Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.

An 8-year-old male child with acute lymphoblastic leukemia(ALL)developed signs of methotrexate(MTX)toxicity—such as vomiting,chest tightness,and rapidly elevated serum creatinine and uric acid levels—on the second day after his first high-dose methotrexate(HD-MTX)treatment.The toxicity is considered due to delayed excretion of methotrexate.The clinical pharmacist assisted the medical team in formulating a treatment plan that included adequate hydration and alkalinization,leucovorin rescue,and subsequent dose adjustment of MTX,based on therapeutic drug monitoring and pharmacogenetic testing results.By day 11,the patient's MTX plasma concentration,serum creatinine,and uric acid levels had returned to safe ranges.In this case,the clinical pharmacists used pharmaceutical knowledge to analyze potential factors contributing to delayed MTX elimination,and assisted the treatment team to improve the safety and efficacy of drug therapy.This case provides valuable experience for the standardized management of similar pediatric patients.

Objective:This study analyzed the clinical characteristics and early mortality risk factors in patients with hyperleukocytic acute leukemia (HAL) to provide a basis for predicting early prognosis.Methods:Data were retrospectively collected from 211 patients with primary HAL who visited the Emergency Center of the Hematology Hospital, Chinese Academy of Medical Sciences, between July 1, 2019 and November 30, 2021. The value of each indicator in early risk stratification and prognosis was analyzed.Results:The early-death group exhibited higher WBC, peripheral blood immature cell proportions, prothrombin times (PT), fibrinogen degradation products (FDP), and D-dimer levels than the non-early death group ( P<0.05). Mortality in hyperleukocytic AML (20.5% ) was significantly higher than that in hyperleukocytic ALL (9.3% ) ( P<0.05). There were significant differences in age, creatinine, PT, fibrinogen (FIB) levels, WBC, lactic dehydrogenase (LDH), uric acid, blood potassium, blood calcium, and blood phosphorus levels between the two groups of patients ( P<0.05). A WBC threshold of 255.96×10?/L predicted early mortality with 65.6% sensitivity and 69.0% specificity, with higher WBC levels associated with a 5.164-fold increased mortality risk ( P<0.05). The age, WBC, LDH, urea, PT, FDP and D-dimer of patients at the time of consultation are risk factors affecting the survival of HAL ( P<0.05) . Conclusion:HAL is a life-threatening condition with a high early mortality. Age, WBC, LDH, urea, PT, FDP and D-dimer are risk factors for early death in HAL.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To compare the efficacy of biplanar fixation combined with bone grafting and proximal femoral nail anti-rotation (PFNA) in the treatment of critically complicated osteoporotic intertrochanteric femoral fracture .Methods:A retrospective cohort study was conducted to analyze the clinical data of 28 patients with critically complicated osteoporotic intertrochanteric femoral fracture, admitted to Union Hospital, Tongji Medical College of Huazhong University of Science and Technology from January 2020 and December 2022, including 3 males and 25 females, aged 70-91 years [(79.4±6.3)years]. T score for bone mineral density was -2.5~-4.1 SD［（-3.3±0.6）SD］. All the patients were found with type A2.2-A3.3 fracture based on AO classification, and were complicated with trochanteric lateral wall fracture. Among them, 16 patients underwent biplanar fixation combined with bone grafting (biplanar fixation group), while 12 underwent PFNA internal fixation (PFNA group). All the patients received anti-osteoporosis therapy after surgery. The two groups were compared in terms of the operative time, intraoperative blood loss, hemoglobin levels at 3 days postoperatively, and time to weight-bearing. The visual analogue scale (VAS) scores and Harris hip scores at 1, 3, 6 months postoperatively, and at the last follow-up and the incidence of complications were also detected in the two groups.Results:All the patients were followed up for 12-16 months [(14.1±1.4)months]. In the biplanar fixation group, the operative time was (75.1±15.3)minutes, significantly longer than (45.6±14.2)minutes in the PFNA group ( P<0.01); the intraoperative blood loss was (234.1±11.8)ml, significantly more than (170.0±13.4)ml in the PFNA group ( P<0.01); the hemoglobin level at 3 days postoperatively was (82.6±9.3)g/L in the biplanar fixation group, higher than (64.8±6.8)g/L in the PFNA group ( P<0.01). The time to weight-bearing was (1.1±0.7)weeks in the biplanar fixation group, significantly shorter than (3.2±1.2)weeks in the PFNA group ( P<0.01). There were no statistically significant differences between the two groups in VAS scores and Harris hip scores at 1, 3, 6 months postoperatively, and at the last follow-up ( P>0.05). The VAS scores and Harris hip scores in the two groups were gradually improved with the prolongation of postoperative time ( P<0.05 or 0.01). No complications such as neurovascular injuries were observed in either group. One patient in the biplanar fixation group developed lower extremity deep vein thrombosis (DVT), with a complication rate of 6.3%, while 2 patients in the PFNA group developed lower extremity DVT and 4 hypostatic pneumonia, with a complication rate of 50.0% ( P<0.05). Conclusion:Compared with PFNA internal fixation, biplanar fixation with bone grafting has the advantages of less postoperative blood loss, earlier weight-bearing exercises and lower incidence of complications in the treatment of critically complicated osteoporotic intertrochanteric femoral fracture, despite longer operative time and more intraoperative blood loss.

