Calcium/calmodulin-dependent protein kinase II is involved in the transmission and regulation of nociception in naïve and morphine-tolerant rat nucleus accumbens

Background@#Synaptic plasticity contributes to nociceptive signal transmission and modulation, with calcium/ calmodulin-dependent protein kinase II (CaMK II) playing a fundamental role in neural plasticity. This research was conducted to investigate the role of CaMK II in the transmission and regulation of nociceptive information within the nucleus accumbens (NAc) of naïve and morphine-tolerant rats. @*Methods@#Randall Selitto and hot-plate tests were utilized to measure the hindpaw withdrawal latencies (HWLs) in response to noxious mechanical and thermal stimuli. To induce chronic morphine tolerance, rats received intraperitoneal morphine injection twice per day for seven days. CaMK II expression and activity were assessed using western blotting. @*Results@#Intra-NAc microinjection of autocamtide-2-related inhibitory peptide (AIP) induced an increase in HWLs in naïve rats in response to noxious thermal and mechanical stimuli. Moreover, the expression of the phosphorylated CaMK II (p-CaMK II) was significantly decreased as determined by western blotting. Chronic intraperitoneal injection of morphine resulted in significant morphine tolerance in rats on Day 7, and an increase of p-CaMK II expression in NAc in morphine-tolerant rats was observed. Furthermore, intra-NAc administration of AIP elicited significant antinociceptive responses in morphine-tolerant rats. In addition, compared with naïve rats, AIP induced stronger thermal antinociceptive effects of the same dose in rats exhibiting morphine tolerance. @*Conclusions@#This study shows that CaMK II in the NAc is involved in the transmission and regulation of nociception in naïve and morphine-tolerant rats.

Diquafossol sodium combined with Qingrun Yangmu oral liquid for the treatment of dry eye after cataract operation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical efficacy of diquafosol sodium(DQS)eye drops combined with Qingrun Yangmu oral liquid in the treatment of dry eye after phacoemulsification and intraocular lens implantation.METHODS:A total of 57 patients(65 eyes)with dry eye after cataract surgery, who were admitted to the ophthalmology department of our hospital from September 2020 to January 2021, were selected as the research objects. They were divided into a control group(28 cases, 32 eyes, treated with 3% DQS eye drops)and an observation group(29 cases, 33 eyes, treated with 3% DQS eye drops combined with the Qingrun Yangmu oral liquid)based on a random number table method. Indicators, such as ocular surface disease index(OSDI), non-invasive tear film break-up time(NIBUT), Schirmer I test(SIt), corneal fluorescein sodium staining(CFS), and TCM symptom score, were compared and analyzed between the two groups 1d before, 1wk after(before treatment), and 1mo after(after treatment)surgery.RESULTS:The total effective rates of the observation group and the control group after treatment were 88% and 75%, respectively. The OSDI, NIBUT and SIt of the two groups after treatment showed significant improvement compared to those before treatment(P<0.05). The NIBUT, SIt, CFS, and TCM symptom scores of the observation group after treatment were better than those of the control group(P<0.05). No adverse reactions were observed in both groups.CONCLUSION:Combined use of DQS eye drops and the Qingrun Yangmu oral liquid can improve symptoms and clinical indicators of dry eye after cataract surgery, providing a new treatment method for ocular surface management of dry eye during the perioperative period of cataract surgery.

