Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies.

BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.

A case of linezolid-induced SIADH in elderly and a review of the literature.

INTRODUCTION: Linezolid is a synthetic oxazolidinone antimicrobial drug with a broad spectrum and a unique mechanism of inhibiting resistant pathogenic strains, and it was approved by the Food and Drug Administration (FDA) in April 2000. Several different systemic side effects were reported after the use of this medication. In this article, we report a case in which a syndrome of inappropriate antidiuretic hormone (SIADH) was developed after linezolid treatment was started. CASE PRESENTATION: We present the case of a 79-year-old woman who developed severe hyponatremia during linezolid treatment (0.6 g i.v. q12 h) after undergoing hemiarthroplasty for left femoral neck fracture. The patient's baseline serum sodium upon admission (138 mmol/L) decreased to 118 mmol/L, urine sodium was 102 mmol/L, plasma osmolality was 248 mOsm/kg and urine osmolarity was 310 mOsm/kg at day 4, thus a diagnosis of SIADH was made. The patient was not taking any other medication known to cause SIADH, and she did not present a comorbidity that could explain her condition. Her serum sodium increased to 135 and 137 mmol/L, respectively, 11 and 12 days after cessation of linezolid, strongly suggesting that SIADH was the cause in this case. CONCLUSIONS: This is the fourth case of linezolid-induced SIADH. A thorough workup was essential for the diagnosis to correctly differentiate between SIADH and other causes of hyponatremia, which helped us properly conducting follow-up treatments. SIADH is a rare but serious side effect of linezolid, and practicing physicians should be aware of this complication. It is necessary to periodically monitor the serum sodium.

Community-based participatory research: Suicide prevention for youth at highest risk in Guyana.

Studied mostly in developed countries, the increased prevalence of suicide among youth, worldwide, is a preventable public health concern. Guyana, a developing country in South America, has the highest rate of youth death by suicide. Based on the diathesis-stress model, this community-based study aimed to identify both psychiatric and biological factors associated with repeated suicide attempts among high-risk youth. OBJECTIVE: We measured psychiatric symptoms, childhood traumas, and cortisol to identify correlates with recurrent suicide attempts. METHOD: Poisson regression tested the association between psychiatric symptoms, trauma, and cortisol levels on number of suicide attempts among 50 youths from three child welfare orphanages in Guyana. Sixty-six percent were female, and the average age was 14 years. DSM-5 symptom measure was administered and saliva samples collected. RESULTS: Fifty percent of the youth endorsed suicide attempt. Within this subsample, a minimum of one and maximum of five suicide attempts were self-reported. Participants' number of suicide attempts was positively associated with number of past traumas, psychosis, and depression symptoms. CONCLUSION: Suicide prevention screening among at-risk youth should target severity of psychosis and depression reports and number of traumatic life experiences.

Tyrophagus putrescentiae group 4 allergen allergenicity and epitope prediction

INTRODUCTION AND OBJECTIVES: Allergen-specific immunotherapy (ASIT) is the only allergic disease-modifying therapy available for children and adults, and recombinant allergens are an interesting approach to improve allergy diagnosis and ASIT. Tyrophagus putrescentiae is a common storage mite that produces potent allergens. The aim of this study was to express and characterize recombinant group 4 allergen protein of T. putrescentiae (Tyr p 4), and to further investigate allergenicity and potential epitopes of Tyr p 4. MATERIALS AND METHODS: The cDNA encoding Tyr p 4 was generated by RT-PCR and subcloned into pET-28a(+) plasmid. The plasmid was then transformed into E. coli cells for expression. After purification by nickel affinity chromatography and identification by SDS-PAGE, recombinant Tyr p 4 protein was used for a skin prick test and an ELISA to determine the allergic response. RESULTS: Study participants' allergic response rate to Tyr p 4 protein was 13.3% (16/120). Eight B-cell epitopes and three T-cell epitopes of Tyr p 4 were predicted. CONCLUSIONS: Similar to group 4 allergens of other species of mite, allergenicity of Tyr p 4 is weak. The expression, characterization and epitope prediction of recombinant Tyr p 4 protein provide a foundation for further study of this allergen in the diagnosis and ASIT of storage mite allergy

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Tyrophagus putrescentiae group 4 allergen allergenicity and epitope prediction.

