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Peng-Yu Chen,1 Minxue Shen,2– 4 Sui-Qing Cai,1 Zhen-Wei Tang1 1Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of China; 2Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 3Hunan Engineering Research Center of Skin Health and Disease; Hunan Key Laboratory of Skin Cancer and Psoriasis (Xiangya Hospital), Changsha, 410008, People’s Republic of China; 4Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, 410078, People’s Republic of ChinaCorrespondence: Zhen-Wei Tang; Sui-Qing Cai, Email tangzhenwei@zju.edu.cn; 2191008@zju.edu.cnAbstract: As one of the most prevalent chronic inflammatory skin diseases, atopic dermatitis (AD) increasingly affects the aging population. Amid the ongoing global aging trend, it’s essential to recognize the intricate relationship between AD and aging. This paper reviews existing knowledge, summarizing clinical observations of associations between AD and aging-related diseases in various systems, including endocrine, cardiovascular, and neurological. Additionally, it discusses major theories explaining the correlation, encompassing skin-mucosal barriers, systemic inflammation and stress, genes, signal transduction, and environmental and behavioral factors. The association between AD and aging holds significant importance, both in population and basic perspectives. While further research is warranted, this paper aims to inspire deeper exploration of inflammation/allergy-aging dynamics and the timely management of elderly patients with AD.Keywords: atopic dermatitis, aging, age-related diseases, clinical observations, mechanical theories

Xian-Qi Zhang,* Zhen-Wei Tang,* Jing Jing Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Jing, Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of China, Tel +86 571 87784558, Fax +86 571 87783504, Email haitong1987@163.comAbstract: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by rapidly developing and painful skin ulcers with distinctive features. As far as we are concerned, there is no previous case report on facial PG in East-Asia. In this case, we describe a case of a 79-year-old man with a 3-month history of progressive painful ulcers on his cheek and upper lip. Initial suspicion of atypical mycobacterium infection led to an ineffective treatment regimen. Comprehensive infectious testing yielded negative results, and a positive pathergy test indicated a potential diagnosis of PG. A skin biopsy confirmed the diagnosis, and the patient showed significant improvement with intravenous methylprednisolone and oral cyclosporine treatment. After three months, complete resolution of the lesions was achieved without recurrence. The case highlights the diagnostic challenges associated with PG, which is often misdiagnosed due to its resemblance to other conditions. Thorough evaluation is crucial to exclude alternative diagnoses, particularly cutaneous infections. Clinical morphology, tissue biopsy, and culture are essential for accurate diagnosis. The presence of pathergy, the development of new lesions following minor trauma, can also be a diagnostic clue.Keywords: Pyoderma gangrenosum, neutrophilic dermatosis, ulcer

Hui Ding,1 Fen Yan,1 Lin-Lin Zhou,2 Xiu-Hai Ji,3 Xin-Nan Gu,1 Zhi-Wei Tang,1 Ru-Hua Chen11Department of Pulmonary Medicine, The Affiliated Yixing People's Hospital, Jiangsu University, Zhenjiang, Jiangsu Province, 2Department of Cardiology, Affiliated Cixi Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, 3Department of Oncology, Affiliated Taicang Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu Province, People's Republic of ChinaPurpose: To replicate previously confirmed telomere-length loci in a Chinese Han population with coronary heart disease (CHD), and investigate these loci and the possibility of and age at onset of CHD.Patients and methods: 1514 CHD patients and 2470 normal controls were recruited. Medical data including age, sex, body mass index, lipid profiles, history of hypertension, type 2 diabetes mellitus, and dyslipidemia were collected from all the participants. Seven previously identified single-nucleotide polymorphisms (SNPs) related to leucocyte telomere length were genotyped, including rs10936599 in TERC, rs2736100 in TERT, rs7675998 in NAF1, rs9420907 in OBFC1, rs8105767 in ZNF208, rs755017 in RTEL1, and rs11125529 in ACYP2.Results: No significant difference in genotype frequencies from the Hardy–Weinberg equilibrium test was noted for all tested SNPs both in the CHD patients and the normal controls. No polymorphism was observed for rs9420907, and AA genotype was noted in both the CHD patients and the controls. Neither the genotype nor the allele frequencies of rs2736100, rs8105767, rs11125529, and rs2967374 were significantly different between the CHD patients and the normal controls. For rs10936599 and rs755017, statistical difference was found for the allele frequency but not genotype. Distributions of genotype and allele were significantly different between the two groups for rs7675998. The odds ratio for carriers of CHD was 2.127 (95% confidence interval: 1.909–2.370) for the A allele of rs7675998. By one-way analysis of variance test, rs7675998 was associated with the onset age of CHD. CHD patients with the AA genotype of rs7675998 had significantly lower onset age (P

The growing incidence of Clostridium difficile associated diarrhea (CDAD) underscores the urgency for potent treatments. This research delves into the therapeutic potential of Scutellaria baicalensis Georgi (Lamiaceae) root (SR) in addressing CDAD and its influence on gut microbiota. Using a CDAD mouse model and fidaxomicin as a control, SR's impact was measured through diarrhea symptoms, colonic histopathology, and C. difficile toxin levels. Employing the PacBio platform, 16S rRNA full-length gene sequencing analyzed the gut microbial composition and the effect of SR. Results revealed SR considerably alleviated diarrhea during treatment and restoration phases, with a marked decrease in colonic inflammation. C. difficile toxin levels dropped significantly with SR treatment (P < 0.001). While SR didn't augment gut microbiota's overall abundance, it enhanced its diversity. It restored levels of Proteobacteria and Bacteroidetes, reduced Akkermansia spp. and Enterococcus spp. proportions, and modulated specific bacterial species' abundance. In essence, SR effectively mitigates CDAD symptoms, curtails inflammatory reactions, and beneficially restructures gut microbiota, suggesting its potential in advanced CDAD clinical intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known financial or interpersonal conflicts that might have looked to have influenced the research presented in this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Early identification of patients at high risk of operative mortality is important for acute type A aortic dissection (TAAD). We aimed to investigate whether patients with distinct risk stratifications respond differently to anti-inflammatory pharmacotherapy., Methods: From 13 cardiovascular hospitals, 3110 surgically repaired TAAD patients were randomly divided into a training set (70%) and a test set (30%) to develop and validate a risk model to predict operative mortality using extreme gradient boosting. Performance was measured by the area under the receiver operating characteristic curve (AUC). Subgroup analyses were performed by risk stratifications (low versus middle-high risk) and anti-inflammatory pharmacotherapy (absence versus presence of ulinastatin use)., Results: A simplified risk model was developed for predicting operative mortality, consisting of the top ten features of importance: platelet-leukocyte ratio, D-dimer, activated partial thromboplastin time, urea nitrogen, glucose, lactate, base excess, hemoglobin, albumin, and creatine kinase-MB, which displayed a superior discrimination ability (AUC: 0.943, 95 % CI 0.928-0.958 and 0.884, 95 % CI 0.836-0.932) in the derivation and validation cohorts, respectively. Ulinastatin use was not associated with decreased risk of operative mortality among each risk stratification, however, ulinastatin use was associated with a shorter mechanical ventilation duration among patients with middle-high risk (defined as risk probability >5.0 %) (β -1.6 h, 95 % CI [-3.1, -0.1] hours; P = 0.048)., Conclusion: This risk model reflecting inflammatory, coagulation, and metabolic pathways achieved acceptable predictive performances of operative mortality following TAAD surgery, which will contribute to individualized anti-inflammatory pharmacotherapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

