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The pathogenesis of osteoarthritis (OA) involves a multifaceted interplay of inflammatory processes. The initiation of pyroptosis involves the secretion of pro-inflammatory cytokines and has been identified as a critical factor in regulating the development of OA. Upon initiation of pyroptosis, a multitude of inflammatory mediators are released and can be disseminated throughout the synovial fluid within the joint cavity, thereby facilitating intercellular communication across the entire joint. The main cellular components of joints include chondrocytes (CC), fibroblast-like synoviocytes (FLS) and macrophages (MC). Investigating their interplay can enhance our understanding of OA pathogenesis. Therefore, we comprehensively examine the mechanisms underlying pyroptosis and specifically investigate the intercellular interactions associated with pyroptosis among these three cell types, thereby elucidating their collective contribution to the progression of OA. We propose the concept of ' CC-FLS-MC pyroptosis-related crosstalk', describe the various pathways of pyroptotic interactions among these three cell types, and focus on recent advances in intervening pyroptosis in these three cell types for treating OA. We hope this will provide a possible direction for diversification of treatment for OA. The Translational potential of this article. The present study introduces the concept of 'MC-FLS-CC pyroptosis-related crosstalk' and provides an overview of the mechanisms underlying pyroptosis, as well as the pathways through which it affects MC, FLS, and CC. In addition, the role of regulation of these three types of cellular pyroptosis in OA has also been concerned. This review offers novel insights into the interplay between these cell types, with the aim of providing a promising avenue for diversified management of OA.
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Arthroscopic repair of Bankart injury is the first choice for the treatment of anterior shoulder instability. How to avoid recurring shoulder joint dislocation is a challenge, especially when combined with Hill-Sachs lesions. The arthroscopy technology allows for broader vision and less surgical trauma but is limited by a smaller operating space. At present, extensive descriptions about the surgical procedure of arthroscopic Bankart repair have been published. In this Technical Note, we describe the use of remplissage filling with Hill-Sachs lesion combined with Bankart repair to further improve the surgical accuracy and clinical efficacy. In particular, the application of single needle-assisted outside-in remplissage technique and Bankart repair is introduced in detail.
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OBJECTIVE: To compare the clinical outcomes of intensive glucose control and liberal glucose control for septic patients in intensive care unit. METHODS: The databases of PubMed, Cochrane Library, Embase and Web of Science were searched systematically from inception to November 27, 2023 to identify trials involving a randomized comparison between intensive and liberal glucose control for septic patients in intensive care unit. RESULTS: A total of 14 randomized controlled trials involving 6226 patients were finally included. There was no statistically significant difference observed between intensive glucose control and liberal glucose control in terms of all-cause mortality, the need for renal replacement, vasopressor-free and mechanical ventilation-free days, and length of hospital stay. However, it is noteworthy that intensive glucose control exhibited a statistically higher risk of severe hypoglycemia (RR 2.66; 95%CI 1.85 to 3.83), need for blood transfusion (RR 1.12; 95%CI 1.01 to 1.23), and statistically prolonged length of stay in the ICU (MD 1.67; 95%CI 0.22 to 3.12) compared to liberal glucose control. Nevertheless, sensitivity analysis revealed that the need for blood transfusion and length of stay in the intensive care unit were not robust. CONCLUSIONS: Both intensive and liberal glucose control had comparable effects on improving patient outcomes, but intensive glucose control carried a higher risk of severe hypoglycemia.
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Glicemia , Unidades de Terapia Intensiva , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse , Humanos , Glicemia/análise , Controle Glicêmico/métodos , Prognóstico , Hipoglicemia/prevenção & controle , Tempo de InternaçãoRESUMO
The anterior cruciate ligament (ACL) is the primary soft-tissue structure for anterior stabilization of the knee and is one of the most frequently injured structures. The incidence of ACL injuries in children and adolescents ranges from 92 to 151 per 100,000 person-years. The choice of surgical treatment for this population group is controversial, with a widespread concern that adult reconstruction techniques may damage the epiphyseal plate, compromise growth, or cause deformity. In this article, we describe a physeal-sparing, all-inside ACL reconstruction technique for skeletally immature patients. This technique is supported by retrograde drilling of the femoral tunnel and retrograde drilling of the tibial tunnel, both of which are able to avoid the epiphyseal growth line. Fixation of the quadrupled semitendinosus autograft and suture tape augmentation are achieved by soft-tissue buttons on the femur and tibia. The surgical details of this reproducible reconstruction technique are elaborated.
