Publications by authors named "Juan He"

365 Publications

CoFeO-Quantum Dots for Synergistic Photothermal/Photodynamic Therapy of Non-small-Cell Lung Cancer Via Triggering Apoptosis by Regulating PI3K/AKT Pathway.

Nanoscale Res Lett 2021 Jul 28;16(1):120. Epub 2021 Jul 28.

Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, Guangdong, China.

Non-small-cell lung cancer (NSCLC) has become the second most diagnosed malignant tumors worldwide. As our long-term interests in seeking nanomaterials to develop strategies of cancer therapies, we herein constructed novel CoFeO-quantum dots (QDs) with outstanding synergistic photothermal/photodynamic property which suppressed NSCLC efficiently without apparent toxicity. We showed that the combination of CoFeO-QDs + NIR treatment induces apoptosis of NSCLC cells. In addition, the CoFeO-QDs + NIR treatment also promotes reactive oxygen species generation to trigger cell death through regulating PI3K/AKT pathway. Moreover, the CoFeO-QDs + NIR treatment successfully eliminates tumor xenografts in vivo without apparent toxic effects. Taken together, we reported that the novel nanomaterials CoFeO-QDs could exhibit enhanced synergistic photothermal therapy and photodynamic therapy effect on killing NSCLC without toxicity, which could be a promising photosensitizer for NSCLC therapy.
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http://dx.doi.org/10.1186/s11671-021-03580-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319264PMC
July 2021

The immune checkpoint regulator PD-L1 expression are associated with clinical progression in prostate cancer.

World J Surg Oncol 2021 Jul 16;19(1):215. Epub 2021 Jul 16.

Department of Urology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Guangxi Zhuang Autonomous Region, Nanning, 530021, China.

Background: The programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) have shown positive efficacy in several solid cancers due to their targeted antitumour effects. However, the frequency and clinical implication value in prostate cancer still remain unclear.

Methods: The PD-1/PD-L1 expression was detected by immunohistochemical (IHC) analysis in 96 retrospectively collected cases of prostatic cancer and 44 controls of benign prostatic hyperplasia (BPH). Its correlation with clinicopathological features including age, PSA level, Gleason score, lymph node metastasis, clinical T stage and risk factor grade in prostate cancer was also assessed.

Results: The PD-L1-positive expression was significantly higher in cancer cases compared with benign tissues, whereas no difference in PD-1 positive expression was found. Moreover, the PD-L1 expression in tumour cells or lymphocytes was associated with Gleason score, but not related to age, preoperative PSA level, clinical T-stage, lymph node metastasis and grade of risk factors. In addition, no association between the positive expression of PD-1 and PD-L1 in tumour cells and lymphocytes was found.

Conclusions: The expression of PD-L1 not PD-1 is highly prevalent in prostate cancer. PD-L1 is closely related to Gleason score and may be a co-factor associated with the progression of prostate cancer.
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http://dx.doi.org/10.1186/s12957-021-02325-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285882PMC
July 2021

Ceftazidime-Avibactam in Combination with In Vitro Non-susceptible Antimicrobials Versus Ceftazidime-Avibactam in Monotherapy in Critically Ill Patients with Carbapenem-Resistant Klebsiella Pneumoniae Infection: A Retrospective Cohort Study.

Infect Dis Ther 2021 Sep 9;10(3):1699-1713. Epub 2021 Jul 9.

Department of Pharmacy, Ruijin Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: No clinical study has investigated the use of ceftazidime-avibactam combination schemes with an in vitro non-susceptible antimicrobial that could be superior to ceftazidime-avibactam monotherapy against carbapenem-resistant Klebsiella pneumoniae.

Methods: We performed a retrospective cohort study at two tertiary hospitals in China for patients with carbapenem-resistant Klebsiella pneumoniae infection treated with ceftazidime-avibactam for at least 72 h. A Cox proportional hazards regression model was used to evaluate covariates that potentially affected 30-day mortality.

Results: Sixty-two patients were eligible for our study; 41 (66.1%) received ceftazidime-avibactam combination therapy and 21 (33.9%) received ceftazidime-avibactam monotherapy. The overall 30-day mortality was 33.9% (21 patients): 24.4% (10/41) and 47.6% (11/21), P = 0.028, in combination and monotherapy groups, respectively. Combination therapy was significantly associated with lower 30-day mortality (Hazard ratio, 0.167; 95% Confidence Interval, 0.060-0.465, P = 0.001). At the same time, a higher APACHE II score, use of vasoactive drugs and comorbidity of organ transplantation were considered factors that increased mortality. The propensity score showed no significant alterations with other variables after adding it to the final model. In the subgroup analysis, the protective effect was revealed when combined with carbapenems, tigecycline or fosfomycin were applied, and in the following subgroups of patients: with sepsis, with creatinine clearance > 50 mL/min, stayed in the intensive care unit ≤ 30 days or underwent mechanical ventilation.

Conclusions: Ceftazidime-avibactam combined with another in vitro non-susceptible antimicrobial, especially carbapenems, fosfomycin and tigecycline, could significantly decrease the 30-day mortality rate for critically ill patients with carbapenem-resistant Klebsiella pneumoniae infection. Further investigation should be carried out to confirm this conclusion and identify autofit antimicrobials in ceftazidime-avibactam combination schemes.
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http://dx.doi.org/10.1007/s40121-021-00479-7DOI Listing
September 2021

Abscisic acid receptors are involves in the Jasmonate signaling in .

Plant Signal Behav 2021 Oct 5;16(10):1948243. Epub 2021 Jul 5.

Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.

The phytohormones jasmonates (JAs) act as important molecules of elicitors for the chlorophyll degradation and anthocyanin biosynthesis. JAs do usually not act independently but integrate in complex networks linking to other hormonal signaling transduction. Here, the crosstalk was detected between the JAs (jasmonic acid) and abscisic acid (ABA) signaling pathways in the mediation of chlorophyll degradation and anthocyanin biosynthesis. In this study, we found that the ABA receptor mutants, (1124) and (112458) showed less level of chlorophyll and anthocyanin than the wild-type plants, while gain-of-function of transgenic lines inhibited chlorophyll degradation and enhanced anthocyanin accumulation after MeJA treatment. The amidohydrolases, including and and cytochrome P450 (), encoding JA-Ile catabolism were markedly depressed by ABA receptors. While transcripts of the enzymes for activation of anthocyanin biosynthesis pathway were analyzed, the results indicating that JA biosynthetic genes, including allene oxide synthase ( and were enhanced by the link of JAs and ABA receptors. Moreover, the ABA receptors are also involved in JAs signal transduction through the regulation of and transcripts. These findings elucidate a connection between a core component of the ABA signaling pathway and JA responses.
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http://dx.doi.org/10.1080/15592324.2021.1948243DOI Listing
October 2021

Based on a Decision Tree Model for Exploring the Risk Factors of Smartphone Addiction Among Children and Adolescents in China During the COVID-19 Pandemic.

