Higher total white blood cell and neutrophil counts are associated with an increased risk of fatal stroke occurrence: the Guangzhou biobank cohort study.

BACKGROUND: Chronic inflammatory diseases are linked to an increased risk of stroke events. The white blood cell (WBC) count is a common marker of the inflammatory response. However, it is unclear whether the WBC count, its subpopulations and their dynamic changes are related to the risk of fatal stroke in relatively healthy elderly population. METHODS: In total, 27,811 participants without a stroke history at baseline were included and followed up for a mean of 11.5 (standard deviation = 2.3) years. After review of available records, 503 stroke deaths (ischaemic 227, haemorrhagic 172 and unclassified 104) were recorded. Cox proportional hazards regression was used to assess the associations between the WBC count, its subpopulations and their dynamic changes (two-phase examination from baseline to the 1st follow-up) and the risk of fatal all stroke, fatal ischaemic stroke and fatal haemorrhagic stroke. RESULTS: (i) Regarding the WBC count in relation to the risk of fatal stroke, restricted cubic splines showed an atypically U-curved association between the WBC count and the risk of fatal all stroke occurrence. Compared with those in the lowest WBC count quartile (< 5.3*10^9/L), the participants with the highest WBC count (> 7.2*10^9/L) had a 53 and 67% increased risk for fatal all stroke (adjusted hazard ratio [aHR] = 1.53, 95% confidence interval (CI) 1.16-2.02, P = 0.003) and fatal haemorrhagic stroke (aHR = 1.67, 95% CI 1.10-2.67, P = 0.03), respectively; compared with those in the lowest quartile (< 3.0*10^9/L), the participants with the highest NEUT count (> 4.5*10^9/L) had a 45 and 65% increased risk for fatal all stroke (aHR = 1.45, 95% CI 1.10-1.89, P = 0.008) and fatal ischaemic stroke (aHR = 1.65, 95%CI 1.10-2.47 P = 0.02), respectively. With the additional adjustment for C-reactive protein, the same results as those for all stroke and ischaemic stroke, but not haemorrhagic stroke, were obtained for the WBC count (4 ~ 10*10^9/L) and the NEUT count (the NEUT counts in the top 1% and bottom 1% at baseline were excluded). (ii) Regarding dynamic changes in the WBC count in relation to the risk of fatal stroke, compared with the stable group (- 25% ~ 25%, dynamic changes from two phases of examination (baseline, from September 1st, 2003 to February 28th, 2008; 1st follow-up, from March 31st 2008 to December 31st 2012)), the groups with a 25% increase in the WBC count and NEUT count respectively had a 60% (aHR = 1.60, 95% CI 1.07-2.40, P = 0.02) and 45% (aHR = 1.45, 95% CI1.02-2.05, P = 0.04) increased risk of fatal all stroke occurrence. CONCLUSIONS: The WBC count, especially the NEUT count, was associated with an increased risk of fatal all stroke occurrence. Longitudinal changes in the WBC count and NEUT count increase in excess of 25% were also associated with an increased risk of fatal all stroke occurrence in the elderly population.

Eukaryotic translation initiation factors and cancer.

Recent technological advancements have shown tremendous mechanistic accomplishments in our understanding of the mechanism of messenger RNA translation in eukaryotic cells. Eukaryotic messenger RNA translation is very complex process that includes four phases (initiation, elongation, termination, and ribosome recycling) and diverse mechanisms involving protein and non-protein molecules. Translation regulation is principally achieved during initiation step of translation, which is organized by multiple eukaryotic translation initiation factors. Eukaryotic translation initiation factor proteins help in stabilizing the formation of the functional ribosome around the start codon and provide regulatory mechanisms in translation initiation. Dysregulated messenger RNA translation is a common feature of tumorigenesis. Various oncogenic and tumor suppressive genes affect/are affected by the translation machinery, making the components of the translation apparatus promising therapeutic targets for the novel anticancer drug. This review provides details on the role of eukaryotic translation initiation factors in messenger RNA translation initiation, their contribution to onset and progression of tumor, and how dysregulated eukaryotic translation initiation factors can be used as a target to treat carcinogenesis.

Development of a novel nomogram for predicting prognosis of North Chinese with autoimmune cerebellar ataxia.

