Combined analysis of estradiol and ß-hCG to predict the early pregnancy outcome of FET: a retrospective study.

BACKGROUND: The accurate prediction of pregnancy outcomes in in vitro fertilization (IVF) cycles is crucial. While several studies have been conducted on the predictive power of serum estradiol (E2) and ß-hCG concentrations post-embryo transfer (ET) for pregnancy outcomes, there is debate on the predictive value of E2. The objective of this study was to investigate the predictive efficacy of combining serum E2 and ß-hCG levels on early reproductive outcomes 12 days after embryo transfer. METHODS: A total of 1521 patients with ß-hCG positive values on day 12 following frozen-thawed embryo transfer (FET) with natural endometrial preparation cycles (NCs) were gathered in affiliated Women's Hospital of Jiangnan University. Using logistic regression, the relationship between pregnancy outcome and early serum E2 and ß-hCG concentrations was examined. The receiver-operating characteristic (ROC) analysis was used to assess the predictive accuracy of the serum E2 and ß-hCG concentrations. RESULTS: Notable distinctions were observed in the serum E2 and ß-hCG levels on the twelfth day following FET with NCs between the groups classified as clinical pregnancy group (CP Group) and biochemical pregnancy group (BP Group). In addition, the cutoff values for E2 and ß-hCG on day 12 following FET with NCs in cleavage embryo group (CE Group) were 129.25 pg/mL and 156.60 mIU/mL, respectively. The threshold values for E2 and ß-hCG for the blastocyst group (B Group) were 174.45 pg/mL and 217.70 mIU/mL. Serum E2 day12 and ß-hCG day12 were found to be substantially linked with clinical pregnancy by logistic regression analysis. CONCLUSIONS: Serum E2 and ß-hCG concentrations were found to be significantly different between the CP Group and BP Group in infertility women underwent FET with NCs. Our retrospective cohort study's findings suggest that the combination of early E2 and ß-hCG levels on day 12 post-FET could be used as a predictive tool to evaluate the likelihood of both positive and negative pregnancy outcomes in FET with NCs.

Qingzhuan dark tea polysaccharides-zinc alleviates dextran sodium sulfate-induced ulcerative colitis.

BACKGROUND: Qingzhuan dark tea polysaccharides (QDTP) have been complexed with Zinc (Zn) to form the Qingzhuan dark tea polysaccharides-Zinc (QDTP-Zn) complex. The present study investigated the protective effects of QDTP-Zn on ulcerative colitis (UC) in mice. The UC mouse model was induced using dextran sodium sulfate (DSS), followed by oral administration of QDTP-Zn (0.2 and 0.4 g kg-1 day-1). RESULTS: QDTP-Zn demonstrated alleviation of UC symptoms in mice, as evidenced by a decrease in disease activity index scores. QDTP-Zn also regulated colon tissue injury by upregulating ZO-1 and occludin protein expression, at the same time as downregulating tumor necrosis factor-α and interleukin-6ß levels. Furthermore, QDTP-Zn induced significant alterations in the abundance of bacteroidetes and firmicutes and notably increased levels of short-chain fatty acids (SCFAs), particularly acetic acid, propionic acid, and butyric acid. CONCLUSION: In summary, QDTP-Zn exhibits therapeutic potential in alleviating enteritis by fortifying the colonic mucosal barrier, mitigating inflammation and modulating intestinal microbiota and SCFAs levels. Thus, QDTP-Zn holds promise as a functional food for both the prevention and treatment of UC. © 2024 Society of Chemical Industry.

Low-dose hypomethylating agents cooperate with ferroptosis inducers to enhance ferroptosis by regulating the DNA methylation-mediated MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway in acute myeloid leukemia.

