1.Distribution characteristics of pathogens and influencing factors analysis of infections within 90 days after liver transplantation
Huabin PENG ; Haofeng XIONG ; Fei HOU ; Shuang ZHAO ; Yizhi ZHANG ; Tingting CUI ; Zhiying HE ; Jingyi LIU ; Liying SUN
Organ Transplantation 2026;17(2):212-226
Objective To investigate the distribution characteristics of pathogens causing infections within 90 days after liver transplantation and the influencing factors of infection. Methods Clinical data of 176 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital Affiliated to Capital Medical University from September 2021 to August 2024 were retrospectively analyzed. Patients were divided into the infection group (n=124) and the non-infection group (n=52) based on whether they developed infection within 90 days after transplantation. The distribution characteristics of pathogens in infected patients were analyzed. Univariate and multivariate logistic regression analyses were used to explore the influencing factors of infection. Results Among the 176 liver transplant recipients, 124 cases developed 243 episodes of 518 bacterial, fungal, viral or mycoplasma infections within 90 days after transplantation, with an overall infection rate of 70.5% (124/176). The composition of pathogens was mainly Gram-negative bacteria (38.6%, 200/518), followed by Gram-positive bacteria (32.2%, 167/518) and viruses (15.4%, 80/518), and fungi accounted for 13.1% (68/518). Among Gram-negative bacteria, the main pathogen was Klebsiella pneumoniae (6.8%, 35/518), and among Gram-positive bacteria, the main pathogen was Enterococcus faecalis (8.5%, 44/518). Viruses included Epstein-Barr virus (3.7%, 19/518) and cytomegalovirus (3.7%, 19/518), and fungi were mainly Candida albicans (6.8%, 35/518). The most common infection site among the 243 episodes was pulmonary infection (42.0%, 102/243), followed by abdominal infection (22.6%, 55/243) and bloodstream infection (18.1%, 44/243). The infections mainly occurred within 2 weeks after transplantation (60.9%, 148/243). Multivariate logistic regression analysis indicated that preoperative infection within 2 weeks, a high preoperative model for end-stage liver disease (MELD) score, and preoperative sarcopenia were independent risk factors for infection within 90 days after liver transplantation (all odds ratio>1, P<0.05). After multivariate correction, the levels of CD4+T cells and CD8+T cells within 90 days after surgery were independently associated with the occurrence of infection. Low levels of CD4+T cells and CD8+T cells might be related to an increased risk of infection. Conclusions The infection rate after liver transplantation is high, and the pathogens are mainly Gram-negative bacteria. The lungs are the most common infection site. Preoperative MELD score, preoperative sarcopenia and preoperative infection within 2 weeks are independent risk factors for infection within 90 days after liver transplantation. Regular monitoring of immune indicators CD4+T cells and CD8+T cells levels after transplantation is helpful to reduce the occurrence of post-transplantation infection.
2.Association between socio ecological risk factors, physical activity developmental trajectory and depressive symptoms among junior and senior high school students
SUN Zhiying, LIU Zhonghui, LI Fengqin, WANG Xiaoyang, XU Ke, CUI Yushan, ZHANG Xianwei
Chinese Journal of School Health 2026;47(5):676-679
Objective:
To explore the relationship between socio ecological risk factors (SERF), physical activity (PA) developmental trajectories, and depressive symptoms among junior and senior high school students in Tianjin, in order to provide theoretical support for comprehensive interventions for adolescent depression.
Methods:
A longitudinal follow up design was adopted. In September 2022, a baseline survey was conducted using a stratified cluster random sampling method in two junior high schools and two senior high schools in Tianjin, collecting data on students basic information, SERF, PA, and depressive symptoms. Two follow up surveys were conducted in September 2023 and 2024, yielding 588 valid participants. Latent class growth analysis (LCGA) was used to identify PA developmental trajectory categories among junior and senior high school students. Logistic regression was applied to examine the associations between depressive symptoms and SERF as well as PA trajectories.
