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Zinc finger protein 180 (ZNF180) is a multifunctional protein that interacts with nucleic acids and regulates various cellular processes; however, the function of ZNF180 in colorectal cancer (CRC) remains unclear. The present study investigated the role and function of ZNF180 in CRC, and aimed to reveal the underlying molecular mechanism. The results revealed that ZNF180 was downregulated in CRC tissues and was associated with a good prognosis in patients with CRC. Additionally, the expression of ZNF180 was downregulated by methylation in CRC. In vivo and in vitro experiments revealed that ZNF180 overexpression was functionally associated with the inhibition of cell proliferation and the induction of apoptosis. Mechanistically, chromatin immunoprecipitationPCR and luciferase assays demonstrated that ZNF180 markedly regulated the transcriptional activity of methyltransferase 14, N6adenosinemethyltransferase noncatalytic subunit (METTL14) by directly binding to and activating its promoter region. Simultaneous overexpression of ZNF180 and knockdown of METTL14 indicated that the reduction of METTL14 could suppress the effects of ZNF180 on the induction of apoptosis. Clinically, the present study observed a significant positive correlation between ZNF180 and METTL14 expression levels, and low expression of ZNF180 and METTL14 predicted a poor prognosis in CRC. Overall, these findings revealed a novel mechanism by which the ZNF180/METTL14 axis may modulate apoptosis and cell proliferation in CRC. This evidence suggests that this axis may serve as a prognostic biomarker and therapeutic target in patients with CRC.
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Apoptose , Proliferação de Células , Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Metiltransferases , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Apoptose/genética , Proliferação de Células/genética , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Animais , Ativação Transcricional , Camundongos , Regiões Promotoras Genéticas , Idoso , Regulação para Baixo , Metilação de DNARESUMO
BACKGROUND: This study aimed to evaluate the long-term risk of CKD and renal function declines using a combination of diuretics and SGLT2i. METHODS: We selected the data of subjects who had at least two outpatient records or at least one inpatient record for DM treatment as the DM group from the National Health Insurance Research Database (NHIRD). Patients receiving versus not receiving SGLT2i were defined as the SGLT2i and non-SGLT2i cohorts, respectively. The patients in the two groups were matched 1:1 through propensity score matching based on age, sex, year of index date, and comorbidities. RESULTS: The diuretics-only group had a higher risk of CKD (aHR, 2.46; 95% CI, 1.68-3.61) compared to the neither SGLT2i nor diuretics group, while the both SGLT2i and diuretics group and the SGLT2i only group had lower risks (aHR, 0.45, 95% CI, 0.32-0.63; aHR, 0.26, 95% CI, 0.17-0.40) than the diuretics-only group. The SGLT2i-only group had a lower risk (aHR, 0.58, 95% CI, 0.36-0.94) than the both SGLT2i and diuretics group. CONCLUSION: This study indicates that diuretics could raise the risk of CKD in diabetic patients, but when used in combination with SGLT2i, they continue to offer protection against CKD.
Assuntos
Pacientes Internados , Insuficiência Renal Crônica , Humanos , Taiwan/epidemiologia , Estudos Retrospectivos , Diuréticos/efeitos adversos , Insuficiência Renal Crônica/epidemiologiaRESUMO
Air pollution triggers a tissue-specific inflammatory response. However, studies on the association between exposure to air pollutants and chronic rhinosinusitis (CRS) risk remain limited. Thus, we conducted this nationwide study to define the association between air pollution and CRS. We used the Longitudinal Health Insurance Database (LHID) and Taiwan Air Quality-Monitoring Database (TAQMD) to conduct a population-based cohort study. Study participants were recruited from the LHID, a data subset of the National Health Insurance Research Database that randomly sampled one million individuals. TAQMD has been an air pollutant database since 1998. In univariate and multivariate Cox proportional hazards regression models, adjusted hazard ratios (aHRs) and 95% CIs of CRS in five air pollutants were accounted. We adjusted for age, sex, urbanization level, insurance fee, comorbidities, and pollutant levels in the multivariate model. The total number of participants enrolled in this study was 160,504. The average age was 40.46 ± 14.62 years; males constituted 43.8% of the total participants. The percentages of alcoholism, tobacco dependence, and COPD were 1.5%, 2.8%, and 28.3%, respectively. After adjustment for age, sex, urbanization level, insurance fee, and comorbidities, the highest levels of air pollutants, including PM2.5 (aHR = 1.14, 95% CI = 1.06-1.22), NO2 (aHR = 1.07, 95% CI = 1.00-1.15), and PM10 (aHR = 1.13, 95% CI = 1.05-1.21) had a significantly greater CRS risk; we selected the lower concentration as the reference but did not correlate with CO. We found a significantly increased risk of CRS in residents with air pollutant exposure.
