Search

Background: Abusive head trauma (AHT) is a serious health problem that results the highest mortality among children who are maltreated. Many AHT survivors suffer from long-term sequelae and require medical treatment. However, the knowledge of AHT-attributable health services utilization and costs at national level are limited., Objective: To estimate health services utilization and costs attributable to AHT among children aged 0-4 years in Taiwan., Participants and Setting: Sixty-three fatal and 664 survival AHT cases were identified using Taiwan national population database between 2003 and 2015. A total of 2656 non-AHT children were exactly 4:1 matched to the survival cases based on their birth year, gender, the calendar year of the index date, insured location, and health insurance premium (social economic status indicator)., Methods: Health services utilization and costs were calculated on an annual basis for 3 years after the index date. AHT-attributable health services utilization and costs during 3-year follow-up period was evaluated by regression models., Results: AHT diagnosis was positively associated with inpatient admissions, length of stay, emergency room (ER) visits, and outpatient visits. AHT-attributable medical costs were 1.64-17.27 times, 1.25-5.22 times, and 1.77-2.36 times greater for inpatient, ER, and outpatient during 3-year period than matched controls, respectively. Fatal AHT cases had higher inpatient utilization and greater medical costs than AHT survivors., Conclusions: Children with AHT had greater health services utilization and higher costs for years. Strategies to reduce the burden of AHT on health care system are imperative., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This meta-analysis compared the outcomes of transradial access (TRA) and transfemoral access (TFA) in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in recent decades. We searched multiple databases for articles published between January 1, 2015, and December 31, 2020. Six observational studies with 11,736 patients were analyzed. Data included baseline demographics, Japan-chronic total occlusion (J-CTO) score, sheath size, PCI vessel, retrograde method, procedural time, fluoroscopy time, and contrast volume. The more prevalent target CTO vessel was the left coronary artery in the TRA group and the right coronary artery in the TFA group. Higher J-CTO score, longer procedural time, and more contrast volume were seen in the TFA group. In comparison, the TRA group had better procedural success rate (odds ratio (OR), 0.846; 95% confidence interval (CI) 0.749-0.956) and less vascular complications (OR, 0.323; 95% CI 0.203-0.515), but similar retrograde success rate (OR, 0.965; 95% CI 0.382-2.435). In-hospital death (OR, 0.527; 95% CI 0.187-1.489) and major adverse cardiovascular events (OR, 0.729; 95% CI 0.504-1.054) did not differ between the groups. Overall, fewer vascular complications and higher procedural success rates were noted in the TRA CTO PCI population. However, similar retrograde success rates and clinical outcomes were noted between the groups., (© 2022. The Author(s).)

User opinion affects the performance of network reconstruction greatly since it plays a crucial role in the network structure. In this paper, we present a novel model for reconstructing the social network with community structure by taking into account the Hegselmann-Krause bounded confidence model of opinion dynamic and compressive sensing method of network reconstruction. Three types of user opinion, including the random opinion, the polarity opinion, and the overlap opinion, are constructed. First, in Zachary's karate club network, the reconstruction accuracies are compared among three types of opinions. Second, the synthetic networks, generated by the Stochastic Block Model, are further examined. The experimental results show that the user opinions play a more important role than the community structure for the network reconstruction. Moreover, the polarity of opinions can increase the accuracy of inter-community and the overlap of opinions can improve the reconstruction accuracy of intra-community. This work helps reveal the mechanism between information propagation and social relation prediction.

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are used in treating cardiovascular diseases. Previous studies indicated that ACEIs/ARBs may benefit cancer patients by inhibiting tumor angiogenesis and proliferation. The effect of ACEIs/ARBs on cancer survival in esophageal and gastric cancer is still unclear. This study is to investigate the association between ACEIs/ARBs usage and esophageal and gastric cancer prognosis., Methods: This retrospective cohort study identified esophageal and gastric cancer patients during 2008-2016 from the Taiwan Cancer Registry, and obtained medication usage and follow-up information from the National Health Insurance Research Database and Death Registry. Analysis groups were defined as ACEIs/ARBs user or non-user based on the usage of ACEIs/ARBs within the 6 months after cancer diagnosis. The stabilized inverse probability of treatment weighting using propensity scores was applied to balance covariates between study groups. We also used Kaplan-Meier estimates and Cox regression to compare survival outcome and estimate hazard ratios (HRs)., Results: We identified 14,463 and 21,483 newly-diagnosed esophageal and gastric cancer patients during 2008-2016. ACEIs/ARBs users were associated with lower risk of cancer-specific mortality, although only significantly in gastric cancer (gastric: adjusted HR = 0.87, 95% CI = 0.78-0.97; esophageal: adjusted HR =0.88, 95% CI = 0.76-1.02). A better survival outcome was observed among patients who received higher cumulative defined daily dose of ACEIs/ARBs., Conclusions: We found that using ACEIs/ARBs after cancer diagnosis were associated with lower risk of mortality. Our results add to the knowledge of the benefit of ACEIs/ARBs against mortality in individuals with esophageal/gastric cancer patients with hypertension., (© 2022. The Author(s).)

This study aims to assess the metal fume exposure of welders and to determine exposure rates for similar exposure groups in a shipyard through the use of Near-field/Far-field (NF/FF) mathematical model and Bayesian decision analysis (BDA) technique. Emission rates of various metal fumes (i.e., total chromium (Cr), iron (Fe), lead (Pb), manganese (Mn), and nickel (Ni)) were experimentally determined for the gas metal arc welding and flux cored arc welding processes, which are commonly used in shipyards. Then the NF/FF field model which used the emission rates were further validated by welding simulation experiment, and together with long-term operation condition data obtained from the investigated shipyard, the predicted long-term exposure concentrations of workers was established and used as the prior distribution in the BDA. Along with the field monitoring metal fume concentrations which served as the likelihood distribution, the posterior decision distributions in the BDA were determined and used to assess workers' long-term metal exposures. Results show that the predicted exposure concentrations (C p ) and the field worker's exposure concentrations (C m ) were statistically correlated, and the high R 2 (= 0.81-0.94) indicates that the proposed surrogate predicting method by the NF and FF model was adequate for predicting metal fume concentrations. The consistency in both prior and likelihood distributions suggests the resultant posterior would be more feasible to assess workers' long-term exposures. Welders' Fe, Mn and Pb exposures were found to exceed their corresponding action levels with a high probability (= 54%), indicating preventive measures should be taken immediately. The proposed approach provides a universal solution for conducting exposure assessment with usual limited number of personal exposure data., (© 2022. The Author(s).)

