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Objective: To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice. Methods: This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed. Results: A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up. Conclusions: MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.
Subject(s)
Catheter Ablation , Hemodynamics , Tachycardia, Ventricular , Humans , Tachycardia, Ventricular/surgery , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/therapy , Retrospective Studies , Catheter Ablation/methods , Treatment Outcome , Extracorporeal Membrane Oxygenation/methods , Heart-Assist Devices , Male , Female , Middle AgedABSTRACT
Mutations in the lysosomal membrane protein CLN3 cause Juvenile Neuronal Ceroid Lipofuscinosis (JNCL). Activation of the lysosomal ion channel TRPML1 has previously been shown to be beneficial in several neurodegenerative disease models. Here, we tested whether TRPML1 activation rescues disease-associated phenotypes in CLN3-deficient retinal pigment epithelial (ARPE-19 CLN3-KO) cells. ARPE-19 CLN3-KO cells accumulate LAMP1 positive organelles and show lysosomal storage of mitochondrial ATPase subunit C (SubC), globotriaosylceramide (Gb3), and glycerophosphodiesters (GPDs), whereas lysosomal bis(monoacylglycero)phosphate (BMP/LBPA) lipid levels were significantly decreased. Activation of TRPML1 reduced lysosomal storage of Gb3 and SubC but failed to restore BMP levels in CLN3-KO cells. TRPML1-mediated decrease of storage was TFEB-independent, and we identified TRPML1-mediated enhanced lysosomal exocytosis as a likely mechanism for clearing storage including GPDs. Therefore, ARPE-19 CLN3-KO cells represent a human cell model for CLN3 disease showing many of the described core lysosomal deficits, some of which can be improved using TRPML1 agonists.
Subject(s)
Lysosomes , Membrane Glycoproteins , Molecular Chaperones , Neuronal Ceroid-Lipofuscinoses , Retinal Pigment Epithelium , Transient Receptor Potential Channels , Lysosomes/metabolism , Humans , Retinal Pigment Epithelium/metabolism , Molecular Chaperones/metabolism , Molecular Chaperones/genetics , Membrane Glycoproteins/metabolism , Membrane Glycoproteins/genetics , Neuronal Ceroid-Lipofuscinoses/metabolism , Neuronal Ceroid-Lipofuscinoses/genetics , Neuronal Ceroid-Lipofuscinoses/pathology , Transient Receptor Potential Channels/metabolism , Transient Receptor Potential Channels/genetics , Phenotype , Cell Line , Exocytosis , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Lysophospholipids , MonoglyceridesABSTRACT
Objective: To assess the efficacy and safety of flexible ureteral lithotripsy (FURL) for treating upper urinary tract calculi in patients ≥80 years. Methods: This study retrospectively analyzed the clinical data of 297 elderly patients who underwent FURL for unilateral upper urinary tract calculi at Beijing Hospital from January 2019 to September 2023. Patients were divided into elderly group (≥80 years) and low-middle aged group (≥60-<80 years). Propensity score matching (PSM) was used to match preoperative clinical data of patients. After PSM, the basic, perioperative and postoperative data of the two groups were compared. Results: After PSM, 116 patients were enrolled, including 58 patients in each group. The age [M (Q1, Q3)] of elderly group was 83.0 (81.0, 86.0) years, which included 29 males. The age of low-middle aged group was 69.5 (64.8, 74.0) years, which included 33 males. The duration of postoperative hospitalization [M (Q1, Q3)] in elderly group was longer than that in low-middle aged group [2 (1, 3) d vs 1 (1, 2) d, P=0.002]. Serious postoperative complications occurred in 3 cases in the elderly group and 1 case in the low-middle aged group, respectively, without surgical intervention. There was no significant statistical difference in stone-free rate (SFR) [79.3% (46/58) vs 84.5% (49/58)], operation time [M (Q1, Q3), 70.0 (48.3, 100.0) vs 65.0 (46.5, 101.2) min] and postoperative complication rate [25.9% (15/58) vs 22.4% (13/58)] between two groups (all P>0.05). Conclusions: In the treatment of upper urinary tract calculi in patients ≥80 years, the SFR, operation time and postoperative complication rate of FURL are comparable to those in low-middle aged elderly patients. FURL has good safety and effectiveness in the treatment of upper urinary tract calculi in patients ≥80 years.
