Publications by authors named "Hua Lu"

699 Publications

Pdcd10-Stk24/25 complex controls kidney water reabsorption by regulating Aqp2 membrane targeting.

JCI Insight 2021 Jun 22;6(12). Epub 2021 Jun 22.

Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, China.

PDCD10, also known as CCM3, is a gene found to be associated with the human disease cerebral cavernous malformations (CCMs). PDCD10 forms a complex with GCKIII kinases including STK24, STK25, and MST4. Studies in C. elegans and Drosophila have shown a pivotal role of the PDCD10-GCKIII complex in maintaining epithelial integrity. Here, we found that mice deficient of Pdcd10 or Stk24/25 in the kidney tubules developed polyuria and displayed increased water consumption. Although the expression levels of aquaporin genes were not decreased, the levels of total and phosphorylated aquaporin 2 (Aqp2) protein in the apical membrane of tubular epithelial cells were decreased in Pdcd10- and Stk24/25-deficient mice. This loss of Aqp2 was associated with increased expression and membrane targeting of Ezrin and phosphorylated Ezrin, Radixin, Moesin (p-ERM) proteins and impaired intracellular vesicle trafficking. Treatment with Erlotinib, a tyrosine kinase inhibitor promoting exocytosis and inhibiting endocytosis, normalized the expression level and membrane abundance of Aqp2 protein, and partially rescued the water reabsorption defect observed in the Pdcd10-deficient mice. Our current study identified the PDCD10-STK-ERM signaling pathway as a potentially novel pathway required for water balance control by regulating vesicle trafficking and protein abundance of AQP2 in the kidneys.
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http://dx.doi.org/10.1172/jci.insight.142838DOI Listing
June 2021

Valosin-containing protein stabilizes mutant p53 to promote pancreatic cancer growth.

Cancer Res 2021 Jun 7. Epub 2021 Jun 7.

Biochemistry and molecular biology, Tulane Univ. School of Medicine

Approximately 80% of human pancreatic ductal adenocarcinomas (PDAC) harbor TP53 mutations, among which R273H is the most frequent. Although p53-R273H is known to possess gain-of-function properties, how it is regulated in PDAC has not been extensively explored. Here we identify valosin-containing protein (VCP) as a regulator of p53-R273H by conducting immunoprecipitation (IP)-tandem mass spectrometry (LC-MS/MS) analysis. VCP bound p53-R273H at its DNA binding domain. Ectopic or endogenous VCP stabilized p53-R273H by binding to MDM2 and disrupting its association with mutant p53. Inhibition of VCP either by genetic depletion or the pharmacological inhibitor CB-5083 increased ubiquitination and degradation of p53-R273H, leading to cell death. Consistently, ablation of VCP markedly retarded growth of cultured PDAC cells and xenograft PDAC tumors. Together, these results unveil VCP as a novel partner of p53-R273H in promoting PDAC growth and as a potential target for developing anti-PDAC therapy.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3855DOI Listing
June 2021

Association Between Anticoagulation Outcomes and Venous Thromboembolism History in Chronic Thromboembolic Pulmonary Hypertension.

Front Cardiovasc Med 2021 21;8:628284. Epub 2021 May 21.

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

The association between anticoagulation outcomes and prior history of venous thromboembolism (VTE) in chronic thromboembolic pulmonary hypertension (CTEPH) has not been established. This study aimed to compare the efficacy and safety of anticoagulation treatment in CTEPH patients with and without prior history of VTE. A total of 333 CTEPH patients prescribed anticoagulants were retrospectively included from May 2013 to April 2019. The clinical characteristics were collected at their first admission. Incidental recurrent VTE and clinically relevant bleeding were recorded during follow-up. The Cox proportional regression models were used to identify potential factors associated with recurrent VTE and clinically relevant bleeding. Seventy patients (21%) without a prior history of VTE did not experience recurrent VTE during anticoagulation. Compared to CTEPH patients without a prior history of VTE, those with a prior history of VTE had an increased risk of recurrent VTE [2.27/100 person-year vs. 0/100 person-year; hazard ratio (HR), 8.92; 95% confidence interval (CI), 1.18-1142.00; = 0.029] but a similar risk of clinically relevant bleeding (3.90/100 person-year vs. 4.59/100 person-year; HR, 0.83; 95% CI, 0.38-1.78; = 0.623). Multivariate Cox analyses suggested that a prior history of VTE and interruption of anticoagulation treatments were significantly associated with an increased risk of recurrent VTE, while anemia and glucocorticoid use were significantly associated with a higher risk of clinically relevant bleeding. This study is the first to reveal that a prior history of VTE significantly increases the risk of recurrent VTE in CTEPH patients during anticoagulation treatment. This finding should be further evaluated in prospective studies.
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http://dx.doi.org/10.3389/fcvm.2021.628284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175786PMC
May 2021

Nanoparticle encapsulation of non-genotoxic p53 activator Inauhzin-C for improved therapeutic efficacy.

Theranostics 2021 12;11(14):7005-7017. Epub 2021 May 12.

Department of Biochemistry & Molecular Biology and Cancer Center, Tulane University School of Medicine, New Orleans, LA, USA.

The tumor suppressor protein p53 remains in a wild type but inactive form in ~50% of all human cancers. Thus, activating it becomes an attractive approach for targeted cancer therapies. In this regard, our lab has previously discovered a small molecule, Inauhzin (INZ), as a potent p53 activator with no genotoxicity. To improve its efficacy and bioavailability, here we employed nanoparticle encapsulation, making INZ-C, an analog of INZ, to nanoparticle-encapsulated INZ-C (n-INZ-C). This approach significantly improved p53 activation and inhibition of lung and colorectal cancer cell growth by n-INZ-C and while it displayed a minimal effect on normal human Wi38 and mouse MEF cells. The improved activity was further corroborated with the enhanced cellular uptake observed in cancer cells and minimal cellular uptake observed in normal cells. pharmacokinetic evaluation of these nanoparticles showed that the nanoparticle encapsulation prolongates the half-life of INZ-C from 2.5 h to 5 h in mice. These results demonstrate that we have established a nanoparticle system that could enhance the bioavailability and efficacy of INZ-C as a potential anti-cancer therapeutic.
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http://dx.doi.org/10.7150/thno.57404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171090PMC
May 2021

Prophylactic Intra-Arterial Injection of Lidocaine Prevents Trigeminocardiac Reflex During Endovascular Embolization for Dural Arteriovenous Fistula: A Report of 2 Cases.