Effect of electroacupuncture on myocardial fibrosis in spontaneously hypertensive rats based on cholinergic anti-inflammatory pathway / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHR), and explore preliminarily the mediating role of cholinergic anti-inflammatory pathway (CAP) and its downstream nuclear factor κB (NF-κB) signaling pathway.@*METHODS@#Six 12-week-old WKY male rats were employed as the normal group. Eighteen 12-week-old SHR were randomly divided into 3 groups, i.e. a model group, an EA group and a blocking group (EA after blocking α7 nicotinic acetylcholine receptor [α7nAchR]), with 6 rats in each one. In the EA group, EA was delivered at "Neiguan"(PC 6) and the site 0.5 cm from its left side, with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity. One intervention took 30 min and was given once every 2 days, lasting 8 weeks. In the blocking group, prior to each EA, the α7nAchR specific blocker, α-bungartoxin was injected intravenously in the tails of the rats. After EA intervention, the systolic blood pressure (SBP), the diastolic blood pressure (DBP) and the mean arterial pressure (MAP) were measured with non-invasive blood pressure monitor. Using echocardiogram, the left ventricular (LV) anterior wall end-diastolic thickness (LVAWd) , LV posterior wall end-diastolic thickness (LVPWd) and the LV end-diastolic internal diameter (LVIDd) were measured. The level of hydroxyproline (Hyp) in the myocardial tissue was determined by using alkaline hydrolysis, and that of acetylcholine (Ach) was detected by ELISA. With the real-time PCR adopted, the mRNA expression of NF-κB p65, tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 were determined.@*RESULTS@#Compared with the normal group, SBP, DBP, MAP, LVAWd and LVPWd were increased (P<0.01), and LVIDd was decreased (P<0.01) in the rats of the model group. SBP, DBP, MAP and LVAWd were dropped (P<0.01, P<0.05), and LVIDd rose (P<0.01) in the EA group when compared with those in the model group. The differences in the above indexes were not statistically significant between the blocking group and the model group (P>0.05). Compared with the normal group, Hyp level and the mRNA expression of NF-κB p65, TNF-α, IL-1β and IL-6 in the myocardial tissue increased (P<0.01, P<0.05) and Ach level decreased (P<0.01) in the model group. Hyp level, the mRNA expression of NF-κB p65, TNF-α, IL-1β and IL-6 in the myocardial tissue were reduced (P<0.05, P<0.01) and Ach level rose (P<0.01) in the EA group when compared with those in the model group. These indexes were not different statistically between the blocking group and the model group (P>0.05).@*CONCLUSION@#CAP may be involved in ameliorating the pathological damage of myocardial fibrosis during EA at "Neiguan"(PC 6). The underlying effect mechanism is associated with up-regulating the neurotransmitter, Ach and down-regulating mRNA expression of NF-κB p65 and pro-inflammatory factors such as TNF-α, IL-1β and IL-6 in myocardial tissue.

Research progress on muscle spindle morphology / 生理学报

Muscle spindle is the key proprioceptor in skeletal muscles and plays important roles in many physiological activities, such as maintaining posture, regulating movement and controlling speed variation. It has significant clinical relevance and is emerging as a promising therapeutic target for the treatment of motor functional impairment and metabolic diseases. In this review, we summarized muscle spindle distribution and the mechanism of mechanical signal transmission, and reviewed the research progress on morphological and structural characteristics of muscle spindles.

New advances in vital pulp therapy and pulp regeneration for the treatment of pulpitis: from basic to clinical application / 中华口腔医学杂志

In recent years, great progress has been made in research on the treatment of pulpitis, mainly due to the rapid development of basic and clinical researches in this field, and some achievement from basic research has been applied in clinical practice. Advances in the diagnostic methods for pulpitis can help the clinicians to recognize the true state of pulpitis more accurately and to adopt the corresponding treatment methods including indirect/direct pulp capping, pulpotomy, pulp regeneration and root canal therapy. The new theory of pulpitis diagnosis and the studies on immune defense, repair function of dental pulp and new pulp capping materials have significantly improved the success rate of vital pulp therapy. For diffuse coronary pulpitis or radicular pulpitis, which is difficult to achieve vital pulp therapy successfully, methods of pulp revascularization, cell homing and pulp stem cells-mediated pulp regeneration can also be used as treatment options in addition to root canal therapy. The present article focuses on the research progress on pulpitis treatments and related clinical transformation practices, in order to provide reference on vital pulp therapy and pulp regeneration for clinicians.

Anatomical analysis of muscle spindles in tibialis anterior and extensor digitorum longus muscle of C57BL/6 mice / 解剖学报

