Objective To evaluate the radiation dose levels induced by secondary neutrons at different locations inside proton therapy treatment rooms, and analyze the distribution characteristics of neutron energy spectra by combining experimental measurements with simulations, and to provide a theoretical basis and technical support for radiation protection design and management in proton therapy. Methods Multiple representative measurement points were established in the treatment rooms of two hospital-based proton therapy centers. The DIAMON neutron spectrometer was employed to perform in-situ measurements of secondary neutron doses and energy spectra. Three-dimensional simulation models of treatment rooms were constructed using the FLUKA code to simulate the generation and transport of secondary neutrons. Results Measurements showed that the neutron dose was highest near the target region, reaching up to 4293.750 µSv/h. The doses at the maze entrance were the next highest, ranging from 422.091 to 489.268 µSv/h, while the doses in the middle section of the maze ranged from 2.860 to 6.727 µSv/h. The neutron energy spectra exhibited a triple-peak pattern. Conclusion Significant accumulation of secondary neutrons was observed near the target and in the maze regions during proton therapy, with intermediate-energy neutrons being the dominant dose contributor. The consistency between measurements and simulations validated the reliability of the model, which can provide a basis for optimizing treatment room shielding and controlling occupational exposure for staff.

Pre-admission is a critical initiative to optimize medical service processes and alleviate the challenge of "difficult access to healthcare. "However, there is currently a lack of standardized protocols for pre-admission procedures. This study aims to systematically analyze key nodes and risk factors in pre-admission process design and propose optimization strategies, providing a foundation for policy formulation and hospital practices. By constructing a "forward-reverse" dual-process model of pre-admission and identifying risk points based on stakeholder theory (patients, hospitals, healthcare administration, and insurance), the study reveals that while pre-admission can reduce the average length of stay, improve bed turnover rates, and enhance patient satisfaction, it also presents risks such as cross-period financial settlement, challenges in insurance policy adaptability, demands for information system integration, and the need for defining medical safety boundaries. To optimize the pre-admission process and mitigate these risks, this study explores framework improvements in areas including eligibility criteria, mode selection, cost settlement, transition between pre-admission and inpatient status, and cancellation of pre-admission, offering practical guidance for public hospitals. The authors argue that pre-admission requires tripartite collaboration among hospitals, insurers, and healthcare administrations: hospitals should establish top-level design, continuously refine processes, and implement dynamic risk assessment mechanisms; insurance providers should support cross-period settlement policies; and healthcare administrations should issue guiding policies or standardized protocols. Through multi-department coordination and collaborative efforts, the optimization and innovation of pre-admission processes can be advanced, ultimately delivering more efficient and convenient healthcare experiences for patients.

Objective: To comprehensively evaluate and analyze the transfusion outcomes of patients with acute upper gastrointestinal bleeding (UGIB). Methods: The transfusion management system and hospital information system (HIS) were used to retrospectively collect clinical data of 230 patients with UGIB admitted to Zhejiang Provincial People's Hospital and its branches from June 2018 to June 2021. 101 cases were screened and categorized into transfusion group (n=56) and non-transfusion group (n=45) based on transfusion outcomes. The cohort comprised 68 males and 33 females. A univariate model based on the AIMS65 score, a logistic multiple regression model, and multivariate transfusion models using machine learning methods (including Random Forest, Support Vector Machine, and Artificial Neural Network) were established. The sensitivity, specificity, accuracy, and receiver operating characteristic (ROC) curves of each model were compared. Results: For the univariate model based on the AIMS65 scoring, the optimal threshold was 1.5. This model demonstrated a sensitivity of 0.446, a specificity of 0.822, an AUC of 0.67, an accuracy (ACC) of 0.614, a Kappa value of 0.256, and an F1-score of 0.655. For logistics regression model (optimal critical probability: 0.459), the sensitivity was 0.929, specificity was 0.889, AUC was 0.96, ACC was 0.911, Kappa was 0.819, and F1-score was 0.899. For the Random Forest model (optimal critical probability: 0.458), the sensitivity was 0.964, specificity was 0.956, AUC was 0.99, ACC was 0.960, Kappa was 0.920, and F1-score was 0.956. For the Support Vector Machine model (optimal critical probability: 0.474), the sensitivity was 0.875, specificity was 0.933, AUC was 0.94, ACC was 0.901, Kappa was 0.801, and F1-score was 0.894. For the Artificial Neural Network model (optimal critical probability: 0.797), the sensitivity was 0.804, specificity was 0.956, AUC was 0.96, ACC was 0.871, Kappa was 0.745, and F1-score was 0.869. Ten-fold cross validation also confirmed the reliability of the results. Conclusion: Based on integrated various clinical test indicators of patients, we could establish logistic regression model and multiple machine learning models. These models hold significant value for predicting the need for blood transfusion in patients, indicating a promising application prospect for machine learning algorithms in transfusion prediction.

