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Objective: This study aimed to assess the impact of preoperative chronic kidney disease (CKD) on the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who underwent standard radical nephroureterectomy (RNU). Methods: A total of 1172 UTUC patients who received RNU at a single center in Taiwan between February 2005 and August 2019 were included. The patients were categorized into two groups based on their preoperative CKD stage: CKD stage ≤3 (811 patients) and CKD stage >3 (361 patients). The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. The study investigated the oncological outcomes, including intravesical recurrence, non-urothelial recurrence, and cancer-specific mortality, stratified by preoperative CKD status. Results: The main findings indicated that UTUC patients with CKD stage >3 in Taiwan exhibited a higher proportion of females (p 3 and CKD stage ≤3 groups. The study also demonstrated that patients with concurrent bladder cancer and variant histology had higher rates of intravesical recurrence, non-urothelial recurrence, and cancer-specific mortality. The CKD stage >3 group exhibited lower rates of intravesical recurrence (p = 0.0014), higher rates of non-urothelial recurrence (p 3 exhibit distinct characteristics compared to the general population with urothelial carcinoma. They are associated with a non-smoking status, a higher proportion of females, and less aggressive pathological features. Additionally, CKD stage >3 can serve as a clinical indicator for intravesical and non-urothelial recurrence. Further investigation into molecular aspects and treatment modifications for these patients is warranted.

Artemisinin biosynthesis, unique to Artemisia annua, is suggested to have evolved from the ancestral costunolide biosynthetic pathway commonly found in the Asteraceae family. However, the evolutionary landscape of this process is not fully understood. The first oxidase in artemisinin biosynthesis, CYP71AV1, also known as amorpha-4,11-diene oxidase (AMO), has specialized from ancestral germacrene A oxidases (GAOs). Unlike GAO, which exhibits catalytic promiscuity toward amorpha-4,11-diene, the natural substrate of AMO, AMO has lost its ancestral activity on germacrene A. Previous studies have suggested that the loss of the GAO copy in A. annua is responsible for the abolishment of the costunolide pathway. In the genome of A. annua, there are two copies of AMO, each of which has been reported to be responsible for the different product profiles of high- and low-artemisinin production chemotypes. Through analysis of their tissue-specific expression and comparison of their sequences with those of other GAOs, it was discovered that one copy of AMO (AMOHAP) exhibits a different transcript compared to the reported artemisinin biosynthetic genes and shows more sequence similarity to other GAOs in the catalytic regions. Furthermore, in a subsequent in vitro enzymatic assay, the recombinant protein of AMOHAP unequivocally demonstrated GAO activity. This result clearly indicates that AMOHAP is a GAO rather than an AMO and that its promiscuous activity on amorpha-4,11-diene has led to its misidentification as an AMO in previous studies. In addition, the divergent expression pattern of AMOHAP compared to that of the upstream germacrene A synthase may have contributed to the abolishment of costunolide biosynthesis in A. annua. Our findings reveal a complex evolutionary landscape in which the emergence of a new metabolic pathway replaces an ancestral one.

Objective To assess the efficacy of dynamic changes in lymphocyte-C-reactive protein ratio (LCR) on differentiating disease severity and predicting disease progression in adult patients with Coronavirus disease 2019 (COVID-19). Methods This single-centre retrospective study enrolled adult COVID-19 patients categorized into moderate, severe and critical groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data were collected. LCR and sequential organ failure assessment (SOFA) score were calculated. Lymphocyte count and C-reactive protein (CRP) levels were monitored on up to four occasions. Disease severity was determined concurrently with each LCR measurement. Results This study included 145 patients assigned to moderate ( n = 105), severe ( n = 33) and critical groups ( n = 7). On admission, significant differences were observed among different disease severity groups including age, comorbidities, neutrophil proportion, lymphocyte count and proportion, D-Dimer, albumin, total bilirubin, direct bilirubin, indirect bilirubin, CRP and SOFA score. Dynamic changes in LCR showed significant differences across different disease severity groups at different times, which were significantly inversely correlated with disease severity of COVID-19, with correlation coefficients of −0.564, −0.548, −0.550 and −0.429 at four different times. Conclusion Dynamic changes in LCR can effectively differentiate disease severity and predict disease progression in adult COVID-19 patients.

