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Despite rapid advances in metabolic therapies over the past decade, their efficacy in melanoma has been modest, largely due to the interaction between cancer-associated fibroblasts (CAFs) and cancer cells to promote cancer growth. Altering the tumor microenvironment (TME) is challenging and elusive. CAFs is critical for glutamine deprivation survival in melanoma. In this research, we assembled a CAFs-targeted, controlled-release nanodroplets for the combined delivery of the amino acid transporter ASCT2 (SLC1A5) inhibitor V9302 and GLULsiRNA (siGLUL). The application of ultrasound-targeted microbubble disruption (UTMD) allows for rapid release of V9302 and siGLUL, jointly breaking the glutamine metabolism interaction between CAFs and cancer cells on one hand, on the other hand, blocking activated CAFs and reducing the expression of extracellular matrix (ECM) to facilitate drug penetration. In addition, ultrasound stimulation made siGLUL more accessible to tumor cells and CAFs, downregulating GLUL expression in both cell types. FH-V9302-siGLUL-NDs also serve as contrast-enhanced ultrasound imaging agents for tumor imaging. Our study developed and reported FH-NDs as nanocarriers for V9302 and siGLUL, demonstrating that FH-V9302-siGLUL-NDs have potential bright future applications for integrated diagnostic therapy. Graphical Abstract [ABSTRACT FROM AUTHOR]

Background: Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) is a cancer stem cell marker, and its expression correlates with prognosis in a number of malignancies. The aim of this study is to determine the relationship of ALDH1A1 expression with clinicopathological parameters and prognosis in gastric cancer. Methods: ALDH1A1 and matrix metallopeptidase 9 (MMP-9) was evaluated by immunohistochemistry in 216 gastric carcinoma samples. The association between expression of ALDH1A1 and MMP-9, clinicopathological parameters, and prognosis of gastric cancer was examined. Results: ALDH1A1 protein expression was significantly associated with depth invasion, lymph node metastasis and stage of disease (all P < 0.05). Both univariate and multivariate analyses revealed that ALDH1A1 was an independent prognostic factor for both overall survival (OS) and recurrence-free survival (RFS) (both P < 0.001). Furthermore, ALDH1A1 overexpression was associated with poor prognosis in patients subgroups stratified by tumor size, depth invasion and lymph node metastasis. Moreover, ALDH1A1 was significantly correlated with MMP-9 among 216 gastric cancer tissues (P < 0.001). Patients who had ALDH1A1 overexpression, in which tumor cells displayed high invasiveness, had poor OS and shorter RFS. Conclusion: ALDH1A1 plays an important role in tumor aggressiveness and prognosis, and may act as a promising target for prognostic prediction. [ABSTRACT FROM AUTHOR]

Pyroptosis, a novel type of programmed cell death (PCD), which provides a feasible therapeutic option for the treatment of tumors. However, due to the hypermethylation of the promoter, the critical protein Gasdermin E (GSDME) is lacking in the majority of cancer cells, which cannot start the pyroptosis process and leads to dissatisfactory therapeutic effects. Additionally, the quick clearance, systemic side effects, and low concentration at the tumor site of conventional pyroptosis reagents restrict their use in clinical cancer therapy. Here, we described a combination therapy that induces tumor cell pyroptosis via the use of ultrasound-targeted microbubble destruction (UTMD) in combination with DNA demethylation. The combined application of UTMD and hydralazine-loaded nanodroplets (HYD-NDs) can lead to the rapid release of HYD (a demethylation drug), which can cause the up-regulation of GSDME expression, and produce reactive oxygen species (ROS) by UTMD to cleave up-regulated GSDME, thereby inducing pyroptosis. HYD-NDs combined with ultrasound (US) group had the strongest tumor inhibition effect, and the tumor inhibition rate was 87.15% (HYD-NDs group: 51.41 ± 3.61%, NDs + US group: 32.73%±7.72%), indicating that the strategy had a more significant synergistic anti-tumor effect. In addition, as a new drug delivery carrier, HYD-NDs have great biosafety, tumor targeting, and ultrasound imaging performance. According to the results, the combined therapy reasonably regulated the process of tumor cell pyroptosis, which offered a new strategy for optimizing the therapy of GSDME-silenced solid tumors. [ABSTRACT FROM AUTHOR]

