The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective To promote the objectification and intelligence of clinical TCM tongue diagnosis in ulcerative colitis(UC).Methods Daosheng DS01-B tongue and face diagnosis information collection system was used to prospectively collect tongue image pictures of patients with ulcerative colitis damp-heat in the large intestine syndrome(DCSR)and spleen deficiency dampness retention syndrome(PXSY),with totaling 1096 images.After UC tongue image segmentation,preprocessing,and data augmentation,a data set of UC tongue images was formed.Based on ResNet50,a UC tongue image classification model was constructed using feature fusion methods and attention modules.Results The UC tongue image classification model constructed had better classification performance,with an average F1 value of 85.09%,an AUC value of 0.83 for PXSY,and an AUC value of 0.81 for DCSR,both of which were higher than the VGG11 and ResNet50 models.Conclusion The constructed UC tongue image classification model can effectively identify DCSR and PXSY,providing a new approach to improve the accuracy and objectivity of UC differentiation and assisting in the intelligence of TCM tongue diagnosis.

[Objective]To study the academic characteristics of ZHANG's fever theory of Shanghai-style traditional Chinese medicine(TCM)of Sojae Semen Praeparatum herb pairs,and briefly analyze its clinical application in pulmonary epidemics.[Methods]Based on school-specific medical records,classical Chinese medical texts including Treatise on Cold Damage Diseases and Discussion of Warm Diseases,and modern pharmacological research,this study systematically summarizes the application features of Sojae Semen Praeparatum herb pairs in ZHANG's internal medicine for treating pulmonary epidemics.A representative case study was presented to exemplify ZHANG's clinical strategy of"pathogen elimination through dispersion".[Results]The ZHANG's internal medicine school has accumulated rich theories on and developed a profound and unique understanding of febrile diseases.By analyzing Sojae Semen Praeparatum's properties,efficacy and pairing principles,along with its commonly used herb combinations,an application system centered on"providing pathogens an exit route"was established.The proved case was of febrile disease in winter,and was treated with a modified decoction of Sojae Semen Praeparatum and achieved good results.[Conclusion]ZHANG's school employs Sojae Semen Praeparatum herb pairs with remarkable flexibility,addressing both pathological complexity and herbal synergism.The approach achieves significant therapeutic effects through pathogen dispersion,representing one of ZHANG's academic essences in treating pulmonary epidemics and providing valuable insights for modern TCM clinical practice.

Objective:To observe the effect of intravenous human immunoglobulin (pH4) (IVIg) on total immunoglobulin (Ig) levels in patients with B-cell non-Hodgkin lymphoma (NHL) and to evaluate its clinical efficacy in ameliorating hypogammaglobulinemia following CD20 monoclonal antibody therapy.Methods:Clinical data of 98 patients with B-cell NHL who developed hypogammaglobulinemia after CD20 monoclonal antibody therapy and were hospitalized in the Department of Hematology, The First Affiliated Hospital of Soochow University, from January 2018 to June 2022, were retrospectively analyzed. Patients were divided into the IVIg group ( n=70) and the conventional treatment group ( n=28). To exclude the interference of plasma transfusion on total Ig levels, statistical analysis was performed on the IVIg group without plasma transfusion ( n=53) and the conventional treatment group ( n=25). The therapeutic efficacy of IVIg was analyzed by observing its effect on elevating total Ig levels and the duration of this effect. The infection control efficacy of IVIg was assessed by comparing other blood biochemical parameters. The safety of IVIg in clinical application was also evaluated. Results:In the IVIg group, the mean total Ig level within 1-3 days after IVIg treatment was (20.67±4.17) g/L, significantly higher than the pre-treatment level of (17.16±1.76) g/L ( P<0.001). In 22 patients from the IVIg group, total Ig levels at 1-7 days, 8-14 days, and 15-30 days post-treatment were all significantly different compared to pre-treatment levels (all P<0.001). In the conventional treatment group, the mean total Ig level within 1-3 days after hospitalization showed no significant difference compared to the level at admission [ (18.12±1.84) g/L vs (18.43±1.79) g/L, P>0.05]. The proportion of patients in the IVIg group whose total Ig level reached 20 g/L within 1-3 days post-IVIg treatment was significantly higher than that in the conventional treatment group within 1-3 days after admission (57.69% vs 0, P<0.001). In 12 patients from the IVIg group with baseline neutrophil levels below normal, neutrophil levels at 1-3 days, 4-7 days, and 8-14 days post-treatment were significantly increased compared to pre-treatment levels (all P<0.05). The proportion of patients with new-onset infections post-treatment was lower in the IVIg group (22.64%, 12/53) than in the conventional treatment group (36.00%, 9/25), although the difference was not statistically significant ( P>0.05). Among 70 patients in the IVIg group, 8 patients experienced grade 1-2 adverse reactions, including nausea and vomiting in 5 patients, rash in 2 patients, and muscle/joint pain in 1 patient. No grade 3 or higher adverse reactions were observed. Conclusion:IVIg increased Ig and neutrophil levels in patients with B-cell NHL after CD20 monoclonal antibody therapy and may play a role in controlling new-onset infections. IVIg is effective and safe for treating hypogammaglobulinemia secondary to CD20 monoclonal antibody therapy in patients with B-cell NHL.

