[Retrospective study on the efficacy and safety of low dose apatinib in reversing chemotherapy resistance in sarcoma].

Objective: To explore whether apatinib can reverse the chemotherapy resistance of patients with advanced sarcoma. Methods: The clinical data of advanced sarcoma patients after chemotherapy who received the original chemotherapy regimen combined with low-dose apatinib in Cancer Center of Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from May 2018 to November 2021 were collected retrospectively to evaluate the efficacy and safety of this regimen. The primary end point was progression-free survival (PFS), and the secondary end points were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and adverse events (AE). The patients were grouped according to the diagnosis: osteosarcoma, soft tissue sarcoma and undifferentiated small round cell sarcoma. And the benefits of combination treatment was investigated with the stratified analysis of best outcome of combined therapy, lines of chemotherapy received, best response and PFS of original chemotherapy. Results: A total of 30 patients were included in this study, including 20 males and 10 females. The mean age was (25.6±14.7) years. There were 9 cases of osteosarcoma, 11 cases of soft tissue sarcoma and 10 cases of undifferentiated small round cell sarcoma. No patient achieved complete response, 8 patients (26.7%) achieved partial response, 19 patients (63.3%) achieved disease stability, the ORR was 26.7%(8/30), and the DCR was 90.0%(27/30). The median PFS and OS were 4.1 and 13.1 months respectively. Among the three different subtypes of sarcoma, the ORR of osteosarcoma was 44.4% (4/9), the median PFS was 4.1 months, and the median OS was not yet achieved; the ORR of undifferentiated small round cell sarcoma was 40% (4/10), the median PFS was 6.4 months, and the median OS was 10.9 months; No response was observed in soft tissue sarcoma, and the median PFS and median OS was 3.5 and 7.3 months respectively. Patients who achieved objective response had better PFS than patients with stable disease (12.8 vs 3.8 months, P=0.015), and patients with PFS≥ 6 months of original chemotherapy had better PFS benefits (12.7 vs 2.7 months, P<0.001). However, the number of original chemotherapy lines and the best response of original chemotherapy had no significant effect on the PFS of this combination regimen. In terms of safety, the related toxicity of apatinib was no more than grade 2, and the grade 4 chemotherapy-related adverse reactions was mainly hematological toxicity, of which 2 patients interrupted treatment because of febrile neutropenia. Conclusion: Low dose apatinib is effective in reversing chemotherapy resistance of osteosarcoma and undifferentiated small round cell sarcoma with acceptable adverse reactions.

[Technology specification of bedside hypertonic saline-contrast electrical impedance tomography of lung perfusion and clinical application].

Bedside hypertonic saline-contrast electrical impedance tomography (EIT) method for lung perfusion evaluation has several advantages of bedside, simple, noninvasive and radiation-free. For a long time, EIT perfusion image of hypertonic saline was mostly limited to animal experiments, and related clinical research is in the ascendant. This technical specification for clinical application is reached based on our previous researches, review of literatures in this field. The purpose of this technical specification is to facilitate the unified and standardized use of hypertonic saline-contrast EIT technology for regional lung perfusion, to evaluate the safety and quality control of the technology, and to unify the results.

[Clinical characteristics of hepatic flare and efficacy of antiviral therapy in pregnant women with chronic hepatitis B virus infection].

