RESUMO
In oncology/hematology early phase clinical trials, efficacies were often observed in terms of response rate, depth, timing, and duration. However, the true clinical benefits that eventually support registrational purpose are progression-free survival (PFS) and/or overall survival (OS), the follow-up of which are typically not long enough in early phase trials. This gap imposes challenges in strategies for late phase drug development. In this article, we tackle the question by leveraging published study to establish a quantitative link between early efficacy outcomes and late phase efficacy endpoints. We used solid tumor cancer as disease model. We modeled the disease course of a RECISTv1.1 assessed solid tumor with a continuous Markov chain (CMC) model. We parameterize the transition intensity matrix of a CMC model based on published aggregate-level summary statistics, and then simulate subject-level time-to-event data. The simulated data is shown to have good approximation to published studies. PFS and/or OS could be predicted with the transition intensity matrix modified given clinical knowledge to reflect various assumptions on response rate, depth, timing, and duration. The authors have built a R shiny application named PubPredict, the tool implements the algorithm described above and allows customized features including multiple response levels, treatment crossover and varying follow-up duration. This toolset has been applied to advise phase 3 trial design when only early efficacy data are available from phase 1 or 2 studies.
Assuntos
Neoplasias , Humanos , Intervalo Livre de Doença , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND AND PURPOSE: Choline pathway nutrients, including choline and betaine, are reported to exert antidepressant effects. However, there is little population-based evidence on the relationships between circulating choline and betaine and poststroke depression (PSD). We aimed to prospectively explore the associations between plasma choline and betaine and depression after ischemic stroke. METHODS: This study was based on the China Antihypertensive Trial in Acute Ischemic Stroke. A total of 612 participants with plasma choline and betaine concentrations were included in the analysis. The study outcome was depression 3 months after ischemic stroke. Logistic regression models were performed to estimate the relationships between plasma choline and betaine and the risk of PSD. Risk reclassification and calibration of models with choline or betaine were analyzed. RESULTS: Patients with PSD had lower choline and betaine levels than those without PSD (p < 0.05). Compared with tertile 1, the multivariable-adjusted odds ratios (95% CIs) for tertile 3 of choline and betaine were 0.54 (0.35-0.83) and 0.59 (0.38-0.92), respectively. Per 1 SD increase in choline or betaine was associated with a 25% (95% CI 9%-37%) or an 19% (95% CI 3%-32%) decreased risk of PSD, respectively. Furthermore, the addition of choline or betaine to the established risk factors model improved the risk reclassification for PSD, as shown by an increase in the net reclassification index and integrated discrimination improvement (all p < 0.05). CONCLUSIONS: Patients with elevated levels of choline and betaine had a lower risk of depression after acute ischemic stroke, suggesting the protective significance of choline pathway nutrients for PSD.
Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Colina , Depressão/etiologia , Humanos , Nutrientes , Fatores de Risco , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND: Itaconic acid (IA) is a versatile platform chemical widely used for the synthesis of various polymers and current methods for IA production based on Aspergillus terreus fermentation are limited in terms of process efficiency and productivity. To construct more efficient IA production strains, A. niger was used as a chassis for engineering IA production by assembling the key components of IA biosynthesis pathways from both A. terreus and Ustilago maydis. RESULTS: Recombinant A. niger S1596 overexpressing the A. terreus IA biosynthesis genes cadA, mttA, mfsA produced IA of 4.32 g/L, while A. niger S2120 overexpressing the U. maydis IA gene cluster adi1, tad1, mtt1, itp1 achieved IA of 3.02 g/L. Integration of the two IA production pathways led to the construction of A. niger S2083 with IA titers of 5.58 g/L. Increasing cadA copy number in strain S2083 created strain S2209 with titers of 7.99 g/L and deleting ictA to block IA degradation in S2209 created strain S2288 with IA titers of 8.70 g/L. Overexpressing acoA to enhance the supply of IA precursor in strain S2288 generated strain S2444 with IA titers of 9.08 g/L in shake flask. CONCLUSION: Recombinant A. niger overexpressing the U. maydis IA biosynthesis pathway was capable of IA accumulation. Combined expression of the two IA biosynthesis pathways from A. terreus and U. maydis in A. niger resulted in much higher IA titers. Furthermore, increasing cadA copy number, deleting ictA to block IA degradation and overexpressing acoA to enhance IA precursor supply all showed beneficial effects on IA accumulation.
