ObjectiveTo clarify whether epigallocatechin gallate （EGCG） is involved in the clearance of amyloid β-protein （Aβ） and autophagy induction by microglia， so as to explore the potential mechanisms of EGCG in the prevention and treatment of Alzheimer's disease （AD）. MethodsSix-month-old APP/PS1 mice were randomly divided into model and EGCG groups， with some additional wild type （WT） mice as the control group， each group consisting of 15 mice. The EGCG group received continuous gavage administration［5 mg/（kg·d）］ for 8 weeks， followed by the open field test and Y-maze to assess the learning and memory abilities of the mice. Thioflavin-S staining was used to evaluate the content and distribution of amyloid β-protein （Aβ）in the brain parenchyma of the mice， and immunofluorescence was employed to detect the expression levels of Aβ_1-42， glial fibrillary acidic protein （GFAP）， and ionized calcium-binding adapter molecule 1 （Iba1） in the hippocampal tissue of the mice. Additionally， N9 mouse microglial cells were induced with 20 µmol/L Aβ_1-42， and the cell viability was measured after treatment with different concentrations of EGCG （5 µmol/L， 10 µmol/L， 20 µmol/L）. Western blotting was used to detect the levels of Aβ_1-42， low density lipoprotein receptor-related protein 1（LRP1）， receptor for advanced glycation endproducts （RAGE）， amyloid precursor protein （APP）， insulin degrading enzyme （IDE）， neprilysin （NEP）， microtubule associated protein 1 hydrogen chain 3（LC3）-Ⅱ/LC3-Ⅰ， phosphatidylinositol 3-hydroxy kinase（PI3K）， p-PI3K， protein kinase B （AKT）， p-AKT， mammalian target of rapamycin （mTOR）， p-mTOR， and histone deacetylase 6（HDAC6）. Finally， through the co-culture of microglial cells and neuronal SH-SY5Y cells， cell viability and Caspase-3 levels were measured to verify the protective effect of EGCG-mediated Aβ clearance on neurons. ResultsEGCG increased the activity time and frequency of APP/PS1 mice in the central area of the open field （P<0.05）， and enhanced the percentage of alternation in the Y-maze test （P<0.01）； EGCG reduced Aβ deposition in the hippocampal tissue of APP/PS1 mice and increased the number of microglia； in vitro experiments showed that EGCG improved the survival rate of Aβ-induced N9 cells （P<0.01）， upregulated RAGE activity （P<0.05）， and promoted the internalization and phagocytosis of Aβ （P<0.01）. ECGC activated microglial autophagy by downregulating the level of HDAC6 （P<0.05）， inhibiting the phosphorylation of PI3K， AKT， mTOR （P<0.001）， and increasing the LC3-Ⅱ/LC3-I ratio （P<0.001）； EGCG improved the survival rate of SH-SY5Y cells （P<0.05） and reduced the activity of Caspase-3 （P<0.01） by clearing Aβ_1-42 through microglia， and had a protective effect on neurons. ConclusionEGCG activates microglial autophagy to clear Aβ by targeting and inhibiting the HDAC6-PI3K/AKT/mTOR axis.

