Laboratory features of effects of peloidotherapy and aromatherapy in patients with rheumatoid arthritis.

Peloidotherapy and aromatherapy have been used for years in the treatment of numerous inflammatory conditions, including rheumatoid arthritis (RA). The exact mechanism of their action in RA is unclear. The goal of our research is to determine the effect of peloidotherapy and aromatherapy on inflammation parameters in RA patients. Our study included 20 patients of both sexes, with confirmed diagnosis of RA, older than 18 years. Patients were treated during 28 days with combination of peloidotherapy and aromatherapy. Serum samples for detection of levels of inflammation parameters were taken at two intervals: before the start of therapy and at the end of treatment. The results of our study show that there were no significant changes in the parameters of the complete blood count. Nevertheless, a statistically significant decrease in the serum concentration of two markers of inflammation-interleukin-6 (IL-6) and nitrogen-oxide (NO)-was detected. Correlation analyses results say that there is a synchronized drop in the serum concentrations of CRP and the sedimentation rate, and the serum concentrations of fibrinogen and IL-6 are in the same relationship as well as serum levels of IL-6 and NO. Bearing in mind the importance of IL-6 and NO in the pathogenesis of inflammation in RA, we conclude that the application of our therapeutic protocol can be a significant add-on treatment to classic immunomodulators. Due to the small number of study participants, the lack of a control group, and the short follow-up time of patients, additional research is needed.

The role of solar and geomagnetic activity in endothelial activation and inflammation in the NAS cohort.

This study investigated the associations between solar and geomagnetic activity and circulating biomarkers of systemic inflammation and endothelial activation in the Normative Aging Study (NAS) cohort. Mixed effects models with moving day averages from day 0 to day 28 were used to study the associations between solar activity (sunspot number (SSN), interplanetary magnetic field (IMF)), geomagnetic activity (planetary K index (Kp index), and various inflammatory and endothelial markers. Biomarkers included intracellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), C-reactive protein (CRP), and fibrinogen. After adjusting for demographic and meteorological variables, we observed significant positive associations between sICAM-1 and sVCAM-1 concentrations and solar and geomagnetic activity parameters: IMF, SSN, and Kp. Additionally, a negative association was observed between fibrinogen and Kp index and a positive association was observed for CRP and SSN. These results demonstrate that solar and geomagnetic activity might be upregulating endothelial activation and inflammation.

Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study).

BACKGROUND: Vitamin D has an immunomodulatory role but the effect of therapeutic vitamin D supplementation in SARS-CoV-2 infection is not known. AIM: Effect of high dose, oral cholecalciferol supplementation on SARS-CoV-2 viral clearance. DESIGN: Randomised, placebo-controlled. PARTICIPANTS: Asymptomatic or mildly symptomatic SARS-CoV-2 RNA positive vitamin D deficient (25(OH)D<20 ng/ml) individuals. INTERVENTION: Participants were randomised to receive daily 60 000 IU of cholecalciferol (oral nano-liquid droplets) for 7 days with therapeutic target 25(OH)D>50 ng/ml (intervention group) or placebo (control group). Patients requiring invasive ventilation or with significant comorbidities were excluded. 25(OH)D levels were assessed at day 7, and cholecalciferol supplementation was continued for those with 25(OH)D <50 ng/ml in the intervention arm. SARS-CoV-2 RNA and inflammatory markers fibrinogen, D-dimer, procalcitonin and (CRP), ferritin were measured periodically. OUTCOME MEASURE: Proportion of patients with SARS-CoV-2 RNA negative before day-21 and change in inflammatory markers. RESULTS: Forty SARS-CoV-2 RNA positive individuals were randomised to intervention (n=16) or control (n=24) group. Baseline serum 25(OH)D was 8.6 (7.1 to 13.1) and 9.54 (8.1 to 12.5) ng/ml (p=0.730), in the intervention and control group, respectively. 10 out of 16 patients could achieve 25(OH)D>50 ng/ml by day-7 and another two by day-14 [day-14 25(OH)D levels 51.7 (48.9 to 59.5) ng/ml and 15.2 (12.7 to 19.5) ng/ml (p<0.001) in intervention and control group, respectively]. 10 (62.5%) participants in the intervention group and 5 (20.8%) participants in the control arm (p<0.018) became SARS-CoV-2 RNA negative. Fibrinogen levels significantly decreased with cholecalciferol supplementation (intergroup difference 0.70 ng/ml; P=0.007) unlike other inflammatory biomarkers. CONCLUSION: Greater proportion of vitamin D-deficient individuals with SARS-CoV-2 infection turned SARS-CoV-2 RNA negative with a significant decrease in fibrinogen on high-dose cholecalciferol supplementation. TRIAL REGISTER NUMBER: NCT04459247.

