A multi-omics analysis reveals vitamin D supplementation since childhood modulates molecules for signal transductions in the mouse striatum.

Vitamin D is a critical fat-soluble vitamin for the nervous system. Research suggests a potential link between vitamin D deficiency and attention-deficit hyperactivity disorder (ADHD), particularly in children and adolescents. The core symptoms of ADHD are associated with deficits in striatal functions, and maintaining sufficient levels of vitamin D may help prevent or alleviate ADHD symptoms. However, the molecular changes in the striatum caused by vitamin D supplementation that may contribute to the brain processes linked to ADHD symptoms remain unclear. In this study, we established a mouse model fed diets with three different dose gradients of vitamin D3 (0, 500, and 2000 IU/kg·day) from postnatal day 21 (P21) to 14 weeks of age. Striatal tissues from mice with gradient vitamin D3 intake were subjected to reduced representation bisulfite sequencing (RRBS), RNA-sequencing, and neurotransmitter profiling by liquid chromatography-mass spectrometry (LC-MS). Our findings indicate that vitamin D supplementation since childhood influenced the overall landscape of DNA methylations and the expression of many genes involved in critical neurological functions in a dose-dependent manner. Additionally, our data demonstrate how vitamin D modulated neuropeptide signaling pathways, as well as cholinergic and dopaminergic synapses in the striatum, through an orchestrated mechanism involving epigenetic and transcriptional regulations. Furthermore, we observed a synergistic effect of vitamin D on dopamine release following acute methylphenidate injection into our mouse model. In summary, this study provides mechanistic insights into how dietary vitamin D supplementation since childhood can modulate specific signal transductions among striatal cells, underscoring the importance of vitamin D supplementation for ADHD management.

[Diagnosis and treatment procedures and health management for patients with hereditary angioedema].

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.

[Preliminary insights into the practice of hypoallergenic home visiting program].

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.

Assembly of Ultralong Hydroxyapatite Nanowires into Enamel-like Materials.

To develop dental restorative materials with enamel-like structures, ultralong hydroxyapatite (HA) nanowires were synthesized by a hydrothermal method, followed by functionalization with 3-methacryloxypropyltrimethoxysilane (KH-570). The mixture of HA nanowires, KH-570, and light initiator was stirred and centrifuged. The precipitate was vacuum filtered to remove excessive KH-570 and then pressured under cold isostatic pressing (10 MPa × 24 h). Finally, the block was polymerized by lighting. Scanning electron microscopy and transmission electron microscopy showed that HA nanowires with aspect ratios >1,000 were assembled into enamel rod-like microstructures and evenly dispersed in the polymerized KH-570 silane matrix to form enamel-like structures. Thermogravimetric analysis demonstrated that the content of HA nanowires reached 72 wt% in the composite. The enamel-like composite showed a similar hardness, frictional property, and acid-etching property to those of enamel and a comparable or even better diametral tensile strength and compressive strength than some commercial composite resins in mechanical tests in vitro. In addition, the enamel-like composite had good cytocompatibility. Such enamel-like composites may have the potential to be used in biomimetic tooth restorations in the future.

Application of a non-target variable data independent workflow (vDIA) for the screening of prohibited substances in doping control testing.

A non-target variable Data Independent Acquisition (vDIA) workflow based on accurate mass measurements using a Q Exactive OrbiTrap is presented for the first time for equine doping control testing. The vDIA workflow uses a combination of MS1 events (1 to 2) and multiple vDIA events to cover the analytes of interest. The workflow basically captures a digital image of a sample allowing all relevant MS1 and MS2 data to be recorded. In theory, the workflow can accommodate an unlimited number of analytes as long as they are amenable to the sample extraction protocol and fall within the mass limits of the workflow. Additional targets fulfilling the above requirements can be added without changing any settings. The performance of the vDIA workflow was illustrated by applying it to two screening methods in horse urine, with one workflow covering 331 basic drugs and the other covering 45 quaternary ammonium drugs (QADs). Both screening methods have good detection sensitivity with 84% of the basic drugs having Limits of Detection (LoDs) of ≤ 1 ng/mL and 84% of the QADs having LoDs of ≤ 0.4 ng/mL. Other method characteristics including retention reproducibility, method precision and false hit rate will also be presented.

