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2.
Br Poult Sci ; : 1-7, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39250000

ABSTRACT

1. This study calculated descriptive statistics for the production traits of two broiler populations: 1) the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF white broilers), including fat and lean lines; and 2) the Guangxi yellow broilers. Their genetic parameters were estimated, including (co)variance components, heritability (h2) and genetic correlations (rg), using the REML method.2. Heritability estimates (h2) for NEAUHLF white broilers ranged from 0.07 to 0.61. Traits with high heritability (h2 >0.3) included body weight at 3, 5 and 7 weeks of age (BW3, BW5, BW7), carcass weight (CW), metatarsal circumference (MeC), liver weight (LW), gizzard weight (GW), spleen weight (SW) and testis weight (TeW), while in Guangxi yellow broilers, heritability estimates ranged from 0.18 to 0.76, with every trait exhibiting high heritability, except for SW (0.18).3. Positive genetic correlations for NEAUHLF were found (rg >0.3, ranging from 0.31 to 0.84) between BW7 and metatarsal length (MeL), MeC, body oblique length (BoL), chest angle (ChA), LW, GW, heart weight (HW) and SW. Genetic correlations between abdominal fat weight (AFW) and BW1, BW3, BW5, CW, MeL, keel length (KeL), BoL and LW were positive (rg >0.3, ranging from 0.31 to 0.58).4. Among the Guangxi population, BW (125 d of age) showed strong positive genetic correlations with all other traits (rg >0.3, ranging from 0.30 to 0.99), while AFW displayed strong positive genetic correlations with leg muscle weight (LeW), CW, BW and thigh diameter (TD) (rg >0.3, ranging from 0.44 to 0.51).5. It was concluded that the characteristics of the two populations were different, which means there is a need to use different strategies when performing the breeding work to improve productivity and efficiency in both broiler populations.

3.
Neurologia (Engl Ed) ; 39(7): 540-548, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39232591

ABSTRACT

BACKGROUND: Hemifacial spasm (HFS) is a debilitating disease characterized by involuntary tonic and clonic contractions of muscles innervated by the facial nerve. Botulinum toxin A (BTX-A) is the first-line option and the most effective medical treatment for HFS. The objective of this study was to evaluate the effect of BTX-A therapy on the physical and mental health of HFS patients. METHODS: Participants included 65 HFS patients and 65 matched healthy controls in the study. Cornell Medical Index (CMI) self-assessment questionnaire was used to detect the psychological health of all participants. Local injection of BTX-A was applied, and the Cohen hierarchical criteria were employed to stratify the degree of spasticity, further evaluating the efficacy of BTX-A before and two months after treatment in HFS patients. The HFS patients at two months post-treatment were re-evaluated by CMI self-assessment questionnaire, and the evaluated factors of these patients were compared with those of patients before treatment. RESULTS: The scores of somatization, depression, anxiety, inadaptation, sensitivity, anger, tension, M-R, and total scores in the HFS group were significantly higher than those in the control group (all P<0.05). Two months post-treatment, among 65 HFS patients who received with BTX-A treatment, 42 (64.6%) were completely relieved, 16 (24.6%) were significantly relieved, 7 (10.8%) were partially relieved, and 0 (0%) cases were invalid, and the total effective rate was 89.2%. Two months after BTX-A treatment, the scores of somatization, tension, anxiety, depression, sensitivity, M-R and total scores of patients with HFS were lower than those before treatment (all P<0.05). CONCLUSIONS: Patients with HFS are often accompanied by somatization, anger, inadaptation, sensitivity, anxiety, depression, and tension. BTX-A can not only alleviate the symptoms of HFS, but also improve the somatization, tension, anxiety, depression, and sensitivity.


