Characterization and pharmacokinetics of cinnamon and star anise compound essential oil pellets prepared via centrifugal granulation technology.

Cinnamon and star anise essential oils are extracted from natural plants and provide a theoretical basis for the development and clinical application of compound essential oil pellets. However, cinnamon oil and star anise oil have the characteristics of a pungent taste, extreme volatility, poor palatability, and unstable physical and chemical properties, which limit their clinical use in veterinary medicine. In this study, the inhibitory effects of cinnamon oil and star anise oil on Escherichia coli and Salmonella were measured. Compound essential oil pellets were successfully prepared by centrifugal granulation technology. Subsequently, the in vitro dissolution of the pellets and their pharmacokinetics in pigs were investigated. The results showd that, cinnamon and star anise oils showed synergistic or additive inhibitiory effects on Escherichia coli and Salmonella. The oil pellets had enteric characteristics in vitro and high dissolution in vitro. The pharmacokinetic results showed that the pharmacokinetic parameters Cmax and AUC were directly correlated with the dosage and showed linear pharmacokinetic characteristics, which provided a theoretical basis for the development and clinical application of compound essential oil pellets.

Intranasal B5 promotes mucosal defence against Actinobacillus pleuropneumoniae via ameliorating early immunosuppression.

Actinobacillus pleuropneumoniae (APP) is an important pathogen of the porcine respiratory disease complex, which leads to huge economic losses worldwide. We previously demonstrated that Pichia pastoris-producing bovine neutrophil ß-defensin-5 (B5) could resist the infection by the bovine intracellular pathogen Mycobacterium bovis. In this study, the roles of synthetic B5 in regulating mucosal innate immune response and protecting against extracellular APP infection were further investigated using a mouse model. Results showed that B5 promoted the production of tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, and interferon (IFN)-ß in macrophages as well as dendritic cells (DC) and enhanced DC maturation in vitro. Importantly, intranasal B5 was safe and conferred effective protection against APP via reducing the bacterial load in lungs and alleviating pulmonary inflammatory damage. Furthermore, in the early stage of APP infection, we found that intranasal B5 up-regulated the secretion of TNF-α, IL-1ß, IL-17, and IL-22; enhanced the rapid recruitment of macrophages, neutrophils, and DC; and facilitated the generation of group 3 innate lymphoid cells in lungs. In addition, B5 activated signalling pathways associated with cellular response to IFN-ß and activation of innate immune response in APP-challenged lungs. Collectively, B5 via the intranasal route can effectively ameliorate the immune suppression caused by early APP infection and provide protection against APP. The immunization strategy may be applied to animals or human respiratory bacterial infectious diseases. Our findings highlight the potential importance of B5, enhancing mucosal defence against intracellular bacteria like APP which causes early-phase immune suppression.

A V-shaped association between high-density lipoprotein cholesterol levels and poor outcomes in patients after percutaneous coronary intervention.

BACKGROUND: High density lipoprotein cholesterol (HDL-C) is considered as "good cholesterol". Recent evidence suggests that a high HDL-C level may increase the risk of poor outcomes in some populations. PURPOSE: To investigate the association between HDL-C levels and poor outcomes in patients after percutaneous coronary intervention (PCI). METHODS: Patients undergoing PCI during January 2012 and December 2018 were consecutively recruited and divided into three groups with different HDL-C levels: HDL-C ≤ 25 mg/dL, 25 < HDL-C ≤ 60 mg/dL, HDL-C > 60 mg/dL by the restricted cubic spline (RCS) analysis and assessed for all-cause mortality (ACM). The association between HDL-C levels and poor outcomes was assessed by multivariable cox regression analysis. RESULTS: The patients were followed with a median duration of 4 years. Of the 7284 participants, 727 all-cause deaths and 334 cardiovascular deaths occurred. A V-shaped association of HDL-C with the prognosis was observed, patients with either excessively low or high HDL-C levels reporting a higher risk than those with midrange values. After adjustment for confounding factors, the former exhibited a higher cumulative rate of ACM and cardiovascular mortality (CM) than the latter [low HDL-C: for ACM, hazard ratio (HR), 1.96; 95%CI, 1.41, 2.73, P < 0.001; for CM, HR, 1.66; 95%CI, 1.03, 2.67; P = 0.037; high HDL-C: for ACM, HR, 1.73; 95%CI, 1.29, 2.32, P < 0.001; for CM, HR, 1.73; 95%CI, 1.16, 2.58; P = 0.007]. CONCLUSION: HDL-C levels display a V-shaped association with poor outcomes in patients after PCI, with excessively high or low HDL-C suggesting a higher mortality risk. An optimal HDL-C level may fall in the range of 25-60 mg/dL.

