Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective:To analyze the screening results of the Urban Cancer Early Diagnosis and Treatment Project in Qinghai Province from 2019 to 2024.Methods:A summary and statistical analysis were conducted on six years of screening data from the Urban Cancer Early Dia-gnosis and Treatment Program in Qinghai Province,with the high-risk rate,screening rate,and detection rate calculated separately for each type of cancer.Results:From 2019 to 2024,56,882 high-risk individuals were identified.The high-risk rates for lung,colorectal,breast,up-per gastrointestinal,and liver cancer were 22.02%,21.57%,14.23%,13.52%,and 6.10%,respectively.Overall,13,592 individuals com-pleted clinical screening,with detection rates of 0.32%for lung cancer,0.41%for liver cancer,0.08%for precancerous gastric lesions,3.63%for precancerous colorectal lesions,0.08%for esophageal cancer,0.16%for gastric cancer,and 0.14%for colorectal cancer.Conclusions:The implementation of the Urban Cancer Early Diagnosis and Treatment Program in Qinghai Province aids in the early detection of cancer,improves early diagnosis and survival rates,and reduces mortality.Nevertheless,due to low public awareness and limited participation,en-hancements in program management and public outreach are required.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective:To analyze the screening results of the Urban Cancer Early Diagnosis and Treatment Project in Qinghai Province from 2019 to 2024.Methods:A summary and statistical analysis were conducted on six years of screening data from the Urban Cancer Early Dia-gnosis and Treatment Program in Qinghai Province,with the high-risk rate,screening rate,and detection rate calculated separately for each type of cancer.Results:From 2019 to 2024,56,882 high-risk individuals were identified.The high-risk rates for lung,colorectal,breast,up-per gastrointestinal,and liver cancer were 22.02%,21.57%,14.23%,13.52%,and 6.10%,respectively.Overall,13,592 individuals com-pleted clinical screening,with detection rates of 0.32%for lung cancer,0.41%for liver cancer,0.08%for precancerous gastric lesions,3.63%for precancerous colorectal lesions,0.08%for esophageal cancer,0.16%for gastric cancer,and 0.14%for colorectal cancer.Conclusions:The implementation of the Urban Cancer Early Diagnosis and Treatment Program in Qinghai Province aids in the early detection of cancer,improves early diagnosis and survival rates,and reduces mortality.Nevertheless,due to low public awareness and limited participation,en-hancements in program management and public outreach are required.

BACKGROUND:MRI is important for the diagnosis of early knee osteoarthritis.MRI image recognition and intelligent segmentation of knee osteoarthritis using deep learning method is a hot topic in image diagnosis of artificial intelligence. OBJECTIVE:Through deep learning of MRI images of knee osteoarthritis,the segmentation of femur,tibia,patella,cartilage,meniscus,ligaments,muscles and effusion of knee can be automatically divided,and then volume of knee fluid and muscle content were measured. METHODS:100 normal knee joints and 100 knee osteoarthritis patients were selected and randomly divided into training dataset(n=160),validation dataset(n=20),and test dataset(n=20)according to the ratio of 8:1:1.The Coarse-to-Fine sequential training method was used to train the 3D-UNET network deep learning model.A Coarse MRI segmentation model of the knee sagittal plane was trained first,and the rough segmentation results were used as a mask,and then the fine segmentation model was trained.The T1WI and T2WI images of the sagittal surface of the knee joint and the marking files of each structure were input,and DeepLab v3 was used to segment bone,cartilage,ligament,meniscus,muscle,and effusion of knee,and 3D reconstruction was finally displayed and automatic measurement results(muscle content and volume of knee fluid)were displayed to complete the deep learning application program.The MRI data of 26 normal subjects and 38 patients with knee osteoarthritis were screened for validation. RESULTS AND CONCLUSION:(1)The 26 normal subjects were selected,including 13 females and 13 males,with a mean age of(34.88±11.75)years old.The mean muscle content of the knee joint was(1 051 322.94±2 007 249.00)mL,the mean median was 631 165.21 mL,and the mean volume of effusion was(291.85±559.59)mL.The mean median was 0 mL.(2)There were 38 patients with knee osteoarthritis,including 30 females and 8 males.The mean age was(68.53±9.87)years old.The mean muscle content was(782 409.18±331 392.56)mL,the mean median was 689 105.66 mL,and the mean volume of effusion was(1 625.23±5 014.03)mL.The mean median was 178.72 mL.(3)There was no significant difference in muscle content between normal people and knee osteoarthritis patients.The volume of effusion in patients with knee osteoarthritis was higher than that in normal subjects,and the difference was significant(P<0.05).(4)It is indicated that the intelligent segmentation of MRI images by deep learning can discard the defects of manual segmentation in the past.The more accuracy evaluation of knee osteoarthritis was necessary,and the image segmentation was processed more precisely in the future to improve the accuracy of the results.

