[Theoretical models for influenza vaccination behavior at the individual level].

Influenza imposes a significant disease burden on society and individuals annually, and influenza vaccination is considered a significant public health measure to prevent influenza and reduce influenza-related severe disease and death. The low influenza vaccination rate in China is partly due to certain factors affecting the willingness and behavior of individuals to receive them. Scientific research and targeted interventions on these factors can effectively improve the vaccination situation. Commonly used individual-level theoretical models for influenza vaccination behavior include the health belief model, protection motivation theory, and theory of planned behavior. This study reviews theoretical models commonly employed in researching influenza vaccination willingness and behavior. An overview of these practical applications and challenges models is presented to provide references for relevant research and intervention programs in China.

[The optimal examination duration for the detection of epileptiform discharge in outpatient video-electroencephalography].

Objective: To determine the optimal examination duration by evaluating the detection rate of epileptiform discharges (EDs) with different examination duration of video-electroencephalography (EEG) in outpatients. Methods: Patients with EDs who underwent 4-hour EEG examination from Xuanwu Hospital, Capital Medical University from October 2020 to November 2021 were retrospectively enrolled, and the detection rates of EDs were calculated with examination duration of 0-0.5 h, 0-1 h, 0-2 h, 0-3 h, and 0-4 h (group A, B, C, D and E), respectively. For each patient, EDs in each hour (group H1, group H2, group H3, group H4) were counted, and the standardized amount of EDs was calculated. For each patient, EDs in wakefulness, drowsiness, non-rapid eye movement-Ⅰ (NREM-Ⅰ), NREM-Ⅱ and NREM-Ⅲ were counted, and the standardized amount of EDs in each state was calculated. Meanwhile, the sleep duration per hour of each patient was also counted (group H1', group H2', group H3', group H4'). The Wilcoxon paired test was used for intergroup comparison to determine the optimal examination duration. Results: A total of 80 patients were enrolled, and aged [M(Q1, Q3)]31 (21, 39) years (range: 5-68 years). There were 38 males and 42 females. The detection rate of EDs was 42.5% (34/80) in group A, 81.3% (65/80) in group B, and 100.0% (80/80) in group C, group D and group E, respectively. The standardized amount of EDs of H1, H2, H3 and H4 was 24.8% (7.8%, 44.2%), 41.5% (25.9%, 63.3%), 15.1% (1.3%, 27.8%) and 1.3% (0, 14.5%), respectively. The standardized amount of EDs of H2 was significantly higher than that of H1, H3 and H4 (all P<0.05). The standardized amount of EDs in wakefulness, drowsiness, NREM-Ⅰ, NREM-Ⅱ and NREM-Ⅲ were 9.6% (0, 28.2%), 3.6% (0, 16.9%), 3.3% (0, 11.8%), 47.3% (21.9%, 72.5%) and 0 (0, 11.5%), respectively. The standardized amount of EDs in NREM-Ⅱ was significantly higher than that in wakefulness, drowsiness, NREM-Ⅰ and NREM-Ⅲ (all P<0.05). The sleep duration in the group of the H1', H2', H3' and H4' was 13.6 (2.5, 23.6), 35.8 (16.5, 54.2), 14.5(0, 34.7) and 0 (0, 14.6) minutes, respectively. The sleep duration in the group of the H2' group was significantly longer than that in the group of H1', H3' and H4' (all P<0.05). Conclusion: The study recommends 2 hours video-EEG in outpatients, which not only ensures the detection rate of EDs, but also facilitates patient cooperation and optimizes the allocation of medical resources.

A SNP in PLAG1 is associated with body height trait in Chinese cattle.

