Serum short-chain fatty acids and its correlation with motor and non-motor symptoms in Parkinson's disease patients.

BACKGROUND: Parkinson's disease (PD) is associated with enteric nervous system dysfunction and gut microbiota dysbiosis. Short-chain fatty acids (SCFAs), derived from gut microbiota, are supposed to anticipate PD pathogenesis via the pathway of spinal cord and vagal nerve or the circulatory system. However, the serum concentration of SCFAs in PD patients is poorly known. This study aims to investigate the exact level of SCFAs in PD patients and its correlation with Parkinson's symptoms. METHODS: 50 PD patients and 50 healthy controls were recruited, and their demographic and clinical characteristics were collected. The serum concentration of SCFAs was detected using a gas chromatography-mass spectrometer. SCFAs were compared between PD and control groups. The correlation between serum SCFAs and Parkinson's symptoms and the potential effects of medications on the serum SCFAs was analyzed. RESULTS: Serum propionic acid, butyric acid and caproic acid were lower, while heptanoic acid was higher in PD patients than in control subjects. However, only the serum level of propionic acid was correlated with Unified Parkinson's Disease Rating Scale (UPDRs) part III score (R = -0.365, P = 0.009), Mini-mental State Examination (MMSE) score (R = -0.416, P = 0.003), and Hamilton Depression Scale (HAMD) score (R = 0.306, P = 0.03). There was no correlation between other serum SCFAs and motor complications. The use of trihexyphenidyl or tizanidine increased the serum concentration of propionic acid. CONCLUSIONS: Serum SCFAs are altered in PD patients, and the decrease of serum propionic acid level is correlated with motor symptoms, cognitive ability and non-depressed state. Thus, the gut microbial-derived SCFAs potentially affect Parkinson's symptoms through the blood circulation. Propionic acid supplementation might ameliorate motor and non-motor symptoms of PD patients, although clinical trials are needed to test this hypothesis.

Synthesis and biological evaluation of novel SIPI-7623 derivatives as farnesoid X receptor (FXR) antagonists.

Most of reported steroidal FXR antagonists are restricted due to low potency. We described the design and synthesis of novel nonsteroidal scaffold SIPI-7623 derivatives as FXR antagonists. The most potent compound A-11 (IC50 = 7.8 ± 1.1 µM) showed better activity compared to SIPI-7623 (IC50 = 40.8 ± 1.7 µM) and guggulsterone (IC50 = 45.9 ± 1.1 µM). Docking of A-11 in FXR's ligand-binding domain was also studied.

Traditional Chinese medicine prescription Shenling BaiZhu powder to treat ulcerative colitis: Clinical evidence and potential mechanisms.

Ulcerative colitis (UC), characterized by syndromes including abdominal pain, bloody stool, diarrhea, weight loss, and repeated relapse, is a non-specific inflammatory intestinal disease. In recent years, with the changing dietary habits in China, the incidence of UC has shown an upward trend. UC belongs to the category of recorded as "diarrhea," "chronic dysentery," and "hematochezia" in traditional Chinese medicine (TCM), and Shenling BaiZhu powder (SLBZP) is one of the most effective and commonly used prescriptions. In this review, we aim to systematically summarize the clinical application and pharmacological mechanism of SLBZP in the treatment of UC to provide a theoretical basis for its clinical use and experimental evaluation of SLBZP. Our results showed that both SLBZP and SLBZP in combination with chemical drugs, have a significant therapeutic effect against UC with few adverse reactions. Furthermore, combined therapy was better than western medicine. Further, pathophysiological studies indicated that SLBZP has anti-inflammatory, immunomodulatory, antioxidant effects, regulation relative cell signal transduction and regulation of gut microbiota. Although evidence suggests superior therapeutic efficacy of SLBZP for treating UC and the relative mechanism has been studied extensively, various shortcomings limit the existing research on the topic. There is a lack of UC animal models, especially UC with TCM syndromes, with no uniform standard and certain differences between the animal model and clinical syndrome. The dosage, dosage form, and therapeutic time of SLBZP are inconsistent and lack pharmacological verification, and clinical trial data are not detailed or sufficiently rigorous. In addition, SLSZP is composed of multiple Chinese drugs that contain massive numbers of ingredients and which or several components contribute to therapeutic effects. How they work synergistically together remains unknown. Therefore, on the one hand, large sample prospective cohort studies to clarify the clinical efficacy and safety of SLBZP in the treatment of UC are needed. In contrast, researchers should strengthen the study of the molecular biological mechanism of active ingredients and its synergistic actions, clarifying the mechanism of SLBZP in treating UC by multi-component, multi-target, and multi-pathway.

