Chaiqin chengqi decoction treatment mitigates hypertriglyceridemia-associated acute pancreatitis by modulating liver-mediated glycerophospholipid metabolism.

BACKGROUND: The incidence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is increasing globally and more so in China. The characteristics of liver-mediated metabolites and related key enzymes are rarely reported in HTG-AP. Chaiqin chengqi decoction (CQCQD) has been shown to protect against AP including HTG-AP in both patients and rodent models, but the underlying mechanisms in HTG-AP remain unexplored. PURPOSE: To assess the characteristics of liver-mediated metabolism and the therapeutic mechanisms of CQCQD in HTG-AP. METHODS: Male human apolipoprotein C3 transgenic (hApoC3-Tg; leading to HTG) mice or wild-type littermates received 7 intraperitoneal injections of cerulein (100 µg/kg) to establish HTG-AP and CER-AP, respectively. In HTG-AP, some mice received CQCQD (5.5 g/kg) gavage at 1, 5 or 9 h after disease induction. AP severity and related liver injury were determined by serological and histological parameters; and underlying mechanisms were identified by lipidomics and molecular biology. Molecular docking was used to identify key interactions between CQCQD compounds and metabolic enzymes, and subsequently validated in vitro in hepatocytes. RESULTS: HTG-AP was associated with increased disease severity indices including augmented liver injury compared to CER-AP. CQCQD treatment reduced severity and liver injury of HTG-AP. Glycerophospholipid (GPL) metabolism was the most disturbed pathway in HTG-AP in comparison to HTG alone. In HTG-AP, the mRNA level of GPL enzymes involved in phosphocholine (PC) and phosphatidylethanolamine (PE) synthesis (Pcyt1a, Pcyt2, Pemt, and Lpcat) were markedly upregulated in the liver. Of the GPL metabolites, lysophosphatidylethanolamine LPE(16:0) in serum of HTG-AP was significantly elevated and positively correlated with the pancreas histopathology score (r = 0.65). In vitro, supernatant from Pcyt2-overexpressing hepatocytes co-incubated with LPE(16:0) or phospholipase A2 (a PC- and PE-hydrolyzing enzyme) alone induced pancreatic acinar cell death. CQCQD treatment downregulated PCYT1a and PCYT2 enzyme levels in the liver. Hesperidin and narirutin were identified top two CQCQD compounds with highest affinity docking to PCYT1a and PCYT2. Both hesperidin and narirutin reduced the level of some GPL metabolites in hepatocytes. CONCLUSION: Liver-mediated GPL metabolism is excessively activated in HTG-AP with serum LPE(16:0) level correlating with disease severity. CQCQD reduces HTG-AP severity partially via modulating key enzymes in GPL metabolism pathway.

Inner Side Chain Modification of Small Molecule Acceptors Enables Lower Energy Loss and High Efficiency of Organic Solar Cells Processed with Non-halogenated Solvents.

Organic solar cells (OSCs) processed with non-halogenated solvents usually suffer from excessive self-aggregation of small molecule acceptors (SMAs), severe phase separation and higher energy loss (Eloss), leading to reduced open-circuit voltage (Voc) and power conversion efficiency (PCE). Here, we designed and synthesized two SMAs L8-PhF and L8-PhMe by introducing different substituents (fluorine for L8-PhF and methyl for L8-PhMe) on the phenyl end group of inner side chains of L8-Ph, and investigated the effect of the substituents on the intermolecular interaction of SMAs, Eloss and performance of OSCs processed with non-halogenated solvents. It is found that compared with L8-PhF, which possesses strong intermolecular interactions but downgraded molecular packing order, L8-PhMe exhibits more effective non-covalent interactions, which improves the tightness and order of molecular packing. When blending the SMAs with PM6, the OSCs based on L8-PhMe shows reduced non-radiative energy loss, and enhanced Voc than the devices based on the other two SMAs. Consequently, the L8-PhMe based device processed with o-xylene and using 2PACz as the hole transport layer shows an outstanding PCE of 19.27%. This study highlights that the Eloss of OSCs processed with non-halogenated solvents could be decreased through regulating the intermolecular interactions of SMAs by inner side chain modification.

Combinations of immunomodulatory agents for prevention of uveitis relapse in patients with severe Behçet's disease already on corticosteroid therapy: a randomised, open-label, head-to-head trial.