PURPOSE: The aim of this study was to develop a prognostic nomogram which could predict the prognosis of north Chinese patients with autoimmune cerebellar ataxia (ACA) after immunotherapy. METHODS: Patients with an initial diagnosis of ACA who accepted first-line immunotherapy at our hospital from March 2018 to May 2023 were retrospectively reviewed. Modified Rankin Scale (mRS) was used to evaluate neurological outcomes. According to the mRS scores after immunotherapy, patients with ACA were divided into good prognosis group (mRS 0-2) and poor prognosis group (mRS 3-6). The nomogram for poor prognosis of ACA patients were built based on logistic regression analysis. The validation of the prognostic model was evaluated by concordance index (C-index), calibration curves, and decision curve analyses (DCAs). RESULTS: A total of 86 patients with ACA who received immunotherapy at our hospital were included in this study. They were randomly divided into a training cohort (n = 60) and a validation cohort (n = 26) at a ratio of 7:3. Multivariate analyses revealed that that prognostic variables significantly related to the poor prognosis of ACA were age, elevated cerebrospinal fluid (CSF) albumin (ALB) and abnormal magnetic resonance imaging (MRI). The nomogram was constructed based on above 3 factors. The C-index of the nomogram was 0.935 (95% CI: 0.884-0.991) in the training set and 0.933 (95% CI: 0.763-0.994) in the validation set. The calibration plots for the nomogram showed that predictions of risk of poor prognosis were almost consistent with actual observations. The DCAs showed great clinical usefulness of the nomograms. CONCLUSION: We successfully developed a nomogram to predict poor prognosis for ACA patients using risk factors of age, elevated CSF-ALB and abnormal MRI.

Effects of rivaroxaban on activated clotting time in catheter ablation for atrial fibrillation in Chinese patients.

PURPOSE: It has been observed that patients on rivaroxaban require more heparin and frequent activated clotting time (ACT) monitoring throughout the catheter ablation of atrial fibrillation, but the strategy of heparin injection varies in different studies. We sought to examine the determinants of heparin dosage in Chinese patients on rivaroxaban. METHODS: We reviewed consecutive patients who received rivaroxaban before atrial fibrillation ablation and compared them to patients on no anticoagulant. The dosage of heparin required to achieve ACT > 300 s was evaluated. We then tested determinants of heparin dosage prospectively. RESULTS: There were 124 patients on rivaroxaban (R group) and 42 on no anticoagulant (NA group) in retrospective study. Heparin dosage required to achieve target ACT was 0.89 ± 0.01 mg/kg in R group and 0.60 ± 0.01 mg/kg in NA group, P < 0.05. The bolus heparin dosage required was 0.77 ± 0.01 mg/kg (96.1 ± 1.1 U/kg) when baseline ACT > 200 s. In the prospective study, 80/90(88.9%) of patients in R group and 79/90(87.8%) in NA group achieved an ACT > 300 s after initial bolus injection of heparin. The ACT 60 min after target ACT (ACT60) in R group was higher than that in NA group (287.5 ± 28.3 VS 238.9 ± 29.5, P < 0.05). Rivaroxaban was the only independent predictor of ACT60. There was no significant difference in ACT or heparin dosage in patients with different duration on or withdrawal of rivaroxaban. CONCLUSIONS: In patients undergoing atrial fibrillation ablation on rivaroxaban, the effective duration of heparin is prolonged and the procedural heparin requirement is significantly greater. Heparin dosage can be predicted by baseline ACT, but not influenced by duration on or withdrawal of rivaroxaban.

Curcumin exerts protective effects against hypoxia­reoxygenation injury via the enhancement of apurinic/apyrimidinic endonuclease 1 in SH­SY5Y cells: Involvement of the PI3K/AKT pathway.

Curcumin, a polyphenolic compound extracted from the plant Curcuma longa, has been reported to exert neuroprotective effects against cerebral ischemia reperfusion (I/R) injury. However, the mechanisms underlying these effects remain to be fully elucidated. Emerging evidence indicated that apurinic/apyrimidinic endonuclease 1 (APE1), a multifunctional enzyme, participates in neuronal survival against I/R injury. Therefore, the aim of the present study was to investigate whether curcumin alleviates oxygen­glucose deprivation/reperfusion (OGD/R)­induced SH­SY5Y cell injury, which serves as an in vitro model of cerebral I/R injury, by regulating APE1. The results revealed that curcumin increased cell viability, decreased LDH activity, reduced apoptosis and caspase­3 activity, downregulated the pro­apoptotic protein Bax expression and upregulated the anti­apoptotic protein Bcl­2 expression in SH­SY5Y cells subjected to OGD/R. Simultaneously, curcumin eliminated the OGD/R­induced decreases in APE1 protein and mRNA expression, as well as 8­hydroxy­2'­deoxyguanosine (8­OHdG) level and AP sites in SH­SY5Y cells. However, APE1 knockdown by siRNA transfection markedly abrogated the protective effects of curcumin against OGD/R­induced cytotoxicity, apoptosis and oxidative stress, as illustrated by the decreases in reactive oxygen species production and NADPH oxidase 2 expression, and the increase in superoxide dismutase activity and glutathione levels in SH­SY5Y cells. Furthermore, curcumin mitigated the OGD/R­induced activation of phosphatidylinositol 3­kinase/protein kinase B (PI3K/AKT) signaling pathway. Treatment with LY294002, an inhibitor of PI3K/AKT pathway activity, attenuated the protective effects of curcumin on cytotoxicity and apoptosis, and reversed the curcumin­induced upregulation of APE1 protein expression in SH­SY5Y cells subjected to OGD/R. Taken together, these results demonstrated that curcumin protects SH­SY5Y cells against OGD/R injury by inhibiting apoptosis and oxidative stress, and via enhancing the APE1 level and activity, promoting PI3K/AKT pathway activation.

