Study on the mechanism of magnesium calcium alloys/mineralized collagen composites mediating macrophage polarization to promote bone repair.

Magnesium-based composites are a focal point in biomaterials research. However, the rapid degradation rate of magnesium alloys does not align with the healing time of bone tissue. Additionally, the host reaction caused by magnesium implantation hampers its full osteogenic potential. To maintain an appropriate microenvironment, it is important to enhance both corrosion resistance and osteogenic activity of the magnesium matrix. In this study, a composite scaffold composed of mineralized collagen and magnesium alloy was utilized to investigate the regulatory effect of mineralized collagen on mouse macrophages and evaluate its impact on mouse bone marrow mesenchymal stem cells in terms of osteogenesis, immune response, and macrophage-induced osteogenic differentiation. This experiment examined the biocompatibility of mouse bone marrow mesenchymal stem cells and macrophage-induced osteogenic differentiation in vitro, and examined the expression levels of relevant pathways proteins. Magnesium calcium alloys/mineralized collagen exhibited extensive spreading, facilitated by broad and abundant pseudopodia that firmly adhered them to the material surface and promoted growth and pseudopodia formation. The findings revealed that magnesium calcium alloy/mineralized collagen scaffold materials induced osteogenic differentiation mainly through M2 polarization of macrophages. This effect was mainly mediated by promoting the integrin α2ß1-FAK-ERK1/2 signaling pathways and inhibiting the RANK signaling pathways.

Overexpression SPRY2 Suppresses Esophageal Squamous Cell Carcinoma Progression Via Inactivation of ERK/AKT Signaling / La Sobreexpresión SPRY2 Suprime la Evolución del Carcinoma de Células Escamosas de Esófago Mediante la Inactivación de la Señalización ERK/AKT

SUMMARY: Esophageal cancer is one of the most aggressive gastrointestinal cancers. Invasion and metastasis are the main causes of poor prognosis of esophageal cancer. SPRY2 has been reported to exert promoting effects in human cancers, which controls signal pathways including PI3K/AKT and MAPKs. However, the expression of SPRY2 in esophageal squamous cell carcinoma (ESCC) and its underlying mechanism remain unclear. In the present study, we aimed to investigate the detailed role of SPRY2 in the regulation of cell proliferation, invasion and ERK/AKT signaling pathway in ESCC. It was identified that the expression level of SPRY2 in ESCC was remarkably decreased compared with normal tissues, and it was related to clinicopathologic features and prognosis ESCC patients. The upregulation of SPRY2 expression notably inhibited the proliferation, migration and invasion of Eca-109 cells. In addition, the activity of ERK /AKT signaling was also suppressed by the SPRY2 upregulation in Eca-109 cells. Our study suggests that overexpression of SPRY2 suppress cancer cell proliferation and invasion of by through suppression of the ERK/AKT signaling pathways in ESCC. Therefore, SPRY2 may be a promising prognostic marker and therapeutic target for ESCC.

El cáncer de esófago es uno de los cánceres gastrointestinales más agresivos. La invasión y la metástasis son las principales causas de mal pronóstico del cáncer de esófago. Se ha informado que SPRY2 ejerce efectos promotores en los cánceres humanos, que controla las vías de señales, incluidas PI3K/AKT y MAPK. Sin embargo, la expresión de SPRY2 en el carcinoma de células escamosas de esófago (ESCC) y su mecanismo subyacente aún no están claros. En el presente estudio, nuestro objetivo fue investigar el papel detallado de SPRY2 en la regulación de la proliferación celular, la invasión y la vía de señalización ERK/AKT en ESCC. Se identificó que el nivel de expresión de SPRY2 en ESCC estaba notablemente disminuido en comparación con los tejidos normales, y estaba relacionado con las características clínico-patológicas y el pronóstico de los pacientes con ESCC. La regulación positiva de la expresión de SPRY2 inhibió notablemente la proliferación, migración e invasión de células Eca-109. Además, la actividad de la señalización de ERK/AKT también fue suprimida por la regulación positiva de SPRY2 en las células Eca-109. Nuestro estudio sugiere que la sobreexpresión de SPRY2 suprime la proliferación y la invasión de células cancerosas mediante la supresión de las vías de señalización ERK/AKT en ESCC. Por lo tanto, SPRY2 puede ser un marcador de pronóstico prometedor y un objetivo terapéutico para la ESCC.