Results:
The detection rates of depressive symptoms among Tianjin junior and senior high school students over the three years were 26.53%, 20.24%, and 21.26 %, respectively. Depressive symptoms were positively correlated with SERF ( OR=1.04, 95%CI=1.03-1.05, P <0.05). The highest risks were observed in the individual dimension and family dimension ( OR =1.28, 1.21, both P <0.05). LCGA identified three PA trajectory groups:persistently low level (80.65%), persistently high level (4.58%), and slowly increasing group ( 14.77 %). Multivariate regression analysis showed that compared with the persistently low level PA, the slowly increasing PA significantly reduced the risk of depressive symptoms ( OR=0.44, 95%CI =0.20-0.88), while SERF still increased the risk of depressive symptoms ( OR=1.04, 95%CI =1.03-1.05) (both P <0.05).
Conclusion
SERF are risk factors for depression symptoms among junior and senior high school students, whereas slowly increasing PA development trajectory demonstrates a protective effect.
3.The Clinical and Genetics Characteristics of Oculopharyngodistal Myopathy
Jiaxi YU ; Zhihao QUAN ; Yilei ZHENG ; Jing AN ; Jing LIU ; Qingqing WANG ; Lingchao MENG ; Meng YU ; Zhiying XIE ; Jianwen DENG ; He LYU ; Wei ZHANG ; Yun YUAN ; Zhaoxia WANG
JOURNAL OF RARE DISEASES 2026;5(2):164-174
To analyze the clinical and genetic features of oculopharyngodistal myopathy (OPDM) patients and compare the phenotypic differences among various causative genes. A total of 65 genetically confirmed OPDM patients from 43 unrelated families, who were admitted to the Department of Neurology, Peking University First Hospital between January 2008 and December 2025, were retrospectively included.The general demographic data, clinical manifestations, laboratory/auxiliary examinations, muscle pathology, and genetic test results were systematically collected and analyzed. The clinical and pathological characteristics among different OPDM subtypes were compared. Among the 65 patients(39 male and 26 female), the mean age of onset was (31.20±10.43) years (range: 14 to 63 years). The initial symptom was predominantly distal limb weakness (67.44%), which gradually progressed to involve the extraocular muscles, pharyngeal muscles, facial muscles and proximal limb muscles. Serum creatine kinase levels were mildly to moderately elevated. Muscle pathological examinations revealed rimmed vacuoles and intranuclear inclusions (within muscle fibers). The mean duration from onset to diagnosis was (12.33±7.88) years (range: 1 to 32 years). All probands had negative results on conventional next-generation whole-exome sequencing; pathogenic variants were identified through third-generation long-read sequencing or OPDM-targeted repeat-primed polymerase chain reaction(RP-PCR). Among the 43 families, OPDM2 subtype was the most common genetic subtype ( OPDM2 was the predominant subtype in this study. All subtypes share similar age of onset and muscular pathological changes, yet exhibit distinct disease progression patterns. Future multicenter prospective cohort studies are warranted to further elucidate the clinical characteristics, pathogenetic mechanisms, and prognostic differences among OPDM subtypes.
4.Effects of Modified Baohe Pill (保和丸) Formula on Thoracic Drainage Volume,Chest Tube Duration, and Inflammatory Indices After Thoracoscopic Surgery for Lung Cancer:A Randomized Parallel-Controlled Study
Yi LIU ; Ling XU ; Zhiyi DONG ; Xuanting YE ; Yiyun HE ; Zhiying WANG ; Yabin GONG ; Lijing JIAO
Journal of Traditional Chinese Medicine 2026;67(20):2202-2209
ObjectiveTo evaluate the effects of modified Baohe Pill (保和丸) formula added to conventional pulmonary rehabilitation on thoracic drainage volume, chest tube duration, and peripheral blood inflammatory indices after video-assisted thoracoscopic surgery (VATS) for lung cancer. MethodsIn this randomized parallel-controlled study, 118 post-VATS patients were enrolled, with 59 cases in each group. The control group received conventional pulmonary rehabilitation, while the treatment group additionally received an oral decoction of modified Baohe Pill formula until chest tube removal and discharge. The primary outcome was total postoperative thoracic drainage volume, while the secondary outcomes included chest tube duration and inflammatory indices including the pre-treatment and post-treatment levels and relative changes in platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), aggregate index of systemic inflammation (AISI), and systemic inflammation response index (SIRI). Adverse events during the treatment period were recorded. ResultsThe total postoperative thoracic drainage volume was 850 (430, 1410) ml in the treatment group, lower than 1085 (660, 1720) ml in the control group (P<0.05). Total postoperative chest tube duration was 8 (6, 11) days in the treatment group, shorter than 10 (7, 11) days in the control group (P<0.05), whereas the interval from enrollment to removal did not differ significantly between groups (P>0.05). The postoperative NLR in the treatment group was lower than that in the control group, and the relative change in NLR was greater than that in the control group (P<0.05). No significant between-group differences were found in post-treatment levels or relative changes of the other five inflammatory indices (P>0.05). No treatment-related serious adverse events were reported in either group. ConclusionModified Baohe Pill formula plus conventional pulmonary rehabilitation has lower total postoperative thoracic drainage volume, shorter total postoperative chest tube duration, and lower NLR levels in lung cancer patients following VATS, while demonstrating a more favorable safety profile than conventional pulmonary rehabilitation alone.