To implement the Opinions of the State Council of the Central Committee of the Communist Party of China on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine， delve into the diseases specifically responding to traditional Chinese medicine （TCM）， and serve the building of advantageous specialties， clinical talent cultivation， national research layout， and academic innovation， the Chinese Association of Chinese Medicine sponsored the salons in multiple fields to discuss the diseases specifically responding to TCM. On August 26， 2023， the 25^th salon on the diseases specifically responding to TCM was held in Shanghai. In view of the advantages of TCM and integrated traditional Chinese and Western medicine in the diagnosis and treatment of psoriasis， Chinese and western medicine experts and interdisciplinary researchers carried out extensive and in-depth discussions and formed specific suggestions and consensus on the diagnosis and treatment of psoriasis with TCM and integrated traditional Chinese and Western medicine. However， there was still a lack of detailed research path. Under the guidance of the Chinese Association of Chinese Medicine， this paper analyzes the problems in the diagnosis and treatment of psoriasis from the occurrence and development of psoriasis. According to the advantages and characteristics of TCM and integrated traditional Chinese and Western medicine in the diagnosis and treatment of psoriasis， this paper puts forward the main points of research layout for psoriasis from the three aspects of psoriasis diagnosis and treatment， comorbidity prevention， and chronic disease management as follows： ① optimization of the syndrome differentiation system for psoriasis， ② optimization of assessment indicators for psoriasis， ③ recurrence mechanisms of psoriasis， ④ construction and research of TCM prevention and treatment of psoriasis recurrence， ⑤ construction of the comorbidity spectrum and TCM theoretical system of psoriasis， ⑥ comorbidity mechanisms of psoriasis. Furthermore， this article proposed the research layout and directions， expected goals and values， and funding priorities. Therefore， on the basis of the series of salons about psoriasis as a disease specifically responding to TCM， this article puts forward the research paradigm of psoriasis， aiming to facilitate the high-quality development of TCM and provide reference for the national research layout， the research and development of new TCM preparations， the selection of research topics， and the formulation of guidelines and consensus.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans ; Male ; Prostatitis/blood* ; Adult ; Pelvic Pain/blood* ; Metabolomics ; Prostate/metabolism* ; Middle Aged ; Chronic Pain/blood* ; Metabolome ; Case-Control Studies ; Tryptophan/blood* ; Depression/blood* ; Oxidative Stress/physiology* ; Chronic Disease ; Lipid Metabolism/physiology*

OBJECTIVE: To investigate the correlation between platelet alloantibodies and CD8⁺ T cell with platelet desialylation and apoptosis in platelet transfusion refractoriness(PTR). METHODS: The expression of RCA-1, CD62P and Neu1 on platelets were detected in 135 PTR patients and 260 healthy controls. The ability of PTR patients' sera with anti-HLA antibody, anti-CD36 antibody and antibody-negative groups to induce platelet desialylation and apoptosis, and the potential effect of FcγR inhibitors on desialylation and apoptosis were evaluated. Additionally, the association between CD8⁺ T cells and platelet desialylation in patients was analyzed. RESULTS: The expression of RCA-1 and Neu1 on platelets in PTR patients were significantly higher than those in healthy donors（P < 0.05）, but were not related to platelet alloantibody (P >0.05). The sera of PTR patients generally induced platelet desialylation in vitro （P < 0.05）, with no significant differences among the groups（P >0.05）. However, the sera with anti-CD36 antibodies could induce platelet apoptosis significantly higher than that in the anti-HLA antibody group and antibody-negative group in vitro (P < 0.05). In PTR patients with anti-CD36 antibodies, platelet apoptosis was dependent on FcγR signaling, while desialylation is not. Moreover, CD8⁺ T cells in PTR patients were significantly associated with platelet desialylation (P < 0.05). CONCLUSION Platelet desialylation is a common pathological phenomenon in PTR patients， which involves the participation of CD8⁺ T cell, but isn't associated with platelet alloantibody; while anti-CD36 antibodies have potential clinical significance in predicting platelet apoptosis in PTR patients.
Humans ; Apoptosis ; CD8-Positive T-Lymphocytes/immunology* ; Blood Platelets/metabolism* ; Platelet Transfusion ; Isoantibodies ; Male ; Female ; Middle Aged

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective: To explore the regulatory effects of ginkgo biloba extract on airway inflammatory injury and Toll⁃like receptor 4(TLR4)/nucleotide⁃binding oligomerization domain⁃containing 3(NLRP3) pathway in rats with vided into four groups : the normal control group , Methods: Thirty⁃six male SD rats were selected and randomly divided into four groups : the normal control group , the model group , the prednisone treatment group , and the ginkgo biloba extract treatment group , with 9 rats in each group. Except for the normal control group , the COPD rat mod⁃els in the other groups was constructed by intratracheal instillation of lipopolysaccharide (LPS) combined with ciga⁃rette smoke exposure. After successful modeling , the rats were continuously administered drugs for 12 weeks , fol⁃lowed by sampling. The general conditions and respiratory symptoms of the rats were observed. The pathological changes of lung tissues were observed by hematoxylin⁃eosin (HE) staining technique ; the mRNA and protein ex⁃pression levels of TLR4 , tumor necrosis factor⁃α (TNF⁃α ) , interleukin⁃1β (IL⁃1β) and NLRP3 in rat lung tissueswere detected by real⁃time quantitative polymerase chain reaction (RT⁃qPCR) and Western blot. Results: Com⁃pared with the normal control group , the lung tissues of rats in the model group were significantly damaged , and the protein and mRNA expression of TLR4 , TNF⁃α , IL⁃1β , and NLRP3 increased ( P < 0. 05 ) . Compared with the model group , lung tissue damage was reduced in the prednisone group and the ginkgo biloba extract group , and TLR4 , TNF⁃α , IL⁃1β , NLRP3 protein and mRNA expression decreased (P < 0. 05) . Conclusion Ginkgo biloba airway inflammatory response by inhibiting the TLR4/NLRP3 signaling pathway.

