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This study examines tuberculosis (TB) incidence among students in Jilin Province, China, focusing on spatial, temporal, and demographic dynamics in areas of social inequality. Variation in incidence rate of TB was analyzed using the joinpoint regression method. Spatial analyses techniques included the global and local Moran indices and Getis-Ord Gi* analysis. Demographic changes in new cases were analyzed descriptively, and the Geodetector method measured the influence of risk factors on student TB incidence. The analysis revealed a declining trend in TB cases, particularly among male students. TB incidence showed geographical heterogeneity, with lower rates in underdeveloped rural areas compared to urban regions. Significant spatial correlations were observed, with high-high clusters forming in central Jilin Province. Hotspots of student TB transmission were primarily concentrated in the southwestern and central regions from 2008 to 2018. Socio-economic factors exhibited nonlinear enhancement effects on incidence rates, with a dominant bifactor effect. High-risk zones were predominantly located in urban centers, with university and high school students showing higher incidences than other educational stages. The study revealed economic determinants as being especially important in affecting TB incidence among students, with these factors having nonlinear interacting effects on student TB incidence., (© 2024. The Author(s).)

Objective: Delays in the diagnosis and treatment of pulmonary tuberculosis (PTB) can increase the risk of transmission, thereby posing a significant risk to public health. Early diagnosis is considered to play a crucial role in eliminating TB. Rapid testing, active case finding, and health education are effective strategies for reducing tuberculosis diagnosis delays (TDDs). This study aimed to quantitatively compare the impact of reducing the TDD on incidence rates among student and non-student groups, thus exploring the efficacy of shortening the TDD for ending the TB epidemic and providing a reference for achieving the target incidence rate for ending TB., Methods: We used unsupervised hierarchical clustering analysis and non-parametric tests to characterize the epidemiological characteristics of TDD. Additionally, a dynamic transmission model was used to quantify the impact of shortening the TDD on the incidence rates of TB among the two groups., Results: There was an initial increase in the TDD, followed by a decrease. Longer TDDs were observed in the northeastern region of China. Farmers, middle and high school students, middle-aged, elderly individuals and males exhibited relatively longer TDDs. A significant reduction in the incidence rate of PTB was observed when the TDD was decreased by 50 %. However, only reducing the TDD among non-students could achieve the goal of ending TB (i.e., achieving a minimum reduction of 63.00 %)., Conclusions: TDD remains a serious risk to public health, and non-students were shown to experience longer TDD. Shortening the TDD is crucial for reducing the incidence rates of TB, especially among non-students. It is essential to develop a highly sensitive and effective system for eliminating TB among non-students., 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. Published by Elsevier Ltd.)

The creation of a Z-scheme heterojunction is a sophisticated strategy to enhance photocatalytic efficiency. In our study, we synthesized an In 2 S 3 /MnO 2 /BiOCl dual Z-scheme heterostructure by growing BiOCl nanoplates on the sheets of In 2 S 3 nanoflowers, situated on the surface of MnO 2 nanowires. This synthesis involved a combination of hydrothermal and solution combustion methods. Experiments and density functional theory (DFT) calculations demonstrated that the In 2 S 3 /MnO 2 /BiOCl composite exhibited notable photo reduction performance and photocatalytic stability. This was attributed to the pivotal roles of BiOCl and MnO 2 in the composite, acting as auxiliaries to enhance the electronic structure and facilitate the adsorption/activation capacity of CO 2 and H 2 O. The yield rates of CO, CH 4 , and C 2 H 4 over In 2 S 3 /MnO 2 /BiOCl as the catalyst were 3.94, 5.5, and 3.64 times higher than those of pure In 2 S 3 , respectively. Photoelectrochemical analysis revealed that the dual Z-scheme heterostructure, with its oxygen vacancies and large surface area, enhanced CO 2 absorption and active sites on the nanoflower/nanowire intersurfaces. Consequently, the dual Z-scheme charge transfer pathway provided efficient channels for boosting electron transfer and charge separation, resulting in high C 2 H 4 , CH 4 , and CO yields of formed and exihibits an promising photoreduction rate of CO 2 to CO (51.2 µmol/g.h), CH 4 (42.4 µmol/g.h) and C 2 H 4 (63.2 µmol/g.h), respectively. DFT, in situ Diffuse reflectance infrared fourier transform spectroscopy, and temperature-programmed desorption tests were employed to verify the intermediates pathway. The study proposed a potential photocatalytic mechanism based on these findings., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The integration of structural magnetic resonance imaging (sMRI) and deep learning techniques is one of the important research directions for the automatic diagnosis of Alzheimer's disease (AD). Despite the satisfactory performance achieved by existing voxel-based models based on convolutional neural networks (CNNs), such models only handle AD-related brain atrophy at a single spatial scale and lack spatial localization of abnormal brain regions based on model interpretability. To address the above limitations, we propose a traceable interpretability model for AD recognition based on multi-patch attention (MAD-Former). MAD-Former consists of two parts: recognition and interpretability. In the recognition part, we design a 3D brain feature extraction network to extract local features, followed by constructing a dual-branch attention structure with different patch sizes to achieve global feature extraction, forming a multi-scale spatial feature extraction framework. Meanwhile, we propose an important attention similarity position loss function to assist in model decision-making. The interpretability part proposes a traceable method that can obtain a 3D ROI space through attention-based selection and receptive field tracing. This space encompasses key brain tissues that influence model decisions. Experimental results reveal the significant role of brain tissues such as the Fusiform Gyrus (FuG) in AD recognition. MAD-Former achieves outstanding performance in different tasks on ADNI and OASIS datasets, demonstrating reliable model interpretability.

Introduction: Differences in transmissibility of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) in different districts are hard to assess. To address this, our study focused on calculating the Real-time reproduction number ( R t ) for these variants in different regions., Methods: According to the criteria defined by the World Health Organization (WHO), the global landscape was categorized into six distinct regions. In each region, the predominant SARS-CoV-2 variant was first identified based on the proportion of variant sequencing analysis results. Then, using serial interval (SI) parameters, we calculated R t for the relevant Variant of Concern (VOC) in each region. This approach enabled us to compare the R t values of the same variant across different regions and analyze the transmissibility of each region's variant in relation to the overall situation in that region., Results: The progression of VOC for SARS-CoV-2 shows regional variations. However, a common sequence of evolution is observed: Wild-type → Alpha → Beta → Delta → Omicron. Moreover, an increasing trend is discerned within diverse regions where the shift in R t of distinct VOC corresponds with the overarching R t route of SARS-CoV-2 in specific regions., Conclusion: As the COVID-19 pandemic advances, regional epidemiological trends are aligning, likely due to similar virus mutations and shared public health strategies, suggesting opportunities for standardized global responses., 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.)

