G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Large-scale gene expression profiling generates or integrates massive data of gene expression under drug induction and employs artificial intelligence algorithms for pattern matching and association analysis. This approach facilitates the identification of complex relationships and functional networks between drugs, genes, and diseases, thereby significantly advancing drug research. Traditional Chinese medicine(TCM), with its characteristic multi-component, multi-target, and multi-pathway mechanisms, poses challenges to conventional methodologies in the comprehensive elucidation of its biological effects. The drug discovery strategy that combines large-scale gene expression profiling with artificial intelligence offers distinct advantages since it does not need the prior knowledge of specific drug targets or mechanisms. This article comprehensively reviews the innovative applications of large-scale gene expression profiling in TCM research as well as the recent advancements in the development of these technologies, the optimization of pattern matching algorithms, and the construction of related databases. In summary, the integration of large-scale gene expression profiling with artificial intelligence provides a powerful hypothesis-generating tool for the modern application and theoretical innovation of TCM.
Medicine, Chinese Traditional/methods* ; Gene Expression Profiling/methods* ; Humans ; Artificial Intelligence ; Drugs, Chinese Herbal/pharmacology* ; Algorithms ; Animals

Objective To explore the correlation between childhood trauma and plasma adiponectin levels in patients with depression.Methods A total of 121 patients with depression and 39 healthy controls(control group)were enrolled.Childhood trauma questionnaire(CTQ-SF)was used to assess the experience of childhood abuse and neglect,and the patients with depression were divided into trauma group(n=53)and non-trauma group(n=68)according to the CTQ-SF score.The 17-item Hamilton depression scale-17(HAMD17)and the Hamilton anxiety scale(HAMA)were used to evaluate the severity of depression and anxiety symptoms,respectively.Plasma adiponectin levels of subjects were measured by enzyme-linked immunosorbent assay.Results The plasma adiponectin level of trauma group[3.82(2.44,4.92)μg/mL]was significantly lower than that of non-trauma group[4.64(2.98,6.43)μg/mL,P=0.01]and the control group[6.29(4.54,7.51)μg/mL,P＜0.01].The plasma adiponectin level of non-trauma group was lower than that of the control group(P＜0.01).Correlation analysis showed that plasma adiponectin level in patients with depression was negatively correlated with childhood trauma(r=-0.34,P＜0.01).Multivariate linear regression analysis showed that plasma adiponectin level was negatively correlated with childhood trauma scores in patients with depression(β=-0.05,P＜0.01).Conclusions Patients with depression who have experienced childhood trauma have lower plasma levels of adiponectin,and childhood trauma may be associated with decreased plasma adiponectin levels in patients with depression.

To investigate the effects and mechanism of the combination of Morus alba L. (Sangzhi) alkaloids(SZ-A) and metformin (Met) on glucose metabolism in type 2 diabetic mice, KKAy mice were divided into four groups according to the glucose and lipid indexes: control group (control), Morus alba L. (Sangzhi) alkaloids group (SZ-A, 100 mg·kg^-1), metformin group (Met, 100 mg·kg^-1) and combined administration group (combination, Comb, 100 mg·kg^-1 SZ-A + 100 mg·kg^-1 Met). All groups were administered by gavage once daily for 7 weeks accompanied with monitoring food intake, water intake, body weight as well as glycemia. Additionally, oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and oral sodium pyruvate tolerance test (OPTT) were performed at week 2, week 5, week 6, respectively. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (00004332). We determined the weight and lipid content of liver, and then performed the histopathological analysis after sacrificed. Furthermore, Western blot assay was used to detect the protein levels of key molecules of PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue. Compared to the SZ-A or Met monotherapy group, SZ-A + Met significantly improved the glucose metabolism disorder, which was showed in reduced food intake, water intake, the level of fasting blood glucose, postprandial blood glucose and glycosylated hemoglobin A1c (HbA1c) of KKAy mice, as well as improved glucose tolerance, enhanced insulin sensitivity and inhibited gluconeogenesis. In addition, SZ-A + Met obviously up-regulated the protein expression levels in PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue of KKAy mice. Moreover, the liver lipid accumulation and blood aminotransferase level of KKAy mice in the combined administration group were significantly reduced. Therefore, we concluded that the combination of SZ-A and Met improved glucose metabolism and inhibited the occurrence and development of T2DM via promoting glucose uptake and utilization, suggesting that the combination of SZ-A and Met is a more useful treatment for T2DM.

