Publications by authors named "Tang Hong"

835 Publications

Clinical Inertia and 2-Year Glycaemic Trajectories in Patients with Non-Newly Diagnosed Type 2 Diabetes Mellitus in Primary Care: A Retrospective Cohort Study.

Patient Prefer Adherence 2021 11;15:2497-2508. Epub 2021 Nov 11.

Department of Endocrinology, Beijing Ruijing Diabetes Hospital, Beijing, 100079, People's Republic of China.

Objective: To analyse diabetes treatment, treatment change and self-management behaviours in association with 2-year glycaemic trajectories in patients with non-newly diagnosed type 2 diabetes mellitus in Chinese primary care.

Methods: This was an observational, multi-centre, longitudinal, retrospective cohort study. Clinical data of 4690 subjects were extracted from electronic medical records, including serial glycated haemoglobin A (HbA) measurements, antidiabetic medication records and compliance to exercise, diet, medications and self-monitoring of blood glucose (SMBG). Patterns of longitudinal HbA1c trajectories were identified using the percentage of HbA measurements <7.5% from the second available HbA measurement. Clinical relevance of the clusters was assessed through multivariable analysis.

Results: Approximately half of the participants demonstrated good glycaemic control; of these, 34.5% demonstrated stable, good control, and 13.7% demonstrated relatively good control. About 16.2% demonstrated moderate control, and 35.6% demonstrated poor control. From the good to poor control groups, the percentage of subjects treated with insulin at baseline and during the follow-up period increased gradually, while the percentage of subjects adhering to exercise, diet, medications and SMBG decreased gradually. Compared with baseline, the adherence to exercise, diet, medications and SMBG improved significantly. Approximately 50% and 26% of subjects in the two poorest control groups, respectively, experienced treatment changes. After multivariable adjustments, baseline HbA ≥7.5%, HbA change ≥-0.5% from baseline to visit 1, insulin treatment, treatment change, poor adherence to diet, exercise, SMBG during the follow-up period and HbA measurements <3 per year were significantly associated with poorer glycaemic control.

Conclusion: We identified four longitudinal HbA trajectories in patients with non-newly diagnosed type 2 diabetes. Even if baseline HbA is suboptimal, aggressive treatment changes, good adherence during the follow-up period, ≥3 HbA measurements per year and reducing HbA levels to a certain extent by the first follow-up visit were important for good, stable, long-term glycaemic control.
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http://dx.doi.org/10.2147/PPA.S328165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593594PMC
November 2021

Effects of aging on the histology and biochemistry of rat tendon healing.

BMC Musculoskelet Disord 2021 Nov 15;22(1):949. Epub 2021 Nov 15.

Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing, 400038, China.

Introduction: Tendon diseases and injuries are a serious problem for the aged population, often leading to pain, disability and a significant decline in quality of life. The purpose of this study was to determine the influence of aging on biochemistry and histology during tendon healing and to provide a new strategy for improving tendon healing.

Method: A total of 24 Sprague-Dawley rats were equally divided into a young and an aged group. A rat patellar tendon defect model was used in this study. Tendon samples were collected at weeks 2 and 4, and hematoxylin-eosin, alcian blue and immunofluorescence staining were performed for histological analysis. Meanwhile, reverse transcription-polymerase chain reaction (RT-PCR) and western blot were performed to evaluate the biochemical changes.

Results: The histological scores in aged rats were significantly lower than those in young rats. At the protein level, collagen synthesis-related markers Col-3, Matrix metalloproteinase-1 and Metallopeptidase Inhibitor 1(TIMP-1) were decreased at week 4 in aged rats compared with those of young rats. Though there was a decrease in the expression of the chondrogenic marker aggrecan at the protein level in aged tendon, the Micro-CT results from weeks 4 samples showed no significant difference(p>0.05) on the ectopic ossification between groups. Moreover, we found more adipocytes accumulated in the aged tendon defect with the Oil Red O staining and at the gene and protein levels the markers related to adipogenic differentiation.

Conclusions: Our findings indicate that tendon healing is impaired in aged rats and is characterized by a significantly lower histological score, decreased collagen synthesis and more adipocyte accumulation in patellar tendon after repair.
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http://dx.doi.org/10.1186/s12891-021-04838-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594129PMC
November 2021

Histologic and biomechanical evaluation of the thoracolumbar fascia graft for massive rotator cuff tears in a rat model.

J Shoulder Elbow Surg 2021 Nov 11. Epub 2021 Nov 11.

Department of Orthopedic Surgery, Southwest Hospital, Army Military Medical University, Chongqing, China. Electronic address:

Background: Fascial autografts, which are easily available grafts, have provided a promising option in patients with massive rotator cuff tears. However, no fascial autografts other than the fascia lata have been reported, and the exact healing process of the fascia-to-bone interface is not well understood. The objective of this study is to histologically and biomechanically evaluate the effect of the thoracolumbar fascia (TLF) on fascia-to-bone healing.

Methods: A total of 88 rats were used in this study. Eight rats were sacrificed at the beginning to form an intact control group, and the other rats were divided randomly into 2 groups (40 rats per group): the thoracolumbar fascia augmentation group (TLF group) and the repair group (R group). The right supraspinatus was detached, and a 3*5 mm defect of the supraspinatus was created. The thoracolumbar fascia was used to augment the torn supraspinatus in the TLF group, whereas in the R group, the torn supraspinatus was repaired in only a transosseous manner. Histology and biomechanics were assessed at 1, 2, 4, 8 and 16 weeks postoperatively.

Results: The modified tendon maturation score of the TLF group was higher than that of the R group at 8 weeks (23.00 ± 0.71 vs. 24.40 ± 0.89, P=.025) and 16 weeks (24.60 ± 0.55 vs. 26.40 ± 0.55, P≤.001). The TLF group showed a rapid vascular reaction, and the peak value appeared at 1 week. Later, the capillary density decreased, and almost no angiogenesis was observed at 8 weeks postoperatively. Immunohistochemistry results demonstrated a significantly higher percentage of collagen I in the TLF group at 4, 8 and 16 weeks (24.78% ± 2.76% vs. 20.67% ± 2.11% at 4 weeks, p=.046; 25.46% ± 1.77% vs. 21.49% ± 2.33% at 8 weeks, p=.026; 34.77% ± 2.25% vs. 30.01% ± 3.17% at 16 weeks, p=.040) postoperatively. Biomechanical tests revealed that the ultimate failure force in the TLF group was significantly higher than that in the R group at the final evaluation (29.13 ± 2.49 N vs. 23.10 ± 3.47 N, p=.022).

