OBJECTIVE To investigate the improvement effects and mechanism of Achyranthes bidentata total saponins （ABS） extract on vascular endothelial dysfunction in spontaneously hypertensive rat （SHR） based on cytochrome P450 4A （CYP4A）/20-hydroxyeicosatetetraenoic acid （20-HETE）/G protein-coupled receptor 75 （GPR75） axis. METHODS Ten Wistar- Kyoto rats were taken as the normal control group. Forty SHR were first stratified by systolic blood pressure and then， within each stratum， randomly assigned using a random-number table to the model group （MOD group）， captopril positive control group （CAP group， 10 mg/kg）， ABS low- and high-dose extract groups （ABS-L group， ABS-H group， 60 and 120 mg/kg）， with 10 rats in each group. Animals in each group were given the corresponding drug or equal volume of pure water by gavage， once a day， for 28 consecutive days. After the last administration， systolic blood pressure of rats was measured. The levels of vasoactive substances， inflammatory factors and oxidative stress indicators in serum were measured. The pathological changes of rat thoracic aorta were observed. The level of reactive oxygen species （ROS） in aortic tissue was analyzed. The expressions of endothelial nitric oxide synthase （eNOS）， CYP4A， GPR75， nuclear factor-κB p65 （NF-κB p65）， phosphorylated NF-κB p65， p22phox， and reduced nicotinamide adenine dinucleotide phosphate oxidase 4（NOX4） in thoracic aorta tissue were detected. RESULTS After 28 d of treatment， compared with MOD group， the systolic blood pressure of rats in the ABS-L and ABS-H groups decreased significantly. The levels of 20-HETE， angiotensin Ⅱ， interleukin-1β， interleukin-6， tumor necrosis factor-α， intercellular cell adhesion molecule-1 and malondialdehyde in serum were significantly reduced （P＜0.05 or P＜0.01）， while the levels of nitric oxide， superoxide dismutase， glutathione peroxidase and catalase were significantly increased （P＜0.05 or P＜0.01）. Intimal damage of thoracic aorta was reduced， and endothelial cell morphology was improved. The expressions of ROS， CYP4A， GPR75， p22phox， NOX4 and the phosphorylation level of NF-κB p65 protein in thoracic aorta were down-regulated or reduced （P＜0.05 or P＜0.01）， while the expression of eNOS was up-regulated （P＜0.05 or P＜0.01）. CONCLUSIONS ABS extract may alleviate the inflammatory response and oxidative stress in SHR effectively by down-regulating the expression of CYP4A， reducing the production of 20-HETE， inhibiting the activation of GPR75， and subsequently suppressing the activation of downstream NF-κB and NOX4， thereby improving hypertension-related vascular endothelial dysfunction.

Megakaryocytes and hepatocytes are unique cells in mammals that undergo polyploidization through endomitosis in terminal differentiation. Many polyploidization regulators and underlying mechanisms have been reported, most of which are tightly coupled with development, organogenesis, and cell differentiation. However, the nature of endomitosis, which involves successful entry into and exit from mitosis without complete cytokinesis, has not yet been fully elucidated. We highlight that endomitosis is a new cell fate in the cell cycle, and tetraploidy is a critical stage at the bifurcation of cell fate decision. This review summarizes the recent research progress in this area and provides novel insights into how cells manipulate mitosis toward endomitosis. Endomitotic cells can evade the tetraploidy restrictions and proceed to multiple rounds of the cell cycle. This knowledge not only deepens our understanding of endomitosis as a fundamental biological process but also offers new perspectives on the physiological and pathophysiological implications of polyploidization.
Hepatocytes/physiology* ; Megakaryocytes/physiology* ; Humans ; Polyploidy ; Animals ; Cell Cycle/physiology* ; Cell Differentiation ; Mitosis/physiology*

In 2022, the National Cancer Center (NCC) of China reported the nationwide statistics of 2016 using population-based cancer registry data from all available cancer registries in China, which was mainly about the cancer incidence and mortality. Cancer remains a major health problem currently in our country and requires long term cooperation to deal with. This article provided a key point interpretation and analysis of cancer prevalence data in China, and provided an analysis of several main risk factors for cancer, which was conducive to the development of cancer prevention and control programs in different regions.

