Search

Introduction: The equity of health resource allocation geographically is a contested topic. Sichuan Province, located in Southwest China, has varied topography, providing us with natural materials to explore the determinants of health resource distribution. Materials and methods: Spatial panel econometric models were constructed to explore the relationship between health resources and factors such as health care service demand and socioeconomic and demographic perspectives using data from Sichuan Province for eight consecutive years (2010–2017). Results: Health care service demands were found to be a major driving force behind the distribution of health resources, showing that an increase in health care service demands draws health resources to specific counties and surrounding areas. From a socioeconomic perspective, gross domestic product per capita and the average wage show a positive association with health resources. In addition, the total population and proportion of the urban population have diverse effects in regard to health-related human resources but have the same effects on material and financial health resources. Conclusions: Our results provide the Chinese government with evidence needed to formulate and promulgate effective policies, especially those aiming to tackle inequity among different regions. [ABSTRACT FROM AUTHOR]

Background: Evidence for the preventative effects of percutaneous transluminal angioplasty and stenting (PTAS) on the recurrence of stroke in patients with severe intracranial vertebrobasilar stenoses (IVBS) varies, and the influence of study characteristics on the study outcomes have not been determined. Methods: A study level based meta-analysis was performed to investigate the influence of baseline characteristics on the 30-day and follow-up stroke recurrence or death in symptomatic IVBS patients receiving PTAS. Relevant single center studies were retrieved by searching PubMed and Embase. A random effect model was applied to synthesize the outcomes. Meta-regression and subgroup analyses were performed to evaluate the potential influence of study characteristics on outcomes. Results: Fifteen cohort studies comprising 554 symptomatic IVBS patients were included. PTAS was associated with an 8% incidence of stroke recurrence or death (95% CI: 5% to 12%) in IVBS patients within 30 days, and 8 per 100 person-years (95% CI: 5 to 11 per 100 person-years) of cumulative stroke recurrence or death during follow-up. Meta-regression indicated that the center volume, as defined by the numbers of cases per year, was negatively correlated with 30-day (regression coefficient = -0.09, p = 0.02) and follow-up (regression coefficient = -0.60, p = 0.01) stroke recurrence or death. Age, gender, or comorbidities have no significant effect on the outcomes. Conclusions: Centers of higher procedural volume may be associated with better clinical outcomes for symptomatic IVBS patients receiving PTAS. [ABSTRACT FROM AUTHOR]

Background: China is the largest developing country with a relatively developed public health system. To further prevent and eliminate the spread of infectious diseases, China has listed 39 notifiable infectious diseases characterized by wide prevalence or great harm, and classified them into classes A, B, and C, with severity decreasing across classes. Class A diseases have been almost eradicated in China, thus making class B diseases a priority in infectious disease prevention and control. In this retrospective study, we analyze the spatial distribution patterns of 12 class B notifiable infectious diseases that remain active all over China. Methods: Global and local Moran’s I and corresponding graphic tools are adopted to explore and visualize the global and local spatial distribution of the incidence of the selected epidemics, respectively. Inter-correlations of clustering patterns of each pair of diseases and a cumulative summary of the high/low cluster frequency of the provincial units are also provided by means of figures and maps. Results: Of the 12 most commonly notifiable class B infectious diseases, viral hepatitis and tuberculosis show high incidence rates and account for more than half of the reported cases. Almost all the diseases, except pertussis, exhibit positive spatial autocorrelation at the provincial level. All diseases feature varying spatial concentrations. Nevertheless, associations exist between spatial distribution patterns, with some provincial units displaying the same type of cluster features for two or more infectious diseases. Overall, high–low (unit with high incidence surrounded by units with high incidence, the same below) and high–high spatial cluster areas tend to be prevalent in the provincial units located in western and southwest China, whereas low–low and low–high spatial cluster areas abound in provincial units in north and east China. Conclusion: Despite the various distribution patterns of 12 class B notifiable infectious diseases, certain similarities between their spatial distributions are present. Substantial evidence is available to support disease-specific, location-specific, and disease-combined interventions. Regarding provinces that show high–high/high–low patterns of multiple diseases, comprehensive interventions targeting different diseases should be established. As to the adjacent provincial units revealing similar patterns, coordinated actions need to be taken across borders. [ABSTRACT FROM AUTHOR]