BACKGROUND: Ferroptosis is a new form of nonapoptotic and iron-dependent type of cell death. Glutathione peroxidase-4 (GPX4) plays an essential role in anti-ferroptosis by reducing lipid peroxidation. Although acute myeloid leukemia (AML) cells, especially relapsed and refractory (R/R)-AML, present high GPX4 levels and enzyme activities, pharmacological inhibition of GPX4 alone has limited application in AML. Thus, whether inhibition of GPX4 combined with other therapeutic reagents has effective application in AML is largely unknown. METHODS: Lipid reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) assays were used to assess ferroptosis in AML cells treated with the hypomethylating agent (HMA) decitabine (DAC), ferroptosis-inducer (FIN) RAS-selective lethal 3 (RSL3), or their combination. Combination index (CI) analysis was used to assess the synergistic activity of DAC + RSL3 against AML cells. Finally, we evaluated the synergistic activity of DAC + RSL3 in murine AML and a human R/R-AML-xenografted NSG model in vivo. RESULTS: We first assessed GPX4 expression and found that GPX4 levels were higher in AML cells, especially those with MLL rearrangements, than in NCs. Knockdown of GPX4 by shRNA and indirect inhibition of GPX4 enzyme activity by RSL3 robustly induced ferroptosis in AML cells. To reduce the dose of RSL3 and avoid side effects, low doses of DAC (0.5 µM) and RSL3 (0.05 µM) synergistically facilitate ferroptosis by inhibiting the AMP-activated protein kinase (AMPK)-SLC7A11-GPX4 axis. Knockdown of AMPK by shRNA enhanced ferroptosis, and overexpression of SLC7A11 and GPX4 rescued DAC + RSL3-induced anti-leukemogenesis. Mechanistically, DAC increased the expression of MAGEA6 by reducing MAGEA6 promoter hypermethylation. Overexpression of MAGEA6 induced the degradation of AMPK, suggesting that DAC inhibits the AMPK-SLC7A11-GPX4 axis by increasing MAGEA6 expression. In addition, DAC + RSL3 synergistically reduced leukemic burden and extended overall survival compared with either DAC or RSL3 treatment in the MLL-AF9-transformed murine model. Finally, DAC + RSL3 synergistically reduced viability in untreated and R/R-AML cells and extended overall survival in two R/R-AML-xenografted NSG mouse models. CONCLUSIONS: Our study first identify vulnerability to ferroptosis by regulating MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway. Combined treatment with HMAs and FINs provides a potential therapeutic choice for AML patients, especially for R/R-AML.

Investigation of polysaccharide from Radix Aconiti Lateralis Preparata (Fuzi) cardio protective effect on doxorubicin-induced chronic cardiotoxicity.

OBJECTIVES: Doxorubicin (DOX) is a chemotherapy drug for treating malignant tumours. However, its cardiotoxicity has limited its clinical application. The Radix Aconiti Lateralis Preparata, also known as Fuzi, has been used for treating heart failure. Nevertheless, there is still a deficiency of claeity as to whether the Fuzi polysaccharide (FPS) may prevent the side effects of DOX. METHODS: Mice were intraperitoneally administered DOX (15 mg/kg) to establish a mouse model of DOX-induced chronic cardiotoxicity (DICC). The mice were then administered different doses of FPS or enalapril intragastrically. KEY FINDINGS: In the DOX group, the activity of CK-MB and LDH and the content of NT-proBNP in serum of mice were increased. Myocardial infiltration of inflammatory cells and cytoplasmic vacuolation occurred. Levels of NLRP3, ASC, Caspase-1, IL-1ß, IL-18, IL-6, and Bax increased, whereas levels of Bcl-2, STAT3, and p-STAT3 decreased. After administering FPS (100 mg/kg and 200 mg/kg), there were reductions in CK-MB activity and NT-proBNP levels. Cytoplasmic vacuolation, interstitial infiltration of blood, and infiltration of inflammatory cells were alleviated. The changes in protein expression mentioned above were reversed. CONCLUSIONS: FPS can protect heart function and structure in DICC mice by inhibiting NLRP3 inflammasome-mediated pyroptosis and IL-6/STAT3 pathway-induced apoptosis.

Role of adhesion molecules in cancer and targeted therapy.

Adhesion molecules mediate cell-to-cell and cell-to-extracellular matrix interactions and transmit mechanical and chemical signals among them. Various mechanisms deregulate adhesion molecules in cancer, enabling tumor cells to proliferate without restraint, invade through tissue boundaries, escape from immune surveillance, and survive in the tumor microenvironment. Recent studies have revealed that adhesion molecules also drive angiogenesis, reshape metabolism, and are involved in stem cell self-renewal. In this review, we summarize the functions and mechanisms of adhesion molecules in cancer and the tumor microenvironment, as well as the therapeutic strategies targeting adhesion molecules. These studies have implications for furthering our understanding of adhesion molecules in cancer and providing a paradigm for exploring novel therapeutic approaches.

