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Enterovirus (EV)-associated hand, foot, and mouth disease (HFMD) is a significant public health issue worldwide, commonly occurring in children five years of age or younger. The leading causes of most HFMD cases are EVs, which are members of the Picornaviridae family. The typical clinical manifestations of EV-associated HFMD are febrile presentations with mucosal herpangina, oral ulcerations, and skin rashes on the hands and feet. The majority of HFMD cases resolve without consequence; however, a subset progresses to severe neurological and cardiopulmonary complications, which can be fatal. In the past two decades, EV-associated HFMD has received significant attention. In this review, we organize published papers and provide updates on epidemiology, pathogenesis, surveillance, and vaccine developments for EV-associated HFMD. The impact of EV-associated HFMD is increasing globally. Developing efficacious vaccines has become a priority for preventing EV infections without adequate treatment. Simultaneously, emerging EV infections (including EV-D68, EV-A71, Coxsackieviruses, and echoviruses) are increasing, highlighting the need to create a vigilant surveillance system for EV infections worldwide.

Background: Despite increasing awareness, silica dust-induced silicosis still contributes to the huge disease burden in China. Worryingly, recent silica dust exposure levels and silicosis risk in Chinese noncoal mines remain unclear., Objective: We aimed to determine recent silica dust exposure levels and assess the risk of silicosis in Chinese noncoal mines., Methods: Between May and December 2020, we conducted a retrospective cohort study on 3 noncoal mines and 1 public hospital to establish, using multivariable Cox regression analyses, prediction formulas of the silicosis cumulative hazard ratio (H) and incidence (I) and a cross-sectional study on 155 noncoal mines in 10 Chinese provinces to determine the prevalence of silica dust exposure (PDE), free silica content, and total dust and respirable dust concentrations. The qualitative risk of silicosis was assessed using the International Mining and Metals Commission's risk-rating table and the occupational hazard risk index; the quantitative risk was assessed using prediction formulas., Results: Kaplan-Meier survival analysis revealed significant differences in the silicosis probability between silica dust-exposed male and female miners (log-rank test χ21=7.52, P=.01). A total of 126 noncoal mines, with 29,835 miners and 4623 dust samples, were included; 13,037 (43.7%) miners were exposed to silica dust, of which 12,952 (99.3%) were male. The median PDE, free silica content, total dust concentration, and respirable dust concentration were 61.6%, 27.6%, 1.30 mg/m3, and 0.58 mg/m3, respectively, indicating that miners in nonmetal, nonferrous metal, small, and open-pit mines suffer high-level exposure to silica dust. Comprehensive qualitative risk assessment showed noncoal miners had a medium risk of silicosis, and the risks caused by total silica dust and respirable silica dust exposure were high and medium, respectively. When predicting H and I over the next 10, 20, and 30 years, we assumed that the miner gender was male. Under exposure to current total silica dust concentrations, median I10, I20, and I30 would be 6.8%, 25.1%, and 49.9%, respectively. Under exposure to current respirable silica dust concentrations, median I10, I20, and I30 would be 6.8%, 27.7%, and 57.4%, respectively. These findings showed that miners in nonmetal, nonferrous metal, small, and open-pit mines have a higher I and higher qualitative silicosis risk., Conclusions: Chinese noncoal miners, especially those in nonmetal, nonferrous metal, small, and open-pit mines, still suffer high-level exposure to silica dust and a medium-level risk of silicosis. Data of both total silica dust and respirable silica dust are vital for occupational health risk assessment in order to devise effective control measures to reduce noncoal mine silica dust levels, improve miners' working environment, and reduce the risk of silicosis., (©Kai Liu, Xin Sun, Wei-Jiang Hu, Liang-Ying Mei, Heng-Dong Zhang, Shi-Biao Su, Kang Ning, Yun-Feng Nie, Le-Ping Qiu, Ying Xia, Lei Han, Qiang Zhi, Chun-Bo Shi, Geng Wang, Wei Wen, Jian-Qiong Gao, Bing Yu, Xin Wang, Yi-Wen Dong, Ning Kang, Feng Han, Hong-Ying Bian, Yong-Qing Chen, Meng Ye. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 02.09.2024.)

Coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is an emergent disease that threatens global health. Public health structures and economic activities have been disrupted globally by the COVID-19 pandemic. Over 556.3 million confirmed cases and 6.3 million deaths have been reported. However, the exact mechanism of its emergence in humans remains unclear. SARS-CoV-2 is believed to have a zoonotic origin, suggesting a spillover route from animals to humans, which is potentially facilitated by wildlife farming and trade. The COVID-19 pandemic highlighted the importance of the One Health approach in managing threats of zoonosis in the human-animal-environment interaction. Implementing vigilant surveillance programs by adopting the One Health concept at the interfaces between wildlife, livestock, and humans is the most pertinent, practical, and actionable strategy for preventing and preparing for future pandemics of zoonosis, such as COVID-19 infection. This review summarizes the updated evidence of CoV infections in humans and animals and provides an appropriate strategy for preventive measures focused on surveillance systems through an On Health approach., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Leprosy is an infectious disease that remains a public health concern. It is caused by acid-fast Bacillus leprae, which primarily affects the skin and peripheral nerves, potentially leading to long-term disability and stigma. However, current and previous efforts have focused on developing better diagnostic and therapeutic interventions for leprosy, and its prevention needs to be addressed. In this review, we organize the currently published papers and provide updates on the global epidemiology, diagnosis, treatment, and prevention of leprosy. Several online databases, including MEDLINE (National Library of Medicine, Bethesda, MD), PubMed, EMBASE, Web of Science, and Google Scholar, were searched to collect relevant published papers. As a public health issue, the World Health Organization set the goal of leprosy elimination with a prevalence of <1 case per 10,000 people, which was achieved in 2000 and in most countries by 2010, mainly owing to the treatment of leprosy using drugs starting in 1980 and no-cost access for patients since 1995. Although diagnostic and therapeutic techniques have improved, the new occurrence of leprosy remains a critical global disease burden. With continuous technological improvements in diagnosing and treating leprosy, obtaining more relevant healthcare knowledge and preventing leprosy disability are crucial., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Heat-related illness (HRI) is commonly considered an acute condition, and its potential long-term consequences are not well understood. We conducted a population-based cohort study and an animal experiment to evaluate whether HRI is associated with dementia later in life., Methods: The Taiwan National Health Insurance Research Database was used in the epidemiological study. We identified newly diagnosed HRI patients between 2001 and 2015, but excluded those with any pre-existing dementia, as the study cohort. Through matching by age, sex, and the index date with the study cohort, we selected individuals without HRI and without any pre-existing dementia as a comparison cohort at a 1:4 ratio. We followed each cohort member until the end of 2018 and compared the risk between the two cohorts using Cox proportional hazards regression models. In the animal experiment, we used a rat model to assess cognitive functions and the histopathological changes in the hippocampus after a heat stroke event., Results: In the epidemiological study, the study cohort consisted of 70,721 HRI patients and the comparison cohort consisted of 282,884 individuals without HRI. After adjusting for potential confounders, the HRI patients had a higher risk of dementia (adjusted hazard ratio [AHR] = 1.24; 95% confidence interval [CI]: 1.19-1.29). Patients with heat stroke had a higher risk of dementia compared with individuals without HRI (AHR = 1.26; 95% CI: 1.18-1.34). In the animal experiment, we found cognitive dysfunction evidenced by animal behavioral tests and observed remarkable neuronal damage, degeneration, apoptosis, and amyloid plaque deposition in the hippocampus after a heat stroke event., Conclusions: Our epidemiological study indicated that HRI elevated the risk of dementia. This finding was substantiated by the histopathological features observed in the hippocampus, along with the cognitive impairments detected, in the experimental heat stroke rat model., (© 2024. The Author(s).)

