Allergen detection and logistic multifactor analysis of allergic rhinitis.

OBJECTIVE: This study aims to investigate the allergens in children with allergic rhinitis (AR) and AR-related influencing factors. PATIENTS AND METHODS: The clinical data of 230 children with AR admitted to our hospital from June 2020 to June 2021 were retrospectively analyzed and included in the observation group. The clinical data of 230 healthy children during the same time period were included as the control group. All children had been tested for allergens using serum allergens, and the clinical data were collected by telephone questionnaires. Univariate and multivariate logistic regression were used to analyze the risk factors affecting AR. RESULTS: A total of 230 children with AR was included in this study, and some of them had two or more allergens. The proportion of house dust mite was the highest among the inhaled allergens, about 75.22%. Shrimp accounted for the highest proportion of food allergens, about 40.87%. Compared with the control group, the proportion of floating population, home heating, allergy history, asthma and other general information in the observation group was higher. At the same time, the proportion of environmental factors such as second-hand smoke, number of residents (≤ 3), daily ventilation and cleaning (no), domestic animals, domestic plants, decoration within 2 years, and living environment (rural) in the observation group was higher. In addition, the proportion of family factors such as delivery mode (cesarean section), family history of allergic rhinitis, parents' education level (middle school and above) in the observation group was higher (p < 0.05). Univariate logistic regression analysis showed that allergic history, asthma, second-hand smoke, floating population, number of residents, domestic animals, decoration within 2 years, delivery mode, and family history of allergic rhinitis were the risk factors affecting the incidence of AR in children (p < 0.05), and daily window ventilation and cleaning were the protective factors (p < 0.05). The multivariate logistic regression analysis showed that asthma, second-hand smoke, floating population, decoration within 2 years, family history of allergic rhinitis and domestic animals were independent risk factors for the occurrence of AR (p < 0.05), and daily ventilation and cleaning were protective factors for the occurrence of AR in children (p < 0.05). CONCLUSIONS: The proportion of house dust mite in inhalation allergens and shrimp in food allergens were the highest in AR children. The incidence of AR was closely related to asthma, second-hand smoke, floating population, decoration within 2 years, family history of AR and domestic animals, etc. Targeted measures could effectively prevent the occurrence and recurrence of AR. At the same time, daily ventilation and cleaning were the protective factors which could reduce the incidence and occurrence of AR in children.

[Nomogram analysis of risk factors for diabetic neuropathy in primary type 2 diabetic mellitus patients in Zhejiang Province].

Objective: To investigate the risk factors of diabetic nephropathy (DN) in primary type 2 diabetes mellitus (T2DM) patients and to quantitatively analyze the risk of DN by nomogram modeling. Methods: A total of 1 588 primary T2DM patients from 17 townships and streets in Zhejiang Province were enrolled from June 2018 to August 2018 in this cross-sectional study, with an average age of (56.8±10.1) years (50.06% male) and a mean disease duration of 9 years. The clinical data, biochemical test results, and fundus photographs of all T2DM patients were collected, and logistic regression analysis was used to screen the risk factors of DN. Then, a nomogram model was used to quantitatively analyze the risk of DN. Results: DN occurred in 27.71% (440/1 588 cases) primary type 2 diabetes patients. Hemoglobin A1c (HbA1c) (OR=1.159, 95%CI 1.039-1.292), systolic blood pressure (OR=1.041, 95%CI 1.031-1.051), serum creatinine (Scr) (OR=1.011, 95%CI 1.004-1.017), serum globulin (GLOB) (OR=1.072, 95%CI 1.039-1.105), diabetic retinopathy (DR) (OR=1.463, 95%CI 1.073-1.996), education level of more than junior high school (OR=2.018, 95%CI 1.466-2.777), and moderate-intensity exercise (OR=0.751, 95%CI 0.586-0.961) were influencing factors of DN. Nomogram model analysis showed that the total score of each factor of DN ranged from 64-138 points, and the corresponding risk rate ranged from 0.1-0.9. The nomogram model also predicted a C-index value of 0.753 (95%CI 0.726-0.781) and an area under the receiver operating characteristic curve of DN of 0.753. Internal verification of the C-index reached 0.738. The model displayed medium predictive power and could be applied in clinical practice. Conclusions: HbA1c, systolic blood pressure, Scr, GLOB, DR, and more than a junior high school education are independent risk factors of DN. Nomogram modeling can more intuitively evaluate the risk of DN in primary T2DM patients.

