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Objective: To investigate the association between positive anti-thyroid peroxidase antibody (TPOAb) and/or anti-thyroglobulin antibody (TgAb) and the occurrence of thyroid immune-related adverse events (irAEs) in patients with malignant tumors who treated with immune checkpoint inhibitors (ICIs). Methods: A case-control study. A total of 116 patients with malignant tumor who received ICIs treatment and underwent thyroid function evaluation at Peking Union Medical College Hospital from January 2017 to April 2023 were enrolled retrospectively, including 77 males and 39 females, with a median age of (M(Q1, Q3)) 63.0 (55.0, 70.0) years. The patients were divided into the euthyroid group (n=58) and the thyroid irAEs group (n=58) according to whether thyroid irAEs occurred after ICIs treatment. The clinical characteristics and baseline anti-thyroid antibodies associated with the occurrence of thyroid irAEs after ICIs treatment in patients with malignant tumors were evaluated. Variables with statistical significance in univariate analysis were included in multivariate logistic regression model to analyze the risk factors for thyroid irAEs in patients with malignant tumors who received ICIs treatment. Results: In irAEs group, therewore 4 (3.4%) cases of clinical thyrotoxicosis, 23(19.8%) cases of subclinical thyrotoxicosis, 23 (19.8%) cases of clinical hypothyroidism, and 8(6.9%) cases of subclinical hypothyroidism. The positive rate of anti-thyroid antibodies at baseline in the thyrioid irAEs group was higher than that in the euthyroid groupï¼»16/58ï¼27.6%ï¼vs 3/58ï¼5.2%ï¼ï¼P=0.001ï¼½. After at least one course of ICIs treatment, the incidence of thyroid irAEs in patients with positive anti-thyroid antibodies at baseline was 84.2% (16/19), whereas it was 43.3% (42/97) in patients with negative anti-thyroid antibodies(P=0.001). Univariate logistic regression analysis showed that gender (OR=2.812, 95%CI:1.257-6.293), baseline thyroid autoantibodies were positive (OR=6.984, 95%CI: 1.909-25.547), baseline TgAb positivity (OR=8.909, 95%CI: 1.923-41.280), and baseline TPOAb positivity (OR=7.304, 95%CI: 1.555-34.308) were associated with thyroid irAEs (all P<0.05). Multivariate logistic regression analysis indicated that baseline TgAb positivity (OR=7.637, 95%CI: 1.617-36.072) was a risk factor for thyroid irAEs (P=0.01). Conclusions: The incidence of thyroid irAEs is higher in patients who are positive for baseline TPOAb and/or TgAb compared to those who are negative for TPOAb and TgAb. Patients with positive TgAb at baseline are at high risk of developing thyroid irAEs.
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Hipotireoidismo , Doenças do Sistema Imunitário , Neoplasias , Tireotoxicose , Masculino , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos de Casos e Controles , Estudos Retrospectivos , Iodeto Peroxidase , Autoanticorpos , Hipotireoidismo/induzido quimicamente , Neoplasias/tratamento farmacológicoRESUMO
Objective: To investigate the value of net water uptake (NWU) for predicting early neurological improvement (ENI) after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke. Methods: A case-control study. A total of 132 patients (80 men, 52 women, median age 68 years) with acute anterior circulation large vessel occlusive stroke receiving endovascular treatment were retrospectively analyzed at Jinling Hospital from October 2014 to September 2019. Patients were divided into two groups based on the occurrence of ENI, which was defined as either an improvement of NIHSS score of ≥4 points, or an NIHSS score of 0 or 1 at 24 hours after endovascular treatment. The rank sum test, Chi square test, and other methods were used to compare differences in baseline characteristics between the two groups. Logistic regression analysis was used to investigate independent predictors of postoperative ENI. Receiver operating characteristic curve analysis used to assess the capacity of NWU to predict ENI. Results: Of the 132 patients in the study, ENI occurred in 47 and did not occur in 85. In multivariate logistic regression analysis age [odds ratio (OR)=0.940, 95% confidence interval (CI) 0.903-0.979, P=0.003], time from stroke onset to puncture (OR=0.995, 95%CI 0.991-0.999, P=0.025), time from puncture to recanalization/end of operation (OR=0.985, 95%CI 0.974-0.996, P=0.007), NWU (OR=0.762, 95%CI 0.620-0.937, P=0.010), and mTICI (OR=1.644, 95%CI 1.043-2.590, P=0.032) were predictive factors for ENI. Receiver operating characteristic curve analysis indicated that NWU could effectively predict ENI (area under the curve=0.642, 95%CI 0.543-0.741, P=0.007), and prediction accuracy was improved when it was combined with other clinical parameters. Conclusion: NWU is an independent predictor of ENI in patients with acute anterior circulation large vessel occlusive stroke undergoing endovascular treatment.
