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.

Background The respiratory toxicity of inhaled polyhexamethylene guanidine (PHMG) has been extensively studied since the humidifier disinfectant incident. However, the impacts of inhalation of PHMG on the immune system are not comprehensively studied yet. Objective To explore the effects of inhalation of PHMG disinfectant aerosol on major immune organs and immune cells in mice. Methods Thirty male C57BL/6J mice (6-8 weeks old) were randomly divided into three groups: control, low-dose (0.1 mg·m⁻³ PHMG), and high-dose (1.0 mg·m⁻³ PHMG), with ten mice in each group. The mice were administered by oral-nasal inhalation of PHMG aerosol for 4 h per day, 5 d per week for 4 weeks consecutively. After designed treatment, venous blood was collected from the inner canthus of the eyes of mice and peripheral hematological indicators were measured with a blood analyzer. Then the mice were sacrificed by cervical dislocation and the lung, thymus, spleen, and femur were isolated. Lung, thymus, and spleen were weighed and organ coefficients were calculated, and single cell suspensions of thymus, spleen, and bone marrow were prepared to analyze lymphocytes phenotypes and proportions by flow cytometry. Results The body weight of mice in the high-dose group was lower than that of mice in the control group (P<0.01) from the 7th day of inhalation, and decreased by 15.74% compared with that of mice in the control group at the end of inhalation (P<0.01). The lung coefficients of both the low-dose and high-dose groups were higher than that of the control group (P<0.01), the thymus coefficient of mice in the high-dose group was lower than that of the control group (P<0.05), but the spleen coefficient did not change significantly (P>0.05). Leukocyte count [(1.49±0.22)×10⁹·L⁻¹], lymphocyte count [(0.96±0.36)×10⁹·L⁻¹] and its proportion [(63.13±14.96)%] in the peripheral blood of mice in the high-dose group were lower than those in the control group [(2.69±0.25)×10⁹·L⁻¹, (2.33±0.28)×10⁹·L⁻¹, and (86.23±3.40)%, respectively] (P<0.01), whereas red blood cell count [(12.32±0.46)×10¹²·L⁻¹], hemoglobin count [(175.25±4.65) g·L⁻¹], and hematocrit [(53.55±0.70)%] in the peripheral blood of mice in the high-dose group were higher than those in the control group [(11.11±0.37)×10¹²·L⁻¹, (160.67±4.04) g·L⁻¹, and (45.10±9.75)%, respectively] (P<0.05). Compared with the control group, the proportion of CD4+ CD8+ double-positive T cells decreased (P<0.05), the proportions of CD4+ T cells and CD8+ T cells increased (P<0.05), and the amounts of CD8+, CD4+ CD8+, CD4+, and CD4- CD8- cells decreased (P<0.05) in the thymus of mice of the high-dose group, the proportion of CD4+ T cells in the spleen of the high-dose group increased (P<0.05), the proportions and amounts of T cells, CD4+ T cells, and CD8+ T cells in the bone marrow of the high-dose group increased (P<0.05). Conclusion Inhalation of PHMG may cause thymic atrophy, disrupt T-lymphocyte development, and lead to an imbalance in the number of immune cells in the bone marrow, peripheral blood, and spleen, suggesting that inhalation of PHMG induces immune dysfunction.

Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg⁻¹ ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg⁻¹; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg⁻¹) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg⁻¹ and 21.90 mg·kg⁻¹, and those of male mice were calculated to be 58.62 mg·kg⁻¹ and 54.31 mg·kg⁻¹, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg⁻¹ and 11.99 mg·kg⁻¹ for female mice, and 16.28 mg·kg⁻¹ and 10.47 mg·kg⁻¹ for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg⁻¹ and 19.92 mg·kg⁻¹ for female mice, and 24.74 mg·kg⁻¹ and 14.08 mg·kg⁻¹ for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg⁻¹, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.

