Protective effects of human urinary kallidinogenase against corticospinal tract damage in acute ischemic stroke patients.

This study aimed to assess the effects of human urinary kallidinogenase (HUK) on motor function outcome and corticospinal tract recovery in patients with acute ischemic stroke (AIS). This study was a randomized, controlled, single-blinded trial. Eighty AIS patients were split into two groups: the HUK and control groups. The HUK group was administered HUK and standard treatment, while the control group received standard treatment only. At admission and discharge, the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI) and muscle strength were scored. The primary endpoint was the short-term outcomes of AIS patients under different treatments. The secondary endpoint was the degree of corticospinal tract fiber damage under different treatments. There was a significant improvement in the NIHSS Scale, BI and muscle strength scores in the HUK group compared with controls (Mann-Whitney U test; P  < 0.05). Diffusion tensor tractography classification and intracranial arterial stenosis were independent predictors of short-term recovery by linear regression analysis. The changes in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) decline rate were significantly smaller in the HUK group than in the control group ( P <  0.05). Vascular endothelial growth factor (VEGF) increased significantly after HUK treatment ( P  < 0.05), and the VEGF change was negatively correlated with changes in ADC. HUK is beneficial for the outcome in AIS patients especially in motor function recovery. It may have protective effects on the corticospinal tract which is reflected by the reduction in the FA and ADC decline rates and increased VEGF expression. The study was registered on ClinicalTrials.gov (unique identifier: NCT04102956).

Evaluation and Application of Silk Fibroin Based Biomaterials to Promote Cartilage Regeneration in Osteoarthritis Therapy.

Osteoarthritis (OA) is a common joint disease characterized by cartilage damage and degeneration. Traditional treatments such as NSAIDs and joint replacement surgery only relieve pain and do not achieve complete cartilage regeneration. Silk fibroin (SF) biomaterials are novel materials that have been widely studied and applied to cartilage regeneration. By mimicking the fibrous structure and biological activity of collagen, SF biomaterials can promote the proliferation and differentiation of chondrocytes and contribute to the formation of new cartilage tissue. In addition, SF biomaterials have good biocompatibility and biodegradability and can be gradually absorbed and metabolized by the human body. Studies in recent years have shown that SF biomaterials have great potential in treating OA and show good clinical efficacy. Therefore, SF biomaterials are expected to be an effective treatment option for promoting cartilage regeneration and repair in patients with OA. This article provides an overview of the biological characteristics of SF, its role in bone and cartilage injuries, and its prospects in clinical applications to provide new perspectives and references for the field of bone and cartilage repair.

The miR-21-5p enriched in the apoptotic bodies of M2 macrophage-derived extracellular vesicles alleviates osteoarthritis by changing macrophage phenotype.

Macrophages (Mφs) play a crucial role in the pathological progression of osteoarthritis (OA) by regulating inflammation and tissue repair. Decreasing pro-inflammatory M1-Mφs and increasing anti-inflammatory M2-Mφs can alleviate OA-related inflammation and promote cartilage repair. Apoptosis is a natural process associated with tissue repair. A large number of apoptotic bodies (ABs), a type of extracellular vesicle, are produced during apoptosis, and this is associated with a reduction in inflammation. However, the functions of apoptotic bodies remain largely unknown. In this study, we investigated the role of M2-Mφs-derived apoptotic bodies (M2-ABs) in regulating the M1/M2 balance of macrophages in a mouse model of OA. Our data show that M2-ABs can be targeted for uptake by M1-Mφs, and this reprograms M1-to-M2 phenotypes within 24 h. The M2-ABs significantly ameliorated the severity of OA, alleviated the M1-mediated pro-inflammatory environment, and inhibited chondrocyte apoptosis in mice. RNA-seq revealed that M2-ABs were enriched with miR-21-5p, a microRNA that is negatively correlated with articular cartilage degeneration. Inhibiting the function of miR-21-5p in M1-Mφs significantly reduced M2-ABs-guided M1-to-M2 reprogramming following in vitro cell transfection. Together, these results suggest that M2-derived apoptotic bodies can prevent articular cartilage damage and improve gait abnormalities in OA mice by reversing the inflammatory response caused by M1 macrophages. The mechanism underlying these findings may be related to miR-21-5p-regulated inhibition of inflammatory factors. The application of M2-ABs may represent a novel cell therapy, and could provide a valuable strategy for the treatment of OA and/or chronic inflammation.

