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Cells keep their energy balance and avoid oxidative stress by regulating mitochondrial movement, distribution, and clearance. We report here that two Parkinson's disease proteins, the Ser/Thr kinase PINK1 and ubiquitin ligase Parkin, participate in this regulation by arresting mitochondrial movement. PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. Removal of Miro from the mitochondrion also detaches kinesin from its surface. By preventing mitochondrial movement, the PINK1/Parkin pathway may quarantine damaged mitochondria prior to their clearance. PINK1 has been shown to act upstream of Parkin, but the mechanism corresponding to this relationship has not been known. We propose that PINK1 phosphorylation of substrates triggers the subsequent action of Parkin and the proteasome.
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Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Animais , Proteínas de Drosophila/química , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Humanos , Camundongos , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/química , Dados de Sequência Molecular , Doença de Parkinson/metabolismo , Fosforilação , Ratos , Proteínas rho de Ligação ao GTP/químicaRESUMO
SignificanceOur work focuses on the critical longstanding question of the nontranscriptional role of p53 in tumor suppression. We demonstrate here that poly(ADP-ribose) polymerase (PARP)-dependent modification of p53 enables rapid recruitment of p53 to damage sites, where it in turn directs early repair pathway selection. Specifically, p53-mediated recruitment of 53BP1 at early time points promotes nonhomologous end joining over the more error-prone microhomology end-joining. Similarly, p53 directs nucleotide excision repair by mediating DDB1 recruitment. This property of p53 also correlates with tumor suppression in vivo. Our study provides mechanistic insight into how certain transcriptionally deficient p53 mutants may retain tumor-suppressive functions through regulating the DNA damage response.
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Dano ao DNA , Reparo do DNA por Junção de Extremidades , Proteína Supressora de Tumor p53/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proteínas de Ligação a DNA , Humanos , Mutação , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Domínios Proteicos , Proteína Supressora de Tumor p53/genética , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/genéticaRESUMO
Single-site photocatalysts (SSPCs) are well-established as potent platforms for designing innovative materials to accomplish direct solar-to-fuel conversion. Compared to classical inorganic porous materials, such as zeolites and silica, covalent organic frameworks (COFs)âan emerging class of porous polymers that combine high surface areas, structural diversity, and chemical stabilityâare attractive candidates for SSPCs due to their molecular-level precision and intrinsic light harvesting ability, both amenable to structural engineering. In this Perspective, we summarize the design concepts and state-of-the-art strategies for the construction of COF SSPCs, and we review the development of COF SSPCs and their applications in solar-to-fuel conversion from their inception. Underlying pitfalls concerning photocatalytic characterization are discussed, and perspectives for the future development of this burgeoning field are given.
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OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.
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Neoplasias Colorretais , Trombose , Tromboembolia Venosa , Humanos , Anticoagulantes/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Hemorragia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controleRESUMO
Hypophosphatasia (HPP) is a rare inborn error of metabolism that presents variably in both age of onset and severity. HPP is caused by pathogenic variants in the ALPL gene, resulting in low activity of tissue nonspecific alkaline phosphatase (TNSALP). Patients with HPP tend have a similar pattern of elevation of natural substrates that can be used to aid in diagnosis. No formal diagnostic guidelines currently exist for the diagnosis of this condition in children, adolescents, or adults. The International HPP Working Group is a comprised of a multidisciplinary team of experts from Europe and North America who have expertise in the diagnosis and management of patients with HPP. This group reviewed 93 papers through a Medline, Medline In-Process, and Embase search for the terms "HPP" and "hypophosphatasia" between 2005 and 2020 and that explicitly address either the diagnosis of HPP in children, clinical manifestations of HPP in children, or both. Two reviewers independently evaluated each full-text publication for eligibility and studies were included if they were narrative reviews or case series/reports that concerned diagnosis of pediatric HPP or included clinical aspects of patients diagnosed with HPP. This review focused on 15 initial clinical manifestations that were selected by a group of clinical experts.The highest agreement in included literature was for pathogenic or likely pathogenic ALPL variant, elevation of natural substrates, and early loss of primary teeth. The highest prevalence was similar, including these same three parameters and including decreased bone mineral density. Additional parameters had less agreement and were less prevalent. These were organized into three major and six minor criteria, with diagnosis of HPP being made when two major or one major and two minor criteria are present.
