BACKGROUND: The COVID-19 pandemic, ongoing for over 2 years with evolving viral strains, including the highly infectious Omicron variant, underscores the pivotal role of Traditional Chinese Medicine (TCM) in pandemic intervention. Qingfei Paidu Granules (QFPG) are incorporated into the national TCM diagnosis and treatment protocol. This study aims to assess the clinical effectiveness of QFPG combined with nonpharmacological interventions in asymptomatic novel coronavirus infection. MATERIALS AND METHODS: Using a full-group randomized controlled trial, asymptomatic individuals from 3 wards of Fangcang Hospital were randomly assigned to 3 groups, each comprising 150 cases: F1, the nonpharmacological treatment group, receiving only Five Elements Music Therapy and Gongfa Therapy; F2, the comprehensive treatment group, receiving QFPG treatment combined with Five Elements Music Therapy and Gongfa Therapy; and F3, the pharmacological treatment group, receiving only QFPG treatment. The treatment duration for each group was 6 days. Clinical efficacy and safety among different treatment groups were observed, including the conversion time of COVID-19 nucleic acid detection, duration of hospitalization, conversion rate from mild to moderate cases, and occurrence of adverse events. RESULTS: All 450 participants were included and completed the study. The conversion rates on the first day of treatment were 10.7%, 30%, and 11.3% for the F1, F2, and F3 groups, respectively. Compared to F1, both F2 and F3 showed shortened first conversion time and time to double negative results, with first conversion times of 1.92 days for F2 and 2.29 days for F3. Additionally, the time in F2 was shorter compared to F3. Hospitalization duration was shortened in both F2 and F3 compared to F1, with no statistically significant difference between F2 and F3. The conversion rate from mild to moderate cases was lower in both F2 and F3 compared to F1, but the difference between F2 and F3 was not significant. CONCLUSION: Combining QFPG with traditional Chinese nonpharmacological interventions effectively shortened the conversion time of COVID-19 nucleic acid detection and reduced the conversion rate from asymptomatic infection to mild/moderate cases. This treatment approach is worth promoting in the management of asymptomatic patients during pandemics. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2200059007.
COVID-19 , Drugs, Chinese Herbal , SARS-CoV-2 , Humans , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/administration & dosage , Male , Female , COVID-19/therapy , Middle Aged , Adult , Medicine, Chinese Traditional/methods , COVID-19 Drug Treatment , Treatment Outcome , Combined Modality Therapy , Asymptomatic Infections/therapy
Although single-atom Cu sites exhibit high efficiency in CO2 hydrogenation to methanol, they are prone to forming Cu nanoparticles due to reduction and aggregation under reaction conditions, especially at high temperatures. Herein, single-atom Cu sites stabilized by adjacent Na+ ions have been successfully constructed within a metal-organic framework (MOF)-based catalyst, namely MOF-808-NaCu. It is found that the electrostatic interaction between the Na+ and Hδ- species plays a pivotal role in upholding the atomic dispersion of Cu in MOF-808-NaCu during CO2 hydrogenation, even at temperatures of up to 275°C. This exceptional stabilization effect endows the catalyst with excellent activity (306 g·kgcat-1·h-1), high selectivity to methanol (93%) and long-term stability at elevated reaction temperatures, far surpassing the counterpart in the absence of Na+ (denoted as MOF-808-Cu). This work develops an effective strategy for the fabrication of stable single-atom sites for advanced catalysis by creating an alkali-decorated microenvironment in close proximity.
Satellite cells, the stem cells of skeletal muscle tissue, hold a remarkable regeneration capacity and therapeutic potential in regenerative medicine. However, low satellite cell yield from autologous or donor-derived muscles hinders the adoption of satellite cell transplantation for the treatment of muscle diseases, including Duchenne muscular dystrophy (DMD). To address this limitation, here we investigated whether satellite cells can be derived in allogeneic or xenogeneic animal hosts. First, injection of CRISPR/Cas9-corrected mouse DMD-induced pluripotent stem cells (iPSCs) into mouse blastocysts carrying an ablation system of host satellite cells gave rise to intraspecies chimeras exclusively carrying iPSC-derived satellite cells. Furthermore, injection of genetically corrected DMD-iPSCs into rat blastocysts resulted in the formation of interspecies rat-mouse chimeras harboring mouse satellite cells. Remarkably, iPSC-derived satellite cells or derivative myoblasts produced in intraspecies or interspecies chimeras restored dystrophin expression in DMD mice following intramuscular transplantation, and contributed to the satellite cell pool. Collectively, this study demonstrates the feasibility of producing therapeutically competent stem cells across divergent animal species, raising the possibility of generating human muscle stem cells in large animals for regenerative medicine purposes.
