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Xiaohua Liang,1 Shengqiang Dang2 1Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China; 2Department of Oncology, Chang’an Hospital of Xi’an, Xi’an, Shaanxi, 710016, People’s Republic of ChinaCorrespondence: Shengqiang DangDepartment of Oncology, Chang’an Hospital of Xi’an, 17 Wenjing Road, Xi’an, Shaanxi, 710016, People’s Republic of ChinaEmail sqdangcah@163.comPurpose: This study aimed to evaluate the associations between mitochondrial dynamics related genes -MFN1, MFN2 and DRP1 polymorphisms and risk of lung cancer.Methods: Six polymorphisms of MFN1, MFN2 and DRP1 were genotyped in 600 cases and 600 controls using a MassARRAY platform.Results: The MFN1 rs13098637-C and DRP1 rs879255689-A alleles were associated with an increased risk of lung cancer (prs13098637=0.004, prs879255689=0.005), while MFN2 rs4240897-A and rs2236058-G were related to a decreased risk of disease (p< 0.001). The rs13098637-TC/CC and rs879255689-GA/AA were determined as risk genotypes for lung cancer (prs13098637=0.014, prs879255689=0.013), whereas the rs4240897-GA/AA and rs2236058-GG were identified as protective genotypes against lung cancer risk (p< 0.001). Genetic model analysis showed that rs13098637 was correlated with an elevated risk of lung cancer in dominant and log-additive models (pdominant=0.007, plog-additive=0.004). Moreover, rs879255689 was associated with an increased risk of disease in all three models (pdominant=0.014, precessive=0.028, plog-additive=0.005). In contrast, rs4240897 and rs2236058 were related to reduced risk of disease in all three models (rs4240897: pall< 0.001; rs2236058: pdominant=0.008, precessive< 0.001, plog-additive< 0.001). In addition, these associations were related to the smoking status and pathological type of lung cancer patients.Conclusion: These results shed new light on the association between mitochondrial dynamics related genes and risk of lung cancer.Keywords: lung cancer, gene polymorphisms, mitochondrial dynamics, MFN1, MFN2

Background Idiopathic central precocious puberty (ICPP) reduces patient health-related quality of life (HRQoL). The impacts of disease and treatment on families are also an important concern. This study aimed to assess the association between family impact and HRQoL of children with ICPP. Methods We conducted a case–control study in Chongqing, China. A case group of 134 children with ICPP aged 5–12 years and their caregivers was recruited from a children’s hospital in Chongqing. A total of 210 gender- and age-matched subjects from two primary schools were selected as controls. PedsQLTM4.0 Generic Core Scales (GCS) and PedsQL™ Family Impact Module (FIM) were used in this study. Results Children with ICPP scored lower than controls in all HRQoL domains except physical functioning. In particular, the two groups were significantly different in emotional functioning scores (d = 0.414, P d = 0.288–1.030, all P P Conclusions Children with ICPP demonstrated lower quality of life and greater family impact compared to healthy controls. In addition, less impact of disease on parent HRQoL and family functioning was associated with better HRQoL of ICPP patients, patients aged older, treated with drug combination, cared by employed or well-educated caregivers reported better HRQoL. Health care professionals should pay more attention to younger patients treated with GnRHa alone, and provide targeted interventions for caregivers depending on their demographic background to reduce family impact and thereby improve patient HRQoL.

BACKGROUND Coronavirus disease 2019 (COVID-19) is an emerging, rapidly evolving disease that spreads through the respiratory system and is highly contagious. In March 2020, the World Health Organization declared the COVID-19 outbreak a pandemic. In China, the pandemic was controlled after 2 mo through effective policies and containment measures. Describing the detailed policies and containment measures used to control the epidemic in Chongqing will provide a reference for the prevention and control of COVID-19 in other areas of the world. AIM To explore the effects of different policies and containment measures on the control of the COVID-19 epidemic in Chongqing. METHODS Epidemiological data on COVID-19 in Chongqing were prospectively collected from January 21 to March 15, 2020. The policies and prevention measures implemented by the government during the epidemic period were also collected. Trend analysis was performed to explore the impact of the main policy measures on the effectiveness of the control of COVID-19 in Chongqing. RESULTS As of March 15, the cumulative incidence of COVID-19 in Chongqing was 1.84/100000 (576 cases) and the infection fatality rate was 1.04% (6/576). The spread of COVID-19 was controlled by effective policies that involved establishing a group for directing the COVID-19 epidemic control effort; strengthening guidance and supervision; ensuring the supply of daily necessities and medical supplies and equipment to residents; setting up designated hospitals; implementing legal measures; and enhancing health education. Medical techniques were implemented to improve the recovery rate and control the epidemic. Policies such as "the lockdown of Wuhan", "initiating a first-level response to major public health emergencies", and "implementing the closed management of residential communities" significantly curbed the spread of COVID-19. Optimizing the diagnosis process, shortening the diagnosis time, and constructing teams of clinical experts facilitated the provision of "one team of medical experts for each patient" treatment for severe patients, which significantly improved the recovery rate and reduced the infection fatality rate. CONCLUSION The prevention policies and containment measures implemented by the government and medical institutions are highly effective in controlling the spread of the epidemic and increasing the recovery rate of COVID-19 patients.

The prevalence of childhood hypertension is recognized as an important parameter of cardiovascular risk in adults. This retrospective study aimed to ascertain the prevalence and risk factors for hypertension from birth through childhood as of 2014. Stratified cluster sampling was used to select 17,007 participants (5971 with biochemical indexes available) aged 6-12 years on two avenues per region in urban, suburban, and rural areas. The prevalence of hypertension was 12.55%; children with obesity combined with rural residence, low family income, birth weight ( 10 months of breastfeeding had a significantly elevated prevalence of hypertension (37.06%, 30.41%, 30.04%, and 30.84%, respectively). Obesity and heart rate were the significant anthropometric determinants; gestational hypertension, BWP25 and >10 months of breastfeeding were the significant perinatal determinants; rural residence was the significant socioeconomic determinant; fasting blood glucose, triglycerides, and low-density lipoprotein cholesterol were the significant serum biochemical determinants; and red blood cell counts and platelet counts were the significant haematological determinants of childhood hypertension. The adjusted R2 values were 14.45% and 24.88% in the full models excluding and including serum indexes, respectively. We observed a notable prevalence of hypertension in a large paediatric sample. Obesity, high heart rate, BWP25, >10 months of breastfeeding, low family income, rural residence, abnormal lipid metabolism, and abnormal blood counts were associated with an increased risk of hypertension.

