Rapid Initiation of Antiretroviral Therapy With Coformulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide Versus Efavirenz, Lamivudine, and Tenofovir Disoproxil Fumarate in HIV-Positive Men Who Have Sex With Men in China: Week 48 Results of the Multicenter, Randomized Clinical Trial.

BACKGROUND: Most international treatment guidelines recommend rapid initiation of antiretroviral therapy (ART) for people newly diagnosed with human immunodeficiency virus (HIV)-1 infection, but experiences with rapid ART initiation remain limited in China. We aimed to evaluate the efficacy and safety of efavirenz (400 mg) plus lamivudine and tenofovir disoproxil fumarate (EFV + 3TC + TDF) versus coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in rapid ART initiation among men who have sex with men (MSM) who have been diagnosed with HIV. METHODS: This multicenter, open-label, randomized clinical trial enrolled MSM aged ≥18 years to start ART within 14 days of confirmed HIV diagnosis. The participants were randomly assigned in a 1:1 ratio to receive EFV (400 mg) + 3TC + TDF or BIC/FTC/TAF. The primary end point was viral suppression (<50 copies/mL) at 48 weeks per US Food and Drug Administration Snapshot analysis. RESULTS: Between March 2021 and July 2022, 300 participants were enrolled; 154 were assigned to receive EFV + 3TC + TDF (EFV group) and 146 BIC/FTC/TAF (BIC group). At week 48, 118 (79.2%) and 140 (95.9%) participants in the EFV and BIC group, respectively, were retained in care with viral suppression, and 24 (16.1%) and 1 (0.7%) participant in the EFV and BIC group (P < .001), respectively, discontinued treatment because of adverse effects, death, or lost to follow-up. The median increase of CD4 count was 181 and 223 cells/µL (P = .020), respectively, for the EFV and BIC group, at week 48. The overall incidence of adverse effects was significantly higher for the EFV group (65.8% vs 37.7%, P < .001). CONCLUSIONS: BIC/FTC/TAF was more efficacious and safer than EFV (400 mg) + 3TC + TDF for rapid ART initiation among HIV-positive MSM in China.

Cancer Risk and its Association With Diabetes Mellitus in Patients With Acromegaly: A Two Center-based Study.

OBJECTIVE: To compare the incidence of cancer in patients with acromegaly with that of the local population in China and explore possible risk factors. METHODS: Data from 117 patients diagnosed with acromegaly at 2 centers between 2011 and 2022 were analyzed, and their cancer diagnoses were recorded. The cancer standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated by comparison with those of the local population. The patients were divided into 2 groups, having cancer diagnosis or not. The relationships between cancer and sex, body mass index, age, growth hormone levels, diagnosis delay, tumor size, disease duration, treatment, disease status, and other comorbidities were analyzed. RESULTS: Eight (6.8%) of 117 patients were diagnosed with cancer. The incidence of overall (SIR = 3.29, 95% CI = 1.42-6.94), colorectal (SIR = 16.67, 95% CI = 4.45-42.67), and thyroid cancers (SIR = 14.29, 95% CI = 1.73-51.60) was increased, but that of lung cancer (SIR = 4.17, 95% CI = 0.50-15.05) was not. Diagnostic delay (10.1[8.6-14.3] vs 3.8[1.3-9.0]; P = .005) and duration of acromegaly (12.8[8.9-16.4] vs 5.6[2.3-10.9]; P = .008) were prolonged in the cancer group. Diabetes mellitus (odds ratio = 7.01, 95% CI = 1.23-39.99) was an independent risk factor for acromegaly with cancer. CONCLUSION: Acromegaly patients are at a higher risk of cancer and its association with diabetes mellitus. Considering the rarity of the disease, an Acromegaly Cancer Registry Center should be established in China as soon as possible.

rhG-CSF is associated with an increased risk of metastasis in NSCLC patients following postoperative chemotherapy.

