Development and validation of a postoperative pulmonary infection prediction model for patients with primary hepatic carcinoma.

BACKGROUND: There are factors that significantly increase the risk of postoperative pulmonary infections in patients with primary hepatic carcinoma (PHC). Previous reports have shown that over 10% of patients with PHC experience postoperative pulmonary infections. Thus, it is crucial to prioritize the prevention and treatment of postoperative pulmonary infections in patients with PHC. AIM: To identify the risk factors for postoperative pulmonary infection in patients with PHC and develop a prediction model to aid in postoperative management. METHODS: We retrospectively collected data from 505 patients who underwent hepatobiliary surgery between January 2015 and February 2023 in the Department of Hepatobiliary and Pancreaticospleen Surgery. Radiomics data were selected for statistical analysis, and clinical pathological parameters and imaging data were included in the screening database as candidate predictive variables. We then developed a pulmonary infection prediction model using three different models: An artificial neural network model; a random forest model; and a generalized linear regression model. Finally, we evaluated the accuracy and robustness of the prediction model using the receiver operating characteristic curve and decision curve analyses. RESULTS: Among the 505 patients, 86 developed a postoperative pulmonary infection, resulting in an incidence rate of 17.03%. Based on the gray-level co-occurrence matrix, we identified 14 categories of radiomic data for variable screening of pulmonary infection prediction models. Among these, energy, contrast, the sum of squares (SOS), the inverse difference (IND), mean sum (MES), sum variance (SUV), sum entropy (SUE), and entropy were independent risk factors for pulmonary infection after hepatectomy and were listed as candidate variables of machine learning prediction models. The random forest model algorithm, in combination with IND, SOS, MES, SUE, SUV, and entropy, demonstrated the highest prediction efficiency in both the training and internal verification sets, with areas under the curve of 0.823 and 0.801 and a 95% confidence interval of 0.766-0.880 and 0.744-0.858, respectively. The other two types of prediction models had prediction efficiencies between areas under the curve of 0.734 and 0.815 and 95% confidence intervals of 0.677-0.791 and 0.766-0.864, respectively. CONCLUSION: Postoperative pulmonary infection in patients undergoing hepatectomy may be related to risk factors such as IND, SOS, MES, SUE, SUV, energy, and entropy. The prediction model in this study based on diffusion-weighted images, especially the random forest model algorithm, can better predict and estimate the risk of pulmonary infection in patients undergoing hepatectomy, providing valuable guidance for postoperative management.

IL-8-induced CXCR2 down-regulation in circulating monocytes in hepatocellular carcinoma is partially dependent on MAGL.

BACKGROUND: CXC-chemokine receptor 2 (CXCR2) expression was found to be down-regulated on circulating monocytes of cancer patients. Here, we analyze the percentage of CD14+CXCR2+ monocyte subsets in hepatocellular carcinoma (HCC) patients, and investigate the mechanisms that regulate CXCR2 surface expression on monocytes and its biological function. METHODS: Flow cytometry was used to analyze the proportion of the CD14+CXCR2+ subset from the total circulating monocytes of HCC patients. Interleukin 8 (IL-8) levels were measured from serum and ascites, and their correlation with the CD14+CXCR2+ monocyte subset proportion was calculated. THP-1 cells were cultured in vitro and treated with recombinant human IL-8 and CXCR2 surface expression was analyzed. CXCR2 was knocked down to examine how it affects the antitumor activity of monocytes. Finally, a monoacylglycerol lipase (MAGL) inhibitor was added to analyze its effect on CXCR2 expression. RESULTS: A decrease in the proportion of the CD14+CXCR2+ monocyte subset was observed in HCC patients compared with healthy controls. CXCR2+ monocyte subset proportion was associated with the AFP value, TNM stage, and liver function. Overexpression of IL-8 was observed in the serum and ascites of HCC patients, and negatively correlated with CXCR2+ monocyte proportion. IL-8 decreased CXCR2 expression in THP-1 cells, contributing to decreased antitumor activity toward HCC cells. MAGL expression in THP-1 cells was up-regulated after IL-8 treatment, and the MAGL inhibitor partially reversed the effects of IL-8 on CXCR2 expression. CONCLUSIONS: Overexpression of IL-8 drives CXCR2 down-regulation on circulating monocytes of HCC patients, which could be partially reversed by a MAGL inhibitor.

Influencing factors and predictive model of postoperative infection in patients with primary hepatic carcinoma.

