Objective To evaluate the advantages of powder-liquid double-chamber bag products compared with traditional powder injection. Methods The systematic review method was used to collect the literature on powder-liquid double-chamber bag, extract common evaluation indicators, evaluate the use value of powder-liquid double-chamber bag products, and conduct a comprehensive comparison with traditional powder injection products. Results A total of 23 articles were included in the literature. The effectiveness indicators used for evaluation were the stability of the liquid medicine, the accuracy of the preparation concentration, and the residual amount of the liquid medicine; the safety indicators were the incidence of insoluble particles and the incidence of punctures and scratches. The economic indicators were preparation cost, occupied volume of preparation supplies, waste weight, hospitalization cost and incidence of blood infection. The applicability indicators were preparation time, average occupation of medical staff, packaging weight and storage and transportation volume, environmental adaptability, and ease of waste disposal. Accessibility indicators are the number of manufacturers, raw material supply capacity, and patient affordability. Through the evaluation of literature evidence, it was found that the stability and concentration accuracy of the powder-liquid double-chamber bag were higher than those of the traditional powder injection, and the domestic supply had been achieved. The double-chamber bag method can reduce the infusion reaction and shorten the preparation time of the liquid medicine. Conclusion Compared with traditional powder injectabler products, powder-liquid double-chamber bags have advantages in the dimensions of effectiveness, safety, economy, suitability and innovation, and the accessibility dimension meets the requirements.

Objective : To construct a molecular classification system for head and neck squamous cell carcinoma (HNSCC) utilizing hypoxia-related gene (HAG) expression profiles, and to comprehensively examine the clinicopathological significance and biological functions of the hypoxia gene stanniocalcin 2 (STC2) in HNSCC. Methods : Transcriptomic data and clinical information of 546 HNSCC samples were obtained from The Cancer Genome Atlas (TCGA) database, and based on the expression profiles of 200 HRGs, HNSCC was classified subclasses using non-negative matrix factorization (NMF). HNSCC was classified into three subclasses (C1, C2, and C3), and the molecular characteristics and prognostic differences of the subclasses were assessed by comparing the tumor mutation load, functional enrichment analysis, drug sensitivity, and clinical features among the subclasses. LASSO-Cox regression was used to screen prognosis-related genes and construct prognostic models. Using oral squamous cell carcinoma (OSCC)-related data in the TCGA database, we analyzed the expression differences of STC2 in OSCC and control samples, and detected the mRNA and protein expression of STC2 in oral squamous carcinoma samples using qRT-PCR and immunohistochemistry. We knocked down STC2 in CAL-27 cells and verified the knockdown efficiency by qRT-PCR and Western blot. CCK-8 assay and cell scratch assay were used to assess the effect of STC2 on cell proliferation and migration ability. Results: Based on HRGs expression profiles, HNSCC was categorized into three subclasses (C1, C2, and C3). Subclass C1 had moderate hypoxic activity and good prognosis; subclass C2 had the highest hypoxic activity, poor prognosis, and poor sensitivity to CTLA-4 inhibitors (P<0.05); subclass C3 had the lowest hypoxic activity and moderate prognosis, and STC2 belonged to subclass C3. The frequency of cyclin-dependent kinase inhibitor 2A (CDKN2A), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and tumor protein p53 (TP 53) mutations was higher in HNSCC. C1 genomic gain and deletion burden were significantly higher than C3 subclass (P<0.05) and C2 genomic gain than C3 subclass (P<0.05). The C2 subclass was significantly enriched in hypoxia-associated pathways, such as glycine metabolism and base excision repair (P<0.05). The C1, C2, and C3 subclasses were significantly positively correlated in terms of sex (male) (Cramer’s V=0.15), radiation exposure (Cramer’s V=0.12), medication (Cramer’s V=0.18), and pathological grading (G1/G2) (Cramer’s V=0.25) (P<0.05). Nine prognosis-related genes were screened by LASSO-Cox regression, among which high expression of STC2 was positively correlated with poorer overall survival (OS) in HNSCC patients (P<0.01). Bioinformatics analysis showed that STC2 mRNA expression was higher in OSCC than in normal controls (P<0.05). qRT-PCR and immunohistochemistry confirmed that both mRNA and protein expression of STC2 were significantly upregulated in OSCC tissues and cells (P<0.01). In vitro experiments showed that STC2 expression was knocked down to approximately 80% in CAL-27 cells (P<0.001), and the STC2 knockdown group had a reduced value-added rate (P<0.001) and a reduced percentage of scratch closure (P<0.05) compared with the control group. Conclusion We successfully constructed a molecular typing system for HNSCC based on the expression profiles of HRGs and categorized HNSCC into three subclasses with significant prognostic differences, among which the C2 subclass had the highest hypoxic activity and the poorest prognosis. STC2 was highly expressed in HNSCC and suggested a poor prognosis, demonstrating that it may be a potential target for HNSCC treatment.

