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Duodenal-type follicular lymphoma (DFL) is a unique subtype of follicular lymphoma (FL), which often involves the second portion of duodenum (descending part of duodenum). Due to its specific pathological features, such as lack of follicular dendritic cells meshwork and disappearance of activation-induced cytidine deaminase expression, DFL presents an inert clinical course and is often confined to the intestinal tract. Inflammation-related biomarkers suggest that the microenvironment may play a likely role in the pathogenesis and favorable prognosis of DFL. Since patients generally have no obvious clinical symptoms and low progression rate, the treatment regimen for DFL is mainly observation and waiting (W&W) strategy. This study will review the latest research progress of epidemiology, diagnosis, treatment and prognosis of DFL in recent years.
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Humans , Lymphoma, Follicular/drug therapy , Duodenal Neoplasms/pathology , Prognosis , Tumor MicroenvironmentABSTRACT
OBJECTIVE@#To investigate the therapeutic effect of gentisic acid (GA) on rheumatoid arthritis (RA) based on the miR-19b-3p/RAF1 axis.@*METHODS@#The cell counting kit-8 method was used to detect the growth inhibitory effect of different concentrations of GA on MH7A cells, and the drug concentration of GA was determined in the experiment. The quantificational real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-19b-3p and RAF1. RAF1, extracellular regulated protein kinases1/2 (ERK1/2) and phospho-ERK1/2 (p-ERK1/2) were examined by Western blotting. Three methods (dual-luciferase assay, qRT-PCR and Western blot analysis) were used to verify miR-19b-3p targeting RAF1. Flow cytometry was performed to detect MH7A cell apoptosis. Transwell and wound healing assays were used to determine the invasion and migration capacities of MH7A cells.@*RESULTS@#The growth of MH7A cells was gradually inhibited with increasing GA concentration. When the GA concentration exceeded 80 mmol/L, GA was significantly cytotoxic to MH7A cells, so the half maximal inhibitory concentration of GA for MH7A cells was calculated as 67.019 mmol/L. GA upregulated miR-19b-3p expression, downregulated RAF1 expression, inhibited ERK1/2 phosphorylation, induced MH7A cell apoptosis and suppressed MH7A cell invasion and migration (P<0.05 or P<0.01). RAF1 was identified as the target of miR-19b-3p and reversed inhibitory effects on miR-19b-3p expression (P<0.05 or P<0.01). The miR-19b-3p inhibitor upregulated RAF1 expression and ERK1/2 phosphorylation, suppressed MH7A cell apoptosis and induced MH7A cell invasion and migration (P<0.01).@*CONCLUSION@#GA regulated miR-19b-3p/RAF1 axis to mediate ERK pathway and inhibit the development of RA.
Subject(s)
Humans , Cell Proliferation , MicroRNAs/metabolism , Arthritis, Rheumatoid/genetics , Gentisates/pharmacology , Cell Movement/geneticsABSTRACT
Objective:A high performance liquid chromatography (HPLC) method was developed to determine the enzymatic activity of CD38 in blood, which was the major enzyme responsible for consuming nicotinamide adenine dinucleotide (NAD). Additionally, the study aimed to detect the differences in CD38 enzymatic activity among individuals of varying ages and health statuses.Methods:A 50 μl whole blood matrix and enzyme reaction substrate of 150 μl β-NAD at a concentration of 500 μmol/L were selected for the analysis. To eliminate the impact of endogenous β-NAD, the whole blood sample was pre-incubated at 37 ℃ for 20 minutes before adding the substrate. The reaction was terminated by perchloric acid (PCA) after incubation at 37 ℃ for 40 min. The change in product nicotinamide (NAM) before and after the enzymatic reaction was measured by HPLC to calculate the CD38 activity. The linearity, limit of detection, limit of quantification, precision, and stability of the method were evaluated. The CD38 enzymatic activities in 60 healthy volunteers and 30 colorectal cancer patients in blood were determined by the developed method.Results:Pre-incubation at 37 ℃ for 20 minutes eliminated the effect of endogenous β-NAD. The correlation coefficient of NAM was 0.999 in the concentration range of 0.1-3.2 μmol/L, with limit of detection of 0.5 nmol/L and limit of quantification of 2.1 nmol/L. The average within-run imprecision ( CV) and total CV were 3.22%-4.03% and 2.91%-4.70%, respectively. The recovery rate ranged from 94.82% to 96.81%. The CD38 activity of whole blood was stable by storage at 4 ℃ for 48 hours, storage at room temperature for 8 hours, thawing of frozen whole blood at room temperature for 2 hours, or repeated freeze-thawing three times. NAM, NAD standards, and pre-treatment samples were stable after 48 hours at 4 ℃ and 8 hours at room temperature. CD38 activity gradually decreased with increasing concentration of the added CD38 inhibitor 4-aminoquinoline derivative (78c). Measurement of 60 healthy physical examination population samples showed significantly higher CD38 enzyme activity in the elderly group than that in the young group ( t=-2.776, P=0.007) and measurement of 30 colorectal cancer patients showed significantly higher CD38 enzyme activity than that in healthy people ( t=-2.572, P=0.012). Conclusion:The established HPLC method for determining CD38 enzymatic activity is characterized by its simplicity, efficiency, accuracy, and reproducibility. This technique serves as a valuable tool for investigating aging and aging-related diseases.
