Size effects and electronic properties of zinc-doped boron clusters Zn B n (n = 1-15).

CONTEXT: To gain a deeper understanding of zinc-doped boron clusters, theoretical calculations were performed to investigate the size effects and electronic properties of zinc-doped boron clusters. The study of the electronic properties, spectral characteristics, and geometric structures of Zn B n (n = 1-15) is of great significance in the fields of semiconductor materials science, material detection, and improving catalytic efficiency. The results indicate that Zn B n (n = 1-15) clusters predominantly exhibit planar or quasi-planar structures, with the Zn atom positioned in the outer regions of the B n framework. The second stable structure of Zn B 3 is a three-dimensional configuration, indicating that the structures of zinc-doped boron clusters begin to convert from the planar or quasi-planar structures to the 3D configurations. The second low-energy structure of Zn B 15 is a novel configuration. Relative stability analyses show that the Zn B 12 has better chemical stability than other clusters with a HOMO-LUMO gap of 2.79 eV. Electric charge analysis shows that part electrons on zinc atoms are transferred to boron atoms, and electrons prefer to cluster near the B n framework. According to the electron localization function, it gets harder to localize electrons as the equivalent face value drops, and it's challenging to see covalent bond formation between zinc and boron atoms. The spectrograms of Zn B n (n = 1-15) exhibit distinct properties and notable spectral features, which can be used as a theoretical basis for the identification and confirmation of boron clusters doped with single-atom transition metals. METHODS: The calculations were performed using the ABCluster global search technique combined with density functional theory (DFT) methods. The selected low-energy structures were subjected to geometric optimization and frequency calculations at the PBE0/6-311 + G(d) level to ensure structural stability and eliminate any imaginary frequencies. To acquire more precise relative energies, we performed single-point energies calculations for the low-lying isomers of Zn B n (n = 1-15) at the CCSD(T)/6-311 + G(d)//PBE0/6-311 + G(d) level of theory. All calculations were performed using Gaussian 09 software. To facilitate analysis, we utilized software tools such as Multiwfn, and VMD.

Age-Dependent Female Survival Advantage in Hepatocellular Carcinoma: A Multicenter Cohort Study.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has a higher incidence in males, but the association of sex with survival remains controversial. This study aimed to examine the effect of sex on HCC survival and its association with age. METHODS: Among 33,238 patients with HCC from 12 Chinese tertiary hospitals, 4175 patients who underwent curative-intent hepatectomy or ablation were analyzed. Cancer-specific survival (CSS) was analyzed using Cox regression and Kaplan-Meier methods. Two propensity score methods and multiple mediation analysis were applied to mitigate confounding. To explore the effect of estrogen, a candidate sex-specific factor that changes with age, female participants' history of estrogen use, and survival were analyzed. RESULTS: There were 3321 males and 854 females included. A sex-related disparity of CSS was present and showed a typical age-dependent pattern: a female survival advantage over males appeared at the perimenopausal age of 45 to 54 years (hazard risk [HR], 0.77; 5-year CSS, 85.7% vs 70.6%; P = .018), peaked at the early postmenopausal age of 55 to 59 years (HR, 0.57; 5-year CSS, 89.8% vs 73.5%; P = .015), and was not present in the premenopausal (<45 y) and late postmenopausal groups (≥60 y). Consistent patterns were observed in patients after either ablation or hepatectomy. These results were sustained with propensity score analyses. Confounding or mediation effects accounted for only 19.5% of sex survival disparity. Female estrogen users had significantly longer CSS than nonusers (HR, 0.74; 5-year CSS, 79.6% vs 72.5%; P = .038). CONCLUSIONS: A female survival advantage in HCC depends on age, and this may be associated with age-dependent, sex-specific factors.

A multicenter retrospective cohort study on the attributable risk of patients with Acinetobacter baumannii sterile body fluid infection / 中国感染控制杂志

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Hepatocellular Carcinoma ≤5 cm: Biological Characteristics and Patient Outcomes.

