Lever-enabled milli-Newton mechanical force detection via a microbottle resonator.

We demonstrate a milli-Newton mechanical force sensor based on a whispering gallery mode microbottle resonator (MBR). A lever model is established by coupling the MBR with a tapered fiber, whose ratio of load arm to effort arm (RLE) is flexibly adjusted to enlarge the detection range. The mechanical force is induced by attaching a capillary on the MBR stem and applying the downward displacement, which deforms the MBR's radius and thus shifts the resonance wavelength. The dependence of the capillary displacement on the mechanical force is theoretically deduced and verified. Experimentally, the sensors with different RLEs are built, and the maximum sensitivity of -10.48 pm/mN with a resolution of 40 µN is obtained. The achieved detection range is 0-4 mN, which depends on the capillary displacement and RLE of the lever. With the merits of easy fabrication and flexible structure, the proposed sensor shows great potential in biomedical and structural health monitoring.

Abnormal function of EPHA2/p.R957P mutant in congenital cataract.

AIM: To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity. METHODS: A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited. Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals. Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery. The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software. Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2 (EPHA2). Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins. The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assay, respectively. The cell migration was analyzed by wound healing assay. Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo. RESULTS: A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif (SAM) domain of EPHA2. Functional studies demonstrated the variant's impact: reduced EPHA2 protein expression, altered subcellular localization, and disrupted interactions with other lens membrane proteins. This mutant notably enhanced human lens epithelial cell migration, and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast (DIC) optics. CONCLUSION: Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.

An S-locus F-box protein as pollen S determinant targets non-self S-RNase underlying self-incompatibility in Citrus.

Self-incompatibility (SI) is a crucial mechanism that prevents self-fertilization and inbreeding in flowering plants. Citrus exhibits SI regulated by a polymorphic S-locus containing an S-RNase gene and multiple S-locus F-box (SLF) genes. It has been documented that S-RNase functions as the pistil S determinant, but there is no direct evidence that the SLF genes closely linked with S-RNase function as pollen S determinants in Citrus. This study assembled the genomes of two pummelo (Citrus grandis) plants, obtained three novel complete and well-annotated S-haplotypes, and isolated 36 SLF or SLF-like alleles on the S-loci. Phylogenetic analysis of 138 SLFs revealed that the SLF genes were classified into 12 types, including six types with divergent or missing alleles. Furthermore, transformation experiments verified that the conserved S6-SLF7a protein can lead to the transition of SI to self-compatibility by recognizing non-self S8-RNase in 'Mini-Citrus' plants (S7S8 and S8S29, Fortunella hindsii), a model plant for citrus gene function studies. In vitro assays demonstrated interactions between SLFs of different S haplotypes and the Skp1-Cullin1-F-box subunit CgSSK1 protein. This study provides direct evidence that SLF controls the pollen function in Citrus, demonstrating its role in the 'non-self recognition' SI system.

[Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China]. / ç”˜è‚ƒåœ°åŒºé—ä¼ ä»£è°¢ç— ç–¾ç— è°±åŠè‡´ç— åŸºå› åˆ†æž.

OBJECTIVES: To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China. METHODS: A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination. RESULTS: A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance. CONCLUSIONS: This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Fluorinated hydrogel nanoparticles with regulable fluorine contents and T2 relaxation times as 19F MRI contrast agents.

Medical imaging contrast agents that are able to provide detailed biological information have attracted increasing attention. Among the new emerging imaging contrast agents, 19F magnetic resonance imaging contrast agents (19F MRI CAs) are extremely promising for their weak background disturbing signal from the body. However, to prepare 19F MRI CAs with a long T2 relaxation time and excellent biocompatibility in a simple and highly effective strategy is still a challenge. Herein, we report a new type of 19F MRI hydrogel nanocontrast agents (19F MRI HNCAs) synthesized by a surfactant-free emulsion polymerization with commercial fluorinated monomers. The T2 relaxation time of 19F MRI HNCA-1 was found to be 25-40 ms, guaranteeing its good imaging ability in vitro. In addition, according to an investigation into the relationship between the fluorine content and 19F MRI signal intensity, the 19F MRI signal intensity was not only determined by the fluorine content in 19F MRI HNCAs but also by the hydration microenvironment around the fluorine atoms. Moreover, 19F MRI HNCAs demonstrated excellent biocompatibility and imaging capability inside cells. The primary exploration demonstrated that 19F MRI HNCAs as a new type of 19F MRI contrast agent hold potential for imaging lesion sites and tracking cells in vivo by 19F MRI technology.

