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To date there are only pirfenidone (PFD) and nintedanib to be given conditional recommendation in idiopathic pulmonary fibrosis (IPF) therapies with slowing disease progression, but neither has prospectively shown a reduced mortality. It is one of the urgent topics to find effective drugs for pulmonary fibrosis in medicine. Previous studies have demonstrated that microcystin-RR (MC-RR) effectively alleviates bleomycin-induced pulmonary fibrosis, but the mechanism has not been fully elucidated yet. We further conducted a comparison of therapeutic effect on the model animals of pulmonary fibrosis between MC-RR and PFD with histopathology and the expression of the molecular markers involved in differentiation, proliferation and metabolism of myofibroblasts, a major effector cell of tissue fibrosis. The levels of the enzyme molecules for maintaining the stability of interstitial structure were also evaluated. Our results showed that MC-RR and PFD effectively alleviated pulmonary fibrosis in model mice with a decreased signaling and marker molecules associated with myofibroblast differentiation and lung fibrotic lesion. In the meantime, both MC-RR and PFD treatment are beneficial to restore molecular dynamics of interstitial tissue and maintain the stability of interstitial architecture. Unexpectedly, MC-RR, rather than PFD, showed a significant effect on inhibiting PKM2-HIF-1α signaling and reducing the level of p-STAT3. Additionally, MC-RR showed a better inhibition effect on FGFR1 expression. Given that PKM2-HIF-1α and activated STAT3 molecular present a critical role in promoting the proliferation of myofibroblasts, MC-RR as a new strategy for IPF treatment has potential advantage over PFD.
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Subunidade alfa do Fator 1 Induzível por Hipóxia , Microcistinas , Fibrose Pulmonar , Piridonas , Animais , Microcistinas/toxicidade , Camundongos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/induzido quimicamente , Piridonas/farmacologia , Piridonas/uso terapêutico , Bleomicina , Transdução de Sinais/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Miofibroblastos/efeitos dos fármacos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Masculino , Modelos Animais de Doenças , Piruvato QuinaseRESUMO
BACKGROUND: Eccrine porocarcinoma (EPC) is a rare skin tumor that mainly affects the elderly population. Tumors often present with slow growth and a good prognosis. EPCs are usually distinguished from other skin tumors using histopathology and immunohistochemistry. However, surgical management alone may be inadequate if the tumor has metastasized. However, currently, surgical resection is the most commonly used treatment modality. CASE SUMMARY: A seventy-four-year-old woman presented with a slow-growing nodule in her left temporal area, with no obvious itching or pain, for more than four months. Histopathological examination showed small columnar and short spindle-shaped cells; thus, basal cell carcinoma was suspected. However, immunohistochemical analysis revealed the expression of cytokeratin 5/6, p63 protein, p16 protein, and Ki-67 antigen (40%), and EPC was taken into consideration. The skin biopsy was repeated, and hematoxylin and eosin staining revealed ductal differentiation in some cells. Finally, the patient was diagnosed with EPC, and Mohs micrographic surgery was performed. We adapted follow-up visits in a year and not found any recurrence of nodules. CONCLUSION: This case report emphasizes the diagnosis and differentiation of EPC.
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Pine wood nematode (PWN) disease is one of the major disasters in forests of southern China, causing substantial forest resources and ecological and economic losses. Based on field surveys and WFV image data from the GF-1 satellite, we constructed a spatial identification model of PWN disease with the random forest model to explore the relative influences of topography, human activities and stand factors on the occurrence of diseases and predict their spatial distribution. We then used the spatial autocorrelation analysis to assess the distribution characteristics of PWN disease at the regional scale. The results showed that the random forest model constructed in this study was effective in identifying pine nematode diseases (AUC value=0.99, overall accuracy=0.96). The norma-lized difference greenness index (NDGI), the distance to the highway, and normalized vegetation index (NDVI) were important factors in explaining the spatial variations of PWN disease occurrence. There was a positive spatial correlation in the occurrence of PWN disease (not randomly distributed but with obvious spatial aggregation characteristics). The high occurrence areas of pine wood nematode disease concentrated in Chitu Township, Zhufang Township and Shibatang Township, low occurrence areas concentrated in the vicinity of Rongjiang Street. The areas far away from the highway, low in elevation, and close to county roads were suffered to PWN disease. The results could serve the regional monitoring of pine nematode disease occurrence and provide practical guidance for PWN disease management.
