Sirtuin 6 Deacetylates Apoptosis-Associated Speck-Like Protein (ASC) to Inhibit Endothelial Cell Pyroptosis in Atherosclerosis.

Endothelial cell dysfunction is the main pathology of atherosclerosis (AS). Sirtuin 6 (SIRT6), a deacetylase, is involved in AS progression. This study aimed to investigate the impacts of SIRT6 on the pyroptosis of endothelial cells and its underlying mechanisms. ApoE-/- mice were fed a high-fat diet (HFD) to establish the AS mouse model, atherosclerotic lesions were evaluated using oil red O staining, and blood lipids and inflammatory factors were measured using corresponding kits. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish the cell model, and pyroptosis was evaluated by flow cytometry, ELISA, and western blot. Immunoprecipitation (IP), co-IP, western blot, and immunofluorescence were used to detect the molecular mechanisms. The results showed that SIRT6 expression was downregulated in the blood of HFD-induced mice and ox-LDL-induced HUVECs. Overexpression of SIRT6 reduced atherosclerotic lesions, blood lipids, and inflammation in vivo and suppressed pyroptosis of HUVECs in vitro. Moreover, SIRT6 interacted with ASC to inhibit the acetylation of ASC, thus, reducing the interaction between ASC and NLRP3. Moreover, SIRT6 inhibits endothelial cell pyroptosis in the aortic roots of mice by deacetylating ASC. In conclusion, SIRT6 deacetylated ASC to inhibit its interaction with NLRP3 and then suppressed pyroptosis of endothelial cells, thus, decelerating the progression of AS. The findings provide new insights into the function of SIRT6 in AS.

Diagnostic performance and clinical impacts of metagenomic sequencing after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Metagenomic Next-Generation Sequencing (mNGS) is a rapid, non-culture-based, high-throughput technique for pathogen diagnosis. Despite its numerous advantages, only a few studies have investigated its use in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective analysis of 404 mNGS tests performed on 264 patients after allo-HSCT. The tests were divided into three groups (Phase A, B, C) based on the time spent hospitalized post-transplantation, and we evaluated the analytical performance of mNGS in comparison with conventional microbiological tests (CMT), while also analyzing its clinical utility for clinical impacts. RESULTS: Metagenomic sequencing demonstrated a significantly higher rate of positive microbiological findings as compared to CMT (334/404 (82.7 %) vs. 159/404 (39.4 %), respectively, P < 0.001). The detection rates by both mNGS and CMT varied across the three-phase (mNGS: A-60/89 (67.4 %), B-147/158 (93.0 %), C-125/157 (79.6 %), respectively, P < 0.001; CMT: A-21/89 (23.6 %), B-79/158 (50.0 %), C-59/157 (37.6 %), respectively, P < 0.001). The infection sites and types of pathogens were also different across the three phases. Compared to non-GVHD cases, mNGS detected more Aspergillus spp. and Mucorales in GVHD patients (Aspergillus: 12/102 (11.8 %) vs. 8/158 (5.1 %), respectively, P = 0.048; Mucorales: 6/102 (5.9 %) vs. 2/158 (1.3 %), respectively, P = 0.035). Forty-five (181/404) percent of mNGS tests yielded a positive impact on the clinical diagnosis, while 24.3 % (98/404) of tests benefited the patients in antimicrobial treatment. CONCLUSION: mNGS is an indispensable diagnostic tool in identifying pathogens and optimizing antibiotic therapy for hematological patients receiving allo-HSCT.

Management strategies for acute cholecystitis in late pregnancy: a multicenter retrospective study.

