Publications by authors named "Renwen Zhang"

44 Publications

Effect of Osteoporosis on Adjacent Segmental Degeneration After Posterior Lumbar Interbody Fusion Under Whole Body Vibration.

World Neurosurg 2021 Jun 12. Epub 2021 Jun 12.

School of Chinese Medicine, Jinan University, Guangzhou, China. Electronic address:

Background: Adjacent segmental degeneration (ASD) is one of the common complications after posterior lumbar interbody fusion (PLIF). Both whole body vibration (WBV) and osteoporosis are important factors associated with the biomechanics of the lumbar spine. However, to the best of our knowledge, no studies have investigated the effects of osteoporosis on ASD after PLIF under WBV.

Methods: In the present study, using one normal model, one PLIF model and one PLIF with osteoporosis model of the L1-S1 segment were developed. A 5-Hz, 40-N sinusoidal vertical load was imposed on the superior surface of L1 of each model to simulate WBV, and the dynamic responses and maximal values of intradiscal pressure, shear stress on annulus fibrosus, total deformation, and disc bulge were evaluated in the L1-L2, L2-L3, L3-L4, and L5-S1 segments.

Results: At the L1-L2, L2-L3, and L3-L4 levels, the differences in the dynamic responses and maximal values in intradiscal pressure, shear stress, total deformation, and disc bulge between the PLIF and PLIF with osteoporosis models were slight. However, at the L5-S1 level, the dynamic response curves and maximal intradiscal pressure, shear stress, and disc bulge values in the PLIF with osteoporosis model were significantly lower than those in the PLIF model.

Conclusions: Osteoporosis can mitigate the development of ASD in the lower adjacent segment but has no obvious influence on the upper adjacent segments during WBV.
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http://dx.doi.org/10.1016/j.wneu.2021.06.031DOI Listing
June 2021

Linking Network Characteristics of Online Social Networks to Individual Health: A Systematic Review of Literature.

Health Commun 2020 Jun 17:1-11. Epub 2020 Jun 17.

Department of Communication, School of Communication and Information, Rutgers, The State University of New Jersey.

Social networks have long been viewed as a structural determinant of health. With the proliferation of digital technologies, numerous studies have examined the health implications of online social networks (OSNs). However, the mechanisms through which OSNs may influence individual health are poorly understood. Employing a social network approach, this paper presents a systematic review of the literature examining how network characteristics of OSNs are linked to individuals' health behavior and/or status. Drawing on keyword searches in nine databases, we identified and analyzed 22 relevant articles from 1,705 articles published prior to 2017. The findings show that individual health is associated with a number of network characteristics, including both individual-level attributes (e.g., centrality) and network-level attributes (e.g., density, clustering). All of the included studies ( = 22) have focused on egocentric networks, and nine studies also collected whole network data of online health communities. Based on our review, we highlight three fruitful areas in the application of OSNs in public health: (1) disease and risk detection, (2) disease prevention and intervention, and (3) health behavior change. However, the precise mechanisms and causal pathways through which OSNs affect health remain unclear. More theoretically grounded, longitudinal, and mixed methods research is needed to advance this line of research.
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http://dx.doi.org/10.1080/10410236.2020.1773703DOI Listing
June 2020

Biomechanical effects of osteoporosis on adjacent segments after posterior lumbar interbody fusion: A finite element study.

Pak J Med Sci 2021 Mar-Apr;37(2):403-408

Shujie Tang, School of Chinese Medicine, Jinan University, Guangzhou, 510630, China.

Objective: To investigate the biomechanical effects of osteoporosis on adjacent segments after posterior lumbar interbody fusion (PLIF).

Methods: This study was designed and conducted in the Traumatology and Orthopedics Laboratory, School of Chinese Medicine, Jinan University, Guangzhou, China, between December 2019 and February 2020. A healthy finite element model of L3-S1 was developed along with one PLIF model and one PLIF with osteoporosis model. Based on a hybrid test method, the inferior surface of S1 was entirely fixed, and a preload of 400N combined with an adjusted moment was imposed on the superior surface of L3 in each model to simulate flexion, extension, lateral bending and axial rotation. The intradiscal pressure (IDP), shear stress on annulus fibrosus, and the range of motion (ROM) of L3-L4 and L5-S1 were calculated and compared.

Results: In each direction, the highest value of IDP and shear stress on annulus fibrosus at L3-L4 and L5-S1 was found in the PLIF model, and the lowest value in the healthy model. The largest ROM at L4-L5 appeared in the healthy model, and the smallest value in the PLIF model in each direction. At L3-L4 and L5-S1, the highest ROM in most directions was found in the PLIF model, followed by the PLIF with osteoporosis model, and the lowest value in the healthy model.

Conclusions: Osteoporosis can decrease IDP, shear stress on annulus fibrosus, and ROM at adjacent levels, and slow down the development of ASD after PLIF.
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http://dx.doi.org/10.12669/pjms.37.2.3223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931299PMC
March 2021

"Energy is a Finite Resource": Designing Technology to Support Individuals across Fluctuating Symptoms of Depression.

Proc SIGCHI Conf Hum Factor Comput Syst 2020 Apr;2020

Northwestern University Chicago, IL, USA.

While the HCI field increasingly examines how digital tools can support individuals in managing mental health conditions, it remains unclear how these tools can accommodate these conditions' temporal aspects. Based on weekly interviews with five individuals with depression, conducted over six weeks, this study identifies design opportunities and challenges related to extending technology-based support across fluctuating symptoms. Our findings suggest that participants perceive events and contexts in daily life to have marked impact on their symptoms. Results also illustrate that ebbs and flows in symptoms profoundly affect how individuals practice depression self-management. While digital tools often aim to reach individuals while they feel depressed, we suggest they should also engage individuals when they are less symptomatic, leveraging their energy and motivation to build habits, establish plans and goals, and generate and organize content to prepare for symptom onset.
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http://dx.doi.org/10.1145/3313831.3376309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877799PMC
April 2020

Does Osteoporosis Affect the Adjacent Segments Following Anterior Lumbar Interbody Fusion? A Finite Element Study.

World Neurosurg 2021 02 7;146:e739-e746. Epub 2020 Nov 7.

School of Chinese Medicine, Jinan University, Guangzhou, China. Electronic address:

Background: Adjacent segment degeneration is a common complication following anterior lumbar interbody fusion (ALIF). Osteoporosis is becoming increasingly prevalent in the elderly population and thus patients undergoing ALIF may experience osteoporosis with age. However, the influence of osteoporosis on adjacent segment degeneration after ALIF remains unclear.

Methods: Three finite element models of the L3-S1 segment, including a healthy model, an ALIF model, and an ALIF with osteoporosis model, were used for analysis. ALIF was simulated at the L4-L5 segment. Based on a hybrid test method, the models were imposed with a preload of 400 N and an adjusted moment in flexion, extension, lateral bending, and axial torsion. Intradiscal pressure, shear stress on anulus fibrosus, and range of motion at L3-L4 and L5-S1 were calculated and compared.

