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Writer's cramp (WC) dystonia is a rare disease that causes abnormal postures during the writing task. Successful research studies for WC and other forms of dystonia are contingent on identifying sensitive and specific measures that relate to the clinical syndrome and achieve a realistic sample size to power research studies for a rare disease. Although prior studies have used writing kinematics, their diagnostic performance remains unclear.This study aimed to evaluate the diagnostic performance of automated measures that distinguish subjects with WC from healthy volunteers.A total of 21 subjects with WC and 22 healthy volunteers performed a sentence-copying assessment on a digital tablet using kinematic and hand recognition softwares. The sensitivity and specificity of automated measures were calculated using a logistic regression model. Power analysis was performed for two clinical research designs using these measures. The test and retest reliability of select automated measures was compared across repeat sentence-copying assessments. Lastly, a correlational analysis with subject- and clinician-rated outcomes was performed to understand the clinical meaning of automated measures.Of the 23 measures analyzed, the measures of word legibility and peak accelerations distinguished subjects with WC from healthy volunteers with high sensitivity and specificity and demonstrated smaller sample sizes suitable for rare disease studies, and the kinematic measures showed high reliability across repeat visits, while both word legibility and peak accelerations measures showed significant correlations with the subject- and clinician-rated outcomes.Novel automated measures that capture key aspects of the disease and are suitable for use in clinical research studies of WC dystonia were identified. © 2022 International Parkinson and Movement Disorder Society.

Lihua Han,1 En-Hua Wang,2 Liang Wang2 1The Central Laboratory of Morphology, Shenyang Medical College, Shenyang, People’s Republic of China; 2Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Lihua Han, The Central Laboratory of Morphology, Shenyang Medical College, Shenyang, People’s Republic of China, Email hanlihualn@163.comAbstract: Undifferentiated large cell carcinoma of the thymus with a Castleman disease (CD)-like reaction is a thymic carcinoma accompanied by an inflammatory reaction closely resembling the morphological features of CD. This disease is extremely rare and distinctive, only five cases have been documented in a single report, and all five cases were associated with a reaction like the hyaline vascular type CD. For the first time, we report two cases of undifferentiated large cell carcinoma of the thymus with a plasma cell type CD-like reaction. The two cases presented similar histological findings and immunoprofiles. Undifferentiated large cells were arranged in nests and cords within hyperplastic follicles, mimicking pseudogerminal centers. Abundant plasma cells were distributed in the interfollicular areas. The tumor cells were positive for CK-pan and BRG1 staining but negative for CD5, CD117, CK5/6, p63, p40, and EBER. Therefore, the diagnoses of squamous cell carcinoma, lymphoepithelial carcinoma, or micronodular thymic carcinoma with lymphoid hyperplasia were excluded. Even though the carcinoma cells showed high-grade nuclear pleomorphism with prominent nucleoli, these two cases presented indolent clinical courses, which were consistent with the previous report.Keywords: Castleman disease-like reaction, immunohistochemistry, prognosis, thymic carcinoma, undifferentiated large cell carcinoma

Clear cell sarcoma of soft tissue (CCSST) is a rare malignant tumor occurring in the extremities of young adults. The tumor cells arranged in nests and sheets, with clear to eosinophilic cytoplasm separated by fibrous septa. CCSST has been documented to have atypical histopathological features, such as epidermotropism or myxoid differentiation, which may set pitfalls in differential diagnosis. Herein, we report a case of CCSST with purely plasmacytoid morphology which has never been described. The patient, a 15-year-old male, presented with a 5-cm mass in his left inguinal area. He received cryotherapy for a “black mole” on his back two years ago without pathology record. Positron emission tomography-computed tomography examination showed nodules in the left groin and the lung, the latter was considered as metastasis. Needle biopsy of inguinal mass showed tumor cells were uniformly sized, with eosinophilic cytoplasm and eccentric, basophilic nuclei, resembling plasmocytes. Immunostaining showed strong expression of S-100, HMB45, Melan-A, and MUM-1 in all tumor cells, while CD79a and CD38 were negative. Genetic analysis revealed the tumor harboring no BRAF mutations but EWSR1 rearrangement. Accordingly, the diagnosis of CCSST with plasmacytoid morphology was made. This is the first case of CCSST with purely plasmacytoid morphology which should be aware during evaluating and differentiating CCSST from tumors with similar morphology, such as plasmacytoid melanoma and extramedullary plasmacytoma, etc.