Objective To explore the dosimetric differences of radiotherapy plan for cervical cancer with 4 different fluence smoothing (FS) parameters using Monaco treatment planning system (Monaco TPS). Methods Fifteen patients with ⅠB2 stage cervical cancer in our hospital were enrolled in this study. And a 2 Volumetric Modulated Arc Therapy (VMAT) plan for each patient were completed by Monaco 5.11 TPS according to the X-Ray Voxel Monte Carlo (XVMC) method. For each plan was optimized by FS function, with the level of Off, Low, Medium and High. To compare the difference of plan optimization time, conformity index (CI), Homogeneity index (HI), D_mean, D_min, D_2% of PTV，dose to the organ at risk (OAR)，the number of Segments# and MU#，estimated total delivery time (ETDT), quantum Efficiency (QE) of the plans, the formation of Segments# with the same angle and verification of inserting 729 two-dimensional matrix into PTW octavius 4D module of different FS function levels, with the precondition of the Prescription isodose curve covering 95% of the target area. The data was analysed by multivariate factor analysis with the application of SPSS, and P < 0.05 was considered as statistically significant. And the Planned revenue score of different FS levels was also calculated. Results Except for the D_min of PTV (the lowest value is (32.09 ± 0.26) Gy for the Off group, and the highest value is (35.98 ± 0.42) Gy for the High group), V₄₀ of the rectum (the lowest value in the Medium group is 55.88% ± 2.02%, and the highest value in the High group was 61.90% ± 2.98%) and bladder (the lowest value was 45.01% ± 2.08% in the Medium group, and the highest value is 50.45% ± 1.98% in the High group), the V₂₀ (the lowest value High group was 49.05% ± 1.98%, the highest value Off group was 56.52% ± 1.75%) of femoral head (P < 0.05), there was no significant difference of the dose assessment results for PTV and OARs in 4 different FS function levels. In the High level, the ETDT, QE and MU# were showed better than other groups evidently, however, the number of Segments# showed no significant difference. The plan validation results was increased with the improvement of FS function level, and the level of High was considered to be the optimal. To compare the score of overall benefits of the plan, the level of Medium (−17.18 ± 0.05) got the highest score, and the Low group (−17.58 ± 0.05) and the High group (−17.42 ± 0.06) have similar scores, and Off group (−18.81 ± 0.08) has the lowest score. Conclusion Different FS levels of the Monaco 5.11 TPS can optimize the radiotherapy plan for cervical cancer, but the level of Medium is considered to be the most applicable.

