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T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) exhibits unique, cell type- and context-dependent characteristics and functions. Here, we report that TIM-3 on myeloid cells plays essential roles in modulating lung inflammation. We found that myeloid cell-specific TIM-3 knock-in (FSF-TIM3/LysM-Cre + ) mice have lower body weight and shorter lifespan than WT mice. Intriguingly, the lungs of FSF-TIM3/LysM-Cre + mice display excessive inflammation and features of disease-associated pathology. We further revealed that galectin-3 levels are notably elevated in TIM-3-overexpressing lung-derived myeloid cells. Furthermore, both TIM-3 blockade and GB1107, a galectin-3 inhibitor, ameliorated lung inflammation in FSF-TIM3/LysM-Cre +/- mice. Using an LPS-induced lung inflammation model with myeloid cell-specific TIM-3 knock-out mice, we demonstrated the association of TIM-3 with both lung inflammation and galectin-3. Collectively, our findings suggest that myeloid TIM-3 is an important regulator in the lungs and that modulation of TIM-3 and galectin-3 could offer therapeutic benefits for inflammation-associated lung diseases., (© 2024. The Author(s).)

In situ pulmonary arterial thrombosis (ISPAT) refers to the formation of new blood clots in the pulmonary arterial system in the absence of pre-existing clots in the peripheral venous system. With the emergence and prevalence of COVID-19, ISPAT has become an increasingly important cause of pulmonary arterial thrombosis (PAT) alongside thromboembolism. Several factors such as hypoxia, inflammation, endothelial dysfunction, and hypercoagulable state can lead to ISPAT, which is associated with a number of conditions such as thoracic trauma, partial lung resection, pulmonary infectious disease, pulmonary vasculitis, connective tissue diseases, severe pulmonary hypertension, radiation pneumonitis, and acute chest syndrome in sickle cell disease. It is important to differentiate between pulmonary thromboembolism (PTE) and ISPAT for proper disease management and prognosis. In this review, we summarized the characteristics of ISPAT under different disease conditions, the methods to distinguish ISPAT from PTE, and the best treatment strategies. We hoped that this review could improve clinicians' understanding of this independent disease and provide guidance for the refined treatment of patients with PAT.

Objective: Anorexia nervosa (AN) is a serious psychiatric illness associated with significant medical and psychiatric comorbidity and impairment. Theoretical models of AN and self-report studies suggest that negative self-evaluation (i.e., low self-esteem) is related to the development and maintenance of AN. The goal of this study was to extend findings from self-report methodology using a neurocognitive task that probes self-evaluation implicitly and explicitly., Method: We compared female adolescent and adult patients with AN (n = 35) and healthy controls (HC, n = 38) on explicit (i.e., endorsement of words as self-relevant), implicit (recall, recognition, reaction time), and composite (i.e., valence index, bias score, drift rates) indices of self-evaluation. We applied a drift-diffusion model to compute the drift rates, reflecting participants' decision-making process as to whether words were self-relevant. The association between self-evaluation indices and eating disorder severity was examined., Results: There were significant Group × Condition interaction effects for all explicit and implicit measures (all p's ≤ .01), where the AN group endorsed, recalled, and recognized more negative relative to positive words than HC. The AN group had more negative valence index and bias scores, and slower drift rate away from negative words, reflecting more negative self-evaluation. The finding for recall was attenuated when individuals with depression were excluded. Measures of self-evaluation bias were not related to eating disorder severity., Discussion: Using a neurocognitive approach that includes explicit and implicit indices of bias, results suggest that patients with AN have more negative self-evaluation. Due to the cross-sectional design, additional studies are needed to further evaluate directionality., Public Significance: Negative self-evaluation/low self-esteem is thought to contribute to eating disorder symptoms. Findings of this study using a neurocognitive task to probe self-evaluation suggested that individuals with anorexia nervosa have more negative self-evaluation, reflected by endorsing and remembering more negative (than positive) words compared to healthy controls, and doing so faster. Targeting the construct of negative self-evaluation in treatment of AN may be warranted., (© 2024 Wiley Periodicals LLC.)

As one of the three major urban agglomerations in China, the Beijing-Tianjin-Hebei Region has strong economic strength but its ecological fragility is very prominent. To pursue the comprehensive development of economy and ecology, it is very important to analyze the ecological environment in the Beijing-Tianjin-Hebei Region. Here, the Beijing-Tianjin-Hebei Region was selected as the research area, and 19 indicators were selected to construct an evolution system based on the PSRM model. The temporal and spatial evolution characteristics of ecological vulnerability in the Beijing-Tianjin-Hebei Region were explored by combining the order relation method, CRITIC method, Theil index, and hot spot analysis, and the influencing factors were calculated via geographic detector. The results showed that:① the ecological vulnerability first increased and then decreased in the Beijing-Tianjin-Hebei Region. The vulnerable areas showed a northeast-southwest trend, and the ecological environment in the northeast and southwest regions was better than that in the central and southern regions. The area of slight vulnerability in 2014 increased by 6803.01 km 2 compared with that in 2009. The area of mild vulnerability decreased by 130.41 km 2 , and the area of moderate vulnerability decreased by 26537.31 km 2 compared with that in 2009. The areas of severe and extremely vulnerable status increased by 19512.9 km 2 and 351.81 km 2 , respectively, compared with those in 2009. The habitat situation in the Beijing-Tianjin-Hebei Region improved significantly from 2014 to 2019. Compared with that in 2014, the areas of mild, moderate, severe, and extremely vulnerable decreased by 2248.29 km 2 , 2220.21 km 2 , 7988.67 km 2 , and 55.98 km 2 , respectively. The light area increased by 12513.15 km 2 compared with that in 2014. ② According to the calculation results of the Theil index, the spatial correlation degree of ecological vulnerability in the Beijing-Tianjin-Hebei Region exhibited a V-shaped fluctuation, and the spatial pattern of the cold and hot areas was predominantly consistent with that of the vulnerability. ③ Biological abundance, PM 10 , and the human disturbance index had a significant influence on the spatial differentiation of ecological vulnerability in the Beijing-Tianjin-Hebei Region. Based on the results of ecological vulnerability analysis, some suggestions on the ecological environment and sustainable development in the Beijing-Tianjin-Hebei Region were proposed.

Objective: To investigate the association between long-term fasting blood glucose (FPG) variability and all-cause mortality in patients with type 2 diabetes. Methods: A total of 7 174 type 2 diabetic patients included in National Basic Public Health Service Program in Changshu of Jiangsu Province were recruited as participants. Long-term glucose variability was assessed using standard deviation ( SD ), coefficient of variation ( CV ), average real variability ( ARV ), and variability independent of the mean ( VIM ) across FPG measurements at the more than three visits. Death information were mainly obtained from the death registry system in Jiangsu. Then Cox proportional hazards regression models were used to estimate the associations of four variability indicators and all-cause mortality's hazard ratios ( HR s) and their 95% CI s. Results: Among 55 058.50 person-years of the follow-up, the mean follow-up time was 7.67 years, and 898 deaths occurred during the follow-up period. After adjustment, compared with T 1 group, the Cox regression model showed that HR s of T 3 group in SD , CV , ARV and VIM were 1.24 (95% CI : 1.03-1.49), 1.20 (95% CI : 1.01-1.43), 1.28 (95% CI : 1.07-1.55) and 1.20 (95% CI :1.01-1.41), respectively. HR s of per 1 SD higher SD , CV , ARV and VIM were 1.13 (95% CI : 1.06-1.21), 1.08 (95% CI : 1.01-1.15), 1.05 (95% CI : 1.00-1.12) and 1.09 (95% CI : 1.02-1.16) for all-cause mortality, respectively. In the stratified analysis, age, gender, hypoglycemic agent and insulin uses had no effect on the above associations (all P for interaction >0.05). Conclusion: Long-term FPG glycemic variability was positively associated with the risk of all-cause mortality in type 2 diabetes patients.

