Colour Doppler Sonography of the Ovarian Vein: Recognition and Associated Lesions.

AIM: The purpose of this study was to evaluate the diagnostic value of colour Doppler sonography for ovarian veins. The clinical incidence of ovarian venous lesions is relatively low and often overlooked. The ovarian veins are located deep in the pelvis, and they are relatively elongated, which could make medical imaging more difficult. Therefore, there is limited literature on the diagnosis of ovarian venous disease. The purpose of this study was to evaluate the diagnostic value of colour Doppler sonography towards ovarian vein. METHODS: A total of 37 consecutive patients with clinically suspected ovarian venous disorders were included. All the patients underwent colour Doppler sonography. CTV was performed in 31 patients, while retrograde phlebography was performed in 6 patients. CT/phlebography was the established diagnostic criterion for ovarian vein disorders. The SPSS 22.0 program was used for statistical analysis. Sensitivity, specificity, and positive and negative predictive values for colour Doppler sonography were calculated. k-test was used to evaluate consistency between colour Doppler sonography and CT/phlebography. RESULTS: In the 37 patients,18 cases were positive for ovarian vein disorders and 19 cases were negative, as assessed with colour Doppler sonography. The associated lesions included ovarian vein thrombosis (7 cases), ovarian varicocele (3 cases), and ovarian venous leiomyoma (8 cases). The calculated values of sensitivity, specificity, and positive and negative predictive value were 94.4%, 94.7%, 94.4%, and 94.7%, respectively. The overall accuracy rate was 94.9%. The k level of the degree of agreement between CT/phlebography and colour Doppler sonography was 0.892. CONCLUSION: Colour doppler sonography can provide sufficient imaging information. In clinical ultrasonography, attention should be paid to recognizing and detecting ovarian venous lesions.

Foot pain in children and adolescents: a problem-based approach in musculoskeletal ultrasonography.

Various etiologies and risk factors contribute to foot pain in children and adolescents, including conditions such as Kohler's disease, Sever's disease, Iselin's disease, rigid flat foot, accessory navicular, Freiberg's disease, sesamoiditis, os trigonum syndrome, and more. High-frequency musculoskeletal ultrasonography can show both the bone surface and the surrounding soft tissue clearly from various angles in real-time, thereby providing a higher level of detail that is helpful for identifying the etiology of foot pain and monitoring disease progression compared with other imaging modalities. This review provides an overview of the epidemiology, pathophysiology, clinical manifestations and characteristic ultrasonographic findings of select foot pain conditions in children and adolescents.

The diagnostic value of ultrasonography in evaluation of the intraneural vascular anomalies of peripheral nerves.

BACKGROUND: The imaging diagnosis of intraneural vascular anomalies of peripheral nerves mostly depended on magnetic resonance imaging (MRI), whereas high-frequency ultrasonography evaluation of intraneural vascular anomalies has been seldom done. PURPOSE: To evaluate the diagnostic value of ultrasonography in the diagnosis of intraneural vascular anomalies of peripheral nerves. MATERIAL AND METHODS: A total of 69 consecutive patients seen at Shandong Provincial Hospital Affiliated to Shandong First Medical University between February 2013 and June 2022, each with a clinical suspicion of intraneural vascular anomaly, were included. The ultrasonographic images of intraneural vascular anomalies of peripheral nerves were analyzed and the ultrasonographic features were summarized. These data were compared with MRI, which served as the gold standard for the diagnosis of intraneural vascular anomalies. The kappa statistic was adopted to determine the level of agreement. The sensitivity, specificity, positive and negative predictive values, accuracy, and Youden index of high-frequency ultrasonography as a diagnostic tool were assessed. RESULTS: Ultrasonography findings were positive in 20 of 69 patients with a clinical suspicion of intraneural vascular anomaly. The diagnosis was confirmed by MRI in 21 patients. There was one false-positive result and two false-negative results by ultrasonography. The κ value was 0.896. The sensitivity, specificity, positive and negative predictive values, accuracy, and Youden index of ultrasonography were 90.5%, 97.9%, 95%, 95.9%, 95.7%, and 0.884, respectively. CONCLUSION: Ultrasonography could be an accurate, reliable, and convenient imaging tool for the diagnosis of intraneural vascular anomalies of peripheral nerves.

