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1.
Infect Med (Beijing) ; 3(2): 100106, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38827562

ABSTRACT

China has been continuously improving its monitoring methods and strategies to address key infectious diseases (KIDs). After the severe acute respiratory syndrome epidemic in 2003, China established a comprehensive reporting system for infectious diseases (IDs) and public health emergencies. The relatively lagging warning thresholds, limited warning information, and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs. Strengthening early monitoring and warning capabilities to enhance the public health system has become a top priority, with increasing demand for early warning thresholds, information, and techniques, thanks to constant innovation and development in molecular biology, bioinformatics, artificial intelligence, and other identification and analysis technologies. A panel of 31 experts has recommended a fourth-generation comprehensive surveillance system targeting KIDs (41 notifiable diseases and emerging IDs). The aim of this surveillance system is to systematically monitor the epidemiology and causal pathogens of KIDs in hosts such as humans, animals, and vectors, along with associated environmental pathogens. By integrating factors influencing epidemic spread and risk assessment, the surveillance system can serve to detect, predict, and provide early warnings for the occurrence, development, variation, and spread of known or novel KIDs. Moreover, we recommend comprehensive ID monitoring based on the fourth-generation surveillance system, along with a data-integrated monitoring and early warning platform and a consortium pathogen detection technology system. This series of considerations is based on systematic and comprehensive monitoring across multiple sectors, dimensions, factors, and pathogens that is supported by data integration and connectivity. This expert consensus will provides an opportunity for collaboration in various fields and relies on interdisciplinary application to enhance comprehensive monitoring, prediction, and early warning capabilities for the next generation of ID surveillance. This expert consensus will serve as a reference for ID prevention and control as well as other related activities.

3.
Chin Med J (Engl) ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725346

ABSTRACT

BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS: The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.

4.
China CDC Wkly ; 6(15): 332-338, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38736992

ABSTRACT

Introduction: The emergence of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineage, BA.2.86, has sparked global public health concerns for its potential heightened transmissibility and immune evasion. Utilizing data from Shenzhen's city-wide wastewater surveillance system, we highlight the presence of the BA.2.86 lineage in Shenzhen. Methods: A mediator probe polymerase chain reaction (PCR) assay was developed to detect the BA.2.86 lineage in wastewater by targeting a specific mutation (Spike: A264D). Between September 19 and December 10, 2023, 781 wastewater samples from 38 wastewater treatment plants (WWTPs) and 9 pump stations in ten districts of Shenzhen were examined. Through multiple short-amplicon sequencing, three positive samples were identified. Results: The BA.2.86 lineage was identified in the wastewater of Futian and Nanshan districts in Shenzhen on December 2, 2023. From December 2 to 10, a total of 21 BA.2.86-positive wastewater samples were found across 6 districts (Futian, Nanshan, Longhua, Baoan, Longgang, and Luohu) in Shenzhen. The weighted average viral load of the BA.2.86 lineage in Shenzhen's wastewater was 43.5 copies/L on December 2, increased to 219.8 copies/L on December 4, and then decreased to approximately 100 copies/L on December 6, 8, and 10. Conclusions: The mediator probe PCR assay, designed for swift detection of low viral concentrations of the BA.2.86 lineage in wastewater samples, shows promise for detecting different SARS-CoV-2 variants. Wastewater surveillance could serve as an early detection system for promptly identifying specific SARS-CoV-2 variants as they emerge.

