[Application of artificial intelligence in prevention and control of COVID-19 in Guangzhou city].

Since the outbreak of COVID-19, it has spread rapidly throughout the country and even in the world. As a first tier city, Guangzhou is also the South Gate of China, with large population mobility and severe and complex prevention and control situation. Guangzhou CDC, together with Tencent and Alibaba Cloud, has made full use of its artificial intelligence technology to carry out a series of practices in case transmission chain analysis, close contact and other key personnel management, front-line staff prevention and control skills training and convenience services. Through the application of artificial intelligence in different scenarios, the difficulties and challenges in the prevention and control are solved, and the speed of epidemic prevention and control is increased.

[Clinical, myopathological and genetic features of two Chinese families with paramyotonia congenita].

Objective: To investigate the clinical, myopathological and genetic mutation characteristics in two Chinese families with paramyotonia congenita (PMC). Methods: Clinical manifestations, electrophysiology, muscle pathology and gene sequencing of two Chinese families with PMC were analyzed retrospectively. Results: Family 1 involved 12 patients in 4 consecutive generations and family 2 involved only 1 patient in 3 generations. The onset of symptoms in all patients started at early childhood. Both probands presented with myotonia triggered by cold and paroxysmal weakness. However, the other 11 patients in family 1 only manifested cold-induced myotonia. Serum creatine kinase (CK) was slightly elevated between attacks of weakness in the 2 probands, and was even greater than 10 000 U/L during the episodes of weakness in the second proband, whose lower limb MRI revealed edema in bilateral medial gastrocnemius. Electromyography showed diffuse myotonia discharge and myogenic impairment in both probands, and myotonia discharge in the first proband's mother. Muscle pathology of both probands showed mild myopathic changes, and tube aggregation was occasionally observed in the second one. Genetic testing revealed a maternally inherited heterozygous R1448H mutation of SCN4A gene in the first proband and part of his family. A novel heterozygous R1448G mutation of SCN4A gene was reported in the second proband. Conclusions: Cold-triggered myotonia with or without paroxysmal weakness are the common characteristics of PMC. Myotonic potential and myogenic impairment can be tested in electromyography. The p.R1448G mutation is a new missense mutation.

[Contagiousness and secondary attack rate of 2019 novel coronavirus based on cluster epidemics of COVID-19 in Guangzhou].

Objective: To analyze the contagiousness and secondary attack rate of 2019 novel coronavirus in cluster epidemics in Guangzhou and provide evidence for the prevention and control of COVID-19. Methods: All the individuals identified to be infected with 2019-nCoV in Guangzhou, including confirmed cases and asymptomatic cases, were included and classified as imported cases and local cases. The first case of each cluster epidemic was defined as index case, and the number of subsequent infections was calculated to evaluate the contagiousness and secondary attack rate of 2019 novel coronavirus in the shortest incubation period of 1-3 days. Results: As of 18 February, 2020, a total of 349 cases of 2019-nCoV infection, including 339 confirmed cases (97.13%) and 10 asymptomatic cases (2.87%) were reported in Guangzhou. There were 68 clusters involving 217 2019-nCoV infection cases (210 confirmed cases and 7 asymptomatic cases). The median number of subsequent infections caused by an index case in a cluster epidemic was 3, among which 2 were confirmed cases and 1 was asymptomatic cases, respectively. The average number of contagiousness was 2.18 in shorted incubation period of 1-3 days (The average number of infected cases were 2.18 cases by the index case in a cluster epidemic), the average infection number in family members was 1.86, and the infection ratio of family member transmission was 85.32% (1.86/2.18). The secondary attack rate in close contacts with shortest incubation period of 1-3 days was 17.12%-18.99%, the secondary attack rate in family members was 46.11%-49.56%. Conclusions: The cluster epidemic of COVID-19 in Guangzhou mainly occurred in families, the contagiousness was high. It is necessary to strengthen the prevention and control to reduce the community transmission of COVID-19.

Cine magnetic resonance urography for postoperative evaluation of reconstructive urinary tract after ileal ureter substitution: initial experience.

