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.

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

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.

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.

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.

Objective:The Qinzhi Zhudan formula(QZZD)exhibits a prominent therapeutic effect in the treatment of vascular dementia(VaD).This study combined a network pharmacology approach and experimental validation to identify the underlying biological mechanism of QZZD against VaD.Methods:Male Wistar rats received bilateral common carotid artery occlusion(BCCAO)surgery,and after 4 weeks of intragastric administration of QZZD,the therapeutic effect was assessed using the Morris water maze test and cerebral blood flow(CBF)assessment.Hematoxylin and eosin staining,Nissl staining,and electron microscopy were used to measure the histopathological changes in the neurons of rats.The effect of QZZD treatment on hippocampal neurotransmitters was assessed by high-performance liquid chromatography with electrochemical detection and liquid chromatography mass spectrometry.Immunofluorescence was used to observe VaD-induced microglia activation.The inflammatory cytokine levels were assessed by enzyme linked immunosorbent assay.Western blot was used to examine the TNFR1-mediated TNF pathway,which was screened out by network pharmacology analysis.Results:QZZD treatment alleviated pathological changes and neuronal damage in VaD rats and atten-uated their cognitive impairment.In addition,QZZD increased CBF and the expression of acetylcholine and 5-hydroxytryptamine in the hippocampal region.Notably,QZZD inhibited microglial activation and the expression of IL-6 and TNF-a.Network pharmacology and western blot indicated that QZZD inhibited the levels of TNFR1,NF-KBp65,p-ERK,TNF-α,and IL-6,which are related to the TNFR1-mediated TNF signaling pathway.Conclusion:QZZD clearly improved learning and memory function,reduced brain pathological damage,elevated CBF and hippocampal neurotransmitter levels,and alleviated neuroinflammation of VaD rats partly by inhibiting the TNFR1-mediated TNF pathway,indicating its potential value in the clinical therapy of VaD.

Aging/metabolism* ; Animals ; Gene Expression Regulation ; Macaca fascicularis ; Retina/metabolism* ; Single-Cell Analysis

Objective:To explore the effects of maternal pre-pregnancy body mass index (BMI) and gestational weight gain and its subtypes on the risk of preeclampsia.Methods:Pregnant women delivered in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Shanxi Medical University from March 2012 to September 2016 were selected as the research subjects. According to the inclusion and exclusion criteria, 9 274 pregnant women were included. 901 preeclampsia pregnant women were selected as the case group, and 8 373 non-preeclampsia pregnant women were selected as the control group. General demographic characteristics, pre-pregnancy weight, height, lifestyle during pregnancy, reproductive history, and disease history of pregnant women were collected, and pre-pregnancy BMI and gestational weight gain were calculated. Unconditional logistic regression was used to analyze the relationship between pre-pregnancy BMI and weight gain during pregnancy and PE and its clinical subtypes.Results:Among the 901 preeclampsia after inclusion and exclusion, 401 cases were diagnosed as early-onset PE (EOPE), 500 cases were late-onset PE (LOPE), 178 cases were Mild PE (MPE), and 723 cases were severe PE (SPE). There were statistically significant differences between PE and non-PE pregnant women in terms of maternal age, residence, parity, family history of gestational diabetes and hypertension ( P<0.05). After adjusting for the above factors, the logistic regression analysis results showed that pre-pregnancy BMI<18.5 kg/m 2 and inadequate gestational weight gain were protective factors for PE ( OR=0.74, 95% CI: 0.56-0.98; OR=0.78, 95% CI: 0.62-0.99), while pre-pregnancy BMI≥24.0 kg/m 2 and excessive gestational weight gain were risk factors for PE ( OR=1.82, 95% CI: 1.54-2.14; OR=1.82, 95% CI: 1.54-2.15). After subtype analysis on PE, the results showed that pre-pregnancy BMI<18.5 kg/m 2 was a protective factor for EOPE and MPE ( OR=0.52, 95% CI: 0.32-0.83; OR=0.47, 95% CI: 0.23-0.97), while pre-pregnancy BMI≥24.0 kg/m 2 and excessive gestational weight gain were risk factors for clinical subtypes of PE. After stratification according to pre-pregnancy BMI, excessive gestational weight gain was the risk factor for PE ( OR=1.86, 95% CI: 1.51-2.30; OR=1.90, 95% CI: 1.39-2.60) in pregnant women 18.5 kg/m 2≤BMI<24.0 kg/m 2 and ≥24.0 kg/m 2. Inadequate gestational weight gain ( OR=0.55, 95% CI: 0.34-0.89) was a protective factor for PE in pregnant women with pre-pregnancy BMI≥24.0 kg/m 2. Excessive gestational weight gain ( OR=4.05, 95% CI: 1.20-13.69) was a risk factor for EOPE in pregnant women with pre-pregnancy BMI<18.5 kg/m 2. Excessive gestational weight gain was a risk factor for the clinical subtype of PE in pregnant women 18.5 kg/m 2≤BMI<24.0 kg/m 2 before pregnancy. Inadequate gestational weight gain was a protective factor for EOPE and MPE ( OR=0.39, 95% CI: 0.19-0.80; OR=0.29, 95% CI: 0.11-0.77) in pregnant women with pre-pregnancy BMI≥24.0 kg/m 2. Excessive weight gain was a risk factor for EOPE, LOPE and SPE ( OR=1.60, 95% CI: 1.06-2.42; OR=2.20, 95% CI: 1.44-3.37; OR=2.28, 95% CI: 1.58-3.29). Conclusions:Pre-pregnancy BMI and gestational weight gain affect the risk of preeclampsia and its clinical subtypes. In contrast, the influence of gestational weight gain on preeclampsia varies among different pre-pregnancy BMI groups. Therefore, it is recommended to pay attention to the changes in pre-pregnancy BMI and gestational weight gain simultaneously to reduce preeclampsia.