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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 1271-1277, 2024 Aug.
Article in Chinese | MEDLINE | ID: mdl-39192430

ABSTRACT

OBJECTIVE: To explore the key factors affecting plasma clot retraction and optimize the experimental method of plasma clot retraction, in order to study the regulation of platelet function and evaluate the modulatory effects of drugs on plasma clot retraction. METHODS: The effects of different concentrations of thrombin, Ca2 + and platelets on plasma clot retraction were studied, and the detection system of plasma clot retraction was optimized. The availability of the detection system was then validated by analyzing the regulatory effects of multiple signaling pathway inhibitors on plasma clot retraction. RESULTS: Through the optimization study of multiple factors, platelet rich plasma (PRP) containing 0.5 mmol/L Ca2 + and 40×109/L platelets was treated with 0.2 U/ml thrombin to perform plasma clot retraction analysis. After treatment with thrombin for 15 min, plasma clot retracted significantly. After treatment with thrombin for 30 min, the percentage of plasma clot retraction was more than 50%. The regulatory effects of multiple signaling pathway inhibitors on plasma clot retraction were studied in this detection system. PKC inhibitor Go 6983 exhibited a significant inhibitory effect on plasma clot retraction, while PI3K inhibitor Ly294002 and p38 MAPK inhibitor SB203580 slightly suppressed plasma clot retraction. CONCLUSION: PRP containing 0.5 mmol/L Ca2 + and 40×109/L platelets can be induced with 0.2 U/ml thrombin to conduct plasma clot retraction analysis, which can be used to study the regulation of platelet function and evaluate the modulatory effects of drugs on plasma clot retraction.


Subject(s)
Blood Platelets , Clot Retraction , Platelet-Rich Plasma , Thrombin , Humans , Thrombin/pharmacology , Signal Transduction , Blood Coagulation , Calcium , Pyridines/pharmacology , Morpholines/pharmacology , Chromones/pharmacology , Plasma , Imidazoles/pharmacology
2.
Dermatol Ther (Heidelb) ; 14(9): 2479-2493, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39103673

ABSTRACT

INTRODUCTION: The burden of atopic dermatitis (AD) is significant, with a substantial impact on quality of life (QoL). This cross-sectional study aimed to ascertain the burden of AD, its impact on QoL, and associated costs. METHODS: Patients with moderate-to-severe AD were enrolled from eight territories, namely Hong Kong, India, Japan, Mainland China, Singapore, South Korea, Taiwan, and Thailand. After screening was performed and informed consent was obtained, eligible participants were asked to provide responses on their AD symptoms, severity, treatment, and out-of-pocket costs via an online survey. QoL was assessed using EQ-5D-5L and Dermatology Life Quality Index (DLQI), while productivity loss was quantified using the Work Productivity and Activity Impairment (WPAI) questionnaire. Data from completed submissions were analyzed using descriptive statistics. The study was reviewed by the institutional review board in each territory. RESULTS: Median age of enrolled patients (N = 1103) was 41.0 years (interquartile range, IQR 16.0). The majority of patients reported that their head/neck, trunk, upper limbs, and lower limbs were affected during a flare. Topical (74.2%) and oral steroids (58.7%) were frequently prescribed to manage AD. Common atopic comorbidities were allergic urticaria (64.2%), allergic rhinitis (61.8%), and allergic conjunctivitis (51.5%). Median DLQI score was 13.0 (IQR 11.0), while median EQ-5D-5L (based on China value set) score was 0.8 (IQR 0.4); 87.2% and 77.2% of patients reported pain/discomfort and anxiety/depression on the EQ-5D-5L domains, respectively. Median total annual costs associated with AD were USD 10,128.52 (IQR 12,963.26) per patient, with indirect costs being the largest component. Findings from WPAI indicated that presenteeism is a major contributor to productivity loss. CONCLUSION: This multinational survey study showed that AD is associated with substantial QoL impairment and economic burden among Asian adult patients with moderate-to-severe AD. To alleviate burden of AD, clinicians should be more proactive in managing other concomitant conditions including psychological issues, and advocate for increased reimbursement for AD treatments.

