ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Background: Malignant pleural effusion (MPE), a common complication of advanced cancers, is associated with poor prognosis and reduced quality of life. Although host–tumor interactions are known to drive MPE development, the associated immune dynamics during disease progression remain unclear. Using a Lewis lung carcinoma-induced MPE model in C57BL/6JNidfc mice, we systematically evaluated general parameters and immune cell changes at two-day intervals throughout disease progression. Results: The day of Lewis lung carcinoma cell injection into the pleural space was designated as day 0. By day 10 post-injection (p.i.), MPE-bearing mice exhibited ~ 10% body weight loss, marking the experimental endpoint. Pleural tumor mass and pleural effusion volume were minimal up to day 4 p.i. but increased sharply from day 6 onward.CD45⁺ immune cell counts rose over time, and days 6, 8, and 10 p.i. marked key stages of MPE progression. On day 6, B cells, T cells, and natural killer cells, but not macrophages and neutrophils, increased significantly compared to earlier timepoints. By day 8, all immune cell subsets except T cells exceeded day 6 levels, and at day 10, natural killer cell numbers declined while others continued to increase. Besides, the numbers of CD8⁺ T cells, Th1 cells, regulatory T cells, and M2 macrophages progressively increased from day 6 to 10. Based on these data, days 6 and 10 were defined as early and advanced MPE stages, respectively, with distinct immune phenotypes. In advanced MPE, CD8⁺ T cells displayed reduced IFN-γ, TNF-α, Granzyme B, Perforin, FasL, and Ki-67, but upregulated PD-1 and CTLA-4 relative to early stage. Similarly, Th1 cells showed decreased IFN-γ, TNF-α, and IL-2 production along with reduced Ki-67 expression. Advanced-stage M2 macrophages exhibited lower MHC-II levels and impaired phagocytosis, but higher PD-L1 and IL-10 production, while neutrophils showed reduced TNF-α release and phagocytic activity. Conclusions Our findings characterize the temporal immune dynamics associated with MPE progression in a mouse model, revealing a transition from an early immunostimulatory state to a late immunosuppressive state. This study enhances our understanding of MPE immunopathogenesis and provides a foundation for developing precise, stagespecific therapeutic strategies.

ObjectiveTo explore the effect of respiratory training based on core stabilization training on lumbar disc herniation. MethodsFrom January, 2023 to October, 2024, 96 patients with lumbar disc herniation admitted to the First Affiliated Hospital of Bengbu Medical University were divided into control group (n = 32), core group (n = 32) and respiratory group (n = 32). All the groups underwent conventional rehabilitation therapy, with core stabilization training in the core group and respiratory training combined with core stabilization training in the respiratory group, additionally, for four weeks. Before and after training, the scores of Visual Analogue Scale, Japanese Orthopaedic Association (JOA) and Oswestry Dysfunction Index (ODI) were compared, the average electromyographic value (AEMG) and root mean square (RMS) value of the multifidus and transversus abdominis were detected by surface electromyography (sEMG); and the thickness of the multifidus and transversus abdominis were measured by musculoskeletal ultrasonography bilaterally. ResultsThe intra-group effect (F > 597.796, P < 0.001), inter-group effect (F > 16.535, P < 0.001) and interaction effect (F > 49.622, P < 0.001) were significant in the scores of VAS, JOA and ODI; which were better in the respiratory group than in the control group and the core group (P < 0.05), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 7971.631, P < 0.001), inter-group effect (F > 177.760, P < 0.001) and interaction effect (F > 478.771, P < 0.001) were significant in the thickness of the transversus abdominis and multifidus; which were better in the respiratory group than in the control group and the core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 144303.007, P < 0.001), inter-group effect (F > 1495.458, P < 0.001) and interaction effect (F > 3121.361, P < 0.001) were significant in the RMS of the multifidus and transversus abdominis; which were better in the respiratory group than in the control group and the core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 1890.532, P < 0.001), inter-group effect (F > 607.132, P < 0.001) and interaction effect (F > 824.923, P < 0.001) were significant in the AEMG of the multifidus and transversus abdominis; which were better in the respiratory group than in the control group and core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). ConclusionCore training combined with respiratory training can more effectively reduce pain and improve dysfunction by enhancing the strength and control of the core muscles， thus improving the quality of life of patients with lumbar disc herniation.

