BACKGROUND: As the efficacy of programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors combined with chemotherapy in curing breast cancer is still controversial, this meta-analysis compares the efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy alone in the treatment of breast cancer, which provides guidance for the clinical treatment. METHODS: Relevant studies published as of April 2022 in the various databases including EMBASE, PubMed, and Cochrane Library were selected. Randomized controlled trials (RCTs) in which control patients underwent chemotherapy alone and experimental group patients underwent combination chemotherapy and PD-1/PD-L1 inhibitor treatment were included in this investigation. Investigations without complete information, researches from which information could not be extracted, duplicate articles, animal studies, review articles, and systematic reviews were excluded. STATA 15.1 was employed for all statistical analyses. RESULTS: In total, eight eligible studies were identified, revealing that combination chemotherapy and PD-1/PD-L1 inhibitor treatment was linked to significant increases in progression-free survival (PFS) relative to chemotherapy alone (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.70-0.99, P = 0.032) but not overall survival (HR = 0.92, 95% CI: 0.80-1.06, P = 0.273). Pooled adverse event rates were also increased within the group of combination treatment relative to the chemotherapy group (risk ratio [RR] = 1.08, 95% CI: 1.03-1.14, P = 0.002). Specifically, nausea rates were lesser within the group of combination treatment relative to the group of chemotherapy (RR = 0.48, 95% CI: 0.25-0.92, P = 0.026). Subgroup analyses indicated that the PFS of patients who underwent combination atezolizumab or pembrolizumab and chemotherapy treatment were substantially longer than those of patients who underwent chemotherapy alone (HR = 0.79, 95% CI: 0.69-0.89, P ≤0.001; HR = 0.79, 95% CI: 0.67-0.92, P = 0.002). CONCLUSIONS The pooled results suggest that combination chemotherapy and PD-1/PD-L1 inhibitor treatment approaches help prolong PFS in breast cancer patients, but have no statistically significant effect on overall survival (OS). Additionally, combination therapy can significantly improve complete response rate (CRR) compared with chemotherapy alone. However, combination therapy was associated with greater rates of adverse events.
Humans ; B7-H1 Antigen/antagonists & inhibitors* ; Drug Therapy, Combination ; Immune Checkpoint Inhibitors/therapeutic use* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Breast Neoplasms/drug therapy*

Primary aldosteronism (PA) is the most common form of secondary hypertension, with its main manifestations including hypertension and hypokalemia. Early identification of PA is extremely important as PA patients can easily develop cardiovascular complications such as atrial fibrillation, stroke, and myocardial infarction. The past decade has witnessed the rapid advances in the genetics of PA, which has shed new light on PA treatment. While surgery is the first choice for unilateral diseases, bilateral lesions can be treated with mineralocorticoid receptor antagonists (MRAs). The next-generation non-steroidal MRAs are under investigations. New medications including calcium channel blockers, macrophage antibiotics, and aldosterone synthase inhibitors have provided a new perspective for the medical treatment of PA.
Humans ; Hyperaldosteronism/complications* ; Adrenalectomy/adverse effects* ; Aldosterone/therapeutic use* ; Hypertension/drug therapy* ; Mineralocorticoid Receptor Antagonists/therapeutic use*

Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.
Male ; Humans ; Prostatic Neoplasms/chemically induced* ; Androgen Antagonists/adverse effects* ; COVID-19 ; Androgens/therapeutic use* ; SARS-CoV-2

Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.
Humans ; Male ; Androgen Antagonists/therapeutic use* ; Androgens/metabolism* ; Hepatocyte Nuclear Factor 3-alpha/metabolism* ; Mutation ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Receptors, Androgen/metabolism*

CUDC-101, an effective and multi-target inhibitor of epidermal growth factor receptor (EGFR), histone deacetylase (HDAC), and human epidermal growth factor receptor 2 (HER2), has been reported to inhibit many kinds of cancers, such as acute promyelocytic leukemia and non-Hodgkin's lymphoma. However, no studies have yet investigated whether CUDC-101 is effective against myeloma. Herein, we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma (MM) cell lines and induces cell apoptosis in a time- and dose-dependent manner. Moreover, CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase (PI3K) and HDAC, and regulated the cell cycle G2/M arrest. Moreover, we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug. Bortezomib is one of the important drugs in MM treatment, and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib. The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade. Collectively, our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib, which provides insights into exploring new strategies for MM treatment.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; Bortezomib/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; ErbB Receptors/antagonists & inhibitors* ; G2 Phase Cell Cycle Checkpoints ; Histone Deacetylase Inhibitors/pharmacology* ; Histone Deacetylases/metabolism* ; M Cells ; Multiple Myeloma/drug therapy*

