Effects of mindful breathing training combined with diary-based rehabilitation guidance in lung cancer patients undergoing surgery: A randomized controlled trial.

BACKGROUND AND PURPOSE: Lung cancer surgery patients experience severe physical and mental symptoms, which seriously affect their quality of life and prognosis. Mindful breathing training is a promising strategy to improve their symptoms, but its effectiveness is affected by training compliance, and diary-based rehabilitation instruction has been shown to help improve training compliance. Therefore, the aim of this study was to evaluate the effects of mindful breathing training combined with diary-based rehabilitation guidance on improving perioperative outcomes in lung cancer surgery patients. MATERIALS AND METHODS: This single-center, assessor-blinded, prospective, three-arm randomized controlled trial was conducted from November 1, 2021 to November 1, 2022. Patients diagnosed with primary non-small cell lung cancer and scheduled for thoracoscopic surgery were randomly allocated to the combined intervention group, the mindful breathing group or the control group, with 34 patients in each group. The control group received routine care, while the mindful breathing group received mindful breathing training and routine care. The combined intervention group received both mindful breathing training and diary-based rehabilitation guidance, along with routine care. RESULTS: The per-protocol analysis revealed that patients in the mindful breathing group experienced statistically significant improvements in dyspnea, fatigue and anxiety. Patients in the combined intervention group had statistically significant improvements in dyspnea, fatigue, anxiety, depression, exercise self-efficacy and training compliance. CONCLUSION: This study provides evidence that mindful breathing training combined with diary-based rehabilitation guidance can be effective in improving perioperative outcomes in lung cancer patients. It can be applied in clinical practice in the future.

Nonpharmacological interventions for cancer-related fatigue: A literature review.

Cancer-related fatigue (CRF) is a prevalent and debilitating side effect of cancer treatment that can persist for years posttreatment, significantly impacting patients' quality of life. Given the limited efficacy of pharmacological treatments, nonpharmacological interventions are gaining attention as effective management strategies for CRF. This review aims to provide an overview of the most common nonpharmacological interventions for CRF management, including exercise therapies, psychosocial interventions, sensory art therapy, light therapy, nutritional management, traditional Chinese medicine therapies, sleep management, combination therapy, and health education. By synthesizing the findings of high-quality literature, this review presents the definition of each therapy, along with their advantages and disadvantages in treating patients with CRF. Additionally, it addresses the role of oncology nurses in the nonpharmacological management of CRF. In summary, this review aims to inform oncology nurses about the prevalent nonpharmacological interventions for CRF and explore their clinical application to facilitate the development of effective CRF management strategies in clinical practice.

Integrative Single-Cell and Bulk Transcriptomes Analyses Identify Intrinsic HNSCC Subtypes with Distinct Prognoses and Therapeutic Vulnerabilities.

PURPOSE: Tumor heterogeneity in head and neck squamous cell carcinoma (HNSCC) profoundly compromises patient stratification, personalized treatment planning, and prognostic prediction, which underscores the urgent need for more effective molecular subtyping for this malignancy. Here, we sought to define the intrinsic epithelial subtypes for HNSCC by integrative analyses of single-cell and bulk RNA sequencing datasets from multiple cohorts and assess their molecular features and clinical significance. EXPERIMENTAL DESIGN: Malignant epithelial cells were identified from single-cell RNA sequencing (scRNA-seq) datasets and subtyped on the basis of differentially expressed genes. Subtype-specific genomic/epigenetic abnormalities, molecular signaling, genetic regulatory network, immune landscape, and patient survival were characterized. Therapeutic vulnerabilities were further predicted on the basis of drug sensitivity datasets from cell lines, patient-derived xenograft models, and real-world clinical outcomes. Novel signatures for prognostication and therapeutic prediction were developed by machine learning and independently validated. RESULTS: Three intrinsic consensus molecular subtypes (iCMS1-3) for HNSCC were proposed from scRNA-seq analyses and recapitulated in 1,325 patients from independent cohorts using bulk-sequencing datasets. iCMS1 was characterized by EGFR amplification/activation, stromal-enriched environment, epithelial-to-mesenchymal transition, worst survival, and sensitivities to EGFR inhibitor. iCMS2 was featured by human papillomavirus-positive oropharyngeal predilection, immune-hot, susceptibilities to anti-PD-1, and best prognosis. Moreover, iCMS3 displayed immune-desert and sensitivities to 5-FU and MEK, STAT3 inhibitors. Three novel, robust signatures derived from iCMS subtype-specific transcriptomics features were developed by machine learning for patient prognostication and cetuximab and anti-PD-1 response predictions. CONCLUSIONS: These findings reiterate molecular heterogeneity of HNSCC and advantages of scRNA-seq in pinpointing cellular diversities in complex cancer ecosystems. Our HNSCC iCMS regime might facilitate accurate patient stratification and individualized precise treatment.