A survey on the safety of the SARS-CoV-2 vaccine among a population with stroke risk in China.

Background: The safety of the COVID-19 vaccine in patients at stroke risk is poorly understood. Methods: A survey was conducted on risk factors related to stroke and adverse reactions to vaccines. The participants were divided into low-, medium-, and high-risk groups, according to the stroke risk scorecard recommended by the Stroke Prevention and Control Engineering Committee of the National Health and Family Planning Commission. Factors associated with adverse reactions were analyzed. Reasons for non-vaccination and the aggravation of underlying diseases after vaccination were investigated. Results: 1747 participants participated (138 unvaccinated) and 36.8, 22.1, 41.1% of the vaccinated participants had low, medium, high risk of stroke, respectively. The incidence of adverse reactions after the first and second injection was 16.6, 13.7%, respectively. There was no difference in the incidence of adverse reactions among different risk groups. Sex, vaccine type, sleep quality, worry of adverse reactions, age, and education level were significantly related to adverse reactions to vaccination. The most popular reason for non-vaccination for medium- or high risk-participants was the aggravation of the existing disease. Only 0.3% of vaccinated participants reported slight changes in blood pressure, sugar levels, and lipid levels. No aggravation of stroke sequelae, atrial fibrillation, or transient ischemic attack was reported. Conclusions: Vaccination against COVID-19 (inactive virus) is safe for people at risk of stroke when the existing disease condition is stable. It is suggested to strengthen vaccine knowledge and ensure good sleep before vaccination.

Therapy Management of Metabolic Disorder Comorbidity With Depression.

Depression is a common disease that seriously endangers the physical and mental health of human beings, and it often coexists with other metabolic disorders such as diabetes and cancer. There have been endless reports on the mechanism, prevention, and cure of comorbidity because of its high incidence and poor prognosis and the increased burden on the family and society. There may be a specific comorbid basis and causal relationship between depression and metabolic diseases. Depression in patients with metabolic disorders can be effectively alleviated through psychotherapy and medication. The timely and effective treatment of depression can significantly improve the quality of life of patients with metabolic disorders, reduce their psychological burden, and promote the effective treatment of metabolic diseases. This study reorganized the research progress on the management of metabolic disorder comorbidity with depression.

Study on the Molecular Basis of Huanglian Jiedu Decoction Against Atopic Dermatitis Integrating Chemistry, Biochemistry, and Metabolomics Strategies.

