Objective To summarize and analyze the efficacy and influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia relapsing after the first allo-HSCT. Methods Clinical data of 17 patients with acute leukemia who underwent second allo-HSCT at Peking University First Hospital from January 2005 to December 2024 were retrospectively analyzed. Results Among the 17 patients, 7 achieved long-term disease-free survival after second transplantation. The median progression-free survival after successful second transplantation was 7 months (range 8 days to 69 months). The relapse fatality was 24%, and the transplant-related fatality was 35%. Conclusions Second transplantation is an effective treatment for relapsed and refractory acute leukemia, but the relapse fatality and transplant-related fatality remain high. Patient age, time of relapse after the first transplantation and disease status before second transplantation are all factors that affect the efficacy of second transplantation. Younger age, late relapse and complete remission of disease before second transplantation are all beneficial for long-term disease-free survival after second transplantation.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Objective:To compare the value of different imaging modalities in evaluating early efficacy of 90Y-selective internal radiation therapy (SIRT) for liver malignant tumors. Methods:From September 2021 to December 2023, a retrospective analysis was conducted on 43 patients (32 males, 11 females; age (55.8±14.7) years) with liver malignant tumors who received 90Y-SIRT at Hainan Cancer Hospital and Boao Super Hospital. The injection dosage of 90Y was 1.5(1.2, 2.4)GBq. Clinical and imaging data of patients before and after treatment for multimodal evaluation were collected, including MRI plain and enhanced scans, as well as diffusion weighted imaging (DWI). Plain scan images were evaluated for the treatment efficacy by response evaluation criteria in solid tumors (RECIST) 1.1 version, while enhanced MRI was scored into 1-5 based on changes in the target area, including increased low-density range, necrotic features, and decreased enhancement. The minimum apparent diffusion coefficient (ADC min) of DWI increased by 20% compared to baseline was determined to be responsive. Wilcoxon signed rank test was used to analyze data, and ROC curve analysis was used to analyze the diagnostic efficacy of different imaging modalities (Delong test). Results:All patients had baseline MRI data, 39 underwent MRI at 1-month after treatment, and 22 underwent MRI at 3-month after treatment. Based on MRI plain scan images, the target lesions showed partial remission (PR) in 10.26%(4/39) of patients, progressive disease (PD) in 5.13%(2/39) of patients, and stable disease (SD) in 84.61%(33/39) of patients at 1-month after treatment; while there were 40.91%(9/22) PR, 9.09%(2/22) PD and 50.00%(11/22) SD at 3-month after treatment. Based on DWI images, 35.90%(14/39) and 68.18%(15/22) of patients were considered responsive at 1-month and 3-month after treatment, respectively. Compared with baseline, the differences of tumor sizes, enhancement degree of target lesions and ADC min at 1-month and 3-month after treatment were statistically significant ( Z values: from -3.88 to -2.39, all P<0.05). Compared with the tumor size and enhancement degree, the AUCs of ADC min were the highest at 1-month (0.701) and 3-month (0.953) after treatment ( Z values: 0.40-2.29, all P<0.05). Conclusions:MRI plain scan, MRI enhancement and DWI are effective in the evaluation the efficacy of 90Y-SIRT for liver malignant tumors at 1-month and 3-month after treatment. ADC min is superior to tumor size and enhancement degree in diagnostic efficacy.

