The therapeutic potential of berberine chloride against SARM1-dependent axon degeneration in acrylamide-induced neuropathy.

Chronic acrylamide (ACR) intoxication causes typical pathology of axon degeneration. Moreover, sterile-α and toll/interleukin 1 receptor motif-containing protein 1 (SARM1), the central executioner of the programmed axonal destruction process under various insults, is up-regulated in ACR neuropathy. However, it remains unclear whether inhibitors targeting SARM1 are effective or not. Among all the pharmacological antagonists, berberine chloride (BBE), a natural phytochemical and the first identified non-competitive inhibitor of SARM1, attracts tremendous attention. Here, we observed the protection of 100 µM BBE against ACR-induced neurites injury (2 mM ACR, 24 hr) in vitro, and further evaluated the neuroprotective effect of BBE (100 mg/kg p.o. three times a week for 4 weeks) in ACR-intoxicated rats (40 mg/kg i.p. three times a week for 4 weeks). The expression of SARM1 was also detected. BBE intervention significantly inhibited the overexpression of SARM1, ameliorated axonal degeneration, alleviated pathological changes in the sciatic nerve and spinal cord, and improved neurobehavioral symptoms in ACR-poisoned rats. Thus, BBE exhibits a strong neuroprotective effect against the SARM1-dependent axon destruction in ACR neuropathy. Meanwhile, our study underscores the need for appropriate inhibitor selection in diverse situations that would benefit from blocking the SARM1-dependent axonal destruction pathway.

Moxibustion regulates T-regulatory/T-helper 17 cell balance by modulating the microRNA-221/suppressor of cytokine signaling 3 axis in a mouse model of rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) progression is associated with the balance of T-regulatory (Treg) and T-helper 17 (Th17) cells, while the role of microRNAs (miRs) in regulating Treg/Th17 cell balance has not been clarified. This study aimed to assess whether moxibustion could regulate Treg/Th17 cell balance by modulating the miR-221/suppressor of cytokine signaling 3 (SOCS3) axis in the RA mouse model. METHODS: A mouse model of collagen-induced arthritis (CIA) was established in male DBA/1J mice. Twenty-two days after CIA induction, the mice received daily treatment with moxibustion for 12 times. Pathological scores were assessed according to the levels of synovial hyperplasia. The expression levels of cytokines interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-17 and IL-10 were analyzed in serum by enzyme-linked immunosorbent assay. The cluster of differentiation 4 (CD4+) splenocytes was analyzed by fluorescence-activated cell sorting. The expression levels of RA-related miRs and target genes were subsequently detected, and the target of miR-221 was confirmed by the dual-luciferase reporter assay. RESULTS: It was revealed that moxibustion treatment decreased the pathological scores and downregulated the expression levels of IL-1ß, IL-6, TNF-α, IFN-γ and IL-17, while upregulated the expression level of IL-10. The Treg/Th17 cell balance was regulated by moxibustion treatment. The expression level of miR-221 was suppressed by moxibustion treatment. Furthermore, SOCS3 was found as the direct target of miR-221, which mediated the function of moxibustion by regulating the Treg/Th17 cell balance. CONCLUSION: Moxibustion therapy regulated the Treg/Th17 cell balance by modulating the miR-221/SOCS3 axis in the RA mouse model.

Network Meta-Analysis of Acupoint Catgut Embedding in Treatment of Simple Obesity.

Objective: To evaluate the clinical efficacy of acupoint catgut embedding in the treatment of simple obesity through network meta-analysis. Methods: PubMed, Cochrane, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP database (VIP) were searched by using computer from 2011 to August 2021, and 35 RCT studies were retrieved. The quality of the literature was evaluated using the modified Jadad scoring table, and Stata 15.0 software was used for traditional meta-analysis and network meta-analysis. Results: Thirty-five RCTs (3040 cases in total) were included. Acupoint embedding, acupuncture, electroacupuncture, TCM, acupoint embedding + acupuncture, acupoint embedding + exercise diet therapy, acupoint embedding + TCM, exercise diet therapy, acupoint embedding + moxibustion, and acupoint embedding + cupping were investigated in the studies. The results of network meta-analysis were as follows: in terms of total effective rate, acupoint catgut embedding was superior to acupuncture, electroacupuncture, and exercise diet therapy (P < 0.05); electroacupuncture, acupoint catgut embedding + acupuncture, acupoint catgut embedding + exercise diet therapy, acupoint catgut + TCM, acupoint catgut + moxibustion, and acupoint catgut + cupping were superior to acupuncture (P < 0.05); acupoint catgut + moxibustion was superior to electroacupuncture (P < 0.05); acupoint catgut + TCM, acupoint catgut + moxibustion, and acupoint catgut + cupping were superior to TCM treatment (P < 0.05); and electroacupuncture, acupoint catgut, acupoint catgut + acupuncture, acupoint catgut + exercise diet therapy, acupoint catgut + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to sports diet therapy (P < 0.05). Regarding weight loss, acupuncture treatment was superior to acupoint catgut embedding therapy (P < 0.05); acupoint catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to acupuncture and electroacupuncture treatment (P < 0.05); acupoint catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, and acupoint catgut embedding + moxibustion were superior to TCM treatment (P < 0.05); and acupoint catgut embedding, acupoint catgut embedding + acupuncture, catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to exercise diet therapy (P < 0.05). In terms of BMI reduction, acupoint catgut embedding + moxibustion and acupoint catgut embedding + cupping were more evident than acupuncture treatment (P < 0.05); and acupoint catgut embedding + moxibustion was more evident than electroacupuncture treatment (P < 0.05). Conclusion: Acupoint catgut embedding and its combination with other therapies are the first choice for the treatment of simple obesity.

