Fecal Microbiota Transplantation Improves Clinical Symptoms of Fibromyalgia: An open-label, Randomized, Nonplacebo-Controlled Study.

Fibromyalgia (FM) is a complex and poorly understood disorder characterized by chronic and widespread musculoskeletal pain, of which the etiology remains unknown. Now, the disorder of the gut microbiome is considered as one of the main causes of FM. This study was aimed to investigate the potential benefits of fecal microbiota transplantation (FMT) in patients with FM. A total of 45 patients completed this open-label randomized, nonplacebo-controlled clinical study. The Numerical Rating Scale (NRS) scores in the FMT group were slightly lower than the control group at 1 month (P> 0.05), and they decreased significantly at 2, 3, 6, and 12 months after treatment (P < 0.001). Besides, compared with the control group, the Widespread Pain Index (WPI), Symptom Severity (SS), Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) scores were significantly lower in the FMT group at different time points (P < 0.001). After 6 months of treatment, there was a significant increase in serotonin (5-HT) and gamma-aminobutyric acid (GABA) levels (P < 0.001), while glutamate levels significantly decreased in the FMT group (P < 0.001). The total effective rate was higher in the FMT group (90.9%) compared to the control group (56.5%) after 6 months of treatment (P < 0.05). FMT can effectively improve the clinical symptoms of FM. With the close relations between the changes of neurotransmitters and FM, certain neurotransmitters may serve as a diagnostic marker or potential target for FM patients. PERSPECTIVE: Fecal microbiota transplantation (FMT) is a novel therapy that aims to restore the gut microbial balance and modulate the gut-brain axis. It is valuable to further explore the therapeutic effect of FMT on FM. Furthermore, certain neurotransmitters may become a diagnostic marker or a new therapeutic target for FM patients.

Association of different cell types and inflammation in early acne vulgaris.

Acne vulgaris, one of the most common skin diseases, is a chronic cutaneous inflammation of the upper pilosebaceous unit (PSU) with complex pathogenesis. Inflammation plays a central role in the pathogenesis of acne vulgaris. During the inflammatory process, the innate and adaptive immune systems are coordinately activated to induce immune responses. Understanding the infiltration and cytokine secretion of differential cells in acne lesions, especially in the early stages of inflammation, will provide an insight into the pathogenesis of acne. The purpose of this review is to synthesize the association of different cell types with inflammation in early acne vulgaris and provide a comprehensive understanding of skin inflammation and immune responses.

Clinical Effects and Safety of the Use of Methylene Blue for the Treatment of Lumbar Facet Joint Syndrome.

BACKGROUND: Lumbar facet joint syndrome (LFJS) has been suggested to be a main source of low back pain. Methylene blue (MB), an inhibitor of nitric oxide synthesis with potential analgesic and anti-inflammatory properties, has been widely applied for a variety of pain-related diseases. However, no studies have been conducted on the treatment of LFJS patients using MB. OBJECTIVES: The purpose of this study was to evaluate the therapeutic effects of intra-articular injection of MB on LFJS patients. STUDY DESIGN: A prospective, randomized, controlled clinical trial. SETTING: Department of pain, Shanghai East Hospital. METHODS: A total of 120 eligible patients with LFJS were randomly divided into an MB group and a control group. Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ-9) were used to evaluate the pre-operation and post-operation states of the patients, and adverse events were recorded. The patients participating in this study were followed up for a period of 6 months. RESULTS: A total of 104 patients were followed up for the entire 6 months period. The control group included 51 patients, and the MB group included 53 patients. In both groups, the NRS scores, ODI scores, PHQ-9 scores, and PSQI scores decreased at different time points after treatment, compared to baseline. Moreover, the NRS scores were significantly lower than that of the control group at 3 months and 6 months after operation (P < 0.05). The ODI, PSQI, and PHQ-9 scores of the MB group were also respective significantly lower than that of the control group at 3 months and 6 months after operation (P < 0.05). As for the clinical efficacy, the total effective treatment rate of the MB group was significantly higher than that of the control group at 6 months after the procedure (P < 0.05). On the first day after operation, the incidence of hyperglycemia in patients with diabetes in the MB group was significantly lower than that of the control group (P < 0.05). LIMITATIONS: Firstly, the patients enrolled were recruited from a single center, and the sample size was small. Secondly, the patients were only followed-up for a period of 6 months after treatment. Thirdly, double blinding was not used in the design of this research study. CONCLUSION: Ultrasound-guided intra-articular MB injection is a safe and effective therapy for patients with LFJS. Intra-articular injection with MB can significantly reduce pain intensity, improve patient lumbar function, pain-related depression and sleep quality, increase total effective rate with no severe adverse side effects.

