[Research advances on the role and mechanism of microRNA in hypertrophic scar].

Hypertrophic scar (HS) affects the function and beauty of patients, and brings a heavy psychological burden to patients. However, the specific pathogenesis mechanism of HS in molecular biology level is not yet clear, and this disease is still one of the clinical diseases difficult to prevent and cure. MicroRNA (miR) is a family of single-stranded endogenous noncoding RNAs that can regulate gene expression. The abnormal transcription of miR in hypertrophic scar fibroblasts can affect the transduction and expression of downstream signal pathway or protein, and the exploration of miR and its downstream signal pathway and protein helps deeply understand the occurrence and development mechanism of scar hyperplasia. This article summarized and analyzed how miR and multiple signal pathways involve in the formation and development of HS in recent years, and further outlined the interaction between miR and target genes in HS.

Safety and efficacy of oral lopinavir/ritonavir in pediatric patients with coronavirus disease: a nationwide comparative analysis.

OBJECTIVE: Because of the limited treatment options available, oral lopinavir/ritonavir (LPR) was used for treating coronavirus disease (COVID-19) in pediatric patients. This study aimed to assess the efficacy and safety of LPR in COVID-19 pediatric patients with mild symptoms. PATIENTS AND METHODS: This retrospective multicenter analysis included hospitalized children with mild COVID-19 who received LPR at one of 13 hospitals in China from January 1, 2020, to June 1, 2020. Patients treated with LPR were matched with patients not treated with LPR (1:4) according to age, sex, and length of symptom onset and hospitalization. Descriptive statistics and non-parametric tests were applied to compare differences between groups. Kaplan-Meier probability curves and Cox regression models were used to analyze nasal swab turning negative time (recovery time) and hospital discharge days. RESULTS: In total, 23 patients treated with LPR were matched with 92 untreated controls. The median age of patients was 6 years, and 56.52% of them were male. All patients were discharged from the hospital after being cured. The treatment group had a longer nasal swab turning negative time (hazard ratio [HR] 5.33; 95% CI: 1.94-14.67; p = 0.001) than the control group. LPR treatment was also associated with a longer hospitalization time (HR 2.01; 95% CI: 1.24-3.29; p = 0.005). After adjusting for the influence of LPR treatment, adverse drug reaction events were associated with a longer nasopharyngeal swab negative time (HR 4.67; 95% CI 1.35-16.11; p = 0.015). CONCLUSIONS: For children with mild COVID-19, LPR is inferior to conventional treatment in reducing virus shedding time and hospitalization duration and is associated with increased adverse reactions.

Concentration changes in gemcitabine and its metabolites after hyperthermia in pancreatic cancer cells assessed using RP-HPLC.

BACKGROUND: Gemcitabine (2',2'-difluoro-2'-deoxycytidine;dFdC) is a first-line chemotherapy drug for pancreatic cancer. Recently, a synergistic anti-tumor treatment of dFdC and hyperthermia has achieved good clinical results, but there are few reports on the molecular mechanism influenced by hyperthermia. This study is an initial exploration of the effects of hyperthermia on changes in the concentration of dFdC and its metabolites in pancreatic cancer cells. The aim is to provide a theoretical basis for clinical detection and pharmacokinetic research. METHODS: PANC-1 cells at logarithmic growth phase were used as the experimental object. The MTT assay was performed to determine the half maximal inhibitory concentration (IC50) of dFdC. After PANC-1 cells were cultured in DMEM medium containing IC50dFdC and treated with hyperthermia at 41 °C or 43 °C, changes in the concentration of dFdC, 2',2'-difluorodeoxyuridine (dFdU) and difluorodeoxycytidine triphosphate (dFdCTP) in the cells were tested using an optimized reverse phase high-performance liquid chromatography (RP-HPLC) protocol. RESULTS: We found that 41 °C and 43 °Chyperthermia gave rise to a decrease in dFdC and dFdU content. At 41 °C, the levels respectively fell to 9.28 and 30.93% of the baseline, and at 43 °C, to 24.76 and 57.80%, respectively. The dFdCTP content increased by 21.82% at 41 °C and 42.42% at 43 °C. CONCLUSION: The two heat treatments could alter the mechanism of dFdC metabolism in PANC-1 cells. The effect of 43 °C hyperthermia is more significant. Our observations may be instrumental to explaining the higher anti-tumor efficacy of this combination therapy.

