[Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase â ¢ clinical trial].

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.

[Value of dual-layer spectral detector CT in preoperative prediction of lymph node metastasis of gastric cancer].

Objective: To investigate the value of dual-layer spectral detector CT(SDCT) in preoperative prediction of lymph node (LN) metastasis of gastric cancer. Methods: From January 2019 to January 2021, the clinical and imaging data of 130 gastric cancer patients(93 males and 37 females, aged from 37 to 84 years)confirmed by pathology in the Zhongshan hospital of Xiamen University were retrospectively collected. According to the status of lymph node metastasis, those patients were divided into metastatic LNs group (n=104) and nonmetastatic LNs group (n=26). The maximum diameter of gastric cancer on spectral CT images, CT Values of lesions in 40, 50, 60, 70. KeV monoenergetic image of arterial and Venous phase (CT40 keV, CT50 keV, CT60 keV, CT70 keV), iodine concentration (IC) and effective atomic number (Zeff) were measured, then the normalized IC(NIC) and spectral curve(K(40-70)) value were calculated. The differences of each parameter derived from spectral CT between the two groups were compared, and a logistic regression model was constructed. The ROC curves and area under the curve (AUC) were conducted to evaluate the diagnostic performance of each parameter and Delong test was used to compare the difference of each AUC. Results: Compared to nonmetastatic LNs group, metastatic LNs group had higher maximum diameter of tumor, CT40 keV, CT50 keV, CT60 keV, CT70 keV, IC, NIC, Zeff, and K(40-70) values on venous phase (the representative parameter is Zeff: 8.4 (8.2, 8.5) vs 8.2 (8.1, 8.3)) (all P<0.05). The proportion of patients with lower histology differentiated degree, higher T grade and positive carcino embryonic antigen (CEA)were higher than that in nonmetastatic LNs (the representative parameter was CEA: 34.6%(36/104) vs 7.7%(2/26) (all P<0.05). The regression model constructed by CEA and Zeff had the highest predictive value in predicting metastatic LNs, with an AUC of 0.835(0.759-0.894), sensitivity and specificity of 83.65% and 73.08%, respectively. Conclusion: SDCT quantitative parameters on venous phase and CEA facilitate the accurate prediction of metastatic LNs in patients with gastric cancer, and the multi-parameter regression model has the highest diagnostic performance.

[Application of dynamic CT scan in the three-dimensional dynamic morphology changes of laryngeal soft tissue in unilateral vocal fold paralysis patients].

Objective: To explore the dynamic changes of three-dimensional morphology of laryngeal soft tissue and its clinical value in the unilateral vocal fold paralysis (UVFP) patients through dynamic CT scanning during the process from inspiration to phonation. Methods: From October 2017 to July 2019, a retrospective study was performed in 18 patients with UVFP (10 males and 8 females with the range of age from 29 to 75 years old) and 10 normal subjects (5 males and 5 females with the range of age from 25 to 58 years old) in Department of Voice-Otolaryngology Head and Neck Surgery, Section Two, Zhongshan Hospital Xiamen University. The laryngeal dynamic computed tomography (CT) of cine mode was performed. Ten dynamic sequence images of vocal folds movements were obtained during the process from inspiration to phonation. Based on the dynamic changes of glottic area and the displacement of cricoid cartilage. The above dynamic sequence images were divided into inspiratory phase and phonation phase as well as open phase and closed phase. The soft tissue parameters were measured respectively, including vocal folds length, width, thickness and subglottal convergence angle. Independent-sample t test was used to analyze between UVFP group and control group. Results: During the process from inspiration to phonation, the morphology of vocal folds in control group was relatively stable at inspiratory phase and closed phase in phonation. When open phase and closed phase of phonation were switching, the morphology of vocal folds changed obviously. The length of vocal folds became longer (1.19±0.10) mm, the width became wider (2.19±0.17) mm, the thickness became thinner (2.66±0.56) mm, and the subglottal convergence angle decreased (31.45±4.78)°. Compared with the controll group, in the open phase, the thickness and width of the vocal fold on affected side in the UVFP group were thinner (t=10.25, P<0.001) and wider (t=5.25, P<0.001).While in the closed phase, the subglottal convergence angle was larger (t=4.41, P=0.001).The width of the healthy side vocal fold in the UVFP was wider (t=2.54, P=0.026) than that in the control group. The differences in other parameters were not statistically significant. Conclusions: Dynamic laryngeal CT scanning provides a simple and non-invasive method for the objective and quantitative measurement of the dynamic changes of laryngeal morphology from inspiration to phonation. Compared with the control group, the characteristic dynamic changes among UVFP were observed during this particular process, which included changes of subglottal convergence angle and thickness of vocal muscle due to denervation. In addition, in UVFP group, the width of the vocal fold healthy side in the closed phase may be used to assess its compensatory function.

Downregulation of long non-coding RNA DBH-AS1 inhibits osteosarcoma progression by PI3K-AKT signaling pathways and indicates good prognosis.

