ObjectiveTo observe the clinical efficacy and safety of Bushen Ruyan Formulation （补肾乳岩方， BRF） in treating premenopausal breast cancer patients of disharmony of the chong （冲） and ren （任） meridian type under endocrine intensive therapy. MethodsA total of 88 premenopausal breast cancer patients who received endocrine intensive therapy and were diagnosed with disharmony of the chong and ren meridian by traditional Chinese medicine （TCM） were included and randomly divided into a control group and a treatment group， with 44 cases in each group. The control group received ovarian function suppression （OFS） combined with endocrine therapy， while the treatment group was given oral BRF additionally. Both groups were treated for three months. The clinical efficacy was evaluated by comparing the pre- and post-treatment results of the Functional Assessment of Cancer Therapy-Breast （FACT-B）， modified Kupperman score， T cell subsets （CD3⁺， CD4⁺， CD8⁺， CD4⁺/CD8⁺）， sex hormone levels， including estradiol （E₂）， luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， progesterone （P）， testosterone （T）， and prolactin （PRL）， tumor markers， such as carcinoembryonic antigen （CEA）， carbohydrate antigen 125 （CA125）， and carbohydrate antigen 153 （CA153）， TCM syndrome score， and TCM syndrome efficacy. Blood routine tests， liver function and kidney function were monitored to assess safety. ResultsThe FACT-B scores of each domains and the total scores of the treatment group increased， while the social/family status score of the control group decreased. The treatment group had significantly higher scores in all domains and total score compared to the control group （P＜0.05 or P＜0.01）. The modified Kupperman score and TCM syndrome score of the treatment group decreased， and were lower than those of the control group （P＜0.01）. The levels of CD3⁺ and CD4⁺ in the treatment group increased， and were higher than those of the control group （P＜0.05）. Serum testosterone levels in the treatment group were lower than those in the control group （P＜0.05）. The total effective rate of TCM syndrome efficacy in the treatment group was 67.44%， significantly higher than the 23.26% in the control group （P＜0.05）. No significant abnormalities were observed in the blood routine tests or liver/kidney function indicators in either group before or after treatment. ConclusionBRF can effectively improve quality of life， alleviate symptoms， increase serum CD3⁺ and CD4⁺ levels， and enhance clinical efficacy in premenopausal breast cancer patients undergoing endocrine intensive endocrine therapy. It is also safe with no significant adverse effects.

Objective To investigate the effect of resveratrol on the tumor microenvironment in osteosarcoma. Methods A C57BL/6 xenograft mouse model was established and treated with resveratrol. Single-cell sequencing was performed to analyze changes in the tumor microenvironment. Immunohistochemistry was used to assess immune cell infiltration, while Western blotting was conducted to examine alterations in cellular signaling pathways. Results Resveratrol significantly inhibited the proliferation of LM8 osteosarcoma cells in C57BL/6 mice compared to the control group. Additionally, CD8⁺ T cell recruitment was enhanced. The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was notably downregulated in LM8 osteosarcoma cells following resveratrol treatment. Conclusion Resveratrol promotes CD8⁺ T cell infiltration by inhibiting the JAK2/STAT3 signaling pathway, suggesting its potential as a therapeutic agent in osteosarcoma treatment.
Osteosarcoma/genetics* ; STAT3 Transcription Factor/genetics* ; Resveratrol/pharmacology* ; Animals ; Janus Kinase 2/genetics* ; Signal Transduction/drug effects* ; Tumor Microenvironment/immunology* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice ; Humans ; Cell Proliferation/drug effects* ; Bone Neoplasms/metabolism* ; CD8-Positive T-Lymphocytes/drug effects* ; Xenograft Model Antitumor Assays

Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

BACKGROUND:Reactive oxygen species may be closely related to the occurrence and development of tendinopathy,but its exact role and related signal transduction mechanism have not been fully summarized. OBJECTIVE:To review current clinical or preclinical original studies,summarize the role of reactive oxygen species in tendinopathy and related signal transduction pathways and to explore its characteristics and whether there is a unified downstream pathway. METHODS:Relevant original studies in PubMed,Embase,Web of Science,as well as CNKI,WanFang,and VIP databases were searched by computer and the search results were screened and excluded according to the inclusion criteria.Ninety articles were finally included for review and analysis. RESULTS AND CONCLUSION:Reactive oxygen species affects the direction of tendon healing by simultaneously acting on tendon cells and the extracellular matrix,and it exhibits a bifacial effect in the treatment of tendinopathy.Concentration of reactive oxygen species may be the key to determining its direction of action.The possibility that low-dose reactive oxygen species can participate in the normal physiological healing of tendons or that tendon tissues are adaptive to stimulations may be the underlying mechanism that produces this characteristic effect.Reactive oxygen species affect the composition and structure of the extracellular matrix and normal tendon repair as well as maintain viability in response to external stimulations through matrix metalloproteinases,mitogen-activated protein kinases,mitochondrial apoptosis,the forkhead transcription factor O family,autophagy,inflammation,and antioxidant signaling pathways.Different reactive oxygen species stimulation intensities,durations,and external environments may cause different alterations in downstream molecular pathways and thus have different effects on the tendon.Due to the large gap in the number of literature included in the evaluation of the positive and negative effects of reactive oxygen species,it may cause some analytical error in the search for factors behind the characteristics of the action of reactive oxygen species in tendon.In addition,most experimental intervention conditions and results of interest are relatively homogeneous;therefore,the temporal and quantitative mechanisms of reactive oxygen species and the synergistic effects with other intervention factors have not been clarified,and the overall system of molecular actions of reactive oxygen species in tendinopathy has not been constructed.To conclude,reactive oxygen species might be involved in the treatment and prevention of tendinopathies as a beneficial factor in the future,and facilitate the exploration of oxidative stress signaling pathways and overall molecular action systems in tendinopathies thereafter,as well as lay the foundation for research on the therapeutic strategies of different antioxidants in tendinopathies to better prevent and treat tendon injury and degeneration.

Objective:To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL).Methods:A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children′s Hospital, Capital Medical University and Baoding Children′s Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients.Results:Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) ( χ2=1.88, 1.47, P=0.170, 0.224). Conclusions:Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Objective:To investigate predictive factors for successful endovascular recanalization in patients with non-acute symptomatic internal carotid artery occlusion (SICAO), to develop a decision tree model using the Classification and Regression Tree (CART) algorithm, and to evaluate the predictive performance of the model.Methods:Patients with non-acute SICAO received endovascular therapy at 8 comprehensive stroke centers in China were included retrospectively. They were randomly assigned to a training set and a validation set. In the training set, the least absolute shrinkage and selection operator (LASSO) algorithm was used to screen important variables, and a decision tree prediction model was constructed based on CART algorithm. The model was evaluated using the receiver operating characteristic (ROC) curve, Hosmer-Lemeshow goodness-of-fit test and confusion matrix in the validation set.Results:A total of 511 patients with non-acute SICAO were included. They were randomly divided into a training set ( n=357) and a validation set ( n=154) in a 7:3 ratio. The successful recanalization rates after endovascular therapy were 58.8% and 58.4%, respectively. There was no statistically significant difference ( χ2=0.007, P=0.936). A CART decision tree model consisting of 5 variables, 5 layers and 9 classification rules was constructed using the six non-zero-coefficient variables selected by LASSO regression. The predictive factors for successful recanalization included fewer occluded segments, proximal tapered stump, ASITN/SIR collateral grading of 1-2, ischemic stroke, and a recent event to endovascular therapy time of 1-30 d. ROC analysis showed that the area under curve of the decision tree model in the training set was 0.810 (95% confidence interval 0.764-0.857), and the optimal cut-off value for predicting successful recanalization was 0.71. The area under curve in the validation set was 0.763 (95% confidence interval 0.687-0.839). The accuracy was 70.1%, precision was 81.4%, sensitivity was 63.3%, and specificity was 79.7%. The Hosmer-Lemeshow test in both groups showed P>0.05. Conclusion:Based on the type of ischemic event, the time from the latest event to endovascular therapy, proximal stump morphology, the number of occluded segments, and the ASITN/SIR collateral grading constructed the decision tree model can effectively predict successful recanalization after non-acute SICAO endovascular therapy.

