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Yuan Xu, Jing-Yan Wang, Yang Zou, Xue-Wei Ma, Tian Meng College of Health Industry, Sichuan Tourism University, Chengdu, Sichuan, 610100, People’s Republic of ChinaCorrespondence: Yuan Xu, Email 230973159@qq.comAbstract: Inflammatory cytokines, interleukin-36 (IL-36), IL-37, IL-38 belong to IL-1 family. The IL-36 subfamily obtains pro- and anti-inflammatory effects on various immune responses. Cytokine IL-37, has anti-inflammatory functions in immunity, and the recently identified IL-38 negatively associated with disease pathogenesis. To date, expression of IL-36, IL-37, IL-38 is reported dysregulated in osteoarthritis (OA) and rheumatoid arthritis (RA), and may be disease markers for arthritis-related diseases. Interestingly, expression of IL-38 was different either in OA patients or animal models, and expression of IL-36Ra in synovium was different in OA and RA patients. Moreover, functional studies have demonstrated significant role of these cytokines in OA and RA progress. These processes were related to immune cells and non-immune cells, where the cytokines IL-36, IL-37, IL-38 may regulate downstream signalings in the cells, and then involve in OA, RA development. In this review, we comprehensively discuss recent advancements in cytokines and the development of OA, RA. We hope that targeting these cytokines will become a potential treatment option for OA and RA in the future.Keywords: IL-36, IL-37, IL-38, osteoarthritis, rheumatoid arthritis

Tian-Jiao Xu,1,2,* Qi Wang,1,* Xiao-Wen Ma,1 Zhen Zhang,3 Wei Zhang,1 Xiao-Chang Xue,1 Cun Zhang,1 Qiang Hao,1 Wei-Na Li,1 Ying-Qi Zhang,1 Meng Li11State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, Fourth Military Medical University, Xi’an, People’s Republic of China; 2The Institute of Medicine, Qiqihar Medical University, Qiqihar, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA*These authors contributed equally to this workObjective: Thymosin beta 4 (Tβ4) is a peptide with 43 amino acids that is critical for repair and remodeling tissues on the skin, eye, heart, and neural system following injury. To fully realize its utility as a treatment for disease caused by injury, the authors constructed a cost-effective novel Tβ4 dimer and demonstrated that it was better able to accelerate tissue repair than native Tβ4.Methods: A prokaryotic vector harboring two complete Tβ4 genes with a short linker was constructed and expressed in Escherichia coli. A pilot-scale fermentation (10 L) was performed to produce engineered bacteria and the Tβ4 dimer was purified by one-step hydrophobic interaction chromatography. The activities of the Tβ4 dimer to promote endothelial cell proliferation, migration, and sprouting were assessed by tetramethylbenzidine (methylthiazol tetrazolium), trans-well, scratch, and tube formation assays. The ability to accelerate dermal healing was assessed on rats.Results: After fermentation, the Tβ4 dimer accounted for about 30% of all the bacteria proteins. The purity of the Tβ4 dimer reached 98% after hydrophobic interaction chromatography purification. An average of 562.4 mg/L Tβ4 dimer was acquired using a 10 L fermenter. In each assay, the dimeric Tβ4 exhibited enhanced activities compared with native Tβ4. Notably, the ability of the dimeric Tβ4 to promote cell migration was almost two times higher than that of Tβ4. The rate of dermal healing in the dimeric Tβ4-treated rats was approximately 1 day faster than with native Tβ4-treated rats.Conclusion: The dimeric Tβ4 exhibited enhanced activity on wound healing than native Tβ4, and the purification process was simple and cost-effective. This data could be of significant benefit for the high pain and morbidity associated with chronic wounds disease. A better strategy to develop Tβ4 as a treatment for other diseases caused by injuries such as heart attack, neurotrophic keratitis, and multiple sclerosis was also described.Keywords: thymosin beta 4, dimer, wound healing, tissue repair, peptide, genetic engineering

Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Traditional Chinese medicine can mitigate or even treat sepsis in a human system. This review examines progress on the use of TCM extracts for treating sepsis through different pharmacological action and its mechanisms. The potential targets of TCM extracts and active ingredients for the treatment of sepsis and its complications have been elucidated through molecular biology research, network pharmacology prediction, molecular docking analysis, and visualization analysis. Our aim is to provide a theoretical basis and empirical support for utilizing TCM in the treatment of sepsis and its complications while also serving as a reference for future research and development of sepsis drugs., 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 Fu, Li, Chen, Liang, Zhao, He, Ma, Yang and Wang.)

Nanozymes is a kind of nanomaterials with enzyme catalytic properties. Compared with natural enzymes, nanozymes merge the advantages of both nanomaterials and natural enzymes, which is highly important in applications such as biosensing, clinical diagnosis, and food inspection. In this study, we prepared β-MnOOH hexagonal nanoflakes with a high oxygen vacancy ratio by utilizing SeO 2 as a sacrificial agent. The defect-rich MnOOH hexagonal nanoflakes demonstrated excellent oxidase-like activity, catalyzing the oxidation substrate in the presence of O 2 , thereby rapidly triggering a color reaction. Consequently, a colorimetric sensing platform was constructed to assess the total antioxidant capacity in commercial beverages. The strategy of introducing defects in situ holds great significance for the synthesis of a series of high-performance metal oxide nanozymes, driving the development of faster and more efficient biosensing and analysis methods., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, author-ship, and/or publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Noninvasive measurement of myocardial work (MW) incorporates left ventricular (LV) pressure, and, therefore, allows correction of global longitudinal strain for changing afterload conditions. We sought to investigate MW as a tool to detect early signs of LV dysfunction in primary systemic hypertension patients, particularly with different predictive indices., Methods and Results: None left ventricular hypertrophy (NLVH) and left ventricular hypertrophy (LVH) patients established were all primary systemic hypertension with preserved ejection fraction. Forty in NLVH and forty in LVH according to left ventricular end-diastolic mass index (LVEDmassI) were prospectively enrolled. The following indices of MW were assessed: global work index, global constructive work, global wasted work (GWW), and global work efficiency (GWE). Both global work index ( P =0.348) and global constructive work ( P =0.225) were increased in NLVH and decreased in LVH, and GWW ( P <0.001) was increased significantly in NLVH and increased more in LVH, while GWE ( P <0.001) was decreased significantly in NLVH and decreased more in LVH. The clinical utility of GWW (95% CI: 0.802-0.951) and GWE (95% CI: 0.811-0.950) were verified by receiver-operating characteristic curve analysis showing larger net benefits as evaluated with LVH and control comparisons. In multivariate linear regression analysis, 4-dimenaional LVEDmassI was independently associated with GWE ( P =0.018) in systemic hypertension patients. Assessment of intraobserver and interobserver variability in the MW echocardiographic data documented good interclass correlation coefficients (all >0.85)., Conclusion: GWW and GWE derived from MW are more accurate, sensitive, and reproducible predictors to detect early LV dysfunction in primary systemic hypertension patients, especially in distinguishing the potential functional abnormality of NLVH and LVH, even though the ejection fraction is preserved., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective To analyze the diagnostic values of H 2 FPEF and HFA-PEFF scores for heart failure with preserved ejection fraction (HFpEF) and HFpEF complicated with atrial fibrillation (HFpEF-AF) in Chinese patients and explore the related factors. Methods A cross-sectional study was conducted.A total of 835 consecutive HFpEF patients treated in the Department of Geriatric Cardiology,the First Hospital of Lanzhou University from 2009 to 2020 were selected and assigned to a HFpEF-AF group ( n =267) and a HFpEF group ( n =568) according to the presence of AF or not.HFA-PEFF and H 2 FPEF scores were used for retrospective diagnosis and the diagnostic consistency of the two scores was assessed.One hundred and thirty-six healthy volunteers with age and sex matching the patients during the same period were selected as healthy controls.The receiver operating characteristic (ROC) curves were established for H 2 FPEF and HFA-PEFF scores in diagnosing HFpEF-AF and HFpEF,on the basis of which the diagnostic performance of the two scores was evaluated. Results There was no difference in the HFA-PEFF score between the two groups ( P =0.070).However,the HFpEF-AF group had higher mean H 2 FPEF score and higher proportion of patients with the score no less than 6 than the HFpEF group ( P <0.001).According to the ROC curves,HFA-PEFF and H 2 FPEF scores demonstrated high performance in diagnosing all HFpEF patients,with the area under the curve (AUC) of 0.892 and 0.922 and the optimal cut-offs of 4 and 4,respectively.The HFA-PEFF score showed similar performance in diagnosing HFpEF and HFpEF-AF,with the AUC of 0.899 and 0.911,respectively.The H 2 FPEF score had higher performance in diagnosing HFpEF-AF (AUC of approximately 1.000) and low performance in diagnosing HFpEF (AUC of 0.885). Conclusions The HFA-PEFF score is applicable in the diagnosis of both HFpEF and HFpEF-AF.The H 2 FPEF score may underestimate HFpEF in Chinese patients,and its applicability in the Chinese patients with HFpEF alone remains to be investigated.