OBJECTIVE: Long non-coding RNA DBH-AS1 (DBH-AS1) has emerged as a novel regulator in cancer initiation and progression of several tumors. However, the expression of DBH-AS1 in osteosarcoma and its effect on the tumorigenesis of osteosarcoma are unclear. The purpose of this study was to determine the role of DBH-AS1 in osteosarcoma progression. PATIENTS AND METHODS: The expression level of DBH-AS1 in 119 pairs of osteosarcoma tissues and five cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The association of DBH-AS1 expression with clinicopathological factors and prognosis was also analyzed. Cell proliferation was measured by Cell Counting Kit-8 (CCK-8), EdU and cell colony formation assays and apoptosis in MG63 and U2OS cells was examined by flow cytometry. Following that, transwell invasion and wound-healing assays were used to explore cell migration and invasion, respectively. The expression of the PI3K/Akt pathway-related proteins was examined by Western blot analysis. RESULTS: We observed that DBH-AS1 was distinctly overexpressed in osteosarcoma tissue and cells, and associated with lymph node status and metastasis status. Osteosarcoma patients with a higher DBH-AS1 expression showed significantly poorer overall survival than those with lower DBH-AS1 expression. Multivariate analysis demonstrated that high DBH-AS1 expression was an independent poor prognostic factor for osteosarcoma patients. Functional assays revealed that knockdown of DBH-AS1 inhibited cell proliferation, migration and invasion, while promoted apoptosis in osteosarcoma. Moreover, suppression of DBH-AS1 could inhibit the activation of the PI3K/Akt pathway, which was demonstrated by examining the expression levels of p-PI3K and p-Akt. CONCLUSIONS: Our data first reported that DBH-AS1 may act as an oncogenic lncRNA by modulating the PI3K/Akt pathway in osteosarcoma, which may serve as a candidate prognostic biomarker and target for new therapies in osteosarcoma.

Direct Detection of Carbapenem-Resistant Organisms from Environmental Samples Using the GeneXpert Molecular Diagnostic System.

In this pilot study, traditional culture and PCR methods were compared to the Cepheid GeneXpert IV molecular diagnostic system with the Xpert Carba-R assay (Carba-R assay) for detection of carbapenem resistance genes in primary environmental samples collected during a health care-related outbreak. Overall, traditional culture-dependent PCR and the Carba-R assay demonstrated 75% agreement. The Carba-R assay detected carbapenemase genes in five additional samples and in two samples that had additional genes when compared to culture-dependent PCR. The Carba-R assay could be useful for prioritizing further testing of environmental samples during health care-related outbreaks.IMPORTANCE Use of the Carba-R assay for detection of carbapenem-resistant Gram-negative organisms (CROs) can provide data for implementation of a rapid infection control response to minimize the spread of CROs in the health care setting.

Persistence of Influenza A (H1N1) Virus on Stainless Steel Surfaces.

UNLABELLED: As annual influenza epidemics continue to cause significant morbidity and economic burden, an understanding of viral persistence and transmission is critical for public health officials and health care workers to better protect patients and their family members from infection. The infectivity and persistence of two influenza A (H1N1) virus strains (A/New Caledonia/20/1999 and A/Brisbane/59/2007) on stainless steel (SS) surfaces were evaluated using three different surface matrices (2% fetal bovine serum, 5 mg/ml mucin, and viral medium) under various absolute humidity conditions (4.1 × 10(5) mPa, 6.5 × 10(5) mPa, 7.1 × 10(5) mPa, 11.4 × 10(5) mPa, 11.2 × 10(5) mPa, and 17.9 × 10(5) mPa) for up to 7 days. Influenza A virus was deposited onto SS coupons (7.07 cm(2)) and recovered by agitation and sonication in viral medium. Viral persistence was quantified using a tissue culture-based enzyme-linked immunosorbent assay (ELISA) to determine the median (50%) tissue culture infective dose (TCID50) of infectious virus per coupon. Overall, both strains of influenza A virus remained infectious on SS coupons, with an approximate 2 log10 loss over 7 days. Factors that influenced viral persistence included absolute humidity, strain-absolute humidity interaction, and time (P ≤ 0.01). Further studies on the transfer of influenza A virus from fomites by hand and the impact of inanimate surface contamination on transmission should be performed, as this study demonstrates prolonged persistence on nonporous surfaces. IMPORTANCE: This study tested the ability of two influenza A (H1N1) virus strains to persist and remain infectious on stainless steel surfaces under various environmental conditions. It demonstrated that influenza A (H1N1) viruses can persist and remain infectious on stainless steel surfaces for 7 days. Additional studies should be conducted to assess the role played by contaminated surfaces in the transmission of influenza A virus.

Clinical application of high-sensitivity cardiac troponin T test in acute myocardial infarction diagnosis.