Background: A large number of programs have been implemented in many countries to increase the healthcare workforce recruitment in rural and remote areas. Rural early exposure programs for medical students have been shown to be effective strategies. However, no related studies have been reported before in China. This study was carried out to determine the association between medical students’ participation in rural clinical clerkships and their intentions to choose rural medical work after graduation from western medical schools in China. Methods: Based on a two-stage random sampling method, the cross-sectional survey was carried out in ten western provinces in China. A brief questionnaire filled in by medical students was used for data collection. A total of 4278 medical students participated in the study. The response rate was approximately 90.34%. Pearson’s chi-squared tests and binary logistic regression analyses were performed for data analyses. Results: Approximately 52.0% of medical students disclosed intentions to work in rural medical institutions after graduation. Only one in five participants had experience with a rural clinical clerkship. Rural clinical clerkships were significantly associated with medical students’ intentions to work in rural medical institutions (OR: 1.24, 95%CI: 1.05–1.46); further analyses indicated that such clerkships only had a significant impact among the medical students with an urban background (OR: 2.10, 95%CI: 1.48–2.97). In terms of the sociodemographic characteristics, younger age, low level of parental education, majoring in general practice, and studying in low-level medical schools increased the odds of having intentions to engage in rural medical work among medical students; however, rural origins was the only positive univariate predictor. In addition, the predictors of intentions to choose rural medical work were different between medical students with a rural background and those with an urban background. Conclusions: Rural clinical clerkship is likely to increase the odds of having intentions to work in rural medical institutions after graduation among medical students in western China, especially for those with an urban background. Related policy makers could consider developing compulsory rural clerkship programs and implement them among medical students to increase early rural exposure. [ABSTRACT FROM AUTHOR]

Purpose: To assess a potential role of Bruch´s membrane (BM) in the biomechanics of the eye, we measured its thickness and the density of retinal pigment epithelium (RPE) cells in various ocular regions in eyes of varying axial length. Methods: Human globes, enucleated because of an ocular tumor or end-stage glaucoma were prepared for histological examination. Using light microscopy, the histological slides were histomorphometrically examined applying a digitized image analysis system. Results: The study included 104 eyes with a mean axial length of 27.9±3.2 mm (range:22.6mm-36.5mm). In eyes without congenital glaucoma, BM was significantly thickest (P<0.001) at the ora serrata, followed by the posterior pole, the midpoint between equator and posterior pole (MBEPP), and finally the equator. BM thickness was not significantly correlated with axial length (ora serrata: P = 0.93; equator:P = 0.31; MBEPP:P = 0.15; posterior pole:P = 0.35). RPE cell density in the pre-equatorial region (P = 0.02; regression coefficient r = -0.24) and in the retro-equatorial region (P = 0.03; r = -0.22) decreased with longer axial length, while RPE cell density at the ora serrata (P = 0.35), the MBEPP (P = 0.06; r = -0.19) and the posterior pole (P = 0.38) was not significantly correlated with axial length. Highly myopic eyes with congenital glaucoma showed a tendency towards lower BM thickness and lower RPE cell density at all locations. Conclusions: BM thickness, in contrast to scleral and choroidal thickness, was independent of axial length in eyes without congenital glaucoma. In association with an axial elongation associated decrease in the RPE cell density in the midperiphery, the findings support the notion of a biomechanical role BM may play in the process of emmetropization/myopization. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) characterized by loss of sensory sensitivity and pain in hands and feet is the major dose-limiting toxicity of many chemotherapeutics. At present, there are no FDA-approved treatments for CIPN. The anti-diabetic drug metformin is the most widely used prescription drug in the world and improves glycemic control in diabetes patients. There is some evidence that metformin enhances the efficacy of cancer treatment. The aim of this study was to test the hypothesis that metformin protects against chemotherapy-induced neuropathic pain and sensory deficits. Mice were treated with cisplatin together with metformin or saline. Cisplatin induced increased sensitivity to mechanical stimulation (mechanical allodynia) as measured using the von Frey test. Co-administration of metformin almost completely prevented the cisplatin-induced mechanical allodynia. Co-administration of metformin also prevented paclitaxel-induced mechanical allodynia. The capacity of the mice to detect an adhesive patch on their hind paw was used as a novel indicator of chemotherapy-induced sensory deficits. Co-administration of metformin prevented the cisplatin-induced increase in latency to detect the adhesive patch indicating that metformin prevents sensory deficits as well. Moreover, metformin prevented the reduction in density of intra-epidermal nerve fibers (IENFs) in the paw that develops as a result of cisplatin treatment. We conclude that metformin protects against pain and loss of tactile function in a mouse model of CIPN. The finding that metformin reduces loss of peripheral nerve endings indicates that mechanism underlying the beneficial effects of metformin includes a neuroprotective activity. Because metformin is widely used for treatment of type II diabetes, has a broad safety profile, and is currently being tested as an adjuvant drug in cancer treatment, clinical translation of these findings could be rapidly achieved. [ABSTRACT FROM AUTHOR]

