The mechanisms underlying colorectal cancer liver metastasis (CRLM) remain incompletely understood. Increasing evidence suggests that stress-associated catecholamines may influence tumor progression. However, how norepinephrine (NE) influences the hepatic immune microenvironment during CRLM progression remains poorly characterized. In this study, we investigated the effects of NE on liver-resident macrophages during CRLM progression by integrating patient-based clinical analyses, single-cell transcriptomic profiling, and mechanistic in vivo and in vitro experiments. Clinically, patients with CRLM exhibited higher levels of psychological distress and increased circulating NE and CXCL12 compared with patients without liver metastasis. Anxiety scores were positively correlated with circulating NE and CXCL12. Single-cell RNA sequencing of CRLM lesions revealed macrophages as the predominant immune cell population with enriched expression of CXCL12, IL-10, and ADRB2, which encodes the β2-adrenergic receptor (β2-AR). In the hepatic context, this population was predominantly composed of Kupffer cells (KCs). In murine CRLM models, exogenous NE administration increased hepatic metastatic burden and KC accumulation, whereas selective KC depletion abrogated the pro-metastatic effects of NE. Mechanistically, NE promoted M2-like polarization of KCs in vitro through β2-AR-dependent activation of the PI3K/Akt pathway and altered their secretory profile. Consistently, NE-conditioned KCs enhanced colorectal cancer cell migration via CXCL12, an effect that was attenuated by pharmacological inhibition of β2-AR signaling or blockade of the CXCL12-CXCR4 axis. Overall, this study identifies a norepinephrine-driven neuroimmune mechanism in which β2-AR signaling reprograms KCs toward a pro-metastatic phenotype, thereby facilitating CRLM.

Background: Infectious arthritis is an uncommon but serious condition in older adults and may be easily misdiagnosed due to atypical clinical presentations. Proteus mirabilis is a rare causative pathogen of infectious arthritis, and its manifestations can resemble reactive arthritis, particularly in elderly patients with malignancy or immunocompromised status. Case Presentation: A 74-year-old woman with advanced endometrial cancer was admitted with fever and urinary tract infection caused by Proteus mirabilis, complicated by septic shock. After initial improvement with intravenous antibiotic therapy, she developed recurrent fever accompanied by bilateral knee swelling and pain. Reactive arthritis was initially suspected, and empiric glucocorticoid therapy resulted in transient symptomatic relief. However, magnetic resonance imaging of both knees demonstrated bone destruction consistent with infectious arthritis. Repeated joint irrigation combined with prolonged antibiotic therapy led to clinical improvement, resolution of fever, and recovery of knee function. Follow-up blood cultures were negative, and the patient remained clinically stable. Conclusion: This case highlights the diagnostic challenges of differentiating infectious arthritis from reactive arthritis in elderly patients with cancer. In older adults with Proteus mirabilis bacteremia who develop acute joint symptoms, infectious arthritis should be carefully considered, even when initial response to glucocorticoids is observed. Early imaging evaluation and repeated microbiological assessment are essential to avoid delayed diagnosis and improve outcomes in the aging population.

OBJECTIVE:To investigate the efficacy and safety of patients with primary intestinal lymphoma (PIL) who received either surgery first or chemotherapy first, aiming to provide robust evidence for clinical treatment. METHODS:We collected the medical records of 82 patients with PIL from 2011 to 2020 for retrospective study. The patients was divided into two groups: the surgery first group (surgery followed by chemotherapy, SF group) and the chemotherapy first group (chemotherapy followed by surgery or without surgery, CF group). RESULTS:The 3-year OS and 5-year OS of patients in SF group were higher than that in CF group (P < 0.05). Subgroup analysis showed that it had higher 5-year OS and 3-year OS in patients who were <60 years old, stage I-II, International Prognostic Index (IPI) score ≤2 or lymphoma located in the large bowel treated with SF compared to CF (P < 0.05). Univariate analysis revealed that patients <60 years old, with an IPI score of 1-2 and who underwent SF had a higher 5-year OS (P < 0.05). COX regression analysis demonstrated that age was an independent prognostic factor for OS (P = 0.006). The incidence of perioperative complications was lower in SF group than that in CF group (2.86 % vs. 36.17, P < 0.001). Univariate analysis and Multivariate logistic regression analysis both identified intestinal obstruction as the sole independent risk factor for surgery in CF group (P = 0.002). CONCLUSION:The patients with PIL who received SF had better prognosis and greater perioperative safety than those who received CF.

