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Objective: To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED). Methods: The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis. Results: Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177-GNAS, AIM1-FGFR3, and EPHA6-ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis (Pï¼0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone (P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone (Pï¼0.05). Conclusions: Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.
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Adenocarcinoma , Neoplasias Gástricas , alfa-Fetoproteínas , Humanos , Masculino , alfa-Fetoproteínas/metabolismo , Feminino , Pessoa de Meia-Idade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Idoso , Adulto , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/sangue , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Diferenciação Celular , Mutação , Fator de Transcrição CDX2/metabolismo , Fator de Transcrição CDX2/genética , GlipicanasRESUMO
A newly developed wearable balance diagnosis and treatment system was studied to evaluate the indexes of the abnormal balance function in patients with vestibular vertigo. A cross-sectional study was carried out. A total of 30 patients diagnosed with non-acute vestibular vertigo in the outpatient department of Eye, Ear, Nose and Throat Hospital Affiliated to Fudan University from July 2022 to May 2023 were selected as the vertigo group, including 13 males and 17 females, and aged (45.7±13.9) years. Meanwhile, 20 healthy controls (8 males and 12 females) were included as the control group, with a mean age of (43.6±8.0) years. The static balance and limits of stability (LOS) function of all subjects were assessed with wearable balance diagnosis and treatment system developed under the leadership of Eye & ENT Hospital of Fudan University. In the static balance test, the ratio of eyes open with cushions to eyes open without cushions in the vertigo group was less than that of the control group[1.20% (0.92%, 1.53%) vs 1.49% (1.22%, 1.81%), P=0.008], indicating that patients with non-acute vestibular vertigo may compensate static balance ability earlier. In vertigo group, the directional control in 8 directions, the maximum excursion in anterior, posterior, right anterior and right posterior directions, the endpoint excursion in the posterior, right posterior, and left posterior directions were all smaller than those of the control group (all P<0.05). The reaction time in the left posterior direction of vertigo group was longer than that of the control group (all P<0.05). Those results indicated that the directional control, maximum excursion and endpoint excursion of LOS could be considered as important reference indexes for dynamic balance function.
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Vertigem , Dispositivos Eletrônicos Vestíveis , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Estudos Transversais , Vertigem/diagnóstico , Vertigem/terapia , Pacientes Ambulatoriais , Equilíbrio PosturalRESUMO
Objectives: To investigate the mutation of PIK3CA in colorectal cancer and to analyze their clinicopathological features, and evaluate their role in clinical treatment and prognostication. Methods: A total of 128 paraffin-embbeded tissue samples of colorectal cancer from Shanxi Cancer Hospital from 2018 to 2021 were collected. DNA was extracted from the samples, and next-generation sequencing (NGS) was used to detect PIK3CA mutation. The relationship between PIK3CA mutation, their clinicopathological features, and prognosis were analyzed. Results: Among the 128 colorectal cancer samples, there were 75 males and 53 females; with aged range 32-86 years, median 61.5 years, 27 (21.09%) had PIK3CA mutations. Colorectal cancer with PIK3CA mutation was more likely to occur in male patients (P=0.007), which was related to tumor site (P=0.032), tumor size (P=0.029) and TP53 wild-type (P=0.001). The common site mutations of PIK3CA mostly occurred in tumors with tumor mutation burden≥10 Muts/Mb (P=0.031).PIK3CA mutation had no significant effect on the survival prognosis of patients, but the efficacy of anti-angiogenic therapy was poor in these patients. Conclusions: PIK3CA mutation is a common mutation in colorectal cancer and plays an important role in the occurrence and development of colorectal cancer. PIK3CA mutation may lead to resistance to anti-angiogenic drugs in colorectal cancer, but its impact on survival and prognosis to patients needs further study.