Inflammatory myofibroblastic tumors (IMTs) of the heart are rarely observed in the eldly. We report a case involving an elderly woman with an IMT situated on the right atrial wall. The tumor was fully excised. The patient had a smooth recovery post-surgery and remained free of recurrence for three years. [ABSTRACT FROM AUTHOR]

Background: More efficient instruments for body constitution identification are needed for clinical practice. We aimed to develop the short-form version of the Constitution in Chinese Medicine Questionnaire (CCMQ) and evaluate for health management. Methods: First, the short forms were developed through expert survey, classical test theory (CTT), and modern item response (IRT) based on the CCMQ. A combination of e-mail and manual methods was used in expert survey. Then, five indexes of CTT including criteria value-critical ratio, correlation coefficient, discrete tendency, internal consistency, and factor loading were used. And, IRT method was used through analyzing the discrimination and difficulty parameters of items. Second, the three top-ranked items of each constitution scale were selected for the simplified CCMQ, based on the three combined methods of different conditions and weights. Third, The psychometric properties such as completion time, validity (Construct, criterion, and divergent validity), and reliability (test–retest and internal consistency reliability) were evaluated. Finally, the diagnostic validity of the best short-form used receiver operating characteristic (ROC) curve. Results: Three short-form editions were developed, and retained items 27, 23 and 27, which are named as WangQi nine body constitution questionnaire of Traditional Chinese Medicine (short-form) (SF-WQ9CCMQ)- A, B, and C, respectively. SF-WQ9CCMQ- A is showed the best psychometric property on Construct validity, Criterion validity, test–retest reliability and internal consistency reliability. The diagnostic validity indicated that the area under the ROC curve was 0.928 (95%CI: 0.924–0.932) for the Gentleness constitution scale, and were 0.895–0.969 and 0.911–0.981 for unbalance constitution scales using the cut-off value of the original CCMQ as 40 ("yes" standard) and 30 ("tendency" standard), respectively. Conclusions: Our study successfully developed a well short-form which has good psychometric property, and excellent diagnostic validity consistent with the original. New and simplified instrument and opportunity are provided for body constitution identification, health management and primary care implementation. [ABSTRACT FROM AUTHOR]

Objective: The accurate preoperative differentiation of benign and malignant adnexal masses, especially those with complex ultrasound morphology, remains a great challenge for junior sonographers. The purpose of this study was to develop and validate a nomogram based on the Ovarian-Adnexal Reporting and Data System (O-RADS) for predicting the malignancy risk of adnexal masses with complex ultrasound morphology. Methods: A total of 243 patients with data on adnexal masses with complex ultrasound morphology from January 2019 to December 2020 were selected to establish the training cohort, while 106 patients with data from January 2021 to December 2021 served as the validation cohort. Univariate and multivariate analyses were used to determine independent risk factors for malignant tumors in the training cohort. Subsequently, a predictive nomogram model was developed and validated in the validation cohort. The calibration, discrimination, and clinical net benefit of the nomogram model were assessed separately by calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Finally, we compared this model to the O-RADS. Results: The O-RADS category, an elevated CA125 level, acoustic shadowing and a papillary projection with color Doppler flow were the independent predictors and were incorporated into the nomogram model. The area under the ROC curve (AUC) of the nomogram model was 0.958 (95% CI, 0.932–0.984) in the training cohort. The specificity and sensitivity were 0.939 and 0.893, respectively. This nomogram also showed good discrimination in the validation cohort (AUC = 0.940, 95% CI, 0.899–0.981), with a sensitivity of 0.915 and specificity of 0.797. In addition, the nomogram model showed good calibration efficiency in both the training and validation cohorts. DCA indicated that the nomogram was clinically useful. Furthermore, the nomogram model had higher AUC and net benefit than the O-RADS. Conclusion: The nomogram based on the O-RADS showed a good predictive ability for the malignancy risk of adnexal masses with complex ultrasound morphology and could provide help for junior sonographers. [ABSTRACT FROM AUTHOR]

