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Xiao-Yan Chen,1,2 Qing-Mei Yang,1,2 Jian-Xiu Fang,1,2 Hai-Feng Guo1,2 1Department of Ultrasound, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, People’s Republic of China; 2Department of Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Xiao-Yan ChenDepartment of Ultrasound, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, No. 99 Longcheng Street, Taiyuan, 030032, People’s Republic of ChinaTel +8613934200119Email che_xiaoyan2@126.comBackground: Patients with hypertension complicated by acute myocardial infarction (AMI) have a generally poor prognosis. The identification of powerful predictors for recurring cardiovascular events (RCEs) is vital. This study seeks to evaluate the predictive value of three-dimensional (3D) strain parameters for RCEs in patients with hypertension complicated by AMI.Methods: We successfully followed up patients with hypertension and AMI from April 2015 to December 2015 in this retrospective study. Participants previously underwent 3D echocardiography, one week, and one month after percutaneous coronary intervention (PCI). The left ventricular structural function parameters, as well as 3D strain parameters including 3D global longitudinal strain (3D-GLS), 3D global circumferential strain, 3D global radial strain, and 3D global area strain (3D-GAS), were acquired. A Cox model was used to determine the relationships between these parameters and RCEs.Results: In total, 62 patients were enrolled in the analysis. During follow-up (41.27 ± 20.45 months), 20 patients (32.3%) had RCEs that were independently predicted one month after PCI by 3D-GLS (HR: 1.481, 95% CI: 1.202– 1.824, P < 0.001) and 3D-GAS (HR: 1.254, 95% CI: 1.093– 1.440, P = 0.001). The optimal cutoffs for 3D-GLS and 3D-GAS in predicting cardiac events were ≥ 12.5% (area under the receiver operating characteristic curve [AUC]: 0.736, 95% CI: 0.611– 0.862, P = 0.003), and > 20.5% (AUC: 0.685, 95% CI: 0.551– 0.818, P = 0.020), respectively.Conclusion: The assessed values of 3D-GLS and 3D-GAS one month after PCI can predict RCEs in patients with hypertension complicated by AMI.Keywords: hypertension, acute myocardial infarction, three-dimensional speckle tracking echocardiography, strain, cardiovascular events

David R Powell,1 Jean-Pierre Revelli,1 Deon D Doree,1 Christopher M DaCosta,1 Urvi Desai,1 Melanie K Shadoan,1 Lawrence Rodriguez,2 Michael Mullens,2 Qi M Yang,1 Zhi-Ming Ding,1 Laura L Kirkpatrick,3 Peter Vogel,1 Brian Zambrowicz,1– 3 Arthur T Sands,1– 3 Kenneth A Platt,3 Gwenn M Hansen,3 Robert Brommage1 1Department of Pharmaceutical Biology, Lexicon Pharmaceuticals, Inc, The Woodlands, TX, USA; 2Department of Information Technology, Lexicon Pharmaceuticals, Inc, The Woodlands, Tx, USA; 3Department of Molecular Biology, Lexicon Pharmaceuticals, Inc, The Woodlands, Tx, USACorrespondence: David R PowellDepartment of Pharmaceutical Biology, Lexicon Pharmaceuticals, Inc, 2445 Technology Forest Boulevard, The Woodlands, Tx, 77381, USATel +1 713 249 3972Fax +1 281 863 8115Email dpowell@lexpharma.comPurpose: Obesity is a major public health problem. Understanding which genes contribute to obesity may better predict individual risk and allow development of new therapies. Because obesity of a mouse gene knockout (KO) line predicts an association of the orthologous human gene with obesity, we reviewed data from the Lexicon Genome5000TM high throughput phenotypic screen (HTS) of mouse gene KOs to identify KO lines with high body fat.Materials and Methods: KO lines were generated using homologous recombination or gene trapping technologies. HTS body composition analyses were performed on adult wild-type and homozygous KO littermate mice from 3758 druggable mouse genes having a human ortholog. Body composition was measured by either DXA or QMR on chow-fed cohorts from all 3758 KO lines and was measured by QMR on independent high fat diet-fed cohorts from 2488 of these KO lines. Where possible, comparisons were made to HTS data from the International Mouse Phenotyping Consortium (IMPC).Results: Body fat data are presented for 75 KO lines. Of 46 KO lines where independent external published and/or IMPC KO lines are reported as obese, 43 had increased body fat. For the remaining 29 novel high body fat KO lines, Ksr2 and G2e3 are supported by data from additional independent KO cohorts, 6 (Asnsd1, Srpk2, Dpp8, Cxxc4, Tenm3 and Kiss1) are supported by data from additional internal cohorts, and the remaining 21 including Tle4, Ak5, Ntm, Tusc3, Ankk1, Mfap3l, Prok2 and Prokr2 were studied with HTS cohorts only.Conclusion: These data support the finding of high body fat in 43 independent external published and/or IMPC KO lines. A novel obese phenotype was identified in 29 additional KO lines, with 27 still lacking the external confirmation now provided for Ksr2 and G2e3 KO mice. Undoubtedly, many mammalian obesity genes remain to be identified and characterized.Keywords: obesity, druggable, homologous recombination, gene trapping

Jian-Xiu Fang, Xiao-Yan Chen, Qing-Mei Yang, Meng-Hua Xue Department of Ultrasound, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, 030032, People’s Republic of ChinaCorrespondence: Jian-Xiu FangDepartment of Ultrasound, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, No. 99 Longcheng Street, Xiaodian District, Taiyuan, Shanxi Province, 030032, People’s Republic of ChinaTel/ Fax +86 139 34534690Email fangjx_sd@163.comObjective: Glomerulosclerosis and tubulointerstitial fibrosis are associated with lower renal parenchymal resilience. The purpose of this study is to determine the factors influencing renal resilience in patients with diabetic nephropathy (DN).Methods: We recruited 56 healthy volunteers and 187 patients with DN. All the participants were evaluated using shear-wave elastography (SWE), and the size of their kidneys and Young’s modulus values for the parenchyma were recorded. A total of 187 patients with DN are allocated to three groups according to their urinary albumin-to-creatinine ratio: normoalbuminuric (< 30 mg/g creatinine), microalbuminuric (30– 300 mg/g), and macroalbuminuric (≥ 300 mg/g) groups. Renal resilience is compared between the stages of diabetic nephropathy and the healthy control group, and the factors affecting the stiffiness of the renal parenchyma in DN are analyzed.Results: The renal parenchyma is harder in participants with DN than in healthy participants (P < 0.001), and the stiffiness increases with the progression of the disease (P < 0.001). Multivariate logistic regression analysis shows that disease stage (β = 0.789, P < 0.001), duration of diabetes (β = 0.028, P < 0.001), and serum creatinine (SCr) concentration (β = 0.001, p < 0.001) influence the stiffiness of the renal parenchyma.Conclusion: We show that SWE can be used to measure changes in the stiffiness of the renal parenchyma in patients with DN. Furthermore, Young’s modulus of the renal parenchyma is related to the duration of diabetes, urinary albumin excretion, and SCr concentration. Thus, SWE can be used to objectively and non-invasively stage DN.Keywords: diabetic nephropathy, shear-wave elastography, Young’s modulus, parenchymal stiffiness

