Identification of hepatosensitive region and their neural connections in the hippocampus of rats.

BACKGROUND: Visceral function localisation of the brain is very complex. For many years, people have been actively exploring the neural mechanism regulating visceral and substance metabolism, clarifying the complex relationship between the brain and peripheral nervous system related to the regulation of visceral activity, and analysing its complex neural pathways. The brain is the advanced centre of visceral function regulation. As an advanced centre for substance metabolism and visceral regulation, the hippocampus is crucial for regulating visceral function. The liver is the core organ of material metabolism, and its afferent signals are mainly projected to the nucleus of the solitary tract (NTS) through vagus nerve, and then they are projected to the hypothalamus and limbic system. MATERIALS AND METHODS: We placed a stereotaxic instrument on the head of each rat and performed craniotomy to open a window above the left hippocampus. We used gold-plated tungsten electrodes to monitor hippocampal neuronal discharges. Grounding was achieved using screws and silver wire. We electrically stimulated the liver branch of the vagus nerve and observed changes in hippocampal neuron discharges using a biological method; in this way, we identified hepatosensitive hippocampal region. We injected FluoroGold into this region and related brain areas. After 3 days, the rats were sacrificed and perfused; the hippocampi were fixed, dehydated, frozen, sectioned, and subjected to fluorescence microscopy. RESULTS: Nerve discharge frequency and amplitude significantly increased in the hippocampal CA3 region (AP: -4.9, ML: -5.1, DV: -5.0 mm). After FluoroGold was injected into the left hepatosensitive region in the hippocampus, labelled cells were found in the contralateral hippocampus, ipsilateral piriform cortex (PC), locus coeruleus (LC) and bilateral lateral hypothalamus (LHA); fluorescence in the ipsilateral hypothalamus was stronger than that of the contralateral hypothalamus. FluoroGold was injected into the LHA, PC, and LC; no labelled cells were found in the hippocampal CA3 region or in the control group. CONCLUSIONS: The hippocampal CA3 area of rats may contain a hepatosensitive region that plays important roles in the regulation of liver and other organ function. This region may receive input from the LHA, PC, and LC.

[Clinical effects of medical ozone autologous blood transfusion combined with Xingnaojing in the treatment of septic encephalopathy in burns].

Objective: To investigate the clinical effects of medical ozone autologous blood transfusion combined with Xingnaojing in the treatment of septic encephalopathy in burns. Methods: The retrospective cohort study was conducted. From August 2015 to May 2019, 90 patients with burn septic encephalopathy and conforming to the inclusion criteria were admitted to Zhengzhou First People's Hospital. Forty-six patients (25 males and 21 females, aged (35±4) years ) treated with Xingnaojing were included in Xingnaojing alone group, and forty-four patients (20 males and 24 females, aged (34±5) years) treated with medical ozone autologous blood transfusion combined with Xingnaojing were included in ozone autologous blood transfusion+Xingnaojing group. Heart rate, body temperature, mean arterial pressure, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score and Glasgow coma score (GCS) of patients in 2 groups were recorded before treatment and on 7 d after treatment. The blood-brain barrier injury markers including occludin, nitric oxide synthase (NOS), neuron-specific enolase (NSE), central nervous system specific protein S100ß, glial fibrillar acidic protein (GFAP), and excitatory amino acid (EAA) in serum of patients in 2 groups were detected before treatment and on 1, 3, and 7 d after treatment. Computer tomography perfusion imaging for brain was performed in patients of 2 groups to calculate the region of interest cerebral blood flow (rCBF), region of interest blood volume (rCBV), and region of interest mean transit time (rMTT) before treatment and on 1, 3, and 7 d after treatment. Data were statistically analyzed with chi-square test, analysis of variance for repeated measurement, independent sample t test, and Bonferroni correction. Results: On 7 d after treatment, heart rate, body temperature, and mean arterial pressure of patients in 2 groups were decreased compared with those before treatment, heart rate of patients in ozone autologous blood transfusion+Xingnaojing group was obviously higher than that in Xingnaojing alone group (t=2.886, P<0.01), body temperature of patients in ozone autologous blood transfusion+Xingnaojing group was obviously lower than that in Xingnaojing alone group (t=5.020, P<0.01), and mean arterial pressure of patients in 2 groups were close (t=0.472, P>0.05). On 7 d after treatment, APACHEⅡ score of patients in ozone autologous blood transfusion+Xingnaojing group was obviously lower than that in Xingnaojing alone group (t=3.797, P<0.01), and GCS of patients in ozone autologous blood transfusion+Xingnaojing group was obviously higher than that in Xingnaojing alone group (t=4.934, P<0.01). On 3 and 7 d after treatment, the levels of occludin, NOS, NSE, S100ß, GFAP, and EAA in serum of patients in ozone autologous blood transfusion+Xingnaojing group were significantly lower than those in Xingnaojing alone group (t=2.100, 2.090, 2.691, 2.013, 2.474, 2.635, 2.225, 4.011, 3.150, 2.691, 3.145, 2.781, P<0.05 or P<0.01). On 1, 3, and 7 d after treatment, rCBF and rCBV of patients in ozone autologous blood transfusion+Xingnaojing group were significantly increased compared with those in Xingnaojing alone group (t=3.127, 3.244, 3.883, 7.274, 3.661, 2.777, P<0.01). On 7 d after treatment, rMTT of patients in ozone autologous blood transfusion+Xingnaojing group was (3.02±0.57) s, which was significantly lower than (3.11±1.20) s in Xingnaojing alone group (t=2.409, P<0.05). Conclusions: Transfusion of medical ozone autologous blood combined with Xingnaojing therapy can effectively relieve brain injury and improve cerebral blood perfusion in patients with burn septic encephalopathy, which is with safety and credibility.

