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.

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

Objective To observe the clinical efficacy of scalp acupuncture combined with repetitive transcranial magnetic stimulation in the treatment of patients with mild to moderate vascular dementia and to explore its potential mechanism of action.Methods A total of 102 patients diagnosed with mild to moderate vascular dementia who were treated in the outpatient and inpatient departments of Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from July 2021 to May 2023 were selected as the study subjects.The patients were randomly divided into an observation group and a control group using a random number table,with 51 patients in each group.The control group received repetitive transcranial magnetic stimulation treatment,while the observation group received scalp acupuncture therapy in addition to the treatment given to the control group.The treatment lasted for 16 weeks.After treatment,the clinical efficacy of the two groups was evaluated.Changes in the Mini-Mental State Examination(MMSE)scores,Montreal Cognitive Assessment(MoCA)scores,and traditional Chinese medicine(TCM)syndrome scores were observed before and after treatment.Additionally,serum levels of brain-derived neurotrophic factor(BDNF),vascular endothelial growth factor(VEGF),and homocysteine(Hcy)were measured.The cerebral blood flow velocities in the anterior,middle,and posterior arteries,as well as the levels of lipid peroxide(LPO),malondialdehyde(MDA),and superoxide dismutase(SOD),were compared between the two groups before and after treatment.The safety and incidence of adverse reactions in both groups were also evaluated.Results(1)After treatment,the MMSE and MoCA scores of both groups were significantly improved(P＜0.05),and the observation group showed significantly better improvement in MMSE and MoCA scores compared to the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the serum levels of BDNF,VEGF,and Hcy in both groups were significantly improved(P＜0.05),and the observation group showed significantly better improvement in these levels compared to the control group,with a statistically significant difference(P＜0.05).(3)After treatment,the cerebral blood flow velocities in the posterior,middle,and anterior arteries were significantly improved in both groups(P＜0.05),and the observation group showed significantly better improvement in these velocities compared to the control group,with a statistically significant difference(P＜0.05).(4)After treatment,the levels of LPO,MDA,and SOD were significantly improved in both groups(P＜0.05),and the observation group showed significantly better improvement in these levels compared to the control group,with a statistically significant difference(P＜0.05).(5)After treatment,the TCM syndrome scores improved significantly in both groups(P＜0.05),and the observation group showed significantly better improvement in these scores compared to the control group,with a statistically significant difference(P＜0.05).(6)The total effective rate in the observation group was 88.24%(45/51),while it was 70.59%(36/51)in the control group.The efficacy of the observation group was superior to that of the control group,with a statistically significant difference(P＜0.05).(7)The incidence of adverse reactions in the observation group was 3.92%(2/51),while it was 1.96%(1/51)in the control group.There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Scalp acupuncture combined with repetitive transcranial magnetic stimulation in the treatment of mild to moderate vascular dementia helps regulate cerebral hemodynamics and neurotrophic factor expression,improves cognitive function,and demonstrates significant efficacy with good safety.

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Objective:To investigate the long-term efficacy, safety and prognostic factors of intraoperative radiotherapy (IORT) for narrow-margin (resection margin < 1 cm) hepatectomy in patients with hepatocellular carcinoma (HCC) during radical surgery.Methods:A retrospective cohort study was conducted. The data of primary HCC patients undergoing radical surgery and narrow-margin hepatectomy IORT in the Cancer Hospital of the Chinese Academy of Medical Sciences from November 2009 to February 2019 were collected. IORT applied 6 MeV or 9 MeV electron beams and a single irradiation was given to the margin. Kaplan-Meier method was used for the overall survival (OS) and disease-free survival (DFS) analysis; log-rank test was used for survival comparison among subgroups. The recurrence patterns and adverse reactions were recorded. Univariate and multivariate Cox proportional hazards models were used to analyze the factors influencing the OS and DFS.Results:A total of 64 patients were enrolled, with the median age [ M ( Q1, Q3)] of 57 years (49, 63) years. All patients included 55 males (85.9%) and 9 females (14.1%). The median dose of IORT was 15 Gy (range: 12-17 Gy). The median follow-up time was 83.3 (64.4, 91.9) months. The 1-year, 3-year, 5-year, 7-year, 10-year OS rates were 90.4%, 80.6%, 75.5%, 71.4% and 47.6%, respectively; the 1-year, 3-year, 5-year, 7-year,10-year DFS rates were 77.8%, 68.1%, 59.6%, 57.6% and 38.4%, respectively. Univariate Cox regression analysis indicated that preoperative serum alpha-fetoprotein (AFP) > 400 ng/ml was an independent risk factor for poor OS (> 400 ng/ml vs. ≤ 400 ng/ml: HR = 6.57, 95% CI: 2.16-19.96, P < 0.001), while not the independent influencing factor of poor DFS ( HR = 1.71, 95% CI: 0.65-4.52, P = 0.277). The age ≤ 60 years or not, gender, viral hepatitis or not, American Joint Committee on Cancer stage, tumor diameter (> 5 cm or not), tumor number, degree of tumor differentiation, microvascular invasion or not, microsatellite nodules or not, anatomical liver resection or not, and the dose of IORT ≤15 Gy or not were not the independent influencing factors of poor OS and DFS (all P > 0.05). Kaplan-Meier method analysis showed that patients with preoperative serum AFP ≤ 400 ng/ml (48 cases) had better OS compared with those with preoperative serum AFP>400 ng/ml (16 cases) (5-year OS rate: 84.8% vs. 44.9%; 7-year OS rate: 79.9% vs.37.4%), and the difference was statistically significant ( P = 0.002). There was no statistically significant difference in the DFS between the 2 groups ( P = 0.134). During the follow-up, 28 patients (43.8%) relapsed, including 17 cases (26.6%) of early recurrence and 11 cases (17.2%) of late recurrence. No marginal recurrence was observed. There were 22 cases (34.4%) of intrahepatic recurrence alone, 2 cases (3.1%) of extrahepatic recurrence and 4 cases (6.3%) of stimutaneous recurrence inside and outside the liver. The 1-, 3-, 5- and 7-year cumulative recurrence rates inside the liver were 19.0%, 27.2%, 37.4% and 39.3% respectively, and the cumulative recurrence rates outside the liver were 6.4%, 8.0%, 9.6% and 9.6% respectively. There were no adverse reactions above grade 3 in the entire group. There were no surgery-related deaths within 30 d after the operation, and no radiation-induced liver disease occurred. Conclusions:Narrow-margin IORT helps HCC patients receiving hepatectomy to achieve favorable long-term survival and adverse reactions are tolerable. It can be used as a safe and effective adjuvant therapy alternative.

