Application of contrast-enhanced ultrasound in diagnosis and grading of bladder urothelial carcinoma.

PURPOSE: To explore the application of contrast-enhanced ultrasound (CEUS) for the diagnosis and grading of bladder urothelial carcinoma (BUC). METHODS: The results of a two-dimensional ultrasound, color Doppler ultrasound and CEUS, were analyzed in 173 bladder lesion cases. The ultrasound and surgical pathology results were compared, and their diagnostic efficacy was analyzed. RESULTS: There were statistically significant differences between BUC and benign lesions in terms of color blood flow distribution intensity and CEUS enhancement intensity (both P < 0.05). The area under the time-intensity curve (AUC), rising slope, and peak intensity of BUC were significantly higher than those of benign lesions (all P < 0.05). The H/T (height H / basal width T)value of 0.63 was the critical value for distinguishing high- and low-grade BUC, had a diagnostic sensitivity of 80.0% and a specificity of 60.0%. CONCLUSION: The combination of CEUS and TIC can help improve the diagnostic accuracy of BUC. There is a statistically significant difference between high- and low-grade BUC in contrast enhancement intensity (P < 0.05); The decrease of H/T value indicates the possible increase of the BUC grade.

Prognostic value of obesity in patients with cancer treated with immune checkpoint inhibitors: An updated meta­analysis and systematic review.

Accumulating interest has been surging over the past few years regarding the effects of obesity on immunotherapy. In addition to the body mass index (BMI), imaging-quantified body fat compartments have been investigated. The present study aimed to evaluate the predictive value of the BMI and computed tomography (CT)-based body fat in patients with cancer receiving immunotherapy. For this purpose, the PubMed, MEDLINE, EMBASE and Cochrane databases were searched from January 2017 to July 2022. Clinical studies evaluating the association between BMI or body fat and survival of patients with cancer treated with immune checkpoint inhibitors (ICIs) were included. In total, 15 studies reporting on the BMI were included in the meta-analysis and 16 studies evaluating body fat were included in the systematic review. According to the classification of the World Health Organization, overweight and obese patients with ICI treatment showed improved overall survival [overweight vs. normal: Hazard ratio (HR)=0.79, 95% confidence interval (CI)=0.64-0.98, P=0.03; obese vs. normal: HR=0.75, 95% CI=0.60-0.94, P=0.013] and progression-free survival (overweight vs. normal: HR=0.82, 95% CI=0.70-0.97, P=0.02; obese vs. normal: HR=0.81, 95% CI=0.65-1.02, P=0.07). Among the articles investigating the effect of body fat composition on the efficacy of immunotherapy, a number of studies included various CT analysis techniques and cutoffs to define body fat composition. Associations of body fat with survival were contradictory in different patients with cancer treated with immunotherapy. Obesity was associated with better survival in patients with cancer treated with ICIs. Further analyses are required to demonstrate the prognostic value of body fat in patients with cancer immunotherapy.

[Simulation of carbon sequestration and timber production in Larix olgensis plantation based on CO2FIX model]. / 基于CO2FIX模型的长白落叶松人工林碳汇和木材生产模拟.

Based on datasets from plot survey and bibliographic of Larix olgensis plantations in Maoer Mountain, the CO2FIX model was used to quantitatively simulate the effects of different rotations (30, 40, 50, 60 years), site indices (12, 16, 20 m), and initial densities (2500, 3333, 4444 trees·hm-2) on the stand level carbon flows among different carbon pools (i.e., biomass carbon pool, soil carbon pool, and product carbon pool). The results showed that the CO2FIX model had high reliability for simulating the processes of L. olgensis plantation, with the average relative errors of stand biomass and volume between analog and measured values being 6.4% and 3.7%. Under the baseline conditions of initial density of 3333 trees·hm-2, site index of 16 m and rotation of 40 years, the carbon stock of total and sub-pool of L. olgensis plantation changed periodically with rotation. The total stand carbon stock and volume for L. olgensis plantation increased with the extension of rotation, the improvement of site index, and the increase of initial density. The stand carbon stock and volume would be increased by 12.2% and 31.2%, 36.7% and 67.8%, respectively, when the reference rotation was correspondingly extended by 10 and 20 years. However, if the reference rotation was shortened by 10 years, stand carbon stock and volume would be correspondingly decreased by 20.9% and 40.4%, respectively. When the initial density was set as 3333 and 4444 trees·hm-2, stand carbon stock and volume were increased by 27.8% and 50.9%, 27.4% and 49.1%, respectively. When the site index was under the range of 12 to 20 m, stand carbon stock and volume could be increased by 36.0% and 40.3%, 39.3% and 44.2%, respectively, with each increase of 4 m in site index. During one rotation, 271.57 t C per hectare could be fixed into L. olgensis plantation. At the end round of the rotation, 27.47 and 56.75 t C were transferred to soil and wood product carbon pools. Therefore, when the site condition was good, the management model with a higher initial density (4444 trees·hm-2) and longer rotation (60 years) would be more beneficial to maximizing the carbon sink and timber benefits of L. olgensis plantation.

