[Treatment response of a two-dose regimen of dose-adjusted inotuzumab ozogamicin in relapsed/refractory B-cell acute lymphoblastic leukemia].

Objective: To observe the treatment response of a two-dose regimen of inotuzumab ozogamicin (inotuzumab), a monoclonal antibody targeting CD22, for patients with heavily treated relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), including those failed or relapsed after chimeric antigen receptor (CAR) -T-cell therapy. Methods: Pediatric and adult patients who received two doses of inotuzumab and who were evaluated after inotuzumab treatment were included. Antibody infusions were performed between March 2020 and September 2022. All patients expressed CD22 antigen as detected by flow cytometry (>80% leukemic cells displaying CD22) before treatment. For adults, the maximum dosage per administration was 1 mg (with a total of two administrations). For children, the maximum dosage per administration was 0.85 mg/m(2) (no more than 1 mg/dose; total of two administrations). The total dosage administered to each patient was less than the standard dosage of 1.8 mg/m(2). Results: Twenty-one patients with R/R B-ALL were included, including five children (<18 years old) and sixteen adults. Seventeen patients presented with 5.0% -99.0% leukemic blasts in the bone marrow/peripheral blood or with extramedullary disease, and four patients were minimal residual disease (MRD) -positive. Fourteen patients underwent both CD19 and CD22 CAR-T-cell therapy, four underwent CD19 CAR-T-cell therapy, and three underwent blinatumomab therapy. Eleven patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). After inotuzumab treatment, 14 of 21 patients (66.7% ) achieved a complete response (CR, one was MRD-positive CR), and all four MRD-positive patients turned MRD-negative. Four of six patients who failed recent CD22 CAR-T-cell therapy achieved a CR after subsequent inotuzumab treatment. Seven patients (33.3% ) demonstrated no response. Grade 1-3 hepatotoxicity occurred in five patients (23.8% ), one child with no response experienced hepatic veno-occlusive disease (HVOD) during salvage transplantation and recovered completely. Conclusion: For patients with heavily treated R/R B-ALL, including those who had undergone allo-HSCT and CD19/CD22 CAR-T-cell therapy, the two-dose regimen of inotuzumab resulted in a CR rate of 66.7%, and the frequency of hepatotoxicity and HVOD was low.

Infection risk in psoriatic patients receiving tumour necrosis factor inhibitors: a 20-year systematic review and meta-analysis of randomized controlled trials.

Tumour necrosis factor inhibitors (TNFis) are commonly used for treating psoriatic diseases; however, the risk of infection while receiving TNFis remains uncertain. The aim of this study was to investigate the infection risk in patients with psoriatic disease receiving TNFis. A prospectively registered systematic literature search was conducted in Medline (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and the ClinicalTrials.gov databases from inception to December 31, 2021. We included double-blind randomized controlled trials that compared TNFis or other biologics with placebo in adults with psoriasis or psoriatic arthritis. The primary outcomes included overall and serious infection risks, and secondary outcomes included upper respiratory infections and nasopharyngitis risks. The risk ratio of the dichotomous outcome was calculated using the Mantel-Haenszel method with random effects, and heterogeneity was assessed using Cochran's Q statistic and quantified using the I-squared statistic. A total of 48 studies with 15 464 patients with psoriatic diseases were included. The meta-analysis demonstrated a slightly increased overall infection risk (risk ratio = 1.09; 95% confidence interval, 1.02-1.15) but not serious infection risk (risk ratio = 0.95; 95% confidence interval, 0.61-1.49) among patients receiving TNFis. There were also no increased risks of upper respiratory infections (risk ratio = 1.10; 95% confidence interval, 0.94-1.28) or nasopharyngitis (risk ratio = 1.14; 95% confidence interval, 1.00-1.30). In subgroup analyses using the fixed effects model, only etanercept and certolizumab pegol were, respectively, associated with an increased risk of overall infection (RR = 1.14, 95% CI, 1.03-1.27) and upper respiratory infections (RR = 1.42, 95% CI, 1.02-1.98). In conclusion, evidence to date suggests an increased overall infection risk that is generally tolerable in patients with psoriatic diseases receiving TNFis. There are no increased risks of serious infections, upper respiratory infections or nasopharyngitis.

Application of point-of-care ultrasound in patients receiving enteral nutrition.

