[摘 要] 目的：探讨Shc SH2结构域结合蛋白1（SHCBP1）基因在结直肠癌（CRC）中的表达及其调控CRC细胞（Caco-2）增殖、迁移和侵袭的机制。方法：将Caco-2细胞分为4个实验组：Con组（空白对照）、sh-NC组（转染阴性对照sh-NC）、sh-SHCBP1组（转染sh-SHCBP1）、sh-SHCBP1 + 740Y-P组（转染sh-SHCBP1后用30 μmol/L PI3K激活剂740Y-P处理1 h）。采用CCK-8法、细胞划痕和Transwell实验检测细胞增殖、迁移和侵袭能力，基于Matrigel进行三维培养实验检测SHCBP1对Caco-2细胞血管生成拟态（VM）形成能力的影响，qRT-PCR检测SHCBP1的mRNA表达情况，WB法检测SHCBP1、VM相关蛋白以及PI3K/AKT/mTOR信号通路相关蛋白的表达。结果：SHCBP1在CRC组织和细胞中呈高表达（P < 0.05）。与Con组和sh-NC组相比，sh-SHCBP1组的SHCBP1的mRNA和蛋白表达水平、细胞增殖活性、划痕修复率、穿膜细胞数和形成的小管数均显著降低（均P < 0.05）；低氧诱导因子1α（HIF-1α）、Ephrin A型受体2（EPHA2）、VEGFA、p-PI3K、p-AKT和p-mTOR蛋白表达水平均显著降低（均P < 0.05）。对比sh-SHCBP1组，sh-SHCBP1 + 740Y-P组的细胞增殖活性、划痕修复率、穿膜细胞数和形成的拟态血管数均显著增加（均P < 0.05）；HIF-1α、EPHA2、VEGFA、p-PI3K、p-AKT和p-mTOR蛋白表达水平均显著增加（均P < 0.05）。结论：SHCBP1在Caco-2细胞中表达显著上调，促进Caco-2细胞的增殖、迁移和侵袭，其机制可能与激活PI3K/AKT/mTOR信号通路促进VM过程有关。

Objective To explore the clinical characteristics and related prognostic factors of hypertriglyceridemia acute pancreatitis (HTG-AP). Methods A retrospective analysis was conducted on 350 patients with HTG-AP admitted to HanZhong Central Hospital from March 2019 to March 2024. All patients received conventional treatment. They were followed up for one year after treatment. The prognosis of the patients was statistically analyzed, and logistic regression was used to analyze the related factors of prognosis. Results HTG-AP patients had an acute onset, with clinical symptoms of sudden upper abdominal pain (329/350), nausea and vomiting (275/350), acidosis (101/350), and multiple organ failure (38/350). All patients had elevated serum TG. During the follow-up period, 123 cases had a poor prognosis (poor prognosis group), and 227 cases had a good prognosis (good prognosis group). Compared with the good prognosis group, the patients in the poor prognosis group had higher levels of TG, creatinine and C-reactive protein at admission, lower levels of serum calcium and albumin, and higher proportions of diabetes mellitus history and severe conditions (P<0.05). Logistic regression analysis found that the factors related to the prognosis of patients with HTG-AP were TG level, C-reactive protein level, albumin level, history of diabetes mellitus, and moderate to severe condition (P<0.05). Conclusion HTG-AP patients have an acute onset and have main clinical symptoms of sudden upper abdominal pain, nausea and vomiting. Some patients experience systemic inflammatory reactions such as acidosis and multiple organ failure, and they may also have significantly increased serum TG. TG, C-reactive protein, albumin, history of diabetes mellitus, and severe disease conditions are associated with the prognosis of HTG-AP patients.

OBJECTIVE To formulate the Expert Consensus on the Implementation and Management of Drug Selection for Centralized Volume-Based Procurement in Medical Institutions of Guangxi （hereinafter referred to as the “ Consensus ”）， and to provide decision-making support and practical guidance for the drug selection and management of centralized volume-based procurement （hereinafter referred to as “centralized procurement”） drugs in medical institutions at all levels in Guangxi. METHODS A systematic review was conducted on the materials from previous batches of centralized procurement implemented in Guangxi. A comprehensive search was carried out for drug-related works and books， along with a systematic collation of guidelines on drug selection， expert consensus on centralized procurement， and policy documents. Through three rounds of specialized seminars， combined with existing evidence-based data and the practical drug selection experiences of medical institutions at various levels， this Consensus was formulated after thorough discussion and successive rounds of revision. RESULTS & CONCLUSIONS The Consensus systematically outlines the three key stages in the implementation of centralized procurement in medical institutions： procurement volume reporting， confirmation of agreed procurement volume， and procurement and usage implementation. It proposes drug selection strategies for centralized procurement bas ed on multiple dimensions， including specifications， dosage forms， packaging materials， fill volume， and manufacturing enterprises. In response to practical challenges encountered in the selection process， corresponding countermeasures are proposed， such as establishing a regularized information reserve mechanism， strengthening information technology support， and implementing categorized selection approaches. The Consensus advocates for medical institutions to construct an integrated “policy， data， and quality” decision-making system to promote full-cycle management of centralized procurement. This Consensus will provide scientific and practical guidance for medical institutions at all levels in Guangxi in the drug selection of centralized procurement， facilitating the smooth implementation and sustainable development of centralized procurement policies at the institutional level.