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Nematoides , Pinus , Tylenchida , Animais , Humanos , Doenças das Plantas , ChinaRESUMO
Objective: Microorganisms have been the main cause of refractory and high recurrence of diabetic foot ulcer (DFU). This study attempted to observe the skin bacterial colony in healthy skin, diabetic skin and DFU skin. Methods: Forty-eight diabetes patients were recruited at Panyu Central Hospital from March 2021 to March 2022 and divided into DFU group (T group, n = 22), diabetes without foot ulcer group (TW group, n = 26). Besides, a healthy control group (H group, n = 10) was recruited at the same time. The swab samples of foot skin in the same position in the three groups were collected. The microorganisms obtained from the skin were analyzed by 16S rRNA gene sequencing. The composition of the skin microorganisms was determined, and the species diversity of the skin microbiota was analyzed by α and ß diversity. The species differences in the skin microbiota and the relative abundance of different operational taxonomic units (OUTs) with the most significant abundance were analyzed by linear discriminant analysis effect size (LEfSe). Results: Significant changes were found in the composition of the skin microbiota in the T and TW groups relative to the H group. However, the species diversity of the skin microbiota was significantly reduced in the T and TW groups, with the lowest one in the T group. The composition of microbial diversity in the T group was significantly different from that of the TW and H groups. Among the skin bacterial colonies, the abundance of Staphylococcus, Enhydrobacter, and Corynebacterium_1 was obviously reduced, while that of Escherichia coli and Pseudomonas was significantly increased. Conclusion: Changes in the abundance of Staphylococcus, Enhydrobacter, Corynebacterium_1, Escherichia coli and Pseudomonas in the skin bacterial colonies can be the main causative factors for DFU. This study indicates that altering the microbiota composition of wounds may help the treatment of DFU.
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Rotavirus remains a major cause of diarrhea among 5-y-old children, and vaccination is currently the most effective and economical measure. We conducted a randomized, double-blind, placebo-controlled phase II clinical trial designed to determine the dosage, immunogenicity, and safety profile of a novel hexavalent rotavirus vaccine. In total, 480 eligible healthy infants, who were 6-12 weeks of age at the time of randomization were randomly allocated (1:1:1) to receive 105.5 focus-forming unit (FFU) or 106.5FFU of vaccine or placebo on a 0, 28 and 56-d schedule. Blood samples were collected 28 d after the third dose to assess rotavirus immunoglobulin A (IgA) antibody levels. Adverse events (AEs) up to 28 d after each dose and serious adverse events (SAEs) up to 6 months after the third dose were recorded as safety measurements. The anti-rotavirus IgA seroconversion rate of the vaccine groups reached more than 70.00%, ranging from 74.63% to 76.87%. The postdose 3 (PD3) geometric mean concentrations (GMCs) of anti-rotavirus IgA among vaccine recipients ranged from 76.97 U/ml to 84.46 U/ml. At least one solicited AE was recorded in 114 infants (71.25%) in the high-dose vaccine group, 106 infants (66.25%) in the low-dose vaccine group and 104 infants (65.00%) in the placebo group. The most frequently solicited AE was fever. The novel oral hexavalent rotavirus vaccine was safe and immunogenic in infants support the conclusion to advance the candidate vaccine for phase 3 efficacy trials.
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Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Humanos , Lactente , Anticorpos Antivirais , Método Duplo-Cego , População do Leste Asiático , Imunogenicidade da Vacina , Imunoglobulina A , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/efeitos adversos , Vacinas contra Rotavirus/uso terapêutico , Vacinas Atenuadas , Vacinas CombinadasRESUMO
OBJECTIVE: To investigate the cytogenetic characteristics and prognostic risk factors for elderly patients with newly diagnosed elderly acute myeloid leukemia(AML). METHODS: Cytogenetic test results of 76 elderly patients with AML admitted to the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital) from April 2015 to December 2021 were retrospectively analyzed, and analyzed clinical characteristics of patients and risk factors influencing prognosis. RESULTS: According to cytogenetic risk stratification, 76 newly treated elderly AML patients were divided into the favorable, intermediate, and unfavorable groups with 6(7.9%), 58(76.3%), and 12(15.8%) cases, respectively. There was no significant difference in the patient's clinical characteristics and prognosis with the cytogenetics-risk classification groups. Correlation analysis showed that patients' objective response rate (ORR) was related to the age of onset and the mutation status of the CEBPA gene. Logistic regression analysis found that age ≥70 years was an independent risk factor for patients' ORR (OR=0.110, P=0.005). Remission determined the 1-year OS rate (OR=0.049, P=0.005). CONCLUSION: There is no significant difference in clinical characteristics among aged AML patients treated at initial treatment in different cytogenetic risk groups. The age of onset ≥70 years is the determinant of whether patients can obtain ORR, and the rate of ORR is closely related to the 1-year OS rate.
