In order to investigate the effects of vector-based hairpin small interference RNA (shRNA) on the reversal of multi-drug resistance (mdr) of A2780/Taxol cells, a novel vector pEGFP-H1/mdr1 containing mdr1-shRNA targeting at position 2943-2963 of mdr1 was designed and synthesized. Subsequently, A2780/Taxol cells were transfected with pEGFP-H1/mdr1, and the expression of mdr1 mRNA and P-gp was detected by using RT-PCR and Western blot respectively. MTT was used to measure the 50% inhibition concentration (IC(50)) of Taxol to A2780/Taxol cells. The results showed that at the 24th and 48th h after transfection, the expression of mdr1 mRNA was decreased to (52.1+/-1.0)% and (0.01+/-1.7)%, and that of P-gp decreased to (88.3+/-2.1)% and 0%, respectively. At the 48th h after transfection, the relative reversal rate of A2780/Taxol cells to Taxol was 69.54%. In vivo, the nude mice xenografts were injected with pEGFP-H1/mdr1, and then administrated Taxol. The tumor volume in pEGFP-H1/mdr1-transfected group was significantly reduced as compared with that in blank control group or pEGFP-H1-transfected group (807.20+/-103.16 vs 1563.78+/-210.54 or 1480.78+/-241.24 mm(3), both P<0.01). These results suggested that transfection of pEGFP-H1/mdr1 could efficiently down-regulate the expression of mdr1 mRNA and P-gp in A2780/Taxol cells, and effectively restore the sensitivity of A2780/Taxol cells to Taxol both in vitro and in vivo.

In order to investigate the effects of vector-based hairpin small interference RNA (shRNA) on the reversal of multi-drug resistance (mdr) of A2780/Taxol cells, a novel vector pEGFP-H1/mdr1 containing mdr1-shRNA targeting at position 2943-2963 of mdr1 was designed and synthesized.Subsequently, A2780/Taxol cells were transfected with pEGFP-H1/mdrl, and the expression of mdr1 mRNA and P-gp was detected by using RT-PCR and Western blot respectively. MTT was used to measure the 50% inhibition concentration (1C50) of Taxol to A2780/Taxol cells. The results showed that at the 24th and 48th h after transfection, the expression of mdr1 mRNA was decreased to (52.1±1.0)% and (0.01+1.7)%, and that of P-gp decreased to (88.3±2.1)% and 0%, respectively. At the 48th h after transfection, the relative reversal rate of A2780/Taxol cells to Taxol was 69.54%. In vivo, the nude mice xenografts were injected with pEGFP-H1/mdrl, and then administrated Taxol.The tumor volume in pEGFP-H1/mdr1-transfected group was significantly reduced as compared with that in blank control group or pEGFP-H1-transfected group (807.20±103.16 vs 1563.78±210.54 or 1480.78±241.24 mm3, both P<0.01). These results suggested that transfection of pEGFP-H1/mdr1 could efficiently down-regulate the expression of mdr1 mRNA and P-gp in A2780/Taxol cells, and effectively restore the sensitivity of A2780/Taxol cells to Taxol both in vitro and in vivo.

MicroRNAs (miRNAs) that exert function by posttranscriptional suppression have recently brought insight in our understanding of the role of non-protein-coding RNAs in carcinogenesis and metastasis. In this study, we described the function and molecular mechanism of miR-139-5p in colorectal cancer (CRC) and its potential clinical application in CRC. We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues (NCTs), and decreased miR-139-5p was associated with poor prognosis. Functional analyses demonstrated that ectopic expression of miR-139-5p suppressed CRC cell migration and invasion in vitro and metastasis in vivo. Mechanistic investigations revealed that miR-139-5p suppress CRC cell invasion and metastasis by targeting AMFR and NOTCH1. Knockdown of the two genes phenocopied the inhibitory effect of miR-139-5p on CRC metastasis. Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression. Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients. Together, our data indicate that miR-139-5p is a potential tumor suppressor and prognostic factor for CRC, and targeting miR-139-5p may repress the metastasis of CRC and improve survival.
Animals ; Base Sequence ; Cell Line, Tumor ; Cell Movement ; genetics ; Colorectal Neoplasms ; genetics ; pathology ; therapy ; Down-Regulation ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; HCT116 Cells ; HEK293 Cells ; Humans ; Male ; Mice, Inbred BALB C ; Mice, Nude ; MicroRNAs ; genetics ; Middle Aged ; Neoplasm Invasiveness ; RNA Interference ; Receptor, Notch1 ; genetics ; metabolism ; Receptors, Autocrine Motility Factor ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology, Nucleic Acid ; Survival Analysis ; Xenograft Model Antitumor Assays