[Effect of oblique needling at Ashi-point on expression of MyoD1/Pax7 in mice with quadriceps femoris injury].

OBJECTIVE: To observe the effect of oblique needling at Ashi-point on behavior, and cell morphology, myogenic differentiation antigen (MyoD1) and paired box transcription factor Pax7 (Pax7) of quadriceps femoris tissue in quadriceps femoris injured mice. METHODS: A total of 24 C57BL/6 male mice were randomly divided into control, model, shallow insertion and deep insertion groups, with 6 mice in each group. The quadriceps femoris injury model was established by single intramuscular injection of 0.5% bupivacaine (BPVC). Twenty-four hours after modeling, mice of the two acupuncture groups were received oblique needling on the surface or through the muscle belly of quadriceps femoris for once, the oblique needling was lifted and inserted 3 times. The climbing pole test was conducted 24 h after modeling and 24 h after EA. Histopathological changes of quadriceps femoris was observed by H.E. staining. The expressions of MyoD1 and Pax7 were detected by immunohistochemistry. RESULTS: Compared with the control group, the score of climbing pole test was lower (P<0.01), and the expressions of MyoD1 and Pax7 significantly increased (P<0.01) in the model group. After the intervention and compared with the model group, the score of climbing pole test was higher (P<0.01), and the expressions of MyoD1 and Pax7 obviously increased (P<0.01) in the two acupuncture groups. The therapeutic effect of deep insertion group was apparently superior to that of shallow insertion group in up-regulating the climbing pole test score and expressions of MyoD1 and Pax7 (P<0.05, P<0.01). H.E. stain showed large areas of inflammatory infiltration, muscle cells swelling, atrophy, rupture, degeneration and necrosis, different cell sizes and morphologies, enlarged intervals, nuclear aggregation, deep nuclear staining, nuclear pyknosis, and hemorrhage in the model group, which was relatively milder in both needling groups. CONCLUSION: Oblique needling at Ashi-point can effectively promote the benign repair of injured quadriceps muscle and promote the recovery of exercise ability in mice, which may be associated with its effect in up-regulating the expression of MyoD1 and Pax7 protein. The role of deep insertion is superior to that of shallow insertion.

Research trends of prostatitis over past 20 years: A bibliometric analysis.

In the past two decades, thousands of documents in the field of prostatitis have been published. This bibliometric analysis aimed to assess the characteristics, hotspots and frontiers trend of global scientific output on prostatitis. With the trend of moderate growth, altogether 2,423 papers were reviewed. The leading role of the United States in global prostatitis research was obvious, while China had developed rapidly in recent years. Queen's University and JOURNAL OF UROLOGY were the most prolific affiliation and journal respectively. Nickel, J. C made the greatest contribution to the field of prostatitis. Five hotspots have been confirmed: (a) male infertility associated with prostatitis and the molecular mechanisms; (b) diagnosis and treatment of prostatitis; (c) inflammation, pain and bladder irritation symptoms; (d) relationship between chronic prostatitis/chronic pelvic pain syndrome, benign prostatic hyperplasia and prostate cancer; (e) epidemiology, complications of prostatitis and improvement of acupuncture. This bibliometric analysis reveals that the international cooperation was becoming more and more close. Hotspot analysis shows that the molecular mechanism of prostatitis will be a hotspot in the future, mainly focussing on inflammatory immunity and oxidative stress.

