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Dong-Feng Wu,1,* Dan Lin,2,* Feng Lu,1 Qin-Chen Liao,1 Yu-Juan Wu,1 Zhou Wang,1 Kun Yu,1 Wei-Jun Li,1 Jin-Long Deng1 1Department of the Geriatric Cardiology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, People’s Republic of China; 2Department of the First Comprehensive Clinic, The Affiliated Stomatology Hospital of Guangxi Medical University, Nanning 530021, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jin-Long Deng Department of the Geriatric CardiologyPeople’s Hospital of Guangxi Zhuang Autonomous Region, 6 Taoyuan Road, Nanning 530021, Guangxi, People’s Republic of ChinaEmail djl_gx@163.comBackground: Epidemiological studies have shown that there are sex differences in blood lipid levels and lipid responses to statins. Previous studies have shown that the rs5888 single nucleotide polymorphism (SNP) in the scavenger receptor class B type 1 (SCARB1) gene is associated with serum lipid levels in a sex-specific manner. The present study was undertaken to detect the sex-specific influence of the SCARB1 rs5888 SNP on the serum lipid response to atorvastatin in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).Methods: A total of 158 unrelated ACS patients (108 males, 50 females) were enrolled, and all patients received atorvastatin 20 mg/daily after PCI. Genotyping of the rs5888 SNP was performed by polymerase chain reaction and direct sequencing. Serum lipid profiles were determined before treatment and after an average follow-up time of one year.Results: The baseline serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo)AI levels were higher in females than in males (P< 0.05). After treatment with atorvastatin, serum TC, LDL-C, and ApoB were decreased, and ApoAI was increased (P< 0.05). The effects of atorvastatin on serum lipid levels were different between males and females, and females had greater decreases in TC, LDL-C and ApoB levels than males (P< 0.05). The genotypic frequencies of the rs5888 SNP were not different between males and females. The atorvastatin response was not associated with the rs5888 SNP in males (P > 0.05). Nonetheless, in female individuals carrying the rs5888 T-allele, we observed a greater reduction in TC, LDL-C, and ApoB levels after the use of 20 mg/day atorvastatin (P< 0.05).Conclusion: This study indicates that the SCARB1 rs5888 T-allele was associated with a greater reduction in serum TC, LDL-C, and ApoB after atorvastatin treatment in female patients with ACS undergoing PCI.Keywords: sex-specific, lipid, atorvastatin, scavenger receptor class B type 1, polymorphism, coronary artery disease

Mechanical hyperalgesia is a common and potentially disabling complication of many inflammatory and neuropathic conditions. Activation of the enzyme PKCε in primary afferent nociceptors is a major mechanism that underlies mechanical hyperalgesia, but the PKCε substrates involved downstream are not known. Here, we report that in a proteomic screen we identified the NaV1.8 sodium channel, which is selectively expressed in nociceptors, as a PKCε substrate. PKCε-mediated phosphorylation increased NaV1.8 currents, lowered the threshold voltage for activation, and produced a depolarizing shift in inactivation in wild-type - but not in PKCε-null - sensory neurons. PKCε phosphorylated NaV1.8 at S1452, and alanine substitution at this site blocked PKCε modulation of channel properties. Moreover, a specific PKCε activator peptide, ψεRACK, produced mechanical hyperalgesia in wild-type mice but not in Scn10a-/- mice, which lack NaV1.8 channels. These studies demonstrate that NaV1.8 is an important, direct substrate of PKCε that mediates PKCε-dependent mechanical hyperalgesia. [ABSTRACT FROM AUTHOR]

Introduction: EGFR-mutated NSCLC is characterized by an immunosuppressive microenvironment that confers limited clinical effectiveness to anti-PD-1 or PD-L1 antibodies. Despite the discouraging outcomes of immunotherapy, novel immune checkpoints are constantly emerging, among which the specific vulnerability for therapeutic intervention in the context of EGFR-mutated NSCLC remains unresolved., Methods: Data sets of patient- and cell line-levels were used for screening and mutual validation of association between EGFR mutation and a panel of immune checkpoint-related genes. Regulatory mechanism was elucidated through in vitro manipulation of EGFR signaling pathway and evaluated by immunoblot analysis, quantitative polymerase chain reaction, flow cytometry, immunofluorescence staining, and chromatin immunoprecipitation. In vivo investigation of different therapeutic strategies were conducted using both immunocompetent and immunodeficient mouse models., Results: Among all screened immune checkpoints, CD47 emerged as the candidate most relevant to EGFR activation. Mechanistically, EGFR mutation constitutively activated downstream ERK and AKT pathways to respectively up-regulate the transcriptional factors c-Myc and NF-κB, both of which structurally bound to the promotor region of CD47 and actively transcribed this "don't eat me" signal. Impaired macrophage phagocytosis was observed on introduction of EGFR-sensitizing mutations in NSCLC cell line models, whereas CD47 blockade restored the phagocytic capacity and augmented tumor cell killing in both in vitro and in vivo models. Remarkably, the combination of anti-CD47 antibody with EGFR tyrosine kinase inhibitor revealed an additive antitumor activity compared with monotherapy of either antitumor agent in both immunocompetent and adaptive immunity-deficient mouse models., Conclusions: EGFR-sensitizing mutation facilitates NSCLC's escape from innate immune attack through up-regulating CD47. Combination therapy incorporating CD47 blockade holds substantial promise for clinical translation in developing more effective therapeutic approaches against EGFR-mutant NSCLC., Competing Interests: Disclosure Dr. Wu is an employee of Shenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co., Ltd. The remaining authors declare no conflict of interest, (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Homocysteine (Hcy) is a sulphur-containing nonessential amino acid derived from the intermediate metabolites of methionine. Methionine is obtained from dietary proteins, such as poultry, meat, eggs, seafood, and dairy products. Abnormalities in Hcy metabolic pathways, deficiencies in dietary methionine, folate, and vitamins B12, B6, and B2 and genetic defects, polymorphisms, or mutations in Hcy metabolism-related enzymes may lead to an increase in plasma Hcy levels. Generally, a plasma Hcy level higher than 10 or 15 μmol/L has been defined as hyperhomocysteinemia (HHcy). An individual with essential hypertension complicated with HHcy is considered to have H-type hypertension (HTH). Currently, HHcy is considered a novel independent risk factor for various cardiovascular diseases. To provide a useful reference for clinicians, the research progress on Hcy, HHcy, and HTH in recent years was systematically reviewed here, with a focus on the source and metabolic pathways of Hcy, plasma Hcy levels and influencing factors, detection methods for plasma Hcy levels, relationship between Hcy concentration and hypertension, pathogenesis of HTH, cardiovascular complications of HTH, and treatment of HTH., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age., Methods: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up., Results: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple + infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found., Conclusion: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings., Clinical Trial Registration: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Wastewater-based epidemiology (WBE) is an objective approach for the estimation of population-level exposure to a wide range of substances, in which the use of a population biomarker (PB) could significantly reduce back-calculation errors. Although some endogenous or exogenous compounds such as cotinine and other hormones have been developed as PBs, more PBs still need to be identified and evaluated. This study aimed to propose a novel method to estimate population parameters from the mass load of metal ion biomarkers in wastewater, and estimate the consumption of tobacco in 24 cities in Southern China using the developed method. Daily wastewater samples were collected from 234 wastewater treatment plants (WWTPs) in 24 cities in Southern China. Atomic absorption spectroscopy (AAS) was applied to determine the concentrations of common health-related metal ions in wastewater, including sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), iron (Fe), and zinc (Zn), and compared them with the daily mass load of cotinine corresponding to catchment populations. The concentrations of cotinine in wastewater samples were measured using liquid chromatography-tandem mass spectrometry. There were clear and strong correlations between the target metal ion equivalent population and census data. The correlation coefficients (R) were R K  = 0.78, R Na  = 0.66, R Ca  = 0.81, R Mg  = 0.77, and R Fe  = 0.69, at p < 0.01 and R 2  > 0.6. Subsequently, the combination of WBE and metal ion PBs was used to estimate tobacco consumption. Daily consumption of nicotine was estimated to be approximately 1.76 ± 1.19 mg/d/capita, equivalent to an average of 13.0 ± 8.75 cigarettes/d being consumed by smokers. The data on tobacco consumption in this study were consistent with those in traditional surveys in Southern China. The metal ion potassium is an appropriate PB for reflecting the real-time population and could be used to evaluate the tobacco consumption in WBE study., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Aim: To evaluate trends in glaucoma procedures at the Peking University Eye Center in 2016-2020., Methods: A retrospective search of all glaucoma procedures performed at our institution were performed. Data were analyzed by calculating the absolute numbers and relative weightage of each procedure per year., Results: The average age of glaucoma patients undergoing surgical procedures was 62.33±17.87y, and 55% were women. From 2016 to 2019, the number of surgical procedures performed in glaucoma patients showed an overall upward trend from 749 to 1460, although it decreased slightly in 2020 ( n =1393), probably due to the COVID-19 pandemic. The number of trabeculectomies did not change significantly in 2016 ( n =161) to 2018 ( n =164) but decreased in 2019 ( n =139) to 2020 ( n =121), indicating a reduction in its relative weightage among glaucoma procedures (from 21.50% to 8.69%). The number of glaucoma drainage device implantations and minimally invasive glaucoma surgeries both increased (50 and 58 respectively in 2019), except in 2020. The number of transscleral cyclophotocoagulation procedures was relatively stable, increasing until 2017 ( n =218) and then decreasing. Cataract surgeries with or without glaucoma procedures accounted for a large number of the total surgeries, increasing from 247 (32.97%) in 2016 to 967 (69.42%), among which cataract extraction combined with goniosynechialysis was the most frequent., Conclusion: The overall increase in the number of operating room-based surgical procedures is significant. Trabeculectomy is one of the most commonly performed procedures, despite the relative decline in its weightage. Other procedures, including use of glaucoma drainage devices and mini shunts and minimally invasive glaucoma surgeries, are gaining greater acceptance. Notably, lens-related surgery plays an important role in glaucoma management., (International Journal of Ophthalmology Press.)

