Immune checkpoint inhibitors as the second-line treatment for advanced esophageal squamous cell carcinoma: a cost-effectiveness analysis based on network meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have demonstrated superior clinical efficacy in prolonging overall survival (OS) as the second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC), and were recommended by the guidelines. However, it remains uncertain which ICI is the most cost-effective. This study assessed the cost-effectiveness of ICIs as the second-line treatment for ESCC based on the perspective of the Chinese healthcare system. METHODS: A network meta-analysis (NMA) was performed to obtain the Hazard ratios (HRs) for indirect comparisons. A three-state Markov model with a 10-year time horizon was conducted to assess the cost-effectiveness. The state transition probabilities were calculated with Kaplan-Meier (KM) curves data from clinical trial and HRs from the NMA. Utilities and costs were derived from local charges or previously published studies. Univariate and probabilistic sensitivity analyses (PSA) were performed to examine model robustness. The results were assessed based on the total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Five clinical trials (ATTRACTION-3, ESCORT, KEYNOTE-181, ORIENT-2, RATIONALE-302) with a total of 1797 patients were included in the NMA. The NMA showed that both camrelizumab and tislelizumab received relatively high rankings for progression-free survival (PFS) and OS. Compared with sintilimab, treatment with tislelizumab and camrelizumab gained 0.018 and 0.034 additional QALYs, resulting in incremental ICERs of $75,472.65/QALY and $175,681.9/QALY, respectively. Nivolumab and pembrolizumab produced lower QALYs and greater costs, suggesting that both were dominated in comparison to sintilimab. HRs and health state utilities were the most influential parameters in most univariate sensitivity analyses of paired comparisons. PSA results suggested that sintilimab had an 84.4% chance of being the most cost-effective treatment regimen at the WTP threshold of $38,223.34/QALY. In the scenario analysis, sintilimab would no longer be cost-effective, if the price of camrelizumab was assumed to decrease by 64.6% or the price of tislelizumab was assumed to decrease by 16.9%. CONCLUSIONS AND RELEVANCE: Among the five potential competing ICIs, sintilimab was likely to be the most cost-effective regimen as the second-line treatment for locally advanced or metastatic ESCC in China.

Fluoxetine alleviates postoperative cognitive dysfunction by attenuating TLR4/MyD88/NF-κB signaling pathway activation in aged mice.

OBJECTIVE AND DESIGN: Postoperative cognitive dysfunction (POCD) is a common complication following surgery among elderly patients. Emerging evidence demonstrates that neuroinflammation plays a pivotal role in the pathogenesis of POCD. This study tested the hypothesis that fluoxetine can protect against POCD by suppressing hippocampal neuroinflammation through attenuating TLR4/MyD88/NF-κB signaling pathway activation. SUBJECTS: Aged C57BL/6 J male mice (18 months old) were studied. TREATMENT: Aged mice were intraperitoneally injected with fluoxetine (10 mg/kg) or saline for seven days before splenectomy. In addition, aged mice received an intracerebroventricular injection of a TLR4 agonist or saline seven days before splenectomy in the rescue experiment. METHODS: On postoperative days 1, 3, and 7, we assessed hippocampus-dependent memory, microglial activation status, proinflammatory cytokine levels, protein levels related to the TLR4/MyD88/NF-κB signaling pathway, and hippocampal neural apoptosis in our aged mouse model. RESULTS: Splenectomy induced a decline in spatial cognition, paralleled by parameters indicating exacerbation of hippocampal neuroinflammation. Fluoxetine pretreatment partially restored the deteriorated cognitive function, downregulated proinflammatory cytokine levels, restrained microglial activation, alleviated neural apoptosis, and suppressed the increase in TLR4, MyD88, and p-NF-κB p65 in microglia. Intracerebroventricular injection of LPS (1 µg, 0.5 µg/µL) before surgery weakened the effect of fluoxetine. CONCLUSION: Fluoxetine pretreatment suppressed hippocampal neuroinflammation and mitigated POCD by inhibiting microglial TLR4/MyD88/NF-κB pathway activation in aged mice.

