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*

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 introduce the application scene,operating steps and preliminary clinical effect of tibial bone mass preservation technique in medial unicompartmental knee arthroplasty(MUKA).Methods A total of 15 patients with antero-medial knee osteoarthritis(AMOA)treated in this hospital from May 2022 to May 2023 were selected as the study subjects.The tibial bone mass preservation technique was a-dopted to complete MUKA(fixed platform prosthesis).The operating time,intraoperative bleeding volume,hospitalization duration and operation complications were recorded.The VAS score before operation and in last follow up,range of motion(ROM)of knee joint,Knee Society Score(KSS),hip and knee stomping angle(HKA)of lower extremity in the operation side and image results were recorded to evaluate the clinical effect.Results The operations in 15 cases were successfully completed.The average operation time was(82.73±9.97)min,mean intraoperative bleeding volume was(21.00±9.49)mL and average hospital stay was(4.9±1.4)d.There was no intraoperative nerve,vascular and medial collateral ligament injury,no iatro-genic fracture,and no postoperative surgical site infection.All patients were followed up for average(5.87±2.77)months.The VAS score of knee joint,ROM,KSS and HKA angle of lower limb in the operated side were significantly improved compared with before operation(P<0.05).There was no prosthesis loosening,displacement or fragmentation,and no obvious degeneration aggravation of the lateral compartment of the knee joint.Conclusion The tibial bone mass preservation technique is a simple,effective and reliable method to deal with the slightly tight flexion space after tibial osteotomy during MUKA,and the postoperative clinical efficacy and imaging results are excellent.

OBJECTIVE To investigate the relationship between the expression level of endotoxin and soluble interleukin-2 receptor(sIL-2R)and the occurrence of suppurative otitis media in patients with nasopharyngeal carcinoma after radiotherapy.METHODS Seventy-nine nasopharyngeal cancer patients who received radiotherapy in Nanyang Downtown Hospital between January 2022 and July 2023 were selected as the study subjects,and they were followed up for a period of 1 year,and then grouped according to the occurrence of suppurative otitis media during the follow-up period,i.e.,21 cases in the occurringgroup and 58 cases in the non-occurring group,and the baseline data of patients in the two groups were compared,and the levels of endotoxin and sIL-2R were detected at the end of radiotherapy and analyze the relationship between endotoxin,sIL-2R and the occurrence of purulent otitis media after radiotherapy for nasopharyngeal carcinoma.RESULTS A total of 21 cases(26.58%)of 79 nasopharyngeal carcinoma patients developed suppurative otitis media after radiotherapy.Compared with the non-occurrence group,the radiotherapy time,endotoxin,sIL-2R,TNM stage Ⅲ,Eustachian tube involvement,nasal cavity structural abnormality,inflammatory reaction,and palatal sail tensor atrophy degree≥30%were high in the occurrence group,and the difference was statistically significant(all P<0.05).The results of logistic multifactorial analysis showed that inflammatory reaction,endotoxin,abnormal nasal structure,TNM stage(Ⅲ),sIL-2R,Eustachian tube involvement,duration of radiotherapy,and degree of atrophy of palatofacial tensor atrophy≥30%were all risk factors for suppurative otitis media.The results of Spearman's rank correlation analysis showed that endotoxin and sIL-2R were positively correlated with the occurrence of septic otitis media(r=0.493,0.516,P<0.001).Analysis using the ROC curve showed that:endotoxin:AUC value:0.657,sensitivity:61.90%,specificity:72.41%,accuracy:69.62%,95%CI=0.523-0.791;sIL-2R:AUC value:0.697,sensitivity:71.43%,specificity:67.24%,accuracy:68.35%,95%CI=0.566-0.829;combined test:AUC value:0.804,sensitivity:95.24%,specificity:65.52%,accuracy:73.42%,95%CI=0.705-0.903,the best value of the two combined tests.CONCLUSION The elevated levels of endotoxin and sIL-2R in patients with nasopharyngeal carcinoma after radiotherapy may be associated with suppurative otitis media.