The purpose of this study was to identify whether the gut microbiota and metabolites of newly diagnosed acute myeloid leukemia (AML) patients displayed specific characteristic alterations and whether these changes could be used as potential biomarkers for predicting the disease. Notably, the gut microbiota and metabolites of AML patients exhibited significant structural and quantitative alterations at the time of their initial diagnosis. Beneficial bacteria, including Faecalibacterium, Collinsella, Lacticaseibacillus, and Roseburia, as well as butyric acid and acetic acid, were found to be considerably reduced in newly diagnosed AML patients. In contrast, Enterococcus and Lactobacillus, especially Enterococcus, were significantly enriched. Further investigation indicated that Enterococcus could serve as a potential intestinal marker, showing a strong negative correlation with the levels of acetic and butyric acid. Importantly, assays aimed at identifying AML demonstrated that Enterococcus, butyric acid, and acetatic acid exhibited excellent predictive effectiveness. Colonizing Enterococcus from patients were isolated for pathogen investigation, which revealed that these bacteria possess several strong virulence factors and multiple drug-resistance gene characteristics. Therefore, we speculate that the increase of Enterococcus may contribute to the development and progression of AML.

Abstract Umbilical cord mesenchymal stem cells (UC-MSC) transplantation has become a promising treatment for liver fibrosis. However, UC-MSC have limited anti-fibrosis ability for various reasons. In this study, we aimed to determine if the overexpression of CXCL9 in UC-MSC (CXCL9-UC-MSCs) could have synergistic anti-fibrosis effects and explore the possible mechanism. We analyzed the expression of α-SMA and Collagen-III in rats and LX-2 cells, as well as the inhibition of the TGF-β1/Smad3 pathway, approched by staining HE staining, immunohistochemistry staining, and western-blot. After the cell therapy, pathological staining and liver function indicated that the area of liver fibrosis in the rats were reduced, the hepatocellular necrosis and liver function damage were improved, and the improvement was more significant in the CXCL9-UC-MSC intervention group. Furthermore, the expression levels of α-SMA, Collagen-III, TGF-β1 and pSmad3 in the liver and LX-2 cells were decreased more obviously atfer the CXCL9 intervention. Meanwhile, the abilities of proliferation, viability and invasiveness of LX-2 cells were also significantly inhibited with the intervention of CXCL9. In conclusion, CXCL9 overexpression of UC-MSC inhibited the activation of TGF-β1/Smad3 signaling pathway, and reduced the expressions of α-SMA and Collagen-III in liver and LX-2 cells, thus playing a more significant anti-fibrosis effect.

Objectives:To evaluate the effect of Metformin therapy on patients of breast cancer with complications of Type-2 diabetes. Methods:Altogether 102 cases of breast cancer complicated with Type-2 diabetes admitted into Hebei General Hospital from January 2019 to December 2020 were included in the study. They were divided into two groups per whether Metformin was administered in the regimen, namely Metformin group and non-Metformin group. In the meanwhile, 106 cases of breast cancer without Type-2 diabetes admitted in the same period were selected to form a control group. Three groups were compared in terms of general data (incl. age, body mass, family history, menopause or not), clinical staging, tumor histological differentiation, molecular subtyping (Incl. Luminal A, Luminal B, ERBB2+, Basal-like) and prognosis. Results:Compared with the control group, Metformin group and non-Metformin group presented more patients with an older age and post-menopause state (P<0.05), but the latter two groups were not significantly different (P > 0.05). Patients in Metformin group and non-Metformin group had higher clinical staging and histological differentiation and more cases of Basal-like subtype than those in the control group (P < 0.05), without significant difference between those two groups (P > 0.05). More cases of local relapse, lymphatic and distant metastasis were seen in Metformin and non-Metformin groups, but the differences were not significant (P > 0.05). Both groups had lower 5-year survival rates than the control group (P < 0.05). Metformin group had a higher overall survival rate as well as a survival rate free of other lethal reasons than the non-Metformin group (P < 0.05) but was not significantly different from the control group in the survival rate free of other lethal reasons (P > 0.05). Conclusions:Type-2 diabetes remains one of the risk factors affecting breast cancer development, progress and prognosis, which could lower the 5-year overall survival rate among breast cancer patients. This is especially evident among menopaused women. Metformin therapy may improve the prognosis of patients of breast cancer complicated with Type-2 diabetes.