With the widespread application of proton therapy in tumor radiation treatment, the health effects of secondary neutron radiation on patients and medical personnel have become a key concern in radiation protection. Currently, there is no commonly accepted technical standard for neutron dose measurement in proton therapy, making it difficult to compare neutron doses across studies and hindering the standardized development of radiation protection strategies. This paper provides a systematic review of commonly used neutron dose measurement methods and Monte Carlo simulation approaches. This article also explores the key challenges and potential improvements in neutron dose measurement in proton therapy.

Objective:To explore various factors influencing speech recognition ability in patients with age-related hearing loss（ARHL） and to investigate the correlation between speech recognition ability and cognitive function. Methods:This case-control study enrolled 150 ARHL patients（experimental group） and 132 normal-hearing controls. Participants underwent relevant assessments of auditory function, cognitive function, and tinnitus severity. Various statistical analyses were performed to evaluate the results. Results:①The PBmax and MoCA scores were significantly lower in the ARHL group compared to the control group（P<0.05）. ②PBmax in the ARHL group was significantly influenced by multiple factors（P<0.05）. ③Negative correlations were observed between PBmax in the ARHL group and age, degree of hearing loss, duration of the disease, duration of the worst hearing loss, smoking status, and tinnitus severity（P<0.05）, while positive correlations were found between PBmax and education level, occupation type, frequency of verbal communication, and cognitive function level（P<0.05）. ④Higher education level, frequent verbal communication, and high cognitive function level were protective factors for PBmax in ARHL patients（P<0.05）, whereas the other factors were independent risk factors（P<0.05）. ⑤A significant correlation was found between PBmax and MoCA scores in the ARHL group, and this correlation between cognitive function and speech recognition ability remained significant across different degrees of hearing loss（<0.05）. Conclusion:Speech recognition ability in ARHL patients is influenced by multiple factors. Cognitive function demonstrates a robust, bidirectional association with speech recognition ability, even after adjusting for hearing loss severity.
Humans ; Case-Control Studies ; Middle Aged ; Male ; Female ; Aged ; Speech Perception ; Cognition ; Presbycusis/physiopathology* ; Adult ; Hearing Loss

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Objective To investigate and analyze the occupational stress levels and influencing factors among radiation workers in China, and provide a reference for alleviating occupational stress and promoting mental health. Methods Using the general situation questionnaire, Effort-Reward Imbalance questionnaire, and radiation protection knowledge questionnaire, a convenience sampling method was adopted to investigate the occupational stress of 243 radiation workers in Liaoning, Fujian, Guangdong, and Xinjiang provinces. The independent samples t-test, one-way analysis of variance, chi-square test, and binary logistic regression were used to analyze the influencing factors. Results The average score of Effort-Reward Imbalance was 0.97 ± 0.22, and 100 (41.15%) radiation workers had occupational stress. There were significant differences in the detection rate of occupational stress among radiation workers of different ages, working years in radiation positions, monthly incomes, daily sleep durations, and daily working hours (P < 0.05). Logistic regression analysis identified daily working hours as a factor contributing to occupational stress. Conclusion The occupational stress among radiation workers in China is relatively severe. It is recommended to pay attention to the associated risks and implement targeted intervention measures to reduce the impact of occupational stress.

