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Background. Electroacupuncture (EA) may have a role in the treatment of diarrhea symptoms. However, the efficacy and safety of EA with different current intensities in improving gastrointestinal function, psychology, and quality of life (QOL) of functional diarrhea (FD) remain unknown. Objective. To investigate the efficacy and safety of EA with different current intensities in improving gastrointestinal function, psychology, and QOL for FD patients. Methods. 73 FD patients were randomly divided into three groups: low current intensity group (LI) of EA, high current intensity group (HI) of EA, and loperamide control group (LC). Four weeks of treatment were provided in the three groups. The primary outcome was the proportion of normal defecation. Additional outcomes included the change from baseline for the weekly spontaneous bowel movements (SBMs) and the change from baseline for the mean Bristol Stool Form Scale (BSFS). QOL was assessed by the 36-item short-form health survey (SF-36). Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were used to assess the psychology state. Results. Low current intensity of EA significantly improved the proportion of normal defecation during treatment and follow-up period ( P < 0.01 ). EA significantly improves the mean BSFS scores and weekly SBMs, and this efficacy is equivalent to loperamide ( P < 0.05 ). The SF-36 scores of general health in LI and HI groups and vitality and mental health in LI group were significantly increased compared to baseline ( P < 0.05 ). Low current intensity of EA can significantly improve SAS and SDS scores ( P < 0.05 ). Conclusions. EA significantly improved stool consistency and weekly SBMs in FD patients. Compared with loperamide, low current intensity of EA may have a better sustainable effect in restoring normal defecation in patients with FD, and it can also effectively improve QOL, anxiety, and depression. However, larger sample sizes are needed to determine safety and efficacy. Trial registration number: NCT01274793.

Chinese herbal prescription JieZe-1 is effective for genital herpes with no visible adverse effects clinically. It showed an excellent anti-HSV-2 effect in vitro. However, its mechanism of anti-HSV-2 effect in vivo remains unclear. This study was designed to evaluate the anti-HSV-2 effect of JieZe-1 and berberine in a genital herpes mouse model and explore the underlying mechanism. The fingerprint of JieZe-1 was determined by high-performance liquid chromatography. First, we optimized a mouse model of genital herpes. Next, the weight, symptom score, morphological changes, viral load, membrane fusion proteins, critical proteins of the Toll-like receptor signaling pathway, cytokines, and immune cells of vaginal tissue in mice at different time points were measured. Finally, we treated the genital herpes mouse model with JieZe-1 gel (2.5, 1.5, and 0.5 g/ml) and tested the above experimental indexes at 12 h and on the 9th day after modeling. JieZe-1 improved the symptoms, weight, and histopathological damage of genital herpes mice, promoted the keratin repair of tissues, and protected organelles to maintain the typical morphology of cells. It downregulated the expression of membrane fusion proteins, critical proteins of the Toll-like receptor signaling pathway, cytokines, and immune cells. The vaginal, vulvar, and spinal cord viral load and vaginal virus shedding were also significantly reduced. In summary, JieZe-1 shows significant anti-HSV-2 efficacy in vivo. The mechanism is related to the inhibition of membrane fusion, the Toll-like receptor signaling pathway, inflammatory cytokines, and cellular immunity. However, berberine, the main component of JieZe-1 monarch medicine, showed no efficacy at a concentration of 891.8 μM (0.3 mg/ml).

