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.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

Objective: To explore the key factors affecting the selection and effectiveness of bladder management modalities in patients with spinal cord injury，so as to provide reference for the optimization of individualized bladder management strategies. Methods: The clinical and follow-up data of 78 patients with spinal cord injury treated in our hospital during Jan.1,2013 and Dec.31,2022 were retrospectively analyzed.The distribution of bladder management modalities among different grades of injuries was analyzed. Bowker symmetry test was used to evaluate the difference between bladder management modalities at discharge and at the end of follow-up. Multiple linear regression was used to explore the influencing factors of bladder management effects. Plotting Kaplan-Meier survival curves were adopted to calculate the median time of changes in bladder management. Results: At discharge，there were 9 cases of self-catheterization，19 cases of intermittent catheterization，22 cases of reflexive voiding，26 cases of long-term catheterization，and 2 cases using urinary collector.At the end of follow-up，there were 15 cases of self-catheterization，8 cases of intermittent catheterization，34 cases of reflexive voiding，14 cases of long-term catheterization，and 7 cases using urinary collector.There was a significant difference between the modalities of bladder management at discharge and at the end of follow-up (χ =21.43，P=0.018).Multiple linear regression showed a significant decrease of 8.60 in the total neurogenic bladder symptom score (NBSS) for grade D injuries compared with grade A injuries (P=0.026). The median time to bladder management change was 7.93 months (95%CI:5.44-9.44), with approximately 50% of patients experiencing a change in bladder management within 8 months after discharge. Conclusion: The modalities of bladder management changed significantly after discharge.The grade of injury was a key factor affecting the effectiveness of bladder management.Higher grade was associated with worse effectiveness of bladder management.

Objective: Previous observational studies have confirmed the correlation between gut microbiota and bladder cancer，but the causal relationship is still unclear.This study aimed to explore the causal relationship between them with Mendelian randomization. Methods: Genetic variation summary data of 211 gut microbiota and bladder cancer genome-wide association studies (GWAS) were obtained from the MiBioGen Consortium and Finngen database.Single nucleotide polymorphisms (SNPs) closely related to these studies were screened as instrumental variables.The causal relationship between gut microbiota and bladder cancer were analyzed with inverse variance weighting (IVW)，MR-Egger，weighted median，maximum likelihood，robust adjustment feature score and MR-PRESSO，with IVW as the primary analysis method.Additionally，sensitivity analysis was used to test the heterogeneity (Cochran Q) and horizontal pleiotropy (MR-Egger intercept term and global test from MR-PRESSO estimator) to ensure the robustness of the results. Results: The IVW results indicated that Lachnospiraceae UCG004 (OR：1.42)，Desulfovibrionales (Order) (OR：1.48)，Eubacterium ruminantium group (OR：1.33)，Olsenella (OR：1.24)，Ruminococcaceae UCG002 (OR：1.39)，Ruminococcaceae UCG005 (OR：1.42) and Ruminococcaceae UCG013 (OR：1.64) significantly increased the risk of bladder cancer.Conversely，Bacteroidetes (Phylum) (OR：0.61)，Eubacterium brachy group (OR：0.80)，Ruminococcaceae UCG004 (OR：0.73)，Rikenellaceae (Family) (OR：0.67)，Lachnospiraceae ND3007 group (OR：0.47), Adlercreutzia (OR：0.73) and an unknow genus (OR：0.75) were associated with a reduced risk of bladder cancer.Sensitivity analyses did not reveal any heterogeneity or horizontal pleiotropy. Conclusion: This study reveals the causal role of 14 gut microbiota in the pathogenesis of bladder cancer，among which Lachnospiraceae UCG004，Desulfovibrionales (Order)，Eubacterium ruminantium group，Olsenella，Ruminococcaceae UCG002，Ruminococcaceae UCG005 and Ruminococcaceae UCG013 are risk factors for bladder cancer，while Bacteroidetes (Phylum)，Eubacterium brachy group，Ruminococcaceae UCG004，Rikenellaceae (Family)，Lachnospiraceae ND3007 group，Adlercreutzia and an unknown genus are the protective factors.

The formation of portal vein thrombosis (PVT) is one of the complications of liver cirrhosis, which is easily overlooked but is not uncommon. With the deepening research on PVT in liver cirrhosis, evidence regarding the assessment of PVT formation, treatment effectiveness, and prognostic outcomes is continually being updated. This article summarizes recent studies on predicting the formation, anticoagulation efficacy, and survival models; analyzes and evaluates the rationality, standardization, and practicality of prediction models; and compares their strengths and weaknesses to provide a reference for clinicians in the individualized management and treatment of PVT in patients with liver cirrhosis.

