ObjectiveTo investigate the efficacy and safety of stereotactic body radiotherapy （SBRT） combined with sintilimab and bevacizumab in the treatment of patients with unresectable hepatocellular carcinoma （uHCC） and related prognostic factors. MethodsA total of 42 patients with uHCC who underwent SBRT combined with sintilimab and bevacizumab in Department of Radiation Oncology， The Fifth Medical Centre of PLA General Hospital， from March to December 2022 were enrolled. The prescribed dose of planning target volume was 36‍ ‍—‍ ‍50 Gy in 5‍ ‍—‍ ‍6 fractions for continuous irradiation， followed by the regimen of sintilimab and bevacizumab. Each course of treatment was 3 weeks until the presence of tumor progression or serious adverse events. The Kaplan-Meier method was used to calculate overall survival （OS） rate and progression-free survival （PFS） rate， and the log-rank test was used for comparison between groups； the Cox proportional hazards model was used to investigate the influencing factors for prognosis. ResultsThe median follow-up time was 21.6 months， with an objective response rate of 69%， a disease control rate of 85.7%， a median PFS of 10.0 months （95% confidence interval ［CI］： 6.7‍ ‍—‍ ‍13.0）， and a median OS of 23.3 months （95%CI： 14.7‍ ‍—‍ ‍31.8）. Most adverse events were grade 1‍ ‍—‍ ‍2 events， and there were no fatal adverse events. At 6‍ ‍—‍ ‍8 weeks after treatment， the AFP response group had a significantly better OS than the non-AFP response group （not reached vs 11.8 months， P=0.007）. The multivariate analysis showed that AFP response was associated with the good prognosis of patients （hazard ratio=0.31， 95%CI： 0.13‍ ‍—‍ ‍0.75， P=0.009）. ConclusionFor patients with uHCC， SBRT combined with sintilimab and bevacizumab can improve survival with a manageable safety profile， and a >50% reduction in AFP at 6‍ ‍—‍ ‍8 weeks after treatment can be used as a potential prognostic indicator.

OBJECTIVES: We propose a new melanoma segmentation model, SG-UNet, to enhance the precision of melanoma segmentation in dermascopy images to facilitate early melanoma detection. METHODS: We utilized a U-shaped convolutional neural network, UNet, and made improvements to its backbone, skip connections, and downsampling pooling sections. In the backbone, with reference to the structure of VGG, we increased the number of convolutions from 10 to 13 in the downsampling part of UNet to achieve a deepened network hierarchy that allowed capture of more refined feature representations. To further enhance feature extraction and detail recognition, we replaced the traditional convolution the backbone section with self-calibrated convolution to enhance the model's ability to capture both spatial and channel dimensional features. In the pooling part, the original pooling layer was replaced by Haar wavelet downsampling to achieve more effective multi-scale feature fusion and reduce the spatial resolution of the feature map. The global attention mechanism was then incorporated into the skip connections at each layer to enhance the understanding of contextual information of the image. RESULTS: The experimental results showed that the SG-UNet model achieved significantly improved segmentation accuracy on ISIC 2017 and ISIC 2018 datasets as compared with other current state-of-the-art segmentation models, with Dice reached 92.41% and 86.62% and IoU reaching 92.31% and 86.48% on the two datasets, respectively. CONCLUSIONS The proposed model is capable of effective and accurate segmentation of melanoma from dermoscopy images.
Melanoma/diagnosis* ; Humans ; Neural Networks, Computer ; Dermoscopy/methods* ; Skin Neoplasms ; Image Processing, Computer-Assisted/methods* ; Calibration ; Algorithms

