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BACKGROUND: Uterine sarcoma is a rare and heterogeneous gynecological malignancy characterized by aggressive progression and poor prognosis. The current study aimed to investigate the relationship between clinicopathological characteristics and the prognosis of uterine sarcoma in Chinese patients. METHODS: In this single-center retrospective study, we reviewed the medical records of 75 patients with histologically verified uterine sarcoma treated at the First Affiliated Hospital of Xi'an Jiaotong University between 2011 and 2020. Information on clinical characteristics, treatments, pathology and survival was collected. Progression-free survival (PFS) and overall survival (OS) were visualized in Kaplan-Meier curves. Prognostic factors were identified using the log-rank test for univariate analysis and Cox-proportional hazards regression models for multivariate analysis. RESULTS: The histopathological types included 36 endometrial stromal sarcomas (ESS,48%), 33 leiomyosarcomas (LMS,44%) and 6 adenosarcomas (8%). The mean age at diagnosis was 50.2 ± 10.7 years. Stage I and low-grade accounted for the majority. There were 26 recurrences and 25 deaths at the last follow-up. The mean PFS and OS were 89.41 (95% CI: 76.07-102.75) and 94.03 (95% CI: 81.67-106.38) months, respectively. Univariate analysis showed that > 50 years, post-menopause, advanced stage, ≥ 1/2 myometrial invasion, lymphovascular space invasion and high grade were associated with shorter survival (P < 0.05). Color Doppler flow imaging positive signals were associated with shorter PFS in the LMS group (P = 0.046). The ESS group had longer PFS than that of the LMS group (99.56 vs. 76.05 months, P = 0.043). The multivariate analysis showed that post-menopause and advanced stage were independent risk factors of both PFS and OS in the total cohort and LMS group. In the ESS group, diagnosis age > 50 years and high-grade were independent risk factors of PFS, while high-grade and lymphovascular space invasion were independent risk factors of OS. CONCLUSION: In Chinese patients with uterine sarcoma, post-menopause and advanced stage were associated with a significantly poorer prognosis. The prognosis of ESS was better than that of LMS. Color Doppler flow imaging positive signals of the tumor helped to identify LMS, which needs to be further tested in a larger sample in the future.
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Neoplasias Uterinas , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Uterinas/patologia , Neoplasias Uterinas/mortalidade , China/epidemiologia , Adulto , Prognóstico , Sarcoma do Estroma Endometrial/patologia , Sarcoma do Estroma Endometrial/mortalidade , Sarcoma/patologia , Sarcoma/mortalidade , Leiomiossarcoma/patologia , Leiomiossarcoma/mortalidade , Idoso , Adenossarcoma/patologia , Adenossarcoma/mortalidade , Adenossarcoma/terapia , Intervalo Livre de ProgressãoRESUMO
Understanding the intricate relationship between prognosis, immune function, and molecular markers in bladder cancer (BC) demands sophisticated analytical methods. To identify novel biomarkers for predicting prognosis and immune function in BC patients, we combined weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression analysis. This was conducted using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Ultimately, we screened the junctional adhesion molecule 3 (JAM3) as an independent risk factor in BC. High levels of JAM3 were linked to adverse clinical parameters, such as higher T and N stages. Additionally, a JAM3-based nomogram model accurately predicted 1-, 3- and 5-year survival rates of BC patients, indicating potential clinical utility. Functional enrichment analysis revealed that high JAM3 expression activated the calcium signaling pathway, the extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway, and was positively correlated with genes associated with epithelial-mesenchymal transition (EMT). Subsequently, we found that overexpression of JAM3 promoted the migration and invasion abilities in BC cells, regulating the expression levels of N-cadherin, matrix metallopeptidase 2 (MMP2), and Claudin-1 thereby promoting EMT levels. Additionally, we showed that JAM3 was negatively correlated with anti-tumor immune cells such as CD8+ T cells, while positively correlated with pro-tumor immune cells such as M2 macrophages, suggesting its involvement in immune cell infiltration. The immune checkpoint CD200 also showed a positive correlation with JAM3. Our findings revealed that elevated JAM3 levels are predictive of poor prognosis and immune cell infiltration in BC patients by regulating the EMT process.
