A novel subgenotype I3 of hepatitis B virus in Guangxi, China: a 15-year follow-up study.

Genotype I of hepatitis B virus (HBV) was proposed recently following sequencing of complete HBV genomes from Vietnam and Laos. However, its long-term molecular evolution is unknown. The objectives of this study were to study the molecular evolution of this genotype from an asymptomatic HBsAg carrier from the Long An cohort over a 15-year period was studied using both NGS and clone-based sequencing. The number of complete genome sequences obtained in 2004, 2007, 2013, and 2019 are 17, 20, 19, and 10, respectively. All strains belong to subgenotype I1, except for six (five from 2007 and one from 2019) and 8 further strains from 2007 which form a cluster branching out from other subgenotype I sequences, supported by a 100% bootstrap value. Based on complete genome sequences, all of the estimated intragroup nucleotide divergence values between these strains and HBV subgenotypes I1-I2 exceed 4%. These strains are recombinants between genotype I1 and subgenotype C but the breakpoints vary. The median intrahost viral evolutionary rate in this carrier was 3.88E-4 substitutions per site per year. The Shannon entropy (Sn) ranged from 0.55 to 0.88 and the genetic diversity, D, ranged from 0.0022 to 0.0041. In conclusion, our data provide evidence of novel subgenotypes. Considering that the 8 strains disappeared after 2007, while one of the 6 strains appears again in 2019, we propose these 6 strains as a new subgenotype, provisionally designated HBV subgenotype I3 and the 8 strains as aberrant genotype.

The Effects of Sacubitril/Valsartan Compared to Olmesartan on the Blood Pressure and Glucolipid Metabolism in DM Patients with Primary Hypertension.

PURPOSE: Given the beneficial effects of sacubitril/valsartan on blood pressure generally, this study investigates its antihypertension effects in diabetes mellitus (DM) patients with primary hypertension specifically, and the effect of sacubitril/valsartan on glycolipid metabolism. METHODS: We conducted a randomized, open-label, active-controlled study to compare the antihypertension effects of sacubitril/valsartan in DM individuals with primary hypertension. The primary end point was reduction in mean systolic blood pressure (SBP) from baseline with sacubitril/valsartan vs. olmesartan at week 8. The secondary endpoints included the changes in diastolic blood pressure (DBP), daytime SBP/DBP, nighttime SBP/DBP, BP achievement (office sitting BP < 130/80 mmHg), and lipid profile. The trial was registered with chictr.org.cn (ChiCTR2200066428) on Dec 22, 2022. RESULTS: A total of 124 patients were included in the final analysis. SBP decreased to a greater extent in the sacubitril/valsartan group from baseline to 8 weeks [between-treatment difference: 3.51 mm Hg, 95% confidence interval (95% CI) 0.41 to 6.62 mm Hg, P = 0.03]. Furthermore, more patients achieved the blood pressure goal with sacubitril/valasartan (74.60% vs. 54.70%, P = 0.03). Multiple logistical regression analysis showed that sacubitril/valsartan was associated with BP achievement [odds ratio (OR) 0.33, 95% CI 0.14-0.73, P = 0.007], but the difference in SBP, DBP, day time SBP/DBP, and night time SBP/DBP reduction did not approach statistical significance. HbA1C1, total cholesterol, and low-density lipoprotein-cholesterol were lower than baseline in both groups (P < 0.05); however, there was no difference in the effects on glucose and lipid metabolism from sacubitril/valsartan compared to olmesartan. CONCLUSIONS: Sacubitril/valsartan not only provided superior BP reduction compared to olmesartan, it did so without adverse effects on glycemic control and lipid parameters in DM patients with primary hypertension.

A novel presentation of idiopathic adulthood ductopenia (IAD) in a young man.

A 24-years-old male patient was admitted to our institution for intermittent jaundice, fatigue, anorexia and dark urine which occurred six times in the past 8 years (twice in 2019). Liver function test showed elevated levels of bilirubin and liver enzymes. He had no fever, vomiting, abdominal pain or diarrhea, and denied special medication, heredity or family history. He drank alcohol occasionally.

