Effects of Contact Surface Shape on Dynamic Lifetime and Strength of Molecular Bond Clusters under Displacement- and Force-Controlled Loading Conditions.

Many experimental and theoretical studies have shown that the mechanical properties of cells and the extracellular matrix can significantly affect the lifetime and strength of the adhesion clusters of molecular bonds. However, there are few studies on how the shape of the contact surface affects the lifetime and strength of the adhesion clusters of molecular bonds, especially theoretical studies in this area. An idealized model of focal adhesion is adopted, in which two rigid media are bonded together by an array of receptor-ligand bonds modeled as Hookean springs on a complex surface topography, which is described by three parameters: the surface shape factor ß, the length of a single identical surface shape L, and the amplitude of surface shapes w. In this study, systematic Monte Carlo simulations of this model are conducted to study the lifetime of the molecular bond cluster under linear incremental force loading and the strength of the molecular bond cluster under linear incremental displacement loading. We find that both small surface shape amplitudes and large surface shape factors will increase the lifetime and strength of the adhesion cluster, whereas the length of a single surface shape causes oscillations in the lifetime and strength of the cluster, and this oscillation amplitude is affected by the surface shape amplitude and the factor. At the same time, we also find that the pretension in the cluster will play a dominant role in the adhesion strength under large amplitudes and small factors of surface shapes. The physical mechanisms behind these phenomena are that the changes of the length of a single surface shape, the amplitude of surface shapes, and the surface shape factor cause the changes of stress concentration in the adhesion region, bond affinity, and the number of similar affinity bonds.

Pachymic acid protects hepatic cells against oxygen-glucose deprivation/reperfusion injury by activating sirtuin 1 to inhibit HMGB1 acetylation and inflammatory signaling.

Ischemia-reperfusion injury is an important cause of liver injury occurring during liver transplantation. It is usually caused by inflammatory response and oxidative stress-induced oxidative damage. Pachymic acid (PA) has various biological activities such as anti-inflammatory, antioxidant and anti-cancer. However, the action mechanism of PA in hepatic ischemia-reperfusion injury is currently unknown. In this study, liver cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to simulate a hepatic ischemia-reperfusion injury model. The binding relationship between PA and sirtuin 1 (SIRT1) was analyzed by molecular docking. Cell viability was detected by Cell Counting Kit-8. Expression levels of SIRT1 and high mobility group box 1 (HMGB1) were detected by western blot. Subsequent levels of inflammatory factors were detected by related kits and western blot. Meanwhile, related kits were used to examine levels of oxidative stress markers including reactive oxygen species, malondialdehyde, superoxide dismutase and cytotoxicity-associated lactate dehydrogenase. Finally, cell apoptosis was detected by flow cytometry and western blot. The results showed that PA significantly ameliorated OGD/R-induced decrease in SIRT1 expression, increase in HMGB1 acetylation and HMGB1 translocation. Moreover, the elevated levels of inflammatory factors, oxidative stress indexes and cell apoptosis upon exposure to OGD/R were reversed by PA treatment. Moreover, the addition of SIRT1 agonist and inhibitor further demonstrated that PA exerted the aforementioned effects in OGD/R-exposed cells by targeting SIRT1. Thus, the present study revealed the mechanism by which PA ameliorated OGD/R-induced hepatic injury via SIRT1. These results might provide a clearer theoretical basis for the targeted treatment of OGD/R-induced hepatic injury with PA.

Effect of Matrix Metalloproteinase 23 Accelerating Wound Healing Induced by Hydroxybutyl Chitosan.

