Effect of Acupuncture on Endometrial Blood Flow in Women Undergoing in vitro Fertilization Embryo Transfer: A Single Blind, Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional (3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer (IVF-ET). METHODS: Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days (from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji (CV3), Qihai (CV 6), Sanyinjiao (SP6), Taichong (LR 3), Tianshu (ST 25), Guilai (ST 29) and Zusanli (ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index (VI), flow index (FI) and vascularization flow index (VFI), endometrial thickness and volume, subendometrial VI (sVI), subendometrial FI (sFI), subendometrial VFI (sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births. RESULTS: Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group (P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births (P>0.05). CONCLUSIONS: Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parameters VI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity. (Registration No. ChiCTR2100053354).

Effect of acupuncture on the opening time of implantation window and endometrial receptivity in controlled ovarian hyperstimulation rats during peri-implantation period.

Purpose: To investigate the effect of acupuncture for improving the pregnancy rate of COH rats from the viewpoint of regulating the opening time of the implantation window and endometrial receptivity. Methods: Experimental rats were randomly divided into normal group (N), model group (M) and acupuncture group(A), and samples were collected on Day 4, 5 and 6 after mating. COH rats were treated with acupuncture at SP6, LR3, and ST36 once a day for 7 times. The pinopodes were observed under a scanning electron microscope. Serum estrogen and progesterone levels were measured via ELISA. The protein and mRNA levels of estrogen receptor (ER), progesterone receptor (PR), leukemia inhibitory factor (LIF), integrin ß3, vascular endothelial growth factor (VEGF), and fibroblast growth factor 2 (FGF-2) in the endometrium were evaluated via West-blot, immunohistochemistry, and PCR. Results: Compared with group N, the pregnancy rate of group M was significantly decreased (P<0.05), and the abnormal serum hormone levels and implantation window advancement were observed. Compared with group M, the pregnancy rate of group A was significantly increased (P<0.05), the supraphysiological serum progesterone levels were restored to normalcy (P<0.05), and the advanced implantation window was restored to a certain extent. Further, the abnormal ER, PR, LIF, integrin ß3, VEGF, and FGF-2 expression levels of the endometrium got recovered to varying degrees. Conclusion: Acupuncture may restore the estrogen and progesterone balance in COH rats and the forward shift of the implantation window to a certain extent, improving the endometrial receptivity and finally improving the pregnancy rate of COH rats.

Faecalibacterium prausnitzii Improves Lipid Metabolism Disorder and Insulin Resistance in Type 2 Diabetic Mice.

Purpose: Additional effective therapeutic strategies for Type 2 diabetes (T2D) patients are urgently needed. Gut microbiota plays an important role in T2D development and is a promising treatment strategy for T2D patients. Faecalibacterium prausnitzii (F. prausnitzii) is regarded as one of the most important bacterial indicators for a healthy gut, but the mechanisms of its anti-diabetic properties are still unclear. Methods and Results: The abundance of F. prausnitzii in feces of patients with T2D was detected by using qPCR. The effects of F. prausnitzii on glucose homeostasis, insulin resistance (IR), dyslipidemia, hepatic steatosis and inflammation were investigated in type 2 diabetic (T2D) db/db mice. We also investigated F. prausnitzii in people. Our results showed that the abundance of F. prausnitzii was significantly lower in T2D patients compared to healthy subjects. In T2D mice, we found that F. prausnitzii treatment significantly decreased fasting blood glucose and IR index, indicating improved glucose intolerance as well as IR. Furthermore, based on evaluation of lipid-regulating enzyme activities and proinflammatory cytokine levels, F. prausnitzii was not only able to improve inflammation in both adipose tissue and liver, but also ameliorate hepatic steatosis through inhibiting the activity of hepatic lipogenic enzymes. Conclusion: These results suggested that F. prausnitzii might serve as a therapeutic option for T2D by improved IR, lipid metabolism and inflammation.

The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro.

OBJECTIVE: JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis. METHODS: HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 µmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay. RESULTS: HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1ß (P < 0.001), and IL-18 levels (P < 0.001). CONCLUSION: JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.

Integrating network pharmacology and experimental validation to decipher the mechanism of the Chinese herbal prescription JieZe-1 in protecting against HSV-2 infection.

