A Tumor Environment-Activated Photosensitized Biomimetic Nanoplatform for Precise Photodynamic Immunotherapy of Colon Cancer.

Aggressive nature of colon cancer and current imprecise therapeutic scenarios simulate the development of precise and effective treatment strategies. To achieve this, a tumor environment-activated photosensitized biomimetic nanoplatform (PEG2000-SiNcTI-Ph/CpG-ZIF-8@CM) is fabricated by encapsulating metal-organic framework loaded with developed photosensitizer PEG2000-SiNcTI-Ph and immunoadjuvant CpG oligodeoxynucleotide within fusion cell membrane expressing programmed death protein 1 (PD-1) and cluster of differentiation 47 (CD47). By stumbling across, systematic evaluation, and deciphering with quantum chemical calculations, a unique attribute of tumor environment (low pH plus high concentrations of adenosine 5'-triphosphate (ATP))-activated photodynamic effect sensitized by long-wavelength photons is validated for PEG2000-SiNcTI-Ph/CpG-ZIF-8@CM, advancing the precision of cancer therapy. Moreover, PEG2000-SiNcTI-Ph/CpG-ZIF-8@CM evades immune surveillance to target CT26 colon tumors in mice mediated by CD47/signal regulatory proteins α (SIRPα) interaction and PD-1/programmed death ligand 1 (PD-L1) interaction, respectively. Tumor environment-activated photodynamic therapy realized by PEG2000-SiNcTI-Ph/CpG-ZIF-8@CM induces immunogenic cell death (ICD) to elicit anti-tumor immune response, which is empowered by enhanced dendritic cells (DC) uptake of CpG and PD-L1 blockade contributed by the nanoplatform. The photodynamic immunotherapy efficiently combats primary and distant CT26 tumors, and additionally generates immune memory to inhibit tumor recurrence and metastasis. The nanoplatform developed here provides insights for the development of precise cancer therapeutic strategies.

Trends in suicide mortality among cancer survivors in the US, 1975-2020.

BACKGROUND: Suicide in cancer survivors is a major public health concern, but its trends and risk factors are not well understood. This study aimed to investigate the standardized mortality rate (SMR) and trends in suicide among cancer survivors in the United States. METHODS: Using data from the SEER-9 database and US Mortality data, we identified 3,684,040 cancer survivors diagnosed between 1975 and 2020. The SMR of suicide among cancer survivors was calculated, and Poisson regression analysis was used to evaluate trends in suicide risk. Subgroup analyses were performed based on age, gender, race, tumor site, and stage. A competing risk model was used to calculate the 10-year cumulative incidence of suicide. RESULTS: Among cancer survivors, the overall SMR of suicide was 1.49 (95%CI: 1.46-1.53) times higher than that of the general population in the US. The risk of suicide varied significantly by cancer site, with the highest risk found in patients with malignant respiratory system cancer. Overall, we observed a significant downward trend in the suicide mortality rate among cancer patients. The cumulative incidence of suicide mortality among cancer survivors across four study periods exhibited significant statistical differences (P<0.001). CONCLUSIONS: Our study highlights the need for targeted suicide prevention efforts for cancer survivors, particularly those diagnosed with respiratory system cancer. The trend of declining suicide mortality rates among cancer survivors is promising, but continued efforts are needed to understand and address the underlying risk factors.

Trends in suicide mortality among prostate cancer survivors in the United States, 1975-2019.