A microfluidic generator of dynamic shear stress and biochemical signals based on autonomously oscillatory flow.

Biological cells in vivo typically reside in a dynamic flowing microenvironment with extensive biomechanical and biochemical cues varying in time and space. These dynamic biomechanical and biochemical signals together act to regulate cellular behaviors and functions. Microfluidic technology is an important experimental platform for mimicking extracellular flowing microenvironment in vitro. However, most existing microfluidic chips for generating dynamic shear stress and biochemical signals require expensive, large peripheral pumps and external control systems, unsuitable for being placed inside cell incubators to conduct cell biology experiments. This study has developed a microfluidic generator of dynamic shear stress and biochemical signals based on autonomously oscillatory flow. Further, based on the lumped-parameter and distributed-parameter models of multiscale fluid dynamics, the oscillatory flow field and the concentration field of biochemical factors has been simulated at the cell culture region within the designed microfluidic chip. Using the constructed experimental system, the feasibility of the designed microfluidic chip has been validated by simulating biochemical factors with red dye. The simulation results demonstrate that dynamic shear stress and biochemical signals with adjustable period and amplitude can be generated at the cell culture chamber within the microfluidic chip. The amplitudes of dynamic shear stress and biochemical signals is proportional to the pressure difference and inversely proportional to the flow resistance, while their periods are correlated positively with the flow capacity and the flow resistance. The experimental results reveal the feasibility of the designed microfluidic chip. Conclusively, the proposed microfluidic generator based on autonomously oscillatory flow can generate dynamic shear stress and biochemical signals without peripheral pumps and external control systems. In addition to reducing the experimental cost, due to the tiny volume, it is beneficial to be integrated into cell incubators for cell biology experiments. Thus, the proposed microfluidic chip provides a novel experimental platform for cell biology investigations.

The association of procedural variables and lipid parameters with coronary rotational atherectomy outcomes.

The aim of our study is to evaluate the association of rotational atherectomy (RA) operation procedural indices and baseline lipid parameters with the prognosis of the patients with severe coronary calcification who underwent RA. Our study population consists of 287 patients treated with RA in Fuwai Hospital from January 2013 to December 2019. We analyzed the patients' rotation procedural indices including the number of burrs, the size of burrs, approach site, the size of guiding catheter, along with the baseline level of lipoprotein(a) (Lp(a)), low-density lipoprotein-cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP) to examine the association of these measurements with the prognosis of these patients using Cox regression analysis and Kaplan-Meier survival analysis. We find that during the follow-up period of 56.7 months with the median, the use of single burr in the patients who underwent RA was significantly associated with the occurrence of cumulative major adverse cardiac events (MACE) when compared with using non-single burrs [Hazard Ratio (HR) 0.43, 95% confidence interval (95% CI) 0.24-0.77, p = 0.004] from univariate Cox regression analysis; (HR 0.36, 95% CI 0.20-0.66, p = 0.001) from multivariate Cox regression analysis In addition, we find a higher event-free survival rate in the single-burr group after Kaplan-Meier survival analysis (Log rank p = 0.0033). However, there was no significant association of the size of burrs with the occurrence of MACE (HR 0.90, 95% CI 0.47-1.73, p = 0.76). Similarly, we find no significant associations between the approach site and the occurrence of MACE (HR 0.79, 95% CI 0.24-2.53, p = 0.69), the baseline Lp(a) (HR 1.07, 95% CI 0.76-1.49, p = 0.71), the level of LDL-C (HR 0.83, 95% CI 0.55-1.26, p = 0.38) or hs-CRP (HR 0.85, 95% CI 0.45-1.58, p = 0.60). We find that the patients who receive RA with a single burr have better outcomes than those who receive RA with non-single burrs. Moreover,we find that the number of burrs used in RA instead of the size of burrs, approach site, the size of guiding catheter, or baseline levels of Lp(a), LDL-C or hs-CRP had significant association with the prognosis of RA patients.