This study aimed to assess the burden and influencing factors among primary caregivers of children with congenital microtia. A total of 153 primary caregivers of children with congenital microtia who underwent auricular reconstruction surgery at a tertiary A-grade hospital in Xi'an between October 2019 and August 2022, were recruited using convenience sampling. The Zarit Caregiver Burden Interview (ZBI) was employed to evaluate caregiver burden. While convenience sampling allowed for the practical recruitment of participants, its limitations include potential selection bias, which may affect the generalizability of the results. The mean total ZBI score was 30.07 ± 12.29. Among the participants, 26 caregivers (17.0%) reported no burden, 102 caregivers (66.7%) reported mild burden, 22 caregivers (14.4%) reported moderate burden, and 3 caregivers (2.0%) reported severe burden. Multivariate regression analysis identified several significant factors influencing caregiver burden, including the location and severity of the lesion, educational level, method of medical payment, monthly household income, communication with others about the child's condition, caregiver self-blame or guilt, and family support (all P < .05). Primary caregivers of children with congenital microtia face substantial burdens, emphasizing the need for targeted healthcare interventions. Strategic approaches are essential to address the psychological, social, and financial challenges they encounter. Future research should focus on longitudinal studies and interventions to enhance caregiver well-being and patient outcomes. However, caution is advised when generalizing these findings due to the sampling limitations., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To investigate the feasibility and clinical effect of the treatment of NeerⅡb distal clavicular fracture with locking plate under arthroscopy., Methods: Between June 2018 and September 2022, the medical records of 15 patients with NeerⅡb distal clavicular fracture treated with locking plate under arthroscope were retrospectively analyzed, including 9 males and 6 females, aged from 25 to 57 years old with an average of (42.50±7.75) years old, 5 left shoulder, 10 right shoulder, and duration of the disease ranged from 4 to 7 days with an average of (5.16±0.98) d. Visual analog score (VAS), Constant-Murley shoulder joint score scale and Neer standard score were used before operation, 1 month after operation and the last follow-up., Results: All patients successfully completed the treatment of NeerⅡb distal clavicular fracture with locking plate under arthroscopy, with the operation time ranging from 0.3 to1.0 h with an average of (0.55±0.24) h. All patients were healed at stageⅠ. The follow-up time ranged from 6 to 15 months with an average of (9.2±2.8) months. The preoperative VAS score was 7.23±0.67, the Constant-Murley shoulder joint score was (19.57±0.91), and the Neer standard score was (11.27±1.12);The VAS score was (1.56±0.81), the Constant-Murley shoulder joint score was (52.62±1.54), and the Neer standard score was (61.98±2.99) in the first month after operation;At the last follow-up, the VAS was (0.42±0.54), the Constant-Murley shoulder joint score was (91.24±1.97), and the Neer standard score was (93.24±3.38). The difference between VAS, Constant-Murley shoulder joint score and Neer standard score was statistically significant at one month postoperative and preoperative ( P <0.05), and the difference between the last follow-up visit and one month postoperative was statistically significant ( P <0.05)., Conclusion: The treatment of NeerⅡb distal clavicular fracture with locking plate under arthroscope can restore the function of shoulder joint, with definite curative effect and feasibility.

Mussel byssal proteins are of biomimetic importance for the development of novel underwater bio-adhesive agents. It is important to maintain a reduced state during the process of byssus adhesion. There are 19 mussel foot proteins (MFPs) have been reported in previous studies, among which only MFP-6 had been confirmed as an antioxidant protein in mussel byssus due to the function of cysteines, and playing an essential role in the redox balance of mussel byssus during adhesion process. Although the other four MFPs (MFP-16 ~ MFP-19) also have abundant cysteines, their function is still unknown. In this study, a novel mussel foot protein, named MFP-20, was identified from Mytilus coruscus foot. The sequential features, expression profile, and function of recombinant MFP-20 were verified. The results showed that MFP-20 has more abundant cysteines than other MFPs, the relative expression of mfp-20 was upregulated in Fe 3+ stress and low pH seawater. In addition, different adhesive substrates induced significant changes of expression level of mfp-20. Furthermore, rMFP-20 showed strong antioxidant capacity in the DPPH assay, and the abundant cysteines in its sequence may play vital roles in the antioxidation activity. Our findings revealed the possible function of MFP-20 with a totally different sequence from the reported MFP-6 and provided new clues for exploring the redox balance of mussel byssus during the adhesion process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Cardiac fibrosis is a pathological scarring process that impairs cardiac function. N-acetyltransferase 10 (Nat10) is recently identified as the key enzyme for the N4-acetylcytidine (ac4C) modification of mRNAs. In this study, we investigated the role of Nat10 in cardiac fibrosis following myocardial infarction (MI) and the related mechanisms. MI was induced in mice by ligation of the left anterior descending coronary artery; cardiac function was assessed with echocardiography. We showed that both the mRNA and protein expression levels of Nat10 were significantly increased in the infarct zone and border zone 4 weeks post-MI, and the expression of Nat10 in cardiac fibroblasts was significantly higher compared with that in cardiomyocytes after MI. Fibroblast-specific overexpression of Nat10 promoted collagen deposition and induced cardiac systolic dysfunction post-MI in mice. Conversely, fibroblast-specific knockout of Nat10 markedly relieved cardiac function impairment and extracellular matrix remodeling following MI. We then conducted ac4C-RNA binding protein immunoprecipitation-sequencing (RIP-seq) in cardiac fibroblasts transfected with Nat10 siRNA, and revealed that angiomotin-like 1 (Amotl1), an upstream regulator of the Hippo signaling pathway, was the target gene of Nat10. We demonstrated that Nat10-mediated ac4C modification of Amotl1 increased its mRNA stability and translation in neonatal cardiac fibroblasts, thereby increasing the interaction of Amotl1 with yes-associated protein 1 (Yap) and facilitating Yap translocation into the nucleus. Intriguingly, silencing of Amotl1 or Yap, as well as treatment with verteporfin, a selective and potent Yap inhibitor, attenuated the Nat10 overexpression-induced proliferation of cardiac fibroblasts and prevented their differentiation into myofibroblasts in vitro. In conclusion, this study highlights Nat10 as a crucial regulator of myocardial fibrosis following MI injury through ac4C modification of upstream activators within the Hippo/Yap signaling pathway., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Prunin of desirable bioactivity and bioavailability can be transformed from plant-derived naringin by the key enzyme α-L-rhamnosidase. However, the production was limited by unsatisfactory properties of α-L-rhamnosidase such as thermostability and organic solvent tolerance. In this study, biochemical characteristics, and hydrolysis capacity of a novel α-L-rhamnosidase from Spirochaeta thermophila (St-Rha) were investigated, which was the first characterized α-L-rhamnosidase for Spirochaeta genus. St-Rha showed a higher substrate specificity towards naringin and exhibited excellent thermostability and methanol tolerance. The K m of St-Rha in the methanol cosolvent system was decreased 7.2-fold comparing that in the aqueous phase system, while k cat /K m value of St-Rha was enhanced 9.3-fold. Meanwhile, a preliminary conformational study was implemented through comparative molecular dynamics simulation analysis to explore the mechanism underlying the methanol tolerance of St-Rha for the first time. Furthermore, the catalytic ability of St-Rha for prunin preparation in the 20% methanol cosolvent system was explored, and 200 g/L naringin was transformed into 125.5 g/L prunin for 24 h reaction with a corresponding space-time yield of 5.2 g/L/h. These results indicated that St-Rha was a novel α-L-rhamnosidase suitable for hydrolyzing naringin in the methanol cosolvent system and provided a better alternative for improving the efficient production yield of prunin., Competing Interests: Declaration of Competing Interest We confirm that there are no any conflicts of interest with respect to this publication and there has been no financial support for this article that could influence the outcome., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: One-fourth of Parkinson's disease (PD) patients suffer from cognitive impairment. However, few neuroimaging markers have been identified regarding cognitive impairment in PD., Objective: This study aimed to explore the association between third ventricular width by transcranial sonography (TCS) and cognitive decline in PD., Method: Participants with PD were recruited from one medical center in China. Third ventricular width was assessed by TCS, and cognitive function was analyzed by the Mini-Mental State Examination (MMSE). Receiver operating characteristic (ROC) analysis and Cox model analysis were utilized to determine the diagnostic and predictive accuracy of third ventricular width by TCS for cognitive decline in PD patients., Result: A total of 174 PD patients were recruited. Third ventricular width was negatively correlated with MMSE scores. ROC analysis suggested that the optimal cutoff point for third ventricular width in screening for cognitive impairment in PD was 4.75 mm (sensitivity 62.7%; specificity 75.6%). After 21.5 (18.0, 26.0) months of follow-up in PD patients without cognitive impairment, it was found that those with a third ventricular width greater than 4.75 mm exhibited a 7.975 times higher risk of developing cognitive impairment [hazard ratio = 7.975, 95% CI 1.609, 39.532, p = 0.011] compared with patients with a third ventricular width less than 4.75 mm., Conclusion: Third ventricular width based on TCS emerged as an independent predictor of developing cognitive impairment in PD patients., (© 2023 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Aim: Aim The objective of this study was to understand the occupational protective behaviors of newly recruited nurses and explore the influencing factors., Methods: A convenience sampling method was used to select newly recruited nurses in our hospital from July 2018 to November 2019. The survey was conducted using the general information questionnaire, work attitude scale (Wa), and occupational protective behavior scale., Results: The total score of occupational protective behaviors of 150 newly enrolled nurses was 18.94 ± 3.59. There was a significant negative correlation between work attitude score and occupational protective behaviors (r = -0.324, p < 0.001). Multiple linear regression analysis showed that gender, previous participation in nursing skill-based competitions, experience of needlestick injuries before recruit, work attitude score, average daily sleep time (p < 0.05) were independent factors influencing occupational protective behaviors., Conclusions: The overall occupational protective awareness of newly enrolled nurses is relatively weak and needs to be further improved. The group's ability to improve occupational protective behaviors may be positively impacted through increased adaptability, improved sleep, active participation in nursing skill-based competitions, strengthening guidance and education on occupational protection., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The low maturation rate of oocytes is an important reason for female infertility and failure of assisted pregnancy. The germinal vesicle breakdown (GVBD) is a landmark event of oocyte maturation. In our previous studies, we found that zona pellucida 3 (ZP3) was strongly concentrated in the nuclear region of germinal vesicle (GV) oocytes and interacted with aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) and lamin A to promote GVBD. In the current study, we found that lamin A is mainly concentrated in the nuclear membrane. When ZP3 is knocked down, lamin A will be partially transferred to the nucleus of oocytes. The prelamin A is increased in both the nuclear membrane and nucleus, while phosphorylated lamin A (p-lamin A) is significantly reduced. AIPL1 was also proved to accumulate in the GV region of oocytes, and ZP3 deletion can significantly inhibit the aggregation of AIPL1 in the nuclear region. Similar to ZP3 knockdown, the absence of AIPL1 resulted in a decrease in the occurrence of GVBD, an increase in the amount of prelamin A, and a significant decrease in p-lamin A in oocytes developed in vitro . Finally, we propose the hypothesis that ZP3 can stabilize farnesylated prelamin A on the nuclear membrane of AIPL1, and promote its further processing into mature lamin A, therefore promoting the occurrence of GVBD. This study may be an important supplement for the mechanism of oocyte meiotic resumption and provide new diagnostic targets and treatment clues for infertility patients with oocyte maturation disorder.