Objective: To evaluate the occurrence, development and outcome value of hyperfluorescent lymphocyte percentage (HFLC%) and immature granulocyte percentage (IG%) for acute pancreatitis (AP). Methods: The laboratory data collected from 1533 patients diagnosed with AP between August 2018 and August 2022 were retrospectively analyzed. The patients were classified into mild acute pancreatitis (MAP) and non-mild acute pancreatitis (Non-MAP) groups; non-MAP groups were additionally subgrouped based on HFLC% at day 7. White blood cells (WBC), HFLC%, and IG% were examined from day 1 (baseline) to day 14 post-admission using Sysmex XN Series Hematology Analyzers. C-reactive protein (CRP), serum amylase (AMY), and lipase (LPS) were detected by Beckman AU5800. Results: A total of 623 patients were finally included in the study [MAP group (n = 358) and Non-MAP group (n = 265)]. WBC, IG%, and CRP were higher in the Non-MAP group from day 1 to day 12 (all P<0.05). The HFLC% was not statistically significant from day 1 to day 6; yet, it increased on day 6 and 7 in the Non-MAP group. We divided patients in the Non-MAP group with complete data(101 patients) into HFLC% ≥ 2.9 %(31 patients) and HFLC% < 2.9 %(70 patients) according to the threshold of 7th day HFLC%. WBC, HFLC%, IG%, and CRP effectively predicted the progression of MAP to Non-MAP (all P < 0.001). HFLC% was the most obvious value, followed by CRP and IG%. Combined with HFLC%, IG%,CRP and WBC in day7, the ROC analysis showed that the area under ROC curve of the combined indicators was the largest (AUC = 0.912, P < 0.001) and had higher sensitivity and specificity than single-item assessment of AP outcomes(P < 0.05). HFLC% < 2.9 %, IG% > 1.7 %, CRP >28.66 mg/L, and WBC >9.24 × 109/L indicated the possibility of AP disease aggravation. Also, HFLC% <2.9 % was directly associated with infection, SIRS, APPACHII grade, and ICU admission (all P < 0.05). In non-MAP there was a significant negative correlation between HFLC% and APACHE-II score (rs = -0.312, P = 0.023). Conclusion: HFLC% <2.9 % on 7th day was directly indicated more infection, systemic inflammatory response syndrome(SIRS), higher APPACH II grade and ICU admission. HFLC% may be an independent laboratory marker for prognosis in AP. Combining HFLC% with IG%, CRP, and WBC helps evaluate AP patients' disease development and outcome.
Photocatalyst-coated optical fibers (P-OFs) using UV-A LEDs offer a highly promising solution for the degradation of micropollutants within municipal, reuse, industrial or home distribution systems, by integrating P-OFs into water storage tanks. P-OFs have photocatalysts attached to bundles of optical fibers, enabling their direct deployment within tanks. This eliminates the necessity for photocatalyst slurries, which would require additional membrane or separation systems. However, a current limitation of P-OFs is light management, specifically light oversaturation of the coated photocatalysts and short light transmission distances along fibers. This study overcomes this limitation and reveals strategies to improve the light dissipation uniformity along P-OFs, and demonstrates the performance of P-OFs on degrading a model micropollutant, carbamazepine (CBZ). Key tunable variables of fibers and light emission conditions, including photocatalyst coating patchiness (p), minimum light incident angles (θm), radiant flux launched to fibers (Φi), and fiber diameters (D), were modeled to establish their relationships with the light dissipation uniformity in TiO2-coated quartz optical fibers (TiO2-QOFs). We then validated modeling insights by conducting experiments to examine how these variables influence the generation of evanescent waves which are localized energy on fiber surfaces, leading to either photocatalyst activation or the recapture of unused light back into fibers. We observed substantial enhancements in evanescent waves generation by decreasing p and increasing θm, resulting in uniform light dissipation which reduces light oversaturation and improves light transmission distances. Moreover, these optimizations led to a remarkable three-fold improvement in CBZ degradation rates and a 65% reduction in energy consumption. Such improvement substantially reduces the capital and operational cost and enhances practicality of energy-efficient photocatalysis without additional chemical oxidants for micropollutant degradation in water storage tanks.