OBJECTIVE: Enteral nutrition (EN) is the first-choice nutritional support, as it is more in line with normal physiological processes. During EN, the major goals to achieve include accurate confirmation of the feeding tube position, monitoring the gastric residual volume, assessing gastrointestinal motility, and monitoring the nutritional status of patients. With rapid development in technology, point-of-care ultrasound (POCUS) has become a more convenient and effective technical tool for monitoring critically ill patients receiving EN. In this review, we have summarized and discussed the value of POCUS in the implementation, monitoring, and evaluation of EN therapy to provide a reference for nutritional support of critically ill patients in critical care settings. MATERIALS AND METHODS: This is a narrative review. A literature search for Scopus-indexed articles was performed randomly using PubMed and MEDLINE databases as the primary sources. No specific term was used for the search. RESULTS: POCUS can be used for positioning of nasogastric and nasointestinal tubes, evaluation of gastric residuals and gastrointestinal motility as well as monitoring of nutritional status. CONCLUSIONS: POCUS is a real-time, highly repeatable, radiation-free, and non-invasive visual inspection technique, with high application value in assessing the nutritional status of patients receiving EN and guiding the development of further nutritional treatment plans. It is an important diagnostic and monitoring tool that can be used by the clinicians in the ICU.

Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance.

Resulting from impaired collagen turnover, fibrosis is a hallmark of adipose tissue (AT) dysfunction and obesity-associated insulin resistance (IR). Prolidase, also known as peptidase D (PEPD), plays a vital role in collagen turnover by degrading proline-containing dipeptides but its specific functional relevance in AT is unknown. Here we show that in human and mouse obesity, PEPD expression and activity decrease in AT, and PEPD is released into the systemic circulation, which promotes fibrosis and AT IR. Loss of the enzymatic function of PEPD by genetic ablation or pharmacological inhibition causes AT fibrosis in mice. In addition to its intracellular enzymatic role, secreted extracellular PEPD protein enhances macrophage and adipocyte fibro-inflammatory responses via EGFR signalling, thereby promoting AT fibrosis and IR. We further show that decreased prolidase activity is coupled with increased systemic levels of PEPD that act as a pathogenic trigger of AT fibrosis and IR. Thus, PEPD produced by macrophages might serve as a biomarker of AT fibro-inflammation and could represent a therapeutic target for AT fibrosis and obesity-associated IR and type 2 diabetes.

Lymphoepithelial carcinoma in the sublingual gland.

Lymphoepithelial carcinoma is rare in the salivary glands, with an incidence of 0.4%. The most commonly affected site is the parotid gland, followed by the submandibular gland. Lymphoepithelial carcinoma in the sublingual gland has been reported only four times in the existing English-language literature. Such tumours are characterized by the presence of a poorly differentiated carcinoma that is surrounded and infiltrated by lymphocytes, and they are strongly associated with Epstein-Barr virus infection, patient ethnicity, and prominent radiosensitivity. Wide surgical excision combined with adjuvant therapy has been suggested as the first-choice therapeutic regimen. This report describes the case of a 34-year-old Indonesian woman who was evaluated and treated in Taipei Medical University Hospital. She had a tumour that presented as a painless swelling on the floor of the mouth. The diagnosis was confirmed by conducting an incisional biopsy, and a wide surgical excision with bilateral supraomohyoid neck dissection and free flap reconstruction was performed. The patient also underwent adjuvant chemoradiotherapy. No evidence of local recurrence or distant metastasis was detected during the 6 months of follow-up. Subsequently, the patient returned to her home country, and further follow-ups were not conducted.

[Association between platelet parameters and risk for stroke in people with different blood pressure levels: Dongfeng-Tongji cohort].

Objective: To explore the associations of platelet parameters platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) with the risk for stroke in people with different blood pressure levels. Methods: All the participants were from Dongfeng-Tongji cohort, including 38 295 retired employees from Dongfeng Motor Corporation at the first follow-up survey. After excluding participants with coronary heart disease, stroke, cancer, history of platelet influential drug use and those with missed data of platelet parameters or blood pressure or lost to follow-up, finally a total of 21 294 participants were included in this study. All the participants completed baseline questionnaires, physical examinations, clinical biochemical tests, and blood sample collection. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and the corresponding 95% confident intervals (CIs) for the associations between platelet parameters and risk for stroke in people with different blood pressure levels. Results: After a mean follow-up of 8.0 years, 1 578 participants developed incident stroke [1 266 ischemic stroke (IS) cases and 312 hemorrhagic stroke (HS) cases]. Compared with the participants with PLT<188×109/L, those with PLT≥188×109/L among hypertension cases were significantly associated with higher risks for stroke and IS (stroke: HR=1.27, 95%CI: 1.12-1.44; IS: HR=1.39, 95%CI: 1.21-1.60). Among hypertension group, compared with participants with PCT<0.165%, PCT≥0.165% were significantly associated with higher risk for stroke (HR=1.15, 95%CI: 1.01-1.30) and lower risk for HS (HR=0.70, 95%CI: 0.53-0.93); Among non-hypertension and hypertension group, PCT ≥0.165% were significantly associated with higher risks of IS (HR=1.27, 95%CI: 1.05-1.54; HR=1.31, 95%CI: 1.14-1.50). MPV and PDW were not significantly associated with risk for stroke. Risk for stroke increased significantly in hypertension cases with different platelet parameters levels compared with non-hypertension cases with lower levels of each platelet parameters. Conclusion: Higher levels of PLT and PCT could increase the risks for stroke and IS in middle-aged and elderly hypertension patients, and lower levels of PCT could decrease the risk for HS in hypertension patients.

