Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention in acute coronary syndromes (IVUS-ACS): a two-stage, multicentre, randomised trial.

BACKGROUND: Intravascular ultrasound-guided percutaneous coronary intervention has been shown to result in superior clinical outcomes compared with angiography-guided percutaneous coronary intervention. However, insufficient data are available concerning the advantages of intravascular ultrasound guidance for patients with an acute coronary syndrome. This trial aimed to investigate whether the use of intravascular ultrasound guidance, as compared with angiography guidance, improves the outcomes of percutaneous coronary intervention with contemporary drug-eluting stents in patients presenting with an acute coronary syndrome. METHODS: In this two-stage, multicentre, randomised trial, patients aged 18 years or older and presenting with an acute coronary syndrome at 58 centres in China, Italy, Pakistan, and the UK were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention or angiography-guided percutaneous coronary intervention. Patients, follow-up health-care providers, and assessors were masked to random assignment; however, staff in the catheterisation laboratory were not. The primary endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularisation at 1 year after randomisation. This trial is registered at ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Aug 20, 2019 and Oct 27, 2022, 3505 patients with an acute coronary syndrome were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention (n=1753) or angiography-guided percutaneous coronary intervention (n=1752). 1-year follow-up was completed in 3504 (>99·9%) patients. The primary endpoint occurred in 70 patients in the intravascular ultrasound group and 128 patients in the angiography group (Kaplan-Meier rate 4·0% vs 7·3%; hazard ratio 0·55 [95% CI 0·41-0·74]; p=0·0001), driven by reductions in target vessel myocardial infarction or target vessel revascularisation. There were no significant differences in all-cause death or stent thrombosis between groups. Safety endpoints were also similar in the two groups. INTERPRETATION: In patients with an acute coronary syndrome, intravascular ultrasound-guided implantation of contemporary drug-eluting stents resulted in a lower 1-year rate of the composite outcome of cardiac death, target vessel myocardial infarction, or clinically driven revascularisation compared with angiography guidance alone. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Rare earth upconversion luminescent composite based on energy transfer for specific and sensitive detection of cysteine.

Abnormal levels of thiols in cysteine (Cys) have been shown to be associated with growth retardation, skin lesions, and neurotoxicity in humans. Herein, we designed and synthesized a rare earth upconversion luminescent (UCL) nanocomposite probe UCNP-PEG-NOF1 for the UCL detection of Cys using NOF1 developed by our group as a Cys probe. The core structure of rare earth nanoparticles can absorb light at 980 nm and convert it into visible light. The detection principle of Cys was based on the change in absorption peak before and after the reaction between NOF1 and Cys, as well as the change in UCL intensity. The rare earth nanocomposite in the probe could be excited by near-infrared light and had low background fluorescence and strong penetration ability; thus, the probe was successfully employed to specifically and sensitively detect Cys with a low background signal. Overall, the developed UCNP-PEG-NOF1 probe had good selectivity and high sensitivity for Cys; its detection limit was as low as 83 nM.

Modeling study on the roles of the deposition and transport of PM2.5 in air quality changes over central-eastern China.

The role of PM2.5 (particles with aerodynamic diameters ≤ 2.5 µm) deposition in air quality changes over China remains unclear. By using the three-year (2013, 2015, and 2017) simulation results of the WRF/CUACE v1.0 model from a previous work (Zhang et al., 2021), a non-linear relationship between the deposition of PM2.5 and anthropogenic emissions over central-eastern China in cold seasons as well as in different life stages of haze events was unraveled. PM2.5 deposition is spatially distributed differently from PM2.5 concentrations and anthropogenic emissions over China. The North China Plain (NCP) is typically characterized by higher anthropogenic emissions compared to southern China, such as the middle-low reaches of Yangtze River (MLYR), which includes parts of the Yangtze River Delta and the Midwest. However, PM2.5 deposition in the NCP is significantly lower than that in the MLYR region, suggesting that in addition to meteorology and emissions, lower deposition is another important factor in the increase in haze levels. Regional transport of pollution in central-eastern China acts as a moderator of pollution levels in different regions, for example by bringing pollution from the NCP to the MLYR region in cold seasons. It was found that in typical haze events the deposition flux of PM2.5 during the removal stages is substantially higher than that in accumulation stages, with most of the PM2.5 being transported southward and deposited to the MLYR and Sichuan Basin region, corresponding to a latitude range of about 24°N-31°N.