The predictive value of the neutrophil/platelet ratio on in-hospital adverse events and long-term prognosis in patients with coronary artery disease after percutaneous coronary intervention and its possible internal mechanism.

The neutrophil-to-platelet ratio (NPR) is considered to be an indicator of inflammatory status. The value of the NPR in predicting in-hospital adverse events (AEs) and long-term prognosis after percutaneous coronary intervention (PCI) in coronary artery disease (CAD) patients has not yet been reported. Meanwhile, the mechanisms behind its predictive value for long-term prognosis remain unreported as well. The study retrospectively enrolled 7284 consecutive patients with CAD undergoing PCI from January 2012 to December 2018. Multivariable logistic regression analysis, multivariable Cox regression analysis, Kaplan‒Meier (KM) curve analysis, restricted cubic spline (RCS) curve analysis, and sensitivity analysis were used in the study. All-cause death was the endpoint of the study. According to the median value of the NPR, the patients were divided into two groups: the high group (NPR ≥ 0.02, n = 3736) and the low group (NPR < 0.02, n = 3548). Multivariate logistic regression analysis demonstrated that a high NPR was a risk factor for in-hospital AEs [odds ratio (OR) = 1.602, 95% CI 1.347-1.909, p = 0.001]. During a mean follow-up period of 3.01 ± 1.49 years, the multivariate Cox regression analysis showed that a high NPR affected the long-term prognosis of patients (HR 1.22, 95% CI 1.03-1.45, p = 0.025) and cardiac death (HR 1.49, 95% CI 1.14-1.95, p = 0.003). The subgroup analysis showed that the NPR was affected by age and sex. The mediation analysis identified that the effect of the NPR on long-term outcomes is partially mediated by serum creatinine (Scr) and triglycerides. The NPR may be a convenient indicator of in-hospital AEs and poor long-term and cardiac outcomes in CAD patients. It might have impacted prognosis through effects on kidney function and lipid metabolism.

Prognostic value of triglyceride glucose index in population at high cardiovascular disease risk.

BACKGROUND: Early identification of populations at high cardiovascular disease (CVD) risk and improvement of risk factors can significantly decrease the probability of CVD development and improve outcomes. Insulin resistance (IR) is a CVD risk factor. The triglyceride glucose (TyG) index is a simple and reliable index for evaluating IR. However, no clinical studies on the prognostic value of the TyG index in a high risk CVD population have been conducted. This study evaluated the relationship between the TyG index and prognosis in a high risk CVD population. METHODS: This study enrolled 35,455 participants aged 35-75 years who were at high CVD risk and visited selected health centers and community service centers between 2017 and 2021. Their general clinical characteristics and baseline blood biochemical indicators were recorded. The TyG index was calculated as ln[fasting triglyceride (mg/dl)× fasting blood glucose (mg/dl)/2]. The endpoints were all-cause death and cardiovascular death during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the TyG index and endpoints. RESULTS: In the overall study population, the mean age of all participants was 57.9 ± 9.6 years, 40.7% were male, and the mean TyG index was 8.9 ± 0.6. All participants were divided into two groups based on the results of the RCS analysis, with a cut-off value of 9.83. There were 551 all-cause deaths and 180 cardiovascular deaths during a median follow-up time of 3.4 years. In the multivariate Cox proportional hazard model, participants with a TyG index ≥ 9.83 had a higher risk of all-cause death (Hazard ratio [HR] 1.86, 95% Confdence intervals [CI] 1.37-2.51, P<0.001) and cardiovascular death (HR 2.41, 95%CI 1.47-3.96, P = 0.001) than those with a TyG index < 9.83. Subgroup analysis revealed that there was no interaction between the TyG index and variables in all subgroup analyses. CONCLUSIONS: The high TyG index was associated with an increased risk of all-cause death and cardiovascular death in people at high risk of CVD. This finding demonstrates the value of the TyG index in the primary prevention of CVD. TRIAL REGISTRATION: retrospectively registered, the registration number is K2022-01-005 and the date is 2022.01.30.

