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Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.
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Antituberculosos , Nitroimidazoles , Oxazoles , Rifampin , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis Pulmonar , Humanos , Masculino , Femenino , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Estudios Prospectivos , Rifampin/efectos adversos , Persona de Mediana Edad , Oxazoles/efectos adversos , Oxazoles/uso terapéutico , Oxazoles/administración & dosificación , Antituberculosos/efectos adversos , Tuberculosis Pulmonar/tratamiento farmacológico , Nitroimidazoles/efectos adversos , Nitroimidazoles/uso terapéutico , Nitroimidazoles/administración & dosificación , Anciano , China , Adulto Joven , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiologíaRESUMEN
Objective: To explore the relationship between insomnia and osteoporosis. Methods: Mendelian randomization (MR) analysis were used in this study. The single nucleotide polymorphisms (SNPs) related to insomnia from genome-wide association analysis research data were selected as the instrumental variables by using inverse variance weighted (IVW), MR-Egger regression, weighted median method, maximum likelihood, penalized weighted median estimator, and Mendelian randomization robust adjusted profile score (MR-RAPS) to determine the causal relationship between insomnia and osteoporosis. Odds ratio (OR) and 95% confidence interval (CI) values were used to evaluate the association between insomnia and osteoporosis. Cochran's Q-test was used to detect heterogeneity of SNPs, MR-Egger regression was used to test for level pleiotropy, and the leave-one-out method was used to test sensitivity, MR pleiotropy residual sum and outlier (MR-PRESSO) method and radial MR were used to detect erroneous outliers. Results: The screening criteria were set based on the three major assumptions of MR; finally, 31 SNPs were included in the MR analysis. The results of MR causal effect analysis using the IVW method showed that insomnia increased the risk of osteoporosis by about 0.7% (OR=1.007, 95%CI 1.001-1.014, P=0.044); heterogeneity testing showed heterogeneity between SNPs (Q=57.91, P<0.001); and the MR- Egger intercept test did not indicate horizontal pleiotropy in this study (intercept value=3.807×10-5, P=0.888). Leave-one-out method showed that no single SNP had a significant impact on the overall results. No abnormal SNP was detected according to the MR-PRESSO results (P=0.059), and radial MR did not detect any outliers. Conclusion: Mendelian randomization analysis showed that insomnia can increase the risk of osteoporosis.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Osteoporosis , Polimorfismo de Nucleótido Simple , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Osteoporosis/genética , Osteoporosis/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/genética , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Factores de RiesgoRESUMEN
Allogeneic chimeric antigen receptor (CAR)-expressing T cells offer many advantages over autologous therapies, but their benefits are curtailed by graft-versus-host disease and elimination by recipient immune cells. Moreover, just as with autologous therapies, allogeneic CAR T cells are susceptible to activation-induced cell death (AICD) caused by chronic antigen exposure (CAE). Granzyme B- and Fas/Fas ligand-initiated caspase-mediated apoptoses are key mechanisms of T-cell death caused by T/NK cell-mediated allorejection or CAE. We explored a protective strategy of engineering CAR T cells to overexpress variants of the Granzyme B-specific serine protease inhibitor SERPINB9 (SB9) to improve allogeneic T-cell persistence and antitumor efficacy. We showed that the overexpression of an SB9 variant with broadened caspase specificity, SB9(CAS), not only significantly reduced rejection of allogeneic CAR T cells but also increased their resistance to AICD and enabled them to thrive better under CAE, thus improving allogeneic T-cell persistence and antitumor activity in vitro and in vivo. In addition, although SB9(CAS) overexpression improved the efficacy of allogeneic CAR T-cell therapy by conferring protection to cell death, we did not observe any autonomous growth, and the engineered CAR T cells were still susceptible to an inducible suicide switch. Hence, SB9(CAS) overexpression is a promising strategy that can strengthen current development of cell therapies, broadening their applications to address unmet medical needs.
