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Purpose: To explore the clinical characteristics of pediatric pelvic fracturs caused by traffic accidents and to analyze the accompanying injuries and complications. Methods: A total of 222 cases involved traffic accidents was enrolled in this case-control study. The data of children with pelvic fractures caused by traffic accidents who were admitted to our hospital from January 2006 to December 2021 were analyzed retrospectively. Sex, age, Tile classification, abbreviated injury scale score, injury severity score, mortality, and accompanying injuries were studied. The ANOVA was used for measurement data, and the non-parametric rank sum test was used for non-normally distributed data. The Fisher's exact probability method was used for the count data. Results: Of all enrolled cases, 140 are boys and 82 are girls, including 144 cases aged < 6 years, 65 aged between 6 and 12 years, and 13 aged > 12 years. Depending on the injury mechanism, there are 15 cases involving pedestrians vs. motorcycles (PVM), 91 cases involving pedestrians vs. passenger cars (PVC), 78 cases involving pedestrians vs. commercial vehicles (PVV), and 38 cases involving motor vehicles vs. motor vehicles (MVM). Associated injuries are reported in 198 cases (89.2%), primarily involving the abdomen injury in 144 cases (64.9%), and lower limb injury in 99 cases (44.6%). PVV injury involves longer hospital stay (p = 0.004). Intensive care unit admission rate is significantly higher in the MVM group than in other groups (p = 0.004). Head injury (p = 0.001) and face injury (p = 0.037) are more common in the MVM group, whereas abdominal injury (p = 0.048) and lower limb injury (p = 0.037) are more common in the PVV group. In the MVM group, the brain injury (p = 0.004) and femoral neck injury (p = 0.044) are more common. In the PVM group, the mediastinum (p = 0.004), ear (p = 0.009), lumbar vertebrae (p = 0.008), and spinal cord (p = 0.011) are the most vulnerable regions, while in the PVV group, the perineum (p 12 years have higher pelvic abbreviated injury scale scores (p = 0.019). There are significant differences in the classification of pelvic fractures among children < 6, 6 – 12, and > 12 years of age, with Tile C being more likely to occur in children > 12 years of age (p = 0.033). Children aged > 12 years are more likely to sustain injuries to the spleen (p = 0.022), kidneys (p = 0.019), pancreas (p

The increasingly frequent and severe regional-scale compound heatwave‒drought extreme events (CHDEs), driven by global warming, present formidable challenges to ecosystems, residential livelihoods, and economic conditions. However, uncertainty persists regarding the future trend of CHDEs and their insights into regional spatiotemporal heterogeneity. By integrating daily meteorological data from observations in 1961–2022 and global climate models (GCMs) based on the Shared Socioeconomic Pathways, the evolution patterns of CHDEs were compared and examined among three sub-catchments of the Yangtze River Basin, and the return periods of CHDE in 2050s and 2100s were projected. The findings indicate that the climate during the 2022 CHDE period was the warmest and driest recorded in 1961–2022, with precipitation less than 154.5 mm and a mean daily maximum temperature 3.4 °C higher than the average of 1981–2010, whereas the characteristics in the sub-catchments exhibited temporal and spatial variation. In July–August 2022, the most notable feature of CHDE was its extremeness since 1961, with return periods of ∼200-year in upstream, 80-year in midstream, and 40-year in downstream, respectively. By 2050, the return periods witnessed 2022 CHDE would likely be reduced by one-third. Looking towards 2100, under the highest emission scenario of SSP585, it was projected to substantially increase the frequency of CHDEs, with return periods reduced to one-third in the upstream and downstream, as well as halved in the midstream. These findings provide valuable insights into the changing risks associated with forthcoming climate extremes, emphasizing the urgency of addressing these challenges in regional management and sustainable development.

IntroductionMale pattern baldness (MPB), also known as androgenetic alopecia, represents the most prevalent form of progressive hair loss in humans. It is characterized by a distinctive pattern of hair loss progression from the scalp; however, its underlying mechanism remains elusive and is influenced by hereditary, immune, and environmental factors. Genome-wide association studies (GWASs) have uncovered numerous risk genes/loci among European individuals with MPB. However, the validation of these susceptibility genes/loci within Han Chinese men remains largely unexplored. The aim of this study was to investigate whether the 71 susceptibility loci identified in a recent GWAS among European men also confer risk for MPB in Chinese men.MethodsForty-seven single nucleotide polymorphisms (SNPs) previously reported in GWASs of MPB were selected and genotyped in independent individuals comprising 499 Han Chinese cases and 1,489 controls using the Sequenom MassArray system. After stringent quality control measures, 25 SNPs were subjected to statistical analyses. Cochran–Armitage trend test was used to evaluate the association between SNPs and disease susceptibility. To address multiple tests, Bonferroni correction was conducted, setting the threshold for statistical significance at a p-value