The neuroinflammatory response induced by microglia plays a vital role in causing secondary brain damage after traumatic brain injury (TBI). Previous studies have found that the improved regulation of activated microglia could reduce neurological damage post-TBI. Phillyrin (Phi) is one of the main active ingredients extracted from the fruits of the medicinal plant Forsythia suspensa (Thunb.) with anti-inflammatory effects. Our study attempted to investigate the effects of phillyrin on microglial activation and neuron damage after TBI. The TBI model was applied to induce brain injury in mice, and neurological scores, brain water content, hematoxylin and eosin staining and Nissl staining were employed to determine the neuroprotective effects of phillyrin. Immunofluorescent staining and western blot analysis were used to detect nuclear factor-kappa B (NF-κB) and peroxisome proliferator-activated receptor gamma (PPARγ) expression and nuclear translocation, and the inflammation-related proteins and mRNAs were assessed by western blot analysis and quantitative real-time PCR. The results revealed that phillyrin not only inhibited the proinflammatory response induced by activated microglia but also attenuated neurological impairment and brain edema in vivo in a mouse TBI model. Additionally, phillyrin suppressed the phosphorylation of NF-κB in microglia after TBI insult. These effects of phillyrin were mostly abolished by the antagonist of PPARγ. Our results reveal that phillyrin could prominently inhibit the inflammation of microglia via the PPARγ signaling pathway, thus leading to potential neuroprotective treatment after traumatic brain injury.

Supplemental material, AIM818289_Supplemental_material_SP1 for Acupuncture for chronic fatigue syndrome: a systematic review and meta-analysis by Qing Zhang, Jing Gong, Haoxu Dong, Shabei Xu, Wei Wang and Guangying Huang in Acupuncture in Medicine

Ethnophamacological relevance The Chinese herbal prescription JieZe-1 (JZ-1) is based on the modification of Yihuang Tang, which was first described in Fu Qingzhu Nvke by the famous Qing Dynasty doctor Shan Fu as a treatment for leukorrheal diseases. As an in-hospital preparation, JZ-1 has been used in Tongji Hospital for many years to treat various infectious diseases of the lower female genital tract, including cervicitis, vaginitis, genital herpes and condyloma acuminatum. Our previous studies have shown that JZ-1 has curative effects on Candida albicans, Trichomonas vaginalis and Ureaplasma urealyticum infections. Aim of the study Genital herpes is among the most common sexually transmitted diseases (STDs) worldwide and is mainly caused by herpes simplex virus type-2 (HSV-2). Current therapies can relieve symptoms in patients but do not cure or prevent the spread of the virus. This study was designed to investigate the effect of JZ-1 on HSV-2 infection and its mechanism, which is based on autophagy induction, to provide new ideas and a basis for the study of antiviral drugs. Materials and methods Evaluation of the antiviral activity of JZ-1 was conducted by MTT assay and western blotting. Then, Western blot and immunofluorescence analyses, observations through transmission electron microscopy and experiments with the recombinant lentivirus vector mRFP-GFP-LC3B were used to monitor autophagic flux in VK2/E6E7 cells. To explore the mechanism by which JZ-1 regulates autophagy, western blotting and real-time quantitative PCR (qRT-PCR) were used to determine the expression of phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway proteins and to detect changes in critical molecules in the pathway after the application of a PI3K inhibitor. Additionally, the mRNA expression levels of inflammatory cytokines, namely, IL-6, IFN-α, IFN-β and TNF-α, were measured with qRT-PCR. Results HSV-2 infection inhibited autophagy in the VK2/E6E7 cells. Further study revealed that the activation of the PI3K/Akt/mTOR pathway induced by HSV-2 infection may result in the blocked autophagic flux and inhibited autophagosome and autolysosome formation. JZ-1 exhibited significant antiviral activity in the VK2/E6E7 cells, which showed increased cell vitality and reduced viral protein expression, namely, earliest virus-specific infected cell polypeptides 5 (ICP5) and glycoprotein D (gD). We found that JZ-1 treatment inhibited the upregulation of the PI3K/Akt/mTOR pathway proteins and promoted autophagy to combat HSV-2 infection, while PI3K inhibitor pretreatment prevented the enhanced autophagy induced by JZ-1. Moreover, JZ-1 attenuated the increase in inflammatory cytokines that had been induced HSV-2 infection. Conclusion Our results showed that JZ-1 protects against HSV-2 infection, and this beneficial effect may be mediated by inducing autophagy via inhibition of the PI3K/Akt/mTOR signaling axis., Graphical abstract Image 1

