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Background: This study aimed to test the reliability and validity of the Hip Inflammation MRI Scoring System (HIMRISS) in assessing hip involvement of AS patients with AS at different stages of the bath ankylosing spondylitis radiology index (BASRI-hip) scoring system.Methods: Fifty-two outpatients with ankylosing spondylitis (AS) were included in this study. The subjects' data includes demographics, clinical characteristics, disease activity score, and functional index. Based on the Harris hip scoring (HHS) of involved hip and BASRI-hip score, we devided these patients into no hip involvement group((HHS ≥ 80 and BASRI ≤ 1) (Group A), mild hip involvement subgroup (BASRI = 2 or BASRI ≤ 1 and HHS ≤ 79) (Group B), and moderate to advanced hip involvement subgroup (BASRI ≥ 3) (Group C). Data was analyzed statistically by SPSS software.Results: In total of 44 patients (88 hips), group A consisted of 21 hips, group B consisted of 42 hips and group C consisted of 25 hips. The test-retest intraclass correlation coefficients (ICCs) in four raters were 0.955 ~ 0.977 and interrater ICC was 0.993. HIMRISS correlated moderately with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (r = 0.540, p < 0.001), the Bath ankylosing spondylitis functional index (BASFI) (r = 0.540, p < 0.001), the Bath Ankylosing Spondylitis Functional Index (BASFI) (r = 0.581, p < 0.001), ASDAS-ESR (r = 0.604, p < 0.001), and Ankylosing Spondylitis Disease Activity Score (ASDAS)-C reactive protein (CRP) (r = 0.575, p < 0.001). HIMRISS in groups B and C was significantly higher than that in group A: 29.38 (17.00, 40.94) vs. 14.50 (11.38, 22.25), p = 0.009; 38 (31.13, 64.38) vs 14.50 (11.38, 22.25), p < 0.001.Conclusions: HIMRISS applied to patients with AS demonstrated a satisfactory reliability, meaning it is a reliable quantitive assessment tool for evaluating early hip involvement in patients with AS. [ABSTRACT FROM AUTHOR]

Background: Obesity and other metabolic diseases have become epidemic which greatly affect human health. Diets with healthy nutrition are efficient means to prevent this epidemic occurrence. Novel food resources and process technology were needed for these purpose. In this study, Antarctic krill oil (KO) extracted from a dry krill by a procedure of hot pump dehydration in combined with freezing-drying was used to investigate health effect in animals including the growth, lipid and glucose metabolism. Methods: C57BL/6J mice were fed with a lard based high fat (HF) diet and substituted with KO for a period of 12 weeks in comparison with low fat normal control (NC) diet. Mice body weight and food consumption were recorded. Serum lipid metabolism - of C57BL/6J mice serum was measured. A glucose tolerance tests (GTTs) and pathology analysis of mice were performed at the end of the experiment. Results: The KO fed mice had less body weight gain, less fat accumulation in tissue such as adipose and liver. Dyslipidemia induced by high fat diet was partially improved by KO feeding with significant reduction of serum low density lipoprotein-cholesterol (LDL-C) content. Furthermore, KO feeding also improved glucose metabolism in C57BL/6J mice including a glucose tolerance of about 22% vs. 32% of AUC (area under the curve) for KO vs HF diet and the fast blood glucose level of 8.5 mmol/L, 9.8 mmol/L and 9.3 mmol/L for NC, HF and KO diet groups, respectively. In addition, KO feeding also reduced oxidative damage in liver with a decrease of malondialdehyde (MDA) content and increase of superoxide dismutase (SOD) content. Conclusion: This study provided evidence of the beneficial effects of KO on animal health from the processed technology, particularly on lipid and glucose metabolism. This study confirmed that as the Antarctic krill was extracted with a procedure of efficient energy, it might make it possible for Krill oil to be available for food industry. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is an important independent modifiable risk factor for cardiovascular disease. The aim of this study was to explore the current prevalence, awareness, treatment and control of dyslipidemia and its associated influence factors in northeast China. Methods: In this population-based cross-sectional study, we adopted a multi-stage, stratified sampling method to obtain a representative sample of 4052 permanent residents aged 40 years and over from different urban and rural regions in Dehui City of Jilin Province. All subjects completed a questionnaire and were examined for risk factors. Continuous data were presented as means ± standard deviations (SD) and compared using the Student’s t-test. Categorical variables were presented as proportions and compared using the Rao-Scott-χ2 test in different subgroups. The associated influence factors for the prevalence, awareness, treatment and control of dyslipidemia were evaluated through multivariate logistic regression. Results: The prevalence of dyslipidemia was 62.1% overall, with 33.5, 43.9, 0.6, and 8.8% for high total cholesterol, triglyceride, low-density lipoprotein cholesterol, and low high-density lipoprotein cholesterol, respectively. Among those with dyslipidemia, the proportion of subjects who were aware, treated, and controlled was 14.4, 33.9, and 19.9%, respectively. Overweight or obesity (OR = 2.156; 95% CI: 1.863, 2.533), hypertension (OR = 1.643; 95% CI: 1.425, 1.893), or diabetes mellitus (OR = 2.173; 95% CI: 1.661, 2.844) increased the prevalence of dyslipidemia, also these participants were more likely to be aware of their condition, however, this did not increase the likelihood of treatment and control. Living in urban areas and higher education level also increased the awareness of dyslipidemia. Personal history of coronary heart disease was the strongest influence factors associated with better awareness, treatment and control of dyslipidemia. Overweight or obesity (OR = 0.404; 95% CI: 0.235, 0.695) and lack of exercise (OR = 0.423; 95% CI: 0.215, 0. 830) were associated with poor control of dyslipidemia. Conclusion: The prevalence of dyslipidemia among adults aged 40 years and over in northeast China was high, however, the awareness, treatment, and control of dyslipidemia was measured at far from desirable levels. Renewed efforts taking influence factors into account are needed to improve the current unsatisfactory condition. [ABSTRACT FROM AUTHOR]

Background: To compare the efficacy of sorafenib and sunitinib with regard to overall survival (OS) and progression free survival (PFS) in Chinese patients with metastatic renal cell carcinoma (mRCC).Methods: A multicenter, retrospective study was performed to elucidate the relationship between clinical variables and prognosis comparing sorafenib and sunitinib as first-line treatment agents in Chinese patients with mRCC. Between September 2006 and December 2014, 845 patients received either sorafenib (400 mg bid; n = 483) or sunitinib (50 mg q.d; n = 362). The primary end point was OS and PFS.Results: The percentage of patients with low and moderate risk according to Memorial Sloan-Kettering Cancer Centre (MSKCC) score was significantly higher in sunitinib group, and that with high risk was significantly higher in sorafenib group (15.1 vs. 5.2%; p < 0.001). Median OS was similar in sorafenib and sunitinib group (24 vs. 24 months; p = 0.298). Sorafenib group exhibited higher mPFS compared to sunitinib group (11.1 vs. 10.0 months; p = 0.028). Treatment (sorafenib vs sunitinib), pathology, Eastern Cooperative Oncology Group (ECOG) performance status, MSKCC scores, Heng's criteria of risk, and number of metastases were identified as significant predictors for OS and along with liver metastasis for PFS. Clinical outcomes in terms of mOS was significantly better with sorafenib in patients ≥65 years of age (p = .041), ECOG 0 (p = 0.0001), and median MSKCC risk score (p = 0.008).Conclusions: Sorafenib and sunitinib are both effective in treating mRCC. However, sorafenib might be more effective in elderly patients (≥65 years) and in patients with an ECOG status of 0, classified under MSKCC moderate risk. [ABSTRACT FROM AUTHOR]

Background: Integrative strategy of health services delivery has been proven to be effective in economically developed countries, where the healthcare systems have enough qualified primary care providers. However rural China lacks such providers to act as gatekeeper, besides, Chinese rural hypertensive patients are usually of old age, more likely to be exposed to health risk factors and they experience a greater socio-economic burden. All these Chinese rural setting specific features make the effectiveness of integrative strategy of health services in improving health related quality of life among Chinese rural hypertensive patients uncertain. Methods: In order to assess the impact of integrative strategy of health services delivery on health related quality of life among Chinese rural hypertensive patients, a two-year quasi-experimental trial was conducted in Chongqing, China. At baseline the sample enrolled 1006 hypertensive patients into intervention group and 420 hypertensive patients into control group. Physicians from village clinics, town hospitals and county hospitals worked collaboratively to deliver multidisciplinary health services for the intervention group, while physicians in the control group provided services without cooperation. The quality of life was studied by SF-36 Scale. Blood pressures were reported by town hospitals. The Difference-in-Differences model was used to estimate the differences in SF-36 score and blood pressure of both groups to assess the impact. Results: The study showed that at baseline there was no statistical difference in SF-36 scores between both groups. While at follow-up the intervention group scored higher in overall SF-36, Role Physical, Body Pain, Social Functioning and Role Emotional than the control group. The Difference-in-Differences result demonstrated that there were statistical differences in SF-36 total score (p = 0.011), Role Physical (p = 0.027), Social Functioning (p = 0.000), Role Emotional (p = 0.002) between both groups. Integrative services delivery improved the score of SF-36 by 4.591 ± 1.794, and also improved the score in domains of Role Physical, Social Functioning and Role Emotional by 8.289 ± 3.753, 9. 762 ± 2.019 and 12.534 ± 4.083, respectively. Conclusion: Patients in the intervention group obtained lower systolic blood pressure and diastolic blood pressure. Integrative strategy of health services delivery improved health related quality of life and blood pressure control among rural Chinese hypertensive patients. [ABSTRACT FROM AUTHOR]

