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Objective: To explore the latest clinical characteristics and development trends of posterior malleolus fracture. Methods: Clinical information of inpatients with posterior malleolus fracture in Shanghai Tongji Hospital and Karamay Central Hospital from January 2014 to December 2022 were reviewed and collected. The imaging data of patients were acquired using the Picture Archiving and Communication Systems. A statistical analysis was performed as to gender, current age, year of admission, injury mechanism, fracture type, and posterior malleolus fracture classification. Moreover, a comparative analysis was conducted on the injury mechanisms and morphological differences of posterior malleolus fracture at different periods, regions, and age groups. Results: A total of 472 patients (210 patients from Shanghai Tongji Hospital and 262 patients from Karamay Central Hospital) with posterior malleolus fracture with a mean age of (48.7±15.6) years were included in this study. The peak of posterior malleolus fracture occurs in the age group of 50-59 years. The injury mechanisms mainly involve low-energy fall and sprain (411 cases, 87.1%), followed by traffic accidents (52 cases, 11.0%), and fall injury from height (9 cases, 1.9%). The number of cases according to different fracture types showed the following descending order: trimalleolar fracture-supination extorsion (335 cases, 71.0%), bimalleolar fracture (60 cases, 12.7%), trimalleolar fracture-pronation extorsion (43 cases, 9.1%), posterior malleolus+tibial shaft fracture (19 cases, 4.0%), simple posterior malleolus fracture (15 cases, 3.2%). The numbers of cases corresponding to the Haraguchi â , â ¡ and â ¢ type of posterior malleolus fractures was 369 (78.2%), 49 (10.4%), and 54 (11.4%), respectively. The Tongji â ¡A type represented the highest number of cases (249 cases, 52.8%), followed by the â ¡B type (120 cases, 25.4%), â type (54 cases, 11.4%), â ¢B type (36 cases, 7.6%), and â ¢A type (13 cases, 2.8%). However, no obvious statistical difference was observed in the injury mechanism, Haraguchi classification, and Tongji classification of posterior malleolus fractures among different years and regions from the year of 2014 to 2022 (all P>0.05). Conclusions: The injury mechanism of posterior malleolus fracture mainly involves low-energy fall and sprain cases. The trimalleolar fracture-supination extorsion, Haraguchi â type and Tongji â ¡A type of posterior malleolus fracture are predilection fracture types, and all present an obvious incidence peak in the age group of 50-59 years. There has been no significant change in the development trend of clinical characteristics of posterior malleolus fractures in recent years.
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Fraturas do Tornozelo , Traumatismos do Tornozelo , Entorses e Distensões , Adulto , Humanos , Pessoa de Meia-Idade , Fixação Interna de Fraturas , China/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objective: To explore the genotype-phenotype relationship of Wilson's disease (WD) and further study the mutation spectrum in the ATP7B gene. Methods: The clinical data and genetic test results of 115 cases with WD diagnosed in the First Affiliated Hospital of Zhengzhou University from 2015 to 2022 were retrospectively analyzed. The rank sum test was used for quantitative data comparison, and χ(2) test was used for count data comparison. Multivariate logistic regression was used to analyze the relationship between patients' genotype and phenotype. Results: The onset of liver manifestations (hepatic type) accounted for 60.9%, neurological symptoms (cerebral type) for 13.0%, and mixed hepato-cerebral symptoms for 26.1%. Presymptomatic individuals (hepatic types) accounted for 62.9%. Next-generation sequencing- diagnosed WD cases accounted for 87.8%. Combined multiplex ligation-dependent probe amplification assay-diagnosed WD cases accounted for 89.6%. A single case with a detected pathogenic locus accounted for 10.4%. The diagnostic rate of WD by genetic testing combined with clinical data was 100%. A total of 76 ATP7B mutations were detected, and the top three mutation frequencies were c.2333G>T (p.Arg778Leu) (30.7%), c.2975C>T (p.Pro992Leu) (7.3%), and c.2621C>T (p.Ala874Val) (6.4%). The mutations were mainly distributed in exons 8, 11-13, and 15-18, accounting for more than 90% of the total mutations. Eight new mutations were found, including c.3724G>A (p.Glu1242Lys), c.3703G>C (p.Gly1235Arg), c.3593T>C (p.Val1198Ala), c.2494A>C (p.Lys832Gln), c.1517T>A (p.Ile506Lys), c.484G>T (p.Glu162Ter), c.1870-49A>G, and the missing of exons 10-21. Liver histopathology showed cellular edema, degeneration, inflammation, and necrosis, as well as a 42.8% copper staining positive rate. Genotype-phenotype analysis showed that the p.Arg778Leu mutation had higher alanine aminotransferase (ALT) levels than those carrying other mutations (P=0.024), while the homozygous mutation of p.Arg778Leu was associated with cerebral-type patients (P=0.027). Conclusion: Genetic testing plays an important role in the diagnosis of WD. p.Arg778Leu is the first high-frequency mutation in the Chinese population, and patients carrying it have higher ALT levels. The p.Arg778Leu homozygous mutation is prone to causing cerebral-type WD. This study expands the ATP7B gene mutation spectrum.