Gating Effects for Ion Transport in Three-Dimensional Functionalized Covalent Organic Frameworks.

The development of bioinspired nano/subnano-sized (<2 nm) ion channels is still considered a great challenge due to the difficulty in precisely controlling pore's internal structure and chemistry. Herein, for the first time, we report that three-dimensional functionalized covalent organic frameworks (COFs) can act as an effective nanofluidic platform for intelligent modulation of the ion transport. By strategic attachment of 12-crown-4 groups to the monomers as ion-driver door locks, we demonstrate that gating effects of functionalized COFs can be activated by lithium ions. The obtained materials exhibit an outstanding selective ion transmission performance with a high gating ratio (up to 23.6 for JUC-590), which is among the highest values in metal ion-activated solid-state nanochannels reported so far. Furthermore, JUC-590 offers high tunability, selectivity, and recyclability of ion transport proved by the experimental and simulated studies.

Combining Ozonated Autohemotherapy with Pharmacological Therapy for Comorbid Insomnia and Myofascial Pain Syndrome: A Prospective Randomized Controlled Study.

Objective: To examine the efficacy and safety of ozonated autohemotherapy (O3-AHT) combined with pharmacological therapy for comorbid insomnia and myofascial pain syndrome (MPS). Materials and Methods: One hundred and eighteen patients were randomly divided into two groups: the control group (N = 50) and the O3-AHT group (N = 53). Patients in both groups were given the same pharmacological management for three weeks. Patients in the O3-AHT group were treated with ozonated autohemotherapy (the concentration of ozone was 20 µg/ml in the first week, 30 µg/ml in the second week, and 40 µg/ml in the third week) combined with pharmacological therapy. Primary (the insomnia severity index (ISI) and visual analogue scale (VAS)) and secondary outcomes (the Epworth sleepiness scale (ESS), polysomnography data, the anxiety and preoccupation about sleep questionnaire (APSQ), the beck depression index (BDI), and the multidimensional fatigue inventory (MFI)) were examined at pretreatment, posttreatment, 1 month, and 6 months. Results: Fifty patients in the control group and fifty-three patients in the O3-AHT group completed the study. In both groups, insomnia and pain symptoms were relieved significantly compared with pretreatment. Compared with the control group, the O3-AHT group had significantly improved sleep quality, pain, and negative mood at different time points. No adverse complications were observed in either group. Conclusion: Compared with pharmacological therapy alone, ozonated autohemotherapy combined with pharmacological therapy can ameliorate insomnia, reduce pain intensity, improve negative mood, and alleviate fatigue more effectively without serious adverse complications.

Polyphyllin I Inhibits Propionibacterium acnes-Induced IL-8 Secretion in HaCaT Cells by Downregulating the CD36/NOX1/ROS/NLRP3/IL-1ß Pathway.