The risk assessment of rockburst intensity is significant for tunnel construction safety. First, the depth of the rockburst (X1), the uniaxial compressive strength of the rocks (X2), the brittleness coefficient of the rocks (X3), the stress coefficients of the rocks (X4), and the elastic energy index (X5) are adopted as the evidence body, and their essential certainty and reliability is determined using the entropy-gray correlation theory. Second, the synthetic certainty reliability of other samples is calculated based on the evidence theory. Relatively to the traditional gray extension model, it can improve the predictive accuracy and determine the certainty and reliability of different evidence bodies. The difference of importance between other evidence bodies can be reflected; and an interval scale can be taken into consideration in the evaluation process, so the proposed theory can reasonably predict the grade criterion which is interval form. Conclusion demonstrated that the suggested approach is entirely consistent with the actual investigation. The proposed model not only considers the unreliability or reliability of the problem but also solves some degrees of uncertainty and ambiguity of the datum; it enhances the predictive efficiency and provides a new way and thought for future risk assessment of rockburst intensity.

The occurrence of debris flow hazards has significant destructive effects people’s safety and the safety of their property, so the risk assessment of debris flow hazards has great significance. The maximum amount of debris flow at one time (X1), the reserves of loose substance (X2), the watershed area (X3), the length of the ditch (X4), the relative height difference (X5), the gradient of side slope (X6), the longitudinal slope of main ditch (X7), the length ratio of replenishment section (X8), the daily maximum rainfall (X9), and Faults developed in the watershed (X10) are selected as the evaluation index at first. Then the gray system-variable fuzzy sets coupling model is introduced; secondly, the relative membership degree matrix about the fuzzy variable sets is established, and the weight coefficients considering the uncertainty of assessment indices are determined based on the entropy weight method; finally, the susceptibility level of debris flow hazards is determined using the mean ranking feature value. The conclusion is drawn that the results obtained based on the coupling technique are consistent with the current specification; its accuracy arrives at 83%, and the method is feasible for the susceptibility level assessment of debris flow hazards. Compared to the traditional variable fuzzy sets model, it avoids the uncertainty of magnitude in the standard analysis, it can ensure the objectivity and accuracy of the calculation result, and its calculation process is simple and efficient. In total, the findings of the proposed model provide an alternate way to assess the susceptibility level of debris flow hazards and improve the evaluation accuracy in the future.

The molecule of title compound, C33H28N2O4, comprises an indole unit (A), an isoquinoline moiety (B) and a benzene ring (C). The dihedral angles between these groups are A/B = 57.47 (1), A/C = 18.48 (1) and B/C = 57.97 (1) °. The ethyl acrylate group at the 2-position is nearly co-planar with the indole unit [3.81 (2)°], while that at the 7-position is distinctly non-coplanar [52.64 (1)°]. Intramolecular π–π interactions between the indole unit and benzene ring help to establish the clip-shaped conformation of the molecule. In the crystal, the molecules are assembled into two-dimensional layers via C—H...O hydrogen bonds, π–π and C—H...π interactions. Hirshfeld surface analysis illustrates that the greatest contributions are from H...H (63.2%), C...H/H...C (15.4%) and O...H/H...O (14.8%) contacts. The terminal C2H5 group of one of the ethyl acrylate side chains is disordered over two positions of equal occupancy.

Abstract. Background:. Single-nucleotide polymorphisms (SNPs)-associated genes and long non-coding RNAs (lncRNAs) can contribute to human disease. To comprehensively investigate the contribution of lncRNAs to breast cancer, we performed the first genome-wide lncRNA association study on Han Chinese women. Methods:. We designed an lncRNA array containing >800,000 SNPs, which was incorporated into a 96-array plate by Affymetrix (CapitalBio Technology, China). Subsequently, we performed a two-stage genome-wide lncRNA association study on Han Chinese women covering 11,942 individuals (5634 breast cancer patients and 6308 healthy controls). Additionally, in vitro gain or loss of function strategies were performed to clarify the function of a novel SNP-associated gene. Results:. We identified a novel breast cancer-associated susceptibility SNP, rs11066150 (Pmeta = 2.34 × 10−8), and a previously reported SNP, rs9397435 (Pmeta = 4.32 × 10−38), in Han Chinese women. rs11066150 is located in NONHSAT164009.1 (lncHSAT164), which is highly expressed in breast cancer tissues and cell lines. lncHSAT164 overexpression promoted colony formation, whereas lncHSAT164 knockdown promoted cell apoptosis and reduced colony formation by regulating the cell cycle. Conclusions:. Based on our lncRNA array, we identified a novel breast cancer-associated lncRNA and found that lncHSAT164 may contribute to breast cancer by regulating the cell cycle. These findings suggest a potential therapeutic target in breast cancer.

