Objective:To investigate whether Lycopi Herba can serve as a viable alternative to Alismatis Rhizoma in the treatment of heart failure (HF) through network pharmacology and molecular docking techniques.Methods:TCMSP database was used to filter active components of Lycopi Herba and Alismatis Rhizoma. SwissTargetPrediction database was used to predict potential targets. HF-related targets were collected from databases such as GeneCards, OMIM, and DisGeNET. Venny 2.1.0 was used to draw a Venn diagram illustrating the intersection of targets between Lycopi Herba and Alismatis Rhizoma and HF. A protein-protein interaction (PPI) network was established using the String database, and key targets for the treatment of HF with Lycopi Herba and Alismatis Rhizoma were selected using Cytoscape 3.9.1 software to construct a component-intersection target network. The intersection targets were then analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using Metascape. Molecular docking techniques were used to evaluate the affinity between active components and key targets.Results:Lycopi Herba primarily targeted pivotal proteins such as HMGCR and CYP27B1, while Alismatis Rhizoma had a broader target spectrum, including PPARA, JAK2, among others. Shared key targets between the two included HMGCR and ESR1, which were primarily involved in cholesterol synthesis and steroid hormone biosynthesis. Enrichment pathway analysis showed similarities in steroid metabolism between the two; Alismatis Rhizoma, however, was more likely to act through protein phosphorylation regulation and modulating the PI3K-Akt signaling pathway for HF treatment. A unique target for Lycopi Herba in treating HF was CHRM4, indicating its potential for blood pressure regulation and myocardial protection.Conclusions:Both Lycopi Herba and Alismatis Rhizoma exhibit certain commonalities in the treatment of HF, but Alismatis Rhizoma has a wider range of targets and signaling pathways, implying more extensive therapeutic potential. However, considering the nephrotoxicity of Alismatis Rhizoma, Lycopi Herba could be considered as an alternative treatment for HF, especially in patients with renal insufficiency or in the early stages of HF.

ObjectiveTo retrospectively analyze the effect of modified Shugan Dingji Decoction （疏肝定悸汤） on the occurrence of endpoint events in patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation. MethodsA retrospective cohort study was conducted using the electronic medical record database of Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine to screen and include patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation from January 1st， 2018， to December 31th， 2021. The included patients were divided into an exposure group and a non-exposure group， each consisting of 100 cases， based on whether they received modified Shugan Dingji Decoction. General information of the patients including age， gender， body mass index， duration of illness and comorbidities， medication history， cardiac structure and function indicators such as left atrial diameter， left ventricular end-diastolic diameter， stroke volume and ejection fraction， and the occurrence of endpoint events assessed through 24-hour dynamic electrocardiography or electrocardiogram to determine the recurrence of paroxysmal atrial fibrillation were collected. Kaplan-Meier （K-M） curves and Log-Rank tests were used to conduct survival analysis on the occurrence of endpoint events in the two groups of patients. Univariate and multivariate Cox regression analyses were used to analyze the impact of various factors on entry into endpoint events. Additionally， a safety assessment was performed by comparing liver and kidney function indicators before and after treatment. ResultsIn the non-exposure group， a total of 49 cases （49.0%） experienced endpoint events， while in the exposure group， there were 26 cases （26.0%）. The Log-rank test indicated significant difference between the two groups （χ²=11.211， P=0.001）. Univariate Cox regression analysis showed that age， duration of illness， hypertension， diabetes， chronic heart failure， left atrial diameter， stroke volume， and the use of modified Shugan Dingji Decoction may be the influencing factors for the occurrence of endpoint events in patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation （P＜0.05 or P＜0.01）. Multivariate Cox regression analysis showed that the risk of endpoint events in the exposure group was significantly lower than that in the non-exposure group （P＜0.01）. Patients with a duration of illness ＞12 months had a significantly higher risk of endpoint events compared to those with a duration of illness ≤12 months （P＜0.01）. Patients without concomitant hypertension had a lower risk of endpoint events compared to those with hypertension （P＜0.05）. Patients with left atrial diameter ＞40 mm had significantly higher risk of endpoint events than those with left atrial diameter ≤40 mm （P＜0.01）. There was no statistically significant difference in liver and kidney function indicators between the two groups before and after treatment （P＞0.05）. ConclusionThe use of modified Shugan Dingji Decoction is a protective factor for patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation， which can help to reduce the recurrence and progression of atrial fibrillation. Long duration of illness， concomitant hypertension， and enlarged left atrial diameter are risk factors for patients to experience endpoint events.