This study aimed to investigate the differential effects of hyperhomocysteinemia (HHcy) on lipid profiles and lipid ratios between patients with coronary artery disease (CAD) and without CAD. The data of 872 CAD patients and 774 non-CAD controls were extracted from the information system of hospitalized patients. Serum homocysteine (Hcy), total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI, and ApoB concentrations were detected. HHcy was defined as a serum level of Hcy ≥ 15 μmol/L. The CAD patients had lower levels of HDL-C and ApoAI and higher levels of Hcy than the controls (P < .05). Serum TGs and HDL-C were negatively correlated with Hcy in controls. Serum HDL-C and ApoAI were negatively correlated with Hcy, and the ratios of TC/HDL-C, TG/HDL-C, LDL/HDL-C, and ApoB/ApoAI were positively correlated with Hcy in the CAD patients (P < .05). Although the trends for HHcy to decrease the lipid profiles were not different between the CAD and controls (Pinteraction > 0.05), CAD with HHcy had lower HDL-C and ApoAI levels than those of subjects with normal Hcy; controls with HHcy had lower TC, LDL-C, and ApoB levels than those of subjects with normal Hcy (P < .05). There were different HHcy trends affecting the ratios of TC/HDL-C and LDL/HDL-C between the CAD patients and controls (Pinteraction for TC/HDL-C = 0.025; Pinteraction for LDL/HDL-C = 0.033). CAD patients with HHcy had a higher ratio of TC/HDL-C (P = .022) and LDL/HDL-C (P = .045) than those of patients with normal Hcy, but in the controls, the subjects with HHcy exhibited a trend toward a decreased ratio of TC/HDL-C (P = .481) and LDL/HDL-C (P = .303). There were differential effects of HHcy on the lipid ratios between CAD and non-CAD patients. HHcy was related to higher ratios of TC/HDL-C and LDL/HDL-C in patients with CAD., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Previous studies have demonstrated that REBACIN ® intervention eliminates persistent high-risk human papillomavirus (hrHPV) infection. The initial establishment and subsequent progression of cervical cancer mainly depends on two major oncogenes, E6/E7, and previous studies have proposed E6/E7 oncogenes as a target for therapeutic drug development. The aim of this study was to investigate in vitro and in vivo whether REBACIN ® inhibits E6/E7 oncogenes for elucidating the mechanism of REBACIN ® in the clearance of persistent hrHPV infection. In vitro , after REBACIN ® treatment, the growth of both Ca Ski and HeLa cervical cancer cells containing the E6/E7 oncogenes was prevented. In line with this finding is that E6/E7 expression was inhibited, which can be counteracted by the co-application of anti-REBACIN ® antibody. These studies demonstrated that REBACIN ® can effectively inhibit the growth of cervical cancer cells via targeting HPV E6/E7 expression. To further verify this finding in clinic, 108 volunteer patients with persistent hrHPV infections were randomly divided into REBACIN ® , recombinant human interferon alpha-2b (Immunological drug control), or no-treatment blank control groups, received intravaginal administration of REBACIN ® , interferon or no-treatment every other day for three months, and then followed up for E6/E7 mRNA assay. In REBACIN ® group, 68.57% of patients showed complete clearance of HPV E6/E7 mRNA, which was significantly higher compared to 25.00% in the interferon immunological drug control group and 20.00% in blank control group, confirming that REBACIN ® is potently efficacious on clearing persistent hrHPV infections via inhibition of HPV E6/E7 oncogenes., Clinical Trial Registration: http://www.chictr.org.cn/historyversionpuben.aspx?regno=ChiCTR2100045911, identifier ChiCTR2100045911., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Wu, Yao, Zhang, Tian, Chen and Zhang.)

Ambroxol is a commonly used mucolytic agent principally used to treat respiratory diseases, which may have a role as adjunctive therapy for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but there is lack of evidence about its effectiveness on coronavirus disease-2019 (COVID-19) patients. To study the association between ambroxol use and clinical outcomes among hospitalized patients of COVID-19 infection. We conducted a multicenter retrospective cohort study involving 3,111 patients with confirmed SARS-CoV-2 infection from three hospitals in Wuhan from 19 December 2019 to 15 April 2020, and the primary outcome was in-hospital mortality. COVID-19 patients were classified into ambroxol and non-ambroxol groups based on the administration of ambroxol during hospitalization. Two analyses including propensity score matching (PSM) to obtain a 1:1 balanced cohort and logistic regression were used to control for confounding factors. The average age of 3,111 patients was 57.55 ± 14.93 years old, 127 of them died during hospitalization, and 924 of them used ambroxol. Treatment with ambroxol did not have a significant effect on in-hospital mortality of COVID-19 patients when compared with non-ambroxol in PSM model after adjusting for confounders (8.0% vs. 3.5%, adjusted OR, 1.03 [95% CI, 0.54-1.97], p  = 0.936). Adverse events such as nausea/vomiting, headache, and rash were comparable between the two groups. Our results suggest that the use of ambroxol is not significantly associated with in-hospital mortality in COVID-19 patients, which provides evidence for evaluating the effects of ambroxol on COVID-19 patient outcomes and may be helpful for physicians considering medication alternatives for COVID-19 patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lu, Yang, Zhuo, Yang, Kou, Gao, Hu, Jiang, Li, Wu, Sun, Cheng and Zhan.)

Objective: This study aimed to describe our experience of managing cesarean scar pregnancy (CSP) and outcomes depending on ultrasound imaging features., Methods: A retrospective, cohort observational study was performed on 31 consecutive patients with CSP at 6 to 9 weeks of gestation from April 2015 to January 2021. All patients were evaluated for the residual myometrial thickness (RMT), growth direction of the gestational sac (GS), blood flow, and chorionic parenchyma using ultrasonography. Patients underwent curettage or methotrexate (MTX) combined with curettage in CSP depending on the age of the GS. Blood loss of >500 mL with curettage was considered major bleeding., Results: Twenty-five (80.6%) patients had successful treatment, and six (19.4%) patients had major bleeding. The incidence of major bleeding was significantly higher in patients with >7 weeks of gestation, types II and III CSP, mixed and exogenous types of the growth direction of the GS, an RMT < 2 mm, and multiple lacunae formation in thickened chorionic parenchyma., Conclusions: The exogenous and mixed types of the GS, an RMT < 2 mm, and multiple lacunae in thickened chorionic parenchyma may be high-risk factors for major hemorrhage by curettage in CSP.

