Search

Abstract The size and axial alignment of prostheses, when planned during total knee replacement (TKA) are critical for recovery of knee function and improvement of knee pain symptoms. This research aims to study the effect of artificial intelligence (AI)-based preoperative three dimensional (3D) planning technology on prosthesis size and axial alignment planning in TKA, and to compare its advantages with two dimensional (2D) X-ray template measurement technology. A total of 60 patients with knee osteoarthritis (KOA) who underwent TKA for the first time were included in the AI (n = 30) and 2D (n = 30) groups. The preoperative and postoperative prosthesis size, femoral valgus correction angle (VCA) and hip-knee-ankle angle (HKA) were recorded and compared between the two groups. The results of the University of Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the American Knee Association Score (AKS) were evaluated before surgery, 3 months, 6 months, and 12 months after surgery. The accuracy of prosthesis size, VCA and HKA prediction in AI group was significantly higher than that in 2D group (P

Ovarian cancer is a common cancer for females, and the incidence and mortality rates are on the rise. Many treatment strategies have been developed for ovarian cancer, including chemotherapy and immunotherapy, but they are often ineffective and prone to drug resistance. Protein ubiquitination is an important class of post-translation modifications that have been found to be associated with various human diseases and cancer development. Recent studies have revealed that protein ubiquitination is involved in the progression of ovarian cancer and plays an important role in the tumor immune process. Moreover, the combination of ubiquitinase/deubiquitinase inhibitors and cancer immunotherapy approaches can effectively reduce treatment resistance and improve treatment efficacy, which provides new ideas for cancer treatment. Herein, we review the role of protein ubiquitination in relation to ovarian cancer immunotherapy and recent advances in the use of ubiquitinase/deubiquitinase inhibitors in combination with cancer immunotherapy.

BackgroundShared decision-making (SDM) on antibiotic therapy may improve antibiotic use in tertiary hospitals, but hospitalised patients are apprehensive about being involved in it. Understanding the facilitators and barriers to SDM can inform the design and implementation of interventions to empower these patients to engage in SDM on their antibiotic therapies.MethodsWe conducted qualitative interviews with 23 adult patients purposively sampled with maximum variation from the three largest tertiary-care hospitals in Singapore (April 2019─October 2020). Thematic analysis was conducted using the Theoretical Domains Framework and Capability, Opportunity, Motivation, Behaviour (COM-B) model to identify areas for intervention.ResultsHospitalised patients lacked comprehensive knowledge of their antibiotic therapies and the majority did not have the skills to actively query their doctors about them. There was a lack of opportunities to meet and interact with doctors, and patients were less motivated to engage in SDM if they had a self-perceived paternalistic relationship with doctors, trusted their doctors to provide the best treatment, and had self-perceived poor knowledge to engage in SDM. To empower these patients, they should first be educated with antibiotic knowledge. Highlighting potential side effects of antibiotics could motivate them to ask questions about their antibiotic therapies. Environment restructuring, as facilitated by nurses and visual cues to nudge conversations, could create opportunities for interactions and motivating patients into SDM on their antibiotic therapies.ConclusionEducation and environmental restructuring should be explored to empower hospitalised patients to engage in SDM on their antibiotic therapies.

Abstract Triple‐negative breast cancer (TNBC), the most aggressive subtype of breast cancer, has a poor prognosis and lacks effective treatment strategies. Here, the study discovered that TNBC shows a decreased expression of epithelial transcription factor ovo‐like 2 (OVOL2). The loss of OVOL2 promotes fatty acid oxidation (FAO), providing additional energy and NADPH to sustain stemness characteristics, including sphere‐forming capacity and tumor initiation. Mechanistically, OVOL2 not only suppressed STAT3 phosphorylation by directly inhibiting JAK transcription but also recruited histone deacetylase 1 (HDAC1) to STAT3, thereby reducing the transcriptional activation of downstream genes carnitine palmitoyltransferase1 (CPT1A and CPT1B). PyVT‐Ovol2 knockout mice develop a higher number of primary breast tumors with accelerated growth and increased lung‐metastases. Furthermore, treatment with FAO inhibitors effectively reduces stemness characteristics of tumor cells, breast tumor initiation, and metastasis, especially in OVOL2‐deficient breast tumors. The findings suggest that targeting JAK/STAT3 pathway and FAO is a promising therapeutic strategy for OVOL2‐deficient TNBC.

After more than four decades of China’s reform and opening up, many family businesses in China are welcoming the peak of trans-generational inheritance. Therefore, more research is needed to help the second-generation successors avoid the potential negative effect of trans-generational conflicts and keep and maintain the sustainable development of their family businesses. To fill these gaps in the literature, this paper explores the impact of trans-generational conflicts on trans-generational entrepreneurial performance and investigates the moderating role of first-generation entrepreneurs’ business and social networks. Based on a survey data captured from the 221 matched responses from founder and second-generation successors dyads in China, we found that both cognitive and process conflicts have negative effects on trans-generational entrepreneurial performance, and process conflict has a greater negative impact than cognitive conflict. Furthermore, we found that the first-generation entrepreneurs’ business and social networks independently alleviate the negative impact of cognitive conflict on trans-generational entrepreneurial performance. By examining the three-way inaction effect, we also found that the negative effect of process conflict on trans-generational entrepreneurial performance is alleviated. Theoretical and managerial implications are also provided.

Abstract Several lines of evidence support the involvement of transcriptomic and epigenetic mechanisms in the brain structural deficits of major depressive disorder (MDD) separately. However, research in these two areas has remained isolated. In this study, we proposed an integrative strategy that combined neuroimaging, brain-wide gene expression, and peripheral DNA methylation data to investigate the genetic basis of gray matter abnormalities in MDD. The MRI T1-weighted images and Illumina 850 K DNA methylation microarrays were obtained from 269 patients and 416 healthy controls, and brain-wide transcriptomic data were collected from Allen Human Brain Atlas. The between-group differences in gray matter volume (GMV) and differentially methylated CpG positions (DMPs) were examined. The genes with their expression patterns spatially related to GMV changes and genes with DMPs were overlapped and selected. Using principal component regression, the associations between DMPs in overlapped genes and GMV across individual patients were investigated, and the region-specific correlations between methylation status and gene expression were examined. We found significant associations between the decreased GMV and DMPs methylation status in the anterior cingulate cortex, inferior frontal cortex, and fusiform face cortex regions. These DMPs genes were primarily enriched in the neurodevelopmental and synaptic transmission process. There was a significant negative correlation between DNA methylation and gene expression in genes associated with GMV changes of the frontal cortex in MDD. Our findings suggest that GMV abnormalities in MDD may have a transcriptomic and epigenetic basis. This imaging-transcriptomic-epigenetic integrative analysis provides spatial and biological links between cortical morphological deficits and peripheral epigenetic signatures in MDD.