Antimicrobial Activity of Stilbenes from Bletilla striata against Cutibacterium acnes and Its Effect on Cell Membrane.

The abnormal proliferation of Cutibacterium acnes is the main cause of acne vulgaris. Natural antibacterial plant extracts have gained great interest due to the efficacy and safety of their use in skin care products. Bletilla striata is a common externally used traditional Chinese medicine, and several of its isolated stilbenes were reported to exhibit good antibacterial activity. In this study, the antimicrobial activity of stilbenes from B. striata (BSS) against C. acnes and its potential effect on cell membrane were elucidated by determining the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), bacterial growth curve, adenosine triphosphate (ATP) levels, membrane potential (MP), and the expression of genes related to fatty acid biosynthesis in the cell membrane. In addition, the morphological changes in C. acnes by BSS were observed using transmission electron microscopy (TEM). Experimentally, we verified that BSS possessed significant antibacterial activity against C. acnes, with an MIC and MBC of 15.62 µg/mL and 62.5 µg/mL, respectively. The growth curve indicated that BSS at 2 MIC, MIC, 1/2 MIC, and 1/4 MIC concentrations inhibited the growth of C. acnes. TEM images demonstrated that BSS at an MIC concentration disrupted the morphological structure and cell membrane in C. acnes. Furthermore, the BSS at the 2 MIC, MIC, and 1/2 MIC concentrations caused a decrease in the intracellular ATP levels and the depolarization of the cell membrane as well as BSS at an MIC concentration inhibited the expression of fatty acid biosynthesis-associated genes. In conclusion, BSS could exert good antimicrobial activity by interfering with cell membrane in C. acnes, which have the potential to be developed as a natural antiacne additive.

Oncoplastic breast-conserving surgery improves cosmetic outcomes without increasing recurrence risk compared to modified radical mastectomy in early breast cancer patients: development and validation of a recurrence risk prediction model.

In the quest for effective treatment of early-stage breast cancer, this study aimed to compare the clinical efficacy of modified radical mastectomy (MRM) and oncoplastic breast-conserving surgery (OBCS). Breast cancer remains a major health concern globally, where early detection and effective treatment strategies are crucial for improving the outcomes of patients. MRM and OBCS are two primary treatment modalities for breast cancer, each with its distinct benefits and challenges. Through a retrospective analysis, we found that although the patients in the OBCS group experienced a longer operation time, they had significantly less intraoperative bleeding, postoperative drainage, and hospitalization time compared to the MRM group. Furthermore, patients in the OBCS group demonstrated higher subjective satisfaction and quality of life scores, along with better objective outcomes. In terms of postoperative complications and recurrence rates, no significant difference was identified between the two groups. However, our multivariate Cox regression analysis identified lymph node metastasis and molecular type as independent prognostic factors for disease-free survival (DFS). Subsequently, we constructed a risk model based on these variables, which was proven to be effective in predicting recurrence, with an area under the risk score curve for recurrence prediction being 0.852. The group with a lower risk score demonstrated a significantly higher DFS rate. Our study suggests that compared with MRM, OBCS can significantly reduce surgical incision, improve patient satisfaction, and does not increase the risk of complications or recurrence. Our risk model, developed using Cox regression, also demonstrated high clinical value in predicting breast cancer recurrence, thereby aiding in personalized patient management and treatment planning.

Galangin: A food-derived flavonoid with therapeutic potential against a wide spectrum of diseases.

Galangin is an important flavonoid with natural activity, that is abundant in galangal and propolis. Currently, various biological activities of galangin have been disclosed, including anti-inflammation, antibacterial effect, anti-oxidative stress and aging, anti-fibrosis, and antihypertensive effect. Based on the above bioactivities, more and more attention has been paid to the role of galangin in neurodegenerative diseases, rheumatoid arthritis, osteoarthritis, osteoporosis, skin diseases, and cancer. In this paper, the natural sources, pharmacokinetics, bioactivities, and therapeutic potential of galangin against various diseases were systematically reviewed by collecting and summarizing relevant literature. In addition, the molecular mechanism and new preparation of galangin in the treatment of related diseases are also discussed, to broaden the application prospect and provide reference for its clinical application. Furthermore, it should be noted that current toxicity and clinical studies of galangin are insufficient, and more evidence is needed to support its possibility as a functional food.