Background: Cancer-related fatigue (CRF) is the most common concomitant symptom in the treatment of colorectal cancer (CRC). Such patients often present with subjective fatigue state accompanied by cognitive dysfunction, which seriously affects the quality of life of patients., Aim: To explore the effects of cognitive behavior therapy (CBT) combined with Baduanjin exercise on CRF, cognitive impairment, and quality of life in patients with CRC after chemotherapy, and to provide a theoretical basis and practical reference for rehabilitation of CRC after chemotherapy., Methods: Fifty-five patients with CRC after radical resection and chemotherapy were randomly divided into either an experimental or a control group. The experimental group received the intervention of CBT combined with exercise intervention for 6 mo, and indicators were observed and measured at baseline, 3 mo, and 6 mo to evaluate the intervention effect., Results: Compared with the baseline values, in the experimental group 3 mo after intervention, cognitive function, quality of life score, and P300 amplitude and latency changes were significantly better ( P < 0.01). Compared with the control group, at 3 mo, the experimental group had significant differences in CRF, P300 amplitude, and quality of life score ( P < 0.05), as well as significant differences in P300 latency and cognitive function ( P < 0.01). Compared with the control group, at 6 mo, CRF, P300 amplitude, P300 latency, cognitive function and quality of life score were further improved in the experimental group, with significant differences ( P < 0.01). The total score of CRF and the scores of each dimension were negatively correlated with quality of life ( P < 0.05), while the total score of cognitive impairment and the scores of each dimension were positively correlated with quality of life ( P < 0.05)., Conclusion: CBT combined with body-building Baduanjin exercise can improve CRF and cognitive impairment in CRC patients after chemotherapy, and improve their quality of life., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: This study investigated differences in suicide and all-cause mortality from ICD-9-CM comorbid major depressive disorder (MDD) and type 2 diabetes mellitus (T2DM) depending on which was diagnosed first., Methods: A longitudinal administrative claims database including 2 million samples and national death registry data from 2000 through 2015 in Taiwan were used. Patients with newly diagnosed T2DM were identified and further classified into 3 groups: (1) MDD before T2DM, (2) T2DM without any diagnosis of MDD (from which matched controls were selected), and (3) MDD after T2DM, based on the sequential occurrence dates between incident T2DM and MDD. Multivariable Cox proportional hazard models were analyzed., Results: Both the MDD before T2DM and MDD after T2DM groups had significantly higher risks of all-cause mortality (adjusted hazard ratio [AHR] = 1.21; 95% CI, 1.08-1.35 and AHR = 1.55; 95% CI, 1.45-1.66, respectively) and committed suicide (AHR = 5.05; 95% CI, 2.46-10.37and AHR = 14.32; 95% CI, 7.44-27.55, respectively) than their matched controls, while the MDD before T2DM and MDD after T2DM groups exhibited differences in mortality (significant; P  < .0001) and death by suicide (nonsignificant) ., Conclusions: The study findings indicated suicide and mortality rates were higher in both the MDD before and MDD after T2DM groups when compared with matched controls. Public health initiatives are needed to survey and treat comorbid MDD with T2DM. Furthermore, additional studies are needed to clarify the underlying pathophysiology of the association between MDD and T2DM to find better suicide prevention strategies among those high-risk patients who have comorbid T2DM and MDD., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Objective: Burnout and suicidality are known risks for vascular surgeons above other surgical subspecialties, with surgical trainees at risk for exposure to factors that increase burnout. This study aimed to inform initiatives to improve wellness by assessing the prevalence of hazards in vascular training (mistreatment, duty-hour violations) and the rates of wellness outcomes (burnout, thoughts of attrition/specialty change/suicide). We hypothesized that mistreatment and duty-hour violations would predispose trainees to increased burnout., Methods: We performed a cross-sectional study of residents and fellows enrolled in accredited United States vascular surgery training programs using a voluntary, confidential survey administered during the 2020 Vascular Surgery In-Training Examination. The primary outcome assessed was burnout symptoms reported on a weekly basis or more frequently. The rates of wellness outcomes were measured. The association of mistreatment and duty hours with the primary outcome was modeled with multivariable logistic regression., Results: A total of 475 residents and fellows who were enrolled in one of 120 vascular surgery training programs completed the survey (84.2% response rate). Of 408 trainees completing burnout survey items, 182 (44.6%) reported symptoms of burnout. Fewer trainees reported thoughts of attrition (n = 42 [10.0%], specialty change (n = 35 [8.4%]), or suicide (n = 22 [4.9%]). Mistreatment was reported by 191 vascular trainees (47.3%) and was more common in female trainees (n = 63 [48.5%] reporting monthly or more frequently) compared with male trainees (n = 51 [18.6%]; P < .001). Duty-hour violations were also more commonly reported by female trainees (n = 31 [21.4%] reporting 3+ months in violation) compared with male trainees (n = 50 [16.2%]; P = .002). After controlling for race/ethnicity, postgraduate year, program type, and geography, female trainees were less likely to report burnout (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.28-0.86). Trainees experiencing mistreatment monthly or more were three times more likely to report burnout (OR, 3.09; 95% CI, 1.78-5.39). Frequency of duty-hour violations also increased the odds of reporting burnout (1-2 months in violation: OR, 2.09; 95% CI, 1.17-3.73; 3+ months in violation: OR, 3.95; 95% CI, 2.24-6.97)., Conclusions: Nearly one-half of vascular surgery trainees reported symptoms of burnout, which was associated with frequency of mistreatment and duty-hour violations. Interventions to improve well-being in vascular surgery must be tailored to the local training environment to address trainee experiences that contribute to burnout., (Copyright © 2021 Society for Vascular Surgery. All rights reserved.)

Background: Radiotherapy (RT) might lead to atherosclerotic plaque buildup and coronary artery stenosis of breast cancer (BC) survivors, and coronary artery calcium (CAC) might be a sign of preclinical atherosclerosis. This study explores possible determinants affecting the acceleration of CAC burden in BC patients after adjuvant RT., Methods: Female BC patients receiving adjuvant RT from 2002 to 2010 were included. All patients received noncontrast computed tomography (NCCT) of thorax before and after adjuvant RT. Their CAC burden was compared with healthy controls from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. The progression of the CAC burden was manifested by the increment of CAC percentiles (%CACinc)., Results: Ninety-four patients, including both left- and right-side BC, were enrolled in this study. From undergoing the first to second NCCT, the %CACinc in BC patients significantly increased rather than non-BC women. In addition, the %CACinc was significantly higher in left-side than right-side BC patients (p < 0.05), and significant differences in most heart outcomes were found between the two groups. Besides, the lower the mean right coronary artery (RCA) dose, the lower the risks of CAC percentiles increase ≥ 50% after adjusting the disease's laterality., Conclusions: A significantly higher accelerated CAC burden in BC patients than non-BC women represents that BC could affect accelerated CAC. A higher risk of accelerated CAC burden was found in left-side than right-side BC patients after adjuvant RT. A decrease of the mean RCA dose could reduce more than 50% of the risk of accelerated CAC burden in BC patients., (© 2021. The Author(s).)

Probiotic intake has been shown to improve certain physiological health indicators. We aimed to examine effects of Lactobacillus &nbsp; casei LTL1879, obtained from long-lived elderly volunteers, on blood biochemical, oxidative, and inflammatory markers and gut microbiota in twenty healthy, young volunteers. Volunteers were randomly divided into equal probiotic and placebo groups and changes in blood biochemical indicators, oxidative and inflammatory markers, and gut microbiota were examined after three weeks of probiotic intervention. The probiotic group's antioxidant levels were significantly enhanced post-intervention. Total antioxidant capacity (T-AOC) levels were significantly increased ( p < 0.0001), while malondialdehyde (MDA) levels decreased ( p < 0.05), and total superoxide dismutase (T-SOD) levels increased, but with no significant difference. In addition, Interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) levels were significantly up-regulated and down-regulated ( p < 0.05, respectively). Escherichia coli , Enterococcus , and Bacteroides expression was significantly reduced ( p < 0.05), while Clostridium leptum , Bifidobacterium , and Lactobacillus expression increased ( p < 0.05). Volunteer health status was quantified using principal components and cluster analysis, indicating that the probiotic group's overall score was higher than that of the placebo group. The results of this pilot study suggest L. casei LTL 1879 can significantly improve specific immune, oxidative, and gut microbiota characteristics related to health factors.

The pathogenesis of nephrotic syndrome is unclear. We conducted a nationwide population-based cohort study to examine the associations between preterm births and subsequent development of NS. NS was defined as ≥ 3 records with ICD-9-CM codes for NS in hospital admission or outpatient clinic visits. To avoid secondary nephrotic syndrome or nephritis with nephrotic range proteinuria, especially IgA nephropathy, we excluded patients with associated codes. A total of 78,651 preterm infants (gestational age < 37 weeks) and 786,510 matched term infants born between 2004 and 2009 were enrolled and followed until 2016. In the unadjusted models, preterm births, maternal diabetes, and pregnancy induced hypertension were associated with subsequent NS. After adjustment, preterm births remained significantly associated with NS (p = 0.001). The risk of NS increased as the gestational age decreased (p for trend < 0.001). Among the NS population, preterm births were not associated with more complications (Hypertension: p = 0.19; Serious infections: p = 0.63, ESRD: p = 0.75) or a requirement for secondary immunosuppressants (p = 0.61). In conclusion, preterm births were associated with subsequent NS, where the risk increased as the gestational age decreased. Our study provides valuable information for future pathogenesis studies., (© 2021. The Author(s).)