Objective: To analyze the clinical characteristics of hepatic flare and evaluate efficacy of antiviral treatment in pregnant women with chronic HBV infection. Methods: A single-center, open-label, prospective study was conducted, and pregnant women with chronic HBV infection were enrolled. Liver function, HBV serum markers and HBV DNA of pregnant women with chronic HBV infection were reviewed during every 4 to 12 weeks of gestation period. The proportion and clinical characteristics of hepatitis flare during pregnancy were observed. Logistic regression analysis was used to predict hepatic flare in pregnant women with chronic HBV infection. Antiviral therapy with telbivudine (LdT) or tenofovir dipivoxil (TDF) was used to treat hepatic flare during pregnancy. Sequential entecavir (ETV) or TDF was applied after the delivery. Treatment course and drug withdrawal in pregnant women with hepatic flare was the same as those of the general patients with chronic hepatitis B. Liver function, HBV serum markers and HBV DNA were measured in pregnant women with hepatic flare at different time points (4, 12, 24 and 52 weeks). A t-test was used to compare the hepatic flare in pregnant women with and without hepatitis group. HBsAg and HBeAg were used to quantify the receiver operating characteristic (ROC) curve of pregnant women with hepatic flare during pregnancy. Area under the ROC curve was used to calculate the optimal cut-off value corresponding to the maximum sensitivity and specificity of the ROC curve. Results: Of the 220 pregnant women with chronic HBV infection, 55 (25%) had hepatitis flare during pregnancy and received antiviral treatment. Among the 55 women with hepatic flare during gestation, 47 (85.46%) had hepatic flare in the mid-second trimester (12-24 weeks); average peak value of alanine aminotransferase (ALT) was 220.62 U/L, and the average peak value of ALT in 32 cases (58.18%) of pregnant women with hepatic flare was between 2-5 × ULN. HBsAg and HBeAg quantification were significantly lower in pregnant women with hepatic flare during pregnancy than with non-hepatitis (t = -3.745, P < 0.001; t = -2.186, P = 0.030). Multivariate logistic regression analysis showed that pregnant women with HBeAg < 3.065 log10 s/co were 7.576 times more likely to have hepatic flare during pregnancy (95% confidence interval: 3.779-15.190). ALT normalization, undetectable HBV DNA levels, HBeAg loss and HBeAg seroconversion in 55 pregnant women with hepatic flare at 52-week treatment was 100% (55/55), 74.55% (41/55), 47.27% (26/55) and 41.82% (23/55), respectively. HBsAg quantification at 52 weeks was significantly lower than baseline HBsAg quantification (3.32 + 0.37) log(10) IU/ml and (3.95 + 0.40) log(10) IU/ml; t = 8.465, P < 0.001). Conclusion: Hepatic flare often occurs in the second trimester of pregnancy in pregnant women with chronic HBV infection and baseline HBeAg quantification is an independent predictor of hepatic flare. HBeAg seroconversion rate increased at 52 weeks after antiviral therapy.

[An analysis of coping styles and subjective well-being among nurses in the emergency treatment room of grade A tertiary hospitals in a province of China].

Objective: To investigate the coping styles and subjective well-being of nurses in the emergency treatment room of grade A tertiary hospitals in a province of China, and to explore the relationship between coping styles and subjective well-being. Methods: In January 2016, 189 nurses in the emergency treatment room were selected from 9 grade A tertiary hospitals in a province of China by random sampling. The general data, coping styles, and subjective well-being of these nurses were analyzed using the general questionnaire, coping style questionnaire, and Campbell index of well-being scale, respectively. Results: The total score of subjective well-being of nurses in the emergency treatment room was 7.54, and the subjective well-being was significantly different between the nurses with different professional titles and between those with different education levels (F=3.46 and 3.47, both P<0.05). The score of illusion coping style differed significantly across the nurses of different ages (F=5.17, P<0.05) , the scores of self-reproach, illusion, and withdrawal coping styles differed significantly across the nurses with different nursing years (F=3.99, 5.30, and 4.97, all P<0.05) , and the score of illusion coping style differed significantly across the nurses with different education levels (F=5.09, P<0.05). Most (71.9%) of the nurses in the emergency treatment room adopted the mature coping style. Subjective well-being was positively correlated with problem-solving, help-seeking, and rationalization (r=0.232, 0.018, and 0.167, all P<0.05) and negatively correlated with withdrawal (r=-0.146, P<0.05) . Conclusion: Most nurses in the emergency treatment room adopt the mature coping style. Their subjective well-being and coping style vary with different ages, nursing years, professional titles, and education levels, and the subjective well-being is relatively low.

RNA interference-aided knockdown of a putative saccharopine dehydrogenase leads to abnormal ecdysis in the brown planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae).

