Nivolumab combined docetaxel versus nivolumab in patients with previously treated nonsmall cell lung cancer: a phase 2 study.

The current standard second-line treatment is immune checkpoint inhibitors monotherapy for nonsmall cell lung cancer (NSCLC) patients. The objective of this phase 2 study was to evaluate the efficacy and safety of nivolumab plus docetaxel compared with nivolumab monotherapy for second-line therapy in immunotherapy-naive patients with advanced NSCLC. Progression-free survival (PFS) was the primary endpoint of this phase 2 study. Patients were randomized to receive nivolumab plus docetaxel or nivolumab monotherapy. From July 2019 to June 2022, a total of 22 patients were recruited, with significantly longer median PFS observed in the nivolumab plus docetaxel group (4.0 months) compared to the nivolumab group (2.0 months), P  = 0.0019. The study was closed in June 2022 due to slow recruitment. The objective response rate was 10.0% [95% confidence interval (CI), 0-28.6] in the nivolumab group and 25% (95% CI, 0.5-49.5) in the nivolumab + docetaxel group ( P  = 0.346). Disease control was significantly higher in the nivolumab plus docetaxel arm (40.0% versus 83.3%, P  = 0.035). There was also an improvement in overall survival (OS) in the nivolumab + docetaxel arm, but this was not statistically significant (10.0 months versus 7.2 months, P  = 0.129). The addition of docetaxel to nivolumab was well-tolerated, with adverse events more common in the combination group. Despite the small sample size, the results suggest that the addition of docetaxel to nivolumab may be a promising treatment option for NSCLC patients progressing on platinum-based chemotherapy, with trends towards improved OS observed.

Epidemiology and drug resistance analysis of bloodstream infections in an intensive care unit from a children's medical center in Eastern China for six consecutive years.

BACKGROUND: Children in the intensive care unit (ICU) who suffer from severe basic diseases and low immunity are usually in critical condition. It is crucial to assist clinicians in selecting the appropriate empirical antibiotic therapies for clinical infection control. METHODS: We retrospectively analyzed data from 281 children with bloodstream infection (BSI). Comparisons of basic data, pathogenic information, and drug resistance of the main bacteria were conducted. RESULTS: We detected 328 strains, including Gram-positive bacteria (223, 68%), mainly coagulase-negative Staphylococci (CoNS); Gram-negative bacteria (91, 27.7%); and fungi (14, 4.3%). The results of the binary logistic regression analysis showed that the main basic disease was an independent risk factor for death. Compared with Escherichia coli, Klebsiella pneumoniae exhibited a higher proportion of extended-spectrum ß-lactamases (ESBLs), and its resistance to some ß-lactamides and quinolones antibiotics were lower. Twenty-seven isolates of multidrug-resistant (MDR) bacteria were detected, of which carbapenem-resistant Acinetobacter baumannii (CRAB) accounted for the highest proportion (13, 48.2%). CONCLUSIONS: CoNS was the principal pathogen causing BSI in children in the ICU of children, and Escherichia coli was the most common Gram-negative pathogen. The main basic disease was an independent risk factor for death. It is necessary to continuously monitor patients with positive blood cultures, pay special attention to detected MDR bacteria, and strengthen the management of antibiotics and prevention and control of nosocomial infections.

Deep learning enables the discovery of a novel cuproptosis-inducing molecule for the inhibition of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers in the world. The therapeutic outlook for HCC patients has significantly improved with the advent and development of systematic and targeted therapies such as sorafenib and lenvatinib; however, the rise of drug resistance and the high mortality rate necessitate the continuous discovery of effective targeting agents. To discover novel anti-HCC compounds, we first constructed a deep learning-based chemical representation model to screen more than 6 million compounds in the ZINC15 drug-like library. We successfully identified LGOd1 as a novel anticancer agent with a characteristic levoglucosenone (LGO) scaffold. The mechanistic studies revealed that LGOd1 treatment leads to HCC cell death by interfering with cellular copper homeostasis, which is similar to a recently reported copper-dependent cell death named cuproptosis. While the prototypical cuproptosis is brought on by copper ionophore-induced copper overload, mechanistic studies indicated that LGOd1 does not act as a copper ionophore, but most likely by interacting with the copper chaperone protein CCS, thus LGOd1 represents a potentially new class of compounds with unique cuproptosis-inducing property. In summary, our findings highlight the critical role of bioavailable copper in the regulation of cell death and represent a novel route of cuproptosis induction.

