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Objective: Due to genetic factors might increase the risk of depression, this study investigated the genetic risk factors of depression in Chinese Han population by analyzing the association between 13 candidate genes and depression. Methods: 439 depression patients and 464 healthy controls were included in this case-control study. Case group consisted of 158 males and 281 females, aged (29.84±14.91) years old, who were hospitalized in three departments of the affiliated Brain Hospital of Guangzhou Medical University including Affective Disorders Department, Adult Psychiatry Department and Geriatrics Department, from February 2020 to September 2021. The control group consisted of 196 males and 268 females, aged (30.65±12.63) years old. 20 loci of 13 candidate genes in all subjects were detected by MALDI-TOF mass spectrometry. Age difference was compared using the student's t-test, the distributions of gender and genotype were analyzed with Pearson's Chi-square test. The analyses of Hardy-Weinberg equilibrium, allele frequency and the genetic association of depression were conducted using the corresponding programs in PLINK software. Results: PLINK analysis showed that SCN2A rs17183814, ABCB1 rs1045642, CYP2C19*3 rs4986893 and NAT2*5A rs1799929 were associated with depression before Bonferroni correction (χ2=10.340, P=0.001; χ2=11.010, P=0.001; χ2=9.781, P=0.002; χ2=4.481, P=0.034). The frequencies of minor alleles of above loci in the control group were 12.07%, 43.64%, 2.59% and 3.88%, respectively. The frequencies of minor alleles of loci mentioned above in the case group were 17.43%, 35.99%, 5.47% and 6.04%, respectively. OR values were 1.538, 0.726, 2.178 and 1.592, respectively. After 1 000 000 permutation tests using Max(T) permutation procedure, the four loci were still statistically significant, the empirical P-value were 0.002, 0.001, 0.003 and 0.042, respectively. However, only three loci including SCN2A rs17183814, ABCB1 rs1045642 and CYP2C19 rs4986893 had statistical significance after Bonferroni correction, the adjusted P-value were 0.026, 0.018 and 0.035, respectively. Conclusion: SCN2A rs17183814, ABCB1 rs1045642 and CYP2C19*3 rs4986893 were associated with depression's susceptibility in Chinese Han population. The A allele of SCN2A rs17183814 and CYP2C19*3 rs4986893 were risk factors for depression, while the T allele of ABCB1 rs1045642 was a protective factor for depression.
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Subfamília B de Transportador de Cassetes de Ligação de ATP , Arilamina N-Acetiltransferase , Citocromo P-450 CYP2C19 , Transtorno Depressivo Maior , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Alelos , Arilamina N-Acetiltransferase/genética , Estudos de Casos e Controles , Clopidogrel , Citocromo P-450 CYP2C19/genética , Transtorno Depressivo Maior/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Canal de Sódio Disparado por Voltagem NAV1.2 , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
Objective: To compare the specific IgE positive rates of the patients between allergic respiratory diseases and respiratory infectious diseases in Guangzhou, the relationship between the co-sensitization of house dust mite (HDM) allergen and Aspergillus fumigatus (AF) allergen and asthma, allergic rhinitis with asthma, pneumonia, upper respiratory infections, bronchitis, serum total immunoglobulin E (total Immunoglobulin E, tIgE) and age were analyzed, to provide the basis for the prevention and treatment of respiratory allergic diseases and respiratory infectious diseases in this area. Methods: A total of 2 535 patients with confirmed respiratory allergic diseases and respiratory infectious diseases were selected retrospectively from the outpatient or inpatient department of the First Affiliated Hospital of Guangzhou Medical University from April 2017 to June 2021 and detected HDM and AF specific IgE (sIgE) by the ImmunoCAP system. The age range was 1 to 89 years. The median age was 5 years. The average age was 9. ≤3 years old group n=894, 4-6 years old group n=721, 7-18 years old group n=615, 19-49 years old group n=207, >49 years old group n=98. There were 1 596 males (62.96%) and 939 females (37.04%). There were 1 279 cases of allergic diseases and 1 256 cases of respiratory infectious diseases. The different disease groups were divided into asthma group (411 cases), allergic