Objective: To investigate the distribution of blood pressure and analyze the associated factors of blood pressure of the elderly with type 2 diabetes in Jiangsu Province. Methods: The elderly over 60 years old participants with type 2 diabetes in the communities of Huai'an City and Changshu City, Jiangsu Province were selected in this study. They were divided into two groups: taking antihypertensive drugs and not taking antihypertensive drugs. The demographic characteristics, such as age and sex, and relevant factors were collected by questionnaire. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by physical examination. The percentile of SBP and DBP in each age group of men and women were described. The kernel density estimation curve was used to show the blood pressure distribution. The trend of blood pressure with age was fitted by locally weighted regression. The logistic regression model was used to analyze relevant factors of blood pressure. Results: A total of 12 949 participants were included in this study, including 7 775 patients in the antihypertensive drug group and 5 174 patients in the group without antihypertensive drugs. The SBP of participants was concentrated at 140-160 mmHg, and their DBP was concentrated at 75-85 mmHg. There were significant differences in the distribution of blood pressure among the subgroups of body mass index (BMI) and rural areas whether taking antihypertensive drugs and not. For participants aged under 80 years old, the SBP showed an increasing trend with age and the DBP showed a decreasing trend with age. Age, BMI ≥24 kg/m 2 , fasting blood glucose ≥7.0 mmol/L, living in rural areas and no smoking were influencing factors of the elevated SBP; BMI ≥24 kg/m 2 , male, living in rural areas, no smoking, drinking alcohol and not receiving drug hypoglycemic treatment were influencing factors of the elevated DBP. Conclusion: The SBP of older diabetic adults in Jiangsu Province is at a high level, and the distribution of blood pressure is significantly different between men and women in taking antihypertensive drugs group. The SBP presents a rising trend and the DBP is decreasing at the age of 60-80 years. The blood pressure level of this population are mainly affected by age, BMI, urban and rural areas, smoking.

Background: Along with the rapid growth of the global aging society, the mobile and health digital market has expanded greatly. Countless mobile medical apps (mmApps) have sprung up in the internet market, aiming to help patients with chronic diseases achieve medication safety., Objective: Based on the medication safety action plans proposed by the World Health Organization, we aimed to explore the effectiveness of mmApps in ensuring the medication safety of patients with chronic diseases, including whether mmApps can improve the willingness to report adverse drug events (ADEs), improve patients' medication adherence, and reduce medication errors. We hoped to verify our hypothesis through a systematic review and meta-analysis., Methods: The meta-analysis was performed in strict accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and included literature searched from 7 databases-PubMed, Web Of Science, Embase, CINAHL, China National Knowledge Infrastructure, Wanfang, and SinoMed. The publication time was limited to the time of database establishment to April 30, 2022. Studies were screened based on inclusion and exclusion criteria. The data extracted included authors, years of publication, countries or regions, participants' characteristics, intervention groups, and control groups, among others. Our quality assessment followed the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions, Version 6.3. RevMan 5.2 software (Cochrane Collaboration) was used to analyze the statistical data, and a sensitivity analysis was performed to assess data stability. The degree of stability was calculated by using a different statistical method and excluding large-sample studies from the analysis., Results: We included 8 studies from 5 countries (China, the United States, France, Canada, and Spain) that were published from January 1, 2014, to December 31, 2021. The total number of participants was 1355, and we analyzed the characteristics of included studies, each app's features, the risk of bias, and quality. The results showed that mmApps could increase ADE reporting willingness (relative risk [RR] 2.59, 95% CI 1.26-5.30; P=.009) and significantly improve medication adherence (RR 1.17, 95% CI 1.04-1.31; P=.007), but they had little effect on reducing medication errors (RR 1.54, 95% CI 0.33-7.29; P=.58)., Conclusions: We analyzed the following three merits of mmApps, with regard to facilitating the willingness to report ADEs: mmApps facilitate more communication between patients and physicians, patients attach more importance to ADE reporting, and the processing of results is transparent. The use of mmApps improved medication adherence among patients with chronic diseases by conveying medical solutions, providing educational support, tracking medications, and allowing for remote consultations. Finally, we found 3 potential reasons for why our medication error results differed from those of other studies., Trial Registration: PROSPERO International Prospective Register of Systematic Reviews CRD42022322072; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=322072., (©Ting ting Zhou, Rui Wang, Si jia Gu, Li ling Xie, Qing hua Zhao, Ming zhao Xiao, Yu lu Chen. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 22.11.2022.)

Testicular endothelial cells have been found to play an important role in spermatogenesis and fertility, but their mechanism is obscure. Exosomes released by various cells are recognized as cell-cell communication mediators during the initiation and progression of many diseases. Therefore, the current study aimed to investigate the protein and miRNA components of human testicular endothelial cell-derived exosomes (HTEC-Exos) and to explore their potential effects on spermatogenesis. In this study, HTEC-Exos were first isolated by the ultracentrifugation method, and then identified by nanoparticle tracking analysis, transmission electron microscopy (TEM), and western blotting. The characteristics of HTEC-Exos were examined by liquid chromatography-mass spectrometry and microRNA (miRNA) chip analysis. Bioinformatics analysis was performed to explore the potential role of the exosomal content on spermatogenesis. A total of 945 proteins were identified, 11 of which were closely related to spermatogenesis. A total of 2578 miRNAs were identified. Among them, 30 miRNAs demonstrated potential associations with male reproductive disorders, such as azoospermia, and spermatogenesis disorders. In particular, 11 out of these 30 miRNAs have been proven to be involved in spermatogenesis based on available evidence. This study provides a global view of the proteins and miRNAs from HTEC-Exos, suggesting that HTEC-Exos may function as potential effectors during the process of spermatogenesis., Competing Interests: None

Background: The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility., Objective: The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD., Methods: A prospective, diagnostic case-control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug-naïve patients with PD, and 185 non-PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification., Results: In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%-96%), 95% (95% CI: 93%-97%), and 19.16 (95% CI: 13.52-27.16) and 0.10 (95% CI: 0.05-0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug-naïve were 89% (95% CI: 75%-96%), 86% (95% CI: 81%-91%), and 6.6 (95% CI: 4.51-9.66) and 0.13 (95% CI: 0.05-0.32), respectively., Conclusions: Tests using sniffer dogs may be a useful, noninvasive, fast, and cost-effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society., (© 2022 International Parkinson and Movement Disorder Society.)

With the application of high-resolution chest imaging system and lung cancer screening program, patients with multiple primary lung cancer (MPLC) are becoming a growing population in clinical practice. However, the diagnostic criteria of MPLC and its differentiation from intrapulmonary metastasis of lung cancer (IM) are still controversial, especially in cases with similar histology. On the basis of reviewing the existing literature, this paper discusses the changes of the diagnostic criteria of MPLC and the differential diagnosis methods of imaging, histology and molecular genetics of MPLC and IM, and briefly introduces the application of multidisciplinary diagnosis, algorithm, predictive model and artificial intelligence in the differential diagnosis of MPLC. In addition, we also discuss the latest progress in the treatment of MPLC. Radical surgery is the main method for the treatment of MPLC. Stereotactic body radiation therapy (SBRT) is safe and feasible for inoperable MPLC patients, and targeted therapy and immunotherapy can also be used in MPLC after appropriate patient selection.

