AIM: To evaluate the diagnostic value of serum Th1-type cytokine levels and extraocular muscle-related parameters in thyroid-associated ophthalmopathy(TAO).METHODS: A retrospective study was conducted on 45 patients diagnosed with TAO in our hospital from January 2023 to December 2024, and 20 normal volunteers during the same period as controls. Venous blood samples of the patients were collected to detect the concentrations of Th1-type cytokines [interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), and interleukin-12(IL-12)] in the serum. Additionally, the end diastolic velocity(Ved), velocity maximum(Vmax), resistance index(RI)of the central retinal artery, as well as the thickness and left-right diameter of the medial rectus muscle were measured. Logistic regression model was used to analyze the risk factors of TAO, and receiver operating characteristic curve(ROC)was adopted to evaluate the diagnostic efficacy of each index for the occurrence of TAO.RESULTS: The general information of the two groups was comparable. Compared with the normal control group, the serum concentrations of IFN-γ and TNF-α in TAO patients were significantly increased, Ved and Vmax were lower than those in the control group, and RI and the thickness of the medial rectus muscle were higher than those in the control group(all P<0.05). Logistic regression analysis showed that serum IFN-γ concentration, Ved, Vmax, and the thickness of the medial rectus muscle were all risk factors for TAO. ROC curve analysis indicated that the AUCs of serum IFN-γ concentration, Ved, Vmax, and the thickness of the medial rectus muscle for the diagnostic efficacy of TAO were 0.756, 0.769, 0.732, and 0.642, respectively. The combined detection of IFN-γ, Ved, Vmax, and the thickness of the medial rectus muscle had an AUC of 0.840 and a Youden index of 0.59, which was superior to the detection of a single indicator.CONCLUSION: The levels of serum Th1-type cytokines and extraocular muscle-related ultrasound indicators have certain value in the diagnosis of TAO. The combination of IFN-γ, Ved, Vmax, and the thickness of the medial rectus muscle has better diagnosis efficiency in TAO, which can provide a certain reference for the early diagnosis of TAO.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

OBJECTIVES: To observe the evolution of intrahepatic macrophage polarization in mice with liver fibrosis induced by iron overload. METHODS: Thirty-two C57BL/6 mice (6-8 weeks) were randomized into control group (n=8) and liver fibrosis model group (n=24) induced by aidly intraperitoneal injection of iron dextran. At the 3rd, 5th, and 7th weeks of modeling, 8 mice in the model group were sacrificed for observing liver fibrosis using Masson, Sirius Red and immunohistochemical staining and detecting serum levels of ALT, AST and the levels of serum iron, ferritin, liver total Fe and ferrous Fe. iNOS⁺/F4/80⁺ cells and CD206⁺/F4/80⁺ cells were detected by double immunofluorescence assay to observe the proportion and distribution of M1 and M2 macrophages. The hepatic expressions of Arg-1, iNOS, IL-6, IL-10, and TNF‑α proteins were detected using Western blotting or ELISA, and the expression of CD206 mRNA was detected using RT-PCR. RESULTS: The mice in the model group showed gradual increase of fibrous tissue hyperplasia in the portal area over time, structural destruction of the hepatic lobules and formation of pseudolobules. With the passage of time during modeling, the rat models showed significantly increased hepatic expressions of α-SMA and COL-1, elevated serum levels of ALT, AST, Fe, ferritin, and increased liver total Fe and ferrous Fe levels. The expressions of M1 polarization markers IL-6, TNF‑α, and iNOS all increased with time and reached their peak levels at the 3rd week; The expressions of M2 polarization markers (IL-10 and Arg-1 proteins and CD206 mRNA) significantly increased in the 3rd week and but decreased in the 5th and 7th weeks. CONCLUSIONS Iron overload promotes M1 polarization of macrophages in mice. Liver fibrosis in the early stage promotes M2 polarization of macrophages but negatively regulate M2 polarization at later stages.
Animals ; Mice ; Mice, Inbred C57BL ; Iron Overload/pathology* ; Macrophages/metabolism* ; Male ; Liver Cirrhosis/etiology* ; Nitric Oxide Synthase Type II/metabolism* ; Interleukin-10/metabolism* ; Liver/pathology* ; Interleukin-6/metabolism* ; Mannose Receptor ; Tumor Necrosis Factor-alpha/metabolism* ; Mannose-Binding Lectins/metabolism* ; Arginase