[A pilot study of transcranial alternating current stimulation in the treatment of drug-naive adult patients with major depressive disorder].

Objective: To explore the efficacy, adverse reactions, feasibility, and acceptability of transcranial alternating current stimulation (tACS) treating drug-naive adult patients with major depressive disorder (MDD), and provide basis for further study with a large sample. Methods: The study was performed in the Neuromodulation laboratory, Department of Neurology of Xuanwu Hospital, Capital Medical University (Beijing, China) from July, 2017 to June, 2018. Thirty Eligible first-episode MDD outpatients were randomized 1∶1 to receive active tACS or sham intervention. The tACS was administered in a 40 minute, 77.5 Hz frequency, 15 mA session with one forehead (Fp1, Fpz, and Fp2, in the 10/20 international placement system, 4.45 cm×9.53 cm) and two mastoid (3.18 cm×3.81 cm) stimulation for 20 times in 4 consecutive weeks at fixed day time frame once daily from Monday through Friday, with weekends off (week 4), followed by 4 weeks with no tACS treatment (week 8). By utilizing the Hamilton rating scale for depression-17 item (HRSD-17) to assess the depressive severity of MDD patients, adverse events were administered by the treatment-emergent adverse events, the Young mania rating scale, and the self-made common questionnaire on cranial electrical stimulation. The primary efficacy outcome was the remission rate defined as HRSD-17 score ≤7 at week 8. Secondary outcomes included the rates of remission at week 4 and response at weeks 4 and 8. Safety was assessed by evaluation of adverse events. Also the proportions of participants accepting the intervention and this study procedure were evaluated at weeks 4 and 8. Results: Thirty MDD patients completed the study, and both groups had no statistical differences on their demographic characteristics (P>0.05). At week 8, the active group had a remission rate of 10/15, which was higher than 3/15 in the sham group (P<0.05). Also, the remission rate (14/15) in the active group was higher than 5/15 of the sham group at week 4 (P<0.05). For the response rates, significant differences were found between groups at week 8. For safety, both groups showed no severe adverse events and no mania/hypomania. One participant per group had 2 times of tinnitus cerebri during the intervention days. All patients accepted the intervention and the study procedure. Conclusions: The pilot study indicated that tACS with 77.5 Hz and 15 mA may have a therapeutic effect on depressive symptoms. It is well-tolerated and safe, as well as feasible and acceptable for adults with MDD.

[Morphometric analysis program combined with magnetoencephalogram in the localization of epileptogenic foci in MRI-negative pharmacoresistant focal epilepsy patients].

Objective: To investigate the value of morphometric analysis program (MAP) combined with magnetoencephalogram (MEG) in the localization of epileptogenic foci in MRI-negative pharmacoresistant focal epilepsy (MNPFE) patients. Methods: A total of 42 consecutive MNPFE patients from Epilepsy center, Xuanwu Hospital, Capital Medical University from January 2015 to December 2016 were enrolled. The analysis process of MAP and magnetoencephalography (MEG) were performed independently. When the MAP+ region and the MEG+ region was in the same lobe, the MAP+ region was defined as the MAP+MEG+ region. The analysis results of MAP and MEG were used to do correlation analysis with surgical outcomes separately or simultaneously. Results: The positive rate of MAP was 69% (29/42), and the complete resection of MAP+ region was significantly associated with seizure-free outcome (P=0.027). The positive detection rate of MEG was 100% (42/42), and there was no significant association between the complete resection of MEG+ region and seizure-free outcome (P=0.517). The positive rate of MAP+MEG+ was 43% (18/42), and the complete resection of MAP+MEG+ region was significantly associated with seizure-free outcome (P=0.009). Conclusion: The combination of MAP which indicates subtle structural abnormalities and MEG which pictures electrophysiological features could probably achieve better epileptogenic foci localization in MNPFE patients.

