Fibroblast growth factor receptor (FGFR) 2 gene fusion plays an important role in the pathogenesis of cholangiocarcinoma (CCA) . The method of targeting FGFR2 has been listed as the major therapy for advanced CCA. Adenosine triphosphate (ATP) -competitive FGFR inhibitors, represented by infigratinib and pemigatinib, effectively delay tumor progression and prolong patients survival, and are the first-line drugs for advanced CCA patients with FGFR2 fusion. However, almost all the patients treated with infigratinib eventually develop resistance, which require the combination with other drugs. Futibatinib may serve as a later-line drug for advanced CCA patients with V564F mutation after infigratinib resistance. For the infigratinib-resistant CCA patients harboring aberrant activation of the mitogen-activated protein kinase (MAPK) pathway, combination of the MAPK inhibitor or the heat shock protein 90 inhibitor may be considered as a novel therapeutic option.

Triple-negative breast cancer (TNBC) represents a distinct subtype of breast cancer, characterized by unique clinical traits including early lung metastasis, elevated recurrence rates, and diminished survival prospects. Owing to the lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, concrete therapeutic targets remain elusive, thereby confining available clinical treatment methods. In the context of advanced TNBC, chemotherapy remains the predominant therapeutic approach. In recent years, with the in-depth study of tumor microenvironment, new immunotherapy targets have been discovered one after another. Thus, immunotherapy-based combined therapy strategies have brought new hope in patients with advanced TNBC.

Epidermal growth factor receptor (EGFR) -mutant advanced non-small cell lung cancer (NSCLC) was previously regarded as a cold tumor according to tumor immune microenvironment (TIME) . However, recent studies have found that EGFR-tyrosine kinase inhibitors (EGFR-TKIs) treatment can transform the host immunity from immunosuppressive to immunosupportive state, bringing new hope for immunotherapy. There are four main therapeutic strategies for patients after EGFR-TKIs acquired resistance: immunotherapy alone (Im) , immunotherapy plus chemotherapy (Im+C) , immunotherapy plus antiangiogenic drugs (Im+A) , and immunotherapy combined with antiangiogenic drugs and chemotherapy (Im+A+C) . Among them, the efficacy of Im is extremely limited, being significantly lower than that of chemotherapy alone, while there is still scarce evidence for the efficacy of Im+A with few clinical studies. The combination of Im+C and Im+A+C shows better efficacy than chemotherapy alone. Im+A+C has a superior clinical outcome to Im+C. Additionally, the EGFR L858R mutation subgroup benefits more from Im+C than the EGFR 19 del mutation subgroup. The T790M-negative subgroup has a greater benefit from Im+A+C than the T790M-positive subgroup. In general, the strategy of combining immunotherapy with chemotherapy and/or an antiangiogenic drug represents a novel and promising method for treating EGFR-mutant NSCLC after EGFR-TKI failure.

Immunotherapy represented by PD-1/PD-L1 inhibitors has become the main treatment of malignant tumors. However, the adverse events caused by immunotherapy can not be ignored. Among them, dermatological immune-related adverse events (irAEs) occur with the highest incidence. Most dermatological irAEs belong to grade Ⅰ-Ⅱ, which does not affect the application of PD-1/PD-L1 inhibitors. The pathogenesis of dermatological irAEs is not fully understood. The most common types of dermatological irAEs are rash, pruritus and vitiligo. The domestic PD-1 inhibitor camrelizumab has unique adverse reactions of reactive cutaneous capillary endothelia proliferation (RCCEP) . It is found that dermatological irAEs can predict the clinical efficacy of PD-1/PD-L1 inhibitors in patients with malignant melanoma and non-small cell lung cancer (NSCLC) , especially RCCEP can be used as a potential biomarker of the efficacy of camrelizumab in the treatment of NSCLC, hepatocarcinoma, and esophageal cancer.

