A novel model in predicting very early recurrence after surgical resection of hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To study the risk factors of very early recurrence (VER, within 3 months) after R 0 resection of hepatocellular carcinoma (HCC), and to establish a predictive model. Methods:Of 427 HCC patients [with 368 males, 59 females, aged (52.7±12.1) years] who developed early recurrence (within 2 years) after R 0 resection from January to December 2008 at Zhongshan Hospital, Fudan University were enrolled in the test cohort. Another 590 patients [with 525 males, 65 females, aged (54.7±11.0) years] who underwent R 0 resection from January to June 2009 were enrolled in the validation cohort. Risk factors were investigated and a predictive model was established. Results:In the test cohort, 126 patients (29.5%) developed VER and their survival outcomes were extremely poor. Serum α-fetoprotein (AFP) level >827 μg/L, multiple tumors, microvascular invasion (MVI) and tumor number were independent risk factors for VER. A new predictive model (0.809·AFP+ 1.262·tumor number+ 0.983·MVI) was established by logistic regression in predicting VER after surgery. The receiver operating characteristic curve showed that the area under the curve (AUC) in predicting VER was 0.722 (95% CI: 0.669-0.774, P<0.001). In the validation cohort, the AUC of this model was 0.785 (95% CI: 0.715-0.855, P<0.001). Conclusions:A high AFP level, multiple tumors, and MVI were independent risk factors for VER of HCC after R 0 resection. The prediction model consisting of these three factors demonstrated robustness and it has the potential in clinical application.

Immune checkpoint inhibitors for treatment of biliary malignant tumors / 临床肝胆病杂志

Biliary malignant tumors have an insidious onset and rapid development, and most patients have lost the opportunity for radical surgery at initial diagnosis and often have poor prognosis. Gemcitabine-based chemotherapy is the first-line treatment for biliary malignant tumors, but with a limited clinical effect. The improvement in next-generation sequencing technology provides the possibility for the precise treatment of biliary malignant tumors, but the application and development of the precise treatment of biliary malignant tumors are limited by the low positive rate of targets and the poor accessibility of therapeutic drugs. The advent of the era of immunotherapy represented by the immune checkpoint inhibitor PD1/PD-L1 monoclonal antibody brings a promising future for the treatment of malignant tumors, including biliary malignant tumors. Combined chemotherapy and/or targeted therapy based on immune checkpoint inhibitors has shown a good effect in the treatment of biliary malignant tumors, which is the direction of the treatment of advanced biliary malignant tumors in the future.

Expert guidance on overall management of liver cancer during the COVID-19 / 中华消化外科杂志

The pandemic of Corona Virus Disease 2019 (COVID-19) continues, which shows the concentrated or sporadic cases in multiple places. Current COVID situation is still complex. During the COVID-19, routine diagnosis and treatment of liver cancer patients has been affected in different degrees. Under the premise of following the treatment guidelines, how to reduce the risk of infection of patients and medical staff, utilize limited medical resources to maximally ensure anti-tumor treatment and related emergency treatment, and help patients get through the epidemic period is a problem for liver oncologists. Thus, experts of liver cancer treatment related disciplines of Zhongshan Hospital, Fudan University have written the Expert guidance on overall management of liver cancer during the COVID-19, which aims to provide references for liver oncolo-gists to conduct clinical work safely and effectively under the epidemic prevention and control, and to help patients fight against the epidemic smoothly.

Immunotherapy for hepacellular carcinoma: where there is hope, there is brightness / 中华消化外科杂志

China has about half of hepatocellular carcinoma (HCC) patients worldwide, and the efficay of targeted therapy and systematic chemotherapy for HCC is limited. The treatment stategies based on immune checkpoint inhibitors (ICIs) bring hope to patients. Especially, the success of ICIs plus anti-angiogenic drugs as the first-line treatment in HCC open the combinational immunotherapy model for HCC, which inludes targeted therapy, chemotherapy, radiotherapy, oncolytic virotherapy and another immunotherapy. However, most patients do not derive benefits from these agents or combinational treatments, due to innate and acquired immune resistance. The authors elaborate on hot and difficult subjects of immunotherapy for HCC, and formulate the potential striving direction. It is critical to understand the determinants driving response, resistance and adverse effects to optimize the implementation of precision immunotherapy. Overall manage-ment of HCC patients with multidesciplinary team and high integration should be strengthened. More effective immunotherapeutic strategies may be achieved though deeper understanding of the underlying immune biology, targeted drug development and new comprehensive strategies. All the above efforts are for aims and missions of"Healthy China 2030".

