1.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.
2.Effect of behavior activation therapy on subthreshold depression and quality of life in patients with diabetes foot amputation
Dianju HE ; Qianyun LI ; Xuli SHANG ; Xingju YANG
Chinese Journal of Practical Nursing 2025;41(24):1858-1865
Objective:To explore the effect of behavioral activation therapy on subthreshold depression and quality of life in patients with diabetes foot amputation, and to provide reference for clinical psychotherapy and quality of life improvement in patients with diabetes foot amputation.Methods:A randomized controlled trial was conducted to select 50 patients with diabetes foot amputation from September to December 2023 in the People′s Hospital Affiliated to Shandong First Medical University by convenient sampling. The participants were divided into an control group and a observation group, with 25 cases in each group, using a random number table method. The patients in the control group received routine nursing care of diabetes feet, and the patients in the observation group were given behavior activation therapy on the basis of the control group. The Centre for Epidomiological Studies Depression Scale (CES-D), Behavioral Activation for Depression Scale-Short Form (BADS-SF), and Short Form Health Measure (SF-12) were used to assess patients′ subthreshold depression, behavior, and quality of life before the intervention, at the end of the intervention, and 3 months after the intervention.Results:The final number of patients who completed the study in the control group and observation group were 23 and 24, respectively. There were 11 males and 12 females in the control group, with an age of (69.70 ± 7.01) years. There were 12 males and 12 females in the observation group, with an age of (69.17 ± 6.83) years. At the end of the intervention and 3 months after the intervention, the CES-D scores of the observation group were (21.13 ± 2.19) and (18.83 ± 1.86) points, respectively, which were significantly lower than those of the control group (25.70 ± 1.72) and (25.91 ± 1.65) points, and the differences were statistically significant ( t=-7.93, -13.80, both P<0.05). At the end of the intervention and 3 months after the intervention, the BADS-SF behavioral activation dimension scores in the observation group were (17.67 ± 2.41) and (18.50 ± 2.19) points, respectively, higher than the control group's (11.83 ± 1.78) and (11.57 ± 2.02) points, and the differences were statistically significant ( t=31.65, 34.45, both P<0.05). The behavioral avoidance dimension scores were (9.48 ± 1.50) and (9.65 ± 1.99) points, respectively, lower than the control group's (10.75 ± 1.42) and (11.88 ± 1.57) points, and the differences were statistically significant ( t=6.53, 13.17, both P<0.05). Three months after the intervention, the total score of SF-12 in the observation group was (65.96 ± 2.94) points, and the psychological dimension score was (37.50 ± 4.14) points, both of which were higher than those in the control group (60.30 ± 2.42) and (30.13± 5.15) points, and the differences were statistically significant ( t=51.54, 5.42, both P<0.05). There were statistically significant differences in time, between groups, and interaction effects in CES-D score, scores of two dimensions of BADS-SF and SF-12 total score ( F values were 10.04-190.71). Conclusions:Behavioral activation therapy can improve the symptoms of subthreshold depression in patients with diabetes foot amputation, enhance their behavioral activation level, and improve the quality of life to a certain extent.
3.Effect of behavior activation therapy on subthreshold depression and quality of life in patients with diabetes foot amputation
Dianju HE ; Qianyun LI ; Xuli SHANG ; Xingju YANG
Chinese Journal of Practical Nursing 2025;41(24):1858-1865
Objective:To explore the effect of behavioral activation therapy on subthreshold depression and quality of life in patients with diabetes foot amputation, and to provide reference for clinical psychotherapy and quality of life improvement in patients with diabetes foot amputation.Methods:A randomized controlled trial was conducted to select 50 patients with diabetes foot amputation from September to December 2023 in the People′s Hospital Affiliated to Shandong First Medical University by convenient sampling. The participants were divided into an control group and a observation group, with 25 cases in each group, using a random number table method. The patients in the control group received routine nursing care of diabetes feet, and the patients in the observation group were given behavior activation therapy on the basis of the control group. The Centre for Epidomiological Studies Depression Scale (CES-D), Behavioral Activation for Depression Scale-Short Form (BADS-SF), and Short Form Health Measure (SF-12) were used to assess patients′ subthreshold depression, behavior, and quality of life before the intervention, at the end of the intervention, and 3 months after the intervention.Results:The final number of patients who completed the study in the control group and observation group were 23 and 24, respectively. There were 11 males and 12 females in the control group, with an age of (69.70 ± 7.01) years. There were 12 males and 12 females in the observation group, with an age of (69.17 ± 6.83) years. At the end of the intervention and 3 months after the intervention, the CES-D scores of the observation group were (21.13 ± 2.19) and (18.83 ± 1.86) points, respectively, which were significantly lower than those of the control group (25.70 ± 1.72) and (25.91 ± 1.65) points, and the differences were statistically significant ( t=-7.93, -13.80, both P<0.05). At the end of the intervention and 3 months after the intervention, the BADS-SF behavioral activation dimension scores in the observation group were (17.67 ± 2.41) and (18.50 ± 2.19) points, respectively, higher than the control group's (11.83 ± 1.78) and (11.57 ± 2.02) points, and the differences were statistically significant ( t=31.65, 34.45, both P<0.05). The behavioral avoidance dimension scores were (9.48 ± 1.50) and (9.65 ± 1.99) points, respectively, lower than the control group's (10.75 ± 1.42) and (11.88 ± 1.57) points, and the differences were statistically significant ( t=6.53, 13.17, both P<0.05). Three months after the intervention, the total score of SF-12 in the observation group was (65.96 ± 2.94) points, and the psychological dimension score was (37.50 ± 4.14) points, both of which were higher than those in the control group (60.30 ± 2.42) and (30.13± 5.15) points, and the differences were statistically significant ( t=51.54, 5.42, both P<0.05). There were statistically significant differences in time, between groups, and interaction effects in CES-D score, scores of two dimensions of BADS-SF and SF-12 total score ( F values were 10.04-190.71). Conclusions:Behavioral activation therapy can improve the symptoms of subthreshold depression in patients with diabetes foot amputation, enhance their behavioral activation level, and improve the quality of life to a certain extent.
