Real-World Efficacy and Safety of Durvalumab Administration Following Chemoradiotherapy in Elderly Patients With Unresectable Locally Advanced Nonsmall Cell Lung Cancer: A Multicenter, Retrospective Study.

BACKGROUND: The PACIFIC trial established durvalumab administration after chemoradiotherapy as the standard of care for unresectable locally advanced nonsmall cell lung cancer (LA-NSCLC). However, the efficacy and safety of durvalumab in elderly patients aged 75 years or above remains unclear. This study aimed to investigate the real-world efficacy and safety of durvalumab for LA-NSCLC, with a specific focus on elderly patients. PATIENTS AND METHODS: We reviewed 214 patients who received durvalumab out of 278 patients with unresectable LA-NSCLC who underwent chemoradiotherapy at 7 institutions between July 2018 and March 2022. Propensity score matching (PSM) analysis was performed to evaluate the efficacy of durvalumab in elderly patients. RESULTS: The 2-year progression-free survival (PFS) and 2-year overall survival (OS) rates were 42.2% (95% confidence interval [CI], 34.7%-49.5%) and 77.1% (95% CI, 70.1-82.7%), respectively. Grade ≥ 3 immune-related adverse events (irAEs) occurred in 8.2% of patients. PSM analysis revealed that OS was significantly shorter in elderly patients (≥ 75 years) than in younger patients (< 75 years) (hazard ratio [HR]; 95% CI, 1.39-8.99; P = .008), whereas PFS did not differ significantly between the 2 groups (HR: 1.50, 95% CI, 0.84-2.68, P = .169). The frequency of irAEs did not differ between these groups. CONCLUSIONS: The real-world efficacy and safety of durvalumab administration following chemoradiotherapy for LA-NSCLC coincided with the PACIFIC trial's findings. Disease control achieved with this protocol did not differ significantly between elderly and younger patients but had acceptable tolerability, demonstrating its benefit even in elderly LA-NSCLC patients aged 75 years or above.

SF6 is a useful expander for post-pneumonectomy syndrome in the long-term course: a case report.

BACKGROUND: Post-pneumonectomy syndrome (PPS) is a rare but serious condition that can occur after pneumonectomy. It is characterized by a mediastinal shift towards the vacated hemithorax, which can potentially lead to respiratory failure. The management of PPS poses a clinical challenge, especially in the context of the limited availability of certain therapeutic devices due to regulatory restrictions in Japan. CASE PRESENTATION: A 36-year-old female with stage IB non-small cell lung cancer underwent left pneumonectomy. Approximately 2 years later, she developed dyspnea. After consulting with our hospital, subsequent imaging revealed an extreme mediastinal shift causing bronchial obstruction. Emergency thoracotomy and subsequent sulfur hexafluoride (SF6) injections were successfully used to manage her condition. Over the course of follow-up, the interval between SF6 injections was extended from 3 to 11 months, indicating an improvement in the intrathoracic condition. CONCLUSIONS: This case illustrates the efficacy of SF6 gas in treating PPS and in reducing the frequency of medical interventions. SF6 gas administration is safe and effective for the treatment of patients with PPS.

The Role of Zinc in the Development of Vascular Dementia and Parkinson's Disease and the Potential of Carnosine as Their Therapeutic Agent.

Synaptic zinc ions (Zn2+) play an important role in the development of vascular dementia (VD) and Parkinson's disease (PD). In this article, we reviewed the current comprehension of the Zn2+-induced neurotoxicity that leads to the pathogenesis of these neuronal diseases. Zn2+-induced neurotoxicity was investigated by using immortalised hypothalamic neurons (GT1-7 cells). This cell line is useful for the development of a rapid and convenient screening system for investigating Zn2+-induced neurotoxicity. GT1-7 cells were also used to search for substances that prevent Zn2+-induced neurotoxicity. Among the tested substances was a protective substance in the extract of Japanese eel (Anguilla japonica), and we determined its structure to be like carnosine (ß-alanylhistidine). Carnosine may be a therapeutic drug for VD and PD. Furthermore, we reviewed the molecular mechanisms that involve the role of carnosine as an endogenous protector and its protective effect against Zn2+-induced cytotoxicity and discussed the prospects for the future therapeutic applications of this dipeptide for neurodegenerative diseases and dementia.