BackgroundInitial choices of antimicrobial therapy for most cases of community-acquired pneumonia (CAP) in children under 5 years of age are typically based on local epidemiology, risk factors assessment, and subsequent clinical parameters and positive cultures, which can lead to the underdiagnosis and underestimation of lung infections caused by uncommon pathogens. Contezolid, an orally administered oxazolidinone antibiotic, gained approval from the National Medical Products Administration (NMPA) of China in June 2021 for managing complicated skin and soft tissue infections (cSSTI) caused by staphylococcus aureus (SA), streptococcus pyogenes, or streptococcus agalactis. Owing to its enhanced safety profile and ongoing clinical progress, the scope of contezolid's clinical application continues to expand, benefiting a growing number of patients with Gram-positive bacterial infections.Case summaryIn this report, we present the first use of contezolid in a toddler with severe CAP caused by SA, aiming to avoid potential adverse drug reactions (ADRs) associated with vancomycin and linezolid.ConclusionAlthough contezolid has not been officially indicated for CAP, it has been shown to be effective and safe in the management of SA-induced severe CAP in this toddler, suggesting its potential as an alternative option in the dilemma, especially for patients who are susceptible or intolerant to ADRs associated with first-line anti-methicillin-resistant staphylococcus aureus (MRSA) antimicrobial agents.

Background: Semantic segmentation is crucial in medical image diagnosis. Traditional deep convolutional neural networks excel in image classification and object detection but fall short in segmentation tasks. Enhancing the accuracy and efficiency of detecting high-level cervical lesions and invasive cancer poses a primary challenge in segmentation model development. Methods: Between 2018 and 2022, we retrospectively studied a total of 777 patients, comprising 339 patients with high-level cervical lesions and 313 patients with microinvasive or invasive cervical cancer. Overall, 1554 colposcopic images were put into the DeepLabv3+ model for learning. Accuracy, Precision, Specificity, and mIoU were employed to evaluate the performance of the model in the prediction of cervical high-level lesions and cancer. Results: Experiments showed that our segmentation model had better diagnosis efficiency than colposcopic experts and other artificial intelligence models, and reached Accuracy of 93.29 %, Precision of 87.2 %, Specificity of 90.1 %, and mIoU of 80.27 %, respectively. Conclution: The DeepLabv3+ model had good performance in the segmentation of cervical lesions in colposcopic post-acetic-acid images and can better assist colposcopists in improving the diagnosis.

This study is aimed at investigating the effects of exogenous selenium (Se) on the ionic equilibrium and micro-domain distribution, state transitions between photosystem I (PSI) and photosystem II (PSII), and the photosynthetic carbon assimilation efficiency of tomato (Solanum lycopersicon L.) seedlings under the influence of salt stress. The application of 0.01 mmol•L-1 exogenous Se had no significant effects on the selective transport capacity of sodium (Na), potassium (K), calcium (Ca) and magnesium (Mg) from the roots to leaves under salt stress. It, however, significantly hindered the absorption of Na by the root system and leaves, increased the ratios of K/Na, Ca/Na and Mg/Na, and relieved the nonuniformity of micro-domain ionic distribution, thus, mitigating the ionic homeostasis imbalance and ion toxicity induced by salt stress. Additionally, the application of exogenous Se overcame stomatal limitation, regulated the state transitions between PSI and PSII, and enhanced the initial and overall activity of Rubisco as well as the activities of Rubisco activase (RCA) and fructose-1,6-bisphosphatase (FBPase). It also increased the levels of expression of nine relevant genes in Calvin cycle, which subsequently improved the concentration of photosynthetic substrates, balanced the distribution of activation energy between PSI and PSII, promoted the efficiency of CO2 carboxylation and carbon assimilation, thereby increasing the photosynthetic efficiency of tomato seedling leaves under salt stress. Hence, the supply of exogenous Se can alleviate the inhibition of salt stress on tomato seedling growth by rebuilding ionic homeostasis and promoting photosynthetic capacity.

In this paper, a coupling model of SWAT (Soil and Water Assessment Tool) and EFDC (Environmental Fluid Dynamics Code) was established, and the relationship between the pollution source and water quality response was identified. Based on the hydrodynamic water quality simulation results and the one-dimensional WEC (water environmental capacity) theoretical formula, the total nitrogen and total phosphorus WEC and the remaining WEC of the Yongzhou Section of Xiangjiang River Basin under the guaranteed rate of 90% and in 2017 were calculated, respectively. It can be seen from the results that the total nitrogen WEC of the Yongzhou Section of Xiangjiang River Basin in 2017 is 27,673.04 t, the total nitrogen WEC under the guaranteed rate of 90% is 19,497.61 t/a and the total phosphorus WEC of the Yongzhou Section of Xiangjiang River Basin in 2017 is 4,877.22 t. The total phosphorus WEC under the guaranteed rate of 90% is 2,936.64 t/a; in 2017, the remaining WECs of total nitrogen and total phosphorus in the entire basin are 14,646.69 and 3,358.67 t, respectively. HIGHLIGHTS A calculation method of water environment capacity was studied, which can provide a reference for the calculation of water environment capacity in large and medium-sized basins; The coupling model of SWAT and EFDC fix the lack of watershed sites and measured data, and inaccurate calculation of water environment capacity.; The coupling model identifies the relationship between pollution sources and water quality response.;