Acne vulgaris (AV) is a chronic skin disease involving inflammation of the pilosebaceous units. Propionibacterium acnes (P. acnes) hypercolonization is one pathogenic factor for AV. P. acnes that triggers interleukin-1ß (IL-1ß) by activating the pyrin domain-containing 3 protein (NLRP3) inflammasome of the NOD-like receptor family in human monocytes. Reactive oxygen species (ROS) acts as a trigger for the production of IL-8 and activates theNLRP3 inflammasome. IL-8 promotes the metastasis and multiplication of different cancerous cells, whereas keratinocyte proliferation and migration contribute to the progression of AV. A steroidal saponin called polyphyllin I (PPI) that is extracted from Paris polyphylla's rhizomes has anti-inflammatory properties. This study investigates the regulatory role of P. acnes in the secretion of IL-8 mediated by the CD36/NADPH oxidase 1 (NOX1)/ROS/NLRP3/IL-1ß pathway and the effects of PPI on the CD36/NOX1/ROS/NLRP3/IL-1ß/IL-8 pathway and human keratinocyte proliferation and migration. HaCaT cells were cultured and stimulated with 108 CFU/ml of P. acnes for 0, 6, 12, 18, 24, 30, and 36 hours. P. acnes induced IL-8 secretion from HaCaT cells via the CD36/NOX1/ROS/NLRP3/IL-1ß pathway. PPI inhibited the CD36/NLRP3/NOX1/ROS/IL-8/IL-1ß pathway and HaCaT cell proliferation and migration. PPI alleviates P. acnes-induced inflammatory responses and human keratinocyte proliferation and migration, implying a novel potential therapy for AV.

Ultrasound-Guided Continuous Thoracic Paravertebral Infusion of Methylene Blue in the Treatment of Postherpetic Neuralgia: A Prospective, Randomized, Controlled Study.

INTRODUCTION: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster. Methylene blue (MB) is an inhibitor of nitric oxide synthesis with potentially analgesic and anti-inflammatory properties. Studies have demonstrated that thoracic paravertebral single MB injection is effective in treating chronic pain. However, there are rare reports of the efficacy of continuous thoracic paravertebral infusion of MB for pain management in PHN patients. The purpose of this study was to evaluate the therapeutic effects of continuous thoracic paravertebral infusion of MB on PHN. METHODS: A total of 104 PHN patients were randomly divided into two groups: the control group (continuous thoracic paravertebral infusion of 5% lidocaine in a total volume of 300 ml) and the MB group (continuous thoracic paravertebral infusion of 5% lidocaine plus 0.2% MB in a total volume of 300 ml). All patients were evaluated using the Numerical Rating Scale (NRS), Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), 36-Item Short-Form Health Survey (SF-36), and medication doses before and after the procedure. The effective treatment rate and adverse complications were recorded 6 months after the procedure. RESULTS: In both groups, the NRS scores, ISI scores, PHQ-9 scores, and rescue medication dosages were significantly decreased at different time points after treatment compared to baseline, while the SF-36 scores were evidently improved at different time points after treatment compared to baseline. Compared with the control group, the MB group had significantly reduced NRS scores, ISI scores, PHQ-9 scores, and rescue medication dosages at each observation time point. Furthermore, the SF-36 scores in the MB group were significantly higher than those in the control group at each observation time point. The total effective treatment rate of the MB group was higher than that of the control group 6 months after the procedure. No severe adverse complications were observed in either group. CONCLUSIONS: Ultrasound-guided continuous thoracic paravertebral infusion with MB is a safe and effective therapy for PHN. Continuous infusion with MB can significantly reduce pain intensity, improve pain-related depression, increase quality of life, and decrease the amount of rescue medicine with no serious adverse complications.

Knockdown of H19 Inhibits the Pathogenesis of Acne Vulgaris by Targeting the miR-196a/TLR2/NF-κB Axis.

