RESUMO
A total of 82 patients and healthy subjects in the First Affiliated Hospital of Sun Yat-sen University from March to August 2023 were recruited. The cohort consisted of 43 patients with head and neck squamous cell carcinoma (HNSCC) and 39 non-cancer patients or healthy subjects. There were 63 males and 19 females, with a median age of 62 (46, 67) years. The levels of folate receptor-positive circulating tumor cells (FR+CTCs) in the blood of HNSCC patients and non-cancer/healthy subjects were 12.4 (8.5, 17.8) floate unit (FU)/3 ml and 5.0 (3.8, 6.6) FU/3 ml, respectively, with a statistically significant difference (P<0.001). The area under the receiver operating characteristic (ROC) curve for FR+CTCs levels was 0.937 (95%CI: 0.888-0.986, P<0.001), with a cut-off value of 7.4 FU/3 ml determined by the maximum Youden index. At this cut-off value, the sensitivity and specificity of FR+CTCs for diagnosing HNSCC were 90.70% and 89.74%, respectively. The current study suggests that FR+CTCs could be used as a liquid biopsy marker for the screening and diagnosis of HNSCC.
Assuntos
Neoplasias de Cabeça e Pescoço , Células Neoplásicas Circulantes , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Feminino , Masculino , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/metabolismo , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/sangue , Idoso , Sensibilidade e Especificidade , Biomarcadores Tumorais/sangue , Curva ROC , Receptores de Folato com Âncoras de GPI/metabolismo , Receptores de Folato com Âncoras de GPI/sangueRESUMO
Objective: To investigate the safety and efficacy of haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) conditioning with the same dosage form of antithymoglobulin (ATG) in patients with severe aplastic anemia (SAA) failure to ATG. Methods: This was a retrospective cohort study. A total of 65 patients with SAA who failed ATG treatment and received haplo-HSCT conditioning with the same dosage of ATG at the Institute of Hematology, Peking University People's Hospital between July 2008 and October 2020 were included as the ATG treatment failure group. An additional 65 SAA patients who applied ATG for the first time during haplo-HSCT were randomly selected by stratified sampling as the first-line haplo-HSCT group. Baseline clinical data and follow-up data of the two groups were collected. Conditioning-related toxicity within 10 days after ATG application and long-term prognosis were analyzed. The Kaplan-Meier was used to calculate the overall survival rate, and the Log-rank test was applied to compare the rates of the two groups. Results: In the ATG treatment failure group, there were 36 males and 29 females, and the age at the time of transplantation [M (Q1, Q3)] was 16 (8, 25) years. In the first-line haplo-HSCT group, there were 35 males and 30 females, with a median age of 17 (7, 26) years. Within 10 days of ATG application, the incidence of noninfectious fever, noninfectious diarrhea, and liver injury in the ATG treatment failure group was 78% (51 cases), 45% (29 cases), and 28% (18 cases), respectively, and in the first-line haplo-HSCT group was 74% (48 cases), 54% (35 cases), and 25% (16 cases), respectively; the difference between the two groups was not statistically significant for any of these three parameters (all P>0.05). For graft-versus-host disease (GVHD), there was no significant difference between the ATG treatment failure group and the first-line haplo-HSCT group in the development of 100 day â ¡ to â £ acute GVHD (29.51%±0.35% vs. 25.42%±0.33%), â ¢ to â £ acute GVHD (6.56%±0.10% vs. 6.78%±0.11%), and 3-year chronic GVHD (26.73%±0.36% vs. 21.15%±0.30%) (all P>0.05). Three-year overall survival (79.6%±5.1% vs. 84.6%±4.5%) and 3-year failure-free survival (79.6%±5.1% vs. 81.5%±4.8%) were also comparable between these two groups (both P>0.05). Conclusions: Compared with no exposure to ATG before HSCT, similar early adverse effects and comparable survival outcomes were achieved in patients with SAA who failed previous ATG treatment and received haplo-HSCT conditioning with the same dosage form of ATG. This might indicate that previous failure of ATG treatment does not significantly impact the efficacy and safety of salvaging haplo-HSCT in patients with SAA.
