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AIM: To evaluate the efficacy of high-intensity focused ultrasound cyclo plasty(UCP)in the treatment of glaucoma and to investigate related influencing factors.METHODS: The study involved a total of 110 patients(134 eyes)who received UCP treatment between January 2019 and January 2022 at three medical centers: Tianjin Eye Aier Eye Hospital, Chongqing Aier Eye Hospital, and Chongqing Nanping Aier Eye Hospital. Patients were classified into three categories: primary angle-closure glaucoma, primary open-angle glaucoma, and secondary glaucoma. Best corrected visual acuity, intraocular pressure, and the usage of anti-glaucoma medications, etc., were recorded at 6 and 12 mo postoperatively.RESULTS: After 6 months of the UCP procedure, statistically significant differences in intraocular pressure were observed across all groups(all P<0.05). At 12 mo postoperatively, intraocular pressure of the primary angle-closure and primary open-angle glaucoma groups showed differences(all P<0.05). Notably, there were no significant changes in visual acuity at either the 6 or 12 mo compared to preoperative values across all patient groups(all P>0.05). Furthermore, the study identified a statistically significant correlation between the changes in intraocular pressure at 6 mo and factors such as age, history of previous glaucoma surgery, baseline white-to-white(corneal diameter), and the extent of UCP treatment(all P<0.05).CONCLUSION: The UCP procedure has been demonstrated to effectively lower intraocular pressure in patients with glaucoma. The efficacy appears to be influenced by variables including patient age, previous glaucoma surgery history, baseline white-to-white(corneal diameter), and the scope of UCP treatment. Importantly, UCP treatment did not adversely affect visual acuity, underscoring its favorable safety profile.
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Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.
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Objective To explore the relationship and internal path between activities of daily living(ADL),sleep quality and mental health of community elderly people in Shanghai.Methods A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec,2021 using convenience sampling.Activities of Daily Living(ADL),Pittsburgh Sleep Quality Index(PSQI)and 10-item Kessler Psychological Distress Scale(K10)were adopted in the survey.Single factor analysis,correlation analysis and multiple linear regression were used to analyze the data.The effect relationship between the variables was tested using Bootstrap's mediated effects test.Results A total of 1 864 participants were included in the study.The average score was 15.53±4.47 for ADL,5.60±3.71 for PSQI and 15.50±6.28 for K10.The rate of ADL impairment,poor sleep quality,poor and very poor mental health of the elderly were 23.6%,27.3%,11.9%and 4.9%,respectively.ADL and sleep quality were all positively correlated with mental health(r=0.321,P<0.001;r=0.466,P<0.001);ADL was positively correlated with sleep quality(r=0.294,P<0.001).Multiple linear results of factors influencing mental health showed that ADL(β= 0.457,95%CI:0.341-0.573),sleep quality(β =0.667,95%CI:0.598-0.737)and mental health were positively correlated(P<0.001).Sleep quality partially mediated the relationship between ADL and mental health(95%CI:0.078-0.124)with an effect size of 33.0%.Conclusion Sleep quality is a mediator between ADL and mental health among community elderly people.Improving ADL and sleep quality may improve mental health in the population.