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Biomarcadores Tumorais , Moléculas de Adesão Celular , Transição Epitelial-Mesenquimal , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/mortalidade , Transição Epitelial-Mesenquimal/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Prognóstico , Masculino , Regulação Neoplásica da Expressão Gênica , Feminino , Linhagem Celular Tumoral , Pessoa de Meia-Idade , Movimento Celular/genéticaRESUMO
BACKGROUND: The biological roles of immune-related genes (IRGs) in bladder cancer (BC) need to be further elucidated. OBJECTIVE: To elucidate the predictive value of IRGs for prognosis and immune escape in BC. METHODS: We comprehensively analyzed the transcriptomic and clinical information of 430 cases, including 19 normal and 411 BC patients from the TCGA database, and verified 165 BC cases in the GSE13507 dataset. The risk model was constructed based on IRGs by applying LASSO Cox regression and exploring the relationship between the risk score and prognosis, gene mutations, and immune escape in BC patients. RESULTS: We identified 4 survival-related genes (PSMC1, RAC3, ROBO2 and ITGB3) among 6,196 IRGs in both the TCGA and GES13507 datasets,, which were used to establish a gene risk model by applying LASSO Cox regression. The results showed that the high-risk (HR) group was closely associated with poor survival or advanced pathological stage of BC. Furthermore, the risk score was found to be an independent risk factor for prognosis of BC patients. In addition, high-risk individuals showed a greater prevalence of TP53 mutations lower CD8+ T-cell and NK cell infiltration, higher Treg cell infiltration, higher expression of PD-L1, and higher immune exclusion scores than those in the low-risk (LR) group. Finally, the experimental verification shows that the model construction gene, especially PMSC1, plays an important role in the growth and metastasis of bladder cancer. CONCLUSIONS: These evidences revealed the vital role of IRGs in predicting prognosis, TP53 mutation and immune escape in BC patients.
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Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Neoplasias da Bexiga Urinária/genética , Linfócitos T CD8-Positivos , Bases de Dados Factuais , Perfilação da Expressão GênicaRESUMO
BACKGROUND & AIMS: Sarcopenic obesity (SO), which refers to the coexistence of sarcopenia and obesity. The aim of this systematic review and meta-analysis was first to assess the prevalence of SO in patients with diabetes, and second, to evaluate possible adverse outcomes. METHODS: This study was conducted in adherence to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and the data were collated by means of meta-analysis and narrative synthesis. We comprehensively and systematically searched PubMed, Embase, Web of Science, CBM, CNKI, Wanfang Database from the establishment of the database to December 2022, and collected related studies on SO in patients with diabetes. Using Stata 16.0 software to pool the estimates for the prevalence of SO in patients with diabetes, and a descriptive systematic review of possible adverse outcomes was performed. RESULTS: The prevalence of 20 included studies were pooled by a random-effects model, which showed that the prevalence of SO in patients with diabetes was 27%. Subgroup analyses showed that the prevalence of SO was higher among studies using BIA (24%) to assess muscle mass, and those focused on literature of moderate-quality (29%), being published from 2013 to 2016 (29%), female patients with diabetes (17%), North Americans (30%). SO in patients with diabetes can lead to adverse outcomes including decreased glomerular filtration rate, massive proteinuria, cognitive decline, and insulin resistance. CONCLUSION: The systematic review and meta-analysis revealed a prevalence of 27% for SO in patients with diabetes, and it is associated with potential serious adverse outcomes. Therefore, we should attach importance to the screening of SO in patients with diabetes and early detection of susceptible groups, then selecting appropriate interventions to reduce the occurrence of it and various adverse outcomes in this demographic.
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Diabetes Mellitus , Resistência à Insulina , Sarcopenia , Humanos , Feminino , Sarcopenia/complicações , Sarcopenia/epidemiologia , Prevalência , Obesidade/complicações , Obesidade/epidemiologia , Diabetes Mellitus/epidemiologiaRESUMO
Integrin αvß3/α6ß1 are crucial in the transduction of intercellular cancer information, while their roles in prostate cancer (PCa) remain poorly understood. Here, we systematically analyzed the transcriptome, single nucleotide polymorphisms (SNPs) and clinical data of 495 PCa patients from the TCGA database and verified them in 220 GEO patients, and qPCR was used to validate the expression of the model genes in our patients. First, we found that integrin αvß3/α6ß1 was negatively correlated with most immune cell infiltration and immune functions and closely associated with poor survival in TCGA patients. Then, we divided these patients into two groups according to the expression level of αvß3/α6ß1, intersected differentially expressed genes of the two groups with the GEO dataset and identified eight biochemical recurrence-related genes (BRGs), and these genes were verified by qPCR in our patients. Next, these BRGs were used to construct a prognostic risk model by applying LASSO Cox regression. We found that the high-risk (HR) group showed poorer OS, PFS, biochemical recurrence and clinical characteristics than the low-risk (LR) group. In addition, the HR group was mainly enriched in the cell cycle pathway and had a higher TP53 mutation rate than the LR group. More importantly, lower immune cell infiltration and immune function, higher expression of PD-L1, PD-1, and CTLA4, and higher immune exclusion scores were identified in the HR group, suggesting a higher possibility of immune escape. These findings suggested the key role of integrin αvß3/α6ß1 in predicting prognosis, TP53 mutation and immune escape in PCa.