Katsuwonus pelamis peptide and its complexes have the effect of lowering uric acid (UA)-levels. To identify the effect and possible mechanisms, different concentrations of Katsuwonus pelamis peptide and its complexes were administered to the zebrafish and mice hyperuricemia models, and the UA level was measured. Meanwhile, the hyperuricemic mice were treated orally at 0.83, 1.67, and 5.00 mg/g body weight for 7 days with Katsuwonus pelamis peptide and the complexes groups, separately. The levels of serum UA (SUA), urinary UA (UUA), serum creatinine (SCR), blood urine nitrogen (BUN), and xanthine oxidase (XOD) activities were detected in each group. The results showed that the Katsuwonus pelamis peptide (125 μg/ml) and its complexes (83.3 and 250 μg/ml) effectively reduced UA level in zebrafish with hyperuricemia (p < 0.05). The Katsuwonus pelamis peptide at high concentration (5.00 mg/g) decreased the SUA level, SCR level, BUN level, and hepatic XOD activity, and the complexes (1.67 and 5.00 mg/g) significantly reduced the SUA level and hepatic XOD activity (p < 0.05) in the hyperuricemic mice. In addition, in a hyperuricemic mouse model, the UUA level was increased after treatment with Katsuwonus pelamis peptide and its complexes at high concentrations (p < 0.05). The total therapeutic effects in the Katsuwonus pelamis peptide complex group were better than those in the Katsuwonus pelamis peptide group. Thus, Katsuwonus pelamis peptide and its complexes may possibly be used to prevent hyperuricemia via promoting urate secretion and inhibiting XOD activity production.

Abstract Background The roots of Salvia miltiorrhiza are used in traditional Chinese medicine (TCM) and have high medicinal value. Tanshinone IIA (Tan IIA) is the active ingredient of Salvia miltiorrhiza which can inhibit the growth of acute leukemia cell lines in vitro, although the mechanism remains unclear. Methods CCK-8 assays and BrdU stain were used to evaluate cell proliferation ability. Western blot analysis was used to detect protein expression. miR-497-5p expression level was detected by using qRT-PCR, and Annexin V-FITC/propidium iodide (PI) was used to detect cell apoptosis. Results Here we reported that Tan IIA could inhibit cell proliferation, induce cell cycle arrest, and promote cell apoptosis in acute myeloid leukemia (AML) cells. Thus, Tan IIA had the anti-cancer activity in AML cell lines, which was likely mediated by up-regulation of miR-497-5p expression. Our data further showed that in AML cells, the same effects were observed with overexpression of miR-497-5p by a miR-497-5p mimic. We demonstrated that Tan IIA could inhibit the expression of AKT3 by up-regulating the expression of miR-497-5p. We subsequently identified that AKT3 was the direct target of miR-497-5p, and that treatment with Tan IIA obviously reversed the effect of treatment with an miR-497-5p inhibitor under harsh conditions. In turn, PCNA expression was increased and cleaved Caspase-3 was suppressed, which contributed to the growth of AML cells. Conclusions Our results showed that Tan IIA could inhibit cell proliferation in AML cells through miR-497-5p-mediated AKT3 downregulation pathway.

Abstract. Biologic drugs have been increasingly used in the treatment of psoriasis and are especially favorable for severe, recalcitrant, and special-type cases. Therefore, appropriate, effective, and safe use of biologic drugs has drawn attention from dermatologists. For this purpose, Chinese experts majoring in psoriasis analyzed domestic and international research data, summarized current clinical experiences, investigated features of Chinese patients with psoriasis, and finally formulated the present consensus, which provides detailed guidances to clinicians in terms of the principles and methods of the application of biologics, the efficacy and safety profile, patient screening and monitoring, main adverse events and corresponding solutions, and precautions for special patient populations.