rhinitis group (458 cases), allergic rhinitis combined with asthma group (410 cases), pneumonia group (463 cases), upper respiratory tract infection group (299 cases) and bronchitis group (494 cases). The difference of specific IgE (sIgE) and tIgE between HDM and AF was analyzed. For statistical analysis, continuous variables were tested by Mann-Whitney U. Classification data by chi-square test or Fisher's exact test. Results: 1 313 (51.79%) patients were sIgE positive for HDM allergen, 65 (2.56%) were sIgE positive for AF allergen, and 50 (1.97%) were both positive. In the respiratory allergic disease group, 877 cases (68.57%,877/1 279) were positive for HDM allergen sIgE, 57 cases (4.46%,57/1 279) were positive for AF allergen sIgE, and 44 cases (3.44%,44/1 279) were both positive; 436 cases (34.71%,436/1 256) of respiratory infectious diseases were positive for HDM allergen sIgE, 8 cases (0.64%,8/1 256) were positive for AF allergen sIgE, and 6 cases (0.48%,6/1 256) were both positive. In monosensitization, the HDM allergen sIgE sensitization rate was the highest in the allergic rhinitis & asthma group, at 80.24% (329/410). The positive rate of HDM allergen sIgE in male patients was 53.76%(858/1 596), and the positive rate in female patients was 46.22%(434/939), and the difference between the two was statistically significant (χ2=13.449, P<0.001). In polysensitization, asthma patients (5.35%,22/411) had the highest positive rate of HDM sensitization with AF, followed by allergic rhinitis patients (3.06%,14/458), allergic rhinitis with asthma (1.95%,8/410). The positive rate of respiratory infectious diseases such as pneumonia (0.43%,2/463), upper respiratory infections (0.33%,1/299), and bronchitis (0.61%,3/494) with AF was extremely low. The positive rate of HDM combined with AF in infants(≤3 years old group,0.34%, 3/894; 4-6 years old group, 0.97%, 7/721)was significantly lower than that in teenagers and adults(7-18 years old group,3.58%, 22/615; 19-49 years old group,6.28%, 13/207;>49 years old group,5.10%, 5/98).In the patients with HDM and AF combined sensitization, HDM sIgE levels were distributed in all grades, and AF sIgE levels were mainly in grades 1, 2, and 3. Conclusion: The positive rate of HDM combined with AF was higher in patients with respiratory allergic diseases such as asthma, allergic rhinitis, and allergic rhinitis combined with asthma, suggesting that clinical attention should be paid to the combination of HDM and AF in patients with asthma and allergic rhinitis, especially adults, more likely to be combined with AF.
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Asma , Bronquite , Doenças Transmissíveis , Rinite Alérgica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alérgenos , Animais , Antígenos de Dermatophagoides , Aspergillus fumigatus , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina E , Lactente , Masculino , Pessoa de Meia-Idade , Pyroglyphidae , Estudos Retrospectivos , Adulto JovemRESUMO
Objective: This study was to investigate the perioperative safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP), and analyze the risk factors of serious adverse events (SAEs). Methods: The occurrences of perioperative SAEs were retrospectively analyzed in 254 PMP patients treated with CRS plus HIPEC. Univariate and multivariate analysis were performed to identify independent risk factors. Results: Among the 272 CRS plus HIPEC procedures for 254 PMP patients, a total of 93 (34.2%) perioperative SAEs occurred, including 26 in infection, 22 in digestive system, 17 in respiratory system, 15 in cardiovascular system, 8 in hematological system, and 4 in urinary system. In terms of severity, the vast majority was grade â ¢ with 76 cases, followed by grade â £ with 13 cases and grade â ¤ with 4 cases. Univariate analysis revealed 3 risk factors of perioperative SAEs: HIPEC regimen (P=0.020), intraoperative red blood cell transfusion volume (P=0.004), and intraoperative blood loss volume (P=0.002). Multivariate analysis by logistic regression model analysis revealed that intraoperative red blood cell transfusion volume was an independent risk factor for perioperative SAEs (OR=1.160, P=0.001). Conclusion: In conclusion, the perioperative safety of CRS plus HIPEC was acceptable. Moreover, intraoperative blood loss volume and red blood cell transfusion volume are expected to be reduced in order to prevent SAEs for PMP patients.
