DNA methylation,a crucial biochemical process within the human body,fundamentally alters gene expression without modifying the DNA sequence,resulting in stable changes.The changes in DNA methylation are closely related to numerous biological processes including cellular proliferation and differentiation,embryonic development,and the occurrence of immune diseases and tumor.Specifically,abnormal DNA methylation plays a crucial role in the formation,progression,and prognosis of chronic myeloid leukemia(CML).Moreover,DNA methylation offers substantial potential for diagnosing and treating CML.Accordingly,understanding the precise mechanism of DNA methylation,particularly abnormal changes in the methylation of specific genes in CML,can potentially promote the development of novel targeted therapeutic strategies.Such strategies could transform into clinical practice,effectively aiding diagnosis and treatment of CML patients.

Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.

Objective:To investigate the influence of circ_BACH2 on the malignant biological behavior of papillary thyroid cancer and its molecular mechanism.Methods:Cancer tissues and paracancer tissues of 51 patients with papillary thyroid carcinoma from the Fourth Central Hospital of Tianjin between 2017 and 2019 were collected. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_BACH2, miR-370-3p and G protein coupled receptor kinase interacting factor 1 (GIT1) mRNA in tissues and cells; flow cytometry to detect cell apoptosis and cell cycle; plate clone formation experiment to detect the number of cell clones; cell counting kit 8 (CCK-8) to detect cell proliferation; Transwell array to detect cell migration and invasion; western blot to detect protein expressions; dual luciferase report experiment to detect the targeting relationship between circ_BACH2, miR-370-3p and GIT1; the nude mouse tumor formation experiment to detect the effect of circ_BACH2 on tumors in mice.Results:Compared with adjacent tissues, the expressions of circ_BACH2 and GIT1 in papillary thyroid cancer tissues was increased, while the expression of miR-370-3p was decreased. Compared with Nthy-ori3-1 cells, the expressions of circ_BACH2 in papillary thyroid cancer cells TPC-1 and SW579 were increased, the mRNA and protein levels of GIT1 were increased, miR-370-3p expression was decreased. The expression level of GIT1 mRNA was negatively correlated with that of miR-370-3p ( r=-0.634), and the expression level of circ_BACH2 was positively correlated with that of GIT1 ( r=0.635). The expression level of circ_BACH2 was negatively correlated with that of miR-370-3p ( r=-0.394, P＜0.05). Circ_BACH2 and miR-370-3p has a binding site at the 3' UTR of GIT1. After knocking down circ_BACH2, the proportion of G 0/G 1 cells in papillary thyroid cancer cells TPC-1 and SW579 was increased, the proportion of S-phase cells was decreased and the proportion of G 2/M-phase cells did not change significantly. The cell absorbance value was lower than that in si-NC group. The number of cell clone formation was decreased (43±5 vs 100±6, 54±8 vs 100±9); the cell apoptosis rate was increased [(19.60±2.40)% vs (4.30±0.20)%, (18.10±2.10)% vs (5.10±0.23)%]; cell migration number was decreased (61±7 vs 134±15, 58±6 vs 112±11), the invasion number was also decreased (45±6 vs 113±11, 47±4 vs 92±9); the expressions of Snail and Twist1 were decreased, and the expression of E-cadherin was increased ( P＜0.000). Inhibition of miR-370-3p expression reversed the effect of circ_BACH2 knockdown on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Overexpression of GIT1 reversed the effects of overexpression of miR-370-3p on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Mice injected with TPC-1 cells stably transfected with sh-circ_BACH2 showed a reduction in tumor volume [(535±91) mm 3 vs (857±114) mm 3] after 35 days of culture; tumor weight was decreased [(0.62±0.13) mg vs (1.06±0.15) mg, P＜0.05]; the expressions of circ_BACH2 and GIT1 were decreased, and the expression of miR-370-3p was increased in nude mouse tumor tissue. Conclusion:Silencing circ_BACH2 may inhibit the proliferation, migration and invasion of papillary thyroid cancer cells in vitro, promote cell apoptosis, and inhibit tumor growth in vivo through targeted regulation of miR-370-3p/GIT1.

