ObjectiveTo explore the association between metabolic score for visceral fat（METS-VF） and cardiometabolic multimorbidity（CMM） as well as cognitive function in the elderly population， revealing the role of METS-VF as an assessment tool in this population， and providing evidence and new perspectives for the early screening and intervention strategies of CMM and cognitive function. MethodsThis study is based on cross-sectional data from the Hubei memory and aging cohort study（HMACS）， which includes elderly individuals aged 60 and above. The METS-VF index was calculated and divided into quartiles（Q1-Q4）. CMM was assessed through a questionnaire， defining CMM as the coexistence of at least two of the following conditions： diabetes， heart disease， and stroke. Standardized cognitive tests were used to evaluate overall cognition， memory， language， executive function， and attention. Logistic and Linear regression analysis was performed to explore the association between METS-VF and the risk of CMM as well as cognitive function. A restricted cubic spline was used to test the dose-response relationship， and subgroup analysis was conducted to assess the variation of METS-VF in different populations. Additionally， multinomial unordered logistic regression was used to evaluate the performance of METS-VF in predicting CMM morbidity patterns. ResultsA total of 3 790 elderly participants aged 60 and above were included. After adjusting for confounding factors， compared with the lowest quartile（Q1）， the Q4 group of METS-VF was associated with a higher risk of CMM ［OR=3.00，95%CI （2.18， 4.16）］， and with lower scores in overall cognition ［b=-0.12， 95%CI （-0.21，-0.04）］， attention ［b=-0.14， 95%CI （-0.24，-0.05）］， and executive function ［b=-0.10， 95%CI （-0.20，-0.00）］. Dose-response analysis did not show a nonlinear relationship between METS-VF and either CMM or cognitive function （P for nonlinear > 0.05）. Subgroup analysis revealed that the male group with higher METS-VF had lower overall cognitive scores， while the female group showed lower executive function scores （P for interaction ＜ 0.05 for both）. Multinomial unordered logistic regression analysis indicated that the METS-VF index was associated with an increased risk of diabetes with coronary heart disease ［OR=2.62，95%CI （1.66， 4.15）］ or concomitant stroke ［OR=2.66，95%CI （1.73， 4.09）］， especially in the group with both diabetes and stroke and coronary heart disease， where the association between METS-VF and the risk was strongest. ConclusionsAn increased METS-VF is associated with a higher risk of CMM and lower scores in overall cognition， attention， and executive function in the elderly population. Diabetes may be a key driving factor in the multimorbidity model. The METS-VF index can serve as a dual-purpose tool for screening cardiovascular metabolic risks and assessing cognitive function.

Precise management of the activity dose is a core component of the(early mobilization,EM)plan for ICU patients.However,the lack of clinical practice guidelines related to EM dose of existing programs hinders the implementation and development of EM in ICU patients to some extent.Therefore,this review focuses on 4 aspects,covering the definition of activity dose,assessment tools,the current clinical implementation status,and implications for future nursing.The aim is to systematically review the assessment tools and intervention strategies for the activity dose of EM in ICU patients,providing a reference for optimization of EM programs.

Precise management of the activity dose is a core component of the(early mobilization,EM)plan for ICU patients.However,the lack of clinical practice guidelines related to EM dose of existing programs hinders the implementation and development of EM in ICU patients to some extent.Therefore,this review focuses on 4 aspects,covering the definition of activity dose,assessment tools,the current clinical implementation status,and implications for future nursing.The aim is to systematically review the assessment tools and intervention strategies for the activity dose of EM in ICU patients,providing a reference for optimization of EM programs.

