Hydrolysis-Induced Cu2O Networks and the Triggered Peroxidase-Mimic Activity by Cr6+ under Neutral Conditions.

The current small-scale synthesis and relatively large size of Cu2O have limited its practical applications. Herein, we developed a hydrolysis strategy to prepare phase-pure Cu2O networks composed of small granules (ca. 25 nm) on a gram scale. The preparation involves in situ hydrolyzing the Hx[CuxCl2x] complexes prereduced in N,N'-dimethylformamide (DMF). The DMF-soluble Hx[CuxCl2x] complexes are critical for the homogeneous nucleation of CuCl seeds and subsequent hydrolysis, allowing for separate control over the nucleation and growth stages to regulate the formation of Cu2O networks. The novel Cu2O networks possess numerous exposed active sites and hierarchical porosities, conferring high catalytic activity and fast mass transfer capability. The inherent peroxidase-mimic activity of Cu2O is severely inhibited under neutral conditions but can be triggered by Cr6+, enabling the colorimetric assay of Cr6+ with the assistance of the oxidation-induced color change of 3,3',5,5'-tetramethylbenzidine. Through density functional theory calculation, we confirmed that the attachment of Cr6+ on the Cu2O surface reduced the dissociation energy of H2O2, enhancing the enzyme-mimic activity. The colorimetric detection method demonstrated a sensitive and specific assay capability for Cr6+ (LOD = 0.095 µM). Our work offers a straightforward protocol for novel design of metal or metal-based nanomaterials for nanozymes or other applications.

A PEG-assisted membrane coating to prepare biomimetic mesoporous silicon for PET/CT imaging of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) diagnosis remains challenging without expressing critical receptors. Cancer cell membrane (CCm) coating has been extensively studied for targeted cancer diagnostics due to attractive features such as good biocompatibility and homotypic tumor-targeting. However, the present study found that widely used CCm coating approaches, such as extrusion, were not applicable for functionalizing irregularly shaped nanoparticles (NPs), such as porous silicon (PSi). To tackle this challenge, we proposed a novel approach that employs polyethylene glycol (PEG)-assisted membrane coating, wherein PEG and CCm are respectively functionalized on PSi NPs through chemical conjugation and physical absorption. Meanwhile, the PSi NPs were grafted with the bisphosphonate (BP) molecules for radiolabeling. Thanks to the good chelating ability of BP and homotypic tumor targeting of cancer CCm coating, a novel PSi-based contrast agent (CCm-PEG-89Zr-BP-PSi) was developed for targeted positron emission tomography (PET)/computed tomography (CT) imaging of TNBC. The novel imaging agent showed good radiochemical purity (∼99 %) and stability (∼95 % in PBS and ∼99 % in cell medium after 48 h). Furthermore, the CCm-PEG-89Zr-BP-PSi NPs had efficient homotypic targeting ability in vitro and in vivo for TNBC. These findings demonstrate a versatile biomimetic coating method to prepare novel NPs for tumor-targeted diagnosis.

Photo-induced valence tautomerism and polarization switching in mononuclear cobalt complexes with an enantiopure chiral ligand.

Light-induced polarization switchable molecular materials have attracted attention for decades owing to their potential remote manipulation and ultrafast responsiveness. Here we report a valence tautomeric (VT) complex with an enantiopure chiral ligand. By a suitable choice of counter anions, a significant improvement in photoconversion has been demonstrated, leading to novel photo-responsive polarization switching materials.

Reappraisals of biological behaviors of PDGFRA mutant gastrointestinal stromal tumor / 中华病理学杂志

Objective: To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification. Methods: A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically. Results: There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant (P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference (P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant (P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant (P<0.001). Conclusions: GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.

Electrically Detectable Photoinduced Polarization Switching in a Molecular Prussian Blue Analogue.