Assuntos
Aspergillus niger , Succinatos , Aspergillus , Aspergillus niger/genética , Aspergillus niger/metabolismo , Basidiomycota , Succinatos/metabolismoRESUMO
Intestinal absorption liquid was prepared by using everted intestinal sac method; meanwhile, its recipes were decomposed or restructured. Platelet aggregation activity was examined by biochemical tests and a microplate reader. One or more kinds of Chinese medicines which displayed inhibiting activity in Naoxintong Capsules were screened through separation and combination of prescription. The results showed that Naoxintong Capsules could inhibit ADP-induced platelet aggregation. Recipe decomposition and restructuring results showed that Salviae Miltiorrhizae Radix et Rhizoma, Paeoniae Radix Rubra, Cinnamomi Ramulus and Hirudo were the main effective medicines in inhibiting platelet aggregation. Furthermore, Cinnamomi Ramulus played a vital role in inhibiting activity among those four kinds of Chinese medicines. Coumarin derived from intestinal absorption liquid of Cinnamomi Ramulus had inhibiting activity in the range of 50-200 µmol·L⻹, and other ingredients such as cinnamyl alcohol and cinnamaldehyde also had inhibiting activities. In conclusion, Salviae Miltiorrhizae Radix et Rhizoma, Paeoniae Radix Rubra, Cinnamomi Ramulus and Hirudo are the main components for inhibiting ADP-induced platelet aggregation, and Cinnamomi Ramulus has the most strongest inhibiting activity in Naoxintong Capsules.
Assuntos
Medicamentos de Ervas Chinesas , Agregação Plaquetária , Difosfato de Adenosina , Cápsulas , Absorção IntestinalRESUMO
Highly crystalline graphitic carbon nitride (g-C3 N4 ) with decreased structural imperfections benefits from the suppression of electron-hole recombination, which enhances its hydrogen generation activity. However, producing such g-C3 N4 materials by conventional heating in an electric furnace has proven challenging. Herein, we report on the synthesis of high-quality g-C3 N4 with reduced structural defects by judiciously combining the implementation of melamine-cyanuric acid (MCA) supramolecular aggregates and microwave-assisted thermolysis. The g-C3 N4 material produced after optimizing the microwave reaction time can effectively generate H2 under visible-light irradiation. The highest H2 evolution rate achieved was 40.5â µmol h-1 , which is two times higher than that of a g-C3 N4 sample prepared by thermal polycondensation of the same supramolecular aggregates in an electric furnace. The microwave-assisted thermolysis strategy is simple, rapid, and robust, thereby providing a promising route for the synthesis of high-efficiency g-C3 N4 photocatalysts.
RESUMO
To analyze the composition regularity of Carthami Flos-containing prescriptions of the Drug Standards of Ministry of Health of People's Republic of China-Traditional Chinese Medicine Preparations (the ministerial standards for Traditional Chinese Medicine) based on the traditional Chinese medicine inheritance support system (TCMISS, RZDZ No. 0389952). Efforts were made to identify 331 prescriptions containing Carthami Flos and summarize 16 attending functions and 10 commonly used drug combinations. Three commonly used drug combinations were selected for an in-depth analysis on Carthami Flos's combined administration regularity. Based on Carthami Flos's attending functions, its effects in paralysis, traumatic injuries and dysmenorrheal were compared to analyze Carthami Flos's core drug combinations for treating different diseases. The regularity of clinical administration and the characteristics of commonly used drug combinations were summarized to provide reference for Carthami Flos's clinical application and new ideas for new drug R&D. Carthami Flos prescriptions was mainly used to treat blood stasis and pain and mostly combined with drugs that could activate blood, promote the circulation of qi and dispel pathogenic wind to treat Qi-stagnation and blood stasis caused by various pathogenic factors such as wind, cold and dampness.