A Novel Ultrasound Method of Evaluating Dynamic Extrusion of Lateral Meniscus in Healthy Population: Different Patterns of Dynamic Extrusion Revealed Between Lateral and Medial Meniscus.

OBJECTIVES: To establish a reliable ultrasound (US) method of evaluating dynamic extrusion of lateral meniscus in healthy population, and to investigate the pattern of dynamic meniscus extrusion (ME) in lateral meniscus under loading conditions. METHODS: The lateral ME was examined via US method in unloaded, double-leg standing, and single-leg standing positions. Two different US measurement methods were compared to the magnetic resonance imaging (MRI) results to determine the optimal measurement methods. The US results obtained by different researchers were tested for interobserver consistency and the results obtained by the same researcher on two separate days were tested for intraobserver consistency. The patterns of dynamic extrusion were compared between medial and lateral sides. RESULTS: A total of healthy 44 volunteers were included in the study, with 86 knees assessed by US, and 25 knees evaluated by MRI. The US evaluation of dynamic lateral ME demonstrated excellent interobserver and intraobserver reliability. The US measurements using method A were consistent with the MRI results with no significant difference (P = .861, intraclass correlation coefficient [ICC] = 0.868), while method B underestimated the lateral ME compared to MRI (P = .001, ICC = 0.649). Lateral ME decreased slightly from unloaded (1.0 ± 0.8 mm) to single-leg standing position (0.8 ± 0.8 mm), whereas medial ME increased significantly in both double-leg and single-leg standing positions (2.4 ± 0.7 mm, 2.6 ± 0.7 mm). CONCLUSION: A novel US evaluation method of lateral ME was established with reliable and accurate results compared to the MRI. Lateral ME in healthy populations decreased slightly as the loadings increased, which was different from the pattern of dynamic extrusion in medial meniscus.

Unilateral levator avulsion increases the risk of de novo stress urinary incontinence after cystocele repair.

INTRODUCTION: Patients without concurrent baseline stress urinary incontinence (SUI) can develop de novo SUI after transvaginal mesh surgery (TVM) for cystocele repair. Surgeons should be aware of de novo SUI risk factors after TVM. METHODS: A total of 1124 women who were underwent TVM surgeries were recruited and assessed for eligibility from January 1, 2012 to April 30, 2021. All data related to patients and surgeries was collected, which included general conditions, clinical examination, surgery records, and follow-up results. Patients were divided into three groups according to follow-up results and data were compared with each group. The relative risk (RR) of de novo SUI with levator avulsion was also calculated. RESULTS: Three hundred thirty-six patients were included in this study. They were divided into no complication group (n = 249), de novo SUI group (n = 68), and other complications group (n = 19). It seemed elder or obese women had a higher risk of de novo SUI after TVM (p < 0.05). In de novo SUI group, incidence of levator avulsion before surgery were higher than the other two groups (p = 0.001). TVM can significantly change a prolapse to point Aa and Ba on POP-Q quantification system (p < 0.05). RR ratios of de novo SUI with unilateral avulsion group is 2.60 (95% confidence interval [CI] 1.39-4.87), and 2.58 (95%CI 0.82-8.15) for bilateral group. CONCLUSION: Unilateral levator avulsion, instead of bilateral levator avulsion, is a risk factor of de novo SUI after cystocele repair surgery.

Progress on CRISPR/Cas9 system in the genetic improvement of livestock and poultry.

CRISPR/Cas9 gene editing technology, as a highly efficient genome editing method, has been extensively employed in the realm of animal husbandry for genetic improvement. With its remarkable efficiency and precision, this technology has revolutionized the field of animal husbandry. Currently, CRISPR/Cas9-based gene knockout, gene knock-in and gene modification techniques are widely employed to achieve precise enhancements in crucial production traits of livestock and poultry species. In this review, we summarize the operational principle and development history of CRISPR/Cas9 technology. Additionally, we highlight the research advancements utilizing this technology in muscle growth and development, fiber growth, milk quality composition, disease resistance breeding, and animal welfare within the livestock and poultry sectors. Our aim is to provide a more comprehensive understanding of the application of CRISPR/Cas9 technology in gene editing for livestock and poultry.