Light, a nondestructive and remotely controllable external stimulus, effectively triggers a variety of electron-transfer phenomena in metal complexes. One prime example includes using light in molecular cyanide-bridged [FeCo] bimetallic Prussian blue analogues, where it switches the system between the electron-transferred metastable state and the system's ground state. If this process is coupled to a ferroelectric-type phase transition, the generation and disappearance of macroscopic polarization, entirely under light control, become possible. In this research, we successfully executed a nonpolar-to-polar phase transition in a trinuclear cyanide-bridged [Fe2Co] complex crystal via directional electron transfer. Intriguingly, by exposing the crystal to the wavelength of light─785 nm─without any electric field─we can drive this ferroelectric phase transition to completely depolarize the crystal, during which a measurable electric current response can be detected. These discoveries signify an important step toward the realization of fully light-controlled ferroelectric memory devices.

The Predictors and Outcomes of Functional Mitral Stenosis following Surgical Mitral Valve Repair: A Retrospective Analysis.

To optimize mitral valve repair outcomes, it is crucial to comprehend the predictors of functional mitral valve stenosis (FMS), to enhance preoperative assessments, and to adapt intraoperative treatment strategies. This study aimed to identify FMS risk factors, contributing valuable insights for refining surgical techniques. Among 228 selected patients, 215 underwent postoperative echocardiography follow-ups, and 36 met the FMS criteria based on a mean trans-mitral pressure gradient of >5 mmHg. Patients with FMS exhibited higher pulmonary systolic arterial pressure and increased late mortality during the follow-up. Univariable logistic regression analysis identified several risk factors for FMS, including end-stage renal disease, anterior leaflet lesion, concomitant aortic valve replacement, smaller ring size, ring type, and neochordae implantation. Conversely, resection alone and resection combined with neochordae implantation had protective effects against FMS. Multivariable logistic regression analysis revealed that smaller ring sizes and patch repair independently predicted FMS. When focusing on degenerative mitral regurgitation, the neochordae implantation without resection in leaflet repair, emerged as an independent predictor of FMS. Surgeons should weigh the substantial impact of surgical procedures on postoperative trans-mitral pressure gradients, emphasizing preoperative evaluation and techniques such as precise ring size assessment and effective leaflet management.

Blood pressure levels within normotensive range are independently associated with increased risk of arterial stiffness in adults without hypertension or prehypertension.

BACKGROUND AND AIMS: High blood pressure (BP) indices, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP) predict cardiovascular diseases and mortality. However, the association of these BP indices with arterial stiffness (AS) in the normotensive population (BP < 120/80 mmHg) remains unclear. METHODS AND RESULTS: Study participants who underwent health checkups at a tertiary referred center were recruited between November 2018 to December 2019. 2129 participants were enrolled after excluding those aged <18 years old, with elevated BP, history of hypertension, cardiovascular disease, and stroke, or with incomplete data. The brachial-ankle pulse wave velocity (baPWV) values were examined for evaluation of AS. Participants with higher blood pressure indices had significantly higher baPWV. Multiple linear regression revealed that all BP indices were positively associated with baPWV. According to the binary logistic regression analysis, participants in the higher SBP and MAP quartiles were significantly related to AS. The odds ratio (OR) for SBP Q2, Q3 and Q4 vs. Q1 were 6.06, 10.06 and 17.78 whereas the OR for MAP Q2, Q3 and Q4 vs. Q1 were: 5.07, 5.28 and 10.34. For DBP and PP, only participants belonging to the highest quartile were associated with AS(OR for DBP Q4 vs. Q1: 2.51; PP Q4 vs Q1: 1.94). CONCLUSIONS: BP indices were linearly related to the baPWV. Normotensive participants with higher quartiles of SBP, DBP, MAP, and PP, remained associated with increased AS. The SBP and MAP levels exhibited a more prominent relationship with AS.

Biomimetic Inorganic Nanovectors as Tumor-Targeting Theranostic Platform against Triple-Negative Breast Cancer.