Purpose: Polygala tenuifolia Willd. (PT), a traditional Chinese medicinal plant extensively employed in managing Alzheimer's disease, exhibits notable gastrointestinal side effects as highlighted by prior investigations. In contrast, Magnolia officinalis Rehd. et Wils (MO), a traditional remedy for gastrointestinal ailments, shows promising potential for ameliorating this adverse effect of PT. The objective of this study is to examine the underlying mechanism of MO in alleviating the side effects of PT., Methods: Hematoxylin-eosin (H&E) staining was used to observe the structural damage of zebrafish intestine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors and oxidative stress. The integrity of the intestinal tight junctions was examined using transmission electron microscope (TEM). Moreover, the expression of intestinal barrier genes and PI3K/AKT/NF-κB signaling pathway-related genes was determined through quantitative real-time PCR. The changes in intestinal microbial composition were analyzed using 16S rRNA and metagenomic techniques., Results: MO effectively ameliorated intestinal pathological damage and barrier gene expression, and significantly alleviated intestinal injury by reducing the expression of inflammatory cytokines IL-1β, IL-6, TNF-α, and inhibiting the activation of PI3K/AKT/NF-κB pathway. Furthermore, MO could significantly increase the relative abundance of beneficial microorganisms ( Lactobacillus, Blautia and Saccharomyces cerevisiae ), and reduce the relative abundance of pathogenic bacteria ( Plesiomonas and Aeromonas )., Conclusion: MO alleviated PT-induced intestinal injury, and its mechanism may be related to the inhibition of PI3K/AKT/NF-κB pathway activation and regulation of intestinal flora., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Liu et al.)

What Is Already Known About This Topic?: Given the challenges presented by drug-resistant strains of tuberculosis (TB) and the rising mobility of the population, achieving the objective of eradicating TB appears uncertain., What Is Added by This Report?: The examination of TB incidence trends in 10 high-burden countries (HBCs) indicated a steady rise in cases, with India and China jointly accounting for nearly 70% of the burden. Projections for the future show diverse trajectories in these countries, with potential difficulties in reaching the TB elimination target, especially in Nigeria, Congo, and South Africa., What Are the Implications for Public Health Practice?: The number of TB cases is on the rise. It is crucial to learn from successful strategies to improve TB prevention and control worldwide through collaborative efforts., Competing Interests: The funder had no role in the study design, data collection and analysis, decision to publish, or manuscript preparation. No other conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2024.)

Background: To evaluate the cost-effectiveness of Tislelizumab vs Sorafenib as the first-line treatment of unresectable hepatocellular carcinoma (HCC) from the perspective of the Chinese health service system., Methods: A lifetime partitioned survival model (PSM) was developed to cost-effectively analyze Tislelizumab vs Sorafenib as the first-line treatment of unresectable HCC. The clinical and safety data were derived from a recently randomized clinical trial (RATIONALE-301). Utilities were collected from the published literature. Costs were obtained from an open-access database (http://www.yaozh.com) and previous studies. The model cycle was 21 days, according to the RATIONALE-301 study, and the simulation period was patients' lifetime. Long-term direct medical costs and quality-adjusted life-years (QALYs) were determined. The incremental cost-effectiveness ratio (ICER) was used as the evaluation index. one-way sensitivity analysis (OSWA) and probabilistic sensitivity analysis (PSA) were used to analyze the uncertainty of parameters and to adjust and verify the stability of the baseline results., Results: The Tislelizumab group generated a cost of $39,746.34 and brought health benefits to 2.146 QALYs, while the cost and utility of the Sorafenib group were $26750.95 and 1.578 QALYs, respectively. The Tislelizumab group increased QALYs by 0.568, the incremental cost was $12995.39, and the ICER was $22869.64/QALY, lower than the willingness to pay threshold (WTP). OSWA results showed that the utility of progressed disease (PD), cost of Camrelizumab, and cost of Tislelizumab were the main factors affecting the ICER. PSA results showed that, within 1000 times the Monte Carlo simulation, the cost of the Tislelizumab group was lower than three times the per capita gross domestic product (GDP) of China ($37653/QALY). The cost-effectiveness acceptability curves (CEAC) revealed that when WTP was no less than $12251.00, the Tislelizumab group was the dominant scheme, and the economic advantage grew with an increasing WTP. When WTP ≥ $19000.00, the Tislelizumab group became the absolute economic advantage., Conclusion: Under the current economic conditions in China, the Tislelizumab therapeutic scheme is more cost-effective than the Sorafenib therapeutic scheme for treating patients with unresectable HCC., 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: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Anxiety disorders, common symptoms during morphine withdrawal, are important negative reinforcement factors leading to relapse. Lateral habenula serves as a negative reinforcement center, however its role in morphine withdrawal-induced anxiety remains uncovered. The hyperpolarization activated cyclic nucleotide-gated (HCN) channels have been reported to be important in emotion processing and addiction, but the role of HCN in anxiety from drug protracted abstinence remains elusive. In this study, by using behavioral test, Western blot, immunofluorescence, electrophysiology and virus-mediated regulation of HCN, we found that: (1) Intra-LHb injection of selective HCN blocker ZD7288 alleviated anxiety-like behaviors in morphine protracted abstinent male mice. (2) The LHb neuronal activity was increased by morphine protracted abstinence. (3) LHb neurons were inhibited by ZD7288 and activated by 8-Br-cAMP respectively, which were enhanced by morphine withdrawal. (4) HCN1 in the LHb was upregulated by morphine withdrawal. (5) Virus-mediated overexpression of HCN1 in the LHb was sufficient to produce anxiety-like behaviors in male mice and virus-mediated knockdown of HCN1 in the LHb prevented the anxiety-like behaviors in male mice. The findings reveal that selective blockade of HCN1 channels in the LHb may represent a therapeutic approach to morphine withdrawal-induced anxiety., Competing Interests: Declaration of competing interest All the authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The role of amyloid-β (Aβ) and tau in reversion and conversion in patients with mild cognitive impairment (MCI) remains unclear. This study aimed to investigate the influence of cerebrospinal fluid (CSF) Aβ and tau on reversion and conversion and the temporal sequence of their pathogenicity in MCI patients., Methods: 179 MCI patients were recruited from the Alzheimer's Disease Neuroimaging Initiative database and classified into two groups based on cognitive changes after follow-up: reversal group (MCI to cognitively normal) and conversion group (MCI to Alzheimer's disease). CSF biomarkers and cognitive function were measured at baseline and 2-year follow-up. Partial correlation was used to analyze the association between CSF biomarkers and cognitive function, and multivariable logistic regression to identify independent risk factors for cognitive changes at baseline and 2-year follow-up. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive ability of these risk factors for cognitive changes., Results: The differences in cognitive function and CSF biomarkers between the two groups remained consistent with baseline after 2-year follow-up. After controlling for confounding variables, there was still a correlation between CSF biomarkers and cognitive function at baseline and 2-year follow-up. Multivariable regression analysis found that at baseline, only Aβ level was independently associated with cognitive changes, while Aβ and tau were both predictive factors after 2-year follow-up. ROC curve analysis revealed that the combination of Aβ and tau [area under the curve (AUC) 0.91, sensitivity 84%, specificity 86%] in predicting cognitive changes after 2-year follow-up had better efficacy than baseline Aβ alone (AUC 0.81)., Conclusion: Aβ may precede Tau in causing cognitive changes, and the interaction between the two mediates cognitive changes in patients. This study provides new clinical evidence to support the view that Aβ pathology precedes tau pathology, which together contribute to the changes in cognitive function., 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.)

