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2.
Int J Biol Macromol ; 264(Pt 1): 130542, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38432272

ABSTRACT

Pathological cardiac hypertrophy (CH) is driven by maladaptive changes in myocardial cells in response to pressure overload or other stimuli. CH has been identified as a significant risk factor for the development of various cardiovascular diseases, ultimately resulting in heart failure. Melanoma differentiation-associated protein 5 (MDA5), encoded by interferon-induced with helicase C domain 1 (IFIH1), is a cytoplasmic sensor that primarily functions as a detector of double-stranded ribonucleic acid (dsRNA) viruses in innate immune responses; however, its role in CH pathogenesis remains unclear. Thus, the aim of this study was to examine the relationship between MDA5 and CH using cellular and animal models generated by stimulating neonatal rat cardiomyocytes with phenylephrine and by performing transverse aortic constriction on mice, respectively. MDA5 expression was upregulated in all models. MDA5 deficiency exacerbated myocardial pachynsis, fibrosis, and inflammation in vivo, whereas its overexpression hindered CH development in vitro. In terms of the underlying molecular mechanism, MDA5 inhibited CH development by promoting apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, thereby suppressing c-Jun N-terminal kinase/p38 signaling pathway activation. Rescue experiments using an ASK1 activation inhibitor confirmed that ASK1 phosphorylation was essential for MDA5-mediated cell death. Thus, MDA5 protects against CH and is a potential therapeutic target.


Subject(s)
Apoptosis , MAP Kinase Kinase Kinase 5 , Mice , Rats , Animals , Interferon-Induced Helicase, IFIH1/genetics , Interferon-Induced Helicase, IFIH1/metabolism , MAP Kinase Kinase Kinase 5/metabolism , Apoptosis/physiology , Cardiomegaly/metabolism , Signal Transduction , JNK Mitogen-Activated Protein Kinases/metabolism
3.
Sci Data ; 11(1): 218, 2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38368451

ABSTRACT

As an important forestry pest, Coronaproctus castanopsis (Monophlebidae) has caused serious damage to the globally valuable Gutianshan ecosystem, China. In this study, we assembled the first chromosome-level genome of the female specimen of C. castanopsis by merging BGI reads, HiFi long reads and Hi-C data. The assembled genome size is 700.81 Mb, with a scaffold N50 size of 273.84 Mb and a contig N50 size of 12.37 Mb. Hi-C scaffolding assigned 98.32% (689.03 Mb) of C. Castanopsis genome to three chromosomes. The BUSCO analysis (n = 1,367) showed a completeness of 91.2%, comprising 89.2% of single-copy BUSCOs and 2.0% of multicopy BUSCOs. The mapping ratio of BGI, second-generation RNA, third-generation RNA and HiFi reads are 97.84%, 96.15%, 97.96%, and 99.33%, respectively. We also identified 64.97% (455.3 Mb) repetitive elements, 1,373 non-coding RNAs and 10,542 protein-coding genes. This study assembled a high-quality genome of C. castanopsis, which accumulated valuable molecular data for scale insects.


Subject(s)
Forestry , Genome, Insect , Hemiptera , Female , Chromosomes , Ecosystem , Phylogeny , RNA , Hemiptera/genetics
4.
Lancet Oncol ; 25(1): 76-85, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38048802