Association of genetic variants in the Sirt1 and Nrf2 genes with the risk of metabolic syndrome in a Chinese Han population.

BACKGROUND: Metabolic syndrome (MetS) is a complex of interrelated risk factors, including central adiposity, increased blood pressure, hyperglycemia, elevated triglyceride levels and low high-density lipoprotein. Few studies have reported the genetic variants in the Sirt1 and Nrf2 genes (Sirt1 rs7895833 A > G, Sirt1 rs2273773 C > T and Nrf2 rs6721961 C > A) that increase the risk of type 2 diabetes mellitus and are correlated with some glycemic and metabolic traits in the Chinese Han population. METHODS: Our study recruited 141 individuals with MetS and 549 individuals without MetS to investigate the associations between three single nucleotide polymorphisms (SNPs) of Sirt1 and Nrf2 and the risk of MetS in a Chinese Han population using the PCR-CTPP method. RESULTS: This research showed that the risk of MetS was 2.41 times higher for the AA genotype (P = 0.038) and 1.94 times higher for the AG genotype (P = 0.016) compared with carriers of the GG genotype. The serum levels of low-density lipoprotein cholesterol and HOMA-IR were significantly higher (P < 0.05) in carriers of the AA genotype of Sirt1 rs7895833 than in carriers of the AG and GG genotypes in the general population. The serum level of total cholesterol in the AA genotype was lower (P = 0.033) than that in the other two genotypes. However, the genotype frequencies of Sirt1 rs2273773 and Nrf2 rs6721961 in the MetS group were not significantly different from those in the control subjects, and those two genetic variants were not correlated with metabolic traits. CONCLUSIONS: These results underscore the contributions of SNPs of Sirt1 rs7895833 to MetS susceptibility as well as glycemic and metabolic traits in a Chinese population.

A targeted metabolomic profiling of plasma acylcarnitines in nonalcoholic fatty liver disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) has become a common liver disorder caused by lipid accumulation and insulin resistance (IR). Acylcarnitines have become a new biomarker of IR. However, their roles in NAFLD are still poorly studied. Thus, we performed a targeted metabolomic analysis to study the level of plasma acylcarnitines in patients with NAFLD. MATERIALS AND METHODS: The levels of 34 plasma acylcarnitines were measured by a targeted metabolomic approach in NAFLD patients (n = 50) and in healthy control subjects (n = 50) by liquid chromatography-tandem mass spectrometry. Detailed demographic and clinical characteristics of all subjects were also analyzed. RESULTS: The clinical presentation of IR was identified in the NAFLD group but not in the healthy control group. Significant differences were found in the levels of several short-, medium- and long-chain acylcarnitines. A high degree of correlation (r>0.7) was found between even-numbered-carbon long-chain acylcarnitines in NAFLD patients. The area under the receiver operator characteristic of long-chain acylcarnitines, especially C20 (AUC=0.952), C16:1 (AUC=0.949) and C14:1OH (AUC=0.944) acylcarnitines, was greater in NAFLD patients than in healthy control subjects. CONCLUSIONS: The accumulation and disorders of acylcarnitines are associated with NAFLD. A positive correlation between even-numbered-carbon long-chain acylcarnitines was found, and these even-numbered-carbon long-chain acylcarnitines. could be used as potential novel screening markers for nonalcoholic fatty liver disease.

[Current situation and health harmful effects of microplastics in the environment].

As an emerging environmental pollutant, microplastics have attracted more and more attention for its influence on the ecological environment and human health. Due to its wide range of usage and production, difficult degradation and other characteristics, as well as the continuous and substantial increase in the use of plastic products, the number of plastic fragments in the environment continues to increase, which leads to the accumulation of microplastics in the environment and organisms, spread through the food chain, and ultimately poses a threat to human health. At the same time, in the plastic production, synthetic textile, and other industries, the incidence of workers related occupational diseases greatly increased. In this paper, the concept, classification, source, impact on biological and human health of microplastics are summarized, and propose solutions on the current situation of microplastics pollution in China, we hope this review could provide effective reference for further carry out risk assessment of microplastics pollution on human health and formulate legislation to control microplastics pollution.

