[摘 要] 目的：构建负载STING激动剂DMXAA的锰卟啉金属有机框架纳米颗粒（DPM），探讨其对三阴性乳腺癌（TNBC）细胞4T1及其小鼠移植瘤的治疗效果。方法：通过物理吸附法制备 DPM 纳米颗粒，利用透射电镜、扫描电镜及纳米粒度电位仪表征其形貌与理化性质。常规培养4T1细胞，细胞实验分为对照组、超声辐照组（US组）、DPM治疗组（DPM组）和DPM治疗联合超声辐照组（DPM + US组），用CCK-8法检测细胞活性，免疫荧光法检测高迁移率族蛋白B1（HMGB1）和钙网蛋白（CRT）的表达，WB法检测STING通路相关蛋白的表达。构建4T1细胞移植瘤小鼠模型，分为四组，处理同细胞实验，测量肿瘤体积，免疫荧光法检测移植瘤组织中Ki-67、HMGB1、CRT和缺氧诱导因子-1ɑ（HIF-1ɑ）蛋白的表达，TUNEL法检测细胞凋亡，流式细胞术检测免疫细胞活化情况，对主要器官进行H-E染色，以评估纳米材料的体内安全性。结果：DPM呈梭形，平均粒径（268 ± 3.302）nm，电位（33.1 ± 0.87）mV。细胞实验中，DPM联合超声辐照可明显抑制4T1细胞的增殖（P < 0.001），提高4T1细胞中ROS水平（P < 0.001），诱导4T1细胞CRT表达上调（P < 0.001），HMGB1从细胞核中移至细胞质，激活STING信号通路[p-STING、p-TBK1、p-IRF3蛋白表达均显著增加（均P < 0.001）]。体内实验中，DPM联合超声辐照可显著抑制4T1细胞移植瘤生长（P < 0.001）并促进免疫细胞表型转化（P < 0.001），抑制移植瘤组织中Ki-67、HIF-1α蛋白表达（均P < 0.01），谷胱甘肽（GSH）产生（P < 0.01），促进CRT、HMGB1蛋白表达、ROS产生（P < 0.001），对主要器官结构无明显影响。结论： DPM联合超声辐照可通过激活STING通路显著抑制4T1细胞及其移植瘤的生长，诱导抗肿瘤免疫应答，且对主要器官无明显毒性。

OBJECTIVE To investigate the prevalence and influencing factors of potentially inappropriate medication （PIM） among the elderly in nursing homes in Urumqi based on three PIM screening tools， and to compare the applicability of different tools. METHODS A cross-sectional study design was adopted. Elderly individuals from six nursing homes in Urumqi were selected as the research subjects from May 2021 to September 2023. Demographic characteristics， disease burden and medication records of the elderly were collected. PIM screening was performed using the Chinese PIM criteria （2024 edition）， the American Geriatrics Society （AGS） Beers criteria （2023 edition）， and the Screening Tool of Older Person’S Prescriptions（STOPP）/Screening Tool to Alert to Right Treatment（START） （2023 edition）. Fleiss’s Kappa test was used to assess the consistency among the three screening tools， and multivariate Logistic regression was used to analyze the influencing factors of PIM. RESULTS The prevalence of PIM screened by the Chinese PIM criteria was 47.4% （323/682）， by the AGS Beers criteria was 43.4% （296/682）， and by the STOPP criteria was 50.9% （347/682）. The consistency among the three screening tools was low （Fleiss’s Kappa＝0.12， P ＜0.001）. Multivariate Logistic regression analysis showed that all three screening tools indicated that polypharmacy， aspirin use and psychotropic drug use were independent risk factors for PIM among elderly in nursing houses （all OR＞1， P ＜0.05）. CONCLUSIONS The prevalence of PIM among the elderly in nursing homes in Urumqi is relatively high. Polypharmacy， aspirin use and psychotropic drug use are common independent risk factors for PIM. There are differences in screening results among the three tools with low consistency. The Chinese PIM criteria can serve as a first-line tool for PIM screening in nursing homes.