To investigate associations between isoniazid for latent tuberculosis and risk of severe hepatitis, affecting patients with rheumatoid arthritis or ankylosing spondylitis whose treatment includes tumor necrosis factor inhibitors. Our self-controlled case series study analyzed Taiwan's National Health Insurance Database from 2003 to 2015 to identify RA or AS patients, aged ≥ 20 years, receiving TNF inhibitors and a 9-month single isoniazid treatment. The outcome of interest was hospitalization due to severe hepatitis. We defined risk periods by isoniazid exposure (days): 1-28, 29-56, 57-84, 85-168, 169-252, and 253-280. To compare risk of severe hepatitis in exposed and non-exposed periods, we performed conditional Poisson regressions to generate incidence rate ratios (IRR) and 95% confidence intervals, with adjustment of patients' baseline covariates including age, sex, HBV, HCV and related medication. Of 54,267 RA patients and 137,889 AS patients identified between 2000 and 2015, 11,221 (20.7%) RA and 4,208 (3.1%) AS patients underwent TNFi therapy, with 722 (5%) receiving isoniazid for latent tuberculosis. We identified 31 incident cases (4.3%) of hospitalization due to severe hepatitis. Of these hospitalization events, 5 occurred in the exposed periods, 25 occurred in the INH unexposed periods, and 1 occurred in the pre-exposure period. Compared with non-exposure, the risk of severe hepatitis was higher in exposed periods (incidence rate ratio [IRR]: 5.1, 95% CI: 1.57-16.55), especially 57-84 days (IRR: 17.29, 95% CI: 3.11-96.25) and 85-168 days (IRR:10.55, 95% CI: 1.90-58.51). The INH related fatal hepatotoxicity was not identified in our study. Our findings suggest an association between risk of severe hepatitis and exposure to isoniazid in patients with RA or AS under TNFi therapy, particularly within the exposed period 57-168 days. A close monitoring of liver function is mandatory to minimize the risk, especially within the first 6 months after initiation of 9 months isoniazid., (© 2021. The Author(s).)

Background: Prior studies comparing the efficacy of laparoscopic (LHR) and open hepatic resection (OHR) have not evaluated inpatient costs., Methods: We conducted a retrospective cohort study using the Healthcare Cost and Utilization Project State Inpatient Databases to identify patients undergoing hepatic resection between 2010 and 2014., Results: 10,239 patients underwent hepatic resection. 865 (8%) underwent LHR and 9374 (92%) underwent OHR. On adjusting for hospital volume, patients undergoing LHR had a lower risk of respiratory (OR 0.64, 95% CI [0.52, 0.78]), wound (OR 0.48; 95% CI [0.29, 0.79]) and hematologic (OR 0.57; 95% CI [0.44, 0.73]) complication as well as a lower risk of being in the highest quartile of cost (0.58; 95% CI [0.43, 0.77]) than those undergoing OHR. Patients undergoing LHR in very high volume (>314 hepatectomies/year) centers had lower risk-adjusted 90-day aggregate costs of care than those undergoing OHR (-$8022; 95% CI [-$11,732, -$4311)., Discussion: Laparoscopic partial hepatectomy is associated with lower risk of postoperative complication than OHR. This translates to lower aggregate costs in very high-volume centers., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: To evaluate the role of postoperative treatment in parotid gland carcinoma (PGC) based on risk stratification., Material and Methods: A total of 301 PGC patients were retrospectively analyzed using risk stratification. The Kaplan-Meier method and Cox analysis were performed to conduct survival analysis., Results: In the high-risk group, those treated with postoperative radiotherapy (RT) had a better 5-year disease-free survival (DFS) than those treated with surgery alone. In the low-risk group, both surgery + RT and surgery +  chemotherapy (CT) significantly improved DFS when compared with surgery alone. Cox analysis showed that patients who underwent surgery + RT or surgery + CT had a lower risk of disease progression than those who underwent surgery alone in the low-risk group. In the high-risk group, patients who underwent surgery + RT had a lower risk of disease progression., Conclusions: Postoperative RT showed considerable benefit in improving disease control in patients with PGC, even in those without high-risk factors., (© 2021 Wiley Periodicals LLC.)

Background: Ocular adverse events are common dose-limiting toxicities in cancer patients treated with HSP90 inhibitors, such as AUY922; however, the pathology and molecular mechanisms that mediate AUY922-induced retinal toxicity remain undescribed., Methods: The impact of AUY922 on mouse retinas and cell lines was comprehensively investigated using isobaric tags for relative and absolute quantitation (iTRAQ)‑based proteomic profiling and pathway enrichment analysis, immunohistochemistry and immunofluorescence staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, MTT assay, colony formation assay, and western blot analysis. The effect of AUY922 on the Transient Receptor Potential cation channel subfamily M member 1 (TRPM1)-HSP90 chaperone complex was characterized by coimmunoprecipitation. TRPM1-regulated gene expression was analyzed by RNAseq analysis and gene set enrichment analysis (GSEA). The role of TRPM1 was assessed using both loss-of-function and gain-of-function approaches., Results: Here, we show that the treatment with AUY922 induced retinal damage and cell apoptosis, dysregulated the photoreceptor and retinal pigment epithelium (RPE) layers, and reduced TRPM1 expression. Proteomic profiling and functional annotation of differentially expressed proteins reveals that those related to stress responses, protein folding processes, regulation of apoptosis, cell cycle and growth, reactive oxygen species (ROS) response, cell junction assembly and adhesion regulation, and proton transmembrane transport were significantly enriched in AUY922-treated cells. We found that AUY922 triggered caspase-3-dependent cell apoptosis, increased ROS production and inhibited cell growth. We determined that TRPM1 is a bona fide HSP90 client and characterized that AUY922 may reduce TRPM1 expression by disrupting the CDC37-HSP90 chaperone complex. Additionally, GSEA revealed that TRPM1-regulated genes were associated with retinal morphogenesis in camera-type eyes and the JAK-STAT cascade. Finally, gain-of-function and loss-of-function analyses validated the finding that TRPM1 mediated the cell apoptosis, ROS production and growth inhibition induced by AUY922., Conclusions: Our study demonstrates the pathology of AUY922-induced retinal toxicity in vivo. TRPM1 is an HSP90 client, regulates photoreceptor morphology and function, and mediates AUY922-induced cytotoxicity., (© 2021. The Author(s).)