PurposeTo evaluate the prognostic impact of the lowest level of tumor location for upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU).Materials and methodsData were collected from patients with UTUC treated with RNU (01/2005- 06/2020) at a single center in Taiwan. Patients were stratified by the lowest level of tumor location into three groups: renal pelvis only (RPO), above upper ureter (AUU), and below upper ureter (BUU). We compared characteristics between groups and examined the association of the lowest level of tumor involvement with intravesical recurrence (IVR), systemic metastasis (SM), and cancer-specific mortality (CSM).ResultsOverall, 1239 patients (542 RPO, 260 AUU, 437 BUU) were enrolled. Concurrent bladder cancer, multifocality, tumor architecture, lymphovascular invasion, carcinoma in situ, and variant histology were significantly different across different tumor locations. BUU had worse five-year intravesical recurrence (IVR), systemic metastasis (SM) and cancer-specific mortality (CSM) (p < 0.001, p = 0.056 and p = 0.13, respectively). In multivariable models, the lowest level of tumor involvement was an independent predictor of IVR (AUU hazard ratio (HR) = 1.52, p = 0.007; BUU HR = 1.75, p < 0.001), but only BUU was an independent predictor of SM (HR = 1.61, p = < 0.001) and CSM (HR = 1.51, p = 0.008).ConclusionThe lowest level of tumor involvement in UTUC, especially BUU, was associated with a higher risk of IVR, SM and CSM. Assessment of the lowest level of tumor involvement after RNU may help identify patients who require more intensive follow-up.

Cancer immunotherapy uses the immune system to achieve therapeutic effects; however, its effect is still limited. Therefore, in addition to immune checkpoint-based treatment, the development of other strategies that can inhibit cancer cells from resisting immune cytotoxicity is important. There are currently few studies on the mechanism of tumors using cytoskeletal proteins reorganization to participate in immune escape. In this study, we identified cancer cell lines that were sensitive or resistant to natural killer cells in urothelial and lung cancer using the natural killer cell sensitivity assay. We found that immunoresistant cancer cells avoid natural killer cell-mediated cytotoxicity by upregulation of vimentin and remodeling of actin cytoskeleton. Immunofluorescence staining showed that immune cells promoted the formation of actin filaments at the immune synapse, which was not found in immunosensitive cancer cells. Pretreatment of the actin polymerization inhibitors latrunculin B increased the cytotoxicity of natural killer cells, suggesting that cytoskeleton remodeling plays a role in resisting immune cell attack. In addition, silencing of vimentin with shRNA potentiated the cytotoxicity of natural killer cells. Interestingly, the upregulation and extension of vimentin was found in tumor islands of upper tract urothelial carcinoma infiltrated by natural killer cells. Conversely, tumors without natural killer cell invasion showed less vimentin signal. The expression level of vimentin was highly correlated with natural killer cell infiltration. In summary, we found that when immune cells attack cancer cells, the cancer cells resist immune cytotoxicity through upregulated vimentin and actin reorganization. In addition, this immune resistance mechanism was also found in patient tumors, indicating the possibility that they can be applied to evaluate the immune response in clinical diagnosis.

Versican (VCAN), also known as extracellular matrix proteoglycan 2, has been suggested as a potential biomarker in cancers. Previous research has found that VCAN is highly expressed in bladder cancer. However, its role in predicting outcomes for patients with upper urinary tract urothelial cancer (UTUC) is not well understood. In this study, we collected tissues from 10 patients with UTUC, including 6 with and 4 without lymphovascular invasion (LVI), a pathological feature that plays a significant role in determining metastasis. Results from RNA sequencing revealed that the most differentially expressed genes were involved in extracellular matrix organization. Using the TCGA database for clinical correlation, VCAN was identified as a target for study. A chromosome methylation assay showed that VCAN was hypomethylated in tumors with LVI. In our patient samples, VCAN expression was also found to be high in UTUC tumors with LVI. In vitro analysis showed that knocking down VCAN inhibited cell migration but not proliferation. A heatmap analysis also confirmed a significant correlation between VCAN and migration genes. Additionally, silencing VCAN increased the effectiveness of cisplatin, gemcitabine and epirubicin, thus providing potential opportunities for clinical application.