Objective: To investigate the current status and further development of Panax genus and 6 important individual species including P. notoginseng, P. quinquefolium, P. vietnamensis, P. japonicus, P. stipuleanatus and P. zingiberensis., Methods: The bibliometric analysis was based on the Web of Science core database platform from Thomson Reuters. Totally, 7,574 records of scientific research of Panax species published from 1900-2019 were analyzed. The statistical and visualization analysis was performed by CiteSpace and HistCite software., Results: The academic research of Panax species increase promptly. Plant science is the main research field while research and experimental medicine and agricultural engineering will be the further development tendency. Particularly, the discrimination research of P. notoginseng will be the research tendency among Panax species, especially diversity research. In addition, P. vietnamensis deserves more attention in the genus Panax., Conclusion: This research provides a reference for further research of the genus and individual species., (© 2021. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Extracellular vesicles (EVs) contain thousands of proteins and nucleic acids, playing an important role in cell-cell communications. Sertoli cells have been essential in the testis as a "nurse cell". However, EVs derived from human Sertoli cells (HSerCs) have not been well investigated., Methods: EVs were isolated from HSerCs via ultracentrifugation and characterized by transmission electron microscopy, tunable resistive pulse sensing, and Western blotting. The cargo carried by HSerCs-EVs was measured via liquid chromatography-mass spectrometry and GeneChip miRNA Arrays. Bioinformatic analysis was performed to reveal potential functions of HSerCs-EVs., Results: A total of 860 proteins with no less than 2 unique peptides and 88 microRNAs with high signal values were identified in HSerCs-EVs. Biological processes related to molecular binding, enzyme activity, and regulation of cell cycle were significantly enriched. Specifically, many proteins in HSerCs-EVs were associated with spermatogenesis and regulation of immune system, including Septins, Large proline-rich protein BAG6, Clusterin, and Galectin-1. Moreover, abundant microRNAs within HSerCs-EVs (miR-638, miR-149-3p, miR-1246, etc.) had a possible impact on male reproductive disorders such as asthenozoospermia and oligozoospermia., Conclusions: Our study has shown that HSerCs-EVs contain diverse components such as proteins and microRNAs. Further research is required to evaluate HSerCs-EVs in spermatogenesis, which are underutilized but highly potent resources with particular promise for male infertility., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Icariside II (ICA II), an active flavonoid monomer, has been proven to restore post-prostatectomy erectile dysfunction in rats; however, the high cost of extraction from natural plants limits the application of ICA II., Objective: To investigate the therapeutic effect and possible mechanism of action of YS-10, a new flavonoid compound, which was designed and synthesized based on the structure of ICA II in a rat model in of cavernous nerve injury., Materials/methods: Eight of 32 adult male Sprague-Dawley rats were selected as the normal control (NC) group and received vehicle treatment. The remaining rats were subjected to bilateral cavernous nerve injury (BCNI) and randomized into three groups: BCNI group, BCNI + ICA II group (2.5 mg/kg/day), and BCNI + YS-10 group (2.5 mg/kg/day). The total procedure lasted for 21 days, followed by a washout period of 3 days. All animals were evaluated for erectile function, and tissues were harvested for histopathological analyses., Results: It was observed that in YS-10 group, the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP) and the area under the ICP/MAP curve were effectively enhanced. The maximum ICP/MAP increased by 30% in the YS-10 group (0.86 ± 0.085) compared with the BCNI group (0.66 ± 0.058), which is close to 82% of the NC group (1.05 ± 0.033). Histopathological changes demonstrated significant reduction of smooth muscle atrophy, collagen deposition, and endothelial and neural dysfunction after YS-10 treatment, which have no statistical differences compared with ICA II group. Additionally, high-protein expression levels of β-Catenin and cyclin D1 were observed in the treatment groups., Conclusion: YS-10, a novel synthesized flavonoid compound, could effectively improve erectile dysfunction in rats after BCNI by alleviating pathological impairments; this effect may associate with the upregulation of β-Catenin and cyclin D1 in Wnt signaling pathway., (© 2021 American Society of Andrology and European Academy of Andrology.)

Bovine milk-derived extracellular vesicles (BM-EVs) are recognized as promising nanoscale delivery vectors owing to their large availability. However, few isolation methods can achieve high purity and yield simultaneously. Therefore, we developed a novel and cost-effective procedure to separate BM-EVs via "salting-out." First, BM-EVs were isolated from skimmed milk using ammonium sulfate. The majority of BM-EVs were precipitated between 30 and 40% saturation and 34% had a relatively augmented purity. The separated BM-EVs showed a spherical shape with a diameter of 60-150 nm and expressed the marker proteins CD63, TSG101, and Hsp70. The purity and yield were comparable to the BM-EVs isolated via ultracentrifugation while ExoQuick failed to separate a relatively pure fraction of BM-EVs. The uptake of BM-EVs into endothelial cells was dose- and time-dependent without significant cytotoxicity. The levels of endothelial nitric oxide syntheses were regulated by BM-EVs loaded with icariside II and miRNA-155-5p, suggesting their functions as delivery vehicles. These findings have demonstrated that it is an efficient procedure to isolate BM-EVs via "salting-out," holding great promise toward therapeutic applications., Competing Interests: R-LG has patent pending to China National Intellectual Property Administration. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tan, Fang, Xu, Nan, Song, Gu, Gu, Yuan, Xin, Zhou, Guan and Li.)

Background: Association between tea consumption and incident hypertension remains uncertain. This study conducted to examine the health effects of tea consumption on blood pressure progression and hypertension incidence., Methods: A population-based cohort of 38,913 Chinese participants without hypertension at baseline were included in the current study. Information on tea consumption was collected through standardized questionnaires. Associations of tea consumption with blood pressure progression and incident hypertension were analyzed using logistic regression models and Cox proportional hazards regression models, respectively., Results: During a median follow-up of 5.9 years, 17,657 individuals had experienced progression to a higher blood pressure stage and 5,935 individuals had developed hypertension. In multivariate analyses, habitual tea drinkers (≥ 3 times/week for at least six months) had a 17% lower risk for blood pressure progression [odds ratio (OR) = 0.83, 95% CI: 0.79-0.88] and a 14% decreased risk for incident hypertension [hazard ratio (HR) = 0.86, 95% CI: 0.80-0.91] compared with non-habitual tea drinkers. Individuals in different baseline blood pressure groups could obtain similar benefit from habitual tea drinking. In terms of tea consumption amount, an inverse, linear dose-response relation between monthly consumption of tea leaves and risk of blood pressure progression was observed, while the risk of incident hypertension did not reduce further after consuming around 100 g of tea leaves per month., Conclusions: Our study demonstrated that habitual tea consumption could provide preventive effect against blood pressure progression and hypertension incidence., (Copyright and License information: Journal of Geriatric Cardiology 2021.)

Background: Many factors affect the outcomes of anterior cruciate ligament (ACL) reconstruction surgery. However, few studies have examined the effects of local bone conditions on the reconstruction of the ACL. This study investigated the changes in the local bone mineral density (BMD) of the knee after rupture of the ACL with the view of using this information to guide treatment options., Methods: Patients with ACL rupture treated in our department from January 2017 to April 2019 were enrolled in this study. Prior to surgery, local BMD measurements were obtained from all patients and used to determine the appropriate method of ligament fixation. If the local BMD of the affected knee was not significantly lower than that of the healthy side, extrusion fixation was conducted. If the BMD was significantly lower than that of the healthy knee, suspension fixation was applied. The conditions of tunnel cutting or screw splitting, and tunnel enlargement or screw pull-out were observed during the surgery. The post-surgical function of the knee joint was evaluated regularly by physical examination, imaging data, the IKDC scale score, and the Lysholm score., Results: A total of 80 patients with unilateral ACL rupture were included. There were 64 males and 16 females. Decreased BMD was observed in the affected knee compared to the healthy knee for 68 patients. Patients with an ACL history of more than 3 months had lower BMD compared to patients with a history of less than 3 months. Tunnel enlargement and screw pull-out occurred in 2 patients, screw splitting occurred in 1 patient. The fixation mode was adjusted in real-time during the surgery for 3 patients. All patients were followed up for at least 12 months (mean 20.65±5.12 months). The IKDC score increased from 43.07±2.66 pre-surgery to 89.17±3.28 at the final follow-up, and similarly, the Lysholm score increased from 43.49±2.38 pre-surgery to 89.67±2.97 post-surgery., Conclusions: The measurement of local BMD before surgery may play a significant role in guiding the type of graft fixation. It is recommended that patients undergo surgical reconstruction within 3 months after injury.

