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Purpose: CaoHuangGuiXiang (CHGX) formula is a traditional Chinese medicine for the treatment of Candida-related infection. However, its antifungal mechanisms against the emerging fungal pathogen Candida auris remain unclear. This study aimed to evaluate the antifungal activity of the dichloromethane extract of CHGX (CHGX-DME) and clarified its antifungal mechanims against C. auris. Methods: The major components of CHGX-DME were identified by ultra-performance liquid chromatography tandem mass spectrometry. Then, the minimal inhibitory concentration (MIC) assay and the time-kill kinetic assay were performed to investigate the in vitro antifungal activity of CHGX-DME against C. auris, including 8 isolates of 4 discrete clades and 2 special phenotypes (filamentous and aggregative). Furthermore, the effect of CHGX-DME on biofilm development was examined. In addition, the in vivo toxicity and efficacy of CHGX-DME were evaluated in a Galleria mellonella infection model. Results: First, 20 major compounds in CHGX-DME were detected and characterized. The MIC50% and MIC90% of CHGX-DME against C. auris isolates ranged from 50-200 mg/L and 100-400 mg/L, respectively. At 400 mg/L, CHGX-DME was able to efficiently kill more than 70% and 90% of C. auris cells after 3 hours and 6 hours of treatment, respectively. This notable antifungal activity exhibited a dosage- and time-dependent manner. Moreover, CHGX-DME not only played a critical role in inhibiting the proliferation of filamentous and aggregative cells, but also showed restricting effect on biofilm development in C. auris. Importantly, it significantly improved the survival rate and reduced the fungal burden in G. mellonella infection models, suggesting a remarkable treatment effect against C. auris infection. Conclusion: CHGX-DME exhibited potent antifungal activity against C. auris and significantly ameliorated this fungal infection in the G. mellonella model, confirming that it would be a promising antifungal drug for the troublesome and emerging fungal pathogen C. auris.
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Circulating tumor cells (CTC) are considered metastatic precursors that are shed from the primary or metastatic deposits and navigate the bloodstream before undergoing extravasation to establish distant metastases. Metabolic reprogramming appears to be a hallmark of metastatic progression, yet current methods for evaluating metabolic heterogeneity within organ-specific metastases in vivo are limited. To overcome this challenge, we present Biofluorescence Imaging-Guided Spatial Metabolic Tracing (BIGSMT), a novel approach integrating in vivo biofluorescence imaging, stable isotope tracing, stain-free laser capture microdissection, and liquid chromatography-mass spectrometry. This innovative technology obviates the need for staining or intricate sample preparation, mitigating metabolite loss, and substantially enhances detection sensitivity and accuracy through chemical derivatization of polar metabolites in central carbon pathways. Application of BIGSMT to a preclinical CTC-mediated metastasis mouse model revealed significant heterogeneity in the in vivo carbon flux from glucose into glycolysis and the tricarboxylic acid (TCA) cycle across distinct metastatic sites. Our analysis indicates that carbon predominantly enters the TCA cycle through the enzymatic reaction catalyzed by pyruvate dehydrogenase. Thus, our spatially resolved BIGSMT technology provides fresh insights into the metabolic heterogeneity and evolution during melanoma CTC-mediated metastatic progression and points to novel therapeutic opportunities.
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Purpose: This meta-analysis aims to identify whether patients with sepsis who have persistent tachycardia despite initial resuscitation can benefit from ultrashort-acting ß-blockers. Materials and methods: Relevant studies from MEDLINE, the Cochrane Library, and Embase were searched by two independent investigators. RevMan version 5.3 (Cochrane Collaboration) was used for statistical analysis. Results: A total of 10 studies were identified and incorporated into the meta-analysis. The results showed that the administration of ultrashort-acting ß-blockers (esmolol/landiolol) in patients with sepsis with persistent tachycardia despite initial resuscitation was significantly associated with a lower 28-day mortality rate (risk ratio [RR], 0.73; 95% confidence interval [CI], 0.57-0.93; and pË0.01). Subgroup analysis showed that the administration of esmolol in patients with sepsis was significantly associated with a lower 28-day mortality rate (RR, 0.68; 95% CI, 0.55-0.84; and pË0.001), while there was no significant difference between the landiolol and control groups (RR, 0.98; 95% CI, 0.41-2.34; and p = 0.96). No significant differences between the two groups were found in 90-day mortality, mean arterial pressure (MAP), lactate (Lac) level, cardiac index (CI), and troponin I (TnI) at 24 h after enrollment. Conclusion: The meta-analysis indicated that the use of esmolol in patients with persistent tachycardia, despite initial resuscitation, was linked to a notable reduction in 28-day mortality rates. Therefore, this study advocates for the consideration of esmolol in the treatment of sepsis in cases where tachycardia persists despite initial resuscitation.
