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Kaempferol (KF) is an important natural anti-inflammatory flavonol. Acute pancreatitis (AP) is an inflammatory disorder, which in about 20% cases may develop into severe acute pancreatitis (SAP) with a high mortality rate. This research was to study the effects and mechanism of kaempferol on SAP. SAP was induced by sodium taurocholate. The level of cytokines was analyzed by enzyme-linked-immunosorbent serologic assay. The expression of nuclear factor kappa B (NF-κB) and Kelch-like ECH-associated protein 1–nuclear factor erythroid 2-related factor 2 (Keap1–Nrf2) proteins was analyzed by Western blot assay. Pathological changes in the pancreas were evaluated by hematoxylin and eosin staining. Kaempferol attenuated pancreatic injury in SAP rats, including reduction in inflammatory infiltration and necrosis. The level of serum amylase and lipase was also decreased in kaempferol-treated SAP rats. Kaempferol inhibited the expression of inflammatory mediators (nuclear factor-α, Interlukin-1β, and Interlukin-6), and alleviated the oxidative stress characterized by the decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) levels. Kaempferol decreased the expression of cleaved caspase 3 and anti-apoptotic protein Bcl-2, which indicated that kaempferol could inhibit apoptosis of pancreatic cells in SAP rats. Kaempferol treatment could decrease the expression of p-p65 and the amount of nuclear Nrf2 (Nu-Nrf2), which demonstrated that kaempferol inhibited the NF-κB activation and enhanced the Keap1–Nrf2 pathway. Our research indicated that kaempferol could attenuate the pancreatic injury of SAP by regulating NF-κB and Keap1–Nrf2 signaling pathway. Kaempferol could serve as a natural candidate for treating SAP.

Although activation of hepatic stellate cells (HSCs) plays a central role in the development of liver fibrosis, the mechanism underlying the activation of HSCs remains unclear. Keratin 17 (KRT17), a member of the intermediate filament family, can regulate tumor cell proliferation and migration. The current study aimed to elucidate the role of KRT17 in the activation of HSCs and the mechanisms underlying liver fibrosis.The expression of KRT17 was determined using immunohistochemistry in tissue microarray. Western blotting and qRT-PCR assays were used to determine the KRT17 expression in fibrotic liver tissues obtained from human subjects and mice. LX-2 cells were treated with TGF-β1 recombinant protein and adipocyte differentiation mixture (MDI) mix to induce and reverse LX-2 cell activation, respectively, in order to explore the correlation between KRT17 and HSC activation. Additionally, cell proliferation and migration abilities of LX-2 cells transfected with KRT17-overexpressing plasmid or small interfering RNA were determined using CCK-8, flow cytometry, Transwell, and wound healing assays. Finally, rescue assay was used to explore the role of KRT17 in HSC activation and epithelial-mesenchymal transition (EMT).The expression of KRT17 was higher in the human and mouse fibrotic liver tissues than in healthy liver tissues, and it was positively correlated with HSC activation. Upregulated KRT17 enhanced proliferation, migration, HSC activation and EMT in LX-2 cells, while knockdown of KRT17 reversed these effects. TGF-β1 recombinant protein accelerated KRT17-mediated EMT, HSC activation and proliferation, while TGF-β1 inhibitor counteracted the effect of KRT17KRT17 promoted HSC activation, proliferation and EMT in hepatic fibrosis probably via TGF-β1 signaling, and KRT17 might serve as a therapeutic target for the treatment of liver fibrosis.

BACKGROUND The longitudinal association between persistent moderate to severe pain and subsequent long-term cognitive decline remains inconclusive. METHODS Study population came from the English Longitudinal Study of Ageing, an ongoing prospective and nationally representative cohort of community-dwelling adults aged ≥50 years in England. At waves 1 (2002/2003) and 2 (2004/2005) of the study, pain severity was measured based on pain intensity scores ranged from 0 to 10. We defined moderate to severe pain as pain intensity scores ≥5 points. Persistent moderate to severe pain was defined as participants reported moderate to severe pain at both waves 1 and 2. Standardized global cognitive Z scores derived from verbal memory, temporal orientation and semantic fluency were used as the primary outcome. RESULTS A total of 6,869 individuals (3,896 women; mean age: 63.9 ± 9.5 years) who have accepted twice measurements of pain at waves 1 and 2 (baseline), and at least one reassessment of cognitive function at waves 3 (2006/2007) to 8 (2016/2017), were included in this study. Each 5-point increase in the sum of pain intensity scores was associated with a faster rate of -0.009 (95% CI: -0.013 to -0.006, p

Chronic actinic dermatitis (CAD) is a common debilitating photodermatosis. Patients often have to completely avoid outdoor activities, which severely impacts their quality of life. Phototherapy is effective for CAD and seems to increase patients' tolerance towards sunlight and consequently decrease the extent of disease. Unfortunately, the slower onset and time-consuming nature of phototherapy limits the clinical application. Considering the effectiveness and time-saving nature of ultraviolet (UV)-A rush hardening in solar urticaria, we performed a pilot study to determine whether UV-A rush hardening is effective in CAD. Six patients with CAD were exposed to multiple sessions of UV-A for 4-5 days at 1-h intervals/day. Subsequently, maintenance UV-A exposure was performed at 1-2-week intervals. Phototesting at baseline showed that three patients were sensitive to both UV-A and -B, and the other three patients only showed UV-A sensitivity. All of the patients responded well to UV-A rush hardening and four (67%) maintained a good remission status after 1 year. The results of this pilot study suggest that UV-A rush hardening phototherapy is effective and well tolerated in the treatment of CAD, while future larger prospective studies using objective scores of disease activity and quality of life are needed.

