Epstein-Barr virus variation in people living with human immunodeficiency virus in southeastern China.

BACKGROUND: Patients infected with HIV are at high risk of developing Epstein-Barr Virus (EBV)-related diseases. The genotype and viral biological behavior of EBV infection in patients with human immunodeficiency virus-1 (HIV) in China remain unclear. This study analyzed the characteristics of EBV in patients infected with HIV in southeastern China. METHODS: A total of 162 HIV-infected patients and 52 patients without HIV were enrolled in this study. EBV viral load in blood was determined by fluorescence quantitative PCR. EBV typing was performed using saliva according to polymorphisms in the EBNA3C region. EBV LMP-1 carboxy terminus (C-ter) was sequenced, and compared with the epidemic strains in the world. RESULTS: Among HIV infected patients, the EBV strain variant was mainly EBV-1, while EBV-2 had a higher viral load than EBV-1 (P = 0.001) and EBV-1/2 (P = 0.002). HIV infected patients had higher active virus replication. The EBV LMP-1 variants were mainly the China1 variant. HIV-infected patients had different nucleic acid positions of 30-bp deletion (del30) and had a higher incidence of high 33-bp tandem repeats (rep33) copies than non-HIV-infected patients. There was a difference in the mutations of EBV LMP-1 C-ter del30 and ins15 between HIV infected patients and the control group (P < 0.001). CONCLUSION: In southeastern China, EBV in HIV-infected patients had higher active virus replication; EBV infection was mainly EBV-1, and EBV-2 infection has higher EBV virus load; hotspot mutations of LMP-1 C-ter were different between HIV-infected patients and non-HIV-infected patients. TRIAL REGISTRATION: This study was approved by the ethics committee of the First Affiliated Hospital of Zhejiang University School of Medicine (Approval No. 2018764), and registered in Chinese Clinical Trial Registry on 3 June 2019 (ChiCTR, ChiCTR1900023600, http://www.chictr.org.cn/usercenter.aspx ).

Survival Outcomes and Safety of Programmed Cell Death/Programmed Cell Death Ligand 1 Inhibitors for Unresectable Hepatocellular Carcinoma: Result From Phase III Trials.

Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. The aim of this study was conducted a meta-analysis to assess the efficacy and safety of PD-1/PD-L1 inhibitors in patients with unresectable hepatocellular carcinoma (uHCC). A total of 1657 patients were included. The completed phase III trials with details data, such as overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse effects (AEs) were included. The pooled hazard ratio (HR) of OS and PFS were .75 (95% CI: .61-.92) and .74 (95% CI: .56-.97) with heterogeneity between PD-1/PD-L1 inhibitors groups and control groups. Sensitivity analysis revealed IMbrave-150 could be the most important factor of heterogeneity for OS, while CheckMate-459 was the main fact of heterogeneity for PFS. In addition, the relative risk (RR) of ORR and DCR were 2.43 (95% CI: 1.80-3.26) and 1.26 (95% CI: 1.11-1.43) with low heterogeneity in PD-1/PD-L1 inhibitors groups. The therapeutic effect of PD-1/PD-L1 inhibitors was better in females, Asia without Japan, BCLC status C and infected hepatitis groups. The RR of AEs from any cause and serious adverse events (SAEs) for patients receiving PD-1/PD-L1 inhibitors were 1.03 (95% CI: .93-1.13) and 1.13 (95% CI: .89-1.44), respectively. Pruritus was the most common AEs reported in 10% of patients or more (RR = 1.69, 95% CI: 1.33-2.15). In conclusion, PD-L1 inhibitor combined with anti-VEGF antibody could improve the prognosis of patients with uHCC. However, caution should be taken for AEs during patients receiving PD-1/PD-L1 inhibitors.

One-year follow-up of chest CT findings in patients after SARS-CoV-2 infection.