Mesoporous silicon nanoparticles (PSi NPs) are promising platforms of nanomedicine because of their good compatibility, high payload capacities of anticancer drugs, and easy chemical modification. Here, PSi surfaces were functionalized with bisphosphonates (BP) for radiolabeling, loaded with doxorubicin (DOX) for chemotherapy, and the NPs were coated with cancer cell membrane (CCm) for homotypic cancer targeting. To enhance the CCm coating, the NP surfaces were covered with polyethylene glycol prior to the CCm coating. The effects of the BP amount and pH conditions on the radiolabeling efficacy were studied. The maximum BP was (2.27 wt%) on the PSi surfaces, and higher radiochemical yields were obtained for 99mTc (97% ± 2%) and 68Ga (94.6% ± 0.2%) under optimized pH conditions (pH = 5). The biomimetic NPs exhibited a good radiochemical and colloidal stability in phosphate-buffered saline and cell medium. In vitro studies demonstrated that the biomimetic NPs exhibited an enhanced cellular uptake and increased delivery of DOX to cancer cells, resulting in better chemotherapy than free DOX or pure NPs. Altogether, these findings indicate the potential of the developed platform for cancer treatment and diagnosis.

Magnetoelectricity Enhanced by Electron Redistribution in a Spin Crossover [FeCo] Complex.

Molecular-based magnetoelectric materials are among the most promising materials for next-generation magnetoelectric memory devices. However, practical application of existing molecular systems has proven difficult largely because the polarization change is far lower than the practical threshold of the ME memory devices. Herein, we successfully obtained an [FeCo] dinuclear complex that exhibits a magnetic field-induced spin crossover process, resulting in a significant polarization change of 0.45 µC cm-2. Mössbauer spectroscopy and theoretical calculations suggest that the asymmetric structural change, coupled with electron redistribution, leads to the observed polarization change. Our approach provides a new strategy toward rationally enhancing the polarization change.

Nephrolithiasis is associated with the severity of coronary artery calcification, but not with coronary artery stenosis.

PURPOSE: Emerging data have indicated that nephrolithiasis is possibly associated with subclinical coronary artery disease (CAD). Considering that a significant proportion of obstructive CAD in non-elderly individuals occurs in those without detectable calcium score (CACS), this study aimed to investigate whether nephrolithiasis is still associated with CAD as assessed by coronary computed tomography (CT)-derived luminal stenosis [using Gensini score (GS)]. METHODS: A total of 1170 asymptomatic adults without known CAD who underwent health examinations were recruited. Nephrolithiasis was assessed using abdominal ultrasonography (US). Individuals with a self-reported stone history, but no evidence of nephrolithiasis were excluded. The CACS and GS were measured using 256-slice coronary CT. RESULTS: Nearly half of these patients had a CACS > 0 (48.1%), and a higher prevalence of nephrolithiasis was observed than in those who had zero CACS (13.1% vs. 9.7%). However, no significant intergroup difference in GS was detected. A greater proportion of stone formers than non-stone formers had a higher risk category, whereas no significant difference was noted in Gensini category. Multiple linear regression analyses showed that the CACS independently predicted the presence of nephrolithiasis after adjustment. Importantly, we found that stone formers had a nearly threefold higher risk than non-stone formers of developing severe coronary calcification (CAC > 400). CONCLUSIONS: Nephrolithiasis was significantly associated with coronary artery calcification presence and severity, but not coronary luminal stenosis in patients without known CAD. Accordingly, the relationship between stone disease and CAD remains controversial, and additional studies are imperative to validate these findings.

Clinical characteristics and treatment outcomes of 68 patients with spontaneous iliac vein rupture: A case report and systematic review.