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Background: Esophagogastric junctional squamous cell carcinoma (EJSCC) is quite rare among all gastric carcinoma, its potential resectable rate is low due to the late diagnosis. Recently, programmed death-1 (PD-1) blockade combined with anti-angiogenesis have gained accumulated clinical experiences in treating solid tumors. This is the first reported case with EJSCC who achieved a partial remission (PR) after neoadjuvant PD-1 blockade, vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor plus chemotherapy. Case Description: We present an EJSCC case treated with novel neoadjuvant treatment. A 64-year-old Chinese male had the symptom of chocking for 3 months. An enhanced abdominal computed tomography (CT) scan found a locally advanced, potentially unresectable esophagogastric junctional (EGJ) mass, and the preoperative immunohistochemistry result exhibited a highly positive programmed death-ligand 1 (PD-L1) expression, so the patient received three courses of neoadjuvant camrelizumab (200 mg/day), apatinib (750 mg/day), albumin paclitaxel (200 mg/day) and nedaplatin (70 mg/day), he was well tolerant without any adverse event, and he underwent radical surgery after a significant tumor shrinkage. The patient recovered well after surgery, and he has received four cycles of camrelizumab and apatinib as maintenance treatment. There is no recurrence 7 months after surgery. Conclusions: PD-1 blockade, VEGFR-2 inhibitor plus chemotherapy is effective and safe for the patient with EJSCC.
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Pine wilt disease has caused huge losses in ecological and economic values in China, especially in the southern parts. Analyzing the spatial distribution of pine wilt disease and quantifying the impact of environmental factors on its occurrence were of great significance for its prevention and control. In this study, we examined the spatial pattern of pine wilt disease occurrence and its response to environmental variables in Nankang District, Ganzhou, Jiangxi Province, using kernel-smoothing density, Ripley's K function, and point process model. The results showed that the occurrence of pine wilt disease in the study region was not randomly distributed, but was obviously clustered at some areas. Terrain, vegetation, and human activity were the main factors affecting the heterogeneous distribution of pine wilt disease. Spatial point pattern analysis showed that altitude, slope, distance to the nearest road, road density, distance to nearest settlement, canopy closure, and vegetation type had significant effects on the occurrence of pine wilt disease. In addition to strengthening the control of disease transmission caused by human activities, we should also consider the effects of terrain and vegetation types for early warning and monitoring in forest disease management.
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Pinus , China/epidemiologia , Humanos , Análise EspacialRESUMO
Aortoesophageal fistula (AEF), secondary to thoracic pseudoaneurysm as a result of upper gastrointestinal bleeding, is a rare condition and will be undoubtedly lethal without prompt surgical intervention. The estimated annual incidence of primary AEFs and secondary AEFs is about 0.0015% and 0.6%-2%, respectively. The challenges of the therapy posed by AEF are control of the hemorrhage, arterial reconstruction in an infection field, control of sepsis, and re-establishment of the alimentary tract. We present a case of a 58-year-old man who suffered from chest pain and hematemesis and was finally diagnosed with pAEF caused by descending thoracic pseudoaneurysm. Our team successfully deployed an endovascular stent graft and esophageal stent to seal ruptured thoracic aorta and esophageal defects, which provided a new surgical strategy for aortoesophageal fistula in the endovascular era.