ABSTRACT

BACKGROUND: Locally advanced cervical cancer constitutes around 37% of cervical cancer cases globally and has a poor prognosis due to limited therapeutic options. Immune checkpoint inhibitors in the neoadjuvant setting could address these challenges. We aimed to investigate the efficacy and safety of neoadjuvant chemo-immunotherapy for locally advanced cervical cancer. METHODS: In this single-arm, phase 2 trial, which was done across eight tertiary hospitals in China, we enrolled patients aged 18-70 years with untreated cervical cancer (IB3, IIA2, or IIB/IIIC1r with a tumour diameter ≥4 cm [International Federation of Gynecology and Obstetrics, 2018]) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients underwent one cycle of priming doublet chemotherapy (75-80 mg/m2 cisplatin, intravenously, plus 260 mg/m2 nab-paclitaxel, intravenously), followed by two cycles of a combination of chemotherapy (cisplatin plus nab-paclitaxel) on day 1 with camrelizumab (200 mg, intravenously) on day 2, with a 3-week interval between treatment cycles. Patients with stable disease or progressive disease received concurrent chemoradiotherapy, and patients with a complete response or partial response proceeded to radical surgery. The primary endpoint was the objective response rate, by independent central reviewer according to Response Evaluation Criteria in Solid Tumours, version 1.1. Activity and safety were analysed in patients who received at least one dose of camrelizumab. This study is registered with ClinicalTrials.gov, NCT04516616, and is ongoing. FINDINGS: Between Dec 1, 2020, and Feb 10, 2023, 85 patients were enrolled and all received at least one dose of camrelizumab. Median age was 51 years (IQR 46-57) and no data on race or ethnicity were collected. At data cutoff (April 30, 2023), median follow-up was 11·0 months (IQR 6·0-14·5). An objective response was noted in 83 (98% [95% CI 92-100]) patients, including 16 (19%) patients who had a complete response and 67 (79%) who had a partial response. The most common grade 3-4 treatment-related adverse events during neoadjuvant chemo-immunotherapy were lymphopenia (21 [25%] of 85), neutropenia (ten [12%]), and leukopenia (seven [8%]). No serious adverse events or treatment-related deaths occurred. INTERPRETATION: Neoadjuvant chemo-immunotherapy showed promising antitumour activity and a manageable adverse event profile in patients with locally advanced cervical cancer. The combination of neoadjuvant chemo-immunotherapy with radical surgery holds potential as a novel therapeutic approach for locally advanced cervical cancer. FUNDING: National Key Technology Research and Development Program of China and the National Clinical Research Center of Obstetrics and Gynecology.


Subject(s)
Thrombocytopenia , Uterine Cervical Neoplasms , Female , Humans , Middle Aged , Cisplatin/adverse effects , Neoadjuvant Therapy/adverse effects , Uterine Cervical Neoplasms/drug therapy , Antibodies, Monoclonal, Humanized/adverse effects , Thrombocytopenia/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects
5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013567

ABSTRACT

Objective To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. Methods Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson’s trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. Results Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson’s trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/μm2 and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/μm2 and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). Conclusions E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.

6.
Chinese Journal of Pathology ; (12): 64-70, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1012426

ABSTRACT

Objective: To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of SRF-rearranged cellular perivascular myoid tumor. Methods: Two cases of SRF-rearranged cellular perivascular myoid tumor diagnosed in the Department of Pathology, Fudan University Shanghai Cancer Center from October 2021 to March 2022 were collected. Immunohistochemical staining, fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS) were performed, and the literature was reviewed. Results: Case 1, a 3-month-old boy presented with a painless tumor of the scalp, measuring about 2 cm in diameter. Case 2, a 3-year-old girl complained with a painless tumor of the knee, measuring approximately 1.5 cm in diameter. Microscopically, the tumor had a clear boundary and showed multinodular growth. The tumor was mainly composed of spindle cells arranged in long intersecting fascicles associated with thin, slit-like or branching ectatic vessels, focally forming hemangiopericytoma-like appearance. The tumor cells were abundant, but there was no obvious atypia. Mitotic figures (3-4/10 HPF) were noted. H-caldesmon and SMA were positive in both cases. Case 1 showed diffuse and strong positivity for Desmin, and focally for CKpan. Ki-67 proliferation index was 20% and 30%, respectively. FISH displayed NCOA2 gene translocation in case 1 and the RELA gene translocation in case 2. NGS detected the SRF-NCOA2 gene fusion in case 1 and the SRF-RELA gene fusion in case 2. Both patients underwent local excisions. During the follow-up of 5-14 months, case 1 had no local recurrence, while case 2 developed local recurrence 1 year post operatively. Conclusions: SRF-rearranged cellular perivascular myoid tumor is a novel variant of perivascular cell tumor, which tends to occur in children and adolescents. The tumor forms a broad morphologic spectrum ranging from a pericytic pattern to a myoid pattern, and include hybrid tumors with a mixture of pericytic and myoid patterns. Due to its diffuse hypercellularity and increased mitotic figures and smooth muscle-like immunophenotype, the tumor is easy to be misdiagnosed as myogenic sarcomas. The tumor usually pursues a benign clinical course and rare cases may locally recur.