Risk Factors for Pneumocystis jirovecii Pneumonia in Children With Systemic Lupus Erythematosus Exposed to Prolonged High-Dose Glucocorticoids.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic infection in immunocompromised children with systemic lupus erythematosus (SLE). Prophylaxis against PJP in high-risk children is crucial, but the risk factors for PJP in children with SLE are not adequately characterized. This study sought to identify the risk factors for PJP in long-term glucocorticoid-treated pediatric SLE patients. METHODS: This study encompassed 71 treatment episodes involving 64 children with prolonged (≥4 weeks) high-dose (≥20 mg/d prednisone) steroid regimens. Fourteen treatment episodes involved the PJP, whereas others did not. Risk factors for PJP were assessed through Cox regression. The predictive value of these factors was evaluated using receiver operating characteristic curves. The incidence of PJP in different risk groups was compared using the Kaplan-Meier method. RESULTS: The creatinine (hazard ratio, 1.009; 95% confidence interval [CI], 1.001-1.017; p = 0.021) and the lowest lymphocyte count (hazard ratio, 0.007; 95% CI, 0.000-0.373; p = 0.014) were independent risk factors for PJP in children with SLE. The receiver operating characteristic curve showed that using creatinine greater than 72.5 µmol/L and the lowest lymphocyte count less than 0.6 × 109/L as risk predictors for PJP resulted in an area under the curve value of 0.934 (95% CI, 0.870-0.997; p < 0.001). The study revealed a significant increase in PJP prevalence (p < 0.001) in children with elevated creatinine levels and low lymphocyte count. CONCLUSIONS: Elevated levels of creatinine and decreased lymphocyte count are identified as distinct risk factors for PJP in children with SLE who receive prolonged high-dose steroid therapy.

AQP3 Promotes the Invasion and Metastasis in Cervical Cancer by Regulating NOX4-derived H2O2 Activation of Syk/PI3K/Akt Signaling Axis.

Unrestrained chronic inflammation leads to the abnormal activity of NOX4 and the subsequent production of excessive hydrogen peroxide (H2O2). Excessive H2O2 signaling triggered by prolonged inflammation is thought to be one of the important reasons for the progression of some types of cancer including cervical cancer. Aquaporin 3 (AQP3) is a member of the water channel protein family, and it remains unknown whether AQP3 can regulate the transmembrane transport of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4)-derived H2O2 induced by the stimulation of inflammatory factors to facilitate the malignant progression in cervical cancer. In this study, cervical cancer HeLa cell line was respectively treated with diphenyleneiodonium (DPI), N-Acetylcysteine (NAC) or lentivirus-shRNA- AQP3. Plate cloning, cell migration or transwell invasion assays, etc. were performed to detect the invasive and migration ability of the cells. Western blot and CO-IP were used to analyze the mechanism of AQP3 regulating H2O2 conduction. Finally, in vivo assays were performed for validation in nude mice. AQP3 Knockdown, DPI or NAC treatments all reduced intracellular H2O2 influx, and the activation of Syk/PI3K/Akt signal axis was inhibited, the migration and invasive ability of the cells was attenuated. In vivo assays confirmed that the excessive H2O2 transport through AQP3 enhanced the infiltration and metastasis of cervical cancer. These results suggest that AQP3 activates H2O2/Syk/PI3K/Akt signaling axis through regulating NOX4-derived H2O2 transport to contribute to the progression of cervical cancer, and AQP3 may be a potential target for the clinical treatment of advanced cervical cancer.

Deletion in 1p36.33-p36.32 is associated with pancytopenia: a case report.

