Association between ADRB2 regulatory region polymorphisms and susceptibility to childhood asthma. / ADRB2åŸºå› è°ƒæŽ§åŒºå¤šæ€æ€§ä¸Žå„¿ç«¥å“®å–˜æ˜“æ„Ÿæ€§çš„ç›¸å ³æ€§ç ”ç©¶.

OBJECTIVES: To study the association of ß2-drenergic receptor (ADRB2) regulatory region single nucleotides polymorphism (SNP)/haplotypes at rs11168070, rs17108803, rs2053044, rs12654778, rs11959427, and rs2895795 loci with childhood asthma. METHODS: A total of 143 children with asthma who attended the hospital from October 2016 to October 2020 were enrolled as the asthma group, among whom 61 children had mild symptoms (mild group) and 82 children had moderate-to-severe symptoms (moderate-to-severe group). A total of 137 healthy children were enrolled as the control group. Peripheral venous blood samples were collected from the two groups. The SNaPshot SNP technique was used to analyze the SNP and haplotypes of the ADRB2 regulatory region at rs11168070, rs17108803, rs2053044, rs12654778, rs11959427, and rs2895795 loci in all children. The asthma group and the control group were compared in terms of the association of ADRB2 regulatory region SNP and haplotypes at the above six loci with susceptibility to asthma and severity of asthma. RESULTS: Polymorphisms were observed in the ADRB2 regulation region at the above six loci in both the asthma group and the control group, with significant differences between the two groups in the distribution of genotype and allele frequencies at rs2895795 (-1429T /A), rs2053044(-1023G/A), and rs12654778 (-654G/A) loci (P<0.05). Linkage disequilibrium of SNP was observed at the six loci of the ADRB2 regulatory region.The haplotypes of TATGCT, TATGGC, and AGTGCT were associated with susceptibility to childhood asthma, among which TATGCT and TATGGC were risk factors for childhood asthma (OR=1.792 and 1.946 respectively, P<0.05), while AGTGCT was a protective factor (OR=0.523, P<0.05). CONCLUSIONS: SNP/haplotype of the ADRB2 regulatory region is associated with the susceptibility to childhood asthma. The haplotypes of TATGCT and TATGGC formed by such SNP/haplotype are risk factors for childhood asthma, while AGTGCT is a protective factor.

[In vitro and in vivo anti-periodontitis effects of combination treatment of photodynamic and antibiotic therapies].