INTRODUCTION AND OBJECTIVES: Allergen-specific immunotherapy (ASIT) is the only allergic disease-modifying therapy available for children and adults, and recombinant allergens are an interesting approach to improve allergy diagnosis and ASIT. Tyrophagus putrescentiae is a common storage mite that produces potent allergens. The aim of this study was to express and characterize recombinant group 4 allergen protein of T. putrescentiae (Tyr p 4), and to further investigate allergenicity and potential epitopes of Tyr p 4. MATERIALS AND METHODS: The cDNA encoding Tyr p 4 was generated by RT-PCR and subcloned into pET-28a(+) plasmid. The plasmid was then transformed into E. coli cells for expression. After purification by nickel affinity chromatography and identification by SDS-PAGE, recombinant Tyr p 4 protein was used for a skin prick test and an ELISA to determine the allergic response. RESULTS: Study participants' allergic response rate to Tyr p 4 protein was 13.3% (16/120). Eight B-cell epitopes and three T-cell epitopes of Tyr p 4 were predicted. CONCLUSIONS: Similar to group 4 allergens of other species of mite, allergenicity of Tyr p 4 is weak. The expression, characterization and epitope prediction of recombinant Tyr p 4 protein provide a foundation for further study of this allergen in the diagnosis and ASIT of storage mite allergy.

miR-137 alleviates focal cerebral ischemic injury in rats by regulating JAK1/STAT1 signaling pathway.

The repairing effect and potential mechanism of miR-137 on cerebral ischemic injury in rats was investigated. The volume of cerebral infarction and calculated brain water content was detected by triphenyltetrazolium chloride staining. The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay. The pathological damage of brain tissue was analyzed by hematoxylin and eosin and Nissl staining. The apoptosis in ischemic brain tissue was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. The levels of STAT1 and JAK1 proteins were analyzed by Western blot. The expression of miR-137 in primary hippocampal neurons was detected by reverse transcription polymerase chain reaction. miR-137 overexpression significantly improved brain damage in rats. miR-137 overexpression can reduce the expression of TNF-α, IL-1ß, and IL-6. miR-137 overexpression can reduce the degree of brain tissue damage and inhibit the expression of JAK1 and STAT1 proteins. miR-137 overexpression can reduce oxygen-glucose deprivation (OGD)/R-induced cell damage, improve cell proliferation, and reduce apoptotic rate. JAK1 and STAT1 protein expression was inhibited in hippocampal neurons after OGD/R treatment after transfection with miR-137 mimic. After the addition of the Filgotinib inhibitor, the levels of JAK1 and STAT1 proteins were significantly reduced. The results suggested that miR-137 overexpression can effectively improve ischemic injury after focal cerebral ischemia and protect against by inhibiting JAK1/STAT1 pathway.

Gefitinib promotes CXCR4-dependent epithelial to mesenchymal transition via TGF-ß1 signaling pathway in lung cancer cells harboring EGFR mutation.

PURPOSE: Epithelial to mesenchymal transition (EMT) plays an important role in acquired resistance to gefitinib in lung cancer. This study aimed to explore the underlying mechanism of gefitinib-induced EMT in lung adenocarcinoma cells harboring EGFR mutation. METHODS: CXC chemokine receptor 4 (CXCR4) expression was determined through qRT-PCR, Western blot and flow cytometry assays in lung cancer cell line (PC9) bearing mutated EGFR. Functional role of CXCR4 was inhibited applying siRNAs as well as the specific antagonist AMD3100. The expression of EMT markers was determined, and the migration of PC9 cells was measured with transwell assay. RESULTS: We found that gefitinib promoted the migratory capacity of PC9 cells in vitro, which correlated with EMT occurrence through upregulation of CXCR4. Blocking CXCR4 significantly suppressed gefitinib-induced enhancement of migration and EMT. Moreover, we determined that the upregulation of CXCR4 by gefitinib was dependent on TGF-ß1/Smad2 signaling activity. CONCLUSIONS: Our study suggested a potential mechanism by which gefitinib induced EMT in cells harboring EGFR mutation through a pathway involving TGF-ß1 and CXCR4. Thus, the combination of CXCR4 antagonist and TGFßR inhibitors might provide an alternative strategy to overcome progression of lung cancer after gefitinib treatment.

Potential roles of lncRNA-Cox2 and EGR1 in regulating epidural fibrosis following laminectomy.

