OBJECTIVE To prepare Arg-Gly-Asp（RGD）-modified doxorubicin （DOX）-loaded “core-shell” nanoparticles （RGD@DOX-LPNs）， characterize the nanoparticles， and investigate their antitumor effects. METHODS RGD@DOX-LPNs were prepared using the nanoprecipitation method. Their morphology was examined by visual inspection and electron microscopy. Particle size， polydispersity index （PDI）， and Zeta potential were determined， and differential scanning calorimetry （DSC） and X-ray diffraction （XRD） were employed. Encapsulation efficiency （EE）， drug loading （DL）， and stability were evaluated. The in vitro release kinetics， mucus diffusion， and tumor cell uptake [tracked using coumarin 6 （COU）] were investigated. The in vivo tissue distribution and gastrointestinal retention [labeled with 11-chloro-1， 1′-dipropyl-3， 3， 3′， 3′-tetramethyl-10， 12- trimethyleneindotricarbocyanine iodide （IR780）] were investigated. Using 4T1 tumor-bearing mice as the experimental subjects， the effects of the prepared formulation on tumor volume， tumor weight， and cell apoptosis rate were evaluated. RESULTS RGD@DOX-LPNs presented as orange transparent liquid with uniform and near-spherical particles. The particle size was （159.67± 8.02） nm， PDI was 0.15±0.06， and Zeta potential was （－19.70±0.79） mV. After modification with RGD， the thermal absorption peak and crystalline diffraction peak of DOX disappeared. EE and DL of RGD@DOX-LPNs were （72.65±4.37）% and （4.62± 0.38）% ， respectively. No obvious changes in appearance， particle size， or EE were observed after storage at 4 ℃ and 25 ℃ for 7 days. The cumulative drug release at 4 h was approximately 73%， which was lower than that of free DOX（almost completely released within 1 h）. The amount of COU in the first segmental mucus layer of COU-LPNs was significantly lower than that in the corresponding segment of RGD@COU- LPNs， whereas it was significantly higher in the 2nd to 5th segmental mucus layers compared to RGD@COU-LPNs （P＜0.01）. Cellular uptake of RGD@COU-LPNs was significantly higher than that of COU-LPNs（P＜0.05）. The isolated tissue fluorescence intensity of RGD@IR780-LPNs was stronger than that of IR780-LPNs， indicating better small intestinal retention. Compared with free DOX and unmodified nanoparticles （DOX-LPNs）， RGD@DOX-LPNs exhibited a higher tumor inhibition rate of 65.74%， significantly reduced tumor volume and weight， and increased apoptosis rate（P＜0.01）. CONCLUSIONS RGD@DOX-LPNs are successfully prepared with sustained release properties， which can improve gastrointestinal mucus retention， enhance cellular uptake of DOX， and have potent antitumor activity against breast cancer.

Objective:To develop a comprehensive training curriculum to enhance the effective implementation of the national initiative promoting dementia care and prevention.Methods:The Delphi method was utilized in an expert consultation that included 44 participants.The initial draft of the training curriculum was developed based on the current state of dementia care and prevention.This draft was subsequently evaluated for its importance, feasibility, and ease of dissemination.Experts offered targeted modifications and additional recommendations.Results:The recovery rate of the expert consultation questionnaire was 95.5%, with a recovery validity rate of 90.9%.The expert authority coefficient was 0.91, and the Kendall's coordination coefficient( W)for expert scoring was 0.316, with a significance level of P<0.001.Four course modules were ultimately identified: the foundation of memory clinic work, the complete management practice skills, group counseling techniques for caregivers, and practical skills for caregivers.The importance of these modules was rated with a mean of 4.92 to 4.95, and the coefficient of variation ranged from 0.044 to 0.063.Each module had a mean value of 4.92 to 4.95, with a coefficient of variation of 0.044 to 0.063; the mean value for practicality was between 4.78 and 4.92, with a coefficient of variation of 0.055 to 0.098; and the mean value for ease of generalization ranged from 4.28 to 4.65, with a coefficient of variation from 0.140 to 0.203.The four modules comprised a total of 55 specific course content items, with the mean value for each item ranging from 4.76 to 5.00 and a coefficient of variation from 0.000 to 0.121.The mean value of usefulness assigned to each entry ranged from 4.55 to 4.98, with a coefficient of variation from 0.031 to 0.150.Additionally, the mean value for ease of propagation assigned to each entry ranged from 4.00 to 4.83, with a coefficient of variation from 0.091 to 0.245. Conclusions:The developed training curriculum, which comprises four course modules and 55 items, demonstrated consistently high levels of importance, practicality, and ease of dissemination.These findings indicate that the curriculum is well-aligned with national initiatives aimed at enhancing dementia care and prevention.