Medulloblastoma (MB) is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT) or chemotherapy (CHT) is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE) tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS) rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT) and chemotherapy (CHT) were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT) was found significantly improving the survival of children (p<0.001) while it was not a significant prognostic factor for adult patients. Moreover, patients in WNT subtype had better OS (p = 0.028) than others (SHH and Non-SHH/WNT subtypes) given postoperative adjuvant therapies. Postoperative primary RT was found to be a strong prognostic factor influencing the survival in all histological and molecular subgroups (p<0.001). Postoperative primary CHT was found significantly to influence the survival of classic medulloblastoma (CMB) (OS p<0.001, EFS p<0.001), SHH subgroup (OS p = 0.020, EFS p = 0.049) and WNT subgroup (OS p = 0.003, EFS p = 0.016) but not in desmoplastic/nodular medulloblastoma (DMB) (OS p = 0.361, EFS p = 0.834) and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055). Our study showed postoperative primary CHT significantly influence the survival of CMB, SHH subgroup and WNT subgroup but not in DMB and Non-SHH/WNT subgroup of MB. [ABSTRACT FROM AUTHOR]

The miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) transcription factors function as an endogenous age cue in regulating plant phase transition and phase-dependent morphogenesis, but the control of SPL output remains poorly understood. In Arabidopsis thaliana the spatial pattern of trichome is a hallmark of phase transition and governed by SPLs. Here, by dissecting the regulatory network controlling trichome formation on stem, we show that the miR171-targeted LOST MERISTEMS 1 (LOM1), LOM2 and LOM3, encoding GRAS family members previously known to maintain meristem cell polarity, are involved in regulating the SPL activity. Reduced LOM abundance by overexpression of miR171 led to decreased trichome density on stems and floral organs, and conversely, constitutive expression of the miR171-resistant LOM (rLOM) genes promoted trichome production, indicating that LOMs enhance trichome initiation at reproductive stage. Genetic analysis demonstrated LOMs shaping trichome distribution is dependent on SPLs, which positively regulate trichome repressor genes TRICHOMELESS 1 (TCL1) and TRIPTYCHON (TRY). Physical interaction between the N-terminus of LOMs and SPLs underpins the repression of SPL activity. Importantly, other growth and developmental events, such as flowering, are also modulated by LOM-SPL interaction, indicating a broad effect of the LOM-SPL interplay. Furthermore, we provide evidence that MIR171 gene expression is regulated by its targeted LOMs, forming a homeostatic feedback loop. Our data uncover an antagonistic interplay between the two timing miRNAs in controlling plant growth, phase transition and morphogenesis through direct interaction of their targets. [ABSTRACT FROM AUTHOR]