Sea cucumbers are one of many marine echinoderm animals that contain valuable nutrients and medicinal compounds. The bioactive substances in sea cucumbers make them have promising biological and pharmacological properties, including antioxidant, anti-bacterial, and anti-tumor effects. In this study, sea cucumber intestinal peptide (SCIP) is a small molecular oligopeptide (

Abstract. The SARS-CoV-2 infection has brought a great challenge in prevention and control of the national epidemic of coronavirus disease 2019 (COVID-19) in China. During the COVID-19 epidemic, properly carrying out pre-examination and triage for patients with skin lesions and fever has become a practical problem encountered in hospitals for skin diseases and dermatology clinics in general hospitals. Some of the carriers of the SARS-CoV-2 and patients with COVID-19 in the early stage may not present with any symptoms of COVID-19, while certain other skin diseases can also cause fever. Therefore, to properly deal with the patients presenting at dermatology clinics, the Chinese Society of Dermatology organized experts to formulate principles and procedures for the pre-examination and triage of patients at dermatology clinics during the COVID-19 epidemic.

Abstract. Background:. Spider nevi (SN) are quite common in children. SN are treated via different techniques, and complete removal often requires multiple treatments. However, few studies have evaluated the treatment of SN. The present study aimed to evaluate the therapeutic effect and safety of a 595-nm pulsed-dye laser (PDL) for treating facial SN in children. Methods:. A total of 110 children aged 0.2 to 12 years with facial SN were treated with a 595-nm PDL in a single institution from January 2016 to February 2018. In accordance with the treatment method, the patients were retrospectively divided into the small-spot-combined-with-large-spot group (SL-group) and the large-spot group (L-group). Patients with poor therapeutic results were re-treated every 6 weeks until the lesions disappeared. The minimum follow-up period was 1 year. The groups were compared using independent-samples t tests, Mann-Whitney U test, Chi-square test, and Fisher exact probability test. Results:. The therapeutic efficacy was significantly higher in the SL-group than in the L-group, with clearance rates of 90.9% and 53.0% after the primary treatment, respectively (χ2 = 17.937, P

Spatial self-phase modulation (SSPM) as a purely coherent non-linear optical effect (also known as Kerr effect) can support strong broadband phase modulation, which is essential for all-optical applications. Besides this, the increasing use of two-dimensional (2D) materials opens up new prospects in this field of research. In this work, we report a broadband SSPM response from 2D transition metal carbonitrides (MXenes) and Nb2C, arising in the near-infrared (1,550 nm) range. Based on the SSPM measurements of few-layer Nb2C nanosheets, the third-order non-linear optical parameters of Nb2C, including the non-linear refractive index n2 and susceptibility χ(3), were determined at 400, 800, 1,300, and 1,550 nm. Moreover, the physics mechanism of the dynamic formation process of SSPM diffraction rings was exploited. The formation time of SSPM diffraction rings can be divided into two typical parts which correspond to the polarization and reorientation of 2D Nb2C nanosheets. As a proof of concept, we demonstrate the nonreciprocal light propagation at wavelengths of 1,300 and 1,550 nm by constructing an Nb2C/water hybrid structure. Our results reveal strong optical phase modulation of Nb2C in the infrared region, thus showing the great potential of MXene materials for use in passive photonic devices.

Objective. To investigate the effects of mung bean peptide and its’ complexes on promoting lead excretion and neuroprotection of zebrafish. Methods. The lead poisoning models of zebrafish were established by lead acetate solution; the models were treated with high and low concentrations (58.3 and 175 μg/mL) of mung bean peptides, with high, medium, and low concentrations (27.8, 83.3, and 250 μg/mL) of mung bean peptide complexes, separately. The effects of the mung bean peptide complexes on the lead content, axonal fluorescence intensity, and peripheral motor nerve length changes were identified in the zebrafish model, and the effects of mung bean peptide and its’ complexes on zebrafish's lead excretion, axonal protection rate, and peripheral movement promotion rate of nerve regeneration were calculated. Results. The effects of high concentration of mung bean peptide (175 μg/mL) in promoting lead excretion was 29% (p0.05) and 42% (p

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, and it has no effective treatment. We previously reported that the native polypeptide vglycin (purified from soybean) has a beneficial role in regulating glucose homeostasis in diabetic rats. In this study, we investigated the preventive effects of vglycin and possible mechanisms of action in hepatic steatosis using a high-fat diet (HFD)-induced mouse model. The results revealed that vglycin decreased the body weight, liver weight, Lee’s index, and plasma triglyceride level in HFD-fed C57BL/6J mice. Furthermore, it prevented liver injury, inflammation and insulin resistance by inhibiting fat accumulation in liver. These beneficial effects of vglycin are probably attributable to the activation of the AMP-activated protein kinase (AMPK) pathway and the down-regulation of fatty acid synthase (FAS). Therefore, vglycin holds promise as an oral drug for the prevention of NAFLD.