Objective:To investigate the effect and associated mechanism of tumor tissue-infiltrating NK cells after receiving radiotherapy for hepatocellular carcinoma (HCC).Methods:A HCC tumor-bearing mouse model was constructed using human hepatocellular carcinoma cell line (SK-Hep-1) and divided into four groups: control, radiotherapy, NK cell clearance, and NK clearance combined with radiotherapy. Tumor growth condition was simultaneously recorded. The NK cell ratio in peripheral blood and the NK cell intratumoral infiltration condition were detected by flow cytometry and immunohistochemistry. Lentiviral-constructed SK-Hep-1 cells was used to detect the effect of radiotherapy on the regulation of CXCL10 and NK cell chemotaxis following EZH2 overexpression. SK-Hep-1 cells were irradiated in vitro and in vivo. The expression levels of EZH2 and CXCL10 mRNA and protein in the two groups of cell lines and mouse tumor tissues were detected by reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), western blotting (WB), and immunohistochemistry. The chemotaxis and blocking experiments were used to validate the chemotaxis effect of CXCL10 on NK cells. The independent sample t-test was used to compare the groups. P<0.05 was considered statistically significant. Results:The HCC tumor-bearing mouse model experiment showed that HCC tumor growth was most remarkable in the NK clearance combined with the radiotherapy group compared to the radiotherapy group ( P<0.05). Compared with the control group, the number of NK cells in the peripheral blood of nude mice in the radiotherapy group was significantly reduced, while the NK cell intratumoral infiltration was significantly increased ( P<0.05). Flow cytometry and immunohistochemistry showed invitro and invivo expressional alterations. The average expression levels of EZH2 mRNA and protein in hepatocellular carcinoma cell lines and tumor tissues were decreased in the radiotherapy group than the control group and mouse tumor tissues ( P<0.05), while the mRNA and protein expression levels of CXCL10 increased ( P<0.05). The cell supernatant following radiotherapy enhanced NK cell chemotaxis but inhibited CXCL10 neutralization. EZH2 overexpression validated that radiotherapy up-regulated CXCL10 mRNA and down-regulated protein expression levels in in vitro and in vivo experiments ( P<0.05). The chemotactic effect on NK cells was significantly weakened with EZH2 overexpression following radiotherapy. Conclusion:NK cells, as immune effector cells, are directly involved in radiotherapy- activated anti-HCC immunity. Importantly, radiotherapy inhibits EZH2 expression in hepatocellular carcinoma, thereby upregulating CXCL10 expression and enhancing intratumoral NK cell invasion.

Objective To explore the possible mechanism of Bushen Qiangjin capsule on synovitis and fibrosis in knee osteoarthritis(KOA).Methods In the animal experiment,the animal model of KOA was established by anterior cruciate ligament transection(ACLT).The rats were randomly divided into blank group,model group,Bushen Qiangjin capsule group and celecoxib capsule group.The levels of interleukin-1β(IL-1β)and IL-18 in serum of rats in each group were detected by ELISA,and the histopathological changes of synovium of rats in each group were observed by HE and Sirius red staining.Immunohistochemical staining was used to observe the expression of NLRP3,Caspase-1,GSDMD,TGF-β and COL1A1 in synovium of rats in each group.In the cell experiment,Lipopolysaccharide(LPS)combined with Adenosine triphosphate(ATP)was used to stimulate rat-FLS to simulate OA inflammatory environment and induce pyroptosis model.The cells were treated with Bushen Qiangjin capsule or MCC950,and the levels of IL-1β and IL-18 in the cell culture supernatant of each group were detected by ELISA;the localization and expression of NLRP3,Caspase-1 and GSDMD were observed by immunofluorescence staining;and the mRNA and protein expression of NLRP3,Caspase-1,GSDMD,TGF-β,COL1A1,PLOD2 and TIMP1 were detected by RT-qPCR and Western Blot,respectively.Results The results of animal experiment showed that compared with the model group,Bushen Qiangjin capsule could significantly reduce the score of synovial histomorphology of KOA rats(P<0.01);significantly reduce the levels of IL-1β and IL-18 in serum of KOA rats(P<0.01);also reduce the expression of NLRP3,Caspase-1,GSDMD,TGF-β and COL1A1 protein in synovium of KOA rats(P<0.05,P<0.01).The results of cell experiment showed that compared with the model control group,Bushen Qiangjin capsule could significantly reduce the levels of IL-1β and IL-18 in the supernatant of cell culture(P<0.01);significantly reduce the relative fluorescence expression of NLRP3,Caspase-1 and GSDMD(P<0.01),and significantly reduce the expression of NLRP3,Caspase-1,GSDMD,TGF-β,COL1A1,PLOD2,TIMP1 mRNA and protein(P<0.01).Conclusion Bushen Qiangjin capsule could improve KOA synovitis and fibrosis by inhibiting the activation of NLRP3 inflammasome and regulating FLS pyroptosis.