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Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Serpinas , Linfocitos T , Animales , Humanos , Serpinas/genética , Serpinas/metabolismo , Inmunoterapia Adoptiva/métodos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Ratones , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Línea Celular TumoralRESUMEN
Objective: To explore the efficacy of arthroscopic release in treating postoperative knee adhesion and investigate the influence of release timing on the treatment outcomes. Methods: A total of 50 patients who accepted arthroscopic release in Peking University Third Hospital from February 2017 to December 2021 were included in the retrospective cohort. The study cohort comprised 28 men and 22 women, with a mean age of (30.8±11.9) years. All the primary surgeries were manipulated under arthroscopes. A comparison was made between pre-and postoperative range of motion (ROM), visual analog scale (VAS), International Knee Documentation Committee (IKDC) scores, and Tegner activity scale scores for the patients. According to the interval between the appearance of adhesion and arthroscopic release, the patients were divided into four groups:<3 months group (n=12), 3-6 months group (n=16),>6-12 months group (n=14), and>12 months group (n=8). Inter-group comparisons on postoperative ROM, IKDC scores, and Tegner activity scale scores and improvement values of each outcome were conducted. Results: All the patients were followed up for (36.4±19.7) months. Patients gained significant improvement in flexion, extension, IKDC scores, and Tegner scores (125.0°±20.0° vs 75.7°±27.5°, 2.3°±4.8° vs 7.4°±7.3°, 69.8±17.7 vs 51.4±12.8, 4.1±2.1 vs 2.2±1.1) (all P<0.05), while the VAS scores did not show significant improvement. There were no significant differences among different groups in postoperative extension, IKDC scores or Tegner scores, nor in their improvements. However, patients in the ≤6 months group could gain better postoperative flexion and improvement in flexion than those in the >6 months group (129.9°±20.0° vs 118.8°±17.4°, 58.6°±32.8° vs 37.3°±23.1°) (P<0.05). Conclusions: Arthroscopic release presents a great effect in treating knee adhesion after arthroscopic operation. Once the symptoms of adhesion appear and physical rehabilitation fails to improve the ROM, one should accept early surgical intervention (less than 6 months) for a better outcome.
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Artroscopía , Articulación de la Rodilla , Rango del Movimiento Articular , Humanos , Femenino , Masculino , Adulto , Estudios Retrospectivos , Articulación de la Rodilla/cirugía , Adherencias Tisulares , Resultado del Tratamiento , Complicaciones Posoperatorias , Factores de TiempoRESUMEN
Background: Cellular senescence has been associated with neurodegenerative disease and clearance of senescent cells using genetic or pharmaceutical strategies (senolytics) has demonstrated beneficial effects in mouse models investigating individual disease etiologies of Alzheimer's disease (AD). However, it has remained unclear if senescent cell clearance in a mouse model exhibiting both plaque and tau pathologies modifies the disease state (3xTg). Objective: To investigate the effects of senescent cell clearance in the 3xTg mouse model. Methods: 3xTg mice were treated with senolytics (ABT263 (navitoclax; NAVI), a combination of dasatinib and quercetin (D+Q)), or subjected to transgene-mediated removal of p16-expressing cells (via INK-ATTAC). Results: Senolytic treatments consistently reduced microgliosis and ameliorated both amyloid and tau pathology in 3xTg mice. Using RNA sequencing, we found evidence that synaptic dysfunction and neuroinflammation were attenuated with treatment. These beneficial effects were not observed with short-term senolytic treatment in mice with more advanced disease. Conclusions: Overall, our results further corroborate the beneficial effects senescent cell clearance could have on AD and highlight the importance of early intervention for the treatment of this debilitating disease.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Ratones , Animales , Enfermedad de Alzheimer/patología , Enfermedades Neurodegenerativas/complicaciones , Senoterapéuticos , Ratones Transgénicos , Senescencia Celular , Modelos Animales de Enfermedad , Proteínas tau/genética , Proteínas tau/farmacologíaRESUMEN
