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Yating Zhang,1 Hongyan Wang,1 Jie Yang,2 Sanchun Wang,1 Weifang Tong,1 Bo Teng1 1Department of Otorhinolaryngology Head and Neck Surgery, the Second Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Bo Teng, Department of Otorhinolaryngology Head and Neck Surgery, the Second Hospital of Jilin University, No. 218 Ziqiang Street, Nanguan District, Changchun, Jilin Province, 130000, People’s Republic of China, Email tengbo1975@163.comPurpose: This investigation sought to elucidate the genetic underpinnings that connect obesity indicators, circulating blood lipid levels, adipokines levels and obstructive sleep apnea syndrome (OSAS), employing a bidirectional two-sample Mendelian randomization (MR) analysis that utilizes data derived from extensive genome-wide association studies (GWAS).Methods: We harnessed genetic datasets of OSAS available from the FinnGen consortium and summary data of four obesity indices (including neck circumference), seven blood lipid (including triglycerides) and eleven adipokines (including leptin) from the IEU OpenGWAS database. We primarily utilized inverse variance weighted (IVW), weighted median, and MR-Egger methods, alongside MR-PRESSO and Cochran’s Q tests, to validate and assess the diversity and heterogeneity of our findings.Results: After applying the Bonferroni correction, we identified significant correlations between OSAS and increased neck circumference (Odds Ratio [OR]: 3.472, 95% Confidence Interval [CI]: 1.954– 6.169, P= 2.201E-05) and decreased high-density lipoprotein (HDL) cholesterol levels (OR: 0.904, 95% CI: 0.858– 0.952, P= 1.251E-04). Concurrently, OSAS was linked to lower leptin levels (OR: 1.355, 95% CI: 1.069– 1.718, P= 0.012) and leptin receptor levels (OR: 0.722, 95% CI: 0.530– 0.996, P= 0.047). Sensitivity analyses revealed heterogeneity in HDL cholesterol and leptin indicators, but further multiplicative random effects IVW method analysis confirmed these correlations as significant (P< 0.05) without notable heterogeneity or horizontal pleiotropy in other instrumental variables.Conclusion: This investigation compellingly supports the hypothesis that OSAS could be a genetic predisposition for elevated neck circumference, dyslipidemia, and adipokine imbalance. These findings unveil potential genetic interactions between OSAS and metabolic syndrome, providing new pathways for research in this domain. Future investigations should aim to delineate the specific biological pathways by which OSAS impacts metabolic syndrome. Understanding these mechanisms is critical for developing targeted prevention and therapeutic strategies.Keywords: sleep disorders, metabolic syndrome, causal inference, GWAS

Wenxia Tong, Shuqiao Meng College of Physical Education, Yangzhou University, Yangzhou, People’s Republic of ChinaCorrespondence: Wenxia Tong, College of Physical Education, Yangzhou University, Yangzhou, 225000, People’s Republic of China, Tel +86-15003998013, Email tongwenxia@yzu.edu.cnBackground: Smartphones have become an important tool for college students’ study and life, but mobile phone addiction caused by excessive dependence use of cell phones can have serious negative impacts on college students’ mental health, life behaviors, and so on. It is urgent to explore the causes and influence mechanisms of college students’ cell phone addiction.Purpose: The purpose of this study was to investigate the relationship between physical exercise and mobile phone addiction among Chinese college students and the mediating role of negative affect and e-health literacy between the two.Methods: The stratified sampling method was used to investigate the physical activity, mobile phone addiction, negative emotion and e-health literacy of 4621 university students in Jiangsu Province using the Physical Activity Rating scale, Mobile Phone Addiction scale, Depression-anxiety-stress scale and E-Health Literacy scale, Thus the data were statistically analysed using SPSS 26.0 and AMOS 23.0.Results: (1) Physical exercise was significantly negatively correlated with mobile phone addiction and negative emotion among college students (r=− .713, P< 0.01; r=− .571, P< 0.01), and physical exercise was significantly positively correlated with e-health literacy (r=0.616, P< 0.01); (2) Negative emotion and e-health literacy played independent mediating roles between physical exercise and mobile phone addiction, respectively; (3) Negative emotion and e-health literacy played chain mediating roles between physical exercise and mobile phone addiction.Conclusion: This study explored the potential mechanisms of cell phone addiction in college students and found that physical activity can influence Internet addiction through the independent mediating effect including the chain mediating effect of negative emotions and e-health literacy. This study further reveals the mechanism of action of physical exercise affecting college students’ cell phone addiction, and provides some reference value for the prevention and intervention of college students cell phone addiction.Keywords: physical exercise, mobile phone addiction, negative emotion, e-health literacy, chain mediation