Results: In each direction, the maximal values of intradiscal pressure and shear stress on anulus fibrosus at L3-L4 and L5-S1 were found in the ALIF model, and the minimal values were found in the healthy model. At L3-L4 and L5-S1, the maximal values of range of motion in most directions were found in the ALIF model followed by the ALIF with osteoporosis model, and the minimal values were found in the healthy model. However, the maximal value of range of motion at L5-S1 in axial torsion was found in the ALIF with osteoporosis model.

Conclusions: Osteoporosis may mitigate the adverse influence of ALIF on adjacent segments.
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http://dx.doi.org/10.1016/j.wneu.2020.11.005DOI Listing
February 2021

Identifying Practice Facilitation Delays and Barriers in Primary Care Quality Improvement

J Am Board Fam Med 2020 Sep-Oct;33(5):655-664

From the Feinberg School of Medicine, Northwestern University, Chicago, IL (JY, AAW); Center for Health Information Partnerships (CHiP), Institute of Public Health & Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (JY, JEB, TLW, ANK); Department of Communication Studies, Northwestern University, Evanston, IL (RZ); Division of Health and Biomedical Informatics, Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University Chicago, IL (ANK, NDS); Division of General Internal Medicine and Geriatrics, Department of Medicine, Feinberg School of Medicine, Northwestern University Chicago, IL (TLW, ANK).

Objective: Practice facilitation is an effective approach to implementing quality improvement (QI) interventions in practice-based research networks (PBRNs). Regular facilitator-practice interactions are necessary for successful facilitation, and missed engagements may hinder the process of practice improvement. This study employs a mixed-methods approach to characterize the dynamics of practice facilitation and examine facilitation delays and barriers, as well as their association with the achievement of QI program goals in a PBRN initiative.

Methods: This study presents a secondary analysis of data from 226 primary care practices that participated in the Healthy Hearts in the Heartland (H3) initiative. We performed a time series analysis to identify delays in facilitation activities, and then qualitatively analyzed practice facilitators' notes (n = 4358) to uncover facilitation barriers. Finally, we assessed the relationship between delays, barriers, and QI intervention completion.

Results: While most facilitation activities occurred at regular, practice-specific tempos, nearly all practices experienced at least 1 delay. Practices with more delays had lower QI intervention completion rates. Practices with more delays were more likely to have encountered barriers such as lack of time and staff, lack of staff engagement, technical issues, and staff turnover.

Discussion And Conclusion: This study is the first to quantify irregular intervals between facilitation activities and demonstrate their negative association with project completion. The analytic method can be applied to identify at-risk practices and to accelerate timely interventions in future studies. Our delay detection algorithm could inform the design of a decision support system that notifies facilitators which practices may benefit from timely attention and resources.
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http://dx.doi.org/10.3122/jabfm.2020.05.200058DOI Listing
July 2021

Biomechanical Comparison of Lumbar Fixed-Point Oblique Pulling Manipulation and Traditional Oblique Pulling Manipulation in Treating Lumbar Intervertebral Disk Protrusion.

J Manipulative Physiol Ther 2020 06 20;43(5):446-456. Epub 2020 Aug 20.

College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong Province, China.

Objective: To compare the biomechanical effect of lumbar fixed-point oblique pulling manipulation and traditional oblique pulling manipulation in the treatment of protrusion of lumbar intervertebral disk, and investigate the influence of disk degeneration on the 2 manipulations.

Methods: Three finite element models including 1 normal model, 1 mild degeneration, and 1 moderate degeneration model of L3-S1 were developed to simulate 2 oblique pulling manipulations. The disk protrusion was assumed to be in the left central and subarticular zone of the L4-L5 disk, and manipulations were carried out on the right. A 15-Nm right axial rotation moment and 150-N compressive loading were imposed on the upper endplate of L3 to simulate a traditional oblique pulling manipulation. To simulate lumbar fixed-point oblique pulling manipulation, in addition to a 15-Nm moment and 150-N compressive loading imposed on the L3 upper endplate, a 50-N force was imposed on the right lateral area of the L4 spinous process in a left front direction. The displacement and stress in the left central and subarticular zone of the L4-L5 disk were calculated and compared in the 3 models.

Results: The average displacement and stress in the left central and subarticular zone of L4-L5 disk were higher in fixed-point oblique pulling manipulation than those in traditional oblique pulling manipulation (P < .05). In addition, the values of average stress and displacement decreased significantly with the increase of lumbar disk degeneration (P < .05).

Conclusion: Lumbar fixed-point oblique pulling manipulation showed a better biomechanical effect than traditional oblique pulling manipulation, and lumbar disk degeneration affected the 2 manipulations adversely in the virtual treatment of protrusion of the lumbar intervertebral disk using finite element models.
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http://dx.doi.org/10.1016/j.jmpt.2019.10.004DOI Listing
June 2020

Designing Mental Health Technologies that Support the Social Ecosystem of College Students.

Proc SIGCHI Conf Hum Factor Comput Syst 2020 Apr;2020

Communication Studies, Northwestern University, Evanston, IL, United States.

The last decade has seen increased reports of mental health problems among college students, with college counseling centers struggling to keep up with the demand for services. Digital mental health tools offer a potential solution to expand the reach of mental health services for college students. In this paper, we present findings from a series of design activities conducted with college students and counseling center staff aimed at identifying needs and preferences for digital mental health tools. Results emphasize the social ecosystems and social support networks in a college student's life. Our findings highlight the predominant role of known peers, and the ancillary roles of unknown peers and non-peers (e.g., faculty, family) in influencing the types of digital mental health tools students desire, and the ways in which they want to learn about mental health tools. We identify considerations for designing digital mental health tools for college students that take into account the identified social factors and roles.
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http://dx.doi.org/10.1145/3313831.3376362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351354PMC
April 2020

MicroRNA-574-5p in gastric cancer cells promotes angiogenesis by targeting protein tyrosine phosphatase non-receptor type 3 (PTPN3).

Gene 2020 Apr 20;733:144383. Epub 2020 Jan 20.

Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun 130021, Jilin Province, China. Electronic address:

We elucidate in this study that up-regulation of miR-574-5p in gastric cancer cells under hypoxic conditions contributed to angiogenesis. We found that miR-574-5p and HIF-1α were up-regulated in gastric cancer cells cultured under 2% O or in medium containing CoCl and in muscle tissues of mice injected with NaNO, indicating up-regulation of miR-574-5p in vitro or in vivo in response to hypoxic conditions. We hypothesized that up-regulation of miR-574-5p could promote angiogenesis. Transfection of gastric cancer cells with miR-574-5p mimics or inhibitor resulted in increase or decrease in the expression of VEGFA. Viability, migration, invasion and tube formation of HUVECs cultured with conditioned medium from SGC/574 cells transfected with miR-574-5p inhibitor were reduced. Tube formation of HUVECs cultured with conditioned medium from SGC-7901 cells transfected with miR-574-5p mimics was increased. An in vivo study demonstrated that inhibition of miR-574-5p in the tumor xenografts of mice reduced the expression of CD31 one of the endothelial cell markers. We identified PTPN3 a tyrosine phosphatase as a target of miR-574-5p that bound to the 3'UTR of PTPN3 mRNA to inhibit the expression of PTPN3. Furthermore, the data in this study demonstrated that inhibition of PTPN3 in gastric cancer cells enhanced phosphorylation of p44/42 MAPKs and promoted angiogenesis. We conclude that miR-574-5p in gastric cancer cells promoted angiogenesis via enhancing phosphorylation of p44/42 MAPKs by miR-574-5p inhibition of PTPN3 expression.
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http://dx.doi.org/10.1016/j.gene.2020.144383DOI Listing
April 2020

Clinically Meaningful Use of Mental Health Apps and its Effects on Depression: Mixed Methods Study.

J Med Internet Res 2019 12 20;21(12):e15644. Epub 2019 Dec 20.

Center for Behavioral Intervention Technologies, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

Background: User engagement is key to the effectiveness of digital mental health interventions. Considerable research has examined the clinical outcomes of overall engagement with mental health apps (eg, frequency and duration of app use). However, few studies have examined how specific app use behaviors can drive change in outcomes. Understanding the clinical outcomes of more nuanced app use could inform the design of mental health apps that are more clinically effective to users.

Objective: This study aimed to classify user behaviors in a suite of mental health apps and examine how different types of app use are related to depression and anxiety outcomes. We also compare the clinical outcomes of specific types of app use with those of generic app use (ie, intensity and duration of app use) to understand what aspects of app use may drive symptom improvement.

Methods: We conducted a secondary analysis of system use data from an 8-week randomized trial of a suite of 13 mental health apps. We categorized app use behaviors through a mixed methods analysis combining qualitative content analysis and principal component analysis. Regression analyses were used to assess the association between app use and levels of depression and anxiety at the end of treatment.

Results: A total of 3 distinct clusters of app use behaviors were identified: learning, goal setting, and self-tracking. Each specific behavior had varied effects on outcomes. Participants who engaged in self-tracking experienced reduced depression symptoms, and those who engaged with learning and goal setting at a moderate level (ie, not too much or not too little) also had an improvement in depression. Notably, the combination of these 3 types of behaviors, what we termed "clinically meaningful use," accounted for roughly the same amount of variance as explained by the overall intensity of app use (ie, total number of app use sessions). This suggests that our categorization of app use behaviors succeeded in capturing app use associated with better outcomes. However, anxiety outcomes were neither associated with specific behaviors nor generic app use.

Conclusions: This study presents the first granular examination of user interactions with mental health apps and their effects on mental health outcomes. It has important implications for the design of mobile health interventions that aim to achieve greater user engagement and improved clinical efficacy.
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http://dx.doi.org/10.2196/15644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942194PMC
December 2019

Histone H2A-peptide-hybrided upconversion mesoporous silica nanoparticles for bortezomib/p53 delivery and apoptosis induction.

Colloids Surf B Biointerfaces 2020 Feb 28;186:110674. Epub 2019 Nov 28.

College of Biology & Food Engineering, Jilin Institute of Chemical Technology, Jilin, Jilin, 132022, PR China. Electronic address:

The design and development of advanced gene/drug codelivery nanocarrier with good biocompatibility for cancer gene therapy is desirable. Herein, we reported a gene delivery nanoplatform to synergized bortezomib (BTZ) for cancer treatment with histone H2A-hybrided, upconversion luminescence (UCL)-guided mesoporous silica nanoparticles [UCNPs(BTZ)@mSiO-H2A]. The functionalization of H2A on the surface of UCNPs(BTZ)@mSiO nanoparticles realized the improvement of biocompatibility and enhancement of gene encapsulation and transfection efficiency. More importantly, then UCNPs(BTZ)@mSiO-H2A/p53 induced specific and efficient apoptotic cell death in p53-null cancer cells and restored the functional activity of tumor suppressor p53 by the success of co-delivery of BTZ/p53. Moreover, the transfection with UCNPs(BTZ)@mSiO-H2A/p53 in p53-deficient non-small cell lung cancer cells changed the status of p53 and substantially enhanced the p53-mediated sensitivity of encapsulated BTZ inside the UCNPs(BTZ)@mSiO/p53. Meanwhile, core-shell structured mesoporous silica nanoparticles [email protected] as an UCL agent can detect the real-time interaction of nanoparticles with cells and uptake/penetration processes. The results here suggested that the as-developed UCNPs(BTZ)@mSiO-H2A/p53 nanoplatform with coordinating biocompatibility, UCL image, and sustained release manner might be desirable gene/drug codelivery nanocarrier for clinical cancer therapy.
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http://dx.doi.org/10.1016/j.colsurfb.2019.110674DOI Listing
February 2020

Comparisons of the Effectiveness and Safety of Tuina, Acupuncture, Traction, and Chinese Herbs for Lumbar Disc Herniation: A Systematic Review and Network Meta-Analysis.

Evid Based Complement Alternat Med 2019 20;2019:6821310. Epub 2019 Mar 20.

School of Chinese Medicine, Jinan University, Guangzhou, Guangdong Province 510632, China.

Background: Tuina, acupuncture, traction, and Chinese herbs play an important role in the treatment of lumbar disc herniation. However, the comparative effectiveness and safety of the four commonly utilized treatment modalities are still unclear.

Objective: To compare the effectiveness and safety of the four interventions for lumbar disc herniation.

Methods: Randomized controlled trials comparing any two of the four interventions in the treatment of lumbar disc herniation were identified using the following databases: PubMed, the Cochrane Library, Embase, Web of Science, the China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and Wanfang data, and network meta-analysis was performed using STATA 14.0.

Results: One hundred and twenty-one studies involving a total of 13075 patients were included. In all the outcome measurements, traction demonstrated a worst effectiveness, and Tuina and acupuncture demonstrated a best effectiveness, but no significant differences were found between Tuina and acupuncture. Compared with Tuina or acupuncture, Chinese herbs showed a similar effectiveness in Visual Analogue Score and Japanese Orthopedic Association Scores, but an inferior effectiveness in invalid rate and cure rate.

Conclusions: In the treatment of lumbar disc herniation, Tuina and acupuncture were superior to traction or Chinese herbs, and the effectiveness of traction was the worst. However, considering the limitations of this review, more high-quality trials, especially those comparing Chinese herbs with the other three interventions, should be carried out in the future to further confirm the current findings.
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http://dx.doi.org/10.1155/2019/6821310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446119PMC
March 2019

Provider perspectives on the integration of patient-reported outcomes in an electronic health record.

