Based on the pharmacokinetics theory, this study investigated the pharmacokinetic characteristics of albiflorin, paeoniflorin, wogonoside, and wogonin in normal and febrile rats and summarized absorption and elimination rules of Dayuanyin in them to provide reference for further development and clinical application of Dayuanyin. Blood samples were taken from the fundus venous plexus of normal and model rats after intragastric administration of Dayuanyin at different time points. The concentration of each substance in blood was determined by ultra performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS) technique at different time points. DAS 2.0, a piece of pharmacokinetics software, was used to calculate the pharmacokinetic parameters of each component. The results show that the 4 components had good linear relationship in their respective ranges, and the results of methodological investigation met the requirements. The pharmacokinetic parameters of C_(max), T_(max), t_(1/2), AUC_(0-t), AUC_(0-∞), and MRT_(0-t) were calculated by the DAS 2.0 non-compartmental model. Compared with those in the normal group, C_(max) and AUC_(0-t) of the 4 components in the model group were significantly increased. There were significant differences in the pharmacokinetic characteristics between the normal and model groups, suggesting that the absorption and elimination of Dayuanyin may be affected by the changes of internal environment of the body in different physiological states.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Fever/metabolism* ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Glucosides/pharmacokinetics* ; Monoterpenes

Based on the ultra performance liquid chromatography-quadrupole Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology, combined with related literature, databases, and reference material information, this study qualitatively analyzed the components of Dayuanyin in the tissue of rats after gavage and employed molecular docking technology to predict the rationality of the mechanism behind the antipyretic effect of the in vivo components in Dayuanyin. A total of 21, 26, 20, 21, 14, and 31 prototype components and 3, 16, 3, 7, 5, and 24 metabolites were identified from the heart, liver, spleen, lung, kidney, and hypothalamus of the rats, respectively, and the binding ability of key components and targets was further verified by molecular docking. The results showed that all components had good binding ability with targets. The established UPLC-Q-Exactive Orbitrap-MS could effectively and quickly identify the Dayuanyin components distributed in tissue and preliminarily identify their metabolites. Many components were identified in the hypothalamus, which suggested that the components delivered to the brain should be focused on in the study on Dayuanyin in the treatment of febrile diseases. The molecular docking technology was used to predict the rationality of the mechanism behind its antipyretic effect, which lays the foundation for the clarification of the material basis and action mechanism of Dayuanyin, the development of new preparations, and the prediction of quality markers.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Molecular Docking Simulation ; Male ; Antipyretics/metabolism* ; Rats, Sprague-Dawley ; Tissue Distribution ; Mass Spectrometry ; Chromatography, High Pressure Liquid ; Hypothalamus/metabolism*

Objective To investigate the distribution patterns of traditional Chinese medicine(TCM)constitution in 959 patients with endometriosis(EMs).Methods From January 2019 to November 2019,959 EMs patients were selected from Guang'anmen Hospital of China Academy of Chinese Medical Sciences,Beijing Obstetrics and Gynecology Hospital Affiliated to Capital Medical University,Beijing Hospital,Dongfang Hospital of Beijing University of Chinese Medicine,Beijing Friendship Hospital Affiliated to Capital Medical University,and Fuxing Hospital Affiliated to Capital Medical University.The general clinical information of the patients was recorded and then the TCM constitution was identified.After that,the correlation of TCM constitution distribution with concurrent constitution and the relationship of TCM constitution distribution with age and the complication of dysmenorrhea were analyzed.Results(1)The constitution types of EMs patients listed in descending order of the proportion were yang deficiency constitution(65.1％,624/959),qi stagnation constitution(58.4％,560/959),qi deficiency constitution(52.8％,506/959),blood stasis constitution(44.2％,424/959),phlegm-damp constitution(42.5％,408/959),damp-heat constitution(41.9％,402/959),yin deficiency constitution(39.6％,380/959),balanced constitution(26.8％,257/959),and inherited special constitution(16.6％,159/959).Among the patients,there were fewer patients with single constitution,accounting for 20.2％(194/959),and most of them had concurrent constitution types,accounting for 79.8％(765/959).(2)The association rule mining based on Apriori algorithm obtained 33 related rules.The concurrent constitution types of qi deficiency-yang deficiency,blood stasis-yang deficiency,and blood stasis-qi stagnation were the association rules with high confidence.(3)Compared with patients aged 35 years and below,the patients over 35 years old were predominated by high proportion of blood stasis constitution(P＜0.05).Compared with patients without dysmenorrhea,the patients with dysmenorrhea had the increased proportion of biased constitutions and the decreased proportion of balanced constitution(P＜0.05 or P＜0.01).Conclusion Yang deficiency constitution,qi stagnation constitution,qi deficiency constitution and blood stasis constitution are the high-risk constitution types of EMs patients.The concurrent constitution types are commonly seen in EMs patients,which are more common than single biased constitution.Management of EMs patients with the methods of warming yang,relieving stagnation,benefiting qi and activating blood will be helpful for correcting the biased constitutions in time and preventing disease progression,which will achieve the preventive treatment efficacy through TCM constitution correction.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,neomangiferin,catechin,caffeic acid,mangiferin,isomangiferin,albiflorin,paeoniflorin,vitexin,liquiritin,scutellarin,baicalin,liquiritigenin,timosaponin BⅡ,quercetin,wogonoside,benzoylpaeoniflorin,isoliquiritigenin,honokiol,magnolol,norarecaidine,arecaidine,arecoline,epicatechin,baicalein,glycyrrhizinate and wogonin in Dayuan Drink.METHODS The analysis was performed on a 35℃thermostatic Syncronis C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray inoization source was adopted in positive and negative ion scanning with select reaction monitoring mode.RESULTS Twenty-eight constituents showed good linear relationships within their own ranges(R2≥0.991 0),whose average recoveries were 95.60%-103.53%with the RSDs of 0.60%-5.45%.CONCLUSION This rapid,simple,selective,accurate and reliable method can be used for the quality control of Dayuan Drink.

