[Establishment and validation of a predictive model for postoperative pulmonary complications in elderly patients undergoing non-cardiac surgery].

Objective: To develop and validate a predictive model for postoperative pulmonary complications (PPCs) in elderly patients undergoing non-cardiac surgery. Methods: This retrospective study included 51 354 elderly patients over 65 years old who underwent non-cardiac surgery at the First Medical Center of Chinese PLA General Hospital from January 2009 to December 2018. The patients were randomly divided into a modeling group [n=41 084; 21 550 males, 19 534 females; age: 70 (67, 74) years] and an internal validation group [n=10 270; 5 458 males, 4 812 females; age: 70 (67, 74) years] at a ratio of 4∶1. Additionally, an external validation group of 14 378 patients [7 893 males, 6 845 females; age: 70 (67, 75) years] who underwent non-cardiac surgery at Henan Provincial People's Hospital between November 2014 and May 2022 was retrospectively included. Multivariate logistic regression were performed to identify factors associated with PPCs. A nomogram prediction model was constructed based on these factors and validated internally and externally. The model's performance and clinical applicability were assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curves. Results: Among the 51 354 elderly patients underwent general anesthesia for non-cardiac surgery, the incidence of PPCs was 17.5% (9 008/51 354). Multivariate logistic regression analysis reveals that anesthesia duration 130-<183 min (OR=1.858, 95%CI: 1.529-2.266), anesthesia duration 183-<250 min (OR=2.537, 95%CI: 2.079-3.108), anesthesia duration≥250 min(OR=3.533, 95%CI: 2.868-4.368), crystalloid infusion volume 1 400-<2 000 ml (OR=1.481, 95%CI: 1.204-1.829), crystalloid infusion volume 2 000-<9 000 ml (OR=1.776, 95%CI: 1.426-2.220), upper abdominal surgery (OR=1.658, 95%CI: 1.498-1.835), malignancy (OR=1.796, 95%CI: 1.606-2.012), fentanyl dosage 0.40-<0.55 mg (OR=1.404, 95%CI: 1.203-1.640), fentanyl dosage≥0.55 mg (OR=1.601, 95%CI: 1.386-1.854), prophylactic use of antibiotics (OR=7.897, 95%CI: 5.124-12.983), age (OR=1.039, 95%CI: 1.030-1.049), smoking (OR=1.124, 95%CI: 1.014-1.246), preoperative chest X-ray abnormalities (OR=2.139, 95%CI: 1.820-2.509) and intraoperative hypotension (OR=3.184, 95%CI: 2.120-4.795) were risk factors for PPCs, while elective surgery (OR=0.301, 95%CI: 0.220-0.417) was a protective factor. The nomogram model incorporating these factors had an area under the curve (AUC) of 0.757 (95%CI: 0.748-0.766, P=0.309) in the modeling group, 0.779 (95%CI: 0.760-0.796, P=0.171) in the internal validation group, and 0.778 (95%CI: 0.763-0.792, P<0.001) in the external validation group. Calibration curves and decision curves demonstrated good consistency and benefit of the model. Conclusion: The nomogram model which based on anesthesia duration, crystalloid infusion volume, upper abdominal surgery, malignancy, fentanyl dosage, prophylactic use of antibiotics, age, smoking, preoperative chest X-ray abnormalities, intraoperative hypotension and elective surgery provides strong predictive value and clinical utility for assessing the risk of PPCs in elderly patients undergoing non-cardiac surgery.

[Influence of disposable diaper dependence on emotional behavior and related factors of preschool-aged children].