Imperata cylindrica, a medicinal plant used in Traditional Chinese Medicine, has been used to treat chronic kidney disease. Extracts of I. cylindrica display anti-inflammatory, immunomodulatory, and anti-fibrotic properties. However, the active components of the extracts and their protective mechanisms have not been fully elucidated. In this study, we explored the ability of cylindrin, the main active compound extracted from I. cylindrica, to protect against renal fibrosis and to investigate the potential mechanisms involved. At high doses, cylindrin exerted protective effects against folic acid-induced kidney fibrosis in mice. Bioinformatic analysis predicted the LXR-α/PI3K/AKT pathway as a target of regulation by cylindrin. This was supported by our in vitro and in vivo results showing that cylindrin significantly downregulated the expression of LXR-α and phosphorylated PI3K/AKT in M2 macrophages and mouse renal tissues. Furthermore, high-dose cylindrin inhibited M2 polarization of IL-4-stimulated macrophages in vitro. Our results suggest that cylindrin alleviates renal fibrosis by attenuating M2 macrophage polarization through inhibition of the PI3K/AKT pathway via downregulation of LXR-α., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Ferroptosis, a nonapoptotic form of programmed cell death characterized by significant iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various cancer-related signaling pathways. Recently, considerable progress has been made in demonstrating the critical role of lipid metabolism in regulating ferroptosis, indicating the potential of combinational strategies for treating cancer in the future. In this study, we explored the combinational effects of lipid metabolism compounds and ferroptosis inducers on renal cell carcinoma (RCC) cells. We found potent synergy of the fatty acid amide hydrolase (FAAH) inhibitor URB597 with ferroptosis inducer (1S, 3R)-RSL3 (RSL3) in inhibiting the growth and metastasis of RCC cells both in vitro and in vivo via induction of G1 cell cycle arrest and promotion of the production of lipid peroxides, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and cytosolic reactive oxygen species (ROS). In addition, inhibition of FAAH increased the sensitivity of RCC cells to ferroptosis. Genome-wide RNA sequencing indicated that the combination of URB597 and RSL3 has more significant effects on regulation of the expression of genes related to cell proliferation, the cell cycle, cell migration and invasion, and ferroptosis than either single agent alone. Moreover, we found that combinational treatment modulated the sensitivity of RCC cells to ferroptosis via the phosphatidylinositol 3 kinase (PI3K)-AKT signaling pathway. These data demonstrate that dual targeting of FAAH and ferroptosis could be a promising strategy for treating RCC., (© 2023. The Author(s).)

Objective: This study uses four COVID-19 outbreaks as examples to calculate and compare merits and demerits, as well as applicational scenarios, of three methods for calculating reproduction numbers., Method: The epidemiological characteristics of the COVID-19 outbreaks are described. Through the definition method, the next-generation matrix-based method, and the epidemic curve and serial interval ( SI )-based method, corresponding reproduction numbers were obtained and compared., Results: Reproduction numbers ( R eff ), obtained by the definition method of the four regions, are 1.20, 1.14, 1.66, and 1.12. Through the next generation matrix method, in region H R eff = 4.30, 0.44; region P R eff = 6.5, 1.39, 0; region X R eff = 6.82, 1.39, 0; and region Z R eff = 2.99, 0.65. Time-varying reproduction numbers ( R t ), which are attained by SI of onset dates, are decreasing with time. Region H reached its highest R t = 2.8 on July 29 and decreased to R t < 1 after August 4; region P reached its highest R t = 5.8 on September 9 and dropped to R t < 1 by September 14; region X had a fluctuation in the R t and R t < 1 after September 22; R t in region Z reached a maximum of 1.8 on September 15 and decreased continuously to R t < 1 on September 19., Conclusion: The reproduction number obtained by the definition method is optimal in the early stage of epidemics with a small number of cases that have clear transmission chains to predict the trend of epidemics accurately. The effective reproduction number R eff , calculated by the next generation matrix, could assess the scale of the epidemic and be used to evaluate the effectiveness of prevention and control measures used in epidemics with a large number of cases. Time-varying reproduction number R t , obtained via epidemic curve and SI , can give a clear picture of the change in transmissibility over time, but the conditions of use are more rigorous, requiring a greater sample size and clear transmission chains to perform the calculation. The rational use of the three methods for reproduction numbers plays a role in the further study of the transmissibility of COVID-19., 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 Abudunaibi, Liu, Guo, Zhao, Rui, Song, Wang, Chen, Frutos, Su and Chen.)

Objectives: Aging is a process that involves comprehensive physiological changes throughout the body, and improvements in the exercise capacity of individuals may delay aging and relieve fatigue. Probiotics are subject to ongoing research to investigate their antioxidant properties. The purpose of this study was to investigate the effect of the probiotic Lactobacillus plantarum KSFY01 ( L. plantarum KSFY01) on exercise tolerance in mice induced into a state of accelerated physiological aging by oxidative stress., Methods: A mouse model of accelerated aging was established using D-galactose to induce oxidative stress. The bacteria L. plantarum KSFY01 was isolated from fermented yak yogurt. The effect of L. plantarum KSFY01 on the improvement of exercise capacity in aging-accelerated mice was evaluated by measuring their running time until exhaustion, histopathological sections, related biochemical indicators, and underlying gene expression., Results: The oral administration of L. plantarum KSFY01 prolonged the running time of mice and reduced their creatine kinase (CK), alanine aminotransferase (ALT), and aspartate aminotransferasem (AST) levels. From this study, we observed that L. plantarum KSFY01 significantly improved the exercise capacity of mice and alleviated liver damage. Treatment with L. plantarum KSFY01 reduced the blood urea nitrogen (BUN), lactic acid (LD) accumulation, and lactate dehydrogenase (LDH) elevations produced by the accelerated aging state, and also reversed the changes in muscle glycogen (MG). Overall, L. plantarum KSFY01 could effectively improve metabolite accumulation, thereby relieving fatigue in exercised mice. The results of the antioxidant indices in vivo showed that L. plantarum KSFY01 intervention increased the activity of antioxidant enzymes, decreased the level of malondialdehyde (MDA), and restored the balance between the oxidative and antioxidant systems in fatigued mice. By investigating the underlying molecular mechanism, our results showed that L. plantarum KSFY01 intervention significantly reversed the decline in the expression levels of nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway-related factors and improved the body's antioxidant capacity. We determined that the underlying molecular mechanism responsible for the antioxidant effect of L. plantarum KSFY01 mainly involves the activation of the Nrf2 pathway. The effect of L. plantarum KSFY01 was dose-dependent, and the expression level of Nrf2 increased with increasing dosage of the probiotic., Conclusion: This study demonstrated that the probiotic L. plantarum KSFY01 exerts antioxidant effects and improved the athletic ability of mice. These findings are of significance to the development and utilization of probiotic resources., 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 © 2022 Chen, Liu, Zhang, Wang and Li.)

