ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

This paper summarizes professor BAI Yanping's clinical experience in treating rosacea. It is believed that stagnant heat in cutaneous collaterals serves as the core pathogenesis of rosacea， and the interbinding of static blood and heat as well as blockage of cutaneous collaterals constitute the key pathological links. The core therapeutic principles consist of nourishing blood， activating blood circulation to resolve stasis， clearing heat， relieving stagnation and unblocking collaterals. In clinic， Wenqing Decoction （温清饮） is adopted as the basic formula， with flexible modifications according to distinct clinical syndromes and stages of rosacea. Based on clinical syndromes， for erythematotelangiectatic rosacea， the treatment should focus on activating blood to unblock collaterals， clearing heat and cooling blood； for papulopustular rosacea， the treatment should focus on clearing heat and resolving toxins， and resolving stasis and dissipating masses； for hypertrophic phymatous rosacea， the treatment should simultaneously softening hard masses， dissipating stagnation， nourishing blood and moisturizing the skin； for ocular rosacea， the treatment should prioritize clearing liver heat to improve eyesight， unblocking orifices and eliminating heat. Based on the stages， in acute phase， heat-clearing， detoxifying and blood-cooling therapies are emphasized； for protracted chronic phase， concurrent regulation of static blood and heat plus blood-nourishing and collateral-unblocking methods are applied； the consolidation stage targets invigorating the spleen and replenishing qi to strengthen vital resistance and eliminate pathogenic factors. Meanwhile， precise compatibility of aromatic medicinals， blood-level medicinals and channel-guiding medicinals is highly valued. The therapy should balance systemic regulation and local lesion care， and combine internal and external treatment， which may provides clinical references for TCM intervention of rosacea.

This paper summarizes professor BAI Yanping's clinical experience in treating rosacea. It is believed that stagnant heat in cutaneous collaterals serves as the core pathogenesis of rosacea， and the interbinding of static blood and heat as well as blockage of cutaneous collaterals constitute the key pathological links. The core therapeutic principles consist of nourishing blood， activating blood circulation to resolve stasis， clearing heat， relieving stagnation and unblocking collaterals. In clinic， Wenqing Decoction （温清饮） is adopted as the basic formula， with flexible modifications according to distinct clinical syndromes and stages of rosacea. Based on clinical syndromes， for erythematotelangiectatic rosacea， the treatment should focus on activating blood to unblock collaterals， clearing heat and cooling blood； for papulopustular rosacea， the treatment should focus on clearing heat and resolving toxins， and resolving stasis and dissipating masses； for hypertrophic phymatous rosacea， the treatment should simultaneously softening hard masses， dissipating stagnation， nourishing blood and moisturizing the skin； for ocular rosacea， the treatment should prioritize clearing liver heat to improve eyesight， unblocking orifices and eliminating heat. Based on the stages， in acute phase， heat-clearing， detoxifying and blood-cooling therapies are emphasized； for protracted chronic phase， concurrent regulation of static blood and heat plus blood-nourishing and collateral-unblocking methods are applied； the consolidation stage targets invigorating the spleen and replenishing qi to strengthen vital resistance and eliminate pathogenic factors. Meanwhile， precise compatibility of aromatic medicinals， blood-level medicinals and channel-guiding medicinals is highly valued. The therapy should balance systemic regulation and local lesion care， and combine internal and external treatment， which may provides clinical references for TCM intervention of rosacea.

