Epimedin B(EB)is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim.,a traditional herb widely used in China.Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase(TYR).However,the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear.Herein,as an extension to our previous investi-gation,we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and eluci-date the melanogenesis mechanism by assessing its effects on the TYR family of proteins(TYRs)in terms of expression,activity,and stability.The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt(referred to as protein kinase B(PKB))/glycogen synthase kinase 3β(GSK3β)/β-catenin,p-p70 S6 kinase cascades,and protein 38(p38)/mitogen-activated protein(MAP)kinase(MAPK)and extracellular regulated protein kinases(ERK)/MAPK pathways,after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues.Furthermore,EB exerted repigmentation by stimulating TYR activity in hydroquinone-and N-phenylthiourea-induced TYR inhibitive models,including melanoma cells,zebrafish,and mice.Finally,EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding,TYR-related protein 1 formation,and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes.These data conclude that EB can target TYRs and alter their expression,activity,and stability,thus stimulating their pigmentation function,which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.

Evaluating the consistency of herb injectable formulations could improve their product quality and clinical safety, particularly concerning the composition and content levels of trace ingredients. Panax notoginseng Saponins Injection (PNSI), widely used in China for treating acute cardiovascular diseases, contains low-abundance (10%-25%) and trace saponins in addition to its five main constituents (notoginsenoside R₁, ginsenoside Rg₁, ginsenoside Re, ginsenoside Rb₁, and ginsenoside Rd). This study aimed to establish a robust analytical method and assess the variability in trace saponin levels within PNSI from different vendors and formulation types. To achieve this, a liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method employing multiple ions monitoring (MIM) was developed. A "post-column valve switching" strategy was implemented to eliminate highly abundant peaks (NR₁, Rg₁, and Re) at 26 min. A total of 51 saponins in PNSI were quantified or relatively quantified using 18 saponin standards, with digoxin as the internal standard. This study evaluated 119 batches of PNSI from seven vendors, revealing significant variability in trace saponin levels among different vendors and formulation types. These findings highlight the importance of consistent content in low-abundance and trace saponins to ensure product control and clinical safety. Standardization of these ingredients is crucial for maintaining the quality and effectiveness of PNSI in treating acute cardiovascular diseases.
Ginsenosides ; Saponins ; Chemometrics ; Panax notoginseng ; Cardiovascular Diseases ; Chromatography, Liquid ; Tandem Mass Spectrometry

The current status and major problems of doctors' working ability archives were investigated.The qualitative interview method was used to explore the establishment of doctors' working ability archives for secondary,tertiary hospitals and community health service centers,as well as for doctors of Chinese and Western medicine.The collection cycle of relevant data and measures to improve accuracy,application value and response were also explored.The aim of establishing the archives of doctors' working ability is to provide reference for evaluation of clinicians accurately,developing a rational incentive system,improving data support and upgrading hospital management level.

Objective To explore the correlation between the self-management and self-efficacy of senile patients with chronic heart failure (CHF). Methods In this study, the conveninent sampling method was adopted. From June to December 2016, totally 416 senile CHF patients hospitalized in the Department of Cardiology of 5 general class Ⅲ grade A hospitals in Xi'an were investigated with the general demographic data questionnaire, self-management scale for CHF patients and chronic disease self-efficacy scale. Results The score of self-management in the senile CHF patients in Xi'an totaled (50.76±9.98), with a scoring rate of 63.5%; the scores of medication management, food and beverage management, psychological and social management and symptom management were (13.38±3.38), (7.89±2.14), (12.81±2.91) and (16.69±4.26), with the scoring rates of 66.9%, 65.8%, 64.1% and 59.6%, respectively, showing a medium level; and there was statistically significant difference in the total self-management score between patients with different marital status, per capita income and heart function grading (t=-2.443, 10.906, 16.229;P<0.05). The score of self-efficacy totaled (34.30±11.90), with a scoring rate of 57.17%, showing a medium level. The correlation analysis showed that there was a positive correlation between self-efficacy and self-management (r=0.161, P< 0.05). Conclusions The self-management and self-efficacy of the senile CHF patients in Xi'an remain at a medium level, which could be possibly improved, and the two are closely correlated. The results suggest that we should pay more attention to the patient's management confidence in the disease itself, attach importance to their psychological and social support and enhance their self-efficacy, thus improving their self-management. This is of great significance in controlling CHF and improving the patient's quality of life.

