Objective:To explore effect and potential mechanism of disulfiram on necrotizing apoptosis of renal podocytes and macrophages.Methods:Mouse renal podocyte MPC-5 and macrophages J774A.1 and BMDM cells were cultured in vitro and treated with TNF-α,Smac mimetic LCL-161 and pan-caspase inhibitor IDN-6556(TSI)to induce necroptosis.Cell necrosis was detected by propi-dium iodide staining.Western blot was used to detect protein levels of necroptosis markers MLKL,RIPK3 and RIPK1.Immuno-fluorescence microscopy was used to observe the subcellular distribution of RIPK3 and p-MLKL in MPC-5 cells.Results:TSI treat-ment induced significant necroptosis in both MPC-5 cells and macrophages.Disulfiram was able to inhibit necroptosis in these cells in a dose-dependent manner.Moreover,disulfiram markedly blocked the phosphorylation of RIPK1,RIPK3 and MLKL.The aggregation of RIPK3 and p-MLKL were also suppressed by disulfiram.Conclusion:Disulfiram inhibits necroptosis in podocytes and macrophages by suppressing RIPK1/RIPK3/MLKL signaling pathway.

Objective:To investigate the clinical characteristics and genetic etiology of fetal Dandy-Walker spectrum (DWS) anomalies.Methods:This retrospective cohort study analyzed 28 fetuses with ultrasonographically confirmed DWS (ten classic Dandy-Walker malformations and 18 Dandy-Walker variants) at the First Affiliated Hospital, Zhengzhou University from January 2019 to June 2024. All cases underwent systematic ultrasonographic evaluation. Genetic analyses included chromosomal karyotyping alone ( n=4) or combined with copy number variation sequencing (CNV-seq) ( n=10). Descriptive statistics and Chi-square tests (or Fisher's exact test) with Bonferroni correction were applied. Results:(1) Among 28 fetuses, seven (25.0%) had isolated DWS and 21 (75.0%) non-isolated DWS. Central nervous system anomalies were most common (53.6%, 15/28). (2) Karyotyping identified abnormalities in four cases (4/14), including two triploidies, one case of mosaicism for a derivative chromosome der(1;10), and one 17p deletion. CNV-seq detected anomalies in six cases (25.0%, 6/24), four of which were missed by karyotyping: 3q23 deletion (encompassing ZIC1/ ZIC4), 13q11 duplication, and other critical variants. (3) Combined testing yielded a higher detection rate (28.6%, 8/28) than karyotyping alone (4/14, χ2=4.62, P=0.032) or CNV-seq alone (25.0%, 6/24, χ2=4.83, P=0.028) ( P=0.048 and 0.044 after Bonferroni correction). Conclusions:DWS demonstrates significant genetic heterogeneity, primarily involving chromosomal numerical anomalies (e.g., triploidy) and copy number variations (e.g., 3q23 deletion). Combined karyotyping and CNV-seq improves detection rates of genetic abnormalities.

Objective:To explore effect and potential mechanism of disulfiram on necrotizing apoptosis of renal podocytes and macrophages.Methods:Mouse renal podocyte MPC-5 and macrophages J774A.1 and BMDM cells were cultured in vitro and treated with TNF-α,Smac mimetic LCL-161 and pan-caspase inhibitor IDN-6556(TSI)to induce necroptosis.Cell necrosis was detected by propi-dium iodide staining.Western blot was used to detect protein levels of necroptosis markers MLKL,RIPK3 and RIPK1.Immuno-fluorescence microscopy was used to observe the subcellular distribution of RIPK3 and p-MLKL in MPC-5 cells.Results:TSI treat-ment induced significant necroptosis in both MPC-5 cells and macrophages.Disulfiram was able to inhibit necroptosis in these cells in a dose-dependent manner.Moreover,disulfiram markedly blocked the phosphorylation of RIPK1,RIPK3 and MLKL.The aggregation of RIPK3 and p-MLKL were also suppressed by disulfiram.Conclusion:Disulfiram inhibits necroptosis in podocytes and macrophages by suppressing RIPK1/RIPK3/MLKL signaling pathway.

