Evolutionary Selection and Constraint on Human Knee Chondrocyte Regulation Impacts Osteoarthritis Risk.

During human evolution, the knee adapted to the biomechanical demands of bipedalism by altering chondrocyte developmental programs. This adaptive process was likely not without deleterious consequences to health. Today, osteoarthritis occurs in 250 million people, with risk variants enriched in non-coding sequences near chondrocyte genes, loci that likely became optimized during knee evolution. We explore this relationship by epigenetically profiling joint chondrocytes, revealing ancient selection and recent constraint and drift on knee regulatory elements, which also overlap osteoarthritis variants that contribute to disease heritability by tending to modify constrained functional sequence. We propose a model whereby genetic violations to regulatory constraint, tolerated during knee development, lead to adult pathology. In support, we discover a causal enhancer variant (rs6060369) present in billions of people at a risk locus (GDF5-UQCC1), showing how it impacts mouse knee-shape and osteoarthritis. Overall, our methods link an evolutionarily novel aspect of human anatomy to its pathogenesis.

Drug-drug interaction prediction with learnable size-adaptive molecular substructures.

Drug-drug interactions (DDIs) are interactions with adverse effects on the body, manifested when two or more incompatible drugs are taken together. They can be caused by the chemical compositions of the drugs involved. We introduce gated message passing neural network (GMPNN), a message passing neural network which learns chemical substructures with different sizes and shapes from the molecular graph representations of drugs for DDI prediction between a pair of drugs. In GMPNN, edges are considered as gates which control the flow of message passing, and therefore delimiting the substructures in a learnable way. The final DDI prediction between a drug pair is based on the interactions between pairs of their (learned) substructures, each pair weighted by a relevance score to the final DDI prediction output. Our proposed method GMPNN-CS (i.e. GMPNN + prediction module) is evaluated on two real-world datasets, with competitive results on one, and improved performance on the other compared with previous methods. Source code is freely available at https://github.com/kanz76/GMPNN-CS.

Predict multi-type drug-drug interactions in cold start scenario.

BACKGROUND: Prediction of drug-drug interactions (DDIs) can reveal potential adverse pharmacological reactions between drugs in co-medication. Various methods have been proposed to address this issue. Most of them focus on the traditional link prediction between drugs, however, they ignore the cold-start scenario, which requires the prediction between known drugs having approved DDIs and new drugs having no DDI. Moreover, they're restricted to infer whether DDIs occur, but are not able to deduce diverse DDI types, which are important in clinics. RESULTS: In this paper, we propose a cold start prediction model for both single-type and multiple-type drug-drug interactions, referred to as CSMDDI. CSMDDI predict not only whether two drugs trigger pharmacological reactions but also what reaction types they induce in the cold start scenario. We implement several embedding methods in CSMDDI, including SVD, GAE, TransE, RESCAL and compare it with the state-of-the-art multi-type DDI prediction method DeepDDI and DDIMDL to verify the performance. The comparison shows that CSMDDI achieves a good performance of DDI prediction in the case of both the occurrence prediction and the multi-type reaction prediction in cold start scenario. CONCLUSIONS: Our approach is able to predict not only conventional binary DDIs but also what reaction types they induce in the cold start scenario. More importantly, it learns a mapping function who can bridge the drugs attributes to their network embeddings to predict DDIs. The main contribution of CSMDDI contains the development of a generalized framework to predict the single-type and multi-type of DDIs in the cold start scenario, as well as the implementations of several embedding models for both single-type and multi-type of DDIs. The dataset and source code can be accessed at https://github.com/itsosy/csmddi .

Stage-specific influence of temperature on the growth rate of Japanese Spanish mackerel (Scomberomorus niphonius) in early life.