Activation of the CD200/CD200R1 axis attenuates neuroinflammation and improves postoperative cognitive dysfunction via the PI3K/Akt/NF-κB signaling pathway in aged mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a neurological complication occurring after anesthesia and surgery. Neuroinflammation plays a critical role in the pathogenesis of POCD, and the activation of the cluster of differentiation 200 (CD200)/CD200R1 axis improves neurological recovery in various neurological disorders by modulating inflammation. The aim of this study was to investigate the impact and underlying mechanism of CD200/CD200R1 axis on POCD in aged mice. METHODS: The model of POCD was established in aged mice. To assess the learning and memory abilities of model mice, the Morris water maze test was implemented. CD200Fc (CD200 fusion protein), CD200R1 Ab (anti-CD200R1 antibody), and 740Y-P (a specific PI3K activator) were used to evaluate the effects of the CD200/CD200R1/PI3K/Akt/NF-κB signaling pathway on hippocampal microglial polarization, neuroinflammation, synaptic activity, and cognition in mice. RESULTS: It was observed that anesthesia/surgery induced cognitive decline in aged mice, increased the levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1 ß and decreased the levels of postsynaptic density protein 95 (PSD-95), synaptophysin (SYN) in the hippocampus. Moreover, CD200Fc and 740Y-P attenuated neuroinflammation and synaptic deficits and reversed cognitive impairment via the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt)/nuclear factor-kappa B (NF-κB) signaling pathway, whereas CD200R1 Ab administration exerted the opposite effects. Our results further show that the CD200/CD200R1 axis modulates M1/M2 polarization in hippocampal microglia via the PI3K/Akt/NF-κB signaling pathway. CONCLUSIONS: Our findings indicate that the activation of the CD200/CD200R1 axis reduces neuroinflammation, synaptic deficits, and cognitive impairment in the hippocampus of aged mice by regulating microglial M1/M2 polarization via the PI3K/Akt/NF-κB signaling pathway.

Enhanced plasmonic photocatalytic performance of C3N4/Cu by the introduction of a reduced graphene oxide interlayer.

Cu nanoparticles (NPs) are low-cost surface plasmonic resonance (SPR) metal nanostructures, and their SPR properties can be used to enhance the photocatalytic hydrogen evolution performance of carbon nitride (C3N4). But their actual performance is usually limited, and one key factor is their poor interfacial quality. In this work, a highly conductive reduced graphene oxide (RGO) interlayer is introduced between protonated C3N4 (PCN) nanosheets and Cu NPs, which can act as an efficient sink for photogenerated electrons from C3N4 and hot electrons from Cu NPs, and simultaneously serve as reaction sites for the hydrogen evolution reaction, and accelerate the charge transport by the formed C-O-C and C-O-Cu bonds. The optimal hydrogen evolution rate of the optimized PCN/RGO/Cu is 1.30 mmol g-1 h-1, which is 6.76, 2.47 and 2.41 times that of PCN, PCN/RGO and PCN/Cu, respectively, and it can further reach up to 13.22 mmol g-1 h-1 by loading moderate Pt NPs. Meanwhile, the introduced RGO can effectively anchor Cu NPs to enhance the stability of the photocatalyst. In addition, due to the broad SPR response of Cu NPs, a near-infrared photocatalytic performance is realized for PCN/RGO/Cu with an apparent quantum efficiency of 0.46% at 765 nm.

Recognition and management of hemorrhaging in combination with emerging enterogenic sepsis during a hepatectomy: a case report.

BACKGROUND: Patients with hemorrhagic shock may develop emerging enterogenic sepsis due to damage to the intestinal mucosal barrier and translocation of intestinal bacteria and endotoxins caused by ischemic injury. Because of the dual effects of anesthesia state and hemorrhagic shock, perioperative emerging enterogenic sepsis is even more rare and insidious. CASE PRESENTATION: We reported a case of 56-year-old man who underwent right hepatectomy for intrahepatic bile duct stones. Severe hemorrhage occurred during the procedure and the hemodynamics neither improved nor worsened after rehydration therapy and vasoactive drug administration. Based on the patient's history and clinical presentation, a possible enterogenic sepsis was considered. After anti-infective treatment and hormone supplementation, the patient's circulation improved significantly and he had an uneventful recovery. CONCLUSION: The possibility of emerging enterogenic sepsis in hemorrhagic shock must always be taken into consideration. Familiarity with the risk factors and pathophysiological alterations of enterogenic sepsis is a prerequisite for early recognition and sound clinical decision making.

A novel bidirectional perfusion-like administered system for NIR-II fluorescence imaging precision diagnosis of bladder cancer.

