Clinical, imaging, and pathological characteristics of congenital infiltrating lipomatosis of the face.

Congenital infiltrating lipomatosis of the face (CILF) is a rare congenital disease of the head and neck region. In this study, the cases of 20 patients diagnosed with CILF were reviewed retrospectively to analyse the characteristics of the disease. The symptoms, signs, and clinical progression were investigated. Radiological changes were analysed according to the distribution of the trigeminal nerve. The pathological features of the fatty facial lesions, jaw hyperplasia, and lingual lesions were further identified. All 20 patients demonstrated hemifacial hypertrophy at birth. None had a family history of the disease. Significant radiological features of CILF (prevalence ≥90%) included thickened buccal subcutaneous fat, palatal submucosal fat, and temporal subcutaneous fat, maxillary tuberosity heteroplasia, and fatty infiltration of the masseteric intermuscular space. With regard to the trigeminal nerve, the frontal branch region (CNV1) was rarely affected, while the maxillary (CNV2) and mandibular (CNV3) branch regions showed considerable changes. Pathologically, CILF was observed to be characterized by the infiltration of mature adipose tissue into the adjacent buccal soft tissue, osteal remodelling surrounded by sheets of mature lipocytes and supporting fibrovascular stroma, and lingual hamartoma. In summary, CILF exhibits distinct characteristics that are related to the regions controlled by the maxillary and mandibular branches of the trigeminal nerve, suggesting that CILF may be associated with early neural development.

miRNA-30a-5p-mediated silencing of Beta2/NeuroD expression is an important initial event of glucotoxicity-induced beta cell dysfunction in rodent models.

AIMS/HYPOTHESIS: The loss of beta cell function is a critical factor in the development of type 2 diabetes. Glucotoxicity plays a major role in the progressive deterioration of beta cell function and development of type 2 diabetes mellitus. Here we demonstrate that microRNA (miR)-30a-5p is a key player in early-stage glucotoxicity-induced beta cell dysfunction. METHODS: We performed northern blots, RT-PCR and western blots in glucotoxicity-exposed primary rat islets and INS-1 cells. We also measured glucose-stimulated insulin secretion and insulin content. In vivo approaches were used to evaluate the role of miR-30a-5p in beta cell dysfunction. RESULTS: miR-30a-5p expression was increased in beta cells after exposure to glucotoxic conditions, and exogenous miR-30a-5p overexpression also induced beta cell dysfunction in vitro. miR-30a-5p directly suppressed expression of Beta2/NeuroD (also known as Neurod1) by binding to a specific binding site in its 3'-untranslated region. After restoration of Beta2/NeuroD expression by knockdown miR-30a-5p or transfection of the Beta2/NeuroD gene, beta cell dysfunction, including decreased insulin content, gene expression and glucose-stimulated insulin secretion, recovered. Glucose tolerance and beta cell dysfunction improved on direct injection of Ad-si30a-5p into the pancreas of diabetic mice. CONCLUSIONS/INTERPRETATION: Our data demonstrate that miR-30a-5p-mediated direct suppression of Beta2/NeuroD gene expression is an important initiation step of glucotoxicity-induced beta cell dysfunction.

[Characteristic and prognosis of patients with non-EBV infection-associated hemophagocytic lymphohistiocytosis].