Stature is an important quantitative trait for cattle performance, which influences herd productivity. Previous studies have reported that an SNP (AC_000171.1:g.25015640G>T, rs109815800) in Pleomorphic adenoma gene 1 (PLAG1) on chromosome 14 (CHR14) is associated with bovine stature. To validate whether rs109815800 is associated with the body height of Chinese cattle, we carried out an association analysis using 558 adult cattle samples from seven populations. Then, 1038 samples from 38 Chinese cattle breeds were used to show the geographical distribution of this variant in China. The results showed that the Q allele (G allele) increased the height of cattle. Furthermore, the frequencies of Q allele in Chinese native breeds tend to decrease from northern China to southern China, and the frequency of Q allele in two Chinese beef cattle breeds is much higher than that in another 36 Chinese local cattle breeds. Our data suggest that the prevalence of the Q allele is correlated with latitude in China.

Genetic diversity of Chinese cattle revealed by Y-SNP and Y-STR markers.

With its vast territory and complex natural environment, China boasts rich cattle genetic resources. To gain the further insight into the genetic diversity and paternal origins of Chinese cattle, we analyzed the polymorphism of Y-SNPs (UTY19 and ZFY10) and Y-STRs (INRA189 and BM861) in 34 Chinese cattle breeds/populations, including 606 males representative of 24 cattle breeds/populations collected in this study as well as previously published data for 302 bulls. Combined genotypic data identified 14 Y-chromosome haplotypes that represented three haplogroups. Y2-104-158 and Y2-102-158 were the most common taurine haplotypes detected mainly in northern and central China, whereas the indicine haplotype Y3-88-156 predominates in southern China. Haplotypes Y2-108-158, Y2-110-158, Y2-112-158 and Y3-92-156 were private to Chinese cattle. The population structure revealed by multidimensional scaling analysis differentiated Tibetan cattle from the other three groups of cattle. Analysis of molecular variance showed that the majority of the genetic variation was explained by the genetic differences among groups. Overall, our study indicates that Chinese cattle retain high paternal diversity (H = 0.607 ± 0.016) and probably much of the original lineages that derived from the domestication center in the Near East without strong admixture from commercial cattle carrying Y1 haplotypes.

Comprehensive analysis of the mitochondrial DNA diversity in Chinese cattle.

Complete mitochondrial DNA D-loop sequences of 1105 individuals were used to assess the diversity of maternal lineages of cattle populations in China. In total, 250 taurine and 88 zebu haplotypes were identified. Five main haplogroups-T1a, T2, T3, T4 and T5-were identified in Bos taurus, whereas Bos indicus harbored two haplogroups-I1 and I2. Our results suggest that the distribution of T1a in Asia was concentrated mainly in the northeast region (northeast China, Korea and Japan); haplogroups T2, T3 and T4 were predominant in Chinese cattle; and T5 was sporadically detected in Mongolian and Pingwu cattle. In contrast to the widespread presence of I1, I2 was distributed only in southwestern China (Yunnan-Guizhou Plateau and the Tibet Autonomous Region) and Xinjiang Uygur Autonomous Region. This is the first time that all five taurine haplogroups and two zebu haplogroups have been found in Mongolian cattle. In addition, eight individuals in Tibetan cattle carried the Bos grunniens mtDNA type. The high mtDNA diversity (H = 0.904 ± 0.008) and the weak genetic structure among the 57 Chinese cattle breeds/populations are consistent with their complex historical background, migration route and ecological environment.

Longissimus dorsi muscle transcriptomic analysis of Yunling and Chinese simmental cattle differing in intramuscular fat content and fatty acid composition.

Intramuscular fat (IMF) content and fatty acid (FA) composition vary significantly across beef cattle breeds, which play an important role in taste and nutritional value. However, the molecular mechanisms underlying these phenotypic differences remain unknown. The present study compared meat quality traits between Yunling cattle and Chinese Simmental cattle. Yunling cattle showed a lower IMF content and proportion of monounsaturated fatty acids (MUFA), as well as higher proportions of saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), and short-chain fatty acids (sc-FA) in the longissimus dorsi (LD) muscle than Chinese Simmental cattle. To further identify the candidate genes and pathways responsible for these phenotypic differences, the transcriptome of LD muscle from the two breeds were measured using RNA-seq. A total of 1347 differentially expressed genes were identified. The major metabolic pathways that were differentially modulated were lipolysis and glycometabolism. Yunling cattle showed a higher expression of lipolysis genes (ALDH9A1, ACSL5, ACADM, ACAT2, ACOT2) and a lower expression of genes related to glycometabolism (PGM1, GALM, PGM1, GPI, LDHA). This research identified candidate genes and pathways for IMF content and FA composition in the LD muscle of beef cattle, which may facilitate the design of new selection strategies to improve meat quality.