ObjectiveTo analyze the factors influencing meropenem-related liver injury （MRLI） and to explore their clinical predictive value. MethodsA retrospective case-control study was conducted， and the Chinese Hospital Pharmacovigilance System （CHPS） was used to establish a retrieval scheme. A total of 1 625 hospitalized cases using meropenem from January 2018 to December 2022 were collected. Patients were divided into case group （n=62） and control group （n=1 563） based on the presence or absence of liver injury. Clinical data and laboratory indicators from both groups were collected and analyzed. The t-test was used for comparison of normally distributed continuous data between the two groups， while the Mann-Whitney U test was used for comparison of continuous data not conforming to a normal distribution. The chi-square test was used for comparison of categorical data between the two groups. A multivariate Logistic regression analysis was performed to identify the influencing factors for MRLI. A Logistic regression equation was established， and the predictive value of these factors was assessed using the receiver operating characteristic （ROC） curve. ResultsThe results of univariate analysis indicated that the rates of male patients， hypoproteinemia， shock， intensive care unit （ICU） admissions， sepsis， and liver， gallbladder， and cardiovascular diseases， the levels of alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， aspartate aminotransferase （AST）， creatinine （CREA）， and procalcitonin （PCT）， and the number of hospitalization days were significantly higher in the case group than in the control group （P<0.05）， and that the platelet levels in the case group were significantly lower than those in the control group （P<0.05）. The multivariate Logistic regression analysis showed that male sex （odds ratio ［OR］=2.080， 95% confidence interval ［CI］： 1.050 — 4.123， P=0.036）， admission to the ICU （OR=8.207， 95%CI： 4.094‍ ‍—‍ ‍16.453， P<0.001）， comorbidity with gallbladder disease （OR=8.240， 95%CI： 3.605‍ ‍—‍ ‍18.832， P<0.001）， ALP （OR=1.012， 95%CI： 1.004‍ ‍—‍ ‍1.019， P=0.004）， GGT （OR=1.010， 95%CI： 1.005‍ ‍—‍ ‍1.015， P<0.001）， and PLT （OR=0.997， 95%CI： 0.994‍ ‍—‍ ‍0.999， P=0.020） were the influential factors for MRLI. The areas under the ROC curve of ALP， GGT， and PLT were 0.589， 0.637， and 0.595， respectively， and the AUC of them combined was 0.837. ConclusionMale sex， ICU admission， comorbidity with gallbladder disease， increased ALP， increased GGT， and decreased PLT were influencing factors for MRLI， and a combination of factors has a better predictive value for the occurrence of MRLI.

BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Ischemic stroke (IS) ranks as a leading cause of death and disability globally. The blood-brain barrier (BBB) poses significant challenges for effective drug delivery to brain tissues. Recent decades have seen the development of targeted nanomedicine and biomimetic technologies, sparking substantial interest in biomimetic drug delivery systems for treating IS. These systems are devised by utilizing or replicating natural cells and their derivatives, offering promising new pathways for detection and transport across the BBB. Their multifunctionality and high biocompatibility make them effective treatment options for IS. In addition, the incorporation of engineering techniques has provided these biomimetic drug delivery systems with active targeting capabilities, enhancing the accumulation of therapeutic agents in ischemic tissues and specific cell types. This improvement boosts drug transport and therapeutic efficacy. However, it is crucial to thoroughly understand the advantages and limitations of various engineering strategies employed in constructing biomimetic delivery systems. Selecting appropriate construction methods based on the characteristics of the disease is vital to achieving optimal treatment outcomes. This review summarizes recent advancements in three types of engineered biomimetic drug delivery systems, developed from natural cells and their derivatives, for treating IS. It also discusses their effectiveness in application and potential challenges in future clinical translation.
Humans ; Drug Delivery Systems/methods* ; Ischemic Stroke/drug therapy* ; Animals ; Blood-Brain Barrier/metabolism* ; Stroke/drug therapy*

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.