CONTEXT: The Chinese herbal prescription JieZe-1 (JZ-1) is effective against HSV-2 (Herpes simplex virus type 2) infection. However, its mechanism remains unclear. OBJECTIVE: To explore the mechanism of JZ-1 in protecting against HSV-2 infection. MATERIALS AND METHODS: Using the methods of network pharmacology, the hub components and targets were screened and functionally enriched. We established a genital herpes (GH) mouse model and observe the disease characteristics. Then, the GH mice in different groups (10 per/group) were treated with 20 µL JZ-1 gel (2.5, 1.5, and 0.5 g/mL), acyclovir gel (0.03 g/mL), or plain carbomer gel twice a day. The symptom score, vulvar histomorphology, and virus load were measured. The critical proteins of caspase-1-dependent pyroptosis were analysed by microscopy, co-immunoprecipitation, western blotting, and ELISA. Molecular docking was also performed. RESULTS: Network pharmacology analysis identified 388 JZ-1 targets related to HSV-2 infection, with 36 hub targets and 21 hub components screened. The TCID50 of HSV-2 was 1 × 10-7/0.1 mL. JZ-1 gel (2.5 g/mL) can effectively reduce the symptom score (81.23%), viral load (98.42%) and histopathological changes, and significantly inhibit the proteins expression of caspase-1-dependent pyroptosis in GH mice (p< 0.05). The molecular docking test showed a good binding potency between 11 components and caspase-1 or interleukin (IL)-1ß. DISCUSSION AND CONCLUSIONS: The present study demonstrated that JZ-1 protected mice from HSV-2 infection and inhibit the caspase-1-dependent pyroptosis in GH mice. It is of significance for the second development of JZ-1 and the exploration of new drugs.

The Effect of Electroacupuncture Treatment with Different Intensities for Functional Diarrhea: A Randomized Controlled Trial.

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.

Electroacupuncture for the treatment of perimenopausal syndrome: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the efficacy, comparative effectiveness and safety of electroacupuncture (EA) in the treatment of perimenopausal syndrome (PMS). METHODS: Nine databases were searched until June 2019. Only relevant randomized controlled trials (RCTs) of EA for PMS were included. RESULTS: Twelve trials involving 746 women were included. EA and hormone therapy (HT) did not significantly differ in terms of effective rate (risk ratio (RR) = 0.98, 95% confidence interval (CI) = 0.93 to 1.04), Kupperman index (KI) (mean difference (MD) = -0.25, 95% CI = -0.76 to 0.26) and serum levels of follicle-stimulating hormone (FSH) (MD = -3.80, 95% CI = -11.59 to 3.98) or luteinizing hormone (LH) (MD = -2.51, 95% CI = -10.72 to 5.70). Serum estradiol (E2) levels were significantly lower in EA versus HT groups (MD = -60.58, 95% CI = -71.93 to -49.23). Compared with sham EA, EA had a significantly greater effect on reductions in KI (MD = -4.71, 95% CI = -6.57 to -2.86) and hot flushes score/24 h (MD = -2.43, 95% CI = -2.93 to -1.93). There were no significant differences between EA and manual acupuncture (MA) in terms of effective rate (RR = 1.14, 95% CI = 0.98 to 1.33) or serum FSH (MD = -2.87, 95% CI = -29.65 to 23.91), LH (MD = 2.73, 95% CI = -9.65 to 15.11) or E2 (MD = 26.80, 95% CI = -12.06 to 65.65). However, it seemed that EA had a better effect than MA on KI (MD = -2.44, 95% CI = -4.80 to -0.08). Subgroup analyses indicated that EA may have more of a benefit in the pre-menopausal state (hot flushes score/24 h: MD = -1.66, 95% CI = -3.49 to 0.17) compared to post-menopause (p > 0.05). CONCLUSION: The effect of EA appeared broadly similar to HT and MA in the treatment of PMS, although EA-associated reductions in KI were superior to MA and sham EA, suggesting effects beyond placebo. The evidence base is limited by a small number of eligible studies, risk of bias and clinical/statistical heterogeneity, limiting our ability to draw firm conclusions. As such, additional larger scale, high-quality RCTs are needed.