Objective:To develop a deep learning model based on super-resolution endorectal ultrasound（ERUS）images for the preoperative prediction of perineural invasion（PNI）in patients with rectal cancer，thereby providing a reference for risk stratification and individualized treatment planning.Methods:A retrospective analysis was conducted on 382 patients with rectal cancer who underwent total mesorectal excision at Fujian Medical University Union Hospital between June 2019 and February 2024. Patients were randomly divided into a training set（ n=305）and a test set（ n=77）at a ratio of 8∶2，and further grouped into PNI-negative group and PNI-positive group subgroups based on pathological results. Super-resolution ultrasound images were generated from original ERUS images using a generative adversarial network（GAN）. Deep convolutional neural networks were developed based on features from intratumoral and peritumoral regions to identify the optimal region of interest（ROI）. The dSR5_ResNet18 and dSR5_ResNet50 models were constructed using the super-resolution images with a 5-pixel peritumoral extension. Representative clinical features were selected for subgroup analysis based on sample size and intergroup statistical differences between PNI-positive and PNI-negative patients. Forest plots were used to evaluate model applicability and robustness across subgroups. Results:The dSR5_ResNet18 model，built using super-resolution images of the tumor combined with a 5-pixel peritumoral region，achieved the best predictive performance，with an AUC of 0.867（95% CI=0.782 - 0.952）in the test set. Decision curve analysis demonstrated that the dSR5_ResNet18 model provided the greatest net clinical benefit. Forest plot analysis indicated strong generalizability of the models across subgroups such as pathological N stage，maximum lesion length，and lymph node enlargement，though relatively weaker performance was observed in the carcinoembryonic antigen（CEA）subgroup. Among all models，dSR5_ResNet18 exhibited the most consistent performance across subgroups，with the narrowest confidence intervals and highest robustness. Conclusions:The deep learning model incorporating ERUS-based super-resolution reconstruction demonstrated excellent performance in the preoperative prediction of PNI in rectal cancer. It offers significant advantages in image quality and generalizability，and may serve as a valuable tool to assist clinicians in formulating personalized treatment strategies.

Objective: To investigate the therapeutic effect of bone marrow mesenchymal stem cells ( BMSCs) mod- ified by bone morphogenetic protein ( BMP) -2 gene combined with nano-hydroxyapatite ( nHA) / polyamide 66 ( PA66) on femoral nonunion in rats． Methods : Rat BMSCs were isolated and divided into the stent + BMSCs group，stent + BMSCs + rhBMP-2 group，and stent + BMSCs + Ad-BMP-2 group; human recombinant BMP-2 ( rh- BMP-2) or adenovirus-infected BMP-2 ( Ad-BMP-2) vector was transfected into BMSCs and loaded onto nHA / PA66 stent materials．Flow cytometry was used to detect that BMSCs expressed specific surface markers．Cell pro- liferation was detected by MTT assay，related bioactive factors［platelet-derived growth factor ( PDGF) ，transfor- ming growth factor-β ( TGF-β) ，vascular endothelial growth factor ( VEGF) ，fibroblast growth factor ( FGF) ，os- teocalcin ( OCN) ，osteonectin ( ON) ］were detected by ELISA，alkaline phosphatase ( ALP) activity was detec- ted，and cell growth and adhesion were observed by scanning electron microscopy ( SEM) ．In the atrophic nonun- ion model of SD rats，the stent + BMSCs + rhBMP-2 or stent + BMSCs + Ad-BMP-2 complex was implanted into the defect area，which was divided into the rhBMP-2 group and the Ad-BMP-2 group，and the therapeutic effect was e- valuated by X-ray and MicroCT． Results: The surface of the nHA / PA66 stent was smooth and porous，and BMSCs adhered well．Flow cytometry showed high expression of CD29 and CD90 and low expression of CD45 and CD34 in BMSCs．MTT showed that the cells proliferated rapidly after 72 h．Compared with the stent + BMSCs group and the stent + BMSCs + rhBMP-2 group，the ALP activity，the expressions of PDGF，TGF-β , VEGF，FGF，OCN，and ON in the stent + BMSCs + Ad-BMP-2 group were significantly up-regulated ( P＜0. 