Since 1850, each successive decade has been warmer than any preceding one. Warming could make a major contribution to the growth of fish larvae. To evaluate the influence of water temperature on the growth of larvae who spawned in later spring and early summer, we selected Scomberomorus niphonius, which has important ecological and economic value as a sample fish species. We conducted high-resolution spatiotemporal surveys during the 2015 spawning season at an important spawning ground in China. We found that the temperature required for larval survival was stricter than that for spawning. Within the appropriate temperature range, a rapid rise in water temperature was favourable for larval hatching, but S. niphonius hatched at relatively low temperature exhibited a faster growth rate in the yolk-sac and pre-flexion stages. The accumulated temperature and hatching temperature significantly affected the growth rate of S. niphonius larvae. The model that considered developmental stages provided a better explanation of the data than the model that only considered the temperature effect. The model improvement in terms of variance explained was higher for the early developmental stages than for the later developmental stages, suggesting that stage-specific temperature influences were prominent in the earlier stages, like the yolk-sac stage, and then reduced. Our results implied that water temperature anomalies could be hazardous to fish larvae, especially for fish spawning in late spring and early summer. Given that early-life stage fish are highly sensitive to water temperature, it is imperative to incorporate the potential effects of climate change into fisheries management.

Large G protein α-subunit XLαs limits clathrin-mediated endocytosis and regulates tissue iron levels in vivo.

Alterations in the activity/levels of the extralarge G protein α-subunit (XLαs) are implicated in various human disorders, such as perinatal growth retardation. Encoded by GNAS, XLαs is partly identical to the α-subunit of the stimulatory G protein (Gsα), but the cellular actions of XLαs remain poorly defined. Following an initial proteomic screen, we identified sorting nexin-9 (SNX9) and dynamins, key components of clathrin-mediated endocytosis, as binding partners of XLαs. Overexpression of XLαs in HEK293 cells inhibited internalization of transferrin, a process that depends on clathrin-mediated endocytosis, while its ablation by CRISPR/Cas9 in an osteocyte-like cell line (Ocy454) enhanced it. Similarly, primary cardiomyocytes derived from XLαs knockout (XLKO) pups showed enhanced transferrin internalization. Early postnatal XLKO mice showed a significantly higher degree of cardiac iron uptake than wild-type littermates following iron dextran injection. In XLKO neonates, iron and ferritin levels were elevated in heart and skeletal muscle, where XLαs is normally expressed abundantly. XLKO heart and skeletal muscle, as well as XLKO Ocy454 cells, showed elevated SNX9 protein levels, and siRNA-mediated knockdown of SNX9 in XLKO Ocy454 cells prevented enhanced transferrin internalization. In transfected cells, XLαs also inhibited internalization of the parathyroid hormone and type 2 vasopressin receptors. Internalization of transferrin and these G protein-coupled receptors was also inhibited in cells expressing an XLαs mutant missing the Gα portion, but not Gsα or an N-terminally truncated XLαs mutant unable to interact with SNX9 or dynamin. Thus, XLαs restricts clathrin-mediated endocytosis and plays a critical role in iron/transferrin uptake in vivo.

Summary of respiratory rehabilitation and physical therapy guidelines for patients with COVID-19 based on recommendations of World Confederation for Physical Therapy and National Association of Physical Therapy.

[Purpose] To summarize the existing official guidelines issued by the World Confederation for Physical Therapy and Associations of Physical Therapy in various countries and to clarify the recommended methods of respiratory rehabilitation and physiotherapy for patients in different stages of the coronavirus disease of 2019 (COVID-19). [Methods] An introductory literature search was conducted using the keywords "COVID-19", "respiratory rehabilitation", "physical therapy", and others in the database of the Association of Physical Therapy. [Results] Using 12 coronavirus disease-2019 rehabilitation-related articles, we summarized data on physical therapy (PT) evaluation; treatment; indications; contraindications; and termination indicators for patients in acute, stable, and post-discharge stages. [Conclusion] PT for COVID-19 patients with coronavirus disease 2019 should be formulated according to the stage of the disease and condition of the patients.

Myeloid ß-Catenin Deficiency Exacerbates Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice.

