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Introduction: Underimmunization of CHD children is a public health concern in China. This study aimed to analyze the vaccination status of CHD children to provide additional evidence on optimal vaccination strategies and to make suggestions to promote appropriate vaccination services for these children., Methods: This cross-sectional study evaluated 155 CHD children who received at least one vaccine at Peking University First Hospital. Vaccine-specific immunization rates were calculated. A telephone questionnaire survey was conducted that covered the following: the prognosis, reasons for delayed vaccinations and getting vaccination in the hospital. All statistical analyses were performed using the SPSS version 22 software., Results: The left-to-right shunt group involved 138 children, while the other type CHD group involved 17. The vaccination rate was the highest for MPSV-AC (87.1%) and the lowest for DTaP (40.1%). The most frequent reason for vaccination in the hospital was refusal from community health centers (61.5%). No participant reported vaccine-related adverse effects., Conclusions: The age-appropriate vaccine-specific immunization rates in CHD children are low, with the lowest for DTaP. Refusal of community health centers was the primary reason. Our findings support that clinically stable CHD children may be safely vaccinated on a schedule similar to that of ordinary children in China., Impact: From our investigation, we found that the age-appropriate vaccine-specific immunization rates in children with CHD in China are low, with the lowest for diphtheria and tetanus toxoid and acellular pertussis. Refusal of community health centers to vaccinate was the primary reason for the low rates. We believe our study provides additional evidence on optimal vaccination strategies for children with CHD and it can be used to develop strategies to promote appropriate vaccination services for these children., (© 2022. The Author(s).)

Objective: To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options., Methods: The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed., Results: A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4－18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs . 28.08%, χ 2 = 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS., Conclusion: POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.

The normal feeling of touch is vital for nearly every aspect of our daily life. However, touching is not always felt as touch, but also abnormally as pain under numerous diseased conditions. For either mechanistic understanding of the faithful feeling of touch or clinical management of chronic pain, there is an essential need to thoroughly dissect the neuropathological changes that lead to painful touch or tactile allodynia and their corresponding cellular and molecular underpinnings. In recent years, we have seen remarkable progress in our understanding of the neural circuits for painful touch, with an increasing emphasis on the upstream roles of non-neuronal cells. As a highly specialized form of axon ensheathment by glial cells in jawed vertebrates, myelin sheaths not only mediate their outstanding neural functions via saltatory impulse propagation of temporal and spatial precision, but also support long-term neuronal/axonal integrity via metabolic and neurotrophic coupling. Therefore, myelinopathies have been implicated in diverse neuropsychiatric diseases, which are traditionally recognized as a result of the dysfunctions of neural circuits. However, whether myelinopathies can transform touch into pain remains a long-standing question. By summarizing and reframing the fragmentary but accumulating evidence so far, the present review indicates that sensory root demyelination represents a hitherto underappreciated neuropathological change for most neuropathic conditions of painful touch and offers an insightful window into faithful tactile sensation as well as a potential therapeutic target for intractable painful touch., (© 2021 Wiley Periodicals LLC.)

Background: We aimed to explore predictive measures for intravenous immunoglobulin (IVIG) resistance in children with Kawasaki disease (KD)., Methods: Patients diagnosed with KD were enrolled in this study. Univariate analysis and multiple logistic regression were utilized to analyze the clinical features and laboratory results prior to IVIG-treatment of the two groups. Independent predictors of IVIG resistance were analyzed, and a predictive model for KD children with IVIG resistance was constructed., Results: A total of 277 children with KD, 180 boys and 97 girls, aged 2-128 (median 23) months, were enrolled in the study. Compared with the IVIG-responsive group, the IVIG-resistant group had higher levels of the peripheral neutrophil count, mean platelet volume, mean platelet volume-to-lymphocyte ratio and C-reactive protein, and total serum bilirubin, but lower levels of peripheral lymphocyte count, serum albumin and serum prealbumin. Age (in months), peripheral neutrophil count, lymphocyte count and mean platelet volume and serum albumin were independent indicators for IVIG resistance by multivariate logistic regression analysis. A logistic regression model and a scoring system were set up, where cut-off values of - 0.46 and 6.5 points yielded sensitivities of 83.9% and 77.4%, and specificities of 74.8% and 61.0%, respectively. The areas under the curve (AUC) were 0.808 in the logistic regression model, and 0.750 in the scoring system., Conclusion: Our model for predicting IVIG-resistant children with KD, involving age (months), peripheral neutrophil count, lymphocyte count and mean platelet volume and serum albumin prior to IVIG-treatment, is helpful for clinical prediction of children with IVIG-resistant KD.

Nerve injury-induced chronic pain has been an urgent problem for both public health and clinical practice. While transition to chronic pain is not an inevitable consequence of nerve injuries, the susceptibility/resilience factors and mechanisms for chronic neuropathic pain after nerve injuries still remain unknown. Current preclinical and clinical studies, with certain notable limitations, have shown that major histocompatibility complex class II-restricted T helper (Th) cells is an important trigger for nerve injury-induced chronic tactile allodynia, one of the most prevalent and intractable clinical symptoms of neuropathic pain. Moreover, the precise pathogenic neuroimmune interfaces for Th cells remain controversial, not to mention the detailed pathogenic mechanisms. In this review, depending on the biology of Th cells in a neuroimmunological perspective, we summarize what is currently known about Th cells as a trigger for chronic tactile allodynia after nerve injuries, with a focus on identifying what inconsistencies are evident. Then, we discuss how an interdisciplinary perspective would improve the understanding of Th cells as a trigger for chronic tactile allodynia after nerve injuries. Finally, we hope that the expected new findings in the near future would translate into new therapeutic strategies via targeting Th cells in the context of precision medicine to either prevent or reverse chronic neuropathic tactile allodynia.

Background: Vasovagal syncope (VVS) is common in children and greatly affect both physical and mental health. But the mechanisms have not been completely explained. This study was designed to analyze the gut microbiota in children with VVS and explore its clinical significance., Methods: Fecal samples from 20 VVS children and 20 matched controls were collected, and the microbiota were analyzed by 16S rRNA gene sequencing. The diversity and microbiota compositions of the VVS cases and controls were compared with the independent sample t test or Mann-Whitney U test. The correlation between the predominant bacteria and clinical symptoms was analyzed using Pearson or Spearman correlation test., Results: No significant differences in diversity were evident between VVS and controls (P > 0.05). At the family level, the relative abundance of Ruminococcaceae was significantly higher in VVS children than in controls (median [Q1, Q3]: 22.10% [16.89%, 27.36%] vs. 13.92% [10.31%, 20.18%], Z = -2.40, P < 0.05), and LEfSe analysis revealed Ruminococcaceae as a discriminative feature (linear discriminant analysis [LDA] score > 4, P < 0.05). The relative abundance of Ruminococcaceae in VVS patients was positively correlated with the frequency of syncope (r = 0.616, P < 0.01). In terms of its correlation with hemodynamics, we showed that relative abundance of Ruminococcaceae was negatively correlated with the systolic and diastolic pressure reduction at the positive response in head-up tilt test (HUTT; r = -0.489 and -0.448, all P < 0.05), but was positively correlated with the mean pressure drop and decline rate (r = 0.489 and 0.467, all P < 0.05) as well as diastolic pressure drop and decline rate at the HUTT positive response (r = 0.579 and 0.589, all P < 0.01) in VVS patients., Conclusion: Ruminococcaceae was the predominant gut bacteria and was associated with the clinical symptoms and hemodynamics of VVS, suggesting that gut microbiota might be involved in the development of VVS.

