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.

[Summary]Early-onset DM and suboptimal glycemic control leads to irreversible damage to nerves,blood vessels,and other target organs.Vitamin D is an important calcium and phosphorus regulator in the body,and its receptor is present in various cells throughout the body,playing an integral role in many biological effects.Previous studies have identified an inverse or independent relationship between vitamin D levels and the prevalence of microangiopathic complications in patients with type 2 diabetes mellitus(T2DM).However,it remains to be investigated whether serum vitamin D levels have a contributory role in the development of microvascular complications in patients with early-onset T2DM,and whether supplementation with vitamin D has a beneficial impact on the risk of microvascular complications in early-onset T2DM.In this article,we will review the advances in the relationship between vitamin D and early-onset T2DM combined with microangiopathy.

[Summary]Early-onset DM and suboptimal glycemic control leads to irreversible damage to nerves,blood vessels,and other target organs.Vitamin D is an important calcium and phosphorus regulator in the body,and its receptor is present in various cells throughout the body,playing an integral role in many biological effects.Previous studies have identified an inverse or independent relationship between vitamin D levels and the prevalence of microangiopathic complications in patients with type 2 diabetes mellitus(T2DM).However,it remains to be investigated whether serum vitamin D levels have a contributory role in the development of microvascular complications in patients with early-onset T2DM,and whether supplementation with vitamin D has a beneficial impact on the risk of microvascular complications in early-onset T2DM.In this article,we will review the advances in the relationship between vitamin D and early-onset T2DM combined with microangiopathy.

Objective To investigate the risk factors of drug resistance in patients with ischemic stroke by clopidogrel therapy and provide references for promoting clinical individualized drug therapy. Methods A total of 202 inpatients diagnosed with ischemic stroke were admitted and given dual anti-treatment (aspirin+clopidogrel). CYP2C19 genotype was detected by microarray hybridization during hospitalization, and CYP2C19 gene polymorphisms were classified into fast metabolism group, medium metabolism group and slow metabolism group according to the type of drug metabolism. Patients were tested for platelet inhibition induced by adenosine diphosphate (ADP) according to thromboelastographic (TEG) on 7~14 d of drug administration. ADP <30% was classified as clopidogrel drug resistance group and ADP ≥30% as non-resistance group. Logistic regression analysis was used to study the risk factors for the development of clopidogrel resistance. Results Among 202 patients with ischemic stroke, 87 were in the resistant group and 115 in the non-resistant group. The proportion of patients with clopidogrel resistance combined with diabetes and the level of white blood cell count were higher than that in the non-resistant group, and the differences were statistically significant (P<0.05).The proportion of patients with clopidogrel resistance in the CYP2C19 intermediate metabolism group was significantly higher than that in the fast metabolism group, and the rate of platelet inhibition was also significantly lower than that in the fast metabolism group, all with statistically significant differences (P<0.05). Conclusion Combined diabetes mellitus, high white blood cell count levels and CYP2C19 mid-metabolic phenotype are independent risk factors for the development of clopidogrel resistance in patients with ischemic stroke.