Detection of insulinoma: one-stop pancreatic perfusion CT with calculated mean temporal images can replace the combination of bi-phasic plus perfusion scan.

OBJECTIVE: To evaluate the feasibility of one-stop pancreatic perfusion CT with mean temporal (MT) imaging replacing the combination of a bi-phasic scan plus a perfusion scan to detect insulinoma. MATERIAL AND METHODS: Forty-five patients with suspected insulinoma, who underwent both biphasic and perfusion CT, were enrolled in this retrospective study. MT datasets including images for different delineation purposes were generated by averaging 3 dynamic datasets from perfusion CT, which are MTA for arterial, MTPV for portal vein and MTO for lesions. Two readers assessed the image quality and diagnostic performance separately for biphasic and MT datasets. Radiation doses were also assessed. Paired t tests, Wilcoxon signed-rank tests and McNemar's tests were applied for comparison. RESULTS: Compared with bi-phasic CT images, image noise, SNR and CNR of the MTA and MTPV datasets were all non-inferior (noise and CNR of the portal vein, p = 0.565 and p = 0.227, respectively) or superior (p ≤ 0.001). The subjective image quality was better in the MTA and MTPV images (p < 0.001 to p = 0.004). The sensitivity and NPV of MT images were also better (95% vs 75% and 75% vs 37.5% for reader 1; 97.5% vs 72.5% and 85.7% vs 35.3% for reader 2). Omitting the bi-phasic scan resulted in a dose reduction of 25% ± 4%. CONCLUSION: MT imaging can allow pancreatic perfusion CT to be used alone without the need for an additional bi-phasic CT in the detection of insulinoma. KEY POINTS: • Mean temporal images reconstructed from perfusion CT with an averaging technique reproduce usual bi-phasic images (arterial and portal phases). • The image quality of mean temporal images is non-inferior or superior to native bi-phasic CT. The sensitivity and NPV for the diagnosis of insulinoma are better for mean temporal images than for traditional bi-phasic CT. • Mean temporal imaging can allow pancreatic perfusion CT to be used alone without the need for an additional bi-phasic CT in the detection of insulinoma. Radiation dose saving is important.

Continuous Blood Purification Ameliorates Multiple Organ Failure Through Inhibiting the Activation of the P38 MAPK Signaling Pathway in a Rat Model.

BACKGROUND/AIMS: Multiple organ failure (MOF) is a primary threat to the survival of patients with systemic inflammation. Blood purification is employed in the treatment of MOF, as an artificial kidney or artificial liver. This study focuses on the effects of continuous blood purification (CBP) on ameliorating MOF through regulating the p38 mitogen-activated protein kinase (MAPK) signaling pathway in a rat model. METHODS: A rat model of MOF was successfully established by endotoxin injection after hemorrhagic shock resuscitation. The mRNA expressions of inducible nitric oxide synthase (iNOS) and p38 MAPK of liver, kidney, and lung tissues in each group were measured by RT-qPCR at each measuring time point. To evaluate the activation of p38 MAPK signaling pathway, protein levels of phosphorylated p38 (p-p38) MAPK and p38 MAPK was measured by western blot analysis. The serum levels of nitric oxide and TNF-α were determined. RESULTS: After CBP treatment, the levels of SGPT, SGOT, Cr, and BUN were significantly declined, while the PaO2 value was increased. Expressions of p38 MAPK mRNA, iNOS mRNA, p-p38 MAPK protein and p38 MAPK protein, and nitric oxide and TNF-α levels were markedly elevated in MOF, an effect blunted by CPB. Meanwhile, pathological sections of liver, kidney, and lung tissues after CPB treatment ameliorated swelling and inflammation. CONCLUSION: Our study proved that CBP could downregulate the p38 MAPK signaling pathway, suppress iNOS expression, reduced the serum levels of nitric oxide and TNF-α, thus ameliorate symptom of MOF.

PARK7 protein translocating into spermatozoa mitochondria in Chinese asthenozoospermia.

