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Background: The leukemia affects not only the quality of life (QOL) of patients with the disease but also that of their family caregivers (FCs). The research studies on QOL of FCs for leukemia patients are limited. This study aimed to evaluate the QOL of FCs for leukemia patients in Heilongjiang province, China.Methods: A cross-sectional questionnaire survey was undertaken with 309 FCs for leukemia patients recruited from three hospitals in Heilongjiang province. The QOL of the participants was assessed using the Chinese version of WHOQOL-BREF. Multivariate regression models were established to determine the predictors of the QOL of FCs, including the socio-economic characteristics of patients and FCs, and the emotional distress, social support and family functions of FCs.Results: The FCs had low QOL scores in all four domains: 12.7 ± 2.8 for physical, 12.2 ± 2.5 for psychological, 13.2 ± 2.9 for social and 11.3 ± 2.5 for environment. Social support is a major predictor of the QOL of FCs, with a standardized β coefficient of "high support" ranging from 0.41 to 0.58 for the four domains, followed by family function (β = 0.37 ~ 0.44 for psychological, social and environmental domains). The FCs who were older, highly educated, had no religious belief, suffered from a higher level of emotional distress, and provided care to younger patients and the patients without insurance coverage had lower QOL than the others.Conclusion: The study provides some important insights into the QOL of FCs for leukemia patients. The QOL of FCs for leukemia patients is low and low levels of support to FCs are a major predictor of low QOL of FCs. [ABSTRACT FROM AUTHOR]

Background: Recently, a grayscale inversion view was reported to improve intra- and inter-observer reliabilities in measuring coronal curvature with Cobb and pedicle methods in scoliosis patients. However, the grayscale transformation has never been applied to the measurements of spinopelvic parameters. The purpose of this study was to compare the measurement reliabilities of the spinoplevic sagittal parameters between the 'Standard View' and the 'Grayscale Inversion View' in normal adult populations. Methods: A total of 30 asymptomatic subjects aged between 30 and 40 years were included in this study. Wholespine posteroanterior radiographs were used to measure the spinoplevic sagittal parameters including thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), sacral slope (SS) and pelvic tilt (PT) in both standard view and grayscale inversion view. Two independent observers measured the parameters twice at a 2-week interval. Intra- and inter-observer reliabilities were compared between the two radiographic views. The absolute differences between the two sets of measurements on each view were calculated and compared. Results: The intra-class correlation coefficients (ICCs) of PI, PT and SVA were greater in the grayscale inversion view than in the standard view (0.972 vs 0.817, 0.937 vs 0.833 and 0.964 vs 0.901 for observer 1, respectively; 0.990 vs 0. 826, 0.995 vs 0.842 and 0.969 vs 0.919 for observer 2, respectively). Overall, the improvement of ICC was greater in parameters of sagittal pelvic alignment than in those of sagittal spinal alignment. As for the mean absolute differences between two measurements, significant differences existed between the two views in terms of PI, PT and SVA (p = 0.014, 0.016 and 0.011 for observer 1, respectively; p = 0.014, 0.025 and 0.046 for observer 2, respectively). Conclusions: A grayscale inversion view provided improved intra- and inter-observer reliabilities in measuring spinoplevic alignment when compared with a standard view. This view was more useful in subjects whose pelvic anatomical structures can't be identified clearly on the standard X-ray view. [ABSTRACT FROM AUTHOR]