BACKGROUND: The purpose of this study was to explore the risk factors for postoperative infection in patients with primary hepatic carcinoma (PHC), build a nomogram prediction model, and verify the model to provide a better reference for disease prevention, diagnosis and treatment. METHODS: This single-center study included 555 patients who underwent hepatobiliary surgery in the Department of Hepatobiliary Surgery of Tianjin Third Central Hospital from January 2014 to December 2021, and 32 clinical indicators were selected for statistical analysis. In this study, Lasso logistic regression was used to determine the risk factors for infection after liver cancer resection, establish a predictive model, and construct a visual nomogram. The consistency index (C-index), calibration curve, and receiver operating characteristic (ROC) curve were used for internal validation, and decision curve analysis (DCA) was used to analyze the clinical applicability of the predictive model. The bootstrap method was used for intramodel validation, and the C-index was calculated to assess the model discrimination. RESULTS: Among the 555 patients, 279 patients met the inclusion criteria, of whom 48 had a postoperative infection, with an incidence rate of 17.2%. Body mass index (BMI) (P = 0.022), alpha-fetoprotein (P = 0.023), total bilirubin (P = 0.016), intraoperative blood loss (P < 0.001), and bile leakage (P < 0.001) were independent risk factors for infection after liver cancer surgery. The nomogram was constructed and verified to have good discriminative and predictive ability. DCA showed that the model had good clinical applicability. The C-index value verified internally by the bootstrap method results was 0.818. CONCLUSION: Postoperative infection in patients undergoing hepatectomy may be related to risk factors such as BMI, preoperative AFP level, TBIL level, intraoperative blood loss and bile leakage. The prediction model of the postoperative infection nomogram established in this study can better predict and estimate the risk of postoperative infection in patients undergoing hepatectomy.

Diagnostic efficacy of contrast-enhanced ultrasound, dynamic contrast-enhanced MRI combined with tumor markers AFP and DCP for primary hepatocellular carcinoma.

The purpose of this study was to investigate the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined with tumor markers alpha-fetoprotein (AFP) and des-γ-carboxyl prothrombin (DCP) for primary hepatic carcinoma (PHC). A total of 70 patients with PHC (PHC group), 42 patients with liver cyst (benign liver disease group (BLDG)) and 30 healthy people (healthy group (HG)) were selected as the research objects. CEUS and DCE-MRI were performed by American GE Vivid E9 color Doppler ultrasound system and Siemens 1.5T magnetic resonance imager, respectively. The levels of AFP and DCP were detected by ABBOTT i2000SR chemiluminescence instrument and enzyme-linked immunoassay (ELISA), respectively. In DCE-MRI examination, the portal phase and prolonged phase were mostly low signal in T1-weighted imaging (T1WI) sequence, and arterial phase was mostly high signal in T2WI sequence. In CEUS, most lesions showed hyper-enhancement in arterial phase, and hypo-enhancement in portal phase and delayed phase. AFP and DCP levels in PHC group were significantly higher than that in BLDG group and HG group. There were statistically significant differences among the three groups. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of combined diagnosis were statistically significant when compared with CEUS, AFP and DCP alone and either AFP or DCP positive. CEUS, DCE-MRI combined with tumor markers AFP and DCP have high sensitivity, specificity and accuracy in the diagnosis of PHC, which can more accurately diagnose the lesion type, provide basis for further treatment, and is worthy of clinical application.

Effects of Jianpi Huaji Fuzheng Decoction supplemented with conventional chemotherapy on cellular immunity and coagulation-fibrinolysis function in patients with primary hepatic carcinoma of spleen-deficiency syndrome / 国际中医中药杂志

