Cryogenic Photoelectron Spectroscopic and Theoretical Study of the Electronic and Geometric Structures of Undercoordinated Osmium Chloride Anions OsCln- (n = 3-5).

A series of anionic transition metal halides, OsCln- (n = 3-5), have been investigated using a newly developed, home-constructed, cryogenic anion cluster photoelectron spectroscopy. The target anionic species are generated through collision-induced dissociation in a two-stage ion funnel. The measured vertical detachment energies (VDEs) are 3.48, 4.54, and 4.81 eV for n = 3, 4, and 5, respectively. Density functional theory calculations at the B3LYP-D3(BJ)//aug-cc-pVTZ(-pp) level predict the lowest energy structures of the atomic form of OsCln- (n = 3-5) to be a quintet triangle, quartet square, and quintet square-based pyramid, respectively. The CCSD(T)-calculated VDEs and corresponding adiabatic detachment energies agree well with our experimental measurements. Analysis of the corresponding frontier molecular orbitals and charge density differences suggests that the d-orbitals of the transition metal Os play a primary role in the single-photon detachment processes, and the detached electrons originating from different molecular orbitals are distinguishable.

Cinnamaldehyde: Pharmacokinetics, anticancer properties and therapeutic potential (Review).

Cancer incidence is increasing globally, presenting a growing public health challenge. While anticancer drugs are crucial in treatment, their limitations, including poor targeting ability and high toxicity, hinder effectiveness and patient safety, requiring relentless scientific research and technological advancements to develop safer and more effective therapeutics. Cinnamaldehyde (CA), an active compound derived from the natural plant cinnamon, has garnered attention in pharmacological research due to its diverse therapeutic applications. CA has potential in treating a wide array of conditions, including cardiovascular diseases, diabetes, inflammatory disorders and various forms of cancer. The present review comprehensively summarizes the physicochemical and pharmacokinetic profiles of CA, and delves into the latest advancements in elucidating its potential mechanisms and targets across various cancer types. CA and its derivatives have antitumor effects, which encompass inhibiting cell proliferation, arresting the cell cycle, inducing apoptosis, limiting cell migration and invasion, and suppressing angiogenesis. Additionally, the present review explores targeted formulations of CA, laying a scientific foundation for further exploration of its implications in cancer prevention and treatment strategies.

Tumor suppressor FRMD3 controls mammary epithelial cell fate determination via notch signaling pathway.

The luminal-to-basal transition in mammary epithelial cells (MECs) is accompanied by changes in epithelial cell lineage plasticity; however, the underlying mechanism remains elusive. Here, we report that deficiency of Frmd3 inhibits mammary gland lineage development and induces stemness of MECs, subsequently leading to the occurrence of triple-negative breast cancer. Loss of Frmd3 in PyMT mice results in a luminal-to-basal transition phenotype. Single-cell RNA sequencing of MECs indicated that knockout of Frmd3 inhibits the Notch signaling pathway. Mechanistically, FERM domain-containing protein 3 (FRMD3) promotes the degradation of Disheveled-2 by disrupting its interaction with deubiquitinase USP9x. FRMD3 also interrupts the interaction of Disheveled-2 with CK1, FOXK1/2, and NICD and decreases Disheveled-2 phosphorylation and nuclear localization, thereby impairing Notch-dependent luminal epithelial lineage plasticity in MECs. A low level of FRMD3 predicts poor outcomes for breast cancer patients. Together, we demonstrated that FRMD3 is a tumor suppressor that functions as an endogenous activator of the Notch signaling pathway, facilitating the basal-to-luminal transformation in MECs.

HMGA2 promotes resistance against paclitaxel by targeting the p53 signaling pathway in colorectal cancer cells.

