Breast cancer (BRCA) possesses prominent molecular heterogeneity, where aberrant expression of genes annotated to asparagine metabolism networks drives malignant progression and therapeutic resistance. However, systematic construction of prognostic signatures from a holistic asparagine metabolic pathway perspective remains scarce, limiting the clinical translation of metabolic insights into prognostic tools. We integrated TCGA and GEO BRCA transcriptomic datasets to screen asparagine metabolism-related differentially expressed genes and build a prognostic model. Six biomarkers, SLC35A2, SRD5A2, NT5E, CEL, IFNG and CNR1, were selected via univariate Cox, LASSO and multivariate Cox regression. SRD5A2 and IFNG were enriched in low-risk patients, while the other four genes were upregulated in high-risk subgroups. This signature reliably stratifies patient prognosis, with risk scores correlating strongly with pathway activity, immune infiltration, immune checkpoints, mutation landscapes and drug responsiveness. Bioinformatic results were validated via TCGA cohort analysis, in vitro cellular assays and Western blot. Two in vivo models were established: 4T1 xenografts in 6-week-old BALB/c mice and DMBA/hormone-induced spontaneous breast tumors in 8-week-old SD rats. Tumors were generated by cell injection or DMBA gavage plus cyclic hormone treatment, and tissue sections were processed for immunohistochemistry. Consistent differential expression of the six core genes was validated across all in vitro and in vivo systems. In conclusion, this asparagine metabolism-associated signature offers candidate biomarkers for personalized prognosis and provides preclinical evidence for metabolism-targeted BRCA therapy.

Background: Pyroptosis, a pro-inflammatory programmed cell death process, is a key player in tumor biology, including in triple-negative breast cancer (TNBC). Inhibiting G9a has been proven to exert anticancer effects; however, the molecular mechanism of the effects remains unclear. The study aimed to illustrate whether inhibiting G9a can suppress the process of TNBC cells by promoting pyroptosis and investigate the underlying mechanisms. Methods: MCF-10A, MDA-MB-231 and SUM159PT cell lines were used for in vitro study. CCK8 and EdU staining assay were used to examine the cell proliferation, and flow cytometry assay was performed to evaluate cell death. Inflammatory factors were measured by ELISA kits. The mRNA and protein expression levels were analyzed by qRT-PCR, Western blot, and immunofluorescence staining. Transmission electron microscopy was used to observe the morphological changes in cells. Results: We found that knockdown of G9a suppressed the growth and the abilities of invasion and migration, induced pyroptosis, and increased the expression of RIG-I, p-STAT1, and GSDME of TNBC. Furthermore, a RIG-I inhibition Cyclo (Phe-Pro) partially rescued the activation of pyroptosis enhanced by knockdown of G9a. Conclusions: These findings indicate that inhibiting the function of G9a induces pyroptosis in TNBC cells by the RIG-1/STAT1/GSDME pathway, which provides a new therapeutic target for TNBC treatment.

Atractylodes lancea (Thunb.) DC (AL) has been extensively used in dietary health and clinical treatments due to its beneficial therapeutic effects on the gastrointestinal tract. In this study, we isolated and purified AL polysaccharide (ALP) and investigated its therapeutic efficacy in chemotherapy-associated gastrointestinal damage. The primary constituents of ALP, ALP-3, are predominantly composed of Glc and Fru, interconnected by →1)-β-D-fruf-(2→, with a minor proportion of β-D-Fruf-(2→, α-D-Glcp-(1→), which form the main chain, and a molecular weight of approximately 10.696 kDa. Then, the mice were subjected to cisplatin-induced gastrointestinal damage, and the protective effects of ALP-3 were evaluated in this model. We found that the ALP-3 possesses strong anti-inflammatory, antioxidant, and restorative properties in repairing the intestinal barrier. Additionally, ALP-3 significantly enhances the abundance of Lactobacillaceae and Lactobacilli, while simultaneously reducing the prevalence of Bacteroides and Escherichia-Shigella, and decreasing LPS-induced TLR4 activation. Our findings suggest that ALP-3 may be used as a preventive compound for preventing and ameliorating gastrointestinal damage induced by chemotherapy.

