This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

Objective:To explore the correlation between transcranial sonography (TCS) combined with serum homocysteine (Hcy), blood glucose, blood lipids, the cognitive status of Parkinson′s disease (PD) patients, and to analyze the clinical application value of these parameters in assessing the cognitive status of PD patients.Methods:A total of 152 PD patients admitted to the Second Affiliated Hospital of Soochow University from January 2020 to June 2023 were retrospectively collected as the PD group, and 101 healthy examinees matched for age and gender during the same period were selected as control group. Clinical data [age, gender, duration of illness, Montreal Cognitive Assessment (MoCA) score, Mini-Mental State Examination (MMSE) score, Unified Parkinson′s Disease Rating Scale Part Ⅲ (UPDRS-Ⅲ) score, Hoehn-Yahr (H-Y) stage, etc.], serum tests (Hcy, blood glucose, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein concentration), and TCS examination results (third ventricular width, midbrain area, peak systolic velocity of bilateral middle cerebral arteries, bilateral middle cerebral artery resistance index, bilateral substantia nigra hyperechoic area) were collected. The two groups were divided into pure PD group and PD group with elevated Hcy, pure control group and control group with elevated Hcy, based on an Hcy concentration threshold of ≥15 μmol/L. The differences in the above parameters among the four groups were compared. The correlation between Hcy and cognitive status (MoCA score, MMSE score) of PD patients and the above parameters were analyzed.Results:The MoCA score and MMSE score of the PD group with elevated Hcy were lower than those of the pure PD group, and the UPDRS-Ⅲ score and H-Y stage were higher than those of the pure PD group (all P<0.001). The order of Hcy concentration from high to low was PD group with elevated Hcy, pure Hcy elevation group, pure PD group, and pure control group. The differences in serum data and TCS data among the four groups were statistically significant (all P<0.001). Spearman correlation analysis showed: ①In the PD group, the concentration of Hcy was positively correlated with glucose concentration, H-Y stage, low-density lipoprotein concentration, right middle cerebral artery resistance index, UPDRS-Ⅲ score, total cholesterol concentration, triglyceride concentration, left middle cerebral artery resistance index, third ventricular width, and age ( rs=0.422, 0.350, 0.348, 0.334, 0.325, 0.300, 0.293, 0.283, 0.221, 0.164, all P<0.05); Hcy concentration was negatively correlated with midbrain area, MMSE score, MoCA score, peak systolic velocity of right middle cerebral artery, peak systolic velocity of left middle cerebral artery, and high-density lipoprotein concentration ( rs=-0.328, -0.282, -0.245, -0.229, -0.224, -0.192, all P<0.05). ②Clinical data, serum data, and TCS data of PD patients were all correlated with MoCA score and MMSE score, with midbrain area showing the largest positive correlation ( rs=0.524, 0.516; both P<0.05) and H-Y stage showing the largest negative correlation( rs=-0.490, -0.468; both P<0.05). Conclusions:PD patients with elevated Hcy have lower cognitive scores than pure PD patients. The correlation between Hcy concentration and blood glucose concentration is the highest in PD patients, followed by H-Y stage. The cognitive scores of PD patients are most correlated with midbrain area and unrelated to substantia nigra hyperechoic area. Lowering serum Hcy concentration in PD patients may be one of the ways to delay cognitive impairment.

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.