Objective: To investigate the influence of disposable diaper dependence (DDD) on emotional behavior and related factors of preschool-aged children. Methods: A total of 3 000 preschool-aged children from 16 kindergartens in Zhengzhou of Henan Province from October 2019 to March 2020 were selected and their parents were investigated by using a basic information questionnaire (including usage of disposable diapers), Strengths and Difficulties Questionnaire (SDQ) and Children's Sleep Questionnaire (PSQ). The differences in baseline and clinical data were compared between the DDD children and normal children, and multiple linear regression models were used to analyze the factors associated with emotional behavior in DDD children. Results: A total of 3 000 questionnaires were distributed and 2 775 (92.50%) were valid. The children ranged in age from 3 to 5 years, including 1 438 boys (51.82%) and 1 337 girls (48.18%). There were 98 (3.53%) children in DDD group and 2 677 (96.47%) children in normal group. The proportion of children living in cities in the DDD group was 58.16%, significantly higher than that of 41.84% in the normal children group (P<0.001). The abnormal detection rate of various factors in SDQ in DDD children, from high to low, were hyperactivity (n=14, 14.29%), peer communication problems (n=12, 12.24%), prosocial behavior (n=11, 11.22%), emotional symptoms (n=10, 10.20%) and conduct problems (n=7, 7.14%). The detection rates of abnormal total difficulty scores in DDD group and normal children were 7.14% (7 cases) and 0.78% (21 cases), respectively, with statistically significant differences (P<0.001). The proportions of emotional symptoms and hyperactivity disorder in DDD group were higher than those in normal group, and the differences were statistically significant (P<0.05). The PSQ score of children in DDD group was 3.01±2.02 which was not significantly different from the PSQ score of the normal group (2.71±2.10, P=0.157). The multi-factor analysis showed that caregiver's education level (ß=-1.135,95%CI:-1.910 to -0.359), urinary incontinence (ß=2.222, 95%CI: 1.105-3.339), fecal incontinence (ß=3.833, 95%CI: 2.691-4.975), urinary and fecal incontinence (ß=5.522, 95%CI: 4.145-6.899), and recurrent urinary tract infections(ß=3.523,95%CI: 1.798-5.248)were the independent influencing factors of emotional behavioral problems in DDD children (P<0.05). Conclusions: Children with DDD are more likely to have emotional behavioral problems than normal children. Caregiver's education level, urinary incontinence and recurrent urinary tract infections were influencing factors of emotional behavioral problems in DDD children.

[Revision rate of periprosthetic joint infection post total hip or knee arthroplasty of 34 hospitals in China between 2015 and 2017: a multi-center survey].

Objective: To investigate the rate of periprosthetic joint infection (PJI) revision surgeries and clinical information of hip-/knee- PJI cases nationwide from 2015 to 2017 in China. Methods: An epidemiological investigation. A self-designed questionnaire and convenience sampling were used to survey 41 regional joint replacement centers nationwide from November 2018 to December 2019 in China. The PJI was diagnosed according to the Musculoskeletal Infection Association criteria. Data of PJI patients were obtained by searching the inpatient database of each hospital. Questionnaire entries were extracted from the clinical records by specialist. Then the differences in rate of PJI revision surgery between hip- and knee- PJI revision cases were calculated and compared. Results: Total of 36 hospitals (87.8%) nationwide reported data on 99 791 hip and knee arthroplasties performed from 2015 to 2017, with 946 revisions due to PJI (0.96%). The overall hip-PJI revision rate was 0.99% (481/48 574), and it was 0.97% (135/13 963), 0.97% (153/15 730) and 1.07% (193/17 881) in of 2015, 2016, 2017, respectively. The overall knee-PJI revision rate was 0.91% (465/51 271), and it was 0.90% (131/14 650), 0.88% (155/17 693) and 0.94% (179/18 982) in 2015, 2016, 2017, respectively. Heilongjiang (2.2%, 40/1 805), Fujian (2.2%, 45/2 017), Jiangsu (2.1%, 85/3 899), Gansu (2.1%, 29/1 377), Chongqing (1.8%, 64/3 523) reported relatively high revision rates. Conclusions: The overall PJI revision rate in 34 hospitals nationwide from 2015 to 2017 is 0.96%. The hip-PJI revision rate is slightly higher than that in the knee-PJI. There are differences in revision rates among hospitals in different regions.

Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing.

OBJECTIVES: To reveal the heterogeneity of different cell types of osteoarthritis (OA) synovial tissues at a single-cell resolution, and determine by novel methodology whether bulk-RNA-seq data could be deconvoluted to create in silico scRNA-seq data for synovial tissue analyses. METHODS: OA scRNA-seq data (102,077 synoviocytes) were provided by 17 patients undergoing total knee arthroplasty; 9 tissues with matched scRNA-seq and bulk RNA-seq data were used to evaluate six in silico gene deconvolution tools. Predicted and observed cell types and proportions were compared to identify the best deconvolution tool for synovium. RESULTS: We identified seven distinct cell types in OA synovial tissues. Gene deconvolution identified three (of six) platforms as suitable for extrapolating cellular gene expression from bulk RNA-seq data. Using paired scRNA-seq and bulk RNA-seq data, an "arthritis" specific signature matrix was created and validated to have a significantly better predictive performance for synoviocytes than a default signature matrix. Use of the machine learning tool, Cell-type Identification By Estimating Relative Subsets of RNA Transcripts x (CIBERSORTx), to analyze rheumatoid arthritis (RA) and OA bulk RNA-seq data yielded proportions of T cells and fibroblasts that were similar to the gold standard observations from RA and OA scRNA-seq data, respectively. CONCLUSION: This novel study revealed heterogeneity of synovial cell types in OA and the feasibility of gene deconvolution for synovial tissue.