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ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis-associated encephalopathy (SAE) is a common and serious complication during the acute phase of and after recovery from sepsis that seriously affects the quality of life of patients. Traditional Chinese medicine (TCM) has been widely used in modern medicine for neurological anomalies and has become a therapeutic tool for the treatment of SAE due to its multitargeting effects and low toxicity and side effects. AIMS OF THE STUDY: This review provides insights into the pathogenesis and treatments of SAE, focusing on the clinical and experimental impacts of TCM formulations and their single components. METHODS: Several known databases such as PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI), and others were extensively explored with keywords and phrases such as "sepsis-associated encephalopathy", "traditional Chinese medicine", "herbs", "SAE", "sepsis", "cerebral" or other relevant terms to obtain literature between 2018 and 2024. RESULTS: Extensive evidence indicated that TCM could decrease mortality and normalize neurological function in patients with sepsis; these effects might be associated with factors such as reduced oxidative stress and downregulated expression of inflammatory factors. CONCLUSIONS: TCM shows notable efficacy in treating SAE, warranting deeper mechanistic studies to optimize its clinical application.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Encefalopatia Associada a Sepse , Humanos , Encefalopatia Associada a Sepse/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Sepse/tratamento farmacológico , Sepse/complicaçõesRESUMO
BACKGROUND: The dysfunction of human vascular smooth cells (hVSMCs) is significantly connected to the development of intracranial aneurysms (IAs). By suppressing the activity of microRNAs (miRNAs), circular RNAs (circRNAs) participate in IA pathogenesis. Nevertheless, the role of hsa_circ_0008571 in IAs remains unclear. METHODS: circRNA sequencing was used to identify circRNAs from human IA tissues. To determine the function of circ_0008571, Transwell, wound healing, and cell proliferation assays were conducted. To identify the target of circ_0008571, the analyses of CircInteractome and TargetScan, as well as the luciferase assay were carried out. Furthermore, circ_0008571 knockdown and over-expression were performed to investigate its functions in IA development and the underlying molecular mechanisms. RESULTS: Both hsa_circ_0008571 and Integrin beta 8 (ITGB8) were downregulated, while miR-145-5p transcription was elevated in the aneurysm wall of IAs patients compared to superficial temporal artery tissues. In vitro, cell migration and growth were dramatically suppressed after hsa_circ_0008571 overexpression. Mechanistically, has_circ_0008571 could suppress miR-145-5p activity by direct sponging. Moreover, we found that ITGB8 expression and the activation of the TGF-ß-mediated signaling pathway were significantly enhanced. CONCLUSION: The hsa_circ_0008571-miR-145-5p-ITGB8 axis plays an essential role in IA progression.
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Proliferação de Células , Aneurisma Intracraniano , MicroRNAs , Músculo Liso Vascular , Miócitos de Músculo Liso , RNA Circular , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Aneurisma Intracraniano/genética , Aneurisma Intracraniano/patologia , Aneurisma Intracraniano/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Proliferação de Células/genética , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Movimento Celular/genética , Fenótipo , Masculino , Feminino , Pessoa de Meia-Idade , Células Cultivadas , Cadeias beta de IntegrinasRESUMO
A highly ortho-selective CAr-H olefination of tertiary anilines without a directing group was developed. This reaction tolerated various substituted arenes and olefin coupling partners, affording ortho-olefination products in moderate to good yields. Preliminary mechanistic studies showed that N-Ac-d-Ala, Ag2CO3, and BQ were the key factors for tuning the regioselectivity from para to ortho. Density functional theory was used to achieve a theoretical understanding of the ortho selectivity.
