Design, synthesis and biological evaluation of novel benzimidazole-derived p21-activited kinase 4 (PAK4) inhibitors bearing a 4-(4-methylpiperazin-1-yl)phenyl scaffold as potential antitumor agents.

A series of novel 6-(4-(4-methylpiperazin-1-yl)phenyl)-1H-benzo[d]imidazole-based p21-activited kinase 4 (PAK4) inhibitors were designed and synthesized based on the structure of lead compound GNE-2861 and that of anticancer inhibitors reported in our previous studies. All target compounds so designed were preliminarily screened in vitro for anti-tumor potency through kinase inhibitory assays and MTT assays, which revealed that most compounds exhibited significant inhibitory effects on PAK4 enzyme as well as prominent antiproliferative activities against four cancer cell models (A549, NCI-H1975, MDA-MB-231 and SK-BR-3) and low damage to healthy cells. In particular, the hit compound 12i was identified as the most effective and rather selective compound both at the enzyme and cellular level.

[Bibliometric analysis on the literature characteristics of animal experiment research with acupuncture and moxibustion].

Objective: To compare the diversities in the literature characteristics of animal experiments with acupuncture and moxibustion (acu-moxibustion) published in both Chinese and English, so as to summarize the similarities and differences in the reporting content for the animal experiment research with acu-moxibustion in the journals at home and abroad.

Methods: The articles of animal experiments with acu-moxibustion published from 2016 to 2018 were searched from CNKI, Wanfang, SinoMed, PubMed and Web of Science databases. The articles were screened according to the inclusion and exclusion criteria, and the database was established by importing the essential information, e.

[κ-opioid receptor is involved in electroacupuncture analgesia via inhibition of spinal microglial Toll-like receptor 4 in neuropathic pain rats].

Objective: To observe the effect of electroacupuncture (EA) on the expression of lumbar spinal κ-opioid receptor (KOR) and Toll-like receptor 4(TLR4) in microglia in neuropathic pain rats, so as to explore the role of cross-talk between KOR and TLK4 in EA-induced alleviation of chronic neuropathic pain.

Methods: Wistar male rats were randomized into control, model, EA and EA plus KOR inhibitor (EA+inhibitor) groups (=18 in each group). The neuropathic pain model was established in rats by ligature of the right sciatic nerve.

[Spinal cord Toll like receptor 4 and its co-stimulatory molecule heat shock protein 90 may parti-cipate in electroacupuncture analgesia in rats with chronic neuropathic pain].

Objective: To observe the effect of electroacupuncture (EA) on the expression of Toll like receptor 4(TLR4)and heat shock protein 90(HSP90) in the spinal cord of rats with chronic constriction injury (CCI) of sciatic nerve, so as to explore the mechanism of spinal cord TLR4 and HSP90 in alleviating chronic neuropathic pain by EA.

Methods: Male Wistar rats were randomized into control, model, EA, HSP90 inhibitor (inhibitor) and EA+ inhibitor groups (=10 in each group). The neuropathic pain model was established by ligature of the right sciatic nerve to induce CCI.

[How to improve the quality of histological pictures in the manuscripts of ].

Histological pictures are important parts of medical research articles, and a good histological picture not only visualizes the content of the article, but also makes it easier for readers to understand. With the rapid development of microscopic technology and image processing technology, journals have higher requirements for the quality of histological pictures and more strict requirements for the editing and annotation of pictures. Based on an analysis of the current status of histological pictures in the articles of , this article proposes our suggestions and Methods for rational use of histological pictures, so as to provide a reference for improving the quality of histological pictures in the articles published in .

[High Mobility Group Box 1/ CD 24 Receptor/β-EP Signaling in "Zusanli" (ST 36) Region Contributes to Electroacupuncture Analgesia in Rats with Neuropathic Pain].

Objective: To observe the effect of electroacupuncture (EA) on the expression of high mobility group box 1 (HMGB 1) and its receptor CD 24 proteins and β-endorphin (β-EP) content in "Zusanli" (ST 36) region in rats with chronic constriction injury (CCI), so as to explore its mechanisms underlying pain relief.

Methods: Thirty male Wistar rats were rando-mized into control, CCI model and EA groups (＝ 10 rats in each). The neuropathic pain model was established by ligature of the left sciatic nerve to induce CCI in the model and EA groups, and sham operation was performed in rats of the control group.

[Effect of Electroacupuncture Intervention on Expression of Pain Sensory and Affective Proce- ssing-related µ-opioid Receptor, etc. in the Amygdala in Chronic Neuropathy Pain Rats].

Objective: To observe the effect of electroacupuncture (EA) on expression of pain sensory and affective processing-related µ-opioid receptor (MOR), glutamatergic AMPA receptor subunit GIuA 1, extracellular signal-regulated kinase (ERK 1/2), cAMP response element binding protein(CREB) in the amygdala in chronic constrictive injury (CC) + negative affection(NA) rats, so as to reveal its mechanism underlying pain relief.

Methods: A total of 32 male Wistar rats were randomized into normal control, model, EA, and anesthesia+ EA (AEA) groups (n = 8 in each group). The neuropathic pain NA model was established by ligation of the left sciatic nerve and repeated electrical stimulation of the paw-bottom in the pain-paired compartment.