4.Clinical transfusion consultation investigation and typical case analysis
Junlong YANG ; Yanli BAI ; Xuli DU ; Bin ZHANG ; Bo WANG
Chinese Journal of Blood Transfusion 2024;37(5):561-566,574
Objective To analyze the characteristics of blood transfusion consultation cases and establish the consulta-tion route,so as to provide reference for blood transfusion doctors to participate in blood transfusion consultation practice.Methods The cases involved in clinical transfusion consultation in the blood transfusion department of our hospital from 2020 to 2023 were collected from the hospital information system(HIS),and then classified by department and consultation type to summarize the main points of transfusion consultation,formulate transfusion consultation routes,and conduct typical cases analysis.Results There were 315 clinical transfusion consultations from 2020 to 2023,with an increasing trend year by year(26 in 2020,67 in 2021,81 in 2022,141 in 2023).The consultations involved 24 departments,including cardio-vascular medicine 14.0%(44/315),orthopedics 12.7%(40/315),intensive care medicine 8.9%(28/315),general medi-cine 8.3%(28/315),cardiopulmonary disease 6.0%(19/315),etc.There were 8 categories of consultations,including 35.6%(112/315)autologous ozonized blood transfusion,23.8%(75/315)plasma exchange,14.9%(47/315)perioperative mass blood preparation(transfusion),11.4%(36/315)platelet-rich plasma therapy and 6.3%(20/315)autologous blood collection,etc.The clinical blood transfusion consultation route was formulated according to the consultation points.Six pa-tients with various diseases were treated by blood transfusion department.With effective treatment measures taken,all of them improved and were discharged.Conclusion The summary of key points of clinical blood transfusion consultation and formulation of the blood transfusion consultation route by department of blood transfusion are conducive to the implementation of blood transfusion consultation and guarantee the safety of patients.
5.Differential bone metabolism and protein expression in mice fed a high-fat diet versus Daurian ground squirrels following natural pre-hibernation fattening.
Xuli GAO ; Shenyang SHEN ; Qiaohua NIU ; Weilan MIAO ; Yuting HAN ; Ziwei HAO ; Ning AN ; Yingyu YANG ; Yu ZHANG ; Han ZHANG ; Kenneth B STOREY ; Hui CHANG
Journal of Zhejiang University. Science. B 2022;23(12):1042-1056
This study compared the effects on bone metabolism and morphology of pathological obesity induced by excessive fat intake in a non-hibernator (mice) versus healthy obesity due to pre-hibernation fattening in a hibernator (ground squirrels). Kunming mice were fed a high-fat diet to provide a model of pathological obesity (OB group). Daurian ground squirrels fattened naturally in their pre-hibernation season (PRE group) were used as a healthy obesity model. Micro-computed tomography (micro-CT) and three-point bending tests were used to determine the microstructure and mechanical properties of bone. Western blots were used to analyze protein expression levels related to bone metabolism (Runt-related transcription factor 2 (RunX2), osteocalcin (OCN), alkaline phosphatase (ALP), osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), cathepsin K, matrix metallopeptidase 9 (MMP9), patched protein homolog 1 (Ptch1), phosphorylated β-catenin (P-β-catenin), and glycogen synthase kinase-3β (GSK-3β)). Compared with controls, there was no obvious bone loss in the OB mice, and the stiffness of the femur was increased significantly. Compared with summer active squirrels, bone formation was enhanced but the mechanical properties did not change in the PRE group squirrels. In OB mice, western blots showed significantly increased expression levels of all proteins except RunX2, OPG, and Ptch1. PRE ground squirrels showed significantly increased expression of most proteins except OCN and Ptch1, which decreased significantly, and P-β-catenin and OPG, which did not change. In conclusion, for non-hibernating mice, moderate obesity had a certain protective effect on bones, demonstrating two-way regulation, increasing both bone loss and bone formation. For pre-hibernating ground squirrels, the healthy obesity acquired before hibernation had a positive effect on the microstructure of bones, and also enhanced the expression levels of proteins related to bone formation, bone resorption, and Wnt signaling.