Conclusions: The TLF autograft can promote a faster biological healing process and a better fixation strength. It could be used as an alternative reinforcement or bridging patch when the fascia lata is not appropriate or available for SCR.

Level Of Evidence: Basic Science Study; Histology and Biomechanics.
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http://dx.doi.org/10.1016/j.jse.2021.10.019DOI Listing
November 2021

MiR-6924-5p-rich exosomes derived from genetically modified Scleraxis-overexpressing PDGFRα(+) BMMSCs as novel nanotherapeutics for treating osteolysis during tendon-bone healing and improving healing strength.

Biomaterials 2021 Nov 5;279:121242. Epub 2021 Nov 5.

Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, 400000, China. Electronic address:

Osteolysis at the tendon-bone interface can impair pullout strength during tendon-bone healing and lead to surgery failure, but the effects of clinical treatments are not satisfactory. Mesenchymal stem cell (MSC)-derived exosomes have been used as potent and feasible natural nanocarriers for drug delivery and have been proven to enhance tendon-bone healing strength, indicating that MSC-derived exosomes could be a promising therapeutic strategy. In this study, we explored Scleraxis (Scx) dynamically expressed in PDGFRα(+) bone marrow-derived mesenchymal stem cells (BMMSCs) during natural tendon-bone healing. Then, we investigated the role of PDGFRα(+) BMMSCs in tendon-bone healing after Scx overexpression as well as the underlying mechanisms. Our data demonstrated that Scx-overexpressing PDGFRα(+) BMMSCs (BMMSC) could efficiently inhibit peritunnel osteolysis and enhance tendon-bone healing strength by preventing osteoclastogenesis in an exosomes-dependent manner. Exosomal RNA-seq revealed that the abundance of a novel miRNA, miR-6924-5p, was highest among miRNAs. miR-6924-5p could directly inhibit osteoclast formation by binding to the 3'-untranslated regions (3'UTRs) of OCSTAMP and CXCL12. Inhibition of miR-6924-5p expression reversed the prevention of osteoclastogenic differentiation by BMMSC derived exosomes (BMMSC-exos). Local injection of BMMSC-exos or miR-6924-5p dramatically reduced osteoclast formation and improved tendon-bone healing strength. Furthermore, delivery of miR-6924-5p efficiently inhibited the osteoclastogenesis of human monocytes. In brief, our study demonstrates that BMMSC-exos or miR-6924-5p could serve as a potential therapy for the treatment of osteolysis during tendon-bone healing and improve the outcome.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121242DOI Listing
November 2021

Association between longer duration of citrate accumulation and 90-day mortality of acute-on-chronic liver failure.

Crit Care 2021 Nov 11;25(1):387. Epub 2021 Nov 11.

Center of Infectious Diseases, West China Hospital of Sichuan University, No. 37 GuoXue Xiang, Wuhou District, Chengdu, 610041, China.

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http://dx.doi.org/10.1186/s13054-021-03819-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588580PMC
November 2021

Cross-sectional examination of 24-hour movement behaviours among 3- and 4-year-old children in urban and rural settings in low-income, middle-income and high-income countries: the SUNRISE study protocol.

BMJ Open 2021 10 25;11(10):e049267. Epub 2021 Oct 25.

Department of Sports Science and Physical Education, The Chinese University of Hong Kong, Hong Kong, Hong Kong.

Introduction: 24-hour movement behaviours (physical activity, sedentary behaviour and sleep) during the early years are associated with health and developmental outcomes, prompting the WHO to develop Global guidelines for physical activity, sedentary behaviour and sleep for children under 5 years of age. Prevalence data on 24-hour movement behaviours is lacking, particularly in low-income and middle-income countries (LMICs). This paper describes the development of the protocol, designed to address this gap.

Methods And Analysis: SUNRISE is the first international cross-sectional study that aims to determine the proportion of 3- and 4-year-old children who meet the WHO Global guidelines. The study will assess if proportions differ by gender, urban/rural location and/or socioeconomic status. Executive function, motor skills and adiposity will be assessed and potential correlates of 24-hour movement behaviours examined. Pilot research from 24 countries (14 LMICs) informed the study design and protocol. Data are collected locally by research staff from partnering institutions who are trained throughout the research process. Piloting of all measures to determine protocol acceptability and feasibility was interrupted by COVID-19 but is nearing completion. At the time of publication 41 countries are participating in the SUNRISE study.

Ethics And Dissemination: The SUNRISE protocol has received ethics approved from the University of Wollongong, Australia, and in each country by the applicable ethics committees. Approval is also sought from any relevant government departments or organisations. The results will inform global efforts to prevent childhood obesity and ensure young children reach their health and developmental potential. Findings on the correlates of movement behaviours can guide future interventions to improve the movement behaviours in culturally specific ways. Study findings will be disseminated via publications, conference presentations and may contribute to the development of local guidelines and public health interventions.
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http://dx.doi.org/10.1136/bmjopen-2021-049267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547512PMC
October 2021

Adipogenic differentiation was inhibited by downregulation of PPARγ signaling pathway in aging tendon stem/progenitor cells.

J Orthop Surg Res 2021 Oct 18;16(1):614. Epub 2021 Oct 18.

Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing, 400038, China.

Background: Tendon stem/progenitor cells (TSPCs) play a vital role in tendon repair and regeneration. Previously we found more adipocytes accumulated in the patellar tendon injury sites in aging rats compared with the young ones, of which the mechanism is still unknown. Here, we want to identify whether erroneous differentiation of TSPCs by aging accounts for the adipocyte accumulation.

Methods: TSPCs from young and aging rats were isolated and propagated. Both young and aging TSPCs were induced to differentiate into adipocytes, and Oil red O staining, quantitative real-time polymerase chain reaction (qRT-PCR), western-blot and immunofluorescent staining were used to evaluate the capability of TSPCs. RNA sequencing was utilized to screen out different genes and signaling pathways related to adipogenesis between young and aging TSPCs.

Results: The Oil red O staining showed there were more adipocytes formed in young TSPCs. Besides, adipogenic markers perilipin, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding proteins alpha (C/EBPα) and Fatty acid-binding protein 4 (FABP4) were elevated both at gene and protein level. PPARγ signaling pathway was selected as our target via RNA sequencing. After adding the signaling activators, Rosiglitazone maleate (RM), inhibited adipogenesis of aging TSCs was reversed.