Background: Recently, despite the steady decline in the tuberculosis (TB) epidemic globally, school TB outbreaks have been frequently reported in China. This study aimed to quantify the transmissibility of Mycobacterium tuberculosis (MTB) among students and non-students using a mathematical model to determine characteristics of TB transmission., Methods: We constructed a dataset of reported TB cases from four regions (Jilin Province, Xiamen City, Chuxiong Prefecture, and Wuhan City) in China from 2005 to 2019. We classified the population and the reported cases under student and non-student groups, and developed two mathematical models [nonseasonal model (Model A) and seasonal model (Model B)] based on the natural history and transmission features of TB. The effective reproduction number (R eff ) of TB between groups were calculated using the collected data., Results: During the study period, data on 456,423 TB cases were collected from four regions: students accounted for 6.1% of cases. The goodness-of-fit analysis showed that Model A had a better fitting effect (P < 0.001). The average R eff of TB estimated from Model A was 1.68 [interquartile range (IQR): 1.20-1.96] in Chuxiong Prefecture, 1.67 (IQR: 1.40-1.93) in Xiamen City, 1.75 (IQR: 1.37-2.02) in Jilin Province, and 1.79 (IQR: 1.56-2.02) in Wuhan City. The average R eff of TB in the non-student population was 23.30 times (1.65/0.07) higher than that in the student population., Conclusions: The transmissibility of MTB remains high in the non-student population of the areas studied, which is still dominant in the spread of TB. TB transmissibility from the non-student-to-student-population had a strong influence on students. Specific interventions, such as TB screening, should be applied rigorously to control and to prevent TB transmission among students., (© 2022. The Author(s).)

In recent years, hotels have occasionally engaged in unethical behaviour. This has become an urgent problem that requires a solution. Based on social exchange theory, this study constructs a theoretical model of the relationship between hospitality's ethical values and unethical behaviour. According to 543 questionnaires, the findings indicate that hospitality's ethical values negatively affect the unethical behaviour of employees. Work values played a part in the intermediary role between the two, and perceived organisational support significantly positively moderated the relationship between hospitality's ethical values and unethical behaviour. By exploring the logical relationship between hotels' and employees' morality, this study expands the research content and theoretical framework of unethical employee behaviour and helps to bridge the work values of hotels and individuals. Furthermore, it helps to build a good hotel ethical value system, which can effectively reduce and suppress the emergence of unethical employee behaviour., 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 © 2022 Chen and Liu.)

Aim of the Study: Although vine tea has demonstrated broad-spectrum anti-cancer properties, its main active compounds, dihydromyricetin (DMY) and myricitrin (MYT), exert weaker effects than the tea extracts. This study aimed to investigate the synergistic inhibitory effects of DMY and MYT on B16F10 cell proliferation and their synergistic inhibitory effects., Methods: The effect of vine tea extracts (VTEs) and their active compounds on B16F10 cells was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, fluorescence staining, and flow cytometry. The synergistic effects were calculated by the combination index (CI), and its mechanism was discussed by network pharmacology., Results: Different VTEs varied in their inhibition of B16F10 cell growth, with IC 50 values ranging from 4.45 to 12.95 μg/mL, Among these, Guangzhou Qingyuan (Level 2), appeared to have the most potent inhibitory effect. The IC 50 value of mix-use of DMY and MYT was 19.94∼64.4 μM, of which DMY: MYT = 8:1 had the minimum IC 50 value of 19.94 μM. Combinations in the 1:1∼8:1 range had stronger effects than the isolated active compound. When they were mixed at the ratio of 1:4∼8:1, CI < 1, showing a synergistic effect. The combination of DMY and MYT also significantly inhibited the tyrosinase activity in B16F10 cells, consistent with its impact on cell proliferation. The eight potential targets were identified by network pharmacology regulating melanin metabolism, tyrosine metabolism, and melanogenesis signaling. According to the analysis of protein-protein interactions, TP53 , TNF , and TYR might be critical targets for preventing and treating melanoma., Conclusion: We found that DMY and MYT induced apoptosis of B16F10 cells, and their combined application had a significant synergistic effect. The present findings indicated that vine tea had a multi-pathway and multi-target impact on the prevention and treatment of melanoma., 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 © 2022 Zhao, Kong, Liu, Shi, Qi and Chen.)

Objective: To analyze the effects of metoprolol (MET) plus atorvastatin (ATO) on carotid intima-media thickness (IMT) and homocysteine (Hcy) level in carotid atherosclerosis (CAS) patients., Methods: In this retrospective study, 90 patients with CAS admitted to the Hangzhou Ninth People's Hospital between January 2019 and July 2021 were enrolled, including 40 cases (control group, the Con) treated with MET and 50 cases treated with the combination therapy of MET plus ATO (Research group, the Res). The efficacy and related influencing factors were observed and compared. The clinical effects (IMT, plaque score), Hcy level, inflammatory cytokines (ICs; matrix metalloproteinase-9 [MMP-9], high-sensitivity C-reactive protein [hs-CRP]), blood lipid indices (low-/high- density lipoprotein cholesterol [LDL-C/HDL-C], total cholesterol [TC], triglyceride [TG]) and coagulation markers (thrombin time [TT], prothrombin time [PT], activated partial thromboplastin time [APTT], fibrinogen [FIB]) of the two groups were observed and compared., Results: The results identified a statistically higher overall response rate in the Res group. Age, coronary heart disease, cerebral infarction and plaque score were confirmed to be closely related to the efficacy of CAS. In addition, statistically lower post-treatment IMT, plaque score, MMP-9, hs-CRP, LDL-C, TG, TC and FIB while higher PT, TT and APTT were determined in the Res group compared with the pre-treatment values and the Con group., Conclusions: MET plus ATO can significantly improve efficacy, reduce IMT and plaque score of patients with CAS, as well as improve inflammatory factors, blood lipid indices and coagulation markers, for which it deserves clinical promotion., Competing Interests: None., (AJTR Copyright © 2022.)

