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.

OBJECTIVE To investigate the effects of triptolide （TP） exposure during pregnancy and lactation on the reproductive system development and function in male offspring of rats， providing a reference for medication safety during pregnancy and lactation. METHODS Pregnant rats were randomly divided into control group （12 rats， normal saline） and T1-T4 groups [12， 13， 14， 17 rats that received TP at 200， 400， 600， and 800 μg/（kg·d） respectively]. They were given relevant medicine/normal saline intragastrically， once a day， until the offspring were born and naturally weaned， the intragastric administration volume of each rat was consistently 2 mL. After 60 days of feeding， reproductive organ weights and coefficients were measured in male offspring， testicular and epididymal histology and sperm morphology were observed. Sperm motility， sperm count， and serum levels of gonadotropin-releasing hormone （GnRH）， follicle stimulating hormone （FSH）， luteinizing hormone （LH）， and testosterone （T） in the epididymides were analyzed. Protein expressions of glycogen synthase kinase 3α （GSK3α）， phosphorylated GSK3α （p-GSK3α）， and phosphatase 1γ2 （PP1γ2） in sperm were also determined. RESULTS Compared with the control group， the testicular and epididymal weights， serum levels of GnRH and T， the relative protein expression of PP1γ2 were significantly decreased in T1-T4 groups. Additionally， in the T2 to T4 groups， there were significant reductions in the weight and coefficient of the seminal vesicle， total number of sperm， sperm concentration， sperm motility as well as relative protein expressions of GSKα， p-GSK3α in the offspring rats. Furthermore， the epididymal coefficient in the T3 and T4 groups， the testicular coefficient， mean sperm track velocity and sperm curvature velocity in the T4 group were significantly decreased （P＜ 0.05）； the number of abnormal sperm， rate of sperm abnormality， and levels of FSH and LH in the offspring rats of the T1 to T4 groups were all significantly increased （P＜0.05）； in the offspring rats of the T1 to T4 groups， there was a decrease in the number of epithelial cells in the seminiferous tubules of the testes. Within the epididymal tissue， degenerative and necrotic changes in the epithelial cells were visible， accompanied by mild infiltration of inflammatory cells in the stroma. CONCLUSIONS TP exposure during pregnancy and lactation disrupts reproductive organ development， impairs spermatogenesis and sperm motility， as well as suppresses androgen synthesis in male offspring，thereby having a negative impact on the development of the reproductive system. These effects may be mechanistically linked to regulation of GSK3α， p-GSK3α and PP1γ2 protein expressions.

ObjectiveBased on literature data mining， this study explores the modeling elements of diarrhea-predominant irritable bowel syndrome （IBS-D） animal models in China and abroad， providing references and suggestions for improving modeling methods and evaluation indicators. MethodsRelevant literature on IBS-D animal experiments from 2014 to 2024 was retrieved through computer searches in databases such as China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， Chinese Medical Journals Full-text Database， and PubMed. Information on experimental animal species， gender， body weight， modeling methods， modeling periods， intervention controls， modeling standards， and detection indicators was organized. Microsoft Excel 2021 software was used to establish a database and perform statistical analysis to examine the characteristics of IBS-D animal models. ResultsA total of 398 articles that met the inclusion criteria were reviewed. The IBS-D animal models were predominantly established using SD rats， Wistar rats， and C57BL/6 mice. Male animals were more commonly used， with rats typically aged 6-8 weeks and mice aged 4-6 weeks. In terms of interventions， piverium bromide was the main Western medicine， Tongxieyaofang was the primary Chinese medicine， and electroacupuncture was the primary acupuncture method. Among the modeling methods， the multi-factor combined composite modeling approach was the most common. Modeling periods were mainly concentrated between 1-14 days and 15-30 days. The success criteria for modeling were mainly evaluated based on the animal's general condition， fecal appearance， visceral sensitivity， gastrointestinal motility， behavior， and pathology. Detection indicators included apparent indexes， pathological markers， biochemical indicators， oxidative stress， brain-gut peptides， neurotransmitters， inflammatory factors， immune function， intestinal permeability， autophagy， apoptosis， proteins related to relevant signaling pathways， intestinal microbiota and its metabolites， etc. ConclusionThere are various methods for establishing IBS-D animal models， but no unified and universally accepted method has been established. The operation of the same modeling methods and the evaluation standards of the models vary across studies. Based on the results of data mining， the authors suggest that the multi-factor combined composite modeling approach most closely reflects the pathophysiological processes of IBS-D， better simulating the complex clinical symptoms of IBS-D patients， such as abdominal pain and diarrhea， and has a high degree of clinical relevance. This method is relatively recommended. While animal models in general align with Western medicine standards， models incorporating traditional Chinese medicine （TCM） syndromes are relatively few. Therefore， one of the future directions for research is to establish IBS-D animal models that meet the combined clinical disease and syndrome requirements of both Western and Chinese medicine.