BACKGROUND: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) reduces neutropenia events and is widely used in cancer patients receiving chemotherapy. However, the effects of rhG-CSF on distant organ metastasis (DOM) in non-small-cell lung cancer (NSCLC) patients following postoperative chemotherapy are not clear. METHODS: A retrospective cohort study was performed on NSCLC patients who underwent complete surgical resection and postoperative systemic chemotherapy at The First Affiliated Hospital of Nanchang University between 1 January 2012 and 31 December 2017. The effect of rhG-CSF on DOM was assessed with other confounding factors using Cox regression analyses. RESULTS: We identified 307 NSCLC patients who received postoperative systemic chemotherapy (n = 246 in the rhG-CSF group, n = 61 in the No rhG-CSF group). The incidence of DOM in postoperative NSCLC patients with rhG-CSF treatment was observably higher than in patients without rhG-CSF treatment (48.3% vs. 27.9%, p < 0.05). Univariate regression analysis revealed that rhG-CSF and pathological stage were independent risk factors for metastasis-free survival (MFS) (p < 0.05). RhG-CSF users had a higher risk of DOM (adjusted HR: 2.33, 95% CI: 1.31-4.15) than nonusers of rhG-CSF. The association between rhG-CSF and the risk of DOM was significant only in patients presenting with myelosuppression (HR: 3.34, 95% CI: 1.86-6.02) and not in patients without myelosuppression (HR: 0.71, 95% CI: 0.17-2.94, Interaction p-value< 0.01). The risk increased with higher dose density of rhG-CSF compared to rhG-CSF versus no users (p for trend< 0.001). CONCLUSION: These analyses indicate that rhG-CSF use is related to DOM following postoperative chemotherapy in NSCLC.

Optimal encephalitis/meningitis roadmap via precise diagnosis and treatment (IMPROVE): a study protocol for a randomized controlled trial.

BACKGROUND: Encephalitis/meningitis brings a heavy disease burden, and the origin of disease remains unknown in 30-40% of patients. It is greatly significant that combinations of nucleic acid amplification and autoimmune antibody testing improves the diagnosis and treatment of encephalitis/meningitis. Moreover, though several diagnostic methods are in clinical use, a recognized and unified diagnosis and treatment process for encephalitis management remains unclear. METHODS: IMPROVE is a multicenter, open label, randomized controlled clinical trial that aims to evaluate the diagnostic performance, applications, and impact on patient outcomes of a new diagnostic algorithm that combines metagenomic next-generation sequencing (mNGS), multiplex polymerase chain reaction (PCR) and autoimmune antibody testing. The enrolled patients will be grouped into two parallel groups, multiplex PCR test plus autoimmune antibody group (Group I) or the mNGS plus autoimmune antibody group (Group II) with a patient ratio of 1:1. Both groups will be followed up for 12 months. The primary outcomes include the initial time of targeted treatment and the modified Rankin scale score on the 30th day of the trial. The secondary outcomes are the cerebrospinal fluid index remission rate on the 14th day, mortality rate on the 30th day, and an evaluation of diagnostic efficacy. The two groups are predicted to comprise of 484 people in total. DISCUSSION: To optimize the roadmap of encephalitis/meningitis, precise diagnosis, and treatment are of great significance. The effect of rapid diagnosis undoubtedly depends on the progression of new diagnostic tests, such as the new multiplex PCR, mNGS, and examination of broad-spectrum autoimmune encephalitis antibodies. This randomized-controlled study could allow us to obtain an accurate atlas of the precise diagnostic ability of these tests and their effect on the treatment and prognosis of patients. Trial registration ClinicalTrial.gov, NCT04946682. Registered 29 June 2021, 'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT04946682?term=NCT04946682&draw=2&rank=1.

Corrigendum: The efficacy and safety analysis of first-line immune checkpoint inhibitors in pulmonary sarcomatoid carcinoma.

[This corrects the article DOI: 10.3389/fimmu.2022.956982.].

Antiviral Effect of Polyphenolic Substances in Geranium wilfordii Maxim against HSV-2 Infection Using in vitro and in silico Approaches.

