Effect of CHRDL1 on angiogenesis and metastasis of colorectal cancer cells via TGF-ß/VEGF pathway.

Colorectal cancer (CRC) is a common digestive tract tumor with the third incidence and death in the world. There is still an urgent need for effective therapeutic targets and prognostic markers for CRC. Herein, we report a novel potential target and marker, Chordin like-1 (CHRDL1). The function of CHRDL1 has been reported in gastric cancer, breast cancer, and oral squamous cell carcinoma. However, the biological effect of CHRDL1 in CRC remains unrevealed. Transwell and tube formation experiments were used to determine the biological function of CHRDL1. Western blot and rescue experiments were used to determine the specific mechanisms of CHRDL1. Results showed CHRDL1 is significantly downregulated in CRC cell lines and tissues. In vitro, experiments confirmed that CHRDL1 can inhibit cell growth, migration, invasion, angiogenesis and reverse epithelial-mesenchymal transformation. In vivo, experiments proved that it can inhibit tumor growth and metastasis. Mechanistically, we newly find that CHRDL1 exerts biological functions through the transforming growth factor-beta (TGF-ß)/vascular endothelial growth factor signaling axis in vitro and in vivo. Therefore, we concluded that CHRDL1 reduces the growth, migration, and angiogenesis of CRC cells by downregulating TGF-ß signaling. Our new findings on CHRDL1 may provide a basis for clinical antiangiogenesis therapy and the prognosis of CRC.

Tumor suppressor CLCA1 inhibits angiogenesis via TGFB1/SMAD/VEGF cascade and sensitizes hepatocellular carcinoma cells to Sorafenib.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly vascularized tumor with a poor prognosis. Novel vascular-related therapeutic targets and prognostic markers remain urgently needed. AIMS: To investigate the role and mechanism of CLCA1 in hepatocellular carcinoma. METHODS: Immunofluorescence, Co-immunoprecipitation and rescue experiment were used to determine the specific mechanisms of CLCA1. Chemosensitivity assay was used to measure the impact of CLCA1 on Sorafenib. RESULTS: CLCA1 was dramatically downregulated in hepatocellular carcinoma cell lines and tissues. Ectopic expression of CLCA1 induced cell apoptosis and G0/G1 phase arrest while suppressed cell growth, inhibited migration and invasion, reversal of epithelial mesenchymal transition in vitro and reduced xenograft tumor growth in vivo. Mechanistically, CLCA1 could co-localize and interact with TGFB1, thereby suppressing HCC angiogenesis through the TGFB1/SMAD/VEGF signaling cascade in vitro and in vivo. Moreover, CLCA1 also enhanced the sensitivity of HCC cells to the first-line targeted therapy, Sorafenib. CONCLUSION: CLCA1 sensitizes HCC cells to Sorafenib and suppresses hepatocellular carcinoma angiogenesis through downregulating TGFB1 signaling cascade. This newly identified CLCA1 signaling pathway may help guide the anti-angiogenesis therapies for hepatocellular carcinoma. We also support the possibility of CLCA1 being a prognostic biomarker for hepatocellular carcinoma.

Tumour suppressor ABCA8 inhibits malignant progression of colorectal cancer via Wnt/ß-catenin pathway.

BACKGROUND: Colorectal cancer (CRC) is one of the most commonly diagnosed malignant tumours of the digestive tract, and new therapeutic targets and prognostic markers are still urgently required. However, the role and molecular mechanisms of ATP binding cassette subfamily A member 8 (ABCA8) in CRC remain unclear. METHODS: Databases and clinical specimens were analysed to determine the expression level of ABCA8 in CRC. Colony formation, CCK-8 and Transwell assays were conducted to determine cell proliferation, viability, migration and invasion. Flow cytometry was used to detect cell cycle progression and apoptosis. Western blot and rescue experiments were performed to determine the specific mechanisms of action of ABCA8. RESULTS: ABCA8 expression is dramatically down-regulated in CRC tissues and cell lines. Ectopic expression of ABCA8 induced apoptosis and cell cycle arrest in vitro, inhibited cell growth, suppressed migration and invasion, reversed epithelial-mesenchymal transition and suppressed xenograft tumour growth and metastasis in vivo. Mechanistically, ABCA8 inhibited CRC cell proliferation and metastasis through the Wnt/ß-catenin signalling pathway, both in vitro and in vivo. CONCLUSION: We verified that ABCA8 inhibits the malignant progression of CRC through the Wnt/ß-catenin pathway. This newly discovered ABCA8-Wnt-ß-catenin signalling axis is probably helpful in guiding the clinical diagnosis and treatment of CRC.