Objective To locate the distribution of muscle spindles in tibialis anterior (TA) and extensor digitorum longus muscle (EDL) and the anchoring mode of muscle spindles in skeletal muscles, and perform statistics analysis of their morphological character by anatomical parameters. Methods Five adult wild type C57BL/6 mice were sacrificed, and TA and EDL were dissected and frozen with improved ultra-low temperature cryopreservation technology avoiding myofibers damaged by possible ice crystal. Continuous frozen transections were obtained and operated by HE staining, followed by microimaging to spot the muscle spindles location. Some parameters including regions length and cross section area (CSA) of muscle spindles were noticed for the discovery of some general characteristics of spindles by statistics. Results For TA and EDL, the scattered characters of muscle spindles were distributed as follows: the spindles were located at the upper third of the mid-belly of both TA and EDL from caudal to rostral position, while near the enter point to muscle of the deep peroneal nerve in dorsal-ventral orientation. The peripheral of muscle spindles anchored to extrafusal fibers to hold in the muscle. And in term of length, region A, connected with sensory nerve ending, demonstrated a significant correlation with region B, which located at the poles of region A and twined by motor nerve ending (correlation index = 0. 75) when considering the muscle spindles with four intrafusal fibers only. And no correlation was discovered in any others pairwise parameters. Conclusion The scattered diagram of muscle spindles in TA and EDL of C57BL/6 mice might provide anatomic basis for evaluation of lower limb motor function, especially for the spinal cord injury and recovery research. And the correlationship between the length of region A and B might improve exploring the variability of electrophysiological characters.

Dahuang zhechong pills regulate ASICla/VEGF pathway and alleviate hepatic fibrosis / 中国药理学通报

Aim To examine the therapeutic effects of DHZCP on carbon tetrachloride(CCl4)-induced chemical hepatic fibrosis model in rats and the mechanism of acid-sensitive ion channels 1a(ASIC1a)and vascular endothelial growth factor(VEGF)-related mechanisms.Methods The rats were injected intraperitoneally with CCl4 vegetable oil mixture to establish hepatic fibrosis model,and randomly divided into six groups:control group,hepatic fibrosis model group,DHZCP low dose group,DHZCP medium dose group,DHZCP high dose group and colchicine(Col)positive control group.HE staining was used to observe the pathological changes of hepatic structures in each group,Masson staining to view the production of collagen fibers in each group,and immunohistochemistry,Western blot,q-PCR to investigate the expression level of ASIC1a,CaMKKβ,VEGF,α-SMA,Collagen-I proteins.Results In model group,serum ALT and AST levels were obviously up-regulated,liver tissue structure was severely damaged,and ASIC1a,CaMKKβ,VEGF,α-SMA,Collagen-I gene and protein expression levels were significantly elevated.Compared with model group,each treatment group of DHZCP could markedly alleviate the pathological changes of liver fibrosis caused by CCl4,significantly reduce the serum ALT and AST levels,and dose-dependently down-regulate the gene and protein expression levels of ASIC1a,CaMKKβ,VEGF,α-SMA,Collagen-I,etc.Conclusions DHZCP ameliorates hepatic fibrosis in rats,and its mechanism of action may be associated with the regulation of ASIC1a/VEGF.

Preliminary study on mechanism of electroacupuncture with the involvement of SERCA2a/PLB on the synergistic and attenuated effect of aconitine in treatment of heart failure / 中国针灸

OBJECTIVE@#To investigate the mechanism of electroacupuncture (EA) with the involvement of sarcoplasmic reticulum Ca@*METHODS@#Thirty SPF-ranked SD rats were randomly divided into a control group, a model group, an EA group, an aconitine group and an EA plus aconitine group, with 6 rats in each group. The rat model of acute heart failure was established by infusion of high-dose propranolol hydrochloride solution into the right femoral vein. After stabilized for 10 min in the modeled rats, EA was exerted at "Neiguan" (PC 6), with disperse-dense wave, 2 Hz/15 Hz in frequency, 3 mA in intensity, for 30 min in the EA group and the EA plus aconitine group; aconitine solution (10 μg/kg) was injected from the left femoral veins in the rats in the aconitine group and the EA plus aconitine group. Hemodynamic indexes such as the left ventricular systolic pressure (LVSP) and the maximum rate of increase/decrease of left ventricular pressure (±dp/dt@*RESULTS@#Compared with the control group, LVSP and ±dp/dt@*CONCLUSION@#The intervention with electroacupuncture achieves the synergism/ attenuation effect of aconitine for the improvements in heart failure probably by up-regulating the expression of SERCA2a and down-regulating the expression of PLB in myocardial tissue.