Exploring the clinical value of multiparametric magnetic resonance (Mp-MRI)-cognitive fusion method of targeted transperineal prostate puncture combined with rapid pathological diagnosis. Patients with suspected prostate cancer admitted to our hospital from 2022.01 to 2023.05 were selected as the study subjects, and Mp-MRI was performed and the suspected lesions were scored by the Prostate Imaging Reporting and Data System (PI-RADS). The enrolled patients were randomly divided into the transperineal prostate targeted puncture plus rapid pathology group (experimental group) and the transperineal prostate systematic combined targeted puncture plus conventional pathology group (control group), and the positive puncture rate, pathological findings, and complications were analyzed to compare the differences between the two groups. A total of 100 patients were enrolled, 53 in the experimental group [age 55-89 years, (73.17±7.79) years; tPSA 7.01-100 µg/L, mean 21.34 (12.38, 44.42) µg/L]and 47 in the control group [age 60-87 years, (71.96±7.07) years; tPSA 6.11-98.82 µg/L, mean 18.77 (9.04, 38.09) µg/L], and there was no significant difference between the two groups in the diagnostic positivity rate of overall PCa and clinically significant PCa (P>0.05); there was no significant difference in the highest Gleason score of pathological tissues between the two groups (P>0.05); the number of cases of medically induced sarcoid hematuria in the experimental group were significantly reduced compared with the control group (P<0.05). In terms of biopsy pain score (VAS), patients in the experimental group experienced less pain than those in the control group (P<0.05). The Mp-MRI-cognitive fusion method of transperineal targeted prostate puncture combined with rapid frozen section pathological examination can provide rapid and accurate pathological results, reduce the chance of post-puncture complications, and alleviate the pain caused by puncture sampling, which has high clinical value.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Imagen por Resonancia Magnética , Punciones , DolorRESUMEN
Objective: To analyze the case fatality rate of HIV/AIDS cases and influencing factors in Jingzhou. Methods: The data were retrieved from HIV/AIDS Comprehensive Response Information System and the cases diagnosed with HIV/AIDS in Jingzhou during 1996-2021 and aged 15 years or older were selected for the study. The death curve was drawn with Kaplan-Meier method, and Cox proportional-hazards model was used to identify influencing factors for death. Results: A total of 3 304 HIV/AIDS cases were followed up for 16 091.5 person-years, and 893 cases died, with a case fatality rate of 5.5/100 person-years. The cumulative case fatality rates of 1, 5 and 10 years were 15.4%, 25.0% and 34.6% respectively, the cumulative case fatality rates of 1, 5 and 10 years were 6.9%, 14.4% and 23.7% in the cases with access to antiretroviral therapy (ART), and 68.0%, 90.1% and 98.7% in the cases without access to ART. The results of Cox proportional hazards regression model showed that the risk for death was higher in those without access to ART than in those with access to ART (aHR=9.85, 95%CI: 8.19-11.85). The risk factors for death in those with access to ART included being men (aHR=1.64, 95%CI: 1.29-2.08), age ≥60 years old at diagnosis (aHR=3.52, 95%CI: 2.38-5.20), being infected by injecting drug use/others (aHR=2.38, 95%CI:1.30-4.34), being detected by medical institution (aHR=1.53, 95%CI: 1.11-2.11), CD4+T lymphocytes(CD4) counts <50 cells/µl (aHR=2.58, 95%CI: 1.87-3.58). The protective factor for death was high education level (high school and technical secondary school: aHR=0.64,95%CI:0.46-0.90; college and above: aHR=0.42, 95%CI: 0.24-0.73). The risk factors for HIV/AIDS death in those without access to ART included older age at diagnosis (30-44 years old: aHR=2.32, 95%CI: 1.40-3.84; 45-59 years old:aHR=2.61, 95%CI: 1.59-4.27; ≥60 years old: aHR=3.31, 95%CI: 2.01-5.47), lower CD4 counts (<50 cells/µl: aHR=10.47, 95%CI: 6.47-16.56; 50-199 cells/µl: aHR=2.31, 95%CI: 1.08-4.94; 200-349 cells/µl: aHR=2.35, 95%CI: 1.46-3.79). Conclusions: The case fatality rate of HIV/AIDS was relatively high in Jingzhou from 1996 to 2021, the first CD4 counts, ART and age at diagnosis were the major factors affecting HIV/AIDS death, "Expanding testing" and "prompt treatment upon diagnosis" should be continued and enhanced to improve the efficacy of ART and HIV/AIDS case survival.
