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1.
Article in English | MEDLINE | ID: mdl-38029665

ABSTRACT

Diabetic kidney disease (DKD), a common microvascular complication of diabetes, currently lacks specific diagnostic indicators and therapeutic targets, resulting in miss of early intervention. To profile metabolic conditions in complex and precious biological samples and screen potential biomarkers for DKD diagnosis and prognosis, a rapid, convenient and reliable quantification method for carboxyl compounds by gas chromatography-mass spectrometry (GC-MS) was established with isobutyl chloroformate derivatization. The derivatives were extracted with hexane, injected into GC-MS and quantified with selected ion monitoring mode. This method showed excellent linearity(R2 > 0.99), good recoveries (81.1%-115.5%), good repeatability (RSD < 20%) and sensitivity (LODs: 0.20-499.90 pg, LOQs: 2.00-1007.00 pg). Among the 37 carboxyl compounds analyzed, 12 metabolites in short-chain fatty acids (SCFAs) metabolism pathway and amino acid metabolism pathway were linked with DKD development and among them, 6 metabolites were associated with both development and prognosis of DKD in mice. In conclusion, a reliable, convenient and sensitive method based on isobutyl chloroformate derivatization and GC-MS analysis is established and successfully applied to quantify 37 carboxyl compounds in biological samples of mice and 12 potential biomarkers for DKD development and prognosis are screened.


Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Humans , Gas Chromatography-Mass Spectrometry/methods , Diabetic Nephropathies/diagnosis , Formates/chemistry , Biomarkers
2.
Ann Dermatol ; 35(Suppl 1): S79-S83, 2023 May.
Article in English | MEDLINE | ID: mdl-37853872

ABSTRACT

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is an extremely rare, indolent skin malignancy that can be difficult to distinguish from autoimmune disease-associated panniculitides. Here, we describe a 12-year-old boy who was diagnosed at age 7 years with dermatomyositis with classical manifestations, including poikiloderma, Gottron's sign, and symmetric muscle weakness. Recently, the boy presented multiple subcutaneous nodules and fever. Histopathological examination and immunohistochemical staining revealed coexistence of SPTL. To our knowledge, this is the first case of dermatomyositis accompanied with SPTL. This case alert clinical physicians of the possibility of SPTL should be considered when a patient with dermatomyositis has new lesions presenting as nodules and unknown fever.

3.
World J Clin Cases ; 11(21): 5187-5192, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37583865

ABSTRACT

BACKGROUND: Brucellosis is one of the most common zoonotic infectious diseases in the world, with approximately 500000 new cases of human brucellosis diagnosed each year. Brucellosis can simulate various multi-system diseases, presenting atypical symptoms. Very few brucellosis cases with pancytopenia accompanied by a severe hearing loss have been reported. In the literature review, we could find only one similar case reported in the past. Moreover, this disease is easily misdiagnosed as a blood system disease leading to delayed treatment. Thus, it is important to improve clinicians' awareness of this disease. CASE SUMMARY: A 64-year-old woman presented with dizziness and fatigue, accompanied by pancytopenia and severe hearing loss. Brucella melitensis was identified on blood culture. Anti-infective therapy with rifampicin (900 mg/d) and doxycycline (100 mg twice a day) was prescribed for 4 mo along with ceftriaxone 2 g/d for 1 mo. The patient showed a good response to antibiotic therapy. Her blood counts returned to normal followed by significant improvement in hearing. CONCLUSION: Brucellosis should be considered in the differential diagnosis of patients presenting with pancytopenia and hearing loss.

5.
J Pharm Biomed Anal ; 229: 115351, 2023 May 30.
Article in English | MEDLINE | ID: mdl-36958114

ABSTRACT

Compounds such as Sildenafil, which bring potential health risks to consumers, have been illegally added to functional food. The public security department hopes to quickly screen for illegal additives. The quantity of seized samples is often large and their compositions are unknown; it is necessary to screen the unknown samples qualitatively and sometimes quantitatively. In this paper, a new method for rapid screening of 39 common illegal additives in six categories of functional food based on DESI-MSI technology is proposed, and the DESI-MSI library is established, which can be used for exclusive and sensitive qualitative confirmation of suspicious samples. A new carrier material that can be used for rapid qualitative detection of solid sample is discovered. The samples require simple or even no pretreatment to carry out high-resolution imaging through the imaging function of DESI-MSI. The imaging results are clear and intuitive, and can achieve fast and high-throughput qualitative identification of illegally added compounds. This method has good linearity, accuracy, precision, and little effect of matrix, so it can roughly quantify the illegal additives in functional products. Twenty-one batches of unknown samples were detected by DESI-MSI, and the positive results were confirmed by LC-MS/MS (QQQ). The results showed that the DESI-MSI method was effective and reliable. DESI-MSI with self-made database is a promising method for rapid screening of illegal additives in functional food, which can be widely used in grass-roots police stations.


