In recent years, concerns about the adverse effects of hormone replacement therapy have increased interest in alternative therapies for the management of the symptoms of perimenopause. Here, we investigated the effects of moxibustion, a traditional Chinese practice that is involved in heated Artemisia vulgaris (mugwort) stimulation, on hormonal imbalance and ovarian granulosa cell (GC) apoptosis in a rat model of perimenopause. Our results showed that mild warm moxibustion (MWM) modulated the circulating levels of estradiol and follicle-stimulating hormone and their receptors and inhibited apoptosis in the ovaries of perimenopausal rats, similar to the effect of estrogen. Further investigation revealed that the effects of MWM on ovary tissues and cultured GCs were mediated by the modulation of the activity of Forkhead box protein O1 and involved the JAK2/STAT3 pathway. Our results provide information on the factors and pathways modulated by MWM and shed light on the mechanism underlying the beneficial effect of moxibustion on the symptoms of perimenopause.

The aim is to explore the effect of acupuncture on Th1, Th2 cytokines in rats of implantation failure. Early pregnant rats were randomized into normal group (N), implantation failure group (M), acupuncture group (A), progestin group (H). The model was established with mifepristone. Samples of serum, endometrium were collected on Day 5, 6 and 8 of pregnancy. Compared with group M, the number of embryos was significantly higher in groups N, A and H; IL-1β, IL-2 protein in serum and endometrium were significantly lower in groups N, A and H, while IL-4, IL-10 were significantly higher in groups N, A and H; the endometrial IL-2, IL-4 mRNA were significantly lower in groups N, A and H, while IL-1β, IL-10 mRNA were significantly higher in groups N, A and H. Acupuncture could improve the poor receptive state of endometrium due to mifepristone by promoting Th2 cytokines secretion and inhibiting Th1 cytokines to improve blastocyst implantation.

Previous studies have demonstrated that acupuncture is beneficial to patients with Crohn's disease (CD), but the mechanism underlying its therapeutic effects remains unclear. To identify the mechanism by which acupuncture treats CD, the balance between Th17 and Treg cells was assessed in CD patients. In this study, Ninety-two CD patients were randomly and equally assigned to a treatment group that were treated with herb-partitioned moxibustion and acupuncture or a control group with wheat bran-partitioned moxibustion and superficial acupuncture. The effect of these treatments on Th17 and Treg cells and their related molecular markers in the intestinal mucosa were detected before (week 0) and after (week 12) treatment. The results suggested that the ratio of Th17 and Treg cells was significantly decreased after treatment and that the levels of IL-17 and RORγt in the intestinal mucosa were obviously reduced, while the expression of FOXP3 was increased after treatment in both groups. In the treatment group, the expression of these molecules was more markedly regulated than the control group. In conclusion, moxibustion and acupuncture have been shown to regulate the ratio of Th17 and Treg cells in the intestinal mucosa of CD patients and restore the balance between these immune cell subsets.

Background. This study compared outcomes of abdominal lifting and compression cardiopulmonary resuscitation (ALP-CPR) with standard CPR (STD-CPR). Materials and Methods. Patients with cardiac arrest seen from April to December 2014 were randomized to receive standard CPR or ALP-CPR performed with a novel abdominal lifting/compression device. The primary outcome was return of spontaneous circulation (ROSC). Results. Patients were randomized to receive ALP-CPR (n = 40) and STD-CPR (n = 43), and the groups had similar baseline characteristics. After CPR, 9 (22.5%) and 7 (16.3%) patients in the ALP-CPR and STD-CPR groups, respectively, obtained ROSC. At 60 minutes after ROSC, 7 (77.8%) and 2 (28.6%) patients, respectively, in the ALP-CPR and STD-CPR groups survived (P = 0.049). Patients in the ALP-CPR group had a significantly higher heart rate and lower mean arterial pressure (MAP) than those in the STD-CPR group (heart rate: 106.8 versus 79.0, P < 0.001; MAP: 60.0 versus 67.3 mm Hg, P = 0.003). The posttreatment PCO2 was significantly lower in ALP-CPR group than in STD-CPR group (52.33 versus 58.81, P = 0.009). PO2 was significantly increased after ALP-CPR (45.15 to 60.68, P < 0.001), but it was not changed after STD-CPR. PO2 after CPR was significantly higher in the ALP-CPR group (60.68 versus 44.47, P < 0.001). There were no differences between genders and for patients who are > 65 or ≤ 65 years of age. Conclusions. The abdominal lifting and compression cardiopulmonary resuscitation device used in this study is associated with a higher survival rate after ROSC than standard CPR.

