The study aims to explore the methods for preparing nanocomplexes of Prussian blue nanoparticles (PBNPs) with UNO peptide (UNO-PBNPs) and the functions of the nanocomplexes targeting M2-type macrophages in vitro. PBNPs were prepared by the hydrothermal synthesis method. Subsequently, the peptide UNO (CSPGAKVRC) targeting the mannose receptor was modified on their surface by a heterobifunctional coupling approach. The morphological characteristics of nanoparticles were observed by scanning and transmission electron microscopy. Additionally, their particle size, Zeta potential, and dispersion stability were assessed. The structural characteristics of nanoparticles were analyzed by X-ray diffraction and other techniques. The biological safety of the nanoparticles was evaluated by the CCK-8 assay and hemolysis experiments. Moreover, the targeting performance of UNO-PBNPs towards M2-type macrophages was assessed in vitro. The results showed that the synthesized UNO-PBNPs exhibited uniform cubic morphology, with an average particle size of (202.00±4.21) nm. They were negative charged, well dispersed, and stable. At concentrations ≤ 200 μg/mL, the synthesized UNO-PBNPs led to the hemolysis rate below 5%, demonstrating excellent biocompatibility. The laser confocal imaging results showed that after co-incubation with M2-type macrophages, the FITC-labeled UNO-PBNPs were effectively accumulated in the cells, presenting a distinct fluorescence signal. Quantitative analysis by flow cytometry showed that the intracellular mean fluorescence intensity (6 019.00±346.04) of UNO-PBNPs was higher than that (4 054.00±379.14) of unmodified PBNPs (P < 0.001). In summary, the UNO-PBNPs prepared in this study exhibited a targeting effect on M2-type macrophages, providing a potential method for targeted delivery of PBNPs in the tumor microenvironment and laying a foundation for the remodeling of the tumor immunosuppressive microenvironment.
Ferrocyanides/chemistry* ; Nanoparticles/chemistry* ; Macrophages/drug effects* ; Peptides/chemistry* ; Particle Size ; Animals ; Mannose Receptor ; Mice ; Lectins, C-Type ; Mannose-Binding Lectins ; Receptors, Cell Surface

Objective To identify the current research hotspots of global health training, and construct a global health talent training evaluation index system. Methods Publications pertaining to global health talent training evaluation were retrieved in China National Knowledge Infrastructure, Wanfang Database, and Web of Science Core Collection from 2003 to 2022, and keywords were extracted from eligible publications for co-occurrence and cluster analyses using the CiteSpace software. Based on keywords clustering results, a global health talent training evaluation index system was constructed using a context, input, process, and product (CIPP) evaluation model as a theoretical framework. Results A total of 692 Chinese publications and 1 264 English publications were included. Keyword co-occurrence and cluster analyses yielded 10 Chinese and 10 English keyword clusters, and the 10 Chinese keyword clusters included analytic hierarchy process, health diplomacy, personnel structure, crossdiscipline, educational assessment, global health discipline development, training needs, curriculum program, quality evaluation and logistics support, while the English keyword clusters included evidence-based practice, capacity building, global health, quality of life, machine learning, leadership, sub-Saharan Africa, health equity, global health security and global health diplomacy. Based on keyword clustering, a global health talent training evaluation index system was constructed with CIPP as the theoretical framework, which contained 4 primary indicators, 15 secondary indicators and 59 tertiary indicators, and the primary indicators included 4 dimensions of context evaluation, input evaluation, process evaluation and product evaluation. Conclusions A global health talent training evaluation index system has been constructed, which provides an effective evaluation tool and quantitative evidence for future global health talent training.