Introduction: Photokeratoconjunctivitis (PKC) is primarily caused by welding. However, inappropriate use of germicidal lamps, which have been widely used following the COVID-19 outbreak, can also cause PKC. Our goal in this study was to investigate the incidence of and changes in the causes of PKC during the coronavirus 2019 (COVID-19) pandemic., Methods: We conducted a single-center, retrospective observational study. The health records of patients who visited the emergency department in a tertiary care hospital from January 1, 2018-December 31, 2021 and were diagnosed with PKC, were reviewed. We then conducted an analysis to compare the characteristics of PKC before and after COVID-19 began and the features of PKC caused by welding and germicidal lamps., Results: There were 160 PKC cases with a clear etiology before the COVID-19 pandemic and 147 cases during the COVID-19 pandemic. No significant differences in age and gender were detected between the two groups. The incidence of PKC induced by the use of germicidal lamps during the COVID-19 pandemic was significantly higher (10.2%) than the incidence before the pandemic (3.1%). The ratio of females to males in the germicidal lamp subgroup was significantly higher than the ratio in the welding subgroup. Limitations included incomplete information due to the retrospective nature of the study, underestimation of incidence, and possible recall bias., Conclusion: In the era of COVID-19, clinicians should be aware of the hazards of germicidal lamps. Although the COVID-19 pandemic seems to show signs of easing, new infectious diseases that require protective measures could still emerge in the future. Therefore, injuries related to germicidal lamps deserve more public health attention., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

This study retrospectively analyzed the medical records of 602 patients with first-time positive results for the HCV nucleic acid test between 1 May 2021 and 31 March 2023, exploring the association between DAA treatment and SARS-CoV-2 infection. The results showed that 9.8% of HCV patients were co-infected with SARS-CoV-2. Gender, age, vaccination status, and HCV genotype did not significantly affect SARS-CoV-2 infection. However, patients undergoing DAA treatment showed significantly lower rates of SARS-CoV-2 infection and mortality compared to those not undergoing DAA treatment. The analysis also compared patients undergoing different DAA treatments, with Epclusa and Maviret showing superior protection against SARS-CoV-2. Furthermore, this study explored the severity and mortality of SARS-CoV-2 infection in patients undergoing and having completed DAA treatment. It revealed that patients diagnosed with COVID-19 during DAA treatment experienced only mild symptoms, and none died, suggesting a potential protective effect of DAA treatment against severe outcomes of SARS-CoV-2 infection. The findings contribute to the understanding of the interplay between HCV, DAA treatment, and SARS-CoV-2 infection, highlighting the need for continued monitoring and healthcare measures for individuals with chronic conditions during the ongoing COVID-19 pandemic.

Objective: To analyze factors influencing the underestimation of noise-induced permanent threshold shift (NIPTS) among manufacturing workers, providing baseline data for revising noise exposure standard., Design: A cross-sectional study was designed with 2702 noise-exposed workers from 35 enterprises from 10 industries. Personal noise exposure level(L Aeq,8h ) and noise kurtosis level were determined by a noise dosimeter. Questionnaires and hearing loss tests were performed for each subject. The predicted NIPTS was calculated using the ISO 1999:2013 model for each participant, and the actual measured NIPTS was corrected for age and sex. The factors influencing the underestimation of NIPTS were investigated., Results: The predicted NIPTS at each test frequency (0.5, 1, 2, 3, 4, or 6kHz) and mean NIPTS at 2, 3, 4, and 6kHz (NIPTS 2346 ) using the ISO 1999:2013 model were significantly lower than their corresponding measured NIPTS, respectively (P < 0.001). The ISO model significantly underestimated the NIPTS 2346 by 12.36 dB HL. The multiple linear regression analysis showed that noise exposure level, exposure duration, age, and kurtosis could affect the degree of underestimation of NIPTS 2346 . The generalized additive model (GAM) with (penalized) spline components showed nonlinear relationships between critical factors (age, exposure duration, noise level, and kurtosis) and the underestimated NIPTS 2346 .The underestimated NIPTS 2346 decreased with an increase in exposure duration (especially over ten years). There was no apparent trend in the underestimated NIPTS 2346 with age. The underestimated NIPTS 2346 decreased with the increased noise level [especially > 90 dB(A)]. The underestimated NIPTS 2346 increased with an increase in noise kurtosis after adjusting for the noise exposure level and exposure duration and ultimately exhibiting a linear regression relationship., Conclusions: The ISO 1999 predicting model significantly underestimated the noise-induced hearing loss among manufacturing workers. The degree of underestimation became more significant at the noise exposure condition of fewer than ten years, less than 90 dB(A), and higher kurtosis levels. It is necessary to apply kurtosis to adjust the underestimation of hearing loss and consider the applying condition of noise energy metrics when using the ISO predicting model., (© 2023. The Author(s).)

The hepatitis B virus (HBV) is one of the major viral infection problems worldwide in public health. The exclusive proprietary Chinese medicine Ganweikang (GWK) tablet has been marketed for years in the treatment of chronic hepatitis B (CHB). However, the pharmacodynamic material basis and underlying mechanism of GWK are not completely clear. This study is aimed at investigating the pharmacological mechanism of the GWK tablet in the treatment of CHB. The chemical ingredient information was obtained from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID), and Shanghai Institute of Organic Chemistry of CAS. Ingredients and disease-related targets were defined by a combination of differentially expressed genes from CHB transcriptome data and open-source databases. Target-pathway-target (TPT) network analysis, molecular docking, and chemical composition analysis were adopted to further verify the key targets and corresponding active ingredients of GWK. Eight herbs of GWK were correlated to 330 compounds with positive oral bioavailability, and 199 correlated targets were identified. The TPT network was constructed based on the 146 enriched targets by KEGG pathway analysis, significantly associated with 95 pathways. Twenty-five nonvolatile components and 25 volatile components in GWK were identified in UPLC-QTOF/MS and GC-MS chromatograms. The key active ingredients of GWK include ferulic acid, oleanolic acid, ursolic acid, tormentic acid, 11-deoxyglycyrrhetic acid, dibenzoyl methane, anisaldehyde, wogonin, protocatechuic acid, psoralen, caffeate, dimethylcaffeic acid, vanillin, β -amyrenyl acetate, formonentin, aristololactam IIIa, and 7-methoxy-2-methyl isoflavone, associated with targets CA2, NFKB1, RELA, AKT1, JUN, CA1, CA6, IKBKG, FOS, EP300, CREB1, STAT1, MMP9, CDK2, ABCB1, and ABCG2., Competing Interests: Authors CY Chen and ZM Cao are employed at Jiaheng (Hengqin, Zhuhai) Pharmaceutical Technology Co., Ltd. Author JL Guan is employed at Henan Fusen Pharmaceutical Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jia-Qi Xu et al.)

Background: Previous studies that compared the postoperative health-related quality of life (HRQoL) outcomes after receiving laparoscopic resection (LR) or open resection (OR) in patients with colorectal cancer (CRC) have different conclusions., Aim: To explore the medium-term effect of postoperative HRQoL in such patients., Methods: This study randomized 567 patients undergoing non-metastatic CRC surgery managed by one surgeon to the LR or OR groups. HRQoL was assessed during the preoperative period and 3, 6, and 12 mo postoperative using a modified version of the 36-Item Short Form (SF-36) Health Survey questionnaire, emphasizing eight specific items., Results: This cohort randomly assigned 541 patients to receive LR ( n = 296) or OR ( n = 245) surgical procedures. More episodes of postoperative urinary tract infection ( P < 0.001), wound infection ( P < 0.001), and pneumonia ( P = 0.048) were encountered in the OR group. The results demonstrated that the LR group subjectively gained mildly better general health ( P = 0.045), moderately better physical activity ( P = 0.006), and significantly better social function recovery ( P = 0.0001) 3 mo postoperatively. Only the aspect of social function recovery was claimed at 6 mo, with a significant advantage in the LR group ( P = 0.001). No clinical difference was found in HRQoL during the 12 mo., Conclusion: Our results demonstrated that LR resulted in better outcomes, including intra-operative blood loss, surgery-related complications, course of recovery, and especially some health domains of HRQoL at least within 6 mo postoperatively. Patients should undergo LR if there is no contraindication., Competing Interests: Conflict-of-interest statement: All authors declare that we have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study aimed to compare the SARS-CoV-2 nucleic acid detection results of the BD MAX™ System and other platforms to formulate an optimized laboratory verification process. The re-examination of 400 samples determined as positive by BD MAX™ indicated that the inconsistency rate between BD MAX™ and the other platforms was 65.8%; the inconsistency rate of single-gene-positive results was as high as 99.2%. A receiver operating characteristic curve was drawn for the relative light unit (RLU) values of samples positive for a single gene, and RLU 800 was used as the cutoff. After setting the retest standard as single-gene positive and RLU ≥ 800, the number of the 260 BD MAX™ single-gene positives that needed to be confirmed again was 36 (13.8%) and the number that could be directly reported as negative was 224 (86.2%). This verification process can shorten the reporting period and speed up the epidemic adjustment time and turnover rate of special wards, thereby improving SARS-CoV-2 detection efficiency and clinical decision-making.