A new Mfn-2 related synthetic peptide promotes vascular smooth muscle cell apoptosis via regulating the mitochondrial apoptotic pathway by inhibiting Akt signaling.

BACKGROUND: Restenosis after angioplasty is a major challenge for the treatment of coronary artery diseases. Facilitation of vascular smooth muscle cell (VSMC) apoptosis may be an attractive approach to decrease the incidence of restenosis. We synthesized a 16-amino acid mitofusin-2 (Mfn-2) gene related peptide (MRSP) based on the sequence of the p21ras signature motif, the smallest functional sequence of the Mfn-2 gene with proapoptotic properties in VSMC. We investigated whether MRSP enhanced apoptotic activities to inhibit VSMC accumulation and neointimal hyperplasia in rats with carotid balloon injury. METHODS: VSMCs were treated with different concentrations of MRSP, the PI3K agonist 740 Y-P and the inhibitor LY294002. Cell apoptosis and related pathway molecules were assessed. MRSP was also given to rats with carotid artery balloon injury. Neointimal hyperplasia and cell apoptotic pathways were detected. RESULTS: In vitro experiments revealed that MRSP treatment significantly increased VSMC apoptosis and induced increases in procaspase-9 cleavage, caspase-3 activation, cytochrome c release from mitochondria to the cytoplasm and the Bax/Bcl-2 ratio but not caspase-8 expression, indicating that the mitochondrial apoptotic cascade was activated by MRSP, which might be attributed to suppression of the PI3K/Akt signaling pathway. We further found that the PI3K agonist 740 Y-P prevented and that the inhibitor LY294002 strengthened the proapoptotic effects of MRSP. MRSP strongly inhibited neointimal hyperplasia and VSMC accumulation, but increased VSMC apoptosis in the vascular wall after balloon injury. Moreover, MRSP substantially enhanced Bax and cleaved caspase-3 expression and decreased Bcl-2 levels in intima, accompanied by decreased levels of phosphorylated Akt and PI3K in vivo. CONCLUSIONS: Taken together, the present study showed that MRSP treatment results in a strong proapoptotic effect by activating the mitochondrial apoptotic cascade through suppression of the PI3K/Akt pathway.

Rosuvastatin exerts anti-atherosclerotic effects by improving macrophage-related foam cell formation and polarization conversion via mediating autophagic activities.

BACKGROUND: Atherosclerosis is a chronic vascular disease posing a great threat to public health. We investigated whether rosuvastatin (RVS) enhanced autophagic activities to inhibit lipid accumulation and polarization conversion of macrophages and then attenuate atherosclerotic lesions. METHODS: All male Apolipoprotein E-deficient (ApoE-/-) mice were fed high-fat diet supplemented with RVS (10 mg/kg/day) or the same volume of normal saline gavage for 20 weeks. The burden of plaques in mice were determined by histopathological staining. Biochemical kits were used to examine the levels of lipid profiles and inflammatory cytokines. The potential mechanisms by which RVS mediated atherosclerosis were explored by western blot, real-time PCR assay, and immunofluorescence staining in mice and RAW264.7 macrophages. RESULTS: Our data showed that RVS treatment reduced plaque areas in the aorta inner surface and the aortic sinus of ApoE-/- mice with high-fat diet. RVS markedly improved lipid profiles and reduced contents of inflammatory cytokines in the circulation. Then, results of Western blot showed that RVS increased the ratio LC3II/I and level of Beclin 1 and decreased the expression of p62 in aortic tissues, which might be attributed to suppression of PI3K/Akt/mTOR pathway, hinting that autophagy cascades were activated by RVS. Moreover, RVS raised the contents of ABCA1, ABCG1, Arg-1, CD206 and reduced iNOS expression of arterial wall, indicating that RVS promoted cholesterol efflux and M2 macrophage polarization. Similarly, we observed that RVS decreased lipids contents and inflammatory factors expressions in RAW264.7 cells stimulated by ox-LDL, accompanied by levels elevation of ABCA1, ABCG1, Arg-1, CD206 and content reduction of iNOS. These anti-atherosclerotic effects of RVS were abolished by 3-methyladenine intervention. Moreover, RVS could reverse the impaired autophagy flux in macrophages insulted by chloroquine. We further found that PI3K inhibitor LY294002 enhanced and agonist 740 Y-P weakened the autophagy-promoting roles of RVS, respectively. CONCLUSIONS: Our study indicated that RVS exhibits atheroprotective effects involving regulation lipid accumulation and polarization conversion by improving autophagy initiation and development via suppressing PI3K/Akt/mTOR axis and enhancing autophagic flux in macrophages.

