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.

Objective To evaluate the application of modified chairside case-based learning(CBL)in the teaching of dental residents in the prosthodontic clinic.Methods Dental residents in Peking Union Medical College Hospital from September 2022 to September 2024 were enrolled.Traditional CBL was conducted in control group.Modified chairside CBL was conducted in test group.The scores of department rotation examination and questionnaire results were analyzed with t-test statistical analysis.Results The score of"patient reception"in test group was significantly higher than control group(P＜0.05).24 valid questionnaires were collected in two groups each.The rate of approval in test group was significantly higher than control group in the following items of questionnaire,including"reduce learning pressure or burden""improve the capacity of doctor-patient communication""improve the capacity of literature review""improve the capacity of group cooperation"(P＜0.05).Conclusions Modified chairside CBL has showed good teaching effects in improving the capacity of patient reception,doctor-patient communication,literature review,group cooperation,and meanwhile reduced learning pressure or burden.

Objective To explore the need and evaluate the effectiveness for head-simulator in the teaching of sto-matology within the eight-year program of clinical medicine.Methods Questionnaire survey was conducted among the students from 2017 cohort of the eight-year program of clinical medicine at Peking Union Medical College.The survey results were statistically analyzed and described.Results Totally 87.9％of the students believed that incor-porating head-simulator into the clinical practice course of stomatology were necessary,and 93.9％expressed will-ingness to join the training.Most students preferred to practice peri-odontal scaling and cavity preparation for caries during the simulated training sessions.The majority of students considered two or four class hours of simulated head teaching to be reasonable.The pilot head simulation training was successfully implemented;75.0％of the students acknowledged clear teaching and convincible demonstrations.All the trainees agreed that the head simulation course helped them better understand stomatology knowledge,stimulated their interest in learning and expressed a desire for increased head simulation sessions during clinical practice course of stomatology.Additionally,87.5％of the students preferred head simulation training course to be applied in classic clinical clerkships.Conclusions There is strong demand among students of eight-year program of clinical medicine for incorporating head-simulator into the education of stomatology.The pilot simulation training received positive evaluations.Further exploration is needed to optimize specific scheduling and content arrangement.

AIM:This study investigates the apoptotic and autophagic effects of atractylodin on lung cancer cells,elucidating the underlying molecular mechanisms.METHODS:Non-small cell lung cancer(NSCLC)A549 and H460 cells,in addition to non-cancerous HBE cells,were cultured in vitro.The effects of atractylodin at various concen-trations on cell viability were assessed using CCK-8 assay.Apoptotic effects were evaluated through Hoechst staining and flow cytometry,while Western blot analysis was performed to detect changes in protein expressions associated with apopto-sis and autophagy,including P62,beclin-1,microtubule-associated protein 1 light chain 3(LC3),Kelch-like epichloro-hydrin(ECH)-associated protein-1(Keap-1),nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1).Autophagic flux was further analyzed using acridine orange(AO)stain-ing,and immunofluorescence for LC3 and Nrf2.Additionally,autophagy inhibition experiments were conducted using chloroquine(CQ),followed by analyses of autophagy and apoptosis.Reactive oxygen species(ROS)levels were quanti-fied using DCFH-DA.RESULTS:Treatment with atractylodin significantly reduced the viability of A549 and H460 lung cancer cells,promoting apoptosis and inducing autophagy.This was evidenced by an increase in acidic autophagic vesi-cles,upregulation of LC3 and beclin-1,and downregulation of P62.Inhibition of autophagy by chloroquine reversed atrac-tylodin-induced apoptosis.Moreover,atractylodin heightened ROS production,inhibited Keap-1,and stimulated the ex-pression of Nrf2,HO-1 and NQO1.CONCLUSION:Atractylodin effectively inhibits the proliferation of lung cancer cells by inducing apoptosis and autophagy.These effects are mediated through the modulation of the ROS/Nrf2/HO-1 sig-naling pathway,underscoring its potential as a therapeutic agent in lung cancer treatment.

Objective:Patients are breathing freely during adjuvant proton pencil beam radiotherapy after breast conserving surgery. Fluctuation of the thorax may affect the position of the end of the proton beam flow, which needs to be precisely evaluated on a millimeter scale.Methods:For 20 patients with breast cancer treated with proton radiotherapy after breast conserving surgery, PET-CT scan was performed approximately 10 min after the end of proton radiotherapy. The images of PET-CT were processed for ROI determination and sampling line (profile) extraction on a Raystation RV workstation to calculate the actual difference between the predicted and real radioactivity from the same spatial location as obtained by PET acquisition R50. Then, the differences in the spatial location between the actual process of proton irradiation and the planned process were obtained. Depth difference values for each pair of sampling lines were presented. Results:For 20 patients with breast cancer with a median follow-up of 22 months (range 12 - 46 months), all patients survived at the last follow-up, and no radiation pneumonitis was observed during the follow-up period. Among the verification results of 21 cases, the depth difference of evenly distributed was (-0.75±1.89) mm in the primary field and (-0.82±2.06) mm in the secondary field; The depth difference of sequential treatment was (1.81±1.87) mm in the primary field and (1.32±1.74) mm in the secondary field; The depth difference of synchronous addition in the primary field was (-1.47±1.44) mm, and the depth difference in the secondary field was (-1.48±2.11) mm.Conclusion:The results of off-line PET-CT in vivo biological verification show that the accuracy of the dose boundary cut-off was within 3 mm in breast cancer patients, which meets the clinical and physician requirement for the precision in breast cancer treatment.

