Nomogram for predicting 5-year metabolic dysfunction-associated steatotic liver disease risk: retrospective cohort study.

OBJECTIVE: To create a nomogram-based model to estimate the Chinese population's 5-year risk of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We randomly divided 7582 participants into two groups in a 7:3 ratio: one group was assigned to work with the training set, which consisted of 5307 cases, and the other group was assigned to validate the model using 2275 cases. The least absolute shrinkage and selection operator (LASSO) model was employed to ascertain the variables with the highest correlation among all potential variables. A logistic model was constructed by incorporating these selected variables, which were subsequently visualized using a nomogram. The discriminatory ability, calibration, and clinical utility of the model were assessed using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS: During the 5-year follow-up, 1034 (13.64%) total participants were newly diagnosed with MASLD. Using 8 variables (gender, body mass index, waist, hemoglobin, alanine aminotransferase, uric acid, triglycerides and high-density lipoprotein) , we built a 5-year MASLD risk prediction model. The nomogram showed an area under the ROC of 0.795 (95% confidence intervals (CI): 0.779-0.811) in the training set and 0.785 (95% CI: 0.760-0.810) in the validation set. The calibration curves revealed a 5-year period of agreement between the observed and predicted MASLD risks. DCA curves illustrated the practicality of this nomogram over threshold probability profiles ranging from 5% to 50%. CONCLUSIONS: We created and tested a nomogram to forecast the risk of MASLD prevalence over the next 5 years.

Construction of a risk model based on N6 -methyladenosinerelated lncRNAs for predicting the prognosis of breast cancer.

N6-methyladenosine modification and lncRNAs are closely related to the prognosis and immunotherapy response of breast cancer patients. LncRNAs related to m6 A-associated genes were predicted based on coexpression analysis of the TCGA database. We established a novel 7-m6 A-associated lncRNA signature for predicting patient prognosis and validated it. The model was significantly correlated with survival time and survival status and was an independent predictor of overall survival (OS). Except for the M1 disease group, the model had good predictive value for OS in different subgroups. We constructed a prognostic model based on 7 m6 A-associated lncRNAs in breast cancer. This model could serve as an independent prognostic factor with tremendous predictive ability for breast cancer patients.

Robust Fusion Kalman Estimator of the Multi-Sensor Descriptor System with Multiple Types of Noises and Packet Loss.

Under the influence of multiple types of noises, missing measurement, one-step measurement delay and packet loss, the robust Kalman estimation problem is studied for the multi-sensor descriptor system (MSDS) in this paper. Moreover, the established MSDS model describes uncertain-variance noises, multiplicative noises, time delay and packet loss phenomena. Different types of noises and packet loss make it more difficult to build the estimators of MSDS. Firstly, MSDS is transformed to the new system model by applying the singular value decomposition (SVD) method, augmented state and fictitious noise approach. Furthermore, the robust Kalman estimator is constructed for the newly deduced augmented system based on the min-max robust estimation principle and Kalman filter theory. In addition, the given estimator consists of four parts, which are the usual Kalman filter, predictor, smoother and white noise deconvolution estimator. Then, the robust fusion Kalman estimator is obtained for MSDS according to the relation of augmented state and the original system state. Simultaneously, the robustness is demonstrated for the actual Kalman estimator of MSDS by using the mathematical induction method and Lyapunov's equation. Furthermore, the error variance of the obtained Kalman estimator is guaranteed to the upper bound for all admissible uncertain noise variance. Finally, the simulation example of a circuit system is examined to illustrate the performance and effectiveness of the robust estimators.

Robust Sliding Mode Control for Stochastic Uncertain Discrete Systems with Two-Channel Packet Dropouts and Time-Varying Delays.

In this paper, the control problem is investigated for discrete time-varying delayed systems with stochastic uncertainty, external disturbance, and two-channel packet dropouts. Sliding mode functions with packet loss probabilities are proposed for the packet loss problem in the sensor-controller channel and the controller-actuator channel. Furthermore, by employing the Lyapunov-Krasovskii functional, some new stability conditions are established in terms of solvable linear matrix inequalities (LMIs), and H∞ performance is analyzed for the sliding mode motion of the system. Meanwhile, a sliding mode controller is designed to drive the system state to the pre-designed sliding surface. Moreover, the designed controller can be robust for two-channel packet dropouts, time-varying delays, stochastic uncertainty and external disturbance. Finally, two numerical examples are given to demonstrate the feasibility of the proposed theoretical method.

