Effects of dietary astaxanthin supplementation on growth performance, antioxidant status, immune response, and intestinal health of rainbow trout (Oncorhynchus mykiss).

A feeding trial was conducted to assess the impacts of dietary astaxanthin from wall-broken Haematococcus pluvialis (WBHPA) on the growth performance, antioxidant status, immune response, and intestinal health of rainbow trout (Oncorhynchus mykiss). Six experimental diets were formulated with various concentrations of WBHPA, ranging from 0 to 8.4 g/kg (containing 0 to 125 mg/kg astaxanthin). Each diet was fed to triplicate groups of rainbow trout (mean initial weight of 561 g) twice daily for 9 consecutive weeks. The survival rate and feed intake of fish exhibited no significant differences among the dietary groups (P > 0.05). Similarly, dietary inclusion of 25 to 100 mg/kg astaxanthin did not significantly affect the weight gain and daily growth coefficient (P > 0.05), but excessive inclusion of astaxanthin (125 mg/kg) slightly depressed these parameters (P < 0.05). Dietary inclusion of 25 to 50 mg/kg astaxanthin increased the activities of intestinal digestion and absorption enzymes (lipase, creatine kinase, and alkaline phosphatase), while the inclusion of 25 to 75 mg/kg astaxanthin improved the immune response of fish. Furthermore, regardless of inclusion level (25 to 125 mg/kg), dietary astaxanthin supplementation strengthened the intestinal mucosal barrier function and improved antioxidant activity, thereby promoting intestinal development. Conclusively, 25 to 75 mg/kg astaxanthin from WBHPA was recommended to be included in diets for rainbow trout.

Case report: Successful treatment of advanced colon cancer in an eighty-year-old man with long-term and multi-stage endoscopic minimally invasive therapy.

Background: No previous studies have reported on the use of minimally invasive endoscopic therapy for colon cancer in older patients. Case presentation: An 80-year-old man was admitted to our hospital with haematochezia and diagnosed with advanced colon cancer in 2018. Traditional surgical care was rejected by his family. We successfully treated the patient with multiple minimally invasive endoscopic therapies, such as argon plasma coagulation, from 2018 to 2021. Conclusion: Invasive endoscopic therapy is a feasible way to treat colon cancer in older patients.

Optimizing Anesthetic Practices for Mud Crab: A Comparative Study of Clove Oil, MS-222, Ethanol, and Magnesium Chloride.

Anesthesia serves as an effective method to mitigate the stress response in aquatic animals during aquaculture and product transportation. In this study, we assessed the anesthetic efficacy of clove oil, tricaine methane-sulfonate (MS-222), ethanol, and magnesium chloride by anesthesia duration, recovery time, 24-hour survival rate, and the behavior of mud crabs (Scylla paramamosain). Additionally, the optimal anesthetic concentration for varying body weights of mud crabs was also investigated. The results revealed that clove oil emerged as the optimal anesthetic for mud crabs, with a 24-hour survival rate surpassing those observed in MS-222 and magnesium chloride treatments. Ethanol caused amputation and hyperactivity in mud crabs. Regression analyses between the optimal anesthetic concentration of clove oil and the weight categories of 0.03-27.50 g and 27.50-399.73 g for mud crabs yielded the following equations: y = 0.0036 x3 - 0.1629 x2 + 1.7314 x + 4.085 (R2 = 0.7115) and y = 0.0437 x + 2.9461 (R2 = 0.9549). Clove oil exhibited no significant impact on serum cortisol, glucose, lactate content, aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities, or superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels in mud crabs across different treatment groups. Anesthesia induced by clove oil in mud crabs resulted in an increase in inhibitory neurotransmitters such as glycine. However, the recovery from anesthesia was associated with elevated levels of the excitatory neurotransmitters L-aspartic acid and glutamate. In conclusion, clove oil proves to be a safe and optimal anesthetic agent for mud crabs, exerting no physiological stress on the species.

A Potential Immune-Related miRNAs Regulatory Network and Corresponding Diagnostic Efficacy in Schizophrenia.

