Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

Objective:To study the antibacterial properties and in vivo and vitro biocompatibility of Cu-Fe-Zn alloy microfilament dressings, and to evaluate their wound healing promoting effect through clinical application.Methods:We evaluated the comprehensive antibacterial performance of dressings in vitro using plate counting method; After co culturing the extract of Cu-Fe-Zn alloy microfilament dressings with epidermal cells (HaCaT) and fibroblasts (NIH-3T3), their in-vitro biocompatibility was determined through the cell counting kit-8 (CCK-8) test; Further, Cu-Fe-Zn alloy microfilament dressing was applied to the wound surface of diabetes mice to test the biocompatibility of the material in vivo; Through a prospective randomized controlled trial, 50 burn and trauma patients admitted to the Burn and Plastic Surgery Department of the Third Xiangya Hospital of Central South University were selected and divided into an observation group of 25 patients and a control group of 25 patients. The observation group was treated with Cu-Fe-Zn alloy microfilament dressing, and the control group was treated with silver nanoparticle antibacterial dressing. The wound healing time and wound treatment effect of the two groups were compared.Results:The Cu 2+ release concentration of Cu-Fe-Zn alloy microfilament dressings detected by inductively coupled plasma-mass spectrometry (ICP-MS) was 1.3 μ g/ml, which had the effect of promoting the proliferation of HaCaT and NIH-3T3 cells (all P<0.05). The antibacterial rate of Cu-Fe-Zn alloy microfilament dressing against pseudomonas aeruginosa, escherichia coli and staphylococcus aureus reached 100%. The wound healing rate [(87.39±1.83)%] of diabetes mice treated with Cu-Fe-Zn alloy microfilament dressing was significantly higher than that of the control group [(58.66±3.54)%, P<0.05]. The inflammatory response of the wound tissue was relatively mild and the wound margin matrix was intact. The wound healing time of 25 patients treated with Cu-Fe-Zn alloy microfilament dressing [(23.52±10.02)d] was shorter than that of the control group [(40.84±21.22)d] ( t=17.159, P<0.001), and the overall treatment response rate of patients (96%) was significantly higher than that of the control group patients (64%) (χ 2=8.472, P=0.015). Conclusions:Cu-Fe-Zn alloy microfilament dressings have good antibacterial properties and biocompatibility, and have significant therapeutic effects on promoting wound healing. They not only effectively promote wound healing but also exert anti infection effects, and are expected to be a new type of wound repair dressing.

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.
Humans ; NF-kappa B/metabolism* ; Lipopolysaccharides/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Acute Lung Injury/metabolism* ; Lung ; Phosphate-Binding Proteins/therapeutic use* ; Pore Forming Cytotoxic Proteins/therapeutic use*

Chemically defined medium is widely used for culturing mouse embryonic stem cells (mESCs), in which N2B27 works as a substitution for serum, and GSK3β and MEK inhibitors (2i) help to promote ground-state pluripotency. However, recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs. Here, we demonstrated the deficient bone morphogenetic protein (BMP) signal in the chemically defined condition is one of the main causes for the impaired pluripotency. Mechanistically, activating the BMP signal pathway by BMP4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream targets Ube2s and Chmp4b. More importantly, BMP4 promotes a distinct in vivo developmental potential and a long-term pluripotency preservation. Besides, the pluripotent improvements driven by BMP4 are superior to those by attenuating MEK suppression. Taken together, our study shows appropriate activation of BMP signal is essential for regulating functional pluripotency and reveals that BMP4 should be applied in the serum-free culture system.
Animals ; Bone Morphogenetic Protein 4/metabolism* ; Cell Differentiation ; Chromosomal Instability ; Endosomal Sorting Complexes Required for Transport ; Mice ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Mouse Embryonic Stem Cells/cytology* ; Pluripotent Stem Cells/cytology* ; Signal Transduction ; Ubiquitin-Conjugating Enzymes

The tetanus has been eliminated in the pregnancy women and newborns in China. However, there is a gap for adult tetanus immunization, and the risk of tetanus infection cannot be ignored. In order to clearly understand the effect of the tetanus to human beings and the current use of tetanus immunological preparation for adult post-exposure prophylaxis, the incidence of the tetanus, the use status of tetanus immunological preparation and recommendations for post-exposure prophylaxis at home and abroad were reviewed and summarized, which may provide academic evidence for post-exposure prophylaxis procedures and use of tetanus immunological preparation.

The tetanus has been eliminated in the pregnancy women and newborns in China. However, there is a gap for adult tetanus immunization, and the risk of tetanus infection cannot be ignored. In order to clearly understand the effect of the tetanus to human beings and the current use of tetanus immunological preparation for adult post-exposure prophylaxis, the incidence of the tetanus, the use status of tetanus immunological preparation and recommendations for post-exposure prophylaxis at home and abroad were reviewed and summarized, which may provide academic evidence for post-exposure prophylaxis procedures and use of tetanus immunological preparation.