Objective:To explore the effects of Jianpi Huaji Fuzheng Decoction supplemented with conventional chemotherapy on Traditional Chinese Medicine (TCM) syndromes scores, cellular immunity and coagulation-fibrinolysis function in patients with primary hepatic carcinoma of spleen-deficiency syndrome.Methods:Prospective cohort study. A total of 85 patients with primary hepatic carcinoma of spleen-deficiency syndrome who met the inclusion criteria in the hospital between March 2018 and March 2021 were divided into 42 cases in control group and 43 cases in observation group according to the random number table method. The control group was given conventional western medicine chemotherapy, and the observation group was given Jianpi Huaji Fuzheng Decoction on the basis of the control group. Both groups were treated for 3 months. Before and after treatment, the TCM syndromes were scored. The levels of CD4 + and CD8 + were detected by flow cytometry with indirect immunofluorescence, and the ratio of CD4 +/CD8 + was calculated. The plasma prothrombin time (PT), fibrinogen (Fg) and coagulation factor Ⅶ (CFⅦ) were detected by automatic blood coagulation analyzer. The toxic and side effects of chemotherapy during treatment were recorded and the clinical efficacy was evaluated. Results:The total effective rate of syndrome efficacy was 95.35% (41/43) in observation group and 78.57% (33/42) in control group ( χ2=3.92, P=0.047). After treatment, the scores of flank pain, lumps, fatigue and jaundice and total score in observation group were significantly lower than those in the control group ( t=2.60, 2.64, 2.85, 2.91, 3.79, P<0.01). The level of CD4 + [(37.68±3.72)% vs. (35.92±3.61)%, t=2.21] and CD4 +/CD8 + [(1.44±0.22) vs. (1.31±0.23), t=2.66] in observation group were significantly higher than those in the control group ( P<0.05), while the level of CD8 + [(26.20±2.72)% vs. (27.44±2.16)%, t=2.32] was significantly lower than that of the control group ( P<0.05). The levels of Fg [(3.11±0.85) g/L vs. (2.74±0.72) g/L, t=2.16] and CFⅦ [(1.76±0.44) mg/L vs. (1.58±0.37) mg/L, t=2.04] were significantly higher than those in the control group ( P<0.05). PT [(14.65±2.72) s vs. (15.91±3.03) s, t=2.02] was significantly shorter than that of the control group ( P<0.05). During treatment, the incidence rate of toxic and side effects of chemotherapy was 11.63% (5/43) in observation group and that in control group was 30.95% (13/42) ( χ2=4.75, P=0.029). Conclusion:Jianpi Huaji Fuzheng Decoction supplemented with conventional chemotherapy can improve the clinical symptoms, promote the recovery of cellular immune function and coagulation-fibrinolysis function, reduce the incidence rates of toxic and side effects of chemotherapy, and enhance the clinical efficacy of patients with primary hepatic carcinoma.

Percutaneous microwave ablation and transcatheter arterial chemoembolization for serum tumor markers and prognostics of middle-late primary hepatic carcinoma.

BACKGROUND: Primary hepatic carcinoma (PHC) has an insidious onset and is usually diagnosed in the middle and late stages. Although transcatheter arterial chemoembolization (TACE) is the preferred option for treating middle- and advanced-stage PHC, it has limited efficacy in killing tumor cells and poor long-term efficacy. TACE plus percutaneous microwave coagulation therapy (PMCT) is more effective than interventional therapy alone and can improve survival time. However, there are few reports on the effects of TACE and PMCT on serum marker levels and the prognosis of patients with advanced PHC. AIM: To investigate the effect of PMCT + TACE on serum tumor markers and the prognosis of middle-late PHC. METHODS: This retrospective study included 150 patients with middle-late PHC admitted to Zhongshan People's Hospital between March 2018 and February 2021. Patients were divided into a single group (treated with TACE, n = 75) and a combined group (treated with TACE + PMCT, n = 75). Before and after treatment, the clinical efficacy and serum tumor marker levels [carbohydrate antigen 19-9 (CA19-9), alpha-fetoprotein (AFP), and carcinoembryonic antigen (CEA)] of both groups were observed. The 1-year survival rates and prognostic factors of the two groups were analyzed. RESULTS: The combined group had 21 and 35 cases of complete remission (CR) and partial remission (PR), respectively. The single group had 13 and 25 cases of CR and PR, respectively. After 4 wk of treatment, the serum CA19-9, CEA, and AFP levels in the single and combined groups decreased, with the decrease in the combined group being more significant (P < 0.05). The 1-year survival rate of the combined group (80.00%) was higher than that of the single group (60.00%) (P < 0.05). The average survival time within 1 year in the combined group was 299.38 ± 61.13 d, longer than that in the single group (214.41 ± 72.97 d, P < 0.05). COX analysis revealed that tumor diameter, tumor number, and the treatment method were prognostic factors for patients with middle-late PHC (P < 0.05). CONCLUSION: TACE + PMCT is effective in treating patients with mid-late PHC. It reduces the levels of tumor markers, prolongs survival, and improves prognosis.

[Progress and application of liver organoids in the study of liver cancer].

The incidence rate of liver cancer has been rising in recent years. Traditional cell line culture and human patient-derived tumor xenograft models, which are commonly used tools to simulate the occurrence of human liver cancer, have deepened the understanding of tumor occurrence, development, and drug resistance mechanisms. However, they cannot reflect the accurate state of cancer cells, the tumor microenvironment, or spatial structural characteristics. Recently, more in vitro-produced physiological liver organoids have been applied in the study of liver cancer. Liver organoid models have made breakthroughs in the occurrence and development mechanisms of liver cancer, personalized drug screening and biomarker identification, immunotherapy, and regenerative medicine applications. This paper mainly summarizes the progress and application of liver organoids processed in the study of liver cancer.

Construction and validation of a prediction model of extrahepatic metastasis for hepatocellular carcinoma based on common clinically available data.