5.
Eur J Med Res ; 29(1): 247, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38650017

ABSTRACT

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a cutting-edge life-support measure for patients with severe cardiac and pulmonary illnesses. Although there are several systematic reviews (SRs) about ECMO, it remains to be seen how quality they are and how efficacy and safe the information about ECMO they describe is in these SRs. Therefore, performing an overview of available SRs concerning ECMO is crucial. METHODS: We searched four electronic databases from inception to January 2023 to identify SRs with or without meta-analyses. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were used to assess the methodological quality, and evidence quality for SRs, respectively. A bubble plot was used to visually display clinical topics, literature size, number of SRs, evidence quality, and an overall estimate of efficacy. RESULTS: A total of 17 SRs met eligibility criteria, which were combined into 9 different clinical topics. The methodological quality of the included SRs in this mapping was "Critically low" to "Moderate". One of the SRs was high-quality evidence, three on moderate, three on low, and two on very low-quality evidence. The most prevalent study used to evaluate ECMO technology was observational or cohort study with frequently small sample sizes. ECMO has been proven beneficial for severe ARDS and ALI due to the H1N1 influenza infection. For ARDS, ALF or ACLF, and cardiac arrest were concluded to be probably beneficial. For dependent ARDS, ARF, ARF due to the H1N1 influenza pandemic, and cardiac arrest of cardiac origin came to an inconclusive conclusion. There was no evidence for a harmful association between ECMO and the range of clinical topics. CONCLUSIONS: There is limited available evidence for ECMO that large sample, multi-center, and multinational RCTs are needed. Most clinical topics are reported as beneficial or probably beneficial of SRs for ECMO. Evidence mapping is a valuable and reliable methodology to identify and present the existing evidence about therapeutic interventions.


Subject(s)
Extracorporeal Membrane Oxygenation , Extracorporeal Membrane Oxygenation/methods , Extracorporeal Membrane Oxygenation/adverse effects , Humans , Adult , Systematic Reviews as Topic
6.
Electrophoresis ; 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38577828

ABSTRACT

Capillary electrophoresis (CE) interfaced to mass spectrometry (MS) with electrospray ionization typically incorporates acidic additives or organic solvents to assist in ionization. Vibrating sharp-edge spray ionization (VSSI) is a voltage-free method to interface CE and MS that does not require these additives, making it appealing for protein analyses. CE-VSSI nanoflow sheath separations are performed with low ionic strength aqueous solutions in the sheath to reduce suppression. Serine is also included in the sheath to reduce analyte adduction. Proteins are detected in the 2.5-10 µM range, corresponding to an injected mass range of 0.1-1.2 ng. The anionic proteins ß-lactoglobulin and transferrin are resolved using an unmodified fused silica capillary because they do not exhibit nonspecific surface adsorption. Conversely, separations of cationic proteins cytochrome c, ribonuclease A, and α-chymotrypsinogen A in an unmodified capillary require acidic background electrolytes to overcome adsorption. Alternatively, a semipermanent coating comprised self-assembled lipids overcomes surface adsorption at a neutral pH. Separations with zwitterionic and hybrid cationic coatings are complete within 15 or 6 min, respectively. The dimeric form of triosephosphate isomerase was observed at a 60 µM, corresponding to a mass of 19 ng, by dropping the temperature of the MS inlet.

7.
Infect Immun ; 92(5): e0011324, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38624215

ABSTRACT

Malaria, one of the major infectious diseases in the world, is caused by the Plasmodium parasite. Plasmodium antigens could modulate the inflammatory response by binding to macrophage membrane receptors. As an export protein on the infected erythrocyte membrane, Plasmodium surface-related antigen (SRA) participates in the erythrocyte invasion and regulates the immune response of the host. This study found that the F2 segment of P. yoelii SRA activated downstream MAPK and NF-κB signaling pathways by binding to CD68 on the surface of the macrophage membrane and regulating the inflammatory response. The anti-PySRA-F2 antibody can protect mice against P. yoelii, and the pro-inflammatory responses such as IL-1ß, TNF-α, and IL-6 after infection with P. yoelii are attenuated. These findings will be helpful for understanding the involvement of the pathogenic mechanism of malaria with the exported protein SRA.


