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To investigate the characteristics of rhizosphere soil microbial communities associated with Schisandra sphenanthera across different altitudinal gradients and to reveal the driving factors of microbial community dynamics, this study collected rhizosphere soil samples at four elevations: 900 m (HB1), 1100 m (HB2), 1300 m (HB3), and 1500 m (HB4). High-throughput sequencing and molecular ecological network analysis were employed to analyze the microbial community composition and species interactions. A null model was applied to elucidate community assembly mechanisms. The results demonstrated that bacterial communities were dominated by Proteobacteria, Acidobacteriota, Actinobacteriota, and Chloroflexi. The relative abundance of Proteobacteria increased with elevation, while that of Acidobacteriota and Actinobacteriota declined. Fungal communities were primarily composed of Ascomycota and Basidiomycota, with both showing elevated relative abundances at higher altitudes. Diversity indices revealed that HB2 exhibited the highest bacterial Chao, Ace, and Shannon indices but the lowest Simpson index. For fungi, HB3 displayed the highest Chao and Ace indices, whereas HB4 showed the highest Shannon index and the lowest Simpson index. Ecological network analysis indicated stronger bacterial competition at lower elevations and enhanced cooperation at higher elevations, contrasting with fungal communities that exhibited increased competition at higher altitudes. Altitude and soil nutrients were negatively correlated with soil carbon content, while plant nutrients and fungal diversity positively correlated with soil carbon. Null model analysis suggested that deterministic processes dominated bacterial community assembly, whereas stochastic processes governed fungal assembly. These findings highlight significant altitudinal shifts in the microbial community structure and assembly mechanisms in S. sphenanthera rhizosphere soils, driven by the synergistic effects of soil nutrients, plant growth, and fungal diversity. This study provides critical insights into microbial ecology and carbon cycling in alpine ecosystems, offering a scientific basis for ecosystem management and conservation.

Overall survival (OS) in patients with advanced or metastatic urothelial carcinoma (UC) is not optimistic. For a long time, the standard platinum-based chemotherapy has been one of the preferred treatment strategies. Despite the high initial objective response rate (ORR) to first-line chemotherapy in patients with metastatic UC, the rate of achieving complete response (CR) is low, and most patients will relapse within one year after first-line treatment. To further improve the OS of patients with metastatic UC, the success of the CheckMate901 and EV302 studies has brought new therapeutic options for the first-line treatment of these patients. Maintenance or consolidation therapy after first-line treatment is also important to improve the OS of patients with advanced UC. Maintenance therapy after first-line treatment of metastatic UC has undergone a long period of development until the success of the JAVELIN Bladder100 study. For the first time, this study established the application of avelumab as maintenance therapy after first-line platinum-containing chemotherapy. The aim of this paper is to review the development process of avelumab-based maintenance therapy after first-line treatment of advanced or metastatic UC and explore future options for maintenance therapy in patients with advanced or metastatic UC in the light of new first-line treatment options.

Urothelial carcinoma (UC) represents the most common pathological type of bladder cancer. For patients with locally advanced or metastatic UC (la/m UC), the standard of care with platinum-based chemotherapy as the cornerstone has greatly improved the survival time. Although the platinum-containing regimens have been established as the first-line therapeutic approach for la/m UC and demonstrate high initial response rates, most patients experience disease recurrence or metastasis shortly after treatment cessation, compounded by the inherent toxicity associated with platinum agents, which collectively pose substantial challenges to long-term patient survival. Moreover, some patients are ineligible to receive a platinum containing therapy, which greatly affects their potential possible benefit. With the success of the EV-302 study, the combination of enfortumab-vedotin (EV) and pembrolizumab has supplanted chemotherapy as the current standard of care for the first-line treatment of la/m UC, thus initiating a treatment paradigm of platinum-free for the first-line treatment of la/m UC. In recent years, the treatment landscape of la/m UC has witnessed remarkable shifts, evolving from traditional chemotherapy to the emerging “chemotherapy-free (platinum-free)” strategy. This article provides a comprehensive review of the historical development and outlook of first-line treatment strategies for la/m UC, including the role of chemotherapy, the rise of platinum-free and its clinical applications. Through this in - depth exploration, the article endeavors to offer readers a holistic understanding of the present treatment panorama for la/m UC, furnishing them with profound insights into the transformative trajectory and emerging trends within la/m UC treatment strategies.

