Publications by authors named "Kai Kang"

233 Publications

Remote nursing training model combined with proceduralization in the intensive care unit dealing with patients with COVID-19.

World J Clin Cases 2021 Feb;9(5):999-1004

Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China.

The shortage of personal protective equipment and lack of proper nursing training have been endangering health care workers dealing with coronavirus disease 2019 (COVID-19). In our treatment center, the implementation of a holistic care model of time-sharing management for severe and critical COVID-19 patients has further aggravated the shortage of intensive care unit (ICU) professional nurses. Therefore, we developed a short-term specialized and targeted nursing training program to help ICU nurses to cope with stress and become more efficient, thus reducing the number of nurses required in the ICU. In order to avoid possible human-to-human spread, small teaching classes and remote training were applied. The procedural training mode included four steps: preparation, plan, implementation, and evaluation. An evaluation was conducted throughout the process of nursing training. In this study, we documented and shared experiences in transitioning from traditional face-to-face programs to remote combined with proceduralization nursing training mode from our daily work experiences during the COVID-19 pandemic, which has shown to be helpful for nurses working in the ICU.
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http://dx.doi.org/10.12998/wjcc.v9.i5.999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896662PMC
February 2021

Loganin Attenuates Septic Acute Renal Injury with the Participation of AKT and Nrf2/HO-1 Signaling Pathways.

Drug Des Devel Ther 2021 11;15:501-513. Epub 2021 Feb 11.

Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, Heilongjiang 150001, People's Republic of China.

Purpose: Sepsis, a destructive inflammatory response syndrome, is the principal reason to induce death in the intensive care unit. Loganin has been proved to possess the property of anti-inflammation, antioxidant, neuroprotection, and sedation. The primary aim of this study was to evaluate whether Loganin could alleviate acute kidney injury (AKI) during sepsis and investigate the latent mechanisms.

Methods: Septic AKI models were established by cecal ligation and puncture (CLP) surgery in mice and given Loganin (20, 40, 80 mg/kg) by gavage. Lipopolysaccharides (LPS)-stimulated human kidney proximal tubular (HK2) cells incubated in Loganin (5, 10, 20 μ M) were used to explore the accurate mechanisms. Survival rate, renal function (creatinine and blood urea nitrogen), and renal pathological changes were detected in septic mice. Oxidative stress markers (SOD, GSH-Px, MDA, and SOD), mitochondrial membrane potential, mitochondrial calcium overload, and nuclear factor E2-related factor 2 (Nrf2)/heme-oxygenase 1 (HO-1) pathway activation in vivo and in vitro were determined by commercial kits and Western blot. Cell apoptosis, apoptotic-related protein (cleaved caspase-3, Bcl-2, and Bax) expression and protein kinase B (AKT) phosphorylation in vivo and in vitro were measured by TUNEL staining and Western blot. Finally, AKT blockage by 10 μM LY294002 or Nrf2 inhibition by10 μ M ML385 were utilized to prove the involvement of AKT and Nrf2/HO-1 pathway in AKI during sepsis.

Results: We found Loganin treatment (20, 40, 80 mg/kg) mitigated septic AKI reflected by elevated renal function and palliative pathological changes. Oxidative stress and apoptosis in the kidney and LPS-treated HK2 cells were also inhibited by Loganin administration, which was accompanied by AKT and Nrf2/HO-1 pathway activation. Besides, the protective effects of Loganin could be diminished by AKT or Nrf2 blockage, indicating the involvement of AKT and Nrf2/HO-1 pathway.

Conclusion: The results suggested that the protective effects of Loganin on AKI during sepsis might be mediated by AKT and Nrf2/HO-1 pathway signaling activation in kidney proximal tubular cells.
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http://dx.doi.org/10.2147/DDDT.S294266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886113PMC
February 2021

Correction to: Central Blockade of E-Prostanoid 3 Receptor Ameliorated Hypertension Partially by Attenuating Oxidative Stress and Inflammation in the Hypothalamic Paraventricular Nucleus of Spontaneously Hypertensive Rats.

Cardiovasc Toxicol 2021 Feb 5. Epub 2021 Feb 5.

Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine; Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an Jiaotong University, Xi'an, 710061, China.

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http://dx.doi.org/10.1007/s12012-021-09634-5DOI Listing
February 2021

Chronic Infusion of Astaxanthin Into Hypothalamic Paraventricular Nucleus Modulates Cytokines and Attenuates the Renin-Angiotensin System in Spontaneously Hypertensive Rats.

J Cardiovasc Pharmacol 2021 Feb;77(2):170-181

Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an, China.

Abstract: Oxidative stress, the renin-angiotensin system (RAS), and inflammation are some of the mechanisms involved in the pathogenesis of hypertension. The aim of this study is to examine the protective effect of the chronic administration of astaxanthin, which is extracted from the shell of crabs and shrimps, into hypothalamic paraventricular nucleus (PVN) in spontaneously hypertensive rats. Animals were randomly assigned to 2 groups and treated with bilateral PVN infusion of astaxanthin or vehicle (artificial cerebrospinal fluid) through osmotic minipumps (Alzet Osmotic Pumps, Model 2004, 0.25 μL/h) for 4 weeks. Spontaneously hypertensive rats had higher mean arterial pressure and plasma level of norepinephrine and proinflammatory cytokine; higher PVN levels of reactive oxygen species, NOX2, NOX4, IL-1β, IL-6, ACE, and AT1-R; and lower PVN levels of IL-10 and Cu/Zn SOD, Mn SOD, ACE2, and Mas receptors than Wistar-Kyoto rats. Our data showed that chronic administration of astaxanthin into PVN attenuated the overexpression of reactive oxygen species, NOX2, NOX4, inflammatory cytokines, and components of RAS within the PVN and suppressed hypertension. The present results revealed that astaxanthin played a role in the brain. Our findings demonstrated that astaxanthin had protective effect on hypertension by improving the balance between inflammatory cytokines and components of RAS.
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http://dx.doi.org/10.1097/FJC.0000000000000953DOI Listing
February 2021

Joint Hidden Markov Model for Longitudinal and Time-to-Event Data with Latent Variables.