Conclusions: In conclusion, aging inhibited adipogenesis of TSPCs by down-regulating PPARγ signaling. It is not likely that the adipocyte accumulation in aging tendon during repair was due to the aging of TSPCs. This may provide new targets for curing aging tendon injuries or tendinopathies.
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http://dx.doi.org/10.1186/s13018-021-02720-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522149PMC
October 2021

Unmet needs in occupational health: prevention and management of viral hepatitis in healthcare workers in Ho Chi Minh City, Vietnam: a mixed-methods study.

BMJ Open 2021 10 12;11(10):e052668. Epub 2021 Oct 12.

Vietnam Viral Hepatitis Alliance, Reston, Virginia, USA

Objectives: Vietnam is an endemic area for hepatitis B virus and hepatitis C virus infection (HBV-HCV), yet its largest city, Ho Chi Minh City (HCMC), has no comprehensive policy to educate, screen, treat and protect healthcare workers (HCWs) from viral hepatitis. We conducted a mixed-methods study to document HBV-HCV infection rates, risk factors, local barriers and opportunities for providing education, screening and medical care for HCWs.

Design: This mixed-methods study involved an HBV and HCV serological evaluation, knowledge, attitude and practice survey about viral hepatitis and many in-depth interviews. Descriptive statistics and thematic content analysis using inductive and deductive approaches were used.

Setting: HCMC, Vietnam.

Participants: HCWs at risk of viral hepatitis exposure at three hospitals in HCMC.

Results: Of the 210 invited HCWs, 203 were enrolled. Of the 203 HCWs enrolled, 20 were hepatitis B surface antigen-positive, 1 was anti-hepatitis C antibody (anti-HCV Ab)-positive, 57 were anti-hepatitis B core Ab-positive and 152 had adequate anti-hepatitis B surface Ab (anti-HBs Ab) titre (≥10IU/mL). Only 50% of the infected HCWs reported always using gloves during a clinical activity involving handling of blood or bodily fluid. Approximately 50% of HCWs were still not vaccinated against HBV following 1 year of employment. In-depth interviews revealed two major concerns for most interviewees: the need for financial support for HBV-HCV screening and treatment in HCWs and the need for specific HBV-HCV guidelines to be independently developed.

Conclusions: The high HBV infection rate in HCWs coupled with inadequate preventive occupational practices among the population in HCMC highlight the urgent needs to establish formal policy and rigorous education, screening, vaccination and treatment programmes to protect HCWs from HBV acquisition or to manage those living with chronic HBV in Vietnam.
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http://dx.doi.org/10.1136/bmjopen-2021-052668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513255PMC
October 2021

Effect of baseline physical activity on the fat gain of adolescents in a 5-year cohort study in Ho Chi Minh City, Viet Nam.

Br J Nutr 2021 Oct 8:1-7. Epub 2021 Oct 8.

The Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, NSW2006Australia.

Differences in physical activity (PA) might lead to long-term weight control. Studies on inverse relations between PA and changes in fatness among adolescents are limited. This paper examined the effect of PA on adolescents' changing body fatness over 5 years in Ho Chi Minh City (HCMC). Two hundred thirty-five boys and 247 girls who have had skinfold thickness measurements in the baseline survey in 2004 were selected to follow yearly. We estimated PA as the average number of accelerometers' counts/h. Slopes of triceps, sub-scapular skinfolds and BMI were calculated and classified as increasing or stable/decreasing. To assess the effects of the low level of activity (i.e. below the median of the average number of counts) on the fat gain (i.e. increasing slopes), relative risk and 95 % CI were estimated using Poisson regression. The average number of counts/h in boys (7·8) was significantly higher than that in girls (5·0) (P < 0·001). On average, active girls still gained 0·51 mm in triceps skinfold (TSF) over 5 years, while active boys lost 0·12 mm. After controlling for baseline energy intake, baseline triceps and baseline age, inactive adolescents were 1·39 times higher than active ones to increase the slope of triceps (95 % CI 1·19, 1·63). The risk ratio was 1·62 for those with more body fat at baseline. In general, inactive students gained substantially more subcutaneous fat, especially in their TSF, than more active ones. Thus, strategies to prevent adolescent obesity in HCMC should consider the important role of PA to control this problem in adolescents effectively.
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http://dx.doi.org/10.1017/S0007114521004098DOI Listing
October 2021

Integrated Approaches for COVID-19 Case Finding and Their Impact on Timeliness for Disease Containment - Changning District, Shanghai Municipality, China, January-July, 2020.

China CDC Wkly 2021 Jul;3(27):576-580

Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.

The demand for containing the virus and protecting the economy is high on the agenda of policymakers during the coronavirus disease 2019 (COVID-19) pandemic. Modelling studies indicated that highly effective contact tracing and case isolation were enough to contain the spread of COVID-19 at the early stages, but this has not been validated in real world contexts.



Integrated case finding approaches, including outpatient monitoring, exposed people quarantining, and contact tracing, effectively contained the spread of COVID-19 in a densely populated district in Shanghai Municipality, China. Active case-finding involving quarantine of exposed persons and contact tracing could reduce the time from symptom onset to COVID-19 diagnosis, thus reducing the risk of local transmission.



Active case-finding should be prioritized as an effective approach to minimize the risk of local transmission in future pandemics. Integrated COVID-19 case finding approaches applied in Shanghai may inform public health policy in other regions where strict lockdown is not applicable.
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http://dx.doi.org/10.46234/ccdcw2021.149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392964PMC
July 2021

Downregulation of Perilipin1 by the Immune Deficiency Pathway Leads to Lipid Droplet Reconfiguration and Adaptation to Bacterial Infection in .

J Immunol 2021 11 29;207(9):2347-2358. Epub 2021 Sep 29.

The Center for Microbes, Development, and Health, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China;

Lipid droplets (LDs), the highly dynamic intracellular organelles, are critical for lipid metabolism. Dynamic alterations in the configurations and functions of LDs during innate immune responses to bacterial infections and the underlying mechanisms, however, remain largely unknown. In this study, we trace the time-course morphology of LDs in fat bodies of after transient bacterial infection. Detailed analysis shows that (), a core gene involved in the regulation of LDs, is suppressed by the immune deficiency signaling, one major innate immune pathway in During immune activation, downregulated promotes the enlargement of LDs, which in turn alleviates immune reaction-associated reactive oxygen species stress. Thus, the growth of LDs is likely an active adaptation to maintain redox homeostasis in response to immune deficiency activation. Therefore, our study provides evidence that serves as a modulator on LDs' reconfiguration in regulating infection-induced pathogenesis, and plin1 might be a potential therapeutic target for coordinating inflammation resolution and lipid metabolism.
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http://dx.doi.org/10.4049/jimmunol.2100343DOI Listing
November 2021

Identifying Prokineticin2 as a Novel Immunomodulatory Factor in Diagnosis and Treatment of Sepsis.