Venetoclax (Ven) is now widely used for both acute myeloid leukaemia (AML) and high-risk myelodysplastic syndrome (MDS), yet there is no consensus on salvage regimens after Ven failure. This study retrospectively evaluated the efficacy and safety of selinexor combined with subcutaneous decitabine (DAC) in 10 patients with AML or MDS with excess blasts (MDS-EB1/2) who had experienced prior Ven treatment failure. A literature review was also performed. Among the 7 patients with AML, 1 achieved complete remission (CR), 2 achieved CR with incomplete hematologic recovery (CRi), 1 achieved partial remission (PR), 2 had no remission, and 1 experienced disease progression (PD). Among the 3 patients with MDS, 2 achieved marrow CR and 1 had stable disease (SD). The median duration of response among the 6 responding patients was 2 months (range, 0.5-6 months). All 10 patients experienced varying degrees of myelosuppression. Five patients had mild gastrointestinal reactions, all of which were manageable. The overall tolerability was good, and no treatment-related deaths occurred. These findings suggest that selinexor combined with subcutaneous decitabine offers a novel and well-tolerated therapeutic option for patients with myeloid malignancies who have previously failed venetoclax-based therapy.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective To investigate the predictive value of four thrombotic markers[thrombin-antithrombin complex(TAT),tissue-type plasminogen activator-plasminogen activator inhibitor-1 complex(t-PAIC),plasmin-α2-plasmin inhibitor complex(PIC)and thrombomodulin(TM)]for short-term prognosis of patients with acute leukemia complicated by disseminated intravascular coagu-lation(DIC).Methods A prospective cohort study was conducted.Fifty-two patients with acute leukemia complicated by DIC were selected as study group,and 50 patients with simple acute leuke-mia were selected as control group.The general data and levels of the four thrombotic markers(PIC,TAT,TM,t-PAIC)were compared between the two groups.The Kaplan-Meier(KM)survival curve was plotted to analyze the 28-day prognosis of the patients in the study group.The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of the four thrombotic markers for poor short-term prognosis in patients with acute leukemia complicated by DIC.Results The plas-ma levels of TAT,PIC,t-PAIC and TM in the study group were higher than those in the control group,and the differences were statistically significant(P＜0.05).Among the patients in the study group,there were 17 deaths(poor prognosis)and 35 survival cases(good prognosis)at 28 days.The plas-ma levels of TAT,PIC,t-PAIC and TM in patients with poor prognosis were higher than those in pa-tients with good prognosis at admission,and the differences were statistically significant(P＜0.05).The ROC curve showed that the area under the curve(AUC)for TAT,PIC,t-PAIC,and TM in predicting poor short-term prognosis in patients with acute leukemia complicated by DIC alone were 0.775,0.769,0.767,and 0.770,respectively.The AUC for the combined prediction of the four thrombotic markers was 0.939,which was higher than that for each individual marker(Z=1.986,2.014,2.026,2.003;P=0.021,0.010,0.008,0.014).Conclusion The four thrombotic markers(TAT,PIC,t-PAIC,TM)have a high predictive value for the short-term prog-nosis of patients with acute leukemia complicated by DIC.Combined detection can provide a refer-ence basis for clinical prognosis prediction in these patients.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, with few effective treatments currently available. The multifactorial nature of AD, shaped by genetic, environmental, and biological factors, complicates both research and clinical management. Recent advances in artificial intelligence (AI) and multi-omics technologies provide new opportunities to elucidate the molecular mechanisms of AD and identify early biomarkers for diagnosis and prognosis. AI-driven approaches such as machine learning, deep learning, and network-based models have enabled the integration of large-scale genomic, transcriptomic, proteomic, metabolomic, and microbiomic datasets. These efforts have facilitated the discovery of novel molecular signatures and therapeutic targets. Methods including deep belief networks and joint deep semi-non-negative matrix factorization have contributed to improvements in disease classification and patient stratification. However, ongoing challenges remain. These include data heterogeneity, limited interpretability of complex models, a lack of large and diverse datasets, and insufficient clinical validation. The absence of standardized multi-omics data processing methods further restricts progress. This review systematically summarizes recent advances in AI-driven multi-omics research in AD, highlighting achievements in early diagnosis and biomarker discovery while discussing limitations and future directions needed to advance these approaches toward clinical application.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.