The brown planthopper Nilaparvata lugens is a serious phloem-feeding pest of rice in China. The current study focuses on a saccharopine dehydrogenase (SDH) that catalyzes the penultimate reaction in biosynthesis of the amino acid lysine (Lys), which plays a role in insect growth and carnitine production (as a substrate). The protein, provisionally designated as NlylsSDH [a SDH derived from yeast-like symbiont (YLS) in N. lugens], had a higher transcript level in abdomens, compared with heads, wings, legs and thoraces, which agrees with YLS distribution in N. lugens. Ingestion of Nlylssdh targeted double-stranded RNA (dsNlylssdh) for 5, 10 and 15 days decreased the mRNA abundance in the hoppers by 47, 70 and 31%, respectively, comparing with those ingesting normal or dsegfp diets. Nlylssdh knockdown slightly decreased the body weights, significantly delayed the development of females, and killed approximately 30% of the nymphs. Moreover, some surviving adults showed two apparent phenotypic defects: wing deformation and nymphal cuticles remained on tips of the legs and abdomens. The brachypterours/macropterours and sex ratios (female/male) of the adults on the dsRNA diet were lowered compared with the adults on diets without dsRNA. These results suggest that Nlylssdh encodes a functional SDH protein. The adverse effect of Nlylssdh knockdown on N. lugens implies the importance of Lys in hopper development. This study provides a proof of concept example that Nlylssdh could serve as a possible dsRNA-based pesticide for planthopper control.

Effect of increased levels of adiponectin by administration of the adeno vector rAAV2/1-Acrp30 on glucose, lipid metabolism and ultrastructure of the aorta in Goto-Kakizaki rats with arteriosclerosis.

BACKGROUND: We used recombinant adeno-associated virus vector of adiponectin (AAV2/1-Acrp30) to study the effects of increased levels of adioponectin (by the administration of rAAV2/1-Acrp30) on arteriosclerosis, glucose and lipid metabolism in Goto-Kakizaki (GK) rats with arteriosclerosis. METHODS: Thirty GK rats with arteriosclerosis were divided into 3 equal groups: control group 1, control group 2 and the rAAV2/1-Acrp30-administered group. Saline, virus vector or rAAV2/1-Acrp30 (10 12 ng/ml) vector genomes administered to the rats in the corresponding group by intramuscular injection to the posterior limb by single administration, respectively. After 8 weeks, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated haemoglobin, serum insulin, serum total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein were measured in each group, and the ultrastructure of the aorta was seen by light and electron microscopy. RESULTS: Compared with control groups 1 and 2, in the rAAV2/1-Acrp30 group, there was a decrease in urine volume, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated haemoglobin, serum total cholesterol, triglycerides and low-density lipoprotein, and an increase in body weight and high-density lipoprotein (p< 0.05), while the level of serum insulin was not changed (p>0.05). Ultrastructure studies of the aorta showed that aortosclerosis in the rAAV2/1-Acrp30-administered group was less, and fewer lipid droplet vacuoles were seen in the vascular endothelial cytoplasm. Also various cell organelles and internal elastic lamina were seen, and there was no formation of lipid droplet and foam cells in the cytoplasm of the media of the smooth muscle. CONCLUSION: Adiponectin could improve blood glucose and lipid parameters and decrease atherosclerosis in the aorta of GK rats.

[Identification of Chinese herbs in the Qing Royals--Fu Shen and Fu Shen Mu].