ObjectiveTo evaluate the inter-rater and test-retest reliability of echo intensity of ultrasound image for quality of quadriceps femoris in patients with knee osteoarthritis (KOA). MethodsFrom March to December, 2021, 33 patients with unilateral KOA in Guangdong Provincial Second Hospital of Traditional Chinese Medicine were included. Ultrasound was used to observe the cross sections of rectus femoris (RF), vastus medialis (VM) and vastus lateralis (VL), and the images were saved. Two independent raters analyzed the average gray value of the picture with the Image J. One of the raters repeated the measurement. The intra-class correlation coefficient (ICC), standard error of measurement (SEM), minimum detectable change (MDC) and coefficient of variation (CV) were calculated and the Bland-Altman charts were drawn. ResultsThe gray value was higher in the RF, VM and VL in the affected side than in the healthy side (t > 2.262, P < 0.05). The inter-rater reliability was excellent, with ICC 0.982 to 0.995, SEM 1.60 to 3.82, CV 1.49% to 5.90%, and MDC value 4.43 to 10.59. The test-retest reliability of the rater was excellent, with ICC 0.969 to 0.990, SEM 2.37 to 5.41, CV 2.22% to 4.84%, and MDC value 6.57 to 15.00. Bland-Altman charts analysis showed that the consistency was good. ConclusionThe quadriceps femoris muscle quality is different between the affected and the healthy sides in patients with unilateral KOA. It is reliable to evaluate muscle echo intensity by Image J.

Objective:To investigate the mechanism by which chronic psychological stress aggravates intestinal barrier damage and promotes the development of enteritis through inhibiting Wnt/β-catenin pathway, so as to provide a new therapeutic strategy for the clinical diagnosis and treatment of inflammatory bowel disease (IBD).Methods:A comorbidity model of chronic psychological stress and enteritis was established using C57BL/6J mice. HE staining was used to analyze the effects of chronic psychological stress on the intestinal pathological damage in mice with enteritis. ELISA was used to detect the expression of proinflammatory cytokines. The ultrastructural changes of colonic cells and the state of intestinal mucus layer were observed under transmission electron microscope and scanning electron microscope. The secretion of mucoprotein 2 (MUC2) and the expression of cell proliferation marker Ki67 were detected by immunofluo rescence staining. The numbers of goblet cells were detected by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Western blot was performed to analyze the expression of tight junction protein between intestinal epithelial cells, β-catenin which was a key protein of Wnt/β-catenin pathway maintaining crypt proliferation, and downstream protein c-myc.Results:The sugar water consumption ratio decreased, but tail suspension immobility time, the swimming immobility time and the expression of corticotropin releasing hormone (CRH) in hypothalamus increased (all P<0.05) in the stress group as compared with those in the control group. Chronic psychological stress promoted weight loss and colonic shortening in mice with enteritis, exacerbated pathological damage and enhanced the release of pro-inflammatory factors. Moreover, increased disappearance of intestinal epithelial microvilli and severe cellular ultrastructural damage were also observed in the stress+ dextran sulfate sodium salt (DSS) group. There was no pathological damage in the control and stress groups. Chronic psychological stress aggravated intestinal barrier injury and inhibited intestinal barrier repair by inhibiting Wnt/β-catenin pathway. Conclusions:In the mouse model of DSS-induced enteritis, chronic psychological stress preconditioning inhibited the Wnt/β-catenin pathway, weakened the repair ability of intestinal epithelium, aggravated the loss of mucus layer of intestinal barrier and the damage of tight junction structure, and promoted the development of enteritis. In the absence of enteritis, chronic psychological stress had no significant effects on the Wnt/β-catenin pathway and the intestinal barrier.