Plasmids are the most commonly used gene carriers in the field of gene synthesis and sequencing. However, the main problems faced by traditional plasmid DNA extraction technology are low extraction throughput and high production cost, so they cannot meet the growing demand. In this study, a double-magnetic-bead method (DMBM) for plasmid extraction was developed based on the principle of plasmid extraction. The effects of the input of magnetic beads, the size of plasmid DNA fragments, and the volume of bacterial on plasmid DNA extraction were explored. In addition, the quality, throughput, and cost of plasmid DNA extraction were also compared between this technique and the commercial plasmid DNA extraction kits. The results showed that the DMBM can meet the needs of extracting plasmid DNA with different cell densities and fragment lengths. Moreover, the sensitivity and quality of plasmid extraction by the DMBM method were both superior to those of the centrifugal adsorption column method. In addition, this technique could be applied on a 96-channel automated nucleic acid extractor, resulting in higher purity of the extracted plasmid DNA, 80% reduction in extraction time, and 57.1% reduction in cost. It also reduces manual operations, achieving high-throughput and low-cost plasmid DNA extraction, thus may facilitate gene synthesis and sequencing.
Plasmids/genetics* ; DNA/genetics* ; Nucleic Acids ; Genetic Techniques ; Magnetic Phenomena

Objective:To investigate the role of chemokine receptor CX3CR1 in chronic skin inflammation and its regulatory mechanism.Methods:Wild type (WT) C57BL/6 mice and Cx3 cr1 GFP/GFP mice were induced by DNFB to establish acute and chronic allergic contact dermatitis (ACD) model. Ear inflammation and swelling were observed with hematoxylin-eosin (HE) staining. Flow cytometry (FCM) was used to detect the changes in classical Langerhans cell (LC) and monocyte-derived LC (Mo-LC), as well as the expression of major histocompatibility complex Ⅱ (MHCⅡ), inducible nitric oxide synthase (iNOS) and TNF-α. Changes in epidermal LC in UV irradiation-induced dermatitis models were also analyzed. In human chronic skin inflammation, CX3CL1 expression was detected using immunohistochemistry, RT-PCR and Western blot and CD1a, CD14 and CD207 expression was observed with immunofluorescence staining. Results:In the chronic ACD model, Cx3 cr1 GFP/GFP mice showed significantly alleviated ear inflammatory and swelling as compared with WT mice, but no significant difference was found in the acute ACD model. The percentages of Mo-LC were decreased in the chronic ACD model and after three weeks of UV irradiation. Moreover, MHCⅡ, TNF-α and iNOS expressed by Mo-LC were significantly upregulated as compared with those by classical LC. CX3CL1 expression was significantly upregulated and the numbers of CD14 + monocytes and CD1a + langerin - Mo-LC were dramatically increased in human chronic skin inflammation. Conclusions:CX3CR1 might maintain inflammatory response by regulating local remodeling of Mo-LC in chronic skin inflammation.

Objective:To investigate the optimal monoenergetic level of virtual monoenergetic images (VMI) in transplanted renal artery on a dual-layer spectral detector CT.Methods:A retrospective study was performed on 16 renal transplant patients who underwent transplanted renal angiography on a dual-layer spectral detector CT in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2020 to April 2021. Conventional 120 kVp polyenergetic images (PI) were reconstructed, and virtual monoenergetic images (VMIs) in range of 40-200 keV with interval of 10 keV were reconstructed, too. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of 120 kVp PI and VMIs were measured. Meanwhile, the subjective scores of the display of transplanted renal artery were performed on volume rendering images of 120 kVp PI and VMIs. Spearman correlation analysis was used to explore the correlation between energy levels and SNR or CNR. Rank sum tests were performed to compare the parameters of image quality between the VMI which had the highest SNR and CNR, and the other VMIs, or 120 kVp PI.Results:Among the VMIs, SNR or CNR was negatively correlated with energy levels ( r =-0.86 and -0.88, all P<0.001). The SNR [22.80(18.57, 34.16)] and CNR [35.38(25.97, 39.01)] of 40 keV VMI were the highest, and significantly higher than that of 120 kVp PI and 50-200 keV VMIs, all the differences were statistically significant (all P<0.05). The subjective scores of 40 keV VMI and 120 kVp PI were 5 (5, 5) and 4 (3, 5), respectively. The score of 40 keV VMI was significantly higher than that of 120 kVp PI ( Z=-2.60, P=0.009). There were no significant differences in subjective scores between 40 keV VMI and 50-70 keV VMIs ( Z=-1.00, -1.41, -1.73, P=0.317, 0.157, 0.083), but the subjective score of 40 keV VMI was higher than that of 80-200 keV VMIs and the differences were statistically significant (all P<0.05). Conclusions:As for the images of transplanted renal angiography on a dual-layer spectral detector CT, the image quality of 40 keV VMI was best, thus 40 keV was the optimal monoenergetic level.

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in

Objective:To investigate the role of Sestrin2 overexpression in regulating mitochondrial fission and its mechanism in human neuroblastoma SH-SY5Y cell model of glucose and oxygen deprivation/recovery (OGD/R). Methods:(1) SH-SY5Y cells were divided into normal control group, OGD/R group, Vector group, and Sestrin2 overexpression group; Sestrin2 overexpression or empty vector stable cell lines in the Sestrin2 overexpression group and Vector group were constructed by lentivirus infection; cells in the later 3 groups were subjected to oxygen-glucose deprivation (OGD) for 4 h followed by restoration of O 2 supply for 18 h. The cell survival rate was detected by cell counting kit (CCK)-8 assay. The protein levels of Sestrin2, dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Kelch-like ECH-related protein 1 (Keap1) in the cytoplasm and nuclear factor E2-related factor (Nrf2) in the nucleus were detected by Western blotting. The mitochondria ultrastructure was observed by transmission electron microscope. The Nrf2 nuclear translocation was detected by immunofluorescence staining. (2) Cell lines with Sestrin2 overexpression were divided into Sestrin2 overexpression group, Brusatol+ Sestrin2 overexpression group, and DMSO+ Sestrin2 overexpression group. Cells in the Brusatol+ Sestrin2 overexpression group were pretreated with normal medium containing Brusatol (Keap1/Nrf2 pathway inhibitor, final concentration: 100 nmol/L) for 4 h before OGD/R; cells in the DMSO+ Sestrin2 group were pretreated with normal medium containing DMSO (final volume fraction: 0.1%) for 4 h before OGD/R. Cells in these groups were then subjected to OGD for 4 h followed by restoration of O 2 supply for 18 h. The protein levels of Drp1, Fis1, Keap1 in the cytoplasm, and Nrf2 in the nucleus were measured by Western blotting. Results:(1) As compared with those in the OGD/R group, cells in the Sestrin2 overexpression group had significantly increased survival rate (61.33%±1.15% vs. 81.00%±3.00%), significantly up-regulated Bcl-2/Bax ratio (0.467±0.006 vs. 0.880±0.010), significantly decreased Drp1, Fis1 and cytoplasmic Keap1 protein levels (1.089±0.033 vs. 0.865±0.014; 0.829±0.009 vs. 0.350±0.007; 0.967±0.017 vs. 0.881±0.024), and significantly up-regulated nuclear Nrf2 protein level (0.627±0.025 vs. 0.957±0.015, P<0.05). The mitochondrial structure in the Sestrin2 overexpression group under electron microscope was more complete than that in the OGD/R group, and obvious nuclear translocation of Nrf2 was noted. (2) As compared with the Sestrin2 overexpression group, Brusatol+ Sestrin2 overexpression group had significantly decreased nuclear Nrf2 protein level (0.920±0.013 vs. 0.627±0.035), and statistically increased Drp1 and Fis1 protein levels (0.994±0.020 vs. 1.084±0.005; 0.728±0.010 vs. 0.906±0.022, P<0.05). Conclusion:Sestrin2 overexpression could suppress mitochondrial fission, reduce cell apoptosis, and attenuate OGD/R injury of SH-SY5Y cells by activating Keap1/Nrf2 pathway via down-regulating cytoplasmic Keap1 protein level and promoting Nrf2 nuclear translocation.