Low CBS expression can identify patients who benefit from adjuvant chemotherapy in gastric cancer.

Aim: To explore the clinical significance of Cystathionine beta-synthase (CBS) expression in gastric cancer (GC).Research design and methods: CBS expression and clinicopathological/follow-up information of patients with gastric cancer undergoing operation were collected from The Cancer Genome Atlas (TCGA) database. The association of CBS expression with patients' overall survival (OS) was determined in the entire cohort and different subgroups. Validation was performed in two external cohorts from NCBI Gene Expression Omnibus (GEO) database. The estimated drug response of the tumors with different CBS expressions was characterized. The potential CBS-related cellular pathways in chemoresistance were explored.Results: High CBS was associated with poor OS in patients receiving adjuvant chemotherapy (ACT) but not those without ACT. And ACT was associated with favorable OS in patients with low CBS expression but not those with high CBS expression. The results were verified in two external cohorts. Drug response prediction suggested that patients with low CBS expression showed high sensitivity to 5-Fluorouracil. Gene Set Enrichment Analysis (GSEA) suggested that CBS might contribute to GC chemoresistance via modulating many cellular pathways, including down-regulating apoptosis and P53 pathways while up-regulating DNA repair pathway.Conclusion: Low CBS expression can predict the benefit from ACT in GC.

Chemokine CXCL1 in serum mediates the antinociceptive effect of manual acupuncture at ST36.

BACKGROUND: Inflammatory pain is the most common type of pain encountered clinically. The analgesic effect of acupuncture has been well-documented. OBJECTIVE: The aim of this study was to investigate the involvement of chemokine CXCL1 in the serum on manual acupuncture (MA)-induced antinociception. METHODS: Rats with inflammatory pain of the right hind paw were induced by intraplantar (i.pl.) administration of complete Freund's adjuvant (CFA). After wards, the CFA-injected rats were treated daily with MA at ST36 from Day 1 to Day 7, and thermal nociceptive thresholds (paw withdrawal latency; PWL) were analyzed. The concentration of CXCL1 in the serum of the rats was measured by enzyme-linked immunosorbent assay (ELISA) after the first and the last MA treatment. Subsequently, the rats were injected with two doses (5 or 10 µg) of recombinant CXCL1 through the tail vein daily from Day 1 to Day 7 or injected with two doses (6.4 or 16 µg) of anti-CXCL1 antibody using the same methods and course at 30 min before MA, and the PWLs were measured again. Finally, naloxone (500 µg, 0.1 mL) was administered by i.pl. injection into the inflamed paw 5 min before the last MA treatment or last injection of recombinant CXCL1. RESULTS: MA significantly increased the PWLs and upregulated the expression of serum CXCL1 in the CFA-injected rats. Without acupuncture, repeated tail vein injection of recombinant CXCL1 showed an analgesic effect on CFA-induced inflammatory pain. Conversely, the neutralization of serum CXCL1 by anti-CXCL1 antibody decreased MA-induced antinociception in a time-dependent manner. Anti-CXCL1 antibody injected just once before the first MA did not affect MA-induced antinociception. The analgesic effects of MA and recombinant CXCL1 were reversed by an i.pl. injection of naloxone. CONCLUSION: This study indicates MA at ST36 had an analgesic effect on inflammatory pain and found a novel function of CXCL1. Increased serum CXCL1 had an antinociceptive effect on inflammatory pain induced by CFA. CXCL1 in serum appeared to be a key molecule involved in the peripheral mechanism of MA-induced antinociception. The analgesic effect of MA or recombinant CXCL1 on inflammatory pain might be mediated through a peripheral opioid pathway, which needs further investigation.

Applying Complex Network and Cell-Cell Communication Network Diagram Methods to Explore the Key Cytokines and Immune Cells in Local Acupoint Involved in Acupuncture Treating Inflammatory Pain.