Osteoarthritis (OA) is a chronic, degenerative, and age-related disease. It is characterized by chronic inflammation, progressive articular cartilage destruction, and subchondral bone sclerosis. The current effective treatment for OA is limited. Hydrogel is a kind of unique carrier with well-known biocompatibility, softness, and high water content among various biomaterials. Hydrogels are developed for different biomedical applications, for instance, drug delivery, and tissue engineering. To date, a variety of hydrogels-based therapies have been used in OA patients or animal models. In this review, we comprehensively summarized the potential role of hydrogels in chondrocytes proliferation, apoptosis, and inflammatory component production and discussed the impact of hydrogels on OA development. The collection of this information will help better understand the present progress of hydrogels in OA., (© 2023 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: To investigate the effect of Diclofenac sodium sustained-release capsules combined with function training on functional recovery and Visual Analog Scale (VAS) score after surgery for ankle fractures., Patients and Methods: The study included 88 patients with ankle fractures who were surgically treated at our institution between October 2019 and October 2021. The individuals were randomized into experimental and control groups, with 44 patients in each group. Following their hospitalization, all patients had surgical therapy. After surgery, patients in the control group received conventional analgesics together with function training, whereas those in the experimental group received Diclofenac sodium sustained-release capsules along with function training. The efficacy of the post-surgical treatment in the two groups was then evaluated using functional recovery and VAS scores., Results: There was no significant difference in the VAS score between the two groups before intervention (p>0.05). After treatment, both groups experienced pain relief, with the VAS score of the experimental group being significantly lower than the control group (p<0.05). The number of patients in the experimental group who fully and partially complied with the study was 19 and 24, respectively, significantly higher than that of 15 and 20 in the control group. Only 1 patient in the experimental group was non-compliant, compared to 9 in the control group. The total compliance rate in the experimental group was 97.73%, much higher than that of 79.55% in the control group (p<0.05). Before the intervention, there was no significant difference in the range of active ankle motion between the two groups (p>0.05). After treatment, there was an improvement in the range of active motion of the ankle in patients from both groups., Conclusions: After ankle fracture surgery, using Diclofenac sodium sustained-release capsules in conjunction with function training successfully lowers postoperative pain. It also maintains emotional stability and ensures sleep, factors which are helpful in improving patient compliance to treatment and promoting functional recovery of the ankle. The clinical value of this treatment regimen is certain, and it deserves more widespread application.

Background: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF., Methods: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes., Results: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system., Conclusions: In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models., Competing Interests: Jing LI reported receiving research grants, through Fuwai Hospital, from the Chinese government for work to improve the management of hypertension and blood lipids, to improve care quality and patient out-comes of cardiovascular disease, and to improve care for COVID-19 infection; receiving research agreements, through the National Center for Cardiovascular Diseases and Fuwai Hospital, from Amgen for a multicenter clinical trial assessing the efficacy and safety of omecamtiv mecarbil and for dyslipidemic patient registration; receiving a research agreement, through Fuwai Hospital, from Sanofi for a multicenter clinical trial on the effects of sotagliflozin; receiving a research agreement, through Fuwai Hospital, with the University of Oxford for a multicenter clinical trial of empagliflozin; receiving a research agreement, through the National Center for Cardiovascular Diseases, from AstraZeneca for clinical research methods training outside the submitted work; and receiving a research agreement, through the National Center for Cardiovascular Diseases, from Lilly for physician training outside the submitted work. Impedance cardiography devices (CHM T3002/P3005 HDpro) were manufactured and provided by Shandong Baolihao Medical Appliances, Ltd. The company did not participate in the design and conduct the study; collection, management, analysis, and interpretation of the data; or preparation of the manu script. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 JGC All rights reserved; www.jgc301.com.)

Objective: To investigate the correlation between different clinical features and live birth in patients with severe late-onset ovarian hyperstimulation syndrome (OHSS) after in vitro fertilization-embryo transfer (IVF-ET). Methods: The clinical information of 330 patients who were pregnant after IVF-ET and referred to medical treatments diagnosed as late-onset severe OHSS in Peking University Third Hospital from January 2016 to December 2020 was retrospectively analyzed. The patients were divided into live birth achieved group ( n =287) and non-live birth achieved group ( n =43) according to pregnancy outcomes, and live birth achieved group was further divided into two subgroups, full-term birth group ( n =222) and early-term birth group ( n =65) according to gestational week at delivery for better analysis. Single factor and multi-factor analysis were utilized to clarify the influencing factors of both live birth and early-term birth. Results: Among all the patients who received IVF-ET, the incidence of severe OHSS was 0.67% (673/100 758). Among 330 severe late-onset OHSS patients, 42.4% (140/330) had pleural effusion, the incidence of abnormal liver function was 69.4% (229/330), and the live birth rate was 87.0% (287/330). Among the 287 patients who achieved live birth, 55.4% (159/287) had no pleural effusion, 18.5% (53/287) had a small amount of pleural effusion, and 26.1% (75/287) had medium or massive pleural effusion; in the non-live birth achieved group, there were more patients without pleural effusion and less patients with a small amount of pleural effusion; the difference was statistically significant ( χ 2 =6.213, P =0.045). The rate of selective fetal reduction in live birth achieved group was 16.0% (46/287), which was significantly higher than that in the non-live birth achieved group, which was 2.3% (1/43; χ 2 =5.749, P =0.017). Multivariate logistic regression analysis revealed that moderately abnormal liver function was an independent risk factor for live birth ( OR =3.15, 95% CI : 1.60-6.19), while selective fetal reduction was an independent protective factor for live birth ( OR =0.13, 95% CI : 0.02-0.96). Additionally, subgroup analysis suggested that twin birth was an independent risk factor for preterm birth ( OR =8.54, 95% CI : 4.31-16.91). Conclusions: Moderate hepatic dysfunction may be associated with adverse pregnancy outcomes in patients with severe late-onset OHSS. Selective fetal reduction and singleton pregnancy are recommended to ameliorate live birth rate, full-term delivery rate, also the maternal and neonatal prognosis for patients with multiple pregnancies.