Objective To investigate the effects of Zhuang medicinal thread moxibustion on apoptosis of interstitial cells of Cajal(ICC)in gastric smooth muscle of diabetic gastroparesis(DGP)rats via regulation of the p38MAPK signaling pathway.Methods Totally 60 rats were randomly divided into a blank group(10 rats)and a modeling group(50 rats).DGP models were established in the modeling group via intraperitoneal injection of streptozotocin.50 successfully modeled rats were further randomized into model group,Western medication group,prevention+treatment group,prevention group and treatment group,with 10 rats in each group.The Western medication group was administered mosapride citrate by gavage for 3 weeks starting at week 10;the prevention+treatment group underwent Zhuang medicinal thread moxibustion("Zhongwan",bilateral"Neiguan"and"Zusanli")intervention for 6 weeks starting at week 7;the prevention group received Zhuang medicinal thread moxibustion for 3 weeks starting at week 7;and the treatment group received Zhuang medicinal thread moxibustion for 3 weeks starting at week 10,3 cones per point,once a day;the blank group and model group received handling only.The random blood glucose and body mass of rats were detected,and the gastric emptying rate and intestinal propulsion rate were calculated.HE staining was used to observe the morphology of gastric smooth muscle tissue,TUNEL staining was used to detect the apoptosis of gastric smooth muscle tissue,ELISA was used to detect the contents of Caspase-3,TNF-α,IL-1β and IL-6 in gastric smooth muscle tissue,immunohistochemistry was used to detect the positive expressions of Cx43 and c-kit in gastric smooth muscle tissue,Western blot was used to detect the expressions of p38MAPK,p-p38MAPK,BAX and Bcl-2 protein in gastric smooth muscle tissue.Results Compared with the blank group,the random blood glucose significantly increased in the model group(P<0.01),and the body mass,gastric emptying rate and small intestinal propulsion rate significantly decreased(P<0.01),the blood vessels of gastric tissue were not clear,the surface was not smooth,the mucosal folds were less,the arrangement of gastric smooth muscle cells was disordered,the nuclear membrane was not clear,and there were vacuole like changes between cells,the apoptosis rate significantly increased(P<0.01),the contents of Caspase-3,TNF-α,IL-1β,IL-6 and the protein expressions of p38MAPK,p-p38MAPK and BAX in gastric smooth muscle tissue significantly increased(P<0.01),and the positive expressions of Cx43,c-kit,the protein expression of Bcl-2 and Bcl-2/BAX ratio significantly decreased(P<0.01).Compared with the model group,the random blood glucose of rats in each intervention group decreased,and the body mass,gastric emptying rate and intestinal propulsion rate increased(P<0.01),the blood vessels of gastric tissue were clear,the inner surface of stomach was smooth,the mucosal folds were not rich,no ulcer was found,the shape of gastric smooth muscle cells was complete,the nuclear membrane was clear,and the arrangement of muscle cells was regular,the apoptosis rate significantly decreased(P<0.01),the contents of Caspase-3,TNF-α,IL-1β,IL-6 and the expressions of p38MAPK,p-p38MAPK,BAX protein in gastric smooth muscle tissue decreased(P<0.05,P<0.01),the positive expressions of Cx43,c-kit,the protein expression of Bcl-2 and Bcl-2/BAX ratio increased(P<0.05,P<0.01).The overall effect of the prevention+treatment group was better than that of the Western medication group,prevention group and treatment group(P<0.05,P<0.01).Conclusion Zhuang medicinal thread moxibustion may reduce gastric inflammation and ICC apoptosis in DGP rats by inhibiting p38MAPK signaling pathway,so as to improve DGP gastric motility disorder,and the effect of early intervention is more significant.

Renal metastasis from differentiated thyroid cancer (DTC) is uncommon and is hard to be distinguished from primary renal cell carcinoma. There is no consensus on diagnosis and treatment, and decisions about surgery and 131I therapy doses usually depend on experience. To better understand clinical characteristics and current treatment status, this study systematically reviews existing studies, exploring epidemiological features, clinical symptoms, imaging findings (including lesions characteristics across various imaging modalities), therapeutic strategies, and prognosis of DTC renal metastases, providing evidence-based references for clinical practice.