Immunotherapy had demonstrated inspiring effects in tumor treatment, but only a minority of people could benefit owing to the hypoxic and immune-suppressed tumor microenvironment (TME). Therefore, there was an urgent need for a strategy that could relieve hypoxia and increase infiltration of tumor lymphocytes simultaneously. In this study, a novel acidity-responsive nanoscale ultrasound contrast agent (L-Arg@PTX nanodroplets) was constructed to co-deliver paclitaxel (PTX) and L-arginine (L-Arg) using the homogenization/emulsification method. The L-Arg@PTX nanodroplets with uniform size of about 300 nm and high drug loading efficiency displayed good ultrasound diagnostic imaging capability, improved tumor aggregation and achieved ultrasound-triggered drug release, which could prevent the premature leakage of drugs and thus improve biosafety. More critically, L-Arg@PTX nanodroplets in combination with ultrasound targeted microbubble destruction (UTMD) could increase cellular reactive oxygen species (ROS), which exerted an oxidizing effect that converted L-Arg into nitric oxide (NO), thus alleviating hypoxia, sensitizing chemotherapy and increasing the CD8 + cytotoxic T lymphocytes (CTLs) infiltration. Combined with the chemotherapeutic drug PTX-induced immunogenic cell death (ICD), this promising strategy could enhance immunotherapy synergistically and realize powerful tumor treatment effect. Taken together, L-Arg@PTX nanodroplets was a very hopeful vehicle that integrated drug delivery, diagnostic imaging, and chemoimmunotherapy. [ABSTRACT FROM AUTHOR]

Background: Cassava (Manihot esculenta Crantz) is a major crop extensively cultivated in the tropics as both an important source of calories and a promising source for biofuel production. Although stable gene expression have been used for transgenic breeding and gene function study, a quick, easy and large-scale transformation platform has been in urgent need for gene functional characterization, especially after the cassava full genome was sequenced. Methods: Fully expanded leaves from in vitro plantlets of Manihot esculenta were used to optimize the concentrations of cellulase R-10 and macerozyme R-10 for obtaining protoplasts with the highest yield and viability. Then, the optimum conditions (PEG4000 concentration and transfection time) were determined for cassava protoplast transient gene expression. In addition, the reliability of the established protocol was confirmed for subcellular protein localization. Results: In this work we optimized the main influencing factors and developed an efficient mesophyll protoplast isolation and PEG-mediated transient gene expression in cassava. The suitable enzyme digestion system was established with the combination of 1.6% cellulase R-10 and 0.8% macerozyme R-10 for 16 h of digestion in the dark at 25 °C, resulting in the high yield (4.4 × 107 protoplasts/g FW) and vitality (92.6%) of mesophyll protoplasts. The maximum transfection efficiency (70.8%) was obtained with the incubation of the protoplasts/vector DNA mixture with 25% PEG4000 for 10 min. We validated the applicability of the system for studying the subcellular localization of MeSTP7 (an H+/monosaccharide cotransporter) with our transient expression protocol and a heterologous Arabidopsis transient gene expression system. Conclusion: We optimized the main influencing factors and developed an efficient mesophyll protoplast isolation and transient gene expression in cassava, which will facilitate large-scale characterization of genes and pathways in cassava. [ABSTRACT FROM AUTHOR]

Background: Preserved ratio impaired spirometry (PRISm) refers to decreased forced expiratory volume in 1 s (FEV1) in the setting of preserved ratio. Little is known about the role of PRISm and its complex relation with small airway dysfunction (SAD) and lung volume. Therefore, we aimed to investigate the associations between PRISm and SAD and lung volume.Methods: We conducted a cross-sectional community-dwelling study in China. Demographic data, standard respiratory epidemiology questionnaire, spirometry, impulse oscillometry (IOS) and computed tomography (CT) data were collected. PRISm was defined as post-bronchodilator FEV1/FVC ≥ 0.70 and FEV1 < 80% predicted. Spirometry-defined SAD was defined as at least two of three of the post-bronchodilator maximal mid-expiratory flow (MMEF), forced expiratory flow 50% (FEF50), and forced expiratory flow 75% (FEF75) less than 65% of predicted. IOS-defined SAD and CT-defined gas trapping were defined by the fact that the cutoff value of peripheral airway resistance R5-R20 > 0.07 kPa/L/s and LAA- 856>20%, respectively. Analysis of covariance and logistic regression were used to determine associations between PRISm and SAD and lung volume. We then repeated the analysis with a lower limit of normal definition of spirometry criteria and FVC definition of PRISm. Moreover, we also performed subgroup analyses in ever smoker, never smoker, subjects without airway reversibility or self-reported diagnosed asthma, and subjects with CT-measured total lung capacity ≥70% of predicted.Results: The final analysis included 1439 subjects. PRISm had higher odds and more severity in spirometry-defined SAD (pre-bronchodilator: odds ratio [OR]: 5.99, 95% confidence interval [95%CI]: 3.87-9.27, P < 0.001; post-bronchodilator: OR: 14.05, 95%CI: 8.88-22.24, P < 0.001), IOS-defined SAD (OR: 2.89, 95%CI: 1.82-4.58, P < 0.001), and CT-air trapping (OR: 2.01, 95%CI: 1.08-3.72, P = 0.027) compared with healthy control after adjustment for confounding factors. CT-measured total lung capacity in PRISm was lower than that in healthy controls (4.15 ± 0.98 vs. 4.78 ± 1.05 L, P < 0.05), after adjustment. These results were robust in repeating analyses and subgroup analyses.Conclusion: Our finding revealed that PRISm was associated with SAD and reduced total lung capacity. Future studies to identify the underlying mechanisms and longitudinal progression of PRISm are warranted. [ABSTRACT FROM AUTHOR]

