Clinical Efficacy and Mechanism of Xiao Qinglongtang in Treating Chronic Heart Failure with Cold Phlegm in Lung / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Xiao Qinglongtang on chronic heart failure with cold phlegm in lung， and explore its mechanism of action. Method:A total of 87 patients with definite chronic heart failure were divided into observation group and control group by random number table method．The two groups received routine western medicine at the same time. Forty-two cases in observation group were treated with Xiao Qinglongtang based on western medicine， and 45 cases in control group received the same dose of placebo. Both groups were treated for 4 weeks， and then their cardiac function， traditional Chinese medicine （TCM） syndrome score and efficacy were compared before and after treatment. Left ventricular ejection fraction （LVEF） and N-terminal pro-brain natriuretic peptide （NT-proBNP） were measured in both groups before and after treatment. The changes of standard deviation of NN intervals （SDNN）， square root of the mean squared differences of successive NN intervals （RMSSD）， high frequency （HF） and low frequency （LF） that reflect autonomic nerve function indexes in heart rate variability （HRV） after treatment were compared between two groups. The changes of inflammatory indicators such as interleukin-6 （IL-6） and highly sensitive C reaction protein （hs-CRP） were detected. Result:After treatment， the total effective rate for cardiac function in observation group was higher than that in control group （P<0.05）. The TCM symptom scores were improved after treatment in both groups （P<0.05）， and the total effective rate in observation group was higher than that in control group （P<0.01）. After treatment， LVEF levels significantly increased （P<0.01） and NT-proBNP levels significantly decreased （P<0.01） in both groups， and the effect in observation group was more obvious （P<0.01）. After treatment， SDNN， RMSD， HF and LF indicators in HRV were all higher than those before treatment in both groups （P<0.01）， and the improvement in observation group was more significant than that in control group （P<0.01）. The levels of IL-6 and hs-CRP decreased after treatment in both groups （P<0.01）， and the level of observation group was significantly lower than that of control group （P<0.01）. Conclusion:Xiao Qinglongtang has certain clinical efficacy in treating chronic heart failure with cold phlegm in lung as it can improve the clinical symptoms of patients， regulate autonomic nervous balance， and inhibit inflammatory factors， providing new clinical ideas to treat chronic heart failure in TCM.

Analysis of Forensic Sciences Literature in SCIE from 2008 to 2017 / 法医学杂志

OBJECTIVES@#To analyze the literature on forensic sciences indexed in Science Citation Index Expanded （SCIE） in recent 10 years, and to understand the research status, characteristics and trends in the field of forensic sciences.@*METHODS@#Literature on forensic sciences from 2008 to 2017 in Web of Science （WoS） was retrieved. The documents number and geographical distribution, document types, source titles, organizations, research areas, authors, funding agencies, and the high cited articles were detected. The impact factors （IF） of journals were retrieved in Journal Citation Reports （JCR）. The data were analyzed with descriptive statistics.@*RESULTS@#From 2008 to 2017, there were 21 001 documents on forensic sciences in SCIE. The main document type was articles, with English as the major language. With regards to research areas, pathology has the largest number of papers worldwide, and genetics and heredity has the largest number of publications in mainland China. Among the 18 journals where the documents was published, Forensic Science International ranks the first on publication count, and Forensic Science International Genetics has the highest IF （5.637） in the JCR 2017. In 2017, the number of papers from mainland China increased by 48.50% compared with 2016, which was higher than the global increase （32.63%） and the top-5 countries in terms of number of publications （the US, Germany, the UK, Australia, Italy）. The average document count per organization is 1.98 worldwide and 1.17 in mainland China, respectively. The publication number per author is 0.53 worldwide and 0.36 in mainland China, respectively. Around 28.17% of the publications were funded, with National Natural Science Foundation of China （NSFC） as the Top 1 funding agency （192 papers）. Among the documents with citations, the most cited publication has been cited for 366 times.@*CONCLUSIONS@#The yearly numbers of publications on forensic sciences are increasing during recent 10 years. Focusing on the mainland China, there would be more high-quality papers with the steady funding of NSFC.

Construction and implementation of a new system for fundamentals and frontiers of brain science curriculum for medical graduates / 医学研究生学报

In order to adapt to the rapid development of brain science and cultivate high-level innovative brain science research talents, combined with the practical teaching experience in the Department of Neurobiology of Air Force Military Medical University in recent years, the article constructs a new system for fundamentals and frontiers of brain science curriculum, which integrates advanced teaching concepts, diverse teaching forms and flexible teaching modes, expecting this new curriculum system will lay a solid foundation for the cultivation of talents in brain science.

