Simultaneous determination of 11 active components in Lonicera japonica flowers and leaves at different development stages by HPLC-DAD / 中国中药杂志

This study aims to develop an HPLC-DAD method for simultaneous determination of 11 components(6 phenolic acids and 5 iridoids) in Lonicera japonica flowers(LjF) and leaves(LjL), and compare the content differences of LjF at different development stages, LjL at different maturity levels, and between LjF and LjL. One-way ANOVA, principal component analysis(PCA), and orthogonal partial least-squares discriminant analysis(OPLS-DA) were employed to compare the content of the 11 components. The content of total phenolic acids, total iridoid glycosides, and total 11 components in LjF showed an overall downward trend with the development of flowers. The content of total phenolic acids, total iridoid glycosides, and total 11 components in young leaves were higher than those in mature leaves. The results of PCA showed that the samples at different flowering stages had distinguishable differences in component content. The VIP value of OPLS-DA showed that isochlorogenic acid A, chlorogenic acid, and secologanic acid were the main differential components of LjF at different development stages or LjL with different maturity levels. LjF and LjL have certain similarities in chemical composition while significant differences in component content. The content of total phenolic acids in young leaves was significantly higher than that in LjF at various development stages. The content of total iridoid glycosides in young leaves was similar to that in LjF before white flower bud stage. The total content of 11 components in young leaves was significantly higher than that in LjF at green flower bud stage, before and during completely white flower bud stage. LjL have great potential for development. Follow-up research on the pharmacodynamic equivalence of LjF and LjL(especially young leaves) should be carried out to speed up the development and application of LjL.

FGFR4: a promising therapeutic target for liver cancer / 药学学报

Fibroblast growth factor receptor (FGFR), as a member of the receptor tyrosine kinase family, participates in a variety of biological processes by binding to ligand fibroblast growth factors (FGFs) and activating downstream signaling pathways, such as cell proliferation, migration, anti-apoptosis, angiogenesis, etc. FGFR gene amplification, missense mutations, oncogenic fusion are related to the occurrence and development of many cancers. FGFR has become an important potential target in cancer treatment. At present most of these studies focus on FGFR1-3, however there is growing evidence implicating an important and unique role of FGFR4 in oncogenesis and resistance to anti-tumor therapy in multiple types of cancer. The abnormality of FGF19-FGFR4 signaling pathway has been proved to be a carcinogenic factor of liver cancer. Importantly, there are several novel FGFR4-specific inhibitors in clinical trials, FGFR4 is therefore a promising target for the treatment of hepatocellular carcinoma harboring aberrant FGF19-FGFR4 signaling. In this review, we focus on assessing the role of FGFR4 in liver cancer, including a summary of the structure and ligand of FGFR4, downstream signaling pathways, abnormal activation in liver cancer, and the research progress of small molecule FGFR4 inhibitors, FGFR4 monoclonal antibodies and combined immunotherapy.

Positive inotropic effect of phosphodiesterase type 9 inhibitor PF-04449613 in rats and its underlying mechanism / 生理学报

This study aimed to explore the positive inotropic effect of phosphodiesterase type 9 (PDE9) inhibitor PF-04449613 in ratsand its cellular and molecular mechanisms. The heart pressure-volume loop (P-V loop) analysis was used to detect the effects of PF-04449613 on rat left ventricular pressure-volume relationship, aortic pressures and peripheral vessel resistance in healthy rats. The Langendorff perfusion of isolated rat heart was used to explore the effects of PF-04449613 on heart contractility. The cardiomyocyte sarcoplasmic reticulum (SR) Ca

Positive inotropic effect of Ivabradine in rats and its underlying mechanism / 医学研究生学报