Objective:To investigate the influence of circ_BACH2 on the malignant biological behavior of papillary thyroid cancer and its molecular mechanism.Methods:Cancer tissues and paracancer tissues of 51 patients with papillary thyroid carcinoma from the Fourth Central Hospital of Tianjin between 2017 and 2019 were collected. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_BACH2, miR-370-3p and G protein coupled receptor kinase interacting factor 1 (GIT1) mRNA in tissues and cells; flow cytometry to detect cell apoptosis and cell cycle; plate clone formation experiment to detect the number of cell clones; cell counting kit 8 (CCK-8) to detect cell proliferation; Transwell array to detect cell migration and invasion; western blot to detect protein expressions; dual luciferase report experiment to detect the targeting relationship between circ_BACH2, miR-370-3p and GIT1; the nude mouse tumor formation experiment to detect the effect of circ_BACH2 on tumors in mice.Results:Compared with adjacent tissues, the expressions of circ_BACH2 and GIT1 in papillary thyroid cancer tissues was increased, while the expression of miR-370-3p was decreased. Compared with Nthy-ori3-1 cells, the expressions of circ_BACH2 in papillary thyroid cancer cells TPC-1 and SW579 were increased, the mRNA and protein levels of GIT1 were increased, miR-370-3p expression was decreased. The expression level of GIT1 mRNA was negatively correlated with that of miR-370-3p ( r=-0.634), and the expression level of circ_BACH2 was positively correlated with that of GIT1 ( r=0.635). The expression level of circ_BACH2 was negatively correlated with that of miR-370-3p ( r=-0.394, P＜0.05). Circ_BACH2 and miR-370-3p has a binding site at the 3' UTR of GIT1. After knocking down circ_BACH2, the proportion of G 0/G 1 cells in papillary thyroid cancer cells TPC-1 and SW579 was increased, the proportion of S-phase cells was decreased and the proportion of G 2/M-phase cells did not change significantly. The cell absorbance value was lower than that in si-NC group. The number of cell clone formation was decreased (43±5 vs 100±6, 54±8 vs 100±9); the cell apoptosis rate was increased [(19.60±2.40)% vs (4.30±0.20)%, (18.10±2.10)% vs (5.10±0.23)%]; cell migration number was decreased (61±7 vs 134±15, 58±6 vs 112±11), the invasion number was also decreased (45±6 vs 113±11, 47±4 vs 92±9); the expressions of Snail and Twist1 were decreased, and the expression of E-cadherin was increased ( P＜0.000). Inhibition of miR-370-3p expression reversed the effect of circ_BACH2 knockdown on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Overexpression of GIT1 reversed the effects of overexpression of miR-370-3p on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Mice injected with TPC-1 cells stably transfected with sh-circ_BACH2 showed a reduction in tumor volume [(535±91) mm 3 vs (857±114) mm 3] after 35 days of culture; tumor weight was decreased [(0.62±0.13) mg vs (1.06±0.15) mg, P＜0.05]; the expressions of circ_BACH2 and GIT1 were decreased, and the expression of miR-370-3p was increased in nude mouse tumor tissue. Conclusion:Silencing circ_BACH2 may inhibit the proliferation, migration and invasion of papillary thyroid cancer cells in vitro, promote cell apoptosis, and inhibit tumor growth in vivo through targeted regulation of miR-370-3p/GIT1.

This paper reported a rare case of hypercalcemic crisis caused by a parathyroid adenoma with hemorrhage and cystic degeneration. Preoperative imaging examination of the patient was unable to determine the histological origin of the cervical cystic lesion. Despite aggressive medical treatment and hemodialysis, hypercalcemic crisis could not be relieved. Therefore, surgical exploration and excision of the cervical lesion were performed, and final diagnosis of parathyroid adenoma with hemorrhage and cystic degeneration was confirmed by pathology. Blood calcium level and renal function returned to normal after the surgery.