Connotation of Baimai disease and analysis of compatibility and usage of Baimai Ointment: based on Tibetan medicine theory / 中国中药杂志

Baimai is a complex of structure and function with the characteristics of wide distribution, complex structure, and multi-dimensional functions. Baimai, consisting of the channels in brain, the internal hidden channels connecting the viscera, and the external channels linking the limbs, governs the sensory, motor, and information transmission functions of human. According to Tibetan medicine, Baimai functions via "Long"(Qi) which moves in Baimai. "Long" is rough, light, cold, tiny, hard, and dynamic. The dysfunction of Baimai is manifested as numbness, swelling and pain, stiffness, atrophy, contracture, disability, hyperactivity, etc. The clinical manifestations of Baimai disease are facial paralysis, limb numbness, hemiplegia, contracture and rigidity, pain, opistho-tonos, paralysis, unconsciousness, head tremor, aphasia and tongue stiffness, and other abnormalities in facial consciousness, limb movement, and tactile sensation. Baimai Ointment for external use is used for the treatment of Baimai disease. It is mainly composed of medicinals which are spicy and bitter, warm, soft, mild, heavy, moist, and stable, and thus it is effective for the rough, light, cold, tiny, hard, and dynamic "Long" of Baimai disease. In clinical practice, it is mainly used for musculoskeletal diseases, such as osteoarthritis, scapulohumeral periarthritis, cervical spondylosis, low back pain, myofascitis, and tenosynovitis, nervous system diseases, such as paralysis and shoulder-hand syndrome, and limb stiffness caused by stroke, spastic cerebral palsy, trigeminal neuralgia, and facial neuritis, and limb motor and sensory dysfunction caused by trauma. According to the main symptoms of Baimai disease such as stiffness, rigidity, contraction, numbness, sensory disturbance and pain, clinicians should apply the Baimai Ointment via the inunction treatment of Tibetan medicine and in combination with Huo'ermai therapy and physiotherapy.

Herbal Textual Research on Zingiberis Rhizoma Recens in Famous Classical Formulas and Its Quality Evaluation / 中国实验方剂学杂志

ObjectiveTo provide references for the selection of Zingiberis Rhizoma Recens on the research of famous classical formulas and the reasonable uses for medicines and foods through herbal textural research and quality analysis of Zingiberis Rhizoma Recens from main producing areas in China. MethodBy consulting the ancient and modern literature， the name， origin， producing areas， harvest time， processing methods of Zingiberis Rhizoma Recens were summarized. According to the 2020 edition of Chinese Pharmacopoeia， the contents of 6-gingerol， 8-gingerol， 10-gingerol， and volatile oil in Zingiberis Rhizoma Recens samples were determined. ResultHerbal textural research indicated that medicinal Zingiberis Rhizoma Recens originated from the fresh rhizome of Zingiber officinale. Before Tang dynasty， Zingiberis Rhizoma Recens produced in Sichuan was the best. In the Song dynasty， Zingiberis Rhizoma Recens produced in Sichuan， Zhejiang， and Anhui was of excellent quality. The cultivation of Zingiberis Rhizoma Recens in Shandong developed during the Ming and Qing dynasties. From ancient times to the present， the harvest period extended from the autumnal equinox to the winter solstice. Quality evaluation standards of Zingiberis Rhizoma Recens were essentially the same in ancient and present documents， as those with little gluten or gluten-free and strong pungency were preferred. After determination， the contents of 6-gingerol， 8-gingerol， and 10-gingerol in 44 samples were qualified in 27 samples， with a qualified rate of 61.4%. Among them， 17 samples were unqualified in the total contents of 8-gingerol and 10-gingerol. Among these qualified samples， the content of 6-gingerol ranged from 0.067% to 0.255%， and the total contents of 8-gingerol and 10-gingerol ranged from 0.040% to 0.131%. The content of volatile oil in 36 samples were qualified in 33 samples， with a qualified rate of 91.7%. Among the qualified samples， the content of volatile oil ranged from 0.175% to 0.410%. ConclusionZingiberis Rhizoma Recens has been used as medicines and foods since ancient times， and the genuine producing areas are consistent in ancient and present times， while the quality of the products， especially the medicinal Zingiberis Rhizoma Recens， should be monitored. Medicinal Zingiberis Rhizoma Recens planted in Leshan city of Sichuan province contains high contents of effective components， followed by Qujing and Wenshan cities of Yunnan province. Zingiberis Rhizoma Recens planted in Shandong and other places is mostly edible.

