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Hai-Lin Liu,1,* Rui-Hao Zhou,2,* Li-Li Luo,1 Xue Yuan,1 Ling Ye,2 He-Guo Luo1 1Department of Anesthesiology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, People’s Republic of China; 2Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: He-Guo LuoDepartment of Anesthesiology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, People’s Republic of ChinaEmail 542534631@qq.comBackground: Although ultrasound-guided transversus abdominis plane block (TAPB) is widely used in multimodal analgesia after cesarean delivery (CD), the complications of TAPB during analgesia after CD have rarely been reported.Methods: A total of 84 cases of CD were randomly assigned to either a ropivacaine group (R group) or ropivacaine + dexamethasone group (RD group) in this double-blind trial. The pain site and pain degree at rest and during activity at 2 h, 6 h, 10 h, 12 h, 14 h, 16 h, 20 h, and 24 h after maternal surgery were recorded. The consumption of opioids at 24h, postoperative nausea, vomiting, exhaustion, and other adverse reactions were recorded.Results: A total of 80 patients were included in the analysis of results. A total of 19 patients developed ISP, 14 in the R group and 5 in the RD group. The incidence of ISP in the R and RD groups was 35% and 12.5%, respectively. The results described above showed that combining dexamethasone with ropivacaine reduced the incidence of ISP, and the difference was statistically significant (P< 0.05). Two groups of women with positive ISP had higher values of opioid consumption than women with negative ISP, but the difference was not significant.Conclusion: Dexamethasone as an adjuvant for ropivacaine can effectively relieve the ISP of ultrasound-guided TAPB after CD, and can enhance the analgesic effect of ropivacaine.Keywords: dexamethasone, ropivacaine, cesarean delivery, transversus abdominis plane block, postoperative analgesia, injection site pain

Xi Lin,1 Cai Chang,2,3 Changjun Wu,4 Qin Chen,5 Yulan Peng,6 Baoming Luo,7 Lina Tang,8 Jing Li,9 Jihui Zheng,10 Ruhai Zhou,11 Guanghe Cui,12 Ao Li,13 Xuemei Wang,14 Linxue Qian,15 Jianxing Zhang,16 Chaoyang Wen,17 Joel Gay,18 Huili Zhang,18 Anhua Li,1 Yaling Chen2,3 1State Key Laboratory of Oncology in Southern China, Department of Ultrasound, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China; 2Department of Ultrasound, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China; 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P. R. China; 4Department of Ultrasound, First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China; 5Department of Ultrasound, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu 610072, P. R. China; 6Department of Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, P. R. China; 7Department of Ultrasound, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510235, P. R. China; 8Department of Ultrasound, Fujian Provincial Cancer Hospital, Fuzhou 350014, P. R. China; 9Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang 110004, P. R. China; 10Department of Ultrasound, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, P. R. China; 11Department of Ultrasound, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 315040, P. R. China; 12Department of Ultrasound, Binzhou Medical University Hospital, Binzhou 256603, P. R. China; 13Department of Ultrasound, Jiangsu Province Hospital, Nanjing 210029, P. R. China; 14Department of Ultrasound, The First Hospital of China Medical University, Shenyang 110001, P. R. China; 15Department of Ultrasound, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, P. R. China; 16Department of Ultrasound, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, P. R. China; 17Department of Ultrasound, First Affiliated Hospital of PLA General Hospital, Beijing 100037, P. R. China; 18Supersonic Imagine, Aix-en-Provence, France Purpose: This study aimed to investigate the value of shear wave elastography (SWE) for characterization of breast masses in a Chinese population. Patients and methods: Two thousand two hundred seventy-three women consented to be prospectively enrolled for the characterization of breast masses with ultrasound and SWE. Breast masses were known from symptoms, palpability, and/or previous imaging screening with mammography and/or ultrasound. Correlation of SWE qualitative and quantitative features with malignancy risk and impact on diagnostic performance of combining SWE features were assessed, and the Breast Imaging Reporting and Data System (BI-RADS) scoring was calculated using histopathology as reference. Results: Data of 2,262 masses (median size: 13 mm; range: 1.3–50) from 2,262 patients (median age: 43 years; range: 18–91) were investigated, of which 752 (33.3%) were malignant. Sensitivity and specificity of BI-RADS diagnosis were 97.5% (733/752) and 54.8% (827/1,510), respectively. By logistic regression, the combination of maximum elasticity (Emax) measurements with BI-RADS assessments increased the area under the receiver operating characteristic curve from 0.908 (95% CI: 0.896–0.920) to 0.954 (95% CI: 0.944–0.962). Using Emax of 30 kPa or lower to selectively downgrade BI-RADS 4a masses to follow-up, and Emax of 160 kPa or higher to selectively upgrade BI-RADS 3 lesions to biopsy, specificity significantly increased from 54.8% (827/1,510) to 66.1% (998/1,510) (P

Objective: To explore the correlation of the ratio of venous-arterial carbon dioxide (CO 2 ) tension difference to arterial-venous O 2 content difference (Pv-aCO 2 /Ca-vO 2 ) and venous-arterial CO 2 gradient (Pv-aCO 2 ) during cardiopulmonary bypass (CPB) with acute kidney injury (AKI) after pediatric cardiac surgery. Methods: The clinical data of children (1 month ≤ age ≤ 3 years old) who underwent open heart surgery under CPB in West China Hospital of Sichuan University from March 2021 to August 2022 were retrospectively analyzed. All paired blood gases of the children during CPB (the sampling time interval of arterial and venous blood was within 10 minutes) were collected. According to the Failure, Loss, End-Stage Renal Disease (pRIFLE) diagnostic criteria, the children were divided into AKI group and non-AKI group. Multivariate logistic regression analysis was performed to identify the risk factors of postoperative AKI in pediatric cardiac surgery. Results: A total of 213 children were enrolled (101 males and 112 females), aged 12(6, 24) months, and 84 of them (39.4%) developed AKI. Three children died in AKI group, with a mortality of 3.6%. There were no deaths in non-AKI group. The incidence of postoperative low cardiac output syndrome (LCOS) was higher in AKI group [29.8% (25/84) vs 7.0% (9/129), P <0.001]. In addition, compared with the non-AKI group, children in AKI group had longer recovery time [15 (6, 78) h vs 6 (3, 19) h, P <0.001], mechanical ventilation time [17 (7, 97) h vs 6 (4, 20) h, P <0.001], intensive care unit (ICU) stay [6 (4, 11) d vs 3 (2, 5) d, P <0.001], and hospital stay [12 (9, 18) d vs 9 (8, 11) d, P <0.001]. A total of 317 arterial and venous blood gas pairs from 30 ( n =207), 60 ( n =75) and 90 min ( n =35) after aortic clamping were included in the analysis. Univariate analysis showed that Pv-aCO 2 /Ca-vO 2 ( P =0.015) at 30 min after aortic clamping, Pv-aCO 2 ( P =0.041) and Pv-aCO 2 /Ca-vO 2 ( P =0.014) at 60 min after aortic clamping, peak Pv-aCO 2 ( P =0.009), peak Pv-aCO 2 /Ca-vO 2 ( P <0.001) and the average value of Pv-aCO 2 /Ca-vO 2 ( P =0.001) were higher in AKI group. Multivariate logistic regression analysis showed that longer duration of CPB ( OR =1.013, 95% CI : 1.003-1.023, P =0.012), higher peak Pv-aCO 2 /Ca-vO 2 ( OR =1.337, 95% CI : 1.037-1.723, P =0.025) were risk factors for AKI. Conclusion: The occurrence of AKI after pediatric cardiac surgery is related to the short-term adverse clinical prognosis, and longer duration of CPB and higher peak Pv-aCO 2/ Ca-vO 2 are independent risk factors for AKI.

