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 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.

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.

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 prognostic value of optic nerve sheath diameter(ONSD)measured by critical care ultrasound combined with serum biomarkers[S100 calcium-binding protein β(S100β)and neuron-specific enolase(NSE)]in patients with severe traumatic brain injury.Methods A total of 103 adult severe traumatic brain injury patients admitted to the intensive care unit of this hospital from A-pril 1,2023,to April 1,2024 were enrolled.All patients underwent invasive intracranial pressure monitoring after admission,alongside bedside critical care ultrasound measurement of ONSD at 3 mm behind the globe and serum biomarker testing.Baseline data and Glasgow outcome scale(GOS)scores at 90 days after dis-charge were recorded.Patients were divided into the survival and the non-survival groups based on GOS scores.Receiver operating characteristic(ROC)curve analysis and area under the curve(AUC)were used to evaluate the predictive performance of ONSD and serum biomarkers for poor prognosis in severe traumatic brain injury patients.Results Ninety-six patients were ultimately included,with 52(54.1％)in the survival group and 44(45.9％)in the non-survival group.Significant differences were observed in blood glucose,Glas-gow coma scale(GCS)score,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,ONSD,NSE,and S100β levels(P＜0.05)between the two groups.Multivariate analysis identified ONSD(OR=4.962,95％CI:3.473-6.254),NSE(OR=2.704,95％CI:1.987-3.033),S100β(OR=2.983,95％CI:1.843-4.571),and APACHE Ⅱ score(OR=3.726,95％CI:2.837-4.592)as independent predictors of mortality in severe traumatic brain injury patients(P＜0.05).The combination of ONSD,NSE,and S100β yielded an AUC of 0.840 for predicting poor prognosis,with a specificity of 88.3％and sensitivity of 98.6％.Conclusion ONSD and serum brain injury biomarkers(NSE,S100β)are associated with in-hospital prognosis in severe traumatic brain injury patients.Their combined detection can effectively predict a poor outcome.

Objective:To explore the effects of Xiaoyao Conger Decoction pretreatment on model rats of tinnitus with syndrome of liver-qi stagnation and spleen deficiency (TLSSD) and its preliminary mechanisms.Methods:The rats were divided into four groups: a blank group, a model group, a positive group, and Xiaoyao Conger high- and low-dosage groups, with 7 rats in each group according to random number table method. Except for the blank group, the TLSSD model was prepared by the composite etiological method in all groups of rats. The positive group received a gavage of carbamazepine at 15 mg/kg, while Xiaoyao Conger high- and low-dosage groups were given 30 g/kg and 15 g/kg of Xiaoyao Conger Decoction, respectively. The blank and model groups were administered an equal volume of saline once daily for 4 weeks. The frequency of conditioned avoidance response behaviors in rats was recorded before and at 2 and 4 weeks post-drug administration; TCM syndrome scores were documented before and after treatment; auditory brainstem response (ABR) thresholds were monitored at frequencies of 4, 12, 20, and 28 kHz; IL-1β mRNA expression in the inferior colliculus and cochlea was detected by RT-qPCR; and the levels of γ-aminobutyric acid (GABA) and glutamic acid (Glu) in hippocampal tissues were determined by LC-MS/MS.Results:The model group exhibited symptoms of liver depression, including irritability, yellow fur, and a dark red tongue, along with signs of spleen deficiency such as lethargy, decreased activity, and loose stools. Compared to the model group, rats in the Xiaoyao Conger high- and low-dosage groups demonstrated a reduction in conditioned avoidance response behaviors ( P<0.05 or P<0.01), a decrease in TCM syndrome scores ( P<0.05 or P<0.01), lower ABR thresholds at 12, 20, and 28 kHz ( P<0.01), reduced levels of IL-1β mRNA in the inferior colliculus and cochlea ( P<0.05 or P<0.01), and decreased hippocampal Glu levels ( P<0.01). Conclusion:The therapeutic effect of Xiaoyao Conger Decoction pretreatment on TLSSD rats may be related to its ability to improve the mood disorders and stress, reduce the neuroinflammatory response, regulate the CNS neurotransmitter balance, and correct the overexcitability of the auditory centre, etc.

Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

Objective To investigate the clinical value of peripheral eosinophil count(PEC)in predicting the outcome of diabetic nephropathy(DN).Methods A retrospective cohort trial was conducted on 220 DN patients identified by renal biopsy in Department of Nephrology of Second Affiliated Hospital from Army Medical University from March 2021 to March 2023.Clinical data,results of routine blood test and renal function were collected.X-tile bioinformatics software version 3.6.1 was used to determine the optimal cut-off value of PEC for predicting survival.Cox proportional hazards model and Kaplan-Meier survival analysis were applied to analyze the prognosis.Results The level of PEC in DN patients was positively correlated with the levels of serum creatinine(Scr)(r=0.245),blood urea nitrogen(BUN)(r=0.237)and blood uric acid(UA)(r=0.252),and negatively with estimated glomerular filtration rate(eGFR)(r=-0.236).According to the optimal PEC cut-off value,DN patients were divided into high-level group(＞0.29×109/L,n=41)and low-level group(≤0.29 × 109/L,n=179).The levels of Scr(P＜0.001),BUN(P=0.001)and UA(P=0.005)were significantly higher,while the eGFR(P＜0.001)was obviously lower in the high-level group than the low-level group.Multivariate Cox regression analysis showed that the high level of PEC was associated with poor prognosis of DN(HR=2.20,95％CI:1.05～4.60,P=0.036).Kaplan-Meier survival analysis demonstrated that the incidence of end-stage renal disease(ESRD)was notably higher in the high-level group than the low-level group(P=0.024).Conclusion PEC level of DN patients is closely associated with the progression and prognosis of DN,and the count is a potential biomarker for predicting the prognosis of DN.

Tumour metastasis is the primary cause of mortality in patients with tumours.Platelets are fragments of anucleated cells shed from the cytoplasm of mature megakaryocytes of the bone marrow，and involved in coagulation and the maintenance of vascular wall integrity.Recent studies have demonstrated that platelets participate in the host immune response by secreting granules containing a range of immunomodulatory and antimicrobial molecules，which are critical for tumour metastasis.In tumours，contact between platelets and tumour cells promotes platelet activation and aggregation.Activated platelets release a large number of reactive biomolecules that assist tumour cells in immune escape，migration，stationary adhesion and extravasation.Meanwhile，platelets accelerate tumour cell metastasis by inducing tumour epithelial mesenchymal transition，neoangiogenesis，metastatic ecological niche formation and other mechanisms.This article presents a review of the current state of research on the role of platelets in tumour metastasis，and offers insights into potential therapeutic avenues to enhance the survival of tumour patients.

To investigate the clinical significance of platelet-neutrophil ratio in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis(AAV),a total of 128 patients were recruited and retrospectively analyzed in our department from March 2015 to July 2023.Spearman correlation analysis indicated that there was negative correlation between the level of PNR and Birmingham vasculitis activity score(BVAS)in AAV patients(r=-0.268,P=0.002).According to the PNR optimal cutoff value(26.4)determinated by X-tile bioinformatics software version 3.6.1 for predicting the survival rate,AAV patients were divided into high level PNR(HPNR)group(≥26.4)(n=105)and low level PNR(LPNR)group(<26.4)(n=23).Kaplan-Meier survival analysis showed that the survival rate of HPNR group was significantly higher than that of LPNR group(P<0.001).The level of PNR was correlated with poor prognosis of kidney(OR=2.54,95%CI:1.1-5.88,P=0.029).In conclusion,the level of PNR is closely related to disease activity and prognosis of AAV,and it might be a potential biomarker for predicting the disease activity and predicting the prognosis.