More Than Just Static: Dynamic Functional Connectivity Changes of the Thalamic Nuclei to Cortex in Parkinson's Disease With Freezing of Gait.

Background: The thalamus is not only a key relay node of the thalamocortical circuit but also a hub in the regulation of gait. Previous studies of resting-state functional magnetic resonance imaging (fMRI) have shown static functional connectivity (FC) between the thalamus and the cortex are disrupted in Parkinson's disease (PD) patients with freezing of gait (FOG). However, temporal dynamic FC between the thalamus and the cortex has not yet been characterized in these patients. Methods: Fifty PD patients, including 25 PD patients with FOG (PD-FOG) and 25 PD patients without FOG (PD-NFOG), and 25 healthy controls (HC) underwent resting-state fMRI. Seed-voxel-wise static and dynamic FC were calculated between each thalamic nuclei and other voxels across the brain using the 14 thalamic nuclei in both hemispheres as regions of interest. Associations between altered thalamic FC based on significant inter-group differences and severity of FOG symptoms were also examined in PD-FOG. Results: Both PD-FOG and PD-NFOG showed lower static FC between the right lateral posterior thalamic nuclei and right inferior parietal lobule (IPL) compared with HC. Altered FC dynamics between the thalamic nuclei and several cortical areas were identified in PD-FOG, as shown by temporal dynamic FC analyses. Specifically, relative to PD-NFOG or HC, PD-FOG showed greater fluctuations in FC between the left intralaminar (IL) nuclei and right IPL and between the left medial geniculate and left postcentral gyrus. Furthermore, the dynamics of FC between the left pulvinar anterior nuclei and left inferior frontal gyrus were upregulated in both PD-FOG and PD-NFOG. The dynamics of FC between the right ventral lateral nuclei and left paracentral lobule were elevated in PD-NFOG but were maintained in PD-FOG and HC. The quantitative variability of FC between the left IL nuclei and right IPL was positively correlated with the clinical scales scores in PD-FOG. Conclusions: Dynamic FC between the thalamic nuclei and relevant associative cortical areas involved in sensorimotor integration or cognitive function was disrupted in PD-FOG, which was reflected by greater temporal fluctuations. Abnormal dynamic FC between the left IL nuclei of the thalamus and right IPL was related to the severity of FOG.

Changes of proportions of circulating lymphocyte subsets in cancer patients after chemotherapy.

BACKGROUND: It remains unknown how chemotherapy affects circulating lymphocyte subsets and whether the pattern of change is related to prognosis in cancer patients. METHODS: Cancer patients who received chemotherapy between 2018/03/01 and 2019/12/31 were enrolled from the Hefei Cancer Hospital, Chinese Academy of Sciences. Peripheral blood samples were collected before and 3 weeks after the start of chemotherapy, and the proportions of T cells (CD3+), helper T cells (CD3+CD4+), cytotoxic T cells (CD3+CD8+), B cells (CD19+), and Natural killer (NK) cells (CD3-CD56+) were examined by flow cytometry. Multivariable logistic regression analysis was employed to explore risk factors associated with overall survival within 12 months after the start of chemotherapy. RESULTS: A total of 167 patients with cancer were included in the analysis, including 14 cases of cervical cancer, 18 cases of breast cancer, 33 cases of gastric cancer, 48 cases of lung cancer, 21 cases of colorectal cancer, and 33 cases of esophageal cancer. The proportion of T cells (72.58%±10.44% vs. 80.67%±11.63%, P<0.001) and cytotoxic T cells (25.38%±8.87% vs. 39.20%±12.26%, P<0.001) significantly increased, while the proportion of helper T cells (45.58%±10.19% vs. 41.98%±10.47%, P<0.001), B cells (15.10%±5.23% vs. 11.29%±5.60%, P<0.001), and NK cells (19.33%±7.54% vs. 18.28%±7.62%, P<0.001) significantly decreased at 3 weeks after chemotherapy when compared to baseline levels. The overall mortality rate was 14.97% (25/167) within 1 year after the start of chemotherapy. Patients who survived showed a significantly less increase in cytotoxic T cells (13.38%±8.28% vs. 17.28%±7.97%, P=0.030) and less decrease in B cells (-3.58%±2.81% vs. -5.29%±3.03%, P=0.006) when compared to non-survivors. Greater decreases in helper T cells (OR 0.81, 95% CI, 0.68-0.96) and B cells (OR 0.72, 95% CI, 0.59-0.87), and a greater increase in cytotoxic T cells (OR 1.09, 95% CI, 1.03-1.16) were risk factors for poor overall survival. CONCLUSIONS: Circulating lymphocyte subsets of cancer patients presented characteristic changes after chemotherapy. Patients with a greater decrease in helper T cells and B cells, or greater increase in cytotoxic T cells, may have worse survival.