Modified endoscopic medial maxillectomy for a mixed maxillary inverted papilloma and mycetoma with absent prelacrimal recess.

Endoscopic prelacrimal recess approach is a promising technique for treating various maxillary sinus diseases because it allows for adequate visualization and wide access to the entire maxillary sinus. However, the incidence of absent prelacrimal recess (PLR) has ranged from 7% to 17.5%, implying that there is a limitation for the application of EPLA in this population. Here, a male patient with concomitant Krouse T2 maxillary inverted papilloma and mycetoma presenting with unilateral nasal obstruction and blood-tinged secretion is described. The presurgical computed tomography showed no recess. By dislocating the nasolacrimal duct from the bony canal and removing the medial maxillary wall sufficiently to extend the surgical corridor; and by preserving the inferior turbinate, nasal mucosa, and nasolacrimal duct, the patient did not experience any postoperative complications. In conclusion, our modified technique may be an effective and safe strategy for treating maxillary sinus disease without prelacrimal recess.

Understanding the Early Biological Effects of Isoprene-Derived Particulate Matter Enhanced by Anthropogenic Pollutants.

INTRODUCTION: Airborne fine particulate matter (PM2.5; particulate matter ≤ 2.5 µm in aerodynamic diameter) plays a key role in air quality, climate, and public health. Globally, the largest mass fraction of PM2.5 is organic, dominated by secondary organic aerosol (SOA) formed from atmospheric oxidation of volatile organic compounds (VOCs). Isoprene from vegetation is the most abundant nonmethane VOC emitted into Earth's atmosphere. Isoprene has been recently recognized as one of the major sources of global SOA production that is enhanced by the presence of anthropogenic pollutants, such as acidic sulfate derived from sulfur dioxide (SO2), through multiphase chemistry of its oxidation products. Considering the abundance of isoprene-derived SOA in the atmosphere, understanding mechanisms of adverse health effects through inhalation exposure is critical to mitigating its potential impact on public health. Although previous studies have examined the toxicological effects of certain isoprene-derived gas-phase oxidation products, to date, no systematic studies have examined the potential toxicological effects of isoprene-derived SOA, its constituents, or its SOA precursors on human lung cells. SPECIFIC AIMS: The overall objective of this study was to investigate the early biological effects of isoprene-derived SOA and its subtypes on BEAS-2B cells (a human bronchial epithelial cell line), with a particular focus on the alteration of oxidative stress- and inflammation-related genes. To achieve this objective, there were two specific aims.1. Examine toxicity and early biological effects of SOA derived from the photochemical oxidation of isoprene, considering both urban and downwind-urban types of chemistry.2. Examine toxicity and early biological effects of SOA derived directly from downstream oxidation products of isoprene (i.e., epoxides and hydroperoxides). METHODS: Isoprene-derived SOA was first generated by photooxidation of isoprene under natural sunlight in the presence of nitric oxide (NO) and acidified sulfate aerosols. Experiments were conducted in a 120-m3 outdoor Teflon-film chamber located on the roof of the Gillings School of Global Public Health, University of North Carolina at Chapel Hill (UNC-Chapel Hill). BEAS-2B cells were exposed to chamber- generated isoprene-derived SOA using the Electrostatic Aerosol in Vitro Exposure System (EAVES). This approach allowed us to generate atmospherically relevant compositions of isoprene-derived SOA and to examine its toxicity through in vitro exposures at an air-liquid interface, providing a more biologically relevant exposure model. Isoprene-derived SOA samples were also collected, concurrently with EAVES sampling, onto Teflon membrane filters for in vitro resuspension exposures and for analysis of aerosol chemical composition by gas chromatography/electron ionization-quadrupole mass spectrometry (GC/EI-MS) with prior trimethylsilylation and ultra-performance liquid-chromatography coupled to high-resolution quadrupole time-of-flight mass spectrometry equipped with electrospray ionization (UPLC/ESI-HR-QTOFMS). Isoprene-derived SOA samples were also analyzed by the dithiothreitol (DTT) assay in order to characterize their reactive oxygen species (ROS)-generation potential.Organic synthesis of known isoprene-derived SOA precursors, which included isoprene epoxydiols (IEPOX), methacrylic acid epoxide (MAE), and isoprene-derived hydroxyhydroperoxides (ISOPOOH), was conducted in order to isolate major isoprene-derived SOA formation pathways from each other and to determine which of these pathways (or SOA types) is potentially more toxic. Since IEPOX and MAE produce SOA through multiphase chemistry onto acidic sulfate aerosol, dark reactive uptake experiments of IEPOX and MAE in the presence of acidic sulfate aerosol were performed in a 10-m3 flexible Teflon indoor chamber at UNC-Chapel Hill. Since the generation of SOA from ISOPOOH (through a non-IEPOX route) requires a hydroxyl radical (•OH)-initiated oxidation, ozonolysis of tetramethylethylene (TME) was used to form the needed •OH radicals in the indoor chamber. The resultant low-volatility multifunctional hydroperoxides condensed onto nonacidified sulfate aerosol, yielding the ISOPOOH-derived SOA needed for exposures. Similar to the outdoor chamber SOAs, IEPOX, MAE- and ISOPOOH-derived SOAs were collected onto Teflon membrane filters and were subsequently chemically characterized by GC/EI-MS and UPLC/ESI-HR-QTOFMS as well as for ROS-generation potential using the DTT assay. These filters were also used for resuspension in vitro exposures.By conducting gene expression profiling, we provided mechanistic insights into the potential health effects of isoprene-derived SOA. First, gene expression profiling of 84 oxidative stress- and 249 inflammation-associated human genes was performed for cells exposed to isoprene-derived SOA generated in our outdoor chamber experiments in EAVES or by resuspension. Two pathway-focused panels were utilized for this