Background/Aims:This study aimed to explore the effect of gut microbiota-regulated Kupffer cells (KCs) on colorectal cancer (CRC) liver metastasis.Methods:A series of in vivo and in vitro researches were showed to demonstrate the gut microbiota and its possible mechanism in CRC liver metastasis.Results:Fewer liver metastases were identified in the ampicillin-streptomycin-colistin and colistin groups. Increased proportions of Parabacteroides goldsteinii, Bacteroides vulgatus, Bacteroides thetaiotaomicron, and Bacteroides uniformis were observed in the colistin group. The significant expansion of KCs was identified in the ampicillin-streptomycin-colistin and colistin groups. B. vulgatus levels were positively correlated with KC levels. More liver metastases were observed in the vancomycin group. An increased abundance of Parabacteroides distasonis and Proteus mirabilis and an obvious reduction of KCs were noted in the vancomycin group. P. mirabilis levels were negatively related to KC levels. The number of liver metastatic nodules was increased in the P. mirabilis group and decreased in the B. vulgatus group. The number of KCs decreased in the P. mirabilis group and increased in the B. vulgatus group. In vitro, as P. mirabilis or B. vulgatus doses increased, there was an opposite effect on KC proliferation in dose- and time-dependent manners. P. mirabilis induced CT26 cell migration by controlling KC proliferation, whereas B. vulgatus prevented this migration.Conclusions:An increased abundance of P. mirabilis and decreased amount of B. vulgatus play key roles in CRC liver metastasis, which might be related to KC reductions in the liver.

Background: A traditional Chinese medicine formula, Youdujing (YDJ) ointment, is widely used for treatment of human papilloma virus-related diseases, such as cervical cancer. However, the underlying mechanisms by which active compounds of YDJ alleviates cervical cancer are still unclear. Methods: We applied a comprehensive network pharmacology approach to explore the key mechanisms of YDJ by integrating potential target identification, network analysis, and enrichment analysis into classical molecular docking procedures. First, we used network and enrichment analyses to identify potential therapeutic targets. Second, we performed molecular docking to investigate the potential active compounds of YDJ. Finally, we carried out a network-based analysis to unravel potentially effective drug combinations. Results: Network analysis yielded four potential therapeutic targets: ESR1, NFKB1, TNF, and AKT1. Molecular docking highlighted that these proteins may interact with four potential active compounds of YDJ: E4, Y2, Y20, and Y21. Finally, we found that Y2 or Y21 can act alone or together with E4 to trigger apoptotic cascades via the mitochondrial apoptotic pathway and estrogen receptors. Conclusion: Our study not only explained why YDJ is effective for cervical cancer treatment, but also lays a strong foundation for future clinical studies based on this traditional medicine.