Genotyping and zoonotic potential of Enterocytozoon bieneusi in cattle farmed in Hainan Province, the southernmost region of China.

Enterocytozoon bieneusi is an intestinal pathogen that infects a wide range of species, including humans. Cattle constitute an important host for E. bieneusi; however, there is a scarcity of information on the prevalence and genotyping of E. bieneusi in cattle in the Hainan Province of China. In this study, PCR analysis of 314 fecal samples from cattle in six cities of Hainan was performed for genotype identification. The average prevalence of E. bieneusi in these animals was 9.9% (31/314), and ranged from 0.0% (0/12) to 20.5% (8/39). Five known genotypes - EbpC (n = 14), BEB4 (n = 12), J (n = 2), I (n = 1), and CHG5 (n = 1) - and a novel genotype: HNC-I (n = 1) - were identified. Genotypes EbpC and HNC-I were placed in zoonotic Group 1, and the remaining four genotypes (BEB4, J, I, and CHG5) were placed in Group 2. Since 93.5% of the genotypes found in the cattle (29/31) (EbpC, BEB4, J, and I) have previously been found in humans, these genotypes are probably involved in the transmission of microsporidiosis to humans.

TITLE: Génotypage et potentiel zoonotique d'Enterocytozoon bieneusi chez les bovins élevés dans la province de Hainan, la région la plus au sud de la Chine. ABSTRACT: Enterocytozoon bieneusi est un pathogène intestinal qui infecte un large éventail d'espèces, y compris les humains. Le bétail constitue un hôte important pour E. bieneusi, mais les informations sur la prévalence et le génotypage d'E. bieneusi chez les bovins de la province de Hainan en Chine sont rares. Dans cette étude, une analyse PCR de 314 échantillons fécaux provenant de bovins dans six villes de Hainan a été réalisée pour l'identification du génotype. La prévalence moyenne d'E. bieneusi chez ces animaux était de 9,9 % (31/314), et variait de 0,0 % (0/12) à 20,5 % (8/39). Cinq génotypes connus, EbpC (n = 14), BEB4 (n = 12), J (n = 2), I (n = 1) et CHG5 (n = 1), et un nouveau génotype, HNC-I (n = 1), ont été identifiés. Les génotypes EbpC et HNC-I sont placés dans le groupe zoonotique 1, et les quatre génotypes restants (BEB4, J, I et CHG5) sont placés dans le groupe 2. Puisque 93,5 % (29/31) (EbpC, BEB4, J et I) des génotypes trouvés chez les bovins ont déjà été trouvés chez l'homme, ces génotypes sont probablement impliqués dans la transmission de la microsporidiose à l'homme.

Comparison of severity index and plasma paraquat concentration for predicting survival after paraquat poisoning: A meta-analysis.

