Abstract The prevention and control of myopia in Chinese children and adolescents has become a major public health issue. While maintaining increased outdoor activity as a cornerstone intervention, there is an urgent need to explore new complementary approaches that can be effectively implemented in both indoor and outdoor settings. In recent years, environmental spatial frequency has gained increasing attention as one of the key environmental factors influencing the development and progression of myopia. Both animal studies and human research have confirmed that indoor environments lacking mid to high spatial frequency components, often characterized as "visually impoverished", can promote axial elongation and myopia through mechanisms such as disruption of retinal neural signaling, impaired accommodative function, and altered expression of related molecules. Based on the scientific consensus, it is recommended that "enriching of environmental spatial frequency" should be integrated into the myopia prevention and control framework. Following the principles of schoolled organization, family cooperation, community involvement, and student participation, specific measures are put forward in three areas：optimizing school visual settings, improving home spatial environments, and promoting healthy visual behavior. The aim is to create "visually friendly" indoor environments as an important supplement to outdoor activity, thereby providing a novel perspective and strategy for comprehensively advancing myopia prevention and control among children and adolescents.

BACKGROUND:Transcranial magneto-acoustic-electrical stimulation is a novel non-invasive neural regulation technique that utilizes the induced electric field generated by the coupling effect of ultrasound and static magnetic field to regulate the discharge activity of the nervous system.However,the mechanism by which it affects synaptic plasticity in the brain is still not enough. OBJECTIVE:To explore the effect of transcranial magneto-acoustic-electrical stimulation intensity on synaptic plasticity of the prefrontal cortex neural network in mice. METHODS:(1)Animal experiment:Twenty-four C57 mice were equally and randomly divided into four groups:the control group receiving pseudo-stimulation,the 6.35 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,6.35 W/cm2,the 17.36 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,17.36 W/cm2,and the 56.25 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,56.25 W/cm2.The local field potential signals and behavioral correctness were recorded during the execution of T-maze in mice.(2)Modeling and simulation experiments:A neural network model of the prefrontal cortex in mice stimulated by transcranial magneto-acoustic-electrical stimulation was constructed to compare the structural connectivity characteristics of the neural network under different stimulation intensities. RESULTS AND CONCLUSION:Transcranial magneto-acoustic-electrical stimulation could effectively shorten the behavior learning time,improve the working memory ability of mice(P＜0.05),and continue to stimulate the frontal lobe of mice after learning behavior.There was no significant difference in the accuracy of the T-maze behavioral experiment among the experimental groups(P＞0.1).Analysis of local field potential signals in the frontal lobe of mice revealed that transcranial magneto-acoustic-electrical stimulation promoted energy enhancement of β and γ rhythms.As the stimulation intensity increased,there was an asynchronous decrease in β and γ rhythms.Through β-γ phase amplitude coupling,it was found that stimuli could enhance the neural network's ability to adapt to new information and task requirements.Modeling and simulation experiments found that stimulation could enhance the discharge level of the neural network,increase the long-term synaptic weight level,and decrease the short-term synaptic weight level only when the stimulation intensity was high.To conclude,there is a complex nonlinear relationship between different stimulus intensities and the functional structure of neural networks.This neural regulation technique may provide new possibilities for the treatment of related neurological diseases such as synaptic dysfunction and neural network abnormalities.