Objective:To analyze and evaluate the safety and efficacy of a Chinese domestically manufactured Heart Con-type implantable third-generation magnetic and hydrodynamic levitation left ventricular assist device(LVAD) for the treatment of end-stage heart failure(ESHF), by reporting the results of eleven-center clinical trial on 50 cases.Methods:This study was a multicenter clinical trial, designed by means of prospective, multicenter and single-group target value. 50 subjects with ESHF were competitively enrolled and treated with HeartCon as the LVAD in eleven centers. The primary efficacy measure was survival, defined as either the subjects experiencing the transition to heart transplantation(HT) or myocardial recovery assisted by the device within 90 days, or as successfully assisted by the LVAD for full 90 days after implantation. The target survival rate was 60%, other observations included implantation success rate, mortality, pump failure needing replacement or emergency heart transplantation.Results:All enrolled 50 patients received LVAD implantation successfully, 46 survived with the pump for 90 days, 1 patient transitioned to heart transplantation, and 3 patients experienced pump thrombosis, within which 2 patients underwent pump replacement and continued to live with the pump for 90 days, and the other one received emergency heart transplantation. There were no dropout subjects. The survival rate at full 90 days after HeartCon implantation was 100%. The survival rates with pump in the full set analysis and the protocol set analysis were 96.00% and 95.92% respectively, which were higher than the target value of 60%. The differences were both statistically significant( P<0.05). Conclusion:The results of the multicenter clinical trial with the largest sample size in China using domestically manufactured third-generation LVAD has demonstrated that, HeartCon is a safe and effective LVAD to treat ESHF patients.

Malignant tumors are one of the main causes of human death worldwide and pose a serious threat to human health. The current treatment methods are mainly the combination of chemotherapeutics， surgery， radiotherapy， or hormone therapy. The treatment process has limitations such as multidrug resistance， non-selective targeting of cancer cells， and drug toxicity. With the development and application of traditional Chinese medicine （TCM）， Chinese medicine has the characteristics of multi-angle and multi-mechanism coordination and slight toxic and side effects. It can effectively inhibit tumor proliferation， differentiation， and metastasis， and avoid drug resistance， serving as the focus of current tumor treatment research. Hedysari Radix， one of the genuine medicinal materials in Gansu province， is a tonic Chinese medicine with a wide range of pharmacological effects such as anti-inflammation， immune regulation， anti-oxidation， prevention and treatment of diabetic complications. In the majority of the ancient works on herbs of the past dynasties， Hedysari Radix was included under the item of Astragali Radix and used as Astragali Radix. Hedysari Radix is superior to Astragali Radix in enhancing immunity， scavenging free radicals， and resisting liver fibrosis. Studies have found that the effective components of Hedysari Radix have a prominent anti-tumor effect and a significant inhibitory effect on various malignant tumors such as liver cancer， bladder cancer， gastric cancer， breast cancer， and colorectal cancer. They can also combine with clinical anti-cancer drugs to reduce the toxic and side effects of chemotherapy drugs and improve the tolerance of patients during chemotherapy. On the basis of current research， this study summarized the mechanism of Hedysari Radix active components in inducing cell apoptosis， blocking cell cycle， inhibiting tumor cell proliferation， migration， and invasion， regulating micro mRNA （miRNA）， inducing cell autophagy， enhancing immune regulation， as well as reducing toxicity and enhancing efficiency and sensitization with clinical chemotherapeutics， and systematically explained the anti-tumor mechanism of Hedysari Radix active components， aiming to provide a basic reference for the further exploration of the anti-tumor mechanism of Hedysari Radix and the further development and utilization of its effective components.

