[Research progress of sarcopenic obesity and chronic liver disease].

Sarcopenia has attracted increasing attention with the study of nutrition in patients with liver disease. Sarcopenia is an independent risk factor for a poor prognosis of liver disease and is becoming increasingly common in patients with liver disease. Studies have shown that patients with liver disease and sarcopenic obesity have a worse prognosis than patients with liver disease and simple sarcopenia or obesity. In clinical practice, it is easy to recognize patients with malnutrition and decreased muscle mass, but we often ignore those patients with normal body weight or even obesity who will likewise experience muscle mass loss. Simply relying on the monitoring of body mass and body mass index to assess the nutritional and muscle status of patients with liver disease is not accurate. At present, our understanding of the relationship between chronic liver disease and sarcopenic obesity is still poorly understood. In this paper, the research progress on chronic liver disease, sarcopenia, and sarcopenic obesity in recent years is reviewed so as to provide a theoretical basis for improving the clinical prognosis of patients with liver disease.

[Clinical and pathological features of Dubin-Johnson syndrome].

Objective: To explore the clinical and pathological features of Dubin-Johnson syndrome. Methods: The clinical and pathological characteristics of 18 cases of Dubin-Johnson syndrome diagnosed in the Department of Pathology of the Third Affiliated Hospital of Sun Yat-sen University from 2008 to 2018 were analyzed. Related literature was reviewed. Results: There were 15 male and three female patients. The male-to-female ratio was 5∶1. The age of the patients ranged from 17 to 73 years (median 24 years). Common clinical manifestations were jaundice, anorexia, and abnormal liver function tests. The pathological feature was the deposition of dark brown particles in the hepatocytes, especially those around the central veins. Conclusions: Dubin-Johnson syndrome mainly occurs in young people. The characteristic pathological changes are the deposition of dark brown particles in the hepatocytes around the central veins of the liver. The diagnosis of Dubin-Johnson syndrome mainly relies on clinical manifestations, laboratory examinations, histopathological examinations and genetic testing. The understanding of Dubin-Johnson syndrome can help reduce the rates of missed diagnosis and misdiagnosis of the disease.

Development, validity and reproducibility of a whole grain food frequency questionnaire in Malaysian children.

BACKGROUND: To date, there is no validated whole grain assessment tool for children in any Southeast Asian countries. Hence, there is a need for a valid tool to assess whole grain intake among Malaysian children. This study aimed to develop, validate and test the reproducibility of a food frequency questionnaire (FFQ) in estimating whole grain intake among Malaysian children. METHODS: A total of 392 children participated in the FFQ development and 112 children aged 9-12 years participated in the validation phase; with a subsample of 50 children participating in the reproducibility phase. Three-day diet record (3DR) as the reference method in validation phase. Spearman correlations, mean difference, Bland-Altman plot and cross-classification analyses were used to assess validity. The reproducibility was tested through a repeat administration of the FFQ, with 1 month time interval. Reproducibility analyses involved intra-class correlation coefficient (ICC), Cronbach's alpha and cross-classification analyses. RESULTS: The FFQ consisted of 156 whole grain food items from six food groups. Mean intake of whole grain in FFQ1 and 3DR were correlated well (r = 0.732), demonstrated good acceptance of the FFQ. Bland Altman plots showed relatively good agreement for both the dietary methods. Cross-classification of whole grain intake between the two methods showed that < 9.9% of children were grossly misclassified. Outcomes from ICC (0.989) and Cronbach's alpha (0.995) demonstrated excellent reliability. All the children were classified in the same or adjacent quartile of whole grain intake. CONCLUSIONS: Overall, the findings support the validity of the developed FFQ to appropriately estimate the whole grain intake in Malaysian children. This validated FFQ will be a valuable tool for future studies, to analyses the impact of whole grain consumption with disease relationship among Malaysian schoolchildren.

Long-range interactions of the ground state muonium with atoms.