PARK7 (DJ1) is a multifunctional oxidative stress response protein that protects cells against reactive oxygen species (ROS) and mitochondrial damage. PARK7 defects are known to cause various physiological dysfunctions, including infertility. Asthenozoospermia (AS), i.e. low-motile spermatozoa in the ejaculate, is a common cause of human male infertility. In this study, we found that downregulation of PARK7 resulted in increased levels of lipid peroxide and ROS, decreased mitochondrial membrane potential, and reduced mitochondrial complex I enzyme activity in the spermatozoa from AS patients. Furthermore, it was observed that PARK7 was translocated into the mitochondria of damaged spermatozoa in AS. Finally, we examined the oxidative state of PARK7 and the results demonstrated the enhancement of oxidation, expressed by increased sulfonic acid residues, the highest form of oxidation, as the sperm motility decreased. Taken together, these results revealed that PARK7 deficiency may increase the oxidative stress damage to spermatozoa. Our present findings open new avenues of therapeutic intervention targeting PARK7 for the treatment of AS.

DHEA down-regulates mitochondrial dynamics and promotes apoptosis of lung adenocarcinoma cells through FASTKD2.

Background: DHEA is a steroid hormone produced by the gonads, adrenal cortex, brain, and gastrointestinal tract. While the anti-obesity, anti-atherosclerosis, anti-cancer, and memory-enhancing effects of DHEA have been substantiated through cell experiments, animal studies, and human trials, the precise mechanisms underlying these effects remain unclear. Altered mitochondrial dynamics can lead to mitochondrial dysfunction, which is closely related to many human diseases, especially cancer and aging. This study was to investigate whether DHEA inhibits lung adenocarcinoma through the mitochondrial pathway and its molecular mechanism. Methods: Through animal experiments and cell experiments, the effect of DHEA on tumor inhibition was determined. The correlation between FASTKD2 expression and DHEA was analyzed by Western blot, Reverse transcription-quantitative PCR, Immunohistochemistry, and TCGA database. Results: In this study, DHEA supplementation in the diet can inhibit the tumor size of mice, and the effect of adding DHEA one week before the experiment is the best. DHEA limits the glycolysis process by inhibiting G6PDH activity, increases the accumulation of reactive oxygen species, and initiates apoptosis in the mitochondrial pathway of cancer cells. Conclusion: DHEA suppresses mitochondrial fission and promotes mitochondrial fusion by downregulating the expression of FASTKD2, thereby inhibiting tumor growth and prolonging the overall survival of lung adenocarcinoma patients, which also provides a new target for the prevention and treatment of lung adenocarcinoma.

Rationale and design of a randomized controlled trial: The effect of intensive lipid-lowering therapy with PCSK9 inhibitor on endothelial-coverage of stent strut after percutaneous coronary intervention (PCI) for patients with acute coronary syndrome (ACS): Optical coherence tomography (OCT) study (PIECES-OCT study).

Background: For the patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) for at least 1 year is recommended in the guidelines to minimize the risk of stent thrombosis. Persistently uncovered stent strut means delayed neointima formation and extend the window of time in which the stent is prone to thrombosis. Previous studies showed that statins could improve post-stenting strut endothelial coverage for patients undergoing PCI. However, there are lack of evidences on whether early initiation of proprotein convertase subtilisin/Kexin type 9 monoclonal antibody (PCSK9mAb) after PCI in ACS patients can further improve the rate of stent strut coverage on the background of oral lipid-lowering therapy (LLT). Methods: This is a single-center, randomized trial to enroll 36 patients undergoing PCI with a clinical diagnosis of non-ST-segment elevation ACS. The baseline level of low-density lipoprotein cholesterol (LDL-C) of these patients are between 1.4 mmol/L and 3.4 mmol/L. Patients will be assigned to intensive lipid-lowering therapy (LLT) with PCSK9mAb group and conventional LLT without PCSK9mAb group for 12 weeks in a clinical follow-up setting according to 1: 1 randomization. the rate of stent strut endothelial coverage by optical coherence tomography (OCT) examination at 12 weeks after enrollment between the groups will be compared. Conclusion: This will be the first study to investigate changes in the rate of stent strut endothelial coverage under intensive LLT with PCSK9mAb by OCT examination in ACS patients undergoing PCI. The finding of this study will provide clinical evidence for future research about the hypothesis of a novel strategy of "intensive LLT (PCSK9mAb + statin ± ezetimibe) combined with shortened DAPT duration" for ACS patients undergoing PCI.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: ChiCTR2200063395.