Front Psychiatry 2021 8;12:652356. Epub 2021 Jun 8.

Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.

Smartphone addiction has emerged as a major concern among children and adolescents over the past few decades and may be heightened by the outbreak of COVID-19, posing a threat to their physical and mental health. Then we aimed to develop a decision tree model as a screening tool for unrecognized smartphone addiction by conducting large sample investigation in mainland China. The data from cross-sectional investigation of smartphone addiction among children and adolescents in mainland China ( = 3,615) was used to build models of smartphone addiction by employing logistic regression, visualized nomogram, and decision tree analysis. Smartphone addiction was found in 849 (23.5%) of the 3,615 respondents. According to the results of logistic regression, nomogram, and decision tree analyses, Internet addiction, hours spend on smartphone during the epidemic, levels of clinical anxiety symptoms, fear of physical injury, and sex were used in predictive model of smartphone addiction among children and adolescents. The C-index of the final adjusted model of logistic regression was 0.804. The classification accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and AUC area of decision tree for detecting smartphone addiction were 87.3, 71.4, 92.1, 73.5, 91.4, and 0.884, respectively. It was found that the incidence of smartphone addiction among children and adolescents is significant during the epidemic. The decision tree model can be used to screen smartphone addiction among them. Findings of the five risk factors will help researchers and parents assess the risk of smartphone addiction quickly and easily.
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http://dx.doi.org/10.3389/fpsyt.2021.652356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217434PMC
June 2021

Based on a Decision Tree Model for Exploring the Risk Factors of Smartphone Addiction Among Children and Adolescents in China During the COVID-19 Pandemic.

Front Psychiatry 2021 8;12:652356. Epub 2021 Jun 8.

Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.

Smartphone addiction has emerged as a major concern among children and adolescents over the past few decades and may be heightened by the outbreak of COVID-19, posing a threat to their physical and mental health. Then we aimed to develop a decision tree model as a screening tool for unrecognized smartphone addiction by conducting large sample investigation in mainland China. The data from cross-sectional investigation of smartphone addiction among children and adolescents in mainland China ( = 3,615) was used to build models of smartphone addiction by employing logistic regression, visualized nomogram, and decision tree analysis. Smartphone addiction was found in 849 (23.5%) of the 3,615 respondents. According to the results of logistic regression, nomogram, and decision tree analyses, Internet addiction, hours spend on smartphone during the epidemic, levels of clinical anxiety symptoms, fear of physical injury, and sex were used in predictive model of smartphone addiction among children and adolescents. The C-index of the final adjusted model of logistic regression was 0.804. The classification accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and AUC area of decision tree for detecting smartphone addiction were 87.3, 71.4, 92.1, 73.5, 91.4, and 0.884, respectively. It was found that the incidence of smartphone addiction among children and adolescents is significant during the epidemic. The decision tree model can be used to screen smartphone addiction among them. Findings of the five risk factors will help researchers and parents assess the risk of smartphone addiction quickly and easily.
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http://dx.doi.org/10.3389/fpsyt.2021.652356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217434PMC
June 2021

Diverse Right Ventricular Remodeling Evaluated by MRI and Prognosis in Eisenmenger Syndrome With Different Shunt Locations.

J Magn Reson Imaging 2021 Jun 21. Epub 2021 Jun 21.

Department of Cardiology, West China Hospital, Sichuan University, Chengdu, PR China.

Background: Congenital shunt location is related to Eisenmenger syndrome (ES) survival. Moreover, right ventricular (RV) remodeling is associated with poor survival in pulmonary hypertension.

Purpose: To investigate RV remodeling using comprehensive magnetic resonance imaging (MRI) techniques and identify its relationship with prognosis in ES subgroups classified by shunt location.

Study Type: Prospective observational study.

Population: Fifty-four adults with ES (16 with pre-tricuspid shunt and 38 with post-tricuspid shunt).

Field Strength/sequence: 3.0 T/cine MRI with balanced steady-state free precession sequence, late gadolinium enhancement with inversion recovery segmented gradient echo sequence and phase-sensitive reconstruction, and T1 mapping with modified Look-Locker inversion recovery sequence.

Assessment: Demographics, clinical characteristics, hemodynamics, RV remodeling features (morphology, systolic function, RV-pulmonary artery (PA) coupling and myocardial fibrosis), and prognosis were compared between ES subgroups. The adverse endpoint was all-cause mortality or readmission for heart failure.

Statistical Tests: The independent samples t-test, Fisher's exact test or Chi-squared test, and the Kaplan-Meier method were used. P < 0.05 was considered significant.

Results: Compared to patients with post-tricuspid shunt, patients with pre-tricuspid shunt were significantly older and had higher N-terminal pro-B-type natriuretic peptide concentrations and poorer exercise tolerance. Pre-tricuspid shunt showed significantly larger RV dimensions (end-diastolic volume index: 185.81 ± 37.49 vs. 98.20 ± 36.26 mL/m ), worse RV ejection fraction (23.54% ± 12.35% vs. 40.82% ± 10.77%), and RV-PA decoupling (0.35 ± 0.31 vs. 0.72 ± 0.29). Biventricular myocardial fibrosis was significantly more severe in pre-tricuspid shunt than post-tricuspid shunt (extracellular volume, left ventricle: 35.85% ± 2.58% vs. 29.10% ± 5.20%; RV free wall: 30.93% ± 5.65% vs. 26.75% ± 5.15%). In addition, pre-tricuspid shunt demonstrated a significantly increased risk of adverse endpoint (hazard ratio: 2.938, 95% confidence interval: 1.204-7.172).

Data Conclusion: ES with pre-tricuspid shunt might be a unique subtype with worse clinically decompensated RV remodeling and poor prognosis.

Level Of Evidence: 2 Technical Efficacy Stage: 5.
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http://dx.doi.org/10.1002/jmri.27791DOI Listing
June 2021

Association of Extracellular Signal-Regulated Kinase Genes With Myopia: A Longitudinal Study of Chinese Children.

Front Genet 2021 27;12:654869. Epub 2021 May 27.

The Eye Hospital, Wenzhou Medical University, Wenzhou, China.

Objective: The present study was designed to investigate whether the extracellular signal-regulated kinase (ERK) signaling pathway, a downstream component of dopamine signaling, is involved in myopia among Chinese children.