Objective To investigate the effect of acupuncture on fatigue improvement and gut microbiota in mice with cancer-related fatigue(CRF),and explore its possible mechanism of action.Methods The mice model of CRF of breast cancer after chemotherapy was established by tumor bearing and chemotherapy.After acupuncture intervention,fatigue was evaluated by general condition,forced swimming and open field experiment.Then 16S rDNA sequencing was used to analyze the structural abundance of gut microbiota in mice.Results Acupuncture could significantly improve the fatigue degree and general condition of the mice model of CRF of breast cancer after chemotherapy.At the same time,acupuncture could adjust the abundance of gut microbiota structure,up-regulate the abundance levels of Lactobacillus,Bacteroides,firmicutes,actinobacteria,and down-regulate the abundance levels of Proteobacteria and Staphylococcus.There were also differences in the abundance of flora structure among the groups,but the abundance of beneficial bacteria was relatively high in the acupuncture group,and the abundance of pathogenic bacteria was relatively high in the other two groups.Conclusion Acupuncture may play a role in the treatment of CRF by regulating the abundance of gut microbiota structure,increasing intestinal beneficial bacteria,inhibiting pathogenic bacteria,improving body immunity,and alleviating adverse reactions caused by chemotherapy for breast cancer.

Objective:To investigate the influencing factors, periprocedural complications, and long-term outcomes of successful recanalization after endovascular treatment in patients with non-acute symptomatic internal carotid artery occlusion.Methods:Patients with non-acute internal carotid artery occlusion received endovascular treatment in the Nanjing Stroke Registration System between January 2010 and December 2021 were retrospectively enrolled. Clinical endpoint events were defined as successful vascular recanalization, periprocedural complications (symptomatic embolism and symptomatic intracranial hemorrhage), neurological function improvement, and recurrence of ipsilateral ischemic events. Multivariate logistic regression analysis was used to investigate the independent influencing factors of successful vascular recanalization. Cox proportional hazards regression analysis was used to investigate the correlation between endovascular treatment outcomes and neurological function improvement, as well as ipsilateral ischemic cerebrovascular events. Results:A total of 296 patients were included, of which 190 (64.2%) were successfully recanalized. Multivariate logistic regression analysis showed that symptoms manifest as ischemic stroke (odds ratio [ OR] 3.353, 95% confidence interval [ CI] 1.399-8.038; P=0.007), the time from the most recent symptom onset to endovascular therapy within 1 to 30 d ( OR 2.327, 95% CI 1.271-4.261; P=0.006), proximal conical residual cavity ( OR 2.853, 95% CI 1.242-6.552; P=0.013) and focal occlusion (C1-C2: OR 3.255, 95% CI 1.296-8.027, P=0.012; C6/C7: OR 5.079, 95% CI 1.334-19.334; P=0.017) were the independent influencing factors for successful vascular recanalization. Successful recanalization did not increase the risk of symptomatic intracranial hemorrhage within 7 d after procedure (3.2% vs. 0.9%; P=0.428). The median follow-up time after procedure was 38 months. Cox proportional hazards regression analysis showed that after adjusting for confounding factors, successful recanalization was significantly associated with postprocedural neurological improvement (hazard ratio 1.608, 95% CI 1.091-2.371; P=0.017), and significantly reduced the risk of recurrence of long-term ischemic events (hazard ratio 0.351, 95% CI 0.162-0.773; P=0.010). Conclusion:In patients with non-acute internal carotid artery occlusion, successful endovascular recanalization can effectively reduce the risk of long-term ischemic events without increasing the risk of symptomatic intracranial hemorrhage.

