Effect of Shionone on Neuron Apoptosis After Spinal Cord Injury in Mice / 中国医学科学院学报

Objective To explore the effect of shionone(SHI)on motor function in the mouse model of spinal cord injury(SCI)and probe into the underlying molecular mechanism.Methods C57BL/6 mice were treated to induce the SCI model and then assigned into a model group(SCI group),a SCI+SHI group,and a sham surgery(control)group.The Basso mouse scale(BMS)score was determined to evaluate the recovery of motor function in SCI mice.Hematoxylin-eosin(HE)staining,Nissl staining,and immunofluorescence staining were employed to examine the fibrosis,morphological changes of neurons,and neuron apoptosis in the spinal cord tissue of SCI mice,respectively.The mouse hippocampal neuronal cell line HT22 was cultured in vitro and then classified into tumor necrosis factor α(TNF-α)induction and SHI groups.Western blotting was employed to determine the expression of apoptosis-associated proteins.Network pharmacology,gene ontology annotation,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were employed to predict the possible molecular targets and signaling pathways of SHI in promoting functional recovery from SCI.Furthermore,the prediction results were verified by in vitro and in vivo experiments.Results Compared with the SCI group,the SCI+SHI group showed increased BMS score on days 21,28,35,and 42(P=0.003,P=0.004,P=0.023,and P=0.007,respectively),reduced area of spinal cord fibrosis(P=0.021),increased neurons survived(P=0.001),and down-regulated expression of cleaved cysteine aspastic acid-specific protease 3(cleaved Caspase-3)(P=0.017).Compared with the TNF-α group,the SHI group presented down-regulated expression levels of cleaved Caspase-3 and Bax(P=0.010,P=0.001)and up-regulated expression level of Bcl-2(P=0.001).The results of bioinformatics analysis showed that SHI might improve the motor function of SCI mice via the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.The results of in vivo and in vitro experiments showed that SHI inhibited the phosphorylation of PI3K and Akt in SCI mice or HT22 cells exposed to TNF-α(all P<0.05).The number of apoptotic HT22 cells after treatment with insulin-like growth factor 1 was higher than that in the SHI group(P=0.003).Conclusion SHI may inhibit neuron apoptosis via the PI3K/Akt signaling pathway,thereby promoting the recovery of motor function in SCI mice.

Prostate-derived IL-1β upregulates expression of NMDA receptor in the paraventricular nucleus and shortens ejaculation latency in rats with experimental autoimmune prostatitis / 亚洲男科学杂志(英文版)

Experimental autoimmune prostatitis (EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid (NMDA) receptors in the paraventricular nucleus (PVN). However, the mechanism has not yet been elucidated. Herein, we screened out the target prostate-derived inflammation cytokines (PDICs) by comparing the inflammatory cytokine levels in peripheral blood and cerebrospinal fluid (CSF) between EAP rats and their controls. After identifying the target PDIC, qualified males in initial copulatory behavior testing (CBT) were subjected to implanting tubes onto bilateral PVN. Next, they were randomly divided into four subgroups (EAP-1, EAP-2, Control-1, and Control-2). After 1-week recovery, EAP-1 rats were microinjected with the target PDIC inhibitor, Control-1 rats were microinjected with the target PDIC, while the EAP-2 and Control-2 subgroups were only treated with the same amount of artificial CSF (aCSF). Results showed that only interleukin-1β(IL-1β) had significantly increased mRNA-expression in the prostate of EAP rats compared to the controls (P < 0.001) and significantly higher protein concentrations in both the serum (P = 0.001) and CSF (P < 0.001) of the EAP groups compared to the Control groups. Therefore, IL-1β was identified as the target PDIC which crosses the blood-brain barrier, thereby influencing the central nervous system. Moreover, the EAP-1 subgroup displayed a gradually prolonged ejaculation latency (EL) in the last three CBTs (all P < 0.01) and a significantly lower expression of NMDA NR1 subunit in the PVN (P = 0.043) compared to the respective control groups after a 10-day central administration of IL-1β inhibitors. However, the Control-1 subgroup showed a gradually shortened EL (P < 0.01) and a significantly higher NR1 expression (P = 0.004) after homochronous IL-1β administration. Therefore, we identified IL-1β as the primary PDIC which shortens EL in EAP rats. However, further studies should be conducted to elucidate the specific molecular mechanisms through which IL-1β upregulates NMDA expression.

