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 effect of preoperative visits based on lean management theory in the preoperative psychological state of patients undergoing cardiopulmonary bypass surgery.Methods:According to the coin toss method,72 patients undergoing cardiopulmonary bypass surgery admitted to the Cardiothoracic Surgery Department of Chenzhou First People's Hospital from May 2024 to August 2024 were randomly divided into control group and observation group,with 36 cases in each group.The control group was given routine preoperative visits,and the observation group was given preoperative visits based on lean management theory on the basis of the control group.The psychological state,information demand level,vital signs and satisfaction of the patients were compared between the two groups 1 day before operation and when entering the room.Results:After intervention,the scores of State Anxiety Scale(S-AI)and Amsterdam Preoperative Anxiety and Information Scale(APAIS)were decreased in both groups,and the observation group were significantly lower than control group(P＜0.05).The vital signs(heart rate,systolic blood pressure and diastolic blood pressure)in observation group were lower than control group(P＜0.05).After intervention,the satisfaction of patients in observation group was significantly increased(P＜0.05).Conclusion:The implementation of preoperative visit based on lean management theory can help improve the preoperative psychological state of patients undergoing cardiopulmonary bypass surgery,eliminate anxiety,provide patients with more targeted surgical information support for patients,stabilize patients 'vital signs,and improve patients' satisfaction.

Objective To investigate the changes in the concentration of endothelial cell-specific molecule-1(ESM-1)in cerebrospinal fluid during the acute phase of patients with moderate to severe traumatic brain injury(TBI)and its relationship with injury severity and outcomes.Methods Eighty-four patients with moderate to severe TBI who underwent ventriculostomy for intracranial pressure(ICP)monitoring at Department of Neurosurgery,Jinshan Hospital,Fudan University from Jan 2020 to Dec 2023 were selected as the study subjects,and their clinical data were collected.Based on the Glasgow Coma Scale(GCS)upon admission,TBI patients were divided into moderate TBI group(GCS 9-12,n=48)and severe TBI group(GCS 3-8,n=36).According to the Glasgow Outcome Scale(GOS)at three months post-injury,the moderate to severe TBI patients were categorized into poor outcome group(GOS 1-3)and good outcome group(GOS 4-5).Patients were also classified based on ICP monitoring values into a normal ICP group(ICP≤15 mmHg),a mildly elevated ICP group(15 mmHg

Objective:To investigate the feasibility and advantages of 30°reverse trendelenburg combined with semi-prone position in single-port thoracoscopic surgery for lung cancer.Methods:This study is a prospective, randomized controlled trial. Between October 2022 and December 2023, patients with lung cancer who met the inclusion and exclusion criteria were prospectively enrolled at the Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University,and randomized using a simple randomization design to generate a random number table. Patients were allocated in a 1∶1 ratio to either the modified positioning group (30°reverse trendelenburg combined with semi-prone position) or the conventional positioning group (lateral decubitus position). Comparative analysis was performed on feasibility metrics including operative time, postoperative pain scores, surgeon and assistant fatigue levels, number of lymph nodes dissected, duration of postoperative chest tube drainage, and postoperative hospital stay. Inter-group comparisons were conducted using independent sample t-tests, χ2 tests or Kruskal-Wallis. Results:A total of 211 patients were included.The modified positioning group comprised 105 patients (58 males, 47 females) with an age of (56.2±10.3）years (range: 23 to 74 years). The conventional positioning group included 106 patients (55 males, 51 females) with an age of (57.8±11.7）years (range: 21 to 76 years). All patients underwent successful single-port thoracoscopic lung cancer surgery without severe perioperative complications. No statistically significant differences were observed between groups in operative time ((98±34) minutes vs. (114±36) minutes, t=-1.642, P=0.221), number of lymph nodes dissected (13.4±2.5 vs. 12.8±3.2, t=0.702, P=0.763), postoperative chest tube duration ((4.3±1.5) days vs. (5.1±1.8) days, t=-1.348, P=0.247), or postoperative hospital stay ((5.0±1.2) days vs. (5.6±1.5) days, t=-0.831, P=0.682). The modified positioning group demonstrated significantly lower postoperative day 1 pain scores on the visual analog scale (3.1±2.0 vs. 4.6±1.9, t=-4.321, P=0.027) and postoperative surgeon-reported fatigue scores (primary surgeon: 13.6±2.5 vs. 18.5±3.3, t=-6.963, P=0.002; assistant surgeon: 12.1±2.0 vs. 17.1±3.1, t=-6.133, P=0.003) compared with the conventional group, with all differences reaching statistical significance. Conclusions:The application of 30°reverse trendelenburg combined with semi-prone position during single-port thoracoscopic lung cancer surgery is both safe and feasible. Compared with the conventional lateral decubitus position, this modified positioning demonstrates significant advantages in reducing postoperative pain and alleviating surgical team fatigue (including both primary and assistant surgeons).

