Equilibrative nucleotide transporter ENT3 (SLC29A3): A unique transporter for inherited disorders and cancers.

As a crucial gene associated with diseases, the SLC29A3 gene encodes the equilibrative nucleoside transporter 3 (ENT3). ENT3 plays an essential regulatory role in transporting intracellular hydrophilic nucleosides, nucleotides, hydrophilic anticancer and antiviral nucleoside drugs, energy metabolism, subcellular localization, protein stability, and signal transduction. The mutation and inactivation of SLC29A3 are intimately linked to the occurrence, development, and prognosis of various human tumors. Moreover, many hereditary human diseases, such as H syndrome, pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) syndrome, Faisalabad histiocytosis (FHC), are related to SLC29A3 mutations. This review explores the mechanisms of SLC29A3 mutations and expression alterations in inherited disorders and cancers. Additionally, we compile studies on the inhibition of ENT3, which may serve as an effective strategy to potentiate the anticancer activity of chemotherapy. Thus, the synopsis of genetics, permeant function and drug therapy of ENT3 provides a new theoretical and empirical foundation for the diagnosis, prognosis of evaluation and treatment of various related diseases.

Super-enhancer omics in stem cell.

The hallmarks of stem cells, such as proliferation, self-renewal, development, differentiation, and regeneration, are critical to maintain stem cell identity which is sustained by genetic and epigenetic factors. Super-enhancers (SEs), which consist of clusters of active enhancers, play a central role in maintaining stemness hallmarks by specifically transcriptional model. The SE-navigated transcriptional complex, including SEs, non-coding RNAs, master transcriptional factors, Mediators and other co-activators, forms phase-separated condensates, which offers a toggle for directing diverse stem cell fate. With the burgeoning technologies of multiple-omics applied to examine different aspects of SE, we firstly raise the concept of "super-enhancer omics", inextricably linking to Pan-omics. In the review, we discuss the spatiotemporal organization and concepts of SEs, and describe links between SE-navigated transcriptional complex and stem cell features, such as stem cell identity, self-renewal, pluripotency, differentiation and development. We also elucidate the mechanism of stemness and oncogenic SEs modulating cancer stem cells via genomic and epigenetic alterations hijack in cancer stem cell. Additionally, we discuss the potential of targeting components of the SE complex using small molecule compounds, genome editing, and antisense oligonucleotides to treat SE-associated organ dysfunction and diseases, including cancer. This review also provides insights into the future of stem cell research through the paradigm of SEs.

Trends in cardiovascular risk factor prevalence, treatment, and control among US adolescents aged 12 to 19 years, 2001 to March 2020.