G-triplexes are G-rich oligonucleotides composed of three G-tracts and have absorbed much attention due to their potential biological functions and attractive performance in biosensing. Through the optimization of loop compositions, DNA lengths, and 5'-flanking bases of G-rich sequences, a new stable G-triplex sequence with 14 bases (G3-F15) was discovered to dramatically activate the fluorescence of Thioflavin T (ThT), a water-soluble fluorogenic dye. The fluorescence enhancement of ThT after binding with G3-F15 reached 3200 times, which was the strongest one by far among all of the G-rich sequences. The conformations of G3-F15 and G3-F15/ThT were studied by circular dichroism. The thermal stability measurements indicated that G3-F15 was a highly stable G-triplex structure. The conformations of G3-F15 and G3-F15/ThT in the presence of different metal cations were studied thoroughly by fluorescent spectroscopy, circular dichroism, and nuclear magnetic resonance. Furthermore, using the G3-F15/ThT complex as a fluorescent probe, a robust and simple turn-on fluorescent sensor for uracil-DNA glycosylase activity was developed. This study proposes a new systematic strategy to explore new functional G-rich sequences and their ligands, which will promote their applications in diagnosis, therapy, and biosensing.
Postpartum blood calcium (Ca) concentration is related to the reproduction and health of cattle. Oral calcium supplements were given to dairy cows after calving to increase blood Ca concentration and reduce the risk of hypocalcemia. However, studies have shown that oral Ca has different effects in preventing disease. The purposes of this study were (i) to conduct a meta-analysis to evaluate the expected effect of oral Ca on incidence of calving-related diseases, pregnancy risk and milk yield in dairy cows, and (ii) to make a quality assessment of these related studies. In total, 22 eligible studies were included in this review. Meta-analysis showed that oral Ca could significantly reduce the incidence of hypocalcemia (clinical hypocalcemia: relative risk (RR) = 0.67, 95% confidence interval (CI) = [0.52, 0.87]; subclinical hypocalcemia: RR = 0.81, CI = [0.72, 0.91]), and incidence of retained placenta (RR = 0.77, CI = [0.62, 0.95]), improved blood Ca concentrations: mean difference (MD) = 0.08; 95% CI = [0.04, 0.11]. For other results, the meta-analysis revealed a lack of evidence of the correlation between oral Ca and serum magnesium (Mg) / phosphorus (P) concentration (Mg: MD = -0.04; 95% CI = [-0.10, 0.02]; P: MD = 0.05; 95% CI = [-0.10, 0.21]) or incidence of other calving-related disorders (metritis: RR = 1.06, CI = [0.94, 1.19]; ketosis: RR = 1.04, CI = [0.91, 1.18]; mastitis: RR = 1.02, CI = [0.86, 1.21]; displacement of the abomasum: RR = 0.81, CI = [0.57, 1.16]) or pregnancy risk (pregnancy risk at first service: RR = 0.99, CI = [0.94, 1.05]; overall pregnancy rate: RR = 1.03, CI = [0.98, 1.08]) or milk yield (MD = 0.44; 95% CI = [-0.24, 1.13]). The distribution of the funnel plot formed by the included studies was symmetrical, and the Egger's test had a p > 0.05, indicating that there was no significant publication bias. Sensitivity analyses results suggested that the results of meta-analysis are robust. Quality assessment of the included studies revealed that the risk of bias was focused on selection bias, performance bias, detection bias and other sources of bias, and the future research should focus on these aspects.
Long-term manned spaceflight and extraterrestrial planet settlement become the focus of space powers. However, the potential influence of closed and socially isolating spaceflight on the brain function remains unclear. A 180-day controlled ecological life support system integrated experiment was conducted, establishing a spaceflight analog environment to explore the effect of long-term socially isolating living. Three crewmembers were enrolled and underwent resting-state fMRI scanning before and after the experiment. We performed both seed-based and network-based analyses to investigate the functional connectivity (FC) changes of the default mode network (DMN), considering its key role in multiple higher-order cognitive functions. Compared with normal controls, the leader of crewmembers exhibited significantly reduced within-DMN and between-DMN FC after the experiment, while two others exhibited opposite trends. Moreover, individual differences of FC changes were further supported by evidence from behavioral analyses. The findings may shed new light on the development of psychological protection for space exploration.