ETHNOPHARMACOLOGICAL RELEVANCE:Li-Chong-Xiao-Zhen granules (LCXZG) has the effect of " activate blood and resolve stasis," " soften hardness and dissipate binds " properties, and was widely used in the clinic for decades to treat uterine fibroids and ovarian cancer (OC), which is called "zheng jia" in traditional Chinese medicine. AIM OF THE STUDY:The aim of this study is to identify the active components of LCXZG and elucidate the mechanism of LCXZG in ovarian cancer by combining network pharmacology, metabolomics and proteomics. MATERIAL AND METHODS:The absorbed compounds in serum of LCXZG was identified by liquid chromatography-mass spectrometry. Network pharmacology was used to predict the active components and target genes of LCXZG. The therapy mechanism of LCXZG on OC were determined by establishing a nude mouse xenograft tumor model and using combined metabolomics and proteomics analysis. RESULTS:A total of 218 absorbed compounds in serum of LCXZG were identified by UPLC-MS. Network pharmacology results showed that lipid and atherosclerosis, chemical carcinoma-receptor activation and PI3K-AKT signaling were potential target pathways of LCXZG in the treatment of OC. Further metabolomics and proteomics studies demonstrated that LCXZG altered glycerophospholipid metabolism in ovarian cancer. CONCLUSIONS:This study demonstrated that most of the active Compound of LCXZG are Paeoniflorin, Turanose, Amygdalin and Benzoylpaeoniflorin, which may exert their anti-tumor effects by regulating glycerophospholipid metabolism in ovarian cancer.

OBJECTIVES:To investigate the molecular mechanism by which Lichong Xiaozheng Granules (LCXZ) sensitize ovarian cancer to cisplatin (DDP) treatment. METHODS:LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage. In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts, the effects of daily gavage of distilled water (control group), intraperitoneal injection of DDP (5 mg/kg) once a week, or both DDP injection and daily LCXZK gavage (15 g/kg) on tumor growth were evaluated. Histopathological changes in the xenografts and kidneys were assessed with HE staining. RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis. The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting. RESULTS:A total of 218 blood-borne components of LCXZ were detected by LC-MS. In the tumor-bearing mice, treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3% and 72.6% compared with that in the control group, respectively. Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups. Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3 (ANT3) with binding energies below -6 kcal/mol. Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice, and these changes were more pronounced in the combined treatment group. The expression levels of BAX, ANT3, cleaved caspase-3 and cleaved caspase-9 were increased, whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups. CONCLUSIONS:LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.