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Hipofosfatasia , Adulto , Criança , Humanos , Adolescente , Hipofosfatasia/diagnóstico , Hipofosfatasia/genética , Fosfatase Alcalina/genética , Europa (Continente) , Prevalência , MutaçãoRESUMO
Hypophosphatasia (HPP) is an inborn error of metabolism caused by reduced or absent activity of the tissue non-specific alkaline phosphatase (TNSALP) enzyme, resulting from pathogenic variants in the ALPL gene. Clinical presentation of HPP is highly variable, including lethal and severe forms in neonates and infants, a benign perinatal form, mild forms manifesting in adulthood, and odonto-HPP. Diagnosis of HPP remains a challenge in adults, as signs and symptoms may be mild and non-specific. Disease presentation varies widely; there are no universal signs or symptoms, and the disease often remains underdiagnosed or misdiagnosed, particularly by clinicians who are not familiar with this rare disorder. The absence of diagnosis or a delayed diagnosis may prevent optimal management for patients with this condition. Formal guidelines for the diagnosis of adults with HPP do not exist, complicating efforts for consistent diagnosis. To address this issue, the HPP International Working Group selected 119 papers that explicitly address the diagnosis of HPP in adults through a Medline, Medline In-Process, and Embase search for the terms "hypophosphatasia" and "HPP," and evaluated the pooled prevalence of 17 diagnostic characteristics, initially selected by a group of HPP clinical experts, in eligible studies and in patients included in these studies. Six diagnostic findings showed a pooled prevalence value over 50% and were considered for inclusion as major diagnostic criteria. Based on these results and according to discussion and consideration among members of the Working Group, we finally defined four major diagnostic criteria and five minor diagnostic criteria for HPP in adults. Authors suggested the integrated use of the identified major and minor diagnostic criteria, which either includes two major criteria, or one major criterion and two minor criteria, for the diagnosis of HPP in adults.
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Hipofosfatasia , Lactente , Adulto , Recém-Nascido , Humanos , Hipofosfatasia/diagnóstico , Hipofosfatasia/epidemiologia , Hipofosfatasia/genética , Fosfatase Alcalina/genética , Mutação , PrevalênciaRESUMO
BACKGROUND: This manuscript provides a summary of the current evidence to support the criteria for diagnosing a child or adult with hypophosphatasia (HPP). The diagnosis of HPP is made on the basis of integrating clinical features, laboratory profile, radiographic features of the condition, and DNA analysis identifying the presence of a pathogenic variant of the tissue nonspecific alkaline phosphatase gene (ALPL). Often, the diagnosis of HPP is significantly delayed in both adults and children, and updated diagnostic criteria are required to keep pace with our evolving understanding regarding the relationship between ALPL genotype and associated HPP clinical features. METHODS: An International Working Group (IWG) on HPP was formed, comprised of a multidisciplinary team of experts from Europe and North America with expertise in the diagnosis and management of patients with HPP. Methodologists (Romina Brignardello-Petersen and Gordon Guyatt) and their team supported the IWG and conducted systematic reviews following the GRADE methodology, and this provided the basis for the recommendations. RESULTS: The IWG completed systematic reviews of the literature, including case reports and expert opinion papers describing the phenotype of patients with HPP. The published data are largely retrospective and include a relatively small number of patients with this rare condition. It is anticipated that further knowledge will lead to improvement in the quality of genotype-phenotype reporting in this condition. CONCLUSION: Following consensus meetings, agreement was reached regarding the major and minor criteria that can assist in establishing a clinical diagnosis of HPP in adults and children.