Zihuai recipe alleviates cyclophosphamide-induced diminished ovarian reserve via suppressing PI3K/AKT-mediated apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Zihuai recipe (ZHR), a Chinese herbal prescription, is widely used for the clinical treatment of Diminished ovarian reserve (DOR) infertility. However, little is known regarding its underlying mechanisms of DOR treatment. AIM OF THE STUDY: This study aimed to investigate the beneficial effects of ZHR on the treatment of DOR and to reveal the underlying mechanisms. MATERIALS AND METHODS: Sixty female 8-week-old Sprague-Dawley rats were randomly divided into the following six groups (n=10 per group): control, DOR, low-dose(2.7 g/kg/day) ZHR (L-ZHR), medium-dose(5.4 g/kg/day), ZHR (M-ZHR), high-dose(10.8 g/kg/day) ZHR (H-ZHR), and hormone replacement therapy (HRT) treatment groups. The DOR model was established in all the groups, except the control group, by a single intraperitoneal injection of 90 mg/kg cyclophosphamide. After the induction of the DOR model, rats were weighed and administered either the relevant dose of ZHR or an equal volume of saline solution (in the control and DOR groups). Rats in the HRT group received estradiol valerate tablets (0.16 mg/kg/day), and with medroxyprogesterone acetate tablets (0.86 mg/kg/day) added on day 4. After 32 days of treatment, the rats were euthanized and the ovaries were collected for sampling. Ovarian morphology was observed by hematoxylin and eosin staining and the number of follicles was counted under a microscope. The serum levels of anti-Müllerian hormone (AMH), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were quantified by ELISA. A TUNEL assay was used to analyze the level of apoptosis of the ovarian cells. The protein expressions of p-PI3K, p-AKT, PI3K, AKT, cleaved caspase-3, BAX, and Bcl-2 were measured by western blotting and immunohistochemistry. Data analysis was performed with SPSS 20.0 software. RESULTS: ZHR administration increased the ovarian index and the serum levels of AMH, GnRH, and E2, while lowering those of FSH and LH. ZHR treatment also increased the number of primordial, primary, secondary, and antral follicles, as well as the number of corpora lutea, but decreased the number of atretic follicles. Furthermore, ZHR administration decreased the percentage of TUNEL-positive ovarian cells. After treatment with ZHR, the protein expression levels of p-PI3K/PI3K, p-AKT/AKT, cleaved caspase-3 and BAX were decreased, whereas the level of Bcl-2 was increased. CONCLUSIONS: ZHR improved the ovarian reserve in CTX-induced DOR rats. The mechanisms of ZHR on DOR may be mediated through the regulation of gonadal hormones of the hypothalamic-pituitary-ovarian axis (HPOA), and the inhibition of PI3K/AKT-mediated apoptosis in granulosa cells.

An analysis of Treg/Th17 cells imbalance associated microRNA networks regulated by moxibustion therapy on Zusanli (ST36) and Shenshu (BL23) in mice with collagen induced arthritis.

Moxibustion is an emerging alternative therapy for rheumatoid arthritis (RA) in the eastern world, especially in China. However, the mechanism underlying this condition has not yet been elucidated. This study aimed to explore how moxibustion reduced arthritis by regulating Treg/Th17 cell imbalance and the role of differentiation-associated keynote microRNAs (miRNAs). Moxibustion therapy was administered to mice with collagen-induced arthritis (CIA). The arthritis index, histopathological changes, inflammatory factors, and Treg/Th17 cell balance were analyzed. MiRNAs from CD4+ T cells were analyzed based on the RNA-seq technology. Treg/Th17 cell differentiation-related miRNAs and their target genes were identified from the online database of miRDB, TargetScan, and miRTarBase. The expression of miRNAs and their target genes was verified by quantitative reverse transcription polymerase chain reaction and Western blot analysis. The binding sites of miRNAs and target genes were predicted by miRDB, and the targeting relationship between them was verified by dual-luciferase reporter assay. Arthritis in mice with CIA was reduced by moxibustion therapy, and Treg/Th17 cell imbalance was regulated. Seventeen upregulated and twenty-three downregulated miRNAs were identified in moxibustion-treated mice. Seven upregulated miRNAs, seven downregulated miRNAs, and five Treg/Th17 cell differentiation-associated target genes were predicted. Among them, miR-144-3p and Hif1a were suggested to be the keynote miRNA and target gene, respectively, regulating the Treg/Th17 cell differentiation. In conclusions, moxibustion therapy plays a possible regulatory function in rebalancing Treg/Th17 cells by regulating miR-144-3p and its target gene Hif1a to treat CIA.

Pretreatment of pig manure liquid digestate for microalgae cultivation via innovative flocculation-biological contact oxidation approach.

Liquid digestate with high concentration of organic matter and suspended solids cannot be directly used for microalgae cultivation. This study employed an innovative integrated approach, combining flocculation and biological contact oxidation (F-BCO), as a pretreatment to create a suitable environment for microalgae growth. The laboratory and pilot-scale experiments were both performed to verify operational performance. In F-BCO pretreatment, chemical oxygen demand (COD), NH3-N, and total phosphorus (TP) were reduced 55.0%, 46.1%, and 74.9%, respectively at pilot-scale in steady-state phase. It is further determined that the COD and TP removal were primarily attributed to flocculation, and NH3-N removal was mainly due to oxidation process (70%). The pretreated biogas slurry (BS) can be directly used for Chlorella cultivation, reaching a maximum accumulated biomass concentration of 3.3 g/L. The F-BCO process demonstrated a promising potential for pretreating BS to be a culture media for microalgae cultivation.

[Shenjing Guben Pills for repairing testicular spermatogenic injury induced by oxidative stress in rats].