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OBJECTIVE@#To establish a visual reporting system for evaluating the activity of collagen Ⅰ α 1 chain (COL1A1) gene promoter in immortalized human hepatic stellate cells, so as to estimate the activation status of the cells and provide a new cell model for the screening and study of anti-hepatic fibrosis drugs.@*METHODS@#The promoter sequence of human COL1A1 was amplified from the genomic DNA of human hepatocarcinoma cell line HepG2. Based on the pLVX-AcGFP1-N1 plasmid, the recombinant plasmid pLVX-COL1A1-enhanced green fluorescent protein (EGFP) was constructed, in which the enhanced green fluorescent protein gene expression was regulated by the COL1A1 promoter. The monoclonal cell line was acquired by stably transfecting pLVX-COL1A1-EGFP into the immortalized human hepatic stellate cell line LX-2 by the lentivirus packaging system and screening. The cell line was treated with transforming growth factor-β1 (TGF-β1) or co-treated with TGF-β1 and drugs with potential anti-hepatic fibrosis effects. The EGFP fluorescence intensity in cells was analyzed by the fluorescence microscope and ImageJ 1.49 software using a semi-quantitative method. The COL1A1 and EGFP mRNA were detected by reverse transcription real-time quantitative PCR (RT-qPCR), and corresponding proteins were detected by Western blot.@*RESULTS@#The recombinant plasmid pLVX-COL1A1-EGFP with the expression of EGFP regulated by COL1A1 promoter was successfully constructed. Kozak sequence was added to enhance the expression of EGFP, which was identified by double digestion and sequencing. The LX-2 monoclonal cell line LX-2-CE stably transfected with pLVX-COL1A1-EGFP was obtained. After co-treatment with TGF-β1 and 5 μmol/L dihydrotanshinone Ⅰ with potential anti-hepatic fibrosis effect for 24 h, the total fluorescence intensity and the average fluorescence intensity of LX-2-CE were lower than those in TGF-β1 single treatment group (P < 0.05), the intracellular mRNA and protein levels of COL1A1 and EGFP were also lower than those in the TGF-β1 single treatment group (P < 0.05).@*CONCLUSION@#A reporter system for estimating activation of hepatic stellate cells based on COL1A1 promoter regulated EGFP expression is successfully constructed, which could visually report the changes in COL1A1 expression, one of the activation-related markers of hepatic stellate cells, in vitro. It provides a new cell model for the screening and study of anti-hepatic fibrosis drugs.
Subject(s)
Humans , Transforming Growth Factor beta1/pharmacology , Hepatic Stellate Cells/pathology , Liver Cirrhosis/genetics , Collagen Type I/pharmacology , RNA, Messenger/metabolismABSTRACT
The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.
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Abstract@#The prevalence of mental health problems in children and adolescents has been gradually increasing, which has become an important public health problem related to the future of the country and the nation. However, mental disorder rarely exists independently, and comorbidity often occurs, which brings great harm and burden to individuals, families and society. This study introduces the prevalence, burden, characteristics and manifestations of different types of comorbidity with mental disorders as the core. Then it explaines the main causes and mechanisms of comorbidity, and proposes future research directions.
