[Value of ultrasonography in diagnosis and classification of Masson's tumor].

A retrospective analysis was performed on 11 cases of Masson's tumor admitted to Liaocheng People's Hospital from January 2010 to July 2021. Among them, there were 4 males and 7 females, aged from 14 to 62 years, with a medical history of 1 to 24 months. All of the patients complained of touching the mass under the skin. In this group, 9 cases were pure form, 1 case was mixed form and 1 case was extravascular form. Ultrasound imaging can reflect the characteristics of Masson's tumor to a certain extent, which has a certain value in the diagnosis, classification and differential diagnosis.

Annual prevalence estimation of lymphatic malformation with a cutaneous component: observational study of a national representative sample of physicians.

BACKGROUND: Lymphatic malformations (LMs) represent a potentially life-threatening, rare disease of the lymphatic system characterized by development of abnormal vessels, outpouchings, or cysts filled with lymphatic fluid. There are three morphologic types of LMs based on the size of the individual cysts: macrocystic (typically > 2 cm), microcystic (generally < 2 cm), and mixed (includes aspects of both). Macrocystic LMs typically exist beneath the skin and often can involve vascular components and/or organs. Microcystic LMs often have a cutaneous component and clinically present with lymphorrhea, bleeding, pain, itching, malodor, and functional deficits. There are no treatments approved by the US Food and Drug Administration (FDA) for either macrocystic or microcystic lymphatic malformations. The totality of the epidemiologic literature for LM is limited to the incidence of the disease among various birth cohorts. This is the first nationally representative study to estimate the national managed prevalence for patients with microcystic LM or combined LM with a cutaneous component annually across physician specialties likely to manage this condition. We conducted a retrospective observational survey of a nationally representative sample of patient-care physicians in the United States most likely to manage lymphatic malformations with a cutaneous component (LMC). Once recruited, target physicians participated via an electronic questionnaire. We weighted study physician self-estimates of the number of LMC patients treated in the past 12 months to reflect the specialists' corresponding proportion in the national universe. All patient information was anonymous; no personally identifiable information was collected. RESULTS: Of the 420 physicians who visited the study website, 316 agreed to be screened and to participate (75.2% participation rate). Our survey results indicated the estimated number of unique annually managed LMC patients by target specialists is 79,920 (CI 66,600-93,250). This number corresponds to managed prevalence of 24.1 LMC patients per 100,000 population (CI 19.6/100,000-28.4/100,000). CONCLUSIONS: The study indicates that while rare, LMC affects a substantial number of people in the US (79,920) who are being managed by one or more specialists. By better understanding the prevalence of people living with LMC who require treatment, efforts to both increase disease awareness and to identify underserved populations in need of potential new treatments can be better focused.

The role of ultrasonography in the diagnosis of persistent sciatic artery.

AIM: To investigate the accuracy of ultrasonography in the diagnosis of persistent sciatic artery (PSA) compared to computed tomography angiography (CTA). MATERIALS AND METHODS: From May 2002 to Dec 2018, 61 consecutive patients seen at Shandong Medical Imaging Research Institute with a clinical suspicion of PSA were included. Ultrasonography was used to assess the abdominal and lower-limb arteries. The main sonographic criteria for a positive diagnosis were the visualisation of PSA, the enlarged internal iliac artery, and abnormality of common femoral artery and superficial femoral artery. These data were compared with CTA findings. Kappa statistics 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 16 of 61 patients with a clinical suspicion of PSA. The diagnosis was confirmed by CTA in 17 patients. There was one false-positive result and two false-negative results at ultrasonography. The kappa value was 0.875. The sensitivity, specificity, positive and negative predictive values, accuracy, and Youden index of ultrasonography were 88.2%, 97.7%, 93.8%, 95.6%, 95.1% and 0.859, respectively. CONCLUSIONS: Ultrasonography could be a reliable, accurate, and non-invasive diagnostic imaging method in the diagnosis of patients with suspected PSA.

nab-Paclitaxel-Based Therapy in Underserved Patient Populations: The ABOUND.70+ Study in Elderly Patients With Advanced NSCLC.