Introduction: The present study aimed to evaluate the influence of biological characteristics of hepatocellular carcinoma (HCC) on the Liver Imaging Reporting and Data System (LI-RADS) v2017 category of contrast-enhanced ultrasound (CEUS) in patients with high risk and compare the outcomes among different categories after radical resection. Methods: Between June 2017 and December 2020, standardized CEUS data of liver nodules were prospectively collected from multiple centers across China. We conducted a retrospective analysis of the prospectively collected data on HCCs measuring no more than 5 cm, as diagnosed by pathology. LI-RADS categories were assigned after thorough evaluation of CEUS features. Then, CEUS LI-RADS categories and major features were compared in different differentiation, Ki-67, and microvascular invasion (MVI) statuses. Differences in recurrence-free survival (RFS) among different LI-RADS categories were further analyzed. Results: A total of 293 HCC nodules in 293 patients were included. This study revealed significant differences in the CEUS LI-RADS category of HCCs among differentiation (p < 0.001) and levels of Ki-67 (p = 0.01) and that poor differentiation (32.7% in LR-M, 12% in LR-5, and 6.2% in LR-4) (p < 0.001) and high level of Ki-67 (median value 30%) were more frequently classified into the LR-M category, whereas well differentiation (37.5% in LR-4, 15.1% in LR-5, and 11.5% in LR-M) and low levels of Ki-67 (median value 11%) were more frequently classified into the LR-4 category. No significant differences were found between MVI and CEUS LI-RADS categories (p > 0.05). With a median follow-up of 23 months, HCCs assigned to different CEUS LI-RADS classes showed no significant differences in RFS after resection. Conclusions: Biological characteristics of HCC, including differentiation and level of Ki-67 expression, could influence major features of CEUS and impact the CEUS LI-RADS category. HCCs in different CEUS LI-RADS categories showed no significant differences in RFS after resection.

Novel homozygous ADAMTS17 missense variant in Weill-Marchesani syndrome.

AIM: To explore the phenotype and genotype of Weill-Marchesani syndrome (WMS) in a Chinese family and review related literature. METHODS: Three WMS patients and other unaffected individuals in this family with a history of consanguineous marriage were included in this study. Medical history, comprehensive ophthalmic examinations, and systemic evaluation, as well as whole exome and Sanger sequencing of specific genomic regions, were performed. RESULTS: The three affected siblings presented with short stature, brachydactyly and ocular disorders, including very shallow anterior chamber, high myopia, microspherophakia lens subluxation with stretched zonules and glaucoma. Genetic analysis verified a homozygous missense mutation (c.2983C>T: p. Arg995Trp) in ADAMTS17, which was correlated with the diseases in this family, indicating an autosomal recessive inherited manner of WMS. This review aims to summarize the mutation sites of WMS genes, so as to prevent the disease and better guide clinical diagnosis and treatment. CONCLUSION: A novel homozygous missense variant of ADAMTS17 is identified in a WMS family with a history of consanguineous marriage. Our study expands the range of mutations associated with WMS and deepens our understanding of pathology in disease associated with ADAMTS17 variants.

Clinical report and genetic analysis of a child with Aicardi-Goutières syndrome type 3 due to compound heterozygous variants of RNASEH2C gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a child with Aicardi-Goutières syndrome 3 (AGS3).@*METHODS@#Trio whole exome sequencing was carried out for the child and his parents, and candidate variants were verified by Sanger sequencing. To further clarify their pathogenicity, the crystal structure of the variants was simulated and analyzed, and the plasmid of variants was expressed in vitro. A literature search was also carried out to summarize the phenotypic and genetic characteristics of AGS3.@*RESULTS@#The child was found to harbor novel compound heterozygous variants of the RNASEH2C gene, namely c.434G>T (p.Arg145Leu) and c.494G>C (p.Ter165Ser), which were inherited from his mother and father, respectively. Analysis of protein crystal structure suggested that the c.434G>T (p.Arg145Leu) variant may affect the stability of local structure, and in vitro experiments showed that this variant can lead to protein degradation. The c.494G>C (p.Ter165Ser) variant has destroyed the stop codon, resulting in prolonged variant.@*CONCLUSION@#The novel compound heterozygous variants of the RNASEH2C gene probably underlay the AGS3 in this child, which has enriched the phenotypic and mutational spectrum of this disorder.