Cytomegalovirus cavitary pneumonia in a human immunodeficiency virus-infected patient.

Cavitary lung lesions are uncommon radiological findings in cytomegalovirus pneumonia, and tissue biopsy is rarely performed for diagnosis. A 67-year-old man presented with a wet cough. Extensive white moss in the oral cavity was found on physical examination, and chest computed tomography revealed an approximately 4 cm cavitary lesion in the upper lobe of the right lung. Blood tests showed a critically low CD4+ T lymphocyte count and positivity for human immunodeficiency virus type 1 antibodies. A transbronchial biopsy of the cavitary lung lesion was performed, and inclusion bodies in the nuclei of enlarged alveolar epithelial cells were seen in the histopathological findings. Immunohistochemistry staining for cytomegalovirus was positive, and cytomegalovirus pneumonia was diagnosed. Ganciclovir treatment was initiated, and the symptoms and imaging findings resolved. Cytomegalovirus pneumonia can present as cavitary lung lesions in patients with acquired immunodeficiency syndrome, and a transbronchial biopsy is essentially useful for a definitive diagnosis.

Current perspectives of viral hepatitis.

Viral hepatitis represents a major danger to public health, and is a globally leading cause of death. The five liver-specific viruses: Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus, each have their own unique epidemiology, structural biology, transmission, endemic patterns, risk of liver complications, and response to antiviral therapies. There remain few options for treatment, in spite of the increasing prevalence of viral-hepatitis-caused liver disease. Furthermore, chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality, even though effective treatments are available that could reduce or prevent most patients' complications. In 2016, the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030, along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis. Today, treatment is sufficiently able to prevent the disease from reaching advanced phases. However, future therapies must be extremely safe, and should ideally limit the period of treatment necessary. A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis. This review aims to summarize the current state of knowledge on each type of viral hepatitis, together with major innovations.

Primary mediastinal choriocarcinoma requiring differentiation from non-small cell lung cancer: An autopsy case report.

A 65-year-old man with dyspnea and hemoptysis presented with a right upper lobe mass associated with enlarged mediastinal lymph nodes and bilateral pulmonary nodules on chest computed tomography (CT), suspected lung cancer. Bronchial and CT-guided biopsies revealed poorly differentiated carcinoma. His condition deteriorated rapidly before a definitive diagnosis could be made. Autopsy revealed primary mediastinal choriocarcinoma. Primary mediastinal choriocarcinomas are rare, difficult to diagnose early and have a poor prognosis. In patients with a tumor expanding across the lung and mediastinum and exhibiting pathologic findings of a pooly differentiated carcinoma, we should consider choriocarcinoma, evaluating the serum ß-human chorionic gonadotropin levels.

The copy number of the eukaryotic rRNA gene can be counted comprehensively.

Gene sequence has been widely used in molecular ecology. For instance, the ribosomal RNA (rRNA) gene has been widely used as a biological marker to understand microbial communities. The variety of the detected rRNA gene sequences reflects the diversity of the microorganisms existing in the analyzed sample. Their biomass can also be estimated by applying quantitative sequencing with information on rRNA gene copy numbers in genomes; however, information on rRNA gene copy numbers is still limited. Especially, the copy number in microbial eukaryotes is much less understood than that of prokaryotes, possibly because of the large and complex structure of eukaryotic genomes. In this study, we report an alternative approach that is more appropriate than the existing method of quantitative sequencing and demonstrate that the copy number of eukaryotic rRNA can be measured efficiently and comprehensively. By applying this approach widely, information on the eukaryotic rRNA copy number can be determined, and their community structures can be depicted and compared more efficiently.

Detecting acquired V-Raf murine sarcoma viral oncogene homolog B1 V600E mutation associated with osimertinib resistance in epidermal growth factor receptor-mutant lung adenocarcinoma: A case report.