Colorectal cancer is one of the most common malignancies and ranks second in terms of cancer-related mortality worldwide due to its metastasis, drug resistance, and reoccurrence. High-mobility gene group A2 (HMGA2) is overexpressed in colorectal cancer, contributing to the aggressiveness of tumor malignance, and promotes drug resistance in many types of cancer. However, the underlying molecular mechanism of HMGA2 is yet to be elucidated. In this study, we showed that HMGA2 is overexpressed in colorectal cancer tissue, and knockdown of HMGA2 significantly inhibited colorectal cancer cell growth and migratory capability. HMGA2 regulates the cancer cell response to a widely used anti-cancer drug, paclitaxel (PTX). HMGA2 knockdown increased cell death, whereas HMGA2 overexpression decreased cell death after PTX treatment. Furthermore, lower reactive oxygen species (ROS) levels and mitochondrial potential were detected in HMGA2 overexpression cells after PTX treatment. However, HMGA2 knockdown produced the opposite effect. RNA sequencing showed a p53 signaling pathway-dependent regulation in HMGA2 knockdown cells. Combined with p53 inhibitors and HMGA2 knockdown, a synergetic effect of more cell death was observed in colorectal cancer cells after PTX treatment. Thus, we showed that HMGA2 can activate p53 signaling to regulate colorectal cancer cell death after PTX treatment. Altogether, our results reveal novel insights into the molecular mechanisms underlying HMGA2-mediated cancer cell resistance against PTX and highlight the potential of targeting HMGA2 and p53 signaling for the therapeutic investigation of colorectal cancer.

The Role of Bacteria in Central Nervous System Tumors: Opportunities and Challenges.

Tumors of the central nervous system (CNS) are severe and refractory diseases with poor prognosis, especially for patients with malignant glioblastoma and brain metastases. Currently, numerous studies have explored the potential role of bacteria and intestinal flora in tumor development and treatment. Bacteria can penetrate the blood-brain barrier (BBB), targeting the hypoxic microenvironment at the core of tumors, thereby eliminating tumors and activating both the innate and adaptive immune responses, rendering them promising therapeutic agents for CNS tumors. In addition, engineered bacteria and derivatives, such as bacterial membrane proteins and bacterial spores, can also be used as good candidate carriers for targeted drug delivery. Moreover, the intestinal flora can regulate CNS tumor metabolism and influence the immune microenvironment through the "gut-brain axis". Therefore, bacterial anti-tumor therapy, engineered bacterial targeted drug delivery, and intervention of the intestinal flora provide therapeutic modalities for the treatment of CNS tumors. In this paper, we performed a comprehensive review of the mechanisms and therapeutic practices of bacterial therapy for CNS tumors and discussed potential future research directions in this field.

Disrupted Dynamic Network Attribution Associated with Gait Disorder in Cerebral Small Vessel Disease.

Background and Aims: Previous research has focused on static functional connectivity in gait disorders caused by cerebral small vessel disease (CSVD), neglecting dynamic functional connections and network attribution. This study aims to investigate alterations in dynamic functional network connectivity (dFNC) and topological organization variance in CSVD-related gait disorders. Methods: A total of 85 patients with CSVD, including 41 patients with CSVD and gait disorders (CSVD-GD), 44 patients with CSVD and non-gait disorders (CSVD-NGD), and 32 healthy controls (HC), were enrolled in this study. Five networks composed of 10 independent components were selected using independent component analysis. Sliding time window and k-means clustering methods were used for dFNC analysis. The relationship between alterations in the dFNC properties and gait metrics was further assessed. Results: Three reproducible dFNC states were determined (State 1: sparsely connected, State 2: intermediate pattern, and State 3: strongly connected). CSVD-GD showed significantly higher fractional windows (FW) and mean dwell time (MDT) in State 1 compared with CSVD-NGD. Higher local efficiency variance was observed in the CSVD-GD group compared with HC, but no differences were found in the global efficiency comparison. Both the FW and MDT in State 1 were negatively correlated with gait speed and step length, and the relationship between MDT of State 1 and gait speed was mediated by overall cognition, information processing speed, and executive function. Conclusions: Our study uncovered abnormal dFNC indicators and variations in topological organization in CSVD-GD, offering potential early prediction indicators and freshening insights into the underlying pathogenesis of gait disturbances in CSVD.

Establishment of a Dual-Signal Enhanced Fluorescent Aptasensor for Highly Sensitive Detection of Ochratoxin A.