OBJECTIVE: This study aims to investigate the management strategies for acute cholecystitis in the third trimester of pregnancy by comparing the effectiveness of three different treatments. METHODS: Clinical data of 102 patients with acute cholecystitis in third trimester of pregnancy admitted to three Tertiary Hospitals from January 2010 to June 2020 were collected and divided into 3 groups according to the primary treatment during their first hospitalization: Group A (surgical group; n = 11), Group B (percutaneous transhepatic gallbladder drainage (PTGD) group, n = 29) and Group C (conservative treatment group, n = 62). The length of stay, readmission rate, and preterm delivery rate of each group were analyzed retrospectively. RESULTS: The average age of patients included in this study was 29 ± 2.16 years with an average gestational cycle of 35.26 ± 1.02 weeks. The readmission rates of patients in groups A, B, and C were 9.09%, 24.14%, and 58.06%; the preterm delivery rates were 9.09%, 3.45%, and 12.90%; and the length of stay was 4.02 ± 1.02 days, 12.53 ± 2.21 days, and 11.22 ± 2.09 days, respectively. The readmission rate was lower in group A than in groups B and C, the preterm delivery rate was lower in group B than in groups A and C, and the length of stay was shorter in group A than in groups B and C (all with statistically significant differences, P < 0.05). CONCLUSION: Patients with acute cholecystitis in late pregnancy need to be appropriately graded for severity and offered a sound treatment strategy after a thorough assessment of the condition while taking into account the willingness of the patients. For patients with mild severity, conservative treatment can be adopted; for patients with moderate or severe inflammation, PTGD can be performed first for symptom control, and wait till after delivery for surgery to be considered; and in some cases of critical condition and poor symptom control, surgical intervention should be promptly performed.

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome: a case report.

A biopsy of gastrocnemius muscle from a patient with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome was studied histologically in semithin sections stained by hematoxylin-and-eosin (H&E) and toluidine blue, and ultrathin sections by transmission electron microscopy (TEM). H&E stain demonstrated typical ragged-red fibers (RRFs) and affected fibers in fascicles. Toluidine-blue stain showed an irregular meshwork in the center of RRFs. TEM demonstrated damaged myofibrils and variations in mitochondrial structure in RRFs and affected fibers. Dense mitochondria were compacted with cristae and pleomorphic electron-dense inclusions. Lucent mitochondria included paracrystalline inclusions with a parking lot appearance. At high magnification, the paracrystalline inclusions were composed of plates that paralleled and connected with mitochondrial cristae. These observations indicated that electron-dense granular and paracrystalline inclusions resulted from cristal degeneration and overlapping in mitochondria in MELAS syndrome.

Utility of plasma cell-free DNA next-generation sequencing for diagnosis of infectious diseases in patients with hematological disorders.

BACKGROUND: Plasma cell-free DNA Next-Generation Sequencing has been used as a non-invasive and comprehensive method for the etiological diagnosis of infectious diseases. However, only a handful of studies have described the real-world utility of this technique in patients with hematological disorders, a cohort of patients that are distinctive due to neutropenia and weakened immune functions. METHODS: We retrospectively analyzed the results of plasma cell-free DNA sequencing performed on 184 and 163 specimens collected from hematological patients suspected of infections with (Group I) or without (Group II) neutropenia, respectively. The diagnostic performance and the clinical impact of plasma sequencing were comparatively evaluated to conventional microbiological tests and a composite reference standard (conventional tests combined with the clinical assessment). RESULTS: The overall positive detection rate of plasma cell-free DNA sequencing was significantly higher than that of conventional microbiological tests (72.6% vs.31.4%, P < 0.001). The positive rate of conventional microbiological tests in Group I was lower than that in Group II (25.5% vs. 38.0%, P = 0.012). Combining plasma sequencing with conventional tests yielded a positive detection rate of 75.0% and 74.8% for these two groups, respectively. Using the composite reference standard, the sensitivity and specificity of plasma sequencing were 89.1% and 65.1%, respectively. The proportions of the positive impact of cell-free DNA sequencing results in the Group I were higher than in the Group II in terms of both diagnosis and treatment (diagnosis: 54.3% vs. 40.5%, P = 0.013; treatment: 45.7% vs.30.7%, P = 0.004). A total of 73 patients (21.0%) benefited from plasma sequencing through adjustment of the antibiotic regimen. CONCLUSIONS: The diagnostic yield of conventional microbiological tests was low in patients with neutropenia. Combining conventional tests with plasma cell-free DNA sequencing significantly improved the detection rate for pathogens and optimized antibiotic treatment. Our findings on the clinical impact warrant confirmation through larger, multicenter, randomized controlled trials. Moreover, the cost-effectiveness of this testing strategy remains unknown and requires further exploration.

Feasibility of contrast-enhanced ultrasonography (CEUS) in evaluating renal microvascular perfusion in pediatric patients.