Objective: To prospectively evaluate the feasibility, accuracy, and safety of multiparameter MRI-guided percutaneous biopsy using a 1T open MRI scanner for evaluating suspicious centrally located lung lesions with associated post-obstructive atelectasis. Materials and Methods: In this single-center study, MRI-guided percutaneous coaxial cutting biopsy was performed for 107 suspicious central lung lesions with associated post-obstructive atelectasis in 107 patients between July 2015 and December 2020. A fast T2-weighted imaging (T2WI)-turbo spin echo (TSE) sequence and an enhanced fast T1-weighted imaging (T1WI)-TSE sequence were used to identify, localize, and biopsy lung lesions, and diffusion-weighted imaging (DWI) was used as a supplementary sequence for identifying the lesion location. The final diagnosis was confirmed by surgical histopathology or clinical follow-up for a minimum of 24 months. The sensitivity, specificity, and accuracy for diagnosing lung malignancies were calculated, and the complications were recorded for each case. Results: Using multiparameter MRI, central lung lesions could be clearly distinguished from post-obstructive atelectasis in 96 patients (89.7%). The sensitivity, specificity, and accuracy of MRI-guided percutaneous biopsy for diagnosing lung malignancy was 97.0% (98/101), 100% (6/6), and 97.2% (104/107), respectively. Self-limited hemoptysis occurred in three patients. Pneumothorax occurred in five patients, of which none required pleural drainage. No serious procedure-related complications were observed. Conclusion As a technology that does not involve ionizing radiation, multiparameter MRI-guided percutaneous coaxial cutting biopsy is a safe and accurate diagnostic technique for evaluating centrally located lung lesions associated with post-obstructive atelectasis.

Objective: To prospectively evaluate the feasibility, accuracy, and safety of multiparameter MRI-guided percutaneous biopsy using a 1T open MRI scanner for evaluating suspicious centrally located lung lesions with associated post-obstructive atelectasis. Materials and Methods: In this single-center study, MRI-guided percutaneous coaxial cutting biopsy was performed for 107 suspicious central lung lesions with associated post-obstructive atelectasis in 107 patients between July 2015 and December 2020. A fast T2-weighted imaging (T2WI)-turbo spin echo (TSE) sequence and an enhanced fast T1-weighted imaging (T1WI)-TSE sequence were used to identify, localize, and biopsy lung lesions, and diffusion-weighted imaging (DWI) was used as a supplementary sequence for identifying the lesion location. The final diagnosis was confirmed by surgical histopathology or clinical follow-up for a minimum of 24 months. The sensitivity, specificity, and accuracy for diagnosing lung malignancies were calculated, and the complications were recorded for each case. Results: Using multiparameter MRI, central lung lesions could be clearly distinguished from post-obstructive atelectasis in 96 patients (89.7%). The sensitivity, specificity, and accuracy of MRI-guided percutaneous biopsy for diagnosing lung malignancy was 97.0% (98/101), 100% (6/6), and 97.2% (104/107), respectively. Self-limited hemoptysis occurred in three patients. Pneumothorax occurred in five patients, of which none required pleural drainage. No serious procedure-related complications were observed. Conclusion As a technology that does not involve ionizing radiation, multiparameter MRI-guided percutaneous coaxial cutting biopsy is a safe and accurate diagnostic technique for evaluating centrally located lung lesions associated with post-obstructive atelectasis.

Objective: To prospectively evaluate the feasibility, accuracy, and safety of multiparameter MRI-guided percutaneous biopsy using a 1T open MRI scanner for evaluating suspicious centrally located lung lesions with associated post-obstructive atelectasis. Materials and Methods: In this single-center study, MRI-guided percutaneous coaxial cutting biopsy was performed for 107 suspicious central lung lesions with associated post-obstructive atelectasis in 107 patients between July 2015 and December 2020. A fast T2-weighted imaging (T2WI)-turbo spin echo (TSE) sequence and an enhanced fast T1-weighted imaging (T1WI)-TSE sequence were used to identify, localize, and biopsy lung lesions, and diffusion-weighted imaging (DWI) was used as a supplementary sequence for identifying the lesion location. The final diagnosis was confirmed by surgical histopathology or clinical follow-up for a minimum of 24 months. The sensitivity, specificity, and accuracy for diagnosing lung malignancies were calculated, and the complications were recorded for each case. Results: Using multiparameter MRI, central lung lesions could be clearly distinguished from post-obstructive atelectasis in 96 patients (89.7%). The sensitivity, specificity, and accuracy of MRI-guided percutaneous biopsy for diagnosing lung malignancy was 97.0% (98/101), 100% (6/6), and 97.2% (104/107), respectively. Self-limited hemoptysis occurred in three patients. Pneumothorax occurred in five patients, of which none required pleural drainage. No serious procedure-related complications were observed. Conclusion As a technology that does not involve ionizing radiation, multiparameter MRI-guided percutaneous coaxial cutting biopsy is a safe and accurate diagnostic technique for evaluating centrally located lung lesions associated with post-obstructive atelectasis.

