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INTRODUCTION: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. METHODS: This study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures. RESULTS: A total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q<0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are associated with cognitive function and mood regulation. CONCLUSION: The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.
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INTRODUCTION: Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations in a large Chinese general population to inform future Chinese ESCC screening guidelines. METHODS: We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models. RESULTS: We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women. DISCUSSION: This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.
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Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Biópsia , China/epidemiologia , Esofagoscopia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The diabetic foot is a common cause of disability and death, and comorbid foot infections usually lead to prolonged hospitalization, high healthcare costs, and a significant increase in amputation rates. And most diabetic foot trauma is complicated by lower extremity arteriopathy, which becomes an independent risk factor for major amputation in diabetic foot patients. AIM: To establish the efficacy and safety of endovascular revascularization (ER) combined with vacuum-assisted closure (VAC) for the treatment of diabetic foot. METHODS: Clinical data were collected from 40 patients with diabetic foot admitted to the Second Affiliated Hospital of Soochow University from April 2018 to April 2022. Diabetic foot lesions were graded according to Wagner's classification, and blood flow to the lower extremity was evaluated using the ankle-brachial index test and computerized tomography angiography of the lower extremity arteries. Continuous subcutaneous insulin infusion pumps were used to achieve glycemic control. Lower limb revascularization was facilitated by percutaneous tran-sluminal balloon angioplasty (BA) or stenting. Wounds were cleaned by nibbling debridement. Wound granulation tissue growth was induced by VAC, and wound repair was performed by skin grafting or skin flap transplantation. RESULTS: Of the 35 cases treated with lower limb revascularization, 34 were successful with a revascularization success rate of 97%. Of these, 6 cases underwent stenting after BA of the superficial femoral artery, and 1 received popliteal artery stent implantation. In the 25 cases treated with infrapopliteal artery revascularization, 39 arteries were reconstructed, 7 of which were treated by drug-coated BA and the remaining 32 with plain old BA. VAC was performed in 32 wounds. Twenty-four cases of skin grafting and 2 cases of skin flap transplantation were performed. Two patients underwent major amputations, whereas 17 had minor amputations, accounting for a success limb salvage rate of 95%. CONCLUSION: ER in combination with VAC is a safe and effective treatment for diabetic foot that can significantly improve limb salvage rates. The use of VAC after ER simplifies and facilitates wound repair.
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Sulfonylaniline motif plays an important role in pharmaceutical sciences. Developed methods towards this structure are typically lack of good modifiability and stability. In this study, visible-light-mediated sulfonylation of aniline using sulfonyl fluoride as a modifiable and stable sulfonylation reagent is described. A variety of substituted sulfonylanilines were synthesized under mild reaction conditions with moderate to good efficiency. The example of late-stage sulfonylation highlighted the advantage of using sulfonyl fluoride as a sulfonylation reagent. In addition, the crucial influence of counterions on the photocatalyst observed in this system would inspire further research on the photochemistry of sulfonyl fluoride.
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Ranibizumab is a monoclonal antibody fragment targeted against vascular endothelial growth factor (VEGF) A isoform (VEGF-A). This study aimed to report a case of esophageal ulcer that developed soon after intravitreal ranibizumab injection in a patient with age-related macular degeneration (AMD). A 53-year-old male patient diagnosed with AMD received ranibizumab through intravitreal injection in the left eye. Mild dysphagia occurred 3 days after receiving intravitreal ranibizumab injection for the second time. The dysphagia exacerbated remarkably and was accompanied by hemoptysis 1 day after receiving ranibizumab for the third time. Severe dysphagia accompanied by intense retrosternal pain and pant emerged after injecting ranibizumab for the fourth time. An esophageal ulcer was observed through ultrasound gastroscopy, covered with fibrinous tissue, and surrounded by flushing and congestive mucosae. The patient received proton pump inhibitor (PPI) therapy combined with traditional Chinese medicine (TCM) after discontinuation of ranibizumab. The dysphagia and retrosternal pain were gradually relieved after treatment. Afterwards, the esophageal ulcer has not relapsed since permanent discontinuation of ranibizumab. To our best knowledge, this was the first case of esophageal ulcer related to intravitreal ranibizumab injection. Our study indicated that VEGF-A played a potential role in the development of esophageal ulceration.