Objective To evaluate the characteristics of a rat model of heart failure with a preserved ejection fraction(HFpEF)induced by combined factors,and to investigate the correlation of myocardial strain parameters to myocardial hypertrophy and fibrosis.Methods Eight WKY rats and eight spontaneously hypertensive rats(SHR)served as control groups and were fed normal feed until the end of the experiment.Thirty-two SHR rats were equally divided into SHR+S,SHR+F,SHR+SF,and SHR+Combined groups,and fed high-salt,high-fat,high-salt-fat,or high-salt-fat-sugar feed,respectively,in combination with intraperitoneal injection of streptozotocin for 30 weeks.After modeling,the heart weight/body weight(HW/BW)ratio,systolic blood pressure(SBP),and diastolic blood pressure(DBP)were measured.Echocardiography was performed to measure the left ventricular(LV)end-diastolic internal diameter(LVIDd),LV anterior wall thickness(LVAWd),LV posterior wall thickness(LVPWd),LV ejection fraction(LVEF),isovolumetric diastolic time(IVRT),and peak early diastolic passive filling velocity(E)/early diastolic mitral annular velocity(e').Speckle tracking echocardiography was conducted to determine the global longitudinal strain(GLS)and strain rate(GLSr),global radial strain(GRS)and strain rate(GRSr),as well as the global circumferential strain(GCS)and strain rate(GCSr).Serum was collected and analyzed for triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),glucose(GLU),and glycated serum protein(GSP).ELISA were used to measure serum B-type brain natriuretic peptide(BNP),angiotensin Ⅱ(AngⅡ),and galectin-3(Gal-3).Myocardial tissue was subjected to HE and Masson staining for cardiomyocytes and myocardial fibrosis,and the cardiomyocyte cross-sectional area(CSA)and collagen volume fraction(CVF)were calculated.Additionally,the correlation of myocardial strain parameters to CSA and CVF was analyzed.Results Compared with the control group,in model groups,especially the SHR+combined group,HW/BW,SBP,DBP,serum indexes(TC,TG,LDL-C,GLU,GSP,BNP,AngⅡ,and Gal-3)and echocardiographic parameters(LVIDd,LVAWd,LVPWd,IVRT,and E/e')were significantly up-regulated.Absolute values of speckle-tracking echocardiographic parameters(GLS,GLSr,GRS,GRSr,GCS,and GCSr)were decreased considerably.HE and Masson staining of myocardial tissues suggested marked cardiomyocyte hypertrophy and fibrosis,and significant increases were observed in CSA and CVF(P＜0.05).Correlation analysis showed that GLSr,GCS,and GCSr were strongly linked to CSA,and GLS,GLSr,and GCSr were strongly linked to CVF(P＜0.01).Conclusions A rat model of HFpEF induced by hypertension and dysregulation of glucolipid metabolism replicated the basic characteristics of HFpEF in terms of etiology,clinical features,and myocardial pathological changes,and might be a reliable animal model of metabolic syndrome-related HFpEF.Moreover,myocardial strain indices were closely related to myocardial hypertrophy and fibrosis and might indirectly reflect subtle myocardial lesions and dysfunction.