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The distribution pattern of forest fuel loading is driven by the interaction of environmental factors, such as terrain and vegetation. Based on field sampling data of surface dead fuels of seven main forest types in southern Jiangxi Province, and according to the classification standard of different time-lags, we constructed structural equation models to explore the relationship between surface fuel loadings and environmental factors such as terrain and vegetation etc. We analyzed the influence path of each factor and its direct, indirect, and total influence. The results showed that the coniferous and broad-leaved mixed forest had the highest loadings and the Phyllostachys heterocycla pure forest had the lowest loadings for all the 1, 10, and 100 h time-lag fuels. The influencing coefficient of environmental factors for 1 h time-lag fuels were ranked as: slope (0.40) > crown height (0.07) > tree species (-0.03) > canopy closure (0.01). For the 10 h time-lag fuels, the environmental factors were ranked as: diameter at breast height (0.15) >tree species (-0.09) > aspect (-0.08) > canopy closure (-0.06). For the 100 h time-lag fuels, the environmental factors were ranked as: aspect (0.25) > diameter at breast height (0.19) > canopy closure (-0.08) > tree species (0.02). The influencing coefficient of environmental factors for the total fuels were ranked as: slope (0.22) > tree species (-0.04), canopy closure (-0.04) > crown height (-0.01).
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Florestas , Traqueófitas , China , Modelos Teóricos , ÁrvoresRESUMO
BACKGROUND: Delayed gastric emptying (DGE) after distal gastrectomy impacts patients' nutritional status and quality of life. The current treatments of DGE seem unsatisfactory or need invasive interventions. It is unknown whether transcutaneous electroacupuncture (TEA) is effective in treating DGE. METHODS: A total of 90 eligible participants who underwent distal gastrectomy will be randomly allocated to either the TEA group (n = 60) or the sham transcutaneous electroacupuncture (sham-TEA) group (n = 30). Each participant will receive TEA on the bilateral acupoints of Zusanli (ST36) and Neiguan (PC6) for 4 weeks. The primary outcomes will be the residual rates of radioactivity in the stomach by gastric scintigraphy and total response rates. The secondary outcomes will be endoscopic features, autonomic function, nutritional and psychological status, serum examination, and quality of life (QoL). The adverse events will also be reported. The patients will be followed up 1 year after the treatment. DISCUSSION: The findings of this randomized trial will provide high-quality evidence regarding the efficacy and safety of long-term TEA for treating DGE after distal gastrectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033965. Registered on 20 June 2020.
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Eletroacupuntura , Gastroparesia , Pontos de Acupuntura , Eletroacupuntura/efeitos adversos , Gastrectomia/efeitos adversos , Gastroparesia/etiologia , Gastroparesia/terapia , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
OBJECTIVE: Angelica (A.) sinensis is used as a traditional medical herb for the treatment of neurodegeneration, aging, and inflammation in Asia. A. sinensis optimal formula (AOF) is the best combination in A. sinensis that has been screened to rescue the cognitive ability in ß-amyloid peptide (Aß25-35)-treated Alzheimer's disease (AD) rats. The objective of this study was to investigate the effect of AOF on the learning and memory of AD rats as well as to explore the underlying mechanisms. METHODS: Male Wistar rats were infused with Aß25-35 for AD model induction or saline (negative control). Five groups of AD rats were fed on AOF at 20, 40, or 80 mL/kg every day, donepezil at 0.9 mg/kg every day (positive control), or an equal volume of water (AD model) intragastrically once a day for 4 weeks, while the negative control rats were fed on water. The Morris water maze test was used to evaluate the cognitive function of the rats. The Aß accumulation, cholinergic levels, and antioxidative ability were detected by ELISA. Additionally, the candidate mechanism was determined by gene sequencing and quantitative real-time polymerase chain reaction. RESULTS: The results showed that AOF administration significantly ameliorated Aß25-35-induced memory impairment. AOF decreased the levels of amyloid-ß precursor protein and Aß in the hippocampus, rescued the cholinergic levels, increased the activity of superoxide dismutase, and decreased the malondialdehyde level. In addition, AOF inhibited the expression of IL1b, Mpo, and Prkcg in the hippocampus. CONCLUSION: These experimental findings illustrate that AOF prevents the decrease in cognitive function and Aß deposits in Aß25-35-treated rats via modulating neuroinflammation and oxidative stress, thus highlighting a potential therapeutic avenue to promote the co-administration of formulas that act on different nodes to maximize beneficial effects and minimize negative side effects.
