The industry standard Barium Sulfate Anti-Radiation Mortar (JC/T 2676—2022) was officially released on September 30, 2022, and came into effect on April 1, 2023. The promulgation and implementation of this standard play a significant role in improving the product quality of barium sulfate anti-radiation mortar, promoting industry development, and safeguarding the occupational health of workers. To facilitate accurate understanding of the standard clauses and ensure proper implementation of its requirements, this article elaborated on the background, objectives, and significance of the standard development, along with an interpretation of its key clauses.

Objective: This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) with cisplatin single-agent chemotherapy vs. CCRT with cisplatin combined with paclitaxel dualagent therapy. The primary outcomes are overall survival (OS), progression-free survival (PFS), local recurrence (LR), distant metastasis (DM) and the occurrence of adverse events. Methods: This retrospective cohort study included patients with FIGO 2009 stage IB1-IVA cervical squamous cell carcinoma undergoing radical CCRT. Patients were divided into groups A and B, treatment outcomes were compared between the two groups after 1:1 proportional propensity score matching. Results: Medical records of 1,203 patients were reviewed and 572 patients were finally included for propensity score matching. After propensity score matching, 121 pairs of patients were selected for analysis. The OS, PFS, LR and DM rates were 78.5% and 83.5% (p=0.417), 73.3% and 78.5% (p=0.312), 6.6% and 2.5% (p=0.123), 19% and 15.7% (p=0.497) for groups A and B, respectively. Further subgroup analysis according to stage and lymph node metastatic status showed no difference in survival between the two groups. The incidence of grade 3–4 acute haematological toxicities was different between the two groups (p<0.05). Conclusion Cisplatin combined with paclitaxel CCRT couldn’t improve the survival rates of patients with LACC. However, the hematological toxicity of combination chemotherapy is more severe but controllable. Cisplatin single-agent therapy remains the first choice for CCRT. Further prospective studies are indicated to provide evidence for the efficacy of cisplatin plus paclitaxel in dual-agent concurrent therapy.

Isocitrate dehydrogenase(IDH)wild-type glioma is a type of highly invasive brain tumor with poor prognosis and a high recur-rence rate.The recurrence process is driven by multiple complex and interwoven factors.Although the current standard treatment regi-mens can temporarily alleviate patients'symptoms,they still face significant challenges in effectively preventing tumor recurrence.The re-currence mechanism of this tumor is intricate and covers multiple aspects such as genomic instability,maintenance of stem cell characterist-ics and mesenchymal transformation,as well as dynamic changes in the tumor microenvironment.This article aims to comprehensively sum-marize the recurrence mechanism of glioblastoma and deeply explore potential countermeasures targeting these mechanisms,hoping to open up new perspectives and approaches for the treatment of recurrent tumors.

Objective:To investigate the clinical features and pathogenesis of a child with Stargardt disease caused by variants of ABCA4 gene. Methods:A child presented at Shenzhen Eye Hospital between September 5, 2020, and April 3, 2023 was selected as the study subject. Clinical data of the child were collected. Whole exome sequencing was performed on peripheral blood samples from the child and his parents. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (Ethics No.: 2022KYPJ072).Results:The child was a 10-year-old male presenting with uncorrected visual acuity of 0.1 in both eyes without improvement with refractive correction. Fundus photography showed diffusely distributed yellow-white flecks in the macular region. FAF revealing central hypofluorescence surrounded by a hyperfluorescent ring, and OCT demonstrating significant foveal thinning (right eye: 45 μm; left eye: 50 μm) with ellipsoid zone disruption. Whole exome sequencing and Sanger sequencing revealed that the child has harbored compound heterozygous variants of the ABCA4 gene, namely c. 2384G>T (p.Gly795Val) and c. 2903G>A (p.Arg968Glu), which were inherited from his phenotypically normal parents and consistent with an autosomal recessive inheritance. This specific combination of the variants was previously unreported. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were classified as likely pathogenic (PM2_Supporting+ PM3+ PP3+ PP4; PM1+ PM2_Supporting+ PP3+ PP4). Conclusion:The novel compound heterozygous variants of the ABCA4 gene probably underlay the genetic etiology of Stargardt disease type 1 in this child. Above finding has expanded the mutational spectrum of the ABCA4 gene among the Chinese population and provided further evidence for understanding the genetic heterogeneity and genotype-phenotype correlation of the Stargardt disease.

