Objective: To investigate the distribution of pupil diameter and its association with myopia in school age children, providing ideas into the mechanisms of the role of pupil diameter in the onset and development of myopia. Methods: Adopting a combination of stratified cluster random sampling and convenience sampling method, 3 839 children from six schools in Shandong Province were included in September 2021. Pupil diameters distribution was analyzed by age, sex, and myopic status. Pearson correlation analysis was used to assess the relationship between pupil diameter and cycloplegic spherical equivalent (SE), as well as axial length (AL) and other variables. Propensity score matching (PSM) was applied to match myopic and non myopic children at a 1∶1 ratio based on age and sex. A generalized linear model (GLM) was constructed with pupil diameter as the dependent variable to identify independent factors influencing pupil size and its association with myopia. Results: The mean pupil diameter of school age children was (5.77±0.80)mm. Pupil diameter exhibited a significant increasing trend with age ( F =49.34， P trend ＜ 0.01). Myopic children had a significantly larger mean pupil diameter [(6.10±0.73)mm] compared to non myopic children [(5.62±0.79)mm] with a statistically significant difference( t=18.10, P <0.01). Multivariable GLM analysis, adjusted for age, amplitude of accommodation, and uncorrected visual acuity, revealed a negative correlation between pupil diameter and cycloplegic SE (before PSM: β =-0.089, after PSM: β =-0.063, both P ＜0.01). Conclusions Myopic school age children exhibite larger pupil diameters than their non myopic counterparts. Pupil diameter may serve as a potential indicator for monitoring myopia development in school age children.

Conventional cancer therapies, such as radiotherapy and chemotherapy, often damage normal cells and may induce new tumors. Oncolytic viruses (OVs) selectively target tumor cells while sparing normal cells. Most OVs used in clinical trials have been genetically engineered to enhance their ability to target tumor cells and activate immune responses. To develop a specific OV-based approach for treating cervical cancer, this study constructed an oncolytic adenovirus that delivered a base editor targeting oncogenes to achieve efficient killing of tumor cells through inhibiting tumor growth and directly lysing tumor cells. We utilized the human telomerase reverse transcriptase (TERT) promoter to drive the expression of adenovirus early region 1A (E1A) and successfully constructed the P-hTERT-E1A-GFP vector, which was validated for its activity in cervical cancer cells. Given the critical role of the MYC oncogene in the research of oncology, identifying efficient editing sites for the MYC oncogene is a key step in this study.Three MYC-targeting gRNAs were engineered and co-delivered with ABE8e base editor plasmids into HEK293T cells. Following puromycin selection, Sanger sequencing demonstrated differential editing efficiencies: MYC-1 (43%), MYC-2 (25%), and MYC-3 (35%), identifying MYC-1 as the most efficient editing locus. By constructing the P-ABEs-hTERT-E1A-GFP and P-MYC gRNA-hTERT-E1A-GFP vectors, we successfully packaged the virus and confirmed its specificity and efficacy. The experimental results demonstrate that this novel oncolytic adenovirus effectively inhibits the growth of HeLa cells in vitro, providing new experimental evidence and potential strategies for treating cervical cancer based on the HeLa cell model.
Humans ; Uterine Cervical Neoplasms/pathology* ; Oncolytic Viruses/genetics* ; Female ; HEK293 Cells ; Oncolytic Virotherapy/methods* ; Adenoviridae/genetics* ; Gene Editing/methods* ; Telomerase/genetics* ; Adenovirus E1A Proteins/genetics* ; Genetic Vectors/genetics* ; HeLa Cells

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

OBJECTIVES: To investigate the effect of orexin-A-mediated regulation of ionotropic glutamate receptors for promoting motor function recovery in rats with spinal cord injury (SCI). METHODS: Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (n=6), including a normal control group, a sham-operated group, and 4 SCI groups with daily intrathecal injection of saline, DNQX, orexin-A, or orexin-A+DNQX for 3 consecutive days after PCI. Motor function of the rats were evaluated using blood-brain barrier (BBB) score and inclined plane test 1 day before and at 1, 3, and 7 days after SCI. For patch-clamp experiment, spinal cord slices from newborn rats in the control, sham-operated, SCI, and SCI+orexin groups were prepared, and ventral horn neurons were acutely isolated to determine the reversal potential and dynamic indicators of glutamate receptor-mediated currents under glutamate perfusion. RESULTS: At 3 and 7 days after SCI, the orexin-A-treated rats showed significantly higher BBB scores and grip tilt angles than those with other interventions. Compared with those treated with DNQX alone, the rats receiving the combined treatment with orexin and DNQX had significantly higher BBB scores and grip tilt angles on day 7 after PCI. In the patch-clamp experiment, the ventral horn neurons from SCI rat models exhibited obviously higher reversal potential and greater rise slope of glutamate current with shorter decay time than those from sham-operated and orexin-treated rats. CONCLUSIONS Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.
Animals ; Spinal Cord Injuries/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Receptors, Ionotropic Glutamate/metabolism* ; Recovery of Function/drug effects* ; Orexins/pharmacology* ; Male ; Female ; Animals, Newborn ; Neuropeptides/pharmacology* ; Intracellular Signaling Peptides and Proteins/pharmacology*