BACKGROUND: Severity index and plasma paraquat (PQ) concentration can predict the prognosis of patients with PQ poisoning. However, the better parameter is yet to be systematically investigated and determined. Thus, we conduct this systematic review and meta-analysis to investigate the prognostic value of severity index and plasma PQ concentration in patients with PQ poisoning. METHODS: We searched PubMed, Embase, Web of Science, ScienceDirect, and Cochrane Library to identify all relevant papers that were published up to March 2019. All diagnostic studies that compared severity index and plasma PQ concentration to predict mortality in patients with PQ poisoning were enrolled in this meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) for individual trials were pooled using a random-effect model. We also aggregated heterogeneity testing, sensitivity analysis, and publication bias analysis. RESULTS: Ultimately, seven studies involving 821 patients were included. The pooled OR with a 95% CI of severity index was 24.12 (95% CI: 9.34-62.34, P < .001), with an area under the curve of 0.88 (95% CI: 0.85-0.90), sensitivity of 0.84 (95% CI: 0.74-0.91), and specificity of 0.81 (95% CI: 0.75-0.87). Meanwhile, the pooled OR with 95% CI of plasma PQ concentration was 34.39 (95% CI: 14.69-80.56, P < .001), with an area under the curve of 0.94 (95% CI: 0.91-0.96), sensitivity of 0.86 (95% CI: 0.75-0.93), and specificity of 0.89 (95% CI: 0.76-0.95). Sensitivity analysis demonstrated the stability of the results of our meta-analysis. No significant publication bias was observed in this meta-analysis. CONCLUSION: Overall, this study indicated that severity index and plasma PQ concentration have relatively high-prognostic value in patients with PQ poisoning, and that the sensitivity and specificity of plasma PQ concentration are superior to those of severity index.

Prevention and Control of Pathogens Based on Big-Data Mining and Visualization Analysis.

Morbidity and mortality caused by infectious diseases rank first among all human illnesses. Many pathogenic mechanisms remain unclear, while misuse of antibiotics has led to the emergence of drug-resistant strains. Infectious diseases spread rapidly and pathogens mutate quickly, posing new threats to human health. However, with the increasing use of high-throughput screening of pathogen genomes, research based on big data mining and visualization analysis has gradually become a hot topic for studies of infectious disease prevention and control. In this paper, the framework was performed on four infectious pathogens (Fusobacterium, Streptococcus, Neisseria, and Streptococcus salivarius) through five functions: 1) genome annotation, 2) phylogeny analysis based on core genome, 3) analysis of structure differences between genomes, 4) prediction of virulence genes/factors with their pathogenic mechanisms, and 5) prediction of resistance genes/factors with their signaling pathways. The experiments were carried out from three angles: phylogeny (macro perspective), structure differences of genomes (micro perspective), and virulence and drug-resistance characteristics (prediction perspective). Therefore, the framework can not only provide evidence to support the rapid identification of new or unknown pathogens and thus plays a role in the prevention and control of infectious diseases, but also help to recommend the most appropriate strains for clinical and scientific research. This paper presented a new genome information visualization analysis process framework based on big data mining technology with the accommodation of the depth and breadth of pathogens in molecular level research.

Bone Turnover Markers and Bone Mineral Density to Predict Osteoporotic Fractures in Older Women: A Retrospective Comparative Study.