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ATPases Transportadoras de Cobre , Genótipo , Degeneração Hepatolenticular , Mutação , Fenótipo , Humanos , Degeneração Hepatolenticular/genética , Degeneração Hepatolenticular/diagnóstico , ATPases Transportadoras de Cobre/genética , Estudos Retrospectivos , Feminino , Masculino , Proteínas de Transporte de Cátions/genética , Estudos de Associação Genética , Adulto , Adenosina Trifosfatases/genética , Adulto Jovem , Adolescente , Criança , Testes Genéticos , Pessoa de Meia-Idade , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Objective: To investigate the prevalence and associated risk of cardiovascular event of resistant hypertension in treated outpatients. Methods: This study was a nationwide multi-center prospective cohort study. The participants were treated outpatients enrolled in the China Nationwide Ambulatory and Home Blood Pressure Registry study of 42 hospitals in 19 provinces across the country from August 2009 to October 2017. Apparent resistant hypertension was defined as uncontrolled office blood pressure (≥140/90 mmHg, 1 mmHg=0.133 kPa) in spite of the use of three antihypertensive drugs or controlled office blood pressure (<140/90 mmHg) with four antihypertensive drugs or more. Subjects diagnosed with uncontrolled office blood pressure were further subdivided as pseudo-resistant hypertension and true resistant hypertension based on 24 h ambulatory blood pressure monitoring. The primary endpoint was fatal and non-fatal cardiovascular and cerebrovascular events, which was a composite endpoint consisting of cardiovascular and cerebrovascular death, ischemic and hemorrhagic stroke, myocardial infarction, coronary artery revascularization, unstable angina, heart failure, and coronary artery stenosis≥50% confirmed by coronary angiography. Secondary outcomes included fatal and non-fatal stroke or cardiac events. Patients with controlled office blood pressure after taking only 1 or 2 antihypertensive drugs were included as control. Kaplan-Meier survival curves, log-rank test, and Cox proportional risk model were used to evaluate the risk of apparent refractory hypertension in relation to cardiovascular and cerebrovascular prognosis. Results: A total of 2 782 treated hypertensive patients, aged (58.1±12.3) years were enrolled, including 1 403 (50.4%) men. The prevalence of apparent and true resistant hypertension was 15.1% (420/2 782) and 10.5% (293/2 782), respectively. Among patients with apparent resistant hypertension, during a median of 5 years follow-up, the cumulative incidence rate was 28.2, 11.2 and 19.1 per 1 000 person-years for fatal and non-fatal cardiovascular events (n=58), stroke (n=24) and cardiac events (n=40), respectively. The Kaplan-Meier curve and log-rank test showed that those patients with true resistant hypertension, had the highest cumulative incidence rate of fatal and non-fatal cardiovascular events, stroke, and cardiac events. Multivariable Cox regression analyses showed that true resistant hypertension was associated with a significantly higher risk of fatal and non-fatal cardiovascular events (HR=1.73, 95%CI 1.17-2.56, P=0.006) and stroke (HR=2.81, 95%CI 1.53-5.17, P=0.001). Conclusion: Resistant hypertension, especially true resistant hypertension, is associated with a higher risk of fatal and non-fatal cardiac and cerebrovascular events.
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Anti-Hipertensivos , Hipertensão , Pacientes Ambulatoriais , Humanos , Hipertensão/epidemiologia , Hipertensão/complicações , Estudos Prospectivos , Anti-Hipertensivos/uso terapêutico , Prognóstico , Fatores de Risco , Pressão Sanguínea , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , PrevalênciaRESUMO
The list of occupational diseases reflecting the latest advances in the identification and recognition of occupational diseases, and providing guidance on the protection of workers' health rights and interests and the prevention, recording, notification and compensation of related occupational diseases. Diagnostic criteria for occupational diseases are an important basis for making diagnoses attributable to occupational diseases, and provide a theoretical basis for health monitoring of occupational groups and occupational hygiene supervision. This thesis starts with the definition of the occupational disease elaborates in detail the development history of list of occupational diseases in International Labour Organization (ILO) , compares the list of occupational diseases in China (2013 version) with the list of occupational diseases in international (2010 version) , and then introduces in detail the latest diagnostic standards of the major occupational diseases. And finally, it puts forward relevant suggestions on the list and diagnostic level of China's occupational diseases, so as to provide certain insights for the further improvement of the list and diagnostic standards of occupational diseases.