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The aim of this study was to investigate the clinical characteristics and prognosis of patients hospitalized with heart failure with preserved ejection fraction (HFpEF) and low N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Seven hundred ninety consecutive patients hospitalized with HFpEF from 2006 to 2017 were enrolled. Clinical characteristics and outcomes were compared between low NT-proBNP group (<300 ng/L) and elevated NT-proBNP group (≥300 ng/L). 108 HFpEF patients (13.7%) presented with low NT-proBNP levels. Age, body mass index, atrial fibrillation, New York Heart Association functional class, and albumin were independent predictors of low NT-proBNP levels in HFpEF patients. During the median follow-up duration of 1103 days, 11 patients (10.2%) in low NT-proBNP group suffered from primary endpoint event. Elevated NT-proBNP group had a higher risk of all-cause death or heart transplantation than low NT-proBNP group (adjusted HR [95%CI]: 2.36 [1.24,4.49], Pâ =â .009). Stratified analyses showed that the association between NT-proBNP (elevated NT-proBNP group vs low NT-proBNP group) and risk of all-cause death or heart transplantation was stronger in non-atrial fibrillation patients than in atrial fibrillation patients (P value for interactionâ =â .025). Furthermore, the associations between NT-proBNP and risk of all-cause death or heart transplantation were stronger in younger and male patients than in older and female patients. However, both subgroups only reached borderline significant (P values for interactionâ =â .062 and .084, respectively). Our findings suggest that low NT-proBNP levels were common in patients hospitalized with HFpEF. Patients with HFpEF and low NT-proBNP levels had a better prognosis than those with elevated NT-proBNP levels, particularly in younger, male, and non-atrial fibrillation patients.
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Fibrilação Atrial , Insuficiência Cardíaca , Humanos , Masculino , Feminino , Idoso , Peptídeo Natriurético Encefálico , Volume Sistólico , Prognóstico , Fragmentos de Peptídeos , BiomarcadoresRESUMO
PURPOSE: There are no global screening recommendations for esophageal squamous cell carcinoma (ESCC). Endoscopic screening has been investigated in areas of high incidence in China since the 1970s. This study aimed to evaluate whether an endoscopic screening and intervention program could reduce mortality caused by ESCC. METHODS: Residents age 40 to 69 years were recruited from communities with high rates of ESCC. Fourteen villages were selected as the intervention communities. Ten villages not geographically adjacent to intervention villages were selected for comparison. Participants in the intervention group were screened once by endoscopy with Lugol's iodine staining, and those with dysplasia or occult cancer were treated. All intervention participants and a sample consisting of one tenth of the control group completed questionnaires. We compared cumulative ESCC incidence and mortality between the two groups. RESULTS: Three thousand three hundred nineteen volunteers (48.62%) from an eligible population of 6,827 were screened in the intervention group. Seven hundred ninety-seven volunteers from an eligible population of 6,200 in the control group were interviewed. Six hundred fifty-two incident and 542 fatal ESCCs were identified during the 10-year follow-up. A reduction in cumulative mortality in the intervention group versus the control group was apparent (3.35% v 5.05%, respectively; P < .001). Furthermore, the intervention group had a significantly lower cumulative incidence of ESCC versus the control group (4.17% v 5.92%, respectively; P < .001). CONCLUSION: We showed that endoscopic screening and intervention significantly reduced mortality caused by esophageal cancer. Detection and treatment of preneoplastic lesions also led to a reduction in the incidence of this highly fatal cancer.
