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Background: Severe fever with thrombocytopenia syndrome (SFTS) is spreading rapidly in Asia. The pathway of SFTS virus shedding from patient and specific use of personal protective equipments (PPEs) against viral transmission have rarely been reported. The study was to determine SFTS virus (SFTSV) shedding pattern from the respiratory, digestive and urinary tract to outside in patients. Methods: Patients were divided into mild and severe groups in three sentinel hospitals for SFTS in Anhui province from April 2020 to October 2022. SFTSV level from blood, throat swabs, fecal/anal swabs, urine and bedside environment swabs of SFTS patients were detected by qRT-PCR. Specific PPEs were applied in healthcare workers contacting with the patients who had oropharyngeal virus shedding and hemorrhagic signs. Results: A total of 189 SFTSV-confirmed patients were included in the study, 54 patients died (case fatality rate, 28.57 %). Positive SFTSV in throat swabs (T-SFTSV), fecal/anal swabs (F-SFTSV) and urine (U-SFTSV) were detected in 121 (64.02 %), 91 (48.15 %) and 65 (34.4 %) severely ill patients, respectively. The levels of T-SFTSV, F-SFTSV and U-SFTSV were positively correlated with the load of SFTSV in blood. We firstly revealed that SFTSV positive rate of throat swabs were correlated with occurrence of pneumonia and case fatality rate of patients (P < 0.0001). Specific precaution measures were applied by healthcare workers in participating cardiopulmonary resuscitation and orotracheal intubation for severely ill patients with positive T-SFTSV, no event of SFTSV human-to-human transmission occurred after application of effective PPEs. Conclusions: Our research demonstrated SFTSV could shed out from blood, oropharynx, feces and urine in severely ill patients. The excretion of SFTSV from these parts was positively correlated with viral load in the blood. Effective prevention measures against SFTSV human-to-human transmission are needed.
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Spinocerebellar ataxia is a phenotypically and genetically heterogeneous group of autosomal dominant-inherited degenerative disorders. The gene mutation spectrum includes dynamic expansions, point mutations, duplications, insertions, and deletions of varying lengths. Dynamic expansion is the most common form of mutation. Mutations often result in indistinguishable clinical phenotypes, thus requiring validation using multiple genetic testing techniques. Depending on the type of mutation, the pathogenesis may involve proteotoxicity, RNA toxicity, or protein loss-of-function. All of which may disrupt a range of cellular processes, such as impaired protein quality control pathways, ion channel dysfunction, mitochondrial dysfunction, transcriptional dysregulation, DNA damage, loss of nuclear integrity, and ultimately, impairment of neuronal function and integrity which causes diseases. Many disease-modifying therapies, such as gene editing technology, RNA interference, antisense oligonucleotides, stem cell technology, and pharmacological therapies are currently under clinical trials. However, the development of curative approaches for genetic diseases remains a global challenge, beset by technical, ethical, and other challenges. Therefore, the study of the pathogenesis of spinocerebellar ataxia is of great importance for the sustained development of disease-modifying molecular therapies.
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BACKGROUND: The mucosal barrier's immune-brain interactions, pivotal for neural development and function, are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome (IBS). Prior studies linking immune inflammation with IBS have been inconsistent. To further elucidate this relationship, we conducted a Mendelian randomization (MR) analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS. Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets. AIM: To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS. We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies. METHODS: We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS. By utilizing genetic data from public databases, we examined the causal associations between 731 immune cell markers, encompassing median fluorescence intensity, relative cell abundance, absolute cell count, and morphological parameters, with IBS susceptibility. Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy. RESULTS: Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes. However, our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes (P < 0.05). Nine immune phenotypes demonstrated a protective effect against IBS [inverse variance weighting (IVW) < 0.05, odd ratio (OR) < 1], while 21 others were associated with an increased risk of IBS onset (IVW ≥ 0.05, OR ≥ 1). CONCLUSION: Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS, providing valuable insights into the pathophysiology of the condition. These results pave the way for the development of more precise biomarkers and targeted therapies for IBS. Furthermore, this research enriches our comprehension of immune cell roles in IBS pathogenesis, offering a foundation for more effective, personalized treatment approaches. These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.