Background: Surgical treatment of both-column acetabular fractures is challenging because of the complex acetabular fracture patterns and the curved surface of the acetabulum. Seldom study has compared the application of three-dimensional (3D) printing technology and traditional methods of contouring plates intra-operatively for the surgical treatment of both-column acetabular fractures. We presented the use of both 3D printing technology and a virtual simulation in pre-operative planning for both-column acetabular fractures. We hypothesized that 3D printing technology will assist orthopedic surgeons in shortening the surgical time and improving the clinical outcomes. Methods: Forty patients with both-column acetabular fractures were recruited in the randomized prospective case-control study from September 2013 to September 2017 for this prospective study (No. ChiCTR1900028230). We allocated the patients to two groups using block randomization (3D printing group, n = 20; conventional method group, n = 20). For the 3D printing group, 1:1 scaled pelvic models were created using 3D printing, and the plates were pre-contoured according to the pelvic models. The plates for the conventional method group were contoured during the operation without 3D printed pelvic models. The operation time, instrumentation time, time of intra-operative fluoroscopy, blood loss, number of times the approach was performed, blood transfusion, post-operative fracture reduction quality, hip joint function, and complications were recorded and compared between the two groups. Results: The operation and instrumentation times in the 3D printing group were significantly shorter (130.8 ± 29.2 min, t = －7.5, P < 0.001 and 32.1 ± 9.5 min, t = －6.5, P < 0.001, respectively) than those in the conventional method group. The amount of blood loss and blood transfusion in the 3D printing group were significantly lower (500 [400, 800] mL, Mann-Whitney U= 74.5, P < 0.001 and 0 [0,400] mL, Mann-Whitney U = 59.5, P < 0.001, respectively) than those in the conventional method group. The number of the approach performed in the 3D printing group was significantly smaller than that in the conventional method group (pararectus + Kocher-Langenbeck [K-L] approach rate: 35% vs. 85%; x2 = 10.4, P < 0.05). The time of intra-operative fluoroscopy in the 3D printing group was significantly shorter than that in the conventional method group (4.2 ± 1.8 vs. 7.7 ± 2.6 s; t = －5.0, P < 0.001). The post-operative fracture reduction quality in the 3D printing group was significantly better than that in the conventional method group (good reduction rate: 80% vs. 30%; x2 = 10.1, P < 0.05). The hip joint function (based on the Harris score 1 year after the operation) in the 3D printing group was significantly better than that in the conventional method group (excellent/good rate: 75% vs. 30%; x2 = 8.1, P < 0.05). The complication was similar in both groups (5.0% vs. 25%; x2 = 3.1, P = 0.182). Conclusions: The use of a pre-operative virtual simulation and 3D printing technology is a more effective method for treating bothcolumn acetabular fractures. This method can shorten the operation and instrumentation times, reduce blood loss, blood transfusion and the time of intra-operative fluoroscopy, and improve the post-operative fracture reduction quality. Clinical trail registration: No.ChiCTR1900028230; http://www.chictr.org.cn Key words: Both-column; Acetabulum fractures; Computer simulation; Three-dimensional printing; Internal fracture fixation

Innate lymphoid cells (ILCs) are a group of lymphocytes without diversified antigen receptors encoded by gene rearrangement on T and B cells. ILCs, which are tissue-resident innate immune cells, expressed particularly in the mucosa or the barrier surface, contribute to the formation of lymphoid organs, the maintenance of tissue homeostasis, and the regulation of antimicrobial defenses. It has been recently reported that ILCs were enriched at the maternal–fetal interface. During a successful pregnancy, the maternal immune system must tolerate a fetus as an allograft. With the new defined of ILCs, a number of studies have shown that three types of ILCs are involved in embryonic development and pregnancy maintenance as well as the occurrence and development of pregnancy-related complications. This article reviews the types and roles of ILCs in normal pregnancy and pregnancy-related diseases.

Hypoxia‐inducible factor 1α (HIF‐1α) plays a critical role in the apoptotic process during cardiac ischaemia/reperfusion (I/R) injury. This study aimed to investigate whether post‐treatment with dexmedetomidine (DEX) could protect against I/R‐induced cardiac apoptosis in vivo and in vitro via regulating HIF‐1α signalling pathway. Rat myocardial I/R was induced by occluding the left anterior descending artery for 30 minutes followed by 6‐hours reperfusion, and cardiomyocyte hypoxia/reoxygenation (H/R) was induced by oxygen‐glucose deprivation for 6 hours followed by 3‐hours reoxygenation. Dexmedetomidine administration at the beginning of reperfusion or reoxygenation attenuated I/R‐induced myocardial injury or H/R‐induced cell death, alleviated mitochondrial dysfunction, reduced the number of apoptotic cardiomyocytes, inhibited the activation of HIF‐1α and modulated the expressions of apoptosis‐related proteins including BCL‐2, BAX, BNIP3, cleaved caspase‐3 and cleaved PARP. Conversely, the HIF‐1α prolyl hydroxylase‐2 inhibitor IOX2 partly blocked DEX‐mediated cardioprotection both in vivo and in vitro. Mechanistically, DEX down‐regulated HIF‐1α expression at the post‐transcriptional level and inhibited the transcriptional activation of the target gene BNIP3. Post‐treatment with DEX protects against cardiac I/R injury in vivo and H/R injury in vitro. These effects are, at least in part, mediated via the inhibition of cell apoptosis by targeting HIF‐1α signalling.