BACKGROUND: Suicide was an important cause of death in prostate cancer. This study intended to investigate trends in suicide mortality among prostate cancer (PCa) survivors from 1975 to 2019 in the United States. METHOD: We identified PCa survivors from the Surveillance, Epidemiology, and End Results (SEER) program from January 1975 to December 2019. Standardized mortality rate (SMR) was calculated d to assess the relative risk of suicide in PCa survivors compared with the general men population. Poisson regression model was performed to test for trend of SMRs. The cumulative mortality rate of suicide was calculated to assess the clinical burden of suicide mortality. RESULTS: 7108 (0.2%) cases were death from suicide cause, and 2,308,923(65.04%%) cases recorded as dying from non-suicidal causes. Overall, a slightly higher suicide mortality rate among PCa survivors was observed compared with general male population (SMR: 1.15, 95%CI: 1.09-1.2). The suicide mortality rate declined significantly relative to the general population by the calendar year of diagnosis, from an SMR of 1.74(95%CI: 1.17-2.51) in 1975-1979 to 0.99(0.89-1.1) in 2015-2019 (Ptrend < 0.001). PCa survivors with aged over 84 years, black and other races, registered in registrations (including Utah, New Mexico, and Hawaii) failed to observe a decrease in suicide mortality (Ptrend > 0.05). The cumulative suicide mortality during 1975-1994 was distinctly higher than in 1995-2019(P < 0.001). CONCLUSION: The trend in suicide mortality declined significantly from 1975 to 2019 among PCa survivors compared with the general male population in the United States. Notably, part of PCa survivors had no improvement in suicide mortality, and additional studies in the future were needed to explore it.

Vertical impedance electrode array for spatiotemporal dynamics monitoring of 3D cells under drug diffusion effect.

Although three-dimensional (3D) tumor models feature more accurate responses to drugs, the Matrigel scaffold affects the drug diffusion effect. Obtaining accurate drug spatiotemporal response characteristics is of great significance in the drug screening domain. However, the conventional cell-based sensors are difficult to perform spatiotemporal dynamics impedance monitoring of 3D cells and evaluate the anti-cancer pharmacological effect. Here, we proposed a biosensing platform involving a vertical impedance electrode array (VIEA) chip and a multichannel detection system. The platform can dynamically record 3D cell impedance in the vertical direction, which is consistent with time- and location-dependent drug penetration, closely related to spatiotemporal cell viability under drug effects. The subtle changes of impedance signals in different locations induced by drug diffusion can be detected, which demonstrates its high performance in drug systematic evaluation. The universal and high-content 3D cell biosensing platform is believed to have promising potential in pharmacodynamics investigation and preclinical drug screening.

Assessing the prognostic impact of prostatic urethra involvement and developing a nomogram for T1 stage bladder cancer.

PURPOSE: To investigate prognostic values of prostatic urethra involvement (PUI) and construct a prognostic model that estimates the probability of cancer-specific survival for T1 bladder cancer patients. METHOD AND MATERIALS: We investigated the national Surveillance, Epidemiology, and End Results (SEER) database (2004-2015) to get patients diagnosed with T1 bladder cancer. An external validation cohort was obtained from the First Affiliated Hospital of Nanchang University. The Kaplan-Meier method with the log-rank test was applied to assess cancer-specific survival (CSS) and overall survival (OS). Moreover, the propensity score matching (PSM) and multivariable Cox proportional hazard model were performed. All patients were randomly divided into the development cohort and validation group at the ratio of 7:3. The performance of the model was internally validated by calibration curves and the concordance index (C-index). RESULTS: The PUI group had a lower survival rate of both CSS and overall survival OS before and after PSM when compared to non-involved patients (All P < 0.05). Multivariate analysis revealed a poor prognosis in the PUI group for cancer-specific mortality (CSM) and all-cause mortality (ACM) analyses before and after PSM (All P < 0.05). Seven variables, including age, surgery, radiotherapy, tumour size, PUI, and marital status, were incorporated in the final nomogram. The C-index in the development cohort was 0.715 (0.711-0.719), while it was 0.672 (0.667-0.677) in the validation group. Calibration plots for 3- and 5-year cancer-specific survival showed good concordance in the development and validation cohorts. CONCLUSIONS: PUI was an independent risk factor of ACM and CSM in T1 bladder cancer patients. In addition, a highly discriminative and precise nomogram that predicted the individualized probability of cancer-specific survival for patients with T1 bladder cancer was constructed.

A Study on the Efficacy of Ω Toenail Correction Treating Paronychia.

