PI3K/AKT/mTOR signaling pathway plays a crucial role in cell proliferation, survival, differentiation, motility and intracellular transport. PI3Kδ, an isoform of PI3K, is highly expressed in B lymphocytes and is involved in the malignant progression of B-cell lymphoma. Thus, PI3Kδ has emerged as an attractive target for the development of anti-B-cell lymphoma drugs. Currently, there are several PI3Kδ inhibitors approved by the FDA for the treatment of B-cell lymphoma, each with its own characteristics, but also with varying degrees of adverse effects in clinical practice. Due to the complexity and diversity of the pathogenesis of B-cell lymphoma, single-target PI3Kδ inhibitors often have limited efficacy and are prone to drug resistance, and need to be combined with chemotherapy or other targeted drugs to enhance their efficacy. The future trend is to design novel inhibitors with higher efficacy and lower toxicity or to develop novel combination regimens with other chemotherapy, radiotherapy, and target drugs to acquire better anti-tumor effects with reduced adverse effects. This review summarizes the PI3Kδ inhibitors that have been approved for the treatment of B-cell lymphoma or are still in clinical trials, mainly focusing on their characteristics, adverse effects and combination regimens.

Objective To investigate the risk factors for pediatric acute perforation appendicitis,and to construct a nomogram predictive model and conduct the verification.Methods A total of 426 children patients with appendectomy in this hospital from June 30,2020 to June 30,2022 were selected as the study subjects 340 children with acute appendicitis admitted to the hospital from 30 June 2020 to 28 February 2022 were the training set and 86 children patients with appendicitis hospitalized in this hospital from March 1,2022 to June 30,2022 conducted the external validation(verification set).The univariate and multivariate logistic regression models were employed to analyze the independent risk factors of pediatric acute perforation appendicitis.The nomograms predictive model was constructed.The receiver operating characteristic(ROC)curve and calibra-tion curve were used to evaluate the predictive efficiency of the model.The decision curve analysis(DCA)was used to evaluate the application value of the model.Results Of the 426 children,198 were perforated and 228 were not perforated.The univariate and multivariate logistic regression analyses revealed that elevated C-reac-tive protein(CRP),presence of stercorolith in appendiceal cavity,time of onset to visiting hospital ≥2 d and body temperature ≥37.3 ℃ were the independent risk factors for pediatric acute perforation appendicitis(P＜0.05).The Hosmer-Lemeshow test demonstrated that the nomogram predictive model had good fitting(P=0.869),and the area under the curve(AUC)for the training and validation sets were 0.808 and 0.860 respectively,showing the good predictive ability of the model.The calibration curve closely approach the ideal diagonal.The model showed good discrimination,consistency and accuracy.The DC A revealed that the curve was far away from oblique and horizontal lines,and the model had good clinical practicability.Conclusion The constructed nomogram model of pediatric acute perforation appendicitis has good predictive ability and may help clinic to identify as early as possible.

