Optimized therapeutic potential of Yinchenhao decoction for cholestatic hepatitis by combined network meta-analysis and network pharmacology.

BACKGROUND: Cholestatic hepatitis is recognized as a significant contributor to the development of liver fibrosis and cirrhosis. As a well-known classic formula for the treatment of cholestatic hepatitis, Yinchenhao decoction (YCHD) is widely used in countries in Asia, including China, Japan, and Korea. However, in recent years, a risk of liver injury has been reported from Rheum palmatum L. and Gardenia jasmonoides J.Ellis which are the main ingredients of YCHD. Therefore, the question arises whether YCHD is still safe enough for the treatment of cholestatic hepatitis or whether an optimized ratio of ingredients should be applied. These is inevitable questions for the clinical application of YCHD. PURPOSE: To provide a scientific basis for the clinical application of YCHD through a combination of meta-analysis and network pharmacology and to find the best ratio of components to ensure optimal therapeutic efficacy and safety. At the same time, a deeper understanding of the mechanisms of YCHD was explored. METHODS: We retrieved relevant trials from various databases including PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases up to August 2023. After screening for inclusion and exclusion criteria, we assessed efficiency, ALT, AST, and TBIL as outcome parameters. The relevant data underwent a network meta-analysis using STATA 16.0 software. Based on network pharmacology, we screened the disease targets, active ingredients, and targets related to YCHD. The targets were visualized using Cytoscape 3.9.1. Then, potential mechanisms were explored based on bioinformatic techniques. RESULTS: Twenty eligible studies were finally screened and a total of 1,591 patients who fulfilled the inclusion criteria were enrolled in the study. The meta-analysis results indicated that TG-c (treatment group c) [(Artemisia capillaris Thunb. : Gardenia jasminoides J.Ellis : Rheum palmatum L. = 10:5:2-10:5:3) + CT] was the most promising therapeutic approach, demonstrating superior efficacy and notable improvements in both AST and TBIL levels. For ALT, TG-d [(Artemisia capillaris : Gardenia jasminoides : Rheum palmatum = 5:1:1-5:2:1) + CT] exhibited the greatest potential as optimal therapy option. Based on the surface under the cumulative ranking curve (SUCRA) values, TG-c was the best therapy in terms of efficiency and improvement in TBIL levels, while TG-d was the most effective in reducing ALT levels. For AST levels, TG-e [(Artemisia capillaris : Gardenia jasminoides : Rheum palmatum = 5:2:2-5:3:3) + CT] was the most effective therapy. The comprehensive analysis revealed that TG-c exhibited the most pronounced efficacy. Combined network pharmacology, GO enrichment analysis and KEGG pathway enrichment analysis displayed that the key target genes of Artemisia capillaris, Rheum palmatum, and Gardenia jasminoides were closely involved in inflammation response, bile transport, apoptosis, oxidative stress, and regulation of leukocyte migration. Notably, bile secretion dominated the common pathway of the three herbs. On the other hand, Artemisia capillaris exhibited a unique mode of action by regulating the IL-17 signaling pathway, which may play a crucial role in its effectiveness. CONCLUSION: Based on our findings, the optimal TG-C demonstrated the most favorable overall therapeutic efficacy by increasing the dosage of Artemisia capillaris while reducing the dosage of Gardenia jasminoides and Rheum palmatum. This is attributed to the potent ability of Artemisia capillaris. to effectively modulate the IL-17 signaling pathway, thereby exerting a beneficial therapeutic effect. Conversely, Gardenia jasminoides and Rheum palmatum may potentially enhance the activation of the NF-кB signaling pathway, thereby elevating the risk of hepatotoxicity.

Icariin mitigates anxiety-like behaviors induced by hemorrhagic shock and resuscitation via inhibiting of astrocytic activation.