Baicalin (BG) is a bioactive flavonoid extracted from the dried root of the medicinal plant, Scutellaria radix (SR) (dicotyledonous family, Labiatae), and has several biological activities. Polyethylene glycol 400 (PEG400) has been used as a suitable solvent for several traditional Chinese medicines (TCM) and is often used as an excipient for the compound preparation of SR. However, the drug-excipient interactions between BG and PEG400 are still unknown. Herein, we evaluated the effect of a single intravenous PEG400 administration on the BG levels of rats using pharmacokinetic and tissue distribution studies. A liver microsome and recombinant enzyme incubation system were used to further confirm the interaction mechanism between PEG400 and UDP-glucuronosyltransferases (UGTs) (UGT1A8 and UGT1A9). The pharmacokinetic study demonstrated that following the co-intravenous administration of PEG400 and BG, the total clearance (CL z ) of BG in the rat plasma decreased by 101.60% (p < 0.05), whereas the area under the plasma concentration-time curve (AUC) 0-t and AUC 0-inf increased by 144.59% (p < 0.05) and 140.05% (p < 0.05), respectively. Additionally, the tissue distribution study showed that the concentration of BG and baicalein-6-O-β-D-glucuronide (B6G) in the tissues increased, whereas baicalein (B) in the tissues decreased, and the total amount of BG and its metabolites in tissues altered following the intravenous administration of PEG400. We further found that PEG400 induced the UGT1A8 and UGT1A9 enzyme activities by affecting the maximum enzymatic velocity (V max ) and Michaelis-Menten constant (K m ) values of UGT1A8 and UGT1A9. In conclusion, our results demonstrated that PEG400 interaction with UGTs altered the pharmacokinetic behaviors and tissue distribution characteristics of BG and its metabolites in rats., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflict of interests., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

κ-carrageenases are members of the glycoside hydrolase family 16 (GH16) that hydrolyze sulfated galactans in red algae, known as κ-carrageenans. In this study, a novel κ-carrageenase gene from the marine bacterium Rhodopirellula sallentina SM41 (RsCgk) was discovered via the genome mining approach. There are currently no reports on κ-carrageenase from the Rhodopirellula genus, and RsCgk shares a low identity (less than 65%) with κ- carrageenase from other genera. The RsCgk was heterologously overexpressed in Escherichia coli BL21 and characterized for its enzymatic properties. RsCgk exhibited maximum activity at pH 7.0 and 40 °C, and 50% of its initial activity was retained after incubating at 30 °C for 2 h. More than 70% of its activity was maintained after incubation at pH 6.0-8.0 and 4 °C for 24 h. As a marine derived enzyme, RsCgk showed excellent salt tolerance, retaining full activity in 1.2 M NaCl, and the addition of NaCl greatly enhanced its thermal stability. Mass spectrometry analysis of the RsCgk hydrolysis products revealed that the enzyme had high degradation specificity and mainly produced κ-carrageenan disaccharide. Comparative molecular dynamics simulations revealed that the conformational changes of tunnel-forming loops under salt environments may cause the deactivation or stabilization of RsCgk. Our results demonstrated that RsCgk could be utilized as a potential tool enzyme for efficient production of κ-carrageenan oligosaccharides under high salt conditions., Competing Interests: The authors declare no competing financial interest.

