Objective: To explore the nursing experience of growth hormone provocative test in pediatric clinic. Methods: Five thousand and thirty-six children with short stature or slowing growth received combined simultaneous Levodopa Pyridostigmine stimulation test from June 2008 to October 2018 in the Child Growth Center of the First Affiliated Hospital of SUN Yat-sen University. Comprehensive nursing intervention was conducted to ensure the test carry through successfully before, during and after the test. Results: All children completed the five collections in the 120-minute growth hormone provocative test without cannula obstruction and blurt out. Some (986 out of 5 036 children, 19.58%) had different degrees of adverse reactions including nausea, vomiting, abdominal pain, sweating, salivation, dizziness, pallor, etc., most of which disappeared or alleviated after nursing, except 11 patients (0.22%) needed atropine muscular injection and 3 of whom needed intravenous fluids to release the marked symptoms. Conclusion Combined simultaneous Levodopa Pyridostigmine stimulation test is safe and practicable in pediatric clinics with nursing experience.

Objective To evaluate the effect of sevoflurane anesthesia on the expression of hippocampal α4 subunit-containing nicotinic acetylcholine receptor (α4nAChR) in rats.Methods One hundred and forty-four Sprague-Dawley rats of both sexes,aged 3-4 months,weighing 220-270 g,were divided into 4 groups (n =36 each) using a random number table:control group (group C),sevoflurane anesthesia for 1 h group (group S1),sevoflurane anesthesia for 3 h group (group S2) and sevoflurane anesthesia for 5 h group (group S3).Group C inhaled air,and S1,S2 and S3 groups inhaled 3％ sevoflurane for 1,3 and 5 h,respectively.Twelve rats in each group were selected at 1 and 7 days after emergence from anesthesia to undergo spatial probe test.Rats were then sacrificed immediately after anesthesia and at 1 and 7 days after emergence from anesthesia,and hippocampi were removed for determination of the expression of α4nAchR protein and mRNA in hippocampal neurons (by Western blot or real-time polymerase chain reaction).Results Compared with group C,the duration of staying at the target quadrant was significantly shortened,and the ratio of duration of staying at the original platform quadrant to the total duration and ratio of swimming distance in the original platform quadrant to the total distance were decreased on 1 and 7 days after emergence from anesthesia,the expression of α4nAchR protein and mRNA was down-regulated,and the number of positive cells was reduced in S1,S2 and S3 groups (P＜0.05).Compared with S1 and S2 groups,the duration of staying at the target quadrant was significantly shortened,the ratio of duration of staying at the original platform quadrant to the total duration and ratio of swimming distance in the original platform quadrant to the total distance were decreased on 1 day after emergence from anesthesia in group S3 (P＜0.05).There was no significant difference in the expression of α4nAchR protein and mRNA or number of positive cells at each time point between group S1,group S2 and group S3 (P＞0.05).Conclusion The mechanism by which sevoflurane anesthesia induces cognitive dysfunction may be partially related to down-regulating the expression of hippocampal α4nAchR in rats.

Objective:To explore the value of matrix metalloproteinase (MMP) in differential diagnosis of brucellosis spondylitis (BS) and tuberculous spondylitis (TS).Methods:Retrospective analysis was used to collect the data of patients with BS and TS diagnosed in the First Affiliated Hospital of Xinjiang Medical University from January 2016 to December 2018. Magnetic resonance imaging (MRI), laboratory data, and the expression levels of MMP-2 and MMP-9 were analyzed.Results:There existed significant differences in imaging findings like the infection levels, the number of infected vertebrae and the paravertebral soft tissue lesions between BS and TS patients ( n=26, 27, P < 0.05). Basophils in BS patients were significantly higher than those in TS patients [(0.022±0.019) × 10 9 number/L vs (0.017±0.007) × 10 9 number/L, t=2.19, P < 0.05]; but the C-reactive protein of BS patients was significantly lower than that of TS patients [(16.12±14.16) mg/L vs (33.78±24.05) mg/L, t=2.45, P < 0.05]. The expression of MMP-9 in BS patients was significantly lower than that in TS patients [76.92% (20/26) vs 96.30% (26/27), χ 2=4.34, P < 0.05], but there was no significant difference in the expression of MMP-2 ( P > 0.05). Conclusion:MMP-9 may be a new biomarker in differential diagnosis of BS and TS, which can be helpful for the differential diagnosis of BS and TS by combining MRI findings with laboratory findings.

Objective:To investigate the expression of IL-18, IL-18-binding protein a(IL-18BPa) and IL-18 receptor α(IL-18Rα) by peripheral blood CD4 + Th17 cells of patients with allergic rhinitis (AR) and the effects of allergens on their expression. Methods:This study enrolled 45 outpatients with AR and 23 healthy control subjects receiving physical examination in the First Affiliated Hospital of Jinzhou Medical University from October 2019 to September 2020. According to the results of skin prick test, the 45 patients were divided into two groups: AR group with positive results (24 cases) and nAR group with negative results (21 cases). Blood samples of them were collected. Flow cytometry was used to analyze the effects of allergens on the expression of IL-18, IL-18BPa and IL-18Rα at protein level by peripheral blood CD4 + Th17 cells. The level of IL-17A in plasma was measured by Bioplex system, and its correlation with the percentage of IL-18 + Th17 cells was analyzed. Results:Compared with the healthy control group, the AR group showed increased ratios of CD4 + Th17 and IL-18 + Th17 cells ( P<0.01), decreased ratio of IL-18BPa + Th17 cells ( P<0.01), enhanced mean fluorescence intensity (MFI) of IL-18BPa ( P<0.01) and reduced MFI of IL-18Rα ( P<0.01); the nAR group showed enhanced MFI of IL-18BPa ( P<0.000 1) and reduced MFI of IL-18Rα ( P<0.000 1). The ratio of IL-18 + Th17 cells and the MFI of IL-18Rα in the AR group were higher than those in the nAR group ( P<0.05, P<0.01). House dust mite extract and Platanus pollen extract induced the expression of IL-18 and IL-18BPa by CD4 + Th17 cells of AR patients ( P<0.05). Moreover, house dust mite extract directly induced the CD4 + Th17 cells isolated from the healthy control subjects to express IL-18 and IL-18R ( P<0.05). Compared with healthy control subjects, AR patients had higher level of IL-17A in plasma and it was moderately correlated with the ratio of IL-18 + Th17 cells ( P<0.05). Conclusions:Allergens may be involved in the pathogenesis of AR by inducing blood CD4 + Th17 cells to express IL-18 and IL-18Rα.

