Abstract Inhibitor of DNA binding 1(ID1) is a crucial regulator of cell differentiation and plays a significant role in maintaining normal hematopoietic differentiation and development. Due to the lack of DNA-binding motif, ID1 functions as a dominant-negative inhibitor of basic helix-loop-helix factors to antagonize their abilities to bind to DNA and transcriptionally regulate target genes. Abnormal expression of ID1 is strongly associated with various hematologic disorders, including myeloid and lymphoblastic leukemia, multiple myeloma and myeloproliferative neoplasms. ID1 acts as a potential oncogene by participating in multiple signaling pathways that promote the malignant proliferation, invasion and therapy resistance in leukemic cells. Significant strides have yielded promising antileukemic effects of ID1 inhibitors, both alone and in combination with targeted therapies against oncogenic signaling pathways. Here, we review the relationship between ID1 expression and the initiation and progression of blood disorders, and summarize the clinical significance of ID1 as a novel therapeutic target and potential prognostic biomarker for hematologic malignancies.

Objective To retrospectively analyze multicenter data from domestic sources, aiming to explore the link between intrahepatic cholangiocarcinoma (ICC) tumor size and prognosis, establishing a classification system based on tumor size. Methods Between December 2011 and September 2018, 280 ICC patients from 13 hospitals were included. The tumor size prognosis cutoff was identified by the minimum P-value method, and the classification's overall survival related effectiveness was assessed by Kaplan-Meier analysis. Results All 280 patients were divided into the group of tumor maximum diameter ≤4 cm and >4 cm. Tumor size was confirmed as an independent prognosis factor by multivariate COX regression analysis (HR=2.110, 95% CI: 1.358-3.280). Conclusions The tumor size dichotomy classification system based on the Chinese patient group can expediently predict ICC prognosis and offers an important basis for selecting post-operative individualized adjuvant therapy and follow up plans.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Case 1,a 69-year-old male patient,was admitted to our hospital due to"dizziness,fatigue,nausea,diarrhea,and oral bleeding for 10 d",with a recent history of field farming work.The patient exhibited leukopenia,thrombocytopenia,and clinical manifestations of multi-organ dysfunction,including coagulation dysfunction,liver function abnormalities,gastrointestinal disorders,myocardial injury,and respiratory failure.Bone marrow aspiration smear revealed hemophagocytosis,and out-of-hospital testing for the severe fever with thrombocytopenia syndrome bunyavirus was positive.The patient was diagnosed with severe fever with thrombocytopenia syndrome(SFTS)complicated by hemophagocytic lymphohistiocytosis(HLH).After diagnosis,glucocorticoid combined with ribavirin treatment was initiated.However,the patient still died,which may be related to factors such as delayed medical consultation,advanced age,and poor control of viral replication.Case 2,a 73-year-old male patient,was admitted to our hospital due to"fatigue for 1 week",with a recent history of field farming work.The patient also presented with leukopenia and thrombocytopenia,combined with liver and coagulation function abnormalities.Bone marrow aspiration smear showed hemophagocytosis,and the patient was highly suspected of SFTS with HLH.We empirically initiated preemptive treatment with favipiravir for antiviral therapy,combined with glucocorticoid for anti-inflammation,to early inhibit novel bunyavirus replication and cytokine storm.Subsequent testing reported the severe fever with thrombocytopenia syndrome bunyavirus nucleic acid quantification as 2.69×103 50%tissue culture infective dose(TCID50)/mL,confirming the diagnosis of SFTS with HLH.The patient's clinical symptoms and various indicators generally improved.Review of these two similar cases suggests that early empirical preemptive use of favipiravir to control viral replication in clinical practice may improve the treatment and prognosis of patients with SFTS complicated by HLH.