Analysis and Thoughts about the Negative Results of International Clinical Trials on Acupuncture.

An increasing number of randomized controlled trials (RCTs) of acupuncture have proved the clinical benefits of acupuncture; however, there are some results that have shown negative results or placebo effects. The paper carried out an in-depth analysis on 33 RCTs in the 2011 SCI database, the quality of the reports was judged according to Jadad scores, and the "Necessary Information Included in Reporting Interventions in Clinical Trials of Acupuncture (STRICTA 2010)" was taken as the standard to analyze the rationality of the therapeutic principle. The difference between the methodology (Jadad) scores of the two types of research reports did not constitute statistical significance (P > 0.

[On the necessity of intellectual property rights involving standardization of acupuncture and moxibustion therapies].

In the process of working out and implementing standardization of acupuncture-moxibustion (acu-moxi) therapy, the issue of intellectual property rights has been frequently involved. Whether is the standardization inevitably involved in intellectual property rights? A reasonable answer to this question is definitely of important realistic guiding value and significance for acu-moxi standardization work. For this reason, authors of the present paper sum up historical development of correlation between acu-moxi standardization and intellectual property rights, and fully analyze the related causes under the conditions of knowledge economy from 1) increasing protection of acu-moxi intellectual property rights, 2) intrinsic requirements for raising the standardization level of acu-moxi, 3) profits drive of the intellectual property rights owners, and 4) increasing impetuous international economic trade competition.

[Progress of researches on mechanisms of acupuncture underlying improvement of depression in the past five years].

Depression is a state of low mood and aversion to activity that has a negative effect on the patient's thoughts, behavior, feelings, and physical well-being. In the past five years, a significant progress has been made in understanding the mechanism of acupuncture therapy for improving depression. In the present paper, the authors summarize mechanisms of acupuncture for depression from 1) upregulating levels of monoamine neurotransmitters, gamma-aminobutyric acid, 5-HT, receptor binding, and hypothalamic neuropeptide Y, beta-endorphine, and mu-receptor expression, and down-regulating hippocampal glutamate content, etc.

[Involvement of hippocampal NO/PKG signaling pathway in the accumulative analgesic effect of electroacupuncture stimulation of "Zusanli" (ST 36)-"Yanglingquan"(GB 34) in chronic neuropathic pain rats].

Objective: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST 36)-"Yanglingquan"(GB 34) on pain behavior and expression of hippocampal neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase(iNOS)and cGMP-dependent protein kinase (PKG) mRNA in rats with chronic neuropathic pain so as to analyze its mechanism underlying analgesia.

Methods: Forty male Wistar rats were randomly divided into control, CCI model, EA-2 Hz, EA-2 Hz/15 Hz, EA-100 Hz groups, with 8 cases in each group. Chronic neuropathic pain model was established by ligature of the left sciatic nerve under anesthesia (Urethane + Alpha-Chloralose) except rats in the control group.

[Analysis on shortcomings or insufficiencies of some manuscripts for publication in acupuncture research].

Based on the manuscripts delivered to Acupuncture Research, the author of the present paper analyzes some current shortcomings existing in scientific research work of acu-moxibustion. The main shortcomings are 1) insufficient experimental design, 2)inopportune intervention time, 3) indexes unable to explain the underlying mechanism of therapeutic effects, 4) unfounded exaggeration of the roles of acu-moxibustion therapy, and 5) improper conclusion. In addition, the author gives some typical examples to show these shortcomings or insufficiencies, so as to provide references for researchers in avoiding some defects in experimental designs and in giving reasonable explanations about their research findings in the future.

[Effects of electroacupuncture at "Futu"(LI 18), etc. on pain threshold and cervico-spinal mGlu receptor 5/cAmp/CREB signaling in rats with neck incision pain].

Objective: To observe the effect of electroacupuncture (EA) at "Futu" (LI 18),etc. on the pain threshold and expression of metabotropic glutamate receptor subtype 5 (mGluR 5), cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), cAMP responsive element binding protein (CREB) genes in the cervico-spinal dorsal region in rats with neck incision pain so as to analyze its underlying analgesic mechanism in performing thyroid surgery.

Methods: Forty male Wistar rats were randomly divided into control, model, Futu (LI 18), Hegu (LI 4)-Neiguan (PC 6), Zusanli (ST 36)-Yanglingquan (GB 34) groups, with 8 cases in each group.

[Effects of electroacupuncture of "Futu" (LI 18), etc. on pain behavior and expression of GABA receptor subunit genes in cervical spinal cord in rats with thyroid regional pain].

Objective: To observe the effect of electroacupuncture (EA) at different acupoints on the expression of gamma aminobutyric (GABA) receptor (R) subunit genes in the cervical spinal cord in rats with thyroid regional inflammatory pain so as to analyze its analgesic mechanism for thyroid surgery.