Serum lutein is a promising biomarker for type 2 diabetes mellitus and diabetic kidney disease in the elderly.

OBJECTIVE: To investigate the relationship between serum lutein and type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD) in elderly individuals. METHODS: A total of 60 T2DM patients over 60 years were subgrouped into a DKD group and a non-DKD group according to their urinary microalbumin-to-creatinine ratio (UACR), while 30 age-matched non-T2DM patients were recruited in the control group. Baseline characteristics, laboratory examination results, and serum lutein levels were compared, and their correlations were analyzed. Receiver operating characteristic (ROC) curves were plotted to identify the diagnostic potential of lutein in T2DM and DKD. RESULTS: The lutein level in the T2DM group was significantly lower than that in the control group and was also significantly lower in the DKD group than in the non-DKD group (p < 0.001). Lutein levels were negatively correlated with body mass index, glycosylated hemoglobin, fasting blood glucose, triglyceride, and UACR and positively correlated with high-density lipoprotein cholesterol (p < 0.05). T2DM patients were divided into four groups according to the quartile of their lutein level. The proportion of T2DM and DKD gradually decreased with increasing lutein levels (p < 0.001). The area under the ROC curve of serum lutein in diagnosing T2DM and DKD was 0.880 and 0.779, respectively, with corresponding cut-off values of 0.433 µmol/L and 0.197 µmol/L (p < 0.001). CONCLUSION: The serum level of lutein is negatively correlated with the incidence of T2DM and DKD in the elderly and can serve as a diagnostic marker for T2DM and DKD.

A Risk Assessment Tool for Identifying Osteoporosis in Older Women with Type 2 Diabetes Mellitus.

PURPOSE: To develop a simple and clinically useful assessment tool for osteoporosis in older women with type 2 diabetes mellitus (T2DM). METHODS: A total of 601 women over 60 years of age with T2DM were enrolled in this study. The levels of serum sex hormones and bone metabolism markers were compared between the osteoporosis and non-osteoporosis groups. The least absolute shrinkage and selection operator regularization (LASSO) model was applied to generate a risk assessment tool. The risk score formula was evaluated using receiver operating characteristic analysis and the relationship between the risk score and the bone mineral density (BMD) and T-value were investigated. RESULTS: Serum sex hormone-binding globulin (SHBG), cross-linked C-telopeptide of type 1 collagen (CTX), and osteocalcin (OC) were significantly higher in the osteoporosis group. After adjustment for age and body mass index (BMI), SHBG was found to be correlated with the T-value or BMD. Then, a risk score was specifically generated with age, BMI, SHBG, and CTX using the LASSO model. The risk score was significantly negatively correlated with the T-value and BMD of the lumbar spine, femoral neck, and total hip (all P<0.05). CONCLUSION: A risk score using age, BMI, SHBG, and CTX performs well for identifying osteoporosis in older women with T2DM.

Differences in early-phase insulin secretion and glucose disposition index between aged and middle-aged patients with newly diagnosed type 2 diabetes.