Background Pancreatic cancer has been a threateningly lethal malignant tumor worldwide. Despite the promising survival improvement in other cancer types attributing to the fast development of molecular precise medicine, the current treatment situation of pancreatic cancer is still woefully challenging since its limited response to neither traditional radiotherapy and chemotherapy nor emerging immunotherapy. The study is to explore potential responsible genes during the development of pancreatic cancer, thus identifying promising gene indicators and probable drug targets. Methods Different bioinformatic analysis were used to interpret the genetic events in pancreatic cancer development. Firstly, based on multiple cDNA microarray profiles from Gene Expression Omnibus (GEO) database, the genes with differently mRNA expression in cancer comparing to normal pancreatic tissues were identified, followed by being grouped based on the difference level. Then, GO and KEGG were performed to separately interpret the multiple groups of genes, and further Kaplan–Meier survival and Cox Regression analysis assisted us to scale down the candidate genes and select the potential key genes. Further, the basic physicochemical properties, the association with immune cells infiltration, mutation or other types variations besides expression gap in pancreatic cancer comparing to normal tissues of the selected key genes were analyzed. Moreover, the aberrant changed expression of key genes was validated by immunohistochemistry (IHC) experiment using local hospital tissue microarray samples and the clinical significance was explored based on TCGA clinical data. Results Firstly, a total of 22,491 genes were identified to express differently in cancer comparing to normal pancreatic tissues based on 5 cDNA expression profiles, and the difference of 487/22491 genes was over eightfold, and 55/487 genes were shared in multi profiles. Moreover, after genes interpretation which showed the > eightfold genes were mainly related to extracellular matrix structural constituent regulation, Kaplan–Meier survival and Cox-regression analysis were performed continually, and the result indicated that of the 55 extracellular locating genes, GPRC5A and IMUP were the only two independent prognostic indicators of pancreatic cancer. Further, detailed information of IMUP and GPRC5A were analyzed including their physicochemical properties, their expression and variation ratio and their association with immune cells infiltration in cancer, as well as the probable signaling pathways of genes regulation on pancreatic cancer development. Lastly, local IHC experiment performed on PAAD tissue array which was produced with 62 local hospital patients samples confirmed that GPRC5A and IMUP were abnormally up-regulated in pancreatic cancer, which directly associated with worse patients both overall (OS) and recurrence free survival (RFS). Conclusions Using multiple bioinformatic analysis as well as local hospital samples validation, we revealed that GPRC5A and IMUP expression were abnormally up-regulated in pancreatic cancer which associated statistical significantly with patients survival, and the genes’ biological features and clinical significance were also explored. However, more detailed experiments and clinical trials are obligatory to support their further potential drug-target role in clinical medical treatment.

Background Most stroke survivors have sustained upper limb impairment in their distal joints. An electromyography (EMG)-driven wrist/hand exoneuromusculoskeleton (WH-ENMS) was developed previously. The present study investigated the feasibility of a home-based self-help telerehabilitation program assisted by the aforementioned EMG-driven WH-ENMS and its rehabilitation effects after stroke. Methods Persons with chronic stroke (n = 11) were recruited in a single-group trial. The training progress, including the training frequency and duration, was telemonitored. The clinical outcomes were evaluated using the Fugl–Meyer Assessment (FMA), Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), Motor Functional Independence Measure (FIM), and Modified Ashworth Scale (MAS). Improvement in muscle coordination was investigated in terms of the EMG activation level and the Co-contraction Index (CI) of the target muscles, including the abductor pollicis brevis (APB), flexor carpi radialis-flexor digitorum (FCR-FD), extensor carpi ulnaris-extensor digitorum (ECU-ED), biceps brachii (BIC), and triceps brachii (TRI). The movement smoothness and compensatory trunk movement were evaluated in terms of the following two kinematic parameters: number of movement units (NMUs) and maximal trunk displacement (MTD). The above evaluations were conducted before and after the training. Results All of the participants completed the home-based program with an intensity of 63.0 ± 1.90 (mean ± SD) min/session and 3.73 ± 0.75 (mean ± SD) sessions/week. After the training, motor improvements in the entire upper limb were found, as indicated by the significant improvements (P Conclusions The results suggested that the home-based self-help telerehabilitation program assisted by EMG-driven WH-ENMS is feasible and effective for improving the motor function of the paretic upper limb after stroke. Trial registration ClinicalTrials.gov. NCT03752775; Date of registration: November 20, 2018.

Background Dental injury is an underrecognized preventable complication during endoscopy. An audit of same-day procedure cancellation in our endoscopy center showed that 43% of cases are related to tooth safety concerns. A review of the literature showed that dental injury was under-reported in endoscopy related journals but an important issue in anaesthesia. Dental injury in anaesthesia is variably estimated to occur at a rate of approximately one in 1,000 to 4,500. It represents up to half of all anaesthetic claims. We reviewed the preventive measures and management strategy of dental injury. Methods We have reviewed the available literature and worked with a dental expert to suggest a few steps to improve tooth safety during endoscopy: Results Key steps in preventive measures: 1) Pre-endoscopic tooth screening: Optimal pre-endoscopic assessment should include a comprehensive dental assessment, documentation and explanation of individualized risk involved. 2) Identification of risk factors: Evidence of periodontal disease and its infective complications, pre-existing dental pathology such as missing or loose teeth, and dental restorations. 3) Comprehensive documentation of pre-existing dental defects prior to endoscopy should be done. Key steps in dental injury management: 1) Early involvement of dentist: If a dental injury occurs or a missing tooth is found during endoscopy, a dentist should be called to do an on-table consult. 2) Tooth retrieval whenever possible: If the dentist is unavailable or delayed, the missing tooth should be localised and retrieved. Upon retrieval of the tooth or tooth fragments, the dental officer on-call should be consulted for specific management. 3) Radiographic assistance: If localisation is not possible, a chest X-ray should be done, with the consultation of Thoracic Surgery. Conclusions We encourage these simple measures to be implemented in the clinic and endoscopy center to prevent dental injury during endoscopy.

Celecoxib (CXB) is the only clinical cyclooxygenase-2 (COX-2) inhibitor. Oral administration of CXB in experimental diabetic mice effectively relieved the symptoms of diabetic neuropathy (DN); however, the molecular mechanism remains unclear. The present study aimed to investigate the potential molecular mechanisms of CXB in the treatment of DN. An in vitro cellular model of DN was produced by stimulating dorsal root ganglion (DRG) neurons with high glucose. Cell viability and apoptosis were assessed by Cell Counting Kit-8 assays and flow cytometry, respectively. Reactive oxygen species (ROS) kits, ELISA kits and western blotting were used to determine oxidative cellular damage. The expression level of microRNA (miR)-155 was analyzed by reverse transcription-quantitative PCR. The starBase database and dual-luciferase assays were performed to predict and determine the interaction between miR-155 and COX-2. Protein expression of neurotrophic factors, oxidative stress-related proteins and COX-2 were analyzed by western blotting. Incubation with high glucose led to a decrease in DRG neuron cell viability, facilitated apoptosis, downregulated NGF and BDNF expression, increased ROS and MDA generation and decreased SOD activity. Treatment with CXB significantly protected DRG neurons against high glucose-evoked damage. CXB promoted the expression of miR-155 and COX-2 was revealed to be a direct target of miR-155. Inhibition of COX-2 enhanced the protective effect of CXB on DRG neurons and that treatment with an miR-155 inhibitor partially rescued this effect. The present study demonstrated the involvement of the miR-155/COX-2 axis in the protective effect of CXB against high glucose-induced DN.