In 2016, two adult male sperm whales beached off of Yangkou Port in Nantong City, Jiangsu Province, China. The local government planned to preserve them as specimens, one was entrusted to Dalian Hoffen Biological Co., Ltd., and thus became the first sperm whale to be preserved by plastination. The other sperm whale was preserved in Nantong by the traditional stripping method (The skin was preserved, and then the prosthesis was filled into the skin to preserve the specimens. The material of the prosthesis was polyurethane. The outline of the animal was sculpted by suturing the skin like a bag and filling it with polyurethane). Plastination of such a large marine mammal allowed us to view the mutual adaptations of its internal structure to its specific living environment and daily habits. This sperm whale is the largest specimen in the world and this is the first time a sperm whale has been preserved using the plastination method. The plastination process also provides a method for studying the anatomy of large marine mammals for humans to understand deep-sea organisms at close contact and visual level. The plastination of this sperm whale promises to be a world class resource holding tremendous scientific, educational, and artistic value., (© 2021 Anatomical Society.)

Background and Aims: Despite the remarkable progress of metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named non-alcoholic fatty liver disease (NAFLD), the disease remains poorly improved. Since increased oxidative stress and inflammation contribute to the initiation and progression of fatty liver disorders, vitamin C (VC), an antioxidant agent, might be a suitable treatment option for MAFLD. However, the lack of clinically confirmed benefits makes clinicians challenging to recommend antioxidant supplements for MAFLD individuals., Methods: Herein, the nationally representative National Health and Nutrition Examination Survey 2017-2018 data were collected to evaluate the potential association between the serum VC levels with the risk of different categories of NALFD and the newly proposed MAFLD terminology. Hepatic steatosis was defined as controlled attenuated parameter scores ≥ 263 dB/m, whereas liver fibrosis (LF) status was defined as F0-F4, with the cutoff values of median liver stiffness being 6.3, 8.3, 10.5, and 12.5 (KPa), respectively. A cross-sectional analysis was performed to calculate the odds rate and determine the potential beneficial effects of VC., Results: A total of 4,494 participants aged more than 18 years and conducted transient elastography examinations were included. Our findings demonstrated that participants with increased serum VC status were more likely to be female predominant, more educated, and moderate drinkers. Interestingly, female participants tended to have a lower prevalence of NAFLD, MAFLD, LF, and liver cirrhosis (LC) after stratification by gender. Moreover, our results revealed that participants from the quartile three group (quartile 3: 50.5-67.0 μmol/L) experienced a slightly lower risk of MAFLD than the risk of NAFLD. Of note, the serum concentration of VC (quartile 2: 30.9-50.5 μmol/L) inversely associated with LF and LC was lower than the serum VC level (quartile 3) associated with NAFLD and MAFLD. Notably, individuals from the quartile 3 group experienced a statistically significant 32.5, 42.0, 45.7, and 71% decrease in risk of NAFLD, MAFLD, LF, and LC, respectively., Conclusion: In summary, our findings suggested an inverse association between serum VC levels and NAFLD, MAFLD, LF, or LC. Additionally, adjustment of VC supplementation according to age, gender, and ethnicity may be a promising candidate for these diseases., 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 Xie, Li, Tan, Yang, Ma, Li, Wang, Shang and Chen.)

Objective: The objective of this study was to describe the different components of left atrial (LA) dysfunction predictors in nonobstructive and occult obstructive hypertrophy cardiomyopathy (HCM) patients especially with preserved left ventricular (LV) ejection fraction, particularly using LA 4-dimensional (D) longitudinal and circumferential strains., Methods: Twenty-eight nonobstructive HCM patients and 30 occult obstructive HCM patients according to LV outflow tract gradient at rest and after exercise were prospectively enrolled. 4D echocardiographic evaluation was performed in 58 HCM patients, both nonobstructive and occult obstructive, and 38 control subjects. LA reservoir, conduit, contractile functions were performed by 4D volume-strain with volumes and longitudinal, circumferential strains., Results: Optimal correlation coefficients obtained between LV 4D mass (index) and LA 4D longitudinal/circumferential strain (r=-0.860 to 0.518, all P<0.001). Both nonobstructive and occult obstructive HCM patients had increased volumes and significantly decreased longitudinal, circumferential strain values with lower reservoir, conduit, contractile functions than the controls (all P<0.001). Occult obstructive HCM patients presented incremented volumes compared with nonobstructive ones (P<0.001 to 0.003). Lower conduit function and higher contractile function indicated with lower reservoir function revealed by circumferential strain in occult obstructive HCM patients than nonobstructive ones (P<0.001 to 0.017). Interclass correlation coefficients of intraobserver and interobserver in the LV and LA 4D value evaluations were >0.75 and >0.85, respectively., Conclusions: LA volumes were significantly increased and LA reservoir, conduit, and contractile functions were significantly impaired in HCM patients. Furthermore, different performances of LA functional analyses in nonobstruction and occult obstruction patients with 4D volume-strain echocardiography may facilitate the recognition of subtle LA dysfunctional differentiation in HCM patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To analyze the clinical characteristics of aldosterone-producing adenoma (APA) subtypes in primary aldosteronism (PA) and the application value of captopril challenge test (CCT) in adenomas. And to find out the clinically specific non-invasive index for identifying APA subtypes from PA., Methods: The clinical data of hospitalized patients with hypertension were retrospectively collected. All the patients were conducted with the CCT and 90 patients with PA were confirmed. Among them, 34 patients were confirmed to have APA by surgery. The clinical indicators of the two groups of patients including plasma aldosterone concentration (PAC), aldosterone inhibition rate (%), and aldosterone to renin ratio (ARR) before and after the CCT were compared, the receiver operating characteristic (ROC) curves for the relevant indicators before and after the CCT drawn, and the areas under the curve (AUC) compared. The ROC curves were used to analyze the efficiency of the different CCT diagnostic criteria for diagnosing APA., Results: Compared with the PA group, the duration of hypertension was shorter, the incidence of hypokalemia was higher, and the average serum potassium level was lower when APA was diagnosed. There were no significant differences in blood pressure level, gender, serum sodium and body mass index between the two groups. Compared with PA population, APA group had higher PAC and ARR whether before or after the CCT, but lower plasma renin concentration (PRC). In APA patients, the mean degree of PAC declined after CCT was approximately 5.7%, but 5% with that of PA. As for diagnosing, ARR before or after CCT had diagnostic value for APA, in which the ARR cut-off point was 7.12, which yielded a sensitivity and specificity of 35.85% and 77.78%. The cut-off point of ARR after CCT was 4.23, with a sensitivity of 71.43% and specificity of 62.22%. For the diagnosis, the ARR before and after CCT were of no significant difference. However, the diagnostic specificity of ARR>7.12 combined with hypokalemia was up to 80%., Conclusion: ARR before or after CCT have clinical value for the diagnosis of APA from PA, when combined with hypokalemia yielded high specificity.