Background: Identification of early modifiable factors is crucial to delay or prevent the development of cognitive impairment and reduce the social and economic burden.Objective: This study aimed to examine the longitudinal associations of childhood neighborhood quality (CNQ) with the risk of later-life cognitive dysfunction and the role of body mass index (BMI) in this association.Methods: A total of 8,289 community-dwelling middle-aged and elderly population from wave 2011, wave 2013, and wave 2015 of the China Health and Retirement Longitudinal Study (CHARLS) were included. Cognitive function and CNQ were measured by standardized questionnaires. Multilevel linear regression models were used to estimate the associations of CNQ and cognitive function. The interactions of BMI with CNQ in the progress of cognitive function were also estimated.Results: The participants with higher CNQ had a significantly low risk of cognitive impairment than those with lower CNQ score (β = 0.067, 95% CI: 0.031, 0.103), and the results remained similar (β = 0.039, 95% CI: 0.004, 0.075) after controlling other confounding variables. Furthermore, there was an interaction between BMI with CNQ score (P < 0.001) for the risk of cognitive impairment. In BMI-stratified analysis, we found that the association of CNQ and cognitive function was not statistically significant in overweight or obese population (β = 0.019, 95% CI: −0.032, 0.070), but was statistically significant in people with lower BMI (β = 0.059, 95% CI: 0.010, 0.107).Conclusions: Higher CNQ score is significantly associated with the lower risk of cognitive dysfunction in adulthood. BMI may moderate the associations of CNQ with the risk of cognitive function.

Background The prevalence of obesity and overweight in childhood has increased dramatically over the past decades globally. Thus, the risk factors of overweight and obesity in children and adolescents must be studied. Objectives This study aimed to reveal the prevalence of childhood obesity and examine the relationship between socioeconomic status (SES) and z-body mass index (z-BMI) via parental obesity and dietary intake using path analysis. Methods Stratified cluster sampling was used to select 17,007 participants aged 6–12 years on two avenues per region in urban, suburban, and rural areas. Path analysis was conducted to examine the mediators between SES and z-BMI. Results The prevalence rates of overweight and obesity were 13.36% and 8.60%, respectively, and were positively correlated with the father’s education level, family income, a birth weight > 3000g, a parental obesity history, vegetable intake and red meat intake (all P < 0.05). Four mediators (paternal obesity history, red meat intake, vegetable intake, and nutritional supplements) were observed, and the four path analyses were significant (all P < 0.05). The adjusted total effects on z-BMI were significant for income (βTot = 0.03; P < 0.01), father’s education (βTot = 0.05; P < 0.001), and region (βTot = 0.11; P Conclusions The prevalence of overweight/obesity in children was notable, and the relationship between SES and z-BMI was mediated by paternal obesity history and dietary intake.

Background Growing evidence indicates that high phosphoserine phosphatase (PSPH) expression is associated with tumor prognosis in many types of cancers. However, the role of PSPH in non-small cell lung cancer (NSCLC) is unclear. The purpose of this study was to investigate the clinical significance of PSPH in NSCLC. Methods One hundred forty-three patients with histologically confirmed NSCLC who underwent surgery were included. Quantitative real-time PCR and Western blot were used to assess PSPH expression in paired tumor and corresponding adjacent non-tumorous tissues. The role of PSPH in invasion and cell growth was investigated in vitro. Results Compared to adjacent normal lung tissues, PSPH messenger RNA and protein levels were significantly higher in NSCLC tissues, and the PSPH expression level was positively related to clinical stage, metastasis, and recurrence. High PSPH expression was predictive of poor overall survival. A549 cells transfected with small interfering-PSPH showed inhibited cell migration, invasion, and proliferation. We further demonstrated that PSPH might promote the invasive capabilities of NSCLC cells through the AKT/AMPK signaling pathway. Conclusion Our results indicate that PSPH may act as a putative oncogene in NSCLC, and may be a vital molecular marker for the metastasis and proliferation of NSCLC cells by regulating the AKT/AMPK signaling pathway.

Objective: Increased arterial stiffness measured by pulse wave velocity (PWV) has been shown to be an important parameter of cardiovascular risk. Longitudinal development of PWV from youth to early adulthood and its possible sociodemographic, anthropometric, hemodynamic and behavioral moderators will be illustrated.Methods: Individual growth curves of carotid-distal PWV across age were created for 559 African American and European American men and women with a maximum of five assessments over an average of 7-year follow-up (mean age at participants' first assessment, 22.3 +/- 3.4).Results: African Americans and men had significantly higher PWV than did European Americans and women (PsConclusion: We observed significant ethnic and sex differences in longitudinal trajectories of PWV in youth and young adults. In addition, individual differences in PWV growth can largely be explained by mean arterial pressure, waist, marital status of parents and marijuana use.

Epidermal growth factor receptor (EGFR) mutations are associated with leptomeningeal metastases (LM) of nonsmall cell lung cancer and sensitivity to tyrosine kinase inhibitor (TKI) treatment. Owing to the difficulty of obtaining carcinomatous meningeal tissue for analysis, cerebrospinal fluid (CSF) might be an alternative.To investigate the EGFR mutation detection in the CSF of lung adenocarcinoma patients with LM.Twenty-five lung adenocarcinoma patients with LM diagnosed by CSF cytology were retrospectively evaluated. The results of EGFR mutation detection in CSF, the treatment plan, and clinical outcome information were recorded.Nineteen patients had a known EGFR status in their primary tumors. Twenty patients received EGFR mutation analysis in CSF after LM diagnosis and 14 of them with a known EGFR mutation status of both primary tumors and CSF. Ten (71.4%) had the same EGFR gene status. In primary tumors, no T790M mutations were detected, whereas in CSF, 2 L858R cases and 1 19del case had T790M mutations at the same time. The detection rate of T790M mutations in CSF was 18.1% (2 of 11) in all cases with EGFR-sensitive mutations in the primary lesion.EGFR mutation detection in CSF of lung adenocarcinoma patients with LM might be an alternative when leptomeningeal biopsy cannot be applied and may help to guide TKI treatments.

Background. The prevalence of hypertension in children increases rapidly. This paper is to investigate the association of vitamin A and serum 25(OH)D level with hypertension and to explore the risk factors of hypertension in children. Methods. 164 children (age: 6-12 years, females: 49.39%) were included in this case-control study. The serum vitamin A and serum 25(OH)D level, the transcription level of RARs and RXRs, 25(OH)D receptor, and the retinol acyltransferase (LRAT), an indicator of vitamin A storage function, were measured. Results. The serum vitamin A level in hypertensive subjects was not significantly different compared to control, but the serum 25(OH)D level was significantly lower in hypertensive subjects compared to control (38.22±12.00umol/L vs. 43.28±12.33 umol/L, P=0.02). The transcription levels of RARα, RARβ, and RARγ were not significantly different between the two groups; but the LRAT was lower in the hypertensive group than that in the control (PP=0.003). Logistic regression model showed that LRAT, HDL, and breastfed duration were negatively associated with blood pressure, and waist circumference was positively associated with blood pressure. Conclusions. The LRAT, serum 25(OH)D, and 25(OH)D receptor were significantly associated with blood pressure level, and both breastfed and HDL-C were independent protective factors of blood pressure level in children.