OBJECTIVE: To investigate the clinical significance of the detection of bone mineral density (BMD) and bone turnover markers (BTM) in older women with osteoporosis, and to compare their predictive power for osteoporotic fractures (OF). METHODS: In this retrospective study, 96 patients with OF and 107 patients with osteoporosis who were hospitalized in the Department of Orthopedics at the First Affiliated Hospital of Chengdu Medical College were examined from October 2017 to February 2019. All selected patients were divided into either the fracture group (96 cases, 47.3%) or the non-fracture group (107 cases, 52.7%). BMD was measured by dual-energy X-ray absorptiometry (DXA). BTM were detected by electrochemical luminescence: aminoterminal propeptide of type I procollagen (PINP), ß-cross-linked C-telopeptide of type I collagen (ß-CTX), and molecular fragment of osteocalcin N terminal (N-MID). Bone metabolism-related indicators were detected, including alkaline phosphatase (ALP), calcium (Ca), and phosphorus (P). Independent-samples t-tests were used to compare the measurement data between the two groups, one-way ANOVA to compare the gaps between groups, and binary logistic regression to analyze the correlation of BMD and BTM with OF. RESULTS: There were no significant differences in age, weight, height, body mass index, age, and time of menopause between the two groups. There were a total of 71 cases (35.0%) in group A (60-70 years), 80 cases (39.4%) in group B (71-80 years), and 52 cases (25.6%) in group C (81-90 years). The fracture group was compared with the non-fracture group for BMD in the lumbar (0.75 ± 0.05 vs 0.88 ± 0.13, 0.75 ± 0.16 vs 0.87 ± 0.09, 0.74 ± 0.21 vs 0.87 ± 0.12 g/cm2 ; P < 0.05), BMD in the hip (0.62 ± 0.16 vs 0.74 ± 0.14, 0.61 ± 0.15 vs 0.73 ± 0.0, 0.58 ± 0.13 vs 0.73 ± 0.08 g/cm2 ; P < 0.05), PINP (83.7 ± 5.7 vs 74.8 ± 5.0, 80.7 ± 4.1 vs 72.1 ± 5.1, 81.2 ± 7.0 vs 68.7 ± 6.3 ng/mL, P < 0.05), and ß-CTX (829.7 ± 91.5 vs 798.8 ± 52.2, 848.1 ± 71.2 vs 812.4 ± 79.0, 867.3 ± 53.1 vs 849.1 ± 67.2 pg./mL, P < 0.05). N-MID (19.0 ± 6.7 vs 21.3 ± 9.7, 16.2 ± 7.0 vs 18.0 ± 5.3 ng/mL, P < 0.05) in the fracture cases was lower than in the non-fracture cases for groups B and C, and there was statistical significance. Among the fracture cases, PINP in group A was higher than in group B and C, and ß-CTX in group C was higher than in group A and B (P < 0.05). There was no significant difference in the ALP, P, and Ca between the two groups (P > 0.05). Binary logistic regression analysis showed that for BMD in the lumbar and hip, ß-CTX and OF were significantly correlated (respectively, odds ratio [OR] = -4.182, 95% confidence interval [CI] 1.672-3.448; OR = 6.929, 95% CI 2.586-12.106; OR = 7.572, 95% CI 1.441-3.059), and the differences were statistically significant. PINP and N-MID were correlated with OF (respectively, OR = 4.213, 95% CI 0.978-1.005; OR = 2.510, 95% CI 1.070-1.134, P > 0.05), the difference was not statistically significant. CONCLUSION: Osteoporotic older women, with lower bone density and higher ß-CTX, are more likely to incur OF. ß-CTX is better than BMD at predicting OF and can help in its management and in implementing interventions in high-risk populations.

Procalcitonin for predicting catheter-associated bloodstream infection: A meta-analysis.

OBJECTIVE: The predictive accuracies of procalcitonin (PCT) in the diagnosis of catheter-associated bloodstream infection (CABSI) vary widely. This meta-analysis aimed to explore the predictive value of PCT for CABSI. METHODS: We searched PubMed, EMBase, Web of Science, ScienceDirect, Cochrane Library, and studies published up to 10 March 2019. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to evaluate PCT predictive value using Stata 14.0 software. RESULTS: The meta-analysis was composed of 7 studies, consisting of 347 subjects. Pooled analysis demonstrated that a high PCT was significantly correlated with CABSI (pooled OR = 23.36, 95%CI 12.43-43.91, P < .001) and medium heterogenicity (I = 36.9%, P = .147). The pooled sensitivity and specificity were 85% (95%CI 0.76-0.91) and 89% (95%CI 0.68-0.97), respectively. Although Begg funnel plot (P = .007) indicated the presence of publication bias among the included studies, the stability of the pooled outcomes was verified by the trim-and-fill method. Furthermore, sensitivity analyses did not show important differences in effect estimation. CONCLUSION: PCT is an effective predictor of CABSI. However, high-quality randomized controlled trials are needed to determine whether PCT could predict CABSI.

Genotype identification and phylogenetic analysis of Enterocytozoon bieneusi in farmed black goats (Capra hircus) from China's Hainan Province.