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Terapia Combinada/métodos , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/terapia , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the effect of tumor-stroma ratio (TSR) on disease progression and prognosis of pseudomyxoma peritonei (PMP) from the appendix. METHODS: The study included 30 PMP patients with complete individual patient data, who underwent cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in Beijing Shijitan Hospital. Image-Pro Plus was used to quantitatively analyze the proportion of tumor and stromal areas in hematoxylin-eosin staining pathological images, from which TSR was derived. Correlation studies were conducted to evaluate the relationships between TSR and clinicopathological features, immunohistochemical characteristics, and prognosis of PMP. RESULTS: Among 30 PMP patients, there were 16 males (53.3%) and 14 females (46.7%), with the mean age of (54.9±2.3) years. There were 15 cases (50.0%) of low-grade mucinous carcinoma peritonei (LMCP) and high-grade mucinous carcinoma peritonei (HMCP), respectively, with vascular tumor emboli occurring in 4 cases (13.3%), nerve invasion occurring in 3 cases (10.0%), and lymphatic metastasis occurring in 4 cases (13.3%). The median peritoneal cancer index (PCI) score was 36 (range: 3-39). The median TSR was 8% (range: 2%-24%), with TSR≤10% in 19 cases (63.3%) and TSR>10% in 11 cases (36.7%). Immunohistochemistry showed that 16 cases (53.3%) had Ki67 label index ≤ 50% and 14 cases (46.7%) > 50%. The mutation rate of p53 was 56.7% and the loss rate of MMR protein was 11.8%. In addition, the expression rates of MUC2, MUC5AC, CDX2, CK7, and CK20 were 66.7%, 100.0%, 82.6%, 56.0%, and 92.3%, respectively. There were significant correlations between TSR and histopathological types, nerve invasion, Ki67 label index, and p53 mutation (P<0.05 for all). At the end of the last follow-up, 21 patients (70.0%) died and 9 patients (30.0%) survived, including 6 patients survived with tumor. The median overall survival (OS) was 12.7 months (95%CI: 10.4-11.5 months), and the 1-, 2-, and 3-year survival rates were 60.5%, 32.3%, and 27.7%, respectively. The median OS was 19.4 months (95%CI: 3.0-35.9 months) in the TSR≤10% group, versus 12.6 months (95%CI: 0.7-24.5 months) in the TSR>10% group (χ2=3.996, P=0.046). CONCLUSION: TSR is correlated with histopathological types, tumor proliferation, invasion behaviors and prognosis of PMP, thus could be a new prognostic indicator for PMP.
Assuntos
Apêndice , Hipertermia Induzida , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
Objective: To establish patient derived xenograft (PDX) model of malignant peritoneal mesothelioma (MPM), and to identify the key characteristics of tumor biology of the model, so as to provide an experiment platform for studying the pathologic mechanisms and new therapeutic strategies for MPM. Methods: Surgically excised MPM tumor tissues were inoculated subcutaneously in BALB/c-nu/nu mice for 3 stable passages. In the 4th passage, the subcutaneous tumors were harvested under aseptic conditions, cleaned and made into MPM tumor cell homogenate. Four nude mice (two males and two females) were selected and one male and one female nude mouse were inoculated in the abdominal cavity at the dose of 100 µL, others were inoculated at a dose of 200 µL. The PDX model of MPM was established. The changes of body mass in nude mice were measured regularly, the extent of abdominal and pelvic tumors was judged by experimental peritoneal cancer index (ePCI) score, and the pathologic characteristics of tumors were analyzed. Results: The subcutaneous and abdominal animal models of MPM were successfully established. The subcutaneous tumor model grew into tumor on the 20th day, followed by a slow growth stage between the 20th and 29th day, then a rapid growth stage between the 30th and 57th day. According to the dose of tumor cells (100, 200 µL) and timing (14th and 69th days after grafting), the abdominal tumor model successfully simulated the early and late clinical stages of MPM. The HE staining results of the MPM nude mice model showed that the tumor was epithelial mesothelioma and invaded most of the organs, including liver, spleen, pancreas, mesentery. Immunohistochemical staining for calretinin, cytokeratin 5/6, WT1 and Ki-67 were positive. Whole-genome exon sequencing identified 26 and 36 high frequency gene mutations in tumors derived from the PDX model and clinical sample from patients, including 21 common gene mutations. Conclusions: The PDX model of MPM is established. The model is characterized by highly malignant tumor with rapid growth and high invasiveness.