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Herein, the first F-containing iodate-phosphate, namely Ba2Ga2F6(IO3)(PO4), was prepared via a hydrothermal reaction, in which HPF6 (70 wt% solution in water) was used as the source of both fluoride and phosphate anions for the first time. Ba2Ga2F6(IO3)(PO4) features an unprecedented 1D [Ga2F6(IO3)(PO4)]4- helix chain, composed of a 1D Ga(1)(IO3)O4F chain via the bridging of 0D Ga(2)(PO4)F5. The UV-Vis spectrum shows that Ba2Ga2F6(IO3)(PO4) has a wide bandgap with a short-UV absorption edge (4.35 eV; 253 nm). Birefringence measurement under a polarizing microscope shows that Ba2Ga2F6(IO3)(PO4) displays a moderate birefringence of 0.072@550 nm, which is consistent with the value (0.070@550 nm) obtained by DFT calculations, indicating that Ba2Ga2F6(IO3)(PO4) has potential applications as a short-UV birefringent material. This study highlights the crucial role played by the incorporation of specific functional groups into compounds, shedding light on their contribution to promising inorganic functional materials.
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OBJECTIVE: To analyze the characteristics and prognosis of patients with mucormycosis after chemotherapy for acute leukemia, and to strengthen understanding of the disease. METHODS: 7 cases of acute leukemia (AL) patients diagnosed with mucormycosis by metagenomic next generation sequencing (mNGS) after chemotherapy at the First Affiliated Hospital of Bengbu Medical College from October 2021 to June 2022 were collected, and their clinical data, including clinical characteristics, diagnosis, treatment, and prognosis, were retrospectively analyzed. RESULTS: Among the 7 patients with AL complicated with mucormycosis, there were 3 males and 4 females, with a median age of 52(20-59) years. There were 6 cases of acute myeloid leukemia (AML) and 1 case of acute lymphocytic leukemia (ALL). Extrapulmonary involvement in 4 cases, including 1 case suspected of central nervous system involvement. The median time for the occurrence of mucor infection was 16(6-69) days after chemotherapy and 19(14-154) days after agranulocytosis. The main clinical manifestations of mucormycosis were fever (7/7), cough (3/7), chest pain (3/7) and dyspnea (1/7). The most common chest CT imaging findings were nodules, patchy or mass consolidation (6/7). All patients were treated with posaconazole or voriconazole prophylaxis during neutropenia phase. 5 patients died within 8 months, and the median time from diagnosis to death was 1 month. CONCLUSION: Although prophylactic antifungal therapy is adopted, patients with acute leukemia still have a risk of mucor infection during the neutropenia phase. Fever is the main manifestation in the early stage of mucor infection. The use of intravenous antifungal drugs alone is ineffective and there is a high mortality rate in acute leukemia patients with mucormycosis.
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Leucemia Mieloide Aguda , Mucormicose , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Mucormicose/diagnóstico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antifúngicos/uso terapêutico , Adulto Jovem , Leucemia/complicações , Leucemia/tratamento farmacológicoRESUMO
Background: It has been suggested in several observational studies that migraines are associated with the gut microbiota. It remains unclear, however, how the gut microbiota and migraines are causally related. Methods: We performed a bidirectional two-sample mendelian randomization study. Genome-wide association study (GWAS) summary statistics for the gut microbiota were obtained from the MiBioGen consortium (n = 18,340) and the Dutch Microbiota Project (n = 7,738). Pooled GWAS data for plasma metabolites were obtained from four different human metabolomics studies. GWAS summary data for migraine (cases = 48,975; controls = 450,381) were sourced from the International Headache Genetics Consortium. We used inverse-variance weighting as the primary analysis. Multiple sensitivity analyses were performed to ensure the robustness of the estimated results. We also conducted reverse mendelian randomization when a causal relationship between exposure and migraine was found. Results: LachnospiraceaeUCG001 (OR = 1.12, 95% CI: 1.05-1.20) was a risk factor for migraine. Blautia (OR = 0.93, 95% CI: 0.88-0.99), Eubacterium (nodatum group; OR = 0.94, 95% CI: 0.90-0.98), and Bacteroides fragilis (OR = 0.97, 95% CI: 0.94-1.00) may have a suggestive association with a lower migraine risk. Functional pathways of methionine synthesis (OR = 0.89, 95% CI: 0.83-0.95) associated with microbiota abundance and plasma hydrocinnamate (OR = 0.85, 95% CI: 0.73-1.00), which are downstream metabolites of Blautia and Bacteroides fragilis, respectively, may also be associated with lower migraine risk. No causal association between migraine and the gut microbiota or metabolites was found in reverse mendelian randomization analysis. Both significant horizontal pleiotropy and significant heterogeneity were not clearly identified. Conclusion: This Mendelian randomization analysis showed that LachnospiraceaeUCG001 was associated with an increased risk of migraine, while some bacteria in the gut microbiota may reduce migraine risk. These findings provide a reference for a deeper comprehension of the role of the gut-brain axis in migraine as well as possible targets for treatment interventions.
