[Analysis on the management of type 2 inflammatory asthma from the guideline of Global Strategy for Asthma Management and Prevention].

Bronchial asthma is a common chronic respiratory disease, which is involved in a variety of cells and cellular components. In 2019, the guidelines for the diagnosis and treatment of asthma issued by the Global Initiative for Asthma (GINA) Committee put forward the concept of type 2 inflammatory asthma for the first time. The updated evolution of GINA guidelines has promoted the development of biological agents and disease treatment, providing effective prevention and treatment for patients with severe asthma and improving disease outcome. This paper expounds the disease mechanism and management suggestions of type 2 inflammatory asthma in GINA guidelines, and analyzes the relevant clinical studies on targeted treatment of type 2 inflammatory asthma in recent years, in order to provide reference for in-depth understanding of level 3 prevention and management of patients with type 2 inflammatory asthma.

[Efficacy comparison and safety analysis of subcutaneous specific immunotherapy with standardized house dust mite allergen in patients with single and multiple allergic rhinitis].

Objective: To investigate the efficacy and safety of house dust mite (HDM) allergen subcutaneous specific immunotherapy (SCIT) in patients with allergic rhinitis (AR) with single dust mite allergy and multiple allergen allergy. Methods: A retrospective study was conducted. A total of 372 patients with allergic rhinitis induced by house dust mite were diagnosed in the allergy clinic of General Hospital of North Theater Command from January 2013 to January 2018.They were treated with house dust mite allergen preparation for standardized SCIT for 3 years or more, and had complete follow-up data. The age ranged from 5 to 55 years, the median age was 13 years, and the average age was (19.4±14.7) years; 216 males and 156 females. According to their age, they were divided into the older group (age >14 years) and younger group (age ≤ 14 years). According to the number of allergens, they were divided into single group (only HDM group allergic to house dust mites) and multi recombination (including 2 or more allergens including house dust mites). The multi recombination was further divided into HDM+1 group, HDM+2 group, HDM+3 group, HDM+4 and above group. Before treatment (T0), 1 year (T1) and 3 years (T2) after SCIT treatment, the patients in each group established files, analyzed and compared the average total nasal symptoms score (TNSS), total non nasal symptoms score (TNNSS), visual analogue scale (VAS), total medicine score (TMS) and rhinoconjunctivitis quality of life questionnaire (RQLQ), and evaluated the clinical efficacy of the treatment and the comparison of various scores in the efficacy of SCIT with different allergens and ages. Record the occurrence of local and systemic adverse reactions of all patients during treatment, and evaluate the safety of SCIT. All scores are measurement data that do not conform to normal distribution. Mann-Whitney U and Kruskai-Wallis test of independent samples are used for inter group comparison, and Bonferroni correction