Objective To study the anatomical variations adjacent to the umbilical portion of the left portal vein (U-point) radiologically and to determine their impact on treatment of hilar cholangiocarcinoma (HCCA).Methods From January 2014 to February 2016,47 consecutive patients who were diagnosed to suffer from Bismuth type Ⅰ,Ⅱ or Ⅲ a HCCA in our institution were retrospectively studied.All these patients underwent enhanced CT examination preoperatively and three-dimensional (3D) models were then reconstructed.Results Any variations of the left biliary system in relation to the U-point were analyzed.The findings showed that:B2 and B3 united above or lateral to the U-point in 31 patients (65.9％);B2 and B3 united medial to the U-point in 4 patients (8.5％);and B4 converged into B3 prior to B2 in 6 patients (12.8％).Rare variations were observed in 6 patients (12.8％).For the confluence patterns of B4:the central type was found in 10 patients (21.3％),the peripheral type in 35 patients (74.5％) and the combined type in 2 patients (4.2％).Analysis of the relationship between B1l and the confluence of B2 and B3 showed the distance to be (31.6 ± 6.2) mm in the above or the lateral patterns and (13.7 ± 4.7) mm in the medial pattern.The difference was significant (P ＜0.05).The distance from B1l to B4 was (7.1 ± 2.0) mm in the central and combined types but (16.4 ±4.0) mm in the peripheral type.The difference was significant (P ＜ 0.05).The left hepatic artery showed variations in the origin and course pattern in 4 (8.5％) and 6 patients (12.8％),respectively.The two-dimensional (2D) and 3D imagings showed excellent consistency in the evaluation of variations of the left biliary system in relation to the U-point and the left hepatic artery.Conclusions It is very important to know the variations of the left biliary and the vascular systems adjacent to the U-point in preoperative evaluating on resectability of HCCA.An accurate assessment could be accomplished using 2D imaging alone.However,3D reconstruction is a useful technique to use in complex case with locally advanced tumors.

Objective To investigate the clinical featurcs of hepatic perivascular epithelioid cell carcinoma (PEComa) and the experiments in the surgical treatment of PEComa.Methods The clinical data of 16 patients with hepatic PEComa who received surgical treatment at the First Affiliated Hospital of Nanjing Medical University from January 2008 to January 2012 were retrospectively analyzed.The incidence,clinical manifestations,imagiong characteristics,surgical outcomes and pathological manifestations of this disease were analyzed.B sonography,hepatic function test,tumor markers test and epigastric computed tomography (CT) were applied to detect tumor recurrence and metastasis.The follow-up was ended in December 2012.Result Middle aged and female patients took large part of the patients.Of the 16 patients,8 had no subjective symptoms,and other patients had discomfort in the right upper quadrant,pain or tenderness of the liver.All the tumors were solitary,and most of them located at the right liver (11 tumors were in the right liver,4 in the left liver,1 in the caudate lobe).No specific features were detected by preoperative B sonography,while inhomogeneous low density in the tumor region was detected on by CT.All the patients received partial liver resection without morbidity and morality.The results of immunohistochemistry showed that thc expressions of HMB-45,Melan-A and vascular smooth muscle actin were positive.The mean time of follow-up was 27.9 months (range,9.0-46.0 months),no tumor recurrence and death was observed during the follow-up.Conclusions Middle aged females are susceptive to hepatic PEComa,and patients have no specific clinical presentations.Preoperative CT examination is helpful for differential diagnosis of PEComa,and partical hepatectomy can achieve satisfactory short-term clinical outcomes.

This study aimed to investigate whether β-elemene could improve the dysfunction of vascular endothelial cells induced by low shear force (LSS), and the proliferation and migration of vascular smooth muscle cells induced by oxidized low-density lipoprotein (ox-LDL). Parallel plate flow chambers and ox-LDL were used to establish vascular endothelial cells (ECs) dysfunction model and vascular smooth muscle cell (VSMCs) proliferation and migration model, respectively, and the effects of β-elemene on ECs dysfunction and VSMCs proliferation and migration were examined. The activity of ROS in ECs was measured by DHE and the activity of NO in ECs was tested by DAF-FM DA. The protein phosphorylation of Akt and ERK in ECs were detected by Western blot. The proliferation of VSMCs was measured by MTT. The migration of VSMCs was examined by cell scratch test and Transwell assay. The gene expression of MMP-2 and MMP-9 in VSMCs was measured by RT-qPCR. In ECs, β-elemene could significantly reduce the LSS-induced increase in ROS, significantly increase the LSS-induced decrease in NO, decrease the phosphorylation of ERK, and increase the phosphorylation of Akt. In VSMCs, β-elemene could significantly reduce the proliferation and migration of VSMCs induced by ox-LDL, and reduce the gene expression of MMP-2 and MMP-9. To conclude, β-elemene can improve the LSS-induced ECs dysfunction and ox-LDL-induced VSMCs proliferation and migration.