BACKGROUND: Abnormal activation of astrocytes in the amygdala contributes to anxiety after hemorrhagic shock and resuscitation (HSR). Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)-associated epigenetic reprogramming of astrocytic activation is crucial to anxiety. A bioactive monomer derived from Epimedium icariin (ICA) has been reported to modulate NF-κB signaling and astrocytic activation. PURPOSE: The present study aimed to investigate the effects of ICA on post-HSR anxiety disorders and its potential mechanism of action. METHODS: We first induced HSR in mice through a bleeding and re-transfusion model and selectively inhibited and activated astrocytes in the amygdala using chemogenetics. Then, ICA (40 mg/kg) was administered by oral gavage once daily for 21 days. Behavioral, electrophysiological, and pathological changes were assessed after HSR using the light-dark transition test, elevated plus maze, recording of local field potential (LFP), and immunofluorescence assays. RESULTS: Exposure to HSR reduced the duration of the light chamber and attenuated open-arm entries. Moreover, HSR exposure increased the theta oscillation power in the amygdala and upregulated NF-κB p65, H3K27ac, and H3K4me3 expression. Contrarily, chemogenetic inhibition of astrocytes significantly reversed these changes. Chemogenetic inhibition in astrocytes was simulated by ICA, but chemogenetic activation of astrocytes blocked the neuroprotective effects of ICA. CONCLUSION: ICA mitigated anxiety-like behaviors induced by HSR in mice via inhibiting astrocytic activation, which is possibly associated with NF-κB-induced epigenetic reprogramming.

Inter-brain neural mechanism and influencing factors underlying different cooperative behaviors: a hyperscanning study.

Cooperative behavior is a vital social interaction which plays a vital role in improving human survival and reproduction. However, few empirical studies have examined the differences between cooperative behaviors and the underlying neural substrates. In the present study, the brain activity of familiar dyads of the same sex was measured using functional near-infrared spectroscopy during three cooperative tasks (cooperative button-press, tangram, and Jenga tasks). We also measured the dyads' empathic abilities and personality traits to investigate the relationships between individual characteristics and neural markers. The results showed that first, there were significant differences in intra-brain activation and inter-brain synchronization among different cooperative tasks in three dimensions: social cognition, behavioral response, and cognitive processing. Second, male participants require stronger intra-brain activation to achieve the same inter-brain synchronization level as women in cooperative tasks. Third, when performing cooperative tasks involving high cognitive demands, Big Five Neuroticism may be an important predictor of neural activation in female participants. Inter-brain synchronization plays an important role in the frontal and temporoparietal junctions during interpersonal cooperation. Furthermore, this study demonstrates that mutual prediction theory is crucial for understanding the neural mechanisms of cooperative behavior.

Increased interbrain synchronization and neural efficiency of the frontal cortex to enhance human coordinative behavior: A combined hyper-tES and fNIRS study.

Coordination is crucial for individuals to achieve common goals; however, the causal relationship between coordination behavior and neural activity has not yet been explored. Interbrain synchronization (IBS) and neural efficiency in cortical areas associated with the mirror neuron system (MNS) are considered two potential brain mechanisms. In the present study, we attempted to clarify how the two mechanisms facilitate coordination using hypertranscranial electrical stimulation (hyper-tES). A total of 124 healthy young adults were randomly divided into three groups (the hyper-tACS, hyper-tDCS and sham groups) and underwent modulation of the right inferior frontal gyrus (IFG) during functional near-infrared spectroscopy (fNIRS). Increased IBS of the PFC or neural efficiency of the right IFG (related to the MNS) was accompanied by greater coordination behavior; IBS had longer-lasting effects on behavior. Our findings highlight the importance of IBS and neural efficiency of the frontal cortex for coordination and suggest potential interventions to improve coordination in different temporal windows.

Efficacy and Related Factors of Artificial Femoral Head Replacement for Femoral Intertrochanteric Fracture and Nonunion: A Systematic Review and Meta-Analysis.