Safe and effective vaccines and therapeutics based on the understanding of antiviral immunity are urgently needed to end the COVID-19 pandemic. However, the understanding of these immune responses, especially cellular immune responses to SARS-CoV-2 infection, is limited. Here, we conducted a cohort study of COVID-19 patients who were followed and had blood collected to characterize the longitudinal dynamics of their cellular immune responses. Compared with healthy controls, the percentage of activation of SARS-CoV-2 S/N-specific T cells in recovered patients was significantly higher. And the activation percentage of S/N-specific CD8+ T cells in recovered patients was significantly higher than that of CD4+ T cells. Notably, SARS-CoV-2 specific T-cell responses were strongly biased toward the expression of Th1 cytokines, included the cytokines IFNγ, TNFα and IL2. Moreover, the secreted IFNγ and IL2 level in severe patients was higher than that in mild patients. Additionally, the number of IFNγ-secreting S-specific T cells in recovered patients were higher than that of N-specific T cells. Overall, the SARS-CoV-2 S/N-specific T-cell responses in recovered patients were strong, and virus-specific immunity was present until 14-16 weeks after symptom onset. Our work provides a basis for understanding the immune responses and pathogenesis of COVID-19. It also has implications for vaccine development and optimization and speeding up the licensing of the next generation of COVID-19 vaccines.

Background: Oncologic outcomes for pT2N0M0 upper tract urothelial carcinoma (UTUC) after nephroureterectomy are not well defined, with most previous studies focused on a heterogeneous population. Therefore, we aimed to investigate the clinical determinants of extraurinary tract recurrence and survival after radical surgery in patients with localized UTUC. Methods: We retrospectively identified 476 patients with pT2N0M0 UTUC who underwent radical nephroureterectomy or ureterectomy between October 2002 and March 2022. To evaluate the prognostic impact, patients were divided into renal pelvic, ureteral, and both-region (renal pelvis plus synchronous ureter) groups based on tumor location. The outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Associations were evaluated using multivariable Cox regression analyses for prognostic factors and Kaplan–Meier analyses for survival curves. Results: The renal pelvic, ureteral, and both-region groups consisted of 151 (31.7%), 314 (66.0%), and 11 (2.3%) patients, respectively. Kaplan–Meier analyses comparing the three tumor types showed significant differences in 5-year RFS (83.6% vs. 73.6% vs. 52.5%, p = 0.013), CSS (88.6% vs. 80.7% vs. 51.0%, p = 0.011), and OS (83.4% vs. 70.1% vs. 45.6%, p = 0.002). Multivariable analyses showed that age >60 years, previous bladder cancer history, ureteral involvement (ureteral and both-regional groups), and positive surgical margins were significant negative prognostic factors for the studied outcomes. Conclusions: Patients with pT2 UTUC and presence of ureteral involvement had more frequent disease relapse. Subsequent adjuvant therapy regimens and close follow-up in patients with negative prognostic factors are warranted despite complete pathological removal of the tumor.

Active and passive anti-Aβ immunotherapies have successfully been used for the prevention and treatment of Alzheimer’s disease animal models. However, clinical use of these immunotherapies is not effective, because the vaccination is administered too late. At 1 month of age, 100 μL of Aβ3–10-KLH peptide (vaccine, 2 μg/μL) was subcutaneously injected into the neck of an amyloid precursor protein/presenilin-1/tau transgenic (3×Tg-AD) mouse model. Aβ3–10-KLH peptide was re-injected at 1.5, 2.5, 3.5, 4.5, 5.5, and 6.5 months of age. Serum levels of Aβ antibody were detected by enzyme-linked immunosorbent assay, while spatial learning and memory ability were evaluated by Morris water maze. Immunohistochemistry was used to detect total tau with HT7 and phosphorylated tau with AT8 (phosphorylation sites Ser202 and Thr205) and AT180 (phosphorylation site Thr231) antibodies in the hippocampus. In addition, western blot analysis was used to quantify AT8 and AT180 expression in the hippocampus. The results showed that after vaccine injection, mice produced high levels of Aβ antibody, cognitive function was significantly improved, and total tau and phosphorylated tau levels were significantly reduced. These findings suggest that early active immunization with Aβ3–10-KLH vaccine can greatly reduce tau phosphorylation, thereby mitigating the cognitive decline of 3×Tg-AD mice. This study was approved by the Animal Ethics Committee of China Medical University, China (approval No. 103-316) on April 2, 2016.

Mitochondria are important organelles responsible for energy production, redox homeostasis, oncogenic signaling, cell death, and apoptosis. Deregulated mitochondrial metabolism and biogenesis are often observed during cancer development and progression. Reports have described the crucial roles of mitochondria in urothelial carcinoma (UC), which is a major global health challenge. This review focuses on research advances in the role of mitochondria in UC. Here, we discuss the pathogenic roles of mitochondria in UC and update the mitochondria-targeted therapies. We aim to offer a better understanding of the mitochondria-modulated pathogenesis of UC and hope that this review will allow the development of novel mitochondria-targeted therapies.