Novel beagle model of gastric local fibrotic target lesions for the evaluation and training of endoscopic techniques.

BACKGROUND: Novel endoscopic techniques used in the treatment of gastric lesions with local submucosal fibrosis need preclinical evaluation and training due to safety limitations. Therefore, the purpose of our study was to establish an animal model of gastric local fibrotic target lesions and assess its feasibility in the evaluation and training of endoscopic techniques. METHODS: In six experimental beagles, a 50% glucose solution was injected into three submucosal areas of the fundus, body, and antrum of the stomach to create gastric local fibrotic target lesions (experimental group). On post-injection day (PID) 7, the injection sites were assessed endoscopically to confirm the presence of submucosal fibrosis formation, and the dental floss clip traction assisted endoscopic submucosal dissection (DFC-ESD) procedure was performed on the gastric local fibrotic target lesions to confirm its feasibility after endoscopic observation. The normal gastric mucosa of six control beagles underwent the same procedure (control group). All the resected specimens were evaluated by histological examination. RESULTS: All 12 beagles survived without postoperative adverse events. On PID 7, 16 ulcer changes were observed at the injection sites (16/18) under the endoscope, and endoscopic ultrasonography confirmed the local submucosal fibrosis formation in all ulcer lesions. The subsequent DFC-ESD was successfully performed on the 32 gastric target lesions, and the mean submucosal dissection time in the ulcer lesions was greater than that in the normal gastric mucosa (15.3 ± 5.6 vs. 6.8 ± 0.8 min; P < 0.001). There was no difference in rates of en bloc resection, severe hemorrhage, or perforation between the two groups. Histological analysis of the ulcer lesions showed the absence of epithelial or muscularis mucosae and extensive submucosal fibrous tissue proliferations compared with normal gastric mucosa. Overall, endoscopists had high satisfaction with the realism and feasibility of the animal model. CONCLUSION: We developed a novel animal model of gastric local fibrotic target lesions to simulate difficult clinical situations, which strongly appeared to be suitable for the preclinical evaluation and learning of advanced endoscopic techniques.

Construction of an endoplasmic reticulum stress-related signature in lung adenocarcinoma by comprehensive bioinformatics analysis.

BACKGROUND: Lung Adenocarcinoma (LUAD) is a major component of lung cancer. Endoplasmic reticulum stress (ERS) has emerged as a new target for some tumor treatments. METHODS: The expression and clinical data of LUAD samples were downloaded from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) database, followed by acquiring ERS-related genes (ERSGs) from the GeneCards database. Differentially expressed endoplasmic reticulum stress-related genes (DE-ERSGs) were screened and used to construct a risk model by Cox regression analysis. Kaplan-Meier (K-M) curves and receiver operating characteristic (ROC) curves were plotted to determine the risk validity of the model. Moreover, enrichment analysis of differentially expressed genes (DEGs) between the high- and low- risk groups was conducted to investigate the functions related to the risk model. Furthermore, the differences in ERS status, vascular-related genes, tumor mutation burden (TMB), immunotherapy response, chemotherapy drug sensitivity and other indicators between the high- and low- risk groups were studied. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the mRNA expression levels of prognostic model genes. RESULTS: A total of 81 DE-ERSGs were identified in the TCGA-LUAD dataset, and a risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was constructed by Cox regression analysis. K-M and ROC analyses showed that the high-risk group had a low survival, and the Area Under Curve (AUC) of ROC curves of 1-, 3- and 5-years overall survival was all greater than 0.6. In addition, functional enrichment analysis suggested that the risk model was related to collagen and extracellular matrix. Furthermore, differential analysis showed vascular-related genes FLT1, TMB, neoantigen, PD-L1 protein (CD274), Tumor Immune Dysfunction and Exclusion (TIDE), and T cell exclusion score were significantly different between the high- and low-risk groups. Finally, qRT-PCR results showed that the mRNA expression levels of 6 prognostic genes were consistent with the analysis. CONCLUSION: A novel ERS-related risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was developed and validated, which provided a theoretical basis and reference value for ERS-related fields in the study and treatment of LUAD.