Two Serum Free Light Chain Detection Systems in the Diagnosis of Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the comparability of the Freelite, Binding Site, Beckman and N Latex FLC, Siemens in the detection of serum free light chain (sFLC) .@*METHODS@#Fifty newly diagnosed multiple myeloma (MM) patients in Tianjin Institute of Blood Research from November 2019 to February 2020 were enrolled. The two systems (Freelite, Binding Site, Beckman and N Latex FLC, Siemens) were used to detect the sFLC of the samples. Outlier detection was performed by ESD method, methodological comparison and deviation assessment were performed by Passing-Bablok regression and Bland-Altman regression.@*RESULTS@#Both the systems could quantitatively analyze free kappa light chain serum samples and free lambda light chain samples. Freelite, Binding Site, Beckman and N Latex FLC, Siemens free light chain test showed FLC-κ：36.5 (6.5, 194), 40.5 (6.94, 288), FLC-λ: 30.1 (4.3, 170.5), 35.1 (2.28, 526), rFLC (FLC-κ/ FLC-λ) : 0.82 (0.05, 43.25), 1.03 (0.03, 32.04), dFLC (｜FLC-κ- FLC-λ｜) : -5.8 (-161.97, 183.7), 1.1 (-505.1, 279.01), which existed no outliers. There were systematic differences, and the deviation level was not within the clinically acceptable range.@*CONCLUSION@#Both the systems can meet the needs of clinical diagnosis and treatment, but there is a significant deviation between the two systems, the results are not comparable, and should be analyzed separately. In particular, the same system should be selected for monitoring the prognosis of MM.

Angiotensin Type 1 Receptors and Superoxide Anion Production in Hypothalamic Paraventricular Nucleus Contribute to Capsaicin-Induced Excitatory Renal Reflex and Sympathetic Activation / 神经科学通报·英文版

Chemical stimulation of the kidney increases sympathetic activity and blood pressure in rats. The hypothalamic paraventricular nucleus (PVN) is important in mediating the excitatory renal reflex (ERR). In this study, we examined the role of molecular signaling in the PVN in mediating the capsaicin-induced ERR and sympathetic activation. Bilateral PVN microinjections were performed in rats under anesthesia. The ERR was elicited by infusion of capsaicin into the cortico-medullary border of the right kidney. The reflex was evaluated as the capsaicin-induced changes in left renal sympathetic nerve activity and mean arterial pressure. Blockade of angiotensin type 1 receptors with losartan or inhibition of angiotensin-converting enzyme with captopril in the PVN abolished the capsaicin-induced ERR. Renal infusion of capsaicin significantly increased NAD(P)H oxidase activity and superoxide anion production in the PVN, which were prevented by ipsilateral renal denervation or microinjection of losartan into the PVN. Furthermore, either scavenging of superoxide anions or inhibition of NAD(P)H oxidase in the PVN abolished the capsaicin-induced ERR. We conclude that the ERR induced by renal infusion of capsaicin is mediated by angiotensin type 1 receptor-related NAD(P)H oxidase activation and superoxide anion production within the PVN.