Objective To investigate the expression of multi-glycan in serum of patients with dual-phenotype hepatocellular (DPHCC) and its clinical significance. Methods Serum samples were collected from 65 patients with DPHCC, 80 patients with primary hepatocellular carcinoma (HCC), and 120 patients with liver cirrhosis (LC) who were treated in Mengchao Hepatobiliary Hospital of Fujian Medical University from June 2019 to December 2020. DNA sequencer-aided fluorophore-assisted carbohydrate electrophoresis was used to measure the expression of N-glycan in serum, The measurement data of normal distribution were compared by t -test between the two groups and analysis of variance between multiple groups; The measurement data with non normal distribution were compared by Mann-Whitney U test between the two groups and Kruskal-Wallis H test between multiple groups, the chi-square test was used for comparison of categorical data between groups.The logistic regression method was used to establish the common index model. The efficacy of AFP, PIVKA - Ⅱ, CEA, CA19-9 and multi glycan in the diagnosis of DPHCC was evaluated by receiver operating characteristic (ROC) curve, and the area under ROC curve (AUC) was compared by Z test. Results There was a significant difference in multi-glycan between the DPHCC group and the HCC group ( P < 0.001), while there were no significant differences in AFP, PIVKA-Ⅱ, CEA, CA19-9, and SUM between the two groups ( P =0.924, 0.084, 0.442, 0.924, and 0.206). Multi-glycan had an area under the ROC curve (AUC) of 0.775, which was significantly higher than that of AFP (0.507), PIVKA-Ⅱ (0.584), CEA (0.537), CA19-9 (0.505), and SUM (0.561), and multi-glycan had a sensitivity of 69.23%, which was increased compared with the other 5 items. There were significant differences in multi-glycan, AFP, PIVKA-Ⅱ, CA19-9, and SUM between the DPHCC group and the LC group (all P < 0.001), but there was no significant difference in CEA between the two groups ( P =0.14). Multi-glycan had an AUC of 0.780, which was also higher than that of AFP (0.767), PIVKA-Ⅱ (0.743), CEA (0.566), CA19-9 (0.689), and SUM (0.713), and multi-glycan had a sensitivity of 89.23%, which was increased compared with the other five items. Conclusion Multi-glycan can be used as one of the indicators for the auxiliary diagnosis of DPHCC.

Objective:To establish a lectin enzyme-linked immunosorbent assay (lectin-ELISA) for the dection of sialylated fetuin-A and to explore the clinical diagnostic value of sialylated fetuin-A in hepatocellular carcinoma (HCC).Methods:From January 2017 to December 2020, 300 HCC patients and 160 disease controls, including 36 liver cirrhosis subgroups and 124 chronic hepatitis B subgroups, were collected from Shanghai Eastern Hepatobiliary Surgery Hospital. At the same time, 100 healthy subjects were collected as healthy controls. Lectin-ELISA method for detecting sialylated fetuin A was established based on the principle that Sambucus nigra lectin (SNA) can recognize the structure of α-2, 6-linked sialic acid residues. Differences between groups were compared using t-test or analysis of variance. Logistic regression method was used to establish the multi-index joint detection model, and receiver operating characteristic curve (ROC) was used to evaluate the efficacy of single index and joint detection model in the diagnosis of HCC.Results:A lectin-ELISA method for the detection of serum Sia-fetuin A was established. The linear regression coefficient of the system was 0.978 5, and the precision evaluation and interference experiments were in line with the clinical detection requirements. Using this method to detect serum Sia-fetuin A levels in each group, the levels of HCC group, disease control group and healthy control group were 1.362±0.310, 1.199±0.370, 1.086±0.420, respectively, and the three groups decreased in turn. The areas under the curve of Sia-fetuin A, α-fetoprotein, and their combined detection models for differential diagnosis of HCC were 0.790, 0.809, and 0.860, respectively. The diagnostic model had a sensitivity of 79.3% (238/300) and a specificity of 95.0% (247/260). Among the 300 patients in the HCC group, 138 (46%) patients were negative for serum AFP (<20 μg/L), and their serum Sia-fetuin A level was 1.364±0.305. Combining the disease control group and the healthy control group into the non-Cancer group, the serum Sia-fetuin A level was 1.146±0.381. The serum level of Sia-fetuin A in AFP-negative HCC patients was higher than that in non-HCC group ( t=6.134, P<0.001). The areas under the curve of Sia-fetuin A and the combined diagnostic model for the diagnosis of AFP-negative HCC were 0.776 and 0.919, respectively. The combined diagnostic model had a sensitivity of 93.4% (129/138) and a specificity of 77.3% (201/260). Conclusion:Serum Sia-fetuin A and combined determination model can provide a new auxiliary diagnostic index for AFP-negative HCC.