Subject(s)
Spectrometry, Mass, Electrospray Ionization , Tandem Mass Spectrometry , Spectrometry, Mass, Electrospray Ionization/methods , Chromatography, Liquid , Functional Food
6.
Forensic Toxicol ; 41(1): 126-134, 2023 01.
Article in English | MEDLINE | ID: mdl-36652071

ABSTRACT

PURPOSE: This study aims to develop and validate a rapid, simple, and efficient bioanalytical method for the simultaneous quantification of phenobarbital and barbital in human whole blood using liquid-liquid extraction combined with direct analysis in real time (DART) and high-resolution mass spectrometry (HRMS). METHOD: Phenobarbital-d5 and aprobarbital were selected as internal standards (ISs) of phenobarbital and barbital, respectively. A mixed solvent of o-xylene and ethyl acetate at a ratio of 1:6 was used to extract analytes of interest and ISs from 100 µL of human whole blood samples. Phenobarbital and barbital were detected by DART-HRMS. The proposed method has been validated in accordance with United States Food and Drug Administration Guidelines for Bioanalytical Method Validation in terms of selectivity, linearity, accuracy, precision, matrix effect, recovery, stability, and dilution integrity. RESULTS: The lower limits of quantification (LLOQs) of phenobarbital and barbital were both 10 ng/mL. The linearities were in the range of 10-1000 ng/mL (R2 ≥ 0.99). The mean recovery values of phenobarbital and barbital were 99.7% and 88.1%, respectively. The interday and intraday precision values were less than 10.4%, and the interday and intraday accuracy values ranged from 87.6 to 106.7%. Furthermore, the validated method was applied to four cases of phenobarbital poisoning at the Shanghai Institute of Forensic Science. CONCLUSION: The developed and fully validated method enabled the simultaneous quantification of phenobarbital and barbital in human whole blood and was successfully applied to authentic cases.


Subject(s)
Barbital , Phenobarbital , United States , Humans , China , Mass Spectrometry/methods , Liquid-Liquid Extraction
7.
Anticancer Agents Med Chem ; 23(3): 306-316, 2023.
Article in English | MEDLINE | ID: mdl-35598248

ABSTRACT

AIM: The main aim of this study is to improve the solubility, reduce side effects and increase the therapeutic efficacy of CSL by using functionalized graphene oxide as a carrier, to fulfill chemo-photothermal therapy. BACKGROUND: Celastrol (CSL), which is extracted from the traditional Chinese medicinal plant Tripterygium wilfordii, has reported significant antitumor activity in vitro and in vivo cancer models. However, disadvantages with regard to solubility, short plasma half-life and toxicity hinder its use in pharmaceutical application. Nanocarrier delivery system could be employed to improve the biochemical and pharmacokinetic performance of CSL. Among numerous nanocarriers, graphene oxide is one of the most promising nanocarriers due to its intrinsic physical and chemical properties and good biocompatibility. OBJECTIVE: Here, we employed a PEGylated reduced nanographene oxide CSL complex (nrGO-PEG/CSL) as a new drug delivery system to achieve highly efficient synergistic chemo/photothermal therapy. METHODS: A functionalized nrGO-PEG was synthesized and the loading capacity of CSL, photothermal effect and release efficiency under different pH and NIR irradiation were measured in the first stage of work. In vitro and in vivo anticancer effects of prepared nrGO-PEG/CSL complex were evaluated on 4T1 cells and 4T1 tumor-bearing mice, respectively, with the association of NIR laser irradiation. RESULTS: The functionalized nrGO-PEG exhibited excellent drug loading capacity of CSL (20.76 mg/mg GO) and photothermal effect (~3.0 -fold increment over unreduced nGO-PEG). Loaded CSL could be efficiently released from nrGO-PEG/CSL complex by NIR irradiation in vitro. In vivo study performed on 4T1 tumor-bearing mice proved that nrGO-PEG/CSL with NIR laser irradiation shows superior anticancer effects. CONCLUSION: The experimental data demonstrated that the nrGO-PEG/CSL-mediated chemo/photothermal combination therapy was more cytotoxic to cancer cells than only chemotherapy or photothermal treatment, reducing the occurrence of tumor metastasis. Therefore, nrGO-PEG/CSL-mediated chemo/photothermal is expected to be a promising treatment for synergistic cancer therapy.