Evaluation of Hepatoprotective effects of different doses of Lyophilized Beetroot powder in albino rabbits.

Beta vulgaris L. is a vegetable most commonly consumed in salads and has been shown to possess multiple benefits. This research was carried out to observe the effects of Beta vulgaris powder at different doses orally in albino rabbits on liver biochemical parameters and coagulation. The study was carried out on albino rabbits which were divided into three groups designated as Group I (administered distilled water) Group II and III (administered beetroot powder at 500mg/kg and 1000mg/kg dose respectively) orally for 2 month duration. The sample was withdrawn at day 0, 30th and 60th day through cardiac puncture. The results showed that both doses of Beta vulgaris were considered safe for use as all the liver parameters were significantly decreased compared to control. Among both doses 500mg/kg dose was considered safer as it reduced the parameters significantly compared to 1000mg/kg dose. Blood coagulation factors at both the doses showed significant increase which was in reference range. Beta vulgaris is a highly beneficial dietary product with ample amount of flavonoids and anti-oxidant agents which might help in improving the liver function and also play a role in coagulation by increasing both fibrinogen levels and prothrombin time.

Therapeutic effects of different polar fractions of hawthorn extract on blood stasis model rats revealed by liquid chromatography-mass spectrometry metabolomics.

Hawthorn, a commonly used traditional Chinese medicine, has been suggested to have therapeutic effects on cardiovascular disease. However, effective fractions of hawthorn extract in the treatment of cardiovascular disease, together with possible therapeutic mechanisms, remain unclear. This study aimed to investigate the effects of four different polar fractions of hawthorn extract on blood stasis model rats, and explore the possible metabolic mechanisms by using a liquid chromatography-mass spectrometry metabolomics approach. Evaluation of hemorheology and fibrinogen showed that n-butanol and ethyl acetate fractions of hawthorn extract had significant therapeutic effects on blood stasis model rats. Furthermore, metabolomics analysis showed that n-butanol and ethyl acetate fractions of hawthorn extract could reverse imbalanced biomarkers in plasma and urine of blood stasis model rats. Additionally, metabolic pathway analysis revealed that plasma biomarkers were responsible for several important pathways, including d-glutamine and d-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, alanine, aspartate, and glutamate metabolism, sphingolipid metabolism, and arginine biosynthesis. Meanwhile, urine biomarkers were responsible for some important pathways, including phenylalanine metabolism, tyrosine metabolism, and lysine degradation. This study demonstrated that n-butanol and ethyl acetate fractions of hawthorn extract had significant therapeutic effects on blood stasis model rats, and the underlying mechanisms involved multiple metabolic pathways.

Pathogen reduction of whole blood: Supplementing fibrinogen partly corrects clot formation in a massive transfusion model.

BACKGROUND: The use of whole blood (WB) to treat trauma patients is becoming more common. Similar to the treatment of individual components, pathogen inactivation (PI) technologies are available to treat WB. The impact of PI on WB function is not well understood. This study investigated the impact of PI of WB with riboflavin/ultraviolet (UV) light on its hemostatic function by modeling transfusion scenarios for trauma patients and assessing transfusion efficacy by rotational thromboelastometry (ROTEM). As fibrinogen is affected by PI of WB, the effect of fibrinogen supplementation commonly used in trauma patients was also analyzed in this model. STUDY DESIGN AND METHODS: Trauma transfusion scenarios were simulated by mixing untreated WB or WB treated with the Mirasol PI technology (riboflavin/UV) in different ratios with hemodiluted blood, and the thromboelasticity was monitored by ROTEM. The impact of supplementation with the fibrinogen concentrate RiaSTAP was investigated in this model. RESULTS: Pathogen-inactivated WB (PI-WB) showed decreased activity in the hemostatic profile compared to the untreated control. Hemodiluted blood at a hematocrit (hct) of 20%, which was reconstituted with PI-WB or untreated WB, exhibited increased alpha values, maximum clot firmness, and clot formation time. Simulating transfusion scenarios by blood replacement with PI-WB resulted in a significant difference in ROTEM parameters between reconstituted PI-treated and -untreated WB (p ≥ .05). The effect of PI treatment waned when PI-WB was enriched with fibrinogen. CONCLUSION: ROTEM investigations suggest that PI treatment has a negative impact on WB clot formation unless fibrinogen supplementation is used.