Atopic dermatitis (AD) is a common chronic relapsing skin inflammation, which severely affect the quality of life of patients. Inhibiting itching and enhancing immunity to mitigate scratching are key elements in the fight against AD. Huanglian Jiedu decoction (HLJDD) has multiple pharmacological effects in the treatment of AD. However, the effective ingredients and underlying molecular mechanisms have not yet been fully explored. Thus, this study integrates chemistry, biochemistry, and metabolomics strategies to evaluate the active substance basis of HLJDD against AD. First, HLJDD was split to five fractions (CPF, 40AEF, 90AEF, PEF and WEF) and 72 chemical components were identified. NSD (Non-similarity degree) among the different fractions showed significant chemical differences (>81%). Interleukin IL-13, IL-17A, IL-3, IL-31, IL-33, IL4, IL-5, TSLP, IgE, and histamine in the serum, and IL-4Rα, JAK1, and HRH4 levels in skin, participating in inhibiting itching and regulating immunity signaling, were found to be restored to varying degrees in AD treating with HLJDD and its fractions, especially 40AEF and CPF. Untargeted metabolomics analysis demonstrated that forty metabolites were differential metabolites in plasma between the HLJDD-treated group and the AD group, involving in histidine metabolism, arginine biosynthesis, pyrimidine metabolism, and so on. Further, targeted metabolomics analysis revealed that eleven differential metabolites, associating with physiological and biochemical indices, were significant improved in the HLJDD and its fractions groups. In conclusion, HLJDD exhibited anti-AD effects by inhibiting itching and enhancing immunity, which in turn regulating the levels of relative metabolites, and CPF and 40AEF were considered the most important components of HLJDD.

Population pharmacokinetic modeling and clinical application of vancomycin in Chinese patients hospitalized in intensive care units.

Management of vancomycin administration for intensive care units (ICU) patients remains a challenge. The aim of this study was to describe a population pharmacokinetic model of vancomycin for optimizing the dose regimen for ICU patients. We prospectively enrolled 466 vancomycin-treated patients hospitalized in the ICU, collected trough or approach peak blood samples of vancomycin and recorded corresponding clinical information from July 2015 to December 2017 at Tai Zhou Hospital of Zhejiang Province. The pharmacokinetics of vancomycin was analyzed by nonlinear mixed effects modeling with Kinetica software. Internal and external validation was evaluated by the maximum likelihood method. Then, the individual dosing regimens of the 92 patients hospitalized in the ICU whose steady state trough concentrations exceeded the target range (10-20 µg/ml) were adjusted by the Bayes feedback method. The final population pharmacokinetic model show that clearance rate (CL) of vancomycin will be raised under the conditions of dopamine combined treatment, severe burn status (Burn-S) and increased total body weight (TBW), but reduced under the conditions of increased serum creatinine (Cr) and continuous renal replacement therapy status; Meanwhile, the apparent distribution volume (V) of vancomycin will be enhanced under the terms of increased TBW, however decreased under the terms of increased age and Cr. The population pharmacokinetic parameters (CL and V) according to the final model were 3.16 (95%CI 2.83, 3.40) L/h and 60.71 (95%CI 53.15, 67.46). The mean absolute prediction error for external validation by the final model was 12.61% (95CI 8.77%, 16.45%). Finally, the prediction accuracy of 90.21% of the patients' detected trough concentrations that were distributed in the target range of 10-20 µg/ml after dosing adjustment was found to be adequate. There is significant heterogeneity in the CL and V of vancomycin in ICU patients. The constructed model is sufficiently precise for the Bayesian dose prediction of vancomycin concentrations for the population of ICU Chinese patients.

Short- and long-term outcomes of laparoscopic versus open surgery for rectal cancer: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: The present meta-analysis aimed to evaluate the short- and long-term outcomes of laparoscopic surgery (LS) versus open surgery (OS) for rectal cancer. METHODS: PubMed, Web of Science, and Cochrane Library, were searched for eligible randomized controlled trials (RCTs) published up to June 2017. Operation related index, postoperative complication, and long-term survival rate and disease-free survival rate were evaluated by meta-analytical techniques. RESULT: Nine RCTs enrolling 4126 patients were included in the present meta-analysis. Compared to OS, LS had similar positive circumferential resection margin (CRM) and number of lymph nodes extracted (LNE) as well as long term 5 years survival rate and disease-free survival rate, but of which the risk tendency was higher in LS group. The short-term outcomes of major and total postoperative complication were lower in LS group. CONCLUSIONS: LS for rectal cancer was as safe and effective as OS in terms of long-term outcomes, but with lower postoperative complication.