Am J Case Rep 2021 Jun 2;22:e930837. Epub 2021 Jun 2.

Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu, China (mainland).

BACKGROUND Trigeminocardiac reflex (TCR) is a unique brain stem reflex that manifests as the sudden onset of hemodynamic perturbation in heart rate and blood pressure as a result of stimulation of any branches of the trigeminal nerve. Onyx™ embolization in cerebrovascular interventional surgery can trigger TCR, leading to severe hemodynamic fluctuations and even cardiac arrest. Appropriate prophylactic approaches to prevent Onyx™ embolization-induced TCR are still lacking. CASE REPORT We report the cases of 2 patients with recurrent and profound bradycardia due to TCR during endovascular Onyx™ embolization for a dural arteriovenous fistula. Prophylactic intra-arterial injection of lidocaine (10-20 mg) effectively and safely blocked the recurrence and potential occurrence of TCR. These 2 patients had reduced heart rate with either hypotension or hypertension during their TCR episodes, suggesting that stimulating a distinct cerebral artery (occipital artery versus vertebral artery branch) can initiate TCR by provoking the vagus nerve via the common neuronal pathway while simultaneously inhibiting or exciting the sympathetic pathway. CONCLUSIONS Intra-arterial injection of lidocaine during endovascular procedures can be recommended as an effective prophylactic approach for use in the treatment of the cerebrovascular disorder where there is high risk of embolization-induced TCR.
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http://dx.doi.org/10.12659/AJCR.930837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183304PMC
June 2021

Fabry-Perot cavity enhanced three-photon luminescence of atomically thin platinum diselenide.

Nanoscale 2021 May;13(19):9031-9038

Institute of Photonic Chips, University of Shanghai for Science and Technology, Shanghai 200093, China and Centre for Artificial-Intelligence Nanophotonics, School of Optical-Electrical and Computer Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.

Two-dimensional materials, such as transition metal dichalcogenides (TMDs), exhibit intriguing physical properties that lead to both fundamental research and technology development. The recently emerged platinum diselenide (PtSe2), as a new member of the TMDs, has attracted increasing attention because of its good air stability, large refractive index and high electron mobility. However, being atomically thin significantly hinders its interaction with light, severely limiting the spontaneous or stimulated linear and nonlinear emission. Particularly, its nonlinear up-converted emission has not been fully exploited yet. Here, we experimentally observed the distinct enhancement of nonlinear up-converted luminescence of CVD-grown PtSe2 atomic layers on a SiO2/Si substrate with the assistance of the Fabry-Perot cavity resonance. The laser irradiance dependent luminescence study reveals the three-photon process of this nonlinear emission for the first time. Compared with non-resonant excitation, the luminescence enhancement can be up to six times because of the optical interference induced local field enhancement at the excitation wavelength. Leveraging this three-photon luminescence, nonlinear optical imaging and encryption were demonstrated for exploring information security applications. These results will pave the way for integrating nonlinear optical devices with the PtSe2 2D material.
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http://dx.doi.org/10.1039/d1nr00348hDOI Listing
May 2021

Redox-Mediated Reversible Supramolecular Assemblies Driven by Switch and Interplay of Peptide Secondary Structures.

Biomacromolecules 2021 Jun 7;22(6):2563-2572. Epub 2021 May 7.

CAS Center of Excellence for Nanoscience, Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.

The construction of reversible supramolecular self-assembly remains a significant challenge. Here, we demonstrate the redox-triggered reversible supramolecular self-assembly governed by the "check and balance" of two secondary conformations within a brushlike peptide-selenopolypeptide conjugate. The conjugate constitutes a polypeptide backbone whose side chain contains selenoether functional moieties and double bonds to be readily grafted with β-sheet-prone short-peptide NapFFC. The backbone of the conjugate initially assumes a robust and rigid α-helical conformation, which inhibits the supramolecular assembly of the short peptide in the side chain and yields an overall irregular aggregate morphology under native/reduced conditions. Upon oxidation of the selenoether to more hydrophilic selenoxide, the backbone helix switches to a flexible and disordered conformation, which unleashes the side-chain NapFFC self-assembly into nanofibrils via the adoption of β-sheet conformation. The reversible switch of the supramolecular morphology enables efficient loading and tumor-microenvironment-triggered release of anticancer drugs for cancer treatment with satisfactory efficacy and biocompatibility. The interplay and interaction between two well-defined secondary structures within one scaffold offer tremendous opportunity for the design and construction of functional supramolecular biomaterials.
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http://dx.doi.org/10.1021/acs.biomac.1c00300DOI Listing
June 2021

The association between extreme temperature and pulmonary tuberculosis in Shandong Province, China, 2005-2016: a mixed method evaluation.

BMC Infect Dis 2021 May 1;21(1):402. Epub 2021 May 1.

Department of Epidemiology, School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, No.619 Changcheng Road, Taian, 271016, Shandong Province, China.

Background: The effects of extreme temperature on infectious diseases are complex and far-reaching. There are few studies to access the relationship of pulmonary tuberculosis (PTB) with extreme temperature. The study aimed to identify whether there was association between extreme temperature and the reported morbidity of PTB in Shandong Province, China, from 2005 to 2016.

Methods: A generalized additive model (GAM) was firstly conducted to evaluate the relationship between daily reported incidence rate of PTB and extreme temperature events in the prefecture-level cities. Then, the effect estimates were pooled using meta-analysis at the provincial level. The fixed-effect model or random-effect model was selected based on the result of heterogeneity test.