ObjectiveIvabradine reduces heart rate by inhibiting If current of cardiomyocyte and is used clinically to treat stable angina pectoris and myocardial ischemia. However, the mechanism of positive inotropic effect by Ivabradine is still not well understood. This study aims to investigate the Ivabradine's positive inotropic effect both in vivo and in vitro and the underlying mechanism involved.Methods①A Millar catheter with double-pressure was inserted into the right carotid artery of general anesthesia rats. The pressure-volume of left ventricle, HR (heart rate) and aortic pressure were recorded as a blank group (n=7). The effect of Ivabradine (1 mg/kg) administrated via left external jugular vein was recorded as a drug treated group (n=7). The cardiac output, left ventricular and aortic pressure of the rats in the blank group A and the administration group A were compared, and the results were used to analyze the Ivabradine's inotropic effectin vivo.②Langendorff setup was used to analyze the left ventricular pressure of the isolated heart. The normal perfusion solution was used as the blank group (n=6), while the Ivabradine (10 μmol/L) perfusion was used as the treated group (n=6). In addition, the treatment of H89 (200 nmol/L) (a PKA inhibitor) was recorded as the blank group (n=6) and the combined use of H89 (200 nmol/L) and Ivabradine (10 μmol/L) was recorded as drug treated group (n=6). Following the above protocol, KN-93 (500 nmol/L) (a CaMKII inhibitor) or CA (10 nmol/L) (a protein phosphatase 1 and 2A inhibitor) was used to analyze the inhibitory effect on inotropic effect of Ivabradine (n=6 for each group). ③The field stimulation induced Ca2+ transient from cardiomyocyte was used to investigate the mechanism underlying the positive inotropic effect of Ivabradine (10 μmol/L).The perfusion orders and concentrations of Ivabradine or/and H89, KN-93 and CA were the same as that in isolated rat heart experiment (n= 6 for each group).Results① Ivabradine (1 mg/kg) significantly increased the left ventricular develop pressure (from 102.43±11.06 in blank group to 109.86±11.65 mmHg in ivabradine treated group, P<0.01, n=7) and cardiac output (from 33.72±1.96 in blank group to 36.27±2.22 mL/min in ivabradine treated group, P<0.01, n=7). It reduced the heart rate (from 348.56±10.02 in blank group to 324.17±11.33 beats/min in ivabradine treated group, P<0.01, n=7) and increased the systolic blood pressure (from 99.74±8.67 in blank group to 108.57±9.24 mmHg in Ivabradine treated group, P<0.01, n=7) without significant change in diastolic blood pressure. ② Ivabradine (1, 10 μmol/L) significantly increased the left ventricular developed pressure (LVDP) (P<0.05, n=6). The positive inotropic effect of Ivabradine was blocked by CaMKⅡ inhibitor of KN-93. ③ Ivabradine (10 μmol/L) significantly increased the amplitude of SR Ca2+ transient (P<0.01,n=6). The enhanced amplitude of Ca2+ transient was blocked by CaMKⅡ inhibitor of KN-93.ConclusionIvabradine shows a positive inotropic effect in rat hearts both in vivo and in vitro and its underlying mechanism involved the action which was mediated by CaMKⅡ.

H₂S protecting against lung injury following limb ischemia-reperfusion by alleviating inflammation and water transport abnormality in rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the effect of H₂S on lower limb ischemia-reperfusion (LIR) induced lung injury and explore the underlying mechanism.</p><p><b>METHODS</b>Wistar rats were randomly divided into control group, IR group, IR+ Sodium Hydrosulphide (NaHS) group and IR+ DL-propargylglycine (PPG) group. IR group as lung injury model induced by LIR were given 4 h reperfusion following 4 h ischemia of bilateral hindlimbs with rubber bands. NaHS (0.78 mg/kg) as exogenous H₂S donor and PPG (60 mg/kg) which can suppress endogenous H₂S production were administrated before LIR, respectively. The lungs were removed for histologic analysis, the determination of wet-to-dry weight ratios and the measurement of mRNA and protein levels of aquaporin-1 (AQP₁), aquaporin-5 (AQP₅) as indexes of water transport abnormality, and mRNA and protein levels of Toll-like receptor 4 (TLR₄), myeloid differentiation primary-response gene 88 (MyD88) and p-NF-κB as indexes of inflammation.</p><p><b>RESULTS</b>LIR induced lung injury was accompanied with upregulation of TLR₄-Myd88-NF-κB pathway and downregulation of AQP1/AQP₅. NaHS pre-treatment reduced lung injury with increasing AQP₁/AQP₅ expression and inhibition of TLR₄-Myd88-NF-κB pathway, but PPG adjusted AQP₁/AQP₅ and TLR4 pathway to the opposite side and exacerbated lung injury.</p><p><b>CONCLUSION</b>Endogenous H₂S, TLR₄-Myd88-NF-κB pathway and AQP₁/AQP₅ were involved in LIR induced lung injury. Increased H₂S would alleviate lung injury and the effect is at least partially depend on the adjustment of TLR₄-Myd88-NF-κB pathway and AQP₁/AQP₅ expression to reduce inflammatory reaction and lessen pulmonary edema.</p>

Comparison of atypical orofacial pain and temporomandibular disorders synovitis pain processing in the human brain using functional magnetic resonance imaging / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To compare the central nervous system processing of orofacial pain patients who might have atypical pain (group 1) after occlusal treatment with those patients who had synovitis pain of temporomandibular disorders (TMD) (group 2).</p><p><b>METHODS</b>Seven patients in each group were included in this study. Ten painless normal subjects (group 3) were employed as a control group. Functional magnetic resonance imaging (fMRI) was used to observe the activation of the brain evoked by clenching. The fMRI data were treated statistically as the result of each group.</p><p><b>RESULTS</b>The main active regions of three groups were different. The main active regions of the group 1 were bilateral thalamus and anterior cingulate cortex. The group 2 activated a quite different pain network, including postcentral gyrus, cingulate gyrus and prefrontal cortices.</p><p><b>CONCLUSIONS</b>The pain network is different between the two groups of pain patients and the pain network is more sensitive in atypical pain patients than in synovitis pain patients.</p>