Objective: To prospectively evaluate the feasibility, accuracy, and safety of multiparameter MRI-guided percutaneous biopsy using a 1T open MRI scanner for evaluating suspicious centrally located lung lesions with associated post-obstructive atelectasis. Materials and Methods: In this single-center study, MRI-guided percutaneous coaxial cutting biopsy was performed for 107 suspicious central lung lesions with associated post-obstructive atelectasis in 107 patients between July 2015 and December 2020. A fast T2-weighted imaging (T2WI)-turbo spin echo (TSE) sequence and an enhanced fast T1-weighted imaging (T1WI)-TSE sequence were used to identify, localize, and biopsy lung lesions, and diffusion-weighted imaging (DWI) was used as a supplementary sequence for identifying the lesion location. The final diagnosis was confirmed by surgical histopathology or clinical follow-up for a minimum of 24 months. The sensitivity, specificity, and accuracy for diagnosing lung malignancies were calculated, and the complications were recorded for each case. Results: Using multiparameter MRI, central lung lesions could be clearly distinguished from post-obstructive atelectasis in 96 patients (89.7%). The sensitivity, specificity, and accuracy of MRI-guided percutaneous biopsy for diagnosing lung malignancy was 97.0% (98/101), 100% (6/6), and 97.2% (104/107), respectively. Self-limited hemoptysis occurred in three patients. Pneumothorax occurred in five patients, of which none required pleural drainage. No serious procedure-related complications were observed. Conclusion As a technology that does not involve ionizing radiation, multiparameter MRI-guided percutaneous coaxial cutting biopsy is a safe and accurate diagnostic technique for evaluating centrally located lung lesions associated with post-obstructive atelectasis.

Objective: To prospectively evaluate the feasibility, accuracy, and safety of multiparameter MRI-guided percutaneous biopsy using a 1T open MRI scanner for evaluating suspicious centrally located lung lesions with associated post-obstructive atelectasis. Materials and Methods: In this single-center study, MRI-guided percutaneous coaxial cutting biopsy was performed for 107 suspicious central lung lesions with associated post-obstructive atelectasis in 107 patients between July 2015 and December 2020. A fast T2-weighted imaging (T2WI)-turbo spin echo (TSE) sequence and an enhanced fast T1-weighted imaging (T1WI)-TSE sequence were used to identify, localize, and biopsy lung lesions, and diffusion-weighted imaging (DWI) was used as a supplementary sequence for identifying the lesion location. The final diagnosis was confirmed by surgical histopathology or clinical follow-up for a minimum of 24 months. The sensitivity, specificity, and accuracy for diagnosing lung malignancies were calculated, and the complications were recorded for each case. Results: Using multiparameter MRI, central lung lesions could be clearly distinguished from post-obstructive atelectasis in 96 patients (89.7%). The sensitivity, specificity, and accuracy of MRI-guided percutaneous biopsy for diagnosing lung malignancy was 97.0% (98/101), 100% (6/6), and 97.2% (104/107), respectively. Self-limited hemoptysis occurred in three patients. Pneumothorax occurred in five patients, of which none required pleural drainage. No serious procedure-related complications were observed. Conclusion As a technology that does not involve ionizing radiation, multiparameter MRI-guided percutaneous coaxial cutting biopsy is a safe and accurate diagnostic technique for evaluating centrally located lung lesions associated with post-obstructive atelectasis.

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have emerged as critical agents for cancer therapy. By inhibiting the catalytic activity of PARP enzymes and trapping them in the DNA, PARPis disrupt DNA repair, ultimately leading to cell death, particularly in cancer cells with homologous recombination repair deficiencies, such as those harboring BRCA mutations. This review delves into the mechanisms of action of PARPis in anticancer treatments, including the inhibition of DNA repair, synthetic lethality, and replication stress. Furthermore, the clinical applications of PARPis in various cancers and their adverse effects as well as their combinations with other therapies and the mechanisms underlying resistance are summarized. This review provides comprehensive insights into the role and mechanisms of PARP and PARPis in DNA repair, with a particular focus on the potential of PARPi-based therapies in precision medicine for cancer treatment.
Humans ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Neoplasms/genetics* ; DNA Repair/drug effects* ; Animals ; Antineoplastic Agents/therapeutic use*