A robust and versatile dual-signal enhanced fluorescent aptasensor was developed for ochratoxin A (OTA) detection based on fluorescence resonance energy transfer between 5-carboxyfluorescein (FAM) and Super Green I (SG) fluorophores as the donor and graphene oxide (GO) nanosheet as the acceptor. Abundant SG probes were adsorbed into the FAM-complementary DNA (cDNA)-aptamer double-stranded structure to achieve remarkably enhanced fluorescence responses. Without OTA, the FAM-cDNA-SG conjugates coexisted with GO nanosheets, exhibiting strong fluorescence signals. In the presence of OTA, it was captured by the aptamers to release cDNA-FAM and SG probes, which were adsorbed by GO, leading to OTA-dependent fluorescence quenching. The changed fluorescence intensity was measured for accurate quantitation of OTA. Under optimum conditions, the dual-signal enhanced fluorescent aptasensor realized fascinating sensitivity with a limit of detection of 0.005 ng/mL and a wide concentration range of 0.02-20 ng/mL, as well as high selectivity for OTA over other interfering substances, excellent accuracy with average recoveries of 91.37-116.83% in the fortified malt matrices, and superior reliability and practicability in actual samples. This FAM-cDNA-aptamer-SG/GO nanosheet-based aptasensing platform could be extended to monitor other contaminants or trace molecules in food, environmental, and diagnostic fields by altering the corresponding aptamers.

Multiple functions of HMGB1 in cancer.

High mobility group box 1 (HMGB1) is a nuclear DNA-binding protein with a dual role in cancer, acting as an oncogene and a tumor suppressor. This protein regulates nucleosomal structure, DNA damage repair, and genomic stability within the cell, while also playing a role in immune cell functions. This review comprehensively evaluates the biological and clinical significance of HMGB1 in cancer, including its involvement in cell death and survival, its potential as a therapeutic target and cancer biomarker, and as a prosurvival signal for the remaining cells after exposure to cytotoxic anticancer treatments. We highlight the need for a better understanding of the cellular markers and mechanisms involved in the involvement of HMGB1in cancer, and aim to provide a deeper understanding of its role in cancer progression.

Causal relationship between circulating cytokines and follicular lymphoma: a two-sample Mendelian randomization study.

Follicular lymphoma (FL), derived from germinal centre (GC) B cells, is a kind of systemic neoplasm. Even though FL is indolent, it remains an incurable haematology Neoplasm. Accumulating evidence has suggested that the circulating cytokine is associated with the development of FL, yet the causal relationship between FL and circulating cytokines remains undetermined. Therefore, we conducted a two-sample Mendelian randomization (MR) to confirm the causal link between FL and levels of circulating cytokines with the use of summary data on circulating cytokines and FL. All these data from genome-wide association study were derived from the Genome-wide pQTL mapping which contains 14,824 individuals. FL data were acquired exclusively from FinnGen, where 218,792 individuals (522 cases vs. 218,270 controls) were involved. Various statistical methods, including the inverse variance weighted method (IVW), weighted median (WME), simple model, weighted model (WM) and MR-Egger, were used to evaluate the potential causal connection between circulating cytokines and FL. Sensitivity analysis, which involves the examination of the heterogeneity, pleiotropy, and leave-one-out method, was also performed to ensure more trustworthy results. A bidirectional MR test was performed to evaluate the direction of causal association between circulating cytokines and FL. Combining all the steps of MR analysis, we revealed four causal cytokines: C-X-C motif chemokine ligand 5 (CXCL5), interleukin-15 receptor A (IL15RA), interleukin-20 (IL20), and neurotrophin-3 (NT-3). The risk of FL may be inversely linked to CXCL5 (OR=0.73, CI: 0.545-0.979, P=0.036), IL-15RA (OR=0.669, CI: 0.451-0.993, P=0.046), and IL-20 (OR=0.565, CI: 0.325-0.981, P=0.043) but positively linked to NT-3 (OR=1.872, CI: 1.063-3.297, P=0.03). In addition, in our study, no causal effect of FL on cytokines was demonstrated and no significant heterogeneity and pleiotropy were found. Our research revealed the causal relationship between cytokines and FL, along with both the anti-protective effect of CXCL5, IL-15RA, and IL-20 and the protective effect of neurotrophin-3 on FL. These findings aim to provide new clues regarding the pathogenesis of FL and to extend the potential of circulating cytokines to therapeutic interventions.

Rapid response of fly populations to gene dosage across development and generations.

Although the effects of genetic and environmental perturbations on multicellular organisms are rarely restricted to single phenotypic layers, our current understanding of how developmental programs react to these challenges remains limited. Here, we have examined the phenotypic consequences of disturbing the bicoid regulatory network in early Drosophila embryos. We generated flies with two extra copies of bicoid, which causes a posterior shift of the network's regulatory outputs and a decrease in fitness. We subjected these flies to EMS mutagenesis, followed by experimental evolution. After only 8-15 generations, experimental populations have normalized patterns of gene expression and increased survival. Using a phenomics approach, we find that populations were normalized through rapid increases in embryo size driven by maternal changes in metabolism and ovariole development. We extend our results to additional populations of flies, demonstrating predictability. Together, our results necessitate a broader view of regulatory network evolution at the systems level.

