Search

Background/Objectives: The purpose of this study was to develop the gemcitabine-loaded drug-eluting beads (G-DEBs) for transarterial chemoembolization (TACE) in rabbit renal tumors and to evaluate their antitumor effect using 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/X-ray computed tomography (18F-FDG PET/CT). Methods: DEBs were prepared by polyvinyl alcohol-based macromer crosslinked with N-acryl tyrosine and N,N′-methylenebis(acrylamide). Gemcitabine was loaded through ion change to obtain G-DEBs. Their particle size and drug release profile were characterized. VX2 tumors were implanted in the right kidney of rabbits to establish the renal tumor model. The tumor-bearing rabbits received pre-scan by 18F-FDG PET/CT, followed by targeted transarterial injection of G-DEBs under digital subtraction angiography (DSA) guidance. The rabbits received another 18F-FDG PET/CT scan 10 or 14 days after the treatment. The therapeutic effect was further validated by histopathological analysis of the dissected tumors. Results: The average particle size of the microspheres was 58.06 ± 0.50 µm, and the polydisperse index was 0.26 ± 0.002. The maximum loading rate of G-DEBs was 18.09 ± 0.35%, with almost 100% encapsulation efficiency. Within 24 h, GEM was eluted from G-DEBs rapidly and completely, and more than 20% was released in different media. DSA illustrated that G-DEBs were delivered to rabbit renal tumors. Compared with the untreated control group with increased tumor volume and intense 18F -FDG uptake, the G-DEBs group showed significant reductions in tumor volume and maximum standard uptake value (SUVmax) 10 or 14 days after the treatment. Histopathological analysis confirmed that the proliferating area of tumor cells was significantly reduced in the G-DEBs group. Conclusions: Our results demonstrated that G-DEBs are effective in TACE treatment of rabbit VX2 renal tumors, and 18F-FDG PET/CT provides a non-invasive imaging modality to monitor the antitumor effects of TACE in renal tumors. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Oculopharyngodistal myopathy type 4 (OPDM4) arises from a CGG repeat expansion in the 5′ UTR of the RILPL1 gene. Reported cases of OPDM4 have been limited. The aim of this study was to investigate the clinical and myopathological characteristics of OPDM4 patients with advanced disease. Methods: We assessed a total of 8 affected and 12 unaffected individuals in an OPDM4 family with autosomal dominant inheritance. Muscle biopsy tissue from the proband underwent histological, enzyme histochemical, and immunohistochemical stains, and electron microscopy analysis. Whole exome sequencing and repeat primer PCR (RP‐PCR) were conducted to investigate underlying variants. Results: OPDM4 patients displayed a progressive disease course. Most experienced lower limb weakness and diminished walking ability in their 20s and 30s, followed by ptosis, ophthalmoplegia, swallowing difficulties, and dysarthria in their 30s to 50s, By their 50s to 70s, they became non‐ambulatory. Muscle magnetic resonance imaging (MRI) of the proband in advanced disease revealed severe fatty infiltration of pelvic girdle and lower limb muscles. Biopsied muscle tissue exhibited advanced changes typified by adipose connective tissue replacement and the presence of multiple eosinophilic and p62‐positive intranuclear inclusions. Immunopositivity for the intranuclear inclusions was observed with anti‐glycine antibody and laboratory‐made polyA‐R1 antibody. RP‐PCR unveiled an abnormal CGG repeat expansion in the 5′ UTR of the RILPL1 gene. Discussion: The clinical and radiological features in this family broaden the phenotypic spectrum of OPDM4. The presence of intranuclear inclusions in the proliferative adipose connective tissues of muscle biopsy specimens holds diagnostic significance for OPDM4 in advanced disease. [ABSTRACT FROM AUTHOR]