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BACKGROUND: This paper attempted to clarify the role and mechanism of vacuolar protein sorting-associated protein 72 homolog (VPS72) in the progression of prostate cancer (PCa). METHODS: Clinical information and gene expression profiles of patients with prostate cancer were obtained from The Cancer Genome Atlas (TCGA). VPS72 expression in PCa and the potential mechanism by which VPS72 affects PCa progression was investigated. Next, we performed COX regression analysis to identify the independent prognostic factors of PCa, and constructed a nomogram. The sensitivity of chemotherapeutic medications was anticipated using "pRRophetic". Subsequently, in vitro assays to validate the effect of VPS72 on PCa cell proliferation, migration and susceptibility to anti-androgen therapy. RESULTS: The expression of VPS72 was considerably higher in PCa tissues compared to normal tissues. Significant correlations were found between high VPS72 expression and a poor prognosis and adverse clinicopathological factors. The nomogram model constructed based on VPS72 expression has good predictive performance. According to GSEA, VPS72-related genes were enriched in the NF-kB pathways, cytokine-cytokine receptor interaction and chemokine signaling pathway in PCa. Although PCa with low VPS72 expression was more adaptable to chemotherapeutic medications, our in vitro experiment showed that VPS72 knockdown significantly decreased the PCa cell migration, proliferation, and resistance to anti-androgen therapy. CONCLUSIONS: In summary our findings suggests that VPS72 could play a crucial role in the malignant progression of PCa, and its expression level can be employed as a possible biomarker of PCa prognosis.
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Biomarcadores Tumorais , Proliferação de Células , Progressão da Doença , Neoplasias da Próstata , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Androgênios/farmacologia , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Nomogramas , Prognóstico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismoRESUMO
Bacteria can be utilized for cancer therapy owing to their preferential colonization at tumor sites. However, unmodified non-pathogenic bacteria carry potential risks due to their non-specific targeting effects, and their anti-tumor activity is limited when used as monotherapy. In this study, a biohybrid-engineered bacterial system comprising non-pathogenic MG1655 bacteria modified with CDH17 nanobodies on their surface and conjugated with photosensitizer croconium (CR) molecules is developed. The resultant biohybrid bacteria can efficiently home to CDH17-positive tumors, including gastric, pancreatic, and colorectal cancers, and significantly suppress tumor growth upon irradiation. More importantly, biohybrid bacteria-mediated photothermal therapy (PTT) induced abundant macrophage infiltration in a syngeneic murine colorectal model. Further, that the STING pathway is activated in tumor macrophages by the released bacterial nucleic acid after PTT is revealed, leading to the production of type I interferons. The addition of CD47 nanobody but not PD-1 antibody to the PTT regimen can eradicate the tumors and extend survival. This results indicate that bacteria endowed with tumor-specific selectivity and coupled with photothermal payloads can serve as an innovative strategy for low-immunogenicity cancers. This strategy can potentially reprogram the tumor microenvironment by inducing macrophage infiltration and enhancing the efficacy of immunotherapy targeting macrophages.