Modeling Kaempferol as a Potential Pharmacological Agent for COVID-19/PF Co-Occurrence Based on Bioinformatics and System Pharmacological Tools.

Objective: People suffering from coronavirus disease 2019 (COVID-19) are prone to develop pulmonary fibrosis (PF), but there is currently no definitive treatment for COVID-19/PF co-occurrence. Kaempferol with promising antiviral and anti-fibrotic effects is expected to become a potential treatment for COVID-19 and PF comorbidities. Therefore, this study explored the targets and molecular mechanisms of kaempferol against COVID-19/PF co-occurrence by bioinformatics and network pharmacology. Methods: Various open-source databases and Venn Diagram tool were applied to confirm the targets of kaempferol against COVID-19/PF co-occurrence. Protein-protein interaction (PPI), MCODE, key transcription factors, tissue-specific enrichment, molecular docking, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to clarify the influential molecular mechanisms of kaempferol against COVID-19 and PF comorbidities. Results: 290 targets and 203 transcription factors of kaempferol against COVID-19/PF co-occurrence were captured. Epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase SRC (SRC), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 8 (MAPK8), RAC-alpha serine/threonine-protein kinase (AKT1), transcription factor p65 (RELA) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) were identified as the most critical targets, and kaempferol showed effective binding activities with the above critical eight targets. Further, anti-COVID-19/PF co-occurrence effects of kaempferol were associated with the regulation of inflammation, oxidative stress, immunity, virus infection, cell growth process and metabolism. EGFR, interleukin 17 (IL-17), tumor necrosis factor (TNF), hypoxia inducible factor 1 (HIF-1), phosphoinositide 3-kinase/AKT serine/threonine kinase (PI3K/AKT) and Toll-like receptor signaling pathways were identified as the key anti-COVID-19/PF co-occurrence pathways. Conclusion: Kaempferol is a candidate treatment for COVID-19/PF co-occurrence. The underlying mechanisms may be related to the regulation of critical targets (EGFR, SRC, MAPK3, MAPK1, MAPK8, AKT1, RELA, PIK3CA and so on) and EGFR, IL-17, TNF, HIF-1, PI3K/AKT and Toll-like receptor signaling pathways. This study contributes to guiding development of new drugs for COVID-19 and PF comorbidities.

Development of chloroplast microsatellite markers for Glyptostrobus pensilis (Cupressaceae).

PREMISE: Glyptostrobus pensilis (Cupressaceae) is a critically endangered conifer native to China, Laos, and Vietnam, with only a few populations remaining in the wild. METHODS AND RESULTS: Using a complete chloroplast genome sequence, we designed 70 cpSSR loci and tested them for amplification success and polymorphism in 16 samples. Ten loci were found to be polymorphic and their genetic diversity was characterized using a total of 83 individuals from three populations in China. A total of 43 haplotypes were present, the effective number of haplotypes varied from 4.55 to 13.36, and the haplotypic richness ranged from 8.04 to 16.00. Gene diversity ranged from 0.81 to 0.97 (average 0.89). The number of alleles per locus and population ranged from one to eight, and the effective number of alleles ranged from 1.00 to 3.90. All polymorphic loci were successfully amplified in the related species Cryptomeria japonica var. sinensis, Taxodium distichum, T. ascendens, and Cunninghamia lanceolata. CONCLUSIONS: These newly developed chloroplast microsatellites will be useful for population genetic and phylogeographic analyses of G. pensilis and related species.

Effect of fatty liver background on contrast-enhanced ultrasonographic appearance of focal nodular hyperplasia.