Objective To investigate the diagnostic value of the T2WI gray scale ratio for Hashimoto's thyroiditis(HT).Methods The T2WI-iterative decomposition of water and fat with echo asymmetry and least square estimation(IDEAL)quantitation sequence water images of 22 HT cases were analyzed retrospectively.The gray scale ratio of the thyroid,sternocleidomastoid muscle,trachea cavity,and subcutaneous fat at the same layer were measured on the picture archiving and communication systems(PACS).The gray scale ratios of thyroid/sternocleidomastoid muscle(T/M),thyroid/trachea cavity(T/Tr),and thyroid/lipid(T/L)were calculated.The intraclass correlation coefficient(ICC)was used to evaluate the consistency among the measurements,and the optimal threshold for distinguishing HT from non-HT was determined via the receiver operating characteristic(ROC)curve.The Spearman correlation analysis was used to analyze the correlation between T/M,T/Tr,T/L ratios,and titers of thyroid peroxidase antibody(TPO-Ab)and thyroglobulin antibody(Tg-Ab),respectively.Results On the T2WI-IDEAL quantitation sequence water images,the(x)±s of T/M,T/Tr,T/L ratios for HT and non-HT were 2.17±0.47 and 1.62±0.21(t=14.90,P<0.001),9.40±3.24 and 4.87±2.93(t=11.42,P<0.001),1.66±0.32 and 1.21±0.31(t=7.51,P<0.001),respectively.The area under the curve(AUC)of T/M,T/Tr,and T/L ratios for diagnosing HT were 0.89,0.86,and 0.85,respectively;the optimal thresholds were 1.90,3.50,and 1.36,and the sensitivity and specificity were 72.7%and 100%,100%and 40.5%,95.5%and 29.7%,respectively.The T/M ratio had a moderate correlation with TPO-Ab(r=0.513,P<0.05),and T/Tr,T/L ratios had a mild correlation with TPO-Ab,respectively.Conclusion The T/M ratio in the T2WI gray scale ratio can quantitatively and objectively distinguish HT from non-HT to some extent and is correlated with TPO-Ab.It has extremely high specificity and holds promise as a non-invasive imaging method for the diagnosis of incidental HT.

Ziziphi spinosae semen mainly contains contents of saponins,flavonoids,alkaloids and aliphatic acids.Meanwhile,it has a variety of activities such as sedative-hypnotic,anti-anxiety,anti-depression,nerve protection,cardiovascular and cerebrovascular protection,liver protection,and antioxidant,which is widely used in medicine,food,health food and other fields.The chemical constituents,pharmacological action and clinical application of Ziziphi spinosae semen were systematically summarized in this paper by reviewing the literature,in order to provide theoretical guidance for the sustainable development of the resources and the rational use of Ziziphi spinosae semen.

Multidrug resistance (MDR) is the main factor of tumor recurrence and chemotherapy failure in clinical practice. Its mechanism is relatively complex, and one of the most thoroughly studied mechanism is the overexpression of P-glycoprotein (P-gp) on tumor cell membrane. Most of the chemotherapy drugs are p-gp substrates, and tumor cells will transport the chemotherapy drugs to the extracellular through p-gp mediated active transport, so that the concentration of effective drugs in the cell is reduced, resulting in drug resistance, leading to the decline of clinical efficacy. The reversal agent of P-gp can reduce the intracellular pumping of chemotherapeutic drugs by regulating the expression and transport activity of P-gp, and enhance the sensitivity of tumor cells to chemotherapeutic drugs, thus improving the therapeutic effect. In this paper, we will summarize the natural plant active ingredients that can reverse P-gp mediated MDR to provide reference for clinical and related studies.

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Humans ; Adult ; Invasive Pulmonary Aspergillosis ; Pneumonia, Viral/complications* ; Risk Factors ; Pulmonary Aspergillosis/complications*

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

Extracorporeal membrane oxygenation (ECMO), a kind of life support technology that can replace lung and heart function, is widely used in critical respiratory and circulatory exhaustion. Because of the serious diseases and the use of interventional catheters, patients receiving ECMO life support are often administrated with broad-spectrum antimicrobial agents, which increase the risk of fungal infection. Fungal infection during ECMO can increase mortality. How to effectively control fungal infection is a thorny problem faced by clinicians. During the treatment of ECMO, the patient's physiological status, ECMO oxygenation membrane, circulation pipeline and other factors may change the pharmacokinetic profiles of antifungal drugs, thereby affect the clinical efficacy of drugs. This artical reviews the pharmacokinetic characteristics of antifungal drugs during ECMO support, in order to provide references for clinical antifungal treatment.