BACKGROUND: Early-life cardiovascular risk factors (CVRFs) are known to be associated with target organ damage during adolescence and premature cardiovascular morbidity and mortality during adulthood. However, contemporary data describing whether the prevalence of CVRFs and treatment and control rates have changed are limited. This study aimed to examine the temporal trends in the prevalence, treatment, and control of CVRFs among US adolescents over the past 2 decades. METHODS: This is a serial cross-sectional study using data from nine National Health and Nutrition Examination Survey cycles (January 2001-March 2020). US adolescents (aged 12 to 19 years) with information regarding CVRFs (including hypertension, elevated blood pressure [BP], diabetes, prediabetes, hyperlipidemia, obesity, overweight, cigarette use, inactive physical activity, and poor diet quality) were included. Age-adjusted trends in CVRF prevalence, treatment, and control were examined. Joinpoint regression analysis was performed to estimate changes in the prevalence, treatment, and control over time. The variation by sociodemographic characteristics were also described. RESULTS: A total of 15,155 US adolescents aged 12 to 19 years (representing ≈ 32.4 million people) were included. From 2001 to March 2020, there was an increase in the prevalence of prediabetes (from 12.5% [95% confidence interval (CI), 10.2%-14.9%] to 37.6% [95% CI, 29.1%-46.2%]) and overweight/obesity (from 21.1% [95% CI, 19.3%-22.8%] to 24.8% [95% CI, 21.4%-28.2%]; from 16.0% [95% CI, 14.1%-17.9%] to 20.3% [95% CI, 17.9%-22.7%]; respectively), no improvement in the prevalence of elevated BP (from 10.4% [95% CI, 8.9%-11.8%] to 11.0% [95% CI, 8.7%-13.4%]), diabetes (from 0.7% [95% CI, 0.2%-1.2%] to 1.2% [95% CI, 0.3%-2.2%]), and poor diet quality (from 76.1% [95% CI, 74.0%-78.2%] to 71.7% [95% CI, 68.5%-74.9%]), and a decrease in the prevalence of hypertension (from 8.1% [95% CI, 6.9%-9.4%] to 5.5% [95% CI, 3.7%-7.3%]), hyperlipidemia (from 34.2% [95% CI, 30.9%-37.5%] to 22.8% [95% CI, 18.7%-26.8%]), cigarette use (from 18.0% [95% CI, 15.7%-20.3%] to 3.5% [95% CI, 2.0%-5.0%]), and inactive physical activity (from 83.0% [95% CI, 80.7%-85.3%] to 9.5% [95% CI, 4.2%-14.8%]). Sex and race/ethnicity affected the evolution of CVRF prevalence differently. Whilst treatment rates for hypertension and diabetes did not improve significantly (from 9.6% [95% CI, 3.5%-15.8%] to 6.0% [95% CI, 1.4%-10.6%]; from 51.0% [95% CI, 23.3%-78.7%] to 26.5% [95% CI, 0.0%-54.7%]; respectively), BP control was relatively stable (from 75.7% [95% CI, 56.8%-94.7%] to 73.5% [95% CI, 40.3%-100.0%]), while glycemic control improved to a certain extent, although it remained suboptimal (from 11.8% [95% CI, 0.0%-31.5%] to 62.7% [95% CI, 62.7%-62.7%]). CONCLUSIONS: From 2001 to March 2020, although prediabetes and overweight/obesity increased, hypertension, hyperlipidemia, cigarette use, and inactive physical activity decreased among US adolescents aged 12 to 19 years, whereas elevated BP, diabetes, and poor diet quality remained unchanged. There were disparities in CVRF prevalence and trends across sociodemographic subpopulations. While treatment and control rates for hypertension and diabetes plateaued, BP control were stable, and improved glycemic control was observed.

Ceftazidime/avibactam versus polymyxin B in carbapenem-resistant Klebsiella pneumoniae infections: a propensity score-matched multicenter real-world study.

OBJECTIVES: In this retrospective observational multicenter study, we aimed to assess efficacy and mortality between ceftazidime/avibactam (CAZ/AVI) or polymyxin B (PMB)-based regimens for the treatment of Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections, as well as identify potential risk factors. METHODS: A total of 276 CRKP-infected patients were enrolled in our study. Binary logistic and Cox regression analysis with a propensity score-matched (PSM) model were performed to identify risk factors for efficacy and mortality. RESULTS: The patient cohort was divided into PMB-based regimen group (n = 98, 35.5%) and CAZ/AVI-based regimen group (n = 178, 64.5%). Compared to the PMB group, the CAZ/AVI group exhibited significantly higher rates of clinical efficacy (71.3% vs. 56.1%; p = 0.011), microbiological clearance (74.7% vs. 41.4%; p < 0.001), and a lower incidence of acute kidney injury (AKI) (13.5% vs. 33.7%; p < 0.001). Binary logistic regression revealed that the treatment duration independently influenced both clinical efficacy and microbiological clearance. Vasoactive drugs, sepsis/septic shock, APACHE II score, and treatment duration were identified as risk factors associated with 30-day all-cause mortality. The CAZ/AVI-based regimen was an independent factor for good clinical efficacy, microbiological clearance, and lower AKI incidence. CONCLUSIONS: For patients with CRKP infection, the CAZ/AVI-based regimen was superior to the PMB-based regimen.