Osimertinib has demonstrated efficacy as the first- and second-line treatment for advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations. However, EGFR-mutant NSCLC cells often acquire resistance to osimertinib. V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation (BRAF V600E) was detected in a re-biopsy (LC-SCRUM-TRY testing) of a patient with advanced lung adenocarcinoma who was resistant to osimertinib treatment. Currently, the patient is receiving dabrafenib/trametinib combination therapy and is under observation; a slight shrinking effect of cancer has been observed.

Effect of Tegafur-Uracil in Resected Stage IB Lung Adenocarcinoma According to Presence or Absence of Epidermal Growth Factor Receptor Gene Mutation: A Retrospective Cohort Study.

PURPOSE: Tegafur-uracil (UFT) is the standard postoperative adjuvant therapy for stage IB lung adenocarcinoma (LUAD) in Japan. This study aimed to determine whether UFT is effective in stage IB LUAD with and without epidermal growth factor receptor (EGFR) mutations. METHODS: This retrospective study included 169 patients with stage IB LUAD who underwent complete resection at our department between 2010 and 2021. We investigated the clinicopathological and prognostic impact of EGFR mutations as well as the postoperative use of UFT. RESULTS: EGFR mutation-positive cases tended to show a higher cumulative recurrence rate than EGFR mutation-negative cases (p = 0.081), while overall survival was comparable between the groups (p = 0.238). In the entire cohort, UFT administration was not an independent prognostic factor in the multivariate regression analysis (p = 0.112). According to a stratification analysis, UFT administration was independently associated with favorable overall survival (p = 0.031) in EGFR mutation-negative cases, while it was not associated with recurrence-free survival (p = 0.991) or overall survival (p = 0.398) in EGFR mutation-positive cases. CONCLUSION: UFT administration can improve the prognosis of EGFR mutation-negative LUAD but not EGFR mutation-positive LUAD. Thus, clinical trials of adjuvant-targeted therapy for EGFR mutation-positive stage IB LUAD should also be conducted in Japan.

COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron.

Identification of Tumor-Suppressive miR-139-3p-Regulated Genes: TRIP13 as a Therapeutic Target in Lung Adenocarcinoma.

Analyses of our microRNA (miRNA) expression signature combined with The Cancer Genome Atlas (TCGA) data revealed that both strands of pre-miR-139 (miR-139-5p, the guide strand, and miR-139-3p, the passenger strand) are significantly downregulated in lung adenocarcinoma (LUAD) clinical specimens. Functional analyses of LUAD cells ectopically expressing miR-139-3p showed significant suppression of their aggressiveness (e.g., cancer cell proliferation, migration, and invasion). The involvement of the passenger strand, miR-139-3p, in LUAD pathogenesis, is an interesting finding contributing to the elucidation of unknown molecular networks in LUAD. Of 1108 genes identified as miR-139-3p targets in LUAD cells, 21 were significantly upregulated in LUAD tissues according to TCGA analysis, and their high expression negatively affected the prognosis of LUAD patients. We focused on thyroid hormone receptor interactor 13 (TRIP13) and investigated its cancer-promoting functions in LUAD cells. Luciferase assays showed that miR-139-3p directly regulated TRIP13. siRNA-mediated TRIP13 knockdown and TRIP13 inhibition by a specific inhibitor (DCZ0415) attenuated the malignant transformation of LUAD cells. Interestingly, when used in combination with anticancer drugs (cisplatin and carboplatin), DCZ0415 exerted synergistic effects on cell proliferation suppression. Identifying the molecular pathways regulated by tumor-suppressive miRNAs (including passenger strands) may aid in the discovery of diagnostic markers and therapeutic targets for LUAD.