OBJECTIVE: The Wnt/ß-catenin signaling is an ancient and evolutionarily conserved pathway that regulates essential aspects of cell differentiation, proliferation, migration and polarity. Canonical Wnt/ß-catenin signaling has also been implicated in the pathogenesis of atherosclerosis. Macrophage is one of the major cell types involved in the initiation and progression of atherosclerosis, but the role of macrophage ß-catenin in atherosclerosis remains elusive. This study aims to investigate the impact of ß-catenin expression on macrophage functions and atherosclerosis development. APPROACH AND RESULTS: To investigate the role of macrophage canonical Wnt/ß-catenin signaling in atherogenesis, we generated ß-cateninΔmyeLDLR-/- mice (low-density lipoprotein receptor-deficient mice with myeloid-specific ß-catenin deficiency). As expected, deletion of ß-catenin decreased macrophage adhesion and migration properties in vitro. However, deficiency of ß-catenin significantly increased atherosclerotic lesion areas in the aortic root of LDLR-/- (low-density lipoprotein receptor-deficient) mice without affecting the plasma lipid levels and atherosclerotic plaque composition. Mechanistic studies revealed that ß-catenin can regulate activation of STAT (signal transducer and activator of transcription) pathway in macrophages, and ablation of ß-catenin resulted in STAT3 downregulation and STAT1 activation, leading to elevated macrophage inflammatory responses and increased atherosclerosis. CONCLUSIONS: This study demonstrates a critical role of myeloid ß-catenin expression in atherosclerosis by modulating macrophage inflammatory responses.

Impact of broad regulatory regions on Gdf5 expression and function in knee development and susceptibility to osteoarthritis.

OBJECTIVES: Given the role of growth and differentiation factor 5 (GDF5) in knee development and osteoarthritis risk, we sought to characterise knee defects resulting from Gdf5 loss of function and how its regulatory regions control knee formation and morphology. METHODS: The brachypodism (bp) mouse line, which harbours an inactivating mutation in Gdf5, was used to survey how Gdf5 loss of function impacts knee morphology, while two transgenic Gdf5 reporter bacterial artificial chromosome mouse lines were used to assess the spatiotemporal activity and function of Gdf5 regulatory sequences in the context of clinically relevant knee anatomical features. RESULTS: Knees from homozygous bp mice (bp/bp) exhibit underdeveloped femoral condyles and tibial plateaus, no cruciate ligaments, and poorly developed menisci. Secondary ossification is also delayed in the distal femur and proximal tibia. bp/bp mice have significantly narrower femoral condyles, femoral notches and tibial plateaus, and curvier medial femoral condyles, shallower trochlea, steeper lateral tibial slopes and smaller tibial spines. Regulatory sequences upstream from Gdf5 were weakly active in the prenatal knee, while downstream regulatory sequences were active throughout life. Importantly, downstream but not upstream Gdf5 regulatory sequences fully restored all the key morphological features disrupted in the bp/bp mice. CONCLUSIONS: Knee morphology is profoundly affected by Gdf5 absence, and downstream regulatory sequences mediate its effects by controlling Gdf5 expression in knee tissues. This downstream region contains numerous enhancers harbouring human variants that span the osteoarthritis association interval. We posit that subtle alterations to morphology driven by changes in downstream regulatory sequence underlie this locus' role in osteoarthritis risk.

High resolution magnetic resonance imaging in pathogenesis diagnosis of single lenticulostriate infarction with nonstenotic middle cerebral artery, a retrospective study.

BACKGROUND: It is usually difficult to identify stroke pathogenesis for single lenticulostriate infarction with nonstenotic middle cerebral artery (MCA). Our aim is to differentiate the two pathogeneses, non-branch atheromatous small vessel disease and branch atheromatous disease (BAD) by high-resolution magnetic resonance imaging (HR-MRI). METHODS: Thirty-two single lenticulostriate infarction patients with nonstenotic MCA admitted to the China-Japan Friendship Hospital from December 2014 to August 2017 were enrolled for retrospective analysis. National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), atherosclerotic risk factors, imaging features, and the characteristic of MCA vessel wall in HR-MRI were evaluated. RESULTS: MCA plaques were detected in 15(46.9%) patients which implied BAD and 8 of 15 (53.3%) patients had plaques location in upper dorsal side of the vessel wall. Patients with HR-MRI identified plaques had a significantly larger infarction lesion length (1.95 ± 0.86 cm versus 1.38 ± 0.55 cm; P = 0.031) and larger lesion volume (2.95 ± 3.94 cm3 versus 0.90 ± 0.94 cm3; P = 0.027) than patients without plaques. Patients with HR-MRI identified plaques had a significant higher percentage of proximal lesions than patients without plaques (P = 0.055). However, according to the location of MCA plaques, there were no significant differences in terms of imaging features, NIHSS and mRS. CONCLUSION: We demonstrated high frequency of MCA atheromatous plaques visualized in single lenticulostriate infarction patients with nonstenotic MCA by using HR-MRI. Patients with HR-MRI identified plaque presented larger infarction lesions and more proximal lesions than patients without plaque, which were consistent with imaging features of BAD. HR-MRI is an important and effective tool for identifying stroke etiology in patients with nonstenotic MCA.