Background: An intertrochanteric fracture can cause ischemic necrosis in the femoral head, leading to negative effects. There are many types of implants for this fracture procedure, including metal-on-metal, metal-on-polyethylene, ceramic-on-ceramic, and ceramic-on-polyethylene, that are currently in use. The current modification is a hybrid prosthetic implant with high functional capacity compared with predecessors. This study aims to determine the procedure's efficacy in recovery, function restoration, complications, and cost-effectiveness. Methods: Our study used a total of 200 patients undergoing total hip arthroplasty and 135 patients undergoing semi-hip arthroplasty to determine the effectiveness of total hip arthroplasty and femoral head arthroplasty From May 2022 to May 2023. Using the RAOSOFT sampling technique, 132 and 101 in the observation and control group, respectively, the sample is obtained with a confidence interval of 95%, an error margin of 1%, and response interval confidence of 50%. This is a descriptive type of research that relies on a meta-analysis of the available data from PubMed, scholarly articles, and the Chinese biomedical database to gather the fundamental data needed to conduct the research. Data obtained is analyzed using SSPS and STATA and presented in tables showing a summary of the objective measured value. Result: In this study, the Harris joint score of patients in the total hip arthroplasty group was significantly higher than that of the control group, indicating that total hip arthroplasty can restore femoral head function, but still lacks absolute strength like half hip arthroplasty. Conclusions: Femoral head replacement is a complex procedure, but the efficacy in restoring the function is better. In conclusion, despite slow healing and regeneration, the efficacy of complete artificial femoral head replacement is higher in restoring function for various fractures.

Acupuncture at Back-Shu point improves insomnia by reducing inflammation and inhibiting the ERK/NF-κB signaling pathway.

BACKGROUND: Insomnia is a disease where individuals cannot maintain a steady and stable sleep state or fail to fall asleep. Western medicine mainly uses sedatives and hypnotic drugs to treat insomnia, and long-term use is prone to drug resistance and other adverse reactions. Acupuncture has a good curative effect and unique advantages in the treatment of insomnia. AIM: To explore the molecular mechanism of acupuncture at Back-Shu point for the treatment of insomnia. METHODS: We first prepared a rat model of insomnia, and then carried out acupuncture for 7 consecutive days. After treatment, the sleep time and general behavior of the rats were determined. The Morris water maze test was used to assess the learning ability and spatial memory ability of the rats. The expression levels of inflammatory cytokines in serum and the hippocampus were detected by ELISA. qRT-PCR was used to detect the mRNA expression changes in the ERK/NF-κB signaling pathway. Western blot and immunohistochemistry were carried out to evaluate the protein expression levels of RAF-1, MEK-2, ERK1/2 and NF-κB. RESULTS: Acupuncture can prolong sleep duration, and improve mental state, activity, diet volume, learning ability and spatial memory. In addition, acupuncture increased the release of 1L-1ß, 1L-6 and TNF-α in serum and the hippocampus and inhibited the mRNA and protein expression of the ERK/NF-κB signaling pathway. CONCLUSION: These findings suggest that acupuncture at Back-Shu point can inhibit the ERK/NF-κB signaling pathway and treat insomnia by increasing the release of inflammatory cytokines in the hippo-campus.

Therapeutic potential of natural molecules against Alzheimer's disease via SIRT1 modulation.

Alzheimer's disease (AD) is a neurodegenerative disease mainly characterized by progressive cognitive dysfunction and memory impairment. Recent studies have shown that regulating silent information regulator 1 (SIRT1) expression has a significant neuroprotective effect, and SIRT1 may become a new therapeutic target for AD. Natural molecules are an important source of drug development for use in AD therapy and may regulate a wide range of biological events by regulating SIRT1 as well as other SIRT1-mediated signaling pathways. This review aims to summarize the correlation between SIRT1 and AD and to identify in vivo and in vitro studies investigating the anti-AD properties of natural molecules as modulators of SIRT1 and SIRT1-mediated signaling pathways. A literature search was conducted for studies published between January 2000 and October 2022 using various literature databases, including Web of Science, PubMed, Google Scholar, Science Direct, and EMBASE. Natural molecules, such as resveratrol, quercetin, icariin, bisdemethoxycurcumin, dihydromyricetin, salidroside, patchouli, sesamin, rhein, ligustilide, tetramethoxyflavanone, 1-theanine, schisandrin, curcumin, betaine, pterostilbene, ampelopsin, schisanhenol, and eriodictyol, have the potential to modulate SIRT1 and SIRT1 signaling pathways, thereby combating AD. The natural molecules modulating SIRT1 discussed in this review provide a potentially novel multi-mechanistic therapeutic strategy for AD. However, future clinical trials need to be conducted to further investigate their beneficial properties and to determine the safety and efficacy of SIRT1 natural activators against AD.

Vacancy defect-promoted nanomaterials for efficient phototherapy and phototherapy-based multimodal Synergistic Therapy.