Purpose: To evaluate whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS) can identify liver donation after brain death (DBD) and cardiac death (DCD) with the risk of developing short-term primary graft dysfunction (PGD) or arterial and biliary complications within 1 year., Materials and Methods: Consecutive DBD and DCD donors who underwent DUS/CEUS examinations before surgical procurement from February 2016 to June 2018 at our institution were included. The US and CEUS images of each donor liver were analysed, and the parameters were recorded., Results: The mean time for US examination was 32 min (range, 20-59 min), and all donors tolerated the examination well. In terms of short-term outcomes, among the 52 eligible donor livers, 20 (38.5 %) of their recipients developed PGD. The multivariable analysis showed that decreased enhancement of donor livers on CEUS (OR = 15.976, 95 % CI: 1.652-154.628, P = 0.017) and high recipient model for end-stage liver disease (MELD) scores (OR = 1.050, 95 % CI: 1.004-1.099, P = 0.034) before liver transplantation (LT) were independent factors of PGD. In contrast, for long-term complications, among the 48 eligible donor livers, 16 (33.3 %) developed arterial or biliary complications within 1 year. The multivariable analysis did not show any independent factors of arterial or biliary complications within 1 year., Conclusions: A decrease in enhancement on CEUS is an independent risk factor for poor short-term outcomes of LT. CEUS may be promising for predicting post-LT outcomes of critically ill donors effectively and safely by evaluating the haemodynamic changes in DBD and DCD donor livers., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Broad hemodynamic changes, is believed to have a profoundly damaging effect on donor livers after brain death (DBD) or cardiac death (DCD). It remains unclear whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS), the imaging modalities to evaluate perfusion, could provide more information of liver discarded., Objective: To evaluate the ability of DUS and CEUS to predict the risk of DBD or DCD liver discarded., Methods: The consecutive DBD or DCD donors with DUS/CEUS examinations before surgical procurement from February 2016 to June 2018 at our institution were included. The US and CEUS images of each donor liver were analyzed and the parameters were recorded., Results: Among the 67 eligible donor livers, 15 (22.4%) were discarded and 52 (77.6%) were used. The discarded livers showed prolonged SAT of hepatic artery (0.08s vs 0.06s, OR = 2.169, P = 0.008) on DUS, less cases with homogeneous enhancement (40.0% vs 73.1%, OR = 0.243, P = 0.028) on CEUS, more cases with decreased enhancement (53.3% vs 19.2%, OR = 4.800, P = 0.009), and less difference of the peak time between portal vein and liver parenchymal (0.5s vs 6.7s, OR = 0.917, P = 0.034). The multivariable analysis showed that donor liver with prolonged SAT of hepatic artery (OR = 7.304, 95% CI: 1.195-44.655, P = 0.031) and decreased enhancement (OR = 2.588, 95% CI: 1.234-5.426, P = 0.012) were independent factors of liver discarded., Conclusions: DUS/CEUS could be applied as a promising predictive tool to screen high-risk liver donors. The prolonged SAT of hepatic artery on DUS and the decrease of liver donor in enhancement on CEUS, indicating hemodynamic changes in DBD and DCD donor livers, were risk factors of liver discarded.

This study aimed to compare the effects of bilateral cavernous nerve crushing (BCNC) and bilateral cavernous nerve resection (BCNR) on intracavernous pressure (ICP) and cavernous pathology in rats and to explore the optimal treatment time for the BCNC and BCNR models. Seventy-two male rats aged 12 weeks were randomly divided into three equal groups: Sham (both cavernous nerves exposed only), BCNC (BCN crushed for 2 min), and BCNR (5 mm of BCN resected). Erectile function was then measured at 1 week, 3 weeks, and 5 weeks after nerve injury, and penile tissues were harvested for histological and molecular analyses by immunohistochemistry, immunofluorescence, Western blot, and cytokine array. We found that erectile function parameters including the maximum, area, and slope of ICP/mean arterial pressure (MAP) significantly decreased after BCNR and BCNC at 1 week and 3 weeks. At 5 weeks, no significant differences were observed in ICP/MAP between the BCNC and Sham groups, whereas the ICP/MAP of the BCNR group remained significantly lower than that of the Sham group. After BCNC and BCNR, the amount of neuronal-nitric oxide synthase-positive fibers, smooth muscle cells, and endothelial cells decreased, whereas the amount of collagen III content increased. These pathological changes recovered over time, especially in the BCNC group. Our findings demonstrate that BCNC leads to acute and reversible erectile dysfunction, thus treatment time should be restricted to the first 3 weeks post-BCNC. In contrast, the self-healing ability of the BCNR model is poor, making it more suitable for long-term treatment research., Competing Interests: None

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease linked to oxidative stress, which is associated with significant morbidity. The NADPH oxidase complex (NOX) produces reactive oxygen species (ROS) that are among the key markers for determining RA's pathophysiology. Therefore, understanding ROS-regulated molecular pathways and their interaction is necessary for developing novel therapeutic approaches for RA. Here, by combining mouse genetics and biochemistry with clinical tissue analysis, we reveal that in vivo Rubicon interacts with the p22phox subunit of NOX, which is necessary for increased ROS-mediated RA pathogenesis. Furthermore, we developed a series of new aryl propanamide derivatives consisting of tetrahydroindazole and thiadiazole as p22phox inhibitors and selected 2-(tetrahydroindazolyl)phenoxy-N-(thiadiazolyl)propanamide 2 (TIPTP, M.W. 437.44), which showed considerably improved potency, reaching an IC 50 value up to 100-fold lower than an inhibitor that we previously synthesized reported N8 peptide-mimetic small molecule (blocking p22phox-Rubicon interaction). Notably, TIPTP treatment showed significant therapeutic effects a mouse model for RA. Furthermore, TIPTP had anti-inflammatory effects ex vivo in monocytes from healthy individuals and synovial fluid cells from RA patients. These findings may have clinical applications for the development of TIPTP as a small molecule inhibitor of the p22phox-Rubicon axis for the treatment of ROS-driven diseases such as RA.

To investigate the features of paramyxovirus respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (HMPV) infection and determine the effect of meteorological conditions in Guangzhou, a subtropical region of southern China. We collected 11,398 respiratory samples from hospitalized pediatric patients with acute respiratory illness between July 2009 and June 2016 in Guangzhou. The samples were tested simultaneously for 18 respiratory pathogens using real-time PCR. Local meteorological data were also collected for correlation analysis. Of 11,398 patients tested, 5606 (49.2%) patients tested positive for one or more pathogens; RSV, PIV, and HMPV were the first, sixth, and ninth most frequently detected pathogens, in 1690 (14.8%), 502 (4.4%), and 321 (2.8%) patients, respectively. A total 17.9% (4605/5606) of patients with positive results had coinfection with other pathogens. Significant differences were found in the prevalence of RSV, PIV, and HMPV among all age groups (p < 0.001). RSV and HMPV had similar seasonal patterns, with two prevalence peaks every year. PIV appeared alternatively with RSV and HMPV. Multiple linear regression models were established for RSV, PIV, and HMPV prevalence and meteorological factors (p < 0.05). RSV and PIV incidence was negatively correlated with monthly mean relative humidity; RSV and HMPV incidence was negatively correlated with sunshine duration; PIV incidence was positively correlated with mean temperature. We described the features of paramyxovirus infection in a subtropical region of China and highlighted the correlation with meteorological factors. These findings will assist public health authorities and clinicians in improving strategies for controlling paramyxovirus infection.

Objective: To evaluate the clinical efficacy of operation methods with or without a turned-over patella for treatment of C3-type patellar fractures., Methods: A total of 68 patients with C3-type patellar fractures undergoing open reduction and internal fixation were retrospectively selected and treated with a turned-over patella surgery (turned-over patella group, n = 30) or conventional therapy without turning over the patella (conventional group, n = 38). The intraoperative and postoperative indicators of the two groups were assessed and comparatively analyzed., Results: The bedridden time was significantly shorter in the turned-over patella group than in the conventional group (P = 0.002), while the range of motion (ROM) of knee joint was significantly higher in the turned-over patella group (P = 0.044). The Lysholm score was slightly higher in the turned-over patella group than in the conventional group, but the difference was not statistically significant (P = 0.055). No significant difference was observed between the two groups in terms of the operation time (P = 0.096), intraoperative blood loss (P = 0.543), time of weight bearing (P = 0.312), fracture healing time (P = 0.272), or complications (P = 1)., Conclusion: The turned-over patella operation method exhibited some superiority to conventional reduction-fixation approach for treatment of C3-type patellar fractures in terms of efficacy and safety by enlarging the ROM of the knee joint and promoting functional recovery., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Stachartone A (1), a novel phenylspirodrimane dimer, was isolated from cultures of the tin mine tailings-associated fungus Stachybotrys chartarum. Its structure was elucidated by means of spectroscopic methods. At the same time, compound (1) was tested for its cytotoxicity against five human cancer cell lines.