Skin wounds may cause severe financial and social burden due to the difficulties in wound healing. Original inert dressings cannot meet multiple needs in the process of wound healing. Therefore, the development of materials to accelerate healing progress is essential and urgent. In the previous study, we found that the homogeneously synthesized hydroxybutyl chitosan (HBCS) had an effective performance in promoting wound healing. Proteomic analysis of the same specimen suggested that matrix metalloproteinase 23 (MMP23) may play a key role in HBCS expediting the progress of wound healing. In this work, we aim to reveal the underlying mechanism of MMP23 in the dynamic process of cutaneous proliferation and repair period. In order to regulate the expression level of MMP23 in the local wound area, we leaded in adeno-associated virus (AAV) to specifically decreased expression quantity of MMP23 in rat skin. In contrast to the negative control groups, we found that the wound closed faster and the collagen fibers and neovascularization were significantly increased in AAV groups. These findings highlighted that MMP23 was involved in wound healing after traumatic injury, and managing the expression of MMP23 could be a potential intervention target to accelerate wound healing.

MRI-based machine learning model: A potential modality for predicting cognitive dysfunction in patients with type 2 diabetes mellitus.

Background: Type 2 diabetes mellitus (T2DM) is a crucial risk factor for cognitive impairment. Accurate assessment of patients' cognitive function and early intervention is helpful to improve patient's quality of life. At present, neuropsychiatric screening tests is often used to perform this task in clinical practice. However, it may have poor repeatability. Moreover, several studies revealed that machine learning (ML) models can effectively assess cognitive impairment in Alzheimer's disease (AD) patients. We investigated whether we could develop an MRI-based ML model to evaluate the cognitive state of patients with T2DM. Objective: To propose MRI-based ML models and assess their performance to predict cognitive dysfunction in patients with type 2 diabetes mellitus (T2DM). Methods: Fluid Attenuated Inversion Recovery (FLAIR) of magnetic resonance images (MRI) were derived from 122 patients with T2DM. Cognitive function was assessed using the Chinese version of the Montréal Cognitive Assessment Scale-B (MoCA-B). Patients with T2DM were separated into the Dementia (DM) group (n = 40), MCI group (n = 52), and normal cognitive state (N) group (n = 30), according to the MoCA scores. Radiomics features were extracted from MR images with the Radcloud platform. The variance threshold, SelectKBest, and least absolute shrinkage and selection operator (LASSO) were used for the feature selection. Based on the selected features, the ML models were constructed with three classifiers, k-NearestNeighbor (KNN), Support Vector Machine (SVM), and Logistic Regression (LR), and the validation method was used to improve the effectiveness of the model. The area under the receiver operating characteristic curve (ROC) determined the appearance of the classification. The optimal classifier was determined by the principle of maximizing the Youden index. Results: 1,409 features were extracted and reduced to 13 features as the optimal discriminators to build the radiomics model. In the validation set, ROC curves revealed that the LR classifier had the best predictive performance, with an area under the curve (AUC) of 0.831 in DM, 0.883 in MIC, and 0.904 in the N group, compared with the SVM and KNN classifiers. Conclusion: MRI-based ML models have the potential to predict cognitive dysfunction in patients with T2DM. Compared with the SVM and KNN, the LR algorithm showed the best performance.

Circulating tumour cell combined with DNA methylation for early detection of hepatocellular carcinoma.

Background: The inadequate early detection strategies makes hepatocellular carcinoma (HCC) patients with poor prognisis. Therefore, more effective detection methods are urgently needed for early detection and early intervention of HCC. Methods: 17 cases of suspected HCC patients and 11 cases of HBV-related decompensated cirrhosis (HBV-DeCi) patients were enrolled. For each patient, 5 ml blood sample was separated into circulating tumor cells (CTCs) and plasma, CTCs were stained with Diff staining for counting. Plasma was used for extracting cell free DNA (cfDNA) and then analyzed by qMSP assay. Ct values were recorded for GNB4 and Riplet as target genes and ß-actin as an endogenous reference gene. Finally, clinical efficacy of CTC count combined with GNB4/Riplet methylation detection for early diagnosis of HCC was analyzed. Results: The CTC of HCC patients has pleomorphic characteristics, but it is difficult to distinguish from other blood cells with non-obviously pleomorphic of CTC. Although a small number of CTCs can also be detected in HBV-DeCi patients (control group), the number is significantly lower than that in HCC patients, the sensitivity and specificity of CTC for HCC detection were 70.6% and 90.9% (AUC = 0.81). The Ct values of GNB4 and Riplet methylation were significantly different between HCC patients and control group patients. When CTC combined with two genes, the AUC value was significantly increased to 0.98, the sensitivity was 88.2%, and the specificity was 100%. Conclusion: Our study has developed a novel test that CTC count combined with GNB4/Riplet methylation detection and showed its high performance for early diagnosis of HCC.