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Neoplasias Pulmonares , Mesotelioma , Neoplasias Pleurais , Animais , Linhagem Celular Tumoral , Feminino , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos NusRESUMO
Objective: To analysis the clinical characteristics of"recurrence"RNA positive patients with Coronavirus disease 2019 ï¼COVID-19ï¼ and compared with those without"recurrence". Methods: 98 patients with COVID-19 in Wuhan Jinyintan Hospital and designated treatment hospitals in Quanzhou were included in this study from February 2020 to April 2020. There were 55 males and 43 femalesï¼ aged from15 to 83 yearsï¼ with a median age of 57.5 yearsï¼ in which 20 cases were complicated with basic diseases. 15 of these patients had been diagnosed and hospitalized had been found as"recurrence"2019-nCoV RNA positive after discharge while the other 83 cases were all negative. The clinical classification of all patients was common type. Clinical data of the COVID-19 RNA"recurrence"patients were collectedï¼ and general situationsï¼ symptomsï¼ laboratory examinations and CT images were also observed and analyzed. The patients were divided into 2019-nCoV"recurrent"group and 2019-nCoV"non-recurrent"group. There are 10 males and 5 females in 2019-nCoV"recurrent"group while 45 males and 38 females in"non-recurrent"group ï¼χ²=0.800ï¼P=0.371ï¼. The age of 2019-nCoV"recurrent"group ï¼57±21ï¼ was higher than that of"non-recurrent"groupï¼53±17ï¼. 8 of 15 the COVID-19"recurrent"group patients and 12 of 83"non-recurrent"patients have basic diseases. IgG and IgM of 2019-nCoVï¼ IL-6ï¼ procalcitoninï¼ ESRï¼ CRPï¼ BNP and other serum biochemical index levels were measured and compared between groups. Results: ï¼1ï¼ The proportion of patients with common type of COVID-19 was 15.3% during 2-week medical observation after discharge. ï¼2ï¼ All of the 2019-nCoV"recurrent"patients were hospitalized due to COVID-19 RNA positiveï¼ when they were quarantined after discharged from hospital. All the patients with mild symptoms which were clarified as common typeï¼ including 5 cases of feverï¼ 6 cases of coughï¼ 5 cases of expectorationï¼ and 2 cases of slight shortness of breath. The time of symptoms appeared on ï¼5.73±2.82ï¼ days after discharge. ï¼3ï¼ The serum procalcitonin of all 2019-nCoV"recurrent"group patients were normalï¼all<0.05 ng/mlï¼. The BNP of"recurrent"group ï¼151±171ï¼ ng/Lï¼ was higher than that of"non-recurrent"group ï¼63±78ï¼ ng/L ï¼t = 3.207ï¼ P = 0.000ï¼. There was no significant difference in laboratory tests like leukocyte ï¼»ï¼6.17±2.4ï¼ and ï¼6.04±2.41ï¼×109/Lï¼½ï¼ lymphocyteï¼»ï¼1.59±0.52ï¼ and ï¼1.32±0.64ï¼×109/Lï¼½ï¼ CRP ï¼»ï¼12.54±28.20ï¼ and ï¼21.74±25.63ï¼mg/Lï¼½ï¼ ESR ï¼»ï¼31.07±28.72ï¼ and ï¼34.10±22.16ï¼mm/1 hï¼½ï¼ AST ï¼»ï¼24.73±9.15ï¼ and ï¼30.24±23.20ï¼U/Lï¼½ï¼ ALT ï¼»ï¼22.60±12.82ï¼ and ï¼36.47±34.12ï¼U/Lï¼ï¼ LDH ï¼»ï¼268±208ï¼ and ï¼270±164ï¼U/Lï¼½ï¼ D-dimer ï¼»ï¼0.60±0.50ï¼ and ï¼0.84±0.98ï¼µg/Lï¼½ï¼ ferritin ï¼»ï¼294±195ï¼ and ï¼395±319ï¼µg/Lï¼½ï¼ IL-6 ï¼»ï¼9.17±6.42ï¼ and ï¼14.28±17.74ï¼ng/Lï¼½ and BUN ï¼5.77±2.66ï¼ and ï¼4.74±2.81ï¼U/Lï¼½ between"recurrent"and"non-recurrent"groups ï¼all P>0.05ï¼. ï¼4ï¼ In"recurrent"groupï¼ ground glassï¼ exudative or solid lesions could be found in most of the chest CT performed on re-admission. Meanwhileï¼ fibrosis lesion was relatively rare. ï¼5ï¼ There were no secondary transmissions were found to be caused by the 2019-nCoV"recurrent"group patients. Conclusions: Most of the 2019-nCoV patients had underlying diseases and active lesions were still found in CT imagesï¼ so the possibility of virus replication may still exist. All"recurrent"patients had mild illness which may suggest that they were in recovery stage, and no evidence of transmission is found.