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Classe I de Fosfatidilinositol 3-Quinases , Neoplasias Colorretais , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Humanos , Classe I de Fosfatidilinositol 3-Quinases/genética , Masculino , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Pessoa de Meia-Idade , Idoso , Prognóstico , Adulto , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêuticoRESUMO
Objective: To explore the differences in metabolites and metabolic pathways in the aqueous humor between patients with presenile cataracts and senile cataracts. Methods: This metabolomic study was conducted at Tianjin Medical University Eye Hospital from August 2020 to September 2022. Eight patients with presenile cataracts (8 eyes) and 8 patients with senile cataracts (9 eyes) were included. Data were collected, including age, gender, preoperative uncorrected visual acuity, intraocular pressure, lens dysfunction index, and axial length. Aqueous humor and anterior capsule tissue samples were obtained during cataract surgery. Metabolites in the aqueous humor were detected using Liquid Chromatography-Mass Spectrometry in a non-targeted approach. The principal component analysis, differential analysis, clustering analysis, and correlation analysis were performed to identify differentially expressed metabolites. These metabolites were ranked based on the fold change (FC). The receiver operating characteristic (ROC) curve analysis and metabolic enrichment analysis were used to identify differential pathways and potential biomarkers for presenile cataracts. Immunohistochemistry was conducted on anterior capsule tissues, and pyruvate levels were measured by colorimetry to validate metabolomic results. Results: Patients with presenile cataracts included 7 males and 1 female, with a mean age of (37.50±4.90) years. Patients with senile cataracts were 7 males and 1 female, with a mean age of (73.44±5.22) years. Except for age, there were no significant differences in baseline data (P>0.05). A total of 347 differential metabolites were identified, 10 of which were potential biomarkers for presenile cataract according to the ROC curve analysis (all P<0.05), including propoxycaine (log2FC=7.26), 2-methyl-2, 3, 4, 5-tetrahydro-1, 5-benzodiazepine-4-ketone (log2FC=6.35), l-pyroglutamic acid (log2FC=-1.72), leanly-proline (log2FC=-0.77), and choline (log2FC=-0.56) in the positive ion mode, and N-phenylacetyl glutamine (log2FC=-1.84), pyruvate (log2FC=1.07), ascorbic acid (log2FC=0.92), pseudouracil nucleoside (log2FC=-0.68), and palmitic acid (log2FC=-0.51) in the negative ion mode. The metabolic enrichment analysis identified 72 differential pathways (32 cationic and 40 anionic), with significant differences in glutathione metabolism, cysteine and methionine metabolism, glycolysis or gluconeogenesis, pyruvate metabolism, and the citric acid cycle (P<0.05). The experimental validation showed reduced lactate dehydrogenase and increased pyruvate levels in patients with presenile cataracts (P<0.05). Conclusions: Pyruvate and nine other metabolites may serve as potential biomarkers for presenile cataracts. Pathways involving glutathione metabolism, cysteine and methionine metabolism, glycolysis or gluconeogenesis, pyruvate metabolism, and the citric acid cycle are notably dysregulated in patients with presenile cataracts.
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Humor Aquoso , Catarata , Metabolômica , Humanos , Catarata/metabolismo , Humor Aquoso/metabolismo , Metabolômica/métodos , Biomarcadores/metabolismo , Masculino , FemininoRESUMO
Objective: To analyze the clinic features of isolated myeloid sarcoma (IMS) involving the pleural cavity. Methods: A case of pleural isolated myeloid sarcoma (PIMS) with pleural effusion as the first manifestation was described. The related cases in literatures were reviewed with"myeloid sarcoma"and"pleural effusions"as the keywords to search China HowNet, Wanfang database and PubMed database. Results: A 59-year-old man complained of right chest pain for 2 months and worsening pain with distress and shortness of breath for 2 weeks. The chest CT scan showed pleural effusion on the right side. Flow cytometric analysis of pleural fluid showed that a population of blasts with CD34 expressing was 37.6% of the total nucleated cells. The pleural biopsy through medical thoracoscopy indicated lymphoproliferative lesions by pathological examination. Immunohistochemistry was performed on pleural histological sections and cell blocks of pleural effusions, which showed CD34 and CD117 positive expression. The diagnosis of PIMS was finally made. Two literature papers with 2 complete cases were found and reviewed. The 3 cases were analyzed. There were 2 males and 1 female. The age was 59, 51, 56 years respectively. One case was a patient with 3 weeks of right upper quadrant and epigastric pain, nausea, and weight loss. Cytological examination of the pleural fluid showed numerous poorly differentiated malignant cells. Histology from an open laparotomy in duodenal biopsies, gallbladder, and mesenteric lymph nodes supported the diagnosis of IMS. The other case was a patient with 6 weeks of dyspnea and a large swelling in the upper vestibular region. Thoracentesis showed 82% myeloid blasts in the pleural fluid. A gingival biopsy showed a diffuse infiltration by cells with a blastic appearance and supported IMS. Conclusion: PIMS was a very rare cause of pleural effusions. The cytological and histopathological evidences were useful to diagnose IMS involving the pleural cavity.