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Peri-operative dexmedetomidine can reduce rates of delirium immediately after surgery. We aimed to assess the effect of dexmedetomidine on cognition up to six postoperative months and its association with changes in serum concentrations of brain-derived neurotrophic factor on the third and seventh postoperative days. We randomly allocated 535 patients aged 65 years or more undergoing scheduled gastro-intestinal laparotomy to: intra-operative dexmedetomidine, 0.5 µg.kg-1 bolus followed by 0.4 µg.kg-1 .hr-1 infusion (n = 269), or placebo (n = 266). Dexmedetomidine reduced the rate of cognitive impairment: on the third postoperative day, 40/269 vs. 65/266, p = 0.006; on the seventh postoperative day, 31/269 vs. 49/266, p = 0.03 and at one postoperative month, 42/250 vs. 61/248, p = 0.04. Cognitive impairment at seven postoperative days was associated with changes in brain-derived neurotrophic factor concentrations on the third and seventh postoperative days; area under the receiver operating characteristic curve 0.63, p < 0.001 and 0.58, p = 0.016, respectively. Intra-operative dexmedetomidine reduced cognitive decline up to one postoperative month in elderly patients undergoing scheduled laparotomy, which was associated with changes in serum brain-derived neurotrophic factor.
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Disfunção Cognitiva/prevenção & controle , Dexmedetomidina/farmacologia , Hipnóticos e Sedativos/farmacologia , Cuidados Intraoperatórios/métodos , Complicações Pós-Operatórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Fator Neurotrófico Derivado do Encéfalo/sangue , Disfunção Cognitiva/sangue , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/sangue , Estudos ProspectivosRESUMO
Objective: To observe the changes of sex hormone and sex hormone-binding globulin (SHBG) levels in young male patients with hyperthyroidism before and after antithyroid drug (ATD) treatment. Methods: Between January 2015 and July 2016, forty male patients with hyperthyroidism aged 19-52 years (with an median age of 33.1 years) were enrolled in the Department of Endocrinology of Peking Union Medical College Hospital. Blood samples were taken before treatment and at 1 month, 2 months, 3 months and 5 months after treatment to evaluate thyroid function, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone(T), free testosterone(FT), estradiol(E2), prolactin and SHBG. Results: A total of 40 patients were enrolled but only 35 patients completed the follow-up. The patients had high levels of thyroid function, SHBG and sex hormones before treatment. Before treatment, free thyroxine (FT(4)), free triiodothyronine (FT(3)), SHBG, LH, estradiol, testosterone and free testosterone was (0.30±0.12) pmol/L, (9.68±4.73) pmol/L, (146±111) nmol/L, (8.41±3.61) U/L, (19.9±7.7) pmol/L, (29.9±9.5) nmol/L and (0.24±0.08) nmol/L, respectively. After treatment, the level of triiodothyronine, thyroxine, FT(3) and FT(4) gradually decreased to normal (all P<0.001). Thyroid stimulating hormone (TSH) gradually increased to normal (P<0.001). LH and estradiol levels gradually decreased (all P<0.001). FSH decreased but the difference was not statistically significant. Prolactin did not change significantly. Testosterone and SHBG levels decreased significantly while the levels of free testosterone, free testosterone percentage (FT%), bio-available testosterone (BAT), bio-available testosterone percentage (BAT%), free androgen index (FAI) gradually increased and stabilized (all P<0.001). The difference was not statistically significant between T/LH and E2/LH before and after treatment (all P>0.05). However FT/LH gradually increased and its difference was statistically significant (P<0.001). Conclusion: The levels of LH, estradiol, testosterone and SHBG in male patients with hyperthyroidism significantly increased, while the free testosterone level decreased, but they all gradually returned to normal with the lowering of thyroid hormone levels during ATD treatment.