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Integrina alfaVbeta3 , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/genética , Prognóstico , Ciclo Celular , Bases de Dados FactuaisRESUMO
Heat shock protein member 8 (HSPA8) is one of the most abundant chaperones in eukaryotic cells, but its biological roles in bladder cancer (BC) are largely unclear. First, we observed that HSPA8 was abundant in both cell lines and tissues of BC, and the HSPA8-high group had poorer T stages and overall survival (OS) than the HSPA8-low group in the TCGA patients. Next, when we knocked down HSPA8 in BC cells, the growth and migration abilities were significantly decreased, the apoptosis rates were significantly increased, and the Ki67 fluorescence intensity was decreased in BC cells. Moreover, caspase 3 was significantly decreased with overexpression of HSPA8 in BC cells. After that, a machine learning prognostic model was created based on the expression of HSPA8 by applying LASSO Cox regression in TCGA and GEO patients. The model indicated that the low-risk (LR) group with BC had better tumour stages, lymphovascular invasion, and OS than the high-risk (HR) group. Additionally, the risk score was demonstrated to be an independent risk factor for the prognosis of BC by univariate and multivariate Cox analyses. Moreover, the HR group showed a greater rate of TP53 mutations and was mostly enriched in the ECM-receptor interaction pathway than the LR group. Importantly, lower CD8+ T-cell and NK cell infiltration, higher immune exclusion scores, higher expression of PD-L1 and CTLA4 and poorer immune checkpoint therapy effects were found in the HR group. These findings demonstrated how crucial HSPA8 plays a role in determining the prognosis of bladder cancer.
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Proteínas de Choque Térmico HSC70 , Proteínas de Choque Térmico , Neoplasias da Bexiga Urinária , Humanos , Células Epiteliais , Proteínas de Choque Térmico/genética , Prognóstico , Fatores de Risco , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Proteínas de Choque Térmico HSC70/genética , Proteínas de Choque Térmico HSC70/metabolismoRESUMO
OBJECTIVE: To validate a response surface model for the inhibition of somatic motor response at corrected body weight (CBW) doses of remifentanil plus propofol in elderly patients and to analyze the dose-effect relationship and optimal dosing range for total intravenous anesthesia (TIVA) induction in painless gastroscopy. METHODS: We designed a prospective, open-ended, randomized, parallel group study. A total of 300 elderly patients undergoing painless gastroscopy were randomized to receive remifentanil (0-0.5 µg/kg) and propofol (0.8-2.2 mg/kg) dosing based on CBW. Gastroscopy was performed at the drug's peak effect time. The somatic motor response to gastroscopic stimulation and the adverse reactions at different points were recorded. The somatic motor response was used as the basic element in the subsequent RSM analysis. Model parameters and 95% confidence intervals were fitted by MATLAB software. RESULTS: The CBW doses of remifentanil and propofol showed synergistic inhibitory effects on motor response to noxious stimulation and attenuated adverse reactions. The 50% effective doses of remifentanil and propofol for inhibiting the motor response were 1.754 µg/kg and 2.048 mg/kg, respectively. CONCLUSION: Remifentanil or propofol alone could not inhibit the somatic motor response at weight-adjusted doses among elderly patients. A combination of remifentanil and propofol showed a synergistic interaction in suppressing the motor response and adverse reactions in elderly patients. Preinjection of remifentanil could reduce the needed dose of propofol.