3.
Dermatol Ther (Heidelb) ; 14(9): 2559-2576, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39162764

ABSTRACT

INTRODUCTION: Limited evidence is available on real-world management of atopic dermatitis (AD) among Asian adults. This cross-sectional study aimed to assess current approaches in AD diagnosis and management in Asia. METHODS: Practising dermatologists regularly treating patients with moderate-to-severe AD were recruited from eight Asia-Pacific territories, namely Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand. A survey was administered to eligible dermatologists after screening and taking informed consent. Data from fully completed submissions were analysed using descriptive statistics. The study was reviewed by the institutional review board in each territory. RESULTS: Data from 271 dermatologists were included for analysis. About one-third (31.7%) reported that they referred to the Hanifin and Rajka criteria during diagnosis. The majority of dermatologists used clinical impression when assessing AD severity and treatment response. Reduction of eczema and pruritus was the primary treatment objective when managing both acute (98.1%) and chronic (69.1%) AD. More than half of dermatologists preferred adding systemic anti-inflammatory medication for patients who did not respond to maximized topical treatment, while 43.6% would switch to another systemic medication for those failing to respond to maximized systemic treatment. Topical corticosteroids were frequently selected by dermatologists. For systemic therapies, oral corticosteroids were most frequently used, followed by cyclosporin and dupilumab. Narrow-band ultraviolet B was the most common phototherapy reported (84.9%). There was considerable variation in estimated average and maximum durations of therapies used to treat AD. CONCLUSION: This study has provided insights on the real-world management of moderate-to-severe AD in the Asia-Pacific region. The diverse approaches in diagnosis and treatment highlight the multifactorial nature of AD, reliance on clinical judgement, and importance of personalized care. To improve outcomes in patients with AD, it will be crucial to develop biomarkers for diagnosis, reduce subjectivity in assessment, as well as promote access to newer and effective therapies.

4.
Dermatol Ther (Heidelb) ; 14(8): 2195-2208, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39008225

ABSTRACT

INTRODUCTION: It remains unclear how patients with atopic dermatitis (AD) and clinicians perceive the level of patient-clinician communication and if there could be potential lapses. This cross-sectional study aims to compare perspectives between patients with AD and dermatologists regarding communication and treatment expectations in Asia. METHODS: Moderate-to-severe patients with AD and practicing dermatologists were recruited from eight Asia-Pacific territories, including Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand. Patients and dermatologists completed separate surveys designed to elicit their expectations regarding AD management, and their perceived level of patient-clinician communication. Patients were also asked about their treatment satisfaction and whether they prefer additional treatment beyond what was prescribed. Demographic information and responses were analyzed using descriptive statistics. The study was reviewed by the institutional review board in each territory, and all participants provided informed consent. RESULTS: A total of 1103 patients and 271 dermatologists completed the surveys. Both patients and dermatologists were largely aligned in their top treatment goals in AD management. However, greater proportions of patients prioritized the prevention of exacerbation (78.0% versus 47.2%), minimization of treatment adverse effects (46.4% versus 9.1%), and improvement in mental health (16.0% versus 4.9%), compared with dermatologists. Although patient-clinician communication was observed to be generally good, 10.9% of patients reported dissatisfaction with communication in AD management. The majority of patients were either "very satisfied" or "satisfied" with their latest acute AD treatment, but 65.5% of patients still desired additional treatment. CONCLUSIONS: This multinational study has provided insights on the perspectives of Asian patients and dermatologists in treatment goals, AD management, and communication. In general, both patients and dermatologists were aligned in treatment goals and there was satisfactory patient-clinician communication in most aspects. However, potential areas of improvement have been identified to further enhance patient-centered care.

5.
Zhongguo Zhong Yao Za Zhi ; 49(12): 3280-3287, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-39041090

ABSTRACT

Based on the insulin receptor substrate(IRS)/phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt) pathway, the intervention effect of Yupingfeng Powder on type 2 diabetes mellitus(T2DM) rats was studied, and the potential mechanism of improving T2DM hepatic insulin resistance was explored. A T2DM rat model was established by feeding with high-fat and high-sugar feed combined with intraperitoneal injection of streptozotocin. Successfully modeled rats were selected and divided into a model group, a positive control group(MET), and a Yupingfeng Powder group. At the same time, a blank group was set up, and corresponding drugs were given by gavage. The model group and blank group were given an equal amount of physiological saline by gavage. During the experiment, body mass and fasting blood glucose were regularly measured, and glucose tolerance and insulin tolerance were measured at the end of the experiment. After the experiment, the levels of blood glucose, insulin, blood lipids, and related liver function indicators were measured; changes in liver pathological damage were observed, levels of liver monoamine oxidase were detected, and qRT-PCR was used to detect mRNA expression levels of IRS/PI3K/Akt pathway related genes. Compared with the model group, the Yupingfeng Powder group had an increase in body weight, a decrease in fasting blood glucose, fasting insulin, and steady-state model evaluation index, a decrease in the area under the curve of glucose tolerance and insulin tolerance tests, a decrease in serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol content, and an increase in high-density lipoprotein cholesterol content. Compared with the model group, the Yupingfeng Powder group showed a decrease in liver monoamine oxidase levels, a decrease in serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin levels, and an increase in total protein and albumin levels. Hematoxylin-eosin(HE) staining showed a reduction in pathological liver cell damage. Compared with the model group, the Yupingfeng Powder group showed a significant increase in the mRNA expression levels of IRS1, PI3K, and Akt in the liver of rats, as well as a significant decrease in the mRNA expression levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α). This indicates that Yupingfeng Powder can regulate the IRS/PI3K/Akt signaling pathway and glucose and lipid metabolism disorders, increase insulin sensitivity, improve hepatic insulin resistance, and thus play a therapeutic role in T2DM.


