IntroductionCholangiocarcinoma (CCA) is a malignant tumor of the biliary epithelium with a poor prognosis. The lack of biomarkers to predict therapeutic response and prognosis is one of the major challenges for CCA treatment. Tertiary lymphoid structures (TLS) provide a local and pivotal microenvironment for tumor immune responses. The prognostic value and clinical relevance of TLS in CCA remain unclear. We aimed to explore the characteristics and clinical significance of TLS in CCA.MethodsWe investigated the prognostic value and clinical relevance of TLS in CCA using a surgery cohort containing 471 CCA patients (cohort 1) and an immunotherapy cohort containing 100 CCA patients (cohort 2). Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were used to evaluate the maturity of TLS. Multiplex IHC (mIHC) was employed to characterize the composition of TLS.ResultsDifferent maturity of TLS were observed in CCA tissue sections. Strong staining of the four-gene signature including PAX5, TCL1A, TNFRSF13C, and CD79A were found in TLS regions. A high density of intra-tumoral TLS (T-score high) were significantly correlated with longer overall survival (OS) both in CCA cohort 1 (p = 0.002) and cohort 2 (p = 0.01), whereas a high density of peri-tumoral TLS (P-score high) were associated with shorter OS in these two cohorts (p = 0.003 and p = 0.03, respectively).ConclusionThe established four-gene signature efficiently identified the TLS in CCA tissues. The abundance and spatial distribution of TLS were significantly correlated with the prognosis and immune checkpoint inhibitors (ICIs) immunotherapy response of CCA patients. The presence of intra-tumoral TLS are positive prognostic factors for CCA, which provide a theoretical basis for the future diagnosis and treatment of CCA.

Background : The coronavirus pandemic has become a growing public health concern worldwide, and there are insufficient epidemiological data on critical illness. Objective: To investigate the clinical course and features of critical patients with Corona Virus Disease 2019 ( COVID-19 ). Methods: The data on 94 consecutive critical patients from 8 th February through 16 th March 2020, including demographic and clinical information, were obtained from the intensive care unit (ICU) of Wuhan Huoshenshan Hospital. A cross-sectional survey and comparisons of key biomarkers between survivors and nonsurvivors were performed. Results: Over the study period, 42 nonsurvivors and 52 survivors were included. The overall case fatality rate for critical patients with COVID-19 was approximately 45%. The average age was 69.17±9.55 years, and the majority had underlying health problems such as hypertension (56[60%]) and diabetes (18[19%]). The median length of ICU stay was 8 days (IQR 4, 13). Compared with survivors, nonsurvivors were more likely to develop sepsis (42[100%] vs. 34[65%]), acute respiratory distress syndrome (40[95%] vs. 28[54%]) and organ dysfunction. In addition, the dynamic changes in some biomarkers were significantly different between the two groups. The trajectories of temperature revealed that the group with a high temperature on admission that steadily declined had the highest percentage of deaths (93.33%). Conclusions: Patients aged 60 years or older with many concomitant diseases were at highest risk, and the fatality rate started to increase with age. Lymphocyte, platelet, C-reactive protein and hypersensitivity troponin I were revealed to have potential as prognostic factors, whereas some other biomarkers, such as hepatic enzymes, may not offer additional information. Moreover, patients with high temperatures on admission should receive extra care.

Background and Aims: The coronavirus pandemic has become a growing public health concern worldwide, and there are insufficient epidemiological data on critical illness. We sought to investigate the clinical course and features of critical patients with Corona Virus Disease 2019 (COVID-19).Method: The data on 94 critical patients from 8th February through 16th March 2020, including demographic and clinical information, were obtained from the intensive care unit (ICU) of Wuhan Huoshenshan Hospital. A cross-sectional survey and comparisons of key biomarkers between survivors and nonsurvivors were performed.Results: Over the study period, 42 nonsurvivors and 52 survivors were included. The overall case fatality rate for critical patients with COVID-19 was approximately 45%. The average age was 69.17±9.55 years, and the majority had underlying health problems such as hypertension (56[60%]) and diabetes (18[19%]). The median length of ICU stay was 8 days (IQR 4, 13). Compared with survivors, nonsurvivors were more likely to develop sepsis (42[100%] vs. 34[65%]), acute respiratory distress syndrome (40[95%] vs. 28[54%]) and organ dysfunction. In addition, the dynamic changes in some biomarkers were significantly different between the two groups. The trajectories of temperature revealed that the group with a high temperature on admission that steadily declined had the highest percentage of deaths (93.33%).Conclusion: Patients aged 60 years or older with many concomitant diseases were at highest risk, and the fatality rate started to increase with age. Lymphocyte, platelet, C-reactive protein and hypersensitivity troponin I were revealed to have potential as prognostic factors, whereas some other biomarkers, such as hepatic enzymes, may not offer additional information. Moreover, patients with high temperatures on admission should receive extra care.

Tyrosine kinase inhibitors (TKIs)-based systemic therapy for advanced hepatocellular carcinoma (HCC) has only limited clinical benefit and reaches a bottleneck due to its drug resistance. Here, through whole transcriptome sequencing (RNA-Seq) and lipidomic analysis, we uncover that lipid metabolism reprogramming mediated by unconventional prefoldin RPB5 interactor (URI) endows HCC with resistance to TKIs-induced ferroptosis. Mechanistically, URI directly interacts with TRIM28 and promotes p53 ubiquitination and degradation in a TRIM28-MDM2 dependent manner. Importantly, we find that p53 binds to the promoter of stearoyl-CoA desaturase 1 (Scd1) and represses its transcription. Therefore, high expression of URI is correlated with high level of SCD1 and their synergetic expression predicts poor prognosis and TKIs resistance in HCC. The combination of SCD1 inhibitor aramchol and deuterated sorafenib derivative donafenib displays promising anti-tumor effects in xenografted models of wild-type p53 liver cancer cell lines. This combination therapy has potential significant clinical benefits for the patients with advanced HCC who have wild-type p53 and high levels of URI/SCD1.

Background: Nationally, the indicators tracking the coronavirus pandemic has remained stable. However, it’s still a public health concern and it’s worth providing more front-line data on critical illness. We aim to investigate the clinical course and features of critical patients with Corona Virus Disease 2019 (COVID-19).Methods: The data on 124 consecutive critical patients from 8th February through April 16th 2020, including demographic and clinical information, were obtained from the intensive care unit (ICU) of Wuhan Huoshenshan Hospital. A cross-sectional survey and comparisons of key biomarkers between survivors and nonsurvivors were performed.Results: Over the study period, 57 nonsurvivors and 67 survivors were included. The overall case-fatality rate for critical patients with COVID-19 was approximately 46%. The overall average age was 69.89±11.03 years, and the majority had underlying health problems such as hypertension (63[51%]) and diabetes (27[22%]). Compared with survivors, nonsurvivors were more likely to develop sepsis (57[100%] vs. 34[51%]), acute respiratory distress syndrome (52[91%] vs. 21[38%]) and organ dysfunction. Besides, the dynamic changes in some biomarkers (i.e. WBC, TLC, CRP, PLT) were significantly different between the two groups. The trajectories of temperature revealed that the group with a high temperature on admission that steadily declined had the highest percentage of deaths (84.21%).Conclusions: The elderly with many concomitant diseases were at the highest risk. Lymphocyte, platelet, C-reactive protein and temperature were revealed to have potential as prognostic factors, whereas some other biomarkers, such as hepatic enzymes, may not offer additional information. Moreover, patients with high temperatures on admission should receive extra care.