Targeting IκB kinase ß in Adipocyte Lineage Cells for Treatment of Obesity and Metabolic Dysfunctions.

IκB kinase ß (IKKß), a central coordinator of inflammation through activation of nuclear factor-κB, has been identified as a potential therapeutic target for the treatment of obesity-associated metabolic dysfunctions. In this study, we evaluated an antisense oligonucleotide (ASO) inhibitor of IKKß and found that IKKß ASO ameliorated diet-induced metabolic dysfunctions in mice. Interestingly, IKKß ASO also inhibited adipocyte differentiation and reduced adiposity in high-fat (HF)-fed mice, indicating an important role of IKKß signaling in the regulation of adipocyte differentiation. Indeed, CRISPR/Cas9-mediated genomic deletion of IKKß in 3T3-L1 preadipocytes blocked these cells differentiating into adipocytes. To further elucidate the role of adipose progenitor IKKß signaling in diet-induced obesity, we generated mice that selectively lack IKKß in the white adipose lineage and confirmed the essential role of IKKß in mediating adipocyte differentiation in vivo. Deficiency of IKKß decreased HF-elicited adipogenesis in addition to reducing inflammation and protected mice from diet-induced obesity and insulin resistance. Further, pharmacological inhibition of IKKß also blocked human adipose stem cell differentiation. Our findings establish IKKß as a pivotal regulator of adipogenesis and suggest that overnutrition-mediated IKKß activation serves as an initial signal that triggers adipose progenitor cell differentiation in response to HF feeding. Inhibition of IKKß with antisense therapy may represent as a novel therapeutic approach to combat obesity and metabolic dysfunctions. Stem Cells 2016;34:1883-1895.

CT- versus MRI-based patient-specific instrumentation for total knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: To determine whether computed tomography (CT) or magnetic resonance imaging (MRI) is more suitable for the patient-specific instrumentation (PSI) systems for total knee arthroplasty (TKA). METHODS: PubMed, Embase, and the Cochrane Library were searched from inception to June 2016 for prospective comparative trials that compared CT- versus MRI-based PSI systems for TKA. Our predefined primary outcome was the outliers incidence of coronal overall limb alignment. RESULTS: Six studies with a total of 336 knees meeting the eligibility criteria, and four trials were included in the meta-analysis. Compared with MRI-based PSI systems, CT-based PSI systems were associated with a higher outliers incidence of coronal overall limb alignment (risk ratio: 1.67; 95% confidence interval (CI): 1.03-2.72; P = 0.04), more angular errors of coronal overall limb alignment (mean difference (MD): 1.01°; 95% CI: 0.47-1.56; P = 0.0003), and longer operation time (MD: 5.02 min; 95% CI: 1.26-8.79; P = 0.009). While no significant differences in the coronal/sagittal alignment of the femoral/tibial component outliers, the angular errors of coronal overall limb alignment, the angular errors of the femoral/tibial component in coronal plane, or incidence of change of implant size of the femoral/tibial component were observed. CONCLUSIONS: The current limited evidence suggests that MRI-based PSI systems exhibit higher accuracy for TKA regarding the coronal limb axis than CT-based PSI systems. However, well-designed studies comparing CT-versus MRI-based PSI systems for TKA are warrant to confirm these results before widespread use of this technique can be recommended.

Etanercept alleviates early brain injury following experimental subarachnoid hemorrhage and the possible role of tumor necrosis factor-α and c-Jun N-terminal kinase pathway.