Case 1,a 69-year-old male patient,was admitted to our hospital due to"dizziness,fatigue,nausea,diarrhea,and oral bleeding for 10 d",with a recent history of field farming work.The patient exhibited leukopenia,thrombocytopenia,and clinical manifestations of multi-organ dysfunction,including coagulation dysfunction,liver function abnormalities,gastrointestinal disorders,myocardial injury,and respiratory failure.Bone marrow aspiration smear revealed hemophagocytosis,and out-of-hospital testing for the severe fever with thrombocytopenia syndrome bunyavirus was positive.The patient was diagnosed with severe fever with thrombocytopenia syndrome(SFTS)complicated by hemophagocytic lymphohistiocytosis(HLH).After diagnosis,glucocorticoid combined with ribavirin treatment was initiated.However,the patient still died,which may be related to factors such as delayed medical consultation,advanced age,and poor control of viral replication.Case 2,a 73-year-old male patient,was admitted to our hospital due to"fatigue for 1 week",with a recent history of field farming work.The patient also presented with leukopenia and thrombocytopenia,combined with liver and coagulation function abnormalities.Bone marrow aspiration smear showed hemophagocytosis,and the patient was highly suspected of SFTS with HLH.We empirically initiated preemptive treatment with favipiravir for antiviral therapy,combined with glucocorticoid for anti-inflammation,to early inhibit novel bunyavirus replication and cytokine storm.Subsequent testing reported the severe fever with thrombocytopenia syndrome bunyavirus nucleic acid quantification as 2.69×103 50%tissue culture infective dose(TCID50)/mL,confirming the diagnosis of SFTS with HLH.The patient's clinical symptoms and various indicators generally improved.Review of these two similar cases suggests that early empirical preemptive use of favipiravir to control viral replication in clinical practice may improve the treatment and prognosis of patients with SFTS complicated by HLH.

Objective:To explore the expression patterns of inhibitor of differentiation(ID)family in patients with chronic myeloid leukemia(CML)and analyze their clinical implications.Methods:Quantitative PCR and quantitative methylation-specific PCR were conducted to de-tect the transcript levels of ID2/ID3/ID4 and the methylation levels of ID4 in the bone marrow mononuclear cells of non-hematological ma-lignancies(acting as controls)and patients with CML treated at The Affiliated People's Hospital of Jiangsu University from January 2010 to December 2017.The clinical implications of ID family alterations were further analyzed.Results:ID2 and ID3 expression was significantly up regulated(P<0.001 and P<0.05,respectively),whereas ID4 expression was markedly down regulated in patients with CML(P<0.01).The re-ceiver operating characteristic curve demonstrated that the ID2 transcript level is a potential biomarker for distinguishing CML from controls(AUC=0.895,P<0.001).The frequency of ID4 promoter methylation in patients with CML was drastically higher than that in the controls(P=0.001).Moreover,ID4 methylation was negatively correlated with ID4 expression in patients with CML(r=-0.424,P=0.002).Clinically,CML with high ID2 expression occurred more frequently in males(P=0.040).Patients with low ID4 expression or high ID4 methylation showed a markedly higher frequency of an accelerated phase/blast crisis(P=0.003 and P<0.001,respectively).In addition,patients with CML in an accelerated phase/blast crisis exhibited markedly lower ID4 expression and higher ID4 methylation levels than those in the chronic phase(both P<0.001).Furthermore,univariate and multiple Logistic regression analyses revealed that the ID4 methylation level was an inde-pendent risk factor for CML progression(P=0.007).Conclusions:The ID family was differentially expressed in patients with CML;specifically,ID2 and ID3 expression was significantly increased,whereas ID4 expression was markedly decreased and correlated with ID4 promoter hy-permethylation.Hence,ID4 expression and methylation are confirmed to be associated with CML progression,and ID4 methylation could be an independent risk factor for CML progression.

Objective To investigate the impact of LncRNA FOXP4-AS1 regulating the EZH2/LATS2 axis on the proliferation and migration of bladder urothelial carcinoma(BUC)cells.Methods The Cancer Genome Atlas(TCGA)database and real-time quantitative PCR were utilized to analyze the expression of FOXP4-AS1 and LATS2 mRNA in BUC tissues.Cell proliferation was observed using MTT experiments,and migration was checked using Transwell assays.Western blot assays were performed to determine the expression of LATS2 and H3K27me3 proteins.RNA immunoprecipitation(RIP)and chromatin immunoprecipitation(ChIP)assays were employed to verify the relationship between FOXP4-AS1,EZH2 and LATS2.Results Compared with normal bladder tissues,FOXP4-AS1 expression was increased in tumor tissues,while LATS2 mRNA expression was decreased(P<0.01).Moreover,FOXP4-AS1 expression was elevated in EJ,T24,BIU-87,and 5637 cell lines compared to SV-HUC-1(P<0.01).The inhibition of FOXP4-AS1 resulted in a significant decrease in the proliferation,migration,and expression of H3K27me3 protein in BUC cells,while concurrently upregulating the expression of LATS2 mRNA and protein.Conversely,the overexpression of FOXP4-AS1 yielded contrasting effects(P<0.05).RIP and ChIP assays revealed that FOXP4-AS1 could recruit EZH2 to the promoter region of LATS2,leading to an enrich-ment of H3K27me3 in this region.Interference with LATS2 or EZH2 expression partially reversed the effects of FOXP4-AS1 silencing or overexpression on the proliferation and migration of BUC cells,with concomitant effects on LATS2 expression.Conclusion FOXP4-AS1 demonstrates a notable increase in expression in BUC,leading to a suppression of LATS2 expression through the recruitment of EZH2 to the promoter region of LATS2.This regula-tory process ultimately influences the proliferation and migration of BUC cells.

