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.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

ObjectiveTo investigate the protective effect and underlying mechanisms of the Bawei Chenxiang Wan （BCW） against myocardial ischemic injury. MethodsMyocardial ischemia in vivo was induced in rats by subcutaneous injection of isoproterenol （ISO）， and ex vivo ischemia was established by coronary artery ligation in isolated rat hearts. The effects of BCW， alcohol extracts and its polar extracts were evaluated on ST segment on electrocardiogram （ECG）， myocardial damage， hemodynamic parameters， and infarct size. The phosphorylation level of phosphatidylinositol 3-kinase （PI3K）， the expression of cuproptosis-related proteins， and the content of Cu²⁺ in myocardial tissue were detected. The regulatory relationship of the signaling pathway was verified using an oxygen-glucose deprivation （OGD） myocardial cell injury model， combined with PI3K agonists and inhibitors. ResultsBCW ameliorated ST-segment elevation on electrocardiograms（P＜0.01）， reduced serum levels of myocardial injury markers， improved hemodynamic parameters， upregulated PI3K phosphorylation（P＜0.01）， and decreased Cu²⁺ accumulation in rats with myocardial ischemia（P＜0.01）. Moreover， BCW reduced the myocardial infarct size. In the isolated rat heart model of ischemia， both the ethanol extract and various solvent fractions of BCW exerted protective effects and reduced Cu²⁺ content， among which the n-butanol fraction exhibited the most potent activity（P＜0.01）. Specifically， the n-butanol fraction upregulated PI3K phosphorylation（P＜0.01） and downregulated the expression of cuproptosis-related proteins， including ferredoxin reductase 1（FDX1）（P＜0.05）， lipoic acid synthetase（LIAS）， and dihydrolipoamide S-acetyltransferase（DLAT） oligomerization（P＜0.05）. In the OGD-induced cardiomyocyte injury model， treatment with a PI3K agonist inhibited DLAT oligomerization（P＜0.05）， whereas co-administration of a PI3K inhibitor attenuated the inhibitory effect of the n-butanol fraction on DLAT oligomer formation（P＜0.05）. ConclusionThe n-butanol fraction of BCW exerts a significant protective effect against myocardial ischemic injury， and its mechanism may involve activation of the PI3K and inhibition of cuproptosis.

ObjectiveTo investigate the protective effect and underlying mechanisms of the Bawei Chenxiang Wan （BCW） against myocardial ischemic injury. MethodsMyocardial ischemia in vivo was induced in rats by subcutaneous injection of isoproterenol （ISO）， and ex vivo ischemia was established by coronary artery ligation in isolated rat hearts. The effects of BCW， alcohol extracts and its polar extracts were evaluated on ST segment on electrocardiogram （ECG）， myocardial damage， hemodynamic parameters， and infarct size. The phosphorylation level of phosphatidylinositol 3-kinase （PI3K）， the expression of cuproptosis-related proteins， and the content of Cu²⁺ in myocardial tissue were detected. The regulatory relationship of the signaling pathway was verified using an oxygen-glucose deprivation （OGD） myocardial cell injury model， combined with PI3K agonists and inhibitors. ResultsBCW ameliorated ST-segment elevation on electrocardiograms（P＜0.01）， reduced serum levels of myocardial injury markers， improved hemodynamic parameters， upregulated PI3K phosphorylation（P＜0.01）， and decreased Cu²⁺ accumulation in rats with myocardial ischemia（P＜0.01）. Moreover， BCW reduced the myocardial infarct size. In the isolated rat heart model of ischemia， both the ethanol extract and various solvent fractions of BCW exerted protective effects and reduced Cu²⁺ content， among which the n-butanol fraction exhibited the most potent activity（P＜0.01）. Specifically， the n-butanol fraction upregulated PI3K phosphorylation（P＜0.01） and downregulated the expression of cuproptosis-related proteins， including ferredoxin reductase 1（FDX1）（P＜0.05）， lipoic acid synthetase（LIAS）， and dihydrolipoamide S-acetyltransferase（DLAT） oligomerization（P＜0.05）. In the OGD-induced cardiomyocyte injury model， treatment with a PI3K agonist inhibited DLAT oligomerization（P＜0.05）， whereas co-administration of a PI3K inhibitor attenuated the inhibitory effect of the n-butanol fraction on DLAT oligomer formation（P＜0.05）. ConclusionThe n-butanol fraction of BCW exerts a significant protective effect against myocardial ischemic injury， and its mechanism may involve activation of the PI3K and inhibition of cuproptosis.