OBJECTIVE: Epidural fibrosis, one of the common complications after spinal surgery, seriously affects the surgical decompression effect. Effectively inhibiting the fibrous tissue hyperplasia is pivotal to reduce the scar adhesion. Previous studies showed that early growth response 1 (EGR1) is associated with the fibroblast reactivity induced by transforming growth factor-beta (TGF-ß) and plays a vital regulatory role in scar formation; however, the upstream targets and mechanisms still remain unclear. In this work, it was found that the level of long non-coding ribonucleic acid (lncRNA)-cyclooxygenase-2 (COX2) was significantly negatively correlated with EGR1 expression and the severity of the scar. Therefore, it was conjectured that lncRNA-COX2 may decrease fibroplasia and scar formation by negatively regulating EGR1. MATERIALS AND METHODS: TGF-ß was used to activate the embryonic and adult rat fibroblasts. Rats underwent laminectomy to establish the epidural fibrosis model. The changes in the levels of fibroplasia-related genes were measured and analyzed through messenger RNA (mRNA), lncRNA, and micro RNA expression profile chips. Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) was applied to determine the levels of EGR1 and lncRNA-COX2, and Western blotting was adopted to detect the content of EGR1, collagen I (Col-1), Col-3, and alpha-smooth muscle actin (α-SMA). The scar formation was reflected by hematoxylin and eosin (HE) staining and Masson staining, and the expression level of α-SMA in the scar tissues was measured via immunohistochemistry. Finally, micro-magnetic resonance imaging (MRI) was utilized to examine the different degrees of epidural fibroplasia. RESULTS: It was found that the reactivity of embryonic rat fibroblasts to the TGF-ß stimulation was different from that of adult rat fibroblasts. LncRNA-COX2 was highly expressed in the embryonic rat fibroblasts, but lowly expressed in the adult rat fibroblasts, which had negative correlations with the EGR1 level in embryonic and adult rat fibroblasts. In addition, it was revealed that the expression of EGR1 in the adult rat fibroblasts was remarkably higher than that in the embryonic rat fibroblasts after the activation with TGF-ß. Meanwhile, the level of lncRNA-COX2 was lowered after the activation, especially in the adult rat fibroblasts. It was discovered in the in-vivo model that the degree of fibroplasia was positively associated with EGR1 level and negatively correlated with lncRNA-COX2 level. CONCLUSIONS: The results of this research elucidated that the down-regulation of lncRNA-COX2 is involved in the epidural scar formation and related to the elevated EGR1 level which regulates the activation of fibroblasts and secretion of massive extracellular matrixes, suggesting that lncRNA-COX2 may modulate the role of fibroblasts in scar formation as an upstream action target of EGR1.

Clinical risk factors among youth at high risk for suicide in South Africa and Guyana.

INTRODUCTION: Suicide is the second leading cause of death among youth worldwide, but low- and middle-income countries (LMICs) account for 78% of all suicides. The LMICs South Africa and Guyana rank high in the global suicide rates. To better understand and prevent suicide among the youth, the present study targets youths at high risk for suicide, in an LMIC, to contextually and representatively identify clinical risk factors for suicide. METHODS: One hundred-ninety youths, aged 11-21, separated from biological parents at the time of assessment, in South Africa and Guyana, were administered the Child Behavior Checklist and Behavior Assessment System for Children to assess clinical symptoms. The youths were asked about current suicide ideation and previous attempt(s). Self-report responses to clinical items yielded scale scores for depression, social stress, atypicality, somatization, anxiety, and ADHD. Using an integrative data analytic technique, clinical scale scores were standardized and used to predict suicidal behaviors in a binary logistic regression analysis. RESULTS: Approximately 22% of Black South African youths and 60% of Guyanese youths endorsed suicide ideation and attempt or suicide attempt only. In fully adjusted analyses, the odds of atypicality and somatization were 1.96 and 1.67 times greater among the youths who endorsed suicidal ideation when compared with those who did not (p < .04). Youth social stress was significantly associated with the suicide attempt, controlling for model covariates (odds ratio [OR], 1.88, p = .05). Gender moderated the effect of somatization on youth suicide. CONCLUSION: Our results contextualize how social stress, atypicality, and somatization relate to LMIC youth suicide. Further study on high-risk samples will contribute to generalizable suicide-prevention models.

LncSNHG16 promotes proliferation and migration of osteosarcoma cells by targeting microRNA-146a-5p.