Objective:To search and summarize the best evidence for preoperative prehabilitation in patients with lung cancer complicated by chronic obstructive pulmonary disease and to inform the management of preoperative prehabilitation in patients with lung cancer combined with COPD by clinical providers.Methods:Systematically guideline websites, professional society websites, evidence-based databases, and comprehensive databases were searched for types of literature including clinical decision making, guidelines, expert consensus, evidence summaries, systematic evaluations, Meta-analyses, and randomized controlled trials. The time for the retrieval was from the inception of databases until October 31th, 2023. And the quality of the included literature was evaluated and evidence was extracted, evaluated the quality of the included literature, and extracted evidence.Results:Finally, 18 articles were included, including 8 guidelines, 8 expert consensus, and 2 systematic reviews. Summarized the 30 best evidence in 4 areas of prerehabilitation: need, timing, location, content (including smoking cessation management, respiratory exercise, exercise, nutritional support, and medication management).Conclusions:This study summarizes the best evidence for preoperative prehabilitation in patients with lung cancer combined with chronic obstructive pulmonary disease, and healthcare professionals should be mindful of the need to develop preoperative prehabilitation protocols judiciously, taking into account the specific clinical context during the subsequent translation of the evidence to the clinic.

Objective:To detect the expression level of tRF-31-PER8YP9LON4VD in the serum of breast cancer patients and to explore its effect on the function of breast cancer cells.Methods:The serums of 57 breast cancer patients, 39 breast benign tumor patients and 40 normal physical examination patients in the Affiliated Cancer Hospital of Nanjing Medical University from April to August in 2022 were collected. Real-time quantitative polymerase chain reaction(RT-qPCR) to detect the expression level of tRF-31-PER8YP9LON4VD in breast cancer cell lines and serum of breast cancer patients. Cell invasion assay, migration assay and CCK-8 proliferation assay were used to analyze the effect of tRF-31-PER8YP9LON4VD on breast cancer cell function. The receiver operating characteristic curve (ROC) curve was used to analyze the diagnostic efficacy of tRF-31-PER8YP9LON4VD in serum in breast cancer. The chi-square test was used to analyze the correlation between tRF-31-PER8YP9LON4VD and clinical features.Results:The expression levels of tRF-31-PER8YP9LON4VD in breast cancer cell lines MDA-MB-231 (0.50±0.22 vs 1.00±0.01), T-47D (0.33±0.02 vs 1.00±0.01) and MCF-7 (0.50±0.02 vs 1.00±0.01) were significantly lower than those in normal mammary epithelial cell lines (1.00±0.01), and the difference was statistically significant (all P<0.05). The expression level of tRF-31-PER8YP9LON4VD in the serum of breast cancer patients (1.35±1.25) was lower than that in the serum of patients with normal physical examination (6.42±3.13) and patients with benign breast tumors (9.57±2.11), and the difference was statistically significant (both P<0.001). Compared with the control group, the invasiveness of overexpressing tRF-31-PER8YP9LON4VD T-47D (86.67±12.22 vs 532.00±22.68, P<0.001) and MDA-MB-231 (535.33±99.12 vs 1 055.67±24.00, P=0.002) was weaker, and that of T-47D (442.67±81.79 vs 1 210.67±115.02, P=0.002) and MDA-MB-231 (278.67±108.40 vs 571.33±95.37, P=0.015) had weaker migration ability, and T-47D and MDA-MB-231 had weaker proliferative ability (all P<0.05). The area under the curve of serum tRF-31-PER8YP9LON4VD for the diagnostic efficacy of breast cancer was 0.743 (95% CI 0.644-0.842), and the sensitivity and specificity were 89.50% and 53.10%, respectively. Conclusion:tRF-31-PER8YP9LON4VD is low expressed in the serum of breast cancer patients, and it may inhibit the proliferation, migration and invasion of breast cancer cells.