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Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/farmacologia , Angelica sinensis , Transtornos da Memória/tratamento farmacológico , Doenças Neuroinflamatórias/tratamento farmacológico , Nootrópicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Preparações de Plantas/farmacologia , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/imunologia , Doença de Alzheimer/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/imunologia , Transtornos da Memória/metabolismo , Doenças Neuroinflamatórias/induzido quimicamente , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/metabolismo , Nootrópicos/administração & dosagem , Preparações de Plantas/administração & dosagem , Ratos , Ratos WistarRESUMO
OBJECTIVE: Accumulating evidence has demonstrated that the pathophysiology of schizophrenia is involved in various abnormalities in oxidative stress markers and cytokines closely related to synaptic plasticity. However, the interactive effects among key cytokines, oxidative stress, and executive dysfunction and symptoms of schizophrenia have not been investigated yet. METHODS: A total of 189 patients with chronic schizophrenia and 60 controls were recruited in the current study. Tumor necrosis factor α (TNF-α), interleukin (IL)-8, IL-6, and IL-2 levels; catalase, glutathione peroxidase, and superoxide dismutase (SOD) activities; and malondialdehyde (MDA) levels were determined in patients and controls. Executive function was evaluated by the Wisconsin card sorting tests, the verbal fluency tests, and the Stroop word-color test. Clinical symptoms were evaluated by the Positive and Negative Syndrome Scale. RESULTS: Relative to the controls, the patients had lower activities of SOD and glutathione peroxidase and levels of TNF-α, but higher levels of MDA, IL-8, IL-6, and IL-2 (all p values < .05). A significant negative relationship between SOD activity and IL-8 levels was found only in patients (ß = -0.44, p = .008). Furthermore, we found that an interactive effect of low TNF-α level and high MDA level was associated with negative symptoms (ß = -0.02, p = .01). Moreover, the interactive effects of IL-8 and MDA or IL-8 and SOD were correlated with executive function only in patients (ß = 0.23, p = .02; ß = 0.09, p = .03). CONCLUSIONS: Our findings suggest that the interrelationships between oxidative stress markers and cytokines occur in schizophrenia patients, which may be the basis of their pathological mechanisms underlying clinical symptoms and cognitive dysfunction.
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Esquizofrenia , Citocinas , Função Executiva , Humanos , Malondialdeído , Estresse Oxidativo , Superóxido DismutaseRESUMO
BACKGROUND: MET fusion is a key driver mutation, but it is rare in gastric cancer (GC). Several MET (hepatocyte growth factor receptor) inhibitors have been approved for the treatment of MET-positive patients, but the tumor response is heterogeneous. With the development of next-generation sequencing, diverse MET fusion partner genes have been identified. We herein report a fusion variant involving KIF5B-MET in GC. CASE SUMMARY: After thoracoscopic inferior lobectomy plus lymph node dissection under general anesthesia, a "tumor within a tumor" was found in the lung tumor tissue of a 64-year-old non-smoking male patient. Combining the medical history and the results of enzyme labeling, the focal area was considered to be GC. To seek potential therapeutic regimens, an intergenic region between KIF5B and MET fusion was identified. This fusion contains a MET kinase domain and coil-coiled domains encoded by KIF5B exons 1-25, which might drive the oncogenesis. CONCLUSION: Our finding could extend the spectrum and genomic landscape of MET fusions in GC and favor the development of personalized therapy.
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Sarcomatoid malignant mesothelioma (MM) is a rare and aggressive disease, and its diagnosis is challenging. A 60-year-old man presented with a recurrent subcutaneous mass in his right back after the initial resection. A chest computed tomography (CT) scan found right pleural thickening, nodular pleural thickening, pleural effusion, mediastinal, and right infraclavicular lymph nodes enlargement, which indicated a right pleura MM. Immunohistochemical stains of the resected mass showed sarcomatous atypical spindle cells, which were positive for pan-CKs (clone Anti-cytokeratin cocktail AE1/AE3), cytokeratin 5/6 (CK5/6), Wilm's tumor 1, podoplanin, vimentin and programmed death-ligand 1 (PD-L1), and negative for Napsin A, thyroid transcription factor 1, CDX 2, calretinin and desmin, and fluorescent in situ hybridization detected homozygous p16/cyclin-dependent kinase inhibitor 2A (p16/CDKN2A) deletion. The association of the chest CT features and the pathological assessment confirmed metastatic MM in the subcutaneous layer of the back. Moreover, positron emission tomography-CT showed multiple metastases in his brain. He developed massive right pleural effusion and chest tightness soon, and the mass kept growing despite local and systemic treatments. The patient die of pulmonary failure in 3 months.