OBJECTIVE: The aim of this study was to elucidate the regulatory role of lncSNHG16 in the progression of osteosarcoma (OS) and its underlying mechanism. MATERIALS AND METHODS: Expressions of lncSNHG16, microRNA-146a-5p and NOVA1 in OS tissues and adjacent normal tissues were determined by quantitative Real-time polymerase chain reaction (qRT-PCR). Their expressions in OS cell lines were detected by qRT-PCR as well. We analyzed the relationship between lncSNHG16 expression and tumor stage, diagnosis and survival prognosis of OS patients, respectively. Cell counting kit-8 (CCK-8) and transwell experiments were conducted to explore proliferative and migratory changes of OS cells. Dual-luciferase reporter assay was used to verify the binding relationship of lncSNHG16 to microRNA-146a-5p, and microRNA-146a-5p to NOVA1. Finally, rescue experiments were performed to elucidate the regulatory effect of lncSNHG16 on the cellular behaviors of OS cells. RESULTS: LncSNHG16 was highly expressed in OS tissues and cell lines. Its expression was positively correlated with the tumor stage of OS patients. Receiver operating characteristic (ROC) curves suggested that lncSNHG16 can be used as a clinical indicator to distinguish OS patients from healthy controls. Survival analysis indicated a negative correlation between lncSNHG16 expression and survival of OS patients. Overexpression of lncSNHG16 enhanced the proliferative and migratory potentials of OS cell lines 143B and MNNG/HOS. MicroRNA-146a-5p was predicted to be the target gene of lncSNHG16, which was lowly expressed in OS tissues and cell lines. Overexpression of lncSNHG16 downregulated the expression of microRNA-146a-5p in 143B and MNNG/HOS cells. Furthermore, we verified that lncSNHG16 could bind to microRNA-146a-5p. The promotive role of lncSNHG16 in proliferative and migratory potentials of OS cells was reversed by microRNA-146a-5p. Subsequently, NOVA1 was predicted to be the target gene of microRNA-146a-5p, and was further verified by dual-luciferase reporter gene assay. Correlation analysis showed that microRNA-146a-5p expression was negatively correlated with NOVA1 expression in OS. More importantly, NOVA1 reversed the inhibitory effect of microRNA-146a-5p on the proliferative and migratory capacities of 143B and MNNG/HOS cells. CONCLUSIONS: LncSNHG16 is highly expressed in OS tissues and cell lines, participating in the development of OS by downregulating microRNA-146a-5p to upregulate NOVA1 expression.

A SUVmax-based propensity matched analysis of stereotactic body radiotherapy versus surgery in stage I non-small cell lung cancer: unveiling the role of 18F-FDG PET/CT in clinical decision-making

Background: The value of maximum standard uptake value (SUVmax) was overlooked in current studies comparing stereotactic body radiotherapy (SBRT) versus surgery for stage I non-small cell lung cancer (NSCLC). Herein, we aimed to compare the 3-year outcomes based on patients for whom SUVmax were available, and to explore the role of SUVmax in clinical decision-making. Methods: From January 2010 to June 2016, data of eligible patients were collected. Patient variables and clinical outcomes were compared in both unmatched and matched groups using propensity score matching (PSM). Multivariate analysis was performed for predictors of poor outcome. The relationship between treatment approach and survival outcome was also evaluated in subgroup patients stratified by SUVmax level. Results: A total of 425 patients treated with either surgery (325) or SBRT (100) were included. Patients receiving SBRT were significantly older, had a higher level of SUVmax and were more likely to have tumor of centrally located. Multivariate analysis showed that SUVmax and tumor size were significant predictors for 3-year OS, LRC, and PFS, while better PFS was also related to peripheral tumor and surgery. The result of PSM analysis also showed that compared to SBRT, surgery could only achieve better PFS. Subgroup analysis indicated that surgery had added advantage of 3-year LRC and PFS for patients in high SUVmax group (SUVmax > 8), but not in low SUVmax group. Conclusions: The study found a superior PFS after surgery while OS and LRC did not differ between SBRT and surgery. Surgery should be recommended for tumor of high SUVmax

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Comparative study between mini-open TLIF via Wiltse's approach and conventional open TLIF in lumbar degenerative diseases.