Diagnostic value of high-frequency ultrasound in omohyoid muscle syndrome.

PURPOSE: To investigate the diagnostic value of high-frequency ultrasound in omohyoid muscle syndrome. MATERIAL AND METHODS: A retrospective analysis of 11 patients diagnosed with omohyoid muscle syndrome was carried out, and the characteristics of high-frequency ultrasound images were summarized. RESULTS: Ultrasonography of the omohyoid muscle showed a narrow band of hypoechoic muscle bundle. The ultrasonographic manifestation of omohyoid muscle syndrome showed a thickening of the omohyoid muscle on the affected side. The omohyoid muscle on the affected side bulged forward during swallowing and lifted the overlying sternocleidomastoid muscle. The difference between the thickness of the omohyoid muscle intermediate tendon on the affected side and the healthy side at rest was statistically significant (t = 58.23, P < 0.001). The difference between the thickness of the affected omohyoid muscle intermediate tendon at rest and during swallowing was statistically significant (t = 14.57, P < 0.001). There was no statistically significant difference between the thickness of the omohyoid muscle intermediate tendon on the healthy side at rest and during swallowing (t = 0.56, P > 0.05). CONCLUSION: High-frequency ultrasound is the preferred imaging method in the diagnosis of omohyoid muscle syndrome.

Multimodal ultrasound evaluation of asymptomatic ulnar nerve dislocation at the cubital tunnel.

Background: Ultrasonography has received broad acceptance as an effective peripheral nervous imaging examination. Shear wave elastography (SWE) can quantitatively assess the stiffness of nerves; however, little research has been conducted on elastography for ulnar nerve dislocation. The purpose of this study was thus to investigate the characteristics of multimodal ultrasound, including high-resolution ultrasonography and SWE, for asymptomatic ulnar nerve dislocation at cubital tunnel. Methods: In this prospective cross-sectional study, 41 participants were recruited in Shandong Provincial Hospital Affiliated to Shandong First Medical University in July 2022. The inclusion criteria for participants were being in good health and being 18-60 years of age. Meanwhile, the exclusion criterion was a history of upper limb pain or fractures, peripheral neuropathy, or systemic or immunological diseases. Finally, 38 participants were enrolled. Two ultrasound doctors measured the maximum diameter, the maximum cross-sectional area (CSA), and the shear modulus of the ulnar nerve at the cubital tunnel independently. Another two ultrasound doctors determined whether dislocation was present during dynamic elbow flexion and extension and divided the elbows into a dislocation group and a control group. The descriptive statistics and independent sample t-test were used for data analysis, and intragroup correlation coefficient (ICC) was used to determine the consistency of evaluation between observers. Results: Ulnar nerve dislocation was observed in 15.8% (12/76) of the ulnar nerves. There was no significant difference in the maximum diameter between the dislocation group (0.194±0.022 cm) and the control group (0.181±0.023 cm) (t=1.888; P=0.063). The CSA and SWE of the ulnar nerve were 0.064±0.009 cm2 and 43.629±6.737 kPa in the dislocation group, respectively, and were 0.050±0.008 cm2 and 31.293±7.858 kPa in the control group, respectively. There were significant differences between the two groups in terms of CSA (P<0.001) and SWE (P<0.001). The ICCs of the maximum diameter, CSA, and SWE values between observers were 0.970, 0.900, and 0.915, respectively. Conclusions: Multimodal ultrasound consisting of high-resolution ultrasonography combined with elastography can comprehensively and quantitatively evaluate the morphological changes and mechanical properties of the dislocated ulnar nerve and monitor disease progress.

The role of ultrasonography in diagnosing acute closed volar plate injury of proximal interphalangeal joint.