Results: Among the 446,016 PTB reported cases, the majority of reported cases occurred in spring. The higher reported incidence rate areas were located in Liaocheng, Taian, Linyi and Heze. Extreme low temperature had an impact on the reported incidence of PTB in only one prefecture-level city, i.e., Binzhou (RR = 0.903, 95% CI: 0.817-0.999). While, extreme high temperature was found to have a positive effect on reported morbidity of PTB in Binzhou (RR = 0.924, 95% CI: 0.856-0.997) and Weihai (RR = 0.910, 95% CI: 0.843-0.982). Meta-analysis showed that extreme high temperature was associated with a decreased risk of PTB (RR = 0.982, 95% CI: 0.966-0.998). However, extreme low temperature was no relationship with the reported incidence of PTB.

Conclusion: Our findings are suggested that extreme high temperature has significantly decreased the risk of PTB at the provincial levels. The findings have implications for developing strategies to response to climate change.
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http://dx.doi.org/10.1186/s12879-021-06116-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088045PMC
May 2021

Safety and Efficacy of Endovascular Therapy for Blood Blister-Like Aneurysms: Willis Covered Stents and Double Stents Assistant Coils-A Single Center Cohort Study.

Front Neurol 2021 8;12:606219. Epub 2021 Apr 8.

Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

To summarize and discuss the application of Willis covered stents (WCSs) and double stent-assisted coils in the treatment of blood blister-like aneurysms (BBAs). Thirty-two patients with BBAs treated from January 2015 to October 2020 were included in the study. Among them, 18 were treated using WCSs and 14 using double stents-assisted coils. The indications for treatment, perioperative findings, and postoperative follow-up results were collected and analyzed. All 32 patients had successful stent deployments. Complete aneurysm occlusion was achieved in all 18 patients treated with WCSs immediately. WCS-related adverse events included 2 cases of mild vasospasm and 4 aggressive procedure-related vasospasms during WCS deployment, a case of dissection after WCS deployment, and 1 death due to ipsilateral temporal lobe rebleeding at the sixth day after WCS deployment. In patients treated with double stent-assisted coils, there were 3 cases of neck remnants, 1 acute occlusion of the ipsilateral MCA branch, and 4 mild procedure-related intraoperative vasospasms. The mean follow-up period was 4.2±1.6 months (range 3-6 months). Follow-up imaging data were available for 25 patients (78.1%). In the first postoperative angiographic follow-up, all BBAs were completely occluded. Mild asymptomatic stent stenosis was observed in 3 patients treated with WCSs. Follow-up examination at 6 months after the employment of WCSs showed that the modified Rankin score (mRs) was 0 in 6 patients, 1 in 5 patients, 2 in 3 patients, 3 in 1 patient, 4 in 2 patients, and 6 in 1 patient. After treatment with double stents-assisted coils, the mRs was 0 in 4 patients, 1 in 5 patients, 2 in 3 patients, and 4 in 2 patients. WCSs and double stent-assisted coils for the treatment of BBAs are both safe and efficient. WCSs provide a higher rate of immediate occlusion; however, there was no significant difference in the long term.
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http://dx.doi.org/10.3389/fneur.2021.606219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060473PMC
April 2021

Observation of intermediates by online mass spectrometry to demonstrate the multiple mechanisms of dye-sensitized photocatalysis.

Chem Commun (Camb) 2021 Apr 23;57(32):3921-3924. Epub 2021 Mar 23.

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, P. R. China.

Online mass spectrometry was applied to reveal multiple mechanisms of visible-light irradiated dye-sensitized photocatalysis for o-phenylenediamine oxidation. The reactants, products and short-lived intermediates were recorded and dynamically tracked. Dimer and unexpected trimer intermediates were observed to deduce the stepwise aerobic photooxidation mechanism with multiple routes, which was supported by theoretical calculations.
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http://dx.doi.org/10.1039/d1cc00908gDOI Listing
April 2021

Pure erythroid leukemia subsequent to acute myelomonocytic leukemia: A case report.

Medicine (Baltimore) 2021 Apr;100(15):e25528

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Hematology of Nanjing Medical University.

Rationale: Pure erythroid leukemia is a rare subcategory of acute myeloid leukemia characterized by predominant immature erythroid population. Its occurrence subsequent to acute myelomonocytic leukemia has not been reported before. We reported this rare case to call attention because it may pose a diagnostic challenge.

Patients Concerns: A 54-year-old female patient presented to our hospital in March 2018 with symptoms of easy fatigability.

Diagnosis: Bone marrow aspiration was hypercellular showing 67.2% blasts mainly including moderate myeloblasts and monoblasts. There was mild dysplasia with some cells having round, oval, or bizarre nuclei which containing 1 to 3 nucleolus. Erythroid lineage was hypoplasia and mature erythrocytes were generally normal. Conventional cytogenetics of bone marrow cells revealed complex karyotype (44, XX, del (5) (q14q34) del (5) (q14q34), del (14) t (11;14) (q10; q10), -16, del (17), -18[10]).

Interventions: The patient was treated with second line chemotherapy but did not respond.

Qutcomes: She died of cardiopulmonary failure 19days after starting of therapy.

Lessons: This unexpected and relatively uncommon occurrence was associated with a universally rapid and fatal clinical course with survival measured in <2 months despite intensive chemotherapy. We call attention to this rare phenomenon because it may pose a diagnostic challenge.
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http://dx.doi.org/10.1097/MD.0000000000025528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052012PMC
April 2021

Comparison of the Simulated Response of Three Human Stem Cell-Derived Cardiomyocytes Models and Data Under 15 Drug Actions.

Front Pharmacol 2021 15;12:604713. Epub 2021 Mar 15.

Department of Computer Science, University of Oxford, Oxford, United Kingdom.

