Search

Study design:Case control.Objective:To clarify the predictors of low blood pressure (BP) and hyponatremia after spinal cord injury (SCI) and to discuss their pathophysiology.Setting:A SCI center in Japan.Methods:Age, gender, initial ASIA impairment scale (AIS) score, BP, blood electrolytes (sodium, K and Cl) and biochemical markers were evaluated at 1 month after injury. Risk factors of low BP and hyponatremia were analyzed using uni- and multivariate logistic regression models.Results:This study comprised of 172 SCI patients. Initial AIS score (Odds ratio (OR): 1.24, 95% confidence intervals (CI) 1.13-1.49, P-value <0.01) and hyponatremia (OR: 3.71, 95%CI 1.27-6.96, P<0.01) were the most important risk factors of low BP. As a second step, risk factors of hyponatremia were initial AIS score (OR: 1.36, 95%CI 1.08-2.78, P<0.01) and age (OR: 1.55, 95%CI 1.17-2.93, P<0.01).Conclusions:In acute and subacute period, the more severe SCI and lower AIS score patients have the more frequently low BP and/or hyponatremia do appear. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) poses a global health threat, with the oral microbiome increasingly implicated in its pathogenesis. This study leverages Mendelian Randomization (MR) to explore causal links between oral microbiota and CRC using data from the China National GeneBank and Biobank Japan. By integrating multi-omics approaches, we aim to uncover mechanisms by which the microbiome influences cellular metabolism and cancer development., Methods: We analyzed microbiome profiles from 2017 tongue and 1915 saliva samples, and GWAS data for 6692 CRC cases and 27178 controls. Significant bacterial taxa were identified via MR analysis. Single-cell RNA sequencing and enrichment analyses elucidated underlying pathways, and drug predictions identified potential therapeutics., Results: MR identified 19 bacterial taxa significantly associated with CRC. Protective effects were observed in taxa like RUG343 and Streptococcus&#95;umgs&#95;2425, while HOT-345&#95;umgs&#95;976 and W5053&#95;sp000467935&#95;mgs&#95;712 increased CRC risk. Single-cell RNA sequencing revealed key pathways, including JAK-STAT signaling and tyrosine metabolism. Drug prediction highlighted potential therapeutics like Menadione Sodium Bisulfite and Raloxifene., Conclusion: This study establishes the critical role of the oral microbiome in colorectal cancer development, identifying specific microbial taxa linked to CRC risk. Single-cell RNA sequencing and drug prediction analyses further elucidate key pathways and potential therapeutics, providing novel insights and personalized treatment strategies for CRC., Competing Interests: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gu, Jiang, Shui, Luo, Zhou, Zhang, Jiang, Huang, Chen, Tang, Fu, Luo, Yang, Xu, Chi, Liu and Huang.)

Objectives: To evaluate and compare the burden of gastric cancer in adolescents and young adults (GCAYA) among China, South Korea, Japan and the USA, four countries with similar or different rates of gastric cancer (GC) incidence, development levels and cancer control strategies., Design: This population-based observational study collected the epidemiological data of GCAYA from the Global Burden of Diseases Study 2019. The trend magnitude and directions over time for incidence and mortality of GCAYA were analysed and compared among four countries., Main Outcomes and Measures: Outcomes included new cases, deaths, mortality-to-incidence ratios (MIRs), disability-adjusted life years, and their age-standardised rates and estimated annual percentage changes (AAPCs)., Results: There were 49 008 new cases and 27 895 deaths from GCAYA in 2019, nearly half of which occurred in China. The AAPCs for the age-standardised incidence and mortality rate were 0.3 (-0.1 to 0.7), -3.6 (-3.7 to -3.4), -3.2 (-3.8 to -2.6), -0.1 (-0.6 to 0.5) and -2.0 (-2.3 to -1.6), -5.6 (-6.2 to -5.0), -4.4 (-4.7 to -4.1), -0.7 (-1.0 to -0.3) in China, South Korea, Japan and the USA, respectively. The incidence rate for females in the USA rose by 0.4% annually. GC ranks fifth, first, fourth and ninth in China, South Korea, Japan and the USA regarding burdens caused by cancer in adolescents and young adults. The MIRs declined constantly in South Korea and China, and the MIR in the USA became the highest in 2019., Conclusions: Although not covered by prevention and screening programmes, variations in disease burden and time trends may reflect variations in risk factors, cancer control strategies and treatment accessibility of GC among the four countries. Investigating the reasons behind the varying disease burden and changing trends of GCAYA across countries will inform recommendations for prevention measures and timely diagnosis specific to this underserved population to further decrease the GC burden., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Purpose: The institutional database of the Thyroid Surgery Division in China-Japan Union Hospital of Jilin University was queried to audit time trend patterns in thyroid cancer (TC) management between 2008 and 2017., Methods: Retrospective longitudinal analysis. Clinicopathological features and treatment strategies were analyzed. Frequencies and multivariate tests were used to detect correlations., Results: Clinical data were obtained from 15,000 TC patients (i.e., 71.3% of 21,044 operations). Papillary was the most common histological subtype (n = 14,916, 99%), and 76% were microcarcinomas. Stage I (95%) and low-risk patients (58%) were prevalent throughout the 10-year period. The trend for total thyroidectomy increased from 29.1% (2008-2012) to 67.9% (2013-2015), and then dropped to 48.6% (2016-2017). A total of 8827 (52%) patients received central lymph node dissection (CLND). The tendency for CLND increased from 15.7 to 86.4% during the 10-year period. While the trend of lateral lymph node dissection decreased from 71.3 to 13.3%. Radioactive iodine therapy was offered to 10% of patients (2008-2012), except for a low value (5.4%) in 2009, and then increased from 12.3% (2012) to 41.3% (2015), while decreased to 32.4% (2017)., Conclusion: The surgical management of TC patients has undergone continuous changes over the past 10 years. The evolution from aggressive treatment to a more conservative approach has been constant. Our results suggest that the current surgical management approach for TC is adequate and in support of the published guidelines. Our findings warrant further investigation to determine the clinical implications of decision making for TC.