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Hipofosfatasia , Adulto , Criança , Humanos , Hipofosfatasia/diagnóstico , Hipofosfatasia/genética , Mutação , Estudos Retrospectivos , Fosfatase Alcalina/genética , Genótipo , FenótipoRESUMO
BACKGROUND: Subjective cognitive decline (SCD) is an early stage of dementia linked to Alzheimer's disease pathology. White matter changes were found in SCD using diffusion tensor imaging, but there are known limitations in voxel-wise tensor-based methods. Fixel-based analysis (FBA) can help understand changes in white matter fibers and how they relate to neurodegenerative proteins and multidomain behavior data in individuals with SCD. METHODS: Healthy adults with normal cognition were recruited in the Northeastern Taiwan Community Medicine Research Cohort in 2018-2022 and divided into SCD and normal control (NC). Participants underwent evaluations to assess cognitive abilities, mental states, physical activity levels, and susceptibility to fatigue. Neurodegenerative proteins were measured using an immunomagnetic reduction technique. Multi-shell diffusion MRI data were collected and analyzed using whole-brain FBA, comparing results between groups and correlating them with multidomain assessments. RESULTS: The final enrollment included 33 SCD and 46 NC participants, with no significant differences in age, sex, or education between the groups. SCD had a greater fiber-bundle cross-section than NC (pFWE < 0.05) at bilateral frontal superior longitudinal fasciculus II (SLFII). These white matter changes correlate negatively with plasma Aß42 level (r = -0.38, p = 0.01) and positively with the AD8 score for subjective cognitive complaints (r = 0.42, p = 0.004) and the Hamilton Anxiety Rating Scale score for the degree of anxiety (Ham-A, r = 0.35, p = 0.019). The dimensional analysis of FBA metrics and blood biomarkers found positive correlations of plasma neurofilament light chain with fiber density at the splenium of corpus callosum (pFWE < 0.05) and with fiber-bundle cross-section at the right thalamus (pFWE < 0.05). Further examination of how SCD grouping interacts between the correlations of FBA metrics and multidomain assessments showed interactions between the fiber density at the corpus callosum with letter-number sequencing cognitive score (pFWE < 0.01) and with fatigue to leisure activities (pFWE < 0.05). CONCLUSION: Based on FBA, our investigation suggests white matter structural alterations in SCD. The enlargement of SLFII's fiber cross-section is linked to plasma Aß42 and neuropsychiatric symptoms, which suggests potential early axonal dystrophy associated with Alzheimer's pathology in SCD. The splenium of the corpus callosum is also a critical region of axonal degeneration and cognitive alteration for SCD.
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Biomarcadores , Disfunção Cognitiva , Substância Branca , Humanos , Masculino , Feminino , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Biomarcadores/sangue , Pessoa de Meia-Idade , Idoso , Imagem de Tensor de Difusão/métodos , Peptídeos beta-Amiloides/sangue , Adulto , Estudos de Coortes , Autoavaliação DiagnósticaRESUMO
OBJECTIVE: To explore the neuroimage change in Parkinson's disease (PD) patients with cognitive impairments, this study investigated the correlation between plasma biomarkers and morphological brain changes in patients with normal cognition and mild cognitive impairment. The objective was to identify the potential target deposition regions of the plasma biomarkers and to search for the relevant early neuroimaging biomarkers on the basis of different cognitive domains. METHODS: Structural brain MRI and diffusion weighted images were analyzed from 49 eligible PD participants (male/female: 27/22; mean age: 73.4 ± 8.5 years) from a retrospective analysis. Plasma levels of α-synuclein, amyloid beta peptide, and total tau were collected. A comprehensive neuropsychological assessment of the general and specific cognitive domains was performed. Difference between PD patients with normal cognition and impairment was examined. Regression analysis was performed to evaluate the correlation between image-derived index and plasma biomarkers or neuropsychological assessments. RESULTS: Significant correlation was found between plasma Aß-42 level and fractional anisotropy of the middle occipital, angular, and middle temporal gyri of the left brain, as well as plasma T-tau level and the surface area of the isthmus or the average thickness of the posterior part of right cingulate gyrus. Visuospatial and executive function is positively correlated with axial diffusivity in bilateral cingulate gyri. CONCLUSION: In nondemented PD patients, the target regions for plasma deposition might be located in the cingulate, middle occipital, angular, and middle temporal gyri. Changes from multiple brain regions can be correlated to the performance of different cognitive domains. CLINICAL RELEVANCE STATEMENT: Cognitive impairment in Parkinson's disease is primarily linked to biomarkers associated with Alzheimer's disease rather than those related to Parkinson's disease and resembles the frontal variant of Alzheimer's disease, which may guide management strategies for cognitive impairment in Parkinson's disease. KEY POINTS: ⢠Fractional anisotropy, surface area, and thickness in the cingulate, middle occipital, angular, and middle temporal gyri can be significantly correlated with plasma Aß-42 and T-tau level. ⢠Axial diffusivity in the cingulate gyri was correlated with visuospatial and executive function. ⢠The pattern of cognitive impairment in Parkinson's disease can be similar to the frontal variant than typical Alzheimer's disease.