[Postoperative Delirium in Patients on Cardiopulmonary Bypass for Cardiovascular Surgeries: Incidence and Influencing Factors].

Objective: To investigate the incidence and influencing factors of postoperative delirium (POD) and subsyndromal delirium (SSD) in patients connected to cardiopulmonary bypass during cardiovascular surgeries. Methods: We collected the general data and the data for the perioperative hematological, physiological, and biochemical indicators and the surgical and therapeutic conditions of patients connected to cardiopulmonary bypass during the course of cardiovascular surgeries conducted at a tertiary-care hospital in Hubei province between May 2022 and September 2022. The outcome indicators, including the incidence of POD and SSD, were assessed with the Nursing Delirium Screening Scale (Nu-DESC). Multinomial logistic regression was performed to analyze the influencing factors of patients with different statuses of POD and SSD. Results: Among the 202 patients, the incidence of SSD, SSD progressing to POD, and no POD or SSD (ND) progressing to POD were 13.4%, 6.4%, and 34.2%, respectively. Regression analysis showed that, with ND patients as the controls, the influencing factors for SSD were preoperative blood glucose (odds ratio [ OR]=0.38, 95% confidence interval [ CI]: 0.19-0.76), intraoperative platelet transfusion ( OR=0.37, 95% CI: 0.15-0.92), intraoperative etomidate ( OR=0.93, 95% CI: 0.87-0.98), and postoperative total bilirubin level ( OR=1.04, 95% CI: 1.01-1.07). For the progression of SSD to POD, the influencing factors were age ( OR=1.09, 95% CI: 1.01-1.17), ASA classification of IV and above ( OR=10.72, 95% CI: 1.85-62.08), intraoperative dexmedetomidine ( OR=1.01, 95% CI: 1.003-1.02), and the duration of mechanical ventilation ( OR=1.04, 95% CI: 1.01-1.07). For the progression of ND to POD, the influencing factors were age ( OR=1.06, 95% CI: 1.02-1.10), middle or high school education ( OR=0.35, 95% CI: 0.15-0.83), and the duration of mechanical ventilation ( OR=1.04, 95% CI: 1.01-1.07). Conclusion: Age, education, ASA classification, preoperative blood glucose, intraoperative platelet transfusion, intraoperative etomidate, intraoperative dexmedetomidine, postoperative total bilirubin, and the duration of mechanical ventilation are influencing factors for different statuses of POD and SSD among patients connected to cardiopulmonary bypass when they are undergoing cardiovascular surgeries. The influencing factors vary across groups of patients with different statuses of POD and SSD. Therefore, we should accurately assess the risk factors of patients with different statuses of POD and SSD and carry out corresponding interventions, thereby preventing or reducing the occurrence of POD and SSD, and ultimately promoting enhanced recovery after surgery.

Intermolecular Enantioselective Benzylic C(sp3 )-H Amination by Cationic Copper Catalysis.

Chiral benzylic amines are privileged motifs in pharmacologically active molecules. Intramolecular enantioselective radical C(sp3 )-H functionalization by hydrogen-atom transfer has emerged as a straightforward, powerful tool for the synthesis of chiral amines, but methods for intermolecular enantioselective C(sp3 )-H amination remain elusive. Herein, we report a cationic copper catalytic system for intermolecular enantioselective benzylic C(sp3 )-H amination with peroxide as an oxidant. This mild, straightforward method can be used to transform an array of feedstock alkylarenes and amides into chiral amines with high enantioselectivities, and it has good functional group tolerance and broad substrate scope. More importantly, it can be used to synthesize bioactive molecules, including chiral drugs. Preliminary mechanistic studies indicate that the amination reaction involves benzylic radicals generated by hydrogen-atom transfer.

Multi-view manifold regularized compact low-rank representation for cancer samples clustering on multi-omics data.