BACKGROUND: Knowledge about the 1-year outcome of COVID-19 is limited. The aim of this study was to follow-up and evaluate lung abnormalities on serial computed tomography (CT) scans in patients with COVID-19 after hospital discharge. METHODS: A prospective cohort study of patients with COVID-19 from the First Affiliated Hospital, Zhejiang University School of Medicine was conducted, with assessments of chest CT during hospitalization and at 2 weeks, 1 month, 3 months, 6 months, and 1 year after hospital discharge. Risk factors of residual CT opacities and the influence of residual CT abnormalities on pulmonary functions at 1 year were also evaluated. RESULTS: A total of 41 patients were followed in this study. Gradual recovery after hospital discharge was confirmed by the serial CT scores. Around 47% of the patients showed residual aberration on pulmonary CT with a median CT score of 0 (interquartile range (IQR) of 0-2) at 1 year after discharge, with ground-glass opacity (GGO) with reticular pattern as the major radiologic pattern. Patients with residual radiological abnormalities were older (p = 0.01), with higher rate in current smokers (p = 0.04), higher rate in hypertensives (p = 0.05), lower SaO2 (p = 0.004), and higher prevalence of secondary bacterial infections during acute phase (p = 0.02). Multiple logistic regression analyses indicated that age was a risk factor associated with residual radiological abnormalities (OR 1.08, 95% CI 1.01-1.15, p = 0.02). Pulmonary functions of total lung capacity (p = 0.008) and residual volume (p < 0.001) were reduced in patients with residual CT abnormalities and were negatively correlated with CT scores. CONCLUSION: During 1-year follow-up after discharge, COVID-19 survivors showed continuous improvement on chest CT. However, residual lesions could still be observed and correlated with lung volume parameters. The risk of developing residual CT opacities increases with age.

Clinical efficacy of methylprednisolone and the combined use of lopinavir/ritonavir with arbidol in treatment of coronavirus disease 2019.

This study aims to comparatively analyze the therapeutic efficacy upon multiple medication plans over lopinavir/ritonavir (LPV/r), arbidol (ARB), and methylprednisolone on patients with coronavirus disease 2019 (COVID-19). Totally, 75 COVID-19 patients admitted to The First Affiliated Hospital, Zhejiang University School of Medicine from January 22, 2020 to February 29, 2020 were recruited and grouped based on whether or not LPV/r and ARB were jointly used and whether or not methylprednisolone was used. Indexes including body temperature, time for nucleic acid negative conversion, hospital stays, and laboratory indexes were examined and compared. For all patients, there were no significant differences in the change of body temperature, the time for negative conversion, and hospital stays whether LPV/r and ARB were jointly used or not. While for severe and critically severe patients, methylprednisolone noticeably reduced the time for negative conversion. Meanwhile, the clinical efficacy was superior on patients receiving methylprednisolone within 3 days upon admission, and the duration of hospital stays was much shorter when methylprednisolone was given at a total dose of 0-400 mg than a higher dose of >400 mg if all patients received a similar dose per day. Nonetheless, no significant changes across hepatic, renal, and myocardial function indexes were observed. LPV/r combined with ARB produced no noticeably better effect on COVID-19 patients relative to the single-agent treatment. Additionally, methylprednisolone was efficient in severe and critically severe cases, and superior efficacy could be realized upon its early, appropriate, and short-term application.

Switch to Efavirenz Attenuates Lipoatrophy in Girls With Perinatal HIV.

OBJECTIVES: Children with HIV (CHIV) have lifetime exposure to antiretrovirals (ART); therefore, optimizing their regimens to have the least impact on fat redistribution is a priority. METHODS: This is a cross-sectional study of 219 perinatally infected CHIV and 219 HIV-uninfected controls from similar socioeconomic backgrounds in Johannesburg, South Africa. We compared total body and regional fat distribution in CHIV on suppressive ART regimens with controls and, among CHIV, between ritonavir-boosted lopinavir (LPV/r)-based and efavirenz (EFV)-based regimens. RESULTS: The mean age of the 219 uninfected children (45% girls) and the 219 CHIV (48% girls) was 7.0 and 6.4 years, respectively. CHIV had lower adjusted total body fat (P = 0.005) and lower percentage fat at the trunk (P = 0.020), arms (P = 0.001), and legs (P < 0.001) than uninfected children. CHIV on LPV/r had similar body composition as those on EFV, except for arm fat mass (P = 0.030). When stratified by sex, girls with HIV on LPV/r had lower adjusted total (P = 0.007), trunk (P = 0.002), arms (P = 0.008), legs (P = 0.048) fat mass; trunk-to-total body fat (P = 0.044); and higher legs-to-total body fat (P = 0.011) than those on EFV. CONCLUSIONS: South African CHIV receiving ART had lower global and partial fat mass and percentage fat than healthy controls. In girls with HIV with sustained virologic suppression on ART, switching from LPV/r to EFV could attenuate fat mass loss, indicating that EFV-based regimen may be a better option in this group of individuals.

