Objective:To investigate the differences between the mental clips placed intraoperatively and the tumor bed's target volume delineation of seroma based on CT scanning during radiotherapy for breast cancer patients who received breast-conserving surgery in the persuit of a better solution to determine the tumor bed position.Methods:The clinical data of 13 patients with early breast cancer who received postoperative radiotherapy after breast-conserving surgery at Beijing Shijingshan Hospital and Beijing Shijitan Hospital of Capital Medical University from December 2020 to January 2022 were retrospectively analyzed. They all had surgical clips implanted during the surgery. The following methods were used to delineate the target volume of tumor bed, including gross target volume delineation of tumor bed based on the mental clips (GTVtb-Clip), the tumor bed's gross target volume delineation of seroma based on CT scanning (GTVtb-Seroma), and the combination of both (GTVtb-C+S). The volume, diameter on three coordinate axis, neutral point displacement and conformability of these delineation methods were compared.Results:The volume of GTVtb-Clip, GTVtb-Seroma and GTVtb-C+S was (25±10) cm 3, (38±17) cm 3, (49±20) cm 3, and the differences were statistically significant (all P<0.05). The diameter on X axis was (4.7±1.2) cm, (5.3±1.4) cm, (5.7±1.6) cm, respectively in GTVtb-Clip, GTVtb-Seroma and GTVtb-C+S; the diameter on Y axis was (4.6±1.7) cm, (5.0±1.6) cm, (5.7±1.7) cm, respectively in GTVtb-Clip, GTVtb-Seroma and GTVtb-C+S; the diameter on Z axis was (4.4±1.5) cm, (5.2±1.4) cm, (5.6±1.4) cm in GTVtb-Clip, GTVtb-Seroma and GTVtb-C+S. The differences in the diameter of GTVtb-Clip and GTVtb-C+S on X,Y, Z axis were statistically significant (all P<0.05); the differences in the diameter of GTVtb-Seroma and GTVtb-C+S on X, Z axis were statistically significant (all P<0.05); the difference in the diameter of GTVtb-Clip and GTVtb-Seroma on X axis was statistically significant ( P<0.05) .Neutral point displacement was (5.8±1.6) cm, (5.5±1.9) cm, (6.0±1.7) cm, respectively of GTVtb-Clip, GTVtb-Seroma, GTVtb-C+S, and the difference was not statistically significant ( P>0.05). Conformability of GTVtb-Clip and GTVtb-Seroma, GTVtb-Clip and GTVtb-C+S, GTVtb-Seroma and GTVtb-C+S was 0.412±0.112, 0.525±0.095, 0.774±0.112,respectively, and the differences were statistically significant (all P<0.05). Conclusions:During radiotherapy after breast-conserving surgery for breast cancer, compared with the single method, the combination of GTVtb-Clip and GTVtb-Seroma can better cover the real tumor bed, thus reducing the omission of tumor bed and recurrence rate. CT position should better take place at 4 to 8 weeks for patients receiving radiotherapy after breast-conserving surgery, and target volume of tumor bed will be delineated based on the postoperative changes of both mental clips and seroma.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

To investigate the material basis and mechanism of Liupao tea on preventing COVID-19 by network pharmacology and molecular docking.The active ingredients and targets of Liupao tea were searched through the literature and the TCMSP databases and the network between the two was built by Cytoscape 3.7.1.Then using GenCards platform to predict the disease targets,mapping the common targets between Liupao tea and disease.The common targets were imported into the STRING database for exploring the protein-protein interaction.Core targets were enriched by gene ontology (GO) enrichment analysis and KEGG (kyoto encyclopedia of genes and genomes) pathway enrichment analysis using DAVID database etc..Finally,the screened active components were docked with the receptor protein SARS-CoV-2 3CL hydrolase (Mpro).Six active ingredients of Liupao tea were screened,such as (-)-epigallocatechin gallate (EGCG),(+)-catechin,(-)-catechin gallate,α-spinasterol,pelargonidin chloride and squalene,and 156 targets were identified.Among them,there were 112 common targets and 38 core targets with COVID-19.GO enrichment analysis (P<0.01) involved lipopolysaccharide,cell response to hypoxia,etc..And the KEGG pathway enrichment analysis (P<0.01)was conducted to obtain the HIF-1,IL-17,T cell receptor and other signaling pathways associated with COVID-19.The results of molecular docking showed that the active ingredients of Liupao tea were well bound to the receptor protein Mpro.The active ingredients of Liupao tea may control HIF-1,IL-17,T cell receptors signaling pathways by binding Mpro hydrolase and acting on inflammation and immune related targets such as MAPK1,TNF to prevent COVID-19.The EGCG of Mpro activity was determined ,and the IC50 was 3.4 μmol/L,which confirmed that EGCG was a certain inhibition effect on Mpro.