The use of Fu Shen and Fu Shen Mu as medicines has had a long history. Today Fu Shen is still taken as bulk medicinal materials, whereas Fu Shen Mu had disappeared in the medical market. Fu Shen, Yun Fu Shen, Bai Fu Shen, and Bao Mu Fu Shen were used in clinical application in the Qing Royals. Bai Fu Shen and Fu Shen Mu are still kept as speciment in the Palace Museum today. It was found that Bai Fu Shen in the Qing Royals was the same as Fu Shen after peeling and pine roots recorded in the herbal literatures of the Ming and Qing dynasties, with their character tests and historical analysis. It can be inferred that Fu Shen, Yun Fu Shen and Bai Fu Shen recorded in the Qing Royals were actually Fu Shen, with pine roots in sclerotia and after peeling and pine roots removed in processing. Bao Mu Fu Shen and Bao Fu Shen should refer to Fu Shen with pine roots. Fu Shen Mu should mean Fu Shen without white sclerotia and peel during processing. Fu Shen, currently used clinically, is Bao Mu Fu Shen in the Qing Dynasty. Fu Shen distinguishes greatly from Fu Shen Mu in their effects. Such identification and analysis of herbs provides a way of thinking for further hurb studies of the Qing Dynasty.

Chinese herbal medicine combined with tadalafil for erectile dysfunction: a systematic review and meta-analysis.

BACKGROUND: Erectile dysfunction (ED) is a tough problem in medicine. This article aims to provide the latest evidence for the efficacy and safety of traditional Chinese medicine (TCM) combined with tadalafil in treatment of erectile dysfunction. METHODS: All randomized controlled trials that Chinese herbal medicine combined with tadalafil for erectile dysfunction were included in databases of China National Knowledge Infrastructure (CNKI), Wanfang, Weip Database, China Biology Medicine disc (CBM), MEDLINE, EMBASE, and Cochrane Library. The quality of the included articles was evaluated using Cochrane Reviewer's Handbook 5.3, and meta-analysis was performed using Stata 13.1. RESULTS: A total of 11 studies including 451 cases in the treatment group and 452 cases in the control group were obtained. Compared with tadalafil alone, meta-analysis suggests there were statistically significant differences in International Index of Erectile Function-5 (IIEF-5), effective rate, Sexual Encounter Profile questions 2 and 3 (SEP-Q2, SEP-Q3) between traditional Chinese medicine combined with tadalafil, and no statistically significant differences in side effects between the two groups. All included studies were tested for publication bias, and the results indicated that there was no significant bias. Two of the articles mentioned the scheme that traditional Chinese medicine combined with low-dose tadalafil for erectile dysfunction by down stairs. CONCLUSION: Traditional Chinese medicine combined with tadalafil has significant efficacy in the treatment of ED with no increase in side effects. The specific implementing regulations and effect of de-escalation therapy still need more long-term, multicenter, randomized, and double-blind clinical trials.

Biodegradation of nonylphenol in soil.

We investigated the effects of various factors (brij 30, brij 35, yeast extract, hydrogen peroxide and compost) on the aerobic degradation of nonylphenol (NP) in soil and characterized the structure of the microbial community in that soil. Residues of NP were measured using gas chromatography-mass spectrometry (GC-MS) and a change of microbial communities was demonstrated using denaturing gradient gel electrophoresis (DGGE). The results showed that Taichung sandy clay loam had higher NP degradation rate than Kaoshiung silty clay. The addition of compost, yeast extract (0.5 mg/l), brij 30 (55 microM), or brij 35 (91 microM) enhanced NP degradation, while the addition of hydrogen peroxide (1.0 mg/l) inhibited its degradation. We also found that the addition of various substrates changed the microbial community in the soils. Cytophaga sp. and Ochrobactrum sp. were constantly dominant bacteria under various conditions in the soil.

Biodegradation of four phthalate esters in sludge.

This study investigated the effects of ultrasonic pretreatment and various treatments on the aerobic degradation of four phthalic acid esters (PAEs) such as diethyl phthalate (DEP), benzyl butyl phthalate (BBP), di-n-butyl phthalate (DBP) and di-(2-ethyl hexyl)phthalate (DEHP) in sludge. The effect on PAE degradation of treating sludge with a 20 min sonication period at a power level of 0.1 W ml(-1) was evaluated. The degradation rates of the four PAEs were DBP>BBP>DEP>DEHP. Degradation rate constants (k(1)) and half-lives (t(1/2)) for the four PAEs (50 mg kg(-1)) ranged from 0.182 to 0.379 day(-1) and 1.8 to 3.8 days, respectively. The optimal pH for PAE degradation in sludge was 7.0 at 30 degrees C. PAE degradation was enhanced by the addition of yeast extract, brij 30 or brij 35 and inhibited by the addition of hydrogen peroxide. Our results show that a combination of ultrasonic pretreatment and biodegradation can effectively remove PAE from sludge.