Intermedin in Paraventricular Nucleus Attenuates Sympathoexcitation and Decreases TLR4-Mediated Sympathetic Activation via Adrenomedullin Receptors in Rats with Obesity-Related Hypertension / 神经科学通报·英文版

Intermedin/adrenomedullin-2 (IMD/AM2), a member of the calcitonin gene-related peptide/AM family, plays an important role in protecting the cardiovascular system. However, its role in the enhanced sympathoexcitation in obesity-related hypertension is unknown. In this study, we investigated the effects of IMD in the paraventricular nucleus (PVN) of the hypothalamus on sympathetic nerve activity (SNA), and lipopolysaccharide (LPS)-induced sympathetic activation in obesity-related hypertensive (OH) rats induced by a high-fat diet for 12 weeks. Acute experiments were performed under anesthesia. The dynamic alterations of sympathetic outflow were evaluated as changes in renal SNA and mean arterial pressure (MAP) in response to specific drugs. Male rats were fed a control diet (12% kcal as fat) or a high-fat diet (42% kcal as fat) for 12 weeks to induce OH. The results showed that IMD protein in the PVN was downregulated, but Toll-like receptor 4 (TLR4) and plasma norepinephrine (NE, indicating sympathetic hyperactivity) levels, and systolic blood pressure were increased in OH rats. LPS (0.5 µg/50 nL)-induced enhancement of renal SNA and MAP was greater in OH rats than in obese or control rats. Bilateral PVN microinjection of IMD (50 pmol) caused greater decreases in renal SNA and MAP in OH rats than in control rats, and inhibited LPS-induced sympathetic activation, and these were effectively prevented in OH rats by pretreatment with the AM receptor antagonist AM22-52. The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) inhibitor U0126 in the PVN partially reversed the LPS-induced enhancement of SNA. However, IMD in the PVN decreased the LPS-induced ERK activation, which was also effectively prevented by AM22-52. Chronic IMD administration resulted in significant reductions in the plasma NE level and blood pressure in OH rats. Moreover, IMD lowered the TLR4 protein expression and ERK activation in the PVN, and decreased the LPS-induced sympathetic overactivity. These results indicate that IMD in the PVN attenuates SNA and hypertension, and decreases the ERK activation implicated in the LPS-induced enhancement of SNA in OH rats, and this is mediated by AM receptors.

Blockade of Endogenous Angiotensin-(1-7) in Hypothalamic Paraventricular Nucleus Attenuates High Salt-Induced Sympathoexcitation and Hypertension / 神经科学通报·英文版

Angiotensin (Ang)-(1-7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1-7) in the hypothalamic paraventricular nucleus (PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines (PICs) and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt (8% NaCl) or a normal salt diet (0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1-7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma norepinephrine (NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 expression and superoxide production in the PVN. Microinjection of A-779 (3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1-7) in the PVN, through modulation of PICs and oxidative stress.

Chronic Intracerebroventricular Infusion of Metformin Inhibits Salt-Sensitive Hypertension via Attenuation of Oxidative Stress and Neurohormonal Excitation in Rat Paraventricular Nucleus / 神经科学通报·英文版

Metformin (MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension. This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rats by inhibiting oxidative stress in the hypothalamic paraventricular nucleus (PVN). Salt-sensitive rats received a high-salt (HS) diet to induce hypertension, or a normal-salt (NS) diet as control. At the same time, they received intracerebroventricular (ICV) infusion of MET or vehicle for 6 weeks. We found that HS rats had higher oxidative stress levels and mean arterial pressure (MAP) than NS rats. ICV infusion of MET attenuated MAP and reduced plasma norepinephrine levels in HS rats. It also decreased reactive oxygen species and the expression of subunits of NAD(P)H oxidase, improved the superoxide dismutase activity, reduced components of the renin-angiotensin system, and altered neurotransmitters in the PVN. Our findings suggest that central MET administration lowers MAP in salt-sensitive hypertension via attenuating oxidative stress, inhibiting the renin-angiotensin system, and restoring the balance between excitatory and inhibitory neurotransmitters in the PVN.