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Doença de Alzheimer , Disfunção Cognitiva , Doença de Parkinson , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides , Estudos Retrospectivos , Disfunção Cognitiva/complicações , Disfunção Cognitiva/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Testes Neuropsicológicos , BiomarcadoresRESUMO
OBJECTIVES: Health-related quality-of-life (HRQoL) instruments for cardiovascular diseases (CVD) have been commonly used to measure important patient-reported outcomes (PROs) in clinical trials and practices. This study aimed at systematically identifying and assessing the content validity of CVD-specific HRQoL instruments in clinical studies. METHODS: The research team searched Cumulative Index to Nursing and Allied Health Literature, Embase, and PubMed from inception to January 20, 2022. The research team included studies that reported the development and content validity for CVD-specific instruments. Two reviewers independently assessed the methodological quality using the Consensus-based Standards for the Selection of Health Measurement Instruments methods on evaluating content validity of PROs. Content analysis was used to categorize the items included in the instruments. RESULTS: The research team found 69 studies reporting the content validity of 40 instruments specifically developed for CVD. Fourteen (35.0%) were rated "sufficient" with very low to moderate quality of evidence. For PRO development, all instruments were rated "doubtful" or "inadequate." Twenty-eight (70.0%) instruments cover the core concepts of HRQoL. CONCLUSIONS: The quality of development and content validity vary among existing CVD-specific instruments. The evidence on the content validity should be considered when choosing a HRQoL instrument in CVD clinical studies and health economic evaluations.
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Doenças Cardiovasculares , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários , PsicometriaRESUMO
A novel monopartite dsRNA virus, tentatively named "sponge gourd amalgavirus 1" (SGAV1), was discovered by high-throughput sequencing in sponge gourd (Luffa cylindrica) displaying mosaic symptoms in Jiashan County, Zhejiang Province, China. The genome of SGAV1 is 3,447 nucleotides in length and contains partially overlapping open reading frames (ORFs) encoding a putative replication factory matrix-like protein and a fusion protein, respectively. The fusion protein of SGAV1 shares 57.07% identity with the homologous protein of salvia miltiorrhiza amalgavirus 1 (accession no. DAZ91057.1). Phylogenetic analysis based on the RNA-dependent RNA polymerase (RdRp) protein suggests that SGAV1 belongs to the genus Amalgavirus of the family Amalgaviridae. Moreover, analysis of SGAV1-derived small interfering RNAs indicated that SGAV1 was actively replicating in the host plant. Semi-quantitative RT-PCR showed higher levels of SGAV1 expression in leaves than in flowers and fruits. This is the first report of a novel amalgavirus found in sponge gourd in China.