Objective To investigate the association between the variability of remnant cholesterol inflammatory index(RCII),a novel composite biomarker,and the risk of stroke,in order to provide a theoretical basis for stroke prevention.Methods A prospective cohort study was conducted on 38 659 Kailuan individuals who took annual physical examinations in 2006,2008,and 2010.These subjects were grouped based on the quartiles of RCII variability,which was represented by standard deviation(SD)and average real variability(ARV),and were followed up every 2 years,with the occurrence of stroke(including ischemic and hemorrhagic strokes),death,or the end of follow-up on December 31,2022 as the endpoints.Kaplan-Meier method was used to calculate the cumulative incidence rate of endpoint events across different groups,and log-rank test was used to compare the difference of cumulative incidence of endpoint events in each group.Multivariate Cox proportional hazards regression model was adopted to analyze the association between RCII variability and risk of stroke.Results Among the 38 659 participants,a total of 2 539 strokes occurred during a mean follow-up period of 11.22±2.26 years.After adjusting confounding factors,when the participants were grouped by the quartiles of RCII-SD,the hazard ratio(HR)for stroke was 1.034(95%CI:0.917～1.167,P=0.584),1.146(95%CI:1.018～1.290,P=0.025),and 1.209(95%CI:1.066～1.370,P=0.003),respectively in the Q2,Q3,and Q4 groups,when compared with the Q1 group(Ptrend<0.05).When they were grouped by the quartiles of RCII-ARV,the HR for stroke was 1.008(95%CI:0.894～1.136,P=0.901),1.109(95%CI:0.986～1.248,P=0.085),and 1.152(95%CI:1.018～1.303,P=0.025),respectively,in the Q2,Q3,and Q4 groups,when compared with the Q1 group.Furthermore,both sensitivity and stratified analyses yielded similar results.Conclusion RCII variability is significantly associated with stroke,and the risk of stroke is gradually increasing with increment of the variability.Countermeasures Relevant authorities can focus on reducing RCII variability as a central objective by establishing regular monitoring mechanism,strengthening lifestyle interventions,and standardizing dietary,exercise,and weight management in order to suppress the index fluctuations.The principle of stable lipid-lowering in medication and optimization of therapeutic regimens with stable efficacy should be emphasized to prevent the risk of additional vascular damage.