Spinal CCL2 Promotes Central Sensitization, Long-Term Potentiation, and Inflammatory Pain via CCR2: Further Insights into Molecular, Synaptic, and Cellular Mechanisms / 神经科学通报·英文版

Mounting evidence supports an important role of chemokines, produced by spinal cord astrocytes, in promoting central sensitization and chronic pain. In particular, CCL2 (C-C motif chemokine ligand 2) has been shown to enhance N-methyl-D-aspartate (NMDA)-induced currents in spinal outer lamina II (IIo) neurons. However, the exact molecular, synaptic, and cellular mechanisms by which CCL2 modulates central sensitization are still unclear. We found that spinal injection of the CCR2 antagonist RS504393 attenuated CCL2- and inflammation-induced hyperalgesia. Single-cell RT-PCR revealed CCR2 expression in excitatory vesicular glutamate transporter subtype 2-positive (VGLUT2) neurons. CCL2 increased NMDA-induced currents in CCR2/VGLUT2 neurons in lamina IIo; it also enhanced the synaptic NMDA currents evoked by dorsal root stimulation; and furthermore, it increased the total and synaptic NMDA currents in somatostatin-expressing excitatory neurons. Finally, intrathecal RS504393 reversed the long-term potentiation evoked in the spinal cord by C-fiber stimulation. Our findings suggest that CCL2 directly modulates synaptic plasticity in CCR2-expressing excitatory neurons in spinal lamina IIo, and this underlies the generation of central sensitization in pathological pain.

Zhuanggu Jianxi Decoction () limits interleukin-1 β-induced degeneration chondrocytes via the caveolin-p38 MAPK signal pathway / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of Zhuanggu Jianxi Decoction (, ZGJXD) on interleukin-1 β (IL-1 β)-induced degeneration of chondrocytes (CDs) as well as the activation of caveolin-p38 mitogen-activated protein kinase (MAPK) signal pathway, investigating the possible molecular mechanism that ZGJXD treats osteoarthritis.</p><p><b>METHODS</b>Serum pharmacology was applied in the present study, where ZGJXD was orally administrated to New Zealand rabbits and then ZGJXD containing serum (ZGJXD-S) was collected for following in vitro experiments. CDs were isolated aseptically from New Zealand rabbits and then cultured in vitro. Upon IL-1 β stimulation, the degeneration of CDs was verified by inverted microscope, toluidine blue stain and type II collagen immunocytochemistry. After IL-1 β-stimulated CDs were intervened with blank control serum, ZGJXD-S, together with or without SB203580 (a specific inhibitor of p38 MAPK) for 48 h, caveolin-1 protein expression and the phosphorylation level of p38 were determined by Western blotting, and the mRNA expression of IL-1 β, tumor necrosis factor α (TNF-α), matrix metalloproteinase 3 (MMP-3) and MMP-13 were examined by real-time polymerase chain reaction.</p><p><b>RESULTS</b>IL-1 β stimulation induced degeneration of CDs, increased caveolin-1 expression and p38 phosphorylation, up-regulated the mRNA level of IL-1 β, TNF-α, MMP-3 and MMP-13. However, the IL-1 β-induced activation of caveolin-p38 signaling and alteration in the expression of p38 downstream target genes were suppressed by ZGJXD-S and/or SB203580 in CDs.</p><p><b>CONCLUSION</b>ZGJXD can prevent CDs degeneration via inhibition of caveolin-p38 MAPK signal pathway, which might be one of the mechanisms that ZGJXD treats osteoarthritis.</p>