Efficacy of Invariant Natural Killer T Cell Infusion Plus Transarterial Embolization vs Transarterial Embolization Alone for Hepatocellular Carcinoma Patients: A Phase 2 Randomized Clinical Trial.

Purpose: Invariant NKT cells (iNKT) are CD1d-restricted T cells with the capacity of antitumor immunity. The safety of autologous iNKT cell treatment in hepatocellular carcinoma (HCC) has been verified. This study aimed to investigate its efficacy in advanced HCC after transarterial chemoembolization (TACE) failure. Patients and methods: This open-label, randomized, controlled, trial enrolled 60 patients with unresectable HCC after TACE failure at three centers. Transarterial embolization (TAE) was used instead of TACE to protect iNKT cell function. Patients were randomly assigned (1:1) to receive TAE therapy with (TAE-iNKT) or without (TAE) biweekly iNKT cell infusion. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), peripheral blood cell count, and safety. Results: Fifty-four patients completed the study. Median PFS was significantly higher in TAE-iNKT patients (5.7 months [95% CI, 4.3-7.0 months]) compared with TAE patients (2.7 months [95% CI, 2.3-3.2 months]; hazard ratio 0.32 [95% CI, 0.16-0.63]; P<0.001). Higher ORR and DCR were observed in TAE-iNKT patients (52% and 85%, respectively) compared with TAE patients (11% and 33%; respectively). Five TAE-iNKT patients and 1 TAE patient achieved completed response. The median time to deterioration in QoL was longer in TAE-iNKT patients (9.2 months [95% CI, 6.0-13.3 months]) compared with TAE patients (3.0 months [95% CI, 2.9-3.0 months]). The mean lymphocytes were higher in the TAE-iNKT group than in the TAE group at 8 (1.48 vs 0.95×109/L, P = 0.007) and 12 (1.49 vs 0.89×109/L, P = 0.001) weeks. Grade 3 adverse events occurred in 1 TAE-iNKT patient (4%) and 5 TAE patients (19%). All the other adverse events were grade 1-2. Conclusion: iNKT cell infusion significantly improved PFS, ORR, DCR, and QoL with manageable toxicity during TAE therapy in patients with HCC. Trial Registration ClinicalTrials.gov Identifier: NCT04011033.

[Associations Between Insulin Resistance Indexes and Hyperuricemia in Hypertensive Population].

Objective To explore the relationship between insulin resistance (IR) indexes and hyperuricemia (HUA) among the people with hypertension. Methods From July to August in 2018,hypertension screening was carried out in Wuyuan county,Jiangxi province,and the data were collected through questionnaire survey,physical measurement,and biochemical test.Logistic regression was performed to analyze the relationship between HUA and IR indexes including metabolic score for IR (METS-IR),triglyceride-glucose (TyG) index,TyG-body mass index (BMI),TyG-waist circumference (WC),visceral adiposity index (VAI),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and lipid accumulation product (LAP).The penalty spline method was used for the curve fitting between IR indexes and HUA.The area under the receiver operating characteristic curve (AUC) was employed to reveal the correlation between each index and HUA. Results The 14 220 hypertension patients included 6 713 males and 7 507 females,with the average age of (63.8±9.4) years old,the average uric acid level of (418.9±120.6) mmol/L,and the HUA detection rate of 44.4%.The HUA group had higher proportions of males,current drinking,current smoking,diabetes,and using antihypertensive drugs,older age,higher diastolic blood pressure,WC,BMI,homocysteine,total cholesterol,TG,low-density lipoprotein cholesterol,blood urea nitrogen,creatinine,aspartate aminotransferase,alanine aminotransferase,total protein,albumin,total bilirubin,direct bilirubin, METS-IR, TyG, TyG-BMI, TyG-WC, VAI, TG/HDL-C, and LAP, and lower systolic blood pressure and HDL-C than the normal uric acid group (all P<0.05).Multivariate Logistic regression showed that METS-IR (OR=1.049,95%CI=1.038-1.060, P<0.001), TyG (OR=1.639,95%CI=1.496-1.797, P<0.001), TyG-BMI (OR=1.008,95%CI=1.006-1.010, P<0.001), TyG-WC (OR=1.003,95%CI=1.002-1.004, P<0.001), lnVAI (OR=1.850, 95%CI=1.735-1.973, P<0.001), ln(TG/HDL-C) (OR=1.862,95%CI=1.692-2.048, P<0.001),and lnLAP (OR=1.503,95%CI=1.401-1.613,P<0.001) were associated with the risk of HUA.Curve fitting indicated that METS-IR,TyG,TYG-BMI,TYG-WC,lnVAI,ln(TG/HDL-C),and lnLAP were positively correlated with HUA (all P<0.001),and the AUC of TyG index was higher than that of other IR indexes (all P<0.05). Conclusion Increased IR indexes,especially TyG,were associated with the risk of HUA among people with hypertension.