We describe a case of fetal sacrococcygeal teratoma detected by ultrasound at 14 gestational weeks. The tumor was classified as "type Ⅰ" by ultrasonography combined with MRI. The cystic part accounted for over 60% of the mass before 26 weeks and ruptured spontaneously at 28 weeks. The size of the tumor was 12.8 cm×9.7 cm×12.3 cm at 36 +5 gestational weeks. A female newborn was born through cesarean section at 37 weeks of gestation and had the tumor removed surgically on the postnatal day 4. Postoperative follow-up showed that the neonate had a good prognosis without physiological dysfunction.

Objective:To explore the performance of the attention-multiple instance learning (MIL) framework, an attention fusion network-based MIL, in the automated diagnosis of chronic gastritis with multiple indicators.Methods:A total of 1 015 biopsy cases of gastritis diagnosed in Fudan University Cancer Hospital, Shanghai, China and 115 biopsy cases of gastritis diagnosed in Shanghai Pudong Hospital, Shanghai, China were collected from January 1st to December 31st in 2018. All pathological sections were digitally converted into whole slide imaging (WSI). The WSI label was based on the corresponding pathological report, including "activity" "atrophy" and "intestinal metaplasia". The WSI were divided into a training set, a single test set, a mixed test set and an independent test set. The accuracy of automated diagnosis for the Attention-MIL model was validated in three test sets.Results:The area under receive-operator curve (AUC) values of Attention-MIL model in single test sets of 240 WSI were: activity 0.98, atrophy 0.89, and intestinal metaplasia 0.98; the average accuracy of the three indicators was 94.2%. The AUC values in mixed test sets of 117 WSI were: activity 0.95, atrophy 0.86, and intestinal metaplasia 0.94; the average accuracy of the three indicators was 88.3%. The AUC values in independent test sets of 115 WSI were: activity 0.93, atrophy 0.84, and intestinal metaplasia 0.90; the average accuracy of the three indicators was 85.5%.Conclusions:To assist in pathological diagnosis of chronic gastritis, the diagnostic accuracy of Attention-MIL model is very close to that of pathologists. Thus, it is suitable for practical application of artificial intelligence technology.

Refractory pulmonary disease is a respiratory disease that seriously threatens the health of patients, and can lead to impaired pulmonary function and even respiratory failure.Currently, conventional drug therapy does not work well, so it is particularly important to find more effective treatments.Mesenchymal stem cells(MSCs) are a kind of multifunctional stem cells, which can promote the repair of damaged cells by regulating inflammatory and immune reactions and boost the regeneration of damaged tissues through paracrine.Therefore, MSCs are expected to provide a possibility for the treatment of refractory lung pulmonary diseases.

Objective:To summarize retrospectively the postoperative therapeutic effect of composite orbital fracture.Methods:587 patients with orbital fracture were assessed and diagnosed according to their clinical symptoms and 3D-CT reports before surgeries where incarcerated soft tissue is released and replaced thoroughly, with orbit reset as well as implants used to fix it, and then we evaluated the surgical outcomes by comparing the postoperative outlines of patients’ orbits, the functions of eyeballs along with their 3D-CT evidences.Results:After 10-month to 2-year postoperative follow-up, 12 cases of 587 who had apparent enophthalmos preoperatively still have slightly postoperative symptoms. Although the diplopia of 9 cases is partially recovered, their eye movement remain slightly restricted. In addition, the eye function of other patients didn’t dramatically decline in comparison with that of pre-trauma, except for those undergoing enucleation of eyeballs due to ophthalmorrhexis.Conclusions:Orbital fracture should be diagnosed and evaluated rigorously based on patients’ symptoms and 3D-CT reports, improving treatment effects by accurate reset, fixation and repair at early stage.

Objective:To summarize retrospectively the postoperative therapeutic effect of composite orbital fracture.Methods:587 patients with orbital fracture were assessed and diagnosed according to their clinical symptoms and 3D-CT reports before surgeries where incarcerated soft tissue is released and replaced thoroughly, with orbit reset as well as implants used to fix it, and then we evaluated the surgical outcomes by comparing the postoperative outlines of patients’ orbits, the functions of eyeballs along with their 3D-CT evidences.Results:After 10-month to 2-year postoperative follow-up, 12 cases of 587 who had apparent enophthalmos preoperatively still have slightly postoperative symptoms. Although the diplopia of 9 cases is partially recovered, their eye movement remain slightly restricted. In addition, the eye function of other patients didn’t dramatically decline in comparison with that of pre-trauma, except for those undergoing enucleation of eyeballs due to ophthalmorrhexis.Conclusions:Orbital fracture should be diagnosed and evaluated rigorously based on patients’ symptoms and 3D-CT reports, improving treatment effects by accurate reset, fixation and repair at early stage.