The application of large language models in medicine: A scoping review.

This study systematically reviewed the application of large language models (LLMs) in medicine, analyzing 550 selected studies from a vast literature search. LLMs like ChatGPT transformed healthcare by enhancing diagnostics, medical writing, education, and project management. They assisted in drafting medical documents, creating training simulations, and streamlining research processes. Despite their growing utility in assisted diagnosis and improving doctor-patient communication, challenges persisted, including limitations in contextual understanding and the risk of over-reliance. The surge in LLM-related research indicated a focus on medical writing, diagnostics, and patient communication, but highlighted the need for careful integration, considering validation, ethical concerns, and the balance with traditional medical practice. Future research directions suggested a focus on multimodal LLMs, deeper algorithmic understanding, and ensuring responsible, effective use in healthcare.

An ATPase-Mimicking MXene nanozyme pharmacologically breaks the ironclad defense system for ferroptosis cancer therapy.

Anticancer nanomedicines used for ferroptosis therapy generally rely on the direct delivery of Fenton catalysts to drive lipid peroxidation in cancer cells. However, the therapeutic efficacy is limited by the ferroptosis resistance caused by the intracellular anti-ferroptotic signals. Herein, we report the intrinsic ATPase-mimicking activity of a vanadium carbide MXene nanozyme (PVCMs) to pharmacologically modulate the nuclear factor erythroid 2-related factor 2 (Nrf2) program, which is the master anti-ferroptotic mediator in the ironclad defense system in triple-negative breast cancer (TNBC) cells. The PVCMs perform high ATPase-like activity that can effectively and selectively catalyze the dephosphorylation of ATP to generate ADP. Through a cascade mechanism initiated by falling energy status, PVCMs can powerfully hinder the Nrf2 program to selectively drive ferroptosis in TNBC cells in response to PVCMs-induced glutathione depletion. This study provides a paradigm for the use of pharmacologically active nanozymes to moderate specific cellular signals and elicit desirable pharmacological activities for therapeutic applications.

The causal effect of mTORC1-dependent circulating protein levels on nonalcoholic fatty liver disease: A Mendelian randomization study.

BACKGROUND: The mechanistic target of rapamycin (mTOR) signal pathway plays a crucial role in the development of nonalcoholic fatty liver disease (NAFLD). However, the causal effect of mTOR downstream proteins on NAFLD remains unknown. AIMS: We conducted a two-sample Mendelian randomization (MR) study to investigate whether the mTOR-dependent circulating proteins, including Eukaryotic Initiation Factor 4E Binding Proteins (eIF4EBPs), Ribosomal Protein S6K kinase 1 (RP-S6K), Eukaryotic Initiation Factor 4E (eIF4E), Eukaryotic Initiation Factor 4A (eIF4A) and Eukaryotic Initiation Factor 4 G (eIF4G), have causal effects on the risk of NAFLD. METHODS: The causal estimate was evaluated with the inverse-variance weighted (IVW) method in discovery stage and validation stage. The single-nucleotide polymorphisms (SNPs) were selected to genetically predict exposures from Genome-Wide Association Studies (GWAS). Exposures with statistically significant effects in the discovery dataset would be further validated in the validation dataset. RESULTS: MR study revealed that eIF4E had a causal effect on NAFLD in both discovery stage (OR = 1.339, P = 0.037) and validation stage (OR = 1.0007, P = 0.022). Sensitivity analyses confirmed robustness of the results. CONCLUSION: The genetically predicted higher level of mTOR-dependent eIF4E in plasma might have a causal effect on the occurrence of NAFLD.

Effect of a Self-Assembled Nucleating Agent on the Crystallization Behavior and Spherulitic Morphology of Poly(lactic acid).