Crit Care Med 2021 Sep 27. Epub 2021 Sep 27.

Department of Clinical Laboratory, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, China. Department of Critical Care Medicine, Department of Surgical Intensive Care Unit, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China. Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine, Chongqing Medical University, Chongqing, China. Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, ChongQing Medical University, Chongqing, China. Key Laboratory of RNA Biology, National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.

Objectives: Sepsis remains a highly lethal disease, whereas the precise reasons for death remain poorly understood. Prokineticin2 is a secreted protein that regulates diverse biological processes. Whether prokineticin2 is beneficial or deleterious to sepsis and the underlying mechanisms remain unknown.

Design: Prospective randomized animal investigation and in vitro studies.

Setting: Research laboratory at a medical university hospital.

Subjects: Prokineticin2 deficiency and wild-type C57BL/6 mice were used for in vivo studies; sepsis patients by Sepsis-3 definitions, patient controls, and healthy controls were used to obtain blood for in vitro studies.

Interventions: Prokineticin2 concentrations were measured and analyzed in human septic patients, patient controls, and healthy individuals. The effects of prokineticin2 on sepsis-related survival, bacterial burden, organ injury, and inflammation were assessed in an animal model of cecal ligation and puncture-induced polymicrobial sepsis. In vitro cell models were also used to study the role of prokineticin2 on antibacterial response of macrophages.

Measurements And Main Results: Prokineticin2 concentration is dramatically decreased in the patients with sepsis and septic shock compared with those of patient controls and healthy controls. Furthermore, the prokineticin2 concentration in these patients died of sepsis or septic shock is significantly lower than those survival patients with sepsis or septic shock, indicating the potential value of prokineticin2 in the diagnosis of sepsis and septic shock, as well as the potential value in predicting mortality in adult patients with sepsis and septic shock. In animal model, recombinant prokineticin2 administration protected against sepsis-related deaths in both heterozygous prokineticin2 deficient mice and wild-type mice and alleviated sepsis-induced multiple organ damage. In in vitro cell models, prokineticin2 enhanced the phagocytic and bactericidal functions of macrophage through signal transducers and activators of transcription 3 pathway which could be abolished by signal transducers and activators of transcription 3 inhibitors S3I-201. Depletion of macrophages reversed prokineticin2-mediated protection against polymicrobial sepsis.

Conclusions: This study elucidated a previously unrecognized role of prokineticin2 in clinical diagnosis and treatment of sepsis. The proof-of-concept study determined a central role of prokineticin2 in alleviating sepsis-induced death by regulation of macrophage function, which presents a new strategy for sepsis immunotherapy.
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http://dx.doi.org/10.1097/CCM.0000000000005335DOI Listing
September 2021

Aluminum nitride nanophotonics for beyond-octave soliton microcomb generation and self-referencing.

Nat Commun 2021 Sep 14;12(1):5428. Epub 2021 Sep 14.

Department of Electrical Engineering, Yale University, New Haven, CT, 06511, USA.

Frequency microcombs, alternative to mode-locked laser and fiber combs, enable miniature rulers of light for applications including precision metrology, molecular fingerprinting and exoplanet discoveries. To enable frequency ruling functions, microcombs must be stabilized by locking their carrier-envelope offset frequency. So far, the microcomb stabilization remains compounded by the elaborate optics external to the chip, thus evading its scaling benefit. To address this challenge, here we demonstrate a nanophotonic chip solution based on aluminum nitride thin films, which simultaneously offer optical Kerr nonlinearity for generating octave soliton combs and quadratic nonlinearity for enabling heterodyne detection of the offset frequency. The agile dispersion control of crystalline aluminum nitride photonics permits high-fidelity generation of solitons with features including 1.5-octave spectral span, dual dispersive waves, and sub-terahertz repetition rates down to 220 gigahertz. These attractive characteristics, aided by on-chip phase-matched aluminum nitride waveguides, allow the full determination of the offset frequency. Our proof-of-principle demonstration represents an important milestone towards fully integrated self-locked microcombs for portable optical atomic clocks and frequency synthesizers.
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http://dx.doi.org/10.1038/s41467-021-25751-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440561PMC
September 2021

Anthropometric Indicators to Estimate Percentage of Body Fat: A Comparison Using Cross-Sectional Data of Children and Adolescents in Ho Chi Minh City, Vietnam.

Indian J Pediatr 2021 Sep 13. Epub 2021 Sep 13.

Department of Outreach and International, Childrens Hospital 1, Ho Chi Minh City, Vietnam.

Objectives: To compare the association between waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body mass index (BMI), and percentage of body fat (PBF) measured by dual energy X-ray absorptiometry (DXA) method in children and adolescents of Vietnam.

Methods: This cross-sectional study included 153 children and adolescents aged 6-18 y old in Ho Chi Minh City, Vietnam. Correlations between indicators were determined using Pearson correlation coefficient (r). Linear regression was carried out with PBF as dependent variable to test the further association of potential indicators.

Results: The strongest correlation was found between PBF and WHtR in all pubertal stages (0.712; 0.556; 0.638 in male; 0.635; 0.799; 0.611 in female, respectively). The regression analysis indicated that WHtR was the most effective estimator of PBF ([Formula: see text] = 0.69, RMSE = 4.54 for male; [Formula: see text] = 0.50, RMSE = 4.34 for female) in the model including pubertal stage variable for each gender.

Conclusions: The results support the use of WHtR as an effective indicator for detecting adiposity in Vietnamese children and adolescents.
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http://dx.doi.org/10.1007/s12098-021-03882-7DOI Listing
September 2021

Significantly Decreased Islet Cell Function is Closely Associated with Hyperglycemia in Chronic Hepatitis B Patients.

Int J Endocrinol 2021 24;2021:1264707. Epub 2021 Aug 24.

Center of Infectious Diseases, Sichuan University West China Hospital, Chengdu, China.

Aim: This study is aimed at the characteristics of glucose metabolism and islet cell function evaluated by the homeostasis model assessment of cell function (HOMA-) value and its risk factors in chronic hepatitis B (CHB) patients.

Method: This cross-sectional study recruited 110 CHB patients (CHB group) and 110 patients without hepatitis B virus (non-HBV group); the groups were matched according to sex, age, and body mass index under the same glucose metabolism status. The risk factors, characteristics, and differences in glucose metabolism and HOMA- values between the two groups were analyzed.