By reason of surgical demand, the majority of cardiovascular procedures still depend on the use of cardiopulmonary bypass (CPB). Due to the nonphysiological state of CPB, it can cause complex and unpredictable inflammatory response, which may lead to significant morbidity and mortality. Unfortunately, the pharmacological and mechanical strategies that currently exist do not offer significant advantages in controlling inflammatory response and improving patient outcomes. The best strategy to reduce inflammation in CPB is still uncertain. In recent years, adsorptive blood purification techniques (BPTs) have emerged, among which CytoSorb is the latest representative device. Currently, the primary application area of adsorptive BPTs is in the control and treatment of systemic hyperinflammatory states, such as refractory septic shock patients. However, the evidences on efficacy and safety of adsorptive BPTs application during CPB surgery are still inconclusive, so we summarize the relevant evidences here and suggest future potential research areas., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Meng-Han Liu et al.)

Background: Cardiac surgery-associated acute kidney injury (CS-AKI) is common in infants and is associated with negative outcomes. Nadir indexed oxygen delivery (DO 2 i) during cardiopulmonary bypass (CPB) is associated with the occurrence of postoperative CS-AKI, with critical thresholds for DO 2 i reported to be 262 to 300 mL/min/m 2 in adults. However, given that infants have a higher metabolic rate and oxygen demand, the critical DO 2 i in infants is not comparable with existing adult standards. This study aimed to explore the critical DO 2 i threshold during pediatric CPB., Methods: Between March 2019 and April 2020, 106 consecutive infants undergoing cardiac surgery with CPB were admitted to this prospective observational cohort study. The DO 2 i levels of each patient were monitored during CPB. Pre- and intraoperative factors were tested for independent association with CS-AKI. The postoperative outcomes of patients with or without CS-AKI were compared., Results: In our patient population (n = 83), we identified 25 patients (38.5%) with postoperative CS-AKI. Multivariate analysis revealed 2 independent risk factors for onset of CS-AKI: CPB duration and nadir DO 2 i. The lowest suitable DO 2 i during CPB in the present population was 353 mL/min/m 2 (sensitivity, 65.6%; specificity, 74.5%). CS-AKI during pediatric CPB remained significantly associated with an increased morbidity, related mainly to a postoperative low cardiac output syndrome, but not to mortality., Conclusions: The lowest suitable DO 2 i during CPB in the infant population undergoing cardiac surgery was 353 mL/min/m 2 . Below this threshold, there was a high probability of inducing CS-AKI., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Nano hydroxyapatite (nHAp), a main component of the inorganic composition of human bones and teeth, is widely used in bone tissue engineering, bone defect repair and replacement, for example, for its biocompatibility, bioactivity, bioaffinity and the ability to induce bone regeneration. Nano hydroxyapatite contains calcium and phosphorus, elements that can be replaced through the normal metabolic channels of the human body. Therefore, after implantation, it can be partially or completely absorbed and replaced by human tissues and can effectively assist bone regeneration, which makes it an ideal material for bone repair. However, traditional nHAp material is brittle and hard to be degraded in human body. In addition, nHAp has poor stability due to its high surface energy and tendency for agglomeration, which causes rapid attenuation of its mechanical strength and limits its clinical application. At present, the mechanical properties and biocompatibility of nHAp can be effectively improved by loading the related growth factors, proteins, peptides and other bioactive molecules, so as to better meet the biological requirements of bone repair materials. However, the traditional physicochemical modification methods are complicated and may interfere with the bioactivity of nHAp. It is simple to biomimetically synthesize nanomaterials by direct utilization of the molecular recognition and self-assemble capabilities of biomolecules or living microorganisms. Furthermore, the properties of the synthesized nanomaterials are stable, and the method has been extensively studied in recent years. Due to the unique crystaline structure and physicochemical properties of nHAp, results of a large number of studies have shown that its affinity with biological molecules can be used to produce bioactive nHAp by biomimetic synthesis methods. Biomimetically synthesized nHAp is expected to become the mainstream bone tissue engineering scaffold material. Analyzing and summarizing the biomimetic synthetic process and the characteristics of different nHAp materials will facilitate further development of bone defect repair materials with better mechanical and biological properties. Herein we reviewed methods of biomimetic synthesis of nHAp based on different biomolecular templates. Furthermore, we also discussed applications of biomimetic synthesized nHAp in bone tissue engineering, which can used as reference information for further research and development of new-generation bone repair biomaterials., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Chronically SHIV SF162P3N -infected cynomolgus monkeys were used to determine the effects of the antibody-mediated acute CD4 + T cell depletion on viral load as well as on the immunological factors associated with disease progression. Compared with the control animals, CD4 + T cell-depleted animals with SHIV infection showed (i) little alteration in plasma viral load over the period of 22 weeks after the depletion; (ii) increased CD4 + T cell proliferation and turnover of macrophages at the early phase of the depletion, but subsequent decline to the basal levels; and (iii) little impact on the expression of the inflammatory cytokines and CC chemokines associated with disease progression. These findings indicate that the antibody-mediated acute CD4 + T cell depletion had minimal impact on plasma viral load and disease progression in chronically SHIV SF162P3N -infected cynomolgus monkeys. Future investigations are necessary to identify the key factor(s) related to the immune activation and macrophage infection during the CD4 deletion in chronic viral infection., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Fasting and caloric restriction have a potential means of anti-inflammatory, as they can decrease the level of systemic inflammation. Although encouraging results have been obtained in animal experiments, there is no consensus on whether these results are applicable to human. The objective of this systematic review and meta-analysis is to analyze the influence of fasting and caloric restriction on inflammation levels in humans., Methods: The systematic review and meta-analysis will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The following eight databases will be searched:(The retrieval time is from the establishment of each database to December 2020): PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge infrastructure (CNKI), China Biology Medicine (CBM), Wan Fang Data, the Chinese Science and Technology Periodical Database (VIP). Relevant data will be performed by Revman 5.3 software provided (Cochrane Collaboration) and Stata 14.0 statistical software., Results: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal., Conclusions: This systematic review will provide evidence to judge the effectiveness of fasting and calorie restriction in human subjects, so as to provide a sound basis for future research and lifestyle promotion., Inplasy Registration Number: INPLASY202130026., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Intralipid is a necessary fatty acid carrier that has been safely used as an energy supplier in the clinic. It has played an important role in rescuing the cardiac arrest caused by local anesthetic toxicity. In recent years, experimental studies have shown that intralipid postconditioning (ILPC) could reduce myocardial ischemic/reperfusion (I/R) injuries. Our research group has innovatively conducted a pilot randomized controlled trial (RCT), and the results showed that ILPC could reduce the release of cTnT and CK-MB, biomarkers of myocardial I/R injury, in valve replacement surgery. However, the potential effects of ILPC on the clinical outcome of adult cardiac surgery patients are unclear. Intralipid postconditioning in patients of cardiac surgery undergoing cardiopulmonary bypass (iCPB) trial is aimed to further study whether ILPC could improve short-term and long-term clinical outcome, as well as cardiac function in adult cardiac surgery patients., Methods: The iCPB trial is an ongoing, single-center, prospective, double-blinded, large sample RCT. In total, 1000 adults undergoing cardiac surgery will be randomly allocated to either the ILPC group or the control group. The intervention group received an intravenous infusion of 2 mL/kg of 20% intralipid (medium-chain and long-chain fat emulsion injection C6~C24, Pharmaceutical) within 10 min before aortic cross-unclamping, and the control group received an equivalent volume of normal saline. The primary endpoints are complex morbidity of major complications during hospitalization and all-cause mortality within 30 days after surgery. The secondary endpoints include (1) all-cause mortality 6 months and 1 year postoperatively; (2) the quality of life within 1 year after surgery, using the QoR-15 questionnaire; (3) the postoperative cardiac function evaluated by LVEF, LVEDS, and LVEDD, and the myocardial injury evaluated by CK-MB, cTnT, and BNP; and (4) short-term clinical outcomes during hospitalization and total cost are also detailed evaluated., Discussion: The iCPB trial is the first to explore ILPC on the clinical outcome of adult cardiac surgery patients. The results are expected to provide potential evidences about whether ILPC could reduce the morbidity and mortality and improve the cardiac function and quality of life. Therefore, the results will provide a rationale for the evaluation of the potentially clinically relevant benefit of intralipid therapy., Trial Registration: Chictr.org.cn ChiCTR1900024387. Prospectively registered on 9 July 2019.