Predictors of COVID-19 Infection: A Prevalence Study of Hospitalized Patients.

AIM: To find the predictors of coronavirus disease 2019 (COVID-19) in hospitalized patients. METHODS: A prevalence study compared the characteristics of COVID-19 patients with non-COVID-19 patients from January 19, 2020, to February 18, 2020, during the COVID-19 outbreak. Laboratory test results and pulmonary chest imaging of confirmed COVID-19 and non-COVID-19 patients were collected by retrieving medical records in our center. RESULTS: 96 COVID-19 patients and 122 non-COVID-19 patients were enrolled in this study. COVID-19 patients were older (53 vs. 39; P < 0.001) and had higher body mass index (BMI) than non-COVID-19 group (24.21 ± 3.51 vs. 23.00 ± 3.27, P = 0.011); however, differences in gender were not observed between the two groups. Logistic regression analysis showed that exposure history (OR: 23.34, P < 0.001), rhinorrhea (odds radio (OR): 0.12, P = 0.006), alanine aminotransferase (ALT) (OR: 1.03, P = 0.049), lactate dehydrogenase (LDH) (OR: 1.01, P = 0.020), lymphocyte (OR: 0.27, P = 0.007), and bilateral involvement on chest CT imaging (OR: 23.01, P < 0.001) were independent risk factors for COVID-19. Moreover, bilateral involvement on chest CT imaging (AUC = 0.904, P < 0.001) had significantly higher AUC than others in predicting COVID-19. CONCLUSIONS: Exposure history, elevated ALT and LDH, absence of rhinorrhea, lymphopenia, and bilateral involvement on chest CT imaging provide robust evidence for the diagnosis of COVID-19, especially in resource-limited conditions where nucleic acid detection is not readily available.

Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms.

OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.

Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19).

BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. METHODS: In this retrospective study, risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from 2 hospitals outside Wuhan. RESULTS: The median (interquartile range) duration of SARS-CoV-2 RNA detection was 17 (13-22) days as measured from illness onset. When comparing patients with early (<15 days) and late (≥15 days after illness onset) viral RNA clearance, prolonged SARS-CoV-2 RNA shedding was associated with male sex (P = .009), old age (P = .033), concomitant hypertension (P = .009), delayed admission to hospital after illness onset (P = .001), severe illness at admission (P = .049), invasive mechanical ventilation (P = .006), and corticosteroid treatment (P = .025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (P < .001) and focal absorption on radiograph images (P < .001) than patients with early SARS-CoV-2 RNA clearance. Male sex (OR, 3.24; 95% CI, 1.31-8.02), delayed hospital admission (OR, 1.30; 95% CI, 1.10-1.54), and invasive mechanical ventilation (OR, 9.88; 95% CI, 1.11-88.02) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. CONCLUSIONS: Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.

Activation of the kynurenine pathway is associated with poor outcome in Pneumocystis pneumonia patients infected with HIV: results of 2 months cohort study.

BACKGROUND: Indoleamine 2, 3-dioxygenase (IDO) is a key enzyme in the degradation of tryptophan (Trp) to kynurenine (Kyn). We measured IDO activity as the Kyn to Trp ratio, and investigated whether IDO could be used to assess prognosis of acquired immune deficiency Sydrome (AIDS) patients with pneumocystis pneumonia (PCP). METHODS: The Kyn and Trp concentration were measured by UPLC-MS/MS in plasma samples. A total of 49 AIDS-PCP patients were included in the analysis. Clinical characteristics and Kyn/Trp ratio were compared between survivors and non-survivors. RESULTS: Kyn/Trp ratio was significantly lower after anti-PCP treatment in AIDS patients with PCP (P < 0.0001). Plasma Kyn/Trp ratio was higher in patients with PaO2/FiO2 ≤ 300 mmHg than in those with PaO2/FiO2 > 300 mmHg (P = 0.007). Kyn/Trp ratio, D-dimer and CRP showed much higher AUC for predicting death of AIDS-PCP patients. Kyn/Trp ratio was useful for predicting the mortality of AIDS-PCP due to a significantly higher Kyn/Trp ratio in the non-survivors (P = 0.002). And the high Kyn/Trp ratio group had higher mortality rate than low Kyn/Trp group (32.1% vs. 9.1%, respectively, p = 0.024). CONCLUSION: Activation of the kynurenine pathway is associated with the severity and fatal outcomes of AIDS patients with pneumocystis pneumonia.