Subject(s)
Lithotripsy , Humans , Male , Retrospective Studies , Female , Lithotripsy/methods , Aged, 80 and over , Treatment Outcome , Aged , Ureteral Calculi/therapy , Urinary Calculi/therapy , Propensity Score , Middle Aged , Postoperative ComplicationsABSTRACT
PURPOSE: Parastomal hernia poses a challenging problem in the field of hernia surgery. The high incidence and recurrence rates of parastomal hernia necessitate surgeons to enhance surgical techniques and repair materials. This study aimed to develop a rat model of parastomal hernia by inducing various types of defects on the abdominal wall with colostomy. This established method has potential for future studies on parastomal hernia. METHODS: In this study, 32 male rats were included and randomly divided into four groups: the oblique abdominis excision (OE), oblique abdominis dissection (OD), rectus abdominis excision (RE), and rectus abdominis dissection (RD) groups. In each group, colostomy was performed and an abdominal wall defect was induced. The rats were observed for 28 days following surgery. The survival rate, body weight, parastomal hernia model scores, abdominal wall adhesion and inflammation, and collagen level in the hernial sac were compared. RESULTS: No significant differences in survival rate and weight were observed among the four groups. The parastomal hernia model scores in the RE and RD groups were significantly higher than those in the OE and OD groups. The ratio of collagen I/III in the RE and RD groups was significantly lower than that in the OE and OD groups. Adhesion and inflammation levels were lower in the RE group than in the RD group. CONCLUSION: Based on a comprehensive comparison of the findings, RE with colostomy emerged as the optimal approach for establishing parastomal hernia models in rats.
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This project was undertaken to develop the first set of consensus statements regarding the management of pancreatic ductal adenocarcinoma (PDAC) in Hong Kong, with the goal of providing guidance to local clinicians. A multidisciplinary panel of experts discussed issues surrounding current PDAC management and reviewed evidence gathered in the local context to propose treatment recommendations. The experts used the Delphi approach to finalise management recommendations. Consensus was defined as ≥80% acceptance among all expert panel members. Thirty-nine consensus statements were established. These statements cover all aspects of PDAC management, including diagnosis, resectability criteria, treatment modalities according to resectability, personalised management based on molecular profiling, palliative care, and supportive care. This project fulfils the need for guidance regarding PDAC management in Hong Kong. To assist clinicians with treatment decisions based on varying levels of evidence and clinical experience, treatment options are listed in several consensus statements.
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Objective: To understand the incidence of diabetes and influencing factors, the trend of FPG change and risk for mortality in HIV-infected individuals after antiretroviral therapy (ART) in Dehong Dai and Jingpo Autonomous Prefecture (Dehong). Methods: The HIV/AIDS treatment database was collected from China Information System for Disease Control and Prevention. This retrospective cohort study was conducted in HIV-infected individuals with access to ART in Dehong during 2004-2020.The Cox proportional hazard regression model was used to analyze the incidence density of diabetes, the influencing factors and risk for mortality in HIV-infected individuals with access to ART, mixed linear effects model was used to analyze the trend of FPG change and predict FPG in those with different glucose metabolic status at baseline survey. Statistical analysis was performed using software SAS 9.4. Results: A total of 8 763 HIV-infected individuals were included, in whom 8 432 (96.2%) had no diabetes, 331 had diabetes. The incidence density of diabetes was 2.31/1 000 person years. Multivariate Cox proportional hazard regression analysis revealed that 30- 59 years old, BMI ≥24.0 kg/m2, Efavirenz (EFV) based initial treatment regimen and impaired fasting glucose (IFG) at baseline survey were significantly and positively associated with incidence of diabetes. Mixed effect model revealed that FPG was positively correlated with the duration of ART, age and baseline FPG. Suffering from diabetes was a risk factor for mortality in HIV-infected individuals both at baseline survey and during follow-up. Conclusions: The risk for diabetes increased in HIV-infected individuals who were 30-59 years old, baseline BMI ≥24.0 kg/m2, received EFV based initial treatment, and IFG in HIV-infected individuals after antiretroviral therapy in Dehong, 2004-2020. It is important to pay close attention to their blood glucose, and patients with high blood glucose should receive treatment as early as possible.