Background: Aging has been evidenced to bring about some structural and functional lung changes, especially in COPD. However, whether aging affects SAD, a possible precursor of COPD, has not been well characterized.Objective: We aimed to comprehensively assess the relationship between aging and SAD from computed tomography, impulse oscillometry, and spirometry perspectives in Chinese.Methods: We included 1859 participants from ECOPD, and used a linear-by-linear association test for evaluating the prevalence of SAD across various age subgroups, and multivariate regression models for determining the impact of age on the risk and severity of SAD. We then repeated the analyses in these subjects stratified by airflow limitation.Results: The prevalence of SAD increases over aging regardless of definitional methods. After adjustment for other confounding factors, per 10-yrs increase in age was significantly associated with the risk of CT-defined SAD (OR 2.57, 95% CI 2.13 to 3.10) and the increase in the severity of air trapping (β 2.09, 95% CI - 0.06 to 4.25 for LAA-856), airway reactance (β - 0.02, 95% CI - 0.04 to - 0.01 for X5; β 0.30, 95% CI 0.13 to 0.47 for AX; β 1.75, 95% CI 0.85 to 2.66 for Fres), as well as the decrease in expiratory flow rates (β - 3.95, 95% CI - 6.19 to - 1.71 for MMEF%predicted; β - 5.42, 95% CI - 7.88 to - 2.95 for FEF50%predicted) for SAD. All these associations were generally maintained in SAD defined by IOS or spirometry. After stratification of airflow limitation, we further found that the effect of age on LAA-856 was the most significant among almost all subgroups.Conclusions: Aging is significantly associated with the prevalence, increased risk, as well as worse severity of SAD. CT may be a more optimal measure to assess aging-related SAD. The molecular mechanisms for the role of aging in SAD need to be explored in the future. Trial registration Chinese Clinical Trial Registry ChiCTR1900024643. Registered on 19 July 2019. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to compare the biomechanical properties and clinical outcomes of Tile B1 type pubic symphysis diastasis (PSD) treated by percutaneous cannulated screw fixation (PCSF) and reconstruction plate screw fixation (RPSF). Materials and Methods: Finite element analysis (FEA) was used to compare the biomechanical properties between PCSF and RPSF. CT scan data of one PSD patient were used for three-dimensional reconstructions. After a validated pelvic finite element model was established, both PCSF and RPSF were simulated, and a vertical downward load of 600 N was loaded. The distance of pubic symphysis and stress were tested. Then, 51 Tile type B1 PSD patients (24 in the PCSF group; 27 in the RPSF group) were reviewed. Intra-operative blood loss, operative time, and the length of the skin scar were recorded. The distance of pubic symphysis was measured, and complications of infection, implant failure, and revision surgery were recorded. The Majeed scoring system was also evaluated. Results: The maximum displacement of the pubic symphysis was 0.408 and 0.643 mm in the RPSF and PCSF models, respectively. The maximum stress of the plate in RPSF was 1846 MPa and that of the cannulated screw in PCSF was 30.92 MPa. All 51 patients received follow-up at least 18 months post-surgery (range 18-54 months). Intra-operative blood loss, operative time, and the length of the skin scar in the PCSF group were significantly different than those in the RPSF group. No significant differences were found in wound infection, implant failure, rate of revision surgery, distance of pubic symphysis, and Majeed score. Conclusion: PCSF can provide comparable biomechanical properties to RPSF in the treatment of Tile B1 type PSD. Meanwhile, PCSF and RPSF have similar clinical and radiographic outcomes. Furthermore, PCSF also has the advantages of being minimally invasive, has less blood loss, and has shorter operative time and skin scar. [ABSTRACT FROM AUTHOR]