Subject(s)
Diabetes Mellitus, Type 2 , Drugs, Chinese Herbal , Insulin Receptor Substrate Proteins , Insulin Resistance , Liver , Phosphatidylinositol 3-Kinases , Powders , Proto-Oncogene Proteins c-akt , Signal Transduction , Animals , Rats , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/genetics , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , Liver/metabolism , Liver/drug effects , Male , Insulin Receptor Substrate Proteins/metabolism , Insulin Receptor Substrate Proteins/genetics , Signal Transduction/drug effects , Rats, Sprague-Dawley , Blood Glucose/metabolism , Insulin/metabolism , Humans
6.
Bioorg Chem ; 147: 107387, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38643561

ABSTRACT

Histamine 4 receptor (H4R), the most recently identified subtype of histamine receptor, primarily induces inflammatory reactions upon activation. Several H4R antagonists have been developed for the treatment of inflammatory bowel disease (IBD) and atopic dermatitis (AD), but their use has been limited by adverse side effects, such as a short half-life and toxicity. Natural products, as an important source of anti-inflammatory agents, offer minimal side effects and reduced toxicity. This work aimed to identify novel H4R antagonists from natural products. An H4R target-pathway model deconvoluted downstream Gi and MAPK signaling pathways was established utilizing cellular label-free integrative pharmacology (CLIP), on which 148 natural products were screened. Cryptotanshinone was identified as selective H4R antagonist, with an IC50 value of 11.68 ± 1.30 µM, which was verified with Fluorescence Imaging Plate Reader (FLIPR) and Cellular Thermal Shift (CTS) assays. The kinetic binding profile revealed the noncompetitive antagonistic property of cryptotanshinone. Two allosteric binding sites of H4R were predicted using SiteMap, Fpocket and CavityPlus. Subsequent molecular docking and dynamics simulation indicated that cryptotanshinone interacts with H4R at a pocket formed by the outward interfaces between TM3/4/5, potentially representing a new allosteric binding site for H4R. Overall, this study introduced cryptotanshinone as a novel H4R antagonist, offering promise as a new hit for drug design of H4R antagonist. Additionally, this study provided a novel screening model for the discovery of H4R antagonists.


Subject(s)
Biological Products , Dose-Response Relationship, Drug , Drug Discovery , Receptors, Histamine H4 , Humans , Biological Products/chemistry , Biological Products/pharmacology , Receptors, Histamine H4/antagonists & inhibitors , Receptors, Histamine H4/metabolism , Structure-Activity Relationship , Molecular Structure , Phenanthrenes/pharmacology , Phenanthrenes/chemistry , Histamine Antagonists/pharmacology , Histamine Antagonists/chemistry , Molecular Docking Simulation , Phenotype
7.
Ann Plast Surg ; 92(1S Suppl 1): S12-S20, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38285990

ABSTRACT

ABSTRACT: Adipose-derived stem cells (ADSCs) have become an accepted source of cells in bone tissue engineering. This study aimed to investigate whether platelet-rich plasma (PRP) lysate can replace traditional fetal bovine serum as a culture medium with the enhanced proliferation and osteogenic potential of ADSCs. We divided the experiment into 5 groups where the ADSCs were cultured in an osteogenic medium containing 2.5%, 5%, 7.5%, and 10% PRP lysate with 10% fetal bovine serum as the control group. The cell proliferation, alkaline phosphatase (ALP) activity, ALP stain, alizarin red stain, osteocalcin (OCN) protein expression, and osteogenic-specific gene expression were analyzed and compared among these groups. The outcome showed that all PRP lysate-treated groups had good ALP stain and ALP activity performance. Better alizarin red stains were found in the 2.5%, 5%, and 7.5% PRP lysate groups. The 2.5% and 5% PRP lysate groups showed superior results in OCN quantitative polymerase chain reaction, whereas the 5% and 7.5% PRP lysate groups showed higher OCN protein expressions. Early RUNX2 (Runt-related transcription factor 2 () genes were the most expressed in the 5% PRP lysate group, followed by the 2.5% PRP lysate group, and then the 7.5% PRP lysate group. Thus, we concluded that 5% PRP lysate seemed to provide the optimal effect on enhancing the osteogenic potential of ADSCs. Platelet-rich plasma lysate-treated ADSCs were considered to be a good cell source for application in treating nonunion or bone defects in the future.