Objective: To establish a method for extracting Listeria monocytogenes membrane vesicles (LM-MVs) and to analyze the characteristics of LM-MVs and their ability to induce innate immune effect in vitro so as to lay the foundation for research into using LM-MVs as vaccine carrier and drug delivery platform., Methods: The membrane vesicles secreted by Listeria monocytogenes were extracted through a continuous process, including culturing, centrifugation, filtration, ultrafiltration concentration and ultracentrifugation. The morphological characteristics of LM-MVs were observed with transmission electron microscope, and particle size distribution were measured by dynamic light scattering analysis. SDS-PAGE and Western blot were used to analyze the protein composition of LM-MVs. CCK-8 cell proliferation and toxicity determination experiments were done to analyze their effect on the proliferation of innate immune cells, and qPCR was used to analyze their ability to induce innate immune responses., Results: A method for extracting LM-MVs was successfully established. Under the transmission electron microscope, LM-MVs presented a nearly circular film-like structure, and dynamic light scattering analysis showed that their sizes were between 65 and 190 nm. SDS-PAGE and Western blot showed that LM-MVs contained proteins, including listeriolysin O (LLO). CCK-8 cell proliferation and toxicity experiment showed that after intervention with 10, 20 and 50 μg/mL of LM-MVs for 24 hours, the proliferation rate of DC 2.4 mouse dendritic cell line was higher than that of non-interventional DC 2.4 cells ( P <0.05); after intervention with 0.1, 1, 10, 20 and 50 μg/mL of LM-MVs for 24 hours, the proliferation rate of RAW 264.7 cells was higher than that of non-interventional RAW 264.7 cells ( P <0.01). The results of qPCR showed that, after intervention with 50 μg/mL of LM-MVs, the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 in RAW 264.7 cells were higher than those of non-intervention control cells ( P <0.05)., Conclusions: The method established in the study can be used to extract LM-MVs. The extracted LM-MVs have a diameter of 65-190 nm and a nearly circular membrane-like structure. They can secrete a variety of protein components and stimulate innate immune responses., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Premature atrial complexes (PACs) have been suggested to increase the risk of adverse events. The distribution of PAC burden and its dose-response effects on all-cause mortality and cardiovascular death had not been elucidated clearly. We analyzed 15,893 patients in a medical referral center from July 1st, 2011, to December 31st, 2018. Multivariate regression driven by ln PAC (beats per 24 h plus 1) or quartiles of PAC burden were examined. Older group had higher PAC burden than younger group (p for trend < 0.001), and both genders shared similar PACs distribution. In Cox model, ln PAC remained an independent risk factor for all-cause mortality (hazard ratio (HR) = 1.09 per ln PAC increase, 95% CI = 1.06‒1.12, p < 0.001). PACs were a significant risk factor in cause-specific model (HR = 1.13, 95% CI = 1.05‒1.22, p = 0.001) or sub-distribution model (HR = 1.12, 95% CI = 1.04‒1.21, p = 0.004). In ordinal PAC model, 4th quartile group had significantly higher risk of all-cause mortality than those in 1st quartile group (HR = 1.47, 95% CI = 1.13‒1.94, p = 0.005), but no difference in cardiovascular death were found in competing risk analysis. In subgroup analysis, the risk of high PAC burden was consistently higher than in low-burden group across pre-specified subgroups. In conclusion, PAC burden has a dose response effect on all-cause mortality and cardiovascular death.

Background: The optimal surgical technique for the fixation of inferior pole patellar fracture remains controversial. The aims of this study were (1) to compare clinical and radiological outcomes following fixation of inferior pole patellar fracture by using tension band wire (TBW) and transosseous reattachment (TOR) without excision of the bony fragment and (2) to determine the risk factors for postoperative radiological loss of reduction., Methods: For this retrospective cohort study, consecutive patients with inferior pole patellar fracture between January 2010 and December 2017 were recruited. The patients were grouped according to their fixation method (TBW or TOR), and demographic data, clinical outcomes, and postoperative Insall-Salvati (IS) ratio were analyzed. Then, the patients were grouped according to radiological loss of reduction, the possible risk factors for loss of reduction were identified, and odds ratios were calculated., Result: This study included 55 patients with inferior pole patellar fracture; 30 patients were treated using TBW and 25 were treated using TOR. Clinical failure occurred in two patients in the TBW group (7%) and three in the TOR group (12%). The rate of radiological loss of reduction was significant higher in the TOR group, whereas removal of implants was significantly more common in the TBW group. Patella baja was noted immediately after surgery in the TOR group, but the IS ratios of the two groups were similar after 3 months. Fracture displacement of more than 30 mm was the only independent risk factor for postoperative radiological loss of reduction., Conclusion: For treating inferior pole patellar fracture, both TWB and TOR were effective and had a low clinical failure rate. In 60% of patients undergoing TBW fixation, however, additional surgery was required to remove the implants. Patella baja occurred immediately following TOR, but the patellar height was similar to that in the TBW group after 3 months. Surgeons should be aware of the high risk of postoperative radiological loss of reduction, especially when the fracture displacement is more than 30 mm.

Background: To assess the clinical and survival features of nasopharyngeal carcinoma (NPC) with consistently negative Epstein-Barr virus (EBV) DNA level., Methods: Propensity score matching (PSM) method was used to create well-balanced cohorts. Kaplan-Meier method and Cox proportional hazards models were performed to conduct survival analysis., Results: Four hundred and eighty patients were enrolled. Patients with consistently negative plasma EBV DNA level had a greater chance to present a relatively earlier T and N classification compared with those with positive EBV DNA level (p < .001; p = .015). And patients with consistently negative EBV level were significantly associated with preferable 3-year DFS (95.0% vs. 84.4%, p = .004), DMFS (98.3% vs. 89.4%, p = .009), and OS (100% vs. 97.6%, p = .004)., Conclusions: NPC patients with consistently negative EBV DNA level performed an earlier clinical stage and negative EBV DNA level was related to preferable survival outcomes., (© 2021 Wiley Periodicals LLC.)

The structure of a social network plays a crucial role for dynamic analysis, which is invisible in most scenes. In this paper, we present a model for reconstructing the social network by taking into account the public opinion diffusion dynamic model for specific agenda. First, the initial polarity attitude of users i for the agenda, o i , is set in the range [-1,1], where negative and positive attitudes are set as -1 and 1, respectively, while 0 means that user i's attitude is uncertain. Second, we present an optimization model for detecting the relationship among each pair of users based on the generated public observable information. The experimental results for four synthetic networks and three real-world social networks show that the reconstruction accuracy depends on the uncertainty of the initial attitudes greatly. This work is helpful for revealing the structure of social networks in terms of public information.

Ratooning is an important cultivation practice in sugarcane production around the world, with underground buds on the remaining stalk acting as the source for establishment of a subsequent ratoon crop. However, the optimal depth of cutting during harvest in terms of yield and root growth remains unknown. We carried out a two-year field study to determine the effects of three cutting depths (0, 5 and 10 cm below the surface) ratoon cane root and yield. Results showed that cutting to a depth of 5 cm increased the root fresh weight and root volume by 21-59% and 41-127%, respectively, compared to cutting depths of 0 and 10 cm. Remarkably, cutting to a depth of 5 cm also had a significant effect on the development of fine roots, which is closely linked to cane yield. The effect was particularly noticeable in terms of two root traits, root volume and the surface area of roots with a diameter of 1.0-2.0mm, and root length and the number of root tips in roots with a diameter of 0-0.5mm. As a result, a cutting depth of 5 cm below the surface increased cane yield by 43 and 28% compared to depths of 0 and 10 cm below the surface, respectively. Overall, these findings suggest that a cutting depth of 5 cm is optimal in terms of sugarcane yield, largely due to the enhanced effect on root traits, especially the development of fine roots. These findings will help optimize sugarcane ratoon management and improve the ratoon cycle., Competing Interests: The authors have declared that no competing interests exist.

We assess the safety and feasibility of the left hepatic vein preferential approach (LHVPA) based on left hepatic vein (LHV) anatomy for living donor laparoscopic left lateral sectionectomy (LLLS). Data from 50 donors who underwent LLLS in Huashan Hospital from October 2016 to November 2019 were analyzed retrospectively. On the basis of the classification of the LHV anatomy, the vein was defined as the direct import type, upper branch type, or indirect import type. A subgroup analysis was performed to compare the outcomes between the LHVPA and non-LHVPA groups. All 50 patients underwent pure LLLS. The mean operative duration was 157.5 ± 29.7 minutes. The intraoperative blood loss was 160.4 ± 97.5 mL. No complications more severe than grade 3 occurred. LHVPA was applied in 13 patients, whereas non-LHVPA was applied in 10 patients with the direct import type and upper branch type anatomy. The operative duration was shorter in the LHVPA group than the non-LHVPA group (142.7 ± 22.0 versus 173.0 ± 22.8 minutes; P = 0.01). Intraoperative blood loss was reduced in the LHVPA group compared with the non-LHVPA group (116.2 ± 45.6 versus 170.0 ± 63.3 mL; P = 0.02). The length of the LHV reserved extrahepatically in the LHVPA group was longer than in the non-LHVPA group (4.3 ± 0.2 versus 3.3 ± 0.3 mm; P = 0.01). Fewer reconstructions of the LHV in the direct import type anatomy were required for the LHVPA group than for the non-LHVPA group (0/8 versus 4/6). LHVPA based on the LHV anatomy is recommended in LLLS because it can further increase the safety and the efficiency of surgery for suitable donors., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

The COronaVIrus Disease 2019 (COVID-19), which developed into a pandemic in 2020, has become a major healthcare challenge for governments and healthcare workers worldwide. Despite several medical treatment protocols having been established, a comprehensive rehabilitation program that can promote functional recovery is still frequently ignored. An online consensus meeting of an expert panel comprising members of the Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation was held to provide recommendations for rehabilitation protocols in each of the five COVID-19 stages, namely (1) outpatients with mild disease and no risk factors, (2) outpatients with mild disease and epidemiological risk factors, (3) hospitalized patients with moderate to severe disease, (4) ventilator-supported patients with clear cognitive function, and (5) ventilator-supported patients with impaired cognitive function. Apart from medications and life support care, a proper rehabilitation protocol that facilitates recovery from COVID-19 needs to be established and emphasized in clinical practice., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020. Published by Elsevier B.V.)

