Objective:To evaluate the effectiveness of enhanced CT texture feature analysis in predicting pseudoprogression in patients with metastatic clear cell renal cell carcinoma (mccRCC) undergoing programmed cell death protein 1 (PD-1) inhibitor therapy.Methods:A cross-sectional study. Data from 32 patients with mccRCC were retrospectively collected who received monotherapy with PD-1 inhibitors after standard treatment failure at Henan Cancer Hospital, from June 2015 to January 2021. Clinical information and enhanced CT images were analyzed to assess target lesion response. The lesions were divided into pseudoprogression and non-pseudoprogression groups. Manual segmentation of target lesions was performed using ITK-Snap software on baseline enhanced CT, and texture analysis was conducted using A.K. software to extract feature parameters. Differences in texture features between the pseudoprogression and non-pseudoprogression groups were analyzed using univariate and multivariate logistic regression. A predictive model for pseudoprogression was constructed, and its performance was evaluated using ROC curve analysis.Results:A total of 32 patients with 89 lesions were included in the study. Statistical analysis revealed significant differences in seven texture features between the pseudoprogression and non-pseudoprogression groups. These features included“original_ngtdm_Strength”(0.49 vs. -0.61, P=0.006), “wavelet-HLH_glszm_ZonePercentage”(0.67 vs. -0.22, P=0.024),“wavelet-LHL_ngtdm_Strength”(1.20 vs. -0.51, P=0.002), “wavelet-HLL_gldm_LargeDependenceEmphasis”(-0.84 vs. 0.19, P=0.002), “wavelet-HLH_glcm_Id” (-0.30 vs. 0.43, P=0.037),“wavelet- HLH_glrlm_RunPercentage”(0.45 vs. -0.01, P=0.032),“wavelet-LHH_firstorder_Skewness”(0.25 vs. -0.27, P=0.011). Based on these features, a pseudoprogression prediction model was developed with a P-value of 0.000 2 and an odds ratio of 0.045 (95% CI 0.009-0.227). The model exhibited a high predictive performance with an AUC of 0.907 (95% CI 0.817-0.997) according to ROC curve analysis. Conclusions:Enhanced CT texture feature analysis shows promise in predicting lesion pseudoprogression in patients with metastatic ccRCC undergoing PD-1 inhibitor therapy. The developed predictive model based on texture features demonstrates good performance and may assist in evaluating treatment response in these patients.

[摘 要] 目的：通过对比免疫相关不良反应（irAE）发生前后血常规中主要指标的变化，为鉴别诊断irAE及感染性炎症提供新依据。方法：回顾性分析201例2018年8月至2022年6月在河南省肿瘤医院接受抗PD-1抗体治疗后出现irAE的肿瘤患者的临床资料，包括抗PD-1抗体治疗前、发生irAE前及irAE后血常规的主要指标，采用配对t检验分析治疗前后血常规指标值的统计学差异。采用定性变量的配对c2检验分析治疗前后血常规指标值的阳性率（高于正常值的比例）的统计学差异。结果：从201例患者中观察到了258次irAE，其中27例（13.4%）患者发生了2种及以上类型的irAE，214次（82.94%）irAE未引起发热；irAE发生后与抗PD-1抗体治疗前相比，白细胞计数（t=1.087, P=0.278）、中性粒细胞计数（t=0.959, P=0.338）及中性粒细胞百分比（t=0.817，P=0.414）未见明显升高，且三指标高于正常值的病例数分别为28 vs 38（χ2=1.737，P=0.187）、32 vs 44（χ2=2.222，P=0.136）、45 vs 55（χ2=1.240，P=0.265）,差异均无统计学意义。结论：irAE发生后患者外周血白细胞计数、中性粒细胞计数及中性粒细胞百分比无明显变化，这对鉴别诊断感染性炎症可能具有参考意义。

