Research on immune checkpoints such as programmed death protein-1(PD-1)and cytotoxic T lymphocyte antigen-4(CTLA-4)has provided new directions for tumor treatment.V-domain immunoglobulin suppressor of T-cell activation(VISTA)is an emerging immune checkpoint within the B7 family.Functioning as both a ligand and a receptor,VISTA is an inhibitory immune checkpoint molecule expressed in tumor cells,myeloid cells and T lymphocytes.It plays a crucial role in regulating autoimmunity,inflammatory response and tumor immunity.The non-redundant interactions between VISTA and other immune checkpoints,such as PD-1,may offer new therapeutic strategies and serve as a new target for overcoming immunotherapy resistance.This review summarizes the recent research progress on VISTA in hematological tumors,aiming to provide new insights into its application in the treatment of these malignancies.

Objective To establish a method based on high performance liquid chromatography for the determination of 3-demethylcolchicine(3 DMC)in rat plasma and to study its pharmacokinetic behavior in rats.Methods The concentration of 3 DMC in rat plasma was determined by high performance liquid chromatography(HPLC).Plasma samples were precipitated by acetonitrile and supernatant was centrifuged for analysis.The determination conditions were as follows:The chromatography was performed on Alphasil VC-C18 column(4.6 mm × 150.0 mm,5.0 μm)with mobile phase consisted of water-acetonitrile-methanol(79∶16∶5),iso-elution at the flow rate of 0.8 mL·min-1.The detection wavelength was set at 240 nm,with polydacryin as the internal standard.The specificity,standard curve and lower limit of quantitation,precision and recovery,matrix effect and stability of the method were investigated.The rats were randomly divided into low,medium and high dose groups(1,2 and 4 mg·kg-1 3DMC were injected into the tail vein,respectively),and blood was collected from orbital venous plexus.The concentration of 3DMC in plasma samples was measured;the pharmacokinetic parameters were calculated using Drug And Statistics(DAS)2.0.Results 3DMC has a good linear relationship between 0.39 and 25.00 μg·mL-1,and its standard curve is y=5.96 × 10-2x+7.60 × 10-3(r=0.999 5).The lower limit of quantitation was 0.39 μg·mL-1,the intra-day and inter-day relative standard deviations were-5.08％to 0.75％,the recovery was 93.23％to 108.90％,the matrix effect was 94.88％to 104.00％,and the stability relative standard deviation(RSD)was less than 8.72％.All the results met the requirements.Pharmacokinetic parameters of low,medium and high dose groups:Cmax were(1.66±0.24),(4.36±0.78)and(9.73±1.42)mg·L-1,respectively;t1/2 were(0.31±0.02),(0.32±0.11)and(0.48±0.06)h,respectively;AUC0-t were(0.50±0.09),(1.53±0.16)and(2.67±0.11)mg·L-1·h,respectively.Conclusion The established method for the determination of 3DMC concentration in rat plasma is simple,specific and sensitive,and is suitable for the determination of 3DMC concentration and pharmacokinetic study in rat plasma.

Objective To establish a method based on high performance liquid chromatography for the determination of 3-demethylcolchicine(3 DMC)in rat plasma and to study its pharmacokinetic behavior in rats.Methods The concentration of 3 DMC in rat plasma was determined by high performance liquid chromatography(HPLC).Plasma samples were precipitated by acetonitrile and supernatant was centrifuged for analysis.The determination conditions were as follows:The chromatography was performed on Alphasil VC-C18 column(4.6 mm × 150.0 mm,5.0 μm)with mobile phase consisted of water-acetonitrile-methanol(79∶16∶5),iso-elution at the flow rate of 0.8 mL·min-1.The detection wavelength was set at 240 nm,with polydacryin as the internal standard.The specificity,standard curve and lower limit of quantitation,precision and recovery,matrix effect and stability of the method were investigated.The rats were randomly divided into low,medium and high dose groups(1,2 and 4 mg·kg-1 3DMC were injected into the tail vein,respectively),and blood was collected from orbital venous plexus.The concentration of 3DMC in plasma samples was measured;the pharmacokinetic parameters were calculated using Drug And Statistics(DAS)2.0.Results 3DMC has a good linear relationship between 0.39 and 25.00 μg·mL-1,and its standard curve is y=5.96 × 10-2x+7.60 × 10-3(r=0.999 5).The lower limit of quantitation was 0.39 μg·mL-1,the intra-day and inter-day relative standard deviations were-5.08％to 0.75％,the recovery was 93.23％to 108.90％,the matrix effect was 94.88％to 104.00％,and the stability relative standard deviation(RSD)was less than 8.72％.All the results met the requirements.Pharmacokinetic parameters of low,medium and high dose groups:Cmax were(1.66±0.24),(4.36±0.78)and(9.73±1.42)mg·L-1,respectively;t1/2 were(0.31±0.02),(0.32±0.11)and(0.48±0.06)h,respectively;AUC0-t were(0.50±0.09),(1.53±0.16)and(2.67±0.11)mg·L-1·h,respectively.Conclusion The established method for the determination of 3DMC concentration in rat plasma is simple,specific and sensitive,and is suitable for the determination of 3DMC concentration and pharmacokinetic study in rat plasma.

