The Emotion Regulation of Acupuncture in Chronic Low Back Pain: A Clinical Neuroimaging Protocol.

Introduction: Acupuncture is effective for patients with chronic low back pain (CLBP), which can relieve pain intensity and regulate negative emotional states such as pain-related anxiety and depression. Previous studies mainly discuss the analgesic mechanism of acupuncture treatment of CLBP, but there are multiple dimensions to pain, including sensation, emotion and cognition. Therefore, this study aims to investigate the central mechanism of acupuncture for CLBP from the perspective of emotional regulation by functional magnetic resonance imaging (fMRI). Methods and Analysis: A total of 72 patients with CLBP will be recruited in the study and randomly assigned to the verum acupuncture group or the sham acupuncture group. The trail will last for 18 weeks including a 2-week baseline, a 4-week treatment and a 12-week for follow-up period. The primary outcomes are the visual analog scale (VAS) and the Japanese Orthopaedic Association Scores (JOA) score. The secondary outcomes are the 12-item short form health survey (SF-12), the state trait anxiety inventory (STAI), the self-rating anxiety scale (SAS) and self-rating depression scale (SDS). The VAS, JOA, STAI SAS and SDS will be collected at baseline, week 2, week 4, and after follow-up. The SF-12 will be evaluated at baseline, week 2 and week 4. Functional magnetic resonance imaging (MRI) data will be collected at baseline and the end of treatment. Emotion-related brain regions will be chosen as regions of interest (ROIs). The gray matter volume (GMV), amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), functional connectivity (FC), and large-scale functional brain network based on these ROIs will be analyzed within and between the two groups. Discussion: This study will verify the emotional regulation of acupuncture and explore the mechanism of acupuncture for emotion regulation in patients with CLBP. Trial Registration Number: https://www.chictr.org.cn/showproj.html?proj=195486, identifier: ChiCTR2300070557.

Diverse terpenoid glycosides with in vitro cytotoxicity from Glechoma longituba.

Terpenoids are the largest class of all known natural products, possessing structural diversity and numerous biological activities. Ten previously undescribed terpenoid glycosides, glechlongsides A-J (1-10), were isolated from the ethanol extract of the whole plant of Glechoma longituba, including diterpenoid glycoside and pentacyclic triterpenoid saponin. The structures of these compounds were characterized by extensive analysis of 1D and 2D NMR as well as HRESIMS spectra. In addition, glechlongsides F-I (6-9) exhibited weak cytotoxicity against human cancer cell lines BGC-823, Be1, HCT-8, A2780, and A549 with IC50 values ranging from 3.77 to 30.95 µM, respectively.

Multiomics Analysis Reveals the Chemical and Genetic Bases of Pigmented Potato Tuber.

Anthocyanins and carotenoids determine the diversity of potato tuber flesh pigmentation; here, the underlying chemical and genetic bases were elucidated by multiomics analyses. A total of 31 anthocyanins and 30 carotenoids were quantified in five differently pigmented tubers. Cyanidin and pelargonidin derivatives determined the redness, while malvidin, petunidin, and delphinidin derivatives contributed to purpleness. Violaxanthin derivatives determined the light-yellow color, while zeaxanthin and antheraxanthin derivatives further enhanced the deep-yellow deposition. Integrated transcriptome and proteome analyses identified that F3'5'H highly enhanced anthocyanin biosynthesis in purple flesh and was responsible for metabolic divergence between red and purple samples. BCH2 significantly enhanced carotenoid biosynthesis in yellow samples and along with ZEP, NCED1, and CCD1 genes determined metabolic divergence between light and deep-yellow samples. The weighted correlation network analysis constructed a regulatory network revealing the central role of AN1 in regulating anthocyanin biosynthesis, and 10 new transcription factors related to anthocyanin and carotenoid metabolism regulation were identified. Our findings provide targeted genes controlling tuber pigmentation, which will be meaningful for the genetic manipulation of tuber quality improvement.

[Construction of jingjin differentiation system based on holistic concept].