Enterocytozoon bieneusi is an important pathogen commonly found in humans and animals. Farmed animals with close contact to humans are important hosts of E. bieneusi. The role of goats in the transmission of E. bieneusi, however, remains unclear. In this study, 341 fresh fecal samples of black goats were collected from five locations in Hainan Province, China. Enterocytozoon bieneusi was identified and genotyped by sequences of the internal transcribed spacer (ITS) region. Phylogenetic analysis was performed by constructing a neighbor-joining tree of the ITS gene sequences. The average prevalence of E. bieneusi in black goats was 24.0% (82/341) with rates ranging from 6.3% (4/63) to 37.2% (32/86) across the locations (χ2 = 17.252, p < 0.01). Eight genotypes of E. bieneusi were identified, including six known genotypes: CHG5 (n = 47); CHG3 (n = 23); CHG2 (n = 4); CM21 (n = 3); D (n = 2); and AHG1 (n = 1), and two novel genotypes termed HNG-I (n = 1) and HNG-II (n = 1). In the phylogenetic tree, genotype D was clustered into Group 1 and the other identified genotypes were included in Group 2. This represents the first report identifying E. bieneusi in black goats from Hainan Province, with a high prevalence and wide occurrence demonstrated. The two new genotypes identified provide additional insights into the genotypic variations in E. bieneusi. Due to the small percentage of zoonotic genotypes in these animals, there is minimal risk of zoonotic transmission of E. bieneusi.

TITLE: Identification du génotype et analyse phylogénétique d'Enterocytozoon bieneusi chez des chèvres noires (Capra hircus) de la province de Hainan, en Chine. ABSTRACT: Enterocytozoon bieneusi est un agent pathogène important que l'on trouve couramment chez l'homme et les animaux. Les animaux d'élevage, en contact étroit avec l'homme, sont des hôtes importants d'E. bieneusi. Le rôle des chèvres dans la transmission d'E. bieneusi reste toutefois incertain. Dans cette étude, 341 échantillons de fèces fraîches de chèvres noires ont été prélevés dans cinq sites de la province de Hainan, en Chine. Enterocytozoon bieneusi a été identifié et génotypé par des séquences de la région de l'espaceur interne transcrit (ITS). L'analyse phylogénétique a été réalisée en construisant un arbre de jonction voisine des séquences du gène ITS. La prévalence moyenne d'E. bieneusi chez les chèvres noires était de 24,0 % (82/341), avec des taux allant de 6,3 % (4/63) à 37,2 % (32/86) dans tous les sites (χ2 = 17,252, p < 0,01). Huit génotypes d'E. bieneusi ont été identifiés, dont six génotypes connus: CHG5 (n = 47) ; CHG3 (n = 23) ; CHG2 (n = 4) ; CM21 (n = 3) ; D (n = 2) ; AHG1 (n = 1) et deux nouveaux génotypes appelés HNG-I (n = 1) et HNG-II (n = 1). Dans l'arbre phylogénétique, le génotype D appartenait au groupe 1 et les autres génotypes identifiés étaient inclus dans le groupe 2. Il s'agit du premier rapport identifiant E. bieneusi chez des chèvres noires de la province de Hainan, avec une prévalence élevée et une occurrence étendue. Les deux nouveaux génotypes identifiés fournissent des informations supplémentaires sur les variations génotypiques chez E. bieneusi. En raison du faible pourcentage de génotypes zoonotiques chez ces animaux, le risque de transmission zoonotique d'E. bieneusi est minime.

Neutrophil-lymphocyte ratio as an early predictor for patients with acute paraquat poisoning: A retrospective analysis.

This retrospective study aimed to investigate whether the neutrophil-lymphocyte ratio (NLR) can be used as an early predictor of 90-day survival in patients with acute paraquat (PQ) poisoning.This study enrolled 105 patients with acute PQ poisoning admitted from May 2012 to May 2018. Kaplan-Meier curve, receiver operating characteristic curve, and Cox proportional hazards regression analyses were used to investigate the predictive value of NLR for 90-day survival of patients with acute PQ poisoning.The 90-day survival rate was 40.95% (43/105). Survivors had lower NLR (P <.001), which was an independent predictor of 90-day survival according to the Cox proportional hazard regression analyses. The area under the NLR curve was 0.842 (95% CI: 0.767-0.917, P <.001) in predicting 90-day survival.Our findings showed that low NLR was a valuable early predictor of 90-day survival in patients with acute PQ poisoning.

Proton pump inhibitor use increases hepatic encephalopathy risk: A systematic review and meta-analysis.