We aimed to study radiomics approach based on biparametric magnetic resonance imaging (MRI) for determining significant residual cancer after androgen deprivation therapy (ADT). Ninety-two post-ADT prostate cancer patients underwent MRI before prostatectomy (62 with significant residual disease and 30 with complete response or minimum residual disease [CR/MRD]). Totally, 100 significant residual, 52 CR/MRD lesions, and 70 benign tissues were selected according to pathology. First, 381 radiomics features were extracted from T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps. Optimal features were selected using a support vector machine with a recursive feature elimination algorithm (SVM-RFE). Then, ADC values of significant residual, CR/MRD lesions, and benign tissues were compared by one-way analysis of variance. Logistic regression was used to construct models with SVM features to differentiate between each pair of tissues. Third, the efficiencies of ADC value and radiomics models for differentiating the three tissues were assessed by area under receiver operating characteristic curve (AUC). The ADC value (mean ± standard deviation [s.d.]) of significant residual lesions ([1.10 ± 0.02] × 10^-3 mm² s^-1) was significantly lower than that of CR/MRD ([1.17 ± 0.02] × 10^-3 mm² s^-1), which was significantly lower than that of benign tissues ([1.30 ± 0.02] × 10^-3 mm² s^-1; both P < 0.05). The SVM feature models were comparable to ADC value in distinguishing CR/MRD from benign tissue (AUC: 0.766 vs 0.792) and distinguishing residual from benign tissue (AUC: 0.825 vs 0.835) (both P > 0.05), but superior to ADC value in differentiating significant residual from CR/MRD (AUC: 0.748 vs 0.558; P = 0.041). Radiomics approach with biparametric MRI could promote the detection of significant residual prostate cancer after ADT.
Male ; Humans ; Prostatic Neoplasms/drug therapy* ; Androgen Antagonists/therapeutic use* ; Androgens ; Neoplasm, Residual ; Retrospective Studies ; Magnetic Resonance Imaging/methods* ; Diffusion Magnetic Resonance Imaging/methods*

Male ; Humans ; Prostatic Neoplasms/pathology* ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Hormones ; Androgen Antagonists/therapeutic use*

OBJECTIVES: The use of anticholinergic drugs in the elderly may lead to negative events such as falls, delirium, urinary retention and cognitive decline, and the higher the number of anticholinergic drugs use, the more such negative events occur. This study aims to analyze the risk factors associated with the prescription of total anticholinergic drugs in elderly outpatients and evaluate the rationality of anticholinergic drugs, and to provide a reference for reducing the adverse effects of anticholinergic drugs. METHODS: A list of drugs with anticholinergic activity based on the Beers criteria was established. The basic information (such as age and gender), clinical diagnosis, and medications of elderly outpatient were extracted from hospital electronic medical records, and the Anticholinergic Cognitive Burden (ACB) Scale was used to calculate the anticholinergic burden for each patient. Logistic regression analysis was used to identify the potential risk factors for the occurrence of problems such as multiple medication and insomnia. RESULTS: A total of 1 840 prescriptions for elderly patients were reviewed. Of these patients, ACB score was more than or equal to 1 in 648 (35.22%) patients. Number of prescription medication (95% CI: 1.221 to 1.336) and insomnia (95% CI: 3.538 to 6.089) were independent factors affecting ACB scores (both P<0.01). Medications for patients of ACB scores were most commonly treated with the central nervous system drugs (such as alprazolam and eszopiclone) and for the cardiovascular system drugs (such as metoprolol and nifedipine). CONCLUSIONS There is a high rate of ACB drugs use in geriatric patients, and the clinical focus should be on multiple medication prescriptions, especially on the central nervous system drugs (such as alprazolam and eszopiclone) and cardiovascular system drugs (such as metoprolol and nifedipine). The prescription review should be emphasized to reduce adverse reactions to anticholinergic drugs in elderly patients.
Humans ; Aged ; Cholinergic Antagonists/adverse effects* ; Outpatients ; Metoprolol ; Alprazolam ; Eszopiclone ; Nifedipine ; Sleep Initiation and Maintenance Disorders ; Risk Factors

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

Purinergic P2Y Receptor Antagonists ; Consensus ; Cardiovascular System ; Cardiology ; Asia