is used for further pairwise comparison; Chi square test and continuity correction method were used for the comparison between count data groups such as the incidence of adverse reactions and the effective rate of TNSS, and a-division method was used for further pairwise comparison. Results: After SCIT treatment, the scores of TNSS, TNNSS, TMS, VAS and RQLQ in T1 and T2 were significantly lower than those in T0, and the scores in T2 were significantly lower than those in T1 (Z=-11.168, -4.786, -6.639, -13.012, -10.652 in T0 vs T1; Z=-13.527, -8.746, -13.397, -14.477, -11.833 in T0 vs T2; Z=-4.721, -4.607, -10.020, -7.180, -5.721 in T1 vs T2; P<0.05). In T1 and T2, compared with the older group, the scores of TNSS, TNNSS, TMS, VAS and RQLQ in younger group were lower, and the differences of various indexes were statistically significant(the median scores of T1: Myounger=3.0, 1.0, 2.0, 4.0, 2.6, Molder=5.0, 2.0, 3.0, 5.0, 3.2; the median scores of T2: Myounger=3.0, 1.0, 0, 2.0, 1.3, Molder=4.0, 1.0, 1.5, 3.0, 2.3; ZT1=-4.525, -5.830, -4.061, -3.608, -2.785; ZT2=-3.847, -4.055, -2.820, -2.998, -3.418; P<0.05). In T1 and T2, the scores of TNSS, VAS and RQLQ in a single group after SCIT treatment were lower than those in multiple recombination(the median scores of T1:Msingle=4.0, 4.0, 2.6, Mmultiple=5.0, 5.0, 3.2; the median scores of T2: Msingle=3.0, 2.0, 1.4, Mmultiple=4.0, 3.0, 2.1), and the difference was statistically significant (ZT1=-3.002, -2.092, -1.977; ZT2=-3.354, -2.469, -2.116; P<0.05). There was no significant difference in TMS (the median score during T1 period: Msingle=2.0, Mmultiple=3.0, ZT1=-1.130; the median score during T2 period: Msingle=1.0, Mmultiple=1.0, ZT2=-1.544; P>0.05). Further comparison within the group showed that there was no significant difference in the improvement rate of TNSS during T2 period among HDM group, HDM+1 group, HDM+2 group and HDM+3 group (HDM vs HDM+1 group χ2=0.277, HDM vs HDM+2 group χ2=0.78, HDM vs HDM+3 group χ2=0.075, HDM+1 vs HDM+2 group χ2=0.057, HDM+1 vs HDM+3 group χ2=0.019, HDM+2 vs HDM+3 group χ2=0.003; P>0.005), the improvement rates were 92.5%, 90.3%, 89.1% and 89.5%. Respectively in HDM group,HDM+1 group, HDM+2 group, HDM+3 group, compared with HDM+4 and above group, the difference was statistically significant (χ2=26.144, 13.254, 15.144, 8.808; P<0.005). The improvement rate of TNSS in HDM+4 and above group was 60.9%. 122 patients had local adverse reactions during the treatment of SCIT, accounting for 32.8%. The local adverse reactions were 759 injections (15 336 injections in total), accounting for 4.95%. Most of them were swelling, dizziness, induration and pruritus at the injection site, which could be relieved by oral antihistamines or within 2 hours. There were 2 cases of local urticaria, once for each case. The symptoms were relieved within 1 week after oral antihistamine. No serious systemic adverse reactions occurred. Conclusion: Standardized SCIT may be a safe and effective treatment for AR patients, and the type of allergen may be one of the important factors affecting the efficacy of SCIT. The efficacy of SCIT was significant in AR patients with three or less allergens other than house dust mite.