Subject(s)
Botulinum Toxins, Type A , Hemifacial Spasm , Neuromuscular Agents , Humans , Hemifacial Spasm/drug therapy , Botulinum Toxins, Type A/therapeutic use , Female , Male , Middle Aged , Neuromuscular Agents/therapeutic use , Adult , Mental Health , Treatment Outcome , Aged , Surveys and Questionnaires , Anxiety/drug therapy , Depression/drug therapy
4.
J Dent Res ; : 220345241271078, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39290151

ABSTRACT

N6,2'-O-dimethyladenosine (m6Am), a common mRNA modification in eukaryotic capped mRNAs, plays a pivotal role in cellular functions and disease progression. However, its involvement in host inflammation remains elusive. Here, we demonstrate that loss of m6Am methyltransferase phosphorylated CTD interacting factor 1 (PCIF1) attenuates periodontal inflammation in whole-body and myeloid lineage-specific knockout mouse models. Pcif1 deletion inhibits macrophage phagocytosis and migration through m6Am-Csf1r signaling. In addition, colony-stimulating factor-1 receptor (CSF1R) is identified as a potential target for the treatment of periodontitis. We thus reveal a previously unrecognized role for PCIF1-mediated m6Am modification in governing macrophage responses and periodontal inflammation.

5.
Zhonghua Fu Chan Ke Za Zhi ; 59(8): 591-599, 2024 Aug 25.
Article in Chinese | MEDLINE | ID: mdl-39187406

ABSTRACT

Objective: To analysis the risk factors for major adverse cardiovascular event (MACE) in pregnant women with valvular heart disease (VHD) and to construct a risk prediction model. Methods: The clinical data of 245 pregnant women with VHD who were hospitalized in Beijing Anzhen Hospital from January 1, 2012, to June 1, 2023 were retrospectively analyzed, including general information, pre-pregnancy and pregnancy-associated cardiac conditions, and MACE. Univariate analysis and logistic regression models were employed to identify risk factors for MACE during pregnancy among pregnant women with VHD. Furthermore, a predictive model was constructed and internal validation was conducted using bootstrap techniques. Results: (1) Among 245 pregnant women with VHD, the incidence of MACE was 18.0% (44/245), and the most common MACE was heart failure (61.4%, 27/44). The mitral valve was the most frequently affected valve (64.9%, 159/245). Prior to pregnancy, the most common type of valve surgery undertaken was mechanical valve replacement, representing 31.4% (77/245) of surgeries. In contrast, among those pregnant women who did not undergo valve surgery before pregnancy, the most common lesion type was mitral regurgitation (17.6%, 43/245). (2) Comparing the maternal and infant outcomes of warfarin, low molecular weight heparin (LMWH) and LMWH sequential with warfarin, the fetal loss rate (36%, 15/42) and malformation rate (7%, 3/42) were the highest, but the MACE rate (12%, 5/42) was the lowest in warfarin group. The fetal loss rate (1/19), malformation rate (1/19) and artificial valve thrombosis rate (0) of LMWH sequential with warfarin were the lowest, and the fetal loss rate and artificial valve thrombosis rate of the three anticoagulation methods were statistically significant (all P<0.05). (3) There were no significant differences in gestational age, age of diagnosis of heart disease, weight at delivery, pre-pregnancy body mass index, proportion of multiparous women and chronic medical history between women with MACE and those without MACE (all P>0.05). (4) Binary logistic regression analysis identified the following as risk factors for MACE during the second trimester of pregnancy among pregnant women with VHD: pre-pregnancy cardiac symptoms, history of corrective surgery for congenital heart disease, pregnancy risk grade Ⅴ, anticoagulation with LMWH during pregnancy, and arrhythmia (all P<0.05). Based on the results of multivariate analysis, a receiver operating characteristic curve was constructed, with an area under the curve of 0.837, indicating good discriminative ability. The calibration plot demonstrated a close alignment between the standard curve and the calibration prediction curve, suggesting excellent calibration of the model. Conclusions: Pregnant women with VHD are at a high risk of experiencing MACE during gestation. Five risk factors, including pre-pregnancy cardiac symptoms, history of corrective surgery for congenital heart disease, pregnancy risk grade Ⅴ, anticoagulation with LMWH, and arrhythmia, could aid in identifying high-risk pregnant women.