Objective: To evaluate clnical effect of minimally invasive osteotomy with absorbable screws in treating hallux valgus deformity., Methods: Clnical data of 31 patients with hallux valgus deformity were retrospective analyzed from January 2019 to December 2020, and divided into absorbable screws group (17 patients) and titanium cannulated screw group (14 patients). In absorbable screws group, there were 1 male and 16 females aged from 32 to 72 years old with an average of (54.53±12.12) years old;6 patients on the left side, 5 on bilateral and 6 on the right side;1 patient was mild, 11 moderate and 5 severe;treated with minimally invasive osteotomy and fixation of absorbable screws. In titanium cannulated screw group, there were 2 males and 12 females aged from 18 to 71 years old with an average of (47.57±15.68) years old;4 patients on the left side, 4 on bilateral and 6 on the right side;1 patient was mild, 9 moderate and 4severe;treated with minimally invasive osteotomy and fixation of titanium cannulated screw. Complications between two groups were observed, changes of hallux valgus angle (HVA)and intermetatarsal angle (IMA)were detected and compared before and after operation at 12 months, American Orthopedic Foot and Ankle Society(AOFAS) and visual analogue scale(VAS) before and after operation at 12 months were also compared., Results: All 31 patients were followed up from 13 to 20 months with an average of (16.61±2.47) months. Patients in absorbable screws group were followed up from 14 to 20 months with an average of (16.88±2.80) months, while patients in titanium cannulated screw group were followed up from 13 to 19 months with an average of (16.29±2.05) months;there was no difference between two groups( P >0.05). One patient in absorbable screws group occurred numbness around incision, 3 patients in titanium cannulated screw group occurred complications, including numbness around incision in 1 patient, skin irritation due to internal fixation in 1 patient, and recurrence in 1 case;there was no statistic difference between two groups ( χ 2 =1.651, P =0.199). There were no statistic difference in HVA and IMA between two groups before and after operation at 12 months( P >0.05). There were no statistic difference between two groups in AOFAS and VAS before and after operation at 12 months( P >0.05)., Conclusion: Compare with mainstream fixation with titanium hollow screw after minmally invasive osteotomy, fixation with absorbable screw could achieve comparable clinical outcome on the basis of images and function evaluation.

Climate change, especially weather extremes like extreme cold or extreme hot, is a major challenge for global livestock. One of the animal breeding goals for sustainable livestock production should be to breed animals with excellent climate adaptability. Indigenous livestock and poultry are well adapted to the local climate, and they are good resources to study the genetic footprints and mechanism of the resilience to weather extremes. In order to identify selection signatures and genes that might be involved in hot adaptation in indigenous chickens from different tropical climates, we conducted a genomic analysis of 65 indigenous chickens that inhabit different climates. Several important unique positively selected genes (PSGs) were identified for each local chicken group by the cross-population extended haplotype homozygosity (XP-EHH). These PSGs, verified by composite likelihood ratio, genetic differentiation index, nucleotide diversity, Tajima's D, and decorrelated composite of multiple signals, are related to nerve regulation, vascular function, immune function, lipid metabolism, kidney development, and function, which are involved in thermoregulation and hot adaptation. However, one common PSG was detected for all three tropical groups of chickens via XP-EHH but was not confirmed by other five types of selective sweep analyses. These results suggest that the hot adaptability of indigenous chickens from different tropical climate regions has evolved in parallel by taking different pathways with different sets of genes. The results from our study have provided reasonable explanations and insights for the rapid adaptation of chickens to diverse tropical climates and provide practical values for poultry breeding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2022 Xu, Liu, Yang, Bian, Li and Zhao.)

The dynamic recrystallization (DRX) features and the evolution of the microstructure of a new hot isostatic pressed (HIPed) powder metallurgy (P/M) superalloy are investigated by hot-compression tests. The sensitivity of grain dimension and DRX behavior to deformation parameters is analyzed. The results reveal that the DRX features and grain-growth behavior are significantly affected by deformation conditions. The DRX process is promoted with a raised temperature/true strain or a reduced strain rate. However, the grains grow up rapidly at relatively high temperatures. At strain rates of o.1 s -1 and 1 s -1 , a uniform microstructure and small grains are obtained. Due to the obvious differences in the DRX rate at various temperatures, the piecewise DRX kinetics equations are proposed to predict the DRX behavior. At the same time, a mathematical model for predicting the grain dimension and the grain growth behavior is established. To further analyze the DRX behavior and the changes in grain dimension, the hot deformation process is simulated. The developed grain-growth equation as well as the piecewise DRX kinetics equations are integrated into DEFORM software. The simulated DRX features are consistent with the test results, indicating that the proposed DRX kinetics equations and the established grain-growth model can be well used for describing the microstructure evolution. So, they are very useful for the practical hot forming of P/M superalloy parts.

As an important enzyme involved in the marine carbon cycle, alginate lyase has received extensive attention because of its excellent degradation ability on brown algae, which is widely utilized for alginate oligosaccharide preparation or bioethanol production. In comparison with endo-type alginate lyases (PL-5, PL-7, and PL-18 families), limited studies have focused on PL-17 family alginate lyases, especially for those with special characteristics. In this study, a novel PL-17 family alginate lyase, Aly23, was identified and cloned from the marine bacterium Pseudoalteromonas carrageenovora ASY5. Aly23 exhibited maximum activity at 35 °C and retained 48.93% of its highest activity at 4 °C, representing an excellent cold-adaptation property. Comparative molecular dynamics analysis was implemented to explore the structural basis for the cold-adaptation property of Aly23. Aly23 had a high substrate preference for poly β-D-mannuronate and exhibited both endolytic and exolytic activities; its hydrolysis reaction mainly produced monosaccharides, disaccharides, and trisaccharides. Furthermore, the enzymatic hydrolyzed oligosaccharides displayed good antioxidant activities to reduce ferric and scavenge radicals, such as hydroxyl, ABTS + , and DPPH. Our work demonstrated that Aly23 is a promising cold-adapted biocatalyst for the preparation of natural antioxidants from brown algae.

Objective: To investigate the role and mechanism of miR-17-5p in cerebral hypoxia/reoxygenation (H/R)-induced apoptosis., Methods: The present study used human brain microvascular endothelial cells (HBMVECs) to establish cerebral H/R model. MTT was used to measure the cell viability. Flow cytometry was used to detect the cell apoptosis. The interaction between miR-17-5p and PTEN was determined using dual luciferase reporter assay. RT-qPCR and Western blotting were used for determination of the expression of miR-17-5p, PTEN, apoptosis- and PI3K/AKT/mTOR signalling-related proteins., Results: The cell viability and the expression of miR-17-5p were obviously down-regulated while the expression of PTEN was obviously up-regulated in H/R cells. The cell viability was remarkably enhanced, and the cell apoptosis induced by H/R injury was dramatically reduced when miR-17-5p was overexpressed in HBMVECs under H/R condition, which was reversed by overexpression of PTEN. Dual luciferase reporter assay showed PTEN was a direct target of miR-17-5p. Treatment of PI3K inhibitor LY294002 significantly increased the apoptosis rate of HBMVECs, and this effect was significantly reversed by transfection of miR-17-5p mimics, while further dramatically enhanced by overexpression of PTEN., Conclusion: MiR-17-5p could ameliorate cerebral I/R injury-induced cell apoptosis by directly targeting PTEN and regulation of PI3K/AKT/mTOR signalling.