Surface barriers to mass transfer in nanoporous materials for catalysis and separations.

Surface barriers to mass transfer in various nanoporous materials have been increasingly identified. These past few years especially, a significant impact on catalysis and separations has come to light. Broadly speaking, there are two types of barriers: internal barriers, which affect intraparticle diffusion, and external barriers, which determine the uptake and release rates of molecules into and out of the material. Here, we review the literature on surface barriers to mass transfer in nanoporous materials and describe how the existence and influence of surface barriers has been characterized, aided by molecular simulations and experimental measurements. As this is a complex, evolving research topic, without consensus from the scientific community at the time of writing, we present various current viewpoints, not always in agreement, on the origin, nature, and function of such barriers in catalysis and separation. We also emphasize the need for considering all the elementary steps of the mass transfer process in optimally designing new nanoporous and hierarchically structured adsorbents and catalysts.

Inositol Alleviates Pulmonary Fibrosis by Promoting Autophagy via Inhibiting the HIF-1α-SLUG Axis in Acute Respiratory Distress Syndrome.

The effective remission of acute respiratory distress syndrome- (ARDS-) caused pulmonary fibrosis determines the recovery of lung function. Inositol can relieve lung injuries induced by ARDS. However, the mechanism of myo-inositol in the development of ARDS is unclear, which limits its use in the clinic. We explored the role and mechanism of myo-inositol in the development of ARDS by using an in vitro lipopolysaccharide- (LPS-) established alveolar epithelial cell inflammation model and an in vivo ARDS mouse model. Our results showed that inositol can alleviate the progression of pulmonary fibrosis. More significantly, we found that inositol can induce autophagy to inhibit the progression pulmonary fibrosis caused by ARDS. In order to explore the core regulators of ARDS affected by inositol, mRNA-seq sequencing was performed. Those results showed that transcription factor HIF-1α can regulate the expression of SLUG, which in turn can regulate the key gene E-Cadherin involved in cell epithelial-mesenchymal transition (EMT) as well as N-cadherin expression, and both were regulated by inositol. Our results suggest that inositol activates autophagy to inhibit EMT progression induced by the HIF-1α/SLUG signaling pathway in ARDS, and thereby alleviates pulmonary fibrosis.

The Architecture of Inactivated SARS-CoV-2 with Postfusion Spikes Revealed by Cryo-EM and Cryo-ET.

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) resulted from the outbreak of SARS-CoV-2 in December 2019. Currently, multiple efforts are being made to rapidly develop vaccines and treatments to fight COVID-19. Current vaccine candidates use inactivated SARS-CoV-2 viruses; therefore, it is important to understand the architecture of inactivated SARS-CoV-2. We have genetically and structurally characterized ß-propiolactone-inactivated viruses from a propagated and purified clinical strain of SARS-CoV-2. We observed that the virus particles are roughly spherical or moderately pleiomorphic. Although a small fraction of prefusion spikes are found, most spikes appear nail shaped, thus resembling a postfusion state, where the S1 protein of the spike has disassociated from S2. Cryoelectron tomography and subtomogram averaging of these spikes yielded a density map that closely matches the overall structure of the SARS-CoV postfusion spike and its corresponding glycosylation site. Our findings have major implications for SARS-CoV-2 vaccine design, especially those using inactivated viruses.

A systematic study on the prevention and treatment of retinopathy of prematurity in China.