[Clinical features and gene analysis of TBC1D24 gene mutation related early-onset focal myoclonic epilepsy].

Objective: To investigate the clinical features and genetic characteristics of patients with TBC1D24 gene mutation related early-onset focal myoclonic epilepsy. Methods: Clinical data of 3 patients with TBC1D24 gene mutation related early-onset focal myoclonic epilepsy of Xuanwu Hospital from November 2016 to June 2017 was collected and analyzed.Candidate gene mutations were screened by second generation sequencing. Results: Among the 3 patients, 1 was male and 2 were females.Seizure onset age was 4 months, 3 years and 5 years after birth respectively. Two patients had family history of epilepsy.They all had prolonged episodes of focal myoclonus. Two patients had mental retardation.Scalp electroencephalograms (EEG) was recorded in all 3 cases and myoclonic seizures were captured.The ictal EEGs were normal in all cases. In one patient, the ictal EEG of generalized seizure showed alpha rhythm originating from left fronto-central region. Brain magnetic resonance imaging (MRI) was normal in 2 patients. Abnormal signal was found bilaterally in cerebellum in 1 patient. The gene screening showed that two patients carried compound heterozygous mutation of TBC1D24 gene and one carried homozygous mutation, all of which were de novo mutations.All the patients were treated with multiple antiepileptic drugs (AEDs) and seizures were uncontrolled in 2 patients. One patient was followed up for 10 months without recurrence. Conclusions: TBC1D24 gene related early-onset focal myoclonic epilepsy is clinically characterized by early onset, prolonged focal myoclonus which relieved with sleep, mental retardation and poor response to AEDs.The interictal and ictal EEG usually show normal. Genetic analysis can assist in diagnosis and genetic counseling.

Safety and efficacy evaluation of laparoscopy in colorectal cancer with liver metastasis.

OBJECTIVE: To study the safety and efficacy of simultaneous completion of colorectal cancer resection and liver metastasis resection by total laparoscopy. PATIENTS AND METHODS: In the observation group, 40 patients with colorectal cancer combined with liver metastasis (CRCLM) were selected to receive total laparoscopic surgery. At the same time, 40 cases were selected for laparoscopic resection of colorectal cancer and hepatic resection as control group. RESULTS: The outcomes of the two methods in the treatment of CRCLM were compared. The results showed that the difference in surgery time between the two groups was not statistically significant (p>0.05). The blood loss, drainage tube retention time and anal exhaust recovery time in the observation group were significantly less than those in control group (p<0.05). No significant difference in completion rate was found between the two groups (p>0.05); the prevalence rate of complications in the observation group was significantly lower than that in control group (p<0.05). No significant differences in the median survival period and the survival rate at 1 year, 2 years and 3 years after surgery were found between the two groups (p>0.05). CONCLUSIONS: The outcomes of total laparoscopy in the treatment of CRCLM are not inferior to open surgery.

Interleukin-6 and interleukin-8 in diagnosing neonatal septicemia.

Neonatal septicemia (NS) is a common cause of death of newborn infants, hence early diagnosis and treatment are of the utmost importance. However, lack of specific clinical symptoms and late detection delay a correct diagnosis. It is therefore of great importance to establish auxiliary indexes for the early diagnosis of NS. To evaluate the value of interleukin (IL-6 and IL-8) in the diagnosis of NS, a prospective study was carried out. Seventy-five newborns who developed septicemia and received treatment in our hospital from January 2013 to December 2014 were selected as research subjects; also, 50 healthy newborns were set as a control group. The levels of serum IL-6 and IL-8 were compared between the two groups. Results demonstrated that levels of C-reactive protein (CRP), IL-6 and IL-8 of the septicemia group were higher than those of the control group on admission, although the difference had no statistical significance (P less than 0.05); the septicemia group had higher sequential organ failure assessment (SOFA) scores but lower pediatric critical illness scores (PCIS) compared to the control group (P less than 0.05); levels of CRP, IL-6 and IL-8 were in positive correlation to the SOFA scores and in negative correlation to PCIS. Analysis of receiver operating characteristics (ROC) curve demonstrated that the sensitivity, specificity and accuracy were 85.7%, 80.2% and 81.8%, respectively, when IL-6 level was set as 32 pg/mL, 78.1%, 64.2% and 66.9%, respectively when IL-8 level was set as 54 pg/mL, and 71.4%, 86.3% and 82.7% respectively, when detection of IL-6 and IL-8 were combined together. Hence it can be concluded that: IL-6 and IL-8 are involved in inflammatory reactions; levels of IL-6 and IL-8 were correlated to the severity of the infection; the value of IL-6 is higher than that of IL-8 in the diagnosis of neonatal septicemia and the combined detection of IL-6 and IL-8 can improve the accuracy of the diagnosis of neonatal septicemia.