OBJECTIVE: To compare the clinical effects, operation safety and radiation exposure of mini-open TLIF via Wiltse's approach (MOTLIF) and conventional open TLIF (COTLIF) in the treatment of single-segment lumbar degenerative disease via the prospective control study. PATIENTS AND METHODS: A total of 77 patients were enrolled from November 2012 to July 2014, including 42 patients in the mini-open group (MOTLIF) and 35 patients in the COTLIF group. Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) scores before operation, operation time, intraoperative blood loss, postoperative drainage volume, blood transfusion rates, postoperative bedridden time, postoperative hospital stays, intraoperative fluoroscopic time, levels of serum creatine phosphokinase (CPK) before operation, 3 days and 1 week after operation, VAS scores before operation, 3 days and 1 week after operation, and ODI and VAS scores in the last follow-up between the two groups were compared. RESULTS: There were significant differences between the two groups in the operation time, intraoperative blood loss, postoperative drainage, blood transfusion rates, postoperative bedridden time, postoperative hospital stays and intraoperative fluoroscopic time; all indicators in MOTLIF group were superior to those in COTLIF group (p<0.05). There were no significant differences between the two groups in levels of serum CPK before operation and 1 week after operation (p>0.05). However, 3 days after operation, the level of serum CPK in COTLIF group was increased more significantly than that in MOTLIF group (647.4±178.6 vs. 467.4±189.4). There were no differences between the two groups in ODI and VAS scores before operation; ODI score in MOTLIF group in the last follow-up was significantly superior to that in COTLIF group (p>0.05). And VAS scores at 3 days and 1 week after operation and the last follow-up in MOTLIF group were superior to those in COTLIF group (p<0.05). CONCLUSIONS: Compared with the conventional open TLIF, mini-open TLIF via Wiltse's approach using the self-designed operating apparatus is characterized by the convenient operation, small trauma and quick recovery after operation. At the same time, the radiation exposure is lower and long-term follow-up effect is superior. Its short-term and long-term effects in the treatment of lower lumbar degenerative disease are also superior.

Biomechanical strength impact of lateral wall breach on spinal pedicle screw fixation.

OBJECTIVE: The purpose of our study was to make a comparison between the fixation strength of optimum placed pedicle screw (OS) and re-directionally accurate placed pedicle screw (RS) after lateral pedicle breach. PATIENTS AND METHODS: A total of 30 fresh lumbar vertebrae (L1-5) were gained from 6 male or female pigs weighing about 100 kg, which were divided into 2 groups according to different ways of pedicle screws placement: OS group (n=30) and RS group (n=30). MTS machine was employed to detect the screw loosening and axial pullout. We examined seating torque, screw-loosening force, the maximal torque and post-loosening axial pullout in each pedicle screw. RESULTS: Maximal insertion torque of OS was (111.6±8.4) N•cm and RS was (79.0±6.3) N•cm, which indicated a significant difference (Z=3.012, p=0.003). Seating torque of OS and RS were (85.9±5.6) N•cm and (60.3±4.8) N•cm separately, and the difference was statistically significant (Z=2.799, p=0.006). Screw loosening force of OS and RS were (75.9±7.0) N and (52.4±6.3) N respectively, and the difference was statistically significant (Z=2.652, p=0.003). Post-loosening axial pullout force of OS and RS were (328.5±11.3) N and (269.1±9.6) N separately, demonstrating that the difference was statistically significant (Z=2.865, p=0.004). CONCLUSIONS: RS placement is an alternative for remediation following a lateral wall breach evidenced by significantly decreased seating torque, screw loosening force, the maximal torque and post-loosening axial pullout compared with OS.

A multi-level drill guide template improves the accuracy of pedicle screw placement in lumbar spine.

OBJECTIVE: Free-hand technique is widely used in pedicle screw placement for lumbar spine and generally safe; however, screw malposition still occurs. To develop a novel multi-level drill guide template for pedicle screw placement in lumbar spine and evaluate its accuracy. MATERIALS AND METHODS: Twelve lumbar cadaveric specimens were randomly allocated into guide template group (n=6) and free-hand group (n=6). Computed tomography (CT) scans were obtained for reconstruction of three-dimensional (3D) model of each lumbar vertebra, and further an individual guide template was designed. Then the templates and their corresponding vertebra were developed by rapid prototyping (RP) technology. With the guide of the templates, screws were inserted via mini-open Wiltse approach. The positions of the screws were assessed based on postoperative CT images. RESULTS: In total, 120 pedicle screws inserted (guide template group: n=60 vs. free-hand group: n=60). For all 30 vertebras in the guide template group, all pre-designed personalized drill guide templates can be fitted into the facet joints of each vertebra well. Furthermore, our results revealed a significant improvement for the guide template group in the accuracy rate (p=0.026). CONCLUSIONS: Armed with advantages of minimal invasion, enhanced accuracy and safety, the novel technique of multi-level drill guide template can be properly applied in pedicle screw placement for lumbar spine and promises to be a potential option in clinical application.