The piRNA pathway plays an important role in maintaining genome stability in the germ line by silencing transposable elements (TEs) from fly to mammals. As a highly conserved piRNA pathway component, Piwi is widely expressed in both germ cells and somatic cells in the Drosophila ovary and is required for piRNA production in both cell types. In addition to its known role in somatic cap cells to maintain germline stem cells (GSCs), this study has demonstrated that Piwi has novel functions in somatic cells and germ cells of the Drosophila ovary to promote germ cell differentiation. Piwi knockdown in escort cells causes a reduction in escort cell (EC) number and accumulation of undifferentiated germ cells, some of which show active BMP signaling, indicating that Piwi is required to maintain ECs and promote germ cell differentiation. Simultaneous knockdown of dpp, encoding a BMP, in ECs can partially rescue the germ cell differentiation defect, indicating that Piwi is required in ECs to repress dpp. Consistent with its key role in piRNA production, TE transcripts increase significantly and DNA damage is also elevated in the piwi knockdown somatic cells. Germ cell-specific knockdown of piwi surprisingly causes depletion of germ cells before adulthood, suggesting that Piwi might control primordial germ cell maintenance or GSC establishment. Finally, Piwi inactivation in the germ line of the adult ovary leads to gradual GSC loss and germ cell differentiation defects, indicating the intrinsic role of Piwi in adult GSC maintenance and differentiation. This study has revealed new germline requirement of Piwi in controlling GSC maintenance and lineage differentiation as well as its new somatic function in promoting germ cell differentiation. Therefore, Piwi is required in multiple cell types to control GSC lineage development in the Drosophila ovary. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most malignant neoplasms originating in the digestive system. Focused ultrasound (FUS) treatment instead of the surgery operation has been used to treat Pancreatic cancer noninvasively in clinical trials. The endocrine and exocrine glands in pancreas provide the two unique functions for a person to be healthy. It is critically important to find out if the FUS treatment can still keep the normal functions of the two glands. The goal of this study is to examine and analyze changes in histopathology and serum glucose and amylase levels of the targeted in-vivo felines after the FUS treatment. Various percentage volumes of pancreas of felines were insonified. The FUS treatment (7.5 MHz of central frequency; 5 W of acoustical power; transducer f-number  = 0.33; 6 s insonification time per point) effectively generated coagulative necrosis at the insonified site while leaving tissue outside the insonified site intact. It was also observed that all felines endured well with the FUS treatment; changes introduced to pancreatic tissue after up to 50% of a pancreas by volume was insonified by the FUS procedure did not affect its normal endocrine and exocrine functions. [ABSTRACT FROM AUTHOR]

Background and Objective: Of three first-line anti-tuberculosis (anti-TB) drugs, isoniazid is most commonly associated with hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, NAT2, CYP2E1, GSTM1and GSTT1, that code for drug-metabolizing enzymes. This study evaluated whether the polymorphisms in these enzymes were associated with an increased risk of anti-TB drug-induced hepatitis in patients and could potentially be used to identify patients at risk of liver injury. Methods and Design: In a cross-sectional study, 2244 tuberculosis patients were assessed two months after the start of treatment. Anti-TB drug-induced liver injury (ATLI) was defined as an ALT, AST or bilirubin value more than twice the upper limit of normal. NAT2, CYP2E1, GSTM1 and GSTT1 genotypes were determined using the PCR/ligase detection reaction assays. Results: 2244 patients were evaluated, there were 89 cases of ATLI, a prevalence of 4% 9 patients (0.4%) had ALT levels more than 5 times the upper limit of normal. The prevalence of ATLI was greater among men than women, and there was a weak association with NAT2*5 genotypes, with ATLI more common among patients with the NAT2*5*CT genotype. The sensitivity of the CT genotype for identifying patients with ATLI was 42% and the positive predictive value 5.9%. CT ATLI was more common among slow acetylators (prevalence ratio 2.0 (95% CI 0.95,4.20) )compared to rapid acetylators. There was no evidence that ATLI was associated with CYP2E1 RsaIc1/c1genotype, CYP2E1 RsaIc1/c2 or c2/c2 genotypes, or GSTM1/GSTT1 null genotypes. Conclusions: In Xinjiang Uyghur TB patients, liver injury was associated with the genetic variant NAT2*5, however the genetic markers studied are unlikely to be useful for screening patients due to the low sensitivity and low positive predictive values for identifying persons at risk of liver injury. [ABSTRACT FROM AUTHOR]