Improving Effect of Modified Buyang Huanwutang Combined with Electroacupuncture on Traumatic Spinal Cord Injury due to Qi Deficiency and Blood Stasis / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Buyang Huanwutang combined with electroacupuncture （EA） in the treatment of traumatic spinal cord injury （TSCI） due to Qi deficiency and blood stasis. Method:Eighty-seven TSCI patients who met the inclusion requirements were randomly divided into an observation group （<italic>n</italic>=44） and a control group （<italic>n</italic>=43）. On the basis of comprehensive western medical treatments， patients in the control group were further provided with Wuwei Tongshuan oral liquid，10 mL per time，three times per day， while those in the observation group received modified Buyang Huanwutang，one bag per day，for 12 consecutive weeks. Besides， EA was performed in both groups in the same way， once per day， six times per week， for six weeks in total. The American Spinal Injury Association （ASIA） motor score， modified Barthel index （MBI），visual analog scale （VAS） pain score，Berg balance scale （BBS） score，modified Ashworth scale （MAS） score， spinal cord independence measure-Ⅲ（SCIM-Ⅲ） score， lower limb range of motion （ROM）， and Qi deficiency and blood stasis syndrome score before and after treatment were evaluated， followed by the recording of the occurrence of complications during treatment. The brain-derived nerve growth factor （BDNF）， nerve growth factor （NGF）， vascular endothelial growth factor （VEGF）， neurotrophic factor-3 （NT-3）， malondialdehyde （MDA） and superoxide dismutase （SOD） levels before and after treatment were determined. Result:The motor， light touch， needling sensation， MBI， and BBS scores of the observation group were higher than those of the control group （<italic>P</italic><0.01）， while the AS and MAS scores were lower（<italic>P</italic><0.01）. The angles of adductor and straight leg raising in the observation group were greater than those of the control group （<italic>P</italic><0.01），but the Qi deficiency and blood stasis syndrome score was lower（<italic>P</italic><0.01）. Both the scores of self-care， respiration， and sphincter management in SCIM-Ⅲ and the total score in the observation group were elevated as compared with those of the control group （<italic>P</italic><0.01）. The cumulative incidence of complications in the observation group was 34.09%，significantly lower than 55.81% in the control group （<italic>χ</italic>²=4.149，<italic>P</italic><0.05）. Compared with the control group， the observation group exhibited remarkably increased BDNF， NGF， VEGF， NT-3， and SOD （<italic>P</italic><0.01） and decreased MDA （<italic>P</italic><0.01）. Conclusion:Modified Buyang Huanwutang combined with EA is effective in alleviating spinal cord injury， promoting neural functional recovery， improving independence in activities of daily living， reducing the incidence of complications of patients with TSCI， which may be related to the amelioration of ischemia and hypoxia， inhibition of lipid peroxidation， and acceleration of nerve cell repair and regeneration.

Baicalin protects against 17α-ethinylestradiol-induced cholestasis via Sirt1/HNF-1α/FXR pathway / 中国药理学与毒理学杂志

OBJECTIVE Baicalin is a major flavonoid component of Scutellaria baicalensis, and has been used in the treatment of liver diseases for many years. However, the role of baicalin in estrogen-induced cholestasis (EIC) remains to be elucidated. This present study explored the protective effect of baicalin against estrogen-induced liver injury and further elucidated the mechanisms involved both in vivo and in vitro. METHODS We conducted a series of experiments using 17α-ethinylestradiol (EE) induced cholestatic rats and cultured HepG2 cells. Serum, bile, and liver samples were collected for biochemical and histological analyses. Bile acid composition in liver was analyzed by LC-MS/MS. The mechanisms underlying the hepatoprotective of baicalin were investigated by RT-PCR, Western blotting analyses and immunohistochemistry. RESULTS Baicalin showed obvious hepatoprotective effects in EIC rats by reducing serum bio?markers and increasing the bile flow rate, as well as by alleviating liver histology and restoring the abnormal composition of hepatic bile acids (BAs). In addition, baicalin protected against EE induced liver injury by up-regulation of the expres?sion of hepatic efflux transporters and down-regulation of hepatic uptake transporters. Furthermore, baicalin increased the expression of hepatic BA synthase (CYP27A1) and metabolic enzymes (Bal, Baat and Sult2a1) in EIC rats. We showed that baicalin significantly inhibited hepatic inflammatory responses in EIC rats through reducing elevated levels of TNF-α, IL-1β, IL-6 and NF-κB. Finally, we confirmed that baicalin maintains BA homeostasis and alleviates inflamma?tion through Sirt1/HNF-1α/FXR signaling pathway. CONCLUSION Baicalin protects against estrogen-induced cholestatic liver injury, and the underlying mechanism involved is related to activation of the Sirt1/HNF-1α/FXR signaling pathway.