Clear cell sarcoma of soft tissue (CCSST) is a rare malignant tumor that occurs in the extremities of young adults. CCSST has been documented to have atypical histopathological features, such as epidermotropism or myxoid differentiation, which may set pitfalls in the differential diagnosis. We report a case of CCSST with plasmacytoid morphology which has never been described.A 15-year-old male, presented with a 5-cm mass in his left inguinal area.Positron emission tomography-computed tomography examination showed nodules in the left groin and the lung, the latter was considered metastasis. A core needle biopsy with the diagnosis of CCSST with plasmacytoid morphology was made according to histology, immunostaining, and molecular analysis.The patient received chemotherapy of doxorubicin and ifosfamide.The patient failed to respond to the standard chemotherapy and deceased twelve months after diagnosis.This special case of CCSST with plasmacytoid features demonstrated a morphological variation never been documented and may easily lead to misdiagnosis. For such cases, molecular analysis is essential to provide solid evidence for accurate diagnosis.

Our previous studies indicate that resistance induction using first-generation tyrosine kinase inhibitors (TKIs) in lung cancer is accompanied with p120-catenin (p120ctn) cytoplasmic translocation from the membrane. However, the molecular mechanism underlying p120ctn intracytoplasmic translocation has not yet been reported. We performed immunohistochemistry to detect the correlation of p120ctn distribution with protein tyrosine phosphatase non-receptor type 12 (PTP-PEST) and p120ctn Y335 phosphorylation levels in non-small cell lung cancer (NSCLC) patients. After resistance induction using first-generation TKIs in lung cancer cells, Western blotting and substrate trapping were used to assess PTP-PEST expression and its influence on p120ctn Y335 phosphorylation, as well as the role of p120ctn Y335 phosphorylation on the association of p120ctn with E-cadherin and p120ctn membrane/cytoplasm translocation. In 197 samples collected from NSCLC patients, cytoplasmic p120ctn and enhanced p120ctn Y335 phosphorylation were associated with decreased PTP-PEST. After resistance induction using gefitinib, decreased PTP-PEST expression was accompanied by enhanced phosphorylation of p120ctn Y335 and p120ctn translocated to the cytoplasm. In gefitinib-resistant cells, PTP-PEST overexpression restrained p120ctn Y335 phosphorylation and restored membrane p120ctn expression. PTP-PEST enhanced the interaction of p120ctn with E-cadherin and elevated p120ctn membrane expression. However, increased p120ctn-Y335F mutant had no effect on p120ctn interaction with E-cadherin and membrane/cytoplasm translocation compared with the control group. In conclusion, resistance to first-generation TKIs inhibited PTP-PEST expression, which promoted p120ctn-Y335 phosphorylation and reduced the interaction of p120ctn with E-cadherin, resulting in p120ctn cytoplasmic translocation.

Background: SIPA1L3 is a member of the signal-induced proliferation-associated (SIPA) protein family, only limited data about the SIPA1L3 are currently available in human carcinoma. Our present study provides the expression pattern and function of SIPA1L3 in non-small cell lung cancer (NSCLC).Methods: We performed immunohistochemistry to detect the distribution of SIPA1L3 in NSCLC specimens and analyzed the relationship between SIPA1L3 expression and patients clinicopathological feature. We used small interfering RNA (siRNA) to specifically silence SIPA1L3, then investigated its effect on cell growth and invasion in human lung cancer cell lines. Western blot and immunoprecipitation were performed to show the interaction of SIPA1L3 with the core proteins of Hippo pathway, and the Hippo pathway activity.Results: Immunohistochemical staining showed that SIPA1L3 was cytoplasmic increasing in 147 of 217 cases. High levels of SIPA1L3 expression were associated with poor differentiation and a high tumor node metastasis stage, positive lymph nodal status, and poor prognosis. Downregulation of SIPA1L3 inhibited cell EMT, growth, and invasion. As well as SIPA1L3 inhibited Hippo pathway. SIPA1L3 interacted with AMOT, which inhibited AMOT binding to Pals, then decreased nuclear location of YAP.Conclusions: SIPA1L3 overexpression may be a marker for advanced NSCLC. SIPA1L3 reduction inhibits the proliferative and invasive ability of the lung cancer cells, which involves the Hippo pathway by contacting with AMOT.