Subject(s)
Heart Valve Diseases , Pregnancy Complications, Cardiovascular , Humans , Female , Pregnancy , Risk Factors , Heart Valve Diseases/surgery , Heart Valve Diseases/complications , Heart Valve Diseases/epidemiology , Retrospective Studies , Pregnancy Complications, Cardiovascular/epidemiology , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Adult , Incidence , Heart Failure/epidemiology , Heart Failure/etiology
6.
ESMO Open ; 9(8): 103651, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39059062

ABSTRACT

BACKGROUND: APG-1387 is a novel second mitochondrial-derived activator of caspases mimetic, small-molecule inhibitor targeting inhibitor of apoptosis proteins. We report results from two phase I trials evaluating the tolerability, safety, and antitumor activity of APG-1387 monotherapy and APG-1387 plus toripalimab [a programmed cell death 1 (PD-1) inhibitor] for advanced solid tumors. PATIENTS AND METHODS: Participants aged ≥18 years who had histologically confirmed advanced solid tumors with no appropriate standard of care (or refractory to standard care) were eligible. Patients received escalating intravenous doses of APG-1387 alone or combined with fixed-dose toripalimab (240 mg every 3 weeks) in a '3 + 3' design. Primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) in the monotherapy trial, and recommended phase II dose (RP2D) in the combination therapy trial. Secondary endpoints included the pharmacokinetic and pharmacodynamic profiles and preliminary efficacy in both trials. RESULTS: In the monotherapy trial, 28 subjects were enrolled and received ≥1 treatment cycle. No DLT was reported among the 28 subjects, and the MTD was not reached. One participant (3.6%) had a grade ≥3 treatment-related adverse event (TRAE) of alanine aminotransferase elevation. In efficacy analysis of 23 participants, none achieved an objective response, and the disease control rate was 21.7%. In the combination trial, 22 subjects were enrolled and included in all analyses. There was one DLT of grade 3 lipase elevation. The MTD was not reached. Four grade ≥3 TRAEs occurred in three participants (13.6%), with the most common being lipase elevation (n = 2). The RP2D was 45 mg weekly. The objective response rate was 13.6%, with complete response achieved in one subject, and the disease control rate was 54.5%. CONCLUSIONS: APG-1387 45 mg weekly plus toripalimab was well tolerated and is recommended for further study, with preliminary clinical activity observed in study participants with advanced solid tumors.


Subject(s)
Antibodies, Monoclonal, Humanized , Neoplasms , Humans , Neoplasms/drug therapy , Middle Aged , Male , Female , Aged , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Inhibitor of Apoptosis Proteins/metabolism , Maximum Tolerated Dose , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Pentanoic Acids
7.
Zhonghua Gan Zang Bing Za Zhi ; 32(6): 508-516, 2024 Jun 20.
Article in Chinese | MEDLINE | ID: mdl-38964893