Objective: To explore the diagnosis, treatment and prognosis of primary prostatic signet ring cell carcinoma (SRCC), so as to provide reference for the clinical diagnosis and treatment. Methods: A retrospective analysis was conducted on the clinical data of 6 patients with primary prostatic SRCC treated in Nanjing Drum Tower Hospital during Nov.2020 and Sep.2024.The clinical manifestations, imaging features, treatment methods, histological characteristics and prognosis were summarized. Results: The average age of the patients was (72.00±4.28) years.Varying degrees of dysuria occurred in 4 patients. All patients underwent multi-parametric magnetic resonance imaging (mpMRI) examination before surgery, and the results indicated typical prostate cancer.Preoperative biopsies showed high-grade (Gleason 8-10) prostate acinar adenocarcinoma.Postoperative pathological diagnoses were mixed types of prostate acinar adenocarcinoma and SRCC, and no metastasis was found in the pelvic lymph nodes.All patients were followed up for 1 to 46 months after surgery and are currently alive.Robot-assisted laparoscopic radical prostatectomy only was performed in 3 cases; apalutamide and leuprolide/triptorelin was administered after surgery in 2 cases; bicalutamide + goserelin was administered after surgery in 1 case, who developed bladder metastasis of prostate cancer 24 months later, and the serum prostate-specific antigen (PSA) concentration decreased to a safe level (<0.2 ng/mL) after the use of darolutamide with radiotherapy.No recurrence or metastasis was found in the remaining patients. Conclusion: Primary prostatic SRCC is a rare and highly aggressive malignant tumor of the prostate.The diagnosis depends on pathological examinations due to lack of specific imaging features and clinical manifestations.The prognosis is poor, and there is currently no standardized treatment.The combined use of surgery, hormonotherapy and radiotherapy can help improve the survival rate of patients.

Objective A non-targeted metabolomics analysis of vitreous fluid from patients with proliferative diabetic retinopathy(PDR)is conducted to explore the"metabolic map"of PDR.This approach aims to deepen the understanding of the disease,identify potential biomarkers.Methods From 35 PDR patients and 30 fresh rhegmatogenous retinal de-tachment(RRD)patients,10 PDR patients with vitreoretinal abnormal adhesions were selected as the experimental group(PDR group),and 10 fresh RRD patients were chosen as the control group(RRD group).Using ultra-high-performance liq-uid chromatography-mass spectrometry non-targeted metabolomics technology,the metabolic profiles of vitreous fluid were analyzed to obtain metabolic spectra.One-dimensional and multidimensional statistical methods were used to analyze the differences in metabolites and metabolic pathways between the PDR and RRD groups.Results A total of 165 differential metabolites were identified in the vitreous humor samples of patients in the PDR and RRD groups,these differential metab-olites were significantly enriched in 21 metabolic pathways(P＜0.05),Among these pathways,those with at least 5 differ-ential metabolites include:methionine and cysteine metabolism;glycine,serine,and threonine metabolism;ascorbic acid and aldose metabolism;amino acid biosynthesis;and central carbon metabolism in cancer.Pyruvate,serine,D-2-phospho-glycerate,threonine,phosphoserine,and high serine are present in multiple metabolic pathways,the areas under the curve are 0.96,0.82,0.85,0.78,0.40,and 0.31,respectively.Conclusion There are 21 significantly different metabolic pathways between PDR and RRD patients.Pyruvate stands out in multiple pathways,potentially serving as a biomarker for PDR diagnosis.

Objective To observe the impact factors of vascular heat sink effect during in vitro microwave ablation(MWA)of porcine lung.Methods Simulation models were established using in vitro porcine lung tissue blocks based on isobaric inflation with an air pump and cyclic perfusion of duck blood with a glass tube and peristaltic pump,etc.MWA was performed under 8 different combining conditions(vessel diameter of 3 or 5 mm,blood perfusion of 30 or 50 cm/s,as well as distance between vessel and ablation antenna of 5 or 10 mm)each for 3 times.The highest temperature TV on vessel side and TC on control side during MWA,and ablation depth DV on vessel side and DC on control side after MWA were recorded.Multi-factor linear regression equations were constructed based on simulated vessel diameters,blood perfusion and distance between vessel and ablation antenna,and the impact factors of|TC-TV|and|DC-DV|were screened,respectively.Results Simulated vessel diameter showed linear positive correlation with both|TC-TV|and|DC-DV|(both P＜0.001).Simulated distance between vessel and ablation antenna showed linear negative correlation with both|TC-TV|and|DC-DV|(both P＜0.001),and the latter had more obvious impact on vascular heat sink effect than the former.Meanwhile,no significant linear relationship was found between simulated blood perfusion and|TC-TV|nor|DC-DV|(both P＞0.05).Conclusion Simulated vessel diameter and distance between vessel and ablation antenna were both impact factors of vascular heat sink effect during in vitro MWA of porcine lung,and the latter was more influential,whereas simulated blood perfusion showed no significant impact on it.

