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.

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.

Infant, Newborn ; Humans ; Macrophage Activation Syndrome/diagnosis*

Objective:To investigate the risk factors of restenosis after dilation of anastomotic stenosis in patients with esophageal cancer surgery.Methods:Clinical data of 997 patients who underwent endoscopic dilation due to anastomotic stenosis after esophageal cancer radical surgery in the Affiliated Huai′an First Hospital of Nanjing Medical University from June 2015 to July 2021, were retrospectively analyzed. There were 486 cases receiving single dilation (single dilation group) and 511 cases receiving more than two dilations (multiple dilation group). The risk factors of restenosis were explored using univariate and multivariate logistic regression analysis.Results:There were 682 males and 315 females with a median age of 65 years, the median distance between the stenosis and incisor was 20 (20, 22) cm, the median stenosis diameter was 4 (3, 5) mm, and the median stenosis diameter after dilation was 11 (11, 13) mm. Univariate analysis showed that there were significant differences in the distance of the stenosis and incisor ( Z=-2.303, P<0.05), stenosis diameter ( Z=-4.637, P<0.05) and stenosis diameter after dilation ( Z=-5.773, P<0.05) between single and multiple dilation groups. Stratified multivariate logistic regression showed that for male patients, risk of multiple dilations dropped by approximately 3% for every 1-mm increase in the distance between the stenosis and incisor ( OR=0.97, 95% CI:0.93-1.00, P=0.047); the risk of multiple dilations decreased by about 15%, for every 1-mm increase in stenosis diameter ( OR=0.85, 95% CI:0.76-0.94, P=0.004); the risk of multiple dilations decreased by about 13% for every 1-mm increase in stenosis diameter after dilation ( OR=0.87, 95% CI:0.78-0.96, P=0.007). For females patients under 60 years old, the risk of multiple dilations decreased by about 31%, for every 1-mm increase in stenosis diameter after dilation ( OR=0.69, 95% CI:0.47-0.98, P=0.049); for female patients≥60 years old, the risk decreased by about 5%, for every 1-year increase in age ( OR=0.95, 95% CI:0.91-1.00, P=0.037), risk of multiple dilations dropped by 17%( OR=0.83, 95% CI:0.70-0.99, P=0.039) for every 1 mm increase in stenosis diameter after dilation. Stratified smooth curve fitting indicated that the distance between the stenosis and incisor&le;23 mm, stenosis diameter&le;4.5 mm, stenosis diameter after dilation&le;12 mm were risk factors for multiple dilations. Conclusions:The study indicates that patients with the distance between the stenosis and incisor&le;23 mm, stenosis diameter&le;4.5 mm, stenosis diameter after dilation&le;12 mm may need multiple dilations; and the first dilation should expand the stenosis diameter to 12 mm or above as far as possible to reduce the risk of restenosis in patients receiving esophageal cancer radical surgery.

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

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 investigate the correlation between heart rate index (HRI), systolic blood pressure(SBP) peak-to-SBPrest ratio (SBPR) and peak oxygen consumption (peakVO₂) in patients with chronic heart failure (CHF), and discuss the possibility of using HRI and SBPR collected during exercise to assess the exercise tolerance of CHF patients in the absence of gas analysis. Methods: In this cross-sectional study, a total of 547 patients with CHF who underwent cardiopulmonary exercise test(CPET) in Tongji Hospital Heart Rehabilitation Center Affiliated to Tongji University from March 2007 to December 2018 were collected retrospectively, focusing on their clinical data including age, gender, type of heart failure,BMI as well as data collected during their CPETs, such as peakVO₂, HRI and SBPR. Spearman univariate correlation analysis was used for statistical analysis, to unveil the correlations between peakVO₂ and those parameters, and multiple linear regression analysis was also conducted. Results: A total of 547 CHF patients conducting CPET were included in this research, of which 447 were male, at age of 63(56, 69). Univariate analysis indicates that HRI, SBPR and peakVO₂ showed significant positive correlation (r=0.323, 0.263, respectively, all P<0.001); Age and peak VO₂ showed significant negative correlation(r=-0.207, P<0.001); Male patients showed peakVO₂ higher than female(r=-0.229, P<0.001); PeakVO₂ of heart failure with reduced ejection fraction(HFrEF) was lower than heart failure with mid-range ejection fraction(HFmrEF)and heart failure with preserved ejection fraction(HFpEF) (r=0.181, P<0.001). Body mass index (BMI) had no significant correlation with peakVO₂ (P>0.05). Multivariate linear regression analysis showed that the HRI, SBPR were positively correlated with peakVO₂(t=7.68, 5.08, respectively, all P<0.05), while age and BMI showed negative correlation with peakVO₂(t=-5.43, -0.31, respectively, all P<0.05). PeakVO₂ of male was higher than female(t=-6.03, P<0.05), and peakVO₂ of HFrEF was lower than those of HFmrEF and HFpEF(t=3.17, 4.48, respectively, all P<0.05). A linear equation (F=33.52, adjusted R²=0.29) could be constructed: peakVO₂=10.65(male) or 8.53(female)+4.26HRI+3.31SBPR-0.07age-0.13BMI+0(HFrEF) or 1.05 (HFmrEF) or 1.62(HFpEF). Conclusion: HRI and SBPR are positively correlated with peakVO₂. In the absence of gas analysis, it is possible to apply HRI and SBPR during exercise to predict exercise tolerance in patients with CHF.
Chronic Disease ; Cross-Sectional Studies ; Female ; Heart Failure ; Heart Rate ; Humans ; Male ; Oxygen Consumption/physiology* ; Prognosis ; Retrospective Studies ; Stroke Volume/physiology*

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome