Objective To compare the performance of 7 Chinese-developed GenAI models (DeepSeek, Wenxin Yiyan, Tongyi, Doubao, Kimi, Hunyuan, and iFLYTEK Spark) in responding to common diseases of the pediatric genitourinary system and to explore their potential applications.Methods A total of 80 questions covering basic disease information, diagnosis, treatment, and prognosis related to “hypospadias, hydronephrosis, and cryptorchidism” were developed as prompts.The models were tested under 3 modes:“quick thinking, ”“deep thinking, ” and “deep thinking + internet access.” The results were evaluated in a blinded review by two pediatric urologists.The responses were graded into 4 levels—A, B, C, and D—based on accuracy, completeness, and relevance.The proportions of responses rated as A and A+B were statistically analyzed and compared across the different models/modes.Results The “deep thinking” mode of DeepSeek demonstrated the best performance, with 88% of responses rated as A and 96% rated as A+B.DeepSeek (deep thinking + internet access), Doubao (quick thinking), Hunyuan (deep thinking), and Doubao (deep thinking + internet access) followed closely, also showing excellent response capabilities.Among the top 5 models/modes, significant differences were observed in the proportion of Alevel responses (P＜0.05), while differences in the proportion of A+B-level responses were not statistically significant (P＞0.05).Conclusion Certain Chinese-developed GenAI models, represented by DeepSeek (deep thinking), demonstrate significant application potential.However, they still cannot consistently provide recommendations rated at the A+B level (recommended grade or higher) with 100% accuracy.In clinical practice, both doctors and patients should view GenAI as an auxiliary tool for education and information acquisition rather than as a final decision-making authority.All information must be reviewed and confirmed by professional physicians.

Objective To discuss the improvement for the verification of inter-day precision of PS activity assay and the verification protocol for limits of quantitative of FⅧ:C and FⅨ:C assay,aiming at the problems in the performance verification of anticoagulant protein S(PS),coagulation factor Ⅷ activity(F Ⅷ:C)and coagulation factor Ⅸ activity(F Ⅸ:C)assay.Methods SYSMEX CN-6000 and supporting reagents were used,and low-and high-value quality control(QCs)were used as the study samples.Following the American Clinical and Laboratory Standards Institute(CLSI)document EP15-A3,an inter-day precision verification study of the PS activity assay was performed with three reagent preparation methods designed(specification-required method,instrument's manual method and improved method).The specification-required method was carried out completely according to the specification,and the instrument manual method involved allowing the required reagents to stand in the device for 30 minutes based on the specification-required method,and the improved method mixed and dispensed the reagents needed to be based on the specification-required method.To study the bottle variation of the same batch of reagents for the same sample,the acceptable range of external quality assessment(EQA)of the National Center for Clinical Laboratories(NCCL)was used as the evaluation standard.Following the CLSI EP25 document,the PS activity assay reagent onboard stability verification was performed with the specification-required method and the improved method.Following the CLSI EP17-A2 document,WS/T 514-2017"Establishment and Verification of Detection Capability for Clinical Laboratory Measurement Procedures"and the International Committee for Standardization in Hematology(ICSH)guidelines,the LoQ for FVIII:C and FIX:C assays was verified.The verification results were passed if the requirements of the specification were met.Results The verification result of inter-day precision(CVWL:12.9%～21.6%)of PS activity assay according to the specification method and the instrumental manual method exceeded the requirements of the specification(<10%CVWL at high levels,<20%CVWL at low levels).The results of inter-day precision verification with the improved method(CVWL:2.9%and 4.5%)were consistent with the requirements of the specification.The bottle variation exceeded the acceptable range of EQA.The improved method corrected the reagent on-board stability verification results of reagents(relative deviations of-4.24%～9.97%)by the specifications(high levels<10%,low levels<20%).The LoQ verification results for FⅧ:C and FⅨ:C assay were by the product specifications(FⅧ:C:0.75%～1.46%and 0.74%～1.40%;FⅨ:C:0.71%～1.27%and 0.70%～1.32%).Conclusion An improved method to improve the inter-day precision of PS activity detection is provided,and LoQ verification protocol for F Ⅷ:C and FⅨ:C assay is provided for clinical laboratory reference.