ETHNOPHARMACOLOGICAL RELEVANCE:Triple-negative breast cancer (TNBC), a highly aggressive subtype of breast cancer (BC), is more sensitive to ferroptosis than other subtypes. Xihuang pill (XHP) has been extensively used in Chinese clinical practice as an adjuvant therapy for TNBC. However, the underlying mechanisms of XHP in TNBC treatment remain incompletely elucidated. AIM OF THE STUDY:This study aimed to investigate the anti-TNBC activity of XHP and further clarify its underlying molecular mechanism. MATERIALS AND METHODS:An integrated strategy combining network pharmacology with UHPLC-QqQ-MS-based metabolomics was used to identify the active compounds and genes related to XHP that exert anti-TNBC effects by modulating ferroptosis-related protein ubiquitination modifications. In vivo, the therapeutic effects of XHP on TNBC were investigated via a subcutaneous xenograft model. In vitro, we evaluated the effects of XHP on the cell proliferative capacity following DCFH-DA, JC-1, and C11-BODIPY probes, transmission electron microscopy, Fe2+, MDA, and GSH assay kits were used to detect ferroptosis-related indicators. Potential mechanisms were assessed using western blotting, immunofluorescence, immunohistochemistry, and ubiquitination assays. RESULTS:OTUB1, SLC7A11, SLC3A2, and GPX4 were identified by network pharmacology in combination with UHPLC-QqQ-MS-based metabolomics as the key targets by which XHP exerts anti-TNBC effects by modulating ferroptosis-related protein ubiquitination modifications. β-boswellic acid, α-boswellic acid, deoxycholic acid, choline, chenodeoxycholic acid, and muscone were identified as key compounds. The experimental results demonstrate that XHP suppresses TNBC cell proliferation, invasion, and migration, safely inhibits tumour growth, with elevated Fe2+, LPO and ROS levels, and enhances GSH depletion and mitochondrial damage. Our results further confirmed that XHP exerts its anti-TNBC effects by inducing cell ferroptosis, as ferrostatin-1 was found to rescue XHP-induced inhibition of cell proliferation. Mechanistically, XHP promotes the degradation of SLC7A11 via the proteasomal pathway by suppressing OTUB1-mediated deubiquitination, thereby inducing system Xc-/GPX4 axis-dependent ferroptosis. CONCLUSIONS:Our study demonstrated that XHP may exert anti-TNBC effects partly by inhibiting OTUB1-mediated deubiquitination of SLC7A11, thereby inducing system Xc-/GPX4 axis-dependent ferroptosis. This study provides a foundation for developing potential products from XHP plant materials for the TNBC treatment.

Eleven undescribed piperidine alkaloids, arecachines A-J (1-11), were isolated from the peels of Areca catechu. Compounds 8-11 are featured as bis-piperidine alkaloids. Their structures were elucidated by analysis of UV, IR, HRESIMS, 1D and 2D NMR spectra. Compounds 1 - 4 , 6 , and 8-11 were evaluated for the monoamine oxidases (MAOs) inhibitory activity. Among them, compounds 3 , 4 , 6 , and 10 showed MAOA inhibitory activity with IC50 values of 7.85-55.96 mu M, while compounds 1 - 4 , 8 , 10 , and 11 showed MAOB inhibitory activity with IC50 values of 11.92-77.87 mu M.

Cinnamaldehyde (CA), a natural bioactive compound derived from Cinnamomum species, has demonstrated broad-spectrum antitumor activity. However, its therapeutic potential and precise mechanisms in ovarian cancer (OC) remain incompletely elucidated. In this study, we systematically investigated the inhibitory effects of CA on OC and the underlying molecular mechanisms through both in vitro and in vivo approaches. In vitro experiments demonstrated that CA significantly induces reactive oxygen species (ROS) accumulation in OC cells, activates mitochondria-mediated apoptosis, and induces mitochondrial autophagy via the AMPK/ULK1/Beclin1 signaling axis. These synergistic effects collectively lead to significant suppression of OC cell proliferation. In a murine xenograft model of OC, CA administration substantially inhibited the growth of heterotransplanted tumors. Further in vivo analyses revealed a significant increase in the number of apoptotic cells and upregulation of the expression of the autophagy markers LC3B, PINK1, and Parkin in tumor tissues. Concurrently, the expression of the autophagic substrate p62 and the mitochondrial membrane protein TOMM20 decreased. These findings consistently corroborated the cellular mechanisms observed in vitro. This study provides the first evidence that CA suppresses OC progression via ROS-mediated dual mechanisms: apoptosis induction and mitophagy activation. Our results underscore the translational potential of CA as a promising therapeutic candidate and provide a robust experimental foundation for its further development against OC.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV), is a life-threatening infectious condition. Acute lung injury is a common complication in patients with COVID-19. 3-chymotrypsin-like protease (3CL(pro)) of 2019-nCoV and neutrophil elastase are critical targets of COVID-19 and acute lung injury, respectively. Colchicine and magnolol are reported to exert inhibitory effects on inflammatory response, the severe comorbidity in both COVID-19 and acute lung injury. We thus designed and synthesized a series of novel colchicine-magnolol hybrids based on a two-step synthetic sequence. It was found that these novel hybrids provided unexpected inhibition on 3CL(pro) and neutrophil elastase, a bioactivity that colchicine and magnolol did not possess. These findings not only provide perquisites for further in vitro and in vivo investigation to confirm the therapeutic potentiality of novel colchicine-magnolol hybrids, but also suggest that the concurrent inhibition of 3CL(pro) and neutrophil elastase may enable novel colchicine-magnolol hybrids as effective multi-target drug compounds.