Background: Electrical impedance tomography (EIT) is a relatively recent functional imaging technique that is both noninvasive and radiation free. EIT measures the associated voltage when a weak current is applied to the surface of the human body to determine the distribution of electrical resistance within tissues. We performed a bibliometrics-based review to explore the geographic hotspots of current research and future trends developing in the field of EIT for mechanical ventilation. Methods: The Web of Science database was searched from its inception to June 25, 2023. CiteSpace software was used to visualize and analyze the relevant literature and identify the most impactful literature, trends, and hotspots. Results: 363 articles describing EIT use in mechanical ventilation were identified. A fluctuating growth in the number of publications was observed from 1998 to 2023. Germany had the highest number of articles (n=154), followed by Italy (n=53) and China (n=52). A cluster analysis of keyword co-occurrence revealed that "titration", "ventilator-related lung injury", and "oxygenation" were the most actively researched terms associated with the use of EIT in mechanically ventilated patients. Conclusions: Significant progress has been made in EIT research for mechanical ventilation. EIT research is limited to a small number of countries with a present research focus on the prevention and treatment of ventilator-related lung injury, oxygenation status, and prone ventilation. These topics are expected to remain research hotspots in the future.
OBJECTIVE: To summarize the clinical characteristics, therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma (HL). METHODS: A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled, and their clinical data, including sex, age, pathological type, Ann Arbor stage, ECOG score, blood test, ß2-microglobulin, lactate dehydrogenase level, albumin level were collected. The clinical characteristics, therapeutic effect and long-term prognosis of the patients were summarized and analyzed. RESULTS: In classical HL, nodular sclerosis HL accounted for the highest proportion of 51.6%, followed by mixed cellularity HL (36.5%), lymphocyte-rich classical HL (3.2%), and lymphocyte depletion HL (0.7%), while nodular lymphocyte predominant HL accounted for 4.8%. The 3-year overall survival (OS) rate of HL patients was 89.8%, and 5-year OS was 85.0%. The 3-year progression-free survival (PFS) rate was 73.4%, and 5-year PFS was 63.1%. Multivariate regression analysis indicated that IPI score was an independent negative factor, while hemoglobin (Hb) level was an independent positive factor for OS in HL patients. When the mediastinal mass size was 9.2 cm, it was most significant to judge the survival status of HL patients. 5-year OS and 5-year PFS were 97.4% and 76.0% in early-stage HL patients without large mass, respectively, while in patients with advanced-stage HL was 83.4% and 55.9% (both P < 0.05). After 2-4 courses of treatment, the overall response rate (ORR) of patients who received chemotherapy combined with radiotherapy was 95.0%, while that was 89.6% in those with chemotherapy alone. CONCLUSIONS: The overall prognosis of patients with HL is satisfactory, especially those in early-stage without large mass. IPI score and Hb level are independent risk factors for the prognosis of HL patients. A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.
Hodgkin Disease , Humans , Hodgkin Disease/therapy , Adult , Male , Prognosis , Female , Survival Rate , Young Adult
Candida auris, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in in vivo-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of C. auris using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in ERG11 and A585S in TAC1b, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in TAC1b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the SNG1 gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of C. auris and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. Further monitoring and validation efforts are crucial for a comprehensive understanding of the mechanisms of drug resistance in C. auris.
Antifungal Agents , Candidiasis , Humans , Antifungal Agents/pharmacology , Candidiasis/microbiology , Candida auris , Candida , Amphotericin B/pharmacology , Drug Resistance, Fungal/genetics , Microbial Sensitivity Tests
CRISPR/Cas9 gene editing technology, as a highly efficient genome editing method, has been extensively employed in the realm of animal husbandry for genetic improvement. With its remarkable efficiency and precision, this technology has revolutionized the field of animal husbandry. Currently, CRISPR/Cas9-based gene knockout, gene knock-in and gene modification techniques are widely employed to achieve precise enhancements in crucial production traits of livestock and poultry species. In this review, we summarize the operational principle and development history of CRISPR/Cas9 technology. Additionally, we highlight the research advancements utilizing this technology in muscle growth and development, fiber growth, milk quality composition, disease resistance breeding, and animal welfare within the livestock and poultry sectors. Our aim is to provide a more comprehensive understanding of the application of CRISPR/Cas9 technology in gene editing for livestock and poultry.
