A single-cell atlas of liver metastases of colorectal cancer reveals reprogramming of the tumor microenvironment in response to preoperative chemotherapy.

Metastasis is the primary cause of cancer-related mortality in colorectal cancer (CRC) patients. How to improve therapeutic options for patients with metastatic CRC is the core question for CRC treatment. However, the complexity and diversity of stromal context of the tumor microenvironment (TME) in liver metastases of CRC have not been fully understood, and the influence of stromal cells on response to chemotherapy is unclear. Here we performed an in-depth analysis of the transcriptional landscape of primary CRC, matched liver metastases and blood at single-cell resolution, and a systematic examination of transcriptional changes and phenotypic alterations of the TME in response to preoperative chemotherapy (PC). Based on 111,292 single-cell transcriptomes, our study reveals that TME of treatment-naïve tumors is characterized by the higher abundance of less-activated B cells and higher heterogeneity of tumor-associated macrophages (TAMs). By contrast, in tumors treated with PC, we found activation of B cells, lower diversity of TAMs with immature and less activated phenotype, lower abundance of both dysfunctional T cells and ECM-remodeling cancer-associated fibroblasts, and an accumulation of myofibroblasts. Our study provides a foundation for future investigation of the cellular mechanisms underlying liver metastasis of CRC and its response to PC, and opens up new possibilities for the development of therapeutic strategies for CRC.

Hypothermia alleviated LPS-induced acute lung injury in Rat models through TLR2/MyD88 pathway.

Acute lung injury (ALI) is a common clinical syndrome in ICU departments with high mortality. The pathology of ALI is still not clear and there is no specific and efficient treatment against ALI. In this study, we established ALI rat model through lipopolysaccharide administration. We found that hypothermia therapy led to significant improvement in oxygenation index, edema formation and pathological score, demonstrating that hypothermia is beneficial to the recovery of lung function and alleviation of lung injury. Besides, hypothermia resulted in a decrease in plasminogen activator inhibitor-1(PAI-1) concentration, showing the inflammation was partially inhibited. This was also confirmed by a decrease in TNF-α mRNA and protein level in hypothermia group. The effect of hypothermia was mediated by TLR2/MyD88 signaling, which led to the alteration in NF-κB p65 level. Collectively, this study indicated that hypothermia therapy was potentially an efficient therapy against ALI.

Macrolactins from Marine-Derived Bacillus subtilis B5 Bacteria as Inhibitors of Inducible Nitric Oxide and Cytokines Expression.

In order to find new natural products with anti-inflammatory activity, chemical investigation of a 3000-meter deep-sea sediment derived bacteria Bacillus subtilis B5 was carried out. A new macrolactin derivative was isolated and identified as 7,13-epoxyl-macrolactin A (1). Owing to the existence of the epoxy ring, 1 exhibited a significant inhibitory effect on the expression of inducible nitric oxide and cytokines, compared with previously isolated known macrolactins (2-5). Real-time Polymerase Chain Reaction (PCR) analysis showed that the new compound significantly inhibited the mRNA expressions of inducible nitric oxide synthase (iNOS), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Reverse transcription-PCR analysis demonstrated that the new compound reduced the mRNA expression level of IL-1ß in a concentration-dependent manner.

[Clinical features and epidemiological trend of diabetic ketosis in patients admitted to West China Hospital].

OBJECTIVE: To evaluate the clinical features and epidemiological trend of diabetes ketosis (DK) in patients admitted to West China Hospital. METHODS: We reviewed medical records of diabetic patients with DK who were admitted to West China Hospital from 1997 to 2005. Their clinical and laboratory data were analysed with SAS 9.0. RESULTS: From 1997 to 2005, the proportion of diabetic patients with DK increased by 0.12% annually. The proportion of provoked DK patients (who had a clinically evident precipitating factor) in those with DK remained stable; whereas the proportion of T1D patients in those with DK declined by 2.00% annually and the proportion of ketosis prone obesity diabetes (KPD) in those with DK increased by 2.27% annually. The KPD patients displayed a striking male predominance (2.31:1, male:female) and were diagnosed at an older age compared with those with T1D [(46.3 +/- 12.9) yr. vs. (28.9 +/- 14.7) yr.]. The KPD patients were more likely to have a strong family history of diabetes and a better beta-cell function reserve, and be accompanied with dyslipidemia (52.7%), hypertension (23.3%), fatty liver (10.1%) and hyperuricemia/gout (8. 5%) compared with those with T1D. CONCLUSION: In recent years the proportion of KPD patients in the hospitalized DK patients is increasing. With different characteristics compared with typical T1D, KPD might belong to a subgroup of T2D.