As a serine protease,thrombin can convert soluble fibrinogen into insoluble fibrin and plays a pivotal role in the coagulation cascade.Therefore,the accurate quantitative assay of thrombin levels is of great value in the evaluation of coagulation function,clinical screening and prognostic monitoring of coagulation-related diseases,and screening of drugs for targeted therapy.Existing methods for thrombin detection can be divided into two categories,e.g.,the assay of concentration levels using nucleic acid aptamers as the affinity elements and the assay of activity levels based on the hydrolytic cleavage of substrate peptides.In recent years,electrochemical biosensors have attracted much attention in thrombin detection due to high sensitivity,high selectivity,simple instrument,fast response,and good portability.In this review,the latest research progress in methods for electrochemical detection of thrombin was summarized,focusing on the detection principles and the applied signal amplification strategies of related electrochemical biosensors.In addition,the challenges with respect to the practical use of electrochemical thrombin biosensors and the prospects were discussed.

Cellular death in the body can occur through different processes,including apoptosis,pyroptosis and necrotic apoptosis,etc.PANoptosis is a newly discovered form of inflammatory cell death in recent years.It can be triggered by various stimulating factors and integrates multiple components that can induce cell death to assemble into various types of macromolecular complexes-PANoptosome,which then mediates cell death.Given the impact of PANoptosis on the entire disease spectrum,promoting or inhibiting its occurrence process may prevent the development of various diseases.The review summarizes the research progress on the occurrence mechanism of PANoptosis and its role in some diseases,and explores the crosstalk among multiple programmed cell death pathways,aiming to provide new ideas for the treatment of related diseases.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective:To synthesize a hydrolysis-resistant urushiol-modified monomer(UMM)to improve the hydrolysis resistance of light-cured composite resin,while reducing the volume shrinkage rate(VS),increasing the double bond conversion rate(DC),and mitigating the potential biosafety concerns of bisphenol A glycidyl methacrylate(Bis-GMA)monomer.Methods:UMM was synthesized by modifying urushiol via an acyl chloride reaction,and its structure was analyzed and characterized using Fourier transform infrared spectroscopy(FT-IR).Control group was consisted of Bis-GMA/triethylene glycol dimethacrylate(TEGDMA)without UMM,while 10%UMM,15%UMM,and 20%UMM groups were prepared by partially replacing Bis-GMA with UMM at mass fractions of 10%,15%,and 20%,respectively.The viscosity of UMM was measured using a rheometer.The DC of light-cured composite resin in various groups was detected by FT-IR spectroscopy,and the VS was calculated.The contact angle of light-cured composite resin in various groups was measured using the sessile drop method,and the water sorption and solubility values were calculated.The mechanical properties of light-cured composite resin in various groups were tested.The in vitro cytotoxicity of light-cured composite resin in various groups was evaluated using the cell counting kit-8(CCK-8)assay.Results:The FT-IR spectra results showed that the absorption peak of the hydroxyl group at 3 402 cm-1 disappeared,while characteristic absorption peaks of-C=O and-C=C appeared at 1 745 and 1 637 cm-1,indicating that urushiol successfully reacted with acryloyl chloride to form UMM.The viscosity of UMM ranged from 25.14 to 29.43 Pa·s.Compared with control group,the DC of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups was significantly increased(P<0.05),while the VS was significantly decreased(P<0.05),both in a dose-dependent manner.Compared with control group,the contact angle of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups was significantly increased(P<0.05).Compared with 10%UMM group,the contact angle of light-cured composite resin in 15%UMM and 20%UMM groups was further increased(P<0.05).Compared with control group,the water sorption and solubility values of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups were significantly decreased(P<0.05),showing a dose-dependent trend.After 24 h of water immersion,compared with control group,the flexural strength(FS)and elastic modulus(EM)of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups were significantly decreased(P<0.05),also in a dose-dependent manner.After 7 d of water immersion,compared with control group,the FS of light-cured composite resin in 10%UMM group was significantly increased(P<0.05),while that in 20%UMM group was significantly decreased(P<0.05).Compared with 10%UMM group,the FS of light-cured composite resin in 15%UMM and 20%UMM groups was significantly decreased(P<0.05),exhibiting a dose-dependent trend.Compared with control group,the EM of light-cured composite resin in 15%UMM and 20%UMM groups was significantly decreased(P<0.05),also in a dose-dependent manner.The relative growth rate(RGR)of the L929 cells in control,10%UMM,15%UMM,and 20%UMM groups was above 90%,with no statistically significant differences among groups(P>0.05),and all cytotoxicity results were qualified.Conclusion:A novel low-viscosity monomer UMM is successfully synthesized in this study.All UMM-containing light-cured composite resin formulations exhibit higher DC,lower VS,reduced water sorption and solubility values,improved hydrolysis resistance,and low cytotoxicity.UMM can serve as a potential resin monomer to enhance the hydrolysis resistance of light-cured composite resin.