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Antitireóideos/uso terapêutico , Hipertireoidismo , Adulto , Idoso , Estradiol , Hormônio Foliculoestimulante , Hormônios Esteroides Gonadais , Humanos , Hipertireoidismo/tratamento farmacológico , Hormônio Luteinizante , Masculino , Pessoa de Meia-Idade , Globulina de Ligação a Hormônio Sexual , Testosterona , Adulto JovemRESUMO
Rabies is one of the major public health problems in China, and the mortality rate of rabies remains the highest among all notifiable infectious diseases. A meta-analysis was conducted to investigate the post-exposure prophylaxis (PEP) vaccination rate and risk factors for human rabies in mainland China. The PubMed, Web of Science, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical and Wanfang databases were searched for articles on rabies vaccination status (published between 2007 and 2017). In total, 10 174 human rabies cases from 136 studies were included in this meta-analysis. Approximately 97.2% (95% confidence interval (CI) 95.1-98.7%) of rabies cases occurred in rural areas and 72.6% (95% CI 70.0-75.1%) occurred in farmers. Overall, the vaccination rate in the reported human rabies cases was 15.4% (95% CI 13.7-17.4%). However, among vaccinated individuals, 85.5% (95% CI 79.8%-83.4%) did not complete the vaccination regimen. In a subgroup analysis, the PEP vaccination rate in the eastern region (18.8%, 95% CI 15.9-22.1%) was higher than that in the western region (13.3%, 95% CI 11.1-15.8%) and this rate decreased after 2007. Approximately 68.9% (95% CI 63.6-73.8%) of rabies cases experienced category-III exposures, but their PEP vaccination rate was 27.0% (95% CI 14.4-44.9%) and only 6.1% (95% CI 4.4-8.4%) received rabies immunoglobulin. Together, these results suggested that the PEP vaccination rate among human rabies cases was low in mainland China. Therefore, standardised treatment and vaccination programs of dog bites need to be further strengthened, particularly in rural areas.
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Objective: Using clinical "big data" , to investigate the factors that affect the levels of thyroid hormones, and to explore the partitioning criteria for reference intervals (RI) of these hormones. Methods: An observation study was conducted. Information of 107 107 individuals undergoing routine physical examination in Peking Union Medical College Hospital from September 1(st,) 2013 to August 31(st,) 2016 was collected, thyroid hormone of these subjects were detected. To explore the test results distribution and differences of TSH, FT4 and FT3 by gender and age; according to the seasonal division standard of China Meteorological Administration, the study period was divided into four seasons, and the seasonal fluctuation on TSH was analyzed.To define the appropriate partition by gender, age and season according to significant difference analysis. Results: In male and female, the distributions of TSH were 1.779(0.578-4.758), 2.023(0.420-5.343)mU/L, respectively, and the level of TSH in female was higher than in male (Z=-37.600, P<0.001). The distributions of FT4 were 0.127(0.098-0.162), 0.117(0.091-0.151) µg/L, the distributions of FT3 were 3.33(2.47-3.74), 3.01(2.35-3.57)ng/L. And the level of FT4, FT3 in female were significantly lower than in male (Z=-94.000, -154.600, all P<0.001). Furthermore, males were divided into two groups by 65 years old and female were divided by 50 years old, respectively, and the distributions of TSH in male and female of older group were 1.818(0.528-5.240), 2.111(0.348-5.735)mU/L, in younger group were 1.778(0.582-4.696), 1.991(0.427-5.316)mU/L. The level of TSH in older group was significantly higher than in younger group (Z=-2.269, -10.400, all P<0.05), and the distribution of TSH in older group was much wider than in younger. The distribution of whole in spring, summer and autumn was 1.869( 0.510-5.042)mU/L, in winter was 1.978(0.527-5.250) mU/L, and the difference between them had statistical significance (Z=-15.000, P<0.001). Conclusions: Gender and age significantly affect the serum levels of TSH, FT4, and FT3, the distribution of TSH in female and elder group are wider than in male, and that of FT4, FT3 are lower.Seasons significantly affect the serum TSH level, the peak value is observed in winter. There are obviously differences between "rough" RIs and manufacture recommended RIs. Each laboratory should establish reference intervals for thyroid hormones on the premise of appropriate grouping.