Subject(s)
Child, Preschool , Female , Humans , Infant , Male , Biomarkers, Tumor/analysis , Calmodulin-Binding Proteins , China , Hemangiopericytoma/pathology , Sarcoma/pathology , Soft Tissue Neoplasms/pathology
7.
International Eye Science ; (12): 255-259, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1005391

ABSTRACT

Swept-source optical coherence tomography angiography(SS-OCTA)is a new vascular imaging technique that was recently proposed. It has the advantages of being non-invasive, quick, high-resolution, and automated vascular stratification imaging. It is extremely helpful in the early diagnosis of ophthalmology-related diseases, as well as in the evaluation of treatment effectiveness and the tracking of disease progression. Based on the foundation of OCTA, SS-OCTA utilizes a fast-tuning laser with a wavelength of 1 050 nm for deeper penetration and non-invasive depth-resolved imaging of the retinal and choroidal microvascular systems, deepening the understanding of the characteristics of a wide range of ophthalmic diseases(fundus lesions, glaucoma, neurodegenerative diseases, etc.). The structures of the anterior segment of the eye can also be studied using SS-OCTA, including changes in the depth and density of corneal neovascularization as well as changes in iris neovascularization before and after therapy. This approach provides a novel tool for ophthalmic clinical practice. The development of the clinical use of SS-OCTA technology in ophthalmology is reviewed in this article.

8.
BMC Genom Data ; 24(1): 61, 2023 11 02.
Article in English | MEDLINE | ID: mdl-37919672

ABSTRACT

OBJECTIVES: Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype with limited treatment options. Unlike other breast cancer subtypes, the scarcity of specific therapies and greater frequencies of distant metastases contribute to its aggressiveness. We aimed to find epigenetic changes that aid in the understanding of the dissemination process of these cancers. DATA DESCRIPTION: Using CRISPR/Cas9, our experimental approach led us to identify and disrupt an insulator element, IE8, whose activity seemed relevant for cell invasion. The experiments were performed in two well-established TNBC cellular models, the MDA-MB-231 and the MDA-MB-436. To gain insights into the underlying molecular mechanisms of TNBC invasion ability, we generated and characterized high-resolution chromatin interaction (Hi-C) and chromatin accessibility (ATAC-seq) maps in both cell models and complemented these datasets with gene expression profiling (RNA-seq) in MDA-MB-231, the cell line that showed more significant changes in chromatin accessibility. Altogether, our data provide a comprehensive resource for understanding the spatial organization of the genome in TNBC cells, which may contribute to accelerating the discovery of TNBC-specific alterations triggering advances for this devastating disease.


Subject(s)
Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Chromatin/genetics , Cell Line, Tumor , Gene Expression Profiling , Breast/metabolism , Breast/pathology
9.
BMC Med ; 21(1): 464, 2023 11 27.
Article in English | MEDLINE | ID: mdl-38012705

ABSTRACT

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.


Subject(s)
Nasopharyngeal Neoplasms , Neoplasm Recurrence, Local , Humans , Nasopharyngeal Carcinoma/genetics , Retrospective Studies , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/genetics , Prognosis , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/radiotherapy , Magnetic Resonance Imaging/methods
10.
ACS Appl Mater Interfaces ; 15(40): 47111-47124, 2023 Oct 11.
Article in English | MEDLINE | ID: mdl-37768923

ABSTRACT

Recently, growing interest in self-powered devices has led to the invention of new energy conversion devices. Photo-thermoelectric generators (PTEGs) have rapidly developed for their ability to harvest both light and thermal energy, but these devices are overly dependent on the continuity of energy input and cannot sustain output in an emergency situation. In the current study, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)/graphene oxide (GO)/graphene nanosheets (GNPs)/polyethylene glycol (PEG) phase-change composites (PCCs) were prepared with freeze-drying and vacuum-filling processes to acquire materials suitable for imparting energy storage characteristics to PTEGs. The melting and crystallization enthalpies of the PCCs fabricated based on the PEDOT:PSS/GO/GNP aerogels can reach 211.5 and 207.6 J g-1, respectively, which increase by nearly 5% compared with pure PEG, and the growth rate of thermal conductivity of the composites is as high as 262.7% (1.12 W m-1 K-1). Meanwhile, the excellent photothermal properties and high-temperature shape stability that pure PEG does not possess can also be imparted to PCCs by the aerogels. The PTEG assembled with PCCs and thermoelectric components can achieve a continuous output of over 1500 s after 300 s of light irradiation. After integrating the output of the device during the lamp on/off period, it is found that the total output of the device during the light-off period (8.4 V and 9.6 mW) can far exceed its total output during the light-on period (2.7 V and 4.4 mW). This work provides guidance for modulating the performance of PCCs and giving PTEGs the ability to operate under emergency or extremely harsh conditions and the prepared PTEGs are highly promising for practical use.