Predictive Value of Systemic Inflammation Score for Contrast-Associated Acute Kidney Injury and Adverse Outcomes Among Patients Undergoing Elective Percutaneous Coronary Intervention.

Purpose: Prior research has demonstrated a key role of systemic inflammatory state in the pathogenesis and progression of contrast-associated acute kidney injury (CA-AKI). Recently, the systemic inflammation score (SIS) has been introduced to evaluate the inflammatory status, utilizing the lymphocyte-to-monocyte ratio (LMR) and albumin. The primary objective of this study was to determine whether the SIS can predict CA-AKI and long-term prognosis in patients undergoing elective percutaneous coronary intervention (PCI). Patients and Methods: A total of 5726 patients who underwent elective PCI were included from January 2012 to December 2018. The primary outcome was CA-AKI, defined as an increase in serum creatinine (SCr) ≥0.3 mg/dl or ≥50% than baseline SCr within 48 h after the PCI procedure. The secondary outcome was long-term mortality. All patients were classified into low- and high-SIS groups. Results: During hospitalization, 349 (6.1%) patients developed CA-AKI. Multivariate logistic regression analysis showed that patients in the high SIS group had a 1.47-fold higher risk of developing CA-AKI than those in the low SIS group [odds ratio (OR): 1.50, 95% confidence interval (CI): 1.12-2.01, P =0.006]. Furthermore, the SIS showed the greatest prediction performance for CA-AKI compared with other inflammatory hematological ratios. In the multivariate Cox regression analysis, the high SIS group was found to be closely associated with long-term mortality [hazard ratio (HR): 1.58, 95% CI: 1.26-1.97, P <0.001, vs low SIS group]. The Kaplan-Meier curve analysis also demonstrated a difference in long-term mortality between the two groups (Log rank test, P <0.001). Conclusion: The SIS was closely associated with CA-AKI and long-term mortality in patients after elective PCI. Thus, more attention should be paid to exploring the potential benefits of anti-inflammatory strategies in preventing CA-AKI and improving the prognosis of patients undergoing PCI.

Extranodal natural killer/T-cell lymphoma invading a patient's heart: A rare case report and literature review.

Extranodal NK/T-cell lymphoma (ENKTL) is a rare but aggressive subtype of non-Hodgkin lymphoma, which is derived from NK cells or T cells. There are very few cases of ENKTL invading the heart. Only 12 cases of ENKTL invading the heart have been reported in the English literature. Due to the rarity of this lymphoma, an effective therapeutic strategy has not been defined. Here, we present a case of a 51-year-old Chinese male with extranodal NK/T-cell lymphoma invading the heart and review the literature. The patient received a chemotherapy regimen of PD1 monoclonal antibody (Sintilimab) in combination with first-line P-Gemox. The patient survived for 2 months after diagnosis.

An Improved Chimp-Inspired Optimization Algorithm for Large-Scale Spherical Vehicle Routing Problem with Time Windows.