JAMIA Open 2019 Apr 30;2(1):73-80. Epub 2019 Jan 30.

Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

Objective: Integrating patient-reported outcomes (PROs) into electronic health records (EHRs) can improve patient-provider communication and delivery of care. However, new system implementation in health-care institutions is often accompanied by a change in clinical workflow and organizational culture. This study examines how well an EHR-integrated PRO system fits clinical workflows and individual needs of different provider groups within 2 clinics.

Materials And Methods: Northwestern Medicine developed and implemented an EHR-integrated PRO system within the orthopedics and oncology departments. We conducted interviews with 11 providers who had interacted with the system. Through thematic analysis, we synthesized themes regarding provider perspectives on clinical workflow, individual needs, and system features.

Results: Our findings show that EHR-integrated PROs facilitate targeted conversation with patients and automated triage for psychosocial care. However, physicians, psychosocial providers, and medical assistants faced different challenges in their use of the PRO system. Barriers mainly stemmed from a lack of actionable data, workflow disruption, technical issues, and a lack of incentives.

Discussion: This study sheds light on the ecosystem around EHR-integrated PRO systems (such as user needs and organizational factors). We present recommendations to address challenges facing PRO implementation, such as optimizing data collection and auto-referral processes, improving data visualizations, designing effective educational materials, and prioritizing the primary user group.

Conclusion: PRO integration into routine care can be beneficial but also require effective technology design and workflow configuration to reach full potential use. This study provides insights into how patient-generated health data can be better integrated into clinical practice and care delivery processes.
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http://dx.doi.org/10.1093/jamiaopen/ooz001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447042PMC
April 2019

MicroRNA-574-3p regulates epithelial mesenchymal transition and cisplatin resistance via targeting ZEB1 in human gastric carcinoma cells.

Gene 2019 Jun 24;700:110-119. Epub 2019 Mar 24.

Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun 130021, Jilin Province, China. Electronic address:

MicroRNA-574-3p (miR-574-3p) has different roles in different cancer types. However, the exact regulation mechanism of miR-574-3p in gastric cancer (GC) progression remains unclear. Thus, we aimed to evaluate the role of miR-574-3p in GC metastasis. We investigated the mechanism via which miR-574-3p regulated cancer cell migration and invasion to determine the relationship between epithelial mesenchymal transition (EMT) and drug resistance. Our results indicated that human GC cell line SGC7901 cells were more sensitive to cisplatin (DDP), but SGC7901 cisplatin-resistant cells (SGC7901/DDP) were more resistant to DDP and had mesenchymal characteristics. In addition, miR-574-3p overexpression up-regulated E-cadherin expression, and concomitantly down-regulated the expression of vimentin. We also identified zinc finger E-box binding homeobox transcription factor 1 (ZEB1), a crucial EMT inducer gene, as a new target of miR-574-3p. In fact, miR-574-3p bound the 3' untranslated region (3'-UTR) of ZEB1, regulating expression of this transcription factor at both the mRNA and protein levels. Furthermore, miR-574-3p overexpression reduced the migratory and invasive properties of the SGC7901/DDP cells and inhibited cisplatin (DDP) resistance in vitro and in vivo. In conclusion, the results indicated that miR-574-3p inhibited the EMT and enhanced cisplatin sensitivity in GC cells by suppressing ZEB1. These results provide further evidence for the critical roles of miR-574-3p and ZEB1 in invasion and migration regulation characteristics of GC cells.
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http://dx.doi.org/10.1016/j.gene.2019.03.043DOI Listing
June 2019

CD8 T cell-derived perforin aggravates secondary spinal cord injury through destroying the blood-spinal cord barrier.

Biochem Biophys Res Commun 2019 04 18;512(2):367-372. Epub 2019 Mar 18.

Department of Orthopedics, First Affiliated Hospital of Jinan University, 613 West Huangpu RD, Guangzhou, 510632, China. Electronic address:

Perforin plays an important role in autoimmune and infectious diseases, but its function in immune inflammatory responses after spinal cord injury (SCI) has received insufficient attention. The goal of this study is to determine the influence of perforin after spinal cord injury (SCI) on secondary inflammation. Compared recovery from SCI in perforin knockout (Prf1) and wild-type(WT)mice, WT mice had significantly lower the Basso mouse score (BMS), CatWalk XT, and motor-evoked potentials (MEPs) than Prf1 mice. Spinal cord lesions were also more obvious through glial fibrillary acidic protein (GFAP), Nissl, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. Furthermore, the blood-spinal cord barrier (BSCB) disruption was more severe and inflammatory cytokine levels were higher. Flow cytometry indicated that perforin mainly originated from CD8 T cells. With flow cytometry and enzyme-linked immunosorbent assay (ELISA), human cerebrospinal fluid (CSF) yielded similar results. Together, this study firstly demonstrated that CD8 T cell-derived perforin is detrimental to SCI recovery in the mouse model. Mechanistically, this effect occurs because perforin increases BSCB permeability, causing inflammatory cells and related cytokines to infiltrate and disrupt the nervous system.
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http://dx.doi.org/10.1016/j.bbrc.2019.03.002DOI Listing
April 2019

Synthesis and Characterization of a Silica-Based Drug Delivery System for Spinal Cord Injury Therapy.

Nanomicro Lett 2019 Mar 11;11(1):23. Epub 2019 Mar 11.

College of Chemistry and Material Sciences, Jinan University, Guangzhou, 510632, People's Republic of China.

Acute inflammation is a central component in the progression of spinal cord injury (SCI). Anti-inflammatory drugs used in the clinic are often administered systemically at high doses, which can paradoxically increase inflammation and result in drug toxicity. A cluster-like mesoporous silica/arctigenin/CAQK composite ([email protected]) drug delivery system was designed to avoid systemic side effects of high-dose therapy by enabling site-specific drug delivery to the spinal cord. In this nanosystem, mesoporous silica was modified with the FITC fluorescent molecule and CAQK peptides that target brain injury and SCI sites. The size of the nanocarrier was kept at approximately 100 nm to enable penetration of the blood-brain barrier. Arctigenin, a Chinese herbal medicine, was loaded into the nanosystem to reduce inflammation. The in vivo results showed that [email protected] could attenuate inflammation at the injury site. Behavior and morphology experiments suggested that [email protected] could diminish local microenvironment damage, especially reducing the expression of interleukin-17 (IL-17) and IL-17-related inflammatory factors, inhibiting the activation of astrocytes, thus protecting neurons and accelerating the recovery of SCI. Our study demonstrated that this novel, silica-based drug delivery system has promising potential for clinical application in SCI therapy.
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http://dx.doi.org/10.1007/s40820-019-0252-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770885PMC
March 2019

Comparison of three fixation modalities for unilateral open-door cervical laminoplasty: a systematic review and network meta-analysis.

