OBJECTIVE To provide direction and reference for the adjustment of the discount rate （DR） in China’s pharmacoeconomic guidelines. METHODS Search was conducted on the official websites of the International Society for Pharmacoeconomics and Outcomes Research， health technology assessment agencies in various countries/regions， as well as relevant websites of other upper-middle-income or high-income countries/regions. The recommended DR， adjustment trends， and setting rationales in pharmacoeconomic evaluation guidelines across different countries/regions were then summarized and compared. Based on theoretical derivation and literature analysis， the effects of different DR on the incremental cost-effectiveness ratio （ICER） were examined. RESULTS & CONCLUSIONS Among the 40 included guidelines， the base-case DR ranged from 1.5% to 5%， with 5% being the most common value； the range for sensitivity analysis was 0 to 12%. Thirty-six countries/regions applied the same DR to both costs and health outcomes， while in the Netherlands， Belgium， Poland and Czech Republic， DR for costs was higher than for health outcomes. In recent years， Korea， France and Ireland had lowered their DR in response to economic changes， whereas the Netherlands and Czech Republic had raised their DR for cost. The setting of the DR was primarily based on the public project investment interest rate or referred to recommendations from internationally authoritative institutions and other relevant guidelines. The direction and magnitude of the impact of different DR on the ICER largely depended on the distribution of costs and health outcomes between the intervention and reference measure. The setting and adjustment of DR were closely associated with the economic environment. Based on international experience, the DR in China can be lowered by 0.5% to 1.5%， and localized empirical research can be conducted using internationally common estimation methods.

Alzheimer's disease (AD) is regarded as a neurodegenerative disease, and it has been proposed that AD may be a systemic disease. Studies have reported associations between non-neurological diseases and AD. The correlations between AD pathology and systemic (non-neurological) pathological changes are intricate, and the mechanisms underlying these correlations and their causality are unclear. In this article, we review the association between AD and disorders of other systems. In addition, we summarize the possible mechanisms associated with AD and disorders of other systems, mainly from the perspective of AD pathology. Regarding the relationship between AD and systemic pathological changes, we aim to provide a new outlook on the early warning signs and treatment of AD, such as establishing a diagnostic and screening system based on more accessible peripheral samples.
Alzheimer Disease/therapy* ; Humans ; Brain/pathology*

Objective:To investigate the clinical manifestations, long-term survival, and prognosis of childhood T-cell acute lymphoblastic leukemia (T-ALL).Methods:Case summary.The clinical data of 43 T-ALL children who were diagnosed and treated in Children′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2010 to December 2021 were retrospectively analyzed.They were stratified for treatment according to the CCCG-ALL regimen, and the correlation of prognosis with the condition at initial diagnosis, early treatment response, and induced remission was analyzed.The Kaplan-Meier survival curve was used to analyze the survival rate, and the survival rates were compared between groups by the Log-rank test.The multivariate Cox regression model was used to analyze the impact of multiple factors on the long-term survival of children.Results:T-ALL patients accounted for 9.5% (43/451) of the total number of acute lymphoblastic leukemia patients admitted to the hospital at the same period.The median onset age of the 43 T-ALL patients was 7 years (1-13 years).Of the 43 patients included, 14 patients (32.6%) had concomitant mediastinal widening, 8 patients (18.6%) had concomitant giant mediastinal masses, and 4 patients (9.3%) had early precursor T-cell acute lymphoblastic leukemia (ETP-ALL) at initial diagnosis.These 43 children were treated according to the CCCG-ALL intermediate- and high-risk group regimen.Among them, 33 children (76.7%) achieved sustained remission, 5 children died, and 5 children had a relapse.As of September 30, 2024, the median follow-up time was 62 months (1-170 months), the 10-year event-free survival rate was (80.2±6.4)%, and the 10-year overall survival rate was (86.6±5.8)%.The median relapse time and 10-year cumulative relapse rate of the 5 relapsed children were 28 months (7-58 months) and (13.7±5.8)%, respectively.The relationship of prognosis with clinical characteristics at initial diagnosis and induced remission in 43 T-ALL children was analyzed.The results showed that patients aged ≥10 years, with a grade-1 non-central nervous system at initial diagnosis, ETP-ALL, abnormal chromosome number and structure, non-M1 status of bone marrow and minimal residual disease (MRD)≥ 1% on day 19 of induction treatment, and MRD ≥ 0.01% on day 46 to 55 of induction treatment had poorer long-term survival(all P<0.05).The multivariate analysis showed that age ≥10 years, ETP-ALL, and abnormal chromosome number and structure were risk factors of poor prognosis ( P=0.045, 0.030, 0.021). Conclusions:The CCCG-ALL regimen has a good overall therapeutic effect in children with T-ALL.Age ≥10 years, abnormal chromosome number and structure, ETP-ALL, grade-1 non-central nervous system at initial diagnosis, and early remission are risk factors of poor prognosis.Treatment after relapse in children with T-ALL is difficult.

