[Multi-omics combined test performance effectiveness on opportunistic screening of high-risk liver cancer population].

Objective: To validate the performance of a multi-omics combined test for early screening of high-risk liver cancer populations. Methods: 173 high-risk patients with liver cancer were prospectively screened in a real-world setting, and 164 cases were finally enrolled. B-ultrasound, alpha-fetoprotein (AFP), and HCC screens were conducted in all patients. A multi-omics early screening test was performed for liver cancer in combination with multi-gene methylation, TP53/TERT/CTNNB1 mutations, AFP, and abnormal prothrombin (PIVKA-II). Differences in rates were compared using the chi-square test, adjusted chi-square test, or Fisher's exact probability method for count data. A non-parametric rank test (Mann-Whitney) was used to compare the differences between the two groups of data. Results: The HCCscreen detection had a sensitivity of 100% for liver cancer screening, 93.8% for liver cancer and precancerous diseases, 34.1% for positive predictive value, 99.2% for negative predictive value, and 0.89 for an area under the curve (AUC). Parallel detection of AFP, AFP+B-ultrasound, and methylation+mutation had a sensitivity/specificity and AUC of 31.3%/88.5% (AUC=0.78), 56.3%/88.2% (AUC=0.86), and 81.3%/82.4 % (AUC=0.84). At the same time, the disease severity range was significantly correlated with the methylation+mutation score, HCCscreen score, or positive detection rate (PDR). There was no significant correlation between AFP serum levels and methylation+mutation or HCCscreen scores, while there was a significant linear correlation between methylation+mutation scores and HCCscreen scores (r = 0.73, P < 0.001). Conclusion: In real-world settings, HCCscreen shows high sensitivity for screening opportunistic, high-risk liver cancer populations. Furthermore, it may efficaciously detect liver cancer and precancerous diseases, with superior performance to AFP and AFP+ultrasound. Hence, HCCscreen has the potential to become an effective screening tool that is superior to existing screening methods for high-risk liver cancer populations.

First Report of Fusarium Root Rot of Tobacco Caused by Fusarium fujikuroi in Guangdong Province, China.

From March to June 2022, Fusarium tobacco root rot broke out in Shaoguan Guangdong Province, China, affecting approximately 15% of tobacco production fields, with an incidence of 24% to 66%. In the early stage, the lower leaves showed chlorosis, and the roots became black. In the later stage, the leaves became browned and withered, the root cortices were broken and shed, and only a small number of roots were left. Eventually, the entire plant died. Six diseased plant samples (cv. yueyan 97) from Shaoguan (113.8°E, 24.8°N) were collected as test materials. The diseased root tissues (4×4 mm) were surface-sterilized using 75% ethanol for 30 s and 2% NaOCl for 10 min, rinsed 3 times with sterile water and incubated for 4 days on potato dextrose agar (PDA) medium at 25 °C. Fungal colonies were subcultured on fresh PDA, grown for the next 5 d and purified by single-spore separation. Eleven isolates with similar morphological characteristics were obtained. Their colonies were white and fluffy, and the bottoms of the culture plates were pale pink after 5 days of incubation. The macroconidia were slender, slightly curved and measured 18.54~45.85 µm×2.35~3.84 µm (n=50), with 3 to 5 septa. The microconidia were oval or spindle shaped, with one to two cells, and measured 5.56~16.76 µm×2.32~3.86 µm (n=50). Chlamydospores were absent. Such characteristics are typical of the genus Fusarium (Booth C, 1971). The SGF36 isolate was chosen for further molecular analysis. The TEF-1α and ß-tubulin genes (Pedrozo et al.2015) were amplified. Based on a phylogenetic tree (neighbor-joining method and 1,000 bootstrap values) obtained using multiplex alignments of concatenations of these two genes from 18 Fusarium species, SGF36 was grouped into a clade with Fusarium fujikuroi strain 12-1 (MK443268.1/MK443267.1) and F. fujikuroi isolate BJ-1 (MH263736.1/MH263737.1). To further identity the isolate, five additional gene sequences (rDNA-ITS (OP862807.1), RPB2, histone 3, calmodulin, and mitochondrial small subunit) (Pedrozo et al.2015), were subjected to BLAST searches in GenBank, and the results indicated that they were most similar to F. fujikuroi sequences, with sequence identities greater than 99%. The phylogenetic tree obtained using six genes except mitochondrial small subunit gene showed that SGF36 was grouped together with four F. fujikuroi strains to form a single clade. Pathogenicity was determined by the inoculation of wheat grains with fungi in potted tobacco plants. The SGF36 isolate was inoculated onto sterilized wheat grains, which were then incubated at 25 °C for 7 d. Thirty wheat grains with fungi were added to 200 g of sterilized soil, which was then mixed well and placed into pots. One six-leaf-stage tobacco seedling (cv. yueyan 97) was planted in each pot. A total of 20 tobacco seedlings were treated. Another 20 control seedlings were treated with wheat grains without fungi. All seedlings were placed in a greenhouse at 25 °C with 90% relative humidity. After 5 d, the leaves of all inoculated seedlings showed chlorosis, and the roots became discolored. No symptoms were observed in the controls. The fungus was reisolated from symptomatic roots and confirmed to be F. fujikuroi based on the TEF-1α gene sequence. No F. fujikuroi isolates were recovered from control plants. F. fujikuroi was previously reported to be associated with rice bakanae disease (Ram et al., 2018), soybean root rot (Zhao et al., 2020) and cotton seedling wilt (Zhu et al., 2020). To our knowledge, this is the first report of F. fujikuroi causing root wilt on tobacco in China. The identification of the pathogen may help to establish appropriate measures for controlling this disease.

