OBJECTIVE To evaluate the efficacy， safety， and cost-effectiveness of posaconazole for the prevention of invasive fungal infections （IFIs）. METHODS PubMed， Embase， CNKI， Wanfang data and other Chinese and English databases were searched， as well as the official websites of related health technology assessment （HTA）. Systematic review （SR）/meta-analysis， pharmacoeconomic studies， and HTA reports of posaconazole for the prevention of IFIs were collected. The retrieval time limit was from the establishment of the database to November 1， 2025. After screening the literature， extracting the data， and evaluating the quality of the literature， the results of the included studies were descriptively analyzed. RESULTS A total of 45 studies were included， involving 17 SR/meta-analyses， 26 pharmacoeconomic studies， 1 SR/meta-analysis combined with a pharmacoeconomic study， and 1 HTA report. In terms of effectiveness， posaconazole was significantly superior to other antifungal drugs （eg.， fluconazole， itraconazole） in reducing the incidence of IFIs， the incidence of invasive aspergillosis， all-cause mortality， and IFI-related mortality （ P ＜0.05）. In terms of safety， posaconazole was significantly superior to other antifungal drugs in the incidence of total adverse reactions （ P ＜0.05）， but there was no significant difference in the incidence of serious adverse reactions， the incidence of gastrointestinal advers e reactions， drug-induced liver injury， and the withdrawal rate due to adverse drug reactions （ P ＞0.05）. In terms of cost-effectiveness， most studies have shown that posaconazole possesses more cost-effectiveness advantages. CONCLUSIONS Posaconazole demonstrates favorable efficacy， safety， and cost-effectiveness in preventing IFIs.

OBJECTIVE To evaluate the efficacy and safety of cholesterol absorption inhibitors （ezetimibe and hybutimibe） combined with statins for the treatment of dyslipidemia. METHODS Randomized controlled trials （RCTs） about above-mentioned drug combination in patients with dyslipidemia were retrieved from CNKI，PubMed and other Chinese and English databases. The retrieval time limit was from the establishment of the database to October 2025. After screening the literature，extracting the data，and evaluating the quality of the literature，network meta-analysis was performed using R software. RESULTS A total of 36 RCTs were included. Results showed that in reducing low-density lipoprotein cholesterol （LDL-C） and total cholesterol （TC）， ezetimibe+statins and hybutimibe+statins were significantly superior to statins+placebo and placebo alone （ P ＜0.05）. The top two interventions according to surface under the cumulative ranking curve （SUCRA） rankings were both ezetimibe+statins and hybutimibe+statins. In terms of triglyceride （TG） lowering， both hybutimibe+statins and ezetimibe+statins were significantly better than statins alone， statins+placebo and placebo alone （ P ＜0.05）， with hybutimibe+statins and ezetimibe+statins ranking top two by SUCRA. For apolipoprotein B （ApoB） reduction， ezetimibe+statins was significantly superior to statins alone and placebo alone （ P ＜0.05）， and the top two SUCRA rankings were ezetim ibe+statins and statins+placebo. In terms of high-density lipoprotein cholesterol （HDL-C） increase， placebo was significantly better than statins alone， hybutimibe+statins， statins+placebo， and ezetimibe+statins （ P ＜0.05）， and the top two SUCRA rankings were placebo alone and statins alone.There was no statistically significant difference in the overall incidence of adverse reactions among the interventions （ P ＞0.05）. CONCLUSIONS Ezetimibe combined with statins shows significant advantages in reducing LDL-C， TC and ApoB， while the hybutimibe combined with statins may have potential advantages in lowering TG； both combination regimens have good safety.

Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.

High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Objective Based on clinical consultation practices,it systematically evaluates the outcomes of remote video consultation services,identifies key factors influencing these outcomes,and provides empirical evidence for optimizing telemedicine services.Methods It recruited 201 patients nationwide requiring video consultations,objectively recorded diagnostic outcomes,and analyzed influencing factors using hierarchical regression.Results Among the 201 participants,62(30.84％)achieved effective diagnosis and treatment,while 139(69.16％)did not meet expected outcomes.Hierarchical regression results revealed that disease category,physician title,availability of auxiliary diagnostic information,and presence of assisting personnel significantly impacted consultation outcomes(P＜0.05).Higher physician titles,richer auxiliary diagnostic information provided by patients,and involvement of assisting personnel correlated with better alignment of outcomes with expectations.Conclusion Significant variations in video consultation outcomes were observed,primarily influenced by assisting personnel,physician qualifications,auxiliary diagnostic information and disease category.It is suggested to introduce a large artificial intelligence model for pre-triage,set up standardized video consulting rooms in primary medical and health institutions and configure collaborative personnel,and build a regional patient information sharing platform,so as to improve patient satisfaction during treatment and promote the further development and optimization of video consultation.