The scaling relations for the dispersion coefficients of long-range interactions between the Mu(1s)-Mu(1s, 2s, or 2p) systems and the H(1s)-H(1s, 2s, or 2p) systems are obtained using analytical properties of hydrogenic wavefunctions, which allows us to obtain the dispersion coefficients for Mu(1s)-Mu(1s, 2s, or 2p) systems from the corresponding H(1s)-H(1s, 2s, or 2p) systems. Additionally, the dispersion coefficients of long-range interactions of Mu(1s) with the ground-state H, noble gas atoms He, Ne, Ar, Kr, and Xe, alkali-metal atoms Li, Na, K, and Rb, alkaline-earth atoms Be, Mg, Ca, and Sr, and Cu, Ag, F, and Cl atoms are calculated.

Overexpression of EPS8L3 promotes cell proliferation by inhibiting the transactivity of FOXO1 in HCC.

The homology of epidermal growth factor receptor pathway substrate 8 (EPS8), EPS8L3, is elevated significantly in hepatocellular carcinoma (HCC) tissues and cell lines compared with the normal liver tissues and cell lines. The MTT and colony formation assays demonstrated that overexpressing EPS8L3 enhances, while silencing reduces the proliferation of HCC cells. Further experiments illustrated that overexpressing EPS8L3 promotes the expression of p-AKT, Cyclin D1, but inhibits the transcriptional activity of FOXO1. Besides, colony formation assay demonstrated that AKT inhibitor suppresses the effect of EPS8L3 on proliferation in EPS8L3-overexpressing cells, whereas AKT restores the proliferation of EPS8L3-silenced cells, suggesting that EPS8L3 might promote proliferation by hyperactivating the AKT signaling pathway and subsequently inhibiting the FOXO1 transcriptional activity. Our results provide new view between EPS8L3 and progression of human HCC, suggesting that EPS8L3 may be a novel therapeutic target for HCC.

[The efficacy of external physical vibration lithecbole in the assistant treatment of the upper urinary tract residual stones: a meta-analysis].

Objective: To determine the clinical effect of Friend-Ⅰ External Physical Vibration Lithecbole (EPVL) by Meta-analysis. Methods: Pubmed, Embase, Medline, Cochrane Library, Chinese National Knowledge Infrastructure were searched for clinical trials comparing EPVL with the conventional treatment. The quality of included studies was assessed and Meta-analysis was conducted by Review Manager 5.3 software. Results: Five randomized or Quasi-randomized controlled trials met the inclusion criteria. The first day stone expulsion rate of EPVL group was superior to the control group (OR=4.95, 95% CI: 3.35-7.32, P<0.000 01). Both one-week (OR=3.13, 95% CI: 1.95-5.04, P<0.000 01) and two-week stone free rate (OR=4.50, 95% CI: 2.02-10.00, P=0.000 2) were statistically higher in the EPVL group than that in the control group. No severe adverse event occurred during the follow-up. Conclusions: Our study suggested that EPVL could be the effective treatment for upper urinary tract residual stone. However, more high quality randomized controlled trials are needed to better affirm this.

Joint effects between urinary selenium and polymorphisms in methylation related genes on breast cancer risk.

The aim of this study was to explore the associations of urinary selenium and polymorphisms in methylation related genes with breast cancer risk and the interactions on the risk. The present study involved in 240 female patients with incident breast cancer and 246 age-matched controls in two affiliated hospitals of Sun Yat-sen University in Guangzhou, China, from October 2009 to July 2010. DNMT1 rs2228611, MTHFR rs1801133, and MTR rs1805087 were genotyped using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Urinary concentration of selenium was measured by inductively coupled plasma mass spectrometry. Women with urinary selenium in the second tertile had a significant reduced breast cancer risk compared to those with urinary selenium in the lowest tertile [OR (95%CI): 0.50 (0.30, 0.81)]. DNMT1 rs2228611, MTHFR rs1801133, and MTR rs1805087 were not associated with breast cancer risk. Women with the third tertile of urinary selenium had a significant reduced breast cancer risk compared to those with the lowest tertile among women only with CC genotype [OR (95%CI): 0.55 (0.30, 1.00)] but not CT/TT genotypes [OR (95%CI): 1.58 (0.73, 3.42)] of MTHFR rs1801133 (P for interaction=0.044). Our results suggested that selenium was associated with a decreased risk of breast cancer and this beneficial effect was limited to women with CC genotype of MTHFR rs1801133.