Objective:To analyze the impact of lymph node dissection on textbook outcomes (TO) and the prognosis of intrahepatic cholangiocarcinoma (ICC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 376 ICC patients who underwent hepatectomy in 4 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from December 2011 to December 2017 were collected. There were 242 males and 134 females, aged 57(range, 48-63)years. According to the criteria of TO, patients were classified as two cate-gories, including patients achieving TO and not achieving TO. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were represented as absolute numbers, and comparison between groups was conducted using the chi-square test, Yates adjusted chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Univariate and multivariate analyses were conducted using the Logistic regression model. The Kaplan-Meier method was used to draw survival curve. Survival analysis was conducted using the Log-rank test. Results:(1) TO situations. Of the 376 ICC patients who underwent hepatectomy, 199 cases achieved TO, including 40 cases with lymph node dissection and 159 cases without lymph node dissection, 177 cases did not achieve TO, including 76 cases with lymph node dissection and 101 cases without lymph node dissection. (2) Influencing factors for TO after hepatectomy of ICC patients. Results of multivariate analysis showed that lymph node dissection, microvascular invasion, nerve invasion and the volume of intraoperative blood loss >800 mL were independent risk factors for achieving TO after hepatec-tomy of ICC patients ( odds ratio=2.22, 2.95, 3.58, 4.09,95% confidence interval as 1.34-3.69, 1.43-6.07, 1.40-9.17, 1.35-12.43, P<0.05). Of the 116 patients with lymph node dissection, 40 cases achieved TO, 103 cases achieved R 0 resection, 38 cases had postoperative complications, 67 cases had delayed hospital stay. The above indicators were 159, 255, 41, 65 of 260 patients without lymph node dissection. There were significant differences in the above indicators between patients with and without lymph node dissection ( χ2=22.90, 15.16, 13.95, 37.78, P<0.05). (3) Follow-up. All the 376 patients were followed up for 19(range, 1-74)months. Of 199 patients achieving TO, the 1-, 2-and 3-year survival rates of 40 patients with lymph node dissection were 54.0%, 36.6% and 26.1%, respectively, versus 67.7%, 42.7% and 34.4% of 159 patients without lymph node dissection, showing no significant difference between them ( χ2=1.89, P>0.05). Of 177 patients not achieving TO, the 1-, 2-and 3-year survival rates of 76 cases with lymph node dissection were 58.9%, 25.7% and 10.3%, respectively, versus 53.0%, 28.5% and 17.2% of 101 cases without lymph node dissection, showing no significant difference between them ( χ2=0.25, P>0.05). Conclusions:Lymph node dissec-tion, microvascular invasion, nerve invasion and the volume of intraoperative blood loss >800 mL are independent risk factors for achieving TO after hepatectomy of ICC patients. Lymph node dissec-tion may increase the postoperative complication rate, prolong the hospital stay and decrease the rate of achieving TO. However, it does not affect the prognosis of patients.

The aberrant activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 （NLRP3） inflammasome as an essential component of the innate system is implicated in the pathogenesis of several human inflammatory diseases. Studies have confirmed its association with digestive system diseases such as ulcerative colitis， Crohn's disease， and acute pancreatitis， suggesting that the NLRP3 inflammasome plays a role in the initiation and progression of these diseases. Based on the mechanism of NLRP3 inflammasome activation and the pathways that mediate the inflammatory response， this article introduced the relationship between the NLRP3 inflammasome and the pathogenesis of multiple digestive system diseases and the Chinese and western medical therapies. Traditional Chinese medicine （TCM） has demonstrated definite effects on the NLRP3 inflammasome-mediated digestive system diseases. Some single Chinese medicines or TCM prescriptions can treat digestive system diseases by activating or inhibiting NLRP3 inflammasome activation. NLRP3 inflammasome can receive a variety of endogenous and exogenous stimulatory signals， which can initiate， activate， and mediate inflammatory responses. The inflammasome formation and downstream inflammatory cytokines are involved in not only the inflammatory responses but also the development and progression of multiple digestive system diseases. Therefore， the NLRP3 inflammasome can serve as an ideal target for disease treatment. The future rediscovery and in-depth studies of multiple inflammasomes will shed new light on the treatment of multiple digestive system diseases.