L-Ascorbic Acid 2-Phosphate Attenuates Methylmercury-Induced Apoptosis by Inhibiting Reactive Oxygen Species Accumulation and DNA Damage in Human SH-SY5Y Cells.

Methylmercury (MeHg) is a toxin that causes severe neuronal oxidative damage. As vitamin C is an antioxidant well-known to protect neurons from oxidative damage, our goal was to elucidate its protective mechanism against MeHg-induced oxidative stress in human neuroblastomas (SHSY5Y). We treated cells with MeHg, L-ascorbic acid 2-phosphate (AA2P), or both, and used MTT, flow cytometry, and Western blot analyses to assess cell damage. We found that MeHg significantly decreased the survival rate of SH-SY5Y cells in a time- and dose-dependent manner, increased apoptosis, downregulated PAR and PARP1 expression, and upregulated AIF, Cyto C, and cleaved Caspase-3 expression. A time course study showed that MeHg increased reactive oxygen species (ROS) accumulation; enhanced apoptosis; increased DNA damage; upregulated expression ofγH2A.X, KU70, 67 and 57 kDa AIF, CytoC, and cleaved Caspase-3; and downregulated expression of 116 kDa PARP1, PAR, BRAC1, and Rad51. Supplementation with AA2P significantly increased cell viability and decreased intrinsic ROS accumulation. It also reduced ROS accumulation in cells treated with MeHg and decreased MeHg-induced apoptosis. Furthermore, AA2P conversely regulated gene expression compared to MeHg. Collectively, we demonstrate that AA2P attenuates MeHg-induced apoptosis by alleviating ROS-mediated DNA damage and is a potential treatment for MeHg neurotoxicity.

Investigation of Ultrafast Configurational Photoisomerization of Bilirubin Using Femtosecond Stimulated Raman Spectroscopy.

Phototherapy is an efficient and safe way to reduce high levels of free 4Z,15Z-bilirubin (ZZ-BR) in the serum of newborns. The success of BR phototherapy lies in photoinduced configurational and structural isomerization processes that form excretable isomers. However, the physical picture of photoinduced photoisomerization of ZZ-BR is still unclear. Here, we strategically implement tunable femtosecond stimulated Raman spectroscopy and several time-resolved electronic spectroscopies, assisted by quantum chemical calculations, to dissect the detailed primary configurational isomerization dynamics of free ZZ-BR in organic solvents. The results of this study demonstrate that upon photoexcitation, ultrafast configurational isomerization proceeds by a volume-conserving "hula twist", followed by intramolecular hydrogen-bond distortion and large-scale rotation of the two dipyrrinone halves of the ZZ-BR isomer in a few picoseconds. After that, most of the population recovers back to ZZ-BR, and a very small amount is converted into stable BR isomers via structural isomerization.

Berberine a traditional Chinese drug repurposing: Its actions in inflammation-associated ulcerative colitis and cancer therapy.

Berberine (BBR), an isoquinoline alkaloid extracted from Coptidis Rhizoma, has a long history of treating dysentery in the clinic. Over the past two decades, the polytrophic, pharmacological, and biochemical properties of BBR have been intensively studied. The key functions of BBR, including anti-inflammation, antibacterial, antioxidant, anti-obesity, and even antitumor, have been discovered. However, the underlying mechanisms of BBR-mediated regulation still need to be explored. Given that BBR is also a natural nutrition supplement, the modulatory effects of BBR on nutritional immune responses have attracted more attention from investigators. In this mini-review, we summarized the latest achievements of BBR on inflammation, gut microbes, macrophage polarization, and immune responses associated with their possible tools in the pathogenesis and therapy of ulcerative colitis and cancer in recent 5 years. We also discuss the therapeutic efficacy and anti-inflammatory actions of BBR to benefit future clinical applications.