Assuntos
Carthamus/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Flores/química , Ensaios Clínicos como Assunto , Prescrições de Medicamentos , Tratamento Farmacológico , HumanosRESUMO
While the recent prediction and observation of magnetic skyrmions bears inspiring promise for next-generation spintronic devices, how to detect and track their position becomes an important issue. In this work, we investigate the spin transport in a two-dimensional magnetic nanoribbon with the Hall-bar geometry in the presence of Rashba spin-orbit coupling and magnetic skyrmions. We employ the Kwant tight-binding code to compute the Hall conductance and local spin-polarized current density. We consider two versions of the model: One with single skyrmion and one with two separate skyrmions. It is found that the size and position of the skyrmions strongly modulate the Hall conductance near the Hall-bar position. The geometry of the Hall bar also has a strong influence on the Hall conductance of the system. With the decreasing of the width of Hall leads, the peak of Hall conductance becomes sharper. We also show the spatial distribution of the spin-polarized current density around a skyrmion located at different positions. We extend this study toward two separate skyrmions, where the Hall conductance also reveals a sizable dependence on the position of the skyrmions and their distance. Our numerical analysis offers the possibility of electrically detecting the skyrmion position, which could have potential applications in ultrahigh-density storage design.
RESUMO
Introduction: Donepezil enhances the function of cholinergic nerves by increasing the concentration of acetylcholine, thereby improving clinical symptoms in patients with Alzheimer's disease (AD). However, the neural mechanisms of how donepezil modulates the effective connectivity (EC) network of cholinergic system in AD patients remain unknown. We speculated that the effective network of the cholinergic system changes in AD patients after donepezil intervention. Methods: We employed resting-state functional magnetic resonance imaging and Granger causality analysis approach to explore changes in the effective connectivity network of the basal forebrain in AD patients before and after donepezil intervention. This study included 32 participants, including 16 healthy controls (HCs) and 16 AD patients. In a 3T MRI scanner, the 16 AD patients were scanned before and after the donepezil intervention. To compare EC differences between the three groups of participants, ANOVA and post-hoc t-tests analysis were employed. Results: Compared to baseline status, AD patients after donepezil intervention had an increased EC from left middle occipital gyrus to right medial septum/diagonal bands. Compared to HCs, AD patients after donepezil intervention had an increased EC from right inferior frontal gyrus/orbit part to right medial septum/diagonal bands, AD patients before donepezil intervention had a reduced EC from right precuneus to right medial septum/diagonal bands. A significant positive correlation was found between EC values in right precuneus and Mini-Mental State Examination in pre-intervention AD patients (r = 0.7338, p = 0.0012). Discussion: Our study showed that effective connectivity of brain regions associated with the default mode network in the cholinergic pathway was enhanced after donepezil intervention. The results of this study will help us to better understand the neural mechanisms of donepezil intervention in AD and to find clinical targets for intervention.