Manifestation of cardiac injury in hospitalised patients with COVID-19.

BACKGROUND: COVID-19 has been sweeping the world since it emerged in late December 2019. However, little is known about cardiac injury in hospitalised COVID-19 patients. This study is to investigate the incidence and characteristics of myocardial injury in COVID-19 patients admitted in hospital. METHODS: Fifty-four COVID-19 patients were enrolled in one ward in Tongji Hospital, Wuhan, China, and 5 were excluded caused by missing cardiac troponin I levels. Forty-nine participants were included in the final analysis. The clinical manifestations of hospitalised patients were analysed. Patients were divided into two groups, cardiac injury group and non-cardiac injury group, based on whether cardiac troponin I was elevated. Epidemic characteristics and laboratory test results were analysed in these two group. RESULTS: The average age of patients in the cardiac injury group was older (68.0 years old) than that in the non-cardiac injury group (61.5 years old). The percentages of patients with diabetes and critically severe pneumonia in the cardiac injury group were 38.5% and 38.5% respectively. Lymphocytes were decreased in 53.1% of all enrolled patients, but this decrease was more prominent (76.9%) in the cardiac injury group than the non-cardiac injury group (44.4%). Patients in the cardiac injury group also had lower platelet counts. CONCLUSIONS: COVID-19 can cause cardiac injury in many patients. It is more common in older patients and patients with diabetes and is associated with a significant decrease in lymphocytes.

A Multicenter Study of the Prevalence of Dry Eye Disease in Chinese Refractive Surgery Candidates.

OBJECTIVE: The aim of this study was to determine the prevalence of preoperative dry eye disease and evaluate tear film function in refractive surgery candidates in China. METHODS: In this prospective noninterventional cross-sectional study, refractive surgical candidates from 13 preselected eye hospitals in China were recruited from July 2015 to February 2016. Patient histories, subjective symptoms, tear film breakup time (TBUT), ocular surface fluorescein staining, and Schirmer I tests (SIT), were assessed to conduct subgroup analysis. RESULTS: A total of 1,849 patients were recruited, 41.4% were diagnosed with dry eye disease (766/1,849) and 44.9% (830/1,849) of subjects had a positive history of contact lens (CL) wear. The overall mean TBUT and SIT values were 7.3 ± 3.7 s and 15.2 ± 8.8 mm, respectively. The total prevalence of ocular surface fluorescein staining was 23.46% (422/1,849); 44.62% of patients had TBUT <5 s and 23.20% of patients had SIT <5 mm. CL wearers were observed to have a higher prevalence of dry eye than non-CL wearers (54.1 vs. 35.2%, OR = 2.17, 95% CI: 1.77-2.65). CONCLUSIONS: In this study, the most common abnormal finding in dry eye disease was tear film instability. A high proportion of refractive surgery candidates have preexisting dry eye disease and a history of CL wear prior to surgery. Careful attention should be given to the evaluation of preoperative dry eye in refractive surgery candidates.

Targeting inflammation-associated AMPK//Mfn-2/MAPKs signaling pathways by baicalein exerts anti-atherosclerotic action.