Hepatobiliary surgery is considered to be technically challenging because of complex intrahepatic and perihilar anatomical structures and variations.Nowadays, three-dimensional imaging technique plays an important role in the time of precise liver surgery.Three-dimensional images depict the spatial location of tumor, and the course, confluence pattern and variation of portal vein, hepatic artery, biliary system and hepatic vein distinctly while showing involved hepatic segments and the relationship with adjacent vessels from omnidirectional view, measuring the length of margin and future remnant liver.With the help of surgical simulation, surgeons can determine the significant vessels preoperatively.The application of three-dimensional imaging technique may improve the resectability and safety of complex hepatobiliary surgery, such as hilar cholangiocarcinoma, centrally located liver tumor, hepatolithiasis and living donor liver transplantation.Meanwhile, three-dimensional visualization facilitates the understanding of two-dimensional images and complicated surgical anatomy for surgeons.

To explore the effect of intensive insulin therapy (IIT) on high mobility group box-1/nuclear factor-κB (HMGB1/NF-κB) signaling pathway in severe traumatic brain injury (sTBI) patient with stress hyperglycemia. Methods Sixty-one sTBI patients with stress hyperglycemia [Glasgow coma scale (GCS) ≤ 8, three times of random blood glucose levels > 11.1 mmoL/L, glycosylated hemoglobin (HbA1c) < 0.065] admitted to the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University from July 2015 to October 2017 were enrolled. Patients were divided into IIT group (29 cases, keeping blood glucose at 4.4-7.8 mmol/L) and conventional glycemic therapy (CGT) group (32 cases, keeping blood glucose at 7.8-12.2 mmo/L) according to the random number table method. Before treatment and 1, 7 and 14 days after treatment, the levels of plasma HMGB1 and tumor necrosis factor-α (TNF-α) were measured by enzyme linked immunosorbent assay (ELISA); C-reactive protein (CRP) was determined by automatic biochemical analyzer, and NF-κB p65 gene expression in peripheral blood mononuclear cells was detected by real-time quantitative polymerase chain reaction (PCR). Results Nine patients were withdrawn from the observation because the 4 consecutive blood glucose monitoring did not reach the target value, combined with severe infection, or abandoned the treatment with serious brain damage. Finally, 52 patients were enrolled in the analysis, including 28 in CGT group and 24 in IIT group. The levels of plasma HMGB1, TNF-α, CRP and the expression of NF-κB gene in monocytes of the two groups at 1 day after treatment were significantly higher than those before treatment, and reached the peak value, then gradually decreased. After 7 days of treatment, they were significantly lower than 1 day. The levels of plasma CRP and TNF-α in the IIT group were significantly lower than those in the CGT group [CRP (mg/L): 36.7±4.4 vs. 45.1±6.1, TNF-α (ng/L): 42.4±9.7 vs. 53.2±9.1, both P < 0.05], the level of HMGB1 in plasma and the expression of NF-κB p65 in monocytes were significantly lower than those in the CGT group after 14 days of treatment [HMGB1 (μg/L): 60.1±8.7 vs. 80.5±9.1, NF-κB p65 (ΔCt): 35.8±8.5 vs. 53.5±7.3, both P < 0.05]. Conclusion IIT inhibits the inflammatory response in sTBI patients with stress hyperglycemia through HMGB1/NF-κB pathway.

Objective:To analyze the clinical characteristics of monkeypox patients.Methods:The clinical data and laboratory findings of 4 patients with monkeypox patients diagnosed at Yiwu Central Hospital in July 2023 were analyzed. Herpes fluid and skin tissue samples were collected, the viruses were isolation and cultured in African green monkey kidney cells (Vero) and identified with whole gene sequencing.Results:All four patients were male, aged 24-35 years. All patients had male-to-male behavior within 21 days before onset of the disease. Among them, one patient has AIDS and one patient has syphilis. Four patients presented with perineal skin lesions with itching, and 3 patients were found to have enlarged lymph nodes upon admission. Laboratory testing: lymphocyte abnormality (4.57×10 9/L) in 1 case; increased procalcitonin (0.25 ng/mL) in 1 case; elevated IL-10 levels ( 7.11 ng/L and 9.42 ng/L) in 2 cases; increased IL-6 (66 ng/L) and IL-4 (3.24 ng/L) in 1 case, respectively. One case had abnormal myocardial zymogram with a elevated lactate dehydrogenase level of 313 U/L. The monkeypox virus was isolated from lesion tissue and herpes fluid, and the whole gene sequencing identified it as the B. 1.3 subtype of the IIb evolutionary branch, exhibiting typical pathological effects on Vero cells. Conclusion:The clinical manifestations of the 4 monkeypox patients confirmed in Zhejiang province are mild, patients had a definitive history of male-to-male sexual behavior and the virus strains belong to the B. 1.3 lineage of the IIb evolutionary branch.

