Aim To research the neuroprotective effect of Haikun Shenxi (HKSX) medicated serum on N2a/ App695 cells and the underlying mechanism. Methods HKSX medicated serum was prepared and carbohydrate components in it was analyzed using high performance thin layer chromatography (HPTLC) . N2a/ App695 cells were intervened with HKSX medicated serum, the cytotoxicity of HKSX medicated serum was measured by MTT; AP[_

Type 2 diabetes mellitus(T2DM)is associated with an increased incidence rate of cardiovascular disease(CVD).In recent years,numerous cardiovascular outcome trials(CVOT)have confirmed the definite cardiovascu-lar benefits of glucagon-like peptide-1 receptor agonists(GLP-1RA).In this paper,the existing GLP-1RAs were summarized,with special attention to their clinical impact on cardiovascular disease risk factors and mechanism of action,so as to provide theoretical basis for clinical prevention and treatment of CVD,and provide more treat-ment options not only for T2DM patients complicated with CVD,but also for non-diabetic patients.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To investigate the causal correlation between depression and stress urinary incontinence(SUI)using Mendelian randomization(MR)analysis.Methods:We searched the FinnGen Consortium database for genome-wide association studies(GWAS)on depression and obtained 23 424 case samples and 192 220 control samples,with the GWAS data on SUI provided by the UK Biobank,including 4 340 case samples and 458 670 control samples.We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium(PGC).We employed inverse-variance weighting as the main method for the MR study,and performed sensitivity analysis to verify the accuracy and stability of the findings.Results:Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI(P=0.005),but not SUI with the risk of depression(P=0.927).And analysis of the PGC data verified the correlation of depression with the increased risk of SUI(P=0.043).Conclusion:Depression is associated with an increased risk of SUI,while SUI does not increase the risk of depression.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

As an indicator that measures the degree of implementation of intervention measures during the implementation process, fidelity could be used for monitoring and quality evaluation of the completion degree of intervention measures, and plays an important role in improving the degree of intervention implementation and clarifying the factors that affect intervention implementation. This article aims to introduce the connotation and significance, measurement, control, and current application status of fidelity, as well as the current application status of fidelity in acupuncture-moxibustion clinical research and its inspiration for future research. Meanwhile, based on the existing evaluation tool development methods of fidelity and the characteristics of acupuncture-moxibustion clinical research, a preliminary fidelity evaluation framework is proposed. Introducing fidelity into acupuncture-moxibustion clinical research could improve the implementation quality and compliance of acupuncture-moxibustion in clinical research, increase the credibility and effectiveness of clinical research results, and promote the transformation of acupuncture-moxibustion experience into easily learnable and promotable treatment plans.
Moxibustion ; Acupuncture Therapy

The present study aimed to explore the main active components and underlying mechanisms of Marsdenia tenacissima in the treatment of ovarian cancer(OC) through network pharmacology, molecular docking, and in vitro cell experiments. The active components of M. tenacissima were obtained from the literature search, and their potential targets were obtained from SwissTargetPrediction. The OC-related targets were retrieved from Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man(OMIM), GeneCards, and PharmGKB. The common targets of the drug and the disease were screened out by Venn diagram. Cytoscape was used to construct an "active component-target-disease" network, and the core components were screened out according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened out according to the node degree. GO and KEGG enrichment analyses of potential therapeutic targets were carried out with DAVID database. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock. Finally, the anti-OC activity of M. tenacissima extract was verified based on SKOV3 cells in vitro. The PI3K/AKT signaling pathway was selected for in vitro experimental verification according to the results of GO function and KEGG pathway analyses. Network pharmacology results showed that 39 active components, such as kaempferol, 11α-O-benzoyl-12β-O-acetyltenacigenin B, and drevogenin Q, were screened out, involving 25 core targets such as AKT1, VEGFA, and EGFR, and the PI3K-AKT signaling pathway was the main pathway of target protein enrichment. The results of molecular docking also showed that the top ten core components showed good binding affinity to the top ten core targets. The results of in vitro experiments showed that M. tenacissima extract could significantly inhibit the proliferation of OC cells, induce apoptosis of OC cells through the mitochondrial pathway, and down-regulate the expression of proteins related to the PI3K/AKT signaling pathway. This study shows that M. tenacissima has the characteristics of multi-component, multi-target, and multi-pathway synergistic effect in the treatment of OC, which provides a theoretical basis for in-depth research on the material basis, mechanism, and clinical application.
Humans ; Female ; Marsdenia ; Molecular Docking Simulation ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Ovarian Neoplasms/genetics* ; Databases, Genetic ; Plant Extracts ; Drugs, Chinese Herbal/pharmacology*