Multivariate Behav Res 2021 Jan 7:1-17. Epub 2021 Jan 7.

Department of Statistics, Chinese University of Hong Kong.

This study develops a new joint modeling approach to simultaneously analyze longitudinal and time-to-event data with latent variables. The proposed model consists of three components. The first component is a hidden Markov model for investigating a longitudinal observation process and its underlying transition process as well as their potential risk factors and dynamic heterogeneity. The second component is a factor analysis model for characterizing latent risk factors through multiple observed variables. The third component is a proportional hazards model for examining the effects of observed and latent risk factors on the hazards of interest. A shared random effect is introduced to allow the longitudinal and time-to-event outcomes to be correlated. A Bayesian approach coupled with efficient Markov chain Monte Carlo methods is developed to conduct statistical inference. The performance of the proposed method is evaluated through simulation studies. An application of the proposed model to a general health survey study concerning cognitive impairment and mortality for Chinese elders is presented.
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http://dx.doi.org/10.1080/00273171.2020.1865864DOI Listing
January 2021

Antihypertensive effects of exercise involve reshaping of gut microbiota and improvement of gut-brain axis in spontaneously hypertensive rat.

Gut Microbes 2021 Jan-Dec;13(1):1-24

Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China , Xi'an China.

Exercise (Ex) has long been recognized to produce beneficial effects on hypertension (HTN). This coupled with evidence of gut dysbiosis and an impaired gut-brain axis led us to hypothesize that reshaping of gut microbiota and improvement in impaired gut-brain axis would, in part, be associated with beneficial influence of exercise. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise for 12 weeks, whereas, detrained groups underwent 8 weeks of moderate-intensity exercise followed by 4 weeks of detraining. Fecal microbiota, gut pathology, intestinal inflammation, and permeability, brain microglia and neuroinflammation were analyzed. We observed that exercise training resulted in a persistent decrease in systolic blood pressure in the SHR. This was associated with increase in microbial α diversity, altered β diversity, and enrichment of beneficial bacterial genera. Furthermore, decrease in the number of activated microglia, neuroinflammation in the hypothalamic paraventricular nucleus, improved gut pathology, inflammation, and permeability were also observed in the SHR following exercise. Interestingly, short-term detraining did not abolish these exercise-mediated improvements. Finally, fecal microbiota transplantation from exercised SHR into sedentary SHR resulted in attenuated SBP and an improved gut-brain axis. These observations support our concept that an impaired gut-brain axis is linked to HTN and exercise ameliorates this impairment to induce antihypertensive effects.
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http://dx.doi.org/10.1080/19490976.2020.1854642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781639PMC
December 2020

Holistic care model of time-sharing management for severe and critical COVID-19 patients.

World J Clin Cases 2020 Nov;8(22):5513-5517

Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China.

The rapid global outbreak of coronavirus disease 2019 (COVID-19) and the surge of infected patients have led to the verge of exhaustion of critical care medicine resources worldwide, especially with regard to critical care staff. A holistic care model on time-sharing management for severe and critical COVID-19 patients is proposed, which includes formulation of individualized care objectives and plans, identification of care tasks in each shift and making detailed checklist, and management of quality of care. This study was conducted in the COVID-19 treatment center of Harbin, Heilongjiang Province. The data collected from the treatment center were recorded and analyzed. From the results we can deduce that it is especially suitable for non-intensive care unit (non-ICU) nurses to adapt care management mode of ICU as soon as possible and ensure the quality and efficiency of care during the epidemic. The holistic care model on time-sharing management for severe and critical cases with COVID-19 proposed based on our daily work experiences can assist in improving the quality and efficiency of care, thus reducing the mortality rate of patients in ICU.
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http://dx.doi.org/10.12998/wjcc.v8.i22.5513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716320PMC
November 2020

Corrigendum to: iASPP protects the heart from ischemia injury by inhibiting p53 expression and cardiomyocyte apoptosis.

Acta Biochim Biophys Sin (Shanghai) 2020 Dec 18. Epub 2020 Dec 18.

Department of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education) at College of Pharmacy, Harbin Medical University, Harbin 150086, China.

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http://dx.doi.org/10.1093/abbs/gmaa168DOI Listing
December 2020

Up-regulation of miR-137 can inhibit PTN in target manner to regulate PTN/PTPRZ pathway to prevent cognitive dysfunction caused by propofol.

Am J Transl Res 2020 15;12(11):7490-7500. Epub 2020 Nov 15.

Anesthesiology Department, The First Affiliated Hospital of Dalian Medical University Dalian City, Liaoning Province, China.

Objective: To explore the effects of miR-137 on cognitive dysfunction in rats induced by propofol (PRO).

Methods: Male SD rats and SK-N-SH cells were purchased, and control and PRO groups were set up in the rats, and the same groups were set up in the cells. On the basis of the PRO group, miR-137 and PTN were up-regulated or down-regulated, and cognitive dysfunction and cell biological functions in each group were detected.

Results: The cognitive function of rats induced by PRO might be affected. We observed that the escape latency of PRO group was significantly prolonged, with significantly lower percentage of time for target platform exploration and times of crossing the platform, while over-expression of miR-137 or knock down of PTN could change the above results. Under PRO intervention, the expression of miR-137 in SK-N-SH cells decreased in a dose-dependent manner, while the expression and protein level of PTN in SK-N-SH cells increased in a dose-dependent manner. Cytotoxicity test yielded a 30 μM concentration of PRO as the optimal experimental concentration. When miR-137 and PTN were up-regulated or down-regulated, PRO-induced cell apoptosis, proliferation and PTN/PTPRZ pathway protein phosphorylation level were effectively reversed. Dual luciferase reporter confirmed that miR-137 and PTN have targeted relationship.