Objective:To investigate the clinicopathological characteristics, molecular features, differential diagnosis and prognosis of renal cell carcinoma (RCC) with TFEB gene amplification.Methods:A total of 113 cases of unclassified RCCs and RCCs with TFEB positive expression were collected from the Affiliated Hospital of Qingdao University and Navy 971 Hospital from January 2010 to December 2024. Eight cases of RCCs with TFEB amplification were identified using tissue microarrays, immunohistochemistry, and fluorescence in situ hybridization (FISH) techniques. The clinicopathological data and prognosis of the 8 cases were summarized, and relevant literature was reviewed.Results:Among the 8 cases, there were 5 males and 3 females. The average age was 63.4 (54, 77) year and the median age was 63.5 (59.0, 65.5) year. Seven cases were detected through physical examination, and 1 case presented with initial symptoms of metastasis to bones and lungs. The cohort included 1 biopsy specimen and 7 surgical resection specimens. The tumor diameters ranged from 2.5 to 15.0 cm. The cut surfaces of 5 cases were grayish-yellow or grayish-red, and 2 cases exhibited a colorful appearance, among which 3 cases involved renal sinus and 1 case showed invasion of the perirenal fat tissue. Microscopically, 4 cases were composed of clear cells arranged in solid sheets or acinar structures, along with varying numbers of eosinophilic cells. Two cases exhibited the morphology of high-grade eosinophilic RCC, and 1 case presented biphasic morphology with diffuse polygonal eosinophilic tumor cells and dense small cell components. The remaining 1 case exhibited the morphology of clear cell RCC. According to the WHO/ISUP nuclear grading system, 6 cases were Grade 3 and 2 cases were Grade 2. Multifocal necrosis was observed in 4 cases. In 4 surgical specimens, the tumor tissue invaded the renal parenchyma, with 2 cases showing nodular infiltration to surrounding tissues and 1 case with intravascular tumor thrombus. Immunohistochemical results showed varying degrees of TFEB nuclear positivity in 6 cases (6/8). Melanocytic markers such as Melan A (5/8) and HMB45 (3/8) were expressed at varying degrees. Cathepsin K (6/8), GPNMB (6/8), P504s (7/8) and CD10 (7/8) were positively expressed in most cases. FISH results revealed high-copy amplification of TFEB gene in 4 cases (partially showing clustered amplification) and low-copy amplification in 4 cases. During the follow-up period of 3 to 64 months of the 8 cases, 3 cases metastasized and 2 cases died of disease (both with high-copy TFEB gene amplification).Conclusions:RCC with TFEB gene amplification is rare and exhibits diverse morphological features. A common morphological characteristic of this type of tumor is a mixture of sheet-like clear cells and high nuclear grade eosinophilic cells. Combined immunohistochemical staining for TFEB, melanocytic markers, and GPNMB is helpful for the diagnosis of the tumor, and FISH detection of TFEB gene amplification is the most definitive method in diagnosing this tumor. RCC with TFEB gene amplification usually presents with strong aggressiveness and poor prognosis. Combining surgical resection with immunotherapy or VEGFR-targeted drugs might have therapeutic effects on the tumor.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective To elucidate the causal relationship between specific immune cells and autoimmune hepatitis(AIH)using a two-sample Mendelian randomization(MR)approach.Methods A bidirectional MR analysis was conducted using data from large publicly accessible Genome-Wide Association Study(GWAS)databases.The inverse variance weighted(IVW)method was employed as the primary method to evaluate the relationship between 731 immune cell traits and AIH.The false discovery rate(FDR)was controlled using the Benjamini-Hochberg correction.Additionally,pleiotropy and heterogeneity tests were performed,and a leave-one-out sensitivity analysis was conducted to further validate the robustness of the results.Results At a significance level of 0.20,it was found that the absolute count of CD28-CD8+regulatory T-cells(IVW:odds ratio[OR]=1.486;95％confidence interval[CI],1.189-1.859;P＜0.001;PFDR=0.185),the level of CD28 on CD39+secreting regulatory T-cells(IVW:OR=1.194;95％CI,1.074-1.328;P=0.001;PFDR=0.185),and the level of CD45 on mononuclear myeloid-derived suppressor cells(IVW:OR=1.243;95％CI,1.108-1.394;P＜0.001;PFDR=0.143)were associated with an increased risk of AIH.The level of programmed death-ligand 1 on CD14+CD16+monocytes(IVW:OR=0.849;95％CI,0.771-0.935;P＜0.001;PFDR=0.185)was associated with a reduced risk of AIH.Conclusion Four immune cell phenotypes associated with AIH risk are identified.Further investigation is needed to validate these findings and explore new therapeutic avenues.