purpose: (1) nCounter GX Human Inflammation Kit comprised of 249 human genes (NanoString), and (2) Human Oxidative Stress Plus RT2 Profiler PCR Array (Qiagen) comprised of 84 oxidative stress-associated genes. We compared the gene expression levels in cells exposed to SOA generated in an outdoor chamber from photochemical oxidation of isoprene in the presence of NO and acidified sulfate seed aerosol to cells exposed to a dark control mixture of isoprene, NO, and acidified sulfate seed aerosol to isolate the effects of the isoprene-derived SOA on the cells using the EAVES and resuspension exposure methods. Pathway-based analysis was performed for significantly altered genes using the ConsensusPathDB database, which is a database system for the integration of human gene functional interactions to provide biological pathway information for a gene set of interest. Pathway annotation was performed to provide biological pathway information for each gene set. The gene-gene interaction networks were constructed and visualized using the GeneMANIA Cytoscape app (version 3.4.1) to predict the putative function of altered genes. Lastly, isoprene-derived SOA collected onto filters was used in resuspension exposures to measure select inflammatory biomarkers, including interleukin 8 (IL-8) and prostaglandin-endoperoxide synthase 2 (PTGS2) genes, in BEAS-2B cells to ensure that effects observed from EAVES exposures were attributable to particle-phase organic products. Since EAVES and resuspension exposures compared well, gene expression profiling for IEPOX-, MAE- and ISOPOOH-derived SOA were conducted using only resuspension exposures. RESULTS AND CONCLUSIONS: Chemical characterization coupled with biological analyses show that atmospherically relevant compositions of isoprene-derived SOA alter the levels of 41 oxidative stress-related genes. Of the different composition types of isoprene-derived SOA, MAE- and ISOPOOH-derived SOA altered the greatest number of genes, suggesting that carbonyl and hydroperoxide functional groups are oxidative stress promoters. Taken together, the different composition types accounted for 34 of the genes altered by the total isoprene-derived SOA mixture, while 7 remained unique to the total mixture exposures, indicating that there is either a synergistic effect of the different isoprene-derived SOA components or an unaccounted component in the mixture.The high-oxides of nitrogen (NOx) regime, which yielded MAE- and methacrolein (MACR)-derived SOA, had a higher ROS-generation potential (as measured by the DTT assay) than the low- NOx regime, which included IEPOX- and isoprene-derived SOA. However, ISOPOOH-derived SOA, which also formed in the low- NOx regime, had the highest ROS-generation potential, similar to 1,4-naphthoquinone (1,4-NQ). This suggests that aerosol-phase organic peroxides contribute significantly to particulate matter (PM) oxidative potential. MAE- and MACR- derived SOA showed equal or greater ROS-generation potential than was reported in prior UNC-Chapel Hill studies on diesel exhaust PM, highlighting the importance of a comprehensive investigation of the toxicity of isoprene-derived SOA. Notably, ISOPOOH-derived SOA was one order of magnitude higher in ROS-generation potential than diesel exhaust particles previously examined at UNC-Chapel Hill. As an acellular assay, the DTT assay may not be predictive of oxidative stress; therefore, we also focused on the gene expression results from the cellular exposures.We have demonstrated that the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and the redox-sensitive activation protein-1 (AP-1) transcription factor networks have been significantly altered upon exposure to isoprene-derived SOA. The identification of Nrf2 pathway in cells exposed to isoprene-derived SOA is in accordance with our findings using the DTT assay, which measures the thiol reactivity of PM samples as a surrogate for their ROS-generation potential. Specifically, our results point to the cysteine-thiol modifications within cells that lead to activation of Nrf2-related gene expression.However, based on our gene expression results showing no clear relationship between DTT activity and the number of altered oxidative stress-related genes, the DTT activity of isoprene-derived SOA may not be directly indicative of toxicity relative to other SOA types. While activation of Nrf2-associated genes has been identified with responses to oxidative stress and linked to traffic related air pollution exposure in both toxicological and epidemiological studies, their implicit involvement in this study suggests that activation of Nrf2-related gene expression may occur with exposures to all sorts of PM types.By controlling the exposure time, method, and dose we demonstrated that among the SOA derived from previously identified individual precursors of isoprene-derived SOA, ISOPOOH-derived SOA alters more oxidative stress related genes than does IEPOX-derived SOA, but fewer than MAE-derived SOA. This suggests that the composition of MAE-derived SOA may be the greatest contributor to alterations of oxidative stress-related gene expression observed due to isoprene-derived SOA exposure. Further study on induced levels of protein expression and specific toxicological endpoints is necessary to determine if the observed gene expression changes lead to adverse health effects. In addition, such studies have implications for pollution-control strategies because NOx and SO2 are controllable pollutants that can alter the composition of SOA, and in turn alter its effects on gene expression. The mass fraction of different components of atmospheric isoprene derived SOA should be considered, but altering the fraction of high- NOx isoprene-derived SOA (e.g., MAE derived SOA) may yield greater changes in gene expression than altering the fraction of low- NOx isoprene derived SOA types (ISOPOOH- or IEPOX-derived SOA). Finally, this study confirms that total isoprene-derived SOA alters the expression of a greater number of genes than does SOA derived from the tested precursors. This warrants further work to determine the underlying explanation for this observation, which may be uncharacterized components of isoprene-derived SOA or the potential for synergism between the studied components.