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OBJECTIVE: To detect the expression of RNA methyltransferase 14(METTL14) in bone marrow of patients with newly diagnosed acute myeloid leukemia (AML), and to investigate the clinical and prognostic significance of METTL14 expression in newly diagnosed AML. METHODS: Bone marrow samples were collected from 100 patients with newly diagnosed AML as observation group and 60 patients with iron deficiency anemia AML as control group. And collected the clinical data of the AML patients. Real-time quantitative PCR (qRT-PCR) was used to detect the expression level of METTL14 in AML and IDA patients. The relationship between the expression level of METTL14 and clinicopathological features, prognosis was analyzed. Kaplan-Meier curves were used to analyze the effect of METTL14 on overall survival (OS) in AML patients. Cox risk regression model was used to analyze the prognostic factors affecting in patients with AML. RESULTS: Compared with the control group, the expression of METTL14 was significantly increased in AML patients (P < 0.05). Compared with the METTL14 low-expression group, patients in the METTL14 high-expression group had advanced age, high bone marrow cell number, poor efficacyand poor prognosis(P < 0.05). The overall survival time of patients with the METTL14 high-expression group was significantly shorter than that of the low-expression group (P < 0.05). The high expression of METTL14 was an independent risk factor for poor prognosis in AML. CONCLUSION: METTL14 is significantly overexpressed in AML patients, and its correlated with poor clinicopathological features and poor prognosis. It can be used as a prognostic marker and potential therapeutie target for AML patients.
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Leucemia Mieloide Aguda , Metiltransferases , Humanos , Leucemia Mieloide Aguda/genética , Metiltransferases/metabolismo , Metiltransferases/genética , Prognóstico , Medula Óssea/metabolismo , Masculino , Feminino , Relevância ClínicaRESUMO
As a well-known classical Chinese medicine prescription, Shengxian Decoction (SXD) has been applied for a century to treat cardiovascular diseases, especially coronary heart disease (CHD), but the potentially effective compounds and underlying mechanisms remain unclear. With ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) and network pharmacology analysis, the potential effective compounds of SXD and their pharmacological mechanisms against CHD were identified and revealed. 57 effective compounds with favorable pharmacokinetic characteristics and biological activities were screened through UPLC-Q-TOF/MS analysis, database and literature mining, interacting with 96 CHD-related targets to support potential synergistic therapeutic actions. Systematic analysis of the PPI network and microarray data further revealed six core targets, including TNF, IL-1ß, IL-6, TP53, VEGFA and PTGS2, which were mainly involved in fluid shear stress and atherosclerosis, lipid and atherosclerosis, PI3K-Akt signaling pathway et al. Moreover, the proposed contribution indexes of effective compounds indicated these compounds, including isoferulic acid, quercetin, calycosin, ferulic acid, kaempferol, calycosin 7-O-glycoside, formononetin, astragaloside IV and saikosaponin D, as the core compounds of SXD. The molecular docking results confirmed that those core compound-target pairs exhibited strong binding energy. Furthermore, we validated that SXD significantly alleviated myocardial tissue injury in CHD rats and reversed H/R-induced decreases in H9c2 cell viability by attenuating the production of TNF, IL-6 and IL-1ß, and reducing cardiomyocyte apoptosis via down-regulating the TP53, caspase3 and cytochrome C mRNA expression levels as well as caspase3, caspase9 and cytochrome C protein expression levels according to RT-qPCR and Western blot results. Our findings explained the pharmacological mechanisms underlying the effectiveness of SXD in the treatment of CHD, and laid a foundation for future basic and clinical research of SXD.