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Síndrome de Inmunodeficiencia Adquirida , Instituciones Académicas , Masculino , Humanos , Persona de Mediana Edad , Adulto , Femenino , Estudios Retrospectivos , Escolaridad , AntirretroviralesRESUMEN
Objective: To understand the performance of public health risk assessment in emergencies of institutions for disease control and prevention at different levels in China, and provide suggestions for the improvement of public health risk assessment. Methods: A self-administered survey was conducted in professionals involved in public health risk assessment in emergencies from national institution, provincial institutions and some prefectural institutions for disease control and prevention (1-2 prefectural institutions were selected using convenience sampling in each province) between March and April in 2021. Results: A total of 79 institutions for disease control and prevention were investigated, including 1 national institution, 32 provincial institutions and 46 prefectural institutions. By April 2021, all the 79 institutions surveyed had conducted risk assessment of public health emergencies, in which 61 (77.2%) had established departments responsible for the public health risk assessment, i.e. emergency management office or communicable disease prevention and control office (section), and regular risk assessment mechanisms. The main sources of information for public health risk assessment were public health surveillance systems, including the National Notifiable Diseases Reporting System (100.0%) and Public Health Emergencies Management Information System (97.5%). Compared with the provincial institutions, the prefectural institutions were more likely to use specific disease surveillance systems (84.8% vs. 62.5%; χ2=5.09, P=0.024). The risk management recommendations made by 43 institutions for disease control and prevention (54.4%) after the risk assessment were accepted by the superior health administrative departments and used in epidemic prevention and control. Conclusions: Public health risk assessment in emergencies has been widely carried out by national, provincial and prefectural institutions for disease control and prevention in China. Specialized departments and mechanisms have been established, but the information sources are still confined to public health surveillance systems and the application of the risk assessment results still needs to be further improved.
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Urgencias Médicas , Epidemias , Humanos , Medición de Riesgo , China/epidemiología , Fuentes de InformaciónRESUMEN
OBJECTIVE: Changes in hormone levels, improper lipid metabolism, and oxidative stress all significantly contribute to the pathogenic process of polycystic ovarian syndrome (PCOS). According to earlier research, pioglitazone and alpha-lipoic acid are crucial in the emergence of PCOS. The beneficial effects of pioglitazone and alpha-lipoic acid on PCOS were examined in the current study. PATIENTS AND METHODS: The 120 patients with PCOS received three months of treatment in pioglitazone groups (n=40 case, 30 mg/time, 1 time/day), α-lipoic acid (n=40 case, 0.6 g/time, 1 time/day), and combination therapy (n=40 case, pioglitazone 30 mg/time, 1 time/day and α-lipoic acid, 0.6 g/time, 1 time/day). Before and after therapy, the following factors were evaluated: the hormonal profile, fasting serum insulin, body weight, body mass index (BMI), menstruation status, oxidative stress, and indications of lipid metabolism. RESULTS: The combination of pioglitazone and α-lipoic acid has a significantly improving effect on BMI, body weight, oxidative stress levels, lipid metabolism, and menstrual status. A significant increase in body weight, BMI, and follicle-stimulating hormone (FSH) levels were found in mice after being treated with α-lipoic acid alone. However, the use pioglitazone alone improves body weight, BMI, the calculation of insulin resistance index (HOMA-IR), Area under the curve (AUC)-insulin, fasting glucose/insulin (G/I) ratio, total testosterone, and malondialdehyde (MDA) levels in post-treatment than pre-treatment. CONCLUSIONS: These findings suggest that pioglitazone alone has a better effect than alpha-lipoic acid in improving oxidative stress levels, BMI, and menstrual cyclicity. Additionally, treatment with pioglitazone and alpha-lipoic acid did demonstrate a greater effect than monotherapy with each medication alone.