Improvements in human stem cell-derived cardiomyocyte (hSC-CM) technology have promoted their use for drug testing and disease investigations. Several hSC-CM models have been proposed to augment interpretation of experimental findings through simulations. This work aims to assess the response of three hSC-CM models (Koivumäki2018, Kernik2019, and Paci2020) to simulated drug action, and compare simulation results against data for 15 drugs. First, simulations were conducted considering 15 drugs, using a simple pore-block model and experimental data for seven ion channels. Similarities and differences were analyzed in the responses of the three models to drugs, in terms of Ca transient duration (CTD) and occurrence of arrhythmic events. Then, the sensitivity of each model to different degrees of blockage of Na (I), L-type Ca (I), and rapid delayed rectifying K (I) currents was quantified. Finally, we compared the drug-induced effects on CTD against the corresponding experiments. The observed CTD changes were overall consistent among the models, all three showing changes of smaller magnitudes compared to the ones measured . For example, sparfloxacin 10 µM induced +42% CTD prolongation , and +17% (Koivumäki2018), +6% (Kernik2019), and +9% (Paci2020) . Different arrhythmic events were observed following drug application, mainly for drugs affecting I. Paci2020 and Kernik2019 showed only repolarization failure, while Koivumäki2018 also displayed early and delayed afterdepolarizations. The spontaneous activity was suppressed by Na blockers and by drugs with similar effects on I and I in Koivumäki2018 and Paci2020, while only by strong I blockers, e.g. nisoldipine, in Kernik2019. These results were confirmed by the sensitivity analysis. To conclude, The CTD changes observed are qualitatively consistent with our data, although our simulations show differences in drug responses across the hSC-CM models, which could stem from variability in the experimental data used in their construction.
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http://dx.doi.org/10.3389/fphar.2021.604713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033762PMC
March 2021

Zichong granules promote differentiation of ovarian granulosa-like cells from human embryonic stem cells in vitro.

J Tradit Chin Med 2021 04;41(2):203-211

Department of Gynecology and Obstetrics, The Second Medical College/Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu 610041, China.

Objective: To investigate whether Zichong granules (, ZCKL), a very effective herbal formula for treating infertility, have an impact on the differentiation of ovarian granulosa cells from human embryonic stem cells (hESCs) in vitro, and to explore the cellular mechanisms of its clinical effects.

Methods: Serum from ZCKL-medicated rats was prepared and used to treat mesoderm cells derived from hESCs for 6 d. Normal rat serum and a set of growth factors were used as negative and positive controls, respectively.

Results: ZCKL-medicated rat serum, but not normal rat serum, induced hESCs-derived mesoderm cells to differentiate into functional ovarian granulosa-like cells (OGLCs) in a similar manner to defined growth factors. The induced OGLCs resembled the morphology of native human granulosa cells, expressed granulosa cell-specific markers at both the mRNA and protein levels, produced high levels of estradiol and strongly responded to follicle-stimulating hormone stimulation. Furthermore, mRNA levels of follistatin, mothers against decapentaplegic homolog 8 and bone morphogenetic protein 6 were dynamically changed during the process.

Conclusion: In the ZCKL treatment of infertility, one mechanism by which ZCKL may act is by influencing ovarian granulosa cell differentiation and development, possibly through the follistatin and BMP/SMAD signaling pathways.
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April 2021

Heron-mouth neuroendoscopic sheath-assisted neuroendoscopy plays critical roles in treating hypertensive intraventricular hemorrhage.

Wideochir Inne Tech Maloinwazyjne 2021 Mar 25;16(1):199-210. Epub 2020 Sep 25.

Department of Neurosurgery, Affiliated Hospital of Jiangnan University (Wuxi Third People's Hospital), Wuxi, China.

Introduction: Neuroendoscopy is widely applied for treating hypertensive intracerebral hemorrhage.

Aim: To explore the effects of heron-mouth neuroendoscopic sheath-assisted neuroendoscopy on treatment of hypertensive intraventricular hemorrhage.

Material And Methods: A type of heron-mouth neuroendoscopic sheath combining the advantages of minimally invasive columnar endoscopic sheath and open operation methods was designed. The end of sheath catheter could be dilated if necessary, without increasing risk of cortex injury. Heron-mouth neuroendoscopic sheath-assisted neuroendoscopy was applied in treatment of hypertensive intraventricular hemorrhage. A total of 19 patients with hypertensive intraventricular hemorrhage were selected and divided into an external ventricular drainage + urokinase group and a neuroendoscopy group. Hematoma clearance rate, surgical time, ventricular drainage time, intracranial infection, hydrocephalus and Glasgow Outcome Score (GOS) at 3 months after the operation were compared between two groups.

Results: Hematoma clearance rate, ventricular drainage time, mortality rate and GOS at 3 months after surgery in the neuroendoscopy group were significantly better compared to those in the external ventricular drainage + urokinase group (p < 0.05). Postoperative complications, including intracranial infection hydrocephalus and pulmonary infection in the neuroendoscopy group, were less numerous compared to those in the external ventricular drainage + urokinase group, but without statistical significance (p > 0.05). However, surgical time was significantly longer in the neuroendoscopy group compared to that in the external ventricular drainage + urokinase group (p < 0.05). There was no significant difference in incidence rate of hydrocephalus between the two groups (p > 0.05).

Conclusions: Clinical effects of heron-mouth neuroendoscopic sheath-assisted neuroendoscopy were better than those of external ventricular drainage combining urokinase dissolution in treating hypertensive intraventricular hemorrhage.
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http://dx.doi.org/10.5114/wiitm.2020.99351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991947PMC
March 2021

Potential Effects of the FLT3-ITD Mutation on Chemotherapy Response and Prognosis of Acute Promyelocytic Leukemia.

Cancer Manag Res 2021 12;13:2371-2378. Epub 2021 Mar 12.

Department of Haematology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu, People's Republic of China.

Purpose: To evaluate the influence of mutations on the treatment response and long-term survival of newly-diagnosed patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and arsenic trioxide.

Methods: The long-term survival of 90 newly-diagnosed APL patients (age range 12-75 years) was retrospectively analyzed.The mutation rate was assayed by polymerase chain reaction (PCR) amplification and sequencing analysis. Its impact on the treatment response, event-free survival(EFS), or overall survival(OS) was investigated in patients with and without the mutations.

