Therapeutic resistance in cancer is responsible for numerous cancer deaths in clinical practice. While target mutations are well recognized as the basis of genetic resistance to targeted therapy, nontarget mutation resistance (or nongenetic resistance) remains poorly characterized. Despite its complex and unintegrated mechanisms in the literature, nongenetic resistance is considered from our perspective to be a collective response of innate or acquired resistant subpopulations in heterogeneous tumors to therapy. These subpopulations, e.g., cancer stem-like cells, cancer cells with epithelial-to-mesenchymal transition, and drug-tolerant persisters, are protected by their resistance traits at cellular and molecular levels. This review summarizes recent advances in the research on resistant populations and their resistance traits. NOTCH signaling, as a central regulator of nongenetic resistance, is discussed with a special focus on its canonical maintenance of resistant cancer cells and noncanonical regulation of their resistance traits. This novel view of canonical and noncanonical NOTCH signaling pathways is translated into our proposal of reshaping therapeutic strategies targeting NOTCH signaling in resistant cancer cells. We hope that this review will lead researchers to study the canonical and noncanonical arms of NOTCH signaling as an integrated resistant mechanism, thus promoting the development of innovative therapeutic strategies.
Neoplasms/metabolism* ; Receptors, Notch/metabolism* ; Disease Resistance/physiology* ; Signal Transduction/physiology* ; Humans ; Drug Resistance, Neoplasm/physiology* ; Molecular Targeted Therapy/methods*

Irradiated blood emerged as a preventive measure for transfusion-associated graft-versus-host disease (TA-GVHD), ensuring the safety of blood transfusion for patients. In recent years, with the continuous development of transfusion medicine, the utilization rate of irradiated blood has been increasing, and there has been a growing number of studies on the effects of irradiation on blood components. Meanwhile, besides preventing TA-GVHD, irradiated blood holds promising applications in addressing other clinical transfusion issues. This article reviews the clinical applications and research of irradiated blood in transfusion medicine, aiming to provide a reference for achieving safe blood transfusion.

OBJECTIVES: We propose a sparse-view cone-beam CT reconstruction algorithm based on bidirectional flow field guided projection completion (BBC-Recon) to solve the ill-posed inverse problem in sparse-view cone-beam CT imaging. METHODS: The BBC-Recon method consists of two main modules: the projection completion module and the image restoration module. Based on flow field estimation, the projection completion module, through the designed bidirectional and multi-scale correlators, fully calculates the correlation information and redundant information among projections to precisely guide the generation of bidirectional flow fields and missing frames, thus achieving high-precision completion of missing projections and obtaining pseudo complete projections. The image restoration module reconstructs the obtained pseudo complete projections and then refines the image to remove the residual artifacts and further improve the image quality. RESULTS: The experimental results on the public datasets of Mayo Clinic and Guilin Medical University showed that in the case of a 4-fold sparse angle, compared with the suboptimal method, the BBC-Recon method increased the PSNR index by 1.80% and the SSIM index by 0.29%, and reduced the RMSE index by 4.12%; In the case of an 8-fold sparse angle, the BBC-Recon method increased the PSNR index by 1.43% and the SSIM index by 1.49%, and reduced the RMSE index by 0.77%. CONCLUSIONS The BBC-Recon algorithm fully exploits the correlation information between projections to allow effective removal of streak artifacts while preserving image structure information, and demonstrates significant advantages in maintaining inter-slice consistency.
Algorithms ; Cone-Beam Computed Tomography/methods* ; Image Processing, Computer-Assisted/methods* ; Humans