AIM: To report the initial experiences with functional cine magnetic resonance urography (cine MRU) and assess its usefulness as a novel postoperative evaluation method of ileal ureter substitution. MATERIALS AND METHODS: The medical records of 17 patients from who underwent cine MRU during June 2010 to December 2019 during their follow-up after ileal ureter substitution were collected. The cine MRU videos of reconstructive urinary tract were observed, and the luminal diameter, contraction ratio, peristaltic waves, and ureteral jets were measured. RESULTS: Seventeen patients underwent cine MRU after ileal ureter substitution during their follow-up. Based on their cine MRU videos assessing the morphology and the peristaltic motility of the reconstructive urinary tract, there was resolution of preoperative hydronephrosis, which matched their ameliorative renal function. Clearly, peristaltic motility of the ileal graft was observed in 14 patients with obvious peristaltic waves and ureteral jets. CONCLUSION: This study is the first to assess the clinical utility of functional cine MRU during the patient follow-up after ileal ureter substitution. Cine MRU is a radiation-free, non-invasive imaging method that can clearly show the morphology and the peristaltic motility of the ileal graft. Therefore, cine MRU, as a novel technique, will be extremely useful in the postoperative evaluation of patients after ileal ureter substitution.

[Correlation of orexin-2 receptor gene polymorphisms with Alzheimer's disease].

Objective: To investigate the association between orexin-2 receptor (OX2R) gene polymorphisms and Alzheimer's disease (AD). Methods: A total of 350 patients with AD diagnosed at the People's Hospital of Zhengzhou University from January 2014 to January 2018 were enrolled as the case group, and 350 healthy subjects were selected as the control group, and their general demographic data were collected. The peripheral blood samples were collected for DNA extraction, and the polymorphisms of 6 loci in OX2R gene in the two groups were detected by polymerase chain reaction (PCR) and gene sequencing. The differences in genotype and gene frequency distribution between the two groups were compared. Results: The genotype distribution of OX2R gene rs2653349 and rs2292041 in the case group was significantly different from that in the control group (P<0.05). Multivariate Logistic regression analysis showed that rs2653349(GA+AA) genotype was an independent risk factor for AD(P=0.009). Five haplotypes were found in the haplotype analysis, and there were differences between the case group and the control group: rs2653349+rs2292041 GA type(χ(2)=10.922, P=0.000 1), rs2653349+rs2292041+ rs3122169 GAA type (χ(2)=8.687, P=0.003), ATC type(χ(2)=8.329, P=0.003 9), rs2653349+ rs2292041 AT type(χ(2)=6.504, P=0.010 8), rs2653349+rs2292041+rs3122169 ATA type(χ(2)=17.511, P=0.000 1). Conclusion: The OX2R gene rs2653349 and rs2292041 polymorphisms in the Han population of Henan may be associated with AD, and the A allele may be a susceptible factor for AD.

[Skeletal muscle MRI of lower limbs in patients with facioscapulohumeral dystrophy].

Objective: To investigate MRI features of lower limbs in patients with facioscapulohumeral dystrophy(FSHD). Methods: The clinical manifestations, myopathological findings and MRI images of 5 FSHD patients were studied retrospectively from June 2016 to December 2017 at Department of Neurology, Henan Provincial People's Hospital, 3 of which had a family history. Analysis of T(1)WI images enabled us to describe muscle fatty infiltration and STIR images to describe muscle edema. Each muscle was scored according to its fatty degeneration (fat replacement score range from 0-4). Results: The 5 patients were all asymmetrically involved. At the thigh level, the hamstrings were more affected than anterior muscles in 4 patients, and anterior muscles were more affected than hamstrings in only 1 patient. The most affected thigh muscles were usually the adductor magnus, semimembranosus, semitendinosus, femoral biceps long head and vastus medialis muscles (average fat replacement score of each muscle was more than 3). The calves were less affected than thighs.The average fat replacement score of the calf muscles was 1.0 for soleus, 0.9 for medial gastrocnemius, 0.8 for tibialis anterior, and 0.4 for lateral gastrocnemius. There was no fatty infiltration in peroneus and tibialis posterior. 4 out of 5 patients had edema in the lower limb muscles. Conclusion: Asymmetric involvement is a definitely helpful clue suggesting FSHD, and edema is a common phenomenon. At the thigh level, no unique imaging pattern can be highlighted in all the FSHD patients, overall, the hamstring, adductor magnus and vastus medialis are usually the most severely affected muscles. The calf muscles are less affected than the thigh muscles or spared. Soleus, medial gastrocnemius, and tibialis anterior are preferentially involved at the calf level.

