Publications by authors named "Jianxin Hu"

94 Publications

Analysis of Clinical Trials on Therapies for Prostate Cancer in Mainland China and Globally from 2010 to 2020.

Front Oncol 2021 12;11:647110. Epub 2021 May 12.

Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China.

The overall aging of the world population has contributed to the continuous upward trend in the incidence of prostate cancer (PC). Trials on PC therapy have been extensively performed, but no study has analyzed the overall trends and characteristics of these trials, especially for those carried out in China. This study aimed to provide insights on the future direction of drug development in PC, thus supplying essential supportive data for stakeholders, including researchers, patients, investors, clinicians, and pharmaceutical industry. The details of the clinical trials of drug therapies for PC during January 1, 2010, to January 1, 2020, were collected from Pharmaprojects. A total of 463 clinical trials on different therapies with 132 different drugs were completed. The long-acting endocrine therapy with few side effects, radiotherapy combined with immune checkpoint inhibitors, gene-targeted chemotherapeutics, and novel immunotherapeutic products changed the concept of PC treatment. In mainland China, 31 trials with 19 drugs have been completed in the 10 assessment years. China has initiated a few trials investigating a limited number of drug targets, centered in a markedly uneven geographical distribution of leading clinical trial units; hence, the development of PC drugs has a long way to go. Given the large patient pool, China deserves widespread attention for PC drug research and development. These findings might have a significant impact on scientific research and industrial investment.
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http://dx.doi.org/10.3389/fonc.2021.647110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167212PMC
May 2021

The atmospheric concentrations and emissions of major halocarbons in China during 2009-2019.

Environ Pollut 2021 May 14;284:117190. Epub 2021 May 14.

State Key Joint Laboratory for Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, China. Electronic address:

Due to the characteristics of ozone-depleting and high global warming potential, chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs) and hydrofluorocarbons (HFCs) have been restricted by the Montreal Protocol and its amendments over the world. Considering that China is one of the main contributors to the emission of halocarbons, a long-term atmospheric observation on major substances including CFC-11 (CClF), CFC-12 (CClF), HCFC-22 (CHClF), HCFC-141b (CHCClF), HCFC-142b (CHCClF) and HFC-134a (CHFCF) was conducted in five cities (Beijing, Hangzhou, Guangzhou, Lanzhou and Chengdu) of China during 2009-2019. The atmospheric concentrations of CFC-11, CFC-12, HCFC-141b and HCFC-142b all showed declining trends on the whole while those of HCFC-22 and HFC-134a were opposite. A paired sample t-test showed that the ambient mixing ratios of HCFC-22 and HFC-134a in cities were 41.9% and 25.7% higher on average than those in suburban areas, respectively, while the other substances did not show significant regional differences. The annual emissions of halocarbons were calculated using an interspecies correlation method and the results were generally consistent with the published estimates. Discrepancies between bottom-up inventories and the estimates in this study for CFCs emissions were found. Among the most consumed ozone depleting substances (ODSs) in China, CFCs accounted for 75.1% of the ozone depletion potential (ODP)-weighted emissions while HCFCs contributed a larger proportion (58.6%) of CO-equivalent emissions in 2019. China's emissions of HCFC-141b and HCFC-142b contributed the most to the global emission (17.8%-48.0%). The elimination of HCFCs in China will have a crucial impact on the HCFCs phase-out in the world.
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http://dx.doi.org/10.1016/j.envpol.2021.117190DOI Listing
May 2021

Automated detection of hippocampal sclerosis: Comparison of a composite MRI-based index with conventional MRI measures.

Epilepsy Res 2021 Aug 9;174:106638. Epub 2021 Apr 9.

Department of Radiology, Sanbo Brain Hospital, Capital Medical University, China. Electronic address:

Purpose: This study aims to compare the performance of an MRI-based composite index (HSI) with conventional MRI-based measures in hippocampal sclerosis (HS) detection and postoperative outcome estimation.

Methods: Seventy-two temporal lobe epilepsy (TLE) patients with pathologically confirmed HS and fifteen TLE patients without HS were included retrospectively. The T1-weighted and FLAIR images of these patients were processed with AccuBrain to quantify the hippocampal volume (HV) and the hippocampal FLAIR signal. The HSI index that considered both HV and hippocampal FLAIR signal was also calculated. Two experienced neuropathologists rated the HS severity with the resected tissue and reached an agreement for all cases. The asymmetry indices of the MRI measures were used to lateralize the sclerotic side, and the original MRI measures were applied to detect HS vs. normal hippocampi. Operating characteristic curve (ROC) analyses were performed for these predictions. We also investigated the sensitivity of the ipsilateral MRI measures in characterizing the pathological severity of HS and the associations of the MRI measures with postoperative outcomes (Engel class categories).

Results: With the optimal cutoffs, the asymmetry indices of HSI and HV both achieved excellent performance in differentiating left vs. right HS (accuracy = 100 %), and the absolute value of the asymmetry index of HSI performed best in differentiating unilateral vs. bilateral HS (accuracy = 91.7 %). Regarding the detection of HS, HSI performed better in sensitivity (94.4 % vs. 87.5 %) while HV performed better in specificity (93.6 % vs. 89.4 %) when the contralateral site of unilateral HS and both sides of non-HS patients were considered as the normal reference, and HSI performed even better than HV when only both sides of non-HS patients were considered as the normal reference (AUC: 0.956 vs. 0.934, p = 0.038). The ipsilateral HSI presented the strongest association with the pathological rating of HS severity (r = 0.405, p < 0.001). None of the ipsilateral or contralateral MRI measures was associated with the postoperative outcomes. Among the asymmetry indices, only the absolute value of the asymmetry index of HV presented a significant association with the Engel classifications for the Year 2∼3 visit (r = -0.466, p = 0.004) or the latest visit with >1 year follow-up (r = -0.374, p = 0.003) while controlling for disease duration and follow-up duration.

Conclusion: The HSI index and HV presented comparable good performance in HS detection, and HSI may have better sensitivity than HV in differentiating pathological HS severity. Higher magnitude of HV dissymmetry may indicate better post-surgical outcomes for HS patients.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106638DOI Listing
August 2021

Comparison of the efficacy and safety of different doses of nifekalant in the instant cardioversion of persistent atrial fibrillation during radiofrequency ablation.

Basic Clin Pharmacol Toxicol 2021 Mar 21;128(3):430-439. Epub 2020 Oct 21.

Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Nifekalant has been used in the treatment of atrial arrhythmia recently. However, there is no consensus on the preferable nifekalant dose to treat atrial fibrillation (AF). The purpose of this study was to explore efficacy and safety of different doses of nifekalant in the cardioversion of persistent AF. The study was a single-centre, randomized controlled trial. All subjects received nifekalant or placebo intravenously, and the nifekalant was given at the dosage of 0.3, 0.4 or 0.5 mg/kg. Primary efficacy end-point: compared with 0.3 mg group, the rate of cardioversion to sinus rhythm from AF in 0.4 and 0.5 mg group was higher. The 0.4 and 0.5 mg/kg doses were associated with a similar magnitude of efficacy (P > .05). Secondary efficacy end-point: termination rates of AF in the group of 0.4 mg and 0.5 mg were higher than 0.3 mg. Primary safety end-point: the rate of Torsades de Pointes or ventricular fibrillation was numerically lower in the 0.4 mg group than 0.5 mg group (P = .02). Secondary safety end-point: The rates of the majority of other common drug-related adverse events in the group of 0.5 and 0.4 mg were higher than the 0.3 mg group. A 0.4 mg/kg dose of intravenous nifekalant may be recommended during the radiofrequency ablation for persistent AF considering the benefit-risk profile.
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http://dx.doi.org/10.1111/bcpt.13513DOI Listing
March 2021

Chronic exposure to di-n-butyl phthalate causes reproductive toxicity in zebrafish.

J Appl Toxicol 2020 12 5;40(12):1694-1703. Epub 2020 Jul 5.

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.

Di-n-butyl phthalate (DBP) is known to have adverse effects on reproduction in mammals and is pervasive in the aquatic environment. The objective of the present study was to investigate whether long-term exposure to low concentrations of DBP can affect fish reproduction. In this study, zebrafish (Danio rerio) embryos (F ) were exposed to low concentrations (4.9, 13.6 and 43.8 μg/L) of DBP from 2 hours post-fertilization until sexual maturation. The results demonstrate that chronic exposure to DBP (43.8 μg/L) impaired the reproductive function of zebrafish, as verified by reduced egg production and modifications to gonadal histology of the treated fish. Plasma 17β-estradiol levels in female zebrafish decreased significantly in a concentration-dependent manner, while testosterone levels in males increased significantly when fish were exposed to 43.8 μg/L DBP. Real-time polymerase chain reaction was performed to examine selected genes in the hypothalamic-pituitary-gonadal (HPG) axis and liver. Hepatic vitellogenin gene transcription was downregulated in both males and females, suggesting that DBP possesses anti-estrogenic activity. The disturbed steroid hormones were accompanied by the significant alterations in gene expression along the HPG axis. Additionally, parental exposure to DBP caused reduced hatching and survival rate as well as decreased growth in the F generation. Taken together, these results demonstrate that long-term exposure to low concentrations of DBP in zebrafish could cause reproductive toxicity, implying that DBP could have significant adverse effects on fish populations, particularly in a highly DBP-contaminated aquatic environment.
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http://dx.doi.org/10.1002/jat.4030DOI Listing
December 2020

The N-Terminal Acetyltransferase Naa50 Regulates Arabidopsis Growth and Osmotic Stress Response.

Plant Cell Physiol 2020 Sep;61(9):1565-1575

College of Life Sciences, Capital Normal University, Beijing 100048, China.

N-terminal acetylation (Nt-acetylation) is one of the most common protein modifications in eukaryotes. The function of Naa50, the catalytic subunit of the evolutionarily conserved N-terminal acetyltransferase (Nat) E complex, has not been reported in Arabidopsis. In this study, we found that a loss of Naa50 resulted in a pleiotropic phenotype that included dwarfism and sterility, premature leaf senescence and a shortened primary root. Further analysis revealed that root cell patterning and various root cell properties were severely impaired in naa50 mutant plants. Moreover, defects in auxin distribution were observed due to the mislocalization of PIN auxin transporters. In contrast to its homologs in yeast and animals, Naa50 showed no co-immunoprecipitation with any subunit of the Nat A complex. Moreover, plants lacking Naa50 displayed hypersensitivity to abscisic acid and osmotic stress. Therefore, our results suggest that protein N-terminal acetylation catalyzed by Naa50 plays an essential role in Arabidopsis growth and osmotic stress responses.
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http://dx.doi.org/10.1093/pcp/pcaa081DOI Listing
September 2020

miR-155-5p Promotes Oxalate- and Calcium-Induced Kidney Oxidative Stress Injury by Suppressing MGP Expression.

Oxid Med Cell Longev 2020 4;2020:5863617. Epub 2020 Mar 4.

Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China.

Oxalate and calcium are the major risk factors for calcium oxalate (CaOx) stone formation. However, the exact mechanism remains unclear. This study was designed to confirm the potential function of miR-155-5p in the formation of CaOx induced by oxalate and calcium oxalate monohydrate (COM). The HK-2 cells were treated by the different concentrations of oxalate and COM for 48 h. We found that oxalate and COM treatment significantly increased ROS generation, LDH release, cellular MDA levels, and HO concentration in HK-2 cells. The results of qRT-PCR and western blot showed that expression of NOX2 was upregulated, while that of SOD-2 was downregulated following the treatment with oxalate and COM in HK-2 cells. Moreover, the results of miRNA microarray analysis showed that miR-155-5p was significantly upregulated after oxalate and COM treated in HK-2 cells, but miR-155-5p inhibitor treatment significantly decreased ROS generation, LDH release, cellular MDA levels, and HO concentration in HK-2 cells incubated with oxalate and COM. miR-155-5p negatively regulated the expression level of MGP via directly targeting its 3'-UTR, verified by the Dual-Luciferase Reporter System. In vivo, polarized light optical microphotography showed that CaOx crystal significantly increased in the high-dose oxalate and Ca groups compared to the control group. Furthermore, IHC analyses showed strong positive staining intensity for the NOX-2 protein in the high-dose oxalate and Ca-treated mouse kidneys, and miR-155-5p overexpression can further enhance its expression. However, the expression of SOD-2 protein was weakly stained. In conclusion, our study indicates that miR-155-5p promotes oxalate- and COM-induced kidney oxidative stress injury by suppressing MGP expression.
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http://dx.doi.org/10.1155/2020/5863617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081043PMC
October 2020

Atmospheric perfluoroalkyl acid occurrence and isomer profiles in Beijing, China.