Prediction of miRNA-disease associations by neural network-based deep matrix factorization.

MicroRNA(miRNA) is a class of short non-coding RNAs with a length of about 22 nucleotides, which participates in various biological processes of cells. A number of studies have shown that miRNAs are closely related to the occurrence of cancer and various human diseases. Therefore, studying miRNA-disease associations is helpful to understand the pathogenesis of diseases as well as the prevention, diagnosis, treatment and prognosis of diseases. Traditional biological experimental methods for studying miRNA-disease associations have disadvantages such as expensive equipment, time-consuming and labor-intensive. With the rapid development of bioinformatics, more and more researchers are committed to developing effective computational methods to predict miRNA-disease associations in roder to reduce the time and money cost of experiments. In this study, we proposed a neural network-based deep matrix factorization method named NNDMF to predict miRNA-disease associations. To address the problem that traditional matrix factorization methods can only extract linear features, NNDMF used neural network to perform deep matrix factorization to extract nonlinear features, which makes up for the shortcomings of traditional matrix factorization methods. We compared NNDMF with four previous classical prediction models (IMCMDA, GRMDA, SACMDA and ICFMDA) in global LOOCV and local LOOCV, respectively. The AUCs achieved by NNDMF in two cross-validation methods were 0.9340 and 0.8763, respectively. Furthermore, we conducted case studies on three important human diseases (lymphoma, colorectal cancer and lung cancer) to validate the effectiveness of NNDMF. In conclusion, NNDMF could effectively predict the potential miRNA-disease associations.

Personalized application of antimicrobial drugs in pediatric patients with augmented renal clearance: a review of literature.

The effect of renal functional status on drug metabolism is a crucial consideration for clinicians when determining the appropriate dosage of medications to administer. In critically ill patients, there is often a significant increase in renal function, which leads to enhanced drug metabolism and potentially inadequate drug exposure. This phenomenon, known as augmented renal clearance (ARC), is commonly observed in pediatric critical care settings. The findings of the current study underscore the significant impact of ARC on the pharmacokinetics and pharmacodynamics of antimicrobial drugs in critically ill pediatric patients. Moreover, the study reveals a negative correlation between increased creatinine clearance and blood concentrations of antimicrobial drugs. The article provides a comprehensive review of ARC screening in pediatric patients, including its definition, risk factors, and clinical outcomes. Furthermore, it summarizes the dosages and dosing regimens of commonly used antibacterial and antiviral drugs for pediatric patients with ARC, and recommendations are made for dose and infusion considerations and the role of therapeutic drug monitoring. CONCLUSION:  ARC impacts antimicrobial drugs in pediatric patients. WHAT IS KNOWN: • ARC is inextricably linked to the failure of antimicrobial therapy, recurrence of infection, and subtherapeutic concentrations of drugs. WHAT IS NEW: • This study provides an updated overview of the influence of ARC on medication use and clinical outcomes in pediatric patients. • In this context, there are several recommendations for using antibiotics in pediatric patients with ARC: 1) increase the dose administered; 2) prolonged or continuous infusion administration; 3) use of TDM; and 4) use alternative drugs that do not undergo renal elimination.

Development and validation of an automatic machine learning model to predict abnormal increase of transaminase in valproic acid-treated epilepsy.

Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy for 1995 epilepsy patients. The study employed the two-tailed T test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using "H2O" autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance.

Effects of Fe-N co-modified biochar on methanogenesis performance, microbial community, and metabolic pathway during anaerobic co-digestion of alternanthera philoxeroides and cow manure.