Objective: To investigate the effects of combination treatment of photodynamic therapy (PDT) based on photosensitizer chlorin e6 (Ce6) and antibiotic agent tinidazole (TNZ) against periodontitis both in vitro and in vivo. Methods: The Sprague-Dewley (SD) rat periodontitis model was constructed using the method of orthodontic wire ligation. After successful modeling, SD rats were randomly divided into the following 6 groups (3 rats in each group): positive control (Ctrl+), Ce6, TNZ, a mixture of Ce6 and TNZ (Ce6/TNZ), Ce6 with laser irradiation (Ce6+L), a mixture of Ce6 and TNZ with laser irradiation (Ce6/TNZ+L). Methyl thiazolyl tetrazolium (MTT) assay was used to assess the cytotoxic activities of Ce6 (concentration range: 0-20 mg/L), TNZ (concentration range: 0-16.6 mg/L) and their mixture (Ce6/TNZ) in mouse fibroblast L929 cells. Fluorescence probe method was applied to measure the production of reactive oxygen species in the dental plaque biofilms after various treatments with and without 5-minute laser irradiation at 635 nm at a power density of 0.5 W/cm2 (Ce6+L and Ce6/TNZ+L groups), thus to evaluate the PDT performances. Cell counting kit-8 (CCK-8) and live/dead staining were used to assess the antibacterial activity in each of the groups and the combination index (CI) of PDT combined with TNZ was calculated subsequently. Flow cytometry was utilized to detect the apoptosis-inducing effects of these treatments in macrophage RAW264.7 cells after processing with the apoptosis detection kit. The inhibitory effects of various treatments on the absorption of alveolar bone of SD rats were further evaluated in the periodontitis rats by using the micro-CT. Results: The survival rates of L929 cells in the preset concentration range were all above 90% in Ce6, TNZ and Ce6/TNZ groups. Upon laser irradiation, the plaque biofilms in Ce6 and Ce6/TNZ groups showed significant green fluorescence, indicating that large amounts of reactive oxygen species were triggered and generated significantly in the dental plaque biofilms. However, the survival rates of dental plaque microorganisms in 5 Ce6/TNZ concentrations were (85.4±5.5)%, (76.0±8.9)%, (61.7±0.6)%, (56.3±2.6)% and (43.5±0.6)% respectively, which were significantly lower than that in Ce6 only and TNZ only groups (P<0.01). The CI levle of each drug concentration group was less than 1.0, which showed a significant synergistic antibacterial efficiency. Stronger apoptotic activities were observed in Ce6+L and Ce6/TNZ+L groups compared with those in Ce6 only and Ce6/TNZ only groups (P<0.01). In periodontitis rats, Ce6/TNZ combined laser irradiation could effectively inhibit the absorption of alveolar bone. The alveolar bone volume and the ratio of bone volume and tissue volume were (1.49±0.07) mm3 and (47.08±0.71)%, respectively. The distances between cementoenamel junction to alveolar bone crest on buccal and palatal sites decreased to (2.13±0.07) mm and (1.94±0.10) mm respectively, showing a high inhibition efficiency. Conclusions: Ce6-mediated PDT combined with TNZ possessed notable synergistic effects against periodontitis, reflecting in the efficient antibacterial effect, the apoptosis-inducing action on macrophages, and the inhibitory efficacy on the alveolar bone absorption in vivo.

Thermophoretic collection of virus-laden (SARS-CoV-2) aerosols.

Detecting the existence of SARS-CoV-2 in the indoor atmosphere is a practical solution to track the prevalence and prevent the spread of the virus. In this work, a thermophoretic approach is presented to collect the novel coronavirus-laden aerosols from the air and accumulate to high concentrations adequate for the sensitivity of viral RNA detection. Among the factors, the density and particle size have negligible effects on particle trajectory, while the vertical coordinates of particles increase with the rise in heating source temperature. When the heating temperature is higher than 355 K , all of the particles exit the channel from one outlet; thus, the collecting and accumulating of virus-laden aerosols can be realized. This study provides a potential approach to accelerate the detection of SARS-CoV-2 and avoid a false negative in the following RNA test.

[Application research on carotid arterial shunting during simultaneous coronary artery bypass grafting and carotid endarterectomy].

Objective: The optimal operative strategy in patients with asymptomatic severe carotid artery stenosis undergoing coronary artery bypass grafting (CABG) is unknown. We sought to investigate the safety of carotid arterial shunting during simultaneous CABG and carotid endarterectomy (CEA). Methods: The clinical data of patients undergoing synchronous combined CEA and CABG in the First Hospital of China Medical University between March 2017 and July 2019 was retrospectively studied. Patients with asymptomatic severe carotid artery stenosis ≥70% according to NASCET (North American Symptomatic Carotid Endarterectomy Trial) were required CABG surgery. During conventional CEA, carotid arterial shunting was used in all cases. Results: Ten patients were recruited. The average clamping time of carotid artery was 5 minutes. The average follow-up time was 10 months. We did not observe stroke, cerebral hyper perfusion syndrome, death and carotid restenosis. Conclusions: Carotid arterial shunting during synchronous combined CEA and CABG was helpful for obtaining good curative effect.

Second-order cone programming with probabilistic regularization for robust adaptive beamforming.

Probabilistic regularization (PR) is introduced to make superdirective array beamforming robust against sensor characteristic mismatches. The objective is to enlarge the directivity while ensuring robustness with high probability. The PR problem is solved via the second-order cone programming where the regularization parameter is chosen through a statistical analysis of the system perturbations, based on Monte Carlo simulations. Experiments are carried out on a miniaturized 3 × 3 uniform rectangular array without calibration. The results show that for this particular array, the PR method is robust to sensor mismatches and achieves a higher level of directivity compared with other robust adaptive beamforming approaches.