11.
Mitochondrial DNA B Resour ; 8(8): 836-840, 2023.
Article in English | MEDLINE | ID: mdl-37554696

ABSTRACT

Duck breed Longshengcui (Anas platyrhynchos Linnaeus, 1758 breed Longshengcui, LSC) is one of the famous native breed of the Guangxi Zhuang Nationality Autonomous Region in China. In this study, we report the complete mitochondrial genome of LSC. The mitogenome (GenBank accession no. MZ895120) has 16,602 bp in length and consisted of the well-known 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and the control region. The phylogenetic analysis showed that LSC and Zhijiang duck have highly similar genetic relationship. These results are helpful for the conservation of genetic resources and phylogeny of this species.

12.
Zootaxa ; 5258(3): 342-350, 2023 Mar 29.
Article in English | MEDLINE | ID: mdl-37044590

ABSTRACT

The malthusi group of Coccophagus Westwood (Hymenoptera: Aphelinidae) is characterized by a densely setose mesoscutellum with the posterior apical pair of setae distinctly longer than others. In the present paper, two new species of the malthusi group are described from China: Coccophagus infuscatus sp. nov. and Coccophagus bandus sp. nov., both reared from species of Coccidae (Hemiptera: Sternorrhyncha). The type specimens are housed in Institute of Zoology, Chinese Academy of Sciences (IZCAS), Beijing, China.


Subject(s)
Hemiptera , Hymenoptera , Animals , China
13.
Langmuir ; 39(10): 3770-3783, 2023 Mar 14.
Article in English | MEDLINE | ID: mdl-36856335

ABSTRACT

The rapid growth of industrialization has resulted in the release of large quantities of pollutants into the environment, especially dyes and heavy metals, which are environmentally hazardous for humans and animals. It is considered as the most promising and environmentally friendly route to develop green materials by using the green modification method, which has no negative impact on the environment. In this work, the green material of polylactic acid (PLA) was used as the substrate material, and a novel modification method of polydopamine (PDA)-assisted polyethyleneimine (PEI) grafting was developed. The electrospun PLA fibers are mainly composed of stereocomplex crystallites, which were achieved via the electrospinning of poly(l-lactic acid) and poly(d-lactic acid). The water-soluble PEI was grafted onto the PDA-modified PLA fibers through the glutaraldehyde-assisted cross-linking reaction. The prepared composite fibers can be degraded, which is environmentally friendly and meets the requirements of sustainable development. The potential application of such PLA composite fibers in wastewater treatment was intensively evaluated. The results show that at appropriate fabrication conditions (PDA concentration of 3 g·L-1 and a PEI molecular weight of 70,000 g·mol-1), the composite fibers exhibit the maximum adsorption capacities of 612 and 398.41 mg·g-1 for methyl orange (MO) and hexavalent chromium [Cr(VI)], respectively. Simultaneously, about 64.79% of Cr(VI) adsorbed on the composite fibers was reduced to Cr(III). The above results show that the PLA composite fibers have a good development prospect in the field of wastewater treatment.

15.
Acta Pharmaceutica Sinica ; (12): 2448-2453, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-999131

ABSTRACT

C17 is an orally available anti-tumor compound inhibiting cancer stem cell (CSC). In this study, a stable, sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established and validated, and was further applied to a pharmacokinetic study in nude mice receiving C17 by gavage. Using propranolol as the internal standard, the plasma samples were pre-treated by precipitation with methanol and analyzed on an Intersil C8-3 column (100 mm × 2.1 mm, 3 μm), and gradient elution was performed with a mobile phase consisting of 0.1% formic acid aqueous and solution mixed up by 90% isopropanol and 10% acetonitrile. The analyte was detected by a triple quadrupole tandem mass spectrometer, and multiple reaction monitoring was employed to select C17 at m/z 439.3/247.1 and propranolol at m/z 260.2/116.2 in the positive ion mode. The calibration curves were linear (r > 0.995) over the range of 5-800 ng·mL-1. The intra- and inter-day precisions and accuracies were 7.42%-13.22% and -8.99%-8.81% respectively. The method was successfully applied to a PK study in nude mice administered with a single oral dose of 50 mg·kg-1 C17, and the PK data were analyzed with non-linear mixed effect model (NONMEM). Two separated absorption peaks were found in the PK curve of C17, and a two-compartment model with two sequential first-order absorption rate was utilized to describe the PK properties of C17, and the model could provide insights into the physiological process and exposure of C17 in nude mice. All animal experiments were in strict accordance with the regulations of the Biomedical Ethics Committee of Peking University.