Objective Eugenol (EU) from cloves is highly effective against different tumors. The long noncoding ribonucleic acids (lncRNAs), which play a role of competing endogenous RNAs (ceRNAs), suppress microRNAs (miRNAs) involved in post-transcriptional regulatory networks. The present work focused on analyzing how EU affected pre-cancerous breast lesions (PBL). Methods Initially, the gene expression profiles of patients (n=880) in the National Center for Biotechnology Information (NCBI) database were analyzed. Further, we established a lncRNA-miRNA-mRNA ceRNA network through bioinformatics analysis and investigated mechanistic roles of lncRNAs as ceRNAs and the anti-tumor effect of EU using MCF-10AT cells in vitro as well as PBL model rats in vivo. Besides, Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), miR-383-5p, miR-9-5p, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor-A (VEGF-A) expression was examined through quantitative reverse transcription polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemical staining analyses. Results There were altogether 1162 mRNAs, 81 miRNAs, and 26 lncRNAs recognized as trend genes in breast cancer (BC) and pre-cancerous BC (pBC), constructing the ceRNA network using 3 lncRNAs, 3 miRNAs, and 38 mRNAs. It was observed that NEAT1, miR-383-5p, miR-9-5p, VEGF-A, and MMP-9 were downregulated in breast tumor cells in accordance with bioinformatics analysis. EU suppressed MCF-10AT cell growth, decreasing the NEAT1, VEGF-A, and MMP-9 levels and increasing miR-383-5p and miR-9-5p expressions in vitro and in vivo. Conclusion In summary, the EU reduced the VEGF-A and MMP-9 expressions via NEAT1-mediated miR-383-5p and miR-9-5p against PBL, indicating that the EU may be a promising external drug to act against PBL.

BACKGROUND:Sepsis-associated acute kidney injury (SA-AKI) is common and associated with poor outcomes in critically ill patients. Acetaminophen is often used as an antipyretic and analgesic drug, but the association of acetaminophen use with mortality and recovery of renal function in SA-AKI patients remain unclear. We aimed to investigate the association between acetaminophen use and outcomes in SA-AKI patients. METHODS:This is a retrospective cohort study based on the MIMIC-IV database. Adult patients with SA-AKI were included in the analysis. The exposure was acetaminophen use within 7 days after the onset of SA-AKI. The primary outcome was 28-day mortality. Secondary outcomes included ICU mortality, in-hospital mortality, 90-day mortality, 1-year mortality, and renal recovery. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) with 95% confidence interval (CI) for mortality. Logistic regression models were used to estimate the odd ratio (OR) with 95% CI for renal recovery. RESULTS:6752 patients with SA-AKI were included, and 3892 (57.6%) patients received acetaminophen. Acetaminophen use was associated with decreased 28-day mortality (HR 0.69, 95% CI 0.63-0.75), ICU mortality (HR 0.56, 95% CI 0.50-0.63), in-hospital mortality (HR 0.62, 95% CI 0.57-0.69), 90-day mortality (HR 0.73, 95% CI 0.68-0.79), and 1-year mortality (HR 0.62, 95% CI 0.57-0.69). Acetaminophen use also was associated with improved renal recovery (OR 1.15, 95% CI 1.04-1.28). CONCLUSIONS:Acetaminophen use is associated with decreased mortality and improved renal recovery in SA-AKI patients.