Background: Meteorological factors have been proven to affect pathogens; both the transmission routes and other intermediate. Many studies have worked on assessing how those meteorological factors would influence the transmissibility of COVID-19. In this study, we used generalized estimating equations to evaluate the impact of meteorological factors on Coronavirus disease 2019 (COVID-19) by using three outcome variables, which are transmissibility, incidence rate, and the number of reported cases., Methods: In this study, the data on the daily number of new cases and deaths of COVID-19 in 30 provinces and cities nationwide were obtained from the provincial and municipal health committees, while the data from 682 conventional weather stations in the selected provinces and cities were obtained from the website of the China Meteorological Administration. We built a Susceptible-Exposed-Symptomatic-Asymptomatic-Recovered/Removed (SEIAR) model to fit the data, then we calculated the transmissibility of COVID-19 using an indicator of the effective reproduction number ( R eff ). To quantify the different impacts of meteorological factors on several outcome variables including transmissibility, incidence rate, and the number of reported cases of COVID-19, we collected panel data and used generalized estimating equations. We also explored whether there is a lag effect and the different times of meteorological factors on the three outcome variables., Results: Precipitation and wind speed had a negative effect on transmissibility, incidence rate, and the number of reported cases, while humidity had a positive effect on them. The higher the temperature, the lower the transmissibility. The temperature had a lag effect on the incidence rate, while the remaining five meteorological factors had immediate and lag effects on the incidence rate and the number of reported cases., Conclusion: Meteorological factors had similar effects on incidence rate and number of reported cases, but different effects on transmissibility. Temperature, relative humidity, precipitation, sunshine hours, and wind speed had immediate and lag effects on transmissibility, but with different lag times. An increase in temperature may first cause a decrease in virus transmissibility and then lead to a decrease in incidence rate. Also, the mechanism of the role of meteorological factors in the process of transmissibility to incidence rate needs to be further explored., 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 © 2022 Lin, Rui, Xie, Zhan, Chen, Zhao, Zhu, Li, Deng, Yu, Li, Ke, Zeng, Su, Chiang and Chen.)

Objective: In China, the burden of shigellosis is unevenly distributed, notably across various ages and geographical areas. Shigellosis temporal trends appear to be seasonal. We should clarify seasonal warnings and regional transmission patterns., Method: This study adopted a Logistic model to assess the seasonality and a dynamics model to compare the transmission in different areas. The next-generation matrix was used to calculate the effective reproduction number ( R eff ) to quantify the transmissibility., Results: In China, the rate of shigellosis fell from 35.12 cases per 100,000 people in 2005 to 7.85 cases per 100,000 people in 2017, peaking in June and August. After simulation by the Logistic model, the 'peak time' is mainly concentrated from mid-June to mid-July. China's 'early warning time' is primarily focused on from April to May. We predict the 'peak time' of shigellosis is the 6.30th month and the 'early warning time' is 3.87th month in 2021. According to the dynamics model results, the water/food transfer pathway has been mostly blocked off. The transmissibility of different regions varies greatly, such as the mean R eff of Longde County (3.76) is higher than Xiamen City (3.15), higher than Chuxiong City (2.52), and higher than Yichang City (1.70)., Conclusion: The 'early warning time' for shigellosis in China is from April to May every year, and it may continue to advance in the future, such as the early warning time in 2021 is in mid-March. Furthermore, we should focus on preventing and controlling the person-to-person route of shigellosis and stratified deploy prevention and control measures according to the regional transmission., 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., (© 2022 The Authors.)

In this study, we have evaluated and examined various nursing effects of improved administration of protamine sulfate neutralizing heparin after cardiopulmonary bypass. For this purpose, retrospective analysis was made about the nursing records and clinical data of 216 patients who underwent cardiac operation under cardiopulmonary bypass in our hospital from January 2018 to December 2020. Among the enrolled patients, 118 patients were given subinterval administration of protamine sulfate neutralizing heparin via aortic root with the assistance of the scrub nurse at the end of cardiac surgery (improved group). A total of 98 patients were administered by the circulating nurse via the central vein (regular group). The changes of body temperature, blood pressure, oxygen saturation before and after heparin neutralization, and the total volume of thoracic drainage within 24 hours after operation were observed in the two groups, so as to evaluate the application effect of the improved administration of protamine sulfate neutralizing heparin from the perspective of nursing. There was no significant difference in age, gender, and other basic characteristics between the two groups ( P > 0.05). The volume of drainage in the improved group and the regular group within 24 hours after surgery was 234 ± 26.3 ml and 307 ± 31.8 ml, respectively, P < 0.01, and the difference was statistically significant. The incidence of adverse reactions in the improved group was much lower than that in the regular group, P < 0.01. The administration route of the improved group was beneficial to maintain the stability of hemodynamics when using the protamine sulfate to neutralize heparin, which is worthy of clinical nursing promotion., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Jia Hu et al.)

Introduction: Modeling on infectious diseases is significant to facilitate public health policymaking. There are two main mathematical methods that can be used for the simulation of the epidemic and prediction of optimal early warning timing: the logistic differential equation (LDE) model and the more complex generalized logistic differential equation (GLDE) model. This study aimed to compare and analyze these two models., Methods: We collected data on (coronavirus disease 2019) COVID-19 and four other infectious diseases and classified the data into four categories: different transmission routes, different epidemic intensities, different time scales, and different regions, using R 2 to compare and analyze the goodness-of-fit of LDE and GLDE models., Results: Both models fitted the epidemic curves well, and all results were statistically significant. The R 2 test value of COVID-19 was 0.924 ( p < 0.001) fitted by the GLDE model and 0.916 ( p < 0.001) fitted by the LDE model. The R 2 test value varied between 0.793 and 0.966 fitted by the GLDE model and varied between 0.594 and 0.922 fitted by the LDE model for diseases with different transmission routes. The R 2 test values varied between 0.853 and 0.939 fitted by the GLDE model and varied from 0.687 to 0.769 fitted by the LDE model for diseases with different prevalence intensities. The R 2 test value varied between 0.706 and 0.917 fitted by the GLDE model and varied between 0.410 and 0.898 fitted by the LDE model for diseases with different time scales. The GLDE model also performed better with nation-level data with the R 2 test values between 0.897 and 0.970 vs. 0.731 and 0.953 that fitted by the LDE model. Both models could characterize the patterns of the epidemics well and calculate the acceleration weeks., Conclusion: The GLDE model provides more accurate goodness-of-fit to the data than the LDE model. The GLDE model is able to handle asymmetric data by introducing shape parameters that allow it to fit data with various distributions. The LDE model provides an earlier epidemic acceleration week than the GLDE model. We conclude that the GLDE model is more advantageous in asymmetric infectious disease data simulation., 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 © 2022 Li, Lin, Rui, Bai, Deng, Chen, Zhu, Luo, Yu, Liu, Zhang, Su, Zhao, Zhang, Chiang, Liu, Luo and Chen.)