Reducing the application of chemical fertilizer and increasing fertilizer efficiency can contribute to the sustainable development of agriculture. To evaluate the impacts of N fertilizer reduction and biochar application on soil organic carbon active components and mineralization in yellow soil, an experiment was carried out with five different substitution rates of chemical N fertilizer by biochar under the same rate of N input, i.e ., 0, 10%, 20%, 30%, 40% (CK, T 1 -T 4 ). The results showed that chemical N fertilizer reduction combined with biochar application could significantly improve soil organic carbon (SOC), the magnitude of which was proportional to the amount of biochar application. Under the condition of 20% substitution rate (T 2 ), soil microbial biomass carbon (MBC) and readily oxidized carbon (ROC) were the highest with 293.68 mg·kg -1 and 250.00 mg·kg -1 , respectively, but the concentration of soil dissolved organic carbon (DOC) was the lowest. SOC mineralization rate reached the highest on the third day of incubation. Then, it decreased rapidly in the early period (day 3 of incubation to day 6), decreased slowly in the middle period (day 6 of incubation to day 18), and stabilized in the later period (day 18 of incubation to day 30). There was a logarithmic relationship between mineralization rate of soil organic carbon and incubation time. SOC cumulative mineralization amount and cumulative mineralization rate were the lowest in the T 2 treatment with 0.66-0.86 g·kg -1 and 2.9%-4.0%, respectively. As the substitution rate of chemical N fertilizer by biochar increased, rice yield increased firstly and then decreased. Rice yield in the T 2 treatment was the highest, which increased by 13.4% compared with the CK. The substitution of 20% chemical N fertilizer with biochar (5 t·hm -2 ) could effectively improve the contents of SOC, MBC, ROC, and rice yield, reduce the cumulative mineralization amount of organic carbon and cumulative mineralization rate, and enhance the capacity of soil carbon sequestration. Hence, it could be the most effective fertilizer practice for improving soil fertility and rice yield in paddy field of yellow soil in Guizhou Province.

Background Context: Targeting chemokines or chemokine receptors is a promising treatment strategy for diseases with chronic inflammation such as rheumatoid arthritis and discogenic pain. Identifying specific molecules and determining their effectiveness in animal models are the first steps in developing these treatments. Macrophage markers have been detected in the intervertebral disc tissues of patients with disc degenerative disease and discogenic pain and in different animal models. Macrophage recruitment into the disc may play a role in initiation of inflammation and if unresolved may lead to chronic inflammation and subsequent back pain., Purpose: The objectives of these studies are to (1) identify chemokine receptor antagonists that can block macrophage migration induced by disc cells in vitro and (2) determine if intradiscal treatment with these antagonists can reduce disc inflammation and degeneration in vivo., Study Design: In vitro migration assays were used to test effectiveness of chemokine receptor antagonists to block macrophage migration induced by disc cells. The rabbit annular puncture model was used to test for anti-inflammatory and regenerative effects of chemokine receptor antagonist treatment in vivo., Methods: In vitro - THP-1 human monocytic cell line and freshly isolated rabbit primary splenocytes were assayed for migration using 3 µm Corning Transwell inserts with conditioned media of interleukin (IL)-1β treated human or rabbit disc cells. Inhibition of macrophage migration was evaluated using different concentrations of small molecule antagonists of C-C chemokine receptor (CCR)1 and CCR2. In vivo - New Zealand White rabbits (n=40) underwent disc puncture and intradiscal treatment with saline, CCR1 or CCR2 antagonists within the same procedure. X-ray and magnetic resonance (MR) images and serum samples were taken for disc height, MRI grade and IL-8 serum level analyses. Intervertebral discs were isolated for RNA analysis of inflammatory and disc phenotypic markers and for immunohistochemical analysis of macrophage marker, RAM11. The outcome measures were compared between the three treatment groups. These studies were funded by a research grant from AO Foundation, Switzerland (Project no S-14-86A; 120000 CHF). CCR1 and CCR2 antagonists were kindly provided by ChemoCentryx (Mountain View, CA)., Results: In vitro migration assays showed that THP-1 migration induced by disc cells was blocked by CCR2 antagonist more effectively than CCR1 antagonist, while rabbit splenocyte migration was inhibited by CCR1 antagonist and not the other. In the rabbit annular puncture model, rabbit discs treated with CCR1 antagonist had significantly better MRI grades than those treated with CCR2 antagonist at 6 weeks post-treatment. Gene expression studies demonstrate that discs treated with CCR1 or CCR2 antagonists expressed less inflammatory markers than saline-treated discs at 3 weeks post-treatment. Although CCR2 antagonist treatment did not reduce inflammatory marker expression at 6 weeks, discs treated with CCR1 antagonist expressed less inflammatory markers and also a higher ratio of collagen type 2 to collagen type 1 genes indicating favorable disc matrix production. There were no significant differences between all three treatment groups in regards to disc height indexes, IL-8 serum levels or macrophage marker detection., Conclusions: These studies have identified that small molecule antagonists against CCR2 and CCR1 were respectively effective in blocking THP-1 and rabbit splenocyte migration induced by disc cells in vitro. Further, both CCR2 and CCR1 antagonist intradiscal treatments were effective in reducing disc inflammation at an early time point of 3 weeks. Lastly, only CCR1 antagonist demonstrated anti-inflammatory effects and better MRI grades at 6 weeks., Clinical Significance: Our preclinical studies demonstrate that CCR1 and CCR2 antagonist delivery through intradiscal injection is sufficient to reduce disc inflammation at early time points, whereas CCR1 antagonists had longer term anti-inflammatory effects. Clinical studies have found that CCR1 antagonist was safe, tolerable and clinically active in reducing inflammation in rheumatoid arthritis patients. These studies suggest that CCR1 antagonist may be a promising biological treatment to reduce disc inflammation that translates to back pain relief., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Forests play an important role in terrestrial carbon cycles. The mechanism underlying carbon balance in temperate deciduous broad-leaved forests is not clear. In this study, net ecosystem exchange (NEE) and environmental factors, including air temperature ( T a ), soil temperature ( T s ), photosynthetically active radiation (PAR), vapor pressure deficit (VPD), soil water content (SWC) and precipitation ( P ) were continually measured using eddy covariance techniques in 2019 in a deciduous broad-leaved forest in Songshan, Beijing. We analyzed the characteristics of NEE and its response to environmental factors. The results showed that, at diurnal scale, the monthly averaged NEE exhibited a "U" shape curve ( i.e ., being a carbon sink over daytime while being a carbon source during nighttime) over the growing season. During the non-growing season, NEE was positive ( i.e ., carbon source) at diurnal scale. At the seasonal scale, NEE exhibited a unimodal curve. The annual cumulative NEE was -111 g C·m -2 ·a -1 . Annual ecosystem respiration was 555 g C·m -2 ·a -1 , while gross ecosystem productivity was 666 g C·m -2 ·a -1 . Carbon sequestration peaked in June, while emission peaked in November. PAR was the dominant factor affecting daytime NEE (NEE d ). VPD was the main factor that indirectly affected daytime NEE d , with an optimal VPD value that maximizes daytime NEE around 1-1.5 kPa. Soil temperature was the main factor affecting nighttime NEE (NEE n ). SWC was a limiting factor for NEE n . Too high or too low SWC would inhibit NEE n , with an optimal SWC value of 0.28 m 3 ·m -3 .