In order to study the geochemical characteristics and sedimentary environment of the Middle Jurassic coal seam in the southwestern margin of the North China Plate, taking the coal of Yima Formation in Yima Basin as the research object to study the geochemical characteristics and sedimentary environment of Middle Jurassic coal seams in the southwest margin of the North China plate, based on the data from X-ray fluorescence spectrometer and plasma mass spectrometer. The results show that: The content of major element of SiO2, P2O5 and K2O are significantly higher, while the content of Al2O3 is lower compared with Chinese coals. Enrichment of Cs and deficit of Sb, Nb, Ta, Zr and Hf in trace elements. The rare earth elements are slightly enriched as a whole, with negative Eu anomalies and positive Ce anomalies, indicating that the coal seam was not affected by magma, hydrothermal and seawater, and the provenance is mainly terrigenous clastic. It shows that the coal forming environment in reductive environment, and the whole coal forming period is in semi-arid climate environment by the analysis of Th/U, V/ (V+Ni), Ce anomaly, Sr/Cu and climate index.

EGFR is aberrantly activated in many cancer types. Here the authors show that small GTPase ARF6 mediates the trafficking of palmitoylated EGFR from Golgi to plasma membrane and the blockade of this sorting system inhibits the growth of EGFR overexpression tumours.

Abstract We assessed the preferences and trade-offs for social interactions, incentives, and being traced by a digital contact tracing (DCT) tool post lockdown in Singapore by a discrete choice experiment (DCE) among 3839 visitors of a large public hospital in Singapore between July 2020 – February 2021. Respondents were sampled proportionately by gender and four age categories (21 – 80 years). The DCE questionnaire had three attributes (1. Social interactions, 2. Being traced by a DCT tool, 3. Incentives to use a DCT tool) and two levels each. Panel fixed conditional logit model was used to analyse the data. Respondents were more willing to trade being traced by a DCT tool for social interactions than incentives and unwilling to trade social interactions for incentives. The proportion of respondents preferring no incentives and could only be influenced by their family members increases with age. Among proponents of monetary incentives, the preferred median value for a month’s usage of DCT tools amounted to S$10 (USD7.25) and S$50 (USD36.20) for subsidies and lucky draw. In conclusion, DCE can be used to elicit profile-specific preferences to optimize the uptake of DCT tools during a pandemic. Social interactions are highly valued by the population, who are willing to trade them for being traced by a DCT tool during the COVID-19 pandemic. Although a small amount of incentive is sufficient to increase the satisfaction of using a DCT tool, incentives alone may not increase DCT tool uptake.

Summary: Preadipocyte determination expanding the pool of preadipocytes is a vital process in adipocyte hyperplasia, but the molecular mechanisms underlying this process are yet to be elucidated. Herein, SRY-related HMG box transcription factor 4 (SOX4) was identified as a critical target in response to BMP4- and TGFβ-regulated preadipocyte determination. SOX4 deficiency is sufficient to promote preadipocyte determination in mesenchymal stem cells (MSCs) and acquisition of preadipocyte properties in nonadipogenic lineages, while its overexpression impairs the adipogenic capacity of preadipocytes and converts them into nonadipogenic lineages. Mechanism studies indicated that SOX4 activates and cooperates with LEF1 to retain the nuclear localization of β-catenin, thus mediating the crosstalk between TGFβ/BMP4 signaling pathway and Wnt signaling pathway to regulate the preadipocyte determination. In vivo studies demonstrated that SOX4 promotes the adipogenic-nonadipogenic conversion and suppresses the adipocyte hyperplasia. Together, our findings highlight the importance of SOX4 in regulating the adipocyte hyperplasia in obesity.

BackgroundThe misuse and overuse of antibiotics contribute to the acceleration of antimicrobial resistance (AMR), but public knowledge on appropriate antibiotic use and AMR remained low despite ongoing health promotion efforts. App gamification has gained traction in recent years for health promotion and to affect change in health behaviors. Hence, we developed an evidence-based serious game app “SteWARdS Antibiotic Defence” to educate the public on appropriate antibiotic use and AMR and address knowledge gaps. ObjectiveWe aim to evaluate the effectiveness of the “SteWARdS Antibiotic Defence” app in improving the knowledge of, attitude toward, and perception (KAP) of appropriate antibiotic use and AMR among the public. The primary objective is to assess the changes in KAP of antibiotic use and AMR in our participants, while the secondary objectives are to assess the extent of user engagement with the app and the level of user satisfaction in using the app. MethodsOur study is a parallel 2-armed randomized controlled trial with a 1:1 allocation. We plan to recruit 400 participants (patients or their caregivers) aged 18-65 years from government-funded primary care clinics in Singapore. Participants are randomized in blocks of 4 and into the intervention or control group. Participants in the intervention group are required to download the “SteWARdS Antibiotic Defence” app on their smartphones and complete a game quest within 2 weeks. Users will learn about appropriate antibiotic use and effective methods to recover from uncomplicated upper respiratory tract infections by interacting with the nonplayer characters and playing 3 minigames in the app. The control group will not receive any intervention. ResultsThe primary study outcome is the change in participants’ KAP toward antibiotic use and AMR 6-10 weeks post intervention or 6-10 weeks from baseline for the control group (web-based survey). We will also assess the knowledge level of participants immediately after the participant completes the game quest (in the app). The secondary study outcomes are the user engagement level (tracked by the app) and satisfaction level of playing the game (via the immediate postgame survey). The satisfaction survey will also collect participants’ feedback on the game app. ConclusionsOur proposed study provides a unique opportunity to assess the effectiveness of a serious game app in public health education. We anticipate possible ceiling effects and selection bias in our study and have planned to perform subgroup analyses to adjust for confounding factors. The app intervention will benefit a larger population if it is proven to be effective and acceptable to users. Trial RegistrationClinicalTrials.gov NCT05445414; https://clinicaltrials.gov/ct2/show/NCT05445414 International Registered Report Identifier (IRRID)DERR1-10.2196/45833