Objective To evaluate the second catalog of the key monitoring and rational use drugs(KMRUD),and to provide a reference framework for medical institutions to develop their own KMRUD catalogs and management policies.Methods A comprehensive search on official websites of national and provincial health administrative departments was conducted using the keywords"key monitoring","rational drug use",and"the second catalog".Announced catalogs and related policy documents pertaining to KMRUD use were collected and systematically organized.Comparative analyses were performed between the national KMRUD catalogs of the first and second batches,as well as between the second batch of provincial KMRUD catalogs and the national standard.Additionally,the adoption and variation of national KMRUD drug management policies across provinces,as well as the uniformity and divergence of provincial KMRUD management policies,were examined.Results The second national KMRUD catalog maintained 7 drug varieties from the first batch,eliminated 13,and introduced 23 new varieties.Of the 24 surveyed provinces,9 modified their provincial catalogs relative to the national second batch KMRUD catalog,resulting in alterations to 66 drug varieties within 10 Anatomical Therapeutic Chemical(ATC)classes,primarily systemic anti-infectives.Several provinces,including Xinjiang,Inner Mongolia,Liaoning,Shanghai,and Qinghai,implemented additional management measures such as the establishment of clinical application guidelines and the clarification of application conditions and principles.Moreover,provinces like Inner Mongolia,Shandong,Jilin,and Heilongjiang expanded their KMRUD management toolbox by developing drug monitoring indicators.The revision of inclusion rules from the first to the second KMRUD catalog has led to the incorporation of numerous essential clinical drugs.The prior protocol of medical institutions excluding drugs unilaterally is no longer viable,as it may disrupt the standard medication supply,potentially raising treatment costs.Conclusion Medical institutions ought to assimilate the updated implications of KMRUD use,draw on established provincial monitoring and management methodologies,enhance clinical application guidelines,and articulate conditions and principles for clinical use.Furthermore,by employing prescription review mechanisms,in-hospital monitoring,evaluation,and advanced warning systems,medical institutions can strategically oversee KMRUD use.

Maintaining the stemness of the transplanted stem cell spheroids in an inflammatory microenvironment is challenging but important in regenerative medicine. Direct delivery of stem cells to repair periodontal defects may yield suboptimal effects due to the complexity of the periodontal inflammatory environment. Herein, stem cell spheroid is encapsulated by interfacial assembly of metal-phenolic network (MPN) nanofilm to form a stem cell microsphere capsule. Specifically, periodontal ligament stem cells (PDLSCs) spheroid was coated with Fe^III/tannic acid coordination network to obtain spheroid@[Fe^III-TA] microcapsules. The formed biodegradable MPN biointerface acted as a cytoprotective barrier and exhibited antioxidative, antibacterial and anti-inflammatory activities, effectively remodeling the inflammatory microenvironment and maintaining the stemness of PDLSCs. The stem cell microencapsulation proposed in this study can be applied to multiple stem cells with various functional metal ion/polyphenol coordination, providing a simple yet efficient delivery strategy for stem cell stemness maintenance in an inflammatory environment toward a better therapeutic outcome.
Anti-Bacterial Agents/pharmacology* ; Capsules/pharmacology* ; Cell Differentiation ; Cell Encapsulation ; Cells, Cultured ; Ferric Compounds/pharmacology* ; Osteogenesis/physiology* ; Periodontal Ligament ; Polyphenols/pharmacology* ; Stem Cells ; Tannins/pharmacology*

Objective With methods of literature review, item test, reliability and validity test, etc., to develop a fall risk assessment scale specific to the obstetrical department, which, after reliability and validity test, can be used for women health care before, at and after delivery.Methods Items in the fall risk assessment scale for pregnant and maternal women were determined and weights were assigned by reviewing relative risk factors in literature, referring to items in other fall risk assessment tools from home and aboard. After a preliminary scale was formed, 154 pregnant and maternal women hospitalized from May to December 2016 were assessed, so that reliability and validity of the scale were tested.Results In this fall risk assessment scale for the obstetrical department, test-retest reliability was 0.822, interrater reliability was 0.926, content validity of expertise was 0.927, and area under the curve (ROC) was 0.750 (P<0.05). When the dividing value was 3.5, sum of sensitivity (0.714) and specificity (0.714) reached the max.Conclusions The new fall risk scale, with favorable reliability and validity, can filter patients with high risk of fall, yet, it is still to be testified and perfected in future application.

Objective To explore the effect of quality control circle ( QCC) activities on increasing early neonatal contact rate of mother and early breast sucking rate .Methods Set up a QCC,then follow the steps of QCC with professional tools to solve existing problems in early skin-to-skin contact for mothers and their healthy newborn infants and early breast sucking .Rate was compared before and after the improvements .Results The early neonatal contact rate of mother and early breast sucking rate increased from 80.94% to 93.57%,and the difference was significant (χ2 =35.07,P<0.001).Conclusions The application of the quality improvement tool of QCC could improve the early skin-to-skin contact for mothers and their healthy newborn infants and early breast sucking , and helps the mother to breastfeed successfully .