Objective: The current study was undertaken to investigate the relationship between antimüllerian hormone (AMH) and polycystic ovarian syndrome (PCOS) phenotypes and to determine whether AMH is associated with pregnancy outcomes in infertile women undergoing their first in vitro fertilization (IVF) treatment.Methods: We performed a retrospective cohort study of 2973 infertile women, including 418 women with PCOS undergoing their first IVF treatment at a private fertility center from January 2014 to March 2018. Women were stratified into three groups using cutoffs defined by the 25th and 75th percentiles of the serum AMH level: 746 women had AMH ≤ 2.25 ng/mL; 1486 women had AMH between 2.25 to 5.71 ng/mL; and 741 women had AMH > 5.71 ng/mL. Endocrine characteristics, PCOS phenotypes, stimulation outcomes, pregnancy outcomes were compared among these groups. When there were any statistical differences (P < 0.05) among the three groups, Bonferroni test was performed as post-hoc tests to determine where the statistical differences existed. To assess the relationships between AMH and pregnancy outcomes in total patients and PCOS patients, logistic regression analysis, adjusted for potential confounding covariates, were performed.Results: Women with high AMH had greater prevalence of hyperandrogenism (HA), polycystic ovarian morphology (PCOM) and amenorrhea than women with low or average AMH. The clinical pregnancy rate were significantly higher in the high-AMH group compared with low- and average-AMH groups (69.9% vs. 58.8% and 64.7% respectively; P < 0.001). The live birth rate was significantly lower in women with AMH ≤ 2.25 ng/mL compared with average- and high-AMH groups (47.6% vs. 55.2 and 59.5% respectively; P < 0.001). However, after controlling for maternal age, oocyte yield, as well as other confounders, AMH was no longer associated with a higher live birth rate (aOR 1.037, 95% CI 0.853-1.261, P = 0.717; aOR 1.099, 95% CI 0.858-1.408, P = 0.455, respectively) and clinical pregnancy rate (aOR 1.064, 95% CI 0.834-1.359, P = 0.617; aOR 1.181, 95% CI 0.875-1.595, P = 0.276, respectively). Moreover, pregnancy outcomes did not differ in PCOS women according to AMH quartiles.Conclusion: Increased AMH levels associated with PCOS severity and greater ovarian stimulation. However, AMH was not associated with clinical pregnancy rate and live birth rate after controlling for other confounders in women undergoing IVF. Thus, AMH should not be used to alter clinical decisions and exclude patients based on a low or even undetectable AMH value. [ABSTRACT FROM AUTHOR]

Background: A plethora of prognostic biomarkers for esophageal squamous cell carcinoma (ESCC) that have hitherto been reported are challenged with low reproducibility due to high molecular heterogeneity of ESCC. The purpose of this study was to identify the optimal biomarkers for ESCC using machine learning algorithms.Methods: Biomarkers related to clinical survival, recurrence or therapeutic response of patients with ESCC were determined through literature database searching. Forty-eight biomarkers linked to recurrence or prognosis of ESCC were used to construct a molecular interaction network based on NetBox and then to identify the functional modules. Publicably available mRNA transcriptome data of ESCC downloaded from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets included GSE53625 and TCGA-ESCC. Five machine learning algorithms, including logical regression (LR), support vector machine (SVM), artificial neural network (ANN), random forest (RF) and XGBoost, were used to develop classifiers for prognostic classification for feature selection. The area under ROC curve (AUC) was used to evaluate the performance of the prognostic classifiers. The importances of identified molecules were ranked by their occurrence frequencies in the prognostic classifiers. Kaplan-Meier survival analysis and log-rank test were performed to determine the statistical significance of overall survival.Results: A total of 48 clinically proven molecules associated with ESCC progression were used to construct a molecular interaction network with 3 functional modules comprising 17 component molecules. The 131,071 prognostic classifiers using these 17 molecules were built for each machine learning algorithm. Using the occurrence frequencies in the prognostic classifiers with AUCs greater than the mean value of all 131,071 AUCs to rank importances of these 17 molecules, stratifin encoded by SFN was identified as the optimal prognostic biomarker for ESCC, whose performance was further validated in another 2 independent cohorts.Conclusion: The occurrence frequencies across various feature selection approaches reflect the degree of clinical importance and stratifin is an optimal prognostic biomarker for ESCC. [ABSTRACT FROM AUTHOR]