The phase 4 ABOUND.70+ trial assessed the safety and efficacy of nab-paclitaxel/carboplatin continuously or with a 1-week break between cycles in elderly patients with advanced non-small cell lung cancer (NSCLC). Patients ≥70 years with locally advanced/metastatic NSCLC were randomized 1:1 to first-line nab-paclitaxel days 1, 8, 15 plus carboplatin day 1 of a 21-day cycle (21d) or the same nab-paclitaxel/carboplatin regimen with a 1-week break between cycles (21d + break; 28d). The primary endpoint was the percentage of patients with grade ≥ 2 peripheral neuropathy (PN) or grade ≥ 3 myelosuppression. Other key endpoints included progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). A total of 143 patients were randomized (71 to 21d, 72 to 21d + break). The percentage of patients with grade ≥ 2 PN or grade ≥ 3 myelosuppression was similar between the 21d and 21d + break arms (76.5 and 77.1%; P = 0.9258). Treatment exposure was lower in the 21d arm compared with the 21d + break arm. Median OS was 15.2 and 16.2 months [hazard ratio (HR) 0.72, 95% CI 0.44-1.19; P = 0.1966], median PFS was 3.6 and 7.0 months (HR 0.48, 95% CI 0.30-0.76; P < 0.0019), and ORR was 23.9 and 40.3% (risk ratio 1.68, 95% CI 1.02-2.78; P = 0.0376) in the 21d and 21d + break arms, respectively. In summary, the 1-week break between treatment cycles significantly improved PFS and ORR but did not significantly reduce the percentage of grade ≥ 2 PN or grade ≥ 3 myelosuppression. Overall, the findings support the results of prior subset analyses on the safety and efficacy of first-line nab-paclitaxel/carboplatin in elderly patients with advanced NSCLC.

miR-135a inhibits glioma cell proliferation and invasion by directly targeting FOXO1.

OBJECTIVE: To investigate the potential function of miR-135a in glioma. PATIENTS AND METHODS: A total of 50 pairs of glioma tissue samples and para-carcinoma tissue samples were collected. Human glioma cell line (U251) and normal human astrocyte (NHA) were cultured. The expression of RNA and protein was detected by quantitative Real time-polymerase chain reaction (qRT-PCR) and Western blot, respectively. Cell proliferation assay and transwell assay were used to detect the activities of proliferation and invasion. Luciferase reporter assays were carried out to determine the binding efficiency between forkhead box O1 (FOXO1) and miR-135a in U251 cells. RESULTS: qRT-PCR results showed that miR-135a expression was significantly reduced while FOXO1 was up-regulated in glioma tissues. miR-135a overexpression in U251 cells could prominently inhibit proliferation and invasion according to the transwell assays. Moreover, FOXO1 was recognized as the target for miR-135a and may partially reverse the functions of miR-135a in U251 cells. CONCLUSIONS: We showed that miR-135a inhibits glioma cell proliferation and invasion by down-regulating the target gene FOXO1.

Gemcitabine and cisplatin for treatment of lung cancer in vitro and vivo.

OBJECTIVE: To evaluate the antitumor activity of gemcitabine (GEM), cisplatin (DDP) as well as the combination of these two agents in lung cancer cells and mice. MATERIALS AND METHODS: The cell viability was evaluated by the CCK-8 assay. Cell apoptosis was measured by flow cytometry assay and Hoechst staining. The protein expression of VEGF, VEGFR2, Ang II, AT1R, and ACE2 was examined by Western blotting. The effect of GEM and DDP on tumor growth and survival time was also measured in lung cancer mice in vivo. RESULTS: The results revealed that alone or combined administration of GEM and DDP could inhibit the growth, induce apoptosis and apoptotic body formation of A549 cells compared with control cells, with the most significance detected in a combination of GEM and DDP administration. It is indicated that combined administration of GEM and DDP could delay the progress of tumor formation in nude mice. The cell apoptosis- and angiogenesis-related proteins expressions were decreased both in A549 cells and lung cancer mice. CONCLUSIONS: GEM plus DDP can be an option for patients with lung cancer treatment. However, further prospective evaluation and randomized trials are to provide more accurate information through clinical trials.