The Prognostic Value of Cardiac Troponin I in Patients with or without Three-Vessel Disease Undergoing Complete Percutaneous Coronary Intervention.

Postprocedural cardiac troponin I (cTnI) elevation commonly occurs in patients undergoing percutaneous coronary intervention (PCI); however, its prognostic value remains controversial. This study aimed to investigate the prognostic value of peak postprocedural cTnI in cardiac patients with or without three-vessel disease (TVD) undergoing complete PCI. A total of 1237 consecutive patients (77% males, mean age 58 ± 10 years) with normal baseline cTnI levels were enrolled, 439 patients (77% males, 59 ± 10 years) with TVD, and 798 patients (77% males, 57 ± 10 years) with single- or double-vessel disease (non-TVD). The primary outcome was the occurrence of major adverse cardiovascular events (MACE), defined as a composite of non-fatal MI, non-fatal stroke, unplanned revascularization, re-hospitalization due to heart failure or severe arrhythmias, and all-cause death. During the median follow-up of 5.3 years, a total of 169 patients (13.7%) developed MACE, including 73 (16.6%) in the TVD group and 96 (12.0%) in the non-TVD group (p = 0.024). After adjustment, the multivariate Cox analysis showed that hypertension (HR 1.50; 95% CI: 1.01-2.20; p = 0.042), TVD (HR 1.44; 95% CI: 1.03-2.02; p = 0.033), and cTnI ≥ 70× URL (HR 2.47; 95% CI: 1.28-4.78, p = 0.007) were independently associated with increased MACE during long-term follow-up. Further subgroup analyses showed that cTnI ≥ 70× URL was an independent predictor of MACE in TVD patients (HR 3.32, 95% CI: 1.51-7.34, p = 0.003), but not in non-TVD patients (HR 1.01, 95%CI: 0.24-4.32, p = 0.991). In conclusion, elevation of post-PCI cTnI ≥ 70× URL is independently associated with a high risk of MACE during long-term follow-up in patients with TVD, but not in those with non-TVD.

Comparison of Low-Density Lipoprotein Cholesterol (LDL-C) Goal Achievement and Lipid-Lowering Therapy in the Patients With Coronary Artery Disease With Different Renal Functions.

