Objective:To explore the clinical, imaging, and genetic characteristics of an adult patient with sporadic Neuronal intranuclear inclusion disease (NIID).Methods:A patient who had visited the First People′s Hospital of Chenzhou on August 6, 2023 was selected as the study subject. Results of clinical examination, neuroimaging, and genetic testing were retrospectively analyzed along with a literature review. The number of GGC trinucleotide repeats in the 5′-untranslated region of the NOTCH2NLC gene was determined by GC-PCR. Results:The patient had presented with episodic encephalopathy, with enhanced magnetic resonance imaging showing enhancement features of the posterior cerebral cortex during the period of acute episode. Genetic testing revealed an increased number of GGC repeats ( n = 97) in the 5′- untranslated region of the NOTCH2NLC gene, which confirmed the diagnosis of NIID. Conclusion:Clinical attention should be paid to the enhanced MRI findings of patients with adult-onset NIID, for whom posterior cortical enhancement may be characteristic manifestation during the acute phase of encephalopathy-like episode.

Objective: As a gate-keeper enzyme link, pyruvate dehydrogenase E1 subunit alpha (PDHA1) functions as a key regulator during glycolysis and the mitochondrial citric acid cycle, which has been reported in several tumors. Nevertheless, the effects of PDHA1 on biological behaviors and metabolism remain unclear in cervical cancer (CC) cells. The study aims to explore the PDHA1 effects on glucose metabolism in CC cells and its possible mechanism. Methods: We first determined the expression levels of PDHA1 and activating protein 2 alpha (AP2α) as a PDHA1 potential transcription factor. The effects of PDHA1 in vivo were evaluated through a subcutaneous xenograft mouse model. Cell Counting Kit-8 assay, 5-ethynyl-2′-deoxyuridine (EdU) labeling assay, Transwell invasion assay, wound healing assay, Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and flow cytometry were performed in CC cells. Oxygen consumption rate (OCR) levels were determined to reflect aerobic glycolysis level in gastric cancer cells. Reactive oxygen species (ROS) level was measured with 2′, 7′-dichlorofluorescein diacetate kit. The relationship between PDHA1 and AP2α was examined by conducting chromatin immunoprecipitation assay and electrophoretic mobility shift assay. Results: In CC tissues and cell lines, PDHA1 was downregulated, while AP2α was upregulated. Overexpression of PDHA1 remarkedly inhibited the proliferation, invasion and migration of CC cells, and tumor growth in vivo, as well as promoted OCR, apoptosis and ROS production. Moreover, AP2α directly bound to PDHA1 within suppressor of cytokine signaling 3 promoter region to negatively regulate PDHA1 expression level. What is more, PDHA1 knockdown could effectively reversed the AP2α silencing-mediated suppressive effects on cell proliferation, invasion, migration, and the promotive effects of AP2α knockdown on OCR, apoptosis and ROS production. Conclusions Our findings demonstrate that AP2α negatively regulated PDHA1 via binding to PDHA1 gene promoter to promote malignant CC cell behaviors, which may provide a potential approach for CC therapeutics.

Objective:To analyze and compare the risk factors for hemorrhagic stroke and ischemic stroke and understand the exposure levels in population.Methods:A cohort study of risk factors of stroke was conducted in a rural community in Fengxian District of Shanghai in 2003, and the common risk factors of stroke were investigated at baseline survey, the cerebrovascular hemodynamics indexes were detected, the cerebrovascular function score was calculated according to the unified integral rule, and the incidence of stroke was observed in follow up. The risk factors for hemorrhagic stroke and ischemic stroke were analyzed by cohort study. The risk factors for two subtypes of stroke were compared.Result:A total of 10 565 participants were included in the study, with a mean follow-up period of (11.15±2.26) years, and 103 hemorrhagic stroke cases and 268 ischemic stroke cases were observed during follow-up period. The independent risk factors of hemorrhagic stroke included decreased cerebrovascular function score [hazard ratio ( HR)=1.56, 95% CI: 1.23-1.98], history of alcohol consumption ( HR=2.46, 95% CI: 1.39-4.34), hypertension ( HR=1.75, 95% CI: 1.00-3.07) and older age ( HR=1.07, 95% CI: 1.04-1.10). The independent risk factors of ischemic stroke included decreased cerebrovascular function score ( HR=1.43, 95% CI: 1.25-1.65), smoking history ( HR=1.52, 95% CI: 1.13-2.05), hypertension ( HR=1.51, 95% CI: 1.10-2.07), family history of stroke ( HR=1.89, 95% CI: 1.13-3.15), left ventricular hypertrophy ( HR=1.74, 95% CI: 1.07-2.81) and older age ( HR=1.07, 95% CI: 1.05-1.08). Conclusions:Decreased cerebrovascular function score, hypertension, and older age were common independent risk factors of both types of stroke, alcohol consumption history was an independent risk factor of hemorrhagic stroke, and smoking history, and family history of stroke and left ventricular hypertrophy were independent risk factors of ischemic stroke.