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Dor no Peito/etiologia , Dispneia/etiologia , Derrame Pleural/patologia , Sarcoma Mieloide/diagnóstico , Dor no Peito/diagnóstico por imagem , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pleura , Sarcoma Mieloide/patologia , ToracoscopiaRESUMO
Objective: To assess the efficacy and safety of tocilizumab and cyclophosphamide in patients with Takayasu arteritis (TA). Methods: Twenty-seven TA patients treated with tocilizumab (TCZ group) and 22 treated with cyclophosphamide (CTX group) were enrolled and retrospectively analyzed. The duration of treatment was 6 months. Disease activity and side effects were compared between the two groups. Results: After treatment, the median C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and disease activity scores in TCZ group were significantly lower than those in CTX group respectively [ESR 3 mm/1h vs. 8 mm/1h; CRP 0.13 mg/L vs. 1.09 mg/L; National Institutes of Health (NIH) score 0(0,1) vs. 0(1,1); the Indian Takayasu clinical activity score (ITAS 2010) 0(0,2) vs. 2(0,3.5), and the Indian Takayasu activity score with the acute phase response (ITAS-A) 0(0,2) vs. 2.5(0,3.5); all P<0.05]. The daily prednisone doses before treatment and after treatment in TCZ group were significantly lower than those in CTX group [(20.1±15.9) mg/d vs. (39.3±16.7) mg/d;(5.1±4.2)mg/d vs. (12.1±4.6) mg/d,both P<0.05)].The incidence of drug-related side effects in TCZ group was significantly lower than that in CTX group, which was 22.2% vs. 54.5% (P<0.05). Conclusion: Compared with CTX treatment, TCZ treatment for TA with less prednisone has better efficacy and safety.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Ciclofosfamida/uso terapêutico , Arterite de Takayasu/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Ciclofosfamida/administração & dosagem , Humanos , Estudos Retrospectivos , Arterite de Takayasu/patologia , Resultado do TratamentoRESUMO
A retrospective case control study was conducted in the Peking Union Medical College Hospital. Medical records were reviewed for demographic data, clinical features, laboratory results, systemic lupus erythematosus (SLE) disease activity evaluations, and ophthalmic examinations to investigate the clinical characteristics and significance of retinal vasculopathy (RV) in Chinese patients with systemic lupus erythematosus. The prevalence of RV was approximately 0.66% (35/5298) in SLE patients. A total of 60 eyes were involved. The ocular presentations included decrease of visual acuity (48/60, 80%), visual field loss (7/60, 11.7%), and diplopia (3/60, 5%). Ophthalmic fundoscopic examination revealed cotton-wool spots (30/60, 50%), retinal vascular attenuation (31/60, 51.6%), and hemorrhages (41/60, 68.3%). Retinal angiogram showed that 72.7% (16/22) eyes had vaso-occlusion. The ophthalmic episodes could occur at any stage of SLE duration, with a median of 12 months (0-168 months) following SLE onset. Twenty-one (35%) eyes did not recover, or even worsened, during hospital stay. RV was found to be significantly associated with neuropsychiatric lesions (51.4% vs. 21.3%, p = .005) and hematological disturbance (62.9% vs. 34.3%, p = .005). SLE patients with RV had significantly higher SLE disease activity index scores than controls (19.9 ± 0.9 vs. 10.2 ± 0.7, p < .001). An inverse association of anti-SSA antibody with RV was detected (34.3% vs. 67.1%, p = .001). Nervous system disturbance (odds ratio (OR) = 4.340, 95% confidence interval (CI) 1.438, 13.094, p = .009) and leukocytopenia (OR = 6.385, 95% CI 1.916, 21.278, p = .003) were independent risk factors, while anti-SSA antibody positivity (OR = 0.249, 95% CI 0.087, 0.710, p = .009) was a protective factor for RV in SLE patients. In certain cases, RV is a threatening condition for SLE patients presenting with clinical ocular manifestations. Ophthalmo-fundoscopic detection is recommended as soon as SLE is diagnosed.