OBJECTIVE: To investigate the clinical phenotype and genetic diagnosis process of fetuses with 21 hydroxylase deficiency (21-OHD) caused by compound heterozygous variant of the CYP21A2 gene . METHODS: A fetus who was diagnosed at Taizhou Hospital in Zhejiang Province on December 4, 2020 due to unclear characteristics of external genitalia on ultrasound was selected as the study subject. Chromosome copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were performed on amniotic fluid samples. Candidate variants were validated by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA), and short tandem repeat (STR) analysis was used to exclude maternal blood contamination. The pathogenic mechanism of the variants was further explored. The procedure followed by this study was approved by the Medical Ethics Committee of Taizhou Hospital (Ethics No.: K20201009). RESULTS: The MRI examination of the fetal external genitalia showed thickening of labia minora and enlargement of the clitoris. The CNV-seq results of the fetus showed no significant abnormality. The WES results showed that the fetus had a homozygous c.293-13C>G variant in the CYP21A2 gene (NM-000500.9). STR testing excluded maternal blood contamination. Sanger sequencing verified the presence of heterozygous c.293-13C>G variant of the CYP21A2 gene in the fetus and its mother, while its father did not detect this mutation. Further MLPA testing results showed that the fetus and its father had heterozygous deletion (I2G-C locus) mutations in exon 1~7 of the CYP21A2 gene. Based on the "Standards and Guidelines for Interpretation of Sequence Variants" jointly developed by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), both variants of the CYP21A2 gene carried by the fetus were predicted to be pathogenic. According to the imaging and genetic testing results of the external genitalia of the fetus, the fetus was prenatally diagnosed as 21-OHD caused by the CYP21A2 gene variant. Follow-up after prenatal diagnosis showed that the couple had opted to terminate the pregnancy at a local hospital at 31⁺ weeks of gestation, and the clinical phenotype of the abortion fetus was consistent with the imaging and molecular genetic diagnosis. CONCLUSION The imaging features of this fetus are suspected to be congenital adrenal hyperplasia (CAH). Combined with WES, Sanger sequencing, and MLPA testing results, the fetus was diagnosed with 21-OHD caused by compound heterozygous variants of the CYP21A2 gene, which provided a basis for prenatal diagnosis.
Humans ; Steroid 21-Hydroxylase/genetics* ; Female ; Pregnancy ; Adrenal Hyperplasia, Congenital/diagnosis* ; Heterozygote ; Prenatal Diagnosis/methods* ; Adult ; Fetus ; DNA Copy Number Variations ; Mutation ; Genetic Testing

OBJECTIVE: To investigate the clinical characteristics and genetic etiology of a male with a normal phenotype and SRY gene-positive 46,XX/46,XY tetrazoospermia chimerism. METHODS: A male patient with an abnormal peripheral blood chromosomal karyotype detected at the Infertility Center of Taizhou Hospital of Zhejiang Province on December 2, 2013 was selected as the study subject. Peripheral venous blood samples were collected from the proband and his family members, together with a semen sample from the proband. Chromosomal karyotype analysis, red blood cell blood group identification, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH), sex-determining region Y (SRY) gene detection, and short tandem repeat (STR) microsatellite marker analysis were performed on the peripheral venous blood sample from the proband. Routine semen analysis, sperm FISH, and STR testing were also conducted. STR verification was performed on both parents. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: k20201009). RESULTS: The proband, a 37-year-old male, had normal secondary sexual characteristics and external genitalia development. The chromosomal karyotype of his peripheral blood sample was 46,XX[94]/46,XY[6]. ABO blood group typing was positive for Rh(D) type O and negative for Rh(D) type A, indicating the presence of two red blood cell populations. CMA result was arr[GRCh37](1-22)×2,(XX)×1. Autosomal and X chromosome SNP genotypes were BB-BB, AB-AB, and AA-AA, making it impossible to identify homozygous/heterozygous chimerism. FISH detection of interphase nuclei showed nuc ish XX[92]/XY[8]. Testing of the SRY gene was positive. STR analysis showed a single X peak (no Y peak) at the AMEL locus, 10/12 at the Penta D locus, and no third allele at other loci. Routine semen analysis were normal. Sperm FISH detection showed haploid nuclei nuc ish X[53]/Y[47]. Sperm STR analysis revealed an X/Y bimodal distribution at the AMEL locus and a 9/14 distribution at the Penta D locus, with no third allele observed at other loci. Above results suggested that the proband's blood and germ cell lines had originated from a heterozygous chimera formed by the fusion of two different zygotes. CONCLUSION Combined genetic techniques confirmed that the proband's peripheral blood AMEL genotype is X/X, while the sperm is X/Y. The Penta D locus showed a bi-allelic heterozygous pattern of 10/12 in the peripheral blood sample and 9/14 in the sperm sample, suggesting that the proband is a tetrazygotic chimera resulted from the fusion of 46,XX/46,XY zygotes.
Humans ; Male ; Adult ; Chimerism ; Microsatellite Repeats ; Sex-Determining Region Y Protein/genetics* ; Phenotype ; Genes, sry ; In Situ Hybridization, Fluorescence ; Karyotyping