Methods: During a 3.5-year follow-up, 488 primary school students were enrolled in this study. Non-cycloplegic spherical equivalent refraction (SE) and other ocular parameters were assessed. Four variants of four genes in the ERK signaling pathway were selected: rs6495367, rs1550870, rs11178469, and rs6554163. SNPscan was used to genotype single-nucleotide polymorphisms (SNPs). PLINK software was used to assess the associations of the genetic variants with the occurrence or development of myopia, SE, and other ocular parameters. We created a protein-protein interaction (PPI) network and microRNA (miRNA)-gene network using String and Cytoscape and conducted enrichment analyses on the genes in these networks.

Results: In total, 426 children (baseline age: 7.28 ± 0.26 years; 236 (55.4%) boys and 190 girls) wereenrolled. After adjusting for confounding factors with 10,000 permutations, children with the CT or TT genotype of rs155087 were more susceptible to myopia than those with the CC genotype (adjusted = 0.011). Additionally, rs155087 was correlated with significant myopic shift and increasing axial length (AL) and lens thickness (LT) but had a negative effect on central corneal thickness (CCT). rs6495367 was negatively associated with myopic shift (additive: adjusted = 0.034; dominant: adjusted = 0.020), myopic SE and AL. rs6554163 TA or AA was negatively associated with increasing LT (adjusted = 0.033). Evaluation of the effects of SNP-SNP combinations on incident myopia revealed a statistically significant one-locus model: rs1550870 [cross-validation consistency (CVC) = 10/10, adjusted = 0.0107]. The genes in the PPI and miRNA-gene interaction networks were subjected to enrichment analyses, which suggested that these genes are involved mainly in eye development and dopaminergic synapse-related processes.

Conclusion: We identified genetic variants of crucial ERK signaling pathway genes that were significantly correlated with myopia and ocular parameter alterations in Chinese children. A combination of gene and miRNA functional analyses with enrichment analyses highlights the regulatory effects associated with ocular development and dopamine biological functions. This study offers novel clues to understand the role of dopamine in the molecular mechanisms of myopia.
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http://dx.doi.org/10.3389/fgene.2021.654869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191505PMC
May 2021

Treatment and outcome patterns of patients with Waldenström's macroglobulinemia: a large, multicenter retrospective review in China.

Leuk Lymphoma 2021 Jun 9:1-8. Epub 2021 Jun 9.

Department of Hematology, Hubei, China.

In this study, we aimed to investigate treatment options and the prognosis of patients with WM in China. This retrospective study included 1141 patients diagnosed with symptomatic WM between January 2003 and December 2019 at 35 tertiary hospitals in 22 provinces of China. Fifty-four patients (7.3%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, 395 (53.8%) received other combination regimens without rituximab, and 21 (2.9%) received ibrutinib. Using a multivariable Cox regression model, age > 65 years old, platelets <100 × 10/L, serum albumin <3.5 g/dl, β2 microglobulin concentration ≥4 mg/L and LDH ≥250 IU/L predicted poor OS. In summary, our study showed that frontline treatment choices for WM are widely heterogeneous. We validated most of the established prognostic factors in the rIPSS (age >65 years, LDH ≥250 IU/L, ALB <3.5 g/dl and β2 microglobulin ≥4 mg/L) together with PLT ≤ 100 × 10/L indicate a poor prognosis for patients with WM.
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http://dx.doi.org/10.1080/10428194.2021.1938030DOI Listing
June 2021

Expression and function of Smad7 in autoimmune and inflammatory diseases.

J Mol Med (Berl) 2021 May 31. Epub 2021 May 31.

Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, 518036, Guangdong, China.

Transforming growth factor-β (TGF-β) plays a critical role in the pathological processes of various diseases. However, the signaling mechanism of TGF-β in the pathological response remains largely unclear. In this review, we discuss advances in research of Smad7, a member of the I-Smads family and a negative regulator of TGF-β signaling, and mainly review the expression and its function in diseases. Smad7 inhibits the activation of the NF-κB and TGF-β signaling pathways and plays a pivotal role in the prevention and treatment of various diseases. Specifically, Smad7 can not only attenuate growth inhibition, fibrosis, apoptosis, inflammation, and inflammatory T cell differentiation, but also promotes epithelial cells migration or disease development. In this review, we aim to summarize the various biological functions of Smad7 in autoimmune diseases, inflammatory diseases, cancers, and kidney diseases, focusing on the molecular mechanisms of the transcriptional and posttranscriptional regulation of Smad7.
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http://dx.doi.org/10.1007/s00109-021-02083-1DOI Listing
May 2021

The Association of Morning Surge and Night-Time Dipping Blood Pressure with Significant and Complex Coronary Artery Lesions.

High Blood Press Cardiovasc Prev 2021 May 31. Epub 2021 May 31.

Department of Cardiology, Lanzhou University Second Hospital, 82 Cuiyingmen St, Lanzhou, 730030, Gansu, People's Republic of China.

Introduction: Hypertension responsible for more than 10 million deaths annually worldwide and abnormal diurnal blood pressure (BP) variation is associated with cardiovascular events.

Aim: This study aimed to investigate the association between the 24-h ambulatory night BP dipping and morning BP surge (MS) with characteristic of coronary artery lesions that may contribute cardiovascular events and mortality burden.

Methods: A cross sectional study over 1-year, collected 263 cases of hypertensive (80%) and non-hypertensive patients, aged 61 ± 10 years, who undergoing invasive coronary angiography (CAG) and 24-h ambulatory BP monitoring admitted to cardiology department complain of chest pain. The night-time/day-time dip and sleep-trough MS were calculated. Non-dipper status was considered when night-time/day-time dip < 10%, and significant coronary lesion (SCL) when ≥ 50 % stenosis in 1.5 mm vessels. The SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score was used to quantify the complexity of SCL.

Result: The mean morning systolic BP (SBP) surge was higher in the high SYNTAX Score subgroup than low and intermediate subgroups (25 ± 11 vs 17 ± 13 and 10 ± 10 mmHg, p < 0.010). Non-dipper SBP status was more frequently in patients with SCL than non-SCL (p < 0.019). In ordinal regression, hypertension was independent predictor of SCL (odd ratio: 0.40, p < 0.003), the night-time/day-time BP dip was independent predictor of being in a higher SYNTAX score subgroup (systolic odd ratio: 0.88, diastolic odd ratio: 1.14 p < 0.05).

Conclusion: Hypertension is associated with SCL and the night-time/day-time BP dip as a continuous variable is associated with complex coronary lesion. Non-dipping as categorical variable and morning BP surge were not independent predictors of significant or complex coronary lesions.
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http://dx.doi.org/10.1007/s40292-021-00463-9DOI Listing
May 2021

Association of Myopia and Genetic Variants of and in the TGF-β Signaling Pathway: A Longitudinal Study in Chinese School-Aged Children.