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Hormônios Tireóideos/análise , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estações do Ano , Testes de Função TireóideaRESUMO
Objective: To study the clinical characteristics of primary hypoparathyroidism in adults. Methods: The clinical data of 200 cases with adult-onset primary hypoparathyroidism in Peking Union Medical College Hospital during December 1987 to December 2015 were collected and analyzed retrospectively. Among them, 128 cases were followed up for a median period of 3 years. Results: The major manifestations at their first visits were tetany and numbness in the distal extremities(81.5%, 163/200 and 62.0%, 124/200). Thirty-two percent of the cases (62 cases) had history of seizures, and 60.9%(98/161) and 74.4%(96/129) of them were with intracerebral calcifications and cataracts, respectively.Most of subjects(155/200)had more than one year delay in diagnosis. Hypercalciuria occurred in 67.2%(86/128) of the cases during the follow-up. No significant differences in the clinical characteristics and biochemical markers between the hypercalciuria subjects and the non-hypercalciuria subjects. Renal nephrocalcinosis or stones were found in 6.5%(5/77) of the cases, and kidney function decreased in 6.6%(6/91) of the patients. Kidney function was negatively associated with age and duration of disease. Conclusions: The predominant manifestations of primary hypoparathyroidism in adults included tetany and numbness in the distal extremities and seizures. It is often misdiagnosed. Calcium supplement combined with vitamin D or its metabolites effectively relieve clinical symptoms and signs. The serum and urinary calcium levels should be monitored frequently to reduce renal complications.
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Calcitriol/uso terapêutico , Cálcio , Hipocalcemia/tratamento farmacológico , Hipoparatireoidismo/complicações , Hipoparatireoidismo/diagnóstico , Hormônio Paratireóideo/sangue , Vitamina D/uso terapêutico , Adulto , Calcitriol/efeitos adversos , Cálcio/sangue , Cálcio/urina , Feminino , Humanos , Hipocalcemia/sangue , Hipocalcemia/urina , Hipoparatireoidismo/sangue , Hipoparatireoidismo/terapia , Hipoparatireoidismo/urina , Rim/fisiopatologia , Masculino , Nefrocalcinose/epidemiologia , Estudos Retrospectivos , Convulsões/etiologia , Albumina Sérica/análiseRESUMO
Objective: To develop and validate an autoverification system for biochemistry and immunology test results for application in routine work. Methods: Algorithms was designed and translated into the laboratory information system. Parameters including verify limit, delta check, logic relation between tests was set up in the system. Verification rate of every test and the causes of fails were analyzed, according to which the system and parameters were modified. The autoverified reports were evaluated by chief technicians. Only when all of the autoverified results pass the evaluation, the system applied for routine work of releasing the results. Autoverification rate and turnaround time(TAT) were calculated for evaluation of the efficiency of the system. Results: A brand new autoverification system was developed and applied for routine work. The autoverification rate for each single test was 91.1%-96.6%. The autoverification rate for reports was 74%. With the autoverification system, the media of TAT reduced from 111.6(53.9-270.7) min to 87.2(45.4-202.4) min, whereas the time from instrument finishing analysis to releasing the reports reduced from 18.6(1.0-99.3) min to 0.1(0-58.3)min. The number of staff specified for results validation reduced from three to one. Conclusions: The newly developed system can be used for autoverification of biochemistry and immunology test results. The autoverification system can greatly reduce TAT and raise working efficiency. It's essential to employ carefully designed algorithm, appropriate parameters and comprehensive evaluation when developing a new autoverification system.