Nomogram to predict lymph node metastasis in patients with early oesophageal squamous cell carcinoma.

BACKGROUND: Lymph node status is crucial in determining the prognosis for early oesophageal squamous cell carcinoma (SCC). This study aimed to develop and validate a nomogram for the prediction of lymph node metastasis in patients with early SCC. METHODS: A prediction model was developed in a derivation cohort of patients with clinicopathologically confirmed early SCC. Patients who underwent oesophagectomy for pT1 SCC between January 2010 and December 2013 were identified from an institutional database. Risk factors for lymph node metastasis were assessed using a binary logistic regression modelling technique. A nomogram for the prediction of lymph node metastasis was constructed using the results of multivariable analyses. For internal validation, bootstraps with 1000 resamples were performed. The predictive performance of the nomogram was measured by Harrell's concordance index (C-index). An independent cohort from the same hospital was used to validate the nomogram. This cohort included consecutive patients with early SCC who underwent oesophagectomy from January 2014 to December 2015. RESULTS: The derivation cohort included 281 patients. Four variables associated with lymph node metastasis were included in the model: depth of tumour invasion (odds ratio (OR) 4·37, 95 per cent c.i. 1·59 to 12·03; P = 0·004), grade of differentiation (OR 4·47, 1·02 to 19·70; P = 0·048), tumour size (OR 2·52, 1·11 to 5·75; P = 0·028) and lymphovascular invasion (OR 6·58, 2·54 to 17·05; P < 0·001). The C-index was 0·790 (95 per cent c.i. 0·717 to 0·864) in the derivation cohort and 0·789 (0·709 to 0·869) for the validation cohort (198 patients). CONCLUSION: A validated nomogram for patients with early oesophageal SCC can predict the risk of lymph node metastasis.

MiR-299-5p targets cell cycle to promote cell proliferation and progression of osteosarcoma.

OBJECTIVE: Osteosarcoma is a common primary bone tumor with high mortality. MicroRNA (miRNA, miR) is a small RNA with 20-25 nucleotides, which could regulate diverse biological processes by targeting 3'-UTR of gene to degrade it. MiR-299-5p has been reported to participate in the progression of many diseases, but the role in osteosarcoma is still uncertain. The aim of this work was to investigate the expression of miR-299-5p in osteosarcoma and its clinical significance. MATERIALS AND METHODS: The datasets of osteosarcoma miRNA was searched in Gene Expression Omnibus (GEO) datasets, including GSE65071, GSE39040, and GSE39055. Osteosarcoma U2 and MG-63 cells were cultured in our study. Cell proliferation level after transfection was detected by using Cell Counting Kit-8 (CCK8) and colon formation assay. Cell cycles were explored using flow cytometer and cell protein expression levels after that the transfection was detected by Western blotting. RESULTS: We found that ROC curve analysis showed that miR-299-5p was a sensitivity diagnostic criteria and GSEA indicated that miRNA-299-5p may regulate cell cycle. Gain of function assay showed that miR-299-5p promotes cell cycle transition and proliferation. Reversely, the opposite results were observed with loss of function assay. At last, Western blotting assay showed that miR-299-5p may promote cell cycle transition by regulating CDK family.

A SUVmax-based propensity matched analysis of stereotactic body radiotherapy versus surgery in stage I non-small cell lung cancer: unveiling the role of 18F-FDG PET/CT in clinical decision-making.