[Survey on a norovirus-borne outbreak caused by Gâ ¡.4 Sydney 2012 variant in a university of Guangzhou, 2017].

Objective: To understand the epidemiological and molecular characteristics of a norovirus- borne outbreak caused by GⅡ.4 Sydney 2012 in a university of Guangzhou to provide evidence for the prevention and control strategy on norovirus-caused epidemics. Methods: A self-designed questionnaire was used to collect clinical information from the patients as well as other data related to the epidemic. Pathogen detections were performed through anal swab specimens from the patients, kitchen workers and samples from the environment. Positive samples were further sequenced for phylogenetic analysis. A case-control study was employed to identify the risk factors related to this outbreak. Results: A total of 226 cases of norovirus-borne infection were identified between September 17 and 21, 2017, including 223 students, with an attack rate of 0.73% (223/30 711), and 3 kitchen workers. Students staying in the A dormitory area had the highest attack rate (1.73%, 164/9 459). No clustering was found in different colleges or classes. Results from the case-control study revealed that people who ate at the canteen in A dormitory area during September 18 to 20 was at risk for the onset of illness (OR=10.75, 95%CI: 5.56-20.79). The highest risk was related to the dinner on September 18. Another significant risk factor (OR=3.65, 95%CI: 1.92-6.94) was close personal contact in the same room of the dorm. The 3 norovirus infected kitchen workers were all from the canteen in A dormitory area where the positive rate of norovirus identified in kitchen workers was 26.67% (12/45). Positive samples were sequenced and sub-typed with results showing that the GⅡ.4 Sydney 2012 variant and the nucleotide sequences of cases and kitchen workers were 100% identical. Conclusions: The outbreak was caused by norovirus GⅡ.4 Sydney 2012 variant at campus. Similar outbreaks had been seen since 2013, with the routes of transmission most likely due to food-borne or personal contact.

[Knowledge, attitude and practice to chronic diseases and associated influencing factors in Uygur population in Kashgar area of Xinjiang Uygur Autonomous Region].

Objective: To investigate the knowledge, attitude and practice (KAP) to chronic diseases and associated influencing factors in Uygur adults in Kashgar of southern Xinjiang, and provide basic information for developing ethnic specific prevention and control strategies for chronic diseases. Methods: With stratified cluster random sampling, investigations, including questionnaire survey, physical examination and laboratory tests were performed among local residents who were aged ≥18 years and selected in Shufu county in southern Xinjiang. KAP scores were calculated and unconditional logistic regression models were used to analyze influencing factors. Results: A total of 4 772 Uygur adults were surveyed. The awareness rate of chronic disease related knowledge ranged from 4.32% to 56.04%, while the awareness rate of preventive measures were from 1.76% to 85.18% and the participation rate of prevention program varied from 4.00% to 97.99%. The average KAP score was 15.90±4.20 and the rate of total KAP was 47.86%. Multi-factor analysis suggested the pass rate of total KAP score increased with educational level. Other factors positively associated with 'KAP score pass rate' were commercial insurance investment, hypertension, family history of common chronic diseases, female and abdominal obesity, while overweight was negatively associated with the KAP score pass rate. Conclusions: The KAP level on chronic diseases was low in Uygur adults in Kashgar. It is necessary to continuously implement ethnic targeted health education and health promotion campaigns, especially in low education level, low income level, overweight and male groups.

Association between C807T(C/T) polymorphism of platelet glycoprotein gene and sensitivity to ischemic stroke: a meta-analysis.