Joint fluid interleukin-6 combined with the neutral polymorphonuclear leukocyte ratio (PMN%) as a diagnostic index for chronic periprosthesis infection after arthroplasty.

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) remains a challenge in clinical practice. Many novel serum and joint fluid biomarkers have important implications for the diagnosis of PJI. The presented study evaluated the value of joint fluid interleukin-6 (IL-6) combined with the neutral polymorphonuclear leukocyte (PMN%) ratio for chronic PJI diagnosis after arthroplasty. MATERIALS AND METHODS: Sixty patients with chronic PJI or aseptic failure who underwent hip or knee revision from January 2018 to January 2020 in our department were included in this retrospective study. According to the 2013 MSIS diagnostic criteria, the 60 patients were divided into a PJI group and a non-PJI group (30 patients per group). We collected the joint fluid before surgery and determined the level of IL-6 and the PMN% by ELISA, and the differences between the two groups were compared. The diagnostic efficacy of joint fluid IL-6 combined with PMN% in chronic PJI was analyzed using a receiver operating characteristic curve (ROC curve). RESULTS: The diagnosis of PJI using joint fluid IL-6 combined with PMN% presented an area under the curve of 0.983, which was more accurate than the areas under the curve for diagnosis using IL-6 and PMN% individually (0.901 and 0.914, respectively). The optimal threshold values for IL-6 and PMN% were 662.50 pg/ml and 51.09%, respectively. Their sensitivity and specificity were 96.67% and 93.33%, respectively. The accuracy of the diagnosis of PJI was 95.00%. CONCLUSIONS: Joint fluid IL-6 combined with PMN% can be used as an auxiliary method to detect chronic infection around the prosthesis after hip/knee arthroplasty. LEVEL OF EVIDENCE: Patients who underwent hip/knee revision at the First Hospital of Chongqing Medical University for periprosthetic infection or aseptic failure of the prosthesis after hip/knee arthroplasty from January 2018 to January 2020 were included. Trial registration This study was approved by the ethics committee of the First Hospital of Chongqing Medical University on September 26, 2018 (local ethics committee number: 20187101) and registered with the China Clinical Trials Registry (registration number: ChiCTR1800020440) with an approval date of December 29, 2018.

Detection of inguinal lymph nodes is promising for the diagnosis of periprosthetic joint infection.

Background: Localized inguinal lymphadenopathy often represents lower extremity pathogen infection, while normalized lymphadenopathy is associated with infection regression. We hypothesized that inguinal lymph nodes (LNs) were enlarged in Periprosthetic Joint Infection (PJI) patients and that normalized inguinal LNs would be a promising way to determine the timing of reimplantation. Methods: We prospectively enrolled 176 patients undergoing primary and revision hip or knee arthroplasty. All patients underwent ultrasound examination of inguinal LNs preoperatively. The diagnostic value of inguinal LNs in PJI was evaluated by the receiver operating characteristic (ROC) curve. Results: The median level of inguinal LNs was 26mm in the revision for PJI group compared with 12 mm in the aseptic revision group (p< 0.0001). The size of the inguinal LNs well distinguishes PJI from aseptic failure (AUC= 0.978) compare with ESR (AUC= 0.707) and CRP (AUC= 0.760). A size of 19mm was determined as the optimal threshold value of the inguinal LNs for the diagnosis of PJI, with a sensitivity of 92% and specificity of 96%. Conclusion: Ultrasonic analysis of inguinal LNs is a valuable piece of evidence for the diagnosis of PJI and evaluation of persistent infection.

Cerebral collateral circulation as an independent predictor for in-stent restenosis after carotid artery stenting.