BACKGROUND: Changes in renal microvascular perfusion are involved in several kidney diseases. Contrast-enhanced ultrasonography (CEUS) quantitative analysis can enable the estimation of renal microvascular perfusion non-invasively. However, to date, few pediatric patients with renal disease have been subjected to CEUS quantitative analysis. This study aimed to explore the feasibility of CEUS in evaluating renal microvascular perfusion in pediatric patients and paving its way to clinical practice. METHODS: Seventeen pediatric patients with chronic kidney disease (CKD) and five children without kidney disease were consecutively examined using CEUS. Quantitative analysis of CEUS images based on time-intensity curve (TIC) fittings was performed using specialized software. Quantitative parameters of wash-in microvascular blood flow, including A, k, B, and TtoPk, were generated from three regions of interest (ROIs) each in the cortex and medulla of each kidney. RESULTS: CEUS was performed in all children successfully and safely without the use of sedatives. All parameters (A, B, k, and TtoPk) demonstrated no statistical differences among the three sampling ROIs in the renal cortex and medulla. All parameters (A, B, k, and TtoPk) showed no statistical differences between the left and right sides of kidneys both in cortices and medullas. Comparing with patients with CKD stage 3-5, both control group and patients with CKD stage 1-2 had significantly higher values of parameter A in the renal cortex (p = 0.025 and p = 0.031, respectively). In control group and patients stage 1-2, the values of parameters k in the renal cortices were significantly higher than that in the renal medullas, while in patients with CKD stage 3-5, parameter k showed no statistically significant differences between the renal cortex and medulla (p = 0.173). CONCLUSION: CEUS is safe and practicable in pediatric patients with chronic kidney disease. Renal microvascular perfusion estimated by CEUS could be a robust approach in the evaluation of pediatric renal diseases. Parameters A and k derived from CEUS quantitative analysis can provide great potential in non-invasive assessment of renal microvascular perfusion impairment in pediatric CKD.

The novel SLC40A1 (T419I) variant results in a loss-of-function phenotype and may provide insights into the mechanism of large granular lymphocytic leukemia and pure red cell aplasia.

Variants in the solute carrier family 40 member 1 (SLC40A1) gene are the molecular basis of ferroportin disease, which is an autosomal dominant hereditary hemochromatosis. Here, we present a patient with pure red cell aplasia (PRCA) and large granular lymphocytic leukemia (LGLL) associated with an extremely high levels of serum ferritin and iron overload syndrome. Whole exon sequencing revealed a novel heterozygous variant in SLC40A1 (p.T419I), which was found in his daughter as well. A series of functional studies in vitro of the T419I variant in ferroportin were conducted and the results revealed a reduced capacity of iron export from cells without changes in protein localization and its sensitivity to hepcidin. Intracellular iron storage in mutated cells was significantly higher than that of wild-type. These findings suggest that the novel variant p.T419I can cause the classical form of ferroportin disease and an elevated intracellular iron level indicates a potential novel pathogenic mechanism underlying PRCA and LGLL.

A Review of Clinical Applications for Super-resolution Ultrasound Localization Microscopy.

Microvascular structure and hemodynamics are important indicators for the diagnosis and assessment of many diseases and pathologies. The structural and functional imaging of tissue microvasculature in vivo is a clinically significant objective for the development of many imaging modalities. Contrast-enhanced ultrasound (CEUS) is a popular clinical tool for characterizing tissue microvasculature, due to the moderate cost, wide accessibility, and absence of ionizing radiation of ultrasound. However, in practice, it remains challenging to demonstrate microvasculature using CEUS, due to the resolution limit of conventional ultrasound imaging. In addition, the quantification of tissue perfusion by CEUS remains hindered by high operator-dependency and poor reproducibility. Inspired by super-resolution optical microscopy, super-resolution ultrasound localization microscopy (ULM) was recently developed. ULM uses the same ultrasound contrast agent (i.e. microbubbles) in CEUS. However, different from CEUS, ULM uses the location of the microbubbles to construct images, instead of using the backscattering intensity of microbubbles. Hence, ULM overcomes the classic compromise between imaging resolution and penetration, allowing for the visualization of capillary-scale microvasculature deep within tissues. To date, many in vivo ULM results have been reported, including both animal (kidney, brain, spinal cord, xenografted tumor, and ear) and human studies (prostate, tibialis anterior muscle, and breast cancer tumors). Furthermore, a variety of useful biomarkers have been derived from using ULM for different preclinical and clinical applications. Due to the high spatial resolution and accurate blood flow speed estimation (approximately 1 mm/s to several cm/s), ULM presents as an enticing alternative to CEUS for characterizing tissue microvasculature in vivo. This review summarizes the principles and present applications of CEUS and ULM, and discusses areas where ULM can potentially provide a better alternative to CEUS in clinical practice and areas where ULM may not be a better alternative. The objective of the study is to provide clinicians with an up-to-date review of ULM technology, and a practical guide for implementing ULM in clinical research and practice.