Genetic diversity of the Chinese goat in the littoral zone of the Yangtze River as assessed by microsatellite and mtDNA.

The objective of this study was to assess the genetic diversity and population structure of goats in the Yangtze River region using microsatellite and mtDNA to better understand the current status of those goat genetic diversity and the effects of natural landscape in fashion of domestic animal genetic diversity. The genetic variability of 16 goat populations in the littoral zone of the Yangtze River was estimated using 21 autosomal microsatellites, which revealed high diversity and genetic population clustering with a dispersed geographical distribution. A phylogenetic analysis of the mitochondrial D-loop region (482 bp) was conducted in 494 goats from the Yangtze River region. In total, 117 SNPs were reconstructed, and 173 haplotypes were identified, 94.5% of which belonged to lineages A and B. Lineages C, D, and G had lower frequencies (5.2%), and lineage F haplotypes were undetected. Several high-frequency haplotypes were shared by different ecogeographically distributed populations, and the close phylogenetic relationships among certain low-frequency haplotypes indicated the historical exchange of genetic material among these populations. In particular, the lineage G haplotype suggests that some west Asian goat genetic material may have been transferred to China via Muslim migration.

A complete mitochondrial genome of Youzhou black-skin goat.

The Youzhou black-skin goat (Capra hircus), an indigenous breed of Chinese southwest. Here, we describe the complete mitochondrial genome sequence of Hechuan white goat. The mitogenome is 16,640 nt in length, consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes and a control region. As in other mammals, most mitochondrial genes are encoded on the heavy strand, except for ND6 and eight tRNA genes, which are encoded on the light strand. Its overall base composition is A: 33.5%, T: 27.3%, C: 26.1% and G: 13.1%. The complete mitogenome of the local subspecies of Hechuan white goat could provide an important data to further breed improvement and animal genetics resource conservation in China.

Complete mitochondrial genome of Hechuan white goat in China (Capra hircus).

The Hechuan white goat (Capra hircus), an indigenous of China. Here, we describe the complete mitochondrial genome sequence of Hechuan white goat. The mitogenome is 16,640 nt in length, consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes and a control region. As in other mammals, most mitochondrial genes are encoded on the heavy strand, except for ND6 and eight tRNA genes, which are encoded on the light strand. Its overall base composition is A: 33.5%, T: 27.3%, C: 26.1% and G: 13.1%. The complete mitogenome of the local subspecies of Hechuan white goat could provide an important data to further explore the breed improvement in Chinese goat.

A complete mitochondrial genome of Dazu Black goat.

Dazu Black goat is an indigenous goat genetic resource in Southwest of China. Here, we describe its complete mitochondrial genome sequence. The mitogenome is 16,641 bp in length, consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes and a control region. As in other mammals, most mitochondrial genes are encoded on the heavy strand, except for ND6 and eight tRNA genes, which are encoded on the light strand. Its overall base composition is A: 33.5%, T: 27.3%, C: 26.1% and G: 13.1%. The complete mitogenome of the indigenous goat could provide important data to further explore the taxonomic status of the subspecies and also provide a starting point for further phylogenetic studies.

Complete mitochondrial genome of Chuanzhong black goat in southwest of China (Capra hircus).

The Chuanzhong black goat (Capra hircus) is a breed native to southwest of China. Its complete mitochondrial genome is 16,641 nt in length, consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and a non-coding control region. As in other mammals, most mitochondrial genes are encoded on the heavy strand, except for ND6 and eight tRNA genes, which are encoded on the light strand. Its overall base composition is A: 33.5%, T: 27.3%, C: 26.1%, and G: 13.1%. The complete mitogenome of the Chinese indigenous breed of goat could provide a basic data for further phylogenetics analysis.

Characteristics of the mitochondrial genome of four native goats in China (Capra hircus).