Results: The abnormal glucose metabolism rate was higher in CHB patients with liver cirrhosis (LC) or hepatitis B envelope antigen (HBeAg) (-) status. In addition, under the same glucose metabolism status, the fasting plasma glucose (FPG) levels and 2-hour postprandial plasma glucose (2h-PG) levels in the CHB group were higher, while the HOMA- values were significantly lower and the homeostasis model assessment of insulin resistance (HOMA-IR) value was not higher than that in the non-HBV group (all < 0.0001). Further analyses revealed that the main risk factors for abnormal glucose metabolism were HBeAg (-) status and hepatitis B envelope antibody levels. But HBV serological and virological indicators had no effects on the HOMA- values.

Conclusion: Islet cell function in patients with CHB was compromised, which is closely associated with fasting and postprandial hyperglycemia in chronic hepatitis B patients. Further research should be done to verify the compromised islet cell function and then to investigate the mechanisms behind the effect of hepatitis B virus infection on islet cell function in CHB patients.
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http://dx.doi.org/10.1155/2021/1264707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421157PMC
August 2021

Efficacy of different nucleoside analog rescue therapies for entecavir-resistant chronic hepatitis B patients.

BMC Infect Dis 2021 Sep 6;21(1):912. Epub 2021 Sep 6.

Center of Infectious Diseases, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.

Background: Entecavir (ETV) is recommended as a first-line anti-HBV treatment. However, many chronic hepatitis B patients initiate anti-HBV treatment such as lamivudine and telbivudine with low genetic barriers in China, which leads to compensatory mutations and increases the rate of ETV resistance. The management of ETV resistance in China is an essential clinical issue.

Methods: Patients from 2011 to 2017 with nucleos(t)ide analog resistance were screened and 72 patients with ETV resistance were included. These patients received different rescue therapies including an ETV and adefovir (ADV) combination therapy group (n = 25), a tenofovir (TDF) monotherapy group (n = 27), and an ETV and TDF combination therapy group (n = 20). Virologic, biochemical, and serologic responses were compared among the three groups.

Results: The rate of ETV resistance among all HBV-resistant variants increased from 6.04% in 2011 to 15.02% in 2017. TDF monotherapy and TDF combination groups showed similar rates of negative HBV DNA at 48 weeks (74.07% vs 70.00%, P > 0.05), while the ETV and ADV group showed the worst virologic response (28.00%). Also, TDF monotherapy and TDF combination therapy showed similar decline of HBV DNA at weeks 12, 24, and 48. There was no significant difference in the rates of HBeAg clearance, ALT normalization, and abnormal renal function among the three groups.

Conclusions: TDF monotherapy showed a comparable virologic response to TDF and ETV combination therapy and a better virologic response than ETV and ADV combination therapy. Thus, TDF monotherapy is the preferred rescue therapy for ETV resistance.
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http://dx.doi.org/10.1186/s12879-021-06554-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420064PMC
September 2021

Immunization with the receptor-binding domain of SARS-CoV-2 elicits antibodies cross-neutralizing SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement.

Cell Discov 2020 Sep 3;6(1):61. Epub 2020 Sep 3.

CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Center for Biosafety Mega-Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.

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http://dx.doi.org/10.1038/s41421-020-00199-1DOI Listing
September 2020

Femtosecond laser-induced periodic grooves and nanopore clusters make a synergistic effect on osteogenic differentiation.

Colloids Surf B Biointerfaces 2021 Dec 4;208:112021. Epub 2021 Aug 4.

Department of Orthopedics/Sports Medicine Center, The First Affiliated Hospital of Army Medical University of Chinese PLA, Chongqing, 400038, PR China. Electronic address:

Polyether-ether-ketone (PEEK) materials have good biocompatibility, excellent corrosion resistance, chemical stability and an elastic modulus close to that of natural bone. However, due to its biological inertness, PEEK may affect osteogenic differentiation and leads to osseointegration failure, though PEEK is expected to improve osseointegration. In this work, by changing the power of femtosecond laser, micro-grooves are made on the PEEK surface. As observed by scanning electron microscopy, the trench has a periodic structure, the micro shape is neat, and the trench is also covered with nanometer-level pore clusters. In the in vitro culture experiments, through the proliferation experiment of mouse bone marrow mesenchymalstem cells (mBMSCs), cell viability analysis and alkaline phosphatase activity analysis, it is proven that after femtosecond laser treatment of the PEEK surface, the micro-grooves on the surface and the nanopore clusters due to laser energy ablation can produce a synergistic effect, enhancing the osteogenic differentiation ability of cells, and improving the bone integration ability of PEEK materials.
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http://dx.doi.org/10.1016/j.colsurfb.2021.112021DOI Listing
December 2021

Prevalence of Physical Activity, Screen Time, and Sleep, and Associations with Adiposity and Motor Development among Preschool-Age Children in Vietnam: The SUNRISE Vietnam Pilot Study.

Indian J Pediatr 2021 Aug 18. Epub 2021 Aug 18.

Department of Epidemiology, Faculty of Public Health, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, 70000, Vietnam.

Objectives: Global childhood obesity is of great concern. In 2019, the World Health Organization released global guidelines on movement behaviors for the children under 5 y of age to combat this epidemic. This study aimed to estimate the prevalence of Vietnamese preschoolers meeting the guidelines, and examined whether guideline compliance is associated with adiposity and motor development.

Methods: A cross-sectional study was conducted on 103 healthy preschoolers who were conveniently sampled from preschools in urban and rural areas around Ho Chi Minh city. Time spent in different intensities of physical activity and sedentary behavior was measured using Actigraph GT3X + accelerometers over three consecutive days. Sleep and screen time were obtained via parent questionnaires. Children were classified as meeting or not meeting the global guidelines. Height, weight, and motor skills were measured by the research staff. Regression models were applied to quantify the association between guideline compliance and adiposity and motor development, adjusting for age and sex.

Results: While 17.5% of children met all three guidelines, 5.8% met no guidelines. The prevalences of children who met guidelines for physical activity time, sleep duration, and screen time were 50.4%, 81.4%, and 44.7%, respectively. There was no association between guideline compliance and adiposity and motor development.

Conclusion: This study found a low proportion of children who met the global guidelines, whereas a high proportion of those with overweight and obesity was reported. Health programs should promote more physical activities of various intensities in young children.
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http://dx.doi.org/10.1007/s12098-021-03895-2DOI Listing
August 2021

Emerging Regulatory Mechanisms Involved in Liver Cancer Stem Cell Properties in Hepatocellular Carcinoma.

Front Cell Dev Biol 2021 22;9:691410. Epub 2021 Jul 22.

Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China.

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and one of the leading causes of cancer-related deaths worldwide. A growing body of evidence supports the hypothesis that HCC is driven by a population of cells called liver cancer stem cells (LCSCs). LCSCs have been proposed to contribute to malignant HCC progression, including promoting tumor occurrence and growth, mediating tumor metastasis, and treatment resistance, but the regulatory mechanism of LCSCs in HCC remains unclear. Understanding the signaling pathways responsible for LCSC maintenance and survival may provide opportunities to improve patient outcomes. Here, we review the current literature about the origin of LCSCs and the niche composition, describe the current evidence of signaling pathways that mediate LCSC stemness, then highlight several mechanisms that modulate LCSC properties in HCC progression, and finally, summarize the new developments in therapeutic strategies targeting LCSCs markers and regulatory pathways.
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http://dx.doi.org/10.3389/fcell.2021.691410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339910PMC
July 2021

Prediction of Rivaroxaban-Rifampin Interaction After Major Orthopedic Surgery: Physiologically Based Pharmacokinetic Modeling and Simulation.

Front Pharmacol 2021 23;12:706781. Epub 2021 Jul 23.

Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.

Rivaroxaban is commonly used for the prophylaxis of venous thromboembolism (VTE) for patients undergoing major orthopedic surgery. Rivaroxaban is primarily eliminated by hepatic CYP450 metabolism and renal excretion. Rifampin is a commonly used antibiotic for prosthetic joint infections (PJI) and a potent inducer of CYP450 enzymes. Clinical data about drug-drug interactions of rivaroxaban and rifampin are limited. The present study is to describe DDI of rivaroxaban and rifampin in several prosthetic joint infections patients undergoing major orthopedic surgery. We retrospectively identified six patients concomitantly administered with rivaroxaban and rifampin between 2019 and 2020. Plasma samples of these patients with accurate sampling time were chosen from the biobank and plasma levels of rivaroxaban were measured at each time point. A physiologically based pharmacokinetic model for the rivaroxaban-rifampin interaction was developed to predict the optimal dosing regimen of rivaroxaban in the case of co-medication with rifampin. The model was validated by the observed plasma concentration of rivaroxaban from the above patients. From this model, it could be simulated that when rifampin starts or stops, gradually changing rivaroxaban dose during the first few days would elevate the efficacy and safety of rivaroxaban.
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http://dx.doi.org/10.3389/fphar.2021.706781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342882PMC
July 2021

The Relationship of Mitral Annulus Shape at CT to Mitral Regurgitation after Transcatheter Aortic Valve Replacement.

Radiology 2021 10 27;301(1):93-102. Epub 2021 Jul 27.

From the Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu 610041.

Background There are conflicting results over the improvement rate and predictors of mitral regurgitation in patients undergoing transcatheter aortic valve replacement (TAVR). Purpose To define the cause, degree of improvement, and improvement predictors of moderate to severe mitral regurgitation in patients undergoing TAVR by using a simplified D-shaped mitral annulus model derived from multisection CT (MSCT). Materials and Methods This retrospective cohort study included 528 consecutive patients who underwent TAVR between April 2012 and October 2019. Patients with previous surgical aortic valve replacement and those with moderate or severe mitral stenosis were excluded. A total of 104 patients with moderate to severe mitral regurgitation met the inclusion criteria and were included in the final analysis. At least one grade reduction in the severity of mitral regurgitation was considered indicative of mitral regurgitation improvement after TAVR. Up to 5-year post-TAVR follow-up of mitral regurgitation improvement was evaluated. Mitral annular dimensions (annular area, circumference, and trigone-to-trigone, intercommissural, and anteroposterior distances) and annular calcification were assessed at MSCT with use of dedicated postprocessing software. Associations with mitral regurgitation improvement after TAVR were explored. Results A total of 104 patients with concomitant mitral regurgitation who underwent TAVR (mean age, 74 years ± 7; 61 men) were included in the study. Mitral regurgitation improved in 79 patients after TAVR and remained unchanged in the remaining 25 patients. Maximum improvement was observed in the 1st year after TAVR. D-shaped mitral annular parameters, including annular circumference (odds ratio [OR], 1.05; 95% CI: 1.01, 1.1; = .02) and trigone-to-trigone (OR, 1.2; 95% CI: 1.03, 1.39; = .02) and intercommissural (OR, 1.15; 95% CI: 1.02, 1.31; = .02) distances, were related to mitral regurgitation improvement. In addition, patients with coronary artery disease had greater improvement in mitral regurgitation after TAVR (OR, 0.17; 95% CI: 0.04, 0.76; = .02). Primary mitral regurgitation (OR, 5.1; 95% CI: 1.1, 24; = .04) and D-shaped annular circumference (OR, 1.06; 95% CI: 1, 1.11; = .04) were independent predictors of less mitral regurgitation improvement after TAVR. Conclusion Concomitant mitral regurgitation in patients undergoing transcatheter aortic valve replacement (TAVR) tends to improve after the procedure, with maximum improvement in the 1st year after TAVR. D-shaped annular circumference and primary mitral regurgitation were independent predictors of less mitral regurgitation improvement after TAVR. © RSNA, 2021 See also the editorial by Collins in this issue.
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http://dx.doi.org/10.1148/radiol.2021210267DOI Listing
October 2021

Bidirectional interconversion of microwave and light with thin-film lithium niobate.

Nat Commun 2021 Jul 22;12(1):4453. Epub 2021 Jul 22.

Department of Electrical Engineering, Yale University, New Haven, CT, USA.

Superconducting cavity electro-optics presents a promising route to coherently convert microwave and optical photons and distribute quantum entanglement between superconducting circuits over long-distance. Strong Pockels nonlinearity and high-performance optical cavity are the prerequisites for high conversion efficiency. Thin-film lithium niobate (TFLN) offers these desired characteristics. Despite significant recent progresses, only unidirectional conversion with efficiencies on the order of 10 has been realized. In this article, we demonstrate the bidirectional electro-optic conversion in TFLN-superconductor hybrid system, with conversion efficiency improved by more than three orders of magnitude. Our air-clad device architecture boosts the sustainable intracavity pump power at cryogenic temperatures by suppressing the prominent photorefractive effect that limits cryogenic performance of TFLN, and reaches an efficiency of 1.02% (internal efficiency of 15.2%). This work firmly establishes the TFLN-superconductor hybrid EO system as a highly competitive transduction platform for future quantum network applications.
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http://dx.doi.org/10.1038/s41467-021-24809-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298523PMC
July 2021

Left ventricular diastolic pressure gradient and outcome in advanced chronic kidney disease patients with preserved ejection fraction.