Relationship between Vesicoureteral Reflux and Glomerular Filtration Rate in Children.

Vesicoureteral reflux (VUR) is one of the most common urinary tract anomalies in children and causes renal damage and studies focusing on the effect of VUR on renal function are rare. We recruited 35 primary VUR patients with recurrent urinary tract infection (UTI) and 10 non-VUR patients with recurrent UTI. Contrast-enhanced voiding urosonography (ceVUS) was performed for VUR grading, and renal dynamic imaging was used for evaluating glomerular filtration rate (GFR, mL/min). Standardized GFR (sGFR), namely GFR/BSA (mL·min-1·m-2), was calculated based on the body surface area (BSA). Total sGFR (tsGFR, mL·min-1·m-2) was obtained from the sum of sGFR on the left and right sides of all the children. The risk of renal regurgitation was equal in the unilateral reflux group. The sGFR of children with grade IV (45.74±18.05 mL·min-1·m-2) and grade V (49.67±23.63 mL·min-1·m-2) reflux was significantly lower than that in children with grade III (77.69 ±22.21 mL·min-1·m-2). The renal function compensation of contralateral non-reflux kidney increased in unilateral reflux group, which was higher than that in the control group and level II, IV and V of reflux group respectively. In VUR group of the same grade, sGFR decreased with the age at diagnosis. In unilateral grade V reflux group, the tsGFR was lower than that in the unilateral grade III reflux group (133.51±48.21 vs. 186.87±53.49 mL·min-1·m-2). The patients with VUR of unilateral grade II were significantly older than those with VUR of unilateral grades III and IV. This study indicates that severe VUR is significantly associated with decreased renal function. Therefore, VUR should be diagnosed early and managed individually.

Early Identification of Residual Tumors following Microwave Ablation Using Contrast-Enhanced Ultrasonography in a Rabbit VX2 Liver Cancer Model.

OBJECTIVE: It is difficult to evaluate the ablation effect immediately after thermal ablation of liver cancer by clinical imaging methods, due to the immediate formation of an annular inflammatory reaction band (IRB). This study is aimed at exploring the early identification indicators of the IRB and residual tumor postmicrowave ablation (MVA) using contrast-enhanced ultrasonography (CEUS). METHODS: MVA was used to inactivate part of the tumor nodules in rabbit VX2 liver cancer models, leading to the coexistence of the IRB with residual tumors. Quantitative analysis of the perfusion parameters of the tumor and ablation zone was performed using CEUS, followed by liver biopsy and VEGFR-2 immunohistochemical staining. RESULTS: All rabbits successfully tolerated VX2 tumor inoculation and MVA operation. No statistically significant difference existed between the IRB vs. residual tumors, the IRB vs. junctional areas, and residual tumors postablation vs. VX2 tumors before ablation in regional blood volume, blood velocity, and blood flow estimated by parameters A, k, and A ∗ k of CEUS quantitative analysis. There was a statistically significant difference between the IRB and normal liver parenchyma in regional blood velocity and blood flow (p = 0.005 and p = 0.023, respectively). Normal liver parenchyma showed nonspecific VEGFR-2 staining, while VX2 tumor before ablation and residual tumor after ablation both showed positive VEGFR-2 staining; the necrosis zone showed negative staining by VEGFR-2 immunohistochemical staining. CONCLUSION: MVA had no significant effect on the residual tumor hemodynamics. The blood flow in the IRB increased significantly as compared to normal liver parenchyma, resembling tumor hemodynamic patterns. CEUS can detect residual tumors immediately postablation only when they protrude from the annular-shaped IRB. In addition, VEGFR-2 targeted CEUS may have a great potential for detecting residual tumor after thermal ablation of hepatocellular carcinoma.