Heat stress negatively affects the transcriptome related to overall metabolism and milk protein synthesis in mammary tissue of midlactating dairy cows.

Inadequate dry matter intake only partially accounts for the decrease in milk protein synthesis during heat stress (HS) in dairy cows. Our hypothesis is that reduced milk protein synthesis during HS in dairy cows is also caused by biological changes within the mammary gland. The objective of this study was to assess the hypothesis via RNA-Seq analysis of mammary tissue. Herein, four dairy cows were used in a crossover design where HS was induced for 9 days in environmental chambers. There was a 30-day washout between periods. Mammary tissue was collected via biopsy at the end of each environmental period (HS or pair-fed and thermal neutral) for transcriptomic analysis. RNA-Seq analysis revealed HS affected >2,777 genes (false discovery rate-adjusted P value < 0.05) in mammary tissue. Expression of main milk protein-encoding genes and several key genes related to regulation of protein synthesis and amino acid and glucose transport were downregulated by HS. Bioinformatics analysis revealed an overall decrease of mammary tissue metabolic activity by HS (especially carbohydrate and lipid metabolism) and an increase in immune activation and inflammation. Network analysis revealed a major role of TNF, IFNG, S100A8, S100A9, and IGF-1 in inducing/controlling the inflammatory response, with a central role of NF-κB in the process of immunoactivation. The same analysis indicated an overall inhibition of PPARγ. Collectively, these data suggest HS directly controls milk protein synthesis via reducing the transcription of metabolic-related genes and increasing inflammation-related genes.

Impact on the nutritional attributes of rice bran following various stabilization procedures.

Rice bran, a valuable byproduct of the rice milling process, has limitations in food industrial applications due to its instability during storage. This review summaries the methodology for stabilization and its impact on the nutritional properties of rice bran. A variety of treatments have been used and these include heat treatment, low-temperature storage, biological and chemical approaches and these will be discussed in terms of their ability to destroy/inhibit enzyme activity and improve storage performance of rice bran. More importantly, changes in the nutritional value of rice bran in terms of vitamins, polyphenols, tocopherols, flavonoids, free fatty acids caused by stabilization of rice bran will also be discussed. This review highlights the importance of appropriate design of processes for stabilization and controlling storage conditions to ensure quality of the rice bran and enhancing levels of phytochemicals in the bran for novel applications in functional foods.

Functional peptides derived from rice bran proteins.

Rice bran has been predominantly used in the feed industry, and only recently it has attracted greater attention in terms of human nutrition with increasing knowledge of its bioactivity. A growing interest is the analysis of physiologically active peptides derived from rice bran proteins. In this paper, the bioactivities of rice bran proteins hydrolysates and peptides are reviewed based on recent studies. These enzymatic hydrolysates and peptides exert various biological activities including antioxidant, antidiabetic, anticancer and inhibitory activity for angiotensin converting enzyme (ACE), which may ultimately prevent certain chronic diseases. Nevertheless, these functionalities can be highly associated with their corresponding structural characteristics, in particular specific sequences and molecular weight distribution. This article may facilitate the expansion of the prospective applications of the bioactive peptides in a number of fields and provide some clues of the relationship between peptides structure and functionality for future research.

Glucagon-like peptide-1 receptor agonists and fracture risk: a network meta-analysis of randomized clinical trials.