Inverse association between bone mineral density and fibrinogen in menopausal women.

OBJECTIVE: Inflammatory diseases are risk factors for osteoporosis. We aimed to explore whether fibrinogen, which is linked to chronic inflammation, is associated with bone mineral density (BMD) in menopausal women. METHODS: In this cross-sectional study, we analyzed 339 menopausal women from Zhejiang Province between January 2016 and October 2019. Linear regression analysis was performed to assess the relationship between fibrinogen and BMD. RESULTS: Significant inverse association was observed between the serum fibrinogen level and BMD in menopausal women. The mean BMD in each quartile of fibrinogen level was 0.901, 0.897, 0.892, and 0.855 g/cm2, respectively (p = 0.027). After adjusting for age, body mass index, metabolic profiles, blood inflammatory factors, and serum levels of estradiol, calcium, phosphorus, and alkaline phosphatase, fibrinogen levels remained significantly associated with BMD (regression coefficients for quartiles 1-3 vs. quartile 4 were 0.046, 0.027, and 0.036, respectively; p for trend <0.05). CONCLUSIONS: Higher fibrinogen levels were associated with lower BMD in menopausal women, which was independent of age, body mass index, estradiol, and other factors. Therefore, serum fibrinogen can be used as a new predictor of reduced BMD in menopausal women.

Characterization of Fibrinogen as a Key Modulator in Patients with Wilson's Diseases with Functional Proteomic Tools.

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by defects in the ATPase gene (ATP7B). The various clinical features result from the massive accumulation of copper in the liver, cornea and basal ganglia. Although WD can be effectively treated with proper medicine, this disease is difficult to clearly diagnose due to its indefinite symptoms. In the current study, we achieved a positive correlation between clinical symptoms and the enzymatic activity of ceruloplasmin in WD patients. Furthermore, proteome profiles of plasma as well as network analysis demonstrated that fibrinogen is a critical indicator which is significantly unregulated in WD subjects in comparison to healthy donors and closely linked to pathogenesis of WD. Here, we applied 2DE-immunoblots and immunohistochemistry to verify the protein level and localization in situ. The enhanced expression of fibrinogen in the plasma of WD subjects with respect to that of healthy controls and patients with distinct disorders was also confirmed by utilizing clinical samples. As expected, application of high dose of copper induced expression of fibrinogen, while knockdown of ceruloplasmin also resulted in upregulation of fibrinogen as well as elimination of superoxide dismutase (SOD), leading to increased oxidative stress in cells. In summary, the liver injury or oxidative stress induced by the progression of WD may account for the obvious increase of fibrinogen, which in turn triggers inflammatory responses and interferes coagulation cascades; this finding sheds light on the early detection and diagnosis of WD.

The relationship of plasma fibrinogen with clinicopathological stages and tumor markers in patients with non-small cell lung cancer.

Numerous studies have shown that the blood of cancer patients are generally in hypercoagulable statement. The aim of the present research is to study the relationships of plasma fibrinogen (Fbg) levels with clinicopathological stages (CS) and tumor markers of non-small cell lung cancer (NSCLC).Baseline information, plasma Fbg levels, CS, and expression level of tumor markers were collected from medical records retrospectively. Unitary linear regression was used to analyze the relationships between continuous variables and Fbg, and multiple linear regression was used to analyze the relationships between categorical variables and Fbg. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (Version 4) for NSCLC were adopted to evaluate CS.A total of 652 NSCLC patients were included. Compared with the females, male patients had higher mean plasma Fbg levels (P < .001). The later the N stages (P = .002), M stages (P = .002), and CS (P = .001) were, the higher the average plasma Fbg levels were. The levels of squamous cell carcinoma antigen (P = .001), carbohydrate antigen 125 (P = .041), and neuron-specific enolase (P < .001) were positively correlated with plasma Fbg concentration. The plasma level of Fbg in lung adenocarcinoma patients (P < .001) was the lowest, while that of lung squamous cell carcinoma patients (P < .001) was the highest in NSCLC patients.The plasma Fbg concentration is related to gender, CS, and tumor markers in patients with NSCLC.