BACKGROUND: To identify the prevention situation, the main factors influencing prevention effects and to develop control measures over retinopathy of prematurity in China. METHODS: Using stratified random sampling method, we randomly selected 23 provincial and ministerial hospitals (8 in Guangdong province, 5 in Hunan province and 10 in Shaanxi province), 81 municipal hospitals (38 in Guangdong province, 19 in Hunan province and 24 in Shaanxi province), 180 district and county hospitals (76 in Guangdong province, 57 in Hunan province and 47 in Shaanxi province) in China. A total of 284 hospitals were enrolled in the study, with questionnaires distributed investigating the status and constrain factors of ROP presentation. Significant outcomes were analyzed thereafter by SPSS 19.0. RESULTS: The screening rate of ROP in medical institutions from eastern, central and western China were 84.6%, 35.0% and 56.7%, respectively. The screening rate of tertiary and secondary medical institutions were 84.6% and 25.7% in the eastern, 35.0% and 4.9% in the central, 56.7% and 5.9% in the western region. Screening was carried out better in the tertiary than that in the secondary and primary institutions. Treatment for ROP was available in 15.7% of all the tertiary hospitals surveyed. Lack of professionals, equipments and technologies were considered to be major restrain factors for screening. CONCLUSIONS: The ROP screening and treatment status have demonstrated significant regional diversity due to uneven distribution of medical resources in China. Developed areas had established intraregional cooperation models, whereas less-developed areas should consider set up a large-scale, three-level ROP prevention network. It is of paramount importance that education and training towards ophthalmologists should be vigorously strengthened. It is strongly recommended that implement ROP telemedicine and integrated ROP prevention and management platforms through the Internet should be established.

The association between obesity related adipokines and risk of breast cancer: a meta-analysis.

The risk of breast cancer is significantly increased among obese women as the deleterious adipokines can be over secreted and beneficial adipokines can be hyposecreted. We aim to evaluate the association between obesity-associated adipokines and breast cancer. We searched PubMed, EMBASE, Web of Science, and Chinese Biomedical Literature (CBM) databases for studies reporting association of obesity related adipokines with breast cancer published before Sept. 15, 2015. Initially, 26783 publications were identified, and later, 119 articles were selected for further meta-analysis. Out of these 119 studies, twenty-six studies had reported adipokine levels among obese and non-obese healthy subjects and ninety-three studies had reported adipokine levels among patients with breast cancer. The subjects with BMI >25 kg/m2 had significantly lower adiponectin levels and higher leptin and tumor necrosis factor-α (TNF-α) levels than those with BMI <25 kg/m2. Decreased concentrations of adiponectin, and increased concentrations of leptin, IL-6, IL-8, TNF-α, resistin and visfatin were significantly associated with risk of breast cancer. Adipokine levels were strongly associated with breast cancer among Asian women as compared to non-Asian women. Our results might explain the relationship of obesity, adipokine levels and risk of breast cancer, especially in Asian women.

Novel technique for laparoscopic harvesting of latissimus dorsi flap with prosthesis implantation for breast reconstruction: A preliminary study with 2 case reports.

BACKGROUD: An important drawback of the traditional technique for harvesting latissimus dorsi (LD) myocutaneous flap is a long, posterior donor-site incision. Current techniques involve endoscopic or robotic harvesting via a combined approach of open and closed surgery, which necessitates an open axillary incision and the use of special retractors. In this paper, we introduce a fully enclosed laparoscopic technique for harvesting LD flap (LDF) using only 3 small trocar ports. This technique eliminates the need for axillary and donor-site incisions and specialized retractors and considerably reduces the incision size. METHODS: We performed laparoscopic harvesting of LDF with prosthesis implantation for immediate breast reconstruction (IBR) after nipple-sparing mastectomy in 2 patients with malignant breast neoplasm who wished to avoid a long scar on the back. RESULTS: IBR using this technique was uneventful in both cases, without any donor-site complications or flap failure. Both patients were satisfied with the esthetic results of the procedure, especially the absence of a visible scar on the back. CONCLUSION: Enclosed laparoscopic harvesting of LDF is simpler and less invasive than the traditional methods. These preliminary results warrant further evaluation in a larger population to validate the benefits of this technique.

A meta-analysis of biomarkers for the prognosis of triple-negative breast cancer patients.

UNLABELLED: Identification of biomarkers that has the ability to predict triple-negative breast cancer (TNBC) prognosis especially in patients undergoing chemotherapy is very important. METHODS: The cohort studies that reported association between chemotherapy biomarker expression and survival outcome in TNBC patients were included in our analysis. RESULTS: The promising markers that emerged for the prediction of disease-free survival and overall survival included Ki67, BRCA1 methylation and LC3B. Furthermore, Ki67 appeared to be also significantly associated with worse disease-free survival in TNBC patients who received anthracycline-based chemotherapy. CONCLUSION: This meta-analysis demonstrated that in TNBC patients receiving chemotherapy, Ki67 is a predictor for poor prognosis, BRCA1 methylation and LC3B are also potential prognostic markers. In addition, the TNBC patients with high Ki67 expression seems to display resistance to anthracycline-based chemotherapy.