Objective: This study aimed to investigate the clinical characteristics and risk factors of patients with hepatocellular carcinoma (HCC) with extrahepatic metastases (EHM) and to establish an effective predictive nomogram. Methods: Clinical and pathological data from 607 patients with hepatocellular carcinoma admitted to the Affiliated Hospital of Qinghai University between 1 January 2015 and 31 May 2018 were documented, as well as demographics, clinical pathological characteristics, and tumor-related parameters to clarify clinical risk factors for HCC EHM. These risks were selected to build an R-based clinical prediction model. The predictive accuracy and discriminating ability of the model were determined by the concordance index (C-index) and the calibration curve. The results were validated with a bootstrap resample and 151 patients from 1 June 2018 to 31 December 2019 at the same facility. Results: In multivariate analysis, independent factors for EHM were neutrophils, prothrombin time, tumor number, and size, all of which were selected in the model. The C-index in the EHM prediction model was 0.672 and in the validation cohort was 0.694. In the training cohort and the validation cohort, the calibration curve for the probability of EHM showed good agreement between the nomogram prediction and the actual observation. Conclusion: The extrahepatic metastasis prediction model of hepatocellular carcinoma constructed in this study has some evaluation capability.

Tertiary Lymphatic Structures in Primary Hepatic Carcinoma: Controversy Cannot Overshadow Hope.

Tertiary lymphoid structures (TLSs) are organized aggregates of immune cells found in the tumor microenvironment. TLS can influence primary hepatic carcinoma (PHC) occurrence and have an active role in cancer. TLS can promote or inhibit the growth of PHC depending on their location, and although available findings are controversial, they suggest that TLS have a protective role in PHC tissues and a non-protective role in paracancerous tissues. In addition, the cellular composition of TLS can also influence the outcome of PHC. As an immunity marker, TLS can act as a marker of immunotherapy to predict its effect and help to identify patients who will respond well to immunotherapy. Modulation of TLS formation through the use of chemokines/cytokines, immunotherapy, or induction of high endothelial vein to interfere with tumor growth has been studied extensively in PHC and other cancers. In addition, new tools such as genetic interventions, cellular crosstalk, preoperative radiotherapy, and advances in materials science have been shown to influence the prognosis of malignant tumors by modulating TLS production. These can also be used to develop PHC treatment.

Aptamer-Based Triple Serum Fluorescence Intensity Assay: A Novel and Feasible Method for the Clinical Diagnosis of Primary Hepatic Carcinoma.

Background and Aims: Aptamers are artificial ligands that bind to biological targets with high specificity and affinity. We previously selected a group of aptamers against the serum of primary hepatic carcinoma (PHC) via systematic evolution of ligands by exponential and enrichment (SELEX) method, and some of the aptamers were valuable for PHC diagnosis in polyacrylamide gel electrophoresis (PAGE) analysis. Here, we used aptamers to develop a novel method suitable for the clinical diagnosis of PHC. Methods: The intensities of serum autofluorescence, cell-free DNA (cfDNA)-related fluorescence and aptamer-related fluorescence, named the aptamer-based triple serum fluorescence intensity (ATSFI), were sequentially measured at 8 °C and 37 °C in one tube by using a real-time polymerase chain reaction (PCR) system as a fluorimeter in patients with PHC (n=346) or liver cirrhosis (n=321). The diagnostic performances of ATSFI indicators alone and in combination were evaluated by area under the receiver operator characteristic curve (AUROC), and the underlying clinical mechanisms were analyzed by bivariate correlation. Results: The measurement of ATSFI was high throughput, rapid, convenient, and low cost. The aptamer-related fluorescence indicator SEA-SE37 was the most valuable for PHC diagnosis among all fluorescence indicators and superior to alpha-fetoprotein (AFP) (AUROC 0.879 vs. 0.836). The logistic model of ATSFI indicators exhibited excellent diagnostic performance for PHC, including AFP-negative, early and small PHCs, with AUROCs of 0.935-0.950 and accuracies of 86.8-88.3%. The diagnostic performance was further improved when ATSFI indicators were combined with AFP, with AUROCs of approximately 0.95 and accuracies of approximately 90%, suggesting ATSFI was independent of but complementary to AFP in PHC diagnosis. ATSFI models were highly valuable in clinical decision-making. The aptamer-related fluorescence intensity was generally independent of the clinicopathological characteristics of PHC but correlated with laboratory characteristics of PHC serum. Conclusions: The ATSFI assay is a novel, robust and feasible method for the clinical diagnosis of PHC.