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Streptomyces has the largest repertoire of natural product biosynthetic gene clusters (BGCs), yet developing a universal engineering strategy for each Streptomyces species is challenging. Given that some Streptomyces species have larger BGC repertoires than others, we proposed that a set of genes co-evolved with BGCs to support biosynthetic proficiency must exist in those strains, and that their identification may provide universal strategies to improve the productivity of other strains. We show here that genes co-evolved with natural product BGCs in Streptomyces can be identified by phylogenomics analysis. Among the 597 genes that co-evolved with polyketide BGCs, 11 genes in the 'coenzyme' category have been examined, including a gene cluster encoding for the cofactor pyrroloquinoline quinone. When the pqq gene cluster was engineered into 11 Streptomyces strains, it enhanced production of 16,385 metabolites, including 36 known natural products with up to 40-fold improvement and several activated silent gene clusters. This study provides an innovative engineering strategy for improving polyketide production and finding previously unidentified BGCs.
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Produtos Biológicos , Família Multigênica , Streptomyces , Produtos Biológicos/metabolismo , Streptomyces/genética , Streptomyces/metabolismo , Policetídeos/metabolismo , Evolução Molecular , Vias Biossintéticas/genética , Filogenia , Engenharia Metabólica/métodosAssuntos
Fármacos Antiobesidade , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Obesidade , Redução de Peso , Adulto , Humanos , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/terapia , Redução de Peso/efeitos dos fármacos , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/efeitos adversos , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Estilo de Vida SaudávelRESUMO
To compared the arthroscopic capsular release (ACR) with manipulation under anaesthesia (MUA) for the surgical treatment of frozen shoulder (FS) based on postoperative outcomes and complications. PubMed, Cochrane Library, Embase, and Web of Science were searched on October 2, 2023 to retrieve eligible studies that compared ACR with MUA in terms of clinical outcomes (pain visual analogue scale, external rotation, forward flexion and adverse events) for patients with FS. Mean differences (MD) were calculated for continuous outcomes and odds ratios (OR) were calculated for dichotomous outcomes. Six papers, including 5 clinical studies (a total of 690 shoulders), were included in the final meta-analysis. The forward flexion was found to be larger in the ACR group at 3 months (MD, 2.73; 95%CI, 0.42-5.04; I2 = 44%; P = 0.02) and 6 months (MD, 2.36; 95%CI, 1.29-3.44; I2 = 0%; P < 0.0001). Except for this, ACR was comparable with MUA in terms of pain visual analogue scale at 3, 6 and 12 months (p = 0.25, p = 0.11, p = 0.28, respectively), external rotation at 3, 6 and 12 months (p = 0.15, p = 0.52, p = 0.23, respectively), and forward flexion at 12 months (p = 0.08). There were no differences in complication rates between the two groups (OR, 0.82; 95%CI, 0.47-1.44; I2 = 0%; P = 0.50). In comparison with MUA, ACR demonstrated better outcomes for forward flexion at 3 and 6 months, while there were no significant differences between ACR and MUA in terms of pain visual analogue scale, external rotation and adverse events.
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Currently, there are limited studies assessing ChatGPT ability to provide appropriate responses to medical questions. Our study aims to evaluate ChatGPT adequacy in responding to questions regarding osteoporotic fracture prevention and medical science. We created a list of 25 questions based on the guidelines and our clinical experience. Additionally, we included 11 medical science questions from the journal Science. Three patients, 3 non-medical professionals, 3 specialist doctor and 3 scientists were involved to evaluate the accuracy and appropriateness of responses by ChatGPT3.5 on October 2, 2023. To simulate a consultation, an inquirer (either a patient or non-medical professional) would send their questions to a consultant (specialist doctor or scientist) via a website. The consultant would forward the questions to ChatGPT for answers, which would then be evaluated for accuracy and appropriateness by the consultant before being sent back to the inquirer via the website for further review. The primary outcome is the appropriate, inappropriate, and unreliable rate of ChatGPT responses as evaluated separately by the inquirer and consultant groups. Compared to orthopedic clinicians, the patients' rating on the appropriateness of ChatGPT responses to the questions about osteoporotic fracture prevention was slightly higher, although the difference was not statistically significant (88% vs 80%, Pâ =â .70). For medical science questions, non-medical professionals and medical scientists rated similarly. In addition, the experts' ratings on the appropriateness of ChatGPT responses to osteoporotic fracture prevention and to medical science questions were comparable. On the other hand, the patients perceived that the appropriateness of ChatGPT responses to osteoporotic fracture prevention questions was slightly higher than that to medical science questions (88% vs 72·7%, Pâ =â .34). ChatGPT is capable of providing comparable and appropriate responses to medical science questions, as well as to fracture prevention related issues. Both the inquirers seeking advice and the consultants providing advice recognize ChatGPT expertise in these areas.