Conclusion: Up-regulation of miR-137 can at least partially regulate PTN/PTPRZ pathway through the inhibition of PTN in a targeted manner, effectively inhibit cell apoptosis, and protect cognitive dysfunction caused by PRO.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724353PMC
November 2020

Pathogenesis of liver injury in Takayasu arteritis: advanced understanding leads to new horizons.

J Int Med Res 2020 Dec;48(12):300060520972222

Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang, China.

Liver injury in Takayasu arteritis (TA) is a rare phenomenon. Most symptoms are nonspecific, and the exact pathogenesis remains to be elucidated. Early diagnosis and new treatment methods are important for an improved prognosis. A summary of the clinical information and mechanistic analyses may contribute to making an early diagnosis and development of new treatment methods. A PubMed search was conducted using the specific key words "Takayasu arteritis" and "liver" or "hepatitis" or "hepatic". Symptoms and treatment of TA with an accompanying liver injury were reviewed retrospectively. Many factors are presumed to be involved in the mechanism of TA with liver injury, including the immune response, genes, infections, and gut microbiota. There are several lines of evidence indicating that immune dysfunction is the main pathogenic factor that triggers granuloma formation in TA patients. However, the role of genetics and infections has not been fully confirmed. Recently, the gut microbiota has emerged as an essential component in the process. We reviewed in detail the current concepts that support the complex pathogenesis of TA accompanied by liver injury, and we presented recent theories from the literature. Finally, we discussed future research directions of liver injury in TA.
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http://dx.doi.org/10.1177/0300060520972222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720339PMC
December 2020

General and fast synthesis of graphene frameworks using sugars for high-performance hydrogen peroxide nonenzymatic electrochemical sensor.

Mikrochim Acta 2020 Nov 20;187(12):669. Epub 2020 Nov 20.

School of Pharmaceutical Sciences, Key Laboratory of Innovative Drug Development and Evaluation, Hebei Medical University, Shijiazhuang, 050017, People's Republic of China.

3D graphene frameworks (GFs) are fast and scalably synthesized via a general and facile method from the rich biomass of sugars with the aid of molten salts, using glucose as the prototype, to obtain an effective sensing platform for sensitive nonenzymatic hydrogen peroxide (HO) detection. The electroactive area of the GFs/GCE (0.1437 cm) is obviously higher than that of bare GCE (0.0653 cm). The GFs are found to exhibit remarkable electrocatalytic activity toward HO reduction while avoiding enzyme loading. The electrochemical sensor for HO based on GFs displays a low detection limit of 0.032 ± 0.005 μM (S/N = 3) at a working potential of - 0.55 V in 0.01 M N-saturated phosphate-buffered saline (PBS, pH = 7.4) by an amperometric method. The sensor has good selectivity over other compounds such as ascorbic acid, dopamine, uric acid, NaCl, citric acid, and glucose. Moreover, the sensor shows excellent reproducibility with a relative standard deviation of 3.7% and acceptable stability after 30 days of usage. Furthermore, it can detect HO released from living tumorigenic cells in real time. Most importantly, it is demonstrated that such GFs can be obtained from a variety of sugars (sucrose, fructose, lactose, and maltose). This work may offer a new general avenue for the synthesis of 3D GFs and promote the development of electrochemical sensors. Graphical abstract We have reported a general and fast method to synthesize GFs from sugars (glucose, sucrose, fructose, lactose, and maltose) with the addition of molten NaCO salt as a template. The developed GFs can be applied as excellent electrode materials for efficient electrochemical sensing of HO.
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http://dx.doi.org/10.1007/s00604-020-04607-xDOI Listing
November 2020

Cytokine Storm May Not Be the Chief Culprit for the Deterioration of COVID-19.

Viral Immunol 2020 Nov 17. Epub 2020 Nov 17.

Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.

COVID-19 is spreading and ravaging all over the world, and the number of deaths is increasing day by day without downward trend. However, there is limited knowledge of pathogenesis on the deterioration of COVID-19 at present. In this study we aim to determine whether cytokine storm is really the chief culprit for the deterioration of COVID-19. The confirmed COVID-19 patients were divided into moderate group ( = 89), severe group ( = 37), and critical group ( = 41). Demographic data were collected and recorded on admission to ICU. Clinical data were obtained when moderate, severe, or critical COVID-19 was diagnosed, and then compared between groups. The proportion of enrolled COVID-19 patients was slightly higher among males (52.5%) than females (47.5%), with an average age of 64.87 years. The number of patients without comorbidities exceed one third (36.1%), and patients with 1, 2, 3, 4 kinds of comorbidities accounted for 23.0%, 23.0%, 13.1%, and 4.9%, respectively. IL-6, IL-10, TNF, and IFN-, including oxygenation index, sequential organ failure assessment score, white blood cell count, lymphocyte count, lymphocyte percentage, platelet, C-reaction protein, lactate dehydrogenase, creatine kinase isoenzyme, albumin, D-Dimer, and fibrinogen showed significant difference between groups. Some, but not all, cytokines and chemokines were involved in the deterioration of COVID-19, and thus cytokine storm maybe just the tip of the iceberg and should be used with caution to explain pathogenesis on the deterioration of COVID-19, which might be complex and related to inflammation, immunity, blood coagulation, and multiple organ functions. Future studies should focus on identification of specific signaling pathways and mechanisms after severe acute respiratory syndrome coronavirus 2 infections (IRB number: IRB-AF/SC-04/01.0).
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http://dx.doi.org/10.1089/vim.2020.0243DOI Listing
November 2020

Evaluation of burnout among hospital and health-system pharmacy technicians in North Carolina.

Am J Health Syst Pharm 2020 12;77(24):2041-2042

Premier, Inc. Raleigh, NC.