RESUMO
Protein phosphatase 4 (PPP4) is a protein phosphatase that, although highly expressed in the testis, currently has an unclear physiological role in this tissue. Here, we show that deletion of PPP4 catalytic subunit gene Ppp4c in the mouse causes male-specific infertility. Loss of PPP4C, when assessed by light microscopy, did not obviously affect many aspects of the morphology of spermatogenesis, including acrosome formation, nuclear condensation and elongation, mitochondrial sheaths arrangement and '9 + 2' flagellar structure assembly. However, the PPP4C mutant had sperm tail bending defects (head-bent-back), low sperm count, poor sperm motility and had cytoplasmic remnants attached to the middle piece of the tail. The cytoplasmic remnants were further investigated by transmission electron microscopy to reveal that a defect in cytoplasm removal appeared to play a significant role in the observed spermiogenesis failure and resulting male infertility. A lack of PPP4 during spermatogenesis causes defects that are reminiscent of oligoasthenoteratospermia (OAT), which is a common cause of male infertility in humans. Like the lack of functional PPP4 in the mouse model, OAT is characterized by abnormal sperm morphology, low sperm count and poor sperm motility. Although the causes of OAT are probably heterogeneous, including mutation of various genes and environmentally induced defects, the detailed molecular mechanism(s) has remained unclear. Our discovery that the PPP4C-deficient mouse model shares features with human OAT might offer a useful model for further studies of this currently poorly understood disorder.
Assuntos
Infertilidade Masculina/genética , Fosfoproteínas Fosfatases/deficiência , Cauda do Espermatozoide/patologia , Animais , Feminino , Fertilização , Fertilização in vitro , Infertilidade Masculina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Fosfoproteínas Fosfatases/metabolismo , Contagem de Espermatozoides , Motilidade dos Espermatozoides/genética , Cauda do Espermatozoide/metabolismo , Espermatogênese/genéticaRESUMO
Objective: To investigate the clinical indicators for preoperative prediction of impacted ureteral stones and analyze the predictive value of ureteral wall area(UWA). Methods: A total of 197 patients who underwent ureteroscopic lithotripsy due to ureteral stones at our institution from January to December 2020 were retrospectively analyzed. Preoperative patient age, gender, body mass index (BMI), history of hypertension, diabetes mellitus, side of stone, location of stone, maximum diameter of stone, CT value of stone, C-reactive protein (CRP), creatinine, renal pelvis diameter, ureteral wall thickness and UWA were collected. Patients were divided into impacted and non-impacted groups according to whether the stones were impacted intraoperatively. Univariate analysis was used to compare the differences in each clinical indicator between the two groups, and multivariate logistic regression was performed to analyze the independent predictors of impacted stones for those with differences. The receiver operating characteristic (ROC) curve was used to analyze the predictive power of each independent predictor, and the Delong test was used to analyze whether the difference in the area under the curve (AUC) of each independent predictor was statistically significant. Results: All 197 patients successfully completed the operation, aged 51 (36, 56) years; 137 males and 60 females. According to the results of ureteroscopy, they were divided into 82 cases of impacted ureteral stones and 115 cases of non-impacted ureteral stones. Univariate analysis showed that there were significant differences in maximum stone diameter, stone CT value, renal pelvis diameter, ureteral wall thickness and ureteral wall area between the two groups (P<0.05); There was no significant difference in age, gender, BMI, history of hypertension, diabetes, stone side, location of stone, CRP and creatinine (P>0.05). Multivariate logistic regression analysis showed that stone CT value (P<0.01), ureteral wall thickness (P<0.001) and ureteral wall area were independent predictors of impacted ureteral stones (P<0.001). The ROC curve was used to compare the predictive efficacy of independent predictors of stone CT value, ureteral wall thickness and ureteral wall area. The area under the ureteral wall area curve was the largest (AUC = 0.901, 95%CI: 0.859-0.943, P<0.001), followed by ureteral wall thickness (AUC = 0.799, 95%CI: 0.736-0.862, P<0.001) and stone CT value (AUC = 0.700, 95%CI: 0.626-0.775, P<0.001). By Delong test, there were significant differences in AUC between ureteral wall area and stone CT value (Z=4.527, P<0.001) and ureteral wall thickness (Z=3.407, P<0.001). The best predictive value of ureteral wall area was 79.6 mm2. The sensitivity and specificity of this critical value for predicting ureteral incarcerated calculi were 80.1% and 89.5%. Conclusions: The UWA, ureteral wall thickness as well as the CT value of stones were all independent predictors of impacted ureteral stones, and UWA had a better predictive value.
Assuntos
Litotripsia , Ureter , Cálculos Ureterais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Cálculos Ureterais/terapia , UreteroscopiaRESUMO
To explore the epidemiological characteristics, trends and relevant factors of pre-hospital mortality due to acute myocardial infarction (AMI) from 1999 to 2016 in Tianjin city, based on mortality surveillance information and household registration population information. Standardized mortality rates were calculated using the year 2000 world standard population. From 1999 to 2016, the research result showed that the pre-hospital crude mortality rates of AMI were 39.47/100 000 to 90.64/100 000 and the standardized mortality rates were 30.92/100 000 to 53.90/100 000. The proportion of pre-hospital AMI deaths was 73.96%-81.92% (t=1.09, P>0.05) within the same period. Aged, female, rural residents, unmarried, divorced, widowed, low education level, and outdoor workers have a relative higher proportion of pre-hospital AMI mortality.