[Analysis of the way of thinking on pharmacology in Lu Zhiyi's Bencao Chengya Banji].

More than 410 kinds of prescriptions of medicines were presented, some of which were collected in Shennong Bencao Jing(, Shennong's Classic of Materia Medica) and other herbal works, are included in Lu Zhiyi's Bencao Chengya Banji(). He introduced the indications of these medicines by focusing on the name of the herbs, or the species of them, and the features and growth morphology of the herbs. He abstracted the efficacy of drugs on the human body. Therefore, he noted the indications of all the medicines list in the book.

Isometric Finger Pose Recognition with Sparse Channel SpatioTemporal EMG Imaging.

High fidelity myoelectric control of prostheses and orthoses isparamount to restoring lost function to amputees and neuro-muscular disease sufferers. In this study we prove that patio-temporal imaging can be used to allow convolutional neural networks to classify sparse channel EMG samples from a consumer-grade device with over 94 % accuracy. 10,572 images are generated from 960 samples of simple and complex isometric finger poses recorded from 4 fully intact subjects. Real-time classification of 12 poses is achieved with a 250ms continuous overlapping window.

Iron intake, serum iron indices and risk of colorectal adenomas: a meta-analysis of observational studies.

To provide a quantitative assessment of the association between iron intake, serum iron indices and the risk of colorectal adenoma (CRA), we summarised the evidence from observational studies. Relevant studies were identified in MEDLINE and EMBASE until 31 March 2015. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. A total of 10 articles, involving 3318 subjects with CRA, were used in this meta-analysis. The SRR of CRA was 0.83 (95% CI: 0.71-0.98; Pheterogeneity  = 0.694, I2  = 0) for the highest versus the lowest level of dietary iron intake. The SRR was 0.93 (95% CI: 0.62-1.42) for total (dietary and supplemental) iron intake, 1.23 (95% CI: 1.03-1.48) for haem iron intake and 0.73 (95% CI: 0.54-0.97) for supplemental iron intake. Serum iron indices were not associated with CRA risk (serum ferritin: SRR = 1.16, 95% CI: 0.81-1.66; serum iron: SRR = 1.02, 95% CI: 0.75-1.38; serum transferrin saturation: SRR = 1.01; 95% CI: 0.82-1.50). Increased intake of haem iron is associated with significantly increased risk of CRA, whereas intake of non-haem or supplemental iron is inversely associated with risk of CRA. Limited data indicate null associations between serum iron indices and CRA risk.

Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea.

Recent studies have reported the role of Wnt/ß-catenin signaling in hair cell (HC) development, regeneration, and differentiation in the mouse cochlea; however, the role of Wnt/ß-catenin signaling in HC protection remains unknown. In this study, we took advantage of transgenic mice to specifically knockout or overactivate the canonical Wnt signaling mediator ß-catenin in HCs, which allowed us to investigate the role of Wnt/ß-catenin signaling in protecting HCs against neomycin-induced damage. We first showed that loss of ß-catenin in HCs made them more vulnerable to neomycin-induced injury, while constitutive activation of ß-catenin in HCs reduced HC loss both in vivo and in vitro. We then showed that loss of ß-catenin in HCs increased caspase-mediated apoptosis induced by neomycin injury, while ß-catenin overexpression inhibited caspase-mediated apoptosis. Finally, we demonstrated that loss of ß-catenin in HCs led to increased expression of forkhead box O3 transcription factor (Foxo3) and Bim along with decreased expression of antioxidant enzymes; thus, there were increased levels of reactive oxygen species (ROS) after neomycin treatment that might be responsible for the increased aminoglycoside sensitivity of HCs. In contrast, ß-catenin overexpression reduced Foxo3 and Bim expression and ROS levels, suggesting that ß-catenin is protective against neomycin-induced HC loss. Our findings demonstrate that Wnt/ß-catenin signaling has an important role in protecting HCs against neomycin-induced HC loss and thus might be a new therapeutic target for the prevention of HC death.

Reduced mtDNA copy number increases the sensitivity of tumor cells to chemotherapeutic drugs.

Many cancer drugs are toxic to cells by activating apoptotic pathways. Previous studies have shown that mitochondria have key roles in apoptosis in mammalian cells, but the role of mitochondrial DNA (mtDNA) copy number variation in the pathogenesis of tumor cell apoptosis remains largely unknown. We used the HEp-2, HNE2, and A549 tumor cell lines to explore the relationship between mtDNA copy number variation and cell apoptosis. We first induced apoptosis in three tumor cell lines and one normal adult human skin fibroblast cell line (HSF) with cisplatin (DDP) or doxorubicin (DOX) treatment and found that the mtDNA copy number significantly increased in apoptotic tumor cells, but not in HSF cells. We then downregulated the mtDNA copy number by transfection with shRNA-TFAM plasmids or treatment with ethidium bromide and found that the sensitivity of tumor cells to DDP or DOX was significantly increased. Furthermore, we observed that levels of reactive oxygen species (ROS) increased significantly in tumor cells with lower mtDNA copy numbers, and this might be related to a low level of antioxidant gene expression. Finally, we rescued the increase of ROS in tumor cells with lipoic acid or N-acetyl-L-cysteine and found that the apoptosis rate decreased. Our studies suggest that the increase of mtDNA copy number is a self-protective mechanism of tumor cells to prevent apoptosis and that reduced mtDNA copy number increases ROS levels in tumor cells, increases the tumor cells' sensitivity to chemotherapeutic drugs, and increases the rate of apoptosis. This research provides evidence that mtDNA copy number variation might be a promising new therapeutic target for the clinical treatment of tumors.