Hydrogen peroxide preferentially activates capsaicin-sensitive high threshold afferents via TRPA1 channels in the guinea pig bladder.

BACKGROUND AND PURPOSE: There is increasing evidence suggesting that ROS play a major pathological role in bladder dysfunction induced by bladder inflammation and/or obstruction. The aim of this study was to determine the effect of H2 O2 on different types of bladder afferents and its mechanism of action on sensory neurons in the guinea pig bladder. EXPERIMENTAL APPROACH: 'Close-to-target' single unit extracellular recordings were made from fine branches of pelvic nerves entering the guinea pig bladder, in flat sheet preparations, in vitro. KEY RESULTS: H2 O2 (300-1000 µM) preferentially and potently activated capsaicin-sensitive high threshold afferents but not low threshold stretch-sensitive afferents, which were only activated by significantly higher concentrations of hydrogen peroxide. The TRPV1 channel agonist, capsaicin, excited 86% of high threshold afferents. The TRPA1 channel agonist, allyl isothiocyanate and the TRPM8 channel agonist, icilin activated 72% and 47% of capsaicin-sensitive high threshold afferents respectively. The TRPA1 channel antagonist, HC-030031, but not the TRPV1 channel antagonist, capsazepine or the TRPM8 channel antagonist, N-(2-aminoethyl)-N-[[3-methoxy-4-(phenylmethoxy)phenyl]methyl]thiophene-2-carboxamide, significantly inhibited the H2 O2 -induced activation of high threshold afferents. Dimethylthiourea and deferoxamine did not significantly change the effect of H2 O2 on high threshold afferents. CONCLUSIONS AND IMPLICATIONS: The findings show that H2 O2 , in the concentration range detected in inflammation or reperfusion after ischaemia, evoked long-lasting activation of the majority of capsaicin-sensitive high threshold afferents, but not low threshold stretch-sensitive afferents. The data suggest that the TRPA1 channels located on these capsaicin-sensitive afferent fibres are probable targets of ROS released during oxidative stress.

Protein kinase C activation contributes to microvascular barrier dysfunction in the heart at early stages of diabetes.

The functional disturbance of microvasculature is recognized as an initiating mechanism that underlies the development of various diabetic complications. Although a causal relationship between microvascular leakage and tissue damage has been well documented in diabetic kidneys and eyes, there is a lack of information regarding the barrier function of coronary exchange vessels in the disease state. The aim of the present study was to evaluate the permeability property of coronary microvessels during the early development of experimental diabetes with a focus on the protein kinase C (PKC)-dependent signaling mechanism. The apparent permeability coefficient of albumin (Pa) was measured in isolated and perfused porcine coronary venules. The administration of high concentrations of D-glucose induced a dose-dependent increase in the Pa value, which was prevented by blockage of PKC with its selective inhibitors bisindolylmaleimide and Goe 6976. More importantly, an elevated basal permeability to albumin was observed in coronary venules at the early onset of streptozotocin-induced diabetes. The hyperpermeability was corrected with bisindolylmaleimide and the selective PKCbeta inhibitor hispidin. Concomitantly, protein kinase assay showed a high PKC activity in isolated diabetic venules. Immunoblot analysis of the diabetic heart revealed a significant subcellular translocation of PKCbetaII and PKCepsilon from the cytosol to the membrane, indicating that the specific activity of these isoforms was preferentially elevated. The results suggest that endothelial barrier dysfunction attributed to the activation of PKC occurs at the coronary exchange vessels in early diabetes.

Critical role of astrocytic interleukin-17 A in post-stroke survival and neuronal differentiation of neural precursor cells in adult mice.