Assuntos
Infarto do Miocárdio/mortalidade , Idoso , China/epidemiologia , Cidades , Feminino , Humanos , Masculino , Mortalidade/tendências , Fatores SocioeconômicosRESUMO
From 1999 to 2015, there were 6 186 cases of leukemia deaths in tianjin residents, the males accounted for 58.28% (3 605) and 52.31% (3 236) deaths lived in urban areas; the crude mortality rate of Leukemia increased from 3.47/100 000 to 4.28/100 000 [t=7.09, P<0.001, annual percent change (APC)=1.30%] and the standardized mortality rate decreased from 3.15/100 000 to 3.01/100 000 (t=-2.95, P=0.006, APC=-0.65%). Special attention should be focused on children, the elderly, males and rural residents.
Assuntos
Leucemia/mortalidade , Idoso , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Mortalidade/tendências , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricosRESUMO
Objective: To explore the trends and distribution of intracerebral hemorrhage (ICH) mortality of the residents with different characteristics from 1999 to 2015 in Tianjin. Methods: ICH mortality data in 1999-2015 were from Tianjin population based mortality surveillance system. The mortality rate of ICH, difference in the rate by gender, age, and geographic distribution, and trends over the years were analyzed. Standardized mortality rates of ICH were calculated using the year 2000 world standard population. Joinpoint regression and Cochran-Armitage trend were used to examine the trends in mortality. Results: A total of 102 279 ICH death cases were observed in Tianjin from year 1999 to 2015. The crude ICH mortality rate in Tianjin decreased from 76.35/100 000 in 1999 to 51.46/100 000 in 2015 (annual percent change (APC)=-1.96%, Z=-31.08, P<0.001) , and the standardized mortality rate decreased from 72.41/100 000 to 29.00/100 000 (APC=-5.20%, Z=-70.91, P<0.001). The crude mortality rate of ICH mortality in males decreased from 87.26/100 000 to 59.89/100 000 (APC=-1.79%, Z=-21.71, P<0.001) and the standardized mortality rate decreased from 85.65/100 000 to 35.75/100 000 (APC=-4.93%, Z=-52.32, P<0.001). The crude mortality rate of ICH mortality in females decreased from 65.21/100 000 to 42.98/100 000 (APC=-2.18%, Z=-22.28, P<0.001) and the standardized mortality rate decreased from 59.17/100 000 to 22.26/100 000 (APC=-5.63%, Z=-48.15, P<0.001). The ICH mortality rate under 35 years old increased from 0.78/100 000 to 0.92/100 000 (APC=4.41%, Z=5.07, P<0.001), especially in males increasing from 0.90/100 000 to 1.54/100 000 (APC=6.59%, Z=6.52, P<0.001). The crude mortality rate of ICH in urban areas decreased from 69.74/100 000 to 41.79/100 000 (APC=-3.18%, Z=-31.43, P<0.001) and the standardized mortality rate decreased from 57.56/100 000 to 20.42/100 000 (APC=-6.59%, Z=-53.43, P<0.001). The crude mortality rate of ICH in rural areas decreased from 82.99/100 000 to 61.49/100 000 (APC=-1.10%, Z=-14.06, P<0.001) and the standardized mortality rate decreased from 91.55/100 000 to 43.14/100 000 (APC=-3.78%, Z=-43.21, P<0.001). The ICH mortality rate in rural areas was higher than that in urban areas (P<0.05). Conclusion: ICH mortality rate in Tianjin decreased from 1999 to 2015. Further efforts to reduce ICH mortality in Tianjin is needed, in particular males, under 35 years old, and people in rural areas.
