1.Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics
Yu-long CHEN ; You ZHAI ; Xiao-yan WANG ; Wei-xia LI ; Hui ZHANG ; Ya-li WU ; Liu-qing YANG ; Xiao-fei CHEN ; Shu-qi ZHANG ; Lu NIU ; Ke-ran FENG ; Kun LI ; Jin-fa TANG ; Ming-liang ZHANG
Acta Pharmaceutica Sinica 2024;59(2):382-394
Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and
2.Blaps rynchopetera affects proliferation, migration, and invasion of non-small cell lung cancer: a study based on network pharmacology and in vivo and in vitro experiments.
Xiu-Yu LI ; Ke MA ; Jing-Nan YAN ; Fang-Cheng YOU ; Lu MA
China Journal of Chinese Materia Medica 2023;48(13):3576-3588
Network pharmacology, molecular docking, and in vivo and in vitro experiments were employed to study the molecular mechanism of Blaps rynchopetera Fairmaire in the treatment of non-small cell lung cancer(NSCLC). The components of B. rynchopetera were collected by literature review, and the active components were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). PharmMapper was used to obtain the targets of the active components. The targets of NSCLC were obtained from DrugBank, GeneCards, OMIM, TTD, and PharmGKB. The Venn diagram was drawn to identify the common targets shared by the active components of B. rynchopetera and NSCLC. The "drug component-target" network and protein-protein interaction(PPI) network were constructed by Cytoscape, and the key targets were screened by Centiscape. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the above key targets were performed by DAVID. AutoDock and PyMOL were used for the molecular docking between the key targets and corresponding active components. A total of 31 active components, 72 potential targets, and 11 key targets of B. rynchopetera against NSCLC were obtained. The active components of B. rynchopetera had good binding activity with key targets. Further, the serum containing B. rynchopetera was prepared and used to culture human lung adenocarcinoma A549 cells. The CCK-8 assay was employed to determine the inhibition rates on the growth of A549 cells in blank control group and those exposed to different concentrations of B. rynchopetera-containing serum, cisplatin, and drug combination(B. rynchopetera-containing serum+cisplatin) for different time periods. The cell migration and invasion of A549 cells were detected by cell scratch assay and Transwell assay, respectively. Western blot was employed to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), caspase-3, cell division cycle 42(CDC42), proto-oncogene tyrosine-protein kinase SRC, and vascular endothelial growth factor(VEGF) in A549 cells. C57BL/6 mice were inoculated with Lewis cells and randomly assigned into a model control group, a B. rynchopetera group, a cisplatin group, and a drug combination(B. rynchopetera+cisplatin) group, with 12 mice per group. The body weight and the long diameter(a) and short diameter(b) of the tumor were monitored every other day during treatment, and the tumor volume(mm~3) was calculated as 0.52ab~2. After 14 days of continuous medication, the mice were sacrificed for the collection of tumor, spleen, and thymus, and the tumor inhibition rate and immune organ indexes were calculated. The tissue morphology of tumors was observed by hematoxylin-eosin(HE) staining, and the positive expression of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF in the tumor tissue was detected by immunohistochemistry. The results indicated that B. rynchopetera and the drug combination regulated the expression levels of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF to inhibit the proliferation, migration, and invasion of A549 cells and Lewis cells, thus playing a role in the treatment of NSCLC via multiple ways.
Humans
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Animals
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Mice
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Mice, Inbred C57BL
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Carcinoma, Non-Small-Cell Lung/genetics*
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Caspase 3
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Network Pharmacology
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Vascular Endothelial Growth Factor A
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Cisplatin
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Molecular Docking Simulation
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bcl-2-Associated X Protein
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Lung Neoplasms/genetics*
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Cell Proliferation
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Drugs, Chinese Herbal/pharmacology*
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Medicine, Chinese Traditional
3.Fatty Acid Binding Protein 5 (FABP5) Promotes Aggressiveness of Gastric Cancer Through Modulation of Tumor Immunity
Mei-qing QIU ; Hui-jun WANG ; Ya-fei JU ; Li SUN ; Zhen LIU ; Tao WANG ; Shi-feng KAN ; Zhen YANG ; Ya-yun CUI ; You-qiang KE ; Hong-min HE ; Shu ZHANG
Journal of Gastric Cancer 2023;23(2):340-354
Purpose:
Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC.