Background: The most frequently used spermicide Nonoxynol-9 (N-9) in the clinic alters the vaginal flora, which will result in an increased risk of opportunistic infection. So development of a novel spermicidal and microbicidal drug appears to be inevitable. Vaginal local immune is an important part of vaginal flora. Secretory leukocyte protease inhibitor (SLPI), surfactant proteins D (SP-D), and lactoferrin (LF) are anti-microbial molecules with important roles in immune system of female vaginas. Objective: To observe effect of a vaginal spermicide nonoxynol-9 (N-9) berberine plural gel on the expression of SLPI SP-D and LF in mice’s vaginas. Materials and Methods : Female BABL/C mice were randomly divided into following 5 groups: normal control group, blank gel group, berberine gel group, 12% N-9 gel group and N-9 berberine plural gel group. Estradiol benzoate at physiological dose was done by hypodermic injection to every group’s mice. After 72h, drug gels were separately injected into the mice’s vaginas, while immunohistochemistry and Western blot were taken to detect the expression of the 3 indexes in mice’s vaginas respectively after 24h and 72h of gel injection. Results: The differences in the three indexes between normal control group and blank gel group were not significant statistically (p>0.05). The expression of the three indexes in 12% N-9 gel group was decreased compared to that in blank gel group (p0.05). Also, the three index's level of 24h and 72h in sub observation groups after treatment were without statistical significance (p>0.05). Conclusion: Application of N-9 berberine plural gel had little impact on antimicrobial peptides in normal mice’s vaginas.

Here we report the complete recovery from Bell's palsy (BP) of a 27-year-old woman, 27 weeks pregnant, after 2 weeks of acupuncture treatment. BP in pregnancy is an acute idiopathic peripheral facial paralysis of unknown etiology. Treatment and management have not been well evaluated or documented in the literature. The patient was exposed to wind and cold weather before the rapid onset of BP on December 26, 2008. She was treated with acupuncture without co-intervention. During the first week, needles were gently manipulated at local and distal acupoints to induce the qi sensation, and direct moxibustion with moxa sticks was performed at two points, Yangbai (GB14) and Dicang (ST4). During the second week, needles were manipulated without inducing the qi sensation, and moxibustion was performed as previously explained. To document progress, the patient was videotaped before, during, and after each treatment. Outcome assessments included the House-Brackmann facial nerve grading system (HBS), the Nottingham facial nerve grading system, and the Facial Disability Indexes (FDIP). Prior to treatment, her HBS was II, Nottingham was 50.88%, and FDIP was 90. After 2 weeks, her symptoms had disappeared, her face was restored to normal, HBS was I, Nottingham was 96.46%, and FDIP was 100. These results suggest that acupuncture may be a safe, alternative treatment for BP in pregnancy.

In order to observe the effect of Bushenantai recipe on the expression of endometrial leukemia-inhibitory factor (LIF) in mice with embryonic implantation dysfunction (EID), 120 Kunming mice post coition were randomized into three groups: normal control group, model group and traditional Chinese medicine group (TCM group) (n=40 in each group). Uterus was collected on the pregnancy day (Pd) 4, 5, 6 after an intravenous injection of Evan's blue. The endometrium was dyed by Evan's blue and the mean points of response were observed on Pd 5. The expression of LIF mRNA and protein was detected by RT-PCR and immunohistochemistry respectively and analyzed statistically by image system. The results showed that the number of implantation sites in model group was remarkably less than in normal control group and TCM group. There was no significant difference between normal control group and TCM group. The expression of LIF mRNA and protein in model group was delayed. Bushenantai recipe could increase the expression of LIF mRNA and protein in endometria of mice with EID. It was suggested that Bushenantai recipe could improve embryo implantation of mice with EID by promoting the endometrial LIF expression and endometrial decidualization.