BACKGROUND: The identification of cancer types is of great significance for early diagnosis and clinical treatment of cancer. Clustering cancer samples is an important means to identify cancer types, which has been paid much attention in the field of bioinformatics. The purpose of cancer clustering is to find expression patterns of different cancer types, so that the samples with similar expression patterns can be gathered into the same type. In order to improve the accuracy and reliability of cancer clustering, many clustering methods begin to focus on the integration analysis of cancer multi-omics data. Obviously, the methods based on multi-omics data have more advantages than those using single omics data. However, the high heterogeneity and noise of cancer multi-omics data pose a great challenge to the multi-omics analysis method. RESULTS: In this study, in order to extract more complementary information from cancer multi-omics data for cancer clustering, we propose a low-rank subspace clustering method called multi-view manifold regularized compact low-rank representation (MmCLRR). In MmCLRR, each omics data are regarded as a view, and it learns a consistent subspace representation by imposing a consistence constraint on the low-rank affinity matrix of each view to balance the agreement between different views. Moreover, the manifold regularization and concept factorization are introduced into our method. Relying on the concept factorization, the dictionary can be updated in the learning, which greatly improves the subspace learning ability of low-rank representation. We adopt linearized alternating direction method with adaptive penalty to solve the optimization problem of MmCLRR method. CONCLUSIONS: Finally, we apply MmCLRR into the clustering of cancer samples based on multi-omics data, and the clustering results show that our method outperforms the existing multi-view methods.

Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC.

BACKGROUND: The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. MATERIALS AND METHODS: The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. RESULTS: Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p = 0.05). There was no significant difference in grade 3-4 adverse events (AEs) between the two groups (p = 0.253). CONCLUSIONS: The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

Predicting miRNA-disease associations via layer attention graph convolutional network model.

BACKGROUND: MiRNA is a class of non-coding single-stranded RNA molecules with a length of approximately 22 nucleotides encoded by endogenous genes, which can regulate the expression of other genes. Therefore, it is very important to predict the associations between miRNA and disease. Predecessors developed a new prediction method of drug-disease association, and it achieved good results. METHODS: In this paper, we introduced the method of LAGCN to identify potential miRNA-disease associations. First, we integrate three associations into a heterogeneous network, such as the known miRNA-disease association, miRNA-miRNA similarities and disease-disease similarities, next we apply graph convolution network to learn the embedding of miRNA and disease. We use an attention mechanism to combine embedding from multiple convolution layers. Unobserved miRNA-disease associations are scored based on integrated embedding. RESULTS: After fivefold cross-validations, the value of AUC is reached 0.9091, which is higher than other prediction methods and baseline methods. CONCLUSIONS: In this paper, we introduced the method of LAGCN to identify potential miRNA-disease associations. LAGCN has achieved good performance in predicting miRNA-disease associations, and it is superior to other association prediction methods and baseline methods.

The structural change and influencing factors of carbon transfer network in global value chains.

Based on the gross trade accounting method and WIOD data, this paper quantifies the global carbon transfer from 2000 to 2014. The social network analysis and temporal exponential random graph model (TERGM) are employed to investigate the structural change and influencing factors of global carbon transfer network from a global value chains (GVCs) perspective. Results show that the deepening of the GVC division connection has enhanced the relations in global carbon transfer network, and the low reciprocity and high disassortativity lie in the difference in GVC division positions among economies. Block model analysis manifests that Plate Ⅱ acts as the engine plate in the network which consists of China and the other four economies. The GVC division connection and relative GVC division position significantly facilitate the formation of carbon emission transfer relations. Moreover, economies' attribute effects and endogenous network structure effects are non-negligible important determinants of network formation.

New insight into chronic pruritus' characteristics and association with the demographic characteristics and sleep of community-dwelling older adults in Taiwan.