Estimation of Lung Volume in Normal Population Using MSCT.

OBJECTIVES: To estimate lung volume in normal population by a combination of multi-slice spiral CT and Pulmo software. METHODS: Scans of the lung were performed on 45 normal individuals using Emotion 16-slice spiral CT and Pulmo software. A measurement instrument of work station was used to measure the vertical diameter of left and right lungs, the maximum anteroposterior and transverse diameters at the layers of apex pulmonis 1 cm below, arcus aortae, subcarinal and diaphragmatic dome, and the lung volume. Regression analysis was performed on normal lung volume and each measured parameter by SPSS 20.0 and an optimal model was selected. RESULTS: The goodness of fit between the best curvilinear equations of the normal bilateral lung volumes was 0.981. The goodness of fit between the curvilinear equations of the normal bilateral lung volume and the product of the vertical diameter and the maximum transverse diameter of diaphragmatic dome were 0.977 and 0.972, respectively. Fifteen cases were selected to make a retrospective test on the 3 models. No significant difference was found between the estimated and measured with Pulmo software lung volumes. CONCLUSIONS: The normal lung volume before injury can be estimated by the curvilinear equations established in this study. The percentage of lung compression can be measured based on the volume of compressed lung, which can provide a reference for the identification of lung compression degree.

[Epidemiological and clinical characteristics of 109 patients with crayfish-related rhabdomyolysis].

A total of 109 in patients with crayfish-related rhabdomyolysis were enrolled in our hospital from July to August 2016,including 31.2%(34/109)males and 68.8% (75/109)females.The number of home-cooked crayfish accounted for 60.6% (66/109). Main symptom was back pain 96.3% (105/109). The misdiagnosis rate was 15.6% (17/109). On day 1, 2, 3 after admission and the day before discharge,serum creatine kinase were 1 175(446, 2 258)IU/L,3 710(2 137, 8 875)IU/L,1 899(1 063, 4 595)IU/L and 317(152, 532)IU/L,respectively(P<0.001).Serum myoglobin were (603±484)µg/L,(313±284)µg/L,(104±74)µg/L and (55±20)µg/L,respectively(F=39.1, P<0.001).Females were more susceptible to crayfish-related rhabdomyolysis. Home-cooked crayfish is prone to induce rhabdomyolysis and easily to be misdiagnosed. Creatine kinase and myoglobin showed characteristic dynamic changes.

Classification and phylogenetic analysis of Chinese hawthorn assessed by plant and pollen morphology.

The Chinese hawthorn (Crataegus pinnatifida Bge. var. major N.E.Br.) is uniquely originated in northern China. The ecological and horticultural importance of Chinese hawthorn is considerable and some varieties are valued for their fruit or medicine extracts. Its taxonomy and phylogeny remain poorly understood. Apart from general plant morphological traits, pollen is an important trait for the classification of plants and their evolutionary origin. However, few studies have investigated the pollen of Chinese hawthorn. Here, an analysis of plant and pollen morphological characteristics was conducted in 57 cultivars from the Shenyang region. Thirty plant morphological characters and nine pollen grain characters were investigated. The plant morphological analysis revealed that the coefficient of variation for 13 traits was >20%, which indicates a high degree of variability. We also found that the pollen grains varied greatly in size, shape (from prolate to perprolate), and exine pattern (striate-perforate predominantly). The number of apertures was typically three. Based on these findings, we suggest that pollen morphology associated with plant morphological traits can be used for classification and phylogenetic analysis of Chinese hawthorn cultivars. In sum, our results provide new insights and constitute a scientific basis for future studies on the classification and evolution of Chinese hawthorn.

