ObjectiveTo investigate the potential mechanism of Huatan Sanjie Formula （化痰散结方， HSF） in the treatment of triple negative breast cancer （TNBC） based on the integrinβ1/focal adhesion kinase/yes-associated protein （integrinβ1/FAK/YAP） mechanotransduction signaling pathway. MethodsFifty BALB/c mice were randomly assigned to a model group， doxorubicin group， low-， medium-， and high-dose HSF groups， with 10 mice per group. An orthotopic TNBC transplantation model was established in all mice using syngeneic implantation of 4T1 cells. After successful modeling， mice in the model group received intragastric administration of normal saline 0.2 ml each day. Mice in the low-， medium-， and high-dose HSF groups received HSF by gavage at doses of 5.99， 11.97， and 23.94 g/（kg·d）， respectively. The doxorubicin group received intraperitoneal injections of doxorubicin （1.5 mg/kg） once every two days. All treatments lasted for 30 days. After the final administration， mice were sacrificed， and tumor weight and volume were measured. Hematoxylin-eosin （HE）， Masson's trichrome， and Sirius Red staining were performed to evaluate histopathological changes and collagen fiber deposition in tumor tissues. TUNEL staining was used to assess apoptosis. The Young's modulus of tumor tissues was measured using atomic force microscopy （AFM）. The nuclear-cytoplasmic localization of YAP was determined by immunofluorescence staining. Protein expression levels of integrinβ1， focal adhesion kinase （FAK）， YAP， and phosphorylated focal adhesion kinase （p-FAK） were detected by Western Blotting. The mRNA expression levels of integrinβ1， FAK， and YAP were assessed by quantitative real-time polymerase chain reaction （qRT-PCR）. Pearson correlation analysis was performed to evaluate the relationships among tumor tissue Young's modulus， apoptosis rate， and the expression levels of proteins related to the integrinβ1/FAK/YAP signaling pathway. ResultsCompared to the model group， tumor weight was significantly reduced in the doxorubicin group and the medium- and high-dose HSF groups， while tumor volume significantly decreased in the doxorubicin group and the high-dose HSF group （P＜0.01）. Tumor weight in the high-dose HSF group was significantly lower than that in the low-dose group， and tumor volume was significantly smaller than that in both the low- and medium-dose groups （P＜0.05）. Marked improvements in histopathological morphology were observed in the medium- and high-dose HSF groups and the doxorubicin group， while the proportion of collagen fiber deposition and the nuclear-to-cytoplasmic ratio of YAP were significantly reduced （P＜0.01）. Compared to the model group， all three HSF groups and the doxorubicin group exhibited significantly increased apoptosis rates， decreased Young's modulus， and reduced mRNA expression levels of integrinβ1， and YAP （P＜0.05 or P＜0.01）. Furthermore， protein expression levels of integrinβ1， p-FAK， and YAP in the high-dose HSF group were significantly lower than those in the model group （P＜0.05 or P＜0.01）. Pearson correlation analysis demonstrated a significant negative correlation between tumor tissue Young's modulus and apoptosis rate （r =-0.93， P＜0.01）. In contrast， the protein expression levels of integrinβ1， p-FAK， and YAP were positively correlated with Young's modulus （r=0.88， 0.97， and 0.98， respectively； P＜0.05） and negatively correlated with apoptosis rate （r=-0.93，-0.97， and -0.93， respectively； P＜0.05）. ConclusionHSF can significantly inhibit tumor growth in TNBC model mice. Its antitumor effect may be associated with reducing tumor tissue stiffness through suppression of the integrinβ1/FAK/YAP mechanotransduction signaling pathway.

The aging microenvironment, as a key driver of tumorigenesis and progression, plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype (SASP). SASP consists of a variety of interleukins, chemokines, proteases, and growth factors. It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms, thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment. Furthermore, these secreted factors activate key signaling pathways such as NF-κB, cGAS-STING, and mTOR, which regulate the expression of immune-related molecules (such as PD-L1) and promote the recruitment of immunosuppressive cells, including regulatory T cells and myeloid-derived suppressor cells. This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment. Furthermore, the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms, including approaches to inhibit SASP secretion or eliminate senescent cells. Although these strategies have shown promise in certain tumor models, the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies. This highlights the need for further research into adaptive stratification and personalized treatment approaches. Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.