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Objective@#To understand the early life factors that influence cardiometabolic risk factors in children and adolescents, so as to provide effective measures to curb cardiometabolic risk factors such as hypertension and diabetes in children and adolescents.@*Methods@#Data were sourced from the 2020 follow up survey of the Xiamen Adolescent Development Cohort. The study involved 1 197 subjects for whom completed anthropometric examination and blood biochemistry testing data, as well as early life data. Early life and sociodemographic data were obtained through questionnaire surveys, while cardiometabolic indicator data were sourced through physical examinations and blood testing. Logistic regression analysis was performed to analyze the impact of early life factors on the cardiometabolic risk factors after adjusting for gender, age, and family history.@*Results@#The prevalence rate of cardiometabolic risk factors clustering in children and adolescents in Xiamen was 17.96%, with boys (26.67%) reporting higher rates than girls (9.64%), and the difference was statistically significant ( χ 2=57.69, P <0.01). For every additional early life risk factor, the risk factors of obesity increased 0.35 times ( OR=1.35, 95%CI=1.03-1.78, P <0.05). Post term pregnancy may be a primary early life risk factors for cardiometabolic risk factors, and it was associated with an increased risk of cardiometabolic risk factors clustering (OR=2.45, 95% CI =1.11-5.41) and high triglycerides ( OR=3.25, 95%CI =1.39-7.61)( P <0.05).@*Conclusion@#Increased cardiometabolic risk factors in youth is associated with early life adverse factors. It is crucial to pay greater attention to post term pregnancy as an early life factor and to consider obesity as a cardiometabolic risk factors. Controlling early life adverse factors is important for the prevention of cardiovascular disease.
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Objective@#To investigate the prevalence of Internet addiction and depression of students, and to analyze the co-occurrence and trend, so as to provide a theoretical basis for prevention and controlling measures of Internet addiction and depression.@*Methods@#A total of 6 317,7 152,81 808,71 180 and 89 932 students aged 10 to 24 years from 12 leagues (103 banners) in Inner Mongolia Autonomous Region were selected by stratified random cluster sampling in September each year from 2017 to 2021. The Internet Addiction Scale and the Central for Epidemiologic Studies Depression Scale(CES-D) was used to measure Internet addiction and depression. And the annual inspection rate, group difference and annual change trend in students were calculated. Multivariate linear regression and restricted cubic spline analysis were used to estimate the linear and non linear associations between Internet addiction and depression in students.@*Results@#The Internet addiction proportion in students gradually decreased from 4.1% in 2017 to 2.1% in 2020, but increased to 3.9% in 2021. And the depressive symptoms proportion increased from 20.9% in 2017 to 28.0% in 2020 and 27.0% in 2021. The detection rate of Internet addiction and depression comorbidities remained at 1.8% to 2.5 %. The Internet addiction proportion in boys was higher than that in girls( χ 2=42.82, P <0.05). The depressive symptoms prevalence in girls was higher than that in boys( χ 2= 553.90, P <0.05). Taking reversal in prevalence of Internet addiction in urban and rural areas was observed in 2019. The detection rates of depressive symptoms and comorbidity were higher in urban areas than these in suburban counties on the whole, and the difference showed a trend of decreasing or even equalizing year by year. Internet addiction was positively correlated with depressive symptoms score ( B=1.67, 95%CI =1.64-1.71), the proportion of depressive symptoms ( OR=1.39, 95%CI =1.38-1.41) and the proportion of major depressive symptoms ( OR=1.35, 95%CI =1.33-1.36) among students in 2021 ( P <0.05). An N-shaped curve was found in the significant nonlinear associations between internet addiction and depression across sex, region and school stage.@*Conclusion@#Internet addiction and depression in students show significant linear and non-linear associations, which are consistent in different sexes, regions and school stages. Therefore, relevant measures should be made and implemented in each region, especially in suburb areas, so as to prevent the increasingly development of adolescents and children s Internet addiction and depression.