AIM: To investigate the changes in peripapillary choroidal thickness(pCT)within 1a of the first episode of acute primary angle closure glaucoma(APACG).METHODS: A prospective cohort study. A total of 31 patients with APACG who admitted to the ophthalmology department of Shijiazhuang People's Hospital from October 2015 to September 2019 were selected, with 31 eyes in attack group, 31 fellow eyes in preclinical group and 30 cases(30 eyes)in control group. pCT of the three groups was measured respectively at the attack period, 1wk, 1, 3, 6mo and 1a after surgery.RESULTS: The pCT of the attack group was thicker than that in the attack period when at 1wk after surgery, and continued to become thinner within the following 1a(P<0.05). The pCT of the attack group was thicker than that of the other two groups during the attack period and at 1wk after surgery, while it became thinner at 1a(P<0.05). In the attack group, the average pCT was positively correlated with the duration of intraocular hypertension and negatively correlated with the anterior chamber depth(P<0.05).CONCLUSION: For patients with first episode of APACG, pCT was diffusely thickened during attack and at 1wk after surgery. The pCT returned to normal at 1mo, while it became thinner at 1a. Furthermore, the average pCT was positively correlated with the duration of intraocular hypertension, and the choroidal thickness may play an important role in the attack of APACG.

Objective: To screen and analyze the factors affecting the prognosis of replacing single missing tooth by autograft tooth, so as to provide reference for clinical judgment of surgical prognosis. Methods: A total of 176 patients (188 teeth) underwent autotransplantation of teeth in the Department of Oral & Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University from January 2017 to December 2019, including 85 teeth of males and 103 teeth of females were involved. The age was (33.0±9.8) years (16-65 years). The possible factors affecting the prognosis of replacing single missing tooth by autograft tooth were summarized and grouped, and the clinical and imaging data were recorded and judged. The surgical records and photographic data from the patients' previous medical records were retrospectively analyzed. The survival analysis method was used for statistical analysis to screen out the factors affecting the cumulative survival rate of transplanted teeth. Results: The 5-year cumulative survival rate of 188 transplanted teeth was 88.4%. Univariate Log-Rank analysis showed that age (P<0.001), sex (P=0.008), smoking (P<0.001), position of recipient area (P<0.001), height of alveolar bone in recipient area (P<0.001), time of donor tooth in vitro (P<0.001), use of donor model (P<0.001) and initial stability (P<0.001) were significantly correlated with cumulative survival rate of transplanted teeth. Multivariate Cox proportional hazard regression analysis showed that smoking (β=-2.812, P=0.049), alveolar bone height (β=1.521, P=0.020), donor time (β=-2.001, P=0.019), use of donor model (β=1.666, P=0.034) and initial stability (β=-1.417, P=0.033) were significantly correlated with the cumulative survival rate of transplanted teeth. Conclusions: The prognosis of autogenous tooth transplantation can be predicted by smoking, height of alveolar bone in recipient area, time of donor teeth in vitro, use of donor model and initial stability. Good prognosis of transplanted teeth can be obtained by using donor model during operation, reducing the time of donor teeth in vitro, taking effective methods to restore alveolar bone height, maintaining good initial stability, and good oral health education after operation.
Adult ; Female ; Humans ; Male ; Prognosis ; Retrospective Studies ; Tooth/transplantation* ; Tooth Loss ; Transplantation, Autologous ; Treatment Outcome ; Young Adult