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Objective To investigate the effect of auditory brainstem response(ABR)in clinical detection and severity assessment of autism spectrum disorder(ASD)in children with normal hearing.Methods ① A total of 55 autistic children(110 ears)with normal hearing and 55 children(110 ears)with typical development(TD)who did not differ in sex composition ratio and average monthly age were divided into four sub-groups according to age:≤24 months group(22 ears),25~36 months group(40 ears),37~48 months group(28 ears)and>48 months group(20 ears).The ABR latencies and interpeak latencies were compared between ASD children and age-matched TD children.② ASD children were graded by severity according to the Diagnostic and Statistical Manual of Mental Dis-orders(DSM-V),and the correlations between the ABR latencies and interpeak latencies in autistic children with normal hearing and the severity grading were studied.Results ① No statistically significant differences in ABR wave latencies and interpeak latencies were found in autistic children with normal hearing under 24 months of age compared to age-matched TD children(P>0.05).② Compared with children with TD,autistic children with nor-mal hearing at 25~36 months of age had significantly longer wave Ⅲ latencies and the interpeak latencies of Ⅰ-Ⅲ andⅠ-Ⅴ;the significantly longer wave Ⅲ,Ⅴ latencies,the interpeak latencies of Ⅰ-Ⅲ,Ⅲ-Ⅴ and Ⅰ-Ⅴ in autistic chil-dren with normal hearing at 37~48 months of age.Autistic children with normal hearing in the>48 months group had significantly longer wave Ⅴ latencies and interpeak latencies of Ⅲ-Ⅴ,Ⅰ-Ⅴ than age-matched TD children(P<0.05).③ The higher the ASD severity grading the longer the wave Ⅲ and V latencies and the longer interpeak latencies of Ⅰ-Ⅲ,Ⅲ-Ⅴ,and Ⅰ-Ⅴ(P<0.05).Conclusion Differences in the level of auditory brainstem pathway de-velopment emerged at 25 months of age,and autistic children with normal hearing had significantly lower levels of auditory brainstem development than age-matched TD children.There were correlations between the latencies and interpeak latencies of ABR in autistic children with normal hearing and the severity grading.
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BACKGROUND:Many clinical research observations have indicated a close association between rheumatoid arthritis and osteoporosis as well as bone mineral density(BMD).However,it remains unclear whether there is a causal genetic relationship between rheumatoid arthritis and the development of osteoporosis and alterations of BMD. OBJECTIVE:To assess the potential causal relationship between rheumatoid arthritis and osteoporosis as well as BMD using a two-sample Mendelian randomization approach,provide meaningful insights from a genetic perspective into the underlying mechanisms and offer a reference for early prevention of osteoporosis and improvement in the progression of the disease. METHODS:We conducted a study using data from publicly available genome-wide association studies databases to identify single nucleotide polymorphisms associated with rheumatoid arthritis as instrumental variables(P<5×10-8).The main outcomes of the study included osteoporosis and BMD at five different sites,including total body BMD,lumbar spine BMD,femoral neck BMD,heel BMD,and forearm BMD.The inverse variance-weighted method was used as the primary analysis method to evaluate causal effects.Weighted median,simple median,weighted mode and MR-Egger regression were used as supplementary analyses.Causal relationships between rheumatoid arthritis and the risk of osteoporosis and BMD were assessed using odds ratios(OR)and 95%confidence intervals(CI).Heterogeneity was assessed using Cochran's Q test and horizontal pleiotropy was evaluated using MR-Egger intercept tests. RESULTS AND CONCLUSION:The inverse variance-weighted analysis demonstrated a positive association between genetically predicted rheumatoid arthritis and osteoporosis(OR=1.123,95%CI:1.077-1.171;P=4.02×10-8).Heterogeneity test(P=0.388)indicated no significant heterogeneity among the single nucleotide polymorphisms.MR-Egger intercept(P=0.571)tests did not detect horizontal pleiotropy,and sensitivity analysis showed no evidence of bias in the study results.There was no causal relationship between rheumatoid arthritis and BMD at the five different sites.The total body BMD(OR=1.000,95%CI:0.988-1.012;P=0.925),lumbar spine BMD(OR=0.999,95%CI:0.982-1.016;P=0.937),femoral neck BMD(OR=1.001,95%CI:0.986-1.016;P=0.866),heel BMD(OR=0.996,95%CI:0.989-1.004;P=0.419),and forearm BMD(OR=1.063,95%CI:0.970-1.031;P=0.996)indicated no significant association.MR-Egger intercept analysis did not detect potential horizontal pleiotropy(total body BMD:P=0.253;lumbar spine BMD:P=0.638;femoral neck BMD:P=0.553;heel BMD:P=0.444;forearm BMD:P=0.079).Rheumatoid arthritis may contribute to the development of osteoporosis through the interaction between chronic inflammation and bone formation,resorption,and absorption.Additionally,the use of glucocorticoids and the presence of autoantibodies(such as anti-citrullinated protein antibody)in patients with rheumatoid arthritis showed associations with osteoporosis.Future research should focus on monitoring systemic inflammatory markers,standardized use of glucocorticoids,and regular screening for osteoporosis risk in patients with rheumatoid arthritis.