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Genoma Viral , Luffa , Fases de Leitura Aberta , Filogenia , Genoma Viral/genética , Luffa/virologia , Animais , China , Vírus de RNA de Cadeia Dupla/genética , Vírus de RNA de Cadeia Dupla/classificação , Vírus de RNA de Cadeia Dupla/isolamento & purificação , Sequenciamento Completo do Genoma , Proteínas Virais/genética , RNA Viral/genética , RNA Polimerase Dependente de RNA/genéticaRESUMO
OBJECTIVE: To compare the outcomes associated with the use of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults. METHODS: We searched eight electronic databases from database inception to July 11, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the treatment of chronic constipation. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of the evidence was assessed using the Confidence in Network Meta-Analysis framework. The analysis was conducted using R version 4.3.0. RESULTS: Out of the 37 RCTs, a total of 21 different types of interventions were reported, involving 3,903 patients. This NMA demonstrated that both prebiotics and synbiotics resulted in an increase in frequency of stool movements per week. Compared to placebo, lactulose (Mean difference [MD] = 3.39, 95% Confdence interval [CI] [1.13, 5.65], moderate certainty), mix2 (consisting of Lactulose and Bacillus coagulans) (MD = 3.63, 95% CI [1.37, 5.89], moderate certainty), mix6 (consisting of Lactulose and Bifidobacterium coagulans) (MD = 4.30, 95% CI [1.04, 7.54], low certainty), and mix7 (consisting of Lactulose, Bifidobacterium subtilis, and Enterococcus faecium) (MD = 4.58, 95% CI [1.35, 7.78], moderate certainty) exhibited a significant effect. Notably, mix7 demonstrated the highest probability of being the most effective intervention (94.8%). Furthermore, when compared to L. plantarum, four probiotics and two synbiotics showed significant advantages in the Patient Assessment of Constipation Symptoms (PAC-SYM) score. L. reuteri (MD = -13.74, 95% CI [-22.20, -4.66], very low certainty) exhibited a significant effect in improving the Patient Assessment of Constipation Quality of Life (PAC-QoL) score. In terms of safety, there were no statistically significant differences between the intervention and control groups in all adverse event analyses. CONCLUSIONS: Moderate to very low evidence supports the use of lactulose and synbiotics to increase the number of weekly stool movements in patients, particularly highlighting the significant impact of synbiotics in increasing the number of weekly stool movements in patients with constipation. The use of L. paracasei showed improvements in PAC-SYM scores, while L. reuteri demonstrated enhancements in PAC-QoL scores.
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Constipação Intestinal , Metanálise em Rede , Prebióticos , Probióticos , Simbióticos , Constipação Intestinal/terapia , Humanos , Prebióticos/administração & dosagem , Simbióticos/administração & dosagem , Probióticos/administração & dosagem , Probióticos/uso terapêutico , Doença Crônica , Adulto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Rice cultivation in Jilin Province, China, encounters challenges associated with straw management and nitrogen fertilizer usage. This study explores the effects of dynamic nitrogen fertilizer application combined with straw incorporation on soil properties, rice yield, and quality. High-quality Japonica rice varieties, "Jihong 9â³ and "Jinongda 853," were cultivated in a 3-year trial across different regions. Results showed that dynamic nitrogen fertilizer application under straw incorporation significantly improved soil properties, leading to increased yields. Over the years, the average yield in straw retuning (SR) was 10,566 kg/ha, surpassing conventional practices (CK) at 9939 kg/ha. SR exhibited higher effective tiller rates, spike numbers, and grain numbers per spike, contributing to enhanced yields. Quality analysis revealed that SR rice exhibited lower protein content, resulting in reduced chalkiness and improved taste quality, making it a more desirable option. These findings highlight the effectiveness of sustainable agricultural practices in optimizing rice production in Jilin Province.