ObjectiveTo observe the clinical efficacy of modified Xiangsha Liujunzi Decoction （香砂六君子汤， XLD） in the treatment of abemaciclib-related diarrhea of spleen-stomach deficiency type， and its regulatory effect on immune function in patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative （HR+/HER2-） breast cancer. MethodsA prospective， randomized， open-label， blinded-endpoint （PROBE） study was conducted. A total of 70 patients with advanced HR+/HER2- breast cancer and abemaciclib-related diarrhea were randomly divided into two groups， with 35 cases in each group. In addition to abemaciclib， the control group was treated with oral loperamide， while the trial group was treated with oral modified XLD. Both groups received treatment for 7 days as one course. The efficacy for diarrhea after treatment was compared between groups. Traditional Chinese medicine （TCM） syndrome score， Karnofsky performance status （KPS） score， inflammatory markers including interleukin-6 （IL-6） and C-reactive protein （CRP）， and immune function indicators including CD4⁺， CD8⁺， and CD4⁺/CD8⁺ ratio were compared between groups before and after treatment. Adverse events during the study were recorded， and safety was assessed. ResultsDuring the study， 1 case in the trial group and 2 cases in the control group， were lost to follow-up leaving 34 cases in the trial group and 33 cases in the control group for final analysis. The total effective rate of diarrhea in the trial group was 94.12% （32/34）， higher than 72.73% （24/33） in the control group （P＜0.05）. After treatment， both groups showed decreased TCM syndrome scores， increased KPS scores， increased CD4⁺， CD8⁺， and CD4⁺/CD8⁺ ratio， and decreased IL-6 and CRP levels （all P＜0.05）. Compared to the control group， the trial group had higher KPS scores， CD4⁺ levels， and CD4⁺/CD8⁺ ratios， and lower TCM syndrome scores and IL-6， CRP， and CD8⁺ levels （P＜0.05）. The incidence of adverse events in the trial group was 20.59% （7/34）， with an incidence of adverse drug reactions of 14.71% （5/34） after causality assessment； in the control group， the corresponding rates were 45.45% （15/33） and 39.39% （13/33）， respectively. The incidence of adverse events in the trial group was significantly lower than that in the control group （P＜0.05）. ConclusionModified XLD can effectively alleviate abemaciclib-related diarrhea in patients with advanced HR+/HER2- breast cancer of the spleen-stomach deficiency type， reduce levels of inflammatory cytokines， and regulate immune function， with a favorable safety profile.