Metal nanoclusters (Me NCs) have become a research hotspot in the field of electrochemiluminescence (ECL) sensing analysis. This is primarily attributed to their excellent luminescent properties and biocompatibility along with their easy synthesis and labeling characteristics. At present, the application of Me NCs in ECL mainly focuses on precious metals, whose high cost, to some extent, limits their widespread application. In this work, Cu NCs with cathode ECL emissions in persulfate (S2O82-) were prepared as signal probes using glutathione as ligands, which exhibited stable luminescence signals and high ECL efficiency. At the same time, CaMnO3 was introduced as a co-reaction promoter to increase the ECL responses of Cu NCs, thereby further expanding their application potential in biochemical analysis. Specifically, the reversible conversion of Mn3+/Mn4+ greatly promoted the generation of sulfate radicals (SO4 center dot-), providing a guarantee for improving the luminescence signals of Cu NCs. Furthermore, a short peptide (NARKFYKGC) was introduced to enable the fixation of antibodies to specific targets, preventing the occupancy of antigen-binding sites (Fab fragments). Therefore, the sensitivity of the biosensor could be significantly enhanced by releasing additional Fab fragments. Considering the approaches discussed above, the constructed biosensor could achieve sensitive detection of CD44 over a broad range (10 fg/mL-100 ng/mL), with an ultralow detection limit of 3.55 fg/mL (S/N = 3), which had valuable implications for the application of nonprecious Me NCs in biosensing analysis.

A novel series of isopavine alkaloid reframidine with different substituent groups on the benzyl group of nitrogen was synthesised based on our reported enantioselective total synthesis route. These reframidine derivatives, 3b in particular, were found to provide anti-proliferative and pro-apoptotic activity against gastric cancer cells, which broadened the bioactivities beyond the traditional pharmacological neuroprotective properties of this kind of natural products.

Eight unprecedented monoterpenoid indole alkaloid (MIA) adducts and dimers, melofusinines A-H (1-8), and three undescribed melodinus-type MIA monomers, melofusinines I-K (9-11), together with six putative bioge-netic precursors were isolated from the twigs and leaves of Melodinus fusiformis Champ. ex Benth. Compounds 1 and 2 are unusual hybrid indole alkaloids incorporating an aspidospermatan-type MIA with a monoterpenoid alkaloid unit via C-C coupling. Compounds 3-8 feature the first MIA dimers constructed through an aspidospermatan-type monomer and a rearranged melodinus-type monomer with two different types of cou-plings. Their structures were elucidated by spectroscopic data, single crystal X-ray diffraction, and calculated electric circular dichroism spectra analysis. In addition, dimers 5 and 8 showed significant neuroprotection ef-fects on MPP +-injured primary cortical neurons.

Kaempferol has been suggested to be an effective anticancer agent in several malignant tumors. However, its function and mechanisms in breast precancerous lesions remain largely elusive. Here, we showed that kaempferol induced excessive mitochondrial fission and mitochondrial damage with activated mitochondrial fission factor (MFF)-mediated dynamin-related protein (DRP) 1 mitochondrial translocation. As a result, the PTEN-induced putative kinase 1 (PINK1)/Parkin signaling pathway was activated, accompanied by excessive mitophagy and reduced mitochondrial mass in cells. We also revealed that kaempferol-induced lethal mitophagy contributed to inhibiting breast precancerous lesion growth in vitro and in vivo. Furthermore, we verified serine/threonine kinase 11 (STK11/LKB1)/AMP-activated protein kinase (AMPK) pathway deficiency in breast precancerous lesions. Moreover, LKB1/AMPK pathway reactivation by kaempferol was required for excessive mitochondrial fission and lethal mitophagy. Taken together, our findings shed new light on the molecular mechanisms related to breast cancer prevention by kaempferol and provide evidence for its potential clinical application.