Detection of Liquid Penetration of a Micropillar Surface Using the Quartz Crystal Microbalance.

A quantitative characterization of the wetting states of droplets on hydrophobic textured surfaces requires direct measurement of the liquid penetration into surface cavities, which is challenging. Here, the use of quartz crystal microbalance (QCM) technology is reported for the characterization of the liquid penetration depth on a micropillar-patterned surface. The actual liquid-air interface of the droplet was established by freezing the droplet and characterizing it using a cryogenically focused ion beam/scanning electron microscope (cryo FIB-SEM) technique. It was found that a direct correlation exists between the liquid penetration depth and the responses of the QCM. A very small frequency shift of the QCM (1.5%) was recorded when the droplet was in the Cassie state, whereas a significant frequency shift was observed when the wetting state changed to the Wenzel state (where full liquid penetration occurs). Furthermore, a transition from the Cassie to the Wenzel state can be captured by the QCM technique. An acoustic-structure-interaction based numerical model was developed to further understand the effect of penetration. The numerical model was validated by experimentally measured responses of micropillar-patterned QCMs. The results also show a nonlinear response of the QCM to the increasing liquid penetration depth. This research provides a solid foundation for utilizing QCM sensors for liquid penetration and surface wettability characterization.

Nuclear Factor of Activated T Cells and Cytokines Gene Expression of the T Cells in AIDS Patients with Immune Reconstitution Inflammatory Syndrome during Highly Active Antiretroviral Therapy.

Background. The etiology of immune reconstitution inflammatory syndrome (IRIS) in AIDS patients after the initiation of HAART remains unknown. Several researches indicated that the development of IRIS is associated with the production and variation of cytokines, whose gene expression are closely related to the Ca2+/CN-nuclear factor of activated T cells (NFAT) pathway. Methods. We studied the expression of NFAT isoforms and their major target cytokines genes in peripheral blood CD3+ T cells of subjects through fluorescence quantitative PCR and explored the expression changes of these genes before and after HAART. Results. After the initiation of HARRT, NFAT1, IL-6, and IL-8 gene expression showed a reversal trend in the CD3+ T cells of the IRIS group and changed from low expression before HARRT to high expression after HARRT. In particular, the relative gene expression of NFAT1 was markedly higher compared with the other three isoforms. The IRIS group also showed higher NFAT4, NFAT2, NFAT1, IL-1ß, IL-10, IL-2, IL-18, and TNF-α gene expression than the non-IRIS group. Conclusion. This study suggested that high expression levels of IL-2, IL-6, IL-8, TNF-α, IL-1ß, IL-10, IL-12, and IL-18 can predict the risk of IRIS. The increased expression of NFAT1 and NFAT4 may promote the expression of cytokines, such as IL-6, IL-8, and TNF-α, which may promote the occurrence of IRIS.

Role of nanoparticles in wavelength selectivity of multilayered structures in the far-field and near-field regimes.

Microscopic thin films have shown wavelength selectivity in the context of radiative heat transfer. We propose a methodology to shift the wavelength selectivity in the desired location. This work deals with the far-field and near-field radiation from thin films embedded with nanoparticles. The calculations of emission spectra are performed using the Fresnel equations in the far-field limit, and using the dyadic Green's function formalism for transmissivity between the closely spaced objects in the near-field regime. For the media doped with nanoparticles, an effective dielectric function using the Maxwell-Garnett-Mie theory is used to calculate emissivity and radiative heat transfer. It has been shown that the wavelength selectivity in the emission spectra can be influenced by varying the size and/or the volume fraction of nanoparticles. We characterize the wavelength selectivity using real and imaginary parts of the effective refractive index. We show that the influence of nanoparticles on wavelength selectivity is different depending on whether the particles are of polar materials or are metallic.