Phototherapy and multimodal synergistic phototherapy (including synergistic photothermal and photodynamic therapy as well as combined phototherapy and other therapies) are promising to achieve accurate diagnosis and efficient treatment for tumor, providing a novel opportunity to overcome cancer. Notably, various nanomaterials have made significant contributions to phototherapy through both improving therapeutic efficiency and reducing side effects. The most key factor affecting the performance of phototherapeutic nanomaterials is their microstructure which in principle determines their physicochemical properties and the resulting phototherapeutic efficiency. Vacancy defects ubiquitously existing in phototherapeutic nanomaterials have a great influence on their microstructure, and constructing and regulating vacancy defect in phototherapeutic nanomaterials is an essential and effective strategy for modulating their microstructure and improving their phototherapeutic efficacy. Thus, this inspires growing research interest in vacancy engineering strategies and vacancy-engineered nanomaterials for phototherapy. In this review, we summarize the understanding, construction, and application of vacancy defects in phototherapeutic nanomaterials. Starting from the perspective of defect chemistry and engineering, we also review the types, structural features, and properties of vacancy defects in phototherapeutic nanomaterials. Finally, we focus on the representative vacancy defective nanomaterials recently developed through vacancy engineering for phototherapy, and discuss the significant influence and role of vacancy defects on phototherapy and multimodal synergistic phototherapy. Therefore, we sincerely hope that this review can provide a profound understanding and inspiration for the design of advanced phototherapeutic nanomaterials, and significantly promote the development of the efficient therapies against tumor.

SAR study culminates in a series of HDAC6 selective inhibitors featuring Schisandrin C-analogous Cap as potential immunomodulatory agents for cancer therapy.

HDAC6 inhibitors (HDAC6is) represent an emerging therapeutic option for triggering anti-cancer immune response. In this work, a novel series of HDAC6is, derived from an in-house analog of the traditional Chinese medicine monomer Schisandrin C, were designed and synthesized for SAR study. Throughout the 29 target compounds, 24a, 24b and 24h exerted single-digit nanomolar enzymatic activity and remarkably elevated subtype selectivity compared to the clinically investigated HDAC6i Ricolinostat (Selectivity index = 3.3). In A549 tumor cells, 24h, as the representative in this series (IC50 = 7.7 nM; selectivity index = 31.4), was capable of reversing IL-6-mediated PD-L1 upregulation, highlighting its immunomodulatory capability. Importantly, unlike numerous other hydroxamate-based HDACis, 24h displayed an acceptable oral bioavailability in Sprague-Dawley rats, along with high plasma exposure, long elimination half-life and slow clearance. With the aforementioned attractive performance, 24h deserves further in vivo investigation as an immunomodulatory therapeutic agent for batting human malignance.

A Functional Screening Identifies a New Organic Selenium Compound Targeting Cancer Stem Cells: Role of c-Myc Transcription Activity Inhibition in Liver Cancer.

Cancer stem cells (CSCs) are reported to play essential roles in chemoresistance and metastasis. Pathways regulating CSC self-renewal and proliferation, such as Hedgehog, Notch, Wnt/ß-catenin, TGF-ß, and Myc, may be potential therapeutic targets. Here, a functional screening from the focused library with 365 compounds is performed by a step-by-step strategy. Among these candidate molecules, phenyl-2-pyrimidinyl ketone 4-allyl-3-amino selenourea (CU27) is chosen for further identification because it proves to be the most effective compound over others on CSC inhibition. Through ingenuity pathway analysis, it is shown CU27 may inhibit CSC through a well-known stemness-related transcription factor c-Myc. Gene set enrichment analysis, dual-luciferase reporter assays, expression levels of typical c-Myc targets, molecular docking, surface plasmon resonance, immunoprecipitation, and chromatin immunoprecipitation are conducted. These results together suggest CU27 binds c-Myc bHLH/LZ domains, inhibits c-Myc-Max complex formation, and prevents its occupancy on target gene promoters. In mouse models, CU27 significantly sensitizes sorafenib-resistant tumor to sorafenib, reduces the primary tumor size, and inhibits CSC generation, showing a dramatic anti-metastasis potential. Taken together, CU27 exerts inhibitory effects on CSC and CSC-associated traits in hepatocellular carcinoma (HCC) via c-Myc transcription activity inhibition. CU27 may be a promising therapeutic to treat sorafenib-resistant HCC.