The performance of anaerobic digestion (AD) is susceptible to disturbances in feedstock degradation, intermediates accumulation, and methanogenic archaea activity. To improve the methanogenesis performance of the AD system, Fe-N co-modified biochar was prepared under different pyrolysis temperatures (300,500, and 700 °C). Meanwhile, pristine and Fe-modified biochar were also derived from alternanthera philoxeroides (AP). The aim was to compare the effects of Fe-N co-modification, Fe modification, and pristine biochar on the methanogenic performance and explicit the responding mechanism of the microbial community in anaerobic co-digestion (coAD) of AP and cow manure (CM). The highest cumulative methane production was obtained with the addition of Fe-N-BC500 (260.38 mL/gVS), which was 42.37 % higher than the control, while the acetic acid, propionic acid, and butyric acid concentration of Fe-N-BC were increased by 147.58 %, 44.25 %, and 194.06 % compared with the control, respectively. The co-modified biochar enhanced the abundance of Chloroflexi and Methanosarcina in the AD system. Metabolic pathway analysis revealed that the increased methane production was related to the formation and metabolism of volatile fatty acids and that Fe-N-BC500 enhanced the biosynthesis of coenzyme A and the cell activity of microorganisms, accelerating the degradation of propionic acid and enhancing the hydrogenotrophic methanogenesis pathway. Overall, Fe-N co-modified biochar was proved to be an effective promoter for accelerated methane production during AD.

Farnesoid X receptor is inhibited after ileum transposition in diabetic rats: its hypoglycemic effect.

Background: Aim to investigate bile acid profile changes and the Farnesoid X receptor (FXR) status after ileotransposition (IT), and reveal its possible hypoglycemic mechanism. Methods: Twenty male diabetic rats were randomly assigned into the IT group and the sham IT (SH) group. Bile acid profiles were measured using an ultra-performance liquid chromatography-tandem mass spectrometry. Glucose metabolism was monitored after oral administration of FXR inhibitor and agonist. And the expression of key FXR target genes were measured. Results: The levels of ß-muricholic acid (P = 0.047), tauro-α-muricholic acid and tauro-ß-muricholic acid (P < 0.001) in plasma in the IT group were higher than those in the SH group, and the levels of taurocholic acid (P = 0.049) and turoursodeoxycholic acid (P = 0.030) were lower than those in the SH group. After inhibition of intestinal FXR, the glucose metabolism in the SH group was improved. When FXR agonist was given, the blood glucose level was increased in both groups. After sacrifice, the levels of glycoursodeoxycholic acid, tauro-α-muricholic acid and tauro-ß-muricholic acid in liver and ileum tissues were higher than those in the SH group (P < 0.05), the level of α- muricholic acid (P < 0.001) in liver tissues were lower than that in the SH group. Moreover, the expression of CYP7A1 mRNA (P < 0.001) and FGF15 mRNA (P = 0.001) in the IT group was significantly higher, and the expression of PEPCK mRNA (P = 0.004), SREPB1c mRNA (P = 0.005) and SRB1 mRNA (P = 0.001) were significantly lower than that in the SH group. Conclusions: We demonstrate a remarkable heterogeneity of BA profiles after IT, FXR activation might has a detrimental effect on glucose metabolism.

Low lean mass with obesity in older adults with hypertension: prevalence and association with mortality rate.