A Cross-sectional Study Assessing Predictors of Essential Medicines Prescribing Behavior Based on Information-motivation-behavioral Skills Model among County Hospitals in Anhui, China.

BACKGROUND: The self-consciousness and practicality of preferentially prescribed essential medicines (EMs) are not high enough in county hospitals. The purposes of this study were to use the information-motivation-behavioral skills (IMB) model to identify the predictors of essential medicines prescribing behavior (EMPB) among doctors and to examine the association between demographic variables, IMB, and EMPB. METHODS: A cross-sectional study was carried out to assess predictive relationships among demographic variables and IMB model variables using an anonymous questionnaire administered in nine county hospitals of Anhui province. A structural equation model was constructed for the IMB model to test the instruments using analysis of moment structures 17.0. RESULTS: A total of 732 participants completed the survey. The average age of the participants was 37.7 ± 8.9 years old (range: 22-67 years old). The correct rate of information was 90.64%. The average scores of the motivation and behavioral skills were 45.46 ± 7.34 (hundred mark system: 75.77) and 19.92 ± 3.44 (hundred mark system: 79.68), respectively. Approximately half (50.8%) of respondents reported that the proportion of EM prescription was below 60%. The final revised model indicated a good fit to the data (χ2 /df = 4.146, goodness of fit index = 0.948, comparative fit index = 0.938, root mean square error of approximation = 0.066). More work experience (ß = 0.153, P < 0.001) and behavioral skills (ß = 0.449, P < 0.001) predicted more EMPB. Higher income predicted less information (ß = -0.197, P < 0.001) and motivation (ß = -0.204, P < 0.001). Behavioral skills were positively predicted by information (ß = 0.135, P < 0.001) and motivation (ß = 0.742, P < 0.001). CONCLUSION: The present study predicted some factors of EMPB, and specified the relationships among the model variables. The utilization rate of EM was not high enough. Motivation and behavior skills were crucial factors affecting EMPB. The influence of demographic variables, such as income and work experience, on EMPB should be fully appreciated. Comprehensive intervention measures should be implemented from multiple perspectives.

Evaluation of the implementation outcomes of the Essential Medicines System in Anhui county-level public hospitals: a before-and-after study.

BACKGROUND: In August 2009, China formally established the National Essential Medicines System (NEMS) and implemented this system in the government-funded primary care medical and health institutions. After nearly four years of practice, the system has already been generalized to the county-level public hospitals. This study aimed to examine the impact on the operation of the hospitals through implementing the NEMS in Anhui Province and put forward some improvement measures. METHODS: For quantitative analyses, we distributed 21 questionnaires to 21 county-level public hospitals in Anhui Province, which had implemented the national public hospital reform. Twenty valid questionnaires were returned, response rate was 95.2 %. Questions covered storage, usage and supply of essential medicines, compensation mechanisms, insurance policies, hospital incomes, service amounts and fees from January to June in each of the years from 2011 to 2013. For qualitative study, we chose three from 21 hospitals based on geographical distribution and conducted focus group interviews based on a planned interview outline centered on the implementation status of the system. RESULTS: Following implementation, the types of essential medicines stocked and the proportion of total sales that were composed of essential medicines have increased but do not yet meet the required standards issued in the government document, which was not less than 95 % and 30 % of the total, respectively. The average financial subsidies had increased by 1,665,200 yuan, and significant increases appeared in provincial financial assistance. The average inpatient fees per visit decreased by 487.41 yuan. Increases in income from medicines during hospitalization led to increases in per-visit hospitalization fees. Unexpectedly, higher financial assistance revenue also led to higher average per-visit hospitalization fees. DISCUSSION: The guiding role of the National Essential Medicines List remains to be reinforced, and specific lists for county hospitals should be developed. Supervision was required to implement the process of guaranteeing the storage and usage of essential medicines. The compensation mechanism was far from sound, and the leverage of the health insurance policies was not obvious. Regarding the reductions in the proportion of income derived from medicines and per-visit inpatient fees, the policy had been partially successful. CONCLUSIONS: Our results showed that the implementation of the Essential Medicines System do have a beneficial role in the reduction of the drug fees and further alleviates the burden of the masses. Much effort should be made to the redesign of the compensation mechanism, mainly including the government and the medical insurance compensation, emphasizing on both the fairness and the rationality of the compensation in the future.