Secondary pulmonary infection by Fusarium solani and Aspergillus niger during systemic steroid treatment for COVID-19: A case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-associated invasive pulmonary aspergillosis presents a diagnostic challenge due to its non-specific clinical/ imaging features, as well as the fact that the proposed clinically diagnostic algorithms do not necessarily apply to COVID-19 patients. In addition, Fusarium spp. is a rare cause of opportunistic life-threatening fungal infections. Disseminated Fusarium infection in an immunocompromised host is intractable, with a high likelihood of resulting mortality. To our knowledge, this is the first case of secondary pulmonary infection by Fusarium solani (F. solani) and Aspergillus niger (A. niger) during systemic steroid treatment for COVID-19. CASE SUMMARY: A 62-year-old male was transported to our hospital by ambulance with a complaint of fever and dyspnea. We established a diagnosis of pneumococcal pneumonia, complicated with COVID-19 and septic shock, together with acute renal failure. He was admitted to the intensive care unit, to be treated with piperacillin/tazobactam, vancomycin, and 6.6 mg per day of dexamethasone sodium phosphate, along with noradrenaline as a vasopressor, ventilator management, and continuous hemodiafiltration. His condition improved, and we finished the vasopressor on the fifth hospital day. We administered dexamethasone for ten days, and finished the course of treatment. On the eleventh day, patient respiratory deterioration was observed, and a computed tomography scan showed an exacerbation of bilateral ground-glass-opacity-like consolidation, together with newly appeared cavitary lesions in the lung. we changed antibiotics to meropenem plus vancomycin. In addition, a fungal infection was considered as a possibility based on microscopic findings of sputum, and we began coadministration of voriconazole. However, the pneumonia worsened, and the patient died on the seventeenth day of illness. Later, F. solani and A. niger were identified from sputum collected on the twelfth day. It was believed that he developed a cell-mediated immune deficiency during COVID-19 treatment, which led to the complication of pneumonia caused by the above-mentioned fungi, contributing to his death. CONCLUSION: Because early initiation of intense antifungal therapy offers the best chance for survival in pulmonary fusariosis, computed tomography scans and appropriate microbiologic investigations should be obtained for severely immunocompromised patients.

Penile and scrotal strangulation by stainless steel rings in an human immunodeficiency virus positive man: A case report.

BACKGROUND: Penoscrotal constriction devices are either used as autoerotic stimuli or to increase sexual pleasure or performance by maintaining an erection for a longer period, and a variety of metallic and non-metallic objects are used. On the other hand, penile strangulation is a rare urologic emergency that requires prompt evaluation and intervention to prevent long-term complications. The goal of treating penile incarceration is to remove the foreign object as soon as possible. On the other hand, removal can be very challenging, and often requires resourcefulness and a multidisciplinary approach. CASE SUMMARY: A 47-year-old man who has sex with men was transferred to our hospital for persistent phallodynia and scrotal pain, accompanying swelling due to strangulation by stainless steel rings. His medical history included acquired immunodeficiency syndrome. One day prior, he had put three stainless steel rings on his penis and scrotum before sexual intercourse. After sexual intercourse, he was unable to remove them, due to swelling of his penis and scrotum. The swelling persisted, and he felt pain in the affected area the next day, then he was transferred to our hospital by ambulance. The emergency department found that his penis and scrotum were markedly engorged and swollen. We established a diagnosis of penile and scrotal strangulation by stainless steel rings. We unsuccessfully attempted to cut the rings using a cutter, then requested a rescue team via emergency medical service. They cut through each ring in two places, using an electric-powered angle grinder, and successfully removed all of the pieces. Finally, he was discharged and went home. CONCLUSION: We report the first case of penile and scrotal strangulation by stainless steel rings in an human immunodeficiency virus positive person.

Toxic Effects of Two Redox States of Thallium on Immortalised Hypothalamic GT1-7 Neuronal Cells.