Subject(s)
Neoplasms , Oxides , Animals , Mice , Oxides/pharmacology , Oxides/chemistry , Photothermal Therapy , Phototherapy , Polyethylene Glycols/chemistry
8.
RSC Adv ; 12(46): 29688-29696, 2022 Oct 17.
Article in English | MEDLINE | ID: mdl-36321092

ABSTRACT

Light and flexible electromagnetic-interference-shielding materials are of great significance to control electromagnetic pollution and protect the human body and other nearby equipment or systems. In this study, a film of polytetrafluoroethylene wrapped with copper (PTFE@Cu) was prepared by depositing Cu using electroless plating on the surface of a microporous PTFE film modified by dopamine. A Ni@PVDF membrane was fabricated by casting a suspension of Ni nanochains in PVDF. The two kinds of films were hot-pressed into an ultrathin and efficient electromagnetic-shielding film with a sandwich structure. PTFE and PVDF provided high flexibility to the composite film, while the metal-wrapped polymer fiber structure gave the film an excellent electromagnetic-shielding efficiency, and the Ni nanochains and laminated hot-pressing process further enhanced the shielding ability of the film. Through these combined effects, the conductivity of the composite film reached 1117.57 S cm-1 while the thickness was only about 80 µm, and the average shielding efficiency in the X-band range was as high as 57.16 dB with absorption accounting for about 67.2% of the total shielding. At the same time, the composite film had high strength and flexibility, and the tensile strength could reach 43.49 MPa. Even after bending 1000 times, the conductivity could still be maintained at 174.55 S cm-1, while the average shielding effectiveness in the X-band range was retained at 44.29 dB. The film has great latent applications in flexible devices and portable wearable intelligent devices.

9.
Front Pharmacol ; 13: 885386, 2022.
Article in English | MEDLINE | ID: mdl-36105186

ABSTRACT

Background: Metabolomics can be applied to the clinical diagnosis and treatment evaluation of acquired immune deficiency syndrome (AIDS). AIDS biomarkers have become a new direction of AIDS research providing clinical guidance for diagnosis. Objective: We sought to apply both untargeted and targeted metabolomic profiling to identify potential biomarkers for AIDS patients. Methods: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) based untargeted metabolomic profiling was performed on plasma samples of patients before and after highly active antiretroviral therapy (HAART) treatment as well as healthy volunteers to identify potential AIDS biomarkers. Targeted quantitative analysis was performed on the potential biomarkers screened from untargeted metabolic profiling for verification. Results: Using the Mass Profiler Professional and the MassHunter, several potential biomarkers have been found by LC-MS/MS in the untargeted metabolomic study. High-resolution MS and MS/MS were used to analyze fragmentation rules of the metabolites, with comparisons of related standards. Several potential biomarkers have been identified, including PS(O-18:0/0:0), sphingosine, PE (21:0/0:0), and 1-Linoleoyl Glycerol. Targeted quantitative analysis showed that sphingosine and 1-Linoleoyl Glycerol might be closely related to HIV/AIDS, which may be the potential biomarkers to the diagnosis. Conclusion: We conducted untargeted metabolomic profiling, which indicates that several metabolites should be considered potential biomarkers for AIDS patients. Further targeted metabolomic research verified that d-Sphingosine and 1-Linoleoyl glycerol as the diagnostic biomarker of AIDS.