Coronavirus disease 2019 (COVID-19) might affect cancer treatment outcomes. This systematic review and meta-analysis identified the prognostic predictors of adult patients with hematologic malignancies and COVID-19, and evaluated the effect of anticancer therapy on mortality. We performed a literature search of electronic databases and identified additional studies from the bibliographies of the articles that were retrieved. Two investigators independently extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. We evaluated study quality using the Newcastle-Ottawa Scale and performed a meta-analyses in order to evaluate the effect of anticancer therapy on mortality among adult patients with hematologic malignancies and COVID-19. Heterogeneity was assessed with the I 2 statistic. The meta-analysis included 12 studies. The overall mortality rate was 36.3%. The pooled risk difference (RD) in mortality between patients receiving and not receiving anticancer therapy was 0.14 (95% confidence interval [CI]: 0.02-0.26; I 2 = 76%). The pooled RD in mortality associated with chemotherapy was 0.22 (95% CI: 0.05-0.39; I 2 = 48%), and with immunosuppression was 0.20 (95% CI: 0.05-0.34; I 2 = 67%). In the subgroup analyses, anticancer-therapy-associated mortality was higher in females (RD = 0.57; 95% CI: 0.29-0.85; I 2 = 0%) than in males (RD = 0.28; 95% CI: 0.04-0.52; I 2 = 0%). Among patients with hematologic malignancies and COVID-19, those receiving anticancer therapy had a higher mortality risk, regardless of sex. The mortality risk was higher in females than in males. These results indicate that caution should be exercised when administering anticancer therapy to patients with hematologic malignancies and COVID-19.

Introduction: Breast cancer (BC) is the most common cancer in women worldwide. Because of the extended survival of patients with BC, the occurrence of second primary malignancies (SPMs) after BC is an important issue., Methods: We identified female patients with BC in the Breast Cancer Health Database of Taiwan, which includes four cancer registry datasets between 2002 and 2014 from Taiwan Cancer Registry. We compared the incidence of SPM between patients who received chemotherapy and/or radiotherapy with those who did not. Stratified analyses were performed according to the American Joint Committee on Cancer (AJCC) stage. The Cox regression model was used to identify the risk factors for SPM and evaluate their effects., Results: We enrolled 85,947 eligible patients with BC, and 2,656 (3.09%) patients developed SPM. The median duration of SPM was 2.70 (1.14-5.14) years. Radiotherapy was administered in 40,946 (47.64%) patients, and chemotherapy was administered in 52,120 (60.64%). The most common SPMs were digestive tract cancers (876, 31.89%). The risk factors for SPM included the AJCC stage, chemotherapy, radiotherapy, age, and underlying comorbidities. Neither chemotherapy nor radiotherapy was associated with an increased risk of SPM in any stage. In contrast, after adjusting for other risk factors, patients at stage III/IV who received both therapies had lower risks of SPM compared with those who did not ( p = 0.047)., Conclusion: The risk of SPM was different across BC stages. Neither chemotherapy nor radiotherapy was associated with an increased risk of SPM in women with BC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Hsiao, Huang, Tsao, Ho, Su and Guo.)

Sleep quality is directly correlated with overall health and quality of life. Firefighters have a higher workload and injury rate than those in other occupations. This study investigated the prevalence of and risk factors for poor sleep quality among firefighters in Taiwan. This cross-sectional study was conducted between November 2019 and August 2020. Sociodemographic information of the study participants was collected using a structured self-administered questionnaire. The Chinese version of the Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the subjective sleep quantity and quality of firefighters during the previous month. A t test for continuous variables and χ2 test for categorical variables were performed for univariate analysis. Logistic regression analysis was conducted for multivariate analysis. Eight hundred eighty-nine firefighters completed the questionnaire during the study period, with a response rate of 88.9%. Among them, 447 (50.3%) reported poor sleep quality. Logistic regression analysis showed that female sex, longer work duration (>5 years) for firefighters, on-call shift work, and no leisure-time physical activity (LTPA) was significantly correlated with an increased risk of poor sleep quality. Advanced analysis of partaking in LTPA revealed that high-intensity LTPA is significantly associated with higher rates of poor sleep quality. In contrast, adequate rest after LTPA correlated with lower rates of poor sleep quality. Firefighters are at higher risk of poor sleep quality. Emphasis should be placed on firefighters' regular LTPA, particularly when experiencing sleep problems., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Carbon monoxide poisoning may damage the brain and adrenal glands, but it is unclear whether it is associated with adrenal insufficiency. We identified all COP patients diagnosed between 1999 and 2012 in Taiwan using the Nationwide Poisoning Database and selected a reference cohort (participants without COP) from the same database by exact matching of age and index date at a 1:2 ratio. Participants with a history of adrenal insufficiency or steroid use of more than 14 days were excluded. We followed up participants until 2013 and compared the risk of developing adrenal insufficiency between the two cohorts. The 21,842 COP patients had a higher risk for adrenal insufficiency than the 43,684 reference participants (adjusted hazard ratio [AHR] = 2.5; 95% confidence interval [CI]: 1.8-3.5) after adjustment for sex and underlying comorbidities (liver disease, thyroid disease, mental disorder). The risk continued to elevate even after 1 year (AHR = 2.1; 95% CI: 1.4-3.4). The COP patients who had acute respiratory failure had an even higher risk for adrenal insufficiency than those without acute respiratory failure, which may indicate a dose-response relationship. Stratified analyses showed that female patients had an elevated risk (AHR = 3.5; 95% CI: 2.1-6.0), but not male patients. Younger patients (< 50 years) had higher risks, and the AHR reached statistical significance in the age groups 20-34 (AHR = 5.5; 95% CI: 1.5-20.6) and 35-49 (AHR = 4.9; 95% CI: 2.3-10.6) years old. The risk for developing adrenal insufficiency elevated after COP, especially in female and younger patients. Carbon monoxide is the most common gaseous agent causing acute intoxication worldwide. Results of the current study call for monitoring adrenal function of patients with COP., (© 2022. The Author(s).)

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has emerged as a global health concern. This study aimed to review the epidemiology and pathophysiology of COVID-19 and provide evidence for the implementation of control measures. We utilized several online databases, including MEDLINE (National Library of Medicine, Bethesda, Maryland, USA), PubMed, EMBASE, Web of Science, and Google Scholar, to collect relevant published papers using a combination of the following keywords: "COVID-19," "SARS-CoV-2," "novel coronavirus," "epidemiology," and "pathophysiology." The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used in this study. Globally, approximately 3-46% of patients with SARS-CoV-2 infection experience gastrointestinal symptoms. The clinical spectrum of COVID-19 is wide, ranging from mild to severe, and even fatal. COVID-19 was initially reported as a respiratory tract disease; however, gastrointestinal symptoms have only recently been reported. COVID-19 Patients with gastrointestinal symptoms may have more severe clinical manifestations and poor prognosis. This study highlights the need to better understand the mechanisms involved in the development of gastrointestinal symptoms in patients with COVID-19 to prevent the further spread of this pathogen., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Leprosy is a neglected infectious disease caused by acid-fast bacillus Mycobacterium leprae . It primarily affects the skin and then progresses to a secondary stage, causing peripheral neuropathy with potential long-term disability along with stigma. Leprosy patients account for a significant proportion of the global disease burden. Previous efforts to improve diagnostic and therapeutic techniques have focused on leprosy in adults, whereas childhood leprosy has been relatively neglected. This review aims to update the diagnostic and therapeutic recommendations for adult and childhood leprosy. This review summarizes the clinical, bacteriological, and immunological approaches used in the diagnosis of leprosy. As strategies for the diagnosis and management of leprosy continue to develop better and more advanced knowledge, control and prevention of leprosy are crucial., Competing Interests: The authors declared no conflicts of interest., (Copyright © 2022 Kou-Huang Chen et al.)