Vowel-intrinsic fundamental frequency (IF0), the phenomenon that high vowels tend to have a higher fundamental frequency (f0) than low vowels, has been studied for over a century, but its causal mechanism is still controversial. The most commonly accepted “tongue-pull” hypothesis successfully explains the IF0 difference between high and low vowels but fails to account for gradient IF0 differences among low vowels. Moreover, previous studies that investigated the articulatory correlates of IF0 showed inconsistent results and did not appropriately distinguish between the tongue and the jaw. The current study used articulatory and acoustic data from two large corpora of American English (44 speakers in total) to examine the separate contributions of tongue and jaw height on IF0. Using data subsetting and stepwise linear regression, the results showed that both the jaw and tongue heights were positively correlated with vowel f0, but the contribution of the jaw to IF0 was greater than that of the tongue. These results support a dual mechanism hypothesis in which the tongue-pull mechanism contributes to raising f0 in non-low vowels while a secondary “jaw-push” mechanism plays a more important role in lowering f0 for non-high vowels.

Background Clear cell renal cell carcinoma (ccRCC) has been the commonest renal cell carcinoma (RCC). Although the disease classification, diagnosis and targeted therapy of RCC has been increasingly evolving attributing to the rapid development of current molecular pathology, the current clinical treatment situation is still challenging considering the comprehensive and progressively developing nature of malignant cancer. The study is to identify more potential responsible genes during the development of ccRCC using bioinformatic analysis, thus aiding more precise interpretation of the disease Methods Firstly, different cDNA expression profiles from Gene Expression Omnibus (GEO) online database were used to screen the abnormal differently expressed genes (DEGs) between ccRCC and normal renal tissues. Then, based on the protein–protein interaction network (PPI) of all DEGs, the module analysis was performed to scale down the potential genes, and further survival analysis assisted our proceeding to the next step for selecting a credible key gene. Thirdly, immunohistochemistry (IHC) and quantitative real-time PCR (QPCR) were conducted to validate the expression change of the key gene in ccRCC comparing to normal tissues, meanwhile the prognostic value was verified using TCGA clinical data. Lastly, the potential biological function of the gene and signaling mechanism of gene regulating ccRCC development was preliminary explored. Results Four cDNA expression profiles were picked from GEO database based on the number of containing sample cases, and a total of 192 DEGs, including 39 up-regulated and 153 down-regulated genes were shared in four profiles. Based on the DEGs PPI network, four function modules were identified highlighting a FGF1 gene involving PI3K-AKT signaling pathway which was shared in 3/4 modules. Further, both the IHC performed with ccRCC tissue microarray which contained 104 local samples and QPCR conducted using 30 different samples confirmed that FGF1 was aberrant lost in ccRCC. And Kaplan–Meier overall survival analysis revealed that FGF1 gene loss was related to worse ccRCC patients survival. Lastly, the pathological clinical features of FGF1 gene and the probable biological functions and signaling pathways it involved were analyzed using TCGA clinical data. Conclusions Using bioinformatic analysis, we revealed that FGF1 expression was aberrant lost in ccRCC which statistical significantly correlated with patients overall survival, and the gene’s clinical features and potential biological functions were also explored. However, more detailed experiments and clinical trials are needed to support its potential drug-target role in clinical medical use.

Background Lung cancer has been a common malignant tumor with a leading cause of morbidity and mortality, current molecular targets are woefully lacking comparing to the highly progressive cancer. The study is designed to identify new prognostic predictors and potential gene targets based on bioinformatic analysis of Gene Expression Omnibus (GEO) database. Methods Four cDNA expression profiles GSE19188, GSE101929, GSE18842 and GSE33532 were chosen from GEO database to analyze the differently expressed genes (DEGs) between non-small cell lung cancer (NSCLC) and normal lung tissues. After the DEGs functions were analyzed, the protein–protein interaction network (PPI) of DEGs were constructed, and the core gene in the network which has high connectivity degree with other genes was identified. We analyzed the association of the gene with the development of NSCLC as well as its prognosis. Lastly we explored the conceivable signaling mechanism of the gene regulation during the development of NSCLC. Results A total of 92 up regulated and 214 down regulated DEGs were shared in four cDNA expression profiles. Based on their PPI network, TOP2A was connected with most of other genes and was selected for further analysis. Kaplan–Meier overall survival analysis (OS) revealed that TOP2A was associated with worse NSCLC patients survival. And both GEPIA analysis and immunohistochemistry experiment (IHC) confirmed that TOP2A was aberrant gain of expression in cancer comparing to normal tissues. The clinical significance of TOP2A and probable signaling pathways it involved in were further explored, and a positive correlation between TOP2A and TPX2 expression was found in lung cancer tissues. Conclusion Using bioinformatic analysis, we revealed that TOP2A could be adopted as a prognostic indicator of NSCLC and it potentially regulate cancer development through co-work with TPX2. However, more detailed experiments are needed to clarify its drug target role in clinical medical use.

Swelling, mechanical strength, flexibility, and toughness are important parameters in hydrogel preparation for application in the human body. Herein, composite hydrogels were prepared using a mix of Konjac glucomannan (KGM), sodium alginate (SA), and polyvinyl alcohol (PVA) cross-linked by calcium hydroxide. The PVA/KGM/SA composite hydrogel showed a suitable swelling ratio and rate, as well as elasticity and flexibility. In addition, the elongation at break was 660.3%, with a breaking strength of 87.25 kPa and a compression modulus of 1.660 MPa. Rheological studies showed that the composite hydrogel was composed of a multiply cross-linked network involving chemical and physical interactions, thereby affecting the elasticity and flexibility of the gel. Interestingly, the composite gel network was reformed when the temperature decreased. In rabbit models of dry eye, the hydrogel effectively maintained the normal tear meniscus height and increased the low tear meniscus area. The results therefore showed that the PVA/KGM/SA gels not only provide a simple, effective, and safe method for the preparation of hydrogels, but also have potential applications in the treatment of dry eye syndrome.