ABSTRACT: Objectives: Following the emergence of the Delta variant of SARS-CoV-2 in Singapore, our hospital experienced a Delta-linked ward cluster. In this study, we review the enhanced strategies in preventing nosocomial transmission of COVID-19 following widespread community transmission of the Delta variant. Methods: We conducted a cohort study on exposures to unexpected COVID-19 cases for which contact tracing was initiated from June 2021 to October 2021. Strategies evaluated included upgraded personal protective equipment (PPE) and rostered routine testing (RRT) for staff and patients, surveillance of staff with acute respiratory illness (ARI), and expanded quarantining and testing for contacts of identified cases. Results: From 193 unexpected COVID-19 exposures, 2,573 staff, 542 patients, and 128 visitor contacts were traced. Four staff contacts subsequently had SARS-CoV-2 infection. Two were likely from exposure in community settings, whereas 2 had exposure to the same COVID-19 positive staff in the hospital, forming the only hospital cluster. One inpatient had a nosocomial infection, possibly from visitors. The SARS-CoV-2 detection rate among staff was 0.3% (of 11,200 staff) from biweekly RRT and 2.5% (of 3,675 staff) from ARI surveillance. Conclusion: Enhanced hospital measures, including upgraded PPE and RRT for staff and patients, staff sickness surveillance, and more rigorous management of contacts of COVID-19 cases, were likely to have reduced nosocomial transmission amid the Delta variant.

Flowering time is an important agronomic trait in cabbage (Brassica oleracea L. var. capitata), but the molecular regulatory mechanism underlying flowering time regulation in cabbage remains unclear. In this study, transcriptome analysis was performed using two sets of cabbage materials: (1) the early-flowering inbred line C491 (P1) and late-flowering inbred line B602 (P2), (2) the early-flowering individuals F2-B and late-flowering individuals F2-NB from the F2 population. The analysis revealed 9508 differentially expressed genes (DEGs) common to both C491_VS_ B602 and F2-B_VS_F2-NB. The Kyoto Encyclopedia of Genes and Genomes (KEGGs) analysis showed that plant hormone signal transduction and the MAPK signaling pathway were mainly enriched in up-regulated genes, and ribosome and DNA replication were mainly enriched in down-regulated genes. We identified 321 homologues of Arabidopsis flowering time genes (Ft) in cabbage. Among them, 25 DEGs (11 up-regulated and 14 down-regulated genes) were detected in the two comparison groups, and 12 gene expression patterns closely corresponded with the different flowering times in the two sets of materials. Two genes encoding MADS-box proteins, Bo1g157450 (BoSEP2-1) and Bo5g152700 (BoSEP2-2), showed significantly reduced expression in the late-flowering parent B602 compared with the early-flowering parent C491 via qRT-PCR analysis, which was consistent with the RNA-seq data. Next, the expression levels of Bo1g157450 (BoSEP2-1) and Bo5g152700 (BoSEP2-2) were analyzed in two other groups of early-flowering and late-flowering inbred lines, which showed that their expression patterns were consistent with those in the parents. Sequence analysis revealed that three and one SNPs between B602 and C491 were identified in Bo1g157450 (BoSEP2-1) and Bo5g152700 (BoSEP2-2), respectively. Therefore, BoSEP2-1 and BoSEP2-2 were designated as candidates for flowering time regulation through a potential new regulatory pathway. These results provide new insights into the molecular mechanisms underlying flowering time regulation in cabbage.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide due to a high rate of tumour metastasis and disease recurrence. In physiological conditions, tetraspanins interact with specific partner proteins in tetraspanin‐enriched microdomains and regulate their subcellular localization and function. However, the function of Tspan5 in pathological processes, particularly in cancer biology and its clinical significance, are still unclear. Here, we describe that a high expression of Tspan5 is significantly associated with some clinicopathological features including invasive length, vascular invasion, clinical stage and poor overall survival of HCC patients. Alterations of Tspan5 expression by lentivirus transductions in HCC cells demonstrated that Tspan5 promotes wound healing and cell migration in vitro and tumour metastasis of HCC cells in vivo. Mechanistic studies revealed that Tspan5 promoted cell migration and tumour metastasis by increasing the enzymatic maturation of ADAM10 and activating Notch signalling via the increase of the cleavage of the Notch1 receptor catalysed by the γ‐secretase complex. Activation of Notch signalling by Tspan5 was shown further to enhance the epithelial–mesenchymal transition (EMT) and actin skeleton rearrangement of tumour cells. In clinical HCC samples, Tspan5 expression is strongly correlated with many key molecules acting in Notch signalling and EMT, highlighting the role of Tspan5 in the regulation of Notch signalling, EMT and tumour metastasis of HCC. Our findings provide new insights into the mechanism of tumour metastasis and disease progression of HCC and may facilitate the development of novel clinical intervention strategies against HCC.

Abstract Background Singapore’s healthcare system presents an ideal context to learn from diverse public and private operational models and funding systems. Aim To explore processes underpinning decision-making for antibiotic prescribing, by considering doctors’ experiences in different primary care settings. Methods Thirty semi-structured interviews were conducted with 17 doctors working in publicly funded primary care clinics (polyclinics) and 13 general practitioners (GP) working in private practices (solo, small and large). Data were analysed using applied thematic analysis following realist principles, synthesised into a theoretical model, informing solutions to appropriate antibiotic prescribing. Results Given Singapore’s lack of national guidelines for antibiotic prescribing in primary care, practices are currently non-standardised. Themes contributing to optimal prescribing related first and foremost to personal valuing of reduction in antimicrobial resistance (AMR) which was enabled further by organisational culture creating and sustaining such values, and if patients were convinced of these too. Building trusting patient-doctor relationships, supported by reasonable patient loads among other factors were consistently observed to allow shared decision-making enabling optimal prescribing. Transparency and applying data to inform practice was a minority theme, nevertheless underpinning all levels of optimal care delivery. These themes are synthesised into the VALUE model proposed for guiding interventions to improve antibiotic prescribing practices. These should aim to reinforce intrapersonal V alues consistent with prioritising AMR reduction, and A ligning organisational culture to these by leveraging standardised guidelines and interpersonal intervention tools. Such interventions should account for the wider systemic constraints experienced in publicly funded high patient turnover institutions, or private clinics with transactional models of care. Thus, ultimately a focus on L iaison between patient and doctor is crucial. For instance, building in adequate consultation time and props as discussion aids, or quick turnover communication tools in time-constrained settings. Message consistency will ultimately improve trust, helping to enable shared decision-making. Lastly, U se of monitoring data to track and E valuate antibiotic prescribing using meaningful indicators, that account for the role of shared decision-making can also be leveraged for change. Conclusions These VALUE dimensions are recommended as potentially transferable to diverse contexts, and the model as implementation tool to be tested empirically and updated accordingly.