Background: Many researches have investigated the changes associated with immobilization-induced osteoarthritis (OA). However, there are only few studies focusing on the effect of unilateral knee immobilization on cartilage matrix changes in the contralateral mobile knee. The aim of the present study was to investigate the influence of immobilization on the cartilage matrix in the contralateral mobile knees in a rabbit model of OA induced by immobilization.Methods: Right knees (experimental knees) of eighteen mature female rabbits were immobilized at an extension of 180° with orthopedic casting tape for 2, 4, or 8 weeks. Left knees (contralateral knees) of the immobilized rabbits were not subjected to immobilization. The knees of six non-immobilized rabbits were designated as control knees. Following immobilization, cartilage specimens from the medial femoral condyle underwent macroscopic, histological, immunohistochemical, and biochemical evaluations.Results: Roughness of cartilage surface was detected in the experimental knees at 2 weeks, and cartilage degeneration was further developed. In the contralateral knee, cartilage showed degenerative changes after 4 weeks. Safranin-O staining and glycosaminoglycan (GAG) contents were reduced in the experimental knees following immobilization and in the contralateral intact knees after 4 and 8 weeks. Type II collagen staining was gradually reduced, type I collagen accumulation was obviously detected in the upper and middle layers of cartilage in experimental knees after 8 weeks, and the collagen orientation was gradually disorganized in both knees at 4 and 8 weeks. For both experimental and contralateral knees, collagen contents were significantly decreased at 8 weeks, and Mankin and Osteoarthritis Research Society International (OARSI) scores increased over time.Conclusion: OA developed in the contralateral intact knee with the progress of OA in the immobilized knee in a rabbit model of immobilization-induced OA. [ABSTRACT FROM AUTHOR]

Background: Metastasis is the major cause of cancer-related death. Forkhead Box M1 (FoxM1) is a master regulator of tumor metastasis. This study aims to identify new FoxM1 targets in regulating tumor metastasis using bioinformatics tools as well as biological experiments. Methods: Illumina microarray was used to profile WT and PTTG1 knockout HCT116 cells. R2 Genomics Analysis was used to identify PTTG1 as a potential FoxM1 targeted gene. Luciferase reporter array, EMSA and Chromatin Immunoprecipitation (ChIP) were used to determine the binding of FoxM1 to PTTG1 promoter. Boyden chamber assay was used to evaluate the effects of FoxM1-PTTG1 on cell migration and invasion. Splenic-injection induced liver metastasis model was used to evaluate the effects of FoxM1-PTTG1 on liver metastasis of colorectal cancer. Results: Analyses of multiple microarray datasets derived from human colorectal cancer indicated that correlation levels of FoxM1 and pituitary tumor transforming gene (PTTG1) are highly concordant (R = 0.68 ~ 0.89, p = 2.1E-226 ~ 9.6E-86). FoxM1 over-expression increased and knock-down decreased PTTG1 expression. Luciferase reporter assay identified that the -600 to -300 bp region of PTTG1 promoter is important for FoxM1 to enhance PTTG1 promoter activity. EMSA and ChIP assays confirmed that FoxM1 directly binds to PTTG1 promoter at the -391 to -385 bp region in colorectal cancer cells. Boyden chamber assay indicated that both FoxM1 and PTTG1 regulate migration and invasion of HCT116 and SW620 colorectal cancer cells. Further in vivo assays indicated that PTTG1 knock out decreased the liver metastasis of FoxM1 over-expressing HCT116 cells. Microarray analyses identified 662 genes (FDR < 0.05) differentially expressed between WT and PTTG1-/- HCT116 cells. Among them, dickkopf homolog 1 (DKK1), a known WNT pathway inhibitor, was suppressed by PTTG1 and FoxM1. Conclusions: PTTG1 is a FoxM1 targeted gene. FoxM1 binds to PTTG1 promoter to enhance PTTG1 transcription, and FoxM1-PTTG1 pathway promotes colorectal cancer migration and invasion. [ABSTRACT FROM AUTHOR]

Salmonella arizonae (also called Salmonella subgroup IIIa) is a Gram-negative, non-spore-forming, motile, rod-shaped, facultatively anaerobic bacterium. S. arizonae strain RKS2983 was isolated from a human in California, USA. S. arizonae lies somewhere between Salmonella subgroups I (human pathogens) and V (also called S. bongori; usually non-pathogenic to humans) and so is an ideal model organism for studies of bacterial evolution from non-human pathogen to human pathogens. We hence sequenced the genome of RKS2983 for clues of genomic events that might have led to the divergence and speciation of Salmonella into distinct lineages with diverse host ranges and pathogenic features. The 4,574,836 bp complete genome contains 4,203 protein-coding genes, 82 tRNA genes and 7 rRNA operons. This genome contains several characteristics not reported to date in Salmonella subgroup I or V and may provide information about the genetic divergence of Salmonella pathogens. [ABSTRACT FROM AUTHOR]