Background: Breast cancer (BC) is the most common malignant cancer in women. A predictive model is required to predict the 5-year survival in patients with BC (5YSPBC) and improve the treatment quality by increasing their survival rate. However, no reports in literature about apps developed and designed in medical practice to classify the 5YSPBC. This study aimed to build a model to develop an app for an automatically accurate classification of the 5YSPBC., Methods: A total of 1810 patients with BC were recruited in a hospital in Taiwan from the secondary data with codes on 53 characteristic variables that were endorsed by professional staff clerks as of December 31, 2019. Five models (i.e., revolution neural network [CNN], artificial neural network, Naïve Bayes, K-nearest Neighbors Algorithm, and Logistic regression) and 3 tasks (i.e., extraction of feature variables, model comparison in accuracy [ACC] and stability, and app development) were performed to achieve the goal of developing an app to predict the 5YSPBC. The sensitivity, specificity, and receiver operating characteristic curve (area under ROC curve) on models across 2 scenarios of training (70%) and testing (30%) sets were compared. An app predicting the 5YSPBC was developed involving the model estimated parameters for a website assessment., Results: We observed that the 15-variable CNN model yields higher ACC rates (0.87 and 0.86) with area under ROC curves of 0.80 and 0.78 (95% confidence interval 0.78-82 and 0.74-81) based on 1357 training and 540 testing cases an available app for patients predicting the 5YSPBC was successfully developed and demonstrated in this study., Conclusion: The 15-variable CNN model with 38 parameters estimated using CNN for improving the ACC of the 5YSPBC has been particularly demonstrated in Microsoft Excel. An app developed for helping clinicians assess the 5YSPBC in clinical settings is required for application in the future., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Context: Xiaoyaosan decoction (XYS), a classical Traditional Chinese Medicine (TCM) formula is used to treat liver fibrosis in clinics., Objective: This study explores defined compound combinations from XYS decoction to treat liver fibrosis., Materials and Methods: Network pharmacology combined with transcriptomics analysis was used to analyze the XYS decoction and liver depression and spleen deficiency syndrome liver fibrosis. From the constructed XYS-Syndrome-liver fibrosis network, the top 10 active formulas were developed by topological analysis according to network stability. The most active formula was determined by in vitro study. The anti-fibrosis effect was evaluated by in vitro and in vivo studies., Results: According to the network XYS-Syndrome-liver fibrosis network, 8 key compounds and 255 combinations were predicted from in XYS. Luteolin, licochalcone A, aloe-emodin and acacetin formula (LLAAF) had a synergistic effect on the proliferation inhibition of hepatic stellate cells compared to individual compounds alone. The treatment of XYS and LLAAF showed a similar anti-liver fibrotic effect that reduced histopathological changes of liver fibrosis, Hyp content and levels of α-SMA and collagen I in CCl 4 -induced liver fibrosis in rats. Transcriptomics analysis revealed LLAAF regulated PI3K-Akt, AMPK, FoxO, Jak-STAT3, P53, cell cycle, focal adhesion, and PPAR signalling. Furthermore, LLAAF was confirmed to regulate Jak-STAT and PI3K-Akt-FoxO signalling in vitro and in vivo ., Conclusions: This study developed a novel anti-liver formula LLAAF from XYS, and demonstrated its anti-liver fibrotic activity which may be involved in the regulation of Jak-STAT and PI3K-Akt-FoxO signalling.

Abstract: Mumps is an acute and common childhood disease caused by paramyxovirus. It has been reported that the occurrence of mumps is influenced by seasonality. However, the role of meteorological variables in the incidence of mumps remains unclear. The purpose of this study was to explore the relationship between meteorological factors and the incidence of mumps infection. Poisson regression analysis was used to study the relationship between weather variability and the incidence of mumps in Taiwan. Between 2012 and 2018, 5459 cases of mumps cases were reported to the Centers for Disease Control, Taiwan (Taiwan CDC). The occurrence of mumps virus infections revealed significant seasonality in the spring and summer seasons in Taiwan. The incidence of mumps virus infections began to increase at temperatures of 15°C and started to decline if the temperature was higher than 29°C (r2 = 0.387, P = .008). Similarly, the number of mumps cases began to increase at a relative humidity of 65% to 69% (r2 = 0.838, P < .029). The number of mumps cases was positively associated with temperature and relative humidity during the period preceding the infection. This study showed that the occurrence of mumps is significantly associated with increasing temperature and relative humidity in Taiwan. Therefore, these factors could be regarded as early warning signals and indicate the need to strengthen the intervention and prevention of mumps., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 ( p < 0.05), and increased the expression of E-cadherin ( p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues ( p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

There is a lack of effective therapeutic drugs in patients with postoperative colorectal cancer (PCRC). This study aimed to investigate the therapeutic effect and mechanisms of Bushen-Jianpi-Jiedu decoction (BSJPJDD) combined with chemotherapeutic drugs (oxaliplatin) on PCRC with liver and kidney yin deficiency and spleen deficiency syndrome (LKYD-SDS) through the therapeutic evaluation of clinical therapy and the integrative analysis of network pharmacology, RNA-seq and label-free data, and experiment verification in vitro . In clinical therapy, the median progression-free survival (PFS) and Karnofsky performance score (KPS) were increased in PCRC patients by the aqueous extract of BSJPJDD combined with oxaliplatin treatment for three months, compared to oxaliplatin alone ( p < 0.05). The integrative analysis showed that 559 differentially expressed genes (DEGs) and 11 differentially expressed proteins (DEPs) were regulated by BSJPJDD, among which seven bioactive compounds through 39 potential targets were involved in the regulation of multiple signaling pathways including MAPK, PI3K-Akt, and HIF-1, etc. In the experimental verification, an ELISA assay showed that plasma ZEB2, CAT, and KRT78 were decreased, and IL-1Α, CD5L, FBLN5, EGF, and KRT78 were increased in comparison to the above ( p < 0.05). Furthermore, the SW620 cell viability was inhibited and the expressions of MAPK and the p-ERK/ERK ratio were significantly downregulated by the aqueous extract of BSJPJDD combined with oxaliplatin treatment, compared with oxaliplatin treatment alone ( p < 0.05). These data suggested that BSJPJDD combined with oxaliplatin prolongs the survival and improves Karnofsky performance status of PCRC patients with LKYD-SDS, and may be associated with the regulation of multiple signaling pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Zhou, Chen, Chen, Ji, Li, Wang and Su.)

The COVID-19 pandemic has spread widely around the world. Many mathematical models have been proposed to investigate the inflection point (IP) and the spread pattern of COVID-19. However, no researchers have applied social network analysis (SNA) to cluster their characteristics. We aimed to illustrate the use of SNA to identify the spread clusters of COVID-19. Cumulative numbers of infected cases (CNICs) in countries/regions were downloaded from GitHub. The CNIC patterns were extracted from SNA based on CNICs between countries/regions. The item response model (IRT) was applied to create a general predictive model for each country/region. The IP days were obtained from the IRT model. The location parameters in continents, China, and the United States were compared. The results showed that (1) three clusters (255, n = 51, 130, and 74 in patterns from Eastern Asia and Europe to America) were separated using SNA, (2) China had a shorter mean IP and smaller mean location parameter than other counterparts, and (3) an online dashboard was used to display the clusters along with IP days for each country/region. Spatiotemporal spread patterns can be clustered using SNA and correlation coefficients (CCs). A dashboard with spread clusters and IP days is recommended to epidemiologists and researchers and is not limited to the COVID-19 pandemic.

Background: Because of the limited information available regarding peripheral vertigo (PV) in physicians, we conducted this study to clarify this issue., Methods: We used Taiwan National Health Insurance Research Database to identify 26,309 physicians and an identical number of general population matched by age and sex. All the participants who had PV before 2007 and residents were excluded. By tracing their medical histories between 2007 and 2013, comparisons of PV risk between physicians and general population and among physicians were performed., Results: Physicians had a significantly lower PV risk than the general population (adjusted odds ratio [AOR]: 0.811; 95% confidence interval [CI]: 0.662-0.994). In comparison among physicians, otolaryngologists had a significantly higher PV risk than other specialties. Physicians who were older or served in local hospitals or clinics had a significantly higher PV risk than physicians in medical centers., Conclusion: Physicians had a significantly lower PV risk than the general population. Better medical knowledge in physicians than in the general population may explain the findings; however, further studies are warranted for elucidating the detailed mechanisms., Competing Interests: Conflicts of interest No conflicts of interest were declared., (Copyright © 2021 Huang et al. Published by Tehran University of Medical Sciences.)

Occupational noise-induced hearing loss (ONIHL) is the most prevalent occupational disease in the world. The goal of this study was to review the epidemiology, pathogenesis, and preventive measures of ONIHL among workers and provide evidence for the implementation of control measures. Literature studies were identified from the MEDLINE, PubMed, Embase, Web of Science, and Google Scholar using the search terms "noise-induced hearing loss" "prevalence", "pathogenesis", and "preventive measures". The articles reviewed in this report were limited from 2000 to 2020. Articles that were not published in the English language, manuscripts without an abstract, and opinion articles were excluded. After a preliminary screening, all of the articles were reviewed and synthesized to provide an overview of the current status of ONIHL among workers. The mechanism of ONIHL among workers is a complex interaction between environmental and host factors (both genetic and acquired factors). The outcomes of noise exposure are different among individual subjects. Clinical trials are currently underway to evaluate the treatment effect of antioxidants on ONIHL. Noise exposure may contribute to temporary or permanent threshold shifts; however, even temporary threshold shifts may predispose an individual to eventual permanent hearing loss. Noise prevention programs are an important preventive measure in reducing the morbidity of ONIHL among workers.