Identification of CFHR4 associated with poor prognosis of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most leading causes of cancer death worldwide. The 5-year survival rate of HCC patients remains low due to the lack of early-stage symptoms. Human complement factor H-related protein 4 (CFHR4) is a critical gene that belongs to the factor H family of plasma glycoproteins, which has not been linked to HCC development. The correlations between CFHR4 and prognosis and tumor-infiltrating lymphocytes in HCC are yet unknown. The present study demonstrated the involvement of CFHR4 in HCC via data mining approaches. Results: A total of 18 upregulated and 67 down-regulated differentially expressed genes (DEGs) were identified. Importantly, CFHR4, which was screened from DEGs, was shown to express at a lower level in HCC tumor tissue than normal tissues. Western blotting (WB), immunohistochemical (IHC) and quantitative reverse transcription PCR (qRT-PCR) experiments of clinical samples further validated CFHR4 was aberrantly expressed in HCC patients; Data from TCGA showed that CFHR4 was inversely correlated with a cancer family history, histological grade, tumor node metastasis (TNM) stage, and serum AFP level of HCC patients; Univariate and multivariate analyses revealed that low expression of CFHR4 was an independent predictive marker in patients with HCC; Kaplan-Meier analysis showed that the lower expression of CFHR4 was significantly associated with the progression of HCC and poor prognosis rates. Furthermore, TIMER analysis indicated that CFHR4 expression levels had correlations with infiltrating levels of immune cells in HCC. Conclusion: CFHR4 expression was low in HCC and was significantly related to the poor prognosis of HCC and the level of immune infiltration. CFHR4 played important roles in regulating the initiation and progression of HCC and could be a potential biomarker for the diagnosis and prognosis of HCC. Methods: The expression of CFHR4 was analyzed by GEO and TCGA-LIHC database and verified by WB and IHC assay. The biological function of CFHR4 was performed by GO and KEGG enrichment analysis, and the genomic alteration of CFHR4 was investigated by cBioPortal database.The correlation between CFHR4 expression and clinical relevance was evaluated through Cox proportional hazards model, and the correlation between CFHR4 expression and tumor immune infiltrates were studied by TIMER database.

Metformin Regulates Alveolar Macrophage Polarization to Protect Against Acute Lung Injury in Rats Caused by Paraquat Poisoning.

This study explored the role of metformin (MET) in regulating the polarization of alveolar macrophages to protect against acute lung injury (ALI) in rats caused by paraquat (PQ) poisoning. The in vivo studies showed that the 35 mg/kg dose of MET increased the survival rate of rats, alleviated pathological damages to the lungs and their systemic inflammation, promoted the reduction of the pro-inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, and increased the anti-inflammatory factor IL-10 levels in the rat serum. At the same time, the MET intervention decreased the expression of M1 macrophage marker iNOS in the lungs of the PQ-poisoned rats while increasing the M2 macrophage marker, Arg1, expression. In vitro, the concentration of MET > 10 mmol/L affected NR8383 viability adversely and was concentration-dependent; however, no adverse impact on NR8383 viability was observed at MET ≤ 10 mmol/L concentration, resisting the reducing effect of PQ on NR8383 vitality. The PQ-induced NR8383 model with MET intervention showed significantly reduced secretions of IL-6 and TNF-α in NR8383, and lowered expressions of M1 macrophage markers iNOS and CD86. Additionally, MET increased IL-10 secretion and the M2 macrophage markers, Arg1 and Mrcl, expressions. Therefore, we speculate that MET could regulate alveolar macrophage polarization to protect against PQ-poisoning caused ALI.