Objective:To explore the relationship between obesity indicators and DNA methylation clocks acceleration,and to analyze their temporal sequence.Methods:Data were obtained from two sur-veys conducted in 2013 and 2017-2018 by the Chinese National Twin Registry.Peripheral blood DNA methylation data were measured using the Illumina Infinium Human Methylation 450K BeadChip and EPIC BeadChip.DNA methylation clocks/acceleration metrics(GrimAA,PCGrimAA and Dunedin-PACE)were calculated using the DNA methylation online tool(https://dnamage.genetics.ucla.edu/)or R code provided by researchers.Obesity indicators included weight,body mass index(BMI),waist circumference,waist-hip ratio,and waist-height ratio.A total of 1 070 twin individuals were included in the cross-sectional analysis,comprising 378 monozygotic(MZ)twin pairs and 155 dizygotic(DZ)twin pairs for within-pair analysis.Mixed-effects models were used to examine the associations between obesity indicators and DNA methylation clocks,as well as their acceleration measures.The longitudinal analysis included 314 twin individuals,comprising 95 MZ twin pairs and 62 DZ twin pairs for within-pair analy-sis.Cross-lagged panel models were applied to further explore the temporal relationships between obesity and DNA methylation clock indicators.All analyses were conducted both in the full twin sample and separately within MZ and DZ twin pairs.Results:In the cross-sectional analysis population,monozygotic twins accounted for 71.0％,males for 68.0％,and the mean chronological age was(49.9±12.1)years.In the longitudinal analysis population,monozygotic twins accounted for 60.5％,males for 60.8％,with a mean baseline chronological age of(50.4±10.2)years and a mean follow-up duration of(4.6±0.6)years.Except for the waist-to-hip ratio,which was significantly higher at follow-up com-pared with baseline,no statistically significant differences were observed in the means of other obesity in-dicators between baseline and follow-up.Correlation analysis revealed that weight,BMI,waist circumfe-rence,waist-hip ratio(WHR),and waist-height ratio(WHtR)were positively correlated with Dunedin-PACE in all the twins,with WHtR showing the strongest association(β=0.21,95％CI:0.11 to 0.31).Weight and BMI were negatively associated with GrimAA(β=-0.03,95％CI:-0.05 to-0.01;β=-0.07,95％CI:-0.12 to-0.02),while weight was negatively associated with PCGrim-AA(β=-0.02,95％CI:-0.03 to 0.00).However,within-twin-pair analyses showed no statistically significant correlations.Cross-lagged panel model analysis indicated that higher baseline weight might lead to increased GrimAA at follow-up,while elevated baseline weight,BMI,and waist circumference might increase PCGrimAA.Higher baseline WHR was associated with increased DunedinPACE at follow-up.Conclusion:Obesity indicators correlate with DNA methylation clock acceleration metrics.Baseline obesity may influence changes in certain DNA methylation clock indicators over time,suggesting that obesity could exert long-term health effects by accelerating DNA methylation aging.However,these associations may be confounded by shared genetic or environmental factors among the twins.