Breast cancer (BC) is one of the most prevalent malignant tumors affecting women worldwide, with its incidence rate continuously increasing. As a result, treatment strategies for this disease have received considerable attention. Research has highlighted the crucial role of the Hedgehog (Hh) signaling pathway in the initiation and progression of BC, particularly in promoting tumor growth and metastasis. Therefore, molecular targets within this pathway represent promising opportunities for the development of novel BC therapies. This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC. By conducting a comprehensive review of various natural compounds, including polyphenols, terpenes, and alkaloids, we reveal both common and unique regulatory mechanisms that influence this pathway. This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC. Furthermore, by exploring the structure-activity relationships between these compounds and their molecular targets, we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway. These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics. Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

Breast cancer(BC)is one of the most prevalent malignant tumors affecting women worldwide,with its incidence rate continuously increasing.As a result,treatment strategies for this disease have received considerable attention.Research has highlighted the crucial role of the Hedgehog(Hh)signaling pathway in the initiation and progression of BC,particularly in promoting tumor growth and metastasis.There-fore,molecular targets within this pathway represent promising opportunities for the development of novel BC therapies.This study aims to elucidate the therapeutic mechanisms by which natural com-pounds modulate the Hh signaling pathway in BC.By conducting a comprehensive review of various natural compounds,including polyphenols,terpenes,and alkaloids,we reveal both common and unique regulatory mechanisms that influence this pathway.This investigation represents the first comprehen-sive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC.Furthermore,by exploring the structure-activity relationships between these compounds and their molecular targets,we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway.These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics.Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

Objective To investigate the relationship between the expression levels of serum multiple epithelial growth factor like domains 6(MEGF6),sterile alpha motif(SAM)domain,scr homology 3(SH3)domain and nuclear localization signals 1(SAMSN1)and acute lung injury(ALI)in patients with sepsis.Methods A total of 182 patients with sepsis(sepsis group)who were admitted to Huazhong University of Science and Technology Union Jiangnan Hospital from February 2021 to February 2024 were selected and divided into ALI group(n=60)and non-ALI group(n=122)according to whether they were complicated with ALI or not.80 healthy people who underwent physical examination during the same period were selected as the control group.Serum MEGF6 and SAMSN1 levels were detected by enzyme-linked immunosorbent assay(ELISA).Pearson correlation analysis was used to analyze the correlation between serum MEGF6,SAMSN1 and clinical indicators.Multivariate Logistic re-gression analysis was used to analyze the risk factors of sepsis complicated with ALI.The receiver operating characteristic(ROC)curve was used to analyze the value of serum MEGF6 and SAMSN1 in the evaluation of sepsis complicated with ALI.Results Serum MEGF6(37.52±7.87 ng/L)and SAMSN1(24.26±7.45 ng/L)in the sepsis group were lower than those in the control group(78.17±15.26 ng/L,62.31±14.12 ng/L),and the differences were statistically significant(t=28.397,28.477,all P<0.001).Serum MEGF6(29.22±7.64 ng/L)and SAMSN1(13.28±7.12 ng/L)in the ALI group were lower than those in the non-ALI group(41.60±7.90 ng/L,29.66±7.67 ng/L),and the differences were statistically significant(t=10.045,13.961,all P<0.05).Se-rum MEGF6 and SAMSN1 in patients with sepsis complicated with ALI were negatively correlated with APACHE II score and SOFA score(r=-0.811～-0.728,all P<0.05),and positively correlated with oxygenation index(OI)(r=0.689,0.640,all P<0.05).APACHE II score and SOFA score were risk factors for sepsis complicated with ALI.Serum MEGF6(OR=0.769,95%CI:0.612～0.965)and SAMSN1(OR=0.778,95%CI:0.617～0.980)were protective factors(Wald χ2=5.140,4.525,all P<0.05).The area under the curve(AUC)of serum MEGF6,SAMSN1 alone and combined in the evaluation of sepsis complicated with ALI were 0.840,0.811 and 0.903,respectively.The combined detection was greater than the single detection,and the differences were statistically significant(Z=4.602,4.318,all P<0.05).Conclusion The serum levels of MEGF6 and SAMSN1 in patients with sepsis are decreased,which are the influ-encing factors of sepsis complicated with ALI.The combined detection of the two has a high evaluation value for sepsis complicated with ALI.