Aim: This study aimed to explore the genetic and epigenetic similarities between chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma (LUAD). Materials & methods: We mainly used Weighted correlation network analysis, protein-protein interaction network and pivot analysis to identify hub modules, bridge regulators, bridge genes and hub-driving genes in both diseases and carried out verifying using external datasets. Results: We identified eight bridge regulators, 19 key molecules in the COPD model and ten key molecules in the LUAD model. Moreover, we validated that CDC5L could be a reliable biomarker in COPD and may regulate cell proliferation and metastasis in LUAD via promoter methylation. Conclusion: Our results might form a theoretical foundation for future study at an epigenetic level.

Background: The number of asymptomatic infected patients with coronavirus disease 2019 (COVID-2019) is rampaging around the world but limited information aimed on risk factors of asymptomatic infections. The purpose of this study is to investigate the risk factors of symptoms onset and clinical features in asymptomatic COVID-19 infected patients. Methods: A retrospective study was performed in 70 asymptomatic COVID-2019 infected patients confirmed by nucleic acid tests in Hunan province, China between 28 January 2020 and 18 February, 2020. The epidemiological, clinical features and laboratory data were reviewed and analyzed. Presence or absence at the onset of symptoms was taken as the outcome. A Cox regression model was performed to evaluate the potential predictors of the onset of symptoms. Results: The study included 36 males and 34 females with a mean age of 33.24±20.40 years (range, 0.5-84 years). There were 22 asymptomatic carriers developed symptoms during hospitalization isolated observation, and diagnosed as confirmed cases, while 48 cases remained asymptomatic throughout the course of disease. Of 70 asymptomatic patients, 14 (14/70, 20%) had underlying diseases, 3 (3/70, 4.3%) had drinking history, and 11 (11/70, 15.7%) had smoking history. 22 patients developed symptoms onset of fever (4/22, 18.2%), cough (13/22, 59.1%), chest discomfort (2/22, 9.1%), fatigue (1/22, 4.5%), pharyngalgia (1/22, 4.5%) during hospitalization; only one (1/22, 4.5%) patient developed signs of both cough and pharyngalgia. Abnormalities on chest CT were detected among 35 of the 69 patients (50.7%) after admission, except for one pregnant woman had not been examined. 4 (4/70, 5.7%) and 8 (8/70, 11.4%) cases showed leucopenia and lymphopenia. With the effective antiviral treatment, all the 70 asymptomatic infections had been discharged, none cases developed severe pneumonia, admission to intensive care unit, or died. The mean time from nucleic acid positive to negative was 13.2±6.84 days. Cox regression analysis showed that smoking history (P=0.028, hazard ratio=4.49, 95% CI 1.18-17.08) and existence of pulmonary disease (P=0.038, hazard ratio=7.09, 95% CI 1.12-44.90) were risk factors of the onset of symptoms in asymptomatic carries. Conclusion: The initially asymptomatic patients can develop mild symptoms and have a good prognosis. History of smoking and pulmonary disease was prone to illness onset in asymptomatic patients, and it is necessary to be highly vigilant to those patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Monocytic-lineage cells in the central nervous system (CNS), including microglia and brain resident macrophages, are the key players in the CNS innate immunity against viral infections, including human immunodeficiency virus (HIV). However, these cells also serve as the major targets and reservoirs for HIV in the CNS. To address the question of how HIV can establish persistent infection in the target cells in the CNS, we examined whether HIV has the ability to counteract Toll-like receptor 3 (TLR3) activation-mediated antiviral immunity in microglia and macrophages. We observed that HIV latently infected microglial cells (HC69·5) expressed reduced levels of TLR3 and TLR3 activation-mediated interferons (IFN-α/β and IFN-λ) as compared with the uninfected control cells (C20). In addition, HIV infection of primary human macrophages suppressed the expression of TLR3 and the IFNs. HIV infection also inhibited the expression of the antiviral IFN-stimulated genes (ISGs) and the HIV-restriction miRNAs. Mechanistically, HIV infection inhibited the phosphorylation of IFN regulatory factors (IRF3 and IRF7) and signal transducer and activator of transcription proteins (STAT1 and STAT3) in both HIV latently infected microglia and acutely infected macrophages. These findings provide previously unrecognized and sound mechanisms for HIV infection and persistence in the primary target and reservoir cells in the brain., (© 2020 John Wiley & Sons Ltd.)

Background: Focal nodular hyperplasia (FNH) has very low potential risk, and a tendency to spontaneously resolve. Hepatocellular adenoma (HCA) has a certain malignant tendency, and its prognosis is significantly different from FNH. Accurate identification of HCA and FNH is critical for clinical treatment., Aim: To analyze the value of multi-parameter ultrasound index based on logistic regression for the differential diagnosis of HCA and FNH., Methods: Thirty-one patients with HCA were included in the HCA group. Fifty patients with FNH were included in the FNH group. The clinical data were collected and recorded in the two groups. Conventional ultrasound, shear wave elastography, and contrast-enhanced ultrasound were performed, and the lesion location, lesion echo, Young's modulus (YM) value, YM ratio, and changes of time intense curve (TIC) were recorded. Multivariate logistic regression analysis was used to screen the indicators that can be used for the differential diagnosis of HCA and FNH. A ROC curve was established for the potential indicators to analyze the accuracy of the differential diagnosis of HCA and FNH. The value of the combined indicators for distinguishing HCA and FNH were explored., Results: Multivariate logistic regression analysis showed that lesion echo ( P = 0.000), YM value ( P = 0.000) and TIC decreasing slope ( P = 0.000) were the potential indicators identifying HCA and FNH. In the ROC curve analysis, the accuracy of the YM value distinguishing HCA and FNH was the highest (AUC = 0.891), which was significantly higher than the AUC of the lesion echo and the TIC decreasing slope ( P < 0.05). The accuracy of the combined diagnosis was the highest (AUC = 0.938), which was significantly higher than the AUC of the indicators diagnosing HCA individually ( P < 0.05). This sensitivity was 91.23%, and the specificity was 83.33%., Conclusion: The combination of lesion echo, YM value and TIC decreasing slope can accurately differentiate between HCA and FNH., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Rationale: Patients of critical pulmonary artery stenosis would face severe hypoxemia, cardiac failure as well as massive hemorrhage during percutaneous balloon dilation and pulmonary arterial stent implantation. Here, we present a case in which the elective use of extracorporeal membrane oxygenation (ECMO) support successfully facilitated safe percutaneous balloon dilation of pulmonary artery and stent implantation on a patient with severe pulmonary artery stenosis caused by aorto-arteritis., Patient Concerns: A 47-year-old man was hospitalized due to 10 years of post-exercise exhaustion and shortness of breath. Half a month ago the symptoms deteriorated. He also manifested systemic edema and could only sit upright to breath during night time. Computed tomographic angiography (CTA) indicated severe pulmonary stenosis caused by aorto-arteritis., Diagnoses: Right pulmonary artery stenosis, left pulmonary artery occlusion, severe tricuspid regurgitation, right atrium, and ventricle enlargement, atrial fibrillation with rapid ventricular rates, NYHA class IV, pulmonary infection., Interventions: V-A ECMO support was considered during percutaneous balloon dilation of pulmonary artery and stent implantation., Outcomes: The patient remained hemodynamically stable throughout the procedure with no inotropic support. ECMO was successfully weaned off after the intervention, with no procedural complications. Postoperative echocardiography indicated much better heart function, and he was discharged uneventfully 5 days later., Conclusion: V-A ECMO is capable of preventing hypoxemia and providing effective circulation support during cardiac intervention in patients of severe pulmonary stenosis.