OBJECTIVE: To investigate the antioxidative and spermatogenesis-repairing effects of Shenjing Guben Pills (SGP), a Chinese medicine for invigorating the kidney and blood circulation, on the testis, epididymis and sperm in rats with oxidative stress injury (OSI) induced by cadmium chloride. METHODS: Seventy-two male Wistar rats were equally randomized into six groups: normal control, OSI model control, Wuzi Yanzong Pills (WYP) and low-, medium- and high-dose SGP. The OSI model was made in the latter five groups by intraperitoneal injection of cadmium chloride at 1 mg/kg, and 24 hours later, the rats of the normal and model control groups treated intragastrically with 0.9% normal saline, those of the WYP group with WYP at 4.5 g/kg/d, and those of the low-, medium- and high-dose SGP groups with SGP at 2.8, 5.6 and 11.2 g/kg/d, respectively, all for 56 days. Then, all the animals were sacrificed for obtainment of the visceral indexes and histopathological changes of the testis, epididymis and seminal vesicle, measurement of sperm concentration and motility and the percentage of morphologically normal sperm (MNS) in the epididymis, and determination of the levels of glutathione perox-idase (GSH-PX), superoxide dismutase (SOD), malondial-dehyde aldehyde (MDA) and serum testosterone (T). RESULTS: Compared with the OSI model controls, the rats in the high-, medium- and low-dose SGP groups showed significantly higher visceral indexes of the testis (ï¼»0.237 ± 0.098ï¼½ vs ï¼»0.403 ± 0.090ï¼½, ï¼»0.357 ± 0.150ï¼½ and ï¼»0.348 ± 0.140ï¼½ g/100 g, P < 0.05) and seminal vesicle (ï¼»0.241 ± 0.118ï¼½ vs ï¼»0.347 ± 0.115ï¼½, ï¼»0.336 ± 0.090ï¼½ and ï¼»0.320 ± 0.065ï¼½ g/100 g, P < 0.05) and those of the high-dose SGP group in the epididymal index (ï¼»0.099 ± 0.088ï¼½ vs ï¼»0.156 ± 0.030ï¼½ g/100 g, P < 0.05). In comparison with the OSI model controls, the animals of the high-, medium- and low-dose SGP groups exhibited significant increases in sperm concentration (ï¼»10.5 ± 17.7ï¼½ vs ï¼»58.1 ± 32.2ï¼½, ï¼»36.0 ± 36.2ï¼½ and ï¼»31.9 ± 32.7ï¼½ ×106/ml, P < 0.05) and serum T (ï¼»2.56 ± 0.75ï¼½ vs ï¼»3.62 ± 0.96ï¼½, ï¼»3.48 ± 1.33ï¼½ and ï¼»3.24 ± 0.83ï¼½ nmol/L, P < 0.05 or P < 0.01), and those of the high- and medium-dose SCG groups in total sperm motility (ï¼»9.5 ± 13.0ï¼½% vs ï¼»26.5 ± 15.5ï¼½% and ï¼»18.9 ± 8.2ï¼½%, P < 0.05) and MNS (ï¼»36.2 ± 40.2ï¼½% vs ï¼»85.3 ± 23.3ï¼½% and ï¼»65.8 ± 28.1ï¼½%, P < 0.05) and the levels GSH-PX (ï¼»3.62 ± 2.22ï¼½ vs ï¼»5.70 ± 1.73ï¼½ and ï¼»5.42 ± 2.35ï¼½ U/mg prot, P < 0.05 ) and SOD (ï¼»41.3 ± 8.8ï¼½ vs ï¼»52.7 ± 14.6ï¼½ and ï¼»51.3 ± 14.7ï¼½ U/mg prot, P < 0.05). The MDA level, however, was markedly decreased in the high-, medium- and low-dose SGP groups (ï¼»0.41 ± 0.29ï¼½, ï¼»0.44 ± 0.19ï¼½ and ï¼»0.47 ± 0.20ï¼½ nmol/mg prot) as compared with that in the OSI model controls (ï¼»0.69 ± 0.28ï¼½ nmol/mg prot) (P < 0.05). Histopathological examinations manifested coagulative necrosis, calcification and disappearance of spermatogenic and Sertoli cells in the seminiferous tubules of the OSI model controls, with decreased intraluminal secretions and atrophic epithelial papillae in the seminal vesicles and non-sperm cells in the narrowed lumens of the atrophic epididymis. With the increased dose of SGP, the proportion of normal seminiferous tubules was enlarged, the epithelia of the seminal vesicle became column-shaped again, and the epididymal lumens grew lager with more sperm cells, which indicated a dose-dependent therapeutic efficacy. Medium- and high-dose SGP achieved a significantly better effect than WYP. CONCLUSIONS: Shenjing Guben Pills can antagonize oxidative stress, elevate the levels of testicular antioxidant enzymes and serum T, repair pathological injury of the testis, epididymis and seminal vesicle, and improve semen quality and spermatogenic function.

Augmentation effect of acupuncture on Bi'nao for hypophasis in patients with Bell's palsy: study protocol for a randomized controlled trial.