Assuntos
COVID-19/diagnóstico , RNA Viral/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , SARS-CoV-2 , Adulto JovemRESUMO
The effects of salinity on the photodegradation and mineralization of sulfonamides in the UV/TiO2 system were investigated. The goals of this study were to analyze the effects of pH and salinity on the sulfonamide concentration and total organic carbon (TOC) during the removal of sulfonamides in a UV/TiO2 system. Four sulfonamides - sulfadiazine (SDZ), sulfamethizole (SFZ), sulfamethoxazole (SMX) and sulfathiazole (STZ) - were selected as parent compounds. The photodegradation and mineralization rates of sulfonamides in the UV/TiO2 system satisfy pseudo-first-order kinetics. Direct photolysis degraded sulfonamides but sulfonamides cannot be mineralized. The photodegradation and mineralization rate constants in all experiments followed the order pH 5 > pH 7 > pH 9. At pH 5, the mineralization rate constants of SMX, SFZ, SDZ and STZ were 0.015, 0.009, 0.012 and 0.011 min-1, respectively. The addition of NaCl inhibited the mineralization of the four tested sulfonamides more than it inhibited their photodegradation. The inhibitory effect of chloride ions on the removal of sulfonamides in the UV/TiO2 system was attributed to the scavenging by chloride ions of hydroxyl radicals (HOâ¢) and holes and the much lower reactivity of chlorine radicals thus formed, even though the chlorine radicals were more abundant than HOâ¢.
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Sulfonamidas/química , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias , Poluentes Químicos da Água/química , Concentração de Íons de Hidrogênio , Cinética , Fotólise , Salinidade , Sulfonamidas/análise , Titânio , Raios Ultravioleta , Poluentes Químicos da Água/análiseRESUMO
Objective: To establish the patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP. Methods: PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B/c-nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B/c-nu mice through midline laparotomy, 100 µl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high-throughput whole-genome exon sequencing were detected and recorded. Results: The successful rate of established orthotopic PDX model of human PMP was 100% (10/10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity. The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells (PMCA-S), obvious tumor cell atypia and parenchymal invasion.Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX-2 and Ki-67 were positive, MUC6, CK7 and p53 were negative. Whole-exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c. 1621A>C of KIT gene, the mutation abundance was 89.7%. Conclusion: PDX model of PMCA-S is successfully established, which displays the characters of high-degree malignancy, high proliferation and strong aggressiveness.
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Adenocarcinoma Mucinoso/cirurgia , Carcinoma de Células em Anel de Sinete/cirurgia , Pseudomixoma Peritoneal/cirurgia , Adenocarcinoma Mucinoso/patologia , Animais , Biomarcadores Tumorais , Carcinoma de Células em Anel de Sinete/patologia , Xenoenxertos , Humanos , Camundongos , Pseudomixoma Peritoneal/patologiaRESUMO
BACKGROUND: Dental caries in the expanding elderly, predominantly-dentate population is an emerging public health concern. Elderly individuals with heavily restored dentitions represent a clinical challenge and significant financial burden for healthcare systems, especially when their physical and cognitive abilities are in decline. Prescription of higher concentration fluoride toothpaste to prevent caries in older populations is expanding in the UK, significantly increasing costs for the National Health Services (NHS) but the effectiveness and cost benefit of this intervention are uncertain. The Reflect trial will evaluate the effectiveness and cost benefit of General Dental Practitioner (GDP) prescribing of 5000 ppm fluoride toothpaste and usual care compared to usual care alone in individuals 50 years and over with high-risk of caries. METHODS/DESIGN: A pragmatic, open-label, randomised controlled trial involving adults aged 50 years and above attending NHS dental practices identified by their dentist as having high risk of dental caries. Participants will be randomised to prescription of 5000 ppm fluoride toothpaste (frequency, amount and duration decided by GDP) and usual care only. 1200 participants will be recruited from approximately 60 dental practices in England, Scotland and Northern Ireland and followed up for 3 years. The primary outcome will be the proportion of participants receiving any dental treatment due to caries. Secondary outcomes will include coronal and root caries increments measured by independent, blinded examiners, patient reported quality of life measures, and economic outcomes; NHS and patient perspective costs, willingness to pay, net benefit (analysed over the trial follow-up period and modelled lifetime horizon). A parallel qualitative study will investigate GDPs' practises of and beliefs about prescribing the toothpaste and patients' beliefs and experiences of the toothpaste and perceived impacts on their oral health-related behaviours. DISCUSSION: The Reflect trial will provide valuable information to patients, policy makers and clinicians on the costs and benefits of an expensive, but evidence-deficient caries prevention intervention delivered to older adults in general dental practice. TRIAL REGISTRATION: ISRCTN: 2017-002402-13 registered 02/06/2017, first participant recruited 03/05/2018. Ethics Reference No: 17/NE/0329/233335. Funding Body: Health Technology Assessment funding stream of National Institute for Health Research. Funder number: HTA project 16/23/01. Trial Sponsor: Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL. The Trial was prospectively registered.