Effect of naringin of Drynaria Rhizome, a Chinese medical component of Zhuanggu Jianxi Recipe containing serum on caveolin-p38MAPK signal pathway in IL-1β induced rabbit degenerated chondrocytes / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of naringin of Drynaria Rhizome, a Chinese medical component of Zhuanggu Jianxi Recipe (ZJR) containing serum on caveolin-p38MAPK signal factors (such as caveolin-1, p-p38, p-ATF-2, IL-1β, and TNF-α) in IL-1β induced rabbit degenerated chondrocytes, and further to explore its mechanism for protecting articular cartilages.</p><p><b>METHODS</b>Naringin of Drynaria Rhizome was obtained and analyzed by HPLC-TOF/MS. Four weeks old New Zealand rabbits were killed and their bilateral knee joints were isolated aseptically. CDs were isolated and then cultured in vitro. The second generation of CDs were used for later experiment. The effect of naringin on CDs proliferation was detected by MTT assay. The effect of naringin on the expression of IL-1β-induced collagen II in CDs was detected by immunohistochemical method. The effect of naringin on caveolin-1, p-p38, and p-ATF-2 protein in IL-1β-induced CDs was detected by Western blot. The effect of naringin on mRNA expression of IL-1β and TNF-α in IL-1β-induced CDs was detected by RT-PCR.</p><p><b>RESULTS</b>The appearance time of naringin in flow graphs of naringin standard solution and ZJR containing serum was 23.5 min, and the molecular weight ranged between 581.0 and 581.5 m/z. Naringin could promote the proliferation of CDs, and inhibit the effect of IL-1β on collagen II in CDs. Compared with the model group, naringin could reduce the expression of caveolin-1, p-p38, p-ATF-2, IL-1β, and TNF-α in IL-1β induced CDs (P < 0.05), which was approximate to the level of the normal group.</p><p><b>CONCLUSIONS</b>Naringin could not only promote the proliferation of CDs, but also protect IL-1β-induced CDs. Its mechanism might be associated with decreasing the expression of caveolin-1, p-p38, and p-ATF-2 proteins, inhibiting caveolin-p38MAPK signal pathway, and further reducing mRNA expression of IL-1β and TNF-α in the downstream of caveolin-p38MAPK signal pathway.</p>

Experimental study on the recycling of denatured acellular dermal matrix after burn / 中华烧伤杂志

<p><b>OBJECTIVE</b>To explore the feasibility of burn denatured acellular dermal matrix (DADM) as dermal substitute in repairing wounds.</p><p><b>METHODS</b>(1) Nine Wistar rats received a deep partial-thickness scald on the back. Full-thickness wounded skin was collected on post scald day (PBD) 1, 2, and 3 (with 3 rats at each time point), and it was treated with 2.5 g/L trypsin/0.5% Triton X-100 to remove cells to prepare DADM, respectively called DADM-1 d, DADM-2 d, and DADM-3 d. Another 3 rats without scald injury were treated with the same method as above to prepare acellular dermal matrix (ADM) to serve as control. Gross and histological observations and microbiological and biomechanical tests, including ultimate tensile strength, maximum tension, stretched length at breaking, stress-strain relationship, were conducted for the resulting ADM and DADM. (2) Another 64 rats were divided into ADM group and DADM-1 d, DADM-2 d, and DADM-3 d groups according to the random number table, with 16 rats in each group. A skin flap in size of 2.0 cm×1.8 cm was raised on the back of each rat. The above-mentioned ADM, DADM-1 d, DADM-2 d, and DADM-3 d were cut into pieces in the size of 1.8 cm×1.5 cm, and they were respectively implanted under the skin flaps of rats in corresponding group. At post surgery week (PSW) 1, 3, 5, or 9, 4 rats in each group were used to observe wound healing condition and change in implants with naked eye, and histological observation of the implants was conducted. Data were processed with one-way analysis of variance and t test.</p><p><b>RESULTS</b>(1) The freshly prepared DADM was milky white, soft in texture with flexibility, but poor in elasticity as compared with ADM. No epithelial structure or cellular component was observed in ADM or DADM under light microscope. Collagen fibers of DADM were seen to be thickened unevenly and arranged in disorder and eosinophilic. All microbiological results of DADM were negative. There was no statistically significant difference among DADM-1 d, DADM-2 d, and DADM-3 d in levels of ultimate tensile strength, maximum tension, stretched length at breaking, and stress-strain relationship (with F values from 0.088 to 3.591, P values all above 0.05). Values of the above-mentioned four indexes were the highest in DADM-3 d, they were respectively (13.0 ± 2.4) MPa, (61 ± 4) N, (173 ± 7)%, (45.7 ± 2.0)%. Values of the four indexes of ADM were respectively (19.0 ± 2.6) MPa, (95 ± 4) N, (201 ± 5)%, (62.5 ± 2.2)%, which were higher than those of DADM-1 d, DADM-2 d, and DADM-3 d (with t values from 6.424 to 17.125, P values all below 0.01). (2) No exudate or swelling in the wounds of rats, and no contraction or curling of implants were observed in every group at PSW 1, but inflammatory cells infiltration and Fbs inward migration were observed in the wound. At PSW 3, the growth of hair was normal in the wound in DADM-1 d, DADM-2 d, and ADM groups, but few and scattered hair grew in DADM-3 d group. The inflammatory cells decreased, while Fbs increased, and new capillaries were found to grow inwardly in each group. The decrease in inflammatory cells was slightly delayed in DADM-3 d group. At PSW 5, hair growth became normal, and implants shrank and thinned with fiber membrane wrapped densely and bundles of ingrowing large caliber blood vessels in all groups. The dermal matrix in each group merged with the surrounding normal tissue. At PSW 9, ADM and DADM became white, thin, and soft tissue sheet which was closely connected with the inner side of the flap. There was no infiltration of inflammatory cells in implants in either group. The collagen fibers arranged regularly and densely, and they were integrated with normal collagen tissue.</p><p><b>CONCLUSIONS</b>The burned DADM does not have obvious immunogenicity, but with good biocompatibility. It is prospective to become as a dermal substitute in repairing wounds.</p>