RESUMO
OBJECTIVE: To study the absorption characteristics of four components from Naoxintong capsule in intestines. METHOD: In vitro everted gut sac method was adopted for preparing the intestinal absorption solution of Naoxintong capsule. UPLC was used to detect the content of chemical components in different intestinal segments, and comparing the results with the absorption of chemical components of Naoxintong capsule in each intestinal segment. The time-accumulative absorption curve was drawn to observe the changes in the accumulative absorption concentration with time. RESULT: Four ingredients of Naoxintong capsule can be detected in intestinal absorption solution, they are ferulic acid, paeoniflorin, salvianolic acid B and hydroxysafflor yellow A. Specifically, the accumulative absorption concentrations of ferulic acid, salvianolic acid B and paeoniflorin in ileum and rear jejunum segments were higher than that in front and middle jejunum segments; the absorption of ferulic acid, paeoniflorin, salvianolic acid B and hydroxysafflor yellow A did not reach saturated conditions in 3 hours. CONCLUSION: Ferulic acid, paeoniflorin, salvianolic acid B and hydroxysafflor yellow A are absorbed in the whole intestine. Ferulic acid, paeoniflorin and salvianolic acid B may be absorbed in specific segments.
Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Absorção Intestinal , Animais , Cápsulas , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos TestesRESUMO
The spiking neural network (SNN), as a promising brain-inspired computational model with binary spike information transmission mechanism, rich spatially-temporal dynamics, and event-driven characteristics, has received extensive attention. However, its intricately discontinuous spike mechanism brings difficulty to the optimization of the deep SNN. Since the surrogate gradient method can greatly mitigate the optimization difficulty and shows great potential in directly training deep SNNs, a variety of direct learning-based deep SNN works have been proposed and achieved satisfying progress in recent years. In this paper, we present a comprehensive survey of these direct learning-based deep SNN works, mainly categorized into accuracy improvement methods, efficiency improvement methods, and temporal dynamics utilization methods. In addition, we also divide these categorizations into finer granularities further to better organize and introduce them. Finally, the challenges and trends that may be faced in future research are prospected.
RESUMO
Crystalline solid dispersions (CSDs) represent a thermodynamically stable system capable of effectively reducing the crystallite size of drugs, thereby enhancing their solubility and bioavailability. This study uses flavonoid drugs with the same core structures but varying numbers of hydroxyl groups as model drugs and poloxamer 188 as a carrier to explore the intrinsic relationships between drug-polymer interactions, crystallite size, and in vitro dissolution behavior in CSDs. Initially, we investigate the interactions between flavonoid drugs and P188 by calculating Hansen solubility parameters, determination of Flory-Huggins interaction parameters, and other methods. Subsequently, we explore the crystallization kinetics of flavonoid drugs and P188 in CSD systems using polarized optical microscopy and powder X-ray diffraction. We monitor the domain size and crystallite size of flavonoids in CSDs through powder X-ray diffraction and a laser-particle-size analyzer. Finally, we validate the relationship between crystallite size and in vitro dissolution behavior through powder dissolution. The results demonstrate that, as the number of hydroxyl groups increases, the interactions between drugs and polymers become stronger, making drug crystallization in the CSD system less likely. Consequently, reductions in crystalline domain size and crystallite size become more pronounced, leading to a more significant enhancement in drug dissolution.
RESUMO
INTRODUCTION: Cancer-related fatigue (CRF) is one of the most common and debilitating side effects experienced by patients with breast cancer (BC) during postoperative chemotherapy. Family-involvement combined aerobic and resistance exercise has been introduced as a promising non-pharmacological intervention for CRF symptom relief and improving patients' muscle strength, exercise completion, family intimacy and adaptability and quality of life. However, evidence for the practice of home participation in combined aerobic and resistance exercise for the management of CRF in patients with BC is lacking. METHODS AND ANALYSIS: We present a protocol for a quasi-randomised controlled trial involving an 8-week intervention. Seventy patients with BC will be recruited from a tertiary care centre in China. Participants from the first oncology department will be assigned to the family-involvement combined aerobic and resistance exercise group (n=28), while participants from the second oncology department will be assigned to the control group that will receive standard exercise guidance (n=28). The primary outcome will be the Piper Fatigue Scale-Revised (R-PFS) score. The secondary outcomes will include muscle strength, exercise completion, family intimacy and adaptability and quality of life, which will be evaluated by the stand-up and sit-down chair test, grip test, exercise completion rate, Family Adaptability and Cohesion Scale, Second Edition-Chinese Version (FACESâ ¡-CV) and Functional Assessment of Cancer Therapy -Breast (FACT-B) scale. Analysis of covariance will be applied for comparisons between groups, and paired t-tests will be used for comparison of data before and after exercise within a group. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University (PJ-KS-KY-2021-288). The results of this study will be published via peer-reviewed publications and presentations at conferences. TRAIL REGISTRATION NUMBER: ChiCTR2200055793.