Abstract Schizophrenia (SZ) is a neurodevelopmental disorder. There remain significant gaps in understanding the neural trajectory across development in SZ. A major research focus is to clarify the developmental functional changes of SZ and to identify the specific timing, the specific brain regions, and the underlying mechanisms of brain alterations during SZ development. Regional homogeneity (ReHo) characterizing brain function was collected and analyzed on humans with SZ (hSZ) and healthy controls (HC) cross-sectionally, and methylazoxymethanol acetate (MAM) rats, a neurodevelopmental model of SZ, and vehicle rats longitudinally from adolescence to adulthood. Metabolomic and proteomic profiling in adult MAM rats and vehicle rats was examined and bioanalyzed. Compared to HC or adult vehicle rats, similar ReHo alterations were observed in hSZ and adult MAM rats, characterized by increased frontal (medial prefrontal and orbitofrontal cortices) and decreased posterior (visual and associated cortices) ReHo. Longitudinal analysis of MAM rats showed aberrant ReHo patterns as decreased posterior ReHo in adolescence and increased frontal and decreased posterior ReHo in adulthood. Accordingly, it was suggested that the visual cortex was a critical locus and adolescence was a sensitive window in SZ development. In addition, metabolic and proteomic alterations in adult MAM rats suggested that central carbon metabolism disturbance and mitochondrial dysfunction were the potential mechanisms underlying the ReHo alterations. This study proposed frontal-posterior functional imbalance and aberrant function developmental patterns in SZ, suggesting that the adolescent visual cortex was a critical locus and a sensitive window in SZ development. These findings from linking data between hSZ and MAM rats may have a significant translational contribution to the development of effective therapies in SZ.

IntroductionShared decision-making (SDM) and trust building through continuity of care are known to play a pivotal role in improving appropriate antibiotic prescribing and use.ProblemHowever, less is known about how to effectively leverage these factors when present—or overcome them when not—to address community needs and improve patient liaison.MethodsWe addressed this question using a convergent parallel mixed-methods design. Focus group discussions (N = 13; August 2018–September 2020), were analyzed alongside a nationally-representative cross-sectional survey (N = 2004; November 2020–January 2021), in Singapore. Descriptive quantitative analyses and multivariable logistic regression were undertaken to examine antibiotic knowledge and factors associated with preference for SDM. Qualitative applied thematic analysis was integrated with these data to further explain the findings.FindingsPoor knowledge and misbeliefs on appropriate antibiotic use and antimicrobial resistance (AMR) were identified. For example, only 9% of the surveyed population understood that AMR occurs when the bacteria, not the human body, become resistant to antibiotics. Qualitative data corroborated the survey findings and suggested a shared value was placed on public education to avoid the fallout from resistant bacterial strains on current and future generations. This study also identified the opportunity to harness community trust in primary care doctors, who were described as highly valued educators for antibiotic use and AMR. Those who had trust in doctors were 75% more likely to prefer SDM (aOR 1.75, 95% CI 1.10–2.77, P = 0.017), especially adults aged ≥50 years who were receiving continued care with a regular doctor (aOR 1.83, 95% CI 1.18–2.86, P = 0.007). Continuity of care was observed to value-add SDM by building trusting relationships, though it was often absent in younger populations.ConclusionThis study highlights the long-term value-add of building on cultural capital pertaining to appropriate antibiotic use and AMR, by leveraging on the role of trust in doctors, desire for SDM and anchoring these in continuity of care when possible.RecommendationsUsing focused messaging and exploring alternative channels of communications such as annual check-ins or tele-consultations with a regular doctor, and emphasizing continuity of care across all age groups would help bridge the identified gaps.

It is difficult to form nanoparticles by traditional polymerization methods, using the azobenzene monomer with large hindrance. In this work, distillation precipitation polymerization (DPP) with lowering the monomer content at the beginning and distilling the solvent at a constant speed. Monofunctional 6-(4-methoxy-4′-oxygen-azobenzene) hexyl methacrylate (Azo) as a photo-responsive monomer and methacrylic acid (MAA) as a pH responsive monomer, were used to synthesize UCNPs@SiO2@PAzo/MAA nanoparticles. After the SiO2 was etched, UCNPs@PAzo/MAA nanocapsules (NCs) were formed. The trans isomer in the PAzo shell is converted into cis under 980 nm near-infrared (NIR) irradiation, leading to a variation of size and hydrophilicity of the nanocapsules. Controlled drug loading (∼17.5%) could be performed using UV irradiation, in which the pendant Azo groups have an cis “open” state and larger hydrophilicity. Under weak acid and NIR irradiation, the pendant Azo group with constant isomerization is like a “molecular impeller” agitator and the cumulative release rate of the doxorubicin (DOX) reaches 67.88%. Furthermore, UCNPs@PAzo/MAA nanocapsules were applied to the intracellular environment, and the cytotoxicity was studied. The cell images and cytotoxicity studies showed that the drug could be efficiently delivered to the nucleus by the UCNPs@PAzo/MAA nanocapsules in a controlled manner.

Ogura cytoplasmic male sterility (CMS) lines are widely used breeding materials in cruciferous crops and play important roles in heterosis utilization; however, the sterility mechanism remains unclear. To investigate the microspore development process and gene expression changes after the introduction of orf138 and Rfo, cytological observation and transcriptome analysis were performed using a maintainer line, an Ogura CMS line, and a restorer line. Semithin sections of microspores at different developmental stages showed that the degradation of tapetal cells began at the tetrad stage in the Ogura CMS line, while it occurred at the bicellular microspore stage to the tricellular microspore stage in the maintainer and restorer lines. Therefore, early degradation of tapetal cells may be the cause of pollen abortion. Transcriptome analysis results showed that a total of 1287 DEGs had consistent expression trends in the maintainer line and restorer line, but were significantly up- or down-regulated in the Ogura CMS line, indicating that they may be closely related to pollen abortion. Functional annotation showed that the 1287 core DEGs included a large number of genes related to pollen development, oxidative phosphorylation, carbohydrate, lipid, and protein metabolism. In addition, further verification elucidated that down-regulated expression of genes related to energy metabolism led to decreased ATP content and excessive ROS accumulation in the anthers of Ogura CMS. Based on these results, we propose a transcriptome-mediated induction and regulatory network for cabbage Ogura CMS. Our research provides new insights into the mechanism of pollen abortion and fertility restoration in Ogura CMS.

