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  1. WHO Solidarity Trial Consortium, Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, et al.
    N Engl J Med, 2021 Feb 11;384(6):497-511.
    PMID: 33264556 DOI: 10.1056/NEJMoa2023184
    BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19).

    METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry.

    RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration.

    CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).

  2. Ling W, Liew G, Li Y, Hao Y, Pan H, Wang H, et al.
    Adv Mater, 2018 Jun;30(23):e1800917.
    PMID: 29633379 DOI: 10.1002/adma.201800917
    The combination of novel materials with flexible electronic technology may yield new concepts of flexible electronic devices that effectively detect various biological chemicals to facilitate understanding of biological processes and conduct health monitoring. This paper demonstrates single- or multichannel implantable flexible sensors that are surface modified with conductive metal-organic frameworks (MOFs) such as copper-MOF and cobalt-MOF with large surface area, high porosity, and tunable catalysis capability. The sensors can monitor important nutriments such as ascorbicacid, glycine, l-tryptophan (l-Trp), and glucose with detection resolutions of 14.97, 0.71, 4.14, and 54.60 × 10-6 m, respectively. In addition, they offer sensing capability even under extreme deformation and complex surrounding environment with continuous monitoring capability for 20 d due to minimized use of biological active chemicals. Experiments using live cells and animals indicate that the MOF-modified sensors are biologically safe to cells, and can detect l-Trp in blood and interstitial fluid. This work represents the first effort in integrating MOFs with flexible sensors to achieve highly specific and sensitive implantable electrochemical detection and may inspire appearance of more flexible electronic devices with enhanced capability in sensing, energy storage, and catalysis using various properties of MOFs.
  3. Tackett S, Wright S, Lubin R, Li J, Pan H
    Med Educ, 2017 Mar;51(3):280-289.
    PMID: 27896846 DOI: 10.1111/medu.13120
    OBJECTIVE: To assess whether favourable perceptions of the learning environment (LE) were associated with better quality of life, less burnout and more empathy across three undergraduate medical education programmes in Israel, Malaysia and China.

    METHODS: Cross-sectional surveys were administered at the end of the 2013-2014 academic year at three medical schools: Technion American Medical Students Program (TAMS) in Israel, Perdana University-Royal College of Surgeons in Ireland School of Medicine (PURCSI) in Malaysia and Peking Union Medical College (PUMC) in China. LE perceptions were assessed using the Johns Hopkins Learning Environment Scale (JHLES). Well-being was assessed using validated items for quality of life and the depersonalisation and emotional exhaustion domains of burnout. The 20-item Jefferson Empathy Scale assessed empathy. Statistical analyses included bivariate regressions and multivariate regressions that adjusted for gender, school, class year and perceived academic rank.

    RESULTS: Overall, 400/622 (64.3%) students responded, with the following rates by site: TAMS 92/121 (76.0%), PURCSI 160/198 (80.1%) and PUMC 148/303 (48.8%). In multivariate models, favourable overall LE perceptions were associated with higher odds of good quality of life (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.8-5.8; p < 0.001) and lower odds of emotional exhaustion (OR, 0.34; 95% CI, 0.24-0.50; p < 0.001) and depersonaliation (OR, 0.30; 95% CI, 0.24-0.37; p = 0.001). 'Community of Peers', one of seven factors in the JHLES, was the only one to be independently associated with better quality of life and less emotional exhaustion and depersonalisation. After adjusting for covariates, there was not a statistically significant association between overall LE and empathy (OR, 1.4; 95% CI, 0.91-2.2; p = 0.12).

    CONCLUSIONS: Students' LE perceptions are closely associated with their well-being, and fostering peer community may hold promise for enhancing quality of life and protecting against burnout. Across these three settings, LE and empathy were not closely related, suggesting that any influence of learning environment on empathy would be modest.
  4. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  5. Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, et al.
    Ann Oncol, 2015 Sep;26(9):1883-1889.
    PMID: 26105600 DOI: 10.1093/annonc/mdv270
    BACKGROUND: The phase III, randomized, open-label ENSURE study (NCT01342965) evaluated first-line erlotinib versus gemcitabine/cisplatin (GP) in patients from China, Malaysia and the Philippines with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).

    PATIENTS AND METHODS: Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.

    RESULTS: A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.

    CONCLUSION: These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).