Diagnosis and treatment of 18 cases of Chiari malformation with hoarseness / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the diagnosis and treatment of Chiari malformation patients with hoarseness and other otorhinolaryngological symptoms. Methods: The clinical data of 18 patients of Chiari malformation with hoarseness were retrospectively collected, which was composed of 5 men and 13 women, aged 3-71 with median age of 52. All the patients were admitted to the Affiliated Hospital of Qingdao University from January 1989 to January 2020. All patients underwent brain MRI and laryngoscopy. The patient's symptoms and first diagnosis department, diagnosis time, total course of disease, hoarseness course, diagnosis and treatment, and postoperative recovery time were summarized. Follow-up time was 3-16 years, with median follow-up time of 6.5 years. Descriptive methods were used for analysis. Results: The first visit departments of 18 patients included neurology (9 cases), otorhinolaryngology head and neck surgery (5 cases), pediatrics (2 cases), orthopedics (1 case) and respiratory department (1 case). Except for the 7 cases in neurology department, the other 11 patients were not diagnosed in time. The disease duration of 18 patients with Chiari malformation ranged from 2 months to 5 years, and hoarseness was present from 20 days to 5 years. After diagnosis, 9 patients underwent posterior fossa decompression surgery, and 1 of them underwent syrinx drainage at the same time. The symptoms of 8 cases improved significantly after operation, with the improvement time from 1 to 30 days. In addition, 9 patients chose conservative treatment, among whom 8 had no improvement in symptoms and 6 progressed. Conclusions: Posterior fossa decompression is an effective treatment for Chiari malformation, and the prognosis is good. Timely diagnosis and treatment can improve the prognosis of patients.

Morphologic and functional changes of ventricles between pre- and post- cone reconstruction surgery in children with Ebstein’s anomaly / 中华胸心血管外科杂志

Objective:To understand the morphologic and functional changes of ventricles between pre- and post- cone reconstruction(CR) surgery in children with Ebstein’s anomaly(EA).Methods:The clinical data of children with EA who underwent CR and cardiac magnetic resonance(CMR) in Shanghai Children’s Medical Center between July 2011 to April 2019 were collected and analyzed. Ventricular functions were assessed with the use of ejection fraction(EF), stroke volume index(SVI), cardiac output(CO), and cardiac index(CI). Ventricular morphologies were assessed with the use of end-diastolic ventricular volume(EDV), end-diastolic ventricular volume index(EDVI) and ventricular cine images. Paired student t tests and Wilcoxon rank sum tests were used for statistical analysis. Results:There were a total of 32 children with EA who underwent CR and CMR, with 13 males and 19 females, a median operative age of 2.9 years old(0.6-15.5 years old), and a mean follow-up time of(4.4±1.9) years. Seven patients had both preoperative and postoperative CMR, with a mean follow-up time of(3.3±1.4) years; Eleven patients had two or more postoperative CMR, with a mean interval time of(1.9±1.0) years. After the surgery, the median tricuspid-regurgitation grade decreased from 3 to 2, and the median New York Heart Association functional class improved from 2.5 to 1, the left ventricle(LV)-SVI, LV-EDV and LV-EDVI increased from 29.8 ml/m 2 to 43.2 ml/m 2( P=0.039), from 56.4 ml to 86.9 ml( P=0.004), from 50.5 ml/m 2 to 68.4 ml/m 2( P=0.022), respectively. And the long-term LV-EDV increased from 56.6 ml to 74.7 ml( P=0.002) when compared to that of early postoperative. There was no significant differences in right ventricle(RV)-EF, RV-SVI, RV-CO, RV-CI, RV-EDV and RV-EDVI between pre- and post- CR( P>0.05); but the long-term postoperative RV-CO and RV-EDV increased from 3.1 L/min to 4.1 L/min( P=0.008), from 67.5 ml to 96.5 ml( P<0.001), respectively, when compared with those of early postoperative. Conclusion:CR improves the function and morphology of both ventricles in children with EA. And although postoperative ventricles grow well, RV dysfunction persists.