Hepatitis B virus (HBV) infection is an important factor causing hepatocellular carcinoma (HCC). The aim of this study was to investigate the metabolic characteristics and related metabolic enzyme changes during the progression from chronic hepatitis B (CHB) to liver cirrhosis (LC) and, ultimately, to HCC. An untargeted metabolomics assay was performed in plasma from 50 healthy volunteers, 43 CHB patients, 67 LC patients, and 39 HCC patients. A total of 24 differential metabolites (DMs) were identified. Joint pathway analysis suggested striking changes in amino acid metabolism and lipid metabolism from CHB to HCC. The panel of L-serine, creatine and glycine distinguished LC from CHB, and L-serine, cystathionine, creatine and linoleic acid distinguished HCC from LC. Bioinformatic analysis of publicly available data showed that differential metabolite profile-associated enzyme genes, including alanine-glyoxylate aminotransferase-2 ( AGXT2 ), D-amino-acid oxidase ( DAO ), and cystathionine gamma-lyase ( CTH ), were downregulated, while bisphosphoglycerate mutase ( BPGM ), cystathionine-β-synthase ( CBS ), phosphoserine phosphatase ( PSPH ) and acyl-CoA thioesterase 7 ( ACOT7 ) were upregulated, in HCC, all of which correlated with a poor prognosis for HCC patients. Our results indicated that serum metabolites and related enzymes are of considerable significance for the diagnosis and prognosis of HCC and can provide a theoretical basis and therapeutic index for future diagnosis and treatment.

Glycyrrhetinic acid (GA), a hydrolysate of glycyrrhizic acid from licorice root extract, has been used to treat liver fibrotic diseases. However, the molecular mechanism involved in the antifibrotic effects of GA remains unclear. The involvement of miR-663a and its roles in TGF- β -1-induced hepatic stellate cell (HSC) activation remains unclear. In this study, we investigated the roles of miR-663a in the activation of HSCs and the antifibrosis mechanism of GA. MiR-663a expression was downregulated in TGF- β -treated HSCs. The overexpression of miR-663a inhibited HSC proliferation. TGF- β -1was confirmed as a direct target gene of miR-663a. MiR-663a alleviated HSC activation, concomitant with decreased expression of α -smooth muscle actin ( α -SMA), human α 2 (I) collagen (COL1A2), TGF- β 1, TGF- β RI, Smad4, p-Smad2, and p-Smad3. GA upregulated miR-663a expression and inhibited the TGF- β /Smad pathway in HSCs. Further studies showed that miR-663a inhibitor treatment reversed GA-mediated downregulation of TGF- β 1, TGF- β RI, Smad4, p-Smad2, p-Smad3, α -SMA, and CoL1A2 in TGF- β 1-treated HSCs. These results show that miR-663a suppresses HSC proliferation and activation and the TGF- β /Smad signaling pathway, highlighting that miR-663a can be utilized as a therapeutic target for hepatic fibrosis. GA inhibits, at least in part, HSC proliferation and activation via targeting the miR-663a/TGF- β /Smad signaling pathway., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Xin-Xin Guo et al.)

Mumps is an important childhood infectious disease caused by mumps virus (MuV). We reviewed the epidemiology, pathogenesis, and vaccine development of mumps. Previous studies were identified using the key words "mumps" and "epidemiology", "pathogenesis" or "vaccine" in MEDLINE, PubMed, Embase, Web of Science, and Google Scholar. We excluded the articles that were not published in the English language, manuscripts without abstracts, and opinion articles from the review. The number of cases caused by MuV decreased steeply after the introduction of the mumps vaccine worldwide. In recent years, a global resurgence of mumps cases in developed countries and cases of aseptic meningitis caused by some mumps vaccine strains have renewed the importance of MuV infection worldwide. The performance of mumps vaccination has become an important issue for controlling mumps infections. Vaccine development and routine vaccination are still effective measures to globally reduce the incidence of mumps infections. During outbreaks, a third of MMR vaccine is recommended for groups of persons determined by public authorities., Competing Interests: The authors declare no conflicts of interest exist.

Carbon monoxide poisoning (COP) may cause injuries to the central nervous and endocrine systems, which might increase the risk of developing hypothyroidism. We wanted to evaluate the association between COP and the risk of developing hypothyroidism because epidemiological data on this potential association are limited. We conducted a nationwide population-based cohort study using the Nationwide Poisoning Database and identified 24,328 COP subjects diagnosed between 1999 and 2012. By matching the index date and age, we selected 72,984 non-COP subjects for comparison. Subjects with thyroid diseases and malignancy before 1999 were excluded. We followed up the two groups of subjects until 2013 and compared the risk of developing hypothyroidism. COP subjects had a significantly higher risk for hypothyroidism than non-COP subjects (adjusted hazard ratio [AHR]: 3.8; 95% confidence interval [CI]: 3.2-4.7) after adjusting for age, sex, underlying comorbidities, and monthly income, and the AHR was particular higher in subjects with diabetes mellitus, hyperlipidemia, and mental disorder. The increased risk was highest in the first month after COP (AHR: 41.0; 95% CI: 5.4-310.6), and the impact remained significant even after 4 years. In conclusion, COP was associated with an increased risk for hypothyroidism. Further studies regarding the underlying mechanisms are warranted.

The epithelial-to-mesenchymal transition (EMT) plays a prominent role in cancer metastasis. Isoliquiritigenin (ISL), one of the flavonoids in licorice, has been shown to exhibit anticancer activities in many cancer types through various mechanisms. However, it is unknown whether ISL impacts the EMT process. Here, we show that ISL is able to suppress mesenchymal features of ovarian cancer SKOV3 and OVCAR5 cells, evidenced by an apparent morphological change from a mesenchymal to an epithelial phenotype and reduced levels of mesenchymal markers accompanied by the gain of E-cadherin expression. The suppression of EMT is also supported by the observed decrease in cell migration and in vitro invasion upon ISL treatment. Moreover, we show that ISL effectively blocks the intraperitoneal xenograft development of the SKOV3 cell line and prolonged the survival of tumor-bearing mice. These data suggest that ISL inhibits intraperitoneal ovary tumor development through the suppression of EMT, indicating that ISL may be an effective therapeutic agent against ovarian cancer.

The study was conducted to explore the mechanisms of sex differences in the response to chronic hepatitis B (CHB) in terms of DNA methylation, SNP genotype, and gene expression. Genomic DNA was isolated from peripheral blood mononuclear cells (PBMCs) of CHB patients and healthy controls and evaluated using the Human Methylation 450 K Assay. The DNA methylation level at hg37 chromosome (CHR) X: 7810800 was further validated using pyrosequencing. SNP genotypes, VCX mRNA expression of PBMCs, and plasma VCX protein concentration were further examined using SNaPshot, RT-qPCR, and Western blot, respectively. Results showed that a total of 5529 CpG loci were differentially methylated between male and female CHB patients. DNA methylation level and CC + CT frequency at CHR X: 7810800, VCX mRNA expression of PBMCs, and plasma VCX protein concentration were higher in female than in male CHB patients. The CHR X: 7810800 locus was hypermethylated in CHB patients with CC + CT genotypes in comparison with those with the TT genotype. In cases of CC + CT genotypes, VCX mRNA expression was negatively correlated with the DNA methylation level. CHB patients with higher levels of HBV DNA, AST, and GGT or higher GPRI scores exhibited lower VCX expression. In conclusion, SNPs and DNA methylation at the CHR X: 7810800 locus cooperatively regulate VCX expression in CHB. The upregulated VCX expression in female CHB patients might represent a mechanism of protection from more severe liver dysfunction and extensive fibrosis, as observed in male CHB patients.

Background: Many authors are concerned which types of peer-review articles can be cited most in academics and who were the highest-cited authors in a scientific discipline. The prerequisites are determined by: (1) classifying article types; and (2) quantifying co-author contributions. We aimed to apply Medical Subject Headings (MeSH) with social network analysis (SNA) and an authorship-weighted scheme (AWS) to meet the prerequisites above and then demonstrate the applications for scholars., Methods: By searching the PubMed database (pubmed.com), we used the keyword "Medicine" [journal] and downloaded 5,636 articles published from 2012 to 2016. A total number of 9,758 were cited in Pubmed Central (PMC). Ten MeSH terms were separated to represent the journal types of clusters using SNA to compare the difference in bibliometric indices, that is, h, g, and x as well as author impact factor(AIF). The methods of Kendall coefficient of concordance (W) and one-way ANOVA were performed to verify the internal consistency of indices and the difference across MeSH clusters. Visual representations with dashboards were shown on Google Maps., Results: We found that Kendall W is 0.97 (χ = 26.22, df = 9, P < .001) congruent with internal consistency on metrics across MeSH clusters. Both article types of methods and therapeutic use show higher frequencies than other 8 counterparts. The author Klaus Lechner (Austria) earns the highest research achievement(the mean of core articles on g = Ag = 15.35, AIF = 21, x = 3.92, h = 1) with one paper (PMID: 22732949, 2012), which was cited 23 times in 2017 and the preceding 5 years., Conclusion: Publishing article type with study methodology and design might lead to a higher IF. Both classifying article types and quantifying co-author contributions can be accommodated to other scientific disciplines. As such, which type of articles and who contributes most to a specific journal can be evaluated in the future.