As a diagnostic method to guide the treatment of sinew/fascia diseases, jingjin (muscle regions of meridians) differentiation is an important component of syndrome differentiation system of acupuncture and moxibustion. In clinical practice, because of the limitations of the ideological guidance of the holistic view, the systemic and dialectical thinking and the syndrome element collection, the system of diagnosis and treatment of sinew/fascia diseases is not comprehensive. Through combing the origin of the holistic view of jingjin, the paper expounds the differentiation framework of sinew/fascia diseases from 4 aspects of differentiation, i.e. the location of disease, etiology, nature of disease and condition of disease. It suggests to construct jingjin differentiation system by taking the holistic ideas as the core, the syndrome element research as the common method and the evidence-based medicine as the theoretical basis so that the thinking of syndrome differentiation and the diagnostic approaches based on jingjin theory can be enriched.

Electroacupuncture treatment ameliorates metabolic disorders in obese ZDF rats by regulating liver energy metabolism and gut microbiota.

Metabolic disorders represent a major therapeutic challenge to public health worldwide due to their dramatically increasing prevalence. Acupuncture is widely used as adjuvant therapy for multiple metabolic diseases. However, detailed biological interpretation of the acupuncture stimulations is still limited. The gut and the liver are intrinsically connected and related to metabolic function. Microbial metabolites might affect the gut-liver axis through multiple mechanisms. Liver metabolomics and 16S rRNA sequencing were used to explore the specific mechanism of electroacupuncture in treating ZDF rats in this study. Electroacupuncture effectively improved glycolipid metabolism disorders of the ZDF rats. Histopathology confirmed that electroacupuncture improved diffuse hepatic steatosis and hepatocyte vacuolation, and promoted glycogen accumulation in the liver. The treatment significantly improved microbial diversity and richness and upregulated beneficial bacteria that maintain intestinal epithelial homeostasis and decreased bacteria with detrimental metabolic features on host metabolism. Liver metabolomics showed that the main effects of electroacupuncture include reducing the carbon flow and intermediate products in the TCA cycle, regulating the metabolism of various amino acids, and inhibiting hepatic glucose output and de novo lipogenesis. The gut-liver axis correlation analysis showed a strong correlation between the liver metabolites and the gut microbiota, especially allantoin and Adlercreutzia. Electroacupuncture treatment can improve abnormal energy metabolism by reducing oxidative stress, ectopic fat deposition, and altering metabolic fluxes. Our results will help us to further understand the specific mechanism of electroacupuncture in the treatment of metabolic diseases.

Effectiveness of mindfulness-based interventions on mental, cognitive outcomes and neuroplastic changes in older adults with mild cognitive impairment: A systematic review and meta-analysis.

AIMS: To evaluate the effectiveness of mindfulness-based interventions (MBIs) on mental and cognitive outcomes including, anxiety, depression, attention, memory, global cognition and neuroplastic changes in older adults with mild cognitive impairment (MCI). DESIGN: Systematic review and meta-analysis. DATA SOURCE: A three-step search strategy was conducted on eight electronic databases, grey literature and reference lists from inception to February 2022. REVIEW METHODS: Randomized controlled trials (RCTs) examining MBIs on older adults with MCI were screened and assessed for risk of bias using the Cochrane Risk of Bias Tool. Meta-analysis was conducted using RevMan using a random-effect model. Narrative synthesis was performed for studies where results could not be pooled statistically. RESULTS: Ten RCTs were included in the review. Results suggested that right frontal parietal and left inferior temporal gyrus of the brain showed increased cortical thickness after receiving MBIs. There were significant interaction effects for global efficiency and significant interactions in the insular and gyrus regions. Functional connectivity between the posterior cingulate cortex, bilateral medial prefrontal cortex and left hippocampus were increased in participants undergoing MBIs. Nevertheless, meta-analysis showed non-significant pooled effects, favouring control groups on anxiety, depression, attention, memory and global cognition. CONCLUSION: This review suggested the potential effects of MBIs in improving cortical thickness and connectivity in regions associated with memory and attention. Nevertheless, the effects of MBIs compared to active control groups on depression, anxiety, attention, memory and global cognition are inconclusive due to the lack of studies and non-significant results. IMPACT: The review advocates for more rigorous studies with larger sample size and utilizing wait-list controls to evaluate the effects of MBIs. MBIs can be considered as an adjunct with other therapies to further enhance the effect on psychological and cognitive outcomes for older adults with MCI. No Patient or Public Contribution as this is a meta-analysis.