Liver Transplantation Using Donation After Brain and Cardiac Death: A Single-Center Experience in China.

BACKGROUND: Liver transplantation (LTx) using donation after brain and cardiac death (DBCD) has increased steadily in China. The aims of this study were to evaluate the outcomes of DBCD LTx and to assess its feasibility to expand the donor pool. METHODS: We retrospectively analyzed the clinical characteristics of DBCD donors and recipients, survival of allografts and recipients, and prognostic factors in DBCD LTx recipients from March 2010 to December 2014 in our institution. RESULTS: DBCD LTx (n = 102) were performed in our institution during the research period, and the successful donation rate was 26.0%. Mean warm ischemia time and cold ischemia time were 14.39 minutes and 5.29 hours, respectively. The overall and biliary complication rates were 45.1% and 16.7%, respectively. Donor age (P = .043), intra-operative blood loss (P = .048), and operation time (P = .045) were significantly different between the complication and non-complication groups. The 1-, 2-, and 3-year survival rates of patients and grafts were 88.0%, 84.6%, 84.6%, and 85.7%, 78.6%, and 78.6%, respectively. The 1- and 2-year overall survival rates of hepatocellular carcinoma patients were 91.9% and 80.5%, respectively whereas the recurrence-free survival rates were 84.9% and 77.2%, respectively. The patient and graft survival rates were not statistically different between the <55-year and ≥55 year groups, but complication rate was higher in the older group than in the younger group (P = .003). CONCLUSIONS: The outcome of DBCD LTx is favorable in our institution, with careful donor and recipient selection and careful peri-operative management. DBCD is an optimized solution for organ shortage in today's China.

Tumor existence and tumor size as prognostic factors in hepatitis B virus-related cirrhosis patients who underwent liver transplantation.

BACKGROUND: Hepatitis B virus (HBV)-related chronic liver disease is one of the most common indications for liver transplantation (LT). Patient data in our unit were collected to evaluate the impact of liver tumor on outcomes in patients with HBV-related cirrhosis who underwent LT. METHODS: HBV transplantation patients in our hospital from August 2002 to March 2012 were analyzed and compared according to LT indications: decompensated cirrhosis (DEC) or hepatocellular carcinoma (HCC). For HCC patients, receiver operating characteristic (ROC) curve analysis was used to determine the cutoff tumor size for prognosis, namely the maximum tumor diameter. According to the cutoff size, patients were divided into 2 groups: large-size HCC and small-size HCC. The correlations among other clinicopathologic factors were also investigated. Potential prognostic factors were evaluated with the use of Cox proportional hazards model analysis. RESULTS: The 1-, 3-, and 5-year overall survival rates of the 111 HBV-related patients were 76.2%, 43.2%, and 32.9%, respectively. Patients with HCC had significantly poorer overall survival than those with only DEC (P < .05). The mean tumor size was 5.97 cm, and ROC analysis indicated that the cutoff tumor size for prognosis was 4.25 cm, with sensitivity and specificity of 62.8% and 81.0%, respectively (area under the ROC curve, 0.760; 95% CI, 0.644-0.877; P < .001). According to this cutoff point, 31 patients had large tumor size (≥ 4.25 cm) and 33 had small tumor size (<4.25 cm). Patients with small tumor size had significantly better overall survival than those with large tumor size (P < .05). Univariate analysis showed that only the tumor size (risk ratio, 1.14; P < .001) was significantly associated with the overall survival. CONCLUSIONS: Tumor existence and tumor size are prognostic factors in HBV-related cirrhosis. With the use of a tumor size cutoff value of 4.25 cm, patients with large-size tumors have significantly poorer overall survival than those with small-size tumors.

