To analyze the disease burden, temporal trends, and attributable risk factors of early-onset female breast cancer (EOBC) in China and globally from 1990 to 2021.

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.

Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

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.

Objective: To explore the longitudinal changes and related predictive factors of anxiety and intolerance of uncertainty (IU) among Chinese college students, so as to provide theoretical reference for promoting students mental health. Methods: Intolerance of Uncertainty Scale-short Form and the 7 item Generalized Anxiety Disorder Scale were administered among 5 683 students from 22 universities in Guangdong Province from September 10 to October 17, 2021 (T1, baseline survey), and from March 15 to April 22, 2023 (T2). Using paired sample t-test to analyze the changes in anxiety and IU among college students, a linear regression model was established to explore factors that can predict anxiety, IU and their changes during T1 and T2 periods. Results: During the T1 period, the average scores of anxiety and IU among college students were (3.26±3.46, 34.88±7.96), while during the T2 period, they were (4.41±4.16, 36.40±8.07). During the T2 period, the levels of anxiety and IU among college students were higher than those during the T1 period ( t=19.59, 13.67, P <0.01). The linear regression results showed that age ( B = -0.02 ), moderate ( B =-0.18) and poor ( B =-0.88) mental health status, as well as online browsing of Corona Virus Disease 2019 (COVID-19) epidemic (later called as epidemic) related information for >1-<3 hours ( B =-0.30) and ≥3 hours ( B =-0.22), all of which could negatively predict changes in anxiety during T1 to T2 periods. Living in rural areas ( B =0.11) could positively predict changes in anxiety during T1 to T2 periods ( P <0.05). Moderate ( B =-0.19) and poor ( B =-0.47) mental health status, browsing epidemic related information online for >1-<3 hours ( B =-0.32) and ≥3 hours ( B =-0.33), academic performance being moderately affected by the epidemic ( B =-0.10), and personal planning being moderately affected by the epidemic ( B =-0.13) and severely affected ( B =-0.22), all of which could negatively predict changes in IU during T1 to T2 periods ( P <0.05). Conclusions Levels of anxiety and intolerance of uncertainty increases significantly after epidemic. Mental health status of college students should need long term monitoring, and students with poor mental health should need special attention.

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 effect of pelvic rotation around coronal axis on the placement angle of acetabular prosthesis after total hip arthroplasty.Methods:According to Murary's definition, the angle between the acetabular axis and the sagittal plane was defined as the acetabular abduction angle, and the angle between the acetabular axis and the coronal plane as the anterior inclination angle. A simple mathematical solid geometry model was established by using the mathematical software GeoGebra to simulate the dynamic changes of the acetabular prosthesis when it rotated around the coronal axis, and the calculation formula of the dynamic changes of the anterior inclination and abduction angle of the acetabular prosthesis was derived. MatLab software was used to generate the function graph of pelvis forward inclination and abduction angle and deduce the motion of acetabular prosthesis.Results:The dynamic changes of acetabular tilt angle and abduction angle when the pelvis rotated around the coronal axis were functionally related to the anterior-posterior tilt of the pelvis in a nonlinear pattern. When the pelvis rotates around the coronary axis, the anterior inclination angle formula is α 1=arcsin (sinβ 1×cosα×cosθ+cosβ 1×sinα); When the acetabulum axis faces downwards the abduction angle formula is θ 1=arccot (cosβ 1×cotθ-sinβ 1×tanα/sinθ); When the acetabulum axis faces upwards the abduction angle formula is θ 1=π-abs[arccot (cosβ 1×cotθ-sinβ 1×tanα/sinθ)] withα being the initial acetabular forward angle, θ being the initial acetabular abduction angle, α 1 being the forward angle of the acetabular prosthesis after pelvic rotation, θ 1 being the external expansion angle of the acetabular prosthesis after pelvic rotation and β 1 being the rotation angle of the pelvis around the coronal axis. When the pelvis is tilted backward, the anterior inclination angle of the acetabular prosthesis increases first and then decreases, and the abduction angle continues to increase. When the pelvis is tilted forward, the abduction angle decreases first and then increases, and the anterior inclination angle continues to decrease to negative. Conclusion:When the initial anterior inclination angle and abduction angle of acetabular prosthesis change, the curve of anterior inclination and abduction angle change accordingly. The larger the initial anterior inclination angle is, the faster it reaches its peak value, and the larger the peak value is, the faster the abduction angle changes. The larger the initial abduction angle is, the slower the initial anterior inclination angle and the abduction angle change.