To study the clinical effects of Ω toenail correction in the treatment of paronychia. One hundred thirty-six cases of 130 patients during the period from August 2018 to August 2021 were treated with Ω toenail correction according to clinical stages, the clinical therapeutic effects of which were evaluated in terms of the operation time, the time to resume movement, treatment cycle, 1-y recurrence rate, and visual analogue scale (VAS) scores before and after treatment. The clinical efficacy was analyzed and compared of Ω toenail correction in treating paronychia of different clinical stages. It has been demonstrated that there was no significant difference in operation time, time to resume movement, treatment cycle and recurrence rate among different stages of paronychia, while there existed the significant difference (p < .05) in VAS score of resting-state pain before and after correction which stood at 6.43 ± 0.29 points with the after-treatment VAS scores at 1.10 ± 0.22. There is a statistical difference (p < .05) in VAS score of movement-evoked pain between before and after treatment. The VAS scores of movement-evoked pain stood at 7.55 ± 0.42, which is in contrast with the after-treatment VAS at 1.74 ± 0.93. It has been concluded that Ω toenail correction characterized by easy operation can relieve the pain immediately, which can achieve satisfactory clinical efficacy for treating paronychia of different stages.

[Integrated management during the perinatal period for total anomalous pulmonary venous connection]. / å®Œå ¨æ€§è‚ºé™è„‰å¼‚ä½è¿žæŽ¥çš„å›´ç”ŸæœŸä¸€ä½“åŒ–ç®¡ç†.

OBJECTIVES: To evaluate the clinical effectiveness of integrated management during the perinatal period for fetuses diagnosed with total anomalous pulmonary venous connection (TAPVC) by prenatal echocardiography. METHODS: Clinical data of 64 cases of TAPVC fetuses diagnosed by prenatal echocardiography and managed with integrated perinatal care in Qingdao Women and Children's Hospital from January 2017 to December 2021 were retrospectively analyzed. Integrated perinatal care included multidisciplinary collaboration among obstetrics, fetal medicine, ultrasound, pediatric cardiology, pediatric anesthesia, and neonatology. RESULTS: Among the 64 TAPVC fetuses, there were 29 cases of supracardiac type, 27 cases of intracardiac type, 2 cases of infracardiac type, and 6 cases of mixed type. Chromosomal analysis was performed in 42 cases, and no obvious abnormalities were found. Among the 64 TAPVC fetuses, 37 were induced labor, and 27 were followed up until term birth. Among the 27 TAPVC cases, 2 cases accepted palliative care, 2 cases were referred to another hospital for treatment and lost to follow-up, while the remaining 23 cases underwent primary repair surgery. One case died within 6 months after the operation due to low cardiac output syndrome, while the other 22 cases were followed up for (2.1±0.3) years with good outcomes (2 cases underwent a second surgery within 1 year after the first operation due to anastomotic stenosis or pulmonary vein stenosis). CONCLUSIONS: TAPVC fetuses can achieve good outcomes with integrated management during the perinatal period.

Model for predicting prognosis and immunotherapy based on CD+8 T cells infiltration in neuroblastoma.

BACKGROUND: Neuroblastoma (NBL) is an extracranial malignant tumor in children deriving from the neural crest in the sympathetic nervous system. Although various immunotherapy interventions have made significant breakthroughs in many adult cancers, the efficacy of these immunotherapies was still limited in NBL. NBL has low immunogenicity which results in a lack of tumor-infiltrating T lymphocytes in the tumor microenvironment (TME). Moreover, tumor cells can wield many immune evasion strategies both in the TME and systemically to impede lymphocyte infiltration and activation. All these factors hamper the anti-tumor effects of CD8+ T cells during immunotherapy and the levels of infiltrating CD8+ T cells correlate with therapy response. MATERIALS AND METHODS: In this study, we utilized multidimensional bioinformatic methods to establish a risk model based on CD8+ T cells -related genes (CD8+ TRGs). RESULTS: We obtained 33 CD8+ TRGs with well-predictive ability for prognosis in both GSE49711 and E-MTAB-8248 cohorts. Then, 12 CD8+ TRGs including HK2, RP2, HPSE, ELL2, GFI1, SLC22A16, FCGR3A, CTSS, SH2D1A, RBP5, ATF5, and ADAM9 were finally identified for risk model construction and validation. This model revealed a stable performance in prognostic prediction of the overall survival (OS) and event-free survival (EFS) in patients with NBL. Additionally, our research indicated that the immune and stromal scores, immune-related pathways, immune cell infiltration, the expression of major histocompatibility complex (MHC) and immune checkpoint molecules, immunotherapy response, and drug susceptibility revealed significant differences between high and low-risk groups. CONCLUSIONS: According to our analyses, the constructed CD8+ TRGs-based risk model may be promising for the clinical prediction of anti-tumor therapy responses and prognoses in NBL.