Aim To investigate the protective effect of Shengmai Yin on myocardial ischemia/reperfusion in-jury(MI/RI)in vitro and in vivo and to unravel the underlying mechanism.Methods SD rats were divid-ed into the sham group,model group,and Shengmai Yin group(SM).Rat MI/RI model was established.Cardiac function,infarct area,pathological changes,cardiomyocyte apoptosis,macrophage infiltration,and serum cTnT and CK-MB levels were measured.The mRNA and protein expressions of Calpain-1 and Cal-pain-2 were assessed.The hypoxia/reoxygenation(H/R)model was constructed in H9c2 cells.The active ingredients of Shengmai Yin were screened using net-work pharmacology and verified by CCK-8.In the car-diomyocytes H/R model,Fluo-4 AM staining was used to detect the changes of Ca2+levels.Results Com-pared with model group,LVEF and LVFS of Shengmai Yin-treated rats increased,myocardial infarction area was reduced,while myocardial tissue injury was allevi-ated.Myocardial apoptosis rate and the number of macrophages were reduced.Similarly,cTnT and CK-MB levels decreased.In addition,the expression lev-els of Calpain-1 and Calpain-2 mRNA and protein de-creased in the SM treatment group.Under the H/R model,all the active ingredients of Shengmai decoction had protective effects on cardiomyocytes,and the treat-ment could reduce the level of Ca2+in cardiomyocytes.Conclusions Shengmai Yin has protective effects on MI/RI in rats.This effect may be related to the de-crease in Ca2+levels,as well as Calpain-1 and Calap-in-2 mRNA and protein expression.

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.

This paper aims to contribute to guaranteeing the stable development and enhancing the understanding of ecological agriculture of Chinese materia medica so that the national strategy and industrial demand can be better served. It first introduces current traditional Chinese medicine(TCM)policy and industrial development status from five aspects, including policy guarantee, theoretical support, technological innovation, standardization system, and brand influence. Then, the paper analyzes the development dilemma of TCM agriculture in production and quality increase and ecological environment protection. It also proposes the development goals of ecological agriculture of Chinese materia medica that meet the current industrial development demand, which are reducing chemical fertilizers, pesticides, and carbon emissions, improving quality, increasing efficiency, and protecting ecological environment. In addition, the new development goals are interpreted through case studies. Finally, this paper proposes four development strategies for ecological agriculture of Chinese materia medica: conducting research on the pattern and spatial and temporal variations of nationwide TCM production areas; studying the internal and external ecological memories of medicinal plant growth from the perspectives of genetic variations and environmental adaptation variations and elucidating their contributions to the formation of quality; carrying out selection and breeding of stress-resistant varieties for ecological agriculture of Chinese materia medica, the optimization of key technologies for soil improvement and restoration and green prevention and control against diseases and pests, and the improvement of quality; carrying out research on the quality assurance and value realization of ecological products made from TCM. This research can provide guidance for policy formulation, theoretical development of the discipline, and the enhancement of industrial technology for ecological agriculture of Chinese materia medica.
Agriculture/methods* ; China ; Drugs, Chinese Herbal ; Plants, Medicinal/chemistry* ; Ecosystem ; Materia Medica ; Medicine, Chinese Traditional

Buyang Huanwu Decoction(BYHWD), as one of the classic formulas in traditional Chinese medicine(TCM) for the treatment of cerebral ischemic stroke(CIS), has demonstrated definite effects in clinical practice. However, the material basis and mechanism of treatment have not been systematically elucidated. This study employed network pharmacology and molecular docking to analyze the potential targets and mechanisms of blood-and brain-penetrating active components of BYHWD in reducing cell apoptosis in CIS. Cell experiments were then carried out to validate the prediction results. In the experiments, five active components including hydroxysafflor yellow A( HSYA), tetramethylpyrazine( TMP), astragaloside Ⅳ( AS-Ⅳ), amygdalin( AMY), and paeoniflorin(PF) were selected to explore the pharmacological effects of BYHWD. HT22 cells were treated with BYHWD, and the cell counting kit-8(CCK-8) method was employed to examine the toxic and side effects of BYHWD. A cell model of oxygen-glucose deprivation/reoxygenation( OGD/R) was constructed, with apoptosis and pyroptosis as the main screening indicators. The levels of lactate dehydrogenase(LDH) and glutathione(GSH) were measured to assess the cell membrane integrity. Flow cytometry was employed to detect apoptosis, and the activities of caspase-3 and caspase-1 were measured to clarify the status of apoptosis and pyroptosis. ELISA was employed to determine the levels of interleukin(IL)-1β and IL-18 to confirm pyroptosis. HSYA and AMY were identified in this study as the active components regulating apoptosis and pyroptosis. TUNEL was employed to detect the apoptosis rate, and Western blot was employed to determine the expression levels of apoptosis-related proteins B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3, which confirmed that the anti-apoptotic effect of the combined component group was superior to that of the single component groups. The molecular docking results revealed strong binding affinity of HSYA and AMY with SDF-1α and CXCR4.AMD3100, a selective antagonist of CXCR4, was then used for intervention. The results of Western blot showed alterations in the expression levels of apoptosis-associated proteins, SDF-1α, and CXCR4. In conclusion, HSYA and AMY influence cellular apoptosis by modulating the SDF-1α/CXCR4 signaling cascade.
Drugs, Chinese Herbal/chemistry* ; Apoptosis/drug effects* ; Animals ; Neurons/cytology* ; Mice ; Molecular Docking Simulation ; Cell Line ; Glucose/metabolism* ; Humans ; Neuroprotective Agents/pharmacology*