Objectives: This study aimed to quantify left ventricular (LV) myocardial strain and torsion in patients with type 2 diabetes mellitus (T2DM) and evaluate their systolic and diastolic function using conventional and speckle tracking echocardiography. Methods: Forty-seven patients with T2DM were divided into a group without microvascular complications (the DM A group) and a group with microvascular complications (the DM B group), while another 27 healthy participants acted as the control group. All the participants had had an echocardiography examination. All the original data were imported into EchoPAC workstation for the analysis and quantification of LV strain and torsion. Results: Compared with the control group, the LV end-diastolic volume, end-systolic volume, and ejection fraction of the DM A and DM B groups showed no significant differences, but the global longitudinal strain and the global circular strain were reduced in the DM B group. There were significant differences in the left ventricular relative wall thickness (RWT), left ventricular mass index (LVMI), the early mitral valvular blood flow velocity peak/left ventricular sidewall mitral annulus late peak velocity, left ventricular sidewall mitral annulus early peak velocity/left ventricular sidewall mitral annulus late peak velocity, isovolumic relaxation time, peak twisting, peak untwisting velocity (PUV), untwisting rate (UntwR), time peak twisting velocity (TPTV), and time peak untwisting velocity (TPUV) between the DM A, DM B, and control groups. While the peak twisting velocity (PTV) was slower in the DM B group compared with the control group, the RWT, PTV, PUV, UntwR, TPTV, and TPUV in the DM B group were significantly different from the DM A group. Conclusion: The cardiac function of patients with T2DM in its early stages, when there are no microvascular complications, could be monitored with the analysis of two-dimensional strain and torsion., 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 Yang, Fang, Chen, Lv and Kang.)

In this paper, the effects of an aging treatment on the corrosion resistance/mechanism of a tensile deformed Al-Cu-Mn-Fe-Zr alloy are investigated. The impedance magnitude and polarization resistance increase, while the corrosion current decreases with the increased aging time and temperature. The discontinuously-distributed precipitates and precipitation-free zone, which can cut the corrosion channels, appear at grain boundaries when the temperature is relatively high and the aging time is relatively long. They can improve the corrosion resistance. Additionally, the intergranular and pitting corrosion are the main mechanisms. The intergranular corrosion is likely to occur in an under-aged alloy. This is because the potential difference between the grain boundaries and grains is high, due to the segregation of Cu atoms. When the aging degree is increased, the grain boundary precipitates reduce the potential difference, and the intragranular precipitates make the surrounding matrix prone to dissolution. As such, the pitting corrosion is likely to occur in the over-aged alloys.

In this work, the physicochemical properties of maleic anhydride (MAH)-modified κ-carrageenan (κCar) (MC) were characterized and compared with those of native κ-carrageenan (NC). The Fourier transform infrared spectrum of MC exhibited that κCar was successfully modified. Thermogravimetric analysis indicated that the thermal stability of MC was decreased. When the degree of substitution was 0.032, MC exhibited a low gel strength (759 g/cm 2 ), gelling temperature (33.3 °C), and dehydration rate (60.3%). Given the excellent film-forming ability of κCar, MC films were then prepared and were found to have better mechanical and barrier properties (UV and water) than NC films. With regard to optical properties, MC films could completely absorb UV light in the range of 200-236 nm. The water contact angle of MC films was higher than that of NC films. Moreover, the elongation at break increased from 26.9% to 163%. These physicochemical property changes imply that MC can be employed in polysaccharide-based films.

In this work, a non-toxic chitosan-based carrier was constructed via genipin activation and applied for the immobilization of tannase. The immobilization carriers and immobilized tannase were characterized using Fourier transform infrared spectroscopy and thermogravimetric analysis. Activation conditions (genipin concentration, activation temperature, activation pH and activation time) and immobilizations conditions (enzyme amount, immobilization time, immobilization temperature, immobilization pH, and shaking speed) were optimized. The activity and activity recovery rate of the immobilized tannase prepared using optimal activation and immobilization conditions reached 29.2 U/g and 53.6%, respectively. The immobilized tannase exhibited better environmental adaptability and stability. The immobilized tannase retained 20.1% of the initial activity after 12 cycles and retained 81.12% of residual activity after 30 days storage. The catechins composition analysis of tea extract indicated that the concentration of non-ester-type catechins, EGC and EC, were increased by 1758% and 807% after enzymatic treatment. Biological activity studies of tea extract revealed that tea extract treated with the immobilized tannase possessed higher antioxidant activity, higher inhibitory effect on α-amylase, and lower inhibitory effect on α-glucosidase. Our results demonstrate that chitosan activated with genipin could be an effective non-toxic carrier for tannase immobilization and enhancing biological activities of tea extract.

Inflammation is a critical player in the development and progression of colon cancer. Basic leucine zipper transcription factor ATF-like 3 (BATF3) plays an important role in infection and tumor immunity through regulating the development of conventional type 1 dendritic cells (cDC1s). However, the function of BATF3 in colitis and colitis-associated colon cancer (CAC) remains unclear. Here, BATF3 wild-type and knockout mice were used to construct an AOM/DSS-induced CAC model. In addition, DSS-induced chronic colitis, bone marrow cross-transfusion (BMT), neutrophil knockout, and other animal models were used for in-depth research. We found that BATF3 deficiency in intestinal epithelial cells rather than in cDC1s inhibited CAC, which was depended on inflammatory stimulation. Mechanistically, BATF3 directly promoted transcription of CXCL5 by forming a heterodimer with JunD, and accelerated the recruitment of neutrophils through the CXCL5-CXCR2 axis, ultimately increasing the occurrence and development of CAC. Tissue microarray and TCGA data also indicated that high expression of BATF3 was positively correlated with poor prognosis of colorectal cancer and other inflammation-related tumors. In summary, our results demonstrate that intestinal epithelial-derived BATF3 relies on inflammatory stimulation to promote CAC, and BATF3 is expected to be a novel diagnostic indicator for colitis and CAC.

Tannase is widely used in tea beverage processing because of its ability to catalyze the hydrolysis of hydrolysable tannins or gallic acid esters and effectively improve the quality of tea extracts through enzymatic extraction. A new thermophilic tannase was cloned from Aspergillus niger FJ0118 and characterized. The tannase exhibited an optimal reaction temperature of 80 °C and retained 89.6% of the initial activity after incubation at 60 °C for 2 h. The enzymatic extraction of green tea at high temperature (70 °C) for a short time (40 min) was devised on the basis of the superior thermal stability of tannase. The enzymatic reaction significantly increased the total polyphenol content of green tea extract from 137 g·kg -1 to 291 g·kg -1 . The enzymatic reaction effectively degraded the ester catechins into non-ester catechins compared with the water extraction method. Results suggested that the thermally stable tannase exhibited potential applications in the enzymatic extraction of green tea beverage.

