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.

OBJECTIVE To compare the general status of training programs for geriatric clinical pharmacists in China and the United States， and provide a reference for further optimizing training programs of geriatric clinical pharmacists in China. METHODS Retrieved from the American Society of Health-System Pharmacists （ASHP） website and the Chinese Hospital Association website， the detailed information and data on training outline， institution type/scale， enrollment number， training contents， project application conditions and graduation assessments for clinical pharmacists in geriatric field were collected and statistical analysis was performed using Excel software. RESULTS & CONCLUSIONS As of January 12， 2024， ASHP provided 24 geriatric clinical pharmacist training programs and 25 positions available for application in the postgraduate year two training， which provided compensation. The training base involved hospitals and pharmaceutical colleges， with varying scales. Applicants needed to obtain a doctor of pharmacy and complete postgraduate year one training. ASHP had designed detailed training objectives for the four essential skills of basic patient care， advanced patient care， leadership and management skills， and knowledge education and teaching dissemination. Each training base could appropriately add optional skills such as academic skills， long-term care skills and other skills according to its characteristics， developed a student rotation plan， and conducted assessments and evaluations at multiple time points during the training process. There were 5 training programs for geriatric clinical pharmacists in China， with 15 positions， which didn’t provide compensation； training bases were all third-grade class A hospitals with relatively large scale. The applicant needed to obtain a bachelor’s degree or above， and different years of work were required based on their major and degree level. The Pharmaceutical Specialized Committee of the China Hospital Association had established a detailed training outline， proposing specific training objectives on theoretical knowledge， practical skills， scientific research thinking， etc. The training base organized assessments and evaluations at the time of enrollment， completion of specified content training， and graduation. According to the experience of the US， it is recommended to provide differentiated knowledge and skills training for students at different levels， flexibly arrange rotating departments， require students to work independently and deeply participate in clinical teaching and research work， conduct multiple and various forms of assessments， and adjust learning plans in a 13264273306@126.com timely manner to comprehensively enhance their abilities.

OBJECTIVE To investigate the effect of bs-5-YHEDA iron chelating peptide combined with semaglutide on the cognitive ability and pathological characteristics of D-Gal-induced Alzheimer's disease(AD) model mice. METHODS Forty mice were randomly divided into 5 groups, namely the healthy control group, PBS group, bs-5-YHEDA iron chelating peptide group, combined treatment group and positive control group, with 8 mice in each group, half of each sex. Except for the healthy control group, D-galactose was injected to induce the AD mice model for 6 weeks. For 3 consecutive weeks starting from the 4th week, the bs-5-YHEDA iron chelating peptide group was injected with bs-5-YHEDA(1 mg·mL–1) once every other day at 200 µL in the tail vein; the bs-5-YHEDA iron chelating peptide(1 mg·mL–1) and semaglutide(25 nmol·kg–1·d–1) were given alternately once a day in the combination treatment group; the positive control group was given memantine(3.3 mg·kg–1·d–1) by gavage every other day. The healthy control group and PBS group were injected with the equal dose of PBS. At the end of treatment, the learning memory ability of mice was detected by the Morris water maze method, whole brain and whole blood were dissected, and pathological changes in hippocampal region were observed by HE staining, and Aβ expression and Tau protein phosphorylation levels were detected by immunohistochemistry, enzyme-linked immunosorbent assay and immunoblotting. RESULTS In the Morris water maze spatial exploration experiment, the differences in the number of times the mice traversed the platform, the ratio of swimming distance to the target quadrant, and the time ratio were statistically significant in each group(P<0.05); compared with the PBS group, the ratio of swimming distance to the target quadrant increased in the combined treatment group, and the differences were statistically significant(P<0.05). The results of HE staining showed that compared with the healthy control mice, the hippocampal area in the PBS group showed reduced levels of pyramidal cells, disorganized arrangement, cell edema, and deep staining of nuclei consolidation. Cellular disorganization, deep staining of nuclei and apoptosis in the hippocampus were significantly improved in each treatment group after drug treatment. Immunohistochemistry and Western blotting results showed that the Aβ expression levels and Tau protein phosphorylation levels were significantly higher in the PBS-administered mice compared with the healthy control mice, and the Aβ expression levels and Tau protein phosphorylation levels were reduced in each group after drug treatment, with statistically significant differences(P<0.01 or P<0.001 ). CONCLUSION The combination of bs-5-YHEDA iron chelating peptide and semaglutide can effectively improve the learning and memory ability and pathological characteristics of AD mice, but from the results of immunohistochemistry and immunoblotting experiments, the improvement of pathological characteristics of AD mice in the combination treatment group is not obvious compared with the single bs-5-YHEDA iron chelating peptide group, suggesting that there may be a threshold effect of our designed dual-target combination treatment on the cognitive improvement of AD mice, and the optimization and validation of the effect of multi-target combination treatment need further study.

