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Background: Vesical Imaging‐Reporting and Data System (VI‐RADS) is a pathway for the standardized imaging and reporting of bladder cancer staging using multiparametric (mp) MRI. Purpose: To investigate additional role of morphological (MOR) measurements to VI‐RADS for the detection of muscle‐invasive bladder cancer (MIBC) with mpMRI. Study Type: Retrospective. Population: A total of 198 patients (72 MIBC and 126 NMIBC) underwent bladder mpMRI was included. Field Strength/Sequence: 3.0 T/T2‐weighted imaging with fast‐spin‐echo sequence, spin‐echo‐planar diffusion‐weighted imaging and dynamic contrast‐enhanced imaging with fast 3D gradient‐echo sequence. Assessment: VI‐RADS score and MOR measurement including tumor location, number, stalk, cauliflower‐like surface, type of tumor growth, tumor‐muscle contact margin (TCM), tumor‐longitudinal length (TLL), and tumor cellularity index (TCI) were analyzed by three uroradiologists (3‐year, 8‐year, and 15‐year experience of bladder MRI, respectively) who were blinded to histopathology. Statistical Tests: Significant MOR measurements associated with MIBC were tested by univariable and multivariable logistic regression (LR) analysis with odds ratio (OR). Area under receiver operating characteristic curve (AUC) with DeLong's test and decision curve analysis (DCA) were used to compared the performance of unadjusted vs. adjusted VI‐RADS. A P‐value <0.05 was considered statistically significant. Results: TCM (OR 9.98; 95% confidence interval [CI] 4.77–20.8), TCI (OR 5.72; 95% CI 2.37–13.8), and TLL (OR 3.35; 95% CI 1.40–8.03) were independently associated with MIBC at multivariable LR analysis. VI‐RADS adjusted by three MORs achieved significantly higher AUC (reader 1 0.908 vs. 0.798; reader 2 0.906 vs. 0.855; reader 3 0.907 vs. 0.831) and better clinical benefits than unadjusted VI‐RADS at DCA. Specially in VI‐RADS‐defined equivocal lesions, MOR‐based adjustment resulted in 55.5% (25/45), 70.4% (38/54), and 46.4% (26/56) improvement in accuracy for discriminating MIBC in three readers, respectively. Data Conclusion: MOR measurements improved the performance of VI‐RADS in detecting MIBC with mpMRI, especially for equivocal lesions. Level of Evidence: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Bird species richness and diversity are the key factors that determine the health and productivity of an ecosystem. They have occupied a marvelous place, i.e., they play a vital role in the contribution of public consideration towards natural habitats and considered as barometers of an ecosystem. This study was carried out to determine the bird species diversity of the Sheikh Badin National Park, located in District Dera Ismail Khan, Khyber Pakhtunkhwa, Pakistan. For this purpose, bird watching surveys following line transect method were conducted from June 2018 to July 2019 in the study area. A total 3408 individuals (1260 migrants and 2148 residents) representing the 41 bird species were recorded during the surveys. Among the total, 18 species were migrants and 23 residents, belong to 11 Orders and 25 Families. Passeriformes was the dominant encompass of 19 species (9 native and 10 migrants) and 13 families. This national park harbored species richness was r = 41, Shannon-Weiner diversity index (H' = 3.546), evenness (J' 0.955) and Simpson's Diversity (D = 0.966). The foraging guild results revealed that the granivore (2274) and insectivore (565) were the most abundant bird species. The major threats to the avifauna were illegal hunting, grazing and deforestation. [ABSTRACT FROM AUTHOR]