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Lúpus Eritematoso Sistêmico/epidemiologia , Doenças Retinianas/epidemiologia , Doenças Vasculares/epidemiologia , Adolescente , Adulto , Distribuição de Qui-Quadrado , Criança , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prevalência , Fatores de Proteção , Recuperação de Função Fisiológica , Doenças Retinianas/diagnóstico , Doenças Retinianas/fisiopatologia , Doenças Retinianas/terapia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Doenças Vasculares/diagnóstico , Doenças Vasculares/fisiopatologia , Doenças Vasculares/terapia , Acuidade Visual , Campos Visuais , Adulto JovemRESUMO
Mechanotransduction is one of the processes by which cells sense and convert mechanical stimuli into biological signals. Experimental data from various species have revealed crucial roles for mechanotransduction in organ development and a plethora of physiological activities. Piezo proteins have recently been identified as the long-sought-after mechanically activated cation channels in eukaryotes. The architecture of mouse Piezo1 (mPiezo1) channel determined by cryoelectron microscopic single-particle analysis at medium resolution yielded important insights into the mechanical force sensing mechanism. mPiezo1 is found to form a trimeric propeller-like structure with the extracellular domains resembling three distal blades and a central cap. The transmembrane region consists of a central pore module that likely determines the ion-conducting properties of mPiezo1, and three peripheral wings formed by arrays of paired transmembrane helices. Compared with the central pore module, the three distal blades display considerably larger flexibility. In the intracellular region, three long beam-like domains (â¼80Å in length) support the whole transmembrane region and connect the mobile peripheral regions to the central pore module. This unique design suggests that the trimeric mPiezo1 may mechanistically function in similar principles as how propellers sense and transduce force to control the ion conductivity. This review summarizes the current knowledge on the structure and proposes possible gating mechanisms of mPiezo1.
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Canais Iônicos/química , Canais Iônicos/metabolismo , Animais , Fenômenos Biomecânicos , Membrana Celular/metabolismo , Humanos , Ativação do Canal IônicoRESUMO
Objective: To compare the diagnosis and treatment experience of brain abscesses and improve prognosis. Methods: The data of 302 patients of brain abscess at Department of Neurosurgery in Tianjin Medical University General Hospital from 1980 to 2014 was analyzed retrospectively. There were 215 male and 87 female patients aged from 11 to 82 years with mean age of (30±8) years. The patients was divided into 1980-2001 group and 2002-2014 group according to different diagnosis and the treatment methods. The therapy methods include operation and conservative treatment. There were 196 cases received operation, including 95 cases of excision, 89 cases of ventriculopuncture, 12 cases of excision after ventriculopuncture, 106 cases received drug conservative therapy. Two groups of information including clinical manifestation, abscess location, therapeutic effect and prognosis were compared by χ(2) test. Results: Compared to 1980-2001 group, adjacent infection incidence declined(χ(2)=8.000, P=0.005). The ratio of single abscess declined and multiple abscess increased(χ(2)=11.060, P=0.001), the infection proportion of frontal lobe and temporal lobe decreased(χ(2)=9.080, P=0.003; χ(2)=15.440, P=0.000). The ratio of headache and vomit and papilledema declined significantly(χ(2)=23.290, P=0.000; χ(2)=21.020, P=0.000; χ(2)=2.290, P=0.001). Total mortality of 302 patients were 23 cases and 5 cases of 1980-2001 group and 2002-2014 group (10.4% vs. 6.3%, χ(2)=1.180, P=0.277). However, there were statistical difference in postoperative mortality between both groups (14.4% vs. 4.0%, χ(2) =3.880, P=0.049). Conclusion: With the application of antibiotics and the development of neurosurgical techniques, the prognosis of brain abscess has been improved.