Int J Cardiovasc Imaging 2021 Sep 20;37(9):2663-2673. Epub 2021 Jul 20.

Department of Cardiology, West China Hospital of Sichuan University, 37 Guoxue Alley, Chengdu, 610041, Sichuan, China.

Assessment of left ventricular (LV) diastolic dysfunction is important in patients with chronic kidney disease (CKD). The early diastolic peak intraventricular pressure gradient (IVPG) has a vital role in diastolic function. Relative pressure imaging (RPI) is a new echocardiographic method to quantify IVPG. The purpose of this study was to analyze RPI-derived IVPG in advanced CKD patients with preserved LV ejection fraction. The study population consisted of 51 advanced CKD patients and 39 healthy controls. Patients were stratified by the evidence of heart failure with preserved ejection fraction (HFpEF) into HFpEF group (32 patients) and non-HFpEF group (19 patients). RPI analysis was used to determine the early diastolic LV relative pressure and pressure distribution. The total IVPG and segmental IVPGs corresponding to basal, mid, and apical part of the LV were calculated. Total IVPG, along with apical and mid IVPGs were all significantly reduced in HFpEF Group compared with non-HFpEF Group and controls (all P < 0.05). But no significant difference of total or segmental IVPGs was found between non-HFpEF Group and the controls. Additionally, apical IVPG < 0.02 mmHg/cm (Hazard ratio 9.82, 95 % confidence interval 2.01-48.01, P = 0.005) was the independent risk factor for the composite outcome (mortality and cardiovascular hospitalization) during a median follow-up of 24 months. Advanced CKD patients with HFpEF exhibited decreased apical and mid IVPG of the LV, and the severity of apical IVPG reduction correlated with poor outcome.
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http://dx.doi.org/10.1007/s10554-021-02339-4DOI Listing
September 2021

Dynamics of sediment phosphorus affected by mobile aeration: Pilot-scale simulation study in a hypereutrophic pond.

J Environ Manage 2021 Nov 16;297:113297. Epub 2021 Jul 16.

Chengdu Academy of Agricultural and Forestry Science, Chengdu, 610000, China.

Controlling the release of phosphorus (P) in sediments is important to prevent eutrophication and harmful algal blooms in water bodies. Here we explored the effect of mobile aerators on the control of P release from sediments in a eutrophic pond. The dissolved oxygen in the water body recovered significantly after six months of aeration, becoming 4.2-5.8 times higher than in the control. The pH and Eh values at the sediment-water interface considerably increased, while the concentration of soluble reactive phosphorus (SRP) in pore water significantly decreased, resulting in the alteration of SRP fluxes from 1.69 mg/m d to -53.49 mg/m d. Moreover, the inert P in sediments increased by 5.2% of the total P at the end of the study compared with the initial state, and the calcium-bound phosphorus (HCl-P) increased by 96.6%. However, although aeration reduced the concentration of SRP in the water column, the total P concentration was 2.45 times higher than that of the control, and the content of redox-sensitive P (BD-P) in the sediment also increased by 200%. Overall, although mobile aeration can maintain the microenvironment of the sediment interface and increase the inert P content in the sediment to reduce the P flux, it cannot reduce the risk of release of mobile P.
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http://dx.doi.org/10.1016/j.jenvman.2021.113297DOI Listing
November 2021

Cell heterogeneity, rather than the cell storage solution, affects the behavior of mesenchymal stem cells in vitro and in vivo.

Stem Cell Res Ther 2021 07 13;12(1):391. Epub 2021 Jul 13.

Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.

Background: Mesenchymal stem cells (MSCs) have to be expanded in vitro to reach a sufficient cell dose for the treatment of various diseases. During the process of expansion, some obstacles remain to be overcome. The purpose of this study was to investigate the effects of storage solutions and heterogeneity on the behavior of MSCs in vitro and in vivo.

Methods: Umbilical cord MSCs (UC-MSCs) of similar sizes within normal ranges were suspended in three different storage solutions, phosphate buffer solution, normal saline, and Dulbecco's modified Eagle medium. Then, the ultrastructure, viability, and safety of these cells were compared. Other two UC-MSC populations of different sizes were categorized based on their mean diameters. The ultrastructure, proliferation, immunosuppression, hepatic differentiation potential, and number of senescent cells were investigated and compared. The survival rates of mice after the infusion of UC-MSCs of different sizes were compared.

Results: For UC-MSCs suspended in different storage solutions, the cell apoptosis rates, ultrastructure, and survival rates of mice were similar, and no differences were observed. Cells with a diameter of 19.14 ± 4.89 μm were categorized as the larger UC-MSC population, and cells with a diameter of 15.58 ± 3.81 μm were categorized as the smaller population. The mean diameter of the larger UC-MSC population was significantly larger than that of the smaller UC-MSC population (p < 0.01). Smaller UC-MSCs had more powerful proliferation and immunosuppressive potential and a higher nucleus-cytoplasm ratio than those of large UC-MSCs. The number of cells positive for β-galactosidase staining was higher in the larger UC-MSC population than in the smaller UC-MSC population. The survival rates of mice receiving 1 × 10 or 2 × 10 smaller UC-MSCs were 100%, both of which were higher than those of mice receiving the same amounts of larger UC-MSCs (p < 0.01). The cause of mouse death was explored and it was found that some larger UC-MSCs accumulated in the pulmonary capillary in dead mice.

Conclusion: Different storage solutions showed no significant effects on cell behavior, whereas heterogeneity was quite prevalent in MSC populations and might limit cells application. Hence, it is necessary to establish a more precise standardization for culture-expanded MSCs.
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http://dx.doi.org/10.1186/s13287-021-02450-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278752PMC
July 2021

Erratum for Li et al., "Molecular Basis of the Versatile Regulatory Mechanism of HtrA-Type Protease AlgW from Pseudomonas aeruginosa".

mBio 2021 Aug 13;12(4):e0164021. Epub 2021 Jul 13.

Center of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan Universitygrid.13291.38 and Collaborative Innovation Center, Chengdu, China.

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http://dx.doi.org/10.1128/mBio.01640-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406303PMC
August 2021

Screening of the HBx transactivation domain interacting proteins and the function of interactor Pin1 in HBV replication.

Sci Rep 2021 07 8;11(1):14176. Epub 2021 Jul 8.

Department of Forensic Pathology, West China School of Preclinical and Forensic Medicine, Sichuan University, No. 17 Third Renmin Road North, Chengdu, 610041, People's Republic of China.