Front Cell Dev Biol 2021 28;9:628182. Epub 2021 Apr 28.

Eye Hospital, Wenzhou Medical University, Wenzhou, China.

Background: Myopia is a complex multifactorial condition which involves several overlapping signaling pathways mediated by distinct genes. This prospective cohort study evaluated the associations of two genetic variants in the TGF-β signaling pathway with the onset and progression of myopia and ocular biometric parameters in Chinese school-aged children.

Methods: A total of 556 second grade children were examined and followed up for 3.5 years. Non-cycloplegic refraction and ocular biometric parameters were measured annually. Multivariate regression analysis was used to assess the effect of the rs10760673 and rs7550232 variants on the occurrence and progression of myopia. A 10,000 permutations test was used to correct for multiple testing. Functional annotation of single nucleotide polymorphisms (SNPs) was performed using RegulomeDB, HaploReg, and rVarBase.

Results: A total of 448 children were included in the analysis. After adjustments for gender, age, near work time and outdoor time with 10,000 permutations, the results indicated that the C allele and the AC or CC genotypes of rs7550232 adjacent to were associated with a significantly increased risk of the onset of myopia in two genetic models (additive: ' = 0.022; dominant: ' = 0.025). Additionally, the A allele and the AA or AG genotypes of rs10760673 of were associated with a significant myopic shift (additive: ' = 0.008; dominant: ' = 0.028; recessive: ' = 0.027). Furthermore, rs10760673 was associated with an increase in axial length (AL) (' = 0.013, β = 0.03) and a change in the ratio of AL to the corneal radius of curvature (AL/CRC) (' = 0.031, β = 0.003). Analysis using RegulomeDB, HaploReg, and rVarBase indicated that rs7550232 is likely to affect transcription factor binding, any motif, DNase footprint, and DNase peak.

Conclusion: The present study indicated that rs10760673 and rs7550232 may represent susceptibility loci for the progression and onset of myopia, respectively, in school-aged children. Associations of the variants of the and genes with myopia may be mediated by the TGF-β signaling pathway; this hypothesis requires validation in functional studies. This trial was registered as ChiCTR1900020584 at www.Chictr.org.cn.
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http://dx.doi.org/10.3389/fcell.2021.628182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115727PMC
April 2021

Co-Occurring Alteration of NOTCH and DDR Pathways Serves as Novel Predictor to Efficacious Immunotherapy in NSCLC.

Front Oncol 2021 22;11:659321. Epub 2021 Apr 22.

Cancer Center, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Although immune checkpoint inhibitors (ICIs) have shown remarkable benefit for treatment of advanced non-small lung cancer (NSCLC), only a minority of patients can achieve durable responses and the most patients produce an ultra-rapid progressive disease. Here, we collected the availably published datasets and mined the determinants of response to immunotherapy on pathway levels. One hundred six NSCLC patients treated with immunotherapy were combined from Rizvi et al. and Hellman et al. studies (whole exon sequencing). Two independent validation datasets consisted of the MSKCC cohort (targeted sequencing) and data by Anagnostou and colleagues (whole exon sequencing). The Cancer Genome Atlas (TCGA) somatic mutation and gene expression data were applied to explore the immunobiology features. In the first combined cohort, we detected NOTCH pathway altered in 71% patients with durable clinical benefit (DCB) while only 36% among no durable benefit (NDB) (p = 0.005). Compared to NDB group, co-occurrence of NOTCH and at least two DDR (co-DDR) pathway was discovered in DCB group and contributed to a prolonged progression-free survival (PFS) [22.1 3.6 months, p < 0.0001, HR, 0.34, 95% confidence interval (CI), 0.2-0.59]. In two independent datasets, co-occurrence of NOTCH+/co-DDR+ was also validated to be a better immunotherapy efficacy [Cohort 2: 13 6 months, p = 0.034, HR, 0.55, 95% CI, 0.31-0.96; Cohort 3: 21 11 months, p = 0.067, HR, 0.45, 95% CI, 0.18-1.1]. By analyzing TCGA cohort, we found patients with coexisting NOTCH+/co-DDR+ pathway had a higher TMB, more infiltration of CD4+T cells. Overall, co-occurrence of NOTCH and co-DDR pathway reflect a better immunotherapy efficacy in advanced NSCLC. This genomic predictor show promise in stratifying patients that suit for immunotherapy for future clinical practice.
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http://dx.doi.org/10.3389/fonc.2021.659321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100434PMC
April 2021

Selectivity and Targeting of G-Quadruplex Binders Activated by Adaptive Binding and Controlled by Chemical Kinetics.

Angew Chem Int Ed Engl 2021 07 1;60(28):15340-15343. Epub 2021 Jun 1.

MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, State Key Laboratory of Oncology in South China, Sun Yat-Sen University, No. 135, Xingang Xi Road, 510275, Guangzhou, China.

G-quadruplexes (G4s) are prevalent in oncogenes and are potential antitumor drug targets. However, binding selectivity of compounds to G4s still faces challenges. Herein, we report a platinum(II) complex (Pt1), whose affinity to G4-DNA is activated by adaptive binding and selectivity controlled by binding kinetics. The resolved structure of Pt1/VEGF-G4 (a promoter G4) shows that Pt1 matches 3'-G-tetrad of VEGF-G4 through Cl -dissociation and loop rearrangement of VEGF-G4. Binding rate constants are determined by coordination bond breakage/formation, correlating fully with affinities. The selective rate-determining binding step, Cl -dissociation upon G4-binding, is 2-3 orders of magnitude higher than dsDNA. Pt1 potently targets G4 in living cells, effectively represses VEGF expression, and inhibits vascular growth in zebrafish. We show adaptive G4-binding activation and controlled by kinetics, providing a complementary design principle for compounds targeting G4 or similar biomolecules.
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http://dx.doi.org/10.1002/anie.202104624DOI Listing
July 2021

Comparison of the antiviral effect of Arbidol and Chloroquine in treating COVID-19.

Ann Palliat Med 2021 Mar;10(3):3307-3312

Department of Respiratory and Critical Care Medicine, The 4th Hospital of Kunming City, Anning, China.

Background: The novel coronavirus disease 2019 (COVID-19) was broken out in December 2019 and soon became a global health emergency. Effective treatment for COVID-19 is urgently needed. In the present study, we aimed to evaluate the antiviral effect of Arbidol vs. Chloroquine in treating COVID-19.