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Background: Low klotho is associated with aging-related traits. However, no study has assessed the association between klotho and oral health in a large sample of population. This study aimed to explore the association between serum α-klotho and oral health in US Adults. Methods: Data were from the National Health and Nutrition Examination Survey. Oral health parameters included periodontitis, self-rated oral health, and tooth loss. Logistic regression and restricted cubic spline models were adopted to evaluate the associations. Results: A total of 6187 participants were included in the study. The median of the α-klotho level was 815.2 pg/mL. Serum α-Klotho was significantly lower in participants with poor oral health (all P <0.01). Compared with the highest tertile, the lowest tertile of α-klotho was associated with moderate/severe periodontitis, poor-rated oral health, and tooth loss, with OR (95% CI) being 1.21 (1.01, 1.48), 1.26 (1.01, 1.56) and 1.38 (1.05, 1.84), respectively. An increment of per 1 standard deviation in the α-klotho concentration was associated with lower odds of moderate/severe periodontitis (OR: 0.93; 95% CI: 0.87, 0.99). Linear dose-response relationships were found between α-klotho and the odds of moderate/severe periodontitis (P for non-linearity=0.88) and poor-rated oral health (P for non-linearity=0.66). An L-shaped dose-response relationship was found between levels of α-klotho and the odds of tooth loss (P for non-linearity=0.04). Conclusions: Serum α-klotho was associated with oral health. Further studies are necessary to clarify the potential mechanisms and demonstrate the predictive ability of klotho in oral diseases.
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Periodontite , Perda de Dente , Adulto , Humanos , Modelos Logísticos , Inquéritos Nutricionais , Saúde Bucal , Periodontite/epidemiologia , Perda de Dente/epidemiologiaRESUMO
Introduction: This meta-analysis evaluated the efficacy and safety of placebo during the maintenance therapy of ovarian cancer (OC) patients in randomized controlled trials (RCTs). Methods: A comprehensive literature review was performed for RCTs published up to and including August 2020 from four electronic databases. We analyzed the efficacy and safety in the control arms of the maintenance therapy in advanced OC patients. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) were estimated in the placebo arms and the observation arms, respectively, using the Frequency Framework method. We also calculated the incidences of common adverse effects (AEs) in the placebo arms. Results: In total, 41 articles with 20,099 (4,787 in the placebo arms, 3,420 in the observation arms, and 11,892 in the experiment arms) patients were included in this meta-analysis. Compared with observation, placebo did not improve or reduce PFS (HR, 1.02; 95% CI, 0.87-1.20; P = 0.81) and OS (HR, 1.02; 95% CI, 0.89-1.16; P = 0.76) of OC patients, while other treatments, except for radiotherapy, significantly improved PFS and OS (all P < 0.05). The incidences of AEs produced by placebo were 94.03% in all grades and 20.22% in grade ≥3. The incidences of AEs were 29.75% in fatigue, 26.38% in nausea, 24.34% in abdominal pain, 18.92% in constipation, 16.65% in diarrhea, 14.55% in vomiting, 13.89% in hypertension, and 13.14% in headache. Conclusions: Placebo did not improve or reduce the PFS and OS benefits of OC patients in RCTs but increased the incidences of AEs.
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BACKGROUND: Uterine sarcoma (US) is a rare malignant uterine tumor with aggressive behavior and rapid progression. The purpose of this study was to constructa comprehensive nomogram to predict cancer-specific survival (CSS) of patients with US-based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: A retrospective population-based study was conducted using data from patients with US between 2010 and 2015 from the SEER database. They were randomly divided into a training cohort and a validation cohort ata 7-to-3 ratio. Multivariate Cox analysis was performed to identify independent prognostic factors. Subsequently, a nomogram was established to predict patient CSS. The discrimination and calibration of the nomogram were evaluated by the concordance index (C-index) and the area under the curve (AUC). Finally, net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA) were used to evaluate the benefits of the new prediction model. RESULTS: A total of 3861 patients with US were included in our study. As revealed in multivariate Cox analysis, age at diagnosis, race, marital status, insurance record, tumor size, pathology grade, histological type, SEER stage, AJCC stage, surgery status, radiotherapy status, and chemotherapy status were found to be independent prognostic factors. In our nomogram, pathology grade had strongest correlation with CSS, followed by age at diagnosis and surgery status. Compared to the AJCC staging system, the new nomogram showed better predictive discrimination with a higher C-index in the training and validation cohorts (0.796 and 0.767 vs. 0.706 and 0.713, respectively). Furthermore, the AUC value, calibration plotting, NRI, IDI, and DCA also demonstrated better performance than the traditional system. CONCLUSION: Our study validated the first comprehensive nomogram for US, which could provide more accurate and individualized survival predictions for US patients in clinical practice.