Objective: To explore the clinical characteristics and outcomes of patients with non-Epstein-Barr virus (EBV) infection-associated hemophagocytic lymphohistiocytosis (IAHLH) . Methods: Clinical data of 48 patients diagnosed with non-EBV IAHLH in Beijing Friendship Hospital from January 2015 to March 2021 were collected, and the clinical characteristics, treatment, curative effect and prognosis of the patients were analyzed retrospectively. Results: This study included 48 patients, 28 males and 20 females, with a median (range) age of 34.5 (2-74) years. Pathogens that cause IAHLH were as follows: virus (16 cases, 33.3%) , bacteria (17 cases, 35.4%) , parasitic agents (13 cases, 27.1%) , and fungi (2 cases, 4.2%) . The median time from onset to diagnosis of hemophagocytic syndrome (HLH) was 40 (10-160) days. The median (range) time duration from prodrome to the definite diagnosis of IAHLH was 67 (23-270) days. The clinical characteristics were fever (48 cases, 100%) , splenomegaly (34 cases, 70.8%) , cytopenia (38 cases, 79.1%) , elevated ferritin (45 cases, 93.8%) , elevated fasting triglyceride levels (7 cases, 14.6%) , hypofibrinogenemia (17 cases, 35.4%) , decrease natural killer cell activity (26 in 44 cases, 59.1%) , and elevated sCD25 (35 cases, 74.5%) . Twenty-five patients (52.1%) had adenopathy. Once a certain pathogen was identified as the causative factor of hemophagocytic lymphohistiocytosis (HLH) , cytotoxic agents and glucocorticoids were withdrawn, and specific pathogen-directed treatment was initiated. After treatment, 36 cases (75.0%) achieved complete response, and 14 of 15 patients (93.3%) with parasitic and fungal HLH got a response; however, the response rate of patient with bacterial and viral HLH was only 66.7% (22 of 33 patients) . The estimated 5-year overall survival rate was 72.3% (95%CI 50.3%-69.8%) . The adverse prognostic factors were total bilirubin over the upper limit of normal (OR=20.0, 95%CI 1.1-378.3, P=0.046) and pathogenic infection not fully controlled (OR=19.9, 95%CI 2.9-134.5, P=0.002) . Conclusion: Non-EBV IAHLH has a good prognosis. When diagnosed, cytotoxic agents and glucocorticoids should be tapered off, and pathogen-targeted therapy should be critically administered to clear the triggering infection.

[Clinical application of thoracodorsal artery perforator flaps in the repair of head and neck defects].

Objective: To analyse the clinical application of thoracodorsal artery perforator flaps (TDAPF) in the repair of head and neck defects. Methods: A retrospective review was conducted on 38 patients with oral and maxillofacial head and neck malignant tumors who underwent radical resection of oral and oropharyngeal carcinoma and TDAPF repair in the Department of Oral and Maxillofacial Head and Neck Oncology of the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from June 2017 to November 2018. Among them, 32 were males and 6 were females, aged 30-74 years. Flap size, vessel pedicle length, diameter and number of perforators, and flap fat thickness were recorded and counted. Elasti Meter and Skin Fibro Meter were applied to measure the skin elasticity and hardness in the donor areas of 4 kinds of skin flaps before the flap preparation. SPSS 19.0 statistical software was used for statistical analysis of the data. Results: All the flaps survived (100%). The mean elasticity of TDAPF [(41.2±12.9) N/m] was significantly lower than that of anterolateral thigh [(77.6±23.3) N/m, χ²=88.89, P<0.05], anterolateral thigh [(62.6±17.7) N/m, χ²=59.99, P<0.05] and or forearm flap [(51.7±8.6) N/m, χ²=37.82, P<0.05]. The hardness of TDAPF [(0.037±0.016) N] was also significantly lower than that of anterolateral femoral [(0.088±0.019) N, F=93.27, P<0.05], anteromedial femoral [(0.059±0.020) N, F=25.71, P<0.05] or forearm flap [(0.062±0.016) N, F=29.11, P<0.05]. Follow-up period ranged from 2 to 14 months. The 38 patients treated with TDAPF had a good recovery of the functions in the recipient areas, and the scars of the donor areas were not obvious after surgery, without serious complications. Conclusion: TDAPF is suitable for reconstruction of head and neck defect, with ductile texture and good recovery of the morphology and function of head and neck.

[Surface morphology and surface properties of Ti and TiZr implant materials].