A new high-frequency allele of the BM2113 locus in the Yunnan mithun population.

The BM2113 locus was amplified in Yunnan mithun (Bos frontalis) from the southwest mountains of China. It showed a high degree of polymorphism with a total of 12 alleles. The 121-bp polymorphic allele of the BM2113 locus that accounted for 37.1% of homozygotes was the predominant allele with a frequency of 58.57%, identified as mithun-specific for Bos species in Yunnan mithun. The polymorphism information content value was high with a mean of 0.6170, the expected and observed heterozygosity was moderate with values of 0.6427 and 0.6000, respectively, and the BM2113 locus was under Hardy-Weinberg equilibrium (P = 0.2897) in the Yunnan mithun population. This study elucidated the genetic diversity, multi-origin, specific alleles, and characterization of mithun.

Association of bovine Toll-like receptor 4 with tick infestation rates and blood histamine concentration.

We investigated a possible association between bovine Toll-like receptor 4 (TLR4) and resistance to tick infestation in 103 cattle, including BMY cattle (1/2 Brahman, 1/4 Murray Grey, and 1/4 Yunnan Yellow cattle), Brahman, and Red Angus grazing on improved pasture. The tick infestation weight and number of Rhipicephalus microplus and the blood histamine concentration were measured and compared with those of 32 Chinese Holsteins and 30 Simmentals. A 228-bp fragment was amplified and sequenced to analyze the polymorphisms of the TLR4 gene. After SSCP and sequencing analysis, 4 SNPs, i.e., 535(A>C), 546(T>C), 605(T>A), and 618(G>C), were identified, corresponding to GenBank accession Nos. AY297041 and NW_003104150; the latter two SNPs caused Leu→Gln and Gln→His substitutions, respectively. Genotype AA was completely predominant in the Chinese Holstein and Simmental; genotypes AA and AB were detected in Red Angus, while genotypes AA, AB, BB, and BC were detected in Brahman and in BMY cattle. A negative correlation was identified between blood histamine concentration and number of tick infestation; in BMY cattle this negative association was significant. The tick infestation in cattle with genotype BB was significantly lower than in those with genotype AA. Blood histamine concentration in cattle with genotype BB was significantly higher than in those with genotype AA. The TLR4 gene mutation could affect the blood histamine level and activate the immune reaction after tick infestation. Allele B has potential as a molecular marker for tick-resistance originated from Zebu cattle for use in cattle breeding programs.

Genetic diversity analysis of BMY cattle based on microsatellite DNA markers.

BMY cattle (1/2 Brahman, 1/4 Murray Grey and 1/4 Yunnan Yellow cattle) has been inter se breeding since 1980s. Genetic diversity of BMY cattle was extensively investigated using 16 microsatellite markers. A total of 130 microsatellite alleles and high allele size variance were detected. All loci displayed high genetic diversity with overall mean of N(a) = 8.13, PIC = 0.7224 and H(e) = 0.7666, which were higher than those of many other beef breeds. The allele-sharing neighbour-joining tree clearly displayed the new genotypic combinations and the minglement from both BMY cattle and Brahman. The results provided the genetic information to match the standards of new beef breed in South China.

Karyotype analysis of mithun (Bos frontalis) and mithun bull x Brahman cow hybrids.