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Neoplasias Pélvicas , Sarcoma , Neoplasias Uterinas , Feminino , Humanos , Nomogramas , Prognóstico , Estudos Retrospectivos , Programa de SEER , Sarcoma/terapia , Taxa de SobrevidaRESUMO
Governments worldwide have rapidly deployed non-pharmaceutical interventions (NPIs) to mitigate the COVID-19 pandemic. However, the effect of these individual NPI measures across space and time has yet to be sufficiently assessed, especially with the increase of policy fatigue and the urge for NPI relaxation in the vaccination era. Using the decay ratio in the suppression of COVID-19 infections and multi-source big data, we investigated the changing performance of different NPIs across waves from global and regional levels (in 133 countries) to national and subnational (in the United States of America [USA]) scales before the implementation of mass vaccination. The synergistic effectiveness of all NPIs for reducing COVID-19 infections declined along waves, from 95.4% in the first wave to 56.0% in the third wave recently at the global level and similarly from 83.3% to 58.7% at the USA national level, while it had fluctuating performance across waves on regional and subnational scales. Regardless of geographical scale, gathering restrictions and facial coverings played significant roles in epidemic mitigation before the vaccine rollout. Our findings have important implications for continued tailoring and implementation of NPI strategies, together with vaccination, to mitigate future COVID-19 waves, caused by new variants, and other emerging respiratory infectious diseases.
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Our screening data revealed the threat macrolide antibiotics, especially azithromycin (AZN), posed to human health with its increasing occurrence in water environment. The electrochemical sensor based on molecularly imprinted polymer (MIP) is a promising platform that caters for the next generation of intelligent wastewater treatment plants (WWTPs) by virtue of its wide tolerance to water from all sources and in-situ monitoring. However, low initiation potentials of cross-linking monomers contributed by the electron-rich circumstance allowed them to usurp sites designed for functional monomers when electrically stimulated, leading to an unsatisfactory binding capacity. Another uncertainty is that multiple reaction sites of cross-linking monomers granted them complex polymerization routes and made it difficult to ensure the consistency of preparation. Serval monomers had been investigated with electrochemical tools and the performance of sensors constructed with these monomers were compared in this study. Based on the results, we proposed a protocol in which a novel functional monomer possessing a stronger electron-donating group, phenyl, was adopted to compete for the dominance in electropolymerization. Beyond that, the cross-linking monomer was modified with electron-withdrawing groups to raise its initiation potential. A monothiophene with a moderate initiation potential was also recruited as the linker to address the steric hindrance. In this way, polymerization proceeded in a specific order. It is worth mentioning that the Marangoni flow is an ideal tool to deal with the Coffee-ring deposition while drop-casting. The resulting sensor showed good performance with a limitation of detection (LOD) of 0.120 µM for AZN and a satisfactory selectivity, and the design can be applied to constructing sensors for a variety of macrolide antibiotics.
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Impressão Molecular , Antibacterianos , Técnicas Eletroquímicas , Eletrodos , Humanos , Limite de Detecção , Macrolídeos , Polímeros Molecularmente Impressos , Polímeros , Tiofenos , ÁguaRESUMO
BACKGROUND: Previous data show that lidocaine or magnesium has unique characteristics of stress inhibition and antiinflammation. OBJECTIVE: We aimed to observe the effects of lidocaine or magnesium on the quality of recovery (QoR) after laparoscopic cholecystectomy. DESIGN: Single-centre, prospective, randomised, double-blind study. SETTING: The Affiliated Hospital of Xuzhou Medical University from March 2019 to October 2019. PATIENTS: One hundred and fourteen patients scheduled for laparoscopic cholecystectomy. INTERVENTION: The enrolled patients were randomly divided into three groups. Lidocaine (group L), magnesium sulphate (group M) or 0.9% saline (group C) was administered intravenously 10âmin before induction. MAIN OUTCOME MEASURES: The quality of recovery 15 (QoR-15) score, the Hospital Anxiety and Depression Scale (HADS), and the Numerical Rating Scale (NRS) score were selected. The usage of propofol and remifentanil, haemodynamic parameters, anaesthesia recovery parameters and adverse events were also evaluated. RESULTS: The QoR-15 scores for group L (132.0) and group M (134.0) were 6 and 8 points higher than that of group C (126.0) on POD1 (postoperative day 1) (adjPâ<â0.05). However, the decrease of QoR-15 in Group L is less than the minimal clinically important difference (8).The NRS scores on POD1 in group C 3, were higher than other two groups (adjPâ<â0.05). The dosage of remifentanil in group L was lower than other two groups (adjPâ<â0.05).The physical independence of group L and group M and physical comfort of group M were improved compared with group C. CONCLUSION: The results show that magnesium sulphate improved the QoR through improving physical comfort and physical independence in patients after laparoscopic cholecystectomy. However, lidocaine had limited effects on QoR under current conditions. TRIAL REGISTRATION: ChiCTR1800019092 (www.chictr.org.cn). CLINICAL TRIAL NUMBER AND REGISTRY URL: The study was registered in the Chinese Clinical Trials Register (ChiCTR1800019092) https://www.chictr.org.cn.
