Effect of Continuous Positive Airway Pressure on Blood Pressure in Patients with Resistant Hypertension and Obstructive Sleep Apnea: An Updated Meta-analysis.

PURPOSE OF REVIEW: The effect of continuous positive airway pressure (CPAP) on resistant hypertension in patients at high risk with obstructive sleep apnea (OSA) needs further investigation. We aimed to determine the effect of CPAP on blood pressure in patients with resistant hypertension and OSA. Databases including PubMed, EMBASE, MEDLINE, the Cochrane Library, and CMB were searched. Data were pooled using a random-effects or fixed-effects model to derive weighted mean differences (WMDs) and 95% confidence intervals (CIs). RECENT FINDINGS: A total of 12 trials and 718 participants were included. Compared with control, CPAP significantly reduced 24-h systolic blood pressure (SBP) (WMD: - 5.92 mmHg [ - 8.72, - 3.11]; P＜0.001), 24-h diastolic blood pressure (DBP) (WMD: - 4.44 mmHg [- 6.26 , - 2.62]; P ＜0.001),  daytime SBP (WMD: - 5.76 mmHg [ - 9.16, - 2.36]; P ＜0.001),  daytime DBP (WMD: - 3.92 mmHg [- 5.55, - 2.30];  nighttime SBP (WMD: - 4.87 mmHg [ - 7.96 , - 1.78]; P = 0.002), and nighttime DBP (WMD: - 2.05 mmHg [- 2.99, - 1.11]; P＜0.001) in patients with resistant hypertension and OSA. CPAP improved the blood pressure both in the short (＜3 months) and long term (≥ 3 months). No significant impact on mean heart rate was noted (WMD: -2.76 beats per min [- 7.50, 1.97]; P = 0.25). CPAP treatment was associated with BP reduction in patients with resistant hypertension and OSA.

Effects of Early Versus Delayed Feeding in Patients With Acute Pancreatitis: A Systematic Review and Meta-analysis.

BACKGROUND: The aim of this study was to summarize the optimal strategy for early feeding in patients with acute pancreatitis. METHODS: The search was undertaken in electronic databases, which compared early with delayed feeding in acute pancreatitis. The primary outcome was the length of hospital stay (LOHS). The second outcomes were intolerance of refeeding, mortality, and total cost of each patient. This meta-analysis followed the "Preferred Reporting Items for Systematic Reviews and Meta-analyses" guideline. Research is registered by PROSPERO, CRD42020192133. RESULTS: A total of 20 trials involving 2168 patients were included, randomly assigned to the early feeding group (N = 1033) and delayed feeding group (N = 1135). The LOHS was significantly lower in the early feeding group than the delayed feeding group (mean difference: -2.35, 95% CI: -2.89 to -1.80; P < 0.0001), no matter the mild or severe subgroup ( Pint = 0.69). The secondary outcome of feeding intolerance and mortality were no significant difference (risk ratio: 0.96, 0.40 to 2.16, P = 0.87 and 0.91, 0.57 to 1.46, P = 0.69; respectively). Moreover, the hospitalization cost was significantly less in the early feeding group, resulting in an average savings of 50%. In patients with severe pancreatitis, early feeding after 24 hours may be beneficial ( Pint = 0.001). CONCLUSION: Early oral feeding can significantly reduce the LOHS and hospitalization costs in patients with acute pancreatitis without increasing feeding intolerance or mortality. In patients with severe pancreatitis, early feeding after 24 hours may be beneficial.

Regulation of tumor metastasis and CD8+ T cells infiltration by circRNF216/miR-576-5p/ZC3H12C axis in colorectal cancer.