5.Clinical application value of donor care units in the maintenance of donor organs
Wanjing GAO ; Jixiang LIAO ; Jianhui DONG ; Rong MA ; Ningzi SUN ; Shuting CHEN ; Xuyang LIU ; Zhao GAO ; Jihua WU ; Zhiying LEI ; Qingdong SU ; Rong PENG ; Ning WEN ; Haibin LI ; Xuyong SUN
Organ Transplantation 2026;17(6):987-995
Objective To explore the value and operational effectiveness of establishing a donor care unit (DCU). Methods A single-center retrospective cohort study design was adopted. The DCU of the Transplant Center of the Second Affiliated Hospital of Guangxi Medical University was officially put into use on August 1, 2023. As of April 30, 2024, 200 donors were divided into the DCU group (n=107) and the non-DCU group (n=93) based on the different donor maintenance sites. Baseline data of donors, organ maintenance management indicators, organ output and utilization were collected and analyzed; simultaneously, the perioperative effects and 1-year postoperative prognosis of 314 recipients undergoing kidney transplantation at the Transplant Medicine Institute of the Second Affiliated Hospital of Guangxi Medical University were tracked. Results Compared with the non-DCU group, the usage rate of vasoactive drugs in the DCU group was lower, the completeness rate of pathogen culture and the proportion of daytime organ acquisition surgeries were higher, the cold ischemia time of the liver was shorter, the professional maintenance time of donors was longer, but the total hospitalization cost of donors was higher (all P<0.05). The 24-hour urine volume of donors in the DCU group increased, the level of creatine kinase decreased, and electrolyte indicators such as procalcitonin, lactate, blood sodium and blood chloride improved (all P<0.05). The cardiac output rate of donors in the DCU group was higher than that of the non-DCU group (P<0.05). The perioperative indicators, 1-year postoperative survival rates and graft survival rates of kidney transplant recipients in both groups were similar, but the serum creatinine level of recipients in the DCU group was lower after 1 year (P<0.05). Conclusions The management and operation efficiency of the DCU are good. By monitoring and regulating the stable physiological state of donors, the quality of organs is guaranteed, thereby improving cardiac output rate and short-term function of the transplanted kidney. The total hospitalization cost of donors is higher, and its comprehensive benefits need to be studied. However, it provides preliminary evidence-based basis for the clinical application of the DCU.