Background: In this study, we aimed to quantify the contribution of different transmission routes of the Middle East respiratory syndrome (MERS) and determine its transmissibility., Methods: Based on the natural history and transmission features of MERS in different countries, a susceptible-exposed-symptomatic-asymptomatic-recovered/death (SEIARD) model and a multi-route dynamic model (MMDM). The SEIARD model and MMDM were adopted to simulate MERS in South Korea and Saudi Arabia, respectively. Data on reported MERS cases in the two countries were obtained from the World Health Organization. Thereafter, the next generation matrix method was employed to derive the equation for the basic reproduction number (R 0 ), and the model fitting procedure was adopted to calculate the R 0 values corresponding to these different countries., Results: In South Korea, 'Person-to-Person' transmission was identified as the main mode of MERS transmission in healthcare settings, while in Saudi Arabia, in addition to 'Person-to-Person' transmission, 'Host-to-Host' and 'Host-to-Person' transmission also occurred under certain scenarios, with camels being the main host. Further, the fitting results showed that the SEIARD model and MMDM fitted the data well. The mean R 0 value was 8.59 (95% confidence interval [CI]: 0-28.02) for MERS in South Korea, and for MERS in Saudi Arabia, it was 1.15 and 1.02 (95% CI: 0.86-1.44) for the 'Person-to-Person' and 'Camel-to-Camel' transmission routes, respectively., Conclusions: The SEIARD and MMDM model can be used to simulate the transmission of MERS in different countries. Additionally, in Saudi Arabia, the transmissibility of MERS was almost the same among hosts (camels) and humans., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Human immunodeficiency virus (HIV) is a single-stranded RNA virus that can weaken the body's cellular and humoral immunity and is a serious disease without specific drug management and vaccine. This study aimed to evaluate the epidemiologic characteristics and transmissibility of HIV. Methods: Data on HIV follow-up were collected in Nanning City, Guangxi Zhuang Autonomous, China. An HIV transmission dynamics model was built to simulate the transmission of HIV and estimate its transmissibility by comparing the effective reproduction number ( R eff ) at different stages: the rapid growth period from January 2001 to March 2005, slow growth period from April 2005 to April 2011, and the plateau from May 2011 to December 2019 of HIV in Nanning City. Results: High-risk areas of HIV prevalence in Nanning City were mainly concentrated in suburbs. Furthermore, high-risk groups were those of older age, with lower income, and lower education levels. The R eff in each stage (rapid growth, slow growth, and plateau) were 2.74, 1.62, and 1.15, respectively, which suggests the transmissibility of HIV in Nanning City has declined and prevention and control measures have achieved significant results. Conclusion: Over the past 20 years, the HIV incidence in Nanning has remained at a relatively high level, but its development trend has been curbed. Transmissibility was reduced from 2.74 to 1.15. Therefore, the prevention and treatment measures in Nanning City have achieved significant improvement., 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 Lin, Deng, Rui, Guo, Hu, Chen, Tang, Zhou, Zhao, Lin, Zhu, Yang, Wang, Xu, Liu, Yang, Li, Li, Luo, Liu, Liu, Huang, Yao, Nong, Nong, Wu, Luo, Chen, Frutos, Yang, Li, Cui and Chen.)

Yak yogurt is mainly produced in Qinghai-Tibet Plateau. It is a kind of naturally fermented dairy product. It contains abundant microorganisms. Lactobacillus fermentum (LF) HFY03 is a lactic acid bacteria derived from it. Our main research content is to study the influence of LF-HFY03 on the antifatigue and antioxidation ability of running exhausted mice. We gave different doses of LF-HFY03 to mice by gavage for 4 weeks. We selected vitamin C as the positive control group, mainly to study the relationship between antioxidant capacity and fatigue resistance and LF-HFY03 in mice with running exhaustion. The results showed that LF-HFY03 and vitamin C could significantly improve the running time of mice. And with the increase in LF-HFY03 concentration, the exhaustion time of mice was also extended. LF-HFY03 can reduce the content of urea nitrogen and lactic acid and also can increase the content of free fatty acids and liver glycogen. The levels of alanine aminotransferase, serum creatine kinase, and aspartate aminotransferase in mice decreased gradually as the antioxidant peptide level of walnut albumin increased. LF-HFY03 can reduce malondialdehyde (MDA) levels in a quantification-dependent manner and can also increase catalase (CAT) and superoxide dismutase (SOD) levels. LF-HFY03 can also increase the expressions of CAT mRNA, Cu/Zn-SOD, and Mn-SOD in the liver of mice. At the same time, LF-HFY03 can also increase the expression of protein of threonine transporter 1 (AST1)/alanine/cysteine/serine, mRNA, nNOS, and eNOS. At the same time, the solution could reduce the expression of TNF- α , syncytin-1, and inducible nitric oxide synthase (iNOS). The results showed that LF-HFY03 has a high development and application prospect as an antifatigue probiotic nutritional supplement., Competing Interests: All authors declare that they have no competing interests., (Copyright © 2021 Junxiao Zhang et al.)

Bone metastasis is one of the leading causes of cancer-related death and remains incurable in spite of great efforts. Bone-targeted nanoparticle-based drug carriers can overcome the difficulties in delivering therapeutic agents to metastatic bone and endowing them with a stimuli-responsive feature for controllable drug release can further maximize their therapeutic outcome. In light of hypoxic microenvironment of bone metastasis, we herein reported a bone-targeted and hypoxia-responsive polymeric micelle system for effective treatment of bone metastatic prostate cancer. The micelles were self-assembled from a polyethylene glycol and poly-l-lysine based copolymer using alendronate as a bone-targeted moiety and azobenzene as a hypoxia-responsive linker, showing a high affinity to metastatic bone and a high sensitivity in responding to hypoxia in vitro. In vivo studies further showed that after a selective accumulation in metastatic bone, the micelles could respond to hypoxic bone metastasis for rapid drug release to an effective therapeutic dosage. As a result, the micelles could suppress tumor growth in bone and inhibit bone destruction by inhibiting osteoclast activity and promoting osteoblast activity, achieving an enhanced therapeutic outcome with relieved bone pain and prolonged survival time. Bone-targeted and hypoxia-responsive nanocarriers therefore represent a promising advancement for treating bone metastasis. To our best knowledge, it might be the first example of the application of hypoxia-responsive nanocarriers in treating bone metastasis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Chinese Sichuan pickle is a fermented food rich in microorganisms. Microorganisms have the potential to become an important new form of potent future therapeutic capable of treating human disease. Selecting vitamin C as a positive control, a lactic acid bacteria ( Lactobacillus plantarum CQPC02, LP-CQPC02) isolated from Sichuan pickle was given to mice over 4 weeks to investigate the effect of CQPC02 on fatigue levels and biochemical oxidation phenomena in exercise-exhausted Institute of Cancer Research (ICR) mice. The fatigue model was established by forced swimming of mice, the levels of hepatic glycogen, skeletal muscle glycogen, lactic acid, blood urea nitrogen and free fatty acid were measured by physicochemical methods, serum serum creatine kinase (CK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels were measured by kits, the histopathological changes in the livers of mice were observed by H&E slicing, and the mRNA changes in the livers and skeletal muscles were observed by quantitative polymerase chain reaction (qPCR). Both vitamin C and LP-CQPC02 increased swimming exhaustion time. The concentration of LP-CQPC02 and exhaustion time were positively correlated. LP-CQPC02 also increased liver glycogen, skeletal muscle glycogen and free fatty acid content in mice and reduced lactic acid and blood urea nitrogen content in a dose-dependent manner. As walnut albumin antioxidant peptide concentration increased, levels of mouse CK, AST, and AST gradually decreased. LP-CQPC02 increased SOD and CAT levels and decreased MDA levels in a dose-dependent fashion. LP-CQPC02 up-regulated expression of mRNA encoding copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and CAT in swimming exhaustion mouse liver tissue. LP-CQPC02 also up-regulated alanine/serine/cysteine/threonine transporter 1 (ASCT1) expression while down-regulating syncytin-1, inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) expression in swimming exhaustion mouse skeletal muscle. Overall, LP-CQPC02 had a clear anti-fatigue and anti-oxidation effect. This suggests that LP-CQPC02 can be developed as a microbiological therapeutic agent., 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 Yi, Feng, Chen, Long, Park and Zhao.)