ObjectiveThere are few studies on whether the occurrence of anti-tuberculosis drug-induced liver injury (ADIH) is associated with the polymorphism of CYP2E gene and methylation level. This study aims to CYP2E1 gene polymorphism and the relationship between the methylation level of the promoter region and ADIH in Mongolian tuberculosis (TB) patients.Methods A total of 135 Mongolian TB patients who received standardized treatment at the Tuberculosis Research Institute of Tongliao City, Inner Mongolia from November 2015 to June 2018 were selected. According to the ADIH criteria, TB patients with liver injury were selected as the ADIH group (n=45), and TB patients without liver injury were matched as the control group based on a ratio of 1∶2 (n=90). DNA extraction and polymerase chain reaction (PCR) were performed to amplify the CYP2E1 gene to determine the CYP2E1 rs2031920 genotype, and to analyze the CYP2E1 gene polymorphism and relationship between ADIH and promoter methylation level.Results There were no significant differences in the distribution of CYP2E1 rs2031920 genotype, C1 and C2 gene frequencies between the ADIH group and the control group (P>0.05). The overall methylation level in the promoter region of CYP2E1 gene in ADIH group (0.711±0.085) was significantly lower than that of the control group (0.759±0.062). Results of Logistic regression showed that the overall methylation level in the promoter region of CYP2E1 gene was the influencing factor for the occurrence of ADIH (P<0.005). For each 0.1 unit increase of methylation level, the risk of ADIH occurrence reduced by 0.388 times, and the OR (95% CI) value was 0.388 (between 0.204 and 0.739).Conclusion The overall methylation level in the promoter region of CYP2E1 gene was reduced in Mongolian ADIH patients, but the polymorphism of CYP2E1 gene was not related to the occurrence of ADIH. These results suggested that CYP2E1 methylation could be applied to the prevention and treatment of ADIH in patients with tuberculosis.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

ObjectiveTo examine the changes in the immune functions of CD8⁺ T cells in the spleen of mice following Echinococcus multilocularis infections at various doses and at different time points. MethodsThe E. multilocularis protoscoleces were collected, and E. multilocularis infection was modeled in mice via the hepatic portal vein at doses of 50 (low-dose), 500 (medium-dose) and 2 000 protoscoleces (high-dose), while physiological saline served as controls. Mouse spleen was isolated 2 (earlystage), 12 (middle-stage) and 24 weeks post-infection (late-stage), and spleen lymphocytes were harvested. The phenotype of memory CD8⁺ T cells and 2B4 expression were quantified in the mouse spleen, and the secretion of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-17A and IL-10 was measured. Results A central-memory phenotype was predominant in the CD8⁺ T cells in the spleen of mice at the early stage of high-dose protoscolece infections, and the proportion of central-memory CD8⁺ T cells was significantly greater in the high-dose group than in the control group (35.50% ± 2.00% vs. 25.90% ± 2.46%, P < 0.01), while a effector- memory phenotype was predominant in the CD8⁺ T cells in the spleen of mice at the late stage of medium- and high-dose protoscolece infections, and the proportions of effector-memory CD8⁺ T cells were significantly greater in the medium- (25.70% ± 4.12%) and high-dose group (28.40% ± 4.12%) than in the control group (10.50% ± 6.45%) (P < 0.05). The proportions of the central-memory CD8⁺ T cells were significantly higher in the high-dose group than at middle and late stages than at the early stage (P < 0.01), and the proportion of effector-memory CD8⁺ T cells was significantly greater in the high-dose group at the late stage than at early and middle stages (P < 0.05). The secretion of IFN-γ and IL-17A by spleen CD8⁺ T cells was elevated in the low- and medium-dose groups at the early stage of infection, and high-dose protoscolece infection promoted the secretion of IFN-γ and TNF-α by spleen CD8⁺ T cells; however, the levels of IFN-γ and TNF-α were significantly lower at the late stage than at the early and middle stages (P < 0.05). In addition, high 2B4 expression was detected in spleen CD8⁺ T cells in the middle- and high-dose groups at the late stage of infection, and the 2B4 expression was significantly higher in the medium(4.73% ± 1.56%) and high-dose groups (4.94% ± 1.90%) than in the low-dose group (2.49% ± 0.58%) and the control group (2.92% ± 0.60%) (P < 0.05). Conclusions E. multilocularis may be killed and eliminated through the host immune responses at the middle and late stages of low- and medium-dose protoscolece infections, while high-dose protoscolece infections may trigger the upregulation of 2B4 expression in mouse spleen CD8⁺ T cells at the late stage, which leads to immune exhaustion and the resultant chronic infections.