Bilateral anterior dorsal hippocampal network seizures induced by acute tetanization of the right posterior dorsal hippocampus / 中国应用生理学杂志

<p><b>AIM</b>To investigate the neural network and cellular mechanisms of hippocampal epileptogenesis contralateral or ipsilateral to the side of acute tetanization (60 Hz, 2 s, 0.4 - 0.6 mA) of the posterior dorsal hippocampus (ATPDH).</p><p><b>METHODS</b>10 trains of the ATPDH were administered into the CA1 basal dendritic region of the right hemisphere at an interval of 10 minutes.</p><p><b>RESULTS</b>(1) The firing rate of CA1 single neuron in the right or the left hippocampus was inhibited respectively after the ATPDH, and the effects weakened gradually while the trains of the ATPDH increased. The inhibited firing rate and the transformed firing pattern from tonic one to clonic one were more obvious at the side contralateral to the stimulation (62.94% +/- 3.68%, 36.61% +/- 3.14%, P < 0.01). (2) Synchronous primary afterdischarges of depth EEG and single unit discharges were more commonly observed at the side ipsilateral to the ATPDH (P < 0.01). (3) Primary or secondary hippocampal network afterdischarges at high frequency were only found in CA1 region ipsilateral to the ATPDH. (4) Secondary afterdischarges of CA3 basal dendritic neural network were completely synchronized with those of subicular single neuron, which reoccurred and persisted several hours.</p><p><b>CONCLUSION</b>It is possible that post-inhibition bursting of single neuron and recurrent network seizures in the hippocampus contralateral to the artificial focus be the important manifestation of the formation of "epileptic networks" across from one hemisphere to another.</p>

Propagation of brain injuries from artificial focus into the opposite hemisphere at the early stage of rat electrogenic epilepsy identified by histology and magnetic resonance image / 生理学报

The purpose of this work was to study the characteristics of rat brain abnormalities at two hemispheres at the early stage of electrogenic epilepsy. Experiments were performed on 37 male Sprague-Dawley rats. Chronically repetitive tetanization (60 Hz, 2 s, 0.4 - 0.6 mA) was used to stimulate the right dorsal hippocampus (DHPC) of the rat brain once a day for 2, 4, 6, 8 or 10 d, respectively. The T(2) weighted magnetic resonance image (T(2)-WI) were obtained from each experimental rat at the end of the experiments. Histological sections were obtained after experimentation. The results showed that the main pathologic changes at the early stage of epilepsy included: (1) T(2)-WI hyperintensification, the histological enlargement of lateral ventricle (LV) and pathological hyperplasia of ventricular choroidea plexus occurred. The pathological hyperplasia was symmetric in two hemispheres, but the LV enlargement was not. (2) Histologically enlarged LV area showed a resemblance to T(2)-WI hyperintensive area. Compared with the control rats, large T(2)-WI hyperintensive area (P=0.0259; P=0.0184; P=0.0184; P=0.0404; P=0.0259) and histologically enlarged LV area (P=0.0210; P=0.01; P=0.0100; P=0.0152) were present in chronically tetanized rats. (3) Dynamic characteristics of histologically enlarged LV area resembled to those of T(2)-WI hyperintensity area in chronically tetanized rats at different stimulating day. Lateralization of T(2)-WI hyperintensity was in accordance with that of T(2)-WI abnormal area and of histologically enlarged LV. These abnormalities were severe on the contralateral side on the stimulating day 6, or on the ipsilateral side on the stimulating day 10. These results imply characteristic propagation of brain abnormalities crossing to the opposite hemisphere at the early stage of an electrogenic rat epilepsy.