Objective To investigate the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the pathogenesis of psoriasis by detecting the level of PCSK9 in the plasma of patients with psoriasis and evaluating its effect on the secretion of interferon gamma (IFN-γ) and interleukin-17A (IL-17A) by peripheral CD4+ T cells.Methods Totally,30 outpatients with psoriasis vulgaris and 30 healthy volunteers (controls) were enrolled from Hospital for Skin Diseases,Chinese Academy of Medical Sciences between February 2016 and December 2017.Of the 30 patients,16 were males,and 14 were females.Their age varied from 18 to 66 years,and the course of disease ranged from 1 month to 15 years.Peripheral venous blood samples were obtained from the patients and controls,and the plasma and was performed to measure mRNA expression of PCSK9 in the PBMC,and enzyme-linked immunosorbent assay (ELISA) to determine the concentration of PCSK9 in the plasma.Peripheral CD4+ T cells were isolated from the PBMC by magnetic bead method,and divided into 2 groups to be co-cultured with (experiment group) or without PCSK9 protein (control group).After 24-hour treatment,ELISA was conducted to detect the levels of IFN-γ and IL-17A in the culture supernatant.Statistical analysis was carried out by using two-sample t test for the comparison between the two groups,and Pearson correlation analysis for analyzing correlations between the plasma level of PCSK9 and psoriasis area and severity index (PASI) score in the patients with psoriasis.Results PCSK9 mRNA expression was undetected in the PBMC of the patients with psoriasis and controls.The plasma level of PCSK9 was significantly higher in the patients with psoriasis ([243.58 ± 11.91] μg/L) than in the healthy controls ([199.74 ± 31.09] μg/L,t =5.761,P ＜ 0.001).After co-culture of the peripheral CD4+ T cells from patients with PCSK9 protein,the levels of IFN-γ and IL-17A both significantly increased ([6 150.00 ± 212.13] ng/L,[1 532.00 ± 11.31] ng/L,respectively) compared with the control group co-cultured without PCSK9 protein ([4 650.00 ± 212.13] ng/L,[698.5 ± 266.58] ng/L,respectively;t =7.071,4.418 respectively,both P ＜ 0.05).IFN-γand IL-17A were undetected in the culture supernatant of CD4+ T cells from the healthy controls in the experiment group or control group.Conclusion The plasma level of PCSK9 increases in patients with psoriasis,which may be involved in the pathogenesis of psoriasis by activating peripheral CD4+ T cells.

Objective To investigate the mechanism of glycoprotein serglycin (SRGN) promoting metastasis of breast cancer cells and the possible mechanism of SRGN expression.Methods Real time quantitative polymerase chain reaction (PCR) and bioinformation retrieval were used to detect the expression of SRGN in lymph node metastasis and non-metastasis breast cancer.MDA-MB-231 shRNA and MCF-7-SRGN of breast cancer stable cell line were established by lentivirus shRNA interferencc and overexpression.Transwell assay was used to test the effect of SRGN on invasion and metastasis of breast cancer cell line in vitro.Western blot assay was used to detect the changes of epithelial-mesenchymal (EMT) related markers.The possible regulatory mechanism of SRGN expression was detected by Western blot assay.Results SRGN expression was significantly increased in lymph node metastasis of breast cancer in clinical specimens.SRGN interference inhibited the invasion and metastasis of tumor cells.SRGN promoted breast cancer cells EMT.Transforming growth factor β1 (TGFβ1) promoted the expression of beta SRGN transcription.Conclusions SRGN can induce the change of EMT in breast cancer cells and promote the invasion and metastasis of breast cancer cells.