Objective To explore the effect of occupational skills relearning programme on hemiplegic arm motor function and ac-tivities of daily living(ADL)in stroke patients. Methods From February,2022 to August,2023,74 stroke patients in Guangdong Work Injury Rehabilitation Hospital were enrolled and randomly divided into control group(n=37)and experimental group(n=37).The control group received conventional rehabilitation training,and the experimental group received additional occupational skills relearning programme,for three weeks.They were assessed with Fugl-Meyer Assessment-Upper Extremi-ties(FMA-UE),Functional Test for the Hemiplegic Upper Extremity-Hong Kong(FTHUE-HK),Motor Activity Log(MAL)-amount of use(AOU)and MAL-quality of movement(QOM),modified Barthel Index(MBI),and Stroke Impact Scale(SIS)-Hand and SIS-ADL before and after treatment. Results The scores in all assessments improved significantly in both groups(|t|>3.597,P<0.05)after treatment,while the scores of FMA-UE,FTHUE-HK,MAL-AOU,MAL-QOM were higher in the experimental group than in the control group(|t|>2.352,P<0.05). Conclusion Occupational skills relearning programme could promote the recovery of hemiplegic arm motor and activity,and facilitate the use of the hemiplegic arm in daily life in stroke patients.

[Objective]To investigate the protective effect of Zhuangtongyin on the Middle Cerebral Artery Occlusion(MCAO)model by modulating ferroptosis through the Nrf2-SCL7A11/xCT-Gpx4 pathway and its underlying mechanism.[Methods]C57BL/6J mice were randomly divided into Sham operation group(Sham),model group(MCAO),low-dose Zhuangtongyin group(ZTY-L),high-dose Zhuangtongyin group(ZTY-H),with 5 mice in each group.The MCAO group was modelled by silica gel embolization,the middle cerebral artery of mice was embolized for 1h,then the silica gel was pulled out and reperfusion was performed after 72 h;and the other operations in the Sham group were the same as those in the MCAO group except that the thread plug was not inserted.The neural function of mice was evaluated by Zea-Longa method.TTC staining was used to evaluate the volume of cerebral infarction.The level of brain injury was evaluated by HE staining and Nissl staining.Prussian blue staining and the expression of iron transport-related carrier receptors TfR1 and DMT1 on mRNA level was detected by qPCR to evaluate the iron ion deposition level in mice brain.The expression of lipid peroxidation-related gene ACSL4 on mRNA level was detected by qPCR,and the content of 4-HNE was detected by ELISA kit to evaluate the lipid peroxidation level of mice brain.The expressions of ferroptosis marker PTGS2 mRNA level was detected by qPCR.The expressions of Nrf2,SCL7A11/xCT,Gpx4 in mice brain tissue were detected by Western-blot and immunofluorescence.[Results]Zhuangtongyin improved the nerve function of mice after MCAO(P＜0.05)and the cerebral infarction volume of mice(P＜0.05)and alleviate the pathological injury of cerebral cortex cells after MCAO operation.Zhuangtongyin attenuated the accumulation of trivalent iron ions in the brain tissue of mice following MCAO.Additionally,Zhuangtongyin downregulated the expression of TfR1 and DMT1 mRNA(P＜0.001),a transporter associated with cellular iron ion uptake,in the brains of post-MCAO mice.Furthermore,Zhuangtongyin reduced levels of lipid peroxidation product 4-HNE(P＜0.001)and suppressed ACSL4 mRNA expression in brain tissue post-MCAO(P＜0.001).Besides,Zhuangtongyin downregulated the expression of PTGS2 mRNA(P＜0.001),in the brains of post-MCAO mice.Zhuangtongyin increased the expression of nrf2 into the nucleus(P＜0.001),and increased the expression of xCT and Gpx4 in neurons after MCAO(P＜0.001).[Conclusion]Zhuangtongyin can enhance the nerve function and reduce cerebral infarction volume in MCAO/R mice,alleviate the pathological damage of cerebral cortex cells,and modulate the expression of key signaling molecules in the Nrf2-SCL7A11/xCT-Gpx4 pathway.Therefore,it is suggested that the mechanism by which Zhuangtongyin improves MCAO/R injury in mice may involve regulating ferroptosis through the Nrf2-SCL7A11/xCT-GPX4 pathway.