Background: Adenocarcinoma of the urinary bladder is a rare malignancy. Radical surgery is suggested as the best available treatment for early-stage disease, but there is currently no consensus on standard chemotherapy regimen for advanced stage. We assessed the feasibility and effect of neoadjuvant chemotherapy with gemcitabine and cisplatin (GC) plus S-1 for patients with locally advanced primary adenocarcinomas of the urinary bladder. Methods: Six patients with locally advanced urachal or non-urachal (n = 3, each) primary adenocarcinoma of the bladder were treated from October 2010 to October 2013 at a single center. All the patients were treated with 3 cycles (21d, each) of GC plus S-1 (gemcitabine, 1000 mg/m², days 1 and 8; cisplatin, 70 mg/m², day 2; and S-1, 50 mg bid, day 1-14). After neoadjuvant chemotherapy, patients with urachal cancer were treated with en bloc radical cystectomy and umbilectomy; the remaining 3 patients were treated with cystectomy. Results: All patients successfully completed the neoadjuvant chemotherapy without serious side effects. Two patients were assessed as complete response, 2 as partial response, 1 as stable disease and 1 as progressive disease. Conclusions: Despite the limitations of a small study population, the GC plus S-1 regimen for locally advanced primary adenocarcinoma of the urinary bladder was effective, and facilitated the success of surgery to a certain extent. Short follow-up time was also a limitation of our study. More studies are needed to evaluate the results. [ABSTRACT FROM AUTHOR]

Background: Haemonchus contortus is a common bloodsucking nematode causing widespread economic loss in agriculture. Upon H. contortus infection, a series of host responses is elicited, especially those related to T lymphocyte immunity. Existing studies mainly focus on the general immune responses of sheep T lymphocyte to H. contortus, lacking investigations at the molecular level. The objective of this study was to obtain a systematic transcriptional profiling of the T lymphocytes in H. contortus primary-infected sheep. Methods: Nematode-free sheep were orally infected once with H. contortus L3s. T lymphocyte samples were collected from the peripheral blood of 0, 3, 30 and 60 days post infection (dpi) infected sheep. Microarrays were used to compare gene transcription levels between samples. Quantitative RT-PCR was employed to validate the microarray data. Gene Ontology and KEGG pathway analysis were utilized for the annotation of differentially expressed genes. Results: Our microarray data was consistent with qPCR results. From microarrays, 853, 242 and 42 differentially expressed genes were obtained in the 3d vs. 0d, 30d vs. 0d and 60d vs. 0d comparison groups, respectively. Gene Ontology and KEGG pathway analysis indicated that these genes were involved in metabolism, signaling, cell growth and immune system processes. Functional analysis of significant differentially expressed genes, such as SLC9A3R2, ABCB9, COMMD4, SUGT1, FCER1G, GSK3A, PAK4 and FCER2, revealed a crucial association with cellular homeostasis maintenance and immune response. Our data suggested that maintaining both effective immunological response and natural cellular activity are important for T lymphocytes in fighting against H. contortus infection. Conclusions: Our results provide a substantial list of candidate genes in sheep T lymphocytes response to H. contortus infection, and contribute novel insights into a general immune response upon infection. [ABSTRACT FROM AUTHOR]