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Doenças Profissionais , Humanos , Doenças Profissionais/diagnóstico , China , Saúde OcupacionalRESUMO
We report a search for cosmic-ray boosted dark matter with protons using the 0.37 megaton×years data collected at Super-Kamiokande experiment during the 1996-2018 period (SKI-IV phase). We searched for an excess of proton recoils above the atmospheric neutrino background from the vicinity of the Galactic Center. No such excess is observed, and limits are calculated for two reference models of dark matter with either a constant interaction cross section or through a scalar mediator. This is the first experimental search for boosted dark matter with hadrons using directional information. The results present the most stringent limits on cosmic-ray boosted dark matter and exclude the dark matter-nucleon elastic scattering cross section between 10^{-33}cm^{2} and 10^{-27}cm^{2} for dark matter mass from 1 MeV/c^{2} to 300 MeV/c^{2}.
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This corrects the article DOI: 10.1103/PhysRevLett.130.031802.
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AIM: To reveal the prognostic value of the postoperative and dynamic albumin-to-alkaline phosphatase ratio (AAPR) in hepatocellular carcinoma (HCC) patients undergoing trans-catheter chemoembolisation (TACE). MATERIALS AND METHODS: In total, 545 HCC patients undergoing initial TACE were enrolled into the study. The receiver operating characteristic (ROC) curve was plotted to determine the best cut-off for AAPR. Univariate and multivariate Cox regression analyses were used to confirm the independent prognostic effect of AAPR on overall survival (OS). The predictive performance of AAPR was assessed by ROC curves, concordance index (C-index), and Akaike information criterion (AIC), and was compared to existing liver function assessment systems. RESULTS: The optimal cut-off value for the AAPR was 0.26. Elevated AAPR (>0.26) was associated with a low risk of death after adjustment whether before (HR: 0.53; 95% CI: 0.4-0.69) or after (HR: 0.64; 95% CI: 0.43-0.95) TACE treatment. The combined pre- and postoperative AAPR showed much better performance in ROC curve (1-, 3-, and 5-year AUCs: 0.69, 0.71, 0.69), C-index (0.65; 95% CI: 0.59-0.72) and AIC analyses than pre-AAPR and post-AAPR alone or liver function assessment systems. CONCLUSION: This study demonstrated both preoperative and postoperative AAPR were independent prognostic factors for HCC patients undergoing TACE. In addition, the combined pre- and post-AAPR showed better predictive performance than pre-AAPR and post-AAPR alone or liver function assessment systems.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Prognóstico , Carcinoma Hepatocelular/terapia , Fosfatase Alcalina , Neoplasias Hepáticas/terapia , Albuminas , CatéteresRESUMO
The morphology of dodecane in a nanopore at temperatures typical in exploited or depleted oil reservoirs is investigated using molecular dynamics simulation. The dodecane morphology is found to be determined by interactions between interfacial crystallization and surface wetting of the simplified oil, while "evaporation" only plays a minor role. The morphology changes from an isolated, solidified dodecane droplet to a film with orderly lamellae structures remaining within, and finally to a film containing randomly distributed dodecane molecules, as the system temperature increases. In a nanoslit under the impact of water, since water wins against oil in surface wetting on the silica surface due to electrostatic interaction induced hydrogen bonding between water and the silanol group of silica, the spreading of dodecane molecules over the silica surface is impeded by this water confinement mechanism. Meanwhile, interfacial crystallization is enhanced, leading to always an isolated dodecane "droplet," with crystallization weakening as the temperature increases. Since dodecane is immiscible to water, there is no mechanism for dodecane to escape the silica surface, and the competition of surface wetting between water and oil determines the morphology of the crystallized dodecane droplet. For the CO2-dodecane system in a nanoslit, CO2 is an efficient solvent for dodecane at all temperatures. Therefore, interfacial crystallization rapidly disappears. The competition of surface adsorption between CO2 and dodecane is secondary for all cases. The dissolution mechanism is a clear clue for the fact that CO2 is more effective than water flooding in oil recovery for a depleted oil reservoir.