Objective To predict the potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest (RF) and maximum entropy (MaxEnt) models, so as to provide insights into O. hupensis surveillance and control in Yunnan Province. Methods The O. hupensis snail survey data in Yunnan Province from 2015 to 2016 were collected and converted into O. hupensis snail distribution site data. Data of 22 environmental variables in Yunnan Province were collected, including twelve climate variables (annual potential evapotranspiration, annual mean ground surface temperature, annual precipitation, annual mean air pressure, annual mean relative humidity, annual sunshine duration, annual mean air temperature, annual mean wind speed, ≥ 0 ℃ annual accumulated temperature, ≥ 10 ℃ annual accumulated temperature, aridity and index of moisture), eight geographical variables (normalized difference vegetation index, landform type, land use type, altitude, soil type, soil textureclay content, soil texture-sand content and soil texture-silt content) and two population and economic variables (gross domestic product and population). Variables were screened with Pearson correlation test and variance inflation factor (VIF) test. The RF and MaxEnt models and the ensemble model were created using the biomod2 package of the software R 4.2.1, and the potential distribution of O. hupensis snails after 2016 was predicted in Yunnan Province. The predictive effects of models were evaluated through cross-validation and independent tests, and the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS) and Kappa statistics were used for model evaluation. In addition, the importance of environmental variables was analyzed, the contribution of environmental variables output by the models with AUC values of > 0.950 and TSS values of > 0.850 were selected for normalization processing, and the importance percentage of environmental variables was obtained to analyze the importance of environmental variables. Results Data of 148 O. hupensis snail distribution sites and 15 environmental variables were included in training sets of RF and MaxEnt models, and both RF and MaxEnt models had high predictive performance, with both mean AUC values of > 0.900 and all mean TSS values and Kappa values of > 0.800, and significant differences in the AUC (t = 19.862, P < 0.05), TSS (t = 10.140, P < 0.05) and Kappa values (t = 10.237, P < 0.05) between two models. The AUC, TSS and Kappa values of the ensemble model were 0.996, 0.954 and 0.920, respectively. Independent data verification showed that the AUC, TSS and Kappa values of the RF model and the ensemble model were all 1, which still showed high performance in unknown data modeling, and the MaxEnt model showed poor performance, with TSS and Kappa values of 0 for 24%(24/100) of the modeling results. The modeling results of 79 RF models, 38 MaxEnt models and their ensemble models with AUC values of > 0.950 and TSS values of > 0.850 were included in the evaluation of importance of environmental variables. The importance of annual sunshine duration (SSD) was 32.989%, 37.847% and 46.315% in the RF model, the MaxEnt model and their ensemble model, while the importance of annual mean relative humidity (RHU) was 30.947%, 15.921% and 28.121%, respectively. Important environment variables were concentrated in modeling results of the RF model, dispersed in modeling results of the MaxEnt model, and most concentrated in modeling results of the ensemble model. The potential distribution of O. hupensis snails after 2016 was predicted to be relatively concentrated in Yunnan Province by the RF model and relatively large by the MaxEnt model, and the distribution of O. hupensis snails predicted by the ensemble model was mostly the joint distribution of O. hupensis snails predicted by RF and MaxEnt models. Conclusions Both RF and MaxEnt models are effective to predict the potential distribution of O. hupensis snails in Yunnan Province, which facilitates targeted O. hupensis snail control.