Intravesical instillation has been considered an efficient route for detecting bladder cancer. However, only a small fraction of administered dose permeates into tumor tissues, and insufficient retention time limits their application. In this work, a novel intravesical bidirectional perfusion-like administered mode was developed to improve diagnostic accuracy of bladder tumor imaging. Specifically, the ultrasmall AuPd-P-FA Nanoprobe exhibit excellent NIR-II FL imaging performance due to electronic structure perturbation. Benefiting from the size advantage for kidney metabolism and FA targeting specificity, AuPd-P-FA could effectively administration to bladder tumor. When AuPd-P-FA reached maximum enrichment at 1 h post-injection, the localized and mild thermal energy produced upon laser irradiation activated a phase transition. This thermo-sensitive characteristic could prolong the retention time in bladder and the fluorescence signal could be clearly observed at 6 h post-injection with high accuracy. This novel intravesical bidirectional perfusion-like administered mode is expected to achieve a non-invasive diagnosis of early bladder cancer.

QR code technology in individual identification training provides an introduction in hands-on forensic DNA genotyping to medical students.

BACKGROUND: Forensic biology is a subject in the field of forensic science that stresses practical teaching and training in laboratory skills. Visualization of deoxyribonucleic acid (DNA) profiles is important in individual identification and is easily performed by well-trained examiners. Therefore, developing a novel training project for obtaining individual DNA profiles can improve the quality of teaching for medical students or trainees. DNA profiles based on quick response (QR) codes can also be applied to practical teaching and operation training for individual identification. METHODS: A novel training project was developed through an experimental course in forensic biology. Blood samples and buccal swabs with oral epithelial cells, as used in the forensic DNA laboratory, were obtained from medical students at Fujian Medical University. DNA was isolated, and a number of short tandem repeat (STR) loci were used as genetic markers to generate DNA profiles. The students converted DNA profiles and individual information into a QR code. The QR code could then be scanned by a mobile phone for consulting and retrieval. Gene identity cards with QR codes were produced and provided to every student. The participation rate and passing rate of students who participated in the novel training project were calculated and compared with those of students in the traditional experimental course, and a chi-square test was carried out by SPSS 23.0 software to evaluate the teaching effectiveness. p < 0.05 indicated significant differences. In addition, a survey was conducted to investigate the likelihood of using of gene identity cards with QR codes in the future. RESULTS: A total of 54 of 91 medical students who studied forensic biology participated in the novel training project in 2021. Only 31 of 78 students who studied forensic biology participated in the traditional experimental course in 2020. The participation rate in the novel training project was 24% higher than that of the traditional experimental course. The participants in the novel training project showed better performance in forensic biological handling techniques. The passing rate of the students in the forensic biology course with the novel training project was approximately 17% higher than that of the students in the former course. The participation rates and passing rates of the two groups were significantly different (χ = 6.452, p = 0.008 and χ = 11.043, p = 0.001). In the novel training project, all participants made 54 gene identity cards with QR codes. Furthermore, in the DNA profiles of four African students who participated, we found two rare alleles that were not discovered in Asians. The survey showed that the use of gene identity cards with QR codes was accepted by most participants, and the likelihood of future utilization was 78%. CONCLUSION: We established a novel training project to promote the learning activities of medical students in experimental forensic biology courses. The participants showed great interest in using gene identity cards with QR codes to store general individual identity information and DNA profiles. They also examined the genetic population differences between different races based on DNA profiles. Hence, the novel training project could be useful for training workshops, forensic experimental courses, and medical big data research.

Research and application of a teaching platform for combined spinal-epidural anesthesia based on virtual reality and haptic feedback technology.