Results: The mutation rate in newly-diagnosed APL patients was 20% (18/90). The white blood cell (WBC) count at diagnosis in patients with mutations was significantly higher than that in patients without mutations while the mutation rate was higher in the high-risk group than in the low/intermediate-risk group. Patients with mutations had a significantly higher early death (ED) rate (16.67% vs 1.39%) for those lacking the mutation ( =0.024). However, the complete remission (CR) and differentiation syndrome (DS) rates in the two groups were similar. Kaplan Meier analysis for EFS and OS at five years showed a significant difference between the patients stratified by mutation status (log-rank =0.010 and =0.009, respectively).

Conclusion: mutations can be related to high peripheral WBC counts in APL patients. APL patients with mutations displayed a higher ED rate compared to those without mutations. Patients carrying mutations had reduced five-year EFS and OS rates. Thus, reducing the overall death rate during induction treatment might be an effective way to improve the prognosis of patients with mutations.
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http://dx.doi.org/10.2147/CMAR.S297421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965687PMC
March 2021

Adaptation of a marine diatom to ocean acidification and warming reveals constraints and trade-offs.

Sci Total Environ 2021 Jun 29;771:145167. Epub 2021 Jan 29.

School of Environmental Science and Engineering, Guangzhou University, Guangzhou 510006, China.

Ocean acidification and warming are recognized as two major anthropogenic perturbations of the modern ocean. However, little is known about the adaptive response of phytoplankton to them. Here we examine the adaptation of a marine diatom Thalassiosira weissflogii to ocean acidification in combination with ocean warming. Our results show that ocean warming have a greater effect than acidification on the growth of T. weissflogii over the long-term selection experiment (~380 generations), as well as many temperature response traits (e.g., optimum temperatures for photosynthesis, maximal net photosynthetic oxygen evolution rates, activation energy) in thermal reaction norm. These results suggest that ocean warming is the main driver for the evolution of the marine diatom T. weissflogii, rather than oceanacidification. However, the evolution resulting from warming can be constrained by ocean acidification, where ocean warming did not impose any effects at high CO level. Furthermore, adaptations to ocean warming alone or to the combination of ocean acidification and warming come with trade-offs by inhibiting photochemical performances. The constrains and trade-offs associated with the adaptation to ocean acidification and warming demonstrated in this study, should be considered for parameterizing evolutionary responses in eco-evolutionary models of phytoplankton dynamics in a future ocean.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145167DOI Listing
June 2021

The impact of COVID-19 on sexual behaviors of young women and men: A protocol for systematic review and meta analysis.

Medicine (Baltimore) 2021 Feb;100(8):e24415

Maternal and Child Reproductive Hospital affiliated to Chengdu University of Traditional Chinese Medicine, NO.17, Section 4, South Renmin Road, Chengdu, Sichuan Province, PR China.

Background: The worldwide impact of COVID-19 has reached all spheres of human health. Individuals may also experience unique changes in their sexual behaviors during the COVID-19 self-isolation/social distancing period. Studies in many countries have assess the effects of the pandemic on sexual behavior, or quality of sexual life. However, no systematic review has comprehensively explored the association between COVID-19 and the sexual behaviors of young women and men to date. This systematic review and meta-analysis protocol aims to ascertain the association between COVID-19 and sexual behaviors of young women and men that may get targeted interventions to improve health and well-being of young people's sexual health.

Methods: This systematic review and meta-analysis will be reported following the PRISMA guidelines. Observational designs (including cross-sectional, case-control, and cohort) will be eligible. Studies eligible for inclusion must contain participants aged 15 to 45 in any country affected by the pandemic of COVID-19. The search will be conducted in the following databases, including PubMed, Cochrane Library, EMBASE, EBSCO, Ovid, WHO COVID-19 database, China National Knowledge Internet (CNKI), WanFang Data, Chinese Scientific and Technological Journal Database (VIP), and Chinese Biomedical Databases (CBM). A pre-designed search strategy of medical subject heading (MeSH) terms and free words for the concepts "COVID-19" and "sexual behaviors" will be used. Two authors will independently complete literature screening, data extraction, and risk of bias assessment. Disagreements will be resolved by consensus with a third reviewer. The reviewer will follow the PECOS steps (population, exposure, comparator, outcomes, and study design) to obtain eligible extraction items. The risk of bias and quality of included studies will be assessed using RevMan 5.3. We will assess heterogeneity according to the I2 statistics. If there is substantial heterogeneity in the included trials, subgroup analysis will be carried out to seek the potential causes.

Ethics And Dissemination: It is not necessary to obtain ethical approval as we will use data from published articles. The findings of this systematic review will be published in a peer- reviewed journal.

Prospero Registration Number: PROSPERO 2020: CRD42020190867.
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http://dx.doi.org/10.1097/MD.0000000000024415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909130PMC
February 2021

Impact of pre-transplantation minimal residual disease (MRD) on the outcome of Allogeneic hematopoietic stem cell transplantation for acute leukemia.

Hematology 2021 Dec;26(1):295-300

Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, People's Republic of China.

Objective: To investigate the impact of minimal residual disease (MRD) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the outcome of acute leukemia.

Methods: Data from 114 patients who were diagnosed with acute leukemia (AL) and underwent allo-HSCT between Jan 2013 and Dec 2019 were collected and analyzed. The patients were attributed into MRD positive (MRD+) group and MRD negative (MRD-) group.

Results: Among the 114 acute leukemia patients, there were 32 MRD+ patients before transplantation, and 82 MRD- patients. No significant difference was found between the MRD+ group and the MRD- group in the incidence of acute graft-versus-host disease (aGvHD)  = 0.09). Compared with the MRD+ group, the MRD- group had a higher incidence of chronic graft-versus-host disease (cGvHD) ( = 0.008). There is no significance in relapse between the two groups ( = 0.084), while the incidence of relapse was seemingly higher in the MRD+ group: 36.9% Vs 19.7% . We attributed to the lack of sample size and NRM in MRD+ group was remarkably higher. The MRD+ group had significantly worse one-year overall survival (OS) ( ,  = 0.003) and one-year progression-free survival (PFS) (,  = 0.009). In the multivariate analysis, MRD+ was an independent prognostic factor for OS (HR = 1.898; 95%CI 1.042-3.457;  = 0.036).