Towards a clinical consensus on the management of pregnancy and birth after laparoscopic and open myomectomy: A survey of obstetricians and gynaecologists.

OBJECTIVES: The primary aim was to assess if a clinical consensus regarding the management of pregnancy post myomectomy existed amongst consultant obstetricians and gynaecologists. Secondary objectives were to evaluate factors which influence the clinician's decision making in this group of women. STUDY DESIGN: Electronic survey sent to all consultants working in the North Central and East London deanery, Kent Surrey and Sussex deanery and Imperial NHS Trust to assess opinions on mode of birth post myomectomy, intervals advised to pregnancy post myomectomy, factors influencing the management of delivery in the scarred uterus post myomectomy, opinions on induction of labour and questions relating to operative notes. RESULTS: 209 consultant responses received between 07/03/2022-07/05/2022 (44% response rate); 77% (161/209) practicing obstetricians and gynaecologists, 10% (21/109) pure gynaecologists and 13% (27/209) pure obstetricians. The majority would support a vaginal birth after open myomectomy (75%) and laparoscopic myomectomy (79%). No consensus was found as to the optimal time interval between myomectomy and pregnancy. Higher frequency of performing myomectomy and a greater level of experience were significantly associated with a shorter interval to pregnancy advised. The most important operative factors influencing decision to support trial of labour post myomectomy were breach of uterine cavity; location of fibroids removed and number of incisions on the uterus. 77% believe women should be given a choice regarding mode of delivery post myomectomy in a similar way to previous LSCS. 82.8% would support enrolment of patients into a prospective trial to investigate delivery post myomectomy. CONCLUSIONS: We present a comprehensive survey of clinician opinions on pregnancy post myomectomy demonstrating that the majority of consultant obstetricians and gynaecologists sampled would support vaginal birth post myomectomy; counselling patients in a similar way to VBAC; a standardised myomectomy operation note and enrolment of patients in a future prospective trial. Wide variation in opinion regarding interval to pregnancy post myomectomy has been highlighted. We believe this information will facilitate counselling discussions and empower women with subsequent pregnancies after myomectomy to make an informed decision on mode of birth post myomectomy.

Molecular studies of the congenital malformation induced by Largehead Atractylodes Rhizome, the most commonly used Chinese medicine for threatened miscarriage.

Largehead Atractylodes Rhizome (LAR) is the most commonly used Chinese herbal medicine for threatened miscarriage. Potential reproductive toxicity of LAR was identified in early pregnancy in animals. Skeletal anomalies including loss of ulna and distal digits, shortening of humerus and radius were observed in higher clinical dose groups. Here, we aimed to study the molecular mechanism of the congenital malformation induced by LAR. In vitro whole mouse embryo culture was used to confirm the embryotoxicity effects of LAR on developing limb buds during early organogenesis. A pregnant mouse model was employed to study the developmental gene expression by quantitative PCR and whole hybridization and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling staining, in the forelimbs and hindlimbs during development in vivo. Severe growth retardation, multiple embryonic malformations and delayed limb bud development were observed. Limb-specific Tbx gene expressions in both developing forelimbs and hindlimbs were significantly decreased. Increased developmental apoptosis in apical ectodermal ridge and mesenchymal mesoderm of the developing limb buds was identified. Overexpressions of Tbx2 and Tbx3 in embryos in vitro rescued LAR-induced abnormal limb development and reduced apoptosis in the developing forelimb buds. In conclusion, LAR affects limb development by suppressing the expression of limb developmental genes and disturbing programmed cell death during limb formation in mice.

Effect of CYP3A4*1G on the fentanyl consumption for intravenous patient-controlled analgesia after total abdominal hysterectomy in Chinese Han population.