The brain and the immune system interact in complex ways after ischemic stroke, and the long-term effects of immune response associated with stroke remain controversial. As a linkage between innate and adaptive immunity, interleukin-17 A (IL-17 A) secreted from gamma delta (γδ) T cells has detrimental roles in the pathogenesis of acute ischemic stroke. However, to date, the long-term actions of IL-17 A after stroke have not been investigated. Here, we found that IL-17 A showed two distinct peaks of expression in the ischemic hemisphere: the first occurring within 3 days and the second on day 28 after stroke. Our data also showed that astrocyte was the major cellular source of IL-17 A that maintained and augmented subventricular zone (SVZ) neural precursor cells (NPCs) survival, neuronal differentiation, and subsequent synaptogenesis and functional recovery after stroke. IL-17 A also promoted neuronal differentiation in cultured NPCs from the ischemic SVZ. Furthermore, our in vitro data revealed that in primary astrocyte cultures activated astrocytes released IL-17 A via p38 mitogen-activated protein kinase (MAPK). Culture media from reactive astrocytes increased neuronal differentiation of NSCs in vitro. Blockade of IL-17 A with neutralizing antibody prevented this effect. In addition, after screening for multiple signaling pathways, we revealed that the p38 MAPK/calpain 1 signaling pathway was involved in IL-17 A-mediated neurogenesis in vivo and in vitro. Thus, our results reveal a previously uncharacterized property of astrocytic IL-17 A in the maintenance and augment of survival and neuronal differentiation of NPCs, and subsequent synaptogenesis and spontaneous recovery after ischemic stroke.

Biodegradation of nonylphenol in sewage sludge.

We investigated the effects of various factors on the aerobic degradation of nonylphenol (NP) in sewage sludge. NP (5 mg/kg) degradation rate constants (k1) calculated were 0.148 and 0.224 day(-1) for the batch experiment and the bioreactor experiment, respectively, and half-lives (t(1/2)) were 4.7 and 3.1 days, respectively. The optimal pH value for NP degradation in sludge was 7.0 and the degradation rate was enhanced when the temperature was increased and when yeast extract (5 mg/l) and surfactants such as brij 30 or brij 35 (55 or 91 microM) were added. The addition of aluminum sulfate (200 mg/l) and hydrogen peroxide (1 mg/l) inhibited NP degradation within 28 days of incubation. Of the microorganism strains isolated from the sludge samples, we found that strain CT7 (identified as Bacillus sphaericus) manifested the best degrading ability.

Anaerobic degradation of nonylphenol in sludge.

We investigated the effects of various factors on the anaerobic degradation of nonylphenol (NP) in sludge. NP (5 mg/l) anaerobic degradation rate constants were 0.029 1/day for sewage sludge and 0.019l/day for petrochemical sludge, and half-lives were 23.9 days and 36.5 days respectively. The optimal pH for NP degradation in sludge was 7 and the degradation rate was enhanced when the temperature was increased. The addition of yeast extract (5 mg/l) or surfactants such as brij 30 or brij 35 (55 or 91 microM) also enhanced the NP degradation rate. The addition of aluminum sulfate (200 mg/l) inhibited the NP degradation rate within 84 days of incubation. The high-to-low order of degradation rates was: sulfate-reducing conditions>methanogenic conditions>nitrate-reducing conditions. Sulfate-reducing bacteria, methanogen, and eubacteria are involved in the degradation of NP, sulfate-reducing bacteria being a major component of sludge.

Anaerobic degradation of diethyl phthalate, di-n-butyl phthalate, and di-(2-ethylhexyl) phthalate from river sediment in Taiwan.