BACKGROUND: To explore the variations of the gross tumor volume (GTV) from different three-dimensional computed tomography (3DCT) scan modes and the consistency of internal target volume (ITV) between different 3DCT, cone-beam computed tomography (CBCT) and four-dimensional computed tomography (4DCT) scan, a study using a motion phantom simulating sinusoidal movement was conducted. METHODS: For three 3DCT scan modes: the GTV was contoured, and ITV(I) was generated on the basis of GTV with a 10-mm margin while ITV(II) and ITV(III) with a 0-mm margin on the motion direction. ITV(CBCT) and ITV(MIP) were contoured on the images of CBCT and maximum-intensity projection (MIP) reconstructed 4DCT images. The centroid position shifts of ITVs were analyzed. The volume consistency between ITV(I), ITV(II), ITV(III) and ITV(MIP) were evaluated by calculating the Dice similarity coefficient (Dsc) and the value of Δ Volume (ΔV). Furthermore, the 3DCT and CBCT images from 12 NSCLC patients were retrospectively collected, then the Dsc and ΔV were calculated. RESULTS: The mean ± standard deviation of centroid position of ITV(I), ITV(II) and ITV(III) were 2.3±4.7, 2.6±4.0, and 1.0±1.4 mm, respectively. The mean ± standard deviation of Dsc between ITV(I), ITV(II), ITV(III) and ITV(MIP) were 0.78±0.77, 0.86±0.1, and 0.94±0.05, respectively. The ΔV of ITV(I), ITV(II), ITV(III) were 29.67%, 17.22%, and 6.46%, respectively. The ITV from CBCT showed a deduction rate of 3.1–9.3% compared to 4DCT. For the patients, the mean Dsc andΔV between ITV(I) and ITV(CBCT) were 0.50 and 60.76%. CONCLUSIONS: The GTV acquired from 3DCT scan mode I possessed great deviation of centroid position and target volume. ITV on the basis of this GTV was significantly larger than ITV(MIP). A good similarity was showed between ITV(III) and ITV(MIP), 4DCT is still a golden standard for the ITV delineation, but in the absence of 4DCT, image from 3DCT scan mode III and KV-CBCT may be considered for ITV delineation with caution.

Vitamin A (VA) deficiency triggers many diseases and is a worldwide nutrition problem. The Retinol acyltransferase (LRAT) is an indicator of VA storage function, and the relationship between LRAT and blood pressure level and the regulation mechanism will be elucidated.160 children aged 6-12 years were included, and the serum VA and, the transcription levels of LRAT and RARs, were measured. Spontaneously hypertensive rats (SHRs) and WKY rats were treated with VA deficiency (VAD) or normal (VAN) fodder for 20 weeks. LRAT, retinoic acid, renin angiotensin system (RAS) biomarkers, and the structure and function of the heart for SHRs were measured.The serum retinol and serum retinol/BMI levels were lower in children in the low LRAT group (LRATPLRAT may be an important biomarker of vitamin A deficiency in target organs and may regulate BP by affecting RAS biomarkers.

Background An increased prevalence of adolescent metabolic syndrome (MS) is associated with adulthood cardiovascular diseases. This study aimed to explore the potential relationship of quality of life (QoL) and personality traits with adolescent MS. Methods A total of 1961 participants from Chongqing with an average age of 11.68 years old from a cohort study established in 2014 and followed up through 2019 were included. QoL information, Eysenck’s personality questionnaire and MS components were collected. Results A higher QoL domain score of physical activity ability (PAA) was a protective factor for both MS and MS score (all P P P = 0.04) and MS score (P P ≤ 0.01). Conclusions QoL score and extraversion personality score were independent protective factors against both MS prevalence and MS score, suggesting that community intervention to improve the QoL and psychological health of children are essential.

Background. Increasing evidence has revealed that mesenchymal stromal cell (MSC) transplantation alleviates hypoxic-ischemic brain damage (HIBD) induced neurological impairments via immunomodulating astrocyte antiapoptosis effects. However, it remains unclear whether MSCs regulate neuron autophagy following HIBD. Results. In the present study, MSC transplantation effectively ameliorated learning-memory function and suppressed stress-induced hippocampal neuron autophagy in HIBD rats. Moreover, the suppressive effects of MSCs on autophagy were significantly weakened following endogenous IL-6 silencing in MSCs. Suppressing IL-6 expression also significantly increased p-AMPK protein expression and decreased p-mTOR protein expression in injured hippocampal neurons. Conclusion. Endogenous IL-6 in MSCs may reduce autophagy in hippocampal neurons partly through the AMPK/mTOR pathway.

International audience; Background: Chinese blood donors with unconfirmed serological and/or molecular screening results are deferred permanently. This study investigated the implementation and performance of a follow-up program aiming to improve the notification and management of deferred donors in Dalian, China.Study design and methods: From January 2013 to February 2018, 411,216 donations were tested for HBsAg, anti-HCV, anti-HIV/HIV antigen, and antibodies to Treponema pallidum. HBV, HCV, and HIV nucleic acid testing (NAT) was performed in mini-pools of six or in individual donations (IDs). Reactive donations were evaluated further with alternative serological assays and ID-NAT re-testing. A follow-up procedure was developed to evaluate a subset of deferred donors that were either potential NAT yield cases, serology non-reactive and NAT non-repeated reactive (NRR), or serology NRR irrespective of NAT result.Results: Serological and molecular routine, plus supplemental testing, identified HBV, HCV, HIV, and TP in 503 (0.12%), 392 (0.09%), 156 (0.04%), and 2041 (0.49%) donations, respectively. Overall, 683 of 4156 (16.4%) eligible donors and 205 donors deferred prior 2013 participated in the program. They included 664 serology NRR and 224 NAT yield cases, and 58.8% repeat donors. All markers combined, follow-up documented false reactivity, primary acute infections, and OBI in 61.9% (550/888), 3.3% (29/888), and 12.8% (114/888) of these donors, respectively. Isolated anti-HBc or anti-HBs reactivity was observed in 22% of cases.Conclusion: Follow-up testing refined infection status in 78.0% (693/888) of deferred donors with unconfirmed screening results. This high false-positive rate encouraged to reevaluate the current screening strategies and to consider donor reentry.