Umbilical cord mesenchymal stem cells (UC-MSCs) transplantation has become a promising treatment for liver fibrosis. However, UC-MSCs have limited anti-fibrosis ability, and their homing ability of UC-MSCs to the injured liver seems to be poor. In our study, we aimed to determine if the CXCL9-overexpressing UC-MSCs could have synergistic anti-fibrosis effects and whether it can promote the homing ability of UC-MSCs. Overexpression of CXCL9 in UC-MSCs (CXCL9-UC-MSCs) was attained by transfecting the lenti-CXCL9-mCherry to naive UC-MSCs. The therapeutic effect of transducted CXCL9-UC-MSCs on both repairing of hepatic fibrosis and target homing were evaluated by comparing with the control of UC-MSCs transfected with empty lenti-mCherry vector. The results revealed that the liver function of CXCL9-UC-MSCs treated group was significantly improved when compared with that of control UC-MSCs (P < 0.05), and the histopathology indicated an obvious decrease of the collagen fiber content and significant disappearing of pseudo-lobules with basically normal morphology of hepatic lobules. Furthermore, liver frozen sections confirmed that CXCL9-UC-MSCs have significantly stronger chemotaxis and stable persistence in the injured liver tissues. In summary, overexpression of CXCL9 could improve the efficacy of UC-MSCs therapy for liver fibrosis repairing on account of an enhanced ability of UC-MSCs in homing to and staying in the injured sites of liver fibrosis in rat models.

Silibinin is a flavonoid that improves fatty liver and insulin resistance. To elucidate the effect of silibinin on lipid deposition and the potential molecular mechanism, the present study conducted in vivo and in vitro experiments. In the in vivo experiments, mice were randomly divided into control, high-fat and silibinin groups, while HepG2 cells were randomly divided into control, palmitic acid intervention and silibinin intervention groups. The mRNA, protein and miR-122 expression associated with hepatic lipid metabolism were detected in each group. The results demonstrated that silibinin reduced the triglyceride content, miR-122 expression and the mRNA and protein expressions of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). Silibinin increased the mRNA and protein expression of carnitine palmitoyl transferase 1A (CPT1A). In the present study, HepG2 cells cultured with palmitate were treated with silibinin following overexpression of micro RNA (miR) 122. The results demonstrated that the mRNA and protein expression of FAS and ACC was increased, while that of CPT1A was decreased. Therefore, it could be deduced that silibinin improved lipid metabolism by reducing the expression of miR-122 and inhibiting the expression of miR-122 may be a new therapeutic target to improve fatty liver disease.

Colorectal cancer (CRC) is a common clinical malignancy globally ranked as the fourth leading cause of cancer mortality. Some microbes are known to contribute to adenoma-carcinoma transition and possess diagnostic potential. Advances in high-throughput sequencing technology and functional studies have provided significant insights into the landscape of the gut microbiome and the fundamental roles of its components in carcinogenesis. Integration of scattered knowledge is highly beneficial for future progress. In this study, literature review and information extraction were performed, with the aim of integrating the available data resources and facilitating comparative research. A knowledgebase of the human CRC microbiome was compiled to facilitate understanding of diagnosis, and the global signatures of CRC microbes, sample types, algorithms, differential microorganisms and various panels of markers plus their diagnostic performance were evaluated based on statistical and phylogenetic analyses. Additionally, prospects about current changelings and solution strategies were outlined for identifying future research directions. This type of data integration strategy presents an effective platform for inquiry and comparison of relevant information, providing a tool for further study about CRC-related microbes and exploration of factors promoting clinical transformation (available at: http://gsbios.com/index/experimental/dts_ mben?id=1).

Aims: This study aimed to investigate oxymatrine via regulating miR-182 improved the hepatic lipid accumulation in non-alcoholic fatty liver disease (NAFLD) model. Materials and methods: Wistar rats were fed high-fat and high-fructose diet (HFDHFr group) for 4 weeks and HepG2 cells were treated with palmitic acid (PA group), and then were given oxymatrine intervention. The expression profiles of miRNAs were accessed by RNA sequencing (RNA-Seq). Hematoxylin-eosin (HE) staining and Oil Red O staining were used to observe the inflammation and lipid accumulation in liver. The levels of sterol regulatory element binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty-acid synthase (FAS) and carnitine palmitoyltransferase 1A (CPT-1A) were detected by RT-qPCR and Western blotting, respectively. Cell viability was detected by Cell Counting Kit-8 (CCK-8). Key findings: miR-182 was down-regulated in the HFDHFr group and PA group. Oxymatrine reduced body weight, and improved glucose tolerance and insulin resistance in the HFDHFr + OMT group compared with HFDHFr group. In addition, oxymatrine reduced the ratio (liver weight/body weight), the content of trigly-cerides (TG), hepatic lipid accumulation and steatosis. The levels of SREBP-1c, ACC, and FAS were significantly decreased, while the CPT-1A level was obviously elevated after oxymatrine intervention (P < 0.05). In vivo, miR-182 knockdown increased the levels of SREBP-1c, ACC and FAS, while reduced the CPT-1A level. Additionally, oxymatrine attenuated the effects of miR-182 inhibitor on lipid accumulation. Significance: We presented a possible mechanism that oxymatrine alleviated hepatic lipid metabolism via regulating miR-182 in NAFLD model.