Environ Pollut 2019 Dec 31;255(Pt 1):113129. Epub 2019 Aug 31.

State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, 999007, PR China.

The airborne occurrence, isomer profiles, and phase distribution of perfluoroalkyl acids (PFAAs), including perfluoroalkyl carboxylates (PFCAs) and sulfonates (PFSAs), have received little scientific attention to date. Here we collected gaseous and particulate phase (PM) samples in China, between June and November 2013, using alkalized annular denuders and downstream filters toavoid sampling artefacts associated with traditional air sampling. We analysed the concentrations of 18 linear PFAAs and the branched isomers of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS). Concentrations of total PFAAs were dominated by PFCAs, with a range of 6.6-610 pg/m in the gaseous phase and 2.3-290 pg/m in the particulate phase. Concentrations of total PFCAs were higher in summer than winter in both phases. Branched PFOA isomers accounted for 10-22% of total PFOA in the gaseous phase and 13-24% in the particulate phase, which is close to, but slightly lower than, their abundance in the commercial PFOA mixtures manufactured using the electrochemical fluorination (ECF) process. In contract, branched PFOS isomers accounted for 26-63% of total PFOS in the gaseous phase and 39-77% in the particulate phase, which is much higher than their abundance in commercial PFOS mixtures manufactured by ECF. Most PFCAs had mean particle-associated fractions (Φ) higher than 0.5. PFHxS had a much higher mean Φ (0.65) than linear PFOS (0.31). We hypothesise that PFAAs observed in Beijing air may originate from the local water bodies through processes such as aerosol generation, although transformation of precursors also contribute.
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http://dx.doi.org/10.1016/j.envpol.2019.113129DOI Listing
December 2019

The efficacy of remote ischemic conditioning in preventing contrast-induced nephropathy among patients undergoing coronary angiography or intervention: An updated systematic review and meta-analysis.

Ann Noninvasive Electrocardiol 2020 03 11;25(2):e12706. Epub 2019 Oct 11.

Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Background: Numerous trials have investigated the effect of remote ischemic conditioning (RIC) in preventing contrast-induced nephropathy (CIN) in patients receiving contrast medium (CM). This meta analysis aims to validate the role of RIC in preventing CIN.

Methods: We searched the PubMed, EMBASE, and Web of Science databases for eligible randomized controlled trials (RCTs) published before April 27, 2019. Two investigators independently extracted basic characteristics from each study. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to examine the treatment effect.

Results: A total of 18 studies comprising 2,503 patients were included in our meta-analysis. Compared with conventional therapy, RIC significantly reduced the risk of CIN (OR = 0.43, 95% CI: 0.33, 0.56, p < .05). Subgroup analyses showed that the protective effect of RIC was stronger in the low-osmolar contrast media group (OR = 0.32; 95% CI: 0.23, 0.45, p < .05) and the nondiabetic group (OR = 0.39; 95% CI: 0.29, 0.53 p < .05). RIC also significantly reduced major adverse cardiovascular events within the first 6 months (OR = 0.39; p < .05), but the influence was not present after long-term follow-up.

Conclusions: Our meta-analysis showed that RIC could effectively reduce CIN risk and decrease the short-term incidence of relevant adverse events. Furthermore, the effects of CIN are more pronounced in nondiabetic patients and with the use of low-osmolar contrast medium. This meta-analysis of small trials suggests a possible protective effect of RIC on contrast-induced nephropathy and favors the performance of a large randomized trial to further investigate this strategy.
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http://dx.doi.org/10.1111/anec.12706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358796PMC
March 2020

Decreased eGFR Is Associated With Ischemic Stroke in Patients With Dilated Cardiomyopathy.

Clin Appl Thromb Hemost 2019 Jan-Dec;25:1076029619866909

1 Department of Cardiovascular Medicine, the second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China.

Dilated cardiomyopathy (DCM) is increasingly indicated as a cause of cardioembolic syndrome, in particular, cardioembolic ischemia stroke. However, the potential risk factors for stroke among DCM patients remain under investigated. DCM patients hospitalized from June 2011 to June 2016 were included. The cases were defined as the group of DCM patients with stroke compared with those without stroke. Clinical characteristic data were collected and compared between the two groups including demographic data, complicated diseases, echocardiography index, and laboratory parameters and estimated glomerular filtration rate (eGFR). A multivariate logistic regression analysis model adjusted by sex and age was used to explore the related risk factors for stroke in DCM patients. A total of 779 hospitalized patients with DCM were included. Of these, 55 (7.1%) had experienced a stroke. Significantly lower eGFR levels (68.03 ± 26.22 vs 79.88 ± 24.25 mL/min/1.73 m, = .001) and larger left atrial diameters (45.32 ± 7.79 vs 43.25 ± 7.11 mm, = .04) were found in the group of patients having DCM with stroke compared to those without stroke. When the eGFR was categorized as eGFR >60, 30
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http://dx.doi.org/10.1177/1076029619866909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829634PMC
January 2020

Efficacy of Nifekalant in Patients With Wolff-Parkinson-White Syndrome and Atrial Fibrillation: Electrophysiological and Clinical Findings.

J Am Heart Assoc 2019 07 25;8(13):e012511. Epub 2019 Jun 25.

1 Department of Cardiovascular Medicine The Second Affiliated Hospital of Nanchang University Nanchang of Jiangxi China.

Background The efficacy of nifekalant in preexcited atrial fibrillation ( AF ) has not been assessed. Methods and Results The study populations consisted of patients with sustained preexcited AF (n=51), paroxysmal supraventricular tachycardia (n=201), and persistent AF (n=87). Effects of intravenous infusion of nifekalant were assessed on electrophysiological and clinical parameters. Nifekalant prolonged the shortest preexcited R-R, the average preexcited R-R, and the average R-R intervals from 290±35 to 333±44 ms, 353±49 to 443±64 ms, and 356±53 to 467±75 ms, respectively, in patients with preexcited AF (all P<0.001). Nifekalant also decreased the percentage of preexcited QRS complexes, heart rate, and increased systolic pressure (all P<0.001). Nifekalant terminated AF in 33 of 51 patients (65%). Similar effects were also observed in a subgroup of 12 patients with preexcited AF and impaired left ventricular function. In patients with paroxysmal supraventricular tachycardia, nifekalant significantly prolonged the effective refractory period, the block cycle length of the antegrade accessory pathway, and the atrial effective refractory period (all P<0.001). Nifekalant had no effect on the effective refractory period of the antegrade atrioventricular node. Finally, in patients with persistent AF without an accessory pathway, nifekalant did not significantly decrease the ventricular rate of AF . One patient developed Torsades de Pointes. No other adverse effects were observed. Conclusions Nifekalant prolongs the effective refractory period of the antegrade accessory pathway and atrium without blocking antegrade conduction through the atrioventricular node, leading to slowing and/or to termination of preexcited AF . Thus, nifekalant might be an effective and a relatively safe drug in patients with preexcited AF .
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http://dx.doi.org/10.1161/JAHA.119.012511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662361PMC
July 2019

The Prognostic Significance of Gene during the Tumorigenesis of Prostate Cancer.