Diprenylated flavonoids from licorice induce death of SW480 colorectal cancer cells by promoting autophagy: Activities of lupalbigenin and 6,8-diprenylgenistein.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is a well-known herbal medicine, and we previously found that several licorice prenylated flavonoids could cause death of SW480 colorectal cancer cells by promoting autophagy. Given many kinds of prenylated flavonoids in licorice, the activities of other compounds deserve further investigation. In addition, the contribution of isoprenyl groups on the autophagy promotion activities has not been clarified. AIM OF THE STUDY: This study aimed to investigate whether lupalbigenin (LPB) and 6,8-diprenylgenistein (DPG), two licorice diprenylated flavonoids, could induce autophagic cell death of SW480 cells, and clarify the contribution of isoprenyl groups. MATERIALS AND METHODS: Cytotoxic activities of LPB and DPG were tested by using an MTT method, and apoptosis induction effects were evaluated by PI-Annexin V staining-based flow cytometry and protein levels of caspase-3 and PARP-1. Autophagy promotion effects of LPB and DPG were assessed by protein levels of LC3, p62, Akt and mTOR as well as number of autophagosomes in cells, and autophagy inhibitor chloroquine (CQ) was involved to identify the role of autophagy on LPB or DPG-caused death of SW480 cells. In addition, two groups of structurally similar diprenylated, mono-prenylated and free flavonoids were obtained from licorice, which were used to investigate the contribution of isoprenyl groups on their autophagy promotion activities. RESULTS: Both LPB and DPG significantly induced apoptosis of SW480 cells with strong cytotoxic activities, and meanwhile, they also promoted autophagy probably through the Akt/mTOR signaling pathway. Further studies indicated that LPB and DPG could induce autophagic cell death of SW480 cells. Moreover, isoprenyl groups contributed mainly to the cytotoxic and autophagy promotion activities of licorice prenylated flavonoids. CONCLUSION: This study reported for the first time that licorice diprenylated flavonoids LPB and DPG induced death of SW480 cells by promoting autophagy, which was mainly attributed to the isoprenyl groups. The results provided theoretical basis for researches on anti-colorectal cancer drugs and their structural modification.

Three-dimensional visualization of electroacupuncture-induced activation of brown adipose tissue via sympathetic innervation in PCOS rats.

BACKGROUND: Low-frequency electroacupuncture (EA) has been shown to ameliorate obesity and reproductive dysfunctions in patients with polycystic ovary syndrome (PCOS), and further explorations in PCOS-like rats showed that EA could affect white adipose tissue. However, the function and neuromodulation of brown adipose tissue (BAT) in PCOS and after EA treatment have remained unknown. The present study focused on the role of BAT in PCOS-like rats and its relationship with EA and characterized the three-dimensional (3D) innervation of BAT associated with activation molecules. METHODS: Female rats (21 days old) were implanted with dihydrotestosterone or fed with a high fat diet to establish PCOS-like and obesity models, respectively, and then EA treatment at "Guilai" (ST 29) and "Sanyinjiao" (SP 6) was carried out for 4 weeks. In the present study, morphological analysis, 3D imaging, molecular biology, and other experimental techniques were used to study the sympathetic nerves and activity of BAT. RESULTS: PCOS-like rats showed both obvious weight gain and reproductive dysfunction, similar to what was seen in obese rats except for the absence of reproductive dysfunction. The body weight gain was mainly caused by an increase in white adipose tissue, and there was an abnormal decrease in BAT. Because both the lipid metabolism and reproductive disorders could be improved with bilateral EA at "Guilai" (ST 29) and "Sanyinjiao" (SP 6), especially the restoration of BAT, we further investigated the neuromodulation and inflammation in BAT and identified the sympathetic marker tyrosine hydroxylase as one of the key factors of sympathetic nerves. Modified adipo-clearing technology and 3D high-resolution imaging showed that crooked or dispersed sympathetic nerves, but not the twisted vasculature, were reconstructed and associated with the activation of BAT and are likely to be the functional target for EA treatment. CONCLUSION: Our study highlights the significant role of BAT and its sympathetic innervations in PCOS and in EA therapy.