Background and Aims: Cholecystectomy is the "gold standard" for treating diseases of the gallbladder. In addition, non-alcoholic fatty liver disease (NAFLD), liver fibrosis or cirrhosis, are major causes of morbidity and mortality across the world. However, the association between cholecystectomy and these diseases is still unclear. We assessed the association among US adults and examined the possible risk factors. Methods: This cross-sectional study used data from 2017 to 2018 National Health and Nutrition Examination Survey, a population-based nationally representative sample of US. Liver fibrosis and cirrhosis were defined by median stiffness, which was assessed by transient elastography. Furthermore, patients who had undergone cholecystectomy were identified based on the questionnaire. In addition, Propensity Score Matching (PSM, 1:1) was performed based on gender, age, body mass index (BMI) and diabetes. Results: Of the 4,497 included participants, cholecystectomy was associated with 60.0% higher risk of liver fibrosis (OR:1.600;95% CI:1.278-2.002), and 73.3% higher risk of liver cirrhosis (OR:1.733, 95% CI:1.076-2.792). After PSM based on age, gender, BMI group and history of diabetes, cholecystectomy was associated with 139.3% higher risk of liver fibrosis (OR: 2.393;95% CI: 1.738-3.297), and 228.7% higher risk of liver cirrhosis (OR: 3.287, 95% CI: 1.496-7.218). Conclusions: The present study showed that cholecystectomy is positively associated with liver fibrosis and cirrhosis in US adults. The discovery of these risk factors therefore provides new insights on the prevention of NAFLD, liver fibrosis, and cirrhosis., 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 Xie, Li, Tan, Yang, Ma, Li, Wang, Shang and Chen.)

Objective: At conditionally automated driving, the driver can temporarily engage in non-driving related tasks (NDRTs). However, they must safely take over control when the automated driving system reaches its operation limit. Thus, understanding the effects of the NDRTs on driver take-over performance is essential. The present work investigates the effects of various NDRTs on motor readiness in take-over scenarios during conditionally automated driving., Methods: Three driving simulator studies were conducted. 48, 49, and 22 participants were recruited in three experiments, respectively. The participants were distracted by different NDRTs (everyday task in Experiment 1, arrow task in Experiment 2, and SuRT in Experiment 3) on a tablet mounted in the vehicle. The everyday task included reading the news and watching a video, and the arrow task included a set of arrow matrices presented to the participants in sequence. The time budgets in Experiment 1 included 3 s, 4 s, and 5 s, and the time budgets in Experiment 2 and 3 included 5 s and 7 s. A take-over request (TOR) warning was issued in the automated driving condition when the participants encountered a broken-down car in front. The participants must regain control of the vehicle with the given time budget. The hands-on time was evaluated, measuring the time from the TOR until the hands touch the steering wheel., Results: The task (arrow task and SuRT), time budget (5 s and 7 s), and gender did not affect the hands-on time. However, the hands-on time for the drivers with the everyday task was significantly shorter than that for the drivers with the arrow task in the 5 s time budget., Conclusions: In conditionally automated driving, the arrow task and SuRT imposed a similar workload on readiness to take over control. Compared to the everyday task, the engagement in the arrow tasks consumed more workload on readiness to take over control.

Objective: To understand the epidemiological characteristics of imported COVID-19 cases in Guangzhou and provide scientific basis for the prevention and control of the disease. Methods: The data of imported COVID-19 in Guangzhou reported as of April 1, 2020 were collected from National Notifiable Disease Report System of China. The software Excel 2010 and SPSS 19.0 were applied for data cleaning and statistical analysis. Results: As of April 1, 2020, a total of 103 imported COVID-19 cases had been reported in Guangzhou, in which 92 were confirmed cases and 11 were asymptomatic infection cases. The number of the confirmed imported cases accounted for 11.4 % (92/806) in of the total in China at the same time. The male to female ratio of the cases was 1.58∶1 (63∶40). The median age of the cases was 31 years ( P(25) - P(75) :22-40 years), range of age was 11-63 years. The main occupational distributions of the cases were business services (41/103, 39.8 % ) and students (36/103, 35.0 % ). The imported cases whose destinations were 19 provinces and municipalities rather than Guangdong after entering the country accounted for 43.7 % . The main source countries of infections were the United Kingdom (27/103, 26.2 % ), the Philippines (13/103, 12.6 % ), the United States (13/103, 12.6 % ) and Nigeria (7/103, 6.8 % ). There were 34 inbound flights from which the imported COVID-19 cases were detected, in which 10 flights (10/34, 29.4 % ) were found to carry more than 3 cases, with an average voyage time of (11.14±0.53) hours. A total of 29 imported cases(28.2 % ) showed symptoms before entering the country, and 65 cases (63.1 % ) had been isolated before the onset of the disease. The mean free activity time of the isolated cases after the onset was (6.76±0.79) days. The average number of the imported cases' close contacts was 53. There were 13 clusters of COVID-19 caused by the imported cases, involving 36 cases (including 1 imported associated case). Conclusions: The sources of the imported COVID-19 cases in Guangzhou were widely distributed, and no cases had been found to be infected on the flights. In the early stage of the imported epidemic, there was high risk for the spread of the epidemic. Strengthened prevention and control of imported COVID-19 effectively reduced the of transmission risk of COVID-19 in communities.

β-delayed one-proton emissions of ^{22}Si, the lightest nucleus with an isospin projection T&#95;{z}=-3, are studied with a silicon array surrounded by high-purity germanium detectors. Properties of β-decay branches and the reduced transition probabilities for the transitions to the low-lying states of ^{22}Al are determined. Compared to the mirror β decay of ^{22}O, the largest value of mirror asymmetry in low-lying states by far, with δ=209(96), is found in the transition to the first 1^{+} excited state. Shell-model calculation with isospin-nonconserving forces, including the T=1, J=2, 3 interaction related to the s&#95;{1/2} orbit that introduces explicitly the isospin-symmetry breaking force and describes the loosely bound nature of the wave functions of the s&#95;{1/2} orbit, can reproduce the observed data well and consistently explain the observation that a large δ value occurs for the first but not for the second 1^{+} excited state of ^{22}Al. Our results, while supporting the proton-halo structure in ^{22}Al, might provide another means to identify halo nuclei.

Temporal transcriptome analysis combined with targeted metabolomics was employed to investigate the mechanisms of high sugar accumulation in fruit pulp of two contrasting mango cultivars. Ten sugar metabolites were identified in mango pulp with the most dominant being d-glucose. Analysis of the gene expression patterns revealed that the high-sugar cultivar prioritized the conversion of sucrose to d-glucose by up-regulating invertases and β-glucosidases and increased other genes directly contributing to the synthesis of sucrose and d-glucose. In contrast, it repressed the expression of genes converting sucrose, d-glucose and other sugars into intermediates compounds for downstream processes. It also strongly increased the expression of alpha-amylases which may promote high degradation of starch into d-glucose. Besides, ¾ of the sugar transporters was strongly up-regulated, indicative of their preponderant role in sugar accumulation in mango fruit. Overall, this study provides a good insight into the regulation pattern of high sugar accumulation in mango pulp., (Copyright © 2020. Published by Elsevier Inc.)