Herein, decanedioic acid dibenzoylhydrazide (DDBH) was used as a nucleating agent to improve the crystallization of poly(lactic acid) (PLA). The formation of DDBH assemblies in PLA melts at different concentrations was systematically investigated. The DDBH (0.5-0.9 wt %) recrystallized as dendrite-like structures during the isothermal crystallization process, and the crystal morphology of PLA underwent a morphological change from spherical form to a similar dendritic crystal form. Differential scanning calorimetry and in situ wide-angle X-ray diffraction analysis results showed that crystallizability and overall crystallization rate of PLA were enhanced by the addition of DDBH. The half-crystallization time at 120 °C reduced to 0.28 min compared to pure PLA (6.12 min), after adding 0.9 wt % DDBH. Moreover, the crystallinity and lamellar thickness of crystalline PLA increased, while the size of the microcrystal of PLA decreased with an increase in DDBH content. The heat deflection temperatures of PLA/DDBH blends increased and hence heat resistance improved.

Inhibition of LNC EBLN3P Enhances Radiation-Induced Mitochondrial Damage in Lung Cancer Cells by Targeting the Keap1/Nrf2/HO-1 Axis.

Lung cancer remains the leading cause of cancer-related deaths in both women and men, claiming millions of lives worldwide. Radiotherapy is an effective modality for treating early-stage lung cancer; however, it cannot completely eradicate certain tumor cells due to their radioresistance. Radioresistance is commonly observed in conventionally fractionated radiotherapy, which can lead to treatment failure, metastasis, cancer recurrence, and poor prognosis for cancer patients. Identifying the underlying molecular mechanisms of radioresistance in lung cancer can promote the development of effective radiosensitizers, thereby improving patients' life expectancy and curability. In this study, we identified LNC EBLN3P as a regulator of lung cancer cell proliferation and radiosensitivity. The repression of LNC EBLN3P could increase ROS production and mitochondrial injury in NSCLC cells. In addition, knocking down LNC EBLN3P increased the binding of Nrf2 to Keap1, resulting in enhanced Nrf2 degradation, decreased translocation of Nrf2 to the nucleus, reduced expression of antioxidant protein HO-1, weakened cellular antioxidant capacity, and increased radiosensitivity of NSCLC cells. These findings suggest that targeting LNC EBLN3P could be a promising strategy for developing novel radiosensitizers in the context of conventional radiotherapy for NSCLC.

Fabrication high toughness poly(butylene adipate-co-terephthalate)/thermoplastic starch composites via melt compounding with ethylene-methyl acrylate-glycidyl methacrylate.

The preparation of biodegradable composites with high toughness and low cost is of great significance for their application and promotion in the packaging field. As a renewable and biodegradable material with abundant sources, the inclusion of starch in biodegradable composites can significantly reduce costs. However, the poor compatibility between starch and matrix severely limits its large-scale practical application. In this work, the poly(butylene adipate-co-terephthalate)/thermoplastic starch/ethylene-methyl acrylate-glycidyl methacrylate (PBAT/TPS/EGMA) blends with high toughness were prepared by melt compounding. The elongation at break increased significantly from 533 ± 125 % for the PBAT/TPS(60/40) blend to 1188 ± 28 % for the PBAT/TPS/EGMA(60/40/2) blend. According to the analysis of Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscope (SEM), the toughness improvement brought about by the addition of EGMA can be attributed to the enhanced compatibility between PBAT and TPS and the refinement of TPS particle size. The knowledge obtained from this study provides a method to enhance the toughness of biodegradable polymer composites with high TPS loading, which will facilitate the practical application of starch in the packing field.

Discovery of Novel Potent Covalent Glutathione Peroxidase 4 Inhibitors as Highly Selective Ferroptosis Inducers for the Treatment of Triple-Negative Breast Cancer.