PURPOSE: Immune-related pathways actively participate in the progression of schizophrenia (SCZ), however, roles of immune-related miRNAs in SCZ are still unclear. METHODS: A microarray expression study was conducted to explored roles of immune-related genes in SCZ. Functional enrichment analysis by using "clusterProfiler" was used to identify molecular alterations of SCZ. Protein-protein interaction (PPI) network was constructed and helped core molecular factors identification. Based on The Cancer Genome Atlas (TCGA) database, clinical significances of hub immune-related genes in cancers were also been explored. Then, correlation analyses were used to determine immune-related miRNAs. We further validated that hsa-miR-1299 could be an effective diagnostic biomarker for SCZ via analyzing multi-cohorts' data and quantitative real-time PCR (qRT-PCR). RESULTS: A total of 455 mRNAs and 70 miRNAs that were differentially expressed between SCZ and control samples. Functional enrichment analysis based on differentially expressed genes (DEGs) hinted that immune-related pathways were significantly correlated with SCZ. Furthermore, a total of 35 immune-related genes that involved in disease onset and showed significant co-expressed relationships. Hub immune-related gene CCL4 and CCL22 are valuable in tumor diagnosis and survival prediction. Furthermore, we also identified 22 immune-related miRNAs that play important roles in this disease. An immune-related miRNAs-mRNAs regulatory network was constructed to provide miRNAs regulatory roles in SCZ. Core miRNAs expression status of hsa-miR-1299 were also validated in another cohort, which suggested its diagnostic performance for SCZ. CONCLUSIONS: Our study reports the downregulation of some miRNAs in the process of SCZ are important. Shared genomics characteristics between SCZ and cancers also provide novel insights for cancers. A significant alteration of hsa-miR-1299 expression is effective as biomarker for the diagnosis of SCZ, suggesting that this miRNA could be a specific biomarker.

CircFOXP1 alleviates brain injury after acute ischemic stroke by regulating STAT3/apoptotic signaling.

According to previous studies, circular RNAs (circRNAs) are involved in multiple pathological processes of acute ischemic stroke (AIS). However, the relationship between circFOXP1 and IS has not yet been reported. Here, we found that circFOXP1 expression was significantly decreased in the peripheral blood of AIS patients compared to controls and was associated with the severity and prognosis of AIS. Functionally, knockdown and overexpression of circFOXP1 promoted and inhibited apoptotic signaling, respectively, following oxygen-glucose deprivation/reperfusion (OGD/R) treatment in vitro. Adeno-associated virus (AAV)-mediated circFOXP1 overexpression attenuated neurological deficits and improved functional recovery after transient middle cerebral artery occlusion (tMCAO) treatment in vivo. Mechanistically, decreased QKI expression inhibited circFOXP1 biogenesis under hypoxic conditions. Decreased circFOXP1 expression accelerated signal transducer and activator of transcription 3 (STAT3) protein degradation by binding to and increasing STAT3 protein ubiquitination, ultimately aggravating brain injury after cerebral ischemia by activating apoptotic signaling. In summary, our study is the first to reveal that circFOXP1 alleviates brain injury after cerebral ischemia by regulating STAT3/apoptotic signaling, which provides a potentially novel therapeutic target for AIS.

Sensitizing Tumors to Immune Checkpoint Blockage via STING Agonists Delivered by Tumor-Penetrating Neutrophil Cytopharmaceuticals.

Immune checkpoint inhibitors (ICIs) have displayed potential efficacy in triple-negative breast cancer (TNBC) treatment, while only a minority of patients benefit from ICI therapy currently. Although activation of the innate immune stimulator of interferon genes (STING) pathway potentiates antitumor immunity and thus sensitizes tumors to ICIs, the efficient tumor penetration of STING agonists remains critically challenging. Herein, we prepare a tumor-penetrating neotype neutrophil cytopharmaceutical (NEs@STING-Mal-NP) with liposomal STING agonists conjugating on the surface of neutrophils, which is different from the typical neutrophil cytopharmaceutical that loads drugs inside the neutrophils. We show NEs@STING-Mal-NP that inherit the merits of neutrophils including proactive tumor vascular extravasation and tissue penetration significantly boost the tumor penetration of STING agonists. Moreover, the backpacked liposomal STING agonists can be released in response to hyaluronidase rich in the tumor environment, leading to enhanced uptake by tumor-infiltrating immune cells and tumor cells. Thus, NEs@STING-Mal-NP effectively activate the STING pathway and reinvigorate the tumor environment through converting macrophages and neutrophils to antitumor phenotypes, promoting the maturation of dendritic cells, and enhancing the infiltration and tumoricidal ability of T cells. Specifically, this cytopharmaceutical displays a significant inhibition on tumor growth and prolongs the survival of TNBC-bearing mice when combined with ICIs. We demonstrate that neutrophils serve as promising vehicles for delivering STING agonists throughout solid tumors and the developed neutrophil cytopharmaceuticals with backpacked STING agonists exhibit huge potential in boosting the immunotherapy of ICIs.