BackgroundSingapore’s national digital contact-tracing (DCT) tool—TraceTogether—attained an above 70% uptake by December 2020 after a slew of measures. Sentiment analysis can help policymakers to assess public sentiments on the implementation of new policy measures in a short time, but there is a paucity of sentiment analysis studies on the usage of DCT tools. ObjectiveWe sought to understand the public’s knowledge of, concerns with, and sentiments on the use of TraceTogether over time and their preferences for the type of TraceTogether tool. MethodsWe conducted a cross-sectional survey at a large public hospital in Singapore after the COVID-19 lockdown, from July 2020 through February 2021. In total, 4097 respondents aged 21-80 years were sampled proportionately by sex and 4 age groups. The open-ended responses were processed and analyzed using natural language processing tools. We manually corrected the language and logic errors and replaced phrases with words available in the syuzhet sentiment library without altering the original meaning of the phrases. The sentiment scores were computed by summing the scores of all the tokens (phrases split into smaller units) in the phrase. Stopwords (prepositions and connectors) were removed, followed by implementing the bag-of-words model to calculate the bigram and trigram occurrence in the data set. Demographic and time filters were applied to segment the responses. ResultsRespondents’ knowledge of and concerns with TraceTogether changed from a focus on contact tracing and Bluetooth activation in July-August 2020 to QR code scanning and location check-ins in January-February 2021. Younger males had the highest TraceTogether uptake (24/40, 60%), while older females had the lowest uptake (8/34, 24%) in the first half of July 2020. This trend was reversed in mid-October after the announcement on mandatory TraceTogether check-ins at public venues. Although their TraceTogether uptake increased over time, older females continued to have lower sentiment scores. The mean sentiment scores were the lowest in January 2021 when the media reported that data collected by TraceTogether were used for criminal investigations. Smartphone apps were initially preferred over tokens, but the preference for the type of TraceTogether tool equalized over time as tokens became accessible to the whole population. The sentiments on token-related comments became more positive as the preference for tokens increased. ConclusionsThe public’s knowledge of and concerns with the use of a mandatory DCT tool varied with the national regulations and public communications over time with the evolution of the COVID-19 pandemic. Effective communications tailored to subpopulations and greater transparency in data handling will help allay public concerns with data misuse and improve trust in the authorities. Having alternative forms of the DCT tool can increase the uptake of and positive sentiments on DCT.

Microbially enhanced coalbed methane (MECBM) has important theoretical and practical significance for reforming coal reservoir structure, alleviating greenhouse effects and energy crises and developing new sources of clean energy. In this study, No. 3 coal seams in Qinshui Basin were taken as research objects to analyze the pore structure characteristics after microbial treatment by means of low-temperature nitrogen adsorption (LTNA), mercury porosimetry (MP), and isothermal adsorption/desorption experiments. The results showed that after bioconversion, the specific surface area and pore volume increased from 1.79 m2/g and 0.0018 cm3/g to 4.01 m2/g and 0.0051 cm3/g respectively under liquid nitrogen testing; however, the specific surface area was reduced from 5.398 m2/g to 5.246 m2/g and the pore volume was increased from 0.053 cm3/g to 0.0626 cm3/g under MP. The fractal dimension based on the LTNA data indicated that the fractal dimension of micropores and minipores was increased from 2.73 to 2.60 to 2.89 and 2.81, however the fractal dimension of meso-macropores was decreased from 2.90 to 2.85. The volatile matter and fixed carbon were both reduced from 6.68% to 78.63%–5.09% to 75.63%, and the Langmuir volume and Langmuir pressure were increased from 34.84 cm3/g and 2.73 MPa to 36.34 cm3/g and 3.28 MPa, respectively. This result indicated that microorganism participated in the degradation of coal reservoir and promoted the production of methane gas, the meso-macropores were more obviously modified by microorganism, so that the pore diameter stabilized, the pores became smoother, the specific surface area decreased, and the pore volume increased. These are more beneficial to the adsorption and production of coalbed methane (CBM) after microbial treatment.

The mechanistic details of fatty acid uptake into cells remains poorly understood. Here, the authors identify CD36 internalization via cavaeolae and demonstrate dynamic palmitoylationof CD36 is required for endocytic uptake of fatty acids.

Background. The cholinergic anti-inflammatory pathway connects the immune response system and the nervous system via the vagus nerve. The key regulatory receptor is the α7-subtype of the nicotinic acetylcholine receptor (α7nAChR). Cholinergic anti-inflammatory pathway has been proved to be effective in suppressing the inflammation responses in acute lung injury (ALI). Dendritic cells (DCs), the important antigen-presenting cells, also express the α7nAChR. Past studies have indicated that reducing the quantity of mature conventional DCs and inhibiting the maturation of pulmonary DCs may prove effective for the treatment of ALI. However, the effects of cholinergic anti-inflammatory pathway on maturation, function, and quantity of DCs and conventional DCs in ALI remain unclear. Objective. It was hypothesized that cholinergic anti-inflammatory pathway may inhibit the inflammatory response of ALI by regulating maturation, phenotype, and quantity of DCs and conventional DCs. Methods. GTS-21 (GTS-21 dihydrochloride), an α7nAchR agonist, was prophylactically administered in sepsis-induced ALI mouse model and LPS-primed bone marrow-derived dendritic cells. The effects of GTS-21 were observed with respect to maturation, phenotype, and quantity of DCs, conventional DCs, and conventional DCs2 (type 2 conventional DCs) and the release of DC-related proinflammatory cytokines in vivo and in vitro. Results. The results of the present study revealed that GTS-21 treatment decreased the maturation of DCs and the production of DC-related proinflammatory cytokines in vitro and in sepsis-induced ALI mouse model; it reduced the quantity of CD11c+MHCII+ conventional DCs and CD11c+CD11b+ conventional DCs2 in vivo experiment. Conclusions. Cholinergic anti-inflammatory pathway contributes to the reduction in the inflammatory response in ALI by regulating maturation, phenotype, and quantity of DCs, conventional DCs, and conventional DCs2.