Here, we describe the complete mitochondrial genome sequences of Jining Gray goat, Fushun black goat, Youzhou black-skin goat, and Hechuan white goat. The mitogenome of those four goats consisted of 16,640 nt, consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes and a control region. As in other mammals, most mitochondrial genes are encoded on the heavy strand, except for ND6 and eight tRNA genes, which are encoded on the light strand. The complete mitogenome of these four local breeds of Chinese native goats could provide an important data to further breed improvement and animal genetics resource conservation in China.

Possible induction of diabetes by treatment of hypertension with indapamide (with four case reports).

OBJECTIVE: To study therapy with indapamide impairing carbohydrate metabolism in essential hypertension patients and achieve earlier prevention, diagnoses and treatment of diabetes induced by indapamide. METHODS: Four cases of essential hypertension patients (1 male and 3 females) were observed through process of therapy with indapamide and laboratory investigations. RESULTS: After 4- to 14-month period of therapy with the combination of indapamide (2.5 mg/day) and fosinopril (10 mg/day) in three patients and 6-month period of monotherapy with indapamide (2.5 mg/day) in one patient, glucose levels of all patients increased and achieve criteria of diabetes diagnoses. After 3- to 13-month period of therapy without indapamide, glucose levels of all patients decreased and diabetes disappeared. CONCLUSION: Therapy with indapamide may induce diabetes in essential hypertension patients. After stopping indapamide, glucose tolerance impairing may be reversed.

[Genetic variation of six breeds of pigs by RAPD analysis].

The genetic variation of Meishan, Huainan, Tongcheng, Bamei, Hezuo and Largewhite pigs were analyzed by RAPD markers. Twenty-four single polymorphic primers were selected out of 276 primers by amplifying six pool DNA. The index of Shannon were 0.178672, 0.17781,0.15995, 0.14549,0.16949, 0.14159 respectively; Hpop was 0.16216, Hsp was 0.2534. The phylogenetic tree was constructed using NJ and UPGMA. The results indicated that the phenylogenetic relationship of the six pig breeds was consistent with their distribution.

Administration of dexamethasone protects mice against ischemia/reperfusion induced renal injury by suppressing PI3K/AKT signaling.

Dexamethasone (DEX), a ligand for glucocorticoid receptor (GR), has long been used in the clinical practice due to its anti-inflammatory and immunosuppressive properties. Given that ischemia/reperfusion (IR)-induced renal injury is featured by the excessive immune response; the current study is therefore designed to address the impact of dexamethasone on IR-induced renal injury, a common disorder in the clinical settings. Precondition of mice with 4 mg/kg of dexamethasone significantly attenuated IR-induced injury as manifested by the improved renal function along with ameliorated pathological changes and suppressed inflammatory infiltration. Mechanistic studies revealed that dexamethasone promotes GR activation, and by which it attenuates the signals for PI3K/AKT activation. Attenuated PI3K/AKT signaling thus suppresses inflammatory response which then protects kidneys from IR-induced injury. All together, our data support that dexamethasone could be a good alternative therapy for prevention and treatment of IR-induced renal injury in the clinical practice.

Solid dynamic models for analysis of stress and strain in human hearts.

This paper proposes a solid model based on four-dimensional trivariate B-spline for strain and stress analysis of ventricular myocardium. With a series of processing steps in the four-dimensional medical images, the feature points of ventricular inner and outer wall are obtained. A B-spline surface is then used to build the dynamic deformation model of the myocardial walls. With such a surface model, a hexahedron control mesh can be constructed by sweeping the cloud data, and the ventricular solid model is built by fitting the trivariate B-spline parameters. Based on these models, a method of isogeometric analysis can be applied to calculate the stress and strain continuously distributed in the ventricle. The model is represented smoothly in the cylindrical coordinate system and is easy to measure myocardium dynamics for finding abnormal motion. Experiments are carried out for comparing the stress and strain distribution. It is found that the solid model can determine ventricular dynamics which can well reflect the deformation distribution in the heart and imply early clues of cardiac diseases.

NNAT and DIRAS3 genes are paternally expressed in pigs.

Although expression and epigenetic differences of imprinted genes have been extensively characterised in man and the mouse, little is known on livestock species. In this study, the polymorphism-based approach was used to detect the imprinting status of NNAT and DIRAS3 genes in five heterozygous pigs (based on SNP) of Large White and Meishan F(1) hybrids. The results show that both genes were paternally expressed in all the tested tissues (heart, liver, spleen, lung, kidney, stomach, small intestine, skeletal muscle, fat, uterus, ovary and pituitary). In addition, the NNAT gene had two transcripts in all tested tissues, which is consistent with its counterpart in man and cattle.