Background: Previous studies confirmed that ground-glass nodules (GGNs) with certain CT manifestations had a higher probability of malignancy. However, differentiating patchy ground-glass opacities (GGOs) and GGNs has not been discussed solely. This study aimed to investigate the differences between the CT features of benign and malignant patchy GGOs to improve the differential diagnosis.Methods: From January 2016 to September 2021, 226 patients with 247 patchy GGOs (103 benign and 144 malignant) confirmed by postoperative pathological examination or follow-up were retrospectively enrolled. Their clinical and CT data were reviewed, and their CT features were compared. A binary logistic regression analysis was performed to reveal the predictors of malignancy.Results: Compared to patients with benign patchy GGOs, malignant cases were older (P <  0.001), had a lower incidence of malignant tumor history (P = 0.003), and more commonly occurred in females (P = 0.012). Based on CT images, there were significant differences in the location, distribution, density pattern, internal bronchial changes, and boundary between malignant and benign GGOs (P <  0.05). The binary logistic regression analysis revealed that the independent predictors of malignant GGOs were the following: patient age ≥ 58 years [odds ratio (OR), 2.175; 95% confidence interval (CI), 1.135-6.496; P = 0.025], locating in the upper lobe (OR, 5.481; 95%CI, 2.027-14.818; P = 0.001), distributing along the bronchovascular bundles (OR, 12.770; 95%CI, 4.062-40.145; P < 0.001), centrally distributed solid component (OR, 3.024; 95%CI, 1.124-8.133; P = 0.028), and well-defined boundary (OR, 5.094; 95%CI, 2.079-12.482; P < 0.001).Conclusions: In older patients (≥58 years), well-defined patchy GGOs with centric solid component, locating in the upper lobe, and distributing along the bronchovascular bundles should be highly suspected as malignancy. [ABSTRACT FROM AUTHOR]

Background: Self-rated health among old adults (SHOA) indicates individuals' subjective assessments and evaluations of their overall health based on objective physical circumstances. The purpose of this study was to analyze the current state and influencing factors of the subjective perception-based self-rated health (SH) by qualifying selected older adults with similar objective physical conditions, as well as to explore the equality and changing trends of SHOA based on influencing factors. Methods: This study designed a cross-sectional study, conducted in three provinces in east, central and west China, and included 1,153 older adults (> = 60 years) with intact physical condition (IPC). The current state of SHOA and its influencing factors were analyzed using mean comparisons and Logistic regression (LR) models. The equality level and trend of SHOA's effect on health literacy, health habits, and access to health care were determined using the Lorenz curve, Gini coefficient, and Vector Autoregression (VAR) model. Results: The mean SHOA with IPC was 74.37 ± 13.22. Findings from LR modeling indicated that SHOA with IPC was mainly influenced by age and communication methods (P < 0.05). It was also observed that the total Gini coefficient of the allocation of SHOA with IPC based on communication methods was equal to 0.0188, and the VAR results showed that the total effect of change in SHOA on health literacy among older adults was negative and its duration of the effect exceeded 50. Conclusions: The SHOA with IPC was shown to be better and was primarily influenced by age and communication methods. The observed effect of SHOA on health literacy was negative and lasting. To improve SHOA with IPC even further, policymakers could consider promoting the use of modern and convenient communication methods (such as smartphones) through training and purchasing subsidies, as well as focusing on increasing sustained attention and promoting health literacy and behavior among older adults with improved SH. [ABSTRACT FROM AUTHOR]

Background: Percutaneous vertebroplasty (PVP) typically involves conventional lower-viscosity cement injection via bipedicular approach. Limited evidence is available comparing the clinical outcomes and complications in treating osteoporotic vertebral compression fractures (OVCFs) with PVP using high-viscosity cement through unipedicular or bipedicular approach. Methods and design: Fifty patients with OVCFs were randomly allocated into two groups adopting unipedicular or bipedicular PVP. The efficacy of unipedicular and bipedicular PVP was assessed by comparing operation time, X-ray exposure time, incidence of complications, vertebral height restoration, and improvement of the visual analogue scale (VAS), Oswestry disability index (ODI) and Short Form-36 (SF-36) General Health Survey scores. Results: The mean operative and exposure time to X-rays in the unipedicular PVP group was less than that of the bipedicular group (p < 0.05). No statistically significant differences were observed in the VAS score, ODI score, SF-36 score, cement leakage rate or vertebral height restoration between the two groups (p > 0.05). Conclusion: Unipedicular and bipedicular PVP are safe and effective treatments for OVCF. Compared with bipedicular PVP, unipedicular PVP entails a shorter surgical time and lower X-ray irradiation. [ABSTRACT FROM AUTHOR]

Background: Percutaneous vertebroplasty (PVP) typically involves conventional lower-viscosity cement injection via bipedicular approach. Limited evidence is available comparing the clinical outcomes and complications in treating osteoporotic vertebral compression fractures (OVCFs) with PVP using high-viscosity cement through unipedicular or bipedicular approach. Methods and design: Fifty patients with OVCFs were randomly allocated into two groups adopting unipedicular or bipedicular PVP. The efficacy of unipedicular and bipedicular PVP was assessed by comparing operation time, X-ray exposure time, incidence of complications, vertebral height restoration, and improvement of the visual analogue scale (VAS), Oswestry disability index (ODI) and Short Form-36 (SF-36) General Health Survey scores. Results: The mean operative and exposure time to X-rays in the unipedicular PVP group was less than that of the bipedicular group (p < 0.05). No statistically significant differences were observed in the VAS score, ODI score, SF-36 score, cement leakage rate or vertebral height restoration between the two groups (p > 0.05). Conclusion: Unipedicular and bipedicular PVP are safe and effective treatments for OVCF. Compared with bipedicular PVP, unipedicular PVP entails a shorter surgical time and lower X-ray irradiation. [ABSTRACT FROM AUTHOR]

Background: Jasmonic acid (JA) and methyl jasmonate (MeJA) regulate plant development, resistance to stress, and insect attack by inducing specific gene expression. However, little is known about the mechanism of plant defense against herbivore attack at a protein level. Using a high-resolution 2-D gel, we identified 62 MeJA-responsive proteins and measured protein expression level changes. Results: Among these 62 proteins, 43 proteins levels were increased while 11 proteins were decreased. We also found eight proteins uniquely expressed in response to MeJA treatment. Data are available via ProteomeXchange with identifier PXD001793. The proteins identified in this study have important biological functions including photosynthesis and energy related proteins (38.4%), protein folding, degradation and regulated proteins (15.0%), stress and defense regulated proteins (11.7%), and redox-responsive proteins (8.3%). The expression levels of four important genes were determined by qRT-PCR analysis. The expression levels of these proteins did not correlate well with their translation levels. To test the defense functions of the differentially expressed proteins, expression vectors of four protein coding genes were constructed to express in-fusion proteins in E. coli. The expressed proteins were used to feed Ostrinia furnacalis, the Asian corn borer (ACB). Our results demonstrated that the recombinant proteins of pathogenesis-related protein 1 (PR1) and thioredoxin M-type, chloroplastic precursor (TRXM) showed the significant inhibition on the development of larvae and pupae. Conclusions: We found MeJA could not only induce plant defense mechanisms to insects, it also enhanced toxic protein production that potentially can be used for bio-control of ACB. [ABSTRACT FROM AUTHOR]

Background Epidermal growth factor receptor (EGFR) is amplified in 40% of human glioblastomas. However, most glioblastoma patients respond poorly to anti-EGFR therapy. MicroRNAs can function as either oncogenes or tumor suppressor genes, and have been shown to play an important role in cancer cell proliferation, invasion and apoptosis. Whether microRNAs can impact the therapeutic effects of EGFR inhibitors in glioblastoma is unknown. Methods miR-566 expression levels were detected in glioma cell lines, using real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate VHL as a direct target gene of miR-566. Cell proliferation, invasion, cell cycle distribution and apoptosis were also examined to confirm whether miR-566 inhibition could sensitize anti-EGFR therapy. Results In this study, we demonstrated that miR-566 is up-regulated in human glioma cell lines and inhibition of miR-566 decreased the activity of the EGFR pathway. Lentiviral mediated inhibition of miR-566 in glioblastoma cell lines significantly inhibited cell proliferation and invasion and led to cell cycle arrest in the G0/G1 phase. In addition, we identified von Hippel-Lindau (VHL) as a novel functional target of miR-566. VHL regulates the formation of the ß-catenin/hypoxia-inducible factors-1a complex under miR-566 regulation. Conclusions miR-566 activated EGFR signaling and its inhibition sensitized glioblastoma cells to anti-EGFR therapy. [ABSTRACT FROM AUTHOR]

Background Rats exhibit extremely limited motor function recovery after total transection of the spinal cord (SCT). We previously reported that SM-216289, a semaphorin3A inhibitor, enhanced axon regeneration and motor function recovery in SCT adult rats. However, these effects were limited because most regenerated axons likely do not connect to the right targets. Thus, rebuilding the appropriate connections for regenerated axons may enhance recovery. In this study, we combined semaphorin3A inhibitor treatment with extensive treadmill training to determine whether combined treatment would further enhance the "rewiring" of regenerated axons. In this study, which aimed for clinical applicability, we administered a newly developed, potent semaphorin3A inhibitor, SM-345431 (Vinaxanthone), using a novel drug delivery system that enables continuous drug delivery over the period of the experiment. Results Treatment with SM-345431 using this delivery system enhanced axon regeneration and produced significant, but limited, hindlimb motor function recovery. Although extensive treadmill training combined with SM-345431 administration did not further improve axon regeneration, hindlimb motor performance was restored, as evidenced by the significant improvement in the execution of plantar steps on a treadmill. In contrast, control SCT rats could not execute plantar steps at any point during the experimental period. Further analyses suggested that this strategy reinforced the wiring of central pattern generators in lumbar spinal circuits, which, in turn, led to enhanced motor function recovery (especially in extensor muscles). Conclusions This study highlights the importance of combining treatments that promote axon regeneration with specific and appropriate rehabilitations that promote rewiring for the treatment of spinal cord injury. [ABSTRACT FROM AUTHOR]