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The detection of ascorbic acid (AA), dopamine (DA), and uric acid (UA) is not only of great significance in the areas of biomedicine and neurochemistry but also helpful in disease diagnosis and pathology research. Due to their diverse structures, designability, and large specific surface areas, metal-organic frameworks (MOFs) have recently caught considerable attention in the electrochemical field. Herein, a family of heterometallic MOFs with amino modification, MIL-125(Ti-Al)-xNH2 (x = 0%, 25%, 50%, 75%, and 100%), were synthesized and employed as electrochemical sensors for the detection of AA, DA, and UA. Among them, MIL-125(Ti-Al)-75%NH2 exhibited the most promising electrochemical behavior with 40% doping of carbon black in 0.1 M PBS (pH = 7.10), which displayed individual detection performance with wide linear detection ranges (1.0-6.5 mM for AA, 5-100 µM for DA and 5-120 µM for UA) and low limits of detection (0.215 mM for AA, 0.086 µM for DA, and 0.876 µM for UA, S/N = 3). Furthermore, the as-prepared MIL-125(Ti-Al)-75%NH2/GCE provided a promising platform for future application in real sample analysis, owing to its excellent anti-interference performance and good stability.
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Dopamina , Estruturas Metalorgânicas , Dopamina/análise , Ácido Úrico/análise , Ácido Ascórbico/química , Eletrodos , Titânio , Técnicas EletroquímicasRESUMO
To understand the water pollution status and environmental risks of Changshou Lake, the concentrations of heavy metals (Cr, Cu, Zn, As, Cd, and Pb) in the water were collected and analyzed during different seasons. The study investigated temporal and spatial variations, distribution characteristics, pollution levels, and health risks associated with heavy metals in Changshou Lake. The results showed that all six heavy metals were below than the Class â standard of the Surface Water Environmental Quality Standard (GB 3838-2002), but recent years have witnessed an increasing trend, with Cu, As, and Pb showing a significant increase (P<0.05). The temporal and spatial distributions of these heavy metals were different. Temporally, Cr and Cd concentrations in surface water were higher in summer, As and Zn were higher in spring, and Pb and Cu were higher in autumn and winter. Spatially, the concentrations of Cr, As, Cu, Zn, and Pb showed higher concentrations in the southern outlet of the reservoir, the northwestern Longxi River inlet, and the central part of the reservoir, whereas Cd was higher in the northern stagnant area. The overall levels of heavy metals in the water body of Changshou Lake were low, with Cr and Cu slightly polluted, while other heavy metals were identified as having an insignificant pollution level. Drinking water was the primary exposure pathway to carcinogenic and non-carcinogenic heavy metals in surface water bodies. The health risk values of Cr and As in water bodies were high, ranging from 6.2×10-10 to 3.0×10-4 and 5.1×10-8 to 3.9×10-5, respectively. The corresponding contribution rates for children and adults to the total health risk were high, with Cr accounting for 87.18% and 87.20%, respectively, while As accounted for 12.73% and 12.71%, respectively. Therefore, it is crucial to prioritize environmental risks associated with Cr and Cu, as well as the health risks associated with Cr and As in Changshou Lake These findings provide a scientific foundation for water pollution control and environmental quality improvement in Changshou Lake, and rational development and utilization of water resources.