BACKGROUND: Acute closed volar plate injury of the proximal interphalangeal joint (PIP) is a common hand injury. In the past, there were few objective evaluation imaging methods for the degree of volar plate injury. The purpose of this study was to investigate the role of high frequency ultrasonography in diagnosing volar plate injury, and to explore whether ultrasound can provide a beneficial guidance to clinical decision-making and appropriate treatment adopting through accurate US classification of volar plate injury. METHODS: From May 2019 to may 2022, 41 patients diagnosed with volar plate injury were included in this study. All patients underwent ultrasonography and X-ray examinations. The sonographic features were analyzed. A new kind of classification of volar plate injury based on ultrasonography findings was described. RESULTS: Either an injury of volar plate or an avulsion fracture of middle phalangeal base was identified clearly on ultrasonography, according to which volar plate injury could be divided into three types: A, B and C. Type A, avulsion fracture of the middle phalangeal base without volar plate rupture; Type B, full thickness tear of the volar plate without avulsion fracture; Type C, partial thickness tear of the volar plate. The average thickness of the three types of injured volar plate measured by ultrasound was 0.33 ± 0.05 cm, and the average thickness of the volar plate at the same site of the corresponding finger on the contralateral side was 0.22 ± 0.03 cm. There was significant difference between the two group (t = 11.823, p = 1.2476 *10^(-14)). CONCLUSIONS: High frequency ultrasonography could be a reliable, accurate, convenient and non-radioactive diagnostic imaging technique in the evaluation of acute closed volar plate injury of PIP. And ultrasound could provide a beneficial guidance to clinical decision-making and appropriate treatment adopting through accurate US classification.

Comparative analysis of ultrasound diagnosis and pathological characteristics of external jugular venous aneurysm.

PURPOSE: This study aimed to investigate the diagnosis of the external jugular venous aneurysm on color Doppler ultrasound and its relationship with pathological characteristics. METHODS: A retrospective analysis of 17 patients with external jugular venous aneurysm admitted to the Provincial Hospital Affiliated with Shandong First Medical University from May, 2010, to June, 2020, was performed. The color Doppler ultrasound characteristics of 17 patients with external jugular vein aneurysms were analyzed and summarized, which were then compared with postoperative pathological outcomes. RESULTS: All 17 patients with external jugular venous aneurysms were presented with cystic structures adjacent to and communicated with the external jugular vein. Color Doppler flow imaging showed a bidirectional venous flow signal in the communication between the cystic structure and the external jugular vein. Among the 17 patients, ultrasound diagnosis showed true venous aneurysm due to degenerative changes in the venous wall in 8 cases, venous pseudoaneurysm in 4 cases, and external jugular venous aneurysm in 5 cases, and postoperative pathology indicated degenerative changes in the venous wall in all 17 patients. CONCLUSION: Bidirectional blood flow at the communication between the cystic lesion and the external jugular vein on color Doppler ultrasound should not be the criterion for the diagnosis of external jugular venous pseudoaneurysm, which requires pathological support.

Comprehensive Analysis of the Sorafenib-Associated Druggable Targets on Differential Gene Expression and ceRNA Network in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the predominant pathological type of liver cancer. Several therapeutic treatments, including sorafenib and regorafenib, have only modestly improved survival in patients with HCC. The aim of this study was to investigate the expression profiles and the regulation of competitive endogenous RNAs (ceRNAs) of the sorafenib-related target genes in HCC. Based on clinical information and expression profiles of HCC clinical samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, shared differentially expressed genes (DEGs) were analyzed and identified. Sorafenib-associated DEGs (SADs) were obtained by intersecting the DEGs with the sorafenib target genes from SuperTarget database. The expression patterns of SADs were verified in the Oncomine database. The biological functions of the SADs were annotated by gene set enrichment analysis (GSEA). In addition, a ceRNA network associated with SADs was constructed. Long non-coding RNAs (lncRNAs) in network that were significantly associated with overall survival were identified as prognosis of patients by Cox regression analysis. Finally, the expression levels of prognostic genes in HCC tissues and cell lines were verified using qRT-PCR. Gene expression differential analysis yielded a total of 146 common DEGs were obtained, including 21 upregulated and 125 downregulated DEGs. Among them, ten SADs were detected to be differentially expressed between tumor and normal tissues, including AXL, CYP2C19, CYP2C8, CYP2C9, CYP3A4, FGFR2, GMNN, PDGFRA, and TTK. GSEA analysis grouped them into three categories by function. The first category (CYP2C19, CYP2C8, CYP2C9 and CYP3A4) and second category (GMNN, TTK and EGER2) had the opposite roles in the enriched terms and pathways, while the third class (AXL and PDGFRA) has enrichment terms and pathways that intersect with those of the first and second categories. A ceRNA network associated with SADs was also constructed including 49 lncRNAs, 14 miRNAs, and 8 mRNAs. Three of these lncRNAs, SNHG7, GAS5 and HCP5, were found upregulated in HCC tissues and to be independent predictors in HCC patients. Significant correlations were found in expression between the prognostic lncRNAs and SADs. Ten SADs were systematically identified using expression data from HCC and normal tissues from TCGA and GEO datasets. GSEA analysis provided us with insight into the function of SADs. In the future, we will continue to explore the mechanisms of coordinated regulation of SADs-related prognostic lncRNAs and SADs at the ceRNA axis level and their potential functions in the development of HCC.