ABSTRACT

Objective: To explore the related factors of thrombocytopenia (TCP) occurrence in patients with cirrhosis. Methods: A cross-sectional study was conducted. Inpatients with an initial diagnosis of cirrhosis at Peking University First Hospital from January 1, 2010 to December 31, 2020 were included. Clinical data such as demographic characteristics, etiology of cirrhosis, complications of cirrhosis, laboratory indicators, Child-Pugh grade, invasive procedures, and mortality during hospitalization were collected. A logistic regression model was used to explore the related factors of TCP occurrence in patients with cirrhosis. Categorical variables were compared by the χ(2) test. The inter-group comparison was performed using continuous variables, a t-test, one-way analysis of variance (ANOVA), or a nonparametric test. Results: There were a total of 2 592 cases of cirrhosis. 75 cases with incomplete clinical data were excluded. 2 517 cases were included for analysis. The median age was 58 (50, 67) years. Males accounted for 64%. 1 435 cases (57.0%) developed TCP, and 434 cases (17.2%) had grade 3-4 TCP. Gender, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and concomitant esophagogastric varices (EGV) were the major factors associated with TCP. Females were more prone to combine with TCP (OR=1.32, 95%CI: 1.12-1.56, P=0.001). Patients combined with EGV (OR=3.09, 95%CI: 2.63-3.65, P<0.001) were more prone to develop TCP, which was associated with the increased incidence of hypersplenism (P<0.001). Patients with PBC (OR=0.64, 95%CI: 0.50-0.82, P<0.001) and PSC (OR=0.23, 95%CI: 0.06-0.65, P=0.010) were less prone to develop TCP, which was due to the shorter prothrombin time and better coagulation function of PBC patients (P<0.001), and the lower proportion of hypersplenism in combined PSC patients (P=0.004). Patients with TCP and grade 3-4 TCP had a higher rate of hemostatic procedures (P<0.05), but a lower rate of liver biopsy (P<0.05). Patients with grade 3-4 TCP had a higher nosocomial mortality rate compared to those without (P=0.004). Conclusion: TCP is common in patients with cirrhosis. However, TCP occurrence is higher in female patients with EGV and lower in patients combined with PBC and PSC. TCP affects invasive procedures and is associated with adverse outcomes.


Subject(s)
Liver Cirrhosis , Thrombocytopenia , Humans , Cross-Sectional Studies , Thrombocytopenia/etiology , Male , Middle Aged , Female , Liver Cirrhosis/complications , Aged , Risk Factors , Logistic Models , Liver Cirrhosis, Biliary/complications , Adult
8.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39082890

ABSTRACT

Ambient pressure may influence the thermal path between the absorber and heat sink of resistive bolometers and thus impact the calibration parameters. This effect is investigated for metal resistive bolometer sensors as used in bolometer diagnostics on fusion experiments. Measurements in the test facility IBOVAC indicate that pressure has no effect up to 10-3 mbar. However, a significant change in the cooling time constant is observed for pressures above 10-2 mbar, a reduction up to a factor of three at 1 mbar. The measurements performed in N2 and He atmospheres and simulations in H2 indicate no difference between the results from different gas species up to 10-3 mbar and less than 10 % up to 0.1 mbar. A model based on the thermal conductivity of the surrounding gas combined with the geometry of the sensor holder successfully demonstrates that the additional cooling path through the gas, which may vary between the measurement and reference absorbers, can explain the measurement results. Applying the model to the geometry of a sensor holder designed for port-mounted bolometer cameras in ITER led to design modifications that should help reduce the impact of high environmental pressures on the bolometer measurements. Similarly, it can be assumed that applying the model to the geometries and sensors of operating bolometer diagnostics can help correct the measurements and improve the understanding of plasma radiation in the case of high pressures at the location of bolometer sensors.

10.
Br Poult Sci ; : 1-9, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39036858

ABSTRACT

1. The proliferation of granulosa cells is vital for the development and recruitment of hen ovarian prehierarchical follicles (PF). The RAB23 protein is a member of the Rab family, belonging to the GTPase family. This study studied the regulatory roles of the RAB23 gene in PF.2. The expression of RAB23 was significantly increased in granulosa cells (GC) during PF growth and was highest in GC at 6-8 mm diameter (p < 0.05). The RAB23 protein was mainly expressed in the GC, oocytes (OC) as well as somatic cells (SC) of the PF.3. The mRNA expression of FSHR, CCND1,CYP11A1, StAR and HSD3B1 was significantly increased in the siRNA RAB23 group (p < 0.05). Additionally, protein expression of FSHR, CCND1, CYP11A1, HSD3B1 was significantly increased (p < 0.05) after GC were transfected with RAB23-specific siRNA. Protein expression of StAR in the siRNA RAB23 group was numerically higher than that in the positive control (PC) and negative control (NC) groups. The GC proliferation rate and progesterone synthesis of the prehierarchical follicles in hen ovaries were markedly increased in vitro (p < 0.05).4.This study revealed that RAB23 might play an inhibitory role in GC proliferation and progesterone synthesis during the prehierarchical follicles development in vitro.