Comprehensive Analysis of Blood-Based m6A Methylation in Human Ischemic Stroke.

Alterations of N6-methyladenosine (m6A) methylation have been reported in the cerebral cortices of mouse and rat models of ischemic stroke (IS). However, the role of m6A methylation in human IS is still unknown. We assessed m6A levels in peripheral blood from patients with IS and healthy controls. A transient middle cerebral artery occlusion and reperfusion (tMCAO/R) mouse model, and an oxygen-glucose deprivation/reperfusion (OGD/R) model in A172 cells were established to further assess m6A levels. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing were performed in the peripheral blood of patients with IS and healthy controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to identify underlying biological processes. In this study, we found that global m6A levels were elevated in the peripheral blood of patients with IS, in the cerebral cortex of mice after tMCAO/R treatment and in A172 cells after OGD/R treatment. MeRIP-seq analysis identified 2115 altered m6A peaks in patients with IS, 1052 upregulated and 1063 downregulated. Downregulated methylated mRNAs were enriched in Hippo signaling pathway, cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, etc. Upregulated methylated mRNAs were enriched in calcium signaling pathways, Hedgehog signaling pathway, MAPK signaling pathway, etc. Moreover, a total of 84 differentially expressed mRNAs with altered m6A peaks were identified and enriched in EGFR tyrosine kinase inhibitor, Hematopoietic cell lineage, and cytokine-cytokine receptor interactions. This study is the first to profile the transcriptome-wide m6A methylome of peripheral blood in human IS and uncover increased global m6A levels in the peripheral blood of patients with IS.

Intervention mechanism of self-degradation of ready-to-eat sea cucumber by adding green tea extract and gallic acid.

Gallic acid (GA) and green tea extract (GT) could retard the self-degradation of ready-to-eat sea cucumber (RSC). The physical and chemical properties of RSC were changed after cross-linking. Cross-linkers could retard the conversion of α-helix like structure to random coil. Besides, the peptides of cross-linked RSC were easily broken at the sites of G, E, A, L, S, H, Y, V and I after stored for 30 d. The self-degradation rate of RSC before and after cross-linking was determined by synthetic typical peptides. After cross-linked by GA, the relative peak heights of NQ, NL and GLQ increased by 20.59%, 11.14% and 31.49%, indicating that GA could effectively retard the degradation of the peptides during storage. Moreover, hydrogen bond was confirmed as the main force to maintain the stability of RSC body wall before and after cross-linking.

Gastroduodenal intussusception caused by gastric gastrointestinal stromal tumor in adults: a case report and literature review.

Intussusception mostly occurs in childhood and is rare in adults. Although intussusception can occur in any part of the gastrointestinal tract, gastroduodenal intussusception caused by a gastric tumor is relatively uncommon in clinical practice. A PubMed search identified 24 published cases of gastroduodenal intussusception caused by gastric gastrointestinal stromal tumor (GIST); however, it is possible that we missed other cases not included in PubMed. Here we report a case of gastroduodenal intussusception caused by gastric GIST in an 85-year-old man. He came to the hospital because of recurrent black stools. Plain computed tomography (CT) scan indicated a mass in the gastric antrum, with slight enhancement in the arterial phase on enhanced CT scan. He was diagnosed with GIST. In addition, images indicated that the mass overlapped into the duodenum, and gastroduodenal intussusception was thus considered. Gastroscopy showed a huge mass in the gastric body. According to the gastroscopy and CT results, gastroduodenal intussusception caused by a gastric tumor was considered. The patient underwent complete surgical removal, which revealed a mass originating from the gastric antrum and overlapping into the duodenum. The postoperative pathological diagnosis was intermediate-risk gastric GIST. The patient was followed up for 4 months without tumor recurrence.