Evaluating the efficacy and cardiotoxicity of EGFR-TKI AC0010 with a novel multifunctional biosensor.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide. Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have dramatically improved the life expectancy of patients with NSCLC, concerns about TKI-induced cardiotoxicities have increased. AC0010, a novel third-generation TKI, was developed to overcome drug resistance induced by EGFR-T790M mutation. However, the cardiotoxicity of AC0010 remains unclear. To evaluate the efficacy and cardiotoxicity of AC0010, we designed a novel multifunctional biosensor by integrating microelectrodes (MEs) and interdigital electrodes (IDEs) to comprehensively evaluate cell viability, electrophysiological activity, and morphological changes (beating of cardiomyocytes). The multifunctional biosensor can monitor AC0010-induced NSCLC inhibition and cardiotoxicity in a quantitative, label-free, noninvasive, and real-time manner. AC0010 was found to significantly inhibit NCI-H1975 (EGFR-L858R/T790M mutation), while weak inhibition was found for A549 (wild-type EGFR). Negligible inhibition was found in the viabilities of HFF-1 (normal fibroblasts) and cardiomyocytes. With the multifunctional biosensor, we found that 10 µM AC0010 significantly affected the extracellular field potential (EFP) and mechanical beating of cardiomyocytes. The amplitude of EFP continuously decreased after AC0010 treatment, while the interval decreased first and then increased. We analyzed the change in the systole time (ST) and diastole time (DT) within a beating interval and found that the DT and DT/beating interval rate decreased within 1 h after AC0010 treatment. This result probably indicated that the relaxation of cardiomyocytes was insufficient, which may further aggravate the dysfunction. Here, we found that AC0010 significantly inhibited EGFR-mutant NSCLC cells and impaired cardiomyocyte function at low concentrations (10 µM). This is the first study in which the risk of AC0010-induced cardiotoxicity was evaluated. In addition, novel multifunctional biosensors can comprehensively evaluate the antitumor efficacy and cardiotoxicity of drugs and candidate compounds.

Trends in cause of death among patients with renal cell carcinoma in the United States: a SEER-based study.

BACKGROUND: Renal cell carcinoma (RCC) survival has improved due to recent developments in RCC treatment. Therefore, other co-morbid conditions may have a more critical role. This study aims to explore the common causes of death in patients with RCC to improve the management and survival of RCC. METHOD: We used the Surveillance, Epidemiology, and End Results (SEER) (1992-2018) database to get patients with RCC. We calculated the percentage of total deaths of six kinds of the cause of death (COD) and the cumulative incidence of death for each selected cause over survival time. The joinpoint regression was utilized to present the trend of mortality rate by COD. RESULTS: We enrolled 107,683 cases with RCC. RCC was the leading cause of death in patients with RCC [25376(48.3%)], followed by cardiovascular diseases [9023(17.2%)], other cancers [8003 (15.2%)], other non-cancer diseases [4195 (8%)], non-disease cause [4023 (7.7%)], and respiratory diseases [1934 (3.6%)]. The proportion of patients who died of RCC decreased gradually over survival time, and this value decreased from 69.71% in 1992-1996 to 38.96% in 2012-2018. The non-RCC cause mortality rate showed an increasing trend, whereas a slight decrease was observed in RCC specific mortality rate. The distribution of such conditions varied across different patient populations. CONCLUSION: RCC was still the primary COD of patients with RCC. However, non-RCC cause death was increasingly important among RCC patients in recent two decades. Cardiovascular disease and other cancers were crucial co-morbidities that required significant attention in the management of RCC patients.

Determination of Isoflavones in Radix puerariae from Different Origins by Ultra-High Performance Liquid Chromatography Based on Optimal Pretreatment Method.