Mechanism of Cordycepin Inhibiting Proliferation and Promoting Apoptosis of Hepatoma Cells by Regulating Gli1 / 中国实验方剂学杂志

ObjectiveTo investigate the molecular mechanism of cordycepin inhibiting proliferation and promoting apoptosis of human hepatoma cells （HCCs）. MethodGlioma-associated oncogene homolog 1 （Gli1） gene was silenced by small interfering RNA （siRNA） and transfected into SMMC-7721 cells， and then cell proliferation was detected by cell counting kit-8 （CCK-8） assay and cell cloning assay. SMMC-7721 cells were treated with different concentration of cordycepin， and the cell proliferation and apoptosis were examined. The expression of Gli1 and the downstream related genes was determined by Real-time polymerase chain reaction（PCR） and Western blot. ResultThe mRNA and protein expression of Gli1 in SMMC-7721 cells was higher than that in normal liver cells （P<0.01）. The proliferation rate of SMMC-7721 with silenced Gli1 decreased at 72 and 96 h （P<0.05， P<0.01）， and the colony-forming capacity lowered （P<0.01） compared with those in the blank group. Compared with the control， 80 μmol·L-1 and 120 μmol·L-1 cordycepin significantly inhibited the proliferation of SMMC-7721 cells at 72 and 96 h （P<0.05， P<0.01）， and promoted the apoptosis of them （P<0.01）. Moreover， 80 and 120 μmol·L-1 cordycepin restrained the mRNA and protein expression of Gli1 in SMMC7721 cells （P<0.05， P<0.01）. At 120 μmol·L-1， cordycepin led to the decrease in the mRNA and protein levels of B-cell lymphoma-2 （Bcl-2） and c-Myc （P<0.05， P<0.01）， and the increase in the mRNA and protein expression of cysteine-aspartic acid protease-3 （Caspase-3） （P<0.05）. ConclusionGli1 is highly expressed in HCCs， and cordycepin can suppress the proliferation and enhance the apoptosis of HCCs by regulating Gli1 and the downstream apoptosis-related factors.

The value of serum TK1 and MMP-9 level in prognosis evaluation of primary hepatic carcinoma / 中国医师杂志

Objective:To investigate the value of serum thymidine kinase-1 (TK1) and matrix metalloproteinase-9 (MMP-9) level in prognosis evaluation of patients with primary hepatic carcinoma (PHC).Methods:100 PHC patients treated in Panjin Central Hospital from December 2015 to December 2017 were retrospectively selected and divided into survival group ( n=73) and death group ( n=27) according to the prognosis. The clinical characteristics and serum TK1 and MMP-9 levels of the two groups were compared. The relationship between serum TK1 and MMP-9 levels and the clinical characteristics and prognosis of PHC was analyzed. Receiver operating characteristic (ROC) curve was drawn to analyze the value of TK1 and MMP-9 in evaluating the prognosis of PHC. Results:The proportion of multiple lesions, low differentiation, tumor node metastasis (TNM) stage Ⅲ-Ⅳ, extrahepatic metastasis and microvascular invasion in the survival group were lower than those in the death group, and the levels of serum TK1 and MMP-9 were also lower than those in the death group (all P<0.05); The levels of serum TK1 and MMP-9 had no significant correlation with gender, age, tumor length and diameter and child Pugh liver function grade of PHC patients (all P>0.05), but were closely related to the number of lesions, degree of differentiation, TNM stage, extrahepatic metastasis and microvascular invasion (all P<0.05). The areas under the ROC curve of serum TK1 and MMP-9 levels predicting the prognosis of PHC were 0.859 and 0.830. The 3-year survival rate of PHC patients with high level of TK1 and MMP-9 was significantly lower than that of low level patients (all P<0.05). Conclusions:The serum TK1 and MMP-9 levels are correlated with the condition and prognosis of patients with PHC, and can be used as reference indexes for early prognosis evaluation.

Efficacy Evaluation on the Color Doppler Ultrasound, Multislice Spiral CT Combined with Serum Markers in Diagnosis of Primary Hepatic Carcinoma.

BACKGROUND: The efficacy of color Doppler ultrasound, multislice spiral CT combined with serum alpha-fetoprotein (AFP) and alpha-fetoprotein heterogeneity (AFP-L3) in the diagnosis of primary hepatic carcinoma was evaluated. METHODS: Seventy-nine patients with primary hepatic carcinoma (PHC group) and 50 patients with benign liver lesions (benign control group) admitted in Yantaishan Hospital (Yantai, China) from January 2016 to December 2018 were selected. The liver was scanned by color Doppler ultrasound and multiple multislice spiral CT. The serum AFP and AFP-L3 levels were detected by electrochemiluminescence. The value of color Doppler ultrasound, multislice spiral CT combined with serum AFP and AFP-L3 in diagnosis of primary liver cancer was retrospectively analyzed. RESULTS: The color Doppler flow imaging (CDFI) showed a high-speed and high-resistance spectrum. The serum AFP and AFP-L3 levels of patients with primary hepatic carcinoma were significantly higher than those of the benign control group were (U=138.000 and 155.500, P=0.000 and 0.000), P<0.01. The sensitivity, accuracy and negative predictive value of color Doppler ultrasound, multislice spiral CT combined with serum AFP and AFP-L3 examinations for diagnosis of primary hepatic carcinoma were 96.20, 90.70 and 93.18%, which was significantly improved compared with each single examination (X2=27.888, 17.511 and 16.202, P=0.000, 0.002 and 0.003), P<0.01. CONCLUSION: Color Doppler ultrasound, multislice spiral CT combined with AFP and AFP-L3 examination could significantly improve the diagnosis efficiency of primary hepatic carcinoma, which was beneficial to early clinical diagnosis and early treatment.