IL-36γ and IL-36Ra Reciprocally Regulate Colon Inflammation and Tumorigenesis by Modulating the Cell-Matrix Adhesion Network and Wnt Signaling.

Inflammatory bowel disease and colorectal cancer are associated with dysregulation of cytokine networks. However, it is challenging to target cytokines for effective intervention because of the overlapping functions and unpredictable interactions of cytokines in such diverse networks. Here, it is shown that IL-36γ and IL-36Ra, an agonist and an antagonist for IL-36R signaling respectively, reciprocally regulate the experimental colitis and the colon cancer development in mice. Knockout or neutralization of IL-36γ alleviates dextran sulfate sodium (DSS)-induced colitis and inhibits colon cancer development, whereas knockout of IL-36Ra exacerbates DSS-induced colitis and promotes colonic tumorigenesis in multiple colon cancer models in mice. Mechanistically, IL-36γ upregulates extracellular matrix and cell-matrix adhesion molecules and facilitates Wnt signaling, which is mitigated by IL-36Ra or IL-36γ neutralizing antibody. Consistently, IL-36γ levels are positively correlated with extracellular matrix levels and ß-catenin levels in human colorectal tumor biopsies. These findings suggest the critical role of IL-36γ and IL-36Ra in gut inflammation and tumorigenesis and indicate that targeting the IL-36γ/IL-36Ra signal balance provides potential therapeutic strategy for inflammatory bowel disease and gastrointestinal cancers.

Successful Treatment of Severe Toxic Hepatitis and Encephalopathy Without Respiratory Failure Caused by Paraquat Intoxication.

Lung damage is a characteristic feature of paraquat intoxication; most deaths resulting from ingesting paraquat are due to progressive respiratory failure. Liver failure caused by paraquat intoxication is rare. A case of orally ingested paraquat intoxication is reported in which serious liver injury and toxic encephalopathy were observed, but little lung damage was found. The principal systemic symptom was severe liver injury, characterized by cholestasis, that gradually became aggravated. In addition to standard treatment, aggressive treatment through liver protection and cholestasis was administered. Finally, liver function returned to normal and central nervous system symptoms were controlled. The patient was successfully discharged. This case suggests that the hepatotoxicity of paraquat intoxication is possibly characterized by cholestasis, and the treatment of cholestasis promotes recovery of severe hepatocyte damage.

Severity Assessment of COVID-19 Using a CT-Based Radiomics Model.

The coronavirus disease of 2019 (COVID-19) has evolved into a worldwide pandemic. Although CT is sensitive in detecting lesions and assessing their severity, these works mainly depend on radiologists' subjective judgment, which is inefficient in case of a large-scale outbreak. This work focuses on developing a CT-based radiomics model to assess whether COVID-19 patients are in the early, progressive, severe, or absorption stages of the disease. We retrospectively analyzed the CT images of 284 COVID-19 patients. All of the patients were divided into four groups (0-3): early (n = 75), progressive (n = 58), severe (n = 75), and absorption (n = 76) groups, according to the progression of the disease and the CT features. Meanwhile, they were split randomly to training and test datasets with the fixed ratio of 7 : 3 in each category. Thirty-eight radiomic features were nominated from 1688 radiomic features after using select K-best method and the ElasticNet algorithm. On this basis, a support vector machine (SVM) classifier was trained to build this model. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic performance of various models. The precision, recall, and f 1-score of the classification model of macro- and microaverage were 0.82, 0.82, 0.81, 0.81, 0.81, and 0.81 for the training dataset and 0.75, 0.73, 0.73, 0.72, 0.72, and 0.72 for the test dataset. The AUCs for groups 0, 1, 2, and 3 on the training dataset were 0.99, 0.97, 0.96, and 0.93, and the microaverage AUC was 0.97 with a macroaverage AUC of 0.97. On the test dataset, AUCs for each group were 0.97, 0.86, 0.83, and 0.89 and the microaverage AUC was 0.89 with a macroaverage AUC of 0.90. The CT-based radiomics model proved efficacious in assessing the severity of COVID-19.