Methods: A total of 50 Wistar rats were randomized into control, model, Futu (LI 18), Hegu (LI 4)-Neiguan (PC 6, LI 4-PC 6), Zusanli (ST 36)-Yanglingquan (GB 34, ST 36-GB 34) groups, with 10 rats in each group. Thyroid regional pain model was established by subcutaneous injection of 2.

[Research on basic questions of intellectual property rights of acupuncture and moxibustion].

Along with the modernization and internationalization of acupuncture-moxibustion (acu-moxibustion), the issue of intellectual property rights has been becoming prominent and remarkable increasingly. In the present paper, the authors explain the basic issues of acu-moxibustion learning from the concept, scope, subject, object, contents and acquisition way of intellectual property rights. To make clear these questions will help us inherit and carry forward the existing civilization achievements of acu-moxibustion, and unceasingly bring forth new ideas and further improvement in clinical application, so as to serve the people's health in a better way.

[Effects of electroacupuncture at "Futu" (LI 18), etc. on expression of spinal 5-HT 1 AR mRNA, 5-HT 2 AR mRNA and protein in rats with neck incision pain].

Objective: To observe the effect of electroacupuncture (EA) at bilateral "Futu" (LI 18), etc. on the expression of 5-HT 1 A receptor (R) mRNA, 5-HT2 AR mRNA and protein in the spinal cord of rats with neck incision pain, so as to explore its underlying mechanism in relieving incision pain.

Methods: A total of 48 Wistar rats were randomly divided into control, model (incision pain), Futu (LI 18), Hegu (LI 4)-Neiguan (PC 6, LI 4-PC 6), Zusanli (ST 36)-Yanglingquan (GB 34) cervical cord (ST 36-GB 34 C) and lumbar cord (ST 36-GB 34 L) groups.

[Effect of acupuncture on contents of beta-endorphin in the plasma and hypothalamus in rats with stress-induced gastric mucosal injury].

Objective: To explore the mechanism of acupuncture in preventing and treating stress-induced gastric mucosal injury from the view of brain-gut axis.

Methods: Forty male Wister rats were randomly divided into normal control, model 1, treatment, model 2 and prevention groups (n=8). Gastric mucosa injury model was established by intragastric perfusion of dehydrated alcohol (1.

[Effects of scalp acupuncture on expression of hippocampal MMP-9 in cerebral ischemia injury rats].

Objective: To observe the effect of scalp-acupuncture on the expression of matrix metalloproteinase 9 (MMP-9) in the endothelium of the microvessels in the hippocampal CA 3 area in local cerebral ischemia (CI) rats, so as to study its underlying mechanism in improving CI.

Methods: Eighty male Wistar rats were randomized into normal control (n = 8), sham-operation (n = 8), CI model (n = 32), and scalp-acupuncture (n = 32) groups. The later two groups were further equally and respectively divided into 1, 3, 5 and 10 d subgroups.

[Effect of electroacupuncture of "Baihui" (GV 20)-"Yintang" (EX-HN 3) on the expression of glucocorticoid and glucocorticoid receptor mRNA of the chronic stress model rats].

Objective: To observe the effect of electroacupuncture (EA) on the expression of glucocorticoid (GC) mRNA and GC in the hippocampus, hypothalamus and pituitary in depression rats so as to study its mechanism underlying EA-resisting depression.

Methods: Seventy SD rats were randomized into normal control, model, Fluoxetine (Flu), constraint-stress, EA, RU 486 (an antagonist of GC) and EA+ RU 486 groups (n = 10/group). Chronic depression model was established by lonely raising and chronic unpredictable mild stress for 21 days.

[Progress in the study on the mechanism underlying the correlation between acupoints/meridians and Zangfu organs].

In the present paper, the authors review development of studies on the mechanism underlying the correlation between acupoints/ meridians and internal organs in recent 10 years from (1) doctrine of "dynamic acupoint"; (2) effect of one acupoint-stimulation on multi-viscera, (3) effect of multi-acupoints/multi-meridians stimulation on one single internal organ, (4) specific reactions of visceral disorders on the body surface, (5) the therapeutic effect of acupoint-injection being better than muscular injection, (6) effect of acupuncture on the expression of some known intracellular genes/proteins of the related viscera, (7) effect of acupuncture on the expression or phosphorylation of whole genes/whole proteins of the related viscera, (8) peripheral pathways connecting acupoints and the associated internal organ, (9) central pathways connecting acupoints and the related viscera, and (10) overview of the similar researches in foreign countries. In addition, the authors also make a preliminary analysis on the research significance, current problems and the thoughts in the coming studies. Utilizing advanced knowledge and techniques of systems biology to study "the correlation between acupoints/meridians and internal organs" will greatly promote the development of acupuncturology.

[Effect of electroacupuncture on hippocampal NO-cGMP signaling pathway in depression rats].

Objective: To observe the effect of electroacupuncture (EA) on hippocampal nitric oxide (NO)-cyclic guanosine 3,5-monophosphate (cGMP) signaling pathway in depression rats in order to explore the underlying mechanism of EA in improving depression.

Methods: Thirty male SD rats were equally randomized into control, model and EA groups. Depression model was established by using chronic unpredictable mild stress stimulation (forced ice-water swimming, electric shock, tail-clamping, etc.