Background. Aidi injection is an important adjuvant anticancer drug commonly used in China. Can Aidi injection plus docetaxel-based chemotherapy improve clinical efficacy with good safety in NSCLC? To further reveal its clinical effectiveness, we systematically evaluated all the related studies. Method. We collected all the studies about Aidi injection plus docetaxel-based chemotherapy for NSCLC on Medline, Embase, Web of Science, CNKI, VIP, Wanfang, CBM, CENTRAL, Chi-CTR, and US-clinical trials. We evaluated their methodological bias risk according to the Cochrane evaluation handbook (5.1.0), extracted data following the predesigned data extraction form according to the PICO principle, and synthesized the data using meta-analysis. Results. We included 36 RCTs with 2837 patients, and most studies had unclear bias risk. The merged RR values and their 95% CI of meta-analysis for ORR, DCR, and QOL were as follows: 1.30 (1.19, 1.42), 1.17, (1.12, 1.22), and 1.73 (1.54, 1.95). The merged RR values for neutropenia, thrombocytopenia, anemia, gastrointestinal toxicity, hepatorenal dysfunctions, and alopecia were as follows: 0.70 (0.61, 0.79), 0.63 (0.53, 0.75), 0.60 (0.48, 0.75), 0.76 (0.65, 0.89), 0.56 (0.36, 0.88), and 0.58 (0.36, 0.93). Compared with chemotherapy alone, all differences were statistically significant. Subgroup analysis showed that, with 100 ml, 80-100 ml, and 50 ml, Aidi injection could increase the tumor response and Aidi injection plus DP, DC, and DO could increase the tumor response. Meta-analysis results had good stability. Conclusions. Aidi injection plus docetaxel-based chemotherapy, especially plus DP, DC, and DO, may significantly improve the clinical efficacy and QOL in NSCLC. It may also have low risk of hematotoxicity, gastrointestinal toxicity, and low risk of inducing hepatorenal dysfunctions. Aidi injection may have attenuation and synergistic efficacy to docetaxel chemotherapy. All these need to have new evidence to be proved.

Bufalin has been shown to induce cancer cell death through apoptotic pathways. However, the molecular mechanisms are not well understood. In this study, we used the confocal fluorescence microscopy (CFM) to monitor the spatio-temporal dynamics of reactive oxygen species (ROS) production, Bax translocation and caspase-3 activation during bufalin-induced apoptosis in living human lung adenocarcinoma (ASTC-a-1) cells. Bufalin induced ROS production and apoptotic cell death, demonstrated by Hoechst 33258 staining as well as flow cytometry analysis. Bax redistributed from cytosol to mitochondria from 12 to 48 h after bufalin treatment in living cells expressed with green fluorescent protein Bax. Treatment with the antioxidant N-acetyl-cysteine (NAC), a ROS scavenger, inhibited ROS generation and Bax translocation and led to a significant protection against bufalin-induced apoptosis. Our results also revealed that bufalin induced a prominent increase of caspase-3 activation blocked potently by NAC. Taken together, bufalin induced ROS-mediated Bax translocation, mitochondrial permeability transition and caspase-3 activation, implying that bufalin induced apoptosis via ROS-dependent mitochondrial death pathway in ASTC-a-1 cells.