Humans ; Blast Crisis/genetics* ; Leukemia, Promyelocytic, Acute/genetics* ; Oncogene Proteins, Fusion/genetics* ; Tretinoin

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

Respiratory infectious diseases (RID) are the major public health problems threatening the people's lives and health.Infection control (IC) is one of the effective tools to contain the occurrence and spread of RID.We collected the articles and data on IC published since January 1,2018 and summarized the achievements,problems,and challenges of IC from administrative control,management control,environment and engineering control,and personal protection in the medical institutions and public places in China.The efforts for IC vary in different regions and medical institutions of different levels.There are still links to be improved for IC from administrative control,management control,environment and engineering control,and personal protection,especially in community-level medical institutions and public areas.It is urgent to strengthen the implementation of IC policies and conduct IC precisely according to local situations.We proposed the following suggestions.First,the existing IC products and tools should be applied to precisely implement the IC measures;second,modern high technology should be employed to develop efficient and convenient IC products and tools;finally,a digital or intelligent IC platform should be built for monitoring infections,so as to contain the occurrence and spread of RID.
Humans ; COVID-19 ; Infection Control ; Communicable Diseases ; China/epidemiology*

Aim To predict the key targets and signaling pathways of Semiliquidambar cathayen. sis Chang (JLBFH) by network pharmacology and molecular docking,etc, then to explore the mechanism of JLBFH' s effect on inflammatory response to depression through reserpine-induced depression rat model. Methods The target of drug and disease was predicted by network pharmacological database, protein interaction network diagram was constructed, biofunctional enrichment and pathways were analyzed, and molecular docking prediction was performed by AGFR software. Based on reserpine-induced depression, the role of JLBFH in depression inflammation was verified by behavior, molecular biology and pathological examination, and so on. Results A total of 13 active ingredients were screened, 11 key targets of JLBFH modulation of depression were selected, and the bioenrichment results were mainly related to cognition, prominent plasticity regulation, etc. The pathways were mainly related to Rapl signaling pathway, Toll-like receptor signaling pathways. The results of validation experiments showed that high and low doses of JLBFH extract significantly shortened the forced swimming immobility time in mice, markedly reduced the retention time in the circle of rats, increased serum levels of 5-HT and DA, decreased serum levels of IL-6, improved inflammatory infiltration in the prefrontal cortex, decreased brain tissue levels of IL-6,IL-1β ,TNF-α mRNA expression,and increased AKT1 mRNA expression in brain tissue. Conclusions The present study reveals that JLBFH can exert antidepressant effects through multi-component, multi-target and multi-pathway, and the experimental validation results show that JLBFH can improve the d¬pression-like symptoms by improving the inflammatory response of depression through TOLL-like signaling pathway.

This study was aimed at understanding the genome-wide characterization and variations for three imported novel coronavirus(SARS-CoV-2)strains from different sources in the same period in Jinan at the viral genome level,to provide a sci-entific basis for further improving the prevention and control of COVID-19 outbreaks at Jinan port.We selected nasal and pha-ryngeal swab samples from three cases of imported asymptomatic COVID-19infectionat Jinan port;performed second-genera-tion whole-genome sequencing;and analyzed the variant loci and homology withvarious bioinformatics software.The whole ge-nome sequence of SARS-CoV-2 was successfully obtained from three samples of asymptomatic infected cases,and had full lengths ranging from 29 835 bp to 29 844 bp.Pangolin typing results indicated that the genotypes of the three samples were O-micron BQ.1,BQ.1.1,and BQ.1.12.Compared with the original Wuhan strain,the three samples produced mutations at 77,80,and 78 base sites,respectively,involving 60-63 non-synonymous mutations,mainly in the S and ORF1ab genes.Omicron BQ.1 is an imported variant of the SARS-CoV-2 virus and was detected for the first time at Jinan port.From a molecular biolo-gy perspective,this study provides a theoretical basis for the source tracing and prevention and control of COVID-19 at theport.