Objective To investigate the characteristics of tremor in Parkinson disease （PD）， essential tremor （ET）， and neuronal intranuclear inclusion disease （NIID）. Methods The surface electromyography （sEMG） data of both upper limbs were collected from 73 patients with tremor （30 patients in PD group， 23 in ET group， and 20 in NIID group）， and the a power spectral analysis was used to investigate frequency characteristics. A one-way analysis of variance and the chi-square test were used for comparison of electrophysiological parameters on sEMG between the three groups. Results The ET group had a higher tremor frequency than the PD group （F=41.86， P<0.01）， while the PD group had a higher tremor frequency than the NIID group in resting state （F=41.86， P=0.002） and in postural state （F=41.86， P=0.011）. The PD group had a higher proportion of patients with alternating contractions than the NIID group in resting state （χ2=5.70， P=0.017） and in postural state （χ2=7.24， P=0.007）， as well as a higher proportion of such patients than the ET group （χ2=9.67， P=0.002）. The PD group also had a higher proportion of patients with harmonic resonances than the NIID group in resting state （χ2=4.64， P=0.031） and in postural state （χ2=7.73， P=0.005）， as well as a higher proportion of such patients than the ET group （χ2=6.52， P=0.011）. Conclusion The highest tremor frequency is observed in ET， while the lowest tremor frequency is observed in NIID； patients with PD have a higher proportion of individuals with alternating contractions or harmonic resonances than patients with NIID and ET.
Parkinson Disease ; Tremor

ObjectiveTo evaluate pharmacological effects of Shengmai injection（SMI）on cerebral ischemia and study its neuroprotective mechanism. MethodsMale specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a sham group， a model group， a low-dose SMI group（3 mL·kg^-1）， a middle-dose SMI group（6 mL·kg^-1）， a high-dose SMI group（12 mL·kg^-1）， and a Ginaton group（4 mL·kg^-1）according to the random number table method， with 12 rats in each group. The rat model of cerebral ischemia-reperfusion（MCAO/R）was prepared via the suture method. The administration groups were intraperitoneally injected with corresponding concentrations of SMI or Ginaton injection after reperfusion， which was conducted for 3 consecutive days. The sham group and model group were administered the equivalent volume of physiological saline. The pharmacological effects of SMI on brain injury in MCAO/R rats were evaluated by neurological function scores， cerebral infarction area， hematoxylin-eosin （HE） staining， Nissl staining， terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining， and Western blot. The dominant link and key protein of SMI treating cerebral injury were explored using proteomic analysis. The related mechanisms of SMI were further validated using enzyme-linked immunosorbent assay （ELISA）， Western blot， and chloride ion fluorescence probe with oxygen-glucose deprivation/reoxygenation（OGD/R）-treated PC12 cells and MCAO/R rats. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly decreased density of Nissl bodies and neurons（P<0.01）. Compared with the model group， the SMI groups exhibited significantly decreased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly increased density of Nissl bodies and neurons （P<0.05）. The proteomic analysis results showed that oxidative stress and inflammatory response were important processes of SMI intervening in MCAO/R injury， and the chloride intracellular channel protein 1 （CLIC1） was one of key proteins in its action network. The levels of representative indicators of oxidative stress and inflammatory response in the MCAO/R rats of the SMI groups were significantly reduced， compared with those in the model group（P<0.05， P<0.01）， and the expression levels of CLIC1 and downstream NOD-like receptor protein 3 （NLRP3） decreased （P<0.01）. In addition， the experimental results based on the OGD/R PC12 cells showed that SMI significantly increased the cell survival rate（P<0.01） and significantly decreased the intracellular chloride ion concentration（P<0.05）. ConclusionSMI has neuroprotective effects. Oxidative stress and inflammatory response are key processes of SMI intervening in MCAO/R injury. The potential mechanism is closely related to the regulation of CLIC1.

