Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

Objective:To investigate the impact of bundled management of late-pregnancy induction strategies on induction time and maternal and perinatal clinical outcomes.Methods:This was a historical control study, including 61 pregnant women before the implementation of the bundled management strategies for induction protocol in September 2024, and 78 pregnant women after the implementation in December 2024, who received regular prenatal check-ups and finally admitted to Peking University Third Hospital for elective induction of labor at term. The rate of successful induction, the rate of reaching active phase, induction to labor length, duration of labor, hospital stay, and adverse maternal and preinatal outcomes and other information were compared between two groups. Logistic regression model was used to analyze the factors affecting the rates of successful labor induction and reaching active phase. Kaplan-Meier survival curves were plotted for induction to labor length and duration of labor, and the Cox proportional hazards regression model was used to analyze the impact of the bundled management strategies for induction strategies on the above indicators.Results:(1) Compared with the group before implementation, the group after implementation had a shorter induction to labor length (median: 47.4 vs 35.1 h), a shorter duration of labor (median: 14.0 vs 10.5 h), and a shorter hospital stay (median: 6 vs 4 d). The rate of successful induction increased [87% (53/61) vs 97% (76/78)], and the rate of reaching active phase increased [70% (43/61) vs 86% (67/78)]; the differences were statistically significant (all P<0.05). (2) Multivariate logistic regression analysis showed that the implementation of the bundled management strategies promoted successful induction ( OR=7.299, 95% CI: 1.189-44.800; P=0.032) and reaching active phase ( OR=2.640, 95% CI: 1.003-6.951; P=0.049). A pre-pregnancy body mass index<18.5 kg/m2 promoted successful induction ( OR=9.142, 95% CI: 1.154-72.423; P=0.036). (3) Kaplan-Meier curve analysis indicated that compared with the group before the implementation, the group after the implementation had a significantly shorter induction to labor length ( χ2=13.883, P<0.001) and a shorter duration of labor ( χ2=5.72, P=0.017). Cox proportional hazards regression analysis showed that the implementation of the bundled management strategies for induction protocol was a protective factor for shortening induction to labor length ( HR=1.806, 95% CI: 1.186-2.749; P=0.006) and duration of labor ( HR=1.677, 95% CI: 1.066-2.637; P=0.025). A cervical Bishop score >3 at admission was a protective factor for shortening the induction to labor length ( HR=1.627, 95% CI: 1.110-2.384; P=0.013), and parity was a protective factor for shortening the duration of labor ( HR=3.370, 95% CI: 1.806-6.288; P<0.001). Conclusions:By the implementation of the bundled management strategies for induction protocol, it is possible to promote successful induction of labor and reaching the active phase for pregnant women undergoing induction. This approach also shortens induction to labor length and the duration of labor, without increasing the risk of maternal and perinatal complications.

The incomplete degradation of tumour cells by macrophages(Mφ)is a contributing factor to tumour progression and metastasis,and the degradation function of Mφ is mediated through phagosomes and lysosomes.In our preliminary experiments,we found that overactivation of NADPH oxidase 2(NOX2)reduced the ability of Mφ to degrade engulfed tumour cells.Above this,we screened out liquiritin from Glycyrrhiza uralensis Fisch,which can significantly inhibit NOX2 activity and inhibit tumours,to elucidate that suppressing NOX2 can enhance the ability of Mφ to degrade tumour cells.We found that the tumour environment could activate the NOX2 activity in Mφ phagosomes,causing Mφ to produce excessive reactive oxygen species(ROS),thus prohibiting the formation of phagolysosomes before degradation.Conversely,inhibiting NOX2 in Mφ by liquiritin can reduce ROS and promote phagosome-lysosome fusion,therefore improving the enzymatic degradation of tumour cells after phagocytosis,and subse-quently promote T cell activity by presenting antigens.We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox,blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox,thereby inhibiting the activity of NOX2.This study elucidates the specific mechanism by which Mφ cannot degrade tumour cells after phagocytosis,and indicates that liquiritin can promote the ability of Mφ to degrade tumour cells by suppressing NOX2.

Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.

Objective:To investigate the impact of bundled management of late-pregnancy induction strategies on induction time and maternal and perinatal clinical outcomes.Methods:This was a historical control study, including 61 pregnant women before the implementation of the bundled management strategies for induction protocol in September 2024, and 78 pregnant women after the implementation in December 2024, who received regular prenatal check-ups and finally admitted to Peking University Third Hospital for elective induction of labor at term. The rate of successful induction, the rate of reaching active phase, induction to labor length, duration of labor, hospital stay, and adverse maternal and preinatal outcomes and other information were compared between two groups. Logistic regression model was used to analyze the factors affecting the rates of successful labor induction and reaching active phase. Kaplan-Meier survival curves were plotted for induction to labor length and duration of labor, and the Cox proportional hazards regression model was used to analyze the impact of the bundled management strategies for induction strategies on the above indicators.Results:(1) Compared with the group before implementation, the group after implementation had a shorter induction to labor length (median: 47.4 vs 35.1 h), a shorter duration of labor (median: 14.0 vs 10.5 h), and a shorter hospital stay (median: 6 vs 4 d). The rate of successful induction increased [87% (53/61) vs 97% (76/78)], and the rate of reaching active phase increased [70% (43/61) vs 86% (67/78)]; the differences were statistically significant (all P<0.05). (2) Multivariate logistic regression analysis showed that the implementation of the bundled management strategies promoted successful induction ( OR=7.299, 95% CI: 1.189-44.800; P=0.032) and reaching active phase ( OR=2.640, 95% CI: 1.003-6.951; P=0.049). A pre-pregnancy body mass index<18.5 kg/m2 promoted successful induction ( OR=9.142, 95% CI: 1.154-72.423; P=0.036). (3) Kaplan-Meier curve analysis indicated that compared with the group before the implementation, the group after the implementation had a significantly shorter induction to labor length ( χ2=13.883, P<0.001) and a shorter duration of labor ( χ2=5.72, P=0.017). Cox proportional hazards regression analysis showed that the implementation of the bundled management strategies for induction protocol was a protective factor for shortening induction to labor length ( HR=1.806, 95% CI: 1.186-2.749; P=0.006) and duration of labor ( HR=1.677, 95% CI: 1.066-2.637; P=0.025). A cervical Bishop score >3 at admission was a protective factor for shortening the induction to labor length ( HR=1.627, 95% CI: 1.110-2.384; P=0.013), and parity was a protective factor for shortening the duration of labor ( HR=3.370, 95% CI: 1.806-6.288; P<0.001). Conclusions:By the implementation of the bundled management strategies for induction protocol, it is possible to promote successful induction of labor and reaching the active phase for pregnant women undergoing induction. This approach also shortens induction to labor length and the duration of labor, without increasing the risk of maternal and perinatal complications.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.