Assuntos
Neoplasias da Mama , Treinamento Resistido , Feminino , Humanos , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Terapia por Exercício/métodos , Fadiga/etiologia , Fadiga/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Apoio FamiliarRESUMO
Bacterial therapy has become a key strategy against intestinal infectious diseases in recent years. Moreover, regulating the gut microbiota through traditional fecal microbiota transplantation and supplementation of probiotics faces controllability, efficacy, and safety challenges. The infiltration and emergence of synthetic biology and microbiome provide an operational and safe treatment platform for live bacterial biotherapies. Synthetic bacterial therapy can artificially manipulate bacteria to produce and deliver therapeutic drug molecules. This method has the advantages of solid controllability, low toxicity, strong therapeutic effects, and easy operation. As an essential tool for dynamic regulation in synthetic biology, quorum sensing (QS) has been widely used for designing complex genetic circuits to control the behavior of bacterial populations and achieve predefined goals. Therefore, QS-based synthetic bacterial therapy might become a new direction for the treatment of diseases. The pre-programmed QS genetic circuit can achieve a controllable production of therapeutic drugs on particular ecological niches by sensing specific signals released from the digestive system in pathological conditions, thereby realizing the integration of diagnosis and treatment. Based on this as well as the modular idea of synthetic biology, QS-based synthetic bacterial therapies are divided into an environmental signal sensing module (senses gut disease physiological signals), a therapeutic molecule producing module (plays a therapeutic role against diseases), and a population behavior regulating module (QS system). This review article summarized the structure and function of these three modules and discussed the rational design of QS gene circuits as a novel intervention strategy for intestinal diseases. Moreover, the application prospects of QS-based synthetic bacterial therapy were summarized. Finally, the challenges faced by these methods were analyzed to make the targeted recommendations for developing a successful therapeutic strategy for intestinal diseases.
Assuntos
Microbioma Gastrointestinal , Enteropatias , Humanos , Percepção de Quorum/genética , Bactérias , Microbioma Gastrointestinal/genética , Redes Reguladoras de GenesRESUMO
Objectives: The impact of non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumor necrosis factor inhibitors (TNFi) on the outcomes of mild-moderate COVID-19 in patients with ankylosing spondylitis (AS) remains unclear. This study aimed to evaluate the effects of NSAIDs, csDMARDs, and TNFi on AS patients with mild-moderate COVID-19. Methods: This cohort study utilized patient-reported PCR/antigen tests to determine the occurrence of COVID-19 and assessed clinical manifestations to determine its severity. The study focused on two primary outcomes: an increased number of COVID-19 symptoms and a prolonged disease course (longer than 10 or 28 days). Modified Poisson regression was performed to analyze the association between exposures and outcomes. Results: A total of 521 patients were included in the analysis. The median age was 34.8 (inter-quartile range: 27.2-46.7), with 420 (80.6%) being men. Among the patients, 52 (10.0%) had comorbidities and 443 (85%) had been vaccinated. After adjusting for confounding factors, there was no significant association between csDMARDs or TNFi and the presence of more than 5 symptoms in mild-moderate COVID-19 (adjusted relative risk (RRa) 1.08, 95% CI: 0.84-1.40 or 1.09, 0.92-1.29 for csDMARDs or TNFi, respectively), whereas the prevalence of experiencing more than 5 symptoms increased in patients with NSAID monotherapy (RRa 1.22, 95% CI: 1.01-1.46). Similarly, there was no significant association with having more than 10 symptoms (RRa 0.65, 95% CI: 0.26-1.64; 0.95, 0.36-2.54; and 1.01, 0.53-1.91 for NSAIDs, csDMARDs, and TNFi, respectively). Patients who had pre-existing use of NSAIDs, csDMARDs and TNFi had similar odds of experiencing a disease course longer than 10 days (RRa 1.17, 95% CI: 0.82-1.66; 1.18, 0.78-1.77; and 1.22, 0.92-1.63 for NSAIDs, csDMARDs, and TNFi, respectively) and longer than 28 days (RRa 0.94, 95% CI: 0.31-2.81; 0.97, 0.25-3.74 and 1.05, 0.44-2.49, respectively) compared to those not using medication. Conclusion: AS patients treated with csDMARDs or TNFi did not show inferior outcomes in terms of symptom burden or recovery compared to those not using medication in mild-moderate COVID-19. The observed inverse association between pre-existing NSAIDs use and COVID-19 symptom burden in AS deserves further investigation.