Glutathione peroxidase 4 (GPX4) is a promising target to induce ferroptosis for the treatment of triple-negative breast cancer (TNBC). We designed and synthesized a novel series of covalent GPX4 inhibitors based on RSL3 and ML162 by structural integration and simplification strategies. Among them, compound C18 revealed a remarkable inhibitory activity against TNBC cells and significantly inhibited the activity of GPX4 compared to RSL3 and ML162. Moreover, it was identified that C18 could notably induce ferroptosis with high selectivity by increasing the accumulation of lipid peroxides (LPOs) in cells. Further study demonstrated that C18 covalently bound to the Sec46 of GPX4. Surprisingly, C18 exhibited an outstanding potency of tumor growth inhibition in the MDA-MB-231 xenograft model with a TGI value of 81.0%@20 mg/kg without obvious toxicity. Overall, C18 could be a promising GPX4 covalent inhibitor to induce ferroptosis for the treatment of TNBC.

Small Molecules Mediated the Chirality Transfer in Self-Assembled Nanocomposites with Strong Circularly Polarized Luminescence.

Manipulation of the chirality at all scales has a cross-disciplinary importance and may address key challenges at the heart of physical sciences. One critical question in this field is how the chirality of one entity can be transferred to the asymmetry of another entity. Here, we find that small molecules play a crucial role in the chirality transfer from chiral organic molecules to CdSe/CdS nanorods, where the handedness of the nanorod assemblies either agrees or disagrees with that of the molecular assemblies, leading to the positive or inverse chirality transfer. The assembling mode of nanorods on the molecular assemblies, where the nanorods are either lying or standing, is closely associated with the handedness of the nanorod assemblies, resulting in opposite chirality. Furthermore, we have found that circularly polarized emission from chiral assemblies of nanorods is dependent on molecular additives. The promoted luminescence dissymmetry factor (glum) of the nanocomposites with a high value of ∼0.3 could be attained under optimal conditions.

Effect of e-health interventions on HIV prevention: a protocol of systematic review and meta-analysis.

BACKGROUND: Global epidemiological data indicates that despite implementation of multiple interventions and significant financial investment, the HIV/AIDS epidemic remained inadequately controlled as of 2020. E-health presents a novel approach in delivering health information and health care and has gained popularity in HIV prevention worldwide. However, evidence on the effectiveness of e-health interventions on HIV prevention among diverse populations remains inadequate. Our study aims to systematically evaluate the effectiveness of varying e-health interventions on HIV prevention, with the objective of providing data support and guidance for the development of future e-health HIV intervention strategies. METHODS: A systematic search of electronic English databases, including MEDLINE through PubMed, Embase, Scopus, and Web of Science, along with three Chinese databases, including National Knowledge Infrastructure (CNKI), Chinese Wanfang Digital Periodicals (WANFANG), and Chinese Science and Technology Periodicals (VIP) database, will be conducted for the period of 1 January 1980 to 31 December 2022. Additionally, gray literature and unpublished trials in trial registers will be searched. Studies aimed at HIV prevention through e-health interventions, with full-text publications available in either English or Chinese, will be included. Study types will be limited to RCT, cluster RCT, and quasi-experiment study. The risk of bias in individual studies will be assessed following the guideline highlighted by the Cochrane Handbook for Systematic Reviews of Interventions. The outcomes will cover cognitive, behavioral, psychological, management, and biological measures of individuals involved in e-health interventions. The quality of evidence will be assessed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Ultimately, a systematic review with meta-analysis will be conducted to compare the effectiveness of e-health interventions among diverse populations. DISCUSSION: This systematic review seeks to establish novel insights into the effectiveness of e-health interventions in diverse populations worldwide. It will inform the design and use of e-health interventions to optimize HIV-related strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022295909.