JieZe-1 Alleviates HSV-2 Infection-Induced Genital Herpes in Balb/c Mice by Inhibiting Cell Apoptosis via Inducing Autophagy.

Objectives: Genital herpes (GH) is a common sexually transmitted disease mainly caused by herpes simplex virus 2 (HSV-2). JieZe-1 (JZ-1) is an in-hospital prescription that has been used in Tongji Hospital for many years to treat various lower female genital tract infectious diseases. Our previous study showed that JZ-1 can protect against HSV-2 infection in vitro by inducing autophagy. However, whether JZ-1 can protect against HSV-2 infection in vivo, and the underlying mechanisms involved still remain unclear. Therefore, this study was designed to address above questions. Methods: 8-week-old female balb/c mice were injected intravaginally with HSV-2 to establish GH model. The symptom score, body weight, and histological examination were recorded to assess the animal model of HSV-2 infected and the therapeutic effect of JZ-1. Inflammatory response was determined by detecting inflammatory cells infiltration and local cytokines levels. After then, under autophagy inhibitor chloroquine application, we measured the levels of cell apoptosis and autophagy and investigated the relationship between enhanced autophagy and cell apoptosis. Next, the classic PI3K/Akt/mTOR axis was examined, and in vitro experiment was carried out for further verification. Results: Our results showed that JZ-1 administration significantly reduces symptom score, increases weight gain and alleviates histological damage in HSV-2 infection-induced GH in balb/c mice. JZ-1 administration obviously ameliorates inflammatory responses with reduced T-lymphocytes, T helper cells, macrophages and neutrophils infiltration, and local IL-1ß, IL-6, TNF-α and CCL2 levels. HSV-2 infection leads to massive cell apoptosis, which was also restored by JZ-1. Meanwhile, we found that HSV-2 infection blocks autophagic flux in vivo and JZ-1 administration induces autophagy. After chloroquine application, it was observed that the inhibition of autophagy is strongly associated with increased cell apoptosis, whereas the promotion of autophagy remarkedly decreases apoptosis. These results suggested that JZ-1 inhibits cell apoptosis in GH by inducing autophagy, which was further supported in later in vitro experiment. Additionally, PI3K/Akt/mTOR signaling pathway was also downregulated by JZ-1 administration. Conclusion: Our data demonstrated that JZ-1 can alleviate HSV-2 infection-induced GH in balb/c mice by inhibiting cell apoptosis via inducing autophagy, and the underlying mechanisms may be associated with the inhibition of PI3K/Akt/mTOR pathway.

The Chinese Herbal Prescription JieZe-1 Inhibits Membrane Fusion and the Toll-like Receptor Signaling Pathway in a Genital Herpes Mouse Model.

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).

Investigation on the mental health status of pregnant women in China during the Pandemic of COVID-19.

PURPOSE: To evaluate the anxiety and depression in pregnant women in China, and its influencing factors during the corona virus disease 2019 (COVID-19) pandemic. METHODS: From February 22 to February 27, a questionnaire survey was conducted on 156 pregnant women, including demographic characteristics, a self-rating anxiety scale (SAS), and a self-depression rating scale (SDS). RESULTS: A total of 13 non-homologous end-joining (8.3%, 13/156) patients were anxious, 79 patients (50.6%, 79/156) were depressed, and 13 patients (8.3%, 13/156) suffered from both anxiety and depression. The SAS score of pregnant women was 40.55 ± 6.09, and the SDS score was 50.42 ± 11.64. For the SAS score, only 8.3% of all patients (13/156) were in a light anxiety state. For the SDS score, 46.79% (73/156) of patients was normal, 23.72% of patients (37/156) showed mild depression, 22.44% (35/156) showed moderate depression, and 4.49% (7/156) showed severe depression. No significant changes were observed in SAS and SDS scores between patients from different regions within China, health state, gestational week, educational background, and living condition (P > 0.05). Moreover, no significant differences were observed between diagnosed/suspected patients and the normal control group (P > 0.05), and between pregnant women in Wuhan compared to other regions (P > 0.05). CONCLUSION: During the COVID-19 epidemic, the anxiety level of pregnant women was the same as that before the epidemic, while the level of depression was significantly higher. Pregnant women who lived in Wuhan, the epicenter of the epidemic, were not more anxious or depressed compared to pregnant women in other regions during the COVID-19 epidemic. Furthermore, the mental health status of pregnant women with COVID-19 was not more severe.