Multidrug resistance (MDR) is a major cause of failure in cancer treatment, in which the overexpression of P-glycoprotein (Pgp) plays a crucial role. Herein, a novel class of ocotillol-type amide derivatives has been designed, synthesized, and evaluated for their ability to reverse MDR. The structure-activity relationship of the reversal activity was analyzed. Ten compounds showed promising chemo-reversal ability, among which the 24R-ocotillol-type amide derivative 6c with an N-Boc-hexanoyl unit exhibited the most potency in reversing paclitaxel resistance in KBV cells. Compound 6c could inhibit Pgp-mediated rhodamine123 efflux function via stimulating Pgp-ATPase activity and exhibited high binding affinity with Pgp in molecular docking studies. Importantly, compound 6c enhanced the efficacy of paclitaxel against KBV cancer cell-derived xenograft tumors in nude mice after oral administration. These results indicate that ocotillol-type amide derivatives are promising lead compounds for overcoming MDR in cancer., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Hederagenin is a naturally occurring pentacyclic triterpenoids compound with multiple pharmacological activities. We recently showed that H6, a synthetic derivative of hederagenin, could enhance the anticancer activity of paclitaxel in drug-resistant cells in vitro and in vivo, but showed poor solubility. With the aim of improving the drug resistant reversal activity of H6, here we designed and synthesized a series of novel H6 analogues. Our results showed that compound 10 at the concentration of 5 μM significantly enhanced the cytotoxicity of paclitaxel to drug-resistant KBV cells and sensitized cells to paclitaxel in arresting cells in G 2 /M phase and inducing apoptosis. We found that compound 10 might block the drug efflux of P-gp via stimulating P-gp ATPase activity. Importantly, compound 10 enhanced the efficacy of paclitaxel against KBV cancer cell-derived xenograft tumors. Finally, we summarized a preliminary structure-activity relationship of hederagenin by the drug resistant reversal activity of H6 analogues in vitro and compound 10 and H6in vivo. This study highlights the importance of nitrogen-containing derivatives of hederagenin C-28 in the development of novel drug resistance reversal agents., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Selective serotonin reuptake inhibitors (SSRIs) have developed as novel antidepressants and have been determined to possess higher efficacy and less adverse effects compared to other antidepressants. Our previous studies have showed that LPM570065, a new potent TRI, is relatively nontoxic in acute, subchronic toxicity and genotoxicity evaluations. In the current study, toxicity of LPM570065 was further evaluated on the fertility and early embryonic development in Sprague-Dawley rats. A total of 264 rats were treated with various concentrations of LPM570065 (30 mg/kg, 100 mg/kg, and 300 mg/kg) or used as control. Females rats were treated for two consecutive weeks, followed by mating via cohabitation up to the 7th gestation day (GD). The male rats were treated for four consecutive weeks, which were followed by first mating with treated female rats. Then, all males were treated up to the 9th week and followed by second mating with non-treated female rats, and were sacrificed. All surviving pregnant females were euthanized on GD 15. We evaluated the following parameters, namely, mortality, toxicity symptoms, body weight, amount of food consumed, sexual cycle, mating behavior, pregnancy, sperm production, gross necropsy, and weight of organs. Excessive salivation was observed post treatment in nearly all females and males in the 100 and 300 mg/kg LPM570065 treatment groups. Body weight gain was decreased in gravid rats treated with 300 mg/kg LPM570065 during GD 0-6 (P < 0.05). The application of 300 mg/kg of LPM57006 to male rats induced a decrease in implantation sites and lower fertility rates (P < 0.05). However, sperm concentration and count were higher in the LPM570065-treated groups (30 mg/kg, 100 mg/kg, and 300 mg/kg) compared to the controls. Moreover, duration of mating significantly decreased to 37.5% after nine weeks of LPM570065 treatment at a concentration of 300 mg/kg (P < 0.05). In conclusion, the no observable adverse effect level (NOAEL) was established at 100 mg/kg and 300 mg/kg for female and male rats, respectively. The NOAEL for fertility and early embryonic development was established at 300 mg/kg and 100 mg/kg for female and male rats, respectively., (Copyright © 2018. Published by Elsevier Inc.)

In the current study, to support the safety of LPM570065 as a new potent triple reuptake inhibitors (TRIs), LPM570065 was investigated through a single- and 13-week repeated-dose oral toxicity evaluation and mutagenicity assays. In an acute toxicity evaluation, Sprague-Dawley (SD) rats were single administration at dose of 500, 1000 and 2000 mg/kg. The results suggested that two (2/20) and seven (7/20) animals were died in the 1000 and 2000 mg/kg group, respectively. In contrast, there were no treatment-related effects at a dose of 500 mg/kg. In a 13-week toxicity evaluation, SD rats were given 30, 100, or 300 mg/kg LPM570065 for 13 successive weeks and then allowed a 4-week recovery period. Impermanent salivation was found at each of the doses, and an impermanent minor body weight decrease was noted in the 300 mg/kg males (P < 0.05). Notably, serum prolactin levels were lowered by 43.25% and 78.65% in the male rats in 100 and 300 mg/kg groups, respectively (P < 0.05). Further, the serum testosterone was elevated by 37% in the 30 and 100 mg/kg males. In conclusion, the maximum tolerated dose (MTD) was 500 mg/kg and the lethal dose was 1000 mg/kg in SD rats after a single administration of LPM570065. In 13-week repeated-dose oral toxicity, the no-observed-adverse-effect level (NOAEL) of LPM570065 was greater than 300 mg/kg for rats. Moreover, LPM570065 was not mutagenic or clastogenic. According to this result it can be concluded that the MTD of LMP570065 is approximately up to 3000 mg/person/day in clinic, and the effects of LMP570065 on sexual function also should be considered., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Antigen-specific and MHCII-restricted CD4+ αβ T cells have been shown or suggested to play an important role in the transition from acute to chronic mechanical allodynia after peripheral nerve injuries. However, it is still largely unknown where these T cells infiltrate along the somatosensory pathways transmitting mechanical allodynia to initiate the development of chronic mechanical allodynia after nerve injuries. Therefore, the purpose of this study was to ascertain the definite neuroimmune interface for these T cells to initiate the development of chronic mechanical allodynia after peripheral nerve injuries., Methods: First, we utilized both chromogenic and fluorescent immunohistochemistry (IHC) to map αβ T cells along the somatosensory pathways for the transmission of mechanical allodynia after modified spared nerve injuries (mSNIs), i.e., tibial nerve injuries, in adult male Sprague-Dawley rats. We further characterized the molecular identity of these αβ T cells selectively infiltrating into the leptomeninges of L4 dorsal roots (DRs). Second, we identified the specific origins in lumbar lymph nodes (LLNs) for CD4+ αβ T cells selectively present in the leptomeninges of L4 DRs by two experiments: (1) chromogenic IHC in these lymph nodes for CD4+ αβ T cell responses after mSNIs and (2) fluorescent IHC for temporal dynamics of CD4+ αβ T cell infiltration into the L4 DR leptomeninges after mSNIs in prior lymphadenectomized or sham-operated animals to LLNs. Finally, following mSNIs, we evaluated the effects of region-specific targeting of these T cells through prior lymphadenectomy to LLNs and chronic intrathecal application of the suppressive anti-αβTCR antibodies on the development of mechanical allodynia by von Frey hair test and spinal glial or neuronal activation by fluorescent IHC., Results: Our results showed that during the sub-acute phase after mSNIs, αβ T cells selectively infiltrate into the leptomeninges of the lumbar DRs along the somatosensory pathways responsible for transmitting mechanical allodynia. Almost all these αβ T cells are CD4 positive. Moreover, the temporal dynamics of CD4+ αβ T cell infiltration into the lumbar DR leptomeninges are specifically determined by LLNs after mSNIs. Prior lymphadenectomy to LLNs specifically reduces the development of mSNI-induced chronic mechanical allodynia. More importantly, intrathecal application of the suppressive anti-αβTCR antibodies reduces the development of mSNI-induced chronic mechanical allodynia. In addition, prior lymphadenectomy to LLNs attenuates mSNI-induced spinal activation of glial cells and PKCγ + excitatory interneurons., Conclusions: The noteworthy results here provide the first evidence that CD4+ αβ T cells selectively infiltrate into the DR leptomeninges of the somatosensory pathways transmitting mechanical allodynia and contribute to the transition from acute to chronic mechanical allodynia after peripheral nerve injuries.