ObjectiveTo investigate the anatomical features of three-dimensional （3D） reconstruction of the hepatic pedicle based on the Laennec’s capsule， as well as its application value in the development of extra-sheath dissection/occlusion clamp and precise hepatectomy. MethodsA retrospective analysis was performed for the abdominal contrast-enhanced CT data of 100 patients without anatomical abnormalities of the hepatic pedicle in The General Hospital of Western Theater Command from January 2021 to June 2024. The Hisense CAS system combined with the 3D U-net deep learning algorithm was used for 3D reconstruction of the hepatic pedicle at the level of Laennec’s capsule， and the hepatic pedicle was measured in terms of the length， outer diameter， and angle of the main trunk and branches. An extra-sheath hepatic pedicle dissection/occlusion clamp was developed based on the above measurements， and a total of 30 patients scheduled for right hemihepatectomy were enrolled and randomly divided into device group and control group， with 15 patients in each group. The two groups were compared in terms of hepatic pedicle handling time， time of operation， intraoperative blood loss， and the incidence rate of bile duct injury. The independent-samples t test was used for comparison of continuous data between two groups， and the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsThe results of 3D reconstruction revealed four variants in the main trunk branches of the hepatic pedicle， with type Ⅰ （left-right branching） accounting for 88% （88/100）， type Ⅱ （trifurcation type） accounting for 5% （5/100）， type Ⅲ （right anterior branching） accounting for 5% （5/100）， and type Ⅳ （special type） accounting for 2% （2/100）. The outer diameter of the main hepatic pedicle was 24.10±6.16 mm， the length of the left main branch was 20.59±6.38 mm， and the length of the right main branch was 21.99±7.98 mm. Compared with the control group， the device group had significantly shorter hepatic pedicle handling time （14.10±1.30 minutes vs 17.50±2.00 minutes， t=-5.620， P=0.001） and time of operation （217.00±28.28 minutes vs 241.87±19.49 minutes， t=-2.804， P=0.009）. The device group had a significantly lower incidence rate of bile duct injury than the control group （0 vs 20%， P=0.031）. Conclusion3D reconstruction based on the Laennec’s capsule can accurately display the anatomical variations of the hepatic pedicle. The extra-sheath hepatic pedicle dissection/occlusion clamp developed based on such data can optimize the process of hepatic pedicle management and improve surgical safety， and therefore， it holds promise for clinical application.

Objective To construct 5 machine-learning models and compare their performance in predicting the associations between pre-pregnancy socio-psycho-behavioral exposures of both spouses and preconception outcomes.Methods Based on Chongqing Preconception Reproductive Health and Birth Outcome Cohort of volunteers recruited from Chongqing Health Center for Women and Children during January 2019 and March 2022,5 447 couples were recruited and surveyed through interviewer-interview for the demographic and social-psychological-behavioral data of both spouses(221 variables).According to the inclusion and exclusion criteria,4 097 couples were finally included,and randomly assigned into a training set(n=2 867 spouses)and a validation set(n=1 230 spouses)at a ratio of 7∶3.Feature analysis and collinear screening were applied to select the potential exposure factors.In consideration of difficulty to carry out semen parameters analysis in primary healthcare institutions,feature Set 1 including sperm parameters and feature Set 2 excluding semen parameters were constructed by including or excluding sperm quality simultaneously in the training set and the validation set.Five algorithms,that is,Logistic Regression,Naive Bayes,Random Forest,Gradient Boosting Machine,and Support Vector Machine,were used to construct preconception outcome prediction models,and the parameters of each model were optimized using random search combined with grid search.The predictive performance of each model was compared using precision,recall,F1 score,area under the receiver operating characteristic curve(AUC),and calibration curve.The optimal model was then selected by comparing the changes in the predictive ability of the questionnaire data for fertility outcomes with or without semen parameters.Results There were 24 variables screened out in feature Set 1,and 16 variables in feature Set 2.In feature Set 1,the gradient boosting machine performed better,with a relatively higher AUC value(0.651)and better F1 score(0.61).The logistic regression model performed stably(AUC value=0.647)and was suitable as the reference model.The random forest(AUC value=0.641),Naive Bayes(AUC value=0.641),and support vector machine(AUC value=0.634)performed second-best.By utilizing the gradient boosting machine,comparable results were found between the predictions from feature sets with or without semen parameters,as in feature Set 1,the AUC value of its validation set was 0.651(95%CI:0.629～0.681),the prediction accuracy was 0.63,the recall rate was 0.65,and the average precision value F1 was 0.61;and in feature Set 2,the AUC value of its validation set was 0.649(95%CI:0.624～0.663),and both the calibration curves were close to the ideal curve.The prediction results indicated that in feature Set 1,the features highly negatively correlated with preconception outcomes were female age,male age,and no pregnancy within 1 year without contraception,while the features highly positively correlated with preconception outcomes were female pregnancy history,total sperm vitality,and use of contraceptive measures before enrollment.Conclusion Among the 5 machine-learning algorithms performed in this cohort data,the gradient boosting machine shows slightly better performance.There are 24 factors being associated with preconception outcomes in both spouses,and the performance of the simplified model excluding semen parameters is not significantly declined.It is feasible to use machine-learning methods to predict human preconception outcomes through social-psychological-behavioral questionnaires.