Analysis on Indications and Medication Regularities of Famous Classical Formula Wuzhuyu Tang Based on Modern Clinical Literature / 中国实验方剂学杂志

Wuzhuyu Tang （WZYT）， a classical traditional Chinese medicine （TCM） formula， was first recorded in Treatise on Cold Damage by the prestigious physician ZHANG Zhong-jing in the Eastern Han Dynasty， and included in Catalogue of Ancient Classical Formulas （First Batch）. WZYT is composed of four medcinals： Euodiae Fructus， Ginseng Radix et Rhizoma， Zingiberis Rhizoma Recens， and Jujubae Fructus， which has the effects of warming the middle and tonifying deficiency， dissipating cold and descending adverse qi. Based on data mining， this paper analyzes the modern clinical research literature on WZYT， which is expected to lay a basis for clarifying the "disease-symptom-prescription-medicinal" relationship of WZYT， as well as its modern clinical indications and clinical dosage. With the search term "Wuzhuyu Tang"， 253 complete medical records were retrieved from CNKI， VIP， and Wanfang （2000-2020）， involving 292 TCM prescriptions. Microsoft Excel 2019 was employed to establish the medical record database and the main clinical indications were statistically analyzed. Moreover， the syndromes， incidence law， and medication regularity were summed up. The result indicates WZYT has a wide range of modern clinical applications， mainly including the treatment of headache， dizziness， vomiting， diarrhea， dysmenorrhea， morning sickness， and other diseases， and the "deficiency， cold， and reversal" symptoms， mainly manifested as nausea and vomiting， headache， fatigue and lack of strength， reversal cold of hands and feet， poor appetite， gloomy complexion， dizziness， aversion to wind and cold， abdominal pain， sloppy diarrhea， abdominal distension， poor sleep， pale tongue， white coating， and deep thread wiry pulse. These diseases and symptoms mainly occur in women and middle-aged people. In most cases， medicinals are added or subtracted according to the symptoms， and the common doses of Euodiae Fructus， Zingiberis Rhizoma Recens， Codonopsis Radix or Ginseng Radix et Rhizoma， and Jujubae Fructus in the original prescription are 6-15 g， 10-15 g， 10-15 g or 9-12 g， and 4-6， respectively. The added medicinals are in the descending order of Pinelliae Rhizoma， Atractylodis Macrocephalae Rhizoma， Poria， Glycyrrhize Radix et Rhizoma， and Chuanxiong Rhizoma according to the frequency.

The use of portal vein embolization combined with lenvatinib and a PD-1 inhibitor to treat patients with initially unresectable hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To study the safety and treatment outcomes of portal vein embolization (PVE) combined with lenvatinib plus an anti-programmed death-1(PD-1) antibody to treat patients with initially unreasectable hepatocellular carcinoma (uHCC).Methods:This study retrospectively analyzed the data of six patients with uHCC who received first-line combined systemic therapy with lenvatinib plus an anti-PD-1 antibody, and then underwent pre-hepatectomy PVE at the Department of Liver Surgery at Zhongshan Hospital, Fudan University from May 2019 to November 2020. All enrolled patients were males, aged (54.6±6.2) (ranged 46 to 63) years. Tumor response and liver volume were evaluated by medical imagings once every 2 months (±2 weeks) and evaluated using the Response Evaluation Criteria in Solid Tumours (version 1.1). Patients were followed-up by outpatient interviews or by phone calls to record their survival and tumor outcome status.Results:Three of the six enrolled patients had Barcelona Clinic Liver Cancer stage A and three had stage B disease. One patient achieved a partial response and five patients had stable diseases. The mean ± s. d. future liver remnant (FLR) percentage was (29.0±8.9) % before PVE and the combination therapy, and was (41.3±10.8) % before the last evaluation for liver surgery ( t=10.79, P<0.001). Hepatectomy was carried out in five patients, and one patient who failed to develop significant FLR hypertrophy did not undergo hepatectomy. Grade B post-hepatectomy liver failure and major postoperative complications (i.e. pleural effusion requiring additional percutaneous drainage) occurred in one patient. After a median post-operative follow-up of 4.5 (range: 1.0-12.3) months, all five patients were alive and were tumor free. Conclusion:PVE followed by hepatectomy is feasible in a uHCC patients receiving systemic therapy with lenvatinib and an anti-PD-1 antibody.