Thallium (Tl), is a highly toxic heavy metal that exists in monovalent (Tl(I)) and trivalent (Tl(III)) ionic states. This study aimed to compare the toxicities of Tl(I) and Tl(III) in a mouse hypothalamic GT1-7 neuronal cell line. Decreased viability and increased cytotoxicity were observed in the GT1-7 cells 16 h after Tl(I) or Tl(III) treatment. Tl(III) was more cytotoxic, than Tl(I), as indicated by extracellular lactate dehydrogenase levels. Both treatments induced caspase 3 activity, DNA fragmentation, malondialdehyde (MDA) production, and superoxide dismutase activity in the cells. MDA production was higher after Tl(III) than after Tl(I) treatment. Moreover, co-treatment with antioxidants, such as mannitol, ascorbic acid, or tocopherol, significantly attenuated the Tl-induced decrease in GT1-7 cell numbers. Therefore, both treatments induced oxidative stress-related apoptosis. Furthermore, Tl(III) reduced the cell viability more subtly than Tl(I) after 1 and 3 h of treatment. This effect was enhanced by co-treatment with maltol or citric acid, which promoted the influx of metallic elements into the cells. Thus, Tl(III) entered GT1-7 cells later than Tl(I) and had a delayed onset of toxicity. However, Tl(III) likely produces more extracellular lipid peroxides, which may explain its stronger cytotoxicity.

The Molecular Pathogenesis of Tumor-Suppressive miR-486-5p and miR-486-3p Target Genes: GINS4 Facilitates Aggressiveness in Lung Adenocarcinoma.

The involvement of passenger strands of miRNAs in the molecular pathogenesis of human cancers is a recent concept in miRNA research, and it will broaden our understanding of the molecular mechanisms of miRNA-mediated cancer. The analysis of our miRNA signature of LUAD revealed that both strands of pre-miR-486 (miR-486-5p and miR-486-3p) were downregulated in LUAD tissues. Ectopic expression of both miRNAs induced cell cycle arrest in LUAD cells, suggesting both strands of miRNAs derived from pre-miR-486 were tumor suppressive. Our in silico analysis showed a total of 99 genes may be under the control of both miRNAs in LUAD cells. Importantly, among these targets, the high expression of seven genes (MKI67, GINS4, RRM2, HELLS, MELK, TIMELESS, and SAPCD2) predicted a poorer prognosis of LUAD patients (p < 0.05). We focused on GINS4, a DNA replication complex GINS protein that plays an essential role in the initiation of DNA replication. Our functional assays showed that GINS4 was directly controlled by both strands of pre-miR-486, and its aberrant expression facilitated the aggressive behavior of LUAD cells. GINS4 is attractive as a therapeutic target for this disease. MiRNA analysis, including passenger strands, will further improve our understanding of the molecular pathogenesis of LUAD.

Minichromosome maintenance proteins in lung adenocarcinoma: Clinical significance and therapeutic targets.

Lung cancer is the most common cause of cancer-related death worldwide, accounting for 1.8 million deaths annually. Analysis of The Cancer Genome Atlas data showed that all members of the minichromosome maintenance (MCM) family (hexamers involved in DNA replication: MCM2-MCM7) were upregulated in lung adenocarcinoma (LUAD) tissues. High expression of MCM4 (P = 0.0032), MCM5 (P = 0.0032), and MCM7 (P = 0.0110) significantly predicted 5-year survival rates in patients with LUAD. Simurosertib (TAK-931) significantly suppressed the proliferation of LUAD cells by inhibiting cell division cycle 7-mediated MCM2 phosphorylation. This finding suggested that MCM2 might be a therapeutic target for LUAD. Moreover, analysis of the epigenetic regulation of MCM2 showed that miR-139-3p, miR-378a-5p, and miR-2110 modulated MCM2 expression in LUAD cells. In patients with LUAD, understanding the role of these miRNAs may improve prognoses.

High doses of dextromethorphan induced shock and convulsions in a 19-year-old female: A case report.

BACKGROUND: Dextromethorphan is a prevalent antitussive agent that can be easily obtained as an over-the-counter medication. There has been a growing number of reported cases of toxicity in recent years. Generally, there are numerous instances of mild symptoms, with only a limited number of reports of severe cases necessitating intensive care. We presented the case of a female who ingested 111 tablets of dextromethorphan, leading to shock and convulsions and requiring intensive care that ultimately saved her life. CASE SUMMARY: A 19-year-old female was admitted to our hospital via ambulance, having overdosed on 111 tablets of dextromethorphan (15 mg) obtained through an online importer in a suicide attempt. The patient had a history of drug abuse and multiple self-inflicted injuries. At the time of admission, she exhibited symptoms of shock and altered consciousness. However, upon arrival at the hospital, the patient experienced recurrent generalized clonic convulsions and status epilepticus, necessitating tracheal intubation. The convulsions were determined to have been caused by decreased cerebral perfusion pressure secondary to shock, and noradrenaline was administered as a vasopressor. Gastric lavage and activated charcoal were also administered after intubation. Through systemic management in the intensive care unit, the patient's condition stabilized, and the need for vasopressors ceased. The patient regained consciousness and was extubated. The patient was subsequently transferred to a psychiatric facility, as suicidal ideation persisted. CONCLUSION: We report the first case of shock caused by an overdose of dextromethorphan.