Gallic Acid Alleviates Visceral Pain and Depression via Inhibition of P2X7 Receptor.

Chronic visceral pain can occur in many disorders, the most common of which is irritable bowel syndrome (IBS). Moreover, depression is a frequent comorbidity of chronic visceral pain. The P2X7 receptor is crucial in inflammatory processes and is closely connected to developing pain and depression. Gallic acid, a phenolic acid that can be extracted from traditional Chinese medicine, has been demonstrated to be anti-inflammatory and anti-depressive. In this study, we investigated whether gallic acid could alleviate comorbid visceral pain and depression by reducing the expression of the P2X7 receptor. To this end, the pain thresholds of rats with comorbid visceral pain and depression were gauged using the abdominal withdraw reflex score, whereas the depression level of each rat was quantified using the sucrose preference test, the forced swimming test, and the open field test. The expressions of the P2X7 receptor in the hippocampus, spinal cord, and dorsal root ganglion (DRG) were assessed by Western blotting and quantitative real-time PCR. Furthermore, the distributions of the P2X7 receptor and glial fibrillary acidic protein (GFAP) in the hippocampus and DRG were investigated in immunofluorescent experiments. The expressions of p-ERK1/2 and ERK1/2 were determined using Western blotting. The enzyme-linked immunosorbent assay was utilized to measure the concentrations of IL-1ß, TNF-α, and IL-10 in the serum. Our results demonstrate that gallic acid was able to alleviate both pain and depression in the rats under study. Gallic acid also reduced the expressions of the P2X7 receptor and p-ERK1/2 in the hippocampi, spinal cords, and DRGs of these rats. Moreover, gallic acid treatment decreased the serum concentrations of IL-1ß and TNF-α, while raising IL-10 levels in these rats. Thus, gallic acid may be an effective novel candidate for the treatment of comorbid visceral pain and depression by inhibiting the expressions of the P2X7 receptor in the hippocampus, spinal cord, and DRG.

Recent Studies on the Pharmacological Activities and Structural Modifications of Compound-K.

Ginsenosides, the essential active ingredients extracted from ginseng, have been well studied in the past several decades because of their numerous pharmacological properties including anti-tumor, anti-inflammatory, and anti-diabetic activities, as well as hepatoprotection, skin protection, and memory improvement, etc. Compound-K (CK) is the major metabolite derived from the deglycosylation of ginsenosides by intestinal bacteria and has been proved to be the actual active entity absorbed into the systemic circulation. In this review, we comprehensively elucidate the pharmacological activities of CK from the molecular mechanism, as well as its structurally modified derivatives. We hope this review would be helpful to get a systematic summary and provide constructive insights for the further research of CK.

Characterization of Bimanual Cyclical Tasks From Single-Trial EEG-fNIRS Measurements.

Robot-assisted bimanual training is promising to improve motor function and cortical reorganization for hemiparetic stroke patients. Closing the rehabilitation training loop with neurofeedback can help refine training protocols in time for better engagements and outcomes. However, due to the low signal-to-noise ratio (SNR) and non-stationary properties of neural signals, reliable characterization of bimanual training-induced neural activities from single-trial measurement is challenging. In this study, ten human participants were recruited conducting robot-assisted bimanual cyclical tasks (in-phase, 90° out-of-phase, and anti-phase) when concurrent electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) were recorded. A unified EEG-fNIRS bimodal signal processing framework was proposed to characterize neural activities induced by three types of bimanual cyclical tasks. In this framework, novel artifact removal methods were used to improve the SNR and the task-related component analysis (TRCA) was introduced to increase the reproducibility of EEG-fNIRS bimodal features. The optimized features were transformed into low-dimensional indicators to reliably characterize bimanual training-induced neural activation. The SVM classification results of three bimanual cyclical tasks revealed a good discrimination ability of EEG-fNIRS bimodal indicators (90.1%), which was higher than that using EEG (74.8%) or fNIRS (82.2%) alone, supporting the proposed method as a feasible technique to characterize neural activities during robot-assisted bimanual training.

Biodegradable mesoporous nanocomposites with dual-targeting function for enhanced anti-tumor therapy.