Tea Polysaccharide Ameliorates High-Fat Diet-Induced Renal Tubular Ectopic Lipid Deposition via Regulating the Dynamic Balance of Lipogenesis and Lipolysis.

Renal tubular ectopic lipid deposition (ELD) plays a significant role in the development of chronic kidney disease, posing a great threat to human health. The present work aimed to explore the intervention effect and potential molecular mechanism of a purified tea polysaccharide (TPS3A) on renal tubular ELD. The results demonstrated that TPS3A effectively improved kidney function and slowed the progression of tubulointerstitial fibrosis in high-fat-diet (HFD)-exposed ApoE-/- mice. Additionally, TPS3A notably suppressed lipogenesis and enhanced lipolysis, as shown by the downregulation of lipogenesis markers (SREBP-1 and FAS) and the upregulation of lipolysis markers (HSL and ATGL), thereby reducing renal tubular ELD in HFD-fed ApoE-/- mice and palmitic-acid-stimulated HK-2 cells. The AMPK-SIRT1-FoxO1 axis is a core signal pathway in regulating lipid deposition. Consistently, TPS3A significantly increased the levels of phosphorylated-AMPK, SIRT1, and deacetylation of Ac-FoxO1. However, these effects of TPS3A on lipogenesis and lipolysis were abolished by AMPK siRNA, SIRT1 siRNA, and FoxO1 inhibitor, resulting in exacerbated lipid deposition. Taken together, TPS3A shows promise in ameliorating renal tubular ELD by inhibiting lipogenesis and promoting lipolysis through the AMPK-SIRT1-FoxO1 signaling pathway.

Effects of Phloroglucinol on Embryo Transfer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Phloroglucinol may be able to improve embryo transfer outcomes. We aimed to systematically evaluate the effects of phloroglucinol on embryo transfer outcomes. METHODS: The databases searched were PubMed, Ovid MEDLINE, Web of Science, Wanfang, CQVIP, China National Knowledge Infrastructure, and ClinicalTrials.gov. The last search was on February 7, 2023. The included studies were written in English or Chinese. Randomized controlled trials and cohort studies aiming to assess the effect of phloroglucinol on embryo transfer outcomes were included. The studies reported at least one of the primary outcomes (biochemical pregnancy rate, clinical pregnancy rate, and live birth rate). The odds ratio (OR) and 95% confidence interval (CI) were calculated. A random-effects or fixed model was used where applicable to estimate the results. RESULTS: Seventeen articles reporting 5,953 cycles were included. Biochemical pregnancy rate (OR = 1.58, 95% CI = 1.20-2.08, I2 = 71%), clinical pregnancy rate (OR = 1.69, 95% CI = 1.35-2.10, I2 = 64%), and live birth rate (OR = 1.45, 95% CI = 1.23-1.71, I2 = 36%) were improved by phloroglucinol. Less miscarriage (OR = 0.46, 95% CI = 0.35-0.60, I2 = 0%), less ectopic pregnancy (OR = 0.45, 95% CI = 0.28-0.72, I2 = 0%), higher implantation rate (OR = 1.45, 95% CI = 1.24-1.71, I2 = 62%) but more multiple pregnancy rate (OR = 1.48, 95% CI = 1.13-1.94, I2 = 0%) were induced by phloroglucinol. Endometrial peristaltic waves were improved by phloroglucinol (OR = 22.87, 95% CI = 5.52-94.74, I2 = 72%). CONCLUSION: Phloroglucinol may improve the outcomes of embryo transfer, including biochemical pregnancy, clinical pregnancy, and live birth rates. Further studies are warranted.

Two swords combination: Smartphone-assisted ratiometric fluorescent and paper sensors for dual-mode detection of glyphosate in edible malt.