Bioactive compounds and mechanism of Xianglian pill in the treatment of gastric cancer: Network pharmacology analysis and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastric cancer (GC) affects people's quality of life because of its high incidence rate and mortality. The Xianglian Pill (XLP) is a traditional Chinese medicine (TCM) prescription used to treat gastrointestinal (GI） diseases. Its anti-tumor effect has been found in recent years, but it's bioactive compounds and mechanism of action in treating GC are remain unknown. AIM OF THE STUDY: This study reveals the bioactive compounds and mechanisms of XLP in the treatment of GC through network pharmacology analysis and experimental verification. MATERIALS AND METHODS: The main compounds in XLP were searched and the active compounds with anti-GC activity were selected. Compounds targets and GC- related targets were predicted, and common targets were obtained. Subsequently, a protein-protein interaction (PPI) network of common targets is constructed, while GO and KEGG enrichment analyses were performed on common targets. Finally, the anti-GC effects of active compounds in XLP were verified in GC cell lines MGC-803 and HGC-27 by wound healing assay, cell cycle assay, cell apoptosis assay and western blotting (WB) assay. RESULTS: A total of 33 active compounds of XLP were obtained. MTT assay showed that dehydrocostus lactone (DHL) and berberrubine (BRB) had lower IC50 value in GC cells HGC-27 and MGC-803, and has a less inhibitory effect on normal gastric epithelial cells. Further, 73 common targets were obtained after the total target of DHL and BRB intersected with GC. Among them, CASP3, AKT1, SRC, STAT3,and CASP9 were the most associated genes in the PPI network. GO and KEGG enrichment analyses indicated that apoptosis played a major role in the biological processes and signaling pathways involved. Moreover, the in vitro experiment revealed that DHL and BRB inhibited GC cell viability via inducing cell cycle arrest at G2/M phase, and promoting cell apoptosis by up-regulating the caspase3 expression and down-regulating the expression of Bcl2/Bax. CONCLUSIONS: DHL and BRB are the two main anti-GC active compounds in XLP, and their mechanism is mainly to inhibit cell cycle and promote cell apoptosis.

DNA hypermethylation-induced miR-182 silence targets BCL2 and HOXA9 to facilitate the self-renewal of leukemia stem cell, accelerate acute myeloid leukemia progression, and determine the sensitivity of BCL2 inhibitor venetoclax.

Rationale: microRNAs (miRNAs) are frequently deregulated and play important roles in the pathogenesis and progression of acute myeloid leukemia (AML). miR-182 functions as an onco-miRNA or tumor suppressor miRNA in the context of different cancers. However, whether miR-182 affects the self-renewal of leukemia stem cells (LSCs) and normal hematopoietic stem progenitor cells (HSPCs) is unknown. Methods: Bisulfite sequencing was used to analyze the methylation status at pri-miR-182 promoter. Lineage-negative HSPCs were isolated from miR-182 knockout (182KO) and wild-type (182WT) mice to construct MLL-AF9-transformed AML model. The effects of miR-182 depletion on the overall survival and function of LSC were analyzed in this mouse model in vivo. Results: miR-182-5p (miR-182) expression was lower in AML blasts than normal controls (NCs) with hypermethylation observed at putative pri-miR-182 promoter in AML blasts but unmethylation in NCs. Overexpression of miR-182 inhibited proliferation, reduced colony formation, and induced apoptosis in leukemic cells. In addition, depletion of miR-182 accelerated the development and shortened the overall survival (OS) in MLL-AF9-transformed murine AML through increasing LSC frequency and self-renewal ability. Consistently, overexpression of miR-182 attenuated AML development and extended the OS in the murine AML model. Most importantly, miR-182 was likely dispensable for normal hematopoiesis. Mechanistically, we identified BCL2 and HOXA9 as two key targets of miR-182 in this context. Most importantly, AML patients with miR-182 unmethylation had high expression of miR-182 followed by low protein expression of BCL2 and resistance to BCL2 inhibitor venetoclax (Ven) in vitro. Conclusions: Our results suggest that miR-182 is a potential therapeutic target for AML patients through attenuating the self-renewal of LSC but not HSPC. miR-182 promoter methylation could determine the sensitivity of Ven treatment and provide a potential biomarker for it.