BACKGROUND: Intraspinal anesthesia poses significant teaching challenges and inadequate teaching resources, which ultimately limit students' opportunities for practice. To address this issue, we aimed to develop a virtual platform for combined spinal-epidural anesthesia that merges virtual reality technology with haptic feedback technology, while assessing its educational impact and learning outcomes. METHODS: We utilized MIMICS, 3Ds MAX, and UNITY 3D software to perform 3D reconstruction based on lumbar CT/MRI data from a standard male volunteer. The haptic coefficients were configured on each layer by 20 experienced anesthesiologists in accordance with the Geomagic Touch X force feedback device. A total of 20 anesthesiology interns completed 30 virtual puncture training sessions. Two experienced anesthetists evaluated the efficacy of the platform and the level of mastery achieved using the Global Rating Scale (GRS) and a Checklist score, respectively. Finally, a questionnaire survey was conducted to gather feedback on the virtual platform. RESULTS: After the 10th session, the puncture time stabilized at 2.4 min. As the number of sessions increased, the Global Rating Scale (GRS) score stabilized by the 8th session, and the Checklist scores tended to stabilize by the 10th session. Results from questionnaires indicated that over half of the anesthesiology interns (70%) believed that the platform, which exhibited strong repeatability, improved their anatomical recognition and provided a strong sense of breakthrough in identifying the ligamentum flavum. The majority of them (80%) expressed satisfaction with the virtual platform. CONCLUSIONS: The platform effectively facilitated the acquisition of basic and accurate puncture skills on a virtual patient.

Optimization of a laparoscopic procedure for advanced intrahepatic cholangiocarcinoma based on the concept of "waiting time": a preliminary report.

INTRODUCTION: Clinicians increasingly perform laparoscopic surgery for intrahepatic cholangiocarcinoma (ICC). However, this surgery can be difficult in patients with advanced-stage ICC because of the complicated procedures and difficulty in achieving high-quality results. We compared the effects of a three-step optimized procedure with a traditional procedure for patients with advanced-stage ICC. METHODS: Forty-two patients with advanced-stage ICC who received optimized laparoscopic hemihepatectomy with lymph node dissection (LND, optimized group) and 84 propensity score-matched patients who received traditional laparoscopic hemihepatectomy plus LND (traditional group) were analyzed. Surgical quality, disease-free survival (DFS), and overall survival (OS) were compared. RESULTS: The optimized group had a lower surgical bleeding score (P = 0.038) and a higher surgeon satisfaction score (P = 0.001). Blood loss during hepatectomy was less in the optimized group (190 vs. 295 mL, P < 0.001). The optimized group had more harvested LNs (12.0 vs. 8.0, P < 0.001) and more positive LNs (8.0 vs. 5.0, P < 0.001), and a similar rate of adequate LND (88.1% vs. 77.4%, P = 0.149). The optimized group had longer median DFS (9.0 vs. 7.0 months, P = 0.018) and median OS (15.0 vs. 13.0 months, P = 0.046). In addition, the optimized group also had a shorter total operation time (P = 0.001), shorter liver resection time (P = 0.001), shorter LND time (P < 0.001), shorter hospital stay (P < 0.001), and lower incidence of total morbidities (14.3% vs. 36.9%, P = 0.009). CONCLUSIONS: Our optimization of a three-step laparoscopic procedure for advanced ICC was feasible, improved the quality of liver resection and LND, prolonged survival, and led to better intraoperative and postoperative outcomes.

Optimized hot electron injection from Cu nanoparticles to S-doped C3N4 by the formed S-Cu bonds for an enhanced photocatalytic performance.

Low-cost and high-abundance Cu nanostructures are potential near-infrared (NIR) surface plasmonic resonance (SPR) photosensitizers for carbon nitride (C3N4) photocatalysts, but their low activity and stability need to be improved. In this article, doping S into C3N4 (S-C3N4) creates anchoring sites for photo-deposited Cu nanoparticles (NPs), and the spontaneous construction of S-Cu bonds is realized between S-C3N4 and Cu NPs. The optimal hydrogen evolution rate of 1.64 mmol g-1 h-1 is obtained for S-C3N4-Cu, which is 5.5, 4.6 and 1.7 times that of pure C3N4, S-C3N4 and S-C3N4-Cu, respectively. With further loading of a Pt co-catalyst to confirm the role of Cu NPs and improve the photocatalytic activity of the SCN-Cu, the photocatalytic rate can reach up to 14.34 mmol g-1 h-1. Due to the NIR SPR effect of Cu NPs, the apparent quantum efficiency (AQE) of S-C3N4-Cu at 600 and 765 nm is 2.02% and 0.47%, respectively. The enhanced photocatalytic performance of S-C3N4-Cu compared with C3N4-Cu is mainly due to the introduced S-Cu bonds that improve the injection rate of hot electrons. This solution provides a simple and efficient interface optimization strategy for the construction of efficient NIR-driven photocatalysts.

Comparison of predictive value of risk scores for gastrointestinal bleeding in antiplatelet therapy.