Manual acupuncture (MA) can effectively treat a variety of diseases, but its specific mechanism remains unclear. The "acupoint network" activated by MA participates in MA signal transduction, in which immune-related cells and cytokines play an important role. However, which cells and cytokines in the acupoint have changed after MA? What is the network relationship between them? Which cells and cytokines may play the most important role in MA effect? These problems are unclear. In this study, on the basis of affirming the analgesic, detumescence, and anti-inflammatory effect of MA, the concentration of 24 cytokines in ST36 acupoint in rats with inflammatory pain after MA treatment was detected by multiplex immunoassay technology. Then, using statistical and complex network and cell-cell communication (CCC) network diagram method to analyze the detected data depicts the network relationship between the cytokines and related cells objectively and establishes cytokine connection network and CCC network, respectively. The results showed that MA reinforced communication intensity between cells while reducing the overall correlation intensity. On this basis, the key cytokines and key cells at three MA time-points were screened out, cytokines IL-6, MCP-1, fibroblasts cell, and monocyte macrophage screened by the three methods at three MA time-points might be the key cytokines or key cells. After that, we detected the macrophages in ST36 acupoint by flow cytometry and immunofluorescence and found that the relative amount of macrophages increased significantly after MA, especially the macrophage of the dermis of skin. This study provided a basis for revealing the initiated mechanism of MA effect.

Acupuncture Alleviates Rheumatoid Arthritis by Immune-Network Modulation.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory and debilitating disease that involves the systemic imbalance of the immune network. Previous studies have shown that acupuncture can help treat RA. However, its specific mechanisms are not fully understood. Thus, the present study was designed to clarify the mechanisms of acupuncture acted on RA via immune network modulation using complete Freund's adjuvant (CFA)-induced arthritic rats. Results revealed that manual acupuncture (MA) could alleviate the inflammation and pain of infected joints. Moreover, MA could effectively stimulate the innate immune cytokines (IL-1[Formula: see text], IL-1[Formula: see text], IL-6, IL-7, IL-18, TNF-[Formula: see text]) and adaptive immunity cytokines (IL-2, IL-12, IFN-[Formula: see text], IL-4, IL-5, IL-10, IL-13, IL-17) as the main part of the immune response and repaired damage of RA. These complex immunomodulatory processes were analyzed quantitatively by cell-cell communication (CCC) networks. The CCC networks demonstrated that the immune networks were enhanced with the development of RA, while MA enhanced the immune networks in the early stage to act on RA and promoted the immune-network to a normal level at the late stage. Moreover, we found that monocyte/macrophage and endothelial cells were the key cells of innate immunity and body cells; TH1, TH2 and B cells were the key cells of adaptive immunity, which were also the main target cells for MA regulation.

Applying Statistical and Complex Network Methods to Explore the Key Signaling Molecules of Acupuncture Regulating Neuroendocrine-Immune Network.

The mechanisms of acupuncture are still unclear. In order to reveal the regulatory effect of manual acupuncture (MA) on the neuroendocrine-immune (NEI) network and identify the key signaling molecules during MA modulating NEI network, we used a rat complete Freund's adjuvant (CFA) model to observe the analgesic and anti-inflammatory effect of MA, and, what is more, we used statistical and complex network methods to analyze the data about the expression of 55 common signaling molecules of NEI network in ST36 (Zusanli) acupoint, and serum and hind foot pad tissue. The results indicate that MA had significant analgesic, anti-inflammatory effects on CFA rats; the key signaling molecules may play a key role during MA regulating NEI network, but further research is needed.

[Literature study for acupoint selection rule of rheumatoid arthritis treated with acupuncture].

To explore the clinical acupoint selection rule of rheumatoid arthritis(RA) treated with acupuncture by literature analysis. The related articles were retrieved in 6 Chinese and English databases,including CNKI,VIP,WANFANG,PubMed,Medline and Cochrane. We established a holistic acupoint database and a disease location acupoint database. The results show that there are 120 acupuncture prescriptions and 143 acupoints,with the highest frequency of Zusanli(ST 36). Local acupoints are mainly used for disease locations. The highest acupoin-tcombination frequency of 32 for mandibular joint shows Kunlun(BL 60) and Jiexi(ST 41);22 for finger joint,Baxie(EX-UE 9) and Zusanli(ST 36);28 for wrist joint,Yangxi(LI 5) and Yangchi(TE 4);24 for elbow joint,Quchi(LI 11) and Zusanli(ST 36);21 for shoulder joint,Jianyu(LI 15) and Zusanli(ST 36);13 for spine joint,Yaoyangguan(GV 3) and Shenzhu(GV 12);18 for hip joint,Zhibian(BL 54) and Huantiao(GB 30);20 for knee joint,Shenshu(BL 23) and Yanglingquan(GB 34);32 for ankle joint,Kunlun(BL 60) and Jiexi(ST 41);22 for toe joint,Baxie(EX-UE 9) and Zusanli(ST 36);25 for whole body joints,Yanglingquan(GB 34) and Zusanli(ST 36). Thirty new acupoint prescriptions are found by entropy clustering analysis for different disease regions induced by RA. There exists the acupoint selection rule for acupuncture treating RA and the new prescriptions need to be clinical verification.