The aim of this study was to investigate the clinical application of a high-sensitivity cardiac troponin T (hs-cTnT) test in the diagnosis of acute myocardial infarction (AMI). Serum levels of hs-cTnT and cardiac troponin I (cTnI) were detected in 240 AMI patients and 200 healthy donors and used to plot receiver operating characteristic (ROC) curves. A clinically applicable diagnostic cut-off value of hs-cTnT was determined from the ROC curve and the diagnostic accuracy of hs-cTnT and cTnI levels in AMI were compared.The serum hs-cTnT levels in the AMI group were higher than 0.014 ng/mL (the 99th percentile of the healthy population), among which hs-cTnT levels in patients with ST-segment elevation myocardial infarction (STEMI) were higher than in patients with non-STEMI (NSTEMI). The area under the ROC curve (AUC) for hs-cTnT was significantly higher than for cTnI, and the detection combining hs-cTnT and creatine kinase isoenzyme (CK-MB) further increased the AUC. When 0.014 ng/mL was set as the cut-off value for hs-cTnT, the diagnostic sensitivity for AMI reached 100% but the specificity was only 45.5%. The diagnostic ability of hs-cTnT for AMI peaked at a cut-off value of 0.035 ng/mL, resulting in the highest Youden index (0.654) and sensitivity and specificity values of 91.8 and 74.9%, respectively. The diagnostic utility of the hs-cTnT test for AMI is superior to the traditional cTnI method. However, since hs-cTnT levels of non-AMI patients can be over the diagnostic cut-off value, further studies are necessary to define clinically applicable cut-off values of hs-cTnT.

Persistence of the 2009 pandemic influenza A (H1N1) virus on N95 respirators.

In the United States, the 2009 pandemic influenza A (H1N1) virus (pH1N1) infected almost 20% of the population and caused >200,000 hospitalizations and >10,000 deaths from April 2009 to April 2010. On 24 April 2009, the CDC posted interim guidance on infection control measures in health care settings explicitly for pH1N1 and recommended using filtering face respirators (FFRs) when in close contact with a suspected- or confirmed-to-be-infected individual, particularly when performing aerosol-generating procedures. The persistence and infectivity of pH1N1 were evaluated on FFRs, specifically N95 respirators, under various conditions of absolute humidity (AH) (4.1 × 10(5) mPa, 6.5 × 10(5) mPa, and 14.6 × 10(5) mPa), sample matrices (2% fetal bovine serum [FBS], 5 mg/ml mucin, and viral medium), and times (4, 12, 24, 48, 72, and 144 h). pH1N1 was distributed onto N95 coupons (3.8 to 4.2 cm(2)) and extracted by a vortex-centrifugation-filtration process, and the ability of the remaining virus to replicate was quantified using an enzyme-linked immunosorbent assay (ELISA) to determine the log10 concentration of the infectious virus per coupon. Overall, pH1N1 remained infectious for 6 days, with an approximately 1-log10 loss of virus concentrations over this time period. Time and AH both affected virus survival. We found significantly higher (P ≤ 0.01) reductions in virus concentrations at time points beyond 24 to 72 h (-0.52-log10 reduction) and 144 h (-0.74) at AHs of 6.5 × 10(5) mPa (-0.53) and 14.6 × 10(5) mPa (-0.47). This research supports discarding respirators after close contact with a person with suspected or confirmed influenza infection due to the virus's demonstrated ability to persist and remain infectious.

Improved anti-apoptotic and anti-remodeling potency of bone marrow mesenchymal stem cells by anoxic pre-conditioning in diabetic cardiomyopathy.

BACKGROUND: Bone marrow mesenchymal stem cells (MSC) mediate their protection by paracrine mechanism under ischemic conditions and anoxic pre-conditioning (AP) of MSC strongly enhances their survival and regenerative capacity. However, there is no report about the therapeutic potency of MSC transplantation on diabetic cardiomyopathy (DCM), an important cause of heart failure. METHODS AND RESULTS: Four months after streptozotocin injection, diabetic rats were randomly given an intramyocardial injection of one of the following: DMEM, MSC, or AP-MSC (no.=10 for each group). Two weeks after transplantation, MSC, especially AP-MSC greatly increased the fractional shortening of diabetic heart (p<0.01, respectively). AP-MSC increased the capillary density of diabetic myocardium and attenuated myocardial fibrosis (p<0.01, respectively) by increasing the activity of matrix metalloproteinase-2 and inhibitiing transforming growth factor beta-1 (p<0.01, respectively). AP-MSC are anti-apoptotic in the rat DCM model, possibly mediated through cardiac upregulation of Bcl-2/Bax ratio (p<0.05) and inhibiting the expression and activation of caspase- 3 (p<0.01). CONCLUSION: Intramyocardial transplantation of MSC has a protective effect on diabetic myocardium and anoxic pre-conditioning can enhance this protective effect. AP-MSC transplantation improved cardiac function in the rat DCM model, possibly through an anti-apoptotic effect on diabetic myocarium and attenuation of cardiac remodeling.