Short-term outcomes of perioperative glucocorticoid administration in patients undergoing liver surgery: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: The purpose of this systematic review and meta-analysis was to investigate whether glucocorticoid might be beneficial after hepatectomy. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Cochrane Library and Web of Science. ELIGIBILITY CRITERIA: We included studies assessing the efficacy of perioperative glucocorticoid administration in patients undergoing liver surgery. DATA EXTRACTION AND SYNTHESIS: Four data bases were retrieved for all randomised controlled trials. We considered postoperative complications, hospital stay and postoperative chemistry evaluations as outcomes. Pooled effects of dichotomic variables were expressed as relative risk (RR) with a 95% CI. The mean difference was used for continuous variables and an inverse variance statistical method was adopted. RESULTS: Fourteen studies with 1205 patients were included. Lower risk of overall complications was associated with glucocorticoid (RR, 0.77; 95% CI 0.64 to 0.92), while no difference was found in hospital stay (RR, 0.02; 95% CI -0.47 to 0.51). There were also improvements in postoperative chemistry evaluations including interleukin 6 on day 1 and 3, C reactive protein on day 1, 2 and 3, international normalised ratio on day 2, total bilirubin on day 1, 2, 3 and 5, albumin on day 1. CONCLUSION: Current evidence indicated that perioperative glucocorticoid administration for patients undergoing hepatectomy reduced the risk of overall complications with inhibited postoperative inflammatory response and improved postoperative liver function. PROSPERO REGISTRATION NUMBER: CRD42022307533.

Adjuvant chemoradiotherapy in resected gallbladder cancer: A SEER-based study.

Background: The prognosis of gallbladder cancer (GBC) is dismal. This study aimed to compare the outcomes of adjuvant chemoradiotherapy (ACR) with those of surgery alone (S) and adjuvant chemotherapy (AC). Method: The Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify patients diagnosed with GBC and undergoing surgery between 2004 and 2015. The patients were divided into the S, AC, and ACR groups according to their treatment. Categorical variables were compared by Pearson's chi-square test, and a 1:1:1 propensity score matching analysis (PSM) was performed. Overall survival was assessed by Kaplan-Meier curves with log-rank tests. Subgroup analyses were conducted. Result: A total of 5451 patients were identified in the SEER database. After PSM, the two-year survival among patients who received S, AC, and ACR was 36%, 39%, and 45%, respectively. ACR was associated with improved two-year survival (p < 0.001), while the survival rates were similar in the AC and S groups (p = 0.127) but better in the ACR group than in the AC group (p = 0.012). Subgroup analyses indicated that while the two-year survival rates did not differ significantly in stage II GBC patients between the groups (all p > 0.05), ACR was associated with significantly improved two-year survival in stage Ⅲa (p = 0.008), Ⅲb (p < 0.001), and Ⅳb (p < 0.001) GBC patients. Conclusion: The combination of surgery and ACR as the treatment modality provided greater survival benefits for GBC patients, particularly for those with advanced tumor staging.

Spatial and temporal distribution of emerging airborne viral infectious diseases outbreaks on a global scale.

Aim: This study aimed to explore the spatial and temporal characteristics of emerging airborne viral infectious diseases outbreaks worldwide. Subject and methods: We conducted a systematic literature review on outbreaks of emerging airborne viral infectious diseases and calculated outbreak number and intensity at the country level. Fisher's exact test was used to compare the viral infectious diseases outbreaks in different income-level regions. To identify the major airborne viral infectious diseases outbreaks, we ranked and extracted the leading viral infectious diseases in outbreak number and intensity in each country by year. Results: A total of 2505 outbreaks were reported from 1873 to 2021 across 2010 studies. There were 47 countries (47/130, 36.15%) with more frequent emerging airborne viral infectious disease outbreaks (more than nine outbreaks), and these countries mainly distributed in high-income regions (22/47 countries, 46.81%, p < 0.05), especially in Western Europe (14/47 countries, 29.79%, p < 0.05). The number of overall outbreaks was more in the United States and China than in other countries in different years. Outbreaks of measles and influenza are always frequent and intense. Highly pathogenic human coronaviruses infection caused short-term pandemics during which their outbreak number and intensity exceeded other viruses. Rift valley fever outbreaks in the human population are spreading outside of Africa through the flow of goods and travelers. Conclusion: Countries in high-income regions reported more emerging airborne viral infectious diseases outbreaks, especially in the Western European region, the United States, and China. It is urgent to strengthen collaborative surveillance of emerging airborne viruses, cross-border flow of goods and travelers, and ecological environment to avoid the spread of viral infectious diseases outbreaks worldwide. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01850-3.