This study aimed to understand the characteristics of chronic pruritus (CP), its correlations with sleep quality and demographic characteristics, and its impacts on sleep of older adults. This study used convenience sampling to recruit adults aged 65 or older and living at home. The prevalence rate of CP in older adults was 25.8%. Most subjects with CP reported mild pruritus on 1-2 anatomical parts, especially the lower extremities. Overall, the five domains of CP were correlated with the seven components of sleep quality (r > .14; p > .05) except for sleep disturbance. The global itchy scores were significantly different between different sexes, educational attainments, and marital statuses (p<.05-.001). CP, sex, and the number of comorbid diseases significantly contributed to global sleep quality (ß = .26, -.19, .15, respectively; .000 ≤ p ≤ .011). This study provides new insight into the correlations of CP with marital status and educational attainment.

IPCARF: improving lncRNA-disease association prediction using incremental principal component analysis feature selection and a random forest classifier.

BACKGROUND: Identifying lncRNA-disease associations not only helps to better comprehend the underlying mechanisms of various human diseases at the lncRNA level but also speeds up the identification of potential biomarkers for disease diagnoses, treatments, prognoses, and drug response predictions. However, as the amount of archived biological data continues to grow, it has become increasingly difficult to detect potential human lncRNA-disease associations from these enormous biological datasets using traditional biological experimental methods. Consequently, developing new and effective computational methods to predict potential human lncRNA diseases is essential. RESULTS: Using a combination of incremental principal component analysis (IPCA) and random forest (RF) algorithms and by integrating multiple similarity matrices, we propose a new algorithm (IPCARF) based on integrated machine learning technology for predicting lncRNA-disease associations. First, we used two different models to compute a semantic similarity matrix of diseases from a directed acyclic graph of diseases. Second, a characteristic vector for each lncRNA-disease pair is obtained by integrating disease similarity, lncRNA similarity, and Gaussian nuclear similarity. Then, the best feature subspace is obtained by applying IPCA to decrease the dimension of the original feature set. Finally, we train an RF model to predict potential lncRNA-disease associations. The experimental results show that the IPCARF algorithm effectively improves the AUC metric when predicting potential lncRNA-disease associations. Before the parameter optimization procedure, the AUC value predicted by the IPCARF algorithm under 10-fold cross-validation reached 0.8529; after selecting the optimal parameters using the grid search algorithm, the predicted AUC of the IPCARF algorithm reached 0.8611. CONCLUSIONS: We compared IPCARF with the existing LRLSLDA, LRLSLDA-LNCSIM, TPGLDA, NPCMF, and ncPred prediction methods, which have shown excellent performance in predicting lncRNA-disease associations. The compared results of 10-fold cross-validation procedures show that the predictions of the IPCARF method are better than those of the other compared methods.

A review on partial-wave dynamics with chiral effective field theory and dispersion relation.

The description of strong interaction physics of low-lying resonances is out of the valid range of perturbative QCD. Chiral effective field theories (EFTs) have been developed to tackle the issue. Partial wave dynamics is the systematic tool to decode the underlying physics and reveal the properties of those resonances. It is extremely powerful and helpful for our understanding of the non-perturbative regime, especially when dispersion techniques are utilized simultaneously. Recently, plenty of exotic/ordinary hadrons have been reported by experiment collaborations, e.g. LHCb, Belle, and BESIII, etc. In this review, we summarize the recent progress on the applications of partial wave dynamics combined with chiral EFTs and dispersion relations, on related topics, with emphasis onππ,πK,πNandK̄Nscatterings.

Tension Stimulation of Tenocytes in Aligned Hyaluronic Acid/Platelet-Rich Plasma-Polycaprolactone Core-Sheath Nanofiber Membrane Scaffold for Tendon Tissue Engineering.