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BACKGROUND:Observational studies have suggested that statins may have a protective effect against osteoarthritis,including knee osteoarthritis and hip osteoarthritis.However,the association between statins and the risk of osteoarthritis remains unclear. OBJECTIVE:To investigate the association between statins and the risk of osteoarthritis through Mendelian randomization analysis using summary data from large-scale population-based genome-wide association studies(GWAS). METHODS:Firstly,single nucleotide polymorphism data related to statins were obtained from the latest 9th edition of the FinnGen database,while data of osteoarthritis,knee osteoarthritis and hip osteoarthritis were obtained from the IEU Open GWAS,UK Biobank,and ArcOGEN(Genetics of Osteoarthritis)databases,respectively.The inverse variance weighted method was used as the primary analysis approach to evaluate the causal effects.The weighted median method,simple median method,weighted mode-based method,and MR-Egger regression were used as supplementary analyses.The causal relationship between statins and the risk of osteoarthritis,knee osteoarthritis and hip osteoarthritis was assessed using odds ratios(OR)with 95%confidence intervals(CI).Sensitivity analyses were conducted to validate the reliability of the results,including the Cochran's Q test for heterogeneity and the MR-Egger-intercept test for horizontal pleiotropy,as well as leave-one-out analysis to identify potentially influential single nucleotide polymorphisms. RESULTS AND CONCLUSION:The inverse variance weighted analysis demonstrated a negative causal relationship between genetically predicted statins and the risk of osteoarthritis(OR=0.998,95%CI:0.996-0.999,P=0.01),knee osteoarthritis(OR=0.964,95%CI:0.940-0.989,P=0.005),and hip osteoarthritis(OR=0.928,95%CI:0.901-0.955,P=4.28×10-7).MR-Egger intercept analysis did not detect potential horizontal pleiotropy(osteoarthritis:P=0.658;knee osteoarthritis:P=0.600;hip osteoarthritis:P=0.141).The results of this study provide evidence that statins reduce the risks of osteoarthritis,knee osteoarthritis and hip osteoarthritis as described in observational studies.Further research is needed to explore the specific mechanisms of statin treatment for osteoarthritis.
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Objective To improve clinicians'understanding on Prevotella bloodstream infection(BSI),reduce the rate of misdiagnosis and missed diagnosis,and broaden the ideas of diagnosis and treatment.Methods Clinical data of patients with Prevotella BSI at a hospital affiliated to a medical school of Nanjing University from May 2013 to May 2023 were collected.Risk factors,sources of infection,strains of infection,clinical manifestations,laboratory test results,treatment,and outcomes of patients with Prevotella BSI were retrospectively analyzed.Results A to-tal of 23 patients diagnosed with Prevotella BSI were included in analysis,15(65.2%)were males and 8(34.8%)were females.Most patients had related predisposing factors before BSI,such as surgical procedures(n=11,47.8%),malignant tumors(n=10,43.5%),diabetes(n=9,39.1%),and indwelling urinary catheter(n=10,43.5%),etc.There were 9 types of infected bacteria,mainly Prevotella buccalis(n=6,26.1%),Prevotella bivia(n=5,21.7%)and Prevotella intermedia(n=4,17.4%).The main sources of infection were hepatobiliary system(n=6,26.1%),abdominal and thoracic cavities(n=4,17.4%),as well as urogenital tract(n=4,17.4%).All pa-tients showed symptoms of chills and fever,with significantly elevated blood inflammation indicators.Four cases(17.4%)developed septic shock,and 18 cases(78.3%)had a good prognosis after appropriate anti-infection treat-ment.Conclusion When atypical BSI caused by Prevotella is suspected,predisposing factors should be removed as soon as possible,blood should be actively collected and performed culture,rational use of antimicrobial agents based on antimicrobial susceptibility testing is beneficial for rapid control of infection and improvement of prognosis.