Objective:Analysis of the composition of pathogen spectrum and prevalence characteristics in throat swabs of patients with acute respiratory infections (ARI) in Yucheng city, Henan province, from March to June 2023.Methods:After 1 153 throat swabs were collected from ARI patients in Yucheng, 18 respiratory pathogens were tested using a real-time fluorescence quantitative polymerase chain reaction (qPCR) method. The characterization of pathogens spectrum was analyzed.Results:A total of 1 153 throat swabs from ARI patients were collected from March to June 2023 in Yucheng, including 171 outpatients and 982 hospitalized patients. A total of 244 positive samples for common respiratory pathogens were detected (at least one pathogen per sample was detected). The total detection rate of respiratory pathogens was 21.16%, and the top three detection rates were, in descending order, human bocavirus (HBoV), enterovirus (EV), and human parainfluenza virus (HPIV). The main detection month for pathogens was May, with a detection rate of 42.3% (60/142). The main respiratory pathogens detected are HBoV, EV, and HPIV. The detection rate of the age group under 1 year old was the highest, at 25.1% (49/195), mainly consisting of HBoV, respiratory syncytial virus (RSV), and HPIV. The main clinical manifestations of respiratory pathogen-positive patients were fever and cough, and the clinical diagnosis was mainly lower respiratory tract infection, all of which were hospitalized patients.Conclusions:The respiratory pathogens in ARI patients were mainly HBoV, EV, and HPIV from March to June, 2023 in Yucheng. The peak of the epidemic was in May, mainly infecting children under 5 years of age.

Porcine hemagglutinating encephalomyelitis virus(PHEV)is one of the coronaviruses susceptible to swine populations.The non-structural protein 2(NS2)encoded by its genome is fre-quently deleted during the epidemic transmission of the virus,but its biological significance re-mains unclear.In order to explore the structure and function of the NS2 protein,this study utilized platforms such as ProtParam,TMHMM,NetPhos3.1,and ExPASy to analyze its physicochemical properties,spatial structure,genetic evolution,and post-translational modification characteristics.Meanwhile,the NS2 protein was expressed in eukaryotes and transcriptome sequencing was per-formed to clarify the biological processes it participates in.The results showed that the NS2 protein consists of 233 amino acids,with a molecular weight of 26.735 kDa,and a half-life of approximately 30 hours in mammals.It includes 13 phosphorylation sites,2 N-glycosylation sites,and 1 O-glyco-sylation site,with no signal peptide and strong hydrophilicity.The a-helix accounts for the highest proportion in NS2(43.78％),followed by random coils(36.05％).The homology of the NS2 pro-tein between the epidemic strains PHEV-CC14 and PHEV-JL/2008 in Northeast China is 99.57％.The NS2 protein is widely involved in the regulation of nerve-related functions,such as axon guid-ance and synaptic development.This study preliminarily clarified the biological function of the NS2 protein,providing a new perspective for understanding the pathogenic mechanism of PHEV.