To recreate the in vivo niche for tendon tissue engineering in vitro, the characteristics of tendon tissue underlines the use of biochemical and biophysical cues during tenocyte culture. Herein, we prepare core-sheath nanofibers with polycaprolactone (PCL) sheath for mechanical support and hyaluronic acid (HA)/platelet-rich plasma (PRP) core for growth factor delivery. Three types of core-sheath nanofiber membrane scaffolds (CSNMS), consisting of random HA-PCL nanofibers (Random), random HA/PRP-PCL nanofibers (Random+) or aligned HA/PRP-PCL (Align+) nanofibers, were used to study response of rabbit tenocytes to biochemical (PRP) and biophysical (fiber alignment) stimulation. The core-sheath structures as well as other pertinent properties of CSNMS have been characterized, with Align+ showing the best mechanical properties. The unidirectional growth of tenocytes, as induced by aligned fiber topography, was confirmed from cell morphology and cytoskeleton expression. The combined effects of PRP and fiber alignment in Align+ CSNMS lead to enhanced cell proliferation rates, as well as upregulated gene expression and marker protein synthesis. Another biophysical cue on tenocytes was introduced by dynamic culture of tenocyte-seeded Align+ in a bioreactor with cyclic tension stimulation. Augmented by this biophysical beacon from mechanical loading, dynamic cell culture could shorten the time for tendon maturation in vitro, with improved cell proliferation rates and tenogenic phenotype maintenance, compared to static culture. Therefore, we successfully demonstrate how combined use of biochemical/topographical cues as well as mechanical stimulation could ameliorate cellular response of tenocytes in CSNMS, which can provide a functional in vitro environmental niche for tendon tissue engineering.

[Evidence of clinical randomized controlled trial study in treatment of acute cerebral infarction with traditional Chinese medicine in recent five years].

To systematically search and sort out the clinical randomized controlled trial(RCT) on the prevention and treatment of acute cerebral infarction with traditional Chinese medicine(TCM) by using the method of evidence map, and to understand the evidence distribution of related studies. CNKI, Wanfang, VIP, CBM, PubMed, EMbase, Cochrane Library and Web of Science were retrieved from January 2016 to September 2020, and literatures related to the prevention and treatment of acute cerebral infarction with traditional Chinese medicine were included. Text description combined with table and bubble chart were used to analyze the distribution characteristics of evidence. A total of 1 102 clinical articles in recent five years were retrieved. The annual trend of clinical study publication, study size, TCM therapy category and main scheme, and study literature quality were analyzed. We find that TCM treatment of acute cerebral infarction has become a hot topic of clinical research, the number of literature showed a trend of increased year by year, various means of intervention of TCM in the treatment of the advantages of increasingly highlight. Follow-up clinical research should highlight the characteristics of TCM: in the analysis of outcome indicators; increase the neuropsychological patients after stroke and cognitive ability, and the theory of combined treatment of TCM disease when thoughts; At the same time, the quality of clinical research needs to be improved. At present, there is still a lack of unified standards for the production of evidence map. This study is the first to explore the application of evidence map to summarize and display the clinical research status of TCM treatment of acute cerebral infarction, and combine it with the setting of priority areas of TCM clinical research, so as to provide a reference basis for determining the priority topic selection of TCM treatment optimization research.

[Analysis of status quo of outcome indicators of randomized controlled trials in treatment of acute ischemic stroke with acupuncture in recent three years].

To analyze the use of outcome indicators of randomized controlled trial(RCT) of acupuncture in the treatment of acute ischemic stroke in recent three years, so as to provide a basis for building a study on the core outcome indicators for the treatment of acute ischemic stroke with acupuncture. The RCTs of acupuncture treatment for acute ischemic stroke in recent three years were collec-ted through computer retrieval of eight Chinese and English databases and two clinical trial registries at home and abroad. Literature was screened out, and data was extracted. Risk of assessment bias tool Cochrane 6.1 was used for bias risk assessment, outcome indicators were summarized and analyzed. A total of 47 RCTs were included, and 3 studies were trials registration scheme. Outcome indicators were divided into 6 categories according to functional attributes, namely physical symptoms/signs, physical and chemical examination, quality of life, traditional Chinese medicine symptoms/syndromes, safety events and long-term prognosis. The study found that in addition to the common problems in previous studies covered by the status quo of outcome indicators selection of RCT of acupuncture in the treatment of acute ischemic stroke, there were also the other problems as follows: emphasis on macroscopic efficacy indicators but neglect of acupuncture specific indicators, lack of characteristic indicators and economic indicators of traditional Chinese medicine therapy, and unification of indicators measurement tool and measurement time point. In the future, the outcome indicators set for the treatment of acute ischemic stroke with acupuncture shall be established, and the core outcome indicators set shall be in line with the characteristics of traditional Chinese medicine treatment.