Objective To investigate the pharmacological effect and mechanism of mouse intermedin (IMD)for antagonizing cardiac hypertrophy by using isoproterenol (ISO)induced mouse cardiomegaly model.Methods The mouse cardiomegaly model was constructed by small dose of ISO subcutaneous injection.The mouse blood dynamic indexes and heart weight/body weight rati-o were investigated.Then the cardiomyocyte cross-sectional area,apoptosis and cardiac tissue fibrosis were evaluated by using the cardiac tissue section.ANP,BNP,mRNA expression levels of endogenous IMD and its receptors system in cardiac tissues were de-tected by using real time fluorescence PCR method.Results Compared with the ISO induced mouse cardomegaly model group,the intraperitoneal injection of IMD significantly decreased the heart weight/body weight ratio and cardiomyocyte cross-sectional area increased by ISO treatment,cardiomegaly marker ANP and BNP mRNA level,cardiomyocyte apoptosis and cardiomyocyte fibrosis, improved the cardiac function,left ventricular pressure,maximal and minimal rate of LV pressure increase and decrease during the isovolumetric contraction phase,stroke volume,cardiac output and ejection fraction,but significantly decreased the left ventricle end-diastolic pressure.In addition,the ISO treatment significantly induced the expressions of endogenous IMD and its receptors in heart tissues.Conclusion ISO induces the expressions of endogenous IMD and its receptors in cardiac tissues,and exogenous IMD sup-plementation therapy realizes the pharmacological protective effect for antagonizing cardiomegaly by ISO activated IMD receptor system.

Objective To explore the clinicopathological characters of T2 gastric cancer and the value of MSCT in the preop‐erative TNM staging of T2 gastric cancer .Methods A total of 93 patients with T2 gastric cancer were included in our study and un‐derwent preoperative MSCT staging ,who were confirmed by pathologic results .Then the results were compared with those of path‐ologic TNM staging .Also the clinicopathological features of the T2 gastric cancer were analyzed .Results There were no statistical‐ly significant differences in the clinicopathological characters among T2a and T2b patients (P>0 .05) .Comparing with pathologic TNM stage ,the T staging accuracy of MSCT was 91 .40% (85/93) ,the N staging accuracies of CT was 66 .67% (62/93) ,in which , 68 .18% (30/44) ,65 .00% (26/40) ,60 .00% (3/5) and 75 .00% (3/4) were for pN0 ,pN1 ,pN2 and pN3 .And the TNM staging ac‐curacies of CT was 67 .74% (63/93) ,in which ,68 .18% (30/44) ,64 .10% (25/39) ,60 .00% (3/5) and 100% (5/5) were for stageⅠ ,Ⅱ ,Ⅲ and Ⅳ .Conclusion There are no significant different on clinicopathology features among T2a and T2b patients .MSCT can clearly determine the preoperative TNM staging of T2 gastric cancer .

Objective:To study the changes and significance of Th17 and Treg cells as well as their associated cytokines in pe-ripheral blood of patients with chronic hepatitis C and cirrhosis in order to investigate their role in the pathogenesis of chronic hepatitis C and hepatitis C cirrhosis. Methods:Flow cytometry and ELSIA assay were used to detect the expression ratio of Th17 and Treg cells and the serum levels of IL-10,TGF-β,IL-6 and IL-17 in peripheral blood of healthy human and patients with chronic hepatitis C and hepatitis C cirrhosis. Than we analyzed the differences of the above detection index between the healthy and patients with chronic hepatitis C and hepatitis C cirrhosis. Results:The expression ratio of Th17 cells (1. 33%±0. 30%) in peripheral blood of patients with chronic hepatitis C and IL-6[(8. 10±2. 42)ng/L] and IL-17[(16. 70±4. 73)ng/L] serum levels were significantly higher than those in the healthy (Th17:1. 14%±0. 19%) and IL-6[(1. 72±6. 70)ng/L],IL-17[(12. 29±1. 88)ng/L],P<0. 05;The expression ratio of Treg cells in peripheral blood of patients with hepatitis C cirrhosis and chronic hepatitis C patients was significantly higher than that in the healthy (6. 21%±0. 76%,5. 89%±0. 85% vs 5. 51%±0. 59% ),P<0. 05,The ratio of Th17/Treg in patients with cirrhosis was significantly lower than that in patients with chronic hepatitis C and the healthy(0. 19±0. 02 vs 0. 22±0. 03,0. 21±0. 03),P<0. 05;the levels of IL-1[(16. 21±3. 76)ng/L] and TGF-β[(5. 15±0. 83)ng/L] in peripheral blood of patients with hepatitis C cirrhosis were significantly higher than those in chronic hepatitis C[(14. 36±2. 78)ng/L;(4. 47±0. 87)ng/L] and the healthy[(14. 01±3. 01)ng/L;(4. 43±0. 98)ng/L)],P<0. 05. Conclusion:Th17 and Treg cells and their related cytokines involved in the process of chronicity of hepatitis C and cirrhosis,Th17 and Treg cells and their related cytokines in the treatment and prevention of chronicity of hepatitis C and cirrhosis may have important significance.