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Mesotelioma Maligno/diagnóstico , Neoplasias Pleurais/patologia , Insuficiência Respiratória/etiologia , Neoplasias Cutâneas/diagnóstico , Tela Subcutânea/patologia , Dorso , Biomarcadores Tumorais/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Evolução Fatal , Deleção de Genes , Humanos , Imageamento por Ressonância Magnética , Masculino , Mesotelioma Maligno/complicações , Mesotelioma Maligno/genética , Mesotelioma Maligno/secundário , Pessoa de Meia-Idade , Pleura/diagnóstico por imagem , Pleura/patologia , Neoplasias Pleurais/complicações , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/genética , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/secundário , Tela Subcutânea/diagnóstico por imagemRESUMO
Background Rotavirus infections, prevalent in human populations, are caused mostly by group A viruses. Immunization against rotaviruses in infancy is currently the most effective and economical strategy to prevent rotavirus infection. This study evaluated the safety of a novel hexavalent rotavirus vaccine and analyzed its dose and immunogenicity.Methods This randomized, double-blinded, placebo-controlled phase I clinical trial enrolled healthy adults, toddlers, and infants in Zhengding County, Hebei Province, northern China. 40 adults and 40 children were assigned in a 2:1:1 ratio to receive one vaccine dose, placebo 1, and placebo 2, respectively. 120 6-12 week old infants were assigned equivalently into 3 groups. The infants in each group were assigned in a 2:1:1 ratio to receive three doses of vaccine, placebo 1, and placebo 2, at a 28-day interval. Adverse events (AEs) until 28 days after each dose and serious adverse events (SAEs) until 6 months after the third dose were reported. Virus shedding until 14 days after each dose in infants was tested. Geometric mean concentrations (GMCs) and seroconversion rates were measured for anti-rotavirus IgA by using an enzyme-linked immunosorbent assay (ELISA).Results The solicited and unsolicited AE frequencies and laboratory indexes were similar among the treatment groups. No vaccine-related SAEs were reported. The average percentage of rotavirus vaccine shedding in the infant vaccine groups was 5.00%. The post-3rd dose anti-rotavirus IgA antibody geometric mean concentrations (GMC) and seroconversion rate were higher in the vaccine groups than in the placebo groups.Conclusions The novel oral hexavalent rotavirus vaccine was generally well-tolerated in all adults, toddlers and infants, and the vaccine was immunogenic in infants.
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Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Adulto , Anticorpos Antivirais , China , Método Duplo-Cego , Humanos , Imunogenicidade da Vacina , Lactente , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/efeitos adversos , Vacinas Atenuadas/efeitos adversos , Vacinas CombinadasRESUMO
BACKGROUND: Patients with antipsychotic-naïve first-episode (ANFE) schizophrenia (SZ) can help clarify many confounding factors in determining sex differences in antipsychotic drug induced weight gain and its association with symptom improvement. METHODS: This 8-week longitudinal trial of ANFE patients with SZ enrolled 526 patients and 313 healthy controls. We evaluated bodyweight and the efficacy of antipsychotics on the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 8. RESULTS: Males and females after treatment showed no sex difference in weight gain, BMI increase, and percentage of weight gain. However, at baseline, male patients had more positive symptoms than female patients, and decreases in positive symptoms, general psychopathology, and total PANSS scores were less in male than female patients. Adjusting for confounding factors using multiple linear regression confirmed that weight gain was significantly associated with these decreases in PANSS symptoms only in men not women. CONCLUSIONS: The relationship between weight gain and symptom reduction after 8 weeks of antipsychotic treatment exists only in male patients with ANFE SZ and not in female patients.