Bmi1 regulates auditory hair cell survival by maintaining redox balance.

Reactive oxygen species (ROS) accumulation are involved in noise- and ototoxic drug-induced hair cell loss, which is the major cause of hearing loss. Bmi1 is a member of the Polycomb protein family and has been reported to regulate mitochondrial function and ROS level in thymocytes and neurons. In this study, we reported the expression of Bmi1 in mouse cochlea and investigated the role of Bmi1 in hair cell survival. Bmi1 expressed in hair cells and supporting cells in mouse cochlea. Bmi1(-/-) mice displayed severe hearing loss and patched outer hair cell loss from postnatal day 22. Ototoxic drug-induced hair cells loss dramatically increased in Bmi1(-/-) mice compared with that in wild-type controls both in vivo and in vitro, indicating Bmi1(-/-) hair cells were significantly more sensitive to ototoxic drug-induced damage. Cleaved caspase-3 and TUNEL staining demonstrated that apoptosis was involved in the increased hair cell loss of Bmi1(-/-) mice. Aminophenyl fluorescein and MitoSOX Red staining showed the level of free radicals and mitochondrial ROS increased in Bmi1(-/-) hair cells due to the aggravated disequilibrium of antioxidant-prooxidant balance. Furthermore, the antioxidant N-acetylcysteine rescued Bmi1(-/-) hair cells from neomycin injury both in vitro and in vivo, suggesting that ROS accumulation was mainly responsible for the increased aminoglycosides sensitivity in Bmi1(-/-) hair cells. Our findings demonstrate that Bmi1 has an important role in hair cell survival by controlling redox balance and ROS level, thus suggesting that Bmi1 may work as a new therapeutic target for the prevention of hair cell death.

ApoE and S-100 expression and its significance in the brain tissue of rats with focal contusion.

This study explored the effect of focal cerebral contusion on the expression of ApoE and S-100, and its significance in determining the time of brain injury. Based on a rat model of cerebral contusion, immunohistochemistry was used to analyze the expressions of S-100 and ApoE at different time points after injury. Thirty minutes following cerebral contusion, ApoE protein expression was significantly increased in cortex neurons (P < 0.01), and S-100 protein expression was significantly (P < 0.001) elevated 2 h after cerebral contusion. Over time, the number of ApoE and S-100 positively expressing cells gradually increased. Three days after injury, ApoE was widely distributed throughout the tissue and the number of ApoE-positive cells and staining intensity reached a peak. ApoE expression decreased after this time point. Five days after cerebral contusion, the number of S-100-positive cells reached a peak level of expression higher than that in the control group. Our data demonstrate that the expression of ApoE and S-100 correlated with the progression of focal cerebral contusion. This suggests that both proteins may serve as effective biomarkers of focal cerebral contusions.

Genetic testing for sporadic hearing loss using targeted massively parallel sequencing identifies 10 novel mutations.

The genetic heterogeneity of non-syndromic hearing loss (NSHL) has hampered the identification of its pathogenic mutations. Several recent studies applied targeted genome enrichment (TGE) and massively parallel sequencing (MPS) to simultaneously screen a large set of known hearing loss (HL) genes. However, most of these studies were focused on familial cases. To evaluate the effectiveness of TGE and MPS on screening sporadic NSHL patients, we recruited 63 unrelated sporadic NSHL probands, who had various levels of HL and were excluded for mutations in GJB2, MT-RNR1, and SLC26A4 genes. TGE and MPS were performed on 131 known HL genes using the Human Deafness Panel oto-DA3 (Otogenetics Corporation., Norcross, GA). We identified 14 pathogenic variants in STRC, CATSPER2, USH2A, TRIOBP, MYO15A, GPR98, and TMPRSS3 genes in eight patients (diagnostic rate = 12.7%). Among these variants, 10 were novel compound heterozygous mutations. The identification of pathogenic mutations could predict the progression of HL, and guide diagnosis and treatment of the disease.