Objective To explore the efficacy, safety, and factors that might influence the efficacy of antiPD-1 antibody-based therapy in advanced hepatocellular carcinoma in the real world. Methods The clinical features, efficacy, and safety in patients with advanced hepatocellular carcinoma who received anti-PD-1 antibody-based therapy were retrospectively analyzed. The survival status was followed-up. Results The objective response and the disease control rate were 21.8% and 76.4%, respectively. The overall incidence of adverse events during treatment was 81.8%, of which the incidence of grade 3/4 adverse events was 14.5%. The incidence of immune-related adverse events was 58.2% and the incidence of grade 3/4 immune-related adverse events was 3.6%, and no treatment-related death was observed. The median PFS of the 55 patients was 5.0 (95%CI: 3.9-6.1) months, and the median OS was 11.4 (95%CI: 6.5-16.3) months. Univariate and multivariate analyses showed that liver function Child-Pugh scores and performance status ECOG score were the influencing factors of the objective response rate and survival. Conclusion In the real world anti-PD-1 antibody-based therapy is safe and effective in patients with advanced hepatocellular carcinoma, in which the performance status ECOG score and liver function Child-Pugh score before treatment are independent prognostic factors influencing survival.

Treatment with molecular targeted drugs and immune checkpoint inhibitors (ICIs) has become the first-line treatment options for unresectable HCC (hepatocellular carcinoma) and is also one of the anti-recurrence therapies of choice for patients at high risk of recurrence following radical treatment. First-line molecular targeted drugs combined with ICIs or dual-immune therapy significantly increase the median overall survival and objective response rate compared to single-targeted drugs. Targeted therapy and immunotherapy are suitable for HCC patients with Child-Pugh classes A~B. Liver damage caused by targeted drugs includes abnormal transaminases and bilirubin and, in severe cases, hypoproteinemia, ascites, and other occurrences. ICIs-associated immune-mediated hepatitis (IMH) mostly occurs within one to three sessions of treatment (4~12 weeks) and can be treated with glucocorticoids. However, immunosuppressants such as mycophenolate mofetil may be used as necessary.Targeted drugs and ICIs with different mechanisms of action can be selected based on the systemic condition and tumor treatment needs following the restoration of normal liver function.

Objective:To investigate the ability of the anti-PD-1(scFv)/hIL-15 fusion protein(PD-15) to specifically bind to PD-1 in vitro and the effect of the combination of PD-15 with GF-hIL-15Ra-K562(G15Ra-K562) feeder cells to expand NK/T cells. Methods:Overlap PCR was used to construct G15Ra expression vector. pMXs-G15Ra-IP was transfected into K562 by electroporation. G15Ra-K562 feeder cell lines were obtained by limiting dilution method. pUC57-PD-15 was constructed by digestion and ligation. Lipofectamine? 2000 was used to transiently transfect pUC57-PD-15 into HEK293T cells and the conditioned medium containing PD-15 fusion protein was obtained. Density gradient centrifugation was used to obtain human peripheral blood mononuclear lymphocytes(PBMC), and CFSE staining was used to mark active proliferating cells. Flow cytometry was used to detect the ability of PD-15 to specifically bind to PD-1 and its effect on the proliferation of human PBMC and the proportion of different subpopulations of lymphocytes.Results:The feeder cells G15Ra-K562 with high expression of fusion protein G15Ra was successfully constructed. The addition of hIL-15 can increase the ability of G15Ra-K562 to expand human PBMC by more than 5 times( P<0.05). PD-15 fusion protein has PD-1 specific binding ability( P<0.001), combined with G15Ra-K562 can efficiently expand human peripheral blood-derived NK/T cells in vitro( P<0.05). The cells expanded by PD-15 and G15Ra-K562 are mainly natural killing cell, CD8 + T and CD4 + T cells. Conclusions:The PD-15 fusion protein can specifically target the PD-1 molecule and has a strong human peripheral blood-derived NK/T cell expansion ability when combined with G15Ra-K562 feeder cells. These results shed light on selective expansion of PD-1 + lymphocytes in vitro.