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Neoplasias Gastrointestinais , Anticorpos de Domínio Único , Animais , Camundongos , Anticorpos de Domínio Único/imunologia , Neoplasias Gastrointestinais/imunologia , Neoplasias Gastrointestinais/terapia , Modelos Animais de Doenças , Proteínas de Membrana/imunologia , Proteínas de Membrana/genética , Terapia Fototérmica/métodos , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , HumanosRESUMO
This manuscript presents a comprehensive investigation into the role of lactate metabolism-related genes as potential prognostic markers in skin cutaneous melanoma (SKCM). Bulk-transcriptome data from The Cancer Genome Atlas (TCGA) and GSE19234, GSE22153, and GSE65904 cohorts from GEO database were processed and harmonized to mitigate batch effects. Lactate metabolism scores were assigned to individual cells using the 'AUCell' package. Weighted Co-expression Network Analysis (WGCNA) was employed to identify gene modules correlated with lactate metabolism. Machine learning algorithms were applied to construct a prognostic model, and its performance was evaluated in multiple cohorts. Immune correlation, mutation analysis, and enrichment analysis were conducted to further characterize the prognostic model's biological implications. Finally, the function of key gene NDUFS7 was verified by cell experiments. Machine learning resulted in an optimal prognostic model, demonstrating significant prognostic value across various cohorts. In the different cohorts, the high-risk group showed a poor prognosis. Immune analysis indicated differences in immune cell infiltration and checkpoint gene expression between risk groups. Mutation analysis identified genes with high mutation loads in SKCM. Enrichment analysis unveiled enriched pathways and biological processes in high-risk SKCM patients. NDUFS7 was found to be a hub gene in the protein-protein interaction network. After the expression of NDUFS7 was reduced by siRNA knockdown, CCK-8, colony formation, transwell and wound healing tests showed that the activity, proliferation and migration of A375 and WM115 cell lines were significantly decreased. This study offers insights into the prognostic significance of lactate metabolism-related genes in SKCM.
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Ácido Láctico , Aprendizado de Máquina , Melanoma , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Melanoma/genética , Melanoma/metabolismo , Prognóstico , Ácido Láctico/metabolismo , Análise de Célula Única , Mutação , Transcriptoma , Melanoma Maligno Cutâneo , Linhagem Celular Tumoral , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genéticaRESUMO
Surgery and targeted therapy are of equal importance for colorectal cancer (CRC) treatment. However, complete CRC tumor resection remains challenging, and new targeted agents are also needed for efficient CRC treatment. Cadherin 17 (CDH17) is a membrane protein that is highly expressed in CRC and, therefore, is an ideal target for imaging-guided surgery and therapeutics. This study utilizes CDH17 nanobody (E8-Nb) with the near-infrared (NIR) fluorescent dye IRDye800CW to construct a NIR-II fluorescent probe, E8-Nb-IR800CW, and a Pseudomonas exotoxin (PE)-based immunotoxin, E8-Nb-PE38, to evaluate their performance for CRC imaging, imaging-guided precise tumor excision, and antitumor effects. Our results show that E8-Nb-IR800CW efficiently recognizes CDH17 in CRC cells and tumor tissues, produces high-quality NIR-II images for CRC tumors, and enables precise tumor removal guided by NIR-II imaging. Additionally, fluorescent imaging confirms the targeting ability and specificity of the immunotoxin toward CDH17-positive tumors, providing the direct visible evidence for immunotoxin therapy. E8-Nb-PE38 immunotoxin markedly delays the growth of CRC through the induction of apoptosis and immunogenic cell death (ICD) in multiple CRC tumor models. Furthermore, E8-Nb-PE38 combined with 5-FU exerts synergistically antitumor effects and extends survival. This study highlights CDH17 as a promising target for CRC imaging, imaging-guided surgery, and drug delivery. Nanobodies targeting CDH17 hold great potential to construct NIR-II fluorescent probes for surgery navigation, and PE-based toxins fused with CDH17 nanobodies represent a novel therapeutic strategy for CRC treatment. Further investigation is warranted to validate these findings for potential clinical translation.
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In the heterostructure of two-dimensional (2D) materials, many novel physics phenomena are strongly dependent on the Moiré superlattice. How to achieve the continuous manipulation of the Moiré superlattice in the same sample is very important to study the evolution of various physical properties. Here, in minimally twisted monolayer-multilayer graphene, we found that bubble-induced strain has a huge impact on the Moiré superlattice. By employing the AFM tip to dynamically and continuously move the nanobubble, we realized the modulation of the Moiré superlattice, like the evolution of regular triangular domains into long strip domain structures with single or double domain walls. We also achieved controllable modulation of the Moiré superlattice by moving multiple nanobubbles and establishing the coupling of nanobubbles. Our work presents a flexible method for continuous and controllable manipulation of Moiré superlattices, which will be widely used to study novel physical properties in 2D heterostructures.