To effectively screen treating pigmentation disorders drug, a new transgenic zebrafish drug screening model was constructed. Green fluorescent protein(GFP)were drived by tyrosinase-related protein 1a (tyrp1a)promoter specific expression in melanocyte. Effect of N-Phenylthiourea(PTU)and alpha-melanaocyte stimulating hormone(α-MSH)on the GFP expression and melanogenic of tyrp1a: eGFP zebrafish were photographed under the steromicroscope. Results showed that PTU could significantly inhibit the melanogenic and expression of GFP of zebrafish. As compared with control group, α-MSH treatment resulted in marked stimulation of body pigmentation and expression of GFP. In conclusion, a new transgenic zebrafish drug screening model was successfully established, which can be used for treating pigmentation disorders.

In recent years,a considerable number of epidemiological investigations and animal studies have confirmed that metabolic diseases, such as obesity,type 2 diabetes mellitus and metabolic syndrome, have adverse effects on brain functions,inducing mood disorders and cognition impairment. Brain dysfunctions induced by obesity and related complications are associated with numerous central abnormalities,involving brain shrinkage and neurotrophic function impairment,brain insulin resistance, brain oxidative stress,and brain leptin resistance,as well as dysfunctioned dopamine motivation and the reward system. Moreover,these brain dysfunctions are mediated by several peripheral factors, such as triglycerides/free fatty acids,proinflammatory cytokines,and corticosterone/glucocorticoid. On the other hand,metabolic disturbances correlated with emotional-cognitive disorders are evident,but the mechanisms remain obscure. Because of the drawbacks of animal models, the majority of researches focus on the impact of mental stress on the metabolism of lipid and glucose. The interrela?tionship between metabolic diseases and brain functions has become one of the hot spots for research. In this review,we mainly discussed the potential mechanisms underlying mood disorders and cognition impairment induced by obesity and related complications.

AIM:To study the expression of Jagged 2/Notch3 signaling molecules in pulmonary vascular wall of pulmonary hypertensive rats induced by monocrotaline .METHODS: SD rats were randomly divided into normal control group (C group,n=15), solvent control group (S group,n=15) and monocrotaline model groups (M group,n=15).The model of pulmonary hypertension was established by a single subcutaneous injection of monocrotaline (50 mg/kg).The rats in S group were given a single subcutaneous injection of the same dose of solvent .After 4 weeks, the pulmonary vascular remodeling was assessed by HE staining , and the mean pulmonary artery pressure ( mPAP) and right ventricular systolic pressure (RVSP) were determined by right heart catheterization .The expression of Jagged2/Notch3 /Hes5 molecules in the pulmonary vascular wall was detected by immunohistochemical method and real -time PCR.RESULTS:Compared with S group and C group , the percentage of medial wall thickness of smaller arteries in model group increased significantly (P<0.01).The levels of mPAP and RVSP in M group were significantly higher than those in S group and C groups (P<0.01).The results of real-time PCR showed that the expression of Jagged 2, Notch3 and Hes5 was significantly increased in M group compared with S group and C group .The data from immunohistochemical detection indicated that Jagged 2 mainly expressed in the intima of small lung artery , Notch3 and Hes5 mainly expressed in the medial smooth muscle cells .Com-pared with S group and C group , the expression of Jagged 2 and Notch3 was significantly increased in the lung small arteries of M group.CONCLUSION:The activation of Jagged2/Notch3 signaling pathway might play an important role in the for-mation of pulmonary hypertension .