Objective:To clarify the clinical efficacy of Yiqi Huoxue recipe in the treatment of liver fibrosis of chronic viral hepatitis.Methods:An open, positive-drug, parallel-controlled study method was applied. A total of 207 cases of liver fibrosis with chronic hepatitis B and C diagnosed with liver biopsy and transient elastography were selected. According to the principle of syndrome differentiation in traditional Chinese medicine, self-made Yiqi Huoxue recipe ( n = 127) and Fuzheng Huayu capsule ( n = 80) were used for the treatment course of 24-48 weeks. Change score of TCM symptom, liver biochemistry, liver stiffness measurement (LSM), and noninvasive liver fibrosis index [aspartate transaminase to platelet ratio index (APRI), and fibrosis-4 score (FIB-4)] were compared between the two groups to evaluate the therapeutic effect of Yiqi Huoxue recipe on liver fibrosis. Results:Yiqi Huoxue recipe group and Fuzheng Huayu capsule group baseline LSM, APRI and FIB-4 was compared, and there was no statistically significant difference between them ( P > 0.05). Yiqi Huoxue recipe and Fuzheng Huayu capsule received patients had improved symptom scores to a certain extent. Hepatic facies, discomfort over liver area, and soreness and weakness of waist and knees ( P < 0.05) was significantly improved in Yiqi Huoxue recipe than Fuzheng Huayu capsule. Liver biochemical indicators (ALT, AST, GGT, ALP) had gradually relapsed with the extension of treatment duration and the normalization rate between the two groups after 24 to 48 weeks had reached 100% vs. 100%, 100% vs. 93.8%, 96.8% vs. 92.3% and 87.5% vs. 81.8%. After 12 weeks of treatment, APRI values ??of both groups had significantly reduced, and after 48 weeks of treatment, LSM values of both groups had significantly improved. Moreover, Yiqi Huoxue recipe FIB-4 score was significantly improved after 48 weeks of treatment, and the difference was statistically significant compared to Fuzheng Huayu capsule group ( P < 0.05). After treatment, LSM, APRI, and FIB-4 total effectiveness in the two groups were 80.0% vs. 63.6%, P = 0.046; 68.4% vs. 52.0%, P = 0.052; 68.4% vs. 62.0%, P = 0.437, respectively. LSM total effectiveness was significantly higher in Yiqi Huoxue recipe treated group than Fuzheng Huayu capsule group. Conclusion:Traditional Chinese medicine Yiqi Huoxue decoction can be used as an optimal treatment for liver fibrosis of chronic viral hepatitis.

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.

Objective: To explore the clinical value of plasma heme oxygenase 1(HO-1) in the development of non-alcoholic fatty liver disease(NAFLD). Methods: Patients with NAFLD were selected from the Physical examination center and the Department of Traditional and Western Medical Hepatology of Third Hospital of Hebei Medical University. A combination of ultrasound and liver elastography was used to screen NAFLD patients and healthy persons. General clinical characteristics, peripheral blood cell count and liver biochemical test results were collected synchronously, plasma samples were retained, and plasma HO-1 level was detected by enzyme-linked immunosorbent assay. SPSS21.0 statistical software was used for statistical analysis, multivariate logistic regression analyses was used to analyse the independent risk factors affecting the incidence and progression of NAFLD. The diagnostic efficacy of indicators related to development of NAFLD was assessed by the receiver operating characteristic curve(ROC). Results: A total of 328 patients with NAFLD and 113 healthy controls were included. According to the liver biochemical results, the NAFLD group was divided into 148 patients with normal liver enzymes and 180 patients with abnormal liver enzymes. The level of HO-1 in the three groups was 9.09 ± 2.19, 14.38 ± 2.63, 17.00 ± 3.30 ng/ml, and was increased respectively of healthy controls, patients with normal liver enzymes and patients with abnormal liver enzymes. Analyzing plasma HO-1 levels of components associated with metabolic disorders suggests that components without metabolic syndrome(9.83 ± 3.21) < components with 1 metabolic syndrome(13.59 ± 3.72) < components with 2 or more metabolic syndrome(16.09 ± 3.41), P < 0.001. The results of HO-1 level stratification analysis showed that WBC, ALT, AST, GGT, TG increased as HO-1 level increased, and the pairwise difference was statistically significant (P < 0.001). The WBC count of NAFLD is significantly higher than healthy group(6.79 ± 1.62 vs 5.68 ± 1.36, P < 0.001). The univariate and multivariate regression analyses of all the subjects showed that HO-1, TG and BMI were prognostic factors for the occurrence of NAFLD and HO-1, TC, GLU were prognostic factors for the progression of NAFLD, P < 0.05. The ROC analysis showed that HO-1 was reliable markers for predicting the occurrence and progression of NALFD, the sensitivity and specificity were respectively 85.10%, 92.90% and 38.33%, 95.27%. Conclusion Plasma HO-1 can predict the occurrence and progression of NAFLD and is expected to be a novel molecular diagnostic marker for NAFLD and NASH.