Mice
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Animals
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Hibernation
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Core Binding Factor Alpha 1 Subunit/metabolism*
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Glycogen Synthase Kinase 3 beta/metabolism*
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Diet, High-Fat
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X-Ray Microtomography
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Sciuridae/metabolism*
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Obesity
6.Effects of can walking anterior and posterior capsule polishing combined with tension ring implantation on lens capsular stability after phacoemulsification for ultra-high myopia cataract
Xuli ZHAO ; Lu WANG ; Ting LONG ; Ge HUANG ; Guang YANG
Chinese Journal of Microsurgery 2022;45(3):310-314
Objective:To observe the effects of polishing the anterior and posterior capsule with irrigation/aspiration (I/A) injection needle and capsular tension ring (CTR) implantation on intraocular lens (IOL) capsular stability after phacoemulsification for ultra-high myopia with 2.0 mm coaxial micro incision.Methods:This is a prospective randomized controlled study. There were 40 patients(80 eyes) aged 46-72 years old with ultra-high myopia cataract. The grade of lens opacity was grade II-IV, and the diopter was -10 D - -24 D. During 2.0 mm coaxial micro incision phacoemulsification, adopt coin tossing method randomly, 1 eye was operated using the anterior and posterior capsule polishing 360° with I/A injection needle combined with CTR implantation as the experimental group(40 eyes), the other eye was neither polished nor CTR implantated as the control group(40 eyes). The operation interval of both eyes was less than 1 week. The size of anterior capsular orifice, effective intraocular lens position(ELP), IOL eccentricity and posterior capsular opacification(PCO) were recorded at 1 week, 1, 3 and 6 months after operation in outpatient clinic. Two independent sample t-test and Fisher exact probability test were used to compare the differences between the 2 groups. P<0.05 was defined significant difference. Results:During the follow-up period, there were no significant change in the anterior capsule area, IOL eccentricity and ELP in the experimental group. However in the control group, the anterior capsular area decreased gradually with time, and gradually IOL eccentricity increased and ELP decreased. There was no significant difference between the 2 groups in each observation index at 1 week after operation, but it was ELP that first showed the difference tendency( P<0.01). The ELP of the control group was significantly lower than that of the experimental group at 1, 3 and 6 months after operation( P<0.05). There was no significant difference in anterior capsule area and IOL eccentricity between the 2 groups at 1 and 3 months after operation( P>0.05), but there was a significant difference at 6 months( P<0.05). In terms of PCO, the incidence of PCO was 0%, 2.5% and 7.5% in the experimental group and 5.0%, 17.5% and 32.5% in the control group respectively at 1, 3 and 6 months after operation. The incidence of PCO in the experimental group was significantly lower than that in the control group( P<0.05). Conclusion:Ultra-high myopia with cataract are prone to have capsular contraction after operation, which is characterized by IOL instability and anterior capsular orifice narrowing gradually. Combined 360° anterior and posterior capsular polishing with tension ring implantation in operation can effectively maintain the stability of ELP, reduce the degree of contraction of anterior capsular orifice, reduce the eccentricity of IOL and the incidence of PCO. Polishing the anterior and posterior capsule with I/A injection needle combined with CTR implantation, is safe and effective for patients with ultra-high myopia cataract.
7.Identification of potential anti-pneumonia pharmacological components of Glycyrrhizae Radix et Rhizoma after the treatment with Gan An He Ji oral liquid
Xiaojuan JIANG ; Yihua LIN ; Yunlong WU ; Caixia YUAN ; Xuli LANG ; Jiayun CHEN ; Chunyan ZHU ; Xinyi YANG ; Yu HUANG ; Hao WANG ; Caisheng WU
Journal of Pharmaceutical Analysis 2022;12(6):839-851
Glycyrrhizae Radix et Rhizoma,a traditional Chinese medicine also known as Gan Cao(GC),is frequently included in clinical prescriptions for the treatment of pneumonia.However,the pharmacological com-ponents of GC for pneumonia treatment are rarely explored.Gan An He Ji oral liquid(GAHJ)has a simple composition and contains GC liquid extracts and paregoric,and has been used clinically for many years.Therefore,GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia.We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days.Using the intelligent mass spectrometry data-processing technologies to analyze the meta-bolism of GC in vivo,we obtained 168 related components of GC in humans,consisting of 24 prototype components and 144 metabolites,with 135 compounds screened in plasma and 82 in urine.After analysis of the metabolic transformation relationship and relative exposure,six components(liquiritin,liquiritigenin,glycyrrhizin,glycyrrhetinic acid,daidzin,and formononetin)were selected as potential effective components.The experimental results based on two animal pneumonia models and the in-flammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase(iNOS).Interestingly,glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo.The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS.Thus,the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.