Clinical features and laboratory data analysis of Aeromonas bacteremia with hematological diseases / 中华血液学杂志

Objective: To investigate the clinical and laboratory features of Aeromonas bacteremia in patients with hematological diseases, and provide evidence for the prevention and treatment of Aeromonas infection. Methods: A retrospective study of patients with bloodstream infection of Aeromonas in our hospital from January 2014 to December 2018 was carried out. The clinical characteristics, antimicrobial susceptibility, infection seasons, antimicrobial therapy and evolution were analyzed. Results: A total of 42 patients with hematological diseases had Aeromonas bloodstream infection within 5 years. Among them, 39 cases (92.9%) of bloodstream infection occurred in the stage of neutropenia. The median time of fever was 4 (1-27) d, 22 (52.4%) patients only had fever, 6 (14.3%) with gastrointestinal symptoms (abdominal pain, diarrhea, nausea, upper gastrointestinal bleeding) , 8 (19.0%) with pulmonary infection, 13 (31.0%) with skin and soft tissue infections. Seven patients (16.7%) died with skin and soft tissue infection. The resistance of Aeromonas to carbapenems was 68.3%-70.7%, while the resistance rate to cephalosporins, quinolones and aminoglycosides were less than 10%. Conclusions: Aeromonas bacteremia in patients with hematological diseases mainly occur in the neutropenia stage, usually with symptom like fever. The mortality is increased when accompanied by skin and soft tissue infection. Antibiotic use should be based on susceptibility results, and avoid the use of carbapenems.

Differences in sympathetic nervous system activity and NMDA receptor levels within the hypothalamic paraventricular nucleus in rats with differential ejaculatory behavior / 亚洲男科学杂志(英文版)

Differences in intravaginal ejaculation latency reflect normal biological variation, but the causes are poorly understood. Here, we investigated whether variation in ejaculation latency in an experimental rat model is related to altered sympathetic nervous system (SNS) activity and expression of N-methyl-D-aspartic acid (NMDA) receptors in the paraventricular nucleus of the hypothalamus (PVN). Male rats were classified as "sluggish," "normal," and "rapid" ejaculators on the basis of ejaculation frequency during copulatory behavioral testing. The lumbar splanchnic nerve activity baselines in these groups were not significantly different at 1460 ± 480 mV, 1660 ± 600 mV, and 1680 ± 490 mV, respectively (P = 0.71). However, SNS sensitivity was remarkably different between the groups (P < 0.01), being 28.9% ± 8.1% in "sluggish," 48.4% ± 7.5% in "normal," and 88.7% ± 7.4% in "rapid" groups. Compared with "normal" ejaculators, the percentage of neurons expressing NMDA receptors in the PVN of "rapid" ejaculators was significantly higher, whereas it was significantly lower in "sluggish" ejaculators (P = 0.01). In addition, there was a positive correlation between the expression of NMDA receptors in the PVN and SNS sensitivity (r = 0.876, P = 0.02). This study shows that intravaginal ejaculatory latency is associated with SNS activity and is mediated by NMDA receptors in the PVN.

Clinical effect of superselective arterial embolization for the treatment of massive haemorrhage from pelvic fracture / 中国骨伤