AIM: To analyze the changes of serum homocysteine(Hcy), vitamin B12(VitB12)and folic acid in the serum of patients with diabetic retinopathy(DR), and to explore their significance in the occurrence and development of DR.METHODS: A case-control study was designed. A total of 95 patients with DR(DR group), 94 patients with diabetes mellitus(DM group)treated in endgcrinology department and 87 patients with age-related cataract(normal control group)from the ophthalmology department of Shenzhen People's Hospital between July 2021 and January 2022 were selected. Fasting venous blood was collected and serum was separated. The concentration of Hcy in serum was detected by enzyme linked immunosorbent assay(ELISA), and chemiluminescence immunoassay was used to detect the concentration of VitB12 and folic acid. Pearson linear correlation analysis was used to evaluate the correlation between Hcy and clinical parameters. Multivariate linear regression analysis was used to evaluate the main factors which affect Hcy level. Receiver operating characteristic(ROC)curve was designed to analyze the diagnostic value of serum Hcy, VitB12 and folic acid in DR.RESULTS: The concentration of serum Hcy in DR group was 16.52±3.54 μmol/L, which was significantly higher than that in DM group(10.86±3.47 μmol/L)and control group(6.84±1.39 μmol/L; all P<0.05); The concentration of VitB12 in the serum of the control group was 501.79±108.95 pmol/L, which was higher than that in DM group(478.57±57.85 pmol/L)and DR group(455.88±181.49 pmol/L), but the difference was not statistically significant(P=0.054); The concentration of folic acid in serum of control group was 10.31±2.43 nmol/L, which was higher than that of DM group(9.94±1.90 nmol/L)and DR group(7.27±2.79 nmol/L), and the difference between DR group and DM group was statistically significant(P<0.05); In DR group, Hcy expression was weakly positively correlated with triglyceride and low density lipoprotein(r=0.208, P=0.043; r=0.240, P=0.019). Multivariate linear regression showed that low density lipoprotein was an important factor which affect the expression of Hcy in DR patients. ROC curve shows that Hcy has important value in the diagnosis of DR.CONCLUSIONS: Hcy, VitB12 and folic acid are differentially expressed in DR group, DM group and normal control group. Hcy may be involved in the pathogenesis of DR, and it has important value in the diagnosis of DR. In addition, low density lipoprotein is also an important factor which affects the expression of Hcy.

Psoriasis is a non-infectious chronic inflammatory skin disease. It′s acknowledged that interleukin (IL)-17 signaling pathway dominantly drives the development of psoriasis. Recently, the role of neuro-immune axis in psoriasis has attracted widespread attention. Lidocaine, a local anesthetic, has ability to block the conduction of nerve impulses, while its therapeutic efficacy on psoriasis remains to be confirmed. Here, we evaluated the therapeutic efficacy of topical application of compound lidocaine cream (LIDO) on imiquimod (IMQ)-induced mouse psoriasis model. Animal welfare and experimental procedures follow the regulations of the Ethics Committee of China Pharmaceutical University. The psoriasis area and severity index (PASI) scoring was used to evaluate the severity of psoriasis-like symptoms. Hematoxylin-eosin staining was used to examine histopathological changes and epidermal thickness was measured. Ki67 immunofluorescence staining was used to evaluate the proliferation of keratinocytes. The relative mRNA expression of inflammatory cytokines (including Il17, Il22, Il23 and Il36) in skin was measured by real-time quantitative PCR. Results show that IMQ-induced increases in the PASI score, epidermal thickness, number of Ki67⁺ cells and the mRNA expression of inflammatory cytokines are significantly alleviated by topical application of LIDO, whose therapeutic efficacy is also better than that of the positive control drug calcipotriol. Our study suggests that LIDO could be used for psoriasis treatment.