  6. Xi B, Zong X, Kelishadi R, Hong YM, Khadilkar A, Steffen LM, et al.
    Circulation, 2016 Jan 26;133(4):398-408.
    PMID: 26671979 DOI: 10.1161/CIRCULATIONAHA.115.017936
    Several distributions of country-specific blood pressure (BP) percentiles by sex, age, and height for children and adolescents have been established worldwide. However, there are no globally unified BP references for defining elevated BP in children and adolescents, which limits international comparisons of the prevalence of pediatric elevated BP. We aimed to establish international BP references for children and adolescents by using 7 nationally representative data sets (China, India, Iran, Korea, Poland, Tunisia, and the United States).
  7. Xu RH, Zhang Y, Pan H, Feng J, Zhang T, Liu T, et al.
    Lancet Gastroenterol Hepatol, 2021 12;6(12):1015-1024.
    PMID: 34626550 DOI: 10.1016/S2468-1253(21)00313-7
    BACKGROUND: In the global phase 3 RAINBOW study, ramucirumab plus paclitaxel significantly improved overall survival compared with placebo plus paclitaxel in patients with advanced gastric or gastro-oesophageal junction (GEJ) adenocarcinoma. RAINBOW-Asia, a bridging study with similar design to RAINBOW, aimed to evaluate the efficacy and safety of ramucirumab plus paclitaxel for advanced gastric or GEJ adenocarcinoma in Asian, predominantly Chinese, patients.

    METHODS: RAINBOW-Asia was a randomised, double-blind, placebo-controlled, phase 3 trial done at 32 centres in China, Malaysia, the Philippines, and Thailand. Adult patients (≥18 years) with metastatic or locally advanced, unresectable gastric or GEJ adenocarcinoma who previously received fluoropyrimidine-platinum-based chemotherapy were randomly assigned with a centralised interactive web response system in a 2:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15 plus paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 of every 28-day cycle. Randomisation was stratified by Eastern Cooperative Oncology Group performance status and presence of peritoneal metastases. The co-primary endpoints were progression-free survival and overall survival. Efficacy analyses were done in the intention-to-treat population, and safety analysis included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02898077, and has been completed.

    FINDINGS: Between March 2, 2017, and June 30, 2020, 440 patients were randomly assigned to receive ramucirumab plus paclitaxel (n=294) or placebo plus paclitaxel (n=146). Median progression-free survival was 4·14 months (95% CI 3·71-4·30) in the ramucirumab plus paclitaxel group compared with 3·15 months (2·83-4·14) in the placebo plus paclitaxel group (hazard ratio [HR] 0·765, 95% CI 0·613-0·955, p=0·0184). Median overall survival was 8·71 months (95% CI 7·98-9·49) in the ramucirumab plus paclitaxel group and 7·92 months (6·31-9·10) in the placebo plus paclitaxel group (HR 0·963, 95% CI 0·771-1·203, p=0·7426). The most common grade 3 or worse treatment-emergent adverse events were decreased neutrophil count (159 [54%] of 293 patients in the ramucirumab plus paclitaxel group vs 56 [39%] of 145 in the placebo plus paclitaxel group), decreased white blood cell count (127 [43%] vs 42 [29%]), anaemia (46 [16%] vs 24 [17%]), hypertension (21 [7%] vs nine [6%]), and febrile neutropenia (18 [6%] vs one [<1%]).

    INTERPRETATION: These findings, along with the results from RAINBOW, support the use of ramucirumab plus paclitaxel as second-line therapy in a predominantly Chinese population with advanced gastric or GEJ adenocarcinoma.

    FUNDING: Eli Lilly and Company, USA.

    TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

  8. Deng T, Shi W, Wong ZM, Wu G, Yang X, Zheng JC, et al.
    J Phys Chem Lett, 2021 Jul 29;12(29):6934-6940.
    PMID: 34282908 DOI: 10.1021/acs.jpclett.1c01731
    The connection between electronic structures of metal-organic frameworks (MOFs) and their building subunits is a key cornerstone for rational MOF material design. Some two-dimensional conjugated MOFs were reported to be topological insulators. However, many of them are not intrinsic as the Fermi levels are far from the topological gaps. The subunit-to-MOF electronic orbital correspondence should be established to bridge their chemical structure and physical properties, thus understanding the design rules toward intrinsic topological insulators. Herein we reveal the fundamental role of the subunit-to-MOF symmetry relation in determining their orbital interaction and hybridization and, consequently, topological characteristics. In particular, such honeycomb-kagome MOFs possess delocalized symmetry-enforced nonbonding electronic states with the topological spin-orbit gap. The nonbonding nature of these states allows tailored band structure modulation through molecular structure and strain engineering, with the potential realization of an intrinsic metal-organic topological insulator.
  9. Dai Z, Dang M, Zhang W, Murugan S, Teh SW, Pan H
    Artif Cells Nanomed Biotechnol, 2019 Dec;47(1):1898-1907.
    PMID: 31066314 DOI: 10.1080/21691401.2019.1573183
    Hydroxyapatite (HAP) is a significant bone mineral that establishes bone strength. HAP composites in combination with biodegradable and bioactive polymer poly xylitol sebacic adipate (PXSA) would result in a constant release at target sites. Numerous studies have shown that vitamin K (VK) might possess a vital function in bone metabolism. The purpose of the present study was to inspect the synthesized composite HAP/PXSA/VK in developing polymeric biomaterials composite for the application of bone tissue regeneration. FTIR, X-ray diffraction, SEM and TEM techniques were applied to characterize the prepared composites. The release of VK from the HAP/PXSA/VK composite was evidenced through UV-Vis spectroscopy. In vitro studies proved that the HAP/PXSA/VK composite is appropriate for mesenchymal stem cell culture. Compared to pure HAP prepared following the same method, HAP/PXSA/VK composite provided favourable microstructures and good biodegradation distinctiveness for the application of tissue engineering, as well as tissue in-growth characteristics and improved scaffold cell penetration. This work reveals that the HAP/PXSA/VK composites have the potential for applications in bone tissue engineering.
  10. Hu L, Wang Y, Pan H, Kadir K, Wen J, Li S, et al.
    Stem Cell Res Ther, 2021 03 16;12(1):185.
    PMID: 33726822 DOI: 10.1186/s13287-021-02253-5
    OBJECTIVES: This study aims to investigate whether apoptosis repressor with caspase recruitment domain (ARC) could promote survival and enhance osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs).

    MATERIALS AND METHODS: The lentivirus transfection method was used to establish ARC-overexpressing BMSCs. The CCK-8 method was used to detect cell proliferation. The BD Pharmingen™ APC Annexin V Apoptosis Detection kit was used to detect cell apoptosis. The osteogenic capacity was investigated by OCN immunofluorescence staining, ALP analysis, ARS assays, and RT-PCR analysis. Cells were seeded into calcium phosphate cement (CPC) scaffolds and then inserted subcutaneously into nude mice and the defect area of the rat calvarium. Histological analysis was conducted to evaluate the in vivo cell apoptosis and new bone formation of the ARC-overexpressing BMSCs. RNA-seq was used to detect the possible mechanism of the effect of ARC on BMSCs.

    RESULTS: ARC promoted BMSC proliferation and inhibited cell apoptosis. ARC enhanced BMSC osteogenic differentiation in vitro. An in vivo study revealed that ARC can inhibit BMSC apoptosis and increase new bone formation. ARC regulates BMSCs mainly by activating the Fgf-2/PI3K/Akt pathway.

    CONCLUSIONS: The present study suggests that ARC is a powerful agent for promoting bone regeneration of BMSCs and provides a promising method for bone tissue engineering.

  11. Woodward M, Ramasubramanian V, Kamarulzaman A, Tantawichien T, Wang M, Song JY, et al.
    Clin Interv Aging, 2023;18:869-880.
    PMID: 37284594 DOI: 10.2147/CIA.S406601
    The impact of vaccinating the older population against vaccine-preventable diseases in terms of health, social and economic benefits has been increasingly recognised. However, there is a gap in the utilisation of vaccines worldwide. The population is ageing at an unprecedented pace in the Asia-Pacific (APAC) region, with the number of persons older than 65 years set to double by 2050 to around 1.3 billion. More than 18% of the population in Japan, Hong Kong, and China is over the age of 65 years. This highlights the importance of prioritising resources to address societal obligations toward the needs of the ageing generation. This review provides an overview of the challenges to adult vaccination in APAC, drivers to increase vaccination coverage, vaccination insights gained through the COVID-19 pandemic, and potential measures to increase the uptake of adult vaccines in the region.
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