A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients

The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis and comparisons with healthy controls revealed extensive changes in the cellular composition and expression states in COVID-19 liver, reflecting hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis. We also observed Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas, resembling similar responses in liver injury in mice and in sepsis, respectively. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition was dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.

HBV infection may reduce the risk of metachronous liver metastasis in postoperative pathological stage 2 colorectal cancer.

PURPOSE: To analyze whether HBV infection can reduce the risk of colorectal liver metastasis (CRLM) in stage 2 colorectal cancer (CRC). METHODS: The data of postoperative pathological stage 2 CRC patients treated at the Sixth Affiliated Hospital of Sun Yat-sen University between 2013 and 2015 were analyzed. The patients were divided into an infection group (group A) and a non-infection group (group B). The correlations between HBV infection and CRLM, 5-year liver disease-free survival, and 5-year overall survival were compared. RESULTS: A total of 884 patients who met the inclusion criteria were included in the study. Group A included 297 patients (33.60%), and 5 patients (1.68%) had CRLM. Group B included 587 patients (66.40%), and 31 patients (5.28%) had CRLM. The results of correlation analysis and logistic regression analysis showed that HBV infection (P = 0.013, HR = 0.29, 95% CI 0.11-0.77) was a protective factor for CRLM, while CEA > 5 ng/ml (P = 0.002, HR = 3.12, 95% CI 1.51-6.47) and hypertension (P = 0.010, HR = 3.50, 95% CI 1.34-9.09) were risk factors for CRLM. Group A had a significantly better 5-year liver disease-free survival than group B (P = 0.011, HR = 0.31, 95% CI 0.16-0.63), but there was no significant difference in the 5-year overall survival (P = 0.433). CONCLUSION: HBV infection may reduce the risk of metachronous liver metastasis in stage 2 colorectal cancer.

Accurate low ligation of inferior mesenteric artery and root lymph node dissection according to different vascular typing in laparoscopic radical resection of rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the feasibility and clinical significance of precision low inferior mesenteric artery (IMA) ligation with the left colonic artery (LCA) preservation and root lymph node dissection in laparoscopic radical resection for rectal cancer, according to the inferior mesenteric artery (IMA) types.</p><p><b>METHODS</b>One Hundred and fore cases of rectal cancer patients who underwent laparoscopic resection in The Sixth Affiliated Hospital of Sun Yat-sen University from October 2015 to June 2016 were selected and divided into study group and control group according to different surgical methods. The study group (52 cases) accepted precision low IMA ligation with the LCA preservation and root lymph node (No.253) dissection, according to the IMA types and length examined by preoperative computed tomography angiography (CTA) reconstruction. The control group (52 cases) accepted the traditional high IMA ligation. The perioperative efficacy indexes and postoperative recovery situation of the two groups were compared.</p><p><b>RESULTS</b>The IMA types, IMA length and preoperative clinical stages were not significantly different between the two groups (all P>0.05). The surgery was completed smoothly for patients in both groups, with no conversion to open surgery. But two patients in the study group underwent left colonic artery ligation for intra-operative need. There were no significant differences in the operative time, intra-operative blood lose, the rate of protective ileostomy and post-operative pathological stages between the two groups (all P>0.05). More total lymph nodes [(24.9±5.7) vs. (16.9±4.2), P=0.001] and No.253 lymph nodes [(2.4±1.1) vs. (1.5±0.8), P=0.001] were harvested in study group as compared to control group. However, the positive rate of total harvested lymph nodes and No.253 lymph nodes between the two groups were not significantly different (P>0.05). There were no significant differences between the two groups in postoperative first anal exhaust time, postoperative hospital stay, total volume of postoperative intraperitoneal drainage, postoperative abdominal drainage tube retention time, postoperative anal drainage tube retention time and postoperative catheter retention time (All P>0.05). There were 2 cases of postoperative dysuria and 1 case of anastomotic bleeding in study group. There were 3 cases of postoperative dysuria and 2 cases of anastomotic leak in control group. Less postoperative complications (5.8% vs. 9.6%, P<0.05) in study group as compared to control group. There was no rehospitalization or death case in two groups within 30 days after operation.</p><p><b>CONCLUSIONS</b>In the laparoscopic radical resection of rectal cancer, preserving LCA and cleaning the root lymph nodes according to IMA types, which could increase the number of harvested lymph nodes and reduce the postoperative complications was safe and effective.</p>

The expression of CIP2A in hepatocellular carcinoma and its clinical significance / 中华肝胆外科杂志

Objective This study is to explore the expression of CIP2A mRNA in hepatocellular carcinoma (HCC), and its correlations with clinicopathologic features and prognosis of HCC patients.Methods CIP2A mRNA expression was analyzed in four liver cancer cell lines (Hep-G2, MHCC97,SMMC-7721 and BEI-7402), one immortalized liver cell line L-O2, neoplastic tissues and adjacent matched non-neoplastic liver tissues in 120 HCC patients and normal liver tissues of 20 cases using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The correlations between CIP2A mRNA and clinicopathologic features and prognosis of HCC were analyzed. Results CIP2A mRNA was detected in Hep-G2, MHCC-97H, SMMC-7721 and BEL-7402, but not in L-O2.The positive rate of CIP2A mRNA expression was significantly increased in HCC tissues (78.3%)than in adjacent matched non-neoplastic liver tissues (28.3%) and normal liver tissues (5.0%,P＜0. 01). CIP2A mRNA expression was correlated with tumor size, differentiation and TNM stage (P＜0.05). Patients with positive expression of CIP2A mRNA had lower overall survival and diseasefree survival rates. Conclusions CIP2A mRNA, which is highly expressed in liver cancer cell lines and HCC tissues, may be involved in hepatocarcinogenesis. CIP2A mRNA may be a valuable biomarker for assessing the prognosis of HCC.