Circulation biomarker detection is one of the most feasible options for disease screening and monitoring. Focusing on the biomarkers of end stage liver diseases (liver cirrhosis and hepatocellular carcinoma), this article summarized the classification of biomarkers, the exploration and translation of new biomarkers, as well as the applications of the algorithms of the biomarkers. The key points involved in both new biomarker exploration and algorithm construction were addressed. The comprehensive application of available markers, using algorithms, is strongly recommended and should be strengthened in the future for precise clinical management and high-risk predictions in diseases such as hepatocellular carcinoma.

Several immune checkpoint inhibitors (ICIs) have been approved for use in patients with advanced non-small cell lung cancer (NSCLC) based on the results of randomized controlled trials (RCTs), bringing new hope to patients with such disease. However, the applicability of the RCT results is limited due to their strict inclusion criteria and specific clinical settings. Real-world studies (RWS) can integrate data from real-life practice with long-term clinical observations and follow-up, therefore building up the real-world evidence to complement that provided by conventional clinical trials. ICIs have been used in clinical practice in multiple countries and areas for several years. Here, we aim to provide an overview of the efficacy and safety of ICIs in patients with NSCLC included in the large expanded access program and multicenter retrospective observational studies and review the impact of different populations to provide a reference for ICIs use in China.

Objective    To evaluate the influence of clinical, pathological and treatment factors on the prognosis of thymic carcinoma patient accepted surgical treatment. Methods    Retrospective analysis was performed on 38 patients with thymic carcinoma undergoing surgical treatment between January 2008 and December 2017. The association between the prognostic factors including age, sex, thymectomy, radical resection, pathological type, TNM stage, Masaoka-Koga stage, tumor size, and survival was assessed using the Kaplan-Meier method. Results    The 5-year overall survival rate of our cohort was 51.9%. Kaplan-Meier univariate survival analysis showed that radical resection (P=0.003), TNM stage (P=0.038), Masaoka-Koga stage (P=0.033), and tumor size (P=0.030) were related to the prognosis of patients with thymic carcinoma. Radical resection was also validated as an independent prognostic factor in multivariate Cox analysis (P=0.009, hazard ratio 2.31, 95%CI 1.23-4.33). Conclusion    Radical surgical treatment could improve the prognosis of patients with resectable thymic carcinoma.

Objective To investigate the expression of melanoma antigen- encoding gene (MAGE) A1 protein in esophageal squamous cell carcinoma, and explore its correlation with the clinicopathological factors and prognosis. Methods A retrospective analysis was performed on 197 patients with esophageal squamous cell carcinoma who accepted radical surgical treatment from January 2006 to December 2012. The expressions of MAGEA1 protein in these specimens of cancer tissue and cancer adjacent tissue were detected by immunohistochemistry with tissue microarray technology. Results MAGEA1 protein was expressed in cytoplasm and nucleus of tumor cells. The positive expression rate of MAGEA1 protein in cancer tissue was significantly higher than that in cancer adjacent tissue: 73.6％ (145/197) vs. 5.6％ (11/197), and there was statistical difference (P<0.01). The positive expression of MAGEA1 protein had no correlations with sex, age, history of smoking/drinking, family history of upper gastrointestinal cancer, depth of tumor invasion, lymph node metastasis, tumor differentiation, location and TNM stage (P>0.05). Kaplan-Meier survival analysis result showed that the 5-year survival rate in patients with MAGEA1 protein positive expression was significantly lower than that in patients with MAGEA1 protein negative expression (37.2％ vs. 53.8％), and there was statistical difference (P=0.018). Multivariate analysis result showed that MAGEA1 protein positive expression was an independent predictor of prognosis in esophageal squamous cell carcinoma patients (HR=1.91, 95％CI 1.22 to 2.98, P = 0.004). Conclusions The expression of MAGEA1 protein is abundant in esophageal squamous cell carcinoma, and is related to worse clinical outcome. MAGEA1 protein could be a candidate target for tumor immunotherapy.