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Air pollutants as risk factors for benign brain tumor (BBT) remain unclear. Therefore, we conducted a nationwide retrospective cohort study by integrating the patients' clinical data and daily air quality data to assess the environmental risk factors of BBT in Taiwan.Daily air quality data were categorized into quartiles (Q1 to Q4). The adjusted hazard ratio (aHR) was evaluated by comparing the BBT incidence rate of the subjects in Q2-Q4 with that of the subjects in Q1 (the lowest concentration of air pollutants). A total of 161,213 subjects were enrolled in the study. Among the air pollutants tested, the aHR of BBT was significantly higher in the subjects who were exposed to the highest level (Q4) of CO (aHR 1.37, 95% CI 1.08-1.74), NO2 (aHR 1.40, 95% CI 1.09-1.78), and PM2.5 (aHR 1.30, 95% CI 1.02-1.65) than that in the subjects who were exposed to the lowest level (Q1). No significant risk association of BBT with SO2 and PM10 exposure was observed. The results revealed that long-term exposure to air pollutants, particularly CO, NO2, and PM2.5, is associated with the risk of BBT.
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ABSTRACT: Lymphatic malformations are rare benign malformations that predominantly occur in the head and neck region. The advent of surgical robots in head and neck surgery may provide beneficial outcomes for pediatric patients. Here, we describe our experiences with transhairline incisions for robot-assisted surgical resection of cervical lymphatic malformations in pediatric patients.In this prospective longitudinal cohort study, we recruited consecutive patients under 18âyears of age who were diagnosed with congenital cervical lymphatic malformations and scheduled for transhairline approach robotic surgery at a single medical center. We documented the docking times, console times, surgical results, complications, and postoperative follow-up outcomes.The studied patients included 2 with mixed-type lymphatic malformations and 2 with macrocystic-type lymphatic malformations. In all 4 patients, the incision was hidden in the hairline; the incision length was <5âcm in 3 patients but was extended to 6âcm in 1 patient. Elevating the skin flap and securely positioning it with Yang retractor took <1âhour in all cases. The mean docking time was 5.5âminutes, and the mean console time was 1âhour and 46âminutes. All 4 surgeries were completed endoscopically with the robot. The average total drainage volume in the postoperative period was 21.75âmL. No patients required tracheotomy or nasogastric feeding tubes. Neither were adverse surgery-associated neurovascular sequelae observed. All 4 patients were successfully treated for their lymphatic malformations, primarily with robotic surgical excisions.Cervical lymphatic malformations in pediatric patients could be accessed, properly visualized, and safely resected with transhairline-approach robotic surgery. Transhairline-approach robotic surgery is an innovative method for meeting clinical needs and addressing esthetic concerns.
Assuntos
Vértebras Cervicais/cirurgia , Doenças Linfáticas/cirurgia , Procedimentos Ortopédicos/normas , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Doenças Linfáticas/fisiopatologia , Masculino , Procedimentos Ortopédicos/métodos , Procedimentos Ortopédicos/estatística & dados numéricos , Pediatria/métodos , Pediatria/tendências , Estudos Prospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/normas , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricosRESUMO
BACKGROUND: Post-pubertal teratomas, which mostly occur at 20 to 40 years old, are more likely to be found at a metastatic site in up to 20% of cases and may be inadvertently overlooked. We present a case of cervical malignant teratoma that masqueraded as a hematoma.Case presentation: A 24-year-old man presented to our institution with a 4-month history of a progressively relapsing painless mass in the neck, despite conservative treatments with oral medications. A huge space-occupying mass was identified with almost total occlusion of the left internal jugular vein. The likely diagnosis was an organized hematoma or congenital cystic tumor with internal hemorrhage. Surgical excisional biopsy of the mass lesion was conducted and a malignant teratoma was found. A whole-body positron emission tomography scan showed a left inguinal mass, bilateral intra-abdominal lymphadenopathies, and abdominal metastases. Histopathology further suggested the diagnosis of an immature testicular teratoma with multiple lymph node metastases. The patient received adjuvant chemotherapy with a bleomycin, etoposide, and cisplatin regimen. During follow-up, salvage second-line chemotherapy was required with a paclitaxel, ifosfamide, and cisplatin regimen. CONCLUSION: Although uncommon, cervical teratoma should be taken into consideration once a painless and non-remitting mass lesion is found in a young adult.