BACKGROUND: The influence of sarcopenic obesity (SO) on overall survival in older adults with hypertension has not been addressed. The aim of this study was to investigate the prevalence and mortality predictive value of various body composition phenotypes, focusing mainly on SO, in older adults with hypertension. METHODS: We included 1105 hypertensive patients aged ≥ 60 years from the National Health and Nutrition Examination Survey 1999-2004. Sarcopenia was broadly defined based on low lean mass (LLM; as measured by dual-energy X-ray absorptiometry), and was defined using appendicular lean mass (ALM) divided by height squared (ALM/height2), weight (ALM/weight), and body mass index (BMI; ALM/BMI), respectively. Obesity was defined as BMI ≥ 30 kg/m2, body fat percentage ≥ 30/42%, or waist circumference ≥ 102/88 cm. The prevalence of LLM with obesity was estimated according to each ALM index (ALMI). Multivariable Cox regression analysis and sensitivity analysis were used to examine the association between various body composition phenotypes and all-cause mortality. RESULTS: In older adults with hypertension, the prevalence of LLM with obesity by the ALM/height2 index (9.8%) was lower relative to the ALM/weight (11.7%) and ALM/BMI indexes (19.6%). After a median follow-up of 15.4 years, 642 deaths occurred. In the fully adjusted models, LLM with obesity was significantly associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.14-2.49, P = 0.008; HR 1.48, 95% CI 1.04-2.10, P = 0.028; HR 1.30, 95% CI 1.02-1.66, P = 0.037; respectively) compared with the normal body phenotype, with no statistical differences found in individuals with LLM or obesity alone. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: The prevalence of LLM with obesity markedly differed in older adults with hypertension according to the 3 different ALMIs, varying from 9.8%, 11.7%, to 19.6%. Patients with both LLM and obesity had a higher risk of all-cause mortality. Further large, prospective, cohort studies are warranted to validate these findings and uncover underlying mechanisms.

Room-Temperature Synthesis of Carbon-Nanotube-Interconnected Amorphous NiFe-Layered Double Hydroxides for Boosting Oxygen Evolution Reaction.

The oxygen evolution reaction (OER) is a key half-reaction in electrocatalytic water splitting. Large-scale water electrolysis is hampered by commercial noble-metal-based OER electrocatalysts owing to their high cost. To address these issues, we present a facile, one-pot, room-temperature co-precipitation approach to quickly synthesize carbon-nanotube-interconnected amorphous NiFe-layered double hydroxides (NiFe-LDH@CNT) as cost-effective, efficient, and stable OER electrocatalysts. The hybrid catalyst NiFe-LDH@CNT delivered outstanding OER activity with a low onset overpotential of 255 mV and a small Tafel slope of 51.36 mV dec-1, as well as outstanding long-term stability. The high catalytic capability of NiFe-LDH@CNT is associated with the synergistic effects of its room-temperature synthesized amorphous structure, bi-metallic modulation, and conductive CNT skeleton. The room-temperature synthesis can not only offer economic feasibility, but can also allow amorphous NiFe-LDH to be obtained without crystalline boundaries, facilitating long-term stability during the OER process. The bi-metallic nature of NiFe-LDH guarantees a modified electronic structure, providing additional catalytic sites. Simultaneously, the highly conductive CNT network fosters a nanoporous structure, facilitating electron transfer and O2 release and enriching catalytic sites. This study introduces an innovative approach to purposefully design nanoarchitecture and easily synthesize amorphous transition-metal-based OER catalysts, ensuring their cost effectiveness, production efficiency, and long-term stability.

Genetic screening in patients of Meige syndrome and blepharospasm.

OBJECTIVE: Meige syndrome (MS) is cranial dystonia, including bilateral eyelid spasms (blepharospasm; BSP) and involuntary movements of the jaw muscles (oromandibular dystonia; OMD). Up to now, the pathogenic genes of MS and BSP are still unclear. METHODS: We performed Sanger sequencing of GNAL, TOR1A, TOR2A, THAP1, and REEP4 exons on 78 patients, including 53 BSP and 25 MS and 96 healthy controls. RESULTS: c.845G > C[R282P] of TOR1A, c.629delC[p.Gly210AlafsTer60] of TOR2A, c.1322A > G[N441S] of GNAL, c.446G > A[R149Q], and c.649C > T[R217C] of REEP4 were identified and predicated as deleterious probably damaging variants. Three potential alterations of splicing variants of TOR1A and TOR2A were identified in patients. The frequencies of TOR1A rs1435566780 and THAP1 rs545930392 were higher in patients than in controls. CONCLUSIONS: TOR1A rs1435566780 (c.*16G > C(G > A)) and THAP1 rs545930392 (c.192G > A[K64K]) may contribute to the etiology of MS and BSP. Other identified rare mutations predicted as deleterious probably damaging need further confirmation. Larger MS and BSP cohorts and functional studies will need to be performed further to elucidate the association between these genes and the diseases.