Liver fibrosis is the common pathological basis of all chronic liver diseases, and is the necessary stage for the progression of chronic liver disease to cirrhosis. As one of pathogenic factors, inflammation plays a predominant role in liver fibrosis via communication and interaction between inflammatory cells, cytokines, and the related signaling pathways. Damaged hepatocytes induce an increase in pro-inflammatory factors, thereby inducing the development of inflammation. In addition, it has been reported that inflammatory response related signaling pathway is the main signal transduction pathway for the development of liver fibrosis. The crosstalk regulatory network leads to hepatic stellate cell activation and proinflammatory cytokine production, which in turn initiate the fibrotic response. Compared with the past, the research on the pathogenesis of liver fibrosis has been greatly developed. However, the liver fibrosis mechanism is complex and many pathways involved need to be further studied. This review mainly focuses on the crosstalk regulatory network among inflammatory cells, cytokines, and the related signaling pathways in the pathogenesis of chronic inflammatory liver diseases. Moreover, we also summarize the recent studies on the mechanisms underlying liver fibrosis and clinical efforts on the targeted therapies against the fibrotic response., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest.

The aim of this study was to investigate the alterations of urinary microRNA (miRNA) expression and explore its clinical significance in patients with chronic hepatitis B (CHB).The expression levels of urinary miRNA were detected by miRNA microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 106 CHB and 40 healthy controls (Ctrl) subjects. The correlation between the levels of miRNA expression and clinical characteristics were analyzed. Receiver-operator characteristic (ROC) curves were generated to determine the specificity and sensitivity of each individual miRNA. MiRNAs expression were further measured by PCR from exosomes, which were isolated from urine samples. LX2 cells were transfected with miRNA inhibitor and accumulation of cytoplasmic lipid droplets was analyzed by Oil Red O staining.miRNA expression profile analysis showed that 22 miRNAs were upregulated and 55 miRNAs were downregulated in CHB patients compared with Ctrl subjects (fold-change>1.5 and P < .05). miR-92b-3p, miR-770-5p, miR-5196-5p, and miR-7855-5p were significantly higher (P < .0001) in CHB subjects than in Ctrl subjects. ROC curve analysis showed that these four miRNAs were sensitive and specific enough to distinguish CHB and Ctrl subjects. The levels of miR-92b-3p expression were negatively correlated with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and APOA-1. Moreover, in vitro experiments indicated that inhibition of miR-92b-3p increased lipid droplet formation in LX2 cells.Aberrant expression of miRNAs has been observed in urine of CHB patients. Our findings may provide novel insights into the pathogenesis of CHB and may assist in the diagnosis of patients with CHB.

The oncologic merits of the laparoscopic technique for colorectal cancer surgery remain debatable. Eligible patients with non-metastatic colorectal cancer who were scheduled for an elective resection by one surgeon in a medical institution were randomized to either laparoscopic or open surgery. During this period, a total of 188 patients received laparoscopic surgery and the other 163 patients received the open approach. The primary endpoint was cancer-free five-year survival after operative treatment, and the secondary endpoint was the tumor recurrence incidence. Besides, surgical complications were also compared. There was no statistically significant difference between open and laparoscopic groups regarding the average number of lymph nodes dissected, ileus, anastomosis leakage, overall mortality rate, cancer recurrence rate, or cancer-free five-year survival. Even though performing a laparoscopic approach used a significantly longer operation time, this technique was more effective for colorectal cancer treatment in terms of shorter hospital stay and less blood loss. Meanwhile, fewer patients receiving the laparoscopic approach developed postoperative urinary tract infection, wound infection, or pneumonia, which reached statistical significance. For non-metastatic colorectal cancer patients, laparoscopic surgery resulted in better short-term outcomes, whether in several surgical complications and intra-operative blood loss. Though there was no significant statistical difference in terms of cancer-free five-year survival and tumor recurrence, it is strongly recommended that patients undergo laparoscopic surgery if not contraindicated.

Yinchenhao decoction (YCHD) is a classical Traditional Chinese Medicine (TCM) formula that has been widely used in the treatment of liver fibrosis caused by chronic hepatitis B and jaundice for more than 1800 years. The purpose of this study was to investigate the apoptosis regulation mechanisms of YCHD and its active components suppresses liver fibrosis. The active components and putative targets of YCHD were predicted by network pharmacology approach. Functional and pathway enrichment analysis were presented in the present study by using clusterProfiler. Further, experimental validation was done by using terminal deoxynucleotidyl transferase (TDT) dUTP nick end labelling (TUNEL) assay and western blotting in dimethylnitrosamine (DMN)-induced liver fibrosis rats, and cell proliferation assay, apoptosis assay, and western blotting in human hepatic L02 cells and LX2 cells. 45 active compounds in YCHD formula, 592 potential target proteins and 1191 liver fibrosis-related human genes were identified. Functional and pathway enrichment analysis indicated that YCHD obviously influenced TNF, PI3K-Akt signaling pathways. Further, In vivo experiment indicated that YCHD treatment not only attenuated the symptoms of liver fibrosis, but also decrease the apoptosis of hepatic parenchyma cells. Moreover, in vitro experiments showed that rhein, kaempferol and quercetin treatments remarkably decreased the protein levels of cleaved caspase-3 and increased p-ERK1/2, PI3K and Bcl-XL protein expression in TNF-α-stimulated L02 cells. On the contrary, rhein, kaempferol, aloe-emodin and quercetin inhibited the proliferation of LX2 cells and up-regulated the protein levels of Bax and cleaved caspase-8. In conclusion, 45 active components and 296 potential targets of YCHD against liver fibrosis were identified by the analysis of network pharmacology and transcriptomics combination. The mechanisms of YCHD against liver fibrosis were involved in the regulation of multiple targets, especially affecting the apoptosis-related signaling pathways., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Prolonged static postures (PSPs) may predispose dentists to develop cervical herniated intervertebral disc (C-HIVD); however, there is limited evidence supporting this in the literature thus far. We conducted this study to fit the data gap., Methods: We conducted a retrospective nationwide population-based study using the Taiwan National Health Insurance Research Database to identify 10,930 dentists, an identical number of age- and sex-matched participants from the general population, and 73,718 other health care providers (HCPs, non-dentists). Comparisons for the risk of developing C-HIVD between dentists and the general population, and between dentists and other HCPs were performed by tracing their medical histories between 2007 and 2011., Results: Dentists had a cumulative incidence rate of 1.1% for C-HIVD during the 5-year follow-up period. Overall, there was no difference of the risk for C-HIVD between dentists and the general population after adjusting for hypertension, hyperlipidemia, liver disease, mental disorders, diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease, malignancy, stroke, and renal disease (adjusted odds ratio [AOR]: 1.2, 95% confidence interval [CI]: 0.9-1.6). However, stratified analysis showed that younger dentists (≤ 34 years) had a trend of higher risk for C-HIVD than members of the younger general population (AOR: 1.9, 95% CI: 0.9-4.1). There was no difference found between dentists and other HCPs (AOR: 0.9, 95% CI: 0.8-1.1)., Conclusion: Younger dentists had a trend of higher risk of developing C-HIVD than members of the general population.