Analysis of the risk factors influencing the prognosis of patients with recurrent hepatocellular carcinoma after liver transplantation within Fudan criteria and summary of relevant clinical experience / 中华器官移植杂志

Objective:To explore the risk factors influencing the prognosis for patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation and summarize the relevant diagnostic and therapeutic experiences.Methods:The clinicopathological features with diagnosis and treatment plan of 102 recurrent HCC patients fulfilling the Fudan Criteria were compared for survival rate (univariate analysis) and independent prognostic indicators were obtained by Cox multivariate analysis.Results:The 1/3/5-year overall survival rates were 92.2%, 48.6% and 34.6% and the 1/3/5-year survival rates with tumor were 63.2%, 31.0% and 16.7% respectively. Cox regression analysis indicated that patient age, whether tumor can be surgically resected or not and personalized diagnostic & therapeutic plan based upon targeted therapy were independent prognostic factors affecting the overall survival rates and survival rates with tumor.Conclusions:Although HCC recurrence and metastasis after liver transplantation seriously influence patient prognosis, satisfactory outcomes may be obtained for some patients through active, effective and precise managements.

Clinical efficacy of combination therapy with lenvatinib and programmed death-1 antibodies in unresectable or advanced hepatocellular carcinoma / 中华消化外科杂志