Therapeutic antibodies targeting PD-1 have made major breakthroughs in cancer treatment. However, the majority of colorectal cancer (CRC) cases are microsatellite stable (MSS) and do not respond to anti-PD-1-based immunotherapy. Combination therapy will be an ideal strategy to overcome this limitation. Gegen Qinlian decoction (GQD), a classical traditional Chinese medicine (TCM) formula, has been clinically proven to be effective in the treatment of ulcerative colitis (UC) and type 2 diabetes mellitus. Here, a systemic pharmacological study revealed that GQD acts through multiple targets and pathways in the human body. Combination therapy with GQD and anti-mouse PD-1 potently inhibited the growth of CT26 tumours in a xenograft model. Gut microbiota analysis revealed that combination therapy with GQD and anti-mouse PD-1 significantly enriched for s__Bacteroides_acidifaciens and s__uncultured_organism_g__norank_f__Bacteroidales_S24-7_group . Based on metabolomic analyses, profoundly altered metabolites were identified in the combination therapy group. Two metabolic signalling pathways, namely, glycerophospholipid metabolism and sphingolipid metabolism, were explored. In particular, we found that combination therapy with GQD and anti-mouse PD-1 significantly increased the proportion of CD8+ T cells in peripheral blood and tumour tissues. Direct treatment with GQD and anti-mouse PD-1 increased the expression of IFN-γ, which is a critical factor in antitumour immunotherapy. In addition, combination therapy with GQD and anti-mouse PD-1 downregulated PD-1 and increased IL-2 levels, suggesting that the combination therapy could effectively restore T-cell functions by suppressing inhibitory checkpoints. The application of the Chinese medicinal formula GQD with PD-1 blockade-based immunotherapy can be a novel therapeutic strategy for CRC patients with MSS tumours.

BACKGROUND:Sister Mary Joseph's nodule (SMJN) is rare and may occur independently or simultaneously with malignant tumors in the abdominal cavity. It has a poor prognosis. Endometrial carcinoma is the most common malignant tumor in the upper segment of the female reproductive tract; however, it rarely occurs with SMJN. We here report a case of endometrial carcinoma with SMJN.CASE SUMMARY:A 75-year-old woman was diagnosed with endometrial cancer > 2 years ago. After multiple cycles of chemotherapy, an obvious but painless umbilical mass was detected 2 wk before admission. The patient did not undergo surgical treatment but received chemotherapy, which was different from previous chemotherapy, for three consecutive cycles after discovery of umbilical metastases. Currently, the umbilical metastatic tumor has reduced, and the quality of life of the patient has significantly improved.CONCLUSION:Once the umbilical mass is found, the possibility of SMJN should be considered. We should also take into account the poor prognosis of endometrial carcinoma complicated with umbilical metastasis, especially in patients with advanced tumors, and it is important to choose an appropriate treatment.