BACKGROUND: The tumor immune microenvironment (TIME) is an important regulator of tumor progression, growth and metastasis. In addition, tumor metastasis is one of the principal obstacles to the treatment of colorectal cancer (CRC). Circular RNAs (circRNAs) have been recognized as important regulators in the development of malignancies. However, their specific roles and mechanisms in both CRC metastasis and TIME have not been thoroughly investigated. METHODS: High-throughput next-generation sequencing technology and real-time fluorescence quantitative PCR technology were performed to identify differential circRNAs in CRC. Functional assays including transwell assay, wound healing assay, and metastasis models were conducted to assess the effect of circRNF216 on CRC metastasis. In addition, luciferase reporter, western blot, RNA immunoprecipitation (RIP), and fluorescent in situ hybridization (FISH) were performed to explore the underlying mechanism of circRNF216. The level of immune infiltration was assessed by bioinformatics analysis and flow cytometry in CRC model. Furthermore, rescue and mutation experiments were used for verification. RESULTS: circRNF216 was identified as a putative tumor suppressor that is downregulated in CRC tissues and cells. Overexpression of circRNF216 inhibits metastasis in vitro and vivo. Mechanistically, circRNF216 acts as a competitive endogenous RNA (ceRNA) for miR-576-5p, alleviating miR-576-5p repression on its target ZC3H12C, which in turn downregulated N-cadherin. Additionally, circRNF216 could enhance the infiltration level of CD8+ T cells by upregulating ZC3H12C, ultimately inhibiting the development of CRC, which suggests that circRNF216 is a potential biomarker for the treatment of CRC. CONCLUSIONS: Here, we provide novel mechanistic insight revealing how circRNF216 functioned in CRC metastasis and TIME via the circRNF216/miR-576-5p/ZC3H12C pathway. Therefore, circRNF216 holds promise as a potential therapeutic target and novel diagnostic marker for CRC.

Effect of Different Local Antibiotic Regimens on Prevention of Postoperative Infection in Clean Surgical Wounds: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To compare the efficacy of several local antibiotic regimens in preventing surgical site infection (SSI) in clean surgical wounds. DATA SOURCES: The authors searched CNKI (China National Knowledge Infrastructure), the VIP (VIP information resource integration service platform), Wanfang Data knowledge service platform (WANFANG), SinoMed, Cochrane Library, EMBASE, and PubMed. STUDY SELECTION: A total of 20 randomized controlled trials published between January 1, 2000 and April 1, 2021 were included in this meta-analysis. DATA EXTRACTION: Authors extracted the name of the first author, publication date, country, type of surgery, follow-up time, mean age of participants, sample size of each group, interventions, outcome indicators, and study type from each article. DATA SYNTHESIS: The overall effectiveness of eight local managements in reducing the incidence of the SSI effect were compared through the SUCRA (surface under the cumulative ranking curve) probabilities. The results of a network meta-analysis demonstrated that gentamicin ointment (odds ratio [OR], 0.16; 95% CI, 0.04-0.60), mupirocin ointment (OR, 0.44; 95% CI, 0.21-0.94), and gentamicin soaking of the graft (OR, 0.63; 95% CI, 0.44-0.91) significantly reduced the incidence of SSI compared with control. Further, vancomycin soaking of the graft (86.7%) ranked first, followed by gentamicin ointment (81.1%), gentamicin irrigation (79.9%), mupirocin ointment (56.8%), triple antibiotic ointment (47.8%), gentamicin soaking of the graft (42.3%), and vancomycin powder (22.1%); ampicillin powder (17.8%) was the least effective drug. CONCLUSIONS: The findings indicate that local antibiotics combined with conventional antibiotics in the wound before wound closure are effective in reducing the incidence of SSI in clean surgical wounds. Vancomycin inoculation of the graft exhibited the best effect.

Effectiveness and safety of REBACIN as a non-invasive intervention for persistent high-risk human papillomavirus infection: A real-world prospective multicenter cohort study.

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.

Idiopathic non-cirrhotic portal hypertension in a patient with Talaromyces marneffei infection: a case report.

BACKGROUND: The etiopathogenesis of idiopathic non-cirrhotic portal hypertension (INCPH) is so far poorly understood. Altered immunity, blood diseases, infections, congenital defects and drug exposure have been documented in a part of patients with INCPH owing to increased recognition of the disorder in patients with HIV, or various haematological disorders or autoimmune diseases. We aim to discuss the possible etiopathogenesis of INCPH. CASE PRESENTATION: We reported that a patient with intestinal infection of T. Marneffei and hyper-IgE syndrome, a group of rare primary immunodeficiency disorders, was finally diagnosed with INCPH for gastroesophageal variceal bleeding. The diagnosis was mainly based on histopathological features. Transjugular intrahepatic portosystemic shunt was performed and there was no recurrence of melena during the six-month follow-up. CONCLUSION: In the context of immunodeficiency, INCPH may associated with intestinal infections. Thus, screening for enterogenic infection and immunological disorders in patients with unexplained portal hypertension is necessary.

