Metal-organic frameworks (MOFs) are crystalline materials with a multidimensional porous network structure, formed through coordination bonds with metal ions as nodes and organic ligands as connecting bridges. Due to their excellent physicochemical properties, MOFs have extensive applications in the field of biomedicine, ranging from antibacterials, drug carriers, imaging to sensors. Nanoscale metal-organic frameworks (nMOFs), commonly utilized drug carriers, can gain enhanced safety, targeted delivery, and superior therapeutic effect through endocytosis. In this review, we comprehensively summarize the factors influencing the endocytosis of nMOFs, focusing on three key physicochemical properties, particle size, morphology and surface modification. Based on different illness models, the review succinctly summarizes the latest advancements in understanding the endocytosis pathways of nMOFs while critically reflecting on the inherent limitations of current research methods. Lastly, the review offers valuable insights into future research methodologies and objectives, aiming to lay the groundwork and provide meaningful guidance for the synthesis and development of nMOFs as promising versatile drug carriers.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Objective To elucidate the clinical significance of high expression levels of endonuclease meiosis 1(EME1)in the prognosis of hepatocellular carcinoma(HCC).Methods The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were used to screen and analyze differential gene expression between HCC and non-tumor tissues.A retrospective collection of liver tissue samples from 80 HCC patients who underwent hepatectomy in the Fifth Medical Center of Chinese PLA General Hospital between January 2010 and December 2014 was performed.Immunohistochemistry analysis was employed to detect the EME1 expression levels.Survival analysis was then conducted to assess the impact of EME1 expression on 5-year postoperative survival rate of HCC patients.Additionally,gene enrichment analysis was applied to predict the function of EME1 in HCC.Results A total of 371 HCC tissue samples and 50 non-tumor liver tissue samples from TCGA database were analyzed,revealing significantly higher EME1 expression in HCC tissues.Microarray analysis of 107 samples within the GEO database(70 HCC tissues and 37 non-tumor tissues)confirmed that EME1 mRNA expression was markedly elevated in HCC tissues compared with non-tumor tissues(P<0.05).The 5-year overall survival(OS)rate was notably lower in high EME1 expression group than that in low expression group(44.1%vs.53.0%,P<0.05).Semi-quantitative immunohistochemistry analysis demonstrated that patients with high EME1 expression had a significantly lower OS rate than those with low EME1 expression(32.8%vs.45.0%,P<0.05).Multivariate COX regression analysis identified that high EME1 expression(HR=2.234,95%CI 1.073-4.649,P=0.032)and advanced China liver caner(CNLC)staging(HR=4.317,95%CI 1.799-10.359,P=0.001)were independent risk factors for the 5-year OS of post-operation patients with HCC.Conclusion Elevated EME1 expression in HCC tissues correlates with an adverse prognosis of HCC and suggests that EME1 could serve as a potential therapeutic target for HCC.

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, which poses a serious health risk to mothers and infants. In recent years, many studies have revealed the important role of exercise in preventing GDM, regulating blood glucose and ameliorating insulin resistance, as well as its potential value as an emerging therapeutic approach in improving maternal and infant outcomes and long-term health. This review discusses the latest research progress on the effect of exercise on the prevention and treatment of GDM, aims to deepen the knowledge of exercise therapy for GDM and provides guidance and assistance for the clinical treatment of GDM.
Pregnancy ; Infant ; Female ; Humans ; Diabetes, Gestational/prevention & control* ; Exercise ; Insulin Resistance ; Blood Glucose

Objective:To summarize and analyze the practice of the local practice on covering drugstore bills by pooled funds of basic medical insurance,and provide a reference for improving relevant policies.Methods:The medical insurance policies from various provinces,municipalities,autonomous regions,and coordination areas were systematically retrieved.ROST CM6 software was applied to analyze the high-frequency words and semantic network of the policy text,and combined with the interview and field investigation resultss,the key dimensions of the policy practice were identified and summarized.Then the regional differences,existing problems,and their causes were analyzed to put forward policy recommendations.Result:The selection of pharmacies covered in the payment system with outpatient expenses reimbursed by the pooled fund,the formulation of drug reimbursement list,the design of benefit plans,the management of drug prices and payments,and the supervision of hospital outflow prescriptions were five key dimensions of policy practice.There were significant differences in practice among different regions,and the problems mainly included the overall arrangement of covering pharmacies in the payment system,the mechanism of drug prices in pharmacies,and the coordination with other medical insurance policies.Conclusion:To improve the convenience of buying drugs for the insured,it is necessary to make full use of the advantages of pharmacies to meet the demand for outpatient medicine,promote the transparency of drug prices in pharmacies,coordinate the relevant medical insurance policies,strengthen the collaborative management between the healthcare security administration and relevant departments such as the health commission and the medical products administration,analyze and evaluate the potential effects of policy measures,and adjust policy measures promptly according to local conditions.