Objective: To investigate the effects of hydrophilic treatment on the surface morphology and surface properties of pure titanium and titanium-zirconium alloy implants, and to provide reference for the studies of implant surface modification. Methods: The pure titanium group, the hydrophilic pure titanium group, the titanium zirconium alloy group and the hydrophilic titanium-zirconium alloy group were prepared by sandblasting and acid-etching or hydrophilic sandblasting and acid-etching, (11 specimens in each group). The surface morphology and surface properties of four types of titanium specimens were analyzed by surface contact angle meter, scanning electron microscope (SEM), optical profilometer, atomic force microscope (AFM) and Raman spectrometer. Results: The surface contact angles of hydrophilic pure titanium and hydrophilic titanium-zirconium alloy were 1.6°±0.3° and 1.5°±0.2°, and the surface contact angles of pure titanium and titanium-zirconium alloy were 101.4°±4.6° and 96.2°±3.0°, respectively. SEM showed that the nano-protrusions on the surface of pure titanium and titanium-zirconium alloys were less or even absent, while the nano-protrusions on the surface of hydrophilic pure titanium and hydrophilic titanium-zirconium alloys were relatively more; the nano-protrusions on the surface of hydrophilic pure titanium surface were small and dense relatively, but the nano-protrusions of the hydrophilic titanium-zirconium alloy had large diameters and were dispersed relatively. The optical profiler and AFM showed that the surface roughness of hydrophilic pure titanium and hydrophilic titanium-zirconium alloy was significantly higher than that of pure titanium and titanium-zirconium alloy (P<0.05). Raman spectroscopy showed that only the amorphous TiO(2) was present on the surface of the pure titanium group, while the rutile TiO(2) characteristic peak was observed in the other three groups, but the lateral inhomogeneity was observed. After Raman shift 610 cm(-1), the Raman spectra of four groups were similar. Conclusions: Hydrophilic sandblasting and acid-etching treatment can improve the surface hydrophilicity and surface roughness of pure titanium and titanium zirconium alloy, and improve the surface properties of pure titanium and titanium zirconium alloy implants.

[Genomic diversity and population structure of Helicobacter pylori isolates in China].

Objective: To learn about the overall genomic characteristics and population structure of Helicobacter pylori isolated in China. Methods: In this study, we used 10 public available genome sequences of H. pylori strains isolated in China, combined with other H. pylori sequences from GenBank, to analyzed the overall genomic characteristics of H. pylori isolated in China. Core genes and strain specific genes were determined for a further function definition. Results: A total of 1 203 core genes were found among all sequenced China H. pylori isolates. The number of strain specific genes ranged from 19 to 32. These genes mainly encodes hypothetical proteins which might play an important role in adaption to different hosts. Genomic variation regions were mainly in genes encoding type four secretion systems and restriction modification systems. All the China isolates belong to hpEastAsia group, hspEAsia subgroup. Prophages sequences were found in three China H. pylori strains, carrying key elements required for phage assembly. Conclusion: China H. pylori isolates belong to hpEastAsia group, hspEAsia subgroup, and some isolates contain prophages.

Similarities in sunlight-induced mutational spectra of CpG-methylated transgenes and the p53 gene in skin cancer point to an important role of 5-methylcytosine residues in solar UV mutagenesis.

In the p53 gene of human sunlight-associated skin cancers, 35 % of the mutations involve trinucleotide sequences with the rare base 5-methylcytosine (5'PymCG). In order to determine the involvement of 5-methylcytosine in sunlight-induced mutations, we have analyzed the cII transgene in mouse cells, a mutational target gene that we found is methylated at most CpG sequences. We report that the mutational spectra produced by irradiation with 254 nm UVC radiation and simulated sunlight, respectively, differ most dramatically by the much higher involvement of dipyrimidine structures containing 5-methylcytosine in the solar UV mutation spectrum (32 % versus 9 % of all mutations). A distinct mutational hotspot induced by simulated sunlight occurs at a sequence 5'TmCG and is associated with high levels of cis-syn cyclobutane pyrimidine dimer formation. A comparison of sunlight-induced mutational spectra of the cII and lacI transgenes, as well as the p53 gene in skin tumors, shows that 5-methylcytosine is involved in 25 to 40 % of all mutations in all three systems. The combined data make a strong case that cyclobutane pyrimidine dimers forming preferentially at dipyrimidine sequences with 5-methylcytosine are responsible for a considerable fraction of the mutations induced by sunlight in mammalian cells.

Involvement of 5-methylcytosine in sunlight-induced mutagenesis.

