch movement were obtained using the sports biomechanics methods.Statistical methods were employed to validate the effectiveness of the model and compare the impact of different midsole materials on foot stress distribution,bone stress,soft tissue stress,and midsole strain of the athletes during pull phase of the snatch.Results When the midsole thermoplastic polyurethane(TPU)had an elastic modulus of 20 MPa,the peak foot stress was minimized.As the elastic modulus of the midsole TPU increased,the foot peak stress also increased.Bone stress was concentrated in the third,fourth,and fifth metatarsals of the forefoot,with the fourth metatarsal showing the peak stress.As the elastic modulus of the midsole increased,the peak stress in the metatarsal area gradually decreased,the peak stress in soft tissues gradually increased,and the strain in midsole decreased.Conclusions Medium-hardness midsole materials(with an elastic modulus between 20-25 MPa)have an advantage in reducing foot pressure and preventing bone injuries in the foot and ankle.

Objective·To investigate the application effects and benefits of full-neuroendoscopic technique in the surgical treatment of posterior cranial fossa lesions.Methods·A retrospective analysis was conducted on the clinical data of 105 patients with posterior cranial fossa lesions who underwent surgery using full-neuroendoscopic techniques at the Department of Neurosurgery,Renji Hospital,Shanghai Jiao Tong University School of Medicine,between January 2021 and December 2023.The data included patients'gender,age,lesion locations,nature of lesions,surgical procedures,and postoperative recovery.Follow-up with contrast-enhanced MRI was performed one month postoperatively,with subsequent follow-ups every three months on average,depending on the nature of the lesions.Results·Among the 105 patients,there were 45 males with an average age of(56±17)years and 60 females with an average age of(62±12)years.Lesions were predominantly located in the cerebellopontine angle area(78 cases),with others in the petrous bone area(7 cases),cerebellum(10 cases),and brainstem(10 cases).The nature of lesions included vestibular schwannoma(11 cases),meningioma(7 cases),glioma(7 cases),brain metastases(7 cases),hemangioblastoma(6 cases),cyst(1 case),and neuropathic conditions such as trigeminal neuralgia(43 cases),hemifacial spasm(22 cases),and glossopharyngeal neuralgia(1 case).All patients successfully underwent resection or biopsy of their lesions or microvascular decompression under full-neuroendoscopy.The follow-up period ranged from 3 months to 3 years.Enhanced MRI confirmed complete resection in 34 tumor cases(87.2％),near-total resection in 3 cases(7.7％),and biopsy in 2 cases(5.1％).Three deaths occurred during follow-up.Among the patients with vascular neuropathic diseases,two with trigeminal neuralgia experienced incomplete pain relief postoperatively.The resolution rates for hemifacial spasm and glossopharyngeal neuralgia were 100％.Postoperative complications occurred in 3 cases,with 2 cases of hydrocephalus that were managed with ventriculoperitoneal shunting,and 1 case of poor wound healing.Conclusion·Full-neuroendoscopic technique demonstrates potential in the surgical treatment of posterior cranial fossa lesions.

Objective:To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy.Methods:A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results:Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG ( χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG ( χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion:Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.

Objective To examine the possible factors affecting the attainment of target serum trough concentration of vancomycin in premature newborns for optimization of clinical dosing regimens.Methods The vancomycin trough concentration data were collected retrospectively from preterm newborns who received intravenous infusion of vancomycin from December 2016 to March 2021.According to the Evidence-based Guideline for Therapeutic Drug Monitoring of Vancomycin:2020 Update by the Division of Therapeutic Drug Monitoring,Chinese Pharmacological Society,the patients were assigned to failure(＜5 mg/L)or success(5-15 mg/L)in target attainment,or beyond target group(＞15 mg/L)base on vancomycin trough concentration.Statistical software SPSS was used to analyze differences in clinical characteristics between different groups,and profile various factors that may affect attainment of target serum trough concentration of vancomycin.Results The median(interquartile range)trough concentration of vancomycin was 12.50(7.95-18.05)mg/L in 82 preterm newborns.The target trough concentration of vancomycin was attained in 47 preterm newborns(57.32％),and the corresponding trough concentration of vancomycin was 10.90(7.80-13.30)mg/L.The trough concentration of vancomycin was beyond target in 27 preterm newborns(32.93％).The corresponding median trough concentration of vancomycin was 21.80(18.00-23.80)mg/L.Serum trough concentration of vancomycin failed to achieve the target in only 8 preterm newborns(9.75％).The corresponding median trough concentration was 4.10(2.48-4.60)mg/L.Univariate analysis showed that there were statistically significant differences(P＜0.05)in postmenstrual age and current weight between the patients succeeded in attaining target trough concentration and those who failed to attain the target.Baseline serum creatinine and dosing interval showed statistically significant differences(P＜0.01)between the newborns who attained the target concentration and those with higher trough concentration beyond the target.Multivariate regression analysis showed that baseline serum creatinine(OR=1.063,95％CI 1.024-1.102,P=0.001,cutoff:62 pmol/L)and dosing interval(OR=6.693,95％CI 1.604-27.920,P=0.009)were independent risk factors for excessively high vancomycin trough concentrations.Conclusions The dosing regimens as recommended in the current package insert only enable the attainment of target serum trough concentration of vancomycin in half of the premature newborns.The dosing regimen of vancomycin should be optimized by taking postmenstrual age,current weight,baseline serum creatinine and dosing interval into account.Therapeutic drug monitoring is necessary to ensure safety and effectiveness.