The female reproductive tract is a major site of HIV sexual transmission. We here examined whether human cervical epithelial cells (HCEs) can be immunologically activated and produce antiviral factors against HIV. We demonstrated that HCEs (End1/E6E7 cells) possess the functional toll-like receptor (TLR)3 signaling system, which could be activated by Poly I:C and induce multiple cellular HIV restriction factors. The treatment of primary human macrophages with supernatant (SN) from TLR3-activated End1/E6E7 cell cultures resulted in HIV inhibition. This SN-mediated HIV inhibition was mainly through the induction of interferons (IFN)-β and IFN-λs, as the antibodies to IFN-β or IFN-λs receptor could effectively block the SN-mediated anti-HIV effect. Further studies showed that the incubation of macrophages with SN from the activated cervical epithelial cell cultures induced the expression of a number of IFN-stimulated genes (ISGs), including IFN-stimulated gene (ISG15), ISG56, 2', 5'-oligoadenylate synthetase 1 (OAS 1), OAS 2, Myxovirus Resistance A (MxA), MxB, and Guanylate-binding protein 5 (GBP5). In addition, TLR3-activated cells produced the CC chemokines [regulated on activation, normal T cell expressed and secreted (RANTES), Human macrophage inflammatory protein 1 alpha (MIP-1α), MIP-1β] the ligands of HIV entry co-receptor CCR5. These observations support further studies on HCEs as potentially crucial and alternative targets for immunological intervention to control and prevent HIV sexual transmission., (© 2018 S. Karger AG, Basel.)

Epigallocatechin-3-gallate (EGCG), a natural and major ingredient of green tea, has been shown to have anti-inflammation and anti-HIV-1 properties. We demonstrated that the intrarectal administration of EGCG could protect rhesus macaques from repetitive, intrarectal challenges with low-dose SHIV SF162P3N . This protection has a per-exposure risk reduction of 91.5% (P = 0.0009; log-rank test) and a complete protection of 87.5% (P < 0.001; Fisher's exact test). All protected animals showed no evidence of systemic and mucosal SHIV infection as demonstrated by the absence of viral RNA, DNA and antibodies. In contrast, all controls became infected after repeated SHIV challenges (a median of 2.5 times, range of 1-8 times). Mechanistically, EGCG could block the binding of HIV-1 gp120 to CD4 receptor and suppress the macrophage infiltration/activation in the rectal mucosa of macaques. These data support further clinical evaluation and development of EGCG as a novel, safe and cost-effective microbicide for preventing sexual transmission of HIV-1.

As a rich source of CD4 + T cells and macrophages, the gastrointestinal (GI) tract is a major target site for HIV infection. The interplay between GI-resident macrophages and intestinal epithelial cells (IECs) constitutes an important element of GI innate immunity against pathogens. In this study, we investigated whether human IECs have the ability to produce antiviral factors that can inhibit HIV infection of macrophages. We demonstrated that IECs possess functional toll-like receptor 3 (TLR3), the activation of which resulted in induction of key interferon (IFN) regulatory factors (IRF3 and IRF7), IFN-β, IFN-λ, and CC chemokines (MIP-1α, MIP-1β, RANTES), the ligands of HIV entry co-receptor CCR5. In addition, TLR3-activated IECs release exosomes that contained the anti-HIV factors, including IFN-stimulated genes (ISGs: ISG15, ISG56, MxB, OAS-1, GBP5, and Viperin) and HIV restriction miRNAs (miRNA-17, miRNA-20, miRNA-28, miRNA-29 family members, and miRNA-125b). Importantly, treatment of macrophages with supernatant (SN) from the activated IEC cultures inhibited HIV replication. Further studies showed that IEC SN could also induce the expression of antiviral ISGs and cellular HIV restriction factors (Tetherin and APOBEC3G/3F) in HIV-infected macrophages. These findings indicated that IECs might act as an important element in GI innate immunity against HIV infection/replication.

Bowman-Birk inhibitor (BBI) is a soybean-derived protease inhibitor that has anti-inflammation and anti-HIV effect. Here, we further investigated the anti-HIV action of BBI in macrophages, focusing on its effect on viral entry. We found that BBI could significantly block HIV entry into macrophages. Investigation of the mechanism(s) of the BBI action on HIV inhibition showed that BBI down-regulated the expression of CD4 receptor (as much as 80%) and induced the production of the CC chemokines (up to 60 folds at protein level) in macrophages. This inhibitory effect of BBI on HIV entry could be blocked by the neutralization antibodies to CC chemokines. These findings indicate that BBI may have therapeutic potential as a viral entry inhibitor for the prevention and treatment of HIV infection., (Copyright © 2017. Published by Elsevier Inc.)

Background: This study aimed to evaluate the effect of intralipid postconditioning (ILPC) on myocardial damage in patients undergoing valve replacement surgery with concomitant radiofrequency ablation (RFA) for atrial fibrillation (AF)., Methods: Randomized patient and assessor-blind controlled trial conducted in adult patients undergoing valve replacement surgery with concomitant RFA. Sixty-nine patients were randomly assigned to ILPC group (n = 34) or control group (n = 35): ILPC group received an intravenous infusion of 20% intralipid (2 mL/kg) just 10 minutes before aortic cross-unclamping, and control group received an equivalent volume of normal saline. Serum cardiac troponin-T (cTnT) and creatine kinase-MB (CK-MB) was measured before surgery and at 4, 12, 24, 48, and 72 hours after surgery. The primary endpoints were the 72-hour area under the curve (AUC) for cTnT and CK-MB., Results: The total 72-hour AUC of cTnT (P = .33) and CK-MB (P = .52) were comparable between 2 groups. The left ventricle ejection fraction at discharge (P = .011) was higher in the ILPC group than that in the control group, while the AF recurrence did not differ significantly between 2 groups., Conclusions: There was no observed beneficial effect of ILPC on myocardial injury documented by the cardiac biomarkers in patients undergoing valve replacement surgery with concomitant RFA, and the effect of intralipid against myocardial I/R injury is undetectable within the background of massive biomarker release following ablation owing to localized myocardial necrosis. Besides, there are no other published data about the cardioprotective role of intralipid in patients undergoing this procedure and benefits of this protection need further studies to validate., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