Our network meta-analysis analyzed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on fracture risk. By combining data from randomized controlled trials, we found that GLP-1 RAs were associated with a decreased bone fracture risk, and exenatide is the best option agent with regard to the risk of fracture. This study is registered with PROSPERO (CRD42018094433). INTRODUCTION: Data on the effects of GLP-1 RAs on fracture risk are conflicted. This study aimed to analyze the available evidence on the effects of GLP-1 RAs on fracture risk in type 2 diabetes mellitus patients. METHODS: Electronic databases were searched for relevant published articles, and unpublished studies presented at ClinicalTrials.gov were searched for relevant clinical data. All analyses were performed with STATA 12.0 and R software (Version 3.4.4). We estimated the risk ratio (RR) and 95% confidence interval (CI) by combining RRs for fracture effects of included trials. RESULTS: There were 54 eligible random control trials (RCTs) with 49,602 participants, including 28,353 patients treated with GLP-1 RAs. Relative to placebo, exenatide (RR, 0.17; 95% CI 0.03-0.67) was associated with lowest risk of fracture among other GLP-1 RAs. Exenatide had the highest probability to be the safest option with regard to the risk of fracture (0.07 ‰), followed by dulaglutide (1.04%), liraglutide (1.39%), albiglutide (5.61%), lixisenatide (8.07%), and semaglutide (18.72%). A statistically significant inconsistency was observed in some comparisons. CONCLUSION: The Bayesian network meta-analysis suggests that GLP-1 RAs were associated with a decreased bone fracture risk compared to users of placebo or other anti-hyperglycemic drugs in type 2 diabetes mellitus patients, and exenatide is the best option agent with regard to the risk of fracture.

Intra-articular injection of microRNA-140 (miRNA-140) alleviates osteoarthritis (OA) progression by modulating extracellular matrix (ECM) homeostasis in rats.

OBJECTIVE: Disruptions of extracellular matrix (ECM) homeostasis are key events in the pathogenesis of osteoarthritis (OA). MicroRNA-140 (miRNA-140) is expressed specifically in cartilage and regulates ECM-degrading enzymes. Our objective in this study was to determine if intra-articular injection of miRNA-140 can attenuate OA progression in rats. DESIGN: miRNA-140 levels in human normal and OA cartilage derived chondrocytes and synovial fluid were assessed by polymerase chain reaction (PCR). After primary human chondrocytes were transfected with miRNA-140 mimic or inhibitor, PCR and western blotting were performed to quantify Collagen II, MMP-13, and ADAMTS-5 expression. An OA model was induced surgically in rats, and subsequently treated with one single intra-articular injection of miRNA-140 agomir. At 4, 8, and 12 weeks after surgery, OA progression were evaluated macroscopically, histologically, and immunohistochemically in these rats. RESULTS: miRNA-140 levels were significantly reduced in human OA cartilage derived chondrocytes and synovial fluid compared with normal chondrocytes and synovial fluid. Overexpressing miRNA-140 in primary human chondrocytes promoted Collagen II expression and inhibited MMP-13 and ADAMTS-5 expression. miRNA-140 levels in rat cartilage were significantly higher in the miRNA-140 agomir group than in the control group. Moreover, behavioural scores, chondrocyte numbers, cartilage thickness and Collagen II expression levels in cartilage were significantly higher, while pathological scores and MMP-13 and ADAMTS-5 expression levels were significantly lower in the miRNA-140 agomir group than in the control group. CONCLUSION: Intra-articular injection of miRNA-140 can alleviate OA progression by modulating ECM homeostasis in rats, and may have potential as a new therapy for OA.

The arthropathic and functional impairment features of adult Kashin-Beck disease patients in Aba Tibetan area in China.

OBJECT: The purpose of the study was to analyze the features of arthropathic changes and functional impairments as well as the correlations between them for adult patients suffered with Kashin-Beck disease (KBD) in Aba Tibetan area of Sichuan Province, China. METHOD: Nine hundred and eighty-nine adult KBD patients in Aba KBD prevalence area were investigated. The arthropathic changes including arthritic pain (evaluated by visual analog pain score (VAS)), deformity, limited range of joint motion (ROM), as well as daily living and working function were examined, evaluated and analyzed. RESULTS: Ninety-two percent of patients suffered with multiple affected joints in both upper and lower extremities. The most frequently affected joints were knee (86.1%) and hand (77.2%). The most painful joints were knee (VAS 7.1 ± 1.9) and elbow (VAS 6.8 ± 2.1). Joint deformities most frequently represented as enlargement of interphalangeal joints (93.2%). Limitation of ROM occurred most frequently in hand (76.7%) and elbow (38.4%). Multiple linear regression analysis revealed that only joint pain (regression coefficient: -0.504, 95% confidence interval (CI): -0.820-0.188, P ＜ 0.001) and ROM (regression coefficient: 0.017, 95% CI: 0.011-0.024, P ＜ 0.001) were independent risk factors affecting daily living and working function. CONCLUSION: Most adult patients suffered with multiple affected joints in both upper and lower limbs. The elbow, hand and knee were the most frequently and severely affected joints. The pain and limited ROM were the independent risk factors of daily living and working function.