Subject(s)
Diabetes Mellitus , HIV Infections , Humans , Adult , Middle Aged , Incidence , Blood Glucose , Retrospective Studies , HIV Infections/drug therapy , HIV Infections/epidemiology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/epidemiology , China/epidemiologyABSTRACT
OBJECTIVE: This study aimed to compare the efficacy and safety of oral and transdermal estradiol in alleviating menopausal symptoms. METHOD: A total of 257 recently menopausal women were randomized into two groups. The t-E2 group received transdermal estradiol (2.5 g per day) (n = 128) and the o-E2V group received oral estradiol valerate (2 mg per day) (n = 129) for 24 weeks; both groups received micronized progesterone (200 mg per day). The primary outcome measure is the change in the modified Kupperman Menopausal Index (KMI) after 24 weeks of treatment. Menopausal symptoms were recorded at screening and at 4, 12 and 24 weeks using both the KMI and the Menopause Rating Scale (MRS). RESULTS: Significant amelioration was observed by KMI and MRS scores for both groups after treatment (p < 0.001). The mean KMI scores showed no difference between the two groups. The mean MRS scores were similar between the two groups at baseline and after 4 weeks of treatment. The results showed statistical differences after 12 weeks and 24 weeks of treatment (p = 0.005 and p = 0.011). Both the after-treatment scores minus the baseline scores of KMI and MRS and the incidence of adverse effects showed no difference between the two groups. CONCLUSIONS: This study shows that both transdermal and oral estradiol are effective in relieving menopausal symptoms, with little difference in treatment efficacy and safety. CLINICAL TRIAL NUMBER: ChiCTR2300073146.
Subject(s)
Estradiol , Menopause , Female , Humans , Progesterone , Estrogen Replacement Therapy/methods , Treatment Outcome , Administration, CutaneousABSTRACT
Adipose tissue is an active endocrine organ that can signal bidirectionally to many tissues and organ systems in the body. With obesity, adipose tissue is a source of low-level inflammation that contributes to various co-morbidities and damage to downstream effector tissues. The ability to synthesize genetically engineered adipose tissue could have critical applications in studying adipokine signaling and the use of adipose tissue for novel therapeutic strategies. This study aimed to develop a method for non-viral adipogenic differentiation of genome-edited murine induced pluripotent stem cells (iPSCs) and to test the ability of such cells to engraft in mice in vivo . Designer adipocytes were created from iPSCs, which can be readily genetically engineered using CRISPR-Cas9 to knock out or insert individual genes of interest. As a model system for adipocyte-based drug delivery, an existing iPSC cell line that transcribes interleukin 1 receptor antagonist under the endogenous macrophage chemoattractant protein-1 promoter was tested for adipogenic capabilities under these same differentiation conditions. To understand the role of various adipocyte subtypes and their impact on health and disease, an efficient method was devised for inducing browning and whitening of IPSC-derived adipocytes in culture. Finally, to study the downstream effects of designer adipocytes in vivo , we transplanted the designer adipocytes into fat-free lipodystrophic mice as a model system for studying adipose signaling in different models of disease or repair. This novel translational tissue engineering and regenerative medicine platform provides an innovative approach to studying the role of adipose interorgan communication in various conditions.
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INTRODUCTION: Patients with pancreatic cancer have a high risk of thromboembolism (TE), which may increase mortality. Most relevant studies have been conducted in Western populations. We investigated risk factors for TE in a predominantly Chinese population of patients with pancreatic cancer, along with effects of TE on overall survival. METHODS: This retrospective cohort study included patients diagnosed with exocrine pancreatic cancer in Prince of Wales Hospital in Hong Kong between 2010 and 2015. Data regarding patient demographics, World Health Organization performance status, stage, treatment, TE-related information, and time of death (if applicable) were retrieved from electronic medical records. Univariate and multivariable logistic regression analyses were performed to identify risk factors for TE. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: In total, 365 patients were included in the study. The overall incidence of TE (14.8%) was lower than in Western populations. In univariate logistic regression analysis, stage IV disease and non-head pancreatic cancer were significantly associated with TE (both P=0.01). Multivariable logistic regression analysis showed that stage IV disease was a significant risk factor (odds ratio=1.08, 95% confidence interval [CI]=1.00-1.17; P=0.046). Median overall survival did not significantly differ between patients with and without TE (4.88 months vs 7.80 months, hazard ratio=1.08, 95% CI=0.80-1.49; P=0.58) and between patients with TE who received anticoagulation treatment or not (5.63 months vs 4.77 months, hazard ratio=0.72, 95% CI=0.40-1.29; P=0.27). CONCLUSION: The incidence of TE was low in our Chinese cohort. Stage IV disease increased the risk of TE. Overall survival was not affected by TE or its treatment.