OBJECTIVETo investigate the mechanisms underlying the ability ofheparin-treated dendritic cells (DCs) to promote Th0 to Th1 differentiation in chronic hepatitis B (CHB).

METHODSPeripheral blood mononuclear cells (PBMCs) were isolated from CHB patients and cultured in RPMI-1640 with recombinant GM-CSF and IL-4 with or without heparin to obtain DCs for study. The levels of Toll-like receptors (TLRs) on the DCs were measured using FACS and qPCR techniques.DC subsets with high expression of TLRs were selected for analysis of functional changes by treatment with the corresponding TLR-siRNA. The CD4+ T cell subpopulation was purified from peripheral blood by Dynal immunomagnetic beads, and then the production of IL-12 by DCs in the presence of poly(I:C) or R848 and ofIFN and IL-4 by Th cells co-cultured with DCs was evaluated by ELISA. The t-test was used for statistical analysis.

RESULTSTLR3 expression, and not expression of TLR 7 or TLR8,was significantly increased in heparin-treated DCs as compared to levels detected in the DCs without heparin treatment (t =2.849,P less than 0.05;t =3.027,P less than 0.05). The level of IL-12 produced by heparin-treated DCs stimulated with poly(I:C) was obviously higher than that produced by DCs without heparin treatment and stimulated with poly(I: C) (t =8.68,P less than 0.01) or with R848 (t =19.01,P less than 0.01). However, the IL-12 production by TLR3-siRNA transfected-DCs was significantly reduced (t =31.49, P less than 0.01).When Th cells from allogenic patients with CHB were co-cultured with the TLR3-siRNA transfectedDCs, the frequency ofCD4+ IFN+ cells was significantly reduced (1.64+/-0.57% vs.6.31+/-0.88%,P less than 0.01),as was the capability of Thl to generate IFNg (t =20.83,Pless than 0.01).

CONCLUSIONHeparin may have up-regulated the TLR3 expression level of DCs, and sequentially promoted Th0 to Th1 differentiation.

CD4-Positive T-Lymphocytes ; cytology ; Cell Differentiation ; Coculture Techniques ; Dendritic Cells ; cytology ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Heparin ; pharmacology ; Hepatitis B, Chronic ; immunology ; Humans ; Interferon-gamma ; metabolism ; Interleukin-12 ; metabolism ; Interleukin-4 ; pharmacology ; Monocytes ; cytology ; Recombinant Proteins ; pharmacology ; Toll-Like Receptor 3 ; metabolism

OBJECTIVE:To investigate the effect of clinical pharmacist intervention on prophylactic application of antibiotics in cardiothoracic surgery. METHODS:Medical records of patients underwent cardiothoracic surgery were collected from our hospi-tal during Mar. to Apr. in 2014 (before intervention) and during Jun. to Jul. in 2014 (after intervention). Those were divided into pre-intervention group(n=115)and post-intervention group(n=119). The prophylactic application effect of antibiotics was com-pared before and after intervention. RESULTS:After intervention,the rates of prophylactic application were decreased significantly from 96.5% to 72.3%;the rationality rate of antibiotics selection was improved significantly from 27.9% to 94.2%;The course of prophylactic medication decreased significantly from(5.4±2.8)days to(2.3±1.8)days;the difference had statistical significance before and after intervention(P<0.01). The postoperative infection rate was decreased from 13.0% to 5.9%,the difference had no statistical significance(P=0.074). The average hospitalization time,average drug costs,and average hospitalization expenses were decreased significantly,the difference had statistical significance(P<0.05 or P<0.01). CONCLUSIONS:Clinical pharmacist inter-vention to prophylactic application of antibiotics in cardiothoracic surgery can control the infection effective and guarantee reason-able and safe use of drugs during perioperative period.