Comparison of Effect of Chijian and Gastrodiae Rhizoma on Regulating Immune Function and Intestinal Microflora / 中国实验方剂学杂志

Objective:To compare the contents of adenosine， gastrodin， <italic>p</italic>-hydroxybenzyl alcohol， <italic>p</italic>-hydroxybenzaldehyde， parisinin B and parisinin A in Chijian （the aerial part of <italic>Gastrodia elata</italic>） and Gastrodiae Rhizoma， and compare their effects on immune function and intestinal microflora， evaluating whether it is necessary to study and develop Chijian. Method:The contents of these six constituents were determined by ultra performance liquid chromatography （UPLC）， the mobile phase was 0.1% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-4 min， 0.5%B； 4-5 min， 0.5%-2%B； 5-10 min， 2%-15%B； 10-12 min， 15%-20%B； 12-15 min， 20%-95%B； 15-17 min， 95%B； 17-17.5 min， 95%-0.5%B； 17.5-20 min， 0.5%B）， the flow rate was 0.5 mL·min^-1， the detection wavelength was 270 nm. The difference of pharmacological activity of water extracts of Chijian and Gastrodiae Rhizoma was compared， the clearance index， corrected clearance index and peripheral blood were measured in mice model with low immune function induced by cyclophosphamide， B lymphocyte proliferation was determined by lymphocyte transformation test <italic>in vitro</italic>， intestinal microflora was analyzed by 16S rDNA technology and bioinformatics was conducted. Result:The total contents of these six components in powder and ethanol extract of Chijian were higher than that of Gastrodiae Rhizoma， but the total contents of these six components in their water extract were similar， and the total contents of gastrodin and <italic>p</italic>-hydroxybenzyl alcohol met the requirements of the 2020 edition of <italic>Chinese Pharmacopoeia</italic>. Compared with the blank group， the clearance index of immunocompromised mice was significantly increased in the middle-dose （10 g·kg^-1） group of Chijian water extract， middle- and low-dose （10， 5 g·kg^-1） groups of Gastrodiae Rhizoma water extract （<italic>P</italic><0.05）， the levels of erythrocyte and hematocrit in peripheral blood were significantly increased in the high-dose （20 g·kg^-1） groups of water extracts of Chijian and Gastrodiae Rhizoma （<italic>P</italic><0.05， <italic>P</italic><0.01）， water extract of Gastrodiae Rhizoma with concentration of 400 g·L^-1 and the water extract of Chijian with the concentration of 100 g·L^-1 could promote the proliferation of B lymphocytes induced by lipopolysaccharide. Studies on intestinal microflora showed that compared with the blank group， at the phylum level， the water extracts of Chijian and Gastrodiae Rhizoma increased the relative abundance of Bacteroidetes and decreased the relative abundance of Firmicutes， at the genus level， they increased the relative abundance of <italic>Prevotellaceae</italic>_UCG-001 and <italic>Ruminococcaceae</italic>_UCG-005， and decreased the relative abundance of <italic>Anaerotruncus</italic>， unclassified_<italic>f</italic>_<italic>Erysipelotrichaceae</italic> and<italic> Candidatus</italic>_<italic>Stoquefichus</italic>.<italic> </italic>These intestinal bacteria were related to the immune system， cell proliferation， and metabolism regulation. Conclusion:The total contents of 6 components in the powder， the ethanol and the water extracts of Chijian are higher than or close to those of the corresponding samples of Gastrodiae Rhizoma， the pharmacological activity of Chijian water extract is similar to that of Gastrodiae Rhizoma water extract， indicating that Chijian is worthy of further research and development.