In children with asymmetric growth on the medial and lateral side of limbs, if there still remains growth potential, the guided growth technique of hemi-epiphysiodesis on one side of the epiphysis is recognized as a safe and effective method. However, when the hemi-epiphysiodesis start to correct the deformities, how many degrees could hemi-epiphysiodesis bring every month and when to remove the hemi-epiphysiodesis implant without rebound phenomenon are still on debate. This article reviews the current studies focus on the effective time, correction speed and termination time of hemi-epiphysiodesis., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Association of distinct inflammatory profiles with short-term mortality is little known in type A aortic dissection (TAAD). Latent class analysis was used to identify distinct inflammatory profiles based on leukocyte, neutrophils, monocyte, lymphocytes, platelet, fibrinogen, D-dimer, neutrophils-lymphocyte ratio, platelet-lymphocyte ratio, and lymphocyte-monocyte ratio. We identified 193 patients with median age of 56 (IQR 47-63) years and 146 males. Patients were divided as hyper-inflammatory profiles (84 [43.5%]) and hypo-inflammatory profiles (109 [56.5%]). Although baseline characteristics were not different, hyper-inflammatory patients had higher 6-month mortality (20 [23.8%] vs. 11 [10.1%]; P = 0.014) and 30-day mortality (18 [21.4%] vs. 9 [8.3%], P = 0.009) than hypo-inflammatory patients. After adjustment for potential confounders, hyper-inflammatory profiles remain associated with higher risk of 6-month mortality than hypo-inflammatory profiles (adjusted OR 2.427 [95%CI 1.154, 5.105], P = 0.019). Assessment of preoperative inflammatory profiles adds clarity regarding the extent of inflammatory response to TAAD aetiopathologies, highlighting individual anti-inflammatory pharmacotherapy for TAAD. ClinicalTrials.gov Identifier: NCT04398992., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Breast cancer is the most common malignancy in women worldwide. Triple-negative breast cancer (TNBC), refers breast cancer negative for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, characterized by high drug resistance, high metastasis and high recurrence, treatment of which is a difficult problem in the clinical treatment of breast cancer. In order to better treat TNBC clinically, it is a very urgent task to explore the mechanism of TNBC resistance in basic breast cancer research. Pregnane X receptor (PXR) is a nuclear receptor whose main biological function is to participate in the metabolism, transport and clearance of allobiological agents in PXR. PXR plays an important role in drug metabolism and clearance, and PXR is highly expressed in tumor tissues of TNBC patients, which is related to the prognosis of breast cancer patients. This reviews synthesized the important role of PXR in the process of high drug resistance to TNBC chemotherapeutic drugs and related research progress., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Few articles have reported on the treatment of Masada type 2 forearm deformities in hereditary multiple exostosis, possibly because of the high redislocation rate and other complications. This study precisely declares the use of modified ulnar lengthening by an Ilizarov external fixation with tumour excision for the treatment of Masada type 2 forearm deformities. 20 children with Masada type 2 forearm deformities were admitted for surgical treatment at our hospital from February 2014 to February 2021. There were 13 girls and 7 boys, ranging in age from 3.5 to 15 years (mean: 9 years) at the time of operation. We removed the prominent osteochondromas of the distal ulna and the proximal radius, positioned a classic Ilizarov external fixator on the forearm and then performed ulnar transverse one-third proximal diaphyseal subperiosteal osteotomy. We adopted modified ulnar lengthening postoperatively. The effects of surgical correction of deformity and functional improvement of the limb were assessed via regular follow-up and X-ray. The patients were followed up for 36 months, and the ulna was lengthened 26.99 mm on average; all radial heads remained relocated. The radiographic evaluations, including relative ulnar shortening, radial articular angle, and carpal slip, were improved. The functions of the elbow and forearm were all improved after surgery. Modified ulnar lengthening by an Ilizarov external fixation with tumour excision for the treatment of Masada type 2 forearm deformities in hereditary multiple exostoses has been proven to be an effective and reliable technique in the early stage., (© 2023. The Author(s).)

Background: The effectiveness of Platelet-Rich Plasma (PRP) in the treatment of patients with Achilles tendon rupture (ATR) and Achilles tendinopathy (AT) has been controversial., Aim: To assess PRP injections' effectiveness in treating ATR and AT., Methods: A comprehensive review of relevant literature was conducted utilizing multiple databases such as Cochrane Library, PubMed, Web of Science, Chinese Science and Technology Journal, EMBASE, and China Biomedical CD-ROM. The present investigation integrated randomized controlled trials that assessed the effectiveness of platelet-rich plasma injections in managing individuals with Achilles tendon rupture and tendinopathy. The eligibility criteria for the trials encompassed publications that were published within the timeframe of January 1, 1966 to December 2022. The statistical analysis was performed utilizing the Review Manager 5.4.1, the visual analogue scale (VAS), Victorian Institute Ankle Function Scale (VISA-A), and Achilles Tendon Thickness were used to assess outcomes., Results: This meta-analysis included 13 randomized controlled trials, 8 of which were randomized controlled trials of PRP for AT and 5 of which were randomized controlled trials of PRP for ATR. PRP for AT at 6 wk [weighted mean difference (WMD) = 1.92, 95%CI: -0.54 to 4.38, I 2 = 34%], at 3 mo [WMD = 0.20, 95%CI: -2.65 to 3.05, I 2 = 60%], and 6 mo [WMD = 2.75, 95%CI: -2.76 to 8.26, I 2 = 87%) after which there was no significant difference in VISA-A scores between the PRP and control groups. There was no significant difference in VAS scores between the PRP group and the control group after 6 wk [WMD = 6.75, 95%CI: -6.12 to 19.62, I 2 = 69%] and 6 mo [WMD = 10.46, 95%CI: -2.44 to 23.37, I 2 = 69%] of treatment, and at mid-treatment at 3 mo [WMD = 11.30, 95%CI: 7.33 to 15.27, I 2 = 0%] after mid-treatment, the PRP group demonstrated better outcomes than the control group. Post-treatment patient satisfaction [WMD = 1.07, 95%CI: 0.84 to 1.35, I 2 = 0%], Achilles tendon thickness [WMD = 0.34, 95%CI: -0.04 to 0.71, I 2 = 61%] and return to sport [WMD = 1.11, 95%CI: 0.87 to 1.42, I 2 = 0%] were not significantly different between the PRP and control groups. The study did not find any statistically significant distinction between the groups that received PRP treatment and those that did not, regarding the Victorian Institute of Sport Assessment - Achilles scores at 3 mo [WMD = -1.49, 95%CI: -5.24 to 2.25, I 2 = 0%], 6 mo [WMD = -0.24, 95%CI: -3.80 to 3.32, I 2 = 0%], and 12 mo [WMD = -2.02, 95%CI: -5.34 to 1.29, I 2 = 87%] for ATR patients. Additionally, no significant difference was observed between the PRP and the control groups in improving Heel lift height respectively at 6 mo [WMD = -3.96, 95%CI: -8.61 to 0.69, I 2 = 0%] and 12 mo [WMD = -1.66, 95%CI: -11.15 to 7.83, I 2 = 0%] for ATR patients. There was no significant difference in calf circumference between the PRP group and the control group after 6 mo [WMD = 1.01, 95%CI: -0.78 to 2.80, I 2 = 54%] and 12 mo [WMD = -0.55, 95%CI: -2.2 to 1.09, I 2 = 0%] of treatment. There was no significant difference in ankle mobility between the PRP and control groups at 6 mo of treatment [WMD = -0.38, 95%CI: -2.34 to 1.58, I 2 = 82%] and after 12 mo of treatment [WMD = -0.98, 95%CI: -1.41 to -0.56, I 2 = 10%] there was a significant improvement in ankle mobility between the PRP and control groups. There was no significant difference in the rate of return to exercise after treatment [WMD = 1.20, 95%CI: 0.77 to 1.87, I 2 = 0%] and the rate of adverse events [WMD = 0.85, 95%CI: 0.50 to 1.45, I 2 = 0%] between the PRP group and the control group., Conclusion: The use of PRP for AT improved the patient's immediate VAS scores but not VISA-A scores, changes in Achilles tendon thickness, patient satisfaction, or return to sport. Treatment of ATR with PRP injections alone improved long-term ankle mobility but had no significant effect on VISA-A scores, single heel lift height, calf circumference or return to sport. Additional research employing more extensive sampling sizes, more strict experimental methods, and standard methodologies may be necessary to yield more dependable and precise findings., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: To describe the demographics and phenotypes of malignancies-associated dermatomyositis (MADM) in east China and pinpoint potential factors indicative of malignancies in patients with dermatomyositis and establish a predictive model., Methods: We retrospectively analyzed clinical data from 134 patients with adult-onset dermatomyositis hospitalized between January 2019 and May 2022 in one comprehensive hospital. Clinical data including disease course, initial symptoms and signs, and demographic information were retrieved from the Electronic Medical Records System. Other parameters including myositis-specific autoantibodies profiles, ferritin, sedimentation, etc. were all referable. Multivariable multinomial logistic regression was employed to simulate a model to predict cancer risks. Receiver operating characteristic curve was adopted to evaluate the potency of the model., Results: 134 patients with adult-onset dermatomyositis were aptly enrolled in this study based on inclusive and exclusive criteria: 12 (8.96%) with malignancies, 57 (42.53%) with aberrant tumor biomarkers but no malignancies, 65 (48.51%) with neither malignancies nor abnormal tumor biomarkers. Senior diagnostic age, higher LDH, higher ferritin, positive anti-TIF1γ and anti-Mi2 rather than anti-NXP2 autoantibodies were positive indicators of malignancies. Additionally, neither initial complaints nor signs were found to be correlated to a tendency towards malignancies. Digestive system, nasopharyngeal, and lung malignancies were mostly documented in east China. One multivariable multinomial logistic regression model was established to predict the phenotypes of dermatomyositis on the basis of potential malignancies and the overall sensitivity and specificity was satisfactory., Conclusion: Positivity of anti-TIF1γ and anti-Mi2 autoantibodies are highly indicative of malignancies while the role of anti-NXP2 autoantibody in MADM in the Chinese population remains unclear. The phenotypes of malignancies can be predicted through the model and the predictive power is sufficient. More attention should be paid to malignancies screening in patients with aberrant tumor biomarkers but no malignancies, particularly digestive system, nasopharyngeal, and lung malignancies in patients with dermatomyositis but without malignancies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tang, Chi, Tang, Li and Man.)