Prenylated phenolic compounds from licorice (Glycyrrhiza uralensis) and their anti-inflammatory activity against osteoarthritis.

Osteoarthritis is a significant driver of disability in the elderly with increasing prevalence, and inflammation plays a vital role on its etiology. Licorice is commonly used as a traditional Chinese medicine or food additive, and its prenylated phenolic compounds were recently reported to be able to inhibit osteoarthritis with anti-inflammatory activity. In order to explore more anti-osteoarthritic prenylated phenolic compounds from licorice, we isolated ten compounds (1-10), with three new ones (1-3), from the ethyl acetate extract of Glycyrrhiza uralensis. Compound 2 (glycyuralin R) was a racemic 3-phenoxy-chromanone, and we achieved its chiral separation for the first time. Compounds 1, 2, 7 and 8 showed significant NO inhibitory ability in IL-1ß-stimulated mouse primary chondrocytes, and we further confirmed the anti-inflammatory activity of 1 (glycyuralin Q) by evaluating its effect on osteoarthritis-related iNOS, COX-2, TNF-α, IL-6, MMP3, MMP13 and NF-κB based on various experimental methods. These results clarified the potential of several prenylated phenolic compounds, especially 1 in licorice, as the lead compounds for osteoarthritis.

Impact of prolonged withering on phenolic compounds and antioxidant capability in white tea using LC-MS-based metabolomics and HPLC analysis: Comparison with green tea.

Contents of 20 bioactive compounds in 12 teas produced in Xinyang Region were determined by high performance liquid chromatography. Ultra-high performance liquid chromatography-quadrupole time of flight-mass spectrometry was developed for untargeted metabolomics analysis. Antioxidant activities were measured by 4 various assays. Those teas could be completely divided into green and white tea through principal component analysis, hierarchical cluster analysis and orthonormal partial least squares-discriminant analysis (R2Y = 0.996 and Q2 = 0.982, respectively). The prolonged withering generated 472 differentiated metabolites between white and green tea, prompted significant decreases (variable importance in the projection > 1.0, p-value < 0.05 and fold change > 1.50) of most catechins and 8 phenolic acids to form 4 theaflavins, and benefited for the accumulation of 17 flavonoids and flavonoid glycosides, 8 flavanone and their derivatives, 20 free amino acids, 12 sugars and 1 purine alkaloid. Additionally, kaempferol and taxifolin contributed to 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging ability of white tea.

Effects of early-life zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns.

OBJECTIVE: To investigate the effect of maternal zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns. METHODS: Pregnant rats were divided into zinc adequate (ZA), zinc deficient (ZD), and paired fed (PF) groups. Serum zinc contents and AKP activity in mother rats and offspring at P21 (end of lactation) and P60 (weaned, adult) were detected. Cognitive ability of offspring at P21 and P60 were determined by Morris water maze. The expression of proteins including DNMT3a, DNMT1, GADD45ß, MeCP2 and BDNF in the offspring hippocampus were detected by Western-blot. The methylation status of BDNF promoter region in hippocampus of offspring rats was detected by MS-qPCR. RESULTS: Compared with the ZA and PF groups, pups in the ZD group had lower zinc levels and AKP activity in the serum, spent more time finding the platform and spent less time going through the platform area. Protein expression of DNMT1 and GADD45b were downregulated in the ZD group during P0 and P21 but not P60 compared with the ZA and PF group, these results were consistent with a reduction in BDNF protein at P0 (neonate), P21. However, when pups of rats in the ZD group were supplemented with zinc ion from P21 to P60, MeCP2 and GADD45b expression were significantly downregulated compared with the ZA and PF group. CONCLUSION: Post-weaning zinc supplementation may improve cognitive impairment induced by early life zinc deficiency, whereas it may not completely reverse the abnormal expression of particular genes that are involved in DNA methylation, binding to methylated DNA and neurogenesis.