Objective:To investigate the clinical characteristics and genetic etiology of fetal Dandy-Walker spectrum (DWS) anomalies.Methods:This retrospective cohort study analyzed 28 fetuses with ultrasonographically confirmed DWS (ten classic Dandy-Walker malformations and 18 Dandy-Walker variants) at the First Affiliated Hospital, Zhengzhou University from January 2019 to June 2024. All cases underwent systematic ultrasonographic evaluation. Genetic analyses included chromosomal karyotyping alone ( n=4) or combined with copy number variation sequencing (CNV-seq) ( n=10). Descriptive statistics and Chi-square tests (or Fisher's exact test) with Bonferroni correction were applied. Results:(1) Among 28 fetuses, seven (25.0%) had isolated DWS and 21 (75.0%) non-isolated DWS. Central nervous system anomalies were most common (53.6%, 15/28). (2) Karyotyping identified abnormalities in four cases (4/14), including two triploidies, one case of mosaicism for a derivative chromosome der(1;10), and one 17p deletion. CNV-seq detected anomalies in six cases (25.0%, 6/24), four of which were missed by karyotyping: 3q23 deletion (encompassing ZIC1/ ZIC4), 13q11 duplication, and other critical variants. (3) Combined testing yielded a higher detection rate (28.6%, 8/28) than karyotyping alone (4/14, χ2=4.62, P=0.032) or CNV-seq alone (25.0%, 6/24, χ2=4.83, P=0.028) ( P=0.048 and 0.044 after Bonferroni correction). Conclusions:DWS demonstrates significant genetic heterogeneity, primarily involving chromosomal numerical anomalies (e.g., triploidy) and copy number variations (e.g., 3q23 deletion). Combined karyotyping and CNV-seq improves detection rates of genetic abnormalities.

ObjectiveTo investigate the distribution of vascular cognitive impairment （VCI） with kidney Yang deficiency syndrome and explore the biological nature of VCI with kidney Yang deficiency syndrome from the perspective of DNA methylation under the combination of disease and syndrome， so as to provide an epigenetic target for traditional Chinese medicine （TCM） treatment of this disease with this syndrome in the future. MethodCommunity residents in Beijing were screened out for cognitive impairment from September 2020 to November 2022 through the scale， and VCI patients were analyzed for the syndrome. VCI patients with kidney Yang deficiency syndrome and healthy people were enrolled in this study. Peripheral venous blood was collected and subjected to genome-wide DNA methylation detection by Illumina Human Methylation 850K BeadChip. Then， differentially methylated genes （DMGs） were screened out for bioinformatics analysis. ResultA total of 1 902 people were investigated in this study， and 201 of them had VCI， accounting for 10.57%， including 72.14% with kidney Yang deficiency syndrome. The methylation results showed that compared with the normal group， the VCI group had 386 differential methylation sites， and 136 DMGs were annotated. The Kyoto Encyclopedia of Gene and Genomes（KEGG） signaling pathway enrichment analysis showed that the DMGs between the two groups were mainly involved in mammalian target of rapamycin（mTOR） signaling pathway， Estrogen signaling pathway， cyclic adenosine monophosphate（cAMP） signaling pathway， etc. Protein-protein interaction （PPI） analysis showed that DMGs， such as epidermal growth factor receptor（EGFR）， epidermal growth factor （EGF）， and signal transducer and activator of transcription 3（STAT3）， played important roles in the network. ConclusionKidney Yang deficiency is the main syndrome in VCI patients. DMGs including EGFR， EGF， and STAT3 and the related pathways such as mTOR signaling pathway， Estrogen signaling pathway， and cAMP signaling pathway may play a vital role in the occurrence and development of VCI with kidney Yang deficiency syndrome.