Lacrimal duct probing combined with tobramycin eye drops in the treatment of congenital dacryocystitis / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To explore the clinical efficacy of probing lacrimal passage combined with tobramycin eye drops in the treatment of congenital dacryocystitis. <p>METHODS: A total of 228 children(250 eyes)aged from 6mo-3a with congenital dacryocystitis treated in our hospital from January 2017 to June 2019 were included. They were assigned into three groups by age: 133 patients(149 eyes)aged from 6mo-1a(Group A), 62 patients(64 eyes)aged from 1-2a(Group B), and 33 patients(37 eyes)aged from 2-3a(Group C). All patients received lacrimal duct probing in surface anesthesia combined with postoperative tobramycin eye drops. <p>RESULTS: The probing cure rates of congenital dacryocystitis among there groups were 97.3%(Group A), 92.2%(Group B)and 83.8%(Group C), respectively. No adverse events reported. Through comparison of these three groups, the cure rate of children from 6mo-1a was the highest. The difference was statistically significant(<i>P</i>=0.009).<p>CONCLUSION: Lacrimal duct probing is effective in the treatment of congenital dacryocystitis, and it is safe and reliable to combine tobramycin eye drops(TOBREX)after surgery. The best time for treatment is 6mo-1a. The operation is simple, less complication, with high clinical value.

Biphasic dissolution test and its application in the evaluation of poorly soluble drug preparations / 药学学报

Biphasic dissolution test, consisting of immiscible aqueous and organic phase, is an in vitro dissolution method that simultaneously measures the dissolution and partition of drugs. Due to the advantages of simulating in vivo absorption and overcoming the influence of surfactants on dissolution, it has been widely used to evaluate the poorly soluble drugs in vitro dissolution. Based on the relevant research in this field in recent years, this review summarizes the history, dissolution device, theoretical model and application of the biphasic dissolution test. Finally, the prospects in the development of biphasic dissolution test are also outlined.

Effect of Petroleum Ether Extract of Rhizoma Amorphophalli on Biological Characteristics of K562 Cells and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the role of petroleum ether extract of Rhizoma Amorphophalli (SLG) in inhibiting proliferation and promoting apoptosis and differentiation of leukemia K562 cells.@*METHODS@#K562 cells were processed by SLG and PD98059 which was the ERK signaling pathway blocker. Then cell vitality was tested by MTT. Cell apoptosis rate and positive percentage of antigen expression related with differentiation were detected by flow cytometry. The protein expression levels of ERK1/2 and pERK1/2 were detected by Western blot.@*RESULTS@#The proliferation activity of K562 was reduced by 50, 100, 200 mg/L SLG in a concentration dependent manner (r=0.9997). The apoptosis rate and positive expression rate of CD11b, CD14 and CD42b which were related with differentiation were raised by SLG, as well as the expression of pERK1/2, while PD98059 could reverse the promoting effect of SLG on apoptosis and differentiation partially.@*CONCLUSION@#SLG can inhibit the proliferation and promote apoptosis and differentiation of K562 cells through ERK signaling pathway.

Effects of Three Needling Manipulations of Zusanli (ST 36) on Deqi Sensations and Surface Myoelectricity in Healthy Participants / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of different acupuncture manipulations on Deqi sensations and surface myoelectricity, and explore the correlation between Deqi sensations and needling manipulations.@*METHODS@#Forty-five healthy participants accepted twirling, lifting-thrusting, and twirling plus lifting-thrusting manipulanions at right Zusanli (ST 36), respectively. The acupuncturist's and participants' Deqi sensations were collected by MGH Acupuncture Sensation Scale (MASS). The intensity and occurrence rate of soreness, dull pain, pressure, heaviness, fullness, numbness, sharp pain, warmth, coolness, and throbbing feelings of participants, and tightness, smooth, and tangle feelings of acupuncturist were measured. The correlation between the acupuncturist's and participant's Deqi sensations was analyzed. Surface electromyogram (EMG) were recorded before, during and after needling in 30 participants. The integrated EMG (iEMG), mean power frequency (MPF) and media frequency (MF) were analyzed.@*RESULT@#Both fullness and soreness of participants and tightness of acupuncturist were the most frequently occurred ones. A positive correlation between participants' fullness and acupuncturist's tightness was observed during the three aforementioned needling manipulations (P1). Almost all the needling sensations measured in the present study could be induced by the three needling manipulations. However, strength of Deqi sensations was exhibited as lifting-thrusting > twirling plus lifting-thrusting > twirling according to MASS index. The iEMG values were increased and MPF, MF values were decreased during needling compaired to those before needling, especially during lifting-thrusting (P<0.01).@*CONCLUSIONS@#The intensity and occurrence rate of the different Deqi sensations induced by different needling manipulations were basically similar. The fullness and soreness were both the most frequently induced Deqi sensations. The strongest Deqi sensation could be induced by lifting-thrusting manipulation. There is a positive correlation between participants' fullness and acupuncturist's tightness during the three needling manipulations. The myoelectricity around the acupoint is related to Deqi responses. (Registration No. AMCTR-IOR-20000314).