Comparison of efficacy and safety of His-Purkinje system pacing versus cardiac resynchronisation therapy in patients with pacing-induced cardiomyopathy: protocol for a randomised controlled trial.

INTRODUCTION: Recent studies have shown that the His-Purkinje system pacing (HPSP) can achieve electrocardiomechanical synchronisation, and thus improve cardiac function. For patients with pacing-induced cardiomyopathy (PICM) who should be treated with pacemaker upgrade, the HPSP is a viable alternative to cardiac resynchronisation therapy (CRT). However, no randomised controlled trial has been performed to evaluate the efficacy and safety of HPSP in patients with PICM. The present study compared the efficacy and safety of HPSP with that of traditional CRT in the treatment of patients with PICM. METHODS AND ANALYSIS: This study is a single-centre, randomised controlled non-inferiority trial. This trial was carried out at the cardiac centre of Beijing Anzhen Hospital. A total of 46 patients with PICM who needed pacemaker upgrade treatment between January 2022 and December 2023 will be enrolled in this study. Patients will be randomised into an investigational group (HPSP) and a control group (CRT) at a 1:1 ratio. The primary outcome is the duration of QRS complex (QRS width), and the secondary outcomes are NT-proBNP (N terminal pro B type natriuretic peptide), C reactive protein, the number of antibiotics used, left ventricular ejection fraction, end systolic volume, end diastolic volume, the hospitalisation duration, the incidence of postoperative infection, pacemaker parameters (threshold, sensing and impedance), the 6-minute walking test, and quality of life (36-Item Short Form Survey scale), all-cause mortality, cardiovascular death, heart failure-related rehospitalisation rate, other rehospitalisation rates, major complication rates and procedure costs. ETHICS AND DISSEMINATION: This study has been approved by the Beijing Anzhen Hospital Medical Ethics Committee (No. 2020043X). TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2000034265).

Effects of dietary betaine supplementation on biochemical parameters of blood and testicular oxidative stress in Hu sheep.

Betaine, a highly valuable feed additive, has been observed to alter the distribution of protein and fat in the bodies of ruminants and to exhibit strong antioxidant properties. However, the effects of dietary betaine supplementation on the biochemical parameters of blood and on testicular oxidative stress remain unknown. This study aimed to investigate the effects of dietary betaine supplementation on lipid metabolism, immunity, and testicular oxidative status in Hu sheep. Experimental sheep (n=3, three sheep per group) were fed betaine-containing diets, a basal diet supplemented with 0 g/day (control group), 1 g/day (B1), and 3 g/day betaine (B2). There were no differences in the serum concentrations of triglycerides and cholesterol in Hu sheep receiving diets supplemented with betaine. The ratio of basophils significantly increased in the B1 and B2 groups. ELISA (enzyme-linked immunosorbent assay) results showed that testicular superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity were significantly higher, whereas malondialdehyde (MDA) content significantly decreased, after feeding betaine-supplemented diets. qPCR results showed that the mRNA expression levels of CAT, SOD2, and GSH-Px were significantly upregulated in both the B1 and B2 groups compared to those in the control group. Furthermore, the expression of proliferating cell nuclear antigen (PCNA) was significantly lower in the testes of betaine-treated Hu sheep than in the control group. Moreover, LKB1 (liver kinase B1) expression significantly increased, and mRNA expression of AMPK (AMP-activated serine/threonine protein kinase) significantly decreased in the B1 group. The relative gene expression of mTOR (mechanistic target of rapamycin) was significantly higher in the B2 group than in the control group. RAPTOR expression significantly increased in the B1 group. Western blot revealed that the ratio of P-mTOR and mTOR significantly increased after feeding betaine-supplemented diets. In conclusion, betaine supplementation improved serum lipid metabolism, immune response, and increased the testicular antioxidant capacity of Hu sheep, which might be regulated via mTOR signaling pathway.

Cardiac resynchronization therapy in heart failure patients: tough road but clear future.