Management Strategy for Gallbladder Polypoid Lesions: Results of a 5-Year Single-Center Cohort Study.

INTRODUCTION: Controversy remains about the classification, differential diagnosis, and treatment strategy for gallbladder polypoid lesions (GPLs). This study sought to explore the individualized treatment strategy for GPLs. METHODS: We retrospectively studied 642 consecutive patients with GPLs from January 2015 to May 2020. Univariate and multivariable analyses were performed to explore the potential risk factors for neoplastic polyps. The outcome of laparoscopic gallbladder-preserving polypectomy (GPP) was evaluated and compared with that of laparoscopic cholecystectomy (LC). RESULTS: Of 642 enrolled patients, 572 underwent LC, and 70 underwent GPP. Pathologically, the majority of GPLs were cholesterol polyps (68.4%), followed by adenomyomatosis (19.9%), benign adenoma (7.3%), adenocarcinoma (3.6%), and rare pathological types (0.8%). Additionally, 66.3% (379/572) of the LC cases were classified as non-neoplastic, and 33.7% (193/572) neoplastic polyps. Multivariate analysis demonstrated that single polyps (OR 1.956, 95% CI: 1.121-3.412; p = 0.018), polyps located at the gallbladder fundus (OR 4.326, 95% CI: 2.179-8.591; p < 0.001), polyps not less than 14 mm (OR 2.833, 95% CI: 1.614-4.973; p < 0.001), and polyps with a broad base (OR 4.173, 95% CI: 1.743-9.990; p = 0.001) were independent risk factors for neoplastic polyps. The 5-year prospective results after GPP showed that the 1-year and 3-year polyp recurrence rates were 13.2% and 23.4%, respectively. CONCLUSION: The majority of GPLs are cholesterol or other benign lesions without malignant potential. LC is the main treatment procedure for GPLs with a high neoplastic risk. GPP is potentially feasible and could be an alternative management strategy for a group of GPLs patients who meet the selection criteria.

His-Purkinje conduction system pacing: A systematic review and network meta-analysis in bradycardia and conduction disorders.

BACKGROUND: His-Purkinje conduction system pacing (HPCSP) has emerged as an effective alternative to overcome the limitations of right ventricular pacing (RVP) via physiological left ventricular activation, but there remains a paucity of comparative information for His bundle pacing (HBP) and left bundle branch pacing (LBBP). METHODS: A Bayesian random-effects network analysis was conducted to compare the relative effects of HBP, LBBP, and RVP in patients with bradycardia and conduction disorders. PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from database inception until September 21, 2021. RESULTS: Twenty-eight studies involving 4160 patients were included in this meta-analysis. LBBP significantly improved success rate, pacing threshold, pacing impedance, and R-wave amplitude compared with HBP. LBBP also demonstrated a nonsignificant trend towards superior outcomes of lead complications, heart failure hospitalization, atrial fibrillation, and all-cause death. However, HBP was associated with significantly shorter paced QRS duration relative to LBBP. Despite higher success rates, shorter procedure/fluoroscopy duration, and fewer lead complications, patients receiving RVP were more likely to experience reduced left ventricular ejection fraction, longer paced QRS duration, and higher rates of heart failure hospitalization than those receiving HPCSP. No statistical differences were observed in the remaining outcome measures. CONCLUSIONS: This network meta-analysis demonstrates the efficacy and safety of HPCSP for the treatment of bradycardia and conduction disorders, with differences in pacing parameters, electrophysiology characteristics, and clinical outcomes between HBP and LBBP. Larger-scale, long-term comparative studies are warranted for further verification.

Comparative effectiveness of Lopinavir/Ritonavir-based regimens in COVID-19.