[Prospective controlled observation ofeffect of adjuvant chemotherapy onsurvival and prognosis ofhigh-risk upper tract urothelial carcinoma patients underwent radical nephroureterectomy].

Objective: To assess the oncologic outcomes of radical nephroureterectomy (RNU) combined with adjuvant chemotherapy (ACT) in patients with high risk upper tract urothelial carcinoma (UTUC). Methods: From January 2014, all high-risk UTUC patients after RNU surgery were enrolled in this prospective comparative trial. And these patients were randomized to ACT group (Gemcitabine+Cisplatin three weeks regimen) and observing group. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine overall survival (OS), cancer specific survival (CSS) and disease-free survival (PFS) in the cohort. Results: The median follow-up duration was36 months (range: 6-54) in the ACT group (n=94) and 30 months (range: 6-54) in the observing group (n=82). Oncologic outcomes of RNU treated high-risk UTUC patients were improved much significantly by ACT: OS [P=0.0397, HR: 1.39(0.91-1.75)], CSS [P=0.0255, HR: 1.26(1.07-1.45)] and PFS [P=0.0033, HR: 3.78(3.13-4.55)]. The further analysis in lymph node positive cohort displayed that median times of oncologic events were prolonged in the ACT group compared with the observing group: OS (26.8mon vs 36.3mon, P=0.0255), CSS (28.2mon vs39.3mon, P=0.0197) and PFS (11.4mon vs 31.9mon, P=0.0018). Additionally in T3/4 cohort, the significant growth in the median times of OS (20.6mon vs 32.2mon, P=0.0183), CSS (21.9mon vs 38.4mon, P=0.0226) and PFS (13.9mon vs 36.3mon, P=0.0217) were observed in ACT group. Conclusion: ACT could play the important synergistic role in improving the OS, CSS and PFS of high-risk UTUC patients after RNU.