Development of an aerosolized Mannheimia haemolytica experimental pneumonia model in clean-catch colostrum-deprived calves.

Mannheimia haemolytica is an important cause of bovine respiratory disease (BRD). BRD is usually a multifactorial disease with host factors and viral infections influencing pathogenesis. Previous studies that have attempted to experimentally induce pneumonia using aerosolized M. haemolytica alone have produced inconsistent results, yet an aerosol model would be useful to study the details of early infection and to investigate the role of innate defences in pathogenesis. The objective of these studies was to develop and characterize an aerosolized M. haemolytica disease model. In an initial study, conventionally raised calves with higher levels of antibody against M. haemolytica leukotoxin developed acute respiratory distress and diffuse alveolar damage, but did not develop bronchopneumonia, following challenge with M. haemolytica serotype 1. Clean-catch colostrum-deprived calves challenged with 1 × 1010 colony forming units of M. haemolytica serotype 1 consistently developed bronchopneumonia, with elevations in rectal temperature, serum haptoglobin, plasma fibrinogen, and blood neutrophils. Mannheimia haemolytica serotype 1 was consistently isolated from the nasal cavities and lungs of challenged calves. Despite distribution of aerosol and isolation of M. haemolytica in all lung lobes, gross lesions were mainly observed in the cranioventral area of lung. Gross and histologic lesions included neutrophilic bronchopneumonia and fibrinous pleuritis, with oat cells (necrotic neutrophils with streaming nuclei), and areas of coagulative necrosis, which are similar to lesions in naturally occurring BRD. Thus, challenge with M. haemolytica serotype 1 and use of clean-catch colostrum-deprived calves with low or absent antibody titres allowed development of an effective aerosol challenge model that induced typical clinical disease and lesions.

Evaluation of global laboratory methods and establishing on-therapy ranges for monitoring apixaban and rivaroxaban: Experience at a single institution.

BACKGROUND: Apixaban and rivaroxaban are approved for the prevention and treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), and embolic stroke in atrial fibrillation (AF) patients. The aim of this study was to find appropriate methods of monitoring the anticoagulant effects of are direct oral anticoagulants (DOACs) and establish on-therapy ranges using conventional tests. METHODS: A total of 184 samples were collected from 91 patients receiving DOACs. Concentrations of apixaban and rivaroxaban in plasma were accessed by an anti-factor Xa chromogenic assay. PT, APTT, antithrombin, D-dimer, dRVVT screen/confirm, FDP, and fibrinogen levels were measured. On-therapy ranges were calculated by substituting previously reported trough plasma concentrations of DOACs. RESULTS: Anti-factor Xa chromogenic assay-based DOACs levels were 26.0-279.5 (115.9 ± 56.5) ng/mL for apixaban at 2.5 mg BID, 19.9-565.1 (205.3 ± 162.4) ng/mL for apixaban at 5 mg BID, 2.3-395.3 (205.3 ± 162.4) ng/mL for rivaroxaban at 15 mg OD, 3.6-494.8 (119.6 ± 95.1) ng/mL for rivaroxaban at 20 mg OD, and 9.6-431.4 (140.8 ± 113.6) ng/mL for rivaroxaban at 15 mg BID. PT (%), antithrombin, and dRVVT confirm tests showed good correlation with plasma apixaban levels. Plasma rivaroxaban concentrations were correlated well with PT (sec), PT (%),and dRVVT confirm results. On-therapy ranges established for dRVVT confirm test by linear regression were as follows: 1.32-1.52 for apixaban 2.5 mg BID, 1.12-1.75 for apixaban 5 mg BID, 1.11-1.78 for rivaroxaban 15 mg OD, 1.09-1.64 for rivaroxaban 20 mg OD, and 1.22-1.81 for rivaroxaban 20 mg BID. CONCLUSIONS: Apixaban concentrations were well correlated with PT (%), antithrombin, and dRVVT confirm test. Rivaroxaban concentrations showed good correlation with PT (sec), PT (%), and dRVVT confirm test.