Fang Sun,1,* Zhigang Zhao,1,* Qiang Li,1 Xunmei Zhou,1 Yingsha Li,1 Hexuan Zhang,1 Zhencheng Yan,1 Hongbo He,1 Zhigang Ke,2 Yu Gao,2 Fan Li,2 Weidong Tong,2 Zhiming Zhu1 1Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing 400042, People’s Republic of China; 2Department of General Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiming Zhu Tel +86-23-6876-7849Fax +86-23-6870-5094Email zhuzm@yahoo.comBackground: High-sensitivity C-reactive protein (hs-CRP) has been regarded as a biomarker of low-degree inflammation in illness; however, whether CRP exerts its pathogenic effect on the cardiometabolic system remains unknown. Aside from the beneficial effects of metabolic surgery on cardiometabolic system, its impact on inflammation still worth examining. Thus, this study aims to investigate the effect of CRP on adipose and vascular cells, and their responses to metabolic surgery in obese diabetic patients.Patients and Methods: The expression of CRP and RAS- and ERK-related factors in the adipocytes and VSMCs were measured. Obese patients with type 2 diabetes who underwent metabolic surgery were followed up for 2 years thereafter. Laboratory tests, which included serum hs-CRP levels and visceral fat thickness (VFT), were obtained before and after surgery.Results: CRP administration significantly and dose-dependently increased the intracellular-free calcium concentration ([Ca2+]i) in cultured adipocytes and in the VSMCs. CRP administration significantly increased ACE, Ang II, AT1R and p-ERK expressions, but reduced ACE2 expression in both the adipocytes and VSMCs. Clinical study showed that VFT was closely associated with serum hs-CRP. Furthermore, VFT and serum hs-CRP were found to be highly associated with blood pressure. Finally, metabolic surgery remarkably decreased blood pressure, visceral fat and serum hs-CRP levels.Conclusion: CRP has a detrimental effect on cardiometabolic cells, aside from functioning merely as a biomarker. Serum hs-CRP levels are highly associated with hypertension and visceral obesity, which can be antagonized by metabolic surgery in obese diabetic patients.Keywords: CRP, metabolic surgery, type 2 diabetes

Weiwei Tong,1 Guanghui Tong,1 Dongyan Jin,1 Qingjie Lv2 1Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China Objective: To examine the relationship between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and susceptibility to lung cancer in a female Chinese population.Method: A hospital-based case-control study of 388 cases and 388 controls was conducted. Two polymorphisms in MTHFR were detected using TaqMan methods.Results: The MTHFR C677T polymorphism was associated with the risk of lung cancer and lung adenocarcinoma. Carriers with the TT genotype of C677T were observed to have an increased risk of lung cancer and lung adenocarcinoma (the ORs were 1.550 and 1.588, respectively). By contrast, the A1298C polymorphism had a negative relationship with the risk of lung cancer and lung adenocarcinoma; compared with the AA genotype carriers, the CC genotype carriers had a lower risk of lung cancer and adenocarcinoma in the female Chinese population (ORs were 0.302 and 0.215, respectively). In the stratified analyses, we observed only the A1298C polymorphism in the CC genotype carriers with a statistically significant reduction in the risk of non-small-cell lung cancer, compared to the AA genotype carriers. No significant statistical association was found between the MTHFR gene polymorphisms and risk of the residual subtype of lung cancer.Conclusion: This study provides evidence that the MTHFR C677T polymorphism may contribute to the development of lung cancer and lung adenocarcinoma in a female Chinese population. However, the MTHFR A1298C polymorphism may be associated with the decreasing risk of lung cancer. Keywords: MTHFR, single nucleotide polymorphism, lung cancer, genetic susceptibility

Jie Shen,1 Margot L Goodkin,2 Warren Tong,2 Mayssa Attar3 1Clinical Pharmacology, 2Clinical Development, 3Clinical Pharmacology, Metabolism and Immunology, Allergan plc, Irvine, CA, USA Purpose: Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP), but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed.Methods: New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve.Results: Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action) of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans), suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation.Conclusion: Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid, especially in the iris-ciliary body. Key findings from previous clinical studies suggest that by varying the concentration of benzalkonium chloride (a preservative with corneal penetration-enhancing properties), formulations of bimatoprost 0.01% can be administered once or twice daily. These findings support development of bimatoprost 0.01%-based fixed-dose combination therapies administered twice daily for patients who require multiple adjunctive medications to control their IOP. Keywords: bimatoprost, pharmacokinetics, glaucoma, intraocular pressure, hyperemia

Shen J, Goodkin ML, Tong W, Attar M. Clin Ophthalmol. 2017;11:1761–1767.On page 1765, Clinical correlation with evidence for use of bimatoprost twice daily in humans section, second column, last line, “−5.4 to −5.6 mm Hg” should have read “−5.4 to −6.0 mm Hg”.Read the original article