WHAT IS KNOWN AND OBJECTIVE: Clinical investigations into postoperative intravenous patient-controlled analgesia (PCA) have indicated interindividual differences in fentanyl consumption. Cytochrome P450 3A4 (CYP3A4) is the main metabolism enzyme of fentanyl, and single nucleotide polymorphisms within the CYP3A4 gene may contribute to the variability of fentanyl analgesic efficacy. The aim of this study was to investigate whether the most common genetic variation in Chinese, CYP3A4*1G, has an impact on the fentanyl consumption for intravenous PCA in Chinese Han women undergone abdominal total hysterectomy. METHODS: A total of 79 female patients (American Society of Anesthesiologist physical status I or II) scheduled to undergo elective abdominal total hysterectomy were enrolled. All patients received combined spinal-epidural anaesthesia with bupivacaine. Intravenous fentanyl PCA was provided postoperatively for satisfactory analgesia. The doses of fentanyl consumption were recorded 2, 4, 24 and 48 h after the initiation of PCA postoperatively. Pain at rest and adverse effects were measured with rating scales. CYP3A4*1G was screened by means of direct sequencing and further confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS AND DISCUSSION: Forty-six patients were GG homozygotes, 27 patients were GA heterozygotes, and six patients were AA homozygotes, respectively. The distribution of the CYP3A4*1G allele was consistent with Hardy-Weinberg equilibrium (P>0·05). At 2 and 4 h, the doses of fentanyl required for patients with GA/AA genotypes were 80·0 (45·0, 112·5) µg and 120·0 (80, 173·8)µg, respectively, and significantly lower than those for GG homozygotes [91·3 (80·0, 125·0) µg and 169·0 (112·5, 226·3) µg, respectively, P<0·05]. There was trend of decreasing fentanyl consumption at 24 and 48h in patients with GA/AA genotypes, relative to GG homozygotes, but the difference was not statistical significant (P>0·05). WHAT IS NEW AND CONCLUSIONS: CYP3A4*1G has an impact on the analgesic effect of fentanyl in Chinese Han subjects. Further validation of our results in a well-powered study would be helpful.

Potential reproductive toxicity of Largehead Atractylodes Rhizome, the most commonly used Chinese medicine for threatened miscarriage.

BACKGROUND: Largehead Atractylodes Rhizome (LAR) is the most commonly used Chinese medicine to prevent early pregnancy loss due to threatened miscarriage. However, its safety profile during pregnancy is still not available. Here we aimed to identify the potential adverse effects of LAR on embryo-fetal development as well as prenatal and post-natal growth. METHODS: Pregnant mice, rats and rabbits were orally administered with LAR extracts in various doses (from 1×, 2×, 3× and up to 6× clinical doses) at different gestational periods (implantation, gastrulation, organogenesis, maturation and whole gestation). Maternal effects on weight loss, implantation failure and fetal resorption and perinatal effects on developmental delay, growth restriction and congenital malformations were studied. RESULTS: In mice, with early LAR exposure, a significant decrease in fetal growth parameters and a significant increase in post-implantation loss were identified. With late LAR exposure, significant increases in gestational duration as well as prenatal and post-natal mortality were found. At high clinical doses, congenital skeletal malformations were recorded. In rabbits, fetal resorption, hydrops fetalis and short ear anomaly were observed. No significant adverse effects were found in rats. CONCLUSIONS: Potential reproductive toxicity of LAR in pregnant animals was identified within the clinical dose. Caution should be taken in clinical applications of LAR during pregnancy.

Laparoscopic management of a full-thickness uterine niche with subsequent pregnancy outcome.