Ischemic stroke can lead to loss of neurologic functions. It occurs due to obstruction in blood supply to the brain. It has been proposed that C807T(C/T) polymorphism within the platelet glycoprotein gene may be associated with density and function of glycoprotein Ia/IIa receptors and contributes to the pathogenesis of thrombotic disease. We assessed the association between C807T(C/T) and risk of ischemic stroke. Databases such as PubMed, Medline, Springer, Elsevier Science Direct, Cochrane Library, Google scholar, Wanfang Data (Chinese), and Chinese National Knowledge Infrastructure (CNKI, Chinese) were used to search for relevant studies. We found 16 eligible studies, which totaled to 4897 (case group 2340; control group 2557) participants. Overall, our results showed significant associations between C807T(C/T) polymorphism and risk of ischemic stroke based on T-allele comparisons (T vs C, pooled OR = 0.78, 95%CI = 0.68-0.90, P < 0.01), TT vs CC comparisons (pooled OR = 0.58, 95%CI = 0.42-0.81, P < 0.01), recessive models (TT vs TC + CC, pooled OR = 0.72, 95%CI = 0.59-0.87, P < 0.01) and dominant models (TT + TC vs CC, pooled OR = 0.70, 95%CI = 0.54-0.92, P < 0.05). There was no association in TC vs CC comparisons (pooled OR = 0.81, 95%CI = 0.63-1.04, P > 0.05). Subgroup analyses stratified according to Hardy-Weinberg equilibrium, sample size, and ethnicity also demonstrated significant associations between the two variables. Therefore, C807T(C/T) polymorphism in the platelet glycoprotein gene may be associated with susceptibility to ischemic stroke, and the T allele at this locus may decrease risk to ischemic stroke.

[NF-κB signaling pathway regulate endplate chondrocytes in rat vitro natural degeneration model].

OBJECTIVE: To explore the relationship between nuclear factor (NF)-κB and vitro nature degeneration model of endplate chondrocyte in rats. METHODS: Rats endplate chondrocytes were isolated and cultured in vitro.Rebulated vitro natural degeneration model and cells were divided into control group (P2 cells group), naturally passaged group (P5 cells group) and NF-κB signaling pathway inhibition group (added Bay11-7082 when the passaged to P5 cells). The changes of cellular morphology were observed by inverted phase contrast microscope, the phenotype of endplate chondrocyte were identified by toluidine blue staining, electromagnetic compatibility (EMC) were observed by alcian blue staining.Type Ⅱ collagen, sry related HMG box (SOX)-9, matrix metalloproteinase(MMP)13 and aggrecan genes were detected by real time-polymerase chain reaction (RT-PCR) to verify the degeneration mode.NF-κB transcriptional activity was assessed by examining cytosolic phosphorylated IκBα and nuclear phosphorylated p65 levels by Western blot. RESULTS: With chondrocytes passing, the cells lost the original morphology gradually.Alcian blue stains observed EMC decreased in naturally passaged group.The leave of Type Ⅱ collagen (P5/P2=0.182, P<0.01), aggrecan (P5/P2=0.287, P<0.01) and SOX-9 (P5/P2=0.488, P<0.01) were significantly reduced, MMP13 (P5/P2=1.324, P<0.05) significantly increased.Western blot analysis showed that in P5 cells nuclear phosphorylation p65 and cytosolic levels of phosphorylated IκBα increased and Bay11-7082 treatment attenuated increase in nuclear phosphorylation p65 and blocked acidinduced increase in cytosolic levels of phosphorylated IκBα.Moreover, the leave of Type Ⅱ collagen (Bay11-7082/P5=4.173, P<0.01), aggrecan (Bay11-7082/P5=2.732, P<0.05) and SOX-9 (Bay11-7082/P5=1.567, P<0.05) significantlyincreased, MMP13 (Bay11-7082/P5=0.611, P<0.05) significantly reduced in treatment group. CONCLUSION: Inhibitor NF-κB signaling pathway plays an important role in the vitro degeneration of endplate cartilage.Reasonable regulation of NF-κB signaling pathway may be a new way to prevent Intervertebral disc degeneration.

[Effect and potential mechanism of ß3-adrenoceptor activation on fibrosis in cardiac fibroblast cell].