Recurrence and progression to higher grade lesions are characteristic behaviorsof gliomas. Though IDH1 mutation frequently occurs and is considered as an early event in gliomagenesis, little is known about its role in the recurrence and progression of gliomas. We therefore analysed IDH1 and IDH2 statusat codon 132 of IDH1 and codon 172 of IDH2 by direct sequencing and anti-IDH1-R132H immunohistochemistry in 53 paired samples and their recurrences, including 29 low- grade gliomas, 16 anaplastic gliomas and 8 Glioblastomas. IDH1/IDH2 mutation was detected in 32 primarytumors, with 25 low- grade gliomas and 6 anaplastic gliomas harboring IDH1 mutation and 1 low- grade glioma harboring IDH2 mutation. All of the paired tumors showed consistent IDH1 and IDH2 status. Patients were analyzed according to IDH1 status and tumor-related factors. Malignant progression at recurrence was noted in 22 gliomas and was not associated with IDH1 mutation. Survival analysis revealed patients with IDH1 mutated gliomas had a significantly longer progression-free survival (PFS) and overall survival (OS). In conclusion, this study demonstrated a strong tendency of IDH1/IDH2 status being consistent during progression of glioma. IDH1 mutation was not a predictive marker for malignant progression and it was a potential prognostic marker for gliomas of Chinese patients. [ABSTRACT FROM AUTHOR]

MMPs comprise a family of proteolytic enzymes that degrade pericellular substances, which may result in the destabilization of vessels and related to the development of brain arteriovenous malformations (BAVM). MMP3 is a key member of this family, overexpressed in BAVM tissues, and a single nucleotide polymorphism within MMP3, −709A>G (rs522616), is significantly associated with the risk of BAVM. In this study, we aimed to investigate the mechanism through which the polymorphism rs522616 regulates the expression of MMP3. Our results showed that −709A led to a over 2-fold higher transcriptional activity compared with the G allele (P<0.05) and this transcriptional activity can be depressed by co-transfecting cells with competitive DNA fragments containing −709A but not −709G. Bioinformatics analyses suggested that the transcription factor C-MYB might bind to the area around rs522616. Overexpressed C-MYB significantly increased the transcriptional activity of −709A compared with −709G or controls that did not overexpress c-myb (P<0.01) in HEK293 and HUVEC cells. ChIP assays indicated that C-MYB bound to the SNP region in the two cell lines and three BAVM tissue samples. Together, these data indicated that C-MYB can bind to the −709A allele of the MMP3 promoter, activate its transcription and lead to a higher expression of this gene. This novel hypothesis, supported by molecular evidence, explains how this SNP affects MMP3 promoter function and results in a risk of BAVM development. [ABSTRACT FROM AUTHOR]