OBJECTIVE: To investigate the clinical features and pathogenesis of a child with Stargardt disease caused by variants of ABCA4 gene. METHODS: A child presented at Shenzhen Eye Hospital between September 5, 2020, and April 3, 2023 was selected as the study subject. Clinical data of the child were collected. Whole exome sequencing was performed on peripheral blood samples from the child and his parents. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (Ethics No.: 2022KYPJ072). RESULTS: The child was a 10-year-old male presenting with uncorrected visual acuity of 0.1 in both eyes without improvement with refractive correction. Fundus photography showed diffusely distributed yellow-white flecks in the macular region. FAF revealing central hypofluorescence surrounded by a hyperfluorescent ring, and OCT demonstrating significant foveal thinning (right eye: 45 μm; left eye: 50 μm) with ellipsoid zone disruption. Whole exome sequencing and Sanger sequencing revealed that the child has harbored compound heterozygous variants of the ABCA4 gene, namely c.2384G>T (p.Gly795Val) and c.2903G>A (p.Arg968Glu), which were inherited from his phenotypically normal parents and consistent with an autosomal recessive inheritance. This specific combination of the variants was previously unreported. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were classified as likely pathogenic (PM2_Supporting+PM3+PP3+PP4; PM1+PM2_Supporting+PP3+PP4). CONCLUSION The novel compound heterozygous variants of the ABCA4 gene probably underlay the genetic etiology of Stargardt disease type 1 in this child. Above finding has expanded the mutational spectrum of the ABCA4 gene among the Chinese population and provided further evidence for understanding the genetic heterogeneity and genotype-phenotype correlation of the Stargardt disease.
Humans ; Male ; Child ; ATP-Binding Cassette Transporters/genetics* ; Stargardt Disease/genetics* ; Heterozygote ; Mutation ; Exome Sequencing ; Macular Degeneration/congenital*

Objective:To analyze the data changes of tertiary hospitals,secondary hospitals and primary healthcare institutions in Shandong before and after the reform of Dignosis Related Group(DRG)/Diagnosis-Intervention Packet(DIP)payment method,and to explore the impact of the reform of DRG/DIP payment method on the effect of hierarchical diagnosis and treatment.Methods:Data were collected from 16 cities in Shandong Province for a total of 18 quarters in the first half of 2019-2023,including the percentage of expenditure of the health insurance fund,the percentage of discharges,and the sub-average hospitalization cost.Spatial panel models were constructed to conduct σ-convergence and absolute β-convergence analyses.Results:The convergence analysis showed that the inter-regional differences in the percentage of discharges,the percentage of fund expenditure and the average hospitalization cost of tertiary medical institutions were reduced;the regression coefficients of the three indicators in the absolute convergence analysis were significantly negative(β＜0,P＜0.01),indicating that the level of hierarchical diagnosis and treatment in various cities and regions has been equalized.Conclusion:The reform of DRG/DIP payment method reform has effectively optimized the allocation of medical resources in Shandong and reduced regional differences.It is needed to strengthen the effect of the payment method reform,reinforced the incentive of primary care and construct a full-cycle health management-oriented health insurance system in the future.

Objective To explore the relationship between hemorheology and Carotid Atherosclerosis.Methods The clinical data of 153 patients who underwent both hemorheological testing and carotid artery ultrasound were divided into a CAS group(n=96)and a non-CAS group(n=57)based on ultrasound findings.Clinical data and laboratory indicators were compared between two groups.Multivariate logistic regression analysis was used to explore the influencing factors of CAS.The ROC curves graph were drawn to observe the role of hemorheological indicators in predicting CAS and select the optimal cutoff value based on the maximum Youden index.Results The CAS group demonstrated higher levels in age,BMI,RBC aggregation index,low&high shear reduced viscosity of whole blood,plasma viscosity and fibrinogen compared to the non-CAS group(P<0.05).The multivariate logistic regression analysis showed that plasma viscosity(OR=38.270,95%CI:1.206～1214.508),age(OR=1.119,95%CI:1.065～1.176)were risk factors for the occurrence of CAS(P<0.05).The ROC curves showed that the area under the curve(AUC)of plasma viscosity and age were 0.623、0.728.Conclusion CAS patients have high levels of plasma viscosity and advanged age compared to the patient without CAS.Elevated plasma viscosity and age is a risk factor for CAS,with plasma viscosity≥1.46 mPa·s,over the age of 56.5 as a significant value for predicting CAS.