Cancer Invest 2019 11;37(4-5):199-208. Epub 2019 Jun 11.

c Department of Urology , The First Affiliated Hospital of Chongqing Medical University , Chongqing , PR China.

Prostate cancer (PCa) is the most common malignant tumor for men. But the mechanism is unclear. was shown to be overexpressed in PCa tissues and cell lines. overexpression was correlated to age and tumor stage in PCa patients and indicated poor survival. The proliferation, migration, and invasiveness of PC3 cells were all inhibited after knockdown. Additionally, the phosphorylation level of PI3K and Akt was downregulated while total NF-κB and Myc decreased after knockdown. But the expression of IκB increased reversely. Therefore, at least partially regulates the activity of PI3K/Akt/NF-κB signaling pathway in PC3 cells.
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http://dx.doi.org/10.1080/07357907.2019.1618322DOI Listing
July 2019

Venous endothelin modulates responsiveness of cardiac sympathetic axons to arterial semaphorin.

Elife 2019 02 8;8. Epub 2019 Feb 8.

The Saban Research Institute, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, United States.

Developing neurons of the peripheral nervous system reach their targets via cues that support directional growth, a process known as axon guidance. In investigating how sympathetic axons reach the heart in mice, we discovered that a combination of guidance cues are employed in sequence to refine axon outgrowth, a process we term second-order guidance. Specifically, endothelin-1 induces sympathetic neurons expressing the receptor Ednra to project to the vena cavae leading to the heart. Endothelin signaling in turn induces expression of the repulsive receptor Plexin-A4, via induction of the transcription factor MEF2C. In the absence of endothelin or plexin signaling, sympathetic neurons misproject to incorrect competing vascular trajectories (the dorsal aorta and intercostal arteries). The same anatomical and physiological consequences occur in ; double heterozygotes, genetically confirming functional interaction. Second-order axon guidance therefore multiplexes a smaller number of guidance cues in sequential fashion, allowing precise refinement of axon trajectories.
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http://dx.doi.org/10.7554/eLife.42528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389285PMC
February 2019

Correlation of SOX9 and NM23 genes with the incidence and prognosis of prostate cancer.

Oncol Lett 2019 Feb 12;17(2):2296-2302. Epub 2018 Dec 12.

Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. China.

Correlation of sex determining region Y-box (SOX)9 and NM23 genes with the incidence and prognosis of prostate cancer (PC) was investigated. SOX9-small interfering ribonucleic acid (siRNA) and NM23-siRNA were constructed and transfected into PC-3 cells. The expression levels of SOX9 and NM23 messenger RNAs (mRNAs) and proteins in PC-3 cells were detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. MTT assay was adopted to examine the proliferation ability of the transfected cells, and Transwell assay was applied to detect the migration ability of the transfected cells. Sixty-three patients with PC and 56 patients with benign prostatic hyperplasia who were treated in Huadu District People's Hospital were enrolled. Correlation analyses were conducted for the relative expression levels of SOX9 and NM23 and the Gleason grade; and the survival curves of the patient SOX9/NM23 (S/N) Cq values were plotted. The proliferation and migration abilities of PC-3 cells were remarkably reduced after low expression of SOX9 (P<0.01), while those of PC-3 cells were significantly improved after low expression of NM23 (P<0.01). Compared with that in tissues of PC patients, the relative expression of SOX9 mRNA in patients with benign prostatic hyperplasia was obviously decreased (P<0.01), while that of NM23 mRNA was significantly elevated (P<0.01). The larger the S/N was, the shorter the patient's survival time would be (P<0.05). The low expression of SOX9 gene can significantly reduce the proliferation and migration abilities of PC cells, which is negatively associated with the incidence and prognosis of patients. The low expression of NM23 gene can markedly enhance the proliferation and migration abilities of PC cells, and it is positively related to the incidence and prognosis of patients.
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http://dx.doi.org/10.3892/ol.2018.9828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341668PMC
February 2019

Comparative study of the binding mode between cytochrome P450 17A1 and prostate cancer drugs in the absence of haem iron.

J Biomol Struct Dyn 2019 10 11;37(16):4161-4170. Epub 2019 Jan 11.

Department of Urology, Guizhou Provincial People's Hospital , Guiyang , Guizhou Province , PR China.

According to the X-ray crystal structures of CYP17A1 (including its complexes with inhibitors), it is shown that a hydrogen bond exists between CYP17A1 and its inhibitors (such as abiraterone and TOK-001). Previous short MD simulations (50 ns) suggested that the binding of abiraterone to CYP17A1 is stronger than that of TOK-001. In this work, by carrying out long atomistic MD simulations (200 ns) of CYP17A1 and its complexes with abiraterone and TOK-001, we observed a binding mode between CYP17A1 and abiraterone, which is different from the binding mode between CYP17A1 and TOK-001. In the case of abiraterone binding, the unfilled volume in the active site cavity increases the freedom of movement of abiraterone within CYP17A1, leading to the collective motions of the helices G and B' as well as the breaking of hydrogen bond existing between the 3β-OH group of abiraterone and N202 of CYP17A1. However, the unfilled volume in the active site cavity can be occupied by the benzimidazole ring of TOK-001, restraining the motion of TOK-001. By pulling the two inhibitors (abiraterone and TOK-001) out of the binding pocket in CYP17A1, we discovered that abiraterone and TOK-001 were moved from their binding sites to the surface of protein similarly through the channels formed by the helices G and B'. In addition, based on the free energy calculations, one can see that it is energetically favorable for the two inhibitors (abiraterone and TOK-001) to enter into the binding pocket in CYP17A1.
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http://dx.doi.org/10.1080/07391102.2018.1540360DOI Listing
October 2019

Genomic analysis of transcriptional networks directing progression of cell states during MGE development.