Objective. The increased blood pressure level in children and adolescents is recognized as an essential predictor of adulthood cardiovascular disease. This study aimed to ascertain the prevalence and the urban-rural disparity of childhood hypertension in the southwest of China. Methods. Using stratified cluster sampling in urban and rural areas, a total of 13597 primary school children aged 6∼12 years living in the Southwest of China were included. The prevalence of hypertension was analyzed. The risk factors were collected by questionnaires, and the risk factors of childhood hypertension were analyzed by the logistic regression model. Results. The prevalence of hypertension was 13.75%, 9.02%, and 17.47% in total, urban, and rural children, respectively, and the urban-rural difference was 8.44% (95%CI: 7.32%, 9.56%). Children with obesity, maternal gestational hypertension, >10 months of breastfeeding, or low family income had a significantly increased prevalence of hypertension (29.4%, 20.00%, 16.31%, and 16.25%, respectively). Rural residence, intake of more pickle (in rural), maternal gestational hypertension (in urban), low birth weight (in rural), obesity, increased heart rate, and red blood cell counts were the risk factors of childhood hypertension. The adjusted R2 values were 13.61%, 23.25%, 10.88%, 11.12%, 12.23%, and 25.04% in the full models excluding and including serum indexes for total, urban, and rural children, respectively. Conclusions. The prevalence of childhood hypertension is significant in the Southwest of China and alarming in rural areas, which requires community intervention. Children living in rural areas combined with obesity, low social economic status, dietary imbalance, and abnormal lipid metabolism were associated with an increased risk of hypertension, and routine care programs should be conducted to prevent childhood hypertension.

Background: Currently, the treatment of symptomatic brain metastases from lung adenocarcinoma has remained difficult. Bevacizumab combined with chemotherapy is one of the standard treatments of lung adenocarcinoma. This study was designed to investigate the efficacy and safety of bevacizumab combined with chemotherapy in symptomatic brain metastases from lung adenocarcinoma that are not suitable for local treatments, and to explore the predictive value of baseline serum vascular endothelial growth factor (VEGF) for the treatment. Methods: We retrospectively reviewed 14 consecutive patients, between Jan 2015 and Jul 2017, with brain metastases from lung adenocarcinoma who received bevacizumab and chemotherapy to determine efficacy and toxicity. Kaplan-Meier method was used to estimate survival curves, and univariate and multivariate analyses were performed by Cox proportional hazard model. The primary endpoints were objective response rate (ORR) and intracranial ORR (iORR). The secondary endpoints were progression-free survival (PFS), intracranial PFS (iPFS), overall survival (OS) and disease control rate (DCR). Results: The efficacy of 12 patient was evaluated. Overall ORR was 25% (3/12) and the iORR of brain lesions was 33.3% (4/12). DCR was 75% (9/12). The median OS was 18.3 months, the median PFS was 6.7 months, and the median iPFS was 12 months. After 2 cycles of bevacizumab, 10 patients showed improved symptoms of central nervous system (CNS), and the symptom control rate was 83.3% (10/12). Head MRI showed that edema in the brain was greatly reduced in 6 patients, resulting in the lessened usage of dexamethasone. iPFS was significantly shorter in high VEGF group (3.6 vs . 8.0 m, P=0.02), and multivariate analysis showed a significant correlation between iPFS and serum baseline VEGF level (P=0.023). The most commonly adverse events of bevacizumab included leukopenia [5 (35.7%)], fatigue [3 (21.4%)], thrombocytopenia [3 (21.4%)], anemia [2 (14.3%)], which were mostly degree I and II. Conclusions: This study showed bevacizumab combined with chemotherapy could effectively control intracranial lesions, relieve symptoms, and improve the quality of life and survival of patients with brain metastases from lung adenocarcinoma. Serum baseline VEGF may be a predictor of efficacy of bevacizumab plus chemotherapy in the treatment of brain metastases from lung adenocarcinoma.

Background Brain metastases (BM) from non-small cell lung cancer (NSCLC) are the most frequent intracranial tumors. To identify patients who might benefit from intracranial surgery, we compared the six existing prognostic indexes(PIs) and built a nomogram to predict the survival for NSCLC with BM before they intended to receive total intracranial resection in China. Methods First, clinical data of NSCLC presenting with BM were retrospectively reviewed. All of the patients had received total intracranial resection and were randomly distributed to developing cohort and validation cohort by 2:1. Second, we stratified the cohort using a recursive partitioning analysis(RPA), a score index for radiosurgery (SIR), a basic score for BM (BS-BM), a Golden Grading System (GGS), a disease-specific graded prognostic assessment (DS-GPA) and by NSCLC-RADES. The predictive power of the six PIs was assessed using the Kaplan–Meier method and the log-rank test. Third, univariate and multivariate analysis were explored, and the nomogram predicting survival of BMs from NSCLC was constructed using R 3.2.3 software. The concordance index (C-index) was calculated to evaluate the discriminatory power of the nomogram in the developing cohort and validation cohort. Results BS-BM could better predict survival of patients before intracranial surgery compared with other PIs. In the final multivariate analysis, KPS at diagnosis of BM, metachronous or synchronous BM and the histology of lung cancer appeared to be the independent prognostic predictors for survival. The C-index in the developing cohort and validation cohort were 0.75 and 0.71 respectively, which was better than the C-index of the other six PIs. Conclusions The new nomogram is a promising tool in further choosing the candidates for intracranial surgery among NSCLC with BM and in helping physicians tailor suitable treatment options before operation in clinical practice.

Protein O-fucosylation is an important glycosylation modification and plays an important role in embryonic development. Protein O-fucosyltransferase 1 (poFUT1) is an essential enzyme that catalyzes the synthesis of protein O-fucosylation. Our previous studies showed that poFUT1 promoted trophoblast cell migration and invasion at the fetal-maternal interface, but the role of poFUT1 in trophoblast cells proliferation remains unclear. Here, immunohistochemistry data showed that poFUT1 and PCNA levels were decreased in abortion patient's trophoblasts compared with women with normal pregnancies. Our results also showed that poFUT1 promoted trophoblast cell proliferation by CCK-8 assay and cell cycle analysis. PoFUT1 increased the phosphorylation of ERK1/2, p38 MAPK, and PI3K/Akt, while inhibitors of ERK1/2(PD98059), p38 MAPK(SB203580), and PI3K (LY294002) prevented ERK1/2, p38 MAPK, and Akt phosphorylation. Moreover, poFUT1 stimulation of trophoblast cells proliferation correlated with increased cell cycle progression by promoting cells into S-phase. The underlying mechanism involved increased cyclin D1, cyclin E, CDK 2, CDK 4, and pRb expression and decreased levels of the cyclin-dependent kinase inhibitors p21 and p27, which were blocked by inhibitors of the upstream signaling molecules MAPK and PI3K/Akt. In conclusion, poFUT1 promotes trophoblast cell proliferation by activating MAPK and PI3K/Akt signaling pathways.