A new method for simultaneous determination of puerarin, daidzin, daidzein and genistein in Radix puerariae by ultra-high performance liquid chromatography was established. The target analytes were extracted from Radix puerariae by 70% ethylene glycol with the assistance of ultrasonication, purified by the absorption of N-propyl ethylenediamine (PSA), and separated on a Supersil ODS column (4.6 mm × 250 mm × 2.5 µm). Gradient elution in 12 min was performed with the mobile phase 0.1% formic acid(A)-acetonitrile(B). The column temperature was 25 °C and the flow rate was 1 mL/min. The detection wavelength of the four target analytes was 250 nm. The limits of detection (LODs) of puerarin, daidzin, daidzein and genistein were 0.086 mg/L, 0.020 mg/L, 0.027 mg/L and 0.037 mg/L, respectively, and limits of quantitation (LOQs) were 0.29 mg/L, 0.065 mg/L, 0.090 mg/L and 0.12 mg/L, respectively. The recovery of the four substances ranged from 90.5% to 109.6%, and the relative standard deviation (n = 6) was less than 7.7%. With the established methods, puerarin, daidzin, daidzein and genistein in Radix puerariae from 11 origins were determined. The contents of the four compounds varied with the origin and variety. It provides basic data and technical means for quality control and regulation of Radix puerariae.

Case report: Extravascular catheter migration in a child: A rare complication of the totally implantable venous access device.

BACKGROUND: Totally implantable venous access devices (TIVADs) are widely used to gain intermittent central venous access, such as in patients who need long-term chemotherapy, total parenteral nutrition, and long-term antibiotic treatment. At present, there are many complications associated with the use of these devices. Complete extravascular migration of TIVADs via the internal jugular vein is a very rare and potentially serious condition, especially in children. CASE PRESENTATION: A 1-year-old girl needed palliative chemotherapy because of hepatoblastoma complicated by inferior vena cava thrombosis. A TIVAD was implanted through the right internal jugular vein with a routine heparin flushing tube. On the second day after the operation, a pale bloody liquid was drawn out from the device and the chest X-ray was checked to confirm that the position of the catheter was normal. On the third day after the operation, however, the patient's right respiratory sound was weakened on physical examination and auscultation. Fluoroscopy showed that the tip of the catheter was located in the right thoracic cavity, and there was a large amount of effusion in the right thoracic cavity. The pleural effusion was removed, the TIVAD was replaced again, and the child was discharged 2 days later. CONCLUSIONS: Following TIVAD implantation, if abnormalities are found, in addition to chest X-ray, saline flush and echocardiography should be performed to determine the position of the catheter and rule out extravascular migration of the catheter to avoid irreparable consequences.

Effectiveness and prognostic factors of different minimally invasive surgeries for vertebral compression fractures.

BACKGROUND: The aging of China's population has led to an increase in the incidence rate of osteoporosis, which indirectly increases the risk of OVCF in osteoporosis patients. Low back pain is the main symptom of OVCF, and severe patients can further develop kyphosis. Although the conservative treatment of OVCF can effectively control the patient's condition, long-term bed rest will increase the risk of OVCF complications. Minimally invasive surgery is a common solution for OVCF. METHODS: 100 OVCF patients admitted to our hospital from January 2021 to January 2022 are selected for analysis and randomly divided into PVP group and PKP group, 50 cases in each group. The PVP group and the PKP group undergo PVP and PKP operations respectively. The differences in efficacy indicators and adverse reactions are compared, and the multivariate Logistic regression method is used to analyze the influencing factors of postoperative secondary fractures in patients with vertebral compression fractures. RESULTS: Compared with the PVP group, the total effective rate of PKP group is significantly increased, and the VAS, ODI score, kyphotic Cobb Angle, lateral distribution rate of bone cement and bone cement leakage rate are significantly decreased (P < 0.05). Age ≥ 80 years old, female, glucocorticoid use, lateral distribution of bone cement and bone cement leakage are significantly higher in the proportion of secondary fractures and are independent risk factors for postoperative secondary fractures in patients with OVCF. CONCLUSION: PKP surgery has a higher efficacy in the treatment of OVCF patients, which can reduce the incidence of pain, adverse reactions and promote the recovery of kyphotic Cobb Angle. PKP surgery has a higher value in the treatment of OVCF. In addition, the influencing factors of secondary fracture after minimally invasive surgery in OVCF patients include age, gender, glucocorticoid use, bone cement distribution pattern, bone cement leakage, etc.