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Abscesso Encefálico/cirurgia , Procedimentos Neurocirúrgicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Lobo Temporal , Adulto JovemRESUMO
OBJECTIVE: To analysis the clinical features of cardiovascular involvement in Behcet's disease. METHODS: We reviewed 35 medical records of Behcet's disease with cardiovascular lesions in Anzhen Hospital, Capital Medical University from January 2002 to January 2014. 77.1% patients (27/35) were male. The mean (x±s) age when cardiovascular diseases occur was 37.19±10.4 years in male and 36.0±8.6 years in female respectively. RESULTS: The clinical spectrum of cardiovascular abnormalities included valvular regurgitation (20, 57.1%), conduction system disturbances (10, 28.6%), intracardiac thrombosis(1, 2.9%), aneurysms of the arteries (13, 37.1%), artery stenosis or occlusion (5, 14.3%), pulmonary vascular diseases(3, 8.6%), venous thrombosis(4, 11.4%). Twenty patients had more than one of these lesions. Inflammatory indicators had no significantly difference between the above subgroups (P>0.05). Treatments included corticosteroids and immunosuppressive drugs, together with symptomatic treatments, intervention therapy and operation.Two inpatient died from multiple organ dysfunction syndrome and cardiac shock respectively. CONCLUSIONS: Cardiovascular involvement is a remarkable systemic lesion of Behcet's disease. Multi-subject cooperation is beneficial for the diagnosis and treatment of the disease.
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Aneurisma/diagnóstico , Síndrome de Behçet/complicações , Doenças Cardiovasculares/etiologia , Trombose/diagnóstico , Corticosteroides/uso terapêutico , Adulto , Aneurisma/cirurgia , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/cirurgia , Síndrome de Behçet/terapia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/terapia , Terapia Combinada , Feminino , Doenças das Valvas Cardíacas , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Trombose Venosa/diagnóstico , Trombose Venosa/etiologiaRESUMO
OBJECTIVE: To investigate the clinical features of valvular lesions in Takayasu's arteritis. METHODS: We analyzed 22 medical records of patients with Takayasu's arteritis and valvular lesions in Anzhen Hospital, Capital Medical University from January 2012 to January 2015. RESULTS: The spectrums of valvular involvements were aortic valve regurgitation (11, 50%), aortic valve stenosis (1, 4.5%), mitral valve regurgitation (1, 4.5%), mitral valve stenosis (1, 4.5%) and multiple valvular diseases (7, 36.5%).64.7% of patients with aortic valve regurgitation had aortic root dilation.Heart failure was the most common manifestation (63.6%). Glucocorticoid and/or immunosuppressant were administrated on 11 (50%) patients.One (4.5%) patient received Tocilizumab injection.Surgeries were performed on 12 (54.5%) patients with cardiac architecture.Reversible changes in cardiac structure were found by echocardiography within one week after surgery (P<0.05). Three patients died during 10-46 month follow-up, with none of whom taking any anti-inflammatory treatments. CONCLUSIONS: Aortic regurgitation is the prominent valvular lesion in Takayasu's arteritis, mostly secondary to aortic root dilation.Operation could block myocardium reconstruction promptly.The early surgical complication is rare, while perivalvular leakage may occur during longstanding follow-up.Poor inflammatory control might lead to poor long-term outcome.