Objective: To deepen our understanding of Methylmalonic aciduria (MMA) associated pulmonary hypertension (PH) by analyzing the characteristics of clinical presentation, pulmonary high resolusion CT(HRCT), treatment response and gene mutation., Methods: This study includes 15 cases of pediatric patients with MMA associated PH diagnosed and treated in Peking University First Hospital pediatric department between May 2012 and May 2016 with symptoms of PH as their leading presentation. Clinical symptoms and signs were recorded, Routine blood laboratory examinations was done including arterial blood gas analysis. Plasma total homocysteine (Hcy) and brain natriuretic peptide(BNP) level were measured. MMA gene mutation was analyzed. Chest HRCT was done in most of the patients. Standard treatment strategy to MMA and PH was given and follow up study was done, and the related literature was reviewed. Statistical analysis was done. The diagnosis of MMA was made by methylmalonic acid level >100 times the normal value in the urine. The diagnosis of PH was made by pulmonary arterial systolic pressure (PASP)>40 mmHg, which was estimated by the measurement of tricuspid regurgitation velocity through Doppler Echocardiography., Results: (1) Patient characteristics: There were 10 male and 5 female patients diagnosed as MMA associated PH, aged 0.5 to 13.8 years, with an average of (5.0±4.3) years. The age of onset of PH was (3.7±3.5) years, with an early onset type MMA in 5 cases and late-onset type in 10 cases. (2) Clinical presentation: Among the 15 cases of MMA, the first symptoms were associated with PH in 10 cases, so PH and MMA were diagnosed at the same time, and PH was diagnosed 3 to 72 months post MMA presentation in the other 5 cases. The main presentations of PH were techypnea/dyspnea and cyanosis in 11 cases each, weakness and fatigue on exertion in 6 cases, and edema in 4 cases. PH WHO functional classification (WHO FC) was Class II in 4 , Class III in 5 and Class VI in 6 cases, with an average of Class 3.1±0.8. Multi-system involvements were common with the highest frequency in the kidney (14 cases). Macrocytic anemia was present in 8 cases and sub-clinical hypothyroidism in 5 cases, and mild to moderate mental retardation in 4 cases. (3) Laboratory examination: PASP of the 15 patients was from 49 to 135 mmHg, with an average of (90.3±23.9) mmHg. Total blood Hcy level was severely elevated to (121.2±48.2) μmol/L (range: 35.0-221.0 μmol/L), and Hcy >100 μmol/L within 11 cases. Plasma BNP level was also elevated, median 794 ng/L (range: 21.0-4 995.0 ng/L) with 12 cases >300 ng/L. Blood gas analysis showed low arterial blood oxygen saturation between 70% and 94%, with an average of 81.4%±8.4%. (4) Chest HRCT: chest HRCT showed a diffuse ground-glass centrilobular nodular opacities with septal line thickening in the lungs in 9 cases, and with associated mediastinal lymph node enlargement in 1 case, which indicated pulmonary veno-occlusive disease (PVOD), a rare type of pulmonary arterial hypertension (PAH). There was lung infection or edema in 3 cases, and interstitial infiltration and mesh-like feature in other 3 cases, which was inferred to interstitial lung disease. (5) Gene mutation: Genetic testing was done in 10 cases, totally 5 reported disease-causing mutations were found. There were 100% presence of MMACHC c.80A>G mutation in all the 10 patients tested, with the allelic genes of c.609G>A mutation in 6 patients, including a sister and a brother from the same parents. (6) Treatment and follow up: Intramuscular hydroxocobalamin or vitamin B12 was given to all of the patients, together with betaine, levocarnidtine, folinic acid and vitamin B6. According to the severity of PH, single or combined PAH targeted drugs was given to 11 cases. By an average of (20.0±13.5) days of in-hospital treatment in 13 patients (excepting 1 case treated as outpatient), symptoms remarkably resolved, WHO FC reduced to an average of Class 2.4±0.9, PASP dropped to (69.4±21.3) mmHg, and plasma Hcy and BNP level were decreased to (74.9±25.9) μmol/L and (341.6±180.2) ng/L, respectively. The above values all reached statistical significance (P<0.05) compared with each related value before treatment. There were 2 patients who expired during hospitalization despite of treatment. At the end of 3 months' follow up, all of the 13 patients disposed oxygen, and PASP significantly dropped to 38.7±7.9 mmHg, and plasma BNP returned to normal, but plasma Hcy level showed no further decline. At the last follow up of 27.5±19.0 (range: 11-64) months, all the patients' PASP remained normal except for the 13.8-year-old boy with 6 years-long history of MMA and almost 3.6 years' history of PH still having PASP 58 mmHg., Conclusion: PH is a severe complication of MMA combined type, especially cblC type, it is more often happens in late-onset type of male patients and can be the first and leading manifestations of MMA. Its clinical symptoms are urgent and severe, characterized by tachypnea/dyspnea and cyanosis, and sometimes right heart failure, hypoxemia is usually present, chest HRCT is often indicative of PVOD, lung edema and interstitial lung disease may occur. Rapid diagnosis and targeted treatment of MMA with appropriate anti-PAH medication can reverse PH and save life. MMACHC gene c.80A>G mutation may be the hot point of MMA cblC type associated PH.

Fluorescent immunolabeling and imaging in free-floating thick (50-60 μm) tissue sections is relatively simple in practice and enables design-based non-biased stereology, or 3-D reconstruction and analysis. This method is widely used for 3-D in situ quantitative biology in many areas of biological research. However, the labeling quality and efficiency of standard protocols for fluorescent immunolabeling of these tissue sections are not always satisfactory. Here, we systematically evaluate the effects of raising the conventional antibody incubation temperatures (4°C or 21°C) to mammalian body temperature (37°C) in these protocols. Our modification significantly enhances the quality (labeling sensitivity, specificity, and homogeneity) and efficiency (antibody concentration and antibody incubation duration) of fluorescent immunolabeling of free-floating thick tissue sections.

After peripheral nerve damage, injured or stressed primary sensory neurons (PSNs) transmitting pathological pain (pathopain) sensitize central nervous system (CNS) neural circuits and determine behavioral phenotypes of peripheral neuropathic pain (PNP). Therefore, phenotypic profiling of pathopain-transmitting PSNs is vital for probing and discovering PNP conditions. Following peripheral nerve injuries (PNIs), PNP might be potentially transmitted by distinct classes of damaged or stressed PSNs, such as axotomized PSNs without regeneration (axotomy-non-regenerative neurons), axotomized PSNs with accurate regeneration (axotomy-regenerative neurons), and spared intact PSNs adjacent to axotomized neurons (axotomy-spared neurons). Both axotomy-non-regenerative neurons and axotomy-spared neurons have been definitely shown to participate in specific PNP transmission. However, whether axotomy-regenerative neurons could transmit PNP with unique features has remained unclear. Recent studies in rodent models of axonotmesis have clearly demonstrated that axotomy-regenerative neurons alone transmit persistent pathological pain with unique behavioral phenotypes. In this review, we exclusively review this novel category of PNP, reasonably term it 'regenerative peripheral neuropathic pain', and finally discuss its potential clinical significance as a new therapeutic dimension for PNIs beyond nerve regeneration.

Schwann cell migration, including collective migration and chemotaxis, is essential for the formation of coordinate interactions between Schwann cells and axons during peripheral nerve development and regeneration. Moreover, limited migration of Schwann cells imposed a serious obstacle on Schwann cell-astrocytes intermingling and spinal cord repair after Schwann cell transplantation into injured spinal cords. Recent studies have shown that mature brain-derived neurotrophic factor, a member of the neurotrophin family, inhibits Schwann cell migration. The precursor form of brain-derived neurotrophic factor, proBDNF, was expressed in the developing or degenerating peripheral nerves and the injured spinal cords. Since "the yin and yang of neurotrophin action" has been established as a common sense, proBDNF would be expected to promote Schwann cell migration. However, we found, in the present study, that exogenous proBDNF also inhibited in vitro collective migration and chemotaxis of RSC 96 cells, a spontaneously immortalized rat Schwann cell line. Moreover, proBDNF suppressed adhesion and spreading of those cells. At molecular level, proBDNF inhibits F-actin polymerization and focal adhesion dynamics in cultured RSC 96 cells. Therefore, our results suggested a special case against the classical opinion of "the yin and yang of neurotrophin action" and implied that proBDNF might modulate peripheral nerve development or regeneration and spinal cord repair through perturbing native or transplanted Schwann cell migration., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: To determine the effect of early systemic administration of IL-10 on peripheral neuropathic pain induced by tibial nerve permanent transection [modified spared nerve injury (mSNI)]in adult rats., Methods: Male adult Sprague-Dawley (SD) rats (ten-week old, 250-300 g) with mSNI were randomly divided into mSNI, sham-operated, IL-10 intervention (intraperitoneal injection), PBS intervention (intraperitoneal injection) groups, each containing six rats. Intraperitoneally injections (IL-10 or PBS) were given immediately after surgeries for a single regime with a dosage of 500 uL (0.1 mg/mL). Plantar test, von Frey hairs test, pinprick test and acetone test were performed before and after tibial nerve injuries (0 d, 4/5 d, 7/8 d, 14/15 d) to evaluate region-specific pain responses of the rats on the plantar sural and saphenous skin territories of ipsilateral and contralateral hindpaws. The hindpaw position (on 8 d) of six additional rats with standard SNI was compared with those with mSNI., Results: The rats with standard SNI showed an eversion posture of hindpaws, more prominent than those with mSNI. Region-specific pathological pain evoked by mechanical and thermal stimuli on the sural and saphenous skin territories of the plantar surfaces of rat hindpaws was demonstrated on the ipsilateral rather than contralateral hindpaws. This effect was shown in the rats with mSNI but not in those with sham operations. Compared with PBS, early intraperitoneal injection of IL-10 significantly and persistently attenuated either allodynia or hyperalgesia in the rats with mSNI., Conclusions: Tibial nerve permanent transection models of adult rats can be used as a simple but useful rodent model of peripheral neuropathic pain. Early systemic administration of IL-10 impairs the pathogenesis of neuropathic pain induced by tibial nerve injuries.