Diagnostic value of high-frequency ultrasound for Poland syndrome.

BACKGROUND: The imaging diagnosis of Poland syndrome is mostly computed tomography (CT) or magnetic resonance imaging (MRI), whereas high-frequency ultrasound for the diagnosis of Poland syndrome is relatively rare. PURPOSE: To investigate the diagnostic value of high-frequency ultrasound for Poland syndrome. MATERIAL AND METHODS: A retrospective analysis of 15 patients diagnosed with Poland syndrome was performed, and the characteristics of ultrasound images were summarized. RESULTS: High-frequency ultrasound clearly depict the anatomical structures of each layer of the chest wall in patients with Poland syndrome. Ultrasonography mainly showed partial or total absence of the pectoralis major muscle on the affected side, and some of which were combined with the absence of the pectoralis minor muscle. The difference was statistically significant in the thickness of the affected chest wall compared with the healthy side (P < 0.01). Out of 15 cases with Poland syndrome, 11 were associated with ipsilateral brachydactyly or syndactyly, and high-frequency ultrasonography showed that the bifurcation position of the common palmar digital artery on the affected finger was lower than that on the healthy side. CONCLUSION: High-frequency ultrasound is an effective imaging method for the diagnosis of Poland syndrome.

HMGB1/TLR4 signaling pathway enhances abdominal aortic aneurysm progression in mice by upregulating necroptosis.

OBJECTIVE AND DESIGN: The age-associated increases in aseptic inflammation and necroptosis are closely related to the emergence of various age-associated diseases. METHODS: In this study, the role of HMGB1/TLR4-induced necroptosis in abdominal aortic aneurysm (AAA) formation was investigated. First, the levels of sterile inflammatory mediators (HMGB1, TLR4) and necroptosis markers were measured in the abdominal aortas of young and old C57BL/6JNifdc mice. We observed that sterile inflammatory mediators and necroptosis markers were greatly increased in the abdominal aortas of old mice. Then, angiotensin II (Ang II)-induced AAA model in APOE-/- mice was used in this study. Mice AAA models were treated with the RIP1 inhibitor necrostatin-1 (Nec-1) or the TLR4 inhibitor TAK-242, respectively. RESULTS: We found that HMGB1, TLR4, and necroptosis markers were elevated in old mice compared with those in young mice. Same elevation was also found in the development of AAA in APOE-/- mice. In addition, the necroptosis inhibitor Nec-1 alleviated Ang II-induced AAA development while downregulating the expression of HMGB1/TLR4. After blocking TLR4 with TAK-242, the expression of necroptosis markers decreased significantly, and the progression of AAA was also alleviated in APOE-/- mice. CONCLUSIONS: Our results indicated that HMGB1/TLR4-mediated necroptosis enhances AAA development in the Ang II-induced AAA model in APOE-/- mice and that TLR4 might be a potential therapeutic target for AAA management.

The role of ultrasonography in diagnosis of neuralgic amyotrophy.