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http://dx.doi.org/10.1093/ajhp/zxaa315DOI Listing
December 2020

Central Blockade of E-Prostanoid 3 Receptor Ameliorated Hypertension Partially by Attenuating Oxidative Stress and Inflammation in the Hypothalamic Paraventricular Nucleus of Spontaneously Hypertensive Rats.

Cardiovasc Toxicol 2020 Nov 9. Epub 2020 Nov 9.

Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine; Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an Jiaotong University, Xi'an, 710061, China.

Hypertension, as one of the major risk factors for cardiovascular disease, significantly affects human health. Prostaglandin E (PGE) and the E3-class prostanoid (EP3) receptor have previously been demonstrated to modulate blood pressure and hemodynamics in various animal models of hypertension. The PGE2-evoked pressor and biochemical responses can be blocked with the EP3 receptor antagonist, L-798106 (N-[(5-bromo-2methoxyphenyl)sulfonyl]-3-[2-(2-naphthalenylmethyl) phenyl]-2-propenamide). In the hypothalamic paraventricular nucleus (PVN), sympathetic excitation can be introduced by PGE2, which can activate EP3 receptors located in the PVN. In such a case, the central knockdown of EP3 receptor can be considered as a potential therapeutic modality for hypertension management. The present study examined the efficacy of the PVN infusion of L-798106, by performing experiments on spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs). The rats were administered with chronic bilateral PVN infusion of L-798106 (10 μg/day) or the vehicle for 28 days. The results indicated that the SHRs had a higher mean arterial pressure (MAP), an increased Fra-like (Fra-LI) activity in the PVN, as well as a higher expression of gp, mitogen-activated protein kinase (MAPK), and proinflammatory cytokines in the PVN compared with the WKYs. Additionally, the expression of Cu/Zn-SOD in the PVN of the SHRs was reduced compared with the WKYs. The bilateral PVN infusion of L-798106 significantly reduced MAP, as well as plasma norepinephrine (NE) levels in the SHRs. It also inhibited Fra-LI activity and reduced the expression of gp, proinflammatory cytokines, and MAPK, whereas it increased the expression of Cu/Zn-SOD in the PVN of SHRs. In addition, L-798106 restored the balance of the neurotransmitters in the PVN. On the whole, the findings of the present study demonstrate that the PVN blockade of EP3 receptor can ameliorate hypertension and cardiac hypertrophy partially by attenuating ROS and proinflammatory cytokines, and modulating neurotransmitters in the PVN.
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http://dx.doi.org/10.1007/s12012-020-09619-wDOI Listing
November 2020

Mechanisms of Renal-Splenic Axis Involvement in Acute Kidney Injury Mediated by the α7nAChR-NF-κB Signaling Pathway.

Inflammation 2020 Nov 3. Epub 2020 Nov 3.

Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, No.23 Youzheng Street, Harbin, 150001, China.

This study aimed to investigate the effect of splenectomy on dexmedetomidine-activated cholinergic anti-inflammatory pathway-mediated alleviation of LPS-induced AKI. A mouse model of septic kidney injury was established in C57BL/6 mice. A total of 30 C57BL/6 mice were randomly divided into the control group, LPS group, dexmedetomidine + LPS group, splenectomy group, splenectomy + LPS group, and splenectomy + dexmedetomidine + LPS group. The pathological effects in kidney tissues in each group were analyzed by HE staining. Apoptosis in each group was examined by the TUNEL method. Cr and Cys-C levels in each group were measured by ELISA. The expression levels of IL-6, NF-κB p65, Caspase-3, the antiapoptotic protein Bcl-2, the proapoptotic protein Bax, and α7nAChR in each group were measured by qRT-PCR and Western blotting. Dexmedetomidine alone reduced apoptosis in kidney tissue; however, apoptosis was increased after splenectomy in mice treated with dexmedetomidine. Splenectomy reduced the production of proinflammatory cytokines in circulation and had a protective effect on the kidney. Splenectomy inhibited dexmedetomidine-mediated activation of the α7nAChR pathway. Dexmedetomidine effectively alleviated LPS-induced kidney injury, and splenectomy inhibited the anti-inflammatory, antiapoptotic, and renoprotective effects of dexmedetomidine. The kidney-spleen axis is mediated by the α7nAChR-NF-κB signaling pathway and is involved in the development of AKI.
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http://dx.doi.org/10.1007/s10753-020-01374-yDOI Listing
November 2020

iASPP protects the heart from ischemia injury by inhibiting p53 expression and cardiomyocyte apoptosis.

Acta Biochim Biophys Sin (Shanghai) 2021 Jan;53(1):102-111

Department of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education) at College of Pharmacy, Harbin Medical University, Harbin 150086, China.

Currently, there remains a great need to elucidate the molecular mechanism of acute myocardial infarction in order to facilitate the development of novel therapy. Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is a member of the ASPP family proteins and an evolutionarily preserved inhibitor of p53 that is involved in many cellular processes, including apoptosis of cancer cells. The purpose of this study was to investigate the possible role of iASPP in acute myocardial infarction. The protein level of iASPP was markedly reduced in the ischemic hearts in vivo and hydrogen peroxide-exposed cardiomyocytes in vitro. Overexpression of iASPP reduced the infarct size and cardiomyocyte apoptosis of mice subjected to 24 h of coronary artery ligation. Echocardiography showed that cardiac function was improved as indicated by the increase in ejection fraction and fractional shortening. In contrast, knockdown of iASPP exacerbated cardiac injury as manifested by impaired cardiac function, increased infarct size, and apoptosis rate. Mechanistically, overexpression of iASPP inhibited, while knockdown of iASPP increased the expressions of p53 and Bax, the key regulators of apoptosis. Taken together, our results suggested that iASPP is an important regulator of cardiomyocyte apoptosis, which represents a potential target in the therapy of myocardial infarction.
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http://dx.doi.org/10.1093/abbs/gmaa104DOI Listing
January 2021

Zippering DNA Tetrahedral Hyperlink for Ultrasensitive Electrochemical MicroRNA Detection.