Conclusion: Pre-transplantation MRD positive status is a risk factor for survival and prognosis after HSCT. Upon this, emphasis should be put on (1) screening more efficient chemo regimen with targeted agents, to help patients reach and keep MRD- status before transplantation; (2) designing better management with different GvHD prophylaxis treatment, timely disease monitoring and preemptive intervention on relapse.
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http://dx.doi.org/10.1080/16078454.2021.1889162DOI Listing
December 2021

Impact of COVID-19 on female fertility: a systematic review and meta-analysis protocol.

BMJ Open 2021 02 25;11(2):e045524. Epub 2021 Feb 25.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Introduction: The increased social and economic burden caused by the novel COVID-19 outbreak is gradually becoming a worrisome issue for the health sector. The novel coronavirus invades the target cell by binding to ACE2, which is widely expressed in the ovaries, uterus, vagina and placenta. Significantly, the SARS-CoV-2 is said to interrupt female fertility through regulating ACE2. Thus, it is essential to investigate if the novel COVID-19 hampers female fertility, given that there is no systematic and comprehensive evidence on the association of COVID-19 with female fertility.

Methods And Analysis: We will systematically search cohort studies, cross-sectional studies, case-control studies and self-controlled case series designs in the following databases: Web of Science, PubMed, EMBASE, Cochrane Library, Ovid, EBSCO, WHO COVID-19 Database, Chinese Biomedical Databases, China National Knowledge Internet, VIP and WanFang Database. Medical Subject Headings and free-text terms for "COVID-19" AND "female" AND "fertility" will be performed. Eligibility criteria are as follows: population (female patients aged 13-49 years); exposure (infection with SARS-CoV-2); comparison (population without SARS-CoV-2 infections or latent SARS-CoV-2 infections); and outcome (female fertility, such as ovarian reserve function, uterine receptivity, oviducts status and menstruation status). Article screening and data extraction will be undertaken independently by two reviewers, and discrepancies will be resolved through discussion. We will use the I statistics to assess the heterogeneity and perform a meta-analysis when sufficiently homogeneous studies are provided. Otherwise, a narrative synthesis will be performed. We will explore the potential sources of heterogeneity using subgroup analyses and meta-regression.

Ethics And Dissemination: Formal ethical approval is not required, and findings will be published in a peer-reviewed journal.

Prospero Registration Number: CRD42020189856.
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http://dx.doi.org/10.1136/bmjopen-2020-045524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908052PMC
February 2021

p53 induces ARTS to promote mitochondrial apoptosis.

Cell Death Dis 2021 02 24;12(2):204. Epub 2021 Feb 24.

Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.

Apoptosis related protein in TGF-β signaling pathway (ARTS) was originally discovered in cells undergoing apoptosis in response to TGF-β, but ARTS also acts downstream of many other apoptotic stimuli. ARTS induces apoptosis by antagonizing the anti-apoptotic proteins XIAP and Bcl-2. Here we identified the pro-apoptotic Sept4/ARTS gene as a p53-responsive target gene. Ectopic p53 and a variety of p53-inducing agents increased both mRNA and protein levels of ARTS, whereas ablation of p53 reduced ARTS expression in response to multiple stress conditions. Also, γ-irradiation induced p53-dependent ARTS expression in mice. Consistently, p53 binds to the responsive DNA element on the ARTS promoter and transcriptionally activated the promoter-driven expression of a luciferase reporter gene. Interestingly, ARTS binds to and sequesters p53 at mitochondria, enhancing the interaction of the latter with Bcl-XL. Ectopic ARTS markedly augments DNA damage stress- or Nutlin-3-triggered apoptosis, while ablation of ARTS preferentially impairs p53-induced apoptosis. Altogether, these findings demonstrate that ARTS collaborates with p53 in mitochondria-engaged apoptosis.
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http://dx.doi.org/10.1038/s41419-021-03463-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904775PMC
February 2021

Positive feedback of SuFu negating protein 1 on Hedgehog signaling promotes colorectal tumor growth.

Cell Death Dis 2021 02 19;12(2):199. Epub 2021 Feb 19.

Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 330006, Nanchang, Jiangxi, China.

Hedgehog (Hh) signaling plays a critical role in embryogenesis and tissue homeostasis, and its deregulation has been associated with tumor growth. The tumor suppressor SuFu inhibits Hh signaling by preventing the nuclear translocation of Gli and suppressing cell proliferation. Regulation of SuFu activity and stability is key to controlling Hh signaling. Here, we unveil SuFu Negating Protein 1 (SNEP1) as a novel Hh target, that enhances the ubiquitination and proteasomal degradation of SuFu and thus promotes Hh signaling. We further show that the E3 ubiquitin ligase LNX1 plays a critical role in the SNEP1-mediated degradation of SuFu. Accordingly, SNEP1 promotes colorectal cancer (CRC) cell proliferation and tumor growth. High levels of SNEP1 are detected in CRC tissues and are well correlated with poor prognosis in CRC patients. Moreover, SNEP1 overexpression reduces sensitivity to anti-Hh inhibitor in CRC cells. Altogether, our findings demonstrate that SNEP1 acts as a novel feedback regulator of Hh signaling by destabilizing SuFu and promoting tumor growth and anti-Hh resistance.
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http://dx.doi.org/10.1038/s41419-021-03487-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896051PMC
February 2021

Effect of Kangfuxin Liquid enema combined with mesalazine on gestational outcomes and quality of life in child-bearing female with active ulcerative colitis: A protocol for randomized, double-blind, controlled trial.

Medicine (Baltimore) 2021 Feb;100(5):e23915

College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine.