11.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 36(2): 219-220, 2024 May 08.
Article in Chinese | MEDLINE | ID: mdl-38857970

ABSTRACT

Plasmodium falciparum malaria, caused by Plasmodium falciparum infection, is an Anopheles mosquito-transmitted infectious diseases, which predominantly occurs in tropical areas of Africa. P. falciparum malaria is characterized by complex and atypical clinical manifestations, and high likelihood of misdiagnosis and missing diagnosis, and may be life-threatening if treated untimely. This case report presents the diagnosis and treatment of a P. falciparum malaria case with acute abdominal pain as the first symptom.


Subject(s)
Abdominal Pain , Malaria, Falciparum , Humans , Malaria, Falciparum/diagnosis , Malaria, Falciparum/complications , Abdominal Pain/etiology , Abdominal Pain/parasitology , Male , Plasmodium falciparum/isolation & purification , Plasmodium falciparum/physiology , Adult
12.
Zhonghua Yi Xue Za Zhi ; 104(22): 2074-2078, 2024 Jun 11.
Article in Chinese | MEDLINE | ID: mdl-38858218

ABSTRACT

This study reports a family of patients with 11ß-hydroxylase deficiency (11ß-OHD) caused by a novel mutation in the CYP11B1 gene, and analyzes its clinical and genetic characteristics. The clinical data of a patient with intractable hypertension at Air Force Medical Center on May 16, 2014 were retrospectively analyzed. The patient was clinically diagnosed with congenital adrenal cortical hyperplasia. The clinical data of the patient were further collected and the peripheral blood samples of the patient, his parents and his sister were collected for CYP11B1(NM_000497) gene sequencing, suggesting that the patient had compound heterozygous mutations in exon 1:c.199delG, p.Glu67Lysfs*9 and exon 5:c.905_907 delATGinsTT, p.Asp302Valfs*23, both of which were pathogenic variants. The patient's father and sister carried heterozygous mutations in exon 1:c.199delG, p.Glu67Lysfs*9, and the mother carried heterozygous mutations in exon 5:c.905_907delATGinsTT, p.Asp302Valfs*23. This study is the first to report a new compound heterozygous mutation in exon 1:c.199delG and exon 5 c.905_907 delATGinsTT of CYP11B1 gene, enriching the database of 11ß-OHD mutations and providing information to further understand the genetic mechanism of the disease.


Subject(s)
Adrenal Hyperplasia, Congenital , Mutation , Steroid 11-beta-Hydroxylase , Humans , Steroid 11-beta-Hydroxylase/genetics , Adrenal Hyperplasia, Congenital/genetics , Male , Female , Retrospective Studies , Exons , Heterozygote , Pedigree
13.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 36(2): 174-178, 2024 Apr 29.
Article in Chinese | MEDLINE | ID: mdl-38857962