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Povo Asiático/estatística & dados numéricos , Detecção Precoce de Câncer/métodos , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Esofagoscopia , Programas de Rastreamento/métodos , Adulto , Idoso , China/epidemiologia , Neoplasias Esofágicas/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Características de Residência , Fatores de TempoRESUMO
BACKGROUND: Esophageal cancer is one of the most frequently occurring malignancies and the seventh leading cause of cancer-related deaths in the world. The esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer worldwide. MATERIALS AND METHODS: Our goal in this study was to detect phospholipase A2 Group IIA (PLA2G2A) and cyclooxygenase-2 (COX-2) immuno-expression in ESCC in a high- risk population in China. RESULTS: Positive expression of PLA2G2A protein was observed in 57.2% (166/290) of the cases, while COX-2 was found in 257 of 290 samples (88.6%), both PLA2G2A and COX-2 being expressed in 153 cases (52.8%), with a significant agreement (Kappa=0.091, p=0.031).Overexpression of PLA2G2A was significantly correlated with the depth of invasion (p=0.001). Co-expression of PLA2G2A and COX-2 not only significantly correlated with the depth of invasion (p=0.004) but also with TNM stage (p=0.04). CONCLUSIONS: Our results showed that in patients with ESCC, PLA2G2A overexpression and PLA2G2A co-expression with COX-2 is significantly correlated with advanced stage. The biological role and pathophysiologic regulation of PLA2G2A and COX-2 overexpression in ESCC deserve further investigation.
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Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Ciclo-Oxigenase 2/metabolismo , Neoplasias Esofágicas/enzimologia , Neoplasias Esofágicas/patologia , Fosfolipases A2 do Grupo II/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Biópsia por Agulha , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The prostaglandin-endoperoxide synthase 2 (PTGS2) and phospholipase A2 group IIA (PLA2G2A) genes encode enzymes that are involved in arachidonic acid and prostaglandin biosynthesis. Dysregulation of both genes is associated with inflammation and carcinogenesis, including esophageal squamous cell carcinoma (ESCC). We therefore hypothesized that there is an association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to ESCC. METHODS: We performed a gene-wide tag SNP-based association study to examine the association of SNPs in PTGS2 and PLA2G2A with ESCC in 269 patients and 269 healthy controls from Taihangshan Mountain, Henan and Hebei Provinces, the rural area of China which has the highest incidence of esophageal cancer in the world. Thirteen tag SNPs in PLA2G2A and 4 functional SNPs in PTGS2 were selected and genotyped using a high-throughput Mass Array genotyping platform. RESULTS: We found a modest increased risk of ESCC in subjects with the PTGS2 rs12042763 AA genotype (OR=1.23; 95% CI, 1.00- 3.04) compared with genotype GG. For PLA2G2A, a decreased risk of ESCC was observed in subjects with the rs11677 CT (OR=0.51, 95%CI, 0.29-0.85) or TT genotype (OR=0.51, 95%CI, 0.17-0.96) or the T carriers (CT+TT) (OR=0.52, 95%CI, 0.31-0.85) when compared with the CC genotype. Also for PLA2G2A, rs2236771 C allele carriers were more frequent in the control group (P=0.02). Subjects with the GC (OR=0.55, 95%CI, 0.33-0.93) or CC genotype (OR=0.38, 95% CI, 0.16-0.94) or the C carriers (GC+CC) (OR=0.52, 95%CI, 0.32- 0.85) showed a negative association with ESCC susceptibility. CONCLUSIONS: Our results suggest that PTGS2 and PLA2G2A gene polymorphisms may modify the risk of ESCC development.
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Carcinoma de Células Escamosas/genética , Ciclo-Oxigenase 2/genética , Neoplasias Esofágicas/genética , Fosfolipases A2 do Grupo II/genética , Sequência de Bases , Estudos de Casos e Controles , Carcinoma de Células Escamosas do Esôfago , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco , Análise de Sequência de DNARESUMO
AIM: To explore the DNA image cytometry (DNA-ICM) technique as a primary screening method for esophageal squamous precancerous lesions. METHODS: This study was designed as a population-based screening study. A total of 582 local residents aged 40 years-69 years were recruited from Linzhou in Henan and Feicheng in Shandong. However, only 452 subjects had results of liquid-based cytology, DNA-ICM and pathology. The sensitivity and specificity of DNA-ICM were calculated and compared with liquid-based cytology in moderate dysplasia or worse. RESULTS: Sensitivities of DNA-ICM ranging from at least 1 to 4 aneuploid cells were 90.91%, 86.36%, 79.55% and 77.27%, respectively, which were better than that of liquid-based cytology (75%). Specificities of DNA-ICM were 70.83%, 84.07%, 92.65% and 96.81%, but the specificity of liquid-based cytology was 91.91%. The sensitivity and specificity of a combination of liquid-based cytology and DNA-ICM were 84.09% and 85.78%, respectively. CONCLUSION: It is possible to use DNA-ICM technique as a primary screening method for esophageal squamous precancerous lesions.