Background: The development of measures of child maltreatment for the Chinese population were limited until the Chinese version of the ISPCAN Child Abuse Screening Tools - Children's Home version (ICAST-CH-C) was proposed. Although the ICAST-CH-C was found to be effective in assessing the scope and prevalence of child maltreatment, it has several potential drawbacks. The time that is required to complete the ICAST-CH-C scale is longer than usual for a 36-item scale, because many of its items have one or more follow-up questions. Moreover, each item requires child victims to recall unpleasant experiences. Both phenomena can cause increases in invalid responses and in turn damage the data quality., Objective: The goal of this study was to propose a short form of the ICAST-CH-C (called the SC-ICAST-CH) to reduce the test length and response time in order to improve the measurement quality., Participants and Setting: A dataset from a national survey of 5236 adolescents in Taiwan was used., Methods: A multidimensional version of the rating scale model (MRSM) was fitted to the data. The model parameters were estimated with the ConQuest software., Results: The results indicated the reliability of the SC-ICAST-CH was fairly good, with only 61 % of the original test length. Disordered thresholds were found in all five subscales; the underlying reasons for this phenomenon need further investigation. Specific cultural differences related to item retention/removal decisions were also discussed., Conclusion: The efficient, shorter SC-ICAST-CH was shown to be a valid and reliable instrument for assessing the prevalence of child maltreatment., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hepatitis B is the most prevalent viral hepatitis worldwide, affecting approximately one-third of the world's population. Among HBV factors, the surface protein is the most sensitive biomarker for viral infection, given that it is expressed at high levels in all viral infection phases. The large HBV surface protein (LHBs) contains the integral pre-S1 domain, which binds to the HBV receptor sodium taurocholate co transporting polypeptide on the hepatocyte to facilitate viral entry. The accumulation of viral LHBs and its prevalent pre-S mutants in chronic HBV carriers triggers a sustained endoplasmic reticulum (ER) overload response, leading to ER stress-mediated cell proliferation, metabolic switching and genomic instability, which are associated with pro-oncogenic effects. Ground glass hepatocytes identified in HBV-related hepatocellular carcinoma (HCC) patients harbor pre-S deletion variants that largely accumulate in the ER lumen due to mutation-induced protein misfolding and are associated with increased risks of cancer recurrence and metastasis. Moreover, in contrast to the major HBs, which is decreased in tumors to a greater extent than it is in peritumorous regions, LHBs is continuously expressed during tumorigenesis, indicating that LHBs serves as a promising biomarker for HCC in people with CHB. Continuing efforts to delineate the molecular mechanisms by which LHBs regulates pathological changes in CHB patients are important for establishing a correlation between LHBs biomarkers and HCC development.

Ampullary adenocarcinoma is a rare gastrointestinal cancer in which WNT signalling dysregulation has been previously reported. Secreted frizzled related protein 1 (SFRP1) is one of the extracellular ligands of WNT signalling. We performed bioinformatics analyses of SFRP1 expression in human cancer. Microarray analysis of SFRP1 in periampullary adenocarcinoma was obtained from the Gene Expression Omnibus GSE39409 dataset. SFRP1 expression in ampullary adenocarcinoma was detected by immunohistochemistry staining and correlated with patients' clinical outcomes. Our results showed that SFRP1 expression had different clinical applications in all types of human cancer. No detected alteration of SFPR1 gene and SFRP1 expression in ampullary adenocarcinoma was lower than that in other periampullary adenocarcinomas. However, high expression levels of SFRP1 protein were correlated with cancer recurrence, peritoneal carcinomatosis and poor patient prognosis. Gene set enrichment analysis showed downregulation of multiple WNT-related genes in primary culture cells from ampullary adenocarcinoma, but SFRP1 expression was increased. We found an interaction between WNT, bone morphogenetic protein and hedgehog signalling with SFRP1. Furthermore, a high expression of SFRP1 predicted poor prognosis for ampullary adenocarcinoma patients. Because it is a multifunctional protein, SFRP1 targeting serves as a potential therapy for ampullary adenocarcinoma patients.

Background: Infections still represent the main factors influencing morbidity and mortality following liver transplantation. This study aimed to evaluate the incidence and risk factors for infection and survival after liver transplantation., Methods: We retrospectively examined medical records in 210 liver recipients who underwent liver transplantation between April 2015 and October 2017 in our hospital. Clinical manifestations and results of pathogen detection test were used to define infection. We analyzed the prevalence, risk factors and prognosis of patients with infection., Results: The median follow-up was 214 days; the incidence of infection after liver transplantation was 46.7% (n = 98) which included pneumonia (43.4%), biliary tract infection (21.9%), peritonitis (21.4%) and bloodstream infection (7.6%). Among the pathogens in pneumonia, the most frequently isolated was Acinetobacter baumanii (23.5%) and Klebsiella pneumoniae (21.2%). Model for end-stage liver disease (MELD) score (OR = 1.083, 95% CI: 1.045-1.123; P < 0.001), biliary complication (OR = 4.725, 95% CI: 1.119-19.947; P = 0.035) and duration of drainage tube (OR = 1.040, 95% CI: 1.007-1.074; P = 0.017) were independent risk factors for posttransplant infection. All-cause mortality was 11.0% (n = 23). The prognostic factors for postoperative infection in liver recipients were prior-transplant infection, especially pneumonia within 2 weeks before transplantation. Kaplan-Meier curves of survival showed that recipients within 2 weeks prior infection had a significantly lower cumulative survival rate compared with those without infection (65.2% vs. 90.0%; hazard ratio: 4.480; P < 0.001)., Conclusions: Infection, especially pneumonia within 2 weeks before transplantation, complication with impaired renal function and MELD score after 7 days of transplantation was an independent prognostic factor for postoperative infection in liver transplant recipients., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2020. Published by Elsevier B.V.)

Metabolic disease, including diabetes mellitus, hypertension, dyslipidemia, obesity, and hyperuricemia, is a common complication after liver transplantation and a risk factor for cardiovascular disease and death. The development of metabolic disease is closely related to the side effects of immunosuppressants. Therefore, optimization of the immunosuppressive regimen is very important for the prevention and treatment of metabolic disease. The Chinese Society of Organ Transplantation has developed an expert consensus on the management of metabolic diseases in Chinese liver transplant recipients based on recent studies. Emphasis is placed on the risk factors of metabolic diseases, the effect of immunosuppressants on metabolic disease, and the prevention and treatment of metabolic diseases., Competing Interests: Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Drought is an important factor which limits growth of sugarcane. To elucidate the physiological and biochemical mechanisms of tolerance, a pot experiment was conducted at Sugarcane Research Institute, Kaiyuan, China. Two genotypes (Yuetang 93-159-sensitive and Yunzhe 05-51-tolerant), were subjected to three treatments; 70±5% (control), 50±5% (moderate drought) and 30±5% (severe drought) of soil field capacity. The results demonstrated that drought induced considerable decline in morpho-physiological, biochemical and anatomical parameters of both genotypes, with more pronounced detrimental effects on Yuetang 93-159 than on Yunzhe 05-51. Yunzhe 05-51 exhibited more tolerance by showing higher dry biomass, photosynthesis and antioxidant enzyme activities. Compared with Yuetang 93-159, Yunzhe 05-51 exhibited higher soluble sugar, soluble protein and proline contents under stress. Yunzhe 05-51 illustrated comparatively well-composed chloroplast structure under drought stress. It is concluded that the tolerance of Yunzhe 05-51 was attributed to improved antioxidant activities, osmolyte accumulation and enhanced photosynthesis. These findings may provide valuable information for future studies on molecular mechanism of tolerance., Competing Interests: The authors have declared that no competing interests exist.