An upper bound for the directivity index of superdirective acoustic vector sensor arrays.

Approximate analytical expressions of the white noise gain (WNG) for two superdirective acoustic vector sensor arrays are provided, which disclose the strong dependence of the tradeoff between the WNG and the directivity index (DI) on the highest order of the modes for the pattern synthesis. The considered arrays are a uniform linear array and a uniform circular array. A condition on the WNG that ensures a high array gain in the two-dimensional homogeneous and isotropic noise field is deduced. Using this condition, an upper bound on the highest order of the modes for the pattern synthesis can be derived, and hence the maximum DI can be determined. The presented results are not strictly limited to the two array geometries considered herein, and can be extended to other superdirective acoustic array designs.

Development and characterization of microsatellite markers for Ulmus chenmoui (Ulmaceae), an endangered tree endemic to eastern China.

Ulmus chenmoui (Ulmaceae) is an endangered tree found on Langya Mountain, eastern China. To better understand the population genetics of U. chenmoui and conserve the species, we developed microsatellite markers. Using a suppression-polymerase chain reaction technique, 74 compound microsatellite primer pairs were designed. Twelve microsatellite markers were polymorphic in 39 individuals, and the number of alleles per locus ranged from 3 to 9. The observed and expected heterozygosities ranged from 0.051 to 0.769 and from 0.533 to 0.768, respectively. Significant linkage disequilibrium was detected for three pairs of loci (P < 0.01), which may be due to a recent population bottleneck and the small population size. Nine of the 12 loci deviated from the Hardy-Weinberg equilibrium (P < 0.01), which could be explained by significant inbreeding rather than the presence of null alleles. These markers will provide a solid basis for future efforts in population genetic studies of U. chenmoui, which in turn will contribute to species conservation.

Low-frequency beamforming for a miniaturized aperture three-by-three uniform rectangular array of acoustic vector sensors.

This paper proposes a mode domain beamforming method for a 3 × 3 uniform rectangular array of two-dimensional (2D) acoustic vector sensors with inter-sensor spacing much smaller than the wavelengths in the working frequency band. The acoustic modes are extracted from the particle velocity observations in light of the source-sink pictures of the Taylor's series multipoles [Wikswo and Swinney, J. Appl. Phys. 56(11), 3039-3049 (1984)]. Then, similar to other mode domain methods, the modes are synthesized to obtain the desired beam pattern. The proposed method is limited to the cases where five is the maximum order of the modes for pattern synthesis, meaning that the directivity index in the 2D isotropic noise case can reach up to 10.4 dB. The proposed method has been validated by field experiments.

Eosinophilic esophagitis in children with esophageal atresia.

Eosinophilic esophagitis (EoE) has only rarely been reported in esophageal atresia (EA) patients. A retrospective case analysis of all EA patients born at our center between January 1999 and April 2012 was performed. A total of 113 of patients were identified; 10 patients were excluded as a result of inadequate data. Eighteen patients (17%) were diagnosed with EoE. The average number of eosinophilis was 30/high-power field (HPF) (19/HPF-80/HPF). The median age for diagnosis of EoE was 1 year and 6 months (8 months-8 years and 7 months). Children with EoE had a significantly greater incidence of reflux symptoms, dysphagia, tracheomalacia, and 'hypoxic spells' (P < 0.05). EoE patients also underwent significantly more surgery including fundoplication and aortopexy when compared with those without EoE (P < 0.0001). Although the incidence of gastrostomy was greater in the EoE group (33% vs. 13%), this was not statistically significant. Half of the EoE patients had a coexisting atopic condition at time of diagnosis. The commonest condition was asthma 7/18 (38%) followed by specific food allergy 6/18 (33%). EoE was treated in 11 patients with either swallowed fluticasone or budesonide slurry. All improved clinically. Histologically, five had complete resolution and six had partial improvement. Six children with EoE were treated with acid suppression alone. All improved clinically, and 5/6 had subsequent histological resolution. One child who received acid suppression and an exclusion diet also improved. Seven patients (38%) had an esophageal stricture at time of EoE diagnosis. Five were dilated at time of the initial endoscopy, prior to the diagnosis of EoE being available. Two patients had resolution of their strictures on medical treatment of their EoE alone and did not require further dilatation. EoE was seen in 17% of children with EA in this study. EoE should be considered in EA patients with persistent symptoms on standard reflux treatment, increasing dysphagia, and recurrent strictures.