We examined the cytogenetics of mithun (Bos frontalis), a domesticated version of the Asian gaur, and hybrids (F(1) generation) produced by artificial insemination of Brahman cows (Bos indicus) with mithun semen. Reproductive potential was also examined in the F(1) generation and a backcrossed heifer for utilization of heterosis. Metaphase chromosome spreads were examined by conventional staining and fluorescence in situ hybridization hybridized with the entire chromosome 1 of mithun as a specific probe. Chromosome 1 of mithun was found to be equivalent to Bos taurus chromosomes 2 and 28. The karyotype of the female mithun (N = 4) comprised 58 chromosomes, including 54 acrocentric and four large submetacentric chromosomes, without the four acrocentric chromosomes found in the domesticated species B. indicus. However, one of the four female mithuns with a normal mithun phenotype had an abnormal karyotype (2n = 59), indicating introgression from B. taurus or B. indicus. The F(1) karyotypes (N = 6, 3♂3♀) of the mithun bull × Brahman cow cross had 2n = 59, intermediate between their parents; they were consistent heterozygous carriers with a centric fusion involving rob(2;28), as expected. Two pronounced red signals were seen in the mithun karyotypes, three red signals in the mithun × Brahman hybrids, and four red signals in the Brahman cattle, in good agreement with centric fusion of bovine rob(2;28). The female backcross hybrid (N = 1) with 2n = 59 had a similar chromosome configuration to the F(1) karyotypes and had rob(2;28). Such female backcross hybrids normally reproduce; however, the F(1) bulls (N = 3) had not yet generated normal sperm at 24 months.

Understanding stem cell differentiation through self-organization theory.

The mechanism underling stem cells' key property, the ability to either divide into two replicate cells or a replicate and a differentiated daughter, still is not understood. We tested a hypothesis that stem cell asymmetric division/differentiation is spontaneously created by the coupling of processes within each daughter and the resulting biochemical feedbacks via the exchange of molecules between them during mitotic division. We developed a mathematical/biochemical model that accounts for dynamic processes accompanying division, including signaling initiation and transcriptional, translational and post-translational (TTP) reactions. Analysis of this model shows that it could explain how stem cells make the decision to divide symmetrically or asymmetrically under different microenvironmental conditions. The analysis also reveals that a stem cell can be induced externally to transition to an alternative state that does not have the potentiality to have the option to divide symmetrically or asymmetrically. With this model, we initiated a search of large databases of transcriptional regulatory network (TRN), protein-protein interaction, and cell signaling pathways. We found 12 subnetworks (motifs) that could support human stem cell asymmetric division. A prime example of the discoveries made possible by this tool, two groups of the genes in the genetic model are revealed to be strongly over-represented in a database of cancer-related genes.

Approaches to discovering drugs that regulate E3 ubiquitin ligases.

The ubiquitin-proteasome system (UPS) plays an essential role in a wide variety of cell regulatory signaling pathways. The clinical effectiveness of the proteasome inhibitor Velcade in the treatment of several human cancers underscores the importance of the UPS as a novel target area for pharmaceutical intervention. E3 ubiquitin ligases are key enzyme complexes that regulate and determine the ubiquitination of specific substrates, whose abnormal regulation has been implicated in multiple disease phenotypes. Targeting a selective E3 ligase may allow specific manipulation of distinct pathways and eventually lead to a better therapeutic index with reduced nonspecific side effects. Here, we aim to discuss the challenges of interfering with small molecules in this target class, as well as current strategies and progress in E3 ligase drug discovery.

Hydrogen sulfide: neurochemistry and neurobiology.

Current evidence suggests that hydrogen sulfide (H2S) plays an important role in brain functions, probably acting as a neuromodulator as well as an intracellular messenger. In the mammalian CNS, H2S is formed from the amino acid cysteine by the action of cystathionine beta-synthase (CBS) with serine (Ser) as the by-product. As CBS is a calcium and calmodulin dependent enzyme, the biosynthesis of H2S should be acutely controlled by the intracellular concentration of calcium. In addition, it is also regulated by S-adenosylmethionine which acts as an allosteric activator of CBS. H2S, as a sulfhydryl compound, has similar reducing properties as glutathione. In neurons, H2S stimulates the production of cAMP probably by direct activation of adenylyl cyclase and thus activate cAMP-dependent processes. In astrocytes, H2S increases intracellular calcium to an extent capable of inducing and propagating a "calcium wave", which is a form of calcium signaling among these cells. Possible physiological functions of H2S include potentiating long-term potentials through activation of the NMDA receptors, regulating the redox status, maintaining the excitatory/inhibitory balance in neurotransmission, and inhibiting oxidative damage through scavenging free radicals and reactive species. H2S is also involved in CNS pathologies such as stroke and Alzheimer's disease. In stroke, H2S appears to act as a mediator of ischemic injuries and thus inhibition of its production has been suggested to be a potential treatment approach in stroke therapy.