Objective: To investigate the effects of human amniotic mesenchymal stem cell（AMSC） on acute graft-versus-host disease (aGVHD) in xenotransplatation., Methods: NPG mice were injected with human PBMNC via tail vein to establish a xenografted aGVHD model. The mice in the experimental group were divided into PBMNC infusion group and PBMNC+AMSC co-infusion group, the general condition, survival time and manifestations of aGVHD were observed, the body weight and blood routine indicators were detected, the pathological changes of aGVHD target organs (lung, liver, spleen, small intestine) were observed by HE staining, and the levels of human T cells in peripheral blood, tissues and organs of mice was detected by flow cytometry., Results: The manifestations of aGVHD (lassitude hunchback, shrub, weight reduction, etc.) and the pathological damage of the target organs (lung, liver, spleen, intestine) in PBMNC+AMSC co-infusion group were lighter than those in PBMNC infusion group. Moreover, the PBMNC and AMSC co-infusion significantly reduced the implantion proportion of human T lymphocytes (CD3 + , CD45 + ) in mice and increased the ratio of CD4 + /CD8 + ., Conclusion: Infusion of human-derived AMSC can attenuate the manifestations of aGVHD in mouse xenografts to a certain level, and improve the pathological damage of receptor target organs.

Alginate extracted from widely cultured brown seaweed can be hydrolyzed by alginate lyase to produce alginate oligosaccharides (AOS) with intriguing biological activities. Herein, a novel alginate lyase Aly1281 was cloned from marine bacterium Pseudoalteromonas carrageenovora ASY5 isolated from mangrove soil and found to belong to polysaccharide lyase family 7. Aly1281 exhibited maximum activity at pH 8.0 and 50 °C and have broad substrate specificity for polyguluronate and polymannuronate. Compared with other alginate lyases, Aly1281 exhibited high degradation specificity and mainly produced di-alginate oligosaccharides which displayed good antioxidant function to reduce ferric and scavenge radicals such as hydroxyl, ABTS + and DPPH. Moreover, the catalytic activity and kinetic performance of Aly1281 were highly improved with the addition of salt, demonstrating a salt-activation property. A putative conformational structural feature of Aly1281 was found by MD simulation analysis for understanding the salt-activation effect., Competing Interests: The authors declare no competing financial interest.

Background: Carcinoid syndrome is associated with a reduced quality of life that can be attributed to symptoms such as diarrhea and fatigue as well as social and financial issues. This study was conducted to psychometrically assess meaningful change in bowel movement frequency among carcinoid syndrome patients using data from the TELESTAR clinical study., Methods: An anchor-based approach for deriving meaningful change thresholds consisted of mapping change from baseline bowel movement frequency to other patient-reported assessments of change. These included the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core Questionnaire (QLQ-C30) Diarrhea Symptom responders, the EORTC Gastrointestinal NET questionnaire (GI.NET21) GI Symptom responders, and reported adequate relief at Week 12 (≥ 10-point score decrease from Day 1 to Week 12). Parameters included within-group mean change from baseline to Week 12, t-tests of the change (Wilcoxon rank sum for adequate relief), and effect size., Results: There were 135 carcinoid syndrome patients with a mean baseline frequency of 5.7 bowel movements a day. A distribution-based method yielded meaningful change estimates of 0.62 bowel movements a day for overall frequency and 0.83 bowel movements a day at Week 12. Anchor-based analysis indicated a large effect size among patients who reported adequate relief at Week 12 (- 1.58; n = 18; P = 0.014), the QLQ-C30 Diarrhea domain responders (- 1.24; n = 40; P < 0.001), and the GI.NET21 GI Symptoms Domain responders (- 1.49; n = 25; P = 0.005). Exit interview data for meaningful change yielded effect size estimates of - 1.57 for overall change during the Double-blind Treatment Period and - 1.97 for change between Baseline and Week 12., Conclusions: Meaningful change derivation is critical to interpret patient outcomes for evaluating treatment efficacy. In this study, carcinoid syndrome patients experienced clinically meaningful reductions in bowel movement frequency of ≥30% over 12 weeks with telotristat ethyl treatment., Trial Registration: NCT01677910 .

Objective: To analyze the image features of shear wave elastrography (SWE) in breast masses, and to evaluate their values in the differentiation of benign and malignant breast lesions. Methods: A total of 361 patients with 403 breast lesions who simultaneously underwent conventional ultrasound and SWE examination from February 2015 to January 2018 were selected. Diagnosis in all patients was confirmed by aspiration biopsy or operative pathology. The SWE images were collected and the elastic images were divided into 5 types. The SWE image features of different breast pathological types were summarized, and their values in benign and malignant breast lesion diagnoses were evaluated. Results: The main features of benign breast lesion were type Ⅰ and Ⅱ, the main features of the malignant lesion were type Ⅳ and Ⅴ, and the proportion of which were 43.6% (71/163), 37.4% (61/163), 22.1% (53/240) and 57.9% (139/240), respectively. Type Ⅲ accounted for a certain proportion in both benign and malignant lesions. The SWE image features of benign and malignant lesions were compared and a significant difference was observed ( P <0.001). The type Ⅴ features were mainly observed in invasive ductal carcinoma, invasive lobular carcinoma and other types of invasive carcinoma, while the type Ⅳ features were mostly presented in ductal carcinoma in situ and mucinous carcinoma. Fibroadenoma, fibroadenosis accompanied with fibroadenoma, and fibroadenosis were featured with type Ⅰ. Both intraductal papilloma and benign phyllodes tumor were mostly type Ⅱ, while type Ⅲ and Ⅴ were more common in chronic granulomatous mastitis. When type Ⅰ and typeⅡof breast lesions were classified as benign features while type Ⅳ and Ⅴ were malignant features, the sensitivity and specificity of breast malignant lesion diagnosis were 91.2% and 84.7% by application of SWE combined with breast imaging reporting and data system (BI-RADS). The sensitivity of combined diagnosis was slightly lower than that of conventional ultrasound ( P >0.05), but the specificity was significantly higher than conventional ultrasound ( P <0.01). Conclusion: The SWE is a simple and effective method. Combination of SWE with conventional ultrasound may improve the diagnostic differentiation of benign and malignant breast lesions.

Biothiols play critical roles in many biological processes and their aberrant is related to a variety of syndromes. A simple and reliable colorimetric method is developed in this work for biothiols detection based on an oxidase mimic, a metal organic framework (MOF) MIL-53(Fe), and a peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB). In this design, MIL-53(Fe) is utilized to catalyze the conversion of TMB to a blue colored 3,3',5,5'-tetramethylbenzidine diimine, which can be read on a spectrophotometer at 652 nm. The oxidation-induced blue color generation can be efficiently inhibited by biothiols, thus a colorimetric analytical method is proposed for biothiols detection based on the above system. Under optimal conditions, a linear relationship in a range from 1 to 100 μM and a limit of detection (LOD) at 120 nM are achieved with Cys as a model target. The developed platform is further applied to evaluate cellular biothiols in normal (RWPE-1) and cancer (LNCap) cell lines, revealing that the overall biothiols level in LNCap is much higher than that in RWPE-1. This work renders a powerful tool for identifying cancer cells in a simple manner for biomedical diagnosis associated with biothiols., (Copyright © 2019. Published by Elsevier Inc.)