Objective:To analyze the clinical features of tuberculous peritonitis (TBP).Methods:The clinical data of 252 TBP patients admitted to three hospitals in Wuhu area from January 2014 to June 2020 were retrospectively analyzed, and the clinical characteristics of TBP patients of different genders and ages were compared. SPSS 26.0 software was used to analyze the data.Results:Among 252 TBP patients, 130 were males (51.6%) and 122 were females (48.4%). History of abdominal surgery, abdominal masses, reproductive disorders, genital tuberculosis, and delay in diagnosis were more common in female patients (all P<0.01); while fever, cough/sputum expectoration, intestinal tuberculosis and active tuberculosis were more common in male patients (all P<0.01). The proportion of adenosine deaminase in ascites (ADA) ≥35 U/L, strong positive tuberculin test or T-cell spot test in middle-aged and elderly patients was lower than that in young patients ( P<0.01), but there was no significant difference between different genders. Compared with young patients, middle-aged and elderly patients had a low complete response rate, a high proportion of irregular medications, a high incidence of gastrointestinal reactions, liver damage and overall adverse reactions (all P<0.05). Conclusion:Female patients with TBP have fewer symptoms of systemic tuberculosis and high rate of delay in diagnosis, and are prone to complicated with reproductive tuberculosis. In middle-aged and elderly patients with TBP, the sensitivity of ADA and tuberculosis tests is decreased, and the anti-tuberculosis therapy is less effective. The study indicates that the clinical diagnosis and treatment of TBP should be optimized based on the gender and age of patients.

Objective To explore the effect of atorvastatin on the proliferation and apoptosis of K562 cells andto investigate its mechanisms.Methods The cells were treated by different concentrations of atorvastatin.The CCK-8 assay was employed to detect the cell proliferation.The cell apoptosis was detected by AnnexinV-FITC/PI dual staining;the flow cytometry was used to detect the cellular cycle;the activities of caspase-3,-8,-9 were detected by the colorimetric method;qRT-PCR was employed to measure the mRNA expression levels of Bcl-2 and PDCD5 in K562 cells.Results Atorvastatin could inhibit the proliferation of K562 cells in a time-and dose-dependent manner(P＜0.05);and induced the apoptosis of K562 cells,the percentage of G0/G1 phase cells was increased after atorvastatin treating k562 cells(P＜0.01),while the percentage of S phase cells was decreased(P＜0.01),moreover which showing the concentration dependence(P＜0.01);atorvastatin activated the caspase-3,-8,-9 (P＜0.01);down-regulated Bcl-2 mRNA expression and up-regulated PDCD5 mRNA expressionin a concentration dependence(P＜0.01).Conclusion Atorvastatin can inhibit the proliferation and induce apoptosis in K562 cells.

Objective To observe the effect of anti NRP-1 b1/b2 monoclonal antibody (NRP-1mAb) on migration and invasion of gastric cancer cell line BGC-823, and to explore the possible mechanism. Methods NRP-1mAb was prepared in the laboratory, and the purity of antibody was detected by flow cytometry. The different concentrations of NRP-1mAb were added into the culture medium of gastric cancer cell line BGC-823. The migration and invasion of cells after 12 hours was observed by using Transwell method. The phosphorylation of related signal proteins after NRP-1mAb was detected by Western blot analysis. Results When NRP-1mAb prepared by patented technology had the effects on BGC-823 cells after 12 hours, the number of migration and invasion of BGC-823 cells was reduced. The number of cells through the basement membrane in the control group (blank) and the administration group (NRP-1mAb 25, 100, 400 μg / ml) were 167 ± 9, 138 ± 5, 98 ± 5, 36 ± 4, respectively (F = 22.6, P< 0.01); the number of cells through the filtration membrane were 231 ± 40,224 ± 19,176 ± 26,124 ± 34,respectively(F=26.63,P<0.01). There were statistically significant differences between the administered group and the control group at 100 and 400 μg/ml (all P< 0.001). High concentration of NRP-1mAb (100 μg/ml) decreased the phosphorylation level of Akt after 10 minutes' function on gastric cancer cells. However, it was difficult to detect phosphorylated Akt after 30 minutes. Conclusion NRP-1mAb may inhibit the migration and invasion of gastric cancer cell line BGC-823 by decreasing the phosphorylation of Akt, which is positively correlated with the concentration.