Titanium alloy is widely used as oil drill pipe material because of its light weight, high strength, good toughness, corrosion resistance, fatigue resistance, and good process performance. However, due to its low hardness, poor wear resistance, serious oxidation at high temperature (700 °C), and difficulty in lubrication, in oil and gas field exploration and development drilling, especially in deep wells, high displacement wells, horizontal wells, and highly deviated wells, wear and tear are prone to occur. The application and development of titanium alloys are greatly limited. This paper introduces the research status of the common surface modification technologies of titanium alloys, such as laser cladding, magnetron sputtering, plasma spraying, micro arc oxidation, etc. It points out the improvement effect of various modification technologies on the wear resistance and high-temperature oxidation resistance of titanium alloys and discusses the advantages and disadvantages of various modification technologies. A proposed method for enhancing the wear resistance and high-temperature oxidation resistance of titanium alloys was finally introduced, and its potential for future development was investigated. [ABSTRACT FROM AUTHOR]

Objective To investigate the risk factors for pathological upstaging of clinical T2N0M0 esophageal carcinoma by analyzing the clinicopathological data. Methods We collected 149 patients with clinical T2N0M0 esophageal squamous carcinoma who underwent minimally invasive esophagectomy with two-field lymph node dissection. Univariate and multivariate Logistic regression analyses were performed to identify the factors related to pathologic upstaging. Results There were 59 (39.6%) cases of pathologic T2N0M0; 23(15.4%) cases were downstaged; 67(45%) cases were upstaged; 42(28.2%) cases were pathological T upstaged; and 45(30.2%) cases had lymph node metastasis. Both T upstaging and lymph node metastasis occurred in 12.8% patients. Univariate analysis showed that tumor length, depth of infiltration, differentiation degree and pathological morphology were related to T upstaging and the influencing factors of lymph node metastasis were tumor length and depth of infiltration (P < 0.05). Multivariate analysis revealed that tumor length, depth of infiltration and differentiation degree were risk factors for T upstaging and the factors influencing lymph node metastasis were tumor length, degree of differentiation and lesion location (P < 0.05). Conclusion Clinical staging of T2N0M0 esophageal cancer remains inaccurate. Tumor length, depth of infiltration and differentiation degree are risk factors for T upstaging. The factors influencing lymph node metastasis are tumor length, degree of differentiation and lesion location.

Background18F-Flutemetamol (18F-FMM) PET/CT imaging has been widely applied to the diagnosis of mild cognitive impairment and Alzheimer's disease.PurposeThis study aims to explore the distributions of 18F-FMM in different brain regions of mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients and the factors that may affect the combination of 18F-FMM, evaluating the use of 18F-FMM PET/CT imaging in the diagnosis of MCI and AD patients.MethodsFrom July 2020 to April 2021, 24 subjects with MCI (12 males, 12 females, aged of (70.54±9.27) years old), 25 subjects with AD (11 males, 14 females, aged (70.56±7.30) years old) and 9 subjects as normal controls (NC, 2 males, 7 females, aged (57.67±9.00) years old) were recruited from Shanghai. The 18F-FMM PET/CT brain imaging of all subjects were qualitatively and semi-quantitatively analyzed by visual evaluation and standardized uptake value ratio (SUVR), respectively. Student's t-test, one-way analysis of variance and rank sum test were used for the comparison of quantitative variables. Pearson's chi-squared test and Fisher's exact test were used for the comparison of qualitative variables. The diagnostic efficiency was obtained by ROC curve. Multiple linear regression analysis was used to analyze the factors that might affect the combination of 18F-FMM.ResultsThe positive rate of visual assessment was significantly different in NC, MCI and AD groups (χ2=26.85, p < 0.001), and significant differences existed statistically in SUVR of all brain regions among the three groups (H value: 11.54~19.34, F value: 7.43, 11.48, all p < 0.01). The mean values of SUVR in the whole brain of the three groups were statistically different (Z value: -3.87, -2.79, -2.45, all p < 0.016 7). Compared with MCI group, the positive rate in occipital lobe, temporal lobe, parietal lobe and posterior cingulate gyrus was statistically significant (χ2=7.53~10.89, all p < 0.01). With respect to NC, SUVR of all brain regions was lower than that in AD, while SUVR of temporal lobe, frontal lobe and precuneu were lower than that in MCI. Meanwhile, SUVR of occipital lobe, temporal lobe, frontal lobe and parietal lobe in MCI were lower than that in AD. Receiver operating characteristic (ROC) curves showed that the SUVR value of temporal lobe and the mean value of SUVR in the whole brain had the ability to distinguish NC, MCI and AD in sequence. Multiple linear regression analysis showed that cognitive level was significantly negatively correlated with 18F-FMM SUVR in different brain regions.Conclusion18F-FMM PET/CT brain imaging could reflect the cognitive level of middle-aged and elderly people intuitively and has clear diagnostic value for MCI and AD.