Background: Circulating tumor cells (CTCs) with an epithelial-mesenchymal transition phenotype in peripheral blood may be a useful marker of carcinomas with poor prognosis. The aim of this study was to determine the prognostic significance of CTCs expressing Krüppel-like factor 8 (KLF8) and vimentin in pancreatic cancer (PC). Methods: CTCs were isolated by immunomagnetic separation from the peripheral blood of 40 PC patients before undergoing surgical resection. Immunocytochemistry was performed to identify KLF8 + and vimentin + CTCs. The associations between CTCs and time to recurrence (TTR), clinicopathologic factors, and survival were assessed. Univariate and multivariate analyzes were performed to identify risk factors. Results: Patients with CTCs ( n = 30) had a higher relapse rate compared to those without ( n = 10) (70.0% vs 20.0%; P < 0.01). The proportion of KLF8 + /vimentin + CTCs to total CTCs was inversely related to TTR ( r = −0.646; P < 0.01); TTR was reduced in patients with > 50% of CTCs identified as KLF8 + /vimentin + ( P < 0.01). Independent risk factors for recurrence were perineural invasion and > 50% KLF8 + /vimentin + CTCs (both P < 0.05). Conclusion: Poor prognosis can be predicted in PC patients when > 50% of CTCs are positive for KLF8 and vimentin.

In this study, the protective role of exogenous ascorbic acid (AsA) on salt-induced inhibition of photosynthesis in the seedlings of processing tomatoes under salt stress has been investigated. Plants under salt stress (NaCl, 100 mmol/L) were foliar-sprayed with AsA (0.5 mmol/L), lycorine (LYC, 0.25 mmol/L, an inhibitor of key AsA synthesis enzyme l-galactono-γ-lactone dehydrogenase activity), or AsA plus LYC. The effects of AsA on fast OJIP fluorescence rise curve and JIP parameters were then examined. Our results demonstrated that applying exogenous AsA significantly changed the composition of O-J-I-P fluorescence transients in plants subjected to salt stress both with and without LYC. An increase in basal fluorescence (Fo) and a decrease in maximum fluorescence (Fm) were observed. Lower K- and L-bands and higher I-band were detected on the OJIP transient curves compared, respectively, with salt-stressed plants with and without LYC. AsA application also significantly increased the values of normalized total complementary area (Sm), relative variable fluorescence intensity at the I-step (VI), absorbed light energy (ABS/CSm), excitation energy (TRo/CSm), and reduction energy entering the electron transfer chain beyond QA (ETo/CSm) per reaction centre (RC) and electron transport flux per active RC (ETo/RC), while decreasing some others like the approximated initial slope of the fluorescence transient (Mo), relative variable fluorescence intensity at the K-step (VK), average absorption (ABS/RC), trapping (TRo/RC), heat dissipation (DIo/RC) per active RC, and heat dissipation per active RC (DIo/CSm) in the presence or absence of LYC. These results suggested that exogenous AsA counteracted salt-induced photoinhibition mainly by modulating the endogenous AsA level and redox state in the chloroplast to promote chlorophyll synthesis and alleviate the damage of oxidative stress to photosynthetic apparatus. AsA can also raise the efficiency of light utilization as well as excitation energy dissipation within the photosystem II (PSII) antennae, thus increasing the stability of PSII and promoting the movement of electrons among PS1 and PSII in tomato seedling leaves subjected to salt stress.

The effects of exogenous GSH (reduced glutathione) on photosynthetic characteristics, photosystem II efficiency, absorbed light energy allocation and the H2O2-scavenging system in chloroplasts of salt-stressed tomato (Solanum lycopersicum L.) seedlings were studied using hydroponic experiments in a greenhouse. Application of exogenous GSH ameliorated saline-induced growth inhibition, the disturbed balance of Na+ and Cl− ions and Na+/K+ ratios, and the reduction of the net photosynthetic rate (Pn). GSH also increased the maximal photochemical efficiency of PSII (Fv/Fm), the electron transport rate (ETR), the photochemical quenching coefficient (qP), and the non-photochemical quenching coefficient (NPQ). In addition, GSH application increased the photochemical quantum yield (Y(II)) and relative deviation from full balance between the photosystems (β/α–1) and decreased the PSII excitation pressure (1–qP) and quantum yield of non-regulated energy dissipation (Y(NO)) in leaves of salt-stressed tomatoes without BSO (L-buthionine-sulfoximine, an inhibitor of key GSH synthesis enzyme γ-glutamylcysteine synthetase) or with BSO. Further, the addition of GSH depressed the accumulation of H2O2 and malondialdehyde (MDA), induced the redistribution of absorbed light energy in PSII reaction centers, and improved the endogenous GSH content, GSH/GSSH ratio and activities of H2O2-scavenging enzymes (including superoxidase dismutase (SOD), catalase (CAT), peroxidase (POD) and key enzymes in the AsA-GSH cycle and Grx system) in the chloroplasts of salt-stressed plants with or without BSO. Therefore, GSH application alleviates inhibition of salt-induced growth and photosynthesis mainly by overcoming stomatal limitations, improving the PSII efficiency, and balancing the uneven distribution of light energy to reduce the risk of ROS generation and to mediate chloroplast redox homeostasis and the antioxidant defense system to protect the chloroplasts from oxidative damage. Thus, GSH may be used as a potential tool for alleviating salt stress in tomato plants.