Subject(s)
Anthraquinones , Osteogenesis , Platelet-Rich Plasma , Humans , Serum Albumin, Bovine/metabolism , Cells, Cultured , Cell Differentiation , Cell Proliferation , Osteocalcin/genetics , Osteocalcin/metabolism , Platelet-Rich Plasma/metabolism , Stem Cells/metabolism
8.
Hemoglobin ; 48(1): 24-29, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38240123

ABSTRACT

δß-thalassemia is a rare type of thalassemia characterized by increased Hb F levels, including mainly Chinese Gγ(Aγδß)0-thalassemia, Yunnanese Gγ(Aγδß)0-thalassemia, Cantonese Gγ(Aγδß)0-thalassemia in China. Due to the low rate of δß-thalassemia carriers, there are few reports of δß-thalassemia combined with ß-thalassemia causing ß-thalassemia major. Herein, we described the combination of Chinese Gγ(Aγδß)0-thalassemia and ß-thalassemia leading to ß-thalassemia major in a Chinese patient. Hemoglobin analysis was performed by capillary electrophoresis (CE). Routine genetic analysis was carried out by gap-polymerase chain reaction (Gap-PCR) and PCR and reverse dot blot (PCR-RDB). Multiple ligation-dependent probe amplification (MLPA) was used to detect the large deletion, and Gap-PCR confirmed the deletion. A CE result showed an elevated Hb F level of 98.7% and 11.7% in the proband and her mother, but the proband was diagnosed with ßCD17M/ßCD17M using routine genetic analysis. However, her father was heterozygous for CD17 in ß-globin, and her mother was detected as SEA heterozygous. The further analysis presented that the proband had actually missed the diagnosis of Chinese Gγ(Aγδß)0-thalassemia by MLPA and PCR-RDB. Finally, the genotype of the proband was corrected from ßCD17M/ßCD17M to ßCD17M/ßGγ(Aγδß)0. This is the first report of Chinese Gγ(Aγδß)0-thalassemia combined with ß-thalassemia resulting in ß-thalassemia major in China. Screening for δß-thalassemia by Hb analysis could be an effective method.


Subject(s)
Thalassemia , beta-Thalassemia , Female , Humans , beta-Thalassemia/complications , beta-Thalassemia/diagnosis , beta-Thalassemia/genetics , Fetal Hemoglobin/genetics , Thalassemia/genetics , Hemoglobins/genetics , Diagnostic Errors
9.
Seizure ; 116: 4-13, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37777370

ABSTRACT

PURPOSE: To provide an updated list of epilepsy-associated genes based on clinical-genetic evidence. METHODS: Epilepsy-associated genes were systematically searched and cross-checked from the OMIM, HGMD, and PubMed databases up to July 2023. To facilitate the reference for the epilepsy-associated genes that are potentially common in clinical practice, the epilepsy-associated genes were ranked by the mutation number in the HGMD database and by case number in the China Epilepsy Gene 1.0 project, which targeted common epilepsy. RESULTS: Based on the OMIM database, 1506 genes were identified to be associated with epilepsy and were classified into three categories according to their potential association with epilepsy or other abnormal phenotypes, including 168 epilepsy genes that were associated with epilepsies as pure or core symptoms, 364 genes that were associated with neurodevelopmental disorders as the main symptom and epilepsy, and 974 epilepsy-related genes that were associated with gross physical/systemic abnormalities accompanied by epilepsy/seizures. Among the epilepsy genes, 115 genes (68.5%) were associated with epileptic encephalopathy. After cross-checking with the HGMD and PubMed databases, an additional 1440 genes were listed as potential epilepsy-associated genes, of which 278 genes have been repeatedly identified variants in patients with epilepsy. The top 100 frequently reported/identified epilepsy-associated genes from the HGMD database and the China Epilepsy Gene 1.0 project were listed, among which 40 genes were identical in both sources. SIGNIFICANCE: Recognition of epilepsy-associated genes will facilitate genetic screening strategies and be helpful for precise molecular diagnosis and treatment of epilepsy in clinical practice.