Polymer magnetic microspheres are a new type of composite functional materials,which have the advantages of stable structure,diverse modification methods,and magnetic response.These characteristics make polymer magnetic microspheres have the advantages of high sensitivity,high-specificity and fast response when detecting logo carriers or modified materials,and shows great application prospects in the fields of biomedicine and medical diagnosis.In this review,the basic properties of polymer magnetic microspheres were summarized,the research progresses of magnetic microspheres in the fields of biomedicine and medical diagnosis were emphatically introduced,and the improvement of preparation methods and development trends in the future were prospected.

Objective:To investigate the effect of FOXQ1 expression on chemoresistance in colorectal cancer and analyze its regulatory role in SIRT1 expression and p53 deacetylation under DNA damage response(DDR)condi-tions.Methods:qRT-PCR was used to detect FOXQ1 mRNA expression levels in SW620 cells and SW620 cells stimulated with cisplatin(CDDP).Lentiviral vectors were constructed for FOXQ1 overexpression and RNA interference.The cells were divided into three groups:FOXQ1 overexpression group(oe-FOXQ1),FOXQ1 RNA interference group(sh-FOXQ1),and a control group transfected with an empty vector(NC).The half-maximal inhibitory concentration(IC50)of CDDP in each group was determined using the CCK-8 assay.Apoptosis level and cell viability were assessed using the Annexin V-APC/7-ADD apoptosis detection kit and Calcein/PI staining.Western blot analysis was performed to evaluate the effect of FOXQ1 on SIRT1 expression and acetylated p53 levels.The SIRT1 pathway inhibitor(S)-Selisi-stat was introduced to observe changes in p53 acetylation levels.Results:Compared to normal colon tissues,FOXQ1 expression was significantly upregulated in SW620 cells(P＜0.05),and low-dose CDDP stimulation further en-hanced its expression(P＜0.05).After 24 hours of CDDP treatment,the IC50 values for the oe-FOXQ1,sh-FOXQ1,and NC groups were 58.3 μmol/L,36.4 μmol/L,and 43.7 μmol/L,respectively,with statistically significant differences among the groups(P＜0.05).Compared to the NC group,the oe-FOXQ1 group showed a decrease in late apoptotic cell count(P＜0.05),while the sh-FOXQ1 group exhibited an increase(P＜0.05).Cytotoxic fluorescence staining re-vealed that the proportion of cell death was lower in the oe-FOXQ1 group and higher in the sh-FOXQ1 group com-pared to the NC group(P＜0.05).Protein expression analysis showed that FOXQ1 and SIRT1 levels were higher in the oe-FOXQ1 group and lower in the sh-FOXQ1 group compared to the NC group(P＜0.05).FOXQ1 overexpression pro-moted p53 deacetylation,while the addition of the SIRT1 pathway inhibitor(S)-Selisistat restored p53 acetylation levels(P＜0.05).Conclusion:FOXQ1 promotes p53 deacetylation by upregulating SIRT1 expression,thereby inhibiting DDR-induced apoptosis.