Objective To discuss the improvement for the verification of inter-day precision of PS activity assay and the verification protocol for limits of quantitative of FⅧ:C and FⅨ:C assay,aiming at the problems in the performance verification of anticoagulant protein S(PS),coagulation factor Ⅷ activity(F Ⅷ:C)and coagulation factor Ⅸ activity(F Ⅸ:C)assay.Methods SYSMEX CN-6000 and supporting reagents were used,and low-and high-value quality control(QCs)were used as the study samples.Following the American Clinical and Laboratory Standards Institute(CLSI)document EP15-A3,an inter-day precision verification study of the PS activity assay was performed with three reagent preparation methods designed(specification-required method,instrument's manual method and improved method).The specification-required method was carried out completely according to the specification,and the instrument manual method involved allowing the required reagents to stand in the device for 30 minutes based on the specification-required method,and the improved method mixed and dispensed the reagents needed to be based on the specification-required method.To study the bottle variation of the same batch of reagents for the same sample,the acceptable range of external quality assessment(EQA)of the National Center for Clinical Laboratories(NCCL)was used as the evaluation standard.Following the CLSI EP25 document,the PS activity assay reagent onboard stability verification was performed with the specification-required method and the improved method.Following the CLSI EP17-A2 document,WS/T 514-2017"Establishment and Verification of Detection Capability for Clinical Laboratory Measurement Procedures"and the International Committee for Standardization in Hematology(ICSH)guidelines,the LoQ for FVIII:C and FIX:C assays was verified.The verification results were passed if the requirements of the specification were met.Results The verification result of inter-day precision(CVWL:12.9%～21.6%)of PS activity assay according to the specification method and the instrumental manual method exceeded the requirements of the specification(<10%CVWL at high levels,<20%CVWL at low levels).The results of inter-day precision verification with the improved method(CVWL:2.9%and 4.5%)were consistent with the requirements of the specification.The bottle variation exceeded the acceptable range of EQA.The improved method corrected the reagent on-board stability verification results of reagents(relative deviations of-4.24%～9.97%)by the specifications(high levels<10%,low levels<20%).The LoQ verification results for FⅧ:C and FⅨ:C assay were by the product specifications(FⅧ:C:0.75%～1.46%and 0.74%～1.40%;FⅨ:C:0.71%～1.27%and 0.70%～1.32%).Conclusion An improved method to improve the inter-day precision of PS activity detection is provided,and LoQ verification protocol for F Ⅷ:C and FⅨ:C assay is provided for clinical laboratory reference.

Objective:To analyze the operational efficiency and Total Factor Productivity (TFP) of township health centers in Ningxia from 2013 to 2022,in order to provide decision-making basis for optimize the resource allocation of township health centers in Ningxia. Methods:The BCC model of Data Envelopment Analysis (DEA) and Malmquist productivity index were used to analyze the operation efficiency and TFP of township health centers of Ningxia. Results:(1) From 2013 to 2022,the personnel input in Ningxia township health centers increased by 45.80％,the number of outpatient visits had no significant increase,and the number of inpatient visits decreased by 45.40％. (2) The average comprehensive technical efficiency of resource allocation was 0.658,the average of pure technical efficiency and scale efficiency were 0.747 and 0.880. (3) The average value of TFP index was greater than 1 in 7 counties,and less than 1 in the other 15 counties. Conclusion:The efficiency of township health centers in Ningxia was low. It is of great significance to improve the resource allocation and management ability of township health centers and strengthen the policy support for improving the operation efficiency of township health centers.

Objective:To analyze the operational efficiency and Total Factor Productivity (TFP) of township health centers in Ningxia from 2013 to 2022,in order to provide decision-making basis for optimize the resource allocation of township health centers in Ningxia. Methods:The BCC model of Data Envelopment Analysis (DEA) and Malmquist productivity index were used to analyze the operation efficiency and TFP of township health centers of Ningxia. Results:(1) From 2013 to 2022,the personnel input in Ningxia township health centers increased by 45.80％,the number of outpatient visits had no significant increase,and the number of inpatient visits decreased by 45.40％. (2) The average comprehensive technical efficiency of resource allocation was 0.658,the average of pure technical efficiency and scale efficiency were 0.747 and 0.880. (3) The average value of TFP index was greater than 1 in 7 counties,and less than 1 in the other 15 counties. Conclusion:The efficiency of township health centers in Ningxia was low. It is of great significance to improve the resource allocation and management ability of township health centers and strengthen the policy support for improving the operation efficiency of township health centers.