Deep insemination with sex-sorted Cashmere goat sperm processed in the presence of antioxidants.

Flow cytometrically sex-sorted sperm have been widely used for improving reproductive management in the dairy industry. However, the industrial application of this technology in other domestic species is largely limited by the lower fertility after insemination. The aim of this study was to investigate effects of antioxidant supplementation during the sex-sorting and freezing process on the quality and functions of sorted sperm from Liaoning Cashmere goats. We tested the effects of antioxidant supplementation during sex-sorting and freezing process, including ascorbic acid-2-glucoside AA-2G, glutathione, melatonin and vitamin C (VC), on the quality and functions of sex-sorted fresh and frozen-thawed sperm. Based on these experiments, we performed deep insemination with sex-sorted sperm using our improved strategy, in comparison to unsorted sperm. In Experiment 1, compared with control group and other antioxidants, AA-2G supplementation significantly alleviated the degradation of motility and viability of fresh sperm after sorting and showed the highest percentage of sperm with normal morphology. In addition, AA-2G supplementation showed an evident protection against the sorting process-induced membrane and acrosome damage. In Experiment 2, AA-2G supplementation was most effective in protecting motility, while melatonin supplementation appears to facilitate the degradation of quality of frozen-thawed sex-sorted sperm. In Experiment 3, we performed deep insemination with sperm that were sorted and frozen in the presence of AA-2G and obtained a satisfying pregnancy rate comparable to that from unsorted sperm. The results showed that AA-2G supplementation efficiently protects quality and function of both fresh and frozen-thawed sex-sorted sperm of Cashmere goats, thus obtaining a satisfying pregnancy outcome.

Phase IB study of sorafenib in combination with gemcitabine and cisplatin in patients with refractory solid tumors.

PURPOSE: Sorafenib (BAY 43-9006), a multikinase inhibitor, has been shown to inhibit tumor growth and tumor angiogenesis by targeting Raf kinase, vascular endothelial growth factor receptor, and platelet-derived growth factor receptor. This study investigated the safety, pharmacokinetics, and preliminary efficacy of sorafenib in combination with gemcitabine and cisplatin. METHODS: Patients with advanced solid tumors were treated with 75 mg/m(2) cisplatin on day 1 and 1,250 mg/m(2) gemcitabine on days 1 and 8 of each 21-day cycle. On day 5 of cycle 1, sorafenib 400 mg twice daily was started and continued throughout the complete treatment cycles without interruption. RESULTS: Nineteen patients were valid for safety analysis. The most frequent toxicities related to the cytotoxic agents were hematological disorders. Sorafenib-related toxicities were skin-related, gastrointestinal, and constitutional symptoms. No clinically relevant pharmacokinetic drug-drug interaction between sorafenib, cisplatin, and gemcitabine was detected. AUC(0-72) and C (max) of total and unbound platinum were only marginally changed by concomitant sorafenib. Concomitant sorafenib increased mean AUC and C (max) of gemcitabine by 12 and 21%. CONCLUSIONS: Sorafenib as continuous oral treatment in combination with gemcitabine and cisplatin demonstrated an acceptable safety profile. No clinically relevant pharmacokinetic interaction was detected. Preliminary antitumor activity, pharmacokinetic, and safety data support the recommendation of 400 mg sorafenib twice daily in combination with cisplatin and gemcitabine to be further evaluated in clinical studies.

Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis.

The effects of sorafenib--an oral multikinase inhibitor targeting the tumour and tumour vasculature--were evaluated in patients with advanced melanoma enrolled in a large multidisease Phase II randomised discontinuation trial (RDT). Enrolled patients received a 12-week run-in of sorafenib 400 mg twice daily (b.i.d.). Patients with changes in bi-dimensional tumour measurements <25% from baseline were then randomised to sorafenib or placebo for a further 12 weeks (ie to week 24). Patients with > or =25% tumour shrinkage after the run-in continued on open-label sorafenib, whereas those with > or =25% tumour growth discontinued treatment. This analysis focussed on secondary RDT end points: changes in bi-dimensional tumour measurements from baseline after 12 weeks and overall tumour responses (WHO criteria) at week 24, progression-free survival (PFS), safety and biomarkers (BRAF, KRAS and NRAS mutational status). Of 37 melanoma patients treated during the run-in phase, 34 were evaluable for response: one had > or =25% tumour shrinkage and remained on open-label sorafenib; six (16%) had <25% tumour growth and were randomised (placebo, n=3; sorafenib, n=3); and 27 had > or =25% tumour growth and discontinued. All three randomised sorafenib patients progressed by week 24; one remained on sorafenib for symptomatic relief. All three placebo patients progressed by week-24 and were re-started on sorafenib; one experienced disease re-stabilisation. Overall, the confirmed best responses for each of the 37 melanoma patients who received sorafenib were 19% stable disease (SD) (ie n=1 open-label; n=6 randomised), 62% (n=23) progressive disease (PD) and 19% (n=7) unevaluable. The overall median PFS was 11 weeks. The six randomised patients with SD had overall PFS values ranging from 16 to 34 weeks. The most common drug-related adverse events were dermatological (eg rash/desquamation, 51%; hand-foot skin reaction, 35%). There was no relationship between V600E BRAF status and disease stability. DNA was extracted from the biopsies of 17/22 patients. Six had V600E-positive tumours (n=4 had PD; n=1 had SD; n=1 unevaluable for response), and 11 had tumours containing wild-type BRAF (n=9 PD; n=1 SD; n=1 unevaluable for response). In conclusion, sorafenib is well tolerated but has little or no antitumour activity in advanced melanoma patients as a single agent at the dose evaluated (400 mg b.i.d.). Ongoing trials in advanced melanoma are evaluating sorafenib combination therapies.

First total synthesis of martinellic acid, a naturally occurring bradykinin receptor antagonist.

[reaction: see text] The first total synthesis of martinellic acid, a naturally occurring bradykinin receptor antagonist, via a CuI-catalyzed coupling reaction of beta-amino ester 6 with 1,4-diiodobenzene and a guanylation reaction of secondary amine 3 under mild conditions as key steps, is described.

[A preliminary study of two Chinese herbs protective tablets on some Chinese traditional medicines].

The protective action of 2 tablets of Chinese herb to 5 Chinese traditional medicines against harm of insects and mildews was tested. It was found that 2 tablets have a obvious effects of insect-repellency and mouthproof in the test with Homalomena occulta and Prunus armeniaca, the bore in the medicinal materials was decreased 94.95% and 95.55% respectively than that of check. The tablets have some effects of mildewproof in the test with Tussilago farfara.

[Preliminary studies on chemical constituents and pharmacological action of Eclipta prostrata L].

OBJECTIVE: To study the pharmacologically active components of Eclipta prostrata. METHOD: The components were extracted by alcohol and isolated by silica gel column and subjected to pharmacological screening. RESULT: Four compounds were isolated from E. prostrata, of which two were identified as stigmasterol and alpha-terthienyl. CONCLUSION: alpha-Terthienyl was isolated from the plant for the first time. The EtOAc part of alcoholic extraction exhibits significant hepatoprotective activity against carbon terachloride-induced liver injury in rats.

[Effects of Sichuan herba Epimedii on the concentration of plasma middle molecular substances and sulfhydryl group of "yang-deficiency" model animal].