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Cárie Dentária , Fluoretos , Cremes Dentais , Idoso , Análise Custo-Benefício , Inglaterra , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , EscóciaRESUMO
Objective: To analyze the pathological features of pseudomyxoma peritonei (PMP) in correlation with the survival status and independent prognostic factors. Methods: One-hundred and fifty-five PMP specimens were collected at Beijing Shijitan Hospital, Capital Medical University, from 2012 to 2018. Conventional histopathological evaluation was performed to document the primary tumor site, histopathological type, lymph nodes metastasis, tumor emboli in the blood and lymph vessels, nerve invasion and cellular density. The immunohistochemical parameters including Ki-67, p53, MMR-related protein, MUC2 and MUC5AC were analyzed. Clinical follow-up data were reviewed to correlate with pathological prognostic factors using Kaplan-Meier estimator and Cox proportional hazards regression model for univariate and multivariate analysis. Results: Among 155 PMP patients, there were 77 males and 78 females. There were 98 cases (63.2%) of low-grade peritoneal mucinous carcinomatosis, 49 cases (31.6%) of high-grade peritoneal mucinous carcinomatosis, 8 cases (5.2%) of high-grade mucinous carcinoma peritonei with signet ring cells; only 15 cases (9.7%) with lymph node metastasis; 18 cases (11.6%) with tumor emboli in the blood and lymph vessels; 8/126 (6.3%) were positive dMMR; 100 cases (64.5%) had Ki-67 label index <50%, and 56 cases(36.1%) presented with mutant type p53. Univariate analysis revealed 11 survival-related pathological parameters including gender, age, primary tumor site, histopathological type, lymph node metastasis, tumor emboli in the blood and lymph vessels, nerve invasion, cellular density, Ki-67 label index rate, p53 and dMMR. Multivariate analysis identified 4 independent prognostic factors including the histopathological type (HR 59.78, P<0.01), lymph node metastasis (HR 3.74, P=0.028), nerve invasion (HR 7.81, P=0.007) and dMMR (HR 9.82, P<0.01). Conclusions: Histopathological type is the most important prognostic factor of PMP with dMMR as an independent molecular prognostic indicator.
Assuntos
Neoplasias Peritoneais , Pseudomixoma Peritoneal , Feminino , Humanos , Metástase Linfática , Masculino , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND/PURPOSE: Diffuse reflectance spectroscopy (DRS) is a noninvasive optical technology characterized by relatively low system cost and high efficiency. In our previous study, we quantified the relative concentration of collagen for the individual keloid patient. However, no actual value of collagen concentration can prove the reliability of collagen detection by our DRS system. METHODS: Skin-mimicking phantoms were prepared using different collagen and coffee concentrations, and their chromophore concentrations were quantified using the DRS system to analyze the influence of collagen and other chromophores. Moreover, we used the animal study to compare the DRS system with the collagen evaluation of biopsy section by second-harmonic generation (SHG) microscopy at four different skin parts. RESULTS: In the phantom study, the result showed that coffee chromophore did not severely interfere with collagen concentration recovery. In the animal study, a positive correlation (r=.902) between the DRS system and collagen evaluation with SHG microscopy was found. CONCLUSIONS: We have demonstrated that the DRS system can quantify the actual values of collagen concentration and excluded the interference of other chromophores in skin-mimicking phantoms. Furthermore, a high positive correlation was found in the animal study with SHG microscopy. We consider that the DRS is a potential technique and can evaluate skin condition objectively.
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Colágeno/análise , Pele/química , Animais , Biópsia , Humanos , Masculino , Microscopia , Imagens de Fantasmas , Pele/patologia , Análise Espectral/métodos , Suínos , Porco MiniaturaRESUMO
Objective: To evaluate the safety and efficacy of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS+ HIPEC) in patients with peritoneal carcinomatosis from gastric cancer (GCPC). Methods: The clinical data and follow-up results of GCPC patients treated with CRS+ HIPEC were collected for a retrospective analysis. The primary endpoint was survival rate and the secondary endpoint was safety. Results: A total of 110 GCPC patients accepted CRS+ HIPEC, with a median overall survival (OS) of 13.1 months, and with 1-, 2-, 3-, and 5-year survival rates of 56.4%, 24.9%, 11.2%, and 7.8%, respectively. The perioperative mortality was 0.9%, and the morbidity of serious adverse events was 8.2%. Univariate analysis showed that gender, tumor marker before surgery, PC type, length of surgery, postoperative adjuvant chemotherapy, peritoneal cancer index (PCI), completeness of cytoreduction, HIPEC temperature, and ascites had a significant impact on OS. Multivariate Cox-analysis showed that completeness of cytoreduction, ascites, and postoperative adjuvant chemotherapy were independent factors of OS. Conclusion: CRS+ HIPEC improves survival for GCPC patients with normal preoperative tumor markers, low PCI, no ascites and synchronous PC. Stringent patient selection and complete CRS are two key factors for better survival.