Intervertebral disk degeneration (IDD) is characterized by changes in the nucleus pulposus (NP) extra cellular matrix that compromise disk structural integrity. In a miRNA screen of human IDD patient NP tissue, the authors identify deregulated miR-141 and show that direct injection of nanoparticle-coupled miR-141 into the NP alleviates IDD in mice.

Abstract Background Little data are available regarding the effects of pedicle screws on the intervertebral disc stress for different spinal segments. The aim of this study was to analyze the intervertebral disc stress in response to the placement of pedicle screws. Methods T3–4, T11–12, T15–L1, L3–4, and L4–5 intervertebral disc segments from six porcine spine specimens were harvested. A compressive load of 200 N was applied both before and after the pedicle screw was implanted on the left side of each target segment; the resulting pressure was measured during vertical, 5° anterior flexion, 5° posterior extension, and 5° lateral bending. Results The posterior intradiscal pressures of the intervertebral disc were significantly lower in the fixed group than in the unfixed group for all segments during vertical, 5° anterior flexion, and 5° posterior extension. The left pressures of the intervertebral disc were significantly lower in the fixation group for all segments. During 5° lateral bending, the left intervertebral disc pressures were significantly lower in the fixation group. Lower mean pressures were observed in the fixed group. Conclusions Unilateral pedicle screws can effectively reduce the pressure of the fixed lateral intervertebral disc. Moreover, it can change the pressure distribution of the intervertebral disc and reduce the pressure of the entire intervertebral disc, especially the posterior side of the intervertebral disc.

Abstract Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a nuclear receptor demonstrated to play an important role in various biological processes. The aim of this study was to determine the effect of PPARγ on liver regeneration upon partial hepatectomy (PH) in mice. Mice were subjected to two-thirds PH. Before surgery, mice were either treated with the PPARγ agonist rosiglitazone, the PPARγ antagonist GW9662 alone, or with the c-met inhibitor SGX523. Liver-to-body-weight ratio, lab values, and proliferation markers were assessed. Components of the PPARγ-specific signaling pathway were identified by western blot and qRT-PCR. Our results show that liver regeneration is being inhibited by rosiglitazone and accelerated by GW9662. Inhibition of c-Met by SGX523 treatment abrogates GW9662-induced liver regeneration and hepatocyte proliferation. Hepatocyte growth factor (HGF) protein levels were significantly downregulated after rosiglitazone treatment. Activation of HGF/c-Met pathways by phosphorylation of c-Met and ERK1/2 were inhibited in rosiglitazone-treated mice. In turn, blocking phosphorylation of c-Met significantly abrogated the augmented effect of GW9662 on liver regeneration. Our data support the concept that PPARγ abrogates liver growth and hepatocellular proliferation by inhibition of the HGF/c-Met/ERK1/2 pathways. These pathways may represent potential targets in response to liver disease and could impact on the development of molecular therapies.