Primary hepatic carcinoma with inhibin positivity in a young male patient: a rare tumor previously only reported in females-case report and review of literature.

Primary hepatic carcinoma with inhibin positivity is a rare aggressive liver tumor with seven cases described. The tumor presents at a younger age than primary hepatic carcinoma with all cases being females. RNA albumin ISH positivity suggests the tumor to be a primary hepatic carcinoma. The tumor is different from hepatocellular carcinoma as well as intrahepatic cholangiocarcinoma because of its distinct morphology, lack of hepatocellular differentiation, strong inhibin staining, and lack of typical mutations. A 26-year-old male presented with a 20-cm liver mass. The tumor progressed on therapy with development of multiple lung metastasis. Currently, the patient is enrolled in phase II clinical trial utilizing nivolumab and ipilumumab. While the tumor has a female preponderance, it is not exclusively found in females. Additional studies are necessary to determine the cause of inhibin staining, driving molecular alterations, natural history of this rare tumor, and to come up with consensus nomenclature.

Meta-analysis and Trial Sequential Analysis of Effectiveness and Safe ty of Compound Banmao Capsules Combined with Different Chemoradiotherapy in the Treatment of Primary Hepatic Carcinoma / 中国药房

OBJECTIVE：To systematically evaluate th e efficacy and safety of Compound banmao capsules combined with different chemoradiotherapy in the treatment of primary hepatic carcinoma （PHC）. METHODS ：Retrieved from CBM ，CNKI， Wanfang database ，VIP，PubMed，Embase and Cochrane Library during the inception to Sept. 2020，randomized controlled trial （RCTs），cohort study about Compound banmao capsules combined with different chemoradiotherapy plans （trial group ）versus different chemoradiotherapy plans （control group ）were collected. After literature screening and data extraction ，the quality of included RCTs were evaluated with bias risk evaluation tool recommended by Cochrane system evaluator mannual 5.1.0. Newcastle Ottawa scale was used to evaluate the quality of cohort 502） studies；Rev Man 5.3 software was used for Meta-analysis ；TSA 0.9.5.10 Beta software was used for trail sequential analysis，and GRADE Profiler 3.6.1 software was used for evidence quality evaluation of RCT and cohort studies . RESULTS：A total of 15 RCTs were included ，involving com 1 148 patients. Meta-analysis showed that effective rate of trial group was significantly higher than that of control group [RR ＝0.80，95％CI（0.73，0.88），P＜0.000 01]. The results of subgroup analysis according to different chemotherapy plan showed that the effective rate of trial group combined with TACE and three dimensional conformal radiotherapy were significantly higher than control group （P＜0.05）. The survival rate of trial group was significantly higher than control group [RR ＝0.81，95％CI（0.74，0.89），P＜0.000 1]；the results of subgroup analysis according to different survival time showed that 1-year，2-year and 3-year survival rates of trial group were significantly higher than control group（P＜0.05）. The incidence of myelosuppression in trial group was significantly lower than control group ，and the natural killer cell count and T cell count of trial group were significantly higher than control group （P＜0.05）. There was no statistical significance in AFP content and liver function index between 2 groups（P＞0.05）. Trial sequential analysis showed that there was definite evidence for better effective rate of Compound banmao capsules combined with TACE. GRADE evaluation results showed that the evidence level of effective rate was intermediate ，the evidence level of survival rate and incidence of myelosuppression was low，and other indicators were very low. CONCLUSIONS ：Compound banmao capsules combined with different chemoradiotherapy in the treatment of PHC has significant efficacy and good safety ，especially in combination with TACE ，and the evidence level of effective rate is intermediate.

