Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

There is a bidirectional relationship between intestinal flora and bile acids,and the imbalance of intestinal flora-bile acid axis metabolism is closely related to hypertension.Based on classical TCM literature and clinical practice,this article found that"earth deficiency"is the important pathological basis of hypertension,"wood depression"is the initiating factor of hypertension,and"earth deficiency and wood depression"is the key pathogenesis of hypertension.Combined with the research results of modern medicine and molecular biology,it is considered that the imbalance of intestinal flora and abnormal bile acid metabolism are closely related to the"earth deficiency"and"wood depression"of TCM respectively,and the imbalance of intestinal flora-bile acid axis coincides with the"earth deficiency and wood depression"of TCM in the process of hypertension.It is of great theoretical and practical significance to explore the biological connotation of hypertension"earth deficiency and wood depression"from the perspective of intestinal flora-bile acid axis for guiding TCM to prevent and treat hypertension.

ObjectiveTo observe the effect of Zhengan Xifengtang on blood pressure and fecal microflora of spontaneously hypertensive rats （SHRs）. MethodA total of 75 male SHRs aged nine weeks were randomly divided into SHR group， Benazepril group （1.00 mg·kg^-1·d^-1）， high-dose Zhengan Xifengtang group （34.5 g·kg^-1·d^-1）， medium-dose Zhengan Xifengtang group （17.25 g·kg^-1·d^-1）， and low-dose Zhengan Xifengtang group （8.625 g·kg^-1·d^-1）. A total of 15 male Wistar-Kyoto （WKY） rats aged nine weeks were selected as the normal group. The normal group and SHR group were administrated with an equal volume of distilled water for eight weeks. During the administration， the blood pressure of the rats was measured regularly. After the intervention， fresh feces were collected with a sterile frozen storage tube， and 16S amplicon information was collected and analyzed. Plasma， hippocampus， and ileum of rats were collected for ultra-high performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS） detection. ResultZhengan Xifengtang decreased the systolic blood pressure and diastolic blood pressure of SHRs. Compared with the SHR group， Zhengan Xifengtang decreased the diversity of fecal microflora of SHRs. At the phylum level， Zhengan Xifengtang increased the relative abundance of SHR Verrucomicrobia and Actinobacteria and decreased the relative abundance of Synergistetes， Tenericutes， and Candidatus Saccharibacteria. Compared with the SHR group， Zhengan Xifengtang increased the relative abundance of Blautia wexlerae， Fusicatenibacter saccharivorans， and Akkermansia muciniphila and decreased the relative abundance of Clostridium lavalense， Intestinimonas butyriciproducens， Acetatifactor muris， Alloprevotella rava， and Oscillibacter valericigenes. Spearman correlation analysis showed that the systolic blood pressure of rats was negatively correlated with the relative abundance of Ethanoligenens， Aerococcus， Butyrivibrio， Olsenella， Bifidobacterium， Clostridium XIVb， Allobaculum， and Fusicatenibacter and positively correlated with the relative abundance of Alloprevotella. Zhengan Xifengtang increased the contents of plasma， hippocampal 5-hydroxy tryptamine（5-HT）， and 5-hydroxyindole acetic acid（5-HIAA） in SHRs and decreased the contents of 5-HT and 5-HIAA in the ileum， and the content of 5-HT in the hippocampus was negatively correlated with that in the ileum. ConclusionZhengan Xifengtang can reduce the blood pressure of SHRs， which may be related to reducing the diversity of SHR microflora， regulating the structure of the microflora， increasing the relative abundance of 5-HT and short-chain fatty acids bacteria， and lowering the relative abundance of pathogenic bacteria related to intestinal inflammation.

The appetite regulation system is important for improving metabolism,regulating energy,and maintaining body weight by promoting/inhibiting appetite neurons/factors.Recent studies have shown that the appetite reg-ulation system can directly affect various hypertension-related pathophysiological processes,including sympathetic excita-tion,water and sodium retention,vascular damage,and oxidative stress.This review summarizes the roles of central appe-tite neurons,central appetite factors,and peripheral appetite factors in the pathogenesis of hypertension.