A prediction model for left ventricular thrombus persistence/recurrence: based on a prospective study and a retrospective study.

BACKGROUND: It remains unknown whether anticoagulation for persistent left ventricular (LV) thrombus should be continued indefinitely. Identifying patients with a high risk of thrombus unresolved may be helpful to determine the optimum anticoagulation duration. This study aimed to develop a prediction model to forecast thrombus persistence or recurrence in patients with LV thrombus. METHODS: We enrolled patients prospectively from 2020 to 2022 and retrospectively from 2013 to 2019 at the National Center of Cardiovascular Diseases of China. The two cohorts were then combined to derive predictive models of thrombus persistence/recurrence. The primary study comprised patients who received systemic oral anticoagulants and had imaging records available at the end of a 3-month follow-up period. The Lasso regression algorithm and the logistic regression were performed to select independent predictors. The calibration curve was generated and a nomogram risk prediction model was applied as a risk stratification tool. RESULTS: A total of 172 (64 in the prospective cohort and 108 in the retrospective cohort) patients were included, with 124 patients in a training set and 48 patients in a validation set. Six predictors were incorporated into the multivariate logistic regression prediction model. The area under the receiving operating characteristic was 0.852 in the training set and 0.631 in the validation set. Patients with protuberant thrombus and higher baseline D-dimer levels had a reduced risk of persistence/recurrence (OR 0.17, 95% CI 0.03-0.69, P = 0.025; OR 0.67, 95% CI 0.43-0.91, P = 0.030, separately), whereas thicker thrombus was linked to an increased rate of persistent thrombus (OR 1.11, 95% CI 1.05-1.20, P = 0.002). Additionally, patients with diverse diagnoses or receiving different antiplatelet treatments had different rates of LV thrombus persistence/recurrence at 3 months. CONCLUSIONS: This prediction model provides tools to forecast the occurrence of persistent/recurrent thrombus and allows the identification of characteristics associated with unresolved thrombus. To validate the model and determine the duration of anticoagulation in patients with persistent thrombus, prospective randomized trials are necessary.

An exploratory study of effectiveness and safety of rivaroxaban in patients with left ventricular thrombus (R-DISSOLVE).

Evidence on the treatment for left ventricular (LV) thrombus is limited and mainly derives from retrospective studies. The aim of R-DISSOLVE was to explore the effectiveness and safety of rivaroxaban in patients with LV thrombus. R-DISSOLVE was a prospective, interventional, single-arm study, conducted from Oct 2020 to June 2022 at Fuwai Hospital, China. Patients with a history of LV thrombus < 3 months and with systemic anticoagulation therapy < 1 month were included. The thrombus was quantitatively confirmed by contrast-enhanced echocardiography (CE) at baseline and follow-up visits. Eligible patients were assigned to rivaroxaban (20 mg once daily or 15 mg if creatinine clearance was between 30 and 49 mL/min) and its concentration was determined by detecting anti-Xa activity. The primary efficacy outcome was the rate of LV thrombus resolution at 12 weeks. The main safety outcome was the composite of ISTH major and clinically relevant non-major bleeding. A total of 64 patients with complete CE results were analyzed for efficacy outcomes. The mean LV ejection fraction was 25.4 ± 9.0%. The dose-response curve of rivaroxaban was satisfactory based on the peak and trough plasma levels and all concentrations were in the recommended treatment range according to NOAC guidelines. The incidence rate of thrombus resolution at 6 weeks was 66.1% (41/62, 95% CI 53.0-77.7%), and of thrombus resolution or reduction was 95.2% (59/62, 95% CI 86.5-99.0%). At 12 weeks, the thrombus resolution rate was 78.1% (50/64, 95% CI 66.0-87.5%) while the rate of thrombus resolution or reduction was 95.3% (61/64, 95% CI 86.9-99.0%). The main safety outcome occurred in 4 of 75 patients (5.3%) (2 ISTH major bleeding and 2 clinically relevant non-major bleeding). In patients with LV thrombus, we reported a high thrombus resolution rate with acceptable safety by rivaroxaban, which could be a potential option for further LV thrombus treatment.Trial registration This study was registered at ClinicalTrials.gov as NCT04970381.