OBJECTIVE: To observe the effect of ß3 adrenergic receptor (ß3-AR) on fibrosis in cardiac fibroblasts(CFBs) and explore the related mechanisms. METHODS: Neonatal CFBs were divided into negative control group (N-CFC): CFBs without any intervention; group treated with ß3 adrenergic receptor agonist (AngⅡ-CFC-ß3-AR BRL): CFBs treated with 10(-6) mol/L angiotensin Ⅱ(AngⅡ), 1 hour later treated with 10(-5) mol/L ß3 adrenergic receptor agonist (ß3-AR BRL37344); group treated with ß3 adrenergic receptor antagonist (AngⅡ-CFC-ß3-AR SR): CFBs treated with 10(-6) mol/L AngⅡ, 1 hour later treated with 10(-5) mol/L ß3 adrenergic receptor antagonist (ß3-AR SR59230A); and positive control group (AngⅡ-CFC): CFBs treated with 10(-6) mol/L AngⅡonly. Proliferation of CFBs was detected by the method of WST-1. Protein expression of ß3-AR, transforming growth factor ß1 receptor (TGF-ß1-R), transforming growth factor ß1(TGF-ß1), Smad-2, phospho-Smad-2 (p-Smad-2), collagen-Ⅰ (COL-Ⅰ) and collagen-Ⅲ(COL-Ⅲ) was determined by Western blot assay. RESULTS: (1) The proliferation of CFBs was the highest in AngⅡ-CFC-ß3-AR BRL, followed by AngⅡ-CFC-ß3-AR SR and AngⅡ-CFC group (all P<0.05 vs. N-CFC group). (2) The protein expression level of ß3-AR, TGF-ß1-R, TGF-ß1 and p-Smad-2 was in the same order as proliferation of CFBs. (3) The expression level of COL-Ⅰ and COL-Ⅲ protein was also in the same order as proliferation of CFBs. CONCLUSION: Activation of ß3-AR may promote fibrosis of CFBs through the TGF-ß/Smad signaling pathway and thus aggravate myocardial remodeling.

Relationship between EPHX2 gene polymorphisms and essential hypertension in Uygur, Kazakh, and Han.

We investigated the association between rs751141 polymorphisms in the EPHX2 gene and essential hypertension in Uygur, Kazakh, and Han subjects in Xinjiang, China. A total of 302 essential hypertensive patients in Uygur, 267 in Kazakh, and 368 in Han, as well as 323 normotensive controls in Uygur, 284 in Kazakh, and 348 in Han were enrolled in this study. The TaqMan assay was used to detect the rs751141 G/A gene polymorphism in EPHX2. The rs751141 G/A genotype frequencies for the GA+AA genotypes were 40.2% in essential hypertensive subjects and 52.0% in control subjects in the Han population. The frequencies were significantly different between the 2 Han groups (P < 0.01). The rs751141G/A gene polymorphism showed no significant difference between essential hypertensive patients and normotensive controls in Kazakh and Uygur (all P > 0.05). Essential hypertension in Xinjiang was associated with the rs751141 G/A allele gene polymorphism in EPHX2 in Han subjects but not in Kazakh and Uygur subjects. The rs751141 allele gene polymorphism may be an independent protective factor against essential hypertension in the Han population.

Agriculture facilitated permanent human occupation of the Tibetan Plateau after 3600 B.P.

Our understanding of when and how humans adapted to living on the Tibetan Plateau at altitudes above 2000 to 3000 meters has been constrained by a paucity of archaeological data. Here we report data sets from the northeastern Tibetan Plateau indicating that the first villages were established only by 5200 calendar years before the present (cal yr B.P.). Using these data, we tested the hypothesis that a novel agropastoral economy facilitated year-round living at higher altitudes since 3600 cal yr B.P. This successful subsistence strategy facilitated the adaptation of farmers-herders to the challenges of global temperature decline during the late Holocene.

Clinical epidemiology and molecular profiling of human bocavirus in faecal samples from children with diarrhoea in Guangzhou, China.