The coronavirus disease 2019 (COVID-19) is an epidemic disease caused by the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) and spreading throughout the world rapidly. Here we evaluated the efficacy of the Lopinavir/Ritonavir (LPV/r) and its combination with other drugs in the treatment of COVID-19. We included 170 confirmed COVID-19 patients who had been cured and discharged. Their antiviral therapies were LPV/r alone or combinations with interferon (IFN), Novaferon and Arbidol. We evaluated the medication efficacy by comparing the time of the negative nucleic acid conversion and the length of hospitalization mainly. The LPV/r + Novaferon [6.00 (4.00-8.00) and 7.50 (5.00-10.00) days] had shorter time of the negative nucleic acid conversion (P = .0036) and shorter time of hospitalization (P < .001) compared with LPV/r alone [9.00 (5.00-12.00) and 12.00 (11.00-15.00) days] and LPV/r + IFN [9.00 (7.25-11.00) and 12.00 (10.00-13.50) days]. On the contrary, LPV/r + IFN [9.00 (7.25-11.00) and 12.00 (10.00-13.50) days] had shorter time of the negative nucleic acid conversion (P = .031) and shorter time of hospitalization (P < .001) compared with LPV/r + IFN +Novaferon [10.00 (8.00-11.25) and 13.50 (11.50-17.00) days] and LPV/r + IFN +Arbidol [14.00 (9.75-19.00) and 19.50 (13.25-24.00) days]. In conclusion, the combination of LPV/r and Novaferon may have better efficacy against COVID-19. However, adding IFN based on LPV/r + Novaferon or adding Arbidol based on LPV/r + IFN may not improve the efficacy.

[Risk Factors for Surgical Site Infection after Conversion from Laparoscopic to Open Cholecystectomy].

Objective To investigate the incidence of surgical site infection(SSI)following conversion from laparoscopic to open cholecystectomy and to analyze the related risk factors. Methods The clinical data of 179 patients who had experienced conversion from laparoscopic to open cholecystectomy in Peking Union Medical College Hospital from January 2014 to August 2019 were analyzed retrospectively.Univariate and multivariate logistic regression analyses were performed to evaluate the associations between clinical variables and SSI. Results The incidence of SSI was 19.0%(34/179)after conversion from laparoscopic to open cholecystectomy.The multivariable analysis demonstrated that preoperative endoscopic retrograde cholangiopancreatography(ERCP)(OR=4.208,95% CI:1.590-11.135,P=0.004)was the only independent risk factor of SSI. Conclusions The incidence of SSI after conversion from laparoscopic to open cholecystectomy increased remarkably,especially in those who had preoperative ERCP.Preventive interventions should be taken to reduce the incidence of SSI.

Neutrophil-Lymphocyte Ratio in Predicting Infective Endocarditis: A Case-Control Retrospective Study.

BACKGROUND: Infective endocarditis (IE) is a complex infectious disease with high morbidity and mortality. The inflammation mechanism of IE is a complex network including interactions of inflammatory cytokines and other components of host response. As an important inflammation marker, the prediction ability of neutrophil-to-lymphocyte ratio (NLR) in IE deserves further investigation. METHODS: NLR values were measured and compared between IE patients and healthy controls, good and bad clinical outcome groups. The receiver operating characteristic curves (ROCs) of NLR and cut-off values were measured in IE patients, pathogen-subgroups, and different clinical outcome groups. RESULTS: There were 678 IE patients and 2520 healthy controls enrolled in our study. The number of good and bad clinical outcome patients was 537 and 141, respectively. The value of NLR was significantly higher in IE patients than healthy controls (6.29 ± 9.36 vs. 1.87 ± 0.34, p < 0.001), and the area under the ROC (AUC) was 0.817 (95% CI (0.794, 0.839), p < 0.001). The critical value of NLR for diagnosis of IE was 2.68, with a sensitivity of 69%, and a specificity of 88%. The value of NLR was significantly higher in bad clinical outcome patients than in good clinical outcome patients (5.8 ± 6.02 vs. 3.62 ± 2.61, p < 0.001). The critical value of NLR to predict the outcome of IE was 5.557, with a sensitivity of 39.0% and a specificity of 85.3%. CONCLUSIONS: NLR is a predictive marker for IE patients, especially in Gram-negative bacteria and Gram-positive bacteria-infected IE patients. NLR also can predict the outcome of IE. Early detecting NLR upon admission may assist in early diagnosis and risk stratification of patients with IE.