Perilla (Perilla frutescens L.) is an important edible-medicinal oil crop, with its seed containing 46%-58% oil. Of perilla seed oil, α-linolenic acid (C18:3) accounts for more than 60%. Lysophosphatidic acid acyltransferase (LPAT) is one of the key enzymes responsible for triacylglycerol assembly in plant seeds, controlling the metabolic flow from lysophosphatidic acid to phosphatidic acid. In this study, the LPAT2 gene from the developing seeds of perilla was cloned and designated as PfLPAT2. The expression profile of PfLPAT2 gene was examined in various tissues and different seed development stages of perilla (10, 20, 30, and 40 days after flowering, DAF) by quantitative real-time PCR (qRT-PCR). In order to detect the subcellular localization of PfLPAT2 protein, a fusion expression vector containing PfLPAT2 and GFP was constructed and transformed into Nicotiana benthamiana leaves by Agrobacterium-mediated infiltration. In order to explore the enzymatic activity and biological function of PfLPAT2 protein, an E. coli expression vector, a yeast expression vector and a constitutive plant overexpression vector were constructed and transformed into an E. coli mutant SM2-1, a wild-type Saccharomyces cerevisiae strain INVSc1, and a common tobacco (Nicotiana tabacum, variety: Sumsun NN, SNN), respectively. The results showed that the PfLPAT2 open reading frame (ORF) sequence was 1 155 bp in length, encoding 384 amino acid residues. Functional structure domain prediction showed that PfLPAT2 protein has a typical conserved domain of lysophosphatidic acid acyltransferase. qRT-PCR analysis indicated that PfLPAT2 gene was expressed in all tissues tested, with the peak level in seed of 20 DAF of perilla. Subcellular localization prediction showed that PfLPAT2 protein is localized in cytoplasm. Functional complementation assay of PfLPAT2 in E. coli LPAAT mutant (SM2-1) showed that PfLPAT2 could restore the lipid biosynthesis of SM2-1 cell membrane and possess LPAT enzyme activity. The total oil content in the PfLPAT2 transgenic yeast was significantly increased, and the content of each fatty acid component changed compared with that of the non-transgenic control strain. Particularly, oleic acid (C18:1) in the transgenic yeast significantly increased, indicating that PfLPAT2 has a higher substrate preference for C18:1. Importantly, total fatty acid content in the transgenic tobacco leaves increased by about 0.42 times compared to that of the controls, with the C18:1 content doubled. The increased total oil content and the altered fatty acid composition in transgenic tobacco lines demonstrated that the heterologous expression of PfLPAT2 could promote host oil biosynthesis and the accumulation of health-promoting fatty acids (C18:1 and C18:3). This study will provide a theoretical basis and genetic elements for in-depth analysis of the molecular regulation mechanism of perilla oil, especially the synthesis of unsaturated fatty acids, which is beneficial to the genetic improvement of oil quality of oil crops.
Acyltransferases ; Cloning, Molecular ; Escherichia coli/metabolism* ; Fatty Acids ; Perilla frutescens/metabolism* ; Plant Oils ; Plant Proteins/metabolism* ; Saccharomyces cerevisiae/metabolism* ; Seeds/chemistry* ; Tobacco/genetics*

Objective To evaluate the clinical efficacy and safety of simultaneous enhanced accelerated radiation therapy for brain metastases (SMART-Brain) combined with functional area protection. Methods SMART-Brain was planned for 60 patients with multiple brain metastases. Using the whole brain intensity modulation technique, important functional areas such as hippocampus were protected against irradiation by delivering a dose of 30 Gy in 10 fractions. Meanwhile, a high dose of 40 Gy was delivered to brain metastases in 10 fractions. All patients were followed up to evaluate the efficacy, incidence of adverse reactions, median overall survival (OS), and intracranial progression-free survival (IPFS). Results The effective rate was 73.33% (44 cases), the disease control rate was 91.67% (55 cases), median OS was 15.2 months, and IPFS was 12 months. The 1 and 2-year OS was 66.7% and 26.4%, and the 1-year IPFS was 46.7%. The MMSE scores at 1, 3, and 6 months after SMART showed no significant differences compared with baseline scores (P > 0.05). Grade 2 and above inner ear damage such as otitis media, hearing loss, and dizziness was absent. Conclusion Smart-Brain can significantly reduce the treatment time and better protect the organs at risk, and serves as an economical, safe, and effective radiotherapy regimen in areas with limited technical conditions.