Introduction: Spinocerebellar ataxia type 36 (SCA36) is caused by large GGCCTG repeat expansion in the NOP56 gene. The genetic diagnosis based on Southern blot is expensive and time-consuming. This study aimed to evaluate the reliability and effectiveness of whole exome sequencing (WES) for routine genetic diagnosis of suspected SCA36 patients. Methods: Pathogenic repeat expansions for SCAs including SCA36 were first analyzed based on WES data using ExpansionHunter in five probands from SCA families, then the results were confirmed by triplet repeat primed polymerase chain reaction (TP-PCR) and Southern blot. Results: GGCCTG repeat expansion in NOP56 was indicated in all five probands by WES, then it was found in 11 SCA patients and three asymptomatic individuals by TP-PCR. The sizes of GGCCTG repeat expansions were confirmed to be 1,390–1,556 by Southern blot. The mean age at onset of the patients was 51.0 ± 9.3 (ranging from 41 to 71), and they presented slowly progressive cerebellar ataxia, atrophy and fasciculation in tongue or limb muscles. Conclusion: The patients were clinically and genetically diagnosed as SCA36. This study proposed that WES could be a rapid, reliable, and cost-effective routine test for the preliminarily detection of SCA36 and other ataxia diseases. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia type 3 (SCA3) is a form of autosomal dominant cerebellar ataxia with a wide range of clinical manifestations, including ataxia and pyramidal and extrapyramidal signs. A few SCA3 patients have been noticed to be predisposed to the development of inclusion body myositis. It is still unknown whether muscle can be primarily involved in the pathogenesis of SCA3. This study reported an SCA3 family in which the index patient initially presented with parkinsonism, sensory ataxia, and distal myopathy but the absence of cerebellar and pyramidal symptoms. The clinical and electrophysiological studies implied a possible combination of distal myopathy and sensory–motor neuropathy or neuronopathy. MRI muscle showed selective fat infiltration and absence of denervated edema‐like changes, indicating the distal muscle weakness had a myopathic origin. Muscle pathology showed the myopathic involvement, besides neurogenic involvement, characterized by chronic myopathic changes with multiple autophagic vacuoles. Genetic screening revealed expanded CAG of 61 repeats in the ATXN3 gene, which showed co‐segregation in the family. Besides the neurogenic origin, the myopathic origin may be partly attributed to the limb weakness of SCA3 patients, which expands the spectrum of the clinical manifestation of SCA3. [ABSTRACT FROM AUTHOR]

Background and purpose: Neuronal intranuclear inclusion disease (NIID) is associated with CGG repeat expansion in the NOTCH2NLC gene. Although pure or dominant peripheral neuropathy has been described as a subtype of NIID in a few patients, most NIID patients predominantly show involvements of the central nervous system (CNS). It is necessary to further explore whether these patients have subclinical peripheral neuropathy. Methods: Twenty‐eight NIID patients, clinically characterized by CNS‐dominant involvements, were recruited from two tertiary hospitals. Standard nerve conduction studies were performed in all patients. Skin and sural nerve biopsies were performed in 28 and 15 patients, respectively. Repeat‐primed polymerase chain reaction and amplicon length polymerase chain reaction were used to screen the CGG repeat expansion in NOTCH2NLC. Results: All 28 patients can be diagnosed with NIID based on skin pathological and genetic changes. All patients predominantly showed CNS symptoms mainly characterized by episodic encephalopathy and cognitive impairments, but no clinical symptoms of peripheral neuropathy could be observed initially. Electrophysiological abnormalities were found in 96.4% (27/28) of these patients, indicating that subclinical peripheral neuropathy is common in NIID patients with CNS‐dominant type. Electrophysiological and neuropathological studies revealed that demyelinating degeneration was the main pathological pattern in these patients, although mild axonal degeneration was also observed in some patients. No significant association between CGG repeat size and the change of nerve conduction velocity was found in these patients. Conclusions: This study demonstrated that most patients with CNS‐dominant NIID had subclinical peripheral neuropathy. Electrophysiological examination should be the routinely diagnostic workflow for every NIID patient. [ABSTRACT FROM AUTHOR]