This study aimed to determine the plasma and tissue residue depletion kinetics of doxycycline (DC) in grass carp (Ctenopharyngodon idella) after daily oral administrations at 20 mg/kg for 3 days, and to calculate the corresponding withdrawal times. Following drug administrations, samples of plasma, liver, kidney, gill and muscle + skin were collected at predetermined time points (0.25, 0.5, 1, 3, 5, 7, 14, 21, 28, 35, 42, 49 and 56 days) and analyzed for concentrations of DC using a LC-MS/MS method. The results showed that liver had the highest concentrations and the slowest depletion compared to other tissues, with detectable DC up to 49 days (58.9 ± 12.8 μg/kg). The WT 1.4 software and "reschem" package were used to calculate withdrawal times, and the results were similar. The results suggest a withdrawal time of 41 days for Europe and China and 50 days for Japan is needed for DC in grass carp after 3 daily oral administrations at 20 mg/kg. Overall, this study improves our understanding of the tissue residue depletion kinetics of DC in fish, and the results may help regulatory agencies to determine proper withdrawal periods based on different regulatory standards in different countries to ensure safety of aquatic food products., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The let-7 microRNAs (miRNAs), a class of small noncoding RNAs, are phylogenetically conserved and temporally expressed and control the proper timing of events during development as heterochronic genes in many animals. Japanese flounder (Paralichthys olivaceus) undergoes a metamorphosis from the larval to juvenile form. Here, we identified 21 let-7 miRNA precursors from different genome loci in Japanese flounder. P. olivaceus let-7 miRNAs are widely expressed in adult tissues, highly expressed during metamorphosis, but weakly during embryonic development. Exogenous thyroid hormone (0.1 mg/L), which induces premature metamorphosis, significantly promotes the expression of let-7 miRNAs, while thiourea (30 mg/L), which affects metamorphic arrest, inhibits the expression of let-7 miRNAs in metamorphosis in P. olivaceus. These results show that let-7 miRNAs widely participate in tissue development and metabolism during development and are also involved in regulation of temporal transitions associated with cell proliferation and differentiation during metamorphosis, in P. olivaceus., (Published by Elsevier Inc.)