We investigated anaerobic degradation rates for three phthalate esters (PAEs), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), and di-(2-ethylhexyl) phthalate (DEHP), from river sediment in Taiwan. The respective anaerobic degradation rate constants for DEP, DBP, and DEHP were observed as 0.045, 0.074, and 0.027 1/day, with respective half-lives of 15.4, 9.4, and 25.7 days under optimal conditions of 30 degrees C and pH7.0. Anaerobic degradation rates were enhanced by the addition of the surfactants brij 35 and triton N101 at a concentration of 1 critical micelle concentration (CMC), and by the addition of yeast extract. Degradation rates were inhibited by the addition of acetate, pyruvate, lactate, FeCl3, MnO2, NaCl, heavy metals, and nonylphenol. Our results indicate that methanogen, sulfate-reducing bacteria, and eubacteria are involved in the degradation of PAEs.

Inhibition of interleukin-6 abolishes the promoting effects of pair housing on post-stroke neurogenesis.

Interleukin-6 (IL-6) has been shown to promote post-stroke angiogenesis and long-term functional recovery; however, whether IL-6 could promote post-stroke neurogenesis remains unclear. This study aims to investigate the effects of IL-6 on neurogenesis after ischemic stroke. We also investigated whether pair housing (PH) could improve the experimental stroke outcome through IL-6. Transient middle cerebral artery occlusion (tMCAO) was induced in mice treated with recombinant IL-6 (rIL-6) or anti-IL-6 neutralizing antibodies (anti-IL-6 mAbs). Another set of mice were pair-housed (PH; male and ovariectomized female) for 2weeks, subjected to tMCAO and then assigned to a housing condition (isolated or PH). Pair-housed mice were treated with anti-IL-6 mAbs. Behavioral assessments were made 3days before tMCAO and after 28 days of reperfusion. Neural progenitor cells (NPCs) isolated from ipsilateral subventricular zone (SVZ) at 14 days post-ischemia were treated with rIL-6 plus soluble IL-6 receptor (sIL-6R). The effects of IL-6 on the proliferation and differentiation of NPCs were examined in vivo and in vitro. The role and mechanism of IL-6 in PH-mediated enhancement of NPC proliferation and functional recovery were investigated in vivo. We found that anti-IL-6 mAbs significantly reduced the proliferation and neuronal differentiation of NPCs in the ipsilateral SVZ, as well as functional recovery; whereas rIL-6 conferred the opposite effects. PH significantly promoted NPC proliferation and functional recovery compared with socially isolated cohorts; blockade of IL-6 with anti-IL-6 mAbs prevented this promoting effect. In conclusion, our results suggest that IL-6 is an important mediator of social interaction on neurogenesis and long-term functional recovery after ischemic stroke.

Novel spinal pathways identified by neuronal c-Fos expression after urethrogenital reflex activation in female guinea pigs.

Pudendal nerve-spinal pathways are involved in urethrogenital sensation, pain and sexual activity. However, details of these pathways and their modulation are unclear. We examined spinal pathways activated by the urethrogenital reflex (UGR) and visualized by c-Fos immunoreactivity in reflexly activated neurons within spinal cord. In anesthetized female guinea pigs, a balloon was inserted into the urethra and inflated with short-repeat or long-continuous distension to activate the UGR. A second balloon recorded reflex contractions of the vagina and uterus. Two control groups had either no balloon or a vaginal balloon (VB) only. Ninety minutes after UGR activation, c-Fos immunoreactivity in L3 and S2 spinal segments was examined. Reflex activated c-Fos immunoreactivity also was investigated in some animals with acute spinal transections at either L4 or T12 levels. There was no significant difference in spinal c-Fos expression between the control groups. Short-repeat distension reliably induced a UGR and a two- to threefold increase in c-Fos-expressing neurons throughout dorsal, intermediate and lateral spinal gray matter at S2 and about twofold increase in superficial dorsal horn at L3. T12 transection had little effect on c-Fos expression at either spinal level. However, after L4 transection, UGR generation was associated with a four- to sixfold increase in c-Fos-expressing neurons in lateral horn (LH) and central canal areas at S2, and but only 20-30% increase at L3. Thus, UGR activates preganglionic neurons projecting to pelvic viscera in both sacral and lumbar spinal cord. The reflex also must activate ascending and descending spinal inhibitory circuits that suppress c-Fos-expression in neurons at both sacral and lumbar spinal levels.