Objective To explore the adverse drug event signal of piperacillin-tazobactam(TZP)and promote rational and safe use of drugs in clinic.Methods The proportional unbalance method was used to mine the signals of all TZP adverse events(ADE)reports from the inception of FDA adverse event reporting system(FAERS)to March 2024.The basic situation of the the reported cases and the relevant information of adverse reactions were analyzed.Results A total of 20 620 513 ADE reports were obtained for the main suspected drugs,and 6 489 ADE reports were reported for TZP as the main suspected drug.543 ADE signals were mined,involving 25 system organ classifications(SOC).43 ADE signals were detected by secondary screening,and 17 ADE signals were new ADR signals.The top 5 ADE signals involved in SOC classification were skin and subcutaneous tissue disorders,general disorders and administration site reactions,various examinations,infections and infectious disease,and blood and lymphatic system disorders.The top 5 preferred terms for ADE signal number were rash,pyrexia,acute kidney injury,pruritus and thrombocytopenia.Penicillins had several ADE signals on blood and lymphatic system diseases.TZP led to thrombocytopenia with the largest number of cases,and oxacillin led to agranulocytosis with the highest proportional reporting ratio.The median treatment course of TZP induced leukopenia was 11.00 days,and the median accumulated dose was 148.50 g.The median treatment course of TZP induced agranulocytosis was 14.00 days,and the median accumulated dose was 216.00 g.The median treatment course of TZP induced thrombocytopenia was 7.00 days,and the median accumulated dose was 87.00 g.Conclusion The adverse reactions related to skin and subcutaneous tissue diseases should be paid close attention to during medication,which may be more common than those of gastrointestinal diseases.When large doses or long courses of TZP are clinically used,close attention should be paid to the adverse reactions related to blood and lymphatic system disorders to avoid serious ADE.

The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective: To analyze the epidemiological and etiological characteristics of hand-foot-mouth disease (HFMD) in Tongren City during 2018 to 2022, so as to provide the reference for HFMD effective prevention and control. Methods: Monitoring data on HFMD in Tongren City from 2018 to 2022 was collected from National Infectious Disease Reporting Information Management System. Descriptive epidemiological method was conducted on the data analysis. Results: A total of 14 376 cases of HFMD were reported in Tongren City during 2018 to 2022, the average annual incidence rate of HFMD was 89.43/100 000. Totally 47 severe cases were reported, accounting for 0.33% of the total cases. The incidence rates of HFMD were generally declining trend during 2018 to 2022 (124.68/100 000, 95.37/100 000, 78.50/100 000, 61.63/100 000, 87.80/100 000) ( χ 2 trend =393.05, P <0.01), mainly occurred during April to July (48.13%), among children under 5 years old (95.72%). During 2018 to 2022, a total of 967 laboratory diagnosed cases reported in different years, regions, age groups showed significant differences in pathogen composition ratio ( χ 2=169.62, 456.65 , 167.96, P <0.05). From 2018 to 2022, the dominant pathogen of HFMD was constantly changing. Other enteroviruses were the dominant epidemic strains in 2018 and 2022 (33.04%, 37.62%), CoxA 6 was the dominant epidemic strain in 2019 to 2020 ( 68.75 %, 50.78%), and CoxA16 was the dominant epidemic strain in 2021(43.30%).In 2018, one case was infected with CoxA16 and EV71.The difference of pathogen composition ratio varied in different years ( χ 2=169.62, P <0.01). Conclusions The prevalence of HFMD in Tongren City has showed a declining trend during 2018 to 2022, and the dominant strain of HFMD has changed in recent years. The pathogen monitoring of HFMD should be strengthened to timely grasp the distribution and changes of pathogens, so as to provide a basis for the precise prevention and control of HFMD.

Objective:To explore the feasibility of synthetic diamond detector in use for Flash radiation dosimetry by designing a diamond dosimeter and conducting a series of dosimetric characteristic tests.Methods:A diamond detector system prototype with real-time current output was developed using a CIVIDEC? B1HV diamond sensor and designing a large dynamic range current measurement circuit based on the pre-integration method. The dose (dose-rate) response linearity was tested under irradiation from both electron beam and X ray ultra-high dose rate. Dose (dose-rate) calibration was performed against a medical accelerator to gain the charge-dose transfer coefficient.Results:Good linear correlation ( R2 = 0.99) between detector output charge and reference dose per pulse was shown under electron beam irradiation of 0.08-0.50 Gy/pulse. Good linearity ( R2 = 0.99) is also shown under irradiation from electron beam with ultra-high dose rate (400 Gy/s) and conventional dose rate (0.5 Gy/s). Strictly linear correlation ( R2 = 1) was shown between detector output integrated charge and reference dose under X ray irradiation at ultra-high average dose rate (75.5 Gy/s) and conventional average dose rate (0.5 Gy/s). The charge-dose and current-dose rate conversion factors for practical use were 0.751 7 μC/Gy and 0.753 5 μA·Gy·s -1, respectively. Conclusions:Considerable linearity of the diamond detector dose responses were shown under irradiation both from electron beam and X-ray beam, which could provide a relatively rapid and accurate dosimetry for Flash preclinical experiments. Furthermore, diamond detectors have great potential in the quality assurance for Flash radiotherapy.