CRISPR-Cas Systems , Livestock , Animals , Livestock/genetics , Poultry/genetics , Gene Editing/methods , Gene Knock-In Techniques
AIMS: In order to explore new consumer demands for Chinese tea set products, propose an innovative tea set product design and evaluation method to improve the user experience and satisfaction of the produced tea sets, thereby promoting the development of the tea set market and the promotion of tea culture. METHODS: Firstly, grounded theory (GT) was used to analyze interview data to extract consumer demand indicators and construct a design evaluation hierarchical model. Secondly, the Analytical Hierarchy Process (AHP) was used to calculate the weights of the indicators, determine their priority of importance, and obtain several indicators that have a greater impact on the tea set design to guide innovative design practice. Lastly, the tea set design schemes were evaluated using the fuzzy comprehensive evaluation method to select the optimal design scheme and also to act as a guideline for further design optimization. CONCLUSION: This study explores the innovative design and evaluation method for tea set products based on GT-AHP-FCE and validates the feasibility of this approach through a practical example of tea set design inspired by "The Classic of Mountains and Seas.". It provides innovative theoretical and practical guidance for designers of subsequent tea set products and also provides a new path for the inheritance and innovation of traditional culture.
Analytic Hierarchy Process , Tea , Grounded Theory
BACKGROUND: As a well-known fact to the public, gestational diabetes mellitus (GDM) could bring serious risks for both pregnant women and infants. During this important investigation into the linkage between GDM patients and their altered expression in the serum, proteomics techniques were deployed to detect the differentially expressed proteins (DEPs) of in the serum of GDM patients to further explore its pathogenesis, and find out possible biomarkers to forecast GDM occurrence. AIM: To investigation serum proteins differentially expressed in GDM were assessed using isobaric tag for relative and absolute quantitation (iTRAQ) proteomics and bioinformatics analyses. METHODS: Subjects were divided into GDM and normal control groups according to the IADPSG diagnostic criteria. Serum samples were randomly selected from four cases in each group at 24-28 wk of gestation, and the blood samples were identified by applying iTRAQ technology combined with liquid chromatography-tandem mass spectrometry. Key proteins and signaling pathways associated with GDM were identified by bioinformatics analysis, and the expression of key proteins in serum from 12 wk to 16 wk of gestation was further verified using enzyme-linked immunosorbent assay (ELISA). RESULTS: Forty-seven proteins were significantly differentially expressed by analyzing the serum samples between the GDM gravidas as well as the healthy ones. Among them, 31 proteins were found to be upregulated notably and the rest 16 proteins were downregulated remarkably. Bioinformatic data report revealed abnormal expression of proteins associated with lipid metabolism, coagulation cascade activation, complement system and inflammatory response in the GDM group. ELISA results showed that the contents of RBP4, as well as ANGPTL8, increased in the serum of GDM gravidas compared with the healthy ones, and this change was found to initiate from 12 wk to 16 wk of gestation. CONCLUSION: GDM symptoms may involve abnormalities in lipid metabolism, coagulation cascade activation, complement system and inflammatory response. RBP4 and ANGPTL8 are expected to be early predictors of GDM.