RESUMO
AIMS: Weight reduction is fundamental for the management and remission of diabetes. We aimed to assess ethnic differences in the effects of lifestyle weight-loss interventions on HbA1c levels in overweight or obese adults with type 2 diabetes mellitus (T2DM). METHODS: We systematically searched PubMed/MEDLINE and Web of Science online databases up to 31 Dec 2022. Randomized controlled trials using lifestyle weight-loss interventions in overweight or obese adults with T2DM were selected. We performed subgroup analyses to explore the heterogeneity across different ethnicities (Asians, White/Caucasians, Black/Africans and Hispanics). A random effects model was applied to calculate weighted mean difference (WMD) with 95% confidence interval (CI). RESULTS: Thirty studies including 7580 subjects from different ethnicities were identified according to the predefined inclusion and exclusion criteria. HbA1c levels were significantly reduced by lifestyle weight-loss intervention. Notably, a significantly beneficial effect on HbA1c was observed in White/Caucasians (WMD = -0.59, 95% CI: -0.90, -0.28, P < 0.001) and Asians (WMD = -0.48, 95% CI: -0.63, -0.33, P < 0.001), but not in the Black/African or Hispanic group (both P > 0.05). The findings remained essentially unchanged in the sensitivity analysis. CONCLUSIONS: Lifestyle weight-loss interventions had distinct beneficial effects on HbA1c levels in different ethnic groups with T2DM, especially in Caucasians and Asians.
Assuntos
Diabetes Mellitus Tipo 2 , Sobrepeso , Adulto , Humanos , Sobrepeso/terapia , Diabetes Mellitus Tipo 2/terapia , Hemoglobinas Glicadas , Etnicidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Obesidade/terapia , Estilo de Vida , Redução de PesoRESUMO
Multidrug-resistance (MDR) Pseudomonas aeruginosa (P. aeruginosa) is a lethal gram-negative pathogen causing hospital-acquired and ventilator-associated pneumonia, which is difficult to treat. Our previous studies confirmed that baicalin, an essential bioactive component in Scutellaria baicalensis Georgi, exhibited anti-inflammatory effects in an acute pneumonia rat model induced by MDR P. aeruginosa. However, this effect of baicalin in constrast its low bioavailability, and its mechanism of action is still unknown. Thus, this study investigated whether the therapeutic effects of baicalin against MDR P. aeruginosa acute pneumonia are owing to the regulation of gut microbiota and their metabolites using pyrosequencing of the 16S rRNA genes in rat feces and metabolomics. As a result, baicalin attenuated the inflammation by acting directly on neutrophils and regulated the production of the inflammatory cytokines TNF-α, IL-1ß, IL-6, and IL-10. The mechanisms were through down-regulation of TLR4 and inhibition of NF-κB. Furthermore, pyrosequencing of the 16S rRNA genes in rat feces revealed that baicalin regulated the composition of gut microbial communities. At the genus level, baicalin efficiently increased the abundance of Ligilactobacillus, Lactobacillus and Bacteroides, but decreased the abundance of Muribaculaceae and Alistipes. Further, arginine biosynthesis was analyzed as the core pathway regulated by baicalin via combination with predicting gut microbiota function and targeted metabolomics. In conclusion, this study has demonstrated that baicalin relieved inflammatory injury in acute pneumonia rat induced by MDR P. aeruginosa via arginine biosynthesis associated with gut microbiota. Baicalin could be a promising and effective adjunctive therapy for lung inflammation caused by MDR P. aeruginosa infection.