BACKGROUND: 1P36 deletion syndrome is recognized as the most common terminal microdeletion syndrome in humans, characterized by early developmental delay and consequent intellectual disability, seizure disorder, and distinctive facial features. Variable deletion locations may attributed to phenotypic variability. However, the abnormal phenotypes of hematology are rarely reported in 1P36 deletion syndrome patients. CASE PRESENTATION: We present a case of postnatal intellectual disability accompanied by pancytopenia. Copy number variation analysis revealed a pathogenic deletion in 1p36.331p36.32 with a deletion size of 2.21 Mb. Following successful treatment with glucocorticoids, the patient was diagnosed with immuno-related hemocytopenia (IRH). DISCUSSION: The patient experienced IRH, an uncommon characteristic of 1p36 deletion syndrome. The deletion fragment of 1p36.33-p36.32, particularly the loss of GNB1 gene, has been associated with the development of pancytopenia. Genotype-phenotype correlations are valuable in identifying the genes responsible for various clinical characteristics of the syndrome by associating phenotypic variation with specific genes located within the chromosome deletion region. Genome sequencing is recommended in cases where clinical manifestations indicate the presence of a genetic disorder but pose diagnostic challenges.

Exploring the pathogenesis and treatment of IgA nephropathy based on epigenetics.

IgA nephropathy is the most common primary glomerulonephritis worldwide. However, its exact cause remains unclear, with known genetic factors explaining only 11% of the variation. Recently, researchers have turned their attention to epigenetic abnormalities in immune-related diseases, recognizing their significance in IgA nephropathy's development and progression. This emerging field has revolutionized our understanding of epigenetics in IgA nephropathy research. Though in its early stages, studying IgA nephropathy's epigenetics holds promise for unraveling its pathogenesis and identifying new biomarkers and therapies. This review aims to comprehensively analyze epigenetics' role in IgA nephropathy's development and suggest avenues for potential therapeutic interventions. In the future, assessing and modulating epigenetics may become integral in diagnosing, tailoring treatments and assessing prognoses for IgA nephropathy.

Development and validation of a nomogram for predicting cefoperazone/sulbactam-induced hypoprothrombinaemia in Hospitalized adult patients.

Cefoperazone/sulbactam-induced hypoprothrombinaemia is associated with longer hospital stays and increased risk of death. The aim of this study was to develop and validate a nomogram for predicting the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia in hospitalized adult patients. This retrospective cohort study involved hospitalized adult patients at Xi'an Central Hospital from January 2020 to December 2022 based on the Chinese pharmacovigilance system developed and established by the Adverse Drug Reaction Monitoring Center in China. Independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were obtained using multivariate logistic regression and were used to develop and establish the nomogram. According to the same standard, the clinical data of hospitalized patients using cefoperazone/sulbactam at the Third Affiliated Hospital of Xi'an Medical University from January 1, 2023 to June 30, 2023 were collected as the external validation group. The 893 hospitalized patients included 95 who were diagnosed with cefoperazone/sulbactam-induced hypoprothrombinaemia. Our study enrolled 610 patients: 427 in the training group and 183 in the internal validation group. The independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were surgery (odds ratio [OR] = 5.279, 95% confidence interval [CI] = 2.597-10.729), baseline platelet count ≤50×109/L (OR = 2.492, 95% CI = 1.110-5.593), baseline hepatic dysfunction (OR = 12.362, 95% CI = 3.277-46.635), cumulative defined daily doses (OR = 1.162, 95% CI = 1.162-1.221) and nutritional risk (OR = 16.973, 95% CI = 7.339-39.254). The areas under the curve (AUC) of the receiver operating characteristic for the training and internal validation groups were 0.909 (95% CI = 0.875-0.943) and 0.888 (95% CI = 0.832-0.944), respectively. The Hosmer-Lemeshow tests yielded p = 0.475 and p = 0.742 for the training and internal validation groups, respectively, confirming the goodness of fit of the nomogram model. In the external validation group (n = 221), the nomogram was equally robust in cefoperazone/sulbactam-induced hypoprothrombinaemia (AUC = 0.837, 95%CI = 0.736-0.938). The nomogram model constructed in this study had good predictive performance and extrapolation, which can help clinicians to identify patients at high risk of cefoperazone/sulbactam-induced hypoprothrombinaemia early. This will be useful in preventing the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia and allowing timely intervention measures to be performed.

New insights from trio whole-exome sequencing in the children with kidney disease: A single-center retrospective cohort study.