Background: In recent years, the incidence of ulcerative colitis (UC) is on the rise, and most of them are young adults. As the peak of the disease overlaps with the childbearing age, it has a great impact on the fertility of female patients. We, therefore, conduct a randomized and controlled trial to evaluate the efficacy and safety of mesalazine enteric-coated tablets combined with Kangfuxin Liquid (KFX) enema for the child-bearing period female with active UC.

Methods: In this randomized controlled study, a total of 236 eligible patients will be assigned to the experimental group (n = 118) or the control group (n = 118) in a 1:1 ratio. The control group will be taken mesalazine enteric-coated tablets combined with placebo enema and the experimental group will be taken mesalazine enteric-coated tablets combined with KFX enema. Participants will receive 8 weeks of intervention treatment and 3 months of maintenance treatment before pregnancy. The primary assessment is the Mayo score. Secondary outcomes include mucosal healing, faecal calprotectin (FC), Inflammatory Bowel Disease Quality (IBDQ), and pregnancy outcome.

Discussion: This study will provide evidence regarding the efficacy and safety of KFX enema used before pregnancy on halting active UC, reducing the relapse rate during pregnancy, improving pregnancy outcome, and the quality of life.

Trial Registration: Chinese Clinical Trials Register identifier, ChiCTR2000039161, registered on October 20, 2020.
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http://dx.doi.org/10.1097/MD.0000000000023915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870172PMC
February 2021

Early therapeutic interventions of traditional Chinese medicine in COVID-19 patients: A retrospective cohort study.

J Integr Med 2021 05 13;19(3):226-231. Epub 2021 Jan 13.

Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.

Objective: To observe the early interventions of traditional Chinese Medicine (TCM) on the conversion time of nucleic acid in patients with coronavirus disease 2019 (COVID-19), and find possible underlying mechanisms of action.

Methods: A retrospective cohort study was conducted on 300 confirmed COVID-19 patients who were treated with TCM, at a designated hospital in China. The patients were categorized into three groups: TCM1, TCM2 and TCM3, who respectively received TCM interventions within 7, 8-14, and greater than 15 days of hospitalization. Different indicators such as the conversion time of pharyngeal swab nucleic acid, the conversion time of fecal nucleic acid, length of hospital stay, and inflammatory markers (leukocyte count, and lymphocyte count and percentage) were analyzed to observe the impact of early TCM interventions on these groups.

Results: The median conversion times of pharyngeal swab nucleic acid in the three groups were 5.5, 7 and 16 d (P < 0.001), with TCM1 and TCM2 being statistically different from TCM3 (P < 0.01). TCM1 (P < 0.05) and TCM3 (P < 0.01) were statistically different from TCM2. The median conversion times of fecal nucleic acid in the three groups were 7, 9 and 17 d (P < 0.001). Conversion times of fecal nucleic acid in TCM1 were statistically different from TCM3 and TCM2 (P < 0.01). The median lengths of hospital stay in the three groups were 13, 16 and 21 d (P < 0.001). TCM1 and TCM2 were statistically different from TCM3 (P < 0.01); TCM1 and TCM3 were statistically different from TCM2 (P < 0.01). Both leucocyte and lymphocyte counts increased gradually with an increase in the length of hospital stay in TCM1 group patients, with a statistically significant difference observed at each time point in the group (P < 0.001). Statistically significant differences in lymphocyte count and percentage in TCM2 (P < 0.001), and in leucocyte count (P = 0.043) and lymphocyte count (P = 0.038) in TCM3 were observed. The comparison among the three groups showed a statistically significant difference in lymphocyte percentage on the third day of admission (P = 0.044).

Conclusion: In this study, it was observed that in COVID-19 patients treated with a combination of Chinese and Western medicines, TCM intervention earlier in the hospital stay correlated with faster conversion time of pharyngeal swab and fecal nucleic acid, as well as shorter length of hospital stay, thus helping promote faster recovery of the patient. The underlying mechanism of action may be related to improving inflammation in patients with COVID-19.
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http://dx.doi.org/10.1016/j.joim.2021.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832636PMC
May 2021

Rare variants in MTHFR predispose to occurrence and recurrence of pulmonary embolism.

Int J Cardiol 2021 05 8;331:236-242. Epub 2021 Feb 8.

Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing 100037, China. Electronic address:

Background: Rare genetic variants play a critical role in unprovoked pulmonary embolism (PE). However, the known risk genes only account a small proportion of patients with PE. The objective of this study was to investigate the relationship between the rare variants of gene encoding methylenetetrahydrofolate reductase (MTHFR) and the initiation and long-term clinical outcomes of PE.

Methods: The rare variants of MTHFR were detected by whole exome sequencing of DNA from 258 unprovoked PE cases and 11,451 controls. Correlation of genotype and clinical phenotype and outcome were evaluated at baseline and after follow-up.

Results: MTHFR rare variants were found in 15 of 258 cases (5.81%) and 241 of 11,451 controls (2.10%), conferring 2.87-fold greater odds of the PE occurrence (OR = 2.87, 95% CI = 1.68-4.91, P = 5.6 × 10, chi-square test). The patients with MTHFR rare variants had higher plasma level of homocysteine than those without. During a follow-up of 3.0 years, a total of 84 events were identified. The recurrent PE (two or more events of PE) were significantly higher in patients carrying MTHFR rare variants (8/15, 53.3%) compared with those without (55/239, 23.0%) (P = 0.023).

Conclusion: We speculate that MTHFR rare variants may increase the occurrence and recurrence of PE.
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http://dx.doi.org/10.1016/j.ijcard.2021.01.073DOI Listing
May 2021

Effect of Mechanical Strain on Cells Involved in Fracture Healing.

Orthop Surg 2021 Apr 25;13(2):369-375. Epub 2021 Jan 25.