Background: In-stent restenosis is a crucial problem after carotid artery stenting, but the exact predictors of in-stent restenosis remain unclear. We aimed to evaluate the effect of cerebral collateral circulation on in-stent restenosis after carotid artery stenting and to establish a clinical prediction model for in-stent restenosis. Methods: This retrospective case-control study enrolled 296 patients with severe carotid artery stenosis of C1 segment (≥70%) who underwent stent therapy from June 2015 to December 2018. Based on follow-up data, the patients were divided into the in-stent restenosis and no in-stent restenosis groups. The collateral circulation of the brain was graded according to the criteria of the American Society for Interventional and Therapy Neuroradiology/Society for Interventional Radiology (ASITN/SIR). Clinical data were collected, such as age, sex, traditional vascular risk factors, blood cell count, high-sensitivity C-reactive protein, uric acid, stenosis degree before stenting and residual stenosis rate, and medication after stenting. Binary logistic regression analysis was performed to identify potential predictors of in-stent restenosis, and a clinical prediction model for in-stent restenosis after carotid artery stenting was established. Results: Binary logistic regression analysis showed that poor collateral circulation was an independent predictor of in-stent restenosis (P=0.003). We also found that a 1% increase in residual stenosis rate was associated with a 9% increase in the risk of in-stent restenosis (P=0.02). Ischemic stroke history (P=0.03), family history of ischemic stroke (P<0.001), in-stent restenosis history (P<0.001), and nonstandard medication after stenting (P=0.04) were predictors of in-stent restenosis. The risk of in-stent restenosis was lowest when the residual stenosis rate was 12.5% after carotid artery stenting. Furthermore, we used some significant parameters to construct a binary logistic regression prediction model for in-stent restenosis after carotid artery stenting in the form of a nomogram. Conclusions: Collateral circulation is an independent predictor of in-stent restenosis after successful carotid artery stenting, and the residual stenosis rate tends to be below 12.5% to reduce restenosis risk. The standard medication should be strictly carried out for patients after stenting to prevent in-stent restenosis.

Preparation and Characterization of Biomimetic Functional Scaffold with Gradient Structure for Osteochondral Defect Repair.

Osteochondral (OC) defects cannot adequately repair themselves due to their sophisticated layered structure and lack of blood supply in cartilage. Although therapeutic interventions are reaching an advanced stage, current clinical therapies to repair defects are in their infancy. Among the possible therapies, OC tissue engineering has shown considerable promise, and multiple approaches utilizing scaffolds, cells, and bioactive factors have been pursued. The most recent trend in OC tissue engineering has been to design gradient scaffolds using different materials and construction strategies (such as bi-layered, multi-layered, and continuous gradient structures) to mimic the physiological and mechanical properties of OC tissues while further enabling OC repair. This review focuses specifically on design and construction strategies for gradient scaffolds and their role in the successful engineering of OC tissues. The current dilemmas in the field of OC defect repair and the efforts of tissue engineering to address these challenges were reviewed. In addition, the advantages and limitations of the typical fabrication techniques for gradient scaffolds were discussed, with examples of recent studies summarizing the future prospects for integrated gradient scaffold construction. This updated and enlightening review could provide insights into our current understanding of gradient scaffolds in OC tissue engineering.

Dietary Effects on Chronic Venous Disease.

BACKGROUND: Diet is fundamental to maintaining and improving human health. There is ample evidence identifying the beneficial and/or harmful effects of diet on noncommunicable diseases such as obesity, diabetes mellitus, and cardiovascular disease. However, the associations of the diet to chronic venous disease has not been fully described. METHODS: Data were collected through a cross-sectional survey conducted on 1,571 community-dwelling adults in 2018. Diet intake frequency was assessed using valid food group consumption frequency questionnaires. Multivariable logistic regression models were used to evaluate the association of diet with chronic venous disease. RESULTS: In total, 857 participants were diagnosed with chronic venous disease. Those who ate soybean products daily and 4-6 days/week had a 51-31% lower risk of chronic venous disease compared with those who only occasionally consumed soybean food, respectively. Participants who consumed eggs and egg products 1-3 days/week versus those who only occasionally ate eggs showed a lower risk of chronic venous disease [odds ratio (OR) 0.542, 95% confidence interval (CI) 0.375-0.782]. Eating fried food 4-6 days each week was associated with an increased risk of chronic venous disease (OR 3.872, 95% CI 1.263-11.599) compared with those who only occasionally ate fried foods. There is a decreasing tendency of the adjusted OR for eating soybean products daily with the severity of disease [chronic venous disease (C0-C2): OR 0.575, 95% CI 0.408-0.812; chronic venous insufficiency (C3-C6): OR 0.222, 95% CI 0.114-0.435]. CONCLUSIONS: A higher frequency in the consumption of soybean products and eggs were associated with a lower risk of chronic venous disease. High level of fried food consumption was positively associated with risk of chronic venous disease. There are certain specific trends in relation to dietary consumption and severity of disease, although these trends were less strong. These associations are largely independent of other dietary and nondietary factors.