Using Na-encapsulated benzo[18]crown-6 (Na)(B18C6) as a counter cation, we successfully magnetically isolated a fluoride-bridging Dy dinuclear complex {[(PW 11 O 39 )Dy(H 2 O) 2 ] 2 F} (Dy 2 POM) with lacunary Keggin ligands. (Na)(B18C6) formed two types of tetramers through C-H⋯O, π⋯π and C-H⋯π interactions, and each tetramer aligned in one dimension along the c -axis to form two types of channels. One channel was partially penetrated by a supramolecular cation from the ± a -axis direction, dividing the channel in the form of a "bamboo node". Dy 2 POM was spatially divided by this "bamboo node," which magnetically isolated one portion from the other. The temperature dependence of the magnetic susceptibility indicated a weak ferromagnetic interaction between the Dy ions bridged by fluoride. Dy 2 POM exhibited the magnetic relaxation characteristics of a single-molecule magnet, including the dependence of AC magnetic susceptibility on temperature and frequency. Magnetic relaxation can be described by the combination of thermally active Orbach and temperature-independent quantum tunneling processes. The application of a static magnetic field effectively suppressed the relaxation due to quantum tunneling., Competing Interests: We have no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Shrubs are the major components of vegetation in arid and semi-arid areas, and play a pivotal role in maintaining ecosystem stability and function. The nurse effects of shrubs can help with the regeneration of native target plant species by alleviating the adverse influences that limit their growth and reproduction in degraded habitats. We summarized the main research results and application of shrub nurse effects in the last 20 years. We discussed several facilitation mechanisms of nurse shrubs, including microhabitat amelioration, fertile island formation, defense and resistance against herbivores, introduction of beneficial microorganism and propagule propagation or preservation, as well as changes in the patterns of interspecific competitive networks. Key factors affecting nurse effects were analyzed, including abiotic environments, biological disturbances, plant life history as well as growth and reproductive strategies. Prospects for future research were also considered from the aspects of improving theore-tical mechanisms of nurse effects by shrubs and building models involved in multiple plant species interaction affec-ted by multifactors.

Objective: To assess the influencing factors of transtemporal window quality and identify patients suitable for transcranial sonography (TCS) examination in two-dimensional imaging., Methods: In this cross-sectional study, TCS was performed in 161 consecutive patients through the temporal bone window (TBW) in the neurology or neurosurgery department. Each patient's sex, age, height, weight, and temporal bone thickness (TBT) were collected. After examination, the patients were divided into two groups: TBW success and TBW failure. The data were statistically compared between the two groups., Results: Among the studied population, the total TBW success rate was 80.1% (95% confidence interval [CI]: 74-86). The TBW success rate was 91.4% (95% CI: 85-98) in males and 70.9% (95% CI: 61-81) in females (p = .001). Sex (p = .001), age (p = .002), height (p = .047), and TBT (p < .001) showed significant differences between the TBW success and failure groups. In males, only TBT (p = .001) showed a significant difference; in females, age (p < .001) and TBT (p = .003) showed a significant difference. The area under the receiver operating characteristic curve (AUC) of sex, age, and TBT and their combination was 0.686, 0.659, 0.842, and 0.922 (p < .001), respectively. The AUC of the combination of parameters was significantly greater than that of age and sex alone (p = .007; p = .0002) but not greater than that of TBT (p = .090)., Conclusions: The TBW success rate varied with sex, age, height, and TBT. Males, younger patients, taller patients, and patients with a thinner temporal bone tended to be more suitable for the examination by TCS., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Fentanyls abuse is a persistent international concern. New fentanyl derivatives are constantly appearing, circumventing national and international laws. In this study, laboratory degradation experiment with different conditions such as pH, light, temperature and oxygen availability were compared to improve the understanding of the fentanyls degradation pathways. Twelve major degradants of sufentanil and alfentanil were detected and identified together using UHPLC-QTOF-MS. A total of thirty nine fentanyls including twelve typical fentanyl new psychoactive substances, eighteen manufacturing process-related substances and nine key degradants of sufentanil and alfentanil were screened in 120 sewage water samples collected from 20 sewage water treatment plants chosen among 6 urban cities in east China from July to August in 2020 using a validated UHPLC-MS/MS method. Three fentanyls (fentanyl, sufentanil, alfentanil), seven degradants and six manufacturing process-related substances were found in the test samples. The study could provide a useful tool for the monitoring of the abuses, illegal manufacturing or pharmaceuticals related pollutions of fentanyls and their analogs., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Background: Protein phosphatase 2 regulatory subunit B'' alpha ( PPP2R3A ) gene has been reported in other tumors, but the influence of PPP2R3A gene expression on the occurrence, development, and prognosis of hepatocellular carcinoma (HCC) remains unclear., Aim: To investigate whether the PPP2R3A gene could be used to predict tumor recurrence and survival of HCC patients after liver transplantation (LT)., Methods: Diseased liver tissues of HCC patients after LT were collected as well as their clinical data and follow-up information. The immunohistochemical method was used to detect the expression of PPP2R3A protein in the tissues of 108 patients with primary liver cancer. The χ 2 test was used to analyze the relationship between PPP2R3A protein expression levels and the clinicopathological features of tumors. The Kaplan-Meier method was used to analyze overall postoperative survival. The COX proportional hazard model was used to analyze adverse prognostic factors., Results: Immunohistochemistry showed that the PPP2R3A protein was mainly expressed in the cytoplasm of HCC cells. Compared to corresponding peritumoral tissues, expression was higher in HCC tissues ( P ≤ 0.001). Correlation analysis showed that high PPP2R3A expression was correlated with preoperative serum alpha-fetoprotein (AFP) levels ( P = 0.003), tumor-node-metastasis-t stage ( P ≤ 0.001), and envelope invasion ( P = 0.001). Univariate analysis showed that overall survival ( P ≤ 0.001) and recurrence-free survival ( P = 0.025) of patients with high PPP2R3A expression (≥ 4 points) were poor compared to those with low expression (< 4 points). The overall survival rates or recurrence-free survival rates at 1, 2, and 3 years with high PPP2R3A expression were 73%, 38%, and 23% or 31%, 23%, and 23%, respectively. Multivariate analysis showed that high PPP2R3A expression (hazard ratio = 2.900, 95% confidence interval: 1.411-5.960, P = 0.004) was an independent survival risk factor of HCC patients after LT, and it was also an independent predictor of postoperative tumor recurrence. This study also showed in patients with AFP ≥ 400 ng/mL, the overall survival ( P ≤ 0.001) and recurrence-free survival ( P = 0.023) of those with high PPP2R3A expression were significantly worse compared to those with low PPP2R3A expression. When PPP2R3A expression was low, the overall survival rate ( P = 0.461) or recurrence-free survival rate ( P = 0.072) after LT in patients with AFP < 400 ng/mL and ≥ 400 ng/mL was not significantly difference. The 1, 2, and 3 year survival rate of patients with low PPP2R3A expression and AFP < 400 ng/mL were 98%, 80%, and 69%, respectively, while patients who met Hangzhou criteria had a post-transplant 1, 2, and 3 years overall survival rate of 89%, 66%, and 55%, respectively., Conclusion: High expression of PPP2R3A might be a potential marker for predicting poor prognosis of HCC after LT. Combined with serum AFP levels, PPP2R3A might enhance the accuracy of predicting HCC outcome in patients after LT and supplement the efficacy of the Hangzhou criteria., Competing Interests: Conflict-of-interest statement: The authors have no any conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: High-density lipoprotein (HDL) plays an antiatherogenic role by mediating reverse cholesterol transport (RCT), antioxidation, anti-inflammation, and endothelial cell protection. Recently, series of evidence have shown that HDL can also convert to proatherogenic HDL under certain circumstances. Plasma paraoxonase 1 (PON1) as an HDL-bound esterase, is responsible for most of the antioxidant properties of HDL. However, whether PON1 can serve as a therapeutic target of dysfunctional HDL-related atherosclerosis remains unclear., Methods: In this study, scavenger receptor class B type I deficient ( Scarb1 -/- ) mice were used as the animal model with dysfunctional HDL and increased atherosclerotic susceptibility. Hepatic PON1 overexpression and secretion into circulation were achieved by lentivirus injection through the tail vein. We monitored plasma lipids levels and lipoprotein profiles in Scarb1 -/- mice, and measured the levels and activities of proteins associated with HDL function. Meanwhile, lipid deposition in the liver and atherosclerotic lesions was quantified. Hepatic genes relevant to HDL metabolism and inflammation were analyzed., Results: The results showed the relative levels of PON1 in liver and plasma were increased by 1.1-fold and 1.6-fold, respectively, and mean plasma PON1 activity was increased by 63%. High-level PON1 increased the antioxidative and anti-inflammatory properties, promoted HDL maturation and macrophage cholesterol efflux through increasing HDL functional proteins components apolipoprotein A1 (APOA1), apolipoprotein E (APOE), and lecithin-cholesterol acyltransferase (LCAT), while decreased inflammatory protein markers, such as serum amyloid A (SAA), apolipoprotein A4 (APOA4) and alpha 1 antitrypsin (A1AT). Furthermore, hepatic PON1 overexpression linked the effects of antioxidation and anti-inflammation with HDL metabolism regulation mainly through up-regulating liver X receptor alpha (LXRα) and its downstream genes. The pleiotropic effects involved promoting HDL biogenesis by raising the level of APOA1, increasing cholesterol uptake by the liver through the APOE-low density lipoprotein receptor (LDLR) pathway, and increasing cholesterol excretion into the bile, thereby reducing hepatic steatosis and aorta atherosclerosis in Western diet-fed mice., Conclusions: Our study reveals that high-level PON1 improved dysfunctional HDL and alleviated the development of atherosclerosis in Scarb1 -/- mice. It is suggested that PON1 represents a promising target of HDL-based therapeutic strategy for HDL-related atherosclerotic cardiovascular disease., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-682). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Rationale: Fentanyl and its analogues play important roles in the hospital and clinic setting as anesthetics. However, illicitly manufactured fentanyl as well as the new psychoactive substances (NPS) account for 30% of all deaths in the United States. Since fentanyl derivatives and NPS are designed to produce similar effects, their related substances are similar or even have the same active groups. A comprehensive analysis of the related substances of alfentanil hydrochloride can provide a basis for the identification and supervision of fentanyl derivatives and NPS., Methods: A liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (LC/QTOF-MS/MS) method was developed for the separation and characterization of related substances in alfentanil hydrochloride. Degradation studies were conducted according to the ICH-prescribed stress conditions. The compounds were identified mainly through positive electrospray ionization QTOF high-resolution mass spectrometric measurements of the accurate masses of the precursor and product ions and their calculated elemental compositions. Their formation mechanisms were also discussed., Results: Seventeen related substances were detected in alfentanil hydrochloride and its stressed samples. Among them, nine were process-related substances and the other eight were degradation products. The stress study results demonstrated that alfentanil hydrochloride was unstable under acid, alkaline, and oxidative stress conditions, while relatively stable under dry photolytic and thermal stress conditions. Alfentanil hydrochloride was most susceptible for degradation at the N-phenylpropanamide and piperidine sites., Conclusions: Process-related alfentanil hydrochloride compounds are useful for determination of synthetic routes and entangling of fentanyl analogues. The stress study results can provide a sound scientific basis for the waste water monitoring of alfentanil. These results are important for routine quality control in the manufacturing and storage of alfentanil hydrochloride, as well as for drug enforcement of fentanyl and its analogues., (© 2020 John Wiley & Sons, Ltd.)