Department of Orthopaedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Secondary fracture healing is a complex multi-stage process in which the mechanical environment plays a key role. The use of an appropriate mechanical stimulation such as strain is conducive to tissue formation between fracture ends, thus aiding the healing process. However, if the strain is too large or too small, the biological behavior of the cells involved in bone healing will be affected, resulting in non-union or delayed healing. In this review, we summarize the current state of knowledge regarding the effect of strain on cells that play a role in the fracture-healing process. Overall, the related literature suggests that selection of an adequate strain promotes fracture healing through the stimulation of angiogenesis and osteogenesis, along with inhibition of osteoclast differentiation and bone resorption. However, standardized methods for the application of mechanical stimulation are lacking, and a unified consensus on the mechanism by which strain promotes cell differentiation has not yet been reached. These issues, therefore, deserve further investigation.
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http://dx.doi.org/10.1111/os.12885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957396PMC
April 2021

Effectiveness of electroacupuncture for thin endometrium in infertile women: study protocol for a single-blind, randomized controlled trial.

Trials 2021 Jan 21;22(1):73. Epub 2021 Jan 21.

College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, NO.37 Shi-er-qiao Road, Chengdu, 610075, Sichuan Province, People's Republic of China.

Background: Thin endometrium negatively impacts the reproductive function. Current treatments for thin endometrium do not always improve endometrial receptivity. Preliminary evidence suggests that electroacupuncture could have potential therapy for thin endometrium in infertile women. Thus, this randomized controlled trial was designed to test whether electroacupuncture can improve endometrial receptivity in infertile women with thin endometrium.

Methods: This study is a randomized, single-blinded, controlled, clinical trial. A total of 142 eligible patients will be recruited and randomly assigned to the electroacupuncture (EA) group or the sham electroacupuncture (SEA) group in a 1:1 ratio. Participants will receive 36 sessions over three menstrual cycles (12 weeks in total), with the same acupoint prescription. The primary outcome of this trial is endometrial thickness in the midluteal phase. The secondary outcomes include endometrial pattern, resistance index (RI) and pulsatility index (PI) of bilateral uterine artery and endometrium blood flow, serum estradiol (E2) and progesterone (P), and pregnancy rate. The pregnancy rate will be evaluated during a 6-month follow-up after completion of the trial. All other outcomes will be evaluated before treatment, during the treatment of 1st, 2nd, and 3rd menstrual cycle, and 6 months after treatment.

Discussion: If the outcome confirms the effectiveness of electroacupuncture for thin endometrium in infertile women, this treatment will be proposed for application in clinical practice.

Trial Registration: Chinese Clinical Trials Registry ChiCTR2 000029983. Registered on 18 February 2020.
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http://dx.doi.org/10.1186/s13063-021-05029-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818916PMC
January 2021

Numerical modeling in arterial hemodynamics incorporating fluid-structure interaction and microcirculation.

Theor Biol Med Model 2021 01 19;18(1). Epub 2021 Jan 19.

Thrombosis Center, National Clinical Research Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.

Background: The effects of arterial wall compliance on blood flow have been revealed using fluid-structure interaction in last decades. However, microcirculation is not considered in previous researches. In fact, microcirculation plays a key role in regulating blood flow. Therefore, it is very necessary to involve microcirculation in arterial hemodynamics.

Objective: The main purpose of the present study is to investigate how wall compliance affects the flow characteristics and to establish the comparisons of these flow variables with rigid wall when microcirculation is considered.

Methods: We present numerical modeling in arterial hemodynamics incorporating fluid-structure interaction and microcirculation. A novel outlet boundary condition is employed to prescribe microcirculation in an idealised model.

Results: The novel finding in this work is that wall compliance under the consideration of microcirculation leads to the increase of wall shear stress in contrast to rigid wall, contrary to the traditional result that wall compliance makes wall shear stress decrease when a constant or time dependent pressure is specified at an outlet.

Conclusions: This work provides the valuable study of hemodynamics under physiological and realistic boundary conditions and proves that wall compliance may have a positive impact on wall shear stress based on this model. This methodology in this paper could be used in real model simulations.
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http://dx.doi.org/10.1186/s12976-021-00136-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816504PMC
January 2021

The resting membrane potential of hSC-CM in a syncytium is more hyperpolarised than that of isolated cells.

Channels (Austin) 2021 Dec;15(1):239-252

Department of Biomedical Sciences, University of Antwerp , Antwerp, Belgium.

Human-induced pluripotent stem cell (hiPSC) and stem cell (hSC) derived cardiomyocytes (CM) are gaining popularity as in vitro model for cardiology and pharmacology studies. A remaining flaw of these cells, as shown by single-cell electrophysiological characterization, is a more depolarized resting membrane potential (RMP) compared to native CM. Most reports attribute this to a lower expression of the Kir2.1 potassium channel that generates the I current. However, most RMP recordings are obtained from isolated hSC/hiPSC-CMs whereas in a more native setting these cells are interconnected with neighboring cells by connexin-based gap junctions, forming a syncytium. Hereby, these cells are electrically connected and the total pool of I increases. Therefore, the input resistance (Ri) of interconnected cells is lower than that of isolated cells. During patch clamp experiments pipettes need to be well attached or sealed to the cell, which is reflected in the seal resistance (Rs), because a nonspecific ionic current can leak through this pipette-cell contact or seal and balance out small currents within the cell such as I. By recording the action potential of isolated hSC-CMs and that of hSC-CMs cultured in small monolayers, we show that the RMP of hSC-CMs in monolayer is approximately -20 mV more hyperpolarized compared to isolated cells. Accordingly, adding carbenoxolone, a connexin channel blocker, isolates the cell that is patch clamped from its neighboring cells of the monolayer and depolarizes the RMP. The presented data show that the recorded RMP of hSC-CMs in a syncytium is more negative than that determined from isolated hSC/hiPSC-CMs, most likely because the active pool of Kir2.1 channels increased.
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http://dx.doi.org/10.1080/19336950.2021.1871815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817136PMC
December 2021

Thrombus straddling a patent foramen ovale in a patient with pulmonary embolism related to essential thrombocythemia.

Int J Hematol 2021 Feb 2;113(2):159-160. Epub 2021 Jan 2.

Thrombosis Center, Key Laboratory of Pulmonary Vascular Medicine, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.

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http://dx.doi.org/10.1007/s12185-020-03033-2DOI Listing
February 2021