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Oryza , Nitrogênio/análise , Fertilizantes , Solo , Agricultura/métodos , ChinaRESUMO
INTRODUCTION: The use of intracytoplasmic sperm injection (ICSI) has dramatically increased in patients with non-male factor infertility during the last decades. However, whether ICSI provides a significant benefit over in vitro fertilization (IVF) in these patients is still controversial. In this study, we aimed to investigate the efficacy of ICSI on reproductive outcomes with non-male factor infertility and to provide updated evidence for clinical practice. MATERIAL AND METHODS: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2023. Randomized controlled trials (RCTs) comparing the efficacy between ICSI and IVF in patients with non-male factor infertility were included. The main outcomes were the live birth rate (LBR), fertilization rate (FR), and total fertilization failure (TFF). The pooled estimates were calculated using the random-effects models as relative risk (RR) with 95% confidence intervals (CIs). This systematic review and meta-analysis was registered in PROSPERO (CRD42023427004). RESULTS: We included 18 RCTs with 3249 cycles and 30 994 oocytes. The results demonstrated that ICSI reduced the risk of TFF (RR = 0.26, 95% CI: 0.13-0.50, I2 = 58%) and increased FR per oocyte inseminated/injected (RR = 1.14, 95% CI: 1.08-1.20, I2 = 69%), but it did not improve LBR (RR = 1.11, 95% CI: 0.94-1.30, I2 = 0%) or other outcomes compared with IVF. However, the difference in fertilization failure reduction between ICSI and IVF may be explained by different randomization methods (randomization based on patients vs. sibling oocytes). When considering only studies with randomization based on patients, we found no evidence of the difference between the groups (RR = 0.72, 95% CI: 0.48-1.06, I2 = 0%). Furthermore, no differences were observed in subgroup analyses based on other factors, including female age, study period, and controlled ovarian stimulation protocols. CONCLUSIONS: Our findings suggest that ICSI leads to no difference in reproductive outcomes compared to IVF in patients with non-male factor infertility. Considering the cost and safety of ICSI, we have no evidence to support the routine use of ICSI in these populations. High-quality RCTs with large sample sizes will be needed to confirm our results and explore clinical and neonatal outcomes.
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Infertilidade , Injeções de Esperma Intracitoplásmicas , Feminino , Humanos , Recém-Nascido , Gravidez , Fertilização in vitro/métodos , Indução da Ovulação/métodos , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas/métodosRESUMO
QiXueShuFu Decoction (QXSFD) modified from the Bazhen Decoction which was originally from the classic Ming Dynasty is a traditional folk formula that boosts the body's immune system. However, its ambiguous chemical components limited its quality control evaluation. In this study, ultra-performance liquid chromatography (UPLC) fingerprint combined with multivariate analysis was used to evaluate the quality of 15 batches of QXSFD, and UPLC quadrupole-orbitrap mass spectrometry was used to further examine the chemical components in QXSFD, after which representative compounds from each disassembled prescription were selected for comparison. Fifteen batches of samples had 33 common peaks in which 11 differential components could be used as a reference for subsequent quality control. One hundred forty-three components were identified from QXSFD. Saponins were mainly derived from the monarch, terpenes from the minister, and polysaccharides and glycosides from the assistant. In addition, quantitative assay revealed that the content of ferulic acid, chlorogenic acid, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside and 3,6'-disinapoyl sucrose in the whole prescription were higher than the contents of each disassembled prescription. This is the first comprehensive quality report on the chemical components of QXSFD, which is important for pharmacodynamic material basis and quality control.
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Medicamentos de Ervas Chinesas , Saponinas , Medicamentos de Ervas Chinesas/análise , Cromatografia Líquida de Alta Pressão/métodos , Glicosídeos , Saponinas/análise , Espectrometria de Massa com Cromatografia LíquidaRESUMO
BACKGROUND: The clinical efficacy and safety of intravenous immunoglobulin (IVIg) treatment for COVID-19 remain controversial. This study aimed to map the current status and gaps of available evidence, and conduct a meta-analysis to further investigate the benefit of IVIg in COVID-19 patients. METHODS: Electronic databases were searched for systematic reviews/meta-analyses (SR/MAs), primary studies with control groups, reporting on the use of IVIg in patients with COVID-19. A random-effects meta-analysis with subgroup analyses regarding study design and patient disease severity was performed. Our outcomes of interest determined by the evidence mapping, were mortality, length of hospitalization (days), length of intensive care unit (ICU) stay (days), number of patients requiring mechanical ventilation, and adverse events. RESULTS: We included 34 studies (12 SR/MAs, 8 prospective and 14 retrospective studies). A total of 5571 hospitalized patients were involved in 22 primary studies. Random-effects meta-analyses of very low to moderate evidence showed that there was little or no difference between IVIg and standard care or placebo in reducing mortality (relative risk [RR] 0.91; 95% CI 0.78-1.06; risk difference [RD] 3.3% fewer), length of hospital (mean difference [MD] 0.37; 95% CI - 2.56, 3.31) and ICU (MD 0.36; 95% CI - 0.81, 1.53) stays, mechanical ventilation use (RR 0.92; 95% CI 0.68-1.24; RD 2.8% fewer), and adverse events (RR 0.98; 95% CI 0.84-1.14; RD 0.5% fewer) of patients with COVID-19. Sensitivity analysis using a fixed-effects model indicated that IVIg may reduce mortality (RR 0.76; 95% CI 0.60-0.97), and increase length of hospital stay (MD 0.68; 95% CI 0.09-1.28). CONCLUSION: Very low to moderate certainty of evidence indicated IVIg may not improve the clinical outcomes of hospitalized patients with COVID-19. Given the discrepancy between the random- and fixed-effects model results, further large-scale and well-designed RCTs are warranted.