Methods: We retrospectively analyzed 62 patients with COVID-19 diagnosed according to the guidelines for diagnosis and treatment of COVID-19 in China. They were divided into two groups depending on the antiviral drugs that they received. Participants in the Arbidol group (n=42) received 0.2 g Arbidol, tid for 10 days,and those in Chloroquine group (n=20) received 500 mg Chloroquine, bid for 10 days. The coronavirus negative conversion time and the length of hospital stay were analyzed and compared between the two groups.

Results: There was no significant difference in demographic and clinical characteristics between the two groups. After antiviral treatment, the nasopharyngeal specimen negative conversion time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the length of hospital stay in the Arbidol group were significantly shorter than those in the Chloroquine group (18.50 vs. 25.05 days, P=0.001; 23.52 vs. 28.75 days, P=0.001). Adverse events observed during the antiviral treatment period were comparable between the two groups. Overall, 3 (7.14%) participants in the Arbidol group and 4 (20.0%) in the Chloroquine group experienced adverse events during antiviral treatment.

Conclusions: These results suggest that Arbidol is advantageous over Chloroquine in terms of the SARS-CoV-2 negative conversion and the length of hospital stay in treating COVID-19 patients.
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http://dx.doi.org/10.21037/apm-21-400DOI Listing
March 2021

Identifying vegetation restoration effectiveness and driving factors on different micro-topographic types of hilly Loess Plateau: From the perspective of ecological resilience.

J Environ Manage 2021 Jul 10;289:112562. Epub 2021 Apr 10.

School of Public Administration and Policy, Renmin University of China, Beijing, 100872, China. Electronic address:

Vegetation restoration is an important way to improve the sustainability of the ecosystem in the hilly Loess Plateau. The variation of vegetation coverage, caused by the combined effects of meteorological factors and human activities, reflects the succession trend of regional ecosystems. Given the complexity and the diversity of landform in the hilly Loess Plateau, vegetation restoration is more affected by topographic factors. Nevertheless, few studies have considered the characteristics and trends of vegetation restoration under different micro-topographic types in the long-time series. From the perspective of ecological resilience based on the fractional vegetation cover (FVC), the trend, the hurst exponent, and the geographical spatial research were used to analyze the variation and future sustainability of vegetation restoration on different micro-topographic types for 20 years. Besides, the spatial autocorrelation, principal component analysis (PCA) and geographically weighted regression (GWR) were applied to identify the driving factors of vegetation restoration. The results showed: (1) the average of the overall regional vegetation coverage was 61.32%, and only 0.95% of the regional vegetation was degraded in the past 20 years. However, in the future, 69.87% of the area would be degraded from improvement, and 0.52% would be significantly decreased; (2) the vegetation coverage in descending order was as follows: ridge area with shady and steep slope, gully area with shady and steep slope, ridge area with sunny and steep slope, gully area with sunny and steep slope, gully area with shady and gentle slope, ridge area with shady and gentle slope, ridge area with sunny and gentle slope, gully area with sunny and gentle slope, valley area; (3) the difference of vegetation degradation among micro-topography was remarkable, and the valley area and gully area with sunny and steep slope have the greatest decrease; (4) the primary factors affecting vegetation restoration in the hilly Loess Plateau were temperature, moisture, soil quality, and social economical condition, and the dominant factors were various under different micro-topographic types and villages. Therefore, it is necessary to adjust ecological engineering measures by comprehensively considering the regional differences among dominant factors of vegetation restoration.
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http://dx.doi.org/10.1016/j.jenvman.2021.112562DOI Listing
July 2021

Clinical characteristics and sociodemographic features of psychotic major depression.

Ann Gen Psychiatry 2021 Mar 26;20(1):24. Epub 2021 Mar 26.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No 11, Bei San Huan East Road, Chaoyang District, Beijing, 100029, China.

Background: Psychotic major depression (PMD) is a subtype of depression with a poor prognosis. Previous studies have failed to find many differences between patients with PMD and those with non-psychotic major depression (NMD) or schizophrenia (SZ). We compared sociodemographic factors (including season of conception) and clinical characteristics between patients with PMD, NMD, and schizophrenia. Our aim was to provide data to help inform clinical diagnoses and future etiology research.

Methods: This study used data of all patients admitted to Shandong Mental Health Center from June 1, 2016 to December 31, 2017. We analyzed cases who had experienced an episode of PMD (International Classification of Diseases, Tenth Revision codes F32.3, F33.3), NMD (F32.0-2/9, F33.0-2/9), and SZ (F20-20.9). Data on sex, main discharge diagnosis, date of birth, ethnicity, family history of psychiatric diseases, marital status, age at first onset, education, allergy history, and presence of trigger events were collected. Odds ratios (OR) were calculated using logistic regression analyses. Missing values were filled using the k-nearest neighbor method.

Results: PMD patients were more likely to have a family history of psychiatric diseases in their first-, second-, and third-degree relatives ([OR] 1.701, 95% confidence interval [CI] 1.019-2.804) and to have obtained a higher level of education (OR 1.451, 95% CI 1.168-1.808) compared with depression patients without psychotic features. Compared to PMD patients, schizophrenia patients had lower education (OR 0.604, 95% CI 0.492-0.741), were more often divorced (OR 3.087, 95% CI 1.168-10.096), had a younger age of onset (OR 0.934, 95% CI 0.914-0.954), less likely to have a history of allergies (OR 0.604, 95% CI 0.492-0.741), and less likely to have experienced a trigger event 1 year before first onset (OR 0.420, 95% CI 0.267-0.661). Season of conception, ethnicity, and sex did not differ significantly between PMD and NMD or schizophrenia and PMD.

Conclusions: PMD patients have more similarities with NMD patients than SZ patients in terms of demographic and clinical characteristics. The differences found between PMD and SZ, and PMD and NMD correlated with specificity of the diseases. Furthermore, allergy history should be considered in future epidemiological studies of psychotic disorders.
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http://dx.doi.org/10.1186/s12991-021-00341-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004453PMC
March 2021

Determination of the Isotopic Composition of Zirconium Using MC-ICPMS and a Regression Model for Mass Bias Correction.

Anal Chem 2021 Mar 18;93(12):5107-5113. Epub 2021 Mar 18.

National Research Council Canada, 1200 Montreal Road, Ottawa, Ontario K1A 0R6, Canada.

Measurements of zirconium isotopes provide insights into the formation of planetary bodies, dating nuclear explosions, or maintenance of nuclear reactors. Although many comparative measurements for the isotopic composition of zirconium have been performed using mass spectrometry, there is a lack of zirconium isotopic reference materials and only a single calibrated measurement has been reported to date by total evaporation thermal ionization mass spectrometry (TE-TIMS). In this study, we report an independent measurement of full zirconium isotopic composition in a new zirconium isotopic reference material by multicollector inductively coupled plasma MS using the regression method and two independent certified isotopic reference materials, NIST SRM 984 Rb and NIST SRM 987 Sr. Our results agree well with the recent TE-TIMS measurements and suggest a revision of the standard atomic weight of zirconium.
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http://dx.doi.org/10.1021/acs.analchem.0c04744DOI Listing
March 2021

Coding of Non-coding RNA: Insights Into the Regulatory Functions of Pri-MicroRNA-Encoded Peptides in Plants.