Anxiety and depression with neurogenesis defects in exchange protein directly activated by cAMP 2-deficient mice are ameliorated by a selective serotonin reuptake inhibitor, Prozac.

Intracellular cAMP and serotonin are important modulators of anxiety and depression. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI) also known as Prozac, is widely used against depression, potentially by activating cAMP response element-binding protein (CREB) and increasing brain-derived neurotrophic factor (BDNF) through protein kinase A (PKA). However, the role of Epac1 and Epac2 (Rap guanine nucleotide exchange factors, RAPGEF3 and RAPGEF4, respectively) as potential downstream targets of SSRI/cAMP in mood regulations is not yet clear. Here, we investigated the phenotypes of Epac1 (Epac1(-/-)) or Epac2 (Epac2(-/-)) knockout mice by comparing them with their wild-type counterparts. Surprisingly, Epac2(-/-) mice exhibited a wide range of mood disorders, including anxiety and depression with learning and memory deficits in contextual and cued fear-conditioning tests without affecting Epac1 expression or PKA activity. Interestingly, rs17746510, one of the three single-nucleotide polymorphisms (SNPs) in RAPGEF4 associated with cognitive decline in Chinese Alzheimer's disease (AD) patients, was significantly correlated with apathy and mood disturbance, whereas no significant association was observed between RAPGEF3 SNPs and the risk of AD or neuropsychiatric inventory scores. To further determine the detailed role of Epac2 in SSRI/serotonin/cAMP-involved mood disorders, we treated Epac2(-/-) mice with a SSRI, Prozac. The alteration in open field behavior and impaired hippocampal cell proliferation in Epac2(-/-) mice were alleviated by Prozac. Taken together, Epac2 gene polymorphism is a putative risk factor for mood disorders in AD patients in part by affecting the hippocampal neurogenesis.

Genetic variability and diversity of the main resources of lily assessed via phenotypic characters, pollen morphology, and ISSR markers.

Lily (Lilium spp), which belongs to Lilium, is one kind of monocotyledon. As a perennial ornamental plant with extremely high esthetic, edible, and medicinal value, lily has gained much favor due to its mostly showy flowers of various colors and elegant shape. In this research, we studied experimental materials in a sample of 49 individuals including 40 cultivars, nine species of wild lily, and their variants. The collection of 40 cultivars covered all six hybrids in the genus, i.e., Asiatic hybrids, Oriental hybrids, Longiflorum hybrids, LA hybrids, LO hybrids, and OT hybrids. Genetic diversity and inter-relationships were assessed through analysis of phenotypic characteristics, pollen morphology, and ISSR molecular markers. Quantitative characters were selected to analyze phenotypic variation, with results indicating greater variability in petiole length as compared to other characters. Pollen morphological observations suggested that the largest variation coefficient between all hybrids and wild species was the lumina. ISSR makers demonstrated that both cultivars and wild species possess a high level of genetic diversity. Specifically, the genetic diversity of wild lily was higher than cultivars.

[Relationship between the Expression of α-syn and Neuronal Apoptosis in Brain Cortex of Acute Alcoholism Rats].

OBJECTIVES: To observe the changes of expression of α-synuclein （α-syn） and neuronal apoptosis in brain cortex of acute alcoholism rats and to explore the mechanism of the damage caused by ethanol to the neurons. METHODS: The model of acute alcoholism rat was established by 50% alcohol gavage. The α-syn and caspase-3 were detected by immunohistochemical staining and imaging analysis at 1 h, 3 h, 6 h and 12 h after acute alcoholism. The number of positive cell and mean of optical density were detected and the trend change was analyzed. The variance analysis and t-test were also performed. RESULTS: The number of α-syn positive cell and average optical density in brain cortex of acute alcoholism rat increased significantly and peaked at 6 hour with a following slight decrease at 12 h, but still higher than the groups at 1 h and 3 h. Within 12 hours after poisoning, the number of caspase-3 positive cell and average optical density in brain cortex of rats gradually increased. CONCLUSIONS: The abnormal aggregation of α-syn caused by brain edema and hypoxia may participate the early stage of neuronal apoptosis in brain cortex after acute alcoholism.