Background: JAK inhibitors treat various autoimmune diseases, but an updated systematic review in treating alopecia areata is currently lacking., Objective: Evaluate the specific efficacy and safety of JAK inhibitors in alopecia areata by systematic review and meta-analysis., Methods: Eligible studies in PubMed, Embase, Web of Science, and Clinical Trials up to May 30, 2022, were searched. We enrolled in randomized controlled trials and observational studies of applying JAK inhibitors in alopecia areata., Results: 6 randomized controlled trials with 1455 patients exhibited SALT 50 (odd ratio [OR], 5.08; 95% confidence interval [CI], 3.49-7.38), SALT 90 (OR, 7.40; 95% CI, 4.34-12.67) and change in SALT score (weighted mean difference [WSD], 5.55; 95% CI, 2.60-8.50) compared to the placebo. The proportion of 26 observational studies with 563 patients of SALT 5 was 0.71(95% CI, 0.65-0.78), SALT 50 was 0.54(95% CI 0.46-0.63), SALT 90 was 0.33(95% CI, 0.24-0.42), and SALT score (WSD, -2.18; 95% CI, -3.12 to -1.23) compared with baseline. Any adverse effects occurred in 921 of 1508 patients; a total of 30 patients discontinued the trial owing to adverse reactions., Limitations: Few randomized controlled trials met the inclusion criteria and insufficiency of eligible data., Conclusion: JAK inhibitors are effective in alopecia areata, although associated with an increased risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mao, Ding, Jing, Tang, Miao, Yang, Chen, Chen, Wu and Lu.)

Background: The increase in the number of thyroid cancer cases in recent years has increased not only the medical burden but also the potential for overtreatment. Therefore, it is crucial to distinguish papillary thyroid cancer from benign thyroid nodules before surgery when treating thyroid nodules., Methods: The patients were divided into two groups: 117 patients made up the validation cohort and 414 patients made up the primary cohort. As a result of the primary cohort, a preoperative prediction model was developed, which was then validated externally in the validation cohort. Preoperative thyrotropin (thyroid stimulating hormone, TSH), systemic immune-inflammation index (SII), lymphocyte-to-monocyte ratio (LMR), and ultrasonographic features were recorded in both groups., Results: As predictors for the model, the preoperative blood levels of TSH, SII, LMR, echogenicity, margin, calcification, composition, taller-than-wide, and age were chosen. This was the regression equation: Y = -0.070 × (age) + 1.511 × (echogenicity) + 1.664 × (margin) + 1.003 × (calcification) + 0.939 × (composition) + 2.964 × (tall than wide) + 0.305 × (TSH) + 0.558 × (SII) - 1.271 × (LMR) + 0.327. Papillary thyroid carcinoma (PTC) was predicted positively with values of Y ≥0.808. The prediction model's accuracy, sensitivity, and specificity were 88.2%, 85.1%, and 94.9%, respectively. The area under the receiver operating characteristic (ROC) curve was 0.961. The model's external validation produced satisfactory results with accuracy, sensitivity, and specificity of 85.5%, 90.9%, and 75.5%, respectively., Conclusions: Using the preoperative TSH, SII, LMR, and ultrasonographic characteristics, a straightforward and accurate preoperative prediction model for PTC has been developed and validated. The preoperative assessment of PTC in clinical application is enhanced by this approach., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-2478/coif). The authors have no conflicts of interest to declare., (2023 Translational Cancer Research. All rights reserved.)