Cardiac resynchronization therapy (CRT) based on biventricular pacing (BVP) is an invaluable intervention currently used in heart failure (HF) patients. The therapy involves electromechanical dyssynchrony, which can not only improve heart function and quality of life but also reduce hospitalization and mortality rates. However, approximately 30% to 40% of patients remain unresponsive to conventional BVP in clinical practice. In the recent years, extensive research has been employed to find a more physiological approach to cardiac resynchronization. The His-Purkinje system pacing (HPSP) including His bundle pacing (HBP) and left bundle branch area pacing (LBBaP) may potentially be the future of CRT. These technologies present various advantages including offering an almost real physiological pacing, less complicated procedures, and economic feasibility. Additionally, other methods, such as isolated left-ventricular pacing and multipoint pacing, may in the future be important but non-mainstream alternatives to CRT because currently, there is no strong evidence to support their effectiveness. This article reviews the current situation and latest progress in CRT, explores the existing technology, and highlights future prospects in the development of CRT.

Strategy for Highly Efficient Radioprotection by a Selenium-Containing Polymeric Drug with Low Toxicity and Long Circulation.

Because of the rapid development and extensive use of nuclear technology, ionizing radiation has become a large threat to human health. Until now, there has been no practicable radioprotector for routine clinical application because of severe side effects, high toxicity, and short elimination half-life. Herein, we develop a highly efficient radioprotection strategy using a selenium-containing polymeric drug with low toxicity and long circulation by removing reactive oxygen species (ROSs). The selenium-containing polymeric drug is prepared by copolymerization of vinyl phenylselenides (VSe) and N-(2-hydroxyethyl) acrylamide (HEA). The in vitro radioprotective efficacy of the polymeric drug is increased by 40% with lower cytotoxicity compared with the small-molecular VSe monomer. Importantly, the radioprotection activity of the polymeric drug shows more remarkable effects both in cell culture and mice model compared to the commercially available drug ebselen and also exhibits a much longer retention time in blood (half-life ∼ 10 h). This work may unfold a new area for highly efficient radioprotection by polymeric drugs instead of small-molecular agents.

Total glucosides of paeony (TGP) alleviates constipation and intestinal inflammation in mice induced by Sjögren's syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Sjögren's syndrome (SS) is an autoimmune disease and can cause gastrointestinal disorders such as constipation and intestinal inflammation. As a kind of medicinal material, Paeonia lactiflora Pall has a variety of pharmacological effects, and it is also an indispensable component in many pharmaceutical preparations, which has been widely concerned by the medical and pharmaceutical circles. Total glucosides of paeony (TGP) is a mixture of biologically active compounds extracted from the root of Paeonia lactiflora Pall and has therapeutic effects on a variety of autoimmune diseases. AIM OF THE STUDY: To investigate the therapeutic effect of TGP on constipation and intestinal inflammation in mice modeled by SS, and to provide a basis for clinical research. MATERIALS AND METHODS: The SS model was set up by submandibular gland (SMG) immune induction method and then treated with TGP for 24 weeks. The fecal characteristics were observed and the fecal number and moisture content were measured. Colonic pathology was observed by H&E staining. The levels of serum P substance (SP), vasoactive intestinal peptide (VIP), interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, nitric oxide (NO), and nitric oxide synthase (NOS) were determined by enzyme linked immunosorbent assay (ELISA) and microplate method, respectively. Reverse transcription polymerase chain reaction (RT-PCR) was employed to analyze the mRNA expression of c-kit and stem cell factor (SCF) in colon. RESULTS: Compared with the model group, the dry and rough condition of the feces was improved, and the fecal gloss, number and moisture content significantly increased after the administration of TGP capsules. Meanwhile, TGP treatment improved colonic pathological damage, inhibited the serum concentrations of NO, NOS, IL-1ß, TNF-α, NF-κB and SP, increased serum VIP concentration, and up-regulated mRNA expression of SCF and c-kit in colon. CONCLUSIONS: TGP could obviously attenuate SS-mediated constipation and intestinal inflammation in mice by acting on some intestinal motility related factors and inflammatory factors.

Zero-fluoroscopy transseptal puncture guided by right atrial electroanatomical mapping combined with intracardiac echocardiography: A single-center experience.