10.
Clin Oral Investig ; 26(8): 5205-5213, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35441898

ABSTRACT

OBJECTIVES: This study was designed to explore the effects of mechanical force on the proliferation, apoptosis, and morphology of stem cells from human exfoliated deciduous tooth pulp (SHEDs). MATERIALS AND METHODS: Caries-free stranded deciduous teeth were extracted, and SHEDs were isolated through enzymatic digestion. The cultured SHEDs were subjected to different levels of mechanical stimuli (0, 100, 200, and 300 g) for 7 days (30 min/day) using external centrifugal force. Cell proliferation was evaluated with the CCK-8 assay, and the cell cycle and apoptosis were assessed by flow cytometry. The cell morphology was examined using transmission electron microscopy. RESULTS: Cell proliferation assay showed no differences between the three stimulation groups and the control group in day 1 to day 3. From the 4th day, cell proliferation was significantly lower in the mechanical force groups than in the control group, but no significant difference was observed among the three mechanical force groups. Besides, there was no significant difference in cell apoptosis among the four groups for 7 days. On day 7 after stimulation, the SHEDs were shrunken, with significantly increased isochromosome in the nucleus and an increase in lysosomes. CONCLUSIONS: Mechanical force can inhibit the proliferation and affect morphology of SHEDs, but it has no effect on cell apoptosis. CLINICAL RELEVANCE: Mechanical force stimulation significantly inhibited cell proliferation of SHEDs. Mechanical force stimulation had no significant effect on cell apoptosis of SHEDs. The morphology and ultrastructure of SHEDs changed after mechanical force stimulation.


Subject(s)
Stem Cells , Tooth, Deciduous , Apoptosis , Cell Differentiation , Cell Proliferation , Cells, Cultured , Dental Pulp , Humans
11.
EMBO Mol Med ; 14(5): e14904, 2022 05 09.
Article in English | MEDLINE | ID: mdl-35362222

ABSTRACT

In this report, we discovered a new entity named cataract, alopecia, oral mucosal disorder, and psoriasis-like (CAOP) syndrome in two unrelated and ethnically diverse patients. Furthermore, patient 1 failed to respond to regular treatment. We found that CAOP syndrome was caused by an autosomal recessive defect in the mitochondrial membrane-bound transcription factor peptidase/site-1 protease (MBTPS1, S1P). Mitochondrial abnormalities were observed in patient 1 with CAOP syndrome. Furthermore, we found that S1P is a novel mitochondrial protein that forms a trimeric complex with ETFA/ETFB. S1P enhances ETFA/ETFB flavination and maintains its stability. Patient S1P variants destabilize ETFA/ETFB, impair mitochondrial respiration, decrease fatty acid ß-oxidation activity, and shift mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis. Mitochondrial dysfunction and inflammatory lesions in patient 1 were significantly ameliorated by riboflavin supplementation, which restored the stability of ETFA/ETFB. Our study discovered that mutations in MBTPS1 resulted in a new entity of CAOP syndrome and elucidated the mechanism of the mutations in the new disease.


Subject(s)
Cataract , Psoriasis , Alopecia/genetics , Cataract/genetics , Electron-Transferring Flavoproteins/genetics , Electron-Transferring Flavoproteins/metabolism , Humans , Riboflavin/metabolism
12.
J Pharm Biomed Anal ; 214: 114722, 2022 May 30.
Article in English | MEDLINE | ID: mdl-35325799

ABSTRACT

Pharmaceutical drugs like Sildenafil are illegally added to functional food such as nutritional supplements and herbal remedies to deliver drugs without a regular prescription to consumers. Rapid screening of illegal additives is desirable for the public security department. The seized samples are often large in number and unknown in composition; methods are needed for qualitative screening of unknown samples. Here, a new approach is presented based on atmospheric pressure solids analysis probe (ASAP) coupled with single-quadrupole mass spectrometer to rapidly screen 42 common illegal additives in six categories of functional food. The ASAP-MS method could be applied to solid or liquid sample analysis with a very simple pre-treatment and no LC chromatographic separation, using a home-built library; the identification of suspicious additives could be obtained rapidly. More importantly, the approach is sensitive enough for complex matrix samples like coffee samples. 21 batches of seized unknown samples were tested by the ASAP-MS, and the positive results were confirmed by LC-MS/MS(QQQ), indicating that the ASAP-MS method is effective and reliable. The ASAP-MS with home-built library is a promising method for rapid screening of illegal additives in functional food, which could be widely used in the grassroots police station that lack professional laboratory environment.