Background: We try to investigate whether the values of three-dimensional principal longitudinal strain present differently between the left and right ventricles in patients with long-time follow-ups after heart transplantation (HTx)., Methods and Results: Transthoracic echocardiography with three-dimensional speckle tracking was performed at one-, five- and ten-year follow-ups in 62 "healthy" HTx patients together with routine echocardiographic evaluation in 32 control group (CG) individuals. Longitudinal strain was applied in all subjects assessing without myocardium wall motion abnormality. Firstly, left ventricular ejection fraction preserved in HTx and had no significant difference in comparison with the controls (p > .05). 3D measurement showed obvious reduction in global (%: CG: -20.5 ± 3.5 vs. HT1y: -13.7 ± 4.6, HT5y: -14.4 ± 4.5, HT10y: -14.6 ± 4.7. p < .01) and horizontal segmental (basal, mid, apical, CG vs. HTx: all p < .01) strain values of the left compared HTx with control subjects. Secondly, tissue Doppler imaging s' velocity and tricuspid annular plane systolic excursion reduced in HTx as compared to the controls in right ventricle (p < .01). Longitudinal strain presented a more distinctive reduction in global (%: CG: -24.5 ± 4.6 vs. HT1y:-14.8 ± 7.5, HT5y: -15.5 ± 6.4, HT10y: -15.9 ± 6.8. p < .01) and horizontal segmental (basal, mid, apical, CG vs. HTx: all p < .01) average values of the right compared HTx with control subjects. Thirdly, there weren't any significant changes between one-, five- and ten-year of all the values with HTx inter-group comparison in both the left and right ventricles (p > .05). Fourthly, the global and segmental strain of the right ventricle decreased more than that of the left ventricle in all HTx groups, with the global decreased differentiation rates of 7%, 7%, 6%, respectively., Conclusions: Compared HTx with control subjects in both ventricles, conventional evaluation showed preserved or decreased functions in the left and right separately. Myocardial function evaluating by 3D longitudinal strain reduced after HTx, but the deformation of the right ventricle reduced more than those of the left ventricle. Additionally, 3D strain values almost remained with stable decreased differentiation rates during the long-time follow-ups., (© 2020 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Objective: To observe the clinical efficacy and safety of electroacupuncture (EA) at Neimadian-point for cancer pain., Methods: A total of 140 cancer patients with pain were randomly divided into EA and control groups, with 70 cases in each group. The patients of the EA group received EA at Neimadian-point plus analgesia pump (all prepared with normal saline). The patients of the control group were treated by Sufentanil patient-controlled intravenous analgesia plus sham EA (without stimulation). The treatment was conducted once daily for two days at 8 o'clock every morning. Respectively, in 1 h before treatment (T0), 1 h (T1), 8 h (T2), 24 h (T3) after treatment of the first day, 1 h (T4), 8 h (T5), 24 h (T6) after treatment of the second day, the visual analogue scale (VAS) score of pain, and the plasma levels of norepinephrine, 5-HT, leucine enkephalin, β-endorphin and dynorphin A1-13 were tested. The security level (1-4 grade) was assessed during the treatment., Results: Compared with their own pre-treatment, in T1 to T6, the VAS scores, and the contents of plasma norepinephrine and 5-HT obviously decreased in both groups （ P <0.05）, and the contents of leucine enkephalin, β-endorphin and dynorphin A1-13 all increased ( P <0.05) in the EA group. The analgesia effects were significantly higher in the EA group than in the control group in T1, T2, T4 and T5 ( P <0.05, P <0.01). The therapeutic effect of EA at Neimadian-point was significantly superior to that of the Sufentanil in down-regulating plasma norepinephrine and 5-HT levels, and in up-regulating leucine enkephalin, β-endorphin and dynorphin A1-13 levels ( P <0.05, P <0.01)., Conclusion: EA at Neimadian-point can effectively relieve the pain of cancer patients and improve their quality of daily life.

Objective: To analyze the correlation between climatic factors and the incidence of varicella in Guangzhou, and improve the prevention measures about public health., Methods: Data for daily climatic variables and varicella incidence from 2006 to 2018 in Guangzhou were collected from the Guangzhou Meteorological Bureau and the National Notifiable Disease Report System. Distributed lag nonlinear models were applied to evaluate the association between climatic factors and varicella incidence., Results: The nonlinear effects of meteorological factors were observed. At lag day21，when the mean temperature was 31.8 °C, the relative risk was the highest as 1.11 (95% CI: 1.07-1.16). When the diurnal temperature range was 24.0 °C at lag day 20, the highest RR was 1.11 (95% CI: 1.05-1.17). For rainfall, the highest RR was 1.09 (95% CI: 1.01-1.19) at lag day 21，when the aggregate rainfall was 160 mm. When air pressure was 1028 hPa, the highest RR was 1.08 (95% CI: 1.04-1.13) at lag day 21. When wind speed was 0.7 m/s, the highest RR was 1.07 (95% CI: 1.04-1.11) at lag day 7. When the hours of sunshine were 9.0 h at lag day 21, the RR was highest as 1.04 (95% CI: 1.02-1.05). Aggregate rainfall, air pressure, and sunshine hours were positively correlated with the incidence of varicella, which was inconsistent with the wind velocity. Mean temperature showed a reverse U-shape curve relationship with varicella, while the diurnal temperature range showed a binomial distribution curve. The extreme effect of climatic factors on the varicella cases was statistically significant, apart from the extremely low effect of rainfall., Conclusion: Our preliminary results offered fundamental knowledge which might be benefit to give an insight into epidemic trends of varicella and develop an early warning system. We could use our findings about influential factors to strengthen the intervention and prevention of varicella., 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 Elsevier B.V. All rights reserved.)

This study aimed to evaluate jaundice outcomes of low-birthweight premature infants commenced on earlier versus later nutrient supplementation (80 mL/kg/day vs. 160 mL/kg/day; total fluid intake, F80 vs. F160). Demographics, feeding regimens, and clinical outcomes data were collected. Infant and maternal characteristics were similar. Earlier nutrient supplementation was associated with multiple improved jaundice outcomes: total (TSBR), unconjugated and conjugated (CSBR) serum bilirubin values (196 ± 46 vs. 228 ± 52, 184 ± 44 vs. 212 ± 50, 12 ± 4 vs. 16 ± 5, respectively, all p < 0.001); phototherapy (39% vs. 64%, p < 0.0001). % CSBR/TSBR ratio was similar between groups. For those on phototherapy, duration and median irradiance were similar. F80 infants experienced reduced: feeding intolerance (26.0% vs. 45.2%, p = 0.007); length of stay (16.0 ± 0.64 vs. 18.8 ± 0.74 days, p = 0.03), maximum weight loss as % birth weight (5% vs. 6%, p = 0.03); decrease in weight Z-score at 10 days (-0.70 ± 0.03 vs. -0.79 ± 0.03, p = 0.01). F80 infants regained birthweight earlier (10.0 ± 0.3 days vs. 11.5 ± 0.3 days, p < 0.0001) and had no differences in adverse clinical outcomes. We speculate that earlier nutrient supplementation improved jaundice outcomes due to enhanced excretion/elimination of bilirubin.