Exploring the trade-off and synergy between ecosystem services and their intrinsic impact mechanisms is crucial for improving the overall efficiency of ecosystems and ensuring the sustainable supply of ecosystem services. This study takes the 499 counties in the Yellow River Basin as the research object, uses the Pearson correlation coefficient method to measure the trade-off and synergy among counties, and constructs a geographically weighted logistic regression（GWLR） model to examine the spatiotemporal heterogeneity between balancing synergy and various influencing factors. The results showed that： ① From 2001 to 2021, the ecosystem service value of the Yellow River Basin first increased, then decreased, and finally increased, showing a spatial distribution pattern of "lower in the downstream, higher in the upper and middle reaches." ② Through balancing and collaborative analysis of ecosystem services, it was observed that a balancing relationship between various ecosystem services in the Yellow River Basin during the research period existed between food production and regulation services and support services, and a synergistic relationship existed within and between regulation services and support services. ③ Through initial and secondary screening of potential factors, it was found that six independent variables, including changes in the proportion of construction land, annual average NDVI, annual average precipitation, annual average temperature, population density, and GDP, had a significant impact on the relationship between six groups of ecosystem services. ④ Compared with other factors, changes in the proportion of construction land and the annual average temperature had a stronger spatiotemporal non-stationary response to the balance and synergy of ecosystem services. The research results are beneficial for optimizing ecosystem service efficiency in the Yellow River Basin and providing support for the formulation of refined management measures and policies.

The external spatiotemporal evolution and intrinsic impact mechanisms of ecosystem service value are of great significance for understanding regional ecosystem issues and enhancing human ecological well-being. Based on grid data, this study used the equivalent factor method and NDVI to measure the ecosystem service value of the Yellow River Basin, analyzed the spatial-temporal evolution of urban ecosystem service value along the basin, and established a GWR model to explore the spatial heterogeneity of each influencing factor on the basis of determining the main influencing factors via geographic detector. The results showed that:① The ecosystem service value of the Yellow River Basin increased first, then decreased, and finally increased from 2000 to 2020, showing a spatial distribution pattern of "the south was higher than the north;" "the lower reaches were lower, and the upper and middle reaches were higher;" and the regulation service contributed the most to the ecosystem service value of the basin. ② The results of geographical exploration showed that the degree of influence of various factors was different. Social factors played the strongest role in explaining the ecosystem service value of the Yellow River Basin, followed by economic factors, and natural factors played the weakest role. The high value areas in the upper reaches were mainly related to rivers and lakes, and the high value areas in the middle reaches were mainly related to mountains. ③ The results of the GWR model showed that population density and land reclamation rate were negatively correlated with ecosystem service value, whereas average annual precipitation was positively correlated, and the effects increased from east to west. The GDP per unit area was negatively correlated with the overall ecosystem service value but positively correlated in the upstream region.

OBJECTIVE. The objective of our study was to compare the performance of radiologicradiomic machine learning (ML) models and expert-level radiologists for differentiation of benign and malignant solid renal masses using contrast-enhanced CT examinations. MATERIALS AND METHODS. This retrospective study included a cohort of 254 renal cell carcinomas (RCCs) (190 clear cell RCCs [ccRCCs], 38 chromophobe RCCs [chrRCCs], and 26 papillary RCCs [pRCCs]), 26 fat-poor angioleiomyolipomas, and 10 oncocytomas with preoperative CT examinations. Lesions identified by four expert-level radiologists (> 3000 genitourinary CT and MRI studies) were manually segmented for radiologicradiomic analysis. Disease-specific support vector machine radiologic-radiomic ML models for classification of renal masses were trained and validated using a 10-fold cross-validation. Performance values for the expert-level radiologists and radiologic-radiomic ML models were compared using the McNemar test. RESULTS. The performance values for the four radiologists were as follows: sensitivity of 73.7-96.8% (median, 84.5%; variance, 122.7%) and specificity of 48.4-71.9% (median, 61.8%; variance, 161.6%) for differentiating ccRCCs from pRCCs and chrRCCs; sensitivity of 73.7-96.8% (median, 84.5%; variance, 122.7%) and specificity of 52.8-88.9% for differentiating ccRCCs from fat-poor angioleiomyolipomas and oncocytomas (median, 80.6%; variance, 269.1%); and sensitivity of 28.1-60.9% (median, 84.5%; variance, 122.7%) and specificity of 75.0-88.9% for differentiating pRCCs and chrRCCs from fat-poor angioleiomyolipomas and oncocytomas (median, 50.0%; variance, 191.1%). After a 10-fold cross-validation, the radiologic-radiomic ML model yielded the following performance values for differentiating ccRCCs from pRCCs and chrRCCs, ccRCCs from fat-poor angioleiomyolipomas and oncocytomas, and pRCCs and chrRCCs from fat-poor angioleiomyolipomas and oncocytomas: a sensitivity of 90.0%, 86.3%, and 73.4% and a specificity of 89.1%, 83.3%, and 91.7%, respectively. CONCLUSION. Expert-level radiologists had obviously large variances in performance for differentiating benign from malignant solid renal masses. Radiologic-radiomic ML can be a potential way to improve interreader concordance and performance.

Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor (CaSR) is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ, 40 mg kg-1 ) in Wistar rats. Animals then received GdCl 3 (an agonist of CaSR, 8.67 mg kg-1 ), NPS-2390 (an antagonist of CaSR, 0.20 g kg-1 ), or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde (MDA), lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH 2 -terminal protein kinase (JNK), p38, and extracellular signaling-regulated kinase (ERK) 1/2. The above parameters could be further increased or aggravated by the administration of GdCl 3 , but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.

Sorafenib, the unique drug as first-line treatment for advanced hepatocellular carcinoma (HCC), has opened a window of hope after searching for effective agents to combat HCC for decades. However, the overall outcomes are far from satisfactory. One of the explanations is the genetic heterogeneity of HCC, which has led to identifying predictive biomarkers for primary resistance to sorafenib, and then applying the concept of personalized medicine, or seeking therapeutic strategies such as combining sorafenib with other anticancer agents. Some of the combinations have demonstrated a better effectiveness than sorafenib alone, with good tolerance. The acquired resistance to sorafenib has also drawn attention. As a multikinase inhibitor, sorafenib targets several cellular signaling pathways but simultaneously or sequentially the addiction switches and compensatory pathways are activated. Several mechanisms are involved in the acquired resistance to sorafenib, such as crosstalks involving PI3K/Akt and JAK-STAT pathways, hypoxia-inducible pathways, epithelial-mesenchymal transition, etc. Based on the investigated mechanisms, some other molecular targeted drugs have been applied as second-line treatment for treat HCC after the failure of sorafenib therapy and more are under evaluation in clinical trials. However, the exact mechanisms accounting for sorafenib resistance remains unclear. Further investigation on the crosstalk and relationship of associated pathways will better our understanding of the mechanisms and help to find effective strategies for overcoming sorafenib resistance in HCC.

Intraoperative blood salvage autotransfusion (IBSA) is used in various surgical procedures. However, because of the risk of reinfusion of salvaged blood contaminated by tumor cells, the use of IBSA in hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) is controversial. The critical points include whether tumor cells can be cleared by IBSA, whether IBSA increases the risk of recurrence or metastasis, and what are the indications for IBSA. Moreover, is it warranted to take the risk of tumor dissemination by using IBSA to avoid allogeneic blood transfusion? Do the remaining tumor cells after additional filtration by leukocyte depletion filters still possess potential tumorigenicity? Does IBSA always work well? We have reviewed the literature and tried to address these questions. The available data indicate that IBSA is safe in LT for HCC, but randomized, controlled and prospective trials are urgently required to clarify the uncertainty.