Acute pancreatitis(AP)is a severe digestive system emergency characterized by high morbidity and mortality,with a complex pathogenesis involving multiple signaling pathways.Among them,the RhoA/ROCK signaling pathway plays a crucial role in the onset and progression of AP,influencing pancreatic inflammation,fibrosis,microcirculatory regulation,and interactions with other signaling pathways.Studies have shown that inhibiting the RhoA/ROCK signaling pathway can effectively alleviate AP severity,reduce inflammatory cytokine levels,and improve pancreatic microcirculation,offering new therapeutic insights and potential strategies for AP treatment.Therefore,this review systematically summarizes the structure and function of the RhoA/ROCK signaling pathway,explores its mechanistic role in AP progression,and further discusses its potential clinical applications.By integrating existing research findings,this paper aims to provide new perspectives on the role of this signaling pathway in AP and offer a theoretical foundation for future basic research and clinical applications.

Acute pancreatitis(AP)is a severe digestive system emergency characterized by high morbidity and mortality,with a complex pathogenesis involving multiple signaling pathways.Among them,the RhoA/ROCK signaling pathway plays a crucial role in the onset and progression of AP,influencing pancreatic inflammation,fibrosis,microcirculatory regulation,and interactions with other signaling pathways.Studies have shown that inhibiting the RhoA/ROCK signaling pathway can effectively alleviate AP severity,reduce inflammatory cytokine levels,and improve pancreatic microcirculation,offering new therapeutic insights and potential strategies for AP treatment.Therefore,this review systematically summarizes the structure and function of the RhoA/ROCK signaling pathway,explores its mechanistic role in AP progression,and further discusses its potential clinical applications.By integrating existing research findings,this paper aims to provide new perspectives on the role of this signaling pathway in AP and offer a theoretical foundation for future basic research and clinical applications.

Objective:To explore the effect of kidney-strengthening and blood stasis-eliminating formula on nutritional status and quality of life in patients with osteoporosis combined with hemodialysis.Methods:From January 2024 to January 2025,60 patients with liver and kidney yin deficiency and blood stasis obstruction were selected from the Pizhou City Traditional Chinese Medicine Hospital's Hemodialysis Center.60 patients were randomly divided into two groups,30 in each group.The matched group received general treatment plus paricalcitol,while the treatment group received the same treatment plus Yishen Zhuyu Fang(a traditional Chinese medicine formula for kidney and blood stasis).The treatment course lasted 12 weeks.Changes in TCM syndrome scores,the Modified Subjective Global Assessment(MQSGA),the Kidney and Life Quality(KDQOLTM-36)scale,lipid levels,and nutritional indicators were compared before and after treatment.Results:After treatment,the TCM syndrome scores in both groups decreased(P＜0.05),with a more pronounced decrease in the treatment group(P＜0.05).The KDQOLTM-36 score in the treatment group increased(P＜0.05),while the increase was not significant in the matched group(P＞0.05),indicating that the treatment group performed better than the matched group(P＜0.05).Both groups experienced a decrease in the MQSGA score(P＜0.05),although the difference was not statistically significant(P＞0.05),the treatment group showed a more noticeable decline.The TC,TG,LDL,and TG/HDL levels in the treatment group all decreased significantly,while HDL levels increased(P＜0.05).In contrast,the TC and HDL levels in the matched group did not change(P＞0.05),while the TG,LDL,and TG/HDL levels increased(P＜0.05).The treatment group performed significantly better than the matched group(P＜0.05).The TRF,Hb,and ALB levels in the treatment group increased(P＜0.05),while the increase was not significant in the matched group(P＞0.05).The total effective rate of the treatment group was 90％,higher than the matched group(23.3％)(P＜0.05).Conclusion:The formula of tonifying the kidney and removing stasis can improve the nutritional status and quality of life of patients with liver and kidney yin deficiency and blood stasis obstruction in hemodialysis combined with osteoporosis.