Comprehensive meta-analysis of the effects of oral medroxyprogesterone acetate plus conjugated equine oestrogens on the lipid profile in women: Insights from randomized controlled trials.

BACKGROUND: Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively. RESULTS: A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = -11.93 mg/dL; 95% CI: -13.42, -10.44; p < .001) and LDL-C (WMD = -16.61 mg/dL; 95% CI: -17.97, -15.26; p < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG). CONCLUSIONS: MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT.

Whole-genome sequencing of clinical isolates of Citrobacter Europaeus in China carrying blaOXA-48 and blaNDM-1.

OBJECTIVE: To analyze the clinical infection characteristics and genetic environments of resistance genes in carbapenem-resistant Citrobacter europaeus using whole-genome sequencing. METHODS: The susceptibility of two clinical isolates of C. europaeus (WF0003 and WF1643) to 24 antimicrobial agents was assessed using the BD Phoenix™ M50 System and Kirby-Bauer (K-B) disk-diffusion method. Whole-genome sequencing was performed on the Illumina and Nanopore platforms, and ABRicate software was used to predict resistance and virulence genes of carbapenem-resistant C. europaeus. The characteristics of plasmids carrying carbapenem-resistance genes and their genetic environments were analyzed. Single nucleotide polymorphisms were used to construct a phylogenetic tree to analyze the homology of these two C. europaeus strains with ten strains of C. europaeus in the NCBI database. RESULTS: The two strains of carbapenem-resistant C. europaeus are resistant to various antimicrobial agents, particularly carbapenems and ß-lactams. WF0003 carries blaNDM- 1, which is located on an IncX3 plasmid that has high homology to the pNDM-HN380 plasmid. blaNDM- 1 is located on a truncated Tn125. It differs from Tn125 by the insertion of IS5 in the upstream ISAba125 and the deletion of the downstream ISAba125, which is replaced by IS26. WF1643 carries blaOXA- 48 in a Tn1999 transposon on the IncL/M plasmid, carrying only that single drug resistance gene. Homology analysis of these two strains of C. europaeus with ten C. europaeus strains in the NCBI database revealed that the 12 strains can be classified into three clades, with both WF0003 and WF1643 in the B clade. CONCLUSION: To the best of our knowledge, this is the first study to report an IncX3 plasmid carrying blaNDM- 1 in C. europaeus in China. C. europaeus strains harboring carbapenem-resistance genes are concerning in relation to the spread of antimicrobial resistance, and the presence of carbapenem-resistance genes in C. europaeus should be continuously monitored.

PCSK9 inhibitor recaticimab for hypercholesterolemia on stable statin dose: a randomized, double-blind, placebo-controlled phase 1b/2 study.

BACKGROUND: Recaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. This study aimed to further assess the efficacy and safety of recaticimab in patients with hypercholesterolemia. METHODS: In this randomized, double-blind, placebo-controlled phase 1b/2 trial, patients receiving stable dose of atorvastatin with an LDL-C level of 2.6 mmol/L or higher were randomized in a ratio of 5:1 to subcutaneous injections of recaticimab or placebo at different doses and schedules. Patients were recruited in the order of 75 mg every 4 weeks (75Q4W), 150Q8W, 300Q12W, 150Q4W, 300Q8W, and 450Q12W. The primary endpoint was percentage change in LDL-C from the baseline to end of treatment (i.e., at week 16 for Q4W and Q8W schedule and at week 24 for Q12W schedule). RESULTS: A total of 91 patients were enrolled and received recaticimab and 19 received placebo. The dose of background atorvastatin in all 110 patients was 10 or 20 mg/day. The main baseline LDL-C ranged from 3.360 to 3.759 mmol/L. The least-squares mean percentage reductions in LDL-C from baseline to end of treatment relative to placebo for recaticimab groups at different doses and schedules ranged from -48.37 to -59.51%. No serious treatment-emergent adverse events (TEAEs) occurred. The most common TEAEs included upper respiratory tract infection, increased alanine aminotransferase, increased blood glucose, and increased gamma-glutamyltransferase. CONCLUSION: Recaticimab as add-on to moderate-intensity statin therapy significantly and substantially reduced the LDL-C level with an infrequent administration schedule (even given once every 12 weeks), compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov , number NCT03944109.

miR-3178 as a prognostic indicator and tumor suppressor of gastric cancer.