Immune checkpoint inhibitor-associated myocarditis (ICI-M) is a rare yet potentially fatal complication of immunotherapy, with no standardized treatment protocol due to limited data. The use of varying steroid doses has resulted in inconsistent outcomes. We retrospectively identified patients diagnosed with ICI-M at our institution between January 2020 and February 2024. Additionally, we conducted a comprehensive literature review using PubMed, Embase, and the Cochrane Library to facilitate a comparative analysis of clinical responses. The primary aim was to compare clinical outcomes and therapeutic responses between patients treated with high-dose versus low-dose methylprednisolone. Patients receiving an initial high-dose intravenous methylprednisolone (1 g/day) exhibited a more rapid reduction in myocardial injury markers, including troponin I/T (cTnI/T), creatine kinase (CK), and N-terminal pro b-type natriuretic peptide (NT-proBNP), compared to those receiving lower doses. This group also demonstrated lower incidences of biomarker rebound and maintained lower levels over time. Additionally, the clinical treatment process was more straightforward in the high-dose group, with treatment efficacy surpassing that observed in patients who received an initial methylprednisolone (mPSL) dose of less than 1 g/day. Regarding prognosis, the incidence of major adverse cardiovascular events (MACE) and cardiovascular mortality was significantly lower in the high-dose group compared to the low-dose group. In patients with immune checkpoint inhibitor-associated myocarditis, the prompt administration of high-dose corticosteroid pulse therapy (1 g/day) is strongly associated with improved clinical outcomes. This intervention rapidly lowers myocardial injury biomarkers (cTnI/T, CK, NT-proBNP) while minimizing the risk of biomarker rebound, thus optimizing clinical management. Notably, it significantly reduces the incidence of major adverse cardiovascular events (MACE), thereby enhancing patient prognosis. The duration of therapy should be tailored based on clinical response. In cases of steroid resistance, combination therapies may provide additional benefit.

Purpose: A phase I/II study of intrathecal pemetrexed (IP) combined with involved-field radiotherapy (IFRT) was performed to determine feasibility, safety, and antitumor activity for leptomeningeal metastases (LM) from solid tumors. Methods: Participants first received induction IP administration, followed by concomitant radiotherapy within 3 days. The concomitant regimen consisted of IP (pemetrexed 10 mg, dexamethasone 5 mg, once per week, 4 times in 4 weeks) and IFRT (40 Gy in 20 fractions). Six participants were recruited to assess feasibility in phase I, and then 28 patients were recruited further. All patients were assessed to investigate safety, efficacy, and outcomes. Results: Between April 2018 and December 2018, 34 patients (male: 15; female: 19; median age: 56 years) were enrolled, including non-small-cell lung cancer (21), small-cell lung cancer (5), breast cancer (4), and others (4). Thirty-two patients received concurrent therapy and 25 (74%) patients completed the treatment. Major adverse events (AEs) consisted of myelosuppression, the elevation of hepatic aminotransferases, and radiculitis. Total AEs rate was 53% (18/34), including 6 (18%) patients with grade 3 and 1 (3%) with grade 4 AEs. The response rate was 68% (23/34). The median overall survival was 5.5 (0.3–16.6) months. Median neurological progression-free survival (NPFS) was 3.5 (0.3–15.2) months. Six-month NPFS rate was 47%. One-year survival rate was 21.6%. Conclusion: IP at a 10 mg dose on a schedule of 1–2 times per week presented good efficacy and safety in CSF. The concomitant regimen is an efficacious therapeutic option for LM patients with solid tumors. Trial Registration: This study (IPLM) was registered at https://register.clinicaltrials.gov [ClinicalTrials.gov identifier: NCT03507244].

This pilot study (NCT03958097; https://www.clinicaltrials.gov/ct2/show/NCT03958097 ) was aimed to evaluate the efficacy and safety of PD-1 antibody combined autologous NK cells in the treatment of patients with stage IIIB/IIIC or IV non-small-cell lung cancer (NSCLC) who failed the first-line platinum-based chemotherapy. All patients received both sintilimab 200mg and 3×10 9 NK cells every 3 weeks. 20 patients were enrolled, median follow up time was 22.6 months. The median PFS was 11.6 months, ORR was 45%. Median OS was 17.7 months, 6-month OS rate and 12-month OS rate was 95.0% and 80.0%. Unexpected adverse events were not observed. 2 patients reported grade 3 adverse events (hypertriglyceridemia, neutropenia and increased creatine kinase). The autologous NK cells did not add extra adverse events to the ICI treatment. Autologous NK plus sintilimab showed promising antitumor activity and an acceptable safety profile in advanced driven-mutation negative NSCLC who failed on the first line treatment.