Plantago asiatica L. seeds is a common folk medicine with a long history of medical use in China because of its antipyretic, diuretic, and expectorant properties. It has been applied to treat hypertension clinically due to its diuresis, however, its efficacy and mechanisms on anti-hypertension has not been reported yet to our knowledge. In this study, we investigated the antihypertensive effect and underlying mechanisms of P. asiatica L. seeds extract (PASE) in spontaneously hypertensive rat (SHR). Male SHRs were treated with 2.5 mg/kg of fosinopril (FOS) and 400 mg/kg of PASE orally per day for once or 12 weeks. SHR or Wistar-Kyoto rats (WKY) receiving vehicle (distilled water) was used as control. The results demonstrated systolic, diastolic, and mean blood pressures (SBP, DBP, and MBP) were significantly lowered after single and long-term intragastric administration of PASE. The cardiac and aortic index and collagen accumulation were improved in the PASE group compared with the SHRs group. Meanwhile, PASE treatment remarkably reduced urine total protein, the ratio of serum urea nitrogen to serum creatinine, and increased serum potassium. The levels of serum angiotensin I (Ang I), angiotensin II (Ang II), the ratio of Ang II to Ang I, and aldosterone (ALD) were lowered after treatment of PASE. Besides, PASE and its major active constituents of phenylethanoid glycosides, including isoacteoside, plantamajoside and acteoside, were found to effectively inhibit angiotensin-converting enzyme (ACE) activation in vitro . These findings suggest that PASE has the antihypertensive effect that may involve a mechanism of ACE inhibition and simultaneously protect organ damage against hypertension.

Objective: To evaluate the clinical efficacy of umbilical moxibustion in the treatment of patients with idiopathic pulmonary interstitial fibrosis complicated with gastroesophageal reflux of lung-spleen qi deficiency., Methods: A total of 116 patients with idiopathic pulmonary fibrosis complicated with gastroesophageal reflux of lung spleen-deficiency were randomized into an observation group (58 cases) and a control group (58 cases). In the control group, the routine treatment was applied; in the observation group, on the base of the treatment as the control group, the umbilical moxibustion was used. The treatment was given 2 times a week, 2 h each time for 12 weeks, and followed up for 12 weeks after treatment. The composite physiological indicators (CPI), TCM syndrome scores, the St. George respiratory questionnaire score (SGRQ) and 6-minute walk test (6MWT) were compared before and after treatment in the two groups., Results: The improvement of the TCM syndrome scores (cough, post-activity shortness of breath, fatigue, heartburn, acid reflux), CPI score and 6MWT in the observation group was better than those in the control group (all P <0.05). There was no significant difference in the scores of SGRQ scale between the two groups after treatment ( P >0.05). There was no significant difference in the scores of CPI scores and syndromes (cough and fatigue) between the two groups at 12 weeks after treatment (all P >0.05). The 6MWT, SGRQ scale scores and syndrome scores (post-activity shortness of breath, acid reflux, heartburn) were better than those in the control group in the follow up (all P <0.05)., Conclusion: Umbilical moxibustion can improve the ventilation and diffusion function of lung in patients with idiopathic pulmonary fibrosis and gastroesophageal reflux of lung-spleen qi deficiency, reduce clinical symptoms and improve patients' quality of life and activity endurance. And it has long-term effect.

Excessive activated T-cell proliferation was observed in vivo in one patient after an anti-CD19-chimeric antigen receptor (CAR) T-cell infusion. The patient, who had chemotherapy refractory and CD19 + diffuse large B-cell lymphoma (DLBCL), received an anti-CD19 CAR T-cell infusion following conditioning chemotherapy (fludarabine/cyclophosphamide). The lymphocyte count in the peripheral blood (PB) increased to 77 × 10 9 /L on day 13 post infusion, and the proportion of CD8 + actived T cells was 93.06% of the lymphocytes. Then, the patient suffered from fever and hypoxaemia. Significant increases in serum cytokine, lactate dehydrogenase, aspartate aminotransferase (AST), alanine transaminase (ALT), and glutamic-oxalacetic transaminase (γ-GT) levels were observed. A high-throughput sequencing analysis for T-cell receptors (TCRs) and whole-genome sequencing were used to explore the mechanisms underlying this excessive T-cell proliferation. TCR diversity was demonstrated, but no special gene mutation was found. The patient was found to be infected with the John Cunningham polyomavirus (JCV). It cannot be ruled out the bystander activation pathway induced by JCV infections related the excessive activated T-cell proliferation. Although the clinical and laboratory data do not fully explain the reason for excessive T-cell proliferation after the anti-CD19 CAR T-cell infusion, the risk of this type of toxicity should be emphasized. This study was registered at www.clinicaltrials.gov as NCT01864889.

Purpose: In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m 2 ) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival., Methods: Assessment of the occurrence of weight change ≥3% at week 12 was prespecified in the statistical analysis plan., Findings: In 120 patients with weight data available, weight gain ≥3% was observed in 2 of 39 patients (5.1%) taking placebo TID, 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss ≥3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status., Implications: Up to 32.5% of patients treated with telotristat ethyl experienced significant, dose-dependent weight gain, associated with reduced diarrhea severity and improved biochemical and metabolic parameters. Improved nutritional status could be an additional aspect of telotristat ethyl efficacy among patients with functioning metastatic neuroendocrine tumors. ClinicalTrials.gov identifier: NCT01677910., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of 810 nm near-infrared (NIR) laser on the revascularization of ischemic flaps., Background: It has long been proved that photobiomodulation therapy (PBMT) improves the blood supply of flaps. NIR laser improves the treatment of hypodermis-located lesions and of flap survival, but basic research on the use of 810 nm NIR laser for ischemic flap revascularization is still lacking., Materials and Methods: We prepared two symmetrical long random-pattern flaps on the backs of 60 rats. Each flap was 6 cm long, 1 cm wide, and 1 cm to the middle line. The flaps were divided into an irradiated flap group and an internal control group. The irradiated flaps underwent postoperative 810 nm laser therapy with the energy density of 11.30 J/cm 2 daily. The control flaps were covered by stainless steel to avoid laser irradiation. We observed the viability of the flaps. The flaps underwent Hematoxylin and Eosin (H&E) staining for the observation of histomorphology, immunohistochemical staining of factor VIII for the capillary count, α-smooth muscle actin for the small arterial count, and vascular endothelial growth factor for the integrated optical density (OD) of the positive stained color., Results: The irradiated flaps showed significantly better flap survival than the control flaps. H&E staining showed that the irradiated flaps had clear tissue structure and little inflammatory cell infiltration. The control flaps demonstrated comparatively worse results. Vascular endothelial growth factor staining showed that the difference in integrated OD between the irradiated flaps and the control flaps was not statistically significant. α-smooth muscle actin and factor VIII staining showed significantly greater numbers of arterioles and capillaries in the irradiated flaps than the control flaps after 4 days of irradiation., Conclusions: PBMT with 810 nm NIR laser could enhance ischemic flap revascularization and increase flap viability.

Expressed by cancer stem cells of various epithelial cell origins, CD133 is an attractive therapeutic target for cancers. Autologous chimeric antigen receptor-modified T-cell directed CD133 (CART-133) was first tested in this trial. The anti-tumor specificity and the postulated toxicities of CART-133 were first assessed. Then, we conducted a phase I clinical study in which patients with advanced and CD133-positive tumors received CART-133 cell-infusion. We enrolled 23 patients (14 with hepatocellular carcinoma [HCC], 7 with pancreatic carcinomas, and 2 with colorectal carcinomas). The 8 initially enrolled patients with HCC were treated by a CART-133 cell dose escalation scheme (0.05-2 × 10 6 /kg). The higher CAR-copy numbers and its reverse relationship with the count of CD133+ cells in peripheral blood led to the determination of an acceptable cell dose is 0.5-2 × 10 6 /kg and reinfusion cycle in 23 patients. The primary toxicity is a decrease in hemoglobin/platelet (≤ grade 3) that is self-recovered within 1 week. Of 23 patients, three achieved partial remission, and 14 achieved stable disease. The 3-month disease control rate was 65.2%, and the median progression-free survival was 5 months. Repeated cell infusions seemed to provide a longer period of disease stability, especially in patients who achieved tumor reduction after the first cell-infusion. 21 out of 23 patients had not developed detectable de novo lesions during this term. Analysis of biopsied tissues by immunohistochemistry showed CD133+ cells were eliminated after CART-133 infusions. This trial showed the feasibility, controllable toxicities, and effective activity of CART-133 transfer for treating patients with CD133-postive and late-stage metastasis malignancies.