OBJECTIVE To construct a pharmaceutical care framework suitable for elderly individuals in nursing homes， so as to provide standardized content guidance for relevant practice. METHODS The initial items of pharmaceutical care content in n ursing homes were drafted through literature research and semi-structured interviews. Delphi method was used to conduct correspondence consultation among 38 experts from related fields in Xinjiang. The expert positive coefficient， authority coefficient， and Kendall’s W were calculated， and the analytic hierarchy process was employed to determine the weight of each item. After thorough discussion among the research team members， the pharmaceutical care framework suitable for elderly individuals provided by hospital pharmacists collaborating with nursing homes was finalized. RESULTS The questionnaire recovery rates for both rounds of expert correspondence consultation were 100%， with an authority coefficient ＞0.8 and Kendall’s W ranging between 0.153 and 0.185 （ P ＜0.001）. A total of 7 primary items and 31 secondary items were ultimately determined， with the consistency ratio of the item weights all being less than 0.1. Based on the integration of importance and feasibility， among the primary items， “assessment of pharmaceutical care needs” was assigned the highest weight. Among the secondary items， highly practical items such as “survey of pharmaceutical care needs”“guidance on usage and dosage”“methods for correctly reading drug package inserts”， and “self-management of common chronic diseases in the elderly” were assigned relatively high comprehensive weights. CONCLUSIONS The pharmaceutical care framework suitable for elderly individuals provided by hospital pharmacists collaborating with nursing homes， which was constructed based on the Delphi method， demonstrates good scientific validity and reliability， and can serve as a reference for pharmacists to provide pharmaceutical care in nursing homes.

ObjectiveTo investigate the antiviral efficacy of pegylated interferon α-2b （PEG-IFN-α-2b） in patients with HBV-related liver cirrhosis， to assess the safety and tolerability of this regimen， and to provide evidence-based medical evidence for optimizing the treatment strategies for patients with HBV-related compensated liver cirrhosis. MethodsA prospective study was conducted among 115 patients with HBV-related compensated liver cirrhosis and 114 patients with CHB who attended Third People’s Hospital of Taiyuan from January 2023 to March 2024. Treatment-naïve patients received PEG-IFN-α-2b monotherapy， while the patients once treated with nucleos（t）ide analogues （NAs） received PEG-IFN-α-2b add-on therapy. The patients with HBV-related compensated liver cirrhosis were followed up at baseline and at 12， 24， 36， and 48 weeks of treatment. Samples were collected from CHB patients at baseline and at the end of follow-up to assess virological indicators， routine blood test results， and liver function. The chi-square test was used for comparison of categorical data between groups； the independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the one-way repeated measures analysis of variance was used for comparison among different time ponts within the same group，and the Bonferroni was applied for post-hoc pairwise comparisons； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Friedman test was used for comparison across different time points within the same group， and the Nemenyi test was utilized for subsequent pairwise comparisons. The multivariate stepwise Logistic regression analysis was used to investigate the influencing factors for clinical cure. ResultsCompared with the CHB group， the HBV-related compensated liver cirrhosis group had a significantly higher mean age （43.50±9.97 years vs 40.90±8.16 years， t=2.160， P=0.032）， a significantly higher proportion of patients with hepatitis B e antigen at baseline （28.70% vs 15.79%， χ²=4.788， P=0.029）， and a significantly lower platelet level ［（178.67±55.07）×10⁹/L vs （194.93±55.79）×10⁹/L， t=2.217， P=0.028］. Compared with the CHB group at the end of follow-up， the HBV-related compensated liver cirrhosis group had significantly lower HBV surface antigen （HBsAg） clearance rate （10.38% vs 33.04%， χ²=14.988， P<0.001） and HBV surface antibody positive rate （0.00% vs 19.64%， χ²=21.041， P<0.001）. Compared with the CHB group at the end of follow-up，the HBV-related compensated liver cirrhosis group had significantly lower aminotransferase levels ［ALT： 31.00（19.00～47.50） U/L vs 40.00（27.00～57.00） U/L， Z=2.433， P<0.05； AST： 31.00（23.00～45.50） U/L vs 37.00（25.00～52.00） U/L， Z=1.963， P<0.05］， but significantly higher level of white blood cells （WBC） ［（4.02±1.56）×10⁹/L vs （3.59±1.24）×10⁹/L， t=2.272， P<0.05］， neutrophils ［（2.39±1.17）×10⁹/L vs （1.87±0.94）×10⁹/L， t=3.284， P<0.05］， and platelets ［（143.93±68.10）×10⁹/L vs （121.88±49.72）×10⁹/L， t=2.588， P<0.05］. A lower level of HBsAg （OR=0.997， 95%CI： 0.996　—　0.999， P<0.001） and previous treatment with NAs （OR=5.889， 95%CI： 2.195　—　17.330， P<0.001） were positive predictive factors for clinical cure， while liver cirrhosis （OR=0.177， 95%CI： 0.063　—　0.470， P<0.001） was a negative predictive factor for clinical cure. During follow-up， no patients experienced acute decompensation or progression to hepatocellular carcinoma， and the main adverse events included fever， fatigue， reductions in WBC and platelets， weight loss， alopecia， and thyroid dysfunction. In the subgroup analysis of HBV-related compensated liver cirrhosis， in both the treatment-naïve patients and the patients previously treated with NAs， there was a significant reduction in HBsAg level from baseline to week 36 of treatment ［treatment-naïve： 99.25 （5.87　—　1 212.35） IU/mL vs 403.47 （36.94　—　2 569.02） IU/mL， P<0.05； previously treated with NAs： 205.94 （14.00　—　737.80） IU/mL vs 427.03 （65.64　—　1 552.65） IU/mL， P<0.05］ and week 48 of treatment ［treatment-naïve： 85.45 （0.58　—　827.56） IU/mL vs 403.47 （36.94　—　2 569.02） IU/mL， P<0.05； previously treated with NAs： 45.28 （0.16　—　267.27） IU/mL vs 427.03 （65.64　—　1 552.65） IU/mL， P<0.05］. There were significant increases in the levels of aminotransferases during treatment， as well as significant reductions in the levels of WBC， neutrophils， platelets， and hemoglobin （all P<0.05）. ConclusionAlthough a finite course of PEG-IFN-α-2b therapy has achieved a relatively low rate of clinical cure in the treatment of HBV-related compensated liver cirrhosis， it can still significantly reduce the level of HBsAg， and this treatment regimen has good safety and tolerability， without accelerating disease progression.