Prediction and verification of the active ingredients and potential targets of Erhuang Quzhi Granules on non-alcoholic fatty liver disease based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Erhuang Quzhi Granules (EQG) is a compound composed of 13 traditional Chinese medicines developed by the First Affiliated Hospital of Shihezi University. In clinical practice, EQG has been applied to the treatment of hyperlipidemia and non-alcoholic fatty liver disease (NAFLD), and could significantly improve the serum biochemical indicators of NAFLD patients. AIM OF THE STUDY: This study aims to explore the bioactive compounds, potential targets, and molecular mechanisms of EQG against NAFLD through network pharmacology, molecular docking, and experimental verification. MATERIALS AND METHODS: The chemical components of EQG came from the literature and quality standard. Bioactive compounds were screened based on the absorption, distribution, metabolism, and excretion (ADME) feature, and their potential targets were predicted using the substructure-drug-target network-based inference (SDTNBI). The core targets and signaling pathways were obtained through the analysis of protein-protein interaction (PPI), gene ontology (GO) function, and Kyoto encyclopedia of genes and genomes (KEGG) pathway. The results were further confirmed by literature retrieval, molecular docking, and in vivo experiments. RESULTS: The results of network pharmacology showed 12 active ingredients and 10 core targets for EQG in treating NAFLD. And EQG mainly regulates lipid and atherosclerosis-related pathways to improve NAFLD. The collected literature verified the regulatory effect of the active components of EQG on core targets TP53, PPARG, EGFR, HIF1A, PPARA, and MTOR. Molecular docking results showed that Aloe-Emodin (AE), Emodin, Physcion, and Rhein (RH) had stable binding structures with the core targets HSP90AA1. In vivo experiment showed that AE and RH reduced aspartate transaminase (AST), alanine aminotransferase (ALT), interleukin (IL)-1ß, IL-6, IL18, and tumor necrosis factor α (TNF-α) in the serum or liver of NAFLD mice, improved liver lipid deposition and fibrosis, and inhibit gene expression of nuclear factor kappa B (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), IL-1ß, TNF-α and protein expression of HSP90, NF-κB and Cleaved caspase-1. CONCLUSIONS: This study comprehensively revealed the biological compounds, potential targets, and molecular mechanisms of EQG in the treatment of NAFLD, providing a reference basis for the promotion of EQG in the clinic.

[Mechanism of Didang Decoction in prevention of anti-atherosclerosis and hyperlipidemia by HPLC-Q-TOF-MS/MS and network pharmacology based on theory of "nutrients return to heart and fat accumulates in channels"].

Atherosclerosis(AS) is caused by impaired lipid metabolism, which deposits lipids in the intima, causes vascular fibrosis and calcification, and then leads to stiffening of the vascular wall. Hyperlipidemia(HLP) is one of the key risk factors for AS. Based on the theory of "nutrients return to the heart and fat accumulates in the channels", it is believed that the excess fat returning to the heart in the vessels is the key pathogenic factor of AS. The accumulation of fat in the vessels over time and the blood stasis are the pathological mechanisms leading to the development of HLP and AS, and "turbid phlegm and fat" and "blood stasis" are the pathological products of the progression of HLP into AS. Didang Decoction(DDD) is a potent prescription effective in activating blood circulation, removing blood stasis, resolving turbidity, lowering lipids, and dredging blood vessels, with the functions of dispelling stasis to promote regeneration, which has certain effects in the treatment of atherosclerotic diseases. This study employed high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS) to screen the main blood components of DDD, explored the targets and mechanisms of DDD against AS and HLP with network pharmacology, and verified the network pharmacological results by in vitro experiments. A total of 231 blood components of DDD were obtained, including 157 compounds with a composite score >60. There were 903 predicted targets obtained from SwissTargetPrediction and 279 disease targets from GeneCards, OMIM, and DisGeNET, and 79 potential target genes of DDD against AS and HLP were obtained by intersection. Gene Ontology(GO) analysis suggested that DDD presumably exerted regulation through biological processes such as cholesterol metabolism and inflammatory response, and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis suggested that signaling pathways included lipid and atherosclerosis, insulin resistance, chemo-carcinogenesis-receptor activation, and AGE-RAGE signaling pathways in diabetic complications. In vitro experiments showed that DDD could reduce free fatty acid-induced lipid accumulation and cholesterol ester content in L02 cells and improve cellular activity, which might be related to the up-regulation of the expression of PPARα, LPL, PPARG, VEGFA, CETP, CYP1A1, and CYP3A4, and the down-regulation of the expression of TNF-α and IL-6. DDD may play a role in preventing and treating AS and HLP by improving lipid metabolism and inflammatory response, and inhibiting apoptosis with multi-component, multi-target, and multi-pathway characteristics.