Assuntos
Pneumonia , Pseudomonas aeruginosa , Ratos , Animais , RNA Ribossômico 16S , Inflamação/tratamento farmacológico , Pneumonia/tratamento farmacológico , Flavonoides/farmacologia , Arginina/farmacologiaRESUMO
Background: Patients diagnosed with influenza and upper respiratory tract infections (URTIs) have similar clinical manifestations and biochemical indices and a low detection rate of viral pathogens, mixed infection with diverse respiratory viruses, and targeted antiviral treatment difficulty in the early stage. According to the treatment strategy of "homotherapy for heteropathy" in traditional Chinese medicine (TCM), different diseases with the same clinical symptoms can be treated with the same medicines. Qingfei Dayuan granules (QFDY), a type of Chinese herbal preparation included in the TCM Diagnosis and Treatment Protocol for COVID-19 of Hubei Province issued by the Health Commission of Hubei Province in 2021, are recommended for patients suffering from COVID-19 with symptoms of fever, cough, and fatigue, among others. Additionally, recent studies have shown that QFDY effectively alleviates fever, cough, and other clinical symptoms in patients with influenza and URTIs. Materials and methods: The study was designed as a multicenter, randomized, double-blind, placebo-controlled clinical trial for treatment for influenza and URTIs manifested by pulmonary heat-toxin syndrome (PHTS) with QFDY. A total of 220 eligible patients were enrolled from eight first-class hospitals in five cities of Hubei Province in China and randomly assigned to receive either 15 g of QFDY or a placebo three times a day for 5 days. The primary outcome was the complete fever relief time. Secondary outcomes included efficacy evaluation of TCM syndromes, scores of TCM syndromes, cure rate of each single symptom, incidence of comorbidities and progression to severe conditions, combined medications, and laboratory tests. Safety evaluations mainly involved adverse events (AEs) and changes in vital signs during the study. Results: Compared with the placebo group, the complete fever relief time was shorter in the QFDY group, 24 h (12.0, 48.0) in the full analysis set (FAS) and 24 h (12.0, 49.5) in the per-protocol set (PPS) (p ≤ 0.001). After a 3-day treatment, the clinical recovery rate (22.3% in the FAS and 21.6% in the PPS) and cure rate of cough (38.6% in the FAS and 37.9% in the PPS), a stuffy and running nose, and sneezing (60.0% in the FAS and 59.5% in the PPS) in the QFDY group were higher than those in the placebo group (p < 0.05). The number of patients taking antibiotics for more than 24 h in the placebo group (nine cases) was significantly higher than that in the QFDY group (one case) (p < 0.05). There were no significant differences between the two groups in terms of scores of TCM syndromes, incidence of comorbidities or progression to severe conditions, combined use of acetaminophen tablets or phlegm-resolving medicines, and laboratory tests (p > 0.05). Meanwhile, no significant difference was found in the incidence of AEs and vital signs between the two groups (p > 0.05). Conclusion: The trial showed that QFDY was an effective and safe treatment modality for influenza and URTIs manifested by PHTS because it shortened the complete fever relief time, accelerated clinical recovery, and alleviated symptoms such as cough, a stuffy and running nose, and sneezing during the course of treatment. Clinical trial registration: https://www.chictr.org.cn/showproj.aspx?proj=131702, identifier ChiCTR2100049695.