Neural Dev 2018 09 14;13(1):21. Epub 2018 Sep 14.

Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, 94143, USA.

Background: Homeodomain (HD) transcription factor (TF) NKX2-1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. NKX2-1 defines MGE regional identity in large part through transcriptional repression, while specification and maturation of GABAergic and cholinergic fates is mediated in part by transcriptional activation via TFs such as LHX6 and LHX8. Here we analyze the signaling and TF pathways, downstream of NKX2-1, required for GABAergic and cholinergic neuron fate maturation.

Methods: Differential ChIP-seq analysis was used to identify regulatory elements (REs) where chromatin state was sensitive to change in the Nkx2-1cKO MGE at embryonic day (E) 13.5. TF motifs in the REs were identified using RSAT. CRISPR-mediated genome editing was used to generate enhancer knockouts. Differential gene expression in these knockouts was analyzed through RT-qPCR and in situ hybridization. Functional analysis of motifs within hs623 was analyzed via site directed mutagenesis and reporter assays in primary MGE cultures.

Results: We identified 4782 activating REs (aREs) and 6391 repressing REs (rREs) in the Nkx2-1 conditional knockout (Nkx2-1cKO) MGE. aREs are associated with basic-Helix-Loop-Helix (bHLH) TFs. Deletion of hs623, an intragenic Tcf12 aRE, caused a reduction of Tcf12 expression in the sub-ventricular zone (SVZ) and mantle zone (MZ) of the MGE. Mutation of LHX, SOX and octamers, within hs623, caused a reduction of hs623 activity in MGE primary cultures.

Conclusions: Tcf12 expression in the SVZ of the MGE is mediated through aRE hs623. The activity of hs623 is dependent on LHX6, SOX and octamers. Thus, maintaining the expression of Tcf12 in the SVZ involves on TF pathways parallel and genetically downstream of NKX2-1.
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http://dx.doi.org/10.1186/s13064-018-0119-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138899PMC
September 2018

Changes in Emissions of Ozone-Depleting Substances from China Due to Implementation of the Montreal Protocol.

Environ Sci Technol 2018 10 11;52(19):11359-11366. Epub 2018 Sep 11.

Center for Global Change Science , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.

The ozone layer depletion and its recovery, as well as the climate influence of ozone-depleting substances (ODSs) and their substitutes that influence climate, are of interest to both the scientific community and the public. Here we report on the emissions of ODSs and their substitute from China, which is currently the largest consumer (and emitter) of these substances. We provide, for the first time, comprehensive information on ODSs and replacement hydrofluorocarbon (HFC) emissions in China starting from 1980 based on reported production and usage. We also assess the impacts (and costs) of controls on ODS consumption and emissions on the ozone layer (in terms of CFC-11-equivalent) and climate (in CO-equivalent). In addition, we show that while China's future ODS emissions are likely to be defined as long as there is full compliance with the Montreal Protocol; its HFC emissions through 2050 are very uncertain. Our findings imply that HFC controls over the next decades that are more stringent than those under the Kigali Amendment to the Montreal Protocol would be beneficial in mitigating global climate change.
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http://dx.doi.org/10.1021/acs.est.8b01280DOI Listing
October 2018

Chemotherapy with or without pemetrexed as second-line regimens for advanced non-small-cell lung cancer patients who have progressed after first-line EGFR TKIs: a systematic review and meta-analysis.

Onco Targets Ther 2018 27;11:3697-3703. Epub 2018 Jun 27.

Department of Oncology, The People's Hospital of Nanhai Foshan, Foshan, China,

Purpose: The development of acquired resistance to the first-line epidermal growth factor-tyrosine kinase inhibitor (EGFR-TKI) treatment in non-small-cell lung cancer (NSCLC) is inevitable, and most of these patients needed second-line chemotherapy. Furthermore, the optimum chemotherapeutic regimen is unclear. The aim of this meta-analysis was to evaluate the chemotherapeutic regimens "with-pemetrexed" versus "non-pemetrexed" in advanced NSCLC patients who had progressed after first-line EGFR-TKIs.

Materials And Methods: We searched PubMed, Embase, Cochrane Library, and the Web of science for relevant clinical trials. Outcomes analyzed were response rate (RR), disease control rate (DCR), 1-year survival rate (1-year SR), progression-free survival (PFS), and overall survival (OS).

Results: One randomized controlled trial (RCT) and three retrospective studies were included in this meta-analysis, covering a total of 354 patients. The results showed that there was no significant difference between with-pemetrexed arm and non-pemetrexed arm in RR (OR 1.43, 95% CI 0.85-2.41, =0.18), DCR (OR 1.5, 95% CI 0.94-2.39, =0.09), and 1-year SR (OR 1.47, 95% CI 0.79-2.74, =0.22). But the with-pemetrexed chemotherapeutic regimens significantly improved the PFS (HR 0.61, 95% CI 0.46-0.81, =0.0005) and OS (HR 0.62, 95% CI 0.42-0.90, =0.01).

Conclusion: The second-line with-pemetrexed chemotherapeutic regimens provided significantly longer PFS and OS than non-pemetrexed chemotherapeutic regimens. These findings indicate that the with-pemetrexed chemotherapeutic regimen may be an optimal second-line chemotherapeutic regimen for patients with advanced NSCLC following EGFR-TKI failure.
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http://dx.doi.org/10.2147/OTT.S160147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027845PMC
June 2018

A multi-body dynamics based numerical modelling tool for solving aquatic biomimetic problems.

Bioinspir Biomim 2018 07 3;13(5):056001. Epub 2018 Jul 3.

Department of Naval Architecture, Ocean and Marine Engineering, University of Strathclyde, Glasgow, United Kingdom.

In this paper, a versatile multi-body dynamic algorithm is developed to integrate an incompressible fluid flow with a bio-inspired multibody dynamic system. Of particular interest to the biomimetic application, the algorithm is developed via four properly selected benchmark verifications. The present tool has shown its powerful capability for solving a variety of biomechanics fish swimming problems, including self-propelled multiple degrees of freedom with a rigid undulatory body, multiple deformable fins and an integrated system with both undulatory fish body and flexible fins. The established tool has paved the way for future investigation on more complex bio-inspired robots and live fish, for either propulsion or manoeuvring purposes.
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http://dx.doi.org/10.1088/1748-3190/aacd60DOI Listing
July 2018

O-GlcNAcylation of cardiac Nav1.5 contributes to the development of arrhythmias in diabetic hearts.