AIM: This cross-sectional study aimed to investigate the differences in ß-cell function and insulin sensitivity between newly diagnosed aged and middle-aged type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 206 newly diagnosed T2DM patients aged ≥60 years (A-DM group) and 206 newly diagnosed sex- and glycated hemoglobin-matched T2DM patients aged <60 years (MA-DM group) were recruited. All patients underwent the 75-g oral glucose tolerance test. Plasma glucose, lipid profiles, liver and renal function, glycated hemoglobin, and insulin were measured. Homeostasis model assessment for insulin resistance, quantitative insulin sensitivity check index, area under the curve of glucose during 0-30 min (GluAUC30) × area under the curve of insulin during 0-30 min (InsAUC30) and ß-cell function indexes were calculated. RESULTS: The mean age of the total 412 patients (356 men and 56 women) was 59.76 ± 13.32 years. There were no significant differences in GluAUC120 between the two groups (106.89 ± 27.70 in A-DM vs 108.32 ± 27.58 in MA-DM; P = 0.6), but ΔI30/ΔG30, InsAUC30 and GluAUC30 × InsAUC30 levels were significantly higher in the A-DM group than in the MA-DM group (3.55 ± 4.54 vs 2.53 ± 3.83; P = 0.014, and 39.19 ± 32.19 vs 32.71 ± 28.81; P = 0.032, 675.05 ± 475.60 vs 584.56 ± 450.23; P = 0.048, respectively). The glucose disposition index (GDI) of the A-DM group was statistically higher than that of the MA-DM group (0.38 ± 0.40 vs 0.30 ± 0.35; P = 0.018). Age was positively associated with ΔI30/ΔG30 (r = 0.117; P = 0.017) and GDI (r = 0.147; P = 0.003), but had no correlation with InsAUC30, InsAUC120 or GluAUC30 × InsAUC30. After multiple adjustments for confounders, including sex, body mass index, glycated hemoglobin, triglyceride, total cholesterol and high-density lipoprotein cholesterol, age was positively associated with ΔI30/ΔG30, InsAUC30, InsAUC120, GluAUC30 × InsAUC30 and GDI. CONCLUSIONS: Aged patients have relatively higher early-phase insulin secretion and GDI than middle-aged patients in newly diagnosed T2DM. Geriatr Gerontol Int 2020; ••: ••-••.

Naringenin Cocrystals Prepared by Solution Crystallization Method for Improving Bioavailability and Anti-hyperlipidemia Effects.

Naringenin exerts anti-inflammatory, hypolipidemic, and hepatoprotective effects; however, it shows low oral bioavailability because of poor water solubility. In this work, cocrystals of naringenin were formed to address these issues. Using the solution crystallization method, various naringenin cocrystals were prepared with different cocrystal coformers, including naringenin-nicotinamide, naringenin-isonicotinamide, naringenin-caffeine, naringenin-betaine, and naringenin-L-proline. The formation of these cocrystals was assayed by using DSC, XRD, and FT-IR spectroscopy. The stoichiometric ratio of naringenin and the CCFs in the corresponding cocrystals was investigated by NMR. The solubility of naringenin, as well as its dissolution rate, was markedly improved by forming cocrystals. The oral bioavailability of naringenin administered as naringenin-L-proline and naringenin-betaine cocrystals was achieved significantly greater than that of pure naringenin (p < 0.05). In particular, the Cmax of naringenin-L-proline and naringenin-betaine cocrystals were 2.00-fold and 3.35-fold higher, and the AUC of naringenin-L-proline and naringenin-betaine cocrystals were 2.39-fold and 4.91-fold, respectively, higher than pure naringenin in rats. With the naringenin-betaine cocrystals for oral delivery, the drug distribution in the liver was significantly increased compared to pure naringenin. Accordingly, the naringenin-betaine cocrystals showed improved anti-hyperlipidemia effects on the C57 BL/6J PNPLA3 I148M transgenic mouse hyperlipidemia model. Collectively, cocrystal formation is a promising way to increase the bioavailability of naringenin for treating hyperlipidemia.

Peptidome analysis reveals the involvement of endogenous peptides in mouse pancreatic dysfunction with aging.

Type 2 diabetes (T2D) is a glucose regulation disorder that has significantly enhanced mortality and the global disease burden. The prevalence of T2D has increased worldwide and is higher in the elderly. The function of pancreatic islets decreases with age, which is one important reason for the occurrence of diabetes in the elderly. Recently, peptidome analysis has attracted attention. However, the role of age-related peptides in pancreatic dysfunction has not been investigated extensively. Here, we conducted a comparison of endogenous peptides between pancreas from adult and aging mice by liquid chromatography tandem mass spectrometry (LC-MS/MS). A total of 2,089 peptides originating from 1,280 protein precursors were identified, of which 232 were upregulated and 183 were downregulated in the aging mice (fold change ≥ 2 and p < 0.05), suggesting that the expression of pancreatic peptides in mice varied with age. The molecular weight of most peptides was <3.0 kDa, and the isoelectric point distribution had a bimodal characteristic. Further analysis of cleavage site patterns indicated that proteases cleaved pancreatic proteins according to their rules. Moreover, Gene Ontology and pathway analyses showed that the differentially expressed peptides potentially had specific effects on pancreatic dysfunction. Some differential peptides were located within the domains of precursor proteins that were closely associated with the development of diabetes. We believe that our research may advance the current understanding of pancreas-derived peptides and that certain peptides may be involved in the etiology of diabetes.