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Insuficiência da Valva Aórtica , Arterite de Takayasu , Estenose da Valva Aórtica , Ecocardiografia , Humanos , Insuficiência da Valva MitralRESUMO
Objective: To investigate the significance of CXCL12/CXCR4 expression in T lymphoblastic lymphoma/leukemia (T-LBL/ALL) and its prognostic significance. Methods: Using immunohistochemical EnVision method, CXCL12, CXCR4 and Ki-67 expression were evaluated in 72 cases of T-LBL/ALL and 30 selected cases of lymph node reactive hyperplasia (LH) as control. In addition, CXCL12 and CXCR4 mRNA expression levels were examined by real-time reverse transcription polymerase chain reaction (real-time RT-PCR) method. Results: Immunohistochemical results showed that the expression rates of CXCL12 and CXCR4 in T-LBL/ALL were 84.7%(61/72) and 91.6%(66/72), respectively, and these were not different from the expression in the LH control group. The expression indexes of Ki-67 <80% and ≥80% were 25 cases (34.7%, 25/72) and 47 cases (65.3%, 47/72), respectively. Real-time quantitative PCR demonstrated that CXCL12 and CXCR4 mRNA expression in T-LBL/ALL was 62.4% and 71.5%, respectively, and was statistically different (P<0.05) from that of the control group. Single factor analysis found that CXCL12 mRNA expression in T-LBL/ALL was positively correlated with Ann Arbor staging and KPS score (P<0.05); CXCL12 protein expression was positively correlated with splenomegaly (P<0.05); CXCR4 mRNA expression was positively correlated with the IPI score, clinical symptoms, mediastinal widening and bone marrow involvement (P<0.05); CXCR4 protein expression was positively correlated with mediastinal widening (P<0.05); CXCL12 mRNA expression was positively correlated with CXCL12 protein and CXCR4 protein expression (P<0.05), but not the CXCR4 mRNA and protein levels. There was no correlation between CXCL12 and CXCR4 protein expression and CXCR4 mRNA expression. Multivariate COX regression analysis showed that high expression of CXCR4 protein, hepatosplenomegaly and bone marrow involvement were risk factors for T-LBL/ALL outcome. Conclusions: CXCL12/CXCR4 expression is associated with disease progress, mediastinal widening, bone marrow involvement and adverse outcome in T-LBL/ALL. CXCL12/CXCR4 axis plays an essential role in the occurrence and development of T-LBL/ALL. However, CXCL12 and CXCR4 protein expression are not entirely reflected by mRNA transcription levels, and there may be other molecules involved in CXCL12/CXCR4 expression and regulation. With CXCR4 antagonists undergoing clinical trials, targeting the CXCL12/CXCR4 axis may be a promising treatment strategy for T-LBL/ALL.
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Quimiocina CXCL12/metabolismo , Linfoma de Células T/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Receptores CXCR4/metabolismo , Humanos , Linfoma de Células T/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Few studies have examined the genes related to risk fac-tors that may contribute to intracranial aneurysms (IAs). This study in Chinese patients aimed to explore the relationship between IA and 28 gene loci, proven to be associated with risk factors for IA. We recruited 119 patients with aneurysms and 257 controls. Single factor and logistic regression models were used to analyze the association of IA and IA rup-ture with risk factors. Twenty-eight single nucleotide polymorphisms (SNPs) in 22 genes were genotyped for the patient and control groups. SNP genotypes and allele frequencies were analyzed by the chi-square test. Logistic regression analysis identified hypertension as a factor that increased IA risk (P = 1.0 x 10(-4); OR, 2.500; 95%CI, 1.573-3.972); IA was associated with two SNPs in the TSLC2A9 gene: rs7660895 (P = 0.007; OR, 1.541; 95%CI, 1.126-2.110); and in the TOX gene: rs11777927 (P = 0.013; OR, 1.511; 95%CI, 1.088-2.098). Subsequent removal of the influence of family relationship identified between 12 of 119 patients enhanced the significant association of these SNPs with IA (P = 0.001; OR, 1.691; 95%CI, 1.226-2.332; and P = 0.006; OR, 1.587; 95%CI, 1.137-2.213 for rs7660895 and rs11777927, respectively). Fur-thermore, the minor allele of rs7660895 (A) was also associated with IA rupture (P = 0.007; OR, 2.196; 95%CI, 1.230-3.921). Therefore, hypertension is an independent risk factor for IA. Importantly, the TSL-C2A9 (rs7660895) and TOX (rs11777927) gene polymorphisms may be associated with formation of IAs, and rs7660895 may be associated with IA rupture.