Objective: To describe clinical and genetic feature in a Chinese family with familial idiopathic basal ganglia calcification 3 (IBGC-3) caused by a novel mutation in the SLC20A2 gene., Methods: Clinical data was collected from a family with familial IBGC-3. All of the family members underwent cerebral CT. Potential mutation of the SLC20A2 gene were screened in the proband, 5 symptomatic patients, 5 asymptomatic family members, and 100 healthy Chinese controls. Exon 8 of the SLC20A2 gene was cloned into plasmid and sequenced., Results: There were 6 symptomatic patients (3 males and 3 females) in an autosomal dominant pedigree. The patients manifested as juvenile-onset paroxysmal kinesigenic dyskinesia, in addition to pyramidal signs in proband. 5 patients alive had calcification in bilateral basal ganglia and subcortical areas. One asymptomatic member also had calcification in the brain; and 2 cases of asymptomatic young members had bilateral globus pallidus calcification. A novel c.1086delC mutation in SLC20A2 gene has been identified in proband and 7 family members with intracranial calcification. The deletion mutation was not found in 2 family members without intracranial calcification and healthy controls members. There is no clear relationship between clinical symptoms and the severity of calcification in cerebral CT., Conclusion: Familial idiopathic basal ganglia calcification caused by the SLC20A2 gene mutation can manifest as juvenile onset paroxysmal kinesigenic dyskinesia. Further study should be done to validate the unrelated relationships between the severity of calcification in IBGC 3 cranial CT and clinical symptoms.

Background: To investigate the expression features of the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) in non-small cell lung cancer and its clinical significance., Methods: hnRNP A2/B1 expression of cancer tissues, paracancerous lung tissues, resected bronchial stump epithelium tissues was detected in 58 non-small cell lung cancer patients and pulmonary tissues in 30 patients with benigh pulmonary lesions as control by immunohistochemistry methods., Results: The positive expressive rate of hnRNP A2/B1 in lung cancer tissue (63.79%) was significantly higher than those in paracancerous lung tissue (43.10%) and benign pulmonary lesion tissues (20.00%) (P=0.000), and the positive rate in paracancerous lung tissue was also significantly higher than that in benign pulmonary lesion tissues (P < 0.05). The positive rate of hnRNP A2/B1 in the hyperplastic and dysplastic epithelium (40.00%) of resected bronchial stump was remarkably higher than that in normal bronchial epithelium (15.15%) in lung cancer patients (P=0.032). The positive rate of hnRNP A2/B1 in poor differentiated lung cancer (78.13%) was remarkably higher than that in moderate and well differentiated lung cancer (46.15%) (P < 0.05). The positive rate of hnRNP A2/B1 in lung cancer with lymph node metastasis (75.00%) was significantly higher than that without lymph node metastasis (50.00%) (P < 0.05). The positive rate of hnRNP A2/B1 in stage III+IV disease (78.57%) was significantly higher than that in stage I+II disease (50.00%) (P < 0.05). The positive rate of hnRNP A2/B1 in T3+T4 cancer (77.42%) was significantly higher than that in T1+T2 cancer (48.15%) (P < 0.05). The positive rate of hnRNP A2/B1 expression in lung cancer tissues was not related to histological classification of the cancer (P > 0.05)., Conclusions: The overexpression of hnRNP A2/B1 in cancer tissues may play an important role in the oncogenesis, development and metastasis of lung cancer. Detection of hnRNP A2/B1 expression may be helpful to diagnose lung cancer and to predict prognosis of the patients with lung cancer.