Using a innovative system consisted of methanogenesis,partial nitritation and anaerobic ammonium oxidation (ANAMMOX) reactors, simultaneous methane production and autotrophic nitrogen removal from domestic sewage was successfully achieved. The results showed that the effluent NH4(+) -N of the combined treatment process was below the detection limit. The effluent NO3(-)-N and NO2(-) -N were less than 0.5 mg x L(-1) and 3.6 mg x L(-1), respectively. The effluent COD of the combined treatment process was 10 mg x L(-1) and a COD removal rate of 98% was achieved. More than 80% COD was removed by the up-flow anaerobic sludge fixed bed (UAFB) and the anaerobic gas production was 3.3 L x d(-1) with a methane yield of 0.3 L x g(-1). About 39.2% of influent COD was removed in form of methane and about 6.52% was transferred to VFAs. Partial nitritation with high nitrite accumulation efficiency of 97% was realized in a Sequencing Batch Reactor (SBR). Ammonium was partly oxidized to nitrite with an ammonium: nitrite ratio of 1: 1.13, which was suitable for the sub-sequent ANAMMOX reaction. In terms of N balance, the N conversion rate of SBR was 36.59% while the anaerobic ammonium oxidation (ANAMMOX) reactor, which was the major system in nitrogen removal, removed 56.91% of N. The TN removal rate of the ANAMMOX reactor was 0.62 kg x (m3 x.d)(-1) and the ratio of NH4(+)-N removal: NO2(-) -N removal: NO3(-) -N generation was 1: 1.18: 1.25. The new process achieves energy recovery by reclaiming methane and autotrophic nitrogen removal by the partial nitritation-ANAMMOX process, and provides a new approach and technology for reforming of domestic wastewater treatment plants.

Objective: To study the protective function and pathophysiology of cystathionine gamma-lyase (CSE)/hydrogen sulfide (H(2)S) system in hepatic ischemia-reperfusion injury (HIRI) in rats., Methods: Wistar rats were randomly distributed into sham group (n = 18), ischemia-reperfusion (IR) group (n = 18), IR + NaHS group (n = 18) and IR + DL-propargylglycine (PAG) group (n = 18). The hepatic IR model was established by Pringle's hepatic vascular occlusion. At each of the indicated time points (1, 3 and 6 hours after IR), the serum levels of H(2)S and the hepatic CSE activity were measured. The serum levels of inflammatory factors, including TNF-α, IL-10 were determined by ELISA methods. The expression of apoptotic protein, TNF-α, in liver tissue was tested by Western blot assay, cell apoptosis was examined by TUNEL and the histological changes were examined in each group., Results: The serum levels of H(2)S and CSE activity were significantly increased in group IR compared with group sham at all indicated time points (P < 0.05). The serum level of inflammatory factors (P < 0.01) and the hepatic expression of TNF-α protein (P < 0.05) were elevated obviously in group IR than that in group sham. Administration of NaHS could reduce the production of inflammatory factors in serum (P < 0.01), inhibit hepatic protein expression of TNF-α (P < 0.05) and attenuate the liver histological scores of IR injury (P < 0.05), whereas PAG aggravated them., Conclusion: The endogenous CSE/H(2)S system maybe involved in the pathogenesis of hepatic IR injury, which suggests that CSE/H(2)S system can protect liver from IR injury in rats by intervening in inflammatory reaction, attenuating the injury severity and inhibiting expression of apoptotic protein TNF-α.