Since the establishment of People's Republic of China in 1949, the Chinese government has encountered several catastrophes related to transfusion transmitted diseases. The government's increasing attention to blood safety has prompted the initiation of a series of policies and measures that have enhanced the level of safety for the blood supply and met the basic clinical demands of blood for 1.3 billion people in the country. Blood donation screening strategies in China predominantly comprise donor screening and donor testing. Donor screening includes selection of low-risk blood donors by the use of a donor history questionnaire, predonation physical examination, and initial rapid donor testing. Donor testing includes direct pathogen detection and serology tests. The year 1998 marked the most transformative change in blood donor selection and screening policies in China. Before 1998, paid donation was the predominant mode of blood donation. Donor screening and donor testing were conducted before donation, and only those who were eligible were allowed to donate. To ensure the safety of blood, donor testing was performed again after donation. After the implementation of the Blood Donation Law in 1998, to promote voluntary and unpaid donation, predonation donor testing was eliminated to reduce the amount of waiting time and to provide a more convenient donation experience for blood donors. However, it is the national requirement that donated blood should undergo 2 rounds of testing using different equipment or reagents, conducted by different personnel. Donor selection has transitioned from paid donation and obligatory donation to voluntary donation with fixed volunteer groups, as the latter mode of donation provides the lowest risks. Donations are currently screened for syphilis, hepatitis C virus, HIV, and hepatitis B virus (HBV). Units, previously typed only for ABO, are now routinely tested for both ABO and Rh(D). Innovations in testing technologies and methods have also brought changes to screening parameters. For instance, screening for HBV pathogens evolved from the early use of hemagglutination method to the later use of radioimmunoassay, independent enzyme-linked immunosorbent assay, and now the widespread application of nucleic acid test (NAT). Since 2010, the Chinese government has established NAT capacity in several blood centers; and in 2015, the government invested 900 million RMB on the nationwide expansion of NAT. Although the Chinese government has worked to enhance blood safety, many challenges remain. Concern exists for rising rates of HIV infection. The existence of occult HBV infection and the transmission of emerging blood-borne diseases continue to challenge the safety of the blood supply.

Myeloid-derived suppressor cells (MDSCs), one of the major orchestrators of the immunosuppressive network, are associated with immune suppression and considered a prime target for cancer immunotherapy. At present, various strategies have been explored to deplete and/or inactivate MDSCs in vivo. In this study, we investigated the effect of arsenic trioxide (ATO) on MDSCs derived from tumor-bearing mice. This study examined the in vitro and in vivo effects of ATO administration on MDSCs from C57/j mice bearing either the B16 or H22 tumor. The MDSCs were then characterized for phenotype, gene expression and function. Administration with ATO in vitro significantly induced MDSC differentiation, inhibited their proliferation and triggered apoptosis. Treatment with ATO in these murine tumor models significantly inhibited tumor growth and splenomegaly, decreased the percentages of MDSCs in the spleen, promoted their differentiation, reduced tumor necrosis factor-α and interleukin-10 levels and weakened the immune inhibition activity of MDSCs on T cells. In addition, we observed the underlying mechanism involved in the regulation of MDSCs by ATO, which included a panel of cytokines and signaling pathways. The findings showed the immunoregulatory effects of ATO by inducing apoptosis, promoting differentiation and inhibiting the function of MDSCs, suggesting that ATO has potential clinical benefit as it selectively attenuates MDSC-induced immunosuppression.

Maternal folate and vitamin B12 deficiency predict poor pregnancy outcome. To improve pregnancy outcomes in rural area of China, we investigate rural women's folic acid supplementation (FAS) status and the associations between maternal vitamin B status during the first trimester and subsequent adverse pregnancy outcomes. We collected the questionnaire information and drew 5 ml of blood from 309 early pregnant rural women. The birth outcomes were retrieved from medical records after delivery. Out of the total, 257 had taken FAS, including 50 before conception (group A) and 207 during the first trimester (group B). The concentration of plasma folate and the RBC folate supplementation groups were obviously higher than that of no-supplementation group (group N, p

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous myeloid cells that can suppress antitumor immunity. MDSCs are divided into granulocytic (G-MDSCs) and monocytic subsets. In the present study, the microRNA profiles of the G-MDSCs were determined and the differential expression of microRNAs between G-MDSCs from tumor-bearing mice and tumor-free mice was examined. The number of G-MDSCs in spleens of Lewis lung carcinoma (LLC)-bearing mice was ~6-fold higher than in spleens of normal mice (13.54±1.74% vs. 2.14±1.44%; P1.3-fold increased or decreased change were differentially expressed between the experimental and control group mice. The levels of nine of these differentially expressed miRNAs, miRNA-468 (miR-486), miR-192, miR-128, miR-125a, miR-149, miR-27a, miR-125b, miR-350 and miR-328, were also analyzed by RT-qPCR to validate the microarray data. The concordance rate between the results tested by the two methods was 88.9%. Bioinformatics analyses revealed that these miRNAs may act on various target genes, including Adar, Pik3r1, Rybp and Rabgap1, to regulate the survival, differentiation and the function of tumor-induced granulocytic MDSCs. The results revealed microRNAs and potential targets that may be vital for regulating survival, differentiation and function of G-MDSCs induced by LLC. Further investigation should be performed to clarify the roles of these microRNAs in regulating LLC-induced granulocytic MDSCs and the target genes that mediate their functions.

Background Hypertension is a leading cause of cardiovascular disease (CVD). The purpose of this study was to examine the effectiveness of community healthcare in controlling blood pressure (BP) and mitigating related risk factors after 5 y of follow-up. Methods Hierarchical clustering sampling was employed to choose a representative sample of 10 rural and 10 urban community populations (N=4235). The 5y prospective cohort study was completed by the medical group in the community clinical centre. Results The study included 4235 patients, median age 69 y (range 61–76), with hypertension in 2009; 2533 (59.81%) were female. The rate of BP control increased from 28.33% in 2009 to 64.05% in 2014. The BP control rate was higher in patients with CVD and kidney disease and lower in those with obesity than in those without. Comparing 2009 and 2014 values, the intervention resulted in median systolic BP and diastolic BP reductions of 7.0 mmHg and 6.5 mmHg, respectively. Age, medication treatment, antihypertensive agents, BP at baseline and follow-up, complications of diabetes, CVD, obesity and kidney disease, the aspartate aminotransferase:aminotransferase ratio and smoking were identified as risk factors for BP control. Conclusions Community management of hypertension by general practitioners achieved significant BP control over 5 y of intervention.