Correlation between metastatic patterns and age in patients with metastatic primary liver cancer: A population-based study.

AIM: Primary liver cancer is usually diagnosed at advanced stages with distant metastasis, underlying the high metastatic rate and mortality in patients. This study aimed to analyse the metastatic patterns and prognosis of primary liver cancer, and its relationship with age and several other factors, such as histological variants, TNM stage, and grade. METHODS: We included data from 5274 patients from the Surveillance, Epidemiology, and End Results (SEER) database of the American National Cancer Institute diagnosed with primary liver cancer with metastatic disease between 2010 and 2015. The correlation between the metastatic patterns of primary liver cancer and age was evaluated. The hazard ratio (HR) and 95% confidence intervals (CI) for overall survival were calculated by applying univariate Cox analysis, while the correlation between the metastatic patterns and age was analysed by applying multivariate Cox analysis. We also plotted Kaplan-Meier curves to illustrate the correlation between overall survival (OS) and various factors. RESULTS: Several factors were associated with poorer prognosis, including age>60 years, histologic type of spindle cell variant, higher grade, no surgery, tumour size ≥ 1 cm, and lung metastasis. The rate of metastasis increased with age. Older patients (> 50 years) were prone to bone metastasis, while less likely to have lung metastasis compared with younger patients (< 50 years). Patients with lung metastasis had a higher risk of being diagnosed with metastasis in other locations. Furthermore, surgery significantly reduced mortality and primary site surgery in particular, mitigated the risk of bone and lung metastases. CONCLUSIONS: Our study shows the correlation of prognosis and metastatic patterns with age and several other factors. The findings can hopefully provide knowledge that will allow a better diagnosis and management of elderly patients with primary liver cancer.

Multifunctional AuNPs@HRP@FeMOF immune scaffold with a fully automated saliva analyzer for oral cancer screening.

Delayed diagnosis of cancer-causing death is a worldwide concern. General diagnosis methods are invasive, time-consuming, and operation complicated, which are not suitable for preliminary screening. To address these challenges, the sensing platform based on immune scaffold and fully automated saliva analyzer (FASA) was proposed for oral cancer screening for the first time by non-invasive detection of Cyfra21-1 in saliva. Through one-step synthesis method with unique covalent and electrostatic adsorption strategy, AuNPs@HRP@FeMOF immune scaffold features multiple functions including antibody carrier, catalytic activity, and signal amplification. Highly integrated FASA with the immune scaffold provides automatic testing to avoid false-positive results and reduce pretreatment time without any user intervention. Compared with the commercial analyzer, FASA has comparable performance for Cyfra21-1 detection with a detection range of 3.1-50.0 ng/mL and R2 of 0.971, and superior features in full automation, high integration, time saving and low cost. Oral cancer patients could be distinguished accurately by the platform with an excellent correlation (R2 of 0.904) and average RSD (5.578%) without sample dilution. The proposed platform provides an effective and promising tool for cancer screening in point-of-care applications, which can be further extended for biomarker detection in universal body fluids, disease screening, prognosis review and homecare monitoring.

New taxonomic framework for Arthrodermataceae: a comprehensive analysis based on their phylogenetic reconstruction, divergence time estimation, phylogenetic split network, and phylogeography.

The Arthrodermataceae, or dermatophytes, are a major family in the Onygenales and important from a public health safety perspective. Here, based on sequenced and downloaded from GenBank sequences, the evolutionary relationships of Arthrodermataceae were comprehensively studied via phylogenetic reconstruction, divergence time estimation, phylogenetic split network, and phylogeography analysis. These results showed the clades Ctenomyces, Epidermophyton, Guarromyces, Lophophyton, Microsporum, Paraphyton, and Trichophyton were all monophyletic groups, whereas Arthroderma and Nannizzia were polyphyletic. Among them, Arthroderma includes at least four different clades, Arthroderma I, III and IV are new clades in Arthrodermataceae. Nannizzia contains at least two different clades, Nannizzia I and Nannizzia II, but Nannizzia II was a new clade in Arthrodermataceae. The unclassified group, distributed in Japan and India, was incorrectly identified; it should be a new clade in Arthrodermataceae. The phylogenetic split network based on the ITS sequences provided strong support for the true relationships among the lineages in the reconstructed phylogenetic tree. A haplotype phylogenetic network based on the ITS sequences was used to visualize species evolution and geographic lineages relationships in all genera except Trichophyton. The new framework provided here for the phylogeny and taxonomy of Arthrodermataceae will facilitate the rapid identification of species in the family, which should useful for evaluating the results of preventive measures and interventions, as well as for conducting epidemiological studies.