Hypoxia-mimicking scaffolds with controlled release of DMOG and PTHrP to promote cartilage regeneration via the HIF-1α/YAP signaling pathway.

Efficiently driving chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) while avoiding undesired hypertrophy remains a challenge in the field of cartilage tissue engineering. Here, we report the sequential combined application of dimethyloxalylglycine (DMOG) and parathyroid hormone-related protein (PTHrP) to facilitate chondrogenesis and prevent hypertrophy. To support their delivery, poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated using a double emulsion method. Subsequently, these microspheres were incorporated onto a poly(l-lactic acid) (PLLA) scaffold with a highly porous structure, high interconnectivity and collagen-like nanofiber architecture to construct a microsphere-based scaffold delivery system. These functional constructs demonstrated that the spatiotemporally controlled release of DMOG and PTHrP effectively mimicked the hypoxic microenvironment to promote chondrogenic differentiation with phenotypic stability in a 3D culture system, which had a certain correlation with the interaction between hypoxia-inducible Factor 1 alpha (HIF-1α) and yes-associated protein (YAP). Subcutaneous implantation in nude mice revealed that the constructs were able to maintain cartilage formation in vivo at 4 and 8 weeks. Overall, this study indicated that DMOG and PTHrP controlled-release PLGA microspheres incorporated with PLLA nanofibrous scaffolds provided an advantageous 3D hypoxic microenvironment for efficacious and clinically relevant cartilage regeneration and is a promising treatment for cartilage injury.

The Ratio of IL-6 to IL-4 in Synovial Fluid of Knee or Hip Performances a Noteworthy Diagnostic Value in Prosthetic Joint Infection.

The diagnosis of prosthetic joint infection (PJI) is still a challenge, the ratio of interleukin-6 (IL-6) to IL-4 in the joint fluid of knee or hip was used to analyze whether the diagnostic accuracy of PJI can be improved. Between January 2017 and May 2022, 180 patients who developed pain after revision total hip or knee arthroplasty were enrolled retrospectively. 92 patients of PJI and 88 of aseptic failure were included. PJI was as defined by the Musculoskeletal Infection Society (MSIS). The content of IL-6 and IL-4 in synovial fluid of knee or hip were measured, and the areas under the receiver operating characteristic curve (ROC) and IL-6/IL-4 curve were analyzed to obtain a better diagnostic effect. The area under the curve of IL-6/IL-4 in synovial fluid of knee or hip was 0.9623, which was more accurate than ESR 0.5994 and C-reactive protein 0.6720. The optimal threshold of IL-6/IL-4 ratio was 382.10. Its sensitivity and specificity were 81.32% and 98.86%, respectively. The positive predictive value for the diagnosis of PJI was 98.91%. This study showed that the level of IL-6/IL-4 in synovial fluid of knee or hip could further improve the diagnostic accuracy for PJI.

Application of transcranial doppler in patients after stent-assisted coil embolization.

BACKGROUND AND PURPOSE: Patients with intracranial aneurysms treated with stent-assisted coil embolization (SACE) require radiological and clinical follow-up in view of in-stent stenosis (ISS). The aim of the study was to evaluate transcranial Doppler (TCD) as an alternative to more invasive digital subtraction angiography (DSA) in monitoring patients with SACE. METHODS: Over the course of 72 months, from January 2016 to December 2021, we analyzed 49 patients treated with SACE because of internal carotid artery (ICA) aneurysms (C6 ophthalmic segment or C7 communicating segment). DSA was performed in all patients at 24-months and TCD was examined preoperatively and at 3, 6, 12, and 24-months postoperatively. The degree of stenosis found on TCD was compared with the results of DSA. Preoperative and postoperative blood flow velocities, including peak systolic blood flow velocity (Vs), end diastolic velocity (Vd), and mean velocity (Vm), were compared and the optimal cutoff velocities for detecting stenosis were calculated. RESULTS: Pre-embolization middle cerebral artery (MCA) and intracranial terminal internal cerebral arteries (TICA) velocities and pulsatility index (PI) did not significantly differ between the ipsilateral and contralateral sides. The blood flow velocities, Vs, Vd, and Vm, on the operation side significantly increased after SACE (P < 0.05). Over the 24-month study period, 7 of the 49 patients (14.3%) exhibited angiographic ISS. ISS of TCD and DSA results at 24-months were compared and found to correlate well; the Cohen's κ coefficient was 0.851 (95% CI 0.651-1.051). The optimal cutoff velocity for detecting ISS was MCA Vs = 173.5 cm/s. CONCLUSIONS: TCD is a potentially useful adjunct for evaluating ISS after SACE.