Objective To investigate the relationship between the expression levels of serum multiple epithelial growth factor like domains 6(MEGF6),sterile alpha motif(SAM)domain,scr homology 3(SH3)domain and nuclear localization signals 1(SAMSN1)and acute lung injury(ALI)in patients with sepsis.Methods A total of 182 patients with sepsis(sepsis group)who were admitted to Huazhong University of Science and Technology Union Jiangnan Hospital from February 2021 to February 2024 were selected and divided into ALI group(n=60)and non-ALI group(n=122)according to whether they were complicated with ALI or not.80 healthy people who underwent physical examination during the same period were selected as the control group.Serum MEGF6 and SAMSN1 levels were detected by enzyme-linked immunosorbent assay(ELISA).Pearson correlation analysis was used to analyze the correlation between serum MEGF6,SAMSN1 and clinical indicators.Multivariate Logistic re-gression analysis was used to analyze the risk factors of sepsis complicated with ALI.The receiver operating characteristic(ROC)curve was used to analyze the value of serum MEGF6 and SAMSN1 in the evaluation of sepsis complicated with ALI.Results Serum MEGF6(37.52±7.87 ng/L)and SAMSN1(24.26±7.45 ng/L)in the sepsis group were lower than those in the control group(78.17±15.26 ng/L,62.31±14.12 ng/L),and the differences were statistically significant(t=28.397,28.477,all P<0.001).Serum MEGF6(29.22±7.64 ng/L)and SAMSN1(13.28±7.12 ng/L)in the ALI group were lower than those in the non-ALI group(41.60±7.90 ng/L,29.66±7.67 ng/L),and the differences were statistically significant(t=10.045,13.961,all P<0.05).Se-rum MEGF6 and SAMSN1 in patients with sepsis complicated with ALI were negatively correlated with APACHE II score and SOFA score(r=-0.811～-0.728,all P<0.05),and positively correlated with oxygenation index(OI)(r=0.689,0.640,all P<0.05).APACHE II score and SOFA score were risk factors for sepsis complicated with ALI.Serum MEGF6(OR=0.769,95%CI:0.612～0.965)and SAMSN1(OR=0.778,95%CI:0.617～0.980)were protective factors(Wald χ2=5.140,4.525,all P<0.05).The area under the curve(AUC)of serum MEGF6,SAMSN1 alone and combined in the evaluation of sepsis complicated with ALI were 0.840,0.811 and 0.903,respectively.The combined detection was greater than the single detection,and the differences were statistically significant(Z=4.602,4.318,all P<0.05).Conclusion The serum levels of MEGF6 and SAMSN1 in patients with sepsis are decreased,which are the influ-encing factors of sepsis complicated with ALI.The combined detection of the two has a high evaluation value for sepsis complicated with ALI.

Background::Rapid initiation of antiretroviral therapy (ART) is recommended by guidelines, however, real-world studies of same-day initiation of ART in China are limited, and an optimal treatment regimen has yet to be identified. The study aims to provide a realistic reference for rapid initiation of ART.Methods::We retrospectively analyzed the clinical data of treatment-na?ve people with human immunodeficiency virus (PWHs) who were diagnosed and prescribed same-day ART initiation from January 1, 2021 to December 31, 2022 at Chongqing Public Health Medical Center. PWHs voluntarily chose an ART regimen that divided them into two groups: National Free Antiretroviral Treatment Program (NFATP)-recommended regimens group (2 nucleoside reverse transcriptase inhibitors + non-nucleoside reverse transcriptase inhibitors/protease inhibitors) and bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) group. The primary endpoint was the virological outcome of the two groups for same-day ART initiation at 24 weeks and 48 weeks. The secondary endpoints included changes in CD4 counts, maintenance of the original ART regimen at 48 weeks, and lipid levels and renal function at 48 weeks.Results::A total of 255 PWHs were included in the study, including 131 (51.4%) in the NFATP group and 124 (48.6%) in the BIC/FTC/TAF group. The overall virological suppression rates at 24 weeks and 48 weeks were 78.2% (165/211) and 95.4% (207/217), respectively. At 24 weeks, the virologic suppression rate in the NFATP group was lower than that in the BIC/FTC/TAF group (65.3% [66/101] vs. 90.0% [99/110], P <0.001). The median increase in the CD4 count was 198.0 (126.0-300.0) cells/μL at 24 weeks, with 182.0 (108.0-245.0) cells/μL in the NFATP group and 219 (132.0-316.0) cells/μL in the BIC/FTC/TAF group ( P = 0.035). At 48 weeks, there was no significant difference in the virological suppression rate or CD4 count between the groups. The 48-week initial ART regimen retention rates and treatment retention rates were significantly higher in the BIC/FTC/TAF group than in the NFATP group (91.1% (113/124) vs. 71.8% (94/131), 99.2% (118/119) vs. 93.0% (120/129), respectively). In terms of safety, there were no significant changes from baseline in levels of creatinine, estimated glomerular filtration rate (eGFR), or lipids in either group at 48 weeks. Conclusions::ART initiation on the day of diagnosis is effective, safe, and feasible, with satisfactory rates of virologic suppression, 48-week initial ART regimen retention rates, and treatment retention rates in treatment-na?ve PWHs. In our study, the early virologic suppression rate, CD4 cell counts, and treatment retention of the BIC/FTC/TAF regimens were significantly better than those of the NFATP regimens.