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Síndrome del Ovario Poliquístico , Ácido Tióctico , Femenino , Humanos , Animales , Ratones , Ácido Tióctico/uso terapéutico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Pioglitazona/uso terapéutico , Peso Corporal , InsulinaRESUMEN
BACKGROUND: The existence and contribution of microglia with senescent-like alterations in the pathogenesis of age-related neurodegenerative diseases like Alzheimer's disease (AD) have been suggested in recent years. However, the identification of this distinct microglial population in vivo has proven challenging, largely due to overlaps in the inflammatory phenotype of activated and senescent microglia. Furthermore, attempts at recapitulating senescence in microglia in vitro are limited. OBJECTIVE: To identify and characterize senescent microglia that occur in vivo in an animal model of neurodegeneration driven by pathologic tau. METHODS: We analyzed the RNA expression patterns of individual microglia from normal mice and the pathogenic tau P301âS PS19 mouse model. We have previously demonstrated that p16-expressing senescent microglia occur in these mice when neurodegeneration has occurred. RESULTS: Here we identify a subset of disease-associated microglia with senescent features, notably characterized by the expression of Ccl4. This signature overlaps with established markers of senescence from other cell types. CONCLUSION: Our characterization of senescent microglia can be used to better understand the role of senescent microglia in various age-related contexts, including whether clearance of senescent microglia represents a viable therapeutic option.
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Enfermedad de Alzheimer , Microglía , Ratones , Animales , Microglía/metabolismo , Enfermedad de Alzheimer/patología , Fenotipo , Modelos Animales de Enfermedad , Ratones TransgénicosRESUMEN
BACKGROUND: Despite the prolonged median disease-free survival (DFS) by adjuvant targeted therapy in non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations, the relationship between the treatment duration and the survival benefits in patients remains unknown. PATIENTS AND METHODS: In this multicenter, randomized, open-label, phase II trial, eligible patients aged 18-75 years with EGFR-mutant, stage II-IIIA lung adenocarcinoma and who had not received adjuvant chemotherapy after complete tumor resection were enrolled from eight centers in China. Patients were randomly assigned (1 : 1) to receive either 1-year or 2-year icotinib (125 mg thrice daily). The primary endpoint was DFS assessed by investigator. The secondary endpoints were overall survival (OS) and safety. This study was registered at ClinicalTrials.gov (NCT01929200). RESULTS: Between September 2013 and October 2018, 109 patients were enrolled (1-year group, n = 55; 2-year group, n = 54). Median DFS was 48.9 months [95% confidence interval (CI) 33.1-70.1 months] in the 2-year group and 32.9 months (95% CI 26.6-44.8 months) in the 1-year group [hazard ratio (HR) 0.51; 95% CI 0.28-0.94; P = 0.0290]. Median OS for patients was 75.8 months [95% CI 64.4 months-not evaluable (NE)] in the 2-year group and NE (95% CI 66.3 months-NE) in the 1-year group (HR 0.34; 95% CI 0.13-0.95; P = 0.0317). Treatment-related adverse events (TRAEs) were observed in 41 of 55 (75%) patients in the 1-year group and in 36 of 54 (67%) patients in the 2-year group. Grade 3-4 TRAEs occurred in 4 of 55 (7%) patients in the 1-year group and in 3 of 54 (6%) patients in the 2-year group. No treatment-related deaths or interstitial lung disease was reported. CONCLUSIONS: Two-year adjuvant icotinib was shown to significantly improve DFS and provide an OS benefit in EGFR-mutant, stage II-IIIA lung adenocarcinoma patients compared with 1-year treatment in this exploratory phase II study.
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Duración de la Terapia , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Receptores ErbB/genéticaRESUMEN
BACKGROUND: Vitamin C is an essential dietary nutrient important for collagen synthesis, including within the gastrointestinal tract. AIM: We aimed to document the prevalence of Vitamin C deficiency (VCD) in patients who present with upper gastrointestinal bleeding (UGIB) and its association with clinical outcomes. METHODS: We conducted a prospective cohort study of patients presenting with UGIB. Fasting Vitamin C levels were collected at admission. Primary outcomes were the prevalence of VCD (Vitamin C level <23 µmol/L, severe VCD < 12 µmol/L) and a composite outcome of adverse events, stratified by VCD status. Secondary outcomes were prolonged hospitalisation and the need for ICU admission. RESULTS: A total of 227 patients were included (mean age 64.5 years, males 63.9%). VCD was identified in 74 (32.6%) and severe deficiency in 32 (14.1%) patients. VCD was associated with a higher composite endpoint of AE (45.9% vs 24.8%, p < 0.01), higher in-hospital mortality (9.5% vs 1.3%, p < 0.01), increased prolonged admissions (62.2% versus 47.1%, p = 0.03) and increased rebleeding (17.6% vs 7.8%, p = 0.03), compared with patients with normal Vitamin C levels. Multivariate logistic regression models showed that VCD was independently associated with the composite endpoint of AE. CONCLUSION: VCD is highly prevalent in patients with UGIB and associated with poorer outcomes, including higher mortality, rebleeding and length of stay. Interventional studies are required to determine the impact of early Vitamin C supplementation on clinical outcomes.