Immune checkpoint blockade PD-1 therapy for primary liver cancer: incidence and influencing factors of thyroid dysfunction.

OBJECTIVES: To investigate the incidence and influencing factors of thyroid dysfunction (TD) in patients with primary liver cancer (PLC) induced by PD-1 monoclonal antibodies. METHODS: Clinical data were collected from 195 PLC patients treated with PD-1. They were divided into TD group and normal thyroid function (NTF) group, and further divided into TD subgroups, the differences between groups and subgroups were analyzed. RESULTS: A total of 113 of 195 (57.9%) PLC patients developed TD. The positive rate of thyroid antibody (20.6% vs. 0%, P = 0.041) and the median value of TSH (6.20 vs. 2.16 mU/L, P = 0.000) in TD group were higher than those in NTF group. Ten patients (8.8%) had the CTCAE grade of TD above grade 3, of which 2 patients died of liver failure. There were 20 patients (17.7%) in hyperthyroidism group and 93 patients (82.3%) in hypothyroidism group. The decompensated cirrhosis in hyperthyroidism group was lower than that in hypothyroidism group (33.3% vs. 65.6%, P = 0.010), and the proportion of patients who had previously received surgical treatment was higher than that in hypothyroidism group (35.0% vs. 9.7%, P = 0.003); The proportion of clinical hyperthyroidism was higher than that of clinical hypothyroidism (70.0% vs. 31.2%, P = 0.001), the proportion of decompensated liver cirrhosis in clinical hyperthyroidism group was lower than that in clinical hypothyroidism group (23.1% vs. 68.0%, P = 0.022), and the proportion of previous or combined surgical resection was much higher than that in clinical hypothyroidism group (42.9% vs. 7.1%, P = 0.018); The proportion of decompensated cirrhosis in primary TD group was lower than that in secondary TD group (36.5% vs. 83.3%, P = 0.002), and the proportion of patients using antitumor targeted drugs was higher than that in secondary TD group (73.1% vs. 45.0%, P = 0.014). CONCLUSION: Patients with PLC had high incidence of TD after receiving PD-1 treatment, primary or subclinical hypothyroidism was the main manifestation type, which was related to the degree of disease and treatment.

Evaluation of indocyanine green combined with methylene blue staining in sentinel lymph node biopsy of breast cancer.

Background: Methylene blue as tracer used in sentinel lymph node biopsy (SLNB) have low detection rate and high false negative rate. Indocyanine green (ICG) can detect the flow of subcutaneous lymphatic vessels and the position of lymph nodes dynamically. This study sought to evaluate the efficacy of ICG combined with methylene blue staining in SLNB of breast cancer. Methods: One hundred and fifty-six early breast cancer patients treated at our hospital from July 2020 to May 2022 were enrolled in this study. SLNB was performed by ICG combined with methylene blue staining under the guidance of the fluorescent tracer navigation system FLI-10B. Standard axillary lymph node dissection (ALND) was performed in patients with sentinel lymph node (SLN) metastasis confirmed by intraoperative frozen pathology, while low ALND was performed in patients with negative SLNs. According to the staining condition, the SLNs were divided into: (I) the combined group (SLNs with methylene blue staining and/or ICG luminescence); (II) the methylene blue group (SLNs with methylene blue staining alone); and (III) the ICG group (SLNs with ICG luminescence alone). The detection rate, accuracy, sensitivity, and false negative rate of SLNB were compared among the 3 groups. Results: A total of 592 SLNs were detected in the combined group (average 3.8 SLNs), yielding a detection rate of 97.4%; the accuracy, sensitivity, and false negative rates were 97.4%, 92.7%, and 7.3%. In the methylene blue group, 390 SLNs were detected (average 2.5 SLNs), yielding a detection rate of 84.6%; the accuracy, sensitivity, and false negative rates were 83.3%, 89.1%, and 10.9%. A total of 483 SLNs were detected in the ICG group (average 3.1 SLNs), the detection rate was 92.9%; the accuracy, sensitivity and false negative rates were 91.7%, 90.9%, and 9.1%. The average number of detected SLNs, detection rate and accuracy rate in the combined group were higher than those in the methylene blue group (P<0.05), and the accuracy rate of the combined group was higher than that of the ICG group (P<0.05). Conclusions: ICG combined with methylene blue staining is a promising and effective tracing strategy in the SLNB of breast cancer with high detection and accuracy rates.