RESUMO
Background: The role of leucine in sarcopenia prevention remains unclear. We aimed to summarize the published data from randomized controlled trials (RCTs) to estimate the effect of leucine supplementation on sarcopenia-related measures in older adults. Methods: A systematic literature search was performed using the electronic databases PubMed, Embase, and Web of Science with restriction to randomized controlled trials design from January 1, 2009 to March 19, 2022. Sarcopenia-related measures included handgrip strength, total lean mass, gait speed, leg press, 6-min walk test, short-physical performance battery, timed up-and-go test and 30-s chair-stand test. Fixed- and random-effects meta-analysis models were used to generate pooled weighted mean differences (WMDs) and 95% CIs. Heterogeneity was examined in subgroup and sensitivity analyses. Publication bias assessments were performed. Results: A total of 17 RCTs enrolling 1418 subjects were identified. Leucine-isolated supplementation showed no effect on total lean mass (WMD = 0.03 kg, 95% CI: -0.51, 0.57, P = 0.917), handgrip strength (WMD = 1.23 kg, 95% CI: -0.58, 3.03, P = 0.183) and leg press (WMD = -1.35 kg, 95% CI: -7.46, 4.77, P = 0.666). However, leucine-combined supplementation including vitamin D showed a significant improvement in handgrip strength (WMD = 2.17 kg, 95% CI: 0.24, 4.10, P = 0.027) and gait speed (WMD = 0.03 m/s, 95% CI: 0.01, 0.05, P = 0.008). Conclusion: Leucine-isolated supplementation did not improve muscle mass and strength in elderly. However, leucine-combined supplementation including vitamin D exhibited a significant benefit for muscle strength and performance including handgrip strength and gait speed in older adults. A combination of nutritional supplements would be a viable option for improving sarcopenia.
RESUMO
The area under the receiver operating characteristic curve (AUC) is widely used in evaluating diagnostic performance for many clinical tasks. It is still challenging to evaluate the reading performance of distinguishing between positive and negative regions of interest (ROIs) in the nested-data problem, where multiple ROIs are nested within the cases. To address this issue, we identify two kinds of AUC estimators, within-cases AUC and between-cases AUC. We focus on the between-cases AUC estimator, since our main research interest is in patient-level diagnostic performance rather than location-level performance (the ability to separate ROIs with and without disease within each patient). Another reason is that as the case number increases, the number of between-cases paired ROIs is much larger than the number of within-cases ROIs. We provide estimators for the variance of the between-cases AUC and for the covariance when there are two readers. We derive and prove the above estimators' theoretical values based on a simulation model and characterize their behavior using Monte Carlo simulation results. We also provide a real-data example. Moreover, we connect the distribution-based simulation model with the simulation model based on the linear mixed-effect model, which helps better understand the sources of variation in the simulated dataset.
Assuntos
Área Sob a Curva , Humanos , Curva ROC , Método de Monte Carlo , Simulação por Computador , Modelos LinearesRESUMO
The COVID-19 pandemic introduced risks and challenges to global food and nutrition security. In this paper, we examine the impact of the COVID-19 pandemic on the nutritional intake of China's rural residents using panel data and a fixed effects model. The data were collected in 2019 and 2020 and covered nine provinces and 2631 households in rural China. The results reveal that an increase of 100 confirmed cases in a county resulted in a 1.30% (p < 0.01), 1.42% (p < 0.01), 1.65% (p < 0.01), and 1.15% (p < 0.01) decrease in per capita intake of dietary energy, carbohydrates, fats, and proteins, respectively. Moreover, the COVID-19 pandemic had a significant and negative effect on dietary macronutrient intake in the low-income group at the 5% level of significance. Our study indicates that the potential insufficient nutrition situation, nutritional imbalance, and dietary imbalance of low-income rural residents should be addressed appropriately.