A quantitative grading system of vesicoureteral reflux by contrastenhanced voiding urosonography.

AIMS: Contrast-enhanced voiding urosonography (ceVUS) is a well-established imaging modality for the diagnosis of vesicoureteral reflux (VUR). However, discrepancies of grading diagnosis of VUR exist due to the qualitative grading criteria currently used in clinics. This study aimed to evaluate numerical markers for a quantitative VUR grading system. MATERIAL AND METHODS: CeVUS images of grade II-VVUR were analysed. A quantitative indicator, i.e. sectional area ratio (SAR), on the imaging section with maximum cross-section area and the presence of kidney hilum was calculated to distinguish different grades of VUR. The diagnostic performance of SAR was evaluated using receiver operating characteristic curve (ROC) analysis, and the maximum Youden Index was used to determine the optimal cut-off values. RESULTS: A total of 63 patients with 126 PelviUreteral Units were enrolled. The SAR value increased significantly along with the increase of VUR grade. SAR had an excellent diagnostic performance in grading VUR. For differentiating VUR of grade II vs III, III vs IV and IV vs V, the area under the ROC curve values of SAR were 0.967, 0.943 and 0.865, respectively, while the optimal SAR cut-off values were 14.3%, 34.9% and 51.0%, respectively. The quantitative grading system based on the optimal SAR cut-off values showed excellent consistency with the qualitative grading system of VUR currently used in clinic. CONCLUSIONS: The numerical indicator SAR calculated from ceVUS may be used to establish a quantitative VUR grading system with excellent diagnostic performance and can potentially serve as a reliable tool for the evaluation and follow-up of VUR.

Reference intervals of mesenteric lymph node size according to lymphocyte counts in asymptomatic children.

There is no acknowledged reference interval of mesenteric lymph node size in healthy children, and the size criterion for mesenteric lymph node enlargement (MLNE) has long been controversial. This study aimed to explore the reference intervals of mesenteric lymph node size according to lymphocyte counts in asymptomatic children and to develop a more appropriate definition of MLNE. The asymptomatic children included were divided into five age strata: 2 to 3 yr; 3 to 4 yr; 4 to 5 yr; 5 to 6 yr; and 6 to 7 yr. Correlation analyses between lymphocyte counts and the long-axis diameter, short-axis diameter, and average diameter of the largest mesenteric lymph node (LMLN) were performed. A reference interval of the short-axis diameter of LMLN was established according to this correlation analysis in each age group. We also report a reference interval of lymphocyte count in each age group. This study revealed significant correlations between the short-axis diameter of LMLN and lymphocyte count in all age groups, as well as in subdivided boy groups and girl groups. The overall reference interval of the short-axis diameter of LMLN in children was 0.54 cm-1.03 cm, with mean value of 0.75 cm. This study supports the use of the short-axis diameter greater than 8-10 mm as the diagnostic criterion for primary mesenteric lymphadenitis based on the presence of a cluster of three or more mesenteric lymph nodes and in the absence of other abnormalities.

Establishment of Rabbit Liver VX2 Tumor Model Using Percutaneous Puncture Inoculation of Tumor Fragment Guided and Evaluated by Ultrasonography.

The aim of the present study is to evaluate a method of establishing model of rabbit liver VX2 tumor using percutaneous puncture inoculation of tumor fragment guided by ultrasonography. VX2 tumor fragments were implanted into the liver of 13 New Zealand white rabbits flushed by 1 mL normal saline through percutaneous puncture needle guided by ultrasonography. Conventional ultrasonography and contrast-enhanced ultrasonography (CEUS) were performed 14 days after inoculation, and then the rabbits were sacrificed and pathologically examined. The success rate of inoculation was 100%. The average size of liver VX2 tumor was 1.7 cm×1.3 cm, CEUS of VX2 liver tumors showed the "rapid wash-in and wash-out" vascular pattern. There were significant differences between VX2 tumors and liver parenchyma in quantitative parameters of A, k and A × k (P<0.05), which meant that VX2 liver tumors were characterized by more blood flow volume and faster blood velocity than liver parenchyma. Tumor fragment flushed by normal saline into the liver through a needle may be a promising method for the induction of a hepatic tumor. And CEUS can be used for accurately assessing angiogenesis and blood perfusion of VX2 tumors.

