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Prostate cancer is one of the most common malignancies in men. Calcium signaling is implicated in the progression of prostate cancer and plays a critical role in immune cell function. However, whether specific calcium channel-related genes play a crucial role in the immune cell infiltration levels of prostate cancer requires further research. In this study, we performed an integrated analysis of transcriptional, clinical, and somatic mutation data from The Cancer Genome Atlas database and identified the hub calcium channel-related gene P2RX2 to be associated with the prognosis and immune infiltration of prostate cancer. P2RX2 expression was positively correlated with immune cell infiltration levels and the expression of immune checkpoint genes, and downregulation of P2RX2 led to poor survival in patients with prostate cancer. Furthermore, we validated the molecular and clinical characteristics of P2RX2 by using multiple databases and conducting in-vitro experiments. Additionally, drug sensitivity analysis revealed that patients with low P2RX2 expression were sensitive to docetaxel and Bicalutamide. In conclusion, we revealed an association between calcium channel-related genes and prostate cancer, and identified P2RX2 as a biomarker for early diagnosis, prognosis prediction, and aiding treatment decisions for patients with prostate cancer.

BackgroundExperimental biological research and clinical trials that relied on the healthcare system, access to public laboratory equipment, and adequate space were particularly affected by the COVID-19 pandemic and mobility restrictions. The study is to analyze the influence of COVID-19 on medical research by exploring the clinical trials and articles published by medical researchers worldwide during the COVID-19 pandemic.MethodsRoutinely conducted, deferred, and terminated clinical trial statistics from the Cancer Center of Tongji Hospital were collected during the COVID-19 pandemic. The number of global medical articles published in 2020 and those from the previous five years were analyzed according to the PubMed database. To conduct subgroup analyses, the articles were classified according to type and research field.Results The total number of publications per month in 2020 increased compared to the number of articles published in 2019. However, a decrease in the number of clinical trials was noted. Reviews and research papers increased by 7.28% and 20.60%, respectively. The number of clinical trial published decreased by 62.29%. The proportion of cancer-related publications (38.44% vs. 44.79%) decreased, whereas the proportion of immunology, pulmonology, and emergency publications (19.23% vs. 17.48%) increased. In the Cancer Center of the Tongji Hospital in Wuhan during the COVID-19 pandemic, of the 46 clinical trials analyzed, 37 (80.40%) were delayed, 8 (17.40%) were remote, and 1 (2.20%) was routine. Conclusions The COVID-19 pandemic had promoted the publication of medical research articles especially those related to the immunology, pulmonology, and emergency medicine. It had a pronounced negative impact on the execution and publication of clinical trials.

Tumor-associated macrophages have emerged as crucial factors for metastases. Microglia are indispensable components of the brain microenvironment and play vital roles in brain metastasis (BM). However, the underlying mechanism of how activated microglia promote brain metastasis of non-small cell lung cancer (NSCLC) remains elusive. Here, we purified cell lines with brain-metastatic tropism and employed a co-culture system to reveal their communication with microglia. By single-cell RNA-sequencing and transcriptome difference analysis, we identified IL6 as the key regulator in brain-metastatic cells (A549-F3) to induce anti-inflammatory microglia via JAK2/STAT3 signaling, which in turn promoted the colonization process in metastatic A549-F3 cells. In our clinical samples, patients with higher levels of IL6 in serum showed higher propensity for brain metastasis. Additionally, the TCGA (The Cancer Genome Atlas) data revealed that NSCLC patients with a lower level of IL6 had a longer overall survival time compared to those with a higher level of IL6. Overall, our data indicate that the targeting of IL6/JAK2/STAT3 signaling in activated microglia may be a promising new approach for inhibiting brain metastasis in NSCLC patients.

Radiation induced lung fibrosis (RILF) is a common late complication after radiotherapy without effective treatment. Thyroid hormone (TH) is known to reverse bleomycin-induced pulmonary fibrosis in recent study. We therefore sought to examine TH effect in RILF. Aerosolized TH delivery prevented pulmonary fibrosis according to either micro-computed tomography scans or histological evaluations, without significant changes in serum THs in a murine model of RILF by attenuating TGF-β1 and phosphorylated Smad2/3 expressions and reducing the accumulation of M2-like macrophages. Furthermore, hypothyroidism was significantly correlated with RILF in a retrospectively analyzed data from nasopharyngeal carcinoma patients treated by intensity-modulated radiation therapy with a median follow-up time of 25.5 months. Together, aerosolized TH may prevent RILF by inhibiting the TGF-β1/SMADs signaling pathway.