To help reveal the diversity and evolution of bat coronaviruses we collected 1067 bats from 21 species in China. A total of 73 coronaviruses (32 alphacoronaviruses and 41 betacoronaviruses) were identified in these bats, with an overall prevalence of 6.84%. All newly-identified betacoronaviruses were SARS-related Rhinolophus bat coronaviruses (SARSr-Rh-BatCoV). Importantly, with the exception of the S gene, the genome sequences of the SARSr-Rh-BatCoVs sampled in Guizhou province were closely related to SARS-related human coronavirus. Additionally, the newly-identified alphacoronaviruses exhibited high genetic diversity and some may represent novel species. Our phylogenetic analyses also provided insights into the transmission of these viruses among bat species, revealing a general clustering by geographic location rather than by bat species. Inter-species transmission among bats from the same genus was also commonplace in both the alphacoronaviruses and betacoronaviruses. Overall, these data suggest that high contact rates among specific bat species enable the acquisition and spread of coronaviruses., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Human semen contains a factor that can enhance HIV infection up to 10-fold in cultures. This factor is termed semen-derived enhancer of virus infection (SEVI) and is composed of proteolytic fragments (PAP248-286) from prostatic acid phosphatase in semen. In this study, we examined whether macaque SEVI can facilitate simian immunodeficiency virus (SIV) or chimeric simian/human immunodeficiency virus (SHIV) infection. We also studied the effect of epigallocatechin gallate (EGCG) on macaque SEVI-mediated SIV or SHIV enhancement., Methods: SIV or SHIV was mixed with different concentrations of macaque SEVI in the presence or absence of EGCG. The mixture was added to cultures of TZM-bl cells or macaque PBMCs. The effect of EGCG on macaque SEVI was measured by Congo-red staining assay and thioflavin T (ThT) fluorescence assay and was visualized by a transmission electron microscope., Results: We identified that there is one amino acid difference at the site of 277 between human PAP248-286 and macaque PAP248-286. Macaque SEVI significantly enhanced SIV or SHIV infection of TZM-bl cells and macaque PBMCs. EGCG could block macaque SEVI-mediated enhancement of SIV or SHIV infection. Mechanistically, EGCG could degrade the formation of macaque SEVI amyloid fibrils that facilitates HIV attachment to the target cells., Conclusions: The finding that macaque SEVI could enhance SIV or SHIV infection indicates the possibility to use the macaque SEVI in vivo studies with the macaque models. In addition, future studies are necessary to examine whether EGCG can be used as an effective microbicide for preventing SIV or SHIV mucosal transmission.

Type III interferons (IFN-λs) have been demonstrated to inhibit a number of viruses, including HIV. Here, we further examined the anti-HIV effect of IFN-λs in macrophages. We found that IFN-λs synergistically enhanced anti-HIV activity of antiretrovirals [azidothymidine (AZT), efavirenz, indinavir, and enfuvirtide] in infected macrophages. Importantly, IFN-λs could suppress HIV infection of macrophages with the drug-resistant strains, including AZT-resistant virus (A012) and reverse transcriptase inhibitor-resistant virus (TC49). Mechanistically, IFN-λs were able to induce the expression of several important anti-HIV cellular factors, including myxovirus resistance 2 (Mx2), a newly identified HIV post-entry inhibitor and tetherin, a restriction factor that blocks HIV release from infected cells. These observations provide additional evidence to support the potential use of IFN-λs as therapeutics agents for the treatment of HIV infection.

The Bowman-Birk inhibitor (BBI), a soybean-derived protease inhibitor, is known to have anti-inflammatory effect in both in vitro and in vivo systems. Macrophages play a key role in inflammation and immune activation, which is implicated in HIV disease progression. Here, we investigated the effect of BBI on HIV infection of peripheral blood monocyte-derived macrophages. We demonstrated that BBI could potently inhibit HIV replication in macrophages without cytotoxicity. Investigation of the mechanism(s) of BBI action on HIV showed that BBI induced the expression of IFN-β and multiple IFN stimulated genes (ISGs), including Myxovirus resistance protein 2 (Mx2), 2',5'-oligoadenylate synthetase (OAS-1), Virus inhibitory protein (viperin), ISG15 and ISG56. BBI treatment of macrophages also increased the expression of several known HIV restriction factors, including APOBEC3F, APOBEC3G and tetherin. Furthermore, BBI enhanced the phosphorylation of IRF3, a key regulator of IFN-β. The inhibition of IFN-β pathway by the neutralization antibody to type I IFN receptor (Anti-IFNAR) abolished BBI-mediated induction of the anti-HIV factors and inhibition of HIV in macrophages. These findings that BBI could activate IFN-β-mediated signaling pathway, initialize the intracellular innate immunity in macrophages and potently inhibit HIV at multiple steps of viral replication cycle indicate the necessity to further investigate BBI as an alternative and cost-effective anti-HIV natural product.

Although rodents are important reservoirs for RNA viruses, to date only one species of rodent coronavirus (CoV) has been identified. Herein, we describe a new CoV, denoted Lucheng Rn rat coronavirus (LRNV), and novel variants of two Betacoronavirus species termed Longquan Aa mouse coronavirus (LAMV) and Longquan Rl rat coronavirus (LRLV), that were identified in a survey of 1465 rodents sampled in China during 2011-2013. Phylogenetic analysis revealed that LAMV and LRLV fell into lineage A of the genus Betacoronavirus, which included CoVs discovered in humans and domestic and wild animals. In contrast, LRNV harbored by Rattus norvegicus formed a distinct lineage within the genus Alphacoronavirus in the 3CL(pro), RdRp, and Hel gene trees, but formed a more divergent lineage in the N and S gene trees, indicative of a recombinant origin. Additional recombination events were identified in LRLV. Together, these data suggest that rodents may carry additional unrecognized CoVs., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Bacillus amyloliquefaciens HB-26, a Gram-positive bacterium was isolated from soil in China. SDS-PAGE analysis showed this strain secreted six major protein bands of 65, 60, 55, 34, 25 and 20 kDa. A bioassay of this strain reveals that it shows specific activity against P. brassicae and nematode. Here we describe the features of this organism, together with the draft genome sequence and annotation. The 3,989,358 bp long genome (39 contigs) contains 4,001 protein-coding genes and 80 RNA genes.

It is known that the medial vestibular nucleus (MVN) and the cerebellar flocculus are the key areas, which contribute to the behavioral recovery ("vestibular compensation") after unilateral labyrinthectomy (UL). In these areas, how the genetic activities of the metabotropic glutamate receptors mGluR2 and mGluR7 performance after UL is unknown. With the means of quantitative real-time PCR, Western blotting, and immunohistochemistry, we analyzed the expression of mGluR2 and mGluR7 in the bilateral MVN and the flocculus of rats in different stages after UL (the 1st, 3rd, and 7th day). Our results show that in the MVN, the mRNA, and protein expressions of mGluR7 were ipsilaterally decreased at the 1st day following UL. However, in the MVN, no change was observed in the mRNA and protein expressions of mGluR2. On the other hand, the mRNA and protein expression of mGluR2 were enhanced in the ipsilateral flocculus at the 1st day following UL, while in the flocculus no change was shown in mGluR7 mRNA and protein expressions. Our results suggest that mGluR2 and mGluR7 may contribute to the early rebalancing of spontaneous resting activity in the MVN.

Background: Longquan City, Zhejiang province, China, has been seriously affected by hemorrhagic fever with renal syndrome (HFRS) since the first cases were registered in 1974. To understand the epidemiology and emergence of HFRS in Longquan, which may be indicative of large parts of rural China, we studied long-term incidence patterns and performed a molecular epidemiological investigation of the causative hantaviruses in human and rodent populations., Method/principal Findings: During 1974-2011, 1866 cases of HFRS were recorded in Longquan, including 20 deaths. In 2011, the incidence of HFRS remained high, with 19.61 cases/100,000 population, despite the onset of vaccination in 1997. During 1974-1998, HFRS cases in Longquan occurred mainly in winter, while in the past decade the peak of HFRS has shifted to the spring. Notably, the concurrent prevalence of rodent-borne hantaviruses in the region was also high. Phylogenetic analyses of viral sequences recovered from rodents in Longquan revealed the presence of novel genetic variants of Gou virus (GOUV) in Rattus sp. rats and Hantaan virus (HTNV) in the stripe field mice, respectively. Strikingly, viral sequences sampled from infected humans were very closely related to those from rodents., Conclusions/significance: HFRS represents an important public health problem in Longquan even after years of preventive measures. Our data suggest that continual spillover of the novel genetic variant of GOUV and the new genetic lineage of HTNV are responsible for the high prevalence of HFRS in humans. In addition, this is the first report of GOUV associated with human HFRS cases, and our data suggest that GOUV is now the major cause of HFRS in this region.