PURPOSE The purpose of this study was to investigate the effect of 21-gene recurrence score (RS) on predicting prognosis and chemotherapy decision in node micrometastases (N1mi) breast invasive ductal carcinoma (IDC). Methods Patients with stage T1-2N1mi and estrogen receptor-positive IDC diagnosed between 2004 and 2015 were included. The associations of 21-gene RS with breast cancer-specific survival (BCSS), chemotherapy decision, and benefit of chemotherapy were analyzed. RESULTS We identified 4,758 patients including 1,403 patients (29.5%) treated with adjuvant chemotherapy. In the traditional RS cutoffs, 2,831 (59.5%), 1,634 (34.3%), and 293 (6.2%) patients were in the low-, intermediate-, and high-risk RS groups, respectively. In 3,853 patients with human epidermal growth factor receptor-2 (HER2) status available, most patients were HER2-negative disease (98.3%). A higher RS was independently related to chemotherapy receipt, and 14.0%, 47.7%, and 77.8% of patients in the low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. The multivariate analysis indicated that a higher RS was related to worse BCSS (p < 0.001). The 5-year BCSS rates were 99.3%, 97.4%, and 91.9% in patients with low-, intermediate-, and high-risk RS groups, respectively (p < 0.001). However, chemotherapy receipt did not correlate with better BCSS in low-, intermediate-, or high-risk RS groups. There were similar trends using Trial Assigning Individualized Options for Treatment RS cutoffs. CONCLUSION The 21-gene RS does predict outcome and impact on chemotherapy decision of N1mi breast IDC. Large cohort and long-term outcomes studies are needed to identify the effects of chemotherapy in N1mi patients by different 21-gene RS groups.

Adenosine monophosphate-activated protein kinase (AMPK) plays a key role in cellular energy homeostasis and cell proliferation. MicroRNAs (miRNAs) function as posttranscriptional regulators of gene expression in biological processes. It is unclear to whether miRNAs are involved in AMPK-regulated Sertoli cell (SC) proliferation. To further understand the regulation of miRNAs in the immature boar SC proliferation, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) was added to activate AMPK. By an Illumina small RNA deep sequencing, we obtained sequences and relative expression levels of 272 known mature miRNAs, among which 9 miRNAs were significantly upregulated whereas 16 miRNAs were downregulated following the AICAR treatment. The results identified 38 conserved miRNAs, with 8 significantly downregulated miRNAs whereas no upregulated miRNAs. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses suggested that miR-1285 was involved in many activities and pathways associated with cell proliferation via targeting on AMPKα2. We validated that AICAR significantly downregulated miR-1285 level in SCs. Transfection of miR-1285 mimic increased the SC viability and cell cycle progression but reduced AMPKα2 mRNA and protein levels, indicating that miR-1285 is involved in the immature boar SC proliferation via downregulating AMPKα2 expression.

The application of electric field stimulation (EFS) can reduce the cation influx after spinal cord injury. However, regenerated cation influx and reestablished injury potential are observed after EFS. Polyethylene glycol (PEG) is popular as an effective cell membrane fusion agent. This study aims to determine the effects of the combination therapy of EFS and PEG in the ex vivo spinal cord after compression. The ex vivo spinal cords of female rats with compression injury were incubated in a double sucrose gap recording chamber (DSGRC) and randomly divided into the following four groups: (1) compression group: compression only, (2) EFS group: EFS for 15 min, (3) PEG group: PEG treatment for 4 min, and (4) EFS + PEG group: EFS for 15 min and PEG treatment for 4 min. The hematoxylin-eosin staining was performed to measure the necrotic area of the spinal cords. The gap potential was detected, and the area under the curve of the gap potential was calculated. The intracellular cation concentration, membrane permeability, and compound action potential were measured and quantified. Results revealed no significant difference in the necrotic areas among different groups, and the compression model of the ex vivo spinal cord in the DSGRC had high consistency and stability. The combination therapy could attenuate cation inflow, promote cell membrane restoration, and promote the functional recovery of the spinal cord conduction after compression in ex vivo spinal cords.

Background/Aim: The purpose of this study was to provide preliminary data concerning the effect of clear speech (CS) on Cantonese alaryngeal speakers’ intelligibility. Methods: Voice recordings of 11 sentences randomly selected from the Cantonese Sentence Intelligibility Test (CSIT) were obtained from 31 alaryngeal speakers (9 electrolarynx [EL] users, 10 esophageal speakers and 12 tracheoesophageal [TE] speakers) in habitual speech (HS) and CS. Two naïve listeners orthographically transcribed a total of 1,364 sentences. Results: Significant effects of speaking condition on speaking rate and CSIT scores were observed, but no significant effect of alaryngeal communication methods was noted. CS was significantly slower than HS by 0.78 syllables/s. Esophageal speakers demonstrated the slowest speech rate when using CS, while EL users demonstrated the largest decrease in speaking rate when using CS compared to HS. TE speakers had the highest CSIT scores in HS (listener 1 = 81.4%; listener 2 = 81.3%), and esophageal speakers had the highest CSIT scores in CS (listener 1 = 87.5%; listener 2 = 89.7%). EL users experienced the largest increase in intelligibility while using CS compared to HS (9.1%) followed by esophageal speakers (8.9%) and TE speakers (1.4%). Conclusion: Preliminary data indicate that CS may significantly affect Cantonese alaryngeal speakers’ speaking rate and intelligibility. However, intelligibility appeared to vary considerably across speakers. Further research involving larger, heterogeneous groups of speakers and listeners alongside longer and more refined CS training protocols should be conducted to confirm that CS can improve Cantonese alaryngeal speakers’ intelligibility.