BACKGROUND: Data from head-to-head trials of immunomodulatory therapies for Behçet's disease are scarce. We aimed to compare the efficacy and safety of ciclosporin, interferon alfa-2a, and adalimumab, each combined with corticosteroids, in preventing uveitis relapse in patients with severe Behçet's disease. METHODS: We did a randomised, open-label, assessor-masked, head-to-head trial at a large, specialised uveitis centre in Chongqing, China. Patients aged 18 years or older with severe Behçet's disease uveitis on corticosteroids and naive to anti-TNF therapy were eligible. Patients were randomly assigned in a 1:1:1 ratio to ciclosporin (2-5 mg/kg per day orally), interferon alfa-2a (3 million IU per day subcutaneously), or adalimumab (40 mg every 2 weeks subcutaneously), each combined with a tapering dose of corticosteroids with subsequent dose adjustments. The primary outcome was the annualised relapse rate of uveitis, assessed in the full analysis set (all randomly assigned patients with at least one post-baseline assessment). The non-inferiority margin of difference between the interferon alfa-2a and adalimumab groups was set to 1·0 for the primary outcome. Safety was assessed in all patients who received at least one dose of trial drugs. Individuals with lived experience of Behçet's disease uveitis were involved in the trial design and implementation. This study is registered with Chinese Clinical Trial Registry, ChiCTR2000031637. The trial is ongoing, but is closed to new participants. FINDINGS: Between May 12, 2020, and Feb 22, 2022, a total of 270 patients (mean age 38·1 years [SD 9·8]; 213 [79%] men, 57 [21%] women; 270 [100%] east Asian ethnicity) were randomly assigned to ciclosporin, interferon alfa-2a, or adalimumab (n=90 in each group); 261 patients were included in the full analysis set. For the primary outcome, the least-squares mean was 1·84 (95% CI 1·40 to 2·44) with ciclosporin, 1·44 (1·10 to 1·89) with interferon alfa-2a, and 0·95 (0·64 to 1·40) with adalimumab. The annualised relapse rate was significantly higher in patients receiving ciclosporin than in those receiving adalimumab (least-squares mean difference 0·90 [95% CI 0·27 to 1·53]; p=0·0054 for superiority). The least-squares mean difference between interferon alfa-2a and adalimumab was 0·50 (-0·04 to 1·04), which did not meet non-inferiority criteria (p=0·034 for non-inferiority). The primary outcome did not differ substantially between interferon alfa-2a and ciclosporin (least-squares mean difference -0·40 [-1·05 to 0·25]; p=0·23 for superiority). Serious adverse events were reported in 12 (13%) of 90 patients on ciclosporin plus corticosteroids, eight (9%) of 90 patients on interferon alfa-2a plus corticosteroids, and seven (8%) of 90 patients on adalimumab plus corticosteroids. There were no treatment-related deaths. INTERPRETATION: Adalimumab plus corticosteroids was superior to ciclosporin plus corticosteroids with respect to uveitis relapse rate in patients with severe Behçet's disease naive to anti-TNF therapy, and interferon alfa-2a plus corticosteroids was not found to be non-inferior to adalimumab plus corticosteroids or superior to ciclosporin plus corticosteroids. FUNDING: National Natural Science Foundation of China Key Program, Major Program of Medical Science and Technology Project of Health Commission of Henan Province, Chongqing Key Laboratory of Ophthalmology, and China National Postdoctoral Program for Innovative Talents.

Effects of ultrasonic waves of different powers on the physicochemical properties, functional characteristics, and ultrastructure of bovine liver peptides.

In recent years, ultrasound has emerged as a widely used technology for modifying proteins/peptides. In this study, we focused on the intrinsic mechanism of ultrasound-induced modification of bovine liver peptides, which were treated with ultrasound power of 0, 100, 200, 300, 400, and 500 W, and their physicochemical and functional properties, as well as ultrastructures, were investigated. The results show that ultrasound mainly affects hydrogen bonding and hydrophobic interactions to change the conformation of proteins and unfolds proteins through a cavitation effect, leading to an increase in biological activity. Fourier infrared spectroscopy showed that ultrasound inhibited the formation of hydrogen bonds and reduced intermolecular cross-linking. Molecular weight distribution showed that the antioxidant components of bovine liver polypeptides were mainly concentrated in fractions of 500-1,000 Da. Maximum values of ABTS (82.66 %), DPPH (76.02 %), chelated iron (62.18 %), and reducing power (1.2447) were obtained by treating bovine liver polypeptides with 500 W ultrasound. Combined with the scanning electron microscopy results, with the intervention of ultrasound, the impact force generated by ultrasonication may lead to the loosening of the protein structure, which further promotes the release of antioxidant peptides, and these findings provide new insights into the application of ultrasound in the release of antioxidant peptides from bovine liver.