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Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Masculino , Feminino , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Análise de Sobrevida , Indução de Remissão , Doença Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Complexo de Proteínas Formadoras de Poros NuclearesRESUMO
AIM: To improve the accuracy of diagnosis of Rosai-Dorfman disease (RDD) by summarising the computed tomography (CT) and magnetic resonance imaging (MRI) characteristics. MATERIALS AND METHODS: The clinical manifestations, imaging findings, and pathological characteristics of 14 patients with histopathologically confirmed RDD were analysed retrospectively and a literature review was undertaken. RESULTS: Of the 14 patients, nine had multiple lesions and five had single lesions. Eight patients had extranodal lesions, while six had mixed-type lesions. In patients with head and neck lesions, plain CT/MRI revealed irregularly shaped, well-defined, homogeneous, and mainly progressive lesions, with marked homogeneous enhancement on multiphasic contrast-enhanced imaging. One patient had dural lesions, one of which iso-intense to grey matter, with patchy hypo-intensity on T2-weighted imaging, meningeal tail signs, and characteristic crabfoot-like enhancement. Three patients with skeletal system involvement exhibited osteolytic bone destruction without sclerosis at the edges, associated soft-tissue masses, or periosteal reactions. Two patients had well-defined subcutaneous lesions, inhomogeneous density, and progressive parenchymal enhancement on contrast-enhanced CT. One patient had multiple intestinal lesions with inhomogeneous nodular thickening of the blind ascending colon and ileum, with marked and progressive enhancement. CONCLUSION: RDD involvement is mainly multifocal, primarily in the head and neck regions. Plain CT/MRI revealed well-defined, irregularly shaped lesions with homogeneous density/signal, with marked and progressive enhancement on multiphasic contrast-enhanced imaging; however, histopathology is still required to confirm the diagnosis of RDD.
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Histiocitose Sinusal , Cabeça/patologia , Histiocitose Sinusal/diagnóstico por imagem , Histiocitose Sinusal/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVE: Current risk assessment tools for osteoporosis have inconsistent performance across different cohorts, making them difficult for clinical practice. This study aimed to evaluate a simple screening index comprising years since menopause (YSM) and body mass index (BMI) that identifies postmenopausal Singaporean women with a greater likelihood of low bone mass. METHODS: The study used data from 188 treatment-naïve postmenopausal women. The associations between low bone mass and different demographic variables, including age, YSM and BMI, were assessed using multivariable logistic regression. Diagnostic performance of the calculated screening index was compared to the Osteoporosis Self-Assessment Tool for Asians (OSTA) and the Fracture Risk Assessment Tool (FRAX®). RESULTS: YSM and BMI were significantly associated with low bone mass. The area under the receiver operating characteristic curves was 0.803 for the screening index, 0.759 for the OSTA, 0.683 for the FRAX® (major osteoporotic fracture probability [MOFP]) and 0.647 for the FRAX® (hip fracture probability [HFP]). Non-parametric Spearman's correlation between the screening index and the other models was 0.857 with the OSTA score, 0.694 with the FRAX® (HFP) and 0.565 with the FRAX® (MOFP) (p < 0.0005). CONCLUSIONS: The diagnostic performance of the screening index comprising YSM and BMI was equivalent to the OSTA and the FRAX®. A risk chart was developed for clinicians to identify and recommend subjects for a further dual-energy X-ray absorptiometry scan. Validation of this model in larger and more diverse cohorts is required.