Objective To establish and evaluate a mouse model of chronic obstructive pulmonary disease(COPD)induced by cigarette smoke(CS).Methods Forty BALB/c mice were divided randomly into a control group and a CS group.Mice in the CS group were subjected to passive smoking for 20 weeks and a COPD model was established.Morphological changes in the organs and lung,heart,liver,and kidney fibrosis were observed by hematoxylin-eosin(HE)and Masson staining.Lung,cardiac,and brain cognitive function were evaluated by pulmonary function testing,small-animal ultrasound,and Morris water maze trials.Tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-1β levels in lung and brain tissues were detected by ELISA.Liver and renal functions were measured by biochemical method.Results The alveolar septum was narrowed or broken in mice in the CS group,and the adjacent alveolar cavity was enlarged and fused,consistent with the pathological changes of COPD.Neuronal degeneration and necrosis were observed in the hippocampus,but there were no significant morphological changes in other organs.Masson staining showed no obvious fibrosis in the lung,heart,liver,or kidney in CS-group mice.The result of pulmonary function tests showed that the forced expiratory volume in 0.1 second/forced vital capacity(FEV 0.1/FVC)and dynamic compliance were significantly decreased in the CS group compared with the control group,while airway resistance was obviously increased.Cognitive impairment in mice in the CS group was confirmed in the Morris water maze trial.TNF-α,IL-6,and IL-1β levels in lung and brain tissues were higher in the CS group compared with the control group.There were no significant differences in cardiac,liver,and renal functions between the groups.Conclusions A mouse model of COPD can be established by CS exposure for 20 weeks.Lung histomorphology,lung function,brain cognitive function,and levels of inflammatory factors can be used as indicators to evaluate the success of the model.