BACKGROUND:Autophagy was recently regarded as a potential mechanism in nonalcoholic fatty liver disease. Silibinin (SIL), a natural flavonoid, has been used to prevent nonalcoholic fatty liver disease, however, the underlying mechanism is unclear. The aim of the present study was to explore the effect of SIL on hepatic steatosis and the possible link with autophagy.METHODS:The degree of hepatic steatosis in HepG2 cells was observed by oil-red O staining and triglyceride content. The effect of SIL on autophagy was tested by the Autophagy Detection Kit, and the expression of sterol regulatory element binding protein 1 (srebp-1), Fatty Acid Synthase (Fas), light chain 3, beclin-1, p62, AMP-activated Kinase (AMPK), and mammalian Target Of Rapamycin (mTOR) was examined by western blots.RESULTS:The lipid accumulation of HepG2 cells increased significantly in the high-fructose group compared to the control group. After SIL intervention, lipid accumulation was decreased. Using a fluorescence microscope, SIL was found to induce autophagy. Compared to control, the expressions of srebp-1, Fas, and phosphorylated-mTOR were increased by high-fructose, while the expressions of light chain 3 and beclin-1 decreased and srebp-1, Fas, and p62 were increased by autophagy inhibition. In contrast, opposite results were found in the SIL intervention group. The protein content of phosphorylated- mTOR was decreased, while phosphorylated-AMPK was increased in the SIL group compared to the high-fructose group.CONCLUSION:SIL can reduce lipid accumulation in HepG2 cells exposed to high-fructose by inducing autophagy. The AMPK/mTOR signaling pathway could be one of the underlying molecular mechanisms.

Background:Primary hepatic carcinoma (PHC) is the third commonest leading to cancer death around the world, and transarterial chemoembolization (TACE) has been proposed as the first-line therapeutic treatment for patients with unresectable PHC. This study aims to determine whether the combination of As2O3 and TACE is superior to alone TACE for achieving more clinical therapeutic efficacy, survival time, life quality and safety in patients with unresectable PHC.Methods:A comprehensive literature search was conducted on the clinical controlled trials comparing therapeutic effects of As2O3 & TACE versus alone TACE for unresectable PHC through English databases (including PubMed, Embase, and the Cochrane Library) and Chinese databases (including China Knowledge Resource Integrated Database, Wanfang Database, Weipu Database, and Chinese Biomedical Database). The last search was in 30 August 2017. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions. Primary outcomes, defined a priori, were therapeutic responses (clinical effective rate and clinical benefit rate), survival time, life quality, and adverse events of As2O3 & TACE compared with alone TACE expressed as relative risk (RR) with 95% confidence intervals (CI).Results:25 clinical controlled trials involving 1886 participants were included. We found that there were significant superiority associated with As2O3 & TACE compared with alone TACE in clinical benefit rate (RR: 1.24, 95% CI: 1.12-1.37), clinical effective rate (RR: 1.35, 95% CI: 1.17-1.55), 2-year survival rate (RR: 1.45, 95% CI: 1.20-1.75), and improving of KPS (RR: 1.31, 95% CI: 1.14-1.50). These associations were also observed in subgroups by intervened methods of As2O3 and pulmonary metastasis. Notably, the pooled relative risk of retention of sodium and water was obviously raised in patients with As2O3 & TACE therapy (RR: 16.616, 95% CI: 8.01 - 34.486).Conclusion:The superiority of adjuvant As2O3 therapy combined with TACE in PHC individuals will outweigh alone TACE therapy, especially in PHC populations with pulmonary metastasis.

Kushui rose (R. Setat x R. Rugosa) (KR) is a traditional Chinese medicine proven to be a potent antioxidant, and used for thousands of years. Approximately 30% of all human cancers relevant to mutational activated Ras, and over-activated Ras are accompanied by increased accumulation of reactive oxygen species (ROS). Thus, one way of developing anticancer drugs is to reduce ROS accumulation. Therefore, KR was predicted to have potential to combat over-activated Ras-related cancer. C. elegan with let-60(gf)/ra mutant, which exhibited tumor-like symptoms of the multivulva phenotype, was employed to determine the effect of KR on Ras/MAPK pathway. Other strains of worms and H2DCF-DA dye were also applied to study the antioxidant stress capacity of KR. This study was aimed to determine whether KR has a potential effect on combat over-activated Ras-related cancer through resistance to oxidative stress. Our results showed that Kushui rose decoction (KRD) has potent antioxidant activity in vitro, and can inhibit over-activated Ras in vivo Further, KRD significantly suppressed over-activated Ras/MAPK pathway by regulating oxidative stress-related proteins, such as forkhead transcription factor (DAF-16), glutathione S-transferase-4 (GST-4), superoxide dismutases (SODs) and heat shock protein-16.2 (HSP-16.2). However, essential oil and hydrosol of KR had no effect on over-activated Ras. Thus these results reminded us that people usually soak rose in hot water to prepare 'rose tea' as an effective way for health care. Thus, KRD was demonstrated to be a potential drug candidate for combating over-activated Ras-related cancer as an antioxidant.