Objective: Spontaneous iliac vein rupture (SIVR) is a rare but life-threatening condition with limited understanding regarding its clinical presentation, pathogenesis, diagnosis, management, and risk factors for mortality. This study aims to address this gap by providing comprehensive insights into SIVR through personal case reports and a systematic review of previous cases. Methods: We detail a case of right SIVR caused by inappropriate positioning of the stent in the inferior vena cava and systematically reviewed previous cases. Logistic regression analysis was used to identify risk factors for mortality. Results: Our SIVR case was successfully managed with percutaneous mechanical thrombectomy and covered stent placement. In the systematic review, 68 patients were included in the analysis with an average age of 62.01 ± 13.25 years; 86.76% were female, 91.17% had left iliac vein rupture, 55.88% presented hemodynamic instability, 76.47% had lower abdomen or iliac fossa pain, 67.64% had deep venous thrombosis (DVT), and 32.35% had May‒Thurner syndrome (MTS). The mortality rates of conservative treatment and open surgery were 2.94% and 17.65%, respectively. All 12 patients receiving endovascular treatment survived. The factors associated with a worse outcome were younger age (52.86 ± 12.96 years, OR: 1.085, 95% CI: 1.002-1.174) and SIVR patients without DVT (OR:10.111, 95% CI: 1.637-62.443). Conclusion: This first systematic review on SIVR shows that SIVR should be highly suspected in elderly females who develop lower extremity DVT and concurrent lower abdominal pain, particularly those with a retroperitoneal mass and unstable hemodynamics. Thrombosis secondary to MTS may be the main cause of SIVR. Angiography and endovascular therapy should be prioritized for DVT patients with unexplained retroperitoneal hematoma. This study classifies SIVR into two types: iliac vein rupture alone and iliac vein rupture with DVT. These findings provide critical insights for clinicians to accurately diagnose and manage SIVR, thereby improving patient outcomes.

Antidepressive mechanisms of rhynchophylline in mice with chronic unpredictable stress-induced depression.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla ([Mi] Jack) (gouteng) exerts antidepressive effects. Rhynchophylline (RH), a major component of U. rhynchophylla, exerts similar pharmacological effects to those of gouteng. Thus, RH may have antidepressive effects. AIM OF THE STUDY: To investigate the anti-depressive effects of RH in chronic unpredictable mild stress (CUMS)-induced depressive mice. The anti-depressive mechanism of RH determined by measuring the 5-HT levels, the expressions of cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in cortex and hippocampus. MATERIALS AND METHODS: The behaviors of CUMS-induced depressive mice were measured using an open field test (OFT), forced swimming test (FST), and tail suspension test (TST). 5-HT levels were measured using an ELISA kits. The expressions of BDNF and CREB were determined using western blot test. RESULTS: RH increased the frequency of rearing and grooming in the OFT and decreased the immobility time in the FST and TST. RH effectively increased the 5-HT level and BDNF and CREB expressions in the cortex and hippocampus. CONCLUSION: Our findings indicate that the antidepressive mechanism of RH is related to increased levels of 5-HT from regulating CREB and BDNF expressions in cortex and hippocampus.

Significance of strictly defined idiopathic tricuspid regurgitation.

BACKGROUND: Moderate to severe tricuspid regurgitation (TR) is known to cause right ventricular (RV) failure and death. Although TR is traditionally classified as primary or secondary, recently, a new class of TR called idiopathic TR has been proposed, with varying definitions among different studies. METHODS: The data were retrospectively collected for the period of January to June 2018 for 8711 patients from the patient cohort of the National Cheng Kung University Hospital echocardiography laboratory. A total of 670 patients (7.7%) with moderate-to-severe TR were included. Idiopathic TR was diagnosed strictly using a new systematic approach. RESULTS: The distribution of significant TR included 74 (11.0%) primary TR cases, 48 (7.2%) with pacemaker-related TR, 267 (39.9%) with left heart disease, 24 (3.6%) with congenital heart disease, 6 (0.9%) with RV myopathy, 105 (15.7%) with pulmonary hypertension, and 146 (21.8%) with idiopathic TR. The mean age in primary and idiopathic TR groups was older ( p = 0.004), with lower estimated pulmonary pressure ( p < 0.001), higher RV fraction area change (FAC, p < 0.001), and tricuspid annulus systolic velocity (S', p = 0.004) compared with functional TR group. Multivariate analysis showed that idiopathic TR ( p = 0.002) and primary TR ( p = 0.008) had better RV FAC than functional TR. CONCLUSION: Idiopathic TR was associated with better RV function than the other secondary TRs. Thus, idiopathic TR should be strictly defined and regarded as a distinct type of TR.