Objective To standardize nursing management on postoperative patients with a left ventricular assist-ant device(LVAD).Methods The first draft of the Consensus was formed on the basis of literature review.2 rounds of expert consultations and a round of online meeting discussion were held for adjustments and modifications the draft of the Consensus.Results The recovery rate of the inquiry questionnaire was 93.75%.The authority coefficients of the 2 rounds of inquiry experts were 0.927 and 0.920.The concentration degree of expert opinions for each indicator was greater than 3.5 score,and the coefficient of variation was less than 0.25.The Kendall harmony coefficients for 2 rounds of correspondence were 0.402 and 0.407(P<0.01).The final Consensus formed through expert consultations and meetings includes 7 themes:hemodynamic monitoring,LVAD function monitoring,coagulation function monitoring,percutaneous cable and wound care,exercise rehabilitation care,health education and guidance,and pre-discharge assessment.Conclusion The Consensus is scientific,rigorous,and authoritative.The Consensus covers all aspects of postoperative care for patients with LVAD,and it will benefit to clinical practice.

This article summarizes Professor TIAN Conghuo's key points and features of acupuncture for primary dysmenorrhea. Professor TIAN believes that the location of dysmenorrhea is in the uterus, and the fundamental pathogenesis is the disharmony of both form and spirit. During clinical treatment, he first conducts abdominal palpation, often detecting cord-like nodules around Guilai (ST 29), Huangshu (KI 16), and Zigong (EX-CA 1). Needling reaches the depth of these nodules. Additionally, the use of four acupoints around the navel (Shuifen [CV 9], bilateral Huangshu (KI 16), and Yinjiao [CV 7]), and four back-shu points (Ganshu [BL 18], Pishu [BL 20], Shenshu [BL 23], and Geshu [BL 17]) is applied to regulate the spirit and strengthen the body. Point selection is further based on syndrome differentiation. The "Three layers" needling technique is used, emphasizing the mental and emotional state of the patients, calming the spirit and regulating qi and blood, to achieve a harmonious treatment of both form and spirit for dysmenorrhea.
Adult ; Female ; Humans ; Acupuncture Points ; Acupuncture Therapy ; Dysmenorrhea/therapy*

OBJECTIVE: To investigate the anti-adhesive effect and underlying mechanism of dynamic and static stress stimulation on the early healing process of rat Achilles tendon injury. METHODS: Achilles tendon tissues of 15 male Sprague Dawley (SD) rats aged 4-6 weeks were isolated and cultured by enzyme digestion method. Rat Achilles tendon cells were treated with tumor necrosis factor α to construct the Achilles tendon injury cell model, and dynamic stress stimulation (dynamic group) and static stress stimulation (static group) were applied respectively, while the control group was not treated. Live/dead cell double staining was used to detect cell activity, ELISA assay was used to detect the expression of α smooth muscle actin (α-SMA), and real-time fluorescence quantitative PCR was used to detect the mRNA expression of collagen type Ⅰ (COL1A1), collagen type Ⅲ (COL3A1), and Scleraxis (SCX). Thirty male SD rats aged 4-6 weeks underwent Achilles tendon suture and were randomly divided into dynamic group (treated by dynamic stress stimulation), static group (treated by static stress stimulation), and control group (untreated), with 10 rats in each group. HE staining and scoring were performed to evaluate the healing of Achilles tendon at 8 days after operation. COL1A1 and COL3A1 protein expressions were detected by immunohistochemical staining, α-SMA and SCX protein expressions were detected by Western blot, and maximum tendon breaking force and tendon stiffness were detected by biomechanical stretching test. RESULTS: In vitro cell experiment, when compared to the static group, the number of living cells in the dynamic group was higher, the expression of α-SMA protein was decreased, the relative expression of COL3A1 mRNA was decreased, and the relative expression of SCX mRNA was increased, and the differences were all significant ( P<0.05). In the in vivo animal experiment, when compared to the static group, the tendon healing in the dynamic group was better, the HE staining score was lower, the expression of COL1A1 protein was increased, the expression of COL3A1 protein was decreased, the relative expression of SCX protein was increased, the relative expression of α-SMA protein was decreased, and the tendon stiffness was increased, the differences were all significant ( P<0.05). CONCLUSION Compared with static stress stimulation, the dynamic stress stimulation improves the fibrosis of the scar tissue of the rat Achilles tendon, promote the recovery of the biomechanical property of the Achilles tendon, and has obvious anti-adhesion effect.
Animals ; Achilles Tendon/injuries* ; Male ; Rats ; Rats, Sprague-Dawley ; Collagen Type I/metabolism* ; Collagen Type III/metabolism* ; Tendon Injuries/therapy* ; Wound Healing ; Stress, Mechanical ; Actins/metabolism* ; Cells, Cultured ; Tissue Adhesions/prevention & control* ; Tumor Necrosis Factor-alpha/metabolism* ; RNA, Messenger/genetics* ; Disease Models, Animal ; Collagen Type I, alpha 1 Chain/metabolism* ; Biomechanical Phenomena ; Basic Helix-Loop-Helix Transcription Factors

