T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective:To understand the knowledge, attitudes, and behaviors of residents in areas endemic for severe fever with thrombocytopenia syndrome (SFTS) and the factors influencing these aspects, to provide a scientific basis for the prevention and control of SFTS among residents in endemic areas.Methods:A multi-stage sampling method was used to select subjects for a questionnaire survey, and the collected data were analyzed and compared.Results:The awareness rate of SFTS-related knowledge among residents in the endemic areas of Qingdao was 14.38%, while the awareness rate of tick-related knowledge was 69.78%. The mean score for protective attitudes among residents in the endemic areas was 24.50±4.09, and the mean score for protective behaviors was 11.20±2.76. Among residents of different ages, occupations, and educational levels, comparisons of SFTS-related knowledge awareness rates ( χ2=293.553, P<0.001; χ2=495.216, P<0.001; χ2=677.272, P<0.001), tick-related knowledge awareness rates ( χ2=29.986, P<0.001; χ2=23.239, P=0.002; χ2=41.003, P<0.001), protective attitude scores ( H=52.094, P<0.001; H=33.446, P<0.001; H=81.715, P<0.001), and protective behavior scores ( H=52.344, P<0.001; H=28.465, P<0.001; H=67.061, P<0.001) showed statistically significant differences. Comparisons of these same factors among residents of different genders showed no statistically significant differences ( χ2=1.159, P=0.282; χ2=0.298, P=0.585; t=-0.808, P=0.419; t=-1.229, P=0.219). Comparisons of tick-related knowledge awareness rates among residents with different frequencies of outdoor work showed no statistically significant differences ( χ2=5.367, P=0.147); however, comparisons of SFTS-related knowledge awareness rates, protective attitude scores, and protective behavior scores among residents with different frequencies of outdoor work showed statistically significant differences ( χ2=117.010, P<0.001; F=4.127, P=0.006; H=56.280, P<0.001). Multivariate linear regression analysis revealed that older age, lower educational level, and less frequent outdoor work were associated with lower protective behavior scores ( t=-3.479, P<0.001; t=4.861, P<0.001; t=-7.753, P<0.001). Conclusions:Residents in the epidemic areas of SFTS have a low level of knowledge, attitude and practice. Factors influencing protective behaviors include age, occupation, educational level, and frequency of outdoor work. Farmers are a group that requires particular attention.

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.

Objective: To explore the effect of interferon regulatory factor 2 binding protein 2 ( IRF2BP2) on the proliferation of acute myeloid leukemia ( AML) cells and its molecular mechanism． Methods: The CRISPR-Cas9 gene editing technology was used to knock out IRF2BP2 in human AML cell lines Kasumi-1 and U937，and West- ern blot was performed to detect the knockout efficiency of IRF2BP2 protein．Cell morphology was observed using a microscope．Cell phenotypes were analyzed by CCK-8 assay，colony formation experiments，and flow cytometry． RNA-Seq was performed to identify differentially expressed genes between the IRF2BP2 knockout group and the control group in the U937 cell line．Gene Set Enrichment Analysis ( GSEA) was conducted to explore the down- stream molecular mechanisms．Western blot was used to detect the expression of downstream differentially expressed genes．The Cleavage Under Targets and Tagmentation ( CUT＆Tag) technique was applied to identify the direct tar- gets of the IRF2BP2 protein，and the corresponding binding signals were visualized using the Integrated Genomics Viewer ( IGV) ． Results: Compared with the control group，after knocking out IRF2BP2，the CCK-8 experiment showed that AML cell proliferation was inhibited ( P ＜0. 05) ; the number of colonies in the IRF2BP2 knockout group decreased ( P＜0. 05) ，and the proportion of G1 phase was prolonged ( P＜0. 05) ; in U937 cell lines，knoc- king out IRF2BP2 resulted in significant enrichment of differential genes in myelocytomatosis oncogene ( MYC) -re- lated signaling pathways，and the protein expression levels of pathway molecules MYC，cyclin-dependent kinase 4 ( CDK4) ，and cyclin － dependent kinase 2 ( CDK2 ) decreased with the downregulation of IRF2BP2; using IRF2BP2 antibodies in U937 cell lines for CUT＆Tag experiments，IGV visualization analysis showed a significant increase in signal peaks in the MYC promoter region． Conclusion IRF2BP2 protein affects the cell cycle and pro- liferation of AML cells by targeting and regulating MYC．

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.