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Química Clínica , Sistemas de Informação em Laboratório Clínico , Algoritmos , HumanosRESUMO
Internal transcribed spacer 1 (ITS1) sequences from wild-type Exopalaemon carinicauda (N = 124) from the East China Sea were amplified and sequenced. Sequences were polymorphic and ranged from 388 to 583 bp in length. The average content of GC in sequences was significantly higher than that of AT. Altogether, 604 mutant sites with 123 haplotypes were detected; 46.7% were polymorphic sites. The genetic diversity index of population Y was highest, and the lowest was population X. Eight microsatellite sequences were detected; the most-repeated sequences were (GA)n, (AG)n, (GT)n, (TG)n, (TC)n, and (CT)n. Analysis of molecular variance revealed that genetic differentiation among the four populations were very weak, or modest. A molecular evolutionary tree was constructed using the neighbor-joining method and MEGA 6.0, and the phyletic evolutionary relationships among several Palaemonidae species examined. The phylogenetic tree showed that individuals of the same species, as well as the species of the same genus, clustered together, consistent with morphological classifications.
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DNA Intergênico/genética , Palaemonidae/genética , Penaeidae/classificação , Penaeidae/genética , Animais , China , Genética Populacional , Filogenia , Alinhamento de SequênciaRESUMO
Objective: To investigate the status of knowledge, attitude and practice about first aid and influencing factors in key population, those who have frequent contacts with people and might be "first aid" promoter in general population of Beijing, and provide evidences for the promotion of first aid. Methods: This study was a cross-sectional survey based on the "Emergency Rescue Capacity Training Project". Using cluster sampling, we recruited 9 591 participants after the training in Beijing for survey with a self-designed questionnaire from October 2021 to March 2022. Results: In 9 591 participants, 98.58% knew the emergency call number, while only 32.00% knew how to identify sunstroke. The awareness rate of the definition of first aid and legal disclaimer were lower (63.61%, 75.91%). People's willingness to give first aid to others, including relative, acquaintance, stranger and vagrant, were different (χ2=822.82, P<0.001). People were more likely to give first aid to relative, acquaintance and stranger compared with vagrant (P<0.05). With the increase of psychological distance, the willingness to give first aid decreased (Z=-26.57, P<0.001). According to the results of Logistic regression analysis, older age, higher annual family income and higher awareness of first aid related knowledge were contributing factors for giving first aid. In 1 529 people who met emergency, only 66 people (4.32%)did not give any first aid. Conclusions: The key population in Beijing has high awareness of first aid related knowledge and positive attitude of first aid after training. A high proportion of people performed first aid to others. Age, annual family income and awareness of first aid related knowledge were contributing factors for giving first aid.
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Primeiros Socorros , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pequim , Estudos Transversais , RendaRESUMO
Objective: To analyze and summarize the diagnosis, treatment and prognosis of granulomatosis with polyangiitis (GPA) with nasal symptoms as the first clinical manifestation. Methods: The data of 18 patients of GPA with nasal mucosal symptoms as the first clinical manifestation from the Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University between 2005 and 2019 was collected, including 8 males and 10 females, aged from 5 to 68 years. Nasal endoscopy, imaging examination, laboratory examination, immunological and histopathological examination of nasal mucosa were completed. All patients were treated with glucocorticoid combined with cyclophosphamide and were followed up for 2 to 15 years. Descriptive statistical method was used for analysis. Results: All the 18 patients had the nasal mucosal symptoms as the first clinical manifestation, including nasal obstruction, running nose and epistaxis. Nasal endoscopy showed swelling, erosion, scab and bleeding of nasal mucosa, and 6 cases had nasal septal perforation. Nasal sinus CT scan showed high density shadow of sinus, as well as hyperostosis and osteosclerosis. CT imaging features of pulmonary showed nodular lesion or patchy infiltration in 12 patients and cavitation was found in 6 cases. Laboratory results showed that 13 cases were positive for anti-neutrophil cytoplasmic antibodies (ANCA), and 5 cases were negative. During follow-up period, thirteen patients were symptomatic controlled and survived; two patients died of disease progression; one patient gave up treatment and died; two patients were lost to follow-up. Conclusions: Nasal symptoms are the first clinical manifestation of GPA. Early diagnosis and early treatment with glucocorticoid combined with cyclophosphamide can effectively improve the survival rate.