OBJECTIVE: To investigate the value of high frequency ultrasound in diagnosis of neuralgic amyotrophy. MATERIALS AND METHODS: From January 2010 to December 2020, the ultrasonographic images of 117 patients with neuralgic amyotrophy diagnosed by the Department of Neurology and hand & foot surgery of Shandong Provincial Hospital Affiliated to Shandong First Medical University were retrospectively analyzed. The ultrasonographic features were summarized. RESULTS: High frequency ultrasound could clearly show the degree of the affected nerves: No ultrasonic findings were found in 12 cases (10%). The affected nerves were thickening and hypoechogenicity with loss of normal fascicular definition in 28 cases (24%). The affected nerves showed hourglass-like changes, including constriction and torsion in 77 cases (66%). In addition, ultrasound can determine the extent of the lesion, and microvascular imaging can display small blood flow signal within the nerve. There was a significant statistical difference between the diameter of the thickened nerve fascicle and the diameter of the nerve fascicle at the corresponding site of the contralateral normal limb. CONCLUSIONS: High frequency ultrasound is a valuable imaging method for diagnosis of neuralgic amyotrophy.

Study on the Crush Injury Model of the Sciatic Nerve in Rabbits by Conventional Ultrasound and Elastography.

BACKGROUND: The crush injury model of the sciatic nerve in rabbits is a common nerve injury model, but there is little literature on the evaluation of nerve stiffness by ultrasound elastography. PURPOSE: To explore the value of ultrasound elastography in diagnosing crush injury of the sciatic nerve in rabbits. MATERIALS AND METHODS: Forty cases of crush injury model of the sciatic nerve in rabbits were examined by conventional ultrasound and elastography. The sonographic manifestations and stiffness of the model were analyzed, and the regularity of nerve injury with time was summarized. RESULTS: Ultrasound could clearly show the location, range, and thickness of the injured nerve in this model. The thickness of the injured area reached a peak in the 2nd week and returned to normal thickness in the 8th week. The nerve stiffness of the injured area increased gradually with time. CONCLUSION: Conventional ultrasound combined with elastography can comprehensively and quantitatively evaluate the morphological changes and mechanical properties of the injured sciatic nerve in rabbits, which may be of great significance to the repair and rehabilitation of peripheral nerve crush injuries.

YiQiFuMai lyophilized injection attenuates cerebral ischemic injury with inhibition of neuronal autophagy through intervention in the NMMHC IIA-actin-ATG9A interaction.

BACKGROUND: YiQiFuMai lyophilized injection (YQFM) is derived from a traditional Chinese medicine prescription termed Shengmai San.YQFM is clinically applied to the treatment of cardiovascular and cerebrovascular diseases. It has been found that critical components of YQFM affect non-muscle myosin heavy chain IIA (NMMHC IIA), but its regulation in the excessive autophagy and the underlying mechanism has yet to be clarified. PURPOSE: To evaluate whether YQFM has neuroprotective effects on cerebral ischemia/reperfusion-induced injury by inhibiting NMMHC IIA-actin-ATG9A interaction for autophagosome formation. METHODS: The neuroprotective effects of YQFM were investigated in vivo in mice with middle cerebral artery occlusion/reperfusion (MCAO/R) (n = 6) by detecting neurological deficits, infarct volume, and histopathological changes. The NMMHC IIA-actin-ATG9A interaction was determined using immunofluorescence co-localization, co-immunoprecipitation, and proximity ligation assay. Rat pheochromocytoma (PC12) cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were used to mimic neurons in in vitro experiments. RESULTS: In MCAO/R model mice, YQFM (1.342 g/kg) attenuated brain ischemia/reperfusion-induced injury by regulating NMMHC IIA-actin-mediated ATG9A trafficking. YQFM (400 µg/ml) also exerted similar effects on OGD/R-induced PC12 cells. Furthermore, RNAi of NMMHC IIA weakened the NMMHC IIA-F-actin-dependent ATG9A trafficking and, therefore, attenuated the neuroprotective activities of YQFM in vitro. CONCLUSION: These findings demonstrated that YQFM exerted neuroprotective effects by regulating the NMMHC IIA-actin-ATG9A interaction for autophagosome formation. This evidence sheds new light on the potential mechanism of YQFM in the treatment of cerebral ischemia/reperfusion.