Effect of Panax Notoginseng Saponins on Breast Cancer Cell Line 4T1 in Tumor-bearing Mice Through MEKK1/SEK1/JNK1/AP-1 Pathway / 中国实验方剂学杂志

Objective:To explore the potential mechanisms of Panax Notoginseng Saponins （PNS） on growth inhibition of breast cancer cell line 4T1 in tumor-bearing mice by investigating the mitogen-activated protein kinase kinase kinase 1 （MEKK1）/stress activated protein kinase （SAPK）/extracellular regulated protein kinases （Erk） Kinase （SEK1）/c-Jun N-terminal kinase 1 （JNK1）/activator protein-1 （AP-1） signaling pathways. Method:The 4T1 breast cancer mice model was established. Forty-eight mice with successful modeled and randomly divided into the low， medium and high-dose PNS groups （10， 20， 40 mg·kg-1） and the model control group （12 mice in each group）. The PNS groups received intraperitoneal injection with dosage of 10 mL·kg-1， while the controlled group was given the same dosage of saline. After administration with PNS for 28 days， tumor tissues were isolated， weighed， sliced and homogenized. Tumor cell apoptosis was detected by TdT mediated-dUTP nick end labeling （TUNEL） staining. The mRNA expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissue were detected by Real-time polymerase chain reaction（Real-time PCR）. The protein expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissue were detected by immunofluorescence staining and Western blot. Result:Compared with model group， the tumor weights of medium-dose and high-dose PNS groups were decreased significantly （P<0.05）. TUNEL staining showed that the number of apoptotic tumor cells increased with the rise of dosage of PNS （P<0.05）. The medium-dose and high-dose PNS groups showed a significant increase in the mRNA expressions of MEKK1， SEK1， JNK1 and AP-1 as well as the protein expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissues （P<0.05）， with statistically significant differences （P<0.05）. Conclusion:PNS could inhibit the tumor growth of breast cancer cell line 4T1 in tumor-bearing mice， which may be related to the activation of MEKK1/SEK1/JNK1/AP-1 signaling pathways.

Progress in Research on Chemical Constituents and Quality Control METHODS: of Calculus Bovis and Its Substitutes / 中国药学杂志

Calculus Bovis is one precious traditional Chinese medicine used widely in clinical practice. Because of its high price and lack of resources, the substitutes of Calculus Bovis artificial Calculus Bovis, in vivo cultured Calculus Bovis and in vitro cultured Calculus Bovis also have been widely used in clinical practice. In order to understand the difference in chemical composition between Calculus Bovis and its substitutes, and determine whether all kinds of Calculus Bovis medicinal materials have special detection METHODS:, the chemical constituents and quality control METHODS: of Calculus Bovis and its substitutes were reviewed in this paper. Through the review of literature it was found that artificial Calculus Bovis mainly contain hyodeoxycholic acid and only a small amount of free bilirubin, and the chemical components of the other three kinds of Calculus Bovis medicinal materials are different. The chemical compositions of natural Calculus Bovis and in vitro cultured Calculus Bovis are similar, but the proportions of different types of bilirubin are different. At present, no characteristic ingredients of natural Calculus Bovis have been found to distinguish it from in vitro cultured Calculus Bovis and in vivo cultured Calculus Bovis.