BACKGROUND: Uterine niche is the consequence of impaired healing of the myometrium following a lower segment transverse caesarean section (CS). Although there is conflicting evidence on the management of these cases, laparoscopic repair is a commonly used surgical treatment modality. OBJECTIVES: To demonstrate the management and laparoscopic repair of the niche with subsequent pregnancy outcome. MATERIALS AND METHODS: We report a case of a 33-year-old patient who had a significant haematoma in the niche. The haematoma resolved after conservative management however, she remained symptomatic. Therefore, she had a laparoscopic repair. The narrated surgical video article demonstrates the dissection of the uterovesical fold overlying the niche, followed by the excision of the scar tissue and its repair with laparoscopic suturing. Ultrasound and magnetic resonance imaging images of the uterus demonstrating the haematoma at the caesarean section site, the niche after resolution of the haematoma and post-repair imaging are also provided. MAIN OUTCOME MEASURES: Repair of the niche, symptomatic relief of abnormal uterine bleeding, spontaneous conception and live birth. Ultrasonographic images also demonstrate uterine wall continuity post laparoscopic repair. RESULTS: The patient recovered uneventfully. Full-thickness of myometrium was demonstrated with post-operative imaging and confirmed at the subsequent caesarean section. Gynaecological symptoms resolved following the repair. The patient conceived spontaneously after surgery and delivered at term by caesarean section without any complications. CONCLUSION: Laparoscopic management of the niche should be considered where there is a complete myometrial defect or significant thinning of the myometrium, especially in symptomatic women who desire future pregnancy.

Incidence of right-sided colorectal cancer after breast cancer: a population-based study.

OBJECTIVES: Estrogen levels, which are involved in the development of breast cancer, may also be responsible for a higher incidence of right-sided colorectal neoplasia in women. Our objective was to determine the incidence of right-sided colorectal cancer (CRC) after the diagnosis of breast cancer. METHODS: All cases of breast cancers diagnosed between 1956 and 2006 were identified from the Manitoba Cancer Registry (MCR) and followed up until the diagnosis of any invasive cancer, death, migration out of the province, or 31 December 2006. Standardized incidence ratios (SIRs) for all CRC and right-sided CRC (cecum, ascending colon, and hepatic flexure) were calculated to compare the observed CRC incidence with that expected in the general population. Stratified analysis was performed to determine the risk at different follow-up time intervals, age at breast cancer diagnosis, and for tamoxifen use. RESULTS: There were 23,377 cases of breast cancer diagnosed between 1956 and 2006 with a total follow-up of 221,364 patient-years. The SIR for all CRC was 0.96 (95% confidence interval (CI) 0.87-1.06) and for right-sided CRC it was 1.02 (95% CI 0.87-1.20). The SIRs remained close to unity at different time intervals, for different age groups, and in analysis restricted to more recent years (1985-2006). Tamoxifen use did not alter the risk of all CRC (SIR 1.22; 95% CI 0.92-1.62) or right-sided CRC (SIR 0.90; 95% CI 0.48-1.54). CONCLUSIONS: There is no increase in the overall risk for CRC or for right-sided CRC after the diagnosis of breast cancer. CRC screening strategy for breast cancer survivors should be similar to that for the general population.

[Epidemiological characteristics of HIV infected pregnant women and exposed infants in Guangdong province, 2014-2017].

Objective: To analyze the epidemiological characteristics of HIV-infected pregnant women and exposed infant in Guangdong province and identify the factors associated with infant HIV infection through mother-to-child transmission. Methods: National Information System for Prevention of mother-to-child HIV Transmission and Early Infant Diagnosis Information Management Platform were used to collect the individual information about HIV-infected pregnant women and exposed infants who were delivered in Guangdong from January 1, 2014 to December 31 in 2017. The differences in pregnant women's demographic data, history of pregnancy and childbirth, the utilization of mother-to-child transmission prevention services and early infant diagnosis between the infected HIV exposed infants and uninfected HIV exposed infants were compared, and univariate and multivariate logistic regression analyses were conducted to identify the factors associated with mother-to-child HIV transmission. Results: Among 349 HIV infected pregnant women, the proportions of the pregnant women whose HIV infection status were confirmed before pregnancy, during pregnancy and at or after childbirth were 30.4% (106/349), 49.6% (173/349) and 20.0% (70/349) respectively. The proportions of those with sexual partners whose HIV infection status were unknown and those receiving no antiviral treatment were 39.5% (138/349) and 13.2% (46/349) respectively. Among the HIV exposed infants, the mother-to-child transmission rate was 4.2%(15/353), the HIV exposed infants had the first or second early diagnosis tests within 44 (P(25)-P(75): 42-50) days and 96 (P(25)-P(75): 92-106) days after birth, respectively. Univariate logistic regression analysis indicated that the risk for mother-to-child HIV transmission increased in those whose HIV infection status were confirmed at or after childbirth compared with before pregnancy (OR=5.72, 95%CI: 1.52-21.61) and in the group that antiviral treatment was given to either mothers or infants compared with the group that antiviral treatment was given to both mothers and infants (OR=33.56, 95%CI: 9.04-124.55), while there was lower mother-to-child HIV transmission risk in artificial feeding group compared with breast feeding group (OR=0.07, 95%CI: 0.01-0.76). Conclusion: The risk of mother-to-child HIV transmission in Guangdong can be effectively reduced by the measures of early diagnosis, antiviral treatment and artificial feeding as well as the improvement of mother-to-child transmission prevention service.