Objective:To investigate the difference in the proportions of T-lymphocyte subsets and the immunological monitoring profiles between patients with B-lymphoproliferative disorder(B-LPD) and healthy individuals.Methods:This clinical observational study involved 194 B-LPD patients [122 males, 72 females, average age (64±20)] treated in Qilu Hospital of Shandong University from May 14th, 2022 to January 19th, 2024. The patient cohort included 76 cases of chronic lymphocytic leukemia (CLL), 23 cases of diffuse large B-cell lymphoma (DLBCL), 17 cases of follicular lymphoma (FL), 12 cases of hair-cell leukemia (HCL), 10 cases of lymphoplasmacytic lymphoma/Waldenstr?m macroglobulinemia (LPL/WM), 26 cases of mantle cell lymphoma (MCL), 20 cases of marginal zone lymphoma (MZL), and 10 cases of unclassified CD5 -B lymphocytic proliferative disease unclassified (B-LPD-U). At the same time, 45 health control (HC) samples [22 males, 23 females, aged 62(±17)] from the medical examination center of our hospital in November 18th, 2023 were collected. The T cell subsets were meticulously analyzed using flow cytometry, including CD4 +naive T cell [CD4 +TN (CD3 +CD4 +CD45RA +CD62L +) ], CD4 +central memory T cell [CD4 +TCM (CD3 +CD4 +CD45RA -CD62L +) ], CD4 +terminally differentiated effector memory cells expressing CD45RA [CD4 +TEMRA (CD3 +CD4 +CD45RA +CD62L -) ], CD4 +effector memory T cell [CD4 +TEM (CD3 +CD4 +CD45RA -CD62L -) ], CD8 +TN (CD3 +CD8 +CD45RA +CD62L +), CD8 +TCM (CD3 +CD8 +CD45RA -CD62L +), CD8 +TEMRA (CD3 +CD8 +CD45RA +CD62L -), CD8 +TEM (CD3 +CD8 +CD45RA -CD62L -), naive regulatory T cell [nTreg (CD3 +CD4 +CD127 dim+CD25 +CD45RA +) ], memory Treg [mTreg (CD3 +CD4 +CD127 dim+CD25 +CD45RA -) ] and activated Treg [aTreg (CD3 +CD4 +CD127 dim+CD25 +HLA-DR +) ]. The difference of T cell subsets data were compared by Mann-Whitney test. Result:The proportionof CD3 +T cells within lymphocyte in B-LPD groups (CCL group 13.15%, DLBCL group 41.75%, FL group 30.52%, HCL group 34.24%, LPL/WM group 40.58%, MCL group 20.67%, MZL group 26.36%, CD5 -B-LPD-U group 17.49%) was significantly lower than HC group (64.85%). The percentage of CD4 +T cells in B-LPD groups (CCL group 46.63%, DLBCL group 40.76%, FL group 42.77%, HCL group 43.81%, LPL/WM group 43.02%, MCL group 45.58%, MZL group 43.95%, CD5 -B-LPD-U group 46.91%) was also significantly lower than HC group (54.61%). Conclusions:B-LPD diseases impair T cell immune function. The increased presence of CD4 +TEM, the reduced level of CD8 +TEMRA and the elevated aTreg suggest that B-LPD may suppress CD8 +T cell-mediated cytotoxicity and enhance the immunosuppressive activity of Treg.