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Objective@#To explore the epidemiological trend of overweight and obesity, elevated blood pressure and their comorbidities in children and adolescents from Inner Mongolia Autonomous Region during 2016-2021, and to analyze its association with lifestyle, so as to provide reference for formulating prevention and control strategies of regional common comorbidities in schools.@*Methods@#A total of 8 908, 8 222, 9 448, 127 068, 100 778, and 138 540 students aged 10-18 years in Inner Mongolia were selected by stratified random cluster sampling in September each year from 2016 to 2021. Physical examination and questionnaire survey were conducted on the included students. The prevalence trends of overweight,obesity, elevated blood pressure and their co-occurrence were analyzed. Logistic regression was used to compare the prevalence of elevated blood pressure in different body mass index (BMI) groups. After excluding individuals without lifestyle information in 2021, Logistic regression analysis was used on 136 374 subjects to analyze the association between overweight,obesity, elevated blood pressure and their co-occurrence and lifestyle factors.@*Results@#During 2016 to 2021, the prevalence of comorbidity of overweight, obesity with elevated blood pressure among students in Inner Mongolia Autonomous Region were 5.04%,5.14%,4.99%,7.51%,7.60% and 9.45%, respectively . The prevalence of overweight and obesity was 26.94%, 28.07%, 29.62%, 34.19%, 36.71% and 37.53%, respectively. The prevalence of elevated blood pressure were 16.05%, 11.54%, 13.12%, 14.85%, 14.12% and 18.40%, respectively. Except for 2016, the risk of elevated blood pressure in overweight and obese people was higher than that in normal BMI group in other years, and there was a positive correlation between overweight and obesity and elevated blood pressure after gender and urban and rural areas ( P < 0.05 ). In 2021, the detection rate of comorbidity of overweight and obesity with elevated blood pressure among children and adolescents in urban areas was higher than that in suburban counties, and the reporting rate of healthy lifestyle was lower than that in suburban counties ( P <0.05).Skipping breakfast ( OR =1.11,95% CI =1.07-1.16) and non daily moderate and high intensity physical activity( OR =1.27,95% CI =1.20-1.34) were positively correlated with the co-occurrence of overweight,obesity and elevated blood pressure among children and adolescents in Inner Mongolia Autonomous Region. Non daily moderate and high intensity physical activity ≥60 min was positively correlated with elevated blood pressure ( OR =1.11,95% CI =1.07-1.16), and insufficient sleep was positively correlated with overweight,obesity ( OR =1.04, 95% CI =1.01-1.06)( P <0.05).@*Conclusion@#The prevalence of overweight,obesity, elevated blood pressure and their co-occurrence among children and adolescents in Inner Mongolia Autonomous Region is relatively high. Overweight/obesity is an important risk factor for elevated blood pressure, and unhealthy lifestyles are risk factors for co-occurrence of overweight,obesity and elevated blood pressure. Region specific lifestyle interventions are indispensable for the prevention and control of regional common comorbidities. Urban areas may be a key focus for lifestyle interventions.
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Objective:To explore the clinical characteristics and treatment regimens of adrenal incidentaloma (AI) in children.Methods:Clinical data of 38 children with AI treated in the Department of Urology, Children′s Hospital of Nanjing Medical University from December 2016 to October 2021 were retrospectively analyzed.A total of 38 children were divided into neonatal group and non-neonatal group according to their age at first diagnosis.The neonatal group had 7 males and 9 females patients, of whom 7 cases were detected with AI during prenatal examinations, 9 cases were diagnosed postnatally.Four children in neonatal group had AI in the left adrenal gland and 12 cases in the right, with the maximum diameter of tumor (MDT) ranging from 16-48 mm.In the non-neonatal group, there were 14 males and 8 females patients aged 7 months and 1 day to 12 years and 1 month, and the MDT was 29-131 mm.Paired t test was used to compare the age and MDT of benign and malignant tumors. Results:In the neonatal group, 3 patients were surgically treated, with 2 cases and 1 case of neuroblastoma and teratoma confirmed by postoperative histology, respectively.The remaining 13 patients in the neonatal group were followed up for 1-31 months, with 8 cases and 5 cases of complete remission and significantly decreased tumor volume, respectively.In the non-neonatal group, there were 3, 9 and 10 patients received open biopsy, laparoscopic adrenalectomy, and open adrenalectomy, respectively.Of these 22 surgically treated cases, 8 cases had a benign lesion, including ganglioneuroma ( n=4), adrenocortical adenoma ( n=1), adrenal cyst ( n=1), teratoma ( n=1), and pheochromocytoma ( n=1); while 14 cases had a malignant lesion, including neuroblastoma ( n=8), ganglioneuroblastoma ( n=5), and adrenocortical carcinoma ( n=1). The mean age of patients with malignant tumors was significantly younger than those with benign tumors[(38.94±35.44) months vs.(95.89±41.43) months, t=3.63, P=0.001]. The mean MDT in malignant tumors was significantly longer than that of benign tumors[(64.43±25.20) mm vs.(41.44±15.66) mm, t=2.45, P=0.023]. Conclusions:AI in children has a high risk of malignancy.Therefore, more detailed examinations are needed to detect tumor markers and endocrinological parameters, and imaging tests such as non-contrast and CT examination should be performed as early as possible.AI in children is predominantly neuroblastic tumors.For non-neonatal patients, surgery should be performed as early as possible.For AI found in the neonatal period and prenatal examination, expectant management is feasible if the tumor is relatively small and limited to the adrenal gland without distant metastases.