Materials and Methods:
We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq).
Results:
Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokinecytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics.
Conclusions
These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.
4.Analysis of 53 cases of transjugular liver biopsy.
Lei WANG ; Zhen Dong YUE ; Hong Wei ZHAO ; Zhen Hua FAN ; Yi Fan WU ; Yu ZHANG ; Rui Zhao QI ; Ke ZHANG ; Li JIANG ; Hui Guo DING ; Yue Ning ZHANG ; Fu Quan LIU
Chinese Journal of Hepatology 2022;30(2):220-223
Objective: To investigate the practicability and safety of transjugular liver biopsy (TJLB). Methods: Data of 53 cases with transjugular liver biopsy from June 2015 to June 2020 were collected. LABS-100 was used in all patients who underwent transjugular liver biopsy. Among them, 45 cases and eight were biopsied via hepatic vein and intrahepatic segment of the inferior vena cava. The surgical indications, related complications, and postoperative pathological diagnosis were analyzed and summarized. Results: TJLB was successful in all patients, with an average of 2.8 punctures per case. Satisfactory liver tissue and histopathological diagnosis was obtained in all patients. Two cases developed a cervical hematoma that was improved spontaneously, and one patient developed an intrahepatic hematoma that was improved after conservative treatment. Conclusion: TJLB is a practical and safe method for patients with contraindications to percutaneous liver biopsy.
Biopsy/methods*
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Biopsy, Needle/methods*
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Humans
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Jugular Veins
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Liver Diseases/pathology*
5.Chemical constituents from fruits of Cornus officinalis and their anti-Alzheimer's disease activity
Meng YANG ; Zhi-you HAO ; Shi-qi ZHOU ; Bing CAO ; Deng-hui ZHU ; Ying YANG ; Jun-jun WEI ; Si-qi TAO ; Bo-wen ZHANG ; Xiao-ke ZHENG ; Wei-sheng FENG
Acta Pharmaceutica Sinica 2022;57(12):3608-3615
Fifteen compounds were isolated from fruits of
6.Life-saving therapy for complete traumatic hemipelvectomy: a case report.
Jing-Hong ZHENG ; Hong-Jiang CHEN ; Xiao-Hui LU ; Di ZHAO ; Shao-Wei LUO ; You-Bin CHEN ; Jian-Kun XU ; Wen CHEN ; Yong-Ming ZENG ; Lin-Xi HUANG ; Si CHEN ; Wei-Qi KE ; Jun HU
Chinese Medical Journal 2021;134(11):1376-1378
7.Clinical effect of multicenter multidisciplinary treatment in children with renal malignant tumors.
Ze-Xi YIN ; Xiang-Ling HE ; Jun HE ; Xin TIAN ; Cheng-Guang ZHU ; Ke-Ke CHEN ; Run-Ying ZOU ; Ya-Lan YOU ; Xin-Ping JIANG ; Wen-Fang TANG ; Min-Hui ZENG ; Zhi-Jun HUANG ; An-Qi YAO
Chinese Journal of Contemporary Pediatrics 2021;23(2):169-173
OBJECTIVE:
To study the long-term clinical effect of multicenter multidisciplinary treatment (MDT) in children with renal malignant tumors.
METHODS:
A retrospective analysis was performed on the medical data of 55 children with renal malignant tumors who were diagnosed and treated with MDT in 3 hospitals in Hunan Province from January 2015 to January 2020, with GD-WT-2010 and CCCG-WT-2016 for treatment regimens. A Kaplan-Meier survival analysis was used to analyze the survival of the children.