<p><b>OBJECTIVE</b>To investigate feasibility and curative effect of superselective arterial embolization for the treatment of massive haemorrhage from pelvic fracture.</p><p><b>METHODS</b>From March 2008 to February 2016, clinical data of 65 patients with massive haemorrhage from pelvic fracture were collected and analyzed, and patients were divided into non-embolic and embolic group according to whether perform vascular thrombosis. Thirty-three patients were in non-embolic group including 26 males and 7 females aged from 21 to 64 years old with an average of(39.2±5.7) years old, the time from injury to operation ranged from 1.1 to 4.8 h with an average of (2.2±0.4) h; 12 cases were type B and 21 cases were type C according to AO/Tile classification; injury severity score (ISS) ranged from 25 to 42 with an average of (37.7±7.5); shock index score ranged from 1.7 to 2.4 with an average of 2.1±0.3; treated with blood transfusion and fluid infusion. Thirty-two patients in embolic group, including 25 males and 7 females aged from 22 to 65 years old with an average of(38.1±4.5) years old; the time from injury to operation ranged from 1.2 to 4.8 h with an average of (2.1± 0.5) h; 14 cases were type B and 18 cases were type C according to AO/Tile classification; ISS ranged from 26 to 43 with an average of 38.9±4.5; shock index score ranged from 1.6 to 2.4 with an average of 2.2±0.2; treated by blood transfusion and fluid infusion with superselective arterial embolization. Blood transfusion volume, fluid infusion volume, shock correction time and survival rate were observed and compared, effective rate of hemostasis and postoperative complications were compared.</p><p><b>RESULTS</b>Thirty-seven artery were injured in embolic group, hemostasis were controlled at 3 h after operation, and hemodynamics turned to stable. There were significant difference in blood transfusion volume, fluid infusion volume, shock correction time between non-embolic and embolic group, and embolic group performed better. Survival rate in embolic group was also better than that of non-embolic group, and had significant difference. While there was obvious differences in complications(χ²=4.03,=0.045).</p><p><b>CONCLUSIONS</b>Superselective arterial embolization for massive haemorrhage from pelvic fracture could effective hemostasis, reduce blood transfusion and fluid infusion volume and occurrence rate of shock, moreover improve survival rate and deserves promotion.</p>

Analysis of risk factors for spontaneous rupture of hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the risk factors for spontaneous rupture of hepatocellular carcinoma (SRHC).</p><p><b>METHODS</b>A retrospective analysis of 34 consecutive patients with SRHC treated by emergency interventional embolization in our hospital from July 2003 to July 2011 was conducted. General condition, laboratory examination and imaging data were analyzed, and compared with the data of 34 patients with primary hepatocellular carcinoma but without rupture, randomly selected from 215 concurrent patients. The patients with SRHC were selected for risk factor analysis, and the non-SRHC patients were taken as control group.</p><p><b>RESULTS</b>No significant difference between the SRHC group and control group was found in age, sex, Child-Turcotte-Pugh (CTP) grade, Barcelona clinic liver cancer (BCLC) stage, HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, prothrombin time (PT), thrombin time (TT), international normalized ratio (INR), glucose (GLU), cirrhosis, portal tumor thrombus, the maximum diameter of tumor, location, and cholecystitis or cholelithiasis. The univariate analysis showed that activated partial thromboplastin time (APTT), lower or normal plasma fibrinogen (FIB) level, alpha fetoprotein (AFP), tumor protrusion > 1 cm above the liver surface were all associated with increased risk of SRHC (P < 0.05). Multivariate analysis only showed that lower or normal level of FIB (P = 0.033) and tumor protrusion > 1 cm above the liver surface (P = 0.041) were significant independent risk factors for SRHC.</p><p><b>CONCLUSION</b>Lower or normal level of FIB and tumor protrusion > 1 cm above the liver surface are significant independent risk factors for spontaneous rupture of hepatocellular carcinoma.</p>

Case-control study on transcatheter artery embolization for massive bleeding due to pelvic fractures / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the techniques and curative effects of transcatheter artery embolization (TAE) for massive bleeding due to pelvic fractures.</p><p><b>METHODS</b>The clinical data of 92 patients with haemorrhage due to pelvic fractures from March 1998 to February 2008 were retrospectively analyzed. Among 53 patients treated conservatively such as massive transfusion and fluid infusion in the control group, 43 patients were male and 10 patients were female, ranging in age from 27 to 61 years, averaged (37.2 +/- 5.7) years. Among 39 patients who were hemodynamically unstable or had evidences of ongoing hemorrhage required TAE, 26 patients were male and 13 patients were female, ranging in age from 26 to 62 years, with a mean age of (35.3 +/- 9.5) years. The clinical date such as blood or fluid transfusion volume, shock redress time and survival rate were compared between the two groups. The hemostatic efficiency and complications of the surgery were also analyzed.</p><p><b>RESULTS</b>The average hemostasis time of TAE group was 2 hours. There were no intraoperative injuries of blood vessels, nerve or vital organs. Three patients had lower limbs numbness and 5 patients had gluteal skin redness after the operation. The blood transfusion or fluid infusion volume, shock redress time and survival rate were all significantly better than those in the conservative group.</p><p><b>CONCLUSIONS</b>TAE is an early,rapid and effective method in controlling haemorrhage due to pelvic fractures.</p>