Objective:To analyze the iodine nutrition status and its related factors among adults aged 18 years and above in Zhejiang Province in 2022.Methods:A multistage stratified sampling method was used to select 4 320 adults aged 18 years and above from 16 on-site survey sites in Zhejiang Province for the study. A questionnaire was used to investigate the general demographic information and personal dietary characteristics of the study participants. Household edible salt and urine samples were collected to detect salt iodine content and urinary iodine level by using direct titration and cerium arsenate-catalyzed spectrophotometry, respectively, to evaluate the iodine nutritional status according to the standard. The multiple-ordered logistic regression model was used to analyze the factors influencing the urinary iodine concentration.Results:The age of the 4 320 study participants was (51.19±15.33) years, with males accounting for 44.44% (1 920). About 40.16% of adults (1 735) were from coastal areas and 56.37% (2 435) from urban areas. The salt iodine content, M ( Q1, Q3), of the 4 320 household edible salt samples was 21.10 (0.00, 24.16) mg/kg, including 1 662 non-iodized salt samples, 182 unqualified iodized salt samples and 2 476 qualified iodized salt samples. The rate of iodized salt coverage was 61.53%, and the rate of qualified iodized salt consumption was 57.31%. There was a statistically significant difference in the proportion of qualified iodized salt in adult households among different regions ( P<0.001), with the proportion of non-iodized salt gradually decreasing from coastal to inland areas ( χ 2trend=618.458, P<0.001). The urinary iodine concentration M ( Q1, Q3) was 137.60 (86.85, 210.60) μg/L in 4 320 adult urine samples, with the urinary iodine levels of<100, 100-199, 200-299, and≥300 μg/L accounting for 31.64% (1 367), 40.56% (1 752), 17.66% (763), and 10.14% (438), respectively. There was a nonlinear positive correlation between household salt iodine content and urinary iodine level in adults aged 18 years and above by using the χ 2 test for trend ( χ 2regression=231.10, P<0.001 and χ 2skew=28.81, P<0.001). Urinary iodine concentrations were higher in men than in women ( P=0.029) and higher in adults in rural areas than in urban areas ( P<0.001). There were statistically significant differences in the distribution of iodine nutritional status among adults of different ages, regions, and urban and rural areas (all P<0.001). The proportion of those with urinary iodine levels<100 μg/L gradually increased with age ( χ 2trend=37.493, P<0.001), and gradually decreased from coastal areas to inland areas ( χ 2trend=71.381, P<0.001). The results of the multiple-ordered logistic regression model analysis showed that compared with adults aged 18 to 44 years and male adults, those aged 45 to 59 years and female adults had lower urinary iodine levels, with OR (95% CI) of 0.75 (0.68-0.83) and 0.85 (0.76-0.95), respectively. Compared with adults in coastal and urban adults, those in sub-coastal, inland and rural adults had higher levels of urinary iodine, with OR (95% CI) of 1.89 (1.63-2.19), 2.02 (1.72-2.37) and 1.46 (1.28-1.66), respectively. Conclusion:The overall iodine nutrition level of adults aged 18 years and above in Zhejiang Province in 2022 is generally appropriate. However, there is a potential risk of iodine deficiency among adults in coastal areas.