Background: A large number of single nucleotide polymorphisms (SNPs) associated with cervical cancer have been identified through candidate gene association studies and genome-wide association studies (GWAs). However, some studies have yielded different results for the same SNP. To obtain a more comprehensive understanding, we performed a meta-analysis on previously published case–control studies involving the SNPs associated with cervical cancer. Methods: Electronic searches of PubMed and Embase were conducted for all publications about the association between gene polymorphisms and cervical cancer. One-hundred and sixty-seven association studies were included in our research. For each SNP, three models (the allele, dominant and recessive effect models) were adopted in the meta-analysis. For each model, the effect summary odds ratio (OR) and 95% CI were calculated. Heterogeneity between studies was evaluated by Cochran’s Q test. If the p value of Q test was less than 0.01, a random effect model was used; otherwise, a fixed effect model was used. Results: The results of our meta-analysis showed that: (1) There were 8, 2 and 8 SNPs that were significantly associated with cervical cancer (P < 0.01) in the allele, dominant and recessive effect models, respectively. (2) rs1048943 (CYP1A1 A4889G) showed the strongest association with cervical cancer in the allele effect model (1.83[1.57, 2.13]); in addition, rs1048943 (CYP1A1 A4889G) had a very strong association in the dominant and recessive effect model. (3) 15, 11 and 10 SNPs had high heterogeneity (P < 0.01) in the three models, respectively. (4) There was no published bias for most of the SNPs according to Egger’s test (P < 0.01) and Funnel plot analysis. For some SNPs, their association with cervical cancer was only tested in a few studies and, therefore, might have been subjected to published bias. More studies on these loci are required. Conclusion: Our meta-analysis provides a comprehensive evaluation of cervical cancer association studies. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis explored the efficacy and safety of anterior cervical corpectomy and fusion (ACCF) comparing to anterior cervical discectomy and fusion (ACDF) in treating cervical spondylotic myelopathy (CSM) patients. Methods: Several electronic databases were searched combined with manually searching. Thirteen randomized controlled studies were enrolled with 1,062 CSM patients, including 468 patients and 594 patients in the in the ACCF and ACDF group, respectively. The meta-analysis was then performed using the STATA 12.0 software. Crude standard mean difference (SMD) or odds ratio (OR) with their 95% confidence intervals (CI) were calculated. Results: Our meta-analysis results revealed that CSM patients in ACDF group showed less blood loss than those in ACCF group (SMD = 1.21, 95% CI = 1.03 ~ 1.39, P < 0.001). The operation time of CSM patients in the ACDF group was also obviously shorter than those in ACCF group (SMD = 0.40, 95% CI = 0.23 ~ 0.57, P < 0.001). Furthermore, CSM patients in ACDF group had shorter hospital time than those in ACCF group (SMD = 0.45, 95% CI = 0.21 ~ 0.69, P < 0.001). Conclusion: Our findings provide empirical evidence that ACDF may be more effective than ACCF for CSM treatment. [ABSTRACT FROM AUTHOR]

Objectives Several preference-based health-related quality of life (HRQoL) instruments have been published and widely used in different populations. However no consensus has emerged regarding the most appropriate instrument in therapeutic area of stable angina. This study compared and validated the psychometric properties of two generic preference-based instruments, the EQ-5D and SF-6D, among Chinese stable angina patients. Methods Convergent validity of the EQ-5D and SF-6D was examined with eight a priori hypotheses from stable angina patients in conjunction with Seattle Angina Questionnaire (SAQ). Responsiveness was compared using the effect size (ES), relative efficiency (RE) and receiver operating characteristic (ROC) curves. Agreement between the EQ-5D and SF-6D was tested using intra-class correlation coefficient (ICC) and Bland-Altman plot. Factors affecting utility difference were explored with multiple linear regression analysis. Results In 411 patients (mean age 68.08 ± 11.35), mean utility scores (SD) were 0.78 (0.15) for the EQ-5D and 0.68 (0.12) for the SF-6D. Validity was demonstrated by the moderate to strong correlation coefficients (Range: 0.368-0.594, P< 0.001) for five of the eight hypotheses in both the EQ-5D and SF-6D. There were no serious floor effects for the EQ-5D and SF-6D, but ceiling effects for the EQ-5D were large. The areas under ROC of them all exceeded 0.5 (0.660-0.814, P< 0.001). The SF-6D showed a better discriminative capacity (ES: 0.573 to 1.179) between groups with different stable-angina-specific health status than the EQ-5D (ES: 0.426 to 1.126). RE suggested that the SF-6D (RE: 44.8 to 177.8%) was more efficient than the EQ-5D except for physical function. Poor agreement between them was observed with ICC (0.448, P< 0.001) and Bland-Altman plot analysis. Multiple liner regression showed that clinical variables significantly (P< 0.05) influenced differences in utility scores between the EQ-5D and SF-6D. Conclusions Both EQ-5D and SF-6D are valid and sensitive preference-based HRQoL instruments in Chinese stable angina patients. The SF-6D may be a more effective tool with lower ceiling effect and greater sensitivity. Further study is needed to compare other properties, such as reliability and longitudinal response. [ABSTRACT FROM AUTHOR]