A molybdenum sulfide based nitric oxide controlled release oral gel for rapid healing of oral mucosal ulcers.

Oral mucosal ulcer is the most prevalent oral mucosal lesion, affecting over 25 % of general population. The current treatment regimens lack efficacy in addressing challenges such as wound bleeding, bacterial infection and inflammation on a continuous basis. Hence, a multi-functional oral gel (termed MPCST) with a long-acting duration is designed. It is based on a tannic acid-thioctic acid (TATA) supramolecular hydrogel which absorbs tissue exudate while exhibiting robust tissue adhesion properties. To form MPCST, TATA is loaded with MPCS, which are composed of polydopamine (PDA)-coated molybdenum disulfide (MoS2) nanoflakes (MoS2@PDA) with high photothermal conversion efficiency, nitric oxide (NO) precursor nitroprusside (SNP) and cerium oxide (CeO2) with high reactive oxygen species (ROS) scavenging rate. Upon exposure to 808 nm near-infrared (NIR) irradiation, MPCS rapidly heats up and releases NO to promote angiogenesis, while exhibiting strong ROS scavenging, antibacterial (including oral common Streptococcus mutans), and anti-inflammatory properties. Animal experiments show that the MPCST oral gel, composed of MPCS and TATA hydrogel, exhibits superior therapeutic efficacy compared to the commonly used dexamethasone patch.

Prognostic value of angiographic microvascular resistance in patients with ST-segment elevation myocardial infarction.

BACKGROUND: The Angiographic Microvascular Resistance (AMR), derived from a solitary angiographic view, has emerged as a viable substitute for the Index of Microcirculatory Resistance (IMR). However, the prognostic significance in ST-Segment Elevation Myocardial Infarction (STEMI) patients is yet to be established. This research endeavors to explore the prognostic capabilities of AMR in patients diagnosed with STEMI. METHODS: In this single-center, retrospective study, 232 patients diagnosed with STEMI who received primary Percutaneous Coronary Intervention (PCI) were recruited from January 1, 2018, to June 30, 2022. Utilizing the maximally selected log-rank statistics analysis, participants were divided into two cohorts according to an AMR threshold of 2.55 mmHg*s/cm. The endpoint evaluated was a composite of all-cause mortality or hospital readmission due to heart failure. RESULTS: At a median follow-up of 1.74 (1.07, 3.65) years, the composite endpoint event was observed in 28 patients within the higher AMR group and 8 patients within the lower AMR group. The higher AMR group showed a significantly higher risk for composite outcome compared to those within the low-AMR group (HRadj: 3.33; 95% CI 1.30‒8.52; p = 0.03). AMR ≥ 2.55 mmHg*s/cm was an independent predictor of the composite endpoint (HR = 2.33; 95% CI 1.04‒5.21; p = 0.04). Furthermore, a nomogram containing age, sex, left ventricle ejection fraction, post-PCI Quantitative Flow Ratio (QFR), and AMR was developed and indicated a poorer prognosis in the high-risk group for STEMI patients at 3 years. (HR=4.60; 95% CI 1.91‒11.07; p < 0.01). CONCLUSIONS: AMR measured after PCI can predict the risk of all-cause death or readmission for heart failure in patients with STEMI. AMR-involved nomograms improved predictive performance over variables alone.

Multifunctional hydrogels based on photothermal therapy: A prospective platform for the postoperative management of melanoma.

Preventing the recurrence of melanoma after surgery and accelerating wound healing are among the most challenging aspects of melanoma management. Photothermal therapy has been widely used to treat tumors and bacterial infections and promote wound healing. Owing to its efficacy and specificity, it may be used for postoperative management of tumors. However, its use is limited by the uncontrollable distribution of photosensitizers and the likelihood of damage to the surrounding normal tissue. Hydrogels provide a moist environment with strong biocompatibility and adhesion for wound healing owing to their highly hydrophilic three-dimensional network structure. In addition, these materials serve as excellent drug carriers for tumor treatment and wound healing. It is possible to combine the advantages of both of these agents through different loading modalities to provide a powerful platform for the prevention of tumor recurrence and wound healing. This review summarizes the design strategies, research progress and mechanism of action of hydrogels used in photothermal therapy and discusses their role in preventing tumor recurrence and accelerating wound healing. These findings provide valuable insights into the postoperative management of melanoma and may guide the development of promising multifunctional hydrogels for photothermal therapy.