Int J Cardiol 2018 06 27;260:74-81. Epub 2018 Feb 27.

Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China; Jiangxi Key Laboratory of Molecular Medicine, Nanchang, Jiangxi 330006, China. Electronic address:

Background: Cardiovascular complications are major causes of mortality and morbidity in diabetic patients. The mechanisms underlying the progression of diabetic heart (DH) to ventricular arrhythmias are unclear. O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes. The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias.

Methods And Results: In this study, Sprague-Dawley rats (male, 200-230 g) were treated with a single high-dose of streptozotocin (STZ, 80 mg/kg) to generate a rat model of diabetes. STZ-induced 3-month diabetic rats displayed increased susceptibility to ventricular arrhythmias. The elevated O-GlcNAc modification was correlated with decreases in both total and cytoplasmic Nav1.5 expression in vivo and in vitro. In addition, both co-immunoprecipitation and immunostaining assays demonstrated that hyperglycemia could increase the O-GlcNAc-modified Nav1.5 levels and decrease the interaction between Nav1.5 and Nav1.5-binding proteins Nedd4-2/SAP-97. Furthermore, patch-clamp measurements in HEK-293 T cells showed that Nav1.5 current densities decreased by 30% after high-glucose treatment, and the sodium currents increased via O-GlcNAc inhibition.

Conclusion: Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval. Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
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http://dx.doi.org/10.1016/j.ijcard.2018.02.099DOI Listing
June 2018

Impacts of the Degradation of 2,3,3,3-Tetrafluoropropene into Trifluoroacetic Acid from Its Application in Automobile Air Conditioners in China, the United States, and Europe.

Environ Sci Technol 2018 03 14;52(5):2819-2826. Epub 2018 Feb 14.

State Key Joint Laboratory for Environmental Simulation and Pollution Control , College of Environmental Sciences and Engineering, Peking University , Beijing 100871 , China.

HFO-1234yf (2,3,3,3-tetrafluoropropene) was proposed as an automobile air conditioner (MAC) refrigerant worldwide. However, its atmospheric degradation product is the highly soluble and phytotoxic trifluoroacetic acid (TFA), which persists in aquatic environments. We used a global three-dimensional chemical transport model to assess the potential environmental effects resulting from complete future conversion of the refrigerant in all MAC to HFO-1234yf in China, the United States, and Europe. The annual mean atmospheric concentrations of HFO-1234yf were 2.62, 2.20, and 2.73 pptv, and the mean deposition rates of TFA were 0.96, 0.45, and 0.52 kg km yr, in three regions. The regional TFA deposition sources mainly came from emissions within the same region. The annual TFA deposition in the North Pole region was lower than the global average and mainly originated from European emissions. A potential doubling in the future HFO-1234yf emissions in China mainly affected the local TFA depositions. The TFA concentrations in rainwater were strongly affected by the regional precipitation rates. North Africa and the Middle East, regions with scant rainfall, had extremely high TFA concentrations. The rainwater concentrations of TFA during individual rain events can exceed the level considered to be safe, indicating substantial potential regional risks from future HFO-1234yf use.
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http://dx.doi.org/10.1021/acs.est.7b05960DOI Listing
March 2018

Effect and safety of cytokine-induced killer (CIK) cell immunotherapy in patients with breast cancer: A meta-analysis.

Medicine (Baltimore) 2017 Oct;96(42):e8310

Department of Medicine, Xijing University, Xi'an, Shaanxi Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, China.

Background: Breast cancer (BC) is considered a systemic disease with a primarily locoregional component. The accumulation of basic researches and clinical studies related to cytokine-induced killer (CIK) cells has confirmed their safety and feasibility in treating BC. By searching the PubMed, Embase, CNKI, and Wanfang databases, we conducted a meta-analysis to assess the efficacy and safety of DC/CIK plus chemotherapy regimen (Exp) compared with chemotherapy (Con) alone regimen for breast carcinoma. Studies were pooled, and the relative risk (RR) and its corresponding 95% confidence interval (CI) were calculated.

Methods: Eleven relevant articles were included in this meta-analysis. We observed that complete response (CR) (RR = 1.54, 95% CI: 1.09-2.19, Pheterogeneity = .994, I = 0%), partial response (PR) (RR = 1.33, 95% CI: 1.11-1.59, Pheterogeneity = .802, I = 0%) and overall response rate (ORR) (RR = 1.37, 95% CI: 1.20-1.57, Pheterogeneity = .619, I = 0%) in BC patients treatment with DC/CIK plus chemotherapy regimen was improved than that with chemotherapy alone. There was no difference in the incidence of leukopenia, thrombocytopenia, hair loss, nausea/vomiting, hepatic complications, and neurologic complications in BC patient's treatment with DC/CIK plus chemotherapy regimen and with chemotherapy alone.

Results: Compared to chemotherapy alone, DC/CIK plus chemotherapy treatment significantly increased CR, PR, and ORR; however, there was no difference between the safeties.

Conclusion: DC/CIK plus chemotherapy treatment may be a valuable new option for the treatment of breast carcinoma in women. The present study, therefore, provides valuable information to help physicians make treatment decisions for their patients with BC.
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http://dx.doi.org/10.1097/MD.0000000000008310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662403PMC
October 2017

Cooperative activation of cardiac transcription through myocardin bridging of paired MEF2 sites.

Development 2017 04;144(7):1235-1241

Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143-3120, USA

Enhancers frequently contain multiple binding sites for the same transcription factor. These homotypic binding sites often exhibit synergy, whereby the transcriptional output from two or more binding sites is greater than the sum of the contributions of the individual binding sites alone. Although this phenomenon is frequently observed, the mechanistic basis for homotypic binding site synergy is poorly understood. Here, we identify a bona fide cardiac-specific enhancer that is synergistically activated by homotypic MEF2 binding sites. We show that two MEF2 sites in the enhancer function cooperatively due to bridging of the MEF2C-bound sites by the SAP domain-containing co-activator protein myocardin, and we show that paired sites buffer the enhancer from integration site-dependent effects on transcription Paired MEF2 sites are prevalent in cardiac enhancers, suggesting that this might be a common mechanism underlying synergy in the control of cardiac gene expression .
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http://dx.doi.org/10.1242/dev.138487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399617PMC
April 2017

Down-regulation of hsa-miR-148b inhibits vascular smooth muscle cells proliferation and migration by directly targeting HSP90 in atherosclerosis.