Objectives:To investigate the effect of resistance exercise(RE)on the dissolution of catheter-associated thrombus(CRT)and its possible mechanism.Methods:A total of 36 male SD rats were randomly divided into control group,CRT group,CRT+ RE group(n=12 in each group).Rats in the CRT group did not receive any intervention,while rats in the CRT+RE group received RE intervention 10 days after modeling for 28 days.The thrombolysis rate was evaluated by Hematoxylin-Eosin staining.The contents of irisin,interleukin(IL)-6 and IL-10 in serum were detected by ELISA.The relative mRNA expression levels of peroxisome proliferator-activated receptor γ coactivator α(PGC-1α)and fibronectin type Ⅲ domain-containing 5(FNDC5)in gastrocnemius were detected by real-time quantitative PCR(qPCR).Results:There was no thrombosis in control group.Compared with control group,the contents of irisin and IL-10 in CRT group were significantly decreased,while the content of IL-6 in CRT rats was significantly increased(all P<0.01).Thrombolysis rate was significantly higher,and the mRNA expressions of PGC-1α and FNDC5 in gastrocnemius were significantly upregulated in CRT+RE group than in CRT group(all P<0.01).Serum irisin,IL-10 contents were significantly increased,IL-6 content was significantly lower in CRT+RE group than in CRT group(all P<0.01).Conclusions:Resistance exercise for 28 days could promote the dissolution of CRT,which may be related to the up-regulation of irisin expression and the inhibition of inflammation.

To conduct the association between vitamin B12 and mental health in children and adolescents. Five databases were searched for observational studies in any language reporting on mental health and vitamin B12 levels or intake in children and adolescents from inception to March 18, 2022. Two authors independently extracted data and assessed study quality. Qualitative and quantitative analysis of data were performed. The review was registered in the PROSPERO database (CRD42022345476). Fifty six studies containing 37,932 participants were identified in the review. Vitamin B12 levels were lower in participants with autism spectrum disorders (ASD) (standardized mean difference [SMD], −1.61;95% confidence interval [95% CI], −2.44 to −0.79; p ＜ 0.001), attention deficit hyperactivity disorders (SMD, −0.39; 95% CI, −0.78 to −0.00; p = 0.049) compared with control group. Vitamin B12 intake were lower in participants with ASDs (SMD, −0.86; 95% CI, −1.48 to −0.24; p = 0.006) compared with control group, but showed no difference between depression group (SMD, −0.06; 95% CI, −0.15 to 0.03; p = 0.17) and the control group. Higher vitamin B12 intake were associated with lower risk of depression (odds ratio [OR], 0.79; 95% CI, 0.63−0.98; p = 0.034) and behavioral problems (OR, 0.83; 95% CI, 0.69−0.99; p = 0.04). The vast majority of included studies supported potential positive influence of vitamin B12 on mental health, and vitamin B12 deficiency may be a reversible cause for some mental health disorders in children and adolescents.