Predictive Value of the Log Odds of Negative Lymph Nodes/T Stage as a Novel Prognostic Factor in Bladder Cancer Patients After Radical Cystectomy.

Background: The effect of lymph node resection on the prognosis of bladder cancer (BLCA) patients receiving radical cystectomy should not be ignored. Our aim was to explore the prognostic value of the log odds of negative lymph nodes/T stage (LONT) and construct a more effective nomogram based on LONT to predict cancer-specific survival (CSS) in postoperative BLCA patients. Methods: Patients diagnosed with BLCA after radical cystectomy between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled. We randomly split (7:3) these patients into the primary cohort and internal validation cohort. 86 patients from the First Affiliated Hospital of Nanchang University were collected as the external validation set. Univariate and multivariate cox regression analyses were carried out to seek prognostic factors of postoperative BLCA patients. According to these significantly prognostic factors, a simple-to-use nomogram was established for predicting CSS. Their performances were evaluated by using calibration curves, the concordance index (C-index), the receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). In addition, different risk groups were tested by Kaplan-Meier curves and log-rank tests. Result: Whether in cancer-specific survival (CSS) or overall survival (OS), LONT was an independent and significant prognostic factor. Through further screening, the ultimate nomogram of CSS was composed of nine independent prognostic factors including LONT, age, race, tumor size, histologic type, T stage, N stage, summary stage and chemotherapy. The C-index of nomogram in the primary cohort, internal and external validation cohort were 0.734, 0.720 and 0.728, respectively. The AUC of predicting CSS at 3 and 5 years were 0.783 and 0.774 in the primary cohort and 0.781 and 0.781 in the validation cohort. The results of calibration and DCA showed good concordance and clinical applicability. Significant differences (P < 0.05) were displayed in CSS among different risk groups. Conclusion: LONT was regarded as a novel and reliable prognostic factor. Compared with the AJCC staging system, the established nomogram based on LONT can more effectively predict the prognosis of BLCA patients after radical cystectomy.

Vitamin D Receptor Genetic Polymorphisms Associate With a Decreased Susceptibility to Extremity Osteomyelitis Partly by Inhibiting Macrophage Apoptosis Through Inhibition of Excessive ROS Production via VDR-Bmi1 Signaling.

Background: Previous studies had reported that vitamin D receptor (VDR) gene polymorphisms were related to the development of several inflammatory disorders. However, potential links between such variations and the risk of developing a bone infection and underlying mechanisms remain unclear. This study aimed to analyze potential associations between VDR genetic variations and susceptibility to extremity osteomyelitis (OM) in a Chinese Han population and investigate potential mechanisms. Methods: Between January 2016 and August 2020, altogether 398 OM patients and 368 healthy controls were genotyped for six VDR gene polymorphisms, including ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), TaqI (rs731236), GATA (rs4516035), and Cdx-2 (rs11568820) by the SNaPshot genotyping method. Then, male C57BL/6 mice were randomly divided into vitamin D-standard, -excess, -deficient, and -rescued groups. One week after making the model surgery, OM occurrence and severity were assessed using the bacterial count and histopathological staining. In vitro, phagocytosis, apoptosis, and bactericidal ability of macrophages were evaluated by overexpression or knockdown of VDR protein. Results: Significant associations were found among rs7975232, rs1544410, and OM development by the recessive model (AA vs. AC + CC, p = 0.037, OR = 0.594), homozygous model (AA vs. CC, p = 0.033, OR = 0.575), and heterozygous model (CT vs. CC, p = 0.049, OR = 0.610), respectively. Patients with the AA genotype of rs7975232 had a relatively higher mean level of vitamin D than those with AC and CC genotypes (22.5 vs. 20.7 vs. 19.0 ng/ml). Similarly, patients with CT genotype of rs1544410 had a relatively higher mean vitamin D level than those with CC genotype (20.94 vs. 19.89 ng/ml). Outcomes of in vivo experiments showed that the femoral bacterial load of vitamin D-deficient mice was highest among different vitamin D dose groups, with the most severe histopathological features of infection, and vitamin D supplementation partly reversed the changes. While in vitro experiment results revealed that active vitamin D promoted phagocytosis and sterilization of macrophages and inhibited apoptosis during infection. Reactive oxygen species (ROS) inhibitor inhibited apoptosis of macrophages induced by bacterial infection. Active vitamin D inhibited excessive ROS production in macrophages via the VDR-Bmi1 signaling pathway. Conclusion: In this Chinese cohort, ApaI and BsmI are associated with a decreased risk of OM development by influencing serological vitamin D level, the latter of which reduced macrophage apoptosis with inhibition of excessive ROS production via the VDR-Bmi1 signaling pathway.