The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

BACKGROUND:There is a significant correlation between sperm DNA fragmentation index and fertilization,embryonic development potential,embryo implantation,miscarriage,and offspring safety.However,its clinical reference value is affected by many factors,resulting in extremely limited clinical significance.This study took live birth as the outcome,corrected other confounding factors through propensity score matching,constructed the best clinical cutoff value of sperm DNA fragmentation index and live birth,and conducted internal and external tests on it,which has good predictive value and clinical application efficiency. OBJECTIVE:To investigate the reference threshold and offspring short-term security of in vitro fertilization-embryo transfer sperm DNA fragmentation index based on live birth. METHODS:A total of 1 921 patients who received in vitro fertilization and embryo transfer in Changzhou Maternal and Child Health Area Hospital from May 2019 to May 2021 were selected.On the basis of tendency matching tolerance of 0.02 and propensity score matching of 1:1,540 cases were successfully matched in each live birth group and non-live birth group,and the model group was established.135 patients who received in vitro fertilization and embryo transfer in Nanxishan Hospital of Guangxi Zhuang Autonomous Region were selected as the external validation group.The optimal clinical cutoff value of sperm DNA fragmentation index for live birth was investigated by the receiver operating characteristic curve.The accuracy and clinical application efficacy of the cutoff value were evaluated by restricted cubic spline curve,standard curve,clinical decision curve,clinical impact curve and internal and external validation tests. RESULTS AND CONCLUSION:(1)The DNA fragmentation index of sperm in the non-live birth group was significantly higher than that in the live birth group and had a significant negative correlation with live birth(r=-0.444,P<0.001).(2)Receiver operating characteristic curve results showed that the optimal cut-off value of DNA fragmentation index for live birth was 24.33%;the area under the curve was 0.775(0.746,0.804);the specificity was 72.60%;the sensitivity was 78.90%,and the accuracy was 75.70%.(3)Restricted cubic spline curve fitting the results of Logistic regression showed that when the sperm DNA fragmentation index was greater than 24.57%,the risk of clinical non-live birth increased.(4)The probability of Logistic regression analysis results showed that sperm DNA fragmentation index was a risk factor for live birth[OR(95%CI)=0.916(0.904,0.928),P<0.001],and when sperm DNA fragmentation index was greater than 27.78%,the probability of clinical live birth would be less than 50%.With the increase of sperm DNA fragmentation index by 1 unit,the probability of a live birth fell by 8.4%.(5)Internal and external to the validation of the clinical cutoff value showed that the cutoff point had certain clinical predictive value and accuracy.(6)Clinical decision curve and clinical impact curve results exhibited that the prediction model based on the clinical cut-off value had the maximum clinical net benefit value when the threshold probability was 0.22-0.73,and the ratio of loss to gain within the threshold probability range was always less than 1,which confirmed that the prediction model had good clinical application effectiveness.(7)The results of sperm DNA fragmentation index and offspring short-term security analysis showed that sperm DNA fragmentation index had no significant differences with preterm birth,body weight,deformity and sex.(8)These findings suggest that the optimal clinical cut-off value of sperm DNA fragmentation index for in vitro fertilization-embryo transfer live birth was 24.33%.The established clinical prediction model has good differentiation,accuracy and clinical application effectiveness.Sperm DNA fragmentation index has no significant impact on offspring short-term security,but large samples and long-term follow-up evaluation are still needed.

Objective To investigate the effect of local vibration therapy(LVT)on fine motor function of upper extremity and surface electromyography characteristics in children with spastic hemiplegic cerebral palsy(SHCP).Methods Sixty children with SHCP were divided into the observation group and the control group using random number table method,with 30 cases in each group.The control group was given conventional rehabilitation treatment(physical therapy,occupational therapy,sensory integration training,physiotherapy and rehabilitation therapy of traditional Chinese medicine),while the observation group received LVT for the affected upper extremity in addition to conventional rehabilitation treatment.Both groups were treated for 12 weeks.Fine motor function of upper extremity on the hemiplegic side[Peabody Developmental Motor Scale-Fine Motor(PDMS-FM),Fine Motor Function Measure(FMFM)]and root mean square(RMS)value of the biceps surface electromyography were compared between the two groups as well as before and after treatment.Results Compared with those before treatment,both groups showed increases in PDMS-FM scores for grasping energy range,visual-motor integration energy range,fine motor development quotient,FMFM scores for upper extremity joint mobility ability,grasping ability,operation ability,hand-eye coordination ability and total scores,but a decrease in RMS value of biceps brachii after treatment(P＜0.05).After treatment,PDMS-FM scores for grasping energy range and visual-motor integration energy range,FMFM scores for upper extremity joint mobility ability and grasping ability and total score were higher in the observation group than those in the control group.The RMS value of biceps brachii was lower in the observation group than that of the control group(P＜0.05).Conclusion LVT can enhance the effect of conventional rehabilitation on fine motor function of upper extremity and electromyography characteristics in children with SHCP.