Parenchymal hyperdensity on C-arm CT images after endovascular therapy for acute ischaemic stroke predicts a poor prognosis.

AIM: To investigate whether hyperdense areas (HDAs) observed after endovascular treatment on multisection computed tomography (CT) are related to outcome. MATERIALS AND METHODS: Data on 82 patients with acute anterior circulation ischaemic stroke resulting from intracranial large artery occlusion were analysed retrospectively All patients underwent mechanical thrombectomy and/or emergency angioplasty, and partial or complete recanalisation was successfully achieved. C-arm CT was performed immediately after endovascular treatment for all patients. Clinical and radiological data were compared between patients with and those without HDA and between patients with good and those with poor outcomes. RESULTS: Compared with non-HDA patients, HDA patients were more likely to present with severe neurological deficits (admission National Institutes of Health Stroke Scale [NIHSS] score: 18 versus 16, p=0.037) and had a higher number of stent retriever passes performed (2.9±1.3 versus 1.4±1, p<0.001), longer onset-to-presentation times (229±78 versus 171±90 minutes; p=0.002), longer onset-to-recanalisation times (418±94 versus 331±105 minutes; p<0.001), and longer puncture-to-recanalisation times (103±47 versus 69±42 minutes; p=0.001). Fewer HDA patients had a good prognosis (35.7% versus 70%, p<0.001). Multivariate analysis showed the presence of HDAs was an independent negative prognostic factor (OR=0.208; p=0.002). CONCLUSION: HDAs on C-arm CT appear to be common in patients with acute ischaemic stroke who underwent successful endovascular treatment. HDA presence suggests a poor prognosis despite successful reperfusion.

Uterine preservation in a young patient with adenosarcoma of the uterus - Case report and review of literature.

•A young lady with uterine sarcoma had a successful delivery 3 years after diagnosis.•Local recurrence occurred after 8 years.•Ultrasound and endometrial biopsy can be used in the follow-up of these patients.•Patients should be counselled on risk of late recurrence.

[Etiological analysis and establishment of a discriminant model for lower respiratory tract infections in hospitalized patients].

Objective: To analyze the pathogens of lower respiratory tract infection(LRTI) including bacterial, viral and mixed infection, and to establish a discriminant model based on clinical features in order to predict the pathogens. Methods: A total of 243 hospitalized patients with lower respiratory tract infections were enrolled in Fujian Provincial Hospital from April 2012 to September 2015. The clinical data and airway (sputum and/or bronchoalveolar lavage) samples were collected. Microbes were identified by traditional culture (for bacteria), loop-mediated isothermal amplification(LAMP) and gene sequencing (for bacteria and atypical pathogen), or Real-time quantitative polymerase chain reaction (Real-time PCR)for viruses. Finally, a discriminant model was established by using the discriminant analysis methods to help to predict bacterial, viral and mixed infections. Results: Pathogens were detected in 53.9% (131/243) of the 243 cases.Bacteria accounted for 23.5%(57/243, of which 17 cases with the virus, 1 case with Mycoplasma pneumoniae and virus), mainly Pseudomonas Aeruginosa and Klebsiella Pneumonia. Atypical pathogens for 4.9% (12/243, of which 3 cases with the virus, 1 case of bacteria and viruses), all were mycoplasma pneumonia. Viruses for 34.6% (84/243, of which 17 cases of bacteria, 3 cases with Mycoplasma pneumoniae, 1 case with Mycoplasma pneumoniae and bacteria) of the cases, mainly Influenza A virus and Human Cytomegalovirus, and other virus like adenovirus, human parainfluenza virus, respiratory syncytial virus, human metapneumovirus, human boca virus were also detected fewly. Seven parameters including mental status, using antibiotics prior to admission, complications, abnormal breath sounds, neutrophil alkaline phosphatase (NAP) score, pneumonia severity index (PSI) score and CRUB-65 score were enrolled after univariate analysis, and discriminant analysis was used to establish the discriminant model by applying the identified pathogens as the dependent variable. The total positive predictive value was 64.7%(77/119), with 66.7% for bacterial infection, 78.0% for viral infection and 33.3% for the mixed infection. Conclusions: The mostly detected pathogens were Pseudomonas aeruginosa, atypitcal pathogens, Klebsiella pneumoniae, influenza A virus and human cytomegalovirus in hospitalized patients with LRTI in this hospital. The discriminant diagnostic model established by clinical features may contribute to predict the pathogens of LRTI.

