Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.
Humans ; Male ; Infertility, Male/pathology* ; Acrosome/pathology* ; Sperm Tail/pathology* ; Pedigree ; Spermatozoa ; Adult ; Loss of Function Mutation ; Ciliary Motility Disorders/genetics* ; Spermatogenesis/genetics* ; Female

Objective To explore the effects of Rhodiola salidroside on regulating the mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK)/mammalian target of rapamycin(mTOR)signaling pathway and explore its impact on hippocampal neuron autophagy and apoptosis induced by oxygen-glucose deprivation/reperfusion(OGD/R).Methods The mouse hippocampal neuronal cell line HT22 was cultured in vitro and randomly divided into control group,OGD/R group,salidroside group,tert-butylhydroquinone(TBHQ)group,and salidroside+TBHQgroup.Except for control group,cell models were established by OGD/R induction in other groups.Cells in corresponding groups were treated with Rhodiola salidroside(500 μmol/L)and/or MAPK activator TBHQ(50 μmol/L)for 24 h.The lactate dehydrogenase(LDH)release rates were measured,cell apoptosis was detected by flow cytometry,and cell viability was assessed by MTT assay.Acridine orange(AO)staining was used to detect autophagy.Enzyme-linked immunosorbent assay(ELISA)was used to measure the expression levels of inflammatory cytokines including interleukins(IL)-6,IL-8,and IL-17,and tumor necrosis factor-α(TNF-α).Western blotting was performed to detect the expression levels of proteins related to apoptosis,autophagy,and the MAPK/ERK/mTOR signaling pathway.Results Salidroside(500 μmol/L)significantly enhanced the viability of OGD/R-induced HT22 cells(P＜0.05),without obvious effect on the viability of normally cultured HT22 cells(P＞0.05).Compared with control group,OGD/R group showed significantly increased LDH release rates,apoptosis rates,autophagosome formation rates,levels of IL-6,IL-8,IL-17 and TNF-α,expressions of Bcl-2-associated X protein(Bax),Cleaved Caspase-3,Caspase-3 and Beclin-1 protein,ratios of microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ,phosphorylation(p)-p38 MAPK/p38 MAPK,and p-ERK1/2/ERK1/2(P＜0.05),while cell viability and p-mTOR/mTOR ratio were significantly decreased(P＜0.05).Compared with OGD/R group,salidroside group had significantly reduced LDH release rates,apoptosis rates,autophagosome formation rates,levels of IL-6,IL-8,IL-17,and TNF-α,expressions of Bax,Cleaved Caspase-3,Caspase-3,Beclin-1 protein,and ratios of LC3-Ⅱ/LC3-Ⅰ ratio,p-p38 MAPK/p38 MAPK,and p-ERK1/2/ERK1/2(P＜0.05),while cell viability and p-mTOR/mTOR ratio were significantly increased(P＜0.05).The change of indicators in TBHQgroup showed an opposite trend to those in salidroside(P＜0.05).Compared with salidroside group,salidroside+TBHQgroup had significantly increased LDH release rates,apoptosis rates,autophagosome formation rates,levels of IL-6,IL-8,IL-17 and TNF-α,expressions of Bax,Cleaved Caspase-3,Caspase-3,Beclin-1 protein,and ratios of LC3-Ⅱ/LC3-Ⅰ,p-p38 MAPK/p38 MAPK,and p-ERK1/2/ERK1/2(P＜0.05),while cell viability and p-mTOR/mTOR ratio were significantly decreased(P＜0.05).Conclusion Salidroside may inhibit OGD/R-induced hippocampal neuron autophagy and apoptosis by blocking the activation and transmission of MAPK/ERK/mTOR signaling pathway.