Subject(s)
Pancreatic Neoplasms , Thromboembolism , Humans , Retrospective Studies , Thromboembolism/epidemiology , Thromboembolism/etiology , Thromboembolism/diagnosis , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/epidemiology , Risk Factors , Pancreatic NeoplasmsABSTRACT
Objective: Explore the association between atrial fibrillation (AF) reoccurrence and new-onset ischemic stroke (IS) in patients with nonvalvular AF, and explore whether there is a high-risk period of IS after recurrent episodes of AF. Methods: A nested case-control study design was used. A total of 565 nonvalvular AF patients with new-onset IS after a follow-up of at least 2 years in the China-AF cohort were enrolled as the case group, and 1 693 nonvalvular AF patients without new-onset IS were matched as the control group at a ratio of 1â¶3. Frequency and types of recurrent AF in the previous 1 or 2 years were compared between two groups, and the adjusted associations of AF reoccurrence with new onset IS were explored using conditional logistic regression analysis. The proportion of recurrent AF was compared between the case period and control period, and conditional logistic regression analysis was performed to calculate adjusted associations of case-period AF with IS. Results: The nested case-control study design results showed that the proportion of at least one record of recurrent AF in the previous 1 year was higher in the case group than in the control group (72.0% vs. 60.8%, P<0.05), and the recurrent AF was positively correlated with new-onset IS (adjusted OR=1.80, P<0.001). Similar results were also observed in the previous 2 years period. The case-crossover study design analysis showed that among 565 patients with new-onset IS, recurrent AF in the case period was positively correlated with IS (adjusted OR=1.61, P=0.003). Conclusion: Recurrent AF is associated with IS, and there may be a high-risk period of IS after recurrent episodes of AF.
Subject(s)
Atrial Fibrillation , Ischemic Stroke , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/epidemiology , Case-Control Studies , Cross-Over Studies , China/epidemiologyABSTRACT
Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3ß phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.
Subject(s)
Crohn Disease , Inflammatory Bowel Diseases , Child , Male , Humans , Female , Child, Preschool , Adolescent , Colon , Inflammation , Colonoscopy , Glycoproteins , Wnt ProteinsABSTRACT
Helicobacter pylori infection causes chronic gastric inflammation that contributes to various gastroduodenal diseases, including peptic ulcer and gastric cancer. Despite broad regional variations, the prevalence of resistance to antibiotics used to manage H pylori infection is increasing worldwide; this trend could hinder the success of eradication therapy. To increase awareness of H pylori and improve the diagnosis and treatment of its infection in Hong Kong, our consensus panel proposed a set of guidance statements for disease management. We conducted a comprehensive review of literature published during 2011 and 2021, with a focus on articles from Hong Kong or other regions of China. We evaluated the evidence using the Oxford Centre for Evidence-Based Medicine's 2011 Levels of Evidence and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system and sought consensus through online voting and a subsequent face-to-face meeting, which enabled us to develop and refine the guidance statements. This report consists of 24 statements regarding the epidemiology and burden, screening and diagnosis, and treatment of H pylori. Key guidance statements include a recommendation to use the test-and-treat approach for high-risk individuals, as well as the confirmation that triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin remains a valid first-line option for adults and children in Hong Kong.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Adult , Child , Humans , Helicobacter Infections/diagnosis , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Hong Kong/epidemiology , Consensus , Anti-Bacterial Agents/therapeutic useABSTRACT