Background: Herpes simplex virus type 2 (HSV-2) infestation was the most widespread STD (sexually transmitted diseases) among humans and was the leading cause of infectious recurrent genital herpes. Existing therapies against HSV-2 did incompletely restrain the comeback of activated HSV-2 infestation. Geranium wilfordii Maxim had long been used as traditional Chinese medicine for treating the diseases owing to its anti-inflammatory and antiviral effects. Herein, the study was designed to investigate the antiviral activity of G.wilfordii and its potential effect in regulating the host's immune response. Methods: To identify the stage of infection at which the compounds inhibited HSV-2, we performed virucidal, therapeutic, and prophylactic assays. The antiviral efficacy was evaluated by the analysis of viral components HSV-2 gD and VP16. The antiviral activities of these compounds were also evaluated by phenotypic analysis, such as cell proliferation and apoptosis. Molecular docking studies on candidate compounds were done to indicate binding interactions between the compounds and adopted compound targets. Results: Quercetin, corilagin, and geraniin inhibited the replication of HSV-2, with geraniin showing greater TI. The obtained IC50 value of quercetin was 204.7 µM and TI (IC50/EC50) was 5.1, whereas the obtained IC50 value of corilagin was 118.0 µg/ml and TI was 4.05. Geraniin exhibited prominent antiviral activity with an IC50 of 212.4 µM and an EC50 of 18.37 µM, resulting in a therapeutic index (TI) of 11.56. Geraniin showed important in vitro virucidal activity through blocking viral attachment. Compared with the virus group, the apoptosis rates in quercetin-, corilagin-, and geraniin-treated groups were significantly decreased (p < 0.001).The expressions at the transcription genes of virus own replication key factors (including HSV-2 gD and VP16) and cytokines (including TBK1) of infected cells treated with quercetin, corilagin, and geraniin were inhibited. The in silico approaches demonstrated a high number of potential strong intermolecular interactions as hydrogen bonds between geraniin, corilagin, and the activity site of HSV-2 gD. Molecular docking studies demonstrated the effects of corilagin by targeting TBK1. Conclusions: Together, these results highlighted the importance of G.wilfordii treatment in HSV-2 infection and underscored its therapeutic potential. However, additional in vitro and in vivo research was required to validate our findings.

Pan-cancer analysis of the FAM83 family and its association with prognosis and tumor microenvironment.

Family with sequence similarity 83 (FAM83) is a newly identified family of oncogenes whose members play important roles in signaling and cancer progression. However, a thorough understanding of the FAM83 family in tumors is still lacking. Here, we performed a comprehensive analysis of the expression levels of the FAM83 family across cancers and patient prognoses using bioinformatics methods. We found that the expression levels of FAM83 family genes were upregulated in most tumors, and importantly, high expression levels of FAM83 family genes were related to poor prognosis in most tumors. In addition, we analyzed the relationship of FAM83 family genes with immune subtypes and the tumor microenvironment (TME). The results showed that FAM83 family genes were significantly associated with immune infiltrative subtypes and to varying degrees with the level of stromal cell infiltration and tumor stem cells. Finally, our study also showed the relationship between FAM83 family genes and drug sensitivity. Therefore, this pan-cancer analysis demonstrates the critical role of FAM83 family genes in tumor development and provides new clues for therapeutic strategies for cancer.