Objective:To explore the application effect of a hierarchical training model based on the "geese formation effect" in the professional training of gastrointestinal center nurses.Methods:A total of 122 nurses at the Gastrointestinal Center of West China Hospital, Sichuan University, were randomly divided into an experimental group ( n=61) and a control group ( n=61). The experimental group received a hierarchical training model based on the "geese formation effect". Nurses in this group were divided into four levels of N1 to N4 according to seniority, corresponding to the roles of "young geese", "growing geese", "flying geese", and "leading geese/flying geese", and differentiated training content and formats were implemented. The control group received routine training. At the end of the training and at 3 and 6 months after the training, theoretical knowledge and operational skills were assessed, along with evaluations of job competency, professional characteristic indicators, and teaching satisfaction. The chi-square test and independent samples t-test were performed using SPSS 25.0. Results:At the end of the training and at 3 and 6 months after the training, compared with the control group, the experimental group achieved significantly higher scores in theoretical knowledge [(91.69±3.04) vs. (83.66±6.35), (89.42±3.29) vs. (81.33±5.79), (85.63±3.67) vs. (76.59±6.48)] and operational skills [(92.20±2.54) vs. (82.95±6.09), (90.15±2.83) vs. (81.61±5.47), (89.24±3.18) vs. (78.91±5.89)] (all P<0.001). The total score of job competency in the experimental group was higher than that in the control group. For the professional characteristic indicators, the experimental group also outperformed the control group in the implementation rate of postoperative pressure ulcer prevention (90.16% vs. 72.13%) and the ERAS compliance rate (93.44% vs. 80.33%) (both P<0.05). The total score of training satisfaction was higher in the experimental group than in the control group. Conclusions:The hierarchical training model based on the "geese formation effect" can effectively improve the theoretical knowledge, operational skills, job competency, and clinical nursing quality of nurses, with high teaching satisfaction and promotion value.

Objective : To analyze the epidemiological characteristics of tuberculosis in Urumqi and assess the im⁃pact of the national health examination policy , as well as COVID⁃19 prevention and control measures , on tuberculo⁃sis incidence in Xinjiang. Methods: The seasonal patterns of pulmonary tuberculosis were examined using the seasonal index method and circular distribution analysis. An Interrupted Time Series (ITS , Interrupted Time Series) model was employed to investigate how the national health examination policy and COVID_19 interventions influenced trends in tuberculosis incidence in Urumqi. Results: From 2013 to 2021 , a total of 19 ,049 cases of tuberculosis were reported in Urumqi. The peak incidence day occurred on May 25th , indicating a consistently high rate throughout the year, particularly during spring and summer months. The results of the interrupted time series model indicated that the initial monthly incidence rate of pulmonary tuberculosis in Urumqi was 5. 05 per 100 ,000. From January 2013 to September 2016 , the incidence rate of pulmonary tuberculosis showed a slow upward trend , and the upward trend was significant (β1 = 0. 039 ,P < 0. 05) . After the implementation of the universal health checkup policy , the incidence rate of pulmonary tuberculosis showed a slow downward trend , and the downward trend was significant(β3 = - 0. 109 ,P < 0. 05) . After the outbreak of the COVID_19 epidemic in January 2020 , the incidence rate of pulmonary tuberculosis in Urumqi first dropped rapidly and then entered a slow upward stage , and the upward trend was significant(β5 = 0. 082 , P < 0. 05) . Conclusion It is recommended that public health authorities prioritize timely identification of potential TB patients during periods with elevated incidence rates observed in spring and summer months. While significant progress has been made through implementing national health examinations policies , attention must be directed towards understanding how ongoing epidemics affect TB patient detection. Thus , enhancing surveillance efforts and intervention strategies are essential in adapting to this new normal. Key words tuberculosis ; seasonal index method ; circular distribution method ; national health examination ; COVID_19 ; interruption time series