Background: The development of diabetic angiopathy is associated with profound vascular endothelial cells (VEC) dysfunction and apoptosis. Glycated low density lipoproteins (gly-LDL) continuously produced in the setting of diabetic patients play an important role in causing VEC dysfunction and apoptosis. However, the underlying molecular mechanism remains largely elusive. Protein L-isoaspartyl methyltransferase (PIMT) is a widely expressed protein repair enzyme by multiple cell types of arterial wall including VEC. Our previous proteomic studies showed that the expression of PIMT was significantly decreased in the aorta of diabetic rats as compared with control rats and treatment with grape seed procyanidin extracts significantly increased the PIMT expression in diabetic rats. We hypothesized that PIMT plays a critical role in gly-LDL induced VEC apoptosis; grape seed procyanidin B2 (GSPB2) protect against gly-LDL induced VEC apoptosis through PIMT regulation., Methods and Results: HUVEC transfected negative control and PIMT siRNA were treated with or without GSPB2 (10 µmol/L) for 48 h. Moreover, HUVEC of PIMT overexpression were stimulated by gly-LDL (50 µg/ml) in the presence or absence of GSPB2 (10 µmol/L) for 48 h. Our results showed that gly-LDL downregulated PIMT expression and PIMT overexpression or GSPB2 significantly attenuated gly-LDL induced VEC apoptosis. PIMT siRNA increased VEC apoptosis with up-regulation of p53, cytochrome c release, caspase-9 and caspase-3 activation. Mechanistically, overexpression of PIMT or GSPB2 increased the phosphorylation of ERK1/2 and GSK3β in the gly-LDL induced VEC., Conclusion: In summary, our study identified PIMT as a key player responsible for gly-LDL induced VEC apoptosis and GSPB2 protect against gly-LDL induced VEC apoptosis by PIMT up-regulation. Targeting PIMT including use of GSPB2 could be turned into clinical application in the fighting against diabetic vascular complications.

Hantaviruses are among the most important zoonotic pathogens of humans and the subject of heightened global attention. Despite the importance of hantaviruses for public health, there is no consensus on their evolutionary history and especially the frequency of virus-host co-divergence versus cross-species virus transmission. Documenting the extent of hantavirus biodiversity, and particularly their range of mammalian hosts, is critical to resolving this issue. Here, we describe four novel hantaviruses (Huangpi virus, Lianghe virus, Longquan virus, and Yakeshi virus) sampled from bats and shrews in China, and which are distinct from other known hantaviruses. Huangpi virus was found in Pipistrellus abramus, Lianghe virus in Anourosorex squamipes, Longquan virus in Rhinolophus affinis, Rhinolophus sinicus, and Rhinolophus monoceros, and Yakeshi virus in Sorex isodon, respectively. A phylogenetic analysis of the available diversity of hantaviruses reveals the existence of four phylogroups that infect a range of mammalian hosts, as well as the occurrence of ancient reassortment events between the phylogroups. Notably, the phylogenetic histories of the viruses are not always congruent with those of their hosts, suggesting that cross-species transmission has played a major role during hantavirus evolution and at all taxonomic levels, although we also noted some evidence for virus-host co-divergence. Our phylogenetic analysis also suggests that hantaviruses might have first appeared in Chiroptera (bats) or Soricomorpha (moles and shrews), before emerging in rodent species. Overall, these data indicate that bats are likely to be important natural reservoir hosts of hantaviruses.

The cytokinin oxidase/dehydrogenase (CKX) gene plays a principal role in controlling cytokinin levels and has been shown to be a major quantitative trait locus (QTL) affecting grain number in rice. However, the function and evaluation of the haplotypes of the wheat CKX gene have yet to be illustrated. In this study, TaCKX6-D1, a wheat ortholog of rice OsCKX2, was cloned and its haplotype variants were determined to be significantly associated with the 1000-grain weight on the basis of linkage mapping, association analysis and gene expression analysis. Five TaCKX6-D1 haplotypes, designated a-e, were identified. An indel marker was developed to identify haplotype a, which was associated with higher grain weight. Haplotype a showed decreased expression relative to haplotype b in seeds at 8 d after pollination. Sequence variations among modern cultivars, landraces and wild species suggest a significant domestication signature at the TaCKX6-D1 locus in Chinese wheat germplasm. TaCKX6-D1 may serve as a useful gene for the breeding of high-yielding wheat. A strategy for allele mining and utilization of TaCKX6-D1 was proposed. Our study also sheds light on the mechanisms of grain development and domestication of wheat, as well as the functional divergence of orthologs in comparative genomics., (© 2012 Institute of Crop Sciences. CAAS New Phytologist © 2012 New Phytologist Trust.)

Objective: Age-related aortic stiffness is an independent risk factor for cardiovascular diseases. Although oxidative stress is implicated in aortic stiffness, the underlying molecular mechanisms remain unelucidated. Here, we examined the source of oxidative stress in aging and its effect on smooth muscle cell (SMC) function and aortic compliance using mutant mouse models., Methods and Results: Pulse wave velocity, determined using Doppler, increased with age in superoxide dismutase 2 (SOD2)+/- but not in wild-type, p47phox-/- and SOD1+/- mice. Echocardiography showed impaired cardiac function in these mice. Increased collagen I expression, impaired elastic lamellae integrity, and increased medial SMC apoptosis were observed in the aortic wall of aged SOD2+/- versus wild-type (16-month-old) mice. Aortic SMCs from aged SOD2+/- mice showed increased collagen I and decreased elastin expression, increased matrix metalloproteinase-2 expression and activity, and increased sensitivity to staurosporine-induced apoptosis versus aged wild-type and young (4-month-old) SOD2+/- mice. Smooth muscle α-actin levels were increased with age in SOD2+/- versus wild-type SMCs. Aged SOD2+/- SMCs had attenuated insulin-like growth factor-1-induced Akt and Forkhead box O3a phosphorylation and prolonged tumor necrosis factor-α-induced Jun N-terminal kinase 1 activation. Aged SOD2+/- SMCs had increased mitochondrial superoxide but decreased hydrogen peroxide levels. Finally, dominant-negative Forkhead box O3a overexpression attenuated staurosporine-induced apoptosis in aged SOD2+/- SMCs., Conclusion: Mitochondrial oxidative stress over a lifetime causes aortic stiffening, in part by inducing vascular wall remodeling, intrinsic changes in SMC stiffness, and aortic SMC apoptosis.