Subject(s)
Antigens, CD , Antigens, Protozoan , Macrophages , Malaria , Plasmodium yoelii , Animals , Female , Humans , Mice , Antigens, CD/metabolism , Antigens, CD/immunology , Antigens, Differentiation, Myelomonocytic/metabolism , Antigens, Differentiation, Myelomonocytic/immunology , Antigens, Protozoan/immunology , Antigens, Protozoan/metabolism , Antigens, Surface/immunology , Antigens, Surface/metabolism , Cell Membrane/metabolism , Cell Membrane/immunology , Inflammation/immunology , Inflammation/metabolism , Macrophages/immunology , Macrophages/metabolism , Macrophages/parasitology , Malaria/immunology , Malaria/parasitology , NF-kappa B/metabolism , NF-kappa B/immunology , Plasmodium yoelii/immunology , Protein Binding , Signal Transduction
8.
bioRxiv ; 2024 Mar 09.
Article in English | MEDLINE | ID: mdl-38496594

ABSTRACT

Herein, we focus on native mass spectrometry (nMS) combined with a fast, tunable gas-phase charge reduction, electron capture charge reduction (ECCR), and illustrate its utility in the characterization of protein complex topology and glycoprotein heterogeneity. ECCR is illustrated to effectively spread the charge states of tetradecameric GroEL, illustrating Orbitrap m/z measurement out to greater than 100,000 m/z. For both the pentameric C-reactive protein and tetradecameric GroEL, our novel device combining ECCR with surface induced dissociation (SID) lowers the charge states and produces more topologically informative fragmentation. While more native-like fragmentation has previously been illustrated for complexes charge reduced by proton abstraction in solution, this is the first illustration that ECCR can lead to more native-like SID fragmentation of protein complexes. Application to protein glycosylation, one of the most common and diverse protein posttranslational modifications, is also illustrated because glycosylation is important for structural and functional properties and plays essential roles in many key biological processes. The immense heterogeneity resulting from variability in glycosylation sites and glycan composition and structure poses significant analytical challenges that hinder a mechanistic understanding of the biological role of glycosylation. Data for stabilized heavily glycosylated SARS-CoV-2 spike protein trimer and thyroglobulin dimer illustrate that ECCR enables significantly improved resolution of glycan heterogeneity. Without ECCR, the charge states of a glycoprotein complex are not resolved and average mass determination is available only through the use of charge detection mass spectrometry or mass photometry. With ECCR after narrow m/z selection, multiple glycoform m/z values are apparent, providing quick global, glycoform profiling and providing a future path for glycan localization on individual intact glycoforms (e.g., though top-down dissociation).

9.
Biomed Pharmacother ; 173: 116298, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38394850

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease; its cause is unknown, and it leads to notable health problems. Currently, only two drugs are recommended for IPF treatment. Although these drugs can mitigate lung function decline, neither can improve nor stabilize IPF or the symptoms perceived by patients. Therefore, the development of novel treatment options for pulmonary fibrosis is required. The present study investigated the effects of a novel compound, caffeic acid ethanolamide (CAEA), on human pulmonary fibroblasts and evaluated its potential to mitigate bleomycin-induced pulmonary fibrosis in mice. CAEA inhibited TGF-ß-induced α-SMA and collagen expression in human pulmonary fibroblasts, indicating that CAEA prevents fibroblasts from differentiating into myofibroblasts following TGF-ß exposure. In animal studies, CAEA treatment efficiently suppressed immune cell infiltration and the elevation of TNF-α and IL-6 in bronchoalveolar lavage fluid in mice with bleomycin-induced pulmonary fibrosis. Additionally, CAEA exerted antioxidant effects by recovering the enzymatic activities of oxidant scavengers. CAEA directly inhibited activation of TGF-ß receptors and protected against bleomycin-induced pulmonary fibrosis through inhibition of the TGF-ß/SMAD/CTGF signaling pathway. The protective effect of CAEA was comparable to that of pirfenidone, a clinically available drug. Our findings support the potential of CAEA as a viable method for preventing the progression of pulmonary fibrosis.