ABSTRACT

OBJECTIVE: To investigate the bacterial community diversity in human Demodex mites, so as to provide insights into unraveling the role of human Demodex mites in them caused infectious diseases. METHODS: From June to July 2023, Demodex mites were collected from the faces of college students in a university in Wuhu City using the adhesive tape method, and the V4 region of 16S ribosomal RNA (16S rRNA) gene and the internal transcribed spacer (ITS) gene of nuclear ribosomal DNA were amplified on an Illumina PE250 high-throughput sequencing platform. Sequencing data were spliced according to the overlapping relations and filtered to yield effective sequences, and operational taxonomic units (OTUs) was clustered. The diversity index of obtained OUTs was analyzed, and the structure of the bacterial community was analyzed at various taxonomic levels. RESULTS: A total of 57 483 valid sequences were obtained using 16S rRNA gene sequencing, and 159 OUTs were classified according to similarity. Then, OUTs at a 97% similarity were included for taxonomic analyses, and the bacteria in Demodex mites belonged to 14 phyla, 20 classes, 51 orders, 72 families, and 94 genera. Proteobacteria was the dominant phylum, and Vibrio, Bradyrhizobium and Variovorax were dominant genera. A total of 56 362 valid sequences were obtained using ITS gene sequencing, and 147 OTUs were obtained, which belonged to 5 phyla, 17 classes, 34 orders, 68 families, and 93 genera and were annotated to Ascomycota, Basidiomycota and Chytridiomycota, with Ascomycota as the dominant phylum, and Alternaria alternata, Epicoccum, Penicillium, and Sarocladium as dominant genera. CONCLUSIONS: There is a high diversity in the composition of bacterial communities in human Demodex mites, with multiple types of microorganisms and high species abundance.


Subject(s)
Bacteria , Mites , RNA, Ribosomal, 16S , Humans , Animals , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification , Mites/microbiology , Mites/genetics , Mites/physiology , RNA, Ribosomal, 16S/analysis , RNA, Ribosomal, 16S/genetics , Biodiversity , Phylogeny
14.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 36(2): 201-206, 2024 Mar 29.
Article in Chinese | MEDLINE | ID: mdl-38857967

ABSTRACT

Tuberculosis (TB) remains one of the biggest infectious killers worldwide. Vaccine is the most satisfactory tool for prevention of TB; however, Bacillus Calmette-Guérin (BCG), the widely used vaccine in clinical for the prevention of TB, has limitations in protective effects. Development of novel TB vaccines is therefore of urgent need. Currently, there are 15 novel TB vaccine candidates in clinical trials, including live-attenuated vaccines, inactivated vaccines, subunit vaccines and viral-vectored vaccines, which open the door for the ultimate target of the End TB Strategy. This review summarizes the latest advances in the development of TB vaccines in global clinical trials, so as to provide insights into TB control.


Subject(s)
Clinical Trials as Topic , Tuberculosis Vaccines , Tuberculosis , Humans , Tuberculosis Vaccines/immunology , Tuberculosis/prevention & control , Vaccine Development
15.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(5): 859-866, 2024 May 20.
Article in Chinese | MEDLINE | ID: mdl-38862443

ABSTRACT

OBJECTIVE: To explore differentially expressed endoplasmic reticulum stress-associated genes (ERSAGs) in aortic dissection (AD) and their correlations with immune cell infiltration to identify new therapeutic targets for AD. METHODS: Two AD mRNA expression datasets (GSE190635 and GSE98770) were downloaded from GEO database for analysis of differentially expressed genes between the aorta of AD patients and normal aorta using R software. ERSAGs dataset was downloaded from GeneCards website, and GeneMANIA database was used to analyze the protein-protein interaction network of the differentially expressed ERSAGs and the proteins interacting with these genes. Based on GSE98770 dataset we analyzed the distributions of 22 immune cells within the aortic wall of AD patients using CIBERSORT package of R software. Surgical aortic wall specimens were obtained from 10 AD patients and 10 non-AD patients for detecting AGER mRNA expression using qRTPCR, and the upstream transcriptional factors, miRNAs, and chemicals targeting AGER were analyzed using the TRRUST database and NetworkAnalyst database. RESULTS: Bioinformatic analysis suggested significant differential expression of AGER in AD, which interacted with 20 proteins involved in pattern recognition receptor signaling pathway, positive regulation of DNA-binding transcription factor activity, myeloid leukocyte migration, leukocyte migration, and regulation of the I-κB kinase/NF-κB signaling. In AD, AGER expression level was positively correlated with Treg cell abundance (r=0.59, P < 0.05). The results of qRT-PCR demonstrated significantly lower expression of AGER mRNA in AD than in non-AD patients (1.00±0.30 vs 1.76±0.68, P < 0.05). ROC curve analysis showed that at the cut-off value of 1.335, AGER had an AUC of 0.86 (95% CI: 0.67-1.00, P= 0.0073) for predicting AD. Three transcriptional factors, 3 miRNAs, and 27 chemicals were predicted in the AGER regulatory network. CONCLUSION: AGER is lowly expressed in the aorta of AD patients and may influence the occurrence of AD through Treg cells.