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Água Potável , Metais Pesados , Poluentes Químicos da Água , Cádmio , China , Monitoramento Ambiental , Sedimentos Geológicos , Lagos/análise , Chumbo , Metais Pesados/análise , Medição de Risco , Poluentes Químicos da Água/análise , Humanos , Criança , AdultoRESUMO
OBJECTIVE: To analyze the expression of MCP-1 and CCR2 in newly diagnosed diffuse large B-cell lymphoma (DLBCL), and to evaluate their correlation with clinicopathological features and prognosis. METHODS: A total of 141 patients with DLBCL diagnosed and treated in the Department of Hematology, the First Affiliated Hospital of Bengbu Medical College from January 2017 to May 2022 were retrospectively collected. The clinical characteristics, pathological data and prognostic factors of the patients were collected. Immunohistochemical staining was used to detect the expression of MCP-1 and CCR2 in the tissues of newly treated DLBCL patients, and to analyze the relationship between MCP-1 and clinical characteristics, prognosis and survival of patients. RESULTS: The expression of MCP-1 and CCR2 were correlated with Ann Arbor stage, IPI score, lactate dehydrogenase (LDH), Ki-67 index and therapeutic effect. There were no significant correlation between the expression of MCP-1 or CCR2 and other clinical histopathological parameters such as gender, age, ß2-microglobulin, BCL-2, BCL-6, Hans classification, initial location, B symptoms, bone marrow involvement. There was a statistical difference in OS and PFS between the MCP-1 or CCR2 positive group and the negative group, which was associated to poor prognosis.Univariate Cox regression analysis showed that ß2-microglobulin, Ki-67 index, IPI score, MCP-1, CCR2 expression levels and disease remission affected the PFS and OS of DLBCL patients (P < 0.05). Gender, age, LDH, BCL-2, BCL-6, Hans classification, primary tumor site, B symptoms, bone marrow involvement, Ann Arbor stage had no effect on PFS and OS (P >0.05). Multivariate analysis showed that ß2-microglobulin, Ki-67 index, IPI score, MCP-1, CCR2 expression levels and disease remission were independent influencing factors of patients (P < 0.05). CONCLUSION: The expression rate of MCP-1 or CCR2 in newly treated DLBCL is high, and it is correlated with the clinical features of poor prognosis such as stage and LDH of DLBCL patients, which is a poor prognostic factor affecting PFS and OS.
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Relevância Clínica , Linfoma Difuso de Grandes Células B , Humanos , Antígeno Ki-67 , L-Lactato Desidrogenase , Linfoma Difuso de Grandes Células B/patologia , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2 , Receptores CCR2 , Estudos RetrospectivosRESUMO
Although the gut microbial metabolites exhibit potential effects on coronary heart disease (CHD), the underlying mechanism remains unclear. In this study, the active gut microbial metabolites acting on CHD and their potential mechanisms of action were explored through a network pharmacological approach. We collected a total of 208 metabolites from the gutMgene database and 726 overlapping targets from the similarity ensemble approach (SEA) and SwissTargetPrediction (STP) database, and ultimately identified 610 targets relevant to CHD. In conjunction with the gutMGene database, we identified 12 key targets. The targets of exogenous substances were removed, and 10 core targets involved in CHD were eventually retained. The microbiota-metabolites-targets-signalling pathways network analysis revealed that C-type lectin receptor signalling pathway, Lachnospiraceae, Escherichia, mitogen-activated protein kinase 1, prostaglandin-endoperoxidase synthase 2, phenylacetylglutamine and alcoholic acid are notable components of CHD and play important roles in the development of CHD. The results of molecular docking experiments demonstrated that AKT1-glycocholic acid and PTGS2-phenylacetylglutamine complexes may act on C-type lectin receptor signalling pathways. In this study, the key substances and potential mechanisms of gut microbial metabolites were analysed via network pharmacological methods, and a scientific basis and comprehensive idea were provided for the effects of gut microbial metabolites on CHD.
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Doença das Coronárias , Microbioma Gastrointestinal , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Ciclo-Oxigenase 2 , Lectinas Tipo CRESUMO
Pulmonary surfactant is a lipoprotein complex lining the alveolar surface to decrease the surface tension and facilitate inspiration. Surfactant deficiency is often seen in premature infants and in children and adults with respiratory distress syndrome. Mechanical stretch of alveolar type 2 epithelial (AT2) cells during lung expansion is the primary physiological factor that stimulates surfactant secretion; however, it is unclear whether there is a mechanosensor dedicated to this process. Here, we show that loss of the mechanosensitive channels TMEM63A and TMEM63B (TMEM63A/B) resulted in atelectasis and respiratory failure in mice due to a deficit of surfactant secretion. TMEM63A/B were predominantly localized at the limiting membrane of the lamellar body (LB), a lysosome-related organelle that stores pulmonary surfactant and ATP in AT2 cells. Activation of TMEM63A/B channels during cell stretch facilitated the release of surfactant and ATP from LBs fused with the plasma membrane. The released ATP evoked Ca2+ signaling in AT2 cells and potentiated exocytic fusion of more LBs. Our study uncovered a vital physiological function of TMEM63 mechanosensitive channels in preparing the lungs for the first breath at birth and maintaining respiration throughout life.