Neurosurg Rev 2020 Jun 27;43(3):813-823. Epub 2018 Sep 27.

School of Chinese Medicine, Jinan University, 601 Huangpu Dadao Road, Guangzhou, 510632, Guangdong Province, China.

Three fixation modalities including suture suspensory, anchor, and titanium plate are used extensively in unilateral open-door cervical laminoplasty. Nevertheless, up to now no systematic review and network meta-analysis have been published, and the differences in efficacy and safety of the three fixation modalities are still unclear. The purpose of this study is to compare the effectiveness and safety of the three fixation modalities including suture suspensory, anchor, and titanium plate in unilateral open-door cervical laminoplasty. Randomized controlled trials and cohort studies which compared the three interventions in unilateral open-door cervical laminoplasty were identified using the following databases: PubMed, Cochrane Library, Embase, Web of science, China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and Wanfang data. Network meta-analysis was performed using R 3.4.3 software and STATA version 14.0. The results revealed that compared with suture suspensory, titanium plate and anchor showed the same effects in Japanese Orthopedic Association Scores, operative time, and blood loss. However, titanium plate showed superiority in postoperative range of motion of cervical spine, incidence of axial symptoms, and C5 paralysis; in terms of cervical curvature, titanium plate also showed better effectiveness than suture suspensory, but similar as anchor. Our network meta-analysis suggests that titanium plate is preferable to suture suspensory or anchor with more range of motion and lower incidence of axial symptoms and C5 paralysis. However, considering the limitations of this research, high-quality trials are needed in the future to evaluate the outcomes.
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http://dx.doi.org/10.1007/s10143-018-1035-0DOI Listing
June 2020

Exercise therapy versus surgery for lumbar spinal stenosis: A systematic review and meta-analysis.

Pak J Med Sci 2018 Jul-Aug;34(4):879-885

Shujie Tang, School of Chinese Medicine, Jinan University, Guangzhou, Guangdong Province, 510632, China.

Objective: To compare the effectiveness of exercise therapy with surgery for lumbar spinal stenosis.

Methods: Five English databases PubMed, the Cochrane Library, Web of science, OVID and PEDro database were searched for randomized controlled trials comparing surgical procedures with exercise therapy for lumbar spinal stenosis. Information on patients, study design, inclusion criteria, intervention and follow-up, outcomes, treatment details and adverse events were extracted. Meta-analysis was performed using Review Manager Version 5.3.

Results: Two randomized controlled trials and one mixed design trial with a total of 897 patients were included. The pooled results showed a significant difference between exercise and surgery in Oswestry Disability Index at two years (MD= 3.85, 95%CI: 0.48 to 7.22; P=0.03), but no significant difference at six months (MD= 2.18, 95%CI: -2.80 to 7.17; P=0.39) and one year (MD= 4.26, 95%CI: -1.79 to 10.32; P=0.17). In terms of physical function of 36 Items Short Form Health Survey, there were no significant differences between exercise and surgery at six months (MD= -2.23, 95% CI: -7.46 to 2.99; P=0.40), one year (MD= -2.17, 95% CI: -7.44 to 3.10; P=0.42) and two years (MD= -0.67, 95% CI: -6.16 to 4.82; P=0.81).

Conclusion: In brief, the current evidence demonstrated a trend that exercise therapy had a similar effect for lumbar spinal stenosis compared with decompressive laminectomies. However, for the small sample size and low methodology quality of the included trials, some rigorously designed and large-scaled RCTs need to be performed to confirm the conclusion.
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http://dx.doi.org/10.12669/pjms.344.14349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115590PMC
September 2018

Comparative effectiveness and safety of posterior lumbar interbody fusion, Coflex, Wallis, and X-stop for lumbar degenerative diseases: A systematic review and network meta-analysis.

Clin Neurol Neurosurg 2018 09 30;172:74-81. Epub 2018 Jun 30.

School of Chinese Medicine, Jinan University, Guangzhou, Guangdong province, 510632, China. Electronic address:

Posterior lumbar interbody fusion and lumbar interspinous non-fusion technique are common surgical procedures for lumbar degenerative diseases, but the effectiveness and safety of these two techniques are still unclear. We performed this network meta-analysis to evaluate the comparative effectiveness and safety of posterior lumbar interbody fusion and the three commonly used interspinous devices including Coflex, Wallis, and X-stop for lumbar degenerative diseases. Randomized controlled trials and cohort studies comparing among posterior lumbar interbody fusion, Coflex, Wallis, and X-stop for lumbar degenerative diseases were identified using the databases including PubMed, the Cochrane Library, Web of Science, the China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and Wanfang data. A network meta-analysis was performed using R 3.4.3 software. 27 studies with 2241 patients were included. The results of network meta-analysis revealed that no significant differences in Oswestry Disability Index, Visual Analogue Scale, Japanese Orthopedic Association Scores, and posterior disc height were found among posterior lumbar interbody fusion group, Coflex, Wallis, or X-stop. However, compared with posterior lumbar interbody fusion, the three interspinous process devices presented with significantly more range of motion in surgical segment, but no significant difference was found among these three interspinous process devices. Node-splitting analysis showed no significant inconsistency in our network meta-analysis. We concluded that compared with posterior lumbar interbody fusion, Coflex, Wallis and X-stop had the same effectiveness in relieving pain, improving quality of life, recovering disc space height and lumbar function, but may lower incidence of adjacent segment degeneration.
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http://dx.doi.org/10.1016/j.clineuro.2018.06.030DOI Listing
September 2018

hucMSC derived exosomes promote functional recovery in spinal cord injury mice via attenuating inflammation.

Mater Sci Eng C Mater Biol Appl 2018 Aug 10;89:194-204. Epub 2018 Apr 10.

The First Affiliated Hospital, Biomedical Translational Research Institute and Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Jinan University, Guangzhou 510632, PR China. Electronic address:

The exploration of effective spinal cord injury (SCI) healing still remain a great challenge due to the high morbidity, complex pathology and unclear targets. Human umbilical cord mesenchymal stem cells (hucMSC) play an important role in tissue regeneration. However, transplanting stem cells has a potential risk of teratogenicity. Recent studies have suggested that exosomes secreted by stem cells may contribute to tissue injury repair. We hypothesized that the application of hucMSC derived exosomes may be a potential way for SCI treatment. Our studies showed the hucMSC derived exosomes with a mean particle size of 70 nm could effectively trigger the bone marrow derived macrophage (BMDM) polarization from M1 to a M2 phenotype. In vivo studies demonstrated that the hucMSC derived exosomes could improve the functional recovery after SCI through down-regulation of the inflammatory cytokines, such as TNF-α, MIP-1α, IL-6 and IFN-γ. Collectively, our findings indicated that hucMSC derived exosomes could facilitate spinal cord injury healing via attenuating the inflammation of the injury region. Our results provided a new perspective and therapeutic strategy for the use of hucMSC derived exosomes in soft tissue repair.
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http://dx.doi.org/10.1016/j.msec.2018.04.006DOI Listing
August 2018

Acupuncture for lumbar disc herniation: a systematic review and meta-analysis.