[Pathogenesis and staging treatment for non-specific low back pain based on the meridian sinew theory].

Based on the physiological and pathological characteristics of meridian sinew theory, the staging treatment of non-specific low back pain (NLBP) is explored to provide the reference of clinical practice. The twelve meridian sinews of the human body communicate with the bones and joints of the whole body, which governs the movement, body protection and defense, and meridian regulation. Physiologically, the meridian sinew maintains the functions of the lumbar region. In pathology, the meridian sinew may encounter stasis and pain, contraction and spasm or "transverse collateral" formation. According to the pathological staging of meridian sinew disorders, the progress of NLBP is divided into 3 phases and the corresponding treatments are provided. Mild stimulation and rapid analgesia is suggested to promote tissue repair at the early phase; muscle spasm is relieved to adjust muscular status at the middle phase; and the "cord-like" muscle foci is removed at the later phase of the disease.

Bioactive Phytochemicals and Molecular Mechanisms of Artemisiae capillariae against Drug Induced Liver Injury based on Network Pharmacology.

BACKGROUND: Artemisiae capillariae (Yinchen, YC) is a well-known herbal medicine used to treat drug-induced liver diseases, while the bioactive phytochemicals and pharmacological targets of YC remain unclear. OBJECTIVE: The study aimed to probe the key active components in YC and determine the potential molecular mechanisms of YC protect against DILI. METHODS: In this study, we first delved into the active chemicals and targets of YC, identified potential anti-AILI targets for YC, mapped the components-targets network, performed proteinprotein interaction (PPI) analysis, gene ontology (GO) enrichment, and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analyses of the action targets. This led to figure out the liver protective mechanism of YC against AILI. Analyzing the molecular docking of key targets, binding domain of ingredients and targets reveals the effective interaction, and the binding energy explains the efficiency and stability of the interactions. RESULTS: Network analysis identified 53 components in YC; by systematic screening 13 compounds were selected, which were associated with 123 AILI-related genes. The core ingredients were quercetin, capillarisin and Skrofulein, and the identified crucial genes were AKT1, TNF, and IL6. The GO and KEGG pathway enrichment analysis results indicated that the anti-AILI targets of YC mainly take a part in the regulation of oxidative stress and immune, with related signaling pathways including PI3K/AKT and IL17. Furthermore, the binding pockets of YC bioactive ingredients and key targets were revealed, and the binding ability was proved by molecular docking analysis. CONCLUSION: This study has revealed the potential bioactive molecules and mechanism of YC in AILI and provided a possible strategy for the identification of active phytochemicals against druginduced liver injury.

New furofuran and tetrahydrofuran lignans from the flower buds of Magnolia biondii Pamp and their antiallergic effects.

The dried flower buds of Magnolia biondii Pamp (herbal name, Xin-Yi) are a traditional Chinese medicine with a long history of clinical use in the treatment of allergic rhinitis and sinusitis. However, the constituents responsible for its antiallergic effects remain clearly unidentified. In the present study, totally 33 lignans were obtained from M. biondii. Among them, two novel furofuran lignans (1 and 2), two novel tetrahydrofuran lignans (3 and 4), and other 16 known lignans were isolated first time from M. biondii. The antiallergic effects of compounds 1-33 on mouse bone marrow-derived mast cells (BMMCs) degrunaliton were evaluated and results showed that compounds 7, 8, 13, 15 and 18 could significantly inhibited ß-hex release on BMMCs. The results proved that furofuran and tetrahydrofuran lignans were the main constituents in M. biondii and their antiallergic effects were related with suppressing mast cell activation.