Role of CD4+ CD25+ regulatory T cells in melatonin-mediated inhibition of murine gastric cancer cell growth in vivo and in vitro.

Melatonin is an important immune modulator with antitumor functions, and increased CD4(+) CD25(+) regulatory T cells (Tregs) have been observed in tumor tissues of patients and animal models with gastric cancer. However, the relationship between melatonin and Tregs remains unclear. To explore this potential connection, we performed an in vivo study by inoculating the murine foregastric carcinoma (MFC) cell line in mice and then treated them with different doses of melatonin (0, 25, 50, and 100 mg/kg, i.p.) for 1 week. The results showed that melatonin could reduce the tumor tissue and decrease Tregs numbers and Forkhead box p3 (Foxp3) expression in the tumor tissue. An in vitro study was also performed to test the effects of purified Tregs on melatonin-mediated inhibition of MFC cells. The cell cultures were divided into three groups: 1) MFC+ Tregs; 2) MFC only; and 3) MFC+CD4(+) CD25(-) T cells. After treatment with different concentrations of melatonin (0, 2, 4, 6, 8, and 10 mM) for 24 h, a dose-dependent apoptosis and cell cycle arrest at the G2/M phase was detected in melatonin-treated MFC at melatonin concentration higher than 4 mM. There were no significant differences in the rates of apoptosis and cell cycle distributions of MFC among the three groups. In conclusion, the antigastric cancer effect of melatonin is associated with downregulation of CD4(+) CD25(+) Tregs and its Foxp3 expression in the tumor tissue.

A method for acoustic parameter measurement of viscoelastic material.

A method for acoustic parameters measurement of viscoelastic material, using the directivity pattern of scattering field of spherical sample made by that material, had been presented. Aluminum spheres had been used for verification of the accuracy of this method, and the measurement results of a kind of rubber had been given. It shows that this method can be used to measure parameters of viscoelastic material in sufficient wide frequency range.

Perineal skin bridge and levator muscle preservation in neutral sagittal anorectoplasty (NSARP) for vestibular fistula.

The incision in limited posterior sagittal anorectoplasty for vestibular fistula (VF) extends from the coccyx to the fistula with the rectum identified by partial sagittal division of the levator muscle. In anterior sagittal anorectoplasty, the perineal incision extends from the fistula opening to the posterior margin of the external sphincter complex while preserving intact the levator muscle. We describe a modification of the operation for repair of VF, the neutral sagittal anorectoplasty (NSARP), which preserves both a perineal skin bridge between the neo-anus and the posterior fourchette and the levator muscle. Leaving the perineal skin bridge and the levator muscle intact could be important both from the aspects of perineal wound-healing and functional outcome. The skin incision in NSARP extends from the coccyx to the anterior limit of the external sphincter muscle complex as defined by muscle stimulation. An artery forceps passed through the VF facilitates the location and exposure of the rectum. The levator muscle is left intact. The dissection and closure of the VF is done entirely from within the opened rectum. There is an intact perineal skin bridge between the neo-anus and the posterior fourchette at the completion of the NSARP. In 12 consecutive patients with VF, NSARP prevented the risk of wound complications occurring between the neo-anus and the posterior fourchette. A diverting colostomy was safely avoided in our last five patients. NSARP does not involve any division of the levator muscle and it also retains an undisturbed wad of tissue that could function as the perineal body. All five patients who are 3 years or older demonstrate voluntary bowel movements. Preserving the perineal skin bridge and the levator muscle in NSARP have contributed to the improvement of aesthetic appearance of the perineum and faecal continence in our patients.