Subject(s)
Bleomycin , Caffeic Acids , Idiopathic Pulmonary Fibrosis , Humans , Mice , Animals , Bleomycin/toxicity , Antioxidants/metabolism , Lung , Idiopathic Pulmonary Fibrosis/chemically induced , Transforming Growth Factor beta/metabolism , Fibroblasts , Anti-Inflammatory Agents/adverse effects , Mice, Inbred C57BL
10.
Psychiatry Res ; 334: 115804, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38417224

ABSTRACT

Major depressive disorder (MDD) involves systemic changes in peripheral blood and gut microbiota, but the current understanding is incomplete. Herein, we conducted a multi-omics analysis of fecal and blood samples obtained from an observational cohort including MDD patients (n = 99) and healthy control (HC, n = 50). 16S rRNA sequencing of gut microbiota showed structural alterations in MDD, as characterized by increased Enterococcus. Metagenomics sequencing of gut microbiota showed substantial functional alterations including upregulation in the superpathway of the glyoxylate cycle and fatty acid degradation and downregulation in various metabolic pathways in MDD. Plasma metabolomics revealed decreased amino acids and bile acids, together with increased sphingolipids and cholesterol esters in MDD. Notably, metabolites involved in arginine and proline metabolism were decreased while sphingolipid metabolic pathway were increased. Mass cytometry analysis of blood immune cell subtypes showed rises in proinflammatory immune subsets and declines in anti-inflammatory immune subsets in MDD. Furthermore, our findings revealed disease severity-related factors of MDD. Interestingly, we classified MDD into two immune subtypes that were highly correlated with disease relapse. Moreover, we established discriminative signatures that differentiate MDD from HC. These findings contribute to a comprehensive understanding of the MDD pathogenesis and provide valuable resources for the discovery of biomarkers.


Subject(s)
Depressive Disorder, Major , Gastrointestinal Microbiome , Humans , Dysbiosis/complications , Multiomics , RNA, Ribosomal, 16S
11.
Nat Commun ; 15(1): 1843, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38418496

ABSTRACT

The development of facile tailoring approach to adjust the intrinsic activity and stability of atomically-precise metal nanoclusters catalysts is of great interest but remians challenging. Herein, the well-defined Au8 nanoclusters modified by single-atom sites are rationally synthesized via a co-eletropolymerization strategy, in which uniformly dispersed metal nanocluster and single-atom co-entrenched on the poly-carbazole matrix. Systematic characterization and theoretical modeling reveal that functionalizing single-atoms enable altering the electronic structures of Au8 clusters, which amplifies their electrocatalytic reduction of CO2 to CO activity by ~18.07 fold compared to isolated Au8 metal clusters. The rearrangements of the electronic structure not only strengthen the adsorption of the key intermediates *COOH, but also establish a favorable reaction pathway for the CO2 reduction reaction. Moreover, this strategy fixing nanoclusters and single-atoms on cross-linked polymer networks efficiently deduce the performance deactivation caused by agglomeration during the catalytic process. This work contribute to explore the intrinsic activity and stability improvement of metal clusters.

13.
Gene ; 895: 148028, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38007160

ABSTRACT

Spastic paraplegia 7 (SPG7) is an m-AAA protease subunit involved in mitochondrial morphology and physiology. However, its function in animal reproduction is yet to be evaluated. In this study, its molecular features, subcellular localization, and expression dynamics were investigated to analyze its potential function in the reproduction of male Phascolosoma esculenta, an economically important marine species in China. The full-length cDNA of P. esculenta spg7 (Pe-spg7) measures 3053 bp and encodes an 853-amino acid protein (Pe-SPG7). Pe-SPG7 includes two transmembrane domains, an AAA domain and a proteolytic domain. Amino acid sequence alignment revealed that SPG7 was conserved during evolution. The mRNA and protein expression of spg7 indicated its involvement in reproduction. Its expression was the highest in coelomic fluid, where spermatids develop, and it was significantly higher in the breeding stage than in the nonbreeding stage. SPG7 was mainly found in the mitochondria of spermatids in the coelomic fluid, indicating that it functions in this organelle in spermatids. Immunofluorescence experiments showed that SPG7 was expressed and colocalized in the mitochondria during spermiogenesis, suggesting its involvement in P. esculenta spermiogenesis. Therefore, SPG7 may participate in spermiogenesis by functioning in the mitochondria and regulate the reproduction of male P. esculenta. This study provided insights into the function of SPG7 in animal reproduction and P. esculenta gametogenesis.