Objective To compare the value of standard coronal MRI and multi-planar reconstruction(MPR)images for evaluation of anterolateral ligament(ALL).Methods Data of 130 patients who underwent knee joint MR examination were retrospectively analyzed,including standard coronal MRI and MPR images.ALL were identified on standard coronal MRI and MPR images and classified as fully visible,partially visible or invisible.The visibility of bilateral ALL on both standard coronal MRI and MPR images were compared,while Kappa test was used to evaluate the consistency on both kinds of images.Results Among 130 cases,on standard coronal MRI and MPR images,the left ALL was fully visible in 83 and 93 cases,partially visible in 21 and 12 cases but invisible cases in 26 and 25 cases,respectively,while the right side ALL was fully visible in 66 and 80 cases,partially visible cases in 29 and 15 cases but invisible cases each in 35 cases,respectively.Significant difference of visibility of bilateral ALL were found between standard coronal MRI and MPR images(both P＜0.05),both with excellent consistency(both Kappa＞0.80).Conclusion MPR could display bilateral ALL better than standard coronal MRI.If the scanning conditions for MPR could not be met,standard coronal MRI might be used to evaluate ALL rather accurately.

Objective To establish an immortalized tree shrew corneal stromal cells(CSCs)line and to study its response to virus infection.Methods Primary tree shrew CSCs were isolated and cultured by the tissue block adhesion method.CSCs were then transfected with a lentivirus carrying the SV40T gene and monoclonal cells were selected for passage culture.The characteristics of the CSCs were investigated by morphological observation and compared with 40 generations until the 50 generations or more,immunofluorescence identification of vimentin and SV40T genes,karyotype examination,and cell proliferation curve.The CSCs were infected with herpes simplex virus-1(HSV-1)(McKrae strain),Zika virus(ZIKV,GZ01 strain),Dengue virus typeⅡ,and H1N1(PR8).Results The immortalized tree shrew CSCs after＞50 passages appeared spindle-shaped with good cell morphology and structure compared with 40 generations.Positive immunofluorescence expression of vimentin and SV40T genes.The cell growth curve showed that the cells were in logarithmic-phase growth on days 4～5 and grew vigorously.The number of chromosomes in the primary cells was stable at 62,while immortalized CSCs had 64 chromosomes at P21 and P56.The virus titer results showed that the immortalized tree shrew CSCs were sensitive to HSV-1(McKrae strain),ZIKV(GZ01 strain),Dengue virus typeⅡ,and H1N1(PR8),with virus titers of 1.32×105,5.62×106,2.69×107,and 7.76×104 CCID50/mL,respectively.Conclusions The immortalized tree shrew CSCs were established successfully,suggesting that this cell line is suitable for studies of the mechanisms of HSV,ZIKV,Dengue virus,and influenza A virus infection in relation to corneal diseases and antiviral drugs.

AIM:To investigate the effect of a disintegrin and metalloproteinase(ADAM)domain-like decy-sin 1(ADAMDEC1)knockdown on the proliferation,migration and invasion of pancreatic carcinoma cells.METHODS:Expression levels of ADAMDEC1 in pancreatic carcinoma tissues were analyzed using the GEPIA and UALCAN online da-tabases.Western blot analysis was employed to detect the protein expression levels of ADAMDEC1 in pancreatic carcino-ma cell lines(MIA PaCa-2 and PANC-1)and pancreatic ductal cell line(hTERT-HPNE).The effects of ADAMDEC1 knockdown on cell proliferation,migration and invasion were evaluated using CCK-8,colony formation,wound-healing and Transwell assays.Additionally,Western blot analysis was used to detect the effects of ADAMDEC1 knockdown on the expression levels of migration and invasion markers,as well as Wnt/β-catenin signaling pathway-related proteins in pancre-atic carcinoma cells.Furthermore,a recovery experiment was conducted to assess the role of Wnt/β-catenin signaling path-way agonist CHIR-99021 in ADAMDEC1 knockdown-induced inhibition of pancreatic carcinoma cell growth and migra-tion.RESULTS:(1)ADAMDEC1 was highly expressed in pancreatic carcinoma cells.(2)Knockdown of ADAMDEC1 led to a significant reduction in the proliferation,migration and invasion of pancreatic carcinoma cells.(3)Knockdown of ADAMDEC1 resulted in increased E-cadherin protein expression and decreased levels of matrix metalloproteinase 9,N-cadherin and vimentin proteins,alongside a reduction in the expression of Wnt/β-catenin signaling pathway-related pro-teins.(4)Co-treatment of pancreatic carcinoma cells with CHIR-99021 and ADAMDEC1 small interfering RNA reversed the inhibitory effects of ADAMDEC1 knockdown on cell proliferation,migration,and invasion.CONCLUSION:ADAMDEC1 is highly expressed in pancreatic carcinoma.Targeted silencing of ADAMDEC1 has the potential to inhibit the prolifera-tion,migration and invasion of pancreatic carcinoma cells by regulating the Wnt/β-catenin signaling pathway.