Correlation study between apparent diffusion coefficients and the prognostic factors in breast cancer.

AIM: To analyse the correlation between apparent diffusion coefficients (ADC) derived from intratumoural and peritumoural regions with prognostic factors and immune-inflammatory markers in breast cancer (BC). MATERIALS AND METHODS: In this retrospective study, 89 patients (age range, 28-66 years; median, 45 years) with a diagnosis of invasive BC who underwent routine blood tests and multiparametric magnetic resonance imaging (MRI) were enrolled. The study cohort was stratified according to tumour maximum cross-section ≥20 mm, lymph node metastasis (LNM), time-signal intensity curve (TIC) type, and receptor status. Minimum, maximum, mean, and heterogeneity values of tumour ADC (ADCtmin, ADCtmax, ADCtmean, and ADCheter), maximum values of peritumoural ADC (ADCpmax), and the ratio of peritumoural-tumour ADC (ADCratio) were obtained on the ADC maps. Linear regression analyses were performed to investigate the correlation between immune-inflammatory markers, prognostic factors and ADC values. RESULTS: HER-2 was positively associated with ADCtmax, ADCtmean, and ADCpmax values (ß = 0.306, p=0.004; ß = 0.283, p=0.007; ß = 0.262, p=0.007, respectively), while platelet-to-lymphocyte ratio (PLR) was positively associated with ADCpmax and ADCratio values (ß = 0.227, p=0.020; ß = 0.231, p=0.020, respectively). Among ADC parameters, ADCpmax showed the highest predictive values for evaluating the presence of LNM (AUC, 0.751; sensitivity, 70.4%; specificity, 77.1%). CONCLUSION: The ADCpmax value could provide additional assistance in predicting prognostic factors of BC.

Longitudinal associations between alcohol use, smoking, genetic risk scoring and symptoms of depression in the general population: a prospective 6-year cohort study.

BACKGROUND: Alcohol consumption, smoking and mood disorders are leading contributors to the global burden of disease and are highly comorbid. Yet, their interrelationships have remained elusive. The aim of this study was to examine the multi-cross-sectional and longitudinal associations between (change in) smoking and alcohol use and (change in) number of depressive symptoms. METHODS: In this prospective, longitudinal study, 6646 adults from the general population were included with follow-up measurements after 3 and 6 years. Linear mixed-effects models were used to test multi-cross-sectional and longitudinal associations, with smoking behaviour, alcohol use and genetic risk scores for smoking and alcohol use as independent variables and depressive symptoms as dependent variables. RESULTS: In the multi-cross-sectional analysis, smoking status and number of cigarettes per day were positively associated with depressive symptoms (p < 0.001). Moderate drinking was associated with less symptoms of depression compared to non-use (p = 0.011). Longitudinally, decreases in the numbers of cigarettes per day and alcoholic drinks per week as well as alcohol cessation were associated with a reduction of depressive symptoms (p = 0.001-0.028). Results of genetic risk score analyses aligned with these findings. CONCLUSIONS: While cross-sectionally smoking and moderate alcohol use show opposing associations with depressive symptoms, decreases in smoking behaviour as well as alcohol consumption are associated with improvements in depressive symptoms over time. Although we cannot infer causality, these results open avenues to further investigate interventions targeting smoking and alcohol behaviours in people suffering from depressive symptoms.