The long-term and excessive use of glyphosate (GLY) in diverse matrices has caused serious hazard to the human and environment. However, the ultrasensitive detection of GLY still remains challenging. In this study, the smartphone-assisted dual-signal mode ratiometric fluorescent and paper sensors based on the red-emissive gold nanoclusters (R-AuNCs) and blue-emissive carbon dots (B-CDs) were ingeniously designed accurate and sensitive detection of GLY. Upon the presence of GLY, it would quench the fluorescence of B-CDs through dynamic quenching effect, and strengthen the fluorescence response of R-AuNCs due to aggregation-induced enhancement effect. Through calculating the GLY-induced fluorescence intensity ratio of B-CDs to R-AuNCs by using a fluorescence spectrophotometer, low to 0.218 µg/mL of GLY could be detected in lab in a wide concentration range of 0.3-12 µg/mL with high recovery of 94.7-103.1% in the spiked malt samples. The smartphone-assisted ratiometric fluorescent sensor achieved in the 96-well plate could monitor 0-11 µg/mL of GLY with satisfactory recovery of 94.1-107.0% in real edible malt matrices for high-throughput analysis. In addition, a portable smartphone-assisted ratiometric paper sensor established through directly depositing the combined B-CDs/R-AuNCs probes on the test strip could realize on-site measurement of 2-8 µg/mL of GLY with good linear relationship. This study provides new insights into developing the dual-signal ratiometric sensing platforms for the in-lab sensitive detection, high-throughput analysis, and on-site portable measurement of more trace contaminants in foods, clinical and environmental samples.

HER2-targeting CAR-T cells show highly efficient anti-tumor activity against glioblastoma both in vitro and in vivo.

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Current treatment options for GBM include surgical resection, radiation, and chemotherapy, which predominantly slow cancer growth and reduce symptoms, resulting in a 5-year survival rate of no more than 10%. Chimeric antigen receptor (CAR) T-cell therapy is a new class of cellular immunotherapy that has made great progress in treating malignant tumors. Human epidermal growth factor receptor 2 (HER2) is overexpressed in GBM and may provide a potential therapeutic target for GBM treatment. In this study, we constructed third-generation CAR-T cells targeting the HER2 antigen in GBM. HER2-CAR-T cells showed effective anti-tumor activity both in vitro and in vivo. Furthermore, HER2-specific CAR-T cells exhibited strong cytotoxicity and cytokine-secreting abilities against GBM cells in vitro. Anti-HER2 CAR-T cells also exhibited increased cytotoxicity with increasing effector-to-target ratios. Anti-HER2 CAR-T cells delivered via peritumoral injection successfully stunted tumor progression in vivo. Moreover, peritumoral intravenous administration of anti-HER2 CAR-T cells resulted in therapeutic improvement against GBM cells compared with intravenous administration. In conclusion, our study shows that HER2 CAR-T cells represent an emerging immunotherapy for treating GBM.

Comparative quantitative analysis of optical coherence tomography angiography in varied morphologies of macular neovascularization following intravitreal conbercept and ranibizumab treatments for neovascular age­related macular degeneration.

The present study aimed to examine the optical coherence tomography angiography (OCTA) parameters associated with macular neovascularization (MNV) in patients diagnosed with neovascular age-related macular degeneration (nAMD) and treated with either intravitreal conbercept (IVC) or ranibizumab (IVR). It enrolled 39 nAMD patients presenting with MNV, including 23 in the IVC group and 16 in the IVR group. All participants were treatment-naïve with intravitreal therapy and they underwent treatment following a '3+PRN' regimen. The MNV patterns identified through OCTA were categorized as Medusa, tangled, seafan and other variations. Key outcome measures encompassed best-corrected visual acuity (BCVA), MNV vascular area (MNV-VA), MNV vascular density (MNV-VD) ratio and central macular thickness (CMT). In the present study, 44 eyes were included, with 28 eyes undergoing treatment with IVC and 18 eyes with IVR. On day 90, there was a statistically significant improvement in mean BCVA from baseline among all patients treated with IVC (P=0.002). Notably, improved outcomes were observed in those with the 'tangled' pattern compared with the other three patterns (P=0.007). CMT exhibited a significant decrease from baseline (P=0.007), with consistent improvement observed across all four patterns (P=0.052) on day 90. The mean MNV-VA decreased in all patients, reaching statistical significance for the Medusa pattern (P=0.008), although the improvement in visual acuity was deemed unsatisfactory. Patients with the seafan pattern treated with IVR improved significantly in BCVA (P=0.042). The mean CMT significantly improved from baseline (P=0.001), consistent across the four patterns (P=0.114). Significant improvements were noted in the mean MNV-VA for the seafan pattern and in the mean MNV-VD ratio for the other patterns. The two regimens had no significant differences regarding BCVA, CMT, and MNV parameters. Conbercept emerged as a viable treatment option for patients presenting with tangled MNV patterns. On the other hand, ranibizumab might be considered an effective intervention for individuals with seafan MNV patterns. Notably, the Medusa MNV pattern was associated with a morphologic configuration indicative of a poor prognosis.