The significance of S100ß protein on postoperative cognitive dysfunction in patients who underwent single valve replacement surgery under general anesthesia.

OBJECTIVE: To analyze the effect of S100ß protein on postoperative cognitive dysfunction (POCD) in patients who underwent single valve replacement surgery. PATIENTS AND METHODS: Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were applied to evaluate 178 patients who underwent single valve replacement surgery under general anesthesia from June 2014 to December 2015. Patients were assessed 1 day before surgery and on postoperative days 2 and 9. Thirty-two patients were identified as having postoperative cognitive dysfunction (the POCD group), while 146 cases did not experience POCD (the control group). A total of 155 healthy adult volunteers from the Medical Center were simultaneously chosen (healthy comparison group). Serum S100ß levels from the three groups of patients were measured by ELISA. RESULTS: In the POCD group, serum S100ß levels were significantly higher than those of the control group and healthy comparison group (p < 0.05). The postoperative length of stay in the hospital for patients in the POCD group was significantly increased (p < 0.05). CONCLUSIONS: The expression of serum S100ß in patients with POCD was significantly increased. S100ß may represent a potential target for the diagnosis and treatment of cognitive dysfunction after cardiac surgery under general anesthesia.

RCN1 suppresses ER stress-induced apoptosis via calcium homeostasis and PERK-CHOP signaling.

Endoplasmic reticulum (ER) stress is caused by the disturbance of ER homeostasis and leads to the activation of the unfolded protein response (UPR), which alleviates stress at an early stage and triggers apoptosis if homeostasis fails over a prolonged timeframe. Here, we report that reticulocalbin 1 (RCN1), a member of the CREC family, is transactivated by nuclear factor kappa B (NF-κB) during ER stress and inhibits ER stress-induced apoptosis. The depletion of RCN1 increases the UPR during drug-induced ER stress by activating PRKR-like ER kinase-CCAAT/enhancer-binding protein-homologous protein (PERK-CHOP) signaling, thus inducing apoptosis. Furthermore, we found that the first two EF-hand calcium-binding motifs of RCN1 specifically interact with inositol 1,4,5-trisphosphate (IP3) receptor type 1 (IP3R1) on loop 3 of its ER luminal domain and inhibit ER calcium release and apoptosis. Together, these data indicate that RCN1, a target of NF-κB, suppresses ER calcium release by binding to IP3R1 and decreases the UPR, thereby inhibiting ER stress-induced apoptosis.

Direct sequencing of mutations in the copper-transporting P-type adenosine triphosphate (ATP7B) gene for diagnosis and pathogenesis of Wilson's disease.

Copper-transporting P-type adenosine triphosphatase (ATP7B) has been identified as the pathogenic gene in hepatolenticular degeneration, or Wilson's disease (WD). The aim of this study was to explore the correlation between genetic mutations and the clinical profile of WD, and to discuss the value of mutation examination in its diagnosis for providing a scientific basis for the development of a method to examine genetic mutations. Sixty-eight Chinese Han patients with WD and 20 controls were included in this study. The ATP7B gene in DNA extracted from patient blood samples was amplified by PCR and sequenced. These sequences were compared against corresponding gene sequences obtained from healthy controls to statistically analyze the genetic mutations. Five of the nineteen mutations in ATP7B were newly detected mutations; moreover, 8 of these mutations were polymorphic (2 were newly identified). The Arg778Leu and Pro992Leu mutations in exons 8 and 13 were detected at the highest mutation frequencies of 25.74 and 16.91%, respectively. The frequencies of all other mutations were below 5%. However, the clinical manifestations of WD did not differ significantly in patients with the Arg778Leu and Pro992Leu mutations. Therefore, these mutations were considered as hotspot mutations in Chinese WD patients. However, we observed no significant correlation between these genetic types and the clinical symptoms of WD. The correlation between the mutation genotype and disease phenotype remains to be elucidated. In conclusion, the highly sensitive and specific direct DNA sequencing method can be used to screen for the causative genes of WD.