CircUSP36 attenuates ischemic stroke injury through the miR-139-3p/SMAD3/Bcl2 signal axis.

Circular RNAs (circRNAs) play important roles in a variety of physiological and pathological processes. Researches demonstrated that circRNAs provided novel strategies for the prevention and treatment of IS. However, the biological function of hsa_circ_0045932 (circUSP36) has not been revealed yet. Here, we explored the effect of circUSP36 on IS and its mechanism. In the present study, we found that circUSP36 expression was significantly decreased in the peripheral blood of IS patients and was negatively correlated with the severity, infarct volume and poor prognosis of IS. Functionally, circUSP36 silencing inhibited cellular activity and proliferation and promoted apoptosis after oxygen-glucose deprivation/reperfusion (OGD/R) treatment, while circUSP36 overexpression reversed these cellular phenotypes in vitro. Adeno-associated virus (AAV)-mediated overexpression of circUSP36 attenuates brain injury and neurological deficit and promotes motor function recovery of transient middle cerebral artery occlusion (tMCAO) mice. Subsequently, the RNA antisense purification (RAP) and luciferase reporter assay confirmed that circUSP36 acts as a sponge to adsorb miR-139-3p, and miR-139-3p could bind and inhibit SMAD3 expression. Further rescue experiments showed that both miR-139-3p overexpression and SMAD3 silencing could abolish the antiapoptotic effect of circUSP36. In summary, we reveal for the first time that circUSP36 attenuates ischemic stroke injury through the miR-139-3p/SMAD3/Bcl2 signal axis, which make circUSP36 a potential therapeutic target for IS.

The NSUN5-FTH1/FTL pathway mediates ferroptosis in bone marrow-derived mesenchymal stem cells.

Ferroptosis is a type of cell death induced by the iron-dependent accumulation of lipid hydroperoxides and reactive oxygen species (ROS) in cells. Inhibiting ferroptosis is important for improving the survival of transplanted bone marrow-derived mesenchymal stem cells (BMSCs). Although it is known that NOP2/Sun RNA methyltransferase 5 (NSUN5) post-transcriptionally regulates ferroptosis in BMSCs through RNA methylation, the precise mechanisms underlying these effects have not been reported. In this study, we demonstrate that NSUN5 is downregulated in erastin-induced ferroptosis in BMSCs. Ferroptosis was inhibited by the overexpression of NSUN5 or ferritin heavy chain/light-chain (FTH1/FTL) and was enhanced by NSUN5 knockdown. RNA immunoprecipitation experiments revealed that NSUN5 binds to FTH1/FTL, while NSUN5 depletion reduced the levels of 5-methylcytosine in FTH1/FTL RNA and increased intracellular iron concentrations, resulting in the downregulation of glutathione peroxidase 4 (GPX4) and the accumulation of ROS and lipid peroxidation products. Co-immunoprecipitation experiments demonstrated that the recognition of FTH1 and FTL by NSUN5 is dependent on the recruitment of tumor necrosis factor receptor-associated protein 1 (TRAP1). These results suggested that the NSUN5-FTH1/FTL pathway mediates ferroptosis in BMSCs and that the therapeutic targeting of components of this pathway may promote resistance to ferroptosis and improve the survival of transplanted BMSCs.

Analysis of expression profiles and bioinformatics suggests that plasma exosomal circular RNAs may be involved in ischemic stroke in the Chinese Han population.