To understand the clinical epidemiology and molecular characteristics of human bocavirus (HBoV) infection in children with diarrhoea in Guangzhou, South China, we collected 1128 faecal specimens from children with diarrhoea from July 2010 to December 2012. HBoV and five other major enteric viruses were examined using real-time polymerase chain reaction. Human rotavirus (HRV) was the most prevalent pathogen, detected in 250 (22·2%) cases, followed by enteric adenovirus (EADV) in 76 (6·7%) cases, human astrovirus (HAstV) in 38 (3·4%) cases, HBoV in 17 (1·5%) cases, sapovirus (SaV) in 14 (1·2%) cases, and norovirus (NoV) in 9 (0·8%) cases. Co-infections were identified in 3·7% of the study population and 23·5% of HBoV-positive specimens. Phylogenetic analysis revealed 14 HBoV strains to be clustered into species HBoV1 with only minor variations among them. Overall, the detection of HBoV appears to partially contribute to the overall detection gap for enteric infections, single HBoV infection rarely results in severe clinical outcomes, and HBoV sequencing data appears to support conserved genomes across strains identified in this study.

Meta-analysis: oral or enteral nutritional supplementation in cirrhosis.

BACKGROUND: Malnutrition is a common and clinically significant problem in patients with cirrhosis. The impact of nutritional therapy remains unclear. AIM: To provide an up-to-date systematic review and meta-analysis of RCTs of oral or enteral nutritional supplementation (ONS or ENS) on nutritional and clinical outcomes in adult patients with cirrhosis. METHODS: The primary outcome measure was survival. Included: full-text English language RCTs investigating ONS or ENS vs. a standard nonsupplemented diet in patients with cirrhosis. Excluded: parenteral or branched chain amino acids intervention; treatment duration ≤7 days, exclusive evaluation of posttransplant, postsurgical or quality of life outcomes. RESULTS: Six trials (4 ONS/2 ENS) and 470 patients were included with 71% males and median age 53 years. When all studies were combined, there was no reduction in mortality [Relative risk (RR): 0.75 (0.42, 1.32), P = 0.31]. Subgroup analysis of 3 of the 4 ONS studies did demonstrate a mortality reduction [RR: 0.40 (0.18, 0.90), P = 0.03]. Of the 2 ENS studies, one included the sickest patients in the meta-analysis (82% Child Pugh C) and the other had the shortest mean intervention duration (8.6 days), possibly impacting the potential for benefit. Study quality was suboptimal (median Jadad = 2). CONCLUSIONS: Although there is insufficient evidence to definitively state that oro-enteral nutritional supplementation impacts clinical outcomes, on the basis of this analysis, one can be cautiously optimistic that there is the potential for benefit without an increase in adverse events. Adequately powered, Child Pugh stratified studies of at least 1 month in duration are needed to clarify the impact on relevant clinical outcomes.

Antiemetic effects of combined methylprednisolone and tropisetron in mastectomy.

BACKGROUND: Combined dexamethasone and tropisetron have been reported more effective than a single drug therapy in preventing postoperative nausea and vomiting (PONV). However, the safety use of dexamethasone has been questioned recently because of the risk of secondary adrenal deficiency. Therefore, we hypothesized that combined tropisetron and methylprednisolone, a short-lasting corticoid, might provide effective prophylaxis of PONV with less effect on endogenous cortisol level. METHODS: In this study, 224 women undergoing modified radical mastectomy under general anesthesia were randomly divided into three groups: 1) receiving 10 mg tropisetron alone (T, N.=76); 2) 10 mg tropisetron and 8 mg dexamethasone (TD, N.=73); or 3) 10 mg tropisetron and 40 mg methylprednisolone (TM, N.=75) intravenously. Serum cortisol level, episodes of PONV and the need for rescue antiemetic medication were recorded during first 3 days after surgery. RESULTS: Serum cortisol significantly decreased in group TD (5.42±1.87 µg/dL), compared with group TM (14.38±2.01 µg/dL, P<0.01) and group T (19.52±1.53 µg/dL, P<0.001) in the first day postoperatively. In the first 24 hours, the incidence of vomiting was significantly higher in group T (15.8%), compared with group TD (5.5%, P<0.05) and group TM (5.3%, P<0.05), respectively. The overall request for a rescue antiemetic of group T was significantly higher, compared with group TD and group TM (P<0.05). CONCLUSION: Methylprednisolone-tropisetron combination is more effective than tropisetron alone, and as equally effective as dexamethasone-tropisetron combination for preventing acute PONV in mastectomy.