Background: Hymenoptera comprise extremely diverse insect species with extensive variation in their life histories. The Dryinidae, a family of solitary wasps of Hymenoptera, have evolved innovations that allow them to hunt using venom and a pair of chelae developed from the fore legs that can grasp prey. Dryinidae larvae are also parasitoids of Auchenorrhyncha, a group including common pests such as planthoppers and leafhoppers. Both of these traits make them effective and valuable for pest control, but little is yet known about the genetic basis of its dual adaptation to parasitism and predation. Results: We sequenced and assembled a high-quality genome of the dryinid wasp Gonatopus flavifemur, which at 636.5 Mb is larger than most hymenopterans. The expansion of transposable elements, especially DNA transposons, is a major contributor to the genome size enlargement. Our genome-wide screens reveal a number of positively selected genes and rapidly evolving proteins involved in energy production and motor activity, which may contribute to the predatory adaptation of dryinid wasp. We further show that three female-biased, reproductive-associated yellow genes, in response to the prey feeding behavior, are significantly elevated in adult females, which may facilitate the egg production. Venom is a powerful weapon for dryinid wasp during parasitism and predation. We therefore analyze the transcriptomes of venom glands and describe specific expansions in venom Idgf-like genes and neprilysin-like genes. Furthermore, we find the LWS2-opsin gene is exclusively expressed in male G. flavifemur, which may contribute to partner searching and mating. Conclusions: Our results provide new insights into the genome evolution, predatory adaptation, venom evolution, and sex-biased genes in G. flavifemur, and present genomic resources for future in-depth comparative analyses of hymenopterans that may benefit pest control. [ABSTRACT FROM AUTHOR]

Temozolomide (TMZ)-resistance hampers the therapeutic efficacy of this drug for glioblastoma (GBM) treatment in clinic, and emerging evidences suggested that exosomes from GBM-derived stem cells (GSCs) contributed to this process, but the detailed mechanisms are still largely unknown. In the present study, we reported that GSCs derived programmed death-ligand 1 (PD-L1) containing exosomes activated AMPK/ULK1 pathway mediated protective autophagy enhanced TMZ-resistance in GBM in vitro and in vivo. Specifically, we noticed that continuous low-dose TMZ stimulation promoted GSCs generation and PD-L1 containing exosomes (PD-L1-ex) secretion in GBM cells, and that PD-L1-ex inhibited cell apoptosis and promoted cell autophagy to increased TMZ-resistance in GBM cells, which were reversed by co-treating cells with the autophagy inhibitor 3-methyladenine (3-MA). Consistently, upregulation of PD-L1 also increased TMZ-resistance in TS-GBM cells, and silencing of PD-L1 sensitized TR-GBM cells to TMZ. In addition, PD-L1-ex activated AMPK/ULK1 pathway to induce autophagy in TMZ treated GBM cells, and the inhibitors for AMPK (compound C) and ULK1 (SBI-0206965) promoted cell apoptosis in GBM cells co-treated with PD-L1-ex and high-dose TMZ. Finally, we evidenced that PD-L1-ex promoted tumor growth and Ki67 protein expressions to increase TMZ-resistance in GBM in vivo. Collectively, we concluded that GSCs-derived PD-L1-ex activated AMPK1/ULK1 signaling cascade mediated autophagy to increase TMZ-resistance in GBM, and this study provided potential strategies to improve the therapeutic efficacy of TMZ in GBM. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidences have shown that miRNAs are directly or indirectly involved in a variety of biological processes, and closely associated with diverse human diseases, including cardiovascular diseases. SNPs locating within pri/pre-miRNA can affect miRNA processing and binding ability of target genes. MiR-27a, miR-26a-1 miR-100, miR-126 and miR-218 were reported to be associated with pathogenesis of myocardial infarction (MI). Here we aimed to evaluate the potential association of five polymorphisms in these pri/pre-miRNAs with individual susceptibility to MI in a Chinese Han population. Methods: Genotyping was performed in 287 MI cases and 646 control subjects using polymerase chain reactionligase detection reaction (PCR-LDR) method. The association of these SNPs with MI risk was performed with SPSS software. Results: In a logistic regression analysis, we found that AG heterozygote (OR = 0.40, 95% CI = 0.21-0.76, Pa = 0.005) or AA homozygote (OR = 0.40, 95% CI = 0.22-0.75, Pa = 0.004) of pre-miR-27a rs895819 had a reduced susceptibility to MI in comparison with GG homozygote. Similarly, a reduced risk of MI was detected when the AG and AA genotypes were combined (OR = 0.40, 95% CI = 0.22-0.74, Pa = 0.003). However, no significant association between primiR- 26a-1 pri-miR-100, pri-miR-126 and pri-miR-218 polymorphisms and MI risk was observed under the allelic and established genetic models. Further stratified analysis of pre-miR-27a rs895819 revealed a more significant association of AG + AA genotypes with MI risk among younger, male and smoking subjects. Interestingly, AG and AA genotypes of the rs895819 polymorphism conferred about 0.17 mmol/L and 0.18 mmol/L increase in HDL-C levels compared to GG genotype. Conclusions: Our findings suggest that the pre-miR-27a rs895819 polymorphism is associated with MI susceptibility in the Chinese Han population, which probably due to influence the HDL-C levels. [ABSTRACT FROM AUTHOR]