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【Objective】 To understand the prevalence of overweight/obesity among school-age children in Pudong New Area of Shanghai, and to explore the influence of gestational weight gain and pre-pregnancy body mass index (BMI) on weight status of school-age children. 【Methods】 From November to December 2020,a stratified cluster sampling method was adopted to select first-grade students from 13 primary schools in Pudong New Area of Shanghai.After matching with the birth monitoring database, 755 students with complete birth information were selected as the study subjects.The relevant information of mothers before and during pregnancy was retrospectively collected, and the effects of pregnancy weight gain combined with pre-pregnancy BMI on overweight/obesity in school-age children were analyzed. 【Results】 1) The prevalence rates of overweight and obesity of first-grade children were 15.89% and 18.41%, respectively.2) Maternal excessive weight gain during pregnancy (OR=1.678) and overweight/obesity before pregnancy (OR=2.315,2.412) were risk factors for overweight/obesity of the offspring at school age(P<0.05).3) For mothers who were underweight before pregnancy, excessive weight gain during pregnancy was associated with overweight/obesity in school-age children in their offspring (OR=7.436, 95%CI: 1.489 - 37.143,P<0.05).4) Excessive weight gain during pregnancy combined with overweight/obesity before pregnancy significantly increased the risk of overweight/obesity in offspring (OR=3.606, 95%CI: 2.030 - 6.405, P<0.05). Mothers who gained a moderate amount of weight during pregnancy and were emaciated before pregnancy had a significantly lower risk of overweight/obesity in their school-age children (OR=0.217, 95%CI: 0.049 - 0.967, P<0.05). 【Conclusion】 Excessive weight gain during pregnancy increases the risk of overweight/obesity in school-age children in their offspring, strengthening pregnancy health education and perinatal care to help pregnant women maintain appropriate weight gain during pregnancy may be an important and novel strategy to prevent childhood obesity.
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This paper discussed the clinical ideas and methods of treating diabetes by improving symptoms. Diabetes-related symptoms can affect the control of blood glucose and other metabolic indicators to varying degrees, and affect the quality of life of patients. In the clinical diagnosis and treatment of diabetes, “equal emphasis on both indicators” is suggested, meaning that quality of life indicators is as important as metabolic indicators. The patient's symptoms should be paied attention to, and the diagnosis and treatment should start from “symptom differentiation”, and emphasize the “key symptoms”. When there are many symptoms, it is advised to adopt the combined treatment mode of “syndrome cluster”, and take the principle of “treating both the root and accompanying symptoms in mild cases with multiple symptoms, and prescribing multiple formulas daily”. At the same time, the model of co-management of three disciplines of diabetes consisting of diabetes specialists, traditional Chinese medicine doctors, and health managers can help the management of diabetes symptoms.
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BACKGROUND@#Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer.@*METHODS@#Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38.@*RESULTS@#lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer.@*CONCLUSION@#Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.
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Humans , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic/genetics , MAP Kinase Signaling System , MicroRNAs/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , RNA, Long Noncoding/metabolism , Triple Negative Breast Neoplasms/pathologyABSTRACT
OBJECTIVE To investigate the effects of quercetin on mitochondrial energy metabolism function after myocardial ischemia. METHODS H9c2 cells were divided into blank group, model group, quercetin high-dose, medium-dose and low-dose groups (40, 20, 10 μmol/L), and positive control group (cyclosporine A, 1 μmol/L). Reactive oxygen species (ROS), mitochondrial membrane potential (MMP), openness of mitochondrial permeability transition pore (MPTP), adenosine triphosphate (ATP), malondialdehyde (MDA), lactate dehydrogenase (LDH) and creatine kinase (CK) were observed after cell hypoxia treatment. Rats were randomly assigned into sham operation group, model group, quercetin high-dose, medium-dose and low-dose groups (100, 50, 25 mg/kg), and positive control group (trimetazidine, 6.3 mg/kg), with 8 rats in each group. They were given relevant medicine intragastrically, once a day, for 7 consecutive days. After the last medication, myocardial ischemia model was induced by the ligation of the left anterior descending branch of the coronary artery. The contents of LDH, MDA, creatine kinase isoenzyme-MB (CK-MB), superoxide dismutase (SOD), complex Ⅰ, complex Ⅳ and ATP in serum were all determined. RESULTS Compared with the model group, ROS fluorescence intensity, openness of MPTP, the contents of CK, LDH and MDA were significantly decreased in quercetin low-dose, medium-dose and high-dose groups, and positive control group, while the contents of MMP and ATP were all increased significantly (P<0.01); the contents of CK-MB, LDH and MDA in serum were all decreased significantly in quercetin low-dose, medium-dose and high-dose groups, and positive control group, while the contents of SOD, complex Ⅰ, complex Ⅳ and ATP (except for positive control group) were increased significantly (P< 0.05 or P<0.01). CONCLUSIONS Quercetin can effectively reduce myocardial hypoxic injury, promote endogenous energy production and improve mitochondrial function after myocardial ischemia.