Effects of anthocyanin-rich supplementation on cognition of the cognitively healthy middle-aged and older adults: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: The prevalence of age-related cognitive decline has been on the rise as the global population age, putting the independence and quality of life of elderly at risk. Anthocyanin, as a subclass of dietary flavonoids, may have a beneficial impact on cognitive outcomes. OBJECTIVES: To examine the effects of dietary anthocyanin supplementation on cognition of the cognitively healthy middle-aged and older adults. DATA SOURCES: PubMed, ScienceDirect, CINAHL, EMBASE, ProQuest and Cochrane databases were searched. DATA EXTRACTION AND ANALYSIS: Thirteen studies were included in this meta-analysis. Anthocyanin-rich supplementation was found to significantly improve the processing speed of the older adults (95%CI 0.08, 0.44; P = 0.004). No significant differences were observed between intervention and control groups on memory, attention, executive function and psychomotor performance. Current neuroimaging studies have found promising effects of anthocyanin supplementation on brain activation and cerebral perfusion. CONCLUSION: Anthocyanin-rich supplementation may preserve cognitive processing speed and neuro-activities in older adults, which improves their daily functioning and quality of life. This review provides useful insights to guide direction and methodological designs for future studies to explore the underlying mechanisms of anthocyanins. SYSTEMATIC REVIEW AND META-ANALYSIS REGISTRATION: PROSPERO registration No. CRD42021228007.

Prevention of polycystic ovary syndrome and postmenopausal osteoporosis by inhibiting apoptosis with Shenling Baizhu powder compound.

Objective: Shenling Baizhu powder (SBP) has been shown to reverse the abnormal expression of the aromatic hydrocarbon receptor (AHR) mediated by air pollution. Our study aimed to understand the main ingredient of SBP and investigate its action mechanism in preventing polycystic ovary syndrome (POCS) and postmenopausal osteoporosis (PMO). Methods: The active ingredients of SBP with the highest binding affinity to AHR were screened using a Chinese medicine database, and their binding mechanism was simulated using molecular dynamics simulation (MDS). Rutin was utilized to treat ovarian granulosa cell lines and osteoblast cell lines. The cell lines were treated with a gradient of rutin concentration (0.01 mmol/L, 0.05 mmol/L and 0.1 mmol/L) to find the optimal drug dose. PCR was used to detect AHR and apoptosis-related proteins, and WB to detect the expression of AHR, caspase-3 and cleaved-caspase-3. Finally, the CCK-8 cell proliferation assay detected the proliferation of cells. Results: We obtained Rutin through the Chinese medicine database, and dynamics simulation determined its binding sites. Ovarian granulosa cell lines and osteoblast cell lines were treated with Rutin. RT-PCR and western blotting revealed that the expression of apoptosis-associated protein Bcl-2 was elevated, and the expression of AHR, Bax, caspase-3 and PARP were decreased. CCK-8 results showed accelerated proliferation in both cell types. Conclusion: Rutin, the main ingredient of SBP compound, works by binding to AHR, which can improve POCS and PMO by inhibiting cell apoptosis and by promoting cell proliferation.

Combination of phototherapy with immune checkpoint blockade: Theory and practice in cancer.