Circular RNAs (circRNAs) have been confirmed to be associated with ischemic stroke(IS), but the involvement of exosomal circRNAs in plasma still needs to be extensively discussed. Therefore, we aimed to investigate the expression profile of exosomal circRNAs in plasma and the potential roles and mechanisms of exosomal circRNAs in the pathogenesis of ischemic stroke in the Chinese Han population. In this study, the plasma exosomal circRNA expression profiles of three IS patients and three healthy controls were analyzed using circRNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and circRNA-miRNA-mRNA regulatory network analysis were performed for the aberrantly expressed genes. Protein-protein interaction (PPI) networks and molecular complex detection algorithms (MCODEs) were analyzed by STRING and Cystoscope for functional annotation and construction, respectively. RNA-Seq analysis revealed that a total of 3540 circRNAs were aberrantly expressed in exosomes, 1177 circRNAs were significantly upregulated, and 2363 circRNAs were downregulated in IS patients compared to healthy controls. Bioinformatics analysis revealed that the parental genes of differentially expressed circRNAs as well as the mRNAs predicted in the circRNA-miRNA-mRNA regulatory network are enriched for signaling pathways associated with IS pathology, such as the MAPK signaling pathway, lipid and atherosclerosis, neurotrophic factor signaling pathways, mTOR signaling pathway, the p53 signaling pathway etc. Then, 10 hub genes were identified from the PPI and module networks, including FBXW11, FBXW7, UBE2V2, ANAPC7, CDC27, UBC, CDC5L, POLR2H, POLR2F and RBX1. Overall, the present study provides evidence of an altered plasma exosomal circRNA expression profile and its potential function in IS. Our findings may contribute to the study of the pathogenesis of circRNAs in IS and provide ideas for studying potential diagnostic biomarkers and therapeutic targets for IS.

Transformation of iopamidol and atrazine by peroxymonosulfate under catalysis of a composite iron corrosion product (Fe/Fe3O4): Electron transfer, active species and reaction pathways.

Cast iron pipes are commonly applied in drinking water distribution systems (DWDSs); peroxymonosulfate (PMS) is a promising alternative for drinking water disinfection; organic micropollutants is still present in drinking water after waterworks' treatment. However, iron corrosion products may affect the reactions between a disinfectant and organic micropollutants. The study investigated the transformation of iopamidol (IPM) and atrazine (ATZ) by PMS under the catalysis of a composite iron corrosion product (Fe/Fe3O4). The pseudo-first-order rate constants (k) for the degradation of IPM and ATZ were 1.47 and 1.03 min-1, respectively. Electron paramagnetic resonance (EPR) experiments indicated that PMS was effectively activated to yield sulfate radical (SO4•-) and hydroxyl radical (HO•), mainly via the reduction by Fe component, dissolved Fe2+ and generated Feocta2+. SO4•- contributed more than HO• to the degradation of IPM and ATZ, and the radical yield achieved 0.97 mol/mol. The k values reached maximum with Fe/Fe3O4 and PMS doses of 2.5 g L-1 and 25 mg L-1, respectively. The optimum mass fraction of Fe3O4 in Fe/Fe3O4 (MFmag) and pH were 10% and 7.0, respectively. The k values increased with increasing temperature, while decreased in the presence of water matrix. Most of the iodine released from IPM was oxidized to IO3-, and NH4+ was the dominant species of nitrogen released from ATZ. The identification of transformation intermediates showed that the radical chain reactions of IPM was mainly initiated from single electron transfer and radical adduct formation, while those of ATZ was primarily initiated from hydrogen atom abstraction and radical adduct formation.

Combination of metabolic intervention and T cell therapy enhances solid tumor immunotherapy.

Treatment of solid tumors with T cell therapy has yielded limited therapeutic benefits to date. Although T cell therapy in combination with proinflammatory cytokines or immune checkpoints inhibitors has demonstrated preclinical and clinical successes in a subset of solid tumors, unsatisfactory results and severe toxicities necessitate the development of effective and safe combinatorial strategies. Here, the liposomal avasimibe (a metabolism-modulating drug) was clicked onto the T cell surface by lipid insertion without disturbing the physiological functions of the T cell. Avasimibe could be restrained on the T cell surface during circulation and extravasation and locally released to increase the concentration of cholesterol in the T cell membrane, which induced rapid T cell receptor clustering and sustained T cell activation. Treatment with surface anchor-engineered T cells, including mouse T cell receptor transgenic CD8+ T cells or human chimeric antigen receptor T cells, resulted in superior antitumor efficacy in mouse models of melanoma and glioblastoma. Glioblastoma was completely eradicated in three of the five mice receiving surface anchor-engineered chimeric antigen receptor T cells, whereas mice in other treatment groups survived no more than 64 days. Moreover, the administration of engineered T cells showed no obvious systemic side effects. These cell-surface anchor-engineered T cells hold translational potential because of their simple generation and their safety profile.