05) ．12 weeks after surgery， the stent complex in the Ad-BMP-2 group of rats was completely wrapped by newly formed cortical bone，and the surface was smooth and intact．X-ray showed that the complex in the Ad-BMP-2 group was completely wrapped by newly formed cortical bone，and the recovery degree was better than that in the rhBMP-2 group．Micro-CT results showed that compared with the rhBMP-2 group，the bone volume fraction，trabecular thickness，trabecular num- ber，bone mineral density，and bone mineral content in the Ad-BMP-2 group all increased 12 weeks after surgery ( P＜0. 05) ，and the trabecular separation level decreased ( P＜0. 05) ． Conclusion Ad-BMP-2-transfected BM- SCs combined with nHA / PA66 stent material can express bioactivity more effectively，provide a continuous and good microenvironment for the proliferation and differentiation of BMSCs，which is beneficial to promoting local os- teogenic activity and bone defect repair．

Objective To investigate the impact of recent rhythmic interventions on the depth of sedation during anesthesia induction in patients undergoing general anesthesia with remazolam toluene sulfonate.Methods Patients aged 18～65 years who underwent elective surgery under general anesthesia were selected and divided into a day group(7:00～19:00)and a night group(19:00～7:00 the following day)based on the start time of anesthesia induction.Each group comprised 70 patients,further subdivided into five equal dose groups of remazolam toluene sulfonate at 0.11,0.13,0.16,0.18,and 0.22 mg/kg,with 14 patients in each subgroup.The Modified Observer's Assessment of Alertness/Sedation(MOAA/S)score and Bispectral Index(BIS)value were recorded 3 minutes post-administration,and the correlation coefficient between these two parameters was calculated.The induction dose and unit body weight dose of remazolam toluene sulfonate were documented when the MOAA/S score was≤1.Addition-ally,the induction dose of remazolam for both day and night groups as well as for patients of different genders was recorded.The half effective dose(ED50),95％effective dose(ED95),and 95％confidence interval(CI)for both the day and night groups were also calculated.Results When MOAA/S≤1,the induced dose of remazolam in the night group(12.34±3.51)mg was significantly lower than that in the day group(13.98±4.21)mg.Additionally,the dose per unit body weight of remazolam in the night group(0.20±0.049)mg/kg was also significantly lower than that in the day group(0.22±0.056)mg/kg.Statistically significant differences were observed in the ED50 and ED95 values of remazolam between the day and night groups(P<0.05).The correlation coefficient between BIS and MOAA/S was 0.902(95％CI:0.876～0.925)in the day group and 0.905(95％CI:0.879～0.929)in the night group,indicating a strong correlation between MOAA/S and BIS in both groups.However,there was no significant difference in the correlation coefficients between the two groups(P>0.05).The correlation coefficients between BIS and MOAA/S were 0.763(95％CI:0.726～0.799)in the daytime group and 0.777(95％CI:0.739～0.808)in the nighttime group.In a separate analysis,the correlation coefficients were 0.768(95％CI:0.723～0.804)for the day-time group and 0.771(95％CI:0.723～0.811)for the nighttime group.A strong correlation was observed between MOAA/S and BIS in both male and female patients during both day and night,with no significant difference in corre-lation coefficients between groups(P>0.05).However,BIS values were significantly lower in the nighttime group compared to the daytime group(P<0.05).Additionally,male patients required a higher total induced dose of rem-azolam than female patients during both day and night,with this difference being statistically significant(P<0.05).Furthermore,female patients exhibited a significant decrease in BIS values at night(P<0.05).Conclusions Recent studies have shown that circadian rhythm significantly influences anesthesia-induced sedation in patients undergoing general anesthesia with remazolam toluenesulfonate.Specifically,the sedation effect is more pronounced in nighttime procedures,and there is a notable gender difference,with female patients exhibiting better sedation outcomes during nighttime surgeries.