[Analysis on the nuclear division index of peripheral blood lymphocytes in the 281 general population of Anhui, China].

OBJECTIVE: To investigate the reference range and influeing factors of the nuclear division index (NDI) of peripheral blood lymphocyte in Chinese general population in Anhui province. METHODS: We selected 281 subjects from the general poulation in Anhui province, without occupational exposure to genetic toxicants and no chronic disease history. We used questionnaires to collect occupational history, age, gender, region, body mass index, smoking, and alcohol drinking status etc. NDI was measured by cytokinesis block micronucleus assay in peripheral blood lymphocytes, and the related factors were also analyzed. And NDI was used as the dependent variable, age, gender and other factors as independent variables to conduct stepwise multiple linear regression. RESULTS: We found the data of NDI according with normal distribution, and the nuclear division index was 1.71±0.22, the minimum value was 1.10 while the maximum was 2.36. The results showed that NDI value of the males (1.67±0.20) were lower than that of the females (1.76±0.24), the difference was statistically significant (t=-3.65, P<0.001); current smokers NDI (1.66±0.18) lower than non-smokers (1.73±0.24) differences were statistically significant (t=3.06, P=0.002); the NDI of drinking groups (1.66±0.20) was lower than that of non-drinking population (1.74±0.23), the differences was statistically significant (t=3.15, P=0.002); Using multiple stepwise linear regression calibration factors and found that gender was an independent factor of NDI (ß=0.098, Sx=0.027, t=3.66, P< 0.001). CONCLUSION: We set the reference value on the nuclear division index among general population of survey areas in this study, it could provide a reference for similar studies and will provide reference for better evaluation of the effects of hazards on the body.

Oral pristinamycin for the treatment of resistant Gram-positive infections in patients with cancer: Evaluation of clinical outcomes.

Pristinamycin has been used to treat a range of Gram-positive infections, but reported experience in patients with malignancy is limited. This study aimed to evaluate the use of pristinamycin in patients with cancer at an Australian centre. All patients commenced on oral pristinamycin therapy at the Peter MacCallum Cancer Centre between January 2005 and December 2014 were identified using the hospital pharmacy dispensing system. Information on demographics, co-morbidities, cancer diagnosis, infection characteristics, pristinamycin regimen, pristinamycin tolerability and outcomes was collected. The median duration of follow-up was 398 days. In total, 26 patients received pristinamycin, with median age of 61 years and a male predominance (65%). Underlying diagnoses were haematological malignancies (50%) and solid tumours (50%). Pathogens included 13 meticillin-resistant Staphylococcus aureus, 6 vancomycin-resistant Enterococcus faecium, 4 meticillin-resistant Staphylococcus epidermidis, 2 meticillin-susceptible S. aureus and 1 vancomycin-susceptible E. faecium. Infection sites were osteomyelitis (6), skin and soft-tissue (4), intra-abdominal/pelvic abscess (4), bloodstream (3), empyema (3), endocarditis/endovascular (3), prosthesis-related infection (2) and epididymo-orchitis (1). One patient ceased pristinamycin due to nausea. Regarding outcome, 13 patients (50%) were cured of infection, 8 (31%) had suppression and 5 (19%) had relapse. Relapses included 1 endovascular infection, 2 episodes of osteomyelitis, 1 pelvic abscess and 1 skin and soft-tissue infection. Overall, 81% of patients achieved cure or suppression of antibiotic-resistant or complex Gram-positive infections, consistent with published experience in non-cancer populations. A favourable tolerability profile makes oral pristinamycin a viable treatment option, particularly in settings where outpatient management of cancer is the objective.

Predicting the maturity of haemodialysis arteriovenous fistulas with colour Doppler ultrasound: a single-centre study from China.