Front Plant Sci 2021 25;12:641351. Epub 2021 Feb 25.

Department of Plant Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.

Peptides composed of a short chain of amino acids can play significant roles in plant growth, development, and stress responses. Most of these functional peptides are derived by either processing precursor proteins or direct translation of small open reading frames present in the genome and sometimes located in the untranslated region sequence of a messenger RNA. Generally, canonical peptides serve as local signal molecules mediating short- or long-distance intercellular communication. Also, they are commonly used as ligands perceived by an associated receptor, triggering cellular signaling transduction. In recent years, increasing pieces of evidence from studies in both plants and animals have revealed that peptides are also encoded by RNAs currently defined as non-coding RNAs (ncRNAs), including long ncRNAs, circular RNAs, and primary microRNAs. Primary microRNAs (miRNAs) have been reported to encode regulatory peptides in , grapevine, soybean, and , called miRNA-encoded peptides (miPEPs). Remarkably, overexpression or exogenous applications of miPEPs specifically increase the expression level of their corresponding miRNAs by enhancing the transcription of the () genes. Here, we first outline the current knowledge regarding the coding of putative ncRNAs. Notably, we review in detail the limited studies available regarding the translation of miPEPs and their relevant regulatory mechanisms. Furthermore, we discuss the potential cellular and molecular mechanisms in which miPEPs might be involved in plants and raise problems that needed to be solved.
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http://dx.doi.org/10.3389/fpls.2021.641351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947200PMC
February 2021

Naoxintong accelerates diabetic wound healing by attenuating inflammatory response.

Pharm Biol 2021 Dec;59(1):252-261

State Key Laboratory of Component-based Chinese Medicine, Tianjin, China.

Context: Naoxintong (NXT), a prescribed traditional Chinese medicine, widely used in cerebrovascular and cardiovascular diseases, could be effective in diabetic wounds.

Objective: This study evaluates the wound healing activity of NXT by employing an excisional wound splinting model.

Materials And Methods: NXT was dissolved in saline and given daily by gavage. Wounds were induced at the dorsum of non-diabetic (db/+) and diabetic (db/db) mice and treated with saline or 700 mg/kg/d NXT for 16 days. Wound closure was measured every four days. Extracellular matrix (ECM) remodelling, collagen deposition, leukocyte infiltration and expression of Col-3, CK14, CXCL1, CXCL2, MPO, Ly6G, CD68, CCR7, CD206, p-JAK1, p-STAT3 and p-STAT6 was analysed.

Results: NXT significantly accelerated rate of wound closure increased from 70% to 84%, accompanied by up-regulation of collagen deposition and ECM at days 16 post-injury. Moreover, NXT alleviated neutrophil infiltration, accompanied by down-regulation of CXCL1 and CXCL2 mRNA expression. In addition, NXT markedly augmented neutrophil efferocytosis. In diabetic wounds, the levels of M1 marker gene (CCR7) increased, while M2 marker gene (CD206) decreased, demonstrating a pro-inflammatory shift. Application of NXT increased M2 macrophage phenotype in db/db mice. Mechanistically, NXT treatment increased expression level of p-STAT3 and p-STAT6 at days 3 post-injury, indicating NXT mediated macrophages towards M2 phenotype and alleviated inflammation in diabetic wounds by activation of STAT3 and STAT6.

Conclusions: Our study provides evidence that NXT accelerates diabetic wound healing by attenuating inflammatory response, which provides an important basis for use of NXT in the treatment of chronic diabetic wound healing.
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http://dx.doi.org/10.1080/13880209.2021.1877735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946048PMC
December 2021

Author Response to Comment on: Dynamic Adsorption of Sulfamethoxazole from Aqueous Solution by Lignite Activated Coke.

Materials (Basel) 2021 Feb 11;14(4). Epub 2021 Feb 11.

Beijing Engineering Research Center of Sustainable Urban Sewage System Construction and Risk Control, Beijing University of Civil Engineering and Architecture,100044 Beijing, China.

The authors would like to thank the comment by Diego M. Juela for contributing to helpful scientific discussions and correction suggestions, and to also express thanks to the editors.
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http://dx.doi.org/10.3390/ma14040868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918909PMC
February 2021

Identification of a novel genomic resistance island PmGRI1-STP3 and an SXT/R391 integrative conjugative element in Proteus mirabilis of swine origin in China.

J Glob Antimicrob Resist 2021 06 2;25:77-81. Epub 2021 Mar 2.

Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, Key Laboratory of Bio-resources and Eco-environment, Ministry of Education, College of Life Science, Sichuan University, Chengdu, China; Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, Chengdu, Sichuan, China. Electronic address:

Objectives: This study aimed to determine the genetic environment of antimicrobial resistance genes in Proteus mirabilis strain STP3 isolated from a diarrhoeic pig on a swine farm in Sichuan Province, China.

Methods: Strain STP3 was subjected to antimicrobial susceptibility testing. Illumina MiSeq (200× coverage) and Nanopore PromethION (100× coverage) platforms were used for genome sequencing. A conjugation experiment was performed to determine the transferability and stability of antimicrobial resistance genes in this strain.

Results: The assembled circular genome of P. mirabilis STP3 was 4 115 975 bp with a GC content of 39.58%; no plasmid sequence was detected. A novel genomic resistance island (PmGRI1-STP3) and an SXT/R391 integrative conjugative element (ICE) variant (ICEPmiChnSTP3) were characterised in P. mirabilis STP3. PmGRI1-STP3 of 52.7 kb was located at the 3' end of tRNA-Sec and shared the greatest identity with PmGRI1-C55 (54% coverage, 99.99% identity). PmGRI1-STP3 carried 16 resistance genes, including the clinically important extended-spectrum β-lactamase (ESBL) gene bla. ICEPmiChnSTP3 was inserted into the prfC gene. It carried 18 resistance genes, including the rRNA methyltransferase gene cfr and the fluoroquinolone resistance gene aac(6')-Ib-cr. A class 2 integron (dfrA1-sat2-aadA1) was also identified on transposon Tn7. Mobilisation experiments indicated that ICEPmiChnSTP3 was conjugally mobilised to Escherichia coli. However, PmGRI1-STP3 appeared to lose its mobilisation ability.