Effect of intracranial venous collaterals on neurological outcomes in cerebral venous thrombosis.

This study identifies predictors of favourable intracranial venous collaterals and the effect of intracranial venous collaterals on outcomes and recanalization in patients with cerebral venous thrombosis (CVT). Data of 61 patients with CVT were retrospectively reviewed. Venous collateralization was defined as expanded cortical vein formation through different drainage pathways. Recanalization grades were classified into complete or partial recanalization based on images obtained during hospitalisation and follow-up. Independent predictors of collateral formation and poor prognosis were investigated via univariate and binary logistic regression analyses. The effects of different intracranial venous collaterals on recanalization in patients with CVT were assessed. A risk prediction nomogram for prognosis was constructed. Age ≤ 35 years (odds ratio (OR) = 7.067; 95% confidence interval (CI) = 1.776-28.277; P = 0.006) and male sex (OR = 5.490; 95% CI = 1.205-25.004; P = 0.028) were independent predictors of favourable venous collaterals. Venous collaterals were associated with early recanalization (P = 0.017) and not with long-term recanalization (P = 0.252). Male sex (OR = 0.047; 95% CI = 0.003-0.651; P = 0.023), subacute onset (OR = 0.026; 95% CI = 0.002-0.367; P = 0.007), and good collateral grade (OR = 0.168; 95% CI = 0.029-0.985; P = 0.048) were independent factors of favourable neurological outcomes at discharge. Haemorrhage on computed tomography at admission (OR = 10.868; 95% CI = 2.082-56.733; P = 0.005) was inversely correlated with prognosis. These findings suggested that male patients under 35 years of age are more likely to have favourable venous collaterals and good outcomes. Venous collaterals are significantly associated with early recanalization. These findings highlight the importance of venous collateral evaluation in patients with CVT.

Synovial Fluid Interleukin Levels Cannot Distinguish between Prosthetic Joint Infection and Active Rheumatoid Arthritis after Hip or Knee Arthroplasty.

Inflammatory arthritis affects the level of synovial inflammatory factors, which makes it more difficult to diagnose prosthetic joint infection (PJI) patients with inflammatory arthritis. The aim of this study was to analyze synovial interleukin levels to distinguish between PJI and active rheumatoid arthritis (RA) after a hip or knee arthroplasty. From September 2019 to September 2021, we prospectively enrolled patients with joint pain after arthroplasty due to aseptic prosthesis loosening (n = 39), acute RA (n = 26), and PJI (n = 37). Synovial fluid from the affected joint is obtained and tested with a standard enzyme-linked immunosorbent assay. Receiver operating characteristic curve (ROC) was analyzed for each biomarker. Interleukin (IL)-1ß, IL-6, and IL-8 showed promising value in differentiating of aseptic loosening from PJI, with areas under the curves (AUCs) of 0.9590, 0.9506, and 0.9616, respectively. Synovial IL-1ß, IL-6, and IL-8 showed limited value in distinguishing between PJI and acute episodes of RA after arthroplasty, with AUCs of 0.7507, 0.7069, and 0.7034, respectively. Interleukins showed satisfactory efficacy in differentiating aseptic loosening from PJI. However, when pain after arthroplasty results from an acute episode of RA, current synovial interleukin levels do not accurately rule out the presence of PJI.

Improved HbA1c and reduced glycaemic variability after 1-year intermittent use of flash glucose monitoring.