Tumor metastasis is the leading cause of death in patients with advanced gastric cancer (GC). Limited therapeutic regimens are available for this condition, which is associated with a poor prognosis, and the mechanisms underlying tumor metastasis remain unclear. In the present study, increased histone methyltransferase G9A expression in GC tissues correlated with advanced stage and shorter overall survival, and in vitro and in vivo experiments revealed that G9A promoted tumor invasion and metastasis. Moreover, we observed that Reg IV induced G9A via the p-ERK/p-SP1 pathway. SP1 directly binds the G9A promoter and enhances G9A expression, and upregulated G9A then forms a transcriptional activator complex with P300 and GR, thereby promoting ITGB3 expression induced by dexamethasone (DEX) and contributing to GC metastasis. However, the G9A-mediated increase in ITGB3 expression was not dependent on the SET domain and methyltransferase activity of G9A. This study demonstrates that G9A is an independent prognostic marker and promotes metastasis in GC, thus suggesting that it may be a tumor biomarker and potential therapeutic target in GC.

Thermal degradation kinetics of lutein, zeaxanthin, β-cryptoxanthin, β-carotene was studied at 25, 35, and 45°C in a model system. Qualitative and quantitative analyses of all-trans- and cis-carotenoids were conducted using HPLC-DAD-MS technologies. Kinetic and thermodynamic parameters were calculated by non-linear regression. A total of 29 geometrical isomers and four oxidation products were detected, including all-trans-, keto compounds, mono-cis- and di-cis-isomers. Degradations of all-trans-lutein, zeaxanthin, β-cryptoxanthin, and β-carotene were described by a first-order kinetic model, with the order of rate constants as k β -carotene >k β -cryptoxanthin >k lutein >k zeaxanthin . Activation energies of zeaxanthin, lutein, β-cryptoxanthin, and β-carotene were 65.6, 38.9, 33.9, and 8.6kJ/moL, respectively. cis-carotenoids also followed with the first-order kinetic model, but they did not show a defined sequence of degradation rate constants and activation energies at different temperatures. A possible degradation pathway of four carotenoids was identified to better understand the mechanism of carotenoid degradation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The aim of the current study was to identify potential biomarkers of childhood obesity, and investigate molecular mechanisms and candidate agents in order to improve therapeutic strategies for childhood obesity. The GSE9624 gene expression profile was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) in omental adipose tissues were analyzed with limma package by comparing samples from obese and normal control children. Two‑way hierarchical clustering was applied using the pheatmap package. The co‑expression (CE) analysis was performed using online CoExpress software. Subsequent to functional classification via the GOSim package, the gene network enriched by DEGs was visualized using the Cytoscape package. The codon usage bias of the DEGs was then examined using the CAI program from the European Molecular Biology Open Software Suite. In total, 583 DEGs (273 upregulated genes and 310 downregulated genes) were observed in the omental adipose tissues between samples from obese and normal control children. Hierarchical clustering identified a significant difference between samples from obese and normal control children. Subsequent to CE analysis, 130 DEGs, which were classified into 4 clusters, were selected. The following 3 upregulated and 2 downregulated genes were identified to be significant: Upregulated genes, microtubule‑associated protein tau (MAPT), destrin (actin depolymerizing factor) (DSTN) and spectrin, β, non‑erythrocytic 1 (SPTBN1); downregulated genes, Rho/Rac guanine nucleotide exchange factor 2 (ARHGEF2) and spindle and kinetochore associated complex subunit 1 (SKA1). The top 3 amino acids were identified to be glycine, leucine and serine with a high bias. The DEGs MAPT, DSTN, SPTBN1, ARHGEF2 and SKA1 are suggested to be candidate biomarkers for childhood obesity.

Purpose: Telotristat ethyl, an oral tryptophan hydroxylase inhibitor, is intended to treat carcinoid syndrome by reducing serotonin production. Telotristat ethyl was evaluated in TELESTAR, a Phase III study for patients who had carcinoid syndrome with at least 4 bowel movements (BMs) per day and who were receiving somatostatin analogue therapy. This interview substudy was conducted to provide insight into the patient experience in TELESTAR and to help understand whether reductions in BM frequency (the primary end point) and other symptoms were clinically meaningful., Methods: Participating sites were asked to invite (before randomization) all eligible patients to telephone interviews scheduled at the end of the double-blind treatment period. Patients and interviewers were blinded to treatment., Findings: All 35 interviewed participants reported diarrhea and/or excessive BMs at baseline. Patients reported that these symptoms negatively affected emotional, social, physical, and occupational well-being. Prespecified criteria for treatment response (achieving ≥30% reduction in BM frequency for at least 50% of the days) were met by 8 of 26 patients taking telotristat ethyl and 1 of 9 patients taking placebo. All 8 patients taking telotristat ethyl described clinically meaningful reductions in BM frequency and were very satisfied with the ability of the study drug to control their carcinoid syndrome symptoms. Overall, reports of being very satisfied were observed in 12 patients taking telotristat ethyl and 0 taking placebo., Implications: Patient interviews revealed that TELESTAR patients, at baseline, were significantly affected by their high BM frequency. Patient reports of their clinical trial experience supported the significance of the primary end point and clinical responder analysis in TELESTAR, helping identify and understand clinically meaningful change produced by telotristat ethyl., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

The chemical constituents of Plantaginis Semen with hypoglycemic effect was investigated in this paper. The previous results of the in vivo hypoglycemic effect showed that 60% ethanol extract of Plantaginis Semen decreased the levels of FBG and improved the glucose tolerance in high fat diet(HFD)-induced diabetic C57BL/6 mice. Then, in the present study, the above potential bioactive extract was separated and purified by silica gel, ODS, Sephadex LH-20 column chromatography, medium pressure liquid chromatography(MPLC)and preparative HPLC. The structures of isolated compounds were identified by physicochemical properties and spectral analyses. Eight compounds were obtained and identified as 4, 4a, 5, 7a-tetrahydro-7-(hydroxymethyl)cyclopenta[c]pyran-3(1H)-one(1), iridolactone(2), pedicularislacton(3), rehmaglutin C(4), geniposidic acid(5), p-hydroxylphenylglycerol(6), 1, 2-benzenediol-4-(2-hydroxyethyl)(7), and 3-buten-2-one-4-[3-(β-D-glucopyranosyloxy)-4-hydroxyphenyl](8). Among them, compounds 1-5 were iridoids, and 6-8 were phenolic acids. Compound 1 was a new natural product, and compounds 2-4, 6 and 8 were isolated from the Plantaginaceae family for the first time., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)