Anal Chem 2020 11 29;92(22):15137-15144. Epub 2020 Oct 29.

Pluripotency of a DNA tetrahedron (DNA) has made the iconic framework a compelling keystone in biosensors and biodevices. Herein, distinct from the well-tapped applications in substrate fabrication, we focus on exploring their tracing and signaling potentials. A homologous family of four isostructural DNA, ., DNA, was engineered to form a sensor circuitry, in which a target-specific monolayer of thiolated DNA pinned down the analyte jointly with the reciprocal DNA into a sandwich complex; the latter further rallied an interdigital relay of biotinylated DNA into a microsized hyperlink dubbed polyDNA. Its scale and growth factors were illuminated rudimentarily in transmission electron microscopy and confocal laser scanning microscopy. Using a nonsmall-cell lung cancer-related microRNA (hsa-miR-193a-3p) as the subject, a compound DNA-backboned construct was synthesized, fusing all building blocks together. Its superb tacticity and stereochemical conformality avail the templating of a horseradish peroxidase train, which boosted the paralleled catalytic surge of proton donors, resulting in an attomolar detection limit and a broad calibration range of more than seven orders of magnitude. Such oligomerization bested the conventional hybridization chain reaction laddering at both biomechanical stability and stoichiometric congruency. More significantly, it demonstrates the flexibility of DNA architectures and their multitasking ability in biosensing.
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http://dx.doi.org/10.1021/acs.analchem.0c03553DOI Listing
November 2020

Significance of Tumor Mutation Burden in Immune Infiltration and Prognosis in Cutaneous Melanoma.

Front Oncol 2020 18;10:573141. Epub 2020 Sep 18.

Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Melanoma is highly immunogenic and therefore suitable for immunotherapy, but the efficacy is limited by response rate. In several types of tumor, tumor mutation burden (TMB) and immune infiltration have been reported to predict the response to immunotherapy, although each has its limitations. In the current study, we aimed to explore the association of TMB with immune infiltration and prognosis in cutaneous melanoma. The data of cutaneous melanoma used for analyses was downloaded from The Cancer Genome Atlas (TCGA) database. The mutation data was sorted using "maftools" R package. TMB was estimated and then patients were divided into two groups based on TMB. The association of TMB with prognosis and clinical characteristics was explored. Differential analysis between two TMB groups was performed using "DESeq2" R package to identify differentially expressed genes (DEGs). The function enrichment analyses of DEGs were conducted to screen critical pathways. Besides, DEGs were further filtered to identify two hub genes, based on which a risk score model and nomogram for predicting prognosis were conducted, and the validation was performed using three datasets from Gene Expression Omnibus (GEO) database. Finally, CIBERSORT algorithm and TIMER database were used to assess the effect of TMB and hub genes on immune infiltration. The most common mutation was C > T, and the top three frequently mutated genes were , and . Higher TMB indicated better survival outcomes and lower pathological stages. 735 DEGs were identified and mainly involved in immune-related and adhesion-related pathways. The risk score model and nomogram were validated using receiver operating characteristic (ROC) curves and calibration curves, and exhibited relatively high predictive capability. Decision curve analysis (DCA) was used to assess clinical benefit. As for immune infiltration, the proportion was higher for macrophages M1 and M2 in the high-TMB group, while lower for memory B cells and regulatory T cells. In cutaneous melanoma, TMB was positively correlated with prognosis. The risk score model and nomogram can be conveniently used to predict prognosis. The association of TMB with immune infiltration can help improve the predicting methods for the response to immunotherapy.
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http://dx.doi.org/10.3389/fonc.2020.573141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531222PMC
September 2020

Electrothermal soft manipulator enabling safe transport and handling of thin cell/tissue sheets and bioelectronic devices.

Sci Adv 2020 Oct 16;6(42). Epub 2020 Oct 16.

Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

"Living" cell sheets or bioelectronic chips have great potentials to improve the quality of diagnostics and therapies. However, handling these thin and delicate materials remains a grand challenge because the external force applied for gripping and releasing can easily deform or damage the materials. This study presents a soft manipulator that can manipulate and transport cell/tissue sheets and ultrathin wearable biosensing devices seamlessly by recapitulating how a cephalopod's suction cup works. The soft manipulator consists of an ultrafast thermo-responsive, microchanneled hydrogel layer with tissue-like softness and an electric heater layer. The electric current to the manipulator drives microchannels of the gel to shrink/expand and results in a pressure change through the microchannels. The manipulator can lift/detach an object within 10 s and can be used repeatedly over 50 times. This soft manipulator would be highly useful for safe and reliable assembly and implantation of therapeutic cell/tissue sheets and biosensing devices.
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http://dx.doi.org/10.1126/sciadv.abc5630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567602PMC
October 2020

Targeted galectin-7 inhibition with ultrasound microbubble targeted gene therapy as a sole therapy to prevent acute rejection following heart transplantation in a Rodent model.

Biomaterials 2020 Dec 6;263:120366. Epub 2020 Sep 6.

Department of Cardiology, University of Nebraska Medical Center, Omaha, NE, NE 68198, USA.

Background: Despite significant advances in transplantation, acute cellular rejection (AR) remains a major obstacle that is most prevalent in the first months post heart transplantation (HT). Current treatments require high doses of immunosuppressive drugs followed by maintenance therapies that have systemic side effects including early infection. In this study, we attempted to prevent AR with a myocardial-targeted galectin-7-siRNA delivery method using cationic microbubbles (CMBs) combined with ultrasound targeted microbubble destruction (UTMD) to create local immunosuppression in a rat abdominal heterotopic heart transplantation acute rejection model.