Flash glucose monitoring (FGM) was introduced in China in 2016, and it might improve HbA1c measurements and reduce glycaemic variability during T1DM therapy. A total of 146 patients were recruited from October 2018 to September 2019 in Liaocheng. The patients were randomly divided into the FGM group or self-monitoring blood glucose (SMBG) group. Both groups wore the FGM device for multiple 2-week periods, beginning with the 1st, 24th, and 48th weeks for gathering data, while blood samples were also collected for HbA1c measurement. Dietary guidance and insulin dose adjustments were provided to the FGM group patients according to their Ambulatory Glucose Profile (AGP) and to the SMBG group patients according to their SMBG measurements taken 3-4 times daily. All of the participants underwent SMBG measurements on the days when not wearing the FGM device. At the final visit, HbA1c, time in range (TIR), duration of hypoglycaemia and the number of diabetic ketoacidosis (DKA) events were taken as the main endpoints. There were no significant difference in the baseline characteristics of the two groups. At 24 weeks, the HbA1c level of the FGM group was 8.16 ± 1.03%, which was much lower than that of the SMBG group (8.68 ± 1.01%) (p = 0.003). The interquartile range (IQR), mean blood glucose (MBG), and the duration of hypoglycaemia in the FGM group also showed significant declines, compared with the SMBG group (p < 0.05), while the TIR increased in the FGM group [(49.39 ± 17.54)% vs (42.44 ± 15.49)%] (p = 0.012). At 48 weeks, the differences were more pronounced (p < 0.01). There were no observed changes in the number of episodes of DKA by the end of the study [(0.25 ± 0.50) vs (0.28 ± 0.51), p = 0.75]. Intermittent use of FGM by T1DM patients can improve their HbA1c and glycaemic control without increasing the hypoglycaemic exposure in insulin-treated individuals with type 1 diabetes in an developing country.

Clinical outcomes of venous self-expanding stent placement for iliofemoral venous outflow obstruction.

OBJECTIVE: In the present study, we evaluated the feasibility of a self-expanding venous stent for treating iliofemoral venous obstruction. METHODS: The present retrospective study reviewed the data from 49 patients who had undergone Zilver Vena (Cook Medical, Bloomington, Ind) stent placement for treatment of iliofemoral venous obstruction from September 2017 to March 2019. All patients had undergone received follow-up duplex ultrasound examinations to assess for stent patency. The Villalta scores and Venous Clinical Severity Scores (VCSSs) were also calculated to stratify the postoperative improvement in disease. RESULTS: Of the 49 patients, 19 had had acute deep vein thrombosis, 7, nonthrombotic iliac venous lesions, and 23, post-thrombotic syndrome. At 1 year after Zilver Vena stent placement, the primary, assisted primary, and secondary patency rates were 93.8%, 95.9%, and 97.9%, respectively. The baseline median Villalta score before treatment for those with post-thrombotic syndrome was 19 (range, 11-30), and the median VCSS for the patients with post-thrombotic syndrome and nonthrombotic iliac venous lesions was 11 (range, 6-25). At 1 year after stent placement, the median Villalta score for the post-thrombotic syndrome patients was 4.0 (range, 2-18), and the median VCSS for the post-thrombotic syndrome and nonthrombotic iliac venous lesions patients was 3.0 (range, 2-12). CONCLUSIONS: Venous placement of self-expanding stents offers excellent 1-year patency rates and improved the outcomes of patients with iliofemoral venous obstruction caused by acute deep vein thrombosis, nonthrombotic iliac venous lesions, and post-thrombotic syndrome.

Association of High Serum Homocysteine Levels and Severe Chronic Venous Disease.

BACKGROUND: Homocysteine (Hcy) is considered as a modifiable risk factor for vascular disease. This study was aimed to explore the association between serum concentration and the severity of primary chronic venous disease (CVD). METHODS: Clinical data of 582 patients diagnosed with primary CVD were collected and analyzed retrospectively. The Clinical Etiology Anatomy Pathophysiology classification system was used to grade the severity of chronic venous disease. Patients were divided into 2 groups (group A: C1-C3; group B: C4-C6). The association between serum homocysteine levels and the severity of primary chronic venous disease was investigated using rank sum test and logistic regression. RESULTS: The difference between the level of homocysteine in each grade has statistical significance. Group A has higher median Hcy concentrations than Group B (15.40 µmol/L vs. 14.05 µmol/L, P< 0.01). Further binary logistic regression showed no statistical significance among the level of Hcy (11.00-14.75 µmol/L [OR 0.66, 95% CI 0.40-1.11, P= 0.12], 14.75-20.38µmol/L [OR 0.97, 95% CI 0.59-1.69, P = 0.89], ≥20.38 µmol/L [OR 0.67, 95% CI 0.41-1.10, P = 0.11]), but age (OR 1.03, 95% CI 1.01-1.04, P< 0.01) and female (OR 0.41, 95% CI 0.28-0.59, P< 0.01) are associated with more severe stages of CVD. CONCLUSIONS: Higher level of Hcy is associated with more severe stages of CVD, but it not an independent risk factor. However, Advanced age and female are risk factors for CVD development based on logistic regression analysis.