The analysis of the change characteristics of PET/CT metabolic parameters before and after liver transplantation for liver cancer / 中华器官移植杂志

Objective:The aim of this study was to analyze the relationship between the changes of pre- and post-operation PET/CT metabolic parameters and prognosis for liver cancer patients.Methods:A retrospective study was carried out among 92 patients with liver cancer who received liver transplantation and PET/CT examination in our hospital from October 2013 to May 2017.According to Deauville criteria, the lesions were classified into PET negative, weak positive, and strong positive. The metabolic parameters including SUV max, SUL, MTV, TMR, TLR, TLG, UVP of normal liver parenchyma, liver cancer lesions and mediastinum were measured or calculated. The relationship between metabolic parameters and recurrence was analyzed. The relationship of Deauville score and metabolic parameters and the changing characters of metabolic parameters between the PET/CT of pre and post transplantation were analyzed. Results:Thirty cases did not relapse after LT, among which 16, 7 and 7 cases had Deauville score of 3, 4 and 5 respectively in pre-operation PET/CT. The recurrence time of 62 patients in recurrence group was (10.90±10.30) months. MTV, TLG, UVP-M, UVP-LB in recurrence group were significant higher( P<0.05). Patients with low metabolic parameters show better prognosis than patients with high metabolic parameters. Metabolic parameters of 5 score group were higher than that of 4score. The metabolic parameters of recurrence group were higher than those in non-recurrence group. MTV, TLG, UVP-M, UVP-LB in post-operation PET/CT were lower than those in pre-operation PET/CT, however, SUV max, TMR, TLR, SUL had no significantly difference. Conclusions:PET/CT metabolic burden parameters should be evaluated before LT to select patients with better prognosis. For liver transplantation patients with high metabolic parameters, PET/CT examination should be performed early after surgery to improve the detection of recurrence and metastasis, and relevant treatment should be timely conducted.

Meta-analysis of Oral Chinese Medicine for Adjuvant Treatment of Primary Hepatic Carcinoma and Screening of Basic Chinese Herbs / 中国实验方剂学杂志

Objective:To systematically evaluate the efficacy of oral Chinese herbal prescriptions combined with transcatheter arterial chemoembolization （TACE） against primary hepatic carcinoma （PHC） and screen the basic Chinese herbs，in order to provide certain reference for clinical medication. Method:The randomized controlled trials concerning the treatment of PHC with oral Chinese herbal prescriptions plus TACE were retrieved from CBM，China National Knowledge Infrastructure （CNKI），Chongqing Weipu Database for Chinese Technical Periodicals （VIP），and Wanfang Data Knowledge Service Platform.The quality of the included trials was evaluated by Cochrane handbook，and the Meta-analysis was performed using RevMan 5.3.The enumeration data were expressed by odds ratio （OR），the measurement data by mean difference （MD） or standardized mean difference （SMD），and the effect size by 95% confidence interval （CI）.The data of oral Chinese herbal prescriptions involved in trials were sorted out and subjected to association rule analysis and frequency analysis based on the Traditional Chinese Medicine Inheritance Support System （TCMISS），for exploring the basic Chinese herbs and their dosages against PHC. Result:A total of 75 randomized controlled trials were included，involving 7 406 cases. As revealed by the Meta-analysis，oral Chinese herbal prescriptions combined with TACE was significantly better than TACE alone in improving the short-term curative effect ［OR=2.05，95%CI（1.83，2.29）］，decreasing alpha fetoprotein （AFP） ［MD=-59.02，95%CI（-79.03，-39.01）］，ameliorating liver function ［SMD=-1.23，95%CI（-1.58，-0.88）］，boosting immunity ［SMD=1.08，95%CI（0.84，1.32）］，adjusting Karnofsky Performance Status （KPS） scale score ［OR=2.7，95%CI（1.11，11.02）］，elevating survival rate ［OR=2.31，95%CI（1.96，2.71）］，and reducing adverse reactions ［OR=0.38，95%CI（0.34，0.43）］.Data mining results showed that the basic Chinese herbs against PHC were Bupleuri Radix，Paeoniae Alba Radix，Atractylodis Macrocephalae Rhizoma，Poria，and Glycyrrhizae Radix et Rhizoma，with their clinical dosages listed as follows：6-15 g for Bupleuri Radix，10-15 g for Paeoniae Alba Radix，9-15 g for Atractylodis Macrocephalae Rhizoma，10-15 g for Poria，and 3-10 g for Glycyrrhizae Radix et Rhizoma. Conclusion:The oral Chinese herbal prescriptions combined with TACE produce better effects in treatment of PHC as compared with TACE alone.These five basic Chinese herbs have anti-cancer effect，and their dosages are within the ranges stipulated in 2020 edition of <italic>Chinese Pharmacopoeia.</italic>This Meta-analysis has provided certain reference for clinical medication.

Serum Tumor Markers for Early Diagnosis of Primary Hepatocellular Carcinoma.