Assuntos
Hemorragia Cerebral/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Vigilância da População , Padrões de Referência , População RuralRESUMO
Objective: To explore the trends and distribution of chronic obstructive pulmonary disease (COPD) mortality of the residents with different characteristics from 2000 to 2016 in Tianjin. Methods: COPD mortality data in 2000-2016 were from Tianjin population based mortality surveillance system. The mortality rate of COPD, difference in the rate by gender, age, and geographic distribution, and the trend over years were analyzed. Age-sex-standardized mortality rates of COPD were calculated using the year 2000 world standard population. Joinpoint regression and Cochran-Armitage trend analysis were used to examine the trend of mortality. Results: The crude COPD mortality rate in Tianjin decreased from 57.57/100 000 in 2000 to 28.23/100 000 in 2016 (annual percent change (APC)=-5.01%, Z=-64.76, P<0.001), and the standardized mortality rate decreased from 56.53/100 000 in 2000 to13.88/100 000 in 2016 (APC=-9.17%, Z=-100.83, P<0.001). The crude COPD mortality rate of males decreased from 54.57/100 000 to 27.77/100 000 (APC=-4.89%, Z=-43.63, P<0.001) and the standardized mortality rate decreased from 57.52/100 000 to 14.63/100 000 (APC=-9.07%, Z=-71.48, P<0.001). The crude COPD mortality rate of females decreased from 60.63/100 000 to 28.68/100 000 (APC=-5.12%, Z=-47.92, P<0.001) and the standardized mortality rate decreased from 55.53/100 000 to 13 13/100 000 (APC=-9.27%, Z=-71.13, P<0.001). The crude mortality rate of COPD in urban areas decreased from 45.07/100 000 to 19.54/100 000 (APC=-5.35%, Z=-42.38, P<0.001) and the standardized mortality rate decreased from 39.24/100 000 to 7.45/100 000 (Z=-63.97, P<0.001, APC=-10.22%). The crude mortality rate of COPD in rural areas decreased from 70.20/100 000 to 37.24/100 000 (APC=-4.77%, Z=-48.77, P<0.001) and the standardized mortality rate decreased from 78.88/100 000 to 25.70/100 000 (APC=-7.59%, Z=-72.43, P<0.001). The COPD mortality rate in rural areas was higher than that in urban areas (P<0.001). The COPD mortality rate in 35 years old and over decreased from 2000 to 2016 (P<0.001). Conclusion: The COPD mortality in Tianjin decreased from 2000 to 2016. More efforts are need to reduce COPD mortality in Tianjin, in particular people in rural areas.
Assuntos
Disparidades nos Níveis de Saúde , Vigilância da População , Doença Pulmonar Obstrutiva Crônica/mortalidade , Adulto , Distribuição por Idade , China/epidemiologia , Feminino , Humanos , Masculino , População Rural/estatística & dados numéricos , Distribuição por Sexo , População Urbana/estatística & dados numéricosRESUMO
Objective: To study clinical and genetic characteristics of a Leber hereditary optic neuropathy (LHON) family with the heteroplasmic m.14484T>C mutation. Methods: A cross-sectional study. The objects of the study included a 31-year-old male LHON patient with the heteroplasmic m.14484T>C mutation (the proband) who visited Department of Ophthalmology in the Affiliated Central Hospital of Qingdao University in March 2015 and other 36 matrilineal relatives in a four-generation family (12 males and 24 females aged 2-81 years, median 27 years). The visual acuity, intraocular pressure, fundus, color vision, visual field, visual evoked potential and optical coherence tomography were evaluated in maternal members. The mitochondrial DNA (mtDNA) sequence of fragments including m.14484 loci was detected by Sanger sequencing in 33 members. The sequencing peaks were analyzed by QSVanalyzer software to get the heteroplasmy levels of m.14484T>C mutation. The mtDNA of the proband was amplified by PCR and sequenced. Assembled sequence of mtDNA was compared with the updated consensus Cambridge sequence. The differences in visual evoked potential, optical coherence tomography and heteroplasmy levels were compared between two groups by the t-test, and among multiple groups by the single factor variance analysis. Results: Among the 33 maternal members of the family, 4 patients, 28 carriers and 1 person without a mutation were confirmed. The penetrance was 12.5% (4/32) . In addition to 4 patients with obvious abnormality on the ophthalmic examination, 5 carriers also appeared anomaly on the electrophysiological and visual function examinations. Compared to carriers, the amplitude of P100 was obviously decreased in the LHON patients[ (5.6±2.6) µV vs. (15.6±9.6) µV, t=2.880, P=0.006]. Significantly reduced values were seen in the average retinal nerve fiber layer thickness[ (71±17) µm vs. (99±11) µm, t=5.969, P< 0.001], in each side of the sub-area macular thickness, and in the nasal side of the lateral sub-area macular thickness [ (260±16) µm vs. (291±12) µm, t=5.593, P<0.001] between the LHON patients and carriers. The heteroplasmic levels were 80%±3% in the LHON patients, and 27%±18% in the unaffected members;the difference was significant (t=-8.395, P<0.001). The average degree of heteroplasmy had no difference between male and female members (48%±34% vs. 35%±28%, t=-1.147, P=0.258). The average mutation load was 29%±14% in the second generation members, 36%±29% in the third generation members, and 51%±36% in the fourth generation members;the differences were not statistically significant (F=1.152, P=0.330). The difference in the heteroplasmic levels was not statistically significant between mothers and their offspring (31%±25% vs. 42%±32%, t=1.165, P=0.251). Compared to Cambridge consensus sequence, 41 mutations was found in mtDNA of the proband, of which, 10 were missense mutations, including mutations m.4216T>C and m.3394T>C. According to the phylogenetic tree, the haplotype of the proband was M9a (M9a1a1c1a). Conclusions: In the family with the heteroplasmic m.14484T>C mutation, clinical manifestations of LHON appear in the individuals whose heteroplasmic level is more than 75%, and all of patients show typical chronic optic atrophy on the ophthalmic examination. The carriers with the m.14484T>C mutation also appear anomaly on the electrophysiological and visual function examinations. The heteroplasmic level of m.14484T>C mutation has a tendency to increase during the transmission in the family. The primary mutation m.14484T>C coordinate mutations m.4216T>C and m.3394T>C to increase the penetrance and incidence of abnormal visual function in carriers. (Chin J Ophthalmol, 2018, 54: 526-534).