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Medicina , Ortopedia , Fraturas por Osteoporose , Médicos , Humanos , Encaminhamento e ConsultaRESUMO
BACKGROUND: Degenerative meniscal tear (DMT) is common in the elderly population. However, there has been controversy over the treatment of DMT regarding whether to adopt arthroscopic partial meniscectomy (APM) or exercise therapy (ET). In order to compare the long-term outcomes between the two treatment methods, we conducted a meta-analysis of randomized controlled trials (RCTs) with long-term follow-up. METHODS: PubMed, Cochrane Library, Embase, and Web of Science were last searched on 16 April 2023 for studies on DMT that compared the clinical outcomes between APM and ET. The subjective outcomes of the comparison include the Knee Injury and Osteoarthritis Outcome Score (KOOS), which consists of five sub-scales: pain, symptoms, activities of daily living (ADL), sport and recreation (Sport/recreation), and quality of life (QOL). The objective outcome includes knee osteoarthritis progression. RESULTS: We identified 6 potentially eligible trials, including 1078 participants, from the literature search. ET showed a lower risk of knee osteoarthritis progression than APM (RR, 1·27; 95%CI 1·05 to 1·53). There were no statistically significant differences in the KOOS-pain, KOOS-symptoms, KOOS-ADL, KOOS-Sport/recreation, and KOOS-QOL between the two treatment methods. CONCLUSION: For the treatment of DMT, ET showed a lower risk of knee osteoarthritis progression than APM. ET and APM had comparable effects on subjective outcomes including pain management and knee function. Therefore, it is not recommended to use APM but rather recommended to use ET for treating APM.
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Terapia por Exercício , Meniscectomia , Osteoartrite do Joelho , Lesões do Menisco Tibial , Humanos , Atividades Cotidianas , Artroscopia/métodos , Progressão da Doença , Terapia por Exercício/métodos , Seguimentos , Meniscectomia/métodos , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Lesões do Menisco Tibial/cirurgia , Lesões do Menisco Tibial/terapia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: There was controversy surrounding the optimal thromboprophylaxis strategy for coronavirus disease 2019 (COVID-19) patients. This included debates on the dosage of anticoagulants for thromboembolism prophylaxis, the requirement for additional antiplatelet therapy, and the necessity of prophylaxis for outpatients and postdischarge. To explore this, the authors performed a meta-analysis of randomized controlled trials. METHODS: PubMed, Cochrane Library, Embase, and Web of Science were last searched on 26 July 2023 for studies comparing the effect of different dose of anticoagulation, additional antiplatelet, and postdischarge prophylaxis for COVID-19 patients. The results of eligible studies were analyzed in terms of thromboembolism events, major bleeding and all-cause mortality during follow-up. RESULTS: Our study included a total of 25 randomized controlled trials, involving 17 911 patients. Our results revealed that, compared to prophylactic dose, therapeutic dose showed lower thrombotic risk (RR, 0.66; 95% CI: 0.45-0.96) but had similar major bleeding risk for critically ill patients with COVID-19. On the other hand, intermediate dose and prophylactic dose demonstrated similar thromboembolism risk and major bleeding risk. For noncritically ill patients with COVID-19, therapeutic dose of anticoagulants was associated with lower thrombotic risk (RR, 0.50; 95% CI: 0.34-0.72) but, at the same time, increased the risk of major bleeding (RR, 2.01; 95% CI: 1.22-3.33). However, intermediate dose showed lower thromboembolism risk (RR, 0.38; 95% CI: 0.21-0.69) while maintaining a similar major bleeding risk. In critically ill patients, additional antiplatelet therapy showed similar thromboembolism, major bleeding risk, and mortality when compared to no treatment. For outpatients, additional prophylactic anticoagulation showed similar thromboembolism, major bleeding risk, and mortality when compared to no treatment. For postdischarge patients, postdischarge prophylaxis reduced thromboembolism risk (RR, 0.49; 95% CI: 0.31-0.76) but increased major bleeding risk (RR, 2.63; 95% CI: 1.13-6.14). CONCLUSION: For noncritically ill patients, therapeutic dose prophylactic anticoagulation significantly reduced venous thromboembolism but increases major bleeding risk. Intermediate dose effectively lowered venous thromboembolism without raising major bleeding risk. The optimal dose and need for additional antiplatelet therapy in critically ill patients, as well as the necessity of prophylactic anticoagulation in outpatient and postdischarge patients, required further investigation and confirmation through rigorous evidence studies.