Prenatal diagnosis and molecular cytogenetic characterization of a de novo pure distal 9p deletion and literature review.

We present rapid aneuploidy diagnosis of distal 9p deletion by array comparative genomic hybridization using uncultured amniocytes in a pregnancy associated with an abnormal maternal serum screening result and intrauterine growth restriction (IUGR) in the fetus. We review the literature of prenatal diagnosis of distal 9p deletion, and add abnormal maternal serum biochemistry and fetal IUGR in the distinctive prenatal findings in pregnancy with fetal distal 9p deletion. We discuss the consequence of haploinsufficiency of DOCK8, KANK1, VLDLR and DMRT1 in this case.

Identification of an IGHV3-53-Encoded RBD-Targeting Cross-Neutralizing Antibody from an Early COVID-19 Convalescent.

Since November 2021, Omicron has emerged as the dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, and its sublineages continue to appear one after another, significantly reducing the effectiveness of existing therapeutic neutralizing antibodies (NAbs). It is urgent to develop effective NAbs against circulating Omicron variants. Here, we isolated receptor binding domain (RBD)-specific single memory B cells via flow cytometry from a COVID-19 convalescent. The antibody variable region genes of the heavy chain (VHs) and light chain (VLs) were amplified and cloned into expression vectors. After antibody expression, ELISA screening and neutralizing activity detection, we obtained an IGHV3-53-encoded RBD-targeting cross-neutralizing antibody D6, whose VL originated from the IGKV1-9*01 germlines. D6 could potently neutralize circulating Omicron variants (BA.1, BA.2, BA.4/5 and BF.7), with IC50 values of less than 0.04 µg/mL, and the neutralizing ability against XBB was reduced but still effective. The KD values of D6 binding with RBD of the prototype and BA.1 were both less than 1.0 × 10-12 M. The protein structure of the D6-RBD model indicates that D6 interacts with the RBD external subdomain and belongs to the RBD-1 community. The sufficient contact and deep interaction of D6 HCDR3 and LCDR3 with RBD may be the crucial reason for its cross-neutralizing activity. The sorting and analysis of mAb D6 will provide important information for the development of anti-COVID-19 reagents.

Molecular features and clinical outcomes of EGFR-mutated, MET-amplified non-small-cell lung cancer after resistance to dual-targeted therapy.

Background: Some studies of dual-targeted therapy (DTT) targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) have shown promising efficacy in non-small-cell lung cancer (NSCLC). Consequently, patient management following DTT resistance has gained significance. However, the underlying resistance mechanisms and clinical outcomes in these patients remain unclear. Objectives: This study aimed to delineate the molecular characteristics and survival outcomes of patients with NSCLC harboring EGFR mutations and acquired MET amplification after developing resistance to DTT. Design: We conducted a retrospective analysis of patients with NSCLC with EGFR mutations and acquired MET amplification who exhibited resistance to EGFR/MET DTT. Methods: Next-generation sequencing (NGS) was performed on patients with available tissue samples before and/or after the development of resistance to DTT. Stratified analyses were carried out based on data sources and subsequent salvage treatments. Univariate/multivariate Cox regression models and survival analyses were employed to explore potential independent prognostic factors. Results: The study included 77 NSCLC patients, with NGS conducted on 19 patients. We observed many resistance mechanisms, including EGFR-dependent pathways (4/19, 21.1%), MET-dependent pathways (2/19, 10.5%), EGFR/MET co-dependent pathways (2/19, 10.5%), and EGFR/MET-independent resistance mechanisms (11/19, 57.9%). Post-progression progression-free survival (pPFS) and post-progression overall survival (pOS) significantly varied among patients who received the best supportive care (BSC), targeted therapy, or chemotherapy (CT), with median pPFS of 1.5, 3.9, and 4.9 months, respectively (p = 0.003). Median pOS were 2.3, 7.7, and 9.2 months, respectively (p < 0.001). The number of treatment lines following DTT resistance and the Eastern Cooperative Oncology Group performance status emerged as the independent prognostic factors. Conclusion: This study revealed a heterogeneous landscape of resistance mechanisms to EGFR/MET DTT, with a similar prevalence of on- and off-target mechanisms. Targeted therapy or CT, as compared to BSC, exhibited the potential to improve survival outcomes for patients with advanced NSCLC following resistance to DTT.