目的 研究卵巢癌动物模型的特点及应用现况,为当下卵巢癌模型的规范化制备提供参考指导.方法 通过从中国知网、万方、维普以及PubMed数据库中以"卵巢癌"和"动物模型"为主题词,PubMed数据库中检索建库至 2023 年 3 月 1 日的卵巢癌动物实验性期刊文献,均进行建库至今的文献搜索,共收集相关文献共 1428篇.从实验动物种类、年龄、实验造模方法、检测指标等方面进行总结,建立数据库进行系统分析.结果 筛选后共获得符合标准的实验性研究文献 178 篇.构建建立卵巢癌动物模型多选用BALB/c品种的雌性鼠;大部分周龄选择 4～6 周龄、6～8 周龄;造模方法使用最普遍的是异位移植,多接种在腋部皮下;在卵巢癌动物模型造模方法的使用上,以移植性模型使用最多,其中异位移植远高于原位移植的使用量;使用的细胞株或卵巢癌组织多为人源.检测指标检测最多的是肿瘤组织的外观指标、肿瘤病理及免疫组化.结论 卵巢癌动物模型在卵巢癌研究中应用广泛,但缺少专业规范的制备和评价标准,本文通过文献整理、数据归类分析,对卵巢癌的动物模型应用现状进行了详细分析,以期为构建规范化卵巢癌动物模型提供参考.实验多选用BALB/c品系鼠,以浓度为1×107/mL的人卵巢癌SKOV3 细胞注射于腋部皮下进行为期 10d异位移植造模,短时间内能获得大量模型,成瘤率高且个体差异小,可为研究卵巢癌提供参考.

Colchicine and its natural analogue (-)-N-acetylcolchinol methyl ether have been synthesized in a comparatively conciser asymmetric synthetic approach.Firstly, the carbon framework was constructed by Aldol condensation of simple aldehydes and ketones, and then the chiral amine intermediates were synthesized economically and efficiently through asymmetric reductive amination with chiral tert-butanesulfinamide.The 3-rings skeleton of colchicine and related alkaloids was then constructed by oxidation with hypervalent iodine reagent.Our strategy provides an efficient method for the convenient and economical synthesis of these alkaloids.

Breast cancer (BRCA) is the most diagnosed cancer worldwide and is responsible for the highest cancer-associated mortality among women. It is evident that anoikis resistance contributes to tumour cell metastasis, and this is the primary cause of treatment failure for BRCA. However, anoikis-related gene (ARG) expression profiles and their prognostic value in BRCA remain unclear. In this study, a prognostic model of ARGs based on The Cancer Genome Atlas (TCGA) database was established using a least absolute shrinkage and selection operator analysis to evaluate the prognostic value of ARGs in BRCA. The risk factor graph demonstrated that the low-risk group had longer survival than the high-risk group, implying that the prognostic model had a good performance. We identified 11 ARGs that exhibited differential expression between the two risk groups in TCGA and Gene Expression Omnibus databases. Through Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analyses, we revealed that the screened ARGs were associated with tumour progression and metastasis. In addition, a protein–protein interaction network showed potential interactions among these ARGs. Furthermore, gene set enrichment analysis suggested that the Notch and Wnt signalling pathways were overexpressed in the high-risk group, and gene set variation analysis revealed that 38 hallmark genes differed between the two groups. Moreover, Kaplan–Meier survival curves and receiver operating characteristic curves were used to identify five ARGs (CD24, KRT15, MIA, NDRG1, TP63), and quantitative polymerase chain reaction was employed to assess the differential expression of these ARGs. Univariate and multivariate Cox regression analyses were then performed for the key ARGs, with the best prediction of 3 year survival. In conclusion, ARGs might play a crucial role in tumour progression and serve as indicators of prognosis in BRCA.