Objective To evaluate GGT in combination with B ultrasound for the diagnosis of biliary atresia (BA) infants suffering from obstructive jaundice.Methods A retrospective analysis was made on 69 sick infants including 55 BAs and 14 non-BAs as identified by intraoperative cholangiography.The preoperative laboratory GGT and ultrasound data were collected and analyzed.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy were compared.Results BA patients had significantly higher GGT than Non-BA patients (t =-4.164,P ＜ 0.05).The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of GGT ＞ 306 U/L were 69.1％,92.9％,97.4％,43.3％,73.9％,respectively.In BA group,abnormal gallbladder was significantly associated with proadening portal vein,broadening hepatic artery compared with Non-BA patients (x2 =9.995,P ＜0.05).The accuracy of abnormal gallbladder on ultrasound was 78.3％.When two method combined for the diagnosis of BA,the sensitivity,specificity,positive predictive value,negative predictive value were 92.7％,92.9％,98.1％ and 76.5％ and accuracy can reach 92.8％.Conclusions For obstructive jaundice infants with GGT ＞ 306 U/L and abdominal gallbladder ultrasound finding intraoperative cholangiography should be carried out to make definite diagnosis of BA.

Background and purpose: Gene chip is a nucleic acid sequence analysis method which is based on hybridization. It is a high-through put assay which can widely detect the level of gene expression in different tissues and cell types. This study aimed to compare and bioinformatically analyze differentially expressed genes between higher malignant degree of prostate cancer tissues and prostate inflammation tissues. Methods: The total RNAs were isolated from tissues of prostate cancer and prostate inflammation by TRIzol method and then purified, reversely tran-scribed to cDNA with incorporating biotin labeling probe, hybridized with Affymetrix Human U133 Plus 2.0 (covering 47000 transcripts,representing 38500 distinct genes). Picture signals of fluorescence in gene array were scanned and differential expression of gene in two tissues were compared by Command Console Software 4.0. These differential expressed genes were analyzed by bioinformatics methods finally. Results: According to the fold change ≥2, P<0.05, 1819 differential expression genes including 1025 up-regulated genes and 794 down-regulated genes were discovered. GO enrichment analysis displayed that these differentially expressed genes were mainly involved in cell cycle, cell metabolism, etc. KEGG pathway analysis found that these genes were mainly involved in some metabolism pathways including purine nucleotide metabolism. The interactions between the proteins encoded by these genes were analyzed by STING. Twenty key nodes genes including TPX2, ANLN, NUSAP1, MELK, DLGAP5, KIF11, TOP2A, RRM2 were dis-covered. Then this study revealed CEP55 and ANLN might be related to the occurrence and metastasis of prostate cancer by looking through literature. Conclusion: During the development of prostate cancer, the activation of genes related to cell cycle and cell migration, the abnormalities of genes related to metabolism and the inhibition of genes related to cell adhesion play critical roles in the development of prostate cancer. CEP55 and ANLN were related to the occurrence and prognosis of prostate cancer by systematic analysis which provided a valuable clue for the next experiment.

Background and purpose:Hypermethylated in cancer 1 (HIC1) is silenced in multiple cancer cells and tissues by DNA methylation of epigenetic modification, which may modulate the initiation and progression of tumors. However, there are few reports about this phenomenon in prostate cancer. This study aimed to investigate the status of HIC1 promoter methylation in prostate cancer using methylation methods.Methods:Methylation-specific polymerase chain reaction (MSP) and bisulfate sequencing PCR (BSP) were used to detect the methylation status ofHIC1 promoter in prostate cancer cell lines PC3 and C4-2B, prostate normal cell line PrEC, primary Chinese PCa tissues and the respective healthy control cases.HIC1 expression level was respectively determined by reverse transcription-PCR (RT-PCR) and Western blot assays in PC3, C4-2B and PrEC cells treated with 5-Aza-CdR.Results:We found that the percentages of HIC1 promoter methylation were 78.23%, 72.15% and 10.63% in PC3, C4-2B and PrEC cells by MSP analyses. Moreover, the levels of methylatedHIC1 promoter in 36 primary Chinese PCa tissues compared with the respective healthy control cases were 80.30%vs 31.56%. Expressions ofHIC1 mRNA and protein level were restored in PC3 and C4-2B cells after 5-Aza-CdR treatment.Conclusion:These findings demonstrate thatHIC1 promoter region is hypermethylated in prostate cancer, which results in silence or downregulation ofHIC1. The status ofHIC1 methylation can be a valuable marker in the early stage of prostate cancer and a potential therapeutic target.