Assessment of anti-coagulant activity of Nelumbo nucifera fruit.

The herbal agents rich in flavonoids are progressively becoming popular these days as they are considered to have anti-oxidant effects and also lack bothersome effects. That's why existing research was encircled around the anti-coagulant effect of Nelumbo nucifera fruit (NNF) as it is also a rich source of flavonoids and cultivated in abundance especially in tropical regions of Asia but its usefulness as anti-coagulant agent was never determined pharmacologically. Anticoagulant assessment was done in thirty five male Wister rats which were separated equally in 5 groups. Results of the current study revealed that NNF 200mg/kg significantly prolonged prothrombin time and thrombin time, whereas fibrinogen level was highly significantly reduced as compared to control. Fibrinogen level was also reduced highly significantly with NNF 100 mg/kg as compared to control without affecting other parameters of coagulation i.e. activated partial thromboplastin time, prothrombin time and thrombin time. NNF exhibited strong anti-coagulant activity which may be due to the inhibitory effects on platelet activation, adhesion and aggregation along with inhibitory effects on thromboxane A2 formation. Presence of alkaloid i.e. neferine and flavonoids in it may be a reason of its anti-coagulant activity but more pre-clinical and clinical evaluation needs to be conducted to establish these findings.

Hyperfibrinogenemia is a poor prognostic factor in diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas worldwide. Previous studies indicated that hyperfibrinogenemia was a poor predictor in various tumors. The purpose of our study was to evaluate the prognostic effect of hyperfibrinogenemia in DLBCL. Data of 228 patients, who were diagnosed with DLBCL in our hospital between May 2009 and February 2016, were analyzed retrospectively. The Kaplan-Meier method and Cox regression were performed to find prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curve and the areas under the curve were used to evaluate the predictive accuracy of predictors. Comparison of characters between groups indicated that patients with high National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score (4-8) and advanced stage (III-IV) were more likely to suffer from hyperfibrinogenemia. The Kaplan-Meier method revealed that patients with hyperfibrinogenemia showed inferior PFS (P < 0.001) and OS (P < 0.001) than those without hyperfibrinogenemia. Multivariate analysis showed that hyperfibrinogenemia was an independent prognostic factor associated with poor outcomes (HR = 1.90, 95% CI: 1.15-3.16 for PFS, P = 0.013; HR = 2.65, 95% CI: 1.46-4.79 for OS, P = 0.001). We combined hyperfibrinogenemia and NCCN-IPI to build a new prognostic index (NPI). The NPI was demonstrated to have a superior predictive effect on prognosis (P = 0.0194 for PFS, P = 0.0034 for OS). Hyperfibrinogenemia was demonstrated to be able to predict poor outcome in DLBCL, especially for patients with advanced stage and high NCCN-IPI score. Adding hyperfibrinogenemia to NCCN-IPI could significantly improve the predictive effect of NCCN-IPI.

Longitudinal associations of sauna bathing with inflammation and oxidative stress: the KIHD prospective cohort study.

PURPOSE: We sought to determine cross-sectional and longitudinal associations of frequency of sauna bathing with high sensitivity C-reactive protein (hsCRP), fibrinogen, leucocyte count and gamma-glutamyltransferase (GGT). DESIGN: Baseline sauna bathing habits were assessed in 2269 men aged 42-61 years. Concentrations of hsCRP, fibrinogen, leucocyte count, and GGT were determined at baseline and 11 years later. The associations of sauna bathing frequency with baseline and 11-year hsCRP, fibrinogen, leucocyte count, and GGT levels were examined using robust multivariate regression analyses. RESULTS: In baseline analysis, 4-7 sauna sessions/week (compared with 1 sauna session/week) was associated with -0.84 mg/l (95% CI, -1.55, -0.14; p = .019) lower hsCRP; -0.07 g/l (95% CI, -0.15, 0.02; p = .112) lower fibrinogen; and -0.28 × 109/l (95% CI, -0.51, -0.06; p = .015) lower leucocyte count, after multivariable adjustment. In longitudinal analysis, the corresponding estimates were -1.66 mg/l (95% CI, -3.13, -0.19; p = .027); -0.16 g/l (95% CI, -0.31, -0.02; p = .031); and -0.49 × 109/l (95% CI, -0.85, -0.14; p = .007) respectively. Sauna bathing frequency was not associated with GGT at baseline and 11 years. CONCLUSION: Observational evidence supports the hypothesis that reduction in inflammation may be one of the pathways linking frequent sauna bathing with decreased risk of acute and chronic disease conditions. KEY MESSAGES Cross-sectional evidence or short-term studies suggest Finnish sauna bathing may exert its beneficial health effects via reduction in inflammation and oxidative stress; however, the long-term effects of sauna bathing on these outcomes are uncertain. In this population-based prospective cohort study, frequent sauna sessions significantly decreased levels of inflammatory markers at baseline and 11-year follow-up; but had no effect on oxidative stress. The health benefits of sauna bathing may in part be mediated via reduced systemic inflammation.