Assuntos
DNA Mitocondrial , Mutação , Atrofia Óptica Hereditária de Leber , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Potenciais Evocados Visuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia Óptica Hereditária de Leber/genética , Atrofia Óptica Hereditária de Leber/fisiopatologia , Linhagem , Filogenia , Adulto JovemRESUMO
Objective: To explore the trends and distribution of cerebral infarction between sexes, ages and urban-rural areas from 1999 to 2015 in Tianjin, China, and provide data for targeted prevention and control strategies of cerebral infarction in Tianjin. Methods: Cerebral infarction mortality data from January 1, 1999 to December 31, 2015 were obtained from Tianjin population based mortality surveillance system established by the Tianjin Centers for Disease Control and Prevention, and population data of permanent residents were obtained from Tianjin Municipal Public Security Bureau. The trends change and affecting factors including gender, age, and geographic distribution on mortality following cerebral infarction were analyzed. Results: (1) Cerebral infarction mortality rate in Tianjin increased from 1999 to 2015 with the crude mortality rate of 57.06/100 000 to 105.22/100 000 (Z=59.65, P<0.01, annual percent change(APC)=3.39%) and decreased with the standardized mortality rate from 55.59/100 000 to 56.12/100 000 (Z=-5.47, P<0.01, APC=-0.35%). (2) The crude mortality rate (64.23/100 000 to 118.72/100 000) and standardized mortality rate (65.44/100 000 to 67.23/100 000) of male cerebral infarction was higher than that of female (crude: 49.73/100 000 to 91.64/1/100 000, standardized: 45.73/100 000 to 45.01/100 000) from 1999 to 2015. (3) With the increase of age, the mortality of cerebral infarction increased gradually from 1999 to 2015 (all Z>0.00,all P<0.01). (4) The mortality rate of cerebral infarction in urban areas increased with the crude mortality rate from 71.43/100 000 to 103.20/100 000 (Z=17.34, P<0.01, APC=1.30%) and decreased with the standardized mortality rate from 61.04/100 000 to 43.77/100 000 (Z=-32.49, P<0.01, APC=-3.06%) from 1999 to 2015. The mortality rate of cerebral infarction in rural areas increased with the crude mortality rate from 42.63/100 000 to 107.32/100 000 (Z=69.14, P<0.01, APC=5.95%) and with the standardized mortality rate from 48.34/100 000 to 77.09/100 000 (Z=36.88, P<0.01, APC=5.95%) from 1999 to 2015. Conclusions: Cerebral infarction crude mortality increased and standardized mortality decreased from 1999 to 2015 in Tianjin. Further efforts to reduce cerebral infarction mortality in Tianjin are needed, special attention should be focused on the elderly, male and rural residents.
Assuntos
Infarto Cerebral/mortalidade , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Médicos , Padrões de Referência , População Rural , População UrbanaRESUMO
SATB2-associated syndrome (SAS) is a multisystemic disorder caused by alterations of the SATB2 gene. We describe the phenotype and genotype of 12 individuals with 10 unique (de novo in 11 of 11 tested) pathogenic variants (1 splice site, 5 frameshift, 3 nonsense, and 2 missense) in SATB2 and review all cases reported in the published literature caused by point alterations thus far. In the cohort here described, developmental delay (DD) with severe speech compromise, facial dysmorphism, and dental anomalies were present in all cases. We also present the third case of tibial bowing in an individual who, just as in the previous 2 individuals in the literature, also had a truncating pathogenic variant of SATB2. We explore early genotype-phenotype correlations and reaffirm the main clinical features of this recognizable syndrome: universal DD with severe speech impediment, mild facial dysmorphism, and high frequency of craniofacial anomalies, behavioral issues, and brain neuroradiographic changes. As the recently proposed surveillance guidelines for individuals with SAS are adopted by providers, further delineation of the frequency and impact of other phenotypic traits will become available. Similarly, as new cases of SAS are identified, further exploration of genotype-phenotype correlations will be possible.