In human skin cancers, more than 30 % of all mutations in the p53 gene are transitions at dipyrimidines within the sequence context CpG, i.e. 5'-TCG and 5'-CCG, found at several mutational hotspots. Since CpGs are methylated along the p53 gene, these mutations may be derived from solar UV-induced pyrimidine dimers forming at sequences that contain 5-methylcytosine. In Xorder to define the contribution of 5-methylcytosine to sunlight-induced mutations, we have used mouse fibroblasts containing the CpG-methylated lacI transgene as a mutational target. We sequenced 182 UVC (254 nm UV)-induced mutations and 170 mutations induced by a solar UV simulator, along with 75 mutations in untreated cells. Only a few of the mutations in untreated cells were transitions at dipyrimidines, but more than 95% of the UVC and solar irradiation-induced mutations were targeted to dipyrimidine sites, the majority being transitions. After UVC irradiation, 6% of the base substitutions were at dipyrimidines containing 5-methylcytosine and only 2.2% of all mutations were transitions within this sequence context. However, 24% of the solar light-induced mutations were at dipyrimidines that contain 5-methylcytosine and most of them were transitions. Two sunlight-induced mutational hotspots at methylated CpGs correlated with sequences that form the highest levels of cyclobutane pyrimidine dimers after irradiation with sunlight but not with UVC. The data indicate that dipyrimidines that contain 5-methylcytosine are preferential targets for sunlight-induced mutagenesis in cultured mammalian cells, thus explaining the large proportion of p53 mutations at such sites in skin tumors in vivo.

Enterobacter asburiae KE17 association regulates physiological changes and mitigates the toxic effects of heavy metals in soybean.

This study aimed to elucidate the role played by Enterobacter asburiae KE17 in the growth and metabolism of soybeans during copper (100 µm Cu) and zinc (100 µm Zn) toxicity. When compared to controls, plants grown under Cu and Zn stress exhibited significantly lower growth rates, but inoculation with E. asburiae KE17 increased growth rates of stressed plants. The concentrations of plant hormones (abscisic acid and salicylic acid) and rates of lipid peroxidation were higher in plants under heavy metal stress, while total chlorophyll, carotenoid content and total polyphenol concentration were lower. While the bacterial treatment reduced the abscisic acid and salicylic acid content and lipid peroxidation rate of Cu-stressed plants, it also increased the concentration of photosynthetic pigments and total polyphenol. Moreover, the heavy metals induced increased accumulation of free amino acids such as aspartic acid, threonine, serine, glycine, alanine, leucine, isoleucine, tyrosine, proline and gamma-aminobutyric acid, while E. asburiae KE17 significantly reduced concentrations of free amino acids in metal-affected plants. Co-treatment with E. asburiae KE17 regulated nutrient uptake by enhancing nitrogen content and inhibiting Cu and Zn accumulation in soybean plants. The results of this study suggest that E. asburiae KE17 mitigates the effects of Cu and Zn stress by reprogramming plant metabolic processes.

Expression, purification, and characterization of a two domain carcinoembryonic antigen minigene (N-A3) in pichia pastoris. The essential role of the N-domain.

Carcinoembryonic antigen (CEA) is a 180 kDa glycoprotein expressed on the surface of normal and malignant human colon. The structure of CEA has seven predicted Ig-like domains (N-A1-B1-A2-B2-A3-B3) that are encoded by separate exons and contain independent epitopes that are recognized by monoclonal antibodies. The N-domain mediates homotypic cell adhesion as shown by deletion expression analysis, and may also interact with the A3 domain. Although we have been unsuccessful in expressing these domains in high yields of active protein in either bacterial or mammalian expression systems, we now report high yield expression in Pichia pastoris of a mini-gene (N-A3) comprising the N and A3 domains of CEA, and containing epitopes for the monoclonal antibodies T84.1 and T84.66. N-A3 was constructed by splice overlap PCR from the CEA gene and fused to the yeast alpha-mating factor leader sequence and an N-terminal His6 tag. The secreted protein gave high level expression (20 micrograms/mL) and was purified in two steps using Ni(NTA) affinity chromatography followed by reversed phase HPLC. The purified protein (yield 6 mg from 600 mL of supernatant) had a single N-terminal sequence, the expected amino acid composition, and retained full reactivity to both T84.1 and T84.66 compared to native CEA. BIAcore analysis gave a Kaff of 4.4 x 10(10) M-1 for the binding of N-A3 to T84.1 and 2.2 x 10(10) M-1 for the binding of N-A3 to T84.66. The molecular weight of N-A3 was 37 kDa before and 24 kDa after enzymatic deglycosylation as determined by SDS gel electrophoresis. The average N-glycosyl unit was calculated at 1850 Da (for 7 N-linked sites) suggesting a GN2Man9 oligosaccharide structure. N-A3 migrated as a dimer at 80 kDa and a monomer at 40 kDa on gel filtration analysis performed at pH 7.5, and 4.0, respectively. CEA exhibited the same conversion of dimers to monomers when analyzed by gel filtration at neutral and acid pH. The availability of this highly active CEA mini-gene should enable further structure-function studies including epitope analysis and investigation of monomer-dimer interactions.