Objective: To investigate whether endostatin, a potent antiangiogenic agent, synergizes with doxorubicin to suppress human hepatocellular carcinoma (HCC)., Methods: An endostatin expression plasmid, Endo-cDNA3.1, was constructed and transfected into COS-1 cells. Human HCC cells of the line HepG2 and human umbilical vein endothelial cells of the line HUVEC were cultured and stimulated by the supernatant of the CoS-1 cells transfected with Endo-pcDNA3.1 and doxorubicin of different concentrations. MTT method was used to detect the proliferation of the cells. (How many) BALB/c mice were inoculated with HepG2 cells to establish HCC models, and then divided into 4 groups to undergo intratumoral injection of pcDNA3.1, End-pcDNA3.1, doxorubicin, or doxorubicin + Endo-pcDNA3.1. Other mice were used as untreated control group. Two weeks later 5 mice from each group were killed with the tumors taken out. Immunostaining was used to calculate the microvessel density and Western blotting was sued to detect the expression of endostatin, hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF)., Results: The proliferation of the HUVEC cells, but not that of the HepG2 cells, transfected with Endo-pcDNA3.1 + doxorubicin was inhibited. Doxorubicin dose-dependently inhibited the proliferation of both HUVEC and HepG2 cells. Endostatin was strongly expressed in the cells treated with Endo-pcDNA3.1 the tumor size of the Endo-pcDNA3.1 and doxorubicin groups were (1545 +/- 180) mm(3) and (953 +/- 250) mm(3) respectively, both significantly lower than that of the untreated and pcDNA3.1 groups [(2360 +/- 330) mm(3) and (2235 +/- 268) mm(3), respectively, all P < 0.01], and the tumor size of the Endo-pcDNA3.1 + doxorubicin group was (426 +/- 87) mm(3), significantly lower than any other groups (all P < 0.01). The number of microvessels of the Endo-pcDNA, doxorubicin, and doxorubicin + Endo-pcDNA3.1 groups were all significantly less than those of the pcDNA3.1 and untreated groups (P < 0.05 or P < 0.01). The expression of HIF-1alphawas downregulated in the Endo-pcDNA3.1 and Endo-pcDNA3.1 + doxorubicin groups, but not in the doxorubicin group. The VEGF expression was down-regulated in the Endo-pcDNA3.1, doxorubicin, and Endo-pcDNA3.1 + doxorubicin groups, especially in the latter., Conclusion: Endostatin gene therapy synergizes with doxorubicin to suppress HCC.

Objective: To construct and purify heme oxygenase-1, GFP gene mediated by recombinant adeno-associated-virus and identify expression rate of GFP in transplanted liver in rats., Methods: Heme oxygenase-1 gene of rat was cloned and subcloned to rAAV vector, the gene sequence was confirmed correct by restriction enzyme and DNA sequencing. The rAAV-HO-1 was then cotransfected into 293 cell line with accessory plasmid virus helper and AAV-cap-rep through CaCl2 coprecipitation. Virus particles were purified by heparin column chromatography and titre were detected by Real-time PCR. An orthotopic liver transplantation model by Wistar to Wistar was set up using Kamada's two cuff technique. Purified rAAV-GFP was injected into portal vein and incubated for 2 hours at the donor liver cold preserved stage, and then performed OLT. Recipients were killed and visceral organs were sampled at 1 and 3 months after operation respectively, frozen section (3-5 microm) were prepared and gene expression rate in different tissues was examined under fluorescence microscope., Results: The inserted segment of HO-1 was identified through restriction enzyme cutting followed with electrophoresis, the result of DNA sequencing was in accordance with which found in Genbank. The GFP expression rate was over 80% in allograft at 1 and 3 month after transfection whereas there was no GFP expression in heart, lung, spleen, kidney and small bowel., Conclusions: High titre rAAV carried HO-1 and GFP were constructed successfully. Steady and effective expression of GFP mediated by rAAV was demonstrated in liver allograft in rats.