Prognostic significance of serum sMICA levels in non-small cell lung cancer.

OBJECTIVE: The soluble form of major histocompatibility complex class I-related chain A (MICA) is released from the surface of tumor cells of epithelial origin. Serum levels of soluble MHC class I-related chain A (sMICA) is related with the prognosis of various types of cancer. However, there are studies on the prognostic value of sMICA in non-small cell carcinoma (NSCLC). In this study, we retrospectively investigated the relationship between sMICA levels and clinical features of NSCLC, and we assessed the prognostic value of sMICA in NSCLC. PATIENTS AND METHODS: sMICA levels were detected in 207 NSCLC patients and 207 normal control individuals with using enzyme-linked immunosorbent assay (ELISA), and its associations with clinicopathological parameters were evaluated. Survival curves were compared using the Kaplan-Meier method and log-rank tests. Univariate Cox regression was used on each clinical covariate to examine its influence on patient survival. Multivariate models were based on step-wise addition. RESULTS: Serum sMICA levels were significantly higher in NSCLC patients than in healthy controls (mean ± SD [pg/ml], 143.52 ± 27.6 vs. 32.4 ± 7.53 p < 0.01) and were significantly correlated with TNM stage, poorer differentiation, lymph node metastases and distant metastases. Survival analysis showed that a low sMICA level had longer survival time than those with high serum sMICA. Multivariate analyses indicated that high sMICA proved to be an independent predictor of survival time. CONCLUSIONS: Serum sMICA level in NSCLC patients is associated with metastasis. It is an indicator of a poorer survival probability. Serum sMICA levels may be an independent prognostic factor for NSCLC.

Association of vitamin D receptor BsmI gene polymorphism with risk of low bone mineral density in post-menopausal women: a meta-analysis.

The vitamin D receptor BsmI gene polymorphism is reportedly associated with low bone mineral density (BMD) in postmenopausal women, but results from previous studies are conflicting. In the present study, we investigated the association between this polymorphism and the risk of low BMD through a meta-analysis of published studies. A literature search of the Pubmed, Embase, and CNKI databases from inception through July 2013 was conducted. The meta-analysis was performed using the STATA 12.0 software. Crude odds ratios with 95% confidence intervals were used to assess the strength of any association. Eleven case-control studies were included for a total of 1468 low BMD cases and 2177 healthy controls. No significant variation in low BMD risk was detected in any of the genetic models. Further stratified analyses were performed to examine the effect of ethnicity. In the subgroup analysis, no significant association was found in Caucasians and in Asians. The meta-analysis results suggest that the BsmI polymorphism is not associated with low BMD risk in postmenopausal women.

Apoptosis induction by ultrasound and microbubble mediated drug delivery and gene therapy.

Apoptosis induction provides a promising strategy for tumor gene therapy. Non-invasive ultrasound is a novel non-virus transfer method. In the field of cancer therapy, it has been found that ultrasound alone or together with microbubble represents an appealing, efficient and novel technique, which could deliver therapeutic gene or drug to specific organs or tissues in a simple and noninvasive way. Moreover, apoptosis induction mediated by the novel ultrasound-targeted microbubble destruction technique is safer and more effective than other methods, inactivating tumor cells, restraining cell proliferation and improving therapeutic effects of gene or chemotherapeutic drugs. In this paper, we reviewed apoptosis induction by ultrasound and microbubble mediated drug delivery and gene therapy in vitro and in vivo.