Objective:To investigate the difference in the proportions of T-lymphocyte subsets and the immunological monitoring profiles between patients with B-lymphoproliferative disorder(B-LPD) and healthy individuals.Methods:This clinical observational study involved 194 B-LPD patients [122 males, 72 females, average age (64±20)] treated in Qilu Hospital of Shandong University from May 14th, 2022 to January 19th, 2024. The patient cohort included 76 cases of chronic lymphocytic leukemia (CLL), 23 cases of diffuse large B-cell lymphoma (DLBCL), 17 cases of follicular lymphoma (FL), 12 cases of hair-cell leukemia (HCL), 10 cases of lymphoplasmacytic lymphoma/Waldenstr?m macroglobulinemia (LPL/WM), 26 cases of mantle cell lymphoma (MCL), 20 cases of marginal zone lymphoma (MZL), and 10 cases of unclassified CD5 -B lymphocytic proliferative disease unclassified (B-LPD-U). At the same time, 45 health control (HC) samples [22 males, 23 females, aged 62(±17)] from the medical examination center of our hospital in November 18th, 2023 were collected. The T cell subsets were meticulously analyzed using flow cytometry, including CD4 +naive T cell [CD4 +TN (CD3 +CD4 +CD45RA +CD62L +) ], CD4 +central memory T cell [CD4 +TCM (CD3 +CD4 +CD45RA -CD62L +) ], CD4 +terminally differentiated effector memory cells expressing CD45RA [CD4 +TEMRA (CD3 +CD4 +CD45RA +CD62L -) ], CD4 +effector memory T cell [CD4 +TEM (CD3 +CD4 +CD45RA -CD62L -) ], CD8 +TN (CD3 +CD8 +CD45RA +CD62L +), CD8 +TCM (CD3 +CD8 +CD45RA -CD62L +), CD8 +TEMRA (CD3 +CD8 +CD45RA +CD62L -), CD8 +TEM (CD3 +CD8 +CD45RA -CD62L -), naive regulatory T cell [nTreg (CD3 +CD4 +CD127 dim+CD25 +CD45RA +) ], memory Treg [mTreg (CD3 +CD4 +CD127 dim+CD25 +CD45RA -) ] and activated Treg [aTreg (CD3 +CD4 +CD127 dim+CD25 +HLA-DR +) ]. The difference of T cell subsets data were compared by Mann-Whitney test. Result:The proportionof CD3 +T cells within lymphocyte in B-LPD groups (CCL group 13.15%, DLBCL group 41.75%, FL group 30.52%, HCL group 34.24%, LPL/WM group 40.58%, MCL group 20.67%, MZL group 26.36%, CD5 -B-LPD-U group 17.49%) was significantly lower than HC group (64.85%). The percentage of CD4 +T cells in B-LPD groups (CCL group 46.63%, DLBCL group 40.76%, FL group 42.77%, HCL group 43.81%, LPL/WM group 43.02%, MCL group 45.58%, MZL group 43.95%, CD5 -B-LPD-U group 46.91%) was also significantly lower than HC group (54.61%). Conclusions:B-LPD diseases impair T cell immune function. The increased presence of CD4 +TEM, the reduced level of CD8 +TEMRA and the elevated aTreg suggest that B-LPD may suppress CD8 +T cell-mediated cytotoxicity and enhance the immunosuppressive activity of Treg.

Objective To investigate the effect of the Notch signaling pathway on the proliferation and invasion of human SW982 synovial sarcoma cells. Methods SW982 cells and normal human synovial cells were routinely cultured, and the expression of proteins related to the Notch pathway was compared. The Notch signaling pathway was manipulated by NICD1 overexpression, CFB1 shRNA lentivirus, and the γ-secretase inhibitor, DAPT. CCK-8 and wound healing assays were carried out to investigate the role of the Notch signaling pathway in SW982 cells. Results The Notch signaling pathway clearly showed higher activity in human SW982 synovial sarcoma cells than in normal human synovial cells (P ＜ 0.05). The proliferation and invasion of SW982 cells were significantly upregulated by overexpressing NICD1; however, were suppressed by downregulating the Notch signaling pathway using CFB1 shRNA or DAPT (P ＜ 0.05). Conclusion Our findings demonstrate that the proliferation and invasion of human SW982 synovial sarcoma cells are dependent on Notch signaling pathway activity.

Objective This study was conducted to evaluate treatment-related toxicities,the patterns of failure,overall survival(OS)and progression-free survival(PFS)by comparing IFI with ENI in combination with chemotherapy. Methods Eligible patients were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. The primary end points wereacute treatment-related toxicities. The secondary end points were patterns of failure,OS and PFS. Kaplan?Meier survival rate of the method for calculating the Logrank test difference method. Results Between April 2012 and October 2016,a total of 228 patients were enrolled from nine centers in china. Grade≥3,Grade≥2 radiation esophagitis and pneumonitis in the IFI arm were significantly lower than that of the ENI arm(P=0.018,0.027).No significant differences were observed in overall failure rates,loco-regional failure,distant failure rates,in-field and out-field lymph node failure between the two arms(P=0.401,0.561,0.510,0.561,0.681).The 1-,2-, 3-,4-yearand median OS in the ENI arm and IFI arm were 84.1%,57.3%,39.4%,31.6%,28 months and 83.6%,62.1%,44.5%,31.5%,32 months(P=0.654),respectively. The 1-,2-,3-yearand median PFS in the ENI arm and IFI arm were 71.9%,42.3%,32.7%,20 months and 70.1%,45.0%,35.9%,22 months (P=0.885),respectively. Conclusions Compared to ENI,IFI resulted in decreased radiation pneumonitis and esophagitis without sacrificing loco-regional lymph nodal control,PFS and OS in thoracic ESCC. Clinical Trial Registry Chinese Clinical trail registry,registration number:NCT01551589.

