Glutamine synthetase-negative hepatocellular carcinoma has better prognosis and response to sorafenib treatment after hepatectomy / 中华医学杂志(英文版)

BACKGROUND@#Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear.@*METHODS@#We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted.@*RESULTS@#Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways.@*CONCLUSIONS@#GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.

Research progress on vascularization of organoids / 生物医学工程学杂志

Organoids are three-dimensional structures formed by self-organizing growth of cells in vitro, which own many structures and functions similar with those of corresponding in vivo organs. Although the organoid culture technologies are rapidly developed and the original cells are abundant, the organoid cultured by current technologies are rather different with the real organs, which limits their application. The major challenges of organoid cultures are the immature tissue structure and restricted growth, both of which are caused by poor functional vasculature. Therefore, how to develop the vascularization of organoids has become an urgent problem. We presently reviewed the progresses on the original cells of organoids and the current methods to develop organoids vascularization, which provide clues to solve the above-mentioned problems.

Research progress of tumor derived exosomes in clinical diagnosis and treatment / 国际外科学杂志

Exosomes are extracellular vesicles containing DNA, RNA and protein. They participate in intercellular communication and play an important role in tumor growth and metastasis. Exosomes exist in a variety of body fluids. Blood, urine and cerebrospinal fluid can be separated and extracted. Exosomes derived from tumor cells have the characteristics of tumor cells. Studies have shown that exosomes are involved in many processes of tumorigenesis and development, including information transmission between tumor cells, invasion and metastasis of tumor cells. Exosomes can also be used as carriers to deliver drugs to target cells, which has the potential of targeted therapy. In the process of tumor treatment, drugs can be designed based on the targeted recognition characteristics of exosomes, so as to improve the bioavailability of anti-tumor drugs, reduce adverse reactions and enhance the therapeutic effect. The research and application of exosomes are very challenging. There is a huge heterogeneity in the types, sizes and sources of exosomes, and the production mechanism is also very complex. This paper reviews the extraction and identification methods of exosomes, and reviews the clinical application of tumor derived exosomes.

Tenofovir vs. entecavir on recurrence of hepatitis B virus-related hepatocellular carcinoma beyond Milan criteria after hepatectomy / 中华医学杂志(英文版)

BACKGROUND@#Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria.@*METHODS@#Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan-Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence.@*RESULTS@#The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P = 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS.@*CONCLUSIONS@#Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.

The implementation of multi-disciplinary treatment and whole course management in hepatocellular carcinoma / 中华肝胆外科杂志

In China, hepatocellular carcinoma (HCC) accounts for about 50% of cases in the world, which is still challenging. The implementation of multi-disciplinary treatment (MDT) and whole course management of HCC are conducive to improve the prognosis of patients, so as to achieve the goal of increasing by 15% of overall survival of HCC patients as proposed by the "Healthy China 2030" . The standardized management of HCC includes several key points, such as exact diagnosis of the HCC, selection of proper treatment methods, individual postoperative adjuvant therapy and regular follow-up. MDT is the key measure to implement the standardized and whole course management of HCC. Herein, the author tends to summary the experience on standardized management of HCC.

Nomograms to Predict the Individual Survival of Patients with Solitary Hepatocellular Carcinoma after Hepatectomy

BACKGROUND/AIMS: Solitary hepatocellular carcinoma (HCC) is a subgroup of HCCs. We aimed to establish nomograms for predicting the survival of solitary HCC patients after hepatectomy. METHODS: A total of 538 solitary HCC patients were randomly classified into training and validation sets. A Cox model was used to identify predictors of overall survival (OS) in the training set. A nomogram was generated based on these predictors and was validated using the validation set. RESULTS: Tumor size, microvascular invasion, and major vascular invasion were significantly associated with OS in the training set. Nomograms were developed based on these predictors in the multivariate analysis. The C-index was 0.75 for the OS nomogram and 0.72 for the recurrence-free survival nomogram. Compared to the index of conventional staging systems for predicting survival (0.71 for Barcelona Clinic Liver Cancer, 0.66 for the seventh American Joint Committee on Cancer, 0.68 for Cancer of the Liver Italian Program, and 0.70 for Hong Kong Liver Cancer), the index of the OS nomogram was significantly higher. Moreover, the calibration curve fitted well between the predicted and observed survival rate. Similarly, in the validation set, the nomogram discrimination was superior to those of the four staging systems (p<0.001). CONCLUSIONS: The nomograms demonstrated good discrimination performance in predicting 3- and 5-year survival rates for solitary HCCs after hepatectomy.

Phenotype and genotype features of 187 patients with spinocerebellar ataxia type 3 / 中华神经医学杂志

Objective To discuss the genotype and phenotype features of 187 patients with spinocerebellar ataxia type 3 (SCA3) and analyze their genotype-phenotype relationship.Methods A total of 187 patients genetically diagnosed as having SCA3 from 160 families were enrolled from our hospital from 2005 to 2015.Detailed medical histories were collected.SPSS 22.0 was conducted to statistically analyze the genotypes and pathogenic CAG expansions of A TXN3 gene in the patients.Results One hundred males and 87 females suffered SCA3.Mean age at onset was 35.43±11.17 years.The ranges of pathogenic CAG expansion were 65-86 repeats,with mean pathogenic CAG expansion of 74.11±3.56 repeats.A negative correlation was found between number of CAG repeats and age of onset (r=-0.815,P=0.000).Frequencies of the patients with tendon hyporeflexia were 28.9％ and 6.0％,respectively,in the smaller pathogenic CAG expansion group (≤74) and larger pathogenic CAG expansion group (＞74),with significant difference (P＜0.05).Frequencies of patients with rigidity were 27.8％ and 49.4％,respectively,in the smaller pathogenic CAG expansion group and larger pathogenic CAG expansion group,with significant difference (P＜0.05).Conclusions SCA3 is neurodegenerative disorder with high clinical and genetical heterogeneity.There are distinct correlations between number of pathogenic CAG expansion and age of onset,frequency ofhyporeflexia and rigidity.

Design and Implement of the ECLSS Adaptive Learning Intelligent Decision Support System / 航天医学与医学工程

Objective To monitor state of environment control and life support system (ECLSS), and to diagnose faults and provide decision support in manned space flight. Methods According to the principle of decision support system, neural networks and the expert system, the foundational constructional structure and work flow of the ECLSS decision support system(EDSS) were designed,fault tree analyze(FTA) method was used to sort all of the faults and to form the expert knowledge framework, expert system and neural networks were integrated to adaptive learning from experience. Results In the two-men-five-days SZ-6 manned space flight, this software system worked well, and had reduced the difficulty and intensity of ground flight control and had provided good technological support for the consummation of this flight. Conclusion For the first time, the ECLSS decision support system is designed and implemented by using database and expert system technology. It can judge parameters state and diagnose faults exactly and rapidly, and the data models are designed correctly to give the rational result of parameter prediction.