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Osteoporose , Fraturas por Osteoporose , Absorciometria de Fóton , Povo Asiático , Índice de Massa Corporal , Densidade Óssea , Feminino , Humanos , Programas de Rastreamento , Menopausa , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Medição de Risco , Fatores de Risco , Singapura/epidemiologiaRESUMO
The COVID-19 swept across the countries and regions all over the world in the past one year. The marketing of an effective and safe COVID-19 vaccine is expected to control the spread of the disease. A placebo-controlled field efficacy trial is generally considered in the pivotal study of COVID-19 vaccine to observe whether it is able to reduce the incidence rate of the disease effectively. This paper is to introduce and discuss the considerations in study design and the choice of endpoint, statistical evaluation methods, primary estimand choosing and the strategies to various intercurrent events in the COVID-19 efficacy trials.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Projetos de Pesquisa , SARS-CoV-2RESUMO
Objective: To investigate the clinicopathological characteristics of pancreatic lesions in children. Methods: The clinicopathological data of pancreatic lesions in children were analyzed including 42 cases of pancreatic tumors diagnosed from January 2000 to May 2021 in Guangzhou Women's and Children's Medical Center, Guangzhou, China. Histological and immunohistochemical assessments were performed. Related literature was reviewed. Results: The 42 pediatric patients with pancreatic lesions aged 1 day to 12 years (mean, 4.25 years). There were 23 males and 19 females. Clinical presentations included abdominal masses, abdominal pain, vomiting and persistent hypoglycemia after birth. Ultrasound and computerized tomography examination showed space-occupying pancreatic lesions in 31 cases, but no detectable pancreatic lesions in 11 cases. Histologically, among the 42 cases, 22 cases (52.4%) were neoplastic, including 18 cases of epithelial origin. Nine cases of pancreatoblastoma showed that the epithelial tumor cells were arranged in a trabecular pattern, with squamous nests. Six cases of solid-pseudopapillary tumors revealed hemorrhagic and necrotic cysts and monomorphic epithelioid cells arranged in solid sheets, nests or pseudopapillae. Two cases of neuroendocrine tumors showed tumor cells arranged in cords or nests; one case had a mitotic count of about 3/10 high power field, and a Ki-67 index of about 5%, which was consistent with G2 neuroendocrine tumor; the other case showed tumor cells with cytological atypia, brisk mitoses, about 25/10 HPF and a Ki-67 index of about 80%, consistent with small-cell type neuroendocrine carcinoma. The case of acinar cell carcinoma showed high cellularity, tumor cells in solid, cord-like or acinar-like arrangement with little stroma, and monotonous tumor cells with single distinct nucleolus. There were 4 cases of mesenchymal tumors, including 3 cases of Kaposi's hemangioendothelioma and 1 case of inflammatory myofibroblastic tumor. Among the 20 cases (47.6%) of non-neoplastic lesions, there were 11 cases of hyperinsulinism with ATP-sensitive potassium channel abnormality (HAPCA). Severn cases of diffuse type HAPCA in which the islets scattered between the pancreatic acinar tissue, enlarged, and prominent nuclei. Three cases of focal type HAPCA showed pancreatic islet hyperplasia in the form of nested nodules (0.6-1.5 cm). One case of atypical type HAPCA had extensive islet hyperplasia in pancreatic tissue, and scattered proliferation of nest-like nodules was noted. There were also 7 cases of pseudocyst and 2 cases of congenital cyst. Immunohistochemically, pancreatoblastomas were diffusely positive for CKpan, CK8/18, and ß-catenin (nuclear staining of squamous nests only). Solid-pseudopapillary tumors expressed CD10, cyclin D1, CD99, vimentin, CD56, and ß-catenin (nuclear staining). Neuroendocrine tumors were positive for CK, Syn, NSE, CgA, CD56, and ß-catenin (membranous staining). The acinar cell carcinoma was positive for CK8/18, trypsin, and ß-catenin (membranous staining). Conclusions: Pancreatic lesions in children have a wide range of histopathological types. HAPCA is the most common lesion of newborns. Pediatric pancreatic tumors are rare and mostly malignant. It is important to recognize them and make correct pathological diagnoses.
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Carcinoma de Células Acinares , Carcinoma de Células Escamosas , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Carcinoma de Células Acinares/patologia , Criança , Feminino , Humanos , Hiperplasia , Recém-Nascido , Antígeno Ki-67 , Masculino , Neoplasias Pancreáticas/metabolismo , beta Catenina/análiseRESUMO