Objective: We try to investigate whether the values of longitudinal strain present differences between the left and right ventricles in long-time follow-ups after heart transplantation (HTx) with dynamic changes in function., Methods and Results: Follow-up transthoracic echocardiography was performed in 1- and 3-month and 1- and 5-year follow-ups in 50 "healthy" HTx patients and compared with 26 control subjects. The left ventricle with preserved ejection fraction evaluated by biplane Simpson (control group [CG] vs HT; P > .05) had an obvious reduction in global (CG: -20.49 ± 2.38 vs heart transplant 1 month [HT1m]: -13.06 ± 2.86, heart transplant 3 month [HT3m]: -13.61 ± 2.61, heart transplant 1 year [HT1y]: -13.69 ± 4.56, heart transplant 5 year [HT5y]: -14.41 ± 4.54; P < .001) and horizontal segmental (basal, mid, apical) (P < .001) together with chamber segmental (apical 4-chamber, apical 3-chamber, apical 2-chamber) (P < .001) average strain values. The right ventricle with reduced ventricular function measured by tissue Doppler imaging S' and tricuspid annular plane systolic excursion had a more distinctive reduction in global (CG: -24.53 ± 4.20 vs HT1m: -12.94 ± 5.03, HT3m: -13.68 ± 4.35, HT1y: -14.95 ± 7.50, HT5y: -15.20 ± 6.15; P < .001) with segmental lateral (P < .001) strain values. There were not any significant changes between 1- and 3-month follow-ups of all the values (P > .05). But it could be seen that values increased in 1- and 5-year follow-ups compared with the baseline of 1- and 3-month follow-ups (P < .05). The global and segmental strain of the right ventricle decreased more than that of the left ventricle in all HTx groups, and the strain values were decreased in the HTx groups compared with the CG, with the global decreased change rates being 11%, 10%, 6%, and 8%, respectively., Conclusions: The strain values decreased after HTx and almost remained stable in the long-time follow-ups. Compared with the CG in both ventricles, they were with preserved or reduced functions. In addition, the deformation values of the right ventricle decreased more than those of the left., (© 2020 Wiley Periodicals, Inc.)

The objective of this study was to evaluate the effects of dietary linoleic acid (LA) on growth performance, antioxidant capacity, and lipid metabolism in pigeon squabs by supplementing LA in their parental diets. A completely randomized design that consisted of a control group, 1% dietary LA addition group (LA1%), 2% dietary LA addition group (LA2%), and 4% dietary LA addition group (LA4%) was used. Six squabs from each treatment were randomly sampled at the day of hatch and days 7, 14, and 21 after hatch. The results showed that parental dietary LA had no significant influence (P > 0.05) on body weight (BW) gain or relative organ weights (% of BW) in squabs. The activities of superoxide dismutase, catalase, and glutathione peroxidase in the LA1% were significantly increased (P < 0.05) compared with those in the control group. The malondialdehyde content in the LA1% was significantly lower (P < 0.05) than that in the control group. The levels of serum triglyceride in the LA1% and LA2% were significantly decreased (P < 0.05) compared with those in the control group, whereas the serum high-density lipoprotein cholesterol level in the LA1% and LA2% and the free fatty acid level in the LA4% were significantly higher (P < 0.05) than those of the control group. The activities of lipoprotein lipase, hepatic lipase, and hormone-sensitive lipase in the LA1% were significantly higher (P < 0.05) than those in the control group. The 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in the LA1% and the hormone-sensitive lipase activity in the LA4% were significantly decreased (P < 0.05) compared with those in the control group. The mRNA expression of carnitine palmitoyltransferase 1, acyl-CoA 1, and peroxisome proliferator-activated receptor α was significantly upregulated (P < 0.05) in the LA1% compared with that in the control group. The Oil Red O staining area in the LA1% and LA2% was significantly reduced compared with that in the control group. The results indicated that although supplemental LA had negligible effects on growth and development in pigeon squabs, parental dietary LA at a concentration of 1% could have beneficial effects on maintaining squabs healthy as reflected by improved antioxidant capacity and lipid metabolism., (Copyright © 2019. Published by Elsevier Inc.)

Background: Infectious and non-infectious risks associated with international travel can be reduced with adherence to pre-travel advice from practitioners trained in travel medicine., Methods: A prospective cohort study was conducted in a tertiary care children's hospital to assess adherence to malaria chemoprophylaxis, safe water and food consumption, mosquito bite protection, motor vehicle safety and travel vaccines using structured questionnaires. High risk groups assessed included child travelers and those visiting friends and relatives (VFRs)., Results: In total, 290 participants (133 children and 157 adults) were enrolled and completed at least one study questionnaire. In general, with the exception of vaccines, adherence to recommendations was sub-optimal. Among children and adults, adherence to malaria prophylaxis recommendations was lower in VFRs than in non-VFRs. The proportion of children VFRs (cVFRs) and adult VFRs (aVFRs) who adhered to the following recommendations were malaria chemoprophylaxis (47%, 33%), safe water (71%, 74%) and food recommendations (18%, 6%), insect bite avoidance (21%, 12%), and motor vehicle safety (13%, 11%) respectively. Adherence to recommended vaccines uptake was greater than 90% in all groups., Conclusion: With the exception of vaccine uptake, sub-optimal adherence levels to travel recommendations was identified in all groups, and in particular VFRs, highlighting the need for proactive discussions around barriers to adherence., Competing Interests: Declaration of competing interests The authors state they have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The broad spectrum of intellectual disability (ID) patients' clinical manifestations, the heterogeneity of ID genetic variation, and the diversity of the phenotypic variation represent major challenges for ID diagnosis. By exploiting a manually curated systematic phenotyping cohort of 3803 patients harboring ID, we identified 704 pathogenic genes, 3848 pathogenic sites, and 2075 standard phenotypes for underlying molecular perturbations and their phenotypic impact. We found the positive correlation between the number of phenotypes and that of patients that revealed their extreme heterogeneities, and the relative contribution of multiple determinants to the heterogeneity of ID phenotypes. Nevertheless, despite the extreme heterogeneity in phenotypes, the ID genes had a specific bias of mutation types, and the top 44 genes that ranked by the number of patients accounted for 39.9% of total patients. More interesting, enriched co-occurrent phenotypes and co-occurrent phenotype networks for each gene had the potential for prioritizing ID genes, further exhibited the convergences of ID phenotypes. Then we established a predictor called IDpred using machine learning methods for ID pathogenic genes prediction. Using10-fold cross-validation, our evaluation shows remarkable AUC values for IDpred (auc = 0.978), demonstrating the robustness and reliability of our tool. Besides, we built the most comprehensive database of ID phenotyped cohort to date: IDminer http://218.4.234.74:3100/IDminer/, which included the curated ID data and integrated IDpred tool for both clinical and experimental researchers. The IDminer serves as an important resource and user-friendly interface to help researchers investigate ID data, and provide important implications for the diagnosis and pathogenesis of developmental disorders of cognition., (Copyright © 2020 Wang, Zhu, Ma, Yang, Xu, Yang, Yang, Peng, Zhang, Liang, Zhu, Jiang, Zhang and Feng.)

Objective: The purpose of this study was to evaluate the different components of left atrial (LA) dysfunction predictors in asymptomatic primary systemic hypertension patients with preserved left ventricular (LV) ejection fraction, particularly using LA 4-dimensional (4D) longitudinal and circumferential strain values., Methods and Results: Patients with no left ventricular hypertrophy (NLVH) and left ventricular hypertrophy (LVH) are all asymptomatic regarding primary blood hypertension. Thirty NLVH patients and 30 LVH patients according to LV mass index and 40 controls analyzed by 4D echocardiography were prospectively enrolled. LA volumes and longitudinal and circumferential strains were measured using 4D volume-strain echocardiography with a Vivid E95 Version 203 instrument. Correlation analysis indicated a significant relation between LV 4D mass index and LA 4D longitudinal/circumferential strain (r = -0.446 to 0.381, p = 0.000-0.042). LVH patients had a reduced LA emptying fraction compared with NLVH patients and control subjects (p < 0.01). NLVH patients had an impaired LA conduit function and increased contractile function compared with the control group (p < 0.01). LVH patients had increased LA volumes and significantly decreased reservoir, conduit and contractile functions compared with the controls (p < 0.01). LVH patients had increased LA volumes and decreased reservoir and contractile functions compared with NLVH patients (p < 0.01). The clinical utility of LA 4D volume-strain measurement was verified by receiver-operating characteristic curve analysis showing larger net benefits as evaluated with NLVH, LVH and control group comparisons. Interclass correlation coefficients of interobserver and intraobserver assessments in the LV and LA 4D value evaluations were >0.75 and >0.85, respectively., Conclusions: LVH patients showed increased LA volumes and decreased LA emptying fractions. LA reservoir, conduit and contractile functions were significantly impaired in LVH patients. Decreased LA conduit function and increased contractile function were revealed in NLVH patients. LA volumetric and functional analyses with 4D volume-strain echocardiography may facilitate the recognition of subtle LA and LV dysfunctions in asymptomatic systemic hypertension patients., (© 2020 S. Karger AG, Basel.)