Methods And Results: Galectin-7-siRNA (siGal-7) bound to CMBs were synthesized and effective ultrasound-targeted delivery of siGal-7 into target cells confirmed in vitro. Based on these observations, three transplant rat models were tested:①isograft (ISO); ② Allograft (ALLO) +UTMD; and ③ALLO + PBS. UTMD treatments were administered at 1, 3, 5, 7 days after HT. Galectin 7 expression was reduced by 50% compared to ALLO + PBS (p < 0.005), and this was associated with significant reductions in both galectin 7 and Interleukin-2 protein levels (p < 0.001). The ALLO + UTMD group had Grade II or less inflammatory infiltration and myocyte damage in 11/12 rats using International Society For Heart and Lung Transplantation grading, compared to 0/12 rats with this grading in the ALLO + PBS group at 10 days post HT (p < 0.001).

Conclusions: Ultrasound-targeted galectin-7-siRNA knockdown with UTMD can prevent acute cellular rejection in the early period after allograft heart transplantation without the need for systemic immunosuppression.

Key Words: Microbubble, Acute Rejection, Heart Transplantation, Galectin-7, RNA.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120366DOI Listing
December 2020

Electrochemiluminescence-Repurposed Abiological Catalysts in Full Protein Tag for Ultrasensitive Immunoassay.

Anal Chem 2020 10 29;92(20):14076-14084. Epub 2020 Sep 29.

School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.

Being announced as one of the "2019 Top Ten Emerging Technologies in Chemistry" by IUPAC, the directed evolution of artificial metalloenzymes has led to a broad scope of abiotic processes. Here, inspired by those key proteins in bioluminescence, a rudimentary expression of bio-electrochemiluminescent (ECL) macromolecules was achieved via the complexation of zinc -porphyrin IX (ZnPPIX) within -hemoglobin (-Hb). A high-yield monochromic irradiation at 644 nm could be provoked potentiostatically from the reconstituted -Hb in solutions. Its secondary structure integrity was elucidated by UV and circular dichroism spectrometry, while voltammetry-hyphenated surface plasmon resonance authenticated its ligation conservativeness in electrical fields. Further conjugation with streptavidin rendered a homogeneous Janus fusion of both receptor and reporter domains, enabling a new abiological catalyst-linked ECL bioassay. On the other hand, singular ZnPPIX inside each tetrameric subunit of Hb accomplished an overall signal amplification without the bother of luminogenic heterojunctions. This pH-tolerant and non-photobleaching optics was essentialized to be the unique configuration interaction between Zn and O, by which the direct electrochemistry of proteins catalyzed the transient progression of O → O → O* + υ selectively. Such principle was implemented as a signal-on strategy for the determination of a characteristic cancer biomarker, the vascular endothelial growth factor, resulting in competent performance at a low detection limit of 0.6 pg·mL and a wide calibration range along with good stability and reliability in real practices. This simple mutation repurposed the O-transport Hb in the erythrocytes of almost all vertebrates into a cluster of oxidoreductases with intrinsic ECL activity, which would enrich the chromophore library. More importantly, its genetically engineered variants may come in handy in biomedical diagnosis and visual electrophysiology.
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http://dx.doi.org/10.1021/acs.analchem.0c03114DOI Listing
October 2020

Value of plasma homocysteine to predict stroke, cardiovascular diseases, and new-onset hypertension: A retrospective cohort study.

Medicine (Baltimore) 2020 Aug;99(34):e21541

Department of Geriatrics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

The influences of hyperhomocysteinemia on cardiovascular diseases (CVDs), stroke and new-onset hypertension are unclear. The aim of the study is to explore the associations of homocysteine levels with stroke, CVDs, and new-onset hypertension in Chinese individuals.This retrospective cohort study included outpatients and inpatients from the Department of Geriatrics at Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine from January to December 2000. They were divided based on their homocysteine (Hcy) levels in 2000: Q1 (<10 μmol/L), Q2 (10-15 μmol/L), and Q3 (>15 μmol/L) and according to whether they had hypertension at baseline. Information about stroke, mortality and major adverse cardiac events, and newly onset hypertension was gathered in December each year until 2017. The effects of Hcy levels on the risk for stroke and CVDs among all patients, and new-onset hypertension among patients without hypertension at baseline were evaluated.After adjustment for confounders, compared with the Q1 group (Hcy <10 μmol/L), when the Hcy increased to 10 to 15 μmol/L, the risks for stroke, CVDs, and new-onset hypertension significantly increased, and the hazard ratio and 95% confidence interval were 2.02 (1.35-3.05, P = .001), 2.22 (1.32-3.76, P = .003), and 7.20 (4.52-11.48, P < .001), respectively. Hcy improved the predictive capability of traditional risk factors for stroke. The optimal cut-off value of Hcy for predicting stroke was 13.4 μmol/L (sensitivity: 70.9%, specificity: 62.2%).Hcy 10 to 15 μmol/L is significantly associated with the risks for stroke, mortality and major adverse cardiac events, and hypertension. The best cut-off point of Hcy for predicting stroke is 13.4 μmol/L.
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http://dx.doi.org/10.1097/MD.0000000000021541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447408PMC
August 2020

One-step electrochemical sensor based on an integrated probe toward sub-ppt level Pb detection by fast scan voltammetry.

Anal Chim Acta 2020 Sep 17;1128:174-183. Epub 2020 Jul 17.