Sources and applications of endothelial seed cells: a review.

Endothelial cells (ECs) are widely used as donor cells in tissue engineering, organoid vascularization, and in vitro microvascular model development. ECs are invaluable tools for disease modeling and drug screening in fundamental research. When treating ischemic diseases, EC engraftment facilitates the restoration of damaged blood vessels, enhancing therapeutic outcomes. This article presents a comprehensive overview of the current sources of ECs, which encompass stem/progenitor cells, primary ECs, cell lineage conversion, and ECs derived from other cellular sources, provides insights into their characteristics, potential applications, discusses challenges, and explores strategies to mitigate these issues. The primary aim is to serve as a reference for selecting suitable EC sources for preclinical research and promote the translation of basic research into clinical applications.

Aging-induced short-chain acyl-CoA dehydrogenase promotes age-related hepatic steatosis by suppressing lipophagy.

Hepatic steatosis, the first step in the development of nonalcoholic fatty liver disease (NAFLD), is frequently observed in the aging population. However, the underlying molecular mechanism remains largely unknown. In this study, we first employed GSEA enrichment analysis to identify short-chain acyl-CoA dehydrogenase (SCAD), which participates in the mitochondrial ß-oxidation of fatty acids and may be associated with hepatic steatosis in elderly individuals. Subsequently, we examined SCAD expression and hepatic triglyceride content in various aged humans and mice and found that triglycerides were markedly increased and that SCAD was upregulated in aged livers. Our further evidence in SCAD-ablated mice suggested that SCAD deletion was able to slow liver aging and ameliorate aging-associated fatty liver. Examination of the molecular pathways by which the deletion of SCAD attenuates steatosis revealed that the autophagic degradation of lipid droplets, which was not detected in elderly wild-type mice, was maintained in SCAD-deficient old mice. This was due to the decrease in the production of acetyl-coenzyme A (acetyl-CoA), which is abundant in the livers of old wild-type mice. In conclusion, our findings demonstrate that the suppression of SCAD may prevent age-associated hepatic steatosis by promoting lipophagy and that SCAD could be a promising therapeutic target for liver aging and associated steatosis.

Hydrogel-Based Treatment of House Dust Mite-Induced Atopic Dermatitis through Triple Cleaning of Mites, Bacteria, and ROS-Related Inflammation.

Atopic dermatitis (AD) is a chronic and recurrent inflammatory disease caused by abnormalities in skin immunoregulation. House dust mite can directly damage the skin barrier and thus sensitize the skin, which is one of the main allergens inducing AD in humans and widely exists in daily life. Meanwhile, the accompanying bacterial infections and exposure to additional allergens exacerbate the condition by generating excessive reactive oxygen species (ROS). Herein, we have developed the CPDP hydrogel with injectable and self-healing ability to combat pathogenic microorganisms and inflammatory environments for AD therapy. In vitro experiments have affirmed the efficacy of the CPDP hydrogel in combating mites, killing bacteria, and scavenging ROS. In a mouse model closely mimicking HDM-induced AD, the CPDP hydrogel has shown superior therapeutic effects, including reducing epidermal thickness and mast cell count, increasing collagen deposition, as well as down-regulating pro-inflammatory factors.

Exploring hot topics and evolutionary paths in the Diagnosis-Related Groups (DRGs) field: a comparative study using LDA modeling.