Objective:To establish and optimize a novel method, focus forming assay (FFA), for quantitation of influenza A virus (FluA) and compare its application performance with traditional plague forming assay (PFA).Methods:The foci chromogenic effects of three peroxidase substrates in immunostaining were compared. The PFA and FFA methods were used to explore FluA incubation times and plaque morphology on 12-well plates, and to determine optimal incubation times and virus adsorption volumes for different FluA subtypes on 96-well plates. The correlation between FFA and PFA was evaluated, and the optimized FFA was applied to the in vitro antiviral efficacy analysis of Favipiravir and neutralization test against different subtypes of FluA. Results:TRUEBLUE substrate was identified as the optimal substrate for foci visualization. Compared with the PFA, the FFA showed improved sensitivity and reduced detection time in FluA titration, and good correlation was shown between the two methods′ results. By replacing the 96-well plate with the 12-well plate for FFA titration of different subtypes of FluA, the detection time was shortened, and the amount of serum samples used could be further reduced by optimizing the virus adsorption volume. The half-maximal effective concentration of favipiravir against influenza viruses assessed by the FFA and PFA methods showed no significant difference, and was consistent with the results obtained from quantitative PCR. Additionally, the focus reduction neutralization test and hemagglutination inhibition assays demonstrated strong correlation in determining antibody titers against FluA in serum neutralization assays.Conclusions:The improved FFA method developed here provides a more efficient experimental tool for FluA titration, antiviral drug screening and broad-spectrum vaccine evaluation.

Objective:To estimate the economic burden of 14 chronic diseases among middle-aged and elderly people in China.Methods:This cross-sectional study was based on longitudinal data from five waves (2011 to 2020) of the China Health and Retirement Longitudinal Study (CHARLS). Participants aged 45 and over who had been diagnosed with exactly one target chronic disease were included in the study. The 14 chronic diseases included: hypertension, dyslipidemia, diabetes or elevated blood glucose, malignant tumors, chronic pulmonary diseases, liver diseases, heart diseases, stroke, kidney diseases, digestive system diseases, emotional and mental diseases, memory-related diseases, arthritis or rheumatic diseases, and asthma. The economic burden of disease was measured in terms of both direct and indirect economic burden, with the results adjusted using a healthcare-specific Consumer Price Index (CPI). The direct economic burden included direct medical and non-medical burden. The human capital method was employed to calculate the indirect economic burden. A generalized linear mixed model (GLMM) was conducted to compare the differences in the economic burden between urban and rural areas, with provinces and prefecture-level cities set as random effects and residence (urban or rural areas) as fixed effects to control for the effects of geographic hierarchical structure. Gender, age and educational attainment were also included as covariates to control for confounding factors. The model′s robustness was assessed by comparing the significance of urban-rural differences before and after adding the covariates.Results:The median annual economic burden of the 14 chronic diseases among the middle-aged and elderly population in China ranged from 7 565 to 17 174 CNY, of which the direct economic burden ranged from 6 909 to 16 565 CNY, and the indirect burden ranged from 284 to 1 276 CNY. The direct economic burden was primarily driven by direct medical burden (83.67% to 95.01% of direct economic burden). Out-of-pocket expenses for outpatient medical burden ranged from 50% to 100%, while those for inpatient ranged from 36.30% to 61.29%. GLMM analysis revealed no statistically significant difference in the overall economic burden between urban and rural areas across diseases. However, the burden of inpatient medical burden for arthritis or rheumatism was higher in urban areas than in rural areas (5 338 vs. 3 898 CNY; LR=6.04, P=0.014). Similarly, the burden of self-treatment for hypertension was also higher in urban areas than in rural areas (324 vs. 238 CNY; LR=8.30, P=0.004). The outpatient non-medical burden for diabetes or elevated blood glucose (59 vs. 149 CNY; LR=5.99, P=0.014), stroke (0 vs. 307 CNY; LR=4.55, P=0.033), and digestive system diseases (45 vs. 107 CNY; LR=9.58, P=0.002) was lower in urban areas than rural. Conclusions:Chronic diseases cause heavy economic burden on middle-aged and elderly people in both urban and rural areas of China, with direct economic burden accounting for the majority of expenditure. The outpatient medical burden accounts for a higher proportion of out-of-pocket expenses than the inpatient.

Objective:To present an evaluation indicator system for access to cancer screening services.Methods:The evaluation indicator pool was constructed through a scoping review. The theoretical framework was constructed based on the multi-source indicators, and the qualitative expert consultation method was employed to form the initial version of the three-level evaluation indicator system. Delphi expert consultation method was conducted in two rounds to evaluate the relevance, importance, and availability of the proposed evaluation indicator system. The expert positive coefficient, authority coefficient, coordination degree of expert opinions, and concentration of expert opinions were subjected to analysis. Subsequently, the three-level evaluation indicator system for access to cancer screening services was adjusted and determined based on the boundary value method and the open opinions of experts. Finally, the combination weight method was employed to determine the weight.Results:The initial version of the indicator system comprised 3 primary (first-level) indicators, 11 secondary (second-level) indicators, and 46 tertiary (third-level) indicators. Delphi expert consultation was conducted for the initial version, and 17 experts ultimately completed it, exhibiting a positive coefficient of 100% and an authority coefficient of 0.87. In comparison to the initial round of consultation, Kendall's W coefficient ranges (0.15-0.43, all P<0.05) of relevance, importance, and availability scores for each tertiary indicator in the second round exhibited an improvement. The analysis of the importance dimension indicates that expert opinions are also more concentrated, as evidenced by an increase of 8.5% and 7.0% in the proportion of the tertiary indicators with an arithmetic mean above 8 and a full mark ratio above 0.5, respectively. The final evaluation indicator system comprises three primary indicators, with the weights of structure evaluation, process evaluation, and outcome evaluation being 0.338, 0.378, and 0.285, respectively. It also comprises 11 secondary indicators and 45 tertiary indicators. Conclusions:The evaluation indicator system developed in this article can be an effective evaluation tool for quantitative comparison of access to cancer screening services across different populations, cancer types, and before and after intervention. Furthermore, it is recommended that the system undergo continuous optimization concerning its application.