Photoinduced antibacterial activity of NRC03 peptide-conjugated dopamine/nano-reduced graphene oxide against Staphylococcus aureus.

In recent years, several drugs have become relatively easy to obtain with the rapid development of the economy and improvement in people's living standards. However, pathogenic bacteria have evolved strains that are resistant to certain drugs, such as antibiotics. Peptides are generally considered to be safe, have high tolerance to drugs, and are easy to manufacture. However, peptides are easily decomposed in complex biological environments. To solve this problem, many studies have modified peptides on the surface of nanomaterials to increase their functionality, biocompatibility, and stability. Meanwhile, nanomaterials have exhibited good absorption of near-infrared (NIR) light. When the NIR laser is focused on nanomaterials, photons are absorbed and the energy of the photons is converted into heat. Low-toxicity NRC03 peptide-conjugated dopamine/nano-reduced-graphene oxide (NRC03-DA/nRGO) nanomaterials are synthesized in this study for antibacterial testing using photothermal technology. The strains used in this study were Gram-positive Staphylococcus aureus (S. aureus). Our results indicated that the synthesized NRC03-DA/nRGO exhibits good absorption of NIR light and high photothermal conversion efficiency. Moreover, the synthesized NRC03-DA/nRGO inhibits the growth and survival of S. aureus. When the NRC03 peptide is modified on the surface of DA/nRGO, its biological stability is improved and the photothermal effect generated by NIR light produces additive effects, thereby indicating potential antibacterial applications.

[Derepression of CXCR7 indicates resistance to enzalutamide in castration resistant prostate cancer].

Objective: To investigate the effect of the derepression of chemokine receptor-7 (CXCR7) in prostatic tissues from patients with Castration Resistant Prostate Cancer (CRPC) on the resistance to enzalutamide (Enza). Methods: During the period of January 2015 to December 2017 all CRPC cases who underwent radical radiotherapy or androgen deprivation therapy (ADT) were evaluated. After prostatic puncture biopsy, the tissues were treated for immunostaining with CXCR7. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine PSA Progression-Free Survival (PSAP-FS) and Clinical or Radiographic Progression-Free Survival (CRP-FS) in the cohort. At last, PSA response rates and progression outcomes in CXCR7 negative cases and CXCR7 positive cases were analyzed. Results: Total 39 CRPC patients were enrolled in this study. And 23 cases derepress CXCR7, 16 cases negatively express CXCR7. The median follow-up duration was 12 months (range: 6-18) in the cohort. Chi-square analysis confirmed that PSA response rates after Enza treatment were significantly associated with CXCR7 derepression (χ(2)=22.129, P=0.000 06). Compared with CXCR7 positive expression group, CXCR7 negative expression group displayed improved median PSAP-FS (4.4 mon vs 11.7 mon, P=0.040 8) and CRP-FS (5.2 mon vs 13.1 mon, P=0.036 2) after Enza treatment. Conclusion: Derepression of CXCR7 in CRPC patients may be associated with resistance to enzalutamide. This protein may be novel target for treatment of CRPC.

[Correlation between interleukin-6 single nucleotide polymorphism and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure].

Objective: To investigate the correlation between interleukin-6 (IL-6) single nucleotide polymorphism (SNP) and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods: Patients with chronic hepatic diseases diagnosed as HBV infection in the Hepatology Center of the First Affiliated Hospital of Fujian Medical University from July 2012 to March 2018 were divided into HBV-ACLF and non-ACLF group. SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) was determined by the improved multi-temperature ligase detection reaction (imLDRTM) technique. Simultaneously, case data were reviewed with the 3-months followed up survival condition of the ACLF group. Normally distributed data were expressed as arithmetic means and SDs, and t-test was adopted. Data with skewed distribution were expressed as medians with interquartile range, and were measured by non-parametric test. Multivariate logistic regression analysis was used to analyze the relative risk of genetic polymorphism and HBV-ACLF as well as the relationship between IL-6 SNPs with the occurrence and prognosis of HBV-ACLF. Results: Four hundred patients were included in the study, with 122 (30.5%) in the HBV-ACLF and 278 (69.5%) in the non-ACLF group. There were significant differences in total bilirubin, albumin, and white blood cell count, percentage of neutrophils, platelet count, alanine aminotransferase, aspartate aminotransferase, prothrombin time and international standardized ratio, creatinine and the model for end-stage liver disease score between the two groups (P < 0.001). The genotype of IL-6 genes (rs1800795, rs1800797, rs2069827, and rs2069830) of all subjects showed no mutation or the mutation rate under 1%. There was no significant difference in the genotype of IL-6 (rs1524107, rs2069837, rs2069840 and rs2069845) between the two groups (P > 0.05). Multivariate logistic regression analysis showed that the SNPs in the above four loci of IL-6 gene was not associated with HBV-ACLF risk, nor had significant correlation with the 3-months prognosis. Conclusion: The SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) is unrelated to the occurrence and short-term prognosis of HBV-ACLF.