Background: Atherosclerosis is one of the major complications of type 2 diabetic patients (T2DM), leading to morbidity and mortality. Grape seed procyanidin B2 (GSPB2) has demonstrated protective effect against atherosclerosis, which is believed to be, at least in part, a result of its antioxidative effects. The aim of this study is to identify the target protein of GSPB2 responsible for the protective effect against atherosclerosis in patients with DM., Methods and Results: GSPB2 (30 mg/kg body weight/day) were administrated to db/db mice for 10 weeks. Proteomics of the aorta extracts by iTRAQ analysis was obtained from db/db mice. The results showed that expression of 557 proteins were either up- or down-regulated in the aorta of diabetic mice. Among those proteins, 139 proteins were normalized by GSPB2 to the levels comparable to those in control mice. Among the proteins regulated by GSPB2, the milk fat globule epidermal growth factor-8 (MFG-E8) was found to be increased in serum level in T2DM patients; the serum level of MFG-E8 was positively correlated with carotid-femoral pulse wave velocity (CF-PWV). Inhibition of MFG-E8 by RNA interference significantly suppressed whereas exogenous recombinant MFG-E8 administration exacerbated atherogenesis the db/db mice. To gain more insights into the mechanism of action of MFG-E8, we investigated the effects of MFG-E8 on the signal pathway involving the extracellular signal-regulated kinase (ERK) and monocyte chemoattractant protein-1 (MCP-1). Treatment with recombinant MFG-E8 led to increased whereas inhibition of MFG-E8 to decreased expression of MCP-1 and phosphorylation of ERK1/2., Conclusion: Our data suggests that MFG-E8 plays an important role in atherogenesis in diabetes through both ERK and MCP-1 signaling pathways. GSPB2, a well-studied antioxidant, significantly inhibited the arterial wall changes favoring atherogenesis in db/db mice by down-regulating MFG-E8 expression in aorta and its serum level. Measuring MFG-E8 serum level could be a useful clinical surrogate prognosticating atherogenesis in DM patients.

Background and Purpose: There is much evidence supporting the role of β₂-adrenoceptors (β₂AR) in angiogenesis but the mechanisms underlying their effects have not been elucidated. Hence, we studied post-ischaemic angiogenesis in the hindlimb (HL) of β₂AR knock-out mice (β₂AR-/-) in vivo and explored possible molecular mechanisms in vitro., Experimental Approach: Femoral artery resection (FAR) was performed in wild-type and β₂AR-/- mice and adaptive responses to chronic HL ischaemia were explored; blood flow was measured by ultrasound and perfusion of dyed beads, bone rarefaction, muscle fibrosis and skin thickness were evaluated by immunoflourescence and morphometric analysis. Intrafemoral delivery of an adenovirus encoding the human β₂AR (ADβ₂AR) was used to reinstate β₂ARs in β₂AR-/- mice. Molecular mechanisms were investigated in mouse-derived aortic endothelial cells (EC) in vitro, focusing on NFκB activation and transcriptional activity., Results: Angiogenesis was severely impaired in β₂AR-/- mice subjected to FAR, but was restored by gene therapy with ADβ₂AR. The proangiogenic responses to a variety of stimuli were impaired in β₂AR-/- EC in vitro. Moreover, removal of β₂ARs impaired the activation of NFκB, a transcription factor that promotes angiogenesis; neither isoprenaline (stimulates βARs) nor TNFα induced NFκB activation in β₂AR(-/-) EC. Interestingly, cAMP response element binding protein (CREB), a transcription factor that counter regulates NFκB, was constitutively increased in β₂AR(-/-) ECs. ADβ₂AR administration restored β₂AR membrane density, reduced CREB activity and reinstated the NFκB response to isoprenaline and TNFα., Conclusions and Implications: Our results suggest that β₂ARs control angiogenesis through the tight regulation of nuclear transcriptional activity., (© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.)

Objective: To evaluate the effectiveness of universal salt iodization (USI) for the control of IDD in Hebei province since it was implemented in 1995, identify the problems currently encountered in the implementation of USI and provide practical proposals for addressing these problems., Methods: Probability proportionate to size sampling (PPS) was employed in the surveillance of IDD, for which a total of 1200 school children aged 8-10 years were randomly selected from 30 counties around the whole province during each IDD survey. The iodine content of salt was determined quantitatively with the titration method. The iodine content of urinary samples was measured by the method of ammonium persulfate oxidation., Results: The coverage of iodized salt increased from 65.0% in 1995 to 98.0% in 1999, then decreased to 88.1% in 2005 which was below the national standard of 90%. The median urinary iodine of children aged 8-10 years varied between 160.1 microg/L and 307.4 microg/L, which was above the national standard. The proportion of urinary samples with iodine content above 300 microg/L was over 30% in 2005, implying exorbitant iodine nutrition among the children. The goiter rate (TGR) among children aged 8-10 years dropped from 11.8% in 1995 to 2.7% in 2005, indicating that the spread of endemic goiter was under control., Conclusion: Preliminary elimination of IDD was achieved by USI in Hebei province. Nevertheless, some problems still existed in USI such as non-iodized salt competition, over iodization and un-standardized iodization. In order to address these problems, the management and supervision of salt market needs to be strengthened to prevent non-iodized salt from reaching households; updating equipment and modifying techniques are also necessary to ensure the quality of iodized salt; to clarify the causes of excessive urinary iodine content, the various sources of iodine from the diet need to be investigated in the future.

Knowledge about the physiologic and pathophysiologic roles of tumor necrosis factor-alpha (TNF-alpha) in acute myocardial ischemia/infarction is still very limited. Evidence implies that TNF-alpha is involved in neural activity including nociception in peripheral and central nervous system. Current study was designed to examine the association of change in TNF-alpha and its mRNA in upper thoracic dorsal root ganglia and spinal cord (T1-T5) during acute myocardial ischemia/infarction induced by coronary artery occlusion (CAO) in rats. The experiment was performed using immunohistochemistry, enzyme immunoassay, in situ hybridization and real time reverse transcription-polymerase chain reaction techniques. At 0.5h, 1h, 3h and 6h of acute myocardial ischemia/infarction, TNF-alpha was mainly up-regulated in a sub-population of small and medium neurons and satellite cells in the dorsal root ganglia (DRG) and spinal neurons, mainly in laminae I, II and V, VI of the spinal dorsal horn of upper thoracic segments. The up-regulation of TNF-alpha mRNA was observed at 30min of CAO, which was statistically significant, compared with the control and the sham surgery groups (P<0.01). The TNF-alpha mRNA was located in the satellite cells and afferent neurons of the DRG and spinal neurons, located mainly in laminae II-VI. The findings indicate an association of up-regulation of TNF-alpha in DRG and spinal cord with acute myocardial ischemia/infarction, suggesting that TNF-alpha may be associated with the nociception initiated by acute myocardial ischemia/infarction, while the pathophysiological role needs to be studied.

The frequency and distribution of the major vernalization requirement genes and their effects on growth habits were studied. Of the 551 bread wheat genotypes tested, seven allelic combinations of the three Vrn-1 genes were found to be responsible for the spring habit, three for the facultative habit and one for the winter habit. The three Vrn-1 genes behaved additively with the dominant allele of Vrn-A1 exerting the strongest effect. The allele combinations of the facultative genotypes and the discovery of spring genotypes with "winter" allele of Vrn-1 implied the presence of as yet unidentified alleles/genes for vernalization response. The dominant alleles of the three Vrn-1 genes were found in all ten ecological regions where wheat is cultivated in China, with Vrn-D1 as the most common allele in nine and Vrn-A1 in one. The combination of vrn-A1vrn-B1Vrn-D1 was the predominant genotype in seven of the regions. Compared with landraces, improved varieties contain a higher proportion of the spring type. This was attributed by a higher frequency of the dominant Vrn-A1 and Vrn-B1 alleles in the latter. Correlations between Vrn-1 allelic constitutions and heading date, spike length, plant type as well as cold tolerance were established.