Objective:To investigate the staging criteria of renal tuberculosis，and to analyze the diagnostic and therapeutic characteristics as well as prognostic outcomes at different stages.Methods:A retrospective analysis was conducted on the clinical data of 134 patients with renal tuberculosis who were admitted to the Second Hospital of Lanzhou University between January 2019 and December 2023.The study cohort included 62 males and 72 females，with a mean age of（46.63 ± 13.52）years and a mean body mass index（BMI）of（22.85 ± 3.73）kg/m 2. A total of 107 patients resided in rural areas. Sixty patients had a history of pulmonary tuberculosis. Tuberculous lesions were located in the left kidney in 72 cases and in the right kidney in 62 cases. The main presenting complaints included irritative lower urinary tract symptoms in 85 patients and systemic symptoms in 92 patients. Ureteral involvement was observed in 97 patients，bladder involvement in 32 patients，and genital involvement in 9 patients. Based on computed tomography（CT）findings，the number，extent，and degree of renal destruction caused by tuberculous lesions were comprehensively evaluated in axial，coronal，and sagittal planes. The primary staging criteria included lesion diameter（2 cm）and the proportion of renal volume involved by the lesion（one-third，one-half，and two-thirds）. Renal tuberculosis was classified into three stages and six subtypes：Stage Ⅰa，a solitary lesion with a diameter ≤ 2 cm；Stage Ⅰb，a solitary lesion >2 cm or multiple lesions confined within one-third of the renal volume；Stage Ⅱa，lesions involving more than one-third but confined within one-half of the renal volume；Stage Ⅱb，lesions involving more than one-half but confined within two-thirds of the renal volume；Stage Ⅲa，lesions involving more than two-thirds of the renal volume with a glomerular filtration rate（GFR）of the affected kidney <10 ml/min；and Stage Ⅲb，complete renal calcification，presenting as an “autonephrectomy”. Among the 134 patients included in this study，7 were classified as Stage Ⅰa，17 as Stage Ⅰb，20 as Stage Ⅱa，19 as Stage Ⅱb，62 as Stage Ⅲa，and 9 as Stage Ⅲb. The severity of hydronephrosis was graded as follows：mild，renal pelvic separation <2 cm；moderate，2-3 cm；and severe，>3 cm. Prior to treatment，the mean renal pelvic separation was（1.76 ± 0.92）cm in Stage Ⅰa，（1.69 ± 0.81）cm in Stage Ⅰb，and（1.10 ± 0.82）cm in Stage Ⅱa，corresponding to mild to moderate hydronephrosis. All 7 patients in Stage Ⅰa underwent ureteroscopic examination and double-J stent placement，combined with a 6-month short-course anti-tuberculosis regimen consisting of isoniazid，rifampicin，pyrazinamide，and ethambutol for 2 months（intensive phase），followed by isoniazid and rifampicin for 4 months（continuation phase）. Among the 17 patients in Stage Ⅰb，13 presented with hydronephrosis and underwent ureteroscopic examination and double-J stent placement in combination with 6 months of anti-tuberculosis therapy，while 4 patients with isolated renal tuberculosis received anti-tuberculosis therapy alone for 6 months.Of the 20 patients in Stage Ⅱa，4 with hydronephrosis underwent ureteroscopic examination and double-J stent placement plus 6 months of anti-tuberculosis therapy，whereas 16 underwent nephroureterectomy. All 19 patients in Stage Ⅱb underwent nephroureterectomy. Among the 62 patients in Stage Ⅲa，60 underwent nephroureterectomy，while 2 refused surgery and were treated with the 6-month short-course anti-tuberculosis regimen. Of the 9 patients in Stage Ⅲb，8 underwent nephroureterectomy；in 1 patient，surgery was not performed due to severe adhesions in the operative field，and the patient received the 6-month short-course anti-tuberculosis regimen instead. Follow-up assessments included clinical symptoms，erythrocyte sedimentation rate（ESR），serum creatinine，degree of renal pelvic separation，and imaging findings from urinary tract CT. Efficacy was evaluated according to the following criteria：Cure was defined as clinical stability with all of the following conditions：① improvement of systemic symptoms，including absence of flank pain，fever，and lower urinary tract irritative symptoms，with normalization of erythrocyte sedimentation rate（ESR）；② negative urine culture for Mycobacterium tuberculosis；and ③ complete calcification of renal lesions and/or no evidence of tuberculous lesions at other sites. Stable disease was defined as no change in the size or extent of renal tuberculosis lesions. Progressive disease was defined as enlargement or increase in the number of tuberculous lesions