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Colecistectomia Laparoscópica , Propofol , Colecistectomia Laparoscópica/efeitos adversos , Método Duplo-Cego , Humanos , Lidocaína , Magnésio , Dor Pós-Operatória , Estudos ProspectivosRESUMO
To explore the effect of intrathecal injection of lycopene on pain facilitation, glial activation, and the SIRT1/mTOR pathway in the dorsal horn of rats with burn injury pain (BIP). Here we found that the mechanical pain threshold increased in the lycopene group compared with that of the control group, (P < 0.05). Compared with expression in the sham group, mTOR, pS6, p4EBP, GFAP, and Iba-1 decreased and SIRT1 increased in the lycopene group (P < 0.01). Glial activation in the spinal dorsal horn of BIP rats was alleviated by lycopene (P < 0.01). The SIRT1 and mTOR were mainly distributed in neurons in the spinal dorsal horn in the BIP model. Intrathecal injection of 3-MA (a mTOR agonist) or EX-527 (an inhibitor of Sirt1) partially antagonized lycopene-induced analgesia. Intrathecal injection of rapamycin (an mTOR inhibitor) or SRT1720 (an agonist of Sirt1) induced analgesia in BIP rats. 3-MA abrogated the SRT1720-induced analgesic effects. The present data indicated that the SIRT1/mTOR pathway changed in the spinal dorsal horn of BIP rats; Lycopene alleviated the pain sensitization of BIP rats by regulating the SIRT1/mTOR pathway and glial activation in the spinal dorsal horn.
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Queimaduras/tratamento farmacológico , Queimaduras/metabolismo , Licopeno/administração & dosagem , Sirtuína 1/metabolismo , Corno Dorsal da Medula Espinal/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Carbazóis/administração & dosagem , Injeções Espinhais/métodos , Masculino , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sirtuína 1/antagonistas & inibidores , Corno Dorsal da Medula Espinal/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Resultado do TratamentoRESUMO
At present, most of the drugs have little effect on the pathological process of rheumatoid arthritis (RA). Analgesia is an important measure in the treatment of RA and is also one of the criteria to determine the therapeutic effects of the disease. Some studies have found that crocin, a kind of Chinese medicine, can effectively alleviate pain sensitization in pain model rats, but the mechanism is not clear. Emerging evidence indicates that crocin may inhibit the metastasis of lung and liver cancer cells from the breast by inhibiting Wnt/ß-catenin and the Wnt signaling pathway is closely related to RA. Wnt5a belongs to the Wnt protein family and was previously thought to be involved only in nonclassical Wnt signaling pathways. Recent studies have shown that Wnt5a has both stimulatory and inhibitory effects on the classical Wnt signaling pathway, and so, Wnt5a has attracted increasing attention. This study demonstrated that crocin significantly increased the mechanical thresholds of adjuvant-induced arthritis (AIA) rats, suggesting that crocin can alleviate neuropathic pain. Crocin significantly decreased the levels of pain-related factors and glial activation. Foxy5, activator of Wnt5a, inhibited the above effects of crocin in AIA rats. In addition, intrathecal injection of a Wnt5a inhibitor significantly decreased hyperalgesia in AIA rats. This research shows that crocin may alleviate neuropathic pain in AIA rats by inhibiting the expression of pain-related molecules through the Wnt5a/ß-catenin pathway, elucidating the mechanism by which crocin relieves neuropathic pain and provides a new way of thinking for the treatment of AIA pain.