6.Protective Effect of Tongluo Baoshen Prescription-containing Serum on Lipopolysaccharide-induced Podocyte Injury of Rats
Yongfang LIU ; Tiantian YIN ; Huiyang LIU ; Rui HUANG ; Zhiying FENG ; Li ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):139-148
ObjectiveTo observe the effects of Tongluo Baoshen prescription (TLBS)-containing serum on the rat podocyte injury induced by lipopolysaccharide (LPS) and explore the potential mechanisms. MethodsSD rats were used to prepare the blank serum, losartan potassium-containing serum, and low-, medium-, and high-dose TLBS-containing sera. Rat podocytes were cultured in vitro, and the effects of drug-containing sera on podocyte viability were detected by the cell counting kit-8 (CKK-8) method. The optimal intervention volume fraction of drug-containing sera and the optimal concentration of LPS for inducing the podocyte injury were determined. Rat podocytes were grouped as follows: normal control (NC, 10% blank serum), model control (MC, 20.00 mg·L-1 LPS+10% black serum), losartan potassium (LP, 20.00 mg·L-1 LPS+10% losartan potassium-containing serum), low-dose TLBS (TLBS-L, 20.00 mg·L-1 LPS+10% low-dose TLBS-containing serum), medium-dose TLBS (TLBS-M, 20.00 mg·L-1 LPS+10% medium-dose TLBS-containing serum), and high-dose TLBS (TLBS-H, 20.00 mg·L-1 LPS+10% high-dose TLBS-containing serum), and the interventions lasted for 48 h. The ultrastructure of podocytes was observed under a transmission electron microscope. The podocyte apoptosis was detected by the terminal deoxynucleoitidyl transferase mediated nick-end labeling (TUNEL) kit. Immunofluorescence was used to detect the expression of gasdermin D N-terminal fragment (GSDMD-NT) in podocytes. The mRNA and protein levels of G protein-coupled receptor family C group 5 member B (GPRC5B), nuclear factor-κB (NF-κB) p50, NF-κB p52, NF-κB p65, Rel B, c-Rel, NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate-specific protease-1 (Caspase-1), GSDMD-NT, interleukin (IL)-1β, IL-18, nephrin, integrin α3, and integrin β1 in podocytes were determined by real-time quaritiative polymerase chain reaction (Real-time PCR) and Western blot, respectively. ResultsCompared with the NC group, the MC group showed reduced podocyte protrusions and organelles, segmental missing of cell membranes, increased and swollen mitochondria, irregular nuclear membranes, light chromatin, increased TUNEL fluorescence-positive nuclei (P<0.01), obviously enhanced fluorescence intensity of GSDMD-NT, up-regulated mRNA and protein levels of GPRC5B, NF-κB p50, NF-κB p52, NF-κB p65, Rel B, c-Rel, NLRP3, caspase-1, GSDMD-NT, IL-1β, and IL-18 (P<0.01), and down-regulated mRNA and protein levels of nephrin, integrin α3, and integrin β1 (P<0.01) in podocytes. Compared with the MC group, the LP, TLBS-M, and TLBS-H groups showed improved ultrastructure of podocytes with increased protrusions, intact cell membranes, reduced organelles, and alleviated mitochondrial swelling, decreased TUNEL fluorescence-positive nuclei (P<0.01), weakened fluorescence intensity of GSDMD-NT, down-regulated mRNA and protein levels of GPRC5B, NF-κB p50, NF-κB p52, NF-κB p65, Rel B, c-Rel, NLRP3, caspase-1, GSDMD-NT, IL-1β, and IL-18 (P<0.01), and up-regulated mRNA and protein levels of nephrin, integrin α3, and integrin β1 (P<0.05, P<0.01). Moreover, the changes above were the most obvious in the TLBS-H group. ConclusionThe TLBS-containing serum can regulate the GPRC5B/NF-κB/NLRP3 pathway to inhibit pyroptosis, thereby ameliorating the podocyte injury induced by LPS.
7.Effect and mechanism of Jingangteng capsules in the treatment of non-alcoholic fatty liver disease based on gut microbiota and metabolomics
Shiyuan CHENG ; Yue XIONG ; Dandan ZHANG ; Jing LI ; Zhiying SUN ; Jiaying TIAN ; Li SHEN ; Yue SHEN ; Dan LIU ; Qiong WEI ; Xiaochuan YE
China Pharmacy 2025;36(11):1340-1347
OBJECTIVE To investigate the effect and mechanism of Jingangteng capsules in the treatment of non-alcoholic fatty liver disease (NAFLD). METHODS Thirty-two SD rats were randomly divided into normal group and modeling group. The modeling group was fed a high-fat diet to establish a NAFLD model. The successfully modeled rats were then randomly divided into model group, atorvastatin group[positive control, 2 mg/(kg·d)], and Jingangteng capsules low- and high-dose groups [0.63 and 2.52 mg/(kg·d)], with 6 rats in each group. The pathological changes of the liver were observed by hematoxylin-eosin staining and oil red O staining. Enzyme-linked immunosorbent assay was performed to determine the serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT), aspartate transaminase (AST), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-18. 