The treatment of hepatobiliary malignant tumor is characterized by the coexistence of multiple treatment methods and multiple disciplines. In order to evaluate the clinical efficacy of different treatment measures or multiple treatment combinations, and to promote the standardized development of comprehensive treatment patterns for hepatobiliary malignant tumor, the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University constructs the registry and follow-up database in hepatobiliary tumor patients based on the information-based platform of the hospital, which will help guide clinicians to make scientific decisions and improve the level of clinical diagnosis and treatment. This study describes the framework design, function modules, data acquisition process and quality control of the database of hepatobiliary malignant tumor. Based on the observational bidirectional cohort study design, the previous clinical data can be sorted to match the current database, on the other hand, the clinical data can be prospectively collected including basic information, admission evaluation, surgical information and postoperative situation, comprehensive treatment measures, regular reexaminations and long-term follow-up, etc. The data quality control system can be improved by formulating standardized operation procedures, regularly personnel training and full-process data management plans. This database will provide high-quality real-world data for clinicians, researchers, and guideline experts, and then provide high-level medical evidence for the standardized development of comprehensive treatment patterns of hepatobiliary malignancies.

Angucyclines/angucyclinones are a large group of polycyclic aromatic polyketides and their producers are widely distributed in nature. This family of natural products attracts great attention because of their diverse biological activities and unique chemical structures. With the development of synthetic biology and the exploitation of the actinomycetes from previously unexplored environments, angucyclines/angucyclinones-like natural products with new skeletons were continuously discovered, thus enriching the structural diversity of this family. In this review we summarize the new angucyclines/angucyclinones analogues discovered in the last decade (2010-2020) by using different strategies, such as changing cultivation conditions, genetic modification, genome mining, bioactivity-guided compound isolation, and fermentation of actinomycetes from underexplored environments. We also discuss the role of synthetic biology in the discovery and development of new compounds of the angucycline/angucyclinone family.
Anthraquinones ; Biological Products ; Polyketides ; Streptomyces

Background: Gastric cancer is one of the common gastrointestinal malignancies. Early diagnosis can reduce the mortality rate significantly. In the Chinese consensus published in 2017, the New Gastric Cancer Screening Scoring System was recommended to be used for risk stratification of gastric cancer. Aims: To preliminarily explore the value of the New Gastric Cancer Screening Scoring System in early gastric cancer screening in asymptomatic community population. Methods: At several communities in Suzhou City Xiangcheng District, a questionnaire survey was conducted in asymptomatic community residents willing to accept voluntary serum tests to collect information on high risk factors of gastric cancer. Serum pepsinogen (PG), PGⅡ, gastrin 17 (G-17) and Helicobacter pylori (Hp) IgG were tested simultaneously. Risk stratification of gastric cancer was carried out in accordance with the New Gastric Cancer Screening Scoring System. Gastroscopy was recommended for moderate to high risk individuals. Results: A total of 540 asymptomatic individuals completed the study, of which 11 were categorized as high risk (2.0%), 168 as moderate risk (31.1%), and 361 as low risk (66.9%). Sixty-four moderate to high risk individuals completed the gastroscopy with a response rate of 35.8%. Four precancerous lesions were detected (6.2%), including 3 gastric low-grade intraepithelial neoplasia and 1 duodenal adenoma. No gastric cancer was detected. Conclusions: The New Gastric Cancer Screening Scoring System is useful for risk stratification of gastric cancer in asymptomatic population and may provide a basis for further endoscopic examination. However, the value of this scoring system in low risk areas of gastric cancer needs to be further verified.