Acupunct Med 2018 04 1;36(2):62-70. Epub 2018 Mar 1.

College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong, China.

Objective: To evaluate evidence for the effectiveness of acupuncture in the treatment of lumbar disc herniation (LDH).

Methods: Electronic databases were searched to identify randomised controlled trials (RCTs) of acupuncture for LDH. A meta-analysis was conducted using RevMan 5.3 and the evidence level was assessed using GRADE methodology.

Results: Thirty RCTs involving 3503 participants were included in the study. Meta-analysis showed that acupuncture had a higher total effective rate than lumbar traction (RR=1.1, 95% CI 1.05 to 1.15; p<0.001), ibuprofen (RR=1.24, 95% CI 1.03 to 1.48; p=0.02), diclofenac sodium (RR=1.44, 95% CI 1.24 to 1.67; p<0.001) and meloxicam (RR=1.16, 95% CI 1.03 to 1.31; p=0.01). Acupuncture was also better than lumbar traction (SMD -1.33, 95% CI -1.82 to -0.84; p<0.001) and diclofenac sodium (SMD -1.36, 95% CI -2.59 to -0.13; p=0.03) in terms of visual analogue scale (VAS) scores, and better than lumbar traction (SMD 0.96, 95% CI 0.48 to 1.45; p=0.0001) with respect to Japanese Orthopaedic Association (JOA) scores. In addition, the total effective rate in five individual trials was greater for acupuncture than for mannitol plus dexamethasone and mecobalamin, ibuprofen plus fugui gutong capsule, loxoprofen, mannitol plus dexamethasone and huoxue zhitong decoction, respectively. Additionally, two individual trials showed a superior effect of acupuncture in VAS scores comparedwith ibuprofen or mannitol plus dexamethasone, respectively.

Conclusions: Acupuncture showed a more favourable effect in the treatment of LDH than lumbar traction, ibuprofen, diclofenac sodium, meloxicam, mannitol plus dexamethasone and mecobalamin, fugui gutong capsule plus ibuprofen, mannitol plus dexamethasone, loxoprofen and huoxue zhitong decoction. However, further rigorously designed, large-scale RCTs are needed to confirm these findings.
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http://dx.doi.org/10.1136/acupmed-2016-011332DOI Listing
April 2018

Comparison Between Oblique Pulling Spinal Manipulation and Other Treatments for Lumbar Disc Herniation: A Systematic Review and Meta-Analysis.

J Manipulative Physiol Ther 2018 Nov - Dec;41(9):771-779

College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong Province, China. Electronic address:

Objective: The purpose of this review was to compare oblique pulling spinal manipulation with other treatments for lumbar disc herniation.

Methods: Randomized controlled trials of oblique pulling manipulation versus other treatment for lumbar disc herniation were identified using the following databases: China National Knowledge Infrastructure, Wanfang Data, Chinese Science and Technology Periodical Database, PubMed, the Cochrane Library, Embase, Chinese Biological Medicine, and Web of Science. Data extraction was carried out based on inclusion and exclusion criteria, and meta-analysis were performed using RevMan 5.3 software.

Results: Nine relevant randomized controlled trials with a total of 887 patients were included. Meta-analysis revealed that oblique pulling manipulation was superior in effective rate to lumbar traction (risk ratio = 1.12; 95% confidence interval [CI]: 1.06-1.19; P < .01) and acupuncture (risk ratio = 1.22; 95% CI: 1.06-1.39; P < .01) and more effective in Visual Analog Scale score (mean difference = - 1.03, 95% CI: -1.32 to -0.74; P < .01) when compared to lumbar traction. It also demonstrated a favorable effect of modified oblique pulling manipulation in Japanese Orthopedic Association scores when compared with lumbar traction (mean difference = 1.66, 95% CI: 0.89 to 2.43; P < .01).

Conclusion: In the treatment of lumbar disc herniation, oblique pulling spinal manipulation presented with a higher effective rate than acupuncture and lumbar traction. Manipulation had a favorable effect in alleviating pain, and modified oblique pulling manipulation had significant superiority in improving lumbar function when compared with lumbar traction. However, considering the low methodological quality of included studies, more rigorously designed trials should be performed in the future.
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http://dx.doi.org/10.1016/j.jmpt.2018.04.005DOI Listing
November 2019

MicroRNA-27a contributes to the malignant behavior of gastric cancer cells by directly targeting PH domain and leucine-rich repeat protein phosphatase 2.

J Exp Clin Cancer Res 2017 03 21;36(1):45. Epub 2017 Mar 21.

Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin Province, China.

Background: Accumulating evidence indicates that microRNA-27a (miR-27a) is involved in carcinogenesis and tumor progression. However, the exact function and molecular mechanism of miR-27a in gastric cancer remain unclear.

Methods: Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of miR-27a and its target gene. The function of miR-27a in gastric cancer was investigated through in vitro and in vivo assays (MTT assay, colony formation assay, flow cytometry assay, wound healing assay, migration and invasion assay, immunohistochemistry (IHC), immunofluorescence (IF) and Western blot). A luciferase reporter assay was conducted to confirm the target gene of miR-27a.

Results: We found that miR-27a was commonly overexpressed in gastric cancer and high expression of miR-27a was associated with distant metastasis, lymph node metastasis, advanced T stage and advanced clinical stage. Functional assays demonstrated that overexpression of miR-27a in AGS cells accelerated cell proliferation, migration and invasion and suppressed apoptosis. Meanwhile, opposite results were observed in SGC-7901 cells when miR-27a was suppressed. Consistently, down-regulation of miR-27a inhibited the growth and metastasis of engrafted tumors in vivo. Furthermore, we found PH domain and leucine-rich repeat protein phosphatase 2 (PHLPP2) to be a new target of miR-27a, and downregulation of PHLPP2 could rescue the effect of anti-miR-27a in gastric cancer cells. In addition, miR-27a-mediated suppression of PHLPP2 led to stimulation of the AKT/GSK3β pathway.

Conclusions: Our data suggest that miR-27a functions as a crucial oncogenic miRNA in gastric cancer. It can promote proliferation and metastasis of tumor cells by suppressing PHLPP2 and activating the AKT/GSK3β pathway. Therefore, miR-27a is a potential novel therapeutic target in gastric cancer treatment.
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http://dx.doi.org/10.1186/s13046-017-0516-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361803PMC
March 2017

Upregulation of microRNA-574-3p in a human gastric cancer cell line AGS by TGF-β1.