A multicomponent gas wavelength selection method based on an absorbance mathematical model.

In order to quickly and accurately determine the optimal absorption spectra of the gases to be measured, a method for selecting the optimal wavelengths for multicomponent gases was proposed. A mathematical model of the absorbance of multicomponent gases was established, and the selection conditions of the optimal wavelengths were analyzed from the perspective of geometric significance. The best measurement spectra for the gas mixture of CO2, CH4, and C2H2 were determined and the gas mixture was measured using the supercontinuum laser absorption spectroscopy (SCLAS) technique, and the partial least squares (PLS) model and the least squares (LS) model were established to quantify the experimental results. The results showed that the PLS model had better prediction performance. The root mean square error (RMSE) of the calibration set PLS model for CO2 and CH4 was 0.1652 and 0.0053, the RMSE of the prediction set PLS model was 0.1991 and 0.0163, and the determination coefficient (R2) of the models was above 0.9. The experimental results show that the optimal wavelength selection method for multicomponent gases proposed in this study can effectively determine the optimal measurement spectral lines for the gases to be measured.

Comparison of the Users' Attitudes Toward Cannabidiol on Social Media Platforms: Topic Modeling Study.

BACKGROUND: As one of the major constituents of the cannabis sativa plant, cannabidiol (CBD) is approved for use in medical treatment and cosmetics because of its potential health benefits. With the rapid growth of the CBD market, customers purchase these products, and relevant discussions are becoming more active on social media. OBJECTIVE: In this study, we aimed to understand the users' attitudes toward CBD products in various countries by conducting text mining on social media in countries with different substance management policies. METHODS: We collected posts from Reddit and Xiaohongshu, conducted topic mining using the latent Dirichlet allocation model, and analyzed the characteristics of topics on different social media. Subsequently, a co-occurrence network of high-frequency keywords was constructed to explore potential relationships among topics. Moreover, we conducted sentiment analysis on the posts' comments and compared users' attitudes toward CBD products on Reddit and Xiaohongshu using chi-square test. RESULTS: CBD-related posts on social media have been rapidly increasing, especially on Xiaohongshu since 2019. A total of 1790 posts from Reddit and 1951 posts from Xiaohongshu were included in the final analysis. The posts on the 2 social media platforms, Reddit and Xiaohongshu, were categorized into 7 and 8 topics, respectively, by the latent Dirichlet allocation model, and these topics on the 2 social media were grouped into 5 themes. Our study showed that the themes on Reddit were mainly related to the therapeutic effects of CBD, whereas the themes on Xiaohongshu concentrated on cosmetics, such as facial masks. Theme 2 (CBD market information) and theme 3 (attitudes toward CBD) on Reddit had more connections with other themes in the co-occurrence network, and theme 3 and theme 1 (CBD therapeutic effects) had a high co-occurrence frequency (22,803/73,865, 30.87%). Meanwhile, theme 1 (CBD cosmetics) on Xiaohongshu had various connections with others (169,961/384,575, 44.19%), and the co-occurrence frequency of theme 4 (CBD ingredients) and theme 1 was relatively prominent (27,128/49,312, 55.01%). Overall, users' comments tended to be positive for CBD-related information on both Reddit and Xiaohongshu, but the percentage was higher on Xiaohongshu (82.25% vs 86.18%; P<.001), especially in cosmetics and medical health care products. CONCLUSIONS: The CBD market has grown rapidly, and the topics related to CBD on social media have become active. There are apparent differences in users' attitudes toward CBD in countries with different substance management policies. Targeted CBD management measures should be formulated to suit the prevalence of CBD use of each country.

Understanding the different effects of 4d-transition metals on the performance of Li-rich cathode Li2MnO3 by first-principles.