BACKGROUND: Kidney disease of children markedly affects their health and development. Limited clinical data of early-stage kidney disease render a tremendous challenge for the accurate diagnosis. Trio whole-exome sequencing (Trio-WES) is emerging as a first-line diagnostic strategy in pediatric kidney disease, and shows important implications for the precision medicine strategies of children with kidney disease. METHODS: Trio-WES was performed in 133 Chinese children with kidney disease and their parents. The results for casual variants in genes known to cause kidney disease were analyzed. We further assessed the genetic diagnostic yield and the clinical implications of genetic testing. RESULTS: An overall diagnostic yield of 52.63% (70/133) was found, and the diagnostic rates ranged from 44.74% to 59.62% in different clinical phenotypes. The diagnostic yield of the three groups of simple proteinuria, renal insufficiency, and "other" was 50%, 50%, and 54.55%, respectively. Eight-seven diagnostic variants were identified in 70 probands with variants spanning 30 genes. The top 7 genes with diagnostic variants were COL4A5 (23, 26.44%), COL4A4 (13, 14.94%), ADCK4 (7, 8.05%), CLCN5 (3, 3.45%), ACE (3, 3.45%), PKD1 (3, 3.45%), and SLC12A3 (3, 3.45%), accounting for 63.22% of all variations in the cohort. CONCLUSIONS: The retrospective cohort study summarized the clinical utility of genetic testing in 133 probands, and expanded the phenotypic and genetic profiles of kidney disease in children. Trio-WES is an efficient diagnostic tool for children with kidney disease, which facilitates the clinical diagnosis and treatment. Our findings have important implications for the precise diagnosis of childhood nephropathy and may provide clinical guideline for disease management.

Epileptic convulsions probably induced by desloratadine: a case report.

Desloratadine, a second generation H1-antihistamine, is generally considered to be safe. We found only one article reporting four children with a family or disease history of epilepsy who developed the condition after desloratadine treatment, with all four patients recovering well. Here we describe a healthy boy who developed left-arm convulsions on day 68 after taking desloratadine, at which point the desloratadine treatment was immediately stopped. Investigations were completed on day 83 and the patient was diagnosed with epilepsy. He was prescribed sodium valproate combined with oxcarbazepine, topiramate, lamotrigine and clonazepam for 15 months, which did not control the convulsions. During the following 3 months the patient received sodium valproate combined with lacosamide, and on day 615 the seizures stopped and no further convulsions occurred. At the follow-up, his father reported that the boy's memory was not as good as it had been previously. The convulsions continued after the withdrawal of desloratadine; therefore, the pathological mechanism of convulsion and the treatment plan need further research.

Growth hormone treatment in pre-pubertal short Chinese children with chronic kidney disease prior to transplantation.

BACKGROUND: The effect of recombinant human GH (rhGH) in Chinese children with chronic kidney disease (CKD) is unclear. METHODS: This was a 52-week, multicenter, randomized, open-label, negative-controlled phase 3 study. Prepubertal subjects were randomized 1:1 to either daily subcutaneous injections of rhGH 0.05 mg/kg/day or no treatment for 52 weeks. RESULTS: A total of 68 subjects with a mean age of 7.8 ± 3.27 years were enrolled. At week 52, the height standard deviation score (HT-SDS) in the treated group increased by 0.75 ± 0.58, which was significantly higher compared with 0.17 ± 0.47 in the untreated group (least squares mean 0.58, 95% confidence interval, 0.32-0.84; P < 0.001). At week 52, significant improvements were observed in other growth parameters (height velocity [P < 0.001]), insulin-like growth factor 1 (IGF-1) SDS [P < 0.001], IFG-1/insulin-like growth factor binding protein-3 molar ratio [P < 0.001], and height [P < 0.001]) compared with the untreated control. Seven patients reported treatment-related adverse events (TRAEs) and most TRAEs were mild in severity. Most subjects recovered without further intervention. CONCLUSIONS: Daily rhGH for 52 weeks in children with CKD-induced growth retardation significantly improved HT-SDS and other growth parameters without compromising safety. IMPACT: The efficacy and safety of growth hormone (GH) therapy in Chinese children with chronic kidney disease (CKD) are unclear. This study found that giving short stature Chinese children with CKD daily recombinant human growth hormone (rhGH) for 52 weeks improved growth parameters without compromising safety. This study's information can give physicians the confidence to treat these patients in their clinical practice.

Combined treatment of marizomib and cisplatin modulates cervical cancer growth and invasion and enhances antitumor potential in vitro and in vivo.