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Purpose This study aims to observe the hemodynamic state of the carotid artery in healthy volunteers and diabetes patients via ultrasound vector flow imaging(V-Flow),and to quantitatively analyze the characterization of wall shear stress(WSS)in different degrees of atherosclerosis carotid artery.Materials and Methods This was a cross-sectional study.Forty four diabetic patients diagnosed in Sichuan Provincial People's Hospital from April 2019 to June 2019 were retrospectively analyzed.Routine carotid ultrasound examination and V-Flow imaging were performed on 44 diabetic patients(88 vessels)and 15 controls(30 vessels).According to the results of carotid ultrasound examination,diabetic patients were divided into normal intima-media thickness(IMT)group,IMT thickening group and plaque group.The differences of WSS in different parts of carotid artery between diabetic patients and controls were observed,and the changes of WSS in different groups of diabetic patients were further compared and analyzed.Results In this study,the WSS(including WSSmax and WSSmean)of the bifurcation and middle segment of the common carotid artery in diabetic patients were significantly lower than those in the normal control group(P=0.001,P=0.003).WSS at the bifurcation of common carotid artery was significantly smaller than that at the middle segment of common carotid artery in both normal control group and diabetic group(P=0.001).WSS at the bifurcation of common carotid artery in diabetic patients was changed with the severity of atherosclerosis(P=0.018 and P=0.043),and was highest in the plaque group[WSSmax(2.58±0.69)Pa;WSSmean(0.86±0.25)Pa],followed by IMT thickening group[(2.37±0.69)Pa;(0.77±0.35)Pa].The WSS was lowest in the normal IMT group[(2.13±0.52)Pa;(0.69±0.20)Pa].There was no significant difference in WSS of the middle segment of common carotid artery among the three groups(P>0.05).Conclusion The WSS in the bifurcation and middle section of common carotid artery in diabetic patients is lower than that in controls,and it changed with the increase of atherosclerosis degree.Therefore,the V-Flow technique of ultrasonic vector flow imaging has a certain value in evaluating the progression of carotid atherosclerosis in diabetic patients.
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Objective To explore the spatial epidemiological characteristics of mortality and probability of premature death caused by chronic obstructive pulmonary disease (COPD) among residents in Pudong New Area of Shanghai from 2010 to 2020, and to provide reference for the formulation of chronic obstructive pulmonary disease prevention and control strategies according to local conditions. Methods The death data of chronic obstructive pulmonary disease were obtained from the local death surveillance system of Pudong New Area. Crude mortality, age-standardized mortality, and probability of premature death caused by COPD in each subdistricts and towns of Pudong New Area were calculated. The geographical information system (GIS) was used to plot the spatial distribution maps of chronic obstructive pulmonary disease death. The trend surface analysis and the spatial autocorrelation analysis were performed to analyze the spatial distribution of chronic obstructive pulmonary disease death. Results The crude mortality, age-standardized mortality and probability of premature death caused by COPD among residents in Pudong New Area between 2010 and 2020 were 58.40/100,000, 22.35/100,000, and 0.26%, respectively. The results of trend surface analysis showed that the crude mortality, age-standardized mortality and probability of premature death caused by COPD gradually increased from north to south. In the east-west direction, the crude mortality, age-standardized mortality, and probability of premature death showed an upward trend from west to east. The global autocorrelation analysis suggested that there existed a positive spatial autocorrelation for the crude mortality, age-standardized mortality, and probability of premature death. The local spatial autocorrelation analysis showed that the high-high clustering areas of COPD crude mortality, standardized mortality and premature mortality were all located in the rural areas of the southeast of Pudong New Area. Conclusion There are urban and rural differences in the mortality of chronic obstructive pulmonary disease among residents in Pudong New Area from 2010 to 2020. The residents living in rural southeast coast of Pudong New Area are more seriously affected by chronic obstructive pulmonary disease and should be paid more attention.