Objective:To explore the effectiveness of the scaffolding teaching mode from the perspective of deep learning in basic nursing techniques course.Methods:From September 2023 to June 2024, 324 nursing students at Suzhou Vocational Health College in the 2023 cohort were selected as research subjects using convenience sampling. Three classes were designated as experimental group ( n=167), and three classes were designated as control group ( n=157). Control group received the traditional teaching mode, while experimental group received a scaffolding teaching mode from the perspective of deep learning on the basis of control group. Teaching effectiveness was evaluated using course grades, the Academic Self-Efficacy Scale, and the Measure Scale of Autonomous Learning Competencies of Nursing Undergraduates. Results:A total of 324 questionnaires were distributed and 324 valid questionnaires were collected, with a valid response rate of 100.00% (324/324). After teaching, the experimental group's nursing course grades were statistically higher than those of the control group ( P<0.05). After teaching, the experimental group's nursing students demonstrated statistically higher total scores and scores across all dimensions on the Academic Self-Efficacy Scale compared to the control group ( P<0.01). After teaching, the experimental group of nursing students scored statistically higher than the control group on the total score of the Measure Scale of Autonomous Learning Competencies of Nursing Undergraduates, as well as on the dimensions of self-management and learning cooperation ability ( P<0.01) . Conclusions:The implementation of the scaffolding teaching mode from the perspective of deep learning for basic nursing techniques course enhances vocational nursing students' academic performance, academic self-efficacy, and autonomous learning competencies.

Objective To evaluate the impact of setting a 4-day incubation time on the detection performance of bloodstream infection(BSI)pathogens by the BacTALERT VIRTUO blood culture system(VIRTUO).Methods Retrospectively collecting blood culture(BC)results from Zhongshan Hospital,Fudan University,from June 2021 to December 2023,and comparing the time-to-detection for clinically significant microorganisms.Results A total of 87 052 BC bottles were collected,of which 7 167(8.23%)were positive.95%of aerobic and anaerobic bottles were reported positive at 65.67 h and 91.2 h respectively.The average(median)time-to-detection for Staphylococcus aureus(S.aureus)was 21.76(16.08)h,Klebsiella pneumoniae(KP)was 15.32(11.65)h,Escherichia coli(E.coli)was 16.14(10.87)h,and Candida species was 35.2(28.5)h.Only 213 bottles(0.24%)were reported positive after 4 days of incubation;among them,88 bottles(41.31%)cultured Propionibacterium acnes(P.acnse).Medical chart reviews for BC reported positive after 96 h(4 days)showed no clinical significance.Simulated growth experiments were conducted on 11 fastidious bacteria,and the median detection time was only 10.8 h,indicating that an incubation time of 4 days is sufficient for fastidious bacteria.Conclusion A 4-day incubation is adequate for VIRTUO system.Reporting 1 day earlier to the doctors can reduce the positive rate of contaminants and the use of antimicrobial agents.

Objective The relationship between blood pressure variability(BPV)and short-term neurological prognosis in patients with aneurysmal subarachnoid hemorrhage(aSAH)was investigated.Methods The study conducted a retrospective analysis of clinical data from aSAH patients who underwent surgical treatment and were admitted to the ICU at Beijing Tiantan Hospital,Capital Medical University,from January 2023 to April 2024.BPV was quantitively assessed by calculating the standard deviation(SD),successive variation(SV),coefficient of variation(CV),and range of mean blood pressure(MBP).Patients were divided into two group based on discharge GOS scores:good prognosis[Glasgow Outcome Scale(GOS)4-5]and poor prognosis(GOS 1-3)groups.Comparative analyses were performed to evaluate differences in BPV metrics between the two groups,followed by multivariable logistic regression modeling to adjust for potential confounding factors and elucidate the association between BPV and clinical prognosis.Results A total of 150 patients were included,with 59 in the poor prognosis group and 91 in the good prognosis group.The poor prognosis group exhibited significantly elevated levels of MBP-SD[(9.85±3.20)mmHg vs.(8.04±2.31)mmHg,P<0.001],MBP-SV[(10.37±3.85)mmHg vs.(8.07±2.33)mmHg,P<0.001],MBP-CV(10.00±3.30%vs.8.19±2.33%,P<0.001),and MBP-range[(39.60±13.56)mmHg vs.(32.44±9.78)mmHg,P<0.05]compared to the good prognosis group.Cohen’s d values indicated moderate effect sizes for BPV differences(0.65,0.72,0.63,and 0.61,respectively).Multivariable logistic regression showed that MBP-SD(OR=1.22,95%CI:1.08-1.39,P=0.002)and MBP-SV(OR=1.19,95%CI:1.05-1.35,P=0.007)were independently associated with poor prognosis.Conclusion Elevated MBP-SD and MBP-SV within the first 24 hours postoperative period are independent predictors of unfavorable short-term neurological outcomes in aSAH patients.