BACKGROUND: Hypophasis is one of the most frequently observed sequelae of patients with Bell's palsy, who have not recovered completely, creating a clinical difficulty for physicians. Acupuncture therapy has been widely used to treat Bell's palsy as a reasonable resolution for management of symptoms such as hypophasis. The number of acupuncture points (acu-points) is frequently selected in the approach of acupuncture therapy; however, whether these had high efficiency has not been proved. According to the literature review, Bi'nao was useful for treating eye and eye lipid diseases, which could be proved only by some successful cases. Thus, a randomized controlled trial was designed to evaluate the efficiency of the acu-point Bi'nao. METHODS/DESIGN: Participants with hypophasis as the major symptom are selected among patients with Bell's palsy and randomly allocated into one of the three groups at a 1:1:1 allocation ratio. All participants receive conventional acupuncture therapy; however, those assigned to the real acupuncture group will be given added acupuncture therapy on the acu-point Bi'nao, while those assigned to the sham acupuncture group were given extra acupuncture therapy on the sham Bi'nao as a placebo. The efficacy of the acupuncture therapy on the acu-point Bi'nao for hypophasis will be evaluated by Eye Crack Width Measurement (ECWM) and Eyelid Strength Assessment (ESA) before and after therapy. DISCUSSION: This is the first study assessing the safety and efficiency of Bi'nao in treating the hypophasis of patients with Bell's palsy that might support the application of this acupuncture therapy. However, evaluating hypophasis is challenging, and, thus, ECWM and ESA were applied to measure the eyelid movement. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR-INR-17012955 . Registered on 12 October 2017.

Is cupping blister harmful?-A proteomical analysis of blister fluid induced by cupping therapy and scald.

OBJECTIVE: Cupping therapy has a long history in traditional medicine especially in Asian countries. It was controversial whether cupping induced blisters are beneficial to healing effects, and the formation and content in the blisters remain unexplored. We aimed to identify and compare the molecular components of the blister fluid from the cupping therapy and the scalds to explore the necessary of inducing cupping induced blisters. METHODS: Fluid sample of blisters from fifteen patients receiving cupping therapy (Cupping group) and scald burns (Scald group) were collected in this study. Proteins from the blisters were separated by two-dimensional electrophoresis (2D-gel) and further analyzed by mass spectrometry. In addition, the changes in particular proteins were confirmed by Western blotting. RESULTS: The protein components are significantly different between blister from cupping therapy and scalds. The immune responses, oxidative stress and metabolic related proteins (Ig lambda-2 chain C regions, Ig gamma-1 chain C region, hemopexin, prdx2, calmodulin, succinyl-CoA ligase and tetranectin) were increased, whereas the hemoglobin subunit beta was decreased in the Cupping group compared with the Scald group. CONCLUSIONS: Cupping induced blisters contain several proteins which relate to the activation of certain immune pathways including anti-oxidation, anti-apoptosis, tissue repairing and metabolic regulation. This proteomic analysis may indicate a significant clue to the mechanism study of cupping.

[Effects of moxibustion on Treg/Th17 cell and its signal pathway in mice with rheumatoid arthritis].

OBJECTIVE: To observe the effects of moxibustion on Treg/Th17 imbalance and related signal pathway in mice with rheumatoid arthritis (RA), so as to explore the action mechanism of moxibustion on RA. METHODS: Twenty-four DBA/1J male mice were randomly divided into a normal group, a model group, a sham moxibustion group and a moxibustion group, 6 mice in each one. RA model was induced by subcutaneous injection of typeⅡcollagen and adjuvant at tail in mice other than the normal group. The mice in the moxibustion group were treated with moxibustion at"Zusanli" (ST 36) and "Shenshu" (BL 23), 1 mg per cone, 6 cones per acupoint. The consecutive 6-day treatment was taken as one course, and totally 2 courses were given with an interval of 2 d between courses. The mice in the sham moxibustion group were treated with immobilization as the moxibustion group. The effects of moxibustion on joint swelling was evaluated by RA scale of collagen induced arthritis (CIA); the pathological changes of joint inflammation were observed by HE staining; the cell count of Th17 and Treg in spleen was analyzed by flow cytometry; the content of cytokine IL-1ß, IL-6, IL-10, IL-17, IL-23, TGF-ß and Galectin-9 were analyzed by ELISA; the mRNA and protein expression of Foxp3, Galectin-9, RORγt, CARMA1, NF-κB were analyzed by Real-time PCR and Western Blotting method. RESULTS: Ten to 12 d after the secondary immune, red and swelling of ankle joint, feet and toe joint were observed, indicating successful establishment of RA model. 15 d into moxibustion treatment, the joint swelling was improved in the moxibustion group and the sham moxibustion group, which was superior in the moxibustion group (P<0.05). As for pathological changes, compare with the normal group, the articular surface was rougher and synovial layer thinner in the model group, which was recovered to a certain extent in the sham moxibustion group; the articular surface was smooth and synovial layer was thicker in the moxibustion group, which was similar to the normal group. The results of flow cytometry test indicated the cell count of Treg in the model group was reduced but that of Th17 was increased than the normal group (both P<0.01); the moxibustion could increase significantly the cell count of Treg (P<0.05), but no effect was observed on Th17 (P>0.05). The results of ELISA test indicated the differences of increasing of IL-1ß, IL-6, IL-17, IL-23, TGF-ßas well as the reducing of IL-10 were not significant between the sham moxibustion group and the moxibustion group (all P>0.05); moxibustion treatment could increase the content of Galectin-9 which was reduced in RA mice (P<0.05). The results of RT-PCR and Western blotting test indicated the mRNA and protein expression of Foxp3, Galectin-9 were reduced in the model group (all P<0.01), which could be up-regulated by moxibustion treatment (P<0.05, P<0.01); the mRNA and protein expression of RORγt, CARMA1, NF-κB was increased (all P<0.01), which could be down-regulated by moxibustion treatment (P<0.05, P<0.01). CONCLUSION: Moxibustion could improve the swelling of joint and inflammatory reaction of joint synovial in RA mice; the mechanism may be related to the regulation of Treg cells number in spleen and the expression of Foxp3, Galectin-9, RORγt, CARMA1, NF-κB, mRNA and protein expression.