In mammals, the excretion of cortisol can provide energy toward restoring homeostasis and is a major component of the stress response. However, chronically elevated cortisol levels also have suppressive effects on immune function. As mounting an immune response is energetically costly, sick individuals may conserve energy by exhibiting certain sickness behaviors, such as declining activity levels. Due to the complex interplay between immune function and sickness behaviors, endocrinological correlates have received growing attention in the medical community, but so far, this subject was investigated rarely. Furthermore, given the complexities of studying illnesses and immunity in natural settings, correlates of sickness behaviors have yet to be studied in non-human primates in the wild. Methods: We measured urinary cortisol levels using liquid chromatography-mass spectrometry in a group of wild habituated chimpanzees in Taï National Park, Côte d'Ivoire, before, during, and after a respiratory disease outbreak (main causative pathogen: human respiratory syncytial virus A, with coinfections of Streptococcus pneumoniae ). Changes in cortisol levels were then related to urinary neopterin levels, a biomarker of immune system activation. Results: Urinary cortisol levels were found to be more than 10-fold higher during the outbreak in comparison with levels before and after the outbreak period. Increasing cortisol levels were also associated with increasing neopterin levels. Interestingly, rather atypical patterns in a diurnal decline of cortisol levels were found during infection periods, such that levels remained raised throughout the day. Conclusion: In conclusion, cortisol increase was related to cellular immune response. Our results suggest that cortisol is a mediator of infectious disease pathogenicity through its impact on the immune system and that wild chimpanzees may be facing energetic stress when sick. By monitoring immune challenges in wild-living animals, our study demonstrates that immune defenses have costs and that these costs are context-specific., (Copyright © 2020 Behringer, Preis, Wu, Crockford, Leendertz, Wittig and Deschner.)

A coronary artery fistula (CAF) is an abnormal connection between a coronary artery and any of the four cardiac chambers, the large vessels, or other vascular structures. Wellens syndrome is an ST-segment elevation myocardial infarction equivalent. Although both Wellens syndrome and CAFs have been reported in the literature, they have rarely been reported in the same patient. We herein report a case clinically diagnosed as Wellens syndrome by electrocardiography (ECG) findings; coronary angiography subsequently showed a fistula originating from the left anterior descending artery and draining into the pulmonary artery. The ECG findings then returned to normal after the fistula had been closed by controlled-release coils. These events confirmed that the abnormal ECG findings of Wellens syndrome were due to the CAF.

A family of new dinuclear lanthanide complexes as the simplest entities showing intramolecular magnetic interactions, [Ln2(dbm)2(L)2(CH3OH)2] (Ln = Tb (1), Dy (2), Ho (3), Er (4), Yb (5), Lu (6)), [Ln2(acac)2(L)2(EtOH)2] (Ln = Dy (7), Er (8)), [Dy2(TTA)2(L)2(CH3OH)2]·2CH2Cl2 (9) and [Dy2(tfa)2(L)2(CH3OH)2] (10) (H2L = N'-(2-hydroxy-5-methylphenyl)-pyrazine-2-carbohydrazide, Hdbm = 1,3-diphenyl-1,3-propanedione, Hacac = acetylacetone, HTTA = 2-thenoyltrifluoroacetone, Htfa = trifluoroacetylacetone), were constructed successfully by the reaction of a Schiff base ligand H2L and four different β-diketonate salts. As for complexes 4, 5 and 8, all exhibit the characteristic emission peaks of the corresponding Er3+, Yb3+ and Er3+ ions, respectively. Meanwhile, the excitation wavelength (510 nm) of 5 is located in the visible region, confirming its significant potential application value. Magnetic studies indicate that complexes 9 and 10 exhibit characteristic slow relaxation of magnetization with the energy barriers (Ueff) of 102 K for 9 and 140 K for 10 under a zero dc field. Under the optimized dc fields, slow magnetic relaxations are present in 2 and 7, and the Ueff values of 9 and 10 have been improved. This proves that the β-diketonate co-ligands deserve an important role in regulating Dy-SMMs influenced by the diverse perturbations of the axial crystal field originating from minor changes in the coordination environment.