Specific Expert Learning: Enriching Ensemble Diversity via Knowledge Distillation.

In recent years, ensemble methods have shown sterling performance and gained popularity in visual tasks. However, the performance of an ensemble is limited by the paucity of diversity among the models. Thus, to enrich the diversity of the ensemble, we present the distillation approach-learning from experts (LFEs). Such method involves a novel knowledge distillation (KD) method that we present, specific expert learning (SEL), which can reduce class selectivity and improve the performance on specific weaker classes and overall accuracy. Through SEL, models can acquire different knowledge from distinct networks with various areas of expertise, and a highly diverse ensemble can be obtained afterward. Our experimental results demonstrate that, on CIFAR-10, the accuracy of the ResNet-32 increases 0.91% with SEL, and that the ensemble trained by SEL increases accuracy by 1.13%. Compared to state-of-the-art approaches, for example, DML only improves accuracy by 0.3% and 1.02% on single ResNet-32 and the ensemble, respectively. Furthermore, our proposed architecture also can be applied to ensemble distillation (ED), which applies KD on the ensemble model. In conclusion, our experimental results show that our proposed SEL not only improves the accuracy of a single classifier but also boosts the diversity of the ensemble model.

The change trend analysis of incidence of intracerebral hemorrhage in Tengzhou City,Shandong Province from 2013 to 2021 / 中华神经科杂志

Objective:To analyze the changing trend of intracerebral hemorrhage (ICH) incidence among residents with different characteristics during 9 years of comprehensive hypertension prevention and control (hypertension prevention and control) in Tengzhou from 2013 to 2021.Methods:From January 1, 2013 to December 31, 2021, the new ICH cases collected by the Center for Disease Control and Prevention in Tengzhou City were analyzed to calculate the incidence of ICH, and the trend of its distribution was analyzed among residents with different ages, sexes, and between urban and rural areas. The registered population information came from Tengzhou Public Security Bureau. Age and sex standardized incidence was calculated based on the 7th National Population Census in 2020. The Cochran-Armitage test was used to analyze the time and age trends of the incidence.Results:The overall ICH crude and standardized incidence in Tengzhou City decreased from 97.30/100 000 to 52.13/100 000 ( Z=-9.93, P<0.001) and 119.30/100 000 to 50.69/100 000 ( Z=-15.40, P<0.001) from 2013 to 2021, and both elevated to form a single peak in 2020, with 22.58% ( χ 2=24.02, P<0.001) and 18.09% ( χ 2=17.08, P<0.001) higher than in 2019, respectively. The trends in male and female incidence over the same period were similar to the overall trends, and the incidence was higher in males than in females in all years. The incidence of ICH increased with age in all years. The difference of increase in male incidence rate in 2020 was statistically significant in three age groups ≥45 years compared with 2019 (36.29%, 23.57% and 16.18%, respectively, χ 2=6.73, 4.65, 4.00, P<0.001). The incidence of ICH decreased by 70.07% and 36.23% ( Z=18.44, 5.22, P<0.001) in urban and rural areas respectively from 2013 to 2021, whereas increased by 34.15% ( χ 2=10.88, P<0.01) and 22.08% ( χ 2=18.63, P<0.001) in 2020 compared with 2019 separately. Conclusions:The incidence of ICH in Tengzhou from 2013 to 2021 showed a significant downward trend, with the decrease in the incidence of ICH in women exceeding that in men. The decrease in the incidence of ICH in urban areas exceeded that in rural areas, and male morbidity seemingly had a younger trend.