A Study on the Application of the Information-Motivation-Behavioral Skills (IMB) Model on Rational Drug Use Behavior among Second-Level Hospital Outpatients in Anhui, China.

BACKGROUND: The high prevalence of risky irrational drug use behaviors mean that outpatients face high risks of drug resistance and even death. This study represents the first application of the Information-Motivation-Behavioral Skills (IMB) model on rational drug use behavior among second-level hospital outpatients from three prefecture-level cities in Anhui, China. Using the IMB model, our study examined predictors of rational drug use behavior and determined the associations between the model constructs. METHODS: This study was conducted with a sample of 1,214 outpatients aged 18 years and older in Anhui second-level hospitals and applied the structural equation model (SEM) to test predictive relations among the IMB model variables related to rational drug use behavior. RESULTS: Age, information and motivation had significant direct effects on rational drug use behavior. Behavioral skills as an intermediate variable also significantly predicted more rational drug use behavior. Female gender, higher educational level, more information and more motivation predicted more behavioral skills. In addition, there were significant indirect impacts on rational drug use behavior mediated through behavioral skills. CONCLUSIONS: The IMB-based model explained the relationships between the constructs and rational drug use behavior of outpatients in detail, and it suggests that future interventions among second-level hospital outpatients should consider demographic characteristics and should focus on improving motivation and behavioral skills in addition to the publicity of knowledge.

Rabeprazole 10 mg versus 20 mg in preventing relapse of gastroesophageal reflux disease: a meta-analysis.

BACKGROUND: Several randomized controlled trials (RCTs) have compared endoscopic and symptomatic relapses in patients with erosive gastroesophageal reflux disease (GERD). We have summarized current evidence for rabeprazole 10 or 20 mg once daily for GERD maintenance treatment over 1 or 5 years. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched, through August 2012, for eligible RCTs of adults with erosive GERD. The efficacies of rabeprazole 10 and 20 mg/d were compared. RESULTS: The search identified 288 citations, and five RCTs containing 1480 patients were considered eligible. Heartburn relapse rates did not differ significantly between patients treated with rabeprazole 10 and 20 mg/d for 1 year (relative risk (RR) = 1.29; 95% confidence interval (CI): 0.97-1.72), but differed in patients treated for 5 years (RR = 1.274; 95% CI: 1.005-1.615). Endoscopic relapse rates differed significantly between rabeprazole 10 and 20 mg/d for 1 year (RR = 1.92; 95% CI: 1.21-3.06), for 5 years (RR = 1.667; 95% CI: 1.073-2.589), and in combined 1- and 5-year maintenance trials (RR = 1.785; 95% CI: 1.298-2.456). CONCLUSION: Rabeprazole 20 mg/d was superior to rabeprazole 10 mg/d in preventing endoscopic relapse of erosive GERD, but that the two dosages were equivalent in symptomatic relief over 1 year.

Prescription pattern and its influencing factors in Chinese county hospitals: a retrospective cross-sectional study.

OBJECTIVE: This study aimed to investigate prescription patterns and influencing factors in Chinese county hospitals. METHODS: Prescription quality was evaluated by five indicators proposed by WHO/INRUD. A questionnaire for doctors was designed by our research group. All internists, surgeons, obstetricians, gynecologists and pediatricians from 10 county hospitals in Anhui province were asked to fill the questionnaire. Their prescriptions from May 2011 to April 2012 were analyzed. RESULTS: Three-hundred and thirty-seven doctors completed valid questionnaires, and 5099 prescriptions were analyzed. The average number of drugs per prescription was 3.52±2.31; the average percentage of generic drugs, antibiotic usage, injection drug usage, and drugs prescribed from the national essential drug list were 96.12%, 29.90%, 20.02% and 48.85%, respectively. Differences in final academic degree and specialty led to differences in all of the five prescription quality indicators. The older doctors tended to use more antibiotics. Doctors with more education, more training on rational drug use, and better acquisition of medicine knowledge prescribe a lower percentage of generic drugs. Moreover, the more supportive the doctor's attitude to national essential medicine policy, the higher the percentage of generic drugs were prescribed. A higher level of medical knowledge was associated with a higher percentage of drugs prescribed from the essential drugs list. CONCLUSIONS: Promoting the education of medical knowledge on doctors, reinforcing the publicity of rational drug use to doctors, and initiating the performance evaluation for doctors are effective ways for improving prescription quality in Chinese county hospitals.