[Summary of community smoking cessation intervention theory].

This paper analyzes the literatures about community-based smoking cessation interventions in recent decades and introduces the effectiveness of cessation interventions developed under different theoretical frameworks applied in the community. Because of the severe smoking prevalence in China and the shortage of existing smoking cessation services, the application of smoking cessation services in reducing the smoking rate in Chinese is discussed to provide a reference for the theoretical framework and practical application of community smoking cessation intervention research in China.

[Long-term observation of the effect of atlantoaxial fusion on the growth and development of children's cervical spine].

Objective: To explore the effect of atlantoaxial fusion on the growth and development of children's cervical spine. Methods: The clinical data of 12 children with atlantoaxial dislocation who underwent posterior atlantoaxial fusion at Department of Orthopaedics,the 909th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from June 2002 to September 2013 were retrospective analyzed. There were 7 males and 5 females,with age of (8.1±3.1)years (range:3 to 13 years).Nine cases were traumatic and 3 cases were congenital malformations,1 of the children had Down syndrome. All children underwent posterior atlantoaxial fusion. Furthermore,the information of the height and anteroposterior width of the cervical vertebral bodies and vertical growth rate of the fusion mass were collected from all patients immediately postoperatively and during the follow-up.The range of motion in cervical spine were collected preoperatively and during follow-up period. Data were compared using independent sample t test, paired sample t test and repeated-measurement. Results: All 12 children had regular follow-up within (122.4±25.3)months(range:65 to 163 months). The height and anteroposterior width of the cervical vertebral bodies were similar to these results with those in published reports of growth in normal children of the same age(all P<0.01). At the last follow-up,atlantoaxial fusion of 11 cases had substantial growth (vertical growth rate of the fusion mass:11 cases ≥10%, 1 case <10%);the range of motion in cervical spine was close to the normal level (flexion(55.2±5.0)°,extension (65.3±4.9)°,left bending (41.7±4.5)°,right bending (42.4±4.4)°,left rotation (66.4±5.6)°,right rotation (68.5±5.8)°). Conclusions: Atlantoaxial fusion surgery is satisfactory in the treatment of pediatric atlantoaxial dislocation.During the follow-up,the growth and development of the cervical spine is close to that of normal children of the same age.In long-term observation,it has been found that the operation has no negative effect on the growth and development of the children's cervical spine.

Correlation between treatment effects on response rate and progression-free survival and overall survival in trials of targeted therapies in molecularly enriched populations.

BACKGROUND: The number of randomized trials of agents targeting oncogene-addicted tumors has surged in the past 10 years. Using a meta-analysis, we explored whether improvements in objective response rate (ORR) in comparative trials using targeted agents could serve as a potential surrogate endpoint for improvements in progression-free survival (PFS) or overall survival (OS) in populations with oncogene-addicted cancer. PATIENTS AND METHODS: Using commercial text mining software I2E, we searched ClinicalTrials.gov and MEDLINE databases for randomized, phase III trials based on prospectively defined criteria, including (i) use of agents targeting EGFR activating mutations, ALK rearrangements, BRAF V600E or V600K mutations, and BCR-ABL fusion protein; (ii) molecularly enriched trial population or subpopulation; (iii) control arm only randomized to chemo/cytotoxic therapy. Correlative analyses were performed using ORR, OS, and PFS data from trials that met these criteria. RESULTS: A total of 62 trials were identified; 15 met all of the prespecified criteria. The ORR effect size (both the difference in ORR between arms and the log odds ratio) and log PFS hazard ratio were strongly correlated: -0.78 (P = 0.0007) for the ORR difference model; -0.74 (P = 0.0017) for the log odds ratio model. ORR effect size was positively correlated with the log OS hazard ratio, but more weakly: -0.67 (P = 0.013) for the ORR difference model and -0.58 (P = 0.036) for the log odds ratio model. Analysis of the treatment effects between OS and PFS found no correlation. CONCLUSIONS: These analyses identified a strong correlation between treatment effects on ORR and PFS in randomized clinical trials investigating agents targeting oncogene-driven cancers. A weaker correlation was observed between ORR and OS. These meta-analysis results support the use of a high ORR forming the basis of an initial regulatory approval in biomarker-driven studies.