Acne vulgaris (AV) is a chronic inflammatory disease of the pilosebaceous unit, and Propionibacterium acnes (P. acnes) has been implicated in acne inflammation. Numerous studies have shown that non-coding RNAs play important roles in regulating the pathophysiological processes of acne. In addition, the first imprinted long non-coding RNA (lncRNA) identified, H19, plays a critical role in inflammatory disease. However, the expression and role of H19 in AV remain unclear. In this study, we investigated the effects of H19 in keratinocytes and explored the regulatory mechanisms underlying these effects. H19 was upregulated in keratinocytes treated with P. acnes in a concentration-dependent manner. The phosphorylated forms of the nuclear factor (NF)-κB-related proteins IκBα (p-IκBα) and p65 (p-P65) were significantly upregulated after P. acnes treatment. Additionally, secretion of the proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 was upregulated in a concentration-dependent manner. Knockdown of H19 inhibited the expression of p-IκBα and p-P65 as well as the secretion of TNF-α, IL-6, and IL-8 in keratinocytes treated with P. acnes. Moreover, H19 was found to exert its proinflammatory effects by activating NF-κB. H19, which was localized mainly in the cytoplasm of keratinocytes, facilitated Toll-like receptor 2 (TLR2) expression by acting as a miR-196a sponge. H19 thus promoted the activation of NF-κB and the secretion of inflammatory cytokines through the miR-196a/TLR2 axis. These findings provide novel insight into the pathogenesis of AV.

Piceatannol Inhibits P. acnes-Induced Keratinocyte Proliferation and Migration by Downregulating Oxidative Stress and the Inflammatory Response.

The Cutibacterium acnes (also called Propionibacterium acnes, P. acnes)-induced proliferation and migration of keratinocytes contribute to acne vulgaris (AV), which is a common inflammatory skin disease that causes physical and psychological impairments. Piceatannol (3, 5, 3', 4'-tetrahydroxy-trans-stilbene, PCT) is naturally present in many human diets and plays antioxidant and anti-inflammatory roles that inhibit cell proliferation and migration. We aimed to analyse the functions and underlying mechanisms of PCT in P. acnes-stimulated keratinocytes. First, PCT showed no toxicity against the normal human keratinocyte cell line HaCaT but inhibited P. acnes-induced HaCaT cell proliferation. Next, PCT promoted the nuclear translocation and target gene transcription of the antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), thereafter decreasing intracellular reactive oxygen species (ROS) levels. In addition, PCT inhibited the nuclear translocation of p65 [a subunit of nuclear factor kappa B (NF-κB)] and the secretion of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and interleukin-8 (IL-8). Finally, a transfection assay showed that PCT inhibited P. acnes-induced HaCaT cell proliferation and migration by activating the antioxidant Nrf2 pathway and inhibiting the inflammatory NF-κB pathway. Our data suggested that PCT alleviated P. acnes-induced HaCaT cell proliferation and migration through its antioxidant and anti-inflammatory roles, suggesting the potential of PCT to treat AV.

Proteomic Analysis and Functional Studies of Baicalin on Proteins Associated with Skin Cancer.

Abundant evidence supports the key role of ultraviolet radiation (UVR) in skin cancer development. The human skin, especially the epidermal layer, is the main defense against UV radiation. Baicalin is a major bioactive component of Scutellaria baicalensis Georgi, a plant which has been found to exhibit antitumor activity. The anticarcinogenic mechanism of baicalin is not completely understood. We have reported that baicalin inhibited UVB-induced photo-damage and apoptosis in HaCaT cells (human skin keratinocytes). The aim of the present study is to investigate the cellular gene targets responsible for baicalin's antitumor activity by performing two-dimensional electrophoresis liquid chromatography-mass spectrometry/mass spectrometry (2-DE LC-MS/MS) with HaCaT cells following UVB and baicalin exposure. Two-DE for protein separation was performed, followed by matrix-assisted laser desorption/ionization mass spectrometry and database searches. Nucleophosmin (NPM)-specific siRNA was designed and synthesized, and the small interfering RNA was transfected into skin squamous cancer A431 cells to knockdown the NPM expression. Proliferation and cell cycle status were assessed by CCK8 and flow cytometric analyses, respectively. We have identified 38 protein spots that are differentially expressed in HaCaT cells exposed to baicalin and/or UVB irradiation These proteins are involved in detoxification, proliferation, metabolism, cytoskeleton and motility. In particular, we found several proteins that have been linked to tumor progression and resistance, such as NPM. Baicalin treatment reduced the cellular proliferation rate and induced arrest during the S-phase of the cell cycle in A431 cells. NPM1 silencing significantly enhanced the effect of baicalin. Our data indicated that baicalin results in the significant inhibition of tumor growth in the A431 cell line, which may be associated with the regulation of the NPM gene expression.