Assuntos
Anormalidades Craniofaciais/genética , Deficiências do Desenvolvimento/genética , Deficiência Intelectual/genética , Proteínas de Ligação à Região de Interação com a Matriz/genética , Fatores de Transcrição/genética , Adolescente , Criança , Pré-Escolar , Anormalidades Craniofaciais/fisiopatologia , Deficiências do Desenvolvimento/fisiopatologia , Exoma/genética , Feminino , Mutação da Fase de Leitura , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Deficiência Intelectual/fisiopatologia , Masculino , FenótipoRESUMO
The Janus kinase-signal transducers and activators of transcription signaling pathway (JAK/STAT pathway) have displayed a critical role in tumor development and progression in multiple malignancies. Previous studies showed that inhibition of JAK/STAT signaling blocked cell growth and metastasis in cancer cells, however, the antitumor effects of JAK inhibitor AG490 on gallbladder cancer (GBC) have not been reported. Our present study aimed to investigate the effects and associated mechanisms of JAK inhibitor AG490 on cell growth, invasive potential and apoptosis in GBC cells (GBC-SD and SGC-996) indicated by MTT, cell colony formation, Transwell and flow cytometry. As a consequence, we found that JAK2 inhibitor AG490 inhibited cell growth and invasion, and induced cell apoptosis and cycle arrest in GBC-SD and SGC-996 cells. Furthermore, the expression levels of p-JAK2, p-STAT3, VEGFC-/-D and cyclinD1 were downregulated, while p53 expression was upregulated in AG490-treated GBC cells indicated by Western blot assay. Therefore, our findings demonstrate that JAK inhibitor AG490 inhibits growth and invasion of GBC cells via blockade of JAK2/STAT3 signaling and provides the potential therapeutic strategy for the treatment of GBC patients.
Assuntos
Antineoplásicos/farmacologia , Células Epiteliais/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Janus Quinase 2/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Tirfostinas/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclina D1/antagonistas & inibidores , Ciclina D1/genética , Ciclina D1/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Vesícula Biliar/efeitos dos fármacos , Vesícula Biliar/metabolismo , Vesícula Biliar/patologia , Humanos , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/agonistas , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Fator C de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator C de Crescimento do Endotélio Vascular/genética , Fator C de Crescimento do Endotélio Vascular/metabolismo , Fator D de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator D de Crescimento do Endotélio Vascular/genética , Fator D de Crescimento do Endotélio Vascular/metabolismoRESUMO
Neuroblastoma is the most common extracranial solid tumor in childhood which often acquires drug resistance and becomes aggressive phenotypes. The high-risk patients suffer from high mortality due to the limitation of the treatment strategies. ARID1A (AT-rich interactive domain-containing protein 1A), a subunit of SWI/SNF complexes, is considered as a tumor suppressor in many cancers. The aim of the present study was to investigate the effect of ARID1A on migration and invasion in neuroblastoma cells. The shRNA targeting ARID1A was designed and delivered into SK-N-SH cells to knock down ARID1A expression. Knockdown of ARID1A by shRNA significantly increased the viability and invasion ability, and caused G1 arrest inhibition and DNA synthesis increase in SK-N-SH cells. Moreover, Knockdown of ARID1A increased the activity and expression of matrix metalloproteinase (MMP)-2 and -9 in SK-N-SH cells. Furthermore, ARID1A knockdown caused diminished expression of E-cadherin, enhanced expression of N-cadherin and ß-catenin nuclear translocation in SK-N-SH cells. These results suggest that loss of ARID1A may associate with the promotion of invasion and metastasis of neuroblastoma. Our findings indicate ARID1A is a tumor suppressor in neuroblastoma.