ObjectiveTo explore the material basis and molecular mechanism of Linggui Qihua prescription （LGQH） against myocardial fibrosis in heart failure with preserved ejection fraction （HFpEF）. MethodLiquid chromatography-mass spectrometry （LC-MS） was used to qualitatively analyze the active components of LGQH. AutoDock software was employed for molecular docking between the active components of LGQH and target proteins including α-smooth muscle actin （α-SMA）， type Ⅰ collagen （ColⅠ）， type Ⅲ collagen （ColⅢ）， matrix metalloproteinase-9 （MMP-9）， and tissue inhibitor of metalloproteinase-1 （TIMP-1）. In vivo experiments were conducted on 40 spontaneously hypertensive rats （SHRs） aged 4 weeks， which were divided into an HFpEF group， an Entresto group （0.018 g·kg^-1）， and low- and high-dose LGQH groups （3.87， 7.74 g·kg^-1）. A high-fat， high-salt， and high-sugar diet was administered for 16 weeks along with intraperitoneal injection of streptozotocin solution for 8 weeks to establish an HFpEF model in rats. The blank group consisted of 10 Wistar Kyoto （WKY） rats and 10 SHRs. After successful modeling， the WKY， SHR， and HFpEF groups were given equal volumes of normal saline， while the other three groups received predetermined interventions. Daily oral gavage was performed for 6 weeks. After intervention， echocardiography was conducted to measure left ventricular （LV） anterior wall thickness （LVAWd）， LV posterior wall thickness （LVPWd）， LV internal diameter at end-diastole （LVIDd）， LV ejection fraction （LVEF）， isovolumic relaxation time （IVRT）， early diastolic peak velocity of mitral valve inflow （E）， and early diastolic mitral annular velocity （e'）. The E/e' ratio was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum atrial natriuretic peptide （ANP）， B-type natriuretic peptide （BNP）， and galectin-3 （Gal-3）. Myocardial fibrosis was observed through Masson staining of pathological sections， and collagen volume fraction （CVF） and perivascular fibrosis ratio （PFR） were calculated. Real-time polymerase chain reaction （PCR） and Western blot were employed to detect LV myocardial mRNA and protein expression of α-SMA， ColⅠ， ColⅢ， MMP-9， and TIMP-1. ResultLC-MS identified 13 active components in LGQH. Molecular docking indicated stable binding of the 13 compounds with five target proteins. In vivo experiments showed that compared with the blank group， the HFpEF group had significantly increased LVAWd， LVPWd， LVIDd， IVRT， E/e'， ANP， BNP， Gal-3， CVF， and PFR. LV myocardial α-SMA， ColⅠ， and ColⅢ mRNA and protein expression was significantly upregulated， while MMP-9/TIMP-1 mRNA and protein ratios were significantly downregulated （P<0.05， P<0.01）. Compared with the HFpEF group， LGQH might dose-dependently reduce LVAWd， LVPWd， LVIDd， IVRT， E/e'， ANP， BNP， Gal-3， CVF， and PFR， downregulated myocardial α-SMA， ColⅠ， ColⅢ mRNA expression， α-SMA， and ColⅠ protein expression， and upregulated MMP-9/TIMP-1 mRNA and protein expression （P<0.05， P<0.01）. ConclusionLGQH contains multiple active components and may inhibit myocardial fibrosis in HFpEF rats. It may further alleviate LV hypertrophy， dilation， and diastolic dysfunction， making it an effective Chinese medicinal prescription for treating HFpEF.

ObjectiveTo analyze the pharmacodynamic material basis of Hippophae Folium in the treatment of hyperlipidemia by network pharmacology and experimental verification. MethodThe hyperlipidemic HepG2 cell model induced by oleic and palmitic acid （molar ratio 2∶1） was established. The optimal concentration of Hippophae Folium containing serum was determined by cell counting kit （CCK）-8 method. The cells were intervened by the medicated serum， and oil red O staining was used to determine the success of the model. The contents of total cholesterol （TC） and triglyceride （TG） were determined by enzyme-linked immunosorbent assay （ELISA）. The possible mechanism of action was analyzed by network pharmacology， and molecular docking was performed to detect the binding ability of the potential targets. ResultCCK-8 assay showed that 10% medicated serum was the optimal concentration for cell growth. Oil red O staining proved that the hyperlipidemic cell model induced by oleic and palmitic acid has been built. After treatment with medicated serum， the contents of TG and TC decreased， indicating that Hippophae Folium had a good therapeutic effect on hyperlipidemia. Network pharmacology revealed that the core targets of Hippophae Folium in the treatment of hyperlipidemia were albumin （ALB）， peroxisome proliferative activated receptor γ （PPARγ） and matrix metalloprotein（MMP）-9， involving 755 biological processes， 73 molecular functions and 3 cellular components. By Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis， it was found PPAR， hypoxia inducible factor（HIF）-1， AMP-activated protein kinase（AMPK） and other signal pathways were involved in the treatment of hyperlipidemia by Hippophae Folium. ConclusionHippophae Folium containing serum （10%） could reduce lipid accumulation and intracellular TG and TC levels in hyperlipidemic cell model， and its mechanism of action might be realized by activating PPAR signal pathway.