Assuntos
Procedimentos Cirúrgicos de Citorredução , Neoplasias Peritoneais , Neoplasias Gástricas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Terapia Combinada , Humanos , Hipertermia Induzida , Estudos Retrospectivos , Neoplasias Gástricas/terapia , Taxa de SobrevidaRESUMO
Objective: To evaluate the performance of MALDI Biotyper system in identification of clinically isolated pathogens so as to provide a new rapid identification method. Methods: Total 21 270 pathogens strains, isolated from the First Affiliated Hospital of Fujian Medical Universityduring Nov. 2015 to Dec. 2016, were identified by VITEK-â ¡, API and MALDI Biotyper system, respectively.The isolated strains were confirmed by DNA sequencing. Results: The identification of common bacteria with MALDI Biotyper and phenotypic system is highly consistent (>95% and >90%). Among 43 strains of anaerobic bacteria, MALDI Biotyper could identify 90.7% bacteria to species level and 97.7% bacteria to genus level with the statistical significance(χ(2)=6.76, P<0.01), while phenotypic system only identified 65.1% bacteria to species and 69.8% bacteria to genus. Also, no statistical significance was shown for Trichosporon and Candida(P>0.05). MALDI Biotyper could identify 76% filamentous fungi and all of Actinomycetes, Nocardia, Mycobacterium and Legionella to genus level. Conclusions: MALDI Biotyper is an easy-performed, sensitive method for the identification of clinically isolated pathogens. Additionally, the pretreatment and reference database has the effect on identification.
Assuntos
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Fungos , Legionella , Mycobacterium , Análise de Sequência de DNARESUMO
A single nucleotide polymorphism of MYC rs9642880 (G>T) at the 8q24.1 locus is thought to be associated with bladder cancer risk based on the results of genome-wide association studies, but the results remain inconclusive. To assess the association between rs9642880[T] allele and bladder cancer risk, we performed this meta-analysis including 18 case-control studies and involving 23,084 cases and 97,164 controls. Electronic searches for publications were conducted to determine the association between this variant and prostate cancer in several databases. The last search update was August 4, 2014. We used odds ratios and 95%CIs to evaluate the strength of the associations. The overall results suggested that the rs9642880[T] allele was associated with bladder cancer susceptibility (T vs G, odds ratio = 1.18, 95%CI = 1.14-1.22). In subgroup analysis by ethnicity and source of controls, the risk remained significant. The present meta-analysis suggests that the MYC rs9642880[T] allele is significantly associated with bladder cancer risk.
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Estudos de Associação Genética , Proteínas Proto-Oncogênicas c-myc/genética , Neoplasias da Bexiga Urinária/genética , Alelos , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Neoplasias da Bexiga Urinária/patologiaRESUMO
Genome-wide studies have reported an association between the HNF1B rs4430796 (A>G) polymorphism and prostate cancer risk, but results have been inconsistent and recent meta-analyses have been inadequate. This study aimed to integrate previous results and explore the validity of this association. Electronic searches for all relevant publications through May 18, 2014, were conducted across several databases. Additional studies were identified manually, and only the most recent or complete were used in this meta-analysis. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Seven eligible case-control studies were identified, incorporating a total of 14,049 patients and 12,674 controls. Overall, we found that the rs4430796 (A>G) polymorphism had a decreased risk of prostate cancer (GG vs AA: OR = 0.661, 95%CI = 0.615-0.710, P = 0.304; AG vs AA: OR = 0.782, 95%CI = 0.739-0.828, P = 0.435; dominant model: OR = 0.743, 95%CI = 0.704-0.784, P = 0.912; recessive model: OR = 0.764, 95%CI = 0.718-0.813, P = 0.01). Furthermore, in the stratified analysis, there were significantly decreased risks among studies with population- and hospital-based controls. In the subgroup analysis by ethnicity, significantly decreased risks were also found among Caucasians, Americans, and Asians. Our results suggested that the HNF1B rs4430796 (A>G) polymorphism decreased the risk of prostate cancer. In the future, additional and larger studies on patients from across of the world might be required to validate our findings.