BACKGROUND: Focal nodular hyperplasia (FNH) is increasingly diagnosed as a result of the advances in imaging studies such as contrast-enhanced ultrasonography (CEUS), enhanced computed tomography and magnetic resonance imaging. However, FNH with atypical features can be difficult to differentiate from other benign and malignant tumors. The aim of this study was to investigate the influence of fatty liver background on the CEUS characteristics of FNH. METHODS: Twenty-six patients with FNH were divided into two groups: group A included 14 patients with fatty liver and group B included 12 patients with normal liver background. Conventional two-dimensional ultrasonography and color Doppler flow imaging (CDFI) were conducted and followed by real-time dual-frame CEUS. RESULTS: On two-dimensional ultrasonography, hypo-echoic nodules were present in most of the patients in group A (12/14) and hyperechoic nodules in most of those in group B (7/12). The difference in the nodule echotextures between the two groups was statistically significant (P<0.05). Nodules with centrifugal blood flow signals on CDFI were found in 6 of the 14 patients in group A and 5 of the 12 in group B (P>0.05). On CEUS, nodules with a central spoked-wheel-like enhancement pattern in the early arterial phase were observed in 8 patients in group A and those with an eccentric enhancement pattern in the remaining 6 patients. In this group, 3 patients had hypoechoic nodules in the delayed phase. Eleven of the 14 patients in this group were diagnosed accurately with CEUS. In group B, nodules with a rapid central spoked-wheel-like enhancement pattern in the early arterial phase were found in 8 patients by CEUS and those with rapid an eccentric enhancement pattern in 4. The nodules were found to be continuously enhanced in the delayed phase. All of the patients in group B were accurately diagnosed with CEUS. CONCLUSIONS: A FNH nodule on a background of fatty liver may present a hypoechoic pattern on two-dimensional ultrasonography and a hypoechoic wash-out pattern in the delayed phase on CEUS. At this time, punch biopsy is needed for the diagnosis or differential diagnosis of FNH.

Ultrasound-guided fine needle aspiration biopsy in differential diagnosis of portal vein tumor thrombosis.

BACKGROUND: Portal vein tumor thrombosis (PVTT) is a serious complication and a major metastatic way of hepatocellular carcinoma(HCC). But portal vein benign thrombosis(PVBT) always appears in patients with hepatocirrhosis, and PVTT should be differentiated from PVBT. The aim of this study was to probe the value of ultrasound-guided fine needle aspiration biopsy in differential diagnosis of PVTT. METHODS: Twenty-two HCC patients with portal vein thrombosis and 8 hepatocirrhosis patients with portal vein thrombosis were studied by ultrasound-guided fine needle aspiration biopsy. Twelve portal vein thrombosis filling portal vein embranchment of the 30 portal vein thrombosis patients were examined by 18G automatic biopsy. The positive rates of aspiration biopsy cytology and histology were calculated and compared with those of automatic biopsy. RESULTS: The positive rates of fine needle aspiration biopsy cytology and histology were 93.3% (28/30) and 90.0% (27/30), respectively. They were not different markedly from that of automatic biopsy 91.7% (11/12). In aspiration biopsy of 22 HCC patients with PVTT, HCC cellular was found in 19 portal vein thrombosis patients (86.4%) by cytology examination and in 18 portal vein thrombosis patients (81.8%) by histology examination. In total, 20 tumor thrombi were detected. The other two were diagnosed as benign thrombosis. No HCC cell and/or tissue was observed in 8 patients with hepatocirrhosis associated with portal vein thrombosis. CONCLUSIONS: Ultrasound-guided fine needle biopsy in detecting PVTT shows a high positive rate and is of diagnostic value. The positive rate is not apparently different from that of automatic biopsy. Hence the case that fails to be diagnosed by color Doppler flow imaging(CDFI) and pulsed Doppler can be detected early by ultrasound-guided fine needle aspiration biopsy.

Experimental and clinical assessment of percutaneous hepatic quantified ethanol injection in treatment of hepatic carcinoma.