Preoperative prediction of the lymphovascular tumor thrombus of colorectal cancer with the iodine concentrations from dual-energy spectral CT.

BACKGROUND: The aim of this study was to explore application value of iodine concentration from dual-energy spectral computed tomography (DESCT) in preoperative prediction of lymphovascular tumor thrombus in patients with colorectal cancer (CRC). METHODS: We finally retrospectively analyzed 50 patients with CRC who underwent abdominal DESCT before receiving any preoperative treatment and underwent surgery to obtain pathological specimens which were stained with hematoxylin-eosin (HE) staining. According to the presence of cancer cell nests in blood vessels and lymphatic vessels, the subjects were divided into the positive group and negative group of lymphovascular tumor thrombus. Two radiologists independently measured the normalized iodine concentration (NIC) values, effective atomic number (Zeff) and CT values of virtual monochromatic images (VMIs) at 40-90 keV of the primary tumors in the arterial phase (AP) and venous phase (VP). Used SPSS 17.0 to calculate the receiver operating characteristic (ROC) curve to evaluate diagnostic value. RESULTS: The patients were divided into lymphovascular tumor thrombus positive group(n = 16) and negative group(n = 34). The values of NIC-AP and NIC-VP in the positive group were 0.17 ± 0.09, 0.51 ± 0.13, respectively. And those in the negative group were 0.15 ± 0.06, 0.43 ± 0.12, respectively. There was significant difference in NIC-VP value between the two groups (p = 0.039), but there was no significant difference in NIC-AP value (p = 0.423). The optimal threshold value of NIC-VP value for diagnosis of lymphovascular tumor thrombus was 0.364. The sensitivity was 68.8% and the specificity was 67.6%. CONCLUSIONS: The NIC-VP value of DESCT can be used to predict the presence or absence of the lymphovascular tumor thrombus in CRC patients before operation, which is helpful to select the best treatment scheme and evaluate its prognosis.

Utility of Contrast Echocardiography in the Diagnosis of a Primary Nonfunctioning Cardiac Paraganglioma with a Coronary Aneurysm.

Cardiac paragangliomas (PGLs) are rare neuroendocrine tumors, and data regarding the features of nonfunctioning PGLs are limited. These tumors are extensively vascularized and have high risk of hemorrhage for surgery and even biopsy. Differential diagnosis including biochemical analysis of these PGLs is important for further management. In this case report, we present the clinical, laboratory, imaging, and radionuclide presentations of a rare primary nonfunctioning cardiac PGL with a coronary aneurysm. Echocardiography initially showed a large echogenic mass in the left atrioventricular groove. The mass presented a diffuse hyperenhancement pattern with a central perfusion defect on contrast echocardiography. The tumor enclosed the left coronary artery from the coronary orifice, and an aneurysm was found in the left circumflex artery, with significantly increased flow velocity. These echocardiographic features and its susceptible location are indicative of the presence of a cardiac PGL. Although all biochemical evaluations of catecholamines from blood and urine samples were negative, positron emission tomography and scintigraphy finally confirmed the diagnosis of a primary cardiac PGL. Therefore, when imaging features are indicative of the presence of PGLs, the implementation of radionuclide imaging for final diagnosis is required even if the biochemical results are negative. Recognizing these uncommon Doppler and contrast echocardiographic characteristics is important for early diagnosing these nonfunctioning PGLs.

Guanxinning tablets improve myocardial hypertrophy by inhibiting the activation of MEK-ERK1/2 signaling pathway.