Subject(s)
Epilepsy , Humans , Epilepsy/genetics , Seizures/genetics , Genetic Testing , Mutation/genetics , Databases, Factual , Phenotype
10.
Cell Signal ; 113: 110943, 2024 01.
Article in English | MEDLINE | ID: mdl-37890687

ABSTRACT

Long non-coding RNAs (lncRNAs) have been shown to drive cancer progression. However, the function of lncRNAs and the underlying mechanism in early-stage breast cancer(BC) have rarely been investigated. Datasets of pre-invasive ductal carcinoma in situ (DCIS), invasive ductal BC (IDC) and normal breast tissue from TCGA and GEO databases were used to conduct bioinformatics analysis. LncRNA CARMN was identified as a tumor suppressor in early-stage BC and related to a better prognosis. CARMN over-expression inhibited MMP2 mediated migration and EMT in BC. Further analysis showed that CARMN was located in the nucleus and functioned as an enhancer RNA (eRNA) in mammary epithelial cell. Mechanically, CARMN binding protein DHX9 was identified by RNA pull-down and mass spectrometry (MS) assays and it also bound to the MMP2 promoter to activate its transcription. As a decoy, CARMN competitively bound to DHX9 and blocked MMP2 transcriptional activation, thereby inhibiting metastasis and EMT of BC cells. These findings reveal the important role of CARMN as a tumor suppressor in the metastasis and a potential biomarker for progression in early-stage BC.


Subject(s)
Breast Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , Female , Breast Neoplasms/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Matrix Metalloproteinase 2/metabolism , Epithelial-Mesenchymal Transition/genetics , Epithelial Cells/metabolism , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , MicroRNAs/genetics , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , DEAD-box RNA Helicases/genetics , DEAD-box RNA Helicases/metabolism
11.
Cancer Cell ; 41(12): 2038-2050.e5, 2023 12 11.
Article in English | MEDLINE | ID: mdl-38039962

ABSTRACT

Esophageal squamous cell carcinoma (ESCC) develops through a series of increasingly abnormal precancerous lesions. Previous studies have revealed the striking differences between normal esophageal epithelium and ESCC in copy number alterations (CNAs) and mutations in genes driving clonal expansion. However, due to limited data on early precancerous lesions, the timing of these transitions and which among them are prerequisites for malignant transformation remained unclear. Here, we analyze 1,275 micro-biopsies from normal esophagus, early and late precancerous lesions, and esophageal cancers to decipher the genomic alterations at each stage. We show that the frequency of TP53 biallelic inactivation increases dramatically in early precancerous lesion stage while CNAs and APOBEC mutagenesis substantially increase at late stages. TP53 biallelic loss is the prerequisite for the development of CNAs of genes in cell cycle, DNA repair, and apoptosis pathways, suggesting it might be one of the earliest steps initiating malignant transformation.


Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Precancerous Conditions , Humans , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Genomics , Precancerous Conditions/genetics , Precancerous Conditions/pathology
12.
Int J Biol Macromol ; 253(Pt 1): 126528, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37633562

ABSTRACT

In this study, we fabricate squeezable cryogel microbeads as injectable scaffolds for minimum invasive delivery of chondrocytes for cartilage tissue engineering applications. The microbeads with different glucosamine concentrations were prepared by combining the water-in-oil emulsion and cryogelation through crosslinking of gelatin with glutaraldehyde in the presence of glucosamine. The physicochemical characterization results show the successful preparation of cryogel microbeads with uniform shape and size, high porosity, large pore size, high water uptake capacity, and good injectability. In vitro analysis indicates proliferation, migration, and differentiated phenotype of rabbit chondrocytes in the cryogel scaffolds. The seeded chondrocytes in the cryogel scaffold can be delivered by injecting through an 18G needle to fully retain the cell viability. Furthermore, the incorporation of glucosamine in the cryogel promoted the differentiated phenotype of chondrocytes in a dose-dependent manner, from cartilage-specific gene expression and protein production. The in vivo study by injecting the cryogel microbeads into the subcutaneous pockets of nude mice indicates good retention ability as well as good biocompatibility and suitable biodegradability of the cryogel scaffold. Furthermore, the injected chondrocyte/cryogel microbead constructs can form ectopic functional neocartilage tissues following subcutaneous implantation in 21 days, as evidenced by histological and immunohistochemical analysis.