Proteasome inhibition is an attractive approach for anticancer therapy. Cisplatin (cis-diamminedichloroplatinum, CDDP) is widely used as a standard chemotherapy drug in the treatment of solid malignant tumors, such as cervical cancer, ovarian cancer, colorectal cancer, and lung cancer. However, the development of CDDP resistance largely limits its clinical application. Proteasome inhibitors may enhance traditional chemotherapy agent-induced cytotoxicity and apoptosis. Marizomib (NPI-0052, salinosporamide A, Mzb), a second-generation proteasome inhibitor, shows synergistic anticancer activity with some drugs. Currently, the effect of Mzb on cervical cancer cell proliferation remains unclear. In this study, we explored the role of Mzb in three cervical cancer cell lines, HeLa, CaSki, and C33A, representing major molecular subtypes of cervical cancer and xenografts. We found that Mzb alone showed noteworthy cytotoxic effects, and its combination with CDDP resulted in more obvious cytotoxicity and apoptosis in cervical cancer cell lines and xenografts. In order to investigate the mechanism of this effect, we probed whether Mzb alone or in combination with CDDP had a better antitumor response by enhancing CDDP-induced angiopoietin 1 (Ang-1) expression and inhibiting the expression of TEK receptor tyrosine kinase (Tie-2) in the Ang-1/Tie-2 pathway, FMS-like tyrosine kinase 3 ligand (Flt-3L) and stem cell factor (SCF) as identified by a cytokine antibody chip test. The results suggest that Mzb has better antitumor effects on cervical cancer cells and can sensitize cervical cancer cells to CDDP treatment both in vitro and in vivo. Accordingly, we conclude that the combination of CDDP with Mzb produces synergistic anticancer activity and that Mzb may be a potential effective drug in combination therapy for cervical cancer patients.

Study on seafloor hydrothermal systems circulation flow and heat transfer characteristics.

In this work, the numerical simulation study of the hydrothermal flow and heat transfer process in the porous rock under 30 MPa pressure was developed. The flow and heat transfer characteristics of hydrothermal in rocks with different porosities are studied by changing the porosity of the rock. The simulation results show that the average flow velocity decreases and the average temperature increases when the porosity decreases. The velocity field and temperature field are coupled due to the nonlinear thermophysical properties of hydrothermal. The velocity field and temperature field have strongly interacted in the range of 400-450 ℃ and the effect of temperature on velocity is gradually diminishing outside the range. Most of the fluid will be "squeezed" into the crevice and the average velocity is almost three times the no-creviced case when a crevice is present. The existence of the crevice makes the total heat flux decrease from an overall perspective, and the crevice makes a large temperature gradient at the entrance and export of the crevice from a local perspective. These results provide theoretical support for the utilization of submarine hydrothermal fluid shallow circulation heat energy.

Regulation of Magnesium Matrix Composites Materials on Bone Immune Microenvironment and Osteogenic Mechanism.

Despite magnesium based metal materials are widely used in bone defect repair, there are still various deficiencies, and their properties need to be optimized. Composites synthesized with magnesium based metal as matrix are the research hotspot, and the host immune response after biomaterial implantation is very important for bone binding. By studying the immunoregulation of bone biomaterials, it can regulate the immune response in the process of osteogenesis and create a good local immune microenvironment, which is conducive to biomaterials to reduce inflammatory response and promote good bone binding. This article introduces the osteogenic mechanism of magnesium based metal materials and its regulation on bone immune microenvironment in detail.

Beliefs about medication and their association with adherence in Chinese patients with non-dialysis chronic kidney disease stages 3-5.