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

Objective: The present study investigated whether changes in serum homocysteine (Hcy) levels modify the effects of atorvastatin treatment on blood lipid parameters in patients with acute coronary syndrome (ACS)., Methods: A total of 159 patients with ACS who received regular, long-term treatment with 20 mg/d atorvastatin were included. Depending on the changes in Hcy parameters, they were divided into Hcy reduction (HR) and Hcy elevation (HE) groups., Results: After long-term atorvastatin treatment, total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) B, and Hcy levels were decreased ( P < .05), and the ApoAI level was increased ( P < .01). Correlation and stratified analysis showed that Hcy or hyperhomocysteinemia was correlated with blood lipids. In both the HE and HR groups, the TC, LDL-C, and ApoB levels after treatment were lower than those before treatment ( P < .01), and the ApoAI level was increased compared with that before treatment ( P < .05). There was no difference in the reduction of TC, LDL-C, and ApoB levels or in the increase of ApoAI level ( P interaction > .05) between the 2 groups. However, there was a clear opposite trend of the effect of atorvastatin on TG and high-density lipoprotein cholesterol (HDL-C) levels between the HR and HE groups ( P interaction < .05). In the HR group, the HDL-C level was increased ( P < .05), and TGs were decreased compared with those before treatment ( P < .01). Nevertheless, in the HE group, the HDL-C level was decreased ( P < .05), and TGs ( P < .05) were increased compared with those before treatment., Conclusion: The effects of atorvastatin on TGs and HDL-C depend on changes in Hcy levels. Patients with a reduced Hcy level after atorvastatin treatment had more favorable lipid parameters.

The differences in the mechanism of cadmium (Cd) accumulation in the grains of different wheat (Triticum aestivum L.) cultivars remain unclear. Thus, we conducted a hydroponic experiment in a greenhouse to compare root surface adsorption, root uptake, subcellular distribution, and chemical forms of Cd between low- and high-Cd-accumulating wheat cultivars at seedling stage, to improve our understanding of the differences between cultivars. The results showed that Cd adsorbed on the root surface was mainly in a complexed form, and the total amount of Cd on the Yaomai16 (YM, high-Cd-accumulating genotypes) root surface was higher (p < 0.05) than that on Xinmai9817 (XM, low-Cd-accumulating genotypes). A large amount of Cd ions adsorbed on root surface would cause plant damage and inhibit growth. Comparing the root-to-shoot translocation factors of Cd, the transfer coefficients of YM were 1.017, 1.446, 1.464, and 1.030 times higher than those of XM under 5, 10, 50, and 100 μmol L -1 Cd treatments, respectively. The subcellular distribution of Cd under Cd exposure is mainly in the cell wall and soluble fraction. The proportions of Cd in YM shoot soluble fraction were higher than those in XM, which was the main detoxification mechanism limiting the activity of Cd and may be responsible for low Cd accumulation in grains, while the effects of the chemical forms of Cd on migration and detoxification were not found to be related to Cd accumulation in the kernels.

Pathogenic Escherichia coli (E. coli) is the most common pathogen causing urinary tract infection in animals. We investigated the antibiotic resistance and virulence genes of pathogenic E. coli CCHTP derived from urine with occult blood of the giant panda by whole genome sequencing. The flanking sequencing of resistance and virulence genes in genomic islands were also analyzed. Our results demonstrate that E. coli CCHTP contains different families of antibiotic resistance genes, most of which are efflux pump related genes, including multiple drug resistance efflux pump genes mdf A, emr E, and mdt N. A total of 166 virulence factors and 563 virulence genes were identified, and the most virulence factors and related genes are involved in host cell attachment and invasion processes. Furthermore, sequence analysis of 19 genomic islands revealed that antibiotic and virulence genes are associated with mobile genetic elements (transposon and insertion sequence) in GIs011 and GIs017. These structures can mediate horizontal transfer of antibiotic and virulence genes. Our work described the distribution of antibiotic resistance genes and virulence genes in E. coli CCHTP, which may provide an important guidance for treatment and rational drug use of E. coli CCHTP infection in the giant panda.

The development of highly sensitive HPV-genotyping tests has opened the possibility of treating HPV-infected women before high-grade lesions appear. The lack of efficient intervention for persistent high-risk HPV infection necessitates the need for development of novel therapeutic strategy. Here we demonstrate that REBACIN®, a proprietary antiviral biologics, has shown potent efficacy in the clearance of persistent HPV infections. Two independent parallel clinical studies were investigated, which a total of 199 patients were enrolled and randomly divided into a REBACIN®-test group and a control group without treatment. The viral clearance rates for the REBACIN® groups were 61.5% (24/39) and 62.5% (35/56), respectively, for the two independent parallel studies. In contrast, the nontreatment groups showed self-clearance rates at 20.0% (8/40) and 12.5% (8/64). We further found that REBACIN® was able to significantly repress the expression of HPV E6 and E7 oncogenes in TC-1 and Hela cells. The two viral genes are well known for the development of high-grade premalignancy lesion and cervical cancer. In a mouse model, REBACIN® was indicated to notably suppress E6/E7-induced tumor growth, suggesting E6 and E7 oncogenes as a potential target of REBACIN®. Taken together, our studies shed light into the development of a novel noninvasive therapeutic intervention for clearance of persistent HPV infection with significant efficacy., (© 2019 UICC.)

Objective: To compare the observation of high-grade glioma (HGG) based on intraoperative multiplane ultrasonography (US) images and preoperative reconstructive coplanar T1-weighted enhanced magnetic resonance imaging (MRI) using volume navigation (V Nav) fusion image technology., Methods: We retrospectively evaluated intraoperative data obtained from 16 patients diagnosed with HGG (grade III and IV). Overall, 18 nodules observed in 15 patients were examined. HGG images from US and contrast-enhanced US (CEUS) were compared with those from preoperative reconstructive coplanar enhanced T1-weighted MRI using automatic V Nav fusion image technology., Results: All HGG tumors were detected. Images of 13 of 18 tumors (72.2%) with obscure margins using B-mode US were improved with clear tumor boundaries using CEUS imaging. The relative difference in tumor area between CEUS and enhanced MRI modalities in 14 mainly solid component lesions was considered statistically significant (P value < 0.05). There was a perfect correlation of the enhanced area between coplanar CEUS and enhanced MRI., Conclusions: The V Nav fusion image system combining intraoperative real-time US imaging with reconstructive preoperative coplanar MRI is valuable for image-guided HGG resection. It is suitable for neurosurgeons who lack the expertise in US technology to discern the brain structure and allows better recognition of tumor and edema tissues compared with reconstructive preoperative coplanar-enhanced MRI in real time and in multiplane from different angles. In addition, CEUS combined with B-mode US could improve tumor detection and resection control in neurosurgery, even in single US-guided operations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

It remains a real challenge to treat the industrial wastewater containing hardly-decomposed dyes and heavy metal ions. Herein, an environment-friendly hybrid hydrogel is prepared by a simple mixing of selenocarrageenan (SeCA) and graphene oxide (GO) under heating and stirring for 5 min without any other reagent. Such a selenocarrageenan hybrid graphene hydrogel (SeCA-GH) without volume shrinkage exhibits excellent adsorption capacity and selective binding to dyes and Hg 2+ . The maximum adsorption capacity of methylene blue and Hg 2+ on SeCA-GH is 168 mg g -1 and 331 mg·g -1 at 25 °C, respectively. Furthermore, the adsorption characteristics of SeCA-GH are investigated in detail, including saturated adsorption capacity, adsorption isotherm, and kinetic adsorption process. Notably, SeCA-GH can be easily regenerated and reused for multiple cycles without release of SeCA and GO. SeCA-GH as recyclable adsorbent offers a promising candidate for sustainable, affordable, and efficient removal of dyes and Hg 2+ in water environment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Six phenoxo-O bridged dinuclear lanthanide(iii) complexes have been assembled utilizing the 2-[(4-nitrophenyl)imino]methyl-8-hydroxyquinoline (HL) and dibenzoylmethane (Hdbm) ligands: [Ln2(dbm)4L2] (Ln = Nd (1), Eu (2), Gd (3), Tb (4), Dy (5) and Er (6)). Complexes 1 and 6 exhibit the characteristic emission peaks of the corresponding Nd3+ and Er3+ ions, respectively. Meanwhile, the excitation wavelength (470 nm) for complex 1 is located in the visible-light region, confirming a practical application value. The studies on magnetic properties reveal that complex 3 features a magnetocaloric effect with a magnetic entropy change of -ΔSm = 14.36 J kg-1 K-1 at 4 K for ΔH = 7 T. What's more, the dynamic magnetic studies for complex 5 show that it exhibits slow magnetic relaxation behavior, typical of SMM behavior, resulting in an energy barrier of ΔE/kB = 75 K with the pre-exponential factor τ0 = 2.2 × 10-7 s. Meanwhile, this research demonstrates that the magnetic properties can be modulated by regulating the electron-donating/withdrawing effects of the substituents on the ligands.