Value of contrast-enhanced ultrasound for preoperative assessment of liver reserve function in patients with liver tumors.

This study aimed to investigate the value of contrast-enhanced ultrasound (CEUS) for preoperative assessment of liver reserve function in patients with liver tumors. The indocyanine green (ICG) clearance tests and CEUS examinations of 45 noncirrhotic patients with liver tumors were performed prior to liver resection. Parameters time to peak (TtoPk), arrival time (Atm) as well as perfusion parameters A, k and A x k were generated from time-intensity curve (TIC) of CEUS. The correlation analyses of the ICG clearance per unit time (ICGK) and the retention rate at 15 min (ICGR15) with TtoPk, Atm, A, k and A x k were performed, and the diagnostic ability as well as optimal cut-off values of TtoPk and Atm for differentiating patients with ICGR15>10% from ICGR15<10% were analyzed. There were significant correlations of ICGK with TtoPk and Atm, and the correlation coefficients were 0.363 (p = 0.014) and -0.482 (p = 0.001), respectively. Significant correlations of ICGR15 with TtoPk and Atm were revealed, and the correlation coefficients were -0.416 (p = 0.004) and 0.303 (p = 0.043), respectively. No correlation of ICGK or ICGR15 with A, k and A x k was found in this study. There were significant differences in TtoPk and Atm between patients with ICGR15>10% and ICGR15<10% (p = 0.028 and p = 0.026, respectively). TtoPk and Atm both had good diagnostic abilities in diagnosing patients with ICGR15>10% verusus ICGR15<10% (AUROC = 0.711 and 0.721, respectively). For ICGR15>10% vs ICGR15, the optimal cut-off values of TtoPk and Atm were 13.307 s and 11.007 s, respectively, while the sensitivity and specificity were 75.0% and 72.7%, 60.6% and 75.0%, respectively. This study revealed that CEUS has the potential to be a new method to evaluate the liver reserve function of patients. With the optimal cut-off values of TtoPk and Atm, qualitative assessment of patients with ICGR15>10% could be more easily achieved by CEUS with good diagnostic abilities.

Contrast-enhanced voiding urosonography with intravesical administration of ultrasound contrast agent for the diagnosis of pediatric vesicoureteral reflux.

Vesicoureteral reflux (VUR) is one of the most common urinary tract anomalies in children. It has been reported that VUR may be associated with reflux nephropathy. Ultrasound contrast-enhanced voiding urosonography (CeVUS) has become a routine diagnostic method for VUR in a number of European countries; however, it is not widely used in China. The aim of the present study was to analyze the clinical application and evaluate the safety of CeVUS as a diagnostic tool for VUR in children in order to establish a standardized operating procedure for CeVUS in pediatric VUR in China. Between August 2016 and October 2017, 90 children who were susceptible to VUR were admitted into the Pediatric Nephrology Department of Tongji Hospital and underwent CeVUS. The SonoVue second-generation USA contrast agent was administered intravesically via a transurethral bladder catheter at a dose of 1 ml. The occurrence of adverse events was monitored. Urine analysis and culture were performed. A total of 90 children (47 female, 43 male; mean age, 36.6 months) with 178 Pelvi-Ureteral Units (PUUs) underwent CeVUS to screen for VUR. VUR was detected in 44/90 pediatric patients (48.89%) and 65/178 PUUs (36.52%) by CeVUS. The grade distribution of the 65 PUUs with VUS was as follows: Grade I, 3; Grade II, 9; Grade III, 14; Grade IV, 22; and Grade V, 17. The accuracy of CeVUS in the present study were consistent with previous reports. No urethral anomalies were detected and there were no adverse events. CeVUS was demonstrated to be a safe, accurate and reliable imaging technique for detecting VUR in high-risk children, including neonates. Results of the present study indicated that CeVUS can be adopted as the primary screening and follow-up method for pediatric VUR diagnoses in China.