Background. Although the effectiveness of acupuncture therapy on functional dyspepsia (FD) has been systematically reviewed, the available reports are still contradictive and no robust evidence has been provided to date. Objective. To assess the current evidence of high quality on the effects of acupuncture for patients with FD. Methods. A comprehensive literature database search was conducted to identify randomized controlled trials (RCTs) comparing acupuncture therapies (including manual acupuncture and electroacupuncture) to sham acupuncture and medication use. A meta-analysis was performed following a strict methodology. Results. 16 RCTs involving 1436 participants were included. The majority of the trials were determined to be of low quality. Positive results were found for acupuncture in improving the Nepean Dyspepsia Index (NDI) and scores of the MOS 36-Item Short-Form Health Survey (SF-36), as well as in alleviating relevant symptoms (especially postprandial fullness and early satiation) of FD patients. Conclusion. Based on current available evidence, acupuncture therapy achieves statistically significant effect for FD in comparison with sham acupuncture and is superior to medication (prokinetic agents) in improving the symptoms and quality of life of FD patients. Nonetheless, despite stringent methodological analyses, the conclusion of our review still needs to be strengthened by additional RCTs of higher quality.

Sinomenine (SIN) is the active ingredient of the Chinese herb Sinomenium acutum that has been used to treat rheumatoid arthritis (RA) for about 30 years in China. Marked expression of the alpha7 nicotinic acetylcholine receptor (α7nAChR) in the joint synovium of RA patients suggested a relationship between α7nAChR and RA. This study investigated the relationship between α7nAChR and RA development and the effects of SIN on α7nAChR expression in vivo and in vitro. Sprague-Dawley rats were injected with complete Freund's adjuvant to induce arthritis and then treated with SIN or methotrexate (MTX) from day 0 to day 30. Four clinical parameters-paw volume, arthritic index (AI), serum TNF-α concentration, and erythrocyte sedimentation rate (ESR)-were measured. Splenic lymphocytes were isolated for Bacille Calmette Guerin (BCG) stimulation. α7nAChR expression in tissues and cells was examined by RT-PCR, western blot, immunofluorescence, flow cytometry, and immunohistochemistry. Cell proliferation was evaluated by the CCK-8 assay. The relationship between α7nAChR expression and the four clinical parameters was analyzed by single-factor correlation analysis. Our results showed that the paw volume, AI, TNF-α concentration, and ESR in adjuvant-induced arthritic (AIA) rats were reduced by SIN or MTX treatment. SIN decreased α7nAChR expression in tissues and cells compared to the model group, while MTX had no significant effect on α7nAChR expression. Moreover, there was a positive relationship between α7nAChR expression and paw swelling, AI, and TNF-α concentration. Splenic lymphocyte activation was accompanied by increased α7nAChR expression, while SIN treatment inhibited cell activation and downregulated α7nAChR expression. α7nAChR expression showed a positive correlation with the progression of RA in AIA rats that may involve lymphocyte activation. Different from MTX, the inhibition of SIN on α7nAChR expression might contribute to its antiarthritic effect, suggesting that SIN could be an important supplement to the treatment strategy for RA.