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Aneurisma Roto/genética , Proteínas Facilitadoras de Transporte de Glucose/genética , Proteínas de Grupo de Alta Mobilidade/genética , Hipertensão/genética , Aneurisma Intracraniano/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Aneurisma Roto/etnologia , Aneurisma Roto/patologia , Povo Asiático , Estudos de Casos e Controles , Feminino , Expressão Gênica , Frequência do Gene , Loci Gênicos , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Proteínas de Grupo de Alta Mobilidade/metabolismo , Humanos , Hipertensão/etnologia , Hipertensão/patologia , Aneurisma Intracraniano/etnologia , Aneurisma Intracraniano/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
The geometric and electronic properties of silicene paired with a MoS2 substrate are studied systematically by using density functional theory with van der Waals corrections. It is found that the nearly linear band dispersions can be preserved in the heterobilayers due to the weak interface interactions. Meanwhile, the band gap is opened because of the sublattice symmetry broken by the intrinsic interface dipole. Moreover, the band gap values could be effectively modulated under an external electric field. Therefore, a way is paved for silicene-MoS2 heterobilayers to be candidate materials for logic circuits and photonic devices.
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BACKGROUND: This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating patients with leptomeningeal metastases (LM) from non-small-cell lung cancer (NSCLC) who progressed from epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment in an expanded, prospective, single-arm, phase II clinical study (ChiCTR1800016615). PATIENTS AND METHODS: Patients with confirmed NSCLC-LM who progressed from TKI received IP (50 mg, day 1/day 5 for 1 week, then every 3 weeks for four cycles, and then once monthly) until disease progression or intolerance. Objectives were to assess overall survival (OS), response rate, and safety. Measurable lesions were assessed by investigator according to RECIST version 1.1. LM were assessed according to the Response Assessment in Neuro-Oncology (RANO) criteria. RESULTS: The study included 132 patients; 68% were female and median age was 52 years (31-74 years). The median OS was 12 months (95% confidence interval 10.4-13.6 months), RANO-assessed response rate was 80.3% (106/132), and the most common adverse event was myelosuppression (n = 42; 31.8%), which reversed after symptomatic treatment. The results of subgroup analysis showed that absence of brain parenchymal metastasis, good Eastern Cooperative Oncology Group score, good response to IP treatment, negative cytology after treatment, and patients without neck/back pain/difficult defecation had longer survival. Gender, age, previous intrathecal methotrexate/cytarabine, and whole-brain radiotherapy had no significant influence on OS. CONCLUSIONS: This study further showed that IP is an effective and safe treatment method for the EGFR-TKI-failed NSCLC-LM, and should be recommended for these patients in clinical practice and guidelines.
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Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Injeções Espinhais , Neoplasias Pulmonares , Pemetrexede , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Pemetrexede/uso terapêutico , Pemetrexede/farmacologia , Pemetrexede/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Adulto , Receptores ErbB/antagonistas & inibidores , Estudos Prospectivos , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/secundário , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/efeitos adversos , Carcinomatose Meníngea/tratamento farmacológico , Carcinomatose Meníngea/secundário , Resultado do TratamentoRESUMO
We enrolled and reviewed 26 medical records of systemic lupus erythematosus (SLE) with intracranial hemorrhage (cases) and 104 randomly matched records of SLE without intracranial hemorrhage (controls) out of 6653 admitted patients at Peking Union Medical College Hospital from 1994 to 2012, to analyze the clinical characteristics and risk factors of intracranial hemorrhage in SLE. The incidence of SLE with intracranial hemorrhage was only 0.39% within the last 18 years at Peking Union Medical College Hospital. However, the in-hospital fatality rate was quite high (23.1%). Headache was the most common symptom (53.5%) in SLE patients with intracranial hemorrhage. The anatomical localization of the hemorrhages in the brain was predominantly located in the cerebrum. Intracranial hemorrhage could happen in either stable or active SLE patients. SLE patients with intracranial hemorrhage presented other neuropsychiatric syndromes defined by the American College of Rheumatology (ACR) in 1999, thrombocytopenia and antiphospholipid syndrome more frequently than controls. Thrombocytopenia was the independent risk factor for intracranial hemorrhage coexisting with SLE (OR=3.687, 95% CI 1.510-9.001, p=0.004).