Distinct Lipidomic Profiles between People Living with HIV Treated with E/C/F/TAF or B/F/TAF: An Open-Label Prospective Cohort Study.

INTRODUCTION: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) has been increasingly replaced by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in the treatment of human immunodeficiency virus (HIV) owing to its more favorable pharmacokinetics and fewer drug-drug interactions. However, the effect of this switch on plasma lipids and lipidomic profiles remains poorly characterized. METHODS: HIV infected patients on an E/C/F/TAF regimen were recruited into the study and followed up every 12 weeks. Participants were divided into E/C/F/TAF and B/F/TAF groups depending on whether they were switched to B/F/TAF during follow-up. Clinical information and blood samples were collected at 0, 12, and 24 weeks, and lipidomic analysis was performed using liquid chromatography mass spectrometry. RESULTS: No significant differences were observed between the groups at baseline. At week 24, patients switched to B/F/TAF had lower triglyceride [mmol/L; 1.23 (0.62) versus 2.03 (0.75), P = 0.001] and very low-density lipoprotein cholesterol [mmol/L; 0.64 (0.26) versus 0.84 (0.32), P = 0.037) compared with patients who continued E/C/F/TAF therapy. Small decrease from baseline in Framingham general cardiovascular risk score (FRS) was observed in the B/F/TAF arm [week (W) 0: 2.59 (1.57) versus W24: 2.18 (1.01), P = 0.043]. Lipidomic analysis indicated that E/C/F/TAF treatment increased the levels of several diglycerides (DGs), triacylglycerols (TAGs), and lyso-phosphatidylcholines (LPCs), whereas switching to B/F/TAF led to increased sphingolipids and glycerophospholipids. After adjusting for demographic and clinical parameters, only DG (16:0/18:2), DG (18:2/22:6), DG (18:3/18:2), DG (20:5/18:2), TAG (18:3/18:2/21:5), TAG (20:5/18:2/22:6), and LPC (22:6) were found to be significantly associated with FRS (regression coefficient of 0.17-6.02, P < 0.05). Most of these FRS associate lipid species were significantly elevated in individuals treated with E/C/F/TAF instead of individuals treated with B/F/TAF. CONCLUSION: E/C/F/TAF promotes the accumulation of lipid species closely associated with cardiovascular disease (CVD) risk among people living with HIV, whereas B/F/TAF has a decreased impact on CVD-related lipid profile and is associated with lower CVD risk. A graphical abstract is available with this article. TRIAL REGISTRATION: ClinicalTrials.gov; identifier, NCT06019273.

Plasma ddPCR for the detection of MET amplification in advanced NSCLC patients: a comparative real-world study.

Background: Mesenchymal-epithelial transition (MET) amplification is a crucial oncogenic driver and a resistance mechanism to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) of non-small-cell lung cancer (NSCLC). Fluorescence in situ hybridization (FISH) is the gold standard for MET amplification detection. However, it is inapplicable when tissue samples are unavailable. Objective: This study assessed the performance of plasma droplet digital polymerase chain reaction (ddPCR) in MET amplification detection in NSCLC patients. Design and methods: A total of 87 NSCLC patients were enrolled, and 94 paired tissue and plasma samples were analyzed for the concordance between FISH and plasma ddPCR/tissue next-generation sequencing (NGS) in detecting MET amplification. In addition, the efficacy of patients with MET amplification using different detection methods who were treated with MET-TKIs was evaluated. Results: Plasma ddPCR showed substantial concordance with FISH (74.1% sensitivity, 92.5% specificity, and 87.2% accuracy with a kappa value of 0.68) and outperformed tissue NGS (kappa value of 0.64) in MET amplification detection. Combined plasma ddPCR and tissue NGS showed substantial concordance with FISH (92.3% sensitivity, 89.2% specificity, and an accuracy of 90.1% with a kappa value of 0.77). The efficacy is comparable in these NSCLC patients with MET amplification detected by FISH and plasma ddPCR who were treated with MET-TKIs. Conclusion: Plasma ddPCR is a potentially reliable method for detecting MET amplification in advanced NSCLC patients. Combined plasma ddPCR and tissue NGS might be an alternative or complementary method to MET amplification detection.