Diabetic cardiomyopathy refers to dysfunction of cardiac muscle in patients with diabetes that cannot be directly ascribed to hypertension， coronary heart disease or other defined cardiac abnormalities. Imbalance in metabolic flexibility is the underlying cause of diabetic cardiomyopathy， which is manifested as distorted nutrient sensing， slow substrate switching， and impaired energy homeostasis. In the case of diabetes/insulin resistance， cardiac fatty acid oxidation increases while glucose oxidation decreases， resulting in the imbalance in cardiac metabolic flexibility. Thus， the heart fails to switch substrates depending on the changes （taking food/fasting， rest/exercise） and the energy production in cardiomyocytes reduced， causing cardiac dysfunction. Moreover， the excessive cardiac fatty acid fails to be degraded by the mitochondrial β oxidation， triggering cardiac lipid accumulation and reduction in glucose oxidation. Therefore， the glucose in the pentose phosphate （PPP） and the hexosamine biosynthetic pathway （HBP） increases and the production of advanced glycation end products rises， inducing glycolipotoxicity. The intermediates of abnormal substrate metabolism cause oxidative stress， inflammation， mitochondrial dysfunction and further result in impaired myocardial function. Qi and blood are the main functional substances for the normal functioning of the body. Qi and blood harmonize and work together to defend against external pathogen， while disharmony of blood and Qi will induce the production of various pathological products that lead to the occurrence of diseases. The function and regulation of Qi-Blood movement are similar to those of metabolism. Qi deficiency and blood stasis， Qi stagnation and blood stasis， and other "blood-Qi disharmony" types run through the whole process of diabetic cardiomyopathy， and "blood-Qi disharmony" will affect systemic substrate metabolism and lead to impaired energy metabolism. By systematically explaining the relationship between "blood-Qi disharmony" and "metabolic flexibility" in diabetic cardiomyopathy， we provide scientific research and clinical formulation ideas for targeting "metabolic flexibility" in the prevention of diabetic cardiomyopathy with Qi-replenishing and Blood-activating medicinals.

Objective: To explore the consumption of sugar sweetened beverages (SSBs) and its association with behavioral problems in Chinese preschool children, and to provide a scientific basis for the prevention of behavioral problems of children. Methods: A total of 7 634 children aged 3-6 years were chosen from kindergartens in 3 cities (Yangzhou, Xuzhou, Zhenjiang) in the lower reaches of Yangtze River using method of cluster sampling during October to November in 2017. Parental or guardian questionnaires were used to obtain information regarding child consumption of SSBs. The Strengths and Difficulties Questionnaire (SDQ) was used to assess children s emotional and behavioral problems. Multivariate Logistic regression model was used to explore the association between different SSBs intake frequency and children s behavioral problems. Results: A total of 5 509(72.2%) consumed SSBs less than once a day, 830(10.9%) reported SSBs consumption once a day, and 1 295(16.9%) had 2 times or more intake of sugar sweetened beverages per day. After adjusting for confounding factors including age, sex, BMI, family financial status, parental education, screen time, sleep duration, and physical activities duration, multiple Logistic regression model revealed that intake of SSBs once a day was associated with an increased risk of hyperactivity disorder ( OR =1.26, 95% CI =1.01-1.57) and SDQ total difficulties ( OR =1.44, 95% CI =1.14-1.82) in boys and with an increased risk of emotional symptoms ( OR=1.34, 95%CI =1.02-1.76), conduct problems ( OR=1.53, 95%CI =1.18-2.00), hyperactivity disorder ( OR=1.79, 95%CI =1.42-2.27) and prosocial behavior ( OR=1.48, 95%CI =1.14-1.91) in girls. Intake of SSBs≥2 times per day was associated with an increased risk of emotional symptoms ( OR=1.28, 95%CI =1.02-1.59) and SDQ difficulties ( OR=1.30, 95%CI =1.07-1.58) in boys and not with behavioral problems in girls. Conclusion Sex differences are observed with respect to the association between SSBs intake and behavioral problems in preschoolers, but no significant dose response relationship was observed. More longitudinal studies are needed to further explore the association between SSBs intake and behavioral problems in preschool children as well as the underlying physiological mechanisms in future.

Objective: Based on observational, longitudinal and intervention study of common diseases among students in Jiangsu Province, this paper presents the current progress of two year follow up of myopia cohort regarding the association between growth parameters with progression of myopia among children and adolescents in areas with rapid economic growth. Methods: This survey adopted the stratified cluster sampling method for school selection. The full automatic computer optometry (TOPCON RM800) was used to track myopia related parameters for all participants from 2019 to 2020 under the condition of mydriasis (compound topicamide eye drops). Relationship between growth parameters of children and adolescents and the incidence and progression of myopia was analyzed by using Cox regression multiple statistical model. Results: The myopia rates of students from grade 1 to grade 3 in 2019 were 5.4%, 21.5% and 37.3% respectively. After one year, the myopia rates of all school stages increased to 25.3%, 43.3% and 58.1% respectively( χ 2=53.59, 49.63, 32.52, P <0.01). The mean diopter of right eye and left eye after mydriasis were ( 0.30± 1.24/0.39±1.26)D in 2019 and (-0.33±1.54/-0.19±1.55)D in 2020, respectively based on Cox multiple regression results, age ( HR =1.21, 95% CI =1.09-1.34), naked eye vision ( HR =0.08, 95% CI =0.07-0.11), height ( HR =0.98, 95% CI =0.97-0.99) showed a strong correlation with the incidence and progression of myopia( P <0.05). Conclusion Myopia is growing rapidly in the central region of Jiangsu Province. It is suggested that diopter, axial length, naked eye vision, age, height and other indicators should be included in the refractive archives of children and adolescents in the region.