A basophil-neuronal axis promotes itch.

Itch is an evolutionarily conserved sensation that facilitates expulsion of pathogens and noxious stimuli from the skin. However, in organ failure, cancer, and chronic inflammatory disorders such as atopic dermatitis (AD), itch becomes chronic, intractable, and debilitating. In addition to chronic itch, patients often experience intense acute itch exacerbations. Recent discoveries have unearthed the neuroimmune circuitry of itch, leading to the development of anti-itch treatments. However, mechanisms underlying acute itch exacerbations remain overlooked. Herein, we identify that a large proportion of patients with AD harbor allergen-specific immunoglobulin E (IgE) and exhibit a propensity for acute itch flares. In mice, while allergen-provoked acute itch is mediated by the mast cell-histamine axis in steady state, AD-associated inflammation renders this pathway dispensable. Instead, a previously unrecognized basophil-leukotriene (LT) axis emerges as critical for acute itch flares. By probing fundamental itch mechanisms, our study highlights a basophil-neuronal circuit that may underlie a variety of neuroimmune processes.

Molecular Targeting of H/MDM-2 Oncoprotein in Human Colon Cancer Cells and Stem-like Colonic Epithelial-derived Progenitor Cells.

BACKGROUND/AIM: We have tested whether the anticancer peptide, PNC-27, that kills cancer cells but not normal cells by binding to cancer cell membrane HDM-2 forming pores, kills CD44+ colon cancer stem cells. MATERIALS AND METHODS: Flow cytometry determined the CD44 and HDM-2 expression on six-colon cancer cell lines and one normal cell line (CCD-18Co). MTT, LDH release, annexin V binding and caspase 3 assays were used to assess PNC-27-induced cell death. Bioluminescence imaging measured PNC-27 effects on in vivo tumor growth. RESULTS: High percentages of cells in all six tumor lines expressed CD44. PNC-27 co-localized with membrane HDM-2 only in the cancer cells and caused total cell death (tumor cell necrosis, high LDH release, negative annexin V and caspase 3). In vivo, PNC-27 caused necrosis of tumor nodules but not of normal tissue. CONCLUSION: PNC-27 selectively kills colon cancer stem cells by binding of this peptide to membrane H/MDM-2.

[Risk factors and prognosis of bronchopulmonary dysplasia associated pulmonary hypertension in preterm infants].

