Clinical and biomarker analyses of SHR-1701 combined with famitinib in patients with previously treated advanced biliary tract cancer or pancreatic ductal adenocarcinoma: a phase II trial.

Advanced biliary tract cancer (BTC) and pancreatic ductal adenocarcinoma (PDAC) have poor prognoses and limited treatment options. Here, we conducted this first-in-class phase II study to evaluate the efficacy and safety of SHR-1701, a bifunctional fusion protein targeting programmed death-ligand 1 (PD-L1) and transforming growth factor-beta (TGF-β), combined with famitinib, a multi-targeted receptor tyrosine kinase inhibitor, in patients with advanced BTC or PDAC who failed previous standard treatment (trial registration: ChiCTR2000037927). Among 51 enrolled patients, the BTC cohort showed an objective response rate (ORR) of 28% (including 2 complete responses) and a disease control rate (DCR) of 80%, with a median progression-free survival (mPFS) of 5.

Single cell and bulk RNA sequencing identifies tumor microenvironment subtypes and chemoresistance-related IGF1 cancer-associated fibroblast in gastric cancer.

Background: The tumor microenvironment (TME) significantly influences prognosis and drug resistance in various tumors, yet its heterogeneity and the mechanisms affecting therapeutic response remain unclear in gastric cancer (GC).

Methods: The heterogenous TME were explored with single-cell RNA-sequencing (scRNA-seq) data of 50 primary GC samples. We then identified four GC TME subtypes with nonnegative matrix factorization (NMF) and constructed a pearson nearest-centroid classifier based on subtype-specific upregulated genes.

Long-lasting complete response to SHR-1701 plus famitinib in refractory advanced gallbladder cancer: A case report.

Biliary tract cancer (BTC) is an aggressive malignancy with few options for advanced-stage treatment. The combination of PD-1/PD-L1 inhibitors with famitinib, a receptor tyrosine kinase (RTK) inhibitor, has demonstrated improved clinical outcomes in several clinical trials. We herein reported a case of a gallbladder cancer (GBC) patient with liver metastases, previously resistant to traditional chemotherapy.

[Spatial Distribution, Speciation, and Ecological Risk Assessment of Heavy Metals in Surface Sediments of Dongjiang Lake, Hunan Province].

To understand the heavy metal pollution status of Dongjiang Lake, the contents and species of heavy metals in the surface sediments were investigated during September 2021, and the heavy metal pollution level and potential ecological risk were evaluated. The results showed that Cd, Pb, As, Cu, Zn, Ni, and Cr contents were in the range of 0.40-34.

Use and misuse of random forest variable importance metrics in medicine: demonstrations through incident stroke prediction.

Background: Machine learning tools such as random forests provide important opportunities for modeling large, complex modern data generated in medicine. Unfortunately, when it comes to understanding why machine learning models are predictive, applied research continues to rely on 'out of bag' (OOB) variable importance metrics (VIMPs) that are known to have considerable shortcomings within the statistics community. After explaining the limitations of OOB VIMPs - including bias towards correlated features and limited interpretability - we describe a modern approach called 'knockoff VIMPs' and explain its advantages.

Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China.

Although the respiratory and immune systems are the major targets of Coronavirus Disease 2019 (COVID-19), acute kidney injury and proteinuria have also been observed. Currently, detailed pathologic examination of kidney damage in critically ill patients with COVID-19 has been lacking. To help define this we analyzed kidney abnormalities in 26 autopsies of patients with COVID-19 by light microscopy, ultrastructural observation and immunostaining.

Case report: lipid inclusion in glomerular endothelial and mesangial cells in a patient after contrast medium injection.

Background: It is well-recognized that injection of iodinated radiographic contrast media (CM) sometimes causes acute renal injury via multiple mechanisms, such as vasoconstriction, toxicity on glomerular endothelium and tubular epithelium and so forth.

Case Presentation: A 51-year-old man developed acute renal injury with proteinuria after CM administration. To our surprise, in his renal biopsy sample the myelin figure like structure was observed in glomerular endothelium and mesangial cells by transmission electron microscopy.