BACKGROUND: Right atrial electroanatomical mapping may be combined with SoundStar 3D diagnostic ultrasound catheter (EAM-ICE) as a zero-fluoroscopy procedure for radiofrequency catheter ablation (RFCA). We aimed to evaluate the efficiency and safety of zero-fluoroscopy transseptal puncture guided by EAM-ICE and fluoroscopy combined with intracardiac echocardiography (F-ICE) in patients with paroxysmal atrial fibrillation (PAF). HYPOTHESIS: Zero-fluoroscopy transseptal puncture is an effective and safe procedure. METHODS: This study had a prospective design. A total of 57 patients with PAF were enrolled and assigned to two groups. Twenty-seven patients were enrolled in the EAM-ICE group, and 30 patients were enrolled in the F-ICE group. RESULTS: There were no statistically significant differences in baseline patient characteristics between groups. Transseptal puncture was successful in all patients (57/57, 100%). Total procedure time and duration of transseptal puncture were lower in the F-ICE group (199.4 ± 26.0 minutes vs 150.7 ± 22.1 minutes, P = 0.000; 118.4 ± 19.7 vs 70.5 ± 13.5 minutes, P = 0.000). There was no use of fluoroscopy in the EAM-ICE group (0 mGy vs 70.5 ± 13.5 mGy); the duration of fluoroscopy in the EAM-ICE group was negligible (0 minutes vs 5.4 ± 1.9 minutes). No procedural complication occurred in either group. CONCLUSIONS: EAM-ICE guided zero-fluoroscopy transseptal puncture is an effective and safe procedure.

Total glucosides of paeony (TGP) alleviates Sjogren's syndrome through inhibiting inflammatory responses in mice.

BACKGROUND: Sjogren's syndrome (SS) is an inflammatory autoimmune disease whose etiology is complicated. Total glucosides of paeony (TGP) has a variety of pharmacological effects. PURPOSE: To evaluate the therapeutic effects of TGP on SS in mice and anti-inflammatory mechanism. STUDY DESIGN: SS animal model was developed from C57BL/6J mice through immunological induction (SS mice) and NOD/ShiltJNju (NOD) mice. Inflammatory cytokines and other related indicators were measured. METHODS: TGP (720, 360, 180 mg/kg) was intragastrically administered for 6 or 16 weeks for SS mice and NOD mice, respectively. Average food and water intake, average body weight, saliva flow, submandibular gland (SMG) and spleen index, and SMG pathology were measured. ELISA was used to evaluate serum inflammatory cytokines in SS mice and autoantigens in NOD mice. Real-time PCR, Western blot and Luminex liquid suspension chip assay were applied to analyze SMG inflammatory cytokines mRNA and protein expression of NOD mice. RESULTS: Compared with SS mice, TGP treatment improved SMG pathological damage. TGP (720 mg/kg) treatment increased saliva flow, and reduced organ indexes and serum IL-6 and IFN-γ concentration. TGP (360 mg/kg) treatment decreased serum IFN-γ concentration. TGP (180 mg/kg) treatment for 6 weeks decreased average body weight. Compared with NOD mice, TGP treatment increased saliva flow from 9 to 15 weeks, decreased body weight, and alleviated pathological damage of SMG after 2 and 16 weeks. After 2 weeks of administration, TGP treatment inhibited serum concentration of SSB/La, SSA/Ro and α-fodrin, decreased TNF-α, IL-1ß and IFN-γ in SMG, and down-regulated protein expressions of BAFF and IL-17A and mRNA expressions of BAFF, TNF-α, IL-17A, CXCL9 and CXCL13 in SMG. After 8 weeks of administration, TGP treatment decreased the concentration of α-fodrin in serum, TNF-α and IL-6 in SMG, and down-regulated mRNA expressions of IL-17A, TNF-α, CXCL9, CXCL13 and BAFF and protein expressions of IL-17A and BAFF in SMG. After 16 weeks of administration, TGP treatment reduced serum SSA/Ro, SSB/La and α-fodrin concentration, and decreased BAFF protein expression and TNF-α, CXCL9, CXCL13, IL-17A, and BAFF mRNA expressions. CONCLUSION: TGP has a certain therapeutic effect on SS mice and NOD mice through inhibiting inflammatory responses.