Background: MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs of 20-25 nucleotides that play a key role in diverse biological processes. Japanese flounder undergo dramatic metamorphosis in their early development. The metamorphosis is characterized by morphological transformation from a bilaterally symmetrical to an asymmetrical body shape concomitant with extensive morphological and physiological remodeling of organs. So far, only a few miRNAs have been identified in fish and there are very few reports about the Japanese flounder miRNA., Methodology/principal Findings: Solexa sequencing technology was used to perform high throughput sequencing of the small RNA library from the metamorphic period of Japanese flounder. Subsequently, aligning these sequencing data with metazoan known miRNAs, we characterized 140 conserved miRNAs and 57 miRNA: miRNA* pairs from the small RNA library. Among these 57 miRNA: miRNA* pairs, twenty flounder miRNA precursors were amplified from genomic DNA. We also demonstrated evolutionary conservation of Japanese flounder miRNAs and miRNA* in the animal evolution process. Using miRNA microarrays, we identified 66 differentially expressed miRNAs at two metamorphic stages (17 and 29 days post hatching) of Japanese flounder. The results show that miRNAs might play a key role in regulating gene expression during Japanese flounder metamorphosis., Conclusions/significance: We identified a large number of miRNAs during flounder metamorphosis, some of which are differentially expressed at two different metamorphic stages. The study provides an opportunity for further understanding of miRNA function in the regulation of flounder metamorphosis and gives us clues for further studies of the mechanisms of metamorphosis in Japanese flounder.

Background: The genes responsible for insulin resistance are also candidate genes for insulin resistance-related diseases, such as obesity and hypertension. Functional polymorphisms in the beta2- and beta3-adrenergic receptors have been reported to be associated with diabetes, hypertension, and obesity. To clarify the relevance of the beta-adrenergic receptor polymorphisms to insulin resistance, we studied their association with polymorphisms of beta2 (Arg16Gly, Gln27Glu) and beta3 (Trp64Arg) adrenoceptor genes., Methods: We studied 155 young, nonobese Japanese men using the homeostasis model assessment of insulin resistance (HOMA-IR) to divide individuals into insulin-sensitive and insulin-resistant groups. Insulin resistance in the participants was defined as HOMA-IR equal to or greater than the average plus 1 SD of 3.1. There were 69 men who were insulin resistant and 86 men who were insulin sensitive. Body mass index (BMI), blood pressure (BP), plasma glucose, insulin, leptin, norepinephrine (NE) levels, and the polymorphisms of Arg16Gly and Gln27Glu of the beta2- and Trp64Arg of the beta3-adrenoceptor polymorphisms were measured in all participants., Results: The insulin-resistant group had higher frequency of the Gly16 allele of Arg16Gly compared with the insulin-sensitive group, whereas the frequencies of genotypes or alleles of Gln27Glu and Trp64Arg were similar. The insulin-resistant group had a higher mean HOMA-IR, fasting insulin, NE, and total fat mass compared with levels in the insulin-sensitive group, but the BMI and leptin levels were similar. The subjects carrying the Gly16 allele of the beta2-adrenoceptor gene had a higher mean HOMA-IR, fasting insulin, NE, body fat mass, and BP than those without the Gly16 allele., Conclusions: The Gly16 mutation of the beta2-adrenoceptor gene is associated with increased insulin resistance, adiposity, and BP accompanied by higher plasma NE levels early in the metabolic disease in developing obesity. These findings show an important role of beta2-adrenoceptor gene polymorphisms in the association of insulin resistance in hypertension and obesity.

Objectives: The apolipoprotein epsilon 4 allele (APOE/epsilon 4) increases plasma cholesterol level and the risk for the late onset type of Alzheimer's disease. However, the correlation between hypertension and APOE/epsilon 4 has not yet been clarified. To examine the APOE/epsilon 4 effect in the general population of Japan, we performed a large genetic epidemiological survey (the Suita Study)., Design and Methods: The Suita Study was a cohort study based on a random sample of 14,200 Japanese residents of Suita city. Subjects who gave informed consent for genetic analysis were recruited in the current study ( = 3997). APOE polymorphism was clearly determined by the TaqMan polymerase chain reaction method., Results: Subjects with APOE/epsilon 4 were significantly ( P < 0.03) more frequent (19.7%) in normotensives than in hypertensives (16.9%), the estimated odds ratio for hypertension (with APOE/epsilon 4 versus without APOE/epsilon 4) being 0.83 [95% confidence interval (CI), 0.70-0.98]. The significance of the association (OR = 0.64; 95% CI, 0.48-0.86) was increased in young subjects ( < or = 60 years old) but disappeared in old subjects. APOE/epsilon 4 also significantly contributed to a 2.9% increase of total cholesterol, 11.8% increase of triglyceride and 3.2% of decrease of high-density lipoprotein-cholesterol., Conclusions: We concluded that APOE/epsilon 4 was associated with an increase of plasma lipid levels and with a decrease of systolic blood pressure. The final conclusion on whether APOE/epsilon 4 contributes to the risk for cardiovascular disease will be clarified by analysis of the cumulative incidence, which will be obtained in the future Suita Study.