Tumor-associated macrophages (TAMs), the main components of infiltrating leukocytes in tumors, often play a key role in promoting cancer development and progression. The tumor-specific microenvironment forces the phenotype of tumor-infiltrating to evolve in a direction favorable to tumor development, that is, the generation of M2-like TAMs. Consequently, the dual intervention of cancer cells and tumor microenvironment has become a research hotspot in the field of tumor immunotherapy. In this contribution, we developed pH-sensitive mesoporous calcium silicate nanocomposites (MCNs) encapsulated with indocyanine green (ICG) to enable the effective combination of photothermal therapy (PTT) and photodynamic therapy (PDT) triggered by the 808 nm near-infrared (NIR) light. The mannose and hyaluronic acid-grafted MCNs specifically targeted TAMs and tumor cells and promoted cell apoptosis both in vitro and in vivo. This paper revealed that irradiation of ICG loaded MCNs with NIR can produce a potent hyperthermia and induce abundant intracellular singlet oxygen generation in the target cells. These results suggest that the novel nanoplatform is believed to facilitate the delivery of chemotherapeutic agents to the tumor microenvironment (TME) to enhance the effects of tumor treatment.

Berberine inhibits dendritic cells differentiation in DSS-induced colitis by promoting Bacteroides fragilis.

BACKGROUNDS: Berberine (BBR), a compound long used in traditional Chinese medicine, has been reported to have therapeutic effects in treating ulcerative colitis (UC), attributed to its anti-inflammatory properties and restorative potential of tight junctions (TJs). However, the mechanism by which BBR affects intestinal bacteria and immunity is still unclear. METHODS: This study investigated the effects of BBR on intestinal bacteria and the inflammatory response in dextran sulfate sodium (DSS)-induced colitis mice. Immunohistochemistry (IHC) and electron microscopy were used to detect intestinal TJs. Microflora analysis was used to screen for bacteria regulated by BBR. RESULTS: The results showed that BBR had increased colonic epithelium zonula occludens proteins-1 (ZO-1) and occludin expression and reduced T-helper 17/T regulatory ratio in DSS-induced mice. Mechanically, BBR eliminated DSS-induced intestinal flora disturbances in mice, particularly increased Bacteroides fragilis (B. fragilis) in vivo and in vitro. B. fragilis decreased the interleukin-6 induced by dendritic cells through some heat-resistant component rather than nucleic acids or proteins. CONCLUSIONS: Overall, these data suggest that BBR had a moderating effect on DSS-induced colitis. This compound may regulate intestinal immune cell differentiation by affecting the growth of B. fragilis, providing new insights into the potential application of BBR in UC.

Additional Benefits Conferred by Endoscopic Sclerotherapy to Liver Cirrhosis Patients Receiving Endoscopic Variceal Ligation.

OBJECTIVE: Gastroesophageal varices are a direct consequence of portal hypertension in cirrhosis. The management of gastroesophageal varices has evolved over the last decade resulting in reduced mortality and morbidity rates. The study was aimed to analyze the short-term and long-term efficacy of different endoscopic methods in the treatment of gastric varices in cirrhotic patients. METHODS: From January 2016 to December 2019, 135 patients with liver cirrhosis and gastric varices undergoing different endoscopic treatment protocols were retrospectively analyzed. The patients were divided into three groups according to endoscopic variceal ligation, endoscopic sclerotherapy, and a combination of both, respectively. Main outcomes including the overall response rate, hemostasis, short- and long-term rebleeding (3 months before and after treatment), complication, blood pressure, heart rate, portal venous pressure (PVP), portal vein diameter (PVD), portal vein velocity (PVV), portal vein blood flow (PVF) detected by ultrasound, recurrence rate, and mortality were analyzed after treatments. RESULTS: The overall response rate in the combined group was higher than that in the ligation group and the sclerotherapy group (P < 0.05). The incidence rate of complications in the combined group and the ligation group was lower than that in the sclerotherapy group (P < 0.05). After treatment, the PVP, PVD, and PVF were reduced in the combined group compared with the ligation group and the sclerotherapy group, while the PVV was not (P < 0.05). Lower rates of long-term rebleeding, recurrence, and mortality were noted in the combined group compared to the ligation group and the sclerotherapy group (P < 0.05). CONCLUSION: Endoscopic variceal ligation combined with endoscopic sclerotherapy is more effective than both alone in treating liver cirrhosis and gastric varices. The combined therapy contributed to reduced short-term and long-term rebleeding rate, decreased long-term recurrence rate, and mortality.