Assuntos
Movimento Celular , Invasividade Neoplásica , Neuroblastoma/patologia , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Caderinas/metabolismo , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proteínas de Ligação a DNA , Técnicas de Silenciamento de Genes , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neuroblastoma/genética , RNA Interferente Pequeno , beta Catenina/metabolismoRESUMO
Objective: To observe the incidence of acute myocardial infarction (AMI) between 1999 and 2013 in Tianjin residents and analyze the incidence differences on residents with various age, gender and living in urban or rural areas. The data might help for targeted prevention strategies among Tianjin residents. Methods: AMI incidence data between 1999 and 2013 were obtained based on Tianjin cardiovascular disease incidence surveillance registry established by the Tianjin Centers for Disease Control and Prevention (CDC). Related information such as permanent residents' population data were obtained from Tianjin Municipal Public Security Bureau. The Chinese population data in 2000 were used for age-sex-standardized rates estimation. Difference between two (or more) independent groups was compared by the Chi Square statistics. The Chi-square test for trend was used for computing the incidence trend in years and ages. Results: AMI incidence rate in Tianjin declined from the year 1999 to 2013 with the rude incidence rate of 80.46/100 000 to 81.29/100 000, and with the standardized incidence rate of 64.85/100 000 to 44.57/100 000 (Z=-35.767, P<0.001). AMI incidence decreased gradually in residents aged over 45 years old (P<0.01), but increased in residents younger than 45 years old (P<0.001) from 1999 to 2013. The AMI incidence rate is consistently higher in male residents (rude incidence 99.89/100 000-102.98/100 000, standardized incidence rate 78.53/100 000-56.61/100 000) than in female residents (rude incidence 61.18/100 000-59.44/100 000, standardized incidence rate 50.31/100 000-31.76/100 000, both P<0.001) and higher in urban residents (rude incidence rate 133.98/100 000-98.02/100 000, standardized incidence rate 99.89/100 000-50.12/100 000) than in rural residents (rude incidence rate 35.57/100 000-66.19/100 000, standardized incidence rate 32.68/100 000-43.51/100 000, Z=6.217, P<0.001). AMI incidence decreased significantly in the urban residents (rude incidence rate 133.98/100 000-98.02/100 000, standardized incidence rate 99.89/100 000-50.12/100 000, Z=-46.968, P<0.001), while significantly increased in rural residents (rude incidence rate 35.57/100 000-66.19/100 000, standardized incidence rate 32.68/100 000-43.51/100 000, Z=6.217, P<0.001) during the study period. Conclusions: The general incidence of AMI decreased during the study period in Tianjin residents. However, AMI incidence significantly increased in young male residents and rural residents. It is necessary to develop corresponding strategies for AMI control for Tianjin residents with different age/gender and living in different areas.
Assuntos
Infarto do Miocárdio/epidemiologia , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , População RuralRESUMO
Objective: To explore the trends change in mortality following acute myocardial infarction (AMI) from 1999 to 2015 in Tianjin, China. Methods: AMI mortality data from 1999 to 2015 were obtained from Tianjin population based mortality surveillance system operated by the Tianjin Centers for Disease Control and Prevention (CDC), and population data of permanent residents were obtained from Tianjin Municipal Public Security Bureau. The trends change and affecting factors including gender, age, and geographic distribution on mortality following AMI were analyzed. Results: (1)The standardized mortality rate of AMI in Tianjin from 1999 to 2015 was 52.32/100 000 to 48.62/100 000. Adjusted AMI mortality rate from 1999 to 2013 was 52.32/100 000 to 73.72/100 000, indicating an increased trend(Z=32.15, P<0.001)with an annual percent change (APC) of 2.53%. Adjusted AMI mortality rate was decreased from 2013 to 2015: 73.72/100 000 to 48.62/100 000 (Z=-22.80, P<0.001), and APC was -19.07%. Above trends change was similar for male and female residents (all P<0.001). (2)The AMI standardized mortality rate of male was significantly higher than that of female during the 17 years. The AMI standardized mortality of male was significantly higher than that of female in<35, 35-44, 45-54, 55-64 and ≥65 years old group, respectively. AMI mortality rate increased with age. (3)Except in the year of 2002 and 2003, the AMI mortality rate were significantly higher in rural residents than in urban residents during this study period (P<0.001). Adjusted AMI mortality in urban residents increased from 1999 to 2009(Z=8.05, P<0.001, APC=1.43%), and decreased in the year from 2009 to 2015 (Z=-18.71, P<0.001, APC=-6.32%). Adjusted AMI mortality in rural residents increased in the year of 1999 to 2013(Z=56.05, P<0.001, APC=5.84%), and decreased in the year of 2013 to 2015 (Z=-24.40, P<0.001, APC=-21.35%). Conclusions: Our results suggest that AMI mortality in Tianjin increased from 1999 to 2013, and decreased from 2013 to 2015, and male and rural residents have higher AMI mortality. Related prevention and intervention measures should be taken to decrease AMI mortality, especially for male and rural residents.
Assuntos
Infarto do Miocárdio/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População RuralRESUMO
Target leaf spot is a sorghum leaf disease caused by Bipolaris sorghicola, a species of fungus with a global distribution. In this study, we investigated the process by which B. sorghicola invades cells of barley, onion, Arabidopsis thaliana species, and sorghum. The results showed that within 8 h of coming into contact with host cells, the hyphal ends of B. sorghicola expand and form a uniform infective penetration pegbolt-like structure; a primary infection mycelium can be formed inside host cells within 24 h after contact, which can infect closed cells after 48 h. A mycelium can grow within the gap between cells and form infective hyphae. The pathogen infection process was the same in different host cells. B. sorghicola can affect root cells through soil infection, indicating that it may also have characteristics of soil-borne pathogens.
