Cell models can simulate a variety of life states and disease developments, including single cells, two-dimensional (2D) cell cultures, three-dimensional (3D) multicellular spheroids, and organoids. They are essential tools for addressing complex biochemical questions. With continuous advancements in biological and cellular analysis technologies, in vitro cellular models designed to answer scientific questions have evolved rapidly. Early in vitro models primarily relied on 2D systems, which failed to accurately replicate the complex cellular compositions and microenvironmental interactions observed in vivo, let alone support sophisticated investigations into cellular biological functions. Subsequent improvements in cell culture techniques led to the development of 3D culture-based models, such as cellular spheroids. The advent of pluripotent stem cell technology further advanced the development of organoid systems, which closely mimic human organ development. Compared to traditional 2D models, both 3D cellular models and organoids offer significant advantages, including personalization and enhanced physiological relevance, making them particularly suitable for exploring molecular mechanisms of disease progression, discovering novel cellular and biomolecular functions, and conducting related studies. The imaging analysis of common cellular models primarily employs labeling-based methods for in situ imaging of targeted genes, proteins, and small-molecule metabolites, enabling further research on cell types, states, metabolism, and drug efficacy. However, these approaches have drawbacks such as poor labeling specificity and complex experimental procedures. By using cells as experimental models, mass spectrometry technology combined with morphological analysis can reveal quantitative changes and spatial distributions of various biological substances at the spatiotemporal level, including metabolites, proteins, lipids, peptides, drugs, environmental pollutants, and metals. This allows for the investigation of cell-cell interactions, tumor microenvironments, and cellular bioinformational heterogeneity. The application of these cutting-edge imaging technologies generates vast amounts of cellular data, necessitating the development of rapid, efficient, and highly accurate image data algorithms for precise segmentation and identification of single cells, multi-organelle structures, rare cell subpopulations, and complex cellular morphologies. A critical focus lies in creating deep learning models and algorithms that enhance the accuracy of cellular visualization. At the same time, establishing more robust data integration tools is essential not only for analyzing and interpreting outputs but also for effectively uncovering the biological significance of spatially resolved mass spectrometry data. Developing a cell imaging platform with high versatility, operational stability, and specificity to enable data interoperability will significantly enhance its utility in clinical research, thereby advancing investigations into disease molecular mechanisms and supporting precision diagnostics and therapeutics. In contrast to genomic, transcriptomic, and proteomic information, the metabolome can rapidly respond to external stimuli and cellular physiological changes within a short timeframe. This rapid and precise reflection of ongoing cellular state alterations has positioned spatial metabolomics as a pivotal approach for exploring the molecular mechanisms underlying physiological and pathological processes in cells, tissues, and organisms. In this review, we summarize research on cell imaging based on mass spectrometry technologies, including the selection and preparation of cell models, morphological analysis of cell models, spatial omics techniques based on mass spectrometry, mass cytometry, and their applications. We also discuss the current challenges and propose future directions for development in this field.

OBJECTIVE To provide practical basis and policy recommendations for improving the pharmacovigilance （PV） system construction in medical institutions across China. METHODS A questionnaire survey was conducted using a mixed sampling strategy of “online random sampling+offline supplementary sampling” to distribute questionnaires among pharmaceutical professionals in tertiary medical institutions nationwide. The questionnaire covered aspects such as the construction of PV systems， job position settings， information system support， operational practices， and multi-stakeholder collaboration. The data were analyzed using descriptive methods and SPSS 20.0 statistical software. RESULTS A total of 70 valid questionnaires were collected from 66 medical institutions， primarily Class A tertiary hospitals. The survey found that 90.00% had designated PV personnel and 74.29% routinely conducted PV activities. However， there were notable disparities in resource allocation and information system capacity， with less than 50% of the institutions conducting post-marketing drug re-evaluation. PV activities were primarily focused on the collection and reporting of adverse drug reactions， with limited capabilities in signal detection and risk assessment. CONCLUSIONS Among the surveyed tertiary hospitals， PV systems have begun to take shape. However， challenges persist in terms of system establishment， resource allocation， risk assessment， and inter-organizational coordination. Policy efforts should focus on strengthening regulatory frameworks， improving information sharing mechanisms， enhancing professional training， and strengthening collaboration between hospitals and market authorization holders to ensure the effective implementation of PV in medical institutions.