PurposeTo assess the association of tumor architecture with cancer recurrence, metastasis, and cancer-specific survival (CSS) in patients treated with radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC) in Taiwan.Materials and MethodsData were collected from 857 patients treated with RNU between January 2005 and August 2016 in our hospital. Pathologic slides were reviewed by genitourinary pathologists. Propensity score weighting was performed for data analysis.ResultsSessile growth pattern was observed in 212 patients (24.7%). Tumor architecture exhibited a significant association with bladder cancer history, chronic kidney disease (CKD), tumor stage, lymph node status, histological grade, lymphovascular invasion, concomitant carcinoma in situ, and the variant type [standardized mean difference (SMD) > 0.1 for all variables before weighting]. In the propensity score analysis, 424 papillary and sessile tumor architecture were analyzed to balance the baseline characteristics between the groups. Tumor architecture was an independent predictor of metastatic disease and CSS (p = 0.033 and p = 0.002, respectively). However, the associations of tumor architecture with bladder and contralateral recurrence were nonsignificant (p = 0.956 and p = 0.844, respectively).ConclusionsTumor architecture of UTUC after RNU is associated with established features of aggressive disease and predictors of metastasis and CSS. Assessment of tumor architecture may help identify patients who could benefit from close follow-up or early administration of systemic therapy after RNU. Tumor architecture should be included in UTUC staging after further confirmation.

Urothelial carcinoma includes upper urinary tract cancer (UTUC) and bladder cancer. Although nephroureterectomy is the standard treatment for UTUC, the recurrence rate is approximately half and the tumor is associated with poor prognoses. Metastases are the most devastating and lethal clinical situation in urothelial carcinoma. Despite its clinical importance, few potential diagnostic biomarkers are suitable for early UC detection. We compared high-stage/high-grade urothelial carcinoma tissues to adjacent normal urothelial tissues using methyl-CpG binding domain protein capture for genome-wide DNA methylation analysis. Based on our findings, inhibin βA (INHBA) might be associated with carcinogenesis and metastasis. Further, clinical UC specimens had significant INHBA hypomethylation based on pyrosequencing. INHBA was detected by real-time PCR and immunohistochemistry staining, and was found to be highly expressed in clinical tissues and cell lines of urothelial carcinoma. Further, INHBA depletion was found to significantly reduce BFTC-909 cell growth and migration by INHBA-specific small interfering RNA. Interestingly, a positive correlation was found between SMAD binding and extracellular structure organization with INHBA using gene set enrichment analysis and gene ontology analysis. Together, these results are the first evidence of INHBA promoter hypomethylation and INHBA overexpression in UTUC. INHBA may affect urothelial carcinoma migration by reorganizing the extracellular matrix through the SMAD pathway.

The emergence and dissemination of carbapenem-resistant Escherichia coli (E. coli) strains is a main risk for global public health, but little is known of carbapenemase producing E. coli in Henan, China. The study was undertaken to investigate the prevalence and mechanism of carbapenem-resistant E. coli strains in a hospital in Xinxiang, Henan, China, 2014. A total of 5 carbapenemase-producing E. coli strains were screened from 1014 isolates. We found that they were all resistant to meropenem and imipenem. Amikacin showed the best sensitivity, with gentamicin coming up next. The positive rate of blaNDM was 80% (4/5). The sequencing results showed that two isolates belonged to blaNDM-1 whereas other 2 isolates carried the blaNDM-5. Other carbapenemase genes including blaIMP, blaVIM, blaKPC and blaOXA-48 were not detected. The blaCTX-M-15, blaTEM-1, sul2, aad, and aac(6”)–Ib–cr were also detected. MLST analysis showed that NDM-producing E. coli were sporadic. Conjugation test indicated blaNDM could be transferred. In conclusion, the blaNDM was the principal resistance mechanism of carbapenem-resistant E. coli in the hospital, Henan, China. Keywords: blaNDM, Carbapenem-resistant, Escherichia coli

AIM: To investigate the changes of serum levels of vascular endothelial growth factor(VEGF), Endostatin(ES), thrombospondin(TSP), tissue kallikrein(TKLK)and soluble intercellular adhesion molecule-1(sICAM-1)in patients with diabetic retinopathy(DR)and its clinical significance. METHODS: Selected 60 patients with non-proliferative diabetic retinopathy(NPDR group), 60 patients with proliferative diabetic retinopathy(PDR group)were enrolled in this study. Sixty diabetic patients without diabetic retinopathy(DM group)and 60 healthy people(control group)were also enrolled. Collection time was from January 2014 to December 2016. Serum levels of VEGF, ES, TSP, TKLK and sICAM-1 were measured and compared. RESULTS: The levels of serum VEGF, TKLK and sICAM-1 in PDR group were significantly higher than those in NPDR group, DM group and control group(PPPPPP>0.05). CONCLUSION: The levels of serum ES, TSP, TKLK and sICAM-1 in patients with DR have changed significantly, and the process of retinopathy has been affected by regulating the level of VEGF.