Rapid weight reduction does not impair athletic performance of Taekwondo athletes - A pilot study.

In combat sports such as taekwondo (TKD), athletes rapidly reduce body weight to achieve a desired weight category. Competition takes place 16-24 h after weigh-in and thus, the recovery time is an important factor for competition performance. The purpose of this study was to investigate the impact of rapid weight reduction (RWR) on athletic performance and associated hemorheological properties considering relevant recovery time. Five male TKD athletes reduced body weight by 5% within 3½ days. A simulated competition day (SCD) was carried out after a 16 h recovery period. Parameters were measured before RWR, at weigh-in and before and after three TKD simulation matches (SMs) at SCD. Same set-up was conducted but without RWR as control. Basal blood parameters, red blood cells (RBC) deformability and aggregation, serum glucose and fibrinogen were determined. During SMs, heart rate (HRpeak, HRmean), oxygen uptake (VO2peak, VO2mean), peak lactate (Peak La-), difference of lactate (ΔLa) and energy systems (anaerobic-alactic, -lactic and aerobic) were analyzed. Basal blood parameters remained unaltered during the interventions. RBC deformability was reduced and aggregation was increased after RWR but values returned to baseline after recovery and were not affected by the SMs. Glucose level was not affected by the interventions. Kick frequency in SMs was higher after RWR which might be responsible for higher HRpeak, VO2peak, VO2mean, Peak La-, ΔLa- and aerobic demand. The 16 h recovery is sufficient to regenerate measured physiological and hemorheological parameters. TKD-specific performance was not negatively affected during SMs after RWR.

[Comparative study on promoting blood effects of Danshen-Honghua herb pair with different preparations based on chemometrics and multi-attribute comprehensive index methods].

To evaluate the promoting blood circulation and removing blood stasis effects of Danshen-Honghua(DH) herb pair with different preparations (alcohol, 50% alcohol and water) on blood rheology and coagulation functions in acute blood stasis rats, and optimize the best preparation method of DH based on principal component analysis(PCA), hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods. Ice water bath and subcutaneous injection of adrenaline were both used to establish the acute blood stasis rat model. Then the blood stasis rats were administrated intragastrically with DH (alcohol, 50% alcohol and water) extracts. The whole blood viscosity(WBV), plasma viscosity(PV), erythrocyte sedimentation rate(ESR) and haematocrit(HCT) were tested to observe the effects of DH herb pair with different preparations and doses on hemorheology of blood stasis rats; the activated partial thromboplastin time(APTT), thrombin time(TT), prothrombin time(PT), and plasma fibrinogen(FIB) were tested to observe the effects of DH herb pair with different preparations on blood coagulation function and platelet aggregation of blood stasis rats. Then PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods were all used to comprehensively evaluate the total promoting blood circulation and removing blood stasis effects of DH herb pair with different preparations. The hemorheological indexes and coagulation parameters of model group had significant differences with normal blank group. As compared with the model group, the DH herb pair with different preparations at low, middle and high doses could improve the blood hemorheology indexes and coagulation parameters in acute blood stasis rats with dose-effect relation. Based on the PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods, the high dose group of 50% alcohol extract had the best effect of promoting blood circulation and removing blood stasis. Under the same dose but different preparations, 50% alcohol DH could obviously improve the hemorheology and blood coagulation function in acute blood stasis rats. These results suggested that DH herb pair with different preparations could obviously ameliorate the abnormality of hemorheology and blood coagulation function in acute blood stasis rats, and the optimized preparation of DH herb pair on promoting blood effects was 50% alcohol extract, providing scientific basis for more effective application of the DH herb pair in modern clinic medicine.