A novel simple risk model to predict the prognosis of patients with paraquat poisoning.

To identify risk factors and develop a simple model to predict early prognosis of acute paraquat (PQ) poisoning patients, we performed a retrospective cohort study of acute PQ poisoning patients (n = 1199). Patients (n = 913) with PQ poisoning from 2011 to 2018 were randomly divided into training (n = 609) and test (n = 304) samples. Another two independent cohorts were used as validation samples for a different time (n = 207) and site (n = 79). Risk factors were identified using a logistic model with Markov Chain Monte Carlo (MCMC) simulation and further evaluated using a latent class analysis. The prediction score was developed based on the training sample and was evaluated using the testing and validation samples. Eight factors, including age, ingestion volume, creatine kinase-MB [CK-MB], platelet [PLT], white blood cell [WBC], neutrophil counts [N], gamma-glutamyl transferase [GGT], and serum creatinine [Cr] were identified as independent risk indicators of in-hospital death events. The risk model had C statistics of 0.895 (95% CI 0.855-0.928), 0.891 (95% CI 0.848-0.932), and 0.829 (95% CI 0.455-1.000), and predictive ranges of 4.6-98.2%, 2.3-94.9%, and 0-12.5% for the test, validation_time, and validation_site samples, respectively. In the training sample, the risk model classified 18.4%, 59.9%, and 21.7% of patients into the high-, average-, and low-risk groups, with corresponding probabilities of 0.985, 0.365, and 0.03 for in-hospital death events. We developed and evaluated a simple risk model to predict the prognosis of patients with acute PQ poisoning. This risk scoring system could be helpful for identifying high-risk patients and reducing mortality due to PQ poisoning.

Pharmacokinetics and bioavailability of solid dispersion formulation of tilmicosin in pigs.

Tilmicosin (TMS) is a semisynthetic macrolide antibiotic restricted to veterinary use but is only partially soluble in aqueous solutions, which limits its administration in treatments. We developed a strategy to enhance the supersaturated solubility of TMS using amorphous solid dispersion (SD). The dissolution profile shown that the dissolution rate of TMS-SD was obviously faster than TMS. The pharmacokinetics of tilmicosin (TMS) and tilmicosin solid dispersion (TMS-SD) in pigs after oral administration at a single dose of 50 mg/kg b.w were investigated. The tmax of TMS-SD (2.50 hr) was 1.80 times faster than TMS (4.50 hr) (p < .05). There were no significant differences in the other PK parameters (Cmax , t1/2ß , V/F, CL/F, MRT, and AUC0-inf ) (p > .05). The mean relative bioavailability of TMS-SD compared with TMS was 140.39%, according to the AUC0-inf values. These results demonstrated that the solid dispersion technique enhanced the bioavailability of TMS and the new formulation administered to animals via drinking water may be used as a therapeutic alternative for clinical treatments.

Octreotide alleviates pancreatic damage caused by paraquat in rats by reducing inflammatory responses and oxidative stress.

This study explores the efficacy and mechanism by which octreotide (OCT) alleviates paraquat (PQ)-induced pancreatic injury. Twenty-four adult male rats were randomly divided into three groups: the normal control (NC), PQ poisoning, and OCT treatment groups. The PQ-induced pancreatic injury rat model was established by administering PQ (120 mg/kg). Treatment group rats received OCT (8 µg/kg body weight) every 8 h by subcutaneous injection, 1 h after PQ administration. Rats were euthanized 24 h after PQ injection. Serum amylase, lipase, tumor necrosis factor-α, and interleukin-6 levels were markedly increased in the PQ group versus the NC group. In pancreatic tissue, PQ poisoning drastically induced necrosis and increased inflammatory cytokine and oxidative stress marker levels. Compared with the PQ group, OCT reduced pancreatic damage and histological scores, serum amylase, lipase, and inflammatory cytokine levels, as well as oxidative stress. OCT demonstrates protective effects against PQ-induced pancreatic damage through anti-inflammatory and antioxidant actions.