Mass mortality of pond-reared Carassius gibelio caused by Myxobolus ampullicapsulatus in China.

From June to August 2009, allogynogenetic silver crucian carp Carassius gibelio (Bloch) pond-cultured at the Nanquan Experimental Station, China, were found to be heavily infected with myxosporeans, which caused mortalities ranging from 33% (13/40) to 90% (36/40) in the cages. The pharynxes of infected fish were swollen, nodular, and severely damaged. Based on morphological characters and 18S small subunit ribosomal DNA sequence similarity, the myxosporean was identified as Myxobolus ampullicapsulatus. This is the first report of M. ampullicapsulatus causing mass mortality of pond-reared C. gibelio.

Analysis of insulin signalling by RNAi-based gene silencing.

Using siRNA-mediated gene silencing in cultured adipocytes, we have dissected the insulin-signalling pathway leading to translocation of GLUT4 glucose transporters to the plasma membrane. RNAi (RNA interference)-based depletion of components in the putative TC10 pathway (CAP, CrkII and c-Cbl plus Cbl-b) or the phospholipase Cgamma pathway failed to diminish insulin signalling to GLUT4. Within the phosphoinositide 3-kinase pathway, loss of the 5'-phosphatidylinositol 3,4,5-trisphosphate phosphatase SHIP2 was also without effect, whereas depletion of the 3'-phosphatase PTEN significantly enhanced insulin action. Downstream of phosphatidylinositol 3,4,5-trisphosphate and PDK1, silencing the genes encoding the protein kinases Akt1/PKBalpha, or CISK(SGK3) or protein kinases Clambda/zeta had little or no effect, but loss of Akt2/PKBbeta significantly attenuated GLUT4 regulation by insulin. These results show that Akt2/PKBbeta is the key downstream intermediate within the phosphoinositide 3-kinase pathway linked to insulin action on GLUT4 in cultured adipocytes, whereas PTEN is a potent negative regulator of this pathway.

Endothelin-1 activates ET(A) receptors to increase intracellular calcium in model sensory neurons.

Endothelin-1 (ET-1) induces endothelin-A (ETA) receptor-mediated pain and selective excitation of nociceptors. Here we studied ET-1-induced changes in intracellular calcium (Ca2+in) in Fura-2 loaded mouse neuroblastoma-rat dorsal root ganglion hybrid cells (ND7/104). ET-1 (1-400 nM) induced concentration-dependent, transient increases in Ca2+in, probably of intracellular source. Responses to repeated application declined with increasing ET-1 concentration, implying receptor desensitization. Treatment of cells with the selective ETA receptor antagonist, BQ-123, produced a dose-dependent inhibition of the response that was 20% of ET-1 alone (IC50 = 20 nM, KI = 7 nM). No inhibition of the calcium response was observed with the selective ETB antagonist, BQ-788 (10-1000 nM). These results demonstrate that ET-1 induces dose- and ETA receptor-dependent release of Ca2+in in nociceptor-like neurons, and permit further examination of the pathways that underlie ET-1-induced pain signaling.

[Studies on metabolism of oxymatrine by human intestinal bacteria].

OBJECTIVE: To study the oxymatrine metabolism induced by human intestinal bacteria and its absorbed metabolites in blood. METHOD: TLC and HPLC were used to examine oxymatrine and its metabolites, and UV, IR, NMR and MS were used to confirm the chemical structures of the metabolites. RESULT: Oxymatrine was transformed into matrine by human intestinal bacteria metabolism in vitro. Rats were given orally oxymatrine 100 mg.kg-1 and were decapitated 3 hours after administration, and their blood was taken to examine serum metabolites by TLC and HPLC, which revealed that oxymatrine and matrine were absorbed into blood. CONCLUSION: Oxymatrine will be transformed into matrine when it is given orally and both of the alkaloids can be absorbed to blood.