9.Study on screening for 274 suspected cases of corona virus disease 2019
Xuli YANG ; Zhihui WANG ; Xing LIU ; Shanshan WU ; Xiaoping WU ; Guilan WEN ; Xianjun ZENG ; Huawei XIONG ; Jie LIU ; Tao HONG
Chinese Journal of Infectious Diseases 2020;38(4):199-203
Objective:To evaluate the diagnostic efficacies of computed tomography (CT), clinical manifestations and 2019 novel coronavirus (2019-nCoV) nucleic acid test results for the screening and diagnosis of novel coronavirus pneumonia.Methods:The clinical data of suspected cases with corona virus disease 2019 (COVID-19) visited fever clinic or stayed in emergency room of the First Affiliated Hospital of Nanchang University from January 23 to February 9, 2020 were collected. Totally 274 cases who met the inclusion criteria were enrolled. Four screening schemes including chest CT screening, scoring, chest CT and scoring series screening, chest CT and scoring parallel screening were designed. The statistical analysis was performed by using chi-square test. The sensitivities, specificities and the areas under the receiver operator characteristic curve of the four screening schemes were calculated, and the diagnostic efficacies were evaluated.Results:Among the 274 cases, 93.80%(257/274) presented with typical clinical symptoms, 47.81%(131/274) had epidemiological history, and the blood routine examination results of 45.26%(124/274) cases met the positive criteria of the scoring , and chest CT results of 43.07%(118/274) cases met the positive criteria of chest CT screening. The 2019-nCoV nucleic acid test positive rate of cases with epidemiological history was 30.53%(40/131), which was higher than that of cases without epidemiological history (9.09%(13/143)), and that of cases with typical imaging performance on chest CT was 40.68%(48/118), which was higher than cases without typical imaging performance (3.21%(5/156)). The differences between the above groups were both statistically significant ( χ2=20.150、60.468, respectively, both P<0.01). The positive rates of viral nucleic acid detection in cases with positive findings of chest CT screening, scoring, series screening, and parallel screening were 40.68%(48/118), 23.74%(47/198), 44.68%(42/94) and 23.87%(53/222), respectively, while those in cases with negative findings of the four screening schemes were 3.20%(5/156), 7.89%(6/76), 6.11%(11/180) and 0(0/52), respectively. The positive rates of the four screening schemes were all significantly different from that of viral nucleic acid detection ( κ=0.402, 0.100, 0.431, 0.106, all P<0.01). The chest CT screening method had a sensitivity of 90.57%and a specificity of 68.33%, and an area under the operating characteristic curve of the subject was 0.794, which had higher diagnostic value than those of the other three screening schemes. Conclusions:For the screening and diagnosis of COVID-19 cases, epidemiological history, positive 2019-nCoV nucleic acid test with ≥2 typical clinical manifestations have highly diagnostic value. On the basis of the preliminary screening of chest CT examination, flexible analysis of the diagnostic results could improve the diagnostic value of each detection method.
10.Changes and significance of serum TPS and ILG6 after TACE treatment of hepatocellular carcinoma
Xuli MIN ; Hao XU ; Lin YANG ; Hanfeng YANG ; Yongjun REN
Journal of Practical Radiology 2019;35(10):1603-1606
Objective To explore the changes of serum tryptase(TPS)and interleuk-6 (IL-6)levels before and after TACE treatment in patients with hepatocellular carcinoma (HCC).Methods ELISA was used to detect the serum TPS and IL-6 levels in 5 1 patients with HCC 1 day before and 1 day,1 week and 1 month after TACE.30 healthy people were enrolled as a control group.Results Serum TPS and IL-6 levels in observation group before TACE were higher than those in control group (P<0.05),and serum TPS level in the observation group was positively correlated with serum IL-6 level (P<0.05)before TACE.Serum TPS and IL-6 levels in the response group one month after TACE were lower than those one day before TACE (P<0.05),while compared with those one day before TACE ,the non-response group increased slightly and non significance was showed(P>0.05).Conclusion Serum TPS and IL-6 levels are closely related to the response of HCC to TACE treatment,thus these may be used to evaluate the efficacy of TACE in treatment of HCC.

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