Phosphoinositide-3-kinase regulatory subunit 1 gene polymorphisms are associated with schizophrenia and bipolar disorder in the Han Chinese population.

Schizophrenia (SCZ) and bipolar disorder (BD) are severe psychiatric disorders that share many genetic risk factors. This study aimed to investigate the association of phosphoinositide-3-kinase regulatory subunit1 (PIK3R1) gene rs3756668 and rs3730089 polymorphisms with SCZ and BD risks and determine the expression levels of PIK3R1. A total of 548 SCZ cases, 512 BD cases, and 598 healthy controls were included in this study. Single nucleotide polymorphisms (SNPs) were genotyped using the Sequenom MassARRAY platform, and quantitative reverse transcription polymerase chain reaction was conducted to examine the mRNA expression of PIK3R1. The genotypic distribution of rs3756668 in the BD group was significantly different from that in the healthy controls (P = 0.038). After adjustment for gender and age was made, rs3730089 was significantly associated with the risk of SCZ [AA/(AG + GG): OR = 2.25, Padj = 0.040; AA/GG: OR = 2.27, Padj = 0.038]. The SNP rs3756668 was associated with the susceptibility of BD (AA+GG/AG: OR = 0.73, P = 0.011) and the association remained after adjusting for gender and age. The mRNA level of PIK3R1 was significantly upregulated in patients with BD compared with that in the control group (P < 0.001). In terms of the diagnostic value of PIK3R1 for BD, the receiver operating characteristic curve analysis showed an area under the curve of 0.809 with 74.0% sensitivity and 73.9% specificity. PIK3R1 may be the shared susceptibility gene of SCZ and BD and may be a potential diagnostic biomarker for BD.

TP53 Polymorphism Contributes to the Susceptibility to Bipolar Disorder but Not to Schizophrenia in the Chinese Han Population.

TP53 has been reported to be involved in diverse neurological processes related to the pathogenesis of psychosis. In this study, we aim to determine the association of TP53 polymorphisms, rs1042522 and rs17879353, with the susceptibility to schizophrenia (SCZ) or bipolar disorder (BD) in Chinese Han population. A total of 548 SCZ patients, 512 BD patients, and 598 healthy controls were recruited. Genotyping was conducted through Sequenom MassARRAY technology platform. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect TP53 expression level. Results revealed that the allele frequency and genotype distribution of rs1042522 within BD patients were significantly different from those of the controls. Rs1042522 was significantly associated with BD risk under diverse genetic models. However, no significant association was found for rs17879353 and BD risk and for rs1042522 and rs17879353 and SCZ risk. TP53 expression was significantly increased in SCZ patients and BD patients compared with that in the controls but was significantly decreased in BD patients with CC genotype of rs1042522 compared with that in other BD patients with either CG or GG genotype. In summary, we observed for the first time that rs1042522 is significantly associated with BD risk in the Chinese Han population. The increased TP53 expression might affect the occurrence of BD and SCZ, and rs1042522 might affect the progress of BD by disturbing gene expression.

Further Developments of the Phenyl-Pyrrolyl Pentane Series of Nonsteroidal Vitamin D Receptor Modulators as Anticancer Agents.

The vitamin D3 receptor (VDR), which belongs to the nuclear-receptor superfamily, is a potential molecular target for anticancer-drug discovery. In this study, a series of nonsteroidal vitamin D mimics with phenyl-pyrrolyl pentane skeletons with therapeutic potentials in cancer treatment were synthesized. Among them, 11b and 11g were identified as the most effective agents in reducing the viability of four cancer-cell lines, particularly those of breast-cancer cells, with IC50 values in the submicromolar-concentration range. In addition, 11b and 11g possessed VDR-binding affinities and displayed significant partial VDR-agonistic activities determined by dual-luciferase-reporter assays and human-leukemia-cell-line (HL-60)-differentiation assays. Furthermore, 11b and 11g inhibited tumor growth in an orthotopic breast-tumor model via inhibition of cell proliferation and induction of cell apoptosis. More importantly, 11b and 11g exhibited favorable pharmacokinetic behavior in vivo and did not increase serum calcium levels or cause any other apparent side effects. In summary, 11b and 11g act as novel VDR modulators and may be promising candidates for cancer chemotherapy.