Background Quickly and accurately localizing small peripheral pulmonary lesions can avoid prolonged operative time and unplanned open thoracotomy. In this study, we aimed to introduce and evaluate a new technique combining virtual simulation and methylene blue staining for the localization of small peripheral pulmonary lesions. Methods Seventy four (74) patients with 80 peripheral pulmonary lesions<20 mm in size on computer tomography (CT) were virtually punctured using a radiotherapy planning simulator on the day before operation. Under general anaesthesia, methylene blue dye was injected to the virtually identified point according to the surface point, angle and depth previously determined by the simulator. The wedge resection of the marked lesion was performed under video-assisted thoracoscopic surgery (VATS) and the specimens were sent for immediate pathologic examination. According to pathology results, appropriate surgical procedures were decided and undertaken. Results The average lesion size was 10.4±3.5 mm (range: 4-17 mm) and the average distance to the pleural surface was 9.4±4.9 mm. Our preoperative localization procedure was successful in 75 of 80 (94%) lesions. Histological examination showed 28 benign lesions and 52 lung cancers. The shortest distance between the edges of the stain and lesion was 5.1±3.1 mm. Localization time was 17.4±2.3 min. All patients with malignant lesions subsequently underwent lobectomy and systematic lymph node dissection. No complications were observed in all participants. Conclusions The novel technique combining the preoperative virtual simulation and methylene blue staining techniques has a high success rate for localizing small peripheral pulmonary lesions, particularly for those tiny lesions which are difficult to visualise and palpate during VATS. [ABSTRACT FROM AUTHOR]

Background Melphalan resistance has been considered one of the major obstacles to improve outcomes in multiple myeloma (MM) therapy; unfortunately, the mechanistic details of this resistance remain unclear. Melphalan is a highly effective alkylating agent which causes many types of DNA lesions, including DNA base alkylation damage that is repaired by base excision repair (BER). We postulated that human apurinic/apyrimidinic endonuclease 1 (APE1), an essential BER enzyme, plays a vital role in acquired melphalan resistance. However, because APE1 is a multifunctional protein with redox activity and acetylation modification in addition to its major repair activity, the particular APE1 function that may play a more important role in melphalan resistance is unknown. Methods Two MM cell lines, RPMI-8226 and U266 were used to measure the difference in APE1 levels in melphalan-resistant and sensitive derivatives. APE1 functional mutants for DNA repair, redox and acetylation were employed to investigate the roles of individual APE1 activities in acquired melphalan resistance. Results Our results indicate that APE1 is overexpressed in both MM melphalan-resistant cells. Knocking down APE1 sensitizes the melphalan resistant MM cells to melphalan treatment. The exogenous expression of DNA repair mutant H309N and acetylation mutant K6R/K7R of APE1 failed to restore the melphalan resistance of the APE1 knockdown RPMI-8226 cells. The AP endonuclease activity and multidrug resistance protein 1 (MDR1) regulatory activity may play roles in the melphalan resistance of MM cells. Conclusions The present study has identified that the DNA repair functions and the acetylation modification of APE1 are involved in melphalan resistance of MM cells and has also shed light on future therapeutic strategies targeting specific APE1 functions by small molecule inhibitors. [ABSTRACT FROM AUTHOR]

Background Locoweeds cause significant livestock poisoning and economic loss all over the world. Animals can develop locoism, a chronic neurological disease, after grazing on locoweeds. Oxytropis kansuensis is a variety of locoweed that contains swainsonine as its main toxic ingredient. The purpose of this study was to investigate the apoptotic pathway induced in the cerebrum by swainsonine. Results Twenty-four Sprague-Dawley rats were randomly divided into four groups (experimental groups I, II, III and a control group) and 6 SD rats of each group were feed in 3 cages separately. Rats were penned as groups and fed with feeds containing 15% (SW content 0.03‰), 30% (SW content 0.06‰), or 45% (SW content 0.09‰) O. kansuensis for experimental groups I, II, and III, respectively, or complete feed in the case of the control group. One hundred and nineteen days after poisoning, and all rats showed neurological disorders at different degrees, which were considered to be successful established a chronic poisoning model of O. kansuensis. rats were sacrificed and the expression of Fas, FasL, Bcl- 2, Bax as well as cleaved caspase-3, -8 and -9 proteins in brain tissues were detected by Western blot. The results showed that SW treatment up-regulated Fas and Fas ligand (FasL) (P < 0.05), and that there was an increase in Bax and a decrease in Bcl-2 protein (P < 0.01). Moreover, SW treatment significantly increases the activation of caspase-3, 8 and -9, the key effectors in apoptosis pathway (P < 0.01).Conclusion Our data suggest that SW induces apoptosis in cells of the brain through death receptor and mitochondria-mediated, caspase-dependent apoptotic pathways in the brain tissue of SD rats. [ABSTRACT FROM AUTHOR]

Background: With an increasing incidence of congenital heart defects (CHDs) in recent years, genotype-phenotype correlation and array-based methods have contributed to the genome-wide analysis and understanding of genetic variations in the CHD population. Here, we report a copy number deletion of chromosomal 14q23.1 in a female fetus with complex congenital heart defects. This is the first description of DAAM1 gene deletion associated with congenital heart anomalies.Case Presentation: Compared with the control population, one CHD fetus showed a unique copy number delation of 14q23.1, a region that harbored DAAM1 and KIAA0666 genes.Conclusions: Results suggest that the copy number deletion on chromosome 14q23.1 may be critical for cardiogenesis. However, the exact relationship and mechanism of how DAAM1 and KIAA0666 deletion contributes to the onset of CHD is yet to be determined. [ABSTRACT FROM AUTHOR]

Background: The fern genus Dryopteris (Dryopteridaceae) is among the most common and species rich fern genera in temperate forests in the northern hemisphere containing 225-300 species worldwide. The circumscription of Dryopteris has been controversial and various related genera have, over the time, been included in and excluded from Dryopteris. The infrageneric phylogeny has largely remained unclear, and the placement of the majority of the supraspecific taxa of Dryopteris has never been tested using molecular data. Results: In this study, DNA sequences of four plastid loci (rbcL gene, rps4-trnS spacer, trnL intron, trnL-F spacer) were used to reconstruct the phylogeny of Dryopteris. A total of 122 accessions are sampled in our analysis and they represent 100 species of the expanded Dryopteris including Acrophorus, Acrorumohra, Diacalpe, Dryopsis, Nothoperanema, and Peranema. All four subgenera and 19 sections currently recognized in Dryopteris s.s. are included. One species each of Arachniodes, Leptorumohra, and Lithostegia of Dryopteridaceae are used as outgroups. Our study confirms the paraphyly of Dryopteris and provides the first strong molecular evidence on the monophyly of Acrophorus, Diacalpe, Dryopsis, Nothoperanema, and Peranema. However, all these monophyletic groups together with the paraphyletic Acrorumohra are suggested to be merged into Dryopteris based on both molecular and morphological evidence. Our analysis identified 13 well-supported monophyletic groups. Each of the 13 clades is additionally supported by morphological synapomophies and is inferred to represent a major evolutionary lineagein Dryopteris. In contrast, monophyly of the four subgenera and 15 out of 19 sections currently recognized in Dryopteris s.s is not supported by plastid data. Conclusions: The genera, Acrophorus, Acrorumohra, Diacalpe, Dryopsis, Nothoperanema, and Peranema, should all be merged into Dryopteris. Most species of these genera share a short rhizome and catadromic arrangement of frond segments, unlike the sister genus of Dryopteris s.l., Arachniodes, which has anadromic arrangement of frond segments. The non-monophyly of the 19 out of the 21 supraspecific taxa (sections, subgenera) in Dryopteris strongly suggests that the current taxonomy of this genus is in need of revision. The disagreement between the previous taxonomy and molecular results in Dryopteris may be due partly to interspecific hybridization and polyplodization. More morphological studies and molecular data, especially from the nuclear genome, are needed to thoroughly elucidate the evolutionary history of Dryopteris. The 13 well-supported clades identified based on our data represent 13 major evolutionary lineages in Dryopteris that are also supported by morphological synapomophies. [ABSTRACT FROM AUTHOR]

Background: Evidence indicates that CYP1A1 MspI polymorphism might be a possible risk factor for several malignancies. A growing body of literature has been devoted to the association of CYP1A1 MspI polymorphism with acute myeloid leukemia (AML). However, the results remain conflicting. The aim of the present study was to derive a more precise estimation of the relationship. Methods: Meta-analyses assessing the association of CYP1A1 MspI variation with AML were conducted and subgroup analyses on ethnicity and age groups were further performed. Eligible studies were identified for the period up to May 2012. Results: A total of ten case-control studies including 1330 cases and 3688 controls were selected for analysis. The overall data failed to indicate a significant association of CYP1A1 MspI polymorphism with AML risk (C vs T: OR = 1.13; 95%CI = 0.87-1.48; CC vs TT: OR = 1.72; 95%CI = 0.99-3.01; CC + TC vs TT: OR = 1.16; 95%CI = 0.86-1.55). In subgroup analysis stratified by ethnicity, significant AML risk was shown among Asians (CC + TC vs TT: OR = 1.33; 95%CI = 1.09-1.62) but not Caucasians or mixed races. In subgroup analysis regarding age groups, no associations were observed in either the childhood AML or the adult AML subgroups. Conclusion: The results of the present study suggested that CYP1A1 MspI polymorphism might be a risk factor for AML among Asians. Further investigations are needed to confirm the conclusions. [ABSTRACT FROM AUTHOR]

Foot-and-Mouth Disease (FMD), as a major global animal disease, affects millions of animals worldwide and remains the main sanitary barrier to the international and national trade of animals and animal products. Inactivated vaccination is the most effective measure for prevention of FMD at present, but fail to induce long-term protection and content new requires for production of FMD vaccines. As a number of Researchers hope to obtain satisfactory novel vaccines by new bio-technology, novel vaccines have been studied for more than thirty years. Here reviews the latest research progress of new vaccines, summarizes some importance and raises several suggestions for the future of FMD vaccine. [ABSTRACT FROM AUTHOR]