Objective: To explore the therapeutic effect and the possible working mechanism in using Chinese herbal medicine (CHM) for supplementing Kidney and Qi, and activating blood circulation in treating intrauterine growth retardation of fetus (IUGR). Methods: Fifty-five cases of IUGR were divided into two groups, 30 cases in the CHM group treated with CHM and the 25 in the control group treated with amino acids. The effect of CHM treatment was observed and compared with that of the control group, normal pregnancy group and non-treated IUGR group. Results: Body weight of the newborns in the CHM was markedly higher than that in the control group. Not only the maternal fundal height (FH) and the abdominal circumference (AC), but also the fetal growth parameters, including biparietal diameter, head circumference (HC), and femur length (FL) in the CHM group increased much faster than those in the control group. After CHM treatment, the maternal serum levels of estriol (E3) and human placental lactogen (hPL) approached to those in the normal pregnancy group, but the control group, in comparison with the normal pregnancy group, was significantly different. The umbilical venous plasma concentration of essential amino acids in both treated groups improved, but the improvement in the CHM group was more significant than that in the control group. No apparent adverse effect of CHM was observed in either mother or fetus. Conclusion: CHM for supplementing Kidney and Qi and activating blood circulation was more effective in improving placental function and enhancing amino acid transportation than amino acid.

To observe the effect of acupuncture on CXCL8 receptors (CXCR1 and CXCR2) in rat endometrium experiencing embryo implantation failure, 72 pregnant rats were randomly divided into four groups: normal group (N), embryo implantation failure group (M), acupuncture treatment group (A), and progestin treatment group (W). Then the rats in each group were equally randomized into a day-6 (D6) group, a day-8 (D8) group, and a day-10 (D10) group. The rats in group M, group A, and group W were treated with mifepristone-sesame oil solution on day 1, while the rats in group N were injected with the same amount of sesame oil. Meanwhile, "Housanli" and "Sanyinjiao" were selected for acupuncture. From day 1 to the time of death, the rats in group A were fastened up and then acupuncture was administered while the rats in group N and group M were only fixed, and the rats in group W were given progestin. The number of implanted embryos was calculated. The expression of CXCR1 and CXCR2 in rat endometrium was detected by immunohistochemistry, Western blotting and real-time PCR. Compared to group N, the average number of implanted embryos, the protein and mRNA expression of CXCR1 (D6, D8 and D10), and the protein and mRNA expression of CXCR2 (D8 and D10) in rat endometrium were significantly decreased in group M. Compared to group M, there was significant elevation in the average number of implanted embryos, the protein expression (D6, D8 and D10) and mRNA expression (D8) of CXCR1 in rat endometrium of group A, and the protein expression (D8 and D10) and mRNA expression (D8) of CXCR2 in rat endometrium of group W. These findings indicated that acupuncture can increase the number of implanted embryos in rats of embryo implantation failure, which may be relevant with up-regulation the expression of CXCR1 and CXCR2 at maternal-fetal interface of rats with embryo implantation failure.

Problem Acupuncture has a positive effect on implantation obstacle, but the mechanism is still not clear, so the aim of the experiment is to explore the possible role that acupuncture plays in implantation. Method of study Early pregnant rats were randomized into normal group (N), group treated with mifepristone (M), acupuncture treatment group (A), and progestin treatment group (P). The model of blastocyst implantation obstacle in groups M, A, and P was established with mifepristone. Bilateral ‘Housanli’ and ‘Sanyinjiao’ were needled in group A. The expression of interleukin (IL)-12, leukemia inhibitory factor (LIF), LIFR protein, and mRNA in endometrium were detected. Results Positivity of the protein expression of IL-12, LIF, and LIFR in the endometrium was significantly higher in groups N, A, and P; positivity of the mRNA of IL-12 and LIF in the endometrium was significantly higher in groups N, A, and P. Conclusion Acupuncture could improve the poor receptive state of endometrium by promoting LIF and IL-12 secretion to improve blastocyst implantation.