Objective: To examine the efficacy and safety of endothelin receptor antagonists (ERA) combined with phosphodiesterase 5 inhibitors (PDE5i) in the treatment of pulmonary artery hypertension (PAH). Methods: Computer-based retrieval was performed on PubMed, Cochrane Library, CNKI, Wanfang, and VIP database (up to February 12th, 2021). Randomized controlled trials about endothelin receptor antagonists (ERAs) or PDE5i in patients with PAH were collected. The change of 6-minute walking distance (6MWD) in 12-16 weeks was used as primary outcome index. Case fatality rate, worsening clinical events, WHO functional class (FC) improvement, adverse events (AEs), serious adverse events (SAE) were the key secondary outcomes indicators. STATA 16.0 software was used for network meta-analysis, and the pooled estimates of odds ratios (ORs) or weighted mean differences (WMDs) and 95% confidence intervals (CIs) of the results were shown. To help explain ORs and WMDs, we used the surface under the cumulative ranking curve (SUCRA) to calculate the probability of each intervention. Results: We included 29 trials with 5 949 participants. In network meta-analysis, Bosentan combined with Sildenafil (WMD=53.93, 95%CI=6.19-101.66) had shown the greatest improvement in 6MWD compared with placebo, followed by Bosentan combined with Tadalafil (WMD=50.84, 95%CI=7.05-94.62), Ambrisentan combined with Tadalafil (WMD=46.67, 95%CI=15.88-77.45), Bosentan (WMD=29.44, 95%CI=5.86-53.02), Ambrisentan (WMD=23.90, 95%CI=0.31-47.48) and Macitentan (WMD=21.57, 95%CI=2.45-40.69). According to SUCRA, the effects of different intervention measures on improving 6MWD in patients with arterial pulmonary hypertension were as follows: Bosentan+Sildenafil (82.9%)>Bosentan+Tadalafil (78.4%)>Ambrisentan+Tadalafil (77.1%)>Bosentan (49.2%)>Sildenafil (48.5%)>Ambrisentan (40.3%)>Macitentan (37.3%)>Tadalafil (33.0%)>Placebo (3.3%). For the WHO functional class, Sildenafil (OR=2.90, 95%CI=1.04-8.08) was optimal compared with placebo, followed by Bosentan (OR=2.15, 95%CI=1.15-4.04), and there was no significant difference in the rest. For clinical worsening, Bosentan combined with Tadalafil (OR=0.08, 95%CI=0.01-0.49) performed best compared with placebo, followed by Bosentan (OR=0.20, 95%CI=0.11-0.38), Bosentan combined with Sildenafil (OR=0.21, 95%CI=0.09-0.46), Ambrisentan combined with Tadalafil (OR=0.27, 95%CI=0.15-0.50), Sildenafil (OR=0.33, 95%CI=0.17-0.66) and Tadalafil (OR=0.44, 95%CI=0.21-0.90). There was no statistical difference between all interventions and placebo in terms of the incidence of adverse events and serious adverse events. For case fatality rate, Ambrisentan (OR=0.28, 95%CI=0.11-0.74) was statistically superior to placebo and there was no statistics difference in the rest. Conclusions: The combination therapy of ERAs and PDE5i performed well in the short-term improvement of motor function. Furthermore, there was no significant difference with monotherapy in terms of safety. However, it is worth emphasizing that the choice of treatment should be based on the patient's individualized situation and the patient's requirements.
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Inibidores da Fosfodiesterase 5 , Hipertensão Arterial Pulmonar , Anti-Hipertensivos/uso terapêutico , Bosentana , Antagonistas dos Receptores de Endotelina/uso terapêutico , Humanos , Metanálise em Rede , Inibidores da Fosfodiesterase 5/uso terapêutico , Resultado do TratamentoRESUMO
The objective of this study was to investigate the effects of baicalein on apoptosis of HeLa human cervical cancer (CC) cells and to elucidate the underlying mechanism. HeLa cells were treated with 20, 50, 100, or 200 µmol/L baicalein for 24, 36, and 48 hours, and CCK-8 assays were used to detect cell viability, and flow cytometry was performed to assess apoptosis rate. Reverse-transcription quantitative PCR was used to measure ERK1/2, p38, and JNK mRNA levels in HeLa cells, and western blotting was performed to measure ERK1/2, p38, and JNK protein levels. The CCK-8 assay showed that the OD value of HeLa cells gradually decreased with increasing baicalein concentrations (P < 0.01) and treatment time (P < 0.01). These results indicated a negative time- and dose-dependent effect of baicalein on HeLa cells. Baicalein treatment of HeLa cells significantly increased apoptosis rate (P < 0.01). In HeLa cells treated with 50 or 200 µmol/L baicalein for 24 h, expression levels of ERK1/2 and p38 mRNA were significantly reduced, whereas that of JNK mRNA was increased (P < 0.01). The levels of phosphorylated ERK1/2 and p38 were significantly reduced, and the level of JNK protein was increased (P < 0.01). Taken together, baicalein appeared to exert anti-cancer effects on HeLa cells through induction of apoptosis and regulation of the ERK/p38/mitogen-activated protein kinase pathway.