The aim of the current resting-state functional magnetic resonance imaging (fMRI) study was to investigate the potential mechanism of schizophrenia through the posterior–anterior cerebrum imbalance in methylazoxymethanol acetate (MAM) rats and to evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as an early-stage intervention. The rats were divided into four groups: the MAM-sham group, vehicle-sham group, MAM-rTMS group, and vehicle-rTMS group. The rTMS treatment was targeted in the visual cortex (VC) in adolescent rats. Granger Causality Analysis (GCA) was used to evaluate the effective connectivity between regions of interest. Results demonstrated a critical right VC–nucleus accumbens (Acb)–orbitofrontal cortex (OFC) pathway in MAM rats; significant differences of effective connectivity (EC) were found between MAM-sham and vehicle-sham groups (from Acb shell to OFC: t = −2.553, p = 0.021), MAM-rTMS and MAM-sham groups (from VC to Acb core: t = −2.206, p = 0.043; from Acb core to OFC: t = 4.861, p < 0.001; from Acb shell to OFC: t = 4.025, p = 0.001), and MAM-rTMS and vehicle-rTMS groups (from VC to Acb core: t = −2.482, p = 0.025; from VC to Acb shell: t = −2.872, p = 0.012; from Acb core to OFC: t = 4.066, p = 0.001; from Acb shell to OFC: t = 3.458, p = 0.004) in the right hemisphere. Results of the early-stage rTMS intervention revealed that right nucleus accumbens played the role as a central hub, and VC was a potentially novel rTMS target region during adolescent schizophrenia. Moreover, the EC of right nucleus accumbens shell and orbitofrontal cortex was demonstrated to be a potential biomarker. To our knowledge, this was the first resting-state fMRI study using GCA to assess the deficits of a visual-reward neural pathway and the effectiveness of rTMS treatment in MAM rats. More randomized controlled trials in both animal models and schizophrenia patients are needed to further elucidate the disease characteristics.

The antimicrobial susceptibility of 20 Lb. bulgaricus isolates from traditional fermented milk-originated was assessed and then determined the ability to transfer antibiotic resistance genes to other bacteria. The minimum inhibitory concentration of each strain was determined using a standardized dilution method. All the tested strains were found to be susceptible to gentamicin, erythromycin, clindamycin, neomycin, tetracycline, linezolid, chloramphenicol, rifampicin, and quinupristin/dalfopristin, while their susceptibilities to kanamycin, ciprofloxacin, streptomycin, trimethoprim, ampicillin, and vancomycin varied. Polymerase chain reaction (PCR) was used to check whether specific antibiotic resistance genes were present in these Lb. bulgaricus. We detected the rpoB, erm(B), aadA, bla, cat and vanX. Finally, a filter mating assay was applied to investigate the transferability of these resistance markers; and we observe no antibiotic resistance transfer between bacteria. This work demonstrates a low risk of lateral transfer of the antibiotic resistance gene of Lb. bulgaricus.

Background: Poor knowledge of antibiotic use drives poor antibiotic practices, but little is known about the influence of health information orientation (HIO) on knowledge of antibiotic use in the general public. Methods: We conducted a nationally-representative population-wide cross-sectional study (November 2020–January 2021), on a proportionately stratified random sample of 2004 Singapore residents aged ≥21 years. Multivariable logistic regression analysis was performed to assess the association between HIO and knowledge of antibiotic use. Results: Forty percent of respondents had low-levels of HIO (LL-HIO); they tended to be younger, not currently married, and did not have family/friends working in the healthcare sector. Respondents with LL-HIO (aOR 1.82, 95% CI 1.32–2.51, p < 0.001) were 82% more likely to have poor knowledge of antibiotic use. In particular, older adults aged ≥50 years with LL-HIO (aOR 1.81, 95% CI [1.32–2.51], p < 0.001) were much more likely to have poor knowledge than their HL-HIO counterparts. They were also less likely to use the Internet to seek health information and had poor eHealth efficacy. Conclusion: LL-HIO is independently associated with poor knowledge of antibiotic use. Educational strategies on antibiotic use should disseminate a consistent message through both online and offline platforms, involving traditional and non-traditional healthcare and non-healthcare influencers.

Abstract Background Resistance to thyroid hormone beta (RTHβ) results in symptoms of both increased and decreased thyroid hormone action. The effect of thyroid hormone changes in different types of autoimmune thyroid disease (AITD) in RTHβ is dynamic. Case presentation A 25-year-old Asian female had a RTHβ Y321C mutation with Hashimoto’s thyroiditis and type 2 diabetes mellitus. She was followed-up through gestation and two years postpartum, revealing development of postpartum thyroiditis (PPT) with characteristic wide fluctuations in serum thyrotropin levels, and of spontaneous recovery from an episode of transient hypothyroidism. The presence of RTHβ did not prolong thyroiditis duration nor progressed toward permanent hypothyroidism. Prenatal genetic analysis was not performed on the unaffected fetus, and did not result in congenital hypothyroidism, possibly because maternal free thyroxine (FT4) levels were mildly elevated at less than 50% above the reference range in early gestation and gradually decreased to less than 20% after the 28th gestational week. Conclusion In RTHβ patients with autoimmune thyroid disease, episodes of thyroid dysfunction can significantly alter thyrotropin levels. During pregnancy, mildly elevated maternal free thyroxine levels less than 20% above the upper limit may not be harmful to unaffected fetuses. Unnecessary thyroid hormone control and fetal genetic testing was avoided during the gestational period with monthly follow-up.

Objective: Suicide is the leading cause of death from bipolar disorder (BD). At least 25–50% of the patients with BD will attempt suicide, with suicide rates much higher in women patients than in men. It is crucial to explore the potential neural mechanism underlying suicidality in women with BD, which will lead to understanding and detection of suicidality and prevent death and injury from suicide.Methods: Brain function and structure were measured by amplitude of low-frequency fluctuation (ALFF) and gray matter volume (GMV) in 155 women [30 women with BD and a history of suicidality, 50 women with BD without suicidality, and 75 healthy controls (HC)]. The differences in ALFF and GMV across the BD with suicidality, BD without suicidality, and HC groups were investigated.Results: BD with suicidality showed significantly increased ALFF in the left and right cuneus compared with BD without suicidality and HC groups. Moreover, the GMV in the left lateral prefrontal cortex and left cuneus in BD with suicidality were significantly lower than those in BD without suicidality and HC groups, while the GMV of the right ventral prefrontal cortex was significantly decreased in both BD with and without suicidality groups.Conclusions: This study, combining functional and structural neuroimaging techniques, may help to identify specific pathophysiological changes in women with BD and suicidality. Increased ALFF and less GMV in cuneus might represent the neuroimaging features of suicidality in women with BD. Investigating this potential neuromarker for suicidality in women with BD may lead to the ability to prevent suicidality.