Objective:To evaluate the diagnostic value of native T1 mapping in differentiating Oxford classification (MEST-C) scores in patients with IgA nephropathy.Methods:In this prospective study, patients who underwent both T1 mapping and renal biopsy at the First Medical Center of the Chinese PLA General Hospital between April 2023 and October 2024 were consecutively enrolled. Two radiologists, blinded to clinical and pathological information, measured renal T1 mapping parameters, including cortical T1 (cT1), medullary T1 (mT1), the corticomedullary difference (ΔT1), and the corticomedullary ratio (T1 ratio). Clinical and renal biopsy data based on the Oxford classification from patients with IgA nephropathy were collected. The Oxford classification includes five indicators: Mesangial hypercellularity (M), Endocapillary hypercellularity (E), Segmental glomerulosclerosis or adhesion (S), Tubular atrophy/interstitial fibrosis (T), and Cellular or fibrocellular crescents (C). Spearman correlation analysis was applied to evaluate the associations between MEST-C scores and T1 parameters. The diagnostic performance of T1 parameters for discriminating among scores of the Oxford classification was analyzed using the receiver operating characteristic (ROC) curve.Results:A total of 124 patients with IgA nephropathy were included in this study [66 males, 58 females; age 19-70 years, 39 (30, 51) years]. Except for the E indicator, M, S, T, and C were significantly correlated with renal T1 values ( ρ=0.177-0.414, all P<0.05). cT1 showed the best diagnostic efficacy for the S score, with an area under the curve (AUC) of 0.798, a sensitivity of 68.7%, and a specificity of 88.0%. The best T1 parameter for differentiating the T score was the T1 ratio, with an AUC of 0.687, a sensitivity of 57.9%, and a specificity of 79.1%. Conclusion:Native T1 mapping can be used for the non-invasive assessment of the S and T scores in the Oxford classification of patients with IgA nephropathy.

Objective:To evaluate the effects of chlorinated organophosphate flame retardants (Cl-OPFRs) via respiratory and digestive tract exposure on multiple organs in mice.Methods:A short-term repeated exposure model of tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP) and tris(1, 3-dichloro-2-propyl) phosphate (TDCIPP) in mice was established through intratracheal instillation and oral gavage administration. The exposure doses were 0.7, 1 and 2 mg·kg -1·day -1, respectively, with continuous administration for 14 days. The organs of the heart, liver, spleen, lung, kidney, stomach, large intestine, small intestine, bladder and testis were collected and weighed to calculate the organ coefficients. The pathological and histological changes were observed by hematoxylin-eosin staining to quantitatively assess the effects of the three Cl-OPFRs on the various organs by using the pathology score. Results:Analysis of organ coefficients in tracheal drip-treated mice showed that the organ coefficients in the testes of the TCEP, TCIPP and TDCIPP groups were lower than those in the control group ( PTCEP-testis=0.045, PTCIPP-testis=0.012 and PTDCIPP-testis<0.001). The organ coefficients were lower in the lungs and small intestines of the TCEP group ( PTCEP-lung=0.006, PTCEP-small intestine=0.042). The organ coefficients for the stomach and large intestine were higher in the TDCIPP group ( PTDCIPP-stomach=0.014, PTDCIPP-large intestine=0.049). Analyses of gavage-contaminated mice showed that the organ coefficients for liver, stomach and small intestine in the TCEP and TDCIPP groups were higher than those in the control group ( PTCEP-liver=0.007, PTCEP-stomach=0.003, PTCEP-small intestine<0.001, PTDCIPP-liver=0.001, PTDCIPP-stomach=0.004, and PTDCIPP-small intestine<0.001). Histopathological analyses of the organs of tracheal drip dyed mice showed significant pathological damage in the lung tissue of the TCIPP group, mainly in the form of thickening of the interstitium, infiltration of inflammatory cells and alveolar collapse. The results of the analysis of gavage poisoned mice showed that TCIPP exposure could lead to blurring of the red and white medullary boundaries of spleen tissues, destruction of white medullary structures, etc., and induce small intestinal cryptitis. TDCIPP induced significant pathological damage to the liver tissues of mice, which mainly included cytoplasmic washout, infiltration of inflammatory cells, acute inflammation, and other injurious effects. Significant pathological damage to the intestinal tissues of mice was also observed. Conclusions:This study demonstrates that the toxic effects of Cl-OPFRs are significantly associated with exposure routes and compound specificity. Respiratory exposure predominantly induces TCIPP-mediated pulmonary injury, while digestive exposure causes TDCIPP-driven hepatointestinal toxicity. These findings provide preliminary evidence for the toxicity screening of Cl-OPFRs.