Chronic necrotizing pulmonary aspergillosis in an immunocompetent patient: report of a rare case.

Chronic necrotizing pulmonary aspergillosis (CNPA) is a relatively uncommon manifestation of infection with Aspergillus spp. which mainly affects immunocompromised or immunostressed individuals with underlying lung diseases. Here, we present a case of mediastinum-involved CNPA in an immunocompetent patient with no symptoms and previous good health.

Second-line pemetrexed versus docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer: a randomized, open-label study.

INTRODUCTION: This randomized, open-label study compared pemetrexed versus docetaxel as second-line therapy for Chinese patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The primary endpoint tested non-inferiority of overall survival (OS) on the combined data from these patients and those in the global registration trial. Data from patients in the current study only (Chinese patients) were the basis for the study's secondary objectives. METHODS: Patients with stage IIIB/IV disease were randomized (1:1) to receive pemetrexed (500 mg/m(2); 107 randomized; 106 treated) or docetaxel (75 mg/m(2); 104 randomized; 102 treated) on Day 1 of each 21-day cycle. Treatment continued until progressive disease, unacceptable toxicity or patient/investigator decision. All efficacy and safety data were analyzed at the pre-specified study completion; supplementary OS analyses were performed later, after additional events had been recorded. RESULTS: The primary endpoint of OS noninferiority of pemetrexed to docetaxel was not met, the lower CL was <50% and P>0.025 (efficacy retained=97.9% [95% CLs: 47.1, 141.9]; P=0.0276), in the combined population (pemetrexed: n=390, docetaxel: n=392). Supplementary values were 101.3% (95% CLs: 57.9, 148.8), P=0.0186. For the secondary objectives, assessed in the population from the current study (pemetrexed: n=107, docetaxel: n=104), median OS was 11.7 and 12.2 months for the pemetrexed and docetaxel arms, respectively (HR [95% CLs]: 1.14 [0.78, 1.68], P=0.492). Supplementary values were 11.4 and 11.5 months, respectively (HR [95% CLs]: 1.02 [0.74, 1.40], P=0.926). Median PFS values were 2.8 and 3.1 months (HR [95% CLs]: 1.05 [0.75, 1.46], P=0.770) and ORR values were 9.6% and 4.1% (odds ratio [95% CLs]: 2.50 [0.76, 8.25], P=0.133) for pemetrexed and docetaxel, respectively. Pemetrexed-treated patients had significantly fewer drug-related grade 3-4 adverse events (pemetrexed: 20.8%, docetaxel: 40.2%; P=0.003). Few drug-related serious adverse events were reported (pemetrexed: 5 patients, docetaxel: 8 patients). CONCLUSION: The comparable efficacy and superior tolerability of pemetrexed compared with docetaxel in this study supports the use of single-agent, second-line pemetrexed for advanced non-squamous NSCLC in Chinese patients. ClinicalTrials.gov: NCT00391274.

PXR ligand classification model with SFED-weighted WHIM and CoMMA descriptors.

Understanding which type of endogenous and exogenous compounds serve as agonists for the nuclear pregnane X receptor (PXR) would be valuable for drug discovery and development, because PXR regulates a large number of genes related to xenobiotic metabolism. Although several models have been proposed to classify human PXR activators and non-activators, models with better predictability are necessary for practical purposes in drug discovery. Grid-weighted holistic invariant molecular (G-WHIM) and comparative molecular moment analysis (G-CoMMA) type 3D descriptors that contain information about the solvation free energy of target molecules were developed. With these descriptors, prediction models built using decision tree (DT)-, support vector machine (SVM)-, and Kohonen neural network (KNN)-based models exhibited better predictability than previously proposed models. Solvation free energy density-weighted G-WHIM and G-CoMMA descriptors reveal new insights into PXR ligand classification, and incorporation with machine learning methods (DT, SVM, KNN) exhibits promising results, especially SVM and KNN. SVM- and KNN-based models exhibit accuracy around 0.90, and DT-based models exhibit accuracy around 0.8 for both the training and test sets.

