OBJECTIVE To investigate the effects of calcitriol on sepsis-induced immunosuppression and its potential mechanism. METHODS A sepsis-induced immunosuppression mice model was established using cecal ligation and puncture （CLP）. The 7-day survival rate， serum levels of tumor necrosis factor- α （TNF- α）， interleukin-6 （IL-6）， and IL-1β were determined in sham operation group， CLP group and calcitriol group （1 μg/kg）； the morphological changes of lung tissue in mice were observed. Lipopolysaccharide （LPS） tolerance macrophage models （representing sepsis-induced immunosuppression） were established using mice macrophage cell line RAW264.7 cells. The levels of TNF-α and IL-6 in cell supernatants as well as mRNA expressions of IL-1β， nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）， IL-18 and caspase-1 were assessed in culture medium group， LPS group， LPS tolerance group， and calcitriol （5 μmol/L） group. The following parameters were measured： propidium iodide （PI）-positive cell ratio， caspase-1 activity， lactate dehydrogenase （LDH） release， and Ca2+ levels. RESULTS Compared with CLP group， 7-day survival rate and serum levels of TNF-α， IL-6 and IL-1β were increased significantly in calcitriol group （P＜0.05）. Additionally， pulmonary tissue damage was markedly attenuated in calcitriol group. Compared with LPS tolerance group， the levels of TNF-α and IL-6 in cell supernatants， mRNA expressions of IL- 1β， NLRP3， IL-18 and caspase-1， PI-positive cell ratio， caspase-1 activity， LDH release， and Ca2+ levels were all increased significantly in calcitriol group （P＜0.05）. CONCLUSIONS Calcitriol can reverse sepsis-induced immunosuppression， and the mechanism of action may be E-mail：yarfwy@163.com achieved by the binding of calcitriol to vitamin D receptor，which promotes the release of Ca2+ from the endoplasmic reticulum， thereby driving the NLRP3/caspase-1-mediated pyroptosis pathway.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Tacrolimus is a commonly used medication for the treatment of nephrotic syndrome.Due to its narrow therapeutic window and significant pharmacokinetic differences among individuals,therapeutic drug monitoring is required during its clinical use.In the process of therapeutic drug monitoring,machine learning-based personalized dosing prediction models for tacrolimus can excavate medication patterns from a large amount of clinical data,assist in clinical decision-making,and achieve individualized precise medication.Machine learning models,the application progress of machine learning in personalized administration of tacrolimus for patients with nephrotic syndrome,modeling points of machine learning prediction models,and the limitations of current prediction models were reviewed in this paper,which could provide references for future research in this field.

Super-enhancers (SEs) are large clusters of enhancers located near the promoter and are necessary to determine the identity of cancer cells. The alterations of super-enhancers can cause dysregulation of the transcriptional program, which resulted in tumor cells being addicted to certain transcriptional programs. Tumor metastasis is the leading cause of death in cancer. Recently, SEs have been demonstrated to facilitate tumor metastasis by regulating lncRNA generation, tumor microenvironment, epithelial-mesenchymal transition, and cancer stem cells. In this review, the characteristics of SEs, the relationship between SEs and tumor metastasis, and inhibitors against SEs are summarized to provide a reference for the relevant mechanism of SEs regulating tumor metastasis and provide new perspectives for the diagnosis and treatment of patients with cancer metastasis.