Pleckstrin homology-like domain family B member 1 rs498872 polymorphism and glioma risk in Chinese Han population.

This case-control study aimed to investigate the association between PHLDB1 rs498872 polymorphism and the risk of glioma in a Chinese Han population. A total of 210 patients and 235 controls were enrolled in this study. The CT genotype and TT genotype were significantly associated with the risk of glioma (OR=1.48, 95%CI 1.00-2.19, P=0.05 and OR=2.40, 95%CI 1.06-4.10, P=0.03), respectively. In addition, T allele of PHLDB1 rs498872 polymorphism was significantly associated with an increased risk of glioma (OR=1.58, 95%CI 1.08-2.29, P=0.02). We also found that PHLDB1 rs498872 polymorphism was not associated with histology and tumor grade of glioma. In conclusion, this study found that PHLDB1 rs498872 polymorphism was significantly associated with glioma risk in Chinese Han population.

[Influence of short-term intensive insulin therapy on plasma concentration of lipoprotein-associated phospholipase A(2) and secretory phospholipase A(2) in newly diagnosed type 2 diabetic patients].

The aim of the study was to explore the effect and its clinical relevance of short-term intensive insulin treatment on plasma concentrations of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and secretory phospholipase A(2) (sPLA(2)) in newly diagnosed type 2 diabetes mellitus (T2DM). Ninety newly diagnosed T2DM patients were recruited and received continuous subcutaneous insulin infusion (CSII) for about 2 weeks. After CSII, sPLA(2) levels [173.78 (80.95, 278.09) µg/L] were significantly decreased compared with the levels before [219.33 (130.03, 337.30) µg/L], P<0.01, while no statistic significant changes could be viewed in Lp-PLA(2) levels. Correlation analysis showed that the changes of Lp-PLA(2) and sPLA(2) were both positively correlated with the changes of homeostasis model assessment of insulin resistance(HOMA-IR)after CSII (r=0.537, 0.493 respectively, all P<0.05). The Lp-PLA(2) and sPLA(2) level reduction after CSII might help to protect the patients from diabetic macroangiopathy. Trial registration Chinese Clinical Trial Registry, ChiCTR-TRC-10001618.

Distribution of LIM domain kinase 1 in the olfactory bulb, cerebral cortex, hippocampus, and cerebellum of the App/PS+/- mice.

LIM domain kinase 1 (LIMK1), an actin-binding kinase, can phosphorylate and inactivate its substrates, and can regulate long-term memory and synaptic plasticity. Both ß-amyloid precursor protein (App) and presenilin (PS) are functional degeneration factors during early neuronal development, and are considered as potential factors that contribute to the development of Alzheimer's disease (AD). However, hardly any information is available about the distribution and expression of LIMK1. Thus, using the App and PS deficient mice, the role of LIMK1 was demonstrated in the absence of App and PS. Our results showed that LIMK1 was present in the nerve fiber layer and external plexiform layer of the olfactory bulb, as well as in the mitral cells and Purkinje cells of the cerebellum in App and PS deficient mice. Additionally, LIMK1 was concentrated in the granule cell layer of the olfactory bulb and cerebellum and LIMK1 positive cells were located in the CA1 region of the hippocampus. Our study indicates that there is a connection between LIMK1 and AD in the mouse model of AD. This might explain neurological problems such as cerebellar ataxia, impaired long-term memory, and impaired synaptic plasticity observed in AD.

Mutations of transglutaminase-1 in Chinese patients with autosomal recessive congenital ichthyosis: a case report with clinical and genetic analysis of Chinese cases reported in literature.

BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of diseases of keratinization, characterized primarily by abnormal skin scaling over the whole body surface. Recently, ARCI has been designated to include the major forms of lamellar ichthyosis (LI), congenital ichthyosiform erythroderma (CIE) and harlequin ichthyosis. The first two conditions are the most common major clinical subtypes, and both are caused principally by mutations in the transglutaminase 1 gene, TGM1, although other genes may be responsible in some cases. AIM: To identify the genetic mutations underlying LI in a Chinese family with LI, and to review all the known TGM1 mutations in Chinese patients with ARCI. METHODS: The proband had the severe classic LI phenotype, and was a member of a four-generation family with close blood relationships. We sequenced the DNA of the patients and close relatives. We also reviewed 13 Chinese patients with ARCI from 8 reported families, comprising 10 patients with LI, 2 with CIE and 1 with bathing suit ichthyosis. RESULTS: We characterized 14 different TGM1 mutations. Six of these were reported in other ethnic groups initially and later in Chinese patients, while the remaining eight were first described in Chinese patients. Of the latter, five have been reported only in Chinese patients, while the remaining three have also been reported in other ethnic groups. CONCLUSION: This study expands the current spectrum on TGM1 mutation and increases the knowledge of TGM1 mutation characteristics.

Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide.

The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 µg/kg rhBNP and those in the high-dose group (n=8) received 45 µg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

A novel CB receptor GPR55 and its ligands are involved in regulation of gut movement in rodents.

BACKGROUND: This study was to investigate the effects of the novel cannabinoid receptor - G protein-coupled receptor 55 (GPR55) - and its ligands O-1602 and cannabidiol (CBD) on gastrointestinal (GI) motility in rodents. METHODS: Lipopolysaccharide (LPS) was used in vivo to produce the model of septic ileus. The intestinal motility was measured by recording myoelectrical activity of jejunum in rats, and by measuring GI transit with a charcoal marker in mice, in presence of O-1602 or CBD. Inflammatory response was assessed serologically and histologically. The expression and distribution of GPR55 in the different parts of rat intestine were investigated by real-time PCR and immunohistochemistry. In vitro, the effects of the drugs on the GI movement were investigated by measuring the contraction of the intestinal muscle strips in organ bath, and the intracellular responses of the muscle cells with microelectrode technique. KEY RESULTS: G protein-coupled receptor 55 was expressed in different parts of rat intestine. Lipopolysaccharide significantly inhibited the intestinal motility, increased inflammatory cytokines and GPR55 expression. Pretreatment with CBD normalized LPS-induced hypomotility and improved the inflammatory responses serologically and histologically. Both O-1602 and CBD counteracted LPS-induced disturbances of the gut contraction, but had no effect on the membrane potential of the muscle cells, while cannabinoid type 1 receptor antagonist AM251 and cannabinoid type 2 receptor antagonist AM630 increased the potential. CONCLUSIONS & INFERENCES: G protein-coupled receptor 55 existed throughout the whole intestine of rats. O-1602 or CBD selectively normalized the motility disturbances. Possible mechanisms involved systemic anti-inflammation and the regulation of myoelectrical activity of the intestine.

Ante-partum and post-partum markers of metabolic syndrome in pre-eclampsia.

It is rare for a study to address immediate metabolic change in pre-eclamptic pregnancy. Our aim is to study the ante-partum and post-partum metabolic markers in pre-eclampsia. A total of 33 pre-eclamptic and 200 uncomplicated women with singleton pregnancies were recruited for the prospective research. Immediately ante-partum and 24-48 h postpartum venous blood samples were collected for the analysis of metabolic markers. In the pre-eclamptic group, the ante-partum fasting glucose, fasting insulin, triglyceride and free fatty acid levels were found to be higher than in the control group; however, ante-partum high-density lipoprotein level was lower. Interestingly, fasting glucose and insulin levels decreased by 24-48 h post-partum in both groups and no significant differences were found. Pre-eclamptic patients had lower post-partum high-density lipoprotein (P=0.02), higher triglyceride (P<0.001), higher free fatty acid (P=0.02) and higher apolipoprotein B levels (P=0.01) than the control group. Dyslipidemia lasts from ante-partum to immediate post-partum in pre-eclamptic women in the form of increased triglyceride, higher free fatty acid and decreased high-density lipoprotein levels. We speculate that women with dyslipidemia and higher baseline blood pressure tend to develop pre-eclampsia during pregnancy. Hence, the development of pre-eclampsia may be a 'marker' of possible future cardiovascular or metabolic disease.