Skin wound is a very common type of injury and the healing process greatly affects the life quality of individuals. Ozone has been shown beneficial to wound healing with unclear mechanisms. Here, we tested the effect of ozone oil (OZ) on wound healing and investigated the underlying mechanisms. Mouse skin wound model and Masson staining were used to evaluate the effect of OZ on wound healing. Primary fibroblast culture was employed to assess the functions of OZ, miR-21-5p, and RASA1. QRT-PCR and western blot were used to determine expression levels of miR-21-5p, RASA1, α-SMA, and collagen I. CCK-8 assay and scratch wound healing assay were used to measure viability and migration of fibroblasts. Dual luciferase activity assay was performed to validate miR-21-5p/RASA1 interaction. OZ accelerated wound healing in mice and promoted proliferation and migration abilities of fibroblasts. miR-21-5p was increased while RASA1 was reduced during the wound healing and OZ treatment augmented those changes, as well as increased levels of α-SMA and collagen I. Knockdown of miR-21-5p suppressed those effects of OZ on fibroblasts. Furthermore, miR-21-5p directly targeted RASA1 mRNA and negatively regulated its expression. Overexpression of RASA1 inhibited fibroblast proliferation and migration as well as diminished α-SMA and collagen I protein expression. Additionally, RASA1 overexpression blocked the promotion of miR-21-5p overexpression on fibroblast viability and migration. In vivo, miR-21-5p facilitated wound healing while overexpression of RASA1 reversed the effect. OZ promoted wound healing by enhancing miR-21-5p-mediated RASA1 inhibition to increase fibroblast proliferation and migration.

This article presents a novel electromyography (EMG)-driven exoneuromusculoskeleton that integrates the neuromuscular electrical stimulation (NMES), soft pneumatic muscle, and exoskeleton techniques, for self-help upper limb training after stroke. The developed system can assist the elbow, wrist, and fingers to perform sequential arm reaching and withdrawing tasks under voluntary effort control through EMG, with a lightweight, compact, and low-power requirement design. The pressure/torque transmission properties of the designed musculoskeletons were quantified, and the assistive capability of the developed system was evaluated on patients with chronic stroke (

Purpose The purpose of this study was to report the variability of electrolarynx (EL) users' speech intelligibility in quiet and in multitalker babble. Method Ten EL users (five Servox® Digital, five TruTone™) who were at least 2 years postlaryngectomy provided recordings of five sentences from the 1965 Revised List of Phonetically Balanced Sentences. Recordings were judged by two groups of naïve listeners in quiet and in the presence of multitalker babble. Fifteen listeners orthographically transcribed a total of 750 sentences containing 3,750 key words in quiet, and another 15 listeners orthographically transcribed the same sentences mixed with multitalker babble. Results Significant differences in speech intelligibility were observed between listening conditions; 17.9% more key words were correctly identified in quiet compared to multitalker babble. Significant differences in fundamental frequency (F 0 ) standard deviation and range but not speech intelligibility were observed between EL device types. A positive correlation of moderate significance was observed between F 0 standard deviation and intelligibility for TruTone users in multitalker babble. Conclusions Findings suggest that listeners are able to identify a significantly higher percentage of EL users' speech in quiet compared to multitalker babble, but a large variability in EL users' speech intelligibility exists. Continued investigation involving a larger number of EL users is necessary to confirm this study's findings. Future research should explore the relationships among F 0 measures, speaker characteristics (e.g., rate of speech, articulatory precision), and speech intelligibility, in addition to improving alaryngeal rehabilitation training protocols for EL users.

Background Lung cancer has been the leading cause of tumor related death, and 80% ~ 85% of it is non-small cell lung cancer (NSCLC). Even with the rising molecular targeted therapies, for example EGFR, ROS1 and ALK, the treatment is still challenging. The study is to identify credible responsible genes during the development of NSCLC using bioinformatic analysis, developing new prognostic biomarkers and potential gene targets to the disease. Methods Firstly, three genes expression profiles GSE44077, GSE18842 and GSE33532 were picked from Gene Expression Omnibus (GEO) to analyze the genes with different expression level (GDEs) between NSCLC and normal lung samples, and the cellular location, molecular function and the biology pathways the GDEs enriched in were analyzed. Then, gene function modules of GDEs were explored based on the protein-protein interaction network (PPI), and the top module which contains most genes was identified, followed by containing genes annotation and survival analysis. Moreover, multivariate cox regression analysis was performed in addition to the Kaplan meier survival to narrow down the key genes scale. Further, the clinical pathological features of the picked key genes were explored using TCGA data. Results Three GEO profiles shared a total of 664 GDEs, including 232 up-regulated and 432 down-regulated genes. Based on the GDEs PPI network, the top function module containing a total of 69 genes was identified, and 31 of 69 genes were mitotic cell cycle regulation related. And survival analysis of the 31 genes revealed that 17/31 genes statistical significantly related to NSCLC overall survival, including 4 spindle assembly checkpoints, namely NDC80, BUB1B, MAD2L1 and AURKA. Further, multivariate cox regression analysis identified NDC80 and MAD2L1 as independent prognostic indicators in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) respectively. Interestingly, pearson correlation analysis indicated strong connection between the four genes NDC80, BUB1B, MAD2L1 and AURKA, and their clinical pathological features were addressed. Conclusions Using bioinformatic analysis of GEO combined with TCGA data, we revealed two independent prognostic indicators in LUAD and LUSC respectively and analyzed their clinical features. However, more detailed experiments and clinical trials are needed to verify their drug targets role in clinical medical use.

Background: Early extubation can reduce pulmonary complications in children undergoing cardiac surgery. The aim of this study is to evaluate the effects of sugammadex for postoperative respiratory management in children with congenital heart disease. Methods: Sixty children with congenital heart disease undergoing elective cardiac surgery were divided into group S and group C (30 children in each group). When post tetanic twitches count (PTC) = 1-2 and train-of-four (TOF) = 0, the children in group S received sugammadex4 mg/kg for reversal of neuromuscular block at the end of surgery, and the children in group C received the same volume of normal saline. The recovery time to TOF of 0.9, the mechanical ventilation and extubation times were recorded. On the other side, the hemodynamic parameters before and 5 min after administration, and side effects were also recorded. The levels of C-reactive protein (CRP) and procalcitonin (PCT) before and 24 h after surgery were measured. Results: The recovery time to TOF of 0.9 and extubation time were significantly shorter in the group S than in the group C (4.2 ± 1.4 vs 108.2 ± 26.7 min, 66.3 ± 6.5 vs 171.6 ± 23.1 min, respectively, P 0.05) with respect to side effects. Conclusion: Sugammadex is rapid and effective in reversing rocuronium-induced neuromuscular block, and significantly reduces the extubation time and the release of postoperative CRP and PCT in children with congenital heart diseases.