BACKGROUND:In recent years,with the development of biological scaffold materials and bioprinting technology,tissue-engineered bone has become a research hotspot in bone defect repair. OBJECTIVE:To summarize the current treatment methods for bone defects,summarize the biomaterials and bioprinting technology for preparing tissue-engineered bone scaffolds,and explore the application of biomaterials and printing technology in tissue engineering and the current challenges. METHODS:Search terms were"bone defect,tissue engineering,biomaterials,3D printing technology,4D printing technology,bioprinting,biological scaffold,bone repair"in Chinese and English.Relevant documents published from January 1,2009 to December 1,2022 were retrieved on CNKI,PubMed and Web of Science databases.After being screened by the first author,high-quality references were added.A total of 93 articles were included for review. RESULTS AND CONCLUSION:The main treatment methods for bone defects include bone transplantation,membrane-guided regeneration,gene therapy,bone tissue engineering,etc.The best treatment method is still uncertain.Bone tissue engineering technology is a new technology for the treatment of bone defects.It has become the focus of current research by constructing three-dimensional structures that can promote the proliferation and differentiation of osteoblasts and enhance the ability of bone formation.Biological scaffold materials are diverse,with their characteristics,advantages and disadvantages.A single biological material cannot meet the demand for tissue-engineered bone for the scaffold.Usually,multiple materials are combined to complement each other,which is to meet the demand for mechanical properties while taking into account the biological properties of the scaffold.Bioprinting technology can adjust the pore of the scaffold,build a complex spatial structure,and is more conducive to cell adhesion,proliferation and differentiation.The emerging 4D printing technology introduces"time"as the fourth dimension to make the prepared scaffold dynamic.With the synchronous development of smart materials,4D printing technology provides the possibility of efficient repair of bone defects in the future.

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8⁺ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

Objective: To investigate the self-reported prevalence, clinical characteristics, complications of allergic rhinitis (AR) and the sensitization of outdoor air pollen allergens in children in the Inner mongolia grassland region. Methods: A multistage, stratified and random clustered sampling with a face-to-face interview survey study in children from 0 to 17 years old was performed together with 10 common allergen skin prick tests (SPT) and measurements of the daily pollen count in 6 regions in the Inner mongolia grassland region from May to August of 2015. SAS 9.4 software was used for data analysis. Results: A total of 2 443 subjects completed the study. The self-reported prevalence of AR was 26.6%. The prevalence of boys was higher than that of girls (28.8% vs 24.3%, χ²=6.157, P<0.05). Subjects from urban areas showed higher prevalence than rural areas (34.7% vs 18.8%, χ²=79.107, P<0.05). There was significant regional difference in the prevalence of AR among the six areas investigated (χ²=221.416, P<0.05). The main clinical symptoms of AR were sneezing (88.2%) and nasal congestion (78.6%). Among combined diseases, asthma accounted for 16.5% (107/650), rhinoconjunctivitis accounted for 47.9% (311/650). The peak season of AR was April and July, with the top SPT positive allergens of Artemisia species and chenopodium in this area. Conclusions The prevalence AR in children in the Inner mongolia grassland region is extremely high. Sneezing is the main clinical symptom. Rhinoconjunctivitis is the most common combined disease. High summer and autumn pollen exposure is the main cause of AR.

Considering that photodynamic therapy (PDT)-induced oxygen consumption and microvascular damage could exacerbate hypoxia to drive more glycolysis and angiogenesis, a novel approach to potentiate PDT and overcome the resistances of hypoxia is avidly needed. Herein, morpholine-modified PEGylated bilirubin was proposed to co-deliver chlorin e6, a photosensitizer, and diclofenac (Dc). In acidic milieu, the presence of morpholine could enable the nanocarriers to selectively accumulate in tumor cells, while PDT-generated reactive oxidative species (ROS) resulted in the collapse of bilirubin nanoparticles and rapid release of Dc. Combining with Dc showed a higher rate of apoptosis over PDT alone and simultaneously triggered a domino effect, including blocking the activity and expression of lactate dehydrogenase A (LDHA), interfering with lactate secretion, suppressing the activation of various angiogenic factors and thus obviating hypoxia-induced resistance-glycolysis and angiogenesis. In addition, inhibition of hypoxia-inducible factor-1α (HIF-1α) by Dc alleviated hypoxia-induced resistance. This study offered a sequentially responsive platform to achieve sufficient tumor enrichment, on-demand drug release and superior anti-tumor outcomes in vitro and in vivo.

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.