Subject(s)
Cartilage, Articular , Tissue Engineering , Animals , Mice , Rabbits , Tissue Engineering/methods , Chondrocytes/metabolism , Cryogels/chemistry , Tissue Scaffolds/chemistry , Microspheres , Gelatin/chemistry , Glucosamine/metabolism , Mice, Nude , Water/metabolism
13.
Breast Cancer Res ; 25(1): 75, 2023 06 26.
Article in English | MEDLINE | ID: mdl-37365643

ABSTRACT

BACKGROUND: DNA damage and DNA damage repair (DDR) are important therapeutic targets for triple-negative breast cancer (TNBC), a subtype with limited chemotherapy efficiency and poor outcome. However, the role of microRNAs in the therapy is emerging. In this study, we explored whether miR-26a-5p could act as BRCAness and enhance chemotherapy sensitivity in TNBC. METHODS: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-26a-5p in breast cancer tissues and cell lines. CCK-8 was used to measure drug sensitivity in concentration gradient and time gradient. Comet assay was used to detect DNA damage. Flow cytometry was performed to examine apoptosis. Moreover, we used western blot and immunofluorescence to detect biomarkers. Luciferase reporter assay was performed to verify the combination of miR-26a-5p and 3'UTR of target gene. Hormone deprivation and stimulation assay were used to validate the effect of hormone receptors on the expression of miR-26a-5p. Chromatin immunoprecipitation (ChIP) assays were used to verify the binding sites of ER-a or PR with the promoter of miR-26a-5p. Animal experiments were performed to the effect of miR-26a-5p on Cisplatin treatment. RESULTS: The expression of miR-26a-5p was significantly downregulated in TNBC. Overexpressing miR-26a-5p enhanced the Cisplatin-induced DNA damage and following apoptosis. Interestingly, miR-26a-5p promoted the expression of Fas without Cisplatin stimulating. It suggested that miR-26a-5p provided a hypersensitivity state of death receptor apoptosis and promoted the Cisplatin sensitivity of TNBC cells in vitro and in vivo. Besides, miR-26a-5p negatively regulated the expression of BARD1 and NABP1 and resulted in homologous recombination repair defect (HRD). Notably, overexpressing miR-26a-5p not only facilitated the Olaparib sensitivity of TNBC cells but also the combination of Cisplatin and Olaparib. Furthermore, hormone receptors functioned as transcription factors in the expression of miR-26a-5p, which explained the reasons that miR-26a-5p expressed lowest in TNBC. CONCLUSIONS: Taken together, we reveal the important role of miR-26a-5p in Cisplatin sensitivity and highlight its new mechanism in DNA damage and synthetic lethal.


Subject(s)
MicroRNAs , Triple Negative Breast Neoplasms , Humans , Animals , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/metabolism , Cisplatin/pharmacology , Cisplatin/therapeutic use , Cell Line, Tumor , Cell Proliferation/genetics , MicroRNAs/genetics , Carrier Proteins , Hormones
14.
Opt Express ; 31(9): 14308-14316, 2023 Apr 24.
Article in English | MEDLINE | ID: mdl-37157298

ABSTRACT

A 32×32 100 GHz silicon photonic integrated arrayed waveguide grating router (AWGR) is experimentally demonstrated for dense wavelength division multiplexing (DWDM) applications. The dimension of the AWGR is 2.57 mm×1.09 mm with a core size of 1.31 mm×0.64 mm. It exhibits 6.07 dB maximum channel loss non-uniformity with -1.66 dB best-case insertion loss and average channel crosstalk of -15.74 dB. In addition, in the case of 25 Gb/s signals, the device successfully realizes high-speed data routing. The AWG router provides clear optical eye diagrams and low power penalty at bit-error-rates of 10-9.

15.
Appl Opt ; 62(7): 1662-1666, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-37132910

ABSTRACT

Photonic antennas are critical in applications such as spectroscopy, photovoltaics, optical communications, holography, and sensors. Metal antennas are widely used because of their small size, but they are difficult to be compatible with a CMOS. All-dielectric antennas are easier to integrate with Si waveguides, but are generally larger in size. In this paper, we propose the design of a small-sized, high-efficiency semicircular dielectric grating antenna. The antenna's key size is only 2.37µm×4.74µm, and the emission efficiency reaches over 64% in the wavelength range from 1.16 to 1.61 µm. The antenna provides a new, to the best of our knowledge, approach for three-dimensional optical interconnections between different decks of integrated photonic circuits.