The study of distinct genes, chromosomes and the spatio-temporal relationships between them is of great significance in genetics, developmental biology and biomedicine. CRISPR/Cas9 has become the most widely used gene editing tool due to its excellent targeting ability. Recently, researchers have developed a series of advanced live cell imaging techniques based on the nuclease-inactivated mutant of Cas9 (dCas9), providing rapid and convenient tools for high-resolution imaging of specific sites in the chromatin and genome. This review summarizes the advances of CRISPR/dCas9 system in live cell imaging from three aspects, including the strategies of cell delivery, optimization of the fluorescence signals, as well as orthogonal and multicolor imaging. Furthermore, we shed light on the development trends and prospects of this field.
CRISPR-Cas Systems/genetics* ; Chromatin ; Endonucleases ; Gene Editing

Objective:To evaluate the clinical value of ultrasound attenuation parameters (UAP) in diagnosing the liver steatosis degree in patients with chronic liver disease, and to explore the relevant factors that affect UAP detection values.Methods:130 cases with chronic liver disease diagnosed as liver steatosis by liver biopsy during January 2014 to May 2019 were selected from the Hepatology Department of Integrated Traditional Chinese and Western Medicine of the Third Hospital of Hebei Medical University. UAP and liver stiffness (LSM) were detected by iLivTouch, and the body mass index (BMI) was calculated. Simultaneously, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), total bilirubin (TBil), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL) levels and peripheral platelet (PLT) counts were measured. The correlation between UAP and liver steatosis was analyzed based on the liver histopathological results. SPSS 21.0 statistical software was used for statistical analysis. Receiver operating characteristic curve (ROC) was used to analyze the accuracy and specificity of UAP in the diagnosis of liver steatosis in patients with chronic liver disease. Spearman’s rank correlation analysis was used to study the relevant factors affecting UAP value.Results:The histopathological changes of liver biopsy showed that there were 43 cases of grade F1, 47 cases of F2, 32 cases of F3 and 8 cases of F4. UAP and BMI ( r = 0.363, P < 0.001), and UAP and liver steatosis degree ( r = 0.380, P < 0.001) were positively correlated. BMI and the liver steatosis degree were independent predictors of UAP value. The cut-off points for UAP to diagnose liver steatosis degree were 276 dB/m for F≥2, 288 dB/m for F≥2, 293 dB/m for F≥3, and F = 4, respectively. The sensitivity and specificity was 0.379, 0.500, 0.750, and 0.930, 0.922, 0.836, respectively. Conclusion:Ultrasonic attenuation parameters cannot only determine the presence or absence of liver steatosis in patients with chronic liver disease, but also can better assess the liver steatosis degree.

Objective To explore the prevalence and epidemic characteristics of overweight, obesity, and central obesity in Shanghai Pudong New Area. Methods Multi-stage stratified random sampling method was conducted in Pudong New Area in 2013. Residents over 15 years old were randomly selected from 13 communities and participated in the cross-sectional study. A structured questionnaire was used to collect the information and physical examination, biochemical assays were also conducted. SPSS 20. 0 was used to analyze the results. Results The averagebodymassindexofparticipantswas(25.04±3.79)kg/m2andtheaveragewaistcircumferencewas(82.44± 9. 51) cm. The prevalences of overweight, obesity, and central obesity were 41. 67%, 17. 70%, and 31. 32%respectively. Standardized prevalences of overweight, obesity, and central obesity were 34. 39%, 16. 96%, and 25. 66% respectively, according to 2010 national age composition of population. Statistically significant sex differences were found among the prevalence of overweight, obesity, and central obesity groups(all P<0. 05). The prevalence of central obesity in female was raised by increasing age. Residents with hypertension, hyperglycemia, dyslipidemia, and metabolic disorders had higher prevalences in overweight, obesity, and central obesity ( all P<0. 05). Conclusion The prevalences of overweight, obesity, and central obesity among the residents in Shanghai Pudong New Area were relatively high. Relevant risk factors should be explored to promote health education that may enhance people′s awareness of weight management.