General Issues in Clinical Research of Acupuncture and In Vitro Fertilization.

In vitro fertilization-embryo transfer (IVF-ET), a well-developed technology, provides the last possibility or hope for infertile women. However, the live birth rate per IVF cycle is still not satisfactory. Acupuncture is a frequently used adjunctive therapy drawing wide attention on improvement of IVF. Although so many randomized controlled trials have been evaluating the effect of acupuncture on IVF in the past 20 years, the exact efficacy of acupuncture on IVF is still controversy mainly because of no consensus on placebo control and acupuncture scheme. This paper focused on the general issues in clinical research of acupuncture and IVF and gave some suggestions for future directions.

Efficacy of Electro-acupuncture in Treatment of Functional Constipation: A Randomized Controlled Trial.

Functional constipation (FC) is a chronic disease that significantly affects the life quality of patients. Acupuncture has been used for the treatment of FC for many years, but its effectiveness has not been scientifically assessed. The present study aimed to evaluate the efficacy of electro-acupuncture (EA) in relieving the symptoms, mental states and quality of life (QOL) of FC patients. A total of 96 FC patients were randomly allocated into EA, mosapride & sham EA group (MS) and mosapride control group (MC). In the EA group, patients were treated with 16 sessions of needling at Quchi (LI11) and Shangjuxu (ST37) bilaterally, 5 times a week in the first 2 weeks, and 3 times a week in the last 2 weeks. In the MC group, patients were treated with 5 mg mosapride citrate three times a day for 4 weeks. In the MS group, patients underwent sham EA and the same mosapride citrate treatment as in the MC group. The primary outcome was the number of weekly spontaneous bowel movements (SBMs). The secondary outcomes included stool consistency, intensity of defecating difficulty, 36-Item Short-Form Health Survey (SF-36), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and the validated Patient Assessment of Constipation-Quality of Life (PAC-QOL). The results showed that as compared with the baseline, EA significantly improved the weekly SBMs, stool consistency and intensity of defecating difficulty (P<0.05). It also partly ameliorated the PAC-QOL, SF-36, SDS and SAS scores when compared with MC or MS group (P<0.05). However, no significant difference was observed between MS and MC groups in bowel function outcomes and QOL scores. It was concluded that EA could effectively improve bowel function, mental states and QOL of FC patients.

Manual acupuncture versus sham acupuncture and usual care for prophylaxis of episodic migraine without aura: multicentre, randomised clinical trial.

OBJECTIVE: To assess the efficacy of manual acupuncture as prophylactic treatment for acupuncture naive patients with episodic migraine without aura. DESIGN: Multicentre, randomised, controlled clinical trial with blinded participants, outcome assessment, and statistician. SETTING: Seven hospitals in China, 5 June 2016 to 15 November 2018. PARTICIPANTS: 150 acupuncture naive patients with episodic migraine without aura. INTERVENTIONS: 20 sessions of manual acupuncture at true acupuncture points plus usual care, 20 sessions of non-penetrating sham acupuncture at heterosegmental non-acupuncture points plus usual care, or usual care alone over 8 weeks. MAIN OUTCOME MEASURES: Change in migraine days and migraine attacks per four weeks during weeks 1-20 after randomisation compared with baseline (four weeks before randomisation). RESULTS: Among 150 randomised patients (mean age 36.5 (SD 11.4) years; 123 (82%) women), 147 were included in the full analysis set. Compared with sham acupuncture, manual acupuncture resulted in a significantly greater reduction in migraine days at weeks 13 to 20 and a significantly greater reduction in migraine attacks at weeks 17 to 20. The reduction in mean number of migraine days was 3.5 (SD 2.5) for manual versus 2.4 (3.4) for sham (adjusted difference -1.4, 95% confidence interval -2.4 to -0.3; P=0.005) at weeks 13 to 16 and 3.9 (3.0) for manual versus 2.2 (3.2) for sham (adjusted difference -2.1, -2.9 to -1.2; P<0.001) at weeks 17 to 20. At weeks 17 to 20, the reduction in mean number of attacks was 2.3 (1.7) for manual versus 1.6 (2.5) for sham (adjusted difference -1.0, -1.5 to -0.5; P<0.001). No severe adverse events were reported. No significant difference was seen in the proportion of patients perceiving needle penetration between manual acupuncture and sham acupuncture (79% v 75%; P=0.891). CONCLUSIONS: Twenty sessions of manual acupuncture was superior to sham acupuncture and usual care for the prophylaxis of episodic migraine without aura. These results support the use of manual acupuncture in patients who are reluctant to use prophylactic drugs or when prophylactic drugs are ineffective, and it should be considered in future guidelines. TRIAL REGISTRATION: Clinicaltrials.gov NCT02765581.