Objective: To investigate current use of oral anticoagulant (OAC) therapy and influencing factors among coronary artery disease (CAD) patients with nonvalvular atrial fibrillation (NVAF) in China. Methods: Results of this study derived from "China Atrial Fibrillation Registry Study", the study prospectively enrolled atrial fibrillation (AF) patients from 31 hospitals, and patients with valvular AF or treated with catheter ablation were excluded. Baseline data such as age, sex and type of atrial fibrillation were collected, and drug history, history of concomitant diseases, laboratory results and echocardiography results were recorded. CHA2DS2-VASc score and HAS-BLED score were calculated. The patients were followed up at the 3rd and 6th months after enrollment and every 6 months thereafter. Patients were divided according to whether they had coronary artery disease and whether they took OAC. Results: 11 067 NVAF patients fulfilling guideline criteria for OAC treatment were included in this study, including 1 837 patients with CAD. 95.4% of NVAF patients with CAD had CHA2DS2-VASc score≥2, and 59.7% of patients had HAS-BLED≥3, which was significantly higher than NVAF patients without CAD (P<0.001). Only 34.6% of NVAF patients with CAD were treated with OAC at enrollment. The proportion of HAS-BLED≥3 in the OAC group was significantly lower than in the no-OAC group (36.7% vs. 71.8%, P<0.001). After adjustment with multivariable logistic regression analysis, thromboembolism(OR=2.48,95%CI 1.50-4.10,P<0.001), left atrial diameter≥40 mm(OR=1.89,95%CI 1.23-2.91,P=0.004), stain use (OR=1.83,95%CI 1.01-3.03, P=0.020) and ß blocker use (OR=1.74,95%CI 1.13-2.68,P=0.012)were influence factors of OAC treatment. However, the influence factors of no-OAC use were female(OR=0.54,95%CI 0.34-0.86,P=0.001), HAS-BLED≥3 (OR=0.33,95%CI 0.19-0.57,P<0.001), and antiplatelet drug(OR=0.04,95%CI 0.03-0.07,P<0.001). Conclusion: The rate of OAC treatment in NVAF patients with CAD is still low and needs to be further improved. The training and assessment of medical personnel should be strengthened to improve the utilization rate of OAC in these patients.
Subject(s)
Atrial Fibrillation , Coronary Artery Disease , Stroke , Humans , Female , Male , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Coronary Artery Disease/drug therapy , Coronary Artery Disease/complications , Anticoagulants/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Risk Factors , China , Administration, OralABSTRACT
OBJECTIVE: To investigate the mechanism by which fibroblasts with high WNT2b expression causes intestinal mucosa barrier disruption and promote the progression of inflammatory bowel disease (IBD). METHODS: Caco-2 cells were treated with 20% fibroblast conditioned medium or co-cultured with fibroblasts highly expressing WNT2b, with the cells without treatment with the conditioned medium and cells co-cultured with wild-type fibroblasts as the control groups. The changes in barrier permeability of Caco-2 cells were assessed by measuring transmembrane resistance and Lucifer Yellow permeability. In Caco-2 cells co-cultured with WNT2b-overexpressing or control intestinal fibroblasts, nuclear entry of ß-catenin was detected with immunofluorescence assay, and the expressions of tight junction proteins ZO-1 and E-cadherin were detected with Western blotting. In a C57 mouse model of dextran sulfate sodium (DSS)-induced IBD-like enteritis, the therapeutic effect of intraperitoneal injection of salinomycin (5 mg/kg, an inhibitor of WNT/ß-catenin signaling pathway) was evaluated by observing the changes in intestinal inflammation and detecting the expressions of tight junction proteins. RESULTS: In the coculture system, WNT2b overexpression in the fibroblasts significantly promoted nuclear entry of ß-catenin (P < 0.01) and decreased the expressions of tight junction proteins in Caco-2 cells; knockdown of FZD4 expression in Caco-2 cells obviously reversed this effect. In DSS-treated mice, salinomycin treatment significantly reduced intestinal inflammation and increased the expressions of tight junction proteins in the intestinal mucosa. CONCLUSION: Intestinal fibroblasts overexpressing WNT2b causes impairment of intestinal mucosal barrier function and can be a potential target for treatment of IBD.