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Teratoma , Neoplasias Testiculares , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino/uso terapêutico , Hematoma/diagnóstico por imagem , Hematoma/cirurgia , Humanos , Masculino , Recidiva Local de Neoplasia , Teratoma/diagnóstico por imagem , Teratoma/cirurgia , Adulto JovemRESUMO
This study aims to investigate the molecular characteristics of Chinese gastric cancer patients. In our study, the KRAS, BRAF, and PIK3CA mutation status of 485 GC patients were analyzed by Sanger sequencing. Kaplan-Meier analysis was used to plot survival curves according to different genotypes. The results show that the frequency of KRAS, BRAF and PIK3CA mutations were 4.1%, 1.2% and 3.5%, respectively. BRAF mutations were significantly concentrated in stage III and IV gastric cancer (P=0.009). KRAS G12V mutation carriers have much shorter OS than other mutation carriers and wild-type group patients (P=0.013). In conclusion, only the KRAS G12V mutation has an adverse effect on patient survival.
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Psoriasis is a common chronic inflammatory disease in which T-helper 1(Th1) and T-helper 17(Th17) cells play an important role in its pathology. Formula PSORI-CM01 was a novel formulated Chinese medicine used for psoriasis therapy. It had been demonstrated previously that PSORI-CM01 and serum contained Formula PSORI-CM01 (PCM01CS) could improve psoriasis by inhibiting the epithelial hyperplasia, how PSORI-CM01 affects inflammatory cytokine and chemokine in dermis is still unknown. In this study we found PSORI-CM01 pre-treated 3days before IMQ painting could ameliorated IMQ-induced mice skin lesion as PASI score was apparently reduced. Th1 related cytokine IFN-γ and Th17 related cytokine IL-17/IL-22 was used to induce inflammatory models on human keratinocyte cell line HaCaT in vitro, respectively. PCM01CS significantly reduced IFN-γ induced mRNA expression of IL-6, IL-12 and CXCL-10, reduced IL-6 and CXCL-10 release into HaCaT supernatant. 20ng/ml IL-17/IL-22 co-stimulation significantly upregulated expression of IL-6, IL-8 and CCL20 mRNA expression in HaCaT cells, PCM01CS significantly inhibit these cytokines expression both in mRNA and in protein levels. Finally, PCM01CS could obviously inhibit nuclear NF-κB p65 expression which activated by IFN-γ and IL-17/IL-22 stimulation. Thus, our new findings reveal that Formula PSORI-CM01 may possess therapeutic action on psoriasis by inhibiting inflammatory within skin environments.
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Anti-Inflamatórios/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Queratinócitos/efeitos dos fármacos , Psoríase/tratamento farmacológico , Pele/efeitos dos fármacos , Células Th1/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Animais , Linhagem Celular , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Queratinócitos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Psoríase/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Pele/patologia , Células Th1/imunologia , Células Th17/imunologiaRESUMO
BACKGROUND: Psoriasis is a chronically recurrent inflammatory skin disease, modern medicine could achieve good therapeutic effect, but these treatments led to recurrence of the psoriasis, more severe symptoms due to damaging skin barrier. Traditional Chinese medicine is a useful alternative therapies. The purpose of this study was to explore the mechanism of PSORI-CM01, a Chinese medicine formula for psoriasis therapy, in eliminating psoriasis by studying its effects on inhibiting epidermal hyperplasia. METHODS: Imiquimod induced psoriasis-form mice model was used to determine the efficacy of PSORICM-01 by assessing the improvement of hyperplasia in epidermal and dermal skin, cyclin B2 expression in skin was detected by immunochemistry. Human keratinocyte cell line HaCaT stimulated by LPS or not was used to research molecular mechanisms of PSORIMCM-01 as in vitro model. The inhibition of proliferation of HaCaT was determined by MTT assay, BrdU assay and real-time cell analysis (RTCA). Cell cycle distribution was detected by flow cytometry. Real-Time PCR and western blot analysis was performed to quantify the mRNA and protein expression levels, respectively. The ability of PSORICM-01 to inhibit proliferation of cyclin B2 overexpressed HaCaT cell were also investigated. RESULTS: PSORI-CM01 significantly inhibited epidermal hyperplasia in IMQ mice lesion skin, and reduced expression of epidermis cyclin B2. Serum containing PSORI-CM01 dramatically inhibited keratinocyte HaCaT cell proliferation, no matter stimulated by LPS or not. FACS analysis showed ability of PSORICM-01 to arrest cell cycle in the G2/M phase. Additionally, PSORI-CM01 significant downregulated mRNA and protein expression of cyclin B2, and over-expression of cyclin B2 antagonized the anti-proliferative effect of PSORI-CM01 on HaCaT cells. CONCLUSIONS: PSORI-CM01 inhibits epidermal hyperplasia in imiquimod-induced mouse psoriasis-form model and reduces keratinocyte proliferation in vitro. Our results indicate that PSORI-CM01 may possess therapeutic potential for psoriasis by inhibiting keratinocyte proliferation through downregulation of cyclin B2.