Cerebral inflammation plays a crucial role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). This study investigated the effects of c-Jun N-terminal kinase (JNK) inhibitor SP600125, acetylcholine (Ach), etanercept, and anti-TNF-α on cellular apoptosis in the cerebral cortex and the hippocampus, in order to establish the role of JNK and TNF-α in EBI. The SAH model was established using an endovascular puncture protocol. The reliability of the EBI model was determined by phosphorylated-Bad (pBad) immunohistochemistry. Neurological scores were recorded and western blot was used to detect the expression of JNK and TNF-α, and TUNEL assay was used to mark apoptotic cells. The results showed that pBad positive cells were evenly distributed in the cerebral cortex at different time points. The highest expression of pBad was reached 1 day after SAH, and pJNK and TNF-α reached their peak expression at 2 days after SAH. SP600125, Ach, and etanercept significantly decreased the level of pJNK and TNF-α in the cerebral cortex and the hippocampus. In addition, SP600125 and etanercept reduced cellular apoptosis in the cerebral cortex and the hippocampus and significantly improved neurological scores at 2 days after SAH potentially via inhibition of the JNK-TNF-α pathway. Ach reduced cellular apoptosis only in the cerebral cortex. It is possible that JNK induces TNF-α expression, which in turn enhances JNK expression in EBI after SAH, leading to increased apoptosis in the cerebral cortex and the hippocampus. Thus, our results indicate that that etanercept may be a potential therapeutic agent to alleviate EBI.

Curcumin protects neurons against oxygen-glucose deprivation/reoxygenation-induced injury through activation of peroxisome proliferator-activated receptor-γ function.

The turmeric derivative curcumin protects against cerebral ischemic injury. We previously demonstrated that curcumin activates peroxisome proliferator-activated receptor-γ (PPARγ), a ligand-activated transcription factor involved in both neuroprotective and anti-inflammatory signaling pathways. This study tested whether the neuroprotective effects of curcumin against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury of rat cortical neurons are mediated (at least in part) by PPARγ. Curcumin (10 µM) potently enhanced PPARγ expression and transcriptional activity following OGD/R. In addition, curcumin markedly increased neuronal viability, as evidenced by decreased lactate dehydrogenase release and reduced nitric oxide production, caspase-3 activity, and apoptosis. These protective effects were suppressed by coadministration of the PPARγ antagonist 2-chloro-5-nitrobenzanilide (GW9662) and by prior transfection of a small-interfering RNA (siRNA) targeting PPARγ, treatments that had no toxic effects on healthy neurons. Curcumin reduced OGD/R-induced accumulation of reactive oxygen species and inhibited the mitochondrial apoptosis pathway, as indicated by reduced release of cytochrome c and apoptosis-inducing factor and maintenance of both the mitochondrial membrane potential and the Bax/Bcl-2 ratio. Again, GW9662 or PPARγ siRNA transfection mitigated the protective effects of curcumin on mitochondrial function. Curcumin suppressed IκB kinase phosphorylation and IκB degradation, thereby inhibiting nuclear factor-κ B (NF-κB) nuclear translocation, effects also blocked by GW9662 or PPARγ siRNA. Immunoprecipitation experiments revealed that PPARγ interacted with NF-κB p65 and inhibited NF-κB activation. The present study provides strong evidence that at least some of the neuroprotective effects of curcumin against OGD/R are mediated by PPARγ activation.

Prediction of drug-target binding affinity based on multi-scale feature fusion.

Accurate prediction of drug-target binding affinity (DTA) plays a pivotal role in drug discovery and repositioning. Although deep learning methods are widely used in DTA prediction, two significant challenges persist: (i) how to effectively represent the complex structural information of proteins and drugs; (ii) how to precisely model the mutual interactions between protein binding sites and key drug substructures. To address these challenges, we propose a MSFFDTA (Multi-scale feature fusion for predicting drug target affinity) model, in which multi-scale encoders effectively capture multi-level structural information of drugs and proteins are designed. And then a Selective Cross Attention (SCA) mechanism is developed to filter out the trivial interactions between drug-protein substructure pairs and retain the important ones, which will make the proposed model better focusing on these key interactions and offering insights into their underlying mechanism. Experimental results on two benchmark datasets demonstrate that MSFFDTA is superior to several state-of-the-art methods across almost all comparison metrics. Finally, we provide the ablation and case studies with visualizations to verify the effectiveness and the interpretability of MSFFDTA. The source code is freely available at https://github.com/whitehat32/MSFF-DTA/.