The role of ultrasonography in diagnosing hourglass-like fascicular constriction(s) of the anterior interosseous nerve.

BACKGROUND: In the past, the diagnosis of hourglass-like fascicular constriction(s) of the anterior interosseous nerve mostly depended on electrophysiological examination, by which the location could not be diagnosed. There are few studies on the evaluation of hourglass-like fascicular constriction(s) by ultrasonography. PURPOSE: To evaluate the role of ultrasonography in the diagnosis of hourglass-like fascicular constriction(s) of the anterior interosseous nerve. MATERIAL AND METHODS: A retrospective analysis of 12 patients with hourglass-like fascicular constriction(s) of the anterior interosseous nerve was carried out, and the characteristics of the high-frequency ultrasonographic images were summarized and compared with surgical exploration. RESULTS: The 12 cases of hourglass-like fascicular constriction(s) of the anterior interosseous nerve were all located in the median nerve of the distal upper arm, including nine cases of single hourglass-like fascicular constriction and three cases of multiple hourglass-like fascicular constrictions. High-frequency ultrasonography can accurately locate the hourglass-like fascicular constriction(s) of the anterior interosseous nerve and the extent of neuropathy. The ultrasonographic images of hourglass-like fascicular constriction(s) of the anterior interosseous nerve showed single or multiple hourglass-like change(s) in the median nerve of the distal upper arm. The nerve fascicles on both sides of the affected nerve with hourglass-like change thickened. CONCLUSIONS: High-frequency ultrasonography could be a reliable, convenient, and non-invasive diagnostic imaging method for hourglass-like fascicular constriction(s) of the anterior interosseous nerve.

The role of ultrasonography in the diagnosis of talocalcaneal coalitions.

BACKGROUND: Patients with talocalcaneal coalitions (TCC) often undergo computed tomography (CT). However, ultrasonography diagnosis of TCC has been seldom done according to the literature. PURPOSE: To investigate the accuracy of ultrasonography in diagnosing TCC compared to CT. MATERIAL AND METHODS: Ninety-seven consecutive patients with a clinical suspicion of TCC were included. Ultrasonography was used to assess the classification and complication of TCC. The main sonographic criteria for a positive diagnosis in cases of osseous coalition were the joint space between the medial surface of talar head and the underlying sustentaculum tali of calcaneus disappearing and being replaced by a continuous hyperechoic bony structure. In cases of fibrous coalition, ultrasonography revealed a reduced space of the joint associated with an irregular, angular appearance of its outline and hypoechoic fibrous tissue inside. These data were compared with CT findings. κ statistic was applied to determine the level of agreement. The sensitivity, specificity, positive and negative predictive values, accuracy, and Youden index of ultrasonography as a diagnostic method were assessed. RESULTS: Ultrasonography findings were positive in 20 of 97 patients with a clinical suspicion of TCC. The diagnosis was confirmed by CT in 21 patients. There were one false-positive result and two false-negative results by ultrasonography. The κ value was 0.907. The sensitivity, specificity, positive and negative predictive values, accuracy, and Youden index of ultrasonography were 90.5%, 98.7%, 95.0%, 97.4%, 96.9%, and 0.892, respectively. CONCLUSION: Ultrasonography could be a reliable, accurate, and non-radioactive diagnostic imaging method in diagnosis of patients with suspected TCC.

Surgical treatment of extensive hepatic alveolar echinococcosis using a three-dimensional visualization technique combined with allograft blood vessels: A case report.

RATIONALE: Hepatic alveolar echinococcosis (HAE) presents a high pathogenicity and case fatality rate. The main treatment for HAE is surgical resection. Giant lesions in the liver and invasion of the pathogen into the retrohepatic inferior vena cava are usually associated with a poor prognosis when radical resection cannot be performed. PATIENT CONCERNS: A 56-year-old man who underwent hydatidectomy 7 years prior noted a recurrence of HAE. He was subsidized and admitted to our hospital for the purpose of surgical treatment. DIAGNOSIS: By computed tomography, angiography and three-dimensional (3D) computed tomography reconstruction images, multiple, giant HAE with 75% stenosis was confirmed. INTERVENTIONS: With the 3D visualization technique, we designed the surgical plan and performed radical resection of the lesions, including the invaded inferior vena cava, and maximized retention of normal liver tissue. The abdominal aorta of an organ donor was used for vascular allograft reconstruction. OUTCOMES: The patient recovered gradually after the operation. He was followed up for 3 months, and the reconstructed vein patency was good. LESSONS: The 3D visualization technique combined with a blood vessel allograft allowed us to expand indications for radical resection of extensive HAE.