Background: Brain metastasis incidence in non-small cell lung cancer (NSCLC) patients is high; however, identifying patients that are most likely to develop brain metastases is difficult. The interleukin 6 (IL6)/interleukin 6 receptor (IL6R)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway contributes to lung cancer pathogenesis. Methods: We investigated whether the genetic variants of this pathway are useful for predicting brain metastases in non-small cell lung cancer (NSCLC). Thirty-eight single nucleotide polymorphisms (SNPs) in six core genes (IL6, IL6R, JAK1, JAK2, STAT1, and STAT3) were tested for potential associations with brain metastasis. Multivariate Cox regression analysis was used to analyse correlations between genotype variants and brain metastasis. Kaplan–Meier analysis was performed to evaluate cumulative hazard of brain metastasis. Bioinformatics tools were applied to assess the functional relevance of genetic variants. Findings: The GT/TT genotype of IL6R rs4845618 and the GA/AA genotype of JAK2 rs10815144 were associated with a higher risk of brain metastasis, after correcting for clinicopathologic variables (hazard ratio [HR], 7.888, 95% confidence interval [CI], 1.973–31.536, P = 0.003; HR, 4.378; 95% CI, 1.144–16.747; P = 0.031, respectively). These two SNPs had a cumulative effect on brain metastasis risk, and patients carrying both genotypes had a higher risk of brain metastasis. These two SNPs also affected the mRNA expression of genes. Interpretation: IL6R rs4845618 and JAK2 rs10815144 were associated with the risk of brain metastasis in NSCLC patients and may potentially be used as biomarkers of brain metastasis. Funding: This work was supported by the National Natural Science Foundation of China (Grant no. 81773360). Conflict of Interest: The authors declare no competing interests. Ethical Approval: The study was approved by the Ethics Committee of Tongji Medical College (IRBID: TJ-C20121219). All patients signed an informed consent form before the interview.

Radiation pneumonitis is a common complication of thoracic irradiation for lung cancer patients. The healthy gut microbiota plays an important role in the local mucosal defense process as well as pulmonary immunomodulation of the host. However, the effect of the intestinal microbiota on radiation pneumonitis is not well understood. Here we studied how the intestinal microbiota affected the host response to radiation pneumonitis. C57BL/6 mice were administered antibiotics to induce disequilibrium in the gut microbiota, and subsequently irradiated. We found that the intestinal microbiota served as a protective mediator against radiation pneumonitis, as indicated by decreased body weight and increased mortality in antibiotic-treated mice. In mice with gut microbiota disequilibrium, more serious pathological lung damage was observed at two and four weeks postirradiation. Fecal microbiota transplantation into irradiated mice led to improvement from radiation-induced inflammation two weeks postirradiation. High-throughput sequencing of murine feces displayed conversion of flora diversity, bacterial composition and community structure in the absence of normal intestinal flora. We filtered the potentially important species among the gut microbiota and considered that the tissue-type plasminogen activator might be involved in the inflammatory process. This study reveals that the gut microbiota functions as a protective regulator against radiation pneumonitis. Additionally, fecal microbiota transplantation was shown to alleviate lung injury in the irradiated model. The protective role of the healthy gut microbiota and the utilization of the gut-lung axis show potential for innovative therapeutic strategies in radiation-induced lung injury.

Radiation-induced complications of the respiratory system are a common side effect of thoracic radiotherapy with no viable treatment option. Here, we investigated the potential therapeutic effect of the orphan drug pirfenidone for treating radiation-induced pulmonary fibrosis. C57BL/6 mice received a single fraction of 16 Gy to the thorax and were subsequently treated with 300 mg/kg/day pirfenidone for four weeks. Survival and body weight of the mice were quantified. Micro-CT in vivo lung imaging was performed to dynamically observe the developmental process of pulmonary fibrosis. The lungs were excised at the end of the experiment and evaluated for histological changes. Compared to the irradiated mice that received no pirfenidone, mice treated with pirfenidone after irradiation had an extended median survival time (>140 days vs. 73 days, P < 0.01). The accumulation of collagen and fibrosis in lung tissues after irradiation was decreased with pirfenidone treatment. Pirfenidone also reduced the expression of TGF-β1 and phosphorylation of Smad3 in lung tissues. The dose level of Pirfenidone used in this study attenuated pulmonary fibrosis and prolonged the life span of irradiated mice. It may offer a promising approach to treat or minimize radiation-induced pulmonary fibrosis.