A new phenylspirodrimane dimer, named stachartarin A (1), was isolated from cultures of the tin mine tailings-associated fungus Stachybotrys chartarum. Its structures were elucidated by means of spectroscopic methods. At the same time, the compound was tested for its cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To investigate the association between ten single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors and pulse pressure (PP) as well as the relationships between gene-gene interaction between PPARα/δ/γ genes and PP. Methods: A total of 820 subjects, with 550 females and 270 males, were recruited from a cohort study of "Prevention of Metabolic Syndrome and Multi-metabolic Disorders in Jiangsu Province of China Study (PMMJS)" . Ten SNPs of PPARα/δ/γ genes were selected. GMDR software (version 1.0.1) was used to evaluate the gene-gene interactions among PPARs SNPs associated with PP. Results: The mean levels of PP in people with mutant genotype of rs1805192 in PPARγ genes (PA+AA) showed a significant increase by 1.341 mmHg (95 %CI : 0.431-2.252 mmHg) when compared to the persons with wild genotype (PP). In the subgroup of subjects with more than 30 mmHg levels of PP, a six-locus model comprised rs135539 of PPARα, rs2016520 of PPARδ, rs10865710, rs1805192, rs709158 and rs3856806 of PPARγ showed a highest level of prediction accuracy (0.577) and displayed a better cross-validation consistency (10/10). In the subgroup of subjects with less than 40 mmHg levels of PP, a two-locus model was statistically associated with PP with 0.628 of prediction accuracy and 10/10 of cross-validation consistency. Conclusion: PPARγ rs1805192 was associated with the occurrence of PP. Gene-gene interactions among rs135539 of PPARα, rs2016520 of PPARδ, rs10865710, rs1805192, rs709158 and rs3856806 of PPARγ were all significantly related to PP.

Zinc finger protein 687 (ZNF687), identified as a C2H2 zinc finger protein, has been found to be mutated and upregulated in giant cell tumor of bone and acute myeloid leukemia, suggesting an oncogenic role for ZNF687 in cancer. However, the clinical significance and precise role of ZNF687 in cancer progression are largely unknown. Herein, we report that ZNF687 was markedly upregulated in hepatocellular carcinoma (HCC) cell lines and HCC tissues, and was significantly correlated with relapse-free survival in HCC. ZNF687 overexpression greatly enhanced HCC cell capability for tumorsphere formation, invasion and chemoresistance in vitro, whereas inhibiting ZNF687 reduced these capabilities and inhibited HCC cell tumorigenic capability in vivo. Importantly, extreme limiting dilution analysis revealed that even 1 × 10 2 ZNF687-transduced cells could form tumors in vivo, indicating that ZNF687 contributes to HCC recurrence. Moreover, we demonstrate that ZNF687 transcriptionally upregulated the expression of the pluripotency-associated factors BMI1, OCT4 and NANOG by directly targeting their promoters. Therefore, our results suggest that ZNF687 has a promoter role in regulating HCC progression, which provides a potential therapeutic target for HCC in humans.

Biofilm coming from a reactor in which One-stage Autotrophic Nitrogen Removal Process exists was selected as inoculum in an expanded granular sludge bed reactor. A potential fast start-up procedure was tested in this research. Wastewater with low ammonium concentration between 60-100 mg·L -1 was applied. The results showed that a One-stage Autotrophic Nitrogen Removal Process was successfully established in 83 days under the following conditions: temperature at (30±2)℃ , pH at 7.8-8.2, dissolved oxygen (DO) at 0.2-1.1mg·L -1 and upflow velocity at 2.0-4.0m·h -1 . After the 83-day operation, the removal efficiencies of NH 4 + -N and TN were 99.4% and 80.7%, respectively. By controlling the reflux ratio and increasing the NH 4 + -N load, the reactor could maintain a stable state of low DO concentration. Nitrification and anaerobic ammonium oxidation became main reactions that maintained efficient and stable nitrogen removal performance. In addition, nitrite-oxidizing bacteria (NOB) were inhibited. In the start-up process, the average particle diameter of granular sludge increased from 174 to 296 μm. Moreover, scanning electron microscopy showed that the surface of granular sludge was smooth, and most microorganisms were bevibacteria and cocci. Finally, a fluorescence in situ hybridization experiment showed that ammonium oxidation bacteria and anaerobic ammonium oxidation bacteria were distributed on the surface and in the inner space of granular sludge, respectively. The research indicated that a stable autotrophic nitrogen removal granular sludge system was quickly established in the sludge bed.

Background: Caspase-cleaved Cytokeratin-18 (CCCK-18) is released during apoptosis. Serum CCCK-18 concentrations are associated with prognosis of some critical illness. We investigated the potential relationships between serum CCCK-18 concentrations and disease severity and long-term clinical outcomes after intracerebral hemorrhage., Methods: Serum CCCK-18 concentrations were determined in a total of 102 patients and 102 controls. Multivariate models were used to predict high concentration of CCCK-18 and 6-month clinical outcomes. The predictive values were evaluated based on areas under receiver operating curve., Results: Compared with controls, serum CCCK-18 concentrations were increased in patients (245.8±108.3U/l vs. 23.6±18.1U/l, P<0.001). National Institute of Health Stroke Scale scores [odds ratio (OR), 1.164; 95% confidence interval (CI), 1.027-1.320; P=0.003] and hematoma volumes (OR, 1.079; 95% CI, 1.018-1.205; P=0.008) were independent predictors of high concentration of CCCK-18. CCCK-18 was identified as an independent predictor of 6-month mortality (OR, 1.019; 95% CI, 1.010-1.038; P=0.013) and 6-month unfavorable outcome (OR, 1.017; 95% CI, 1.008-1.029; P=0.032) and possessed high predictive values., Conclusion: Increased serum CCCK-18 concentrations are associated with disease severity and clinical outcomes, suggesting that CCCK represent a novel prognostic predictive biomarker after intracerebral hemorrhage., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Understanding novel pairings in attractive degenerate Fermi gases is crucial for exploring rich superfluid physics. In this report, we reveal unconventional pairings induced by spin-orbit coupling (SOC) in a one-dimensional optical lattice, using a state-of-the-art density-matrix renormalization group method. When both bands are partially occupied, we find a strong competition between the interband Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) and intraband Bardeen-Cooper-Schrieffer (BCS) pairings. In particular, for the weak and moderate SOC strengths, these two pairings can coexist, giving rise to a new phase called the FFLO-BCS phase, which exhibits a unique three-peak structure in pairing momentum distribution. For the strong SOC strength, the intraband BCS pairing always dominates in the whole parameter regime, including the half filling. We figure out the whole phase diagrams as functions of filling factor, SOC strength, and Zeeman field. Our results are qualitatively different from recent mean-field predictions. Finally, we address that our predictions could be observed in a weaker trapped potential.

Objective: To analyze the related factors of the infection after operation of open tibiofibula fractures., Methods: The clinical data of 141 patients with open tibiofibula fractures underwent surgical treatment from June 2009 to December 2012 were retrospectively analyzed. All the patients were male and aged from 18 to 61 years old with an average of 39.2 years; all the fractures were unilateral. According to Gustilo typing of fracure, 5 cases were type I, 44 cases were type II, 27 cases were type III a, 56 cases were type III b and 9 cases were type III c. These clinical data included patients' age, gender, body mass index (BMI), underlying diseases, time of operation, fracture site, fracture type, fixation method, postoperative drainage, debridement condition and so on. The postoperative infection conditions were recorded, and the correlation between above factors and infections were analyzed. Finally, the significant related variables were introduced into a Logistic regression model to evaluated their risk., Results: Among the 141 patients, 22 cases developed with infection (15.6%). The significant relative factors with infection contained fixation method, debridement condition, underlying diseases and postoperative drainage (P < 0.05). The correlativities were stepped up in order, their odds ratios value was 2.451, 3.164, 3.414, 5.117, respectively., Conclusion: Active treatment for underlying diseases before operation, thorough debridement for open wound, suitable fixation method for fracture and thorough draining are effective measures in preventing postoperative infection.