Growing concerns about urban runoff pollution and water scarcity caused by urbanization have prompted the application of bioretention facilities to manage urban stormwater. The purpose of this study was to evaluate the performance of proposed bioretention facilities regarding road runoff pollutant removal and the variation characteristics of the media physicochemical properties and microbial diversity in dry-cold regions. Two types of bioretention facilities were designed and then constructed in Tianjin Eco-city, China, on the basis of combined soil filter media screened by a laboratory-scale test with a modified bioretention facility (MBF) containing soil moisture conservation ropes. Redundancy analysis was performed to evaluate the relationships between the variation in media physicochemical properties and microbial communities. An increase in media moisture could promote an increase in the relative abundance of several dominant microbial communities. In the MBF, the relatively low nitrate-nitrogen (NO3-N) (0.75 mg/L) and total nitrogen (TN) (4.71 mg/L) effluent concentrations, as well as better removal efficiencies for TN and NO3-N in challenge tests, were mainly attributed to the greater relative abundance of Proteobacteria (25.2%) that are involved in the microbial nitrogen transformation process. The MBF also had greater media microbial richness (5253 operational taxonomic units) compared to the conventional bioretention facility and in situ saline soils. The results indicate that stormwater runoff treated by both bioretention facilities has potential use for daily greening and road spraying. The proposed design approach for bioretention facilities is applicable to LID practices and sustainable stormwater management in other urban regions.

Abstract To study the fractal dimensions of the soil particle size distributions (PSDs) within different plantations (of Pinus densiflora, Quercus acutissima, Robinia pseudoacacia, and Larix kaempferi) and evaluate PSDs as an indicator of the likelihood of Robinia pseudoacacia invasion, the soil porosity of 0–20 cm soil layers was measured at different plantations in the Yaoxiang Forest Farm, Shandong Province, China. The results showed that the fractal dimension (D m) values varied from 2.59 to 2.70 among the different plantations and were significantly negatively correlated to sand content and positively correlated to silt content and clay content. Significant negative correlations were observed between D m and both soil organic matter (SOM) (P

Objectives: Understanding factors influencing inappropriate antibiotic use can guide the design of interventions to improve antibiotic practices and reduce antimicrobial resistance (AMR). Methods: A nationally representative cross-sectional survey (N = 2004) was conducted between November 2020 and January 2021. Knowledge of antibiotic use and AMR using the World Health Organization’s Multi-Country AMR Survey questionnaire, and antibiotic practices were examined. Multivariable logistic regression was performed to identify factors associated with inappropriate antibiotic use and examine effect measure modifications. Results: After adjusting for potential confounding, poor knowledge of antibiotic use was associated with a 3x increased odds of inappropriate antibiotic use in adults aged ≥50 years (aOR 3.11, 95% CI [2.24–4.32]), 5× increased odds in those aged 35–49 years (aOR 4.88, 95% CI [3.32–7.16]), and 7× increased odds in those aged 21–34 years (aOR 6.58, 95% CI [4.19–10.33]). While there was no statistically significant association in adults aged ≥50 years, poor knowledge of AMR increased the odds of inappropriate antibiotic use by 4 times in adults aged 35–49 years (aOR 3.73, 95% CI [1.53–9.11]) and 5 times in those aged 21–34 years (aOR 4.90, 95% CI [1.84–13.02]). Conclusions: Targeted educational interventions for specific age groups are needed in conjunction with empowering the public with knowledge of antibiotic use and AMR.

Antimicrobial stewardship programmes (ASPs) in hospitals are predominantly led by specific ASP physicians and pharmacists. Limited studies have been conducted to appreciate non-ASP-trained hospital pharmacists’ perspectives on their roles in antimicrobial stewardship. Focus group discussions (FGDs) were conducted with 74 pharmacists, purposively sampled from the 3 largest acute-care public hospitals in Singapore, to explore facilitators and barriers faced by them in antimicrobial stewardship. Applied thematic analysis was conducted and codes were categorised using the social–ecological model (SEM). At the intrapersonal level, pharmacists identified themselves as reviewers for drug safety before dispensing, confining to a restricted advisory role due to lack of clinical knowledge, experience, and empowerment to contribute actively to physicians’ prescribing decisions. At the interpersonal level, pharmacists expressed difficulties conveying their opinions and recommendations on antibiotic therapy to physicians despite frequent communications, but they assumed critical roles as educators for patients and their caregivers on proper antibiotic use. At the organisational level, in-house antibiotic guidelines supported pharmacists’ antibiotic interventions and recommendations. At the community level, pharmacists were motivated to improve low public awareness and knowledge on antibiotic use and antimicrobial resistance. These findings provide important insights into the gaps to be addressed in order to harness the untapped potential of hospital pharmacists and fully engage them in antimicrobial stewardship.

Stormwater runoff management is challenging in a highly urbanised tropical environment due to the unique space constraints and tropical climate conditions. A modular bioretention tree (MBT) with a small footprint and a reduced on-site installation time was explored for application in a tropical environment. Tree species used in the pilot studies were Talipariti tiliaceum (TT1) and Sterculia macrophylla (TT2). Both of the MBTs could effectively remove total suspended solids (TSS), total phosphorus (TP), zinc, copper, cadmium, and lead with removal efficiencies of greater than 90%. Total nitrogen (TN) removal was noted to be significantly higher in the wet period compared to the dry period (p < 0.05). Variation in TN removal between TT1 and TT2 were attributed to the nitrogen uptake and the root formation of the trees species. A field study MBT using Talipariti tiliaceum had a very clean effluent quality, with average TSS, TP, and TN effluent EMC of 4.8 mg/L, 0.04 mg/L, and 0.27 mg/L, respectively. Key environmental factors were also investigated to study their impact on the performance of BMT. It was found that the initial pollutant concentration, the dissolved fraction of influent pollutants, and soil moisture affect the performance of the MBT. Based on the results from this study, the MBT demonstrates good capability in the improvement of stormwater runoff quality.

Abstract Background The extensive use of antibiotics in medicine has raised serious concerns about biosafety. However, the effect of antibiotic application on the adaptive evolution of microorganisms, especially to probiotic bacteria, has not been well characterized. Thus, the objective of the current work was to investigate how antibiotic selection forces might drive genome adaptation using Lactobacillus (L.) casei Zhang as a model. Methods Two antibiotics, amoxicillin and gentamicin, were consistently applied to the laboratory culture of L. casei Zhang. We then monitored the mutations in the bacterial genome and changes in the minimum inhibitory concentrations (MICs) of these two antibiotics along a 2000-generation-cultivation lasted over 10 months. Results We found an approximately 4-fold increase in the genome mutation frequency of L. casei Zhang, i.e. 3.5 × 10-9 per base pair per generation under either amoxicillin or gentamicin stress, when compared with the parallel controls grown without application of any antibiotics. The increase in mutation frequency is significantly lower than that previously reported in Escherichia (E.) coli. The rate of de novo mutations, i.e. 20 per genome, remained low and stable throughout the long-term cultivation. Moreover, the accumulation of new mutations stopped shortly after the maximum bacterial fitness (i.e. the antibiotic MICs) was reached. Conclusions Our study has shown that the probiotic species, L. casei Zhang, has high genome stability even in the presence of long-term antibiotic stresses. However, whether this is a species-specific or universal characteristic for all probiotic bacteria remains to be explored.