Objective:To investigate the intention to participate in health care in transitional children and adolescents with diabetes and analyze its influencing factors.Methods:This was a cross-sectional survey study. From March to October 2021, 185 children and adolescents with diabetes were selected as research subjects by convenience sampling method from People′s Hospital Affiliated to Jiangsu University. General data questionnaire, Participation in Health Care Intention Questionnaire, Health Literacy Scale and Diabetes Self-management Scale were used to investigate, and multiple linear regression was used to analyze the influencing factors of the population′s intention to participate in health care.Results:The transitional children and adolescents with diabetes participation in health care intention total score was (124.87 ± 16.31) points, the health literacy total score was (33.70 ± 4.38) points, diabetes self-management total score was (35.11 ± 5.19) points. The regression analysis found that age, course of the disease, diabetes type, family structure modes, health literacy, and self-management ability were the main factors influencing adolescents involved in health care intention ( t values were -1.99-2.66, all P<0.05), including health literacy ability and disease management ability was positively correlated with the disease ( r = 0.250, 0.232, both P<0.01). Conclusions:The transitional children and adolenscents with diabetes have a medium level of intention to participate in health care. The transitional children and adolenscents with older age, longer disease course and nuclear family structure had higher levels of health care intention. The higher the level of health literacy and self-management, the higher the level of intention to participate in health care, medical staff should take targeted measures to improve the intention to participate in health care, promote this group to improve disease management ability and quality of life.

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.
Female ; Humans ; Pregnancy ; Blood Glucose/metabolism* ; Diabetes, Gestational/metabolism* ; Glucose/metabolism* ; Melatonin/metabolism* ; Polymorphism, Genetic ; PPAR gamma ; Receptor, Melatonin, MT2/genetics*

Objective To study the protective effect and related mechanism of pterostilbene(PTE)on renal ischemia-reperfusion injury(IRI)in mice.Methods Twenty-four C57 mice were randomly divided into 4 groups(n=6),including the sham operation group(S group),the renal ischemia reperfusion group(IR group),the renal ischemia reperfusion+5 mg/kg PTE group(IR+PTE1 group)and the renal ischemia reper-fusion+10 mg/kg PTE group(IR+PTE2 group).Hematoxylin-eosin(HE)and TUNEL staining were used to evaluate renal tissue injury.Creatinine(Cr),blood urea nitrogen(BUN),malondialdehyde(MDA)in renal tissue,inflammatory cytokines tumor necrosis factor(TNF-α),interleukin(IL)-1β and IL-6 levels in serum were detected with relevant kits.The expression of Bcl-2 interacting protein 3(BNIP3)and microtubule-asso-ciated protein light chain(LC)-3 Ⅱ in kidney tissue was detected by Western blot.Results Compared with the S group,serum levels of Cr,BUN,MDA,TNF-α,IL-1β and IL-6 in the IR group were increased,renal tu-bule injury score and apoptosis index were increased,and expressions of BNIP3 and LC-3 Ⅱ were down-regula-ted,with statistical significance(P＜0.05).Compared with the IR group,serum levels of Cr,BUN,MDA,TNF-α,IL-1β and IL-6 in the IR+PTE1 group were decreased,renal tubule injury score and apoptosis index were decreased,and expressions of BNIP3 and LC-3 Ⅱ were up-regulated,with statistical significance(P＜0.05).Compared with the IR+PTE1 group,serum levels of Cr,BUN,MDA,TNF-α,IL-1β and IL-6 in the IR+PTE2 group were decreased,renal tubule injury score and apoptosis index were decreased,and expres-sions of BNIP3 and LC-3 Ⅱ were up-regulated,with statistical significance(P＜0.05).Conclusion PTE has protective effect on renal IRI in mice.