The efficacy and safety analysis of first-line immune checkpoint inhibitors in pulmonary sarcomatoid carcinoma.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive disease without standardized treatment strategies. The efficacy of second-line or beyond immune checkpoint inhibitors (ICIs) has been proven in recent studies, whereas the evidence for first-line immunotherapy for PSC is still limited to case reports and remains poorly understood. Materials and methods: This was a multicenter, retrospective analysis of 21 patients with a histological diagnosis of PSC who received ICI as first-line therapy from January 2019 to March 2022. The expression of PD-L1 was evaluated by immunohistochemistry (IHC) using the monoclonal antibody 22C3. Low and high PD-L1 expressions were defined using the tumor proportion score (TPS), with cutoffs of 1 and 50%, respectively. Results: All eight patients had PD-L1 positivity who underwent PD-L1 expression assessment, and six patients (6/8, 75.0%) had high PD-L1 expression. Among the 21 PSC patients, seven received tislelizumab, six received camrelizumab, four received sintilimab, three received pembrolizumab, and one received durvalumab. Among them, 18 PSCs received combination therapy, whereas another three PSCs received immunotherapy alone. Out of the 21 PSC patients, 12 (57.1%) achieved a partial response (PR), and five patients had stable disease (SD) as the best response, whereas four PSCs experienced dramatic progressive disease (PD). The median progression-free survival (PFS) was 9.2 (95% CI [4.3, 14.1]) months, and the median OS was 22.8 (95% CI [4.0, 41.5]) months. Among the three treatment groups (immunotherapy alone, immunotherapy combined with anlotinib, and chemoimmunotherapy), the median PFS was 8.0, 9.4, and 9.6 months, and the median OS was 19.0, 22.8, and 30.6 months, respectively. There was no difference in PFS and OS between the three treatment regimen groups (P = 0.86 and P = 0.34, respectively) and different immunotherapies (P = 0.10 and P = 0.23, respectively). No serious adverse events (grade ≥ 3) were noted. Conclusion: First-line immunotherapy has promising therapeutic potential in the treatment of PSC. More studies are warranted to confirm these findings.

Survival and prognosis analyses of concurrent PIK3CA mutations in EGFR mutant non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors.

In non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation, the prognostic impact of a concurrent Phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA) mutation was still unknown. Some studies have shown that EGFR mutant NSCLC patients treated with EGFR tyrosine kinase inhibitors (TKIs) when concurrent PIK3CA mutation have a worse prognosis and shorter survival time. This study conducted a retrospective analysis of NSCLC patients with EGFR mutant or concurrent PIK3CA mutations from January 2015 to October 2019 in the First Affiliated Hospital of Nanchang University. Relative to EGFR alone mutations (Single-Mt), we found that NSCLC patients with EGFR mutations coexisting with PIK3CA mutations (Double-Mt) treated with EGFR-TKIs had a shorter median time to progression (TTP): 7.8 months versus 10.9 months (Double-Mt versus Single-Mt, P = 0.001), and decrease in median overall survival (OS): 20.6 months versus 32.4 months (P < 0.001). The objective response rate (ORR) between Double-Mt and Single-Mt was 36.7% versus 61.9% (P = 0.044), disease control rates (DCR) was 80.1% versus 91.7% (P = 0.179). Obviously, EGFR-TKIs for EGFR mutate NSCLC patients when concurrent PIK3CA mutations have a worse prognosis and shorter survival time.

A innovative prognostic symbol based on neutrophil extracellular traps (NETs)-related lncRNA signature in non-small-cell lung cancer.

Neutrophil extracellular traps (NETs) are closely related to cancer progression. NETs-related lncRNAs play crucial roles in non-small-cell lung cancer (NSCLC) but there have been no systematic studies regarding NETs-related long noncoding RNA (lncRNA) signatures to forecast the prognosis of NSCLC patients. It's essential to build commensurate NETs-related lncRNA signatures. The expression profiles of prognostic mRNAs and lncRNAs and relevant clinical data of NSCLC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The NETs-related genes came from the results of our transcriptome RNA microarray data. The co-expression network of lncRNAs and NETs-related genes was structured to confirm NETs-related lncRNAs. The 19 lncRNAs correlated with overall survival (OS) were selected by exploiting univariate Cox regression (P < 0.05). Lasso regression and multivariate Cox regression (P < 0.05) were utilized to develop a 12-NETs-related lncRNA signature. We established a risk score based on the signature, which suggested that patients in the high-risk group displayed significantly shorter OS than patients in the low-risk group (P < 0.0001, P = 0.0023 respectively in the two cohorts). The risk score worked as an independent predictive factor for OS in both univariate and multivariate Cox regression analyses (HR> 1, P< 0.001). Additionally, by RT-qPCR, we confirmed that NSCLC cell lines have higher levels of the three adverse prognostic NETs-related lncRNAs than normal lung cells. The expression of lncRNAs significantly increases after NETs stimulation. In short, the 12 NETs-related lncRNAs and their model could play effective roles as molecular markers in predicting survival for NSCLC patients.