Aims Patients with metabolic syndrome (MetS) are known to be at increased risk of postoperative complications, but it is unclear whether MetS is also associated with complications after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Here, we perform a systematic review and meta-analysis linking MetS to postoperative complications in THA and TKA. Methods The PubMed, OVID, and ScienceDirect databases were comprehensively searched and studies were selected and analyzed according to the guidelines of the Meta-analysis of Observational Studies in Epidemiology (MOOSE). We assessed the methodological quality of each study using the Newcastle-Ottawa Scale (NOS), and we evaluated the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Data were extracted and meta-analyzed or qualitatively synthesized for several outcomes. Results Ten cohort studies involving 1,352,685 patients were included. Qualitative analysis suggested that MetS was associated with a higher incidence of cardiovascular events, and meta-analysis showed that MetS increased the risk of all-cause complications (risk ratio (RR) 1.55, 95% confidence interval (CI) 1.28 to 1.89), surgical site infection (SSI; RR 2.99, 95% CI 1.30 to 6.90), urinary tract infection (UTI; RR 2.58, 95% CI 1.03 to 6.43), and 30-day readmission (RR 1.45, 95% CI 1.33 to 1.59). There was insufficient evidence for assessing an association between MetS and venous thromboembolism events, pulmonary or gastrointestinal complications, or mortality. Conclusion Patients with MetS undergoing THA and TKA are at increased risk of all-cause complications, cardiovascular complications, SSI, UTI, and 30-day readmission. Surgeons should be aware of the increased risk of these complications in MetS, and presurgical protocols for these complications should give special consideration to MetS patients. Cite this article: Bone Joint Res. 2020;9(3):120–129.

The disorder of bile acid metabolism is a common feature during pregnancy, which leads to adverse birth outcomes and maternal damage effects. However, the cause and therapy about the disorder of bile acid metabolism are still poor. Microbial infection often occurs in pregnant women, which can induce the disorder of bile acid metabolism in adult mice. Here, this study observed the acute effect of lipopolysaccharide (LPS) on maternal bile acid of pregnant mice at gestational day 17 and the protective effect of obeticholic acid (OCA) pretreatment, a potent agonist of bile acid receptor farnesoid X receptor (FXR). The results showed LPS significantly increased the level of maternal serum and disordered bile acids components of maternal serum and liver, which were ameliorated by OCA pretreatment with obviously reducing the contents of CA, TCA, DCA, TCDCA, CDCA, GCA and TDCA in maternal serum and DCA, TCA, TDCA, TUDCA, CDCA and TCDCA in maternal liver. Furthermore, we investigated the effects of OCA on LPS-disrupted bile acid metabolism in maternal liver. LPS disrupted maternal bile acid profile by decreasing transport and metabolism with hepatic tight junctions of bile acid in pregnant mice. OCA obviously increased the protein level of nuclear FXR and regulated its target genes involving in the metabolism of bile acid, which was characterized by the lower expression of bile acid synthase CYP7A1, the higher expression of CYP3A and the higher mRNA level of transporter Mdr1a/b. This study provided the evidences that LPS disrupted bile acid metabolism in the late stage of pregnant mice and OCA pretreatment played the protective role on it by activating FXR.

Current rehabilitation treatments for post-stroke upper limb motor deficits are experiencing a shortage of professional manpower to provide adequate and precise physical practice. Rehabilitation robots and neuromuscular electrical stimulation have been adopted as efficient supplements to manual therapy. In this chapter, a novel NMES-robotic hybrid training system adopting two upper limb supportive schemes (i.e., support to the finger–hand and support to the wrist–elbow) with different mechanical structures will be introduced with three clinical trials. The training effectiveness of this system in both subacute and chronic stroke was evaluated through trials based on both the clinical assessments (i.e., the Fugl-Meyer Assessment the Modified Ashworth Scale the Action Research Arm Test and the Functional Independence Measurement ) and cross-session electromyography (EMG) parameters (i.e., electromyography activation level and the cocontraction index). Furthermore, the training effects by two supportive schemes are compared to identify the optimized choice.

The purpose of the present study was to evaluate the efficacy of extraluminal use of the bronchial blocker (BB) for one-lung ventilation (OLV) in infants undergoing thoracoscopic surgery.This was a prospective, randomized, controlled clinical study.University hospital.The study comprised 60 infants undergoing thoracoscopic surgery.The study included 2 groups. A BB was placed extraluminally for OLV in group A, and a single-lumen endobronchial tube was inserted into the desired mainstem bronchus for OLV in group C.The placement time (4.0 ± 0.6 min v 6.3 ± 4.1 min; p = 0.04) and the number of repositions (2 v 11; p = 0.005) were less in group A. There were significant differences in the heart rate and blood pressure after insertion between the 2 groups (p0.05). The tidal volumes and end-tidal pressure of carbon dioxide values 10 minutes after the initiation of OLV were similar between the 2 groups (p0.05). The incidence of intraoperative hypoxemia was reduced in group A compared with group C (0% v 20%; p = 0.024). No postoperative adverse events were observed in either group.Extraluminal use of the BB may provide a solution for a rapid placement and excellent quality of lung isolation, and it may reduce the incidence of intraoperative hypoxemia in infants without increasing the incidence of hoarseness.