Inflammatory responses in macrophages, endothelial cells, and vascular smooth muscle cells play crucial roles in the development of atherosclerosis. Baicalein, a flavonoid phytochemical, possesses anti-inflammatory properties, but the underlying mechanisms of its action are not fully understood. The aim of this study was to explore whether baicalein inhibited inflammatory activities in RAW264.7, HUVEC, and MOVAS cells and to analyze its underlying mechanisms. Our results showed that baicalein treatment effectively reduced the levels of IL-6, TNF-α, PAI-1, and MMP-9 released by these cells upon stimulation with Ang II or ox-LDL. We discovered that the molecular mechanisms underlying baicalein suppression of the generation of proinflammatory cytokines were associated with the inhibition of MAPK/NF-κB pathway activity. Moreover, Ang II and ox-LDL intervention decreased the content of Mfn-2 in the three types of cells, but incubation of baicalein alleviated the Ang II/ox-LDL-induced reduction of Mfn-2 levels. Adv-Mfn2 treatment not only increased the expression of Mfn-2 but also reduced the levels of phosphorylated ERK1/2, p38, JNK, and NF-κB, followed by a decrease in the concentrations of IL-6, TNF-α, PAI-1, and MMP-9 in the supernatant. Furthermore, our findings indicated that baicalein treatment markedly suppressed the decrease in AMPK activity induced with Ang II and ox-LDL, and incubation with Compound C reversed the effects of baicalein on AMPK activation and Mfn-2 expression. In conclusion, our data suggest that baicalein shows anti-inflammatory properties, probably by activating the AMPK/Mfn-2 axis, accompanied by inhibition of downstream MAPKs/NF-κB signaling transduction.

First Report of Postharvest Fruit Rot Disease of Hardy Kiwifruit Caused by Diaporthe eres in China.

Hardy kiwifruit (Actinidia arguta), as an economically important fruit crop growing in Northeast China with thin, hairless and smooth skin, is susceptible to postharvest decay. In September 2018, infected cultivar Kwilv fruits were obtained from a commercial farm in Liaoning province, northeastern China. The occurring incidence of the rot disease varied from 20% to 90% according to the fruit number in each box during a 7-day-long storage at room temperature, and the initial symptom included a small, soft, chlorosis to light brown lesion and later watery brown lesions. Pure cultures of the same characteristics were obtained from the isolated strains in four rotten fruits on PDA medium. The isolates grew into transparent radial mycelium on PDA in the first two days followed by abundant white, fluffy aerial mycelium. After 14 days, colonies formed white to light brown aerial mycelial mats with gray concentric rings, and they produced gray and embedded pycnidia. Alpha conidia of 4.4 to 8.8 µm × 1.4 to 3.3 µm (n = 50) were abundant in culture, hyaline, aseptate, ellipsoidal to fusiform, while Beta conidia at 20.5 to 28.6 µm × 1.0 to 1.4 µm (n = 50) were hyaline, long, slender, curved to hamate. These morphological characteristics were similar to Diaporthe species (anamorph: Phomopsis spp.) (Udayanga et al. 2014). For identification, DNA was extracted from three single isolates respectively , and the internal transcribed spacer (ITS) region, ß-tubulin (BT), and histone (HIS) H3 gene were amplified by using primers ITS1/ITS4 (White et al. 1990), T1/T22 (O'Donnell et al. 1997) and HIS1F/HISR (Gao et al. 2017), respectively. The three isolates produced identical sequences across all three gene regions, which were submitted to NCBI (Genbank accession numbers MT561361, MT561360 and MT855966). Nucleotide BLAST analysis revealed that the ITS sequence shared 99% homology with those of ex-type Diaporthe eres in NCBI GenBank (MG281047.1 and KJ210529.1), so did the BT sequence that had 98% identity to D. eres (MG281256.1 and KJ420799.1) and the HIS 99% identity to D. eres (MG28431.1 and MG281395.1) (Hosseini et al. 2020, Udayanga et al. 2014). Pathogenicity was tested by wound inoculation on the cv. Kwilv fruits. Five mature and healthy fruits were surface-sterilized with 1% NaClO solution, rinsed in sterile distilled water and dried. Every fruit was wounded by penetrate the peel 1-2 mm with a sterile needle, and inoculated with mycelium plugs (5 mm in diameter) of the isolate on PDA, with five inoculated with sterile PDA plugs as controls. Treated fruits were kept in sterilized transparent plastic cans separately under high humidity (RH 90 to 100%) at 28°C. After five days, the same rot symptoms were observed on all fruits inoculated with mycelium while the control remained symptomless. The fungi was re-isolated from the lesions of inoculated fruits and identified as D. eres by sequencing, thus fulfilling Koch's postulates. The pathogenicity experiment was re-performed using D. eres conidial suspension (107 conidia/ml) in sterile distilled water in October 2019 and the same results were obtained. D. eres was recently reported to cause European pear rot in Italy (Bertetti et al. 2018). To our knowledge, this is the first report of D. eres causing a postharvest rot in hardy kiwifruit in China, leading to severe disease and thus huge economic losses in Northeast China. Accordingly, effective measures should be taken to prevent its spreading to other production regions in China.