Objective: To analyze clinical features, prognosis and risk factors of bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH). Methods: Clinical data of 338 infants with BPD were collected from the neonatal intensive care unit (NICU) in Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University between January 2016 and December 2018. These infants were divided into PH group and non-PH group. The clinical features and prognosis were compared between these two groups by Chi-square test or nonparametric test. Risk factors for BPD-PH were analyzed with binary logistic regression model. Results: Among the 338 BPD infants, 314 had no PH (92.9%) and 24 had PH (7.1%), with an average gestational age of (27.1±1.8) weeks, and 206 were males and 132 females.PH infants had younger gestational age ((26.4±2.1) vs. (27.2±1.7) weeks, t=2.201, P=0.028) and lower birth weight ((798±255) vs. (1 003±240) g, t=4.030, P<0.01), compared to non-PH infants. Besides, duration of mechanical ventilation and non-invasive positive pressure ventilation were higher in PH group than that in non-PH group (14.3 (2.1, 43.7) vs. 0.5 (0, 4.7) d, Z=-4.553, P<0.01; 30.0 (22.5, 64.2) vs. 15.0 (7.0, 26.0) d, Z=-4.838, P<0.01). The proportions of maternal hypertension, small for gestational age (SGA), late onset sepsis, ventilator associated pneumonia, hemodynamically significant patent ductus arteriosus (hsPDA), patent ductus arteriosus (PDA) requiring ligation, severe BPD and severe extrauterine growth retardation (EUGR) were higher in PH group than those in non-PH group ((20.8% (5/24) vs. 6.4% (20/314), 33.3% (8/24) vs. 7.6% (24/314), 54.2% (13/24) vs. 7.3% (23/314), 25.0% (6/24) vs. 6.1% (19/314), 75.0% (18/24) vs. 39.2% (123/314), 45.8% (11/24) vs. 1.9% (6/314), 66.7% (16/24) vs. 7.3% (23/314), 75.0% (18/24) vs. 45.5% (143/314), all P<0.05). Multivariate logistic regression analysis showed that maternal hypertension (OR=12.950, 95%CI: 1.740-96.385), severe bronchopulmonary dysplasia (OR=10.160, 95%CI: 2.725-37.884), SGA (OR=4.992, 95%CI: 1.432-16.920), PDA requiring ligation (OR=19.802, 95%CI: 3.297-118.921), severe EUGR (OR=20.316, 95%CI: 2.221-185.853) were independent risk factors of BPD associated PH. In the 24 infants with PH, all 7 mild PH infants and 8 moderate PH infants survived, while 4 out of 9 severe PH infants died. Among the survivors, the longest duration of oxygen therapy was up to the corrected gestational age of 1 year and 2 months. Conclusions: PH is a severe complication of BPD, and associated with higher mortality and poor prognosis. Echocardiography screening and regular post-discharge follow up are recommended for BPD infants with risk factors of PH.

Collectively stabilizing and orienting posterior migratory forces disperses cell clusters in vivo.

Individual cells detach from cohesive ensembles during development and can inappropriately separate in disease. Although much is known about how cells separate from epithelia, it remains unclear how cells disperse from clusters lacking apical-basal polarity, a hallmark of advanced epithelial cancers. Here, using live imaging of the developmental migration program of Drosophila primordial germ cells (PGCs), we show that cluster dispersal is accomplished by stabilizing and orienting migratory forces. PGCs utilize a G protein coupled receptor (GPCR), Tre1, to guide front-back migratory polarity radially from the cluster toward the endoderm. Posteriorly positioned myosin-dependent contractile forces pull on cell-cell contacts until cells release. Tre1 mutant cells migrate randomly with transient enrichment of the force machinery but fail to separate, indicating a temporal contractile force threshold for detachment. E-cadherin is retained on the cell surface during cell separation and augmenting cell-cell adhesion does not impede detachment. Notably, coordinated migration improves cluster dispersal efficiency by stabilizing cell-cell interfaces and facilitating symmetric pulling. We demonstrate that guidance of inherent migratory forces is sufficient to disperse cell clusters under physiological settings and present a paradigm for how such events could occur across development and disease.

Management of colorectal anastomotic stricture with multidiameter balloon dilation: long-term results.

BACKGROUND: Postoperative colorectal anastomotic strictures are quite common. As such, many techniques have been available to address such a problem, one of which is endoscopic dilation. The aim of the present study was to evaluate the long-term outcomes following endoscopic dilation using a multidiameter balloon. METHODS: A retrospective study was conducted on patients with postoperative anastomotic stenosis treated with endoscopic dilation using a multidiameter balloon at our institution, in January 2005-December 2019 were retrospectively reviewed, excluding those with tumor recurrence. Perioperative factors, complications, and recurrence rates were analyzed. RESULTS: There were 40 patients, (22 males and 18 females, mean age 64.6 ± 10.7 years, range 33-84 years). The median follow-up period was 56 months (interquartile range 22.5-99 months). Only 1 complication occurred, micro-perforation due to guided wire injury, which was managed conservatively. Five (12.5%) patients developed restenosis and underwent repeat balloon dilation. None of the five recurrences required more aggressive management, such as redo anastomosis. CONCLUSIONS: Endoscopic multidiameter balloon dilation is a safe and effective method for treating benign colorectal anastomotic strictures.

Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis.

