Genetic heterogeneity of tumor is closely related to its clonal evolution, phenotypic diversity and treatment resistance, and such heterogeneity has only been characterized at single-cell sub-chromosomal scale in liver cancer. Here we reconstructed the single-variant resolution clonal evolution in human liver cancer based on single-cell mutational profiles. The results indicated that key genetic events occurred early during tumorigenesis, and an early metastasis followed by independent evolution was observed in primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. By parallel single-cell RNA-Seq, the transcriptomic phenotype of HCC was found to be related with genetic heterogeneity. For the first time we reconstructed the single-cell and single-variant clonal evolution in human liver cancer, and dissection of both genetic and phenotypic heterogeneity will facilitate better understanding of their relationship.

Background: The 2019 novel coronavirus has continuous outbreaks around the world. Lung is the main organ that be involved. There is a lack of clinical data on the respiratory sounds of COVID-19 infected pneumonia, which includes invaluable information concerning physiology and pathology. The medical resources are insufficient, which are now mainly supplied for the severe patients. The development of a convenient and effective screening method for mild or asymptomatic suspicious patients is highly demanded. Methods: This is a retrospective case series study. 10 patients with positive results of nucleic acid were enrolled in this study. Lung auscultation was performed by the same physician on admission using a hand-held portable electronic stethoscope delivered in real time via Bluetooth. The recorded audio was exported, and was analyzed by six physicians. Each physician individually described the abnormal breathing sounds that he heard. The results were analyzed in combination with clinical data. Signal analysis was used to quantitatively describe the most common abnormal respiratory sounds. Results: All patients were found abnormal breath sounds at least by 3 physicians, and one patient by all physicians. Cackles, asymmetrical vocal resonance and indistinguishable murmurs are the most common abnormal breath sounds. One asymptomatic patient was found vocal resonance, and the result was correspondence with radiographic computed tomography. Signal analysis verified the credibility of the above abnormal breath sounds. Conclusions: This study describes respiratory sounds of patients with COVID-19, which fills up for the lack of clinical data and provides a simple screening method for suspected patients.

Hypertension has been recognized as one of the highest risk factors for cardiovascular diseases. Anti-hypertension agent screening and development has been recognized as a pharmaceutical therapy approach for the cardiovascular diseases treatment. Many kinds of traditional Chinese medicines, such as pine needle, have been used for the treatment of hypertension for a long time, but the bioactive ingredients which responsible for their therapeutic effectiveness are remain unclear. Therefore, screening bioactive chemicals in natural sources is still the most straightforward strategy for novel Angiotensin-converting enzyme inhibitor (ACEi)-based anti-hypertension agents discovery. In this study, we demonstrated a bioactivity-guided fractionation strategy for identifying bioactive fractions and chemicals from pine needle based on LC/MS assay as well as elucidating their mechanisms of pharmacological activity. And we found out the compound in pine needle extracts being ACE-inhibitory active is catechin. When ACE activity was assayed in rat tissue membranes, it was observed that catechin demonstrate ACE inhibition in kidney, lung and testes tissue. All these presents catechin in pine needle could be a potential cardiovascular medicine.