Exportin-5 SUMOylation promotes hepatocellular carcinoma progression.

Increasing evidence has shown that abnormal expression of XPO5 is found in many human cancers and acts as an oncoprotein in certain cancers. However, its functional role in hepatocellular carcinoma (HCC) remains unexplored. In our study, we found that XPO5 was highly expressed in HCC, which was associated with SUMO modification. Moreover, we found that XPO5 was SUMOylated by SUMO2 at K125. Functional experiments revealed that XPO5 SUMOylation could promote MHCC97H cell proliferation, migration and invasion. In addition, we found that the nuclear export of pre-miR-3184 was suppressed by SUMOylated XPO5. Moreover, PLCB1 was identified as the common target of miR-3184-5p and miR-3184-3p. The suppressed phenotype induced by miR-3184-5p and miR-3184-3p could be rescued by overexpression of PLCB1. Bioinformatics analysis showed that PLCB1 expression had a negative relationship with HCC patient survival. The inhibitory effects of MHCC97H cells resulted from abnormal XPO5 SUMO modification could be blocked by miR-3184 inhibitor or PLCB1 overexpression. In conclusion, our findings demonstrate a novel mechanism of XPO5 in HCC, that is, the SUMOylated XPO5 acts as an "oncogenic" role in MHCC97H cells proliferation, migration and invasion by controlling the nuclear-cytoplasm transportation of miR-3184, thus up-regulating PLCB1 expression.

NMMHC IIA triggers neuronal autophagic cell death by promoting F-actin-dependent ATG9A trafficking in cerebral ischemia/reperfusion.

Previous findings have shown that non-muscle myosin heavy-chain IIA (NMMHC IIA) is involved in autophagy induction triggered by starvation in D. melanogaster; however, its functional contribution to neuronal autophagy remains unclear. The aim of this study is to explore the function of NMMHC IIA in cerebral ischemia-induced neuronal autophagy and the underlying mechanism related to autophagy-related gene 9A (ATG9A) trafficking. Functional assays and molecular mechanism studies were used to investigate the role of NMMHC IIA in cerebral ischemia-induced neuronal autophagy in vivo and in vitro. A middle cerebral artery occlusion (MCAO) model in mice was used to evaluate the therapeutic effect of blebbistatin, a myosin II ATPase inhibitor. Herein, either depletion or knockdown of NMMHC IIA led to increased cell viability in both primary cultured cortical neurons and pheochromocytoma (PC12) cells exposed to oxygen-glucose deprivation/reoxygenation (OGD/R). In addition, NMMHC IIA and autophagic marker LC3B were upregulated by OGD/R, and inhibition of NMMHC IIA significantly reduced OGD-induced neuronal autophagy. Furthermore, NMMHC IIA-induced autophagy is through its interactions with F-actin and ATG9A in response to OGD/R. The NMMHC IIA-actin interaction contributes to ATG9A trafficking and autophagosome formation. Inhibition of the NMMHC IIA-actin interaction using blebbistatin and the F-actin polymerization inhibitor cytochalasin D significantly suppressed ATG9A trafficking and autophagy induction. Furthermore, blebbistatin significantly improved neurological deficits and infarct volume after ischemic attack in mice, accompanied by ATG9A trafficking and autophagy inhibition. These findings demonstrate neuroprotective effects of NMMHC IIA inhibition on regulating ATG9A trafficking-dependent autophagy activation in the context of cerebral ischemia/reperfusion.

NMMHC IIA Inhibition Ameliorates Cerebral Ischemic/Reperfusion-Induced Neuronal Apoptosis Through Caspase-3/ROCK1/MLC Pathway.