Ginkgo diterpene lactones inhibit cerebral ischemia/reperfusion induced inflammatory response in astrocytes via TLR4/NF-κB pathway in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. (Ginkgoaceae) is a traditional Chinese medicine known to treating stroke and other cardio-cerebrovascular diseases for thousands of years in China. Ginkgo diterpene lactones (GDL) attracted much attention because of their neuroprotective properties. AIM OF THE STUDY: To uncover the effects of GDL, which consist of ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), on ischemic stroke, as well as the underlying molecular mechanisms. MATERIALS AND METHODS: We used middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R) models mimicking the process of ischemia/reperfusion in vivo and in vitro, respectively. Anticoagulant effects of GDL were investigated on platelet activating factor (PAF), arachidonic acid (AA) and adenosine diphosphate (ADP)-induced platelet aggregation both in vivo and in vitro. We also evaluated the effects of GDL on lipopolysaccharide (LPS)-induced inflammatory response in primary cultured rats' astrocytes. Infarct size, neurological deficit score, and brain edema were measured at 72 h after MCAO. Immunohistochemistry was utilized to analyze neurons necrosis and astrocytes activation. Expression of pro-inflammatory cytokines, including tumor necrotic factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected using enzyme-linked immunosorbent assay (ELISA) and real time PCR. The levels of toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) were assessed by real time PCR or Western blot. RESULTS: Compared with MCAO/R rats, GDL significantly reduced infarct size and brain edema, improved neurological deficit score. Meanwhile, GDL suppressed platelet aggregation, astrocytes activation, pro-inflammatory cytokines releasing, TLR4 mRNA expression and transfer of NF-κB from cytoplasm to nucleus. Furthermore, GDL alleviated OGD/R injury and LPS-induced inflammatory response in primary astrocytes, characterized by promoting cell viability, decreasing lactate dehydrogenase (LDH) activity, and inhibiting IL-1ß and TNF-α releasing. CONCLUSIONS: In summary, GDL attenuate cerebral ischemic injury, inhibit platelet aggregation and astrocytes activation. The anti-inflammatory activity might be associated with the downregulation of TLR4/NF-κB signal pathway. Our present findings provide an innovative insight into the novel treatment of GDL in ischemic stroke therapy.

[Research and development thought on biopharmaceutics classification system of Chinese materia medica].

The biopharmaceutics classification system( BCS) is a scientific framework or method for classifying drugs based on drug solubility and permeability,which can be used to provide drug bioavailability-absorption correlation analysis. Based on the characteristics of multi-component and multi-target of traditional Chinese medicine( TCM) as well as the concept,method and technology of BCS,the research group proposed biopharmaceutics classification system of Chinese materia medica( CMMBCS) and carried out research and data accumulation of classical prescriptions. Based on the previous research results,further development ideas under the CMMBCS concept and framework were further proposed in this study. In the course of research,the influence of the intermediate links of the complex interactions of the multi-component environment was omitted,and the component absorption studies on the main clinical effects of prescription ingredients were directly concerned,or the components and data were reversely extracted from the aspects of metabolism,pharmacodynamic pathways and absorption principles. Studies were conducted from two aspects( single component and compound prescription) to comprehensively evaluate the absorption properties of TCM compound. In the research path,the different ways in which Chinese medicine could exert its efficacy were fully considered,and CMMBCS classification and establishment rules were clarified mainly by focusing on the absorption pathway into the blood. Specifically,the network pharmacology and molecular docking technology were used to screen the compound index components of TCM; the absorption rules were studied by the physiologically based pharmacokinetic models and the absorption parameters of CMMBCS were calculated by reverse reasoning. Then the CMMBCS classification of TCM prescription was corrected by studying the efficacy or absorption pathway. In this paper,the theoretical framework and research methodology of CMMBCS were systematically improved based on the establishment of CMMBCS basic theory,the supplementary of drug-oriented research ideas and the application of modern mature Chinese medicine methodology.