Subject(s)
Functional Food , Tandem Mass Spectrometry , Atmospheric Pressure , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid
13.
J Control Release ; 344: 62-79, 2022 04.
Article in English | MEDLINE | ID: mdl-35182612

ABSTRACT

Low levels of accumulation and permeability in tumors are two primary reasons for the limited efficacy of conventional antineoplastic nanodrugs. In the present study, based on an original corosolic acid liposome (CALP) carrier with the functions of cell penetration, tumor permeability and anti-inflammation developed by our previous work, a versatile PTX/CALP was achieved by CALP loading paclitaxel (PTX). Compared to conventional PTX liposomes (PTX/LP) prepared by cholesterol and phospholipid, PTX/CALP exhibited extremely increasing cellular uptake and cytotoxicity in vitro, and in vivo enhancing the accumulation and permeability of tumor, thus significantly improving the antitumor efficacy. Further evidence indicated that PTX/CALP conspicuously promoted the recruitment of CD8+ T cells as well as reduced the infiltration of regulatory T cells and M2 macrophages into tumor by inducing enhanced immunogenic cell death (ICD) and down-regulating the inflammation level. Therefore, the improvement of efficacy was also attributed to the superiorities of PTX/CALP in modulating the inflammatory and immunosuppressive tumor microenvironment. Overall, the smart PTX liposomes based on the multi-functional CALP carrier without any modification could overcome the harsh tumor biological barriers, enhance the induction of ICD and then achieve satisfactory efficacy, suggesting its promising potentials in industrial transfer and clinical application.


Subject(s)
Antineoplastic Agents, Phytogenic , Liposomes , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , CD8-Positive T-Lymphocytes , Cell Line, Tumor , Liposomes/therapeutic use , Mice , Mice, Inbred BALB C , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Tumor Microenvironment
14.
J Dermatol ; 49(1): 161-164, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34601768

ABSTRACT

Germline mutations in HRAS cause Costello syndrome (CS), while mosaic mutations in HRAS show a variability of phenotypes, ranging from mild features such as keratinocytic epidermal nevus (KEN), sebaceous nevus (SN), woolly hair nevus (WHN) with KEN, to severe manifestations of CS with cutis laxa. We report two individuals. The first was a 2-year-old boy with woolly hair nevus (WHN) without any other cutaneous involvement, in whom somatic HRAS mutation (c.34G>A; p.Gly12Ser) was identified in his affected scalp and hair follicle specimens. This is the first reported WHN type 1 (no cutaneous involvement) patient caused by somatic HRAS mutation. The other individual was a 12-year-old girl with CS caused by germline HRAS mutation (c.34G>A), that manifested with coarse face, palmoplantar keratoderma, deep palmar and plantar creases, hyperpigmented patches, asymmetry and deformity of lower limbs, atopic dermatitis, as well as mental retardation. Of note, a linear hyperpigmented plaque was observed in her father's lumbosacral region. Although the father refused to provide semen and skin tissue for further examination, this reminds us of possible mosaicism in parents of individuals with germline de novo HRAS mutation and underlines the importance of parental evaluation for prenatal counseling.


Subject(s)
Costello Syndrome , Nevus , Child , Child, Preschool , Costello Syndrome/genetics , Counseling , Female , Germ-Line Mutation , Humans , Male , Mosaicism , Mutation , Parents , Pregnancy , Proto-Oncogene Proteins p21(ras)/genetics
15.
Clin Genet ; 101(1): 110-115, 2022 01.
Article in English | MEDLINE | ID: mdl-34494659

ABSTRACT

The treatment of recessive dystrophic epidermolysis bullosa (RDEB) remains challenging. Elevated IgE levels have previously been reported in several RDEB patients. In this prospective, single-centre, open intervention study, elevated IgE levels were seen in 11 out of 12 patients with intense pruritus, and the patients with elevated IgE levels received anti-IgE therapy every 4 weeks for at least three cycles. Compared with the baseline, 10 patients with RDEB had good clinical outcomes with enhanced wound healing, a reduction in Birmingham (epidermolysis bullosa) EB severity score by 15%, a reduction in affected body surface area by 23.3%, amelioration of skin inflammation, and an increase in type VII collagen deposition by 13.1-fold. All the patients had a good tolerance to anti-IgE therapy. Furthermore, patients with higher IgE levels tended to have higher disease severity and more favorable clinical outcomes. Our report also suggested the potential role of IgE in the pathogenesis of inflammatory conditions associated with RDEB. (ChiCTR1900021437).