The Chinese herbal prescription JZ-1 induces autophagy to protect against herpes simplex Virus-2 in human vaginal epithelial cells by inhibiting the PI3K/Akt/mTOR pathway.

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-ß 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.

Phillyrin protects mice from traumatic brain injury by inhibiting the inflammation of microglia via PPARγ signaling pathway.

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.

Acupuncture for chronic fatigue syndrome: a systematic review and meta-analysis.

OBJECTIVE: To evaluate evidence for the efficacy of acupuncture for chronic fatigue syndrome (CFS). METHODS: Randomized controlled trials (RCTs) comparing acupuncture with sham acupuncture, other interventions that may have a therapeutic effect, or no intervention, for the treatment of CFS, were searched for in the following databases up to March 2018: Pubmed; Embase; the Cochrane Library; Web of Science; Wanfang database; China National Knowledge Infrastructure (CNKI); Chinese Biomedicine (CBM) database; and VIP database. Risk of bias was determined using the Cochrane tool. Meta-analyses were performed using RevMan V.5.3 software. The GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) was adopted for levels of evidence. RESULTS: Sixteen studies with 1346 subjects were included. Most studies had low methodological quality. Meta-analyses showed a favourable effect of acupuncture on overall response rate compared with sham acupuncture (four studies, 281 participants, RR=2.08, 95% CI 1.4 to 3.1, I2=64%, low certainty) and Chinese herbal medicine (three studies, 290 participants, RR=1.17, 95% CI 1.07 to 1.29, I2=0%, low certainty). Acupuncture also appeared to significantly reduce fatigue severity measured by Chalder's Fatigue Scale and the Fatigue Severity Scale compared with other types of control. CONCLUSION: Our review indicated that acupuncture was more effective than sham acupuncture and other interventions (Chinese herbal medicine, mainly), but no firm conclusion could be reached owing to limited data, poor quality and potentially exaggerated effect size evaluation. Further large, rigorously designed and reported RCTs are required.

Electroacupuncture facilitates implantation by enhancing endometrial angiogenesis in a rat model of ovarian hyperstimulation.

Controlled ovarian hyperstimulation (COH) impairs the synchronized development of endometrium and embryo, resulting in the failure of embryo implantation. Here, we investigated what effects electroacupuncture had on embryo implantation in COH rats. Female rats were randomly assigned to four groups: normal (N), model (M), electroacupuncture (EA), and electroacupuncture pretreatment (PEA). Rats in groups M, EA, PEA were injected with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin to establish the COH model. Rats in group EA received electroacupuncture treatment from the PMSG injection day to the 3rd day of pregnancy (D3), while those in group PEA received electroacupuncture treatment for 3 days before the PMSG day and continuing to D3. Furthermore, another 30 female rats who received the same treatment as the rats in group PEA were injected with siVEGFR2 into uterine lumen. The endometrial microvascular density (MVD) and the expression levels of vascular endothelial growth factor-A, angiopoietin-1, and fibroblast growth factor-2 were significantly lower in groups M than in groups N and PEA. The percentage of dolichos biflorus agglutinin positive uterine natural killer cells in groups N, EA and PEA was higher than that in group M. After the siVEGFR2 injection, the protein expression levels of vascular endothelial growth factor receptor 2 (VEGFR2), PI3K, p-AKT and p-ERK, the embryo number and the MVD were significantly reduced. In conclusion, electroacupuncture can facilitate embryo implantation in COH rats by activating the VEGFR2/PI3K/AKT and VEGFR2/ERK signaling pathways which have a positive relationship with endometrial angiogenesis.