Am J Transl Res 2017 15;9(2):629-637. Epub 2017 Feb 15.

Department of Urology, Guizhou Provincial People's Hospital Guiyang 550002, P. R. China.

The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are crucial pathological processes that are involved in atherosclerosis. Growing evidence suggests that microRNAs (miRNAs) play critical roles in VSMCs functions. Here, we analyzed the expression of four atherosclerosis-related miRNAs and found that hsa-miR-148b was significantly down-regulated in plaques from atherosclerotic patients compared to a healthy control group. The restoration of hsa-miR-148b function in cells transfected with a hsa-miR-148b mimicmarkedly inhibited VSMCs proliferation and migration compared to a hsa-miR-148b mimic control. Furthermore, we discovered that heat shock protein 90 (HSP90) was a direct target of hsa-miR-148b in VSMCs. Hsa-miR-148b suppressed HSP90 expression by directly binding its 3'-untranslated region (UTR). In addition, the expression of hsa-miR-148b was negatively correlated with the HSP90 mRNA levels in plaques of atherosclerotic patients. Interestingly, the overexpression of HSP90 partly abrogated the hsa-miR-148b-mediated inhibition of VSMCs proliferation and migration. Our study provides the first evidence that hsa-miR-148b has anti-proliferative and migratory functions by targeting HSP90 in VSMCs and may aidin the development of new biomarkers and potential therapeutic targets for atherosclerosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340697PMC
February 2017

Degradation of Fluorotelomer-Based Polymers Contributes to the Global Occurrence of Fluorotelomer Alcohol and Perfluoroalkyl Carboxylates: A Combined Dynamic Substance Flow and Environmental Fate Modeling Analysis.

Environ Sci Technol 2017 04 28;51(8):4461-4470. Epub 2017 Mar 28.

Department of Physical and Environmental Sciences, University of Toronto Scarborough , 1095 Military Trail, Toronto, Ontario M1C 1A4, Canada.

Using coupled dynamic substance flow and environmental fate models, CiP-CAFE and BETR-Global, we investigated whether the degradation of side-chain fluorotelomer-based polymers (FTPs), mostly in waste stocks (i.e., landfills and dumps), serves as a long-term source of fluorotelomer alcohols (FTOHs) and perfluoroalkyl carboxylates (PFCAs) to the global environment. The modeling results indicate that, in the wake of the worldwide transition from long-chain to short-chain products, in-use stocks of C8 FTPs will peak and decline afterward, while the in-use stocks of C6 FTPs, and the waste stocks of both FTPs will generally grow. FTP degradation in waste stocks is making an increasing contribution to FTOH generation, the bulk of which readily migrates from waste stocks and degrades into PFCAs in the environment; the remaining part of the generated FTOHs degrade in waste stocks, which makes those stocks reservoirs that slowly release PFCAs into the environment over the long run because of the low leaching rate and extreme persistence of PFCAs. Short-chain FTPs have higher relative release rates of PFCAs from waste stocks than long-chain ones. Estimates of in-use and waste stocks of FTPs were more sensitive to the selected lifespan of finished products, while those of the emissions of FTOHs and PFCAs were more sensitive to the degradation half-life of FTPs in waste stocks. Our preliminary calculations highlight the need for environmentally sound management of obsolete FTP-containing products into the foreseeable future.
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http://dx.doi.org/10.1021/acs.est.6b04021DOI Listing
April 2017

Emissions estimates of carbon tetrachloride for 1992-2014 in China.

Environ Pollut 2017 May 3;224:670-678. Epub 2017 Mar 3.

College of Environmental Sciences and Engineering, Peking University, Beijing 100871, China. Electronic address:

Discrepancies in emission estimates of carbon tetrachloride (CCl, CTC), between bottom-up and top-down methods, have been shown since the 1990s at both the global and regional scale. This study estimates the emissions of China from 1992 to 2014 based on emission functions and aggregated activity information given reasonable uncertainties. The results show that emissions increase from 7.3 Gg/yr (5.6-9.1 Gg/yr at 95% confidential interval) to 14.0 (9.1-19.5) Gg/yr with a growth rate of 6.7 (1.9-11.4) %/yr during 1992-2002 and then decrease to a minimum of 4.3 (1.9-8.0) Gg/yr in 2011. More than 54% of the emissions during 1992-2009 are from the process agents sector. The estimates are comparable with those of other studies and those in this study based on observations during 2011-2014 using the interspecies correlation method. China's contribution to global emissions increases from 7.5% to 19.5% during 1992-2009, but the contribution is reduced to 9.9% and 8.0% in 2010 and 2011, respectively, indicating the effectiveness of compliance with the Montreal Protocol and its subsequent Amendments and Adjustments, whereby CTC emissions are phased-out. The results of this study are beneficial for narrowing the gap between bottom-up estimates and top-down emission calculations of CTC in China.
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http://dx.doi.org/10.1016/j.envpol.2017.02.051DOI Listing
May 2017

Reduced E-cadherin facilitates renal cell carcinoma progression by WNT/β-catenin signaling activation.

Oncotarget 2017 Mar;8(12):19566-19576

Department of Urology, Guizhou Provincial People's Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, 550002, China.

Reduced expression of E-cadherin was observed in renal cell carcinoma (RCC). However, its potential clinical value and correlation with WNT/β-catenin signaling in RCC progression was still unclear. Immunohistochemical staining was performed in RCC tissue microarray to examine the expression status and prognosis value of E-cadherin and β-catenin. The potential role of E-cadherin in β-catenin translocation was analyzed with immunobloting assays. A significant negative correlation was observed between E-cadherin and β-catenin expression in RCC tissues. E-cadherin inhibits β-catenin translocation from membrane to cytoplasm in RCC tissues, which was an important step for WNT/β-catenin signaling. Reduced E-cadherin expression was associated with poor prognosis. More importantly, E-cadherin-/β-catenin+ was an independent detrimental factor for survival estimation of RCC patients. Reduced E-cadherin expression in RCC promoted cancer progression via WNT/β-catenin signaling pathway activation. E-cadherin/β-catenin provides a valuable prognosis marker for RCC, which may be an effective target for RCC therapy.
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http://dx.doi.org/10.18632/oncotarget.15361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386706PMC
March 2017

[CHANGE AND CLINICAL SIGNIFICANCE OF CERVICAL SPINE SAGITTAL ALIGNMENT OF ADOLESCENT IDIOPATHIC SCOLIOSIS].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2016 Mar;30(3):336-42

Objective: To investigate the changes and relationship of cervical spine sagittal alignment and other spinal-pelvic sagittal parameters in adolescent idiopathic scoliosis.