Subject(s)
Aortic Dissection , Endoplasmic Reticulum Stress , Humans , Aortic Dissection/genetics , Aortic Dissection/metabolism , Endoplasmic Reticulum Stress/genetics , Protein Interaction Maps/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Computational Biology , Signal Transduction , Gene Expression Profiling , Gene Regulatory Networks , Aorta/metabolism
16.
J Dent Res ; 103(7): 734-744, 2024 07.
Article in English | MEDLINE | ID: mdl-38752256

ABSTRACT

N6-methyladenosine (m6A) modification, a eukaryotic messenger RNA modification catalyzed by methyltransferase-like 3 (METTL3), plays a pivotal role in stem cell fate determination. Calvarial bone development and maintenance are orchestrated by the cranial sutures. Cathepsin K (CTSK)-positive calvarial stem cells (CSCs) contribute to mice calvarial ossification. However, the role of m6A modification in regulating Ctsk+ lineage cells during calvarial development remains elusive. Here, we showed that METTL3 was colocalized with cranial nonosteoclastic Ctsk+ lineage cells, which were also associated with GLI1 expression. During neonatal development, depletion of Mettl3 in the Ctsk+ lineage cells delayed suture formation and decreased mineralization. During adulthood maintenance, loss of Mettl3 in the Ctsk+ lineage cells impaired calvarial bone formation, which was featured by the increased bone porosity, enhanced bone marrow cavity, and decreased number of osteocytes with the less-developed cellular outline. The analysis of methylated RNA immunoprecipitation sequencing and RNA sequencing data indicated that loss of METTL3 reduced Hedgehog (Hh) signaling pathway. Restoration of Hh signaling pathway by crossing Sufufl/+ alleles or by local administration of SAG21 partially rescued the abnormity. Our data indicate that METTL3 modulates Ctsk+ lineage cells supporting calvarial bone formation by regulating the Hh signaling pathway, providing new insights for clinical treatment of skull vault osseous diseases.


Subject(s)
Cathepsin K , Hedgehog Proteins , Methyltransferases , Osteogenesis , Signal Transduction , Skull , Animals , Methyltransferases/metabolism , Methyltransferases/genetics , Osteogenesis/physiology , Osteogenesis/genetics , Mice , Hedgehog Proteins/metabolism , Cell Lineage , Cranial Sutures , Stem Cells , Zinc Finger Protein GLI1/metabolism , Zinc Finger Protein GLI1/genetics
17.
Physiol Res ; 73(2): 205-216, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38710050

ABSTRACT

ADHD is a common chronic neurodevelopmental disorder and is characterized by persistent inattention, hyperactivity, impulsivity and are often accompanied by learning and memory impairment. Great evidence has shown that learning and memory impairment of ADHD plays an important role in its executive function deficits, which seriously affects the development of academic, cognitive and daily social skills and will cause a serious burden on families and society. With the increasing attention paid to learning and memory impairment in ADHD, relevant research is gradually increasing. In this article, we will present the current research results of learning and memory impairment in ADHD from the following aspects. Firstly, the animal models of ADHD, which display the core symptoms of ADHD as well as with learning and memory impairment. Secondly, the molecular mechanism of has explored, including some neurotransmitters, receptors, RNAs, etc. Thirdly, the susceptibility gene of ADHD related to the learning and impairment in order to have a more comprehensive understanding of the pathogenesis. Key words: Learning and memory, ADHD, Review.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Memory Disorders , Attention Deficit Disorder with Hyperactivity/psychology , Attention Deficit Disorder with Hyperactivity/genetics , Humans , Animals , Memory Disorders/psychology , Memory Disorders/etiology , Learning , Disease Models, Animal , Learning Disabilities/psychology , Learning Disabilities/etiology , Memory
18.
Eur Rev Med Pharmacol Sci ; 28(6): 2207-2216, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38567584