Therapeutic Mechanism of Kai Xin San on Alzheimer's Disease Based on Network Pharmacology and Experimental Validation / 中国结合医学杂志

OBJECTIVE@#To explore the specific pharmacological molecular mechanisms of Kai Xin San (KXS) on treating Alzheimer's disease (AD) based on network pharmacology and experimental validation.@*METHODS@#The chemical compounds of KXS and their corresponding targets were screened using the Encyclopedia of Traditional Chinese Medicine (ETCM) database. AD-related target proteins were obtained from MalaCards database and DisGeNET databases. Key compounds and targets were identified from the compound-target-disease network and protein-protein interaction (PPI) network analysis. Functional enrichment analysis predicted the potential key signaling pathways involved in the treatment of AD with KXS. The binding affinities between key ingredients and targets were further verified using molecular docking. Finally, the predicted key signaling pathway was validated experimentally. Positioning navigation and space search experiments were conducted to evaluate the cognitive improvement effect of KXS on AD rats. Western blot was used to further examine and investigate the expression of the key target proteins related to the predicted pathway.@*RESULTS@#In total, 38 active compounds and 469 corresponding targets of KXS were screened, and 264 target proteins associated with AD were identified. The compound-target-disease and PPI networks identified key active ingredients and protein targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested a potential effect of KXS in the treatment of AD via the amyloid beta (A β)-glycogen synthase kinase-3 beta (GSK3 β)-Tau pathway. Molecular docking revealed a high binding affinity between the key ingredients and targets. In vivo, KXS treatment significantly improved cognitive deficits in AD rats induced by Aβ1-42, decreased the levels of Aβ, p-GSK3β, p-Tau and cyclin-dependent kinase 5, and increased the expressions of protein phosphatase 1 alpha (PP1A) and PP2A (P<0.05 or P<0.01).@*CONCLUSION@#KXS exerted neuroprotective effects by regulating the Aβ -GSK3β-Tau signaling pathway, which provides novel insights into the therapeutic mechanism of KXS and a feasible pharmacological strategy for the treatment of AD.

Period-Dependent Survival Benefit of Percutaneous Microwave Ablation for Hepatocellular Carcinoma: A 12-Year Real-World, Multicentric Experience.

Introduction: Although microwave ablation (MWA) is a promising technique for hepatocellular carcinoma (HCC) treatment, its 10-year efficacy is unknown. Objective: The objective of the study was to assess whether the advances in MWA for HCC translated into a real-world survival benefit. Methods: This retrospective study included 2,354 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 to B from 5 hospitals, with at least 2 years of follow-up for all the patients. Recurrence and survival were analyzed using the Kaplan-Meier method with time-period stratification. Results: A total of 5,326 HCCs (mean diameter, 2.9 cm ± 1.2) underwent 4,051 sessions of MWA with a median follow-up of 61.3 (0.6-169.5 range) months during 3 periods (2007-2010, 2011-2014, and 2015-2018). Technical success was achieved in 5,194 (97.5%) tumors with significant improvement over time, especially for >3.0-cm HCC (p < 0.001). Local tumor progression (LTP) showed no period-dependent advance, with >3.0-cm HCC and perivascular location being the risk factors for LTP. The median intrahepatic metastasis time was 27.6 (95% confidence interval [CI]: 25.2-28.8) months, with 5- and 10-year occurrence rates of 68.8% and 79.4%, respectively. The 5- and 10-year overall survivals were 63.9% and 41.1%, respectively, and BCLC stage 0, A, and all B patients showed an observable survival improvement over time (p < 0.001). The median disease-free survival time increased from 19.4 (95% CI: 16.5-22.6) months in 2007-2010 to 28.1 (95% CI: 25.9-32.3) months in 2015-2018. The improved survival for early recurrent (≤2 years) patients was period-dependent, as verified by Cox regression analyses. The major complications rate per procedure was 3.0% (122/4,051). Conclusions: These real-world data show that MWA provided an upward trend in survival for HCC patients with BCLC stage 0-B over a 12-year follow-up period. An encouraging clear survival benefit in early recurrent patients was also observed.