Objective:To investigate the effect of ultrasound-guided transverse abdominal plane block combined with dexmedetomidine on cesarean section.Methods:Eighty pregnant women undergoing elective cesarean section under general anesthesia in Binzhou Central Hospital from October 2017 to October 2019 were included in this study. They were randomly assigned to undergo either cesarean section under general anesthesia followed by patient- controlled intravenous analgesia (control group, n = 40) or ultrasound-guided transverse abdominal plane block combined with intravenous dexmedetomidine administration (observation group, n = 40). Analgesic efficacy and the analgesic effect on puerperas and their newborns were compared between the observation and control groups. Results:At 2, 4 and 12 hours after surgery, the Visual Analogue Scale score in the observation group was (2.1 ± 0.9) points, (2.2 ± 0.7) points, (3.0 ± 0.6) points, respectively, which was significantly lower than (4.4 ± 1.3) points, (4.9 ± 1.2) points, (3.9 ± 0.8) points in the control group, respectively ( t = 8.946, 7.854, 6.246, all P < 0.05). At 2, 4 and 12 hours after surgery, the comfort score in the observation group was (3.4 ± 0.8) points, (3.2 ± 0.7) points, (3.3 ± 0.7) points, respectively, which was significantly higher than (2.1 ± 0.7) points, (2.2 ± 0.9) points and (2.5 ± 0.8) points respectively in the control group ( t = 7.235, 6.130, 5.953, all P < 0.05). After surgery, the number of times the demand button of the anesthesia pump in the observation group was pressed was (8.4 ± 2.9), with the rate of patient satisfaction of 97.50% (39/40), which was significantly higher than that in the control group [13.1 ± 3.7, 77.50% (31/40), t = 7.036, χ2 = 9.347, both P < 0.05). At 1 and 2 days after surgery, the cumulative amount of anesthetics used for patient-controlled intravenous analgesia was (52.1 ± 1.9) mL and (121.7 ± 4.1) mL respectively, which were less than (63.6 ± 2.4) mL and (146.5 ± 5.3) mL in the control group, respectively ( t = 6.240 and 8.842, both P < 0.05). The score of extubation quality in the observation group was significantly lower than that in the control group [(1.3 ± 0.3) points vs. (3.2 ± 0.5) points, t = 6.664, P < 0.05]. There was statistically significant difference in cortisol content between the two groups at 10 minutes after extubation and at the time points of fetus removal, skin incision and intubation (all P < 0.05). In the observation group, the partial pressure of carbon dioxide in the umbilical cord blood was significantly reduced, the partial pressure of oxygen and the oxygenation index in the umbilical cord blood were significantly increased, and Apgar score at 1 minute after birth was significantly increased (all P < 0.05). Conclusion:Ultrasound-guided transverse abdominal plane block combined with dexmedetomidine can enhance the anesthetic effect on cesarean section, prolong analgesic time, reduce the amount of analgesics, improve the operation effect, reduce maternal stress responses, and improve maternal and infant health.

Objective    To explore the application value of synchronous CT-guided percutaneous biopsy followed by radiofrequency ablation in the diagnosis and treatment of lung tumors. Methods    The clinical data of 21 patients with lung tumors were retrospectively analyzed. There were 8 males and 13 females aged 68 (51, 73) years. A total of 24 lesions underwent CT-guided percutaneous biopsy and concurrent radiofrequency ablation. The effectiveness and safety of this protocol were analyzed. Results    All 21 patients successfully completed the procedures. The diameter of 24 lesions was 17.0 (13.3, 19.0) mm. Biopsy specimens met the requirements of pathological diagnosis, and the effectiveness of specimens was 100.0%. The incidence of small amount of pneumothorax/pleural shrinkage after procedures was 19.0% (4/21) and the incidence of tension pneumothorax was 4.7% (1/21). There was no obvious bleeding or other complications. Conclusion    Synchronous CT-guided percutaneous biopsy followed by radiofrequency ablation combines two interventional techniques, which is safe and effective in the diagnosis and treatment of lung tumors, and it is worthy of popularization and application in clinic.