Epidermal growth factor receptor mutations in small cell lung cancer patients who received surgical resection in China.

To know the incidence of epidermal growth factor receptor (EGFR) mutations in small cell lung cancer (SCLC) patients who received surgical resection in mainland China. xTAG technology was used to detect the EGFR exon 19 and exon 21 mutations of 40 patients with SCLC who received surgical treatment in Zhejiang Cancer Hospital from 1998 to 2010. 2 of 40 cases were found with mutations in exon 19 of the EGFR gene. The mutation in exon 19 of the EGFR gene is in a female and non smoking patient which pathology is SCLC combined adenocarcinoma, and the other is male and smoking patient which pathology is SCLC combined squamous cell carcinoma. The EGFR mutation is rare in SCLC patients, and EGFR mutation might occur more often in combined SCLCs than conventional patients.

Asymmetrical reorientation of bimetallic core-shell nanowires.

The reorientation mechanism of core-shell nanowires is investigated and our theoretical studies reveal the significance of the structural configuration. In nanowires which have a larger lattice in the core region than in the shell, for example, Au-core and Pd-shell, the surface stress and interfacial stress may synergistically cause them to reorient spontaneously, but they can revert back to the original state upon an appropriate tensile loading. In contrast, the misfit interface is detrimental to spontaneous reorientation in nanowires which have a smaller lattice in the core than in the shell such as the Pd-core and Au-shell structure, but uniaxial tensile loading causes the nanowires to transform in another way. This asymmetrical reorientation is caused by the different intrinsic stress as well as distinctive slipping characteristics, namely partial slipping and perfect slipping in the compressive and tensile processes.

Self-reported frailty is associated with low calcaneal bone mineral density in a multiracial population of community-dwelling elderly.

INTRODUCTION: Low bone mineral density (BMD) is associated with frailty assessed using performance-based measures. However, the latter can be cumbersome and difficult to standardize. We examined whether an easily obtained self-reported frailty measure also predicted low BMD. METHODS: In 230 elderly (82% female, 58% African-American), calcaneal BMD was measured by DXA and frailty evaluated using the VES-13 questionnaire. In addition to the original scoring, we developed a modified scoring system which provided a broader assessment of frailty and excluded age, which is a known independent predictor of BMD. A telephone interview conducted 6 years later ascertained interval fragility fractures and survival status. RESULTS: A higher modified frailty score was associated with lower BMD (p = 0.002), even after adjusting for age, weight, sex, and race and was more predictive of death at 6 years (p = 0.009) than the original score (p = 0.08). Based on our model, a subject with the highest frailty score differed from an otherwise similar subject with the lowest score by a calcaneal BMD of 1.4 T-score units, corresponding to 2-3 times higher fracture risk. CONCLUSION: Self-reported frailty is associated with low calcaneal BMD and can be used to identify subjects with a greater risk of osteoporosis than expected from traditional risk factors.

Association of prostaglandin-endoperoxide synthase 2 gene polymorphisms with asthma and atopy in Chinese children.