FLAIR2 improves LesionTOADS automatic segmentation of multiple sclerosis lesions in non-homogenized, multi-center, 2D clinical magnetic resonance images.

BACKGROUND: Accurate segmentation of MS lesions on MRI is difficult and, if performed manually, time consuming. Automatic segmentations rely strongly on the image contrast and signal-to-noise ratio. Literature examining segmentation tool performances in real-world multi-site data acquisition settings is scarce. OBJECTIVE: FLAIR2, a combination of T2-weighted and fluid attenuated inversion recovery (FLAIR) images, improves tissue contrast while suppressing CSF. We compared the use of FLAIR and FLAIR2 in LesionTOADS, OASIS and the lesion segmentation toolbox (LST) when applied to non-homogenized, multi-center 2D-imaging data. METHODS: Lesions were segmented on 47 MS patient data sets obtained from 34 sites using LesionTOADS, OASIS and LST, and compared to a semi-automatically generated reference. The performance of FLAIR and FLAIR2 was assessed using the relative lesion volume difference (LVD), Dice coefficient (DSC), sensitivity (SEN) and symmetric surface distance (SSD). Performance improvements related to lesion volumes (LVs) were evaluated for all tools. For comparison, LesionTOADS was also used to segment lesions from 3 T single-center MR data of 40 clinically isolated syndrome (CIS) patients. RESULTS: Compared to FLAIR, the use of FLAIR2 in LesionTOADS led to improvements of 31.6% (LVD), 14.0% (DSC), 25.1% (SEN), and 47.0% (SSD) in the multi-center study. DSC and SSD significantly improved for larger LVs, while LVD and SEN were enhanced independent of LV. OASIS showed little difference between FLAIR and FLAIR2, likely due to its inherent use of T2w and FLAIR. LST replicated the benefits of FLAIR2 only in part, indicating that further optimization, particularly at low LVs is needed. In the CIS study, LesionTOADS did not benefit from the use of FLAIR2 as the segmentation performance for both FLAIR and FLAIR2 was heterogeneous. CONCLUSIONS: In this real-world, multi-center experiment, FLAIR2 outperformed FLAIR in its ability to segment MS lesions with LesionTOADS. The computation of FLAIR2 enhanced lesion detection, at minimally increased computational time or cost, even retrospectively. Further work is needed to determine how LesionTOADS and other tools, such as LST, can optimally benefit from the improved FLAIR2 contrast.

Clinical and molecular features of mitochondrial DNA depletion due to mutations in deoxyguanosine kinase.

Published mutations in deoxyguanosine kinase (DGUOK) cause mitochondrial DNA depletion and a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia. In this series, we have identified 15 different mutations in the DGUOK gene from 9 kindreds. Among them, 12 have not previously been reported. Nonsense, splice site, or frame-shift mutations that produce truncated proteins predominate over missense mutations. All patients who harbor null mutations had early onset liver failure and significant neurological disease. These patients have all died before 2-years of age. Conversely, two patients carrying missense mutations had isolated liver disease and are alive in their 4th year of life without liver transplant. Five subjects were detected by newborn screening, with elevated tyrosine or phenylalanine. Consequently, this disease should be considered if elevated tyrosine is identified by newborn screening. Mitochondrial DNA content was below 10% of controls in liver in all but one case and modestly reduced in blood cells. With this paper a total of 39 different mutations in DGUOK have been identified. The most frequent mutation, c.763_c.766dupGATT, occurs in 8 unrelated kindreds. 70% of mutations occur in only one kindred, suggesting full sequencing of this gene is required for diagnosis. The presentation of one case with apparent viral hepatitis, without neurological disease, suggests that this disease should be considered in patients with infantile liver failure regardless of the presence of neurological features or apparent infectious etiology.