Upper urinary tract urothelial carcinoma (UTUC) is a relatively rare cancer with a poor prognosis if diagnosed at an advanced stage. Although cisplatin-based chemotherapy is a common treatment strategy, it has a limited response rate. Shock wave lithotripsy is a common treatment for upper urinary tract stones. Low-energy shock waves (LESWs) temporarily increase tissue permeability and enhance drug penetration to the targeted tissue. However, no study has investigated the efficacy of the combination of shock wave lithotripsy and chemotherapy in UTUC. Hence, in this study, we aimed to identify the potential application of the combination of LESW and chemotherapy in UTUC. We evaluated the synergistic effects of LESW and cisplatin in vitro, in vivo, and in patient-derived organoid (PDO) models. Compared with cisplatin alone, the combination treatment caused more significant tumour suppression in vitro and in animal models, without increased toxicity. Histological examination showed that compared with animals treated with cisplatin alone, those who received the combination treatment showed more deteriorated cell arrangement and cell oedema. Moreover, LESW improved the cytotoxicity of cisplatin in the preclinical PDO model of UTUC. Thus, LESW combined with cisplatin is a potential new antitumour strategy for improving the treatment response in locally advanced UTUC.

Ribosome-binding protein 1 (RRBP1) is a potential oncogene in several cancer types. However, the correlation between RRBP1 expression and the prognosis of patients with upper tract urothelial carcinoma (UTUC) remains unclear. In this study, we identified that RRBP1 is associated with carcinogenesis and metastasis in UTUC using a methylation profiling microarray. High correlations between RRBP1 and cancer stages, nodal metastasis status, molecular subtypes, and prognosis in bladder urothelial cancer (BLCA) were found. Aberrant DNA methylation in the gene body region of RRBP1 was determined in UTUC tissues by methylation-specific PCR. RRBP1 expression was significantly increased in UTUC tissues and cell lines, as determined by real-time PCR and immunohistochemistry. RRBP1 depletion significantly reduced BFTC909 cell growth induced by specific shRNA. On the other hand, molecular subtype analysis showed that the expression of RRBP1 was associated with genes related to cell proliferation, epithelial–mesenchymal transition, and basal markers. A patient-derived organoid model was established to analyze patients’ responses to different drugs. The expression of RRBP1 was related to chemoresistance. Taken together, these results provide the first evidence that RRBP1 gene body hypomethylation predicts RRBP1 high expression in UTUC. The data highlight the importance of RRBP1 in UTUC malignancy and chemotherapeutic tolerance.

Preserving renal function and controlling oncological outcomes are pertinent when managing renal neoplasms. Cryoablation is the recommended treatment only for clinical T1a stage renal tumour. Here, we compared the outcomes of robot-assisted laparoscopic partial nephrectomy (RaPN) and laparoscopic cryoablation (LCA) in the treatment of patients with localised T1-T2 renal tumours. Overall, 86 patients who received RaPN and 78 patients underwent LCA were included in this study. The intraoperative, postoperative, and oncological outcomes in the LCA group were non-inferior to the RaPN group. Moreover, LCA demonstrated shorter operative time (267.45 ± 104.53 min vs. 138.56 ± 45.28 min, p < 0.001), lower blood loss (300.56 ± 360.73 mL vs. 30.73 ± 50.31 mL, p < 0.001), and slight renal function deterioration because of the reduced invasiveness, without compromising on the oncological outcomes.