Chronic osteomyelitis is a painful and serious disease caused by infected surgical prostheses or infected fractures. Traditional treatment includes surgical debridement followed by prolonged systemic antibiotics. However, excessive antibiotic use has been inducing rapid emergence of antibiotic-resistant bacteria worldwide. Additionally, it is difficult for antibiotics to penetrate internal sites of infection such as bone, thus limiting their efficacy. New approaches to treat chronic osteomyelitis remain a major challenge for orthopedic surgeons. Luckily, the development of nanotechnology has brought new antimicrobial options with high specificity to infection sites, offering a possible way to address these challenges. Substantial progress has been made in constructing antibacterial nanomaterials for treatment of chronic osteomyelitis. Here, we review some current strategies for treatment of chronic osteomyelitis and their underlying mechanisms., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Knowledge is limited regarding the significance of pulmonary arterial pressure (PAP) in predominantly congenital mitral valve regurgitation (MR)-based intracardiac abnormalities., Methods: From a prospective cohort, we included 200 patients with congenital MR regardless of other associated intracardiac abnormalities (mean age 60.4 months, 67% female, systolic PAP (sPAP) 54.2 mm Hg) surgically repaired in 2012-2019 and followed up to 2020 (median 30.0 months). Significant pulmonary hypertension (PH) was defined as sPAP &gt;50 mm Hg at rest or mean PAP &gt;25 mm Hg on right heart catheterization. By perioperative sPAP changes, patients were stratified as group I (pre-normotension to post-normotension), group II (pre-hypertension to post-normotension), or group III (pre-hypertension to post-hypertension). Primary outcomes were the recurrence of MR (defined as the regurgitation grade of moderate or greater) and the progression of MR (defined as any increase in the magnitude of regurgitation grade after surgery). Cox proportional hazard and Kaplan-Meier curve were performed., Results: There was no association between preoperative PH and the recurrent MR (adjusted hazard ratios [aHR]: 1.146 [95% CI: 0.453-2.899]) and progressive MR (aHR: 1.753 [95% CI: 0.807-3.804]), respectively. There were no significant differences among group I, group II, and group III in the recurrent MR but in the progressive MR. A dose dependency was identified for preoperative sPAP with recurrent MR (aHR: 1.050 [95% CI: 1.029-1.071]) and progressive MR risks (aHR: 1.037 [95% CI: 1.019-1.055]), respectively., Conclusions: Preoperative higher sPAP is associated with worse outcomes, warranting heightened attention to the identification of perioperative sPAP., (© 2023 S. Karger AG, Basel.)

Intraoperative seizure is the most prevalent and serious complication of awake craniotomy in functional areas, which may not only trigger complications of the surgical procedure or even the failure of awake craniotomy but also may result in adverse consequences to patients. The influencing factors of intraoperative seizures are unclear, and only the possible influencing factors can be acquired from the examination and summary of existing cases to offer guidance for the seizure prevention of intraoperative epilepsy., (Copyright © 2023. Published by Elsevier Inc.)

Aims: The incremental usefulness of circulating biomarkers from different pathological pathways for predicting mortality has not been evaluated in acute Type A aortic dissection (ATAAD) patients. We aim to develop a risk prediction model and investigate the impact of arch repair strategy on mortality based on distinct risk stratifications., Methods and Results: A total of 3771 ATAAD patients who underwent aortic surgery retrospectively included were randomly divided into training and testing cohorts at a ratio of 7:3 for the development and validation of the risk model based on multiple circulating biomarkers and conventional clinical factors. Extreme gradient boosting was used to generate the risk models. Subgroup analyses were performed by risk stratifications (low vs. middle-high risk) and arch repair strategies (proximal vs. extensive arch repair). Addition of multiple biomarkers to a model with conventional factors fitted an ABC risk model consisting of platelet-leucocyte ratio, mean arterial pressure, albumin, age, creatinine, creatine kinase-MB, haemoglobin, lactate, left ventricular end-diastolic dimension, urea nitrogen, and aspartate aminotransferase, with adequate discrimination ability {area under the receiver operating characteristic curve (AUROC): 0.930 [95% confidence interval (CI) 0.906-0.954] and 0.954, 95% CI (0.930-0.977) in the derivation and validation cohort, respectively}. Compared with proximal arch repair, the extensive repair was associated with similar mortality risk among patients at low risk [odds ratio (OR) 1.838, 95% CI (0.559-6.038); P = 0.316], but associated with higher mortality risk among patients at middle-high risk [OR 2.007, 95% CI (1.460-2.757); P < 0.0001]., Conclusion: In ATAAD patients, the simultaneous addition of circulating biomarkers of inflammatory, cardiac, hepatic, renal, and metabolic abnormalities substantially improved risk stratification and individualized arch repair strategy., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The objective of this study was to apply a machine learning method to evaluate the risk factors associated with serious adverse events (SAEs) and predict the occurrence of SAEs in cancer inpatients using antineoplastic drugs. A retrospective review of the medical records of 499 patients diagnosed with cancer admitted between January 1 and December 31, 2017, was performed. First, the Global Trigger Tool (GTT) was used to actively monitor adverse drug events (ADEs) and SAEs caused by antineoplastic drugs and take the number of positive triggers as an intermediate variable. Subsequently, risk factors with statistical significance were selected by univariate analysis and least absolute shrinkage and selection operator (LASSO) analysis. Finally, using the risk factors after the LASSO analysis as covariates, a nomogram based on a logistic model, extreme gradient boosting (XGBoost), categorical boosting (CatBoost), adaptive boosting (AdaBoost), light-gradient-boosting machine (LightGBM), random forest (RF), gradient-boosting decision tree (GBDT), decision tree (DT), and ensemble model based on seven algorithms were used to establish the prediction models. A series of indicators such as the area under the ROC curve (AUROC) and the area under the PR curve (AUPR) was used to evaluate the model performance. A total of 94 SAE patients were identified in our samples. Risk factors of SAEs were the number of triggers, length of stay, age, number of combined drugs, ADEs occurred in previous chemotherapy, and sex. In the test cohort, a nomogram based on the logistic model owns the AUROC of 0.799 and owns the AUPR of 0.527. The GBDT has the best predicting abilities (AUROC = 0.832 and AUPR = 0.557) among the eight machine learning models and was better than the nomogram and was chosen to establish the prediction webpage. This study provides a novel method to accurately predict SAE occurrence in cancer inpatients., 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 Zhang, Pan, Chen, Ji, Peng, Tang, Wang, Jia and Gong.)

Objectives: To study the design of nonmetallic crowns for deciduous molars by means of computer aided design and to analyze the key parameters of the nonmetallic crowns of deciduous molars using finite element method. Methods: The three-dimensional model of a mandibular second primary molar was constructed by using a micro-CT system. The thickness of the crown was limited to 0.5 mm and four different crown shapes (chamfer+anatomic, chamfer+non-anatomic, knife edge+anatomic and knife edge+non-anatomic) were designed. Then, the crown shape was limited as chamfer+non-anatomic and five different thicknesses of the crown (0.50, 0.75, 1.00, 1.25, 1.50 mm) were designed, and three different materials, including polyetherketoneketone (PEKK), polymethylmethacrylate (PMMA) resin and resin-infiltrated ceramic, were applied to make the crown. Stress distribution and fatigue of each component of the model under vertical and oblique loadings were analyzed by using finite element method. Non-axial retention analysis was performed on chamfer+non-anatomic crowns, made of PMMA resin, with thicknesses of 0.50, 0.75, 1.00, 1.25 and 1.50 mm. Results: Among the four crown shape designs, the chamfer+non-anatomic type crown showed the lowest von Mises stress and the highest safety factor. By comparing three different materials, the resin-infiltrated ceramic group showed obvious stress concentration on the buccal edge of the crown and the PEKK group showed stress concentration in the adhesive layer. Results of non-axial retention analysis showed that the torques required by the crowns with five thicknesses at the same rotation angle were as follows: 4 856.1, 4 038.1, 3 497.3, 3 256.3 and 3 074.3 N⋅m, respectively. The comparison of areas of the adhesives fracture among groups were as follows: 0.5 mm group < 0.75 mm group < 1.00 mm group < 1.25 mm group < 1.50 mm group. Conclusions: In the design of nonmetallic crowns for primary molars, the edge of the crown should be designed as chamfer, the shape of the inner crown should be non-anatomical and the minimum preparation amount of the occlusal surface should be 1.00 mm. Among the three materials, PMMA resin, of which elastic modulus is similar to the dentin and the dental adhesive, might be the most suitable material for the crowns of primary molars.