Subject(s)
Antibodies, Anti-Idiotypic/therapeutic use , Epidermolysis Bullosa Dystrophica/drug therapy , Adolescent , Adult , Antibodies, Anti-Idiotypic/administration & dosage , Antibodies, Anti-Idiotypic/adverse effects , Autoimmunity , Biopsy , Child , Collagen Type VII/immunology , Disease Management , Disease Susceptibility/immunology , Epidermolysis Bullosa Dystrophica/diagnosis , Epidermolysis Bullosa Dystrophica/etiology , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Middle Aged , Severity of Illness Index , Skin/immunology , Skin/metabolism , Skin/pathology , Treatment Outcome , Wound Healing , Young Adult
16.
Lancet Infect Dis ; 22(3): e93-e100, 2022 03.
Article in English | MEDLINE | ID: mdl-34838200

ABSTRACT

Cutaneous infection by Balamuthia mandrillaris is a rare condition that is sometimes complicated by life-threatening CNS involvement. It often evades timely diagnosis due to its rarity and non-specific clinical manifestations. Patients can be either immunocompetent or immunocompromised. It is probably transmitted via inhalation or inoculation through broken skin, and then spreads to the brain and other organs through haematogenous spread. It is important for clinicians to be aware of this disease because rapid diagnosis and subsequent therapy has, in some cases, been associated with survival. In this Grand Round, we report the case of a 7-year-old boy who presented with large, chronic plaques on his face. Several biopsies showed non-specific granulomatous inflammation. The patient deteriorated rapidly and died within 1 month of displaying abnormal symptoms in the CNS. Immunohistochemical staining of skin tissue identified B mandrillaris as the infectious agent. The diagnosis was confirmed with PCR, which detected B mandrillaris DNA in formalin-fixed skin tissue sections. B mandrillaris infection should be considered in the differential diagnosis of patients with chronic granulomatous lesions. We also reviewed the epidemiology, B mandrillaris in nature and in the laboratory, clinical manifestations, histopathology, diagnosis, and treatment of infection.


Subject(s)
Amebiasis , Balamuthia mandrillaris , Amebiasis/diagnosis , Amebiasis/drug therapy , Amebiasis/pathology , Brain/diagnostic imaging , Brain/pathology , Child , Face/pathology , Granuloma , Humans , Male
17.
ACS Appl Mater Interfaces ; 13(34): 40648-40655, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34427076

ABSTRACT

Three double D-π-A sensitizers (A1, A3, and A5) containing different donors (triphenylamine, methoxy-modified triphenylamine, and cyclic thiourea-functionalized triphenylamine) are synthesized to investigate the role of different donors in dye-sensitized solar cells (DSSCs). Detailed investigations of the sensitizers reveal that the spatial characteristics of donor units have a considerable impact on the light-harvesting, electrochemistry, and photovoltaic properties. Benefiting from the strong shielding ability of alkyl chains in the donor to its branch chains as observed in density functional theory (DFT), the open-circuit voltage (VOC = 712.0 mV) of A5-based DSSC is higher than those of A1 and A3 by 90 and 78 mV, respectively. Therefore, the A5-based DSSC delivers a good efficiency of 8.54%, relying on its effective suppression of interfacial recombination. The results indicate that the judiciously tailored donor unit is an effective approach to optimize dye configurations to further improve power conversion efficiencies.