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Some nanomaterials with intrinsic protease-like activity have the advantages of good stability, biosafety, low price, large-scale preparation and unique property of nanomaterials, which are promising alternatives for natural proteases in various applications. An especial term, "nanoprotease", has been coined to stress the intrinsic proteolytic property of these nanomaterials. As a new generation of artificial proteases, they have become a burgeoning field, attracting many researchers to design and synthesize high performance nanoproteases. In this review, we summarize recent progress on all types of nanoproteases with regard of their activity, mechanism and application and introduce a new and effective strategy for engineering high-performance nanoproteases. In addition, we discuss the challenges and opportunities of nanoprotease research in the future.
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Biotecnologia , Nanoestruturas , Peptídeo Hidrolases , Peptídeo Hidrolases/metabolismo , Peptídeo Hidrolases/química , Nanoestruturas/química , Engenharia de ProteínasRESUMO
A Fe-Co dual-metal co-doped N containing the carbon composite (FeCo-HNC) was prepared by adjusting the ratio of iron to cobalt as well as the pyrolysis temperature with the assistance of functionalized silica template. Fe1Co-HNC, which was formed with 1D carbon nanotubes and 2D carbon nanosheets including a rich mesoporous structure, exhibited outstanding oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalytic activities. The ORR half-wave potential is 0.86 V (vs. reversible hydrogen electrode, RHE), and the OER overpotential is 0.76 V at 10 mA cm-2 with the Fe1Co-HNC catalyst. It also displayed superior performance in zinc-air batteries. This method provides a promising strategy for the fabrication of efficient transition metal-based carbon catalysts.
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L-Ascorbic acid 2-phosphate magnesium (AP-Mg) salt is a Vitamin C derivative frequently used as a raw material in cell culture media for research purposes as well as for Good Manufacturing Practice (GMP)-manufacturing of cell and tissue advanced therapy medicinal products. A selective reversed-phase HPLC (RP-LC) method was developed and validated. Commercially available AP-Mg products from different suppliers were analyzed. Various new impurities were found using this newly developed RP-LC method. Using quantitative nuclear magnetic resonance spectroscopy, a mass balance of roughly 99.9% was obtained; the total numbers of impurities detected in both methods are also identical. The values of the relative ultraviolet (UV) response factors at λ = 210 nm of the impurities in this RP-LC method were discussed. When equaling the overall mean relative response factor of the impurities to 0.6 (estimated central value), the mass balance in the RP-LC method was nearly 100%. The structures of the new impurities are proposed as ethylation derivatives of open-ring AP-Mg products as well as phosphorylated derivatives of ascorbic acid.
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As an escalating public health issue, obesity and overweight conditions are predispositions to various diseases and are exacerbated by concurrent chronic inflammation. Nonetheless, extant antiobesity pharmaceuticals (quercetin, capsaicin, catecholamine, etc.) manifest constrained efficacy alongside systemic toxic effects. Effective therapeutic approaches that selectively target adipose tissue, thereby enhancing local energy expenditure, surmounting the limitations of prevailing antiobesity modalities are highly expected. In this context, we developed a temperature-sensitive hydrogel loaded with recombinant high-density lipoprotein (rHDL) to achieve targeted delivery of resveratrol, an adipose browning activator, to adipose tissue. rHDL exhibits self-regulation on fat cell metabolism and demonstrates natural targeting toward scavenger receptor class B type I (SR-BI), which is highly expressed by fat cells, thereby achieving a synergistic effect for the treatment of obesity. Additionally, the dispersion of rHDL@Res in temperature-sensitive hydrogels, coupled with the regulation of their degradation and drug release rate, facilitated sustainable drug release at local adipose tissues over an extended period. Following 24 days' treatment regimen, obese mice exhibited improved metabolic status, resulting in a reduction of 68.2% of their inguinal white adipose tissue (ingWAT). Specifically, rHDL@Res/gel facilitated the conversion of fatty acids to phospholipids (PA, PC), expediting fat mobilization, mitigating triglyceride accumulation, and therefore facilitating adipose tissue reduction. Furthermore, rHDL@Res/gel demonstrated efficacy in attenuating obesity-induced inflammation and fostering angiogenesis in ingWAT. Collectively, this engineered local fat reduction platform demonstrated heightened effectiveness and safety through simultaneously targeting adipocytes, promoting WAT browning, regulating lipid metabolism, and controlling inflammation, showing promise for adipose-targeted therapy.