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Anticoagulantes , COVID-19 , Inibidores da Agregação Plaquetária , Ensaios Clínicos Controlados Aleatórios como Assunto , Tromboembolia , Humanos , COVID-19/prevenção & controle , COVID-19/complicações , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/uso terapêutico , Tromboembolia/prevenção & controle , Tromboembolia/etiologia , Hemorragia/induzido quimicamente , Alta do Paciente , SARS-CoV-2RESUMO
The purpose of this study was to reveal the current trends and preferences of Chinese orthopedic surgeons regarding anterior cruciate ligament (ACL) reconstruction through a nationwide web-based survey conducted in China. The survey questionnaire was distributed via WeChat to the chairmen of provincial orthopedic and sports medicine organizing committees in China, who then shared it in their respective WeChat workgroups. The questionnaire consisted of 52 multiple-choice questions covering 8 sections. Data collection was implemented by Questionnaire Star. A total of 812 valid questionnaires were returned: 94.21% of the respondents preferred single-bundle reconstruction of ACL, while 61.70% preferred autogenous semitendinosus plus gracilis reconstruction; 76.35% of the respondents preferred establishing the femoral tunnel first, while 47.29% preferred establishing the femoral tunnel through a medial auxiliary approach; and 85.10% of the respondents recommended patients to undergo surgery within 3 months after ligament injury. Besides, the vast majority of respondents chose to retain the ligamentous remnant bundle (92.98%) and recommended routine use of knee braces postoperatively (94.09%). It is recommended to perform arthroscopic single-bundle ACL reconstruction with the remnant preserving technique using a hamstring autograft within 3 months of ACL rupture, with support of postoperative functional braces.
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Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Cirurgiões Ortopédicos , Humanos , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Inquéritos e Questionários , Reconstrução do Ligamento Cruzado Anterior/métodosRESUMO
Massive rotator cuff tears are a huge challenge for orthopaedic surgeons, as the patients may be in need of multiple operations, even including reverse total shoulder arthroplasty. The various repair methods for the rotator cuff, such as partial rotator cuff repair, patch-augmented rotator cuff repair, bridging rotator cuff reconstruction with graft interposition, tendon transfer, and superior capsular reconstruction, have always been the focus of research. During surgical intervention for failed rotator cuff repairs, complexity of tears, poor tissue quality, retained hardware, and adhesions are the problems routinely encountered. In this Technical Note, we describe the technique of interposition grafting using fascia lata autograft to reconstruct the rotator cuff after failed primary repair.
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In the field of inter-satellite laser communication, achieving high-quality communication and compensating for the Doppler frequency shift caused by relative motion necessitate lasers with narrow linewidths, low phase noise, and the ability to achieve mode-hop-free tuning within a specific range. To this end, this paper investigates a novel external cavity diode laser (ECDL) with a frequency-selective F-P etalon structure, leveraging the external cavity F-P etalon structure in conjunction with an auxiliary filter to achieve single longitudinal mode selection. The laser undergoes linewidth testing using a delayed self-heterodyne beating method, followed by the testing of its phase noise and frequency noise characteristics using a noise analyzer, yielding beat spectra and noise power spectral density profiles. Furthermore, the paper introduces an innovative bidirectional temperature-scanning laser method to achieve optimal laser-operating point selection and mode-hop-free tuning. The experimental results showcase that the single longitudinal mode spectral side-mode suppression ratio (SMSR) is around 70 dB, and the output power exceeds 10 mW. Enhancing the precision of the F-P etalon leads to a more pronounced suppression of low-frequency phase noise, reducing the Lorentzian linewidth from the initial 10 kHz level to a remarkable 5 kHz level. The bidirectional temperature-scanning laser method not only allows for the selection of the optimal operating point but also enables mode-hop-free tuning within 160 pm.