Assuntos
Ascomicetos/fisiologia , Interações Hospedeiro-Patógeno , Raízes de Plantas/microbiologia , Arabidopsis/microbiologia , Hordeum/microbiologia , Cebolas/microbiologia , Microbiologia do Solo , Sorghum/microbiologiaRESUMO
A serine/threonine protein kinase gene (NrSTK) was cloned from Nicotiana repanda based on the sequence of a previously isolated resistance gene analog (RGA). Expression of RGA was induced by challenge with the pathogen black shank. The NrSTK gene was predicted to encode a protein kinase that contained an ATP binding site at residues 41-69 and a serine/threonine protein kinase activation sequence spanning the region 161-173. Overexpression of NrSTK in the susceptible tobacco variety Honghuadajinyuan significantly enhanced resistance to black shank, indicating that NrSTK plays a role in incompatibility reactions between tobacco and the pathogen. Characterization of NrSTK will help elucidate the molecular mechanisms involved in black shank resistance in N. repanda.
Assuntos
Resistência à Doença/genética , Nicotiana/genética , Doenças das Plantas/genética , Proteínas Serina-Treonina Quinases/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , DNA Complementar , Dados de Sequência Molecular , Filogenia , Plantas Geneticamente Modificadas , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
The interleukin-18 (IL-18) gene -607 C/A polymorphism has been reported to be associated with gastrointestinal cancer, but there are conflicting results from previous studies on said topic. Therefore, the aim of this meta-analysis is to derive a more precise estimation of the association between the -607 C/A polymorphism in the IL-18 gene and gastrointestinal cancer risk. Literature searches of PubMed, Google Scholar, and Web of Science databases were carried out in 2015. Five studies were assessed with a total of 1618 cases and 1155 healthy controls. When results from all eligible studies were pooled into the meta-analysis, we found significant association between the IL-18 gene -607 C/A polymorphism and gastrointestinal cancer risk (CC vs AA: OR = 0.93, 95%CI = 0.72- 1.20; CC vs CA: OR = 0.76, 95%CI = 0.62-0.92; dominant model: OR = 1.25, 95%CI = 1.03-1.50; recessive model: OR = 1.09, 95%CI = 0.87-1.37). In the subgroup analysis, significant associations between the -607 C/A polymorphism and gastrointestinal cancer risk were found in esophageal cancer. However, this polymorphism did not appear to have any influence on gastric cancer and colorectal cancer susceptibility. In conclusion, this meta-analysis suggests that the -607 C/A polymorphism in the IL-18 gene may be associated with susceptibility to esophageal cancer. Further studies with large sample sizes are needed to confirm these conclusions.
Assuntos
Neoplasias Gastrointestinais/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Interleucina-18/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Alelos , Estudos de Casos e Controles , Genótipo , Humanos , Razão de Chances , Viés de PublicaçãoRESUMO
MicroRNA molecules have been increasingly regarded as a diagnostic and prognostic marker of certain diseases. The aim of this study was to investigate the expression and clinical significance of miR-122 and miR-29 in liver disease related to hepatitis B virus infection. The serum levels of miR-122 and miR-29 in 20 patients with hepatocellular carcinoma (HCC), 20 patients with liver cirrhosis (LC), 29 patients with chronic hepatitis B (CHB), 20 cases of hepatitis B virus carriers (ASC), and 20 healthy controls (HC) were determined by a fluorescence real-time quantitative PCR method and then evaluated by clinical correlation analysis. Compared with the serum levels of miR-122 in the HC, LC, and ASC groups, those in patients with HCC and CHB were significantly increased. The serum levels of miR-29 in LC patients were lower than those in the healthy controls (P < 0.01). A positive correlation was observed between the expression of miR-122 and miR-29, and HBV DNA in patients with CHB. A negative correlation was found between miR-29 and α-fetoprotein in patients with HCC. The elevation in miR-122 was correlated with liver damage in CHB patients and with the pathogenesis of liver cancer in HCC patients. The decrease in miR-29 expression was related to the incidence of liver fibrosis. The detection of miR-122 and miR-29 may be useful in evaluating the inflammatory liver injury and fibrosis associated with chronic HBV infection.
Assuntos
Carcinoma Hepatocelular/sangue , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/complicações , Neoplasias Hepáticas/sangue , MicroRNAs/sangue , Alanina Transaminase/sangue , Sequência de Bases , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Primers do DNA , DNA Viral/sangue , Vírus da Hepatite B/genética , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The development of hematology in China has gradually begun since the 1950s. After several generations of hard work, it has grown into a young but vibrant discipline. The development of Chinese hematology has experienced rapid rise and steady growth, but there is still a gap with the international level of hematology development. Only by constructing a Chinese community of hematology and forming a joint force to promote the development of hematology can we better realize the Chinese Dream in the field of hematology.