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Deficiencia de Ácido Ascórbico , Hemorragia Gastrointestinal , Masculino , Humanos , Persona de Mediana Edad , Pronóstico , Prevalencia , Estudios Prospectivos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/epidemiología , Deficiencia de Ácido Ascórbico/complicaciones , Deficiencia de Ácido Ascórbico/epidemiología , Ácido Ascórbico/uso terapéuticoRESUMEN
Microglial homeostasis has emerged as a critical mediator of health and disease in the central nervous system. In their neuroprotective role as the predominant immune cells of the brain, microglia surveil the microenvironment for debris and pathogens, while also promoting neurogenesis and performing maintenance on synapses. Chronological ageing, disease onset, or traumatic injury promotes irreparable damage or deregulated signaling to reinforce neurotoxic phenotypes in microglia. These insults may include cellular senescence, a stable growth arrest often accompanied by the production of a distinctive pro-inflammatory secretory phenotype, which may contribute to age- or disease-driven decline in neuronal health and cognition and is a potential novel therapeutic target. Despite this increased scrutiny, unanswered questions remain about what distinguishes senescent microglia and non-senescent microglia reacting to insults occurring in ageing, disease, and injury, and how central the development of senescence is in their pivot from guardian to assailant. To intelligently design future studies to untangle senescent microglia from other primed and reactionary states, specific criteria must be developed that define this population and allow for comparisons between different model systems. Comparing microglial activity seen in homeostasis, ageing, disease, and injury allows for a more coherent understanding of when and how senescent and other harmful microglial subpopulations should be targeted.
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Encéfalo , Microglía , Sistema Nervioso Central , Senescencia CelularRESUMEN
Introduction Several studies have previously been undertaken to investigate the prevalence of radiologic hand osteoarthritis (OA) in Caucasian, Japanese, Chinese, and Arabic populations. To date, there has been no direct international comparison study on the prevalence of radiologic hand OA between a Western and a Southeast Asian population. We hypothesize that there is difference in the pattern of joint involvement among individuals of both populations. Materials and Methods Consecutive hand radiographs from individuals aged 60 years and above were reviewed. Radiographic evidence of osteoarthritis in the various joints in the hands was graded using Kellgren-Lawrence (K-L) score. Chi-square test, Fisher's exact test, or Student's t -test was used as appropriate. Multiple logistic regression analysis was performed to evaluate the associations and relationships of radiographic hand OA between joints. Results A total of 194 patients exhibited radiographic OA. Singaporean patients were more likely to have radiographic OA of the thumb interphalangeal joint (IPJ) (65.1%) compared with the thumb carpometacarpal joint (CMCJ; 40.2%); British patients were more likely to have CMCJ (43.3%) OA than thumb IPJ (21.0%). The difference was statistically significant ( p = 0.00026). In the Singapore population, it was more likely that a patient had concurrent OA of both thumb and finger joints, whereas in the British population, this was apparent in only the above-80-year-old group. The most commonly affected joint was the left thumb IPJ (joint specific prevalence of 35%) in the Singapore population, and the right index finger distal interphalangeal joint (DIPJ; joint specific prevalence of 41.5%) in the British population. Conclusion Our study, the first study to compare between Singaporean and British populations, showed statistically significant difference in the prevalence of OA in the hands. These findings suggest ethnic and cultural factors play a part in such a distribution trend.