Construction of a lncRNA-mRNA Co-Expression Network for Nasopharyngeal Carcinoma.

Long non-coding RNAs (lncRNAs) widely regulate gene expression and play important roles in the pathogenesis of human diseases, including malignant tumors. However, the functions of most lncRNAs remain to be elucidated. In order to study and screen novel lncRNAs with important functions in the carcinogenesis of nasopharyngeal carcinoma (NPC), we constructed a lncRNA expression profile of 10 NPC tissues and 6 controls through a gene microarray. We identified 1,276 lncRNAs, of which most are unknown, with different expression levels in the healthy and NPC tissues. In order to shed light on the functions of these unknown lncRNAs, we first constructed a co-expression network of lncRNAs and mRNAs using bioinformatics and systematic biological approach. Moreover, mRNAs were clustered and enriched by their biological functions, and those lncRNAs have similar expression trends with mRNAs were defined as functional molecules with potential biological significance. The module may help identify key lncRNAs in the carcinogenesis of NPC and provide clues for in-depth study of their functions and associated signaling pathways. We suggest the newly identified lncRNAs may have clinic value as biomarkers and therapeutic targets for NPC diagnosis and treatment.

Internet+Continuous Nursing Mode in Home Nursing of Patients with T-Tube after Hepatolithiasis Surgery.

This study was to explore the effect of a continuous nursing model based on the mobile Internet in the home nursing of patients with T-tube after hepatolithiasis surgery. A continuous nursing system based on the mobile Internet was constructed, and 94 discharged patients with T-tube after biliary tract surgery were selected as the study subjects. The differences of complication rate, referral rate, nursing satisfaction, self-care ability, and quality of life score through the 36-item short form health survey (SF-36) after routine health education nursing (control group, n = 47) and continuous nursing mode based on the Internet (observation group, n = 47) were explored. The results showed that the success rate of the continuous nursing system based on mobile Internet in processing user requests was 96.2%. After nursing, the total complication rates of the control group and the observation group were 34.0% and 6.4%, the total satisfaction rates were 42.6% and 87.2%, and the referral rates were 23.4% and 6.4%, respectively, and the difference was statistically significant (P < 0.05). After nursing, the scores of self-care ability and SF-36 quality of life in the observation group were higher than those in the control group, and the difference was statistically significant (P < 0.05). In summary, the continuous nursing platform based on mobile Internet technology can meet the needs of users, and the nursing mode can significantly improve the home self-care ability of discharged patients with T-tube after surgery and improve the nursing effect, which is conducive to the rehabilitation of patients.

Iron-Promoted Oxidative Alkylation/Cyclization of Ynones with 4-Alkyl-1,4-dihydropyridines: Access to 2-Alkylated Indenones.

An iron-promoted oxidative tandem alkylation/cyclization of ynones with 4-alkyl-substituted 1,4-dihydropyridines for the efficient synthesis of 2-alkylated indenones is described. The process occurs via oxidative homolysis of a C-C σ-bond in 1,4-dihydropyridines to generate an alkyl radical followed by the addition of C-C triple bonds in ynones and intramolecular cyclization. A wide range of alkyl radicals could be efficiently transferred to generate a series of synthetically useful 2-alkylated indenones with excellent selectivity under mild conditions.

Extrachromosomal Circular DNA: A New Target in Cancer.

Genomic instability and amplification are intrinsically important traits determining the development and heterogeneity of tumors. The role of extrachromosomal circular DNA (eccDNA) in tumors has recently been highlighted. EccDNAs are unique genetic materials located off the chromosomal DNA. They have been detected in a variety of tumors. This review analyzes the mechanisms involved in the formation of eccDNAs and their genetic characteristics. In addition, the high-copy number and transcriptional levels of oncogenes located in eccDNA molecules contribute to the acceleration of tumor evolution and drug resistance and drive the development of genetic heterogeneity. Understanding the specific genomic forms of eccDNAs and characterizing their potential functions will provide new strategies for tumor therapy. Further research may yield new targets and molecular markers for the early diagnosis and treatment of human cancer.