Combination strategies involving immune checkpoint inhibitors (ICIs) have been a prominent focus of research in the treatment of non-small cell lung cancer (NSCLC). Our prior findings demonstrated that the combination of autologous NK cells with the PD-1 antibody (Sintilimab), offered promising efficacy in NSCLC patients who failed the first-line platinum-based chemotherapy. Here, we present updated overall survival (OS) data from the final analysis, aiming to identify patient subgroups that derive maximal benefit from this therapeutic approach. Twenty NSCLC patients without driver gene mutations were enrolled and treated with a combination of autologous NK cells and Sintilimab every three weeks. Multicolor immunofluorescence staining was applied to evaluate static markers within the tumor microenvironment. Concurrently, dynamic assessments were conducted using next-generation sequencing and monitoring of PD-1/PD-L1 expression on NK cells to identify patient populations with favorable prognoses. The median OS was 27.3 months (95% CI, 0.76 to 53.8), with six patients still alive at the follow-up cutoff. A significant correlation was observed between the CD56+PD-L1+ cellular phenotype and extended survival. Clearance of circulating tumor DNA (ctDNA) and an increased percentage of PD-L1+ NK cells following treatment was associated with significantly better survival outcomes. Notably, prolonged treatment exposure did not lead to increased toxicity. The combination of autologous NK cells with Sintilimab significantly enhances long-term survival in NSCLC patients without exacerbating adverse effects, presenting a promising strategy for future combination immunotherapy approaches in NSCLC treatment. https://www.clinicaltrials.gov/ct2/show/NCT03958097, identifier NCT03958097.

Chronic myeloid leukemia (CML) is a hematopoietic malignancy characterized by dysregulated growth and proliferation of hematopoietic stem/progenitor cells in bone marrow and excessive expansion of hematopoietic compartments in peripheral blood. Expression deletion of Hiwi, a human Piwi homolog, has been reported to be implicated in leukemogenesis. We here explored Hiwi’s role in CML pathogenesis by determining how and whether its forced overexpression could affect CML cell growth and migration. The present results showed that lentivirus-mediated overexpression of Hiwi significantly suppressed cell proliferation and induced obvious apoptosis in K562 cells, a CML line cell line. Tumors in BALB/c nude mice generated by the K562 cells expressing Hiwi were much smaller than those formed by the control cells. Like in vitro, Hiwi upregulation induced cell apoptosis in the tumor tissues in vivo. Additionally, Hiwi elevation suppressed K562 cell migration and inhibited the activity and expression of matrix metalloproteinase-2 and -9. In summary, our study demonstrates that Hiwi overexpression inhibits CML cell growth and migration, providing insights into its role in CML pathogenesis.

Background. Genomic testing gives guidance to the treatment options in lung adenocarcinoma patients, but some patients are unable to obtain tissue samples due to lesion location or intolerance. Cell-free circulating tumor DNA (ctDNA) tested in plasma or pleural effusion is an advanced access to solve the problem. Our study descriptively identified the genetic variations of advanced Chinese lung adenocarcinoma patients and analyzed the overall survival of patients with EGFR mutations. Methods. A total of 152 patients’ plasma samples were included, and gene mutations were detected by NGS using an Illumina Miseq tabletop sequencer. Results. Frequencies of altered were EGFR 46.05%, ALK 7.24%, KRAS 6.58%, PIK3CA 6.58%, PTEN 2.63%, HER2 1.97%, MET 1.97%, BRAF 1.32%, NF1 1.32%, and ROS1 0.66%. We identified 48 cases with double or triple driver gene mutations. Multiple mutations were more frequently observed in EGFR and PIK3CA genes. Patients harboring coexistent mutations with an EGFR mutation tended to have a shorter overall survival than those with exclusively EGFR mutations. Conclusion. EGFR, ALK, and KRAS were common driver gene in Chinese patients with stage IV lung adenocarcinoma. Multiple mutations were detected in the ctDNA samples and involve more EGFR and PIK3CA mutations. The existence of coexisting gene mutations may have adverse effects on the prognosis of patients with EGFR mutation. The unknown mutations discovered by NGS may provide new targets for gene targeting therapy, and ctDNA test by NGS is an effective method for making appropriate treatment choices.

This study aimed to explore the association between mental health knowledge level and the prevalence of depressive symptoms among Chinese college students. A cross-sectional study was conducted in six universities in Jinan, Shandong Province, China, and a total of 600 college students were recruited to self-complete a series of questionnaires. The Mental Health Knowledge Questionnaire (MHKQ) was used to investigate the level of mental health knowledge. Depressive symptoms were investigated with the depression subscale of the Depression Anxiety Stress Scale (DASS-21). The prevalence rate of depressive symptoms among college students was 31.2%. Compared with MHKQ scoring in the 1st quartile, college students with MHKQ scoring in the 3rd quartile and in the 4th quartile reported lower levels of depressive symptoms after adjusting for potential confounding factors. Since mental health knowledge level was related to depressive symptoms among college students, increased efforts to promote the level of mental health knowledge in Chinese college students are critical.