Objectives: To investigate the effect of helminth-derived immunomodulatory glycan lacto-N-fucopentaose3(LNFP3) on the pathogenesis of neuropathic pain and spinal glial activation in the corresponding time windows after adult rat tibial nerve permanent transection (modified spared nerve injury, mSNI)., Methods: Ten weeks old male adult Sprague-Dawley (SD) rats weighing 250-300 g were randomly grouped into four groups: sham-operated group ( n =6), mSNI group ( n =6), mSNI plus bovine serum albumin (BSA) group ( n =12) and mSNI plus LNFP3 group ( n =12). Rats were subjected to surgical operation or sham operation on the right tibial nerves and were intraperitoneal injected BSA or LNEP3-BSA conjugates by the group design. Animals from each group ( n =6 per group) were subjected to the plantar test,von Frey hairs test, pinprick test and acetone test for critical evaluation of region-specific pain responses on the plantar sural and saphenous skin territories of ipsilateral and contralateral hindpaws after injuries. Transverse frozen sections of L3-4 spinal cords from the remaining animals of mSNI plus BSA group and mSNI plus LNFP3 group 7 and 14 d after injury ( n =3 for each time point per group)were prepared and subjected to immunofluorescent staining of microglia/macrophage marker [cluster of differentiation molecule 11b (CD11b)] and astrocyte marker [glial fibrillary acidic protein (GFAP)], for analysis of spinal glial activation., Results: After adult rat mSNI, early systematic administration of LNFP3 significantly but not completely attenuated region-specific pathological pain evoked by mechanical and thermal stimuli on the sural and saphenous skin territories of rat hindpaw plantar surfaces in acute (4/5 d after injuries) and subacute (7/8 d and 14/15 d after injuries) phases. Meanwhile, in the ipsilateral spinal cord dorsal horns, this early systematic treatment inhibited microglia/macrophage activation 7 d after injury and astrocyte activation 7 and 14 d after injury., Conclusions: Early systematic administration of LNFP3 impairs the pathogenesis (acute induction and chronic transition) of neuropathic pain and spinal glial activation in the corresponding time windows after adult rat mSNI.

The real-space resolving of the encapsulated overlayer in the well-known model and industry catalysts, ascribed to the advent of dedicated transmission electron microscopy, enables us to probe novel nano/micro architecture chemistry for better application, revisiting our understanding of this key issue in heterogeneous catalysis. In this review, we summarize the latest progress of real-space observation of SMSI in several well-known systems mainly covered from the metal catalysts (mostly Pt) supported by the TiO2 , CeO2 and Fe3 O4 . As a comparison with the model catalyst Pt/Fe3 O4 , the industrial catalyst Cu/ZnO is also listed, followed with the suggested ongoing directions in the field., (© 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.)

Objective: To investigate the effect of prolonged axon depletion on senescence-associated beta galactosidase (SA-β-gal) expression in Schwann cells (SCs) of adult rats., Methods: Male adult Sprague-Dawley (SD) rats were randomize grouped into sham-operated group and denervation groups for 1 week, 2 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks and 8 weeks. Rats were subjected to right sciatic nerve transection. After particular denervation duration for the distal stumps, animals were anesthetized and perfused. Proximal stumps of 5 mm and distal stumps of 10 mm from injured nerves, and the corresponding segments from the sham groups and contralateral nerves were harvested and prepared for SA-β-gal staining to detect SA-β-gal expression. Then, additional injured distal stumps denervated for 8 weeks were employed for determining cellular distribution of SA-β-gal expression by co-labeling of SA-β-gal and SC-specific protein (S100β)., Results: SA-β-gal expression transiently increased in distal tips of proximal stumps 2 weeks after adult rat sciatic nerve transection without suture. In contrast, in the distal stumps of transected adult rat sciatic nerves, axon depletion for 2 weeks increased SA-β-gal expression, and the increased expression of SA-β-gal remained constant after prolonged denervation durations. Furthermore, combination of SA-β-gal staining with S100β immunofluorescence staining showed that SA-β-gal expression. was exclusively present in denervated SCs., Conclusion: Prolonged axon depletion increased SA-β-gal expression in adult rat SCs.

In cranial and spinal nerve ganglia, both axotomized primary sensory neurons without regeneration (axotomy-nonregenerative neurons) and spared intact primary sensory neurons adjacent to axotomized neurons (axotomy-spared neurons) have been definitely shown to participate in pain transmission in peripheral neuropathic pain states. However, whether axotomized primary sensory neurons with regeneration (axotomy-regenerative neurons) would be integral components of neural circuits underlying peripheral neuropathic pain states remains controversial. In the present study, we utilized an adult rat sciatic nerve crush model to systematically analyze pain behaviors on the glabrous plantar surface of the hindpaw sural nerve skin territories. To the best of our knowledge, our results for the first time showed that heat hyperalgesia, cold allodynia, mechanical allodynia, and mechanical hyperalgesia emerged and persisted on the glabrous sural nerve skin areas after adult rat sciatic nerve crush. Interestingly, mechanical hyperalgesia was sexually dimorphic. Moreover, with our optimized immunofluorescence staining protocol of free-floating thick skin sections for wide-field epifluorescence microscopic imaging, changes in purely regenerative reinnervation on the same skin areas by axotomized primary sensory afferents were shown to be paralleled by those pathological pain behaviors. To our surprise, Protein Gene Product 9.5-immunoreactive nerve fibers with regular and large varicosities ectopically emigrated into the upper dermis of the glabrous sural nerve skin territories after adult rat sciatic nerve crush. Our results indicated that axotomy-regenerative primary sensory neurons could be critical elements in neural circuits underlying peripheral neuropathic pain states. Besides, our results implied that peripheral neuropathic pain transmitted by axotomy-regenerative primary sensory neurons alone might be a new dimension in the clinical therapy of peripheral nerve trauma beyond regeneration.

Understanding molecular motion in terms of molecular structure is an important issue for microscopic understanding of the nature of transport properties and glass transition, and for design of structured materials to meet specific demands in various applications. Herein, a novel molecular mechanism is proposed to connect macroscopic motion in ionic liquids with molecular structure via conformational conversions of the constituent ions or of the cation-anion pairs. New equations for description of relaxation time, diffusion coefficient, molar conductivity, and viscosity of ionic liquids are established. The equation parameters, which were determined from the temperature dependent heat capacities, self-diffusion coefficients, molar conductivities, and viscosities of typical ionic liquids, were used to produce predictions for the corresponding properties of other ionic liquids and for the glass transition temperatures of representative ionic liquids. All predictions are in nice agreements with the experimental results.

A single nucleotide polymorphism of MYC rs9642880 (G>T) at the 8q24.1 locus is thought to be associated with bladder cancer risk based on the results of genome-wide association studies, but the results remain inconclusive. To assess the association between rs9642880[T] allele and bladder cancer risk, we performed this meta-analysis including 18 case-control studies and involving 23,084 cases and 97,164 controls. Electronic searches for publications were conducted to determine the association between this variant and prostate cancer in several databases. The last search update was August 4, 2014. We used odds ratios and 95%CIs to evaluate the strength of the associations. The overall results suggested that the rs9642880[T] allele was associated with bladder cancer susceptibility (T vs G, odds ratio = 1.18, 95%CI = 1.14-1.22). In subgroup analysis by ethnicity and source of controls, the risk remained significant. The present meta-analysis suggests that the MYC rs9642880[T] allele is significantly associated with bladder cancer risk.