As(III) removal from aqueous solution by katoite (Ca3Al2(OH)12).

As (III) is widely distributed in groundwater which is relatively harder to be removed comparing to As (V). Co-grinding Ca(OH)2 with Al(OH)3 was conducted to manufacture katoite (Ca3Al2(OH)12) for the complete removal of As(III) (concentration below drinking water standard of WHO (<10 ppb)) during one-step agitation operation. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TG), and X-ray photoelectron spectroscopy (XPS) were applied for the illustration of adsorption mechanism. Katoite could intercalate As(III) into the layered space forming arsenite pillared Ca-Al layered double hydroxide (LDH). The coexisting anions such as Cl-, SO42-, and NO3- had minor effects on As (III) removal performance using katoite. Techno-economic analysis demonstrated the feasibility of large-scale katoite production and its practical application for As(III) polluted groundwater purification, especially in the undeveloped areas where groundwater was used as irrigation and drinking water.

Muir-Torre Syndrome With a Frame-shift Mutation in the MSH2 Gene: A Rare Case Report and Literature Review.

Muir-Torre syndrome is a rare subtype of Lynch syndrome characterized by coincidence of skin neoplasm and visceral malignancies. Here, we report a case of this rare disease, whose diagnosis of the syndrome was first suspected by the pathologist. This was a 60-yr-old woman who presented with an axillary skin nodule, which was diagnosed as basal cell carcinoma. Further inquiry revealed that she was hospitalized for evaluation of a recurrent vaginal stump endometrial carcinoma. Histologic workup and immunohistochemistry for mismatch repair proteins of both the skin and vaginal tumor suggested the possibility of Muir-Torre syndrome. NexGen sequencing identified a frame-shift mutation in the MSH2 gene. The patient was found to have a metachronous colorectal carcinoma, uterine endometrial carcinoma, and skin cancer from 1998 to 2016. Five family members had also suffered from colorectal cancer or glioma. This case report illustrates the importance of the multidisciplinary care approach, mismatch repair protein and gene testing, and detailed medical history taking into consideration the diagnosis of Muir-Torre syndrome.

The deubiquitinase USP25 supports colonic inflammation and bacterial infection and promotes colorectal cancer.

Bacterial infection or abnormal colonization in the gastrointestinal system is associated with subsets of inflammatory bowel disease and colorectal cancer. Here we demonstrated essential roles of ubiquitin-specific protease 25 (USP25) in experimental colitis, bacterial infections and colon cancer. Knockout or pharmacologic inhibition of USP25 potentiated immune responses after induction of experimental colitis or bacterial infections that promoted clearance of infected bacteria and resolution of inflammation and attenuated Wnt and SOCS3-pSTAT3 signaling, which inhibited colonic tumorigenesis. USP25 levels were positively or negatively correlated with Fusobacterium nucleatum colonization and ß-catenin levels or SOCS3 levels in human colorectal tumor biopsies, respectively, and predicted poor prognosis of patients with cancers in the gastrointestinal system. Our findings suggest USP25 as a promoter and druggable target for gastrointestinal infections and cancers.

Mechanochemical approach to synthesize citric acid-soluble fertilizer of dittmarite (NH4MgPO4·H2O) from talc/NH4H2PO4 mixture.