Objective To investigate the protective effect of long non-coding RNA(lncRNA)small nucleolar RNA host gene 12(SNHG12)on neuronal damage induced by oxygen glucose deprivation/reoxygenation(OGD/R)by targeting microRNA(miR)-140-3p.Methods Human cortical neurons(HCN)were used to establish an OGD/R model,which was separated into OGD/R group,negative control(NC)group,SNHG12 group,SNHG12+miR-NC group,and SNHG12+miR-140-3p mimics group.Normal cultured HCN were also taken as the control(Ctrl)group.There were 6 repetitions in each group.Cell proliferation,apoptosis,lactate dehydrogenase(LDH)activity,mitochondrial membrane potential,lncRNA SNHG12 and miR-140-3p expression levels,and the interaction of lncRNA SNHG12 and miR-140-3p were detected.Results Compared with the control group,the survival rate of HCN,mitochondrial membrane potential,and lncRNA SNHG12 expression were lower in the OGD/R group,while the LDH activity,apoptosis rate,and miR-140-3p expression were higher(P＜0.05).Compared with the OGD/R group and NC group,the survival rate of HCN,mitochondrial membrane potential,and lncRNA SNHG12 expression were higher in the SNHG12 group,while the LDH activity,apoptosis rate,and miR-140-3p expression were lower(P＜0.05).Compared with the SNHG12+miR-NC group,the survival rate of HCN,mitochondrial membrane potential,and lncRNA SNHG12 expression were lower in the SNHG12+miR-140-3p mimics group,while the LDH activity,apoptosis rate,and miR-140-3p expression were higher(P＜0.05).Dual luciferase activity showed a targeted relationship between lncRNA SNHG12 and miR-140-3p(P＜0.05).Conclusion LncRNA SNHG12 may exert a protective effect against OGD/R-induced neuronal damage by inhibiting miR-140-3p.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To explore the effects of gypenosides(Gyp)on proliferation,apoptosis,and glycolysis of ovarian cancer cells,and exploring its impact on methyltransferase-like3(METTL3)mediated N6-methyladenosine(m6A)methylation in ovarian cancer and its mechanism of action.Methods The SKOV3 cells were divided into blank group(0.9％NaCl)and experimental-L,-M,-H groups(100,200 and 300 μg·mL-1 Gyp).The glucose consumption in cells were measured by kit.The expression levels of METTL3 mRNA were measured by quantitative real-time polymerase chain reaction(RT-qPCR).The apoptosis was determined by flow cytometry.Ovarian cancer model was constructed by subcutaneous injection of ovarian cancer SKOV 3 cell)in nude mice.After successful mold formation,10 mice were randomly divided into control group(0.9％NaCl)and experimental-L,-M,-H groups(50,100 and 150 mg·kg-1 Gyp),with 10 mice in each group.The RT-qPCR were used to detected the mRNA expression of glucose transporter 1(GLUT1)and hexokinase 2(HK2)in transplanted tumors.Results In SKOV3 cells,the glucose consumption of experimental-M,experimental-H and blank groups were(7.29±0.67),(6.15±0.22)and(15.69±0.70)μmol/1×105 cells;the relative expression levels of METTL3 mRNA were 0.47±0.01,0.30±0.01 and 1.02±0.01;the apoptosis rates were(13.52±0.50)％,(14.26±1.30)％and(3.50±0.78)％;the above indexes were statistically different between the experimental-M,-H groups and the blank group(all P＜0.01).In ovarian cancer transplantation tumor in nude mice,the relative expression levels of GLUT1 mRNA in experimental-M,experimental-H and blank groups were 0.52±0.03,0.29±0.01 and 1.02±0.02;the relative expression levels of HK2 mRNA were 0.54±0.04,0.32±0.01 and 1.01±0.02;the differences of above indexes were statistically significant between the experimental-M,-H groups and the blank group(all P＜0.01).Conclusion Gypenosides may exert anticancer effects in ovarian cancer by inhibiting glycolysis,which may be related to the inhibition of METTL3 mediated m6A methylation.