BACKGROUND: Evidence of modifying effect of various dietary patterns (DPs) on risk of type 2 diabetes (T2D) induced by long-term exposure to air pollution (AP) is still rather lacking, which therefore we aimed to explore in this study. METHODS: We included 78,230 UK Biobank participants aged 40-70 years with at least 2 typical 24-hour dietary assessments and without baseline diabetes. The annual average concentration of particulate matter with diameter micrometers ≤2.5 (PM2.5) and ≤10 (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOX) estimated by land use regression model was the alternative proxy of long-term AP exposure. Three well-known prior DPs such as Mediterranean diet (MED), dietary approaches to stop hypertension diet (DASH), and empirical dietary inflammatory pattern (EDIP), as well as three posterior DPs derived by the rank reduced regression model were used to capture participants' dietary habits. Cox regression models were used to estimate AP-T2D and DP-T2D associations. Modifying effect of DPs on AP-T2D association was assessed using stratified analysis and heterogeneity test. RESULTS: During a median follow-up 12.19 years, 1,693 participants developed T2D. PM2.5, PM10, NO2, and NOX significantly increased the T2D risk (P <0.05), with hazard ratio (HR) and 95% confidence interval (95% CI) for per interquartile range increase being 1.09 (1.02,1.15), 1.04 (1.00, 1.09), 1.11 (1.04, 1.18), and 1.08 (1.03, 1.14), respectively. Comparing high with low adherence, healthy DPs were associated with a 14-41% lower T2D risk. Participants with high adherence to MED, DASH, and anti-EDIP, alongside the posterior anti-oxidative dietary pattern (AODP) had attenuated and statistically non-significant NO2-T2D and NOX-T2D associations (Pmodify <0.05). CONCLUSIONS: Multiple forms of healthy DPs help reduce the T2D risk associated with long-term exposure to NO2 and NOX. Our findings indicate that adherence to healthy DPs is a feasible T2D prevention strategy for people long-term suffering from NO2 and NOX pollution.
Air Pollutants , Air Pollution , Diabetes Mellitus, Type 2 , Humans , Cohort Studies , Air Pollutants/analysis , Nitrogen Dioxide/analysis , UK Biobank , Diabetes Mellitus, Type 2/epidemiology , Dietary Patterns , Biological Specimen Banks , Environmental Exposure/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Particulate Matter/analysis
PURPOSE: The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery. PATIENTS AND METHODS: OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population. RESULTS: Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]). CONCLUSION: NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.
Recent advancements in membrane-assisted seawater electrolysis powered by renewable energy offer a sustainable path to green hydrogen production. However, its large-scale implementation faces challenges due to slow power-to-hydrogen (P2H) conversion rates. Here we report a modular forward osmosis-water splitting (FOWS) system that integrates a thin-film composite FO membrane for water extraction with alkaline water electrolysis (AWE), denoted as FOWSAWE. This system generates high-purity hydrogen directly from wastewater at a rate of 448 Nm3 day-1 m-2 of membrane area, over 14 times faster than the state-of-the-art practice, with specific energy consumption as low as 3.96 kWh Nm-3. The rapid hydrogen production rate results from the utilisation of 1 M potassium hydroxide as a draw solution to extract water from wastewater, and as the electrolyte of AWE to split water and produce hydrogen. The current system enables this through the use of a potassium hydroxide-tolerant and hydrophilic FO membrane. The established water-hydrogen balance model can be applied to design modular FO and AWE units to meet demands at various scales, from households to cities, and from different water sources. The FOWSAWE system is a sustainable and an economical approach for producing hydrogen at a record-high rate directly from wastewater, marking a significant leap in P2H practice.
Cardiac hypertrophy is one of the key processes in the development of heart failure. Notably, small GTPases and GTPaseactivating proteins (GAPs) serve essential roles in cardiac hypertrophy. RhoGAP interacting with CIP4 homologs protein 1 (RICH1) is a RhoGAP that can regulate Cdc42/Rac1 and Factin dynamics. RICH1 is involved in cell proliferation and adhesion; however, to the best of our knowledge, its role in cardiac hypertrophy remains unknown. In the present study, the role of RICH1 in cardiomyocyte hypertrophy was assessed. Cell viability was analyzed using the Cell Counting Kit8 assay and cells surface area (CSA) was determined by cell fluorescence staining. Reverse transcriptionquantitative PCR and western blotting were used to assess the mRNA expression levels of hypertrophic marker genes, such as Nppa, Nppb and Myh7, and the protein expression levels of RICH1, respectively. RICH1 was shown to be downregulated in isoproterenol (ISO) or angiotensin II (Ang II)treated H9c2 cells. Notably, overexpression of RICH1 attenuated the upregulation of hypertrophyrelated markers, such as Nppa, Nppb and Myh7, and the enlargement of CSA induced by ISO and Ang II. By contrast, the knockdown of RICH1 exacerbated these effects. These findings suggested that RICH1 may be a novel suppressor of ISO or Ang IIinduced cardiomyocyte hypertrophy. The results of the present study will be beneficial to further studies assessing the role of RICH1 and its downstream molecules in inhibiting cardiac hypertrophy.