In this study, a citric acid-soluble fertilizer of dittmarite (NH4MgPO4·H2O) was synthesized by balling talc with NH4H2PO4. The effects of ball milling speed and milling time on the dissolution rates of N, P and Mg in deionized water and 2% citric acid were explored. Characterization technologies such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TG) and Scanning electron microscopy (SEM) were applied to test the prepared samples. In water, the prepared dittmarite was changed into struvite (NH4MgPO4·6H2O) with almost no N, P or Mg release, while the dissolution rates of nutrient elements reached almost 100% in 2% citric acid. The proposed work presented a facile and environmentally friendly method to produce CASF with high agricultural and ecological value.

Isolation and characterization of spontaneously immortalized B-lymphocyte lines from HIV-infected patients with and without non-Hodgkin's Lymphoma.

Isolation of viable circulating tumor cells (CTC) holds the promise for improving screening, early diagnosis, and personalized treatment of lymphoma. In this study, we isolated and characterized spontaneously immortalized B-lymphocyte (SIBC) lines from HIV-infected patients with and without Non-Hodgkin's Lymphoma (AIDS-NHL). A total of 22 SIBC lines was isolated from peripheral blood mononuclear cells (PBMC) of HIV-infected patients with (n = 40) and without (n = 77) clinically detectable NHL, but not from healthy individuals (n = 34). Of these, 8 SIBC lines named HIV-SIBC were generated from HIV-infected patients without AIDS-NHL (10%, 8/77), while 14 SIBCs named AIDS-NHL-SIBC were from 13 of the AIDS-NHL patients (32.5%, 13/40). Among the 14 AIDS-NHL-SIBCs, 12 were derived from AIDS-NHL patients with poor prognoses (survival time less than 1 year). SIBCs displayed markers typical of memory B cells (CD3- CD20+ CD27+ ) with EBV infection. Moreover, AIDS-NHL-SIBCs were representative of CTC as evidenced by monoclonal Ig gene rearrangement, abnormal chromosomal karyotype, and the formation of xenograft tumors, while HIV-SIBCs generated harbored some features of tumor cells, none had the capacity of xenograft tumor formation, suggesting HIV-SIBC present the precursor of CTC. These results indicate that SIBCs is associated with poor prognosis in AIDS-NHL patients and can be isolated from HIV-infected patients with NHL and without NHL. This findings point to the need for further molecular characterization and functional studies of SIBCs, which may prove the value of SIBCs in the diagnosis, prognoses, and screening for NHL among HIV-infected patients.

The effect of an alternative chromosome 17 probe on fluorescence in situ hybridization for the assessment of HER2 amplification in invasive breast cancer.

Fluorescent in situ hybridization (FISH) is commonly used to determine the ratio of human epidermal growth factor receptor 2 (HER2) to centromere enumeration probe for chromosome 17 (CEP17), which further determines HER2 gene status in breast cancer. However, due to copy number alteration in CEP17, inaccurate diagnoses can occur. The current study was performed to investigate the diagnostic value of an alternative CEP17 reference probe for HER2 status in invasive breast cancer. A higher-order repeat in the centromeric region of chromosome 17 was identified and an alternative probe (SCEP17) was subsequently prepared. Karyotype analysis of peripheral blood was used to detect SCEP17 probe specificity. Using a HER2/CEP17 probe, karyotype analysis revealed two strong green signals at the centromere of chromosome 17 and one weaker signal at the other centromere. However, two strong hybridization signals at the centromere of chromosome 17 were observed when the HER2/SCEP17 probe was used. In the 425 patients with invasive breast cancer, no statistical difference was observed between HER2/SCEP17 and HER2/CEP17 when detecting HER2 gene amplification (P=0.157). However, in terms of copy number, the SCEP17 probe exhibited a reduced number compared with the conventional CEP17 probe (P<0.001). In conclusion, the HER2/SCEP17 probe may lead to increased accuracy HER2 status assessment in invasive breast cancer. However, a further large-scale and prospective clinical trial is required for confirmation of the potential benefits of using the HER2/SCEP17 probe.