The vehicle routing problem with time windows (VRPTW) is a classical optimization problem. There have been many related studies in recent years. At present, many studies have generally analyzed this problem on the two-dimensional plane, and few studies have explored it on spherical surfaces. In order to carry out research related to the distribution of goods by unmanned vehicles and unmanned aerial vehicles, this study carries out research based on the situation of a three-dimensional sphere and proposes a three-dimensional spherical VRPTW model. All of the customer nodes in this problem were mapped to the three-dimensional sphere. The chimp optimization algorithm is an excellent intelligent optimization algorithm proposed recently, which has been successfully applied to solve various practical problems and has achieved good results. The chimp optimization algorithm (ChOA) is characterized by its excellent ability to balance exploration and exploitation in the optimization process so that the algorithm can search the solution space adaptively, which is closely related to its outstanding adaptive factors. However, the performance of the chimp optimization algorithm in solving discrete optimization problems still needs to be improved. Firstly, the convergence speed of the algorithm is fast at first, but it becomes slower and slower as the number of iterations increases. Therefore, this paper introduces the multiple-population strategy, genetic operators, and local search methods into the algorithm to improve its overall exploration ability and convergence speed so that the algorithm can quickly find solutions with higher accuracy. Secondly, the algorithm is not suitable for discrete problems. In conclusion, this paper proposes an improved chimp optimization algorithm (MG-ChOA) and applies it to solve the spherical VRPTW model. Finally, this paper analyzes the performance of this algorithm in a multi-dimensional way by comparing it with many excellent algorithms available at present. The experimental result shows that the proposed algorithm is effective and superior in solving the discrete problem of spherical VRPTW, and its performance is superior to that of other algorithms.

Rosmarinic Acid Prevents Cisplatin-Induced Liver and Kidney Injury by Inhibiting Inflammatory Responses and Enhancing Total Antioxidant Capacity, Thereby Activating the Nrf2 Signaling Pathway.

Drug-induced liver and kidney damage is an emergent clinical issue that should be addressed. Rosmarinic acid (RA) has obvious anti-inflammatory and antioxidant effects, so we evaluated the anti-inflammatory and antioxidant effects of RA pretreatment on serum and liver and kidney tissues of cisplatin (CP)-treated mice and explored the possible mechanisms. The results showed that RA pretreatment effectively downregulated the serum, liver, and kidney levels of ALT, AST, BUN, and CRE and the inflammatory factors IL-1ß, IL-6, and TNF-α, and simultaneously enhanced the total antioxidant capacity of the liver and kidney. RA pretreatment significantly reduced the levels of MPO, MDA, and NO in liver and kidney tissue, inhibited the mRNA expression of IL-1ß, IL-6, and TNF-α in liver and kidney tissue, activated the Nrf2 signaling pathway, and upregulated the mRNA expression of downstream target genes. Our findings show that RA could effectively prevent and alleviate acute liver and kidney injury caused by CP.

Preparation, Characterization and Pharmacokinetics of Tolfenamic Acid-Loaded Solid Lipid Nanoparticles.

The clinical use of nonsteroidal anti-inflammatory drugs is limited by their poor water solubility, unstable absorption, and low bioavailability. Solid lipid nanoparticles (SLNs) exhibit high biocompatibility and the ability to improve the bioavailability of drugs with low water solubility. Therefore, in this study, a tolfenamic acid solid lipid nanoparticle (TA-SLN) suspension was prepared by a hot melt-emulsification ultrasonication method to improve the sustained release and bioavailability of TA. The encapsulation efficiency (EE), loading capacity (LC), particle size, polydispersity index (PDI), and zeta potential of the TA-SLN suspension were 82.50 ± 0.63%, 25.13 ± 0.28%, 492 ± 6.51 nm, 0.309 ± 0.02 and -21.7 ± 0.51 mV, respectively. The TA-SLN suspension was characterized by dynamic light scattering (DLS), fluorescence microscopy (FM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared (FT-IR) spectroscopy. The TA-SLN suspension showed improved sustained drug release in vitro compared with the commercially available TA injection. After intramuscular administration to pigs (4 mg/kg), the TA-SLN suspension displayed increases in the pharmacokinetic parameters Tmax, T1/2, and MRT0-∞ by 4.39-, 3.78-, and 3.78-fold, respectively, compared with TA injection, and showed a relative bioavailability of 185.33%. Thus, this prepared solid lipid nanosuspension is a promising new formulation.