Objective: This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) with cisplatin single-agent chemotherapy vs. CCRT with cisplatin combined with paclitaxel dualagent therapy. The primary outcomes are overall survival (OS), progression-free survival (PFS), local recurrence (LR), distant metastasis (DM) and the occurrence of adverse events. Methods: This retrospective cohort study included patients with FIGO 2009 stage IB1-IVA cervical squamous cell carcinoma undergoing radical CCRT. Patients were divided into groups A and B, treatment outcomes were compared between the two groups after 1:1 proportional propensity score matching. Results: Medical records of 1,203 patients were reviewed and 572 patients were finally included for propensity score matching. After propensity score matching, 121 pairs of patients were selected for analysis. The OS, PFS, LR and DM rates were 78.5% and 83.5% (p=0.417), 73.3% and 78.5% (p=0.312), 6.6% and 2.5% (p=0.123), 19% and 15.7% (p=0.497) for groups A and B, respectively. Further subgroup analysis according to stage and lymph node metastatic status showed no difference in survival between the two groups. The incidence of grade 3–4 acute haematological toxicities was different between the two groups (p<0.05). Conclusion Cisplatin combined with paclitaxel CCRT couldn’t improve the survival rates of patients with LACC. However, the hematological toxicity of combination chemotherapy is more severe but controllable. Cisplatin single-agent therapy remains the first choice for CCRT. Further prospective studies are indicated to provide evidence for the efficacy of cisplatin plus paclitaxel in dual-agent concurrent therapy.

Objective: To investigate the inhibitory effect of Elesclomol (ES) + Cu2 + on the proliferation of human hepatoma cell lines PLC/PRF/5 and Huh-7 and its potential to induce Cuproptosis. Methods: Human hepatoma cell lines PLC/PRF/5 and Huh_7 cells were Cultured in vitro. ES solution , Cu2 + solution and copper chelating agent ammonium tetrathiomolybdate VI (ATTM) solution was treated separately or in combination. The effect of ES + Cu2 + on the survival rate of human hepatoma cell lines PLC/PRF/5 and Huh_7 cells and the effect of ES + Cu2 + on the survival rate after pretreatment with copper chelating agent ATTM were evaluated using CCK_8 kit. The cell death induced by ES + Cu2 + was detected by flow cytometry and the changes of ES + Cu2 + after pretreatment with copper chelating agent ATTM. The expression of Cuproptosis related proteins ATPase copper transporting beta (ATP7B) ,ferredoxin 1 (FDX1) , dihydrolipoamide s_acetyltransferase(DLAT) and superoxide dismutase 1 (SOD1) were detected by Western blot. The effect of ES + Cu2 + on cell proliferation and the reverse effect after ATTM pretreatment was detected by cell scratch assay. Results: The toxicity of ES + Cu2 + to human hepatocellular carcinoma cell lines PLC/PRF/5 and Huh_7 was significantly dose_dependent (P < 0. 05) . Compared with the control group , the combined application of ES and Cu2 + had a more significant inhibitory effect on hepatocellular carcinoma cells than ES or Cu2 + alone (P < 0. 05) , and copper chelating agent ATTM could reverse the inhibitory effect of ES + Cu2 + on hepatocellular carcinoma cells (P < 0. 05) . Flow cytometry results showed that compared with the control group , the proportion of cell death in PLC/PRF/5 and Huh_7 cells treated with ES + Cu2 + increased , while the proportion of cell death decreased after ATTM intervention (P < 0. 05) . The results of cell scratch test showed that the migration ability of PLC/PRF/5 and Huh_7 cells was decreased after ES + Cu2 + treatment , however, the addition of ATTM reversed the inhibitory effect of ES + Cu2 + on cell migration (P < 0. 05) . Compared with the control group , the expression levels of copper death related proteins ATP7B , FDX1 , DLAT and SOD1 decreased after ES + Cu2 + treatment , but the addition of ATTM reversed the expression trend of these proteins (P < 0. 05) . Conclusion The combination of ES and Cu2 + can effectively inhibit the proliferation and migration of PLC/PRF/5 and Huh_7 of hepatocellular carcinoma cells , and induce Cuproptosis , which provides a new strategy for the treatment of hepatocellular carcinoma.