Gastrointestinal bleeding (GIB) is the most common serious bleeding complication of antiplatelet therapy. The bleeding risk score (BRS) of GIB may help to determine the risk of bleeding, and provides a reference for the formulation of antiplatelet therapy regimen in clinical practice, but we found that no specific risk scores are available in East Asian patients. This study analyzed patients who were administered antiplatelet therapy from May 2015 to December 2018 in two medical centers. Patient's baseline data were obtained. We assessed four BRSs (New Score, RIETE Score, Cuschieri Score, de Groot Score) and compared them using the area under the receiver operating characteristic curve (AUC). The 4,052 patients enrolled in this study had an average age of 69.6 ± 10.8 years, and 65.9% of them were male. Among the 4,052 patients included, 171 patients experienced GIB within 6 months of follow-up. In the study population, the AUCs for the New, RIETE, Cuschieri, and de Groot scores were 0.673 (95% confidence interval (CI) 0.616-0.729, P < .001), 0.742 (95% CI 0.690-0.794, P < .001), 0.598 (95% CI 0.537-0.659, P = .002), and 0.875 (95% CI 0.839-0.912, P < .001), respectively. After validation, the de Groot Score has better performance. Among the four scores, the de Groot Score might be more suitable for helping Chinese clinicians to predict the risk of GIB in patients taking antiplatelet drugs, and reduce GIB events.

Dynamic changes of bacteria and screening of potential spoilage markers of lamb in aerobic and vacuum packaging.

Microorganisms proliferate, consume nutrients, and produce many undesired metabolites, which are the main reason for the spoilage of fresh meat. Screening spoilage markers is of great significance for characterizing the freshness of fresh meat. At present, there are few studies on the volatile spoilage markers (VSMs) of lamb and their relationship with bacteria. In this study, the spoilage evolution of lamb was evaluated by multiple indicators. The changes of bacteria and volatile organic compounds (VOCs) in aerobic-packaged (AP) and vacuum-packaged (VP) lamb were measured by 16S next-generation sequencing (NGS) and headspace solid-phase microextraction (HS-SPME)-gas chromatography-mass spectrometry (GC-MS) respectively. The potential VSMs were also screened. Results showed that the shelf life of AP lamb at 4 °C was less than 10 d and VP lamb was less than 28 d. Pseudomonas was the dominant bacteria in AP lamb, while Latilactobacillus and Lactococcus were the dominant bacteria in VP lamb. Several VOCs could be recommended as potential spoilage markers, including 1-octen-3-ol, 1-hexanol, nonanal, methoxy-phenyloxime, 2,3-octanedione, acetoin and 1-pentanol for AP lamb; acetoin, 1-hexanol, 2,3-octanedione, hexanoic acid, 1-octen-3-ol, nonanal, hexanal and 2,3-octanediol for VP lamb. This study can provide information for characterizing and predicting the freshness of fresh lamb.

Discharge readiness after remimazolam versus propofol for colonoscopy: A randomised, double-blind trial.

BACKGROUND: Remimazolam is an ultrashort-acting benzodiazepine that is potentially a practical option for procedural sedation in colonoscopy. OBJECTIVE: To test the hypothesis that remimazolam could provide a noninferior discharge time to propofol for ambulatory colonoscopy. DESIGN: A prospective, randomised, double-blind, noninferiority clinical trial. SETTING: Ambulatory endoscopy centre. PATIENTS: A total of 132 adult participants undergoing ambulatory colonoscopy were enrolled. INTERVENTIONS: Participants were randomly assigned in a 1 : 1 ratio to receive propofol or remimazolam for sedation. MAIN OUTCOME MEASURES: The primary outcome was discharge time after a colonoscopy, assessed using the Modified Postanaesthetic Discharge Scoring System scale. Secondary outcomes included induction time, emergence time, the extent of recovery upon arrival in the postanaethesia care unit, fatigue, endoscopist and patient satisfaction and adverse events. RESULTS: The median discharge time was 24 min in the remimazolam group versus 21 min in the propofol group, with a difference of 2 min [95% confidence interval (CI), 0 to 4 min], meeting the criteria for noninferiority. Injection pain occurred in 11 of 66 (17%) participants receiving remimazolam versus 32 of 66 (49%) participants receiving propofol ( P  < 0.001); hypotension occurrence was 20% versus 47%, ( P  < 0.001), respectively, and bradycardia 6% versus 20%, ( P  = 0.019), respectively. Compared with propofol, the patient satisfaction score was higher in the remimazolam group ( P  < 0.001). CONCLUSION: For sedation in ambulatory colonoscopy, compared with propofol, remimazolam provides a noninferior discharge time. Furthermore, remimazolam is associated with less injection pain, lower risks of hypotension and bradycardia, and improved patient satisfaction. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2100048678.