Background: Mitogen-activated protein kinase (MAPK) cascades play pivotal roles in mediating biotic and abiotic stress responses. In plants, MAPKs are classified into four major groups (A-D) according to their sequence homology and conserved phosphorylation motifs. Members of group A and B have been extensively characterized, but little information on the group D MAPKs has been reported. Results: In this study, we isolated and characterised GhMPK16, the first group D MAPK gene found in cotton. Southern blot analysis suggests GhMPK16 is single copy in the cotton genome, and RNA blot analysis indicates that GhMPK16 transcripts accumulate following pathogen infection and treatment with multiple defense-related signal molecules. The analysis of the promoter region of GhMPK16 revealed a group of putative cis-acting elements related to stress responses. Subcellular localization analysis suggests that GhMPK16 acts in the nucleus. Transgenic Arabidopsis overexpressing GhMPK16 displayed significant resistance to fungi (Colletotrichum nicotianae and Alternaria alternata) and bacteria (Pseudomonas solanacearum) pathogen, and the transcripts of pathogen-related (PR) genes were more rapidly and strongly induced in the transgenic plants. Furthermore, transgenic Arabidopsis showed reduced drought tolerance and rapid H2O2 accumulation. Conclusion: These results suggest that GhMPK16 might be involved in multiple signal transduction pathways, including biotic and abiotic stress signaling pathways. [ABSTRACT FROM AUTHOR]

Background: Insect cuticle plays essential roles in many physiological functions. During molting and metamorphosis tremendous changes occur in silkworm cuticle where multiple proteins exist and genes encoding them constitute about 1.5% of all Bombyx mori genes. Results: In an effort to determine their expression profiles, a microarray-based investigation was carried out using mRNA collected from larvae to pupae. The results showed that a total of 6676 genes involved in various functions and physiological pathways were activated. The vast majority (93%) of cuticular protein genes were expressed in selected stages with varying expression patterns. There was no correlation between expression patterns and the presence of conserved motifs. Twenty-six RR genes distributed in chromosome 22 were co-expressed at the larval and wandering stages. The 2 kb upstream regions of these genes were further analyzed and three putative elements were identified. Conclusions: Data from the present study provide, for the first time, a comprehensive expression profile of genes in silkworm epidermal tissues and evidence that putative elements exist to allow massive production of mRNAs from specific cuticular protein genes. [ABSTRACT FROM AUTHOR]

Background: The natural product Emodin demonstrates a wide range of pharmacological properties including anticancer, anti-inflammatory, antiproliferation, vasorelaxant and anti-H. pylori activities. Although its H. pylori inhibition was discovered, no acting target information against Emodin has been revealed to date. Results: Here we reported that Emodin functioned as a competitive inhibitor against the recombinant β-hydroxyacyl-ACP dehydratase from Helicobacter pylori (HpFabZ), and strongly inhibited the growth of H. pylori strains SS1 and ATCC 43504. Surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) based assays have suggested the kinetic and thermodynamic features of Emodin/HpFabZ interaction. Additionally, to inspect the binding characters of Emodin against HpFabZ at atomic level, the crystal structure of HpFabZ-Emodin complex was also examined. The results showed that Emodin inhibition against HpFabZ could be implemented either through its occupying the entrance of the tunnel or embedding into the tunnel to prevent the substrate from accessing the active site. Conclusion: Our work is expected to provide useful information for illumination of Emodin inhibition mechanism against HpFabZ, while Emodin itself could be used as a potential lead compound for further anti-bacterial drug discovery. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are expressed by a wide range of eukaryotic organisms, and function in diverse biological processes. Numerous miRNAs have been identified in Bombyx mori, but the temporal expression profiles of miRNAs corresponding to each stage transition over the entire life cycle of the silkworm remain to be established. To obtain a comprehensive overview of the correlation between miRNA expression and stage transitions, we performed a whole-life test and subsequent stage-by-stage examinations on nearly one hundred miRNAs in the silkworm. Results: Our results show that miRNAs display a wide variety of expression profiles over the whole life of the silkworm, including continuous expression from embryo to adult (miR-184), up-regulation over the entire life cycle (let-7 and miR-100), down-regulation over the entire life cycle (miR-124), expression associated with embryogenesis (miR-29 and miR-92), up-regulation from early 3rd instar to pupa (miR-275), and complementary pulses in expression between miR-34b and miR-275. Stage-by-stage examinations revealed further expression patterns, such as emergence at specific time-points during embryogenesis and up-regulation of miRNA groups in late embryos (miR-1 and bantam), expression associated with stage transition between instar and molt larval stages (miR-34b), expression associated with silk gland growth and spinning activity (miR-274), continuous high expression from the spinning larval to pupal and adult stages (miR-252 and miR-31a), a coordinate expression trough in day 3 pupae of both sexes (miR-10b and miR-281), up-regulation in pupal metamorphosis of both sexes (miR-29b), and down-regulation in pupal metamorphosis of both sexes (miR-275). Conclusion: We present the full-scale expression profiles of miRNAs throughout the life cycle of Bombyx mori. The whole-life expression profile was further investigated via stage-by-stage analysis. Our data provide an important resource for more detailed functional analysis of miRNAs in this animal. [ABSTRACT FROM AUTHOR]

Background: Diabetic nephropathy (DN) is a chronic condition resulting from microangiopathy in a high-glucose environment. The evaluation of vascular injury in DN has primarily focused on active molecules of VEGF, namely VEGFA and VEGF2(F2R). Notoginsenoside R1 (NGR1), a traditional anti-inflammatory medication, exhibits vascular activity. Therefore, identifying classical drugs with vascular inflammatory protection for the treatment of DN is a valuable pursuit. Methods: The "Limma" method was employed to analyze the glomerular transcriptome data, while the Spearman algorithm for Swiss target prediction was utilized to analyze the drug targets of NGR1. The molecular docking technique was employed to investigate the relationship between vascular active drug targets, and the COIP experiment was conducted to verify the interaction between fibroblast growth factor 1 (FGF1) and VEGFA in relation to NGR1 and drug targets. Results: According to the Swiss target prediction, the LEU32(b) site of the Vascular Endothelial Growth Factor A (VEGFA) protein, as well as the Lys112(a), SER116(a), and HIS102(b) sites of the Fibroblast Growth Factor 1 (FGF1) protein, are potential binding sites for NGR1 through hydrogen bonding. Additionally, the Co-immunoprecipitation (COIP) results suggest that VEGFA and FGF1 proteins can interact with each other, and NGR1 can impede this interaction. Furthermore, NGR1 can suppress the expression of VEGFA and FGF1 in a high-glucose environment, thereby decelerating podocyte apoptosis. Conclusion: The inhibition of the interaction between FGF1 and VEGFA by NGR1 has been observed to decelerate podocyte apoptosis. [ABSTRACT FROM AUTHOR]

Background: The self-rated health of older adults (SHOA) plays an important role in enhancing their medical service utilization and quality of life. However, the determinants and magnitude variations in SHOA at the family level (SHOAFL) remain unknown. The purpose of this study was to assess the status and equitable level of SHOAFL in China, as well as to analyze the influencing factors and the precise nature and scope of their impacts. Methods: This study analyzed the data from the "Chinese residents' health service needs survey in the New Era", and included a total of 1413 families with older adults. The status and influencing factors of SHOAFL were analyzed using mean comparison and Logistic regression (LR) models. The Concentration Index method was used to explore the equity of the distribution of SHOAFL. The relationship between differences in personal characteristics among family members and differences in SHOA was determined by the method of Coupling Coordination Degree (CCD). Results: The total score of SHOAFL was 66.36 ± 15.47, and LR results revealed that the factors with a significant impact on SHOAFL were number of people living in family, distance to the nearest medical service institution, travel time to the nearest medical service institution, annual family income, yearly family medical and health expenditures, average age, and residence (all P < 0.05). The Concentration index of SHOAFL ranged from -0.0315 to 0.0560. CCD of the differences between SHOA and medical insurance and smoking status were 0.9534 and 0.7132, respectively. Conclusion: The SHOAFL was found to be generally but more inclined towards urban families with high incomes and a short time to medical service institution. The observed disparities in SHOA among family members were mostly attributable to differences in health insurance and pre-retirement occupations. The status and equality of SHOAFL may be improved if policymakers prioritize making services more accessible to older rural residents with low incomes. Concurrently, reducing the existing discrepancy in health insurance coverage between older couples may also enhance their health. [ABSTRACT FROM AUTHOR]

Background: Meeting the demands of older adults for health promotion services (DOAHPS) is essential for maintaining their health and enhancing their quality of life. The purpose of this study was to construct a model for evaluating DOAHPS to quantitatively evaluate the current state and equity level of DOAHPS in China, as well as to explore the main factors affecting DOAHPS' current state and equity level. Methods: This study analyzed the DOAHPS data from the "Survey on Chinese Residents' Health Service Demands in the New Era", which included 1542 older adults aged 65 and older. Relationships between evaluation indicators of DOAHPS were explored using Structural Equation Modeling (SEM). The Weighted TOPSIS method and Logistic regression (LR) were used to analyze the current state and factors impacting DOAHPS. The equity level of DOAHPS' allocation among different older adult groups and its influencing factors were determined using the Rank Sum Ratio (RSR) method and T Theil index. Results: The evaluation score for DOAHPS was 42.57 ± 1.51. Health status, health literacy and behavior were positively correlated with DOAHPS (r = 0.40, 0.38; P < 0.05). The LR results revealed that the most significant determinants of DOAHPS were sex, residence, education level and pre-retirement occupation (all P < 0.05). The number of older adults with very poor, poor, general, high and very high level health promotion service demands accounted for 2.27%, 28.60%, 53.05%, 15.43% and 0.65%, respectively. The total T Theil index of DOAHPS was 2.7433*10–4, and the intra-group difference contribution rate exceeded 72%. Conclusions: Compared to the maximum level, the total DOAHPS level was found to be moderate, although the demands of urban seniors with higher levels of education may be substantially greater. The observed inequities in the allocation of DOAHPS were primarily related to differences in education level and pre-retirement occupation within group. To better address health promotion services for older adults, policymakers could target older males with low education who reside in rural regions. [ABSTRACT FROM AUTHOR]