Objective:To investigate the clinical efficacy of the combination therapy of lenvatinib and programmed death-1 (PD-1) antibodies in unresectable or advanced hepatocellular carcinoma (HCC).Methods:The retrospective and descriptive study was conducted. The clinico-pathological data of 59 patients with unresectable or advanced HCC who were admitted to Zhongshan Hospital of Fudan University from September 2018 to January 2020 were collected. There were 54 males and 5 females, aged from 25 to 73 years, with a median age of 52 years. All 59 patients underwent combination therapy with lenvatinib and PD-1 antibodies including 43 cases undergoing first-line therapy and 16 cases who cannot tolerate first-line therapy or with tumor progressed after first-line therapy undergoing second-line therapy. Observation indicators: (1) clinical efficacy; (2) adverse drug reactions and treatment; (3) follow-up and survival. Follow-up was performed using outpatient examination or telephone interview to detect tumor diameter of the target lesion, overall survival and progression free survival of patients up to December 2020. Measurement data with skewed distribution were expressed as M ( P25,P75) or M (range). Count data were represented as absolute numbers and (or) percentages. The Kaplan-Meier method was used to calculate the median duration of response (DoR), median overall survival time, median progression free survival time, survival rates and draw survival curves. Results:(1) Clinical efficacy: the objective response rate (ORR), complete response rate (CR), partial response rate (PR), stable disease rate (SD), progression disease rate (PD), time to response (TTR) and median DoR of 59 HCC patients were 37.3%(22/59), 11.9%(7/59), 25.4%(15/59), 37.3%(22/59), 25.4%(15/59), 2.6 months(2.1 months, 4.0 months), 6.3 months[95% confidence interval ( CI) as 2.2 to 10.5 months], respectively. The ORR, CR, PR, SD, PD and TTR of 43 HCC patients undergoing first-line therapy were 41.9%(18/43), 16.3%(7/43), 25.6%(11/43), 37.2%(16/43),20.9%(9/43), 2.2 months(2.0 months, 3.5 months), respectively. The median DoR of 43 patients undergoing first-line therapy was not reached. The ORR, CR, PR, SD, PD, TTR and median DoR of 16 HCC patients undergoing second-line therapy were 4/16, 0, 4/16, 6/16, 6/16, 3.8 months (3.6 months, 4.1 months), 4.2 months(95% CI as 2.0 to 6.3 months), respectively. Six of 59 HCC patients underwent R 0 resection due to tumor converting to resectable HCC with the conversion and resection rate of 10.2%(6/59). Among the 6 patients, 5 cases undergoing first-line treatment had the conversion and resection rates of 11.6% (5/43) and 1 case undergoing second-line treatment had the conversion and resection rates of 1/16, respectively. (2) Adverse drug reactions and treatment: 25 of 59 HCC patients underwent 3 to 4 grade adverse drug reactions with the incidence of 42.4%(25/59). Among the 25 patients, 10 cases including 5 cases undergoing first-line therapy and 5 cases undergoing second-line therapy had the level of gamma glutamyltransferase >5×upper limit of normal (ULN), 9 cases including 4 cases undergoing first-line therapy and 5 cases undergoing second-line therapy had the level of aspartate aminotransferase >5×ULN, 5 cases including 4 cases undergoing first-line therapy and 1 case undergoing second-line therapy occurred gastrointestinal hemorrhage, 4 cases undergoing first-line therapy had the level of white blood cell count <2.0×10 9/L, 4 cases including 1 case undergoing first-line therapy and 3 cases under-going second-line therapy had the level of total bilirubin >3×ULN, 3 cases undergoing first-line therapy had the level of neutrophil count <1.0×10 9/L, 3 cases including 2 cases undergoing first-line therapy and 1 case undergoing second-line therapy occurred ascites, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy had the level of platelet count <50.0×10 9/L, 2 cases undergoing first-line therapy had the level of alanine aminotransferase >5×ULN, 2 cases undergoing first-line therapy occurred hyponatremia, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy occurred pulmonary infection, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy occurred type 1 diabetes, 1 case undergoing first-line therapy occurred hypokalemia, 1 case undergoing first-line therapy occurred myocarditis, 1 case undergoing first-line therapy occurred hypophysistis, 1 case undergoing first-line therapy occurred bullous dermatitis, 1 case undergoing first-line therapy occurred hypertension. Three of 59 HCC patients underwent 5 grade adverse drug reactions ,with the incidence of 5.1%(3/59), including 1 case undergoing first-line therapy with immune hepatitis, 1 case undergoing second-line therapy with immune pneumonia and 1 case undergoing second-line therapy with immune enteritis. Some of patients underwent multiple adverse drug reactions at the same time. Twenty five patients undergoing 3 to 4 grade adverse drug reactions were relieved with the treatment of drug reduction, drug withdrawal, symptomatic treatment or hormone therapy. Three patients undergoing 5 grade adverse drug reactions died after being treated with high-dose hormone shock and hepatoprotective treatment. (3) Follow-up and survival: all 59 patients were followed up for 1.5 to 25.2 months, with a median follow-up time of 13.3 months. Of them, patients undergoing first-line therapy were followed up for 1.9 to 25.2 months, with a median follow-up time of 13.5 months. During follow-up,20 cases undergoing first-line therapy died with the fatality rate of 46.5%(20/43). Patients undergoing second-line therapy were followed up for 1.5 to 24.4 months, with a median follow-up time of 10.8 months. During follow-up, 10 cases undergoing second-line therapy died with the fatality rate of 10/16. Up to the latest follow-up, the tumor diameter of the target lesion in all 59 patients, in patients undergoing first-line therapy and in patients undergoing second-line therapy was 75 mm(38 mm, 125 mm), 74 mm(36 mm, 116 mm), 84 mm(48 mm,150 mm), respectively. The ratio of tumor diameter of the target lesion at latest follow-up to tumor diameter of the target lesion at baseline were -9.05%(-27.3%, 19.7%), -16.1%(-28.8%, 13.6%), 13.2%(-24.7%, 23.5%) for all 59 patients, patients undergoing first-line therapy and patients undergoing second-line therapy, respectively. The median overall survival time and median progression free survival time of patients undergoing first-line therapy and patients undergoing second-line therapy were 17.1 months(95% CI as 11.0 to 23.2 months), 10.8 months(95% CI as 5.0 to 16.6 months) and 10.8 months(95% CI as 9.2 to 12.4 months), 3.0 months(95% CI as 1.6 to 4.4 months), respectively. Conclusion:For unresectable or advanced HCC, combination therapy with lenvatinib and PD-1 antibodies can obtain effective antitumor activity and less incidence of adverse drug reactions.