AIM: To explore the optimal vascular diameter and blood flow measured by ultrasound to predict fistula maturity in Chinese patients. MATERIALS AND METHODS: One hundred and thirty-two patients were enrolled in the study. The blood flow and the diameters of the brachial artery, radial artery, and cephalic vein were analysed according to clinical outcomes. The performances of blood flow, cephalic vein diameter, and the two factors combined in predicting fistula maturity were evaluated and the optimal cut-off values for Chinese patients were determined. RESULTS: During a 6 month follow-up, 113 fistulas were classified as mature and 19 fistulas were classified as failure. In both groups, the diameters of the brachial and radial arteries increased gradually within 2 weeks post-surgery (p<0.05), and cephalic vein diameter and blood flow increased within 4 weeks post-surgery (p<0.05). The blood flow of the failure group was significantly lower than that of the mature group from the first day after creation. The area under the receiver operating characteristic (ROC) curve was 0.95 (529 ml/min, the optimal cut-off value) for blood flow, 0.83 (5.2 mm) for cephalic vein diameter, and 0.96 for the two factors combined in predicting fistula maturity. CONCLUSIONS: For Chinese patients, blood flow >529 ml/min could be used to predict fistula maturity and cephalic vein diameter >5.2 mm could be a supplement when necessary.

Cab45S promotes cell proliferation through SERCA2b inhibition and Ca2+ signaling.

Cytosolic Ca(2+), closely related to endoplasmic reticulum (ER) Ca(2+), plays a critical role in regulating cell proliferation and tumorigenesis. However, the role of ER lumen proteins in regulating cytosolic Ca(2+) level remains poorly understood. Here, we find that the Cab45S, localizes in the ER lumen, inhibits sarco/ER Ca(2+)-ATPase 2b (SERCA2b) activity through its first EF-hand domain directly binding to the intra-lumenal loop 4 of SERCA2b, and reduces ER Ca(2+). STIM1 activation, induced by the Cab45S-dependent drop in ER Ca(2+), together with the upregulation of the plasma membrane Ca(2+) channel TRPC1 ultimately increases extracellular Ca(2+) influx. Furthermore, increased cytosolic Ca(2+) level elicits Ca(2+)-NFAT signaling and promotes cell proliferation. Consistently, in cervical carcinoma patients, Cab45S is upregulated. Thus, our data reveal that the ability of Cab45S to inhibit SERCA2b activity is crucial for its role as a modulator of cell proliferation and tumor growth.

Role of adrenal vein sampling in primary aldosteronism: the Monash Health experience.

BACKGROUND: Adrenal vein sampling (AVS) is useful for distinguishing unilateral versus bilateral hypersecretion in primary aldosteronism (PA), but is technically challenging. Furthermore, the use of adrenocorticotropic hormone (ACTH)-stimulation in AVS is controversial. We implemented a Monash Health-specific AVS protocol in 2010. AIM: The audit aimed to: (i) examine the impact of a dedicated protocol on success rates of AVS at a tertiary referral centre; (ii) evaluate the impact of AVS on sub-typing of PA; and (iii) assess the utility of ACTH stimulation in AVS. METHODS: AVS was performed on patients with PA confirmed by positive saline suppression testing (aldosterone level >140 pmol/L post-saline infusion), with sequential sampling of adrenal and peripheral veins, pre- and post-ACTH infusion. Patients with unilateral aldosterone-producing adenoma diagnosed on successful AVS were referred for adrenalectomy. RESULTS: Between 2010 and 2014 inclusive, a total of 28 AVS procedures was performed, with complete pre- and post-ACTH data for 19 procedures. Bilateral successful cannulation rates improved post-implementation of our protocol (61% vs 41%). Of the patients, 32% had discordant imaging and AVS results: four patients with unilateral adenomas did not lateralise on AVS and were managed medically; four patients with bilateral or no adenomas on imaging, lateralised on AVS and had surgery. Overall, use of ACTH did not increase successful cannulation and tended to mask lateralisation. CONCLUSION: AVS is crucial in subtype classification of PA and should be performed by a dedicated radiologist with a standardised protocol. AVS outcomes were not improved with the use of ACTH stimulation.