The peroxisome proliferator-activated receptors (PPARs)-α, -β/δ, and -γ are the ligand-activated transcription factors that function as the master regulators of glucose, fatty acid and lipoprotein metabolism, inflammation, and atherosclerosis. Our aim was to test the association between ten single nucleotide polymorphisms of PPARs and CRP level, as well as their interaction with overweight/obesity. A sample population of 643 subjects was recruited from the prevention of MetS and multi-metabolic disorders in Jiangsu Province of China Study. The selected SNPs in PPAR α (rs135539, rs4253778, rs1800206), PPAR β/δ (rs2016520 and rs9794), and PPAR γ (rs10865710, rs1805192, rs709158, rs3856806, and rs4684847) were genotyped. After adjustment for smoking, alcohol consumption, SBP, DBP, TG, and HDL-C, rs1800206, rs709158, rs1805192, and rs4684847 polymorphisms were significantly associated with CRP level in normal weight subjects (P < 0.05). In the overweight/obese subjects, rs1800206 was also significant associated with CRP level (P<0.01). In addition, the rs709158, rs1805192, and rs4684847 polymorphisms were shown interactions with overweight/obesity to influence CRP level (P<0.05). PPARs polymorphisms are independently associated with CRP levels in Chinese Han population. Further, PPARs polymorphisms interact with overweight/obesity to set CRP levels.

Objective: To study clinical outcomes of serial tightening of reserved suture threads in delayed incision closure., Methods: From January 2005 to June 2013, 67 patients with delayed incision closure were treated with serial tightening of reserved suture threads. There were 37 males and 30 females, with an average age of 40 years old (ranged from 12 to 75 years old). Among them, 36 patients suffering from leg or forearm double fractures had the incision difficult to those primarily due to high tension or mergency; 13 patients had open wound which lasted for more than routine time for debridement and closure; 9 patients had wound infection; 9 patients had decompression incisions owing to compartment syndrome. The No. 4 suture thread was used to sew up the incision, and the 4 to 6 cm long thread was reserved at two ends of each thread. The reserved thread was tightened gradually from 2 to 4 days after operation according to conditions of swelling relieving. Finally, the reserved thread was not tied until the incision was completely closed., Results: After operation, the reserved threads were tightened and tied for 1 time in 6 patients, 2 times in 23 patients, 3 times in 27 patients, 4 times in 11 patients. Postoperative closure time ranged from 3 to 9 days, with an average of 6.2 days. All the incisions got delayed primary healing., Conclusion: The method of serial tightening of reserved suture threads to close delayed incision closure avoids a second operation, which is simple and obtains a fine result.

Peroxisome proliferator‑activated receptor γ (PPARγ) may play an important role in lipid metabolism directly or by inducing the transcription of target genes. The aim of the present study was to investigate the association between common variants at the PPARγ locus (C1431T and Pro12Ala polymorphisms) and lipid serum levels. The studied population consisted of 820 subjects randomly selected from the Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu Province cohort population. All subjects were interviewed and blood samples were obtained for laboratory analysis and DNA extraction. The TaqMan single nucleotide polymorphism genotyping assay was used for polymorphism genotyping. Individual polymorphisms and haplotype data were available for analysis. The 12Ala allele was found to be associated with significantly increased levels of triglyceride (TG) (P<0.01), whilst the 1431T allele was found to be associated with significantly increased levels of TG, total cholesterol (TC) and non‑high‑density lipoprotein (non‑HDL) (P<0.01). When P‑C, the most common haplotype, was used as the reference group, the P‑T, A‑C and A‑T haplotypes were found to be associated with significantly increased levels of TG (P<0.01). In addition, the A‑T haplotype was shown to be associated with significantly increased levels of TC and non‑HDL (P<0.01). In conclusion these results suggest that PPARγ gene variability may increase the risk of dyslipidemia.

This article describes the synthesis and biological evaluation of a chemical library of mibefradil analogues to investigate the effect of structural modification on in vitro stability. The construction of the dihydrobenzopyran structure in mibefradil derivatives 2 was achieved through two efficient approaches based on a diastereoselective intermolecular Reformatsky reaction and an intramolecular carbonyl-ene cyclization. In particular, the second strategy through the intramolecular carbonyl-ene reaction led to the formation of a key intermediate 3 in a short and highly stereoselective way, which has allowed for practical and convenient preparation of analogues 2. Using this protocol, we could obtain 22 new mibefradil analogues 2, which were biologically tested for in vitro efficacies against T-type calcium channels and metabolic stabilities. Among the synthesized compounds, we found that analogue 2aa containing a dihydrobenzopyran ring and a secondary amine linker showed high % remaining activities of the tested CYP enzymes retaining the excellent T-type calcium channel blocking activity. These findings indicated that the structural modification of 1 was effective for improving in vitro stability, i.e., reducing CYP inhibition and metabolic degradation.

Background: The PPAR α and PPAR γ are the key messengers responsible for the translation of nutritional stimuli into changes for the expression of genes, particularly genes involved in lipid metabolism. However, the associations between PPAR α/γ polymorphisms and lipid serum levels in the general population were rarely studied, and the conclusions were conflicting. The objective was to investigate the associations of the PPAR α and PPAR γ polymorphisms with dyslipidemia., Methods: 820 subjects were randomly selected from the Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province cohort populations. The logistic regression model was used to examine the association between these polymorphisms and dyslipidemia. SNPstats was used to explore the haplotype association analyses., Results: In the codominant and log-additive models, rs1800206, rs1805192 and rs3856806 were all associated with dyslipidemia (P < 0.005). When the most common haplotype L-G (established by rs1800206, rs4253778) was treated as the reference group, the V-G haplotype was associated with dyslipidemia (P < 0.001), higher TC and TG levels (P < 0.01). Moreover, when compared to Pro-C haplotype (established by rs1805192, rs3856806), the Pro-T, Ala-C, Ala-T haplotypes were associated with dyslipidemia (p < 0.001). A-T haplotype was associated with higher TC levels, (p < 0.01), and the P-T, A-C, A-T haplotypes were associated with higher TG levels (p < 0.01)., Conclusions: PPAR α and PPAR γ polymorphisms and haplotypes may be the genetic risk factors for dyslipidemia.

Background: Visfatin, a proinflammatory mediator, has been associated with poor clinical outcomes after acute brain injury. The present study is designed to investigate the potential association between plasma visfatin levels and the risk of hematoma growth (HG) and early neurologic deterioration (END) after intracerebral hemorrhage., Methods: There were 85 patients as cases who presented with first-time hemorrhagic stroke that were assessed within 6h after the incident. The control group consisted of 85 healthy volunteers. HG was defined as hematoma enlargement >33% at 24h. END was defined as an increase of ≥ 4 points in National Institute of Health Stroke Scale score at 24h from symptoms onset. Plasma visfatin levels were determined using enzyme immunoassay., Results: Plasma visfatin levels were significantly higher in patients compared to controls. Plasma visfatin level emerged as an independent predictor of HG [odds ratio (OR), 1.154; 95% confidence interval (CI), 1.046-3.108; P=0.009] and END (OR, 1.195; 95% CI, 1.073-3.516; P=0.005). For predicting HG, area under curve (AUC) of plasma visfatin level (0.814; 95% CI: 0.715-0.890) was similar to that of hematoma volume (0.839; 95% CI, 0.743-0.909) (P=0.703). For predicting END, AUC of plasma visfatin level (0.828; 95% CI: 0.730-0.901) was similar to that of hematoma volume (0.863; 95% CI, 0.771-0.928) (P=0.605). Visfatin did not improve AUC of hematoma volume for predicting HG and END (both P>0.05)., Conclusion: Plasma visfatin level represents a novel biomarker for predicting HG and END., (© 2013 Elsevier B.V. All rights reserved.)