Down-regulation of microRNA-338-3p promoted angiogenesis in hepatocellular carcinoma.

miRNAs are involved in substantial biological passways, including tumorigenesis, cancer development and progression. Angiogenesis plays a vital role in the progression of hepatocellular carcinoma (HCC), and VEGF is closely associated with the angiogenesis. However, the molecular mechanism of miRNAs in regulation tumorigenesis of HCC remains to be investigated. In the present research, we confirmed that miR-338-3p was suppressed both in HCC tissues and HCC cell lines. Then the tube formation, transwell and Chorioallantoic membrane (CAM) assay were carried out, such indicated that down-regulation of miR-338-3p can sharply increased, while up-regulation drastically suppressed angiogenesis of HCC cells in vitro. Moreover, MACC1 is predicted to be a target of miR-338-3p and we checked the prediction through luciferase assay. And then, our research showed that negative correlation existed between miR-338-3p and MACC1, ß-catenin and VEGF that has been reported participated in cancer behavior in HCC cell lines. Subsequently, our assays illustrated that suppression miR-338-3p can up-regulate MACC1, ß-catenin and VEGF expression of HCC cells. In conclusion, our research discovered that miR-338-3p can contribute to HCC angiogenesis by targeting MACC1, ß-catenin and VEGF.

Radiofrequency ablation versus surgical resection for the treatment of hepatocellular carcinoma conforming to the Milan criteria: systemic review and meta-analysis.

Radiofrequency ablation (RFA) is a promising ablation technique and has become one of the best alternatives for hepatocellular carcinoma (HCC) patients. But whether RFA or surgical resection (SR) is the better treatment for HCC conforming to the Milan criteria has long been debated. A meta-analysis of trials that compared RFA versus SR was conducted regarding the survival rate and recurrence rate. Pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using fixed or random effects models. Nineteen studies, comprising 2 randomized controlled trials and 17 non-randomized controlled trials, were included with a total of 2895 patients. The 5 years overall survival rate for SR group was significantly higher than that for RFA group. In the SR group, the local recurrence rate was significantly lower when compared with the RFA group. This meta-analysis yielded no significant differences between laparoscopic RFA and SR in 5-year overall survival rate. In conclusion, surgical resection remains the better choice of treatment for HCC conforming to the Milan criteria, whereas RFA should be considered as an effective alternative treatment when surgery is not feasible. As for RFA technique, laparoscopic approach may be more effective than percutaneous approach for HCC conforming to Milan criteria.

[The diagnosis and countermeasure for the nose-source otitis media].

OBJECTIVE: To propose the concept of rhinogenic otitis media and explore its pathomechanism through analyzing the diagnosis and treatment on secretory otitis media caused by unhealthy nasal cavity structure. METHOD: Conservative treatment and correlative operation under nasoscope were undertaken in 176 otitis media patients with unhealthy nasal cavity structure. RESULT: Of 176 cases, 156 cases recovered completely (88.64%), 18 cases got effective treatment (10.23%), and 2 cases got ineffective treatment (1.14%). CONCLUSION: One important cause of the secretory otitis media is unhealthy nasal cavity structure, so correcting the unhealthy nasal cavity structure is the main ways to treat rhinogenic otitis media.

[Application of aging donors in rat liver transplantation].

OBJECTIVE: To investigate the application of donor livers from aging rats, and discuss the age limit of the donor rats liver transplantation. METHODS: Arterialized, two-cuff technique orthotopic liver transplantation was performed in male Wistar rats. All the recipient rats were 5 months old, and the ages of the donor rats were 5 (group A), 17 (group B), 20 (group C), 23 (group D), and 26 (group E) months (n=12). The postoperative function recovery and pathological changes of the liver grafts were evaluated by serum alanine aminotransferase (ALT) detection and histopathological examination, and the 3-month survival rate of the rats was observed. RESULTS: Aging liver grafts in groups B, C, and D caused early elevation of ALT peak level and aggravation of liver tissue damage, and the liver graft recovery was delayed until postoperative day 7. Mild liver fibrosis, reduced hepatocytes and pigment deposition were observed in the liver grafts before the transplantation. Compared with the other groups, the rats in group E showed significantly increased ALT levels after the transplantation (P<0.05), with failure of liver graft function recovery and significantly reduced 3-month survival rate (0%, Plt;0.05). CONCLUSION: The donor age of the rats is a crucial factor to affect the outcome of the liver grafts. Grafts obtained from rats younger than 23 months allow better functional recovery of the liver.