Numb induces e-cadherin adhesion dissolution, cytoskeleton reorganization, and migration in tubular epithelial cells contributing to renal fibrosis.

Numb, an endocytic protein, is involved in both neural differentiation and protein post-endocytic trafficking. Although negative Numb expression has been linked to human mammary carcinomas, little is known about its expression and functions in other diseases. In the present study, we observed that Numb is expressed in renal tubule epithelia and its expression is increased in the fibrotic kidney in vivo. We determined that in proximal tubular epithelial cells (NRK52E cells), TGF-ß1 induces the expression of Numb and ectopic expression of Numb leads to dissolution of E-cadherin adhesion, reorganization of cytoskeleton, activation of Rac1 and Cdc42, and enhancement of migration. Either knockdown of α-adaptin or overexpression of Numb asparagine-proline-phenylalanine (NPF) mutant interferes with AP-2 dependent endocytosis and rescues Ecadherin level in NRK52E cells. Moreover, knockdown of integrin ß1 or α-adaptin, and overexpression of a Numb dominant-negative form (Numb phosphotyrosine binding [PTB] domain) impair integrin endocytosis, and markedly inhibit Numb-induced cell migration and activation of Rac1 and Cdc42. Taken together, our work identifies Numb as an important player in renal fibrosis, by regulating epithelial-to-mesenchymal transition (EMT) process including E-cadherin adhesion dissolution, actin reorganization, and migration enhancement in NRK52E cells.

Effect of integrin combined laminin on peripheral blood vessel of cerebral infarction and endogenous nerve regeneration.

The third Chinese nationwide survey on causes of death states that cerebrovascular disease, accounting for 22.45% of total deaths, ranks as the first cause of death among rural and urban residents. It has become a serious public health problem since it has the highest disability and fatality rate among single diseases. Cerebral infarction is the most common cerebrovascular disease. In order to enhance the treatment response of cerebral infarction, this paper established male Sprague Dawley (SD) rat reperfusion model with 2 h of cerebral artery embolism by suture method. Neurological function deficit was scored according to rat improvement 24 h after model establishment, and 50 rats with scores between 10 and 13 were included in an ultimate experiment and were randomly divided into 5 groups: undisturbed control group, vascular endothelial growth factor (VEGF) up-regulated vessel group, endostatin down-regulated vessel group, ventricle injected Cxc Chemokin Receptor 4 (CXCR4) antibody group, ventricle injected α6ß1 antagonist (GoH3 antibody) group, respectively. The experiment was initiated after grouping and measurement of the relative data. The obtained results showed that the behavioral recovery of the VEGF group was more obvious compared with the control group, and the differences were statistically significant. The research was carried out using decreased modified neurological severity scores (mNSS), and the time a rat took to remove a pasted object. However, the behavioral recovery in the endostatin group, anti-CXCR4 group and GoH3 group was slow, and the difference was statistically significant, which showed as slowly decreased mNSS scoring and inconspicuous improved time of a rat removing a sticker. Compared with the control group, the number of peripheral BrdU+/ vWF+ cells of rat cerebral infarction in the VEGF group increased, and the peripheral VEGF expression quantity of cerebral infarction increased, thus the difference was statistically significant. However, cells in the endostatin group, anti-CXCR4 group, and GoH3 group were fewer and VEGF expression was reduced, and the difference was statistically significant. All these findings suggest that the promotion of angiogenesis after cerebral infarction can better provide the vascular niche for the proliferation, migration and differentiation of neural stem/progenitor cells (NSPCs), thereby further promoting endogenous nerve regeneration. NSPCs can always closely connect with vessels through the interaction of integrin α6ß1 and laminin; furthermore, under the support provided by the vascular niche and the chemotaxis of stromal cellderived factor (SDF-1), NSPCs can migrate from the subventricular zone (SVZ) to the periphery of infarction.