Lifelong exercise and locally produced insulin-like growth factor-1 (IGF-1) have a modest influence on reducing age-related muscle wasting in mice.

The age-related loss of skeletal muscle mass and function is termed sarcopenia and has been attributed to a decline in concentrations of insulin-like growth factor-1 (IGF-1). We hypothesized that constitutively expressed IGF-1 within skeletal muscles with or without exercise would prevent sarcopenia. Male transgenic mice that overexpress IGF-1 Ea in skeletal muscles were compared with wild-type littermates. Four-month-old mice were assigned to be sedentary, or had access to free-running wheels, until 18 or 28 months of age. In wild-type mice, the mass of the quadriceps muscles was reduced at 28 months and exercise prevented such loss, without affecting the diameter of myofibers. Conversely, increased IGF-1 alone was ineffective, whereas the combination of exercise and IGF-1 was additive in maintaining the diameter of myofibers in the quadriceps muscles. For other muscles, the combination of IGF-1 and exercise was variable and either increased or decreased the mass at 18 months of age, but was ineffective thereafter. Despite an increase in the diameter of myofibers, grip strength was not improved. In conclusion, our data show that exercise and IGF-1 have a modest effect on reducing aged-related wasting of skeletal muscle, but that there is no improvement in muscle function when assessed by grip strength.

Identification and characterization of rhizosphere fungal strain MF-91 antagonistic to rice blast and sheath blight pathogens.

AIM: To examine the inhibition effects of rhizosphere fungal strain MF-91 on the rice blast pathogen Magnaporthe grisea and sheath blight pathogen Rhizoctonia solani. METHODS AND RESULTS: Rhizosphere fungal strain MF-91 and its metabolites suppressed the in vitro mycelial growth of R. solani. The inhibitory effect of the metabolites was affected by incubation temperature, lighting time, initial pH and incubation time of rhizosphere fungal strain MF-91. The in vitro mycelial growth of M. grisea was insignificantly inhibited by rhizosphere fungal strain MF-91 and its metabolites. The metabolites of rhizosphere fungal strain MF-91 significantly inhibited the conidial germination and appressorium formation of M. grisea. Moreover, the metabolites reduced the disease index of rice sheath blight by 35·02% in a greenhouse and 57·81% in a field as well as reduced the disease index of rice blast by 66·07% in a field. Rhizosphere fungal strain MF-91 was identified as Chaetomium aureum based on the morphological observation, the analysis of 18S ribosomal DNA internal transcribed spacer sequence and its physiological characteristics, such as the optimal medium, temperature and initial pH for mycelial growth and sporulation production. CONCLUSIONS: Rhizosphere fungus C. aureum is effective in the biocontrolling of rice blast pathogen M. grisea and sheath blight pathogen R. solani both in in vitro and in vivo conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to show that rhizosphere fungus C. aureum is a potential fungicide against rice blast and sheath blight pathogens.

Heat stress induces epithelial plasticity and cell migration independent of heat shock factor 1.