Objective: To study the clinical features and treatment outcomes of cardiovascular system involvement in children with methylmalonic aciduria combined with hyperhomocysteinemia (MMACHC)., Methods: The clinical data of 10 children with methylmalonic aciduria combined with hyperhomocysteinemia and who had cardiovascular system involvement were retrospectively analyzed and the treatment outcomes were followed up., Results: In the 10 patients, there were 4 cases with initial presentations of cardiovascular system symptoms such as shortness of breath and dyspnea, 3 cases with urinary tract symptoms such as edema, hematuria and proteinuria, and 3 cases with nervous system symptoms such as developmental retardation and convulsions. The 10 patients had different types and severity of cardiovascular injuries. After 3 months to 8 years of follow-up, the congenital heart defects resolved naturally in 2 cases, and the patient with arrhythmia had no obvious changes. In 5 cases of hypertension, blood pressures recovered to normal in 3 cases, and 1 case was lost to follow-up. In 5 patients with pulmonary hypertension, 2 died, 2 recovered, and 1 case had mildly elevated pulmonary artery pressure. Seven patients underwent MMACHC gene testing, and 5 showed c.80A>G mutations., Conclusions: Metabolic disease should be taken into account for the children with unexplained pulmonary hypertension and hypertension with the onset of the shortness of breath and dyspnea. The severity of cardiovascular system involvement might be one of the most important factors affecting the prognosis of children with MMACHC. Cardiavascular system involvement of the patients may be related to MMACHC c.80A>G mutations.

Genome-wide studies have reported an association between the HNF1B rs4430796 (A>G) polymorphism and prostate cancer risk, but results have been inconsistent and recent meta-analyses have been inadequate. This study aimed to integrate previous results and explore the validity of this association. Electronic searches for all relevant publications through May 18, 2014, were conducted across several databases. Additional studies were identified manually, and only the most recent or complete were used in this meta-analysis. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Seven eligible case-control studies were identified, incorporating a total of 14,049 patients and 12,674 controls. Overall, we found that the rs4430796 (A>G) polymorphism had a decreased risk of prostate cancer (GG vs AA: OR = 0.661, 95%CI = 0.615-0.710, P = 0.304; AG vs AA: OR = 0.782, 95%CI = 0.739-0.828, P = 0.435; dominant model: OR = 0.743, 95%CI = 0.704-0.784, P = 0.912; recessive model: OR = 0.764, 95%CI = 0.718-0.813, P = 0.01). Furthermore, in the stratified analysis, there were significantly decreased risks among studies with population- and hospital-based controls. In the subgroup analysis by ethnicity, significantly decreased risks were also found among Caucasians, Americans, and Asians. Our results suggested that the HNF1B rs4430796 (A>G) polymorphism decreased the risk of prostate cancer. In the future, additional and larger studies on patients from across of the world might be required to validate our findings.

Closely correlating with {200} plane of cubic phase, {103} plane of hexagonal phase of Ge(2)Sb(2)Te(5) plays a crucial role in achieving fast phase change process as well as formation of modulation structures, dislocations and twins in Ge(2)Sb(2)Te(5). The behaviors of {103} plane of hexagonal phase render the phase-change memory process as a nanoscale shape memory., (© 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.)

Peripheral nerve functional recovery after injuries relies on both axon regeneration and remyelination. Both axon regeneration and remyelination require intimate interactions between regenerating neurons and their accompanying Schwann cells. Previous studies have shown that motor and sensory neurons are intrinsically different in their regeneration potentials. Moreover, denervated Schwann cells accompanying myelinated motor and sensory axons have distinct gene expression profiles for regeneration-associated growth factors. However, it is unknown whether differential motor and sensory functional recovery exists. If so, the particular one among axon regeneration and remyelination responsible for this difference remains unclear. Here, we aimed to establish an adult rat sciatic nerve crush model with the nonserrated microneedle holders and measured rat motor and sensory functions during regeneration. Furthermore, axon regeneration and remyelination was evaluated by morphometric analysis of electron microscopic images on the basis of nerve fiber classification. Our results showed that Aα fiber-mediated motor function was successfully recovered in both male and female rats. Aδ fiber-mediated sensory function was partially restored in male rats, but completely recovered in female littermates. For both male and female rats, the numbers of regenerated motor and sensory axons were quite comparable. However, remyelination was diverse among myelinated motor and sensory nerve fibers. In detail, Aβ and Aδ fibers incompletely remyelinated in male, but not female rats, whereas Aα fibers fully remyelinated in both sexes. Our result indicated that differential motor and sensory functional recovery in male but not female adult rats is associated with remyelination rather than axon regeneration after sciatic nerve crush.

Background Aims: The neuroprotective effects of olfactory ensheathing cells (OECs) after transplantation have largely been known in the injured nervous system. However, the underlying mechanisms still must be further elucidated. We explored the effects of OEC transplantation on the recovery of neurophysiologic function and the related anti-apoptosis mechanism in acute traumatic brain injury., Methods: The OECs from neonatal Sprague-Dawley rats were isolated, identified and labeled and then were immediately transplanted into the regions surrounding the injured brain site that is resulted from free-weight drop injury., Results: Nerve growth factor and it's recepor, p75 was expressed in cultured OECs. Transplanted OECs survived, migrated around the injury site and significantly improved the neurological severe scores compared with the control group (P < 0.05). OEC transplantation significantly increased the number of GAP-43-immunopositive fibers and synaptophysin-positive vesicles (P < 0.05) but significantly decreased the number of apoptotic cells (P < 0.05). On the molecular level, the expression of Bad in the OEC transplantation group was significantly downregulated (P < 0.05)., Conclusions: OEC transplantation could effectively improve neurological deficits in TBI rats; the underlying mechanism may be related with their effects on neuroprotection and regeneration induction, which is associated with the downregulation of the apoptotic molecule Bad., (Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Transplantation of neural stem cells (NSCs) into lesioned spinal cord demonstrated a beneficial effect for neural repair, the underlying mechanism, however, remains to be elusive. Here, we showed that NSCs, possessing the capacity to differentiate toward into neurons and astrocytes, exhibit a neuroprotective effect by anti-apoptosis mechanism in spinal cord hemi-transected rats despite it did not improve behavior. Intravenous NSCs injection substantially upregulated the level of BDNF mRNA but not its receptor TrkB in hemisected spinal cord, while caspase-7, a downstream apoptosis gene of caspase-3, has been largely down-regulated. TUNEL staining showed that the number of apoptosis cells in injured spinal cord decreased significantly, compared with seen in rats with no NSCs administration. The present finding therefore provided crucial evidence to explain neuroprotective effect of NSCs grafts in hemisected spinal cord, which is associated with BDNF upregulation and caspase-7 downregulation.

Amyloid precursor protein (APP) is involved in the pathogenesis of Alzheimer's disease. It is axonally transported, endocytosed and sorted to different cellular compartments where amyloid beta (Aβ) is produced. However, the mechanism of APP trafficking remains unclear. We present evidence that huntingtin associated protein 1 (HAP1) may reduce Aβ production by regulating APP trafficking to the non-amyloidogenic pathway. HAP1 and APP are highly colocalized in a number of brain regions, with similar distribution patterns in both mouse and human brains. They are associated with each other, the interacting site is the 371-599 of HAP1. APP is more retained in cis-Golgi, trans-Golgi complex, early endosome and ER-Golgi intermediate compartment in HAP1-/- neurons. HAP1 deletion significantly alters APP endocytosis and reduces the re-insertion of APP into the cytoplasmic membrane. Amyloid precursor protein-YFP(APP-YFP) vesicles in HAP1-/- neurons reveal a decreased trafficking rate and an increased number of motionless vesicles. Knock-down of HAP1 protein in cultured cortical neurons of Alzheimer's disease mouse model increases Aβ levels. Our data suggest that HAP1 regulates APP subcellular trafficking to the non-amyloidogenic pathway and may negatively regulate Aβ production in neurons., (© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.)

Objective: To observe the effect of adrenomedullin (ADM) on the pulmonary vascular collagen metabolism in hypoxic rats in order to study the effect of ADM on chronic hypoxic pulmonary vascular structural remodeling and its possible mechanism., Methods: Nineteen male Wistar rats were randomly divided into three groups: normal control (n=6), hypoxia (n=7) and ADM-treated hypoxia (n=6). ADM was subcutaneously administered into rats of the ADM-treated hypoxia group by mini-osmotic pump (300 ng/h) for two weeks. After two weeks of hypoxic challenge, mean pulmonary arterial pressure (mPAP) was evaluated using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass[RV/ (LV+S)] was measured. The changes of pulmonary vascular microstructure were observed. Meanwhile, the expression levels of collagen I, collagen III and transforming growth factor (TGF)-β in pulmonary arteries were detected by immunohistochemical assay., Results: mPAP and RV/(LV+S) increased significantly in the hypoxia group compared with normal controls (P<0.01). The muscularization of small pulmonary vessels and the relative medial thickness of pulmonary arteries increased obviously in the hypoxia group compared with those in the normal control group (P<0.01). Meanwhile, the expression levels of collagen I, collagen III and TGF-β of pulmonary arteries in the hypoxia group increased markedly compared with those in the normal control group. However, mPAP and RV/(LV+S) were significantly reduced in the ADM-treated hypoxia group compared with those in the hypoxia group (P<0.01). ADM ameliorated pulmonary vascular structural remodeling of hypoxic rats, with a decrease in the expression of collagen I, collagen III and TGF-β of pulmonary arteries., Conclusions: ADM might play a regulatory role in the development of hypoxic pulmonary hypertension and hypoxic pulmonary vascular remodeling, through inhibiting the expression of TGF-β and alleviating the collagen accumulation of pulmonary arteries.