Objective:To investigate the diagnostic potential of serum Dickkopf-related protein 3(Dkk3)as a novel biomarker for sarcopenia in an elderly Chinese population by examining its correlation with muscle mass, muscle strength, and physical function.Methods:The study included elderly individuals aged ≥60 years from the Health Examination Center of Jiangsu Provincial Hospital between 2021 and 2022, who had independent mobility and were free from acute diseases.Fat and muscle mass were measured using Dual-energy X-ray Absorptiometry(DXA). Grip strength and chair stand test times were employed to assess upper and lower limb muscle strength, respectively.Physical function was evaluated using the Short Physical Performance Battery(SPPB). Serum Dkk3 concentration was measured using a human Dkk3 enzyme-linked immunosorbent assay(ELISA)kit.Results:A total of 108 elderly participants(83 males)were included in the study, with an age range of 60 to 97 years(mean age: 70.6±10.8). Serum Dkk3 concentration was found to be negatively correlated with the skeletal muscle mass index(SMI)( R=-0.292, P=0.002), lower limb muscle mass( R=-0.320, P<0.001), upper limb muscle mass( R=-0.222, P=0.020), and hip muscle mass( R=-0.261, P=0.006). Functional assessments revealed negative correlations with grip strength( R=-0.204, P=0.035), 4-meter walking speed( R=-0.195, P=0.043), the three-position balance test( R=-0.245, P=0.011), and the SPPB score( R=-0.196, P=0.043). Regression analysis indicated that, after adjusting for age, sex, body mass index(BMI), and comorbidities, Dkk3 remained negatively associated with lower limb muscle mass( β=-0.197, P=0.012), hip muscle mass( β=-0.156, P=0.029), and the SPPB score( β=-0.001, P=0.013). The sarcopenia group exhibited a 55.6% higher serum Dkk3 level compared to the control group(76.68±37.62 ng/ml vs.49.27±25.88 ng/ml, P<0.001). Receiver Operating Characteristic(ROC)curve analysis determined the optimal diagnostic threshold to be 80.08 ng/ml, with an area under the curve of 0.726, a sensitivity of 41.98%, and a specificity of 96.30% for detecting sarcopenia. Conclusions:Serum Dkk3 is closely associated with reduced muscle mass in the lower limbs and hips, as well as a decline in physical function, in elderly individuals with sarcopenia.Given its cost-effectiveness and clinical utility, serum Dkk3 shows potential as a meaningful biomarker for diagnosing sarcopenia in the elderly.