Myocardial hypertrophy may lead to heart failure and sudden death. As traditional Chinese medicine, Guanxinning tablets (GXN) have significant pharmacological effects in the prevention and treatment of cardiovascular diseases. However, the anti-cardiac hypertrophy efficacy of GXN and its mechanism of action are still unclear. Therefore, we established a heart failure rat model and isolated primary cardiomyocytes of neonatal rat to observe the protective effect of GXN on heart failure rat model and the intervention effect on myocardial cell hypertrophy, and to explore the possible mechanism of GXN preventing and treating myocardial hypertrophy. The results of in vivo experiments showed that GXN could significantly reduce the degree of cardiac hypertrophy, reduce the size of cardiomyocytes, inhibit the degree of myocardial remodeling and fibrosis, and improve cardiac function in rats with early heart failure. The results of in vitro experiments showed that GXN was safe for primary cardiomyocytes and could improve cardiomyocyte hypertrophy and reduce the apoptosis of cardiomyocytes in pathological state, which may be related to the inhibition of the over-activation of MEK-ERK1/2 signaling pathway. In conclusion, GXN may inhibit cardiac hypertrophy and improve early heart failure by inhibiting the over-activation of MEK-ERK1/2 signaling pathway.

RBM3 is an outstanding cold shock protein with multiple physiological functions beyond hypothermia.

RNA-binding motif protein 3 (RBM3), an outstanding cold shock protein, is rapidly upregulated to ensure homeostasis and survival in a cold environment, which is an important physiological mechanism in response to cold stress. Meanwhile, RBM3 has multiple physiological functions and participates in the regulation of various cellular physiological processes, such as antiapoptosis, circadian rhythm, cell cycle, reproduction, and tumogenesis. The structure, conservation, and tissue distribution of RBM3 in human are demonstrated in this review. Herein, the multiple physiological functions of RBM3 were summarized based on recent research advances. Meanwhile, the cytoprotective mechanism of RBM3 during stress under various adverse conditions and its regulation of transcription were discussed. In addition, the neuroprotection of RBM3 and its oncogenic role and controversy in various cancers were investigated in our review.

Ultra-wide transmission band frequency-selective rasorber using 2.5-D miniaturized structures.

In this paper, a miniaturized frequency-selective rasorber (FSR) with an ultra-wide transmission band (| S21 | <1 dB) is presented. The FSR is made up of a lossless multi-layer cascaded frequency-selective surface (FSS) with a 2.5-D lossy layer above, separated by an air gap. Modified metallic Jerusalem crosses loaded with lumped resistors serve as the unit cell of the lossy layer. An equivalent parallel LC circuit with high inductance and extremely low parasitic capacitance is introduced by zigzag strips and vias, which broaden the transmission band significantly. The equivalent circuit model (ECM) is constructed to provide further insight into the structure. Simulation results show that the proposed FSR exhibits an ultra-wide transmission band of 1-dB from 6.20 to 17.97 GHz (97.4%) with a minimum insertion loss of 0.074 dB. Meanwhile, an 80% absorption band covering 2.58-4.13 GHz is achieved below the passband. For demonstration, an experimental prototype of the 2.5-D FSR is fabricated and measured, and the simulated and measured results are reasonably consistent.

20 watt-level single transverse mode narrow linewidth and tunable random fiber laser at 1.5 µm band.

High power 1.5 µm band fiber lasers are of great importance for many practical applications. Generally, the technical targets including high average output power, narrow linewidth, temporally suppressed intensity dynamics, high spectral purity, single transverse mode lasing, and excellent robustness are the major concerns when constructing a high-performance laser source. Here, we demonstrate the highest output power of a wavelength tunable 1.5 µm band random fiber laser based on the active fiber gain mechanism to the best of our knowledge. A master oscillator power-amplifier (MOPA) configuration is employed to greatly boost the output power to 20 watt-level with a single transverse mode lasing and the same linewidth as the seed, benefiting from the spectral broadening free feature when employing the random fiber laser as the seed. This work not only enriches the progress of random fiber laser, but also provides an attractive alternative in realizing high performance lasing light source at 1.5 µm band.

Genome-wide association study of SARS-CoV-2 infection in Chinese population.