Objective: Tachycardia induced cardiomyopathy (TIC), secondary to various tachyarrhythmias, is a reversible condition which can lead to cardiac enlargement and heart failure. The impairment of both structure and function of heart can be reverted completely or partially if tachyarrhythmias are ceased without delay. This study aimed to explore the clinical characteristics, therapeutic regimen and outcome of TIC in children., Methods: Clinical data of 12 children with TIC, who came from Peking University First Hospital from Feb. 2003 to Jun. 2009, were retrospectively analyzed and followed up. The echocardiogram data on admission were compared with those from 12 homochronous cases with idiopathic dilated cardiomyopathy matched with 12 TIC cases in age and gender., Results: Atrial tachycardia is the commonest arrhythmia in 12 TIC cases (75%). Four cases underwent catheterization for radiofrequency ablation and all succeeded. The cardiac rhythm of 6 out of 8 cases treated with drugs became sinus rhythm after 3 days to 2 weeks antiarrhythmic drugs treatment. The remaining 2 cases still retained atrial rhythm, but the ventricular heart rates declined to normal. The left ventricular end-diastolic dimensions of the 12 cases were decreased compared with those of pretherapy [(37.5 ± 5.3) mm vs. (43.0 ± 5.7) mm, P < 0.01], and the left ventricular ejection fractions were increased [(60.5% ± 5.6%) vs. (33.7% ± 10.3%), P < 0.01], after (3.4 ± 2.3) months. In our (4.3 ± 2.4) year-follow-up, all cases were fine, except in one case the tachyarrhythmia relapsed because of discontinuation of the drug treatment by her parents. The left ventricular end-diastolic dimensions in 12 TIC cases were smaller than those of the 12 age- and gender-matched idiopathic dilated cardiomyopathy [(43.0 ± 5.7) mm vs. (54.8 ± 7.5) mm, t = 7.9, P < 0.01], and the ejection fractions were higher [(33.7% ± 10.3%) vs. (21.8% ± 7.5%), t = 3.7, P < 0.01]., Conclusion: The diagnosis of TIC should be considered for the children with tachycardia, cardiac enlargement and cardiac insufficiency. The degree of cardiac enlargement and cardiac insufficiency might be of value for the differential diagnosis between TIC and idiopathic dilated cardiomyopathy. The rhythm control and ventricular rates control could all result in a favorite therapeutic efficacy.

Objective: To improve the diagnosis and management of Duchenne/Becker muscular dystrophy(DMD/BMD)., Methods: Clinical features of 90 cases of DMD/BMD were collected. Genomic DNA was extracted using standard procedures from the peripheral blood leukocytes, and multiplex ligation-dependent probe amplification (MLPA) was applied to detect DMD gene to identify genetic mutation. For those patients whose deletion/duplication mutation was not identified, FKRP gene mutation analysis was performed using PCR-DNA direct sequence. All the cases were followed up., Results: Among the 90 cases of clinically diagnosed DMD/BMD, exons deletion of DMD was detected in 58 cases (64.44%), and exons duplication in 9 (10.00%). Among the 34 mothers with an affected boy but without previous genetic conformation, 17 were confirmed to be carriers with gene deletion/duplication. None of the 23 cases, without detected DMD gene deletion/duplication, carried FKRP gene mutation. Fourteen children were given short-term intermittent prednisone therapy (0.75 mg/kg daily during the first 10 days of each month). The course was not long enough and the sample size was too small to conclude any benefits or side effects. Prenatal diagnosis was provided for one mother in her next pregnancy detecting a female carrier fetus., Conclusion: DMD gene deletions mainly occurs between exons 45 and 54, while duplications mostly at 5'-terminus. Identification of the characteristics and types of gene mutation may facilitate the recognition and prognosis prediction of DMD/BMD. MLPA is a non-complex and quick diagnostic tool for DMD/BMD and its carriers, and also helpful in genetic counseling.

Objective: To investigate the pathohistological characteristics of the prostate tissues in patients who receive a second TURP and to evaluate their clinical significance., Methods: We collected surgical specimens from 50 cases of TURP (the control group) and another 50 cases of re-TURP (the re-TURP group), detected the expressions of CD34, vascular endothelial growth factor (VEGF) and androgen receptor (AR) in the prostate tissues by immunohistochemistry (S-P), and determined microvessel density (MVD) and the expressions of VEGF and AR. We performed statistical analyses on the results obtained from the specimens of the control group as well as from those of the first and second operations of the re-TURP group., Results: VEGF and AR expressed in all the specimens. The expressions of VEGF and AR and MVD were significantly higher in the re-TURP group than in the controls (P < 0.05), but showed no significant differences between the first and second operations in the re-TURP group (P > 0.05). Positive correlations were found between the expressions of AR and VEGF, VEGF and MVD, and AR and MVD (r = 0.650, 0.705 and 0.525, P < 0.05)., Conclusion: Increased AR, VEGF and MVD in the prostatic tissues may be one of the important causes of recurrence of BPH after TURP, and could be considered as the risk factors for postoperative recurrence and targeted indicators for preventive measures.

Objectives: To explore the clinical characteristics of cardiac syncope (CS) in children, and understand their significance in predicting the cardiac syncope., Methods: Twenty-three patients were referred to our department for evaluation of syncope. The diagnosis of the above cases was cardiac syncope. Each patient was interviewed using a standard questionnaire. The clinical histories and standard baseline electrocardiogram were analyzed to identify the variables contributing to the diagnosis of CS in children., Results: A cardiac cause was identified in 23 syncopal patients presenting to the Department of Pediatrics, Peking University First Hospital: sick sinus syndrome in 7, congenital long QT syndrome in 4, third degree atrioventricular block in 2, supraventricular tachycardia in 2, ventricular tachycardia in 1, atrial fibrillation in 1, pacemaker dysfunction in 1, idiopathic pulmonary hypertension in 3, hypertrophic cardiomyopathy in 1, and dilated cardiomyopathy in 1. The average age of CS patients was 9 years. In totally 23 patients, exertion related syncope spells were found in 14 cases (60.9%), syncope spells at various position 7/23 (30.4%), absence of prodromes in 12/23 (52.2%), syncope spells with incontinence in 4/23 (17.4%), history of heart disease in 4/23 (17.4%). Abnormal standard baseline electrocardiogram was found in 21 cases (91.7%)., Conclusions: The children with cardiac syncope have overt clinical features, especially abnormal findings in electrocardiogram and exertion related syncope spells are the most common clinical features.

Objective: To study the clinical characteristics, therapeutic regimen and outcome of severe Mycoplasma pneumonia (MP) in children., Methods: Clinical data of 79 children with MP, including 69 mild and 10 severe cases, were retrospectively analyzed. The 10 children with severe MP were followed-up., Results: In severe MP cases, the fever duration prior to hospitalization and the total fever duration were more prolonged, peripheral blood leucocytes counts, C-reactive protein and erythrocyte sedimentation rate increased, and serum IgM and IgE levels increased as compared to mild MP cases. Of the 10 cases of severe MP, 4 manifested as pulmonary consolidation, 4 as pulmonary consolidation complicated by moderate to large pleural effusion and 2 as progressively worsening pulmonary radiographic findings. Nine severe MP cases were administered with glucocorticoid as well as antibiotics, and the therapeutic effect was satisfactory. In the convalescence stage, bronchofiberoscope lavages were used in 5 severe cases because of persistent pulmonary consolidation., Conclusions: Severe MP was characterized by rapid progression, pulmonary consolidation, moderate to severe pleural effusion, obviously increased inflammatory indexes, and poor therapeutic reaction to simple macrolide antibiotics. Besides antibiotics, glucocorticoid should be used for severe MP cases as soon as possible. For severe cases with persistent pulmonary consolidation, bronchofiberoscope lavages are recommended.