Background:The purpose of this study is to describe the prevalence of overweight, general obesity, and abdominal obesity and examine their associations with socioeconomic status in a rural Chinese adult population. Methods:This cross-sectional study was performed on 15,236 participants ≥ 35 years of age (6,313 men [41.4%] and 8,923 women [58.6%]). Each participant’s weight, height, waist circumference (WC), and hipline circumference (HC) were measured, and demographic and socioeconomic data were collected using questionnaires. Results:The mean body mass index (BMI) values were 23.31 ± 2.96 and 23.89 ± 3.23 kg m-2 and the mean WC values were 79.13 ± 8.43 and 79.54 ± 8.27 cm for men and women, respectively. The age-standardized prevalence rates of overweight (BMI ≥ 24.0 kg m-2), general obesity (BMI ≥ 28.0 kg m-2), and abdominal obesity (WC ≥ 85 cm for men and ≥ 80 cm for women) were 32.0%, 6.7%, and 27.0% for men and 35.1%, 9.7%, and 48.3% for women, respectively. All gender differences were statistically significant (p < 0.001). In addition, the age-specific prevalence rates of general and abdominal obesity slowly decreased among men but sharply increased among women as age increased (p < 0.001). In subsequent logistic regression analysis, educational level was negatively associated with both general obesity and abdominal obesity among women but positively associated with abdominal obesity among men. No significant correlation was found between obesity and income. Conclusions:These results suggest a high prevalence of obesity which might differ by gender and age, and an inverse association among women and a mixed association among men noted between education and obesity in our locality. Preventive and therapeutic programs are warranted to control this serious public health problem. The gender-specific characteristics of populations at high-risk of developing obesity should be taken into consideration when designing interventional programs. [ABSTRACT FROM AUTHOR]

Glioblastoma cells secrete extra-cellular vesicles (EVs) containing microRNAs (miRNAs). Analysis of these EV miRNAs in the bio-fluids of afflicted patients represents a potential platform for biomarker development. However, the analytic algorithm for quantitative assessment of EV miRNA remains under-developed. Here, we demonstrate that the reference transcripts commonly used for quantitative PCR (including GAPDH, 18S rRNA, and hsa-miR-103) were unreliable for assessing EV miRNA. In this context, we quantitated EV miRNA in absolute terms and normalized this value to the input EV number. Using this method, we examined the abundance of miR-21, a highly over-expressed miRNA in glioblastomas, in EVs. In a panel of glioblastoma cell lines, the cellular levels of miR-21 correlated with EV miR-21 levels (p<0.05), suggesting that glioblastoma cells actively secrete EVs containing miR-21. Consistent with this hypothesis, the CSF EV miR-21 levels of glioblastoma patients (n=13) were, on average, ten-fold higher than levels in EVs isolated from the CSF of non-oncologic patients (n=13, p<0.001). Notably, none of the glioblastoma CSF harbored EV miR-21 level below 0.25 copies per EV in this cohort. Using this cut-off value, we were able to prospectively distinguish CSF derived from glioblastoma and non-oncologic patients in an independent cohort of twenty-nine patients (Sensitivity=87%; Specificity=93%; AUC=0.91, p<0.01). Our results suggest that CSF EV miRNA analysis of miR-21 may serve as a platform for glioblastoma biomarker development. [ABSTRACT FROM AUTHOR]

The miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) transcription factors function as an endogenous age cue in regulating plant phase transition and phase-dependent morphogenesis, but the control of SPL output remains poorly understood. In Arabidopsis thaliana the spatial pattern of trichome is a hallmark of phase transition and governed by SPLs. Here, by dissecting the regulatory network controlling trichome formation on stem, we show that the miR171-targeted LOST MERISTEMS 1 (LOM1), LOM2 and LOM3, encoding GRAS family members previously known to maintain meristem cell polarity, are involved in regulating the SPL activity. Reduced LOM abundance by overexpression of miR171 led to decreased trichome density on stems and floral organs, and conversely, constitutive expression of the miR171-resistant LOM (rLOM) genes promoted trichome production, indicating that LOMs enhance trichome initiation at reproductive stage. Genetic analysis demonstrated LOMs shaping trichome distribution is dependent on SPLs, which positively regulate trichome repressor genes TRICHOMELESS 1 (TCL1) and TRIPTYCHON (TRY). Physical interaction between the N-terminus of LOMs and SPLs underpins the repression of SPL activity. Importantly, other growth and developmental events, such as flowering, are also modulated by LOM-SPL interaction, indicating a broad effect of the LOM-SPL interplay. Furthermore, we provide evidence that MIR171 gene expression is regulated by its targeted LOMs, forming a homeostatic feedback loop. Our data uncover an antagonistic interplay between the two timing miRNAs in controlling plant growth, phase transition and morphogenesis through direct interaction of their targets. [ABSTRACT FROM AUTHOR]