BACKGROUND: This study reviews the research status of Diagnosis-related groups (DRGs) payment system in China and globally by analyzing topical issues in this field and exploring the evolutionary trends of DRGs in different developmental stages. METHODS: Abstracts of relevant literature in the field of DRGs were extracted from the China National Knowledge Infrastructure (CNKI) database and the Web of Science (WoS) core database and used as text data. A probabilistic distribution-based Latent Dirichlet Allocation (LDA) topic model was applied to mine the text topics. Topical issues were determined by topic intensity, and the cosine similarity of the topics in adjacent stages was calculated to analyze the topic evolution trend. RESULTS: A total of 6,758 English articles and 3,321 Chinese articles were included. Foreign research on DRGs focuses on grouping optimization, implementation effects, and influencing factors, whereas research topics in China focus on grouping and payment mechanism establishment, medical cost change evaluation, medical quality control, and performance management reform exploration. CONCLUSIONS: Currently, the field of DRGs in China is developing rapidly and attracting deepening research. However, the implementation depth of research in China remains insufficient compared with the in-depth research conducted abroad.

Non-Invasive Assessment of Coronary Microvascular Dysfunction Using Vascular Deformation-Based Flow Estimation.

OBJECTIVE: Non-invasive computation of the index of microcirculatory resistance from coronary computed tomography angiography (CTA), referred to as IMR[Formula: see text], is a promising approach for quantitative assessment of coronary microvascular dysfunction (CMD). However, the computation of IMR[Formula: see text] remains an important unresolved problem due to its high requirement for the accuracy of coronary blood flow. Existing CTA-based methods for estimating coronary blood flow rely on physiological assumption models to indirectly identify, which leads to inadequate personalization of total and vessel-specific flow. METHODS: To overcome this challenge, we propose a vascular deformation-based flow estimation (VDFE) model to directly estimate coronary blood flow for reliable IMR[Formula: see text] computation. Specifically, we extract the vascular deformation of each vascular segment from multi-phase CTA. The concept of inverse problem solving is applied to implicitly derive coronary blood flow based on the physical constraint relationship between blood flow and vascular deformation. The vascular deformation constraints imposed on each segment within the vascular structure ensure sufficient individualization of coronary blood flow. RESULTS: Experimental studies on 106 vessels collected from 89 subjects demonstrate the validity of our VDFE, achieving an IMR[Formula: see text] accuracy of 82.08 %. The coronary blood flow estimated by VDFE has better reliability than the other four existing methods. CONCLUSION: Our proposed VDFE is an effective approach to non-invasively compute IMR[Formula: see text] with excellent diagnostic performance. SIGNIFICANCE: The VDFE has the potential to serve as a safe, effective, and cost-effective clinical tool for guiding CMD clinical treatment and assessing prognosis.

Review: Progress towards research on the toxicology of pyrimethanil.

Pyrimethanil is a persistent environmental pollutant that poses a significant threat to human health. In this review, we summarize the fungicidal mechanism of pyrimethanil and its toxicological effects on aquatic organisms and mammals, as well as its impact on growth and development as an endocrine disruptor. Additionally, we investigate the metabolism of pyrimethanil in mammals and its molecular mechanism in the occurrence of Alzheimer's disease. Furthermore, this review outlines the influence of climate change on the toxicity of pyrimethanil, emphasizing the need to consider the impact of mixtures of multiple compounds on human health. Finally, we propose several promising future directions for pyrimethanil research, believing that there is a better understanding of the interaction between pyrimethanil and organisms, as well as the development of techniques to remove pyrimethanil, may be the best approach to eliminating the threat posed by this compound.

Associations between benign paroxysmal positional vertigo and seven mental disorders: a two-sample Mendelian randomization study.

Background: The association between benign paroxysmal positional vertigo (BPPV) and various mental disorders is still controversial. This study used the Mendelian randomization (MR) method to clarify the correlation between BPPV and seven mental disorders (bipolar disorder, depression, anxiety disorder, schizophrenia, suicidality, neuroticism, and mood swings) to aid in the exploration of BPPV complications and prevention and early treatment of mental disorders. Methods: The datasets for BPPV and seven mental disorders were obtained from genome-wide association studies (GWASs). Two-sample MR was used to analyze the correlation between exposure (BPPV) and various outcomes (bipolar disorder, depression, anxiety disorder, schizophrenia, suicidality, neuroticism, and mood swings). A reverse MR study was also performed. The inverse variance weighting (IVW) method, the MR-Egger method, the simple mode method, the weighted mode method, and the weighted median method were selected. Results: The MR analysis and the reverse MR analysis results did not reveal significant associations between BPPV and bipolar disorder, depression, anxiety disorder, schizophrenia, suicidal tendencies, neuroticism, and mood swings. Interestingly, neuroticism (IVW: OR = 1.142, 95% CI: 1.059-1.231, P = 0.001; P-MR-PRESSO adjustment = 0.0002) and mood swings (IVW: OR = 3.119, 95% CI: 1.652-5.884, P = 0.0004) may have a significant association with BPPV. After MR-PRESSO adjustment, there was no horizontal pleiotropy or heterogeneity, and a significant association between neuroticism, mood swings, and BPPV has still been suggested. Conclusion: We conducted MR analysis on genetic data from European populations and discovered a causal relationship between BPPV and the seven mental disorders. Our research findings suggest that BPPV may not have a significant causal relationship with bipolar disorder, depression, anxiety disorder, schizophrenia, or suicidal tendencies. However, neuroticism and mood swings may be risk factors for BPPV.