Objective:To investigate the iodine nutrition status of pregnant women in Zhejiang Province, explore the impact of salt industry system reform on iodine nutrition level of pregnant women, and provide scientific basis for prevention and treatment of iodine deficiency disorders.Methods:From 2016 to 2021, a multi-stage stratified sampling method was used to select 100 pregnant women from 90 counties (cities, districts) in Zhejiang Province each year as survey subjects. Salt samples were collected from pregnant women's families, and one random urine sample was taken for salt iodine and urinary iodine level testing, respectively.Results:A total of 56 581 samples of household edible salt were collected from pregnant women, with a median salt iodine level of 23.20 mg/kg. Among them, 7 961 were non iodized salt, 45 803 were qualified iodized salt, and 2 817 were unqualified iodized salt. The iodized salt coverage rate was 85.93% (48 620/56 581), and the qualified iodized salt consumption rate was 80.95% (45 803/56 581). The proportion of non iodized salt increased from 10.05% (897/8 928) in 2016 to 15.09% (1 461/9 679) in 2021 (χ 2trend = 95.16, P < 0.001). A total of 56 581 urine samples were collected from pregnant women, with a median urinary iodine level of 130.50 μg/L. Among them, the proportions of urinary iodine levels < 150, 150 - 249, 250 - 499, and ≥500 μg/L were 58.32% (32 996/56 581), 27.24% (15 410/56 581), 12.24% (6 926/56 581), and 2.21% (1 249/56 581), respectively. The median urinary iodine level of pregnant women in inland areas was significantly higher than that in coastal areas ( Z = 19.15, P < 0.001). Furthermore, urinary iodine levels exhibited a non-linear decline as age increased (χ 2regression = 12.65, P < 0.001; χ 2partial = 22.65, P < 0.001) and as pregnancy progressed (χ 2regression = 37.28, P < 0.001; χ 2partial = 18.89, P < 0.001). Conclusions:The overall iodine nutrition status of pregnant women in Zhejiang Province is in a state of iodine deficiency (< 150 μg/L), and there is a greater risk in coastal areas compared to inland areas. However, in the context of the reform of the salt industry system, it is still necessary to strengthen the quality supervision of iodized salt, provide scientific iodine supplementation education, promote specialized iodized salt for pregnant women, and strengthen interventions for prevention and control of iodine deficiency disorders.

Objective:To investigate the anemia conditions and characteristics of iron metabolism during different stages of pregnancy in women with different genotypes of thalassemia.Methods:This cohort study selected 3 303 singleton pregnant women who underwent regular prenatal examinations and genetic tests of thalassemia and were delivered at Maternal & Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2019 to December 2023. According to the results of thalassemia gene testing, the women were divided into groups: those without thalassemia genes served as the control group (1 539 cases), and those with thalassemia genes (1 764 cases) were further divided based on genotype into the -α/αα group (326 cases), --/αα or -α/-α group (649 cases), point mutation α-thalassemia group (201 cases), β 0-thalassemia group (368 cases), β +-thalassemia group (91 cases), and α combined with β-thalassemia group (129 cases). Hemoglobin (Hb) and serum ferritin (SF) levels were measured in the first, second, and third trimester of pregnancy. Differences in anemia and iron reserves among the groups at different pregnancy stages were compared using repeated measures analysis of variance, LSD test, Kruskal-Wallis rank-sum test, and Bonferroni correction. Results:Compared to the first trimester, Hb levels decreased in the second and third trimester across all groups (LSD test, all P<0.05), and the severity of anemia increased (Bonferroni correction, all P<0.017). The severity of anemia varied among the groups at the same pregnancy stage ( Hfirst trimester=918.20, Hsecond trimester=1 224.50, Hthird trimester=980.19; all P<0.001), and Hb levels also differed ( Ffirst trimester=282.54, Fsecond trimester=352.31, Fthird trimester=239.02; all P<0.001). The β 0-thalassemia group had higher rates of moderate anemia in the first, second, and third trimester of pregnancy [38.6% (142/368), 85.3% (314/368), and 73.6% (271/368)] compared to other groups (Bonferroni correction, all P<0.002), and lower Hb levels [(102.1±8.9), (92.0±7.3), and (94.6±7.7) g/L] than other groups (LSD test, all P<0.05). As pregnancy progresses, SF levels in each group of pregnant women gradually decreased (LSD test, all P<0.05), and the degree of iron deficiency worsened (Bonferroni correction, all P<0.05). The iron deficiency rate in thalassemia pregnant women during the third trimester ranges from 21.5% (79/368) to 46.0% (150/326). The degree of iron deficiency varies among groups within the same gestational period ( Hfirst trimester=79.13, Hsecond trimester=203.98, Hthird trimester=130.55; all P<0.001), and SF levels also differ ( Ffirst trimester=17.28, Fsecond trimester=44.60, Fthird trimester=31.87; all P<0.001). Among them, the β 0-thalassemia group had the lowest iron deficiency rates in the second, and third trimesters [9.8% (36/368), and 21.5% (79/368)] (Bonferroni correction, all P<0.002). SF levels in the β 0-thalassemia and β +-thalassemia groups were higher than those in other groups during each gestational period (LSD test, all P<0.05). Conclusions:Pregnant women with thalassemia may experience varying degrees of iron deficiency during pregnancy, with the severity of iron deficiency and anemia increasing with gestational age. The degree of iron deficiency and anemia during pregnancy varies among pregnant women with different genotypes of thalassemia. Clinically, individualized management should be provided for pregnant women with thalassemia based on their genotypes, with dynamic monitoring of anemia and iron metabolism changes.

Objective:To investigate the effects of sampling methods on pathological assessment of resected non-small cell lung cancer (NSCLC) specimen with tumor maximum diameter >3 cm after neoadjuvant therapy.Methods:NSCLC patients with a large tumor (diameter >3 cm) that were resected after neoadjuvant therapy from June 2020 to July 2023 were retrospectively collected in the Department of Pathology, Shanghai Pulmonary Hospital, Shanghai, China. Sampling methods of the tumor bed were performed in accordance with the international and Chinese experts recommendations for resection specimens following neoadjuvant therapy (recommended sampling method, RSM), and all remaining tumor bed lesions were completely sampled after recommended sampling (complete sampling method, CSM). The difference of pathological response assessment of residual viable tumor (RVT) between RSM and CSM was examined.Results:A total of 90 cases were identified and analyzed, including 39 cases of squamous cell carcinoma and 51 cases of adenocarcinoma, treated with neoadjuvant therapy including chemotherapy in 22 cases (24.4%), targeted therapy in 14 cases (15.6%), and chemoimmunotherapy in 54 cases (60.0%). There were 62 males and 28 females with an average age of (62.7±17.9) years. The average tumor maximum diameter was 4.3 cm (range, 3.1-8.0 cm). The average number of sampled blocks was 8 blocks (range, 5 to 16) and 15 blocks (range, 8 to 36) per case by RSM and CSM, respectively. According to the definition of major pathological response (MPR) in which RVT is ≤10%, the numbers of patients with MPR were 34 cases by RSM and 30 cases by CSM, respectively. Four cases showed inconsistent RVT between the two methods, including one case of squamous cell carcinoma and three cases of adenocarcinoma. The RVT of the four inconsistent cases was 7%, 7%, 5% and 9% (MPR by RSM), and 15%, 15%, 15% and 20% (non-MPR by CSM), respectively. The kappa values of MPR consistency evaluated by the two sampling methods were 0.893 for all cases, 0.906 for squamous cell carcinoma cases and 0.751 for adenocarcinoma cases. According to MPR cut-off of 65% for invasive primary adenocarcinoma, 24 cases and 20 cases achieved MPR by RSM and CSM, respectively. Of the four inconsistent cases, the RVT by RSM was 60% in three cases and 65% in one case (MPR), whereas the RVT by CSM was 70% in three cases and 75% in one case (non-MPR). The kappa value of the two sampling methods was 0.741.Conclusions:There is high consistency between RSM and CSM in the pathological assessment of post-treatment responses in resected NSCLC specimens with tumor maximum diameter larger than 3 cm. When the percentage of RVT cells is close to MPR, re-evaluation of the specimen is required and CSM may be necessary to accurately evaluate the degree of pathological remission, assist in clinical postoperative treatment, and predict patient prognosis.