Background: Nucleic acids used as drug delivery systems (DDS) have gained attention because of their biosafety and effortless synthesis. G-quadruplex (G4) structured aptamer such as AS1411 was frequently employed to deliver photosensitizers or chemotherapeutic agents while other aptamers were seldomly reported in this field., Methods: Herein, a chemical anticancer drug daunomycin (DNM), and a photosensitizer 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP) were physically assembled with a novel DNA structure composed of an aptamer of vascular endothelial growth factor (VEGF) and a cytosine (C)-rich DNA fragment (gc-34). Spectral and molecular mimicking methods were employed to research the drug loading/releasing process. The in vitro cytotoxicity was studied by MTT, ROS, cell cycle, and cell apoptotic assays and the in vivo anticancer efficiency was evaluated by the inhibitive effect on the cancerous growth of MCF-7 tumor-bearing nude mice., Results: The G4-structured VEGF aptamer delivered TMPyP successfully for the first time. The designed DDS displayed sensitive VEGF/pH controlled drug release. The co-delivery of DNM and TMPyP exhibited high ROS production, significant cell cycle arresting and evident cell apoptosis, and displayed superior cytotoxicity against tumor cells compared with individual agents in vitro. In vivo studies showed that the dual-drug loaded system can greatly inhibit tumor growth with chemotherapeutic/photodynamic synergistic effects., Conclusion: The co-delivery of DNM and TMPyP with aptamer/C-rich DNA successfully integrates the functions of VEGF/pH stimuli-responsive drug release and chemotherapeutic/phototherapeutic modalities into one single system, and may have great potential in cancer treatment., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To record occlusal contact of primary dentition at maximal intercuspal position in children with individual normal occlusion. Methods: A total of 57 children were recruited from patients of the Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology. Inclusion criteria were that the subjects were 3-5 years old with no visually detectable caries or pupal and periapical diseases, had complete primary dentition, had individual normal occlusion, had normal function of craniofacial system, were medically healthy, could cooperate with sampling and had obtained written informed consent from the parents or guardians. Finally, forty-seven children aged 3 to 5 years old were enrolled, including 24 males and 23 females. The age, height and weight of all subjects were (4.1±0.7) years old (ranging 3.0-5.8 years old), (103.7±7.2) cm (ranging 90-120 cm) and (17.1±2.5) kg (ranging 12.5-22.5 kg), respectively. Occlusal abilities such as occlusal contact area, average bite pressure, maximum bite pressure, maximum bite force and occlusal balance were measured with Dental Prescale Ⅱ system. Results: Maximum bite force and occlusal contact area at intercuspal position in children with primary dentition were (567.40±223.84) N (ranging 226.7-1 154.6 N) and (18.56±6.54) mm 2 (ranging 8.4-41.2 mm 2 ), respectively. There was a significantly strong correlation between maximum bite force and occlusal contact area ( r =0.954, P <0.01). Height and weight of children were also positively correlated with their maximum bite force ( r =0.397, P =0.022 and r =0.453, P =0.008, respectively). Maximum occlusal bite force and contact occlusal area of boys [(651.80±224.34) N and (20.77±6.97) mm 2 ] were significantly higher and larger than those of girls [(479.34±190.45) N and (16.25±5.27) mm 2 ] ( P <0.05). Thirty-two of all 47 children had one occlusal contact point with maximum bite pressure, mostly locating within the primary molar region. Bite forces of anterior and posterior teeth of primary dentition were (124.12±56.99) N and (450.11±205.09) N, respectively, about (21.82±11.40)% and (71.80±21.35)% of maximum bite force of the whole primary dentition. All of the occlusal balance points located in posterior teeth regions. Occlusal contacts were observed at both anterior and posterior teeth of primary dentition with individual normal occlusion. Conclusions: There was a great variation of maximum bite forces of primary dentitions at intercuspal position of children with individual normal occlusion. Maximum bite force of primary dentition was significantly correlated with occlusal contact area, height and weight of children. Occlusal contact points with maximum bite pressure and occlusal bite balance points of primary dentitions mostly located in primary molar regions.

Following the publication of our paper (Zhang et al., 2020), it has come to our attention that we erroneously listed two funding sources unrelated to this study in the "ACKNOWLEDGEMENTS" section. Hereby, we wish to update the "ACKNOWLEDGEMENTS" section as a correction.

Atherosclerosis (AS) is characterized by lipids metabolism disorder and inflammatory response. Accumulating evidence has demonstrated that Wingless type 5a (Wnt5a) is implicated in cardiovascular diseases through non-canonical Wnt cascades. However, its precise role during the pathogenesis of AS is still unclear. Therefore, the present study aims to investigate the role and the underlying mechanism of Wnt5a/receptor tyrosine kinase-like orphan receptor 2 (Ror2) pathways in the promotion of AS process through affecting lipid accumulation and inflammation. In atherosclerotic clinical samples, Wnt5a levels were measured by using enzyme-linked immunosorbent assay (ELISA) assay. In vivo experiments were conducted by using apolipoprotein E knockout (apoE - / - ) mice model. Vascular smooth muscle cells (VSMCs) were applied for in vitro studies. Wnt5a was highly expressed in both of atherosclerotic clinical samples and apoE - / - mice. The knockdown of Wnt5a significantly inhibited cholesterol accumulation and inflammatory response. Additionally, the lipopolysaccharide (LPS)-induced inflammation aggravated the cholesterol accumulation and decreased adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression in VSMCs. Depletion of intracellular cholesterol by β-cyclodextrin (β-CD) led to the upregulation of ABCA1 and the inhibition of inflammation. Conversely, the overexpression of Wnt5a inhibited ABCA1 expression, facilitated cholesterol accumulation, impared cholesterol efflux, promoted NF-κB nuclear translocation and the inflammatory cytokines secretion. Moreover, the knockdown of Ror2 increased ABCA1 expression and reduced Wnt5a-induced cholesterol accumulation and inflammatory responses. Furthermore, the knockdown of ABCA1 enhanced cholesterol accumulation and inflammatory response. Therefore, Wnt5a/Ror2 pathway was critical in regulating cholesterol homeostasis and inflammatory response, which might be a promising therapeutic target for AS therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Delivery of exogenous high mobility group box 1 (HMGB1) may exert a beneficial effect on myocardial ischemia-reperfusion (I/R) injury. Since the expression of vascular endothelial growth factor (VEGF) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in the myocardium mediates the cardioprotective function of basic fibroblast growth factor, we hypothesized that VEGF and the PI3K/Akt signaling pathway also mediate the protective effects of intravenously delivered HMGB1. Thus, the objective of the present study was to analyze the impact of intravenous administration of HMGB1 on the myocardial expression of VEGF, myocardial fibrosis, and cardiac function in rats subjected to acute myocardial I/R. The ischemia was induced by ligation of the left anterior descending coronary artery for 30 min and was followed by 3 h of reperfusion. Myocardial malondialdehyde content, infarct size, and collagen volume fraction decreased, while the activity of superoxide dismutase was increased, the expression of VEGF and p-Akt was upregulated, and cardiac function was improved in the HMGB1-treated group when compared with rats subjected to I/R only (all P < 0.05). However, these effects of HMGB1 were abolished by LY294002. The obtained results demonstrate that the cardioprotective effects of intravenous administration of HMGB1 prior to I/R may be mediated by upregulation of myocardial expression of VEGF, which may activate the PI3K/Akt signaling pathway., (Copyright © 2020 Zhou, Han, Gao, Sun, Tang, Wang, Wang and Yao.)

Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys ( Macaca fascicularis ) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.

Background: Neural stem cells (NSCs) transplantation is considered a promising treatment for Parkinson's disease. But most NSCs are differentiated into glial cells rather than neurons, and only a few of them survive after transplantation due to the inflammatory environment., Methods: In this study, neural stem cells (NSCs) and microglial cells both forced with the Nurr1 gene were transplanted into the striatum of the rat model of PD. The results were evaluated through reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunofluorescence analysis., Results: The behavioral abnormalities of PD rats were improved by combined transplantation of NSCs and microglia, both forced with Nurr1. The number of tyrosine hydroxylase+ cells in the striatum of PD rats increased, and the number of Iba1+ cells decreased compared with the other groups. Moreover, the dopamine neurons differentiated from grafted NSCs could still be detected in the striatum of PD rats after 5 months., Conclusions: The results suggested that transplantation of Nurr1-overexpressing NSCs and microglia could improve the inhospitable host brain environments, which will be  a new potential strategy for the cell replacement therapy in PD., (© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Central fatigue is defined as a failure of the central nervous system to adequately drive the muscle, manifesting limited development, and maintenance of locomotor activity. A plateau in hypoxia leads to central fatigue and followed by maximal motility recession. However, the underlying mechanism is still unclear. The present study describes a mechanism by which liver CEBPβ (CCAAT/enhancer-binding protein beta) induced by hypoxic environment alters the kynurenine (KYN) metabolism and causes the suppression of motility function recession. The activation of CEBPβ under hypoxia increases the liver expression of tryptophan dioxygenase, thereby enhancing the conversion of tryptophan into KYN; the KYN metabolite can traverse the blood-brain barrier and result in the suppression of motility function. However, the knockdown of CEBPβ by injecting pAAV-shRNA-CEBPβ via the hepatic portal vein reduces the KYN production and improves the motility function. KYN is a neurochemical that which restricts the exercise capacity after injection in the basal ganglia in mice. Reducing the plasma KYN protects the brain from hypoxia-induced changes associated with fatigue, and the knockdown liver of CEBPβ in mice renders resistance to fatigue post-acute hypoxia or tryptophan treatment. This study reveals resistance to central fatigue as a strategy for acclimatization to hypoxia mediated by transcription factor CEBPβ in the liver.

Autophagy and apoptosis are interlocked in an extensive crosstalk. Our previous study demonstrated that hypotonic hypoxia-induced marked apoptosis of a spermatocyte-derived cell line (GC-2). However, whether hypoxia-induced apoptosis is mediated by inhibition of autophagy under hypoxic conditions remains unclear. In this study, GC-2 cells were cultured in 1% O2 and harvested at different time points. Autophagy was determined by acridine orange staining, cyto-ID staining, mCherry-GFP-LC3B adenovirus transfection and Western blotting for various autophagy markers. Apoptosis was detected by TUNEL staining, flow cytometry, JC-1 staining and Western blotting of apoptosis-related proteins. We found that hypoxia-induced apoptosis of GC-2 cells through mitochondrial and death receptor pathways and inhibited autophagic flux in GC-2 cells in a time-dependent manner. However, while marked autolysosome formation was observed in GC-2 cells before 24-h culture in hypoxic conditions, apparent apoptosis was observed only after 24-h culture in hypoxic conditions. Caspase-8 siRNA treatment induced cell survival, accompanied by induction of the mature autophagosome, acidic vesicular organelle formation and autophagic flux. Furthermore, Beclin-1 overexpression markedly attenuated the impairment of spermatogenesis in mice by inhibiting apoptosis of spermatocytes. The results of this study demonstrate that hypoxia inhibits autophagy, which further enhances hypoxia-induced apoptosis of mouse spermatocytes by promoting caspase-8 activation in a time-dependent manner, suggesting that combined application of apoptosis inhibition and autophagy activation might be a therapeutic strategy for treating hypoxia-induced male infertility.

Introduction: Neural stem cells (NSCs) are the most promising cells for cell replacement therapy for Parkinson's disease (PD). However, a majority of the transplanted NSCs differentiated into glial cells, thereby limiting the clinical application. Previous studies indicated that chronic neuroinflammation plays a vital role in the degeneration of midbrain DA (mDA) neurons, which suggested the developing potential of therapies for PD by targeting the inflammatory processes. Thus, Nurr1 (nuclear receptor-related factor 1), a transcription factor, has been referred to play a pivotal role in both the differentiation of dopaminergic neurons in embryonic stages and the maintenance of the dopaminergic phenotype throughout life., Aim: This study investigated the effect of Nurr1 on neuroinflammation and differentiation of NSCs cocultured with primary microglia in the transwell coculture system., Results: The results showed that Nurr1 exerted anti-inflammatory effects and promoted the differentiation of NSCs into dopaminergic neurons., Conclusions: The results suggested that Nurr1 protects dopaminergic neurons from neuroinflammation insults by limiting the production of neurotoxic mediators by microglia and maintain the survival of transplanted NSCs. These phenomena provided a new theoretical and experimental foundation for the transplantation of Nurr1-overexpressed NSCs as a potential treatment of PD., (© 2018 John Wiley & Sons Ltd.)

Background: Circulating endometrial cells (CECs) have been reported to be present in the peripheral blood of women with endometriosis (EM), providing clear and specific evidence of the presence of ectopic lesions. In this study, we established a method with a high detection rate of CECs, assessed the diagnostic value of CECs for EM and compared with serum CA125, and proposed a hypothesis for the pathogenesis of EM from the new perspective of CECs., Methods: The participants were enrolled prospectively from October 2015 to July 2016. The peripheral blood samples were collected from 59 participants, and the blood cells were isolated for immunofluorescence staining via microfluidic chips. The cells that were positive for vimentin/cytokeratin and estrogen/progesterone receptor and negative for CD45 were identified as CECs. The serum CA125 level was tested with electrochemiluminescence immunoassay., Results: The detection rate of CECs reached 89.5% (17/19) in the EM group, which was significantly higher than that of the control group (15.0% [6/40], P < 0.001) and was independent of menstrual cycle phases. Furthermore, a positive CEC assay detected 4/5 cases of Stage I-II EM. In contrast, a positive CA125 test had limited value in detecting EM (13/19, 68.4%) and detected only one case of Stage I-II EM., Conclusion: CECs are promising biomarkers for EM with great potential for a noninvasive diagnostic assay.