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Magnetic resonance (MR) imaging is an important tool for prostate cancer diagnosis, and accurate segmentation of MR prostate regions by computer-aided diagnostic techniques is important for the diagnosis of prostate cancer. In this paper, we propose an improved end-to-end three-dimensional image segmentation network using a deep learning approach to the traditional V-Net network (V-Net) network in order to provide more accurate image segmentation results. Firstly, we fused the soft attention mechanism into the traditional V-Net's jump connection, and combined short jump connection and small convolutional kernel to further improve the network segmentation accuracy. Then the prostate region was segmented using the Prostate MR Image Segmentation 2012 (PROMISE 12) challenge dataset, and the model was evaluated using the dice similarity coefficient (DSC) and Hausdorff distance (HD). The DSC and HD values of the segmented model could reach 0.903 and 3.912 mm, respectively. The experimental results show that the algorithm in this paper can provide more accurate three-dimensional segmentation results, which can accurately and efficiently segment prostate MR images and provide a reliable basis for clinical diagnosis and treatment.
Male ; Humans ; Prostate/diagnostic imaging* ; Image Processing, Computer-Assisted/methods* ; Magnetic Resonance Imaging/methods* ; Imaging, Three-Dimensional/methods* ; Prostatic Neoplasms/diagnostic imaging*

MicroRNAs (miRNAs) are a type of small non-coding RNAs that are often play important roles in carcinogenesis, but the carcinogenic mechanism of miRNAs is still unclear. This study will investigate the function and the mechanism of miR-638 in carcinoma (GC). The expression of miR-638 in GC and the DNA copy number of miR-638 were detected by real-time PCR. The effect of miR-638 on cell proliferation was measured by counting kit-8 assay. Different assays, including bioinformatics algorithms (TargetScan and miRanda), luciferase report assay and Western blotting, were used to identify the target gene of miR-638 in GC. The expression of miR-638 target gene in clinical CRC tissues was also validated by immunohistochemical assay. From this research, we found that miR-638 was downregulated in GC tissues compared with corresponding noncancerous tissues (NCTs), and the DNA copy number of miR-638 was lower in GC than NCTs, which may induce the corresponding downregulation of miR-638 in GC. Ectopic expression of miR-638 inhibited GC cell growth in vitro. Subsequently, we identified that PLD1 is the target gene of miR-638 in GC, and silencing PLD1 expression phenocopied the inhibitory effect of miR-638 on GC cell proliferation. Furthermore, we observed that PLD1 was overexpressed in GC tissues, and high expression of PLD1 in GC predicted poor overall survival. In summary, we revealed that miR-638 functions as a tumor suppressor in GC through inhibiting PLD1.
3' Untranslated Regions ; genetics ; Apoptosis ; genetics ; Base Sequence ; Cell Line, Tumor ; Cell Proliferation ; genetics ; Down-Regulation ; genetics ; Humans ; MicroRNAs ; genetics ; Phospholipase D ; genetics ; Prognosis ; Stomach Neoplasms ; diagnosis ; enzymology ; genetics ; pathology

SIRT7, a sirtuin family member implicated in aging and disease, is a regulator of metabolism and stress responses. It remains elusive how human somatic stem cell populations might be impacted by SIRT7. Here, we found that SIRT7 expression declines during human mesenchymal stem cell (hMSC) aging and that SIRT7 deficiency accelerates senescence. Mechanistically, SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins, thus maintaining the repressive state of heterochromatin at nuclear periphery. Accordingly, deficiency of SIRT7 results in loss of heterochromatin, de-repression of the LINE1 retrotransposon (LINE1), and activation of innate immune signaling via the cGAS-STING pathway. These aging-associated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor. Together, these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.