Study on eco-climatic applicability of Angelica sinensis / 中国中药杂志

<p><b>OBJECTIVE</b>In the interest of establish planting base of Angelica sinensis on a large scale, enhance economic benefit, and improve decision-making reasons, the eco-climatic applicability of A. sinensis was studied.</p><p><b>METHOD</b>Using integral regression, eco-climatic applicability and the effect of meteorological conditions for the yield of A. sinensis' were analysed by field experimental data.</p><p><b>RESULT</b>Selected > or =0 degrees C accumulated temperature and annual precipitation as leading index, altitude as assistant index, yield and rate of finished products as reference index, the integrated eco-climatic division index and the planting division applicability of A. sinensis was confirmed.</p><p><b>CONCLUSION</b>Accordancing to theory of climate similitude and leading index summarisation, combining with assistant index and reference index, the integrated division index of eco-climate was confirmed. The planting division of co-climate applicability was divided into 5 grades as best suitable, suitable hypo-suitable, just suitable and no suitable regions. At the same time,the way to enhanced utilizing efficiency of eco-climate resources was brought forward.</p>

Reduced nitric oxide in the rostral ventrolateral medulla enhances cardiac sympathetic afferent reflex in rats with chronic heart failure / 生理学报

The purpose of this study was to determine the effect of nitric oxide (NO) in the rostral ventrolateral medulla (RVLM) on the central integration of the cardiac sympathetic afferent reflex (CSAR) in normal rats and in rats with coronary ligation-induced chronic heart failure (CHF). Under alpha-chloralose and urethane anesthesia, mean arterial pressure, heart rate and renal sympathetic nerve activity (RSNA) were recorded at baseline and during elicitation of the CSAR evoked by electrical stimulation of the cardiac afferent sympathetic nerves in sino-aortic denervated and cervical vagotomized rats. A cannula was inserted into the left RVLM for microinjection of NO synthase inhibitor, S-methyl-L-thiocitruline (MeTC) or NO donor, S-nitroso-N-acetyl-penicillamine (SNAP). The CSAR was tested by electrical stimulation (5, 10, 20 and 30 Hz at 10 V for 1 ms) of the afferent cardiac sympathetic nerves. It was observed that (1) the responses of RSNA to stimulation were enhanced in rats with CHF; (2) MeTC (80 nmol) potentiated the responses of RSNA to stimulation in sham rats but not in rats with CHF; (3) SNAP (50 nmol) depressed the enhanced RSNA response to stimulation in CHF rats but had no effect in sham rats; and (4) MeTC increased the baseline RSNA and MAP only in sham rats, but SNAP inhibited the baseline RSNA and MAP in both sham and CHF rats. These results indicate that reductance of NO in the RVLM is involved in the augmentation of CSAR in CHF rats.

Baroreceptor reflex in heart failure / 生理学报

Congestive heart failure is a syndrome that is usually initiated by a reduction in pump function of the heart, i.e. a decrease in cardiac output. Initially, a reduction in cardiac output leads to unloading of baroreceptor reflex that, in turn, increases heart rate through vago-sympathetic mechanisms and total peripheral resistance via an increase in sympathetic outflow to vascular beds. In this review we are thinking on how baroreceptor reflex plays a role in the abnormal control of the circulation in heart failure. This review and our recent studies suggest that: (1) baroreceptor reflex is blunted in heart failure; (2) central angiotensin II and reactive oxygen species play an important role in blunted baroreceptor reflex; (3) cardiac sympathetic afferent stimulation and chemoreceptor reflex inhibit baroreceptor reflex; and (4) exercise training normalizes abnormal reflexes in the heart failure state.