Objective To analyze the prevalence status of cardiometabolic risk factor (CMRF) and its aggregation among workers engaged in new forms of employment. Methods A total of 5 429 new employment workers (including couriers, online food delivery workers, and ride hailing drivers) who underwent health medical examinations at a tertiary hospital in Beijing City were selected as the research subjects using the judgment sampling method. Data on waist circumference, blood pressure, blood glucose, and blood lipid levels were collected to analyze their CMRF [central obesity, elevated blood pressure, elevated blood glucose, elevated triglycerides, and reduced high-density lipoprotein cholesterol (HDL-C)] and their aggregation (with ≥ 2 of the above 5 risk factors) status. Results The detection rates of central obesity, elevated blood pressure, elevated blood glucose, elevated triglycerides, and reduced HDL-C were 61.2%, 38.2%, 29.5%, 40.9% and 22.6%, respectively. The detection rates of CMRF aggregation was 57.8%. The result of multivariable logistic regression analysis showed that male, age ≥45 years, smoking, overweight, and obesity were risk factors for CMRF aggregation (all P<0.05). Conclusion The detection rate of CMRF and its aggregation among workers with new forms of employment in Beijing City is relatively high. Targeted prevention and control efforts should be strengthened for high-risk populations, especially males, workers aged ≥45 years, smokers, and those who are overweight or obese.

Dysregulation of immune response is currently recognized as one of the important pathological factors in ulcerative colitis (UC). Based on the confirmation that the Sini San (SNS) can significantly improve the colon inflammation induced by dextran sulfate sodium sulfate (DSS) in mice, the present work systematically studied the xenobiotics in the colon and mesenteric lymph nodes, spleen, and thymus of UC mice after administration of SNS by high-performance liquid chromatography-ion trap time-of-flight mass spectrometry (HPLC-IT-TOF-MS). The results showed that, in addition to the colon, some components and their metabolites in SNS could be distributed in immune tissues, and it was found that the quality of relatively low-abundance and weakly responsive components such as saikosaponin a, paeoniflorin, and glycyrrhizic acid had the characteristics of efficient transmission to the colon and lymphoid organs. These components were very likely to be the source of pharmacodynamic substances of SNS. The findings of this study lay a foundation for the study of the efficacy and molecular mechanism of the components against ulcerative colitis, and also provide a scientific basis for the rational clinical application of SNS, which is expected to promote the secondary development of its preparations.

OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G₁-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation ; Matrix Metalloproteinase 9 ; Molecular Docking Simulation ; Cell Cycle ; ErbB Receptors ; Apoptosis ; Colorectal Neoplasms/pathology* ; Cell Line, Tumor

Objective To preliminarily investigate the anti-tumor effects of phytosphingosine(PHS)and the involvement of inducing apoptosis of leukemia cells.Methods Cellular model of leukemia was established in leukemia cell lines K562 and SUP-B15.CCK-8 assay and EdU assay were used to measure the viability and DNA synthesis of K562 and SUP-B15 cells.RNA-seq was carried out to verify the differentially expressed genes(DEGs)after PHS treatment.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were applied to analyze the involved functions and signaling pathways.Comparative Toxicogenomics Database(CTD)and Discovery Studio software were employed to predict the underlying targets of PHS and molecular docking.Cell apoptosis was detected by flow cytometry,mitochondrial membrane potential was evaluated by JC-1 probe,and protein expression of key molecules was validated by Western blotting.Results PHS inhibited the proliferation of K562 and SUP-B15 cells in a time-and dose-dependent manner.The half-maximal inhibitory concentration(IC50)of K562 cells was 17.67 and 12.52 pmol/L for 24 and 48 h,respectively,and the IC50 value of SUP-B15 cells was 17.58 and 14.86 μmol/L for 24 and 48 h,respectively.PHS treatment at a dose of 20 μmol/L for 48 h resulted in significant inhibition of DNA synthesis.GO enrichment analysis of the K562 cells showed that PHS might be involved in positive regulation of apoptotic process,plasma membrane and its integral components,and protein kinase binding and activity.Reverse predictive analysis showed that BCL-2 protein was the most likely target of PHS.PHS significantly increased the apoptotic rate of leukemia cells(P＜0.05)in a dose-dependent manner,reduced the mitochondrial membrane potential,and down-regulated BCL-2 level(P＜0.05)and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9(P＜0.05).Conclusion PHS may inhibit the proliferation of leukemia cells by inducing mitochondria-dependent apoptosis,possibly through PHS and BCL-2 interaction.

A liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was developed for determination of three kinds of β-agonists(Clenbuterol(CL),Ractopamine(RAC)and Salbutamol(SAL))residues in animal liver samples.The liver sample homogenates were extracted with organic solvent,followed by clean-up using the automatic magnetic solid-phase extraction(MSPE),and then analyzed using LC-MS/MS.The results showed that the magnetic mixed-mode cation exchange adsorbent(M-MCX)exhibited 34%higher adsorption capacity than the conventional mixed-mode cation exchange(MCX)column.Furthermore,the clean-up was conducted by using an automatic MSPE device,and 8 samples could be simultaneously treated within 30 min.The limits of detection(LOD)were 0.01-0.1 μg/kg,the average recoveries ranged from 88.2%to 110.5%,and the relative standard deviations(RSDs)were in range of 2.9%-10.3%at three spiked levels for the three kinds of β-agonists.Compared with the traditional SPE technique,the present method had many advantages such as simple operation,rapidity and high efficiency,which was suitable for high-throughput and automatic detection of residues in routine analysis.