Coronavirus disease 2019 (COVID-19) is a global public health concern. The purpose of this study was to investigate the association between genetic variants and SARS-CoV-2 infection and the COVID-19 severity in Chinese population. A total of 256 individuals including 87 symptomatic patients (tested positive for SARS-CoV-2), 84 asymptomatic cases, and 85 close contacts of confirmed patients (tested negative for SARS-CoV-2) were recruited from February 2020 to May 2020. We carried out the whole exome genome sequencing between the individuals and conducted a genetic association study for SARS-CoV-2 infection and the COVID-19 severity. In total, we analyzed more than 100,000 single-nucleotide polymorphisms. The genome-wide association study suggested potential correlation between genetic variability in POLR2A, ANKRD27, MAN1A2, and ERAP1 genes and SARS-CoV-2 infection susceptibility. The most significant gene locus associated with SARS-CoV-2 infection was located in POLR2A (p = 5.71 × 10-6). Furthermore, genetic variants in PCNX2, CD200R1L, ZMAT3, PLCL2, NEIL3, and LINC00700 genes (p < 1 × 10-5) were closely associated with the COVID-19 severity in Chinese population. Our study confirmed that new genetic variant loci had significant association with SARS-CoV-2 infection and the COVID-19 severity in Chinese population, which provided new clues for the studies on the susceptibility of SARS-CoV-2 infection and the COVID-19 severity. These findings may give a better understanding on the molecular pathogenesis of COVID-19 and genetic basis of heterogeneous susceptibility, with potential impact on new therapeutic options.

Different Oral Antithrombotic Therapy for the Treatment of Ventricular Thrombus: An Observational Study from 2010 to 2019.

Methods: This retrospective observational study was conducted from 2010 to 2019 in National Center of Cardiovascular Diseases of China. We included patients with VT confirmed by imaging. The primary outcome was the rate of thrombus resolution. Hazard ratio (HR) was calculated with or without adjustment for covariates using Cox proportional hazards regression models. Results: 463 patients were included. 43.0% received VKAs, 16.6% received NOACs, and 40.4% received APT. Over a median of 468 days' follow-up, NOACs group was more likely to have the thrombus resolved within 12 months' follow-up than VKAs (HR 2.28, 95% CI 1.57 to 3.31) or APT (HR 2.92, 95% CI 1.97 to 4.33). After adjustment for baseline variables, the significance remained in the comparison of NOACs versus VKAs (HR 2.13, 95% CI 1.41 to 3.22) as well as NOACs versus APT (HR 2.55, 95% CI 1.53 to 4.27). No significant differences were identified in bleeding rate, thromboembolism rate, or all-cause death in 12 months' follow-up. Conclusion: Our findings showed that patients who were male, diagnosed with MI with or without ventricular aneurysm, or diagnosed with coronary artery diseases medical history had a risk of thrombus unresolved. Patients with NOACs had a higher resolution and a similar safety profile comparing VKAs or APT, which persisted after adjusting for other factors. Large randomized controlled trials are required urgently. This trial is registered with NCT05006677.

Bioprosthetic mitral valve stenosis secondary to hypereosinophilic syndrome.

Herein we present a case of hypereosinophilic syndrome (HES) with recurrent involvement of mitral valve. The patient developed mitral regurgitation secondary to HES. Surgical mitral valve replacement was performed successfully. The prosthetic valve dysfunction occurred 3 years later and echocardiography showed severe mitral valve stenosis. Extensive mural thrombi were discovered on both sides of the stenotic valve with eosinophilic infiltration. The patient underwent a repeated mechanical prosthesis replacement and recovered uneventfully.

Prognostic evaluation and immune infiltration analysis of five bioinformatic selected genes in hepatocellular carcinoma.

Despite the development in hepatocellular carcinoma (HCC) treatment in recent years, the therapeutic outcome of HCC remains unfavourable. This study examines the prognosis of HCC from a genetic level using clinical databases and single-cell data to identify genes with a high prognostic value. Three up-regulated genes (UBE2S, PTTG1, and CDC20) and two down-regulated genes (SOCS2 and DNASE1L3) in HCC tissues were identified. Various analyses confirmed its correlation with tumour stage (p < 0.01) and patient survival time (log-rank p < 0.001). Immune analysis, single-cell analysis, and gene set enrichment analysis (GSEA) were employed to provide insight on how they affect cancer progression, and we observed a close relation between these genes and tumour immune infiltration. Eventually, we constructed a risk score system that risk score = (0.0465) × UBE2S + (0.1851) × CDC20 + (-0.0461) × DNASE1L3 + (-0.2279) × SOCS2 (5-year area under curve = 0.706). The risk score system may serve as an effective novel prognostic system for HCC patients. This study might provide novel ideas for prognostic or therapeutic biomarkers for HCC.