or involvement of additional sites. Results:Among the 7 patients in Stage Ⅰa，follow-up imaging after treatment showed a mean renal pelvic separation of（0.44 ± 0.56）cm，which was significantly reduced compared with baseline（ t = 3.909， P = 0.008）. Five patients achieved cure，1 remained stable，and 1 showed disease progression and subsequently underwent nephroureterectomy，resulting in postoperative cure. In Stage Ⅰb，among 13 patients with hydronephrosis，post-treatment imaging showed a mean renal pelvic separation of（0.8 ± 0.75）cm，a statistically significant improvement from baseline（ t = 5.633， P < 0.01）. Six patients were cured，4 remained stable，and 3 experienced disease progression and underwent nephroureterectomy. Of the 4 patients with isolated renal tuberculosis，2 were controlled，and 2 progressed and underwent nephroureterectomy. In Stage Ⅱa，among 4 patients with tuberculous hydronephrosis，post-treatment renal pelvic separation was（1.20±0.98）cm，with no significant difference from baseline（ t = -1.675， P = 0.193）；these patients underwent nephroureterectomy 1-2 years later. The remaining 16 patients without hydronephrosis underwent nephroureterectomy and were cured. All 19 patients in Stage Ⅱb underwent nephroureterectomy；17 were cured，and 2 developed ipsilateral perirenal fluid collections 3 months postoperatively，which resolved spontaneously with the standard 6-month anti-tuberculosis regimen. Among 62 patients in Stage Ⅲa，60 underwent nephroureterectomy. Of these，54 were cured；1 developed a urinary tract infection within 2 weeks postoperatively；3 showed contralateral renal disease progression at 3 months；and 1 developed ipsilateral perirenal fluid at 3 months，which resolved spontaneously with standard anti-tuberculosis therapy. One patient developed solitary kidney failure 7 months postoperatively and underwent ureteral stent placement，with disease remaining stable thereafter. Two patients refused surgery and received only anti-tuberculosis therapy；during follow-up，1 patient experienced disease progression and died of disseminated tuberculosis after 1 year，while the other developed contralateral renal involvement at 3 months and received standard 6-month therapy，with disease remaining stable. Among 9 patients in Stage Ⅲb，8 underwent nephroureterectomy and were cured. One patient，with severe adhesions precluding surgery，received anti-tuberculosis therapy alone，and disease remained stable over a 2-year follow-up. Conclusions:The CT-based staging system for renal tuberculosis proposed in this study（three stages and six subtypes）effectively reflects the severity of renal lesions and clearly delineates the clinical characteristics and prognostic outcomes at each stage. Stage Ⅰ patients treated with anti-tuberculosis drugs combined with double-J stent placement demonstrated favorable outcomes and high renal preservation rates. In contrast，Stages Ⅱ and Ⅲ patients showed poor responses to anti-tuberculosis therapy combined with drainage，with a higher risk of disease progression and relatively worse prognosis，highlighting the recommendation for early nephroureterectomy of the affected kidney.

Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.
Spermatogenesis/physiology* ; Animals ; Male ; Mice ; Epigenesis, Genetic ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Histones/metabolism* ; RNA Interference ; Testis/metabolism* ; Methylation ; Mice, Knockout ; Histone Demethylases

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura. This article presents the evidence and interpretation of the blood transfusion provisions for children with hematological diseases in the "Guideline for pediatric transfusion", aiming to assist in the understanding and implementing the blood transfusion section of this guideline.
Humans ; Child ; Hematologic Diseases/therapy* ; Blood Transfusion/standards* ; Practice Guidelines as Topic

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion for children undergoing hematopoietic stem cell transplantation is highly complex and challenging. This guideline provides recommendations on transfusion thresholds and the selection of blood components for these children. This article presents the evidence and interpretation of the transfusion provisions for children undergoing hematopoietic stem cell transplantation, with the aim of enhancing the understanding and implementation of the "Guideline for pediatric transfusion".
Humans ; Hematopoietic Stem Cell Transplantation ; Child ; Blood Transfusion/standards* ; Practice Guidelines as Topic