Atopic dermatitis (AD) is a widespread, chronic skin disease associated with aberrant allergic inflammation. Current treatments involve either broad or targeted immunosuppression strategies. However, enhancing the immune system to control disease remains untested. We demonstrate that patients with AD harbor a blood natural killer (NK) cell deficiency that both has diagnostic value and improves with therapy. Multidimensional protein and RNA profiling revealed subset-level changes associated with enhanced NK cell death. Murine NK cell deficiency was associated with enhanced type 2 inflammation in the skin, suggesting that NK cells play a critical immunoregulatory role in this context. On the basis of these findings, we used an NK cell-boosting interleukin-15 (IL-15) superagonist and observed marked improvement in AD-like disease in mice. These findings reveal a previously unrecognized application of IL-15 superagonism, currently in development for cancer immunotherapy, as an immunotherapeutic strategy for AD.

Age distribution of human papillomavirus infection and neutralizing antibodies in healthy Chinese women aged 18-45 years enrolled in a clinical trial.

OBJECTIVES: Data from clinical trials of human papillomavirus (HPV) vaccines showed that women naïve (negative for both type-specific antibodies and DNA) to vaccine types would derive benefit from vaccination; therefore, an understanding of the proportion of naïve women in different age groups is important for developing HPV vaccination strategies. METHODS: From November 2012 to April 2013, a total of 7372 healthy women aged 18-45 years were recruited in five provinces in China. Cervical specimens and serum samples were collected for each woman at entry. Cervical specimens were first tested by the HPV DNA enzyme immunoassay method; if positive, the specimens were then tested by reverse hybridization line probe assay and HPV-16 and HPV-18 specific polymerase chain reactions. Neutralizing antibodies against HPV-16 or HPV-18 were tested with a pseudovirion-based neutralization assay. RESULTS: The overall prevalence of high-risk HPV DNA was 14.8% (1088/7367, 95% CI 14.0-15.6), and the seroprevalence of neutralizing antibodies against HPV-16 and HPV-18 was 12.6% (925/7367) and 4.9% (364/7367), respectively. In younger women (18-26 years) and middle-aged women (27-45 years), 83.8% (3116/3719) and 81.4% (2968/3648) were naïve to both HPV-16 and HPV-18 (both neutralizing antibodies and DNA were negative), respectively. In addition, 98.5% (3664/3719) and 98.0% (3575/3648) of the younger or middle-aged women were naïve to at least one HPV type (HPV-16 or HPV-18). DISCUSSION: This study revealed that the majority of Chinese women aged 18-26 years and 27-45 years were naïve to both HPV-16 and HPV-18 and would thus derive full benefit from bivalent HPV vaccination.

Correlation between miR-1207-5p expression with steroid-induced necrosis of femoral head and VEGF expression.

OBJECTIVE: The aim of this study was to investigate the expression level of micro-ribonucleic acid-1207-5p (miR-1207-5p) in steroid-induced necrosis of femoral head (SNFH) and its correlation with SNFH. Meanwhile, we also aimed to analyze the relationship between miR-1207-5p expression and vascular endothelial growth factor (VEGF) in the femoral head. PATIENTS AND METHODS: From May 2016 to December 2017, 60 patients aged (55.4±8.7) were selected in our hospital. All patients were diagnosed and confirmed as SNFH. Total RNA was extracted from the necrotic femoral head tissues and peripheral blood. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to detect the expression level of miR-1207-5p in tissues. At the same time, immunohistochemistry and Western blotting were adopted to detect VEGF expression in the bone tissue of patients with high or low expression of miR-1207-5p. 7 patients with femoral neck fracture aged (45.6±4.51) were enrolled in the control group. In the animal experiment, the rat SNFH model was established by intraperitoneal injection of lipopolysaccharide and methylprednisolone. Subsequently, the expression levels of miR-1207-5p and VEGF in necrotic femoral tissues were detected. Meanwhile, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was applied to detect cell apoptosis in bone lacunae of miR-1207-5p high expression group and miR-1207-5p low expression group, respectively. RESULTS: The expression level of miR-1207-5p in the necrotic bone tissue of the SNFH group was significantly higher than that of the control group. The expression level of miR-1207-5p was inversely proportional to Harris Hip score (p<0.05). A higher expression of miR-1207-5p indicated a lower expression level of VEGF (p<0.05). The animal experimental results revealed that miR-1207-5p expression in the necrotic femoral head tissue of SNFH group was significantly higher than that of the control group. Furthermore, the number of apoptotic cells in bone lacunae was remarkably higher in miR-1207-5p high expression group (p<0.05). CONCLUSIONS: MiR-1207-5p is significantly up-regulated in necrotic femoral head tissue and serum of SNFH patients. Meanwhile, its expression level is inversely proportional to Harris Hip score of patients. The possible underlying mechanism may be related to the inhibitory effect of miR-1207-5p on VEGF.