Aim: The aim of this study was to evaluate the relationship between renal function and low-density lipoprotein cholesterol (LDL-C) goal achievement and compare the strategy of lipid-lowering therapy (LLT) among the patients with coronary artery disease (CAD) with different renal functions. Methods: In this study, we enrolled 933 Chinese patients with CAD from September 2020 to June 2021 admitted to the Cardiometabolic Center of Fuwai Hospital in Beijing consecutively. All individuals were divided into two groups based on their estimated glomerular filtration rate (eGFR). The multiple logistical regression analysis was performed to identify and compare the independent factors which impacted LDL-C goal achievement in the two groups after at least 3 months of treatment. Results: There were 808 subjects with eGFR ≥ 60 ml/min/1.73 m2 who were divided into Group 1 (G1). A total of 125 patients with eGFR <60 ml/min/1.73 m2 were divided into Group 2 (G2). The rate of LDL-C goal attainment (LDL-C <1.4 mmol/L) was significantly lower in G2 when compared with that in G1 (24.00% vs. 35.52%, P = 0.02), even though there was no significant difference in the aspect of LLT between the two groups (high-intensity LLT: 82.50% vs. 85.60% P = 0.40). Notably, in G1, the proportion of LDL-C goal achievement increased with the intensity of LLT (23.36% vs. 39.60% vs. 64.52% in the subgroup under low-/moderate-intensity LLT, or high-intensity LLT without proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (PCSK9i), or high-intensity LLT with PCSK9i, respectively, P < 0.005). In addition, in G2, there was a trend that the rate of LDL-C goal achievement was higher in the subgroup under high-intensity LLT (26.60% in the subgroup under high-intensity LLT without PCSK9i and 25.00% in the subgroup under high-intensity LLT with PCSK9i) than that under low-/moderate-intensity LLT (15.38%, P = 0.49). Importantly, after multiple regression analysis, we found that eGFR <60 ml/min/1.73 m2 [odds ratio (OR) 1.81; 95%CI, 1.15-2.87; P = 0.01] was an independent risk factor to impact LDL-C goal achievement. However, the combination strategy of LLT was a protective factor for LDL-C goal achievement independently (statin combined with ezetimibe: OR 0.42; 95%CI 0.30-0.60; P < 0.001; statin combined with PCSK9i: OR 0.15; 95%CI 0.07-0.32; P < 0.001, respectively). Conclusion: Impaired renal function (eGFR <60 ml/min/1.73 m2) was an independent risk factor for LDL-C goal achievement in the patients with CAD. High-intensity LLT with PCSK9i could improve the rate of LDL-C goal achievement significantly. It should be suggested to increase the proportion of high-intensity LLT with PCSK9i for patients with CAD, especially those with impaired renal function.

[The clinical characteristics and prognosis of non ST segment elevation acute coronary syndrome in different genders].

OBJECTIVE: To determine gender differences in baseline characteristics and intervention treatment in relation to prognosis in patients with non-ST segment elevation acute coronary syndrome (NSTEACS). METHODS: A total of 814 patients (545 men and 269 women) with NSTEACS were randomized to early intervention (coronary angiography < 24 hours after randomization) or delayed intervention (coronary angiography > 36 hours after randomization). The primary outcome was a composite of death, myocardial infarction, or stroke at 6 months. RESULTS: Women were older and more frequently had hypertension, diabetes, and history of coronary artery disease (CAD) or chronic angina (P < 0.05 for all). Women less were smokers and had elevations in cardiac marker (P < 0.05 for both). Women who underwent angiography had no significant lesions more often, but the left main stem and/or three-vessel diseases were similar with men. In adjusted multiple logistic regression analysis, the previous myocardial infarction and severe coronary artery disease were independently associated with the risk of primary endpoint in women. On multivariate analysis for men, severe coronary artery disease delayed intervention strategy and at least 3 risk factors for CAD were independently associated with the risk of primary endpoint. CONCLUSIONS: In NSTEACS patients, different gender had the different prognostic predictor. Severe coronary diseases were as an independent predictor for both male and female patients. An early intervention strategy resulted in a beneficial effect in men which was not seen in women.

[Impact of timing of intervention on prognosis of non-ST segment elevation acute coronary syndrome patients with renal dysfunction].