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Objective: To provide insight into the diagnosis for clinicians, the clinical characteristics, diagnosis and treatment history of 3 patients with 21-hydroxylase deficiency (21-OHD) and testicular adrenal rest tumors (TART) were analyzed. Methods: The clinical, laboratory and imaging data of 3 male patients with 21-OHD and TART, confirmed with CYP21 gene sequencing, from May 2010 to May 2021 in the First Medical Center of Chinese PLA General Hospital were analyzed retrospectively. The treatment strategy and clinical outcome were followed up. Results: All the 3 patients were first diagnosed with bilateral adrenal mass at the age of 27-42 years old. They were 145-162 cm tall. The levels of progesterone, 17-hydroxyprogesterone, and adrenocorticotropic hormone (ACTH) of the 3 patients were relatively high, and that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) of the 3 patients were low. Testosterone level of 1 patient was significantly elevated, and that of the other 2 patients was below the lower limit of normal range. Testicular ultrasound showed heterogeneous hyperechoic masses in both testes. CT of the adrenal glands showed bilateral adrenal enlargement with mass. All 3 patients were treated with dexamethasone. After 4-96 months of follow-up, 17-hydroxyprogesterone level was kept above the median normal level. One of the patients got married and had a baby after treatment. The sizes of adrenal hyperplasia and testicular masses reduced to various degrees with the change of the testicular masses being proportional to that of adrenal hyperplasia. Conclusions: Patients with 21-OHD are prone to have TART, leading to the impaired testicular function. Early glucocorticold therapy is beneficial to the reduction of TART and restoration of testicular function.
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Hiperplasia Suprarrenal Congénita , Tumor de Resto Suprarrenal , Neoplasias Testiculares , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Tumor de Resto Suprarrenal/diagnóstico , Tumor de Resto Suprarrenal/tratamiento farmacológico , Adulto , Humanos , Lactante , Masculino , Estudios Retrospectivos , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapiaRESUMEN
Recently, accumulating evidence has shown that hydrogen sulphide (H2 S), a newly determined gasotransmitter, plays important roles in senescence, which is an essential biological process for plant fitness and an important agricultural trait that is critical for the yield and quality of farm produce. Here, in this review, we summarize the roles of H2 S in senescence, both before and after the harvesting of agricultural products, and the underlying mechanism is also discussed. During the plant growth process, the function of H2 S in the leaf senescence process has been studied extensively, and H2 S plays roles during the whole process, including the initiation, reorganization and terminal stages. While during the postharvest stage, H2 S can prevents farm products from deterioration resulting from over-ripening, pathogen attack and incorrect storage. The underlying H2 S-related mechanisms during different stages of the senescence process are summarized and compared. The most prominent interaction occurs between H2 S and reactive oxygen species, and the molecular mechanism is explored. Additionally, the conserved action mode of H2 S in different life processes and different species is also discussed. In the future, multi-omics analyses over time will be needed to investigate the detailed mechanisms of H2 S, and a safety attribute analysis of H2 S is also required before it can be used in agricultural production.
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Sulfuro de Hidrógeno , Plantas , Especies Reactivas de OxígenoRESUMEN
Objective: To explore the expression of Runt-related transcription factor 1 (RUNX1) in nasal polyps (NPs) tissues and the potential role on apoptosis of primary human nasal epithelial cells (pHNECs) in NPs. Methods: The expression level of RUNX1 in NPs tissues was determined by Western blot (WB) and immunohistochemical staining (IHC). In vitro, TNF-α (20 ng/ml) was used to stimulate pHNECs to establish the apoptosis injury model. Hoechst staining was performed to observe pHNECs apoptosis by kit. Subsequently, quantitative real-time PCR (qRT-PCR) and WB were utilized to detect the expression of apoptosis-related proteins B-cell lymphoma-2 (BCL-2), BCL2-associated X (BAX) and cysteinyl aspartate specific proteinase-3 (Caspase-3) to assess the level of apoptosis. The plasmid of sh-RUNX1-6 was transfected into the pHNECs apoptosis model, then the effect of RUNX1 silence on apoptosis was evaluated by WB and flow cytometry. Statistical analysis was performed by the SPSS 19.0 and GraphPad Prism5 software. Results: The expression of RUNX1 in NPs tissue was significantly higher than that in inferior turbinates, and the difference was statistically significant (0.274±0.042 vs 0.110±0.027, t=9.675, P<0.05). Compared with the inferior turbinates, BAX and Caspase-3 expressions were increased whereas BCL-2 was decreased in NPs, and the differences were statistically significant (BAX 0.346±0.032 vs 0.302±0.037, Caspase-3 0.228±0.061 vs 0.158±0.065, BCL-2 0.090±0.047 vs 0.276±0.057, t value was 2.680, 2.361 and 7.575, respectively, all P<0.05). The expression levels of RUNX1 and apoptosis in pHNECs increased in a time-dependent manner after TNF-α exposure (P<0.05). Plasmid of sh-RUNX1-6 transfected silenced the expression of RUNX1 in pHNECs treated by TNF-α. After silencing RUNX1 in pHNECs apoptosis model, the protein levels of BAX and Caspase-3 were decreased, while the expression of BCL-2 was increased, the rate of apoptosis was decreased (P<0.05). Conclusions: RUNX1 is increased in NPs. Silencing RUNX1 can inhibit the apoptosis and reduce cell inflammatory damage of pHNECs induced by TNF-α.