An experiment was conducted to uncover the effects of increasing dietary grain levels on expression of thiamine transporters in ruminal epithelium, and to assess the protective effects of thiamine against high-grain-induced inflammation in dairy cows. Six rumen-fistulated, lactating Holstein dairy cows (627 ± 16.9 kg of body weight, 180 ± 6 d in milk; mean ± standard deviation) were randomly assigned to a replicated 3 × 3 Latin square design trial. Three treatments were control (20% dietary starch, dry matter basis), high-grain diet (HG, 33.2% dietary starch, DM basis), and HG diet supplemented with 180 mg of thiamine/kg of dry matter intake. On d 19 and 20 of each period, milk performance was measured. On d 21, ruminal pH, endotoxic lipopolysaccharide (LPS), and thiamine contents in rumen and blood, and plasma inflammatory cytokines were detected; a rumen papillae biopsy was taken on d 21 to determine the gene and protein expression of toll-like receptor 4 (TLR4) signaling pathways. The HG diet decreased ruminal pH (5.93 vs. 6.49), increased milk yield from 17.9 to 20.2 kg/d, and lowered milk fat and protein from 4.28 to 3.83%, and from 3.38 to 3.11%, respectively. The HG feeding reduced thiamine content in rumen (2.89 vs. 8.97 μg/L) and blood (11.66 vs. 17.63 μg/L), and the relative expression value of thiamine transporter-2 (0.37-fold) and mitochondrial thiamine pyrophosphate transporter (0.33-fold) was downregulated by HG feeding. The HG-fed cows exhibited higher endotoxin LPS in rumen fluid (134,380 vs. 11,815 endotoxin units/mL), and higher plasma concentrations of lipopolysaccharide binding protein and pro-inflammatory cytokines when compared with the control group. The gene and protein expression of tumor necrosis factor α (TNFα), IL1B, and IL6 in rumen epithelium increased when cows were fed the HG diet, indicating that local inflammation occurred. The depressions in ruminal pH, milk fat, and protein of HG-fed cows were reversed by thiamine supplementation. Thiamine supplementation increased thiamine contents in rumen and blood, and also upregulated the relative expression of thiamine transporters compared with the HG group. Thiamine supplementation decreased ruminal LPS (49,361 vs. 134,380 endotoxin units/mL) and attenuated the HG-induced inflammation response as indicated by a reduction in plasma IL6, and decreasing gene and protein expression of pro-inflammatory cytokines in rumen epithelium. Western bottling analysis showed that thiamine suppressed the protein expression of TLR4 and the phosphorylation of nuclear factor kappa B (NFκB) unit p65. In conclusion, HG feeding inhibits thiamine transporter expression in ruminal epithelium. Thiamine could attenuate the epithelial inflammation during high-grain feeding, and the protective effects may be due to its ability to suppress TLR4-mediated NFκB signaling pathways., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Water intake reduction (anti-dipsogenic effects) under hypoxia has been well established, but the underlying reason remains unknown. Our previous report indicated that activated TRPV4 neurons in SFO are associated with anti-dipsogenic effects under hypoxia. Although low partial pressure of blood oxygen directly activates TRPV4, humoral factors could also be involved. In the present study, we hypothesize that adropin, a new endogenous peptide hormone, was rapidly increased (serum and brain) concomitant with reduced water intake in early hypoxia. Also, the nuclear expression of c-Fos, a marker for neuronal activation, related to water-consumption (SFO and MnPO) was inhibited. These effects were mitigated by a scavenger, rat adropin neutralizing antibody, which effectively neutralized adropin under hypoxia. Interestingly, injection of recombinant adropin in the third ventricle of the rats also triggered anti-dipsogenic effects and reduced c-Fos positive cells in SFO, but these effects were absent when TRPV4 was knocked down by shRNA. Moreover, adropin-activated CamKK-AMPK signaling related to TRPV4 calcium channel in SFO in normoxia. These results revealed that dissociative adropin was elevated in acute hypoxia, which was responsible for anti-dipsogenic effects by altering TRPV4-CamKK-AMPK signaling in SFO.

Background: Organizational citizenship behavior (OCB) is important to the development of an organization. Research into factors that foster OCB and the underlying processes are therefore substantially crucial., Objective: The current study aimed to test the association between trait self-control and OCB and the mediating role of consideration for future consequence., Method: Four hundred and ninety-four Chinese employees (275 men, 219 women) took part in the study. Participants completed a battery of self-report measures online that assessed trait self-control, tendencies of consideration of future consequence, and organizational citizenship behavior. Path analysis was conducted and bootstrapping technique (N = 5000), a resampling method that is asymptotically more accurate than the standard intervals using sample variance and assumptions of normality, was used to judge the significance of the mediation., Results: Results of path analysis showed that trait self-control was positively related to OCB. More importantly, the "trait self-control-OCB" link was mediated by consideration of future consequence-future, but not by consideration of future consequence-immediate., Conclusions: Employees with high trait self-control engage in more organizational citizenship behavior and this link can be partly explained by consideration of future consequence-future.

In this paper, a biocompatible and water-soluble fluorescent fullerene (C 60 -TEG-COOH) coated mesoporous silica nanoparticle (MSN) was successfully fabricated for pH-sensitive drug release and fluorescent cell imaging. The MSN was first reacted with 3-aminopropyltriethoxysilane to obtain an amino-modified MSN, and then the water-soluble C 60 with a carboxyl group was used to cover the surface of the MSN through electrostatic interaction with the amino group in PBS solution (pH = 7.4). The release of doxorubicin hydrochloride (DOX) could be triggered under a mild acidic environment (lysosome, pH = 5.0) due to the protonation of C 60 -TEG-COO - , which induced the dissociation of the C 60 -TEG-COOH modified MSN (MSN@C 60 ). Furthermore, the uptake of nanoparticles by cells could be tracked because of the green fluorescent property of the C 60 -modified MSN. In an in vitro study, the prepared materials showed excellent biocompatibility and the DOX-loaded nanocarrier exhibited efficient anticancer ability. This work offered a simple method for designing a simultaneous pH-responsive drug delivery and bioimaging system.

The peripheral neutrophil-monocyte/lymphocyte ratio (NMLR) and intratumoral CD16/CD8 ratio (iMLR) may have prognostic value in hepatocellular carcinoma (HCC) patients after curative resection. In this study, the circulating NMLR was examined 387 HCC patients who underwent curative resection between 2006 and 2009. Intratumoral levels of CD4, CD8, CD16 and CD68 and the CD16/CD8 ratio were determined immunohistologically. The prognostic values of clinicopathological parameters, including NMLR and iMLR, were evaluated. NMLR was predictive of overall survival (OS) and recurrence-free survival (RFS) when patients in the training cohort (n = 256) were separated into high (> 1.2) and low (≤ 1.2) NMLR subgroups. NMLR was also an independent predictor of low alpha-fetoprotein (AFP) expression and early recurrence. High NMLR was associated with increases in clinicopathological variables, including alanine aminotransferase (ALT), tumor number, tumor size and BCLC stage. In addition, iMLR strongly predicted risk of recurrence and patient survival, and was positively correlated with NMLR. These findings were confirmed in an independent validation patient cohort (n = 131). Peripheral NMLR and iMLR may thus be useful prognostic markers, and anti-inflammatory treatment may be beneficial in HCC patients after curative hepatectomy., Competing Interests: No potential conflicts of interest.