A recent report based on the results of 2 epidemiological studies, the Etude Cas-Temoin de l'Infarctus Myocarde (ECTIM) and the Glasgow Heart Scan Study, revealed that a G/T polymorphism with an amino acid substitution (Lys-->Asn) at codon 198 in exon 5 of the endothelin-1 gene (ET-1) is associated with blood pressure in overweight people. They suggested that G/T polymorphism of ET-1 strongly interacted with body mass index (BMI) in the determination of BP levels. To examine interaction among G/T polymorphism of ET-1, BMI, and BP, we performed an association study in a general Japanese population. Subjects (n=1250) were recruited from Ohasama, a cohort in a rural community of northern Japan. DNA was extracted from buffy coat of participants, and G/T polymorphism of ET-1 was determined by the TaqMan probe polymerase chain reaction method, a powerful tool for semiautomatic genotype determination of a large number of samples. Frequency of T (Asn 198) allele in Japanese (27%) was slightly but significantly higher than in whites (24%). Baseline characteristics (age, BMI, systolic and diastolic BP, and antihypertensive treatment) of all subjects were not significantly different according to the genotype of G/T polymorphism. However, in obese subjects (> or =25 kg/m(2)) diastolic BPs were significantly associated with G/T polymorphism of ET-1. After adjustment for confounding factors, significant association remained; for overweight subjects, diastolic BP level in those with T allele (GT + TT) was 1.8 mm Hg (P=0.04) higher than in those with GG genotype. That similar results were obtained from subjects of different races suggests that the Lys198Asn polymorphism of ET-1 is involved in determination of BP levels in obese subjects.

Predisposition to essential hypertension is associated with gene polymorphisms of the renin angiotensin system (RAS). Gene polymorphisms of the angiotensinogen and angiotensin converting enzyme genes are known to be risk factors for hypertension, while few studies concerning the renin gene polymorphism have been published. In the present investigation, we carried out a case control study using a Japanese population to examine the genetic influence of the renin gene on the predisposition to hypertension. Patients (n=235) recruited from outpatients at Osaka University Hospital and diagnosed with essential hypertension or receiving long-term antihypertensive medication participated in the study. Normotensive control subjects (n=510) without a history of hypertension and without diabetes mellitus were recruited from the same population, and were sex-matched with experimental subjects. A polymorphism in intron 9 of the human renin gene was determined as the Mbo I restriction fragment length polymorphism (Mbo I-RFLP). There was no significant association between Mbo I-RFLP of the renin gene and predisposition to essential hypertension in Japanese (p>0.05, chi2=2.1). These results suggest that the Mbo I (+) allele of the renin gene does not increase the risk for hypertension in Japanese.

Candidate genes offer one approach to the identification of the genetic susceptibility to hypertension. A common gene variant of the low-density lipoprotein (LDL) receptor gene (LDLR) that affects plasma LDL metabolism within the normolipidaemic range, may be such a candidate gene. A common mutation of LDLR, C1773T, was associated with lipid metabolism such that the T1773 allele increased plasma LDL levels in a Caucasian population. The present study examined whether C1773T/LDLR was associated with essential hypertension in a Japanese population. Subjects with essential hypertension (EHT, n = 300) with a family history of hypertension, and controls (NT, n = 310, sex- and age-matched with EHT) were recruited from among out-patients at Osaka University Hospital. A C1773T substitution at codon 570 in LDLR was determined using PCR-Hinc II-RFLP. It was revealed that the C1773 allele was significantly more frequent (0.89) among hypertensive patients (chi2 = 9.58, P < 0.01) than normotensives (0.83), the calculated odds ratio being 1.7 (95% CI: 1.2-2.4). The effect of the T1773 allele on increasing cholesterol was significant in normotensives without antihyperlipidaemic medication, but not in hypertensives. After adjustments of confounding factors, the estimated odds ratio for hypertension in the subjects with C1773 homozygote increased to 2.1 (95% CI: 1.3-3.5), suggesting that this polymorphism is an independent risk factor for hypertension. Our results show that the C1773 mutant of LDLR increases susceptibility to hypertension, but not via hypercholesterolaemia.

A short, regiospecific synthesis of the naturally occurring anthrathiophene 1 from naphthazarin (7) is described.