The poor cycling performance of Li-rich cathode Li2MnO3, a promising cathode for next-generation Li-ion batteries, limits its commercial applications. Transition metal (TM) doping is widely applied to optimize the electrochemical performance of Li2MnO3, where the d valence electrons of the TM play a crucial role. Nevertheless, the rule of the doping effect of TM with various numbers of d electrons has not been well summarized. In this work, 4d-TMs (Zr, Nb, Mo, Ru and Rh) are selected as dilute doping elements for Li2MnO3 to evaluate their effect on the performance of Li2MnO3 through first-principles calculations. The calculations indicate that as the number of 4d electrons increases, the doped TM transforms from an electrochemically inert state (Zr and Nb) to an electrochemically active state (Mo, Ru and Rh) in Li2MnO3. Meanwhile, the orbital hybridization between the 4d electrons of the TM and the 2p electrons of O becomes stronger from Zr to Rh, which promotes the co-oxidation of the TM and O for charge compensation and alleviates the excessive oxidation of O, thus enhancing the stability of O. Moreover, the oxidation of the doped TM and lattice Mn during charging can trigger a decrease in the initial average delithiation potential. Although the 4d-TMs exhibit slight promoting or inhibiting effects on Li diffusion, no obvious rule related to the number of d electrons has been found. Our work highlights the rule of the doping effect of TMs with different 4d electrons on the electrochemical performance of Li2MnO3 and would facilitate a better design of Li2MnO3 cathode materials.

Extrapulmonary tuberculosis in China: a national survey.

OBJECTIVES: Extrapulmonary tuberculosis (EPTB) is not a notifiable infectious disease in China but is a heavy burden on public health. However, the epidemic situation of EPTB nationwide is unclear. This study aimed to investigate the magnitude and main subtypes of EPTB in China. METHODS: We conducted a national cross-sectional study with multistage, stratified cluster random sampling during 2020-2021. We calculated proportions of EPTB in all patients with TB by organs. Logistic regression models were used to estimate odds ratios by characteristics. RESULTS: A total of 6843 patients with TB were included. Of them, 24.6% were patients with EPTB, and the proportion of EPTB solo was 21.3%. Higher EPTB burden was observed in children, female patients, clinically diagnosed patients, provincial-level and prefectural-level health facilities, and Central and West China. EPTB occurred most frequently in respiratory (35.5%), musculoskeletal (15.8%), and peripheral lymphatic (15.8%) systems with top three subtypes, including tuberculous pleurisy (35.0%), spinal TB (9.8%) and cervical tuberculous lymphadenopathy (7.9%). With the increase of age, proportion of peripheral lymphatic TB decreased, and proportion rank of genitourinary TB rose. CONCLUSION: It is essential to strengthen the diagnosis and treatment capacity for EPTB in primary medical facilities. EPTB should be added to the National Tuberculosis Program as a notifiable disease.

A four-generation family transmission chain of COVID-19 along the China-Myanmar border in October to November 2021.

Background: Foreign imported patients and within-household transmission have been the focus and difficulty of coronavirus disease 2019 (COVID-19) prevention and control, which has also posed challenges to border areas' management. However, household transmission caused by foreign imported cases has not been reported in China's border areas. This study aimed to reveal a clear family clustering transmission chain of COVID-19 caused by contact with Myanmar refugees along the China-Myanmar border during an outbreak in October to November 2021. Methods: During the outbreak, detailed epidemiological investigations were conducted on confirmed patients with COVID-19 and their close contacts in daily activities. Patients were immediately transported to a designated hospital for treatment and quarantine, and their close contacts were quarantined at designated sites. Regular nucleic acid testing and SARS-CoV-2 antibody testing were provided to them. Results: A clear four-generation family clustering transmission involving five patients with COVID-19 was found along the China-Myanmar border. The index case (Patient A) was infected by brief conversations with Myanmar refugees across border fences during work. His wife (Patient B) and 9-month-old daughter (Patient C) were second-generation cases infected by daily contact with him. His 2-year-old daughter (Patient D) was the third-generation case infected by her mother and sister during quarantine in the same room and then transmitted the virus to her grandmother (Patient E, the fourth-generation case) who looked after her after Patients B and C were diagnosed and transported to the hospital. The household secondary attack rate was 80.0%, the average latent period was 4 days, and the generation time was 3 days. Ten of 942 close contacts (1.1%) of this family had positive IgM antibody during the medical observation period. In total 73.9% (696/942) of them were positive for IgG antibody and 8.3% (58/696) had IgG levels over 20 S/CO (optical density of the sample/cut-off value of the reagent). Conclusion: This typical transmission chain indicated that it is essential to strengthen COVID-19 prevention and control in border areas, and explore more effective children care approaches in quarantine sites.