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Objective: To investigate the predictive value of glycosylated hemoglobin A1c/apolipoprotein A-1 (HbA1c/ApoA-1) ratio for major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS). Methods: The present study is a retrospective cohort study. ACS patients who were hospitalized and underwent coronary angiography at Beijing Hospital from March 2017 to March 2019 were enrolled. Baseline information such as sex, age, previous history, Gensini score, HbA1c and ApoA-1 were analyzed. Patients were divided into two groups according to presence or absence of MACEs and the difference on HbA1c/ApoA-1 ratio was compared between the two groups. According to the tertiles of HbA1c/ApoA-1 levels, patients were divided into high (5.87-16.12), medium (4.50-5.83) and low (2.11-4.48) HbA1c/ApoA-1 groups. Cox proportional risk model was used to evaluate the differences in MACEs and all-cause mortality among the three groups. Kaplan-Meier survival analysis was used to compare the differences of MACEs between the various HbA1c/ApoA-1 groups. Results: A total of 366 ACS patients were included in this study. The mean age of the patients was (65.9±10.3) years. There were 59 MACEs and 10 all-cause deaths during the mean of (22.3±4.4) months follow-up. After adjusting for age, systolic blood pressure, history of diabetes and Gensini score, the incidence of MACEs was 2.45 times higher in the high HbA1c/ApoA-1 group than in the low HbA1c/ApoA-1 group (95%CI 1.16-5.18, P=0.019). There was no significant difference in all-cause mortality between the high and low HbA1c/ApoA-1 groups (P=1.000). Kaplan-Meier survival analysis showed that patients in the high HbA1c/ApoA-1 group had the highest risk of MACEs, while patients in the low HbA1c/ApoA-1 group had the lowest risk of MACEs (P<0.01). Spearman rank correlation analysis showed that HbA1/ApoA-1 ratio was positively correlated with Gensini score in ACS patients (r=0.274, P<0.01). Conclusion: High HbA1c/ApoA-1 ratio was an independent risk factor for MACEs in ACS patients. Patients with high HbA1c/ApoA-1 ratio had more severe coronary artery disease lesions. HbA1c/ApoA-1 ratio may be used as a potential risk stratification biomarker for ACS patients, it might be useful for the early identification of high-risk population and for predicting the incidence of MACEs among ACS patients.
Subject(s)
Aged , Humans , Middle Aged , Acute Coronary Syndrome/diagnosis , Apolipoprotein A-I/analysis , Biomarkers/analysis , Glycated Hemoglobin/analysis , Percutaneous Coronary Intervention , Retrospective Studies , Risk Factors , Predictive Value of TestsABSTRACT
Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.
Subject(s)
Pregnancy , Female , Humans , Male , Vas Deferens/abnormalities , Azoospermia/surgery , Epididymis/surgery , Retrospective Studies , Tertiary Care Centers , China , SemenABSTRACT
Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Subject(s)
Male , Humans , Prostate-Specific Antigen , Treatment Outcome , Prostatic Neoplasms, Castration-Resistant/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Retrospective StudiesABSTRACT
OBJECTIVE@#To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes.@*METHODS@#The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score.@*RESULTS@#A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect.@*CONCLUSION@#Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.