Objective: More than 75% of ovarian cancer patients are diagnosed at advanced stages and die of tumor cell metastasis. This study aimed to identify new epigenetic and transcriptomic alterations associated with ovarian cancer metastasis. Methods: Two cell sublines with low- and high-metastasis potentials were derived from the ovarian cancer cell line A2780. Genome-wide DNA methylome and transcriptome profiling were carried out in these two sublines by Reduced Representation Bisulfite Sequencing and RNA-seq technologies. Cell-based assays were conducted to support the clinical findings. Results: There are distinct DNA methylation and gene expression patterns between the two cell sublines with low- and high-metastasis potentials. Integrated analysis identified 33 methylation-induced genes potentially involved in ovarian cancer metastasis. The DNA methylation patterns of two of them (i.e., SFRP1 and LIPG) were further validated in human specimens, indicating that they were hypermethylated and downregulated in peritoneal metastatic ovarian carcinoma compared to primary ovarian carcinoma. Patients with lower SFRP1 and LIPG expression tend to have a worse prognosis. Functionally, knockdown of SFRP1 and LIPG promoted cell growth and migration, whereas their overexpression resulted in the opposite effects. In particular, knockdown of SFRP1 could phosphorylate GSK3β and increase β-catenin expression, leading to deregulated activation of the Wnt/β-catenin signaling. Conclusion Many systemic and important epigenetic and transcriptomic alterations occur in the progression of ovarian cancer. In particular, epigenetic silencing of SFRP1 and LIPG is a potential driver event in ovarian cancer metastasis. They can be used as prognostic biomarkers and therapeutic targets for ovarian cancer patients.

OBJECTIVE To explore the current status and challenges of informatization construction for clinical trial centralized pharmacy based on the relevant experience of The First Affiliated Hospital, Zhejiang University School of Medicine. METHODS Review the development of clinical trial drug management and informatization process, along with the management experience of the hospital where the author works, and then introduce the framework and specific operation details of the informatization system when conducting centralized management method, summarize the problems encountered at present and propose future prospects. RESULTS Informatization construction played a significant role in the management of central pharmacies in clinical trial, enabling them to adapt to the complex management needs of investigational products and meet the high standards and strict requirements of Good Clinical Practice(GCP) and related regulations. However, the development of the current information system was still not perfect, and there were problems that need to be solved. CONCLUSION Each hospital needs to pay attention to the informatization construction of the central pharmacy of the clinical trial, improve and perfect the centralized management method of the investigational products, and explore modern technologies and equipments, which are of immense importance for the construction of the clinical trial pharmacy management that conforms to the development trend of drug clinical trials and GCP.

OBJECTIVE To optimize the extraction technology fo r phenylethanol glycosides from Cistanche deserticola by natural deep eutectic solvents （NADESs），and to provide reference for the development and utilization of C. deserticola . METHODS The optimal NADESs was selected using total extraction efficiency of echinacoside ，acteoside and isoacteoside as indexes. Based on single factor test ，response surface methodology was used to select the optimal NADESs molar ratio ，the optimal NADESs water content ，the optimal liquid-solid ratio ；and the results were optimized by genetic algorithm . Using vitamin C （VC） as positive control ，the extraction effects of NADESs and traditional solvent （50％ methanol）were compared in respects of extraction efficiency and antioxidant activities. RESULTS The optimal extraction solution was NADES- 11 composed of 1， 4-butanediol and malonic acid. The optimal extraction technology was as follows as the molar ratio of 1，4-butanediol-malonic acid was 1 ∶ 2.5，water content of NADES- 11 was 18％，liquid-solid ratio was 30 mL/g，extraction time was 30 min and extraction temperature was 30 ℃. The extraction efficiency of NADES- 11 was significantly higher than that of 50％ methanol（P＜0.05）. IC 50 values of NADES- 11 extract（261.17 and 744.34 µg/mL）to 1，1-diphenyl-2-trinitrophenylhydrazine radical and hydroxyl radical were all lower than those of 50％ methanol extract （420.97 and 1 175.12 μg/mL）. Ascorbic acid equivalent antioxidant capacity of Δ 基金项目 内蒙古自治区科技创新引导项目（No.00120209）；内 NADES-11 extract（17.19 and 360.80 mg VC/g ）was higher 蒙古自治区自然科学基金资助项目 （No.2021MS08011）；内蒙古自治 than that of 50％ methanol extract （10.67 and 228.54 mg 区医疗卫生科技计划项目（No.202201367）；包头医学院“花蕾计划”项 VC/g）. CONCLUSIONS The optimized extraction process of 目（No.HL2021046） phenylethanol glycosides from C. deserticola using NADESs is ＊第一作者 硕士研究生。研究方向：中蒙药药效成分。E-mail： environmental，stable and feasible. dongjiani369@126.com