RESULTS:
Of the 55 children, 10 had stage I tumor, 14 had stage Ⅱ tumor, 22 had stage Ⅲ tumor, 7 had stage IV tumor, and 2 had stage V tumor. As for pathological type, 47 had FH type and 8 had UFH type. All children underwent complete tumor resection. Of the 55 children, 14 (25%) received preoperative chemotherapy. All children, except 1 child with renal cell carcinoma, received postoperative chemotherapy. Among the 31 children with indication for radiotherapy, 21 (68%) received postoperative radiotherapy. One child died of postoperative metastasis. The incidence rate of FH-type myelosuppression was 94.4%, and the incidence rate of UFH-type myelosuppression was 100%. The median follow-up time was 21 months and the median survival time was 26 months for all children, with an overall survival rate of 98% and an event-free survival rate of 95%.
CONCLUSIONS
Multicenter MDT has the advantages of high success rate of operation and good therapeutic effect of chemotherapy in the treatment of children with renal malignant tumors, with myelosuppression as the most common side effects, and radiotherapy is safe and effective with few adverse events. Therefore, MDT has good feasibility, safety, and economy.
Child
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Family
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Humans
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Kidney Neoplasms/therapy*
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Progression-Free Survival
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Retrospective Studies
8.Analysis on Related Factors of Pulmonary Infection in Patients with Multiple Myeloma Treated with Bortezomib.
Gao LI ; Qi-Ke ZHANG ; Xiao-Fang WEI ; You-Fan FENG ; Wen-Hui YANG ; Yan-Qing SUN
Journal of Experimental Hematology 2021;29(1):152-157
OBJECTIVE:
To analyze the risk factors, distribution of pathogenic strains and tolerance of pulmonary infection in patients with multiple myeloma(MM) during bortezomib chemotherapy.
METHODS:
The clinical data of 85 patients with multiple myeloma treated by bortezomib in our hospital from January 2015 to January 2019 was analyzed. The patients were divided into infection group and control group according to whether they were infected. The tolerance, pathogen distribution, and related risk factors were retrospectively analyzed.
RESULTS:
Pulmonary infection rate was 55.29% in 85 MM patients. The proportions of the patients with anemia, neutropenia, and ECOG score ≥2 points in the infection group were significantly higher than those in the control group (P<0.05). In this study, 30 strains of pathogenic bacteria were detected, with gram-negative bacteria accounting for 60%, gram-positive bacteria for 33.33%, fungi for 3.3% and tuberculosis bacteria for 3.3%. Pseudomonas aeruginosa, klebsiella pneumoniae, streptococcus pneumoniae, staphylococcus aureus accounted showed the highest proportion. Most of MM patients with pulmonary infection showed a heterprognosis after two weeks antibiotic treatment, while 3 patients died. About 30 percent of early deaths were due to pulmonary infections.
CONCLUSION
Anemia, neutropenia, ECOG score ≥2 points are the major clinical characteristics of the multiple myeloma patients with pulmonary infections. Pulmonary infection is an important cause of early death in patients with multiple myeloma. Pathogenic bacteria are mainly composed of gram-negative bacteria. Beta-lacta/ beta-lactamase inhibitor combinations or Carbapenems are effective empiric treatment for controlling the progression of pulmonary infection.
Bortezomib
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Drug Resistance, Bacterial
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Humans
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Microbial Sensitivity Tests
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Multiple Myeloma/drug therapy*
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Retrospective Studies
9.Questionnaire investigation of radiation rectal injury with anxiety, depression and somatic disorder.