Odd-even width effect on persistent current in zigzag hexagonal graphene rings.

The electronic structure and thus the persistent current of zigzag hexagonal graphene rings are investigated within the tight-binding formalism. The flux-dependent energy spectrum is grouped into bands with six levels per band due to inter-valley scattering at the corners of the ring. It is found that the degeneracy at the Fermi level is determined by the even or odd quality of the ring width N. The sample ring becomes metallic at odd N but semiconducting at even N, showing up a strange odd-even width effect. In metallic rings, the persistent current within a flux period is linearly changed with magnetic flux varphi, while it is a sinusoidal periodical function of varphi in semiconducting rings. In addition, with increasing N, the persistent current exponentially decreases (increases) at odd (even) N, but finally falls into the consistence with each other at enough large N, showing that the odd-even effect may be experimentally observable only in narrow rings.

Sphingosine kinase 1 participates in insulin signalling and regulates glucose metabolism and homeostasis in KK/Ay diabetic mice.

AIMS/HYPOTHESIS: The aim of this study was to determine the potential role of sphingosine kinase 1 (SPHK1), a key sphingolipid metabolic enzyme, in glucose metabolism and homeostasis. METHODS: SMMC-7721 hepatoma cells and C2C12 myotube cells were used to explore the role of SPHK1 in glucose uptake in vitro. KK/Ay type 2 diabetic mice, which were transfected with adenovirus harbouring the human SPHK1 gene by i.v. injection, were used to investigate the glucose-lowering effects of SPHK1 in vivo. RESULTS: The basal glucose uptake and the insulin-stimulated glucose uptake in both 7721 cells and C2C12 cells were markedly enhanced when SPHK1 was overexpressed by adenovirus-mediated gene transfer, whereas they were substantially reduced when the expression of SPHK1 was inhibited or the activity of SPHK1 was blocked. Insulin could activate SPHK1 of both cell lines in a dose-dependent manner. SPHK1 gene delivery significantly reduced the blood glucose level of KK/Ay diabetic mice, but had no effect on that of normal animals. It also attenuated elevated levels of plasma insulin, NEFA, triacylglycerol, cholesterol and LDL, significantly ameliorated hyperglycaemia-induced injury of liver, heart and kidney, and enhanced phosphorylation of insulin-signalling kinases such as Akt and glycogen synthase kinase 3beta in livers of the diabetic animals. CONCLUSIONS/INTERPRETATION: SPHK1 is involved in insulin signalling and plays an important role in the regulation of glucose and fat metabolism; adenovirus-mediated SPHK1 gene transfer might provide a novel strategy in the treatment of type 2 diabetes mellitus.

Determination of dextromethorphan and its metabolite dextrorphan in human urine by capillary gas chromatography without derivatization.

A sensitive, simple and accurate method was developed for determination of dextromethorphan (DM) and dextrorphan (DT) in human urine by capillary gas chromatography without derivatization. After an oral dose of 30 mg DM, urine samples were collected and extracted, then analyzed on 0.22 mmx17 m HP-1 capillary column. DM and its metabolite DT were analyzed simultaneously with good separation. Docosane was used as the internal standard (I.S.). The detector used was flame ionization detector (FID). There was a linear relationship between peak area ratios of analytes to I.S. and concentration of analytes over the concentration range 0.37-7.38 micromol/l for DM and 0.39-77.8 micromol/l for DT. The recovery was 88.1 approximately 103.9% for DM and 86.7 approximately 96.8% for DT. The within-day and between-day coefficients of variation were less than 7.4 and 7.3% (RSD) for the assay of DM and DT in urine, respectively. The limits of detection (LOD) were 0.30 micromol/l for DM and 0.16 micromol/l for DT. The limits of quantitation (LOQ) were 0.37 micromol/l (RSD<6%) for DM and 0.39 micromol/l (RSD<7%) for DT. The method has been applied to determine the oxidative phenotypes of cytochrome P450 2D6 (CYP2D6) in a Chinese population with metabolic ratio of DM in human urine.