Assuntos
Fator 1-beta Nuclear de Hepatócito/genética , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
OBJECTIVE: Fatty liver disease is commonly associated with obesity, insulin resistance and diabetes. Severe fatty liver is sometimes accompanied by steatohepatitis and may lead to the development of hepatocellular carcinoma. At present, there is no effective treatment for non-alcoholic fatty liver disease (NAFLD); thus, recent investigations have focused on developing effective therapeutics to treat this condition. This study aimed to evaluate the effects of kefir on the hepatic lipid metabolism of ob/ob mice, which are commonly used to model fatty liver disease. RESULTS: In this study, we used leptin receptor-deficient ob/ob mice as an animal disease model of NAFLD. Six-week-old ob/ob mice were orally administered the dairy product kefir (140 mg kg(-1) of body weight (BW) per day) for 4 weeks. The data demonstrated that kefir improved fatty liver syndrome on BW, energy expenditure and basal metabolic rate by inhibiting serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities (P<0.05) and by decreasing the triglyceride (TG) and total cholesterol (TC) contents of the liver (P<0.05). Oral kefir administration also significantly reduced the macrovesicular fat quantity in liver tissue. In addition, kefir markedly decreased the expression of the genes sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) (P<0.05) but not the expression of peroxisome proliferator-activated receptor α (PPARα) or hepatic carnitine palmitoyltransferase-1α (CPT1α) in the livers of ob/ob mice. CONCLUSION: On the basis of these results, we conclude that kefir improves NAFLD on BW, energy expenditure and basal metabolic rate by inhibiting the lipogenesis pathway and that kefir may have the potential for clinical application to the prevention or treatment of NAFLD.
Assuntos
Produtos Fermentados do Leite/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Animais , Metabolismo Basal , Biomarcadores/metabolismo , Western Blotting , Modelos Animais de Doenças , Metabolismo Energético , Regulação da Expressão Gênica , Metabolismo dos Lipídeos , Camundongos , Camundongos Knockout , Camundongos Obesos , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Tamanho do Órgão , Receptores para Leptina/deficiência , Transdução de SinaisRESUMO
BACKGROUND: PEP02, also known as MM-398, is a novel nanoliposomal irinotecan that has improved pharmacokinetics and tumour bio-distribution of the free drug. This phase 2 study evaluated PEP02 monotherapy as second-line treatment for pancreatic cancer. METHODS: Patients who had metastatic pancreatic adenocarcinoma, Karnofsky performance status ≥70, and had progressed following gemcitabine-based therapy were eligible. Intravenous injection of PEP02 120 mg m(-2) was given every 3 weeks. Simon 2-stage design was used. The primary objective was 3-month survival rate (OS(3-month)). RESULTS: A total of 40 patients were enrolled. The most common severe adverse events included neutropenia, abdominal pain, asthenia, and diarrhoea. Three patients (7.5%) achieved an objective response, with an additional 17 (42.5%) demonstrating stable disease for a minimum of two cycles. Ten (31.3%) of 32 patients with an elevated baseline CA19-9 had a >50% biomarker decline. The study met its primary end point with an OS(3-month) of 75%, with median progression-free survival and overall survival of 2.4 and 5.2 months, respectively. CONCLUSION: PEP02 demonstrates moderate antitumour activity with a manageable side effect profile for metastatic, gemcitabine-refractory pancreatic cancer patients. Given the limited treatment options available to this patient population, a phase 3 trial of PEP02 (MM-398), referred to as NAPOLI-1, is currently underway.
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Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Sacarose/análogos & derivados , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Camptotecina/uso terapêutico , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Irinotecano , Lipossomos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Terapia de Salvação , Sacarose/uso terapêutico , Resultado do TratamentoRESUMO
Various seed layers were prepared on a Si substrate using the sol-gel (SG) or hydrothermal (HT) method and then ZnO nanocrystal was grown on the seed layer by an HT process. Au/ZnO nanocrystal Schottky diodes (SDs) were fabricated to study the effects of various seed layers on the electrical properties of Au/ZnO SDs. The observations showed that large numbers of Zn vacancies were present near the interface of Au/ZnO with an HT seed layer. The Zn vacancy plays an acceptor-like role, which raises the barrier height of the Au/ZnO SDs to 0.79 eV with a rectifying ratio of more than 8000. Hence, a non-surface-treated Au/ZnO SD was achieved as compared to those of other reported oxygen-plasma treated surfaces. In contrast, oxygen vacancies appear near the interface of Au/ZnO with an SG seed layer. The O vacancy plays a donor-like role, which reduces the barrier height of Au/ZnO, leading to an Ohmic behavior in the I-V characteristics. Zn out-diffusion is found during Au evaporation by of x-ray photoelectron spectroscopy measurements.