Subject(s)
Mitochondria , Spastic Paraplegia, Hereditary , Animals , Male , ATPases Associated with Diverse Cellular Activities/genetics , ATPases Associated with Diverse Cellular Activities/metabolism , Mitochondria/genetics , Mitochondria/metabolism , Spermatogenesis/genetics , Spastic Paraplegia, Hereditary/genetics , Metalloendopeptidases/genetics
14.
Mol Med Rep ; 29(1)2024 01.
Article in English | MEDLINE | ID: mdl-37997800

ABSTRACT

Perinatal exposure of the neonatal lung to inflammation leads to decreased lung angiogenesis and the development of bronchopulmonary dysplasia (BPD). Notably, autologous cord blood mononuclear cells (ACBMNCs) can substantially prevent severe BPD and decrease the inflammatory response in surviving very preterm neonates. Angiopoietin­like protein 7 (Angptl7) is one of the main paracrine cytokines in cord blood stem cells, and is capable of stimulating human hematopoietic stem and progenitor cell expansion. The present study compared Angptl7 levels between the ACBMNCs infusion and control groups (cohort 1). Subsequently, the association between cord blood Angptl7 levels and BPD incidence in a cohort of very preterm neonates was assessed (cohort 2). The hypothesis was further verified in a lipopolysaccharide (LPS)­induced lung injury mouse model. The mRNA expression levels and protein concentrations of inflammatory cytokines in the lung tissue and mouse serum were measured using reverse transcription­quantitative PCR and ELISA, respectively. The number and diameter of lung vessels and macrophage infiltration were assessed using immunofluorescence staining. Compared with in the control group, Angptl7 levels were significantly higher in the ACBMNCs infusion group in cohort 1. In cohort 2, the cord blood Angptl7 levels were significantly lower in infants who later developed BPD. Multiple linear regression analysis showed that higher Angptl7 level was an independent protective factor for BPD. The concentrations of interleukin­6 and monocyte chemoattractant protein­1 were negatively correlated with cord blood Angptl7 level; whereas, vascular endothelial growth factor­A levels were positively correlated with Angptl7 levels. In the LPS­induced lung injury mouse model, the LPS group presented with a significant loss of pulmonary vessels and smaller vessel diameters, which were ameliorated in the Angptl7 treatment group. Furthermore, LPS­induced lung inflammation and macrophage infiltration were alleviated by Angptl7 treatment (P<0.05). In conclusion, the anti­inflammatory and proangiogenic effects of Angptl7 derived from cord blood stem cells may ameliorate BPD severity. The trial for cohort 1 was registered at ClinicalTrials.gov (trial registration no. NCT02999373; date registered, December 21, 2016).


Subject(s)
Bronchopulmonary Dysplasia , Lung Injury , Infant, Newborn , Infant , Pregnancy , Female , Humans , Animals , Mice , Bronchopulmonary Dysplasia/genetics , Vascular Endothelial Growth Factor A , Angiopoietin-Like Protein 7/genetics , Lung Injury/therapy , Lung Injury/complications , Fetal Blood , Lipopolysaccharides , Stem Cells , Cytokines , Anti-Inflammatory Agents
15.
Surg Endosc ; 38(3): 1398-1405, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38148402

ABSTRACT

BACKGROUND AND AIMS: With the continuous development of endoscopic technology, endoscopic resection (ER) has gradually become an optional method for the treatment of gastric gastrointestinal stromal tumors (GISTs). However, studies with a large sample or a long follow-up are lacking. Therefore, this research aims to evaluate the efficacy and safety of ER for gastric GISTs in the real-world setting with more than 300 enrolled patients and a follow-up period longer than 45 months. METHODS: From January 2013 to February 2023, 409 patients with a pathological diagnosis of GISTs after ER were retrospectively enrolled in this study. After excluding 86 patients with non-gastric GISTs, we assessed 323 patients with gastric GISTs. The main outcome measures were en bloc resection, complete resection, residual disease, recurrence, and complications. RESULTS: There were 194 (60.06%) females and 129 (39.94%) males, and the median age of the included patients was 58 years (51, 63). The median tumor size was 15.0 (10.0, 20.0) mm. According to the modified NIH criteria, 246 (75.85%) patients were classified as very low risk, 62 (19.20%) were classified as low risk, 12 (3.72%) were classified as moderate risk, and 3 (0.93%) were classified as high risk. A total of 287 (88.85%) patients achieved en bloc resection, and 287 (88.85%) also achieved complete resection. Only one patient showed residual and no recurrent lesions were noted during the follow-up. Regarding complications, three patients had complications, with a complication rate of 0.93%, and no severe complications requiring surgical intervention occurred. CONCLUSION: ER is an appropriate alternative method for the treatment of gastric GISTs, with an en bloc resection rate of 88.85% and a complication rate of 0.93%. No recurrence was noted during follow-up, even for GISTs with piecemeal resection.