Novel swine model of colonic diverticulosis.

The pathophysiology of colonic diverticulosis has not been completely understood. The development of appropriate animal models is essential to study diverticular disease. To date, no large animal models are available for this disease condition. The objective of this study was to develop a swine model by damaging the colon wall, combined with or without a low-fiber diet to mimic the pathogenesis of diverticulosis. To create a weakness on the colon wall, collagenase was applied in vivo to degrade the collagen in the colon wall. Three groups of Yucatan minipigs were included. Group 1 (n = 12) underwent collagenase injection (CI) with a low-fiber diet for 6 mo, group 2 (n = 8) underwent CI alone with a standard swine diet for 6 mo, and group 3 (n = 12) received a low-fiber diet alone for 6 mo. We found that diverticulosis occurred in 91.7% (11 of 12) of pigs in the CI + diet group and 100% (8 of 8) in CI-alone group. Moreover, around 30-75% of colon CI spots for each pig developed diverticular lesions. Diet alone for 6 mo did not induce diverticulosis. The endoscopic and histological examinations revealed the formation of multiple wide-mouthed diverticular lesions along the descending colon. Our results provide convincing evidence of the high efficacy of the reduced colon wall strength caused by CI in the development of a swine model of diverticulosis. Low-fiber diet consumption for 6 mo had no influence on the generation time or incidence rate of diverticulosis. In this model, digestion of the collagen in the colonic wall is sufficient to cause diverticulosis. NEW & NOTEWORTHY Effective large animal models of diverticulosis are currently lacking for the study of diverticular disease. This study marks the first time that a swine model of diverticulosis was developed by damaging colon wall structure, combined with or without a low-fiber diet. We found that a defect of colon wall could result in colon diverticular lesions within 6 mo in swine. This animal model mimicking the pathological process of diverticulosis is of great clinical value.

Shexiang Baoxin Pill Alleviates the Atherosclerotic Lesions in Mice via Improving Inflammation Response and Inhibiting Lipid Accumulation in the Arterial Wall.

Epidemiological studies have demonstrated that cardiovascular diseases (CVDs) are the leading cause of death in the world. Atherosclerosis, a kind of chronic vascular disorder related to multiple pathogenic processes, has been reported to be an underlying cause of CVDs. Shexiang Baoxin Pill (SBP) is a traditional Chinese medicine formulation and has been broadly used for the treatment of CVDs in East Asia. However, whether SBP affects the development of atherosclerosis is poorly understood. The aim of this study was to investigate the antiatherosclerotic roles and relevant mechanisms of SBP in apolipoprotein E knockout mice. Our results showed that SBP treatment markedly decreased the size of atherosclerotic plaques of the entire aorta and the aortic sinus. Biochemical analyses indicated that SBP gavage improved oxidative stress in vivo, as seen by the level elevation of SOD, CAT, and GSH and the level reduction of MDA, H2O2, and MPO. Moreover, the concentration of MCP-1, IFN-γ, and IL-17A was reduced, and the content of IL-10 and TGF-ß1 was increased in the serum from SBP-treated mice. We discovered that the expression levels of inflammatory factors including VCAM-1, ICAM-1, IL-6, and IL-2 in the vascular wall of the SBP group were also decreased in comparison with those of the normal saline group. Moreover, we found that SBP alleviated the activation of inflammation-related pathways in the aorta tissue, as seen by the level elevation of Mfn2 and reduced phosphorylation of p38, JNK, and NF-κB. Furthermore, western blot showed that SBP administration reduced the level of SR-A and LOX-1 and elevated the content of LXRα, ABCA1, and ABCG1 in the arterial wall, indicating that SBP was capable of alleviating lipid influx and facilitating lipid efflux. In conclusion, our data suggested that SBP exerted antiatherosclerotic effects via improving inflammation response and inhibiting lipid accumulation.

Spatial Vulnerability of Network Systems under Spatially Local Hazards.