Objective:To understand the knowledge, attitudes, and behaviors of residents in areas endemic for severe fever with thrombocytopenia syndrome (SFTS) and the factors influencing these aspects, to provide a scientific basis for the prevention and control of SFTS among residents in endemic areas.Methods:A multi-stage sampling method was used to select subjects for a questionnaire survey, and the collected data were analyzed and compared.Results:The awareness rate of SFTS-related knowledge among residents in the endemic areas of Qingdao was 14.38%, while the awareness rate of tick-related knowledge was 69.78%. The mean score for protective attitudes among residents in the endemic areas was 24.50±4.09, and the mean score for protective behaviors was 11.20±2.76. Among residents of different ages, occupations, and educational levels, comparisons of SFTS-related knowledge awareness rates ( χ2=293.553, P<0.001; χ2=495.216, P<0.001; χ2=677.272, P<0.001), tick-related knowledge awareness rates ( χ2=29.986, P<0.001; χ2=23.239, P=0.002; χ2=41.003, P<0.001), protective attitude scores ( H=52.094, P<0.001; H=33.446, P<0.001; H=81.715, P<0.001), and protective behavior scores ( H=52.344, P<0.001; H=28.465, P<0.001; H=67.061, P<0.001) showed statistically significant differences. Comparisons of these same factors among residents of different genders showed no statistically significant differences ( χ2=1.159, P=0.282; χ2=0.298, P=0.585; t=-0.808, P=0.419; t=-1.229, P=0.219). Comparisons of tick-related knowledge awareness rates among residents with different frequencies of outdoor work showed no statistically significant differences ( χ2=5.367, P=0.147); however, comparisons of SFTS-related knowledge awareness rates, protective attitude scores, and protective behavior scores among residents with different frequencies of outdoor work showed statistically significant differences ( χ2=117.010, P<0.001; F=4.127, P=0.006; H=56.280, P<0.001). Multivariate linear regression analysis revealed that older age, lower educational level, and less frequent outdoor work were associated with lower protective behavior scores ( t=-3.479, P<0.001; t=4.861, P<0.001; t=-7.753, P<0.001). Conclusions:Residents in the epidemic areas of SFTS have a low level of knowledge, attitude and practice. Factors influencing protective behaviors include age, occupation, educational level, and frequency of outdoor work. Farmers are a group that requires particular attention.

Objective:To study the learning curve in laparoscopic left lateral hepatic sectionectomy.Methods:The clinical data of 62 consecutive patients who underwent left lateral hepatic sectionectomy by a single operator from February 2015 to May 2022 in General Hospital of Northern Theater Command were retrospectively analyzed. There were 22 males and 40 females, with mean ±s.d. of (50.7±11.7) years. The learning curve was depicted and evaluated by using the cumulative summation test. The general information, operation and postoperative indicators of the growth level group and the master level group were compared.Results:The average operation time of the 62 consecutive subjects was (172.9±70.1) minutes. Intraoperative blood loss was 100 (50, 200) ml. Two patients were converted to open hepatectomy. Clavien-Dindo grade I postoperative complications occurred in 20 patients (32.3%), with grade Ⅱ in 1 patient (1.6%) and grade Ⅲb in another patient (1.6%). The learning curve reached its highest point on the 20th patient by using the cumulative summation test. The study subjects were then assigned into the growth level group (patient 1-20) and the master level group (patient 21-62). The master level group had a significantly wider spread of patient age [(52.9±11.0) years vs (46.1±11.9) years], decreased operation time [(146.8±55.6) min vs (227.9±66.7) min], shortened drainage tube removal time [4(3, 5) d vs 6(4, 7) d] and decreased postoperative hospital stay [5(5, 7) d vs 6.5(4, 9) d] (all P<0.05) when compared with the growth level group. Conclusion:Left lateral hepatic sectionectomy was safe and feasible, and a single operator went through a learning curve of 20 patients before he/she could master the operation more proficiently.

Objective:To investigate the clinical efficacy of laparoscopic hepatic caudate lobectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 5 patients with hepatic caudate lobe tumor who were admitted to the General Hospital of PLA Northern Theater Command from July 2018 to June 2021 were collected. There were 2 males and 3 females, aged 49(range, 26-55)years. All 5 patients underwent laparoscopic hepatic caudate lobectomy. Observation indicators: (1) intraoperative situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted using telephone interview or outpatient examination to detect tumor recurrence. The follow-up was up to March 2023. Measurement data with skewed distribution were represented as M(range) and count data were described as absolute numbers. Results:(1) Intraoperative situations. All 5 patients underwent laparoscopic hepatic caudate lobectomy with the left approach, including 3 cases receiving laparoscopic partial resection of hepatic caudate lobe, 1 case receiving laparoscopic partial resection of hepatic caudate lobe+left lateral lobectomy and 1 case receiving laparoscopic partial resection of hepatic caudate lobe+cholecystectomy. Intraoperative hilar occlusion was performed in 3 patients. The operation time and volume of intraoperative blood loss of 5 patients was 240(range, 180-370)minutes and150(range, 100-200)mL, respectively. (2) Postoperative situations. On the first day after surgery, the levels of albumin, alanine aminotransferase, and aspartate aminotransferase in 5 patients was 32.9(range, 29.2-40.3)g/L, 104.09(range, 57.11-1 018.67)U/L, and 67.13(range, 58.00-852.66)U/L, respectively. Three of 5 patients showed no significant changes in prothrombin time (PT) on the first day after surgery, while two patients did not undergo PT test. On the third day after surgery, the visual analogue score of 5 patients was mild pain. Among the 5 patients, 1 case had anal exhaust on the postoperative 1st day, and 4 cases had anal exhaust on the postoperative 2nd day. The time to drainage tube removal for 5 patients was 6(range, 4-10)days. There was no postoperative complication such as bleeding, infection, bile leakage or liver failure in 5 patients. Results of postoperative histopathological examination showed that 2 cases with adenoma, 2 cases with cavernous hemangioma and 1 case with smooth myolipoma. The duration of postoperative hospital stay of 5 patients was 6(range, 5-11)days. (3) Follow-up. All 5 patients were followed up for 22 (range, 19-51)months, and there was no tumor recurrence.Conclusion:It is safe and feasible to selectively carry out laparoscopic hepatic caudate lobectomy by strictly gras-ping the indications.