BACKGROUND: Cyclooxygenase-2 (COX-2) plays essential roles in inflammation. Previous studies have suggested associations between prostaglandin-endoperoxide synthase 2 (PTGS2) polymorphisms and prostaglandins production in asthma. OBJECTIVE: We have investigated the effects of Chinese tagging single nucleotide polymorphisms (SNPs) of PTGS2 on asthma traits in 299 Chinese asthmatic children and 175 controls. METHODS: Plasma total and allergen-specific IgE were measured by enzyme immunoassay. PTGS2.8473T-->C in the 3'-untranslated region of exon 10 and three tag SNPs covering most of the variations in PTGS2 haplotypes in Chinese were genotyped by restriction fragment length polymorphism. RESULTS: Among the four SNPs, only PTGS2.8473 showed significant association with asthma (P = 0.034) and atopy (P = 0.005 when compared with non-atopic controls; P = 0.023 with all controls). Carriers of the C allele had a 1.5-fold (95% confidence interval: 1.01-2.30) risk of developing asthma than those homozygous for the T allele. Multivariate regression revealed significant correlations between PTGS2.8473 and forced expiratory volume in 1 s (FEV(1); P = 0.002) and peak expiratory flow rate (PEFR; P = 0.001) with age and gender adjusted. Patients with the C allele of PTGS2.8473 had significantly lower FEV(1) (median: 90.0%vs 98.0%; P = 0.0047) and PEFR (70.0%vs 73.5%; P = 0.0065) than those homozygous for the T allele. No significant association between plasma total and allergen-specific IgE and these SNPs or with their haplotypes was found. CONCLUSIONS: PTGS2.8473 polymorphism is associated with asthma, atopy and lung function but not plasma IgE in Chinese children. This may help to explore the pharmacogenetics of COX-2 inhibitors.

Apolipoprotein epsilon-4 allele and the two-year progression of cognitive function in Chinese subjects with late-onset Alzheimer's disease.

BACKGROUND: Although the significance of apolipoprotein E4 (Apo E4) in Alzheimer's disease (AD) has been well established in Caucasian populations, its role in determining the rate of cognitive decline in other ethnic groups has yet to be determined. This study examined the two-year progression of cognitive decline and its association with Apo E4 allelic status in a group of Chinese elderly subjects with AD. METHOD: One hundred and four Chinese subjects with mild and moderate AD as assessed by the Clinical Dementia Rating (CDR 1 and 2) were followed up at a mean (SD) duration of 22.53 (5.21) months. The rate of cognitive decline and its association with Apo E4 allelic status was evaluated RESULTS: At follow-up, 74 (73 percent) subjects were reassessed. Forty-nine remained stable at the same CDR and 25 had deteriorated. The mean (SD) deterioration in the Mini-Mental State Examination (MMSE) was 2.52 (4.38) and in the Mattis Dementia Rating Scale (DRS) was 9.03 (14.98) (paired t-test, p < 0. 001). There was no significant difference in the baseline MMSE and DRS scores between the "stable", "deteriorated", or "deceased" groups. Mildly demented subjects with the Apo E4 allele were more likely to have deteriorated to a more severe CDR than subjects without the Apo E4 allele (Pearson chi2 = 5.72, df 1, p = 0.017, Odds ratio = 6.3, CI 1.3 to 30.53). CONCLUSION: The presence of the Apo E4 allele may influence the rate of cognitive deterioration, particularly in subjects with mild AD.

Novel mutations in type 2 Gaucher disease in Chinese and their functional characterization by heterologous expression.

We investigated 10 unrelated Chinese patients with type 2 Gaucher disease and performed ex vivo expression for the novel mutations to characterize their functional defects. These patients were diagnosed by enzymatic assays and clinicopathologic features over the past five years in a national centre in China. Genomic DNA was sequenced by a two-stage PCR approach for mutations in the functional GBA gene. Novel mutations were expressed with baculovirus-transfected Sf21 cells. Six novel mutations were found (in traditional nomenclature): P122L, Y363C, N382K, L383R, L385P, and M416V. Review of reported mutations indicated clustering of type 2 mutations in three regions of the GBA gene. Expression of novel mutations revealed that the enzyme defect could arise from one of two mechanisms: loss of catalytic activity (Y363C and M416V) or enzyme instability (P122L and N382K).