US Shear-Wave Elastography Dispersion for Characterization of Chronic Liver Disease.

Background Little is known about the benefits of the use of dispersion slope (DS) as a viscosity-related parameter derived from two-dimensional (2D) shear-wave elastography (SWE) in the stratification of hepatic pathologic stages. Purpose To evaluate whether DS as an additional parameter can improve the diagnostic performance in detecting liver necroinflammation, fibrosis, and steatosis. Materials and Methods In this prospective study, consecutive participants with chronic liver disease who underwent liver biopsy and 2D SWE were recruited between July 2019 and September 2020. DS and liver stiffness (LS) measurements were obtained with use of a 2D SWE system immediately before biopsy. The biopsy specimens were assessed to obtain the scores of fibrosis, necroinflammation, and steatosis. Differences in the area under the receiver operating characteristic curve (AUC) were used to compare the diagnostic performance of DS, LS, and a combination of DS and LS. Results There were 159 participants evaluated (among them, 79 participants with chronic hepatitis B and 11 participants with nonalcoholic fatty liver disease). The distributions of DS values among various necroinflammatory activities (P = .02) and fibrosis stages (P < .001) were different. Moreover, DS was only associated with fibrosis after subgroup analysis based on the fibrosis stages and necroinflammatory activities (P < .001). The AUCs of DS in detecting clinically significant fibrosis (fibrosis stage ≥F2), cirrhosis (fibrosis stage of F4), and moderate to severe necroinflammatory activity (necroinflammatory activity ≥A2) were 0.72 (95% CI: 0.64, 0.79), 0.71 (95% CI: 0.63, 0.78), and 0.64 (95% CI: 0.55, 0.71), respectively. The differences of AUCs were not apparent for the DS and LS combination model after excluding DS (fibrosis stage ≥F2: 0.00 [95% CI: 0.00, 0.01], fibrosis stage of F4: -0.01 [95% CI: -0.02, 0.00], and necroinflammatory activity ≥A2: 0.00 [95% CI: 0.00, 0.01]). Conclusion The addition of dispersion slope derived from two-dimensional shear-wave elastography did not improve the diagnostic performance in detecting liver fibrosis, necroinflammation, or steatosis in patients with primarily viral hepatitis. ClinicalTrials.gov registration no.: NCT03777293 © RSNA, 2022 Online supplemental material is available for this article.

Polymerase chain reaction-based assays facilitate the breeding and study of mouse models of Klinefelter syndrome.

Klinefelter syndrome (KS) is one of the most frequent genetic abnormalities and the leading genetic cause of nonobstructive azoospermia. The breeding and study of KS mouse models are essential to advancing our knowledge of the underlying pathological mechanism. Karyotyping and fluorescence in situ hybridization are reliable methods for identifying chromosomal contents. However, technical issues associated with these methods can decrease the efficiency of breeding KS mouse models and limit studies that require rapid identification of target mice. To overcome these limitations, we developed three polymerase chain reaction-based assays to measure specific genetic information, including presence or absence of the sex determining region of chromosome Y (Sry), copy number of amelogenin, X-linked (Amelx), and inactive X specific transcripts (Xist) levels. Through a combined analysis of the assay results, we can infer the karyotype of target mice. We confirmed the utility of our assays with the successful generation of KS mouse models. Our assays are rapid, inexpensive, high capacity, easy to perform, and only require small sample amounts. Therefore, they facilitate the breeding and study of KS mouse models and help advance our knowledge of the pathological mechanism underlying KS.