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DNA , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Citometria por Imagem/métodos , Programas de Rastreamento/métodos , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/genética , Adulto , Idoso , China , Citodiagnóstico/métodos , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Curva ROC , Sensibilidade e EspecificidadeRESUMO
Formic acid and formaldehyde are the important and ubiquitous chemical constituents in the atmosphere. Precipitation in Guiyang, the capital city of Guizhou province, was analyzed with ICS-90 ion chromatography for their concentration changes in a year. The volume mean weight average concentration (VMWA) is (13.27 +/- 25.92) micromol/L and (7.89 +/- 8.92) micromol/L for formic acid and formaldehyde, respectively. Both species demonstrated higher concentration during winter-half-year than the summer-half-year. Day-time concentration is higher than the night-time, the diurnal variations for both chemical constituents indicate the sources from human activities and photochemical reactions. Regression analysis of concentration vs precipitation volume and deposition amount vs precipitation volume reveals that dilution and scavenging of precipitation in the below-cloud process are responsible for the changes of the concentrations. The significant correlation between formic acid and formaldehyde suggests similar sources or reaction relationship. The known aqueous oxidation of formaldehyde, however, can not be used to explain the link of the two compounds, and thus should not be the major source of formic acid in Guiyang, Instead, photochemical reactions of unsaturated hydrocarbons (natural or anthropological) were the major sources for formic acid and formaldehyde.
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Poluentes Atmosféricos/análise , Formaldeído/análise , Formiatos/análise , Chuva/química , Poluentes Atmosféricos/química , China , Formaldeído/química , Formiatos/química , Cinética , Modelos Químicos , Estações do AnoRESUMO
Esophageal cancer is a leading cause of cancer death, especially in developing countries. In high-risk regions, squamous cell carcinoma is the most common type of esophageal cancer, and its etiology remains poorly understood. The purpose of this study was to evaluate the association between human papillomavirus (HPV) infection and esophageal squamous cell carcinoma (ESCC) and related precursor lesions in a high-risk area of China. We conducted a cross-sectional study among adult inhabitants of Linxian, China. All subjects were interviewed about potential risk factors, had the length of their esophagus sampled by a balloon cytology examination and underwent endoscopy with mucosal iodine staining and biopsy of all unstained lesions. A multivalent HPV hybridization probe, Digene Hybrid Capture II (Gaithersburg, MD), which recognizes high-risk types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, was used to determine the HPV infection status of the cytologic specimens, and the endoscopic biopsies were used to classify each subject's esophageal disease. 740 subjects completed the cytologic and endoscopic exams, and 702 had adequate cytologic and biopsy specimens. Using a cutpoint of > or =3.0 pg/ml of HPV DNA to define a positive test, HPV positivity was identified in 13% (61/475) of subjects without squamous dysplasia, 8% (8/102) with mild dysplasia, 7% (6/83) with moderate dysplasia, 16% (6/38) with severe dysplasia and zero (0/4) with invasive ESCC. Changing the cutpoint defining a positive test did not change the association of HPV infection and dysplasia grade. In this high-risk population, infection of esophageal cells with high-risk HPV types occurs in 13% of asymptomatic adults with no evidence of squamous dysplasia and a similar proportion of individuals with mild, moderate or severe dysplasia. This suggests that HPV infection is not a major risk factor for ESCC in this high-risk Chinese population. Further studies are warranted to determine if infection with this agent is associated with neoplastic progression in a subset of cases.