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Antipsicóticos , Esquizofrenia , Antipsicóticos/efeitos adversos , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Esquizofrenia/tratamento farmacológico , Aumento de PesoRESUMO
Ribosome assembly factor URB1 is essential for ribosome biogenesis. However, its latent role in cancer remains unclear. Analysis of The Cancer Genome Atlas database and clinical tissue microarray staining showed that URB1 expression was upregulated in colorectal cancer (CRC) and prominently related to clinicopathological characteristics. Silencing of URB1 hampered human CRC cell proliferation and growth in vitro and in vivo. Microarray screening, ingenuity pathway analysis, and JASPAR assessment indicated that activating transcription factor 4 (ATF4) and X-box binding protein 1 (XBP1) are potential downstream targets of URB1 and could transcriptionally interact through direct binding. Silencing of URB1 significantly decreased ATF4 and cyclin A2 (CCNA2) expression in vivo and in vitro. Restoration of ATF4 effectively reversed the malignant proliferation phenotype of URB1-silenced CRC cells. Dual-luciferase reporter and ChIP assays indicated that XBP1 transcriptionally activated ATF4 by binding with its promoter region. X-box binding protein 1 colocalized with ATF4 in the nuclei of RKO cells, and ATF4 mRNA expression was positively regulated by XBP1. This study shows that URB1 contributes to oncogenesis and CRC growth through XBP1-mediated transcriptional activation of ATF4. Therefore, URB1 could be a potential therapeutic target for CRC.
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Fator 4 Ativador da Transcrição/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Proteínas Nucleares/genética , Ribossomos/genética , Ativação Transcricional/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/genética , Regulação para Cima/genética , Proteína 1 de Ligação a X-Box/genéticaRESUMO
Abnormal brain-derived neurotrophic factor (BDNF) levels are involved in cognitive decline in patients with schizophrenia. The role of atypical antipsychotic risperidone in improving cognitive function remains unclear. The study aimed to investigate the effect of risperidone monotherapy on cognitive impairment in drug-naïve first-episode (DNFE) patients with schizophrenia and whether BDNF levels were correlated to the improvement of cognition. 354 DNFE patients and 152 healthy controls were recruited, and we compared their serum BDNF levels and cognition shown on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). High and low BDNF subgroups were defined by median split. Then, 211 patients were treated with risperidone monotherapy for 12 weeks, and their serum BDNF levels and cognition were measured again after treatment. DNFE patients had poorer cognitive functions and lower BDNF levels compared to controls. Lower BDNF levels were correlated with delayed memory in DNFE patients with high baseline BDNF levels. After 12 weeks of treatment, risperidone significantly improved immediate memory, delayed memory and RBANS total scores and BDNF levels were slightly increased. In patients with low-BDNF, BDNF levels were significantly increased after risperidone treatment, while in patients with high-BDNF, BDNF levels were significantly decreased. In addition, baseline BDNF levels were associated with improvement of delayed memory and were a prognostic factor for the improvement of the delayed memory and RBANS total score in patients with high-BDNF. Our result suggests risperidone treatment can partially improve certain domains of the cognitive impairment and baseline BDNF levels are related to cognitive response to risperidone in DNFE patients with schizophrenia.
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Fator Neurotrófico Derivado do Encéfalo/análise , Cognição/fisiologia , Esquizofrenia/metabolismo , Adulto , Antipsicóticos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/sangue , Transtornos Cognitivos/tratamento farmacológico , Disfunção Cognitiva/sangue , Feminino , Humanos , Estudos Longitudinais , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Estudos Prospectivos , Risperidona/uso terapêutico , Esquizofrenia/sangueRESUMO
A tetrahedral DNA probe can effectively overcome the steric effects of a single-stranded probe to obtain well-controlled density and minimize nonspecific adsorption. Herein, a highly sensitive electrochemical biosensor is fabricated for determination of protein using a tetrahedral DNA probe and rolling circle amplification (RCA). N- and P-co-doped graphene (NP-rGO) is prepared, and AuNPs are then electrodeposited on it for DNA probe immobilization. Benefitting from the synergistic effects of the excellent electrical conductivity of NP-rGO, the stability of the tetrahedral DNA probe and the signal amplification of RCA, the biosensor achieves a low limit of 3.53 × 10-14 M for thrombin and a wide linear range from 1 × 10-13 to 1 × 10-7 M. This study provides a sensitive and effective method for the detection of protein in peripheral biofluids, and paves the way for future clinical diagnostics and treatment of disease. Graphical abstract.