Chinese expert consensus on the management of immune-related adverse events of hepato-cellular carcinoma treated with immune checkpoint inhibitors (2021 edition) / 中华消化外科杂志

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Overall management strategies for liver cancer patients during the COVID-19 outbreak / 中华消化外科杂志

The Corona Virus Disease 2019 (COVID-19) that occurred December of 2019 has a wide range of impacts, and its epidemic situation is grim. China has a large population of liver cancer, accounting for 50% of new cases of liver cancer worldwide. How to ensure the diagnosis, treatment and rehabilitation of liver cancer patients while preventing and controlling the epidemic situation is an issue that urgently need specialists pay attention to. The authors propose an overall management model for patients with liver cancer, combined with their own experience, in order to guide specialists to safely and effectively carry out clinical diagnosis and treatment of liver cancer during the prevention and control of epidemics, and to help liver cancer patients receive treatment.

Mechanisms and control measures of COVID-19 related liver injuries / 中华消化外科杂志

Although the epidemic situation of Corona Virus Disease 2019 (COVID-19) has been controlled, the epidemic situation remains grim. The COVID-19 is highly infectious, with various clinical manifestations including liver injury. The authors make a preliminary investigation on the mechanisms of liver injury related to COVID-19, and put forward correspon-ding control measures for reference.

Research advances in molecular classification for precision diagnosis and treatment of hepatocellular carcinoma / 中华消化外科杂志

Hepatocellular carcinoma (HCC),a highly prevalent malignancy and one of the leading cause of cancer death in China,remains a major public health problem in the next decades.Owing to the tremendous achievements in early diagnosis,precision liver surgery,molecular targeted therapy and immunotherapy,we have witnessed significant improvements in the long-time survival of HCC patients,if properly treated.However,HCC is a highly heterogeneous disease.Even for patients within the same clinical stage,their clinical outcome and treatment efficacy vary significantly.Great efforts to improve the molecular classification of HCC patients are needed to foster precision medicine,paving the way for novel therapeutic strategies.Advances in multi-omics,single-cell analysis,molecular imaging and artificial intelligence will lead to better understanding of the molecular classification and refine precision treatment in HCC,ultimately excluding this neoplasm from the risk list of our Healthy China.

Research advances in systemic therapy for hepatocellular carcinoma in the era of precision medicine / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in clinical practice and has the features of high incidence rate, poor prognosis, and high mortality rate, and its incidence rate and mortality rate rank among the top malignant tumors in the world. High heterogeneity of HCC affects the evolution and therapeutic response of HCC. Since most HCC patients are in the advanced stage at the time of diagnosis, systemic treatment has become the main treatment option. In recent years, remarkable achievements have been made in molecular targeted therapy and immunotherapy for HCC, and the latest NCCN guidelines for the systemic treatment of HCC show that sorafenib, lenvatinib, and atezolizumab combined with bevacizumab are recommended as the first-line treatment of HCC, and regorafenib, cabozantinib, nivolumab, pembrolizumab, and ramucirumab are the second-line treatment options for HCC. In the era of precision medicine, how to select the optimal individualized systemic treatment regimen is the key problem in the systemic treatment of HCC. This article reviews the advances in the systemic treatment of HCC in the era of precision medicine and discusses the development direction of HCC treatment in the future.

Research advances in molecular classification for precision diagnosis and treatment of hepatocellular carcinoma / 中华消化外科杂志

Hepatocellular carcinoma (HCC), a highly prevalent malignancy and one of the leading cause of cancer death in China, remains a major public health problem in the next decades. Owing to the tremendous achievements in early diagnosis, precision liver surgery, molecular targeted therapy and immunotherapy, we have witnessed significant improvements in the long-time survival of HCC patients, if properly treated. However, HCC is a highly heterogeneous disease. Even for patients within the same clinical stage, their clinical outcome and treatment efficacy vary significantly. Great efforts to improve the molecular classification of HCC patients are needed to foster precision medicine, paving the way for novel therapeutic strategies. Advances in multi-omics, single-cell analysis, molecular imaging and artificial intelligence will lead to better understanding of the molecular classification and refine precision treatment in HCC, ultimately excluding this neoplasm from the risk list of our Healthy China.