OBJECTIVE To investigate the clinical efficacy of mepolizumab as postoperative maintenance therapy after endoscopic sinus surgery （ESS） in patients with eosinophilic chronic rhinosinusitis with nasal polyps （EosCRSwNP）.METHODS A retrospective cohort study was conducted to collect clinical data from patients with EosCRSwNP who underwent ESS at the Dept. of Otolaryngology in Xuzhou First People’s Hospital， from January 1 to May 31， 2025. Patients were divided into a control group （56 cases， treated with intranasal corticosteroids postoperatively） and an observation group （51 cases， treated with mepolizumab postoperatively） based on their postoperative maintenance therapy regimens. The nasal function parameters [nasal cavity volume （NCV）， distance from the minimum cross-sectional area to the anterior nostril （DCAN）， nasal minimum cross-sectional area （NMCA）， saccharin clearance time， nasal mucociliary clearance rate， mucociliary clearance velocity]， and the indicators related to nasal mucosal remodeling [peripheral blood eosinophil （EOS） percentage， serum levels of transforming growth factor-β 1 （TGF-β 1 ） and vascular endothelial growth factor （VEGF）] were compared between the two groups at 2 weeks and 3， 6 months after surgery. The assessment indicators of the inflammation status of nasal mucositis [modified Lund-Kennedy Endoscopic Scoring System （MLK） score]， the degree of nasal polyp recurrence[nasal polyp score （NPS）]， and the quality of life [Sino-nasal Outcome Test-20 （SNOT-20） score] were compared at 2 weeks and 6 months after surgery. Adverse events were also recorded and compared between the two groups.RESULTS At 2 weeks after surgery， there were no statistically significant differences in the aforementioned indicators/scores between the two groups （ P ＞0.05）. Compared with the same group at 2 weeks postoperatively， both groups showed significant increases in NCV， NMCA， nasal mucociliary clearance rate， and mucociliary clearance velocity at 3 and 6 months postoperatively； significant decreases or reductions were observed in DCAN， saccharin clearance time， EOS percentage， TGF-β 1 and VEGF levels at 3 and 6 months postoperatively， while in MLK score， NPS， SNOT-20 score were all significantly reduced or shortened （ P ＜0.05）. Furthermore， the improvements in these indicators in the observation group were significantly greater than those in the control group during the same time periods （ P ＜0.05）. The overall incidence of adverse reactions was comparable between the two groups （ P ＞0.05）， but the incidence of injection-site reactions was significantly higher in the observation group than in the control group （ P ＜0.05）.CONCLUSIONS The use of mepolizumab for postoperative maintenance therapy following ESS in patients with EosCRSwNP promotes the recovery of nasal function， improves indicators of nasal mucosal remodeling， reduces inflammation， lowers polyp score， and enhances quality of life. Its efficacy is superior to that of intranasal corticosteroids； however， clinicians should be mindful of the risk of injection-site reactions of mepolizumab.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Objective To test the longitudinal mediating mechanism of kinesophobia between family functioning and exercise adherence in elderly patients with postoperative adjacent vertebral re-fracture after osteoporotic vertebral compression fracture(OVCF).Methods Convenience sampling method was used to admit to the Department of Orthopaedics of a tertiary hospital in Xuzhou City with adjacent vertebral re-fracture after OVCF were conveniently selected as the survey subjects,and longitudinal investigation was conducted using the APGAR,Functional Exercise Adherence Scale,and TSK Scale.Unconditional potential growth model,structural equation and Bootstrap method were used for statistical analysis.Results A total of 232 valid questionnaires were collected.Longitudinal mediation modeling revealed that the intercept of family functioning significantly negatively predicted the intercept of kinesophobia(β=-0.456,P＜0.001)and the slope of family functioning significantly negatively predicted the slope of kinesophobia(β=-0.962,P＜0.001).The intercept for kinesophobia significantly negatively predicted the intercept for exercise adherence(β=-0.623,P＜0.001)and significantly negatively predicted the slope for exercise adherence(β=-0.354,P=0.013).Conclusion The initial level and rate of development of kinesophobia play a fully longitudinal mediating role in the development of family functioning on exercise adherence.Medical professionals should assess and manage patients'family functioning and kinesophobia in a timely manner,and rationally utilize their interrelationships to improve the level of exercise adherence as much as possible.