Efficacy and safety of manual acupuncture manipulations with different frequencies on epigastric pain syndrome (EPS) in functional dyspepsia (FD) patients: study protocol for a randomized controlled trial.

BACKGROUND: Manual acupuncture (MA) manipulations are one of the key factors influencing acupuncture effects in traditional Chinese medicine theory. Different MA manipulations contain different stimulating parameters, thus generating different acupuncture responses or effects. Evidence has demonstrated that acupuncture is effective for functional dyspepsia (FD). However, the effects of different stimulating parameters of MA manipulations on FD remain unclear. METHODS/DESIGN: This study is a randomized controlled trial with a four-arm, parallel-group structure. Patients with FD with epigastric pain syndrome (EPS) will be included and randomly allocated into four groups: three MA manipulation groups (separately treated with a frequency of 1 Hz, 2 Hz, or 3 Hz) and a control group. All groups will receive omeprazole as a basic treatment and acupuncture: in the MA manipulation groups, the needles will be manipulated manually with three different frequencies on the basis when de qi is reached, while in the control group, the needles will be inserted without any manipulation. All patients will receive acupuncture treatment of five consecutive sessions per week for 2 weeks and be followed up at 4, 8, and 12 weeks. The primary outcomes of the study include patients' response to the treatment. The secondary outcomes include dyspeptic symptoms, quality of life, mental status, fasting serum gastrin, motilin, and ghrelin concentrations, and adverse events. The protocol was approved by the Ethics committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (2016-K-057-01). DISCUSSION: The aim of this study is to evaluate the efficacy and safety of MA manipulations with different stimulating parameters (different frequencies) on EPS in patients with FD. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IOR-16008189 . Registered on 30 March 2016.

[Development of Researches on Cytokine Mechanisms in Analgesia and Anti-inflammation in Acupuncture Therapy for Rheumatoid Arthritis].

Cytokines are closely related to the occurrence and development of rheumatoid arthritis(RA). Acupuncture exerts anti-inflammatory and analgesic effects via elevating anti-inflammatory cytokine level and reducing pro-inflammatory cytokine level and regulating Th 1/Th 2 balance, which reflects the dual directional regulatory effect of acupuncture. However, problems exist in the current researches, such as inadequate depth, limited breadth and not so up-to-date research focus. The mediocre research level and the phenomena of some contradictory results among studies also need being concerned. Therefore, progress may be attained if a holistic, dynamic and networked study is conducted on the influence of acupuncture on cytokines by combining the latest progress in the mechanisms of network of cytokines and neuroendocrine immune network, and high throughput cytokine capture assay. In this way, the mechanism of cytokines in multi-targets (such as local joints, peripheral blood circulation, central nervous system) involving the effects of acupuncture in improving RA will be known more.

A Randomized Controlled Trial of Puncturing and Bloodletting at Twelve Hand Jing Points to Treat Acute Carbon Monoxide Poisoning as Adjunct to First Aid Treatment: A Study Protocol.

Background. Acute carbon monoxide poisoning (ACOP) is a significant cause of morbidity and mortality in many countries. Twelve Hand Jing Points (THJP) have been believed to be effective to treat all kinds of emergency calls in traditional Chinese medicine (TCM) for more than 3000 years. This randomized controlled trial (RCT) is designed to evaluate the effectiveness of THJP in curing acute carbon monoxide poisoning in first aid treatment. This paper reports the protocol of the trial. Methods/Design. This RCT is a multicenter, randomized, controlled study undergoing in China. The compliant patients are divided into the bloodletting group and standard of care group. With first aid treatments given to both of the groups, the bloodletting group is bleeding at THJP upon being hospitalized. Primary outcomes and secondary outcomes will be measured and compared between these two groups. Before treatment, immediately after treatment, and 30 minutes, 1 hour, and 4 hours after treatment, patients' basic vital signs and state of consciousness were observed. Before treatment and 1 and 4 hours after treatment, carboxyhemoglobin concentration in venous blood samples was detected. Discussion. The objective of this study is to provide convincing evidence to clarify the efficacy and safety of THJP for early treatment of acute carbon monoxide poisoning.