A Gram-negative chlorate-reducing bacterial strain XM-1 was isolated. The 16S rRNA gene sequence identified the isolate as Ochrobactrum anthropi XM-1, which was the first strain of genus Ochrobactrum reported having the ability to reduce chlorate. The optimum growth temperature and pH for strain XM-1 to reduce chlorate was found to be 30 °C and 5.0-7.5, respectively, under anaerobic condition. Strain XM-1 could tolerate high chlorate concentration (200 mM), and utilize a variety of carbohydrates (glucose, L-arabinose, D-fructose, sucrose), glycerin and sodium citrate as electron donors. In addition, oxygen and nitrate could be used as electron acceptors, but perchlorate could not be reduced. Enzyme activities related to chlorate reducing were characterized in cell extracts. Activities of chlorate reductase and chlorite dismutase could be detected in XM-1 cells grown under both aerobic and anaerobic conditions, implying the two enzymes were constitutively expressed. This work suggests a high potential of applying Ochrobactrum anthropi XM-1 for remediation of chlorate contamination., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To analyze the risk factors associated with mechanical ventilation before surgery in patients with acute traumatic cervical spinal cord injury(TCSCI)., Methods: According to whether preoperative mechanical ventilation, 59 patients with TCSCI admitted to our hospital from November 2016 to May 2018 were divided into mechanical ventilation(MV)group (37 cases) and non-mechanical ventilation(non-MV) group (22 cases). Falling from height was the most common causes of injury(30 cases, 50.8%), then was traffic accident(22 cases, 37.3%). The most common paraplegic plane was in C₁-C₄(36 cases, 61%). American Spinal Cord Injury Association(ASIA) injury degree and ASIA exercise score(AMS) were used to assess the extent of affected neurological plane and spinal cord injury. Trauma severity score(ISS) was used to evaluate the severity of the injury. Multivariate Logistic regression was used to analyze the risk factors for mechanical ventilation in TCSCI. ROC curves were used to assess the value of AMS and ISS in predicting mechanical ventilation., Results: Univariate analysis showed that the percentage of male, complete injury and related injuries in the MV group were significantly higher than those in the non-MV group( P <0.05). The AMS score of the MV group was significantly lower than that of the non-MV group (16.4±10.7 vs 39.1±9.5, P <0.001), and the ISS score was significantly higher than that of the non-MV group(31.6±8.0 vs 26.5±6.7, P= 0.015). Multivariate Logistic regression analysis showed that AMS[ OR= 3.340, 95% CI(1.321, 6.242), P <0.001] and ISS [ OR= 1.120, 95% CI(0.306, 3.786), P <0.001] were significant risk factors on predicting the need for mechanical ventilation.The ROC analysis showed that the area under the ROC curve(AUC) of AMS was significantly higher than that of ISS(0.899 vs 0.685, P <0.05)., Conclusions: AMS and ISS at admission can be used as predictors of early mechanically assisted ventilation., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Objectives: Avian influenza viruses (AIVs) poise significant risk to human health and the poultry industry. We evaluated the transmission risk along the poultry supply chain., Methods: During October 2015 and July 2016, four rounds of cross-sectional surveys were performed to characterize AIV spread in farms, transport vehicles, slaughterhouses, wholesale and retail live poultry markets (LPMs). Poultry cloacal and oral swabs, environmental swabs, bioaerosol samples and human sera were collected. Poultry and environmental samples were tested for AIVs by rRT-PCR, further subtyped by next generation sequencing. Previous human H9N2 infections were identified by hemagglutination inhibition and microneutralization tests. Logistic regression was fitted to compare AIV transmission risk in different settings., Results: AIVs was detected in 23.9% (424/1771) of the poultry and environmental samples. AIV detection rates in farms, transport vehicles, wholesale and retail LPMs were 4.5%, 11.1%, 30.3% and 51.2%, respectively. 5.2%, 8.3% and 12.8% of the poultry workers were seropositive in farms, wholesale and retail LPMs, respectively. The regression analysis showed that virus detection and transmission risk to human increased progressively along the poultry supply chain., Conclusions: Strengthening control measures at every level along the poultry supply chain, using a one health approach, is crucial to control AIV circulation., (Copyright © 2019. Published by Elsevier Ltd.)

Chronic lymphocytic leukemia（CLL）is a malignant hematologic disease with heterogeneous clinical course, about two thirds of patients exhibit a long survival, but the remaining third of patients show aggressiveness of disease or poor response to conventional treatment even drug resistance. Studies suggested that tumor microenvironment possesses a critical effect in CLL disease progression in recent years. Monocyte/macrophage, as an important componens of tumor microenvironment, play a promotive role in the growth and drug reistance of tumor cells by direct cell-to-cell contact, secreting cytokines and suppressing antitumor responses. Therefore, exploring the monocyte/macrophage in CLL can provide theoretic basis for target treatment of CLL. In this review, the function of monocyte/macrophage and recent advances in therapy of CLL are discussed.

Objective: To investigate the effect of sevoflurane on hepatic ischemia-reperfusion injury in rats via janus kinase 2/signal transducer and activator of transcription 3 (JAK2-STAT3) pathway., Materials and Methods: Forty healthy male Sprague-Dawley (SD) rats were randomly divided into sham group (n=10), model group (HIRI group, n=10), sevoflurane intervention group (SF group, n=10), and sevoflurane combined with AG490 intervention group (AG490 group, n=10). Liver and serum samples were collected after reperfusion for 6 h. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), interleukin (IL) -1β, IL-6 and tumor necrosis factor (TNF) -α were detected by enzyme-linked immunosorbent assay (ELISA). JAK2, STAT3, p-JAK2 and p-STAT3 were detected by Western-blot. The expression level of cobalt quenching technique was used to detect the permeability of mitochondrial membrane permeability transition pore (mPTP)., Results: The levels of ALT, AST, AKP, IL-1β, IL-6 and TNF-α in HIRI group were higher than those in sham group (p < 0.05), those in SF group were lower than those in HIRI group (p < 0.05), while those in AG490 group were higher than those in SF group (p < 0.05). The levels of JAK2 protein, pJAK2 protein, STAT3 protein and P STAT3 protein in HIRI group were lower than those in sham group (p < 0.05); the levels of each protein in SF group were higher than those in HIRI group (p < 0.05), while those in AG490 group were lower than those in SF group (p < 0.05). The open degree of HIRI group was higher than that of sham group (p < 0.05); SF group was lower than that of HIRI group, and AG490 group was higher than that of SF group (p < 0.05)., Conclusions: Sevoflurane can significantly improve HIRI and reduce hepatic immune inflammation in rats. The mechanism may be related to activating JAK2-STAT3 pathway and inhibiting the overopening of mPTP.