Cellular mechanics, a major regulating factor of cellular architecture and biological functions, responds to intrinsic stresses and extrinsic forces exerted by other cells and the extracellular matrix in the microenvironment. Cellular mechanics also acts as a fundamental mediator in complicated immune responses, such as cell migration, immune cell activation, and pathogen clearance. The principle of atomic force microscopy (AFM) and its three running modes are introduced for the mechanical characterization of living cells. The peak force tapping mode provides the most delicate and desirable virtues to collect high-resolution images of morphology and force curves. For a concrete description of AFM capabilities, three AFM applications are discussed. These applications include the dynamic progress of a neutrophil-extracellular-trap release by neutrophils, the immunological functions of macrophages, and the membrane pore formation mediated by perforin, streptolysin O, gasdermin D, or membrane attack complex.
Microscopy, Atomic Force ; Neutrophils

Objective:To analyze the risk factors for protein-energy wasting(PEW)in elderly patients undergoing hemodialysis(HD)and peritoneal dialysis(PD), in order to provide evidence for the prevention of PEW and improve the prognosis in these patients.Methods:According to the diagnostic criteria for PEW proposed by the International Society for Renal Nutrition and Metabolism, 112 elderly patients who had undergone PD and HD without PEW from May 2016 to June 2020 in the renal medicine department of the Eighth People's Hospital of Shanghai, the geriatric medicine department of Zhongshan Hospital Affiliated to Fudan University and the renal medicine department of the Sixth People's Hospital Affiliated to Shanghai Jiaotong University were included as the non-PEW group.During the same period, 114 cases with PEW were recruited as the PEW group.Differences in general patient data, biochemical test values, anthropometric measurements, bioelectrical impedance and other index values were compared between the two groups.Independent risk factors for PEW in elderly HD and PD patients were analyzed by using binary Logistic regression analysis.Results:Compared with the non-PEW group, the PEW group had a higher mean age( t=0.951, P<0.001), a higher proportion of patients aged ≥65 years( χ2=17.161, P<0.001), a lower body mass index( t=6.740, P<0.001), a higher incidence of diabetic nephropathy( χ2=14.176, P<0.001), a higher hemodialysis rate( χ2=4.543, P=0.033), and a longer duration(months)of dialysis( t=2.306, P=0.023). Levels of serum transferrin, prealbumin, total protein, hemoglobin and total cholesterol and body cell mass index were lower( t=6.262, 13.405, 9.507, 8.341, 4.610, 5.599 and 2.499, all P<0.05), high-sensitivity C-reactive protein levels and the body water percentage were higher( t=6.380, 4.519, both P<0.001), and the upper arm muscle circumference was smaller( t=5.418, P=0.000)in the PEW group than in the non-PEW group.Binary Logistic regression analysis showed that age≥65 years, dialysis duration, serum albumin and high-sensitivity C-reactive protein levels were independent influencing factors for PEW in elderly HD patients( OR=2.762, 0.182, 2.694 and 2.980, P=0.023, 0.007, 0.009 and 0.027). Age ≥65 years, body mass index and the hemoglobin level were independent influencing factors for PEW in elderly PD patients( OR=2.452, 0.671 and 0.962, P=0.013, 0.000 and 0.000). Conclusions:The incidence of PEW is lower in elderly HD patients than in elderly PD patients.Clinical intervention should be carried out based on influencing factors, in order to prevent the occurrence of PEW.