Subject(s)
Humans , Cell Cycle , Multiple Myeloma/genetics , Prognosis , Risk FactorsABSTRACT
Diabetic retinopathy(DR)is the main cause of substantial visual impairment of occupational active individuals in the world, which has become one of the most common eye diseases that lead to irreversible visual impairment of the working population. Precise identification and accurate intervention of early DR lesions are of great significance to block or delay the development of this disease. Recent studies have shown that DR nerve injury occurs before retinal microangiopathy, it has a series of characteristic clinical manifestations, such as dark adaptation delay, contrast sensitivity and decreased tone discrimination. These characteristic clinical manifestations are key events in the early stage of DR, which are closely related to apoptosis, glial cell proliferation, oxidative stress, inflammation, excitotoxicity of glutamate and imbalance of neurotrophic factors. In this paper, the research progress of DR nerve damage and its related factors are reviewed in order to provide new ideas for the prevention and treatment of DR.
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OBJECTIVE@#To explore the role of ferroptosis-related genes in multiple myeloma(MM) through TCGA database and FerrDb, and build a prognostic model of ferroptosis-related genes for MM patients.@*METHODS@#Using the TCGA database containing clinical information and gene expression profile data of 764 patients with MM and the FerrDb database including ferroptosis-related genes, the differentially expressed ferroptosis-related genes were screened by wilcox.test function. The prognostic model of ferroptosis-related genes was established by Lasso regression, and the Kaplan-Meier survival curve was drawn. Then COX regression analysis was used to screen independent prognostic factors. Finally, the differential genes between high-risk and low-risk patients were screened, and enrichment analysis was used to explore the mechanism of the relationship between ferroptosis and prognosis in MM.@*RESULTS@#36 differential genes related to ferroptosis were screened out from bone marrow samples of 764 MM patients and 4 normal people, including 12 up-regulated genes and 24 down-regulated genes. Six prognosis-related genes (GCLM, GLS2, SLC7A11, AIFM2, ACO1, G6PD) were screened out by Lasso regression and the prognostic model with ferroptosis-related genes of MM was established. Kaplan-Meier survival curve analysis showed that the survival rate between high risk group and low risk group was significantly different(P<0.01). Univariate COX regression analysis showed that age, sex, ISS stage and risk score were significantly correlated with overall survival of MM patients(P<0.05), while multivariate COX regression analysis showed that age, ISS stage and risk score were independent prognostic indicators for MM patients (P<0.05). GO and KEGG enrichment analysis showed that the ferroptosis-related genes was mainly related to neutrophil degranulation and migration, cytokine activity and regulation, cell component, antigen processing and presentation, complement and coagulation cascades, haematopoietic cell lineage and so on, which may affect the prognosis of patients.@*CONCLUSION@#Ferroptosis-related genes change significantly during the pathogenesis of MM. The prognostic model of ferroptosis-related genes can be used to predict the survival of MM patients, but the mechanism of the potential function of ferroptosis-related genes needs to be confirmed by further clinical studies.
Subject(s)
Humans , Multiple Myeloma , Ferroptosis , Prognosis , Hematopoietic System , Blood CoagulationABSTRACT
Robotic surgery revolutionized minimally invasive surgery including kidney transplantation. Robot-assisted kidney transplantation(RAKT) has emerged as an alternative for kidney transplantation. RAKT from living donor kidney is a safe and feasible alternative to open kidney transplantation with less surgical complications without compromising renal function, graft and patient survival. The RAKT approach is promising with widespread use in the future.