The effect of preoperative different dexamethasone regimens on postoperative glycemic control in patients with type 2 diabetes mellitus undergoing total joint arthroplasty: a retrospective cohort study.

BACKGROUND: Concerns have been raised regarding the impact of preoperative intravenous dexamethasone on postoperative glycemic control in diabetic patients undergoing total joint arthroplasty (TJA). This study aimed to determine relationships between preoperative different dexamethasone regimens and postoperative fasting blood glucose (FBG), as well as to identify risk factors for postoperative FBG ≥ 200 mg/dl in diabetic patients undergoing TJA. METHODS: This retrospective study included 1216 diabetic patients undergoing TJA and categorized into group A (dexamethasone = 0 mg), group B (dexamethasone = 5 mg), and group C (dexamethasone = 10 mg). All dexamethasone was administered before skin incision. FBG levels were monitored until postoperative day (POD) 3. Analyses were conducted for periprosthetic joint infection (PJI) and wound complications during 90 days postoperatively. And the risk factors for postoperative FBG ≥ 200 mg/dl were identified. RESULTS: Preoperative dexamethasone administration resulted in a transiently higher FBG on POD 0 and POD 1 (all P < 0.001). However, no differences were observed on POD 2 (P = 0.583) and POD 3 (P = 0.131) among three groups. While preoperative dexamethasone led to an increase in postoperative mean FBG and postoperative maximum FBG (all P < 0.001), no differences were found in wound complications (P = 0.548) and PJI (P = 1.000). Increased HbA1c and preoperative high FBG, but not preoperative dexamethasone, were identified as risk factors for postoperative FBG ≥ 200 mg/dl. Preoperative HbA1c level of ≥ 7.15% was associated with an elevated risk of postoperative FBG ≥ 200 mg/dl. CONCLUSIONS: Although preoperative intravenous administration of 5 mg or 10 mg dexamethasone in diabetic patients showed transient effects on postoperative FBG after TJA, no differences were found in the rates of PJI and wound complications during 90 days postoperatively. Notably, patients with a preoperative HbA1c level of ≥ 7.15% and elevated preoperative FBG may encountered postoperative FBG ≥ 200 mg/dl.

PNPO-PLP axis senses prolonged hypoxia in macrophages by regulating lysosomal activity.

Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen-sensing systems inducing acute hypoxic responses, including the hypoxia-inducible factor pathway, have been identified, those operating in prolonged hypoxia remain to be elucidated. Here we show that pyridoxine 5'-phosphate oxidase (PNPO), which catalyses bioactivation of vitamin B6, serves as an oxygen sensor and regulates lysosomal activity in macrophages. Decreased PNPO activity under prolonged hypoxia reduced an active form of vitamin B6, pyridoxal 5'-phosphate (PLP), and inhibited lysosomal acidification, which in macrophages led to iron dysregulation, TET2 protein loss and delayed resolution of the inflammatory response. Among PLP-dependent metabolism, supersulfide synthesis was suppressed in prolonged hypoxia, resulting in the lysosomal inhibition and consequent proinflammatory phenotypes of macrophages. The PNPO-PLP axis creates a distinct layer of oxygen sensing that gradually shuts down PLP-dependent metabolism in response to prolonged oxygen deprivation.

Molecular characteristics of Neisseria meningitidis isolated during an outbreak in a jail: association with the spread and distribution of ST-4821 complex serogroup C clone in China.

OBJECTIVE: To characterize the meningococcal strains isolated from cases and close contacts with meningococcal disease associated with an outbreak in a jail in May 2010 by investigating the national distribution of hyperinvasive ST-4821 serogroup C clone associated with this outbreak. METHODS: The cases were described based on the clinical symptoms and laboratory results. Pharyngeal swabs were cultured for N. meningitidis from men in the jail. Meningococcal isolates were identified by serogrouping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST), respectively. Four hundred and sixteen serogroup C N. meningitidis strains were collected from 27 provinces between 2003 and 2010 for a nationwide survey and analyzed by PFGE and MLST. RESULTS: Three persons in a jail system were infected with invasive N. meningitidis serogroup C. All isolates tested had matching PFGE patterns and belonged to the multilocus sequence type (ST) 4821 clonal complex. All 47 N. meningitidis strains were identified from the pharyngeal swabs of 166 peoples in the jail, and 26 of them belonged to ST-4821 serogroup C clone, and 90.14% (375/416) serogroup C strains identified in the nationwide survey belonged to the ST-4821 complex. The ST-4821 serogroup C clone was spread nationwide, distributed in 24 provinces, especially in eastern provinces between 2003 and 2010. CONCLUSION: Endemic transmission and carriage rate of ST-4821 serogroup C clone are high in this jail system. The ST-4821 serogroup C clone is spreading in China and nationwide distributed despite the existence of some effective vaccines.