Predictive Model for Pulmonary Embolism in Patients with Deep Vein Thrombosis.

BACKGROUND: To develop and verify a risk predictive model/scoring system for pulmonary embolism (PE) among hospitalized patients with deep venous thrombosis of the lower extremities (LDVT). METHODS: 776 patients with LDVT were enrolled in a case-control study between January 2016 and June 2017 from the Vascular Surgery Department of Shanxi Dayi Hospital, China. They were randomly divided into development (543 patients, 70%) and validation (233 patients, 30%) databases. Based on the results of pulmonary computed tomography arteriography, patients were divided into 2 categories; those with PE were designated as the case group, whereas those without comprised the controls. A logistic regression model and scoring system for PE in patients with LDVT was established in the development database and verified in the validation database. Scoring system (Shanxi Dayi Hospital score [SDH score]) was tabulated as follows: right lower extremity or bilateral lower extremities, 1; surgery or immobilization, 1; malignant tumor, 1; history of venous thromboembolism (VTE), 2; D-dimer >1,000 ng/mL, 2; and unprovoked, 2. Calibration and discrimination of the model were assessed by the Hosmer-Lemeshow goodness of fit test and the area under the receiver operating characteristic curve (AUC). Wells score, the Revised Geneva score, and the SDH score for predictive value of PE by AUC in the validation database were compared. RESULTS: 776 patients with LDVT were divided into 2 risk categories based on the scores from the risk model as follows: PE unlikely (score <3) and PE likely (score ≥3). Sensitivity, specificity, and crude agreement of the SDH score in the development database were 76.39%, 55.89%, and 61.33%, respectively. In the validation database, the logistic regression model showed good calibration and discriminative power. The Hosmer-Lemeshow goodness of fit test P value was >0.05, and the AUC was 0.705 (95% CI: 0.634-0.776, P < 0.001). The SDH score also showed good discriminative power, and the AUC was 0.702 (95% CI: 0.631-0.774, P < 0.001). Sensitivity, specificity, and crude agreement of the SDH score in the validation database were 67.61%, 61.73%, and 63.52%, respectively. AUC for the Wells score and the Revised Geneva score was 0.611 (95% CI: 0.533-0.688, P = 0.007) and 0.585 (95% CI: 0.503-0.666, P = 0.040), respectively. Difference of the AUC was not statistically significant between the Wells score and the SDH score (0.611 vs. 0.702, P = 0.059) but was so between the Revised Geneva score and the SDH score (0.585 vs. 0.702, P = 0.016). Sensitivity of the Wells score, Revised Geneva score, and the SDH score (64.79%, 67.61% vs. 67.61%) was not statistically significant. However, the specificity of the Wells score and Revised Geneva score was significantly lower than that of the SDH score (48.77%, 39.51% vs. 61.73%). CONCLUSIONS: Our logistic regression model and the SDH score based on 7 risk factors as right lower extremity, bilateral lower extremities, unprovoked, surgery or immobilization, malignant tumor, history of VTE, and D-dimer>1,000 ng/mL showed good calibration and discriminative power for the assessment of PE risk in patients with LDVT. The SDH score is more specific for PE prediction in the Chinese population, compared with the Wells score and the Revised Geneva score.

Naringenin improves insulin sensitivity in gestational diabetes mellitus mice through AMPK.