The effects of tonifying the kidney and strengthening the "Yang" produced by the extracts of Chinese herbs Epimedium wushanense and E. pubescens were studied in this paper. The results showed that both two herbs could decrease the concentration of plasma middle molecular substances and increase the concentration of plasma sulfhydryl group of "Yang-deficiency" model mice, thus suggesting that the above-said tonifying and strengthening effects of Herba Epimedii may result from its effects on middle molecular substances and sulfhydryl group, so as to strengthen the body resistance and eliminate the invading pathogenic factors.

[Influence of acupuncture on blood pressure, contents of NE, DA and 5-HT of SHR and the interrelation between blood pressure and whole blood viscosity].

Twenty spontaneous hypertensive rats (SHR) with systolic blood pressure (SBP) >or= 20 kPa were chosen and divided randomly into two groups (acupuncture group and control group). The former was acupunctured on bilateral Quchi (L1 11), Zusanli (ST 36). Another 46 immature SHRs which were about 7-week-old with SBP ranged from 16 kPa to 20 kPa were given 10% high molecular weight dextran (HMWD) or normal saline by intervention respectively. The results showed: 1. After three course of acupuncture, SHRs' SBP dropped remarkably from 25.493 +/- 0.73 kPa to 19.547 +/- 0.555 kPa (P < 0.01); 2. After three courses of acupuncture, NE and 5-HT contents in plasma were lowered (P < 0.05, < 0.01) and DA content in plasma was increased (P < 0.05) compared with that in the control group. 3. After three course of acupuncture, NE content in brainstem, hypothalamus, cerebral cortex increased (P < 0.005-0.01) and DA content in brainstem, cerebral cortex increased remarkably (P < 0.005-0.01) compared with that in the control group. 5-HT content in brainstem, hypothalamus, and cerebral cortex increased obviously compared with that in the control group. 4. After 1 or 2 hours of intervention of 10% HMWD to immature SHR, the whole blood viscosity and blood pressure rise remarkably compared with normal saline group. The experiment implies that the mechanism of lowering the blood pressure of SHR by acupuncture lies in that it can adjust NE, DA and 5-HT contents in plasma and central nervous system to adjust the activity of sympathetic, reduce whole blood viscosity etc.

cDNA cloning of a cytosolic protein tyrosine phosphatase (RKPTP) from rat kidney.

A rat cDNA encoding a non-receptor type phosphotyrosine phosphatase (PTPase; EC 3.1.3.48) was identified. The 1608 bp cDNA contains a single open reading frame that predicts a 382 amino acid protein with M(r) 44,438. The predicted protein has no apparent signal or transmembrane sequences, suggesting that it is a cytosolic protein. The C-terminal region has a PTPase catalytic domain that has 40-50% nucleic acid homology to other known PTPases. The N-terminal region has little amino acid sequence homology to any other known sequences. The recombinant protein of the cloned cDNA expressed in Escherichia coli was shown to possess PTPase activity using myelin basic protein, tyrosine phosphorylated by p43v-abl tyrosine kinase, as a substrate.

[Studies on the effect of immunoenhancing reagent "425" on egg granuloma formation in mice infected with Schistosoma japonicum].

Fourteen--34 days after Schistosoma japonicum-infected mice were injected intraperitoneally with immunoenhancing reagent, Chinese angelica root extract ("425"), the specific antibody (IgG) levels were significantly higher in Group III (362.67 +/- 162.21 - 480.00 +/- 289.45) than the control group (66.67 +/- 39.68 - 245.33 +/- 101.56) in experiment one, and in Group II (488.00 +/- 320.38 - 768.00 +/- 267.38) than the control group (256.00 +/- 189.07 - 394.67 +/- 141.06) in experiment two. The egg granulomatous formation were markedly diminished in the injected mice. The ratios of granulomas vs. eggs' mean diameters of Group III of mice were 5.24 +/- 1.04 - 3.95 +/- 0.77 and those of the control group were 6.59 +/- 1.19 - 5.29 +/- 0.94 in experiment one, those of the group II were 3.75 +/- 0.71 - 4.15 +/- 0.73 and those of the control group were 4.94 +/- 0.81 - 5.36 +/- 0.97 in experiment two. Meantime the egg antigen levels in the injected mice might be lower. This study shows that the control of immunomodulation of granulomatous formation in the hosts injected with immunoenhance reagent "425" can be induced.