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 analyze the correlation between the pulmonary immune prognostic index(LIPI)and the prognosis of patients with advanced non-small cell lung cancer(NSCLC)treated with sintilimab.Methods A total of 145 patients with advanced NSCLC were selected as study subjects.All patients received treatment with sintilimab,and their clinical baseline data were recorded.Accord-ing to the LIPI score,patients were divided into low-risk,intermediate-risk,and high-risk groups.The correlation between LIPI and the prognosis of advanced NSCLC patients was analyzed.Factors in-fluencing progression-free survival(PFS)and overall survival(OS)were identified.Results Univa-riate analysis showed that patient age,smoking status,pathological type,clinical stage and LIPI were factors affecting PFS(P＜0.05);age,pathological type,clinical stage and LIPI were factors affecting OS(P＜0.05).Multivariate Logistic regression analysis revealed that age of 60 to 70 years,age＞70 years,adenocarcinoma,stage Ⅳ and high-risk LIPI were independent prognostic factors of PFS(P＜0.05);age＞70 years,poor stage Ⅳ,adenocarcinoma and high-risk LIPI were independent prognos-tic factors of OS(P＜0.05).LIPI influenced patient's prognosis,with low-risk patients showing better outcomes and longer median PFS and OS.Conclusion LIPI is correlated with the prognosis of advanced NSCLC patients treated with sintilimab.Patients with a low-risk LIPI assessment benefit more from sintilimab treatment.

ObjectiveTo investigate the impact of acute respiratory infections in children under 12 years old in Pudong New Area， Shanghai from 2019 to 2023. MethodsAcute respiratory infection samples of children under 12 years old from three sentinel hospitals in Pudong New Area， Shanghai from 2019 to 2023 were collected， and 42 respiratory infection pathogens， including influenza virus， adenovirus， parainfluenza virus， respiratory syncytial virus， human enterovirus/rhinovirus， human pulmonary virus， human bokavirus， coronavirus （229E， HKU1， NL63 and OC43）， and novel coronavirus， were detected with microfluidic chips. The situation of acute respiratory infections among outpatient and inpatient children in this area was analyzed for the before the implementation of non pharmacological intervention measures （2019.12‒2020.1）， during the period of non pharmacological intervention measures （2020.2‒2022.12）， and after non pharmacological intervention measures （2023.1‒2023.6）. ResultsFrom 2019 to 2023， a total of 1 770 samples were collected， and 445 pathogens were detected， with a detection rate of 25.14% （445/1 770）. The main pathogens detected during the study period were influenza virus： 8.70% （154/1 770）， respiratory syncytial virus： 4.41% （78/1 770）， human enterovirus/rhinovirus： 2.66% （47/1 770）， human adenovirus： 2.49% （44/1 770）， and parainfluenza virus： 2.20% （39/1 770）. Before the implementation of non pharmacological intervention measures， outpatients were primarily infected with influenza， parainfluenza virus， and respiratory syncytial virus， with detection rates of 8.09%， 4.49%， and 4.04%， respectively； inpatients were mainly infected with influenza， respiratory syncytial virus， and parainfluenza virus， with detection rates of 4.49%， 3.82%， and 3.15%， respectively. During the period of non pharmacological intervention measures， influenza， rhinovirus and respiratory syncytial virus were the main viruses detected in the samples of outpatient children， with detection rates of 4.04%， 3.60%， and 2.47%， respectively； inpatient samples mainly detected respiratory syncytial virus， rhinovirus， and influenza virus， with detection rates of 3.60%， 2.02%， and 1.80%， respectively. After non pharmacological intervention measures， influenza， rhinovirus and respiratory syncytial virus were the main pathogens detected in the outpatients， with detection rates of 9.89%， 2.92% and 2.02%， respectively； influenza， respiratory syncytial virus， and rhinovirus were the main pathogens detected in inpatient children， with detection rates of 6.29%， 1.57%， and 1.35%， respectively. ConclusionThe prevalence of pathogens related to acute respiratory infections in children is influenced by non pharmacological preventive measures.