Synthesis and biological activity of polyprenols.

The polyprenols and their derivatives are highlighted in this study. These lipid linear polymers of isoprenoid residues are widespread in nature from bacteria to human cells. This review primarily presents the synthesis and biological activities of polyprenyl derivatives. Attention is focused on the synthesis and biological activity of dolichols, polyprenyl ester derivatives and polyprenyl amines. Other polyprenyl derivatives, such as oxides of polyprenols, aromatic polyprenols, polyprenyl bromide and polyprenyl sulphates, are mentioned. It is noted that polyprenyl phosphates and polyprenyl-linked glycosylation have better antibacterial, gene therapy and immunomodulating performance, whereas polyprenyl amines have better for antibacterial and antithrombotic activity. Dolichols, polyprenyl acetic esters, polyprenyl phosphates and polyprenyl-linked glycosylation have pharmacological anti-tumour effects. Finally, the postulated prospect of polyprenols and their derivatives are discussed. Further in vivo studies on the above derivatives are needed. The compatibility of polyprenols and their derivatives with other drugs should be studied, and new preparations of polyprenyl derivatives, such as hydrogel glue and release-controlled drugs, are suggested for future research and development.

Strong Manual Acupuncture Manipulation Could Better Inhibit Spike Frequency of the Dorsal Horn Neurons in Rats with Acute Visceral Nociception.

Afferent impulses from visceral nociception can be regulated by acupuncture at spinal cord level; however, the effects of different manual acupuncture (MA) manipulations on the afferent impulses are still unknown. Here, we analyzed the spike frequency of excitatory gastric-related wide dynamic range (WDR) neurons in spinal dorsal horn (SDH) following acute gastric distension (GD) in rats and compared their responses to MA manipulations with four different frequencies (0.5, 1, 2, and 3 Hz) at Zusanli (ST36). Results indicated that the spike frequency was increased by acute GD stimulation. Under acute GD circumstances, the spike frequency was further activated by weak MA stimulation (0.5 and 1 Hz), while being significantly inhibited by strong MA stimulation (2 and 3 Hz). After 10 minutes of the strong MA stimulation, same intensity of acute GD caused less spike frequency. Our previous researches had demonstrated that different MA manipulations could increase spike frequency in an intensity-dependent manner in normal rats; these findings suggest that acupuncture may have different modulatory effects depending on the state of the stomach. Since neuronal spike frequency was related to the level of nociception, the results suggest that strong MA manipulation may have better effect on acute visceral nociception.

[ITD mutation burden for the prognosis in FLT3-ITD positive acute myeloid leukemia patients].

OBJECTIVE: To explore the impact of ITD mutation characteristics on the overall survival (OS) and complete remission duration (CRD) in FLT3-ITD positive non-M3 acute myeloid leukemia (AML). METHODS: Capillary electrophoresis was used to detect the FLT3-ITD characteristics after PCR amplication. Single or multiple mutations were identified by the numbers of peak. FLT3-ITD mutation burden was calculated by the peak area of mutant divided by the wild-type and mutant peak areas. Clinical data was collected and followed up in the FLT3-ITD mutation patients. RESULTS: Multiple ITD mutations were common in patients aged 60 and above. Patients with single ITD mutation had higher percentage of blasts in bone marrow than multiple ITD mutations (0.758 vs 0.638, P=0.028). The numbers and length of FLT3-ITD mutation had no impact on prognosis. Patients with less than 10% of ITD mutation burden showed no difference with the intermediate-risk c-kit group in OS and CRD, but the two groups had longer OS and CRD than ITD mutation burden above 10% (OS: undefined, undefined, 9.9 months, P<0.05; CRD: undefined, undefined, 6.7 months, P<0.05). In patients with ITD mutation burden above 10%, cases with NPM1 or CEBPA mutation alone had markedly longer CRD than ITD mutation alone (25.0 vs 5.1 months, P=0.003), while OS were similar (11.4 vs 8.0 months, P>0.05). CONCLUSION: Non-M3 AML patients with less than 10% FLT3-ITD mutation burden had a better prognosis than those above 10%.

[Analysis on literature regarding acupuncture-moxibustion with high impact factor journal of SCI during the recent 5 years].