Objective: Acute liver injury (ALI) is mainly characterized by the symptom of metabolic disorders, homeostasis unbalance, and loss of liver function. There are no effective treatment methods at present stage except the liver transplantation. Effective treatment for early ALI is of great significance for the treatment of liver injury thereof. Glycyrrhizin (GL) is a promising inhibitor of the high-mobility group box-1 gene (HMGB1) which is expressed much higher in an inflammatory injury. However, it is not clear whether GL improves ALI via the inhibition of HMGB1. The present study is to probe the function and mechanism of glycyrrhizin on acute liver injury., Materials and Methods: The expression of HMGB1 and inflammation in liver macrophages were analyzed. Lipopolysaccharide (LPS) was used in stimulating the macrophages to activate inflammatory response and recombined human HMGB1 was used to resist the function of GL to explore whether GL acted via the target of HMGB1. Then, LPS injection was utilized to induce ALI in mice, and then we evaluated GL treatment in ALI model., Results: The results showed that the expressions of HMGB1 and inflammatory factors were markedly increased in LPS-activated liver macrophages. GL inhibited the progress of macrophages inflammation by restraining HMGB1, and the administration of GL could reverse the effects of LPS-induced ALI in mice. Moreover, PI3K/mTOR pathway was significantly suppressed by GL application., Conclusions: These results suggest that GL prevents inflammation in liver macrophages via inhibition of HMGB1. GL restrains inflammation and cell apoptosis by inhibiting HMGB1 via PI3K/mTOR signaling pathway in ALI. GL may become a novel drug for the therapy of ALI in the future.

Aim: Immunological checkpoint therapy is considered a powerful method for cancer therapy and acts by re-activating autologous T cells to kill the cancer cell. Myocarditis cases have been reported in cancer patients after immunological therapy; for example, nivolumab treatment is a monoclonal antibody that blocks programmed cell death-1/programmed cell death ligand-1 ligand interaction. This project provided insight into the inflammatory response as a benchmark to investigate the potential cardiotoxic effect of T cell response to the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis in regulating cardiomyocyte injury in vitro., Methods and Results: We investigated cardiomyopathy resulted from the PD-1/PD-L1 axis blockade using the anti-PD-1 antibody in Rockefeller University embryonic stem cells-derived cardiomyocytes (RUES2-CMs) and a melanoma tumor-bearing murine model. We found that nivolumab alone did not induce inflammatory-related proteins, including PD-L1 expression, and did not induce apoptosis, which was contrary to doxorubicin, a cardiotoxic chemotherapy drug. However, nivolumab was able to exacerbate the immune response by increasing cytokine and inflammatory gene expression in RUES2-CMs when co-cultured with CD4 + T lymphocytes and induced apoptosis. This effect was not observed when RUES2-CMs were co-cultured with CD8 + T lymphocytes. The in vivo model showed that the heart function of tumor-bearing mice was decreased after treatment with anti-PD-1 antibody and demonstrated a dilated left ventricle histological examination. The dilated left ventricle was associated with an infiltration of CD4 + and CD8 + T lymphocytes into the myocardium. PD-L1 and inflammatory-associated gene expression were significantly increased in anti-PD-1-treated tumor-bearing mice. Cleaved caspase-3 and mouse plasma cardiac troponin I expressions were increased significantly., Conclusion: PD-L1 expression on cardiomyocytes suppressed T-cell function. Blockade of PD-1 by nivolumab enhanced cardiomyocyte inflammation and apoptosis through the enhancement of T-cell response towards cardiomyocytes.

Background: Helicobacter pylori infection is known to alter growth-related hormones and affect growth in young children. However, it is still unknown whether maternal H. pylori infection has an impact on the levels of cord blood growth-related hormones and whether this can predict intrauterine growth restriction and poor physical and neurodevelopmental outcomes in children. This study aimed to examine associations between maternal H. pylori infection and pregnancy-related adverse events, fetal growth and early childhood development., Methods: In this prospective cohort study, we recruited singleton pregnant women without major medical illnesses from January 2014 to January 2015. Seropositivity for H. pylori was defined as > 12 U/ml of anti-H. pylori IgG in maternal serum. Demographic data and pregnancy-related medical issues of the cohort were documented. Cord blood levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), insulin, and ghrelin were determined using ELISA. The growth of the included neonates was monitored annually for up to 3 years, and cognitive development was assessed using the comprehensive developmental inventory for infants and toddlers (CDIIT) test 3 years after birth., Results: Of the 106 enrolled women, 25 (23.6%) were H. pylori-seropositive. Maternal H. pylori seropositivity was correlated with a higher risk of developing gestational hypertension (GH) (12% vs. 1.2%, p = 0.04) and lower cord blood levels of IGF-1 (< 35 ng/ml, 70.0% vs. 40.7%, p = 0.02) and IGFBP-3 (< 1120 ng/ml, 100.0% vs. 76.3%, p = 0.02) compared with the seronegative women. No significant impacts on birth weight, childhood growth and cognitive development were found to be correlated with maternal H. pylori seropositivity during pregnancy., Conclusions: Maternal H. pylori infection during pregnancy was more likely to lead to the development of GH, but was not correlated with fetal and childhood growth and development. In addition to close monitoring of hypertension, H. pylori eradication can be considered for mothers with H. pylori infection.

Background: The outcome of methadone maintenance therapy (MMT) varies in each patient with opioid use disorder (OUD). Opioid abuse activates proinflammatory processes by increasing cytokine production and impairing neurotrophic factor expression, and possibly leads to a vicious cycle that hinders recovery. Therefore, we investigated whether markers of inflammation and neurotrophic expression correlate with the MMT outcomes in OUD patients., Method: We investigated OUD patients undergoing MMT and followed them up for 12 weeks. We measured plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, IL-1β, transforming growth factor (TGF)-β1, brain-derived neurotrophic factor (BDNF), urinary morphine tests, and plasma morphine levels at baseline and on weeks 1, 4, 8, and 12 during MMT. Multiple linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the cytokine and BDNF levels and MMT outcomes., Results: We initially enrolled 104 patients, but only 78 patients completed end-of-study assessments. Plasma levels of CRP, TGF-β1, and BDNF fell during MMT. Plasma IL-6 levels were significantly associated with plasma morphine levels (P = 0.005) and urinary morphine-positive ( + ) results (P = 0.04), and significantly associated with poor compliance (P = 0.009) and early dropout from MMT (P = 0.001). However, other cytokine and BDNF levels were not consistently associated with MMT outcomes., Conclusion: Higher IL-6 levels were associated with poor MMT outcomes. Additional studies on regulating IL-6 expression to improve treatment outcomes in OUD patients might be warranted., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We have developed a method for the highly diastereo- and enantioselective construction of 2,3-dihydrobenzofurans bearing tetrasubstituted carbon stereocenters by means of annulation reactions between carbenes and 2-iminyl- or 2-acyl-substituted phenols through catalysis by readily accessible copper(I)/bisoxazoline catalysts under mild conditions. These reactions feature a unique mechanism in which the copper catalyst serves a dual function: first it reacts with the diazo compound to generate a metal carbene, and second, upon formation of an oxonium ylide, it acts as a Lewis acid to activate the imine or ketone for diastereo- and enantioselective cyclization., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Opinion Statement: Melanoma is the deadliest form of skin cancer worldwide. The rising melanoma incidence and mortality, along with its high propensity for metastasis highlights the urgency to identify more effective therapeutic targets. Approximately, one half of advanced melanoma bears a mutation in the BRAF gene that makes BRAF as an important therapeutic target. Significant clinical benefit is associated with BRAF and MEK inhibitors (MAPKi) on targeting patients with BRAF V600 mutations. However, the frequent and rapid development of acquired resistance still is the major challenge facing the melanoma. Several mechanisms by which melanoma passes the inhibitory effects of MAPKi have been characterized and clinically translated, but additional alternations of genetic and epigenetic regulators outside of MAPK and/or AKT networks occurs in a quarter of patients with acquired MAPKi resistance. These studies implicate that targeting signaling networks external MAPK or AKT pathways is critical. In this review, we will focus on two approaches that are under evaluating for targeting melanoma: (1) against genome instability by p53 network restoration and (2) disrupt cancer proteome by chaperone inhibition.