Immune checkpoint blockade (ICB) therapy has evolved as a revolutionized therapeutic modality to eradicate tumor cells by releasing the brake of the antitumor immune response. However, only a subset of patients could benefit from ICB treatment currently. Phototherapy usually includes photothermal therapy (PTT) and photodynamic therapy (PDT). PTT exerts a local therapeutic effect by using photothermal agents to generate heat upon laser irradiation. PDT utilizes irradiated photosensitizers with a laser to produce reactive oxygen species to kill the target cells. Both PTT and PDT can induce immunogenic cell death in tumors to activate antigen-presenting cells and promote T cell infiltration. Therefore, combining ICB treatment with PTT/PDT can enhance the antitumor immune response and prevent tumor metastases and recurrence. In this review, we summarized the mechanism of phototherapy in cancer immunotherapy and discussed the recent advances in the development of phototherapy combined with ICB therapy to treat malignant tumors. Moreover, we also outlined the significant progress of phototherapy combined with targeted therapy or chemotherapy to improve ICB in preclinical and clinical studies. Finally, we analyzed the current challenges of this novel combination treatment regimen. We believe that the next-generation technology breakthrough in cancer treatment may come from this combinational win-win strategy of photoimmunotherapy.

[Metabolic engineering study on biosynthesis of 4-hydroxybenzyl alcohol from L-tyrosine in Escherichia coli].

As an important active ingredient in the rare Chinese herb Gastrodiae Rhizoma and also the main precursor for gastrodin biosynthesis, 4-hydroxybenzyl alcohol has multiple pharmacological activities such as anti-inflammation, anti-tumor, and anti-cerebral ischemia. The pharmaceutical products with 4-hydroxybenzyl alcohol as the main component have been increasingly favored. At present, 4-hydroxybenzyl alcohol is mainly obtained by natural extraction and chemical synthesis, both of which, however, exhibit some shortcomings that limit the long-term application of 4-hydroxybenzyl alcohol. The wild and cultivated Gastrodia elata resources are limited. The chemical synthesis requires many steps, long time, and harsh reaction conditions. Besides, the resulting by-products are massive and three reaction wastes are difficult to treat. Therefore, how to artificially prepare 4-hydroxybenzyl alcohol with high yield and purity has become an urgent problem facing the medical researchers. Guided by the theory of microbial metabolic engineering, this study employed the genetic engineering technologies to introduce three genes ThiH, pchF and pchC into Escherichia coli for synthesizing 4-hydroxybenzyl alcohol with L-tyrosine. And the fermentation conditions of engineering strain for producing 4-hydroxybenzyl alcohol in shake flask were also discussed. The experimental results showed that under the conditions of 0.5 mmol·L~(-1) IPTG, 15 ℃ induction temperature, and 40 ℃ transformation temperature, M9 Y medium containing 200 mg·L~(-1) L-tyrosine could be transformed into(69±5)mg·L~(-1) 4-hydroxybenzyl alcohol, which has laid a foundation for producing 4-hydroxybenzyl alcohol economically and efficiently by further expanding the fermentation scale in the future.

Lactobacillus paracasei L9 improves colitis by expanding butyrate-producing bacteria that inhibit the IL-6/STAT3 signaling pathway.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammation that is currently incurable. Increasing evidence indicates that supplementation with probiotics could improve the symptoms of IBD. It is scientifically significant to identify novel and valid strains for treating IBD. It has been reported that the probiotic Lactobacillus paracasei L9 (L9), which is identified from the gut of healthy centenarians, can modulate host immunity and plays an anti-allergic role. Here, we demonstrated that L9 alleviates the pathological phenotypes of experimental colitis by expanding the abundance of butyrate-producing bacteria. Oral administration of sodium butyrate in experimental colitis recapitulates the L9 anti-inflammatory phenotypes. Mechanistically, sodium butyrate ameliorated the inflammatory responses by inhibiting the IL-6/STAT3 signaling pathway in colitis. Overall, these findings demonstrated that L9 alleviates the DSS-induced colitis development by enhancing the abundance of butyrate-producing bacterial strains that produce butyrate to suppress the IL-6/STAT3 signaling pathway, providing new insight into a promising therapeutic target for the remission of IBD.

Shoulder transcutaneous electric nerve stimulation decreases heart rate via potentiating vagal tone.