[Children's non-carcinogenic health risk assessment of heavy metals exposure to residential indoor dust around an e-waste dismantling area in South China].

Objective: To evaluate the non-carcinogenic health risk of heavy metals (As, Cd, Cr, Cu, Mn, Pb and Zn) in residential indoor dust for young children around an e-waste dismantling area in South China. Methods: A village around an e-waste dismantling area in South China was selected as a research site in October 2016. Convenience sampling method was used to select 36 houses in the village and 36 dust samples were collected by vacuum cleaner. The concentrations of heavy metals (Cd, Cr, Cu, Mn, Pb and Zn) in each sample were determined and expressed by the average value. Non-carcinogenic health risk assessment was conducted using the US Environmental Protection Agency (EPA) Health Risk Assessment (HRA) model, the American Toxicology and Disease Registry (ATSDR) Target-organ Toxicity Dose (TTD) approach and the ATSDR Binary Weight-of-Evidence (BINWOE) model. Results: The mean ± SD of concentrations of As, Cd, Cr, Cu, Mn, Pb and Zn were (48.90±33.91), (5.95±3.89), (173.57±580.37), (412.71±1 190.00), (612.82±540.70), (297.41±293.22) and (1 052.81±1 156.48) mg/kg, respectively. The HI value of TTD (2.670) and BINWOE (2.933) were higher than the safety threshold of EPA recommended non-carcinogenic health risk. The HI value of TTD and BINWOE were 1.93 and 2.12 times higher than the HI value of HRA (1.386). Conclusion: There was non-carcinogenic health risk of heavy metals (As, Cd, Cr, Cu, Mn, Pb and Zn) via residential indoor dust around the e-waste dismantling area for local children.

Correction: Toosendanin demonstrates promising antitumor efficacy in osteosarcoma by targeting STAT3.

Since the publication of this paper, the authors have noticed that the article contains an error in Figure 3e (TSN, 50 nM). As a result of the misfiling of the data, the incorrect image was inadvertently inserted in Figure 3e during figure preparation. The corrected image is shown in this correction.

A novel therapy, using Ghrelin with pegylated G-CSF, inhibits brain hemorrhage from ionizing radiation or combined radiation injury.

Medical treatment becomes challenging when complicated injuries arise from secondary reactive metabolic and inflammatory products induced by initial acute ionizing radiation injury (RI) or when combined with subsequent trauma insult(s) (CI). With such detrimental effects on many organs, CI exacerbates the severity of primary injuries and decreases survival. Previously, in a novel study, we reported that ghrelin therapy significantly improved survival after CI. This study aimed to investigate whether brain hemorrhage induced by RI and CI could be inhibited by ghrelin therapy with pegylated G-CSF (i.e., Neulasta®, an FDA-approved drug). B6D2F1 female mice were exposed to 9.5 Gy 60Co-γ-radiation followed by 15% total-skin surface wound. Several endpoints were measured at several days. Brain hemorrhage and platelet depletion were observed in RI and CI mice. Brain hemorrhage severity was significantly higher in CI mice than in RI mice. Ghrelin therapy with pegylated G-CSF reduced the severity in brains of both RI and CI mice. RI and CI did not alter PARP and NF-κB but did significantly reduce PGC-1α and ghrelin receptors; the therapy, however, was able to partially recover ghrelin receptors. RI and CI significantly increased IL-6, KC, Eotaxin, G-CSF, MIP-2, MCP-1, MIP-1α, but significantly decreased IL-2, IL-9, IL-10, MIG, IFN-γ, and PDGF-bb; the therapy inhibited these changes. RI and CI significantly reduced platelet numbers, cellular ATP levels, NRF1/2, and AKT phosphorylation. The therapy significantly mitigated these CI-induced changes and reduced p53-mdm2 mediated caspase-3 activation. Our data are the first to support the view that Ghrelin therapy with pegylated G-CSF is potentially a novel therapy for treating brain hemorrhage after RI and CI.