BACKGROUND: The value of maximum standard uptake value (SUVmax) was overlooked in current studies comparing stereotactic body radiotherapy (SBRT) versus surgery for stage I non-small cell lung cancer (NSCLC). Herein, we aimed to compare the 3-year outcomes based on patients for whom SUVmax were available, and to explore the role of SUVmax in clinical decision-making. METHODS: From January 2010 to June 2016, data of eligible patients were collected. Patient variables and clinical outcomes were compared in both unmatched and matched groups using propensity score matching (PSM). Multivariate analysis was performed for predictors of poor outcome. The relationship between treatment approach and survival outcome was also evaluated in subgroup patients stratified by SUVmax level. RESULTS: A total of 425 patients treated with either surgery (325) or SBRT (100) were included. Patients receiving SBRT were significantly older, had a higher level of SUVmax and were more likely to have tumor of centrally located. Multivariate analysis showed that SUVmax and tumor size were significant predictors for 3-year OS, LRC, and PFS, while better PFS was also related to peripheral tumor and surgery. The result of PSM analysis also showed that compared to SBRT, surgery could only achieve better PFS. Subgroup analysis indicated that surgery had added advantage of 3-year LRC and PFS for patients in high SUVmax group (SUVmax > 8), but not in low SUVmax group. CONCLUSIONS: The study found a superior PFS after surgery while OS and LRC did not differ between SBRT and surgery. Surgery should be recommended for tumor of high SUVmax.

Suicide behaviour among Guyanese orphans: identification of suicide risk and protective factors in a low- to middle-income country.

OBJECTIVE: Suicide is the leading cause of death among youth in Guyana, a low- and middle-income country (LMIC), which globally ranks first in female adolescent suicides over the last decade. Worldwide, Guyana has experienced the largest increase in youth suicide, despite focused public health efforts to reduce suicide. Further, youth in Guyana, who are clients of the orphanage system and have faced early childhood trauma, may have an additive risk for suicide. Guided by an ideation-to-action theoretical framework for suicide prevention, the goal of the proposed research study is to describe and identify risk and protective factor correlates of youth suicidal behaviour among those at highest risk for suicide - orphans who reside in a LMIC institutional setting. METHODS: In a preliminary sample of 25 orphan youth, one licensed psychologist and two social workers administered the DSM-5 Level 1 Cross-Cutting Symptom Measure and Behavioural Assessment Schedule for Children, 2nd Edition (BASC-2) during a semi-structured interview. RESULTS: Nine of the 25 (36%) orphans reported a previous suicide attempt. Youth who endorsed suicidal behaviour had clinically elevated interpersonal relations scale scores when compared to youth who did not. CONCLUSIONS: Interpersonal skills may be protective for youth at highest risk for suicide.

Functions of microRNAs in osteoporosis.

Osteoporosis (OP) is a kind of disease with a 25% incidence, characterized by the bone mass loss, bone microstructure damage, increased bone fragility, and easy fracture. miRNA plays an important regulatory role in the process of bone remodeling, especially in the regulation of differentiation and function of osteoblasts and osteoclasts, and the development and progression of OP and other bone diseases. In the future, it is expected to delay the bone loss and promote the bone remodeling via the overexpression or inhibition of specific miRNAs in specific tissues, thereby treating OP.

MiR-146a inhibits proliferation and induces apoptosis in murine osteoblastic MC3T3-E1 by regulating Bcl2.

OBJECTIVE: The dysregulation of proliferation and apoptosis plays a significant role in the pathogenesis of hormone-induced osteonecrosis of femoral head (ONFH). The research aimed to explore the regulatory role of miR-146a in dexamethasone (DEX)-induced proliferation and apoptosis change in MC3T3-E1 cells from murine osteoblastic. MATERIAL AND METHODS: In this study, MC3T3-E1 was co-cultured with 10-7 DEX for 6 h, then RT-PCR was employed to test the expression level of miR-146a and Bcl2. CCK8 assay and flow cytometry were adopted to verify miR-146a could regulate proliferation and apoptosis. After transfected MC3T3-E1 with mimics and inhibitor, RT-PCR and Western blot was used to detect Bcl2 expression level. RESULTS: In DEX treated MC3T3-E1 cells showed higher MiR-146a expression level and lower Bcl2 expression level. MiR-146a could inhibit proliferation and promotes apoptosis in murine osteoblastic MC3T3-E1 cells. Additionally, Bcl2 gene is regulated by MiR-146a. CONCLUSIONS: The MiR-146a expression level increased, while Bcl2 has low expression level in dexamethasone treated MC3T3-E1 cells. MiR-146a regulates proliferation and apoptosis of mouse bone cells. The low expression level of Bcl2 in DEX treated MC3T3-E1 cells is caused by increased MiR-146a level.