Age-related change in thyroid-stimulating hormone: a cross-sectional study in healthy euthyroid population.

This cross-sectional study aimed to examine changes in thyroid-stimulating hormone (TSH) concentration over age in China and investigate relationship between TSH and risk factors for cardiovascular disease (CVD) among euthyroid subjects. TSH, free triiodothyronine (FT3), free thyroxine (FT4), blood lipid, and glucose were measured. 7,693 individuals were subdivided into different age groups. Associations between TSH and CVD risk factors [age, body mass index (BMI), systolic and diastolic blood pressure, total cholesterol (TC), triglycerides, low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) and fasting plasma glucose (FPG)] were evaluated with Pearson correlation analysis. Results showed that 2.5th percentile for TSH was consistent across age groups, whereas 97.5th percentile increased in subjects older than 40 years with upper limit being 6.83 mIU/L in subjects aged 60-69 years and 8.07 mIU/L in those older than 70 years. The age-specific upper limits reclassification rate was higher in all age bands as compared to the common cut-off value. TSH was positively associated with age, SBP, DBP, TC and LDL-C and negatively with FT3 and FT4. Serum TSH within new reference range had a linear correlation with SBP, TC and LDL-C in subjects aged <60 years. There were no significant differences in BMI, blood pressure, lipid profile or FPG among subjects 60-69 and older than or equal to 70 years. Elevated TSH within new reference range is associated with risk factors for CVD in subjects aged <60 years. Thus, there might be age-related difference in the relationship between CVD risk factors and elevated serum TSH.

Non-alcoholic fatty liver disease is an influencing factor for the association of SHBG with metabolic syndrome in diabetes patients.

Metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD) have been identified as risk factors affecting serum sex hormone binding globulin (SHBG) levels. We conducted this cross-sectional study to delineate whether MS or NAFLD has more impact on circulating SHBG levels in type 2 diabetes (T2D) patients. Anthropometric and biochemical parameters including serums SHBG, testosterone (TT), liver enzymes, lipids, insulin, C-peptide and plasma glucose were measured. Regardless of the MS status, SHBG level was significantly lower in NAFLD patients than in non-NAFLD patients (P < 0.001). In the multiple linear regression analysis, lower serum SHBG level was strongly correlated with a higher incidence of NAFLD, but not MS components. In logistic regression analyses, after adjusted for age, sex, duration of diabetes, smoking status, and alcohol use, the ORs and 95%CI for presence of MS was 2.26 (95%CI 1.91-2.68) and for presence of NAFLD was 6.36 (95%CI 4.87-8.31) with per one SD decrease in serum SHBG (both P < 0.001). In conclusion, lower serum SHBG is associated with a higher prevalence of NAFLD, compared with MS and other metabolic disorders, in T2D patients. NAFLD might be an important influencing factor for the association of circulating SHBG with MS in T2D patients.

[Isolation and identification of berberine from endophytic fungi HL-Y-3].

The endophytic fungi HL-Y-3, which was isolated from the healthy leaves of Coptis chinensis, produced berberine when grown in the PDA culture medium. The presence of berberine was confirmed by the chromatographic and spectroscopic analyses. The yield of berberine was recorded as 9.313 µg•g⁻¹ by HPLC. The strain HL-Y-3 was identified as Alternaria sp.by morphological observation and 5.8S rDNA-ITS sequence analysis.The separation and purification of constituents were performed by PTLC. The mass spectrometry (MS) of the analyte was shown to be identical with authentic berberine.Further analysis with nuclear magnetic resonance (NMR) spectroscopy to showed that the chemical structure of the fungal berberine was identical with authentic berberine. The research provided new resources for the utilization of berberine.