Age-related macular degeneration(AMD)is one of the leading causes of blindness in the elderly.Wet AMD(nAMD)accounts for more than 90％of AMD-related vision loss.Pathologically,nAMD is defined by choroidal neovascu-larization(CNV)and chronic retinal inflammation driven by oxidative stress,complement activation,pro-inflammatory cy-tokines,and overexpression of vascular endothelial growth factor(VEGF).Yet anti-VEGF monotherapy often falls short.The nuclear factor kappa-B(NF-κB)signaling cascade,acting through both canonical and non-canonical pathways,or-chestrates the expression of genes governing immunity,inflammation,apoptosis,and angiogenesis.In nAMD,oxidative stress and complement fragments ignite NF-κB,unleashing a repertoire of pro-inflammatory and pro-angiogenic mediators that fuel CNV.Pharmacologic or genetic suppression of NF-κB dampens both inflammation and neovascularization,attenua-ting experimental CNV.Thus,dissecting the molecular machinery of NF-κB signaling in nAMD may uncover novel combina-tion strategies that enhance therapeutic efficacy and curb anti-VEGF resistance.

The inherent clinical uncertainties, substantial costs, and small patient cohorts of orphan drugs limit the applicability of randomized controlled trial (RCT)-based health technology assessments (HTAs) in guiding coverage criteria, sustainable financing models, and equitable reimbursement frameworks for medical financial assistance policies for rare diseases.The digital transformation in healthcare system leads to solutions to the challenges in designing the policy by using data-driven decision-making. This article summarizes the decision-making issues in policy design, discusses the current status and trends of digital transformation, and analyzes the important new opportunities for AI-driven policy design for medical financial assistance policies for rare diseases. Decision-making that is digital intelligence driven and using techniques such as big data analytics and real-world research methods will enhance targeting efficiency, improve the quality of financing, and realize the performance-based reimbursement in the medical financial assistance, providing significant value in facilitating the policy reform and development for rare diseases healthcare.

Objective:To investigate the changes of home blood pressure from weekdays to weekends and its influencing factors.Methods:This study was a national multicenter prospective registry study. Data came from the registry study on the “Action of controlling home blood pressure to target in ten thousand patients”. Hypertension patients receiving antihypertensive drugs in the above study were included, and the general clinical data of the enrolled patients were collected. Patients′ office and home blood pressure were measured at baseline, followed by home blood pressure measurements for 7 consecutive days, and blood pressure trends over a one-week period were analyzed. Multivariate linear stepwise regression was used to investigate the influencing factors of blood pressure change from weekdays to weekends, and subgroup analysis was conducted according to body mass index, alcohol consumption, fasting blood glucose ≥6.1 mmol/L or diabetes mellitus. Kappa consistency test was used to analyze the influence of removing weekend blood pressure data on home blood pressure monitoring results. Results:A total of 3 228 hypertensive patients aged (66.2±7.6) years were included, including 1 612 (49.9%) males. The weekly blood pressure changes of the study subjects showed a trend of gradually increasing during working days (Monday to Friday) and decreasing during weekends (Saturday to Sunday). The blood pressure on weekends was lower than that on weekdays, but the difference was not statistically significant ((128.2±13.7)/(79.7±8.7) mmHg vs. (128.3±12.9)/(79.8±8.3) mmHg, all P>0.05; 1 mmHg=0.133 kPa). The blood pressure on Sunday was significantly lower than that on Friday ((127.9±13.3)/(79.6±9.1) mmHg vs. (128.5±13.3)/(80.0±9.0) mmHg, all P<0.05). Subgroup analysis showed that hypertensive patients who were overweight and obese, drank alcohol, and had fasting blood glucose≥6.1 mmol/L or combined diabetes mellitus had a smaller decrease or increasing trend in home blood pressure from weekdays to weekends. Consistency test results showed that the mean blood pressure after removing the 2-day home blood pressure data on weekends was consistent with the mean blood pressure of one week ( Kappa=0.90). The mean blood pressure after removing only the blood pressure data of Sunday was slightly less consistent with the mean blood pressure of one week ( Kappa=0.88). Conclusions:The home blood pressure level of hypertensive patients receiving antihypertensive drugs showed a trend of gradually increasing during working days and decreasing at weekends. People with hypertension who were overweight and obese, drank alcohol, had high fasting blood sugar, or had combined diabetes mellitus, and their home blood pressure decreased less or increased from weekdays to weekends. The removal of 1-day Sunday blood pressure data but not 2-day weekend blood pressure data had impact on the one-week home blood pressure monitoring results.