Background: The key-stone-pathogen, Porphyromonas gingivalis associates not only with periodontal diseases but with a variety of other chronic diseases such as cancer. We previously reported an association between the presence of Porphyromonas gingivalis in esophageal squamous cell carcinoma (ESCC) and its progression. We now report the diagnostic and prognostic potential of serum immunoglobulin G and A antibodies (IgG/A) against Porphyromonas gingivalis for ESCC.Methods: An enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of Porphyromonas gingivalis IgG and IgA in 96 cases with ESCC, 50 cases with esophagitis and 80 healthy controls.Results: The median serum levels of IgG and IgA for P. gingivalis were significantly higher in ESCC patients than non-ESCC controls. P. gingivalis IgG and IgA in serum demonstrated sensitivities/specificities of 29.17%/96.90% and 52.10%/70.81%, respectively, and combination of IgG and IgA produced a sensitivity/specificity of 68.75%/68.46%. The diagnostic performance of serum P. gingivalis IgA for early ESCC was superior to that of IgG (54.54% vs. 20.45%). Furthermore, high serum levels of P. gingivalis IgG or IgA were associated with worse prognosis of ESCC patients, in particular for patients with stage 0-IIor negative lymphnode metastasis, and ESCC patients with high levels of both IgG and IgA had the worst prognosis. Multivariate analysis revealed that lymph node status, IgG and IgA were independent prognostic factors.Conclusions: The IgG and IgA for P. gingivalis are potential serum biomarkers for ESCC and combination of IgG and IgA improves the diagnostic and prognostic performance. Furthermore, serum P. gingivalis IgG and IgA can detect early stage ESCC. [ABSTRACT FROM AUTHOR]