OBJECTIVE: To investigate the effects of intervention treatment in relation to renal function in patients with non-ST segment elevation acute coronary syndrome (NSTEACS). METHODS: A total of 815 NSTEACS patients were randomized to receive either early intervention (coronary angiography within 24 h of randomization) or delayed intervention (coronary angiography over 36 h after randomization). Serum creatinine was determined in 781 patients at admission and glomerular filtration rate (eGFR) calculated by the abbreviated MDRD formula. The subjects were stratified according to eGFR≥90 ml×min(-1)·(1.73 m2)(-1), 60≤eGFR<90 ml×min(-1)·(1.73 m2)(-1) and eGFR<60 ml×min(-1)·(1.73 m2)(-1) and followed up for 180 days. Death, myocardial infarction or stroke was regarded as the primary end point. RESULTS: Incidence of the primary end point was 6.3% at eGFR≥90 ml×min(-1)(1.73 m2)(-1), 10.1% at 60≤eGFR<90 ml×min(-1)·(1.73 m2)(-1) and 15.5% at eGFR<60 ml×min(-1)·(1.73 m2)(-1) (P=0.032). The 180 day mortality was 1.9% at eGFR≥90 ml×min(-1) (1.73 m2)(-1), 2.6% at 60≤eGFR<90 ml×min(-1)·(1.73 m2)(-1) and 9.1% at eGFR<60 ml×min(-1)·(1.73 m2)(-1) (P=0.01). In a logistic regression analysis, adjusting for other important covariables, the delayed intervention remained independently associated with the risk of primary end point in 60≤eGFR<90 ml×min(-1)·(1.73 m2)(-1) group (odds ratio, 2.106 ; 95% confidence interval, 1.102-4.024). CONCLUSION: The strategy of early intervention reduces the risk of death/MI or stroke at 180 days in NSTEACS patients with mild renal dysfunction.

[Gender-based analyses of intervention outcome in non-ST segment elevation acute coronary syndrome].

OBJECTIVE: To investigate the impact of gender on outcomes in patients with non-ST segment elevation acute coronary syndrome undergoing intervention treatment. METHODS: In a multi-center randomized trial, the patients diagnosed as non-ST segment elevation acute coronary syndrome were randomly assigned to undergo early intervention (coronary angiography ≤ 24 h after randomization) or delayed intervention (coronary angiography ≥ 36 h after randomization). The primary outcome was a composite of death, myocardial infarction or stroke at 180 days. The secondary outcomes were death, myocardial infarction, refractory ischemia, stroke or revascularization at 180 days. RESULTS: Among 815 patients (545 males, 270 females), the incidences of primary and secondary outcome were equivalent for both genders (P > 0.05). Males of the early intervention group had a greater incidence of the primary outcome (7.1% vs 14.8%, P = 0.00). The secondary outcome was a composite of death, myocardial infarction or refractory ischemia occurring in 12.5% of males in early intervention group and 21.2% in delayed intervention group. Significant difference existed (P = 0.00). The incidence of another secondary outcome as a composite of death, myocardial infarction, refractory ischemia, stroke or revascularization was equivalent for males in early intervention group and delayed intervention group (26.8% vs 32.4%, P > 0.05). The incidences of primary outcome (12.6% vs 14.3%, P > 0.05) and secondary outcome (18.5% vs 23.5% P > 0.05; 28.5% vs 27.7% P > 0.05) were equivalent for females in early intervention group and delayed intervention group (P > 0.05). CONCLUSION: Patients with non-ST segment elevation acute coronary syndrome undergoing intervention demonstrate no significant gender differences in efficacy and safety. Early intervention reduces the rate of myocardial infarction for males, but it is not superior to delayed intervention for females.

MicroRNA-30e promotes hepatocyte proliferation and inhibits apoptosis in cecal ligation and puncture-induced sepsis through the JAK/STAT signaling pathway by binding to FOSL2.

INTRODUCTION: Hepatocyte proliferation and apoptosis are critical cellular behaviors in rat liver as a result of a liver injury. Herein, we performed this study in order to evaluate the role of miR-30e and its target Fos-Related Antigen-2 (FOSL2) in septic rats through the JAK/STAT signaling pathway. METHODS: Rat models of sepsis were induced by cecal ligation and puncture. Enzyme-linked immunosorbent assay (ELISA) was performed to access serum levels of lipopolysaccharide (LPS), inflammatory factors, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to confirm the successful establishment of the model. The hepatocytes were subject to miR-30e mimics, miR-30e inhibitors or siRNA-FOSL2. The expressions of miR-30e, FOSL2, apoptosis- and, JAK/STAT signaling pathway-related genes in liver tissues and hepatocytes were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. MTT assay and flow cytometry were performed to evaluate hepatocyte viability and apoptosis, respectively. RESULTS: The results obtained revealed that in the septic rats, serum levels of inflammatory factors, LPS, ALT and AST, as well as the expression of FOSL2 were elevated and the JAK/STAT signaling pathway was activated, while there was a reduction in the expression of miR-30e. An initial bioinformatics prediction followed by a confirmatory dual-luciferase reporter assay determined that miR-30e targeted and negatively regulated FOSL2 expression. MiR-30e inhibited the activation of JSK2/STAT3 signaling pathway by reducing FOSL2 expression, while miR-30e enhanced hepatocyte proliferation and decreased hepatocyte cell apoptosis in septic rats. CONCLUSION: These findings indicated that miR-30e may serve as an independent therapeutic target for sepsis, due to its ability to inhibit apoptosis and induce proliferation of hepatocytes by targeted inhibition of FOSL2 through the JAK/STAT signaling pathway.