16S rDNA amplicon sequencing and metabolomics techniques were applied to explore the effects of Jingangteng capsules on gut microbiota and metabolisms in NAFLD rats. Based on the E-mail:591146765@qq.com metabolomics results, Western blot analysis was performed to detect proteins related to the nuclear factor kappa-B (NF-κB)/NOD-like receptor family protein 3 (NLRP3) signaling pathway in the livers of NAFLD rats. RESULTS The experimental results showed that Jingangteng capsules could significantly reduce the serum levels of TG, TC, LDL-C, AST, ALT, TNF-α, IL-1β, IL-6, IL-18, while increased the level of HDL-C, and alleviated the hepatic cellular steatosis and inflammatory infiltration in NAFLD rats. They could regulate the gut microbiota disorders in NAFLD rats, significantly increased the relative abundance of Romboutsia and Oscillospira, and significantly decreased the relative abundance of Blautia (P<0.05). They also regulated metabolic disorders primarily by affecting secondary bile acid biosynthesis, fatty acid degradation, O-antigen nucleotide sugar biosynthesis, etc. Results of Western blot assay showed that they significantly reduced the phosphorylation levels of NF-κB p65 and NF-κB inhibitor α, and the protein expression levels of NLRP3, caspase-1 and ASC (P<0.05 or P<0.01). CONCLUSIONS Jingangteng capsules could improve inflammation, lipid accumulation and liver injury in NAFLD rats, regulate the disorders of gut microbiota and metabolisms, and inhibit NF-κB/NLRP3 signaling pathway. Their therapeutic effects against NAFLD are mediated through the inhibition of the NF-κB/NLRP3 signaling pathway.
8.Mechanism prediction and experimental verification of Maxing Shigan Decoction against influenza A virus infection based on UPLC-MS/MS and network pharmacology
Jiawang HUANG ; Jianing SHI ; Yang LIU ; Zhiying FENG ; Jingmin FU ; Siyu WANG ; Xuan JI ; Rong YU ; Ling LI
Digital Chinese Medicine 2025;8(4):532-542
Objective:
To investigate the chemical compositions of Maxing Shigan Decoction (麻杏石甘汤, MXSGD) and elucidate its anti-influenza A virus (IAV) mechanism from prediction to validation.
Methods:
Ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to analyze the chemical compositions of MXSGD. Network pharmacology theories were used to screen and identify shared targets of both the potential targets of active ingredients of MXSGD and IAV. A protein-protein interaction (PPI) network was then constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The binding stability between core bioactive compounds and key targets was validated by molecular docking and dynamic simulations. A total of 24 BALB/c mice were infected with IAV to build IAV mouse models. After successful modelling, the mouse models were randomly divided into model, MXSGD high-dose (2.8 g/kg), MXSGD low-dose (1.4 g/kg), and oseltamivir (20.14 mg/kg) groups, with an additional normal mice as control group (n = 6 per group). The treatments were administered by gavage daily between 8:00 a.m. and 10:00 a.m. for five consecutive days. Upon completion of the administration, the body weight ratio, lung index, protein content in the bronchoalveolar lavage fluid (BALF), and the levels of inflammatory factors including interleukin (IL)-6 and tumor necrosis factor (TNF)-α in mice were measured to preliminarily analyze the therapeutic efficacy of MXSGD against IAV infection. Furthermore, the expression levels of mechanistic target of rapamycin (mTOR), hypoxia inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF) proteins in the HIF-1 signaling pathway, which was enriched by network pharmacology, were detected by Western blot.
Results:
A total of 212 chemical components in MXSGD were identified by the UPLC-MS/MS method. These chemical components can be classified into 9 primary categories and 31 secondary categories. After intersecting the chemical component targets with IAV-related targets, a total of 567 potential MXSGD components targeting IAV were identified. The construction of PPI network and the results of both GO and KEGG enrichment analyses revealed that the anti-IAV effects of MXSGD were associated with multiple pathways, including apoptosis, TNF, HIF-1, and IL-17 signaling pathways. The results of molecular docking demonstrated that the binding energies between the core compound 1-methoxyphaseollin and key targets including HIF-1α, mTOR, and VEGF were all lower than – 5.0 kcal/mol. Furthermore, molecular dynamics simulations confirmed the structural stability of the resulting complexes. Animal experiments showed that compared with the normal controls, IAV-infected mice showed significantly reduced body weight ratio, markedly increased lung index, protein content in BALF, and the levels of inflammatory factors such as IL-6 and TNF-α (P < 0.01), thereby causing damage to the lung tissue; consequently, the expression levels of mTOR, HIF-1α, and VEGF proteins in the lung tissues of these mice were significantly elevated (P < 0.01). However, after MXSGD treatment, the mouse models presented a significant increase in body weight ratio, as well as marked decreases in lung index, protein content in BALF, and the levels of inflammatory factors including IL-6 and TNF-α (P < 0.01). Furthermore, the therapy alleviated IAV-induced injuries and significantly downregulated the expression levels of mTOR, HIF-1α, and VEGF proteins in lung tissues (P < 0.01 or P < 0.05).
