OBJECTIVE To investigate the ameliorative effect of ursolic acid on skin inflammation in rats with allergic contact dermatitis （ACD）， and explore its mechanism of action based on the Notch1/hairy and enhancer of split 1 （Hes1） signaling pathway. METHODS The ACD model was established by skin application of 2， 4-dinitrochlorobenzene. Forty successfully modeled rats were randomly divided into model control group （MC group）， ursolic acid low-dose group （UA-L group， 50 mg/kg）， ursolic acid high-dose group （UA-H group， 100 mg/kg）， and ursolic acid high-dose+Notch1 activator group （UA-H+Jagged1 group， 100 mg/kg ursolic acid+50 ng/kg Jagged1）， with 10 rats in each group. Another 10 rats with only hair shedding were selected as the normal control group. Rats in the administration groups were given the corresponding dose of ursolic acid intragastrically or/and Jagged1 by intraperitoneal injection once a day for 14 consecutive days. Twenty-four hours after the last treatment， the skin inflammation status and dermatitis scores of rats in each group were detected. The levels of interleukin-6 （IL-6）， IL-17 and IL-10 in serum and skin tissue were detected by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the pathological morphology of the skin tissue. Immunohistochemical staining and immunoblotting assay were used to detect the protein expressions of Notch1 and Hes1 in skin tissues. RESULTS Compared with the MC group， both the UA-L group and UA-H group exhibited significantly lower dermatitis scores， along with varying degrees of reduction in histopathological skin damage such as inflammatory cell infiltration. Additionally， the levels of IL-6 and IL-17 in serum and skin tissues were markedly decreased， while the levels of IL-10 were significantly increased in both groups； protein expressions of Notch1 and Hes1 were decreased significantly （P＜0.05）， and the improvements in the aforementioned indicators were more significant in the UA-H group （P＜0.05）. Jagged1 could significantly weaken the improvement effects of UA-H on the above indicators （P＜0.05）. CONCLUSIONS Ursolic acid may attenuate the expression of pro-inflammatory cytokines and enhance the expression of anti-inflammatory factors by blocking Notch1/Hes1 signaling pathway， thereby improving dermatitis symptoms in ACD rats.

[Objective] To assess the data characteristics of quality monitoring indicators for red blood cell (RBC) preparations, so as to provide reference for continuous improvement of blood quality. [Methods] The quality inspection data of 6 types of RBC preparations from Chongqing blood center from 2019 to 2023 were summarized. For the same indicators, the numerical range of quality indicators was monitored by comparing different types of preparations with the national standard GB18469. The loss and/or damage to RBCs caused by different preparation process were compared, and the impact of different preparation processes on the quality of RBCs was discussed. [Results] The appearance and sterility test compliance rates of the six types of RBC preparations were both 100%, while the compliance rates of other items were all ≥75%. The compliance rate of hematocrit for suspended RBCs was the lowest at 75%, with a median of 0.52, which was close to the lower limit of GB18469, while the medians of hematocrit for the other types were all at the midline level of GB18469. The Hb content for different types of RBCs was significantly higher than the corresponding requirements of GB18469 (P<0.05). The hemolysis rate at the end of storage for different types of RBCs was significantly lower than the requirements of GB18469 (P<0.05). The 1 U leukoreduction process resulted in a hemoglobin content loss of about 5% and had a significant impact on the hemolysis rate at the end of storage (P<0.05). The washing process resulted in a hemoglobin content loss of <3% and had no significant impact on the hemolysis rate at the end of storage (P>0.05). The concentration process resulted in a hemoglobin content loss of <3% and had a significant impact on the hemolysis rate at the end of storage (P<0.05). [Conclusion] The impact of different processes on RBC preparations is within a controllable range and meets the requirements of GB18469. The quality monitoring data can provide a reference for clinical blood selection, effectiveness evaluation and revision of related standards.

Organ damage from cancer treatment remarkably effects patients’ prognosis and quality of life. In recent years, preventive organ protection strategies, such as interdisciplinary collaboration, early prevention, precision interventions, psychological support, and the integrated application of traditional Chinese medicine, have demonstrated substantial clinical value and achieved notable progress. However, these approaches still encounter multiple challenges. Establishing multidisciplinary teams, optimizing therapeutic balance, and strengthening evidence-based research are essential for addressing the challenges related to treatment balance optimization, multidisciplinary coordination, and clinical translation of novel technologies. This review systematically summarizes recent advancements in preventive organ protection, analyzes existing challenges and potential solutions, and offers forward-looking recommendations. It aims to provide valuable insights for optimizing comprehensive cancer treatment strategies and improving long-term patient outcomes.

The life view of physique-qi-spirit trinity is the core theory for explaining the physiological activities of human body and the evolution of disease pathology in traditional Chinese medicine(TCM),and will bring about an overview of TCM tumorigenesis.This paper explores the biological basis of tumor from the perspective of disorders of physique,qi and spirit:there is a correlation between qi-physique transformation and energy and substance metabolism,and between spirit-emotion and neuromodulation;the nerve-metabolism pathway contributes to partial biological basis of tumor from the perspective of disorders of physique,qi and spirit.Furthermore,it puts forward the strategies for prevention and treatment with TCM through the simultaneous regulation of physique,qi and spirit:eliminating the mass to inhibit the tumor,and improving physique to preserve life in the view of treating physique;replenishing qi to strengthen the body,and ventilating qi to remove toxins in the view of treating qi;regulating the spirit to treat cancer through comprehensive therapy in the view of treating spirit.The exploration on the biological basis of tumor from the perspective of disorders of physique,qi and spirit will further embody the unique advantages of TCM theories in understanding malignant tumors,and will provide useful references for the model of synergistic prevention and treatment of malignant tumors with TCM.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