Subject(s)
Inflammatory Bowel Diseases , beta Catenin , Humans , Mice , Animals , Caco-2 Cells , beta Catenin/metabolism , Culture Media, Conditioned/pharmacology , Tight Junctions/metabolism , Intestinal Mucosa , Tight Junction Proteins/metabolism , Inflammation/metabolism , Fibroblasts/metabolism , Mice, Inbred C57BL , Glycoproteins/metabolism , Wnt Proteins/metabolism , Wnt Proteins/pharmacology , Frizzled Receptors/metabolismABSTRACT
Objective: To investigate the genetic and genomic profiling of juvenile myelomonocytic leukemia (JMML) and factors affecting its survival rate. Methods: Clinical characteristics, cytogenetics, molecular biology results and survival status of children with 27 JMML cases admitted to the Hematology Department of Children's Hospital, Capital Institute of Pediatrics from December 2012 to December 2021 were analyzed retrospectively, and the outcomes of the children were followed up. Kaplan-Meier method was used for survival analysis. Univariate analysis was used for analyzing factors affecting the overall survival (OS) rates of patients who received hematopoietic stem cell transplantation (HSCT). Log-Rank test was used for comparison of survival curves. Results: Among 27 JMML cases, there were 11 males and 16 females. The age of disease onset was 28 (11,52) months. There are 20 cases of normal karyotype, 4 cases of monosomy 7, 1 case of trisomy 8,1 case of 11q23 rearrangement and 1 case of complex karyotype. A total of 39 somatic mutations were detected.Those involved in RAS signal pathway were the highest (64%(25/39)), among which PTPN11 mutation was the most frequent (44% (11/25)). A total of 17 cases (63%) received HSCT, 8 cases (30%) did not receive HSCT, and 2 cases (7%) lost follow-up. For children receiving transplantation, the follow-up time after transplantation was 47 (11,57) months. The 1-year OS rate of high-risk transplantation group (17 cases) and high-risk non transplantation group (6 cases) was (88±8)% and (50±20)% respectively, with a statistically significant difference (χ2=5.01, P=0.025). The 5-year OS rate of the high-risk transplantation group was (75±11)%. The survival time of those who relapsed or progressed to acute myeloid leukemia after transplantation was significantly shorter than that of those who did not relapse (χ2=6.80, P=0.009). The OS rate of patients with or without PTPN11 mutation was (81±12) % and (67±19)% respectively (χ2=0.85, P=0.356). Conclusions: The main pathogenesis involved in JMML is gene mutation related to RAS signaling pathway, and the most common driver gene of mutation is PTPN11. Allogeneic HSCT can significantly improve the survival rate of high-risk JMML patients. The recurrence or progression after transplantation was related to poor prognosis.
Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myelomonocytic, Juvenile , Male , Female , Child , Humans , Child, Preschool , Leukemia, Myelomonocytic, Juvenile/genetics , Leukemia, Myelomonocytic, Juvenile/therapy , Retrospective Studies , Survival Analysis , MutationABSTRACT
Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
Subject(s)
Allergens , Desensitization, Immunologic , Hypersensitivity , Humans , Asian People , Desensitization, Immunologic/adverse effects , Hypersensitivity/epidemiology , Retrospective StudiesABSTRACT
Objective: To investigate the application of vaseline gauze to occlude the bronchial fistulas and its clinical effectiveness and safety in this retrospective study. Methods: This study retrospectively reviewed the clinical records of 14 patients with bronchial fistulas at Department of Respiratory and Critical Care Medicine, Shanghai Dongfang Hospital affiliated to Tongji University between June 2019 and June 2022. Seven of the 14 patients were female, and the age ranged from 16 to 74 years. We retrieved all the clinical records of all the enrolled patients during the 6 to 12 months follow-up after the operation, including the information for removal of chest drainage pipe, the failure of endobronchial blockage using vaseline gauze, as well as the complications (migration of the vaseline gauze, obstructive pneumonia, pulmonary atelectasis, et. al.) after the operation. Results: Of the 14 patients, 3 patients had fistula located in main or lobar bronchi; 10 patients had fistula located in distal airways; and 1 patient had fistula located both in main bronchi and distal airways. Ten patients were complicated with pneumonia or pleural cavity infections; Five were complicated with pneumothorax or hydropneumothorax. All of the 14 patients achieved successful airway occlusion after the placement of vaseline gauze in the responsible bronchial airways or stumps for the fistulas. Eleven of the 14 patients successfully removed the drainage tube for the residual cavity, 3 of the 14 patients successfully removed the vaseline gauze for the fistula which was healing during the follow up of 6-12 months. No one of the patients had severe complications or treatment failure. Conclusion: Bronchial placement of vaseline gauze might be a feasible and effective technique for treatment of bronchial fistulas.