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Background: Several techniques have been used by surgeons for anatomic tibial tunnel placement in anterior cruciate ligament (ACL) reconstruction, including the ACL stump positioning (ASP) technique and the tibial spine positioning (TSP) technique. Purpose/Hypothesis: The purpose of this study was to evaluate whether bony landmarks (medial and lateral tibial spine [MLTS]) can be a reliable reference for improving the accuracy of tibial tunnel placement in anatomic single-bundle ACL reconstruction compared with the ACL stump. It was hypothesized that the MLTS would not be a reliable bony landmark for tibial tunnel placement. Study Design: Cohort study; Level of evidence, 3. Methods: The 3-dimensional computed tomography images of 111 patients who underwent ACL reconstruction between 2020 and 2021 were included in this study. For tibial tunnel placement, the ASP technique was used in 49 patients, and the TSP technique was used in 62 patients. The 3-dimensional computed tomography images were reconstructed to enable measurements of the locations of the MLTS and tunnel center based on a grid method. Statistical analysis was conducted to compare the MLTS location and tibial tunnel position as well as the accuracy (mean distance of each actual location from the anatomic center) and precision (standard deviation of the accuracy, indicating the reproducibility of the tunnel position) of the tunnel position between the ASP and TSP groups. Results: Significant differences were observed between the ASP and TSP groups in terms of the tibial tunnel position on the mediolateral axis (46.7% ± 2.0% vs 45.9% ± 2.2%, respectively; P = .034), while no significant differences were found in terms of the accuracy (4.1% vs 4.6%, respectively; P = .259) or precision (2.1% vs 2.1%, respectively; P = .259) of tibial tunnel positioning between the 2 groups. Conclusion: In anatomic single-bundle ACL reconstruction, the use of the MLTS for tibial tunnel placement achieved comparable accuracy and precision compared with the use of ACL remnants, supporting its role as a reliable bony landmark in tibial tunnel positioning.
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There are many studies examining the dimensions of the anterior cruciate ligament (ACL) in children. The correlations between the ACL size in children and other parameters are not well understood. To detect the correlations between the ACL size in children and other parameters including age, gender, bone and soft tissue parameters through measurements on MRI images, and to establish prediction models for the ACL size. A total of 99 patients who underwent MRI scan were included (39 girls, 60 boys; mean age, 13.01â ±â 3.94; range of age, 4 to 18). The following measurements were taken on MRI images by 2 observers: ACL length, ACL width, posterior cruciate ligament (PCL) length, the distance from the most anterior aspect of the tibial epiphysis to the anterior aspect of the ACL tibial insertion (AATI), the distance from the most anterior aspect of the tibial epiphysis to the posterior aspect of the ACL tibial insertion (APTI), and the tibial anteroposterior diameter (AP). Correlations between these measurements and the patients' gender and age were investigated, and univariate and multiple linear regression models were established accordingly. Before 13 years old, the ACL length was significantly correlated with the tibial anteroposterior diameter and age (R2â =â 0.872, Pâ <â .001), and there were no statistically significant gender differences. After 13 years old, the ACL length was significantly correlated with the PCL length and APTI in males (R2â =â 0.443, Pâ <â .001), and with the PCL length in females (R2â =â 0.443, Pâ <â .001). In children under 13 years old, there was no significant gender difference in ACL length, and the tibial anteroposterior diameter and age were found to be important indicators in assessing the ACL size. After 13 years old, a significant gender difference in ACL length was observed, and the ACL length was found to be weakly correlated with age and bone parameters. In order to accurately evaluate the ACL size in children aged 13 years and above, it is necessary to refer to the dimensions of the ACL on the collateral side.
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Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Ligamento Cruzado Posterior , Masculino , Feminino , Humanos , Criança , Adolescente , Pré-Escolar , Ligamento Cruzado Anterior/diagnóstico por imagem , Ligamento Cruzado Anterior/cirurgia , Articulação do Joelho/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Imageamento por Ressonância Magnética/métodos , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/cirurgiaRESUMO
Heavy metal pollution in wastewater poses a grave danger to the environment and the human body. Pumice is a mineral with abundant reserves and low prices, and its prospect of heavy metal adsorbent is very broad. In this work, we modified pumice with basic magnesium carbonate nanosheets by a convenient hydrothermal synthesis. The adsorption capacity of heavy metals is greatly improved. The effects of different pH and adsorption dosages are investigated. All the optimum pH values for Cu2+, Pb2+, and Cd2+ are 5. The adsorption of three kinds of ions conforms to the quasi-second-order adsorption kinetics model. The theoretical adsorption capacities of Cu2+, Pb2+, and Cd2+, which are calculated by the Langmuir model, are 235.29 mg/L, 595.24 mg/L, and 370.34 mg/L, respectively. The adsorption of Cu2+ and Cd2+ fit the Langmuir model better. The Freundlich model is fitted well with the adsorption of Pb2+. In the experiment simulating real wastewater, the adsorption capacity of heavy metals is not affected. It also shows good reusability in three regeneration cycles. And Mg5(CO3)4(OH)2·4H2O@pumice adsorption column showed the good removal efficiency of three heavy metals at different concentrations and different spatial velocities in the column experiment. Thus, it is believed that the Mg5(CO3)4(OH)2·4H2O@pumice is a promising adsorbent for the efficient removal of heavy metals.