Objectives: Dentists may have a higher risk of developing lumbar herniated intervertebral disc (HIVD) due to prolonged sitting and improper postures during work. We conducted this study to delineate this issue, which is still unclear., Methods: This nationwide population-based study was conducted using Taiwan National Health Insurance Research Database. We identified 10 734 dentists, 72 066 non-dentist health-care providers (HCPs), and an identical number of age- and gender-matched participants from the general population. The risk of developing lumbar HIVD among dentists, non-dentist HCPs, and general population was compared by tracing their medical histories between 2007 and 2011., Results: The cumulative incidence rate of lumbar HIVD among dentists during the 5-year follow-up period was 1.40%. After adjusting for age, gender, and comorbidities, the risk of developing lumbar HIVD was found to be lower among dentists than that among the general population (adjusted odds ratio [AOR]: 0.80, 95% confidence interval [CI]: 0.64-1.00) and non-dentist HCPs (AOR: 0.81, 95% CI: 0.68-0.96)., Conclusions: Dentists in Taiwan have a lower risk of developing lumbar HIVD than that among other occupations. Although this result is different from the general cognition, it does not imply that the prevention of lumbar HIVD in dentists is not important. Further studies are warranted to better address this issue., (© 2019 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Liver diseases cause serious public health problems because of their high global prevalence and poor long-term clinical outcomes. With its mild and broad therapeutic efficacy, traditional Chinese medicine (TCM) has played an important role in the prevention and treatment of liver diseases in China for hundreds of years. Tanshinone IIA (TIIA), a major component extracted from the traditional herbal medicine Salvia miltiorrhiza Bunge, has been broadly studied for its multiple biological activities, including antiangiogenic, antioxidant, anti-inflammatory and anticancer properties. In this article, we focus on the effects of TIIA on the development of liver diseases, including hepatic injury, fatty liver, hepatic fibrosis and hepatocellular carcinoma (HCC), as well as the mechanism underlying TIIA and its new formulations and carriers in order to provide a reference for its further study and clinical therapeutic use in liver diseases., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Metastasis is a major cause of death in patients with breast cancer. In the process of cancer development, epithelial-mesenchymal transition (EMT) is crucial to promoting the invasion and migration of tumor cells. In a previous study, the role of resveratrol in migration and metastasis was investigated in MDA-MB-231 (MDA231) human breast cancer cells and a xenograft-bearing mouse model. Additionally, the related mechanism was explored. In the present study, in vitro Transwell assays showed that resveratrol can inhibit the migration of transforming growth factor (TGF)-β1-induced MDA231 cells in a concentration-dependent manner. An enzyme-linked immunosorbent assay (ELISA) showed that resveratrol can reduce the secretion of matrix metalloproteinase (MMP)-2 and MMP-9. Immunofluorescence was performed to confirm the expression of EMT-related markers. Immunofluorescence assays confirmed that resveratrol changed the expression of the EMT-related markers E-cadherin and vimentin. Western blot analysis demonstrated that resveratrol decreased the expression levels of MMP-2, MMP-9, Fibronectin, α-SMA, P-PI3K, P-AKT, Smad2, Smad3, P-Smad2, P-Smad3, vimentin, Snail1, and Slug, as well as increased the expression levels of E-cadherin in MDA231 cells. In vivo, resveratrol inhibited lung metastasis in a mouse model bearing MDA231 human breast cancer xenografts without marked changes in body weight or liver and kidney function. These results indicate that resveratrol inhibits the migration of MDA231 cells by reversing TGF-β1-induced EMT and inhibits the lung metastasis of MDA231 human breast cancer in a xenograft-bearing mouse model., Competing Interests: The author(s) confirm that this article content has no conflict of interest.

To investigate the mechanism of a Bushen-Jianpi decoction (BSJPD) in liver cancer (LC) treatment, we analyzed clinical therapy data, conducted network pharmacology analysis, and performed pharmacological experimental verification in vitro and in vivo . The univariate analysis of clinical therapy showed that the BSJPD was protective factor ( p < 0.05). The network pharmacology analysis showed that 9 compounds were important nodes of BSJPD-LC therapy network. In experimental verification, the rate of apoptosis increased in the liver tumors of mice treated with the BSJPD ( p < 0.05); drug serum with 20 % BSJPD inhibited cell viability ( p < 0.05) and reduced the expression of PI3K, the Bcl-xL/BAD ratio, and the levels of p53 and p-Akt in HepG2 cells. Moreover, licochalcone A, alisol B, and hederagenin inhibited cell viability ( p < 0.05), induced cell apoptosis ( p < 0.01), reduced p-Akt levels, and increased cleaved-CASP3 ( p < 0.05) and p53 expression levels in HepG2 cells. These data suggest that the BSJPD prolongs the survival of LC patients and induces apoptosis and that it may be associated with the regulation of PI3K, Akt, p53, CASP3, and Bcl-xL/BAD expression.

Mounting evidence has shown that long noncoding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) in distinct physiological and pathological states. The activation of hepatic stellate cells (HSCs) is a critical event in the development of hepatic fibrosis (HF). LncRNAs have recently been revealed to be involved in HSC activation as ceRNAs. CeRNA analysis tremendously expands the functional information of proteins, DNA and coding and noncoding RNA. In addition, many validated ceRNA networks, including the traditional ceRNA/mRNA/miRNA, participate in the initiation and progress of HF, and additional work is needed in elucidating the potential of ceRNAs in precancer diagnosis, prognosis and providing new therapeutic methods for HF reversion., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Fuzheng huayu formula (FZHY), an antifibrotic traditional Chinese medicine, is frequently used for the treatment of liver fibrosis. In this study, network analysis, transcriptomic analysis, assays of cell apoptosis, viability and protein expression were used for investigating the effects and mechanisms of compounds derived from FZHY on hepatic parenchymal cell (HPC) protection and hepatic stellate cell activation. Network pharmacology analysis found that 6 major compounds and 39 potential targets were important network nodes. Our analysis predicted that the active compounds of FZHY, including hederagenin, luteolin and tanshinone IIA inhibited cell apoptosis ( p < 0.05), increased PI3K expression and reduced cleaved caspase 3 expression and the Bax/Bcl-w ratio ( p < 0.05) in L02 cells that had apoptosis induced by TNF-α. Few significant changes caused by FZHY, hederagenin, luteolin and tanshinone IIA were observed in hepatic stellate Lx2 cells upon TGF-β1 induction. These data suggest that FZHY is active against liver fibrosis, protects hepatic parenchymal cells from apoptosis, and recovers liver function, possibly through the effects of its active compounds hederagenin, luteolin and tanshinone IIA and is involved in the inhibition of apoptosis in HPCs, possibly through regulating the PI3K, ERK, cleaved caspase 3 and Bax/Bcl-w levels.

Systems biology is an academic field that attempts to integrate different levels of information to understand how biological systems function. It is the study of the composition of all components of a biological system and their interactions under specific conditions. The core of systems biology is holistic and systematic research, which is different from the manner of thinking and research of all other branches of biology to date. Chinese herbal formulae (CHF) are the main form of Chinese medicine and are composed of single Chinese herbal medicines (CHMs) with pharmacological and pharmacodynamic compatibility. When single CHMs are combined into CHF, the result is different from the original effect of a single drug and can be better adapted to more diseases with complex symptoms. CHF represent a complex system with multiple components, targets and effects. Therefore, the use of systems biology is conducive to revealing the complex characteristics of CHF. With the rapid development of omics technologies, systems biology has been widely and increasingly applied to the study of the basis of the pharmacological substances, action targets and mechanisms of CHF. To meet the challenges of multiomics synthesis-intensive studies and system dynamics research in CHF, this paper reviews the common techniques of genomics, transcriptomics, proteomics, metabolomics, and metagenomics and their applications in research on CHF.

The management of dengue fever (DF) has been suggested to be categorized into decision groups A, B, and C; however, its usefulness in predicting mortality is still unclear, and hence we conducted this study to clarify this issue. We conducted a study by recruiting 2,358 patients with DF from the 2015 outbreak in the Chi-Mei Medical Center. Demographic data, vital signs, clinical symptoms and signs, coexisting morbidities, laboratory data, decision groups categorized according to World Health Organization for clinical management of dengue in 2012, and 30-day mortality rates were included for analysis. The overall 30-day mortality rate was 1.4%. The 30-day mortality rates in decision groups A, B, and C were 0%, 0.5%, and 46.2%, respectively. Compared with Group A, there was a higher mortality risk in Group C (odds ratio [OR]: 1,480, 95% confidence interval [CI]: 195-11,200). The area under the curve of the variable of Group C was excellent (OR: 0.92, 95% CI: 0.85-0.99). The sensitivity, specificity, positive predictive value, and negative predictive value for predicting 30-day mortality in Group C were 88.2%, 98.5%, 46.2%, and 99.8%, respectively. This study showed that decision Group C has a good predictive value for 30-day mortality. Further studies including validation in other nations are warranted.

Yinchenhao decoction (YCHD), comprising Yinchenhao (Artemisiae Scopariae Herba), Zhizi (Gardeniae Fructus) and Dahuang (Radix Rhei et Rhizoma), is widely used for treating various diseases. We aimed to investigate the bile acid metabolic mechanism of YCHD in dimethylnitrosamine (DMN)-induced liver fibrosis model. Rats received DMN (10 mg/kg, intraperitoneally) for four successive weeks for liver fibrosis induction and were treated with YCHD for the last 2 weeks. Histopathological analysis showed that YCHD prevented DMN-induced histopathological changes in liver tissues. Serum liver function in YCHD group improved. Ultraperformance liquid chromatography-mass spectrometry analysis showed that YCHD significantly restored both free and conjugated bile acid levels increased by DMN, to normal levels. RT-qPCR results showed that YCHD treatment upregulated the expression of genes related to bile acid synthesis, reabsorption, and excretion. Western blotting analysis showed that YCHD downregulated α-SMA, TGF-β1, p-Smad3, and p-ERK1/2 expression in chenodeoxycholic acid (CDCA)-activated hepatic stellate cells (HSCs). The viability of CDCA-activated HSCs significantly increased after treatment with YCHD and PD98059 (an ERK inhibitor) compared to YCHD treatment alone. Our findings suggest that YCHD alleviated DMN-induced liver fibrosis by regulating enzymes responsible for bile acid metabolism. Additionally, it inhibits CDCA-induced HSC proliferation and activation via TGF-β1/Smad/ERK signalling pathway.