Usefulness of New Shear Wave Elastography Technique for Noninvasive Assessment of Liver Fibrosis in Patients with Chronic Hepatitis B: A Prospective Multicenter Study.

PURPOSE: To explore the usefulness of liver stiffness measurements (LSMs) by sound touch elastography (STE) and sound touch quantification (STQ) in chronic hepatitis B (CHB) patients for staging fibrosis. METHODS: This prospective multicenter study recruited normal volunteers and CHB patients between May 2018 and October 2019. The volunteers underwent LSM by STE and supersonic shear imaging (SSI) or by STQ and acoustic radiation force impulse imaging (ARFI). CHB patients underwent liver biopsy and LSM by both STE/STQ. The areas under the receiver operating characteristic curves (AUCs) for staging fibrosis were calculated. RESULTS: Overall, 97 volunteers and 524 CHB patients were finally eligible for the study. The successful STE and STQ measurement rates were both 100 % in volunteers and 99.4 % in CHB patients. The intraclass correlation coefficients (ICCs) for the intra-observer stability of STE and STQ (0.94; 0.90) were similar to those of SSI and ARFI (0.95; 0.87), respectively. STE and STQ showed better accuracy than the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) (AUC: 0.87 vs 0.86 vs 0.73 vs 0.77) in staging cirrhosis. However, both STE and STQ were not superior to APRI and FIB-4 in staging significant fibrosis (AUC: 0.76 vs 0.73 vs 0.70 vs 0.71, all P-values > 0.05). CONCLUSION: STE and STQ are convenient techniques with a reliable LSM value. They have a similar diagnostic performance and are superior to serum biomarkers in staging cirrhosis in CHB patients.

Shear-Wave Dispersion Slope of the Liver: Effect of Study Protocol and Ascites on the Measurement Applicability.

This study aimed to evaluate the shear-wave dispersion (SWD) scanning protocol including the minimum number of measurements and better size of the region of interest (ROI), as well as the influence of ascites on the measurement applicability. Patients who had undergone serial SWD examinations between July 2019 and December 2020 were included. In patients with chronic liver disease (group A), two different ROI sizes were applied, and at least 10 measurements were repeated to determine the minimum number of measurements and better ROI size. In patients with liver failure (group B), failure and unreliable results were compared between patients with and without ascites. A minimum of five measurements when using a 20-mm ROI and six measurements when using a 10-mm ROI were required. Compared with using a 20-mm ROI, a 10-mm ROI showed a higher unreliable rate. The failure and unreliable rates of SWD in patients with ascites were significantly higher than those in patients without ascites. SWD examination required at least five measurements when using a 20-mm ROI and six measurements when using a 10-mm ROI. A larger ROI was associated with higher reliability, and ascites influenced the failure and reliability of the SWD measurement.

Polymerase chain reaction-based assays facilitate the breeding and study of mouse models of Klinefelter syndrome / 亚洲男科学杂志(英文版)

Klinefelter syndrome (KS) is one of the most frequent genetic abnormalities and the leading genetic cause of nonobstructive azoospermia. The breeding and study of KS mouse models are essential to advancing our knowledge of the underlying pathological mechanism. Karyotyping and fluorescence in situ hybridization are reliable methods for identifying chromosomal contents. However, technical issues associated with these methods can decrease the efficiency of breeding KS mouse models and limit studies that require rapid identification of target mice. To overcome these limitations, we developed three polymerase chain reaction-based assays to measure specific genetic information, including presence or absence of the sex determining region of chromosome Y (Sry), copy number of amelogenin, X-linked (Amelx), and inactive X specific transcripts (Xist) levels. Through a combined analysis of the assay results, we can infer the karyotype of target mice. We confirmed the utility of our assays with the successful generation of KS mouse models. Our assays are rapid, inexpensive, high capacity, easy to perform, and only require small sample amounts. Therefore, they facilitate the breeding and study of KS mouse models and help advance our knowledge of the pathological mechanism underlying KS.