Background Anti-thymocyte globulin (ATG) as induction therapy in renal transplantation is facing the dilemma of reducing the incidence of acute rejection (AR) and delayed graft function (DGF) or increasing risks of infection and malignancy. The purpose of this study was to delineate the safety and efficiency of the optimal ATG dosage. Methods We retrospectively evaluated 91 deceased donor kidney transplant recipients (KTRs) in our institution between March 2011 and January 2019. The patients were classified into three groups based on induction therapy: (1) Group 1: modest-dose ATG (three mg/kg) intraoperatively (N = 21); (2) Group 2: low-dose ATG (1–1.5 mg/kg) intraoperatively (N = 23); (3) Group 3: basiliximab 20 mg both on day 0 and 4 (N = 47). In Groups 1 and 2, all patients received a daily low-dose program (1–1.5 mg/kg each day) with target dosage of six mg/kg. Induction therapy was combined with standard immunosuppressive regimen consisting of calcineurin inhibitors, mycophenolate/the mammalian target of rapamycin inhibitors and corticosteroids. Results There was no significant difference in patient characteristics among groups. The outcomes of infection rate, biopsy-proven acute rejection, post-transplant diabetes mellitus, graft survival, and patient survival were similar among groups. Compared to the daily low-dose ATG regimen, the intraoperative modest-dose regimen did not cause more dose interruption and hence was more likely to reach the target ATG dosage. The intraoperative modest-dose regimen also seemed to reduce the rate of DGF. Discussion In recent years, a trend of using a “lower” dose of ATG has seemed to emerge. Our results suggest intraoperative modest-dose ATG followed by daily low-dose ATG regimen was safe and effective in cadaveric renal transplantations for preventing DGF, AR, and graft loss.

Spring maize is one of the most popular crops planted in northeastern China. The cropping systems involving spring maize have been maintaining high production through intensive management practices. However, the high rates of nitrogen (N) fertilizers application could have introduced a great amount of nitrous oxide (N2O) into the atmosphere. It is crucial for sustaining the maize production systems to reduce N2O emissions meanwhile maintaining the optimum yields by adopting alternative farming management practices. The goal of this study was to evaluate effects of alternative fertilization and crop residue management practices on N2O emission as well as crop yield for a typical maize field in northeastern China. Field experiments were conducted during the 2010-2011 maize growing seasons (from early May to late September) in Liaoning Province, northeastern China. N2O fluxes were measured at the field plots with six different treatments including no N fertilizer use (CK), farmers’ conventional N fertilizer application rate (FP), reduced N fertilizer rate (OPT), reduced N fertilizer rate combined with crop straw amendment (OPTS), slow-release N fertilizer (CRF), and reduced N fertilizer rate combined with nitrification inhibitor (OPT+DCD). The static chamber method combined with gas chromatography technique was employed to conduct the measurements of N2O fluxes. The field data showed that N2O emissions varied across the treatments. During the maize growing season in 2010, the total N2O emissions under the treatments of CK, FP, OPT, OPTS, and CRF were 0.63, 1.11, 1.03, 1.26, and 0.98 kg N ha−1, respectively. The seasonal cumulative N2O emissions were 0.54, 1.07, 0.96, 1.12, and 0.84 kg N ha−1, respectively, under CK, FP, OPT, OPTS, and OPT+DCD in 2011. In comparison with FP, CRF or OPT+DCD reduced the N2O emissions by 12 or 21%, respectively, while the crop yields remained unchanged. The results indicate that the reduction of N-fertilizer application rate in combination with the slow-release fertilizer type or nitrification inhibitor could effectively mitigate N2O emissions from the tested field. The incorporation of crop residue didn't show positive effect on mitigating N2O emissions from the tested cropping system. The field study can provide useful information for the on-going debate on alternative N fertilization strategies and crop straw management in China. However, further studies would be needed to explore the long-term impacts of the alternative management practices on a wide range of environmental services.

This study is aimed at investigating the effects of exogenous selenium (Se) on the ionic equilibrium and micro-domain distribution, state transitions between photosystem I (PSI) and photosystem II (PSII), and the photosynthetic carbon assimilation efficiency of tomato (Solanum lycopersicon L.) seedlings under the influence of salt stress. The application of 0.01 mmol•L-1 exogenous Se had no significant effects on the selective transport capacity of sodium (Na), potassium (K), calcium (Ca) and magnesium (Mg) from the roots to leaves under salt stress. It, however, significantly hindered the absorption of Na by the root system and leaves, increased the ratios of K/Na, Ca/Na and Mg/Na, and relieved the nonuniformity of micro-domain ionic distribution, thus, mitigating the ionic homeostasis imbalance and ion toxicity induced by salt stress. Additionally, the application of exogenous Se overcame stomatal limitation, regulated the state transitions between PSI and PSII, and enhanced the initial and overall activity of Rubisco as well as the activities of Rubisco activase (RCA) and fructose-1,6-bisphosphatase (FBPase). It also increased the levels of expression of nine relevant genes in Calvin cycle, which subsequently improved the concentration of photosynthetic substrates, balanced the distribution of activation energy between PSI and PSII, promoted the efficiency of CO2 carboxylation and carbon assimilation, thereby increasing the photosynthetic efficiency of tomato seedling leaves under salt stress. Hence, the supply of exogenous Se can alleviate the inhibition of salt stress on tomato seedling growth by rebuilding ionic homeostasis and promoting photosynthetic capacity. [ABSTRACT FROM AUTHOR]