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Hemorragias Intracranianas/etiologia , Lúpus Eritematoso Sistêmico/complicações , Adolescente , Adulto , Estudos de Casos e Controles , China/epidemiologia , Feminino , Células Hep G2 , Humanos , Hemorragias Intracranianas/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Personalized ventilation (PV) system in conjunction with total ventilation system can provide cleaner inhaled air for the user. Concerns still exist about whether the normally protecting PV device, on the other hand, facilitates the dispersion of infectious agents generated by its user. In this article, two types of PV systems with upward supplied fresh air, namely a chair-based PV and one kind of desk-mounted PV systems, when combined with mixing ventilation (MV) and displacement ventilation (DV) systems, are investigated using simulation method with regard to their impacts on co-occupant's exposure to the exhaled droplet nuclei generated by the infected PV user. Simulation results of tracer gas and particles with aerodynamic diameter of 1, 5, and 10 µm from exhaled air show that, when only the infected person uses a PV, the different PV air supplying directions present very different impacts on the co-occupant's intake under DV, while no apparent differences can be observed under MV. The findings demonstrate that better inhaled air quality can always be achieved under DV when the adopted PV system can deliver conditioned fresh air in the same direction with the mainly upward airflow patterns of DV.
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Poluição do Ar em Ambientes Fechados/análise , Transmissão de Doença Infecciosa , Ventilação/instrumentação , Humanos , Temperatura , Ventilação/métodosRESUMO
OBJECTIVE: To investigate the correlation of subclinical human papillomavirus (HPV) infection (SPI) with genital warts and cervical erosion. MATERIALS AND METHODS: The questionnaire was firstly conducted in experimental groups (genital warts + cervical erosion), and then cervical liquid-based cytology was performed, followed by colposcopy and pathological diagnosis. In the control group, cervical liquid-based cytology and pathological diagnosis were performed. Hybrid Capture 2 assay (HC2) was conducted to detect the cervical high-risk HPV DNA. RESULTS: The positive rate of cervical SPI in experimental groups were significantly higher than control group (p < 0.01), and in the genital warts group it was significantly higher than cervical erosion group (p < 0.05). There was no significant difference of SPI positive rate for cervical erosion with different area and degree (p > 0.05). Compared to control group, the detection rates of cervical high-risk HPV DNA in the experimental groups significantly increased (p < 0.01), and the difference between vulvar condyloma and cervical erosion groups was not statistically significant (p < 0.05). The detection rate of high-risk HPV DNA in positive SPI cases was significantly higher than negative SPI cases. CONCLUSIONS: Women with genital warts and cervical erosion are high-risk individuals for cervical cancer, and deserve a focused initial and follow-up management.
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Condiloma Acuminado/complicações , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/etiologia , Adolescente , Adulto , DNA Viral/análise , Feminino , HumanosRESUMO
OBJECTIVE: Esophageal adenocarcinoma is known to have a high incidence and poor prognosis in the population and is a serious threat to public health. As a precancerous lesion of esophageal adenocarcinoma, early intervention of Barrett's esophagus is key to the prevention and treatment of esophageal adenocarcinoma. MATERIALS AND METHODS: Research publications on Barrett's esophagus (BE) were searched in the Web of Science Core Collection, and the extracted publications were screened to obtain relevant data. The included articles were analyzed bibliometrically using Microsoft Excel 2019, Citespace V, and VOSviewer 1.6.18. The keywords used for the search can be categorized into 4 clusters: endoscopic therapy, clinical screening, risk factors, and drug therapy. RESULTS: A total of 3,497 publications from 83 countries and 3,319 research institutions were retrieved. Since 1983, there has been a rapid increase in publications in this field. The United States (n = 1,941) and Mayo Clinic (n = 218) were the most productive countries and institutions, respectively, and the most prominent author was Kenneth K. Wang, who published 89 papers. CONCLUSIONS: In this study, we were able to perform a comprehensive and systematic analysis of literature related to BE. Endoscopic resection and radiofrequency ablation may emerge as research hotspots for BE in the future. Our findings provide insight into the current trends in the management of BE and facilitate the choice of appropriate measures to improve the prognosis of patients.