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Líquidos Corporais , Surfactantes Pulmonares , Adulto , Animais , Criança , Humanos , Lactente , Camundongos , Trifosfato de Adenosina , Pulmão , TensoativosRESUMO
Objective: To identify the representative attributes of the five elements of a person with a qualitative methodology and provide the basis for the clinical diagnosis and treatment of "people with the five elements in traditional Chinese medicine (TCM)." Methods: Data collected from the literature review, two sessions of brainstorming of experts with related experience in "people with the five elements in TCM" from October 2020 to December 2020, and six rounds of in-depth interviews with 30 participants who had various attributes of the five elements from March 2021 to October 2021 were analyzed. Triangulation was used in this study, and theming and synthesizing were used to analyze the data. Results: A total of 31 experts and 30 interviewees participated in this study. The median age of the experts and interviewees were 48.0 and 38.5 years, respectively; 51.66% and 54.8% of experts and interviewees, respectively, were men. The descriptors of facial diagrams of "people with the five elements in TCM" were complexion, shape, distribution state of facial bones, convergence trend of facial muscles, and facial expression. A theoretical model of "people with the five elements in TCM" was shaped based on these findings. Conclusion: The study suggests a possibility for bridging the gap between personality and bodily state, identifying an avenue for personality research from the perspective of TCM.
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Medicina Tradicional Chinesa , Técnicas Projetivas , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa/métodos , Adulto , Pessoa de Meia-Idade , DiagnósticoRESUMO
Most hematological tumors have high-grade malignancy and low cure rate, requiring new molecular markers for detection and evaluation. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed-loop structures, which participate in gene transcription and translation by binding to microRNAs and proteins. In recent years, with the deepening research on circRNAs, circRNAs have been found to play an important role in hematological malignancies. In this review, the latest research progress on the function and molecular mechanism of circRNAs in hematological malignancies was systematically summarized, and it was found that circRNAs may be potential new biomarkers and therapeutic targets in hematological malignancies.
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Neoplasias Hematológicas , MicroRNAs , Neoplasias , Humanos , RNA Circular , MicroRNAs/genética , Neoplasias Hematológicas/genética , BiomarcadoresRESUMO
BACKGROUND AND PURPOSE: Physical rehabilitation plays an important role in the recovery of motor function after a stroke. This study aimed to evaluate the effects of Tai Chi Yunshou (TCY), a form of physical therapy, on upper-limb function and balance in stroke survivors. METHODS: MEDLINE, Embase, CENTRAL and five Chinese databases were retrieved from inception to July 1, 2020 (updated on March 31, 2022). Randomized controlled trials of TCY versus no-treatment for stroke were included. The RoB-2 was used to evaluate the quality of included studies. Upper-limb motor impairment, balance, and activities of daily living (ADLs) were measured by Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE), Berg Balance Scale (BBS), and Barthel Index (BI), respectively. Data synthesis was performed using RevMan (v5.3), and expressed as mean difference (MD) with 95% confidence intervals (CI). RESULTS: Seven studies with 529 participants were included. Compared with no-treatment, TCY improved FMA-UE (MD = 7.31, 95% CI: 5.86-8.77, minimal clinically important difference [MCID]: 9-10), BBS (MD = 4.68, 95% CI: 0.28-9.07, MCID: 4), and BI (MD = 4.12, 95% CI: 3.28-4.96, MCID: 1.85) in stroke survivors. CONCLUSION: TCY may benefit balance and ADLs in rehabilitation after a stroke, but it may not improve upper-limb function clinically.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Tai Chi Chuan , Humanos , Atividades Cotidianas , Acidente Vascular Cerebral/terapia , Extremidade Superior , SobreviventesRESUMO
Replacement of first-generation or second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with third-generation EGFR-TKIs remains the current standard of care for T790M mutations in patients with non-small cell lung cancer. Osimertinib is one of the first third-generation EGFR-TKIs to be approved and is also the most widely studied in clinical research. There has been widespread concern about the adverse effects of osimertinib such as cardiotoxicity and interstitial lung disease, but few articles have reported severe thrombocytopenia after osimertinib treatment. This article reports a 64-year-old woman with non-small cell lung cancer initially diagnosed with cT2aN1M1a, EGFR p.L858R, who developed disease progression and T790M after 32 months of first-line treatment with gefitinib (250 mg/day) before switching to second-line treatment with osimertinib (80 mg/day). Severe thrombocytopenia and active bleeding occurred after treatment with osimertinib, which improved with recombinant human thrombopoietin and platelet transfusion. Treatment was replaced with aumolertinib (110 mg/day). After platelet stabilization with aumolertinib treatment in combination with chest radiotherapy, this patient had progression-free survival for 9 months and overall survival for over 45 months. In conclusion, from our experience, aumolertinib has good efficacy and mild adverse effects, and is a good choice for non-small cell lung cancer patients with T790M, especially for patients at high risk of thrombocytopenia.