Patterns of relative timing between consonants and vowels appear to be conditioned in part by phonological structure, such as syllables, a finding captured naturally by the two-level feedforward model of Articulatory Phonology (AP). In AP, phonological form – gestures and the coordination relations between them – receive an invariant description at the inter-gestural level. The inter-articulator level actuates gestures, receiving activation from the inter-gestural level and resolving competing demands on articulators. Within this architecture, the inter-gestural level is blind to the location of articulators in space. A key prediction is that intergestural timing is stable across variation in the spatial position of articulators. We tested this prediction by conducting an Electromagnetic Articulography (EMA) study of Mandarin speakers producing CV monosyllables, consisting of labial consonants and back vowels in isolation. Across observed variation in the spatial position of the tongue body before each syllable, we investigated whether inter-gestural timing between the lips, for the consonant, and the tongue body, for the vowel, remained stable, as is predicted by feedforward control, or whether timing varied with the spatial position of the tongue at the onset of movement. Results indicated a correlation between the initial position of the tongue gesture for the vowel and C-V timing, indicating that inter-gestural timing is sensitive to the position of the articulators, possibly relying on somatosensory feedback. Implications of these results and possible accounts within the Articulatory Phonology framework are discussed.

In 2015, the Chinese pharmacologist, Tu Youyou, was awarded the Nobel Prize for Physiology or Medicine for the discovery of artemisinin. Traditional Chinese medicine (TCM) was the source of inspiration for Tu's discovery and provides an opportunity for the world to know more about TCM as a source of medical knowledge and practice. In this article, the value of TCM is evaluated from an ethical perspective. The characteristics of ‘jian, bian, yan, lian’ are explored in the way they promote accessibility and economic efficiency for TCM. The article also examines how the increased use and prevalence of TCM reflects the scientific, cultural, and ethical values of TCM and their increasing attraction in meeting major challenges to medicine and health systems currently and in the future. The article discusses safety issues within TCM, which is a controversial area, and also comments on some shortcomings and challenges which pose difficulties for more widespread and greater uptake of TCM‐derived clinical or therapeutic interventions. The article concludes that TCM is generally safe if it is used according to TCM theory and where such applications are cognizant of the strengths and weaknesses of TCM. TCM has important bioethical values which may inform potential measures for meeting challenges facing global health care systems and the article argues that it can have an increasing role in improving human health.

The leafminer Liriomyza trifolii is an important insect pest of ornamental and vegetable crops worldwide. Temperature is a critical environmental factor that impacts both the distribution and interspecific competition of Liriomyza spp. In this study, we compared the transcriptomes of L. trifolii exposed to ambient (25 °C), hot (43 °C), and cold (-7 °C) temperatures. RNA-seq revealed 100,041 assembled unigenes, and 50,546 of these were annotated in L. trifolii transcriptome libraries. A total of 207 and 2904 differentially expressed genes (DEGs) were identified in response to hot and cold stress, respectively. Functional classification indicated that “cellular process”, “single organism processes” and “metabolic processes” pathways were significantly enriched, along with “binding activity” and “catalytic activity”. With respect to clusters of orthologous genes (COG) classification, DEGs were assigned to “post-translational modification, protein turnover, chaperones”, “carbohydrate transport and metabolism” and “lipid transport and metabolism” categories. Subsequent annotation and enrichment analyses indicated that genes encoding heat shock proteins (HSPs) and cuticular proteins were significantly up-regulated during heat and cold stress, respectively. This study expands our knowledge of gene expression in L. trifolii during temperature stress and provides a basis for further studies aimed at understanding the mechanism of thermotolerance in this important invasive leafminer fly.

Lactate produced by Sertoli cells plays an important role in spermatogenesis, and heat stress induces lactate production in immature boar Sertoli cells. Extracellular signaling regulated kinase 1 and 2 (ERK1/2) participates in heat stress response. However, the effect of ERK1/2 on heat stress-induced lactate production is unclear. In the present study, Sertoli cells were isolated from immature boar testis and cultured at 32 °C. Heat stress was induced in a 43 °C incubator for 30 min. Proteins and RNAs were detected by western blotting and RT-PCR, respectively. Lactate production and lactate dehydrogenase (LDH) activity were detected using commercial kits. Heat stress promoted ERK1/2 phosphorylation, showing a reducing trend with increasing recovery time. In addition, heat stress increased heat shock protein 70 (HSP70), glucose transporter 3 (GLUT3), and lactate dehydrogenase A (LDHA) expressions, enhanced LDH activity and lactate production at 2-h post-heat stress. Pretreatment with U0126 (1 × 10(−6) mol/L), a highly selective inhibitor of ERK1/2 phosphorylation, reduced HSP70, GLUT3, and LDHA expressions and decreased LDH activity and lactate production. Meanwhile, ERK2 siRNA1 reduced the mRNA level of ERK2 and weakened ERK1/2 phosphorylation. Additionally, ERK2 siRNA1 reduced HSP70, GLUT3, and LHDA expressions decreased LDH activity and lactate production. Furthermore, HSP70 siRNA3 downregulated GLUT3 and LDHA expressions and decreased LDH activity and lactate production. These results show that activated ERK1/2 increases heat stress-induced lactate production by enhancing HSP70 expression to promote the expressions of molecules related to lactate production (GLUT3 and LDHA). Our study reveals a new insight in reducing the negative effect of heat stress in boars.

Our previous study revealed that early application of electrical field stimulation (EFS) with the anode at the lesion and the cathode distal to the lesion reduced injury potential, inhibited secondary injury and was neuroprotective in the dorsal corticospinal tract after spinal cord injury (SCI). The objective of this study was to further evaluate the effect of EFS on protection of anterior horn motoneurons and their target musculature after SCI and its mechanism. Rats were randomized into three equal groups. The EFS group received EFS for 30 minutes immediately after injury at T10. SCI group rats were only subjected to SCI and sham group rats were only subjected to laminectomy. Luxol fast blue staining demonstrated that spinal cord tissue in the injury center was better protected; cross-sectional area and perimeter of injured tissue were significantly smaller in the EFS group than in the SCI group. Immunofluorescence and transmission electron microscopy showed that the number of spinal cord anterior horn motoneurons was greater and the number of abnormal neurons reduced in the EFS group compared with the SCI group. Wet weight and cross-sectional area of vastus lateralis muscles were smaller in the SCI group to in the sham group. However, EFS improved muscle atrophy and behavioral examination showed that EFS significantly increased the angle in the inclined plane test and Tarlov's motor grading score. The above results confirm that early EFS can effectively impede spinal cord anterior horn motoneuron loss, promote motor function recovery and reduce muscle atrophy in rats after SCI.