Objective To explore the clinical characteristics and speech recognition capabilities characteristics of patients with different subtypes of sudden deafness.Methods 280 patients with unilateral sudden deafness who visited the First Affiliated Hospital of Wenzhou Medical University from January 2022 to October 2024 were randomly selected.They were grouped based on the type of pure-tone hearing threshold curve and the degree of hearing loss before treatment(with 76 cases of ascending type,91 cases of descending type and 113 cases of flat type).The general conditions,clinical incidences,maximum speech recognition rates,and efficacy data of each group were compared.Results When comparing clinical symptoms regarding disease course,degree of hearing loss,tinnitus,ear tightness,dizziness,etc.,and therapeutic effects,the ascending-type hearing loss was characterized by a mild degree,a high incidence of ear tightness,and a favorable prognosis.The flat-type has a short course of illness,a high incidence of tinnitus,and severe hearing loss.The descending-type presented with a long disease course and a poor prognosis.These differences were statistically significant(P＜0.05).In the comparison of average pure-tone hearing threshold value at speech frequencies and speech recognition rate,the average hearing threshold value of the flat-type at speech frequencies was higher than that of the other two types,and its speech recognition rate was lower,with statistical significance(P＜0.05).Conclusion Patients with different subtypes of sudden deafness exhibit distinct characteristics in terms of onset and prognosis.Quantifying the speech recognition rates of sudden deafness patients with different subtypes and degrees of hearing loss can serve as a reference for clinical diagnosis and treatment.This is of great significance for enhancing the accuracy of clinical diagnosis of sudden deafness,formulating personalized treatment plans,and improving patient prognosis.

Objective To explore the clinical characteristics and speech recognition capabilities characteristics of patients with different subtypes of sudden deafness.Methods 280 patients with unilateral sudden deafness who visited the First Affiliated Hospital of Wenzhou Medical University from January 2022 to October 2024 were randomly selected.They were grouped based on the type of pure-tone hearing threshold curve and the degree of hearing loss before treatment(with 76 cases of ascending type,91 cases of descending type and 113 cases of flat type).The general conditions,clinical incidences,maximum speech recognition rates,and efficacy data of each group were compared.Results When comparing clinical symptoms regarding disease course,degree of hearing loss,tinnitus,ear tightness,dizziness,etc.,and therapeutic effects,the ascending-type hearing loss was characterized by a mild degree,a high incidence of ear tightness,and a favorable prognosis.The flat-type has a short course of illness,a high incidence of tinnitus,and severe hearing loss.The descending-type presented with a long disease course and a poor prognosis.These differences were statistically significant(P＜0.05).In the comparison of average pure-tone hearing threshold value at speech frequencies and speech recognition rate,the average hearing threshold value of the flat-type at speech frequencies was higher than that of the other two types,and its speech recognition rate was lower,with statistical significance(P＜0.05).Conclusion Patients with different subtypes of sudden deafness exhibit distinct characteristics in terms of onset and prognosis.Quantifying the speech recognition rates of sudden deafness patients with different subtypes and degrees of hearing loss can serve as a reference for clinical diagnosis and treatment.This is of great significance for enhancing the accuracy of clinical diagnosis of sudden deafness,formulating personalized treatment plans,and improving patient prognosis.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Objective:To investigate the prevalence and severity of symptom burden among long-term survivors of oropharyngeal cancer after radiotherapy, to identify core symptom clusters, and to explore their correlation with quality of life.Methods:A previous retrospective study was conducted by the Cancer Hospital, Chinese Academy of Medical Sciences on patients with oropharyngeal cancer who underwent radiotherapy between January 2010 and December 2020. Patients who were still alive as of December 2023 were further followed and analyzed. From December 2023 to August 2024, symptom burden and quality of life were assessed using the Chinese version of the MD Anderson Symptom Inventory–Head and Neck Module (MDASI-HN) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Exploratory factor analysis (principal component analysis with Promax rotation) were used to identify symptom clusters. Spearman correlation analysis was performed to explore the relationship between total symptom cluster scores and standardized domain scores of quality of life. Multivariate linear regression analysis was further employed to determine the relationship between identified symptom clusters and overall quality of life.Results:A total of 273 patients were included, with a median follow-up duration of 6.2 years (range: 3.5-14.5 years) and a median age of 61 years (range: 27-88 years) at follow-up. The top 5 incidence rates of symptom reported by patients were mucus problems in the mouth or throat (147 cases, 53.8%), dental or gum issues (143 cases, 52.4%), xerostomia (140 cases, 51.3%), difficulty swallowing or chewing (95 cases, 34.8%), and taste disturbance (79 cases, 28.9%). Among them, xerostomia was the most serious symptom. The most frequently reported interference was impact on work (including household chores) (55 cases, 20.1%). Exploratory factor analysis identified 3 symptom clusters: fatigue-nausea cluster, eating-voice cluster, and xerostomia-sleep cluster, all of which were significantly correlated with lower overall quality of life of patients (all P<0.001). Conclusion:Long-term survivors of oropharyngeal cancer after radiotherapy experience substantial symptom burden. The fatigue-nausea, eating-voice, and xerostomia-sleep clusters are the core symptom clusters impacting quality of life.

Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

Objective To analyze the structural and phylogenetic characteristics of the mitochondrial genome from Bulinus globosus, so as to provide a theoretical basis for classification and identification of species within the Bulinus genus, and to provide insights into understanding of Bulinus-schistosomes interactions and the mechanisms of parasite transmission. Methods B. globosus samples were collected from the Ruya River basin in Zimbabwe. Mitochondrial DNA was extracted from B. globosus samples and the corresponding libraries were constructed for high-throughput sequencing on the Illumina NovaSeq 6000 platform. After raw sequencing data were subjected to quality control using the fastp software, genome assembly was performed using the A5-miseq and SPAdes tools, and genome annotation was conducted using the MITOS online server. Circular maps and sequence plots of the mitochondrial genome were generated using the CGView and OGDRAW software, and the protein conservation motifs and structures were analyzed using the TBtools software. Base composition and codon usage bias were analyzed and visualized using the software MEGA X and the ggplot2 package in the R software. In addition, a phylogenetic tree was created in the software MEGA X after sequence alignment with the software MAFFT 7, and visualized using the software iTOL. Results The mitochondrial genome of B. globosus was a 13 730 bp double-stranded circular molecule, containing 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 13 protein-coding genes, with a marked AT preference. The mitochondrial genome composition of B. globosus was similar to that of other species within the Bulinus genus. Phylogenetic analysis revealed that the complete mitochondrial genome sequence of B. globosus was clustered with B. truncatus, B. nasutus, and B. ugandae into the same evolutionary clade, and gene superfamily analysis showed that the metabolism-related proteins of B. globosus were highly conserved, notably the cytochrome c oxidase family, which showed a significant consistency. Conclusions This is the first whole mitochondrial genome sequencing to decode the compositional features of the mitochondrial genome of B. globosus from Zimbabwe and its evolutionary relationship within the Bulinus genus, which provides important insights for further understanding of the phylogeny and mitochondrial genome characteristics of the Bulinus genus.

Objective:To explore predictive value of pericoronary fat attenuation index(FAI)of the assessment of computed tomography(CT)for coronary restenosis post the surgery of percutaneous coronary intervention(PCI)in elderly patients with coronary heart disease(CHD).Methods:A total of 100 elderly patients with CHD who admitted to Harbin 242 Hospital and underwent PCI from August 2021 to August 2024 were prospectively selected,and they were divided into stenosis group(46 cases)and non-stenosis group(54 cases)based on whether occurred coronary artery restenosis after the surgery.Multivariate logistic regression was used to analyze the influence factors of occurring restenosis in elderly patients with CHD after PCI surgery,and the receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of FAI for restenosis post PCI surgery in patients with CHD.Results:The differences in lipoprotein a,fibrinogen(FIB),total bilirubin(TBIL),total cholesterol(TC),triglyceride(TG),Coronary artery Lesion Complexity Scoring System(SYNTAX)score and FAI were significant between the stenosis group and the non-stenosis group,and the differences were all statistically significant(t=11.819,27.088,38.363,2.632,4.106,7.773,3.231,P<0.05).There were no statistically significant difference in gender,age,body mass index(BMI),blood pressure,basically medical history,and the diameter of implanted stents between the two groups(P>0.05).Multivariate logistic regression analysis showed that lipoprotein a FIB TBIL,TC,TG,SYNTAX score,and FAI index were all influence factors for restenosis post PCI surgery in patients with CHD[OR=4.578(95%CI:2.645～7.932),3.850(95%CI:2.048～7.237),0.145(95%CI:0.052～0.405),6.133(95%CI:1.382～27.219),0.019(95%CI:0.002～0.158),1.264(95%CI:1.150～1.389),1.062(95%CI:1.024～1.102),P<0.05].The ROC curve analysis showed that the area under curve(AUC)value of the ROC curve of the FAI index was 0.760(95%CI:0.666～0.854)in predicting restenosis post PCI surgery,and the sensitivity,specificity,the maximum Youden index and the best cut-off value of that were respectively 89.1%,59.3%,0.484,-79.79,P<0.001.Conclusion:FAI has significant value in predicting restenosis post PCI surgery in elderly patients with CHD,and it can be used as basis of assessing clinical risk.