Sarcoplasmic and myofibrillar phosphoproteins profile of beef M. longissimus thoracis with different pHu at different days postmortem.

BACKGROUND: The abnormal ultimate pH (pHu ) in postmortem muscles affect the meat quality and results in substantial economic losses. Dark, firm, and dry (DFD) meat linked with the higher postmortem pHu values and exhibited many quality issues such as dark color, tough texture and shorter shelf life. This research aimed to investigate the effect of protein phosphorylation on variations in beef pHu in order to explore the possible mechanisms underlying DFD meat formation. RESULTS: Glycogen and lactate contents were higher, while L* and a* were lower in high pHu beef. Shear force was higher in intermediate pHu group. Global phosphorylation of sarcoplasmic proteins was higher in low pHu samples on day 1 and of myofibrillar proteins was higher in intermediate pHu meat on days 1 and 2 postmortem. Sarcoplasmic protein bands with different phosphorylation levels were identified as containing some glycometabolism and stress response proteins and phosphorylated myofibrillar protein bands were identified sarcomeric and metabolic proteins. CONCLUSIONS: Phosphorylation of multiple proteins of glycolytic pathway and contractile machinery may play critical roles in development of DFD beef. © 2021 Society of Chemical Industry.

Ten-Year Change in Disorders of Consciousness: A Bibliometric Analysis.

Objectives: Disorders of consciousness (DoC) is a dynamic and challenging discipline, presenting intriguing challenges to clinicians and neurorehabilitation specialists for the lack of reliable assessment methods and interventions. Understanding DoC keeps pace with scientific research is urgent to need. We quantitively analyzed publications on DoC over the recent 10 years via bibliometrics analysis, to summarize the intellectual structure, current research hotspots, and future research trends in the field of DoC. Methods: Literature was obtained from the Science Citation Index Expanded of Web of Science Core Collection (WoSCC). To illustrate the knowledge structure of DoC, CiteSpace 5.8.R3 was used to conduct a co-occurrence analysis of countries, institutions, and keywords, and a co-citation analysis of references and journals. Also, Gephi 0.9.2 contributed to the author and co-cited author analysis. We found the most influential journals, authors, and countries and the most talked about keywords in the last decade of research. Results: A total of 1919 publications were collected. Over the past 10 years, the total number of annual publications has continued to increase, with the largest circulation in 2018. We found most DoC research and close cooperation originated from developed countries, e.g., the USA, Canada, and Italy. Academics from Belgium appear to have a strong presence in the field of DoC. The most influential journals were also mainly distributed in the USA and some European countries. Conclusions: This bibliometric study sheds light on the knowledge architecture of DoC research over the past decade, reflecting current hotspots and emerging trends, and providing new insights for clinicians and academics interested in DoC. The hot issues in DoC were diagnosing and differentiating the level of consciousness, and detecting covert awareness in early severe brain-injured patients. New trends focus on exploring the recovery mechanism of DoC and neuromodulation techniques.

Identification of novel key genes associated with the metastasis of prostate cancer based on bioinformatics prediction and validation.