BACKGROUND:Studies have shown that vacuum sealing drainage can accelerate wound healing through increasing the wound blood flow, but its influence on activated gelatinases in human chronic wound stil lacks corresponding research. OBJECTIVE:To observe the effect of vacuum sealing drainage on the activity of gelatinase during the healing of chronic wounds. METHODS:Total y 96 trauma patients admitted at the People’s Hospital of Hubei University of Medicine from April 2013 to January 2014 were divided into two groups:52 patients in chronic wound group were treated with vacuum sealing drainage and 44 in control group treated with wound drainage at 3 days after removal of breast cancer. In the chronic wound group, exudates from pressure sores and skin necrosis after removal of breast cancer were col ected as samples A and B;exudates from two cases of venous stasis ulcer were col ected as samples C and D;exudates from traumatic skin wounds col ected as sample E. RESULTS AND CONCLUSION:TLC analyzer showed that:after 15-day negative pressure therapy, activities of matrix metal oproteinase 2 in sample A with low activity of gelatinase, matrix metal oproteinase 9 in sample B, matrix metal oproteinase 2 and 9 in samples C, D, E were al increased significantly (P<0.05);however, the activities of matrix metal oproteinase 9 in sample A with high activity of gelatinases and matrix metal oproteinase 2 in sample B were reduced significantly after treatment (P<0.05). In addition, no significant difference was found in the activity of matrix metal oproteinase 2, matrix metal oproteinase 9 and activated gelatinase betweenthe chronic wound group and control group (P>0.05). These findings indicate that the variation of activated gelatinases activity in human chronic wounds may be the reason why the chronic wounds cannot be healed for a long time, but vacuum sealing drainage can regulate the activity of activated gelatinases in chronic wounds.

Objective:To investigate the expression of HIF-1α, HIF-2αand MT in human papillary thyroid carcinoma ( PTC) and the association of their expression with clinicopathological indicators .Methods:Immunohistochemistry was used to analyze the ex-pression of HIF-1α, HIF-2αand MT in 70 PTC samples .The correlations of HIF-1α, HIF-2αand MT expression with one another , and with several clinicopathological indicators were statistically analyzed .Results:In 70 PTC samples, the positive expression rates of HIF-1α, HIF-2αand MT were 52.86%(37/70), 50.00%(35/70) and 44.29%(31/70), respectively.HIF-1α, HIF-2αand MT expression had significant correlations with cervical lymph node metastasis (P=0.034, P=0.022, and P=0.032, respectively). Meanwhile, HIF-1αexpression had a positive correlation with HIF-2α(rs =0.258, P=0.031) and MT (rs =0.266, P=0.026). HIF-2αand MT expression were positively correlated (rs=0.259, P=0.030).Concomitant expression of any two or all of the three molecules had stronger correlation with lymph node metastasis than did each alone ( P=0.004 for HIF-1α/HIF-2α, P=0.024 for HIF-1α/MT, P=0.029 for HIF-2α/MT, P=0.017 for HIF-1α/HIF-2α/MT).Conclusion:HIF-1α, HIF-2αand MT expression in PTC samples have a closely correlation , which are related to cervical lymph node metastasis .Therefore, the expression of HIF-1α, HIF-2αand MT might be used as biomarkers for cervical lymph node metastasis of PTC .