Amoxicillin is one of the most commonly prescribed antibiotics for bacterial infections and gastrointestinal disorders. To investigate the adaptation of Lactobacillus (L.) casei Zhang to amoxicillin stress, an iTRAQ-based comparative proteomic analysis was performed to compare the protein profiles between the parental L. casei Zhang and its amoxicillin-resistant descendent strains. Our results revealed a significant increase in the relative expression of 38 proteins (>2.0-folds, P < 0.05), while the relative expression of 34 proteins significantly decreased (

Lactobacillus (L. casei) Zhang is a koumiss-originated probiotic strain, which was used as a model in a long-term antibiotics-driven evolution experiment to reveal bacterial evolutionary dynamics; and we isolated gentamycin-resistant L. casei Zhang descendents. To decipher the gentamycin resistance mechanism, here we cultivated the parental L. casei Zhang and its descendent cells in an antibiotics-containing environment to compare their global protein expression profiles using the iTRAQ-based proteomic approach. A total of 72 proteins were significantly up-regulated (>2.0-fold, P < 0.05), whilst 32 proteins were significantly down-regulated

Aluminum-based water treatment residue (Al-WTR) generated during the drinking water treatment process is a readily available recycled material with high phosphorus (P) adsorption capacity. The P adsorption capacity of Al-WTR generated from Singapore’s water treatment plant was evaluated with reference to particle size range, adsorption pH and temperature. Column tests, with WTR amendments in sand with and without compost, were used to simulate the bioretention systems. The adsorption rate decreased with increasing WTR sizes. Highest P adsorption capacity, 15.57 mg PO43−-P/g WTR, was achieved using fine WTR particles (>50% particles at less than 0.30 mm). At pH 4, the contact time required to reduce effluent P concentration to below the detectable range was half compared with pH 7 and 9. The adsorption rate observed at 40 ± 2 °C was 21% higher compared with that at 30 ± 2 °C. Soil mixes amended with 10% WTR and compost were able to maintain consistently high (90%) total phosphorus (TP) removal efficiency at a TP load up to 6.45 g/m3. In contrast, TP removal efficiencies associated with columns without WTR amendment decreased to less than 45% as the TP load increased beyond 4.5 g/m3. The results showed that WTR application is beneficial for enhanced TP removal in bioretention systems.

The composition of body fluids has become one of the most commonly used methods for diagnosing various diseases or monitoring the drug responses, especially in serum/plasma. It is therefore vital for investigators to find an appropriate way to collect blood samples from laboratory animals. This study compared blood samples collected from different sites using the NMR based metabolomics approach. Blood samples were collected from the saphenous vein (awake state), tail vein (awake and anesthetized states after administration of sevoflurane or pentobarbital) and the inferior thoracic vena cava (ITVC, anesthetized state). These approaches from the saphenous and tail veins have the potential to enable the collection of multiple samples, and the approach from ITVC is the best method for the collection of blood for the terminate state. The compositions of small molecules in the serum were determined using the 1H-NMR method, and the data were analyzed with traditional correlation analysis, principle component analysis (PCA) and OPLS-DA methods. The results showed that acute anesthesia significantly influenced the composition of serum in a very short period, such as the significant increase in glucose, and decrease in lactate. This indicates that it is better to obtain blood samples under the awake state. From the perspective of animal welfare and multiple sampling, the current study shows that the saphenous vein and tail vein are the best locations to collect multiple blood samples for a reduced risk of injury in the awake state. Furthermore, it is also suitable for investigating pharmacokinetics and the effects of drug intervention on animals.

Background and objective Whether gemcitabine plus platinum chemotherapy is superior to gemcitabine or platinum single-agent chemotherapy for patients with non-small cell lung cancer (NSCLC) is still in dispute, and the aim of this study is to evaluate the efficacy and safety of gemcitabine combining platinum chemotherapy for patients with NSCLC. Methods We searched relevant randomized controlled trials (RCTs) from VIP, CBM, CNKI, the Cochrane library, PUBMED and EMBASE. We traced the related references and experts in this field and communicated with other authors to obtain the information that has not been found. We made quality assessment of qualified RCTs assessed by the exclusion and inclusion criteria and used RevMan 5.0 provided by the Cochrane Collaboration to perform meta-analysis. Results Four RCTs were eligible and included 984 patients. Meta analysis results suggested that: compared with gecitabine single-agent chemotherapy, the combination had a statistically significant benefit in increasing the response rate (OR=3.29, 95%CI: 1.79-6.05, P=0.000 1) and 2-year survival rate (OR=3.22, 95%CI: 1.45-7.12, P=0.004) while increased the risk of the incidence of adverse reactions, especially the grade 3-4 thrombocytopenia (RR=8.16, 95%CI: 1.71-39.07, P=0.009); compared with cisplatin single-agent chemotherapy, the combination had a statistically significant benefit in increasing the response rate (OR=3.51, 95%CI: 2.20-5.60, P

Background and objective It was unclear whether advanced non-small cell lung cancer (NSCLC) patients could benefit from erlotinib therapy. This study was aimed to evaluate the efficacy and safety of NSCLC patients treated with erlotinib. Methods The relevant randomized controlled trials (RCT) were searched from VIP, CMB, CNKI, PubMed, EMBASE and The Cochrane Library. The related references and experts in this field were traced, and other authors were communicated with to obtain the information that has not been found. Quality assessment of qualified RCTs assessed by the exclusion and inclusion criteria and RevMan 5.0 provided by the Cochrane Collaboration was used to perform meta-analysis. Results Three RCTs involving 2 969 patients were included. Meta analysis results suggested that erlotinib was superior to placebo for one year survival rate (OR=1.18, 95%CI: 1.01-1.38), tumor response rate (OR=1.24, 95%CI: 1.03-1.49), median overall survival, median progression-free survival and tumor responses duration. At the same time, the incidence of grade 3-4 skin rash (OR=16.33, 95%CI: 7.01-38.02) and diarrhea (OR=5.02, 95%CI: 2.93-8.60) of the adverse reactions was increased. Conclusion Advanced non-small cell lung cancer patients could benefit from Erlotinib therapy, but the incidence of skin rash and diarrhea was significantly increased, and in the absence of damage to the blood system, serious liver and kidney damage, cardiac toxicity, etc, there were no difference with placebo.