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Granulomatose com Poliangiite , Seios Paranasais , Anticorpos Anticitoplasma de Neutrófilos , Ciclofosfamida , Endoscopia , Feminino , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico , Humanos , MasculinoRESUMO
BACKGROUND: This study was done to investigate imaging features of portal vein aneurysms (PVA) associated with multiple associated findings and discuss the value of three-dimensional multiphase contrast-enhanced MR angiography (3D DCE-MRA) in detecting PVA. PATIENTS AND METHODS: 3D DCE-MRA with comprehensive use of various post processing methods was performed in 10 PVA patients. Imaging features of these PVA were analyzed. RESULTS: Of the 10 patients, PVA were located in the splenic vein in three cases, in the intrahepatic portal vein in three cases, at the confluence of the superior mesenteric vein and splenic vein in two cases, and in the main portal vein in two cases. The maximal diameter of the PVA varied from 2.0 cm to 8.39 cm (mean±SD, 3.72±1.84 cm). There were several cases associated with multiple associated findings, such as cavernous transformation of the portal vein, arterio-portal fistulas, arteriovenous malformation and multiple aneurysms of the splenic artery. CONCLUSIONS: 3D DCE-MRA proved to be effective in detecting PVA, improving the diagnosis of associated findings, and in supplying more information for clinical treatment of PVA.
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Aneurisma/diagnóstico , Imageamento Tridimensional , Angiografia por Ressonância Magnética , Veia Porta/patologia , Adolescente , Adulto , Aneurisma/complicações , Aneurisma/patologia , China , Dilatação Patológica , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Veias Mesentéricas/patologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Veia Esplênica/patologia , Adulto JovemRESUMO
Objective: To analyze the method and effect of reconstruction of the orbital floor defect with preserved orbital contents after advanced maxillary sinus cancer resection. Methods: Thirty-three patients of T3/T4 stage maxillary sinus cancer with orbital invasion who were treated in Shandong Provincial Hospital from January 2010 to October 2016 were retrospectively analyzed, including 20 males and 13 females, aged from 12 to 80 years old. Patients were treated with appropriate surgical methods according to their clinical manifestation, imaging finding, invasion range, preoperative and intraoperative pathology. Surgical approaches such as maxillectomy, expanded maxillectomy and superstructure maxillectomy were used for patients with Medpor orbit floor repairment. Patients were followed up regularly after surgery, and the surgical efficacy was discussed by descriptive statistical method. Results: Of those 33 cases, 19 were squamous cell carcinoma, 8 were adenoid cystic carcinoma, 5 were inverted papilloma malignant transformation, and 1 was myoepithelial carcinoma in our study. After tumor resection and orbital floor repair, the orbital contents and eyeball function of all patients remained intact. During follow-up time ranged from 3 to 8 years, a total of 6 patients relapsed at 3 years and died of ineffective treatment. The survival rate was 81.8% (27/33). Conclusion: Tumor resection and Medpor orbital floor repair in maxillary sinus cancer patients with orbital invasion can preserve the function of the eyeball well, greatly improve the quality of patient's life.
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Neoplasias do Seio Maxilar/cirurgia , Órbita/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Neoplasias do Seio Maxilar/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemAssuntos
Eletrocardiografia , Deficiência Intelectual , Síndrome do QT Longo , Mutação , Acetiltransferase N-Terminal A , Acetiltransferase N-Terminal E , Humanos , Síndrome do QT Longo/genética , Síndrome do QT Longo/diagnóstico , Deficiência Intelectual/genética , Criança , Acetiltransferase N-Terminal E/genética , Acetiltransferase N-Terminal A/genética , Masculino , Propranolol/uso terapêutico , Éxons , Heterozigoto , FemininoRESUMO