Enteral nutrition support for children with acute lymphoblastic leukemia in the stage of induction chemotherapy and effect on chemotherapy complications / 中华实用儿科临床杂志

Objective@#To observe the changes in nutrition indicators and the effect on chemotherapy complications as well as the safety of enteral nutrition by way of providing enteral nutrition support for children with acute lymphoblastic leukemia (ALL) at the stage of induction chemotherapy.@*Methods@#From November 2016 to September 2017, 60 children with newly diagnosed ALL at the Hematology Oncology Center of Beijing Children′s Hospital were enrolled in this study.They were randomly divided into an experimental group and a control group, 30 cases for each group.The experimental group was given a high-calorie diet, high-quality protein, and high-medium-chain trigly-ceride enteral nutrition on the basis of a conventional low-fat diet, and the duration lasted the whole induction treatment of ALL children; while the control group was given a low-fat diet routinely.By analyzing relevant indicators before induction chemotherapy (D0), chemotherapy day 15 (D15), and after chemotherapy (D33), the changes in nutritional status and the effect on chemotherapy complications in 2 groups were investigated.@*Results@#There was no significant difference in the body mass index (BMI) and the thickness of triceps skinfold between 2 groups before and after chemotherapy (all P>0.05). The upper arm circumference increased after chemotherapy in the experimental group[before treatment: (15.80±2.63) cm, after treatment: (16.27±2.57) cm], while that of the control group decreased slightly[before chemotherapy: (17.19±3.71) cm, after chemotherapy: (17.15±3.64) cm], and the difference between 2 groups was statistically significant (P<0.05). After chemotherapy, the total protein levels in two groups decreased[the experimental group: (64.52±4.85) g/L, the control group: (61.97±4.65) g/L] which was significantly different from that before chemotherapy [the experimental group: (68.17±6.37) g/L, the control group: (68.08±5.14) g/L] (P<0.01). The total protein level of the experimental group after chemotherapy was significant higher than that in the control group (P<0.05). Both albumin levels in 2 groups increased after chemotherapy [(42.45±4.32) g/L in the experimental group and (41.15±3.73) g/L in the control group], and there was a significant difference between 2 groups before chemotherapy [(39.54±3.26) g/L in the experimental group and (40.01±4.37) g/L in the control group] (P<0.05). The level of prealbumin increased after chemotherapy in both groups [(324.57±64.328) mg/L in the experimental group and (293.07±69.09) mg/L in the control group] compared with that before chemotherapy [(121.10±35.13) mg/L in the experimental group and(131.20±52.77) mg/L in the control group]. The change was statistically significant (P<0.01). The albumin level in the experimental group before chemotherapy was lower than that in the control group after chemotherapy, but it was higher than that in the control group after chemotherapy.Protein differences were statistically significant (P<0.05). The reduction rate of elemental iron in the experimental group after chemotherapy was lower than that in the control group, but it was not statistically significant (P>0.05). Elemental zinc was not significantly different compared with the control group.The incidence of neutropenia after chemotherapy in ALL children was higher (37/60 cases, 61.67%). The recovery of neutropenia after chemotherapy in the experimental group was better than that in the control group.After chemotherapy, the severity of anemia in the experimental group was lighter than that in the control group.The amount of blood transfusion required and amount of transfusion per capita were less than those in the control group (54 person-times vs.74 person-times, 2.45 times vs.3.08 times). The total number of transfused blood products was less than that of the control group (78 person-times vs.101 person-times), but none of the findings above were statistically significant (all P>0.05). The degree of hepatic damage in the experimental group decreased after chemotherapy, but there was no significant change in the control group.The initial activated partial thromboplastin time(APTT) prolongation in the trial group was more than that in the control group (5 cases vs.3 cases), and less than the control group (0 case vs.1 case) after chemotherapy.The frequency of fever in the experimental group during chemotherapy was less than that in the control group (6 cases vs.8 cases), and the average time of fever was shorter than that in the control group (2.8 d vs.4.1 d). None of the above findings were statistically significant (all P>0.05). During the course of chemotherapy, 0 pancreatitis occurred in the experimental group, and 1 pancreatitis occurred in the control group.There was no difference in remission rates between 2 groups of chemotherapy for 15 days and chemotherapy for 33 days.@*Conclusions@#The nutritional status of children with ALL was reduced after initial induction chemotherapy.Enteral nutrition support was helpful to maintain the nutritional status for children at the initial stage of chemotherapy, high-calorie diet, high-quality protein, and high-medium-chain triglyceride enteral nutrition support improves blood system tolerance to chemotherapy and reduces chemotherapy complications.