Primary hepatocellular carcinoma (HCC) is one of the most frequently occurring pernicious tumors in the world. It is typically very insidious in the early stages with no obvious symptoms. Its development and metastasis are very rapid. Upon diagnosis, most patients have already reached a local advanced stage or have established distant metastases. The treatment of HCC is limited, with poor prognosis and short natural survival time. In order to improve the efficiency of early diagnosis, it is particularly significant to choose economic and effective diagnosis methods. Ultrasound, magnetic resonance imaging, and computed tomography are usually used in the clinic, but these methods are extremely limited in the diagnosis of HCC. Tumor markers have become the main effective early clinical diagnosis method. Potential serum tumor markers include alpha fetoprotein heterogeneity, Golgi protein 73, phosphatidylinositol proteoglycan (GPC-3), osteopontin, abnormal prothrombin, and heat shock protein. These tumor markers provide new ideas and methods for the diagnosis of HCC. A combination of multiple markers can make up for the deficiency of single marker detection and provide a new strategy for the prognosis and auxiliary diagnosis of HCC. This review introduces protein tumor markers utilized over the past five years.

[Analysis of clinical efficacy, safety and prognosis of anlotinib hydrochloride in the treatment of advanced primary liver cancer].

Objective: To retrospectively analyze the clinical efficacy, safety and the main factors affecting the prognosis of anlotinib hydrochloride in the treatment of advanced primary liver cancer. Methods: Fifty-five cases with advanced primary liver cancer who received anlotinib hydrochloride were enrolled. The baseline data of the patients, such as prothrombin time, total bilirubin, albumin, Child-Pugh score, procalcitonin, alpha fetoprotein, extrahepatic metastasis, cirrhosis, portal hypertension, whether or not combined surgery, pathological staging, etc before treatment were recorded. Hematological and imaging results of the patients were reviewed. Adverse events that appeared in patients at any time until the end of follow-up or loss- to- follow-up or death were recorded. The survival curve was plotted by Kaplan-Meier method, and the difference of survival time between groups was examined by log-rank test. Cox regression model of single and multiple factor were used to analyze the factors affecting the prognosis. Results: As of the last follow-up, 2 patients were lost-to-follow-up, 30 died, and 23 survived. The median survival time was 6.5 months (196 days). Grade 3 or higher adverse events included hypertension (12.73%), leukopenia (3.64%), absolute neutropenia (1.82%), thrombocytopenia (9.09%), fatigue (3.64%), anemia (1.82%), and diarrhea (1.82%). Adverse events were effectively controlled. One case had fatal ruptured esophageal varices, which were not medically related. Multivariate Cox regression analysis showed that total bilirubin (HR = 0.247, P = 0.003), albumin (HR = 0.279, P = 0.003) and procalcitonin (HR = 0.105, P = 0.012) were independent factors affecting the prognosis of advanced HCC. Conclusion: Anlotinib hydrochloride therapy is safe, effective and well tolerated in patients with advanced liver cancer, and total bilirubin, albumin, and procalcitonin are independent factors that affect the prognosis of patients with advanced liver cancer.

Expression of CD4+CD25+CD127Low regulatory T cells and cytokines in peripheral blood of patients with primary liver carcinoma.

Objective: To assess the clinical utility of the ratio of CD4+CD25+CD127low regulatory T cells (Tregs) in subjects at high risk of HCC, investigate the relationship between the percentage of Tregs and the expression of transforming growth factor (TGF)-ß1 and interleukin (IL)-10 in patients with hepatocellular carcinoma before and after treatment. Methods: Peripheral venous blood was collected from patients with liver cancer before and after treatment. The proportion of CD4+CD25+CD127low Tregs was detected by flow cytometry. The levels of TGF-ß1 and IL-10 in serum were detected by enzyme-linked immunosorbent assay, and were compared with healthy subjects as a control group. Results: The proportion of CD4+CD25+CD127low to CD4+T lymphocytes in patients with hepatocellular carcinoma was significantly higher than that in healthy controls (P<0.01). The proportion of CD4+CD25+CD127lowTregs, whose AUC of ROC curve was 0.917, could effectively separate the HCC patients from the healthy subjects with a diagnostic sensitivity of 90%, specificity of 80%. The proportion of CD4+CD25+CD127low to CD4+T lymphocytes and the levels of TGF-ß1 and IL-10 in patients with hepatocellular carcinoma after the operation and chemotherapy were significantly lower than those before treatment (P<0.05).The proportion of CD4+CD25+CD127lowTregs was positively correlated with the concentrations of TGF-ß1 and IL-10 before and after treatment of primary liver cancer (P<0.05). Conclusion: CD4+CD25+CD127lowTregs may be a significant predictor of HCC biopsy outcome and play an inhibitory role on effector T cells by regulating cytokines.