16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-998983

ABSTRACT

Crohn’s Disease (CD) is a destructive, relapsing and remitting chronic inflammatory bowel disease that usually progresses to irreversible intestinal structural and functional changes, such as intestinal lumen stenosis, fistula formation and perianal lesions, severely affecting the quality of life of patients. This review summarized the research progress on the mechanism, clinical application and safety of upadacitinib in the treatment of CD. Upadacitinib can increase the clinical remission and endoscopic response rates in patients with CD, improve the long-term outcome of CD patients and provide a new idea for the treatment of CD patients by using biological agents.

17.
International Eye Science ; (12): 2031-2034, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-998485

ABSTRACT

AIM: To analyze the relationship between rs128912 single nucleotide polymorphism(SNP)in the promoter region of Toll-like receptor 3(TLR3)gene and cataract in Chinese Han population.METHODS: A total of 263 patients with cataract admitted to our hospital from June 2019 to June 2021 were selected as study group, and 150 patients with lens dislocation were included in control group. Western blotting was used to detect the expression of TLR3 protein in the anterior capsular tissues of lens in the two groups, and direct sequencing method was applied to analyze the polymorphism of rs128912 locus in the promoter region of TLR3 gene. The expression of peripheral blood TLR3 mRNA of patients with different genotypes was detected by real-time quantitative polymerase chain reaction(RT-qPCR).RESULTS: The expression level of TLR3 protein in the anterior capsular tissues in the study group was higher than that in the control group(P&#x003C;0.05). The frequencies of genotypes(AA, AT, TT)at rs128912 locus in the TLR3 gene promoter region in the study group and the control group were in accordance with Hardy-Weinberg genetic equilibrium, and there were differences in the frequencies of genotypes(AA, AT, TT)and frequencies of alleles(A, T)at rs128912 locus in the TLR3 gene promoter region between both groups(P&#x003C;0.05). The relative expression level of peripheral blood TLR3 mRNA in patients with TT genotype in the study group was higher than that in patients with AA or AT genotypes(P&#x003C;0.05).CONCLUSION: The expression of TLR3 protein in anterior capsular tissues of lens of patients with cataract is significantly up-regulated, and rs128912 locus polymorphism in the TLR3 gene promoter region is related to the susceptibility of cataract in Chinese Han population, and people with TT genotype are more prone to cataract.

18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-996821

ABSTRACT

Cathartic colon (CC) is a common and refractory digestive system disease, with the pathogenesis not fully clarified. The effective therapies other than laxatives and surgery remain to be developed for CC. Therefore, establishing the CC animal models that fit the disease characteristics of western medicine and syndrome characteristics of traditional Chinese medicine (TCM) is an important link to promote the research on this disease. The fitting degree of animal models with the latest Chinese and western medical diagnostic criteria is an indicator to assess the effectiveness of the animal models in simulating the disease characteristics of western medicine and syndrome characteristics of TCM. The literature review showed that the model animals, drugs and their dosage forms, doses, administration methods, and modeling period of CC varied in different studies, and the available CC animal models presented different fitting degrees with the disease characteristics of western medicine and syndrome characteristics of TCM. Rats were the preferred animals for the modeling of CC. Rhei Radix et Rhizoma preparations were commonly used for model inducing, which, however, may cause water electrolyte disorders, decreased immunity, and even death of animals at the late stage of modeling. The animals were modeled by gradually increasing the starting dose, while the starting dose and increasing dose varied. The maintenance dose was determined based on 50% of the animals having loose stools, and the end for a cycle was determined as the time when loose stools disappeared in 80% of animals. The modeling always lasted for 2-3 cycles, approximately 2-4 months. The CC models established with Rhei Radix et Rhizoma granules and rhein had high fitting degrees with the disease and syndrome characteristics. In addition, the CC animal models of TCM syndromes were still in the exploration stage. There were only the animal models of four TCM syndromes: liver depression and spleen deficiency, both Qi and Yin deficiency, Qi stagnation and blood stasis, and spleen and kidney deficiency. Efforts should be made to establish the animal models that meet the characteristics of disease of western medicine and syndromes of TCM, so as to facilitate the research on CC mechanism and drug development.