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Objective:To explore the clinical value of single-hole laparoscopic percutaneous extraperitoneal closure operation using a Kirschner wire assisted double-hook water-injection hernia needle in treating complicated pediatric oblique inguinal hernia.Methods:The clinical data of 366 children with oblique inguinal hernia treated in the Department of Urology Surgery, Children′s Hospital of Nanjing Medical University from December 2020 to October 2021 were retrospectively analyzed.According to the surgical methods, the children were divided into the ordinary crochet needle group and the Kirschner wire assisted group.Children treated by a single-port laparoscopic double hook water-injection hernia crochet needle (309 cases) were classified into the ordinary crochet needle group.Children treated by a single-port laparoscopic Kirschner wire assisted double hook water-injection hernia crochet needle (57 cases) were included in the Kirschner wire assisted group.The independent sample t-test and rank sum test was used to compare the relevant clinical indicators between the two groups. Results:Compared with the ordinary crochet needle group, children in the Kirschner wire assisted group were younger at surgery[(2.87±1.88) years vs.(4.91±2.39) years] and had larger hernia sacs [17 303.89(8 622.49, 37 295.42) mm 3vs.9 650.97(3 849.24, 17 539.51) mm 3]. The differences in the age at surgery and hernia sac volume were statistically significant ( t=-5.407, Z=-4.218; all P<0.001). There was no significant difference in body mass index between the 2 groups ( P>0.05). Taking hernias with sac volume >10 000 mm 3 as huge hernias, there were 70.18%(40/57 cases) and 47.25%(146/309 cases) of huge hernias in the Kirschner wire assisted group and the ordinary crochet needle group, respectively.The overall operation time of the Kirschner wire assisted group was significantly longer than that of the ordinary crochet needle group[(20(15, 20) min vs.15(15, 20) min] ( Z=-2.842, P<0.05). However, the operation time for huge oblique hernias with sac volume >10 000 mm 3 was not statistically significant between the 2 groups ( P>0.05). No recurrence in both groups was found during 6-16 months of follow-up. Conclusions:For complicated oblique inguinal hernia in children with a huge hernia or obvious retroperitoneal folds at the internal ring and heavy scar adhesion between the hernia sac and abdominal wall, the insertion of a Kirschner wire can help the hernia crochet needle to traverse the vas de-ferens and spermatic cord vessels smoothly.As a single port laparoscopic operation, the Kirschner wire assisted hernia crochet needle requires no addition of trocar holes and leaves only a small surgical scar.With good feasibility and safety, it is applicable for clinical popularization.
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BACKGROUND@#There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.@*METHODS@#From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n = 72) or allo-HSCT (n = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.@*RESULTS@#Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).@*CONCLUSIONS@#Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.
Subject(s)
Humans , China , Hematopoietic Stem Cell Transplantation , Lymphoma, T-Cell, Peripheral/therapy , Neoplasm Recurrence, Local , Retrospective Studies , Transplantation, Autologous , Transplantation, Homologous , Treatment OutcomeABSTRACT
OBJECTIVE@#To analyze clinical effectiveness of myelodysplastic syndrome (MDS) patients treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to investigate new therapy strategy for the treatment of relapse after allo-HSCT.@*METHODS@#72 MDS patients treated by HSCT in our hospital from April 2013 to November 2019 were enrolled and analyzed retrospectively. The effect of allo-HSCT was summarized. The risk factors affecting the survival and relapse of the patients were investigated.@*RESULTS@#Among 72 patients, the median follow up was 37(12-111) months. 57 patients survived(79.2%),while 15 patients died(20.8%). The 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate were 76.6% and 62.3%, respectively. IPSS-R, TP53 mutation and chronic graft versus-host-disease (cGVHD) were the risk factors affecting the OS of the MDS patients after treated by allo-HSCT. IPSS-R, TP53 mutation and Ⅲ-Ⅳ° acute graft versus-host-disease (aGVHD) were the risk factors affecting the DFS of the MDS patients after treated by allo-HSCT. After transplanted, 19 patients (26.4%) emerged aGVHD, and 5 patients (6.9%) emerged Ⅲ-Ⅳ° aGVHD, 25 patients (34.7%) emerged cGVHD, while 4 patients (5.6%) emerged extensive cGVHD. 17 patients (23.3%) relapsed, and the 5-year cumulative incidence of relapse (CIR) rate was 27.5%. IPSS-R, TP53 mutation and cGVHD were the risk factors affecting the relapse of the patients. The median survival time after relapse was 9 months. There were 7 out of 17 relapsed patients survived without disease, while 10 patients died. The OS rate of patients treated with maintained hypomethylation agents(HMA) combined with G-CSF mobilized donor lymphocyte infusion (DLI) was significantly higher than the patients without HMA (80.0% vs 10.0%, P=0.002).@*CONCLUSION@#Allo-HSCT is an effective therapy for intermediate and high risk MDS patients. But relapse after HSCT is still a major problem that affecting the survival of the patients. Maintenance treatment of HMA combined with DLI may improve the long-time survival of MDS patients with relapsed after treated by allo-HSCT.