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@#Peri-implantitis and implant failure are common issues in the implant dentistry. The contaminated implant can be treated with mechanical, chemical and assisted methods for the formation of re-osseointegration. Re-osseointegration is achievable with valid bone regeneration strategies. The survival rate of implant into the site of previous failure is lower than that of the initial implant. For the hopeless and failed implant, it is necessary to remove the implant with corresponding technique.
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Objective: To investigate the effect of rigosertib (RGS) combined with classic chemotherapy drugs including 5-fluorouracil, oxaliplatin, and irinotecan in colorectal cancer. Methods: Explore the synergy effects of RGS and 5-fluorouracil (5-FU), oxaliplatin (OXA), and irinotecan (IRI) on colorectal cancer by subcutaneously transplanted tumor models of mice. The mice were randomly divided into control group, RGS group, 5-FU group, OXA group, IRI group, 5-FU+ RGS group, OXA+ RGS group and IRI+ RGS group. The synergy effects of RGS and OXA on KRAS mutant colorectal cancer cell lines in vitro was detected by CCK-8. Ki-67 immunohistochemistry and TdT-mediated dUTP nick-end labeling (TUNEL) staining were performed on the mouse tumor tissue sections, and the extracted tumor tissue was analyzed by western blot. The blood samples of mice after chemotherapy and RGS treatment were collected, blood routine and liver and kidney function analysis were conducted, and H&E staining on liver sections was performed to observe the side effects of chemotherapy and RGS. Results: The subcutaneously transplanted tumor models were established successfully in all groups. 55 days after administration, the fold change of tumor size of OXA+ RGS group was 37.019±8.634, which is significantly smaller than 77.571±15.387 of RGS group (P=0.029) and 92.500±13.279 of OXA group (P=0.008). Immunohistochemical staining showed that the Ki-67 index of tumor tissue in control group, OXA group, RGS group and OXA+ RGS group were (100.0±16.8)%, (35.6±11.3)%, (54.5±18.1)% and (15.4±3.9)%, respectively. The Ki-67 index of OXA+ RGS group was significantly lower than that in control group (P=0.014), but there was no significant difference compared to OXA group and RGS group (OXA: P=0.549; RGS: P=0.218). TUNEL fluorescence staining showed that the apoptotic level of OXA+ RGS group was 3.878±0.547, which was significantly higher than 1.515±0.442 of OXA group (P=0.005) and 1.966±0.261 of RGS group (P=0.008). Western blot showed that the expressions of apoptosis related proteins such as cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 8 in the tumor tissues of mice in the OXA+ RGS group were higher than those in control group, OXA group and RGS group. After the mice received RGS combined with chemotherapy drugs, there was no significant effect on liver and kidney function indexes, but the combined use of oxaliplatin and RGS significantly reduced the white blood cells [(0.385±0.215)×10(9)/L vs (5.598±0.605)×10(9)/L, P<0.001] and hemoglobin[(56.000±24.000)g/L vs (153.333±2.231)g/L, P=0.001] of the mice. RGS, chemotherapy combined with RGS and chemotherapy alone did not significantly increase the damage to liver cells. Conclusions: The combination of RGS and oxaliplatin has a stronger anti-tumor effect on KRAS mutant colorectal cancer. RGS single agent will not cause significant bone marrow suppression and hepatorenal injury in mice, but its side effects may increase correspondingly after combined with chemotherapy.