Shenghan Lai,1–4 Elliot K Fishman,2 Gary Gerstenblith,3 Jeffrey Brinker,3 Hong Tai,1 Shaoguang Chen,1 Ji Li,4 Wenjing Tong,1 Barbara Detrick,1 Hong Lai2 1Department of Pathology, 2Department of Radiology, 3Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA; 4Department of Epidemiology, John Hopkins University, Johns Hopkins Bloomberg School of Public Heath, Baltimore, MD, USA Objective: Patients with HIV infection are at increased risk for coronary artery disease (CAD), and growing evidence suggests a possible link between vitamin D deficiency and clinical/subclinical CAD. However, the relationship between vitamin D deficiency and coronary artery calcification (CAC), a sensitive marker for subclinical CAD, in those with HIV infection is not well investigated. Methods: CAC was quantified using a Siemens Cardiac 64 scanner, and vitamin D levels and the presence of traditional and novel risk factors for CAD were obtained in 846 HIV-infected African American (AA) participants aged 25 years or older in Baltimore, MD, USA without symptoms or clinical evidence of CAD. Results: The prevalence of vitamin D deficiency (25-hydroxy vitamin D

Weiwei Tong1,2, Xueyan Cao2, Shihui Wen2, Rui Guo2, Mingwu Shen2, Jianhua Wang3, Xiangyang Shi1,2,41State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, 2College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 3Department of Biochemistry and Molecular Cell Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China; 4Centro de Química da Madeira, Universidade da Madeira, Funchal, PortugalAbstract: There is a general necessity to improve the specificity and efficiency of the polymerase chain reaction (PCR), and exploring the PCR-enhancing mechanism still remains a great challenge. In this paper we report the use of branched polyethyleneimine (PEI)-based derivatives and hybrid nanocomposites as a novel class of enhancers to improve the specificity and efficiency of a nonspecific PCR system. We show that the surface-charge polarity of PEI and PEI derivatives plays a major role in their effectiveness to enhance the PCR. Positively charged amine-terminated pristine PEI, partially (50%) acetylated PEI (PEI-Ac50), and completely acetylated PEI (PEI-Ac) are able to improve PCR efficiency and specificity with an optimum concentration order of PEI < PEI-Ac50 < PEI-Ac, whereas negatively charged carboxyl-terminated PEI (PEI-SAH; SAH denotes succinamic acid groups) and neutralized PEI modified with both polyethylene glycol (PEG) and acetyl (Ac) groups (PEI-PEG-Ac) are unable to improve PCR specificity and efficiency even at concentrations three orders of magnitude higher than that of PEI. Our data clearly suggests that the PCR-enhancing effect is primarily based on the interaction between the PCR components and the PEI derivatives, where electrostatic interaction plays a major role in concentrating the PCR components locally on the backbones of the branched PEI. In addition, multiwalled carbon nanotubes modified with PEI and PEI-stabilized gold nanoparticles are also able to improve the PCR specificity and efficiency with an optimum PEI concentration less than that of the PEI alone, indicating that the inorganic component of the nanocomposites may help improve the interaction between PEI and the PCR components. The developed PEI-based derivatives or nanocomposites may be used as efficient additives to enhance other PCR systems for different biomedical applications.Keywords: polyethyleneimine, gold nanoparticles, multiwalled carbon nanotubes, nanocomposites, polymerase chain reaction, specificity, efficiency

Abstract Background The completion of the sequencing of human, mouse and rat genomes and knowledge of cross-species gene homologies enables studies of differential gene expression in animal models. These types of studies have the potential to greatly enhance our understanding of diseases such as liver cancer in humans. Genes co-expressed across multiple species are most likely to have conserved functions. We have used various bioinformatics approaches to examine microarray expression profiles from liver neoplasms that arise in albumin-SV40 transgenic rats to elucidate genes, chromosome aberrations and pathways that might be associated with human liver cancer. Results In this study, we first identified 2223 differentially expressed genes by comparing gene expression profiles for two control, two adenoma and two carcinoma samples using an F-test. These genes were subsequently mapped to the rat chromosomes using a novel visualization tool, the Chromosome Plot. Using the same plot, we further mapped the significant genes to orthologous chromosomal locations in human and mouse. Many genes expressed in rat 1q that are amplified in rat liver cancer map to the human chromosomes 10, 11 and 19 and to the mouse chromosomes 7, 17 and 19, which have been implicated in studies of human and mouse liver cancer. Using Comparative Genomics Microarray Analysis (CGMA), we identified regions of potential aberrations in human. Lastly, a pathway analysis was conducted to predict altered human pathways based on statistical analysis and extrapolation from the rat data. All of the identified pathways have been known to be important in the etiology of human liver cancer, including cell cycle control, cell growth and differentiation, apoptosis, transcriptional regulation, and protein metabolism. Conclusion The study demonstrates that the hepatic gene expression profiles from the albumin-SV40 transgenic rat model revealed genes, pathways and chromosome alterations consistent with experimental and clinical research in human liver cancer. The bioinformatics tools presented in this paper are essential for cross species extrapolation and mapping of microarray data, its analysis and interpretation.