Bo LIAN ; Xin Ping CAO ; Hai Jun DENG ; Jun JIANG ; Ke Wei JIANG ; Xin Xiang LI ; You Sheng LI ; Guo Le LIN ; Ji Hong LIU ; Shou Min BAI ; Feng WANG ; Zi Qiang WANG ; Ai Wen WU ; Yi XIAO ; Hong Wei YAO ; Wei Tang YUAN ; Wei ZHANG ; Zhen ZHANG ; Yan Bing ZHOU ; Teng Hui MA ; Qing Chuan ZHAO
Chinese Journal of Gastrointestinal Surgery 2021;24(11):984-990
Objective: To observe the incidence and treatment of radiation rectal injury complicated with anxiety, depression and somatic symptom disorder. Methods: A cross-sectional survey research method was carried out. Patients with radiation rectal injury managed by members of the editorial board of Chinese Journal of Gastrointestinal Surgery were the subjects of investigation. The inclusion criteria of the survey subjects: (1) patients suffered from pelvic tumors and received pelvic radiotherapy; (2) colonoscopy showed inflammatory reaction or ulcer in the rectum. Exclusion criteria: (1) patient had a history of psycho-somatic disease before radiotherapy; (2) patient was unable to use a smart phone, unable to read and understand the questions in the questionnaire displayed on the phone; (3) patient refused to sign an informed consent form. According to the SOMA self-rating scale, PHQ-15 self-rating scale, GAD-7 and PHQ-9 self-rating scale, the electronic questionnaire of "Psychological Survey of Radiation Proctitis" was designed. The questionnaire was sent to patients with radiation rectal injury managed by the committee through the WeChat group. Observational indicators: (1) radiation rectal injury symptom assessment: using SOMA self-rating scale, radiation rectal injury symptom classification: mild group (≤3 points), moderate group (4-6 points) and severe group (> 6 points); (2) incidence of anxiety, depression and physical disorder: using GAD-7, PHQ-9 and PHQ-15 self-rating scales respectively for assessment; (3) correlation of radiation rectal injury symptom grading with anxiety, depression, and somatic symptom disorder. Results: Seventy-one qualified questionnaires were collected, of which 41 (56.9%) were from Guangzhou. Among the 71 patients, 6 were males and 65 were females; the mean age was (55.7±9.3) years old and 48 patients (67.6%) were less than 60 years old; the median confirmed duration of radiation rectal injury was 2.0 (1.0, 5.0) years. (1) Evaluation of symptoms of radiation rectal injury: 18 cases of mild (25.4%), 27 cases of moderate (38.0%), and 26 cases of severe (36.6%). (2) Incidence of anxiety, depression and somatic disorder: 12 patients (16.9%) without comorbidities; 59 patients (83.1%) with anxiety, depression, or somatic disorder, of whom 2 patients only had anxiety, 1 patient only had depression, 9 only had somatic disorder, 2 had anxiety plus depression, 4 had anxiety plus somatic disorder, 2 had depression plus somatic disorder, and 40 had all three symptoms. (3) correlation of radiation rectal injury grading with anxiety, depression, and somatic symptom disorder: as compared to patients in mild group and moderate group, those in severe group had higher severity of anxiety and somatic symptom disorder (Z=-2.143, P=0.032; Z=-2.045, P=0.041), while there was no statistically significant difference of depression between mild group and moderate group (Z=-1.176, P=0.240). Pearson correlation analysis revealed that radiation rectal injury symptom score was positively correlated with anxiety (r=0.300, P=0.013), depression (r=0.287, P=0.015) and somatic symptom disorder (r=0.344, P=0.003). Conclusions: The incidence of anxiety, depression, and somatic symptom disorder in patients with radiation rectal injury is extremely high. It is necessary to strengthen the diagnosis and treatment of somatic symptom disorder, so as to alleviate the symptoms of patients with pelvic perineum pain and improve the quality of life.
Aged
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Anxiety
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Cross-Sectional Studies
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Depression
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Female
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Humans
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Male
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Middle Aged
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Quality of Life
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Rectum
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Surveys and Questionnaires
10.Surgical treatment of primary liver cancer:a report of 10 966 cases
Yongxiang XIA ; Feng ZHANG ; Xiangcheng LI ; Lianbao KONG ; Hui ZHANG ; Donghua LI ; Feng CHENG ; Liyong PU ; Chuanyong ZHANG ; Xiaofeng QIAN ; Ping WANG ; Ke WANG ; Zhengshan WU ; Ling LYU ; Jianhua RAO ; Xiaofeng WU ; Aihua YAO ; Wenyu SHAO ; Ye FAN ; Wei YOU ; Xinzheng DAI ; Jianjie QIN ; Menyun LI ; Qin ZHU ; Xuehao WANG
Chinese Journal of Surgery 2021;59(1):6-17
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.

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