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.

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 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.

A Salmonella bacteriophage,PJN025,was isolated from wastewater and characterized for its biological properties,including whole-genome sequencing and assessment of therapeutic poten-tial in animal infection models.Transmission electron microscopy classified it within the Caudovi-ricetes family.PJN025 selectively lysed S.typhimurium and S.enteritidis with an incubation period of approximately 10 min,a burst time of 80 min,and an average burst size of approximately 132 PFU/cell,demonstrating effective bactericidal activity.The phage showed robust stability at temperatures ranging from 30 to 70 ℃ and pH levels from 3 to 12.Whole-genome sequencing re-vealed a complete genome length of 46 478 bp with a G+C content of 45.9％,consisting of 82 open reading frames and one tRNA.No known virulence or resistance genes were found.In Galleria mellonella infection model,a survival rate of 70％was achieved with a preventative dose of 1 × 108 PFU/mL PJN025,compared to a 5％survival rate in the positive control group after 48 h of bacterial challenge.In SPF mice infected with S.typhimurium via intraperitoneal injection,all mices in the positive control group died within five days.However,in the co-infection group treated with 1×108 PFU/mL PJN025,a promising survival rate of 60％was observed.This study showed that the bacteriophage PJN025 had strong specificity,high lytic efficiency,good acid and alkali tol-erance,strong heat resistance,and good safety and prevention effects,providing materials and ex-perimental basis for the development of subsequent phage products.

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.

This study aims to establish BHK-21 stable cell lines expressing APN from four species(human,pig,dog,and cat),the APN fragments were amplified from pEGFP-C1-APN plasmids of the four species stored in the laboratory to generate the recombinant plasmids pcDNA4.0-APN.Af-ter the recombinant plasmids were transfected into BHK-21 cells,the stable BHK-21 cell lines ex-pressing the APNs were selected by two rounds of limited dilution.The constructed BHK-21 cell lines were identified by indirect immunofluorescence assay(IFA),and their susceptibility to PD-CoV and TGEV was tested for these four cell lines.Virus infection experiments revealed that PD-CoV infected cells expressing human,pig,and dog APNs,while it did not infect cells expressing cat APN.Simultaneously,TGEV infected cells expressing pig,dog,and cat APNs,but did not infect cells expressing human APN.The results suggest that the risk of cross-species infection for different coronaviruses and the established cell line can be used effectively to evaluate the virus in-fection.The findings also revealed that PDCoV has the potential risk of cross-species infection of human and dog,and TGEV has the potential risk of cross-species infection of dog and cat.These results provide a basis for the prevention and control strategy of coronaviruses.

This study was aimed at investigating the effectiveness of various host nucleic acid removal and non-specific amplifica-tion techniques in animal tissue samples,to increase the accuracy of pathogen identification in tissue samples.Simulated samples were prepared with a mixture of mouse lung tissue homogenates and Klebsiella pneumoniae fluids,and processed with six host nucleic acid removal kits and three non-specific amplification techniques.The effectiveness of each method in removing host DNA and enriching nucleic acids of pathogenic microorganisms was evaluated through real-time fluorescence quantitative PCR and high-throughput se-quencing.For host nucleic acid removal techniques,the method of selective cleavage and quantitative degradation of host DNA(Com-plete5 kit)effectively decreased the host nucleic acid content in tissue samples and increased the relative abundance of pathogen nucleic acids.In contrast,the magnetic bead method for host DNA removal(Next microbiome DNA enrichment Kit kit)was less effec-tive.At lower pathogen concentrations(77 CFU/mL),the Vazyme kit was more effective than the other kits in removing host nucleic acids.Non-specific amplification techniques(MALBAC whole genome amplification,MDA isothermal amplification,and random primer amplification)were not applicable to tissue samples and were not effective in increasing the relative abundance of pathogen nucleic acids.Selective lysis and quantitative degradation of host DNA were suitable for processing tissue samples with high host back-ground and low pathogenic microorganism levels,whereas non-specific amplification methods were not applicable to tissue samples for pre-processing of macro-genome high-throughput sequencing.

Drug addiction,also referred to as drug dependence or substance use disorder,is a chronic and recurrent brain disease.Its main characteristics are compulsive drug-seeking behavior,continued use of drugs,and a loss of control over intake.Prolonged use of addictive substances can result in both physiological and psychological dependence.When usage is ceased,individuals may experience intense discomfort,including anxiety,insomnia,nausea,vomiting,and a strong craving for the substances.Drug dependence is classified into two types:physical dependence and psychological dependence.Physical dependence describes a pathological state of adaptation that results from the repeated use of addictive substances,leading to severe withdrawal syndrome upon cessation.Psychological dependence involves a mental craving for addictive substances,which is needed to experience the specific euphoria that follows consumption.Regular or continuous use is required to sustain these euphoric effects.The mechanisms of addiction are complex and influenced by genetic,environmental,and various other factors.They involve higher-level neurological activities,such as memory,reward,and decision-making.Currently,effective treatment methods for drug addiction are insufficient.Due to the complexity of drug addiction,laboratory animal research is essential.Using animal behavioral models to simulate human drug addiction can enhance our understanding of the mechanisms of addiction.This research offers a comprehensive overview of various animal experimental models that explore both physical and psychological dependence.It includes detailed descriptions of the methods and procedures used to assess physical dependence,behavioral sensitization,conditioned place preference,drug discrimination,and self-administration experiments.Additionally,the characteristics of each experimental model are compared,and the relevance of these models is discussed,aiming to provide support for the research on addiction mechanisms and the development of therapeutic methods.

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 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.