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Artrite Reumatoide/metabolismo , Carotenoides/administração & dosagem , Hiperalgesia/metabolismo , Neuralgia/metabolismo , Neuroglia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Hiperalgesia/prevenção & controle , Masculino , Neuralgia/prevenção & controle , Neuroglia/metabolismo , Ratos Sprague-Dawley , Proteína Wnt-5a/metabolismo , beta Catenina/metabolismoRESUMO
OBJECTIVE: To perform a comprehensive meta-analysis to systematically assess the value of abnormal muscle response (AMR) in predicting the surgical outcome of patients with hemifacial spasm. METHODS: The electronic database PubMed, Embase, Web of Science, and ScienceDirect were searched, and relevant articles were identified up to September 30, 2019. These data were extracted for pooled analysis, heterogeneity testing, sensitivity analysis, publication bias analysis, and Fagan plot analysis. RESULTS: The disappearance of AMR during microvascular decompression was associated with a favorable short-term surgical outcome (pooled relative risk [RR], 1.42; 95% confidence interval [CI], 1.24-1.62; pooled RR adjusted for publication bias, 1.30; 95% CI, 1.08-1.57). The corresponding pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.91 (95% CI, 0.88-0.94), 0.34 (95% CI, 0.27-0.42), 1.4 (95% CI, 1.2-1.6), 0.26 (95% CI, 0.17-0.38), and 5 (95% CI, 3-9), respectively. The disappearance of AMR was almost ineffective in predicting the long-term surgical outcome (pooled RR, 1.09; 95% CI, 1.02-1.17; pooled RR adjusted for publication bias, 1.001; 95% CI, 0.92-1.09). The corresponding pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.90 (95% CI, 0.85-0.93), 0.28 (95% CI, 0.20-0.37), 1.2 (95% CI, 1.1-1.4), 0.38 (95% CI, 0.22-0.63), and 3 (95% CI, 2-6), respectively. CONCLUSIONS: The disappearance of AMR during microvascular decompression demonstrates limited prognostic value for a favorable short-term outcome, and does not appear effective in predicting the long-term outcome of patients with hemifacial spasm.
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Músculos Faciais/fisiologia , Espasmo Hemifacial/cirurgia , Cirurgia de Descompressão Microvascular/métodos , Espasmo Hemifacial/fisiopatologia , Humanos , Monitorização Intraoperatória , Prognóstico , Resultado do TratamentoRESUMO
BACKGROUND: To systematically review the clinical value of 18F-DCFPyL prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) in the diagnosis of prostate cancer (PCa). METHODS: Literature concerning 18F-DCFPyL PSMA PET/CT in the diagnosis of prostate cancer published from 2015 to 2020 was electronically searched in the databases including PubMed and Embase. Statistical analysis was carried out with STATA 15 software, and the quality of included studies was tested with quality assessment of diagnostic accuracy studies (QUADAS) items. The heterogeneity of the included data was tested. RESULTS: In total, nine pieces of literature involving 426 patients met the inclusion criteria. The heterogeneity of the study group was not obvious. The SEN, SPE, LR+, LR-, DOR as well as AUC of 18F-DCFPyL PSMA PET/CT diagnosis of prostate cancer were 0.91, 0.90, 8.9, 0.10, 93, and 0.93. The pooled DR of 18F-DCFPyL labeled PSMA PET/CT in PCa was 92%. The pooled DR was 89% for PSA≥0.5 ng/ml and 49% for PSA < 0.5ng/ml. CONCLUSION: 18F-DCFPyL PSMA PET/CT had good sensitivity and specificity for the diagnosis of prostate cancer. The DR of 18F-DCFPyL PSMA PET/CT was correlated with PSA value. Further large-sample, high-quality studies were needed.