[Analysis of the differences in the characteristics of mesenchymal stem cells derived from jaw and long bones based on single-cell RNA-sequencing].

Objective: To study the whole bone marrow cellular composition of jaw and long bones, and further analyze the heterogeneity of mesenchymal stem cells (MSCs) derived from these two tissue, aiming at exploring the differences in functional characteristics of bone MSCs from different lineage sources. Methods: The Seurat package of R language was used to analyze the mandibular and femur whole bone marrow single-cell RNA-sequencing (scRNA-seq) datasets in the literature, and the subpopulations were annotated by reference to the marker genes reported by previous studies. The differentially expressed genes between mandible-derived MSCs (M-MSCs) and femur-derived MSCs (F-MSCs) were calculated, and cell-cell communication analysis between M-MSCs or F-MSCs with other cell populations was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on up-regulated and down-regulated differentially expressed genes of M-MSCs, and Gene Set Enrichment Analysis (GSEA) was performed on M-MSCs or F-MSCs. Results: cRNA-seq analysis showed that the mandible and femur had the same bone marrow cell composition, but there were differences in the proportion of specific cell populations. Also, there were significantly differentially expressed genes between M-MSCs and F-MSCs. In addition, cell-cell communication analysis revealed differences in numbers of ligand-receptor pairs between M-MSCs or F-MSCs with other cell populations. Furthermore, GO, KEGG and GSEA analysis showed that M-MSCs had higher extracellular matrix production potential than F-MSCs, but had lower ability to regulate other cells in the bone marrow, especially immune cells. Conclusions: M-MSCs and F-MSCs showed distinct differences in the gene expression pattern and up-regulated signaling pathways, which may be closely related to the developmental sources and functional characteristics of jaw and long bones.

Empowerment and its effects on clinical nurses in central China.

BACKGROUND: Chinese healthcare institutions have undergone constant changes in recent years. A large number of research studies conducted on work-related factors revealed that nurses in China experienced a low level of job satisfaction and a high level of turnover intention. Empowerment is one of the most important concepts in nursing and is most relevant to the study of nursing professionals' job-related outcomes. AIM: The aim of this study was to test the Job Characteristics Model and the mediating role of structural empowerment on the relationships between the job characteristics and work-related outcomes among clinical nurses from central China. METHODS: Three self-reported questionnaires were administered to a sample of 238 clinical nurses from two hospitals in central China. The results were analyzed using descriptive statistics, Pearson's correlation analysis and multiple linear regressions. FINDINGS: Correlations were significant between job characteristics and job-related outcomes, and the estimated model on the effect of empowerment reduced the unique contribution of job characteristics on internal work motivation (from 17.2% to 13.0%) and general job satisfaction (from 13.4% to 10.1%), and eliminated the unique contribution of job characteristics on growth satisfaction (from 18.4% to 0%). CONCLUSIONS: The results supported the Job Characteristics Model in a nursing sample and empowerment mediated the impact of job characteristics on internal work motivation and general job satisfaction partially and on growth satisfaction completely.

No high Tibetan Plateau until the Neogene.

The Late Paleogene surface height and paleoenvironment for the core area of the Qinghai-Tibetan Plateau (QTP) remain critically unresolved. Here, we report the discovery of the youngest well-preserved fossil palm leaves from Tibet. They were recovered from the Late Paleogene (Chattian), ca. 25.5 ± 0.5 million years, paleolake sediments within the Lunpola Basin (32.033°N, 89.767°E), central QTP at a present elevation of 4655 m. The anatomy of palms renders them intrinsically susceptible to freezing, imposing upper bounds on their latitudinal and altitudinal distribution. Combined with model-determined paleoterrestrial lapse rates, this shows that a high plateau cannot have existed in the core of Tibet in the Paleogene. Instead, a deep paleovalley, whose floor was <2.3 km above mean sea level bounded by (>4 km) high mountain systems, formed a topographically highly varied landscape. This finding challenges prevailing views on tectonic processes, monsoon dynamics, and the evolution of Asian biodiversity.