Background: Licorice is an herb extensively used for both culinary and medicinal purposes. Various constituents of licorice have been shown to exhibit anti-tumorigenic effect in diverse cancer types. However, majority of these studies focus on the aspect of their growth-suppressive role. In this study, we systematically analyzed known licorice's constituents on the goal of identifying component(s) that can effectively suppress both cell migration and growth., Methods: Effect of licorice's constituents on cell growth was evaluated by MTT assay while cell migration was assessed by both wound-healing and Transwell assays. Cytoskeleton reorganization and focal adhesion assembly were visualized by immunofluorescence staining with labeled phalloidin and anti-paxillin antibody. Activity of Src in cells was judged by western blot using phosphor-Src416 antibody while Src kinase activity was measured using Promega Src kinase assay system. Anti-tumorigenic capabilities of isoliquiritigenin (ISL) and 2, 4, 2', 4'-Tetrahydroxychalcone (THC) were investigated using lung cancer xenograft model., Results: Using a panel of lung cancer cell lines, ISL was identified as the only licorice's constituent capable of inhibiting both cell migration and growth. ISL-led inhibition in cell migration resulted from impaired cytoskeleton reorganization and focal adhesion assembly. Assessing the phosphorylation of 141 cytoskeleton dynamics-associated proteins revealed that ISL reduced the abundance of Tyr421-phosphorylation of cortactin, Tyr925- and Tyr861-phosphorylation of FAK, indicating the involvement of Src because these sites are known to be phosphorylated by Src. Enigmatically, ISL inhibited Src in cells while displayed no effect on Src activity in cell-free system. The discrepancy was explained by the observation that THC, one of the major ISL metabolite identified in lung cancer cells abrogated Src activity both in cells and cell-free system. Similar to ISL, THC deterred cell migration and abolished cytoskeleton reorganization/focal adhesion assembly. Furthermore, we showed both ISL and THC suppressed in vitro lung cancer cell invasion and in vivo tumor progression., Conclusion: Our study suggests that ISL inhibits lung cancer cell migration and tumorigenesis by interfering with Src through its metabolite THC. As licorice is safely used for culinary purposes, our study suggests that ISL or THC may be safely used as a Src inhibitor.

Nurses have high work stress that may contribute to an increased overdose for sedatives, hypnotics, and antipsychotics (OSHA). We conducted this nationwide population-based cross-sectional study to clarify this still unclear issue. We used a nationwide database to identify 110,379 nurses, 22,032 other healthcare providers (HCPs), and an identical number of individuals from the general population matched by age and sex. We compared the period prevalence of OSHA between nurses and the general population, other HCPs and the general population, and nurses and other HCPs, among nurse subgroups from 2006 to 2012. The risk for OSHA in nurses and in the general population was not significantly different after adjusting for anxiety, insomnia, depression, schizophrenia, and affective disorders (adjusted odds ratio [AOR]: 1.145; 95% confidence interval [CI]: 0.974-1.346). However, in the age subgroups < 35 years, nurses had higher risk than the general population of having OSHA (AOR: 1.333; 95% CI: 1.109-1.601). Other HCPs had a significantly lower risk for OSHA than the general population (AOR: 0.237; 95% CI: 0.122-0.460). Nurses had a significantly higher risk for OSHA than other HCPs (AOR: 3.902; 95% CI: 2.159-7.048). Comparison among nurses showed that younger nurses (< 35 years) had a significantly higher risk for OSHA than the older nurses (≥ 50 years) (AOR: 3.569; 95% CI: 1.252-10.330). Registered nurses had significantly higher risk for OSHA than registered professional nurses (AOR: 1.810; 95% CI: 1.405-2.332); and nurses from clinics, local hospitals, and regional hospitals had significantly higher risk than nurses from medical centers. This study delineated that nurses had a nearly four-fold risk for OSHA when compared to other HCPs. Younger nurses, registered nurses, and nurses from clinics, local hospitals, and regional hospitals had higher risks for OSHA than their respective nurse controls; it suggests that more attention should be given to the occupational health of these populations., Competing Interests: The authors have declared that no competing interests exist.

Liver fibrosis is a consequence of chronic liver disease that can progress to liver cirrhosis or even hepatocarcinoma. Fuzheng Huayu (FZHY), a Chinese herbal formula, has been shown to exert anti-fibrotic effects. To better understand the molecular mechanisms underlying the anti-fibrotic effects of FZHY, we analyzed transcriptomic and proteomic combination profiles in CCl 4 -induced liver fibrosis in rats, which were treated with extracted FZHY powder (0.35 g·kg -1 ·d -1 , ig) for 3 weeks. We showed that FZHY administration significantly improved liver function, alleviated hepatic inflammatory and fibrotic changes, and decreased the hydroxyproline content in the livers of CCl 4 -treated rats. When their liver tissues were examined using microarray and iTRAQ, we found 255 differentially expressed genes (fold change ≥1.5, P<0.05) and 499 differentially expressed proteins (fold change ≥1.2, P<0.05) in the FZHY and model groups. Functional annotation with DAVID (The Database for Annotation, Visualization and Integrated Discovery) showed that 15 enriched gene ontology terms, including drug metabolic process, response to extracellular stimulus, response to vitamins, arachidonic acid metabolic process, response to wounding, and oxidation reduction might be involved in the anti-fibrotic effects of FZHY; whereas KEGG pathway analysis revealed that eight enriched pathways, including arachidonic acid metabolism, retinol metabolism, metabolism of xenobiotics by cytochrome P450, and drug metabolism might also be involved. Moreover, the protein-protein interaction network demonstrated that 10 core genes/proteins overlapped, with Ugt2a3, Cyp2b1 and Cyp3a18 in retinol metabolism pathway overlapped to a higher degree. Compared to the model rats, the livers of FZHY-treated rats had significantly higher mRNA and protein expression levels of Ugt2a3, Cyp2b1 and Cyp3a18. Furthermore, the concentration of retinoic acid was significantly higher in the FZHY-treated rats compared with the model rats. The results suggest that the anti-fibrotic effects of FZHY emerge through multiple targets, multiple functions, and multiple pathways, including FZHY-regulated retinol metabolism, xenobiotic metabolism by cytochrome P450, and drug metabolism through up-regulated Ugt2a3, Cyp2b1, and Cyp3a18. These genes may play important anti-fibrotic roles in FZHY-treated rats.

Fuzheng-Huayu formula (FZHY), a Chinese herbal mixture prescription, has been proven effective in treating liver fibrosis and cirrhosis in both clinical trials and animal experiments. In this study we assessed the metabolic mechanisms of traditional Chinese medicine (TCM) syndrome-based FZHY treatment in liver cirrhosis (LC). A total of 113 participants, including 50 healthy controls and 63 LC patients, were recruited. According to the diagnosis and differentiation of the TCM syndromes, the LC patients were classified into 5 TCM syndrome groups including the liver stagnation syndrome (LSS), spleen deficiency and damp overabundance syndrome (SDDOS), damp-heat accumulation syndrome (DHAS), liver-kidney Yin deficiency syndrome (LKYDS), and blood stagnation syndrome (BSS), and administered FZHY for 6 months. FZHY treatment significantly decreased serum levels of hyaluronic acid (HA), a biochemical marker for LC, as well as TCM syndrome scores (the TCM syndrome scores were decreased in all the groups with significant decreases in the LSS and LKYDS groups). Furthermore, FZHY treatment gradually shifted the metabolic profiles of LC patients from a pathologic state to a healthy state, especially in LC patients with LSS and LKYDS. Twenty-two differently altered metabolites (DAMs) were identified, including carbohydrates, amino acids, fatty acids, etc with 9 DAMs in LSS patients, 9 in LKYDS patients, and 4 in other patients. The metabolic pathways involved in the conversion of amino acids and the body's detoxification process were regulated first, followed by the pathways involved in the body's energy supply process. In conclusion, the evaluation of the effect of TCM syndrome-based FZHY treatment show that FZHY has a better effect on LKYDS and LSS than on the other TCM syndromes, and the metabolic mechanisms might be involved in the increased detoxification function in LKYDS and the improvement of energy supply in LSS, which provides important evidence for the clinical application of TCM syndrome-based treatment.