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Excessive autophagy is one of the crucial factors of cerebral ischemia-reperfusion injury (CIRI), which has been demonstrated to be one of the targets for acupuncture treatment of ischemic stroke. In the present paper, we make a review about the development of acupuncture intervention induced improvement of CIRI (such as reducing the infarction area, improving learning-memory ability and motor function) by regulating autophagy in animal studies. Outcomes showed that acupuncture intervention can function in 1) inhibiting CIRI-induced increase of the number of lysosomes and autophagic lysosomes, and relieving structural injury of mitochondria, and reducing the number of autophagosome in the central region of the ischemic cerebral cortex tissue; 2) down-regulating the expression of microtubule-associated protein â ¡ light chain 3 (LC3â ¡) and the ratio of LC3-â ¡/LC3-â in the ischemic cerebral region, and 3) regulating the expression of Beclin 1 (autophagy-related gene), promoting the expression of P62 (autophagy-related adaptor protein). In addition, acupuncture can also regulate phosphoinositide 3 kinase (PI3K)- protein kinase B (AKT)- mammalian target of rapamycin complex 1(mTOR) signaling at different time-points (down-regulation at the early stage and up-regulation at the later stage), and activating AMP-activated protein kinase (AMPK)-mTOR- UNC51-like kinase-1 signaling to relieve cerebral ischemic injury. These results reveal some mechanisms of acupuncture therapy underlying improvement of CIRI and provide experimental basis for clinical application of acupuncture therapy in the treatment of ischemic stroke.
Assuntos
Terapia por Acupuntura , Autofagia , Traumatismo por Reperfusão , Animais , Proteína Beclina-1 , Fosfatidilinositol 3-QuinasesRESUMO
BACKGROUND: Scrub typhus is a life-threatening disease caused by Orientia tsutsugamushi, and specific antimicrobial medicine is available. Early and accurate diagnosis is essential for reducing the risk of severe complications and death. In this study, we aimed to evaluate the case diagnosis situation among medical care institutions and geographical regions in China, and the results will benefit both clinical practice and the disease surveillance system. METHODS: We extracted individual scrub typhus case data 2006-2016 from a national disease surveillance system in China. The diagnosis category and interval time from illness onset to diagnosis were compared among three levels of medical care institutions and provinces. The descriptive analysis method was performed in our study. RESULTS: During the 11-year study period, 93 481 scrub typhus cases, including 57 deaths, were recorded in the nationwide surveillance system. The overall proportion of laboratory-confirmed cases was only 4.7%, and this proportion varied greatly among primary medical centres (2.8%), county level hospitals (4.2%), and city level hospitals (6.3%). Notably, the proportion of laboratory-confirmed cases has consistently decreased from 16.3% in 2006 to 2.6% in 2016, and the same decreasing trend was found among all three levels of medical care institutions. The interval from illness onset to case diagnosis (Tdiag) for all cases was 5 days (interquartile range [IQR]: 2-9 days) and decreased from 7 days (IQR: 3-11 days) in 2006 to 5 days (IQR: 2-8 days) in 2016. The risk of death for patients with a Tdiag of > 7 days was 2.2 times higher (OR = 2.21, 95% CI: 1.05-5.21) than that of patients with a Tdiag of < 2 days. CONCLUSIONS: The interval time from illness onset to diagnosis for scrub typhus cases decreased greatly in China; however, the diagnosis rate of cases with laboratory-confirmed results must be increased among all levels of medical care institutions to reduce both the risk of death and the misuse of antibiotics associated with scrub typhus.
Assuntos
Orientia tsutsugamushi/fisiologia , Vigilância da População , Tifo por Ácaros/diagnóstico , China/epidemiologia , Humanos , Tifo por Ácaros/epidemiologiaRESUMO
Electroacupuncture is known as an effective adjuvant therapy in ischemic cerebrovascular disease. However, its underlying mechanisms remain unclear. Studies suggest that autophagy, which is essential for cell survival and cell death, is involved in cerebral ischemia reperfusion injury and might be modulate by electroacupuncture therapy in key ways. This paper aims to provide novel insights into a therapeutic target of electroacupuncture against cerebral ischemia/reperfusion injury from the perspective of autophagy. Here we review recent studies on electroacupuncture regulation of autophagy-related markers such as UNC-51-like kinase-1 complex, Beclin1, microtubule-associated protein-1 light chain 3, p62, and autophagosomes for treating cerebral ischemia/reperfusion injury. The results of these studies show that electroacupuncture may affect the initiation of autophagy, vesicle nucleation, expansion and maturation of autophagosomes, as well as fusion and degradation of autophagolysosomes. Moreover, studies indicate that electroacupuncture probably modulates autophagy by activating the mammalian target of the rapamycin signaling pathway. This review thus indicates that autophagy is a therapeutic target of electroacupuncture treatment against ischemic cerebrovascular diseases.