Heart Defects, Congenital , Myocytes, Cardiac , Nitrobenzoates , Procainamide/analogs & derivatives , Humans , Myocytes, Cardiac/metabolism , Angiotensin II/pharmacology , Angiotensin II/metabolism , Isoproterenol/pharmacology , Isoproterenol/metabolism , Cardiomegaly/chemically induced , Cardiomegaly/genetics , Cardiomegaly/metabolism , Heart Defects, Congenital/metabolism
Hyalectan cleavage may play an important role in extracellular matrix remodeling. However, the proteolytic enzyme responsible for hyalectan degradation for fetal membrane rupture at parturition remains unknown. Here, we reveal that versican (VCAN) is the major hyalectan in the amnion, where its cleavage increases at parturition with spontaneous rupture of membrane. We further reveal that ADAMTS4 is a crucial proteolytic enzyme for VCAN cleavage in the amnion. Inflammatory factors may enhance VCAN cleavage by inducing ADAMTS4 expression and inhibiting ADAMTS4 endocytosis in amnion fibroblasts. In turn, versikine, the VCAN cleavage product, induces inflammatory factors in amnion fibroblasts, thereby forming a feedforward loop between inflammation and VCAN degradation. Mouse studies show that intra-amniotic injection of ADAMTS4 induces preterm birth along with increased VCAN degradation and proinflammatory factors abundance in the fetal membranes. Conclusively, there is enhanced VCAN cleavage by ADAMTS4 in the amnion at parturition, which can be reenforced by inflammation.
ADAMTS4 Protein , Amnion , Versicans , Female , Humans , Infant, Newborn , Pregnancy , ADAMTS4 Protein/metabolism , Amnion/metabolism , Inflammation/metabolism , Parturition/metabolism , Peptide Hydrolases/metabolism , Premature Birth/metabolism , Versicans/metabolism , Animals , Mice
BACKGROUND: Letrozole has been proven to be an effective method for inducing ovulation. However, little attention has been paid to whether the lead follicle size will affect the success rate of intrauterine insemination (IUI) with ovulation induction with alone letrozole. Therefore, we hope to investigate the effect of dominant follicle size on pregnancy outcomes on human chorionic gonadotropin (hCG) day of the first letrozole-IUI. METHODS: A retrospective cohort study design was employed. We included patients with anovulation or unexplained infertility undergoing first IUI treatment with letrozole for ovarian stimulation. According to the dominant follicle size measured on the day of hCG trigger, patients were divided into six groups (≤ 18 mm, 18.1-19.0 mm, 19.1-20.0 mm, 20.1-21.0 mm, 21.1-22.0 mm, > 22 mm). Logistic models were used for estimating the odds ratios (ORs) with their 95% confidence interval (CIs) for achieving a clinical pregnancy or a live birth. A restricted cubic spline was drawn to explore the nonlinear relationship between follicle size and IUI outcomes. RESULTS: A total of 763 patients underwent first letrozole-IUI cycles in our study. Fisher exact test showed significant differences among the six follicle-size groups in the rates of pregnancy, clinical pregnancy and live birth (P < 0.05 in each group). After adjusting the potential confounding factors, compared with the follicles ≤ 18 mm in diameter group, 19.1-20.0 mm, 20.1-21.0 mm groups were 2.3 or 2.56 times more likely to get live birth [adjusted OR = 2.34, 95%CI (1.25-4.39); adjusted OR = 2.56, 95% CI (1.30-5.06)]. A restricted cubic spline showed an inverted U-shaped relationship between the size of dominant follicles and pregnancy rate, clinical pregnancy rate, and live birth rate, and the optimal follicle size range on the day of hCG trigger was 19.1-21.0 mm. When the E2 level on the day of hCG trigger was low than 200 pg/mL, the clinical pregnancy rates of 19.1-20.0 mm, 20.1-21.0 mm groups were still the highest. CONCLUSIONS: The optimal dominant follicle size was between 19.1 and 21.0 mm in hCG-triggered letrozole-IUI cycles. Either too large or too small follicles may lead to a decrease in pregnancy rate. Using follicle size as a predicator of pregnancy outcomes is more meaningful when estrogen on the day of hCG trigger is less than 200 pg/ml.
Insemination, Artificial , Pregnancy Outcome , Pregnancy , Female , Humans , Letrozole , Retrospective Studies , Insemination, Artificial/methods , Pregnancy Rate