Metabolic regulation has been proven to play a critical role in T cell antitumor immunity. However, cholesterol metabolism as a key component of this regulation remains largely unexplored. Herein, we found that the low-density lipoprotein receptor (LDLR), which has been previously identified as a transporter for cholesterol, plays a pivotal role in regulating CD8

Objective To study the effect of masked hypertension (MH) and white coat hypertension (WCH) on vascular elasticity and endothelial function in elderly patients.Methods Four hundred and eighty-seven elderly patients who underwent physical examination in our our hospital were divided into normotension group (n=128),WCH group (n=115),MH group (n=112) and hypertension group (n=132) according to their diagnostic office blood pressure and 24 h ambulatory blood pressure.The brachial artery FMD,serum NO and endothelin-1 (ET-1) levels,and cfPWV were measured.Results The FMD and serum NO level were significantly lower while the serum ET-1 level and cfPWV were significantly higher in WCH group,MH group and hypertension group than in normotension group (P＜0.05).The FMD and serum NO level were significantly higher while the serum ET-1 and cfPWV were significantly lower in WCH group and MH group than in hypertension group (P＜ 0.05).Multivariate linear stepwise regression analysis showed that WCH,MH and hypertension were the independent influencing factors for FMD,serum NO and ET-1 level and cfPWV with normotension used as reference after adjustment of confounding factors (P＜0.01).Conclusion MH and WCH are the risk factors for the decreased vascular elasticity and endothelial dysfunction in elderly patients.

Objective To study the effect of empty-nest (EN) on the variability of HBPV in elderly hypertensive patients.Methods 457 elderly essential hypertensive patients admitted to our hospi tal were divided into non EN group (A group,n =183),EN couple group (B group,n =150),and EN single group (C group,n=124).They underwent 7-day HBPV,their BPV was detected,their loneliness and depressive symptoms were assessed according to the UCLA-LS and GDS.Results The variability of self-measured DPB and SBP,UCLA-LS and GDS score were significantly higher in B and C groups than in A group (P＜0.05).The variability of SBP,UCLA-LS and GDS score were significantly higher in C group than in B group (46.06±7.98 vs 38.95±8.11;7.67±2.58 vs 6.48±2.60,P＜0.05).Partial correlation analysis showed that the variability of SBP and DBP was positively related with the UCLA-LS and GDS score (P＜0.05).The variability of SBP was significantly higher in B and C groups than in A group after adjustment of confounding factors (P=0.000).Conclusion EN,an independent influencing factor for the variability of blood pressure in elderly hypertensive patients,is related with their loneliness and depression.

Objective To study the effect of telmisartan combined with rosuvastatin on white matter lesion (WML) in elderly hypertensive patients.Metheds Three hundred and twenty-nine elderly patients with mild-moderate essential hypertension (EH) were divided into control group (n=167) and combined treatment group (n=162).The patients in control group were treated with telmisartan (40 mg/d) and those in combined treatment group were treated with telmisartan plus rosuvastatin (10 mg/d).Their white matter hyperintensivity (WMH),periventricular white matter hyperintensity (PWMH),and deep white matter hyperintensity (DWMH) were measured by head MRI.Results The total WMH,PWMH and DWMH were significantly higher in two groups in the third and fifth years than at the baseline (P＜0.05).The growth rate of total WMH,PWMH and DWMH was significantly lower in combined treatment group than in control group in the third and fifth years (P＜0.05).Conclusion Telmisartan combined with rosuvastatin plays an important role in stablizing blood pressure,regulating blood lipids,and delaying WML.

Objective To study the association between morning surge (MS) of systolic blood pressure (SBP) and white matter lesions in elderly essential hypertensive (EH) patients.Methods Three hundred and thirty-seven elderly EH patients from Zhangqiu of Shandong Province were divided into MS group (n=150) and non-MS group (n=187).Their 24 h ambulatory SBP was monitored.Their white matter hyperintensity (WMH) was assessed according to their brain MRI.Results The total WMH,periventricular WMH,and deep WMH were significantly higher in MS group than in non-MS group (P＜0.01).The MS of SBP was positively related with the total WMH,periventricular WMH,and deep WMH (r=0.561,r=0.563,r=0.283,P＜0.01),and was an independent risk factor for total WMH,periventricular WMH,and deep WMH after adjustment for confunders (r=0.479,r=0.486,r=0.208,P＜0.01).Conclusion MS of SBP is an independently risk factor for WMH in elderly EH patients.