Background Since the global standards for postgraduate medical education (PGME) were published in January 2003, they have gained worldwide attention. The current state of residency training programs in medical-school-affiliated hospitals throughout China was assessed in this study. Methods Based on the internationally recognized global standards for PGME, residents undergoing residency training at that time and the relevant residency training instructors and management personnel from 15 medical-school-affiliated hospitals throughout China were recruited and surveyed regarding the current state of residency training programs. A total of 938 questionnaire surveys were distributed between June 30, 2006 and July 30, 2006; of 892 surveys collected, 841 were valid. Results For six items, the total proportions of "basically meets standards" and "completely meets standards" were <70% for the basic standards. These items were identified in the fields of "training settings and educational resources", "evaluation of training process", and "trainees". In all fields other than "continuous updates", the average scores of the western regions were significantly lower than those of the eastern regions for both the basic and target standards. Specifically, the average scores for the basic standards on as many as 25 of the 38 items in the nine fields were significantly lower in the western regions. There were significant differences in the basic standards scores on 13 of the 38 items among trainees, instructors, and managers. Conclusions The residency training programs have achieved satisfactory outcomes in the hospitals affiliated with various medical schools in China. However, overall, the programs remain inadequate in certain areas. For the governments, organizations, and institutions responsible for PGME, such global standards for PGME are a very useful self-assessment tool and can help identify problems, promote reform, and ultimately standardize PGME. [ABSTRACT FROM AUTHOR]

Background: Cancer cell differentiation is an important characteristic of malignant tumor and has a great impact on prognosis and therapeutic decision for patients. The N-myc downstream regulated gene 1 (NDRG1), a putative tumor suppression gene, is involved in the regulation of human cell differentiation and metastasis in various cancers. Changes in the status of methylation of the NDRG1 gene have not been studied in detail in human breast cancer. Results: The MDA-MB-231 breast tumor cell line could express NDRG1. However, it was only expressed after treatment with 5-Aza-2'-deoxycytidine (AZA) in T47D cell line, which revealed that NDRG1 expression could modulated by DNA methylation. Therefore, the fragment surrounding the transcript start site of NDRG1 gene promoter was cloned after sodium bisulfite DNA treatment. A high density (66%) of methylation for human NDRG1 gene promoter was detected in T47D; however, there was only 16% of methylated CpG dinucleotides in the NDRG1 gene promoter in MDA-MB-231. DNA methylation in the NDRG1 promoter was detected in 31.1% of primary breast cancer samples. Furthermore, the NDRG1 promoter methylation correlated with the Tumor Node Metastasis (TNM) at stage III/IV, metastasis, lymph invasion, moderate and poor histological grade in the breast cancer patients. Conclusion: These findings suggest that the DNA methylation status of NDRG1 gene may play an important role in the pathogenesis and/or development of breast cancer, and the expression could be regulated by aberrant DNA methylation. [ABSTRACT FROM AUTHOR]