Gene 2017 Mar 29;605:63-69. Epub 2016 Dec 29.

Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, Jilin Province, China. Electronic address:

The mechanisms that regulate miR-574-3p expression in cells remain elusive. In the present study, we used real-time PCR assay to demonstrate TGF-β1-induced miR-574-3p upregulation in AGS cells, which was inhibited by TGF-β receptor I inhibitor SB431542. We used a computer search to identify Smad binding sites upstream of the miR-574-3p precursor sequence. We demonstrated that silencing Smad4, but not Smad2 or Smad3, significantly inhibited the TGF-β1-induced miR-574-3p upregulation in AGS cells. Furthermore, TGF-β1 significantly increased the activity of a dual-luciferase reporter that contains the Smad binding sites upstream of the miR-574 precursor sequence. Silencing Smad4 significantly inhibited the TGF-β1-induced increase in the activity of the reporter in AGS cells. ChIP assay showed that Smad4 directly bound to the promoter of miR-574-3p. MiR-574-3p inhibition was effective in eliminating the inhibition of AGS cell proliferation induced by TGF-β1, suggesting that TGF-β1 inducing upregulation of miR-574-3p is functionally significant.
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http://dx.doi.org/10.1016/j.gene.2016.12.032DOI Listing
March 2017

Pre-Existing HCV Variants Resistant to DAAs and Their Sensitivity to PegIFN/RBV in Chinese HCV Genotype 1b Patients.

PLoS One 2016 3;11(11):e0165658. Epub 2016 Nov 3.

Department of Infectious Diseases, Peking University First Hospital, Beijing, China.

Background: The efficacy of direct-acting antiviral agents (DAAs) could be attenuated by the presence of resistance-associated variants (RAVs). The aim of this study was to investigate the natural prevalence of RAVs among Chinese HCV genotype 1b patients and analyze the efficacy of pegylated interferon (PegIFN)/ribavirin (RBV) therapy in patients with and without RAVs at baseline.

Methods: Direct sequencing of the HCV NS3, NS5A and NS5B regions was performed in baseline serum samples of 117 DAAs-naïve subjects infected with HCV genotype 1b. The efficacy of PegIFN/RBV therapy in patients with and without RAVs at baseline was analyzed by comparing the response rates between patients with RAVs and patients with wild type virus.

Results: The incidence of RAVs was 8.00% (8/100) in the NS3 region (T54S, n = 1, 1.00%; R117H, n = 5, 5.00%; S122T, n = 1, 1.00%; S174F, n = 1, 1.00%), 29.91% (32/107) in the NS5A region (L28M, n = 12, 11.21%; R30Q, n = 10, 9.35%; L31M, n = 1, 0.93%; P58S, n = 4, 3.74%; Y93H, n = 8, 7.48%) and 98.15% (106/108) in the NS5B region (L159F, n = 1, 0.93%; C316N, n = 103, 95.37%; A421V, n = 6, 5.56%). The response rates to PegIFN/RBV treatment did not differ between patients with or without RAVs in the NS5A region.

Conclusions: Pre-existing RAVs, including key RAVs, were detected in Chinese DAAs-naïve patients infected with HCV genotype 1b. IFN-based therapy could be a good option for patients with RAVs, especially key RAVs, at baseline.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165658PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094756PMC
July 2017

Resistance-associated mutations to HCV protease inhibitors naturally pre-existed in HIV/HCV coinfected, treatment-naïve patients.

Clin Res Hepatol Gastroenterol 2016 Nov 23;40(5):597-604. Epub 2016 Mar 23.

Department of Infectious Diseases, Peking University First Hospital, Peking University Health Science Center, No. 8 Xishiku Street, Xicheng District, Beijing, China. Electronic address:

Background And Objective: Presently, it has been approved to treat hepatitis C virus (HCV) infection with protease inhibitors (PIs). In the present study, we aimed to illustrate the natural prevalence of HCV NS3/4A PI resistance mutations in HIV/HCV coinfected, treatment-naïve patients.

Methods: Population sequence analysis of the NS3/4A protease was conducted in 96 HIV/HCV coinfected, treatment-naïve patients.

Results: Complete HCV NS3/4A sequence information was obtained from 70 (72.92%) samples, including 68 patients (97.14%) with genotype 1b and 2 patients (2.86%) with genotype 2a. A total of 21 patients (30.88%) of the 68 patients with HCV genotype 1b showed amino acid substitutions associated with HCV PI resistance. Mutation F43S was observed in 1.47% of patients with genotype 1b. The mutations of T54S, Q80K/R, R155K, A156G and D168A/E/G were found in 4.41%, 1.47%/1.47%, 2.94%, 23.53% and 1.47%/1.47%/1.47% of patients with genotype 1b, respectively. In addition, 4.41% of patients with genotype 1b showed double mutations in the NS3 region. The multiple mutations of Q80R+R155K+D168G and Q80K+R155K+A156G+D168A were detected in 1.47% and 1.47% of patients with HCV genotype 1b, respectively.

Conclusions: The most predominant HCV genotype was 1b in patients with HIV/HCV coinfection. Naturally occurring mutations resistant to HCV PIs (simeprevir, vaniprevir, boceprevir, telaprevir, asunaprevir and paritaprevir) pre-existed in patients with HIV/HCV genotype 1b coinfection. The effects of baseline PI resistance on treatment outcome should be further analyzed.
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http://dx.doi.org/10.1016/j.clinre.2016.02.004DOI Listing
November 2016

Streptomyces luozhongensis sp. nov., a novel actinomycete with antifungal activity and antibacterial activity.

Antonie Van Leeuwenhoek 2017 Feb 17;110(2):195-203. Epub 2016 Oct 17.

College of Life Science, Tarim University/Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin of Xinjiang Production & Construction Corps, 843300, Alar, People's Republic of China.