Conclusion: The identification of two genomic islands (GIs) in this study suggested that genetic elements might be key mediators for resistance gene acquisition in P. mirabilis and that IS26-mediated rearrangements promote the diversity of GIs.
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http://dx.doi.org/10.1016/j.jgar.2021.02.018DOI Listing
June 2021

Low Power, Low Temperature and Atmospheric Pressure Plasma-Induced Polymerization: Facile Synthesis and Crystal Regulation of Covalent Organic Frameworks.

Angew Chem Int Ed Engl 2021 Apr 22;60(18):9984-9989. Epub 2021 Mar 22.

Analytical & Testing Center, Sichuan University, Chengdu, Sichuan, 610064, China.

Low temperature and atmospheric pressure plasma-induced polymerization was demonstrated as a fast and facile strategy for tailoring of packing phase of COF-1 as well as preparing diverse covalent organic frameworks (COFs) including both two-dimensional (2D) COFs and three-dimensional (3D) COFs. By regulating the solvents, the fast construction of well-ordered AB staggered COF-1 and AA eclipsed COF-1 was facilely realized in minutes. The plasma approach presented here led to the rapid preparation of eight classical 2D COFs, including boronate ester-linkage (COF-5, COF-8 and COF-10), azine-linkage (NUS-2), β-ketoenamine-linkage (TpPa, TPBD), imine-linkage (ILCOF-1, Py-COF), and 3D-COF-102 (boroxine linkage) in less than 1 hour. Different from conventional methods, the proposed methodology required much less time, lower power, no extra heating, inert-gas protection and pressure. The fast nucleation and growth of COFs with good crystallinity, morphology and thermal stability can be achieved under mild conditions.
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http://dx.doi.org/10.1002/anie.202102051DOI Listing
April 2021

The relationship of severity in diastasis recti abdominis and pelvic floor dysfunction: a retrospective cohort study.

BMC Womens Health 2021 02 15;21(1):68. Epub 2021 Feb 15.

Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, GuangDong Province, China.

Background: Diastasis of rectus abdominis (DRA) refers to a separation of the rectus abdominis from the linea alba. This study aimed to investigate the association with the severity of DRA for developing pelvic floor dysfunction among women during the first year postpartum.

Methods: This is a retrospective cohort study which collected data from 229 postpartum women. DRA was defined as a separation of ≥ 20 mm at any point 4.5 cm above, at and 4.5 cm below the umbilicus. The data for analysis includes pelvic organ prolapse quantification (POP-Q), medical history of urinary incontinence (UI), the strength of rectus abdominis muscle and pelvic floor muscle. The differences in women with and without DRA were compared with independent samples t-test and Chi-square test.

Results: Prevalence of DRA was 82.6% during the first postpartum year. Cesarean section and multiple parturitions are recognized as risk factors for DRA due to the odds ratio in our study were 3.48 (95% CI 1.42-8.56), 3.20 (95% CI 1.59-6.45) respectively. There was no difference in the occurrence of UI and pelvic organ prolapse (POP) comparing women with and without DRA, even changing the cut-off values (inter-rectus distance = 20 mm, 30 mm, 40 mm, 50 mm) for determining DRA. The women with weak rectus abdominis muscle and pelvic floor muscle have no statistical difference in two group.

Conclusion: The relationship of the diastasis recti abdominis and pelvic floor dysfunction has no connection, even with the severity of inter-rectus distance increasing.
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http://dx.doi.org/10.1186/s12905-021-01194-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885475PMC
February 2021

Downregulation of caveolin-1 promotes murine breast cancer cell line progression by highly glycosylated CD147.

Anticancer Drugs 2021 06;32(6):626-634

Department of Immunology, School of Medicine, Nankai University.

Caveolin-1 (CAV-1) can extensively regulate lipid transportation, cell growth and cell death. In the present study, we revealed a novel function of CAV-1 in inhibiting glycosylation of other molecules in murine breast cancer cell line. After the silencing of CAV-1, we found that the mRNA and protein expressions of cluster of differentiation 147 (CD147) and its related molecules (MCT4, matrix metalloproteinase MMP2 and MMP9) increased in the breast cancer cells. Meanwhile, the migration and invasion of the breast cancer cells were significantly enhanced assessed by cell wound healing experiment and transwell assays. Further, the gelatin zymography and lactate assay in the cells also showed the strengthened enzyme activity of MMP9 and the increased extracellular lactate concentration, respectively, after the silencing of CAV-1. Notably, the glycosylation level of CD147 overtly increased after the inhibition of CAV-1 detected by Western Blot analysis, whereas upregulation of CAV-1 did the opposite. Therefore, the findings suggest that the downregulation of CAV-1 can promote breast cancer cell progression probably by highly glycosylated CD147.
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http://dx.doi.org/10.1097/CAD.0000000000001036DOI Listing
June 2021

Effect of high-dose intravenous vitamin C on point-of-care blood glucose level in septic patients: a retrospective, single-center, observational case series.

Curr Med Res Opin 2021 Apr 10;37(4):555-565. Epub 2021 Mar 10.

Department of Pharmacy, Shanghai JiaoTong University Medical School Affiliated Ruijin Hospital, Shanghai, China.

Introduction: High-dose vitamin C is an essential adjunctive drug for sepsis treatment. This study aimed to determine if high-dose vitamin C could lead to erroneous point-of-care glucose testing results.

Methods And Materials: This retrospective, single-center, observational case series involved septic patients treated with high-dose vitamin C. We monitored their paired point-of-care glucose and laboratory glucose levels for statistical analysis. The glucose oxidase-peroxidase colorimetric method and hexokinase spectrophotometric method were applied for point-of-care glucose and laboratory glucose monitoring, respectively. Parkes Consensus Error Grid Analysis was used to assess the clinical influence of paired blood glucose values. Subgroup analyses were conducted to explore the effect of different vitamin C dosages and various renal function levels on point-of-care glucose readings.

Results: During a 3-year period, 82 eligible septic patients who accepted at least three days of high-dose vitamin C treatment were included in this study. Compliance with ISO15197:2013 criteria was met in 30 (36.59%) paired values, a proportion considerably lower than the minimum criteria for accuracy. Subgroup analysis showed that worse renal function or higher vitamin C dosage could lead to greater bias in point-of-care glucose readings; however, these inaccuracies rarely represented a clinical risk.

Conclusions: High-dose intravenous ascorbate acid infusion may interfere with point-of-care glucose testing results. Thus, laboratory glucose measurements are recommended for more accurate results. Nonetheless, the inaccuracies magnitude of point-of-care glucose readings does not represent a significant clinical risk when physicians alter clinical action based on these results.
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http://dx.doi.org/10.1080/03007995.2021.1887832DOI Listing
April 2021

Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide.