Objective:To develop a three-dimensional body image stimuli suitable for middle-aged people in China, and verify the validity and reliability of the body image stimuli.Method:According to China and World Health Organization body mass index classification standards of adults, a set of three-dimensional body image stimuli of Chinese middle-aged males and females with different body size was developed by using 3D Studio Max and Adobe Photoshop CC based on the literature and expert consultation method. Forty-two 45- and 59-year-old middle-aged people in Zhengzhou City, Henan Province were recruited to verify the three-dimensional body image stimuli. Through questionnaire survey and physical examination, the coincidence between the selected body type and the actual body type was tested; the body composition was measured by dual-energy absorptiometry (DXA), and the structure validity of the image was tested; the body size satisfaction was investigated by the body image stimuli and the standard questionnaire, and the empirical validity of the image was tested. The repeated survey was conducted 14 days after the initial survey, and three experts were invited to score the current somatotype of the subjects to test the test-retest reliability and inter-rater reliability of the body image stimuli. Pearson, Spearman, Kendall correlation and Kappa consistency analysis were used to evaluate the validity and reliability of the body image stimuli.Results:The average age of 42 subjects was 52.7 years old, including 13 males and 29 females. A group of three-dimensional body image stimuli of middle-aged men and women were developed, and each group included 8 images. 73.8% of the subjects chose the body size consistent with the actual body type, and the weighted Kappa coefficient was 0.755 ( P<0.01). The selected somatotype was positively correlated with body weight and body composition indexes such as fat content, and the Pearson correlation coefficient of construct validity was 0.623-0.717 ( P<0.05). The results of the two surveys were positively correlated, and the Spearman correlation coefficient of test-retest reliability was 0.784-0.821 ( P<0.05). The scores of the three experts on the current somatotype of the subjects were positively correlated, and the Kendall correlation coefficient of inter-rater reliability was 0.818-0.878 ( P<0.05). Conclusion:The development of principle and reference basis of three-dimensional body image stimuli of middle-aged people is reliable, and the validity and reliability of the body image stimuli are good.

Objective:To develop a three-dimensional body image stimuli suitable for middle-aged people in China, and verify the validity and reliability of the body image stimuli.Method:According to China and World Health Organization body mass index classification standards of adults, a set of three-dimensional body image stimuli of Chinese middle-aged males and females with different body size was developed by using 3D Studio Max and Adobe Photoshop CC based on the literature and expert consultation method. Forty-two 45- and 59-year-old middle-aged people in Zhengzhou City, Henan Province were recruited to verify the three-dimensional body image stimuli. Through questionnaire survey and physical examination, the coincidence between the selected body type and the actual body type was tested; the body composition was measured by dual-energy absorptiometry (DXA), and the structure validity of the image was tested; the body size satisfaction was investigated by the body image stimuli and the standard questionnaire, and the empirical validity of the image was tested. The repeated survey was conducted 14 days after the initial survey, and three experts were invited to score the current somatotype of the subjects to test the test-retest reliability and inter-rater reliability of the body image stimuli. Pearson, Spearman, Kendall correlation and Kappa consistency analysis were used to evaluate the validity and reliability of the body image stimuli.Results:The average age of 42 subjects was 52.7 years old, including 13 males and 29 females. A group of three-dimensional body image stimuli of middle-aged men and women were developed, and each group included 8 images. 73.8% of the subjects chose the body size consistent with the actual body type, and the weighted Kappa coefficient was 0.755 ( P<0.01). The selected somatotype was positively correlated with body weight and body composition indexes such as fat content, and the Pearson correlation coefficient of construct validity was 0.623-0.717 ( P<0.05). The results of the two surveys were positively correlated, and the Spearman correlation coefficient of test-retest reliability was 0.784-0.821 ( P<0.05). The scores of the three experts on the current somatotype of the subjects were positively correlated, and the Kendall correlation coefficient of inter-rater reliability was 0.818-0.878 ( P<0.05). Conclusion:The development of principle and reference basis of three-dimensional body image stimuli of middle-aged people is reliable, and the validity and reliability of the body image stimuli are good.

Objective The aim of this study was to investigate FFDM differential diagnosis between breast mastitis,benign hyperplasia and breast cancer. Methods Fifty-nine cases of non-puerperal breast mastitis,sixty-eight cases of benign hyperpla-sia and two hundred and forty cases with non-mass type breast cancer were analyzed retrospectively,which were verified by surgery and pathology by contrast with FFDM signs,pathological types,grouped and statistics processed. The observation indexes of lamellar shadow included shape,density and edge. The observation indexes of linear shadow included direction,form and diameter. Results The FFDM signs in three groups of breast diseases were statistically significant(P<0. 05):the form of linear shadow,accompanied by calcifications,the shape of lamellar shadow,the direction of linear shadow,the distribution of lesion,the sharp angle of shadow edge. χ2 segmentation show that there were significant differences between three groups(P<0. 0125):the shape of lamellar shadow,the direc-tion of linear shadow. Conclusion There have some values for the diagnosis of breast cancer by rigid form and radial distribution of linear shadow,rigid shape and segmental distribution of lamellar shadow,the polymorphic calcifications and the sharp angle sign.

AIM:To explore the effects of stanniocalcin 2 (STC2) on the proliferation, migration and the process of epithelial-mesenchymal transition (EMT) in human hepatocellular carcinoma HepG2 cells.METHODS:The expression levels of STC2 in the hepatocellular carcinoma cell lines and normal liver cells were assessed by Western blot.Colony formation assay was used to test the effect of STC2 on the proliferation of HepG2 cells.The effects of STC2 on the expression of proliferation-related molecules at mRNA and protein levels were determined by RT-qPCR and Western blot.The effect of STC2 on the migration ability was measured by Transwell assay.The mRNA and protein levels of vimentin and E-cadherin in STC2-overexpressing and-silencing cell lines were detected by RT-qPCR and Western blot.RESULTS:Compared with the normal liver cell line, the protein expression of STC2 was up-regulated in the hepatocellular carcinoma cell lines.The results of colony formation assay indicated that STC2 promoted the proliferation of HepG2 cells.STC2 significantly regulated the proliferation-related gene expression, such as cyclin D1.The results of Transwell assay showed that STC2 enhanced the migration ability of the HepG2 cells and influenced the EMT process.CONCLUSION:STC2 promotes the proliferation of HepG2 cells and affects the expression of proliferation-related genes.STC2 influences the process of EMT and promotes the migration of HepG2 cells.