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Tecido Adiposo , Lipoproteínas HDL , Animais , Camundongos , Lipoproteínas HDL/química , Lipoproteínas HDL/metabolismo , Tecido Adiposo/metabolismo , Proteínas Recombinantes , Resveratrol/farmacologia , Resveratrol/química , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Hidrogéis/química , Camundongos Endogâmicos C57BL , Humanos , Masculino , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/química , Sistemas de Liberação de Medicamentos , Receptores Depuradores Classe B/metabolismoRESUMO
Rapid and accurate identification of the intracellular pH is critical in the field of biomedicine. In this work, we effectively identified and quantified the intracellular pH and its distribution at the single-cell level using an image sensor based on an ordinary bright-field optical microscope that divided the cell staining images into their red (R) and blue (B) channels. The grayscale of the R and B channels was subjected to a ratiometric operation to generate ratiometric grayscale cell images of the microscope. A standard curve of pH against ratiometric grayscale curve was then obtained by incubating HeLa cells at pH 6.00-7.60 in a high concentration K+ ion buffer solution containing nigericin for obtaining certain intracellular pH values. A good correlation was evidenced between pH and the ratiometric grayscale of the R and B channels in the pH range of 6.00-7.60. Subsequently, the intracellular pH value of the A549 cells under the experimental conditions was measured to be 7.22 ± 0.01 by the method. Furthermore, the changes in the intracellular pH of HeLa cells stimulated with hydrogen peroxide were sensitively monitored, which demonstrated the applicability of the method. Due to its ease of use, the developed colorimetric microscopy pH detection and monitoring method provide prospects for pH-related single-cell studies.
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An in-depth understanding of structure-activity relationship between the phase constitution and solar-to-hydrogen (STH) conversion efficiency is conducive to guiding the optimization route of targeted photocatalyst candidates, further establishing advanced photocatalytic systems. Herein, based on the concept of phase engineering, we encompassed the crystalline phase of CdS and achieved precise regulation of phase proportion as well as phase boundary width in the phase junction for the first time. The above cooperative effect not only modifies energy band distribution for sufficient redox potentials, but also guarantees the reverse migration orientation of photogenerated carriers in phase junction, thereby endowing photocarriers with a prolonged lifetime. Compared to pure cubic or hexagonal phase (72.6 or 101.1 µmol h-1 g-1), this CdS system with optimized phase junction demonstrates an improved photocatalytic hydrogen evolution activity of 1.04 mmol h-1 g-1 and favorable stability without cocatalyst assistance, which mainly stems from an efficient protons reduction process interacting with long-lived photogenerated electrons. This research explores the mechanism behind phase regulation and its relationship with junction capability, providing a powerful strategy to manipulate crystal phase distribution and paving a feasible avenue for other phase-dependent photocatalysts towards rational design of heterostructures based on different phases in solar energy conversion field.
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Sheep body size can directly reflect the growth rates and fattening rates of sheep and is also an important index for measuring the growth performance of meat sheep. In this study, high-resolution resequencing data from four sheep breeds (Dorper sheep, Suffolk sheep, Ouessant sheep, and Shetland sheep) were analyzed. The nonsynonymous single nucleotide polymorphisms of three candidate genes (KIAA1217, SNTA1, and LTBP1) were also genotyped in 642 healthy Ujumqin sheep using MALDI-TOFMS and the genotyping results were associated with growth traits. The results showed that different genotypes of the KIAA1217 g.24429511T>C locus had significant effects on the chest circumferences of Ujumqin sheep. The SNTA1 g.62222626C>A locus had different effects on the chest depths, shoulder widths and rump widths of Ujumqin sheep. This study showed that these two sites can be used for marker-assisted selection, which will be beneficial for future precision molecular breeding.
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OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION: This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).