Effect of ferroptosis inducer Erastin on apoptosis of colorectal cancer induced by Shikonin / 中国药理学通报

Aim To explore the effect of ferroptosis inducer Erastin combined with Shikonin on the anti-tumor activity of colorectal cancer cells and its mechanism.Methods Erastin(0,4,8,16,32,64 μmol·L-1)and Shikonin(SW-480:0, 0.5,1,2,4,8 μmol·L-1 with SW-620:(0,0.2,0.4,0.8,1.6,3.2 μmol·L-1)alone and 10 μmol·L-1 Erastin combined with various concentrations of Shikonin were used to treat colorectal cancer cells SW480 and SW620; Cell viability was detected by CCK-8 method and the apoptosis was detected by AnnexinV/PI double staining.The changes of active oxygen content in colorectal cancer cells were measured by ROS detection kit, and the changes of intracellular lactic acid content in SW480 and SW620 were measured by 10 μmol·L-1 Erastin alone or in combination with 2 μmol·L-1 and 1 μmol·L-1 Shikonin, respectively.The protein expressions of Bax, Bcl-2, PARP1, Caspase3,Caspase8,AKT and P-akt in SW480 and SW620 cells were detected by Western blot.Results The results of CCK-8 showed that the combination group could significantly inhibit the viability of colorectal cancer cells and the apoptotic rate was the highest.At the same time, lactic acid was inhibited most obviously.The content of intracellular reactive oxygen species and apoptosis-related proteins also changed significantly.Conclusions Erastin combined with Shikonin can synergistically induce the apoptosis of colorectal cancer cells.The mechanism may be inhibiting the production of lactic acid in tumor cells, increasing the content of reactive oxygen species in tumor cells, inhibiting the AKT signaling pathway, and activating pro-apoptotic proteins to induce colorectal cancer cell apoptosis.

An Optimal Ablative Margin of Small Single Hepatocellular Carcinoma Treated with Image-Guided Percutaneous Thermal Ablation and Local Recurrence Prediction Base on the Ablative Margin: A Multicenter Study.

OBJECTIVE: To explore the best ablative margin (AM) for single hepatocellular carcinoma (HCC) patients with image-guided percutaneous thermal ablation (IPTA) based on MRI-MRI fusion imaging, and to develop and validate a local tumor progression (LTP) predictive model based on the recommended AM. METHODS: Between March 2014 and August 2019, 444 treatment-naïve patients with single HCC (diameter ≤3 cm) who underwent IPTA as first-line treatment from three hospitals were included, which were randomly divided into training (n= 296) and validation (n = 148) cohorts. We measured the ablative margin (AM) by MRI-MRI fusion imaging based on pre-ablation and post-ablation images. Then, we followed up their LPT and verified the optimal AM. Risk factors related to LTP were explored through Cox regression models, the nomogram was developed to predict the LTP risk base on the risk factors, and subsequently validated. The predictive performance and discrimination were assessed and compared with conventional indices. RESULTS: The median follow-up was 19.9 months (95% CI 18.0-21.8) for the entire cohort. The results revealed that the tumor size (HR: 2.16; 95% CI 1.25-3.72; P = 0.003) and AM (HR: 0.72; 95% CI, 0.61-0.85; P < 0.001) were independent prognostic factors for LTP. The AM had a pronounced nonlinear impact on LTP, and a cut-off value of 5-mm was optimal. We developed and validated an LTP predictive model based on the linear tumor size and nonlinear AM. The model showed good predictive accuracy and discrimination (training set, concordance index [C-index] of 0.751; validation set, C-index of 0.756) and outperformed other conventional indices. CONCLUSION: The 5-mm AM is recommended for the best IPTA candidates with single HCC (diameter ≤3 cm). We provided an LTP predictive model that exhibited adequate performance for individualized prediction and risk stratification.