Nat Commun 2021 02 8;12(1):866. Epub 2021 Feb 8.

State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, 200031, China.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat. The efficacy of several repurposed drugs has been evaluated in clinical trials. Among these drugs, a second-generation antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and Ad-ACE2-transduced mice. Tmprss2 knockout significantly inhibited SARS-CoV-2 infection in vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cells, however, such antiviral efficacy was lacking in human lung cells and organoids. Accordingly, enzalutamide showed no antiviral activity due to the AR-independent TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 regulatory locus in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19 through reducing TMPRSS2 expression in lung cells.
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http://dx.doi.org/10.1038/s41467-021-21171-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870838PMC
February 2021

Association between relationship characteristics and willingness to use PrEP among same-sex male couples: a cross-sectional actor-partner analysis in Guangzhou, China.

Int J STD AIDS 2021 Mar 8;32(3):228-238. Epub 2021 Feb 8.

Department of Medical Statistics & Sun Yat-sen Global Health Institute, School of Public Health and Institute of State Governance, 26469Sun Yat-sen University, Guangzhou, China.

The association between relationship characteristics and pre-exposure prophylaxis (PrEP) acceptability among same-sex male couples has been limitedly examined. Dyadic survey data of 139 concordant HIV-negative same-sex male couples in Guangzhou, China were collected. The willingness to use PrEP was measured assuming that the participant's partner was HIV-positive. The actor-partner interdependence model was used to examine how one's relationship characteristics affected the PrEP willingness of the subject and his partner. Most participants (79.5%) were willing to use PrEP. The two individuals of the couple were distinguished by sex role in relationship, namely one usually playing the insertive role and the other usually playing the receptive role in anal intercourse. The former was labeled as "top" and the latter labeled as "bottom". The PrEP willingness of the top partner increased when he would think his partner is having sex with other people if the partner requests condom use in relationship (AOR: 5.74, 95% CI: 1.10-29.87), and decreased when his partner would get violent upon condom use requests in relationship (AOR: 0.19, 95% CI: 0.04-0.88). The PrEP willingness of the bottom partner increased when he trusted his partner (AOR: 1.13, 95% CI: 1.02-1.25) and when he or his partner disclosed the relationship to parents (AOR: 10.57, 95% CI: 1.91-58.61). Considering the sex role and relationship characteristics in couple-based interventions are important to optimize PrEP uptake among HIV-discordant same-sex male couples.
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http://dx.doi.org/10.1177/0956462420953007DOI Listing
March 2021

Vitamin C supplementation is necessary for patients with coronavirus disease: An ultra-high-performance liquid chromatography-tandem mass spectrometry finding.

J Pharm Biomed Anal 2021 Mar 27;196:113927. Epub 2021 Jan 27.

Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China. Electronic address:

To administer vitamin C (VC) with precision to patients with the coronavirus disease (COVID-19), we developed an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to assess plasma VC concentrations. 31 patients with COVID-19 and 51 healthy volunteers were enrolled. VC stability was evaluated in blood, plasma, and precipitant-containing stabilizers. A proportion of 7.7 % of VC was degraded in blood at room temperature (RT) (approximately 20-25 °C) at 1.5 h post administration with respect to the proportion degraded at 0.5 h, but without statistical difference. VC was stable in plasma for 0.75 h at RT, 2 h at 4 °C, 5 days at -40 °C, and 4 h in precipitant-containing stabilizer (2 % oxalic acid) at RT. The mean plasma concentration of VC in patients with COVID-19 was 2.00 mg/L (0.5-4.90) (n = 8), which was almost 5-fold lower than that in healthy volunteers (9.23 mg/L (3.09. 35.30)) (n = 51). After high-dose VC treatment, the mean VC concentration increased to 13.46 mg/L (3.93. 34.70) (n = 36), higher than that in healthy volunteers, and was within the normal range (6-20 mg/L). In summary, we developed a simple UPLC-MS/MS method to quantify VC in plasma, and determined the duration for which the sample remained stable. VC levels in patients with COVID-19 were considerably low, and supplementation at 100 mg/kg/day is considered highly essential.
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http://dx.doi.org/10.1016/j.jpba.2021.113927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839397PMC
March 2021

SIRT1 Mediates HS-Ameliorated Diabetes-Associated Cognitive Dysfunction in Rats: Possible Involvement of Inhibiting Hippocampal Endoplasmic Reticulum Stress and Synaptic Dysfunction.

Neurochem Res 2021 Mar 3;46(3):611-623. Epub 2021 Feb 3.

Department of Neurology, Affiliated Nanhua Hospital, University of South China, No. 336, Dongfeng South Road, Hengyang, 421001, Hunan, People's Republic of China.

Diabetes-associated cognitive dysfunction (DACD) characterized by hippocampal injury increases the risk of major cerebrovascular events and death. Endoplasmic reticulum (ER) stress and synaptic dysfunction play vital roles in the pathological process. At present, no specific treatment exists for the prevention and/or the therapy of DACD. We have recently reported that hydrogen sulfide (HS) exhibits therapeutic potential for DACD, but the underlying mechanism has not been fully elucidated. Silent information regulator 1 (SIRT1) has been shown to play a role in regulating the progression of diabetes and is also indispensable for memory formation and cognitive performance. Hence, the present study was performed to explore whether SIRT1 mediates the protective effect of HS on streptozotocin (STZ)-induced cognitive deficits, an in vivo rat model of DACD, via inhibiting hippocampal ER stress and synaptic dysfunction. The results showed that administration of NaHS (an exogenous HS donor) increased the expression of SIRT1 in the hippocampus of STZ-induced diabetic rats. Then, results proved that sirtinol, a special blocker of SIRT1, abrogated the inhibition of NaHS on STZ-induced cognitive deficits, as appraised by Morris water maze test, Y-maze test, and Novel object recognition behavioral test. In addition, administration of NaHS eliminated STZ-induced ER stress as evidenced by the decreases in the expressions of ER stress-related proteins including glucose-regulated protein 78, C/EBP homologous protein, and cleaved caspase-12 in the hippocampus, while these effects of NaHS were also reverted by sirtinol. Furthermore, the NaHS-induced up-regulation of hippocampal synapse-related protein (synapsin-1, SYN1) expression in STZ-induced diabetic rats was also abolished by sirtinol. Taken together, these results demonstrated that SIRT1 mediates the protection of HS against cognitive dysfunction in STZ-diabetic rats partly via inhibiting hippocampal ER stress and synaptic dysfunction.
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http://dx.doi.org/10.1007/s11064-020-03196-8DOI Listing
March 2021
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