Matching method between nanoparticle displacement agent size and pore throat in low permeability reservoir.

Nano-particles possess desirable attributes such as small particle size, excellent injectivity, and migration performance, making them highly compatible and adaptable for addressing the water flooding requirements of the low-permeability oil reservoir. When selecting an oil displacement agent for enhancing water flooding and improving oil recovery, factors such as injectivity and migration need to be carefully considered. In this study, through a comprehensive analysis of the mechanism and technical characteristics of nano-particle oil displacement agents, the plugging and profile control mechanisms recognized by the mainstream of nano-particles are elucidated. By examining various elements including outcrop fractures, natural micro-fractures, artificial support fractures, and dynamic monitoring data, a reevaluation of the dominant channel scale governing water drive in low permeability reservoirs is conducted, thereby defining the target entities for profile control and flooding operations. Drawing upon Darcy's percolation law and leveraging enhanced oil recovery techniques based on the classical Kozeny equation, a profile control and flooding mechanism is proposed that focuses on increasing the specific surface area of polymer particles while simultaneously reducing reservoir permeability. This innovative approach establishes a novel matching method between nano-polymer particles and the diverse media found within the reservoir. Lastly, the application of nanoparticle flooding technology in Changqing Oilfield is presented, highlighting its practical implementation and benefits.

Insights into the Microscopic Oil-Water Flow Characteristics and Displacement Mechanisms during Waterflooding in Sandstone Reservoir Rock Based on Micro-CT Technology: A Pore-Scale Numerical Simulation Study.

The low oil recovery rate observed in current oil fields is largely attributed to the presence of remaining oil trapped in the pores of porous media during waterflooding. To improve the recovery rate, it is imperative to gain an understanding of the oil-water flow characteristics and displacement mechanisms during waterflooding, as well as to elucidate the underlying mobilization mechanisms of residual oil at the pore scale. In this paper, we explore these issues in depth by numerically investigating the influence of factors such as water injection velocities, oil-water viscosity ratios, and wettability conditions on pore-scale oil-water flow characteristics and oil recovery rate. To this end, we employ a direct numerical simulation (DNS) method in conjunction with the volume of fluid (VOF) method to study the microscopic displacement mechanisms of waterflooding in a reconstructed two-dimensional digital rock core based on micro-CT technology. In addition, the particle tracing method is adopted to identify the flow path and dominant areas during waterflooding in order to mobilize the residual oil within the pores. The findings indicate that the oil-water flow characteristics in porous media are determined by the interplay between capillary and viscous forces. Furthermore, the oil recovery rate is 10.6% and 24.7% lower under strong water-wet and oil-wet conditions than that (32.36%) under intermediate wettability conditions, and the final oil recovery rate is higher under water-wet conditions than under oil-wet conditions. The seepage path and the dominant areas are directly linked to the capillarity formed during waterflooding. The findings of this study are significant in terms of enhancing the recovery rate of residual oil and provide a novel perspective for understanding the waterflooding process.

The role of pyroptosis-related genes in the diagnosis and subclassification of sepsis.

Pyroptosis is a new form of programmed cell death recognized as crucial in developing sepsis. However, there is limited research on the mechanism of pyroptosis-related genes in sepsis-related from the Gene Expression Omnibus (GEO) database and standardized. The expression levels of pyroptosis-related genes were extracted, and differential expression analysis was conducted. A prediction model was constructed using random forest (RF), support vector machine (SVM), weighted gene co-expression new analysis (WGCNA), and nomogram techniques to assess the risk of sepsis. The relationship between pyroptosis-related subgroups and the immune microenvironment and inflammatory factors was studied using consistent clustering algorithms, principal component analysis (PCA), single-sample genomic enrichment analysis (ssGSEA), and immune infiltration. A risk prediction model based on 3 PRGs has been constructed and can effectively predict the risk of sepsis. Patients with sepsis can be divided into two completely different subtypes of pyroptosis-related clusters. Cluster B is highly correlated with the lower proportion of Th17 celld and has lower levels of expression of inflammatory factors. This study utilizes mechanical learning methods to further investigate the pathogenesis of sepsis, explore potential biomarkers, provide effective molecular targets for its diagnosis and treatment of sepsis.