Objectives: The aim of study is to evaluate the general performance and efficiency of the using real time intraoperative ultrasound system with Volume Navigation system technology in glioma. Compare glioma intraoperative ultrasound and contrast agent ultrasound images to obtained preoperative MRI with fusion image in a real-time., Patients and Methods: Fifteen patients had been performed fusion imaging involved intraoperative real-time ultrasound and contrast agent ultrasound with preoperative MR imaging including preoperative gadolinium-enhanced MRI from March 2017 to December 2017. The number of tumor was counted online fusion imaging in real time ultrasound with and without preoperative MR. We analyzed ultrasound coplanar MR modalities in real time including tumor location, margin (obscure or defined). In addition, intraoperative ultrasound enhancement pattern was analyzed compare it to preoperative reconstruction gadolinium-enhanced T1-weighted MRI. Two radiologists who made planning ultrasound assessment for the focus lesion based on a 4 scoring system according to the degree of confidence., Results: Thirteen of fifteen patients whose automatically registration successful intraoperative neurosurgery accepted preoperative MR examination. Seven of fifteen fine-tuning registration phase were performed and satisfactory with fusion image substantially. Intraoperatively, 73.3% (11/15) glioma nodules were definite on conventional B-mode US by a radiologist who doesn't know the MR result before fusion US with MRI. However, 100% tumors were detected on fusion B-mode ultrasound imaging with MRI. Two radiologists evaluated the score between fusion B-mode ultrasound and CEUS with coplanar MRI and had a result that score was upgraded in 69.2% (9/13) and 84.6% (11/13) patients. Inter-observer agreement was significant (kappa value = 1.0, p < 0.001) in B-mode ultrasound fusion image with MRI. Inter-observer agreement was moderate (kappa value = 0. 0.618, p < 0.001) in CEUS fusion image with MRI., Conclusion: Fusion imaging is very useful to detect poor sonographic visibility tumor on fusion B-mode US imaging with MR images. Fusion image may demonstrate multiplane images including same standard and nonstandard MRI and US images to help localize tumor. The additional real time fusion CEUS mode image with MR is a safe method for neurosurgery and the use of CEUS should be considered when fusion B-mode ultrasound imaging alone is not satisfactory for margin., (Copyright © 2018. Published by Elsevier B.V.)

Monitoring immune system activation of wild animals has garnered increasing interest within the field of ecological immunology, leading to an urgent need for non-invasive biomarkers measuring these changes. Urinary neopterin, a marker of the cell-mediated immune response, is validated as an immune-related biomarker in captive and laboratory animals. However, wild animals naturally host higher and chronic pathogen loads. Therefore, detection and quantification of additional infections via neopterin might not be possible against the background of a chronically challenged immune system. To assess the suitability of urinary neopterin in wild animals, we measured neopterin corrected for specific gravity with an enzyme immunoassay in 185 samples collected before, during and after a respiratory disease outbreak in 28 individuals from a group of wild chimpanzees (Taï National Park, Côte d'Ivoire). Urinary neopterin levels were significantly higher during periods when individuals showed respiratory symptoms versus before and after the outbreak. Furthermore, urinary neopterin levels were significantly higher in individuals that died, with higher levels already apparent before the outbreak, suggesting individuals may have an already activated immune system. Measuring urinary neopterin levels, with other biomarkers of energetic condition, stress challenges, and reproduction will contribute towards a deeper understanding of life-history trade-offs in wild animals.

Objective: To analyze the early effect of the cochlear implantation (CI) in children with cochlear incompletely partition type Ⅲ malformation (IP-Ⅲ). Method: Ten children with IP-Ⅲ malformation who underwent CI were recruited in this study. The hearing characteristics, preoperative speech performance and surgery were analyzed retrospectively. The aided hearing threshold with CI, the categories of auditory performance (CAP) score, speech intelligibility rating (SIR) score and speech perception were designed to access the benefits of CI. Ten children with normal cochlea were also enrolled as the control group. Demographic information of children in the control group including hearing loss and speech level before implantation, age at implantation, hearing aids using history, duration with CI were matched with those in the IP-Ⅲ group. The hearing threshold, CAP score and SIR score in the IP-Ⅲ group were compared with the control group using the SPSS 20.0 software. Result: The computed tomography of temporal bones showed typical IP-Ⅲ malformation in all patients. The electrode arrays were properly and totally implanted in all children. Cerebrospinal fluid gusher occurred intra-operatively, and no other complications in all patients. The pure tone average (PTA) threshold at the 3rd, 6th, 9th and 12th month after implantation were (40.8±8.5) dB HL, (36.1±9.1) dB HL, (32.5±6.8) dB HL and (33.0±7.3) dB HL, respectively. The PTA thresholds in the IP-Ⅲ group were similar to those in the control group at all tested time points ( P >0.05). At the 3rd, 6th, 9th and 12th month after implantation, the CAP scores in the IP-Ⅲ group were lower than those in the control group, but there was no significantly difference ( P >0.05). Furthermore, the SIR scores were lower than those in the control group, and there were significantly difference at the 6 th, 9 th and 12 th month after implantation ( P <0.05). Conclusion: CI was an effective treatment for children with IP-Ⅲ malformation. Surgery on IP-Ⅲ was challenging, however, seldom complication would occur with excellent surgical skills. Though the CI was benefit for IP-Ⅲ, the development of hearing and speech ability were slower than children with normal cochlea., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Pioglitazone (Piog) activates peroxisome proliferator activated receptor-γ (PPARγ) and is widely used in clinic for the treatment of diabetes mellitus. PPARγ in various tissues has the essential regulatory role of multiple metabolic function, suggest that PPARγ signaling may contribute to aging processes. However, little is known about the consequences of Piog on aging in aged animal models. We used apolipoprotein E deficient (apoE -/- ) mice model to evaluate the effects of Piog on aging-related disorders. Our results showed that long-term and low-dose Piog treatment significantly reduced aortic atherosclerosis, aging-related renal glomerulosclerosis and interstitial fibrosis, and hepatic steatosis, while improved the dermis in skin atrophy, compared to the control group. These morphological alterations were linked to the role of Piog, including regulation of plasma cholesterol and triglycerides (TG) levels, increased antioxidant superoxide dismutase (SOD) activity and decreased myeloperoxidase (MPO) activity. Moreover, accompanied with up-regulation of PPARγ expression, Piog had obviously increased the mRNA levels of anti-aging genes Sirtuin1 and Klotho, decreased the p53 protein level, and altered the expression of several genes involving cholesterol excretion, TG biosynthesis and inflammation in the liver. In conclusion, Piog treatment is effective to modulate the oxidative and inflammatory status, cell senescence, and lipid metabolism, contributing to attenuate several aging-related disorders in the aged apoE -/- mice, thereby maybe a promising protective therapy of aging and age-related diseases., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cross-sectional surveys of chimpanzee (Pan troglodytes) communities across sub-Saharan Africa show large geographical variation in malaria parasite (Plasmodium spp.) prevalence. The drivers leading to this apparent spatial heterogeneity may also be temporally dynamic but data on prevalence variation over time are missing for wild great apes. This study aims to fill this fundamental gap., Methods: Some 681 faecal samples were collected from 48 individuals of a group of habituated chimpanzees (Taï National Park, Côte d'Ivoire) across four non-consecutive sampling periods between 2005 and 2015., Results: Overall, 89 samples (13%) were PCR-positive for malaria parasite DNA. The proportion of positive samples ranged from 0 to 43% per month and 4 to 27% per sampling period. Generalized Linear Mixed Models detected significant seasonal and inter-annual variation, with seasonal increases during the wet seasons and apparently stochastic inter-annual variation. Younger individuals were also significantly more likely to test positive., Conclusions: These results highlight strong temporal fluctuations of malaria parasite detection rates in wild chimpanzees. They suggest that the identification of other drivers of malaria parasite prevalence will require longitudinal approaches and caution against purely cross-sectional studies, which may oversimplify the dynamics of this host-parasite system.