Promoter hypomethylated PDZK1 acts as a tumorigenic gene in glioma by interacting with AKT1.

Glioma is the most frequently diagnosed primary brain tumor and typically has a poor prognosis because of malignant proliferation and invasion. It is urgent to elucidate the mechanisms driving glioma tumorigenesis and develop novel treatments to address this deadly disease. Here, we first revealed that PDZK1 is expressed at high levels in gliomas. Promoter hypomethylation may cause high expression of PDZK1 in glioma. Knockdown of PDZK1 inhibits glioma cell proliferation and invasion in vitro. Mechanistically, further investigations revealed that the loss of PDZK1 expression by siRNA inhibited the activation of the AKT/mTOR signaling pathway, leading to cell cycle arrest and apoptosis. Clinically, high expression of PDZK1 predicts a poorer prognosis for glioma patients than low expression of PDZK1. Overall, our study revealed that PDZK1 acts as a novel oncogene in glioma by binding to AKT1 and maintaining the activation of the AKT/mTOR signaling pathway. Thus, PDZK1 may be a potential therapeutic target for glioma.

Clinical and Dermoscopic Insights Into Scalp Nevi in Chinese Children.

BACKGROUND: The presence of scalp nevi in children frequently causes apprehension, leading physicians and parents to consider unnecessary biopsies or excisions of scalp nevi in children. There are limited data on the dermoscopic characteristics of scalp nevi in Chinese children. OBJECTIVE: The aim of this study was to comprehensively analyze the clinical and dermoscopic features of scalp nevi in this specific population of Chinese pediatric patients, with a focus on a single pediatric dermatologic surgery practice. METHODS: This retrospective cohort study investigated patients who underwent surgical excision of scalp nevi. All patients underwent dermoscopy with photographic documentation. RESULTS: Seventy-two scalp nevi in 56 Chinese children were included. Notably, no melanoma cases were detected. The parietal region (35, 48.6%) was the most frequently affected anatomical site. Clinical asymmetry was more prevalent in nevi with a diameter exceeding 6 mm ( p < .05). The predominant dermoscopic pattern observed was the globular pattern (50, 69.4%) while an intriguing rarity of a reverse-eclipse pattern (1, 1.4%). CONCLUSION: This study revealed that scalp nevi in Chinese children usually did not exhibit concerning behavior. Increasing awareness of the clinical characteristics, dermoscopic features, and the natural progression of scalp nevi in children can potentially help reduce unnecessary surgical interventions.

[Relationship Between Tim-3 and Galectin-9 Expression Levels, Clinical Pathological Characteristics, and Prognosis in Patients After Radical Resection of Colorectal Cancer]. / ç»“ç›´è‚ ç™Œæ ¹æ²»æœ¯åŽæ‚£è€ Tim-3、galectin-9è¡¨è¾¾æ°´å¹³ä¸Žå ¶ä¸´åºŠç— ç†ç‰¹å¾åŠé¢„åŽçš„å ³ç³».