ObjectiveTo test the inter-tester reliability and test-retest reliability of MyotonPRO for evaluating neck and shoulder muscle performance parameters in patients with unilateral chronic neck pain, observe the difference of muscle performance between the healthy and affected sides of patients with chronic neck pain, and analyze the factors that cause the imbalance of muscle performance in patients with chronic neck pain. MethodsFrom January to June, 2023, 32 patients with unilateral chronic neck pain in Guangdong Second Traditional Chinese Medicine Hospital were selected. Two testers used the same MyotonPRO equipment to measure the muscle tone, muscle hardness and muscle elasticity on both sides of the sternocleidomastoid muscle and the upper trapezius muscle in the relaxed position. Tester 1 repeated the measurement after an interval of 30 minutes, and Tester 2 was measured within the time interval between the two measurements of Tester 1. The intraclass correlation coefficient (ICC), standard error of mean (SEM) and minimum detectable change (MDC) were calculated simultaneously. The measurement results were plotted into Bland-Altman diagram and systematic bias analysis was performed. The difference in muscle characteristics between the affected side and the healthy side was compared. At the same time, the Visual Analogue Scale (VAS) score and body mass index (BMI) of the subjects were collected for correlation analysis. ResultsExcept the sternocleidomastoid muscle elasticity of the affected side (ICC = 0.697), the inter-tester reliability of all other parameters was high to very high (ICC = 0.719 to 0.952, SEM = 0.04 to 6.53, MDC = 0.12 to 18.11). The test-retest reliability of all parameters was high (ICC = 0.883 to 0.981, SEM = 0.03 to 5.72, MDC = 0.09 to 15.84). Bland-Altman plot analysis showed that the scatter distribution was consistent. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle were higher on the affected side than on the healthy side (t > 2.846, P < 0.05). The asymmetry index of tension, hardness and elasticity of upper trapezius muscle and sternocleidomastoid muscle was significantly positively correlated with VAS score and BMI (r > 0.385, P < 0.05). ConclusionMyotonPRO has good inter-tester reliability and retest reliability in evaluating the muscle performance of both sides of patients with chronic neck pain. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle on the affected side were higher than on the healthy side, and the difference of muscle performance was positively correlated with pain and BMI.

Dysregulation of histone deacetylases (HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors (HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.

【Objective】 To observe the effect of glutaraldehyde polymerized bovine hemoglobin injection (code: HSRP1) oxygen-carrying fluid on early perfusion of severe hemorrhagic anemia in rabbits. 【Methods】 The rabbit model of controlled severe hemorrhagic anemia was established. Twelve modeled rabbits were divided into glutaraldehyde polymerized bovine hemoglobin injection (code: HSRP1) group and sodium lactate ringer′s injection (LR) group, with 6 rabbits in each group(half male and half female). HSPR1 group and LR group were treated with HSRP1 and LR, respectively. The survival rate of experimental rabbits was observed, and the indexes of hemodynamics, venous blood gas, plasma hemoglobin, base surplus, lactic acid and bicarbonate were measured before and after blood loss, as well as each point within 24 h after infusion. 【Results】 The survival rate of HSRP1 group was significantly different from that of LR group (P<0.05); After exsanguination, the mean arterial pressure of each group was significantly different from that before exsanguination (P<0.05), but there was no significant difference between HSPR1 group and LR group after infusion; In the second stage of perfusion, the blood lactate concentration and base excess in the HSRP1 group were significantly different from those in the LR group at each time point (P<0.05), at 2 h after perfusion, the respiratory rate started to differ significantly from that of the LR group (P<0.05), heart rate was significantly different from LR group at 4 h after perfusion(P<0.05); There were no significant differences between HSRP1 group and LR group in plasma venous oxygen partial pressure, venous oxygen saturation and plasma hemoglobin at all time points. 【Conclusion】 HSPR1 is used for severe traumatic hemorrhagic shock in rabbits, and can improve the survival rate of experimental rabbits by providing oxygen to hypoxic tissues and correcting anaerobic metabolism. As a new oxygen-carrying fluid, HSPR1 can correct the oxygen supply balance of patients with severe hemorrhagicanemia in early stage.

Hemoglobin-based oxygen carriers(HBOCs) is a category of artificial blood substitute with efficient oxygen carrying and delivery functions. Due to the outstanding oxygen-carrying properties of HBOCs, the studies of expanding its clinical applications are undergoing rapidly. Studies have shown the efficacy of HBOCs in organ transplantation as machine perfusion solution in maintaining the organ metabolism or meliorating the margin donor organ quality with promising perspectives. This article aims to review the application status and prospect of HBOCs in organ transplantation in recent years.