Optimization of Supercritical Fluid Extraction of Total Alkaloids, Peimisine, Peimine and Peiminine from the Bulb of Fritillaria thunbergii Miq, and Evaluation of Antioxidant Activities of the Extracts.

Supercritical fluid extraction (SFE) was used to extract total alkaloids, peimisine, peimine and peiminine from the bulb of Fritillaria thunbergii Miq. The antioxidant capacity of the extracts was evaluated by DPPH radical scavenging activity (DPPH-RSA), ABTS radical scavenging activity (ABTS-RSA) and ferric reducing capacity (FRAP) assay. A central composite design (CCD) with four variables and five levels was employed for optimization of process parameters, and response surface plots were constructed in accordance with a second order polynomial model. Under optimal conditions of 3.0 h, 60.4 °C, 26.5 MPa and 89.3% ethanol, the highest yields were predicted to be 3.8 mg/g for total alkaloids, 0.5 mg/g for peimisine, 1.3 mg/g for peimine and 1.3 mg/g for peiminine, and the antioxidant capacity of extracts displayed EC50, DPPH value of 5.5 mg/mL, EC50, ABTS value of 0.3 mg/mL and FRAP value of 118.2 mg ascorbic acid equivalent (AAE)/100 g.

The effect of Helicobacter pylori eradication therapy on the development of gastroesophageal reflux disease.

BACKGROUND: It is uncertain whether the Helicobacter pylori eradication therapy makes a role in the progression of gastroesophageal reflux disease (GERD). METHODS: A meta-analysis was undertaken to investigate the effect of H pylori eradication therapy on the development of GERD. RESULTS: Overall, 16 cohort studies were included. The authors demonstrated that H pylori eradication had no significant effect on the occurrence of GERD in these cohort studies (odds ratio = 0.87, 95% confidence interval = 0.66-1.14, I = 32.4%, P = 0.103). CONCLUSIONS: In general, H pylori eradication has no significant effect on the development of GERD in the long term. However, eradication therapy should be taken once there is H pylori infection, because H pylori infection is acknowledged to be a major cause of acute and chronic gastritis and peptic ulcer diseases and has been established as a definite etiologic factor for gastric cancer.

Characterization of the complete mitochondrial genome of the black cutworm Agrotis ipsilon (Lepidoptera: Noctuidae).

The complete mitochondrial genome of the black cutworm Agrotis ipsilon (Lepidoptera: Noctuidae) was determined (GenBank accession No. KF163965). The length of this mitochondrial genome is 15,377 bp with an A + T content of 82.5%. There are 37 typical animal mitochondrial genes, that is, 13 protein-coding, 2 rRNA and 22 tRNA gene and an A + T-rich region. The tRNA gene trnM was rearranged to the upstream of the trnI-trnQ-trnM cluster compared with the pupative ancestral arrangement of insects. All protein-coding genes start with ATN start codon except for the gene cox1, which uses CGA as in other lepidopteran species. Ten protein-coding genes stop with termination codon TAA, whereas three protein-coding gene use incomplete stop codon T. The A + T-region is located between rrnS and trnM with a length of 332 bp and A + T content of 94.88%.

Simultaneous determination of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside, senkyunolide I in Beagle dogs plasma by UPLC-MS/MS and its application to a pharmacokinetic study after Oral Administration of Shaofu Zhuyu Decoction.

In this present study, a sensitive and rapid UPLC-MS/MS method was developed for simultaneous quantification of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside and senkyunolide I in Beagle dog plasma after oral administration of the Shao-Fu-Zhu-Yu Decoction. Chloramphenicol and clarithromycin were used as internal standards. Plasma samples were processed by protein precipitation with methanol. The separation was performed on an Acquity BEH C18 column (100mm×2.1mm, 1.7µm) at a flow-rate of 0.4mL/min, using 0.1% formic acid-acetonitrile as mobile phase. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. After validation, this method was successfully applied to a pharmacokinetic study. The results showed that the apparent plasma clearance of paeoniflorin, albiflorin, typhaneoside and senkyunolide I were significantly higher than others. Double peak was observed in plasma concentration curves of tetrahydropalmatine, the ferulic acid had a good absorption in Beagle dog plasma, and senkyunolide I was detected in plasma from the first blood sampling time (15min) and rapidly reached Tmax. The compound of typhaneoside has a low bioavailability according to the results.