This paper explains the mechanism of the mutual switching between physiological sleep and wakefulness from the aspects of the sleep circadian system and the sleep homeostasis system. In the circadian rhythm system, with the suprachiasmatic nucleus as the core, the anatomical connections between the suprachiasmatic nucleusand various systems that affect sleep are summarized, starting from the suprachiasmatic nucleus, passing through the four pathways of the melatonin system, namely, subventricular area of the hypothalamus, the ventrolateral nucleus of the preoptic area, orexin neurons, and melatonin, then the related mechanisms of their regulation of sleep and wakefulness are expounded. In the sleep homeostasis system, with adenosine and prostaglandin D2 as targets, the role of hypnogen in sleep arousal mechanisms in regulation is also expounded.

Glucagon-like peptide-1 ( GLP-1 ) is secreted by gut enteroendocrine cells. GLP-1 receptor agonists ( GLP-1 RAs) control glucose-related augmentation of insulin and suppress glu-cagon secretion. GLP-lRAs also inhibit gastric emptying, food intake and limit weight gain. In the past decade, significant progresses have been made in the investigation on the effects of GLP-1 RAs on cardiovascular system. The potential advantages of oral small-molecule GLP-1 RAs could improve the application of this class of drugs. This review highlights the multiple cardiovascular profiles of GLP-1 RAs in the treatment of cardiovascular diseases to provide new insights into cardiovascular benefits of GLP-1 RAs.

Objective To investigate the effect of non-alcoholic fatty liver disease(NAFLD)induced by high-fat diet(HFD)on the kidneys of mice and the protective effect and mechanism of Xiayuxue Decoction.Methods A total of 25 healthy controls and 25 NAFLD patients who attended Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from September 2020 to September 2021 were enrolled,and the levels of total cholesterol(TC),triglyceride(TG),blood urea nitrogen(BUN),creatinine(Cr),and uric acid(UA)were measured.A total of 24 male C57BL/6 mice were randomly divided into low-fat diet(LFD)group,HFD group,and HFD+Xiayuxue Decoction group(XYXD group),with 8 mice in each group,and since week 13,XYXD was administered by gavage once a day for 6 weeks till the end of week 18.The level of TC,TG,BUN,and Cr were measured for each group.HE staining and oil red staining were used to observe the pathological changes of the liver and the kidneys;immunohistochemical double staining was used to measure the expression levels of CD68 and alpha-smooth muscle actin(α-SMA);quantitative real-time PCR was used to measure the expression levels of sterol regulatory element binding protein 1(SREBP1),fatty acid synthase(FASN),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),Desmin,and α-SMA in renal tissue;Western blot was used to measure the protein expression levels of SREBP1 and TNF-α.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for pairwise comparison;the independent-samples t-test was used for comparison between two groups.Results Compared with the healthy controls,NAFLD patients showed significant increases in the levels of TC,TG,BUN,Cr,and UA(all P<0.05).Compared with the LFD group,the HFD group had significant increases in body weight,TC,TG,BUN,and Cr(all P<0.001),and compared with the HFD group,the XYXD group showed significant inhibition of the expression of TC,TG,BUN,and Cr(all P<0.001).Liver pathological examination showed that compared with the LFD group,the HFD group showed significant increases in hepatic steatosis and inflammatory infiltration,while the XYXD group showed significant alleviation of lesions.Renal pathological examination showed that compared with the LFD group,the HFD group had significant inflammatory infiltration,steatosis,and collagen formation in renal tissue,and compared with the HFD group,XYXD significantly alleviated inflammatory infiltration and inhibited steatosis and collagen formation.Quantitative real-time PCR showed that compared with the LFD group,the HFD group had significant increases in the relative mRNA expression levels of SREBP1,FASN,IL-6,TNF-α,Desmin,and α-SMA in renal tissue(all P<0.001),and compared with the HFD group,the XYXD group had significant reductions in the relative expression levels of these indicators(all P<0.001).Western blot showed that compared with the LFD group,the HFD group had significant increases in the protein expression levels of SREBP1 and TNF-α(P<0.05),and compared with the HFD group,the XYXD group had significant reductions in the protein expression levels of SREBP1 and TNF-α(P<0.05).Immunohistochemical staining showed that compared with the LFD group,the HFD group had significant increases in the positive staining or the double positive staining of α-SMA and CD68(P<0.05),and compared with the HFD group,the XYXD group showed significant reductions(P<0.05).Conclusion HFD can induce renal steatosis,inflammatory infiltration,and collagen formation,and XYXD might exert a protective effect on the kidneys by inhibiting the expression of macrophages and myofibroblasts in renal tissue.