A hazard is often spatially local in a network system, but its impact can spread out through network topology and become global. To qualitatively and quantitatively assess the impact of spatially local hazards on network systems, this article develops a new spatial vulnerability model by taking into account hazard location, area covered by hazard, and impact of hazard (including direct impact and indirect impact), and proposes an absolute spatial vulnerability index (ASVI) and a relative spatial vulnerability index (RSVI). The relationship between the new model and some relevant traditional network properties is also analyzed. A case study on the spatial vulnerability of the Chinese civil aviation network system is conducted to demonstrate the effectiveness of the model, and another case study on the Beijing subway network system to verify its relationship with traditional network properties.

Mitofusin-2 Triggers Cervical Carcinoma Cell Hela Apoptosis via Mitochondrial Pathway in Mouse Model.

BACKGROUND/AIMS: Cervical carcinoma continues to be one of the most dangerous cancer types, and more effective therapies are urgently needed for cervical carcinoma treatment. Mitochondria-associated Mitofusin 2 has influence on the progression of many cancers. In the current study, we aimed to focus on the cell apoptotic effects of Mfn2 on cervical carcinoma HeLa cells in vitro and to try to explore its underlying mechanisms. Moreover, we investigated the anticancer potential of Mfn2 in a cervical carcinoma mouse model. METHODS: Adenovirus-Mfn2 (Adv-Mfn2) was used to deliver mfn2 into HeLa cells and tumour tissues in a nude mouse model. CCK-8, TUNEL assay, Western blot and immunohistochemical staining were performed to detect the effects of Mfn2. The mRNA level of Mfn2 was determined by quantitative realtime PCR (qRT-PCR) analysis. The effect of Mfn2 on cell apoptosis was investigated by flow cytometry. Flow cytometry was used to assess the change of the mitochondrial membrane potential of the cells treated with JC-1 assay. Mfn2, Bax, Bcl-2, cytochrome c, cleaved caspase-3, and cleaved caspase-9 protein levels were analysed by Western blot. RESULTS: Data from CCK-8 and flow cytometry showed that Mfn2 could inhibit proliferation and induce apoptosis in a dose- and time-dependent manner in HeLa cells. JC-1 test results revealed that the membrane potential of the mitochondrial decreased in a dose-dependent manner in HeLa cells after Adv-Mfn2 treatment. The data from Western blot confirmed that higher cytosolic amounts of cytochrome c with increasing doses of Adv-Mfn2 signified the onset of the intrinsic apoptotic pathway. Levels of cleaved caspase-3 and cleaved caspase-9 increased in HeLa cells with Adv-Mfn2 treatment. We also found significant increases in the Bax level and a decreased Bcl-2 level with Adv-Mfn2 treatment. We further confirmed that Mfn2 could significantly inhibit the growth of the cervical tumour in the xenografted cervical carcinoma mouse model. After a 9-day-treatment, the tumours of the Adv-mfn2 group were inhibited and induced into apoptosis. The results demonstrated that the overexpression of Mfn2 could not only increase the levels of Bax and Bid in cervical tumour cells but also decrease the phosphorylation of Bad and the expression of Bcl-2. CONCLUSION: These studies suggested that the overexpression of Mfn2 could trigger cervical tumour apoptosis in vitro and in vivo, which was related to the mitochondrial pathway, and may provide a new treatment target for cervical carcinoma.

Animal Models of Diverticulosis: Review and Recommendations.

Diverticulosis is a structural alteration of the colon tissue characterized by the development of pouch-like structures called diverticula. It afflicts a significant portion of the population in Western countries, with a higher prevalence among the elderly. Diverticulosis is believed to be the result of a synergetic interaction between inherent tissue weakness, diet, colonic microstructure, motility, and genetic factors. A validated etiology has, however, not yet been established. Non-surgical treatment is currently lacking due to this poor understanding, and surgical colon resection is the only long-term solution following recurrent complications. With rising prevalence, the burden of diverticulosis on patients and hospital resources has increased over the past several years. More efficient and less invasive treatment approaches are, thus, urgently needed. Animal models of diverticulosis are crucial to enable a preclinical assessment and evaluation of such novel approaches. This review discusses the animal models of diverticulosis that have been proposed to date. The current models require either a significant amount of time to develop diverticulosis, present a relatively low success rate, or seriously deteriorate the animals' systemic health. Recommendations are thus provided to address these pitfalls through the selection of a suitable animal and the combination of multiple risk factors for diverticulosis.