Secondary Metabolites of Endophytic Fungus Trichoderma harzianum Isolated from Physalis angulata / 中国实验方剂学杂志

Objective:To study the secondary metabolites of the endophytic fungus Trichoderma harzianum,which was isolated from Physalis angulata. Method:The strains were cultured in a big-scale by oscillating incubator. Then the obtained culture liquid and mycelia were extracted by EtOAC and actone,respectively. The extracts were integrated after recovery of solvents, and then the active secondary metabolites were isolated and purified by comprehensive use of open ODS flash column,sephadex LH-20,HPLC,and LC-MS analysis techniques. Their structures were identified according to their physico-chemical properties and nuclear magnetic resonance (NMR) data. The cytotoxicities of the compounds were determined by methyl thiazolyl tetrazolium(MTT) assay. Result:Ten compounds isolated from T. harzianum were identified as destruxin A2(1),destruxin B2(2),3-isobutyl-pyrrolopiperazine-2,5-dione[cyclo (leu-pro dipeptide)](3),cyclo (Phen-pro) dipeptide(4),cyclonerodiol(5),brevianamide F(6),N-acetyltryptamine(7),9-hydroxyl-(2-methylpropyl) isobutyl phthalate(8),5-hydroxy-3-hydroxymethyl-2-methyl-7-methoxychromone(9),and phenylpropionic acid(10). Compounds 1-10 didn't exhibit significant cytotoxicity to lung cancer cell line A549 in the MTT assay (IC50 ≥ 20 mg·L-1). Conclusion:All compounds were isolated from T. harzianum for the first time.

Association of high-sensitivity C-reactive protein with the increments of BMI and WC in junior high school students / 中国学校卫生

Objective@#To observe the short-term changes of Body Mass Index (BMI) and Waist Circumference (WC) in junior high school students in Harbin, and to explore its association with the changes of high-sensitivity C-reactive protein (hs-CRP) in the same period. Furthermore, to analyze the value of hs-CRP to predict the BMI and WC changes in children and adolescents.@*Methods@#Convenient sampling method was used,and the students in grades 6 and 7 in junior high school in Harbin were selected by stratified clicstering. Physical examination and serum hs-CRP were performed for two consecutive years. According to the results of the two surveys, the subjects were divided into control group (normal → normal), case group (abnormal → abnormal), improved group (abnormal → normal) and progression group (normal → abnormal). The multinomial logistic regression was used to analyze the predictive value of hs-CRP changes for BMI and WC changes.@*Results@#The rate of overweight and obesity among samples from junior high school was 30.6%. The increment of BMI in female was more obvious than that in male(U=17 358.0，P<0.05). Both increments in BMI and WC were positively correlated with increments in hs-CRP(P<0.05). The risk of occurrence of "BMI always abnormal" and "WC always abnormal" increased sequentially in hs-CRP "normal → abnormal", "abnormal → normal" and "abnormal → abnormal", were 3.45 times, 5.98 times and 38.84 times of "BMI is always normal", respectively; and were 3.45 times, 4.26 times and 28.50 times of "WC is always normal", respectively. The risk of "BMI improvement" was 7.70 times more than that of BMI "always normal" when hs-CRP "abnormal → normal".@*Conclusion@#The prevalence of overweight and obesity in junior high school students in Harbin is high. The BMI increases faster in female from junior high school. The trends of change of BMI and WC are consistent with the trend of change of hs-CRP. The “hs-CRP change” has a good predictive value for BMI and WC development.

The advances in diagnosis, treatment and clinical research of hepatocellular carcinoma in China / 中国实用外科杂志

As one of the high frequent malignancies in China,liver cancer has different disease background and clinicalmanagement modalities compared with that in foreigncountries. In recent years,China has made great progress inthe diagnosis and treatment of liver cancer. In the earlydiagnosis,a series of accomplishments have been achieved inliquid biopsy techniques represented by circulating micro RNA(mi RNA), circulating tumor cell(CTC),and circulating tumorDNA(ctDNA),which remarkably promoted the early diagnosis of liver cancer. In the surgical treatment,through continuousexploration of novel surgical methods,surgical indications andanti-recurrence and-metastasis strategies,patients get moresurgical opportunities,lower risks of metastasis and relapseand significantly prolonged overall survival. In addition,clinical research of liver cancer has received unprecedentedattention. The conclusions of some clinical trials have servedas important evidence to direct the development of guidelines,and to choose appropriate treatment strategies for patients inChina,which is more in line with the characteristics of livercancer in China.