Analysis of androgen secretion and sperm production was conducted in the testis to investigate the efficacy of moxibustion on testicular function in aging rats. Male Sprague-Dawley rats were randomly divided into the aging group (N = 8), the mild-warm moxibustion group (N = 8), and the youth control group (N = 8). Rats in the mild-warm moxibustion group (MWMG) were exposed to mild-warm moxibustion at the Zusanli (ST36) and Shenshu (BL23) acupuncture points daily, from the age of 12 months until the age of 24 months. After the intervention, testicular tissue was harvested from all rats across groups. Changes in testicular structure were examined by hematoxylin and eosin (H&E) stain. Detection of the apoptosis of spermatogenic cells was performed by the TUNEL assay. Testosterone level in the testis was analyzed by the ELISA assay, and the expression of Bax, Bcl-2, and androgen receptor (AR) in the testis was evaluated by immunohistochemistry. AR expression analysis was subsequently performed by the western blotting assay, and the detection of telomerase activity of the testis and the expression of Bax, Bcl-2, and AR mRNA were performed by real-time PCR. Compared with the youth controls, telomerase activity in the testis, testosterone levels, expression of AR, and expression of antiapoptosis factor Bcl-2 protein and mRNA were significantly decreased (P < 0.01) in the aging group. Spermatogenic cell apoptosis (P < 0.01) and proapoptotic factor Bax expression were significantly increased (P < 0.01) in the aging rats compared with the youth control group. The MWMG exhibited significant increases in testicular telomerase activity, testosterone level, AR expression, and antiapoptosis factor Bcl-2 expression (P < 0.05 or P < 0.01) compared with the aging group. In this experimental group, spermatogenic apoptosis was inhibited (P < 0.01) and proapoptotic factor Bax expression significantly reduced (P < 0.01). Mild-warm moxibustion can inhibit reproductive senescence by improving telomerase activity, improving AR expression, restoring testosterone, and inhibiting spermatogenic apoptosis via regulation of Bcl-2/Bax.

Previous studies showed that Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription, could alleviate cognitive dysfunction of Alzheimer's disease (AD) patients. However, the mechanisms remain unclear; we have now examined the effect of DSS on SAMP8 and elucidated the possible mechanism. Animals were treated with DSS for 2 months, and step-down test and Morris water maze (MWM) test were used to evaluated cognitive abilities. The estradiol (E2), NO, and glycine in blood plasma or in hippocampus were detected to explore the possible mechanisms. The latency of SAMP8 in step-down test was shorter than that of age-matched SAMR1, and DSS increased the latency especially in female animals. In MWM test, we got similar results; SAMP8 spent more time to find the platform, and DSS decreased the time before finding the platform, with little effect on swim velocity, during the training sessions. During test session, DSS increased the time spent in target quadrant especially in female SAMP8. In female SAMP8, plasma E2, NO, and glycine were elevated in plasma or hippocampus tissue. In conclusion, DSS could ameliorate deterioration of cognition in SAMP8, especially in female animals. Increasing E2, NO, and glycine might contribute to the cognitive improvement effect of DSS in female SAMP8.

Acupuncture has demonstrated the function in ameliorating depressive-like behaviors via modulating PKA/CREB signaling pathway. To further confirm the antidepressant mechanism of EA on the mitogen-activated protein kinase (MAPK) and dopaminergic synapse signaling pathways, 4 target proteins were detected based on our previous iTRAQ analysis. Rats were randomly divided into control group, model group, and electroacupuncture (EA) group. Except for the control group, all rats were subjected to 28 days of chronic restraint stress (CRS) protocols to induce depression. In the EA group, EA pretreatment at Baihui (GV20) and Yintang (GV29) was performed daily (1 mA, 2 Hz, discontinuous wave, 20 minutes) prior to restraint. The antidepressant-like effect of EA was measured by body weight and open-field test. The protein levels of DAT, Th, Mapt, and Prkc in the hippocampus were examined by using Western blot. The results showed EA could ameliorate the depression-like behaviors and regulate the expression levels of Prkc and Mapt in CRS rats. The effect of EA on DAT and Th expression was minimal. These findings implied that EA pretreatment could alleviate depression through modulating MAPK signaling pathway. The role of EA on dopaminergic synapse signaling pathways needs to be further explored.

Tao-He-Cheng-Qi Formula (THCQF) is a traditional Chinese medicine that has been proven to have antitumor effects. The aim of this study was to elucidate the molecular targets and mechanisms of THCQF against colon cancer and construct a prognostic model based on network pharmacology, bioinformatics analysis, and in vitro experiments.