Objective:To evaluate the short-and medium-term therapeutic efficacy of shockwave balloon therapy for TASCⅡ C/D femoropopliteal artery atherosclerosis obliteration.Methods:This retrospective cohort study included 25 patients who received shockwave balloon therapy in five vascular centers from August 2022 to June 2023. All patients were diagnosed with TASC Ⅱ C/D femoropopliteal arteriosclerosis obliterans (13 cases of type C and 12 cases of type D), and underwent intravascular shock wave lithotripsy (IVL) to treat calcified lesions. The immediate effectiveness (residual stenosis<30% and no flow-limiting dissection), safety (whether there were adverse vascular events during the operation) and the rate of salvage stent implantation were recorded. The observation indexes of patients before operation, early postoperative period (immediately after operation or before discharge) and postoperative follow-up period (3, 6, 12 months after operation) were collected. The observation indexes included ankle-brachial index (ABI), Rutherford classification, and minimum lumen diameter (MLD). Repeated measures ANOVA was used to evaluate the changes of observation indexes in the early postoperative and follow-up stages compared with those before operation; Kaplan-Meier survival analysis was used to evaluate the one-stage patency rate at follow-up and the target lesion revascularization rate free from clinical drive.Results:The immediate effectiveness of surgery was 100% in all patients, with no vascular related adverse events occurred, and no remedial stent implantation was performed. The ABI, Rutherford grade and MLD of the patients in the early postoperative period and each follow-up stage were improved compared with those before operation, with statistically significant differences ( P<0.05). Kaplan-Meier survival analysis showed that the primary patency rate at 12 months after surgery was 0.78 (95% CI 0.64-0.84), and the revascularization rate of target lesions free from clinical drive was 0.87 (95% CI 0.85-0.95). Conclusion:Shockwave balloon therapy for complex calcified femoropopliteal artery lesions is safe and reliable, with satisfactory short-and medium-term efficacy.

Objective To compare the value of standard deviation(SD)method and root mean square(RMS)method for measuring signal-to-noise ratio(SNR)of MRI of American College of Radiology(ACR)phantom based on phased array coils.Methods ACR phantom was scanned with head coil(Head),abdominal coil(Anterior),dual piece flexible coil(Flex L)and abdominal coil+flexible coil(Anterior+Flex L)each for 6 times,respectively,with sequences of axial T 1W-spin echo(SE)and T2W-SE.And the scanning schemes were divided into 8 groups based on 4 types of coils and 2 sequences.SNR of 8 groups were measured with standard deviation method and root mean square method,respectively,and the differences between the above 2 methods were observed.Results For T1W-SE sequence,SNRsD of MRI based on Head,Anterior,Flex L and Anterior+Flex L was 1.25±0.07,0.56±0.02,1.15±0.10 and 1.04±0.11,respectively,while SNRRMs was 1.10±0.07,0.58±0.03,1.01±0.13 and 1.31±0.15,respectively.For T2W-SE sequence,SNRsD was 1.40±0.08,0.48±0.02,1.04±0.07 and 1.08±0.06,respectively,while SNRRMs was 1.29±0.09,0.53±0.03,0.84±0.08 and 1.35±0.12,respectively.Compared pairwise,significant difference of SNRsD was found in 9 pairs(all P＜0.05),while of SNRRMs was detected in 10 pairs(all P＜0.05).Conclusion Compared with standard deviation method,root mean square method was more suitable for measuring SNR of MRI of ACR phantom based on phased array coils.

[Objective]To study the application effect of the"Learning-Skill-Application"teaching method on enhancing the specialized abilities of resident doctors in residence training.[Methods]A total of 140 resident doctors in residence training who rotated in the Acupuncture and Tuina Department of Jiaxing Hospital of Traditional Chinese Medicine from July 2022 to December 2023 were included and divided into two groups by random number table method.The control group was taught traditionally,and the observation group was taught using the"Learning-Skill-Application"guided teaching method.After the rotation,the resident doctors in residence training were evaluated in multiple dimensions,including basic knowledge,clinical skills and clinical consultation ability(such as medical history collection and physical examination,clinical thinking of traditional Chinese and western medicine,medical records writing).The questionnaire survey was concurrently administered to assess resident doctors'satisfaction with the teaching performance of their clinical instructors.[Results]The observation group demonstrated superior performance in both theoretical basic knowledge exam scores and clinical skills operation scores compared with the control group(P<0.05).Additionally,the observation group exhibited better clinical consultation abilities(P<0.05)and reported higher satisfaction with the teaching methodology than the control group(P<0.05).[Conclusion]In the standardized training of Department of Acupuncture and Moxibustion and Department of Tuina,the"Learning-Skill-Application"guided teaching method is better than the traditional teaching method in improving the specialized ability of resident doctors in residence training,and is worth promoting.