Objective:To examine the burden of caregivers for elderly Parkinson's patients(PD)and to analyze the mediating effects of social support on primary PD caregivers' burden and their quality of life.Methods:In this cross-sectional study, 281 primary caregivers for elderly Parkinson's patients who visited the Department of Neurology's outpatient clinics of Qilu Hospital of Shandong University from January to May 2021 were surveyed via a convenience sampling method, with 242 valid questionnaires(86.1%). The Chinese versions of the Caregiver Burden Questionnaire, Social Support Rating Scale and 36-Item Short Form Health Survey were used for the investigation.Pearson correlation analysis was used to establish a structural equation model for the influence of social support in the burden and quality of life of caregivers for PD patients.The mediating effects were tested using Process v2.16.3 and re-tested using AMOS.The mediating effects were validated with Bootstrap.Results:Primary caregivers' scores on burden, social support and quality of life were(26.9±23.1), (40.5±8.7)and(593.7±163.3), respectively.Caregiver burden was negatively correlated with social support(r=-0.482, P<0.01), and social support was positively correlated with quality of life(r=0.513, P<0.01). Caregiver burden was negatively correlated with quality of life( r=-0.654, P<0.01), The validated mediating effects showed caregiver burden's direct effects on quality of life(95% CI: -0.38-0.61)and mediating effects of social support(95% CI: -0.08-0.21), not including 0, indicating that the care burden of primary caregivers for elderly PD patients was not only able to predict their quality of life, but also predict their quality of life through the mediating effects of social support(direct effect: -0.50 and mediating effect: -0.14, accounting for 78.0% and 22.0%, respectively, of the total effect of -0.64). Conclusions:Care burden and social support are important factors affecting the quality of life of primary caregivers for elderly PD patients.Reducing care burden can not only directly affect the quality of life, but also indirectly affect the quality of life by increasing social support.

Objective:To evaluate the effects of intrathecal morphine and fentanyl on interferon (IFN)-γ levels in hippocampus and plasma of rats with incisional pain.Methods:Ninety-six healthy male Sprague-Dawley rats in which intrathecal catheters were successfully inserted, weighing 180-220 g, aged 6-8 weeks, were divided into 4 groups ( n=24 each) using a random number table method: normal saline group (group NS), incisional pain group (group P), morphine and fentanyl group (group MF) and morphine and fentanyl with incisional pain group (group MFP). Incisional pain model was established in group P and group MFP.At 20 min before the model was established, a 50 μl mixture of morphine 5 μg/kg and fentanyl 0.25 μg/kg was intrathecally injected in group MF and group MFP, while normal saline 50 μl was injected intrathecally in group NS and group P. At 24 h before establishment of the model (T 0) and at 1, 6, 24, 48 and 72 h after establishment of the model (T 1-5), 6 mice were randomly selected from each group for determination of the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL). The animals were sacrificed and hippocampal tissues and blood samples from the inferior vena cava were collected for determination of IFN-γ levels in hippocampal tissues and plasma (by enzyme-linked immunosorbent assay). Results:Compared with group NS, MWT was significantly decreased and TWL was shortened at T 1-5, and IFN-γ concentration in plasma was decreased at T 2, 3 and T 5 in group P, MWT was increased and TWL was prolonged at T 1-3 in group MF, MWT was decreased and TWL was shortened at T 1-3 in group MFP, and IFN-γ concentration in plasma was decreased at T 2 in MF and MFP groups ( P<0.05). Compared with group P, MWT was increased, TWL was prolonged at T 1-5, and IFN-γ concentration in plasma was increased at T 2, 3 and T 5 in MF and MFP groups ( P<0.05). Compared with group MF, MWT was decreased and TWL was shortened at T 1-4, and IFN-γ concentration in plasma was increased at T 2 and T 3 in MFP ( P<0.05). There was no significant difference in IFN-γ concentration at each time point among the 4 groups ( P>0.05). Conclusion:Intrathecal morphine and fentanyl can increase plasma IFN-γ concentration, and improve peripheral immunosuppression.