Objective: To compare the differences and similarities among the system of quality of life instruments for cancer patients (QLICP) V1.0, the quality of life questionnaire (QLQ) from European Organization for Research and Treatment of Cancer (EORTC) and Functional Assessment of Cancer Therapy (FACT) from Center on Outcomes, Research and Education (CORE) of America. Methods: Based on literatures and our measuring data from patients at hospitals, the constructs, characteristics and psychometrics of the systems above were analyzed and compared. Internal consistency reliability was assessed using Cronbach α coefficient for each domain, and test-retest reliability through calculating the Pearson correlation coefficient r between the first and second assessments as well as intra-class correlation (ICC). Construct validity was evaluated by Pearson correlation coefficient r (item-domains correlations) and factor analysis. The criterion-related validity was evaluated by correlating corresponding domains of two instruments. Responsiveness was assessed through comparing the mean difference between the pre-treatment and post-treatment with standardized response mean (SRM). Results: The instruments of three systems were of different outstanding characteristics with all psychometrics meeting requirements. Measurements for 12 types of cancers showed that the internal consistency reliability Cronbach α coefficient for the overall scale of QLICP (V1.0) was 0.67-0.92, and for FACT was 0.79-0.98. The test-retest reliability (r or ICC) for the overall scale of QLICP (V1.0) was 0.61-0.99, and for FACT was 0.60-0.98. The SRM for the overall scale of QLICP (V1.0) was 0.25-1.28, and for FACT was 0.11-0.83. However, the QLICP was of better construct (clear hierarchical structure with items→facets→domains→overall) and Chinese culture. Conclusion The instruments of three systems can be used as the instruments to assess quality of life for patients with cancer with selections basing on different settings.

Objective To investigate the inhibitory effect of 188 Re-labeled BaGdF5-poly ( ethylene glycol) ( PEG) nanoparticles ( NPs) on hepatoma cells, and explore the application of the radiolabeled NPs for SPECT imaging. Methods BaGdF5-PEG NPs were synthesized by hydrothermal method, and were fur-ther radiolabeled with 188Re using diethylene triamine pentaacetic acid (DTPA) as a coupling agent. The human hepatoma cells SMCC 7721 were treated with different concentrations of BaGdF5-PEG NPs, 188 ReO-4 or 188Re-DTPA-BaGdF5 NPs (14.8, 74.0, 370.0×104 Bq/ml) for 24 h, and then the cell proliferation rates were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. 188ReO-4 and 188 Re-DTPA-BaGdF5 NPs were administrated into normal rabbits via the ear vein, respectively. For the former, static SPECT/CT imaging were performed at 30, 60 min post-injection, and for the latter, dynamic SPECT images were captured within 10 min, and static SPECT/CT images at 30, 60, 120 min post-injec-tion. The rabbit VX2 tumor model was established, and a microcatheter was inserted into hepatic artery via the rabbit femoral artery, and then the mixture of 188 Re-DTPA-BaGdF5 NPs and lipiodol was injected into the tumor region. SPECT/CT imaging for VX2 tumor was performed at 30 min later. Data were analyzed by two-sample t test. Results The BaGdF5-PEG NPs were nearly square and the particle size was about 10 nm. The labeling yield of 188 Re-DTPA-BaGdF5 was 94.1％ at the optimum conditions. Moreover, it showed high stability in vitro and in vivo. In vitro, BaGdF5-PEG NPs did not exhibit obvious cytotoxicity even at a high concentration. Both 188 ReO-4 and 188 Re-DTPA-BaGdF5 could inhibit the proliferation of SMCC 7721 cells, but 188 Re-DTPA-BaGdF5 showed a significantly stronger inhibitory effect at the doses of 74.0 and 370.0×104 Bq/ml ( t values:4.21,4.09, both P<0.01) . In vivo, 188 ReO-4 was absorbed by maxillary glands and was quickly elimi-nated from blood via the kidneys. The 188 Re-DTPA-BaGdF5 NPs mainly accumulated in the liver and spleen. In addition, retention and accumulation of 188 Re-DTPA-BaGdF5 NPs in the liver tumor could be achieved by using transarterial intervention technique for drug delivery. Conclusion 188Re-DTPA-BaGdF5 NPs have cer-tain killing effects on hepatoma cells in vitro, and with the help of transarterial intervention technique, the NPs can be aggregated within liver tumor, where they not only can be used for SPECT imaging, but also have potential therapeutic effects.