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Trombocitopenia , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptores ErbB/genética , Inibidores de Proteínas Quinases/farmacologia , Mutação , Compostos de Anilina/uso terapêuticoRESUMO
The changes in gut microbiota have been implicated in colorectal cancer (CRC). The interplays between the host and gut microbiota remain largely unclear, and few studies have investigated these interplays using integrative multi-omics data. In this study, large-scale multi-comic datasets, including microbiome, metabolome, bulk transcriptomics and single cell RNA sequencing of CRC patients, were analyzed individually and integrated through advanced bioinformatics methods. We further examined the clinical relevance of these findings in the mice recolonized with microbiota from human. We found that CRC patients had distinct microbiota compositions compared to healthy controls. A machine-learning model was developed with 28 biomarkers for detection of CRC, which had high accuracy and clinical applicability. We identified multiple significant correlations between genera and well-characterized genes, suggesting the potential role of gut microbiota in tumor immunity. Further analysis showed that specific metabolites worked as profound communicators between these genera and tumor immunity. Integrating microbiota and metabolome perspectives, we cataloged gut taxonomic and metabolomic features that represented the key multi-omics signature of CRC. Furthermore, gut microbiota transplanted from CRC patients compromised the response of CRC to immunotherapy. These phenotypes were strongly associated with the alterations in gut microbiota, immune cell infiltration as well as multiple metabolic pathways. The comprehensive interplays across multi-comic data of CRC might explain how gut microbiota influenced tumor immunity. Hence, we proposed that modifying the CRC microbiota using healthy donors might serve as a promising strategy to improve response to immunotherapy.
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Neoplasias Colorretais , Microbioma Gastrointestinal , Microbiota , Humanos , Camundongos , Animais , Microbioma Gastrointestinal/genética , Neoplasias Colorretais/metabolismo , Multiômica , Fezes , Microbiota/genéticaRESUMO
OBJECTIVE: To explore the expression of CD28 in multiple myeloma and its correlation with tumor burden and clinical prognosis. METHODS: Flow cytometry was adopted to analyze bone marrow specimens of 91 newly diagnosed patients with multiple myeloma. According to CD28 expression, the patients were divided into CD28+ group and CD28- group, and the differences between the two groups in clinical features, genetic abnormalities, and treatment response were compared. Staging was carried out in accordance with the International Staging System (ISS). RESULTS: Among 91 newly diagnosed patients, there were 31 cases in CD28+ group and 60 cases in CD28- group. The proportion of ISS-â ¢ patients in the CD28+ group was 70.97%, which was higher than 50.00% in the CD28- group (P<0.05). The median of bone marrow plasma cells in the CD28+ group was 41.78(2.00-77.00), which was higher than 26.92(2.00-92.00) in the CD28- group (P<0.05). ß2-microglobulin level in the CD28+ group was 6.53(2.11-36.50) mg/L, which was higher than 5.76(2.00-31.34) mg/L in the CD28- group (P<0.05). The positive rate of poor karyotype in the CD28+ group was 70.00% (21/30), which was higher than 45.00% (27/60) in the CD28- group (P=0.025). After 4 cycles of chemotherapy, the total effective rate of CD28- group was 86.27%, which was higher than 60.00% of CD28+ group (P<0.05). After a median follow-up of 10 months, the progression-free survival (PFS) time of CD28+ group was 10.7 months, which was lower than 14 months of CD28- group (P<0.05). Univariate analysis showed that age ≥ 65 years old, hemoglobin < 60 g/L, ISS-III, CD28+ expression and ≥ 2 genetic abnormalities were not risk factors for PFS, while further multivariate analysis showed that induction effect < partial response (PR) and CD28+ expression and were independent risk factors for PFS. CONCLUSION: CD28+ is associated with clinical characteristics and prognosis of newly diagnosed multiple myeloma patients, and can be used as a reference index to evaluate the prognosis.