Assessing Vascularity of Osseous Spinal Metastases with Dual-Energy CT-DSA: A Pilot Study Compared with Catheter Angiography.

BACKGROUND AND PURPOSE: Spine debulking surgery in patients with hypervascular spinal metastasis is associated with massive intraoperative blood loss, but currently, the vascularity of tumor is determined by invasive conventional angiography or dynamic contrast MR imaging. We aimed to investigate the usefulness of noninvasive dual-energy CT-DSA, comparing it with conventional angiography in evaluating the vascularity of spinal metastasis. MATERIALS AND METHODS: We conducted a retrospective study from January to December 2018. A total of 15 patients with spinal metastasis undergoing dual-energy CT, conventional DSA, and subsequent debulking surgery were included. CT-DSA images were produced after rigid-body registration and subtraction between CT phases. Qualitative and quantitative assessments of tumor vascularity were conducted. Correlations between CT-DSA and conventional DSA results were evaluated using the Spearman coefficient. The mean enhancement in the estimated tumor volume and surgical blood loss was compared between hypervascular and nonhypervascular groups using the Wilcoxon rank sum test. RESULTS: The CT-DSA and DSA results were strongly correlated, with ρ = 0.87 (P < .001). The DSA and the quantitative enhancement index also showed a strong correlation with ρ = 0.83 (P < .001). Wilcoxon rank sum testing between hypervascular and nonhypervascular CT-DSA groups showed a difference in enhancement indices (P = .0003). The blood loss between the hypervascular and nonhypervascular groups was nonsignificant (P = .09). CONCLUSIONS: Dual-energy CT-DSA correlates well with conventional DSA in assessing the vascularity of spinal metastasis. It may serve as a noninvasive preoperative evaluation option before debulking surgery.

[Oncologic outcomes of high-risk upper tract urothelial carcinoma patients undergoing radical nephroureterectomy combined with adjuvant chemotherapy].

Objective: To assess the oncologic outcomes of radical nephroureterectomy (RUN) combined with adjuvant chemotherapy (ACT) in patients with high risk upper tract urothelial carcinoma (UTUC). Methods: One-hundred-thirty-four individuals with high-risk UTUC who underwent RUN with or without ACT were evaluated. Cox proportional hazard model and Kaplan-Meier analysis were used to determine overall and cancer specific survival in the cohort. Results: The median follow-up duration was 24 months (range: 6-36) in the RUN group (n=61) and 18 months (range: 6-36) in the RUN+ACT group (n=73). Median time of overall survival (OS) and cancer specific survival (CSS) showed much better in RUN+ACT group than in RUN group, but the differences were not reached the significant standard. The further analysis in lymph node positive cohort displayed that median times of oncologic events were prolonged in the RUN+ACT group compared with the RUN group: OS (30.1 mon vs 18.0 mon, P=0.083) and CSS (29.2 mon vs 18.6 mon, P=0.047). Additionally in T3/T4 cohort, the significant growth in the median times of OS (25.2 mon vs 12.6 mon, P=0.038) and CSS (31.3 mon vs 18.9 mon, P=0.044) were observed in combination treatment group. Conclusion: ACT could play the important synergistic role in improving the OS and CSS of RUN treated UTUC patients with lymph node-positive or stage of T3/T4.

[Activation of HIF-1α/ß-catenin signal pathway leads to radioresistance of prostate cancer cells].