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Pólipos Nasales , Apoptosis , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Células Epiteliales , Humanos , Cornetes NasalesRESUMEN
A questionnaire was used to investigate the emergency training needs of novel coronavirus pneumonia of disease prevention and control institutions in provinces, deputy provincial level regions and cities specifically designated in the state plan, and the effect evaluation of emergency training activities conducted by Chinese Center for Disease Control and Prevention (China CDC). The results showed that 67.4% of 47 disease prevention and control institutions (31/46) believed that the emergency training at the initial stage of the epidemic should be conducted as soon as possible, and the form of network training should be given priority. The training should focus on the urgently needed technologies such as epidemiological investigation, formulation and response of prevention and control strategies, laboratory testing, etc. The teaching materials should highlight pertinence and practicability and be presented in the form of electronic video. The average satisfaction score of the video training conducted by China CDC was (8.81±1.125) and the score of audio-video courseware was (8.97±0.893). The needs analysis and evaluation of novel coronavirus pneumonia prevention and control in disease prevention and control institutions could provide reference for the follow-up training and improve the emergency training management.
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COVID-19 , Neumonía , China/epidemiología , Humanos , Neumonía/prevención & control , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
Objective: To analyze the efficacy and safety of Montgomery T-tube (T-tube) placement for benign complex subglottic tracheal stenosis. Methods: A retrospective analysis of the clinical data of 29 patients with benign complex subglottic tracheal stenosis receiving T-tube placement in Beijing Tiantan Hospital from May 2015 to December 2019. The causes were postintubation tracheal stenosis [27 cases (93.1%), including 21 cases (72.4%) of tracheal stenosis after tracheotomy, 6 cases (20.7%) of tracheal stenosis after tracheal intubation], cervical post-traumatic tracheal stenosis (1 case, 3.4%) and tuberculous tracheal stenosis (1 case, 3.4%), respectively. Three-dimensional reconstruction of tracheal computerized tomography (CT) and bronchoscopy were used to grade the stenosis according to Cotton-Myer classification system before bronchoscopic intervention. The degree of stenosis was Cotton-Myer grade â ¡ (7 cases, 24.1%), grade â ¢ (11 cases, 37.9%) and grade â £ (11 cases, 37.9%), respectively. All cases received placement of T-tubes and follow-up. Fisher's exact test was used for comparison between groups. Results: T-tube placement was performed 39 times in 29 patients. T-tubes were successfully placed for 24 cases (82.8%). The main complication during the operation was tracheal mucosal tear (6 cases, 20.7%), which resolved in all cases within 2 weeks. The main postoperative complication was secretion retention (27 cases, 93.1%), which was relieved after home nebulization treatment in 26 cases; and followed by granulation hyperplasia, especially located in T-tube upper margin (12 cases, 41.4%), of which 8 cases were cured after bronchoscopic intervention. None of the patients had T-tube migration. There were no statistically significant differences in the success rate of T-tube placement and the incidence of major complications in patients with benign complex subglottic tracheal stenosis with different degrees of stenosis. After 18 months to 24 months of follow-up, attempt was made to remove the T-tube in 9 patients but failed in 4 patients. The failure was due to collapse of the airway after the T-tube was removed. Conclusion: T-tube placement is a safe and reliable treatment for benign complex subglottic tracheal stenosis with high efficiency and manageable complications.