Inhibitory, interneuronal networks are known to underlie high-frequency (gamma, 40-80 Hz) population oscillations, and they are also known to underlie low-frequency rhythms. For example, spontaneous, slow (0.5-4 Hz) rhythms occur in rodent hippocampus. However, it is unclear whether an inhibitory network can generate population oscillations much slower than the intrinsic firing frequencies of its constituent neurons. Here we show that an inhibitory network model in the absence of any slow processes is able to produce low-frequency rhythms. To obtain this, we bridge our network model simulations with a dynamical mean-field (DMA) model to approximate the location of relevant parameter regimes. The individual interneuron model is a two-dimensional conductance-based model and the network is formed with fast, inhibitory GABAA type synapses. The DMA model representing a large all-to-all coupled system consists of 30 equations that include equations describing synaptic noises. Bifurcation analysis is used to explore the DMA model, in particular, to identify parameter regimes for which bursting activities occur. These parameters are used in network simulations. The network model consists of an all-to-all coupled network of 20 interneurons. Each interneuron is described by: CdV/dt = Iapp + bη-gL(V-EL)- gNam(V-ENa)-gKn(V-EK)-gsyn(V-Esyn) ∑isi; m(V) = 1/(1+exp(- 4/3-V/15)); dn/dt = 1/(1+exp(-5-V/5))-n; dsi/dt=a(1-si)/ (1+exp(-Vi/2))-si/τ, where ∑isi sums the (inhibitory) synaptic gating variables from other interneurons in the network, η represents white noise of unit strength and b represents the strength of the noise. Figure 1 shows a raster plot from a 30 second network simulation (left) with the corresponding average summated synaptic activities (right). The parameters used are taken from identified bursting regimes in the DMA model analysis. Parameters values: Iapp= 4.8 µA/cm²; b= 0.08 ms1/2mA/cm²; gL= 8 mS/ cm²; gK= 10 mS/cm²; gNa= 20 mS/cm²; gsyn= 0.0263 mS/ cm²; EL= -80 mV; EK= -90 mV; ENa= 60 mV; Esyn= -85 mV; τ = 10 ms; C = 1 µF/cm². The intrinsic firing frequency at Iapp = 4.8 µA/cm² for these neurons (with zero noise) is 52 Hz. Slow population rhythms (approx 0.5 Hz), or bursts of synaptic activities, can be seen to emerge due to a "switching" between sparsely firing and coherently firing network states. A DMA model analysis has been used to find parameter regimes that allow slow rhythms to be expressed by inhibitory network models. These regimes are identified by bursting activities in a simpler mean-field model. Given the bridging used between the DMA model and the network simulations, we expect that this slow pattern should also occur in much larger network models. We have previously obtained values for synaptic "noise" parameters underlying slow hippocampal rhythms. It will be interesting to determine whether bursting in the DMA models, and thus slow population rhythms in large network simulations, occur using these experimentally-based synaptic noise parameter values. If so, this would suggest a novel way in which slow rhythms could emerge in biological, inhibitory networks. [ABSTRACT FROM AUTHOR]

The article summarizes the results of a study on the role of neural inhibition in shaping the in vitro spontaneous hippocampal network rhythms of rodents. It has found a link between the transition from the quiescent to the rhythmic state of spontaneous rhythmic field potentials (SRFPs) and inhibitory conductance dominance with inhibitory fluctuations of over 10%. It concludes that SRFPs are inhibitory-based rhythms. The quiescent state is also inihibitory dominant.

Background: Cumulating evidence has shown a close correlation between electroacupuncture stimulation (EAS) frequency-specific analgesic effect and central opioid peptides. However, the actions of hippocampal acetylcholinergic receptors have not been determined. This study aims to observe the effect of different frequencies of EAS on the expression of hippocampal muscarinic and nicotinic acetylcholinergic receptors (mAChRs, nAChRs) in neuropathic pain rats for revealing their relationship. Methods: Forty male Wistar rats were randomly and equally divided into sham, CCI model, 2, 2/15 and 100 HzEA groups. The neuropathic pain model was established by ligature of the left sciatic nerve to induce chronic constriction injury (CCI). EAS was applied to bilateral Zusanli (ST36) and Yanglingquan (GB34) for 30 min, once daily for 14 days except weekends. The mechanical pain thresholds (withdrawal latencies, PWLs) of bilateral hindpaws were measured. The expression levels of hippocampal M1 and M2 mAChR, and α4 and β2 nAChR genes and proteins were detected by quantitative RT-PCR and Western blot, separately. The involvement of mAChR and nAChR in the analgesic effect of EAS was confirmed by intra-hippocampal microinjection of M1mAChR antagonist (Pirenzepine) and α4β2 nAChR antagonist (dihydro-beta-erythroidine) respectively. Results: Following EAS, the CCI-induced increase of difference values of bilateral PWLs on day 6 and 14 was significantly reduced (P < 0.05), with 2/15 Hz being greater than 100 Hz EAS on day 14 (P < 0.05). After 2 weeks' EAS, the decreased expression levels of M1 mAChR mRNA of both 2 and 2/15 Hz groups and M1 mAChR protein of the three EAS groups, α4 AChR mRNA of the 2/15 Hz group and β2 nAChR protein of the three EAS groups were considerably increased (P < 0.05), suggesting an involvement of M1 mAChR and β2 nAChR proteins in EAS-induced pain relief. No significant changes were found in the expression of M2 mAChR mRNA and protein, α4 nAChR protein and β2 nAChR mRNA after CCI and EAS (P > 0.05). The analgesic effect of EAS was abolished by intra-hippocampal microinjection of M1mAChR and α4β2 nAChR antagonists respectively. Conclusions: EAS of ST36-GB34 produces a cumulative analgesic effect in neuropathic pain rats, which is frequency-dependent and probably mediated by hippocampal M1 mAChR and β2 nAChR proteins. [ABSTRACT FROM AUTHOR]

Background: Polystichum (Dryopteridaceae) is probably the third largest fern genus in the world and contains ca. 500 species. Species of Polystichum occur on all continents except Antarctica, but its highest diversity is found in East Asia, especially Southwest China and adjacent regions. Previous studies typically had sparse taxon sampling and used limited DNA sequence data. Consequently, the majority of morphological hypotheses/classifications have never been tested using molecular data. Results: In this study, DNA sequences of five plastid loci of 177 accessions representing ca. 140 species of Polystichum and 13 species of the closely related genera were used to infer a phylogeny using maximum likelihood, Bayesian inference, and maximum parsimony. Our analyses show that (1) Polystichum is monophyletic, this being supported by not only molecular data but also morphological features and distribution information; (2) Polystichum is resolved into two strongly supported monophyletic clades, corresponding to the two subgenera, P. subg. Polystichum and P. subg. Haplopolystichum; (3) Accessions of P. subg. Polystichum are resolved into three major clades: clade K (P. sect. Xiphophyllum), clade L (P. sect. Polystichum), and the HYMASO superclade dominated by accessions of P. sect. Hypopeltis, P. sect. Macropolystichum, and P. sect. Sorolepidium, while those of P. subg. Haplopolystichum are resolved into eight major clades; and (4) The monophyly of the Afra clade (weakly supported), the Australasian clade (weakly supported), and the North American clade (strongly supported) is confirmed. Conclusions: Of the 23 sections of Polystichum recognized in a recent classification of the genus, four (P. sect. Hypopeltis, P. sect. Neopolystichum, P. sect. Sorolepidium, P. sect. Sphaenopolystichum) are resolved as non-monophyletic, 16 are recovered as monophyletic, and three are monospecific. Of the 16 monophyletic sections, two (P. sect. Adenolepia, P. sect. Cyrtogonellum) are weakly supported and 14 are strongly supported as monophyletic. The relationships of 11 sections (five in P. subg. Haplopolystichum; six in P. subg. Polystichum) are well resolved. [ABSTRACT FROM AUTHOR]

A correction to the article "MicroRNA Expression Profiling During the Life Cycle of the Silkworm (Bombyx mori)" published in a previous issue of the journal is presented.