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Neoplasias do Colo do Útero , Proteínas Quinases p38 Ativadas por Mitógeno , Apoptose , Regulação para Baixo , Feminino , Flavanonas , Células HeLa , Humanos , Sistema de Sinalização das MAP Quinases , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
Objective: To find the biomarkers that accurately predict the survival of patients with esophageal squamous cell carcinoma (ESCC). Methods: The immune related genes that were significantly related to the overall survival (OS) of patients with ESCC were screened from The Cancer Genome Atlas (TCGA) database to construct a prognostic risk score model. The prognoses of the high-risk and low-risk groups were compared by Kaplan-Meier method. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve. Tumor tissue samples of 83 patients with pathological diagnosis of ESCC were collected from Anyang Cancer Hospital for external verification. Cox regression analysis was used to comprehensively evaluate the effects of prognostic risk score and various clinical characteristics on OS of patients with ESCC. Results: Seven immune-related genes that were significantly related to survival prognosis were selected from the TCGA database and included in the prognostic risk score model, which were S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2. The 1- and 2-year survival rates of the low-risk group (40 cases) were 94.3% and 82.5%, respectively, while those of the high-risk group (40 cases) were 75.9% and 32.9%, respectively.The prognosis of the high-risk group was worse than that of the low-risk group (P<0.001). The 83 external validation samples obtained consistent results by using the prognostic risk score model. The prognostic risk score was positively correlated with the content of CD4(+) T lymphocytes in ESCC (r(s)=0.259, P=0.020), but not correlated with the content of B lymphocytes, CD8(+) T lymphocytes, neutrophils, macrophages or dendritic cells (P>0.05). Conclusions: S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2 were risk genes significantly associated with OS of patients with ESCC. The prognostic risk score was an independent prognostic factor for the OS of patients with ESCC, and it was correlated with the content of CD4(+) T lymphocytes in ESCC tissue.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , Biomarcadores Tumorais/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Glicoproteínas , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Estimativa de Kaplan-Meier , Prognóstico , Fatores de RiscoRESUMO
Objective: To investigate the clinicopathological features of gonadal neoplastic related lesions in children with disorders of sexual development (DsD). Methods: The clinical manifestations, chromosomal karyotype, histology and immunophenotype of 12 cases of neoplastic related lesions from Guangzhou Women and Children's Medical Center, Guangzhou were analyzed during Jan 2015 to May 2020. Results: Twelve cases of neoplastic related lesions were screened in 205 cases of DsD, and 6 patients with gonadal germ cell neoplasia aged 3-13 years with an average age of 8.3 years. There were 2 males and 4 females. Clinical features showed malformation of external genitalia in 2 cases, short stature in 2 cases, clitoral enlargement in 1 case, lower abdominal pain and a huge pelvic mass in 1 case. Chromosomal karyotyping of peripheral blood showed 2 cases of 46XY and 4 cases of 45X/46XY. Fourteen gonadal specimens were examined. Microscopically, 1 case showed dysgerminoma in left ovary, and malignant mixed germ cell tumors in right ovary, as well as gonadoblastoma (GB) and undifferentiated gonadal tissue (UGT). The remaining 5 cases were all precursor lesions of germ cell tumor. Six specimens showed GB, 3 of UGT, and 3 specimens showed germ cell neoplasia in situ (GCNIS), one of which was accompanied by intratubular seminoma and 1 was GB with GCNIS. The other 6 patients with DsD were aged from 8 months to 2 years and 5 months, including 5 males and 1 females. Clinical manifestations showed 5 cases of hypospadias and 1 case of bilateral indirect inguinal hernia. Microscopically, 6 cases showed maturation delay of gonocytes in seminiferous tubules. Immunohistochemically, the primordial germ cells/gonocytes expressed OCT3/4, PLAP and c-KIT in the 12 cases. Conclusion: Gonadal neoplasia in children with DsD is mainly precursor lesions of germ cell tumor and improved understanding of these lesions is of great significance.