State Key Laboratory for Managing Biotic, Chemical Threats to the Quality, Safety of Agro-products, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, 315211, PR China. Electronic address:

Herein, a one-step electrochemical sensor for selective and sensitive detection of lead ion Pb was developed based on an integrated probe meso-tetra(4-carboxyphenyl) porphine (TCPP)-multi-walled carbon nanotubes (MWCNTs)@FeO, which is TCPP-modified magnetic multi-walled carbon nanotubes. In the integrated probe, TCPP is a porphyrin with a specific cavity structure which could selectively chelate with Pb, MWCNTs with good electric conductivity provide a place to load TCPP and form a specific adsorption state of Pb on the electrode surface, and FeO enables the rapid separation and one-step fabrication of the electrochemical sensor. Based on it, the sample pre-enrichment, separation and determination can be integrated, making the whole process very fast and simple. In addition, fast scan voltammetry (FSV) with a scan rate up to 200 V/s could be used to improve the detection sensitivity greatly, benefitting from the specific adsorption state formed. Under the optimal conditions obtained through orthogonal experiments including adsorption time, integrated probe dosage and solution pH, there was a good linear relationship between the peak current and Pb concentration ranging from 2.0 × 10 μg L to 2.0 × 10 μg L, with the limit of detection (LOD) being 6.7 × 10 μg L (S/N = 3) i.e. 0.067 ppt. Analysis of actual water samples was successful. Therefore, being simple, fast, selective and sensitive, the one-step electrochemical sensor proposed has a good potential in practical applications.
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http://dx.doi.org/10.1016/j.aca.2020.07.007DOI Listing
September 2020

Lycorine attenuates lipopolysaccharide-induced acute lung injury through the HMGB1/TLRs/NF-κB pathway.

3 Biotech 2020 Aug 1;10(8):369. Epub 2020 Aug 1.

Department of ICU, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin, 150001 Heilongjiang People's Republic of China.

Lung injury associated with systemic inflammatory response is a common problem affecting human health. Previous studies have shown that lycorine exerts a anti-inflammatory effect. However, whether lycorine alleviates lung injury remains unclear. To explore this issue, BALB/c mice and MLE-12 cells were treated with lipopolysaccharide (LPS) to establish lung injury mouse model and cell model, respectively. Glycyrrhizic acid, known as an inhibitor of ALI, was also used to study the effects of lycorine in vitro. Our results showed that after LPS treatment, the lung injury score, lung wet-to-dry weight ratio, and malondialdehyde (MDA) production in the lung tissues and the expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid were significantly increased, whereas their levels were decreased by lycorine. Additionally, LPS injection activated the high-mobility group box 1 (HMGB1)/Toll-like receptors (TLRs)/NF-κB pathway. However, lycorine treatment attenuated the activity of the HMGB1/TLRs/NF-κB pathway in the lung tissues. In vitro studies showed that lycorine administration significantly decreased the levels of inflammatory cytokines and MDA and attenuated the activity of the HMGB1/TLRs/NF-κB pathway in LPS-treated cells. Moreover, the inhibitory effects of lycorine on the inflammatory response and oxidative stress in LPS-treated lung cells were similar with that of glycyrrhizic acid, and this inhibition was intensified by both lycorine and glycyrrhizic acid treatment. We suggest that lycorine could alleviate LPS-induced lung injury of inflammation and oxidative stress by blocking the HMGB1/TLRs/NF-κB pathway, which gives a new perspective for ALI therapy to treat lycorine as a potential treatment clinically.
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http://dx.doi.org/10.1007/s13205-020-02364-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395800PMC
August 2020

HNF4α regulates sulfur amino acid metabolism and confers sensitivity to methionine restriction in liver cancer.

Nat Commun 2020 08 7;11(1):3978. Epub 2020 Aug 7.

Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, 27709, USA.

Methionine restriction, a dietary regimen that protects against metabolic diseases and aging, represses cancer growth and improves cancer therapy. However, the response of different cancer cells to this nutritional manipulation is highly variable, and the molecular determinants of this heterogeneity remain poorly understood. Here we report that hepatocyte nuclear factor 4α (HNF4α) dictates the sensitivity of liver cancer to methionine restriction. We show that hepatic sulfur amino acid (SAA) metabolism is under transcriptional control of HNF4α. Knocking down HNF4α or SAA enzymes in HNF4α-positive epithelial liver cancer lines impairs SAA metabolism, increases resistance to methionine restriction or sorafenib, promotes epithelial-mesenchymal transition, and induces cell migration. Conversely, genetic or metabolic restoration of the transsulfuration pathway in SAA metabolism significantly alleviates the outcomes induced by HNF4α deficiency in liver cancer cells. Our study identifies HNF4α as a regulator of hepatic SAA metabolism that regulates the sensitivity of liver cancer to methionine restriction.
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http://dx.doi.org/10.1038/s41467-020-17818-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414133PMC
August 2020

FGF21 attenuates neurodegeneration through modulating neuroinflammation and oxidant-stress.

Biomed Pharmacother 2020 Sep 2;129:110439. Epub 2020 Jul 2.

Northeast Agricultural University, Harbin, China. Electronic address:

Previous studies indicate that FGF21 has ability to repair nerve injury, but the specific mechanism is less studied. The present study was designed to investigate the effects of FGF21 on neurodegeneration changes in aging and diabetic mice and its mechanism. The diabetic and aging mice were used to study the effects of FGF21 on neurodegeneration and possible mechanisms. These mice were administrated with PBS, FGF21 or metformin once daily for 4 or 6 months, then the mechanism was studied in SH-SY5Y cells. The relevant gene expression for neurodegeneration was assessed by Quantitative Real Time-PCR, Western blot, H&E staining, immunohistochemistry and ELISA. The Western blot results of NeuN showed that FGF21 inhibited the loss of neurons in diabetic and aging mice. H&E staining results showed that the karyopyknosis and tissue edema around dentate gyrus and Cornu Amonis 3 (CA3) area of hippocampus were also inhibited by FGF21 in aging and diabetes mice. In vivo results revealed that administration of FGF21 suppressed the aggregation of tau and β-amyloid in the brains of diabetic and aging mice. The aggregation resulted in apoptosis of neurons. Meanwhile, FGF21 significantly reduced the expression of Iba1, NF-κB, IL6 and IL8 (p < 0.05) and enhanced anti-oxidant enzymes (p < 0.05) in aging and diabetic mice. In addition, the phosphorylation of AKT and AMPKα were increased by FGF21 treatment. In vitro experiment showed that the aggregation of tau and β-amyloid wereincreased by LPS in SH-SY5Y cells, and FGF21 inhibited the aggregation through inhibiting the expression of NF-κB and promoting the phosphorylation of AKT and AMPKα. In conclusion, FGF21 attenuates neurodegeneration by reducing neuroinflammation and oxidant stress through regulating the NF-κB pathway and AMPKα/AKT pathway, which enhances the protective effect on mitochondria in neurons.
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http://dx.doi.org/10.1016/j.biopha.2020.110439DOI Listing
September 2020

Identification of Four Potential Biomarkers Associated With Coronary Artery Disease in Non-diabetic Patients by Gene Co-expression Network Analysis.