Lipase-triggered drug release from BCL2 inhibitor ABT-199-loaded nanoparticles to elevate anti-leukemic activity through enhanced drug targeting on the mitochondrial membrane.

Selective BCL2 inhibitor ABT-199 has been approved to treat hematological malignancies including acute myeloid leukemia (AML). However, acquired drug resistance and severe side effects occur after extended treatment limiting the clinical usage of ABT-199. Here, we successfully encapsulated pure ABT-199 in amphiphilic mPEG-b-PTMC169 block copolymer, forming mPEG-b-PTMC169@ABT-199 nanoparticles (abbreviated as PEG-ABT-199), which presented better aqueous dispersion and higher efficiency of loading and encapsulation than pure ABT-199. We then compared the anti-leukemic ability of pure ABT-199 and PEG-ABT-199 in vitro and in vivo. PEG-ABT-199 had a lower IC50 value compared with pure ABT-199 in MV4-11 and MOLM-13 cell lines. In addition, PEG-ABT-199 significantly induced apoptosis and decreased colony number than pure ABT-199. Most importantly, PEG-ABT-199 markedly reduced leukemic burden, inhibited the infiltration of leukemic blasts in the spleen, and extended the overall survival (OS) in MLL-AF9-transduced murine AML compared with free ABT-199. Meanwhile, the blank PEG169 NP was non-toxic to normal hematopoiesis in vitro and in vivo, suggesting that PEG169 NP is a safe carrier. Mechanistically, PEG-ABT-199 enhanced mitochondria-targeted delivery of ABT-199 to trigger the collapse of mitochondrial membrane potential (MMP), the release of cytochrome c (cyt-c), and mitochondria-based apoptosis. In conclusion, our results suggest that PEG-ABT-199 has more vital anti-leukemic ability than pure ABT-199. PEG-ABT-199 has potential application in clinical trials to alleviate side effects and improve anti-leukemia ability. STATEMENT OF SIGNIFICANCE: ATB-199, an orally selective inhibitor for BCL2 protein, presents marked activity in relapsed or refractory AML, T-ALL, and CLL patients. However, ABT-199 resistance severely limits the further clinical usage because of off-target effects, non-specific toxicities, and low delivery of drugs. To reduce the side-effects and improve the solubility and bioavailability, ABT-199 was encapsulated into the amphiphilic mPEG-b-PTMC block copolymer by co-assembly method to obtain mPEG-b-PTMC@ABT-199 nanoparticles (PEG-ABT-199). PEG-ABT-199 has several advantages compared with pure ABT-199. 1.PEG-ABT-199 presents better aqueous dispersion and higher efficiencies of loading and encapsulation than pure ABT-199. 2. PEG-ABT-199 substantially enhances the anti-leukemic ability in vitro and in vivo compared with pure ABT-199. 3. PEG-ABT-199 has little effects on normal cells. 4. PEG-ABT-199 can reduce treatment cost.

Peritumoral matrilin-2 staining may be useful in distinguishing basal cell carcinoma from folliculocentric basaloid proliferation.

BACKGROUND: Folliculocentric basaloid proliferation (FBP) is a benign and reactive proliferation which can histopathologically mimic basal cell carcinomas (BCCs). The incidental presence of FBP during the excision of a BCC can occasionally lead to excessive tissue removal. One distinguishing feature of BCCs is that they invade the stroma, whereas FBPs generally do not. METHODS: Matrilin-2 is an extracellular matrix protein associated with tumor invasion, and we compared the expression of matrilin-2 in peritumoral cells of BCC and FBP. RESULTS: We found increased matrilin-2 expression within the peritumoral stroma of 41 of 42 BCCs (97.7%), with strong expression in all (100%) cases of infiltrative subtypes and in 21 of 25 (84%) nodular subtypes of BCC. We found no expression of peritumoral matrilin-2 in any of the seven cases of FBP. CONCLUSION: Our results suggest that immunolabeling with the matrilin-2 antibody may help distinguish BCCs from FBPs.