CEUS detection of biliary ischaemia during the first 4 weeks after liver transplantation predicts non-anastomotic biliary stricture.

BACKGROUND: Biliary ischaemia is an important factor in the pathogenesis of non-anastomotic biliary stricture (NAS) after liver transplantation (LT). Contrast-enhanced ultrasound (CEUS) can be used to detect biliary ischaemia, but no study has examined the utility of CEUS in predicting NAS. OBJECTIVE: To evaluate whether repeated CEUS as a non-invasive method of biliary ischaemia can identify NAS. METHODS: Consecutive LT patients who underwent CEUS examinations at 1-4 weeks after LT from September 2012 to December 2015 at our institution were included. The CEUS images and clinical data were analysed. RESULTS: Among 116 eligible LT patients, 39 (33.6%) were diagnosed with NAS within 1 year after LT. The patients with NAS had a significantly higher CEUS score at weeks 2-4 (all P < 0.05) and a higher slope of CEUS score progression (0.480 vs -0.044, P < 0.001). The accuracy of CEUS in identifying NAS improved over time after LT, reaching its maximum at week 4, with a sensitivity of 66.7%, a specificity of 87.9%, a positive predictive value (PPV) of 75.9%, a negative predictive value (NPV) of 82.3%, and an accuracy of 80.2%in the full cohort when a CEUS score≥3 was used as the cut-off. Multivariate analysis identified gamma-glutamyl transpeptidase (GGT), alanine transaminase (ALT) and the CEUS score at week 4 as independent predictors of NAS. In the task of identifying NAS, an NAS score combining the above 3 variables at week 4 showed areas under the receiver operating characteristic curve of 0.88 (95%CI, 0.78-0.99) in the estimation group (n = 60) and 0.82 (95%CI, 0.69-0.96) in the validation group (n = 56). An NAS score cut-off of 0.396 identified 87.2%of NAS cases in the estimation group, with a PPV of 93.3%; and 75.0%of NAS cases in the validation group, with a PPV of 58.8%. CONCLUSIONS: CEUS examination during the first 4 weeks is useful in assessing the risk of NAS within 1 year after LT. In particular, an NAS score combining the CEUS score, GGT level, and ALT level at week 4 can be used to accurately predict the risk of NAS in LT patients.

Role of ultrasound in the diagnosis of primary and recurrent dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare, low- to intermediate-grade sarcoma, which represents a diagnostic imaging challenge. This study aimed to analyze the clinical and ultrasound features of primary and recurrent DFSP to improve the diagnosis. METHODS: Clinical, imaging, and pathological data from a total of 58 patients (23 patients with primary DFSP and 35 patients with recurrent DFSP) were retrospectively reviewed. RESULTS: There was no statistically significant difference in age, sex, tumor size, or echogenicity between the two groups. Most of the primary DFSP lesions involved the overlying dermis and hypodermis, while most of the recurrent DFSP lesions were fixated to more deeply seated structures at the original surgical incision. Red nodules on the skin were found more frequently in the primary group. There were statistically significant differences in the type of lesion and ultrasound tumor morphology (p < 0.050). The lesions in the primary group showed more tentacle-like projections or a "claw" sign, while the lesions in the recurrent group were more commonly oval, lobulated, and irregularly shaped. Hypervascularity was common in both groups. CONCLUSIONS: For primary DFSP, a slow-growing, red nodule on the skin involving the overlying dermis and hypodermis, more frequently a hypoechoic mass with tentacle-like projections or a "claw" sign, was observed. For recurrent DFSP, palpable subcutaneous nodules or subcutaneous masses at the original surgical incision and oval, lobulated, and irregularly shaped lesions were more commonly observed. This may be useful for improving diagnostic accuracy.