Objective:To evaluate the feasibility and accuracy of a multi-dimensional peripheral quick contrast sensitivity function (pqCSF) measurement established based on Bayesian probability estimation algorithm.Methods:A cross-sectional study was conducted.Nineteen eyes of 12 healthy emmetropic subjects in Zhongshan Ophthalmic Center of Sun Yat-sen University from September 2017 to March 2018 were included, with an average age of (22.92±2.91) years.The average spherical power and cylindrical power were (-0.34±0.52)D and (-0.30±0.42)D, respectively, and the average uncorrected vision acuity was≥1.0.Based on the Bayesian probability algorithm, the peak contrast sensitivity γ max, the peak spatial frequency ? max, the bandwidth β and the low contrast intercept δ were used to quickly describe the contrast sensitivity function (CSF) curve of the full spatial frequency through multi-dimensional pqCSF method.The 16 peripheral visual field positions of all subjects were tested at 6°, 12°, 18° and 24° eccentricity of the superior, inferior, the temporal and nasal visual field by the pqCSF method, but the 18° eccentricity of temporal field, which was near the physiological blind spot, was excluded.The area under Log CSF (AULCSF) of different peripheral visual fields and the Log CSF of 19 spatial frequencies (distributed at equal intervals in logarithmic units) were compared.This study followed the Declaration of Helsinki, and the study protocol was approved by an Ethics Committee of Zhongshan Ophthalmic Center of Sun Yat-sen University (No.2018KYPJ017). Written informed consent was obtained from each subject prior to any examination. Results:With the increase of eccentricity in different visual fields, the AULCSF decreased gradually, and there were significant differences in AULCSF between different eccentricities (all at P<0.05). The AULCSF of the nasal and temporal visual field at 6°, 12° and 24° eccentricity was significantly larger than that of the superior and inferior visual field (all at P<0.05). As the distance from the fovea was increased, the pqCSF, the AULCSF, and the high-frequency cutoff were all decreased, and the standard deviation of AULCSF was increased gradually. Conclusions:The pqCSF method can depict a relatively complete peripheral CSF curve of a wide peripheral visual field, and reflect the function quality of the peripheral vision comprehensively and accurately.

OBJECTIVE: To explore the efficacy of individualized subcutaneous immunotherapy (SCIT) in allergic rhinitis(AR) maintain phase. METHOD: Compare nasal symptom scores (VAS) and special disease scale--nasal conjunctivitis quality of life questionnaire(RQLQ) score after 3 years treatment to evaluate the therapeutic effect of each group and the level of improving patients quality of life. Take patients' blood to detect the serum level of IL-10 by enzyme linked immunosorbent test (enzyme linked immunosorbent assay). RESULT: After 3 years treatment, there was no difference of VAS between the conventional SCIT group and the individualized SCIT group. ELISA results showed that the level of IL-10 was significantly higher in the drug symptomatic treatment group than that in the healthy group, the levels of IL-10 were significantly lower in the conventional SCIT group and the individualized SCIT group than that in the healthy group, but there was no difference between the conventional SCIT and the individualized SCIT group. CONCLUSION After 3 years treatment, there was no difference between conventional and individualized SCIT groups. But the efficacy of the conventional and individualized SCIT groups were significantly better than that in the drug symptomatic treatment group.
Desensitization, Immunologic ; Enzyme-Linked Immunosorbent Assay ; Humans ; Injections, Subcutaneous ; Interleukin-10 ; blood ; Precision Medicine ; Quality of Life ; Rhinitis, Allergic ; drug therapy ; Surveys and Questionnaires

OBJECTIVES: To explore the characteristics of nasal bone fracture caused by blunt instrument, including the fracture types, the fracture repair, and the difference of manifestations between X-ray and CT. To provide reference for the identification. METHODS: The information of basic situation, fracture site, injury manner, diagnosis method, expert opinion of 95 adult nasal fracture cases caused by blunt object, which occurred in Gutian county of Fujian province from January 1999 to December 2013, were analyzed by descriptive statistics. The identification conclusions of different injuries were compared according to new and old standards as well. RESULTS: There were total 95 adults including 87 male and 8 female. The fracture site and quantity have significant correlation with the nasal bone anatomical relations and the direction and size of the force. Compound fracture was most common. The fracture that could not be determined by X-ray could be clearly diagnosed by CT examination. According to new and old standards, different fracture types have different identification conclusions. CONCLUSIONS There are gender differences in nasal bone fracture cases. Larger external force is easy to cause compound fracture. CT examination is significantly better than X-ray examination.
Adult ; Female ; Humans ; Male ; Nasal Bone/injuries* ; Radiography ; Reference Standards ; Sex Factors ; Skull Fractures/diagnostic imaging* ; Tomography, X-Ray Computed