ABSTRACT: There is a scarcity of research into the impact of medication beliefs on adherence in patients with non-dialysis chronic kidney disease (CKD). This study is to determine the psychometric properties of the Chinese version of the Beliefs about Medicines Questionnaire (BMQ)-Specific among patients with non-dialysis CKD stages 3-5, and to assess the beliefs of CKD patients and their association with medication adherence.A cross-sectional study was conducted in CKD patients who recruited at the nephrology clinics of Xi'an Central Hospital, Xi'an, Shaanxi, China. The original BMQ-Specific was translated into Chinese. The internal consistency and test-retest reliability of the Chinese version of the BMQ-Specific scale were assessed, while exploratory and confirmatory factor analyses were also applied to determine its reliability and validity. The Kruskal-Wallis test and multiple ordered logistic regression were performed to identify the relationship between beliefs about and adherence to medication among CKD patients.This study recruited 248 patients. Cronbach's α values of the BMQ-Specific necessity and concern subscales were 0.826 and 0.820, respectively, with intraclass correlation coefficients of 0.784 and 0.732. Factor analysis showed that BMQ-Specific provided a good fit to the two-factor model. The adherence of patients was positively correlated with perceived necessity (r = 0.264, P < .001) and negatively correlated with concern (r = -0.294, P < .001). Medication adherence was significantly higher for the accepting group (high necessity and low concern scores) than for the ambivalent group (high necessity and concern scores; ß = -0.880, 95% confidence interval [CI] = -1.475 to -0.285), skeptical group (low necessity and high concern scores; ß = -2.620, 95% CI = -4.209 to -1.031) and indifferent group (low necessity and concern scores; ß = -0.918, 95% CI = -1.724 to -0.112).The Chinese version of BMQ-Specific exhibited satisfactory reliability and validity for use in patients with non-dialysis CKD stages 3-5 and has been demonstrated to be a reliable screening tool for clinicians to use to predict and identify the non-adherence behaviors of patients.

Risk factors for linezolid-induced thrombocytopenia in adult inpatients.

Background Previous reports about risk factors for linezolid-induced thrombocytopenia have been insufficient, often due to the variability in study design and population, and some factors have not yet been studied. Aim The aims of this study are to determine potential risk factors for linezolid-induced thrombocytopenia, and to analyze the influencing factors of different thrombocytopenia definitions. Method This retrospective study involved patients who were administered intravenous linezolid for ≥ 1 day between January 1, 2015 and January 1, 2021. Their demographic and clinical data were extracted from electronic medical records. Thrombocytopenia was defined as: ①thrombocytopenia with platelet count < 100 × 109/L and a decrease in 25% or more from baseline of the platelet count (criterion 1); ②thrombocytopenia due to a platelet count drop decrease of 25% or more from baseline (criterion 2). Risk factors were determined via binary logistic regression analysis. Results This study included 320 patients. Binary logistic regression analysis indicated that baseline platelet count (p < 0.001), linezolid therapy duration (p = 0.001) and shock (patients require vasoactive medications) (p = 0.019) were independent risk factors for criterion-1thrombocytopenia, while linezolid therapy duration (p < 0.001) and shock (p = 0.015) were independent risk factors for criterion-2 thrombocytopenia. There was also a significant correlation between shock and early-onset thrombocytopenia (p = 0.005 and 0.019 for criterion 1 and criterion 2, respectively). Conclusion Linezolid therapy duration and shock were common causes of different thrombocytopenia definitions; shock was correlated with early-onset thrombocytopenia. Platelet count should be monitored during linezolid therapy especially during long-duration therapy and in shock patients.

Differences in Manifestations and Gut Microbiota Composition Between Patients With Different Henoch-Schonlein Purpura Phenotypes.

Background: Gut microbiota plays an important role in the pathogenesis of immune-mediated diseases. However, the complex pathogenesis of Henoch-Schonlein Purpura (HSP) remains elusive. This study aimed to characterize the gut microbiota in HSP patients and explore the potential association between gut microbiota composition and phenotypic changes in HSP. Methods: 16SrRNA gene sequencing and bioinformatic analyses were performed using total DNA extracted from the fecal microbiota of 34 children with HSP, including 18 primary cases, 16 recurrent cases, and 23 healthy children. Results: The diversity indexes showed significant differences in the microbial community among the primary HSP groups, the recurrent HSP group and healthy controls. The abundance of Escherichia-Shigella in the recurrent HSP group was significantly higher than that in the primary HSP group, and the constructed ROC curve had an AUC value of 0.750. According to the Spearman correlation analysis, the abundance of Bacteroides was positively associated with the serum IgG level in children with HSP, while the abundance of Lachnoclostridium was negatively correlated with the complement component 3 (C3). The diversity indexes of gut microbiota in the HSP group with abdominal symptoms were higher than those in the HSP group without GI involvement, and also higher than those in the healthy control group. In the HSP group with GI involvement, the abundance of Faecalibacterium was decreased, while the abundance of Streptococcus and Fusobacteria was increased, compared to the HSP group without GI involvement. Conclusions: The gut microbiota of children with HSP was different from that of healthy children. The genus Escherichia-Shigella has a diagnostic value for HSP recurrence. Bacteroides and Lachnoclostridium may affect IgG and complement C3 levels in children with HSP. Abdominal symptoms in HSP children were related to gut microbiota (Streptococcus and butyric acid-producing bacteria).