It is well known that some growth factors can not only rescue neurons from death, but also improve motor functions following spinal cord injury. However, their cellular distribution in situ and temporal expressions following spinal cord injury have not been determined, especially in primates. This study investigated the temporal changes in the expression of two growth factors--epidermal growth factor (EGF) and transforming growth factor-beta 1 (TGF-beta1) in the injured motoneurons of the spinal cord and the associated precentral gyrus in adult Rhesus monkeys subjected to spinal cord hemisection. Animals were allowed to survive 7, 14, 30 and 90 days post operation (dpo). Functional recovery of the hindlimbs was assessed using Tarlov scale. The immunohistological expressions of EGF and TGF-beta1 in the ventral horn motoneurons decreased sharply at 7 dpo in the cord segments caudal to the lesion site, which was followed by an increase and a peak between 14 and 30 dpo for EGF and at 90 dpo for TGF-beta1. Changes in the expression of EGF in the precentral gyrus were similar to that in the spinal cord. No TGF-beta1 immunoreactive neurons were detected in the precentral gyrus. In the spinal segments rostral to the lesion, the expressions of EGF and TGF-beta1 peaked at 30 dpo. The mRNA of EGF was detected in both spinal motoneurons and the precentral gyrus, while that of TGF-beta1, only in the spinal motoneuons, suggesting that the spinal motoneurons themselves could synthesize both the growth factors. Partial locomotor recovery in hindlimbs was seen, especially after 14 dpo. It was concluded that a possible association existed between the modulation of EGF and TGF-beta1 and the recovery of locomotor function, and their roles differed somewhat in the neuroplasticity observed after spinal cord injury in primates.

Neurotrophin-3 plays an important role in survival and differentiation of sensory and sympathetic neurons, sprouting of neurites, synaptic reorganization, and axonal growth. The present study evaluated changes in expression of NT-3 in the spinal cord and L6 dorsal root ganglion (DRG), after ganglionectomy of adjacent dorsal roots in cats. NT-3 immunoreactivity increased at 3 days post-operation (dpo), but decreased at 10 dpo in spinal lamina II after ganglionectomy of L1-L5 and L7-S2 (leaving L6 DRG intact). Conversely, NT-3 immunoreactivity decreased on 3 dpo, but increased on 10 dpo in the nucleus dorsalis. Very little NT-3 mRNA signal was detected in the spinal cord, despite the changes in NT-3 expression. The above changes may be related to changes in NT-3 expression in the DRG. Ganglionectomy of L1-L5 and L7-S2 resulted in increase in NT-3 immunoreactivity and mRNA in small and medium-sized neurons, but decreased expression in large neurons of L6 DRG at 3 dpo. It is possible that increased NT-3 in spinal lamina II is derived from anterograde transport from small- and medium-sized neurons of L6 DRG, whereas decreased NT-3 immunoreactivity in the nucleus dorsalis is due to decreased transport of NT-3 from large neurons in the DRG at this time. This notion is supported by observations on NT-3 distribution in the dorsal root of L6 after ligation of the nerve root. The above results indicate that DRG may be a source of neurotrophic factors such as NT-3 to the spinal cord, and may contribute to plasticity in the spinal cord after injury.

This study evaluated the effect of electro-acupuncture (EA) on the NGF, BDNF and NT-3 expression in spared L6 dorsal root ganglion (DRG) in cats subjected to bilateral removal of L1-L5 and L7-S2 DRG, using immunostaining, in situ hybridization and RT-PCR. The positive products of NGF, NT-3 protein and mRNA in the small and large neurons of spared L6 DRG in EA side increased greatly more than that of control side, while the increased BDNF was only noted in small and medium-sized neurons. RT-PCR demonstrated that the mRNA level for three factors was not influenced by EA in intact DRG, when a significant increase was seen in the spared L6 DRG of EA side. As it has been well known that DRG neurons project to the spinal cord wherein morphological plasticity has been present after DRG removal, the present results might have some bearing to the observed phenomenon.

Objective: The mechanism of high pulmonary blood flow-induced pulmonary hypertension remains unclear. The aim of this study was to explore the effect of proadrenomedullin N-terminal 20-peptide (PAMP) on pulmonary hypertension, through examining the alterations of pulmonary PAMP expression and plasma PAMP concentration in rats with pulmonary hypertension induced by high pulmonary blood flow., Methods: Sixteen male Sprague-Dawley rats were randomly divided into control (n=8) and shunt groups (n=8). Aortocaval shunting was produced in the shunt group. After 11 weeks of shunting, systolic pulmonary artery pressure (sPAP), diastolic pulmonary artery pressure (dPAP) and mean pulmonary artery pressure (mPAP) were evaluated by using a right cardiac catheterization procedure. The ultrastructural changes in intra-acinar pulmonary arteries were observed. The concentration of plasma PAMP was measured by radioimmunoassay. The expression of PAMP in pulmonary arteries was detected by immunohistochemical assay., Results: sPAP, dPAP and mPAP were significantly increased in shunt rats compared with controls (P < 0.01). Ultrastructural changes, such as hyperplasia and swelling of endothelial cells, irregularity of internal elastic laminar, and hypertrophy and increased number of synthetic phenotype of smooth muscle cells, were found in intra-acinar pulmonary muscularized arteries in the shunt group. Plasma PAMP concentration (616 +/- 195 pg /mL vs 427 +/- 90 pg /mL) and PAMP expression in endothelial cells (0.62 +/- 0.09 vs 0.38 +/- 0.12) and in smooth muscle cells (0.24 +/- 0.07 vs 0.14 +/- 0.05) of pulmonary arteries increased significantly in the shut group compared with controls., Conclusions: The up-regulation of pulmonary and plasm PAMP expression might be involved in the development of high pulmonary blood flow-induced pulmonary hypertension.

Adrenomedullin (ADM) is a novel cardiovascular-active peptide involved in vasodilation, reducing blood pressure and inhibiting vascular smooth muscle cell migration and proliferation. Previous research showed that ADM might be involved in the development of pulmonary hypertension. In this study, we investigated the effect of ADM subcutaneously administered by mini-osmotic pump (300 ng/h) on pulmonary hemodynamics and pulmonary vascular structure in hypoxic rats, as well as the influence of ADM on the proadrenomedullin N-terminal 20-peptide (PAMP) protein and mRNA expressions and its plasma concentrations. The results showed that ADM obviously decreased mean pulmonary artery pressure and the ratio of right ventricular mass to left ventricular plus septal mass in hypoxic rats. Chronic infusion of ADM lessened the muscularization of small pulmonary vessels, attenuated relative medial thickness and relative medial area of pulmonary arteries, and alleviated the ultrastructural changes in pulmonary arteries of hypoxic rats. ADM inhibited the proliferation of pulmonary artery smooth muscle cells, represented by a decrease in the expression of proliferative cell nuclear antigen (PCNA) in the pulmonary artery. Meanwhile, plasma PAMP concentration and the expression of PAMP protein and mRNA by pulmonary arteries in rats of hypoxia with ADM group were markedly decreased compared with those in hypoxic group. The results suggest that ADM ameliorated the development of hypoxic pulmonary vascular structural remodeling. Intramolecular regulation of ADM may play an important role in the regulation of hypoxic pulmonary hypertension by ADM.

Background: Hypertension is a common disease of the cardiovascular system. So far, the pathogenesis of primary hypertension remains unclear. The elaboration of its pathogenesis is an important topic in the field which calls for urgent resolution. The aim of this study was to probe into the metabolic imbalance of homocysteine (Hcy) and hydrogen sulfide (H(2)S) in children with essential hypertension, and its significance in the pathogenesis of essential hypertension., Methods: Twenty-five children with essential hypertension and 30 healthy children with normal blood pressure were enrolled in the study. The medical history was investigated and a physical examination was conducted on the subjects. Plasma Hcy content was examined by fluorescence polarization immunoassay (FPIA). The plasma H(2)S level was detected by a modified method with a sulfide electrode. Data were presented as mean +/- standard deviation. The t test was applied to the mean values of both groups. Pearson linear correlation analysis was applied to the plasma Hcy and H(2)S as well as to the systolic pressure against the plasma H(2)S/Hcy ratio., Results: Plasma Hcy, an intermittent metabolite of the endogenous methionine pathway, was markedly increased but plasma H(2)S, a final product of this pathway was significantly decreased in hypertensive cases when compared with normal subjects ((Hcy: (12.68 +/- 9.69) micromol/L vs (6.62 +/- 4.79) micromol/L (t = 2.996, P < 0.01); H(2)S: (51.93 +/- 6.01) micromol/L vs (65.70 +/- 5.50) micromol/L) (t = -8.670, P < 0.01)). The ratio of plasma H(2)S/Hcy in children with hypertension was 5.83 +/- 2.91, while that of the control group was 11.60 +/- 3.30, and the difference is significant with a t = -6.610 and P < 0.01. A negative correlation existed between plasma Hcy and H(2)S concentrations, r = -0.379, P < 0.05. And a negative correlation was found between systolic blood pressure and the plasma H(2)S/Hcy ratio, r = -0.687, P < 0.05., Conclusion: There was a metabolic imbalance of homocysteine and hydrogen sulfide in essential hypertensive children.