Objective: To summarize the clinical features and genetic analysis results of 10 children with Dent disease. Methods: The clinical data and gene test results of 10 boys aged from 8 months to 12 years with Dent disease diagnosed in Children's Hospital of Nanjing Medical University from January 2014 to July 2017 were analyzed retrospectively. Results: All patients had insidious onset, 5 cases were found to have proteinuria on routine urine examination after hospitalization duo to other diseases, 4 cases were admitted to hospital because increased foams in the urine, and 1 case was found to have proteinuria on health checkup. All cases presented with low molecular weight proteinuria, urine protein electrophoresis showed that the proportion of low molecular weight protein was greater than 50%, 7 cases had nephrotic-range proteinuria, but none had hypoproteinemia. Six cases had hypercalciuria, 3 cases had nephrocalcinosis, 1 case had nephrolithiasis, 2 cases had glomerular microscopic hematuria, in 1 case urine glucose wa weakly positive but blood glucose was normal. All patients had normal renal function, normal serum calcium, no hypophosphoremia and none had rickets. Genetic analysis results showed that 7 patients with variants in the CLCN5 gene, including 2 nonsense variants (p.R637X, p.Y143X), 3 missense variants (p.A540D, p.G135E, p.G703V), 1 deletion variant (exons 9, 10, 11, 12, 13, 1 missing), and 1 frameshift variant (p.T260Tfs*10). Three cases had missense variants of OCRL gene (p.I274T, p.I371T, p.F399S). Except for p.R637X and p.I274T, the other 8 cases had newly discovered variants. Five patients underwent a renal biopsy, the biopsy revealed focal global glomerulosclerosis in 3 patients, mild mesangial proliferative glomerulonephritis in 1 patient and renal minimal change in 1 patient. Mild focal tubular atrophy and interstitial fibrosis were noted in three cases. Mild segmental foot process effacement was noted under electron microscope in all five cases. Conclusions: All the children with Dent disease had insidious onset, low molecular weight proteinuria is the main clinical manifestation, most cases presented with nephrotic-range proteinuria, but there was no hypoalbuminemia, some cases were not associated with hypercalciuria. The pathogenic genes in most cases were CLCN5 and a few were OCRL. The types of genetic variation include missense variant, nonsense variant, deletion variant and frameshift variant. Although Dent disease is a renal tubular disease, renal biopsy suggests that most cases are associated with glomerular lesions.
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Doença de Dent/genética , Variação Genética , Hipercalciúria/etiologia , Biópsia , Criança , Pré-Escolar , Doença de Dent/complicações , Éxons , Testes Genéticos , Glomerulosclerose Segmentar e Focal/etiologia , Hematúria , Humanos , Lactente , Rim , Glomérulos Renais , Masculino , Mutação , Nefrocalcinose , Proteinúria/etiologia , Estudos Retrospectivos , RaquitismoRESUMO
Objective: To explore the positive rate of intrinsic factor antibody (IFAb) and level of vitamin B(12) (VitB(12)) in normal physical examination population and the possible relation between IFAb, VitB12 and sex, age, number of RBC, HGB and MCV. Methods: A total of 1 427 people who came to Peking Union Medical Colleague Hospital (PUMCH) for physical examination were enrolled. There were 758 males with average age of (52.5±14.5) years-old and 669 females with average age of (50.3±14.3) year-old. Beckman DxI800 automatic biochemical-immune analyzer and corollary reagents were used to analyze the level of serum IFAb and VitB(12). The results in different sex, age were documented and their correlation with the value of whole blood cell count was tested later on. Results: Among the 1 427 normal subjects, 66 (4.63%) were positive for IFAb. The positive rate for IFAb in the population≥40 years-old was higher than those<40 years-old (5.66% vs 1.48%, χ(2)=7.46, P=0.006). The deficiency rate of VitB(12) in the population<40 years-old, 40-59 years-old and ≥60 years-old was 2.22%, 2.51% and 5.50%, respectively (χ(2)=8.55, P=0.014). There were no difference between people with different sex in the positive rate of IFAb (5.15% for males and 4.04% for females, χ(2)=0.99, P=0.320) or in the deficiency rate of VitB(1)2 (3.83% for males and 2.69% for females, χ(2)=1.44, P=0.230). The results of multiple linear regression showed that HGB level of IFAb positive subjects was 3.05 g/L lower on average than those of IFAb negative, but IFAb had no effect on both RBC and MCV. There was no correlation between VitB(1)2 deficiency and HGB, RBC and MCV. Conclusion: The positive rate of IFAb and deficiency rate of VitB(1)2 increase as age increases. But the presence of VitB(12) deficiency is later than the positive findings of IFAb. IFAb showed some effects on the level of HGB, which may compensate the limitations of VitB(12) detection to some extent. It is necessary to check the IFAb and level of VitB(12) in people with middle or old ages.