Objective To investigate the role of Notch signaling pathway to maintain the stem cell-like characteristics of osteosarcoma and its underlying mechanism.Methods Lentiviral NICD1 or Numb-shRNA was transduced into MG63 osteosarcoma cells to activate Notch activity in vitro.The impact of Notch on osteosarcoma stem cells were assessed by the tumor sphere formation assay and flow cytometry analysis of cell surface markers STRO-1/CD117.The expression of stem cell related genes (Sox2,Oct4) were evaluated by Western blot and qPCR.The nude mice were randomly divided into 3 groups:the NICD1 overexpression (NICD-OE) group,the DAPT group and the control (CON) group.The tumor growth was monitored for 8 weeks and the tumor volume and weight were recorded weekly.To investigate whether Notch regulates Eph pathway,Eph pathway related protein EphB,pEphB was measured by Western blot.The impact of ephrinB 1 on NICD overexpression cell were assessed by tumor sphere formation assay.The expression of Sox2 and Oct4 was evaluated by Western blot.Results NICD1 overexpression or Numb-shRNA increased the activity of Notch pathway.The Notch-activated osteosarcoma showed enhanced in vitro tumor spheroid formation capacity,increased Stro-1/CD117double positive ratio,and upregulated expression of Sox2 and Oct4 in vitro.In animal experiments,it was found that activation of Notch pathway promoted tumor formation in vivo and Notch inhibition decreased it.The primary osteosarcoma cells were obtained from mice xenograft treated with DAPT and its tumor sphere formation capacity was significantly reduced.Finally,The Notch pathway inhibits the phosphorylation of EphB,as well as the downstream signal pathway of EphB,but there is no significant change in total EphB.The activation of Eph pathway inhibited Notch induced up-regulation of tumor sphere formation and Sox2 and Oct4 expression.Conclusion Notch signaling pathway maintains the stem cell-like characteristics of osteosarcoma probably by inhibiting the Eph pathway.

Objective: To investigate the efficacy and safety of anlotinib hydrochloride capsules for the treatment of advanced soft tissue sarcoma based on the data from Department of Bone and Soft Tissue Tumor, Peking University Cancer Hospital&Institute. Methods: Patients were randomized allocated at 2:1 ratio for the anlotinib treatment and placebo group. The treatment group received 12 mg/day of anlotinib for 14 consecutive days in a 21-day cycle. The primary end-point was progression-free survival (PFS), and the secondary end-points were disease control rate (DCR), overall survival (OS), and adverse event rate. Results: A total of 46 patients were enrolled in this study; 7 of them were excluded from per protocol set (PPS). Among the remaining 39 patients, 28 were included in the anlotinib group and 11 in the placebo group. In the anlotinib group, 4 patients had partial remission and 13 had stable disease (SD), whereas in the placebo group, 3 patients had SD. The difference in DCR between the 2 groups was statistically significant (60.7% vs . 27.3%, P=0.082). The DCR of the advanced soft tissue sarcoma in the anlotinib group was 78.6% (11/14). The median PFS in the anlotinib group was 12.4 (95% confidence interval [CI]: 7.6 to 17.2) months, which was significantly longer than 4 months in the placebo group (95% CI: 1.7 to 6.3 months, P=0.043); however, the difference in OS between the 2 groups was not significant (19.4 vs . 17.6 months, P=0.961). Regarding the safety, 2 patients had severe adverse events (7.14%) possibly related with treatment in the anlotinib group; one of them had pneumothorax. The other adverse events were grade 1 to 2. Conclusions: Soft tissue sarcoma is highly responsive to anlotinib, with prolonged PFS. Anlotinib is well tolerated and can be used as a treatment option for advanced soft tissue sarcoma.

Objective:To explore the outcome of soft tissue sarcoma (STS) on patients with soft tissue metastasis. Methods:We ana-lyzed 25 STS patients with soft tissue metastasis primarily localized on extremity and trunk. The study was conducted from June 2010 to June 2016 by retrospective analysis of the clinical and pathological characteristics of the patients. The assessed endpoints were overall survival. Results:Six patients (24%) had synchronous soft tissue metastasis, and 19 patients (76%) had metachronous metasta-sis. The average time for primary tumor recession of metastatic lesions was 45.3 months. Metastases were most common in parts of the trunk in 18 patients (72%), followed by the head and neck in 5 patients (20%). Eleven patients (44%) with lung metastasis had poor prognosis. Conclusion:STS occurred more rarely in soft tissue metastasis than in pulmonary metastasis. Neoadjuvant chemotherapy and surgical treatment were the major therapies employed. Targeted therapy as a new treatment rendered good results.