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COVID-19 , Imunoglobulinas Intravenosas , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos , Revisões Sistemáticas como AssuntoRESUMO
The hydroxide exchange membrane fuel cell (HEMFC) is a promising energy conversion technology but is limited by the need for platinum group metal (PGM) electrocatalysts, especially for the hydrogen oxidation reaction (HOR). Here we report a Ni-based HOR catalyst that exhibits an electrochemical surface area-normalized exchange current density of 70 µA cm-2, the highest among PGM-free catalysts. The catalyst comprises Ni nanoparticles embedded in a nitrogen-doped carbon support. According to X-ray and ultraviolet photoelectron spectroscopy as well as H2 chemisorption data, the electronic interaction between the Ni nanoparticles and the support leads to balanced hydrogen and hydroxide binding energies, which are the likely origin of the catalyst's high activity. PGM-free HEMFCs employing this Ni-based HOR catalyst give a peak power density of 488 mW cm-2, up to 6.4 times higher than previous best-performing analogous HEMFCs. This work demonstrates the feasibility of efficient PGM-free HEMFCs.
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Níquel , Platina , Hidrogênio/química , Hidróxidos , Níquel/química , Oxirredução , Platina/químicaRESUMO
The superfamily Eriophyoidea includes >5000 named species of very small phytophagous mites. As for many groups of phytophagous invertebrates, factors responsible for diversification of eriophyoid mites are unclear. Here, we used an inferred phylogeny of 566 putative species of eriophyoid mites based on fragments of two mitochondrial genes and two nuclear genes to examine factors associated with their massive evolutionary diversification through time. Our dated phylogeny indicates a Carboniferous origin for gymnosperm-associated Eriophyoidea with subsequent diversification involving multiple host shifts to angiosperms-first to dicots, and then to monocots or shifts back to gymnosperms-beginning in the Cretaceous period when angiosperms diverged. Speciation rates increased more rapidly in the Eriophyidae + Diptilomiopidae (mostly infesting angiosperms) than in the Phytoptidae (mostly infesting gymnosperms). Phylogenetic signal, speciation rates, dispersal and vicariance results combined with inferred topologies show that hosts played a key role in the evolution of eriophyoid mites. Speciation constrained by hosts was probably the main driver behind eriophyoid mite diversification worldwide. We demonstrate monophyly of the Eriophyoidea, whereas all three families, most subfamilies, tribes, and most genera are not monophyletic. Our time-calibrated tree provides a framework for further evolutionary studies of eriophyoid mites and their interactions with host plants as well as taxonomic revisions above the species level.