A novel actinomycete strain, designated TRM 49605, was isolated from a desert soil sample from Lop Nur, Xinjiang, north-west China, and characterised using a polyphasic taxonomic approach. The strain exhibited antifungal activity against the following strains: Saccharomyces cerevisiae, Curvularia lunata, Aspergillus flavus, Aspergillus niger, Fusarium oxysporum, Penicillium citrinum, Candida albicans and Candida tropicalis; Antibacterial activity against Bacillus subtilis, Staphylococcus epidermidis and Micrococcus luteus; and no antibacterial activity against Escherichia coli. Phylogenetic analysis based on 16S rRNA gene sequences affiliated strain TRM 49605 to the genus Streptomyces. Strain TRM 49605 shows high sequence similarities to Streptomyces roseolilacinus NBRC 12815 (98.62 %), Streptomyces flavovariabilis NRRL B-16367 (98.45 %) and Streptomyces variegatus NRRL B-16380 (98.45 %). Whole cell hydrolysates of strain TRM 49605 were found to contain LL-diaminopimelic acid as the diagnostic diamino acid and galactose, glucose, xylose and mannose as the major whole cell sugars. The major fatty acids in strain TRM 49605 were identified as iso C, anteiso C, C and Summed Feature 5 as defined by MIDI. The main menaquinones were identified as MK-9(H), MK-9(H), MK-9(H) and MK-10(H). The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol and phosphatidylinositol mannoside. The G+C content of the genomic DNA was determined to be 71.2 %. The DNA-DNA relatedness between strain TRM 49605 and the phylogenetically related strain S. roseolilacinus NBRC 12815 was 60.12 ± 0.06 %, which is lower than the 70 % threshold value for delineation of genomic prokaryotic species. Based on the phenotypic, chemotaxonomic and phylogenetic data, strain TRM 49605 (=CCTCC AA2015026 = KCTC 39666) should be designated as the type strain of a novel species of the genus Streptomyces, for which the name Streptomyces luozhongensis sp. nov. is proposed.
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http://dx.doi.org/10.1007/s10482-016-0790-6DOI Listing
February 2017

Pre-existing mutations related to tenofovir in chronic hepatitis B patients with long-term nucleos(t)ide analogue drugs treatment by ultra-deep pyrosequencing.

Oncotarget 2016 Oct;7(43):70264-70275

Department of Infectious Disease, Peking University First Hospital, Xicheng District, Beijing 100034, China.

Aims: The dynamics of resistance-associated mutations under combination therapy were explored.

Methods: A total of 46 patients were classified into adefovir (n=14) and entecavir (n=32) groups. In the adefovir (ADV) group, six patients receiving combined therapy were DNA-positive after more than 3 years of therapy. Ultra-deep pyrosequencing was used to analyze the dynamics of multi-drugs resistance mutations.

Results: At baseline, all 46 treatment-naïve patients harbored rtA181V/T substitutions (1.2%-4.6%) and rtN236T substitutions (1.6%-6.1%). In the ADV group, eight patients with long-term treatment were consecutively HBV DNA-positive for more than 3 years. During treatment, the rtA181T resistance-associated site appeared with increasing frequency in six of eight patients (NOs. 1-6), and two patients (NOs.4 and 8) carrying the rtA181T resistance mutations increasingly showed high levels of rtN236T. One patient (NO. 8) experienced virological breakthrough. Other known pre-existing mutations showed no dynamic fluctuations, including in rtA194T, rtP177G, rtF249A, and rtD263E. In addition to the common substitutions, some previously unknown amino acid substitutions, such as rtD134N, rtL145M/S, rtF151Y/L, rtR153Q, and rtS223A, should be further studied.

Conclusions: HBV-resistance substitutions conferring to nucleoside analogs are present at baseline. The dynamics of the HBV RT-region quasispecies variation are heterogeneous and complex.
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http://dx.doi.org/10.18632/oncotarget.11840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342551PMC
October 2016

Association of IL28B Genotypes and Baseline Serum Interferon-γ-Inducible- Protein-10 Levels with Treatment Response in Hepatitis C Virus Patients in China.

Gut Liver 2016 May;10(3):446-55

Department of Infectious Diseases, Peking University First Hospital, Beijing, China.

Background/aims: Several studies have demonstrated that serum interferon-γ-inducible-protein-10 (IP-10) levels at baseline and single nucleotide polymorphisms (SNPs) near the IL28B gene were associated with viral response and treatment outcomes. Our purpose was to assess the combination of pretreatment IP-10 levels with IL28B SNPs as predictors of treatment response to pegylated interferon α-2a plus ribavirin in patients infected with genotype 1 hepatitis C virus in China.

Methods: Seventy-two patients with chronic hepatitis C without fibrosis/cirrhosis were enrolled in the study. The virologic parameters and baseline serum IP-10 levels were determined. IL-28B genotypes were determined by sequencing.

Results: In this cohort, serum baseline IP-10 levels lower than 426.7 pg/mL could predict rapid virological response/ sustained virological response (SVR). Patients carrying favorable IL28B SNP genotypes had higher SVRs than did those carrying unfavorable variants (IL28B rs12979860, p=0.002; IL28B rs8099917, p=0.020). Combining both baseline IP- 10 and IL28B SNPs could improve the prediction of SVR in favorable allele carriers of IL28B, rs12979860 CC and rs8099917 TT. Serum baseline IP-10 levels and IL28B genotypes were independent predictors of SVR.

Conclusions: Our study shows that the combination of baseline serum IP-10 levels and the determination of IL28B SNPs increase the predictability of SVR rates in this cohort. (Gut Liver 2016;10446-455).
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http://dx.doi.org/10.5009/gnl15162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849699PMC
May 2016

Naturally occurring hepatitis C virus protease inhibitors resistance-associated mutations among chronic hepatitis C genotype 1b patients with or without HIV co-infection.

Hepatol Res 2016 May 5;46(6):552-8. Epub 2015 Nov 5.

Department of Infectious Diseases, Peking University First Hospital, Peking University Health Science Center, Beijing, China.

Unlabelled: The aim of this study was to measure the frequency of natural mutations in hepatitis C virus (HCV) mono-infected and HIV/HCV co-infected protease inhibitor (PI)-naive patients.

Methods: Population sequence of the non-structural (NS)3 protease gene was evaluated in 90 HCV mono-infected and 96 HIV/HCV co-infected PI treatment-naive patients. The natural prevalence of PI resistance mutations in both groups was compared.

Results: Complete HCV genotype 1b NS3 sequence information was obtained for 152 (81.72%) samples. Seven sequences (8.33%) of the 84 HCV mono-infected patients and 21 sequences (30.88%) of the 68 HIV/HCV co-infected patients showed amino acid substitutions associated with HCV PI resistance. There was a significant difference in the natural prevalence of PI resistance mutations between these two groups (P = 0.000). The mutations T54S, R117H and N174F were observed in 1.19%, 5.95% and 1.19% of HCV mono-infected patients. The mutations F43S, T54S, Q80K/R, R155K, A156G/V, D168A/E/G and V170A were found in 1.47%, 4.41%, 1.47%/1.47%, 2.94%, 23.53%/1.47%, 1.47%/1.47%/1.47% and 1.47% of HIV/HCV co-infected patients, respectively. In addition, the combination mutations in the NS3 region were detected only in HIV/HCV genotype 1b co-infected patients.

Conclusion: Naturally occurring HCV PI resistance mutations existed in HCV mono-infected and HIV/HCV co-infected genotype 1b PI-naive patients. HIV co-infection was associated with a greater frequency of PI resistance mutations. The impact of HIV infection on baseline HCV PI resistance mutations and treatment outcome in chronic hepatitis C (CHC) patients should be further analyzed.
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http://dx.doi.org/10.1111/hepr.12590DOI Listing
May 2016
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