Interruption of the descending aorta is an extremely rare great vessel malformation. In this report, we describe a very unusual case of a 29-year-old female with a 13-year history of hypertension who was found to have an interruption of the descending aorta when she was hospitalized with a subarachnoid hemorrhage and symptoms of acute paraplegia. We successfully surgically corrected the defect using a Gore-Tex® graft to bypass the aortic interruption. The patient's blood pressure postoperatively returned to normal, and the patient recovered completely from her paraplegia by the time of her 5-month follow-up visit. [ABSTRACT FROM AUTHOR]

Interruption of the descending aorta is an extremely rare great vessel malformation. In this report, we describe a very unusual case of a 29-year-old female with a 13-year history of hypertension who was found to have an interruption of the descending aorta when she was hospitalized with a subarachnoid hemorrhage and symptoms of acute paraplegia. We successfully surgically corrected the defect using a Gore-Tex® graft to bypass the aortic interruption. The patient’s blood pressure postoperatively returned to normal, and the patient recovered completely from her paraplegia by the time of her 5-month follow-up visit. [ABSTRACT FROM AUTHOR]

Background: Human Borna disease virus (BDV) infections have recently been reported in China. BDV causes cognitive and behavioural disturbances in animals. The impact on human mental disorders is subject to debate, but previous studies worldwide have found neuropsychiatric patients more frequently infected than healthy controls. A few isolates were recovered from severely depressed patients, but contagiousness of BDV strain remains unknown. Method: We addressed the risk of infection in health care settings at the first affiliated hospital of Chongqing Medical University (CQMU), located in downtown Chongqing, a megacity in Southwest China. Between February 2012 and March 2013, we enrolled 1529 participants, of whom 534 were outpatients with major depressive disorder (MDD), 615 were hospital personnel, and 380 were healthy controls who underwent a health check. Infection was determined through BDV-specific circulating immune complexes (CIC), RNA, and selective antibodies (blood). Results: One-fifth of the hospital staff (21.8%) were found to be infected (CIC positive), with the highest prevalence among psychiatry and oncology personnel, which is twice as many as were detected in the healthy control group (11.1%), and exceeds the prevalence detected in MDD patients (18.2%). Conclusion: BDV circulates unnoticed in hospital settings in China, putting medical staff at risk and warranting clarification of infection modes and introduction of prevention measures. [ABSTRACT FROM AUTHOR]

Background: Over the last decade, emerging research methods, such as comparative genomic analysis and phylogenetic study, have yielded new insights into genotypes and phenotypes of closely related bacterial strains. Several findings have revealed that genomic structural variations (SVs), including gene gain/loss, gene duplication and genome rearrangement, can lead to different phenotypes among strains, and an investigation of genes affected by SVs may extend our knowledge of the relationships between SVs and phenotypes in microbes, especially in pathogenic bacteria. Results: In this work, we introduce a 'Genome Topology Network' (GTN) method based on gene homology and gene locations to analyze genomic SVs and perform phylogenetic analysis. Furthermore, the concept of 'unfixed ortholog' has been proposed, whose members are affected by SVs in genome topology among close species. To improve the precision of 'unfixed ortholog' recognition, a strategy to detect annotation differences and complete gene annotation was applied. To assess the GTN method, a set of thirteen complete M. tuberculosis genomes was analyzed as a case study. GTNs with two different gene homology-assigning methods were built, the Clusters of Orthologous Groups (COG) method and the orthoMCL clustering method, and two phylogenetic trees were constructed accordingly, which may provide additional insights into whole genome-based phylogenetic analysis. We obtained 24 unfixable COG groups, of which most members were related to immunogenicity and drug resistance, such as PPE-repeat proteins (COG5651) and transcriptional regulator TetR gene family members (COG1309). Conclusions: The GTN method has been implemented in PERL and released on our website. The tool can be downloaded from http://homepage.fudan.edu.cn/zhouyan/gtn/, and allows re-annotating the 'lost' genes among closely related genomes, analyzing genes affected by SVs, and performing phylogenetic analysis. With this tool, many immunogenic-related and drug resistance-related genes were found to be affected by SVs in M. tuberculosis genomes. We believe that the GTN method will be suitable for the exploration of genomic SVs in connection with biological features of bacterial strains, and that GTN-based phylogenetic analysis will provide additional insights into whole genome-based phylogenetic analysis. [ABSTRACT FROM AUTHOR]

Introduction: Within China's multi-tiered medical system, many patients seek care in higher-tiered hospitals without a referral by a primary-care provider. This trend, generally referred to as patient self-referral behavior, may reduce the efficiency of the health care system. This study seeks to test the hypothesis that having a usual primary care provider could reduce patients' self-referral behavior.Methods: We obtained medical records of 832 patients who were hospitalized for common respiratory diseases from township hospitals in Qianjiang District of Chongqing City during 2012-2014. Logit regressions were performed to examine the association between having a township hospital as a usual provider and self-referring to a county hospital after being discharged from a township hospital, while controlling for patients' gender, age, income, education, severity of disease, distance to the nearest county hospital and the general quality of the township hospitals in their community. A propensity score weighting approach was applied.Results: We found that having a usual primary care provider was associated with a lower likelihood of self-referral (odds ratio = 0.58, 95% confidence interval [CI] =0.41-0.82), and a 9% (95% CI: -14%, - 3%) reduction in the probability of patients' self-referral behavior.Discussion/conclusion: The results suggest that establishing a long-term relationship between patients and primary care providers may enhance the patient-physician relationship and reduce patients' tendency for unnecessary use of medical resources. [ABSTRACT FROM AUTHOR]

Background: It remains an urgent need for early recognition of disease severity, treatment option and outcome of Guillain-Barré syndrome (GBS). The chief complaint may be quickly obtained in clinic and is one of the candidates for early predictors. However, studies on the chief complaint are still lacking in GBS. The aim of the study is to describe the components of chief complaints of GBS patients, and to explore association between chief complaints and disease severity/treatment option/outcome of GBS, so as to aid the early prediction of the disease course and to assist the clinicians to prescribe an optimal early treatment.Methods: A total of 523 GBS patients admitted to the First Hospital of Jilin University from 2003 to 2013 were enrolled for retrospective analysis. The data of chief complaints, clinical manifestations, and treatment options, etc. were collected. The clinical severity was evaluated by the Medical Research Council sum score and the Hughes Functional Grading Scale. The prognosis at 6 month after discharge was described by modified Erasmus GBS outcome score. The clinic GBS severity evaluation scale (CGSES), a newly established model in our study, was used to explore the role of chief complaints to predict intravenous immunoglobulin (IVIg).Results: The major components of the chief complaints of GBS patients were weakness, numbness, pain, cranial nerve involvement, dyspnea, ataxia and autonomic dysfunction. Chief complaint of weakness was a predictor of severe disease course and poor short-term outcome, while chief complaint of numbness and cranial nerve involvement were promising predictors. Cranial nerve involvement was the predictor of ventilator dependence. The percentages of 366 GBS patients, who need IVIg treatment at nadir with CGSES ranging from 1 to 4, were 50.00, 67.34, 80.61, and 90.67%, respectively.Conclusions: Chief complaints are clinic predictors of disease severity, ventilator dependence and short-term outcome. IVIg treatment during hospitalisation could be predicted in clinic using CGSES score. [ABSTRACT FROM AUTHOR]

Background: Triatomines, also known as kissing bugs, which are found throughout the world and especially in Latin America, are well known natural vectors that transmit American trypanosomiasis, also called Chagas disease. In China, the presence of two species of Triatoma (Triatoma rubrofasciata and T. sinica) was recorded in the past. Due to the growing population and the increasing risk of the global spread of Chagas disease, triatomines became a potential public health nuisance, and in 2016, we started monitoring triatomine activities in southern China. Methods: Triatomine specimens were collected by the National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, and identified by their morphological characteristics under a dissecting microscope. In addition to morphological analysis, the genomic DNA of the specimens was extracted, and the mitochondrial 16S rRNA, the cytochrome b (CytB) gene and the nuclear ribosomal 28S rRNA gene were PCR-amplified to analyze and confirm the species genetically. Results: One female adult insect and one male adult insect were collected in a dwelling in the rural area of Shunde County, Foshan City, Guangdong Province, China (22°42'44.63"N, 113°08'45.34"E). The results from the morphological and genetic analyses indicated that these triatomines were T. rubrofasciata. Conclusions: This is the first time that the occurrence of T. rubrofasciata has been confirmed in Foshan City, Guangdong Province in southern China. Further studies are needed to reach a clearer understanding of the ecology of this species of triatomine, since it has been found to be naturally infected by Trypanosoma cruzi and T. conorhini and there is evidence of its domiciliation capabilities. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a common and frequently occurring chronic disease of the cardiovascular system. Besides the pathological factors, the occurrence and exacerbation of hypertension are also associated with many factors of lifestyle and behaviors. Thus hypertensive patients' Health-related quality of life (HRQL) is not only influenced by the disease itself but also by many subjective factors such as health literacy and self-management efficacy, especially in the deeper part of southwestern China and thus is less developed compared to the other places. The purpose of this study was to examine the association between the HRQL of hypertensive patients and health literacy and self-management efficacy as well as how they affect the HRQL, so as to provide a theoretical reference for improving the HRQL of patients with hypertension in less developed areas. Methods: This was a cross-sectional study of baseline data from a clustered randomized controlled trial. The study design had passed a cross-national peer review and accepted grants by the China Medical Board. It was also registered in the Chinese Clinical Trial Registry (ChiCTR-OOR-14005563). A standardized questionnaire adapted from a previous validated WHO questionnaire was used for the survey which included detailed questions about patient's socio-demographic characteristics and self-reported information. Patients' HRQL was measured by the Mandarin version of the 36-item Short Form. We used the validated Mandarin version of the Self-Efficacy for Managing Chronic Disease 6-Item Scale to assess patients' self-management efficacy. The validated three-item Brief Health Literacy Screening (BHLS) was used to measure the patients' health literacy. A structural equation model was constructed, and p ≤ 0.05 was taken as significant. Results: Demographic characteristics, health literacy and self-management efficacy have all significant effects on HRQL. Age, education level, self-management efficacy and health literacy were significantly related to the HRQL. The constructed model had a good fit for the data according to the model fit indices. Based on the model, health literacy (r = 0.604, p = 0.029) and Self-management efficacy (r = 0.714, p = 0.018) have a significant impact on HRQL. Demographic characteristics were inversely related to HRQL (r = -0.419, p = 0.007), but have a significant impact on health literacy (r = 0.675, p = 0.029) and self-management efficacy (r = 0.379, p = 0.029). At the same time, self-management efficacy was positively correlated to health literacy (r = 0.413, p <0.01). Conclusions: Age, education level, self-management efficacy and health literacy were all related to the HRQL of patient with hypertension, which means that patients who are more elderly and have lower education level, low self-management efficacy and poor health literacy get worse HRQL. This may imply the necessary to introduce routine assessment of health literacy and self-management efficacy into assessment procedures for hypertensive patients' health management. Such assessment can help professionals to identify the population at greatest risk for poor health outcomes and low well-being in the future. In clinical practice, effective interventions such as direct guidance and education to raise the self-management efficacy and enhance health literacy might improve the HRQL of patients with hypertension. Trial registration: Retrospectively registered Chinese Clinical Trial Registry (ChiCTR-OOR-14005563). Name of registry: Effects of the integrated delivery system and payment system of community-based intervention on rural patients of chronic diseases in Qianjiang District, China Date of registration: Retrospectively registered 23 November 2014. Date of enrolment of the first participant to the trial: 5 July 2012 [ABSTRACT FROM AUTHOR]