Effects of a Single-Dose Interscalene Block on Pain and Stress Biomarkers in Patients Undergoing Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial.

PURPOSE: To compare the effects of a single-dose interscalene block and general anesthesia (SISB/GA) with the effects of GA only in the early postoperative period after arthroscopic rotator cuff repair by evaluating subjective pain visual analog scale scores and objective pain-related stress biomarkers. METHODS: Patients refractory to conservative treatment of the affected shoulder were enrolled in this prospective, randomized endpoint study. Patients diagnosed with a rotator cuff tear (1-4 cm) based on magnetic resonance imaging were included. Exclusion criteria were small (<1 cm) and massive (>4 cm) rotator cuff tears. Thirty-one patients each were randomized into the SISB/GA and GA treatment groups. Preoperative pain scores were measured at 6:00 AM on the day of surgery, measured again at 1 and 6 hours postoperatively, and then every 6 hours until 3 days postoperatively. Blood sampling was performed to evaluate the stress biomarkers insulin, dehydroepiandrosterone sulfate, and fibrinogen preoperatively at 6:00 AM on the day of surgery and postoperatively at 18, 42, and 66 hours (6:00 AM on postoperative days 1-3). RESULTS: Pain scores were significantly decreased in the SISB/GA group (2.50 ± 0.94) versus the GA group (3.82 ± 1.31) on the day of surgery (P < .001), and especially at 6 hours postoperatively (SISB/GA: 2.42 ± 1.43; GA: 4.23 ± 2.17; P < .001). Insulin was decreased significantly in the SISB/GA group (10.55 ± 7.92 µU/mL) versus the GA group (20.39 ± 25.60 µU/mL) at 42 hours postoperatively (P = .048). There was no significant change in dehydroepiandrosterone sulfate or fibrinogen over time (P > .05). CONCLUSIONS: After arthroscopic rotator cuff repair, an SISB effectively relieved pain on the day of surgery without any complications. In addition, insulin levels were significantly reduced at 42 hours postoperatively. LEVEL OF EVIDENCE: Level I, prospective randomized controlled trial.

LDL apheresis activates the complement system and the cytokine network, whereas PCSK9 inhibition with evolocumab induces no inflammatory response.

BACKGROUND: Low-density lipoprotein (LDL) apheresis is an extracorporeal treatment modality used in high-risk coronary patients. It may, however, induce complement activation and downstream inflammation due to bio-incompatibility. OBJECTIVE: We explored changes in soluble inflammatory markers when changing from LDL apheresis to the novel PCSK9 inhibitor evolocumab. METHODS: Three patients with familial hypercholesterolemia participated. Blood samples (EDTA plasma) for complement activation and markers of inflammation were obtained before (baseline) and after LDL apheresis week at 0 and before biweekly administration of evolocumab at weeks 1, 3, 5, and 7. Complement activation was measured by ELISA and cytokines by multiplex technology. RESULTS: Complement activation products C3a and Bb were both significantly higher after LDL apheresis compared to baseline (P = .01), returned to baseline levels before administration of evolocumab and remained low through week 7. C4d was unchanged during LDL apheresis, whereas TCC was slightly higher after apheresis compared to baseline and week 7 without statistical difference. MCP-1 was higher after LDL apheresis compared to baseline (P = .04), returned to baseline levels before administration of evolocumab and remained low through week 7. There were minor changes for other cytokines including TNF, IFN-γ, MIP-1α, MIP-1ß, with some higher and some lower after apheresis; however, none of these changes were statistically significant. Fibrinogen and CRP were lower after LDL apheresis and had returned to levels comparable to baseline at week 7, statistically significant however only for fibrinogen. CONCLUSIONS: LDL apheresis activated the alternative complement system significantly as reflected by an increase in C3a and Bb. PCSK9 inhibition did not affect complement or cytokines during 7 weeks follow-up.