Objective To explore the effects of gypenosides(Gyp)on proliferation,apoptosis,and glycolysis of ovarian cancer cells,and exploring its impact on methyltransferase-like3(METTL3)mediated N6-methyladenosine(m6A)methylation in ovarian cancer and its mechanism of action.Methods The SKOV3 cells were divided into blank group(0.9％NaCl)and experimental-L,-M,-H groups(100,200 and 300 μg·mL-1 Gyp).The glucose consumption in cells were measured by kit.The expression levels of METTL3 mRNA were measured by quantitative real-time polymerase chain reaction(RT-qPCR).The apoptosis was determined by flow cytometry.Ovarian cancer model was constructed by subcutaneous injection of ovarian cancer SKOV 3 cell)in nude mice.After successful mold formation,10 mice were randomly divided into control group(0.9％NaCl)and experimental-L,-M,-H groups(50,100 and 150 mg·kg-1 Gyp),with 10 mice in each group.The RT-qPCR were used to detected the mRNA expression of glucose transporter 1(GLUT1)and hexokinase 2(HK2)in transplanted tumors.Results In SKOV3 cells,the glucose consumption of experimental-M,experimental-H and blank groups were(7.29±0.67),(6.15±0.22)and(15.69±0.70)μmol/1×105 cells;the relative expression levels of METTL3 mRNA were 0.47±0.01,0.30±0.01 and 1.02±0.01;the apoptosis rates were(13.52±0.50)％,(14.26±1.30)％and(3.50±0.78)％;the above indexes were statistically different between the experimental-M,-H groups and the blank group(all P＜0.01).In ovarian cancer transplantation tumor in nude mice,the relative expression levels of GLUT1 mRNA in experimental-M,experimental-H and blank groups were 0.52±0.03,0.29±0.01 and 1.02±0.02;the relative expression levels of HK2 mRNA were 0.54±0.04,0.32±0.01 and 1.01±0.02;the differences of above indexes were statistically significant between the experimental-M,-H groups and the blank group(all P＜0.01).Conclusion Gypenosides may exert anticancer effects in ovarian cancer by inhibiting glycolysis,which may be related to the inhibition of METTL3 mediated m6A methylation.

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.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

Objective: To investigate the association between gestational diabetes mellitus (GDM) and preterm birth subtypes. Methods: Based on the cohort of pregnant women in Anqing Prefectural Hospital, the pregnant women who received prenatal screening in the first or second trimesters were recruited into baseline cohorts; and followed up for them was conducted until delivery, and the information about their pregnancy status and outcomes were obtained through electronic medical record system and questionnaire surveys. The log-binomial regression model was used to explore the association between GDM and preterm birth [iatrogenic preterm birth, spontaneous preterm birth (preterm premature rupture of membranes and preterm labor)]. For multiple confounding factors, the propensity score correction model was used to compute the adjusted association. Results: Among the 2 031 pregnant women with a singleton delivery, the incidence of GDM and preterm birth were 10.0% (204 cases) and 4.4% (90 cases) respectively. The proportions of iatrogenic preterm birth and spontaneous preterm birth in the GDM group (n=204) were 1.5% and 5.9% respectively, while the proportions in non-GDM group (n=1 827) were 0.9% and 3.2% respectively, and the difference in the proportion of spontaneous preterm birth between the two groups was significant (P=0.048). Subtypes of spontaneous preterm were further analyzed, and the results showed that the proportions of preterm premature rupture of membranes and preterm labor in the GDM group were 4.9% and 1.0% respectively, while the proportions in the non-GDM group were 2.1% and 1.1% respectively. It showed that the risk of preterm premature rupture of membranes in GDM pregnant women was 2.34 times (aRR=2.34, 95%CI: 1.16-4.69) higher than that in non-GDM pregnant women. Conclusions: Our results showed that GDM might increase the risk of preterm premature rupture of membranes. No significant increase in the proportion of preterm labor in pregnant women with GDM was found.
Infant, Newborn ; Female ; Pregnancy ; Humans ; Premature Birth ; Diabetes, Gestational ; Obstetric Labor, Premature ; Hospitals ; Iatrogenic Disease