PURPOSE: Our previous studies have indicated that non-muscle myosin heavy chain IIA (NMMHC IIA) is involved in H2O2-induced neuronal apoptosis, which is associated with the positive feedback loop of caspase-3/ROCK1/MLC pathway. However, the neuroprotective effect of NMMHC IIA inhibition with an adeno-associated virus (AAV) vector after transient middle cerebral artery occlusion (MCAO) and its role in caspases-3/ROCK1/MLC pathway remain blurred. METHODS: Green fluorescent protein (GFP) and a small hairpin RNA targeting Myh9 (encoding NMMHC IIA) were cloned and packaged into the AAV9 vector. AAV-shMyh9 or control vector were injected into C57BL/6J mice four weeks prior to 60 min MCAO. Twenty-four hours after reperfusion, functional and histological analyses of the mice were performed. RESULTS: In this study, AAV-shMyh9 was used to down-regulate NMMHC IIA expression in mice. We found that down-regulation of NMMHC IIA could improve neurological scores and histological injury in ischemic mice. Ischemic attack also activated neuronal apoptosis, and this effect was partially attenuated when NMMHC IIA was inhibited by AAV-shMyh9. In addition, AAV-shMyh9 significantly reduced cerebral ischemic/reperfusion (I/R)-induced NMMHC IIA-actin interaction, caspase-3 cleavage, Rho-associated kinase1 (ROCK1) activation and myosin light-chains (MLC) phosphorylation. CONCLUSION: Consequently, we showed that AAV-shMyh9 inhibits I/R-induced neuronal apoptosis linked with caspase-3/ROCK1/MLC/NMMHC IIA-actin cascade, which has also been confirmed to be a positive feedback loop. These findings put some insights into the neuroprotective effect of AAV-shMyh9 associated with the regulation of NMMHC IIA-related pathway under ischemic attack and provide a therapeutic strategy for ischemic stroke.

Evaluation of miR-331-3p and miR-23b-3p as serum biomarkers for hepatitis c virus-related hepatocellular carcinoma at early stage.

BACKGROUND AND AIMS: This study aimed to investigate the diagnostic values of serum miR-331-3p and miR-23b-3p as tumor markers for the diagnosis of hepatocellular carcinoma (HCC) at early stage. METHODS: A total of 191 subjects were enrolled and consisted of 45 healthy controls (HC), 106 hepatitis c virus (HCV)-related chronic liver disease (CLD) patients, and 40 early-stage HCC patients. CLD patients were subdivided according to Metavir fibrosis-scoring. Serum miR-331-3p and miR-23b-3p were measured. The area under curves (AUC) was calculated for each microRNA and compared with that for alpha-fetoprotein (AFP) in the detection of HCC at early stage. RESULTS: Serum miR-331-3p was significantly higher in early-stage HCC than that in CLD and HC respectively, and it decreased significantly after surgery in early-stage HCC. Contrarily, serum miR-23b-3p was significantly lower in early-stage HCC and increased significantly after surgery. Further, receiver operating characteristic analysis demonstrated AUC was 0.806 (95%CI: 0.728-0.883; sensitivity: 85.85%, specificity: 65.00%) for serum miR-23b-3p in discriminating early-stage HCC from CLD patients, higher than that for AFP (AUC:0.660, 95%CI: 0.556-0.764; sensitivity: 70.00%, specificity: 56.60%). In discrimination early-stage HCC from severe fibrosis/cirrhosis (F3 + F4) patients, both miR-23b-3p (AUC: 0.796, 95%CI: 0.703-0.889; sensitivity: 85.11%, specificity: 65.00%) and miR-331-3p (AUC:0.832, 95%CI: 0.812-0.953; sensitivity: 75.00%, specificity: 85.11%) had better diagnostic performances than AFP (AUC:0.632, 95%CI: 0.512-0.753; sensitivity: 50.00%, specificity: 55.32%). Serum miR-331-3p levels also showed a significant correlation with BCLC stages of HCC. CONCLUSION: Serum miR-331-3p and miR-23b-3p could be used as novel invasive biomarkers in the early detection of HCC in high-risk patients.