Subject(s)
Gastrointestinal Stromal Tumors , Stomach Neoplasms , Male , Female , Humans , Middle Aged , Retrospective Studies , Gastroscopy/methods , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/pathology , Tertiary Care Centers , Treatment Outcome , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , China
16.
Shanghai Kou Qiang Yi Xue ; 32(4): 417-421, 2023 Aug.
Article in Chinese | MEDLINE | ID: mdl-38044738

ABSTRACT

PURPOSE: To investigate the value of PAR index combined with cephalometry in evaluating the efficacy of mild to moderate skeletal Class Ⅲ malocclusion. METHODS: Sixty-five adult patients with skeletal Class Ⅲ malocclusion were selected and divided into group C (camouflage therapy) and group S (orthodontic-orthognathic surgery)according to different treatment methods. PAR index and cephalometric values before and after treatment in each group were compared, and then the differences of PAR index and cephalometric values before and after treatment between the two groups were compared. The clinical effect was evaluated by these indexes. SPSS 25.0 software package was used for data analysis. RESULTS: In PAR index, the tooth alignment, occlusion, overjet, overbite, midline, total score and weighted total score after treatment of both groups were all significantly lower than those before treatment(P<0.001). The differences of left and right buccal bite and total posterior bite of group S before and after treatment was significantly larger than those of group C(P<0.001). In cephalometric measurement, the differences of SNA, NA-PA, L1-NB, U1-L1, U1-SN and L1-MP in group C before and after treatment were significantly different(P<0.05), while those in group S before and after treatment were SNA, SNB, ANB, NP-FH, NA-PA, L1-NB, U1-L1U1-SN and L1-MP(P<0.001). The differences of SNB, ANB and NP-FH before and after treatment in group S were significantly greater than those in group C(P<0.001). CONCLUSIONS: Both treatments are effective for adult patients with mild to moderate skeletal Class Ⅲ malocclusion. The effect of orthodontic-orthognathic treatment is better than camouflage therapy in occlusal relationship of posterior teeth, the position of mandible relative to cranium, the mutual position of upper jaw and lower jaw relative to cranium, and the degree of mandibular convexity. PAR index combined with cephalometric measurement can effectively judge the clinical effect of adult patients with mild to moderate skeletal Class Ⅲ malocclusion, which is a good evaluation method.


Subject(s)
Malocclusion, Angle Class III , Malocclusion, Angle Class II , Malocclusion , Orthognathic Surgery , Overbite , Humans , Adult , Cephalometry , Malocclusion, Angle Class III/surgery , Mandible , Maxilla , Malocclusion, Angle Class II/therapy , Malocclusion/therapy
17.
EMBO J ; 42(24): e114051, 2023 Dec 11.
Article in English | MEDLINE | ID: mdl-38059508

ABSTRACT

CDK11 is an emerging druggable target for cancer therapy due to its prevalent roles in phosphorylating critical transcription and splicing factors and in facilitating cell cycle progression in cancer cells. Like other cyclin-dependent kinases, CDK11 requires its cognate cyclin, cyclin L1 or cyclin L2, for activation. However, little is known about how CDK11 activities might be modulated by other regulators. In this study, we show that CDK11 forms a tight complex with cyclins L1/L2 and SAP30BP, the latter of which is a poorly characterized factor. Acute degradation of SAP30BP mirrors that of CDK11 in causing widespread and strong defects in pre-mRNA splicing. Furthermore, we demonstrate that SAP30BP facilitates CDK11 kinase activities in vitro and in vivo, through ensuring the stabilities and the assembly of cyclins L1/L2 with CDK11. Together, these findings uncover SAP30BP as a critical CDK11 activator that regulates global pre-mRNA splicing.