Turner syndrome is a sex chromosome disease with a female clinical phenotype.Most pa-tients are diagnosed in childhood or adolescence because of growth delays,and a small number of patients are diagnosed due to TS-related diseases.Women with Turner syndrome can develop hyper-tension in childhood and adolescence,and the prevalence of hypertension increases with age.The pathogenesis is unclear and may be multifactorial,similar to essential hypertension.In this review arti-cle,we explore possible mechanisms,blood pres-sure management,and treatment recommenda-tions for hypertension in patients with Turner syn-drome.

Objective:To analyze and evaluate the safety and efficacy of a Chinese domestically manufactured Heart Con-type implantable third-generation magnetic and hydrodynamic levitation left ventricular assist device(LVAD) for the treatment of end-stage heart failure(ESHF), by reporting the results of eleven-center clinical trial on 50 cases.Methods:This study was a multicenter clinical trial, designed by means of prospective, multicenter and single-group target value. 50 subjects with ESHF were competitively enrolled and treated with HeartCon as the LVAD in eleven centers. The primary efficacy measure was survival, defined as either the subjects experiencing the transition to heart transplantation(HT) or myocardial recovery assisted by the device within 90 days, or as successfully assisted by the LVAD for full 90 days after implantation. The target survival rate was 60%, other observations included implantation success rate, mortality, pump failure needing replacement or emergency heart transplantation.Results:All enrolled 50 patients received LVAD implantation successfully, 46 survived with the pump for 90 days, 1 patient transitioned to heart transplantation, and 3 patients experienced pump thrombosis, within which 2 patients underwent pump replacement and continued to live with the pump for 90 days, and the other one received emergency heart transplantation. There were no dropout subjects. The survival rate at full 90 days after HeartCon implantation was 100%. The survival rates with pump in the full set analysis and the protocol set analysis were 96.00% and 95.92% respectively, which were higher than the target value of 60%. The differences were both statistically significant( P<0.05). Conclusion:The results of the multicenter clinical trial with the largest sample size in China using domestically manufactured third-generation LVAD has demonstrated that, HeartCon is a safe and effective LVAD to treat ESHF patients.

A new class of potent liver injury protective compounds, phychetins A-D ( 1- 4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2- 4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1- 4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2- 4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1β. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.

Objective:To figure out the timing of zeroing and the location of the zero line in the central venous pressure (CVP) monitoring and invasive arterial blood pressure (IBP) monitoring, and to provide scientific and accurate data for patients management.Methods:The liquid vessel models were used to simulate the pressure measurement process of the continuous pressure monitoring system. Based on the theory of fluid mechanics and the knowledge of blood pressure physiology and cardiovascular anatomy, the composition and influencing factors of the pressure in the fluid-filled catheter system during the zeroing and placing the transducer in the zero line of CVP and IBP, were analyzed.Results:The pressure in the liquid-filled catheter system was composed of atmospheric pressure, the pressure of pumping bag, the gravity of the water column (the vertical distance between the liquid level of Murphy's dropper and pressure transducer, ΔH), and the resistance of tube wall. This pressure value is set as a pressure of 0 mmHg (1 mmHg ≈ 0.133 kPa). In the process of pressure measurement, when the pressure transducer was placed at a horizontal position of 10 cm below the highest liquid level of the vessel, the pressure measured at different catheter tip positions was all 10 cmH 2O (1 cmH 2O ≈ 0.098 kPa); When the pressure transducer was placed at the horizontal position of the highest liquid level of the vessel, the measured pressure is 0 mmHg. Conclusion:Zeroing should repeatedly be performed only when one or more conditions (atmospheric pressure, pressure of pumping bag, gravity of ΔH water column and resistance of tube wall) are changed. In the measurement process, the pressure transducer should be placed at the zero line position at any time to eliminate the influence of hydrostatic pressure and to ensure the objective and accurate value.