FOXA1 of regulatory variant associated with risk of breast cancer through allele-specific enhancer in the Chinese population.

BACKGROUND: FOXA1 is a pioneer transcription factor which has been established as a carcinogenic factor and can regulate the expression of downstream target genes in breast cancer. We hypothesized that genetic variants modulating FOXA1 expression might play a role in the risk of breast cancer. METHODS: Physical interaction predicted by PreSTIGE analysis and CHIA-PET data integration with cis-expression quantitative trait loci (cis-eQTL) based SNP-FOXA1 analysis were used to identify potentially regulatory variants modulating the expression of FOXA1. Then, we utilized a case-control study consisting of 855 new diagnosed breast cancer cases and 920 controls in the Chinese population to identify breast cancer associated variants. Biological assays were conducted in breast cancer cell lines to illustrate the effects of associated variants on breast cancer risk. RESULTS: We identified that rs7160774 G > A variant was associated with lower risk of breast cancer (OR = 0.77, 95% confidence interval = 0.62-0.96, P = 0.022). Biological experiments indicated that rs7160774[A] allele down-regulated the expression of FOXA1 compared to the G allele by influencing transcription factor binding affinity, thus playing an important role in the development of breast cancer. CONCLUSION: Our study suggested that the regulatory variant rs7160774 was associated with risk of breast cancer by long-range modulating FOXA1 expression and provided critical insights into pinpoint causal genetic variants.

Urinary bisphenol A and its interaction with CYP17A1 rs743572 are associated with breast cancer risk.

OBJECTIVE: Bisphenol A (BPA), a common endocrine disrupter, can be activated by cytochrome P450 (CYP) metabolizing enzymes and might influence the development of breast cancer (BC). We hypothesized that BPA could interact with CYP genes, synergistically contributing to the BC risk. METHODS: Urinary BPA was measured in a total of 302 newly diagnosed BC patients and 302 healthy controls by ultra-high performance liquid chromatography-high resolution mass spectrometry. A set of seven CYP gene polymorphisms was genotyped by using the Sequenom MassARRAY system. A multivariate logistic regression model was used to assess the associations of BPA and BPA-SNP interaction with BC risk. RESULTS: BC patients had a higher urinary BPA concentration than healthy individuals (P < 0.001). Each 1-unit increase in log-transformed urinary BPA was associated with a 54 % increased BC risk [95 % confidence interval (CI), 1.34-1.77, P < 0.001]. Individuals with the CYP19A1 rs1902580 GA + AA genotype showed a significantly higher BC risk than those with the GG genotype (OR = 1.45, 95 % CI, 1.01-2.09, P < 0.05). A significant BPA-CYP17A1 rs743572 interaction was found to be associated with a higher risk of BC (Pinteraction = 0.020). Compared with low-BPA individuals carrying CYP17A1 rs743572 GG genotypes, high-BPA individuals with the GA + AA genotype had a higher BC risk, with an odds ratio of 2.49 (95 % CI, 1.52-4.13, P < 0.05). CONCLUSIONS: The positive association of BPA exposure with BC risk might be modified by CYP17A1 rs743572, providing evidence for the interaction effect of environment-genes on the etiology of BC.