Expression levels of atherosclerosis-associated miR-143 and miR-145 in the plasma of patients with hyperhomocysteinaemia.

BACKGROUND: An elevated level of homocysteine (Hcy) in the blood is designated hyperhomocysteinaemia (Hhcy) and is regarded as a strong risk factor for the development of atherosclerosis (ATH), although the association remains controversial. Considered to be essential gene expression regulators, micro-RNAs (miRNAs) modulate cardiovascular disease development and thus can be regarded as potential biomarkers and therapeutic targets in atherosclerosis. The aim of the current study is to investigate the expression levels of atherosclerosis-associated miR-143 and miR-145 in Hhcy patients and predict the progress of atherosclerosis in Hhcy patients. METHODS: A total of 100 participants were enrolled and included normal control subjects (NC = 20), hyperhomocysteinaemia alone subjects (Hhcy = 25), hyperhomocysteinaemia and carotid artery atherosclerosis combined subjects (Hhcy + ATH = 30) and patients with standalone carotid artery atherosclerosis (ATH = 25). Plasma Hcy, supplementary biochemical parameters and carotid artery ultrasonography (USG) were measured in all participants. MicroRNA expression levels in the peripheral blood were calculated by real-time reverse transcription-polymerase chain reaction (qRT-PCR). The correlations of miR-143 and miR-145 with Hcy, blood lipid parameters and carotid artery atherosclerotic plaques were evaluated using Pearson's correlation coefficients. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the capacities of miR-143 and miR-145 for the detection of Hhcy and atherosclerosis patients. RESULTS: MiR-143 and miR-145 exhibited trends towards significance with stepwise decreases from the NC to Hhcy groups and then to the Hhcy + ATH and ATH groups. Similar results were observed in the carotid artery plaque group (Hhcy + ATH and ATH grups) compared with the no-plaque group (NC and Hhcy groups). The miR-143 expression level exhibited significant negative correlations with Hcy, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c). The miR-145 expression level exhibited significant negative correlations with Hcy, TC, triglyceride (TG) and LDL-c. MiR-143 and miR-145 exhibited the greatest area under the curves (AUCs) (0.775 and 0.681, respectively) for the detection of every Hhcy patient, including those in the Hhcy and Hhcy + ATH groups, from among all subjects. CONCLUSION: The results indicated that the levels of atherosclerosis-associated circulating miR-143 and miR-145 are linked to Hhcy. MiR-143 may be used as a potential non-invasive biomarkers of Hhcy and thus may be helpful in predicting the progress of atherosclerosis in Hhcy patients.

[Adjuvant effects of Zhenyuan capsule on chronic heart failure: Meta-analysis].

To systematically review the adjuvant effects of Zhenyuan capsule on improving the cardiac function of patients with chronic heart failure. Databases including PubMed, EMbase, the Cochrane Library, CBM, CNKI, VIP and Wanfang Data were searched electronically from inception to October 2016 to collect randomized controlled trials (RCTs) about Zhenyuan capsule for adjuvant treatment of chronic heart failure. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, Meta-analysis was performed by using RevMan 5.3 software. A total of 14 RCTs involving 1 204 patients were included. The results of Meta-analysis showed that the Zhenyuan capsule group had significantly better effectiveness in cardiac function (RR=1.27, 95%CI 1.20 to 1.35, P < 0.000 01), stroke volume (WMD=7.62, 95%CI 6.39 to 8.84,P < 0.000 01), scores of HAMA (WMD=-4.16, 95%CI -5.59 to -2.72, P < 0.000 01), psychological effect of HAMA (RR=1.47, 95%CI 1.15 to 1.89, P=0.002), and traditional Chinese medical syndrome (RR=1.46, 95%CI 1.25 to 1.72, P < 0.000 01) than those of the control group, with statistically significant differences. Current evidence showed that Zhenyuan capsule combined with routine treatment could improve the cardiac function and quality of life of patients with chronic heart failure, and with high safety. Due to the limited quantity and quality of the included studies, the above conclusion still needs to be verified by carrying out more high-quality RCTs.