Based on the serum medicinal method, this study aims to investigate the migrating components of Yougui Yin in the blood after intragastric administration, and to provide reference for the basic research of its pharmacodynamics. The kidney deficiency rat model was replicated by adenine method. Normal rats and model rats were administered orally for a single gavage of Yougui Yin. The components in blood were rapidly analyzed and identified by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and multiple reaction monitoring(MRM), and the migrating components in blood of Yougui Yin were explored by multivariate statistical analysis. The results showed that there were 42 characteristic peaks in the plasma of normal rats by UPLC-Q-TOF-MS technology and 13 chemical components were identified, including 6 alkaloids, 2 flavonoids, 2 triterpenoid saponins, 1 iridoid, 1 phenylpropanoid and 1 monoterpenoid. There were 22 characteristic peaks in the plasma of kidney-deficiency rats, and 12 chemical components were identified, including 2 iridoids, 6 alkaloids, 2 flavonoids, 1 monoterpenoid and 1 triterpenoid saponin. Verbascoside, isoacteoside, acteoside, pinoresinoldiglucoside, loganin and morroniside were identified by MRM both in the plasma of normal rats and kidney-deficiency rats. Compared with 85 monomer components in Yougui Yin, 17 common prototype components were found by UPLC-MS in the plasma of normal rats and kidney deficiency rats, including verbascoside, isoacteoside, acteoside, rehmapicrogenin derived from Rehmanniae Radix Praeparata, pinoresinol diglucoside and geniposidic acid from Eucommiea Cortex, loganin and morroniside derived from Corni Fructus, mesaconine, benzoylmesaconine, benzoylaconitine, benzoylhypacoitine, mesaconitine, aconitine derived from Aconiti Lateralis Radix Praeparata, liquiritin, isoliquiritin and glycyrrhizic acid derived from Glycyrrhizae Radix et Rhizoma. Thirty-one metabolites of medicinal ingredients not found in the plasma of adenine-induced kidney deficiency rats were also detected in the plasma of normal rats. Twelve metabolites of medicinal materials not found in the plasma of normal rats were detected in the plasma of kidney deficiency rats. The results of the study provide reference for explaining the material basis and mechanism of Yougui Yin in the treatment of kidney deficiency.
Adenine ; Animals ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Drugs, Chinese Herbal/toxicity* ; Kidney ; Rats ; Tandem Mass Spectrometry ; Technology

Aim To explore the mechanism of Fluspirilene inhibiting HCC through decreasing the expression of Akt.Methods The difference of mRNA was verified by the test of protein expression between Fluspirilenc treatment group and control group by HCC experiment in vivo and vitro, including Western blot, IHC after mRNA array.Results Akt expression was lower in Fluspirilene treatment group than that in control group by mRNA array.Protein expression of Akt, phosphorylate-CDK2 and phos- phorylate-Rb decreased massively in Fluspirilene treatment group in a concentration-dependent manner in HepG2 and Huh7 cells by Western blotting compared with those in control group.Declined expression of phosphorylate-Akt was proved in a concen- tration-dependent manner in xenograft tumor tissues in Fluspirilene treatment group compared with that in control group in IHC test.Conclusions Fluspirilene inhibits HCC by decreasing significantly the protein expression of Akt, phosphorylat-Akt, phos- phorylate-CDK2 and phosphorylate-Rb.

Erythropoietin is an endogenous 34 000 glycoprotein hormone composed of 165 amino acids. EPO is mainly derived from the liver of the fetus and synthesized in the kidney after birth, but is secreted by the liver, kidney, brain, reproductive system, bone marrow macrophage and mammary gland. The production of EPO is regulated by hypoxia-inducible factors. EPO can significantly stimulate the proliferation and survival of red blood cells and promote hematopoiesis; it has been used clinically to treat chronic renal anemia, anemia caused by bone marrow tumors and myelodysplasia. EPO has a wide range of physiological functions and it is found in all systems of animal life. Apart from promoting hematopoiesis, EPO also promotes angiogenesis, and shows brain protection, kidney protection, heart protection, regulation of metabolism, regulation of inhalation, protection of the digestive system and reproductive system. Animals without EPO can hardly survive. It illustrates that EPO plays an important role in life.