Do we need more patient-friendly treatment options for overactive bladder (OAB)?

AIMS: To collect feedback from subjects diagnosed with overactive bladder (OAB) on its impact on their quality of life, their satisfaction with current treatment options, and to assess nonsurgical, tibial nerve stimulation as a treatment option. METHODS: Subjects were asked a variety of questions about the impact of OAB on their lives, their satisfaction with current and previous treatment approaches. Subjects evaluated the comfort of a nonworking prototype garment and were given electrical stimulation over their posterior tibial nerve to assess comfort and tolerability. Electromyographic (EMG) signals were recorded. RESULTS: A total of 40 subjects with OAB symptoms were evaluated in the study. Urgency (55%), frequency (47.5%), nocturia (40%), and incontinence (30%) were the most bothersome symptoms. At the time of the study only 32.5% of the subjects were treating their OAB symptoms. Of those that had tried and discontinued treatments, most had failed medications (n = 14) due to no improvements or side effects. Only 2 subjects found stimulation to be uncomfortable before an EMG signal could be detected. The most common word used to describe the feeling of stimulation was "constant," followed by "tingling," "vibrating," and "comfortable." CONCLUSIONS: Most subjects who had tried OAB treatments were dissatisfied and discontinued their use. A new patient-friendly approach to OAB therapy that delivers efficacy but overcomes drawbacks associated with currently available treatments is needed. Subjects found electrical stimulation over the tibial nerve to be comfortable and tolerable and this should be considered as an alternative treatment approach for OAB.

Effect and Safety of Penetrating Moxibustion in Treatment of Migraine without Aura: A Randomized Controlled Trial.

OBJECTIVE: To observe the clinical effect of penetrating moxibustion on migraine without aura (MO) patients. METHODS: Totally 60 MO patients from the Acupuncture Clinic of the Third Affiliated Hospital of Henan University of Chinese Medicine were collected from November 2015 to February 2017. All patients were assigned to a treatment group and a control group using a random number table, 30 cases in each group. The treatment group was treated with penetrating moxibustion, and the control group was treated with mild moxibustion, thrice a week for 4 consecutive weeks. The total effective rate, Visual Analogue Scale (VAS) scores, headache intensity, and Migraine Specific Quality of Life Questionnaire (MSQ) scores of patients after treatment were compared between the two groups. The moxibustion sensation and reaction after moxibustion were observed, and the adverse reactions were evaluated. All patients were followed up at 4 and 16 weeks after treatment. RESULTS: The total effective rate of the treatment group was significantly higher than that of the control group (93.33% vs. 80.00%, P<0.05). The improvement of VAS scores, headache intensity, and the role restrictive and role preventive scores in MSQ in the treatment group was better than those in the control group (P<0.05). The person-time of moxibustion sensations of itching, numbness and cold as well as flushing and sweating after moxibustion in the treatment group was all significantly higher than that in the control group (P<0.01). There was no significant difference in safety evaluation between the two groups (P>0.05). CONCLUSIONS: Penetrating moxibustion can significantly relieve pain and improve quality of life of MO patients. After penetrating moxibustion, flushing and sweating of patients were obvious, and the curative effect was superior to the mild moxibustion.

Neuroprotective carbazole alkaloids from the stems and leaves of Clausena lenis.

The investigation on the stems and leaves of Clausena lenis led to the isolation of a previously undescribed carbazole alkaloid, clausenalenine A (1), along with seven known analogues (2-8). The structure of 1 was elucidated based on comprehensive spectroscopic analyses and the known compounds were identified by comparisons with data reported in the literatures. All known compounds (2-8) were isolated from C. lenis for the first time. All isolated compounds were evaluated for their neuroprotective activities against 6-hydroxydopamine induced cell death in human neuroblastoma SH-SY5Y cells in vitro. Compounds 1-8 showed significant neuroprotective effects with EC50 values ranging from 0.68 to 18.76 µM.