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.

Objective To compare the adverse reactions to pegasparaginase(PEG-ASP)and Erwiniaasparaginase(ASP)in the treat-ment of pediatric acute lymphoblastic leukemia(ALL)and to provide clinical guidance for treatment.Methods A total of 13 patients who were switched from PEG-ASP to Erwinia ASP due to allergic reactions during the induction phase of ALL treatment at the Depart-ment of Hematology and Oncology,Children's Hospital Affiliated of Zhengzhou University between February 2022 and February 2023 were selected as the case group.A control group of 26 patients treated with PEG-ASP and matched for sex at a ratio of 1∶2 was also selected.Pre-and post-treatment coagulation function,blood biochemistry,blood ammonia level,and gastrointestinal reactions were compared between the groups.Results There were no significant differences in AST,TB,UB,TC,TG,AMY,UN,Cr,APTT,and Fbg levels between the two groups,pre-and post-treatment.However,ALT,GGT,BB,and Glu levels were higher in the control group,whereas albumin was lower than in the case group(P<0.05).Both groups had an increased post-treatment blood ammonia level(P<0.05),with significantly a higher level observed in the case group than in the control group(P<0.001).No significant differences in adverse gastro-intestinal reactions were observed between the two groups.Conclusion Erwinia ASP and PEG-ASP affected liver function in pediatric ALL re-induction therapy with minimal effects on coagulation and weaker gastrointestinal reaction.Erwinia ASP significantly affected the blood ammonia level,and both treatments caused mild gastrointestinal reactions.Regular blood ammonia monitoring,post Erwinia ASP treatment,is recommended.

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

Liposomes serve as critical carriers for drugs and vaccines, with their biological effects influenced by their size. The microfluidic method, renowned for its precise control, reproducibility, and scalability, has been widely employed for liposome preparation. Although some studies have explored factors affecting liposomal size in microfluidic processes, most focus on small-sized liposomes, predominantly through experimental data analysis. However, the production of larger liposomes, which are equally significant, remains underexplored. In this work, we thoroughly investigate multiple variables influencing liposome size during microfluidic preparation and develop a machine learning (ML) model capable of accurately predicting liposomal size. Experimental validation was conducted using a staggered herringbone micromixer (SHM) chip. Our findings reveal that most investigated variables significantly influence liposomal size, often interrelating in complex ways. We evaluated the predictive performance of several widely-used ML algorithms, including ensemble methods, through cross-validation (CV) for both liposome size and polydispersity index (PDI). A standalone dataset was experimentally validated to assess the accuracy of the ML predictions, with results indicating that ensemble algorithms provided the most reliable predictions. Specifically, gradient boosting was selected for size prediction, while random forest was employed for PDI prediction. We successfully produced uniform large (600 nm) and small (100 nm) liposomes using the optimised experimental conditions derived from the ML models. In conclusion, this study presents a robust methodology that enables precise control over liposome size distribution, offering valuable insights for medicinal research applications.

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.

Objective:To summarize the clinical characteristics and key points of diagnosis and treatment in children with TCF3::HLF fusion gene-positive acute lymphoblastic leukemia (ALL).Methods:A case series study was conducted. Clinical data of 8 children diagnosed with TCF3::HLF positive ALL at the Hematology Center of Beijing Children′s Hospital, Capital Medical University and the Hematology Oncology Department of Henan Children′s Hospital between January 2019 and January 2024 were collected. Descriptive analysis was performed on their clinical features, laboratory findings, treatment regimens and prognosis.Results:The cohort included 8 children (3 males and 5 females) with the age of 5.5 (3.5, 7.0) years. Bone pain was the primary clinical manifestation in 4 cases, with multi-site skeletal involvement in 4 cases, hypercalcemia in 5 cases, and coagulation abnormalities in 6 cases. Immunophenotyping revealed common B-cell lineage with myeloid markers in 7 cases and common B-cell phenotype in 1 case. All 8 children were positive for the TCF3::HLF fusion gene. Regarding treatment, 1 case abandoned therapy after diagnosis, while the remaining 7 cases received chemotherapy following the Chinese Children′s Leukemia Group-ALL2018 high-risk protocol. Only 1 case achieved minimal residual disease (MRD) negativity by day 33 of induction therapy. Among the 3 cases with MRD negativity before consolidation therapy, 1 case achieved it via conventional chemotherapy, while 2 cases required additional agents (venetoclax or blinatumomab). One case failed to achieve MRD negativity after consolidation therapy and later discontinued treatment (survival periods: 7months).Of the 4 cases who achieved MRD negativity after consolidation, 2 cases received conventional chemotherapy and 2 cases achieved negativity following chimeric antigen receptor T-cell therapy (CART). All 4 cases underwent hematopoietic stem cell transplantation (HSCT). Two cases in the CART combined with HSCT group survived as of the last follow-up (survival periods: 22 and 13 months). In the conventional chemotherapy combined HSCT group, 1 case relapsed and died (survival: 38 months), and 1 case died from transplant complications (survival: 11 months). The other 2 cases achieved MRD negativity before consolidation therapy but did not receive regular subsequent chemotherapy. After MRD recurrence, they underwent CART therapy without HSCT and remained alive at the last follow-up (survival periods: 49 and 12 months).Conclusions:Children with TCF3::HLF positive ALL often present with bone destruction accompanied by hypercalcemia and coagulopathy at initial diagnosis. This subtype of ALL shows poor response to conventional chemotherapy regimens, characterized by low early remission rates and high relapse risk even after HSCT. Better therapeutic outcomes have been observed with small molecule targeted drugs, immunotherapy and CART therapy.

Objective:To investigate the dose characteristics of the Zeiss INTRABEAM system in air and water, providing dose reference for electronic brachytherapy.Methods:A Monte Carlo program was used to establish a three-dimensional model of a miniature X-ray source vacuum drift tube and a 4 cm spherical applicator. The process of electron beam bombardment on a gold target to generate X-rays was simulated, and parameters such as photon fluence spectrum, percentage depth dose, and half-value layer were calculated. Additionally, the radial dose uniformity in water was measured.Results:The average energy of X-rays at 3 cm in air was 20.8 keV, with a half-value layer of 0.08 mm Al. Under the influence of the applicator, the spectrum becomes hardened, with axial and radial average energies of 28.7 and 29.0 keV, respectively. In water, the percentage depth dose (PDD) curve follows an inverse cubic decay with depth, indicating strong dose concentration and rapid fall-off in near-field irradiation. The radial dose uniformity in water exceeded 99.5%.Conclusions:The INTRABEAM device emits low-energy X-rays characterized by shallow penetration depth, and concentrated dose delivery. Its highly uniform dose distribution ensures comprehensive coverage of the target area, making it particularly suitable for treating superficial tumors and for intraoperative radiotherapy at close range.

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.