The presence of specific mutations in the EGFR gene informs the clinical pathway of therapy for patients with lung adenocarcinoma (LAC), including those with central nervous system (CNS) metastases. Plasma circulating cell-free DNA (cfDNA) has been demonstrated to carry the mutational information of LACs, which serves as a biomarker to guide treatment. However, whether the cerebrospinal fluid (CSF) enriches circulating tumor DNA (ctDNA) released from CNS metastatic lesions of LAC, and whether the CSF ctDNA can be used to characterize these lesions remains unknown. To explore the EGFR status in CNS metastases of LAC patients, and to guide the treatment of intra- and extracranial tumors in these patients. The EGFR mutational status in the cfDNA from paired CSF and plasma samples from LAC patients with CNS metastases, including 20 brain metastases (BM) and 15 leptomeningeal metastases (LM), was assessed by droplet digital polymerase chain reaction (ddPCR). The clinical outcomes of the EGFR status-based intervention were investigated. EGFR mutations were detected in 23/35 LAC patients (65.7%). EGFR mutations in the plasma or CSF were detected in 6/11 (54.5%) and 5/10 (50%) BM patients, and in 4/11 (36.4%) and 9/12(75%) LM patients, respectively. The prevalence of the T790M mutation was significantly higher in plasma (9/23) than in CSF (3/23) samples. The sensitivity and specificity of the ddPCR-based EGFR mutation test in CSF or plasma samples versus the primary tumor samples were 56% and 89% versus 46% and 100%, respectively. Twelve patients received a first-generation EGFR TKI (tyrosine kinase inhibitor) after the detection of sensitive EGFR mutations in their CSF or plasma, and five patients were switched from a first-generation EGFR TKI to osimertinib after the detection of the T790M mutation. The EGFR T790M mutation in plasma cfDNA is a sensitive marker for EGFR TKI resistance when CNS metastases progressed. CSF ctDNA increases the diagnostic validity for EGFR genotyping of lung cancer brain metastasis. ddPCR in CSF and plasma samples could provide less invasive and close monitoring of the EGFR status of LAC patients with CNS metastases.

Background The nucleic acid mutation status in intracranial metastasis is markedly significant clinically. The goal of the current study was to explore whether the tumor-associated mutations can be detected by different next-generation sequencing (NGS) pipelines in paired cerebrospinal fluid (CSF) and plasma samples from lung adenocarcinoma (LAC) patients with leptomeningeal metastases (LM). Methods Paired CSF cell free DNA (cfDNA), CSF cells, plasma and formalin-fixed and paraffin-embedded (FFPE) samples of primary tumors were collected from 29 LAC patients with LM to detect the mutations by different NGS pipelines. Results DNA libraries were generated successfully for 79 various samples in total for NGS sequencing, of which mutations were detected in 7 plasma samples (24.14%), 12 CSF cfDNA samples (66.67%), and 10 CSF cells (76.9%) samples. For the 26 patients with detected mutations, 8/26(30.77%) had mutations in plasma, which was significantly lower than that those from CSF cfDNA (12/15, 80.00%), CSF cells (10/11, 90.91%) and FFPE samples (13/17, 76.47%). When the input DNA of CSF cells was less than 20 ng, the cHOPE pipeline of NGS identified the most mutations for epidermal growth factor receptor (EGFR). Conclusions NGS-based detection of mutations in cfDNA or cells from CSF provided more information than from plasma samples from LAC patients with LM. In addition, the cHOPE pipeline performed better than the other three NGS pipelines when input DNA from CSF cells was low. Electronic supplementary material The online version of this article (10.1186/s12885-019-5348-3) contains supplementary material, which is available to authorized users.

Background Bronchopulmonary dysplasia (BPD) is a complex lung pathological lesion secondary to multiple factors and one of the most common chronic lung diseases. It has a poor prognosis, especially in preterm infants. However, effective therapies for this disease are lacking. Stem-cell therapy is a promising way to improve lung injury and abnormal alveolarization, and the human umbilical cord (hUC) is a good source of mesenchymal stem cells (MSCs), which have demonstrated efficacy in other diseases. We hypothesized that intravenously administered allogeneic hUC-MSCs are safe and effective for severe BPD. Methods The MSC-BPD trial is a randomized, single-center, open-label, dose-escalation, phase-II trial designed to investigate the safety and efficacy of hUC-MSCs in children with severe BPD. In this study, 72 patients will be enrolled and randomly divided into two intervention groups and one control group. Patients in the intervention groups will receive a low dose of hUC-MSCs (n = 24; 2.5 million cells/kg) or a high dose of hUC-MSCs (n = 24; 5 million cells/kg) in combination with traditional supportive treatments for BPD. The patients in the control group (n = 24) will be treated with traditional supportive treatments alone without hUC-MSCs. The primary outcome measures will be cumulative duration of oxygen therapy. Follow-up assessments will be performed at 1, 3, 6, 12, and 24 months post intervention, and the key outcome during follow-up will be changes on chest radiography. Statistical analyses will evaluate the efficacy of the hUC-MSC treatment. Discussion This will be the first randomized controlled trial to evaluate the safety and efficacy of intravenously administered hUC-MSCs in children with severe BPD. Its results should provide a new evidence-based therapy for severe BPD. Trial registration ClinicalTrials.gov, ID: NCT03601416. Registered on 26 July 2018.

The aim of this study is to determine whether lecithin retinol acyltransferase (LRAT) as well as biomarkers of vitamin A (VA) and vitamin D are related to indices of obesity in childhood. A total of 164 children (aged 6–12 years, female 49.39%), comprising 66 children in the overweight/obese group and 98 children in the lean group, were included. LRAT expression was remarkably lower in the overweight/obese group than in the lean group (P

Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) has been demonstrated to serve a vital role in tumor progression. However, the biological role and molecular mechanisms of TBL1XR1 in lung squamous cell carcinoma (SCC) remain largely unknown. The purpose of the present study was to investigate the biological role of TBL1XR1 and its mechanism in lung SCC. TBL1XR1 was expressed in a human bronchial epithelial cell line and in lung SCC cell lines. The present study analyzed TBL1XR1-induced proliferation, invasion and migration abilities in vitro using the cell counting kit-8 assay, cell invasion assay and wound healing assay, respectively. This study examined the effects of TBL1XR1 on epithelial-mesenchymal transition (EMT) in lung SCC cells and activation of the transforming growth factor (TGF)-β/mothers against decapentaplegic homolog (Smad) signaling pathway by western blotting. The results indicated that TBL1XR1 was upregulated in lung SCC cells. Overexpression of TBL1XR1 increased the rate of cell proliferation compared with the control group. In vitro, overexpression of TBL1XR1 promoted cell invasion and migration ability compared with the control group. In addition, overexpression of TBL1XR1 produced a mesenchymal phenotype, while cells with downregulated TBL1XR1 produced an epithelial phenotype. Overexpression of TBL1XR1 significantly increased E-cadherin protein expression whilst snail family transcriptional repressor 1 (SNAI1), zinc finger E-box binding homebox 1 (ZEB1), p-Smad2/3, Smad2 and Smad3 protein expression was significantly reduced, compared with the control group. Downregulation of TBL1XR1 produced the opposite results. The present study indicated that TBL1XR1 contributed to lung SCC development and progression, and therefore TBL1XR1 may be a potential therapeutic target. TBL1XR1 may induce EMT of lung SCC cells through activation of the TGF-β/Smad signaling pathway.