The management of combined oesophageal and duodenal atresia.

Duodenal atresia (DA) in babies with oesophageal atresia (OA) is associated with significant morbidity and mortality. The management protocol for this combination of anomalies is not well defined and evolving. The aim of this study was to review our experience with combined OA and DA and to note the evolving trend in management at Sydney Children's Hospital. Over the last 30 years, 225 babies with OA have been treated at our institution. Ten babies had associated DA. A total of 19 anomalies were noted; one child had multiple lethal anomalies and received no treatment. In three babies the diagnosis of associated DA was missed initially. For the nine babies who were treated, four had a primary OA repair followed by a delayed DA repair; one had cervical oesophagostomy, gastrostomy and DA repair; and two had a simultaneous repair of OA and DA with a gastrostomy. The last two patients in this series have had a primary simultaneous repair of both anomalies without a gastrostomy. The complications noted in the nine patients treated included anastomotic strictures in five, recurrent tracheo-oesophageal fistula in one, food bolus obstruction in one, and a megaduodenum requiring tapering in one. We believe that adopting a management protocol of primary simultaneous repair of both anomalies without a gastrostomy is justified. There was no apparent increase in morbidity and mortality with such an approach.

[Studies on the antigens of invasive stages of Plasmodium yoelii and Plasmodium berghei].

OBJECTIVE: To detect the rhoptry and surface proteins of invasive stages of Plasmodium yoelii and P. berghei with monoclonal antibodies. METHODS: Subcellular localization of antigens was detected by IFA. The antigens of different stages of the two species malaria parasites were analyzed by Western blotting. RESULTS: The antigens of rhoptry are very complicated. There are similar epitopes of the rhoptry proteins detected between the two species of Plasmodium. The similar epitopes were also detected between ookinetes and merozoites of P. yoelii, and ookinete antigens between the two species. But there are different antigens detected between merozoites and ookinetes in P. yoelii. The sporozoite surface antigen of P. yoelii was not detected in the ookinetes and merozoites in the same species. CONCLUSION: There are similar epitopes in the rhoptry and surface antigens of different stages and different species of rodent malaria parasites. There are also distinct antigens among them.

Isolated and multisystem hepatic trauma in children: the true role of non-operative management.

We retrospectively reviewed children with hepatic injuries (HI) admitted to our institutions from January 1982 to December 1999. Specific comparison was made of isolated (IHT) and multisystem hepatic trauma (MHT). Over the 18-year period 127 patients were identified with HI, 91 (71%) with MHT and 36 with IHT. The median age was 8 years (range 13 months to 14 years). Motor vehicle injury was the most common mechanism in both groups, but bicycle injuries were more common in IHT ( P<0.001). Shock ( P=0.02), the requirement for blood transfusion ( P<0.001), and operative intervention for the HI ( P=0.001) were all significantly more common in MHT. The distribution of liver injury grades was similar between the two groups. Twenty-two (17.3%) children died and in 18 the HI was the main cause or contributed significantly. There were 19 and 3 deaths in the MHT and IHT groups, respectively, a difference that was not significant. After excluding children with minor HI, 27 (39%) required operative intervention within 24 h of their injury. This suggests that the high success rate for non-operative management of HIs in the literature may have been biased by the inclusion of a significant proportion of subclinical injuries.

Identification of a novel membrane protein, HP59, with therapeutic potential as a target of tumor angiogenesis.