ABCB1 variants confer susceptibility to primary open-angle glaucoma and predict individual differences to latanoprost treatment.

OBJECTIVE: We investigated whether ABCB1 variants confer susceptibility to primary open-angle glaucoma and predict individual differences to latanoprost treatment. METHODS: Between May 2013 and May 2015, 129 POAG patients enrolled in the Department of Ophthalmology, the Second People's Hospital of Yunnan Province were identified as the case group and 121 healthy individuals were included as the control group. Direct DNA sequencing was used to detect four ABCB1 gene polymorphisms, namely, -129T>C (rs3213619), 1236C>T (rs1128503), 2677G>T/A (rs2032582) and 3435C>T (rs1045642). All POAG patients received latanoprost eye drops once daily. The differences in intraocular pressure (IOP) and visual acuity (VA) before and 1 month after latanoprost treatment were compared in different SNPs genotypes. RESULTS: Statistically significant differences in genotype frequency were found in ABCB1 gene polymorphism 2677G>T/A and 3435C>T between the case group and the control group (both P<0.05). No significant difference in genotype frequency was found in -129T> C and 1236C>T between the two groups (both P>0.05). Importantly, ABCB1 gene 3435C>T polymorphism was associated with a remarkably reduced IOP and an improved VA in POAG patients before and after latanoprost eye drops treatment (both P < 0.05). However, no significant differences in IOP and VA were found in other three genotypes between the two groups (all P>0.05). CONCLUSION: Our results suggest that ABCB1 gene polymorphisms 2677G>T/A and 3435C>T may confer to associated with the susceptibility to POAG. The ABCB1 gene polymorphism 3435C>T may be linked to individual differences in response to latanoprost eye drops treatment in POAG patients.

Tris(2,2'-bipyridyl)ruthenium(II)-Zirconia-Nafion composite modified electrode applied as solid-state electrochemiluminescence detector on electrophoretic microchip for detection of pharmaceuticals of tramadol, lidocaine and ofloxacin.

Tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy)(3)(2+))-Zirconia-Nafion composite modified glassy carbon disk electrode as a solid-state electrochemiluminescence (ECL) detector is successfully applied to an electrophoretic microchip system with a wall-jet configuration. Pharmaceuticals such as tramadol, lidocaine and ofloxacin were selected to characterize the performance of this microchip capillary electrophoresis (CE)-ECL detection system. Voltammetric and ECL behaviors of immobilized Ru(bpy)(3)(2+) were investigated in lidocaine system. Influences of the separation electric field to cyclic voltammograms (CVs) of the immobilized Ru(bpy)(3)(2+) were also investigated. Tramadol, lidocaine and ofloxacin can be baseline separated without any additives. The detection limits (S/N=3) were 2.5x10(-5)molL(-1) for tramadol, 5.0x10(-6)molL(-1) for lidocaine, 1.0x10(-5)molL(-1) for ofloxacin under the sample injection of picoliters, and the linear ranges were from 5.0x10(-5) to 2.5x10(-3)molL(-1) for tramadol, 1.0x10(-5) to 1.0x10(-3)molL(-1) for lidocaine, and 1.0x10(-5) to 2.5x10(-3)molL(-1) for ofloxacin, respectively.