Background: Clinically, Charcot-Marie-Tooth disease (CMT)-associated muscle atrophy still lacks effective treatment. Deletion and mutation of L-periaxin can be involved in CMT type 4F (CMT4F) by destroying the myelin sheath form, which may be related to the inhibitory role of Ezrin in the self-association of L-periaxin. However, it is still unknown whether L-periaxin and Ezrin are independently or interactively involved in the process of muscle atrophy by affecting the function of muscle satellite cells., Method: A gastrocnemius muscle atrophy model was prepared to mimic CMT4F and its associated muscle atrophy by mechanical clamping of the peroneal nerve. Differentiating C2C12 myoblast cells were treated with adenovirus-mediated overexpression or knockdown of Ezrin. Then, overexpression of L-periaxin and NFATc1/c2 or knockdown of L-periaxin and NFATc3/c4 mediated by adenovirus vectors were used to confirm their role in Ezrin-mediated myoblast differentiation, myotube formation and gastrocnemius muscle repair in a peroneal nerve injury model. RNA-seq, real-time PCR, immunofluorescence staining and Western blot were used in the above observation., Results: For the first time, instantaneous L-periaxin expression was highest on the 6th day, while Ezrin expression peaked on the 4th day during myoblast differentiation/fusion in vitro. In vivo transduction of adenovirus vectors carrying Ezrin, but not Periaxin, into the gastrocnemius muscle in a peroneal nerve injury model increased the numbers of muscle myosin heavy chain (MyHC) I and II type myofibers, reducing muscle atrophy and fibrosis. Local muscle injection of overexpressed Ezrin combined with incubation of knockdown L-periaxin within the injured peroneal nerve or injection of knockdown L-periaxin into peroneal nerve-injured gastrocnemius muscle not only increased the number of muscle fibers but also recovered their size to a relatively normal level in vivo. Overexpression of Ezrin promoted myoblast differentiation/fusion, inducing increased MyHC-I + and MyHC-II + muscle fiber specialization, and the specific effects could be enhanced by the addition of adenovirus vectors for knockdown of L-periaxin by shRNA. Overexpression of L-periaxin did not alter the inhibitory effects on myoblast differentiation and fusion mediated by knockdown of Ezrin by shRNA in vitro but decreased myotube length and size. Mechanistically, overexpressing Ezrin did not alter protein kinase A gamma catalytic subunit (PKA-γ cat), protein kinase A I alpha regulatory subunit (PKA reg Iα) or PKA reg Iβ levels but increased PKA-α cat and PKA reg II α levels, leading to a decreased ratio of PKA reg I/II. The PKA inhibitor H-89 remarkably abolished the effects of overexpressing-Ezrin on increased myoblast differentiation/fusion. In contrast, knockdown of Ezrin by shRNA significantly delayed myoblast differentiation/fusion accompanied by an increased PKA reg I/II ratio, and the inhibitory effects could be eliminated by the PKA reg activator N6-Bz-cAMP. Meanwhile, overexpressing Ezrin enhanced type I muscle fiber specialization, accompanied by an increase in NFATc2/c3 levels and a decrease in NFATc1 levels. Furthermore, overexpressing NFATc2 or knocking down NFATc3 reversed the inhibitory effects of Ezrin knockdown on myoblast differentiation/fusion., Conclusions: The spatiotemporal pattern of Ezrin/Periaxin expression was involved in the control of myoblast differentiation/fusion, myotube length and size, and myofiber specialization, which was related to the activated PKA-NFAT-MEF2C signaling pathway, providing a novel L-Periaxin/Ezrin joint strategy for the treatment of muscle atrophy induced by nerve injury, especially in CMT4F., (© 2023. The Author(s).)

Background: Tuberculosis (TB) and Acquired Immune Deficiency Syndrome (AIDS) are leading causes of death globally. However, little is known about the long-term mortality risk and the timeline of death in those co-infected with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (MTB). This study sought to understand the long-term mortality risk, factors, and the timeline of death in those with HIV-Mycobacterium tuberculosis (MTB) coinfection, particularly in those with insufficient TB treatment., Methods: TB-cause specific deaths were classified using a modified 'Coding of Cause of Death in HIV' protocol. A longitudinal cross-registration-system checking approach was used to confirm HIV/MTB co-infection between two observational cohorts. Mortality from the end of TB treatment (6 months) to post-treatment year (PTY) 5 (60 months) was investigated by different TB treatment outcomes. General linear models were used to estimate the mean mortality at each time-point and change between time-points. Cox's proportional hazard regressions measured the mortality hazard risk (HR) at each time-point. The Mantel-Haenszel stratification was used to identify mortality risk factors. Mortality density was calculated by person year of follow-up., Results: At the end point, mortality among patients with HIV/MTB coinfection was 34.7%. From the end of TB treatment to PTY5, mortality and loss of person years among individuals with TB treatment failure, missing, and adverse events (TBFMA) were significantly higher than those who had TB cure (TBC) and TB complete regimen (TBCR). Compared to individuals with TBC and with TBCR, individuals with TBFMA tended to die earlier and their mortality was significantly higher (HR TBFMA-TBC  = 3.0, 95% confidence interval: 2.5-3.6, HR TBFMA-TBCR  = 2.9, 95% CI: 2.5-3.4, P < 0.0001). Those who were naïve to antiretroviral therapy, were farmers, had lower CD4 counts (≤200 cells/μL) and were ≥ 50 years of age were at the highest risk of mortality. Mortality risk for participants with TBFMA was significantly higher across all stratifications except those with a CD4 count of ≤200 cells/μL., Conclusions: Earlier and long-term mortality among those with HIV/MTB co-infection is a significant problem when TB treatment fails or is inadequate.