The antifibrinolytic and anti-inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial.

Essentials Perioperative blood loss and inflammatory response can significantly affect recovery after surgery. We studied the effects of multiple-dose oral tranexamic acid on blood loss and inflammatory response. A postoperative four-dose regimen brought about maximum reduction in postoperative blood loss. A postoperative four-dose regimen reduced inflammatory response and promoted early rehabilitation. SUMMARY: Background Tranexamic acid (TXA) can reduce blood loss and the inflammatory response at multiple doses in total knee arthroplasty patients. However, the optimal regimen has not been determined. Objectives To identify the most effective regimen for achieving maximum reductions in blood loss and the inflammatory response. Patients/Methods Two hundred and seventy-five patients were randomized to receive a placebo (group A), a single 2-g oral dose of TXA 2 h preoperatively followed by 1 g of oral TXA 3 h postoperatively (group B), a single dose followed by 1 g of oral TXA 3 h and 7 h postoperatively (group C), a single dose followed by 1 g of oral TXA 3 h, 7 h and 11 h postoperatively (group D), or a single dose followed by 1 g of oral TXA 3 h, 7 h, 11 h and 15 h postoperatively (group E). The primary outcome was total blood loss on postoperative day (POD) 3. Secondary outcomes included a decrease in the hemoglobin level, coagulation parameters, inflammatory marker levels, and thromboembolic complications. Results Groups D and E had significantly lower blood loss and smaller decreases in hemoglobin level than groups A, B, and C, with no significant difference on POD 3 between groups D and E. Significantly enhanced coagulation was identified for the four multiple-dose regimens; however, all thromboelastographic parameters remained within normal ranges. Group E had the lowest inflammatory marker levels and pain, and the greatest range of motion. No thromboembolic complications were identified. Conclusion The four-dose regimen yielded the maximum reductions in blood loss and inflammatory response, improved analgesia, and promoted early rehabilitation. Further studies are required to ensure that these findings are reproducible.

Blood-conserving efficacy of multiple doses of oral tranexamic acid associated with an enhanced-recovery programme in primary total knee arthroplasty: a randomized controlled trial.

Aims: The aim of this study was to identify the most effective regimen of multiple doses of oral tranexamic acid (TXA) in achieving maximum reduction of blood loss in total knee arthroplasty (TKA). Patients and Methods: In this randomized controlled trial, 200 patients were randomized to receive a single dose of 2.0 g of TXA orally two hours preoperatively (group A), a single dose of TXA followed by 1.0 g orally three hours postoperatively (group B), a single dose of TXA followed by 1.0 g three and nine hours postoperatively (group C), or a single dose of TXA followed by 1.0 g orally three, nine, and 15 hours postoperatively (group D). All patients followed a routine enhanced-recovery protocol. The primary outcome measure was the total blood loss. Secondary outcome measures were hidden blood loss (HBL), reduction in the level of haemoglobin, the rate of transfusion and adverse events. Results: Groups C (661.1 ml, sd 262.4) and D (597.7 ml, sd 219.6) had significantly lower mean total blood loss compared with groups A and B. The mean HBL was significantly lower in groups B (699.2 ml), C (533.1 ml) and D (469.9 ml) than in group A (p = 0.006, p < 0.001, and p < 0.001, respectively). Groups C (2.22 ml, sd 0.91) and D (2.04 ml, sd 0.95) had a lower reduction in the level of haemoglobin than groups A and B. However, there were no differences between groups C and D in relation to the three parameters. Conclusion: The addition of two or three postoperative doses of TXA to one preoperative dose produced a significant reduction in blood loss. The two-dose postoperative regimen is the least necessary regimen for clinical efficacy in primary unilateral TKA. The three-dose regimen produced maximum reduction of blood loss. Cite this article: Bone Joint J 2018;100-B:1025-32.

Inhibition of Nkcc1 promotes axonal growth and motor recovery in ischemic rats.