Subject(s)
RNA Precursors , RNA Splicing , RNA Precursors/genetics , RNA Precursors/metabolism , Phosphorylation , Cell Division , Cyclins/genetics , Cyclins/metabolism
19.
Sci Bull (Beijing) ; 68(22): 2817-2826, 2023 11 30.
Article in English | MEDLINE | ID: mdl-37919158

ABSTRACT

Early-onset Alzheimer's disease (EOAD) is a rare devastating subclassification of Alzheimer's disease (AD). EOAD affects individuals <65 years old, and accounts for 5%-10% of all AD cases. Previous studies on EOAD primarily focused on familial forms, whereas research on sporadic EOAD (sEOAD), which represents 85%-90% of EOAD cases, is limited. In this prospective cohort study, participants were recruited between 2018 and 2023 and included patients with sEOAD (n = 110), late-onset AD (LOAD, n = 89), young controls (YC, n = 50), and older controls (OC, n = 25). All AD patients fulfilled the diagnostic criteria based on biomarker evidence. Familial EOAD patients or non-AD dementia patients were excluded. Single molecule array technology was used to measure fluid biomarkers, including cerebrospinal fluid (CSF) and plasma amyloid beta (Aß) 40, Aß42, phosphorylated tau (P-tau) 181, total tau (T-tau), serum neurofilament light chain and glial fibrillary acidic protein (GFAP). Patients with sEOAD exhibited more severe executive function impairment and bilateral precuneus atrophy (P < 0.05, family-wise error corrected) than patients with LOAD. Patients with sEOAD showed elevated CSF and plasma P-tau181 levels (154.0 ± 81.2 pg/mL, P = 0.002; and 6.1 ± 2.3 pg/mL, P = 0.046). Moreover, precuneus atrophy was significantly correlated with serum GFAP levels in sEOAD (P < 0.001). Serum GFAP levels (area under the curve (AUC) = 96.0%, cutoff value = 154.3 pg/mL) displayed excellent diagnostic value in distinguishing sEOAD patients from the control group. These preliminary findings highlight the crucial role of tau protein phosphorylation in the pathogenesis and progression of sEOAD.


Subject(s)
Alzheimer Disease , Humans , Aged , Alzheimer Disease/diagnosis , tau Proteins/cerebrospinal fluid , Amyloid beta-Peptides/cerebrospinal fluid , Prospective Studies , Atrophy
20.
J Neuroimmunol ; 384: 578218, 2023 11 15.
Article in English | MEDLINE | ID: mdl-37801952

ABSTRACT

Levels of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) are useful biomarkers of disease activity and disability in neuromyelitis optica spectrum disorder (NMOSD). Here we investigated the association of sNfL and sGFAP levels with brain and spinal cord volumes in patients with NMOSD. Fifteen patients with NMOSD were enrolled in this prospective study. The median baseline level of sNfL was 42.2 (IQR, 16.1-72.6) pg/mL and decreased to 8.5 (IQR, 7.4-16.6) pg/mL at the end of the study. The reduction in sNfL was associated with a 7.5% loss of cervical spinal cord volume (CSCV) (p = 0.001). The levels of sGFAP reduced from 239.2 (IQR, 139.0-3393.3) pg/mL at baseline to 108.5 (IQR, 74.2-154.6) pg/mL. However, there was no strong correlation between sGFAP levels and CSCV changes during the follow-up period. Our data suggested that sNfL level is a useful biomarker for predicting spinal cord atrophy in patients with NMOSD.


Subject(s)
Neuromyelitis Optica , Humans , Intermediate Filaments , Prospective Studies , Spinal Cord/diagnostic imaging , Spinal Cord/pathology , Neurofilament Proteins , Biomarkers , Atrophy/pathology
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