Front Genet 2020 24;11:542. Epub 2020 Jun 24.

Department of Cardiology, Affiliated Hospital of Weifang Medical University, Weifang, China.

Background: Coronary artery disease (CAD) is a type of cardiovascular disease that greatly hurts the health of human beings. Diabetic status is one of the largest clinical factors affecting CAD-associated gene expression changes. Most of the studies focus on diabetic patients, whereas few have been done for non-diabetic patients. Since the pathophysiological processes may vary among these patients, we cannot simply follow the standard based on the data from diabetic patients. Therefore, the prognostic and predictive diagnostic biomarkers for CAD in non-diabetic patient need to be fully recognized.

Materials And Methods: To screen out candidate genes associated with CAD in non-diabetic patients, weighted gene co-expression network analysis (WGCNA) was constructed to conduct an analysis of microarray expression profiling in patients with CAD. First, the microarray data GSE20680 and GSE20681 were downloaded from NCBI. We constructed co-expression modules WGCNA after excluding the diabetic patients. As a result, 18 co-expression modules were screened out, including 1,225 differentially expressed genes (DEGs) that were obtained from 152 patients (luminal stenosis ≥50% in at least one major vessel) and 170 patients (stenosis of <50%). Subsequently, a Pearson's correlation analysis was conducted between the modules and clinical traits. Then, a functional enrichment analysis was conducted, and we used gene network analysis to reveal hub genes. Last, we validated the hub genes with peripheral blood samples in an independent patient cohort using RT-qPCR.

Results: The results showed that the midnight blue module and the yellow module played vital roles in the pathogenesis of CAD in non-diabetic patients. Additionally, CD40, F11R, TNRC18, and calcium/calmodulin-dependent protein kinase type II gamma (CAMK2G) were screened out and validated using enzyme-linked immunosorbent assay (ELISA) in an independent patient cohort and immunohistochemical (IHC) staining in an atherosclerosis mouse model.

Conclusion: Our findings demonstrate that hub genes, CD40, F11R, TNRC18, and CAMK2G, are surrogate diagnostic biomarkers and/or therapeutic targets for CAD in non-diabetic patients and require deeper validation.
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http://dx.doi.org/10.3389/fgene.2020.00542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344232PMC
June 2020

Sulfonate Versus Sulfonate: Nickel and Palladium Multimetallic Cross-Electrophile Coupling of Aryl Triflates with Aryl Tosylates.

J Am Chem Soc 2020 06 8;142(24):10634-10640. Epub 2020 Jun 8.

University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.

While phenols are frequent and convenient aryl sources in cross-coupling, typically as sulfonate esters, the direct cross-Ullmann coupling of two different sulfonate esters is unknown. We report here a general solution to this challenge catalyzed by a combination of Ni and Pd with Zn reductant and LiBr as an additive. The reaction has broad scope, as demonstrated in 33 examples (65% ± 11% average yield). Mechanistic studies show that Pd strongly prefers the aryl triflate, the Ni catalyst has a small preference for the aryl tosylate, aryl transfer between catalysts is mediated by Zn, and Pd improves yields by consuming arylzinc intermediates.
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http://dx.doi.org/10.1021/jacs.0c04670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373434PMC
June 2020

Cytokine Levels in the Body Fluids of a Patient With COVID-19 and Acute Respiratory Distress Syndrome: A Case Report.

Ann Intern Med 2020 09 12;173(6):499-501. Epub 2020 May 12.

The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China (K.K., M.Z., K.Y.).

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http://dx.doi.org/10.7326/L20-0354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224607PMC
September 2020

Efficacy and Safety of Lamivudine or Telbivudine in Preventing Mother-to-Child Transmission of Hepatitis B Virus: A Real-World Study.

Biomed Res Int 2020 27;2020:1374276. Epub 2020 Apr 27.

Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Background: There are few large sample studies evaluating the safety and efficacy of lamivudine (LAM) or telbivudine (LdT) in preventing hepatitis B mother-to-child transmission (MTCT) in highly viremic mothers in the third trimester of pregnancy in real-world settings. The purpose of this study was to analyze a large sample size of HBV-infected mothers to better understand the safety and efficacy of LAM and LdT under the aforementioned criteria.

Methods: During the period of November 2008 to November 2017, we retrospectively enrolled mothers with HBV DNA > 1 × 10 IU/mL who received LAM or LdT during the third trimester of pregnancy and compared them to untreated mothers. All mothers were divided into the three following groups: the LAM group, the LdT group, and the control group.

Results: A total of 2624 HBV-infected mothers were enrolled in the study, with 363 in the LAM group, 1283 in the LdT group, and 978 in the control group. The MTCT rates were significantly lower in the LAM or LdT group than that in the control group (0.4% or 0.3% versus 9.0%, < 0.001). Infants born to untreated mothers had a significantly higher risk of HBV infection (OR = 28.6, 95% CI: 10.4-78.7, < 0.001). There were no significant differences in perinatal complications between the three groups ( > 0.05). There were also no differences for gestational age or infants' height, weight, Apgar scores, or birth defect rates. Postpartum discontinuation of antiviral therapy did not seem to increase the risk of postpartum alanine aminotransferase (ALT) flare.

Conclusion: LAM or LdT treatment initiated in the third trimester for mothers with HBV DNA > 1 × 10 IU/mL was equally safe and effective in preventing MTCT.
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http://dx.doi.org/10.1155/2020/1374276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201734PMC
February 2021