Background: Hand, foot, and mouth disease (HFMD) is a global infectious disease; particularly, it has a high disease burden in China. This study was aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics, and to calculate the early warning signals of HFMD by using a logistic differential equation (LDE) model., Methods: This study included datasets of HFMD cases reported in seven regions in Mainland China. The early warning time (week) was calculated using the LDE model with the key parameters estimated by fitting with the data. Two key time points, "epidemic acceleration week (EAW)" and "recommended warning week (RWW)", were calculated to show the early warning time., Results: The mean annual incidence of HFMD cases per 100,000 per year was 218, 360, 223, 124, and 359 in Hunan Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County across the southern regions, respectively and 60 and 34 in Jilin Province and Longde County across the northern regions, respectively. The LDE model fitted well with the reported data (R2 > 0.65, P < 0.001). Distinct temporal patterns were found across geographical regions: two early warning signals emerged in spring and autumn every year across southern regions while one early warning signals in summer every year across northern regions., Conclusions: The disease burden of HFMD in China is still high, with more cases occurring in the southern regions. The early warning of HFMD across the seven regions is heterogeneous. In the northern regions, it has a high incidence during summer and peaks in June every year; in the southern regions, it has two waves every year with the first wave during spring spreading faster than the second wave during autumn. Our findings can help predict and prepare for active periods of HFMD., Competing Interests: The authors have declared that no competing interests exist.

Stroke is a cerebrovascular disease that results in decreased blood flow. Although Panax notoginseng (PN), a Chinese herbal medicine, has been proven to promote stroke recovery, its molecular mechanism remains unclear. In this study, middle cerebral artery occlusion (MCAO) was induced in rats with thrombi generated by thread and subsequently treated with PN. After that, staining with 2,3,5-triphenyltetrazolium chloride was employed to evaluate the infarcted area, and electron microscopy was used to assess ultrastructural changes of the neurovascular unit. RNA-Seq was performed to determine the differential expressed genes (DEGs) which were then verified by qPCR. In total, 817 DEGs were identified to be related to the therapeutic effect of PN on stroke recovery. Further analysis by Gene Oncology analysis and Kyoto Encyclopedia of Genes and Genomes revealed that most of these genes were involved in the biological function of nerves and blood vessels through the regulation of neuroactive live receptor interactions of PI3K-Akt, Rap1, cAMP, and cGMP-PKG signaling, which included in the 18 pathways identified in our research, of which, 9 were reported firstly that related to PN's neuroprotective effect. This research sheds light on the potential molecular mechanisms underlying the effects of PN on stroke recovery., Competing Interests: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2020 Lanqing Meng et al.)

Stimuli-responsive drug delivery systems using endogenous stimuli from tumor microenvironments such as acidic pH, over-expressed enzyme, and high redox potential as triggers have shown tremendous promise in cancer therapy. However, their clinical application is severely limited because of tumor heterogeneity. Hypoxia, a physiological feature observed in almost all solid tumors and even in nodules with very small size, has currently emerged as a more general but efficient stimulus to trigger release. Herein, we developed hypoxia-responsive hybrid liposomes (HR-HLPs), composed of azo-inserted organokoxysilane-based lipid analogue as a responsive component and commercial phospholipid for reducing the rigidity of liposomal membrane caused by azo, for drug delivery targeting tumor hypoxia. HR-HLPs had the advantages of high structural stability to avoid premature drug leakage when circulating in the blood and high sensitivity in responding to hypoxia once reaching tumor sites. HR-HLPs exhibit deep tumor penetration capability, enabling effective delivery to hypoxic regions distant from tumor vessels. Moreover, HR-HLPs could selectively release their payload, co-localizing with over-expressed hypoxia inducible factor 1α (HIF-1α) in vitro and in vivo. As a result, HR-HLPs showed improved therapeutic outcome accompanied by reduced adverse effects. The results highlighted the potential application of azo-inserted responsive hybrid liposomes for hypoxia-targeted drug delivery. STATEMENT OF SIGNIFICANCE., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The transmission features and the feasibility of containing shigellosis remain unclear among a population-based study in China., Methods: A population-based Susceptible - Exposed - Infectious / Asymptomatic - Recovered (SEIAR) model was built including decreasing the infectious period (DIP) or isolation of shigellosis cases. We analyzed the distribution of the reported shigellosis cases in Hubei Province, China from January 2005 to December 2017, and divided the time series into several stages according to the heterogeneity of reported incidence during the period. In each stage, an epidemic season was selected for the modelling and assessing the effectiveness of DIP and case isolation., Results: A total of 130,770 shigellosis cases were reported in Hubei Province. The median of R eff was 1.13 (range: 0.86-1.21), 1.10 (range: 0.91-1.13), 1.09 (range: 0.92-1.92), and 1.03 (range: 0.94-1.22) in 2005-2006 season, 2010-2011 season, 2013-2014 season, and 2016-2017 season, respectively. The reported incidence decreased significantly (trend χ 2  = 8260.41, P <  0.001) among four stages. The incidence of shigellosis decreased sharply when DIP implemented in three scenarios (γ = 0.1, 0.1429, 0.3333) and when proportion of case isolation increased., Conclusions: Year heterogeneity of reported shigellosis incidence exists in Hubei Province. It is feasible to contain the transmission by implementing DIP and case isolation.

Purpose: β-elemene and cisplatin combined chemotherapy currently is one of the most important settings available for lung cancer therapy in China. However, the clinical outcome is limited by their pharmacokinetic drawbacks. On the other hand, most of nanomedicines have failed in clinical development due to the huge differences between heterogeneous clinical tumor tissues and homogenous cell-derived xenografts. In this work, we fabricated a β-elemene and cisplatin co-loaded liposomal system to effectively treat lung cancer., Method: In vitro cytotoxicity of co-loaded liposomes was studied by MTT, trypan and Hoechst/PI staining, and western blot in A549, A549/DDP, and LCC cells. In vivo antitumor efficacy was evaluated in cell-derived and clinically relevant patient-derived xenografts., Results: Co-loaded liposomes were more cytotoxic to cancer cells, especially than the combination of single-loaded liposomes, benefiting from their simultaneous drug internalization and release. As a result, they exhibited desirable therapeutic outcome in both cell-derived and patient-derived xenografts., Conclusion: β-elemene and cisplatin co-loaded liposomes are a clinically promising candidate for effective lung cancer therapy.