Brain activities during maximum voluntary clenching with and without soft splint in patients with hemimasticatory spasms by functional magnetic resonance imaging / 中华口腔医学杂志

<p><b>OBJECTIVE</b>Functional magnetic resonance imaging (fMRI) was used to detect the cerebral cortical somatotopy during maximum voluntary clenching with and without soft splint in patients with hemimasticatory spasms (HMS) and the central mechanisms of HMS and the rule of the splint therapy.</p><p><b>METHODS</b>Four HMS patients were selected and the spasms sides were right in two cases and left in the other two cases. FMRI images were obtained on Elscint/GE 2.0 Tesla MR system. Block design was used and the movement pattern was the onset of spasms after maximum voluntary clenching with and without soft splint. The fMRI data were analyzed by SPM99 software.</p><p><b>RESULTS</b>With the onset of spasms after maximum voluntary clenching, the activation of motor cortex in 3 HMS patients was found lateral dominance on the left side, and the other one showed bilateral activation. All the 4 patients were found activation in cingulate area. With the onset of spasms after maximum clenching wearing soft splints, the activation of motor cortex showed no lateral dominance on the left side, and 3 patients were not found activation in cingulate area.</p><p><b>CONCLUSIONS</b>The changes of the activation in motor cortex and cingulate area during the onset of spasms after clenching with and without soft splint might be the central mechanisms of the rule of splint therapy, through which the soft splint might function in alleviating muscle pain.</p>

Brain activities during maximum voluntary clenching with soft occlusal pad in healthy adults by functional magnetic resonance imaging / 华西口腔医学杂志

<p><b>OBJECTIVE</b>Using functional magnetic resonance imaging (fMRI) to detect the cerebral cortical somatotopy during maximum voluntary clenching with soft occlusal pad in healthy adults. By comparing with the cerebral cortical activation during clenching with and without soft occlusal pad we try to detect the central mechanism of the rule of the occlusal pad.</p><p><b>METHODS</b>Ten healthy subjects were selected and scanned by Elscint/GE 2.0 Tesla MR system. Block design was used and the movement pattern was maximum voluntary clenching with soft occlusal pad. The fMRI data were analyzed by SPM99 software and group map analysis was done.</p><p><b>RESULTS</b>The activation areas were found in bilateral or unilateral motor cortex, somatosensory cortex, prefrontal cortex, temporal cortex, premotor cortex, insula, frontal operculum, basal ganglia (putamen), parietal cortex and cingulate. Group map analysis showed activation in bilateral motor cortex, right somatosensory cortex, bilateral basal ganglia, and bilateral insula. The activation of left motor cortex was significantly higher than right side. Compared with cortical activation without occlusal pad, the motor and somatosensory cortex changed a lot.</p><p><b>CONCLUSION</b>The changes of the activation of motor and somatosensory cortex during clenching after wearing the soft occlusal pad might be the central mechanism of the rule of the occlusal pad.</p>

Clinical Effect and Follow-Up Analysis of Transcatheter Occlusion Therapy on Patent Ductus Arteriosus in Infants / 实用儿科临床杂志

Objective To evaluate the clinical effect of transcatheter closure with Amplatzer duct occluder offers in infants with patent ductus arteriosus(PDA).Methods Thirty-seven PDA infants underwent transcatheter closure of PDA at(8.7 ? 3.3)months and weight of(8.6 ? 3.5)kg.A lateral view aortogram was made to determine the morphology and the narrowest diameter of the ductus and selected the size of the device.Occluder was implanted using the anterograde venous approach.Follow-up evaluations were made with chest X-ray and echocardiogram at 24 hours and 1,6 and 12 months after implantation.Results The narrowest diameter of the ducts measured by angiographically was(3.3 ? 1.5)mm.Ninteen patients(54.29%) achieved immediate complete occlusion.On color Doppler the closure rates at 1 month after implant were 34 cases(97.14%).No residual shunt exsisted in all implanted patients at 6 and 12 months follow-up.Procedure time at(57 ? 43)minutes and fluoroscopy time(23.0?14.9)minutes.Conclusions Percutaneous PDA closure with the Amplatzer duct occluder decice is an safety and effective method for the treatment of PDA in infants,but caution shall be exercised to the anatomic characteristics in the infant age group in solving clinical complications.

Hemimasticatory muscle spasm: an electromyogram analysis / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the usefulness of electromyogram (EMG) in the diagnosis of the patients with hemimasticatory spasm (HMS).</p><p><b>METHODS</b>Four cases with HMS were reported. All the 4 patients were undertaken needle and surface electrode EMG examination.</p><p><b>RESULTS</b>Needle electrode EMG of the 4 patients with HMS showed grouped potentials synchronously with the onset of the spasm, which indicated abnormal excitatory electrical activities of the trigeminal nerve resulting in involuntary masticatory muscle movements.</p><p><b>CONCLUSION</b>It is very important to use EMG for the diagnosis of HMS.</p>