Objective:To establish a 10-year comparison table of cerebrovascular function score and first stroke risk, and to provide a new method for screening of high-risk population of stroke.Methods:In the beginning of 2003, a cohort for studing stroke risk factors in those aged 40 years and over was established in a community of Shanghai by cluster sampling. The common risk factors of stroke were investigated with a unified questionnaire, and the cerebrovascular function (cerebral vascular hemodynamic indexes, CVHI) was measured. The baseline study was completed from April to June 2003 and December 2004 to January 2005, respectively. The incident of first stroke and all cause of death were followed up year by year. The follow-up period was up to December 31, 2014. The 10-year incidence of first stroke was calculated according to the baseline score of cerebrovascular function, and the score-risk control table was established to estimate 10-year first stroke risk in each score group. The role of cerebrovascular function score in stroke was also estimated.Results:The follow-up term of 10 565 participants was (10.26±2.00) years, and 350 patients had first stroke during the follow-up. The trend 10-year incidence of first stroke both in men and women was significantly increased with the decrease of the score of cerebrovascular function (trend χ2=296.125, P<0.01). As the 10-year risk of first stroke was higher than 5% and higher than 10%, the corresponding CVHI score was lower than 70 and 40 points in males and lower than 30 and 20 points in females. When the scores of cerebral vascular function were divided by every 25 points, incidence of first stroke in each group from top to bottom was 1.9%, 4.7%, 10.8%, 15.2% in males and 1.6%, 4.4%, 4.8%, 11.4% in females, respectively. As compared to the top, the relative risk (95% CI) of first stroke in the lower groups was 2.61(1.67-4.07), 6.46(4.22-9.89), 9.74(6.53-14.52) for males and 2.82(1.93-4.12), 3.15(1.99-4.99), 8.12(5.65-11.68) for females, respectively. Multivariate analysis showed that the factors being selected into the regression equation were cerebrovascular function score, age, hypertension history, stroke family history and smoking history, among which the role of cerebrovascular function score was the strongest. Conclusion:The risk of first stroke increases significantly with the decrease of cerebrovascular function score, which can be used to assess the 10-year risk of first stroke.

Objective To compare the dosimetric characteristics of non-coplanar and coplanar field technology in static intensity-modulated radiotherapy of gastric cancer patients, so as to provide a reference for clinical radiotherapy plan selection. Methods Thirty-six patients with gastric cancer were selected to receive intensity-modulated radiotherapy in Huanggang Central Hospital, which was designed plan A and B. Group A used 7-field coplanar technology, while Group B used 7-field non-coplanar technology. We compared the differences of the optimized monitor unit, the dosimetry of organs at risk and target areas between group A and group B. Results Both group A and B could meet the requirements of doctors. The homogeneity index (0.14 ± 0.02), the conformity index (0.98 ± 0.01), D_min (4315.21 ± 16.74) cGy、D_mean (4679.28 ± 28.39) cGy and D_max(4952.30 ± 33.26) cGy of target areas in group B were better than those of group A. Moreover, the monitor unit of group B was much lower than that of group A, and the difference was statistically significant (P < 0.05). The D_max, D_mean, V₁₅, V₂₀ and V₃₀ of the left and right kidneys in group B were lower than those of group A. The D_max (3408.57 ± 46.03) cGy, D_mean (1250.32 ± 14.27) cGy and V₂₀ (44.91% ± 6.67%) of spinal cord and the D_max (3408.57 ± 46.03) cGy, D_mean (1720.55 ± 17.42) cGy, V₂₀ (25.31% ± 7.78%) and V₃₀ (18.52% ± 1.56%) of small intestine were also lower than those of group A. The differences were statistically significant (P < 0.05). Conclusion The non-coplanar field radiation plan has more advantages in terms of target dose distribution and protection of organs so that it can be more considerably used in the process of planning and design.

The high rotational speed of the axial flow blood pump and flow separation of the centrifugal blood pump are the main causes for blood damage in blood pump. The mixed flow blood pump can effectively alleviate the high rotational speed and the flow separation. Based on this, the purpose of this study is to explore the performance of the mixed blood pump with a closed impeller. A mixed flow blood pump with closed impeller was studied by numerical simulation in this paper. The flow field characteristics and the pressure distribution of this type of blood pump were analyzed. The hydraulic performance of the blood pump and the possible damages to red blood cells were also discussed. At last, pump performance was compared with the mixed flow blood pump with semi-open impeller. The results show that the mixed flow blood pump with close impeller studied in this paper can operate safely and efficiently with a good performance. The pump can reach the pressure head of 100 mmHg at 5 L/min mass flow rate. Flow in the blood pump is uniform and no obvious separation or vortex occurs. Pressure distribution in and on the impeller is uniform and reasonable, which can effectively avoid the thrombosis of blood. The average mean value of hemolysis index is 4.99 × 10 . The pump has a good biocompatibility. Compared with the mixed flow blood pump with semi-open impeller, the mixed flow blood pump with closed impeller has higher head and efficiency, a smaller mean value of hemolysis index prediction, a better hydraulic performance and the ability to avoid blood damage. The results of this study may provide a basis for the performance evaluation of the closed impeller mixed flow blood pump.
Computer Simulation ; Equipment Design ; Heart-Assist Devices ; Hemolysis ; Humans ; Thrombosis ; prevention & control