Inflammatory cytokines and chemokines play essential roles in the occurrence and persistence of neuropathic pain (NP). Chronic constriction injury (CCI) enhances the activation of p-ERK, which is involved in neuropathic pain. Although the chemokine CXCL10 and its receptor CXCR3 are implicated in the pathophysiology of itch, it is largely unexplored for neuropathic pain. In this study, we determined the role of the CXCL10-CXCR3 axis in NP using a well-established CCI model. CCI significantly induced mechanical allodynia and thermal hyperalgesia. Following the pain course, a significant increase of CXCL10 and CXCR3 in both dorsal root ganglion (DRG) neurons and spinal cord (SC) neurons was detected in rats. Furthermore, intrathecal injection of CXCR3 inhibitor AMG487 was found to attenuate pain hypersensitivity in a dose-dependent manner in CCI. The expression of p-ERK was also depressed after intrathecal injection of AMG487 associated with a significant laxation of hyperalgesia, which demonstrated that the interaction of CXCL10/CXCR3 possibly took part in neuropathic pain by regulating p-ERK signaling in the SC. Overall, these findings demonstrate that the CXCL10/CXCR3 signaling pathway is critical in CCI., (Copyright © 2018. Published by Elsevier B.V.)

OBJECTIVE To develop a new method for detecting 22q11.2 deletion syndrome (22q11.2 DS) in clinical settings. METHODS Specific primers and fluorescence probes were designed to target the TBX1 gene within the 22q11.2 deletion region and a reference gene RPP30. Multiplexed droplet digital PCR (ddPCR) was run to detect the 22q11.2 microdeletion by calculating the ratio of positive droplet number of TBX1/RPP30. RESULTS Three cases of 22q11.2 microdeletion previously confirmed by array comparative genome hybridization were successfully identified. Subsequently, the ddPCR detected two further cases of 22q11.2 microdeletion among 14 children with congenital heart diseases. CONCLUSION The ddPCR technique has provided a rapid and cost-effective method for detecting 22q11.2 microdeletion in clinical settings.

To study the role of microRNA (miR) in the lactation physiology of water buffalo, 2 multiparous dairy buffaloes (including an 8-yr-old buffalo that had been lactating for 3 mo, as well as a 10-yr-old nonlactating, nonpregnant buffalo) were used for miR library construction. The profile of differentially expressed miR in lactating and nonlactating mammary gland tissues of these water buffalo were investigated using Illumina-Solexa high-throughput sequencing technology (Illumina, San Diego, CA). The data identified 259 miR families, 359 mature miR, 363 pre-miR, 230 novel buffalo miR, and 5 buffalo-specific miR that were expressed in mammary tissues. Some highly significantly differentially expressed miR were explored, including bbu-miR-497, bbu-miR-30a-5p, bbu-miR-148a, bbu-miR-29a, bbu-miR-125a, bbu-miR-125b, and bbu-miR-103. The expression patterns of 18 miR were confirmed by quantitative real-time PCR in both tissues, and the expression of bbu miR-103 and novel miR-57 constituted the largest differences between lactating and nonlactating tissues. Further functional analysis indicated that the overexpression or suppression of miR-103 in buffalo mammary epithelial cells downregulated or upregulated the expression of pantothenate kinase 3, and also significantly increased the transcription factor steroid regulatory element binding protein, followed by the acceleration of de novo synthesis of fatty acids by upregulation of acetyl coenzyme A carboxylase α expression. The expression levels of 34 predicted target genes of novel-miR-57 in lactating and nonlactating mammary gland tissues were all analyzed by quantitative real-time PCR. Finally, only the expression of docking protein 4 could be upregulated or downregulated selectively by bbu-novel-miR-57 in buffalo mammary epithelial cells and the Bcap-37 cell line. This study provides an overview of the miR expression profile of water buffalo and the interaction between some key miR and their target genes, which may improve understanding of the important roles of miR in buffalo milk fat synthesis., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Recent studies have demonstrated that diabetes impairs the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway, while insulin resistance syndrome has been associated with alterations of this pathway in diabetic rats after ischemia/reperfusion (I/R), and activation of C-jun N-terminal kinase (JNK) is involved. The present study was designed to investigate whether inhibiting JNK activity would partially restore the PI3K/Akt signaling pathway and protect against myocardial I/R injury in diabetic rats, and to explore the effect of intervention with salvianolic acid A (Sal A). The inhibitor of JNK (SP600125) and Sal A were used in type 2 diabetic (T2D) rats, outcome measures included heart hemodynamic data, myocardial infarct size, the release of lactate dehydrogenase (LDH), SERCA2a activity, cardiomyocyte apotosis, expression levels of Bcl-2, Bax and cleaved caspase-3, and the phosphorylation status of Akt and JNK. The p-Akt levels were increased after myocardial I/R in non-diabetic rats, while there was no change in diabetic rats. Pretreatment with the SP600125 and Sal A decreased the p-JNK levels and increased the p-Akt levels in diabetic rats with I/R, and heart hemodynamic data improved, infarct size and LDH release decreased, SERCA2a activity increased, Bax and cleaved caspase-3 expression levels decreased, and the expression of Bcl-2 and the Bcl-2/Bax ratio increased. Our results suggest that the JNK/PI3K/Akt signaling pathway is involved in myocardial I/R injury in diabetic rats and Sal A exerts an anti-apoptotic effect and improves cardiac function following I/R injury through the JNK/PI3K/Akt signaling pathway in this model.

Deregulation of phenotypic modulation in VSMCs is the initial stage of atherosclerosis, especially in diabetes. Functional deficiency of IRAK4 inhibits the formation of vascular lesions in ApoE-/- mice. Therefore, in this study, we examined the functions of IRAK4 in the regulation of VSMCs differentiation and phenotypic modulation at the levels of transcription and translation in T2D rats. The T2D rat model was generated by feeding a high-fat diet and injecting a low dose of streptozotocin intraperitoneally. VSMCs were isolated from the thoracic aortas of the T2D rats. VSMCs proliferation and migration were measured using water soluble tetrazolium salt-1 assay, 5-ethynyl-29-deoxyuridine staining and migration assay. IRAK4 was knocked down by siRNA and inhibited by an IRAK1/4 inhibitor. The mRNAs and proteins of signal molecules and phenotypic markers were detected by qRT-PCR and western blotting. The results demonstrated that LPS significantly increased viability, cell migration rate and amount of DNA in VSMCs. The IRAK4 inhibitor also reduced LPS-mediated protein expression of myosin heavy chain and nuclear factor κB p65 subunit and increased smooth muscle 22α expression. Moreover, IRAK4 knock-down reduced the LPS-mediated expression of mRNAs for myosin heavy chain, nuclear factor κB p65 subunit, and monocyte chemoattractant protein-1 (MCP-1), but increased the mRNA of smooth muscle 22α in VSMCs. The activation of IRAK4 phenotypically modulated VSMCs from differentiation to dedifferentiation. Inactivation of IRAK4 exerts a protective effect on VSMCs differentiation and inhibits inflammation. IRAK4 could therefore be a target for interventions to prevent and treat the initial phase of atherosclerosis.