16.
J Plast Reconstr Aesthet Surg ; 82: 12-20, 2023 07.
Article in English | MEDLINE | ID: mdl-37148805

ABSTRACT

BACKGROUND: Craniofacial bones are the most commonly involved site of Langerhans cell histiocytosis (LCH). The main purpose of this study was to clarify the relation between subsites of craniofacial bone and clinical presentation, treatment modalities, outcomes, and permanent consequences (PCs) in patients with LCH. METHODS: Forty-four patients diagnosed with LCH involving the craniofacial region presenting at a single medical center during 2001-2019 were collected and divided into four groups: single system with unifocal bone lesion (SS-LCH, UFB); single system with multifocal bone lesions (SS-LCH, MFB); multisystem without risk organ involvement (MS-LCH, RO-); and multisystem with risk organ involvement (MS-LCH, RO+). Data including demographics, clinical presentation, treatments, outcomes, and the development of PC were retrospectively reviewed. RESULTS: Temporal bone (66.7% versus 7.7%, p = 0.001), occipital bone (44.4% versus 7.7%, p = 0.022), and sphenoid bone (33.3% versus 3.8%, p = 0.041) involvement were more common in SS-LCH, MFB than they were in SS-LCH, UFB. No difference of reactivation rate was noted among the four groups. The most common PC is diabetes insipidus (DI), reported in 9 of the 16 (56.25%) patients with PC. The single system group was reported with the lowest incidence of DI (7.7%, p = 0.035). The reactivation rate was also higher in patients with PC (33.3% versus 4.0%, p = 0.021) or DI (62.5% versus 3.1%, p < 0.001). CONCLUSION: An increased risk of multifocal or multisystem lesions was associated with temporal bone, occipital bone, sphenoid bone, maxillary bone, eye, ear, and oral involvement, which may indicate poor outcomes. Longer follow-up may be indicated if there is the presence of PC or DI due to the high risk of reactivation. Therefore, multidisciplinary evaluation and treatment according to risk stratification are vital for patients diagnosed with LCH involving the craniofacial region.


Subject(s)
Histiocytosis, Langerhans-Cell , Humans , Retrospective Studies , Histiocytosis, Langerhans-Cell/therapy , Histiocytosis, Langerhans-Cell/complications , Histiocytosis, Langerhans-Cell/diagnosis , Temporal Bone
17.
Ann Plast Surg ; 90(1 Suppl 1): S19-S25, 2023 04 01.
Article in English | MEDLINE | ID: mdl-37075291

ABSTRACT

BACKGROUND: The treatment strategies for mandibular condylar head fractures, also known as intracapsular condylar fractures (ICFs), have not been concluded. We humbly present our treatment outcomes and share our experience in our department. AIMS AND OBJECTIVES: The aim of this study was to compare the functional outcomes between closed reduction (CR) and open reduction and internal fixation (ORIF) for management of unilateral or bilateral ICFs. MATERIALS AND METHODS: This 10-year retrospective cohort study included 71 patients with 102 ICFs who were treated in our department from May 2007 to August 2017. Nine patients mixed with extracapsular fractures were excluded; thus, 62 patients with 93 ICFs were included. All patients received treatment by the senior surgeon in Chang Gung Memorial Hospital, Linkou Branch, Taiwan. The patient's basic data, fracture morphologies, associated injuries, managements, complications, and maximal mouth opening (MMO) measurement at 1, 3, 6, and 12 months postoperative were reviewed for analysis. RESULTS: Among the 93 fractures, 31 (50%) were bilateral and 31 were unilateral (50%). Based on He's classification, 45 (48%) had type A fracture, 13 (14%) had type B, 5 (5%) had type C, 20 (22%) had type M, and 10 (11%) had no displacement. Maximal mouth opening of 37 mm in unilateral cases after 6 months was significantly higher than the 33-mm MMO in bilateral cases. In addition, the MMO in the ORIF group was significantly higher than that of the CR group in 3 months postoperative. Univariate (odds ratio, 4.92; P = 0.01) and multivariate (odds ratio, 4.76; P = 0.027) analyses revealed CR as an independent risk factor for trismus development compared with ORIF. Malocclusion was observed in 5 patients in both CR and ORIF groups. In addition, 1 patient developed temporomandibular joint osteoarthritis in the CR group. No surgical-related temporary or permanent facial nerve palsy was observed. CONCLUSIONS: Open reduction and internal fixation for condylar head fracture provided better recovery in MMO than CR, and the MMO recovery was less in bilateral condylar head fracture than unilateral condylar head fracture. Open reduction and internal fixation in ICFs have a lower risk for trismus development and should be the treatment of choice in selected cases.