Hazards of insomnia and the effects of acupuncture treatment on insomnia.

Insomnia is a common disease in modern society; it is made worse by increasingly fierce competition in the workplace and elsewhere, along with rapid economic and social development. Sleep disorders can result in changes in serum biomarkers and decreased immunity, and may cause maladies such as depression and cardiac diseases, as well as many other somatic symptoms. Western medications for treating insomnia can easily lead to addiction and other adverse effects. Fortunately, acupuncture can ease the symptoms of insomnia. This review summarizes the hazards associated with insomnia and the use of acupuncture in its treatment. Furthermore, the authors introduce an effective and low-cost method of treating insomnia with acupuncture. This review indicates that insomnia poses a major threat to mental health through its effects on serum components, heart function and the immune system of patients, which may lead to other physiological disorders. Anxiety and depression are the two main negative emotions affected by insomnia. Acupuncture, which has showed effectiveness against insomnia and its complications, may be an effective and complementary method for the treatment of insomnia and associated maladies.

Recovery of reducing sugars and volatile fatty acids from cornstalk at different hydrothermal treatment severity.

This study focused on the degradation of cornstalk and recovery of reducing sugars and volatile fatty acids (VFAs) at different hydrothermal treatment severity (HTS) (4.17-8.28, 190-320°C). The highest recovery of reducing sugars and VFAs reached 92.39% of aqueous products, equal to 34.79% based on dry biomass (HTS, 6.31). GC-MS and HPLC identified that the aqueous contained furfural (0.35-2.88 g/L) and 5-hydroxymethyl furfural (0-0.85 g/L) besides reducing sugars and VFAs. Hemicellulose and cellulose were completely degraded at a HTS of 5.70 and 7.60, respectively. SEM analysis showed that cornstalk was gradually changed from rigid and highly ordered fibrils to molten and grainy structure as HTS increased. FT-IR and TGA revealed the significant changes of organic groups for cornstalk before and after hydrothermal treatment at different HTS. Hydrothermal treatment might be promising for providing feedstocks suitable for biohythane production.

Effects of electroacupuncture therapy for Bell's palsy from acute stage: study protocol for a randomized controlled trial.

BACKGROUND: Although many patients with facial paralysis have obtained benefits or completely recovered after acupuncture or electroacupuncture therapy, it is still difficult to list intuitive evidence besides evaluation using neurological function scales and a few electrophysiologic data. Hence, the aim of this study is to use more intuitive and reliable detection techniques such as facial nerve magnetic resonance imaging (MRI), nerve electromyography, and F waves to observe changes in the anatomic morphology of facial nerves and nerve conduction before and after applying acupuncture or electroacupuncture, and to verify their effectiveness by combining neurological function scales. METHODS/DESIGN: A total of 132 patients with Bell's palsy (grades III and IV in the House-Brackmann [HB] Facial Nerve Grading System) will be randomly divided into electroacupuncture, manual acupuncture, non-acupuncture, and medicine control groups. All the patients will be given electroacupuncture treatment after the acute period, except for patients in the medicine control group. The acupuncture or electroacupuncture treatments will be performed every 2 days until the patients recover or withdraw from the study. The primary outcome is analysis based on facial nerve functional scales (HB scale and Sunnybrook facial grading system), and the secondary outcome is analysis based on MRI, nerve electromyography and F-wave detection. All the patients will undergo MRI within 3 days after Bell's palsy onset for observation of the signal intensity and facial nerve swelling of the unaffected and affected sides. They will also undergo facial nerve electromyography and F-wave detection within 1 week after onset of Bell's palsy. Nerve function will be evaluated using the HB scale and Sunnybrook facial grading system at each hospital visit for treatment until the end of the study. The MRI, nerve electromyography, and F-wave detection will be performed again at 1 month after the onset of Bell's palsy. TRIAL REGISTRATION: Chinese Clinical Trials Register identifier: ChiCTR-IPR-14005730. Registered on 23 December 2014.