Bumetanide is a selective inhibitor of the Na+-K+-Cl--co-transporter 1(NKCC1). We studied whether bumetanide could affect axonal growth and behavioral outcome in stroke rats. Adult male Wistar rats were randomly assigned to four groups: sham-operated rats treated with vehicle or bumetanide, and ischemic rats treated with vehicle or bumetanide. Endothelin-1 was used to induce focal cerebral ischemia. Bumetanide administration (i.c.v.) started on postoperative day 7 and continued for 3 weeks. Biotinylated dextran amine (BDA) was injected into the right imotor cortex on postoperative day 14 to trace corticospinal tract (CST) fibers sprouting into the denervated cervical spinal cord. Nogo-A, NKCC1, KCC2 and BDNF in the perilesional cortex and BDA, PSD-95 and vGlut1 in the denervated spinal cord were measured by immunohistochemistry and/or Western blot. Behavioral outcome of rats was assessed by the beam walking and cylinder tests. The total length of CST fibers sprouting into the denervated cervical spinal cord significantly increased after stroke and bumetanide further increased this sprouting. Bumetanide treatment also decreased the expressions of NKCC1 and Nogo-A, increased the expressions of KCC2 and BDNF in the perilesional cortex and enhanced the synaptic plasticity in the denervated cervical spinal cord after cerebral ischemia. The behavioral performance of ischemic rats was significantly improved by bumetanide. In conclusion, bumetanide promoted post-stroke axonal sprouting together accompanied by an improved behavioral outcome possibly through restoring and maintaining neuronal chloride homeostasis and creating a recovery-promoting microenvironment by overcoming the axonal growth inhibition encountered after cerebral ischemia in rats.

Dissociation and aggregation of D-glyceraldehyde-3-phosphate dehydrogenase during denaturation by guanidine hydrochloride.

The inactivation of lobster muscle D-glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) (GAPDH) during guanidine hydrochloride (GdnHCl) denaturation has been compared with its state of aggregation and unfolding, by light scattering and fluorescence measurements. The enzyme first dissociates at low concentrations of GdnHCl, followed by the formation of a highly aggregated state with increasing denaturant concentrations, and eventually by complete unfolding and dissociation to the monomer at concentrations of greater than 2 M GdnHCl. The aggregation and final dissociation correspond roughly with the two stages of fluorescence changes reported previously (Xie, G.-F. and Tsou, C.-L. (1987) Biochim. Biophys. Acta 911, 19-24). Rate measurements show a very rapid inactivation, the extents of which increase with increasing concentrations of GdnHCl. This initial rapid phase of inactivation which takes place before dissociation and unfolding of the molecule is in agreement with the results obtained with other enzymes, that the active site is affected before noticeable conformational changes can be detected for the enzyme molecule as a whole. A scheme for the steps leading to the final denaturation, and dissociation of the enzyme to the inactive and unfolded monomer, is proposed.

Comparison of inactivation and conformational changes of D-glyceraldehyde-3-phosphate dehydrogenase during thermal denaturation.

The inactivation of D-glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating) EC 1.2.1.12) (GAPDH) during thermal denaturation has been compared to its dissociation-aggregation measured by light scattering and changes in secondary structure measured by CD in the far ultraviolet. The inactivation at 38.5 degrees C consists of two stages. The rate of the first stage is too fast to be followed by conventional methods. The extent of this fast stage inactivation increases with increasing temperature and, more markedly, with increasing pH. At this stage, the inactivation is reversible and no appreciable dissociation or change in secondary structure can be detected. The secondary structure of the enzyme is relatively heat stable, showing no appreciable change at 38.5 degrees C. At this temperature, the enzyme first dissociates within several minutes probably into dimers and with prolonged heating, it becomes irreversibly aggregated. The above results are in accord with the earlier suggestion, based on results obtained during denaturation of a number of enzymes by guanidine hydrochloride (GdnHCl) and urea, that for some enzymes the active site is situated in a region more susceptible to perturbation than the molecule as a whole (Tsou, C.-L. (1986) Trends Biochem. Sci. 11, 427).

Is there reduced polyethylene wear and longer survival when using a mobile-bearing design in total knee replacement? A meta-analysis of randomised and non-randomised controlled trials.

The purpose of this study was to undertake a meta-analysis to determine whether there is lower polyethylene wear and longer survival when using mobile-bearing implants in total knee replacement when compared with fixed-bearing implants. Of 975 papers identified, 34 trials were eligible for data extraction and meta-analysis comprising 4754 patients (6861 knees). We found no statistically significant differences between the two designs in terms of the incidence of radiolucent lines, osteolysis, aseptic loosening or survival. There is thus currently no evidence to suggest that the use of mobile-bearing designs reduce polyethylene wear and prolong survival after total knee replacement.