Assuntos
Transtornos do Desenvolvimento Sexual , Gonadoblastoma , Neoplasias Embrionárias de Células Germinativas , Neoplasias Ovarianas , Neoplasias Testiculares , Criança , Feminino , Gonadoblastoma/genética , Gonadoblastoma/cirurgia , Humanos , MasculinoRESUMO
AIM: Ultrasound-guided transversus abdominis plane and rectus sheath block (TAPRSB) decreases pain scores and narcotic use postoperatively after colorectal surgery (CRS). It is unclear if the effectiveness of TAPRSB varies according to whether it is performed preoperatively or postoperatively. Our aim was to investigate this. METHOD: We compared patients who underwent preoperative TAPRSB or postoperative TAPRSB during minimally invasive CRS. Primary end-points were pain scores and oral morphine milligram equivalent (MME) use postoperatively. Secondary end-points included perioperative factors affecting pain scores and postoperative MME. Summary statistics and univariate analysis by nonparametric tests were utilized. The mixed-effect model was applied to model the repeatedly measured pain score. RESULTS: From April 2015 until May 2018 168 patients received TAPRSB before (115) or after (53) minimally invasive CRS. The cohort included 79 (47.0%) women, and had an average age of 59.11 (±12.32) years and mean body mass index of 28.32 (±5.82) kg/m2 . Indication for surgery was cancer in 66 (39.3%), polyp in 43 (25.6%) and diverticulitis in 43 (25.6%). Right colectomy was performed in 61 (36.3%), low anterior resection in 46 (27.4%) and sigmoid colectomy in 40 (23.8%) patients. The demographics of the groups were similar. Postoperative TAPRSB was only associated with lower pain scores at 12 h postoperatively. As secondary outcomes, average pain scores and MME were lower in patients who were older, had right colectomy or intracorporeal anastomosis. CONCLUSIONS: Postoperative TAPRSB resulted in lower pain scores than preoperative TAPRSB 12 h after minimally invasive CRS, but otherwise no differences were seen in pain scores or MME use.
Assuntos
Cirurgia Colorretal , Dor Pós-Operatória , Músculos Abdominais , Analgésicos Opioides/uso terapêutico , Anestésicos Locais , Colectomia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologiaRESUMO
Objective: To evaluate the performance of Hybribio human papillomavirus (HPV) typing test kit for high risk HPV-DNA typing detection in screening of cervical precancer lesions. Methods: A total of 9 914 women were recruited in Henan, Shanxi, and Guangdong provinces from June to July 2017. All women underwent HPV DNA test. The women who diagnosed as HPV positive and cytological examination ≥ atypical squamous cells of undetermined significance (ASCUS) or HPV negative and cytological examination≥low-grade squamous intraepithelial lesions (LSIL) underwent colposcopy biopsy and pathological examination. Using the pathological diagnosis as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence interval (CI) of high-risk HPV and HPV16/18 tests were calculated. Results: The mean age of 9 914 subjects was (45.0±9.3) years old. Among them, 1 302 subjects were detected as high risk HPV positive, including 211 of HPV16 positive and 64 of HPV18 positive. According to the pathological gold standard of cervical intraepithelial neoplasia grade 2 (CIN2) or worse, the sensitivity and specificity of high risk-HPV and HPV 16/18 for triaging ASCUS women were 90.6% (95%CI: 75.8%-96.8%) and 78.0% (95%CI: 74.5%-81.2%) as well as 56.3% (95%CI: 39.3%-71.8%) and 95.7% (95%CI: 93.8%-97.1%), respectively. The sensitivity and specificity of high risk-HPV and HPV 16/18 for cervical precancer lesions screening were 95.1% (95%CI: 88.1%-98.1%) and 87.6% (95%CI: 86.9%-88.2%) as well as 65.9% (95%CI: 55.1%-75.2%) and 97.8% (95%CI: 97.5%-98.1%), respectively. Conclusions: The Hybribio HPV test kit has a relative high sensitivity and specificity for cervical precancer lesions screening and ASCUS triaging. It is reliable for HPV DNA detection and cervical cancer screening.
Assuntos
Detecção Precoce de Câncer , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Teste de Papanicolaou , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Biópsia , Colo do Útero/patologia , Colo do Útero/virologia , Colposcopia , DNA Viral/análise , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Valor Preditivo dos Testes , Gravidez , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
Objective: To evaluate the effects of exposure of fine particle matter (PM2.5) and ozone (O3) in Beijing as the main pollutants on olfaction of SD rats. Methods: In October 16, 2018, twenty 8-week-old SD rats were randomly divided into two groups, 10 rats in the exposure group and 10 rats in the control group. They were fed in air pollutant exposure system and clean experimental environment respectively, and the concentrations of PM2.5 and O3 in each system were measured. The degree of olfaction damage of SD rats at different feeding time was assessed by using the buried food test (BFT). The difference of BFT time between the two groups was analyzed by performing the repeated measures analysis of variance. Results: The results showed that the concentrations of PM2.5 and O3 in the exposure group were (22.65±11.47) µg/m3 and (12.36±5.87) µg/m3, respectively, while those in the control group were both 0 µg/m3. The repeated measures analysis of variance showed that the time of BFT in the exposure group was longer than that in the control group (F=6.49, P=0.031). With the increase of feeding time, the time of BFT was prolonged (F=61.69, P<0.001). Conclusion: Exposure to PM2.5 and O3 in the atmosphere might lead to olfaction damage in rats.