Objective:To summarize the experience of surgical treatment of primary liver cancer.Methods:The clinical data of 10 966 surgically managed cases with primary liver cancer, from January 1986 to December 2019 at Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, were retrospectively analyzed. The life table method was used to calculate the survival rate and postoperative recurrence rate. Log‐rank test was used to compare the survival process of different groups, and the Cox regression model was used for multivariate analysis. In addition, 2 884 cases of hepatocellular carcinoma(HCC) with more detailed follow‐up data from 2009 to 2019 were selected for survival analysis. Among 2 549 patients treated with hepatectomy, there were 2 107 males and 442 females, with an age of (56.6±11.1) years (range: 20 to 86 years). Among 335 patients treated with liver transplantation, there were 292 males and 43 females, with an age of (51.0±9.7) years (range: 21 to 73 years). The outcomes of hepatectomy versus liver transplantation, anatomic versus non-anatomic hepatectomy were compared, respectively.Results:Of the 10 966 patients with primary liver cancer, 10 331 patients underwent hepatectomy and 635 patients underwent liver transplantation. Patients with liver resection were categorized into three groups: 1986－1995(712 cases), 1996－2008(3 988 cases), 2009?2019(5 631 cases). The 5‐year overall survival rate was 32.9% in the first group(1986－1995). The 5‐year overall survival rate of resected primary liver cancer was 51.7% in the third group(2009‐2019), among which the 5‐year overal survival rates of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and mixed liver cancer were 57.4%, 26.6% and 50.6%, respectively. Further analysis was performed on 2 549 HCC patients with primary hepatectomy. The 1‐, 3‐, 5‐, and 10‐year overall survival rates were 88.1%, 71.9%, 60.0%, and 41.0%, respectively, and the perioperative mortality rate was 1.0%. Two hundred and forty‐seven HCC patients underwent primary liver transplantation, with 1‐, 3‐, 5‐, and 10‐year overall survival rates of 84.0%, 64.8%, 61.9%, and 57.6%, respectively. Eighty‐eight HCC patients underwent salvage liver transplantation, with the 1‐, 3‐, 5‐, and 10‐year overall survival rates of 86.8%, 65.2%, 52.5%, and 52.5%, respectively. There was no significant difference in survival rates between the two groups with liver transplantation ( P>0.05). Comparing the overall survival rates and recurrence rates of primary hepatectomy (2 549 cases) with primary liver transplantation (247 cases), the 1‐, 3‐, 5‐, and 10‐year overall survival rates in patients within Milan criteria treated with hepatectomy and transplantation were 96.3%, 87.1%, 76.9%, 54.7%, and 95.4%, 79.4%, 77.4%, 71.7%, respectively ( P=0.754). The 1‐, 3‐, 5‐year recurrence rates were 16.3%, 35.9%, 47.6% and 8.1%, 11.7%, 13.9%, respectively( P<0.01). The 1‐, 3‐, 5‐, 10‐year overall survival rates in patients with no large vessels invasion beyond the Milan criteria treated with liver resection and transplantation were 87.2%, 65.9%, 53.0%, 33.0% and 87.6%, 71.8%, 71.8%, 69.3%, respectively( P=0.003); the 1‐, 3‐, 5‐year recurrence rate were 39.2%, 57.8%, 69.7% and 29.7%, 36.7%, 36.7%, respectively ( P<0.01). The 1‐, 3‐, 5‐, and 10‐year overall survival rates in patients with large vessels invasion treated with liver resection and transplantation were 62.1%, 36.1%, 22.2%, 15.0% and 62.9%, 31.8%,19.9%, 0, respectively ( P=0.387); the 1‐, 3‐, 5‐year recurrence rates were 61.5%, 74.7%, 80.8% and 59.7%, 82.9%, 87.2%, respectively( P=0.909). Independent prognostic factors for both overall survival and recurrence‐free survival rates of HCC patients treated with liver resection included gender, neoadjuvant therapy, symptoms, AST, intraoperative or postoperative blood transfusion, tumor number, tumor size, cirrhosis, macrovascular invasion, microvascular invasion, and pathological differentiation. Propensity score matching analysis of 443 pairs further showed that there was no significant difference in overall survival rate between anatomical liver resection and non‐anatomical liver resection( P=0.895), but the recurrence rate of non‐anatomical liver resection was higher than that of anatomical liver resection( P=0.035). Conclusions:In the past decade, the overall survival rate of HCC undergoing surgical treatment is significantly higher than before. For HCC patients with good liver function reservation, surgical resection can be performed first, and salvage liver transplantation can be performed after recurrence. The effect of salvage liver transplantation is comparable to that of primary liver transplantation. As for the choice of liver resection approaches, non‐anatomical resection can reserve more liver tissue and can be selected as long as the negative margin is guaranteed.