The complete mitogenome of the turnip moth Agrotis segetum (Lepidoptera: Noctuidae).

Abstract The complete mitochondrial genome (mitogenome) of the turnip moth Agrotis segetum (Lepidoptera: Noctuidae) was determined (GenBank accession No. KC894725). This is the first sequenced mitogenome from the subfamily Noctuinae of Noctuidae. The length of this mitogenome is 15,378 bp with a A+T content of 80.7%. There are 37 typical animal mitochondrial genes and a A+T-rich region. The tRNA gene trnM was the only rearranged gene compared with the pupative ancestral arrangement of insects. All protein-coding genes start with ATN start codon except for the gene cox1, which uses CGA as in other lepidopteran species. Ten protein-coding genes stop with termination codon TAA, whereas three protein-coding gene use incomplete stop codon T. The A+T-region is located between rrnS and trnM with a length of 332 bp and A+T content of 93.5%.

Network-based biomarkers for cold coagulation blood stasis syndrome and the therapeutic effects of shaofu zhuyu decoction in rats.

In this study, the reverse docking methodology was applied to predict the action targets and pathways of Shaofu Zhuyu decoction (SFZYD) bioactive ingredients. Furthermore, Traditional Chinese Medicine (TCM) cold coagulation blood stasis (CCBS) syndrome was induced in female Sprague-Dawley rats with an ice-water bath and epinephrine, and SFZYD was used to treat CCBS syndrome. A metabolomic approach was used to evaluate changes in the metabolic profiles and to analyze the pharmacological mechanism of SFZYD actions. Twenty-three potential protein targets and 15 pathways were discovered, respectively; among these, pathways are associated with inflammation and immunological stress, hormone metabolism, coagulation function, and glycometabolism. There were also changes in the levels of endogenous metabolites of LysoPCs and glucuronides. Twenty endogenous metabolites were identified. Furthermore, the relative quantities of 6 endogenous metabolites in the plasma and 5 in the urine were significantly affected by SFZYD (P < 0.05). The pharmacological mechanism of SFZYD was partially associated with glycerophospholipid metabolism and pentose and glucuronate interconversions. In conclusion, our findings demonstrated that TCM CCBS pattern induced by ice water and epinephrine was complex and related to multiple metabolic pathways. SFZYD did regulate the TCM CCBS by multitargets, and biomarkers and SFZYD should be used for the clinical treatment of CCBS syndrome.

Adaptive synchronization and parameter identification of chaotic system with unknown parameters and mixed delays based on a special matrix structure.

In this paper, we investigate the synchronization and parameter identification of chaotic system with unknown parameters and mixed delays. A new approach is proposed for designing a controller and a update rule of unknown parameters based on a special matrix structure, and the synchronization and the parameter identification are realized under the controller and the update rule. Numerical simulations are carried out to confirm the effectiveness of the approach. A significant advantage is that the process of designing a controller and a update rule become very clear and easy by the proposed approach.

UHPLC-MS simultaneous determination and pharmacokinetic study of three aromatic acids and one monoterpene in rat plasma after oral administration of Shaofu Zhuyu decoction.

We developed a sensitive and rapid method for determination of ferulic acid, caffeic acid, vanillic acid, and paeoniflorin in rat plasma based on ultra high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The separation of the four compounds was carried out on an AcQuity UHPLC™ BEH C18 column using a mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). Electrospray ionization in positive and negative ion mode and multiple reaction monitoring was used to identify and quantify active components. All calibration curves gave good linearity (r > 0.991) over the concentration range from 4.24-2875 ngmL(-1) for all components. The precision of the in vivo study was evaluated by intraday and interday assays and the percentages of RSD were all within 10.6%. The recovery ranged from 60.2 to 77.9%. The method was successfully applied to pharmacokinetic study of all three aromatic acids and one monoterpene in rat plasma. Furthermore, we compared the pharmacokinetics profile of the four compounds in normal and primary dysmenorrhea rats' plasma following oral administration of Shaofu Zhuyu decoction (SFZYD) and its ethanol supernatant extract (SFE).