[Progress of fMRI Research on "Deqi" of Acupuncture and Our Considerations About Further Studies].

The objectification of "Deqi" of acupuncture is a hot topic in acupuncture research at present, and functional magnetic resonance imaging (fMRI) is one of the most frequently-used techniques for revealing its brain responses. We searched literature about "Deqi" from PubMed in recent 10 years by using key words "Deqi""acupuncture sensation""needling sensation" and fMRI, trying to expound the central mechanism of "Deqi" and to put forward our understandings. Acupuncture "Deqi" evoked deactivation of the limbic-paralimbic-neocortical network (LPNN)/ default mode network (DMN), including medial prefrontal cortex (frontal pole, anterior cingulate), temporal lobe (amygdala, hippocampus, parahippocampus gyrus, temporal pole), and apparent activation of brain regions as the somatosensory cortex, thalamic-somatosensory area-insular lobe, orbitofrontal cortex, etc., which may enhance the connectivity of brain networks and function in analgesia, anti-anxiety, anti-depression, etc., but the activated and deactivated brain regions are different from study to study possibly due to the stimulated different acupoints, subjects' psychophysical conditions, scanning parameters, image acquiring sequences, etc. It is recommended that the coming stu-dies should pay more attention to the influence of acupuncture "Deqi" on brain functions in subjects suffering from diseases, the brain response characteristics of the longer post-effects and the accumulated effects of acupuncture treatment.

Effect of Acupuncture on Endometrial Angiogenesis and Uterus Dendritic Cells in COH Rats during Peri-Implantation Period.

This study was to explore the mechanism of acupuncture on regulating the endometrial angiogenesis and uterus dendritic cells (uDCs) during the peri-implantation period. Rats, in early pregnancy, were randomized into five groups: normal (N), model (M), acupuncture (A), progesterone (P), and A + P groups. The COH model was established using pregnant mare serum, combined with human chorionic gonadotrophin. Endometrium was collected on days 4, 6, and 8 (D4, D6, and D8) of gestation. Compared with group M, both VEGF and FGF-2 protein and mRNA levels were significantly lower on D4 and higher on D6 and D8 (P < 0.05), except for VEGF of group P on D8; the proportion of uterus dendritic cells (uDCs) in the endometrium was significantly lower on D4 and D6 and higher on D8 (P < 0.05). In vitro, except for the proliferation of group P on D8, proliferation, tube formation, and migration of uDCs were significantly decreased on D4 and increased on D8 (P < 0.05). In addition, acupuncture or progesterone regulated the secretion levels of VEGF, IL-15, and IL-18 secreted by uDCs instead of soluble sFLT-1. In conclusion, acupuncture may regulate angiogenesis of the endometrium and the number and roles of uDCs after COH, and the specific mechanism may be different with progesterone.

Electroacupuncture for Functional Constipation: A Multicenter, Randomized, Control Trial.

Background and Aim. To investigate the efficacy and safety of electroacupuncture (EA) with different current intensities for functional constipation (FC) and to assess whether the effects of EA with different current intensities are superior to the mosapride. Methods. Patients with FC were randomly divided into low current intensity group (LCI), high current intensity group (HCI), and mosapride group (MC). The primary outcome was three or more spontaneous bowel movements (SBMs) per week and an increase of one or more SBMs from baseline during at least 3 of the 4 weeks. Results. The primary outcome was reached by 53.45%, 66.15%, and 52.24% of the patients who received LCI, HCI, and mosapride, respectively. EA can significantly improve the weekly SBMs and stool consistency and reduce straining severity (p < 0.0001, all). HCI improved the quality of life better than mosapride (p < 0.05) and reduced the proportion of severe constipation more than LCI and mosapride (p < 0.05, both). Conclusions. EA is effective and safe at both current intensities for FC; therapeutic effects of LCI and HCI are not superior to mosapride. EA is superior to mosapride in improving patients' life quality and satisfaction level of treatment; EA has fewer adverse events than mosapride.