Objective: To explore the roles of peroxisome proliferator-activated receptors (PPARs) on the levels of serum C-reactive protein(CRP)and the interactions of PPARs haplotypes with abnormal body weight., Methods: Subjects(n = 644)were randomly selected from the cohort 'Prevention of Multiple metabolic disorders and Metabolic syndrome in Jiangsu province(PMMJS)' Variance test, t test and lineal regression were used to analyze the associations between PPARs polymorphisms and the levels of CRP. The association between PPARs haplotypes and serum CRP levels as well as the interaction of PPARs haplotypes with abnormal body weight were analyzed, under the SNPStats software., Results: After adjusting for sex, age, blood pressure, cigarette smoking, alcohol drinking and so on, data showed that both rs1800206 and rs9794 were associated with the changes along with the levels of CRP (P < 0.05). After adjusting for the same factors, haplotypes of AVG and CVG in PPARα, CG in PPARd appeared to be associated with the increase (P < 0.05)while haplotypes of CC in PPARδ, CPCAC in PPARγ were associated with the decrease of CRP levels (P < 0.05). Results from the Interaction analysis also noted that the interactions did exist between abnormal body weight and both AVG, CVG in PPARα, and CG in PPARδ., Conclusion: PPARs polymorphisms and haplotypes were associated with CRP. Interaction between PPAR a/d and abnormal body weight might contribute to the levels of CRP.

Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor involved in the regulation of several biochemical pathways. Blood pressure-lowering effects have been found in PPARγ agonists in several hypertensive models. The biology and research data related to the gene suggest that it could play a role in essential hypertension (EH) susceptibility. This study aimed to investigate the association between PPARγ polymorphisms and EH. About 820 subjects were genotyped for the three single-nucleotide polymorphisms used as genetic markers for the PPARγ genes (C681G, Prol2Ala, and C1431T). After correction for age, sex, smoking, alcohol consumption, body mass index, waist circumference, and fasting glucose, the G allele (CG+GG) of C681G was significantly associated with the increase in the risk of EH (odds ratio [OR]=1.54, 95%confidence interval [CI]: 1.14-2.09, p=0.005). The A allele (PA+PP) of Pro12Ala was significantly associated with the decrease in the risk of EH (OR=0.70, 95%CI: 0.52-0.95, p=0.020). However, C1431T was not significantly associated with EH. Generalized multifactor dimensionality reduction analysis showed that there was a potential gene-gene interaction between C681G and Prol2Ala (p=0.0107). The G-P haplotype (established by C681G, Prol2Ala) was significantly associated with increase in the risk of EH (OR=1.53, 95%CI:1.13-2.07, p=0.006). In conclusion, PPARγ polymorphisms and haplotypes were significantly associated with hypertension susceptibility.

The peroxisome proliferator-activated receptors (PPARs)-α,-β/δ and -γ are the ligand-activated transcription factors that function as the master regulators of glucose, fatty acid and lipoprotein metabolism, energy balance, cell proliferation and differentiation, inflammation and atherosclerosis. This study examined the main effects of both single-locus and multilocus interactions among genetic variants in Chinese Han individuals to test the hypothesis that PPAR-α/δ/γ polymorphisms may contribute to the etiology of hypertriglyceridemia independently and/or through such complex interactions. We genotyped 9 single nucleotide polymorphisms for PPAR-α/δ/γ. Participants were recruited from the Prevention of MetS and Multi-metabolic Disorders in Jiangsu Province of China Study. 820 subjects (474 non-hypertriglyceridemia subjects, 346 hypertriglyceridemia subjects) were randomly selected. Single-locus analyses showed that after adjusted for age, sex, smoking, alcohol consumption, body mass index, waist circumference and fasting glucose, rs1800206, rs9794, rs3856806 and rs1805192 were significantly associated with hypertriglyceridemia, the OR (95% CI) were 4.43(3.08-6.37), 1.49(1.10-2.02), 1.56(1.16-2.08), 2.43(1.80-3.29), respectively. Further, generalized multifactor dimensionality reduction method analysis showed that two-to-six-locus and eight-locus models were significant (p<0.05), which indicated a potential gene-gene interaction among PPAR-α/δ/γ polymorphisms. The results suggest that PPAR-α/δ/γ polymorphisms may contribute to the risk of hypertriglyceridemia independently and/or in an interactive manner., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To investigate the association of ten single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors (α, δ, γ) with low high-density lipoprotein-cholesterol (HDL-C) hyperlipidemia and the additional role of a gene-gene interactions among the 10 SNPs., Methods: Participants were recruited under the framework of the PMMJS (Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province) cohort populations survey, in the urban community of Jiangsu province, China. 820 subjects (579 normal HDL-C, 241 low HDL-C) were randomly selected, with one of them related to each other. Ten SNPs (rs135539, rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806, rs4684847) were selected from the HapMap database, which covered PPARα, PPARδ and PPARγ. Logistic regression model was used to examine the association between ten SNPs in the PPARs and low HDL-C. Odds ratios (OR) and 95% confident interval (95%CI) were calculated. Interactions were explored by using the method of Generalized Multifactor Dimensionality Reduction (GMDR)., Results: After adjusting the factors as age, sex, smoking status, occupational physical activity, high-fat diet as well as low-fiber diet, both rs135539 and rs1800206 were significantly associated with the incidence of low HDL-C, with the OR (95% CI) values as 1.46 (1.07 - 1.99) and 0.62 (0.42 - 0.90). No statistically significant difference was found between other SNPs and the occurrence of low HDL-C. Data from GMDR analysis showed significant gene-gene interaction among rs135539, rs4253778 of PPARα and rs10865710, rs3856806, rs709158 and rs4684847 of PPAR γ (P = 0.0107)., Conclusion: PPARα rs135539 was associated with the occurrence of low HDL-C, and had interacted with rs4253778, rs10865710, rs3856806, rs709158 and rs4684847.

Objective: To investigate the association of ten SNP at peroxisome proliferator-activated receptors (PPARα, δ, γ) with hypertriglyceridemia and the gene-gene interaction., Methods: Participants were recruited from the Prevention of MetS and Multi-metabolic Disorders in Jiangsu province of China Study (PMMJS). A total of 820 subjects were selected from the 4083 participants who had received follow-up examination, by using simple random sampling. Participants in baseline and follow-up study surveys were both collected blood samples 11 ml in the morning after at least 8 hours of fasting. Blood samples which collected at the baseline were subjected to PPARα, PPARδ and PPARγ genotype analyses. Blood samples which collected at the follow-up were used to measure serum triglyceride levels. The logistic regression model was used to analyze the association between different SNP and hypertriglyceridemia, and the generalized multifactor dimensionality reduction (GMDR) was applied to explore the gene-gene interaction., Results: The samples included 474 in the non-hypertriglyceridemia group and 346 in the hypertriglyceridemia group. The genotype frequencies of rs1800206 in the hypertriglyceridemia group were 211 (61.0%) for LL, 132 (38.2%) for LV and 3 (0.9%) for VV, and in the non-hypertriglyceridemia group were 411 (86.7%) for LL, 59 (12.4%) for LV and 4(0.8%) for VV (χ(2) = 74.18, P < 0.01). V allele frequencies of rs1800206 in the hypertriglyceridemia group was 138(19.9%), and in the non-hypertriglyceridemia group was 67 (7.1%) (χ(2) = 60.62, P < 0.01). The genotype frequencies of rs2016520 in the hypertriglyceridemia group were 177 (51.2%) for TT, 154 (44.5%) for TC and 15 (4.3%) for CC, and in the non-hypertriglyceridemia group were 211 (44.5%) for TT, 212 (44.7%) for TC and 51 (10.8%) for CC(χ(2) = 15.93, P < 0.01). C allele frequencies of rs2016520 in the hypertriglyceridemia group was 184(26.6%), and in the non-hypertriglyceridemia group was 314 (33.1%) (χ(2) = 8.07, P < 0.01). The genotype frequencies of rs3856806 in the hypertriglyceridemia group were 149 (43.1%) for CC, 156 (45.1%) for CT and 41 (11.8%) for TT, and in the non-hypertriglyceridemia group were 269 (56.8%) for CC, 170 (35.9%) for CT and 35 (7.4%) for TT (χ(2) = 15.93, P < 0.01). T allele frequencies of rs3856806 in the hypertriglyceridemia group was 238(34.4%), and was 240 (25.3%) in the non-hypertriglyceridemia group (χ(2) = 15.96, P < 0.01). The genotype frequencies of rs1805192 in the hypertriglyceridemia group were 145 (41.9%) for PP, 158(45.7%) for PA and 43(12.4%) for AA, and in the non-hypertriglyceridemia group were 314 (66.2%) for PP, 137(28.9%) for PA and 23(4.9%) for AA (χ(2) = 50.92, P < 0.01). A allele frequencies of rs1805192 in the hypertriglyceridemia group was 244(35.2%), and was 183 (19.3%) in the non-hypertriglyceridemia group(χ(2) = 52.89, P < 0.01). After adjusting age, gender, smoking, alcohol consumption, high-fat diet, low -fiber diet and occupational physical activity factors, rs1800206, rs2016520, rs3856806 and rs1805192 were significantly associated with hypertriglyceride, while the OR (95%CI) was 3.88 (2.69 - 5.60), 0.71 (0.52 - 0.96), 1.40 (1.03 - 1.90) and 2.56 (1.88 - 3.49), respectively (P < 0.05). GMDR model analysis showed that the second-order model (rs1800206 and rs1805192) was the best model when quality traits of triglyceride was chosen as outcome (P < 0.01); while third-order model (rs1800206, rs1805192 and rs2016520) was the best model when quantitative traits of triglyceride was chosen as outcome (P < 0.01)., Conclusion: The rs1800206, rs2016520, rs3856806 and rs1805192 were significantly associated with hypertriglyceridemia. There was a gene-gene interaction between multiple SNP.