Subject(s)
Mandibular Fractures , Trismus , Male , Humans , Retrospective Studies , Mandibular Fractures/surgery , Temporomandibular Joint/injuries , Temporomandibular Joint/surgery , Mandibular Condyle/surgery , Mandibular Condyle/injuries , Treatment Outcome , Fracture Fixation, Internal
18.
Appl Opt ; 62(5): 1279-1284, 2023 Feb 10.
Article in English | MEDLINE | ID: mdl-36821228

ABSTRACT

We propose a compact, ultrabroadband and temperature-insensitive adiabatic directional coupler based on rib silicon waveguide-enabling arbitrary splitting ratios. Simulation results show that the device can achieve arbitrary splitting ratios from 1400 to 1600 nm, equal to 50%:50%, 60%:40%, 70%:30%, 80%:20%, and 90%:10% for the fundamental transverse electric mode. The designed device has an excess loss of less than 0.19 dB on the operational waveband. Furthermore, the proposed device shows a great robustness to fabrication imperfection, with a waveguide width deviation of 50 nm and ambient temperature change from 0°C to 200°C. These properties make the design a potential candidate for ultrahigh-density photonic integration chips.

19.
Ann Plast Surg ; 90(1 Suppl 1): S26-S31, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36752414

ABSTRACT

BACKGROUND: Motorcycle injuries remain a significant cause of motor vehicle-related morbidity and mortality in Taiwan. Besides, the facial region is a commonly fractured site under motorcycle accidents. To date, there are no trauma mechanism-based studies of facial fractures. AIM AND OBJECTIVES: This study aims to determine the facial fracture patterns, the severity of head trauma, and associated injuries by different motorcycle-related trauma mechanisms enabling a greater understanding of its distribution and magnitude. METHODS: This is a retrospective descriptive analysis conducted over a 2-year period at Linkou Chang Gung Memorial Hospital. We focused on the population of maxillofacial injury caused by motorcycle accidents. We divided the patient cohort into 3 main trauma mechanisms: single-motorcycle collision (SM group), motorcycle-to-motorcycle collision (MM group), motorcycle-to-vehicle collision (MV group). Data, including demographics, age, fracture patterns of facial bones, and other associated injuries, were collected. RESULTS: A total of 881 cases were identified that involved facial fractures. Most patients were male (71%), young adult (mean age, 32.49 years), and the most common fracture region is the midfacial fracture (79.5%, 700 victims). Among the 3 groups, the MM group was less likely to sustain severe injuries by trauma score system, less head injury and mortality rate. The MV group and SM group have similar mortality rates but different fracture pattern tendencies. Lower facial fractures were more likely in the MV group, but midface fractures in the SM group. Associated injuries were higher in the MV group. CONCLUSIONS: Our study presents the different trends of fracture patterns and injury under 3 main mechanisms of motorcycle casualties. We document all these data in the hope of providing insights into trauma doctors dealing with motorcycle accidents.


Subject(s)
Craniocerebral Trauma , Facial Injuries , Skull Fractures , Young Adult , Humans , Male , Adult , Female , Retrospective Studies , Motorcycles , Accidents, Traffic , Skull Fractures/epidemiology , Skull Fractures/etiology , Facial Injuries/epidemiology , Facial Injuries/etiology , Facial Bones
20.
Ann Plast Surg ; 90(1 Suppl 1): S2-S9, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36752416

ABSTRACT

BACKGROUND: LeFort I osteotomy changes the morphology of the nose. The cinch suture has been proven to prevent the increase in nasal base and alar width. Different types of cinch sutures have been proposed. However, their effectiveness is unclear. AIM AND OBJECTIVES: The aim of this study was to compare the surgical outcomes between conventional and modified cinch techniques through a systematic review and meta-analysis of randomized control trials (RCTs). MATERIAL AND METHODS: We performed systematic search from Embase, PubMed, and the Cochrane Library according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement up to March 2021. The surgical techniques of different cinch sutures were reviewed, and the outcomes of nasal alar width and alar base width were compared between modified and conventional methods. RESULTS: A total of 4 eligible RCTs were included in this meta-analysis. Pooled data showed no significant difference in alar base width change between modified and conventional methods (mean difference, -0.37; 95% confidence interval, -1.32 to 0.57; P = 0.44). Pooled data of 3 studies also showed no significant difference in nasal alar width change (mean difference, -0.11; 95% confidence interval, -1.18 to 0.95; P = 0.83). CONCLUSION: Based on the current data pooled from the available RCTs, no significant difference was found between the conventional cinch technique and the modified technique.


Subject(s)
Maxilla , Nasal Cartilages , Humans , Nasal Cartilages/surgery , Maxilla/surgery , Osteotomy, Le Fort/methods , Nose/surgery , Suture Techniques
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