Objective: Some colorectal cancer patients still face high recurrence rates and poor prognoses even after they have undergone the surgical treatment of radical resection. Identifying potential biochemical markers and therapeutic targets for the prognostic evaluation of patients undergoing radical resection of colorectal cancer is crucial for improving their clinical outcomes. Recently, it has been reported that the T cell immunoglobulin and mucin domain protein 3 (Tim-3) and its ligand galactose lectin 9 (galectin-9) play crucial roles in immune dysfunction caused by various tumors, such as colorectal cancer. However, their expressions, biological functions, and prognostic value in colorectal cancer are still unclear. This study aims to investigate the relationship between Tim-3 and galectin-9 expression levels and the clinicopathological characteristics and prognosis of patients undergoing radical resection of colorectal cancer. Methods: A total of 171 patients who underwent radical resection of colorectal cancer at Chengdu Fifth People's Hospital between February 2018 and March 2019 were selected. Immunohistochemistry was performed to assess the expression levels of Tim-3 and galectin-9 in the cancer tissue samples and the paracancerous tissue samples of the patients. The relationship between Tim-3 and galectin-9 expression levels and the baseline clinical parameters of the patients was analyzed accordingly. Kaplan-Meier analysis was performed to assess the association between Tim-3 and galectin-9 expression levels and the relapse-free survival (RFS) and the overall survival (OS) of colorectal cancer patients. Cox regression analysis was conducted to identify factors associated with adverse prognosis in the patients. Results: The immunohistochemical results showed that the high expression levels of Tim-3 and galectin-9 were observed in 70.18% (120/171) and 32.16% (55/171), respectively, of the colorectal cancer tissues, whereas the low expression levels were 29.82% (51/171) and 67.84% (116/171), respectively. Furthermore, the expression score of Tim-3 was significantly higher in colorectal cancer tissues than that in the paracancerous tissues, while the expression score of galectin-9 was lower than that in the paracancerous tissues (P<0.05). Further analysis revealed that the expression of Tim-3 and galectin-9 was associated with the depth of tumor infiltration, vascular infiltration, and clinical staging (P<0.05). During the follow-up period of 14-63 months, 7 out of 171 patients were lost to follow-up. Among the remaining patients, 49 and 112 cases presented abnormally low expression of Tim-3 and galectin-9, respectively, whereas 115 and 52 cases presented high expression of Tim-3 and galectin-9, respectively. Kaplan-Meier survival analysis demonstrated that patients with high Tim-3 expression in colorectal cancer tissues had significantly lower RFS and OS than those with low expression did (RFS: log-rank=22.66, P<0.001; OS: log-rank=19.71, P<0.001). Conversely, patients with low galectin-9 expression had significantly lower RFS and OS than those with high expression did (RFS: log-rank=19.45, P<0.001; OS: log-rank=22.24, P<0.001). Cox multivariate analysis indicated that TNM stage Ⅲ (HR=2.26, 95% CI: 1.20-5.68), high expression of Tim-3 (HR=0.80, 95% CI: 0.33-0.91), and low expression of galectin-9 (HR=1.80, 95% CI: 1.33-4.70) were independent risk factors affecting RFS and OS in patients (P<0.05). Conclusion: Aberrant expression of Tim-3 and galectin-9 is observed in colorectal cancer tissues. High expression of Tim-3 and low expression of galectin-9 are closely associated with adverse clinico-pathological characteristics and prognosis. They are identified as independent influencing factors that may trigger adverse prognostic events in patients. These findings suggest that Tim-3 and galectin-9 have potential as new therapeutic targets and clinical indicators.

Evaluation and associated factors of public health emergency management among medical college students in a city in Southwest China: a cross-sectional study.

BACKGROUND: Colleges and universities face an increased risk of public health emergencies. Among them, medical colleges and universities deserve more attention as they serve as the play a fundamental role in providing public health emergency services and in cultivating medical professionals. Effectively managing infectious disease prevention and control, as well as responding to public health emergencies in medical colleges and universities, is of great importance for enhancing the capacity of social emergency governance and improving the completeness of the public health system. This study aims to understand the management of public health emergencies in medical colleges in a city in southwest China, explore the factors associated with medical college students' evaluations, and provide recommendations for emergency management mechanisms in colleges and universities. METHODS: In total, 781 medical college students were selected through stratified random sampling and surveyed using a questionnaire. The main factors affecting students' evaluation of emergency management were analyzed using multiple linear regression and structural equation modeling. RESULTS: The overall emergency management situation in medical colleges was relatively complete, with satisfactory results. Medical college students' satisfaction with the timeliness of prevention measures was the highest, while the publicity and education were the lowest. Multiple linear regression analysis showed that grades, emergency education, -simulation training, -information reporting, and dynamic adjustment measures were associated with the evaluation of emergency management by medical students. CONCLUSIONS: Although the evaluation of emergency management in medical colleges was generally positive, certain limitations still existed. To improve the development of the public health system, colleges and universities should constantly reform and innovate emergency management mechanisms according to the important links in the prevention and control processes.