PD-1/PD-L1 Inhibitor Plus Chemotherapy Versus PD-1/PD-L1 Inhibitor in Microsatellite Instability Gastrointestinal Cancers: A Multicenter Retrospective Study.

PURPOSE: To investigate the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy versus anti-PD-1/PD-L1 monotherapy in advanced microsatellite instability (MSI)/mismatch repair-deficient (dMMR) gastrointestinal cancers. METHODS: We retrospectively recruited patients with MSI/dMMR gastrointestinal cancer who received anti-PD-1/PD-L1 with or without chemotherapy and compared objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of PD-1/PD-L1 inhibitor plus chemotherapy (chemo-anti-PD-1/PD-L1 group) and PD-1/PD-L1 inhibitor alone (anti-PD-1/PD-L1 group). Propensity score-based overlap weighting analysis was conducted to adjust the baseline covariable imbalance. Sensitivity analysis was performed to confirm the stability of the results by propensity score matching and multivariable Cox and logistic regression models. RESULTS: A total of 256 patients were eligible, with 68 and 188 receiving chemo-anti-PD-1/PD-L1 and anti-PD-1/PD-L1, respectively. The chemo-anti-PD-1/PD-L1 group showed significant improvements versus the anti-PD-1/PD-L1 group in ORR (61.8% v 38.8%; P = .001), DCR (92.6% v 74.5%; P = .002), PFS (median PFS [mPFS], not reached [NR] v 27.9 months; P = .004), and OS (median OS [mOS], NR v NR; P = .014). After overlap weighting, the improvements tended to be more significant with chemo-anti-PD-1/PD-L1 versus anti-PD-1/PD-L1 in ORR (62.5% v. 38.3%; P < .001), DCR (93.8% v 74.2%; P < .001), PFS (mPFS, NR v 26.0 months; P = .004), and OS (mOS, NR v NR; P = .010). These results were solidified through sensitivity analysis. CONCLUSION: Chemo-anti-PD-1/PD-L1 is superior to anti-PD-1/PD-L1 in MSI/dMMR gastrointestinal cancers with improved efficacy.

Secondary coronary artery ostial lesions: Three case reports.

BACKGROUND: Atherosclerosis is one of the main causes of coronary artery ostial lesions seen clinically. Secondary coronary artery ostial lesions are rare, and cases reported previously were associated with syphilitic vasculitis and aortic dissection. Here, we report three rare cases of secondary coronary ostial lesions. Due to their rareness, these lesions can easily be neglected, which may lead to misdiagnosis and missed diagnosis. CASE SUMMARY: We present three patients with acute myocardial infarction and unstable angina caused by secondary coronary artery ostial lesions. In Case 1, coronary angiography (CAG) revealed 90% stenosis of the left main coronary ostium. Chest contrast computed tomography (CT) suggested thymic carcinoma invading the left main coronary ostium. Coronary artery bypass grafting and tumor resection were performed. In Case 2, echocardiography revealed a sinus of Valsalva aneurysm (SVA)-like dilatation. CAG showed a right coronary sinus giant aneurysm and complete obstruction of the right coronary artery (RCA) ostium. Aortic contrast CT confirmed these findings. The Bentall procedure was performed. In Case 3, CT CAG identified an anomalous origin of the right coronary artery (AORCA) from the left sinus of Valsalva coursing between the aorta and pulmonary trunk, causing severe RCA ostium stenosis by compression. Surgical correction of the AORCA was performed. CONCLUSION: The cases reported here suggest that we should consider other causes of coronary ostial lesions other than atherosclerosis.

Mechanisms of anti-inflammation of taurochenodeoxycholic acid based on network pharmacology / 药学学报

To investigate the anti-inflammatory mechanisms of taurochenodeoxycholic acid (TCDCA), the molecule structure file of TCDCA was downloaded from PubChem database, PharmMapper and GeneCards were used to predict and screen the targets of TCDCA. STRING database and Cytoscape software were used to construct protein interactions network. GO and KEGG analysis was preformed through STRING database. The key targets were validated by molecular docking and the targets type was attributed by DisGeNET database. The network showed that 89 targets were involved in 68 biological processes including response to stimulus, multicellular organismal process, single-multicellular organism process, response to chemical, response to organic substance, by adjusting 51 signaling pathways, such as pathways in cancer, progesterone-mediated oocyte maturation, MAPK signaling pathway, proteoglycans in cancer. These findings provide an overview of anti-inflammation of TCDCA, which reflects the characteristic of multi-targets and multi-pathways of TCDCA. It pointed out the direction for further research on anti-inflammatory mechanism of TCDCA.

[Effect of juglone on the ultrastructure of human liver cancer BEL-7402 cells].

OBJECTIVE: To study the effect of juglone on the ultrastructure of human liver cancer BEL-7402 cells. METHODS: BEL-7402 cells were incubated in the presence of 12.5 micromol/L juglone for 24 h, and fixed in 2.5% glutaraldehyde for HE staining and Coomassie brilliant blue staining and scanning electron microscopy. RESULTS: Incubation with juglone resulted in obvious changes in the cell morphology and cytoskeletal alterations of the cells. Scanning electron microscopy revealed reduced volume of the cell bodies, dissociation of the cells, curling and malformation of the microvilli on the cell surface with rupture of the intercellular junction and enlargement of the intercellular space. The formation of apoptotic bodies was observed. Transmission electron microscopy showed expansion of the endoplasmic reticula, mitochondrial cristea disintegration, nucleolar fragmentation and formation of the apoptotic bodies after the exposure to juglone for 24 h. CONCLUSION: Juglone can cause ultrastructural changes of human liver cancer BEL-7402 cells and induce their apoptosis.

Effect of juglone on the ultrastructure of human liver cancer BEL-7402 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of juglone on the ultrastructure of human liver cancer BEL-7402 cells.</p><p><b>METHODS</b>BEL-7402 cells were incubated in the presence of 12.5 micromol/L juglone for 24 h, and fixed in 2.5% glutaraldehyde for HE staining and Coomassie brilliant blue staining and scanning electron microscopy.</p><p><b>RESULTS</b>Incubation with juglone resulted in obvious changes in the cell morphology and cytoskeletal alterations of the cells. Scanning electron microscopy revealed reduced volume of the cell bodies, dissociation of the cells, curling and malformation of the microvilli on the cell surface with rupture of the intercellular junction and enlargement of the intercellular space. The formation of apoptotic bodies was observed. Transmission electron microscopy showed expansion of the endoplasmic reticula, mitochondrial cristea disintegration, nucleolar fragmentation and formation of the apoptotic bodies after the exposure to juglone for 24 h.</p><p><b>CONCLUSION</b>Juglone can cause ultrastructural changes of human liver cancer BEL-7402 cells and induce their apoptosis.</p>