Objective: To investigate the role of hypoxia-inducible factor-1α (HIF-1α) and ß-catenin in radioresistance of prostate cancer (PCa) cells. Method: Two PCa cell lines, LNCaP and C4-2B, were grouped as: negative control (no treatment), HIF-1α overexpression group (transfected with HIF-1α plasmids), and ß-catenin silencing group (transfected with HIF-1α plasmids and ß-catenin-shRNA). Cell proliferation, cycle, invasion, and radiosensitivity were measured under normal or hypoxic condition. Radiosensitivity was tested in two mice PCa models (the LNCaP orthotopic BALB/c-nu mice model and the C4-2B subcutaneous SCID mice model). Results: In both LNCaP and C4-2B cells, HIF-1α transfection led to an enhanced ß-catenin nuclear translocation, while ß-catenin silencing inhibited the ß-catenin nuclear translocation. Enhanced ß-catenin nuclear translocation caused by HIF-1α overexpression resulted in enhanced cell proliferation and invasion, altered cell cycle distribution, reduced apoptosis, and improved non-homologous-end-joining (NHEJ) repair under irradiation condition. In vivo imaging of orthotopic models showed that HIF-1α overexpression LNCaP cells produced tumors with 3-fold volume (P=0.003 1) and 2-fold wet weight (P=0.039 4) than those by negative control cells at day 21, and ß-catenin silencing cells aberrantly reduced both tumor volume (P=0.000 3) and wet weight (P=0.017 5) than HIF-1α overexpression cells. In addition, C4-2B subcutaneous models showed similar tumor promotion effects induced by HIF-1α overexpression (tumor volume: P=0.000 1 and wet weight: P=0.047 3) and suppressive effects by ß-catenin silencing (tumor volume: P<0.000 1 and wet weight: P=0.022 1) as LNCaP orthotopic xenograft with regard to tumor volume and wet weight. Conclusions: HIF-1α overexpression enhanced ß-catenin nuclear translocation, which led to the activation of the ß-catenin/NHEJ signaling pathway and increased cell proliferation, invasion, and DNA repair. These results suggest that HIF-1α overexpression led to radioresistance of PCa cells.

[The relationship between smoking and hyperuricemia in Chinese residents].

Objective: To explore the relationship between smoking and hyperuricemia in Chinese residents. Methods: Based on data from the China Health and Nutrition Survey (CHNS), residents with blood samples provided in the 2009 round (including information of socio-demographic factors, lifestyle behaviors, medical history, and laboratory examinations etc.) were selected as the participants in the current analysis. Unconditional logistic regression models were utilized to compute the ORs and corresponding 95%CIs for assessing the relationship between smoking and hyperuricemia. Results: Among the 8 785 subjects, 1 435 had hyperuricemia with a prevalence rate of 16.3%, consisting of 886 men and 549 women with prevalence rates of 21.6% (886/4 110) and 11.7% (549/4 675) , respectively. Compared with never smokers, the adjusted OR (95%CI) for hyperuricemia was 0.83 (0.70-0.98) among current smokers, 0.77 (0.63-0.94) among current smokers with 20-39 years of smoking, and 0.79 (0.65-0.97) among current smokers with 11-20 cigarettes per day. When stratified by gender and compared with non-smoker, the adjusted OR (95%CI) for hyperuricemia among current smokers compared with never smokers was 0.83 (0.70-0.98) among men, while no significant association was found in female current smokers (OR=0.73, 95%CI: 0.42-1.26, P=0.260). Conclusion: In Chinese residents, there is an inverse association between smoking and hyperuricemia prevalence, and this association may be related to duration and intensity of smoking among current smokers. The findings need to be validated in large prospective cohort studies.

Laparoscopic Repair of Incisional Hernia Following Liver Transplantation-Early Experience of a Single Institution in Taiwan.

BACKGROUND: Ventral incisional hernia (VIH) is not uncommon following liver transplantation. Open repair was traditionally adopted for its management. Laparoscopic repair of VIH has been performed successfully in nontransplant patients with evidence of reduced recurrence rates and hospital stay. However, the application of VIH in post-transplantation patients has not been well established. Herein, we provide our initial experience with laparoscopic repair of post-transplantation VIH. METHODS: From March 2015 to March 2016, 18 cases of post-transplantation VIH were subjected to laparoscopic repair (laparoscopy group). A historical control group of 17 patients who underwent conventional open repair (open group) from January 2013 to January 2015 were identified for comparison. The demographics and clinical outcomes were retrospectively compared. RESULTS: There were no significant differences among basic demographics between the 2 groups. No conversion was recorded in the laparoscopy group. Recurrence of VIH up to the end of the study period was not noted. In the laparoscopy group, the minor complications were lower (16.7% vs 52.9%; P = .035), the length of hospital stay was shorter (3 d vs 7 d, P = .007), but the median operative time was longer (137.5 min vs 106 min; P = .003). CONCLUSIONS: Laparoscopic repair of post-transplantation VIH is a safe and feasible procedure with shorter length of hospital stay.