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Animals , Mice , Antineoplastic Combined Chemotherapy Protocols , Apoptosis Regulatory Proteins , Colorectal Neoplasms/genetics , Fluorouracil/pharmacology , Irinotecan/therapeutic use , Ki-67 Antigen , Oxaliplatin , Proto-Oncogene Proteins p21(ras)/therapeutic useABSTRACT
Objective: To evaluate the household secondary attack rates of the SARS-CoV-2 Delta variant and the associated factors. Methods: A COVID-19 outbreak caused by the Delta variant occurred in Nanjing in July 2021. A total of 235 cases with current addresses in Nanjing were reported from 171 households. The subjects in this study were selected from household close contact(s) of infected cases. The information on household index cases and their contacts were collected, and the household secondary attack rate (HSAR) and the risk factors were analyzed by the multi-factor logistic regression model. Results: A total of 234 cases of household close contacts and 64 household secondary cases were reported from 103 households, and the HSAR was 27.4% (64/234, 95%CI:22.0% to 33.4%). The proportions of household size for 2 to 3, 4 to 5, and 6 to 9 were 64.1% (66), 26.2% (27) and 9.7% (10), respectively. A total of 35 cases of household cluster outbreaks were reported (35/103, 34.0%). The number of the first case in the household (FCH) was 103 and males accounted for 27.2% (28 cases), with the median age (Q1, Q3) of 49 (9, 56). The number of household close contacts was 234 and males accounted for 59.0% (138 cases), with the median age (Q1, Q3) of 42 (20, 55) and the median exposure period (Q1, Q3) of 3 (1, 3) days. The multi-factor logistic regression model showed that the higher HSAR was observed in the FCH with the features of airport staff (OR=2.913, 95%CI:1.469-5.774), detection from home quarantine screening (OR=6.795, 95%CI:1.761-26.219) and detection from mass screening (OR=4.239, 95%CI:1.098-16.368). Meanwhile, higher HSAR was observed in cases with longer household exposure (OR=1.221, 95%CI:1.040-1.432), non-vaccination (OR=2.963, 95%CI:1.288-6.813) and incomplete vaccinations (OR=2.842, 95%CI:0.925-8.731). Conclusion: The generation interval of the Delta variant is shortened, and the ability of transmission within the household is enhanced. In the outbreak in Nanjing, the associated factors of HSAR are occupation, detection route, vaccination and exposure period.
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Male , Humans , SARS-CoV-2 , COVID-19/epidemiology , Incidence , Family CharacteristicsABSTRACT
ObjectiveTo investigate the epidemiological traits and potential years of life lost associated with lung cancer mortality among inhabitants of Shanghai's Pudong New Area from 1995 to 2021, in order to serve as a reference for developing intervention approaches. MethodsThe death surveillance system was used to gather statistics on lung cancer deaths. Crude mortality rate (CMR), standardized mortality rate (SMR), potential years of life lost (PYLL), average years of life lost (AYLL), annual percent change (APC) of the lung cancer deaths were analyzed. The impact of age-structural and non-age-structural factors on changes in lung cancer mortality was quantified using difference decomposition. ResultsThe CMR and SMR of lung cancer among residents in Pudong New Area between 1995 and 2021 were 58.21/105 and 26.75/105, respectively. The CMR of lung cancer increased over the years (APC=1.91%, 95%CI=1.60%‒2.30%; Z=11.487, P<0.001), and the SMR of lung cancer declined over the years (APC=-1.50%, 95%CI=-1.80%‒-1.20%; Z=-9.006, P<0.001). Age structure factors and gender factors contributed to the increase of lung cancer mortality, while non-population age structure factors overall appeared to play a protective role which might be related to the improvements in factors such as tobacco control and environmental management. The PYLL of lung cancer was 160 296 person years, the PYLL rate was 2.24‰, and the AYLL was 3.86 years per person. ConclusionAge structure factors are a significant contributor to the disease burden and result in the increase in the crude lung cancer mortality rate of Pudong residents of shanghai. Comprehensive monitoring, preventive, and control methods should be implemented.