Objective To explore the effect of celecoxib on neural function in rats with acute intracerebral hemorrhage.Methods SD rats were randomly divided into sham group,model group,inhibitor group and celecoxib group.Except the sham operation group,the cerebral hemorrhage model was made by autologous blood injection in each group.Rats in the inhibitor group were injected with extra cellular regulated protein kinase(ERK)inhibitor(DCZ19931)into the anterior ventricle on the basis of the model group.Celecoxib group rats were injected intraperitoneally with 100 mg·kg 1·d-1 celecoxib,for 2 weeks.The degree of neurological injury in rats was compared by Longa five-grade score.The water content of brain tissue of rats in each group was detected and the expression of aquaporin 4(AQP4)in brain tissue of rats in each group was detected by Western blotting.Enzyme-linked immunosorbent assay was used to detect the content of interleukin-1(IL-1β),tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD)and malonaldehyde(MDA)in the brain tissue of rats in each group.Western blotting was used to detect the expression of mitogen-activated protein kinase(MAPK)/ERK signal pathway protein in rats of each group.Result Compared with sham group,the neurological function score,brain water content,relative expression level of AQP4 protein,content of IL-1β,TNF-α and MDA,relative expression levels of p-ERK1 protein,p-ERK2 protein and MAPK protein in model group were significantly increased,while content of SOD was significantly decreased(P＜0.05).Compared with model group,the neurological function score,brain water content,relative expression level of AQP4 protein,content of IL-1β,TNF-α and MDA,relative expression levels of p-ERK1 protein,p-ERK2 protein and MAPK protein in inhibitor group and celecoxib group were significantly decreased,while content of SOD was significantly increased(P＜0.05).Conclusion Celecoxib can effectively improve the neurological function of rats with acute intracerebral hemorrhage,and its mechanism may be related to the regulation of MAPK/ERK signal pathway and inhibition of inflammation.

Objective To investigate the effect of inhaled corticosteroids(ICS)on adverse outcomes in chronic obstructive pulmonary disease(COPD)(COPD-CAP)patients with community-acquired pneumonia(CAP).Methods The clinical data of COPD-CAP patients who visited the respiratory department of respiratory of Wenzhou Integrated Traditional Chinese and Western Medicine Hospital from January 2021 to January 2023 was retrosspective collected.They were divided into an ICS group and a non ICS group based on whether they were eligible for ICS treatment.A univariate analysis was used to compare the differences in general data,imaging outcomes(multilobed infiltration and pleural effusion),and clinical outcomes(non-invasive mechanical ventilation,invasive mechanical ventilation,ICU admission,and 30-day mortality)between two groups.The Logistic regression was used to explore the relationship between ICS and imaging and clinical outcomes.Result A total of 120 COPD patients were included in this study,including 38 in the ICS group,62 in the non ICS group.The univariate results showed that COPD-CAP patients in the ICS group had lower GOLD scores,PSI scores,and CURB-65 scores(P＜0.05).The multivariate Logistic regression showed that the use of ICS reduces the risk of multi leaf infiltration[OR=0.291,95％CI(0.123,0.687),P=0.005],pleural effusion[OR=0.309,95％CI(0.105,0.908),P=0.033],non-invasive mechanical ventilation[OR=0.040,95％CI(0.012,0.129),P＜0.001],invasive mechanical ventilation[OR=0.099,95％CI(0.013,0.783),P=0.028],ICU occupancy[OR=0.207,95％CI(0.056,0.762),P=0.018],and 30-day mortality[OR=0.179,95％CI(0.039,0.822),P=0.027].Conclusion ICS reduces the risk of multilobed infiltration,pleural effusion,mechanical ventilation usage,ICU occupancy,and 30-day mortality in COPD patients admitted to CAP.

Acute myeloid leukemia (AML) is a genetic heterogeneous disease in which primordial and juvenile myeloid cells proliferate or accumulate abnormally in bone marrow, peripheral blood and other tissues, resulting in damage to normal hematopoietic function. Studies have shown that about 30% of AML patients have FMS-like tyrosine kinase 3 (FLT3), FLT3 abnormal regulation is closely related to the occurrence and development of AML. At present, FLT3 has become an important target for developing small molecular targeted drugs. Currently, a variety of FLT3 inhibitors and FLT3 degraders have been developed targeting FLT3, and some compounds have exhibited good anti-AML activity. This article summarizes and sorts out the current mainstream drugs for AML therapeutic targeting FLT3, in order to provide a reference for the development and design of AML drugs.

ObjectiveTo reveal the differences of the related pathogenicity gene mutations between sebaceous adenocarcinoma （SC） of scalp and sebaceous adenoma （SA） of scalp on whole exome level. MethodsWhole exome sequencing was performed on a SC sample and a SA sample by Illumina Hiseq 2500 platform. Suspicious single nucleotide variation sites were selected for mutation conservation and functional analysis. SciClone was used to track subclone evolution and clonal map information was obtained for each tumor sample. The high-frequency significant gene mutations in the tumor sample were screened by MutSigCV software， and compared with the known driver genes. ResultsTwo driver genes TFDP1 and ACVR1B harboring mutations in scalp SC compared to SA were found. ConclusionsThe finding of mutation in driver genes TFDP1 and ACVR1B should be confirmed in a large cohort， which might reveal the mechanism of scalp SC development and find a therapeutic target for SC.

Objective: To establish a dynamic syndromic surveillance system in the border areas of Yunnan Province based on information technology, evaluate its effectiveness and timeliness in the response to common communicable disease epidemics and improve the communicable disease prevention and control in border areas. Methods: Three border counties were selected for full coverage as study areas, and dynamic surveillance for 14 symptoms and 6 syndromes were conducted in medical institutions, the daily collection of information about students' school absence in primary schools and febrile illness in inbound people at border ports were conducted in these counties from January 2016 to February 2018 to establish an early warning system based on mobile phone and computer platform for a field experimental study. Results: With syndromes of rash, influenza-like illness and the numbers of primary school absence, the most common communicable disease events, such as hand foot and mouth disease, influenza and chickenpox, can be identified 1-5 days in advance by using EARS-3C and Kulldorff time-space scanning models with high sensitivity and specificity. The system is easy to use with strong security and feasibility. All the information and the warning alerts are released in the form of interactive charts and visual maps, which can facilitate the timely response. Conclusions: This system is highly effective and easy to operate in the detection of possible outbreaks of common communicable diseases in border areas in real time, so the timely and effective intervention can be conducted to reduce the risk of local and cross-border communicable disease outbreaks. It has practical application value.
Humans ; Influenza, Human ; Sentinel Surveillance ; Syndrome ; China ; Cell Phone