As a dioxygenase, Ten-Eleven Translocation 2 (TET2) catalyzes subsequent steps of 5-methylcytosine (5mC) oxidation. TET2 plays a critical role in the self-renewal, proliferation, and differentiation of hematopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Deletion of Tet2 impairs the differentiation of osteoclast precursor cells (macrophages) and their maturation into bone-resorbing osteoclasts in vitro. Furthermore, Tet2 mice exhibit mild osteopetrosis, accompanied by decreased number of osteoclasts in vivo. Tet2 loss in macrophages results in the altered expression of a set of genes implicated in osteoclast differentiation, such as Cebpa, Mafb, and Nfkbiz. Tet2 deletion also leads to a genome-wide alteration in the level of 5-hydroxymethylcytosine (5hmC) and altered expression of a specific subset of macrophage genes associated with osteoclast differentiation. Furthermore, Tet2 interacts with Runx1 and negatively modulates its transcriptional activity. Our studies demonstrate a novel molecular mechanism controlling osteoclast differentiation and function by Tet2, that is, through interactions with Runx1 and the maintenance of genomic 5hmC. Targeting Tet2 and its pathway could be a potential therapeutic strategy for the prevention and treatment of abnormal bone mass caused by the deregulation of osteoclast activities.
5-Methylcytosine ; analogs & derivatives ; chemistry ; metabolism ; Animals ; Cell Differentiation ; Cells, Cultured ; Core Binding Factor Alpha 2 Subunit ; genetics ; metabolism ; DNA-Binding Proteins ; physiology ; Genome ; Genomics ; Mice ; Mice, Knockout ; Osteoclasts ; cytology ; metabolism ; Proto-Oncogene Proteins ; physiology

BACKGROUND:Our previous studies have found that polygonatum sibiricum polysaccharide (PSP) promotes osteogenic differentiation of bone marrow mesenchymal stem cel s (BMSCs) by Wnt/β-catenin signaling pathway, but the molecular mechanism is unclear.OBJECTIVE:To investigate the effect of PSP promoting the osteogenic differentiation via Wnt signaling pathways in BMSCs after LRP5 silencing. METHODS:LRP5 interference vectors were constructed and then transfected into C57BL/6 mouse BMSCs cultured in vitro. The transfection efficiency of cel s was calculated under fluorescence inverted microscope and the expression of LRP5 protein was detected by western blot assay. The osteogenic potential of BMSCs after LRP5-siRNA transfection was analyzed by alkaline phosphatase staining, alizarin red staining and western blot assay. Effect of PSP on the osteogenic differentiation of LIRP5-silenced mouse BMSCs was detected by real-time PCR and dual luciferase assay. RESULTS AND CONCLUSION:Compared with the control group, the mineralization ability, the mRNA expressions of Runx2 and Osterix, and the protein expression of LRP5 were significantly decreased in the LRP5-siRNA group (P<0.05). PSP could promote LRP5-siRNA transfected mouse BMSCs differentiating into osteoblasts and significantly upregulated the expressions ofβ-catenin and Osterixin, and also induced the high expression of luciferase reporter gene (TOPFlash) containing wild type TCF binding sites (P<0.05). To conclude, LRP5 plays an important role in the process of mouse BMSCs differentiating into osteoblasts. PSP can promote the osteogenic differentiation of mouse BMSCs by activating the Wnt/β-catenin signaling pathway independent on LRP5.

Objective:To investigate the effect of long-chain non-coding CDKN2B targeting miR-19 on the biological behavior of chronic myeloid leukemia cells and its mechanism.Methods: The expression of CDKN2B in different leukemia cells were detected by qPCR.Double luciferase reporter gene was used to detect the interaction between CDKN2B and miR-19.MTT proliferation assay and flow cytometry were used to detect the effect of CDKN2B on the proliferation and apoptosis of HL-60 cells.The changes of migration ability of leukemia HL-60 cells after overexpress of CDKN2B were detected by scratch test.The changes of invasion ability of leukemia HL-60 cells after silencing CDKN2B were detected by Transwell invasion assay.Scaling healing experiment and Transwell invasion assay were used to detect the effect of miR-19 on the migration and invasion of leukemia cells after silencing CDKN2B.The morphological changes of cytoskeleton microfilament microtubules after silencing CDKN2B were detected by phalloidin staining.Western blot was used to detect the expression of PI3K/AKT signaling pathway after silencing CDKN2B.Results: The expression level of CDKN2B was the lowest in leukemia cell HL-60.CDKN2B binds specifically to the 3′UTR of miR-19;overexpression of CDKN2B could inhibit the proliferation and enhance the apoptosis of leukemia HL-60 cells.Overexpression of CDKN2B can inhibit the invasion and migration of leukemia HL-60 cells.After overexpressed of CDKN2B,the cytoskeleton showed decreased pseudopodia and decreased exercise capacity.The expression of actin was down-regulated.The expression of PI3K/AKT pathway protein was down-regulated after overexpressed of CDKN2B.Conclusion: CDKN2B can target the regulation of miR-19 to regulate the biological behavior of leukemia cells.