Hepatitis B virus (HBV) X protein (HBx) has been determined to play a crucial role in the replication and transcription of HBV, and its biological functions mainly depend on the interaction with other host proteins. This study aims at screening the proteins that bind to the key functional domain of HBx by integrated proteomics. Proteins that specifically bind to the transactivation domain of HBx were selected by comparing interactors of full-length HBx and HBx-D5 truncation determined by glutathione-S-transferase (GST) pull-down assay combined with mass spectrometry (MS). The function of HBx interactor Pin1 in HBV replication was further investigated by in vitro experiments. In this study, a total of 189 proteins were identified from HepG2 cells that specifically bind to the transactivation domain of HBx by GST pull-down and subsequent MS. After gene ontology (GO) analysis, Pin1 was selected as the protein with the highest score in the largest cluster functioning in protein binding, and also classified into the cluster of proteins with the function of structural molecule activity, which is of great potential to be involved in HBV life cycle. The interaction between Pin1 and HBx has been further confirmed by Ni-NTA pulldown assay, co-immunoprecipitation, and immunofluorescence microscopy. HBsAg and HBeAg levels significantly decreased in Pin1 expression inhibited HepG2.2.15 cells. Besides, the inhibition of Pin1 expression in HepG2 cells impeded the restored replication of HBx-deficient HBV repaired by ectopic HBx expression. In conclusion, our study identified Pin1 as an interactor binds to the transactivation domain of HBx, and suggested the potential association between Pin1 and the function of HBx in HBV replication.
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http://dx.doi.org/10.1038/s41598-021-93584-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266847PMC
July 2021

Tenofovir disoproxil fumarate in Chinese chronic hepatitis B patients: Results of a multicenter, double-blind, double-dummy, clinical trial at 96 weeks.

World J Clin Cases 2021 Jun;9(18):4690-4699

Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing 100034, China.

Background: Tenofovir disoproxil fumarate (TDF) is a prodrug of a nucleotide analogue. As an antiviral drug, TDF has been proposed in the first-line treatment of chronic hepatitis B (CHB). Qingzhong, a brand name of TDF, commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd., and Viread, another brand name of TDF, commercialized by GlaxoSmithKline, have both been approved by the State Food and Drug Administration, China.

Aim: To investigate the efficacy and safety of the two TDF agents in the treatment of Chinese CHB patients.

Methods: This trial was registered at ClinicalTrials.gov with the identifier number of NCT02287857. A total of 330 Chinese CHB patients, among which 232 were hepatitis B e antigen (HBeAg)-positive, were included in this 5-year-long, multicenter, double-blinded, double-dummy, randomized-controlled, non-inferiority phase III trial. The participants were initially randomized into two groups: Group A ( = 161), in which the participants received 300 mg Qingzhong once a day for 48 wk; and Group B, in which the participants received 300 mg Viread once a day for 48 wk. Starting from week 49, all the participants in Groups A and B received 300 mg Qingzhong once a day until the 96 week. In this study, the primary endpoint was the decrease in plasma level of hepatitis B virus (HBV) DNA at the 96 week, while the secondary endpoints were suppression of HBV replication, alanine aminotransferase (ALT) normalization, HBeAg loss, and HBeAg seroconversion rates.

Results: For the participants with HBeAg-positive CHB, the decrease in mean HBV DNA level relative to the baseline value was comparable between Groups A and B (5.77 5.73 log IU/mL, > 0.05) at the 96 week. In addition, similar percentages of HBeAg-positive participants in the two groups exhibited undetectable levels of HBV DNA, HBeAg loss, and HBeAg seroconversion (71.05% 77.97%, 31.00% 27.27%, and 20.22% 15.79%, respectively, in Group A Group B; > 0.05). For the participants with HBeAg-negative CHB, the decrease in mean HBV DNA level relative to the baseline value was also comparable between Groups A and B (4.46 4.70 log IU/mL, > 0.05) at the 96 week. In addition, similar percentages of HBeAg-negative participants in the two groups exhibited undetectable levels of HBV DNA (87.23% 94.12% in Group A Group B, respectively; > 0.05). Finally, similar percentages of CHB patients (HBeAg-positive or HBeAg-negative) in the two groups exhibited normalization of ALT (80.14% 84.57% in Group A Group B, respectively; > 0.05), and similar incidences of adverse events were observed (106 104 in Group A Group B, respectively; > 0.05).

Conclusion: Both Qingzhong and Viread are effective and safe in the treatment of Chinese CHB patients according to the results of our clinical trial.
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http://dx.doi.org/10.12998/wjcc.v9.i18.4690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223849PMC
June 2021

3-year Treatment of Tenofovir Alafenamide . Tenofovir Disoproxil Fumarate for Chronic HBV Infection in China.

J Clin Transl Hepatol 2021 Jun 28;9(3):324-334. Epub 2021 Apr 28.

The Sixth People's Hospital of Shenyang, Shenyang, Liaoning, China.

Background And Aims: Tenofovir alafenamide (TAF) has similar efficacy to tenofovir disoproxil fumarate (TDF) but with improved renal and bone safety in chronic hepatitis B patients studied outside of China. We report 3-year results from two phase 3 studies with TAF in China (Clinicaltrials.gov: NCT02836249 and NCT02836236).

Methods: Chinese hepatitis B e antigen (HBeAg)-positive and -negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks (3 years). Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis.

Results: Of the 334 patients (180 HBeAg-positive and 154 HBeAg-negative) randomized and treated, baseline characteristics were similar between groups. The overall mean age was 38 years and 73% were male. The mean HBV DNA was 6.4 log IU/mL. The median alanine aminotransferase was 88 U/L, and 37% had a history of antiviral use. At week 144, the proportion with HBV DNA <29 IU/mL was similar among the two groups, with TAF at 83% vs. TDF at 79%, and TAF at 93% vs. TDF at 92% for the HBeAg-positive and -negative patients, respectively. In each study, higher proportions of TAF than TDF patients showed normalized alanine aminotransferase (via the American Association for the Study of Liver Diseases and the China criteria) and showed loss of HBsAg; meanwhile, the HBeAg seroconversion rates were similar. Treatment was well-tolerated among the TAF patients, who showed a smaller median decline in creatinine clearance (-0.4 vs. -3.2 mL/min; =0.014) and less percentage change in bone mineral density vs. TDF at hip (-0.95% vs. -1.93%) and spine (+0.35% vs. -1.40%).

Conclusions: In chronic hepatitis B patients from China, TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.
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http://dx.doi.org/10.14218/JCTH.2020.00145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237145PMC
June 2021
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