Background: Homeobox B7 (HOXB7) has been identified associated with poor prognosis of hepatocellular carcinoma (HCC). However, the specific mechanism by which HOXB7 promotes the malignant progression of HCC remains to be determined. Methods: Immunohistochemistry (IHC) was used to detect the expression level of HOXB7 in 77-paired HCC tissue samples, and the correlation between HOXB7 and HCC prognosis was assessed. The location of HOXB7 was confirmed by immunofluorescence. Cell Titer-Blue assay was used to assess the proliferation of hepatoma cells. The stem-like properties of hepatoma cells were analysed by sphere formation and clone formation assays. The effect of HOXB7 on expression of cancer stem cell markers was evaluated. Transwell and woundhealing assays were performed to estimate the invasion and migration abilities of hepatoma cells. A xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth. Bioluminescence imaging was used to survey the effect of HOXB7 on the metastatic ability of hepatoma cells in vivo. Results: Higher expression of HOXB7 was detected in HCC tissues compared with noncancerous tissues and significantly associated with poor prognosis of HCC. In addition, HOXB7 knockdown suppressed the cell proliferation, clone formation, sphere formation, invasion and migration of hepatoma cells in vitro; conversely, these biological abilities of hepatoma cells were enhanced by HOXB7 overexpression. Moreover, the cancer stem cell markers EPCAM and NANOG were up-regulated by HOXB7. The role of HOXB7 in promoting tumor growth and metastasis was verified in vivo. Further investigation revealed that c-Myc and Slug expression was elevated by HOXB7 and the AKT pathway was activated. Conclusion: Overexpression of HOXB7 was significantly correlated with poor prognosis of HCC. HOXB7 up-regulated c-Myc and Slug expression via the AKT pathway to promote the acquisition of stem-like properties and facilitate epithelial-mesenchymal transition of hepatoma cells, accelerating the malignant progression of HCC. [ABSTRACT FROM AUTHOR]

Background: Milk is a complex liquid that provides nutrition to newborns. Recent reports demonstrated that milk is enriched in maternal-derived exosomes that are involved in fetal physiological and pathological conditions by transmission of exosomal mRNAs, miRNAs and proteins. Until now, there is no such research relevant to exosomal mRNAs and proteins in porcine milk, therefore, we have attempted to investigate porcine milk exosomal mRNAs and proteins using RNA-sequencing and proteomic analysis. Results: A total of 16,304 (13,895 known and 2,409 novel mRNAs) mRNAs and 639 (571 known, 66 candidate and 2 putative proteins) proteins were identified. GO and KEGG annotation indicated that most proteins were located in the cytoplasm and participated in many immunity and disease-related pathways, and some mRNAs were closely related to metabolisms, degradation and signaling pathways. Interestingly, 19 categories of proteins were tissuespecific and detected in placenta, liver, milk, plasma and mammary. COG analysis divided the identified mRNAs and proteins into 6 and 23 categories, respectively, 18 mRNAs and 10 proteins appeared to be involved in cell cycle control, cell division and chromosome partitioning. Additionally, 14 selected mRNAs were identified by qPCR, meanwhile, 10 proteins related to immunity and cell proliferation were detected by Western blot. Conclusions: These results provide the first insight into porcine milk exosomal mRNA and proteins, and will facilitate further research into the physiological significance of milk exosomes for infants. [ABSTRACT FROM AUTHOR]

Background: Prepulse inhibition (PPI) and attention were impaired, which may cause psychotic symptoms and (or) hinder the cognitive functions in schizophrenia. However, due to the measurement methods of PPI, findings about the relationship between PPI and clinical symptoms, cognitive performances have been equivocal. Methods: Seventy-five schizophrenia patients (SZ) and 50 healthy controls (HC) were assessed in a modified acoustic PPI paradigm, named perceived spatial separation-induced PPI (PSS-PPI), compared to perceived spatial co-location PPI (PSC-PPI) with inter-stimulus interval (ISI) of 120 ms. Repeatable Battery for the Assessment of Neuropsychological Status and the Stroop Color-Word Test were administered to all subjects. Results: Significant decrease in the modified PPI was found in the patients as compared to the controls, and effect sizes (Cohen'd) for patients vs. HCs % PPI levels achieved a significant level (PSC-PPI d = 0.84, PSS-PPI d = 1.27). A logistic regression model based on PSS-PPI significantly represented the diagnostic grouping (χ2 = 29.3; p < 0.001), with 85.2% area under ROC curve in predicting group membership. In addition, patients exhibited deficits in neurocognition. Among patients of "non-remission", after controlling for gender, age, education, duration, recurrence times, onset age, cigarettes per day and chlorpromazine equivalent dosage, PSS-PPI levels were associated with positive and negative symptoms, PANSS total and thought disorder (P1, P6, P7, N5, N7, G9). In multiple linear regression analyses, male and higher attention scores contributed to better PSC-PPI and PSS-PPI in controls group, while larger amount of smoke and longer word-color interfere time contributed to poor PSS-PPI. In patients' group, higher education and attention scores contributed to better PSS-PPI, while repeated relapse contributed to poor PSS-PPI. Conclusions: The acoustic perceived spatial separation-induced PPIs may bring to light the psychopathological symptoms, especially for thought disorder, and the mechanism(s) of the novel PPI paradigm was associated with attention function. [ABSTRACT FROM AUTHOR]

Background: Hypertension affects one billion people globally and is one of the leading risk factors for cardiovascular and renal diseases. However, hypertension management remains poor, especially in rural China.Methods: A clustered randomized controlled trial was conducted in six towns in China's Qianjiang county between 7/2012 and 6/2014, including 5462 hypertension patients above 35 years old. Six towns were randomly assigned to three groups: Group 1 had the integrated care model including a multidisciplinary team and continuous care coordination, Group 2 had both the integrated care model and provider-level financial incentives, and the control group had the usual care. Primary outcomes were systolic blood pressure and health-related quality of life measured by SF36; secondary outcomes included hypertension-related hospitalization rate and inpatient spending. Blood pressure was measured sixteen times bimonthly between 12/1/2011 and 6/30/2014, and quality of life was measured on 7/1/2012 and 6/30/2014. Inpatient data between 7/1/2010 and 8/31/2014 were used. This trial is registered at the World Health Organization's International Clinical Trials Registry, number ChiCTR-OOR-14005563.Results: We found that the integrated care model effectively lowered blood pressure by 1.93 mmHg (95% CI 0.063-3.8), improved self-assessed health-related quality of life, and reduced the rate of hypertension-related hospitalization by 0.17 percentage points (95% CI 0.094-0.24). We also found that the provider-level financial contract further lowered blood pressure by 1.76 mmHg (95% CI 0.73-2.79) and reduced rates of hospitalization and inpatient spending, but it also reduced patients' self-assessed health-related quality of life.Conclusions: Integrated care and financial incentives are effective in lowering blood pressure and reducing hospitalization rate, but financial contracts may hurt patient quality of life. This trial was registered at the Chinese Clinical Trial Registry (ChiCTR-OOR-14005563) on November 23, 2014. It was a retrospective registration. [ABSTRACT FROM AUTHOR]

Background: Umbilical cord blood (UCB) not only contains hematopoietic stem cells (HSCs), but also non-hematopoietic stem cells (NHSCs) that are able to differentiate into a number of distinct cell types. Based on studies published to date, the frequency of NHSCs in UCB is believed to be very low. However, the isolation of these cells is primarily based on their adhesion to tissue culture plastic surfaces. Methods and results: In the current study, we demonstrate that this approach overlooks some of the extremely immature NHSCs because they lack the ability to adhere to plastic. Using a native extracellular matrix (ECM), produced by bone marrow (BM) stromal cells, the majority of the UCB-NHSCs attached within 4 h. The colony-forming unit fibroblast frequency of these cells was 1.5 x 104/108 mononuclear cells, which is at least 4000-fold greater than previously reported for UCB-NHSCs. The phenotype of these cells was fibroblast-like and different from those obtained by plastic adhesion; they formed embryonic body-like clusters that were OCT4-positive and expressed other human embryonic stem cell-related markers. Importantly, when implanted subcutaneously for 8 weeks into immunocompromised mice, these ECM-adherent and expanded NHSCs generated three germ layer-derived human tissues including muscle, fat, blood vessel, bone, gland, and nerve. Moreover, injection of these cells into muscle damaged by cryoinjury significantly accelerated muscle regeneration. Conclusions: These results indicate that UCB may be a virtually unlimited source of NHSCs when combined with isolation and expansion on ECM. NHSCs may be a practical alternative to embryonic stem cells for a number of therapeutic applications. [ABSTRACT FROM AUTHOR]

Background: Continuity of care is widely considered a principle of primary care that decreases healthcare utilization and mortality. However, the effect of continuity of care on health-related quality of life (HRQoL) for adult patients with hypertension remains unclear. Methods: To further evaluate the effect of continuity of care, we implemented a cohort study among hypertensive patients aged over 35 years (n = 1200) in six townships in Qianjiang District, Chongqing, China, between 2012 and 2014. The study ultimately included 1079 participants. The continuity of care index was calculated using claim-based longitudinal data obtained from hypertension follow-up service records. The baseline and endline survey-based data, tested by the SF-36 scale, were used to assess HRQoL. To control selection bias and examine the effect of continuity of care, a kernel-based propensity score matching difference-in-differences (DID) method was used. Additionally, descriptive statistics, chi-squared test, and Mann-Whitney nonparametric test were used to summarize characteristics, evaluate proportional differences, and analyze statistical differences, respectively. Results: Our results showed that patients in the high continuity of care group presented greater improvement in both Physical Component Summary (PCS, DID = 5.192 ± 1.970, p < 0.001) and Mental Component Summary (MCS, DID = 7. 900 ± 1.815, p = 0.008) than those in the low continuity of care group. Moreover, patients in the high continuity of care group showed significant improvement in physical functioning, role-physical, general health, role-emotional, and mental health. Conclusions: Our findings indicate that a long-term physician-patient relationship may improve HRQoL in patients with hypertension. However, more unified measurement tools are needed to evaluate continuity of care. Further studies should include more study settings. [ABSTRACT FROM AUTHOR]