Objective As primary Sj?gren's syndrome(pSS)primarily affects the salivary glands,saliva can serve as an indicator of the glands'pathophysiology and the disease's status.This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis. Methods The discovery set contained 49 samples(24 from pSS and 25 from age-and gender-matched healthy controls[HCs])and the validation set included 25 samples(12 from pSS and 13 from HCs).Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio.Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition(DIA)strategy on a 2D LC-HRMS/MS platform to reveal differential proteins.The crucial proteins were verified using DIA analysis and annotated using gene ontology(GO)and International Pharmaceutical Abstracts(IPA)analysis.A prediction model for SS was established using random forests. Results A total of 1,963 proteins were discovered,and 136 proteins exhibited differential representation in pSS patients.The bioinformatic research indicated that these proteins were primarily linked to immunological functions,metabolism,and inflammation.A panel of 19 protein biomarkers was identified by ranking order based on P-value and random forest algorichm,and was validated as the predictive biomarkers exhibiting good performance with area under the curve(AUC)of 0.817 for discovery set and 0.882 for validation set. Conclusions The candidate protein panel discovered may aid in pSS diagnosis.Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients.DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective To evaluate the predictive value of global longitudinal strain(GLS)measured by cardiac magnetic resonance(CMR)feature-tracking technique for left ventricular remodeling(LVR)after percutaneous coronary intervention(PCI)in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A total of 403 patients undergoing PCI for acute STEMI were prospectively recruited from multiple centers in China.CMR examinations were performed one week(7±2 days)and 6 months after myocardial infarction to obtain GLS,global radial strain(GRS),global circumferential strain(GCS),ejection fraction(LVEF)and infarct size(IS).The primary endpoint was LVR,defined as an increase of left ventricle end-diastolic volume by≥20%or an increase of left ventricle end-systolic volume by≥15%from the baseline determined by CMR at 6 months.Logistic regression analysis was performed to evaluate the predictive value of CMR parameters for LVR.Results LVR occurred in 101 of the patients at 6 months after myocardial infarction.Compared with those without LVR(n=302),the patients in LVR group exhibited significantly higher GLS and GCS(P<0.001)and lower GRS and LVEF(P<0.001).Logistic regression analysis indicated that both GLS(OR=1.387,95%CI:1.223-1.573;P<0.001)and LVEF(OR=0.951,95%CI:0.914-0.990;P=0.015)were independent predictors of LVR.ROC curve analysis showed that at the optimal cutoff value of-10.6%,GLS had a sensitivity of 74.3%and a specificity of 71.9%for predicting LVR.The AUC of GLS was similar to that of LVEF for predicting LVR(P=0.146),but was significantly greater than those of other parameters such as GCS,GRS and IS(P<0.05);the AUC of LVEF did not differ significantly from those of the other parameters(P>0.05).Conclusion In patients receiving PCI for STEMI,GLS measured by CMR is a significant predictor of LVR occurrence with better performance than GRS,GCS,IS and LVEF.