Objective Based on the best evidences to establish the practice plan of discharge preparation service for patients after receiving percutaneous transhepatic biliary drainage(PTBD),and to assess its clinical application value.Methods According to the PIPOST principle the clinical questions were proposed,the best evidences of discharge preparation service for patients after receiving PTBD were retrieved and summarized.The review indicators and review methods were formulated.The baseline review was carried out,the facilitators and barrier factors were analyzed,the change strategies were developed,the clinical transforms were implemented,and the patient outcomes were evaluated.Results After application of the evidences,the implementation of the review indicators of discharge preparation services after PTBD was improved.After discharge,the incidence of catheter complications(including catheter falling-off and puncture site skin infection)was decreased,and the difference was statistically significant(P＜0.05).There were no statistically significant differences in the incidences of tube obstruction and fluid extravasation.Conclusion The evidence-based practice of discharge preparation service for patients after receiving PTBD is helpful for improving the self-care ability of patients after discharge,reducing the incidence of tubular complications and improving the clinical outcome of patients.

Objective To investigate the expression of regional cerebral oxygen saturation(rSO2)in preterm infants with brain injury(BIPI)and its relationship with amplitude-integrated electroencephalogram(aEEG)parameters and neurodevelopment.Methods Retrospectively,116 cases of BIPI(Bilateral Intra-ventricular Perforation)born in the hospital between February 2022 and February 2023 were selected as the study subjects.According to the Expert Consensus on the Diagnosis and Prevention of Premature Infant Brain Injury,these cases were categorized into mild,moderate,and severe groups,with 59,35,and 22 cases,respectively.The study compared the general characteristics of premature infants with different brain injury levels.Regression analysis was conducted to identify the factors affecting brain injury in premature infants,and correlation analyses were performed on aEEG scores,rSO2,and GMS scores.ROC curve analysis was used to evaluate the value of combining brain oxygen saturation monitoring with aEEG in predicting abnormal whole-body motor quality assessment.Results On the 3rd and 7th days after birth,severe brain-injured premature infants had significantly lower rSO2 and aEEG scores compared to those with mild and moderate brain injuries(P<0.05).At 7 days,these infants also had lower scores for graph continuity,sleep-wake cycles,lower boundary amplitude,bandwidth,total score,rSO2,gestational age,and birth weight,and a higher proportion of abnormal developmental outcomes(PR+CS)(P<0.05).Multivariate logistic regression analysis revealed that the 3-day aEEG total score(OR=0.448,95％CI:0.094～0.890),7-day aEEG total score(OR=0.384,95％CI:0.058～0.726),3-day rSO2(OR=0.574,95％CI:0.398～0.750),and 7-day rSO2(OR=0.431,95％CI:0.115～0.777)were all protective factors for brain injury in premature infants,P<0.05.Correlation analysis showed that brain oxygen saturation was negatively correlated with aEEG scores and overall motor quality.The prediction value for abnormal overall motor quality using 7-day rSO2,aEEG,and the combination of 7-day rSO2 and 7-day aEEG scores was as follows:the positive predictive value for rSO2 was 86.46％,the negative predictive value was 96.85％,the sensitivity was 92.31％,the specificity was 92.21％,and the cut-off value was 0.845;The positive predictive value(PPV)of aEEG was 78.26％,the negative predictive value(NPV)was 96.86％,the sensitivity was 89.74％,and the specificity was 92.21％,with a cut-off value of 0.820.The positive predictive value(PPV)of 7-day rSO2 combined with 7-day aEEG score was 89.04％,the NPV was 96.88％,the sensitivity was 94.90％,and the specificity was 93.51％,with a cut-off value of 0.884,P<0.05.ROC curve analysis showed that the AUC of 7-day rSO2+7-day aEEG score was 0.895,De-long test P<0.005,indicating high predictive value for overall exercise quality.Conclusion Combined with rSO2 and EEG,the prediction of overall motor quality is better,which may have clinical value for excluding high-risk children.