Background: Modified Erxian decoction (MEXD), i.e., Erxian decoction (EXD) with Fructus Schisandrae chinensis (Wu Wei Zi) added, has been used to alleviate menopausal symptoms. This study aimed to investigate the effects of MEXD on menopausal sweating and serum hormone levels in a rat model of menopause after oral administration of MEXD. Methods: Quality control of MEXD was conducted by employing a reversed-phase high performance liquid chromatography column. The three treatment groups received oral administration of MEXD in 0.5% sodium carboxylmethyl cellulose (CMC-Na) at three different doses (5.5, 11, and 22 g/kg body weight) once-daily for 6 consecutive weeks, with 10 animals per group. Huangqijing oral liquor (5 mL/kg) prepared from the roots of Huang qi (Astragalus membranaceus) with an antiperspirant effect was used as a positive control. The negative control group received the same volume of vehicle (0.5% CMC-Na). Ten 3-month-old Sprague-Dawley rats were used as a young group for comparison with the treatment groups (12-14 months old rats). Blood was collected from all animals after 3-6 weeks of treatment. At the end of the treatment, the uterine weight, ovarian weight, and body weight were recorded. Serum malondialdehyde contents and superoxide dismutase activities were determined by thiobarbituric acid colorimetric assays and chemoluminescence assays, respectively. Serum levels of estradiol, follicle-stimulating hormone, and luteinizing hormone were measured by radioimmunoassays. Rat foot pad assays were used to determine the antiper-spirant activity of MEXD and histological examinations were conducted on plantar sweat glands. Results: Treatment with MEXD (11 g/kg) significantly inhibited sweat excretion in the menopause model rats after treatment for 3 (P = 0.0026) and 6 (P < 0.0001) weeks. The decoction markedly decreased the number of secretory cells in plantar sweat glands. In addition, MEXD (11 g/kg) significantly increased the serum estradiol levels (P < 0.001) and superoxide dismutase activities (P = 0.0405). Furthermore, MEXD (11 g/kg) markedly decreased the serum levels of follicle-stimulating hormone (P = 0.001), luteinizing hormone (P = 0.0213), and malondialdehyde (P = 0.01). Conclusion: Modified Erxian decoction significantly inhibited sweat excretion, regulated serum levels of pituitary gonadotropins and estradiol, and exhibited antioxidative effects in a rat model of menopause. [ABSTRACT FROM AUTHOR]

Background: Phosphorus (P), an essential macronutrient, is often limiting in soils and affects plant growth and development. In Arabidopsis thaliana, Low Phosphate Root1 (LPR1) and its close paralog LPR2 encode multicopper oxidases (MCOs). They regulate meristem responses of root system to phosphate (Pi) deficiency. However, the roles of LPR gene family in rice (Oryza sativa) in maintaining Pi homeostasis have not been elucidated as yet. Results: Here, the identification and expression analysis for the homologs of LPR1/2 in rice were carried out. Five homologs, hereafter referred to as OsLPR1-5, were identified in rice, which are distributed on chromosome1 over a range of 65 kb. Phylogenetic analysis grouped OsLPR1/3/4/5 and OsLPR2 into two distinct sub-clades with OsLPR3 and 5 showing close proximity. Quantitative real-time RT-PCR (qRT-PCR) analysis revealed higher expression levels of OsLPR3-5 and OsLPR2 in root and shoot, respectively. Deficiencies of different nutrients ie, P, nitrogen (N), potassium (K), magnesium (Mg) and iron (Fe) exerted differential and partially overlapping effects on the relative expression levels of the members of OsLPR family. Pi deficiency (−P) triggered significant increases in the relative expression levels of OsLPR3 and 5. Strong induction in the relative expression levels of OsLPR3 and 5 in osphr2 suggested their negative transcriptional regulation by OsPHR2. Further, the expression levels of OsLPR3 and 5 were either attenuated in ossiz1 and ospho2 or augmented in rice overexpressing OsSPX1. Conclusions: The results from this study provided insights into the evolutionary expansion and a likely functional divergence of OsLPR family with potential roles of OsLPR3 and 5 in the maintenance of Pi homeostasis in rice. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic partial nephrectomy (LPN) is not a novel but a relatively technically challenging surgical procedure. Off-clamp LPN with zero ischemia can completely eliminate ischemic reperfusion injury to the kidney. The purpose of this study was to evaluate the safety and functional outcome of nephrometry score-guided off-clamp technique in LPN. Methods: A total of 44 patients underwent LPN between January 2015 and July 2015 for renal mass with radius, exophytic/endophytic, nearness to sinus, anterior/posterior location (RENAL) score 4 were enrolled. Twenty-two of them underwent off-clamp LPN with zero ischemia, and the other 22 received standard LPN with common renal artery clamp. Estimate blood loss (EBL), total operation time, resection time, renorrhaphy time, preoperative estimated glomerular filtration rate (eGFR), postoperative eGFR, eGFR change, and drainage after surgery were compared between these two groups using t test. Results: Patients' characteristics including gender, age, BMI, tumor size, and RENAL score were balanced between the two groups. Average EBL was more in the off-clamp group than in the on-clamp group (134.32 versus 70.23 ml, p = 0.001). Average eGFR change was less in the off-clamp group than in the on-clamp group (-1.56 versus -6.45, p < 0.001). Average drainage after surgery was 203.41 ml for the off-clamp group and 145.46 ml for the on-clamp group, p = 0.062. No urinary leakage and hematuria occurred in both groups. There were no statistical difference in total operation time, resection time, renorrhaphy time, preoperative eGFR, and postoperative eGFR between the two groups. Conclusions: Off-clamp LPN is a safe and feasible approach to excise certain kidney tumors with RENAL score 4. This technique can better preserve kidney function without ischemic reperfusion injury. [ABSTRACT FROM AUTHOR]

Background: Karyotyping is the gold standard cytogenetic method for detection of ring chromosomes. In this study we report the molecular characterization of a novel ring 6 (r6) chromosome in a six-year-old girl with severe mental retardation, congenital heart disease and craniofacial abnormalities. Methods: Cytogenetic analysis was performed by conventional karyotyping. Molecular genetic analyses were performed using high-resolution chromosome microarray analysis (CMA) and next generation sequencing (NGS). OMIM, UCSC and PubMed were used as reference databases to determine potential genotype to phenotype associations. Results: Peripheral blood and skin fibroblast karyotyping revealed the presence of a dominant cell line, 46,XX,(r6)(p25.3;q27) and a minor cell line 45,XX,-6. Molecular karyotyping using NGS identified 6p25.3 and 6q27 subtelomeric deletions of 1.78 Mb and a 0.56 Mb, respectively. Based on the known genes located within the r6 deletion interval 6q25.3-pter, genotype to phenotype association studies found compelling evidence to suggest that hemizygous expression of disease genes FOXC1, FOXF2, IRF4 and GMDS was the main underlying cause of the patient's phenotype. We further speculate that the severity of the patient's symptoms may have been exacerbated by low-level instability of the r6 chromosome. Conclusion: This is the first report of a novel r6 chromosome characterized at the molecular level using NGS. [ABSTRACT FROM AUTHOR]

Background: DNA topoisomerase I (Top1) is a DNA unwinding protein and the specific target of the camptothecin class of chemotherapeutic drugs. One of these, irinotecan, acting through its active metabolite SN-38, is used in the treatment of metastatic colorectal cancer. However, resistance to irinotecan represents a major clinical problem. Since molecular alterations in Top1 may result in resistance to irinotecan, we characterized Top1 in three human colon cancer cell lines with acquired resistance to SN-38. Methods: Three SN-38 resistant (20-67 fold increased resistance) cell lines were generated and compared to wildtype parental cells with regards to: TOP1 gene copy number and gene sequence, Top1 expression (mRNA and protein), Top1 enzymatic activity in the absence and presence of drug, and Top1-DNA cleavage complexes in drug treated cells. TOP1 mutations were validated by PCR using mutant specific primers. Furthermore, cross-resistance to two indenoisoquinoline Top1-targeting drugs (NSC 725776 and NSC 743400) and two Top2-targeting drugs (epirubicin and etoposide) was investigated. Results: Two of three SN-38 resistant cell lines carried TOP1 gene copy number aberrations: A TOP1 gene copy gain and a loss of chromosome 20, respectively. One resistant cell line harbored a pair of yet unreported TOP1 mutations (R364K and G717R) in close proximity to the drug binding site. Mutant TOP1 was expressed at a markedly higher level than wild-type TOP1. None or very small reductions were observed in Top1 expression or Top1 activity in the absence of drug. In all three SN-38 resistant cell lines Top1 activity was maintained in the presence of high concentrations of SN-38. None or only partial cross-resistance were observed for etoposide and epirubicin, respectively. SN-38 resistant cells with wild-type TOP1 remained sensitive to NSC 743400, while cells with mutant TOP1 was fully cross-resistant to both indenoisoquinolines. Top1-DNA cleavage complex formation following drug treatment supported the other findings. Conclusions: This study adds to the growing knowledge about resistance mechanisms for Top1-targeting chemotherapeutic drugs. Importantly, two yet unreported TOP1 mutations were identified, and it was underlined that cross-resistance to the new indenoisoquinoline drugs depends on the specific underlying molecular mechanism of resistance to SN-38. [ABSTRACT FROM AUTHOR]