The effect of metabolism-related lifestyle and clinical risk factors on digestive system cancers in East Asian populations: a two-sample Mendelian randomization analysis.

Metabolic factors play a critical role in the development of digestive system cancers (DSCs), and East Asia has the highest incidence of malignant tumors in the digestive system. We performed a two-sample Mendelian randomization analysis to explore the associations between 19 metabolism-related lifestyle and clinical risk factors and DSCs, including esophageal, gastric, colorectal, hepatocellular, biliary tract, and pancreatic cancer. The causal association was explored for all combinations of each risk factor and each DSC. We gathered information on the instrumental variables (IVs) from various sources and retrieved outcome information from Biobank Japan (BBJ). The data were all from studies of east Asian populations. Finally, 17,572 DSCs cases and 195,745 controls were included. Our analysis found that genetically predicted alcohol drinking was a strong indicator of gastric cancer (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.93-0.98) and hepatocellular carcinoma (OR = 1.11; 95% CI: 1.05-1.18), whereas coffee consumption had a potential protective effect on hepatocellular carcinoma (OR = 0.69; 95% CI: 0.53-0.90). Triglyceride was potentially associated with a decreased risk of biliary tract cancer (OR = 0.53; 95% CI: 0.34-0.81), and uric acid was associated with pancreatic cancer risk (OR = 0.59; 95% CI: 0.37-0.96). Metabolic syndrome (MetS) was associated with esophageal and gastric cancer. Additionally, there was no evidence for a causal association between other risk factors, including body mass index, waist circumference, waist-to-hip ratio, educational levels, lipoprotein cholesterol, total cholesterol, glycine, creatinine, gout, and Graves' disease, and DSCs. The leave-one-out analysis revealed that the single nucleotide polymorphism (SNP) rs671 from the ALDH2 gene has a disproportionately high contribution to the causal association between alcohol drinking and gastric cancer and hepatocellular carcinoma, as well as the association between coffee consumption and hepatocellular carcinoma. The present study revealed multiple metabolism-related lifestyle and clinical risk factors and a valuable SNP rs671 for DSCs, highlighting the significance of metabolic factors in both the prevention and treatment of DSCs.

A novel biopsy scheme for prostate cancer: targeted and regional systematic biopsy.

PURPOSE: To explore a novel biopsy scheme for prostate cancer (PCa), and test the detection rate and pathological agreement of standard systematic (SB) + targeted (TB) biopsy and novel biopsy scheme. METHODS: Positive needles were collected from 194 patients who underwent SB + TB (STB) followed by radical prostatectomy (RP). Our novel biopsy scheme, targeted and regional systematic biopsy (TrSB) was defined as TB + regional SB (4 SB-needles closest to the TB-needles). The McNemar test was utilized to compare the detection rate performance for clinical significant PCa (csPCa) and clinical insignificant PCa (ciPCa). Moreover, the accuracy, positive predictive value (PPV) and negative predictive value (NPV) were investigated. The agreement between the different biopsy schemes grade group (GG) and RP GG were assessed. The concordance between the biopsy and the RP GG was evaluated using weighted κ coefficient analyses. RESULTS: In this study, the overall detection rate for csPCa was 83.5% (162 of 194) when SB and TB were combined. TrSB showed better NPV than TB (97.0% vs. 74.4%). Comparing to STB, the TB-detection rate of csPCa had a significant difference (p < 0.01), while TrSB showed no significant difference (p > 0.999). For ciPCa, the overall detection rate was 16.5% (32 of 194). TrSB showed better PPV (96.6% vs. 83.3%) and NPV (97.6% vs. 92.9%) than TB. Comparing to STB, the detection rate of both schemes showed no significant difference (p = 0.077 and p = 0.375). All three schemes GG showed poor agreement with RP GG (TB: 43.3%, TrSB: 46.4%, STB: 45.9%). Using weighted κ, all three schemes showed no difference (TB: 0.48, TrSB: 0.51, STB: 0.51). In our subgroup analysis (PI-RADS = 4/5, n = 154), all three schemes almost showed no difference (Weighted κ: TB-0.50, TrSB-0.51, STB-0.50). CONCLUSION: Our novel biopsy scheme TrSB (TB + 4 closest SB needles) may reduce 8 cores of biopsy compared with STB (standard SB + TB), which also showed better csPCa detection rate than TB only, but the same as STB. The pathological agreement between three different biopsy schemes (TB/TrSB/STB) GG and RP GG showed no difference.