Objective To evaluate the damage of white matter fiber tracts in the center and periphery of infarcts in the model rats of ischemic stroke. Methods A total of 25 Sprague-Dawley (SD) rats were randomly divided into control group (N = 10) and middle cerebral artery occlusion (MCAO) group (N = 15). MCAO model was established by occluding with suture. At 3 h, 6 h, 1 d, 2 d, 3 d, 4 d and 7 d after model establishment, perform diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) at high-field 7.0T MRI, choose cortex, subcortex and corpus callosum of infarct side as regions of interest (ROIs) and calculate the values of fractional anisotropy (FA), mean diffusion coefficient (MD), radial diffusivity (λ║) and axial diffusivity (λ┴), choose internal capsule as ROI and calculate number of tracts (NT). Results At different time points, FA value (P = 0.000, for all), MD value (P = 0.000, for all), λ║ value (P = 0.000, for all) and λ┴ value (P = 0.000, for all) in the cortex, subcortex and corpus callosum ofinfarct side had significant difference between 2 groups. As time extended, in MCAO group FA value in cortex, subcortex and corpus callosum of infarct side was slowly increased in superacute phase (≤ 6 h; P = 0.000, for all), obviously decreased in acute phase (6 h to 3 d; P= 0.000, for all) and kept stable in subacute phase (3 d to 8 weeks). MD value, λ║ value and λ┴ value were obviously increased in acute phase (P = 0.000, for all) and kept stable in subacute phase. FA value in cortex, subcortex and corpus callosum of infarct side (P = 0.003, 0.000, 0.000), MD value in subcortex (P = 0.013), λ║ (P = 0.012, 0.001) and λ┴ (P = 0.001, 0.036) values in subcortex and corpus callosum had significant differences between 2 groups. At different time points, NT value of infarct side had significant difference between 2 groups (P = 0.000). As time extended, NT value of infarct side in MCAO group was slowly decreased in superacute phase (P = 0.032), obviously decreased in acute phase (P = 0.000, for all) and kept stable in subacute phase. Compared to control group, NT value of infarct side in MCAO group was significantly lower at each time point (P = 0.000). DTT showed the white matter fiber tracts of infarct side in MCAO group were twisted and fractured. The damaged fibers tended to be around the edge of the lesion 1 d after MCAO model establishment. Conclusions At the superacute phase to acute phase after ischemic stroke, nerve damage persisted until neural remodeling appeared in the subacute phase. DTT observed the damaged fibers tended to be around the edge of the lesion, suggesting the protective effect of damaged fibers surrounding the lesion. DOI: 10.3969/j.issn.1672-6731.2018.01.008

Abstract Background The therapeutic efficacy of serial casting on idiopathic scoliosis has been gradually documented. However, literatures on serial casting for congenital scoliosis (CS) remain extremely rare. This paper aimed to compare the treatment outcomes of serial casting between CS and non-CS patients to comprehensively evaluate the therapeutic characteristics of serial casting on CS patients. Methods A total of 23 early-onset scoliosis cases were included and divided into congenital scoliosis (CS, n = 8) and non-congenital group (non-CS, n = 15). Therapeutic outcomes including the major curve Cobb angle, thoracic kyphosis angle, lumbar lodosis angle, and thoracic spine growing rate were compared between groups at precast, after the first cast, and at the latest follow-up, respectively. Results All patients received the first cast at the age of 3.25 ± 1.20 years and 5.70 ± 1.18 times of cast corrections. The average casting time was 17.17 ± 3.38 months, and the mean follow-up time was 23.91 ± 12.28 months. Both CS and non-CS groups had significant decrease in Cobb angle after the first cast and at the latest follow-up (all P

The persistence infection of low-risk type (type 6 or type 11) of human papillomavirus (HPV) is the main cause of genital warts. Given the high rate of recurrence after treatment, the use of a new molecular agent is certain to be of value. The aim of this study was to achieve targeted inactivation of viral E 7 gene in keratinocytes using the reprogrammed clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system. To accomplish this, a universal CRISPR-Cas9 system for targeting both HPV6/11 E 7 genes was constructed by using a dual guide RNA vector. After transfection of the vector into E 7-transfromed keratinocytes, the expression level of E 7 protein was measured using western-blot analysis and the sequence of the E 7 gene was determined using Sanger sequencing. Cell proliferation was analyzed by CCK-8 assay, and cell apoptosis was evaluated by Hoechst 33258 staining, flow cytometry analysis and ELISA assay. The results indicated that both HPV6/11 E 7 genes can be inactivated by the single CRISPR-Cas9 system. Furthermore, silencing of E 7 led to inhibition of cell proliferation and induction of apoptosis in E 7-transfromed keratinocytes but not in normal keratinocytes. Our data suggested that the reprogrammed CRISPR-Cas9 system has the potential for the development of an adjuvant therapy for genital warts.

Bioactive metabolites in Codonopsis pilosula are of particular interest as an immunostimulant. Methyl jasmonate (MeJA) plays an important role in the elicitation of metabolite biosynthesis. Here, we explored the response of metabolites to MeJA elicitation in C. pilosula adventitious roots and multiple shoots. The results showed that the biomass, polysaccharide, and lobetyolin content of adventitious roots exhibited the highest increases with 100 µmol·L−1 MeJA at the 16th day of subculture, whereas the atractylenolide III (a terpenoid) content increased extremely with 50 µmol·L−1 MeJA treatment at the 7th day of subculture. In addition, the biomass and lobetyolin content significantly increased at the 4th day after treatment. Similarly, the polysaccharide and lobetyolin content increased in multiple shoots. Further identification of different metabolites responding to MeJA by 1H-NMR showed an extremely significant increase of the lobetyolinin level, which coincided with lobetyolin. Accordingly, the precursor, fatty acids, showed a highly significant decrease in their levels. Furthermore, a significant increase in β-d-fructose-butanol glycoside was detected, which was accompanied by a decrease in the sucrose level. Accordingly, the enzyme genes responsible for terpenoid and carbohydrate biosynthesis, CpUGPase, and CpPMK, were up regulated. In conclusion, MeJA promoted culture growth and accelerated bioactive metabolite accumulation by regulating the expression of the metabolite biosynthesis related genes, CpUGPase and CpPMK in C. pilosula.