Objective:To analyze the iodine nutrition status of children and adolescents and influencing factors in Zhejiang Province, providing scientific basis for optimizing iodine deficiency disorders (IDD) prevention and control strategies.Methods:In June 2022, a multistage stratified sampling method was used to divide 16 counties (cities, districts, abbreviated as counties) in Zhejiang Province into three categories based on their geographical locations (average distance from the coastline): coastal areas (including Dinghai District, Jiaojiang District, Sanmen County, Cixi City and Lucheng District), sub-coastal areas (including Wuxing District, Haining City, Linping District, Fuyang District and Fenghua District), and inland areas(including Suichang County, Changshan County, Shengzhou City, Jindong District, Dongyang City and Yongjia County). One county was selected from each category, and one township (street) was selected from each county. Two administrative villages (neighborhood committees) were selected from each township (street). Ten households including all children and adolescents aged 6-17 in each household were selected from each administrative village (neighborhood committee). Demographic information and personal dietary characteristics were collected via questionnaires, while household salt and a random urine sample were tested for iodine level. Trend analysis was conducted using a χ 2trend test, and a multivariate logistic stepwise regression model was used to analyze the influencing factors of urinary iodine levels. Results:A total of 755 children and adolescents aged 6-17 were selected, including 387 males (51.26%) and 368 females (48.74%), with an age of (11.24 ± 3.32) years. There were 269 children and adolescents in coastal areas (35.63%) and 409 children and adolescents in urban areas (54.17%). A total of 755 household salt samples were collected, with a median salt iodine concentration of 21.80 mg/kg. These included 263 non-iodized salt samples, 38 unqualified iodized salt samples, and 454 qualified iodized salt samples. The coverage rate of iodized salt was 65.17% (492/755), and the consumption rate of qualified iodized salt was 60.13% (454/755). The distribution of salt iodine quality among children and adolescents in different geographical locations showed statistically significant differences (χ 2 = 111.95, P < 0.001), with the proportion of non-iodized salt gradually decreasing from coastal areas to inland areas (χ 2trend = 90.17, P < 0.001). A total of 755 urine samples were collected, with a median urinary iodine concentration of 186.60 μg/L. The proportions of urinary iodine < 100, 100-199, 200-299, and ≥300 μg/L were 16.95% (128/755), 37.62% (284/755), 24.37% (184/755), and 21.06% (159/755), respectively. The χ 2trend test revealed a nonlinear positive correlation between salt iodine level and urinary iodine level (χ 2regression = 21.98, P < 0.001; χ 2partial = 6.96, P < 0.001). The frequency distribution of urinary iodine in children and adolescents from different geographical locations and between urban and rural areas showed statistically significant differences (χ 2 = 29.63, 16.56, P < 0.001). Among them, the proportion of children and adolescents with urinary iodine < 100 μg/L gradually decreasing from coastal areas to inland areas (χ 2trend = 6.15, P = 0.013). The results of multivariate logistic regression analysis revealed that sub-coastal regions, inland regions, and urban-rural regions ( OR = 1.57, 1.53, 1.64, 95% CI: 1.11-2.24, 1.03-2.27, 1.17-2.32, P < 0.05) were significantly associated with urinary iodine levels in children and adolescents aged 6-17. Conclusions:In 2022, the iodine nutrition of children and adolescents in Zhejiang Province is generally suitable, but there is a risk of iodine deficiency among coastal children and adolescents. Geographic location and urban/rural areas are influencing factors on iodine nutrition status of children and adolescents in Zhejiang Province.