Background: This retrospective study and meta-analysis was designed to explore the relationship between E-cadherin (E-cad) expression and the molecular subtypes of invasive non-lobular breast cancer, especially in early-stage invasive ductal carcinoma (IDC). Methods: A total of 156 post-operative cases of early-stage IDCs were retrospectively collected for the immunohistochemistry (IHC) detection of E-cad expression. The association of E-cad expression with molecular subtypes of early-stage IDCs was analyzed. A literature search was conducted in March 2016 to retrieve publications on E-cad expression in association with molecular subtypes of invasive non-lobular breast cancer, and a meta-analysis was performed to estimate the relational statistics. Results: E-cad was expressed in 82.7% (129/156) of early-stage IDCs. E-cad expression was closely associated with the molecular types of early-stage IDCs (P < 0.050); moreover, the molecular subtypes were an independent factor influencing E-cad expression in early-stage IDCs. A total of 12 observational studies (including our study) were included in the meta-analysis. The meta-analytical results show a significantly greater risk of E-cad expression loss in triple-negative breast cancer (TNBC) than in other molecular subtypes (TNBC vs. luminal A: RR = 3.45, 95% CI = 2.79-4.26; TNBC vs. luminal B: RR = 2.41, 95% CI = 1.49-3.90; TNBC vs. HER2-enriched: RR = 1.95, 95% CI = 1.24-3.07). Conclusions: Early-stage IDCs or invasive non-lobular breast cancers with the TNBC molecular phenotype have a higher risk for the loss of E-cad expression than do tumors with non-TNBC molecular phenotypes, suggesting that E-cad expression phenotypes were closely related to molecular subtypes and further studies are needed to clarify the underlying mechanism. [ABSTRACT FROM AUTHOR]

Background: The association between diurnal temperature range (DTR) and hospitalization for exacerbation of chronic respiratory diseases (CRD) was rarely reported.Objectives: To examine the association between DTR and daily hospital admissions for exacerbation of CRD and find out the potential effect of modifications on this association.Method: Data on daily hospitalization for exacerbation of chronic obstructive pulmonary disease (COPD), asthma and bronchiectasis and meteorology measures from 2013 through 2017 were obtained from 21 cities in South China. After controlling the effects of daily mean temperature, relative humidity (RH), particulate matter < 2.5 μm diameter (PM2.5) and other confounding factors, a standard generalized additive model (GAM) with a quasi-Poisson distribution was performed to evaluate the relationships between DTR and daily hospital admissions of CRD in a two-stage strategy. Subgroup analysis was performed to find potential modifications, including seasonality and population characteristics.Result: Elevated risk of hospitalization for exacerbation of CRD (RR = 1.09 [95%CI: 1.08 to 1.11]) was associated with the increase in DTR (the 75th percentile versus the 25th percentile of DTR at lag0-6). The effects of DTR on hospital admissions for CRD were strong at low DTR in the hot season and high DTR in the cold season. The RR (the 75th percentile versus the 25th percentile of DTR at lag0-6) of hospitalization was 1.11 (95%CI: 1.08 to 1.12) for exacerbations of COPD and 1.09 (95%CI: 1.05 to 1.13) for asthma. The adverse effect of DTR on hospitalization for bronchiectasis was only observed in female patients (RR = 1.06 [95%CI: 1.03 to 1.10]).Conclusion: Our study provided additional evidence for the association between DTR and daily hospitalization for exacerbation of CRD, and these associations are especially stronger in COPD patients and in the cold season than the hot season. Preventive measures to reduce the adverse impacts of DTR were needed for CRD patients. [ABSTRACT FROM AUTHOR]

Background: Sub-health status is defined as declines in vitality, physiological function and capacity for adaptation, but without the presence of clinical or sub-clinical disease. We have developed and evaluated a comprehensive questionnaire, the Sub-Health Self-Rating Scale (SSS), to assess sub-health status in university students.Method: The items for the draft questionnaire were discussed in focus groups. The WHOQOL-BREF was selected as the validity reference. From a professional perspective and large sample evaluation, the scale ultimately consisted of 58 items. The reliability and validity of the SSS was examined in undergraduate students and 1000 questionnaires were randomly selected from the samples for expert evaluation.Results: Cronbach's α of the total scale was 0.942. The dimensions of physiological, psychological and social had high reliability: 0.915, 0.856 and 0.850, respectively. Based on scree plot and related theories, there were 10 factors to be extracted. The correlation coefficient between the total scale and sub-scale was high. The dimensions of physiological, psychological and social had high correlations with the total scale: 0.929, 0.803 and 0.774, respectively. The sub-health cut-off point of the total scale was 72; for the physiological field, it was 72; for the psychological field, it was 60; and the social field, it was 56. The fit between the expert evaluation method and the scale method was 0.758. The lower the score, the worse the health condition.Conclusion: We established and evaluated a valid instrument (SSS) that encompasses physiological, psychological and social factors to investigate sub-health status. It is short and easy to complete, and therefore suitable for use with undergraduate students. [ABSTRACT FROM AUTHOR]