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Metais Pesados , Poluentes Químicos da Água , Humanos , Cádmio , Águas Residuárias , Adsorção , Chumbo , Poluentes Químicos da Água/análise , Metais Pesados/análise , Cinética , Concentração de Íons de HidrogênioRESUMO
BACKGROUND: Vitamin D (VitD) has been shown to be important for the immune response of the respiratory system, but the preventive and therapeutic effects of vitamin D supplementation on SARS-CoV-2 infection are controversial. This study aimed to determine the role of vitamin D supplementation in the prevention and treatment of SARS-CoV-2 infection through a meta-analysis of randomized controlled trials. METHODS: The databases of PubMed, Cochrane Library, Embase, Web of Science and Google Scholar were searched systematically from inception to April 17,2023 to identify trials involving a randomized comparison of vitamin D supplementation versus non-vitamin D supplementation for SARS-CoV-2 infection prevention or treatment. RESULTS: We retrieved 25 eligible trials, including 8128 participants. Four trials compared the preventive effects of vitamin D supplementation on SARS-CoV-2 infection, and the results (RR 0.31; 95%CI 0.07 to 1.32) were inconclusive. Regarding the treatment of SARS-CoV-2 infection with vitamin D supplementation, it was found that vitamin D supplementation could significantly reduce the rates of ICU admission (RR 0.63; 95%CI 0.44 to 0.89) and mechanical ventilation (RR 0.58; 95%CI 0.39 to 0.84), but had no statistically significant effect on mortality. However, in subgroup analyses based on the patients' specific conditions, vitamin D supplementation significantly reduced the mortality in patients with vitamin D deficiency (RR 0.76; 95%CI 0.58 to 0.98). CONCLUSION: Vitamin D supplementation may have some beneficial impact on the severity of illness caused by SARS-CoV-2, particularly in VitD deficient patients, but further studies are still needed.
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COVID-19 , Deficiência de Vitamina D , Humanos , Vitamina D/uso terapêutico , COVID-19/prevenção & controle , SARS-CoV-2 , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitaminas/uso terapêutico , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/prevenção & controle , Suplementos NutricionaisRESUMO
Gut dysbiosis contributes to Alzheimer's disease (AD) pathogenesis, and Bacteroides strains are selectively elevated in AD gut microbiota. However, it remains unknown which Bacteroides species and how their metabolites trigger AD pathologies. Here we show that Bacteroides fragilis and their metabolites 12-hydroxy-heptadecatrienoic acid (12-HHTrE) and Prostaglandin E2 (PGE2) activate microglia and induce AD pathogenesis in neuronal C/EBPß transgenic mice. Recolonization of antibiotics cocktail-pretreated Thy1-C/EBPß transgenic mice with AD patient fecal samples elicits AD pathologies, associated with C/EBPß/Asparaginyl endopeptidase (AEP) pathway upregulation, microglia activation, and cognitive disorders compared to mice receiving healthy donors' fecal microbiota transplantation (FMT). Microbial 16S rRNA sequencing analysis shows higher abundance of proinflammatory Bacteroides fragilis in AD-FMT mice. Active components characterization from the sera and brains of the transplanted mice revealed that both 12-HHTrE and PGE2 activate primary microglia, fitting with poly-unsaturated fatty acid (PUFA) metabolites enrichment identified by metabolomics. Strikingly, recolonization with live but not dead Bacteroides fragilis elicited AD pathologies in Thy1-C/EBPß transgenic mice, so did 12-HHTrE or PGE2 treatment alone. Collectively, our findings support a causal role for Bacteroides fragilis and the PUFA metabolites in activating microglia and inducing AD pathologies in Thy1- C/EBPß transgenic mice.