OBJECTIVE：To establish the method for the content det ermination of 4 components in Forsythia suspensa flowers by drying in shade ，vacuum freeze-drying ，oven（30，50，70 ℃）and sun ，so as to evaluate the effects of different drying methods on the main components of F. suspensa flowers and screen the optimal drying method. METHODS ：UPLC method was adopted. The determination was performed on Waters ACQUITY UPLC BEH C 18 column with mobile phase consisted of acetonitrile- 0.1％ phosphoric acid aqueous solution （gradient elution ）at the flow rate of 0.3 mL/min. The detection wavelength was set at 230 nm， and column was 35 ℃. The sample size was 1 μL. Euclidean closeness（C）i of different drying methods was calculated by TOPSIS comprehensive analysis method ，and the optimal drying method was defined. RESULTS ：The linear range of forsythiaside A ， rutin，forsythin，（+）-pinoresinol-4-O-β-D-glucopyranoside were 0.007 5-0.037 7，0.027 4-0.137 2，0.001 9-0.009 5，0.005 6-0.028 8 µg（all r＞0.999）. RSDs of precision ，stability（32 h）and reproducibility tests were all lower than 2％. The recoveries were 97.27％-102.53％，100.53％-104.11％，98.45％-104.02％，98.66％-104.82％，respectively；and all RSDs ＜3％（n＝3）. The contents were 1.645 8-4.987 9，11.730 2-20.978 0，0.875 5-2.005 0，2.366 0-5.535 7 mg/g. The content of forsythiaside A was the highest after drying at 30 ℃，rutin and （+）-pinoresinol-4- O-β-D-glucopyranoside were the highest after vacuum freeze-drying，forsythiaside was the highest after drying at 50 ℃ . Results of TOPSIS analysis showed that Ci of F. suspensa flowers by drying in shade ，vacuum freeze-drying ，oven（30，50，70 ℃）and sun were 0.079 9，0.553 5，0.495 4， 0.503 8，0.157 9，0.217 2，respectively；the order of Ci was vacuum freeze-drying ＞ 50 ℃ oven drying ＞ 30 ℃ oven drying＞sun drying ＞70 ℃ oven drying ＞ shade drying. CONCLUSIONS：Established method is simple ，reproducible and can be used for the content determination of 4 components in F. suspensa flowers. The samples are preferably dried by vacuum freeze-drying，followed by 50 ℃ oven drying ，30 ℃ oven drying ， and then dried in the sun and oven at 70 ℃ and finally in the shade.

Objective:To study the impact on dose accuracy for the treatment planning by manually assigning accurate electron density for CT image-based tumor tissues and organs at risk.Methods:Twenty cases of retrospective postoperative cervical cancer radiotherapy plans were selected. The body electron density of the corresponding organs was derived from the ICRU 46 report and assigned in the treatment planning system (Monaco5.11, Sweden), including the bladder, rectum, intestine, kidney, spinal cord, femoral head, and ilium. The original plans were double-arc volumetric modulated arc therapy plan (360° VMAT), using Monte Carlo algorithm, the calculation grid was 0.3 cm × 0.3 cm × 0.3 cm, and the minimum subfield width was 0.6 cm. Keep the original plan fluence unchanged and recalculate the dose to generate a new plan. The two-dimensional dose distribution and dose-volume histogram (DVH) were used to compare the differences between the two plans. The difference was compared between the two group plans by using the dosimetry parameters and DVH two dimension curve.Results:For the planning of assigning bulk electron density (Plan RED), the deviation of the patient′s target dose parameters and the original plan (Plan ref) was <2%, and the average deviation of all target regions D2, D98, Dmean was < 0.7%, only 2 of the 180 data were between 2% and 3%. The average deviation of V20, V30, D1 cm 3, Dmean of the bladder, rectum, and small intestine, the original Plan ref was less than 0.6%, and 4 out of 240 data had values > 2%. Plan RED′s average hop count was 0.9% higher than Plan ref, and the total number of subfields remains unchanged. The planned dose generated by manually assigning the electron density in Plan RED was higher than that in Plan ref, but met the clinical requirements. The two-dimensional curves of the DVH diagram for targets and OARs almost completely overlapped, and there was no obvious difference in the dose distribution diagram of the same cross section. The statistical result of all parameters showed that the difference in planned dose parameters between the two groups was not statistically significant( P>0.05). Conclusions:The overall deviation of dose accuracy between Plan RED and Plan ref is <2%, which meets the clinical requirements and provides a reference for realizing MRI-only treatment planning.