Objective: To explore the value of GALAD model, including gender, age, AFP, AFP-L3 and DCP in diagnosis of primary hepatocellular carcinoma and prediction of microvascular invasion (MVI). Methods: Using retrospective study method, 5 919 patients with primary hepatocellular carcinoma (HCC) who received radical operation from January 2015 to December 2018 in Eastern Hepatobiliary Surgery Hospital were enrolled into study group. At the same time, 1 745 patients with benign liver diseases (BLDs) were enrolled into control group. The concentration of DCP was detected by Lumipulse G1200 automatic immune analyzer, and the concentration of AFP was detected by Cobas e601 automatic immune analyzer. AFP-L3 was detected by affinity adsorption centrifugation. The non-parametric Mann Whitney test was used to compare the difference between two groups. The chi square test was used to compare the rates. The diagnostic value of single serological marker and GALAD model for primary hepatocellular carcinoma was analyzed. The predictive effect of GALAD model on MVI of primary hepatocellular carcinoma was evaluated. Results: Compared with single serum marker, the diagnostic value of GALAD model is higher. When the cutoff value is -0.33, the diagnostic sensitivity, specificity and accuracy reach to 91.9% (5 440/5 919), 86.8% (1 515/1 745) and 90.7% (6 955/7 664), respectively. The area under the curve can reach 0.960 [95%CI (0.955-0.964)]. Compared with no MVI (M_O) group, the value of GALAD model in MVI low-risk group (M₁), MVI high-risk group (M₂) and MVI (M₁₊₂) were significantly higher (Z values were-12.517, -22.883, -21.655, P<0.05), Galad model predicts MVI (M2) in high risk group,AUC was 0.717 [95%CI (0.701-0.733)] (M₀ ratio M₂). Conclusion GALAD model has better diagnostic performance in primary hepatocellular carcinoma and has certain predictive value for microvascular invasion.

Objective To discuss the efficacy of laparoscopic ureteroureterostomy for upper pole hydronephro-sis and ureteral dilatation in children with complete duplex kidney.Methods The clinical data of 14 patients (15 units in total)who underwent laparoscopic ureteroureterostomy from April 2016 to October 2017 were retrospectively analyzed. Nine out of 14 cases had repeated urinary tract infections(UTI)and other symptoms[6 cases in group A:patients without vesicoureteral reflux(VUR)but presenting urinary tract infection (UTI)symptoms,3 cases in group C:patients diagnosed with VUR];5 cases of asymptomatic patients were selected as group B.All the 14 cases had upper pole hydronephrosis and ureteral dilatation.Preoperative examinations included ultrosonograpy,urinary magnetic resonance urography(MRU), intravenous pyelography (IVP),voiding cystourethrogram(VCUG),and nuclear renal scanning.It was found that 4 cases had ureterocele;3 cases had recurrent cystoureteral reflux (group C)before operation,and 1 case had cystoureteral re-fluxed after replantation.Results Laparoscopic surgery was successful in all of 14 children.None of them were shifted to open surgery because of abdominal viscera injury bleeding.The operation duration was 85－140 min.The average posto-perative hospital stay was 5.58 days.There was neither urinary anastomotic leakage nor UTI.Fourteen cases were followed up and the postoperative follow－up period was 7－23 months.No cases developed urinary tract infection except 2 cases with vescioureteral reflux.Ultrasound examination showed that the upper renal parenchyma of 5 children was thicker,ul-trasonography showed that upper pole hydronephrosis was better and ureteroceles were smaller.There was no complication such as lower pole hydronephrosis.The symptoms of urinary tract infection disappeared after operation.Conclusions Laparoscopic ureteroureterostomy can treat renal duplication with less trauma,and it is safe and effective.It can be one of therapeutic regimen to treat low－functional upper pole hydronephrosis and ureteral dilatation in renal duplication.Howe-ver,this procedure cannot be used for vescoureteral reflux cases because of high rate of stump infection.