[Law of the meridian abnormality based on the effectiveness of electroacupuncture for severe functional constipation].

OBJECTIVE: To observe the law of the meridian abnormal changes and the correlation with acupuncture efficacy based on the effectiveness study of electroacupuncture (EA) in treatment of severe functional constipation. METHODS: Seventy patients of severe functional constipation were randomized into an EA group and a sham-EA group, 35 cases in each one. In the EA group, Tianshu (ST 25) and Fujie (SP 14) were punctured deeply and stimulated with EA (dense-disperse wave, 2Hz/15 Hz, 0. 1 to 1. 0 mA), and Shangjuxu (ST 37) was needled. In the sham-EA group, the sites lateral to Tianshu (ST 25) and Fujie (SP 14) were punctured shallowly and stimulated with electricity. The site lateral to Shangjuxu (ST 37) was punctured shallowly. The treatment was given continuously for 8 weeks in the two groups, 5 times weekly in the first 2 weeks and 3 times weekly in the rest 6 weeks. WANG Juyi's meridian examination method was applied to detect the abnormalities of the spleen, stomach and large intestine meridians before treatment, and in 2, 4, 6 and 8 weeks among 70 patients separately. The frequency of complete spontaneous bowel movement (CSBM) every two weeks, meridian abnormal value and the relativity with CSBM change rate were compared in the patients between two groups. RESULTS: Regarding the increase of CSBM frequency, the effect started since the 2nd week in the EA group, with the treatment going on, CSBM frequency was increased apparently (all P<0. 05). In the sham-EA group, after 6 and 8-weeks of treatment, CSBM frequency was increased apparently as compared with that before treatment (all P<0. 05). The increase of CSBM frequency in the EA group was remarkably as compared with the sham-EA group at every time point (all P<0. 05). The abnormal value of the large intestine meridian in 2 weeks of treatment and the values of the stomach and spleen meridians and the relevant meridians in 4 weeks of treatment were all reduced apparently as compared with those in the baseline in the EA group (all P<0. 05). With the treatment time going on, the abnormal reflections on the large intestine and stomach meridians were reduced gradually (all P<0. 05), and the total change rate of abnormalities on the large intestine, stomach and spleen meridians presented the negative correlation with the total change rate of CSBM frequency (P<0. 01, P<0. 05). CONCLUSION: In the EA group, the efficacy on CSBM frequency in severe functional constipation is advantageous and stable as compared with the sham-EA group. Acupuncture at the relevant acupoints of the spleen, stomach and large intestine meridians achieves the definite regulation to the meridian abnormalities. It is discovered that the abnormal changes in the spleen, stomach

[Study on relationship between length of homologous sequences and chromosomic recombination rate in Saccharopolyspora erythraea].

In order to study the relationship between lengths of homologous fragments and chromsomic recombination rate in Saccharopolyspora erythraea, three homologous sequences, with mutant loci and different flanking sequences, (26bp + 27bp), (500bp + 576bp) and (1908bp + 1749bp), were synthesized by chemical reaction or PCR amplification, and cloned into pWHM3 to construct homologous recombination plasmids, pWHM1113, pWHM1116 and pWHM1119. When the plasmids were transformed into protoplast of Saccharopolyspora erythraea A226 under PEG mediated, on an average 30, 69 and 170 transformants grew on each plate for the three plasmids respectively, but chromosomic integration frequency were 0, 2% and 19% among corresponding transformants. Both pWHM1116 and pWHM1119 could take double crossover recombination, and exchange the mutant loci in the chromosome. It was concluded that when the flanking sequences were equal or more than (500bp + 576bp), they could take effective single and double recombination with Saccharopolyspora erythraea chromosome.