Background Host genetic polymorphisms influence the fibrosis progression of chronic hepatitis C (CHC) patients. Previous studies have shown the association of human platelet antigens (HPAs) polymorphisms with CHC. However, little is known regarding the association of HPAs polymorphisms with the fibrosis progression of CHC. The aim of this study was to determine the association of HPA -2, -3, -5 and -15 polymorphisms with the levels of serum fibrosis marks in CHC patients. Methods The HPA -2, -3, -5 and -15 were genotyped by 5ˊ-nuclease assay in 211 CHC patients, while the serum concentration of hyaluronic acid (HA), collagen IV (CIV), amino-terminal pro-peptide of type III procollagen (PIIINP), and laminin (LN) from the same samples were measured by time resolved fluorescence immunoassay. Results The level of serum LN was significantly lower in CHC patients with HPA-15aa genotype compared to those with HPA-15ab/bb (P = 0.032) but did not differ among HPA-2, -3 and -5 genotypes. There were no difference in HA, CIV and PIIINP levels among HPA-2, -3,-5 and -15 genotypes. Conclusions This study demonstrates that HPA-15 aa polymorphism is associated lower serum LN in CHC, which suggests that HPA -15 aa may be involved in the fibrosis progression of CHC.

Growing evidence indicates that phosphoserine phosphatase (PSPH) is up-regulated and correlates with prognosis in multiple types of cancer. However, little is known about the roles of PSPH in NSCLC. Thus, the aim of the present study was to demonstrate the expression of PSPH in human NSCLC and reveal its biological functions and the underlying mechanisms. qRT-PCR, western blot and immunohistochemistry were used to assess the expression of NSCLC patient specimens and NSCLC cell lines. The functions of PSPH in migration and invasion were determined using trans-well and wound-healing assays. Cell proliferation capacity was performed by cell counting kit-8 (CCK-8), colony formation assays and cell cycle analysis. We demonstrated that PSPH was overexpressed in NSCLC specimens compared with the adjacent non-tumorous specimens, and high expression of PSPH was associated with clinical stage, metastasis and gender in NSCLC. Decreased expression of PSPH inhibited NSCLC cells migration, invasion and proliferation. Most importantly, further experiments demonstrated that PSPH might regulate NSCLC progress through MAPK signaling pathways. Lastly, immunohistochemistry (IHC) revealed that the PSPH expression level was positively correlated with the clinical stage in NSCLC patients. These results suggest that PSPH may act as a putative oncogene and a potential therapeutic target in NSCLC.

Brain metastasis (BM) is the primary contributor to mortality in non-small cell lung cancer (NSCLC) patients. Although the findings of NSCLC genetic sequencing studies suggest the potential for personalizing therapeutic approaches, the genetic profiles and underlying mechanisms of BM progression remain poorly understood. Here, we investigated the genetic profiles of brain metastases from NSCLC in six patients with primary tumors and corresponding BM samples via whole exome sequencing and targeted panel sequencing. We have demonstrated considerable genetic heterogeneity between primary lung cancer and corresponding brain metastases specimens. High-frequency mutations were found in NOTCH2,NOTCH2NL,FANCD2,EGFR, and TP53. Additionally, EGFR and TP53 consistently exhibited high frequencies of mutation between primary tumors and corresponding brain metastases. The implication is that most of the genetic alterations may be acquired or lost during malignant progression, and the stable EGFR and TP53 mutational status between paired primary tumors and metastatic sites confirms that most mutations detected on analysis of the primary tumor or metastases are sufficient for clinical decision-making, and suggest there is no need to re-biopsy recurrent tumors or metastases for most NSCLC patients.

Although recent genome-wide association studies have identified a number of single nucleotide polymorphisms associated with platelet count and mean platelet volume (MPV), it is unclear whether polymorphisms in the human platelet antigens (HPA) genes are associated with platelet count and MPV. The aim of this study was to determine the association of the HPA-2, -3, -5 and -15 polymorphisms with platelet count and MPV.The HPA were genotyped by 5'-nuclease assay in 139 healthy Chinese Han individuals, while platelet count and MPV from the same samples were measured using an hematology cell analyzer.The platelet count was significantly lower in the individuals with the HPA-2aa genotype compared to those with HPA-2ab (P = 0.020), and significantly higher in individuals with HPA-5aa and HPA-15aa genotypes compared to those with HPA-5ab (P = 0.045) and HPA-15ab/bb (P = 0.032), respectively. On the other hand, platelet count of individuals with the HPA-3aa and HPA-3ab/bb genotypes did not differ significantly (P = 0.084). The MPV was significantly lower in individuals with HPA-5aa genotype compared to those with HPA-5ab (P = 0.001) but did not differ among the HPA-2, -3 and -15 genotypes. Furthermore, HPA-2, -5 and -15 polymorphisms were identified as independent factors for the platelet count and HPA-5 polymorphism was shown as an independent factor for MPV.This study demonstrates that HPA-2, -5 and -15 polymorphisms are associated with the platelet count while HPA-5 polymorphism is associated with MPV. This finding will further our understanding of the association of HPA polymorphisms with platelet-related diseases.

End-stage renal disease (ESRD), the last stage of chronic renal failure, is a global health problem. The number of ESRD patients worldwide is increasing faster than the number of kidneys available per year for renal transplantation. Most of the ESRD patients are awaiting renal transplantation. The immune response to the transplanted kidney is directed mainly against mismatched human leukocyte antigen (HLA) glycoproteins expressed on donor tissues. Thus, the analysis of HLA allele and haplotype polymorphisms is valuable not only for identifying ESRD susceptibility factors but also to improve graft survival.In this study, 163 Han ESRD patients were recruited to participate. The blood samples were genotyped by sequence-specific oligonucleotide method. A group of 14,529 healthy Chinese Han individuals registered at the Dalian Blood Center as bone marrow donors, living in the same region and of the same ethnicity, were used as controls.We found that only one allele, HLA-DRB1*12, showed a positive association with ESRD (p = 0.004, pThey were potentially valuable predictors for evaluating the risk of ESRD in the Dalian Han population.

The monocytic MDSC (M‐MDSC) is one of the major types of MDSCs, which play important roles in suppression of antitumor immunity. However, the mechanisms underlying how M‐MDSCs so heavily accumulate in patients with cancer are still poorly understood. The purpose of this study was to identify miRNAs that regulate the proliferation and differentiation of M‐MDSCs. Microarray analysis was performed to identify differentially expressed miRNAs between tumor‐induced M‐MDSCs (TM‐MDSCs) and their counterparts from tumor‐free mice. The miRNAs and their target genes that regulate the proliferation and differentiation of myeloid cells were predicted by bioinformatics analysis and validated by RT‐qPCR. Luciferase reporter assays were used to analyze the relationships between miRNAs and target genes. Overexpression of candidate miRNAs and target genes in myeloid cells was conducted to verify their functions in cell proliferation, differentiation, and apoptosis. Our data showed that miR‐486 was overexpressed in TM‐MDSCs. Cebpa was predicted to be one of the target genes of miR‐486 that regulates the proliferation of myeloid cells. Expression of Cebpa was inversely correlated with miR‐486 in TM‐MDSCs, and we found that overexpression of miR‐486 suppressed the expression of Cebpa in both 293T cells determined by luciferase reporter assays and in myeloid cells determined by RT‐qPCR. Overexpression of miR‐486 promoted proliferation and suppressed apoptosis in myeloid cells, as opposed to overexpression of Cebpa, which promoted the opposing phenotype. Overexpression of either miR‐486 or Cebpa inhibited differentiation of myeloid cells. This study indicates that miR‐486 promotes proliferation and suppresses apoptosis in myeloid cells by targeting Cebpa in vitro, suggesting that miR‐486 and Cebpa might be involved in the expansion of TM‐MDSCs in tumor‐bearing mice.

