Objective To evaluate the characteristics of the mass balance and pharmacokinetics of[14 C]birociclib in Chinese male healthy volunteers after a single oral administration.Methods This study used a 14 C labeled method to investigate the mass balance and biological transformation of birociclib in human.Subjects were given a single oral dose of 360 mg/50 pCi of[14 C]birociclib suspension after meals.The blood,urine,and fecal samples were collected at specified time points/intervals after administration.The radiation levels of 14 C labeled birociclib-related compounds in the blood,plasma,urine,and feces were analyzed using liquid scintillation counting.In addition,a combination of high-performance liquid chromatography and on-line/off-line isotope detectors was used to obtain radioactive isotope metabolite spectra of plasma,urine,and fecal samples,and high-resolution mass spectrometry was used to identify the main metabolites.Results A total of 6 healthy male subjects were enrolled in this study.The median peak time of radioactive components in plasma was 5.00 h and the average terminal elimination half-life was 43.70 h after administration.The radioactive components were basically excreted and cleared from the body within 288.00 hours after administration,and average cumulative recovery rate of radioactive drugs was(94.10±8.19)％.The radioactive drugs were mainly excreted through feces,accounting for(84.60±7.10)％of the dose of radioactive drugs administered.Urine was the secondary excretory pathway,accounting for 9.41％of the dose of radioactive drugs administered.Metabolic analysis indicated that the prototype drug was the main radioactive components in plasma samples.The main metabolites in plasma were RM4(XZP-5286),RM6(XZP-3584),and RM7(XZP-5736).The drugs were mainly cleared from the body in the form of prototype drugs and metabolites.In addition to prototype drugs,a total of 9 metabolites were identified and analyzed in plasma,urine,and fecal samples,all of which were phase 1 metabolites.The main metabolic and clearance pathways of drugs in the body were deethylation,diisopropylat ion,oxidation,etc.Conclusion After a single oral administration of[14C]birociclib suspension to healthy subjects,it was mainly cleared from the body in the form of prototype drugs and metabolites,with feces as the main excretory pathway and urine as the secondary excretory pathway.Drugs mainly undergo metabolic reactions in the body,such as deethylation,diisopropylation,and oxidation.The subjects were well tolerance after administration.

Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.

Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.

Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.

Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.

Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.

The Hedgehog(Hh) signaling pathway has the functions of improving embryogenesis and maintaining tissue homeostasis. By influencing the tumor microenvironment, intervening in cell apoptosis, and regulating angiogenesis, it is pivotal in the occurrence, progression, and recovery of various tumors. Therefore, targeting and inhibiting the abnormal activation of the Hh pathway has become a potential research strategy for alleviating and treating cancer. Currently, traditional Chinese medicine(TCM) is highly favored for treating cancer and other challenging and severe diseases due to its advantages, such as minimal side effects, high efficacy, lack of dependency, and the ability to address both symptoms and underlying causes. This review aimed to provide a scientific foundation and research ideas for the prevention and treatment of cancer with TCM by summarizing and reviewing the correlation between the Hh pathway and tumors, as well as the feasibility of using TCM to modulate the Hh pathway for anti-tumor effects.
Hedgehog Proteins/genetics* ; Humans ; Signal Transduction/drug effects* ; Neoplasms/metabolism* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional

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).
Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19/epidemiology* ; COVID-19 Drug Treatment ; Aged ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/adverse effects* ; SARS-CoV-2 ; Treatment Outcome ; China/epidemiology* ; Adult

Humans ; DNA, Mitochondrial ; Cross-Sectional Studies ; East Asian People ; DNA Methylation ; Hypertension/epidemiology* ; China/epidemiology*

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.