miR-221 participates in the airway epithelial cells injury in asthma via targeting SIRT1.

AIM OF THE STUDY: To investigate the role of microRNA-221 (miR-221) in the airway epithelial cell injury in asthma and delineate the underlying mechanism that may involve with SIRT1. MATERIALS AND METHOD: Bronchial epithelial cells from asthma patients and healthy controls were obtained by bronchoscopic brushing. The miR-221 and SIRT1 mRNA level in collected cells were detected by qRT-CPR. BEAS2B cell lines were cultured in vitro. In order to up-regulate miR-221 and SIRT1, miR-221 mimic and pcDNA3.1-SIRT1 vector was transfected into BEAS2B cells, respectively. The expression changes of miR-221 and SIRT1 after transfection was observed by qRT-PCR and Western blot. The target relationship between miR-221 and SIRT1 was confirmed using dual-luciferase reporter assay.The cell viability changes after transfection was measured using cellTiter-blue reagent. The apoptosis rate was detected by flow cytometry. RESULT: Compared with healthy controls, miR-221 expression significantly increased in bronchial epithelial cells from patients subjects. In contrast, the level of SIRT1 mRNA reduced in the bronchial epithelial cell from asthma patients. In vitro, up-regulation of miR-221 could inhibit the expression of SIRT1 both at mRNA and protein level in BEAS2B cells. A negative correlation between miR-221 and SIRT1 mRNA in samples from patients was confirmed and dual-luciferase reporter assay showed that miR-221 directly binds to the 3'UTR of SIRT1 mRNA. Overexpression of miR-221 or SIRT1 knockdown could inhibit proliferation but induce apoptosis in BEAS2B cells. Moreover, up-regulation of SIRT1 could antagonize miR-221's inhibitory effect. CONCLUSION: miR-221 may participate in the airway epithelial cells injury in asthma via targeting SIRT1.

Prognostic Value of ALT, AST, and AAR in Hepatocellular Carcinoma with B-Type Hepatitis-Associated Cirrhosis after Radical Hepatectomy.

BACKGROUND: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and AST to ALT ratio (AAR) were shown to be associated with prognosis in some groups of hepatocellular carcinoma (HCC). However, their clinicopathologic and prognostic roles in HCC patients with B-type hepatitis-associated cirrhosis (HBAC) have not been comprehensively investigated. The present study aimed to address the issues. METHODS: A total of 125 patients with HCC and HBAC after radical hepatectomy were included. The correlations of ALT, AST, and AAR with clinicopathologic parameters, overall/recurrence-free survival, overall/early recurrence, and post-recurrence survival were evaluated using univariate and multivariate analyses. RESULTS: ALT and AST, which positively correlated with each other, had significant relationships with tumornode-metastasis (TNM) stage and Edmondson-Steiner grade. In univariate analyses, ALT and AST were predictive for early recurrence, overall and recurrence-free survival, while ALT and AST was associated with overall recurrence and post-recurrence survival, respectively. However, only AST was marginally significant in multivariate tests for early recurrence and post-recurrence survival. As for AAR, no significant prognostic relevance was found. CONCLUSIONS: Our data suggest that ALT and AST, but not AAR, might be potential predictors of post-resectional outcome in HCC with HBAC. These effects might depend on their associations with crucial clinicopathologic variables.