Perineural invasion in colorectal cancer: mechanisms of action and clinical relevance.

BACKGROUND: In recent years, the significance of the nervous system in the tumor microenvironment has gained increasing attention. The bidirectional communication between nerves and cancer cells plays a critical role in tumor initiation and progression. Perineural invasion (PNI) occurs when tumor cells invade the nerve sheath and/or encircle more than 33% of the nerve circumference. PNI is a common feature in various malignancies and is associated with tumor invasion, metastasis, cancer-related pain, and unfavorable clinical outcomes. The colon and rectum are highly innervated organs, and accumulating studies support PNI as a histopathologic feature of colorectal cancer (CRC). Therefore, it is essential to investigate the role of nerves in CRC and comprehend the mechanisms of PNI to impede tumor progression and improve patient survival. CONCLUSION: This review elucidates the clinical significance of PNI, summarizes the underlying cellular and molecular mechanisms, introduces various experimental models suitable for studying PNI, and discusses the therapeutic potential of targeting this phenomenon. By delving into the intricate interactions between nerves and tumor cells, we hope this review can provide valuable insights for the future development of CRC treatments.

Revealing Inter-regional Environmental Inequities Hidden in China's Energy Transition.

Energy transition is an important way to control air pollution, but it may conflict with the economic goal of alleviating regional inequality due to its inherently different cost burdens. As one of the effective measures of energy transition, this paper takes small coal-fired boiler (SCB) upgrading as an example to explore the regional mismatch between upgrading costs and health benefits. Here, we construct a boiler-level inventory of SCB upgrades for the North China Plain (NCP) during 2013-2017 and propose an integrated modeling framework to quantify the spatial contribution of economic costs and health benefits associated with SCB upgrading. We find that although the total health benefits could offset the total costs for the entire region, the developed municipalities (Beijing and Tianjin) are likely to gain more health benefits from less-developed neighboring provinces at lower costs. These developed municipalities contribute only 14% to the total health benefits but gain 21% of the benefits within their territories, 56% of which come from neighboring provinces. Their benefits are approximately 5.6 times their costs, which is much higher than the 1.5 benefit-cost ratio in neighboring provinces. Our findings may be useful in shaping more equitable and sound environmental policies in China or other regions of the world with serious coal-related air pollution.

Gut mucosal microbiota profiles linked to colorectal cancer recurrence.

BACKGROUND: Emerging evidence links gut microbiota to various human diseases including colorectal cancer (CRC) initiation and development. However, gut microbiota profiles associated with CRC recurrence and patient prognosis are not completely understood yet, especially in a Chinese cohort. AIM: To investigate the relationship between gut mucosal microbiota profiles and CRC recurrence and patient prognosis. METHODS: We obtained the composition and structure of gut microbiota collected from 75 patients diagnosed with CRC and 26 healthy controls. The patients were followed up by regular examination to determine whether tumors recurred. Triplet-paired samples from on-tumor, adjacent-tumor and off-tumor sites of patients diagnosed with/without CRC recurrence were analyzed to assess spatial-specific patterns of gut mucosal microbiota by 16S ribosomal RNA sequencing. Next, we carried out bioinformatic analyses, Kaplan-Meier survival analyses and Cox regression analyses to determine the relationship between gut mucosal microbiota profiles and CRC recurrence and patient prognosis. RESULTS: We observed spatial-specific patterns of gut mucosal microbiota profiles linked to CRC recurrence and patient prognosis. A total of 17 bacterial genera/families were identified as potential biomarkers for CRC recurrence and patient prognosis, including Anaerotruncus, Bacteroidales, Coriobacteriaceae, Dialister, Eubacterium, Fusobacterium, Filifactor, Gemella, Haemophilus, Mogibacteriazeae, Pyramidobacter, Parvimonas, Porphyromonadaceae, Slackia, Schwartzia, TG5 and Treponema. CONCLUSION: Our work suggests that intestinal microbiota can serve as biomarkers to predict the risk of CRC recurrence and patient death.

Concurrent chemoradiotherapy using gemcitabine and nedaplatin in recurrent or locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Patients with recurrent or locally advanced head and neck squamous cell carcinoma (HNSCC) typically have limited treatment options and poor prognosis. AIM: To evaluate the efficacy and safety of two drugs with potent radio-sensitization properties including gemcitabine and nedaplatin as concurrent chemoradiotherapy regimens in treating HNSCC. METHODS: This single-arm prospective study enrolled patients with HNSCC to receive gemcitabine on days 1 and 8 and nedaplatin on days 1 to 3 for 21 days. Intensity-modulated radiation therapy with a conventional fraction was delivered 5 days per week. Objective response rate (ORR), disease control rate, and toxicity were observed as primary endpoints. Overall survival (OS) and progression free survival were recorded and analyzed as secondary endpoints. RESULTS: A total of 24 patients with HNSCC were enrolled. During the median 22.4-mo follow-up, both ORR and disease control rate were 100%. The one-year OS was 75%, and one-year progression-free survival (PFS) was 66.7% (median PFS was 15.1 mo). Recurrent HNSCC patients had a poorer prognosis than the treatment-naïve patients, and patients who achieved complete response had better survival than those in the PR group (all P < 0.05). The most common grade 1-4 (100%) or grade 3-4 toxicities (75%) were hematological, and the most common grade 3-4 non-hematological toxicity was mucositis in 17 (71%) patients. CONCLUSION: Gemcitabine plus nedaplatin with concurrent chemoradiotherapy is a therapeutic option for HNSCC with predictable tolerability. Considering the high adverse event rate, the optimized dose and schedule must be further explored.