Discovery of oral and inhaled PDE4 inhibitors.

The optimization of oxazole-based PDE4 inhibitor 1 has led to the identification of both oral (compound 16) and inhaled (compound 34) PDE4 inhibitors. Selectivity against PDE10/PDE11, off target screening, and in vivo activity in the rat are discussed.

[Rasch analysis on stroke-specific quality of life (SS-QOL) scale of acupuncture intervention on stroke].

OBJECTIVE: To optimize the evaluation level of active motor threshold and the functional domain of upper limbs of stroke-specific quality of life (SS-QOL) scale with Rasch analysis. METHODS: Sixty patients with acute ischemic stroke that were in accord with research criterid were randomly divided into a test group (30 cases) and a control group (30 cases). Acupuncture treatment and routine western medicine were applied on the test group, and single treatment of routine western medicine was applied on the control group. Selected acupoints were MS 5, Fengchi (GB 20), Hegu (LI 4), etc. Active motor threshold and the functional domain of upper limbs of SS-QOL were self-tested by patients after one treating course. The characteristics of the above mentioned items were tested with Rasch model. RESULTS: The statistical result on fitness of active motor threshold and the functional domain of upper limbs of SS-QOL showed that every reference of samples and items wosin accord with the Rasch model and has well inner reliability and validity. The Infit and Outfit MnSq values of active motor threshold and the functional domain of upper limbs of SS-QOL are basically between 0.5 and 1.5. CONCLUSION: The application of Rasch analysis on the assessment of patient reported outcome (PRO) has optimized the PRO scale (the activity and upper limb function domain of SS-QOL scale) and enhanced evaluation level of active motor threshold and the functional domain of upper limbs of SS-QOL scale.

[Effects of moxibustion on the expression of IL-1beta, IL-2, IL-6 mRNA and protein in the cerebral cortex in tumor-bearing mice].

OBJECTIVE: To investigate the effect of moxibustion on the expression of IL-1beta, IL-2 and IL-6 proteins and mRNA in the cerebral cortex in tumor-bearing mice so as to study its mechanism underlying immunomodulation. METHODS: Forty Balb/c mice were randomly divided into control, tumor-bearing, non-acupoint moxibustion (N-AM) and acupoint-moxibustion (AM) groups (n = 10/group). Moxibustion was applied to "Dazhui" (GV 14), once every other day for 6 times. The expression of IL-1beta mRNA, IL-2 mRNA and IL-6 mRNA was detected by in situ hybridization, and the immunoactivity of IL-1beta, IL-6 and IL-2 determined by immunohistochemistry. RESULTS: Compared to the control group, the expression levels of IL-1beta mRNA and IL-2 mRNA, IL-1beta and IL-2 in the cerebral cortex of the tumor-bearing group were down-regulated significantly (P < 0.05, P < 0.01), while those of IL-6 mRNA and IL-6 up-regulated significantly (P < 0.05). Compared to the tumor-bearing group, the expression of IL-1beta mRNA and IL-2 mRNA, IL-1beta and IL-2 in the cerebral cortex in AM group were increased considerably (P < 0.05, P < 0.01); while cortical IL-6 immunoactivity in N-AM group was decreased significantly (P < 0.05), and IL-6 mRNA had no significant change in N-AM group (P > 0.05). Comparison between AM and N-AM groups showed that the expression levels of cortical IL-1beta mRNA and IL-2 mRNA, and IL-1beta and IL-2 proteins of the former group were obviously higher than those of the later group (P < 0.05, P < 0.01); while the immunoactivity of cortical IL-6 of AM group was significantly lower than that of N-AM group (P < 0.05). No significant difference between AM and N-AM groups in the expression of IL-6 mRNA (P > 0.05). CONCLUSION: Moxibustion treatment can up-regulate the expression of cortical IL-1beta mRNA, IL-2 mRNA, IL-1beta and IL-2 proteins, and down-regulate the expression of IL-6 mRNA and IL-6 in tumor-bearing mice, which may contribute to its effect in improving the immunosuppressing state under tumor conditions.

[Influence of electroacupuncture and moxibustion and their treated mouse serum on the proliferation of the cultured splenetic CD4+ CD25+ regulatory T cells of tumor-bearing mice].