Assuntos
Magnoliopsida , Ácaros , Humanos , Animais , Filogenia , Ácaros/genética , Magnoliopsida/genética , Genes Mitocondriais , Núcleo Celular/genéticaRESUMO
BACKGROUND: There are debates in acupuncture related systematic reviews and meta-analyses on whether searching Chinese databases to get more Chinese-language studies may increase the risk of bias and overestimate the effect size, and whether the treatment effects of acupuncture differ between Chinese and non-Chinese populations. METHODS: In this meta-epidemiological study, we searched the Cochrane library from its inception until December 2021, and identified systematic reviews and meta-analyses with acupuncture as one of the interventions. Paired reviewers independently screened the reviews and extracted the information. We repeated the meta-analysis of the selected outcomes to separately pool the results of Chinese- and non-Chinese-language acupuncture studies and presented the pooled estimates as odds ratios (OR) with 95% confidence interval (CI). We calculated the Ratio of ORs (ROR) by dividing the OR of the Chinese-language trials by the OR of the non-Chinese-language trials, and the ROR by dividing the OR of trials addressing Chinese population by the OR of trials addressing non-Chinese population. We explored whether the impact of a high risk of bias on the effect size differed between studies published in Chinese- and in non-Chinese-language, and whether the treatment effects of acupuncture differed between Chinese and non-Chinese population. RESULTS: We identified 84 Cochrane acupuncture reviews involving 33 Cochrane groups, of which 31 reviews (37%) searched Chinese databases. Searching versus not searching Chinese databases significantly increased the contribution of Chinese-language literature both to the total number of included trials (54% vs. 15%) and the sample size (40% vs. 15%). When compared with non-Chinese-language trials, Chinese-language trials were associated with a larger effect size (pooled ROR 0.51, 95% CI 0.29 to 0.91). We also observed a higher risk of bias in Chinese-language trials in blinding of participants and personnel (97% vs. 51%) and blinding of outcome assessment (93% vs. 47%). The higher risk of bias was associated with a larger effect estimate in both Chinese-language (allocation concealment: high/unclear risk vs. low risk, ROR 0.43, 95% CI 0.21 to 0.87) and non-Chinese-language studies (blinding of participants and personnel: high/unclear risk vs. low risk, ROR 0.41, 95% CI 0.23 to 0.74). However, we found no evidence that the higher risk of bias would increase the effect size of acupuncture in Chinese-language studies more often than in non-Chinese-language studies (the confidence intervals of all ROR in the high-risk group included 1, Table 3). We further found acupuncture appeared to be more effective in Chinese than in non-Chinese population (Table 4). CONCLUSIONS: The findings of this study suggest the higher risk of bias may lead to an overestimation of the treatment effects of acupuncture but would not increase the treatment effects in Chinese-language studies more often than in other language studies. The difference in treatment effects of acupuncture was probably associated with differences in population characteristics. TRIAL REGISTRATION: We registered our protocol on the Open Science Framework (OSF) ( https://doi.org/10.17605/OSF.IO/PZ6XR ).
Assuntos
Terapia por Acupuntura , Humanos , Terapia por Acupuntura/métodos , Viés , Idioma , Avaliação de Resultados em Cuidados de Saúde/métodos , Tamanho da Amostra , Revisões Sistemáticas como Assunto , Metanálise como AssuntoRESUMO
BACKGROUND: Wound infection after inguinal hernia surgery is not uncommon in the clinical setting. The common microbial aetiology of postoperative inguinal hernia wound infection is Gram-positive bacteria. Staphylococcus aureus is a common pathogen causing wound infection while Staphylococcus epidermidis and Pseudomonas are rare. Staphylococcus epidermidis as a cause of severe wound infection is rarely described in literature. We herein present a case of a 79-year-old man with a rare wound infection after bilateral inguinal herniorrhaphy caused by MRCNS (Methicillin Resistant Coagulase Negative Staphylococcus). CASE PRESENTATION: We present a case of wound infection accompanied by fever with a temperature of 38.8 °C after bilateral inguinal herniorrhaphy in a 79-year-old man. Bilateral inguinal wounds were marked by redness and swelling, with skin necrosis. In addition, an abscess of approximately 1.5 cm × 1.5 cm was seen on the left wrist. A small amount of gas under the skin in the wound area was observed after pelvic computed tomography (CT) scans. No bacteria were cultured from the inguinal wound discharge, while blood culture detected MRCNS, and Acinetobacter lwoffi was cultured from the pus in the left wrist. We chose appropriate antibiotics based on the results of the bacterial culture and the drug susceptibility results. Vacuum assisted closure (VAC) therapy was used after debridement. The patient was discharged after the wounds improved. He was followed up for ten months and showed no signs of complications. We are sharing our experience along with literature review. CONCLUSIONS: We are presenting a rare case of MRCNS wound infection following open inguinal hernia surgery. Although a rarity, clinicians performing inguinal hernia surgery must consider this entity in an infected wound and follow up the patient for complications of MRCNS.