Background In recent years, radiation diagnosis and treatment technology has been increasingly applied and popularized in the medical field, and the status of radiation health protection has attracted widespread attention. Objective To understand the knowledge, attitude, and behavior of radiological health protection in radiation workers in Jiading District of Shanghai. Methods Convenience sampling method was used to select 441 radiation workers from 33 medical institutions in Jiading District, Shanghai to conduct a questionnaire survey from May to August 2023. Basic information and radiation protection associated knowledge, attitude, and behavior were collected from the study participants, and the scores of knowledge, attitude, and behavior were calculated. Factors affecting the behavior were evaluated by multiple linear regression. Results A total of 441 subjects were included in this study, with an age range of 22-71 years, 53.06% male and 46.94% female. In terms of knowledge, the correct response rate of the study subjects to the seven questions on the basics of radiation protection ranged from 44.22%-96.60%, with the lowest rate of 44.22% for the question on "radiation stochastic effect diseases". The subjects acquired knowledge about radiation hygiene mainly through vocational training (98.41%), and wanted to acquire knowledge mainly about the basics of nuclear and radiation (76.42%). In terms of attitude, the recognition level (strongly agree/agree) of the study subjects on the six attitude questions ranged from 73.47% to 96.37%, in which only 56.92% of the radiological staff at tertiary hospitals believed that the radiation dose they were exposed to at work would be hazardous to their health, and 73.85% believed that it was necessary to participate in training on knowledge of radiological protection, both lower than those in other levels of hospitals. In terms of behavior, the implementation rate (always/often) of the five behavioral questions by the study participants ranged from 75.28% to 91.84%, and there was a statistically significant difference in the total behavioral scores of the study participants by levels of hospitals (P=0.015). The results of multiple linear regression showed that gender, age, and radiation work permit associated with the behavioral scores of the study subjects. Conclusion In Jiading District, Shanghai, the coginitive rate of radiation workers' basic knowledge of theoretical protection still needs to be improved, and occupational training should be carried out in a targeted manner; the attitude of radiation workers varies by levels of hospitals, and the publicity and education of workers at tertiary hospitals in particular should be strengthened; and the supervision and management of male, senior, and non-certified radiation workers in hospitals of different levels should be enhanced.

ObjectiveTo design a prospective nested case-control study based on a city-wide birth cohort of Shanghai， so as to understand their health status and explore the influencing factors of birth defects. MethodsBased on the birth registration covering the entire city of Shanghai， the nested case-control study of children with severe birth defects was designed. Children born with severe birth defects were selected as the case group， and healthy children were matched as the control group. Basic information， health status， maternal pregnancy history， and survival outcome of children both in the case group and the control group were collected through medical history review and home visits. The logistic regression model was used for multivariate analysis. ResultsA total of 18 875 infants born between January 1， 2011， and December 31， 2021， were included， among which 11 500 （60.93%） were children with severe birth defects and 7 375 （39.07%） were healthy children. The logistic regression model analysis showed that being male （OR=1.20， 95%CI：1.13‒1.29）， non-Shanghai residency （OR=1.16， 95%CI： 1.06‒1.25）， multiple births （OR=8.41， 95%CI：6.25‒11.30）， artificial insemination （OR=2.31， 95%CI：1.34‒3.99）， in vitro fertilization （IVF） （OR=1.85， 95%CI：1.44‒2.38）， maternal exposure to radiation （OR=1.83， 95%CI：1.07‒3.14）， maternal illness during pregnancy （OR=1.61， 95%CI：1.49‒1.74）， experiencing a traumatic event during pregnancy （OR=2.34， 95%CI：1.88‒2.92）， paternal chemical exposure （OR=1.88， 95%CI：1.32‒2.69）， paternal radiation exposure （OR=1.65， 95%CI： 1.18‒2.33）， family history of birth defects （OR=8.18， 95%CI： 3.96‒16.89）， being overweight before pregnancy （OR=1.16， 95%CI： 1.07‒1.27）， being obese before pregnancy （OR=1.15， 95%CI：1.03‒1.30）， and being excessively obese before pregnancy （OR=1.52， 95%CI：1.26‒1.83） were risk factors for the occurrence of birth defects. Analysis by type of birth defect found that prematurity was a risk factor for cardiac malformations and cheilopalatoschisis （OR=27.87， 95%CI： 20.84‒37.27）， especially ranking first in cardiac malformations. ConclusionAfter controlling for influencing factors， maternal overweight， obesity， and excessive obesity before pregnancy， artificial insemination， and IVF are independent risk factors for the occurrence of birth defects. Choosing a healthy lifestyle， improving physical and mental health during pregnancy， and controlling BMI during pregnancy are beneficial in reducing the risk of birth defects.

Background::Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully understood.Methods::We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells. In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin. Results::Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin sensitivity.Conclusion::In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.