Long-term outcomes of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): a randomized, multicenter, prospective, phase III trial.

BACKGROUND: We aimed to compare combined intraoperative chemotherapy and surgical resection with curative surgical resection alone in colorectal cancer patients. METHODS: We performed a multicenter, open-label, randomized, phase III trial. All eligible patients were randomized and assigned to intraoperative chemotherapy and curative surgical resection or curative surgical resection alone (1:1). Survival actualization after long-term follow-up was performed in patients analyzed on an intention-to-treat basis. RESULTS: From January 2011 to January 2016, 696 colorectal cancer patients were enrolled and randomly assigned to intraoperative chemotherapy and radical surgical resection (n=341) or curative surgical resection alone (n=344). Intraoperative chemotherapy with surgical resection showed no significant survival benefit over surgical resection alone in colorectal cancer patients (3-year DFS: 91.1% vs. 90.0%, P=0.328; 3-year OS: 94.4% vs. 95.9%, P=0.756). However, colon cancer patients benefitted from intraoperative chemotherapy, with a relative 4% reduction in liver and peritoneal metastasis (HR=0.336, 95% CI: 0.148-0.759, P=0.015) and a 6.5% improvement in 3-year DFS (HR=0.579, 95% CI: 0.353-0.949, P=0.032). Meanwhile, patients with colon cancer and abnormal pretreatment CEA levels achieved significant survival benefits from intraoperative chemotherapy (DFS: HR=0.464, 95% CI: 0.233-0.921, P=0.029 and OS: (HR=0.476, 95% CI: 0.223-1.017, P=0.049). CONCLUSIONS: Intraoperative chemotherapy showed no significant extra prognostic benefit in total colorectal cancer patients who underwent radical surgical resection; however, in colon cancer patients with abnormal pretreatment serum CEA levels (> 5 ng/ml), intraoperative chemotherapy could improve long-term survival.

Age and mean platelet volume-based nomogram for predicting the therapeutic efficacy of metoprolol in Chinese pediatric patients with vasovagal syncope.

BACKGROUND: Vasovagal syncope (VVS) is the most common type of orthostatic intolerance in children. We investigated whether platelet-related factors related to treatment efficacy in children suffering from VVS treated with metoprolol. METHODS: Metoprolol-treated VVS patients were recruited. The median duration of therapy was three months. Patients were followed and divided into two groups, treament-effective group and treatment-ineffective group. Logistic and least absolute shrinkage selection operator regressions were used to examine treatment outcome variables. Receiver-operating characteristic (ROC) curves, precision-recall (PR) curves, calibration plots, and decision curve analyses were used to evaluate the nomogram model. RESULTS: Among the 72 patients who complete the follow-up, treatment-effective group and treatment-ineffective group included 42 (58.3%) and 30 (41.7%) cases, respectively. The patients in the treatment-effective group exhibited higher mean platelet volume (MPV) [(11.0 ± 1.0) fl vs. (9.8 ± 1.0) fl, P < 0.01] and platelet distribution width [12.7% (12.3%, 14.3%) vs. 11.3% (10.2%, 12.2%), P < 0.01] than those in the treatment-ineffective group. The sex ratio was significantly different (P = 0.046). A fit model comprising age [odds ratio (OR) = 0.766, 95% confidence interval (CI) = 0.594-0.987] and MPV (OR = 5.613, 95% CI = 2.297-13.711) might predict therapeutic efficacy. The area under the curve of the ROC and PR curves was computed to be 0.85 and 0.9, respectively. The P value of the Hosmer-Lemeshow test was 0.27. The decision curve analysis confirmed that managing children with VVS based on the predictive model led to a net advantage ranging from 0.01 to 0.58. The nomogram is convenient for clinical applications. CONCLUSION: A novel nomogram based on age and MPV can predict the therapeutic benefits of metoprolol in children with VVS.