This study aims to identify the active components and the mechanism of Jingqi Yukui Capsules(JQYK) in the treatment of gastric ulcer based on network pharmacology, and verify some key targets and signaling pathways through animal experiment. To be specific, first, the active components and targets of JQYK were retrieved from a Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets of gastric ulcer from GeneCards and Online Mendelian Inheritance in Man(OMIM) with the search term "gastric ulcer". The common targets of the two were the potential targets of the prescription for the treatment of the di-sease. Then, protein-protein interaction(PPI) network of key targets were constructed based on STRING and Cytoscape 3.7.2, followed by Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by matescape database and pathway visualization by Omicshare. For the animal experiment, the improved method of Okabe was used to induce gastric ulcer in rats, and the model rats were classified into the model group, JQYK high-dose(JQYK-H), medium-dose(JQYK-M), and low-dose(JQYK-L) groups, Anweiyang Capsules(WYA) group, and Rabeprazole Sodium Enteric Capsules(RBPZ) group. Normal rats were included in the blank group. Rats in the blank group and model group were given distilled water and those in the administration groups received corresponding drugs. Then gastric ulcer healing in rats was observed. The changes of the gastric histomorphology in rats were evaluated based on hematoxylin-eosin(HE) staining, and the content of inducible nitric oxide synthase(iNOS) in rat gastric tissue was detected with Coomassie brilliant blue method. The mRNA and protein levels of some proteins in rat gastric tissue were determined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot(WB) to further validate some key targets and signaling pathways. A total of 206 active components and 535 targets of JQYK, 1 305 targets of gastric ulcer, and 166 common targets of the disease and the drug were yielded. According to PPI analysis and KEGG pathway enrichment analysis, multiple key targets, such as interleukin-6(IL-6), tumor necrosis factor(TNF), mitogen-activated protein kinase 1(MAPK1), MAPK3, and MAPK14, as well as nuclear factor kappa-B(NF-κB) signaling pathway, IL-17 signaling pathway, and leukocyte transendothelial migration in the top 20 key signaling pathways were closely related to inflammation. The key protein p38 MAPK and NF-κB signaling pathway were selected for further verification by animal experiment. The gastric ulcer in the JQYK-H group recovered nearly to the level in the blank group, with significant decrease in the content of iNOS in rat gastric tissue and significant reduction in the mRNA and phosphorylation levels of p38 MAPK and the mRNA and protein levels of NF-κB p65 in rat gastric tissue. The results indicated that JQYK can inhibit the phosphorylation of the key protein p38 MAPK and the expression of NF-κB p65 in the NF-κB signaling pathway, thereby exerting the anti-inflammatory effect and effectively improving the quality of gastric ulcer healing in rats. Thus, the animal experiment result verifies some predictions of network pharmacology.
Animal Experimentation ; Animals ; Capsules ; Gastric Mucosa/metabolism* ; Humans ; Network Pharmacology ; Rats ; Stomach Ulcer/genetics*

Recent advancement in natural language processing (NLP) and medical imaging empowers the wide applicability of deep learning models. These developments have increased not only data understanding, but also knowledge of state-of-the-art architectures and their real-world potentials. Medical imaging researchers have recognized the limitations of only targeting images, as well as the importance of integrating multimodal inputs into medical image analysis. The lack of comprehensive surveys of the current literature, however, impedes the progress of this domain. Existing research perspectives, as well as the architectures, tasks, datasets, and performance measures examined in the present literature, are reviewed in this work, and we also provide a brief description of possible future directions in the field, aiming to provide researchers and healthcare professionals with a detailed summary of existing academic research and to provide rational insights to facilitate future research.
Humans ; Natural Language Processing ; Surveys and Questionnaires