Objective:To investigate the clinicopathological features, treatment-effect assessment and prognosis of SMARCA4-deletion non-small cell lung cancer (NSCLC) that was treated with neoadjuvant therapy.Methods:Eleven consecutive cases of SMARCA4-deletion NSCLC treated with neoadjuvant therapy in Guangdong Provincial People′s Hospital, Guangzhou, China from January 2007 to October 2024 were collected. Their clinicopathological features, pathological assessment of treatment effect, and prognosis were retrospectively analyzed.Results:All the 11 patients were male. Their median age at diagnosis was 56 (49,64) years. Nine patients were smokers (9/11). Ten patients received neoadjuvant chemoimmunotherapy, and one received neoadjuvant targeted therapy. Eleven biopsy samples showed SMARCA4 complete loss, including 7 cases of invasive non-mucinous adenocarcinoma, 1 case of invasive mucinous adenocarcinoma, 1 case of non-keratinizing squamous cell carcinoma, and 2 cases of NSCLC, not otherwise specified. The histological response to neoadjuvant therapy in resected specimens varied, including tumor necrosis, foam cell aggregation, cholesterol clefts, immune cell infiltrates, reactive granulomas, and stromal fibrosis. Three cases of the primary lesion achieved major pathological response (MPR), and 2 cases achieved complete pathological response (CPR). The MPR rate of neoadjuvant chemoimmunotherapy was 3/10 while its CPR ratio was 2/10. Of the 9 resected specimens that did not achieve CPR, 5 showed a post-treatment histological type different from the pre-treatment one. Eight tumors showed complete SMARCA4 loss, while 1 showed heterogeneous expression. Of the 11 biopsy specimens examined using next generation sequencing, 9 cases showed class 1 SMARCA4 mutations (including 7 nonsense mutations and 2 acquired nonsense mutations), and 2 cases showed wild-type SMARCA4. Taking immunohistochemistry as the gold standard, the sensitivity of next generation sequencing for the detection of SMARCA4-deletion NSCLC was 9/11. After follow-up of 6.9 to 46.6 months, five patients experienced postoperative recurrence, and 6 patients were disease free. The disease-free survival ranged from 0.7 to 27.5 months (median, 7.6 months).Conclusions:The surgical specimens of SMARCA4-deletion NSCLC with neoadjuvant therapy show varying degrees of treatment response. The tumor components sensitive to chemoimmunotherapy and targeted therapy are mostly adenocarcinoma and squamous cell carcinoma, while large cell carcinoma, spindle cell carcinoma and giant cell carcinoma are relatively less sensitive to treatment. Assessment of MPR and CPR suggests that some NSCLC patients with SMARCA4-deletion can benefit from neoadjuvant therapy.

Objective:To investigate the clinicopathological features, treatment-effect assessment and prognosis of SMARCA4-deletion non-small cell lung cancer (NSCLC) that was treated with neoadjuvant therapy.Methods:Eleven consecutive cases of SMARCA4-deletion NSCLC treated with neoadjuvant therapy in Guangdong Provincial People′s Hospital, Guangzhou, China from January 2007 to October 2024 were collected. Their clinicopathological features, pathological assessment of treatment effect, and prognosis were retrospectively analyzed.Results:All the 11 patients were male. Their median age at diagnosis was 56 (49,64) years. Nine patients were smokers (9/11). Ten patients received neoadjuvant chemoimmunotherapy, and one received neoadjuvant targeted therapy. Eleven biopsy samples showed SMARCA4 complete loss, including 7 cases of invasive non-mucinous adenocarcinoma, 1 case of invasive mucinous adenocarcinoma, 1 case of non-keratinizing squamous cell carcinoma, and 2 cases of NSCLC, not otherwise specified. The histological response to neoadjuvant therapy in resected specimens varied, including tumor necrosis, foam cell aggregation, cholesterol clefts, immune cell infiltrates, reactive granulomas, and stromal fibrosis. Three cases of the primary lesion achieved major pathological response (MPR), and 2 cases achieved complete pathological response (CPR). The MPR rate of neoadjuvant chemoimmunotherapy was 3/10 while its CPR ratio was 2/10. Of the 9 resected specimens that did not achieve CPR, 5 showed a post-treatment histological type different from the pre-treatment one. Eight tumors showed complete SMARCA4 loss, while 1 showed heterogeneous expression. Of the 11 biopsy specimens examined using next generation sequencing, 9 cases showed class 1 SMARCA4 mutations (including 7 nonsense mutations and 2 acquired nonsense mutations), and 2 cases showed wild-type SMARCA4. Taking immunohistochemistry as the gold standard, the sensitivity of next generation sequencing for the detection of SMARCA4-deletion NSCLC was 9/11. After follow-up of 6.9 to 46.6 months, five patients experienced postoperative recurrence, and 6 patients were disease free. The disease-free survival ranged from 0.7 to 27.5 months (median, 7.6 months).Conclusions:The surgical specimens of SMARCA4-deletion NSCLC with neoadjuvant therapy show varying degrees of treatment response. The tumor components sensitive to chemoimmunotherapy and targeted therapy are mostly adenocarcinoma and squamous cell carcinoma, while large cell carcinoma, spindle cell carcinoma and giant cell carcinoma are relatively less sensitive to treatment. Assessment of MPR and CPR suggests that some NSCLC patients with SMARCA4-deletion can benefit from neoadjuvant therapy.