By enhancing vagal activity, auricle transcutaneous electric nerve stimulation (TENS) is developed as a non-invasive therapy for heart failure. Nevertheless, though shoulder TENS used for treating adhesive capsulitis could affect vagal tone, its potential impact on heart functions remains unclear. In this study, electrocardiogram (ECG) and heart rate (HR) of subjects in response to sham, right-sided, or left-sided shoulder TENS (TENS-S, TENS-R, and TENS-L, respectively; 5 min) were recorded and analyzed. During the stimulation period, TENS-R constantly and TENS-L transiently decreased the HR of subjects; both TENS-R and TENS-L increased powers of the low- and high-frequency spectra. While TENS-R exhibiting no effect, TENS-L increased the ratio of low/high-frequency power spectrum indicating TENS-R decreased the HR through potentiating cardiac vagal tone. Collectively, these results suggest TENS could be an early and non-invasive therapy for heart failure patients before considering implant devices or devices are not feasible; moreover, therapists/physicians need to carefully monitor the potential adverse events during treatment for patient safety.Trial registration: The study protocol was registered in ClinicalTrials.gov (NCT03982472; 11/06/2019).

Clinical competence and its association with self-efficacy and clinical learning environments among Chinese undergraduate nursing students.

Evaluation and cultivation of clinical competence in undergraduate nursing students are essential in nursing education. Self-efficacy and good clinical learning environments are expected to have a positive influence on the clinical competence of undergraduate nursing students, but few studies have focused on the relationships among clinical competence, self-efficacy, and clinical learning environments. This study aimed to examine clinical competence and its association with self-efficacy and clinical learning environments among Chinese undergraduate nursing students. A cross-sectional questionnaire survey was conducted with 1518 undergraduate nursing students being recruited from five medical colleges in China. The nursing students' clinical competence, self-efficacy, and clinical learning environments were assessed using a set of self-reported questionnaires, including Chinese versions of the Holistic Clinical Assessment Tool; General Self-Efficacy Scale; and Clinical Learning Environment, Supervision, and Nurse Teacher Evaluation Scale. Factors significantly associated with the clinical competence of undergraduate nursing students were professional interest, self-efficacy, and clinical learning environments, accounting for 36.1% of the total variance. Self-efficacy played a mediating role between clinical learning environments and clinical competence. The results of this study can be applied as reference for the enhancement of a nursing education program to improve the clinical competence of Chinese undergraduate nursing students.

Highly Oxygenated Triterpenoids and Diterpenoids from Fructus Rubi (Rubus chingii Hu) and Their NF-kappa B Inhibitory Effects.

During a phytochemical investigation of the unripe fruits of Rubus chingii Hu (i.e., Fructus Rubi, a traditional Chinese medicine named "Fu-Pen-Zi"), a number of highly oxygenated terpenoids were isolated and characterized. These included nine ursane-type (1, 2, and 4-10), five oleanane-type (3, 11-14), and six cucurbitane-type (15-20) triterpenoids, together with five ent-kaurane-type diterpenoids (21-25). Among them, (4R,5R,8R,9R,10R,14S,17S,18S,19R,20R)-2,19α,23-trihydroxy-3-oxo-urs-1,12-dien-28-oic acid (rubusacid A, 1), (2R*,4S*,5R*,8R*,9R*,10R*,14S*,17S*, 18S*,19R*,20R*)-2α,19α,24-trihydroxy-3-oxo-urs-12-en-28-oic acid (rubusacid B, 2), (5R,8R,9R,10R, 14S,17R,18S,19S)-2,19α-dihydroxy-olean-1,12-dien-28-oic acid (rubusacid C, 3), and (3S,5S,8S,9R, 10S,13R,16R)-3α,16α,17-trihydroxy-ent-kaur-2-one (rubusone, 21) were previously undescribed. Their chemical structures and absolute configurations were elucidated on the basis of spectroscopic data and electronic circular dichroism (ECD) analyses. Compounds 1 and 3 are rare naturally occurring pentacyclic triterpenoids featuring a special α,ß-unsaturated keto-enol (diosphenol) unit in ring A. Cucurbitacin B (15), cucurbitacin D (16), and 3α,16α,20(R),25-tetrahydroxy-cucurbita-5,23- dien-2,11,22-trione (17) were found to have remarkable inhibitory effects against NF-κB, with IC50 values of 0.08, 0.61, and 1.60 µM, respectively.