19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-995729

ABSTRACT

Objective:To evaluate the screening efficacy of AI for bone marrow cell morphology.Method:Bone marrow specimens of patients attending the Second Hospital of Hebei Medical University from December 1,2019 to December 21,2020;(1) Selected from one hundred bone marrow specimens, The cases included chronic myeloid cell leukemia ( n=23), myelodysplastic syndrome ( n=4), chronic lymphocytic leukemia ( n=4), multiple myeloma ( n=5), 7 acute leukemia ( n=7), chronic anemia ( n=32), infection ( n=6) and healthy control ( n=15). Including 45 males and 55 females, with age 52(37,66)years old.The bone marrow smear prepared with Wright-Giemsa, The AI analysis system and manual audit were applied to classify 13 types of bone marrow nucleated cell, taking the results of manual audit as the gold standard, comparing the difference between the results of the two methods, using statistical software to draw the confusion matrix, The compliance between the manual audit results and the pre-classification results of the AI analysis system was calculated by the Kappa consistency test method; The consistency analysis between the pre-classification results of AI and those of the manual microscopic examination was performed by the Pearson test; (2)Statistics analyzed the blast cell differential count differences of AI and manual microscopy, to evaluate the clinical application value of AI analysis system, which soured from thirty bone marrow samples of patients diagnosed with MDS and AML. Results:76 630 images of 13 nucleated cells were obtained by AI analysis system; the weighted average experimental diagnostic efficiency parameters of 13 types of bone marrow nucleated cells, are as follows: sensitivity(%)=95.82, specificity(%)=99.19, accuracy(%)=98.89, false positive rate(%)=0.81, false negative rate (%)=4.18; the correlation results, between the pre-classification results of AI and manual microscopic classification results,showed that blast cell, promyelocytes, neutrophilic myelocyte, neutrophilic metamyelocyte, band neutrophil, segmented neutrophi,eosinophil, basophil, polychromatic erythroblast, orthochromatic erythroblast, and lymphocytes have good positive correlation ( r>0.70,all P<0.001), while basophilic erythroblast and monocytes have no obvious correlation ( r=0.32,0.30, all P> 0.001); the count results of the blast cells in bone marrow smears of MDS and AML, got by AI and manual microscopy respectively, showed that the average percentage of blast cells was 8.19% by AI and 8.68% by manual microscopy in MDS, there was no significant difference between the two methods ( P>0.05); the average percentage of blast cells was 48.52% by AI analysis system and 53.77% by manual microscopy in AML, and although there was a significant difference in blast cell count ( P<0.01), coincidence the classification diagnostic criteria for AML (blast cells ≥ 20%). Conclusion:The AI analysis system performed good sensitivity, specificity and accuracy for 13 types of bone marrow nucleated cells, which showed potential application value for the rapid classification and diagnosis of MDS and AML.

20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-978411

ABSTRACT

ObjectiveTo perform visual analysis of the literature in the field of adolescent social isolation in order to provide reference for research on social isolation of Chinese teenagers. MethodsLiterature related to adolescent social isolation was retrieved from the Web of Science core collection database from September 2013 to September 2022. CiteSpace 6.1.R3 software was used to conduct bibliometric analysis on publication volume, publication organization, keyword clustering, keyword salience, and time⁃line map of hot words. ResultsA total of 1 347 related articles were screened out, and the overall number of publications from 2013 showed an upward trend. The largest number of articles came from the United States with 521 (38.68%), and China ranked 6th with 79 (5.86%). The top three institutions were Columbia University in the United States (29 articles), King's College London in the United Kingdom (28 articles) and the University of London in the United Kingdom (27 articles). Research hotspots mainly focused on social isolation, physical and mental health, loneliness, quality of life and comprehensive interventions. ConclusionIn recent years, the problem of adolescent social isolation has attracted continuous attention from foreign scholars. Based on our national conditions, we should conduct relevant screening and preventive assessment for social isolation of special youth groups, so as to conduct early management and intervention.

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