Direct-acting antiviral agents (DAAs) are the main antiviral therapeutics for hepatitis C virus-related decompensated stage cirrhosis. DAAs of NS3/4A protease inhibitors use is not recommended for patients with decompensated cirrhosis due to characteristics of DAAs metabolism in liver. The recent guidelines have recommended sofosbuvir (SOF)-based plan including pan-genotype plan of sofosbuvir(SOF)/velpatasvir (VEL), sofosbuvir combined with daclatasvir (DCV), genotype 1,4,5,6 specific plan of sofosbuvir (SOF) / ledipasvir (LDV) for 24 weeks or above in combination with ribavirin for 12 weeks because NS5B and NS5A inhibitors has no obvious effect on CYP450 enzyme system and achievement of sustained virological response (SVR) rates at 12/24 weeks is achievable in 88% ~ 100%, and liver reserve function improves in 42% ~ 53% of patients. Furthermore, approximately 15.5% ~ 49% of patients waiting for liver transplantation after treatment with DAAs do not require liver transplantation for short-term and 10.3% ~19.2% of patients receiving SOF/LDV, and SOF combined with DCV not needed liver transplantation. Thus, the clinical application of DAAs provides a safe and reliable antiviral treatment plan for hepatitis C virus-related decompensated stage cirrhosis.

Objective To explore the clinical value of plasma heme oxygenase l(HO-l)in the development of non-alcoholic fatty liver disease(NAFLD).Methods Patients with NAFLD were selected from the Physical examination center and the Department of Traditional and Western Medical Hepatology of Third Hospital of Hebei Medical University.A combination of ultrasound and liver elastography was used to screen NAFLD patients and healthy persons.General clinical characteristics,peripheral blood cell count and liver biochemical test results were collected synchronously,plasma samples were retained,and plasma HO-1 level was detected by enzyme-linked immunosorbent assay.SPSS21.0 statistical software was used for statistical analysis,multivariate logistic regression analyses was used to analyse the independent risk factors affecting the incidence and progression of NAFLD.The diagnostic efficacy of indicators related to development of NAFLD was assessed by the receiver operating characteristic curve(ROC).Results A total of 328 patients with NAFLD and 113 healthy controls were included.According to the liver biochemical results,the NAFLD group was divided into 148 patients with normal liver enzymes and 180 patients with abnormal liver enzymes.The level of HO-1 in the three groups was 9.09±2,19,14.38±2.63,17.00±3.30 ng/ml,and was increased respectively of healthy controls,patients with normal liver enzymes and patients with abnormal liver enzymes.Analyzing plasma HO-1 levels of components associated with metabolic disorders suggests that components without metabolic syndrome(9.83±3.21)