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 explore the occult clinical features and diagnostic difficulties of transfusion-related anaphylactic shock (TRAS) in patients with severe burns through a retrospective case analysis, and to provide practical references for improving the early identification and treatment efficiency of such atypical allergic reactions. Methods: The clinical data of a patient with severe burns (60%TBSA) who developed severe anaphylactic shock after intraoperative plasma transfusion were retrospectively analyzed. Transfusion reaction laboratory investigations, including blood group re-verification, unexpected antibody screening, and the Coombs test, were performed to rule out hemolytic transfusion reactions and blood group incompatibility. Together with the patient's lack of typical cutaneous allergic signs, ineffective response to conventional vasopressor therapy, and the rapid reversal of the condition following anti-allergic treatment (epinephrine plus glucocorticoids), the diagnosis was established and the recognition pathway was summarized. Results: Immediately after plasma transfusion, the patient developed severe hypotension (50/40 mmHg) accompanied by altered mental status, tachycardia, and shock manifestations. Because of the extensive burn wounds over the whole body, typical allergic signs such as urticaria and skin flushing were not observed. Blood pressure could not be maintained after rapid fluid resuscitation and conventional vasopressor therapy, but recovered rapidly after switching to epinephrine combined with glucocorticoid pulse therapy, and vital signs tended to be stable. Prophylactic anti-allergic drugs were administered before subsequent transfusions, and no similar adverse reactions occurred. Conclusion: Transfusion-related allergic reactions in patients with severe burns are characterized by occult clinical manifestations, with skin signs often masked by burn wounds, which can easily lead to diagnostic delay. Reverse verification through the rapid response to anti-allergic therapy after failure of conventional anti-shock treatment is a key clinical approach for identifying atypical anaphylactic shock. It is recommended to establish an early warning mechanism focusing on hemodynamic monitoring within 15 minutes after transfusion, and develop individualized transfusion protocols, including preoperative allergic history assessment and prophylactic anti-allergic medication, for patients with severe burns, so as to enhance transfusion safety in this high-risk population.

Hepatocellular carcinoma(HCC),as the most common type of liver cancer,poses a significant threat to global public health due to its high incidence and mortality rates.This paper delves into the etiology,pathogenesis,and syndrome differentiation of liver cancer from the perspective of"dispersing qi and fortifying the body resistance",based on the clinical experience of renowned traditional Chinese medicine(TCM)practitioner,Prof.Changquan Ling.Prof.Ling believes that the development of liver cancer is closely related to the disruption of liver qi flow,the accumulation of blood stasis over time,and the generation of toxin from long-term stagnation,accompanied by pathological changes such as imbalance of yin and yang,deficiency of the body's vital qi and accumulation of pathogenic factors,and internal blazing of cancer toxins.In terms of treatment,he emphasizes the principles of dispersing qi and fortifying the body resistance,addressing both the root cause and symptoms.This is achieved by regulating the functions of viscera,improving the stagnation of qi flow,and supplemented by methods such as clearing heat and detoxifying,and softening and dispersing hard masses,aiming to break the vicious cycle of qi stagnation,deficiency of vital qi,and pathogenic factor generation,thereby promoting the recovery from the disease.Through detailed analysis of clinical cases,this paper demonstrates Prof.Ling's unique insights and significant efficacy in treating liver cancer through"dispersing qi"to"fortify the body resistance",ultimately achieving"tumor suppression".This provides new references and perspectives for the clinical diagnosis and treatment of liver cancer in TCM.

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

Hepatocellular carcinoma(HCC),as the most common type of liver cancer,poses a significant threat to global public health due to its high incidence and mortality rates.This paper delves into the etiology,pathogenesis,and syndrome differentiation of liver cancer from the perspective of"dispersing qi and fortifying the body resistance",based on the clinical experience of renowned traditional Chinese medicine(TCM)practitioner,Prof.Changquan Ling.Prof.Ling believes that the development of liver cancer is closely related to the disruption of liver qi flow,the accumulation of blood stasis over time,and the generation of toxin from long-term stagnation,accompanied by pathological changes such as imbalance of yin and yang,deficiency of the body's vital qi and accumulation of pathogenic factors,and internal blazing of cancer toxins.In terms of treatment,he emphasizes the principles of dispersing qi and fortifying the body resistance,addressing both the root cause and symptoms.This is achieved by regulating the functions of viscera,improving the stagnation of qi flow,and supplemented by methods such as clearing heat and detoxifying,and softening and dispersing hard masses,aiming to break the vicious cycle of qi stagnation,deficiency of vital qi,and pathogenic factor generation,thereby promoting the recovery from the disease.Through detailed analysis of clinical cases,this paper demonstrates Prof.Ling's unique insights and significant efficacy in treating liver cancer through"dispersing qi"to"fortify the body resistance",ultimately achieving"tumor suppression".This provides new references and perspectives for the clinical diagnosis and treatment of liver cancer in TCM.