Immunotherapy has become a common means of cancer treatment. In immunotherapy, PD-1/PD-L1 inhibitors have significant efficacy. Cancer and various opportunistic infections are common complications in patients with AIDS. Owing to the special immune situation of these patients, AIDS is regarded as an exclusion standard in most clinical trials for cancer immunotherapy, conferring immunotherapy difficulty in treating patients with AIDS. The popularity of effective antiretroviral drugs has prolonged the lifetime of people with AIDS. Therefore, exploiting the opportunity of using immunotherapy in AIDS with cancer is urgent.

Objective: Analysis of the effect of triggering receptor-1 expressed on myeloid cells (TREM-1) in nonalcoholic fatty liver disease (NAFLD) and the mechanism. Methods: The oleic acid-treated HepG2 cells were divided into model group, overexpression group, interference group A, interference group B and negative control group. The mouse model of NAFLD was generated and randomly divided into (nuclear factor-κB) NF-κB inhibition group, protein kinase B (AKT) inhibition group, knockout group A, knockout group B and control group. The expression of inflammatory factors and TREM-1 in liver tissue was detected by PCR, and fat accumulation was detected by oil red O staining. Western blotting was used to detect the expression of TREM-1 and signaling pathway proteins, and HE staining was used to detect liver tissue changes. Results: TREM-1 was up-regulated in liver tissue of NAFLD mice [(0.936±0.127) vs. (0.432±0.105)] and in oleic acid-treated HepG2 cells. In oleic acid-treated HepG2 cells, overexpression of TREM-1 increased inflammatory factor expression and increased lipid droplets; inhibition of TREM-1 expression decreased inflammatory factor expression, and lipid droplets decreased. Knockout of TREM-1 and inhibition of NF-κB in NAFLD mice reduced hepatocyte inflammatory factor expression and reduced liver damage; knockout of TREM-1 and inhibition of AKT reduced liver tissue lipids and drops accumulate. Conclusions The overexpression of TREM-1 in NAFLD mice liver tissue can regulate inflammatory factor expression and lipid droplets through NF-κB and AKT signal pathway. TREM-1 might be a potential therapeutic target of NAFLD.

Objective To study on chronic myelogenous leukemia on the basis of protein interaction network to further explore its development mechanism.Methods Chronic myelogenous leukemia-related genes were screened from Online Mendelian Inheritance in Man database (OMIM) of genetic.After text mining by Cytoscape software and Agilent Literature Search,the protein interaction networks of chronic myelogenous leukemia were established.Then the molecular complexes contained in the network were analyzed by Clusterviz plug.The biological pathways of molecular complexes were enriched based on DAVID.Results There were 79 chronic myelogenous leukemia genes in OMIM.The protein-protein interaction network of chronic myelogenous leukemia contained 638 nodes,1 830 edges and maybe 5 molecular complexes.Conclusions Pathways underlying complexes 1 are involved in cytokines and inflammation,cytokines-receptor binding,cytokine receptor signaling.Complexes 3 has relation to complex biological behavior of the tumors and other broad relevance,which can provide the bioinformatic foundation for further understanding the development mechanisms of chronic myelogenous leukemia.