Lung cancer is the leading cause of cancer death in men and women worldwide. Brain metastasis (BMs) of non-small cell lung cancer (NSCLC) is the most important cause of death. This study aimed to explore the association of epidermal growth factor receptor (EGFR) mutations and BMs in NSCLC. We analyzed 50 NSCLC patients with BMs and 50 match-paired NSCLC patients with no brain metastases (NBMs). The EGFR mutation status of primary lesions was detected using the amplification refractory mutation system polymerase chain reaction. The BMs patients had a higher frequency of EGFR mutations than the NBMs patients (52.0 vs. 22.0% respectively, P

Background/Aims: MiR-19b has been reported to be involved in several malignancies, but its role in multiple myeloma (MM) is still unknown. The objective of this study was to explore the biological mechanism of miR-19b in the progression of MM. Methods: First, we performed real-time polymerase chain reaction (PCR) and Western blot to study the expression of miR-19b, tuberous sclerosis 1 (TSC1), and caspase-3 in different groups. MTT assay was performed to explore the effect of miR-19b on survival and apoptosis of cancer stem cells (CSCs). Computation analysis and luciferase assay were utilized to confirm the interaction between miR-19b and TSC1. Results: A total of 38 participants comprising 20 subjects with MM and 18 healthy subjects as normal controls were enrolled in our study. Real-time PCR showed dramatic upregulation of miR-19b, but TSC1 was evidently suppressed in the MM group. MiR-19b overexpression substantially promoted clonogenicity and cell viability, and further inhibited apoptosis of CSCs in vitro. Furthermore, miR-19b overexpression downregulated the expression of caspase-3, which induced apoptosis. Using in silico analysis, we identified that TSC1 might be a direct downstream target of miR-19b, and this was further confirmed by luciferase assay showing that miR-19b apparently reduced the luciferase activity of wild-type TSC1 3´-UTR, but not that of mutant TSC1 3´-UTR. There was also evident decrease in TSC1 mRNA and protein in CSCs following introduction of miR-19b. Interestingly, reintroduction of TSC1 abolished the miR-19b-induced proliferation promotion and apoptosis inhibition in CSCs. Conclusion: These findings collectively suggest that miR-19b promotes cell survival and suppresses apoptosis of MM CSCs via targeting TSC1 directly, indicating that miR-19b may serve as a potential and novel therapeutic target of MM based on miRNA expression.

Drought is one of the vitally critical environmental stresses affecting both growth and yield potential in rice. Drought resistance is a complicated quantitative trait that is regulated by numerous small effect loci and hundreds of genes controlling various morphological and physiological responses to drought. For this study, 270 rice landraces and cultivars were analyzed for their drought resistance. This was done via determination of changes in plant height and grain yield under contrasting water regimes, followed by detailed identification of the underlying genetic architecture via genome-wide association study (GWAS). We controlled population structure by setting top two eigenvectors and combining kinship matrix for GWAS in this study. Eighteen, five, and six associated loci were identified for plant height, grain yield per plant, and drought resistant coefficient, respectively. Nine known functional genes were identified, including five for plant height (OsGA2ox3, OsGH3-2, sd-1, OsGNA1, and OsSAP11/OsDOG), two for grain yield per plant (OsCYP51G3 and OsRRMh) and two for drought resistant coefficient (OsPYL2 and OsGA2ox9), implying very reliable results. A previous study reported OsGNA1 to regulate root development, but this study reports additional controlling of both plant height and root length. Moreover, OsRLK5 is a new drought resistant candidate gene discovered in this study. OsRLK5 mutants showed faster water loss rates in detached leaves. This gene plays an important role in the positive regulation of yield-related traits under drought conditions. We furthermore discovered several new loci contributing to the three investigated traits (plant height, grain yield, and drought resistance). These associated loci and candidate genes significantly improve our knowledge of the genetic control of these traits in rice. In addition, many drought resistant cultivars screened in this study can be used as parental genotypes to improve drought resistance of rice by molecular breeding.

The dynamic nature of the brain is critical for the success of treatments aimed at restoring vision at the retinal level. The success of these treatments relies highly on the functionality of the surviving neurons along the entire visual pathway. Electrophysiological properties at the retina level have been investigated during the progression of retinal degeneration; however, little is known about the changes in electrophysiological properties that occur in the primary visual cortex (V1) during the course of retinal degeneration. By conducting extracellular recording, we examined the electrophysiological properties of V1 in S334ter-line-3 rats (a transgenic model of retinal degeneration developed to express a rhodopsin mutation similar to that found in human retinitis pigmentosa patients). We measured the orientation tuning, spatial and temporal frequency tunings and the receptive field (RF) size for 127 V1 neurons from 11 S334ter-3 rats and 10 Long-Evans (LE) rats. V1 neurons in the S334ter-3 rats showed weaker orientation selectivity, lower optimal spatial and temporal frequency values and a smaller receptive field size compared to the LE rats. These results suggest that the visual cognitive ability significantly changes during retinal degeneration.

Purpose Chemotherapy-induced nausea and vomiting (CINV) in children remains to be a major side effect despite antiemetic treatment. Palonosetron is a new generation 5-HT3 receptor antagonists effective against acute and delayed nausea and vomiting. This study aimed to compare the therapeutic values of palonosetron and ondansetron in preventing pediatric CINV. Methods A prospective, randomized, double-blind, parallel controlled study was conducted in 0–18 years old cancer patients administered highly emetogenic chemotherapy, with different dosage of palonosetron or ondansetron, both followed by dexamethasone. The patients were observed for vomiting and nausea from 0 to 120 hr after chemotherapy initiation. All adverse events (AEs) during the study period were recorded. This study was registered with the Chinese Clinical Trial Registry, number ChiCTR-TRC-14004891. Results Between August 2014 and July 2016, 565 patients were randomly assigned to receive 5 μg/kg palonosetron (n = 185), 10 μg/kg palonosetron (n = 186), and 3 × 150 μg/kg ondansetron (n = 194), of whom 181, 185, and 189, respectively, were included in the efficacy analysis. Complete response (CR) rates during the acute phase were 69.1, 69.7, and 64.6%, respectively, in the 5 μg/kg palonosetron, 10 μg/kg palonosetron, and ondansetron groups. In the delayed phase, 10 μg/kg palonosetron (CR, 53.5%) showed superiority to 5 μg/kg palonosetron (CR, 39.8%) and ondansetron (CR, 32.8%) groups (P