Objective:To investigate the clinical efficacy of posterior midline incision combined with anteromedial approach in the treatment of complex olecranon fracture-dislocation.Methods:A retrospective analysis was performed on 26 patients (15 males and 11 females) with olecranon fracture-dislocation who were admitted from January 2020 to January 2024, including 5 cases of anterior transolecranon fracture-dislocation (2 cases of upper ulnar-radial joint dislocation), 21 cases of posterior transolecranon fracture-dislocation (5 cases of them were accompanied by upper ulnar-radial joint dislocation). Among them, there were 13 cases of traffic accidents, 7 cases of falling from heights, and 6 cases of walking falls. The average age is 45.1±15.3 years old (21-84 years old).Results:The operation time was 151.2±41.9 minutes, average tourniquet time was 93.7±22.6 minutes, and the intraoperative blood loss was 76.2±20.2 ml. The average follow-up was 16(12, 23) months, and the VAS score decreased significantly and the MEPS score increased significantly over time. At the last follow-up, the VAS score was 2(1, 2), and the MEPS score was 86.5±10.3, with 16 cases excellent, 7 cases good, and 3 cases medium, with an excellent rate of 89%. The range of motion of flexion-extension and pronation-supination were 119.3°±13.5°and 138.6°±15.2° respectively. Complications included 16 cases of ectopic ossification, of which 4 patients with significant effects on elbow function underwent surgical release 3-6 months after surgery. 1 case of ulnar nerve injury symptoms improved after emergency ulnar nerve release, and 1 case of elbow subluxation due to inaccurate coronoid process reduction and fixation. There were no serious complications such as vascular injury, internal fixation failure, fracture nonunion, and incision infection.Conclusion:The posterior midline incision combined with anteromedial approach can effectively treat complex olecranon fracture-dislocation and meet the requirements of early postoperative elbow rehabilitation.

Objective:To evaluate preoperative high-resolution thin-layer cervical enhanced CT used to predict the venous route of the submental flap reflux vein and its relationship with adjacent structures in order to guide the anatomical understanding and protection of submental flap in pharyngeal cancer surgery.Methods:Sixty consecutive patients with pharyngeal cancer who underwent submental flap repair surgery in our department from March 2022 to December 2024, as well as 60 patients who were accepted neck dissection suffering other cancers, were selected. Before surgery, high-resolution cervical enhanced CT scans were performed, and the position of the transverse section of the facial vein in the venous phase horizontal image gradually variation tendency was focused layer by layer. The direction and adjacent relationship of the submental flap reflux veins were determined and recorded. Combined with 60 patients with other head and neck tumors who underwent neck dissection in our department during the same period (a total of 120 cases, 240 sides), the classification and management of the draining veins of Fang′s mental flap were conducted. Type Ⅰ mainly drains into the internal jugular vein; Type Ⅱ mainly drains into the external jugular vein and Type Ⅲ mainly drains into the anterior jugular vein (often accompanied by an external jugular draining branch). The status and proportion of venous drainage were analyzed.Results:Vascular predictive coincidence rate was 98.3% (59/60) among the 60 patients with pharyngeal cancer. Only one patient was predicted to have a simple return to the external jugular vein. However, during the operation, in addition to the main return to the external jugular vein, a small portion also returned to the internal jugular vein. Submental flap reflux vessels were classified into three types based on intraoperative submental flap venous return in 60 cases of laryngopharyngeal cancer, in conjunction with the analysis of venous return patterns from 240 cervical CT scans. Type Ⅰ mainly refluxed to the internal jugular vein, accounting for 42.1%. Type Ⅱ mainly refluxed to the external jugular vein (47.9%). Type Ⅲ mainly refluxed to the anterior jugular vein (10.0%). The total detection rate of CT reading of 240 venous reflux was 98.7% (237/240). Vascular predictive coincidence rate was 97.9%(235/240).Conclusion:The detailed analysis of submental venous return vessels can accurately predict the direction of reflux veins and its surrounding areas by preoperative high-resolution enhanced CT scan. This provides reliable guidance for the anatomy and protection of the submental flap reflux veins during surgery.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.