Epileptiform activity of the anterior dorsal hippocampal network induced by acute tetanization of the right posterior dorsal hippocampus of the rat / 生理学报

The purpose of the present work was to study the role of unilateral hippocampal neural network in hippocampal epileptogenesis and its cellular mechanisms. Experiments were performed on 45 Sprague-Dawley adult rats. Acute tetanization (60 Hz, 2 s, 0.4 - 0.6 mA) of the right posterior dorsal hippocampus (ATPDH) was used to induce hippocampal epilepsy. The single unit discharges and the depth electrographs were synchronously recorded with a glass microelectrode and a pair of stainless concentric electrodes in the ipsilateral anterior dorsal hippocampus (HPC). The results demonstrated that: (1) some primary unit after-discharges were synchronized with electrographic after-discharges in the anterior dorsal HPC network after eight or nine tetanic trains were administered. Others desynchronized with 5 - 90 Hz primary depth electrographic after-discharges; (2) primary electrographic after-discharges were driven by primary unit after-discharges in the anterior dorsal HPC; (3) primary unit after-discharges were induced by brief primary electrographic after-discharges; and (4) plasticity of primary electrographic after-discharges and inhibition of single neuron firing were induced by repetitive ATPDH. The results suggest that hippocampal pathophysiologic network along the temporal-septal axis of the HPC is re-established by the repetitive ATPDH. There are plastic interactions between single neurons and its network during this re-establishment, which may be involved in the generation of "seizure oscillation". Over-activation of an intrinsic inhibition of the HPC along its temporal-septal axis might be involved in hippocampal network epileptogenesis.

Electrical activities of bursting-firing neurons in epileptic network reestablishment of rat hippocampus / 生理学报

The purpose of our present work was to study the discharge of bursting-firing neurons (BFNs) in ipsilateral or contralateral hippocampus (HPC), and its relations to the reestablishment of local epileptic networks. The experiments were performed on 140 Sprague Dawley male rats (150-250 g). Acute tetanization (60 Hz, 2 s, 0.4 -0.6 mA) of the right posterior dorsal hippocampus (ATPDH) was administered to establish rat epilepsy model. The single unit discharges and the depth electrographs were simultaneously recorded from ipsilateral or contralateral HPC. In other experimental rats, acute tetanization of the right anterior dorsal HPC (ATADH) was used. Extracellular unit discharges in the CA1 region were simultaneously recorded from bilateral anterior dorsal hippocampi. Analysis of hippocampal BFN firing patterns before or after administration of the tetanization was focused on according to their location in the HPC epileptic networks in vivo. Single unit discharges of 138 hippocampal neurons were recorded from ipsilateral and/or contralateral anterior dorsal HPC. Of the 138 neurons recorded, 19 were BFNs. 13 BFNs were tetanus-evoked and the remaining 6 were spontaneous ones. The evoked reactions of the single hippocampal neuron induced by the tetanization mainly included: (1) the firing patterns of the BFNs in ipsilateral anterior dorsal HPC were obviously modulated by the ATPDH from tonic firing into rhythmic bursting. The bursting interspike intervals (BISI) decreased. (2) There were mild modulations of the firing patterns of the BFNs in contralateral anterior dorsal HPC following post-inhibition of the firing rate of single neuron induced by the ATPDH. The interspike intervals (ISI) increased obviously. (3) Post-facilitation of rhythmic bursting-firing of the BFNs in contralateral anterior dorsal HPC was induced by ATADH; both the ISI and the IBI increased. (4) Synchronous or asynchronous rhythmic bursting-firing of the BFNs and the network epileptiform events ipsilateral or contralateral anterior dorsal HPC were elicited by the ATPDH. The results obtained suggest that bursting-firing of single BFNs is produced by the ATPDH in the anterior dorsal HPC along the longitudinal axis of the ipsilateral HPC or across the hemisphere to the opposite HPC. Rhythmic activities of the BFN may be implicated in the epileptic network reestablishment of the HPC. On the other hand, synaptic modulation of the BFN temporal series might be responsible for pathophysiological information transmission in the HPC-epileptic network.