Objective:To investigate the incidence of complications related to thread lift in the treatment of facial rejuvenation.Methods:The databases of China National Knowledge Infrastructure (CNKI), VIP Chinese Science and Technology Journal Full-text Database (VIP-CSJFD), Wanfang Data, China Biology Medicine (CBM), PubMed, The Cochrane Library and Embase were searched from database establishment to April 20, 2022. The inclusion and exclusion criteria were developed to include relevant studies that met the criteria. Two investigators independently performed literature screening and data extraction; the STROBE statement scored the quality of inclusion criteria for cross-sectional studies, the total score was 0-22 points, and the research of which score >11 points was considered as high-quality research; data analysis was performed using Stata16.0 software; Egger test and funnel plot analysis were used to evaluate the publication bias of literature.Results:Thirty-three articles involving 8 919 patients were included in this meta-analysis. The quality scores of 28 articles were > 11 points, and the remaining 5 articles were exactly 11 points, indicating that the overall quality of the articles was acceptable. The outcome measures of this meta-analysis included 11 indicators such as paresthesia, infection, facial asymmetry, facial nerve injury, mild unevenness or irregular contour, postoperative allergy, postoperative hematoma, pain, wire exposure or visibility, bruising, and swelling. The complication rates for each outcome measure were: paresthesia (1%), infection (0), facial asymmetry (2%), facial nerve injury (0), mild unevenness or contour irregularity (7%), postoperative allergy (0), postoperative hematoma (0), pain (17%), exposed or visible wire (7%), bruising (28%), swelling (55%). Egger test and funnel plot analysis showed that there was no publication bias in sensory abnormalities, facial asymmetry, postoperative allergy and pain. There may be some publication bias in the other 7 indicators.Conclusion:Among the complications related to thread lift, postoperative swelling, pain and bruising are the most common, while the incidence of serious complications is rare. Most complications are transient and self-resolving, and in general, thread lift is a relatively safe treatment modality.

Objective:To investigate the incidence of complications related to thread lift in the treatment of facial rejuvenation.Methods:The databases of China National Knowledge Infrastructure (CNKI), VIP Chinese Science and Technology Journal Full-text Database (VIP-CSJFD), Wanfang Data, China Biology Medicine (CBM), PubMed, The Cochrane Library and Embase were searched from database establishment to April 20, 2022. The inclusion and exclusion criteria were developed to include relevant studies that met the criteria. Two investigators independently performed literature screening and data extraction; the STROBE statement scored the quality of inclusion criteria for cross-sectional studies, the total score was 0-22 points, and the research of which score >11 points was considered as high-quality research; data analysis was performed using Stata16.0 software; Egger test and funnel plot analysis were used to evaluate the publication bias of literature.Results:Thirty-three articles involving 8 919 patients were included in this meta-analysis. The quality scores of 28 articles were > 11 points, and the remaining 5 articles were exactly 11 points, indicating that the overall quality of the articles was acceptable. The outcome measures of this meta-analysis included 11 indicators such as paresthesia, infection, facial asymmetry, facial nerve injury, mild unevenness or irregular contour, postoperative allergy, postoperative hematoma, pain, wire exposure or visibility, bruising, and swelling. The complication rates for each outcome measure were: paresthesia (1%), infection (0), facial asymmetry (2%), facial nerve injury (0), mild unevenness or contour irregularity (7%), postoperative allergy (0), postoperative hematoma (0), pain (17%), exposed or visible wire (7%), bruising (28%), swelling (55%). Egger test and funnel plot analysis showed that there was no publication bias in sensory abnormalities, facial asymmetry, postoperative allergy and pain. There may be some publication bias in the other 7 indicators.Conclusion:Among the complications related to thread lift, postoperative swelling, pain and bruising are the most common, while the incidence of serious complications is rare. Most complications are transient and self-resolving, and in general, thread lift is a relatively safe treatment modality.

Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently unclear. Here, we show that oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) promote the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of normal epithelial cells but delay their apoptosis. In addition, nuclear-cytoplasmic invaginations and multiple nucleoli are observed in sEV-treated normal cells, both of which are typical characteristics of premalignant lesions of OSCC. Mechanistically, miR-let-7c in OSCC-derived sEVs is transferred to normal epithelial cells, leading to the transcriptional inhibition of p53 and inactivation of the p53/PTEN pathway. In summary, we demonstrate that OSCC-derived sEVs promote the precancerous transformation of normal epithelial cells, in which the miR-let-7c/p53/PTEN pathway plays an important role. Our findings reveal that cancer cells can corrupt normal epithelial cells through sEVs, which provides new insight into the progression of OSCC.
Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell Transformation, Neoplastic ; Down-Regulation ; Epithelial Cells/metabolism* ; Extracellular Vesicles/pathology* ; Humans ; MicroRNAs/metabolism* ; Mouth Neoplasms/pathology* ; PTEN Phosphohydrolase/metabolism* ; Tumor Suppressor Protein p53/metabolism*