Subject(s)
Bronchial Fistula , Pneumonia , Humans , Female , Adolescent , Young Adult , Adult , Middle Aged , Aged , Male , Bronchial Fistula/etiology , Petrolatum , Retrospective Studies , ChinaABSTRACT
Nine patients identified as hypertrophic obstructive cardiomyopathy (HOCM) in Beijing Anzhen Hopspital who underwent ablation from March to July 2019 were included in the study. All patients had left ventricular outï¬ow tract gradient (LVOTG) over 50 mmHg(1 mmHg=0.133 kPa)with significant symptoms despite not optimal drug therapy. Intracardiac echocardiography (ICE) was used to reconstruct septum and surrounding structures, and monitor the effect of ablation during procedure. Nine patients with HOCM were included,.of which 6 men and 3 women. The average age was (51.7±12.2) years. All patients underwent successful ablation after a mean of procedural time of (152.2±31.9) minutes and ablation time of (838.4±227.3) seconds. Except for one patients, all other patients had significant LVOTG reduction(P=0.001)within 50 mmHg after the procedure. Systolic anterior motion of the mitral valve disappeared in all patients after the procedure without major periprocedural complications. The LVOTG of these patients remained stable during follow-up. Radiofrequency ablation using ICE guidance is feasible in treating HOCM with promising efficacy and safety.
Subject(s)
Cardiomyopathy, Hypertrophic , Catheter Ablation , Male , Humans , Female , Adult , Middle Aged , Mitral Valve , Echocardiography , HypertrophyABSTRACT
Objective: To compare the differences between CAS risk model and CHA2DS2-VASc risk score in predicting all cause death, thromboembolic events, major bleeding events and composite endpoint in patients with nonvalvular atrial fibrillation. Methods: This is a retrospective cohort study. From the China Atrial Fibrillation Registry cohort study, the patients with atrial fibrillation who were>18 years old were randomly divided into CAS risk score group and CHA2DS2-VASc risk score group respectively. According to the anticoagulant status at baseline and follow-up, patients in the 2 groups who complied with the scoring specifications for anticoagulation were selected for inclusion in this study. Baseline information such as age and gender in the two groups were collected and compared. Follow-up was performed periodically to collect information on anticoagulant therapy and endpoints. The endpoints were all-cause death, thromboembolism events and major bleeding, the composite endpoint events were all-cause death and thromboembolism events. The incidence of endpoints in CAS group and CHA2DS2-VASc group was analyzed, and multivariate Cox proportional risk model was used to analyze whether the incidence of the endpoints was statistically different between the two groups. Results: A total of 5 206 patients with AF were enrolled, average aged (63.6±12.2) years, and 2092 (40.2%) women. There were 2 447 cases (47.0%) in CAS risk score group and 2 759 cases (53.0%) in CHA2DS2-VASc risk score group. In the clinical baseline data of the two groups, the proportion of left ventricular ejection fraction<55%, non-paroxysmal atrial fibrillation, oral warfarin and HAS BLED score in the CAS group were lower than those in the CHA2DS2-VASc group, while the proportion of previous diabetes history and history of antiplatelet drugs in the CAS group was higher than that in the CHA2DS2-VASc group, and there was no statistical difference in other baseline data. Patients were followed up for (82.8±40.8) months. In CAS risk score group, 225(9.2%) had all-cause death, 186 (7.6%) had thromboembolic events, 81(3.3%) had major bleeding, and 368 (15.0%) had composite endpoint. In CHA2DS2-VASc risk score group, 261(9.5%) had all-cause death 209(7.6%) had thromboembolic events, 112(4.1%) had major bleeding, and 424 (15.4%) had composite endpoint. There were no significant differences in the occurrence of all-cause death, thromboembolic events, major bleeding and composite endpoint between anticoagulation in CAS risk score group and anticoagulation in CHA2DS2-VASc risk score group (log-rank P =0.643, 0.904, 0.126, 0.599, respectively). Compared with CAS risk score, multivariable Cox proportional hazards regression models showed no significant differences for all-cause death, thromboembolic events, major bleeding and composite endpoint between the two groups with HR(95%CI) 0.95(0.80-1.14), 1.00(0.82-1.22), 0.83(0.62-1.10), 0.96(0.84-1.11), respectively. All P>0.05. Conclusions: There were no significant differences between CAS risk model and CHA2DS2-VASc risk score in predicting all-cause death, thromboembolic events, and major bleeding events in Chinese patients with non-valvular atrial fibrillation.