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Objective:To investigate short-term safety, efficacy and the learning curve of this self-developed novel transcatheter valve repair system (Neonova?) in patients with mitral regurgitation, and explore the role of perioperative echocardiography.Methods:Ten patients who visited the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from June 2021 to March 2022 and met the inclusive criteria were prospectively enrolled. All the patients were at high risk of surgery with moderate to severe or severe mitral regurgitation (MR). Clamps of Neonova? were implanted under guidance of transesophageal echocardiography and digital subtraction angiography. Clinical outcomes, echocardiography indexes and learning curves of this technique were evaluated immediately after intervention, 7 d, 1 month and 3 months post-intervention.Results:The technical success rate was 100% with MR relieved in all patients immediately after intervention. The device and procedural success rates were both 90.0% with 1 patient received surgical replacement at 37 days post-intervention while the others′ reduced to mild (8/9) and moderate (1/9) MR. New York Heart Association class and the Kansas City Cardiomyopathy Questionnaire improved significantly (all P<0.001). Mean mitral valve pressure gradient didn′t increase significantly after intervention when compared with that before intervention( P=0.324), and no mitral stenosis was observed. Left ventricular end-diastolic diameter decreased significantly ( P=0.008) during follow up.Procedure duration ranged from 60 to 300 (175.8±75.2)minutes. The simple linear regression model between procedure volume and duration showed that procedure duration decreased significantly with the increase of procedure volume ( F=15.857, P=0.004). Conclusions:Neonova? implantation can improve MR severity and clinical symptoms safely and effectively. Transthoracic echocardiography and transesophageal echocardiography are essential for perioperative management of transcatheter mitral valve repair.
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Objective@#Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder with significant gender differences. The sexual dimorphism of ADHD may be associated with estrogen acting through estrogen receptors (ESR). This study investigates the impact of ESR gene polymorphism and its interactions with neurodevelopmental genes on ADHD susceptibility. @*Methods@#The study compared genotyping data of single nucleotide polymorphisms in ESR1 and ESR2 in 1,035 ADHD cases and 962 controls. The gene-gene interactions between ESR genes and three neurodevelopmental genes (brain-derived neurotrophic factor [BDNF], synaptosomal-associated protein of 25 kDa gene [SNAP25], and cadherin-13 [CDH13]) in ADHD were investigated using generalized multifactor dimensionality reduction and verified by logistic regression analysis. @*Results@#The G allele of rs960070/ESR2 (empirical p=0.0076) and the A allele of rs8017441/ESR2 (empirical p=0.0426) were found significantly higher in ADHD cases than in the controls but not in male or female subgroups. Though no difference was found in all subjects or females, the A allele of rs9340817/ESR1 (empirical p=0.0344) was found significantly higher in ADHD cases than controls in males. We also found genetic interaction models between ESR2 gene, neurodevelopmental genes and ADHD susceptibility in males (ESR2 rs960070/BDNF rs6265/BDNF rs2049046/SNAP25 rs362987/CDH13 rs6565113) and females (ESR2 rs960070/BDNF rs6265/BDNF rs2049046) separately, though it was negative in overall subjects. @*Conclusion@#The ESR gene polymorphism associates with ADHD among Chinese Han children, with interactions between ESR genes and neurodevelopmental genes potentially influencing the susceptibility of ADHD.
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Fabry disease is an X-linked lysosomal storage disease, and its pathogenesis is the deficient of α-galactosidase A (α-Gal A) activity caused by GLA mutation, which leads to accumulation of the glycosphingolipid globotriaosylceramide (Gb-3) and other glycosphingolipids in the lysosome of cells, resulting in the dysfunction of relevant tissues and organs. We report the clinical characteristics of a case of Fabry disease with dermatomyositis. The patient, a 61-year-old male, presented with intermittent amaurosis, limb weakness and dyspnea on exertion. Based on the low α-Gal A activity and positive anti-myositis antibodies, diagnosis of Fabry disease with dermatomyositis were confirmed. We reviewed the relevant literature and found that co-existence of Fabry disease and autoimmune diseases was very rare, but it is not rare for patients with Fabry disease to have some autoimmune antibody positive, suggesting that Fabry disease and autoimmune diseases may be related in pathogenesis.