BACKGROUND: Metastatic prostate cancer (PCa) is a lethal tumor. However, the molecular mechanisms underlying PCa progression have not been fully elucidated. METHODS: Transcriptome expression profiling and clinical information on primary and metastatic PCa samples were obtained from TCGA. R software was used to screen the DEGs, and LASSO logistical regression method was utilized to identify the pivotal PCa metastasis-related DEGs. The transcriptional expression levels of the key genes were analyzed using the UALCAN database, and the corresponding protein expression were validated by Immunohistochemistry (IHC). Survival analysis of the key genes was performed using the GEPIA database. Wound healing assay and Transwell assay were conducted to determine whether knockdown of the key genes influence the migration and invasion abilities of PCa cells (22Rv1 and PC3). GSEA was performed to predict key genes-mediated signaling pathways for the development of PCa. Western blotting was used to evaluate the expression changes of E-cadherin, Twist1, and Vimentin in PCa cells with the key genes silencing. An in vivo mouse metastatic model for PCa was also generated to verify the important role of ISG15 and CST2 in PCa metastasis. RESULTS: A comparison between primary and metastatic PCa tissues was conducted, and 19 DEGs were screened. Among these, three key genes were identified that might be closely associated with PCa progression according to the LASSO logistical analysis, namely ISG15, DNAH8, and CST2. Further functional experiments revealed that knockdown of ISG15 and CST2 suppressed wound healing, migration, and invasion of PCa cells. To explore the molecular mechanism of ISG15 and CST2 in the development of PCa, GSEA was performed, and it was found that both genes play crucial roles in cell adhesion molecules, extracellular matrix-receptor interaction, and focal adhesion. Western blotting results exhibited that inhibiting ISG15 and CST2 led to increase the expression of E-cadherin and decrease the expression of Twist1 and Vimentin. Additionally, the metastatic in vivo study demonstrated that both PC3 and 22Rv1 cells expressing with luciferase-shISG15 and luciferase-shCST2 had significantly lower detectable bioluminescence than that in the control PCa cells. CONCLUSION: ISG15 and CST2 may participate in PCa metastasis by regulating the epithelial-mesenchymal transition (EMT) signaling pathway. These findings may help to better understand the pathogenetic mechanisms governing PCa and provide promising therapeutic targets for metastatic PCa therapy.

Comparison of clinical performance of four gastrointestinal bleeding risk scores in Chinese patients with atrial fibrillation receiving oral anticoagulants.

Gastrointestinal bleeding is the most common bleeding complication during anticoagulant therapy. A reliable bleeding risk score can help the clinician assess risk of bleeding in individual patients and select the anticoagulant regimen. This study retrospectively analyzed the data of patients with atrial fibrillation who received anticoagulant therapy from July 2015 to December 2018 at two centers-the Fujian Medical University Union Hospital and Fuzhou Second Hospital Affiliated to Xiamen University. Demographic data, clinical findings, and laboratory results were collected from the hospital records. Patients were followed up for 6 months. The performance of four bleeding risk scores (New Score, RIETE Score, Cuschieri et al. Score, de Groot et al. Score) for prediction of gastrointestinal bleeding was assessed using the area under the curve. A total of 3462 patients (mean age, 66.3 ± 11.5 years; 59.6% males; 1055 direct oral anticoagulants users and 2407 warfarin users) were followed up for 6 months. While 99/3462 (2.9%) patients had gastrointestinal bleeding. The area under the curves for the New, RIETE, Cuschieri et al., de Groot et al. scores were 0.652 (95% CI 0.576-0.728), 0.862 (95% CI 0.809-0.914), 0.606 (95% CI 0.527-0.685), and 0.873 (95% CI 0.816-0.929), respectively. Among the four BRSs evaluated, the RIETE score and the de Groot et al. score appear to have the good predictive value, while the NEW score and the Cuschieri et al. score did not sufficiently predict gastrointestinal bleeding risk within the study Chinese population.

Improvement of analgesic efficacy for total hip arthroplasty by a modified ultrasound-guided supra-inguinal fascia iliaca compartment block.

BACKGROUND: Fascia iliaca compartment block (FICB) is an anterior approach to the lumbar plexus block and provides the effective adjunctive analgesia for total hip arthroplasty (THA). METHODS: As a case series study, 28 patients (≥ 65 years old) with THA were received a modified in-plane ultrasound-guided supra-inguinal (S-FICB) as an analgesic adjunct to evaluate the analgesic effectiveness and the local anesthetic diffusion with magnetic resonance imaging (MRI). A combination of propofol and sufentanil was administered to conduct target-controlled infusion. RESULTS: The pain scores were 1 (0-4), 2 (1-5), 3 (1-6) and 3 (1-6) at 4, 8, 12, and 24 h. The cumulative opioids were 8 (8-12), 18 (16-32), 28 (24-54) and 66 (48-104) mg of i.v. morphine equivalents at 4, 8, 12, and 24 h. The patient-controlled analgesia (PCA) times were 0 (0-1), 1 (0-2), 2 (0-5) and 5 (3-8) at 4, 8, 12, and 24 h. In lateral, anterior and medial part of thigh, the sensory blockade in 28 patients was 23 (82 %), 21 (75 %) and 19 (68 %) at 5 min; 28 (100 %) at 10 and 20 min. Motor blockade of femoral nerve (FN) and obturator nerve (ON) was present in 13 (46 %) and 3 (11 %) patients at 5 min, 24 (86 %) and 9 (32 %) at 10 min, 26 (93 %) and 11 (39 %) at 20 min. Injectate permeated to the FN and extended superiorly over the surface of iliac muscle (IM) and pectineus muscle (PM) in all patients. CONCLUSIONS: The modified S-FICB has provided an effective postoperative analgesic adjunct after THA with the satisfactory blockade of femoral (FN), obturator (ON) and sciatic (SN) nerves, especially for ON, when compared with the existing techniques.