Effectiveness of Valsartan/Amlodipine Single-pill Combination in Hypertensive Patients With Excess Body Weight: Subanalysis of China Status II.

Obesity is a major global health concern and is associated with hypertension. However, there is a lack of studies evaluating the effectiveness of valsartan/amlodipine single-pill combination in Chinese hypertensive patients with excess body weight uncontrolled by monotherapy. To evaluate this effectiveness and its association with obese categories, we performed a prespecified subanalysis and a post hoc analysis of patients from China status II study. In this subanalysis, 11,289 and 11,182 patients stratified by body mass index (BMI) and waist circumference (WC), respectively, were included. Significant mean sitting systolic and diastolic blood pressure (BP) reductions from baseline were observed at week 8 across all BMI and WC subgroups (P < 0.001). The percentages of patients achieving BP control were 65.2%, 62.8%, and 64.5% (men 64.5% and women 64.4%) in the overweight, obesity, and abdominal obesity subgroups, respectively. The positive association between BP control and obese categories could only be found in subgroups stratified by BMI other than WC. Our study demonstrated the effectiveness of valsartan/amlodipine single-pill combination in Chinese hypertensive patients with excess body weight uncontrolled by monotherapy, and its effectiveness was better associated with BMI than WC.

Mitofusin-2-mediated tethering of mitochondria and endoplasmic reticulum promotes cell cycle arrest of vascular smooth muscle cells in G0/G1 phase.

Mitofusin-2 (Mfn-2) is a hyperplasia suppressor. Changes in Mfn-2 expression are thought to reflect mitochondrial remodeling during cell proliferation. However, it is unclear how the participation of Mfn-2 in mitochondrial remodeling prevents cellular proliferation. Here we show that arresting vascular smooth muscle cells (VSMCs) in the G0/G1 phase by serum starvation up-regulates Mfn-2 expression and causes mitochondria to assemble into a tubular network and to attach to the endoplasmic reticulum (ER). In the S phase, short rod-shaped mitochondrial structures that were dissociated from the ER were observed. Levels of glucose, ATP, l-amino acid, and NADP(+) did not vary throughout the cell cycle. However, NAD(+) level was lower and NADH level was higher in the G0/G1 phase than in the S phase. Mitochondrial membrane potential was lower in the S phase than in the G0/G1 phase. Infecting VSMCs with an adenovirus encoding full-length Mfn-2 increased NADH level and reduced NAD(+) level, while infecting the cells with an adenovirus that silences the p21(ras) signature motif produced opposite effects. These results suggest that Mfn-2 up-regulation causes mitochondrial fusion into tubular networks and attachment to the ER, which in turn halts proliferation of VSMCs.

Increased aortic stiffness elevates pulse and mean pressure and compromises endothelial function in Wistar rats.

An increase in pulse pressure (PP) is highly associated with hypertension. The goal of this study was to determine the effect of increased aortic stiffness on PP and endothelial dysfunction as precursors to hypertension. A rat model of suddenly increased aortic stiffness by use of a nonconstrictive restraint (glue coating) on aortic surface was created to investigate the change of PP and mean arterial pressure (MAP). Group I (n = 16) underwent aorta restraint for 4 wk. Group II (n = 12) underwent aortic restraint for 4 wk, followed by restraint removal to evaluate extent of reversibility for additional 4 wk. The aortic and peripheral endothelial function was assessed by ACh-stimulated endothelium-dependent vasodilation. The level of nitrate/nitrite (NOx), endothelin-1 (ET-1), and prostacyclin (PGI2) were measured in the serum and artery tissue. We found that aortic stiffening causes a significant increase in PP and MAP (P < 0.05). The endothelial function was markedly blunted (P < 0.05) in both aorta and small peripheral artery. After removal of the restraint, the impaired endothelium function persisted in the aorta likely due to sustained deterioration of aortic wall, but was partially restored in peripheral artery. The endothelial dysfunction was correlated with a decrease in NOx and PGI2 (P < 0.05) and an increase in ET-1 (P < 0.05). Our results show that aortic stiffening results in widening of PP, which affected endothelium function through changes in synthesis of NOx, ET-1, and PGI2. These findings suggest that increased aortic stiffness may be a cause of increased PP and a precursor to hypertension.