A Case Study of Grassroots Water Conservancy Services Evaluation and Obstacle Factors Diagnosis Based on Gray Correlation-TOPSIS Model in Hunan Province, China.

Based on the evaluation model of the gray correlation-TOPSIS method, this paper examines the index system of grass-roots water conservancy services in Hunan Province, China. This paper aims at the present situation of grassroots water conservancy in Hunan province, which assisted it in developing grassroots water conservancy services. The evaluation indicators include five criteria levels (institutional staffing, personnel quality, management level, public policy and service capacity) and twenty-four indicator levels. In this paper, the weight calculation method combined with an analytic hierarchy process and an entropy weight method, as well as quantitative and qualitative methods, was used to conduct an empirical study on the basic water conservancy service level of Hunan Province in 2020. The results classify grassroots water services in Hunan Province into three levels. By fitting the GDP of cities and prefectures with the comprehensive closeness, we conclude that there is considerable convergence between the grassroots water conservancy service level of Hunan Province and its local economic level. The more developed the economy, the higher the grassroots water conservancy service level. In addition, through obstacle factor analysis, the main constraints of grassroots water conservancy in various cities and prefectures are obtained. Therefore, the grassroots water conservancy service's ability can be comprehensively improved from three aspects: serviceability, capital investment, and talent construction. This indicator system can promote the overall governance capacity of grassroots water conservancy in the future development of cities and prefectures, and it can also provide Hunan with experience and case examples for the implementation of rural revitalization.

Case Report: A Rare Syncope Case Caused by Abernethy II and a Review of the Literature.

Background: Abernethy malformation is an extremely rare anomaly of the splanchnic venous system, and only 2 cases that manifested as syncope had been reported previously. Case Presentation: A 24-year-old male had a 15-year history of jaundice and was in long-term use of hepatoprotective drugs. He was admitted for complaint of syncope. He underwent a series of examinations and cardiac ultrasound showed that his pulmonary artery pressure was elevated. Further imaging revealed the absence of intrahepatic portal veins. His blood ammonia was significantly increased. All signs and symptoms pointed to an Abernethy diagnosis. He was finally diagnosed as having Abernethy type II. He was discharged after 17 days of in-hospital treatment with sildenafil (50 mg/day) and ornithine aspartate (20 g/day). Conclusion: We now report this rare case of syncope that is caused by Abernethy malformation. As a typically pediatric disease, it was not identified in this patient until adulthood due to long-term treatment for jaundice and liver cirrhosis. Furthermore, we present a review of portosystemic shunts previously reported in the literature.

Hypoglycemic effects of intraluminal intestinal electrical stimulation in healthy volunteers.

BACKGROUND: Intestinal electrical stimulation (IES) has been shown to delay gastric emptying and reduce nutrient absorption in humans. The aim of this study was to investigate the effect of IES using an intraluminal method on postprandial blood glucose. METHODS: An oral glucose tolerance test with 150 g of glucose was performed in 10 healthy volunteers with and without IES (13 pulses/min, 300 ms and 5 mA). An intraluminal catheter with a pair of ring electrodes was incubated into the duodenum under endoscopy and used for IES. Gastric emptying was performed simultaneously using an established ultrasonic technique. RESULTS: (1) IES significantly decreased the postprandial glucose level from 15 min to 90 min after the glucose load. (2) The serum insulin level at 30 min but not other times after the meal was lower in the IES session than that in the control session (p = 0.06). (3) The half-time of gastric emptying with IES was increased from 27 ± 4.8 min in the control session to 36 ± 8.5 min with IES (p < 0.01). (4) The symptoms score of dyspepsia were almost the same between the two sessions except that IES induced a slightly higher nausea symptom score. CONCLUSIONS: IES decreases postprandial blood glucose possibly by delaying gastric emptying and other unknown mechanisms and the intraluminal method of IES may serve as an excellent screening and research tool for various applications of IES. Further clinical studies are needed to explore therapeutic potentials of IES for diabetes.