Objective To evaluate the impact of different exercise frequencies on the symptoms,quality of life,and duration of rehabilitative effects in patients with Parkinson's disease(PD).Methods A total of 90 PD patients(Hoehn and Yahr stage ≤3,receiving continuous dopaminer-gic stimulation)admitted in Department of Neurology of Chinese PLA General Hospital were en-rolled and randomly divided into groups G1,G2 and G3,with 30 participants in each group.They received rehabilitation exercises of Parkinson's Wellness Recovery(PWR)1 h per time,at differ-ent frequencies,that is,once(G1),twice(G2)and three times(G3)a week,for totally 6 months.Unified Parkinson's disease rating scale(UPDRS),levodopa equivalent dose,10-meter walk test(10-MWT),Fullerton advanced balance(FAB)Scale,trail making test-A(TMT-A),nine-hole peg test(9-HPT)and Parkinson's disease questionare-39(PDQ-39)were applied to evaluate the efficacy of the rehabilitation.Results The PDQ-39 score was significantly decreased in all the three groups after PWR exercise(P＜0.05,P＜0.01).Compared with the corresponding levels before intervention,the group G2 had obviously lower 10-MWT score and higher FAB score(P＜0.05),and the group G3 obtained notably decreased scores in UPDRS,UPDRS-Ⅲ,10-MWT,TMT-A,9-HPT,and PDQ-39[30.72±11.31 vs 31.41±10.42,P=0.001;19.21±9.72 vs 20.17±8.80,P=0.001;7.38(6.26,8.49)s vs 7.48(6.53,8.56)s,P=0.004;53.97±8.74 s vs 54.07±8.62 s,P=0.026;38.71(33.71,49.71)s vs 38.90(33.78,49.82)s,P=0.001;28.00(14.50,36.00)vs 30.00(15.50,38.50),P=0.001],and increased FAB score[23.00(16.00,33.00)vs 21.00(16.00,32.00),P=0.005].In addition,the patients in the G3 group experienced the most pronounced re-habilitation effect immediately after exercise,but,all aforementioned indicators remained augmen-ted even 4 weeks after exercise.Conclusion Exercise rehabilitation three times weekly can greatly enhance the motor function of PD patients,ameliorate non-motor symptoms,and the overall quali-ty of life,with the beneficial effects persisting for a minimum of 4 weeks.

Objective:To investigate the potential characteristic manifestations and application value of the Dynamic Visual Acuity Test（DVAT） in vestibular migraine（VM）. Methods:A total of 50 VM patients（case group） and 50 healthy subjects（control group） diagnosed at the Department of Otorhinolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University between November 1, 2023, and December 31, 2024, were enrolled. The case group underwent DVAT, video head impulse test（vHIT）, caloric test, and Dizziness Handicap Inventory（DHI） assessment, whereas the control group only received DVAT. Group-based analyses were conducted to examine the effect of age on Dynamic Visual Acuity Loss（DVALoss）, as well as the correlations of DVALoss with vestibular function tests and DHI scores. Results:DVALoss in the case group was significantly higher than that in the control group（P<0.001）. In both groups, age was significantly and positively correlated with DVALoss（P<0.001）. Within the case group, DVALoss was strongly and positively correlated with DHI scores（r=0.807, P<0.001）; it was negatively correlated with the vestibulo-ocular reflex（VOR） gain in vHIT, though without clinical significance, and showed no significant association with the caloric test. Age and DVALoss collectively accounted for 71.3% of the variance in DHI scores（R²=0.713）, with age exerting a relatively minor actual impact. Conclusion:DVAT can sensitively identify the core functional impairments of VM. DVALoss, as a direct functional reflection of the pathological mechanism of VM, is strongly correlated with DHI scores. Incorporating DVALoss into standardized assessments may provide an objective basis for the diagnosis and management of VM.
Humans ; Migraine Disorders/diagnosis* ; Visual Acuity ; Case-Control Studies ; Head Impulse Test ; Vestibular Function Tests ; Female ; Male ; Adult ; Vestibular Diseases/physiopathology* ; Middle Aged ; Caloric Tests

N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

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*