Background: Accumulating evidence indicates that regulatory T cells (Tregs) play an important role in the maintenance of immune tolerance. And dysfunction or deficiency of Tregs is thought to be involved in the pathogenesis of Multiple Sclerosis (MS). Nevertheless, previous studies reporting Tregs in patients were controversial due to the different markers adopted to identify Tregs. To clarify the status of Tregs in the pathogenesis of MS patients, we did a meta-analysis of the results published previously to assess the proportion of Tregs in peripheral blood (PB) in patients with MS., Methods: We systematically searched Embase, PubMed, Cochrane, Web of Knowledge, FDA.gov, and Clinical Trials.gov for the studies reporting the proportion of Tregs in MS patients. Our main endpoints were the proportion of Tregs among CD4 + T cells in PB defined by different markers. We assessed pooled data by using a random-effects model. Our meta-analysis had been registered at International Prospective Register of Systematic Reviews (PROSPERO) (number CRD42017064906)., Results: Of 885 identified studies, a total 16 studies were selected in our analysis. There was no significant difference between MS patients and control subjects in Tregs identified by all Tregs definition methods [-0.07, (-0.46, 0.31, p = 0.706)] and Tregs defined by "CD4 + CD25 + " [0.24, (-0.18, 0.65), p = 0.263]. Compared with control subjects, MS patients had a lower proportion of Tregs defined by "CD4 + CD25 + FOXP3 + " [-0.75, (-0.46,0.31), p = 0.001]., Conclusion: Under random effect model of meta-analysis, the data showed that the results of Tregs in MS were different according to the definition method; and the proportion of Tregs defined by "CD4 + CD25 + FOXP3 + " was decreased in MS. That result demonstrates that FOXP3 may be a vital definition of Tregs, and Tregs defined by stricter definition methods should be involved in the pathogenic mechanisms of MS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Increasing evidence indicates that cetuximab (CET) combined with chemoradiotherapy may be effective for patients with esophageal cancer. However, the recent results are still contradictory and no consensus has yet been reached on this issue. To evaluate the clinical effects and safety of CET, we conducted an updated meta-analysis by retrieving published data up to June 2018., Methods: A comprehensive literature search was performed in several electronic databases, including PubMed, Embase, the Cochrane Library, CNKI database and Chinese Biomedicine Database using subject terms and free terms. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to determine the efficiency and safety of CET., Results: This meta-analysis included 10 randomized controlled trials (RCTs). Five RCTs reported localized esophageal cancer and other five RCTs reported metastatic esophageal cancer. For these patients with localized esophageal cancer, CET could not significantly improve the response rate, overall survival and progression-free survival (PFS, 1-5 years). But CET treatment might increase the incidences of diarrhea (OR = 2.07; CI = 1.01-4.25) and rash (OR = 16.91; CI = 3.20-89.42). For other patients with metastatic esophageal cancer, the addition of CET significantly increased the response rate (OR = 3.34; CI = 1.90-5.88), disease control rate (OR = 2.92; CI = 1.49-5.71) and 2-year overall survival (OR = 2.78; CI = 1.20-6.46) compared with the control group. However, CET could not improve the 1-year overall survival and might make patients with metastatic esophageal cancer more susceptible to rash (OR = 5.50; CI = 2.14-14.14). No significant differences in other adverse effects were found between the two groups., Conclusions: Our findings suggested that adding CET to multimodal therapy significantly improved response rate and disease control rate for patients with metastatic esophageal cancer rather than patients with localized esophageal cancer. CET might be a safe therapeutic choice, but CET failed to significantly improve the overall survival and PFS for patients with localized or metastatic esophageal cancer.

An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43 (GAP-43) is closely associated with neurite outgrowth and axon regeneration during neural development. We speculate that an enriched environment can reduce damage to dopaminergic neurons by affecting the expression of GAP-43. This study is designed to test this hypothesis. Three-month-old female senescence-accelerated mouse prone 8 (SAMP8) mice were housed for 3 months in an enriched environment or a standard environment. These mice were then subcutaneously injected in the abdomen with 14 mg/kg MPTP four times at 2-hour intervals. Morris water maze testing demonstrated that learning and memory abilities were better in the enriched environment group than in the standard environment group. Reverse-transcription polymerase chain reaction, immunohistochemistry and western blot assays showed that mRNA and protein levels of GAP-43 in the substantia nigra were higher after MPTP application in the enriched environment group compared with the standard environment group. These findings indicate that an enriched environment can increase GAP-43 expression in SAMP8 mice. The upregulation of GAP-43 may be a mechanism by which an enriched environment protects against MPTP-induced neuronal damage., Competing Interests: None

Pulmonary atresia witha ventricular septal defect and major aortopulmonary collateral arteries is an extremely rare congenital disorder characterized by a high risk of maternal mortality. We present the case of a 24-year-old primigravid woman with uncorrected pulmonary atresia, ventricular septal defect and major aortopulmonary collateral arterieswho presented at 35+5 weeks' gestation. Based on the pathophysiology of the congenital cardiac lesion, cesarean delivery was performed under epidural anesthesia under management by a multidisciplinary team. This report highlights the anesthesia management of a rare uncorrected congenital cardiac lesion for cesarean delivery., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Zoletil is an anesthetic and immobilizing drug that has been used in the veterinary field for over 50 years; however, the effect of Zoletil, or its constituents, on brain cystathionine β-synthase (CBS) remains unknown. Here, we aimed to determine the effect of Zoletil on rat brain CBS by administering a single intraperitoneal injection of the drug and examining hydrogen sulfide (H 2 S) and CBS levels in the cerebral cortex, hippocampus, and thalamus following three distinct behavioral phenotypes associated with the sedation procedure (e.g., loss of the righting reflex, return of the righting reflex, and return of walking). Zoletil administration resulted in significant decreases of endogenous H 2 S in the cerebral cortex, hippocampus, and thalamus, and H 2 S was observed to increase in these brain regions when rats recovered from the anesthesia. Quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry revealed that CBS expression in the cerebral cortex and hippocampus exhibited the same trend as endogenous H 2 S following Zoletil administration. In summary, our results demonstrated that Zoletil induced the expression of CBS which could exert region-specific regulation of H 2 S in the cerebral cortex and hippocampus., (Copyright © 2017. Published by Elsevier B.V.)

Background: L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria neurometabolic disease that is inherited as an autosomal recessive mode and have a variety of symptoms, such as psychomotor developmental retardation, epilepsy, cerebral symptoms as well as increased concentrations of 2-hydroxyglutarate (2-HG) in the plasma, urine and cerebrospinal fluid. The causative gene of L-2-HGA is L-2-hydroxyglutarate dehydrogenase gene (L2HGDH), which consists of 10 exons., Case Presentation: We presented a rare patient primary diagnosis of L-2-HGA based on the clinical symptoms, magnetic resonance imaging (MRI), and gas chromatography-mass spectrometry (GC-MS) results. Mutational analysis of the L2HGDH gene was performed on the L-2-HGA patient and his parents, which revealed two novel mutations in exon 3: a homozygous missense mutation (c.407 A > G, p.K136R) in both the maternal and paternal allele, and a heterozygous frameshift mutation [c.407 A > G, c.408 del G], (p.K136SfsX3) in the paternal allele. The mutation site p.K136R of the protein was located in the pocket of the FAD/NAD(P)-binding domain and predicted to be pathogenic., Conclusion: We predicted the homozygous missense mutation (c.407 A > G, p.K136R) was considered as the pathogenic mutation of the patient. The study highlights the power of pedigree analysis in order to interpret novel mutations.