BACKGROUND: Gastric cancer is a common malignant tumor with an increasing death rate. MicroRNA can serve as a promising biomarker for the progression and prognosis of various cancers. AIMS: The clinical significance and biological function of miR-3178 in gastric cancer was assessed in this study. METHODS: A total of 117 paired tissues were collected from gastric cancer patients. Quantitative real-time polymerase chain reaction was used to detect the expression of miR-3178 in gastric cancer tissues and cells. The association between miR-3178 expression and the clinicopathological features of patients were analyzed by χ2 test. Kaplan-Meier analysis and Cox regression were employed to investigate the prognostic value of miR-3178. Finally, the effect of miR-3178 on the cellular process of gastric cancer was investigated by CCK-8 and transwell assay. RESULTS: miR-3178 was downregulated in gastric cancer tissues and cells, which showed a significant association with the TNM stage and lymph node metastasis of patients and a poor prognosis. MiR-3178 and TNM stage were considered as two independent prognostic factors for gastric cancer. Furthermore, the downregulation of miR-3178 promoted cell proliferation, migration, and invasion of gastric cancer by regulating Notch1. CONCLUSION: miR-3178 may be involved in the progression of gastric cancer, which provides new insights into the treatment of gastric cancer.

Changing Pain Management Strategy from Opioid-centric Towards Improve Postoperative Cognitive Dysfunction with Dexmedetomidine.

OBJECTIVE: This study was aimed to investigate the effectiveness of dexmedetomidine (DEX) on improving the level of pain and disability to find out the possible correlation between psychological factors with pain management satisfaction and physical function in patients with femoral neck fractures. METHODS: One hundred twenty-four adult patients with stable femoral neck fractures (type I and II, Garden classification) who underwent internal fixation, were prospectively enrolled including 62 patients in the DEX group and 62 patients in the control group. The magnitude of disability using Harris Hip Score, Postoperative Cognitive Dysfunction (POCD) using Mini-Mental State Examination (MMSE score), Quality of Recovery (QoR-40), pain-related anxiety (PASS-20), pain management and pain catastrophizing scale (PCS) were recorded on the first and second day after surgery. RESULTS: The DEX group on the first and second days after surgery exhibited higher quality of recovery scores, greater satisfaction with pain management, low disability scores, less catastrophic thinking, lower pain anxiety, greater mini mental state examination scores and less opioid intake and the differences were statistically significant compared with the control group (P<0.001). Emergence agitation and incidence of POCD were significantly less in the DEX group (P<0.001). Decreased disability was associated with less catastrophic thinking and lower pain anxiety, but not associated with more opioid intake (P<0.001). Higher QoR-40 scores had a negative correlation with more catastrophic thinking and more opioid intake (P<0.001). Greater satisfaction with pain management was correlated with less catastrophic thinking and less opioid intake (P<0.001). CONCLUSION: Using DEX as an adjunct to anesthesia could significantly improve postoperative cognitive dysfunction and the quality of recovery and these improvements were accompanied by decrease in pain, emergence agitation, and opioid consumption by DEX administration. Since pain relief and decreased disability were not associated with prescribing greater amounts of opioid intake in the patients, improving psychological factors, including reducing catastrophic thinking or self-efficacy about pain, could be a more effective strategy to reduce pain and disability, meanwhile reducing opioid prescription in the patients. Our findings showed that DEX administration is safe sedation with anti-inflammatory, analgesic and antiemetic effects and it could help change pain management strategy from opioidcentric towards improved postoperative cognitive dysfunction.

Electrocatalytic performance of tyrosinase detection in Penaeus vannamei based on a [(PSS/PPy)(P2Mo18/PPy)5] multilayer composite film modified electrode.