The status of acupuncture-moxibustion is more and more recognized by mainstream medicine in the world in recent years, and literature regarding acupuncture-moxibustion with high impact factor (IF) published in the worldwide mainstream medicine journals is also gradually growing by years. To understand the situation of related literature, literature regarding acupuncture-moxibustion with IF of more than 10 in Science Citation Index (SCI) during the recent 5 years was retrieved. The number, the types, the diseases involved, the publishing states of the acquired articles and the source, the citation, the IF of the publishing journals were analyzed and summarized. Additionally, some of the research foci, the new research tendencies and the deficiencies of research were discussed. The thoughts and suggestions are expected to be provided for further research of acupuncture.

Efficacy and safety of transcutaneous electrical acupoint stimulation to treat muscle spasticity following brain injury: a double-blinded, multicenter, randomized controlled trial.

OBJECTIVE: This study was aimed at evaluating the clinical efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) to treat muscle spasticity after brain injury (Chinese Clinical Trial Registry: ChiCTR-TRC-11001310). METHODS: A total of 60 patients with muscle spasticity after brain injury were randomized to the following 3 groups: 100, 2, and 0 Hz (sham) TEAS. The acupoints Hegu (LI4)--Yuji (LU10) and Zusanli (ST36)--Chengshan (BL57) on the injured side were stimulated at 0, 2, or 100 Hz, 5 times per week for 4 weeks. The patients were followed up for 1 and 2 months after the treatments. The effects of the treatments on muscle spasticity at the wrist, thumb, the other 4 fingers, elbow, shoulder, knee, and ankle were evaluated by the Modified Ashworth Scale, and the effects on disability were assessed by the Disability Assessment Scale. The walking capability was evaluated by the Holden functional ambulation classification score. The overall performance was assessed by the Global Assessment Scale score and the improved Barthel Index. The safety of the treatments administered was also monitored. RESULTS: The wrist spasticity was significantly reduced from baseline at weeks 2, 3, and 4 of treatment and at the 1- and 2-month follow-up visits in the 100 Hz group (P < 0.01). Compared with 2 Hz or sham TEAS, 100 Hz TEAS decreased wrist spasticity at weeks 2, 3, and 4 of treatment and 1 month after treatment (P < 0.001). The other endpoints were not affected by the treatments. No treatment-emergent adverse events were reported during treatments and follow-up visits. CONCLUSIONS: TEAS appears to be a safe and effective therapy to relieve muscle spasticity after brain injury, although large-scale studies are required to further verify the findings. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-11001310 http://www.chictr.org.

[Acupoint: the sensor of the information in the organic body].

Based on the structure and function of acupoint and in association of the definition and principle of sensor, the acupoint is the sensitive element, being sensitive to the physical stimulation with acupuncture and moxibustion and sensitively responded to the disorders; the acupoint is the sensing element, transforming the changes of the acupoint information via the complicated internet conduction, integration and regulation, so as to generate the effects on organic body; the acupoint is the conversion element, transforming every irritation into the bioelectric signal or optical signal so that the organic body could recognize it. Therefore, the acupoint is regarded as the sensor of information in the organic body.

[Quality assessment of randomized controlled trials on wenxin granule for treatment of atrial fibrillation].

OBJECTIVE: To investigate the statement on randomized controlled trials on Wenxin granule for treatment of atrial fibrillation and to judge whether those trials could offer high quality evidence or not, thus improve design level and quality. METHOD: RCTs were searched from home and abroad about atrial fibrillation treated with Wenxin granule, which reported before October, 2010. Jadad scale and CONSORT statement were used. RESULT: There were 66 RCTs retrieved that met inclusion criteria. Using Jadad rating scale, only 2 literatures gain score 4 and 1 literature gains score 3, 54 literatures gain score 2, 7 literatures gain score 1, 2 literatures gain score 0. Only 2 literatures described random number table as the method of grouping. None of the RCTs was reported the allocation concealment. Only 1 literature was used blinding. Fifty-nine literatures were mentioned the lost to follow-up conditions. According to the CONSORT standards, only six literatures (9.1%) mentioned the method of generating the random sequence. Four literatures (6.1%) were quasi-random. Nineteen literatures (28.8%) had inclusion criteria. Six literatures (9.1%) had the follow-up record. Fifty one literatures (77.3%) described the adverse events. None had the estimation of the sample size, intention-to-treat analysis and stratified analysis. None had the ethical approval or informed consent. CONCLUSION: The quality of clinical trials of Wenxin granule in treating atrial fibrillation needs to be improved.