Objective:To evaluate the short-term efficacy of endoscopic-laparoscopic regional gastric resection combined with sentinel lymph node basin dissection in patients with early-stage gastric cancer.Methods:This is a retrospective case series study. Data of 17 consecutive early gastric cancer patients from a prospective cohort at Beijing Friendship Hospital,Capital Medical University were analyzed between August 2023 and August 2024. Sixteen cases were from the department of general surgery and 1 from the department of gastroenterology. The cohort included 9 males and 8 females,with a mean age of 61.4 years (range: 46 to 79 years). Clinical data,including demographics,pathological features,surgical procedures,and follow-up outcomes,were collected through medical records and databases. All patients were followed for over 3 months,with follow-up ending on December 5,2024.Results:A total of 17 patients were involved. Among them, 5 patients underwent endoscopic submucosal dissection (ESD) combined with laparoscopic sentinel lymph node dissection (LSBD),and another 3 patients who underwent complete ESD resection received LSBD due to pathological stage meeting the expanded indications. 6 patients who underwent non-curative ESD resection received laparoscopic gastric regional resection (LRG) combined with LSBD,and another 3 patients directly received LRG combined with LSBD. The average number of sentinel lymph nodes dissected before surgery ( M(IQR)) was 8.9 (4.5) (range: 4 to 21),and the detection rate and accuracy rate were both 100%. Postoperative pathology confirmed that there was no metastasis in the sentinel lymph nodes of 5 patients who underwent ESD combined with LSBD and 3 patients who underwent LSBD after complete ESD resection. The vertical and horizontal margins of ESD were all negative. One patient was an absolute indication for ESD. For the 6 patients who underwent non-curative ESD resection combined with LRG and LSBD,the horizontal margins were all negative. Two patients showed 1 metastasis in each of the 21 and 9 sentinel lymph nodes during the operation,and additional distal gastrectomy was performed during the operation. Postoperatively,73 and 39 lymph nodes were retrieved respectively. The former had 1 additional metastasis,while the latter had no metastasis. Among the 3 patients who underwent direct LRG combined with LSBD,the horizontal margins were negative. One patient was confirmed as an absolute indication for ESD by postoperative pathology,and one patient had 1 metastasis in 8 sentinel lymph nodes during the operation,and additional distal gastrectomy was performed. Postoperatively,there was no metastasis in 54 lymph nodes. All patients had no complications such as infection,bleeding,perforation,or death after surgery. Among the 14 patients who did not receive additional radical surgery,they were able to pass gas and defecate within 3 days after surgery,with an average hospital stay of 6 days. The nutritional indicators and gastric radionuclide emptying imaging half-emptying time were similar to those before surgery at 3 months after surgery. Conclusions:Laparoscopic and endoscopic cooperative regional gastrectomy with sentinel lymph node basin dissection has the advantages of minimal invasiveness,preservation of gastric function,and precise treatment. It maybe suitable for patients with early-stage gastric cancer at high risk of lymph node metastasis and has good short-term efficacy.

With the increasing attention of domestic and foreign scholars to death with dignity, the importance of death with dignity in the field of hospice care is becoming increasingly prominent. This study reviews the fundamental concept of death with dignity, comprehensively analyzes the content, application scenarios, advantages, and limitations of various cognition and practice assessment tools for death with dignity at home and abroad, aiming to provide reference for promoting the development and appropriate use of cognition and practice assessment tools for death with dignity in China.

Objective To mine the risk signals of adverse drug events(ADEs)related to lecanemab through the U.S.Food and Drug Adminstration Adverse Event Reporting System(FAERS)database,to provide a reference for the safe clinical use of lecanemab.Methods Data on adverse events related to lecanemab from the fourth quarter,2010 to the second quarter 2024 in the FAERS were collected.Potential ADE signals were mined using the reporting odds ratio(ROR)method,Medicines and Healthcare Products Regulatory Agency(MHRA)method,Bayesian confidence propagation neural network(BCPNN)method and multi-item gamma Poisson shrinker(MGPS)method.The top 30 ADEs in terms of report frequency and signal strength,as well as ADEs categorized by system organ class(SOC),were statistically analyzed.Results A total of 868 adverse event reports related to lecanemab were collected,involving 1,986 instances of ADEs with 38 related ADE identified,the proportion of serious ADEs was 23.39％,and 87.15％of ADEs occurred in the first 3 months after the initiation of the drug.The top 30 PT signals in reported cases were headache,chills,fatigue,effusion type amyloid-related imaging abnormalities(ARIA-E),hemorrhage-type amyloid-related imaging abnormalities(ARIA-H),and so on.The top 30 signals in terms of signal intensity mainly included ARIA-E,ARIA-H,brain fog,infusion-related reactions.ADEs related to nervous system diseases were the most common.Fifteen new suspected or serious ADEs not recorded in the instructions were discovered,such as brain fog,formication,status epilepticus.Conclusion Risk assessment of patients'medication should be conducted before clinical use of lecanemab,especially in the first 3 months of the medication period,focus should be placed on monitoring common ADEs,such as ARIA-E,ARIA-H,infusion-related reactions.Attention also needs to be paid to the newly discovered suspected ADEs,to ensure the patients'medication safety.