Objective To investigate the impact of recent rhythmic interventions on the depth of sedation during anesthesia induction in patients undergoing general anesthesia with remazolam toluene sulfonate.Methods Patients aged 18～65 years who underwent elective surgery under general anesthesia were selected and divided into a day group(7:00～19:00)and a night group(19:00～7:00 the following day)based on the start time of anesthesia induction.Each group comprised 70 patients,further subdivided into five equal dose groups of remazolam toluene sulfonate at 0.11,0.13,0.16,0.18,and 0.22 mg/kg,with 14 patients in each subgroup.The Modified Observer's Assessment of Alertness/Sedation(MOAA/S)score and Bispectral Index(BIS)value were recorded 3 minutes post-administration,and the correlation coefficient between these two parameters was calculated.The induction dose and unit body weight dose of remazolam toluene sulfonate were documented when the MOAA/S score was≤1.Addition-ally,the induction dose of remazolam for both day and night groups as well as for patients of different genders was recorded.The half effective dose(ED50),95％effective dose(ED95),and 95％confidence interval(CI)for both the day and night groups were also calculated.Results When MOAA/S≤1,the induced dose of remazolam in the night group(12.34±3.51)mg was significantly lower than that in the day group(13.98±4.21)mg.Additionally,the dose per unit body weight of remazolam in the night group(0.20±0.049)mg/kg was also significantly lower than that in the day group(0.22±0.056)mg/kg.Statistically significant differences were observed in the ED50 and ED95 values of remazolam between the day and night groups(P<0.05).The correlation coefficient between BIS and MOAA/S was 0.902(95％CI:0.876～0.925)in the day group and 0.905(95％CI:0.879～0.929)in the night group,indicating a strong correlation between MOAA/S and BIS in both groups.However,there was no significant difference in the correlation coefficients between the two groups(P>0.05).The correlation coefficients between BIS and MOAA/S were 0.763(95％CI:0.726～0.799)in the daytime group and 0.777(95％CI:0.739～0.808)in the nighttime group.In a separate analysis,the correlation coefficients were 0.768(95％CI:0.723～0.804)for the day-time group and 0.771(95％CI:0.723～0.811)for the nighttime group.A strong correlation was observed between MOAA/S and BIS in both male and female patients during both day and night,with no significant difference in corre-lation coefficients between groups(P>0.05).However,BIS values were significantly lower in the nighttime group compared to the daytime group(P<0.05).Additionally,male patients required a higher total induced dose of rem-azolam than female patients during both day and night,with this difference being statistically significant(P<0.05).Furthermore,female patients exhibited a significant decrease in BIS values at night(P<0.05).Conclusions Recent studies have shown that circadian rhythm significantly influences anesthesia-induced sedation in patients undergoing general anesthesia with remazolam toluenesulfonate.Specifically,the sedation effect is more pronounced in nighttime procedures,and there is a notable gender difference,with female patients exhibiting better sedation outcomes during nighttime surgeries.

Objective:To develop a comprehensive training curriculum to enhance the effective implementation of the national initiative promoting dementia care and prevention.Methods:The Delphi method was utilized in an expert consultation that included 44 participants.The initial draft of the training curriculum was developed based on the current state of dementia care and prevention.This draft was subsequently evaluated for its importance, feasibility, and ease of dissemination.Experts offered targeted modifications and additional recommendations.Results:The recovery rate of the expert consultation questionnaire was 95.5%, with a recovery validity rate of 90.9%.The expert authority coefficient was 0.91, and the Kendall's coordination coefficient( W)for expert scoring was 0.316, with a significance level of P<0.001.Four course modules were ultimately identified: the foundation of memory clinic work, the complete management practice skills, group counseling techniques for caregivers, and practical skills for caregivers.The importance of these modules was rated with a mean of 4.92 to 4.95, and the coefficient of variation ranged from 0.044 to 0.063.Each module had a mean value of 4.92 to 4.95, with a coefficient of variation of 0.044 to 0.063; the mean value for practicality was between 4.78 and 4.92, with a coefficient of variation of 0.055 to 0.098; and the mean value for ease of generalization ranged from 4.28 to 4.65, with a coefficient of variation from 0.140 to 0.203.The four modules comprised a total of 55 specific course content items, with the mean value for each item ranging from 4.76 to 5.00 and a coefficient of variation from 0.000 to 0.121.The mean value of usefulness assigned to each entry ranged from 4.55 to 4.98, with a coefficient of variation from 0.031 to 0.150.Additionally, the mean value for ease of propagation assigned to each entry ranged from 4.00 to 4.83, with a coefficient of variation from 0.091 to 0.245. Conclusions:The developed training curriculum, which comprises four course modules and 55 items, demonstrated consistently high levels of importance, practicality, and ease of dissemination.These findings indicate that the curriculum is well-aligned with national initiatives aimed at enhancing dementia care and prevention.