G protein-coupled receptor kinase 5 (GRK5) is present in endothelial cells (ECs) and has the potential to regulate EC function through seven transmembrane-spanning receptor (7TMR) signaling. Recently, it has been appreciated that GRKs can affect receptor tyrosine kinases (RTKs). VEGF, an RTK, is one of the most potent mediators for EC function and angiogenesis; therefore, we determined the role GRK5 plays in VEGF signaling in human coronary artery ECs (HCAECs). GRK5 levels were increased by VEGF treatment in HCAECs. Adenoviral overexpression of GRK5 inhibited migration and proliferation of HCAECs in response to VEGF. GRK5 overexpression in HCAECs significantly suppressed both acute and late activation of Akt and extracellular signal-related kinase (ERKs) as well as the phosphorylation of GSK-3beta, an endogenous substrate of Akt. Coimmunoprecipitations revealed that GRK5 is physically associated with Akt. This study shows for the first time that GRK5 negatively regulates VEGF signaling in HCAECs and suggests that targeted intervention of GRK5 in ECs might be a novel therapeutic strategy to prevent and treat disorders involving altered EC function.

G protein-coupled receptor kinase 2 (GRK2) is a serine/theorinine kinase that phosphorylates and desensitizes agonist-bound G protein-coupled receptors. GRK2 is increased in expression and activity in lymphocytes and vascular smooth muscle (VSM) in human hypertension and animal models of the disease. Inhibition of GRK2 using the carboxyl-terminal portion of the protein (GRK2ct) has been an effective tool to restore compromised beta-adrenergic receptor (AR) function in heart failure and improve outcome. A well-characterized dysfunction in hypertension is attenuation of betaAR-mediated vasodilation. Therefore, we tested the role of inhibition of GRK2 using GRK2ct or VSM-selective GRK2 gene ablation in a renal artery stenosis model of elevated blood pressure (BP) [the two-kidney, one-clip (2K1C) model]. Use of the 2K1C model resulted in a 30% increase in conscious BP, a threefold increase in plasma norepinephrine levels, and a 50% increase in VSM GRK2 mRNA levels. BP remained increased despite VSM-specific GRK2 inhibition by either GRK2 knockout (GRK2KO) or peptide inhibition (GRK2ct). Although betaAR-mediated dilation in vivo and in situ was enhanced, alpha(1)AR-mediated vasoconstriction was also increased. Further pharmacological experiments using alpha(1)AR antagonists revealed that GRK2 inhibition of expression (GRK2KO) or activity (GRK2ct) enhanced alpha(1D)AR vasoconstriction. This is the first study to suggest that VSM alpha(1D)ARs are a GRK2 substrate in vivo.

More than 30% of the US population has high blood pressure (BP), and less than a third of people treated for hypertension have it controlled. In addition, the etiology of most high BP is not known. Having a better understanding of the mechanisms underlying hypertension could potentially increase the effectiveness of treatment. Because G(q) signaling mediates vasoconstriction and vascular function can cause BP abnormalities, we were interested in determining the role of vascular smooth muscle (VSM) G(q) signaling in two divergent models of hypertension: a renovascular model of hypertension through renal artery stenosis and a genetic model of hypertension using mice with VSM-derived high BP. Inhibition of VSM G(q) signaling attenuated BP increases induced by renal artery stenosis to a similar extent as losartan, an ANG II receptor blocker and current antihypertensive therapy. Inhibition of G(q) signaling also attenuated high BP in our genetic VSM-derived hypertensive model. In contrast, BP remained elevated 25% following treatment with losartan, and prazosin, an alpha(1)-adrenergic receptor antagonist, only decreased BP by 35%. Inhibition of G(q) signaling attenuated VSM reactivity to ANG II and resulted in a 2.4-fold rightward shift in EC(50). We also determined that inhibition of G(q) signaling was able to reverse VSM hypertrophy in the genetic VSM-derived hypertensive model. These results suggest that G(q) signaling is an important signaling pathway in two divergent models of hypertension and, perhaps, optimization of antihypertensive therapy could occur with the identification of particular G(q)-coupled receptors involved.

Objective: To investigate the cardioprotective effects of cariporide as an adjunct in different cardioplegic solutions., Methods: The hearts of 32 young New Zealand rabbits were isolated, hung on the Langendorff perfusion apparatus, arrested with 4 degrees C cardioplegic solutions to cause cardiac ischemia for 120 min, reperfused with 37 degrees C Krebs-Henseleit solution, and randomly divided into 4 equal groups: St. Thomas cardioplegic solution group (perfused with St. Thomas cardioplegic solution every 30 min), histidine-tryptophane-ketoglutarate (HTK) cardioplegic solution group (perfused with HTK solution, St. Thomas solution + cariporide (St + C) group (perfused with St. Thomas cardioplegic solution plus cariporide), and HTK solution plus cariporide (HTK + C) group (perfused with HTK cardioplegic solution plus cariporide). Multichannel physiological record instrument was used to record the left ventricular functions: left ventricular diastolic pressure (LVDP), maximum change rate of left ventricular systolic pressure rise and fall (+dp/dt(max)), maximum change rate of left ventricular diastolic pressure rise and fall (-dp/dt(max)), and coronary flow (CF). Automatic biochemical analyzer was used to measure the creatine kinase (CK)-MB, Then the level of ATP in the cardiac muscle cells was detected by high pressure liquid chromatography, the content of malonyldialdehyde (MDA) was detect by sulfur barbituric acid method. The calcium content (iCa) was measured by atomic absorption spectrophotometry. And the myocardial water content (WC) was measured too., Results: The LVDP, +dp/dt(max), -dp/dt(max), CF recovery rate, and ATP content of the HTK group were all significantly higher than those of the St. Thomas group (all P < 0.05), and the CK-MB, MDA, WC, and iCa of the HTK group were all significantly lower than those of the St. Thomas group (all P < 0.05). The ATP level of the HTK + C group was significantly higher than those of the HTK and St + C groups (both P < 0.05), and the CK-MB, WC, MDA, and iCa of the HTK + C group were all lower than those of the HTK and St + C groups (all P < 0.05). The MDA level of the St + C group was significantly higher than that of the HTK group, and the ATP of the St + C group was significantly lower than that of the HTK group (both P < 0.05), however, there was no significant differences in CK-MB, WC, and iCa between these 2 groups (all P > 0.05)., Conclusion: Cariporide enhances the cardioprotective effects of the St. Thomas and HTK cardioplegic solutions in immature myocardium.

Recent studies from our lab and others have shown that the hematopoietic cytokine erythropoietin (EPO) can protect the heart from ischemic damage in a red blood cell-independent manner. Here we examined any protective effects of the long-acting EPO analog darbepoetin alfa (DA) in a rat model of ischemia-reperfusion (I/R) injury. Rats were subjected to 30-min ischemia followed by 72-h reperfusion. In a dose-response study, DA (2, 7, 11, and 30 mug/kg) or vehicle was administered as a single bolus at the start of ischemia. To determine the time window of potential cardioprotection, a single high dose of DA (30 mug/kg) was given at either the initiation or the end of ischemia or at 1 or 24 h after reperfusion. After 3 days, cardiac function and infarct size were assessed. Acute myocyte apoptosis was quantified by TUNEL staining on myocardial sections and by caspase-3 activity assays. DA significantly reduced infarct size from 32.8 +/- 3.5% (vehicle) to 11.0 +/- 3.3% in a dose-dependent manner, while there was no difference in ischemic area between groups. Treatment with DA as late as 24 h after the beginning of reperfusion still demonstrated a significant reduction in infarct size (17.0 +/- 1.6%). Consistent with infarction data, DA improved in vivo cardiac reserve compared with vehicle. Finally, DA significantly decreased myocyte apoptosis and caspase-3 activity after I/R. These data indicate that DA protects the heart against I/R injury and improves cardiac function, apparently through a reduction of myocyte apoptosis. Of clinical importance pointing toward a relevant therapeutic utility, we report that even if given 24 h after I/R injury, DA can significantly protect the myocardium.