Objective:To retrospectively analyze the gender differences in the clinical characteristics and perioperative outcomes of patients with type A aortic dissection in our institution.Methods:From January 2019 to January 2020, total 405 patients underwent surgical treatment for type A aortic dissection at Beijing Anzhen Hospital, including extensive aortic repair (total aortic arch replacement combined with stenting elephant trunk implantation) and limited aortic repair. In the entire cohort, male 295 cases, female 110 cases. All measures in this study were expressed as ± s or median(quartiles) and analyzed by Student t test for variables or non- parametric tests; count data were expressed as frequencies and percentages and analyzed by χ2 test and Fisher exact probability test. Independent risk factors were analyzed by logistic multivariate regression. Results:Females were older than males[(53.3 ± 12.4)years old vs. (47.1 ± 11.0)years old, P<0.001] and had significantly higher proportion of diabetes(9.1% vs. 4.1%, P=0.047) and previous cerebrovascular disease (11.8% vs. 5.8%, P=0.038). Females had a lower proportion of total aortic arch replacement combined with elephant trunk implantation (64.5% vs. 82.7%, P<0.001), while aortic cross-clamp time[168.0(144.8, 201.5) minutes vs. 190.0 (163.0, 217.0) minutes, P<0.001] and CPB time[99.0 (79.8, 118.0) min vs. 107.0 (91.0, 126.0) min, P=0.006] were significantly shorter than males. Females had significantly higher rates of pulmonary infection (14.5% vs. 5.8%, P=0.004) and stroke than males (15.5% vs. 8.1%, P=0.030). The difference in the proportion of postoperative deaths between female and male TAAD patients was not statistically significant (3.6% vs. 7.8%). Logistics multivariable regression analysis found that female was an independent risk factor for postoperative stroke ( OR=2.574, 95% CI: 1.198-5.531, P=0.015) and pulmonary infection ( OR=2.610, 95% CI: 1.180-5.772, P=0.018). Conclusion:Gender did not affect mortality after TAAD repair significantly, but females increased the risk of stroke and pulmonary infection after TAAD surgery.

Objective:To analyze the early risk warning factors of clinical characteristics in children with acute lymphoblastic leukemia (ALL) complicated with acute pancreatitis (AP).Methods:Retrospective study.A total of 39 children with ALL complicated with AP admitted to the Hematology Center of Beijing Children′s Hospital, Capi-tal Medical University from May 2018 to December 2020 were selected as the case group, and 78 ALL patients were randomly selected as the control group according to the exact matching of 1∶2 of the same age and sex.The measurment data and counting data were analyzed by Rank sum test ( Mann Whitney U test) and χ2 test between the 2 groups, respectively, and further multivariate Logistic regression analysis was performed to find out the risk factors of ALL complicated with pancreatitis.At the same time, the relationship between each index and severity was explored. Results:The incidence of ALL complicated with AP was 8.55% (39/456 cases). The high incidence age was 3-10 years old.Sixty-four point nine percent (24/37 cases) of the pancreatitis occurred in the early stage of chemotherapy, and 66.7% (26/39 cases) was associated with asparaginase.There were significant differences in ALL risk stratification ( χ2=21.404, P<0.001), C-reactive protein (CRP)( U=232.000, P<0.001), procalcitonin (PCT)( t=3.950, P<0.001), hematocrit( t=3.981, P<0.001), serum calcium( t=-9.609, P<0.001), indirect bilirubin( U=1 142.000, P<0.05), triglyceride( t=3.600, P=0.001) and albumin( t=-6.296, P<0.001) between the 2 groups.The sensitivity of abdominal CT, abdominal ultrasound and pancreatic magnetic resonance imaging in the case group were 70.8%, 81.6% and 100.0%, respectively.Multivariate Logistic regression analysis showed that differences between albumin( OR=11.444, 95% CI: 3.240-40.423), triglyceride( OR=18.047, 95% CI: 5.020-65.074) and risk stra-tification( OR=8.894, 95% CI: 1.889-41.885) were statistically significant, and there were obvious differences in PCT( U=3.000, 2.000, all P<0.05) and serum calcium( U=4.500, 8.500, all P<0.05) between patients with severe pancreatitis and patients with mild or moderate severe pancreatitis. Conclusions:ALL complicated with AP often occurs in the early stage of chemotherapy, mainly caused by asparaginase.In imaging examination, the sensitivity of pancreatic magnetic resonance imaging is the highest, followed by abdominal ultrasound.Risk stratification, decreased albumin and elevated triglyceride are risk factors of ALL complicated with AP, which are helpful for early identification of high-risk patients with ALL complicated with AP.PCT and serum calcium may play an important role in severe pancreatitis.