CCL19 and CCR7 Expression, Signaling Pathways, and Adjuvant Functions in Viral Infection and Prevention.

Chemokine (C-C motif) ligand 19 (CCL19) is a critical regulator of the induction of T cell activation, immune tolerance, and inflammatory responses during continuous immune surveillance, homeostasis, and development. Migration of CC-chemokine receptor 7 (CCR7)-expressing cells to secondary lymphoid organs is a crucial step in the onset of adaptive immunity, which is initiated by a complex interaction between CCR7 and its cognate ligands. Recent advances in knowledge regarding the response of the CCL19-CCR7 axis to viral infections have elucidated the complex network of interplay among the invading virus, target cells and host immune responses. Viruses use various strategies to evade or delay the cytokine response, gaining additional time to replicate in the host. In this review, we summarize the impacts of CCL19 and CCR7 expression on the regulation of viral pathogenesis with an emphasis on the corresponding signaling pathways and adjuvant mechanisms. We present and discuss the expression, signaling adaptor proteins and effects of CCL19 and CCR7 as these molecules differentially impact different viral infections and viral life cycles in host homeostatic strategies. The underlying mechanisms discussed in this review may assist in the design of novel agents to modulate chemokine activity for viral prevention.

Evaluation of Epstein-Barr Virus Salivary Shedding in HIV/AIDS Patients and HAART Use: A Retrospective Cohort Study.

Little data is available on the evaluation of the occurrence rates of Epstein-Barr virus (EBV) in saliva and relationship with highly active antiretroviral therapy (HAART) use in HIV/AIDS patients in China. We conducted a retrospective cohort study of EBV serological tests for HIV/AIDS patients who were treated in the hospitals for infectious diseases in Wuxi and Shanghai, China from May 2016 to April 2017. The EBV-seropositive samples were identified by ELISA. EBV-specific primers and probes were used for the quantitative detection of viral DNA from saliva via quantitative real-time polymerase chain reaction. CD4 cell counts of the HIV/AIDS patients were detected by a flow cytometry. A total of 372 HIV/AIDS patients were ultimately selected and categorized for this retrospective cohort study. For EBV IgG and IgM, the HIV/AIDS HAART use (H) and non-HAART use (NH) groups had significantly higher seropositive rates than the HIV-negative control group. The HIV/AIDS (NH) group had the highest seropositive rate (IgG, 94.27%; IgM, 68.98%) and the highest incidence of EBV reactivation or infection. For salivary EBV DNA-positive rates and quantities, the HIV/AIDS (H) (73.69%) and the HIV/AIDS (NH) (100%) groups showed significantly higher values than the HIV-negative control group (35.79%, > twofold). Further, the salivary EBV DNA-negative population had significantly higher CD4 cell counts than the EBV DNA-positive population in the HIV/AIDS (H) group and the HIV/AIDS (NH) groups. Thus, HAART use is beneficial in decreasing the EBV salivary shedding in HIV/AIDS patients and indirectly decreases EBV transmission risk.

Prevalence and determinants of HIV in tuberculosis patients in Wuxi City, Jiangsu province, China: a cross-sectional study.

At least one-third of the 34 million people living with human immunodeficiency virus (HIV) worldwide are infected with latent tuberculosis (TB). The aim of this study was to determine the rate of HIV infection in TB patients and its determinants in Wuxi City, China. TB patients attending health institutions (12 selected sites) for TB diagnosis and treatment were enrolled in this study. TB diagnosis, treatment and HIV testing were done according to the national guidelines. Blood samples were collected for anonymous HIV testing. Among the TB patients, the HIV prevalence was 13.66% (1493/10,926). Multivariate analysis showed that gender, age, education, marital status, per capita monthly income, patient residence, family size, distance from a health institution, knowledge of HIV-TB co-infection, and knowledge of HIV may be risk factors for HIV-TB co-infection (all: odds ratio > 1, p < 0.05). The prevalence of TB in those with HIV was higher among the study participants. Improving public awareness of HIV-TB co-infection, regularly screening and improving follow-up can reduce the occurrence of HIV-TB co-infection.