Subconjunctival gene delivery of the transcription factor GA-binding protein delays corneal neovascularization in a mouse model.

Corneal neovascularization can reduce visual acuity. GA-binding protein (GABP) is a transcription factor that regulates the expression of target genes including vascular endothelial growth factor (VEGF) and roundabout4 (Robo4), which participate in pathologic angiogenesis. We assessed whether intraocular injection of the GABP gene affects the growth of new corneal blood vessels in a mouse ocular neovascularization model. Transfection of human GABPalpha and GABPbeta gene (GABPalpha/beta) into human conjunctival epithelial cells resulted in decreased VEGF and Robo4 expression. Three groups of mice underwent chemical and mechanical denudation of the corneal epithelium. Subsequently, two groups were administered subconjunctival injection of lipoplexes carrying plasmid DNA encoding for human GABPalpha/beta or an empty plasmid DNA at 1-week intervals. The third group served as an experimental control. In vivo delivery of human GABPalpha/beta into mouse neovascularized cornea reduced VEGF and Robo4 gene expression. Biomicroscopic examination showed that, at 1 week after one or two injections, GABPalpha/beta-treated eyes had significantly less neovascularized corneal area than did eyes treated with the empty vector. Histologic examination showed significantly less vascularized area and fewer blood vessels in the GABP-treated group at 1 week after injections. However, these angiosuppressive effects were weakened at 2 weeks after injections. Our results indicate that subconjunctival GABP gene delivery delays corneal neovascularization for up to 2 weeks in a mouse model of deliberate corneal injury.

Synergistic therapeutic effect of arsenic trioxide and radiotherapy in BALB/C nude mice bearing nasopharyngeal carcinoma xenografts.

UNLABELLED: It has been shown that arsenic trioxide (ATO) induced apoptosis in human nasopharyngeal carcinoma cells and inhibited the growth of nasopharyngeal carcinoma xenografts (NPCX) in nude mice. AIM: The present study was designed to determine whether ATO at the non-toxic dose level could potentiate the therapeutic effectiveness of radiation therapy in nasopharyngeal carcinoma, using a BALB/C nude mouse xenograft model. METHODS: The mice bearing NPCX were treated with radiation alone (2, 4, and 6 Gy), ATO alone (4 mg/kg/day x 6 days), and ATO plus radiation at the same dosage levels. Time of tumor growth delay (defined as the time necessary for the tumor to grow four-fold of its initial volume after, compared with untreated tumors) and toxic effects were determined. RESULTS: The low dose ATO alone has no pronounced effects on tumor growth delay compared to untreated control. However, compared with radiation alone, the combined regimen delayed the tumor growth by 2-10 days and had no significant toxic effects such as the liver function damage. CONCLUSIONS: Combination of ATO at non-toxic dose level and radiation has synergistic effects on tumor growth inhibition in vivo and is well tolerated.

Mutations in the ATP2C1 gene in Chinese patients with Hailey-Hailey disease.

Hailey-Hailey disease (HHD; MIM 16960) is a rare autosomal dominant hereditary disorder characterized by recurrent eruption of vesicles and bullae, predominantly involving the body folds. It is caused by heterozygous mutations in the ATP2C1 gene, encoding the human secretory pathway Ca2+/Mn2+-ATPase protein 1 (hSPCA1). When we studied Chinese patients with HHD, we found two different heterozygous mutations, Q506X and G353V, the former previously reported in a Hungarian patient, and the latter being a novel mutation. In a 38-year-old patient from a four-generation pedigree with a 3-year history of severe recurrent blisters, we identified a C-->T transition at nucleotide 1696, c(1696C-->T), in exon 17 of ATP2C1, resulting in a nonsenes mutation, Gln506X, which resulted in a premature termination codon. In the second patient, who represented a occurrence of sporadic Hailey-Hailey disease, a G-->T transversion of nucleotide, c(G1238T), in exon 13 of ATP2C1 was detected, which resulted in a Gly353-->Val amino acid substitution (G353V). Our molecular findings further demonstrate that the mutational events in the human ATP2C1 gene encoding the hSPCA1 pump play an important role in the pathogenesis of HHD.