In order to explore the effect of Yaoliuan capsule in the prevention and treatment of vaginal bleeding after drug-induced abortion and menses recovery after drug-induced abortion, 323 cases of gestation period < or = 49 days and without contraindication, were divided randomly into study group (168 cases, taking Yaoliuan capsule) and control group (155 cases, taking placebo capsule). The results showed that in the study group, there were 161 cases (95.8%) of complete abortion, 7 cases (4.2%) of incomplete abortion; In the control group, there were 146 cases (94.2%) of complete abortion, 6 cases (3.9%) of incomplete abortion, 3 cases (1.9%) of abortion failure. The vaginal bleeding time was 5-25 days (mean 10.8 days) in study group, while that was 6-62 days (mean 19.1 days) in control group. The menstrual cycle was 30.5+/-5. 2 days and 33.8 d+/-8.6 days respectively in study and control groups. The menstrual period was 6.1+/-3. 5 days and 9.9+/-5.1 days respectively in study and control groups. Yaoliuan capsule is an effective drug to prevent and treat vaginal bleeding following drug-induced abortion, promote menstruation recovery and prevent pelvic infection.

The clinical effects of acupuncture on idiopathic male infertility in sperm parameter and on therapeutic results in assisted reproductive technology were investigated. 22 patients failed in intracytoplasmic sperm injection (ICSI) with idiopathic male infertility were treated with acupuncture twice weekly for 8 weeks, followed by ICSI treatment again. The sperm concentration, motility, morphology, fertilization rates and embryo quality were observed. Quick sperm motility after acupuncture (18.3% +/- 9.6%) was significantly improved as compared with that before treatment (11.0% +/- 7.5%, P0.01). The normal sperm ratio was increased after acupuncture (21.1% +/- 10.4% vs 16.2% +/- 8.2%, P0.05). The fertilization rates after acupuncture (66.2%) were obviously higher than that before treatment (40.2%, P0.01). There was no significant difference in sperm concentration and general sperm motility between before and after acupuncture. The embryo quality after acupuncture was improved, but the difference between them was not significant (P0.05). Acupuncture can improve sperm quality and fertilization rates in assisted reproductive technology.

To investigate the effect of reinforcing kidney, replenishing Qi and blood activating prescription (RKRQBAP) on extracellular signal regulating kinase-1 (ERK-1) and mitogen activated protein kinase phosphatase-1 (MKP-1) of fetal rats with fetal growth restriction (FGR).Passive smoking was used to establish animal model of FGR. All pregnant rats were divided into four groups: FGR group, L-arg group: rats with FGR treated with L-arginine, Chinese medicine group (CHM group): rats with FGR treated by traditional Chinese medicine and normal control group. The expression of ERK-1 and MKP-1 in brain and liver were measured by western-blot.(1) According to FGR group, L-arg group, CHM group and normal group, the expression of ERK-1 in brain was 7.63 +/- 0.22, 10.03 +/- 0.41, 11.03 +/- 0.30, 11.44 +/- 0.09 and MKP-1 was 7.41 +/- 0.38, 10.35 +/- 0.60, 10.60 +/- 0.14, 11.60 +/- 0.62. (2) The expression of ERK-1 in liver was 4.73 +/- 0.54, 5.83 +/- 0.17, 11.37 +/- 0.12, 12.34 +/- 0.14 accordingly and MKP-1 was 9.07 +/- 0.61, 10.66 +/- 0.08, 14.27 +/- 0.73, 14.92 +/- 0.17. (3) The expression of ERK-1 and MKP-1 in brain and liver was much lower in FGR group than in normal group (P0.01), and that of CHM group was much higher than in FGR group (P0.01) and closed to normal group (P0.05). The expression of ERK-1 in brain was much higher in CHM group than in L-arg group (P0.05), the expression of MKP-1 was almost the same (P0.05); Both of them in liver were higher in CHM group than in L-arg group (P0.01).The possible mechanism which the RKRQBAP cure FGR is to affect the expression of ERK-1 and MKP-1 and to promote growth- related genes expression and restrain apoptosis. In addition, RKRQBAP is superior to L-arginine in treatment of FGR.