AIM To investigate the mechanism of triterpenoids quillaic acid and gypsogenin-3-O-glucuronide from Psammosilene tunicoides on tunicamycin-induced rheumatoid arthritis fibroblasts-like synoviocytes(RA-FLS)via the endoplasmic reticulum pathway.METHODS The research objects of tunicamycin-induced RA-FLS intervened with quillaic acid and gypsogenin-3-O-glucuronide had their cell proliferation activity detected;their level of tumor nerosis factor-α(TNF-α)detected by ELISA;their apoptosis detected by flow cytometry;their cell migration ability detected by Transwell experiment;their expressions of transcription activator 6(ATF-6),glucose regulatory protein 78(GRP78),C/EBP homologous protein(CHOP),cysteine protease protein-12(caspase-12)and anti-apoptosis Bcl-2 protein detected by Western blot;and their mRNA expressions of ATF-6,GRP78 and CHOP detected by RT-qPCR.RESULTS Compared with the model group,each group intervened with quillaic acid or gypsogenin-3-O-glucuronide displayed decreased levels of TNF-α(P＜0.01);weakened cell proliferation and migration ability(P＜0.01);increased apoptosis rate(P＜0.01);decreased protein expressions of ATF-6 and Bcl-2(P＜0.05,P＜0.01);and increased protein expressions of CHOP and caspase-12(P＜0.05,P＜0.01).In addition,decreased GRP78 protein expression in the low and medium dose groups(P＜0.05,P＜0.01);decreased mRNA expression of ATF-6,GRP78(P＜0.01)and increased CHOP mRNA expression(P＜0.01)in the medium dose groups of quillaic acid and gypsogenin-3-O-glucuronide were observed as well.CONCLUSION Quillaic acid and gypsogenin-3-O-glucuronide may play a protective role in rheumatoid arthritis by inhibiting the proliferation and migration of RA-FLS,inducing apoptosis and reducing the secretion of related inflammatory factors via endoplasmic reticulum signal pathway.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Objective: To investigate the distribution and characteristics of gene mutations in osteosarcoma, and to analyze the frequency and types of detectable mutations, and to identify potential targets for individualized treatment of osteosarcoma. Methods: The fresh tissue or paraffin-embedded tissue samples of 64 cases of osteosarcoma that were surgically resected or biopsied and then subject to next generation sequencing, were collected from Beijing Jishuitan Hospital, China from November 2018 to December 2021. The tumor DNA was extracted to detect the somatic and germline mutations using targeted sequencing technology. Results: Among the 64 patients, 41 were males and 23 were females. The patient age ranged from 6 to 65 years with a median age of 17 years, including 36 children (under 18 years old) and 28 adults. There were 52 cases of conventional osteosarcoma, 3 cases of telangiectatic osteosarcoma, 7 cases of secondary osteosarcoma, and 2 cases of parosteosarcoma. The detection rate of gene mutations was overall 84.4% (54/64). There were 324 variations in 180 mutated genes, including 125 genes with copy number variations, 109 single nucleotide variants, 83 insertions or deletions, and 7 gene fusions. The most common mutated genes were TP53, VEGFA, CCND3, ATRX, MYC, RB1, PTEN, GLI1, CDK4 and PTPRD. Among them, TP53 had the highest mutation rate (21/64, 32.8%), single nucleotide variant was the main mutation type (14/23, 60.9%), and 2 cases carried the TP53 germline mutation. VEGFA and CCND3 showed copy number amplification simultaneously in 7 cases. Conclusions: The high-frequency mutation of TP53 suggests that it plays an important role in the pathogenesis and development of osteosarcoma. VEGFA, CCND3 and ATRX are mutated genes in osteosarcoma and worthy of further studies. Combination of pathologic diagnosis and next generation sequencing with clinical practice can guide individualized treatment for patients with refractory, recurrent and metastatic osteosarcoma.
Adult ; Male ; Child ; Female ; Humans ; Adolescent ; Young Adult ; Middle Aged ; Aged ; DNA Copy Number Variations ; Osteosarcoma/pathology* ; Mutation ; DNA, Neoplasm ; High-Throughput Nucleotide Sequencing ; Bone Neoplasms/pathology* ; Nucleotides

Objective: To construct and verify a light-weighted convolutional neural network (CNN), and explore its application value for screening the early stage (subcategory 0/1 and stage Ⅰ of pneumoconiosis) of coal workers' pneumoconiosis (CWP) from digital chest radiography (DR) . Methods: A total of 1225 DR images of coal workers who were examined at an Occupational Disease Prevention and Control Institute in Anhui Province from October 2018 to March 2021 were retrospectively collected. All DR images were collectively diagnosed by 3 radiologists with diagnostic qualifications and gave diagnostic results. There were 692 DR images with small opacity profusion 0/- or 0/0 and 533 DR images with small opacity profusion 0/1 to stage Ⅲ of pneumoconiosis. The original chest radiographs were preprocessed differently to generate four datasets, namely 16-bit grayscale original image set (Origin16), 8-bit grayscale original image set (Origin 8), 16-bit grayscale histogram equalized image set (HE16) and 8-bit grayscale histogram equalized image set (HE8). The light-weighted CNN, ShuffleNet, was applied to train the generated prediction model on the four datasets separately. The performance of the four models for pneumoconiosis prediction was evaluated on a test set containing 130 DR images using measures such as the receiver operating characteristic (ROC) curve, accuracy, sensitivity, specificity, and Youden index. The Kappa consistency test was used to compare the agreement between the model predictions and the physician diagnosed pneumoconiosis results. Results: Origin16 model achieved the highest ROC area under the curve (AUC=0.958), accuracy (92.3%), specificity (92.9%), and Youden index (0.8452) for predicting pneumoconiosis, with a sensitivity of 91.7%. And the highest consistency between identification and physician diagnosis was observed for Origin16 model (Kappa value was 0.845, 95%CI: 0.753-0.937, P<0.001). HE16 model had the highest sensitivity (98.3%) . Conclusion: The light-weighted CNN ShuffleNet model can efficiently identify the early stages of CWP, and its application in the early screening of CWP can effectively improve physicians' work efficiency.
Humans ; Retrospective Studies ; Anthracosis/diagnostic imaging* ; Pneumoconiosis/diagnostic imaging* ; Coal Mining ; Neural Networks, Computer ; Coal

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Aged ; Antiviral Agents/therapeutic use* ; COVID-19/drug therapy* ; China/epidemiology* ; Cohort Studies ; Female ; Hospital Mortality ; Hospitalization ; Humans ; Male ; Middle Aged ; Patient Acuity ; SARS-CoV-2 ; Treatment Outcome