BACKGROUND:Studies have shown that imbalance of bone metabolism during glucocorticoid-induced osteonecrosis of the femoral head necrosis is closely related to oxidative stress. OBJECTIVE:To investigate the pathological mechanism by which oxidative stress-induced ferroptosis promote apoptosis in osteoblasts involved in steroid-induced osteonecrosis of the femoral head. METHODS:General data and serum specimens were collected from 47 patients with steroid-induced osteonecrosis of the femoral head.In addition,six femoral head specimens were collected from these patients.According to the Association Research Circulation Osseous(ARCO)staging system,serum specimens were grouped into ARCO Ⅱ,Ⅲ,and IV,while femoral head specimens were classified into ARCO Ⅲ and IV.Serum levels of malondialdehyde and superoxide dismutase 1 were measured.The protein expression of superoxide dismutase 1,glutathione peroxidase 4,Bcl-2 in the femoral head was detected and verified by Data independent acquisition(DIA)for quantitative sequencing,western blot and alkaline phosphate detection. RESULTS AND CONCLUSION:The ARCO stage of patients with steroid-induced osteonecrosis of the femoral head was independent of age,sex and necrotic side.The serum levels of malondialdehyde and superoxide dismutase 1 were higher in patients with ARCO stage Ⅲ compared with those with ARCO stage Ⅱ and IV.The results of DIA protein quantification showed that the function of differential proteins was mainly related to redox.The levels of superoxide dismutase 1,glutathione peroxidase 4,and Bcl-2 in the necrotic region were lower than in the normal region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.Western blot verified the results of DIA protein quantification.The alkaline phosphatase activity was lower in the necrotic region than in the normal region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.In the necrotic and sclerotic regions,the function of differential proteins was also related to redox,and superoxide dismutase 1,glutathione peroxidase 4,Bcl-2 protein expression and alkaline phosphatase activity were lower in the necrotic area than in the sclerotic region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.To conclude,glucocorticoids can influence the progression of steroid-induced osteonecrosis of the femoral head by upregulating oxidative stress levels,inducing osteoblast ferroptosis,and inhibiting osteogenic function.

Objective: To examine the developmental trajectory of fine motor ability in schoolage children with attention deficit hyperactivity disorder (ADHD) for two years, so as to provide scientific evidence to promote motor development in ADHD children. Methods: From April to June 2019, 31 children aged 6-8 years old were selected from a public elementary school. They were diagnosed with ADHD by two psychiatric professionals according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. Additionally, 31 typical developmental children, matched for age, sex and IQ with the ADHD group, were recruited as the control group. Fine motor ability was assessed with tasks of hand manual dexterity in Movement Assessment Battery for Children-2 (MACB-2), and a followup assessment was conducted from April to June 2021. The development changes of fine motor ability between two groups of children were compared by using t test and repeated measures analysis of variance. Results: Between baseline and followup periods after two years, the total score of hand fine motor in the ADHD group did not show significant improvement (7.4±3.0, 8.0±3.4; t=-1.05, P>0.05), while there was a small effect size improvement in typically developing control group (9.5±2.1, 10.5±2.4; t=-2.12, effect size=0.38, P<0.05). Followup after two years, coin/peg throwing scores with dominant hand improved between ADHD group and control group (7.0±3.3, 9.5±3.2; 8.4±2.8, 11.6±1.6) (t=-3.74, -6.33, P<0.01; effect size=0.67, 1.14), with a smaller improvement in the ADHD group. The score for threading beads/threads decreased in between ADHD group and control group (7.9±2.4, 5.8±3.1; 9.2±1.1, 8.2±1.9) (t=3.89, 2.78, P<0.01; effect size=0.70, 0.50), with a greater decrease in the ADHD group. Conclusions The development speed of fine motor ability in children with ADHD aged 6-8 is slow and continues to lag behind normal developmental children. Fine motor development in children with ADHD should be closely monitored, and targeted interventions should be implemented when necessary.