Natural products derived from herbal medicines have become a major focus of anti-cancer drug discovery studies. Acetyl-macrocalin B (A-macB) is an ent-diterpenoid isolated from Isodon silvatica. This study aimed to examine the effect and molecular action of A-macB in esophageal squamous cell carcinoma (ESCC) and explore possible drug synergistic modalities. A-macB induced cellular reactive oxygen species (ROS) generation, initiated the p38 mitogen-activated protein kinase (MAPK) signaling pathway, and triggered the caspase-9-dependent apoptosis cascade in ESCC cells. The ROS scavenger N-acetylcysteine (NAC) and the specific p38 inhibitor SB203580 reversed the effects of A-macB on the p38 network and thus rescued ESCC cells from apoptosis. The cellular ROS increase was at least partially due to the suppression of glutathione-S-transferase P1 (GSTP1) by A-macB. A-macB also upregulated the Chk1/Chk2-Cdc25C/Cdc2/Cyclin B1 axis to induce G2/M phase arrest. The cell growth inhibition induced by A-macB was further enhanced by AZD7762, a specific Chk1/Chk2 inhibitor, with a combination index (CI) of <1. Moreover, A-macB efficiently suppressed xenograft growth without inducing significant toxicity, and AZD7762 potentiated the effects of A-macB in the suppression of tumor growth in vivo. Taken together, A-macB is a promising lead compound for ESCC and exerts synergistic anti-cancer effects with AZD7762., (Copyright © 2019. Published by Elsevier Inc.)

Owing to the beneficial properties of amniotic fluid-derived stem cells (AFSCs), including pluripotency and the lack of ethical issues associated with embryonic stem cells (ESCs), they should be a promising cell source for regenerative medicine. However, how to differentiate AFSCs into contracting cardiomyocytes has not been established. In this study, a well-established, direct cardiac differentiation protocol involving the modulation of Wnt signaling was used to differentiate Oct 3/4 + AFSCs into cardiomyocytes. By day 14 of cardiomyocyte differentiation, these AFSCs expressed cardiac-specific genes (i.e., cardiac troponin T and myosin light chain 2v) and proteins but could not spontaneously contract. Using the patch-clamp technique, we further characterized the electrophysiological properties of human ESC-derived cardiomyocytes (hESC-CMs) and differentiated AFSCs. We used different configurations to investigate membrane potentials and ion currents in differentiated AFSCs and hESC-CMs. Under cell-attached voltage- or whole-cell current-clamp modes, we recorded spontaneous action currents (ACs) or action potentials (APs) in hESC-CMs but not in differentiated AFSCs. Compared to hESC-CMs, differentiated AFSCs showed significantly diminished activity of both BK Ca and IK Ca channels, which might lead to a lack of spontaneous ACs and APs in differentiated AFSCs. These results indicated that this well-established Wnt signaling modulating cardiac differentiation protocol was insufficient to induce the differentiation of functional cardiomyocytes from Oct 3/4 + AFSCs. Therefore, AFSC may not be an ideal candidate for cardiomyocyte differentiation., Competing Interests: The authors declare no competing interests.

Background: Patients with opioid use disorder (OUD) show memory deficiencies and impaired treatment outcomes. Emerging evidence suggests that opioid abuse activates proinflammatory processes by increasing cytokine production and impairing neuroprotection, which damages the memory function in OUD patients. Therefore, we investigated whether plasma-based inflammatory and neurotrophic markers correlate with memory function in OUD patients., Method: OUD patients undergoing methadone maintenance therapy (MMT) were investigated and followed up for 12 weeks. Plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, transforming growth factor (TGF)-β1, brain-derived neurotrophic factor (BDNF) levels, and Wechsler Memory Scale-Revised (WMS-R) scores were assessed at baseline and after 12 weeks of MMT. Multiple linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between cytokines and memory performance., Results: We enrolled 89 patients at baseline; 47 patients completed the end-of-study assessments. Although Pearson correlations showed that CRP and TGF-β1 levels were significantly, negatively associated with some memory indices, the results were not significant after correction. The GEE results, controlled for several confounding factors and multiple testing, showed that changes in TNF-α levels were negatively correlated with changes in the visual memory index (P = 0.01), and that changes in IL-6 levels were negatively correlated with changes in the verbal memory index (P = 0.009)., Conclusion: Memory performance, TNF-α, and IL-6 levels in OUD patients were negative correlated. Additional studies on regulating TNF-α and IL-6 expression to improve memory function in OUD patients might be warranted., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Researchers have utilized infrared (IR) lasers as energy sources in laser therapy for curing skin diseases and skin injuries with remarkable effects. Preliminary experiments have also shown that high-intensity IR laser pulses could penetrate thick body tissues, resulting in remarkable effects for recovery from injuries in deep muscles and cartilage tissues. However, for deep-level IR laser therapy, it is unclear how much of the laser power density penetrates the body tissues at certain depths and which of the three major effects of laser irradiation, namely, laser-induced photo-chemical effect, photo-thermal effect and mechanical dragging effect, play a key role in the curing process. Thus, in this study, we developed micro-sized thin-film thermocouple (TFTC) arrays on freestanding Si 3 N 4 thin-film windows as sensors for laser power density and local temperature. These devices showed excellent linear responses in output voltage to laser power density with wavelengths in the range of 325-1064 nm, and also indicated the local temperature at the laser spot. We systematically measured the penetrating effect and thermal effect through thick porcine tissues for high-intensity IR pulses with a laser system used in clinical treatment and subtracted the attenuation parameters for the porcine skin, fat and muscle tissue from the experimental data. The results offered reliable quantitative references for safe irradiation doses of high-intensity IR laser pulses in practical laser therapy., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

To investigate whether the microRNA-144 (miR-144) had immune regulation effect on matured immune cells, we firstly used quantitative RT-PCR (qRT-PCR) to detect the expression changes of miR-144 between the matured and immature dendritic cells (DCs), macrophages, and the peripheral blood mononuclear cells (PBMCs). Then we went on inspecting the expression changes of TNF-α, IL-1β, IL-6 and IL-23 in the matured DCs treated with miR-144 mimics or inhibitors using qRT-PCR, and also performed western blot to test phosphorylation state of ERK, JNK, p38 and p65 in these cells. Next, TargetScan was conducted to forecast the target gene of miR-144, receptor activator for nuclear factor-κB ligand (RANKL), and double luciferase reporter system was applied to research their banding sites. We also determined the expression changes of RANKL in the DCs treated with miR-144 mimics or inhibitors using qRT-PCR and ELISA, respectively. The siRNA of RANKL was synthesized and transfected into DCs to inspect how the immune regulation effect of miR-144 was conducted to inhibit the expression of TNF-α using qRT-PCR, and lastly we used flow cytometry to investigate whether this effect applied to Th17 cells. As results, we found that miR-144 was down-regulated in the matured DCs, macrophages and PBMCs of liver transplantation patients, and the miR-144 mimics could inhibit the expression levels of TNF-α, IL-1β, IL-6 and IL-23 in the matured DCs. Furthermore, miR-144 interacted with RANKL at position 679-685 of RANKL 3'UTR, and suppressed the translation of RANKL mRNA to realize the negative-regulation. Besides, the silence of RANKL enhanced the suppression effect of miR-144 on TNF-α and this immune regulation effect was applied to Th17 cells, too. In conclusion, this study clearly illustrated that miR-144 could inhibit the expression of cytokine in matured immune cells through suppressing the translation of RANKL mRNA., (Copyright © 2018 Elsevier Ltd. All rights reserved.)