Risks, Epidemics, and Prevention Measures of Infectious Diseases in Major Sports Events: Scoping Review.

BACKGROUND: Major sports events are the focus of the world. However, the gathering of crowds during these events creates huge risks of infectious diseases transmission, posing a significant public health threat. OBJECTIVE: The aim of this study was to systematically review the epidemiological characteristics and prevention measures of infectious diseases at major sports events. METHODS: The procedure of this scoping review followed Arksey and O'Malley's five-step methodological framework. Electronic databases, including PubMed, Web of Science, Scopus, and Embase, were searched systematically. The general information (ie, publication year, study type) of each study, sports events' features (ie, date and host location), infectious diseases' epidemiological characteristics (ie, epidemics, risk factors), prevention measures, and surveillance paradigm were extracted, categorized, and summarized. RESULTS: A total of 24,460 articles were retrieved from the databases and 358 studies were included in the final data synthesis based on selection criteria. A rapid growth of studies was found over recent years. The number of studies investigating epidemics and risk factors for sports events increased from 16/254 (6.3%) before 2000 to 201/254 (79.1%) after 2010. Studies focusing on prevention measures of infectious diseases accounted for 85.0% (238/280) of the articles published after 2010. A variety of infectious diseases have been reported, including respiratory tract infection, gastrointestinal infection, vector-borne infection, blood-borne infection, and water-contact infection. Among them, respiratory tract infections were the most concerning diseases (250/358, 69.8%). Besides some routine prevention measures targeted at risk factors of different diseases, strengthening surveillance was highlighted in the literature. The surveillance system appeared to have gone through three stages of development, including manual archiving, network-based systems, and automated intelligent platforms. CONCLUSIONS: This critical summary and collation of previous empirical evidence is meaningful to provide references for holding major sports events. It is essential to improve the surveillance techniques for timely detection of the emergence of epidemics and to improve risk perception in future practice.

Discovery of Novel N-Heterocyclic-Fused Deoxypodophyllotoxin Analogues as Tubulin Polymerization Inhibitors Targeting the Colchicine-Binding Site for Cancer Treatment.

Natural products are a major source of anticancer agents and play critical roles in anticancer drug development. Inspired by the complexity-to-diversity strategy, novel deoxypodophyllotoxin (DPT) analogues were designed and synthesized. Among them, compound C3 exhibited the potent antiproliferative activity against four human cancer cell lines with IC50 values in the low nanomolar range. Additionally, it showed marked activity against paclitaxel-resistant MCF-7 cells and A549 cells. Moreover, compound C3 can inhibit tubulin polymerization by targeting the colchicine-binding site of tubulin. Further study revealed that compound C3 could arrest cancer cells in the G2/M phase and disrupt the angiogenesis in human umbilical vein endothelial cells. Meanwhile, C3 remarkably inhibited cancer cell motility and migration, as well as considerably inhibited tumor growth in MCF-7 and MCF-7/TxR xenograft model without obvious toxicity. Collectively, these results indicated that compound C3 may be a promising tubulin polymerization inhibitor development for cancer treatment.