OBJECTIVE: To determine risk factors for cutout failure in geriatric intertrochanteric fracture patients after cephalomedullary nail fixation. METHODS: A retrospective review of 518 elderly patients who underwent cephalomedullary nail fixation for intertrochanteric fractures between January 2008 and August 2018 was conducted, including 167 males and 351 females, age from 65 to 97 years old. All patients were followed up for at least one year after surgery and divided into a healed group and a cutout group based on whether the hip screw cutout occurred. Among all patients, 10 cases experienced hip screw cutout. The general information, surgical data, and radiological data of the two groups were compared, and risk factors influencing hip screw cutout were analyzed. Propensity score matching was then performed on the cutout group based on gender, age, body mass index(BMI), and American Society of Anesthesiologists(ASA), and 40 patients from the healed group were matched at a ratio of 1∶4. Key risk factors affecting hip screw cutout were further analyzed. Multivariable logistic regression analysis was conducted to evaluate associations between variables and cutout failure. RESULTS: There were no statistically significant differences between the healed group and the cutout group in terms of age, gender, BMI, ASA, and AO classification. However, statistically significant differences were observed between the two groups in terms of reduction quality(P=0.003) and tip-apex distance(TAD), P<0.001. Multivariate analysis identified poor reduction quality OR=23.138, 95%CI(2.163, 247.551), P=0.009 and TAD≥25 mm OR=30.538, 95%CI(2.935, 317.770), P=0.004 as independent risk factors for cutout failure. CONCLUSION The present study identified poor reduction quality and TAD≥25 mm as factors for cutout failure in geriatric intertrochanteric fractures treated with cephalomedullary nails. Further studies are needed to calculate the optimal TAD for cephalomedullary nails.
Humans ; Male ; Female ; Hip Fractures/surgery* ; Aged, 80 and over ; Aged ; Risk Factors ; Retrospective Studies ; Fracture Fixation, Intramedullary/adverse effects* ; Bone Nails ; Bone Screws

PURPOSE: To comprehensively analyze the geographic and temporal trends of foot fracture, understand its health burden by age, sex, and sociodemographic index (SDI), and explore its leading causes from 1990 to 2019. METHODS: The datasets in the present study were generated from the Global Burden of Diseases Study 2019, which included foot fracture data from 1990 to 2019. We extracted estimates along with the 95% uncertainty interval (UI) for the incidence and years lived with disability (YLDs) of foot fracture by location, age, gender, and cause. The epidemiology and burden of foot fracture at the global, regional, and national level was exhibited. Next, we presented the age and sex patterns of foot fracture. The leading cause of foot fracture was another focus of this study from the viewpoint of age, sex, and location. Then, Pearson's correlations between age-standardized rate (ASR), SDI, and estimated annual percentage change were calculated. RESULTS: The age-standardized incidence rate was 138.68 (95% UI: 104.88 - 182.53) per 100,000 persons for both sexes, 174.24 (95% UI: 134.35 - 222.49) per 100,000 persons for males, and 102.19 (95% UI: 73.28 - 138.00) per 100,000 persons for females in 2019. The age-standardized YLDs rate was 5.91 (95% UI: 3.58 - 9.25) per 100,000 persons for both genders, 7.35 (95% UI: 4.45 - 11.50) per 100,000 persons for males, and 4.51 (95% UI: 2.75 - 7.03) per 100,000 persons for females in 2019. The global incidence and YLDs of foot fracture increased in number and decreased in ASR from 1990 to 2019. The global geographical distribution of foot fracture is uneven. The incidence rate for males peaked at the age group of 20 - 24 years, while that for females increased with advancing age. The incidence rate of older people was rising, as younger age incidence rate declined from 1990 to 2019. Falls, exposure to mechanical forces, and road traffic injuries were the 3 leading causes of foot fracture. Correlations were observed between ASR, estimated annual percentage change, and SDI. CONCLUSIONS The burden of foot fracture remains high globally, and it poses an enormous public health challenge, with population aging. It is necessary to allocate more resources to the high-risk populations. Targeted realistic intervention policies and strategies are warranted.
Humans ; Male ; Female ; Incidence ; Fractures, Bone/epidemiology* ; Middle Aged ; Adult ; Global Health ; Aged ; Global Burden of Disease ; Adolescent ; Child ; Young Adult ; Foot Injuries/epidemiology* ; Cost of Illness ; Child, Preschool ; Aged, 80 and over ; Infant

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

Lung cancer is the malignant tumor with the highest morbidity and mortality. The tumor-node-metastasis (TNM) staging has gradually shown its limitations in the accurate prediction of lung cancer, so it is urgent to construct a new clinical predictive model to guide the prevention and treatment of lung cancer. In recent years, as a comprehensive evaluation system based on peripheral immune related parameters, the value of peripheral immunoscore in the construction of predictive model has gradually become prominent. By quantifying the quantity and proportion of immune components in peripheral blood, the score can dynamically reflect the overall immune function and tumor microenvironment characteristics of the body. This paper systematically summarizes the latest research progress of peripheral immunoscore in early diagnosis, drug efficacy prediction, early warning of adverse reactions and prognosis evaluation of lung cancer, aiming to tap its potential clinical application value and provide some ideas and directions for developing new lung cancer-related predictive models.
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Humans ; Lung Neoplasms/drug therapy* ; Tumor Microenvironment ; Prognosis

Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.