Current cancer therapies including cytotoxic chemotherapy, radiation and hyperthermic therapy induce acute proteotoxic stress in tumour cells. A major challenge to cancer therapeutic efficacy is the recurrence of therapy-resistant tumours and how to overcome their emergence. The current study examines the concept that tumour cell exposure to acute proteotoxic stress results in the acquisition of a more advanced and aggressive cancer cell phenotype. Specifically, we determined whether heat stress resulted in an epithelial-to-mesenchymal transition (EMT) and/or the enhancement of cell migration, components of an advanced and therapeutically resistant cancer phenotype. We identified that heat stress enhanced cell migration in both the lung A549, and breast MDA-MB-468 human adenocarcinoma cell lines, with A549 cells also undergoing a partial EMT. Moreover, in an in vivo model of thermally ablated liver metastases of the mouse colorectal MoCR cell line, immunohistological analysis of classical EMT markers demonstrated a shift to a more mesenchymal phenotype in the surviving tumour fraction, further demonstrating that thermal stress can induce epithelial plasticity. To identify a mechanism by which thermal stress modulates epithelial plasticity, we examined whether the major transcriptional regulator of the heat shock response, heat shock factor 1 (HSF1), was a required component. Knockdown of HSF1 in the A549 model did not prevent the associated morphological changes or enhanced migratory profile of heat stressed cells. Therefore, this study provides evidence that heat stress significantly impacts upon cancer cell epithelial plasticity and the migratory phenotype independent of HSF1. These findings further our understanding of novel biological downstream effects of heat stress and their potential independence from the classical heat shock pathway.

Hyperbaric oxygen therapy in necrotising soft tissue infections: a study of patients in the United States Nationwide Inpatient Sample.

PURPOSE: Necrotising soft tissue infection (NSTI) is a deadly disease associated with a significant risk of mortality and long-term disability from limb and tissue loss. The aim of this study was to determine the effect of hyperbaric oxygen (HBO(2)) therapy on mortality, complication rate, discharge status/location, hospital length of stay and inflation-adjusted hospitalisation cost in patients with NSTI. METHODS: This was a retrospective study of 45,913 patients in the Nationwide Inpatient Sample (NIS) from 1988 to 2009. RESULTS: A total of 405 patients received HBO(2) therapy. The patients with NSTI who received HBO(2) therapy had a lower mortality (4.5 vs. 9.4 %, p = 0.001). After adjusting for predictors and confounders, patients who received HBO(2) therapy had a statistically significantly lower risk of dying (odds ratio (OR) 0.49, 95 % confidence interval (CI) 0.29-0.83), higher hospitalisation cost (US$52,205 vs. US$45,464, p = 0.02) and longer length of stay (LOS) (14.3 days vs. 10.7 days, p < 0.001). CONCLUSIONS: This retrospective analysis of HBO(2) therapy in NSTI showed that despite the higher hospitalisation cost and longer length of stay, the statistically significant reduction in mortality supports the use of HBO(2) therapy in NSTI.

Association between visceral obesity and sarcopenia and vitamin D deficiency in older Koreans: the Ansan Geriatric Study.

OBJECTIVES: To investigate whether vitamin D levels are independently associated with visceral obesity, sarcopenia, or sarcopenic obesity. DESIGN: Cross-sectional. SETTING: Population-based sample of elderly adults living in Ansan, Korea. PARTICIPANTS: Two hundred sixteen men and 268 women aged 65 and older. MEASUREMENTS: Serum 25-hydroxyvitamin D (25(OH)D) levels, visceral fat area (VFA) according to abdominal computed tomography scanning, and body composition (body fat percentage, appendicular skeletal muscle mass (ASM)) using dual-energy X-ray absorptiometry. Visceral obesity was defined as VFA of 100 cm(2) or greater and sarcopenia as ASM/height(2) more than 1 standard deviation (SD) below the sex-specific mean of a young reference group. RESULTS: The adjusted 25(OH)D level for men was negatively associated with systolic blood pressure, VFA, and body fat percentage but positively associated with ASM. In women, waist circumference, triglyceride levels, and VFA were negatively correlated with 25(OH)D levels. In the joint regression model, VFA and ASM were independently associated with 25(OH)D levels (ß = -0.078, P = .01 and ß = 0.087, P = .02, respectively) per 1SD difference in VFA and ASM in men but not women. When participants were categorized according to four visceral obesity and sarcopenia categories, adjusted mean 25(OH)D level was lower in men with visceral obesity than in men without but was not affected by the presence or absence of sarcopenia. CONCLUSION: Greater visceral fat and lower muscle mass were associated with lower 25(OH)D levels in elderly Korean men, suggesting that screening for vitamin D deficiency may be appropriate in older Koreans with visceral obesity or sarcopenia. Sarcopenic obesity as defined according to prespecified criteria did not have an additive association with 25(OH)D levels.