Lumbar sympathectomy reduces vascular permeability, possibly through decreased adenosine receptor A2a expression in the hind plantar skin of rats.

BACKGROUND: The effect of lumbar sympathectomy for the treatment of lower limb ischemia remains a matter of controversy. METHODS: Sprague-Dawley rats were subjected to lumbar sympathectomy, after which Evans blue dye was injected into the hind plantar skin. Extravasation of dye was measured and compared with rats undergoing sham operation. Hind plantar skin was processed for HE staining, immunohistochemistry, and Western blot. RESULTS: In sympathectomized rats, blue stained areas in hind plantar skin and concentrations of Evans blue were significantly less than that of sham sympathectomy (control) rats, both 2 weeks and 3 months after surgery. Expression of prostaglandin E2, bradykinin, bradykinin B2 receptor, and adenosine triphosphate were not significantly different between the sympathectomized and control groups. Adenosine receptor A2a expression was significantly reduced in the sympathectomized group both 2 weeks and 3 months after surgery. CONCLUSION: Vascular permeability in the hind plantar skin of rats decreases following lumbar sympathectomy, possibly via reduced expression of adenosine receptor A2a.

Value of history taking in children and adolescents with cardiac syncope.

AIM: This study was designed to investigate the value of history taking in identifying children with cardiac syncope, and to improve diagnostic efficiency and accuracy in children with cardiac syncope. METHODS AND RESULTS: We compared the characteristics of a group of children and adolescents with cardiac syncope at the Pediatric Syncope Unit of five hospitals in China with those with typical vasovagal syncope. We included a cohort of 275 patients in Pediatric Syncope Unit. A cardiac cause of syncope was established in 31 patients, autonomic-mediated reflex syncope in 214, non-syncopal attacks in 15, and in the remaining 15 the cause of syncope remained unexplained. Cardiac syncope was triggered by exercise, whereas vasovagal syncope by prolonged standing, warm-crowded place, and fear or pain emotion. Syncopal spells occurred at various positions in cardiac syncope. Children who had prodromal symptoms with cardiac syncope were significantly fewer than those with vasovagal syncope. Most children with cardiac syncope had history of abnormal electrocardiogram findings when compared with children suffering from vasovagal syncope. On multivariable analysis, history of abnormal electrocardiogram findings and exercise-triggered syncope were independent predictors of cardiac syncope. CONCLUSION: Children and adolescents with a history of abnormal electrocardiogram findings and exercise-related syncope spells were at high risk for cardiac syncope.

[A modified Calgary syncope syndrome score in the differential diagnosis between cardiac syncope and vasovagal syncope].

OBJECTIVE: This study aimed at analyzing the usefulness of a modified Calgary Syncope Syndrome Score in the differential diagnosis between cardiac syncope (CS) and vasovagal syncope (VVS) in children through a large sample clinical study. METHOD: Totally 189 children [112 males, 77 females, aged 2 - 18 yrs, mean age (12.4 ± 3.1) yrs] with CS and VVS who were at the syncope clinic or admitted to the Department of Pediatrics, Peking University First Hospital from August 2002 to April 2011 were included in the study. The diagnosis was analyzed by a modified Calgary Syncope Syndrome Score and receiver operating characteristic (ROC) curve was used to explore the predictive value of different Calgary Syncope Syndrome Scores in differential diagnosis between CS and VVS. RESULT: There were significant differences in the score between CS [-5.00(-7, 1)] and VVS [1(-4, 6)] (P < 0.01). When the score was ≤ -2.5, the sensitivity and specificity of the differential diagnosis between CS and VVS were 95.4% and 67.7%, respectively. Since the modified Calgary Syncope Syndrome Score was integer number, CS should be considered when the score was less than -3. CONCLUSION: The modified Calgary Syncope Syndrome Score might be used as an initial diagnostic method in differential diagnosis between CS and VVS, based on the history of the patients.