Conclusion
MXSGD exerts anti-IAV effects through multi-component, multi-target, and multi-pathway synergism. Among them, 1-methoxyphaseollin is identified as a potential key component, which alleviates virus-induced lung injury and inflammatory response via the regulation of HIF-1 signaling pathway, providing experimental evidence for the clinical application of MXSGD.
9.Analysis of the impact of phase Ⅱ cardiac rehabilitation on the rehabilitation needs and physical activity of patients with coronary heart disease after interventional surgery
Ying ZHANG ; Xiwei ZHANG ; Jiahui WU ; Wenxian LIU ; Yan FENG ; Nan LI ; Yong SHAO ; Lixin ZHANG ; Yuan TIAN ; Zhiying LI ; Yin LI
Chongqing Medicine 2025;54(5):1080-1084
Objective To investigate the impact of phase Ⅱ cardiac rehabilitation on the rehabilitation needs and physical activity status of patients after coronary heart disease intervention.Methods A total of 90 patients with coronary heart disease who underwent percutaneous coronary intervention(PCI)in the Coronary Heart Disease Center of the hospital from August 2023 to August 2024 were selected as the research subjects.They were subjected to a 12-week standardized phase Ⅱ cardiac rehabilitation training.General data survey forms,cardiac rehabilitation scales,and the International Physical Activity Questionnaire were used for scale surveys to understand the patients' needs before and after rehabilitation and their weekly physical activity en-ergy expenditure.The cardiopulmonary exercise test gold standard,which reflects exercise capacity through three indicators-maximum oxygen uptake(VO2 max),anaerobic threshold(AT),and metabolic equivalents(MET),were used to compare the physical activity status before and after cardiac rehabilitation.Results Compared with before the implementation,after the implementation of cardiac rehabilitation,the autonomy score in-creased(21.36±1.85 vs.16.73±3.28),the process anxiety(12.60±3.87 vs.14.27±2.12)and outcome anxiety scores(2.31±1.76 vs.4.56±3.56)decreased,the level of low-intensity physical activity decreased[(2 711.62±1 487.09)min/week vs.(3 845.97±2 083.71)min/week],the levels of moderate-intensity[(1 314.67±783.54)min/week vs.(686.22±126.79)min/week],high-intensity[(1 861.33±798.27)min/week vs.(112.00±40.77)min/week],and total physical activity increased[(5 887.62±2 843.54)min/week vs.(4 644.19±2 287.16)min/week].The levels of VO2 max[(28.11±14.28)mL·min-1·kg-1 vs.(23.82±12.34)mL·min-1·kg-1],AT[(16.06±5.41)mL·min-1·kg-1 vs.(13.53±4.56)mL·min-1·kg-1],and MET[(6.89±1.59)mL·min-1·kg-1 vs.(5.78±1.21)mL·min-1·kg-1]all in-creased,with statistically significant differences(P<0.05).Conclusion Phase Ⅱ rehabilitation after PCI can effectively improve patients' physical activity levels.
10.A novel dual-targeting strategy of nanobody-driven protein corona modulation for glioma therapy.
Yupei ZHANG ; Shugang QIN ; Tingting SONG ; Zhiying HUANG ; Zekai LV ; Yang ZHAO ; Xiangyu JIAO ; Min SUN ; Yinghan ZHANG ; Guang XIE ; Yuting CHEN ; Xuli RUAN ; Ruyue LIU ; Haixing SHI ; Chunli YANG ; Siyu ZHAO ; Zhongshan HE ; Hai HUANG ; Xiangrong SONG
Acta Pharmaceutica Sinica B 2025;15(9):4917-4931
Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.


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