Polyoxometalates (POMs) are widely used in the preparation of sensors that detect the content of substances because of their excellent electron transfer capabilities. In this paper, a [(PSS/PPy)(P2Mo18/PPy)5] multilayer composite film modified electrode was prepared by the potentiostatic deposition method. The electrochemical performance of the modified electrode was studied by cyclic voltammetry under the conditions of different modified layers, different supporting electrolytes and different sweep rates. Different concentrations of tyrosinase were catalyzed by the modified electrode under a suitable supporting electrolyte, and the electrochemical sensing of tyrosinase by the modified electrode was studied. The research results show that the modified electrode has good stability and reproducibility for electrochemical sensing of tyrosinase, and the response current has a good linear relationship with the amount of tyrosinase added. Taking peak III as an example, the detection limit (S/N = 3) was 2.7649 U mL-1. It can be known from the timing ampere curve that as the concentration of tyrosinase in the reaction system continues to increase, its response current increases stepwise, providing a linear curve in the range of 3.66 U mL-1 to 26.87 U mL-1, and the minimum detection limit (S/N = 3) reaches 0.0021 U mL-1. The [(PSS/PPy)(P2Mo18/PPy)5] multilayer composite membrane modified electrode was used to detect tyrosinase in Penaeus vannamei. The spiked recovery of the sample was 96.3-100.8%, indicating that the modified electrode has high accuracy and can be used for the detection of tyrosinase in actual samples.

The Application Value of Serum HE4 in the Diagnosis of Lung Cancer.

Background: To investigate the clinical value of HE4 detection in the diagnosis of lung cancer and the clinical significance of combined detection with CEA, NSE and CYFRA21-1. Methods: 90 cases of lung cancer, 30 cases of pulmonary tuberculosis, 30 cases of pneumonia and 30 cases of health physical examination were selected. The levels of serum HE4, CYFRA21-1, CEA and NSE were detected by electrochemiluminescence method. Statistical analysis was performed to observe the sensitivity and specificity. Results: The levels of serum HE4, CEA, NSE and CYFRA21-1 in lung cancer group were significantly higher than those in tuberculosis group and health physical examination group. There was no significant difference in the levels of HE4, CEA and NSE between the lung cancer group and the pneumonia group, the difference of CYFRA21-1 level was statistically significant (p<0.05).With health physical examination group as normal controls, the sensitivity and specificity of combined detection of HE4, CEA, NSE and CYFRA21-1 in the diagnosis of lung cancer were 82.2% and 90.0%,and the area under the curve (AUC) was 0.907, followed by HE4 (0.867), CYFRA21-1 (0.787), CEA (0.752) and NSE (0.747). Conclusion: HE4 can be used as a serological marker for the diagnosis of lung cancer. The combined detection of HE4, CEA, NSE and CYFRA21-1 can improve the diagnosis of lung cancer. Serum HE4 levels are highly specific in distinguishing between lung cancer patients and normal population, and are equivalent to CYFRA21-1; but they are less specific than CYFRA21-1 in distinguishing lung cancer patients from pneumonia patients.

Polyoxometalates: Study of inhibitory kinetics and mechanism against α-glucosidase.

Alpha-glucosidase is considered to be an important target for the treatment of noninsulin-dependent diabetes. In this work, the inhibitory effects of polyoxometalates (POMs) affected by three different factors (heteroatom, transition metal substitution element and vanadium substitution number) on α-glucosidase were studied. We found that POMs with Keggin-type and vanadium-substituted Dawson-type structures act as effective and mostly competitive inhibitors for α-glucosidase (IC50 values around 40-160 µM), and most compounds can compete with the substrate for the active site of α-glucosidase. By analyzing and comparing the inhibitory effects of each series of POMs on α-glucosidase, the results demonstrated that the structure and composition of the POMs themselves may indirect influence on their inhibitory capabilities. Moreover, we gained initial information about the structure-inhibition relationship of different POMs. More intriguingly, molecular docking simulation suggested that all compounds bind into the active site of α-glucosidase by multiple van-der-Waals and hydrogen bond interactions. Our kinetic data demonstrate the considerable potential of POMs for the development of clinically valuable α-glucosidase inhibitors.