ELISA system for detection of immune responses to FVIII: a study of 246 samples and correlation with the Bethesda assay.

Inhibitors of FVIII are usually IgG polyclonal antibodies that develop as alloimmune responses in patients with congenital haemophilia A or as autoimmune responses resulting in acquired haemophilia. Their recognition can be difficult, especially when the titre is low. Furthermore, results from a Bethesda assay often require several days as samples are referred to a specialty laboratory. The aim of this study is to assess the utility of an ELISA system for detecting immune responses to FVIII. A total of 246 plasma samples submitted from 176 individuals with immune responses to FVIII, as verified with the Bethesda assay, and samples from 50 control subjects were tested for the presence of FVIII-specific IgG using an ELISA-based assay. Paired sera from 18 of the patients were also tested by the ELISA. Of the 246 samples that were positive for a FVIII inhibitor by the Bethesda assay, 235 (95.5%) were also positive by ELISA. The regression coefficient, using Log BU was r = 0.82. The correlation data were strengthened when 27 inhibitor samples were diluted further. There was a strong correlation between ELISA results for the 18-paired serum and plasma samples (r = 0.99). There is a strong correlation between the ELISA and Bethesda methods in detecting immune responses to FVIII. The ELISA provides rapid screening that could be available well in advance of confirmation by the Bethesda assay.

Alternative method to construct equilibrium distribution functions in lattice-Boltzmann method simulation of inviscid compressible flows at high Mach number.

A method is proposed to construct an equilibrium density distribution function in the simulation of compressible flows at high Mach number by the lattice-Boltzmann method. In this method, the conventional Maxwellian distribution function is replaced by a circular function which is very simple and satisfies all needed statistical relations to recover the compressible Navier-Stokes equations. The circular function is then distributed to the lattice velocity directions by Lagrangian interpolation in such a way that all the needed statistical relations are exactly satisfied when the integral in the phase space is replaced by the summation in the context of the lattice-Boltzmann (LB) method. In this framework, the equilibrium distribution functions and the associated lattice velocity model can be derived naturally without assuming specific forms. Two LB models with adjustable specific heat ratio, respectively, for one-dimensional (1D) and two-dimensional (2D) compressible flows are shown in the paper. Some test cases of compressible flows with strong shock waves are simulated to validate the present approach. Excellent results are obtained. Note that in the simulation, the total variation diminishing (TVD) scheme was used to capture the discontinuity with coarse mesh.

Cancer onset and progression: a genome-wide, nonlinear dynamical systems perspective on onconetworks.

It is hypothesized that the many human cell types corresponding to multiple states is supported by an underlying nonlinear dynamical system (NDS) of transcriptional regulatory network (TRN) processes. This hypothesis is validated for epithelial cells whose TRN is found to support an extremely complex array of states that we term a "bifurcation nexus", for which we introduce a quantitative measure of complexity. The TRN used is constructed and analyzed by integrating a database of TRN information, cDNA microarray data analyzers, bioinformatics modules, a transcription/translation/post-translation kinetic model, and NDS analysis software. Results of this genome-wide approach suggest that a cell can be induced to persist in one state or to transition between distinct states; apparently irreversible transitions can be reversed when the high dimensional space of extracellular and intracellular parameters is understood. As conditions change, certain cellular states (cell lines) are no longer supported, new ones emerge, and transitions (cell differentiation or death) occur. The accumulation of simulated point mutations (minor changes which individually are insignificant) lead to occasional dramatic transitions. The genome-wide scope of many of these transitions is shown to arise from the cross-linked TRN structure. These notions imply that studying individual oncogenes may not be sufficient to understand cancer; rather, "onconetworks" (subsets of strongly coupled genes supporting multiple cell states) should be considered. Our approach reveals several epithelial onconetworks, each involving oncogenes and anti-tumor and supporting genes.