The Functional Role of Group 2 Innate Lymphoid Cells in Asthma.

Asthma is a heterogeneous disease characterized by chronic airway inflammation. Group 2 innate lymphoid cells (ILC2) play an important role in the pathogenesis of asthma. ILC2s lack antigen-specific receptors and respond to epithelial-derived cytokines, leading to the induction of airway eosinophilic inflammation in an antigen-independent manner. Additionally, ILC2s might be involved in the mechanism of steroid resistance. Numerous studies in both mice and humans have shown that ILC2s induce airway inflammation through inflammatory signals, including cytokines and other mediators derived from immune or non-immune cells. ILC2s and T helper type 2 (Th2) cells collaborate through direct and indirect interactions to organize type 2 immune responses. Interestingly, the frequencies or numbers of ILC2 are increased in the blood and bronchoalveolar lavage fluid of asthma patients, and the numbers of ILC2s in the blood and sputum of severe asthmatics are significantly larger than those of mild asthmatics. These findings may contribute to the regulation of the immune response in asthma. This review article highlights our current understanding of the functional role of ILC2s in asthma.

Diagnostic utility of fine-needle aspiration cytology in syphilitic lymphadenitis: A case report.

Syphilis is a sexually transmitted infection that causes serious health problems without treatment. Detection of syphilis is necessary to stop the spread of the infection. Cytological screeners and pathologists may experience fine-needle aspiration cytology (FNAC) for syphilitic lymphadenitis; however, its characteristic cytological features are rarely reported. We present FNAC cytological features of syphilitic lymphadenitis in a case of a 21-year-old man. He presented with a sore throat and painful neck lymphadenopathy. His swollen and painful neck persisted even with antibiotic treatment. Necrotizing lymphadenitis and lymphoma were clinically suspected. FNAC was taken from the swollen lymph node. Cytologic findings of the specimen showed various inflammatory cells with small-sized vessels arranged in a branching/arborizing fashion. The vessels were surrounded by inflammatory cells, including plasma cells, neutrophils, and macrophages. Perivascular plasma cell cuffing was focally seen along with inconspicuous granulomas. Neutrophils appeared to involve the vascular wall. The cytological findings suggested syphilitic lymphadenitis, and clinical findings and serological tests confirmed primary syphilis with concomitant human immunodeficiency virus infection. Branching/arborizing vessels associated with many plasma cells, vascular involvement of neutrophils, and granulomas may suggest syphilitic infection if the specimen is obtained via FNAC. (189 words).

MiR-15b-5p inhibits castration-resistant growth of prostate cancer cells by targeting the muscarinic cholinergic receptor CHRM3.

Cholinergic receptor muscarinic 3 (CHRM3)-mediated focal adhesion kinase/YES-associated protein (YAP) signalling is essential for the growth of castration-resistant prostate cancer (CRPC) cells. Here, we evaluated the molecular mechanisms through which CHRM3 overexpression facilitates castration-resistant growth. Small RNA sequencing combined with in silico analyses revealed that CHRM3 was a putative target of miR-15b-5p. Notably, androgen deprivation suppressed miR-15b-5p expression and increased CHRM3 expression. Moreover, miR-15b-5p bound directly to CHRM3 and inhibited YAP activation induced by CHRM3 stimulation. Furthermore, miR-15b-5p abolished the growth of CRPC cells induced by CHRM3 stimulation. We conclude that the miR-15b-5p/CHRM3/YAP signalling axis promotes the castration-resistant growth of prostate cancer.