Objective: To investigate the effects of oxymatrine on protecting the liver against ischemia-reperfusion injury (IRI) and explore the mechanism thereof., Methods: Thirty male Wistar rats were randomly divided into 3 equal groups: IRI group (2 ml normal saline was injected into the dorsal vein of penis, 30 min later laparotomy was performed, arterial clamp was used to grip the hepatic artery and portal vein for 30 minutes and then removed, the vessels were reperfused for 90 min, and 4 ml blood was collected from the aorta; parts of the liver were resected); oxymatrine group (oxymatrine 40 mg/kg was injected into the dorsal vein of penis, and the other procedures were the same as in the IRI group); and sham operation group (2 ml normal saline was injected into the dorsal vein of penis, laparotomy was performed, 150 min after the injection 4 ml blood was collected from the aorta and parts of the liver were resected). The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected. The liver tissues underwent HE staining and TUNEL staining for pathological examination. Suspension of single hepatocytes was prepared to observe the ratio of apoptotic cells and cell cycles by flow cytometry (FCM). Western blotting was used to examine the Fas protein expression., Results: The AST and ALT levels of the IRI group were 1326 U/L +/- 211 U/L and 768 U/L +/- 175 U/L respectively, significantly higher than those of the sham operation group (112 U/L +/- 53 U/L and 55 U/L +/- 17 U/L, both P < 0.05) and those of the oxymatrine group (513 U/L +/- 96 U/L and 352 U/L +/- 72 U/L respectively, both P < 0.01). The liver cells of the sham operation group were normal, those of the IRI group showed remarkable edema and cytoplasm degeneration. TUNEL staining showed remarkably more apoptotic cells in the IRI group. FCM showed that the apoptotic rate of hepatocytes was 42.8% +/- 5.2% in the IRI group, significantly higher than in the oxymatrine group (8.8% +/- 1.8%, P < 0.01), and that the ratio of hepatocytes in G(0)/G(1) stage of the IRI group was 99.2% +/- 1.8%, significantly higher than that of the sham operation group (77.0% +/- 2.1%), and that of the oxymatrine group (87.6% +/- 2.8%) (both P < 0.05); the ratio of hepatocytes in the S stage of the IRI group was 0.52% +/- 0.25%, significantly lower than those of the sham operation group (23.94% +/- 1.84%) and oxymatrine group (12.42% +/- 0.46%) (both P < 0.01). The Fas protein expression was significantly highly in the IRI group than in the oxymatrine group., Conclusion: Remarkably reducing the IRI of hepatocytes, oxymatrine has potential to protect the liver against IRI during surgical intervention.

Objective: To investigate the synergistic effects of antisense HIF-1alpha gene therapy combined with B7-1-mediated immunotherapy on cancer treatment., Methods: Antisense HIF-1alpha and B7-1 expression vector were constructed. Lymphoma cells EL-4 were injected subcutaneously into C57BL/6 mice and transplanted lymphomas were established. The mice received either antisense HIF-1alpha, B7-1, or a combinational agent, complexed with DOTAP cationic liposomes. The tumor growth in the mice was monitored. Expression of HIF-1alpha, B7-1 and VEGF were detected by immunohistochemistry and Western blotting. The tumor blood vessels were immunostained with CD31- antibodies and the tumor vascular density was assessed by light microscopy., Results: Gene transfer of plasmid expressing the encoded antisense HIF-1alpha inhibited VEGF expression and reduced vascular density in the tumors, eradicated tumors in diameter smaller than 0.1 cm and only retarded the growth of larger tumors. Whereas combination of antisense HIF-1alpha gene therapy and B7-1 immunotherapy eradicated all tumors in diameter of 0.4 cm., Conclusion: Antisense HIF-1alpha blocks tumor hypoxia pathway by downregulating VEGF expression, reduction of vascular density and enhances B7-1-mediated immunotherapy. Strategies that target HIF-1 may have therapeutic potential in cancer treatment and are worthy of further studying.

Objective: To explore the effect of von Hippel-Lindau(VHL) gene on growth of EL-4 solid tumors in vivo., Methods: C57BL/6 mice model of solid tumors was established by subcutaneous injection of EL-4 lymphoma cells. Mice were randomly divided into two groups as treatment group (n=6) and control group (n=6) when tumor diameter increased to 0.1 cm and 0.4 cm respectively. Plasmid pcDNA3-VHL was injected into solid tumor in treatment group, empty pcDNA3 vector in control group. The growth of tumor was observed. Immunohistochemistry and Western blot analysis were used to examine the transgenic expression of VHL, hypoxia inducible factor-1alpha (HIF)-1alpha, bcl-2 and VEGF. Microvessel density (MVD) and apoptosis index (AI) of tumors were also detected., Results: VHL gene transfer eradicated tumors with small size (0.1 cm diameter), but it only retarded the growth of large tumors (0.4 cm diameter). VHL was overexpressed, the expression levels of VEGF, HIF-1alpha and bcl-2 were reduced in treatment group compared with those in the control group. The level of MVD was significantly lower in treatment group (P< 0.05), but AI was higher in treatment group compared with those in the control group (P< 0.01)., Conclusion: VHL gene therapy can inhibit the growth of EL-4 solid tumor in vivo.