This study investigated the effect of Angelica sinensis polysaccharides (APS-3c) on rat osteoarthritis (OA) model in vivo and rat interleukin-1-beta- (IL-1 β -) stimulated chondrocytes in vitro. APS-3c was administrated into rat OA knee joints and had protective effects on rat OA cartilage in vivo. Primary rat articular chondrocytes were cotreated with APS-3c and IL-1 β   in vitro. 2~50  μ g/mL APS-3c had no effect on chondrocytes viability, whereas it increased the proteoglycans (PGs) synthesis inhibited by IL-1 β . Microarray analysis showed that the significant changes were concentrated in the genes which were involved in PGs synthesis. RT-PCR confirmed that treatment with APS-3c increased the mRNA expression of aggrecan and glycosyltransferases (GTs) inhibited by IL-1 β but did not affect the mRNA expression of matrix-degrading enzymes. These results indicate that APS-3c can improve PGs synthesis of chondrocytes on rat OA model in vivo and IL-1 β -stimulated chondrocytes in vitro, which is due to the promotion of the expression of aggrecan and GTs involved in PGs synthesis but not the inhibition of the expression of matrix-degrading enzymes. Our findings suggest the clinical relevance of APS-3c in the prospective of future alternative medical treatment for OA.

Intestinal fibrosis is the main pathological process in Crohn's disease (CD); acupuncture and moxibustion can inhibit the process of fibrosis in CD rats, but the regulatory mechanism remains unknown. The present study observed the effect of moxibustion on the extracellular signal-regulated kinase (ERK) signaling pathway in the CD rat. The result shows that the phosphorylation of the Ras, Raf-1, MEK-1, and ERK-1/2 proteins and the expression of the corresponding mRNAs in the colon tissue of CD rat were significantly higher than the normal control group. Both treatments with mild moxibustion and with herb-separated moxibustion significantly reduced the expression of the Ras, Raf-1, MEK-1, and ERK-1/2 proteins and Ras and Raf-1 mRNA. MEK-1 and ERK-1/2 mRNA expression in each treatment group showed a downward trend, and the ERK-1/2 mRNA levels were significantly lower in the mild moxibustion group. It indicates that Ras, Raf-1, MEK-1, and ERK-1/2 are involved in the process of intestinal fibrosis in CD rats. Moxibustion can downregulate the abnormal expression of colonic Ras, Raf-1, MEK-1, and ERK-1/2 protein and mRNA levels in CD intestinal fibrosis in rats. Moxibustion may play a role in the treatment of CD intestinal fibrosis by regulating ERK signaling pathway.

Background. Yupingfeng Pulvis (HFBP) had played an active role in many diseases, especially respiratory tract infections. Exploring the possible prevention mechanism of HFBP may provide new ideas in clinical applications for this well-known herbal formula. Purpose. To study the possible mechanisms of therapy effect of HFBP on asthma mice via regulating the balance of Tregs and Th17 cells. Method. The female BALB/c mice were divided into five groups: control group, model group, prednisone (5.5 mg/kg) group, and 22 g/kg HFBP and 44 g/kg HFBP groups. Ovalbumin was used to make the asthma model of mice; the drug was ig administered daily after atomization for consecutive 15 d. The mice were killed after the last administration. The paraffin-embedded tissue sections of the lungs were stained by H&E. Tregs and Th17 cells in bronchoalveolar lavage fluid were detected by flow cytometry. IL-4, TGF-β, and TNF-α in the serum were detected by ELISA assay. Results. HFBP could alleviate the inflammation in the lung tissue of mice, decrease the proportion of Th17 cells, and increase the proportion of Treg cells in bronchoalveolar lavage fluid. HFBP could decrease IL-4 and TNF-α level and increase TGF-β level in blood. Conclusion. HFBP could treat the asthma through impacting the balance of Th17 cells and Treg cells as well as the levels of related inflammatory cytokines in asthma mice.