Thyrotoxic periodic paralysis (TPP) frequently occurs on male individuals at their third and forth decades. The major site of involvement is the proximal muscles of lower limbs. Increasing evidence has shown that the occurrence of TPP is determined by multiple factors. We hypothesized that apart from hormonal fluctuations, skeletal muscle itself may explain for the age and sex variance as well. Our study was established to explore whether the size of lower limb skeletal muscles were related to TPP. We conducted a clinical experiment including 43 patients diagnosed with TPP (Group 1) and 39 pure hyperthyroidism individuals (Group 2). Current age, body mass index (BMI), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), average girth of bilateral upper arm and thigh, physical activity level (PAL) were measured. We also adopted B mode ultrasound to quantify the muscle thickness (MT) of the major muscle involved in the disease, the quadriceps femoris (QF, including rectus femoris, RF; vastus intermedius, VI; vastus medialis, VM and vastus lateralis, VL). Patients were matched in TSH, FT4 and FT3. PAL was also statistically identical between groups. Age, BMI, thigh girth, the average of bilateral MT of QF were statistically different. After adjusting for age, BMI and girth, Group 1 still presented with larger MT of QF than Group 2, regardless of their current thyroid hormone level. There indeed exists an independent relationship between muscle thickness and TPP., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Six new (A5-A6, A8-A11) and six known (A1-A4, A7, PO) α-pyrone compounds were synthesized with dehydroacetate and aldehydes in tetrahydrofuran at room temperature. And their structures were determined by (1)H-NMR, (13)C-NMR and mass spectroscopy. In the bioscreening experiments, ten compounds (A1-A5, PO, A7-A10) exhibited antibacterial activities against Staphylococcus aureus ATCC 25923 with minimum inhibitory concentration (MIC) values of 4-512 mg/L, and nine compounds (A1-A5, PO, A7-A8, A10) exhibited antibacterial activities against Methicillin-resistant S. aureus (MRSA) ATCC 43300 with MIC values of 4-256 mg/L. Moreover, compound A10 showed the highest antibacterial activity against S. aureus ATCC 25923 and MRSA with MIC values of 4 mg/L, while the MIC values of Amoxicillin were 8 mg/L and >256 mg/L, respectively. Two compounds (A8 and PO) exhibited antibacterial activities against Escherichia coli ATCC 25922 with MIC values of 32-512 mg/L. However, only one compound (A8) exhibited significant antibacterial activity against Pseudomonas aeruginosa CVCC 3360 with MIC value of 256 mg/L. Moreover, A10 exhibited significant inhibition of proliferation in the four cell lines MCF-10, A549, A2780 and MFC, and showed stronger inhibitive activity of these four selected cell lines than cisplatin in the cytotoxic assay. Thus, this study suggests that pogostone analogues, especially A10, represented a kind of promising antibacterial and antineoplastic agents., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Preoperative neutrophil-to-lymphocyte ratio (NLR) has been identified as a predictor for the recurrence of hepatocellular carcinoma (HCC), but the cut-off of NLR is inconsistent in various studies. Thus, we detected the prognostic value of preoperative NLR in the single-nodule small HCC (SHCC) patients using X-tile for cutpoint., Methods: Between January 2007 and December 2010, a total of 222 single-nodule SHCC patients underwent curative resection and were examined for the prognostic roles of preoperative NLR by X-tile., Results: In this study, all patients were divided into the low-NLR subgroup (NLR ≤ 2.1) and the high-NLR subgroup (NLR > 2.1) by X-tile. Preoperative NLR showed predictive value for time to recurrence (TTR) and overall survival (OS). Moreover, NLR was associated with total bilirubin, white blood cell counts, and HBsAg, respectively (P = 0.012, <0.001, and 0.011, respectively). Especially, NLR could discriminate the outcome of patients in the subgroup with alpha-fetoprotein (AFP) levels of ≤400 ng/mL. Importantly, postoperative transcatheter arterial chemoembolization (TACE) had close relationship with OS (P = 0.001) and TTR (P ≤ 0.001)., Conclusions: Therefore, this study indicates that preoperative NLR, divided by X-tile for the cutpoint, is a simple prognostic marker for the patients with single-nodule SHCC after curative resection.

This work presented a highly efficient antibacterial Ti-surface which was grafted with poly(N-hydroxyethylacrylamide) (PHEAA) brush and further decorated with triclosan (TCS). The modified surfaces were characterized using contact angle measurements, X-ray photoelectron spectroscopy, and attenuated total reflectance Fourier transform infrared. The antibacterial performance of the modified surfaces was evaluated using the Streptococcus mutans and Actinomyces naeslundii attachment test. The Ti surface with PHEAA brush (Ti-PHEAA) was able to resist the adhesion of the bacteria, while the TCS-decorated Ti surface (Ti-TCS) showed the capability of killing the bacteria adhered on the surface. As we coupled the TCS to the PHEAA brush, the surface showed highly efficient antibacterial performance due to the combination of the resistance to the bacteria adhesion and its activity of killing bacteria.

In this paper, a glucose and pH-responsive release system based on polymeric network capped mesoporous silica nanoparticles (MSN) has been presented. The poly(acrylic acid) (PAA) brush on MSN was obtained through the surface-initiated atom transfer radical polymerization (SI-ATRP) of t-butyl acrylate and the subsequent hydrolysis of the ester bond. Then the PAA was glycosylated with glucosamine to obtain P(AA-AGA). To block the pore of silica, the P(AA-AGA) chains were cross-linked through the formation of boronate esters between 4,4-(ethylenedicarbamoyl)phenylboronic acid (EPBA) and the hydroxyl groups of P(AA-AGA). The boronate esters disassociated in the presence of glucose or in acidic conditions, which lead to opening of the mesoporous channels and the release of loaded guest molecules. The rate of release could be tuned by varying the pH or the concentration of glucose in the environment. The combination of two stimuli exhibited an obvious enhanced release capacity in mild acidic conditions (pH 6.0).

Objective: To analyze the results of malaria surveillance in Huai' an District in the recent 5 years, so as to provide the evidences for the establishment of suitable control strategy in the district., Methods: The febrile patients among permanent and floating populations in Huai'an District from 2009 to 2013 were examined by immunity and etiology methods and the mosquito vector in this district were investigated. Results In recent 5 years, a total of 48,203 person-times among permanent population were examined, and no positives ones were found, and totally 360 person-times among floating population were examined, and 53 cases of malaria were detected, including 2 vivax malaria cases, 48 falciparum malaria cases and 2 undifferentiated cases, and the positive rate of the floating population was 14.72%. All the cases were exported workers infected in Africa and Southeast Asia. A total of 1,048 Anopheles sinensis mosquitoes were captured in 2003, no other Anopheles mosquitoes were found., Conclusions: In recent 5 years, no local malaria cases have been found in Huai' an District, but the imported cases increase, and moreover, the mosquito vector and the transmission condition of malaria still exist.

A novel multicatalytic MBH-Michael tandem reaction has been developed for the asymmetric assembly of ninhydrin, nitroolefins and aldehydes into a structurally complex oxa-spirocyclic indanone backbone. Successive iodocyclization allowed us to convert these multifunctional allylic products into fused chiral natural product mimics.

Background: Treatment for forearm deformities caused by hereditary multiple osteochondromas is still controversial. The purpose of the study was to describe the outcome of treatment with the combined use of ulnar lengthening and excision of osteochondromas., Methods: Fourteen patients with hereditary multiple osteochondromas had forearm deformities which belongs to type I Masada deformity. The mean relative ulnar shortening was 19.9 mm (range, 16-23). All patients ranging from 4 to 15 years old had operative treatment. Clinical evaluation involving the assessment of pain, activities of daily living, and range of motion of the wrist and forearm was performed. The radiographic evaluation was relative ulnar shortening (RUS), radial articular angle (RAA), carpal slip (CS), and radial bowing. Besides, we also evaluated the amount of ulnar lengthening, external fixation time, and external fixation index., Results: The mean EFT was 101 days (range, 84-133), and the mean external fixation index was 44.4 days/cm (range, 33.6-51.2). During the mean 43.1 months follow-up, four patients had mild pain and two patients had mild restriction of daily activities. The rotation of forearm and motion of wrist had increased except in Case 3. The RAA, CS, and radial bowing had been improved except in Case 6 and 7. In all patients, relative ulnar shortening had been corrected. According to the functional evaluation criteria recommended by Krimmer, there were ten excellent and four good., Conclusions: The combined use of ulna lengthening and excision of osteochondromas is a proper and effective treatment method to the type I Masada deformity with the relative ulnar shortening more than 15 mm.