CM101, a polysaccharide isolated from the culture medium of Group B streptococcus, a neonatal pathogen, targets pathological angiogenesis and inhibits tumor growth in mice and humans. CM101 also targets neonatal lung and adult sheep lung endothelial cells. A gene encoding a transmembrane protein that interacts with CM101 was isolated from a sheep lung endothelial cell cDNA library. The gene, termed sp55, encodes a 495-amino acid polypeptide. COS-7 cells transfected with a vector containing sp55 express the SP55 protein-bound CM101 in a concentration-dependent manner. Stably transfected CHO cells also bound CM101. The corresponding human gene, hp59, was isolated from a human fetal lung cDNA library and had a predicted identity to SP55 of 86% over 495 amino acids. HP59 protein was shown by immunohistochemistry to be present in the pathological tumor vasculature of the lung, breast, colon, and ovary, but not in the normal vasculature, suggesting that the protein may be critical to pathological angiogenesis. The hp59 gene and/or the HP59 protein was not expressed in a variety of normal tissues, but was significantly expressed in human fetal lung, consistent with the pathophysiology of Group B streptococcus infections in neonates. Mice immunized with HP59 and SP55 peptides showed significant attenuation of tumor growth. Immunization effectively inhibited both the tumor angiogenesis and vasculogenesis processes, as evidenced by lack of both HP59- and CD34-positive vessels. These results and the immunohistochemistry data suggest a therapeutic potential for the CM101 target protein HP59 both as a drug target and as a vaccine against pathoangiogenesis.

Design and synthesis of a series of (2R)-N(4)-hydroxy-2-(3-hydroxybenzyl)-N(1)- [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide derivatives as potent, selective, and orally bioavailable aggrecanase inhibitors.

A pharmacophore model of the P1' site, specific for aggrecanase, was defined using the specificity studies of the matrix metalloproteinases and the similar biological activity of aggrecanase and MMP-8. Incorporation of the side chain of a tyrosine residue into compound 1 as the P1' group provided modest selectivity for aggrecanase over MMP-1, -2, and -9. A cis-(1S)(2R)-amino-2-indanol scaffold was incorporated as a tyrosine mimic (P2') to conformationally constrain 2. Further optimization resulted in compound 11, a potent, selective, and orally bioavailable inhibitor of aggrecanase.

Molecular mechanisms for aberrant expression of the human breast cancer specific gene 1 in breast cancer cells: control of transcription by DNA methylation and intronic sequences.

Breast cancer specific gene 1 (BCSG1), also referred as synuclein gamma, is the third member of a neuronal protein family synuclein. BCSG1 is not expressed in normal breast tissues but highly expressed in advanced infiltrating breast carcinomas. When over expressed, BCSG1 significantly stimulates breast cancer metastasis. To elucidate the molecular mechanisms underlying the abnormal transcription of BCSG1 in breast cancer cells, in this study, we isolated a 2195 base pair fragment of human BCSG1 gene. This fragment includes 1 kb 5'-flanking region, exon 1, and intron 1. By analysing the promoter activity and the methylation status of the exon 1 region, we show that (1) Intron 1 plays critical roles in the control of BCSG1 gene transcription through cis-regulatory sequences that affect BCSG1 transcription in cell type-specific and cell type-nonspecific manners. (2) The activator protein-1 (AP-1) is functionally involved in BCSG1 transcription in breast cancer cells through its binding to an AP-1 motif located in the intron 1. (3) The exon 1 region of BCSG1 gene contains a CpG island that is unmethylated in BCSG1-positive SKBR-3 and T47D cells but densely methylated in BCSG1-negative MCF-7 cells. (4) Treating MCF-7 cells with a demethylating agent 5-Aza-2'-deoxycytidine specifically activated BCSG1 transcription. Thus, our results suggest that while the cellular content of transcription activators and repressors that interact with the cis-regulatory sequences present in the intron 1 contribute prominently to the tissue-specific expression of BCSG1, demethylation of exon 1 is an important factor responsible for the aberrant expression of BCSG1 in breast carcinomas.

Early primary repair of long gap esophageal atresia: the VATER operation.

Despite the numerous approaches described for the management of neonates with "long gap" esophageal atresia, controversy still exists as to the preferred method. Delayed primary anastomosis is probably the most frequently adopted practice, but often the native esophagus is abandoned, and the long gap is bridged by some form of esophageal replacement. A case is reported of a 1.38-kg newborn with pure esophageal atresia and a long gap undergoing early primary repair. The technique used in this patient and the various options available for management of long-gap esophageal atresia are discussed.