Room-Temperature CuI-Catalyzed Amination of Aryl Iodides and Aryl Bromides.

A general and effective CuI/N',N'-diaryl-1H-pyrrole-2-carbohydrazide catalyst system was developed for the amination of aryl iodides and bromides at room temperature with good chemoselectivity between -OH and -NH2 groups. Only 5 mol % of CuI and ligands was needed in this protocol to effect the amination of various aryl bromides and aryl iodides with a wide range of aliphatic and aryl amines (1.3 equiv).

[Biomechanical analysis on healing process of sagittal fracture of the mandibular condyle after rigid fixation].

PURPOSE: To analyze the biomechanical healing process on rigid fixation of sagittal fracture of the mandibular condyle (SFMC), and to provide guidelines for surgical treatment. METHODS: Three-dimensional finite element model (3D-FEAM) of mandible and condyle was established. The right condyle was simulated as SFMC with 0.1 mm space across the condyle length ways. The 3D-FEAM of rigid fixation was established. The biomechanical factors such as stress distribution of condylar surface, displacement around fracture, stress on the plate and stress shielding were calculated during 0, 4, 8 and 12-week after rigid fixation. RESULTS: The maximum equivalent stress of normal condyle was located at the area of middle 1/3 of condylar neck. The maximum equivalent stress at 0-week after fixation was 23 times than that on normal condyle. They were located at the condylar stump and the plate near inferior punctual areas of fracture line. There were little stress on the other areas. The maximum equivalent stress at 4, 8 and 12-week was approximately 6 times than that on normal condyle. They were located at the areas same as the area at 0-week. There were little stress on the other areas at the condyle. The maximum total displacement and maximum total corner were increased 0.57-0.75 mm and 0.01-0.09° respectively during healing process. The maximum equivalent stress at 0-week on the condylar trump was 5-6 times compared with that at 4, 8, and 12-week. The maximum equivalent stress, maximum total displacement and maximum total corner on the fractured fragment were not changed significantly during healing process. The maximum equivalent stress at 0-week on the plate was 7-9 times compared with that at 4, 8, 12-week. CONCLUSIONS: The stress of the condyle and stress shielding of the plate may be the reasons of absorbing and rebuilding on the condyle in healing process of SFMC. The biomechanical parameters increase obviously at 4-week after fixation. Elastic intermaxillary traction is necessary to decrease total displacement and total corner of the condyle, and liquid diet is necessary to decrease equivalent stress within 4 weeks. Rehabilitation training should be used to recover TMJ functions after 4 weeks because the condyle and mandible have the ability to carry out normal functions.

[Effects of delayed opening of infarct-related artery on late left ventricular remodeling in patients with acute anterior myocardial infarction].

OBJECTIVE: To assess the effect of delayed opening of the infarct-related artery (IRA) by percutaneous coronary intervention (PCI) on the late left ventricular remodeling after acute anterior myocardial infarction (AAMI). METHODS: Sixty four patients with initial Q-wave AAMI and with the total occluded IRA conformed by angiogram at 9.1 +/- 2.3 (2 - 14) days after the onset were divided into successful PCI group and control group (not receiving PCI or the IRA not re-opened). Two-D echocardiogram was performed at acute phase (about 3 weeks), 2 and 6 months after onset of AAMI respectively to detect the left ventricular function and left ventricular wall motion abnormality (VWMA). The total congestive heart failure events were recorded during 6 months follow-up. RESULTS: VWMA scores, left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volume indexes (LVEDVI and LVESVI) were similar in 2 groups at acute phase and 2 months after the onset of AAMI. There were no differences between the parameters above at acute phase and 2 months in each group too. VWMA scores and LVEF did not changed significantly at 6 months in each group compared with those at acute phase and 2 months (P > 0.05). But LVEDVI and LVESVI were significantly smaller in the successful PCI group than those in the control group (P < 0.01, P < 0.05). The rate of congestive heart failure events was 19% in control group and 2.0% in successful PCI group (P > 0.05) respectively. CONCLUSIONS: Delayed opening of IRA in AAMI could prevent the late phase but not the early phase of left ventricular remodeling after AMI.