Objective To evaluate the efficacy of PET-CT brain imaging and resting-state fMRI in preoperative localization of temporal lobe epileptic (TLE)focus.Methods PET-CT and resting-state fMRI were performed in 17 patients with refractory TLE,who then underwent surgical treatment.Seventeen healthy volunteers matched with gender and age were recruited as the control group.The resting-state fMRI images were post processed by SPM5 software.Regional homogeneity(ReHo) values of the whole brain and bilateral hippocampus were obtained and analyzed.PET-CT images were analyzed by visual analysis method and asymmetry index method and the standardized uptake value (SUV) of bilateral hippocampus were obtained.The ReHo values and SUV of the bilateral hippocampus were compared by two independent samples t-test,and analyzed by receiver operating characteristic curve (ROC) for optimized diagnostic threshold.Pearson correlation analysis was employed for evaluating the correlation between the SUV and ReHo values of bilateral hippocampus.The consistency between the diagnostic accuracy of PET-CT and resting-state fMRI was assessed by Kappa consistency test.The outcome of the patient group was compared with that of the control group,and with the pathological results,to evaluate the diagnostic value of the two modalities for preoperative localization of temporal lobe epileptic focus.Results Regional or comprehensive low metabolism of 18F-FDG in temporal lobes was presented in all 17 patients,and 11 patients out of 17 showed lateral decreased ReHo value.The diagnostic accuracy of the two examinations was 70.6％ (12/17) and 64.7％ (11/17) for PET-CT and resting-state fMRI respectively compared with pathological results,and could be increased to 76.5％ (13/17) when the two methods were combined for diagnosis.The ReHo values of the TLE group (0.34 ± 0.12)were significantly lower than those of the control group (0.46 ± 0.07) (t =3.230,P =0.003).The sensitivity and specificity of resting-state fMRI were 88.2％ and 94.1％ respectively when the ReHo value was 0.36.There was significant difference between the SUV of the affected (4.17 ±0.63) and healthy side(4.77 ±0.56) of hippocampus in TLE group(t =2.930,P =0.006).The sensitivity and specificity of PET-CT were 88.2％ and 64.7％ respectively when SUV was 4.23.The two values could be used as a threshold in the localization of temporal lobe epileptic focus.Consistency of lesion detection was revealed between PET-CT and resting-state fMRI though it was not high,and the Kappa value was 0.49.However,no correlation was detected between the SUV and ReHo value using Pearson correlation test(r =0.280,P =0.314).Conclusion Combined PET-CT brain imaging and resting-state fMRI as a multi-modality imaging method might improve the diagnostic accuracy of the TLE focus's localization.

For recent two decades,radiofrequency ablation technology(RFA)has made great progress in the field of the treatment for diseases for its distinguishing characteristic of microtrauma,targeted,effective and almost having no side-effect.At the very beginning,radiofrequency ablation was adopted in treating solid tumors,and since then it has been gradually practiced in treating benign diseases of solid organs such as hypersplenism,prostatic hyperplasia and widely used in almost every system of the body.Here,we review its therapic principle,types and clinical application.

Objective To investigate the apoptosis of gastric carcinoma SGC-7901 cell induced by histone deacetylase inhibitor(TSA)and to clarify its mechanisms.Methods The apoptosis-inducing role of TSA on gastric carcinoma SGC-7901 cell was investigated with the help of cell proliferation assay,Annexin V stain,cell flow analyzer and Tunel assay.Western blot,gene chips,real time PCR were employed to study the influence and mechanisms of TSA on the expression of gastric carcinoma cell SGC-7901 p53,bax,etc.Results TSA could induce the apoptosis of gastric carcinoma SGC-7901 cells,increase the expression of p53 and bax,and decrease the expression of bcl-2.survivin and easpase in gastric carcinoma SGC-7901 cells.TSA could transfer AIF and EndoG from mitochondria to nucleus.The apoptosis induced by TSA was brought about through the regulation of multiple apoptosis-related genes,and the apoptosis pathway induced by TSA was caspase-independent.Conclusion TSA can induce caspase-independent apoptosis in gastric carcinoma SGC-7901 cell through the regulation of multiple apoptosis-related genes.