Methylation of CpG dinucleotides in the lacI gene of the Big Blue transgenic mouse.

Cytosine residues at CpG dinucleotides can be methylated by endogenous methyltransferases in mammalian cells. The resulting 5-methylcytosine base may undergo spontaneous deamination to form thymine causing G/C to A/T transition mutations. Methylated CpGs also can form preferential targets for environmental mutagens and carcinogens. The Big Blue(R) transgenic mouse has been used to investigate tissue and organ specificity of mutations and to deduce mutational mechanisms in a mammal in vivo. The transgenic mouse contains approximately 40 concatenated lambda-like shuttle vectors, each of which contains one copy of an Escherichia coli lacI gene as a mutational target. lacI mutations in lambda transgenic mice are characterized by a high frequency of spontaneous mutations targeted to CpG dinucleotides suggesting an important contribution from methylation-mediated events. To study the methylation status of CpGs in the lacI gene, we have mapped the distribution of 5-methylcytosines along the DNA-binding domain and flanking sequences of the lacI gene of transgenic mice. We analyzed genomic DNA from various tissues including thymus, liver, testis, and DNA derived from two thymic lymphomas. The mouse genomic DNAs and methylated and unmethylated control DNAs were chemically cleaved, then the positions of 5-methylcytosines were mapped by ligation-mediated PCR which can be used to distinguish methylated from unmethylated cytosines. Our data show that most CpG dinucleotides in the DNA binding domain of the lacI gene are methylated to a high extent (>98%) in all tissues tested; only a few sites are partially (70-90%) methylated. We conclude that tissue-specific methylation is unlikely to contribute significantly to tissue-specific mutational patterns, and that the occurrence of common mutation sites at specific CpGs in the lacI gene is not related to selective methylation of only these sequences. The data confirm previous suggestions that the high frequency of CpG mutations in lacI transgenes is related to the presence of 5-methylcytosine bases.

[A clinical study on male patients with systemic lupus erythema].

To know the clinical characteristics of male patients with systemic lupus erythema(SLE), the clinical and laboratory indications of 46 male SLE patients were analysed and compared with those of 269 females. The results showed that: 1. There was family history in 21.28% of male patients. 2. As compared with female SLE patients, pleurisy, pericarditis, lupus nephritis(LN), proteinuria, renal failure, the incidence of types, V-LN and the positive rate of Sm antibody were more common in males while facial erythema, Raynaud's phenomenon and photoallergy were less in male. There were statistical differences between the male and female. 3. The confirmed diagnosis for the male SLE was delayed. The recovery rate was lower and the mortality was higher in males. These findings suggest that evident genetic predisposition, atypical clinical manifestations, serious renal injury and the worse prognosis are the characteristics of male SLE.

Cyclobutane pyrimidine dimers form preferentially at the major p53 mutational hotspot in UVB-induced mouse skin tumors.