BACKGROUND: Several studies have been conducted to explore the association between the use of proton pump inhibitors (PPIs) and hepatic encephalopathy (HE) risk in patients with liver cirrhosis. However, their results are controversial. AIM: To perform a systematic review and meta-analysis to evaluate the HE risk among PPI users. METHODS: A systematic search on PubMed, Web of Science, EMBase, and ScienceDirect databases was conducted up to December 31, 2018 for eligible studies involving PPI use and HE risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed or random effects model. Publication bias was evaluated using Begg's test, Egger's test, and trim-and-fill method. RESULTS: Seven studies with 4574 patients were included in the present meta-analysis. The meta-analysis results indicated a significant association between the PPI use and HE risk (OR = 1.50; 95%CI: 1.25-1.75) with low heterogeneity (I 2 = 14.2%, P = 0.321). Although publication bias existed when Egger's tests were used (P = 0.005), the trim-and-fill method verified the stability of the pooled result. Sensitivity analyses suggested that the results of this meta-analysis were robust. CONCLUSION: The current evidence indicates that PPI use increases HE risk in patients with liver cirrhosis. Further studies with a large data set and well-designed models are needed to validate our findings.

Platelet-lymphocyte ratio is not a prognostic predictor for acute paraquat-intoxicated patients: A retrospective analysis.

This study aimed to investigate the prognostic predictive value of the platelet-lymphocyte ratio (PLR) in patients with acute paraquat (PQ) intoxication.A total of 107 patients with acute PQ intoxication via oral ingestion were admitted in Cangzhou Central Hospital from May 2012 to September 2018. Valuable detection indices were screened out by using Cox proportional hazard regression and receiver operating characteristic (ROC) curve analyses, and their diagnostic efficiency was evaluated by using Kaplan-Meier curve.The 90-day mortality was 58.9% (63/107). The Kaplan-Meier curve showed that PLR was not associated with 90-day survival (log-rank test; P = .661). In Cox proportional hazard regression analyses, PLR was not an independent risk factor. Meanwhile, the ROC curves showed that PLR had an AUC value of 0.569 (95% confidence interval: 0.459-0.679, P = .227) in predicting 90-day survival.PLR is not a prognostic predictor for patients with acute PQ intoxication.

Postmortem Brain, Cerebrospinal Fluid, and Blood Neurotrophic Factor Levels in Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Accumulating evidence suggest that aberrations of neurotrophic factors are involved in the etiology and pathogenesis of Alzheimer's disease (AD), but clinical data were inconsistent. Therefore, a meta-analysis on neurotrophic factor levels in AD is necessary. We performed a systematic review of blood, CSF, and post-mortem brain neurotrophic factor levels in patients with AD compared with controls and quantitatively summarized the clinical data in blood and CSF with a meta-analytical technique. A systematic search of PubMed and Web of Science identified 98 articles in this study (with samples more than 9000). Random effects meta-analysis demonstrated that peripheral blood BDNF levels were significantly decreased in AD patients compared with controls. However, blood NGF, IGF, and VEGF did not show significant differences between cases and controls. In CSF, random effects meta-analysis showed significantly deceased BDNF and increased NGF levels in patients with AD, whereas IGF and VEGF did not show significant differences between the AD group and control group. In addition, 23 post-mortem studies were included in the systematic review. Although data from post-mortem brains were not always consistent across studies, most studies suggested decreased BDNF and increased (pro)NGF levels in hippocampus and neocortex of patients with AD. These results provide strong clinical evidence that AD is accompanied by an aberrant neurotrophin profile, and future investigations into neurotrophins as biomarkers (especially CSF BDNF and NGF) and therapeutic targets for AD may be warranted.

Prevalence of celiac disease in patients with Down syndrome: a meta-analysis.

BACKGROUND: The association between Down syndrome and celiac disease has been reported by many studies. However, the prevalence of celiac disease (CD) in Down syndrome (DS) varies considerably across studies (from 0 % to 19 %). The aim of this study was to use meta-analysis to exam the prevalence of CD in patients with DS. METHODS: A systematic search of English articles from Pubmed, Web of Science and CNKI without year limitation. Data were extracted by two independent observers and pooled using a random effects model by the Comprehensive Meta-Analysis Version 2 software. RESULTS: A pooled analysis, based on 31 studies included 4383 individuals, revealed prevalence of biopsy-confirmed CD of 5.8 % (95 % CI = 4.7-7.2 %) in patients with DS. Sub-group analysis showed a slightly higher prevalence of CD in children with DS (6.6 %; 17 studies), than in age mixed samples with both children and adults (5.1 %; 13 studies). In addition, most of the studies included in this meta-analysis were from Europe and America, with the prevalence of celiac disease of 6 % (21 studies) and 5.7 % (6 studies) in DS patients, respectively. Furthermore, meta-regression analysis suggested that proportion of antibody-positive individuals that underwent small intestine biopsy had moderating effect on the outcome of the meta-analysis. CONCLUSIONS: These results demonstrated that patients (children) with Down syndrome had high prevalence of CD (more than one in twenty). The prevalence is high enough to motivate screening CD in DS children.