BACKGROUND:Liver X receptor alpha (LXRα) and endoglin have been postulated to play roles in trophoblast invasion and lipid metabolic disturbances. However, the relationship between LXRα and endoglin levels in serum and placenta of patients with preeclampsia remains poorly understood. The objective of this study was to identify correlations between LXRα, endoglin and preeclampsia and provide new feasible methods of clinical prediction and treatment for preeclampsia. METHODS:We enrolled 45 patients with preeclampsia (24 with moderate preeclampsia and 21 with severe preeclampsia) and 15 normal pregnant women (control group) who were admitted to the Department of Obstetrics of the General Hospital of Beijing Command between October 2012 and July 2013 in this study. Serum and placental LXRα and endoglin levels were analyzed by enzyme-linked immunosorbent assay, real-time quantitative PCR, tissue microarray and immunohistochemistry. RESULTS:Serum and placental LXRα and endoglin levels were significantly higher in patients with preeclampsia than those in control group (P

AIM: To screen diabetic retinopathy(DR)in diabetes mellitus(DM)patients by non-mydriatic fundus photography, and to investigate the risk factors in DM patients for DR.METHODS:A total of 768 patients with DM type 2 treated in the department of endocrinology in our hospital from November 2010 to December 2011 were enrolled in this study. All patients underwent non-mydriatic fundus photography, and were divided into two groups: non-diabetic retinopathy group(NDR group)and DR group, in accordance with the international clinical staging standard of DR released in 2002. Weight, height, blood pressure and medical history were recorded. Serum levels of fasting plasma glucose(FPG), lipids, glycated hemoglobin(HbA1c)and uric acid(UA)were measured.RESULTS: Totally 317 out of 768 DM patients(41.3%)were diagnosed with DR. The detection rate in women was significantly higher than that in men(45.2% vs 37.6%, PPCONCLUSION:DR in DM patients is quite common and closely associated with duration, gender, blood pressure and glucose. Non-mydriatic fundus photography is a quite useful method for screening DR.

Atopic diseases, such as atopic dermatitis (AD) and asthma, are closely related to clinical phenotypes with hypersensitivity, and often share some similar genetic and pathogenic bases. Our recent GWAS identified three susceptibility gene/loci FLG (rs11204971 and rs3126085), 5q22.1 (rs10067777, rs7701890, rs13360927 and rs13361382) and 20q13.33 (rs6010620) to AD. The effect of these AD associated polymorphisms in asthma is so far unknown. To investigate whether AD relevant genetic variants is identical to asthma and reveal the differences in genetic factors between AD and asthma in Chinese Han population, seven AD associated single nucleotide polymorphisms (SNPs) as well as 3 other SNPs (rs7936562 and rs7124842 at 11q13.5 and rs4982958 at 14q11.2) from our previous AD GWAS were genotyped in 463 asthma patients and 985 controls using Sequenom MassArray system. We found rs4982958 at 14q11.2 was significantly associated with asthma (P = 3.04×10(-4), OR = 0.73). We also detected one significant risk haplotype GGGA from the 4 SNPs (rs10067777, rs7701890, rs13360927 and rs13361382) at 5q22.1 in AD cases (P(correction) = 3.60×10(-10), OR = 1.26), and the haplotype was suggestive of risk in asthma cases in this study (P = 0.014, P(correction) = 0.084, OR = 1.38). These SNPs (rs11204971, rs3126085, rs7936562, rs712484 and rs6010620) at AD susceptibility genes/loci FLG, 11q13.5 and 20q13.33 were not associated with asthma in this study. Our results further comfirmed that 14q11.2 was an important candidate locus for asthma and demonstrated that 5q22.1 might be shared by AD and asthma in Chinese Han population.