Clinical value of IL-6 combined with CA125 and HE4 in the diagnosis of early ovarian cancer / 国际检验医学杂志

Objective To discuss the clinical value of IL-6 combined with CA125 and HE4 as a new association marker in the diagnosis of early ovarian cancer.Methods The expression of IL-6, CA125 and HE4 in 21 cases of early ovarian cancer (stageⅠ-Ⅱ), 36 cases of advanced ovarian cancer (stageⅢ-Ⅳ), 40 cases of benign ovarian tumor and 40 healthy women were measured by the Roche automatic chemiluminescence analyzer (electrochemiluminescence).The sensitⅣity, specificity, positive predictive value, negative predictive value and ROC curves were used to evaluate the diagnostic value.Results The serum levels of IL-6, CA125 and HE4 in patients with ovarian cancer were significantly higher than those in the benign ovarian tumor and the healthy control (P＜0.05).The sensitⅣity, specificity, positive predictive value and negative predictive value of IL-6 combined with CA125 and HE4 were respectively 85.7％, 90％, 81.8％, 92.3％in the diagnosis of early ovarian cancer (stageⅠ-Ⅱ) patients and respectively 94.4％, 97.5％, 97.1％and 95.1％for advanced ovarian cancer (stageⅢ-Ⅳ) patients.For IL-6 combined with CA125 and HE4, the ROC AUC was respectively 0.955 4 and 0.974 0 for early ovarian cancer (stageⅠ-Ⅱ) patients and advanced ovarian cancer (stageⅢ-Ⅳ) patients.It performed significantly better than any single test of IL-6, CA125 and HE4 and the 2-marker combination of CA125+HE4.Conclusion The marker panel, IL-6, CA125 and HE4, shows higher sensitⅣity, positive predictive value and ROC AUC.It is an ideal serum marker combination for the diagnosis of early ovarian cancer (stageⅠ-Ⅱ) patients, which can improve the diagnostic efficiency of early ovarian cancer.

Mechanism of Calculus Bovis Sativus in inhibiting hepatocyte lipid deposition based on serum pharmacology / 中国中药杂志

The aim of this paper was to investigate the molecular mechanism of Calculus Bovis Sativus( CBS) in alleviating lipid accumulation in vitro by serum pharmacology. The CBS-containing serum of mice was obtained by serum pharmacology method to evaluate its effect on the proliferation of LO2 hepatocytes. The lipid reducing effects of CBS-containing serum through Nrf2 was evaluated by fructose-induced LO2 hepatocyte steatosis model,nuclear factor erythroid 2 related factor 2( Nrf2) agonist oltipraz combined intervention,cell oil red O staining and intracellular triglyceride( TG) content. The effects of CBS-containing serum on lipid peroxidation and hepatocytes apoptosis were evaluated by reactive oxygen species( ROS) and apoptosis assay,respectively. Real-time quantitative polymerase chain reaction( PCR) was used to detect the relative expression of lipid synthesis-related genes and apoptosis-related genes.RESULTS:: showed that CBS drug-containing serum had no significant effect on LO2 hepatocyte proliferation. As compared with the model group,CBS-containing serum could effectively reduce the formation of lipid droplets in fructose-induced LO2 hepatocytes,significantly reduce intracellular TG and ROS levels,and significantly reduce hepatocyte apoptosis rate( P < 0. 05). As compared with the model group,carbohydrate responsive element binding protein( ChREBP),sterol regulatory element binding protein-1 c( SREBP-1 c),fatty acid synthase( FAS),acetyl-CoA carboxylase 1( ACC1),stearoyl-CoA desaturase 1( SCD1),Bax and caspase-3 mRNA levels were significantly reduced in CBS drug-containing serum treatment group( P<0. 05). All of the above effects could be reversed by oltipraz.In conclusion,CBS-containing serum can significantly inhibit the fructose-induced LO2 liver fat deposition,and the mechanism may be related to reducing intracellular ROS level through the Nrf2 pathway and improving intracellular peroxidation state to reduce apoptosis.

Research progress in pharmacological effects and pharmacokinetics of ginsenoside Rc / 中草药

Ginsenoside Rc is widely distributed in Araliaceae plants, especially in whole plant of Panax ginseng, roots of Panax quinquefolium, and flowers of Panax pseudoginseng var. notoginseng. And studies have shown that ginsenoside Rc has remarkable effects in anti-inflammatory, anti-oxidation, antitumor, lipid-lowering activities, prevention of diabetes, and protection of the nervous system. In this paper, the pharmacological effects and pharmacokinetics of ginsenoside Rc were reviewed in order to provide references for the development and application of drugs with rich ginsenoside Rc.