Responses of root hair development to elevated CO2.

This review highlights a potential signaling pathway of CO2-dependent stimulation in root hair development. Elevated CO2 firstly increases the carbohydrates production, which triggers the auxin or ethylene responsive signal transduction pathways and subsequently stimulates the generation of intracellular nitric oxide (NO). The NO acts on target Ca2+ and ion channels and induces activation of MAPK. Meanwhile, reactive oxygen species (ROS) activates cytoplasmic Ca2+ channels at the plasma membrane in the apex of the root tip. This complex pathway involves transduction cascades of multiple signals that lead to the fine tuning of epidermal cell initiation and elongation. The results suggest that elevated CO2 plays an important role in cell differentiation processes at the root epidermis.

Phosphorylation of spinal signaling-regulated kinases by acute uterine cervical distension in rats.

BACKGROUND: Spinal extracellular signaling-regulated kinase 1 and 2 (ERK 1/2) have been found to contribute to nociceptive processing, but the role of spinal ERK 1/2 in visceral pain related to the uterine cervix, the source of pain during the first stage of labor, is unknown. The aim of this study was to investigate ERK activation (phosphorylation) in spinal dorsal horn neurons after acute uterine cervical distension. METHODS: Under intraperitoneal anesthesia using chloral hydrate 300 mg/kg, female Sprague-Dawley rats were exposed to a 10-s uterine cervical distension of 25, 50, 75, and 100g or no distension (sham). The electromyographic response in the rectus abdominis muscle and mean arterial blood pressure and heart rate changes to uterine cervical distension were determined. The numbers of phosphorylated-ERK 1/2- immunoreactive (pERK 1/2-IR) dorsal horn neurons in cervical (C5-8), thoracic (T5-8), thoracolumbar (T12-L2) and lumbosacral (L(6)-S(1)) segments were counted using immunohistochemistry. RESULTS: Compared with the non-distended sham rats, uterine cervical distension resulted in a stimulus-dependent increase in electromyographic activity and the number of pERK-IR neurons that selectively located to the thoracolumbar segment, mostly in the deep dorsal and the central canal regions. The time course study demonstrated that spinal ERK activation peaked at 60 min with a slow decline for 120 min after uterine cervical distension stimulation. CONCLUSION: This study suggests that activation of spinal ERK might be involved in acute visceral pain arising from the uterine cervix.

Efficient, glucose responsive and islet-specific transgene expression by a modified rat insulin promoter.

This study was done to improve efficiency and islet specificity of the rat insulin promoter (RIP). Various RIP lengths were prepared and tested in vitro to drive luciferase reporter gene expression in INS1-cells, alpha-cells, acinar cells, ductal cells and fibroblasts. The CMV promoter was used as a positive control. In addition, the DsRed reporter gene was administered in vivo to rat pancreas by ultrasound-targeted microbubble destruction (UTMD). Confocal microscopy was used to detect the presence and distribution of DsRed within the pancreas after UTMD. A modified RIP3.1 promoter, which includes portions of the insulin gene after its transcription start site is fivefold more active in INS-1 cells than the full-length RIP promoter or the CMV promoter. RIP3.1 is regulated by glucose level and various islet transcription factors in vitro, and exhibits activity in alpha-cells, but not in exocrine cells. In vivo delivery of RIP3.1-DsRed resulted in expression of DsRed protein in beta-cells, and to a lesser extent in alpha-cells under normal glucose conditions. No DsRed signal was present in exocrine pancreas under RIP3.1. A modified RIP, RIP3.1, efficiently and specifically directs gene expression to endocrine pancreas.