PURPOSE:To investigate the expression of ANXA3 in breast cancer tissues and normal breast tissues and its relationship with the clinicopathological features.METHODS:The expression levels of ANXA3 mRNA and protein were determined by fluorescent quantitative RT-PCR and Western blot, respectively, in 81 samples from breast cancer tissues and normal breast tissues. Flow cytometry, used to detect the cell cycle, further analyzed the differences in the cell proliferation indexes between cancer and the normal tissues. In addition, the correlation between the gene and protein expression levels of ANXA3 and the cell proliferation indexes in breast cancer tissues was calculated.RESULTS:The expression levels of ANXA3 mRNA and protein were significantly higher in breast cancer tissues than in control samples. Furthermore, their expression patterns were significantly different in patients with different axillary lymph node metastasis states, with or without vascular tumor thrombus, and with different molecular classifications. The expression of ANXA3 mRNA and protein in patients with triple-negative breast cancer was significantly higher than in Luminal A and B types. However, no significant differences were detected in the expression levels in other subtypes. Compared to normal tissues, the cell proliferation indexes of breast cancer tissues were significantly higher, and presented significant positive correlations with the ANXA3 gene and protein expression levels.CONCLUSION:The expression of ANXA3 might play a crucial role in promoting the occurrence, development, and metastasis of breast cancer. It could serve as an important marker involved in the invasion and metastasis states, and the prognosis of breast cancer.

Realgar (As4S4), as a mineral drug containing arsenic compound, has been employed in clinical therapy of cancer for its good therapeutic reputation in Chinese traditional medicine. However, large dose of realgar and long period of treatment are necessary for achieving the effective blood medicine concentration due to its low bioavailability resulted from poor solubility. In this study, we obtained realgar transforming solution (RTS) using intrinsic biotransformation in microorganism, and investigated underlying mechanisms of RTS for HepG2 cells. Our results demonstrated that an effective biotransformation of realgar method by A. ferrooxidans was established, in which realgar was biologically converted into an aqueous solution, and RTS had a strong activity inducing apoptosis and interrupting G2/M progression in HepG2 cells via upregulation of cellular ROS. Importantly, RTS inhibited the cellular antioxidant defense system leading to abundant ROS accumulation, and activated cell cycle arrest and mitochondrial pathway of apoptosis mediated by activating p53 due to cellular uncontrolled ROS. Collectively, our findings suggest that RTS is a potential candidate for therapy of human hepatocellular carcinoma.

To validate the correlation between ANXA3 expression and prognosis in breast cancer, a retrospective study encompassing 309 breast cancer patients was performed. The expression of ANXA3 was determined by the immunohistochemical examination of tissue sections by the Max Vision™ method. The ANXA3 levels in the patient samples were validated for the prognosis based on age, menopause status, tumor size, tumor node, metastasis stage, the number of lymphatic metastases, oncology grade, and molecular subtyping. An elevated expression of ANXA3 was detected in breast cancer samples, compared to adjacent tissue samples, and significant correlation depending on the number of lymphatic metastases (P = 0.001) and histological grade (P = 0.004) was observed. The number of lymphatic metastases and ANXA3 expression were identified as independent risk factors affecting the disease-free survival and overall survival. Significantly (P < 0.002) higher level of ANXA3 was detected in triple-negative breast cancer compared to other subtypes. There was no significant (P > 0.05) change in the expression of ANXA3 with respect to age, menopausal status, tumor size, and clinical stage. The findings implicate the expression of ANXA3 with the natural progression of breast cancer and associate it with increased lymphatic metastasis. The study validates the use of ANXA3 as a potential prognosis biomarker for breast cancer.