The gut microbiota is closely related to human health, and various gut microbiota health indices have been developed to assist in evaluating the health of the gut microbiota and even the overall health of the human body. Diets are one of the main factors that regulate the gut microbiota, while there is still no good method for evaluating the regulatory effects of dietary factors. To assess the regulatory effects of dietary factors on the gut microbiota of overweight individuals, we conducted an in vitro fermentation experiment based on 17 dietary factors, and developed an evaluation method for the regulatory effects of dietary factors based on the health index with principal component analysis (hiPCA). The results showed that most dietary factors had positive regulatory effects on the gut microbiota of overweight individuals. Galactooligosaccharides (GOS) and puerarin were the most significant dietary factors in regulating the gut microbiota of overweight individuals. The analysis of the contribution of species to the hiPCA indicated that GOS and puerarin might inhibit the activities of bacteria associated with overweight by regulating Eubacterium dolichum, Lactobacillus salivarius, Clostridium clostridioforme, Clostridium citroniae, and Lachnospiraceae bacterium 9_1_43BFAA. In addition, GOS may further enhance the inhibition of these activities by regulating Lachnospiraceae bacterium 6_1_63FAA, thereby reducing the gut health risks in overweight individuals. In summary, this study evaluated the health effects of dietary factors based on the hiPCA and specifically analyzed the role of different dietary factors in regulating the gut microbiota of overweight individuals. This provides new ideas and methods for improving gut microbiota health and has potential applications in the field of precision nutrition.
Humans ; Gastrointestinal Microbiome/physiology* ; Isoflavones/pharmacology* ; Overweight/microbiology* ; Diet ; Fermentation ; Oligosaccharides/pharmacology* ; Principal Component Analysis

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Objective To investigate the perioperative outcomes and postoperative pregnancy outcomes of patients with intrauterine adhesions(IUA)treated by see-and-treat hysteroscopy and traditional hysteroscopy in transcervical resection of adhesions(TCRA).Methods A retrospective cohort study was performed on 485 patients with moderate-to-severe IUA who met the inclusion criteria and admitted in our hospital from January 2019 to December 2021.According to surgical approaches,the patients were assigned into a see-and-treat mode group and a traditional mode group.After clinical diagnosis(ultrasound and symptoms)of IUA,the patients from the former group received direct hysteroscopic adhesion separation surgery,and those of the latter group were diagnosed by outpatient hysteroscopy first and then hysteroscopic adhesion separation surgery.The perioperative indicators,postoperative three-dimensional transvaginal ultrasound(3D-TVUS)examination related characteristics,postoperative menstrual recovery,postoperative pregnancy outcomes,obstetric related complications,and neonatal outcomes were collected and compared between the 2 groups.Results Among the enrolled 485 patients,there were 277 in the see-and-treat group and 208 in the traditional group.The success rate of surgical treatment was 89.89%in the see-and-treat group and 92.79%in the traditional group,but no statistical difference was seen between them(Chi-square=1.234,P=0.267).3D-TVUS examination displayed that the see-and-treat mode group obtained better improvement of endometrial morphology,uterine morphology and menstruation after operation than the traditional group(P<0.001).The postoperative pregnancy rate was slightly higher in the see-and-treat group than the traditional mode group(58.84%vs 58.17%,P=0.882).However,the see-and-treat mode showed obvious advantage in the postoperative natural pregnancy rate,with a rate of 90.80%,obviously higher than that in the traditional mode group(81.82%,P=0.026).The live birth rate was 70.55%in the see-and-treat mode group,excluding 1 case with ongoing pregnancy in the second trimester and 1 case with ongoing pregnancy in the third trimester,and the rate was 74.38%in the traditional group,excluding 3 cases with ongoing pregnancy in the third trimester,but there was no statistical difference between the 2 groups(P=0.303).In terms of obstetric-related complications,there were 0 cases of blood transfusion during delivery hospitalization in the see-and-treat group,while there were 7 cases in the traditional group(P=0.003).In neonatal outcomes,the rate of transfer to the pediatric department was 10.43%in the see-and-treat mode group and 22.22%in the traditional mode group(P=0.021).For health economics,the see-and-treat hysteroscopy group demonstrated a significant advantage over the traditional hysteroscopy group(P<0.001).There was no significant difference in pain scores between the 2 groups.Conclusion The see-and-treat approach is a safe,feasible,and highly efficient strategy for integrating the diagnosis and treatment of IUA,enabling maximal minimization of surgical trauma while optimizing time and cost efficiency.