Prenatal ethanol exposure (PEE) induces hypothalamic-pituitary-adrenal (HPA) axis-related neuroendocrine metabolic programming alteration in the first generation (F1) rats. In this study, the HPA hormones and glucose/lipid phenotypes under basal state and stressed condition induced by a fortnight ice-water swimming were examined in F2 to verify the intergenerational effect. Under the basal state, serum corticosterone (CORT) and glucose of some PEE groups were lowered while those of serum triglycerides (TG) were increased comparing with controls. Following chronic stress, the percentage increase in CORT from the basal state tended to be greater for some PEE groups compared with controls while the percentage reduction of glucose and percentage elevation of TG were smaller. These results revealed that the low basal activity and hyper-responsiveness of the HPA axis as well as glucocorticoid-associated glucose and lipid phenotypic alterations were partially retained in F2, which indicates PEE-induced neuroendocrine metabolic programming alteration may have an intergenerational effect., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Epidemiological evidences show that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR). The IUGR offspring also present glucose intolerance and type 2 diabetes mellitus after maturity. We have previously demonstrated that PCE induced IUGR and increased susceptibility to adult metabolic syndrome in rats. This study aimed to further investigate the effects of PCE on glucose homeostasis in adult offspring rats. Pregnant rats were administered caffeine (120 mg/kg/day, intragastrically) from gestational days 11 to 20. PCE offspring presented partial catch-up growth pattern after birth, characterizing by the increased body weight gain rates. Meanwhile, PCE had no significant influences on the basal blood glucose and insulin phenotypes of adult offspring but increased the glucose tolerance, glucose-stimulated insulin section and β cell sensitivity to glucose in female progeny. The insulin sensitivity of both male and female PCE offspring were enhanced accompanied with reduced β cell fraction and mass. Western blotting results revealed that significant augmentation in protein expression of hepatic insulin signaling elements of PCE females, including insulin receptor (INSR), insulin receptor substrate 1 (IRS-1) and the phosphorylation of serine-threonine protein kinase (Akt), was also potentiated. In conclusion, we demonstrated that PCE reduced the pancreatic β mass but increased the glucose tolerance in adult offspring rats, especially for females. The adaptive compensatory enhancement of β cell responsiveness to glucose and elevated insulin sensitivity mainly mediated by upregulated hepatic insulin signaling might coordinately contribute to the increased glucose tolerance.

This study was conducted to investigate the role of different homocysteine metabolism-related vitamin (HMRV) levels in the correlation between hyperhomocysteinemia (HHCY) and ischemic stroke (IS) subtypes. Three hundred and forty-eight IS patients manifesting different vascular subtypes were subclassified on the basis of HMRV deficiencies. Correlation between HHCY and IS subtypes was investigated in all the subgroups. In this study, HHCY was significantly correlated with the IS subtypes in large artery atherosclerosis (OR 1.126, 95%CI: 1.051 ~ 1.206, P = 0.001) and small artery occlusion (OR 1.105, 95%CI: 1.023 ~ 1.193, P = 0.012). Subgroup analysis revealed a correlation between HHCY and IS subgroup (OR 1.201, 1.178, 95%CI: 1.081 ~ 1.334, 1.058 ~ 1.313, P = 0.001, P = 0.003, respectively) in HMRV deficiency, but not significantly with the IS subgroup in normal HMRV levels. Serum vitamin B12 concentrations are inversely correlated with both IS subtypes in HMRV deficiency subgroups (OR 0.992, 0.995, 95%CI: 0.987 ~ 0.996, 0.991 ~ 0.999, P < 0.001, P = 0.007, respectively), which may contribute to HHCY incidence in these populations. The correlation between HHCY and IS subtypes is affected by HMRV levels in this case-control study. Our findings are helpful to understand the inconsistency in prior homocysteine studies. Serum vitamin B12 levels may play a critical role in HHCY incidence in this Chinese population.Cerebrovascular disease has emerged as the leading cause of disability and mortality in both urban and rural areas of China (Neurology branch of Chinese Medical Association 2015). Ischemic stroke (IS) constitutes 60% to 80% of all cerebrovascular disease (Neurology branch of Chinese Medical Association 2014). Among a variety of risk factors, hyperhomocysteinemia (HHCY) has been closely correlated with IS due to intracranial small-vessel disease and extracranial large-artery disease (Selhub et al. 1995; Eikelboom et al. 2000; Alvarez et al. 2012; Jeon et al. 2014). However, the failure to lower homocysteine (HCY) via homocysteine metabolism-related vitamin (HMRV, including folic acid and vitamin B12 but not vitamin B6 in this study) supplementation to reduce stroke morbidity questions the role of HCY as a risk factor for stroke (Lonn et al. 2006; Hankey et al. 2010). Theoretically, HMRV supplementation merely lowers the incidence of stroke induced by HHCY resulting from HMRV deficiency, whereas HHCY-induced stroke concomitant with normal HMRV levels may be refractory to treatment. The correlation between HCY varying with HMRV levels and IS subtypes is still unclear. In this study, we investigated the impact of variation in HMRV levels on the correlation between HHCY and IS subtypes in 348 acute IS patients with large and small vessel diseases. We sought to determine the factors underlying the conflicting results associated with lowering HCY by HMRV supplementation to reduce stroke incidence.

The CO 2 flux from soil is an important component of global carbon cycle, and a small variation of soil CO 2 flux can prominently influence atmospheric CO 2 concentration and soil organic carbon stock. Soil erosion significantly influences soil CO 2 emission. However, the process of soil CO 2 flux during soil erosion and soil deposition remains uncertain. At the present study, a simulated experiment on soil erosion and deposition was conducted at Changwu State Key Agro-Ecological Station, Shaanxi, China. From July to September in 2014 and 2015, soil CO 2 flux was periodically measured using an automated CO 2 flux system LI-8100 (LI-COR, Lincoln, NE, USA) and soil temperature and moisture were collected by series data collection system of soil temperature and soil moisture (EM50, DECAGON, USA). The measurement frequency of soil CO 2 flux was once a week during 09:00 and 11:00. Soil temperature and soil moisture of 10 cm topsoil were measured continuously (at an interval of 30 minutes) during the experiment. At the same time, runoff and sediment were collected as well in each rain event, and then SOC content in sediment was measured. The results showed that soil CO 2 flux between erosion and deposition sites had a significant difference ( P <0.05), and soil CO 2 flux at deposition site [mean value 1.38 μmol·(m 2 ·s) -1 ] was 31% higher than that of soil CO 2 flux at deposition site [1.05 μmol·(m 2 ·s) -1 ], while temperature sensitivity at deposition site ( Q 10 :8.14) was 3 times as high as that at erosion site (2.34). Soil moisture at deposition site was 19% higher than that at erosion site ( P <0.05). Soil temperature was slightly higher at erosion site. The average SOC content (7.26 g·kg -1 ) increased by 6% in the sediment compared with the initial SOC content (6.83 g·kg -1 ). Soil moisture and SOC redistribution across erosion and deposition sites were influencing factors for soil CO 2 flux under erosional environment. In conclusion, soil CO 2 flux showed a significant variation at erosion site and deposition site. Changes in soil moisture and SOC contributed much to the difference in soil CO 2 flux across erosion and deposition sites.