AIM: To detect the relationship between absolute ethanol injection quantity, the interval and formation of fibreboard, the curative effect in treatment of hepatocarcinoma and to evaluate the clinical application of percutaneous hepatic quantified ethanol injection (PHQEI) in treatment of hepatic carcinoma (HCC). METHODS: (1) Experimental study: Twenty-four human hepatic carcinoma SMMC-7721 xenografted nude mice were randomly divided into three groups: group A injected with quantified ethanol at short intervals (QESI), group B with quantified ethanol at long intervals (QELI) and group C with a small quantity of ethanol at long intervals (SQLI). The tumor tissues were sent for patho-histology and electron microscopic examinations. The diameters of tumors were measured with high frequency ultrasound before and after therapies and tumor growth index (TGI) was calculated. (2) Clinical study: Tumors of 122 cases of pathologically proved HCC were injected with quantified ethanol guided by ultrasound every 3-5 d 4-10 times per period of treatment. The quantity of ethanol was calculated according to the regressive equations where Y = 2.885X when the mass was < or =5 cm in diameter and Y = 1.805X when the mass was >5 cm in diameter (X is the maximal diameter of the mass with the unit cm, Y is the ethanol quantity with the unit mL). The survival rates of 1, 2, 3 and 4 years and recurrent rates in situ as well as dystopia in the liver were calculated. RESULTS: (1) Experimental study: TGI of QESI group (0.072+/-0.018) and QELI group (0.094+/-0.028) was apparently lower than that of SQLI group (1.982+/-0.482) (P<0.01). TGI of QESI group seemed to be lower than that of QELI group, but it was not markedly different (P>0.05) between two groups. Severe degeneration and necrosis could be seen in QESI group by patho-histology examination. Coagulative necrosis could be seen in most tumors of QESI group and there were no residual cancer cells under electronic microscope, while the residual cancer and inflammatory cells and fibre tissues could be seen around the tumors of QELI group. Infiltration of inflammatory cells could be seen and fibre tissues were formed. (2) Clinical study: B mode ultrasound showed that 62.5% of tumors shrank after PHQEI. The survival rates of 1, 2, 3 and 4 years of the group with tumors < or =3 cm in diameter were higher than those of the group with tumors >3 cm in diameter. The recurrent rates of tumors in situ of the former group were apparently lower than those of the latter group. The recurrent rates of tumors in dystopia in the liver of the former group were markedly lower than those of the latter group. The 122 cases underwent a total of 1221 PEI. There were no complications such as hemorrhage and severe heart, liver and kidney functional injuries except for 1 case of melena and 4 cases of jaundice who recovered after 1-2 wk under common therapies. CONCLUSION: The experimental study shows quantified ethanol at intervals of 3-5 d could improve the curative effect of hepatocarcinoma. The clinical study shows PHQEI is an effective therapeutic method for HCC with few side-effects, and a low-cost. The treatment efficacy is more remarkable for tumors < or =3 cm in diameter.

Biological characteristics of HCC by ultrasound-guided aspiration biopsy and its clinical application.

AIM: To probe the pathological biological characteristics of hepatocellular carcinoma (HCC) by the ultrasound-guided aspiration biopsy and assess the clinical application value of this method. METHODS: The biopsy and DNA analysis by flow cytometry (FCM) were taken in 46 cases with HCC nodules, including 26 cases and 20 cases with nodules < or =3 cm and >3 cm in diameters respectively, and 12 cases with intrahepatic benign hyperplastic nodules. They were taken in 22 cases of 46 cases with HCC before and after the therapy. Fine-needles and automatic histological incised biopsy needles were used. The fresh biopsy tissue was produced into the single cell suspension, which was sent for DNA detection and ratio analysis of cell period. The ratio of each DNA period of cell proliferation of each group was calculated and compared with each other. The DNA aneuploid (AN) and apoptosis cell peak were observed and their percentages were calculated. RESULTS: The ratios of S and G(2)/M periods of DNA, which reflect cell hyperproliferation, in the group with HCC tumors >3 cm in diameter were markedly higher than those of the group with HCC nodules < or =3 cm in diameter and the group with the benign hyperplastic nodules (P<0.01 except A:B of S period, P<0.05). The ratios of the middle group were also apparently higher than those of the latter group (P<0.01). The ratio of DNA AN of 46 cases with HCC nodules was 34.8 % (16/46). None of the cases with the intrahepatic hyperplastic nodules appeared AN. The DNA AN appeared more apparently with the growth of the tumors. The AN ratio of the group with tumors >3 cm in diameter was 55 % (11/20), markedly higher than that of the group with tumors < or =3 cm in diameter which was 19.2 % (5/26) (P<0.01). The FCM DNA analysis of 22 specimens of hepatic carcinoma tissue before therapy showed that the aneuploid peaks appeared in 5 cases (22.7 %). The ratio of G(1) period rose after therapy while the S period and G(2)/M ratios fell (P<0.01). The aneuploid peak disappeared in the 5 cases after the therapy, while the apoptosis peaks in 12 cases (54.5 %) appeared. CONCLUSION: Addition to supply the information of the pathological morphology of the tumor, the ultrasound-guided fine-needle aspiration tissue could be sent for FCM DNA analysis to comprehend its pathological biological characteristics. This can not only provide the clinic the reliable information about the occurrence, development, diagnosis, curative effect and prognosis of tumors but also supply biological information for clinic to choose therapeutic schemes.