OBJECTIVE To evaluate the cost -effectiveness of tislelizumab in the second -line treatment of advanced or metastatic esophageal squamous cell carcinoma （ESCC）in China .METHODS A three -state Markov model was constructed to assess the cost -effectiveness of tislelizumab versus chemotherapy in the second -line treatment of advanced or metastatic ESCC and programmed death receptor 1（PD-L1）positive patients . The cycle length of the model was 1 month，and the time horizon of the model was set as 10 years. The discount rate of cost and utility was 5%. One-way sensitivity analysis ，probability sensitivity analysis and scenario analysis were used to verify the robustness of the base -case analysis results . RESULTS The results of the base-case analysis showed that compared with chemotherapy ，the incremental cost -effectiveness ratio （ICER）of tislelizumab in the second-line treatment of advanced or metastatic ESCC and PD -L1-positive patients were 26 864.01 yuan/QALY and 37 510.07 yuan/QALY，respectively，which was much lower than 1 time per capita gross domestic product （GDP）in 2021（80 976 yuan）. Results of scenario analysis showed that the ICER was less than 1 times per capita GDP ，regardless of the chemotherapy regimens（paclitaxel，docetaxel or irinotecan ）used. With the extension of the simulation time limit ，the ICER of tirelizumab regimen gradually decreased ，and the reduction rate gradually E-mail：lishunping@sdu.edu.cn decreased，but they were all less than 1 time China ’s per capita GDP in 2021. The results of the one -way sensitivity analysis showed that the 3 parameters with the most significant impact on the ICER were progression -free survival of tislelizumab group ，price of tislelizumab ，and the proportion of patients receiving follow-up treatment in the tislelizumab group . The results of the probability sensitivity analysis showed that the probability of tislelizumab with cost -effectiveness in the treatment of advanced or metastatic ESCC patients and PD -L1-positive patients were 99.09% and 99.94%，respectively，when using 3 times per capita GDP as the willingness -to-pay threshold . CONCLUSIONS Tislelizumab has economic advantages over chemotherapy alone in the second -line treatment of advanced or metastatic ESCC patients.

OBJECTIVE To review the current research progress on pharmacoeconomics evaluation related to spinal muscular atrophy （SMA）， in order to provide valuable insights for clinical treatment， screening and medical insurance payment decision- making. METHODS A computerized search was conducted across multiple databases including PubMed， Web of Science， Embase， Scopus， Cochrane Library， EBSCOhost， CNKI， VIP， CBM and Wanfang database as well as other important health technology assessment （HTA） websites， such as National Institute for Health and Care Research，International Society of Technology Assessment in Health Care， Agency for Healthcare Research and Quality， etc. The pharmacoeconomics evaluation studies related to SMA were collected from the inception to December 31st， 2023. The literature/reports were rigorously screened based on predefined inclusion and exclusion criteria by two researchers， and the essential information from the included literature/ reports was extracted using Excel 2019. The quality of the included literature/reports was evaluated by Consolidated Health Economic Evaluation Reporting Standards 2022. RESULTS Finally， 9 articles and 15 HTA reports were included， with overall good quality of literature， but poor quality of HTA reports. There were a total of 24 studies on the pharmacoeconomics evaluation of SMA， including treatment options such as nusinersen sodium， sovaprevir， risperidone， and best supportive therapy.The review results showed that nusinersen sodium was not cost-effective in the treatment of SMA； there was no consensus on the economic viability of treatment options such as risperidone and sovaprevir； newborn/prenatal screening combined withmedication therapy was cost-effective. CONCLUSIONS newborn/prenatal screening combined with SMA medication therapy demonstrates economic advantages. It is suggested to further investigate the cost-effectiveness of new SMA drugs and SMA screening in China， taking localization parameters and medical insurance prices into account， and gradually incorporate SMA screening into the scope of neonatal genetic disease detection， in order to alleviate the financial burden of patients’ families and healthcare systems.