The most prevalent DNA lesion induced by UV irradiation is the cyclobutane pyrimidine dimer (CPD) which forms at positions of neighboring pyrimidines. In mouse skin tumors induced by irradiation with UVB (280-320 nm) lamps or solar UV simulators, a major mutational hotspot occurs at codon 270 (Arg-->Cys) involving a sequence change from 5'-TCGT to 5'-TTGT. We have shown previously that CPD formation by UVB or sunlight is enhanced up to 10-fold at 5'-CCG and 5'-TCG sequences due to the presence of 5-methylcytosine bases. Sequence analysis showed that the CpG at codon 270 is methylated in mouse epidermis at a level of approximately 85%. Irradiation of mouse skin or mouse cells in culture produced the strongest CPD signal within exon 8 at the 5'-TCG sequence which is part of codon 270. Time course experiments showed that CPDs at this particular sequence persist longer than at several neighboring positions. The data suggest that formation of CPDs is responsible for induction of the major p53 mutational hotspot in UV-induced mouse skin tumors.

Oxidation of 2,4-dinitrophenol by hydrogen peroxide in the presence of basic oxygen furnace slag.

A treatment process was developed when basic oxygen furnace slag (BOF slag) and hydrogen peroxide were used to oxidize 2, 4-dinitrophenol from an aqueous solution. BOF slag, final waste slurry from steel making plants, contains about 12.5% by weight of ferrous oxide. In an acid solution, BOF slag can be dissociated to produce ferrous ions and react with hydrogen peroxide to produce hydroxyl radicals and oxidize 2,4-dinitrophenol. The results of the research demonstrated that the process had a significant capacity for oxidation of 2,4-dinitrophenol from the aqueous phase. Various factors critical to the oxidation of 2,4-dinitrophenol were studied, including hydrogen peroxide concentration, concentration of BOF slag, initial concentration of 2,4-dinitrophenol, and pH value of solution. Experimental results proved that 100 mg/L 2, 4-dinitrophenol and its oxidation intermediate could be totally decomposed within 60 min by 10 g/L BOF slag, 0.18 g/L hydrogen peroxide and pH 2.8 +/- 0.2. The optimum hydrogen peroxide concentration for degradation of 100 mg/L of 2,4-dinitrophenol is between 0.09 g/L and 0.18 g/L as 10 g/L BOF slag in the solution of pH 2.8 +/- 0.2. A hydrogen peroxide concentration higher than 0.18 g/L is disadvantageous to the oxidation process. The oxidation efficiency increased with the increase of BOF slag concentration at 0.18 g/L hydrogen peroxide dose. The best pH value of the solution is in the vicinity of 2.8. An oxidation reaction mechanism was proposed for predicting the concentration changes of 2, 4-dinitrophenol, ferrous ion, and hydrogen peroxide.http://link. springer-ny.com/link/service/journals/00244/bibs/37n4p427.++ +html

Cyclobutane pyrimidine dimers are responsible for the vast majority of mutations induced by UVB irradiation in mammalian cells.

The most prevalent DNA lesions induced by UVB are the cyclobutane pyrimidine dimers (CPDs) and the pyrimidine (6-4) pyrimidone photoproducts ((6-4)PPs). It has been a long standing controversy as to which of these photoproduct is responsible for mutations in mammalian cells. Here we have introduced photoproduct-specific DNA photolyases into a mouse cell line carrying the transgenic mutation reporter genes lacI and cII. Exposure of the photolyase-expressing cell lines to photoreactivating light resulted in almost complete repair of either CPDs or (6-4)PPs within less than 3 h. The mutations produced by the remaining, nonrepaired photoproducts were scored. The mutant frequency in the cII gene after photoreactivation by CPD photolyase was reduced from 127 x 10(-5) to 34 x 10(-5) (background, 8-10 x 10(-5)). Photoreactivation with (6-4) photolyase did not lower the mutant frequency appreciably. In the lacI gene the mutant frequency after photoreactivation repair of CPDs was reduced from 148 x 10(-5) to 28 x 10(-5) (background, 6-10 x 10(-5)). Mutation spectra obtained with and without photoreactivation by CPD photolyase indicated that the remaining mutations were derived from background mutations, unrepaired CPDs, and other DNA photopoducts including perhaps a small contribution from (6-4)PPs. We conclude that CPDs are responsible for at least 80% of the UVB-induced mutations in this mammalian cell model.