Methods: Between July 2011 and July 2014, 35 patients with idiopathic scoliosis who met the inclusion criteria underwent posterior pedicle screw instrumentation and fusion. There were 12 males and 23 females with a mean age of 16.2 years (range, 13-20 years), including 16 cases of Lenke type 1, 7 cases of Lenke type 2, 4 cases of Lenke type 3, 3 cases of Lenke type 4, 4 cases of Lenke type 5, and 1 case of Lenke type 6. The average follow-up time was 10.9 months (range, 5-36 months). The pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis (TK), cervical lordosis (CL), T1 slope, C2 slope, C7 sagittal vertical axis (C7 SVA), C2.7 plumbline (cSVA) were measured on pre- and post-operative standing lateral X-ray film. Based on preoperative CL, the patients were divided into kyphosis group (CL > 0 degress) and lordosis group (CL < 0 degrees); after operation, the patients were divided into restored lordosis (group A), decreased kyphosis (group B), and increased lordosis (group C) after operation. All data about sagittal profile changes were analyzed. The relations between CL and other spinal-pelvic parameters in the kyphosis and lordosis groups before operation were determined via Spearman correlation coefficient.

Results: Statistically significant changes were observed in PT, PI, SS, and LL between at pre- and post-operation (P < 0.05), but no significant difference was found in the other parameters (P > 0.05). There were 17 patients in lordosis group and 18 in kyphosis group before operation. Intra-group comparisons showed significant changes in PT, PI, SS, C2 slope, and C7 SVA in lordosis group, and in PT, PI, SS, LL, CL, TK, T1 slope, and C2 slope in kyphosis group (P < 0.05). Subgroup comparisons showed significant changes in CL, TK, C2 slope, C7 SVA, and T1 slope before operation (P < 0.05) and T1 slope at last follow-up between 2 groups (P < 0.05). In kyphosis group, 7 cases (group A) had restored lordosis, 7 cases (group B) had decreased kyphosis, and 4 cases had increased lordosis. In lordosis group, 9 cases (group C) had increased lordosis, 3 cases had decreased lordosis, and 5 cases had kyphotic cervical alignment after operation. Significant difference was found in LL, CL, T1 slope, C2 slope, and C7 SVA of group A, in TK and CL of group B, and in CL and cSVA of group C between pre- and post-operation (P < 0.05). There were significant differences in pre- and post-operative LL between groups A and B (P < 0.05). In lordosis group, there was a strong correlation between CL and C2 slope (P < 0.05) at preoperation. CL had strong correlation with C2 slope and T1 slope (P < 0.05) at pre-operation in kyphosis group, and CL had moderate correlation with cSVA (P < 0.05).

Conclusion: Cervical sagittal alignment plays an important role in the balance of the spine and pelvis. The change of cervical sagittal alignment has a certain correlation with the change of thoracic kyphosis. Attention to properly maintaining or restoring cervical sagittal lordosis alignment should be considered in preoperative evaluation of adolescent indiopathic scoliosis.
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March 2016

Modulation of tissue repair by regeneration enhancer elements.

Nature 2016 Apr 6;532(7598):201-6. Epub 2016 Apr 6.

Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.

How tissue regeneration programs are triggered by injury has received limited research attention. Here we investigate the existence of enhancer regulatory elements that are activated in regenerating tissue. Transcriptomic analyses reveal that leptin b (lepb) is highly induced in regenerating hearts and fins of zebrafish. Epigenetic profiling identified a short DNA sequence element upstream and distal to lepb that acquires open chromatin marks during regeneration and enables injury-dependent expression from minimal promoters. This element could activate expression in injured neonatal mouse tissues and was divisible into tissue-specific modules sufficient for expression in regenerating zebrafish fins or hearts. Simple enhancer-effector transgenes employing lepb-linked sequences upstream of pro- or anti-regenerative factors controlled the efficacy of regeneration in zebrafish. Our findings provide evidence for 'tissue regeneration enhancer elements' (TREEs) that trigger gene expression in injury sites and can be engineered to modulate the regenerative potential of vertebrate organs.
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http://dx.doi.org/10.1038/nature17644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844022PMC
April 2016

Long-term emissions of hexabromocyclododecane as a chemical of concern in products in China.

Environ Int 2016 May 19;91:291-300. Epub 2016 Mar 19.

College of Environmental Sciences and Engineering, Peking University, Beijing 100871, PR China.

There has been ever-increasing international interest in investigating the long-term emissions of chemicals in products (CiPs) throughout their entire life cycle in the anthroposphere. Hexabromocyclododecane (HBCDD) is a contemporary example of special interest due to the recent listing of this hazardous flame retardant in the Stockholm Convention and the consequent need for parties to take appropriate measures to eliminate this compound. Here, we conducted a scenario-based dynamic substance flow analysis, coupled with interval linear programming, to forecast the future HBCDD emissions in China in order to assist with the implementation of the Stockholm Convention in this current world's predominant HBCDD manufacturing and consuming country. Our results indicate that, under a business-as-usual scenario, the cumulative HBCDD production will amount to 238,000tonnes before its phase-out, 79% of which will be consumed in domestic market, accumulate as stocks in flame-retarded polystyrene insulation boards, and ultimately end up in demolition waste. While the production is scheduled to end in ca. 2021, emissions of HBCDD would continue until after 2100. For the entire simulation period 2000-2100, 44% of total cumulative emissions will arise from the industrial manufacture of HBCDD-associated end-products, whereas 49% will come from the end-of-life disposals of HBCDD-containing waste. The most effective end-of-life disposal option for minimizing emissions we found was, a pre-demolition screening combined with complete incineration. Our study warns of the huge challenges that China would face in its eliminating HBCDD contamination in the following decades, and provides an effective methodology for a wider range of countries to recognize and tackle their long-term emission problems of hazardous CiPs.
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http://dx.doi.org/10.1016/j.envint.2016.03.007DOI Listing
May 2016