BACKGROUND: Gestational diabetes mellitus (GDM) is a temporary form of diabetes during pregnancy, which influences the health of maternal-child in clinical practice. It is still urgent to develop new effective treatment for GDM. Naringenin is a bioactive ingredient with multiple activities including anti-diabetic. In current study, the effects of naringenin on GDM symptoms, insulin tolerance, inflammation, and productive outcomes were evaluated and the underlying mechanisms were explored. METHODS: We administrated naringenin to GDM mice and monitored the GDM symptoms, glucose and insulin tolerance, inflammation and productive outcomes. We established tumor necrosis factor alpha (TNF-α)-induced insulin resistance skeletal muscle cell model and evaluated the effects of naringenin on reactive oxygen species (ROS) production, glucose uptake and glucose transporter type 4 (GLUT4) membrane translocation. RESULTS: We found that naringenin ameliorated GDM symptoms, improved glucose and insulin tolerance, inhibited inflammation, and improved productive outcomes. It was further found that naringenin inhibited TNF-α-induced ROS production, enhanced GLUT4 membrane translocation, and glucose uptake, which were abolished by inhibition of AMP-activated protein kinase (AMPK). CONCLUSION: Naringenin improves insulin sensitivity in gestational diabetes mellitus mice in an AMPK-dependent manner.

Characterization of internalin genes in Listeria monocytogenes from food and humans, and their association with the invasion of Caco-2 cells.

BACKGROUND: Internalins are surface proteins that are utilized by Listeria monocytogenes to facilitate its invasion into human intestinal epithelial cells. The expression of a full-length InlA is one of essential virulence factors for L. monocytogenes to cross the intestinal barrier in order to invade epithelial cells. RESULTS: In this study, the gene sequences of inlA in 120 L. monocytogenes isolates from food (n = 107) and humans (n = 13) were analyzed. Premature stop codon (PMSC) mutations in inlA were identified in 51 isolates (50 from food and 1 from human). Six mutation types of PMSCs were identified. Among the 51 isolates with PMSCs in inlA, there were 44 serogroup 1/2c, 3c isolates from food, of which seven belonged to serogroups 1/2a, 3a. A total of 153,382 SNPs in 2247 core genes from 42 genomes were identified and used to construct a phylogenetic tree. Serotype 1/2c isolates with inlA PMSC mutations were grouped together. Cell culture studies on 21 isolates showed that the invasion to Caco-2 cells was significantly reduced among isolates with inlA PMSC mutations compared to those without PMSC mutations (P < 0.01). The PMSC mutations in inlA correlated with the inability of the L. monocytogenes isolates to invade Caco-2 cells (Pearson's coefficient 0.927, P < 0.01). CONCLUSION: Overall, the study has revealed the reduced ability of L. monocytogenes to invade human intestinal epithelial cells in vitro was linked to the presence of PMSC mutations in inlA. Isolates with PMSC mutations shared the same genomic characteristics indicating the genetic basis on the potential virulence of L. monocytogenes invasion.

Increase in Ceftriaxone Resistance and Widespread Extended-Spectrum ß-Lactamases Genes Among Salmonella enterica from Human and Nonhuman Sources.

Salmonella producing ß-lactamases has spread rapidly worldwide and poses a serious threat to human and animal health. In this study, we characterized 220 ceftriaxone (CRO)-resistant isolates identified among 3153 Salmonella from humans, animals, food, and water collected in Shanghai, China. They were assessed for antimicrobial susceptibility, phenotypic identification of extended-spectrum ß-lactamases (ESBLs), and ß-lactamase genes and integrons. CRO resistance in Salmonella increased from 5.0% in 2011 to 8.4% in 2013. Salmonella Enteritidis (45.5%), Salmonella Typhimurium (20.9%) from humans, and Salmonella Indiana (14.5%) from poultry represented the majority of the CRO-resistant isolates. Many isolates were also resistant to other antimicrobials, including nalidixic acid (84.5%), sulfisoxazole (70.5%), and tetracycline (61.8%). Resistance to ciprofloxacin was also found in 33.6% of the isolates. Most isolates (98.2%) were confirmed as ESBL producers. Resistance genes such as blaCTX-M, blaTEM, and blaOXA were detected in 207 (94.1%), 99 (45%), and 53 (24.1%) isolates, respectively. Three types of integron I and one type of integron II were identified in 13 (5.9%) and 2 (0.9%) isolates, respectively. The integrons encompassed 10 different genes: dfrA1/12/17/25, aadA1/2/5, sat2, orfF, and ybeA. Our study underscores concern for increasing CRO resistance, and highlights the widespread ESBL genes in Salmonella enterica.