Clinical application of the convertible vena cava filter / 中华普通外科杂志

Objective:To evaluate the short-term efficacy, safety and complications of convertible vena cava filter.Methods:The clinical and follow-up data of 103 patients who were placed with the convertible vena cava filter from May 2017 to May 2018 were retrospectively analyzed.Results:The convertible vena cava filters were successfully implanted in all cases. Twenty-seven cases underwent filter conversion, and 26 cases were successfully converted (5-145 days after implantation). None of them had complications such as thrombus formation, displacement, tilt, fracture or vein wall penetration. The reasons for no conversion included age (18.4%, 19/103), high-risk patients (12.6%, 13/103), limited organ function (9.7%, 10/103), etc. Ninety-four patients (91.3%) were followed up for 6 months. One developed thrombus in the filter, 3 developed lower limb venous thrombosis without inferior vena cava occlusion, and no patients were found with symptomatic pulmonary embolism.Conclusions:The convertible vena cava filter can safely and effectively reduce the incidence of perioperative pulmonary embolism.Age, limited organ function and high-risk of thrombosis are the main reasons for the low conversion rate.

Gut microbiota controls the development of chronic pancreatitis: A critical role of short-chain fatty acids-producing Gram-positive bacteria

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G+) or Gram-negative bacteria (G-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G+ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G+ bacteria. Additionally, depletion of SCFAs-producing G+ bacteria rather than G- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G+ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G+ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model / 中国中药杂志

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.

Effect and mechanism of Xihuang Pills on rats with precancerous lesions of breast / 中国中药杂志

The purpose of this study was to explore the effect and mechanism of Xihuang Pills on rats with precancerous lesions of the breast. Of 48 healthy female rats, 8 were randomly selected as blank group, and the other 40 were treated with 7,12-dimethylbenzanthracene(DMBA) combined with estrogen and progestin to establish a model of precancerous lesions of the breast. The successfully modeled rats were randomly divided into a model group, a tamoxifen group(1.8 mg·kg~(-1)·d~(-1)), a Xihuang Pills low-dose group(0.3 g·kg~(-1)·d~(-1)), a medium-dose group(0.6 g·kg~(-1)·d~(-1)) and a high-dose group(1.2 g·kg~(-1)·d~(-1)). After 30 days of admi-nistration, the histopathological changes of viscera and breast were observed by haematoxylin and eosin(HE) staining, and the visceral index was calculated. Enzyme linked immunosorbent assay(ELISA) was used to detect the contents of estradiol(E_2) and progesterone(P) in serum. The protein expressions of vascular endothelial growth factor(VEGF) and fibroblast growth factor 2(FGF2) were detected by immunohistochemistry. The protein expressions of VEGF, vascular endothelial growth factor receptor 2(VEGFR2), phosphorylated-vascular endothelial growth factor receptor 2(p-VEGFR2), B-cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) were detected by Western blot and the mRNA expressions of VEGF, FGF2, CXC-chemokine receptor 4(CXCR4), cysteine aspartic acid-specific protease(caspase-3), and stromal cell-derived factor 1(SDF-1) were detected by real-time polymerase chain reaction(RT-PCR). HE staining revealed that the model group had some liver and kidney damages and severe hyperplastic mammary tissue, while the Xihuang Pills high-dose group had mild hyperplasia. Compared with the model group, the Xihuang Pills groups had lo-wer ovarian coefficient(P<0.05 or P<0.01) and Xihuang Pills high-dose group had lower uterine coefficient(P<0.01). ELISA results showed that compared with the model group, expressions of E_2 and P in Xihuang Pills high-dose group were significantly decreased(P<0.05 or P<0.01). Immunohistochemistry, Western blot and RT-PCR indicated that compared with the conditions in the model group, the protein and mRNA expressions of VEGF and FGF2 in the Xihuang Pills groups were down-regulated(P<0.05 or P<0.01), and the protein expression of Bcl-2 was lowered(P<0.01); there was a decrease in the protein expressions of VEGFR2 and p-VEGFR2(P<0.01), a down-regulation in the mRNA expressions of CXCR4 and SDF-1(P<0.01), while an increase in the mRNA expression of caspase-3(P<0.01) in both Xihuang Pills medium-dose and high-dose groups; the protein expression of Bax in Xihuang Pills high-dose group was increased(P<0.01). The above results indicated that Xihuang Pills can effectively intervene in precance-rous lesions of the breast, and the mechanism may be related to the regulation of E_2 and P secretion as well as the inhibition of angiogenesis and chemokine receptor expression, thus controlling the occurrence of precancerous lesions of the breast in rats.