18.
Eur J Dermatol ; 31(2): 239-244, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33818390

ABSTRACT

BACKGROUND: Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome comprise a rare genodermatosis associated with biallelic (homozygous or compound heterozygous) mutations in the DSG1 (desmoglein-1) gene, or heterozygous mutations in the DSP (desmoplakin) gene. To date, while many patients with SAM syndrome have been described, the number of cases with SAM syndrome with deep-intronic variants, together its genetic aetiology, remain limited. OBJECTIVES: We report the case of a five-year-old Chinese boy with atypical SAM syndrome. MATERIALS & METHODS: Relevant blood specimens from the family were collected. DNA isolation, RNA isolation and cDNA synthesis, and next-generation sequencing using a multi-gene panel were applied to verify the pathogenic gene. To test the functional consequences and pathogenic mechanism of the deep-intronic mutation in vitro, a mini gene strategy was constructed. RESULTS: A heterozygous DSG1 deletion (c.2437_2450delACCTATCCCTCGGG: p.Tyr814Trpfs*6) and a deep-intronic (c.1688-30A > T) variant were identified. The identified intronic variant was shown to create an alternative splice site, leading to nonsense-mediated mRNA decay of the aberrant transcript. CONCLUSION: This is the first study to demonstrate a causal role for a deep-intronic DSG1 mutation in a patient with SAM syndrome. Our findings underline the need to analyse the intronic regions of DSG1 in patients with SAM syndrome. Improved diagnosis and a better understanding of prognosis will lead to clearer a picture of the concept of atypical SAM syndrome.


Subject(s)
Dermatitis/genetics , Desmoglein 1/genetics , Hypersensitivity/genetics , Metabolic Diseases/genetics , Child, Preschool , Dermatitis/pathology , Desmoglein 1/metabolism , Epidermis/metabolism , Female , Frameshift Mutation , Heterozygote , Humans , Introns , Male , Pedigree , Syndrome
19.
Blood Adv ; 5(5): 1250-1258, 2021 03 09.
Article in English | MEDLINE | ID: mdl-33646303

ABSTRACT

Refractory prolonged isolated thrombocytopenia (RPIT) is an intractable complication after allogeneic hematopoietic cell transplantation (HCT), which often leads to poor prognosis. A clinical study was designed to validate the efficacy and safety of low-dose decitabine for RPIT after HCT and explore the related underlying mechanisms. Eligible patients were randomly allocated to receive 1 of 3 interventions: arm A, low-dose decitabine (15 mg/m2 daily IV for 3 consecutive days [days 1-3]) plus recombinant human thrombopoietin (300 U/kg daily); arm B, decitabine alone; or arm C, conventional treatment. The primary end point was the response rate of platelet recovery at day 28 after treatment. Secondary end points included megakaryocyte count 28 days after treatment and survival during additional follow-up of 24 weeks. Among the 91 evaluable patients, response rates were 66.7%, 73.3%, and 19.4% for the 3 arms, respectively (P < .001). One-year survival rates in arms A (64.4% ± 9.1%) and B (73.4% ± 8.8%) were similar (P = .662), and both were superior to that in arm C (41.0% ± 9.8%; P = .025). Megakaryocytes, endothelial cells (ECs), and cytokines relating to megakaryocyte migration and EC damage were improved in patients responding to decitabine. This study showed low-dose decitabine improved platelet recovery as well as overall survival in RPIT patients after transplantation. This trial was registered at www.clinicaltrials.gov as #NCT02487563.


Subject(s)
Myelodysplastic Syndromes , Thrombocytopenia , Decitabine , Endothelial Cells , Humans , Thrombocytopenia/drug therapy , Thrombocytopenia/etiology , Thrombopoietin
20.
Materials (Basel) ; 13(17)2020 Aug 31.
Article in English | MEDLINE | ID: mdl-32878129

ABSTRACT

This paper presents a method based on signal correlation to detect delamination defects of widely used carbon fiber reinforced plastic with high precision and a convenient process. The objective of it consists in distinguishing defect and non-defect signals and presenting the depth and size of defects by image. A necessary reference signal is generated from the non-defect area by using autocorrelation theory firstly. Through the correlation calculation results, the defect signal and non-defect signal are distinguished by using Euclidean distance. In order to get more accurate time-of-flight, cubic spline interpolation is introduced. In practical automatic ultrasonic A-scan signal processing, signal correlation provide a new way to avoid problems such as signal peak tracking and complex gate setting. Finally, the detection results of a carbon fiber laminate with artificial delamination through ultrasonic phased array C-scan acquired from Olympus OmniScan MX2 and this proposed algorithm are compared, which showing that this proposed algorithm performs well in defect shape presentation and location calculation. The experiment shows that the defect size error is less than 4%, the depth error less than 3%. Compared with ultrasonic C-scan method, this proposed method needs less inspector's prior-knowledge, which can lead to advantages in automatic ultrasonic testing.

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