Spatial evolution of global petrochemical risk and the influence by industrialization.

The petrochemical industry is an integral contributor to the global economy and plays a critical role in improving the lives of people worldwide. However, its development has also led to frequent accidents, and the evolution and global impact of these risks have not been adequately assessed. This study is aimed at quantitatively analyzing the current state of petrochemical risk and its impact on industrial development in 58 coastal countries (regions) worldwide by identifying petrochemical risk impact indicators and constructing threshold regression models. We showed that the global petrochemical risk has been unevenly decreasing in recent years. In some countries (regions), the petrochemical risk remains unchanged or is increasing; in particular, coastal provinces of China need to address this issue. Moreover, when industrialization and economic development levels are < 53.6 and 34,918.4 USD/person, respectively, petrochemical accidents negatively affect industrial development; however, above these thresholds, they do not impact industrial development. Coastal areas of China and some developing countries are far below these thresholds. Therefore, the risk from petrochemicals remains a critical factor affecting industrial development in countries with low industrialization levels.

A Review of Strategies Associated with Surgical Decompression in Traumatic Spinal Cord Injury.

Traumatic spinal cord injury (TSCI) is frequent. Timely diagnosis and treatment have reduced the mortality, but the long-term recovery of neurologic functions remains ominous. After TSCI, tissue bleeding, edema, and adhesions lead to an increase in the intraspinal pressure, further causing the pathophysiologic processes of ischemia and hypoxia and eventually accelerating the cascade of secondary spinal cord injury. Timely surgery with appropriate decompression strategies can reduce that secondary injury. However, disagreement about the safety and effectiveness of decompression surgery and the timing of surgery still exists. The level and severity of spinal cord injury do have an impact on the timing of surgery; therefore, TSCI subpopulations may benefit from early surgery. Early surgery perhaps has little effect on recovery from complete TSCI but might be of benefit in patients with incomplete injury. Early decompression should be considered in patients with incomplete cervical TSCI. Patient age should not be used as an exclusion criterion for early surgery. The best time point for early surgery is although influenced by the shortest duration to thoroughly examine the patient's condition and stabilize the patient's state. After the patient's condition is fully evaluated, we can perform the surgical modality of emergency myelotomy and decompression. Therefore, a number of conditions should be considered, such as standardized decompression methods, indications and operation timing to ensure the effectiveness and safety of early surgical intervention, and promotion of the functional recovery of residual nerve tissue.

Bone wax reduces blood loss after total hip arthroplasty: a prospective, randomized controlled study.

Background: Previous studies have demonstrated the efficacy of bone wax in reducing blood loss in various orthopedic surgeries. However, the effect of bone wax on total hip arthroplasty (THA) remains unclear. The objective of this study was to assess the efficacy of bone wax in THA. Methods: We enrolled 104 patients in this randomized controlled trial. These patients were randomized (1:1) to either the bone wax or control group. The primary outcome was total blood loss after THA. The secondary outcomes included serum hemoglobin (Hb) level, change in Hb level, lower limb diameters on the first and third postoperative day (POD), range of motion at discharge, length of postoperative hospital stay, and adverse events. Results: Patients in the bone wax group had significantly lower total blood loss on PODs 1 and 3 (p < 0.05). Moreover, patients in the bone wax group performed better in terms of postoperative serum Hb level, change in Hb level on PODs 1 and 3, and length of postoperative hospital stay (all p < 0.05). Patients in the bone wax group did not experience any bone wax-related adverse events. Conclusion: Bone wax administration in THA significantly reduced perioperative blood loss. Therefore, bone wax is promising for optimizing blood-conserving management protocols in THA. Clinical trial registration: [https://clinicaltrials.gov/], identifier [ChiCTR2100043868].