Background: immunotherapy with immune checkpoint inhibitors (ICIs) for solid tumors had significantly improved overall survival (OS). Positive response to PD-1/PD-L1 blockades was observed in the treatment of solid tumors. Breast cancer (BC) patients are no exception. However, the efficacy of immunocheckpoint therapy in BC patients remains poor. A particularly important factor is the lack of studies on the expression patterns of immune checkpoints in BC patients. Methods：This article summarizes the expression of immune checkpoints such as PD-1, PD-L1, STAT1, CTLA-4 in BC, and analyzes the relationship between the expression of these immune checkpoints and OS.Results: It was found that increased expression of PD-1, PD-L1, STAT1, CTLA-4 was associated with poor OS in BC patients. In addition, co-expression of PD-L1 with PD-1, STAT1or CTLA-4 and co-expression of PD-1 with CTLA-4was related to poor OS. We analyzed associations between the proportionate expression of PD-L1 and PD-1, PD-L1 and STAT1, PD-1 and CTLA-4, PD-1 and LAG3, PD-L1 and CTLA-4 in BC patients, there was significance in correlation in both of the BC patients. Conclusions: our results suggest that transcriptome-based co-expression of STAT1 and PD-L1 is a predictor for poor OS in BC patients, which might provide novel insight into designing combinational targeted therapy for BC.

Background: Chronic heart failure (CHF) is the final destination of most cardiovascular diseases and the most important cause of death. The main clinical manifestations were pulmonary congestion and decreased cardiac output. The purpose of this systematic review is to evaluate the effectiveness of Yiqi Huoxue therapy on CHF. Methods: Seven electronic databases were searched to identify randomized controlled trials of Yiqi Huoxue (YQHX) method for CHF until April 30, 2020. The quality assessment of the included trials was performed by employing the Cochrane Risk of Bias tool and Jadad scale. Results: Nineteen randomized controlled trials were included in our review. Most of the included trials were considered as low quality. The aggregated results suggested that experimental group with YQHX therapy got better effect in increasing overall response rate (risk ratio, RR = 1.21, 95% confidence interval, CI 1.15–1.27), traditional Chinese medicine (TCM) syndrome response rate (RR = 1.26, 95% CI 1.17–1.36), 6-minute walk test (RR = 2.14, 95% CI 1.05–3.22), left ventricular ejection fraction (RR = 0.97, 95% CI 0.60–1.34), and stroke volume (standardized mean difference, SMD = 0.94, 95% CI 0.23–1.56), and in lowering down the TCM syndrome scores (SMD = –0.78, 95% CI –0.91 to –0.64), Minnesota Living with Heart Failure questionnaire (SMD = –1.01, 95% CI –1.56 to –0.45), 6-month readmission rate (RR = 0.50, 95% CI 0.28–0.89), B-type natriuretic peptide (SMD = –0.89, 95% CI –1.52 to –0.25), NT-proBNP (SMD = –2.07, 95% CI –3.34 to –0.08), and C-reactive protein (SMD = –2.04, 95% CI –4.12 to –0.67) as compared to using conventional Western medicine alone. There were no significant differences found in left ventricular end diastolic diameter and E/E′ between experimental groups and control groups. Moreover, the included sample capacity is small and the trails are all in Chinese. Quality of the evidence for outcomes were “low” and “very low” according to the GRADE assessment. Conclusion: YQHX is a valid complementary and alternative therapy in the management of CHF, especially in improving overall response rate, TCM syndrome response rate, 6-minute walk test, left ventricular ejection fraction, and stroke volume and in decreasing TCM syndrome scores, Minnesota Living with Heart Failure questionnaire, 6-month readmission rate, B-type natriuretic peptide, NT-proBNP, and C-reactive protein levels. Hence, YQHX is a relatively effective and safe therapy for CHF patients, which can be popularized and applied in the clinic. More long-term follow-up studies are still needed to substantiate and confirm the current findings.