The TLR2/NF-κB signaling pathway plays an important role in the pathomechanism of ulcerative colitis (UC); acupuncture and moxibustion can improve the damage in colonic tissues of UC, but the regulatory mechanism remains unknown. This study observed the effect of moxibustion on the TLR2/NF-κB signaling pathway at the Tianshu (ST25) and Qihai (CV6) acupuncture points in the UC rat. The result shows that TLR2, IRAK1, and IKK-b mRNA and protein levels in the colonic mucosa were significantly higher in the UC rats than in the control rats. Herb-partitioned moxibustion reduced the expression of TLR2, IRAK1, and IKK-b mRNA and proteins in the UC rats. Similarly, the expression of NF-κB was significantly increased and IFN-β and IL-10 were significantly decreased in the colonic mucosa of UC rats, but herb-partitioned moxibustion reduced the expression of IFN-β and upregulating the expression of IFN-β and IL-10 significantly. It indicates that herb-partitioned moxibustion can inhibit the expression of multiple signaling molecules of the TLR2 pathway effectively, and it may modulate the excessive local immune response by inhibiting TLR2 signaling, thereby promoting the repair of damaged colonic mucosa.

Methamphetamine (Meth) is a highly addictive substance and the largest drug threat across the globe. There is evidence to indicate that Meth use has serious damage on central nervous system (CNS) and heart in several animal and human studies. However, the connection in the process of Meth addiction between these two systems has not been determined. Emerging data suggest that extracellular vesicles (EVs) carrying behavior-altering microRNA (miRNAs) play a crucial role in cell communication between CNS and peripheral system. Rhynchophylline (Rhy), an antiaddictive alkaloid, was used to protect the brain and heart from Meth-induced damage, which has caught our attention. Here, we used Meth-dependent conditioned place preference (CPP) animal model and cell model to verify the protective effect of Rhy-treated EVs. Further, small RNA sequencing analysis, qPCR, dual-luciferase reporter assay, and transfection test were used to identify the key EVs-encapsulated miRNAs, isolated from cultured H9c2 cells with different treatments, involved in the therapeutic effect and the underlying mechanisms of Rhy. The results demonstrate that Rhy-treated EVs exert protective effects against Meth dependence through the pathway of miR-183-5p-neuregulin-1 (NRG1). Our collective findings provide novel insights into the roles of EVs miRNAs in Meth addiction and support their potential application in the development of novel therapeutic approaches.

Ginsenoside Rg1 is a major component of ginseng with antioxidative and antiaging effects, which is a traditional Chinese medicine. In this study, we investigated the potential spillover and mechanism of action of Rg1 on LiCl-driven hematopoietic stem cell aging.

Major depressive disorder (MDD) is a chronic disease that adversely affects mood and cognition. In this study, we randomly divided the rats into control group (C), model group (M), fluoxetine group (F), and acupuncture group (A), used open-field test to ascertain whether acupuncture affects chronic restraint stress (CRS) induced depression-like behaviors of rats, and explored the antidepressant mechanism of acupuncture at the molecular level of transcriptome in the frontal cortex of CRS rats by RNA-sequencing (RNA-seq). According to differentially expressed genes (DEG) analysis, we identified 134, 46, and 89 response genes differentially expressed in C versus M, F versus M, and A versus M, respectively. Through Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, we identified the gene sets involved in extracellular space, inflammatory response, Toll-like receptor signaling pathway, chemokine signaling pathway, and TNF signaling pathway. In this study, RNA-seq technology was used to investigate the frontal cortex genome-wide transcriptomes in depression rats under CRS, which suggested that the antidepressant effect of acupuncture is effective and has a multitarget characteristic, which may be related to amino acid metabolism and inflammatory pathways, especially the Toll-like receptor signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway.

Gukang capsule (GKC) is a traditional Chinese medicine formulation which has been used extensively in the clinical treatment of bone fractures. However, the mechanisms underlying its effects on fracture healing remain unclear.