Longitudinal Dynamics of the Neutralizing Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic with no licensed vaccine or specific antiviral agents for therapy. Little is known about the longitudinal dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific neutralizing antibodies (NAbs) in patients with COVID-19. METHODS: Blood samples (n = 173) were collected from 30 patients with COVID-19 over a 3-month period after symptom onset and analyzed for SARS-CoV-2-specific NAbs using the lentiviral pseudotype assay, coincident with the levels of IgG and proinflammatory cytokines. RESULTS: SARS-CoV-2-specific NAb titers were low for the first 7-10 days after symptom onset and increased after 2-3 weeks. The median peak time for NAbs was 33 days (interquartile range [IQR], 24-59 days) after symptom onset. NAb titers in 93.3% (28/30) of the patients declined gradually over the 3-month study period, with a median decrease of 34.8% (IQR, 19.6-42.4%). NAb titers increased over time in parallel with the rise in immunoglobulin G (IgG) antibody levels, correlating well at week 3 (r = 0.41, P < .05). The NAb titers also demonstrated a significant positive correlation with levels of plasma proinflammatory cytokines, including stem cell factor (SCF), TNF-related apoptosis-inducing ligand (TRAIL), and macrophage colony-stimulating factor (M-CSF). CONCLUSIONS: These data provide useful information regarding dynamic changes in NAbs in patients with COVID-19 during the acute and convalescent phases.

Dicoumarol, an NQO1 inhibitor, blocks cccDNA transcription by promoting degradation of HBx.

BACKGROUND & AIMS: Current antiviral therapies help keep HBV under control, but they are not curative, as they are unable to eliminate the intracellular viral replication intermediate termed covalently closed circular DNA (cccDNA). Therefore, there remains an urgent need to develop strategies to cure CHB. Functional silencing of cccDNA is a crucial curative strategy that may be achieved by targeting the viral protein HBx. METHODS: We screened 2,000 small-molecule compounds for their ability to inhibit HiBiT-tagged HBx (HiBiT-HBx) expression by using a HiBiT lytic detection system. The antiviral activity of a candidate compound and underlying mechanism of its effect on cccDNA transcription were evaluated in HBV-infected cells and a humanised liver mouse model. RESULTS: Dicoumarol, an inhibitor of NAD(P)H:quinone oxidoreductase 1 (NQO1), significantly reduced HBx expression. Moreover, dicoumarol showed potent antiviral activity against HBV RNAs, HBV DNA, HBsAg and HBc protein in HBV-infected cells and a humanised liver mouse model. Mechanistic studies demonstrated that endogenous NQO1 binds to and protects HBx protein from 20S proteasome-mediated degradation. NQO1 knockdown or dicoumarol treatment significantly reduced the recruitment of HBx to cccDNA and inhibited the transcriptional activity of cccDNA, which was associated with the establishment of a repressive chromatin state. The absence of HBx markedly blocked the antiviral effect induced by NQO1 knockdown or dicoumarol treatment in HBV-infected cells. CONCLUSIONS: Herein, we report on a novel small molecule that targets HBx to combat chronic HBV infection; we also reveal that NQO1 has a role in HBV replication through the regulation of HBx protein stability. LAY SUMMARY: Current antiviral therapies for hepatitis B are not curative because of their inability to eliminate covalently closed circular DNA (cccDNA), which persists in the nuclei of infected cells. HBV X (HBx) protein has an important role in regulating cccDNA transcription. Thus, targeting HBx to silence cccDNA transcription could be an important curative strategy. We identified that the small molecule dicoumarol could block cccDNA transcription by promoting HBx degradation; this is a promising therapeutic strategy for the treatment of chronic hepatitis B.