ABSTRACT

OBJECTIVE: We investigated the associations between osteoporosis (OP) and systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) in postmenopausal women. PATIENTS AND METHODS: This retrospective study included 966 postmenopausal women. Logistic regression and receiver operating characteristic curve (ROC) analyses were applied to explore the relationships between SII, NLR, MLR, and PLR with the bone mineral density (BMD) and risk of OP. RESULTS: Logistic regression analyses showed that SII, PLR, NLR, and MLR had independent negative associations with the OP risk. The ROC curve analysis showed that SII, NLR, and MLR predicted a low BMD, with NLR having the highest predictive value (area under the curve = 0.624). SII > 504.09, PLR > 131.87, NLR > 2.02, and MLR > 0.12 correlated with a particularly high OP risk. CONCLUSIONS: High levels of SII, PLR, NLR, and MLR were associated with a high OP risk. In particular, NLR > 2.02 strongly predicted the risk of OP, thereby representing a valuable and convenient inflammatory marker of the OP risk.


Subject(s)
Lymphocytes , Postmenopause , Humans , Female , Retrospective Studies , Blood Cell Count , Neutrophils , Inflammation
19.
Eur Rev Med Pharmacol Sci ; 28(6): 2288-2296, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38567591

ABSTRACT

OBJECTIVE: Based on data from the National Health and Nutrition Examination Survey (NHANES), this study aimed to investigate the effect of high levels of systemic immune inflammation (SII) on hepatic steatosis by conducting a population-based cross-sectional survey of research subjects. SUBJECTS AND METHODS: The population included 5,119 participants from the NHANES 2017-2020 cycle who were selected as the research subjects. We used (neutrophil count × platelet count)/lymphocyte count as the formula for calculating SII. The formula for calculating HSI levels was 8 × the ratio of [alanine aminotransferase (ALT) / aspartate aminotransferase (AST)] + body mass index (BMI) + 2 (with diabetes mellitus) + 2 (for women). HSI=36 was taken as the cut-off value for evaluating hepatic steatosis. Multivariate logistic regression analysis was used to evaluate the relationship between hepatic steatosis and SII in different models. Subgroup analysis was used to explore the relationship between different subgroups of SII and hepatic steatosis. Interaction analyses were used to assess the heterogeneity. RESULTS: Out of a total of 5,119 participants, hepatic steatosis was observed in 2,742 individuals. Multivariate logistic regression showed that the independent risk factor for hepatic steatosis was a high SII level (OR=1.33, 95% CI: 1.11-1.49, p<0.05). After adjusting for differences in BMI and HSI using propensity score matching (PSM), bariatric surgery also reduced SII risk. CONCLUSIONS: There is a correlation between SII and hepatic steatosis, and bariatric surgery can effectively reduce SII risk in the hepatic steatosis population.


Subject(s)
Fatty Liver , Inflammation , Humans , Female , Cross-Sectional Studies , Nutrition Surveys , Risk Factors
20.
Zhonghua Zhong Liu Za Zhi ; 46(4): 354-364, 2024 Apr 23.
Article in Chinese | MEDLINE | ID: mdl-38644271

ABSTRACT

Objective: To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China. Methods: Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (<60, 60-<70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values. Results: A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening. Conclusion: To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.


Subject(s)
Early Detection of Cancer , Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/blood , Prostate-Specific Antigen/blood , Aged , Middle Aged , Early Detection of Cancer/methods , Age Factors , ROC Curve , China , Sensitivity and Specificity , Mass Screening/methods , Area Under Curve
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