Dental stem cells(DSCs),a distinct subset of mesenchymal stem cells(MSCs),are isola-ted from dental tissues,such as dental pulp,exfoliated deciduous teeth,periodontal ligament,and apical papilla.They have emerged as a promising source of stem cell therapy for tissue regeneration and autoim-mune disorders.The main types of DSCs include dental pulp stem cells(DPSCs),stem cells from hu-man exfoliated deciduous teeth(SHED),periodontal ligament stem cells(PDLSCs),and stem cells from apical papilla(SC AP).Each type exhibits distinct advantages:easy access via minimally invasive procedures,multi-lineage differentiation potential,and excellent ethical acceptability.DSCs have demon-strated outstanding clinical efficacy in oral and maxillofacial regeneration,and their long-term safety has been verified.In oral tissue regeneration,DSCs are highly effective in oral tissue regeneration for critical applications such as the restoration of dental pulp vitality and periodontal tissue repair.A defining advan-tage of DSCs lies in their ability to integrate with host tissues and promote physiological regeneration,which render them a better option for oral tissue regenerative therapies.Beyond oral applications,DSCs also exhibit promising potential in the treatment of systemic diseases,including type Ⅱ diabetes and au-toimmune diseases due to their immunomodulatory effects.Moreover,extracellular vesicles(EVs)de-rived from DSCs act as critical mediators for DSCs' paracrine functions.Possessing regulatory properties similar to their parental cells,EVs are extensively utilized in research targeting tissue repair,immuno-modulation,and regenerative therapy—offering a"cell-free"strategy to mitigate the limitations associated with cell-based therapies.Despite these advancements,standardizing large-scale manufacturing,maintai-ning strict quality control,and clarifying the molecular mechanisms underlying the interaction of DSCs and their EVs with recipient tissues remain major obstacles to the clinical translation of these treatments into broad clinical use.Addressing these barriers will be critical to enhancing their clinical applicability and therapeutic efficacy.In conclusion,DSCs and their EVs represent a transformative approach in re-generative medicine,and increasing clinical evidence supports their application in oral and systemic diseases.Continuous innovation remains essential to unlocking the widespread clinical potential of DSCs.

Objective To establish and evaluate a mouse model of chronic obstructive pulmonary disease(COPD)induced by cigarette smoke(CS).Methods Forty BALB/c mice were divided randomly into a control group and a CS group.Mice in the CS group were subjected to passive smoking for 20 weeks and a COPD model was established.Morphological changes in the organs and lung,heart,liver,and kidney fibrosis were observed by hematoxylin-eosin(HE)and Masson staining.Lung,cardiac,and brain cognitive function were evaluated by pulmonary function testing,small-animal ultrasound,and Morris water maze trials.Tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-1β levels in lung and brain tissues were detected by ELISA.Liver and renal functions were measured by biochemical method.Results The alveolar septum was narrowed or broken in mice in the CS group,and the adjacent alveolar cavity was enlarged and fused,consistent with the pathological changes of COPD.Neuronal degeneration and necrosis were observed in the hippocampus,but there were no significant morphological changes in other organs.Masson staining showed no obvious fibrosis in the lung,heart,liver,or kidney in CS-group mice.The result of pulmonary function tests showed that the forced expiratory volume in 0.1 second/forced vital capacity(FEV 0.1/FVC)and dynamic compliance were significantly decreased in the CS group compared with the control group,while airway resistance was obviously increased.Cognitive impairment in mice in the CS group was confirmed in the Morris water maze trial.TNF-α,IL-6,and IL-1β levels in lung and brain tissues were higher in the CS group compared with the control group.There were no significant differences in cardiac,liver,and renal functions between the groups.Conclusions A mouse model of COPD can be established by CS exposure for 20 weeks.Lung histomorphology,lung function,brain cognitive function,and levels of inflammatory factors can be used as indicators to evaluate the success of the model.