Objective To evaluate the predictive value of global longitudinal strain(GLS)measured by cardiac magnetic resonance(CMR)feature-tracking technique for left ventricular remodeling(LVR)after percutaneous coronary intervention(PCI)in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A total of 403 patients undergoing PCI for acute STEMI were prospectively recruited from multiple centers in China.CMR examinations were performed one week(7±2 days)and 6 months after myocardial infarction to obtain GLS,global radial strain(GRS),global circumferential strain(GCS),ejection fraction(LVEF)and infarct size(IS).The primary endpoint was LVR,defined as an increase of left ventricle end-diastolic volume by≥20%or an increase of left ventricle end-systolic volume by≥15%from the baseline determined by CMR at 6 months.Logistic regression analysis was performed to evaluate the predictive value of CMR parameters for LVR.Results LVR occurred in 101 of the patients at 6 months after myocardial infarction.Compared with those without LVR(n=302),the patients in LVR group exhibited significantly higher GLS and GCS(P<0.001)and lower GRS and LVEF(P<0.001).Logistic regression analysis indicated that both GLS(OR=1.387,95%CI:1.223-1.573;P<0.001)and LVEF(OR=0.951,95%CI:0.914-0.990;P=0.015)were independent predictors of LVR.ROC curve analysis showed that at the optimal cutoff value of-10.6%,GLS had a sensitivity of 74.3%and a specificity of 71.9%for predicting LVR.The AUC of GLS was similar to that of LVEF for predicting LVR(P=0.146),but was significantly greater than those of other parameters such as GCS,GRS and IS(P<0.05);the AUC of LVEF did not differ significantly from those of the other parameters(P>0.05).Conclusion In patients receiving PCI for STEMI,GLS measured by CMR is a significant predictor of LVR occurrence with better performance than GRS,GCS,IS and LVEF.

Objective To investigate the mechanism of apoptosis induced by acetyl-11-keto-3-boswellic acid(AKBA)in oral squamous cell carcinoma(OSCC)cells.Methods CAL27 were randomly divided into control group(conventional culture),low-dose group(40.00 μmol·L-1 AKBA),middle-dose group(80.00 μmol·L-1 AKBA),high-dose group(120.00 μmol·L-1 AKBA),3-methyladenine(3-MA)group(120.00 μmol·L-1 AKBA+2 mmol·L-1 autophagy inhibitor 3-MA).5-ethynyl-2'-deoxyuridine(Edu)assay was used to detect cell proliferation;Western blot assay was used to detect protein expression;flow cytometry was used to detect apoptosis.Mice were randomly divided into model group(construct OSCC mouse model),AKBA-L group(10.00 mg·kg-1 AKBA after modeling),AKBA-H group(20.00 mg·kg-1 AKBA after modeling),10 animals per group.After 28 days of continuous administration,weight were detected;and the expression of related proteins were detected by Western blot assay.Results The Edu positive cell rates in control group,high-dose group were(40.18±2.53)％,(12.08±0.93)％,respectively;the protein levels of autophagy associated microtubule associated protein 1 light chain 3(LC3)Ⅱ/LC3 Ⅰ in control group,high-dose group and 3-MA group were 0.33±0.05,2.93±0.39,0.56±0.07,respectively;phosphorylated adenylate activated protein kinase catalytic subunit alpha subunit 1(p-PRKAA1)protein levels were 0.34±0.04,1.03±0.07,0.99±0.09,respectively;the apoptosis rates were(4.65±0.39)％,(25.75±2.29)％,(14.92±1.49)％,respectively.The above indexes in hige-dose group were significantly different from those in the control group(all P＜0.05).The above indexes in 3-MA group were significantly different from those in high-dose group(all P＜0.05).The tumor weight of model group,AKBA-L group and AKBA-H group were(0.96±0.08),(0.55±0.06),(0.43±0.05)g,respectively;the protein levels of LC3 Ⅱ/LC3 Ⅰ were 0.47±0.09,0.94±0.21 and 1.69±0.34,respectively.The above indexes in AKBA-L group and AKBA-H group were significantly different from those in model group(all P＜0.05).Conclusion AKBA can induce cytotoxic autophagy related apoptosis and inhibit CAL27 cell proliferation,which may be related to activation of AMPK signal.