Objective: To observe the changes in the amount of epidermal growth factor (EGF) immunopositive neurons in ventral horn and contralateral cortex motor area of rhesus following hemisection spinal cord injury (hSCI)., Methods: Eighteen adult healthy rhesus were randomly divided into six groups: Sham-operation group; Day 7, Day 14, Month 1. Month 2 and Month 3 hemisection spinal cord injury groups. In the hSCI groups, the monkeys were subjected to left hemisection of T11 spinal cord, and then were put to death at the corresponding time after operation. The rostral part 5 mm proximal to the lesioned point of spinal cord and the caudal part 5 mm distal to the lesioned point were taken from each monkey. The contralateral cortex motor area was taken out, too. Frozen sections were incubated in specific polyclonal anti-EGF antibody; the immunohistochemical SP method was adopted in the study., Results: In 3 months after hSCI, the number of EGF immunopositive neurons in the ventral horn of spinal cord near the lesion and in the contralateral cortex motor area of brain decreased as compared with those of the sham-operation group (P<0.05). The number of positive neurons decreased first, then came back, and later after hSCI, decreased again (P<0.05). Besides this, the number of positive neurons varied in different parts at the same time point., Conclusion: The EGF immunopositive neurons decreased apparently in the ventral horn of spinal cord near the lesion and in the contralateral cortex motor area in 3 months after hSCI. Hemisection spinal cord injury affected the expression of EGF for motor neurons in ventral horn on the lesioned side as well as on the intact side. Early after hSCI the number of positive neurons decreased sharply and then came back spontaneously in the ventral horn of spinal cord near the lesion and in the contralateral cortex of brain.

Aim: Pulmonary hypertension is a common complication of congenital heart disease with a left-to right shunt. The mechanism of pulmonary hypertension induced by high pulmonary blood flow is still not fully understood. Recent studies showed that hydrogen sulfide (H2S) could relax vascular smooth muscle cells. But the change of the system of H2S in pulmonary hypertension induced by high pulmonary blood flow was not reported. We studied the influence on expression of CSE mRNA and production of hydrogen sulfide in rat lung tissues by L-Arginine, in order to demonstrate a regulating role of nitric oxide (NO) in the regulation of cystathionine-gamma-lyase/hydrogen sulfide system (CSE/H2S)., Methods: Thirty male SD rats were randomly divided into shunting group, shunting with L-Arginine group, and control group. Abdominal aorta and inferior vena cava shunting was produced in rats of the later group. Pulmonary artery mean pressure (mPAP) and the hypertrophy of right ventricle of each rat were analyzed. The expression of lung tissue CSE mRNA was measured using quantitative reverse transcription-polymerase chain reaction and in situ hybridization. The activity of CSE in lung tissue was measured according to chemical analysis., Results: mPAP was significantly increased in shunted rats compared with normal control (P < 0.01), the expression of lung tissue CSE mRNA and the activity of CSE in lung tissue were decreased in shunt group (P < 0.01). However, L-arginine significantly attenuated pulmonary artery pressure, but augmented the expression of lung tissue CSE mRNA as well as the activity of CSE in lung tissue., Conclusion: L-Arginine reverses the down-regulation of CSE/H2S system in high pulmonary blood flow-induced pulmonary hypertension.

Objective: To explore the effect of adrenomedullin(1-50) (ADM(1-50)) on hypoxic pulmonary hypertension and pulmonary vascular structural remodeling and the plasma concentration of nitric oxide (NO) and hydrogen sulfide (H(2)S) in rats., Methods: Twenty male Wistar rats were randomly divided into control group (n=7), hypoxic group (n=6) and hypoxic with ADM(1-50) group (n=7). ADM(1-50) was subcutaneously administered into rats of hypoxic with ADM(1-50) group by mini-osmotic pump (300 ng/h). After two weeks' hypoxic challenge, mean pulmonary arterial pressure (mPAP) was evaluated by using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass [RV/(LV+S)] was detected. Pulmonary vascular microstructure was measured and the ultrastructural changes in intra-acinar pulmonary arteries were observed. Meanwhile, plasma concentrations of NO and H(2)S were measured., Results: mPAP was significantly increased in hypoxic rats than that in controls [(24.9+/-6.8) mmHg vs (14.3+/-2.4) mmHg, P<0.01,1 mmHg=0.133 kPa]; RV/(LV+S) was also significantly increased in hypoxic rats than that in controls [(0.318+/-0.054) vs (0.182+/-0.007), P<0.01]. Microstructure and ultrastructure of pulmonary arteries changed obviously in hypoxic rats with the development of hypoxic pulmonary vascular structural remodeling. Meanwhile, plasma NO and H(2)S concentrations in hypoxic rats were markedly decreased compared with controls. However, mPAP was significantly decreased in hypoxic rats treated with ADM(1-50) than that in hypoxic rats [(14.9+/-3.0) mmHg vs (24.9+/-6.8) mmHg, P<0.01]; RV/(LV+S) was also significantly decreased than that in hypoxic rats [(0.185+/-0.011) vs (0.318+/-0.054), P<0.01]. ADM(1-50) ameliorated pulmonary vascular structural remodeling of hypoxic rats in association with an increase in plasma NO and H(2)S concentrations., Conclusion: ADM(1-50) plays an important role in regulation of the development of hypoxic pulmonary hypertension and hypoxic pulmonary vascular structural remodeling, through promoting NO and H(2)S production in hypoxic rats.

This study investigated the effect of L-arginine (L-Arg) on the apoptosis of pulmonary artery smooth muscle cells (PASMC) in rats with hypoxic pulmonary vascular structural remodeling, and its mechanisms. Seventeen Wistar rats were randomly divided into a control group (n=5), a hypoxia group (n=7), and a hypoxia+L-Arg group (n=5). The morphologic changes of lung tissues were observed under optical microscope. Using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay, the apoptosis of PASMC was examined. Fas expression in PASMC was examined using immunohistochemistry. The results showed that the percentage of muscularized artery in small pulmonary vessels, and the relative medial thickness and relative medial area of the small and median pulmonary muscularized arteries in the hypoxic group were all significantly increased. Pulmonary vascular structural remodeling developed after hypoxia. Apoptotic smooth muscle cells of the small and median pulmonary arteries in the hypoxia group were significantly less than those in the control group. After 14 d of hypoxia, Fas expression by smooth muscle cells of median and small pulmonary arteries was significantly inhibited. L-Arg significantly inhibited hypoxic pulmonary vascular structural remodeling in association with an augmentation of apoptosis of smooth muscle cells as well as Fas expression in PASMC. These results showed that L-Arg could play an important role in attenuating hypoxic pulmonary vascular structural remodeling by upregulating Fas expression in PASMC, thus promoting the apoptosis of PASMC.

Matrix metalloproteinases (MMPs) play crucial roles in extravillous trophoblast invasion. In the present study, we examined the possible role of Smad4 and Smad2 in transforming growth factor (TGF)-beta1-induced MMP-2 expression, using the well-established invasive extravillous trophoblast cell line HTR-8/SVneo. Recombinant sense Smad4 or Smad2 retroviral vectors were constructed by inserting full-length Smad4 or Smad2 cDNA into pLXSN retroviral vector. Stable PT67 packaging cell clones were isolated and viral supernatants were used to infect HTR-8/SVneo cells. Effects of retroviral expression of Smad4 and Smad2 on TGF-beta1-regulated MMP-2 expression were assessed by semi-quantitative reverse transcription-polymerase chain reaction and gelatin zymography. The results showed that over-expression of Smad4 augmented MMP-2 mRNA abundance and the secretion of pro-MMP-2, and mimicked the inductive effect of TGF-beta1 on the production of MMP-2. However, retrovirus-mediated sense Smad2 gene transfer had no effect. These findings suggest that Smad4, but not Smad2, mediates TGF-beta1-induced MMP-2 expression in invasive extravillous trophoblasts.