OBJECTIVE: To observe the effect of electroacupuncture (EA) and moxibustion of "Dazhui" (GV 14) on the proliferation levels of the splenetic CD4+ CD25+ regulatory T cells (Tregs) of H22 tumor-bearing mice in vitro. METHODS: Forty eight Balb/c mice were randomized into control, model, moxibustion and EA groups, with 12 cases in each. H22 tumor-bearing model was set up by hypodermic injection of H22 tumor cells (0.2 ml, 1 x 10(7) cells/ml). EA (2 Hz, 2 mA) was applied to "Dazhui" (GV 14) and left "Huantiao" (GB 30) for 20 min, and moxibustion was applied to "Dazhui" (GV 14) 2 moxa-cones every time. The treatment was given from the 2nd day on after innoculation of tumor cells, once every other day, 6 times altogether. After the treatment, the mice were killed by peeling off the eyeball and blood samples were collected to be separated into serum. Then, Tregs of the spleen tissues of Balb/c mice in different groups were isolated by using megnetic activated cell sorting (MACS) system to be cultured independently, and co-cultured with EA-treated serum and moxibustion-treated serum separately in culture fluid for 96 h, added with 3H-tritiate thymidine (TdR) in the culture-fluid 12 h before the end of culture, followed by collecting the cells and detecting their proliferation levels (count per minute, cpm) by using a lipid scintillation device. RESULTS: The proliferation level of Tregs in model group was elevated significantly compared to normal control group (P < 0.05), while in comparison with model group, those of Tregs of EA and moxibustion groups decreased considerably (P < 0.01). After separate application of the diluted acupuncture-treated serum and moxibustion-treated serum at 1 : 1 and 1 : 8 (not 1 : 16 and 1 : 32) to the cultured Tregs, their proliferation levels (cpm) in EA and moxibustion groups were obviously upregulated in comparison to those of normal control group (P < 0.05), and the cpm in EA group was significantly higher than that in model group (P < 0.05), suggesting a different action mechanism between acupuncture-moxibustion treatment and serum stimulation. CONCLUSION: EA of "Dazhui" (GV 14) and "Huantiao" (GB 30) and moxibustion of "Dazhui" (GV 14) can effectively downregulate the proliferation level of the cultured splenetic Tregs of the tumor bearing mice. EA-treated serum and moxibustion-treated serum diluted at 1 : 1 and 1 : 8 can evidently upregulate the proliferation level of Tregs in vitro.

[Dynamic changes in traditional Chinese medicine syndromes in patients with ischemic stroke treated by acupuncture].

OBJECTIVE: To explore the dynamic state of traditional Chinese medicine (TCM) syndromes in acute ischemic stroke patients within 30 days of onset when treated with acupuncture, and to analyze the discrimination effects of the functions based on "decision trees" in identification of TCM syndromes of ischemic stroke. METHODS: A total of 264 cases with acute ischemic stroke regularly treated by acupuncture were included. Unified syndrome questionnaire was made by document retrieval and expert advice. The syndrome elements of the patients with acute ischemic stroke were surveyed on any day of three time periods (days 0-3, 4-10 and 11-30). The study was performed on multi time dynamic state results and correlated factors of basic TCM syndromes of the 264 patients. Bayes discriminant function of four syndromes of acute ischemic stroke on the basis of "decision trees" was used for computing the rate of miscarriage justice by original test and cross-validation, and the discrimination effects of "decision trees" were evaluated too. RESULTS: Wind, phlegm, fire-heat, qi deficiency, blood stasis, and hyperactivity of yang due to yin deficiency syndromes were found in the patients with acute ischemic stroke treated by acupuncture on the first 30 days of onset, and the incidence rates were 80.7%, 68.9%, 52.7%, 50.8%, 29.2% and 25.0% respectively. The mean scores and incidence rates of the six syndromes decreased gradually on three-time-point, especially of blood stasis syndrome. The main combined-syndromes were two-syndrome, three-syndrome and four-syndrome, and three-syndrome was the most frequently encountered type. Single syndrome was not found in the patients with acute ischemic stroke on the first three days of onset. Two-syndrome combination types were wind-phlegm, wind-heat, wind combined with qi deficiency or phlegm stagnation due to qi deficiency, phlegm-heat and blood stasis combined with hyperactivity of yang due to yin deficiency, and the incidence rates were 54.5%, 42.8%, 40.9%, 39.4%, 35.6% and 3.8% respectively. The mean scores of phlegm and qi deficiency in high-age patients were higher than those in low-age patients. The mean score and incidence rate of qi deficiency in female patients were higher than those in male patients. The mean score of phlegm in female patients was higher than that in male patients. To simplify the "decision trees" composed of 21 items, the group of Bayes discriminant function including eight most significant items out of the original 21 items was set up. The discrimination effect of the eight items including reddish face, constipation, yellow tongue fur, short breath, bright-white or gray complexion, tinnitus, feverish palms and soles and scanty tongue fur was similar to that of the 21 items, and there was no significant difference between the two functions. CONCLUSION: Wind syndrome and phlegm syndrome are the major single syndromes occurring in acute ischemic stroke patients within 30 days of onset, and three-syndrome combination is the most frequent multiple syndrome type. After acupuncture treatment, some syndrome elements including wind, phlegm, fire-heat, qi deficiency, blood stasis, and hyperactivity of yang due to yin deficiency are gradually reduced, and combined syndrome type is gradually become simple. Eight syndrome element items including reddish face, constipation, yellow tongue fur, short breath, bright-white or gray complexion, tinnitus, feverish palms and soles and scanty tongue fur have important means in discriminating yin syndrome from yang syndrome and sthenia syndrome from asthenia syndrome.