A carotid body tumor (CBT) is a rare, non-chromaffin paraganglioma, and its diagnosis mainly depends on imaging modalities. The aim of this study was to investigate the ability of color Doppler ultrasound (CDU) in the diagnosis and assessment of CBT based on computed tomography (CT). We retrospectively reviewed the CDU and CT features of 49 consecutive CBTs and 23 schwannomas from 67 patients and compared these findings with surgical resection specimens. The mean size of CBT lesions on ultrasound scans and CT angiography (CTA) was 3.24 cm ± 0.82 cm (range, 1.6-5.2 cm) and 3.84 cm ± 1.08 cm (range, 1.8-6.8 cm), respectively, which had statistically significant difference (t = 9.815, p = 0.000). The vascularity of CBT lesions was richer than that of schwannoma lesions (p < 0.05). Intra-lesional vascularities feeding CBT mostly arose from the external carotid artery and had spectrum characteristics including low velocity and resistance. Peak systolic velocity (PSV) and resistance index (RI) of the vasa vasorum were 39.8 cm/s ± 19.8 cm/s and 0.54 ± 0.06, respectively. There was the correlation between CTA and CDU in identifying Shamblin type I CBT lesions, while CTA technique was superior for CDU, identifying Shamblin type II and III CBT lesions. Accuracy, specificity and sensitivity of CDU in diagnosing CBTs were 87.5% (63 of 72), 82.6% (19 of 23) and 89.8% (44 of 49), respectively. Both accuracy and sensitivity of CTA in diagnosing CBTs were 100%. CDU can be useful for assessment of Shamblin's type and intra-lesional blood flow of CBTs before its metastases, while CT imaging can reveal the relationship between lesions and adjacent arteries, as well as the involvement of the skull base. CDU combined with CT imaging can be used as an optimal detection modality for the assessment and management of CBT., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objective: To elucidate the transfected effect of albumin ultrasound microbubbles carrying peptide nucleic acids (PNAs) against c-myc gene to the vascular walls and their effect on the intimal proliferation induced by vascular denudation., Methods: A rabbit iliac artery intimal proliferation model was constructed and PNA against c-myc mRNA was designed and synthesized and was added to albumin solution before ultrasound microbubbles were prepared and encapsulated in matrix of albumin. The ultrasound microbubbles carrying PNA were transfected to intima under ultrasound exposure. The transfected effect was identified by a histochemical method and the expression of c-myc was detected by in situ hybridization. The proliferation of intimal smooth muscle cells was estimated by the expression of proliferative cell nuclear antigen (PCNA) of them. The intimal area and thickness were judged morphologically for intimal hyperplasia., Results: The ultrasound microbubbles with PNA were successfully prepared and c-myc PNA was transfected to vascular intimal cells. The expression of c-myc and PCNA by intimal vascular smooth muscle cells (vSMCs) was inhibited significantly and the intimal thickness and area were reduced remarkably., Conclusion: Transfection of c-myc PNA could inhibit proliferartion of vSMCs and intima in the rabbit iliac artery intimal proliferation model and the targeted transfection of albumin ultrasound microbubbles carrying PNA offers a feasible way to facilitate its access to specific cells in vivo and produce bioavailability.

Evaluating the response of soil microbial respiration to extreme precipitation event is significant for a better understanding about the influence of the change of precipitation regime on soil carbon cycling under global warming. A simulated experiment of extreme precipitations was conducted during the rainy season (July-September 2015) in the Changwu State Key Agro-Ecological Station, Shaanxi, China. The treatments consisted of three total precipitations in rainy season (600 mm, 300 mm, and 150 mm) and two precipitation regimes (10 mm, 150 mm; P 10 , P 150 ). Soil microbial respiration varied differently in the same single rainfall event among three precipitations. The variation coefficient of soil microbial respiration under 600 mm total precipitation was 36% (P 150 ) and 33% (P 10 ), and 28% and 22% under 300 mm total precipitation, 43% and 29% under 150 mm total precipitation. Under 600 mm total precipitation, the cumulative soil microbial respiration under P 150 was 20% less than that under P 10 ; however, the cumulative soil respiration of P 150 under 150 mm total precipitation was 22% more than that under P 10 ; and there was no significant difference between P 10 and P 150 under 300 mm total precipitation. Therefore, the duration in soil water stress must be considered to estimate soil microbial respirations under extreme precipitations.

This study aimed to detect the association of the MADD-FOLH1 single nucleotide polymorphisms (SNPs) and their haplotypes with the risk of coronary heart disease (CHD) and ischemic stroke (IS) in a Chinese Han population. Six SNPs of rs7395662, rs326214, rs326217, rs1051006, rs3736101, and rs7120118 were genotyped in 584 CHD and 555 IS patients, and 596 healthy controls. The genotypic and allelic frequencies of the rs7395662 SNP were different between controls and patients, and the genotypes of the rs7395662 SNP were associated with the risk of CHD and IS in different genetic models. Six main haplotypes among the rs1051006, rs326214, rs326217, rs3736101, and rs7120118 SNPs were detected in our study population, the haplotypes of G-G-T-G-C and G-A-T-G-T were associated with an increased risk of CHD and IS, respectively. The subjects with rs7395662GG genotype in controls had higher triglyceride (TG) and lower high-density lipoprotein cholesterol (HDL-C) levels than the subjects with AA/AG genotypes. Several SNPs interacted with alcohol consumption to influence serum TG (rs326214, rs326217, and rs7120118) and HDL-C (rs7395662) levels. The SNP of rs3736101 interacted with cigarette smoking to modify serum HDL-C levels. The SNP of rs1051006 interacted with body mass index ≥24 kg/m² to modulate serum low-density lipoprotein cholesterol levels. The interactions of several haplotypes and alcohol consumption on the risk of CHD and IS were also observed.

Background and Purpose: Nicotinic (ACh) receptor recovery from desensitization is modulated by PKC, but the PKC isozymes and the phosphorylation sites involved have not been identified. We investigated whether PKCε phosphorylation of α4β2 nAChRs regulates receptor recovery from desensitization., Experimental Approach: Receptor recovery from desensitization was investigated by electrophysiological characterization of human α4β2 nAChRs. Phosphorylation of the α4 nAChR subunit was assessed by immunoblotting of mouse synaptosomes. Hypothermia induced by sazetidine-A and nicotine was measured in Prkce(-/-) and wild-type mice., Key Results: Inhibiting PKCε impaired the magnitude of α4β2 nAChR recovery from desensitization. We identified five putative PKCε phosphorylation sites in the large intracellular loop of the α4 subunit, and mutating four sites to alanines also impaired recovery from desensitization. α4 nAChR subunit phosphorylation was reduced in synaptosomes from Prkce(-/-) mice. Sazetidine-A-induced hypothermia, which is mediated by α4β2 nAChR desensitization, was more severe and prolonged in Prkce(-/-) than in wild-type mice., Conclusions and Implications: PKCε phosphorylates the α4 nAChR subunit and regulates recovery from receptor desensitization. This study illustrates the importance of phosphorylation in regulating α4β2 receptor function, and suggests that reducing phosphorylation prolongs receptor desensitization and decreases the number of receptors available for activation., (© 2015 The British Pharmacological Society.)

Orchard and black locust are two typical plants for comprehensive control in the small watershed of land uses in Loess area. The analysis of soil carbon sequestration function changes of growing two plants is important to gain a deep understanding of soil carbon cycle process and its influencing factors of terrestrial ecosystems under the condition of small watershed comprehensive control. The experiment was conducted in the Changwu State Key Agro-Ecological Station, Shanxi, China. SOC, TN, fine root biomass and litter amount were determined at different age apple orchards and black locusts on the slope land of Wangdonggou watershed to study the variation characteristics of soil organic carbon and its influencing factors under two measurements. The results showed that: (1) SOC and TN contents in apple orchards significantly decreased with the increased age, whereas those in black locust showed an increased tendency with the age increased. Compared with the adjacent cropland,the SOC and TN contents in year 3, year 8, year 12 and year 18 apple orchards were decreased 3. 26%, 10. 54%, 18. 08%, 22. 55% and - 8. 08%, - 0. 48%, 4. 97%, 16. 91%, respectively. However,SOC and TN contents increased 5. 31%, 32. 36%, 44. 13% and 2. 49%, 15. 75%, 24. 22%, in year 12, year 18 and year 25 black locusts, respectively. (2) The fine root biomass in year 3, year 8, year 12, and year 18 apple orchards were about 25. 97% 66. 23%, 85. 71% and 96. 10% of the adjacent cropland, respectively; and the litter amounts were all 0 g . m-2. However, compared with adjacent cropland, The fine root biomass in year 12, year 18 and year 25 black locusts were increased 23. 53%, 79. 41%, 157. 35%, respectively; and the litter input rates were 194, 298 , 433 g . (m2 . a) -1, respectively. (3) The difference of organic matter input was the major factor which drove the variability of soil carbon sequestration function of apple orchard and black locust ecosystems.