OBJECTIVE: To develop the visual uroflow scale (VUS), analyze the relationship of VUS score and index of free uroflowmetry, assess urination function preliminarily and improve the work efficiency in the clinic. METHODS: Male lower urinary tract symptoms (LUTS) patients, who attended the Department of Urology in Peking University People's Hospital from March 2016 to March 2017, were assessed for their urination function according to the Visual Uroflow Scale without help from clinicians before undertaking a free uroflowmetry test. And afterwards, a free uroflowmetry was undertaken, and variables including maximal flow rate (Qmax), the average flow rate (Qave) and voiding volume (VV) was obtained. During the study, 124 cases were collected and 53 cases met the inclusion and exclusion criteria and were included in the study cohort. The Spearman correlation analysis was used for analyzing the correlation of VUS scores with free uroflowmetry variables and age. The validity of VUS was evaluated. RESULTS: Most of the patients could choose the very figure matched with self-condition by first instinct without any help from the clinician. The data were analyzed by Spearman correlation analysis. In the present study, voiding time was positively correlated with the VUS score (correlation coefficient, 0.62, P < 0.05). In the present cohort, the patients chose the third and fourth figures to take longer time to urinate, implying worse LUTS situation. Flow time and VUS scores were positively correlated (correlation coefficient, 0.61, P < 0.05). The patients with higher VUS scores would spend more time on urinate, no matter how long urinary hesitation was. Both Qmax and Qave were negatively correlated with the VUS score (correlation coefficient －0.54, －0.62, P < 0.05). The study illustrated that the VUS score suggested that the Qmax basically and further reflected the urination function. And its relationship to age revealed the decreased urination function of aging male, which had reached a consensus. CONCLUSION Development of VUS has helped the clinician assess the urination function preliminarily at the first time. Patients are assessed for a VUS score before getting surgery or receiving the drug for treatment, and can be re-assessed after. The VUS score can provide an objective quantitative basis to evaluate the treatment efficacy. In addition, considering that it is convenient, timesaving and easy to understand, the VUS is available for follow-up.
Cohort Studies ; Humans ; Lower Urinary Tract Symptoms ; Male ; Urination ; Urodynamics

Objective To study the portal venous systemic thrombosis (PVST) in early acute pancreatitis (AP) and its correlations with the classification and severity of AP. Methods A total of 396 patients with AP were admitted to the affiliated hospital of north sichuan medical college from January 2013 to May 2017 and underwent MRI in the early stage of AP. PVST was evaluated on the T1WI, T2WI fat-suppression, and dynamic-enhancement sequences. Evaluating the MR imaging, AP was graded as mild, moderate, and severe AP based on the MR severity index (MRSI) and was also classified into interstitial edematous AP and necrotizing AP. According to the New Revised Classification of AP 2012, AP in the clinic setting was graded as mild, moederately severeand severe AP. χ2 test or Fisher exact test calculated the differences of the prevalence of PVST in different severity and classification of AP, Mann-Whitney U test calculated the difference of hospitalization time between patients with PVST and those without PVST. Results Among the 396 patients with AP, PVST was detected in 30 patients (7.5％,30/396), it formed most frequently in splenic vein(73.3％, 22/30), followed by portal (30.0％, 9/30) and superior mesenteric(16.7％, 5/30) veins. According to MRSI, there were 205, 177, and 14 patients with mild, moderate, and severe AP, respectively;among mild, moderate, and severe AP, there were 2, 21, and 7 patients with PVST, respectively (χ2=41.455, P<0.01), there were also statistical differences in the prevalence of portal and splenic vein thrombosis (P<0.05), but there was no statistical difference in the prevalence of superior mesenteric vein thrombosis (P>0.05). Three hundred and eleven patients had interstitial edematous AP and 65 patients had necrotizing AP, among which there were 11 and 19 patients with PVST(χ2=48.447,P<0.01), the prevalence of portal, splenic and superior mesenteric vein thrombosis in necrotizing AP were all higher than that in interstitial edematous AP (P<0.05). Based on the New Revised Classification of AP 2012, there were 194, 184 and 18 patients with mild, moderately severe, and severe AP, respectively; among mild, moderately severe, and severe AP, there were 0, 25, and 5 patients with PVST, respectively (χ2=42.130, P<0.01), there was no statistical differences in the prevalence of portal, splenic and superior mesenteric vein thrombosis (P>0.05). Patients with PVST and those without PVST in the early AP, the hospitalization time [median (interquartile range)] were 18 (13 to 22) days and 13 (10 to 19) days (Z=-2.913, P=0.004). Conclusion PVST in early AP presented more frequently with the increase in severity of AP based on both the MRSI and Newly Revised Classification of AP 2012, along with longer duration ofhospitalization.