LncRNA TUG1 alleviates cardiac hypertrophy by targeting miR-34a/DKK1/Wnt-ß-catenin signalling.

The current study was designed to explore the role and underlying mechanism of lncRNA taurine up-regulated gene 1 (TUG1) in cardiac hypertrophy. Mice were treated by transverse aortic constriction (TAC) surgery to induce cardiac hypertrophy, and cardiomyocytes were treated by phenylephrine (PE) to induce hypertrophic phenotype. Haematoxylin-eosin (HE), wheat germ agglutinin (WGA) and immunofluorescence (IF) were used to examine morphological alterations. Real-time PCR, Western blots and IF staining were used to detect the expression of RNAs and proteins. Luciferase assay and RNA pull-down assay were used to verify the interaction. It is revealed that TUG1 was up-regulated in the hearts of mice treated by TAC surgery and in PE-induced cardiomyocytes. Functionally, overexpression of TUG1 alleviated cardiac hypertrophy both in vivo and in vitro. Mechanically, TUG1 sponged and sequestered miR-34a to increase the Dickkopf 1 (DKK1) level, which eventually inhibited the activation of Wnt/ß-catenin signalling. In conclusion, the current study reported the protective role and regulatory mechanism of TUG1 in cardiac hypertrophy and suggested that TUG1 may serve as a novel molecular target for treating cardiac hypertrophy.

Intranasal dexmedetomidine versus oral midazolam premedication to prevent emergence delirium in children undergoing strabismus surgery: A randomised controlled trial.

BACKGROUND: Dexmedetomidine is being used increasingly as a premedicant in the paediatric population. However, the effectiveness of pre-operative intranasal dexmedetomidine premedication, compared with oral midazolam, for emergence delirium is not well characterised. OBJECTIVE: To identify the effectiveness of pre-operative intranasal dexmedetomidine for emergence delirium in the paediatric patient population following general anaesthesia. DESIGN: A prospective, randomised, double-blind, parallel-group, placebo-controlled trial. SETTING: Single university teaching hospital, from September 2013 to August 2014. PATIENTS: One hundred and fifty-six patients undergoing anaesthesia for strabismus surgery were included in the study. INTERVENTION: Patients were randomised in a 1 : 1 : 1 ratio to receive premedication with intranasal dexmedetomidine 2 µg kg (the dexmedetomidine group), oral midazolam 0.5 mg kg (the midazolam group), or 0.9% saline (the placebo group). MAIN OUTCOME MEASURES: The primary outcome was the incidence of emergence delirium assessed by the Paediatric Anaesthesia Emergence Delirium scale. Secondary outcomes included the quality of the inhalational induction, emergence time, postoperative pain intensity, length of stay in the postanaesthesia care unit, the incidence of postoperative nausea or vomiting (PONV) and parents' satisfaction. RESULTS: The incidence of emergence delirium was lower in patients given dexmedetomidine compared with that in patients given midazolam (11.5 versus 44%, relative risk = 0.262, 95% confidence interval 0.116 to 0.592) or 0.9% saline (11.5 versus 49%, relative risk = 0.235, 95% confidence interval 0.105 to 0.525). Likewise, the incidence of PONV was lower in the dexmedetomidine group (3.8%) than that in the midazolam (22%; P = 0.006) or placebo (29.4%; P < 0.001) groups. However, there was no difference among the groups concerning postoperative pain scores and length of postanaesthesia care unit stay. CONCLUSION: In paediatric patients undergoing strabismus surgery intranasal dexmedetomidine 2 µg kg premedication decreases the incidence of emergence delirium and PONV, and improves parents' satisfaction compared with oral midazolam. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT01895023).