Psoriasis is a common inflammatory skin disease with genetic components of both immune system and the epidermis. PSOR1 locus (6q21) has been strongly associated with psoriasis; however, it is difficult to identify additional independent association due to strong linkage disequilibrium in the MHC region. We performed stepwise regression analyses of more than 3,000 SNPs in the MHC region genotyped using Human 610-Quad (Illumina) in 1,139 cases with psoriasis and 1,132 controls of Han Chinese population to search for additional independent association. With four regression models obtained, two SNPs rs9468925 in HLA-C/HLA-B and rs2858881 in HLA-DQA2 were repeatedly selected in all models, suggesting that multiple loci outside PSOR1 locus were associated with psoriasis. More importantly we find that rs9468925 in HLA-C/HLA-B is associated with both psoriasis and vitiligo, providing first important evidence that two major skin diseases share a common genetic locus in the MHC, and a basis for elucidating the molecular mechanism of skin disorders.

Psoriasis is a common inflammatory skin disease characterized by thickened scaly red plaques. Previously we have performed a genome-wide association study (GWAS) on psoriasis with 1,359 cases and 1,400 controls, which were genotyped for 447,249 SNPs. The most significant finding was for SNP rs12191877, which is in tight linkage disequilibrium with HLA-Cw*0602, the consensus risk allele for psoriasis. However, it is not known whether there are other psoriasis loci within the MHC in addition to HLA-C. In the present study, we searched for additional susceptibility loci within the human leukocyte antigen (HLA) region through in-depth analyses of the GWAS data; then, we followed up our findings in an independent Han Chinese 1,139 psoriasis cases and 1,132 controls. Using the phased CEPH dataset as a reference, we imputed the HLA-Cw*0602 in all samples with high accuracy. The association of the imputed HLA-Cw*0602 dosage with disease was much stronger than that of the most significantly associated SNP, rs12191877. Adjusting for HLA-Cw*0602, there were two remaining association signals: one demonstrated by rs2073048 (p = 2 x 10(-6), OR = 0.66), located within c6orf10, a potential downstream effecter of TNF-alpha, and one indicated by rs13437088 (p = 9 x 10(-6), OR = 1.3), located 30 kb centromeric of HLA-B and 16 kb telomeric of MICA. When HLA-Cw*0602, rs2073048, and rs13437088 were all included in a logistic regression model, each of them was significantly associated with disease (p = 3 x 10(-47), 6 x 10(-8), and 3 x 10(-7), respectively). Both putative loci were also significantly associated in the Han Chinese samples after controlling for the imputed HLA-Cw*0602. A detailed analysis of HLA-B in both populations demonstrated that HLA-B*57 was associated with an increased risk of psoriasis and HLA-B*40 a decreased risk, independently of HLA-Cw*0602 and the C6orf10 locus, suggesting the potential pathogenic involvement of HLA-B. These results demonstrate that there are at least two additional loci within the MHC conferring risk of psoriasis.

PSORS1 (psoriasis susceptibility gene 1) is a major susceptibility locus for psoriasis. Several fine-mapping studies have highlighted a 300-kb candidate region of PSORS1 where multiple biologically plausible candidate genes were suggested. The most recent study has indicated HLA-Cw6 as the primary PSORS1 risk allele within the candidate region in a Caucasian population. In this study, a family-based association analysis of the PSORS1 locus was performed by analyzing 10 polymorphic microsatellite markers from the PSORS1 region as well as HLA-B, HLA-C and CDSN loci in 163 Chinese families of psoriasis. Five marker loci show strong evidence (P

Acetylcholinesterase (AChE; EC3.1.1.7) is well known for its role in the hydrolysis of acetylcholine at cholinergic synapses to terminate neurotransmission. In addition to its synaptic presence, AChE has been found to be in non-cholinergic cells such as hematopoietic and osteogenic cells. We have recently reported that AChE is expressed in various cells undergoing apoptosis. To characterize AChE in apoptotic cells and to investigate the role of AChE expression in apoptosis, we devised a method to purify AChE expressed in apoptotic human lung fibroblast cell line HLF. The isolation of this enzyme is mainly based on inhibitor ligand affinity chromatography using immobilized tacrine. However, this method is only effective in isolating active AChE. Here we employed antibody-based chromatography and found that both active and inactive AChE were present in apoptotic HLF cells. Active AChE was predominantly observed in the nuclei of apoptotic cells, while inactive AChE was mainly present in the cytoplasm. Therefore, our method provides an opportunity to investigate further the role of AChE, especially inactive AChE, in apoptosis.