Objective To explore the preventive effect of multidisciplinary collaborative evidence-based nursing on dysphagia in patients with orotracheal intubation in intensive care unit(ICU)after extubation.Methods A retrospective analysis was performed on 200 patients with orotracheal intubation in ICU who were admitted to Dongguan Traditional Chinese Medicine Hospital between January and December 2023.Of them,96 patients who were admitted to our hospital between January and May 2023 received routine nursing(routine group),104 patients who were admitted to our hospital between June and December 2023 received multidisciplinary collaborative evidence-based nursing(evidence-based group).The incidence of dysphagia after extubation,water swallowing test result,swallowing function measured with M.D.Anderson dysphagia inventory(MDADI),psychological state assessed by connor-davidson resilience scale(CD-RISC),quality of life assessed by swallowing quality-of-life questionnaire(SWAL-QOL),and the incidence of dysphagia complications(aspiration,aspiration pneumonia,and malnutrition)were compared between the two groups.Results The incidence of dysphagia after extubation and the water swallowing test class in the evidence-based group were lower than those in the routine group(both P<0.05).The total score of MDADI and CD-RISC scores in the evidence-based group were significantly higher than those in the routine group(P<0.05),while the SWAL-QOL scores were lower(P<0.05).The incidence of complications in the evidence-based group was significantly lower than that in the routine group(P<0.05).Conclusion Multidisciplinary collaborative evidence-based nursing can effectively reduce the incidence of dysphagia in patients with orotracheal intubation in ICU after extubation,improve swallowing function,psychological state and quality of life,and reduce the incidence of complications.

Objective To prepare recombinant human papillomavirus 58 L1 protein virus-like particles(HPV58 LI VLPs)in Pichia pastoris and immunize mice with the purified product to evaluate the immunogenicity of HPV58 L1 VLPs.Methods The HPV58 L1 multi-copy expression plasmid was constructed and transformed into Pichia pastoris KM71.The highly expressed Pichia pastoris engineering strain was screened and cultured in 5 L fermenter.The expressed HPV58 L1 VLPs were isolated and purified,which were then used to immunize 80 female BALB/c mice at different doses by intraperitoneal injection.After four weeks,the immune effect was evaluated by median effective dose(ED_(50)).Results Restriction analysis results showed that HPV58 L1 expression vectors were constructed correctly.Western blot,amino acid sequencing and transmission electron microscopy(TEM) results showed that HPV58 L1 protein was correctly expressed in Pichia pastoris and could self-assemble into VLPs at a diameter of about 50 nm.After purification by ion exchange and size exclusion chromatography,the HPV58 L1 VLPs reached a purity above 95%,and the ED_(50) in mouse model was 0.009 μg.Conclusion Recombinant HPV58 L1 VLPs with good immunogenicity were successfully prepared by using Pichia pastoris.

The Xuming Decoction, which is recorded in the "Gu Jin Lu Yan" section of Zhang Zhongjing's Synopsis of the Golden Chamber, is a traditional Chinese medicine formula. Recent literature review and summary of the clinical application research progress have found that this formula is primarily used to treat diseases such as acute cerebral infarction, facial neuritis, multiple sclerosis, Guillain-Barre syndrome, and pulmonary distension. However, different medical practitioners and scholars hold diverse understandings of Xuming Decoction.

Objective To assess the value of magnetic resonance imaging compilation(MAGiC)sequence in predicting lympho-vascular space invasion(LVSI)in early cervical cancer.Methods The data of 48 patients with cervical cancer confirmed by pathology were collected retrospectively,and classified into LVSI-positive group(n=29)and LVSI-negative group(n=19)according to postop-erative pathological results.MAGiC sequence images of patients were obtained before injecting contrast agents,then the region of interest(ROI)was delineated along the largest dimension edge of the lesion,and T1,T2 and proton density(PD)values were automatically generated by the software.Predictors were screened by univariate analysis and receiver operating characteristic(ROC)curves were drawn to assess their diagnostic efficacy for predicting LVSI in cervical cancer.Results Significant differences were found in T1 and PD values between LVSI-positive and LVSI-negative groups(P=0.003,P=0.017).There were no significant differences in T2 values between the two groups(P=0.414).The area under the curve(AUC)for T1 and PD values to predict LVSI status were 0.73 and 0.721,respectively.Conclusion LVSI-positive group of cervical cancer has lower T1 and PD values than LVSI-negative group based on MAGiC sequence.The MAGiC sequence has a certain application value for predicting LVSI status in early cervical cancer.