The epsilon4 allele of apolipoprotein E (APOE) is reported to be a genetic risk factor of atherosclerosis through hyperlipidemia and late-onset Alzheimer's dementia. A recent report showed that a genetic variant (A -491T) in the promoter region of the APOE gene increases the risk of Alzheimer's disease. In the present study, we examined whether these APOE polymorphisms were genetically involved in essential hypertension. Japanese hypertensives (n=180) with a family history of hypertension and normotensive controls (n=195, sex and age matched with hypertensives) were recruited from the outpatients of Osaka University Hospital, and an informed consent to participate in the study was obtained from each person. APOE polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of the A -491 allele in hypertensives and normotensives were 0.98 and 0.97, respectively, and the TT/-491 genotype was not found in either group. No significant differences between hypertensives and normotensives were observed in allele frequencies in either APOE polymorphism; however, the mean diastolic blood pressure in normotensive subjects with AA/-491 was significantly higher than in the subjects with AT/-491 (p < 0.01). These results suggest that the presence of the APOE promoter polymorphism is not a major risk factor for hypertension but that it does have some minor effect on basal blood pressure variation.

Many unknown genetic factors are involved in the pathogenesis of hypertension. Recently, the reverse genetic approach revealed that some genetic variants, such as angiotensinogen, lipoprotein lipase, and alpha-adducin gene polymorphisms, increase the risk for hypertension. Both in rat and human, the genetic predisposition to hypertension was confirmed only for angiotensinogen and alpha-adducin genes. Adducin is a membrane cytoskeletal protein, which is thought to regulate sodium transport. Abnormalities of membrane sodium transport in the kidney play an important role in hypertension. A recent report by Cusi et al showed that the Trp allele of alpha-adducin polymorphism (Gly 460 Trp) is associated with an increased risk of hypertension in whites, which led us to carry out a case-control study to examine whether the same association is observed in the Japanese population. We recruited 170 hypertensive and 194 normotensive Japanese subjects and compared the genotype distribution of alpha-adducin 460 polymorphism between cases and controls and between whites and Japanese. Trp allele frequency of controls in the Japanese subjects was twice as high as in the whites. However, no association was observed between alpha-adducin polymorphism and hypertension. Furthermore, alpha-adducin 460 polymorphism was not associated with any clinical characteristics. Accordingly, we concluded that alpha-adducin 460 polymorphism is not a major genetic risk for hypertension in Japanese people.

A population-based follow-up study on the relationships between various environmental factors and risks of lung cancer has been conducted in Nagoya, Japan involving 24,489 inhabitants aged 40 or older. The baseline survey was conducted in 1985, using a self-recorded questionnaire. From a 10 year follow-up study, 161 cases with a newly diagnosed lung cancer (120 male cases and 41 female cases) were identified. Various environmental factors were related to the subsequent risk of lung cancer incidence. Causal relationship between smoking and lung cancer was noticed for current male smokers (RR = 5.72; 95% CI = 2.50-13.08) and for current female smokers (RR = 2.05%; 95% CI = 0.97-4.32). However, relative risks for other environmental factors were not statistically significant except increased risk for frequent coffee drinking in males (aRR = 2.02; 95% CI = 1.34-3.05) and decreased risk for frequent intake of green/yellow vegetables in females (aRR = 0.47; 95% CI = 0.23-0.94).

Werner syndrome (WS) is an autosomal recessive disease with a complex phenotype that is suggestive of accelerated aging. WS is caused by mutations in a gene, WRN, that encodes a predicted 1,432-amino-acid protein with homology to DNA and RNA helicases. Previous work identified four WS mutations in the 3' end of the gene, which resulted in predicted truncated protein products of 1,060-1,247 amino acids but did not disrupt the helicase domain region (amino acids 569-859). Here, additional WS subjects were screened for mutations, and the intron-exon structure of the gene was determined. A total of 35 exons were defined, with the coding sequences beginning in the second exon. Five new WS mutations were identified: two nonsense mutations at codons 369 and 889; a mutation at a splice-junction site, resulting in a predicted truncated protein of 760 amino acids; a 1-bp deletion causing a frameshift; and a predicted truncated protein of 391 amino acids. Another deletion is >15 kb of genomic DNA, including exons 19-23; the predicted protein is 1,186 amino acids long. Four of these new mutations either partially disrupt the helicase domain region or result in predicted protein products completely missing the helicase region. These results confirm that mutations in the WRN gene are responsible for WS. Also, the location of the mutations indicates that the presence or absence of the helicase domain does not influence the WS phenotype and suggests that WS is the result of complete loss of function of the WRN gene product.