Spatial pattern and variations in the prevalence of congenital heart disease in children aged 4-18 years in the Qinghai-Tibetan Plateau.

PURPOSE: This study aimed to investigate the spatial distribution pattern of the prevalence of congenital heart disease (CHD) in children in Qinghai-Tibetan Plateau (QTP), a high-altitude region in China. METHODS: Epidemiological data from a survey on the prevalence of CHD in Qinghai Province including 288,066 children (4-18 years) were used in this study. The prevalence and distribution pattern of CHD was determined by sex, CHD subtype, and nationality and altitude. Spatial pattern analysis using Getis-Ord Gi⁎ was used to identify the spatial distribution of CHD. Bayesian spatial binomial regression was performed to examine the relationship between the prevalence of CHD and environmental risk factors in the QTP. RESULTS: The prevalence of CHD showed a significant spatial clustering pattern. The Tibetan autonomous prefecture of Yushu (average altitude > 4000 m) and the Mongolian autonomous county of Henan (average altitude > 3600 m) in Huangnan had the highest prevalence of CHD. Univariate analysis showed that with ascending altitude, the total prevalence of CHD, that in girls and boys with CHD, and that of the subtypes PDA and ASD increasing accordingly. Thus, environmental factors greatly contributed to the prevalence of CHD. CONCLUSIONS: The prevalence of CHD shows significant spatial clustering pattern in the QTP. The CHD subtype prevalence clustering pattern has statistical regularity which would provide convenient clues of environmental risk factors. Our results may provide support to make strategies of CHD prevention, to reduce the incidence of CHD in high altitude regions of China.

MiR-449 overexpression inhibits osteogenic differentiation of bone marrow mesenchymal stem cells via suppressing Sirt1/Fra-1 pathway in high glucose and free fatty acids microenvironment.

Diabetic osteoporosis is a chronic complication caused by diabetes mellitus, and However, the exact mechanism of diabetes mellitus-induced osteoporosis is still unknown. In this study, we investigate the effect of miR-449 on osteogenic differentiation and its underlying mechanism in human bone marrow-derived mesenchymal stem cells (hBMSCs) with high glucose (HG) and free fatty acids (FFA) treatment. Results showed that after culturing for 14 days, high glucose (HG) and free fatty acids (FFA) treatment dramatically decreased mineralization of human bone marrow-derived mesenchymal stem cells (hBMSCs) compared with cells treated with osteogenic medium (OM) alone. We also found that miR-449 expression was up-regulated during osteogenic differentiation of hBMSCs with HG and FFA treatment. Moreover, during osteogenic differentiation of hBMSCs with HG and FFA treatment, miR-449 mimics notably decreased the alkaline phosphatase (ALP) activity and the mRNA and protein expression levels of runt-related transcription factor 2 (Runx2), ALP, collagen I, osteocalcin (OCN), and bone sialoprotein (BSP), which was remarkably increased by miR-449 inhibitors. Furthermore, miR-449 directly targets Sirt1 by binding to its 3'-UTR. Sirt1 overexpression reverses the suppressive effect of miR-449 mimics on Fra-1 mRNA and protein expression, which was also alleviated by Fra-1 overexpression. In addition, Fra-1 overexpression alleviates the inhibitory effect of miR-449 mimics on the ALP activity and the mRNA and protein of Runx2, collagen I, OCN and BSP. Taken together, our results indicated that miR-449 overexpression inhibited osteogenic differentiation of HG-FFA-treated hBMSCs through the Sirt1/Fra-1 signal pathway. It is conceivable that modulating miR-449 might provide a new therapy for intervention in diabetic osteoporosis.