Modest Overweight and Healthy Dietary Habits Reduce Risk of Dementia: A Nationwide Survey in Taiwan.

BACKGROUND: Evidence of the associations of dietary habits and body mass index with dementia is inconsistent and limited in East Asian countries. OBJECTIVE: We aim to explore the associations of dietary habits and body mass index with the odds of dementia. DESIGN: Cross-sectional observational study. SETTING: A nationwide, population-based, door-to-door, in-person survey. PARTICIPANTS: Selected by computerized random sampling from all 19 counties in Taiwan. MEASUREMENT: Diagnosis of dementia using the criteria recommended by the National Institute on Aging-Alzheimer's Association. Lifestyle factors, dietary habits and demographic data were compared between normal subjects and participants with dementia. RESULTS: A total of 10432 residents were assessed, among whom 2049 were classified as having a mild cognitive impairment (MCI), 929 were diagnosed with dementia, and 7035 were without dementia or MCI. After adjustment for age, gender, education, body mass index (BMI), dietary habits, habitual exercises and co-morbidities, including hypertension, diabetes and cerebrovascular diseases, we found inverse associations of dementia with the consumption of fish (OR 0.62, 95% CI 0.41-0.94), vegetables (OR 0.35, 95% CI 0.13-0.95), coffee (OR 0.59, 95% CI 0.35-0.97), green tea (OR 0.51, 95% CI 0.34-0.75) and other types of tea (OR 0.41, 95% CI 0.28-0.60). There was no association between dementia and fruit consumption. Compared with people who had a normal BMI (18 < BMI <= 24), older overweight people (24 < BMI <=30) had a reduced risk of dementia with an adjusted OR of 0.77 (95% CI 0.61-0.96). CONCLUSIONS: Our study provides preliminary evidence that suggests that the consumption of fish, vegetables, tea, and coffee has potential benefits against dementia in East Asian population. Being modestly overweight (nadir risk at BMI = 25) in late life was associated with decreased odds of dementia. The benefit of fruits may be offset by their high sugar content.

Ablation of Tacr2 in mice leads to gastric emptying disturbance.

BACKGROUND: Tacr2 is one of the G protein-coupled receptors(GPCRs) that mediate the biological actions of tachykinins. It is abundantly expressed in the gastrointestinal (GI) system and is thought to play an important role in GI motility, secretion, and visceral sensitivity. Previously, the physiological and pathophysiological functions of Tacr2 were mainly studied using Tacr2 selective agonists or antagonists. Here, we seek to investigate the effect of Tacr2 disruption in mice to provide further insights. METHODS: The Tacr2 knockout mice were generated by homologous recombination and the phenotypic changes of the Tacr2-null mice were analyzed and compared with their wild type (wt) littermates. KEY RESULTS: Increased food retention was detected in Tacr2-/- mice. The stomach of Tacr2-/- mice had thinner muscularis externa and less neurons in the myenteric plexus. The stomach and small intestine exhibited longer duration of electrical field stimulation (EFS)-induced inhibition in the gastric fundus and decreased frequency of migrating motor complex (MMC), respectively. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were significantly up-regulated due to Tarc2 deficiency, contributing to enhanced nitric oxide (NO) signaling in the stomach of Tacr2-/- mice. Intraperitoneal application of 7-nitroindazole (7-NI) to Tacr2-/- mice effectively relieved the gastric emptying disturbance. Moreover, Creb and NF-κB signalings were involved in the regulation of these physiological changes initiated by Tacr2 deficiency. CONCLUSIONS & INFERENCES: Tacr2 negatively regulated the expression of nNOS and VIP both in vivo and in vitro. Its ablation in mice elevated the expression of nNOS and VIP, enhanced NO signaling and changed the Creb and NF-κB signalings, finally leading to the gastric emptying disturbance of Tacr2-/- mice.