Effect of magnesium ions/Type I collagen promote the biological behavior of osteoblasts and its mechanism.

Type I collagen (Col I) is a main component of extracellular matrix (ECM). Its safety, biocompatibility, hydrophilicity and pyrogen immunogenicity make it suitable for tissues engineering applications. Mg2+ also control a myriad of cellular processes, including the bone development by enhancing the attachment and differentiation of osteoblasts and accelerating mineralization to enhance bone healing. In our studies, Mg2+ bind collagen to promote the proliferation and differentiation of osteoblasts through the expression of integrins and downstream signaling pathways. In order to clarify the biological behavior effect of 10 mM Mg2+/Col I coating, we performed 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), alkaline phosphatase (ALP), 4'6-diamidino-2-phenylindole (DAPI), Alizarin red staining and Rhodamine B-isothiocyanate (RITC)-labeled phalloidin experiments and found that 10 mM Mg2+ group, Col I-coating group, 10 mM Mg2+/Col I-coating group, respectively, promoted the proliferation and differentiation of osteoblasts, especially 10 mM Mg2+/Col I-coating group. We detected the mRNA expression of osteogenic-related genes (Runx2, ALP and OCN, OPN and BMP-2) and the protein expression of signaling pathway (integrin α2, integrin ß1, FAK and ERK1/2), these results indicated that 10 mM Mg2+/Col I coating play an critical role in up-regulating the MC3T3-E1 cells activity. The potential mechanisms of this specific performance may be through activating via integrin α2ß1-FAK-ERK1/2 protein-coupled receptor pathway.

Assessment of direct oral anticoagulants administered as potentially inappropriate medications to elderly inpatients.

Background There is evidence that direct oral anticoagulants administered as potentially inappropriate medications increase the risk of bleeding and thromboembolic complications, which represent serious threats to human health. Objective To identify direct oral anticoagulants administered as potentially inappropriate medications for hospitalized patients aged ≥ 65 years in our hospital, and to determine associated factors and the correlation between potentially inappropriate medications and adverse reactions. Setting Xi'an Central Hospital, China. Method A retrospective cross-sectional study of elderly hospitalized patients who received either dabigatran or rivaroxaban at Xi'an Central Hospital between June 1, 2018 and June 1, 2019. The evaluation criteria of direct oral anticoagulants were formulated based on drug labels, disease guidelines and the 2019 American Geriatrics Society Beers Criteria, and any non-compliance with the criteria was considered to be potentially inappropriate medications. The Pearson chi-square test and a binary logistic regression model were used. Main outcome measure Factors associated with potentially inappropriate medications and correlation between potentially inappropriate medications and adverse reactions. Results This study analysed 315 patients aged ≥ 65 years. The application of our evaluation criteria identified 155 (49.2%) instances of potentially inappropriate medications, comprising 5 different types of potentially inappropriate medications. Fifteen adverse drug reactions occurred in the study participants. The Pearson chi-square test revealed significant differences in number of medications (p = 0.021) and creatinine clearance rate (p = 0.002) between potentially inappropriate medications and non-potentially inappropriate medications groups. In the binary logistic regression model, potentially inappropriate medications use was associated with creatinine clearance (creatinine clearance < 30: OR = 3.590, 95% CI = 1.214-10.615, p = 0.021), and there was no significant correlation between potentially inappropriate medications and adverse drug reactions after eliminating the confounding factors (age, length of hospitalization, number of disease combined) with p values of less than 0.25 (adjusted OR = 0.372, 95% CI = 0.117-1.182, p = 0.094). Conclusion This study revealed that the incidence of potentially inappropriate medications was relatively high, number of medications and creatinine clearance differed significantly between potentially inappropriate medications and non-potentially inappropriate medications groups, and potentially inappropriate medications was associated with creatinine clearance (creatinine clearance < 30 mL/min), but there was no significant correlation between potentially inappropriate medications and adverse drug reactions after eliminating the confounding factors.