Objective: To investigate the association between ten single nucleotide polymorphism (SNP) in the peroxisome proliferator-activated receptor (PPAR) α/δ/γ and essential hypertension (EH)., Methods: Participants were recruited within the framework of a cohort populations survey from the PMMJS (Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province) which was conducted in the urban community of Jiangsu province from 1999 to 2007. Eight hundred and twenty subjects (551 non-hypertensive subjects, 269 hypertensive subjects) were randomly selected but were not related to each other. Ten SNP (rs135539, rs1800206, rs4253778 of PPARα; rs2016520, rs9794 of PPARδ; rs10865710, rs1805192, rs4684847, rs709158 and rs3856806 of PPARγ) were selected from the HapMap database. χ(2) test was used to determine whether the whole population was in H-W genetic equilibrium. SHEsis software was used to examine the relations of SNP and linkage equilibrium. Logistic regression model was used to examine the association between ten SNP in the PPAR and EH., Results: Difference on the distribution of four SNP genotypes including rs1800206, rs9794, rs10865710 and rs4684847 between high blood pressure and non-high blood pressure group, high systolic blood pressure (SBP) and normal SBP group, high diastolic blood pressure (DBP) and normal DBP group was significant (P < 0.05). After adjusting factors as age, sex, body mass index, fasting plasma glucose, high density lipoprotein cholesterol-C, high-fat diet and compared with wild-type gene carriers, the OR (95%CI) of objects with rs1800206 V allele appeared in high blood pressure, high SBP and high DBP were 0.60 (0.41 - 0.89), 0.57 (0.37 - 0.88) and 0.61 (0.39 - 0.96), respectively. The OR (95%CI) of objects with G allele of rs9794 were 0.63 (0.46 - 0.87), 0.51 (0.36 - 0.73) and 0.68 (0.47 - 1.01). The OR (95%CI) of objects with G allele of rs10865710 were 1.62 (1.19 - 2.20), 1.59 (1.14 - 2.22) and 1.53 (1.07 - 2.18), respectively. While the OR (95%CI) of objects with rs4684847 T allele were 1.42 (1.04 - 1.94), 1.38 (1.03 - 1.92) and 1.37 (1.00 - 1.88), respectively., Conclusion: The four SNPs including rs1800206 of PPARα, rs9794 of PPARδ and rs4684847, rs10865710 of PPARγ influenced high blood pressure, high SBP and high DBP to different degrees.

Objective: To investigate the value of spiral CT examination for diagnosis occult fracture of the patients with negative result of X-ray examination and with high suspicion of fractures,so as to reduce misdiagnosis., Methods: From January 2007 to June 2010, 31 patients with ankle trauma performed spiral CT examination, including 18 males and 13 females, ranging in age from 21 to 67 years, with a mean of 35 years. The main symptoms of the patients included ankle pain, local swelling, obvious tenderness and activity limitation. All the patients had negative results of X-ray examination., Results: The spiral CT examination revealed 11 patients with fractures, involving a total of 17 points. Single fracture were found in 6 cases,and multiple fractures were found in 5 cases. Among single fractures, the lateral malleolus fracture was found in 1 case, talus fracture was found in 1 case, scaphoid fracture was found in 1 case, the fracture of the base of 5th metatarsal base was found in 1 case and calcaneal fractures were found in 2 cases. Within multiple fractures,internal and lateral malleolus fracture were found in 1 case; medial malleolus, calcaneus and talus fractures were found in 1 case; talus and scaphoid fractures were found in 1 case; the fractures of 1st and 2nd cuneiform bone were found in 1 case; the 2nd and 3rd metatarsal base fracture was found in 1 case., Conclusion: For the patients with negative X-ray examination and high suspicion of fractures,the spiral CT examination is needed, which could significantly improve the detection rate of occult fractures, and provide imaging basis for clinical treatment and judicial identify.

We have synthesized and biologically evaluated 1,4-diazepane derivatives as T-type calcium channel blockers. In this study, we discovered compound 4s, a potential T-type calcium channel blocker with good selectivity over hERG and N-type calcium channels. In addition, it exhibited favorable pharmacokinetic characteristics for further investigation of T-type calcium channel related diseases., (2010 Elsevier Ltd. All rights reserved.)

We study the fidelity susceptibility in the two-dimensional (2D) transverse-field Ising model and the 2D XXZ model numerically. It is found that in both models, the fidelity susceptibility as a function of the driving parameter diverges at the critical points. The validity of the fidelity susceptibility to signal for the quantum phase transition is thus verified in these two models. We also compare the scaling behavior of the extremum of the fidelity susceptibility to that of the second derivative of the ground-state energy. From those results, the theoretical argument that fidelity susceptibility is a more sensitive seeker for a second-order quantum phase transition is also testified in the two models.

We study the reduced fidelity susceptibility chi(r) for an M -body subsystem of an N -body Lipkin-Meshkov-Glick model with tau=M/N fixed. The reduced fidelity susceptibility can be viewed as the response of subsystem to a certain parameter. In noncritical region, the inner correlation of the system is weak, and chi(r) behaves similar with the global fidelity susceptibility chi(g), the ratio eta=chi(r)/chi(g) depends on tau but not on N. However, at the critical point, the inner correlation tends to be divergent, and we find chi(r) approaches chi(g) with increasing the N. It is interesting to note that, eta=1 in the thermodynamic limit, which means the susceptibilities of the local and global system are the same. Finally, we make numerical computations, and they are in perfect agreement with the analytical predictions.

In this work, we examine the validity of quantum adiabatic theorem in thermodynamic systems. For a d-dimensional quantum many-body system, we show that the duration time tau0 required by its ground-state adiabatic process does not depend on the microscopic details but the scaling dimension of the fidelity susceptibility da. Our result, therefore, provides a quantitative time scale of the quantum adiabatic theorem in thermodynamic systems. The quantum adiabatic theorem might be violated in case that the scaling dimension of the fidelity susceptibility is larger than the system's real dimension (da>d).

We study the critical properties of the Lipkin-Meshkov-Glick model in terms of the fidelity susceptibility. By using the Holstein-Primakoff transformation, we obtain explicitly the critical exponent of the fidelity susceptibility around the second-order quantum phase transition point. Our results provide a rare analytic case for the fidelity susceptibility in describing the universality class in quantum critical behavior. The different critical exponents in two phases are nontrivial results, indicating that the fidelity susceptibility is not always extensive.