Transcription factor E3 (TFE3) is a useful marker for tumors with Xp11.2 translocation, including alveolar soft part sarcoma and renal cell carcinoma. Recently, TFE3 overexpression was also found in granular cell tumors (GrCTs). However, the case cohorts of these two studies were limited to only 11 and 6 cases. Whether aberrant TFE3 expression is a common feature of Asian patients with GrCT requires further investigation. In the present study, immunohistochemical staining and TFE3 break-apart fluorescence in situ hybridization (FISH) assay were performed in 45 samples of GrCTs obtained from Chinese patients recruited from three medical centers in northeast China. Diffusive and marked nuclear staining for TFE3 was identified in 11/45 (24%) cases, which was lower than previously reported. Focal or weak TFE3 staining was identified in 13/45 (29%) cases. The remaining 21 cases were negative stained. In addition, GrCTs in subcutaneous tissue exhibited a relatively higher ratio (8/45, 18%) for TFE3 expression, compared with those in other sites. Furthermore, according to FISH data, no rearrangement or amplification of TFE3 was identified in these cases, whether they were positively or negatively stained for TFE3. The results from the present study demonstrated that part of patients GrCTs exhibited TFE3 overexpression, which suggested that this may not be derived from gene rearrangement.

Cytokine-induced killer (CIK) cells represent a heterogeneous cell population, including a large majority of CD3+CD56+ cells, a relatively minor fractions of typical T cells (CD3+CD56-), and natural killer (NK) cells (CD3-CD56+). In order to elucidate the tumor killing mechanism of these three subpopulations of CIK cells, this review summarized the concordances and differences among CD3+CD56+ CIK cells, CD3-CD56+ NK cells and CD3+CD56- T cells to the following aspects: the effects of cell surface molecules, mechanisms of tumor killing, and clinical applications of these cells in immunotherapy. NK cells can be classified into CD56brightCD16- NK cells, which produce cytokines in response to monokine co-stimulation, and the CD56dimCD16+ NK cells, which contribute to lysing susceptible target. Also, the immunity of NK cells is mainly regulated by several immune-receptors, such as ACR, ICR, NCR and KIRs. T cells require TCR and co-stimulatory molecules for initiation of T cell activation. The CD3+CD56+ CIK cells co-express with T-cell marker CD3 and NK cell marker CD56 to appear the most potent cytotoxicity and high impact on adoptive cellular immunotherapy. These CIK subpopulations share some similar tumor killing mechanisms. LFA-1 not only mediates the binding of NK cells to target cells through its ligand ICAM-1 to localize actin accumulation but also acts as a co-stimulatory receptor on NK cells. LFA-1 also functions as co-stimulatory receptor for T cells to transmit intracellular signals from the TCR to LFA-1. Furthermore, cytotoxic effect of CD3+CD56+ CIK cells is blocked by antibodies directly against LFA-1 and its counter receptor, ICAM-1. Clinically, antibody-dependent cell-mediated cytotoxicity (ADCC) is shown in both NK cells and T cells for tumor killing while dendritic cells are another main regulator for the activation of three subpopulations. In summary, CD3+CD56+ CIK cells have dual-functional capability as T-cell subsets which acquire NK cells function and reserve TCR-mediated specific cytotoxicity. Meanwhile, CIK cells play important roles in tumor immunology. It paves the way to more effective immunotherapies for various tumors.

Discrete element software is used to simulate the excavation of a rock slope in Puli-Xuanwei Expressway in Yunnan Province. Through monitoring displacement development characteristics in different positions of slope, the result shows that the minimum horizontal displacement under excavation exists in the top of the slope, meanwhile the maximum horizontal displacement occurs in the foot and waist of the slope, and the maximum vertical displacement occurs in the top of the slope. Comparing rock slope in such conditions as different stratum angles, directions, rock characteristics and thickness, it concludes possible failure modes of slope and the variation law of safety coefficient under different conditions. This paper is instructive and offers reference for the practical engineering.

Through experiment, the variation of the exhaust energy of the vehicle diesel engine is studied, a set of vehicle diesel engine-organic Rankine cycle (ORC) combined system with internal heat exchanger (IHE) is designed, the zeotropic mixtures R416A is used as the working fluids for the ORC system with IHE, by theoretical analysis and numerical calculation, the variation of the vehicle diesel engine-ORC combined system with IHE under entire operating conditions of the diesel engine is studied, the calculation results show that, when engine is operating at high speed and high torque, the performance of the vehicle diesel engine-ORC combined system with IHE is higher.

Objective: To study the lobular pheasant tail leaf volatile chemical composition. Methods: the extraction of volatile chemical composition lobular pheasant tail blades of steam distillation, gas chromatography - mass spectrometry method for the separation and identification of its composition and relative content. Results and conclusion: 41 chemical compounds were identified. The main chemical constituents of volatile oil seeTable 1.

The evaporator is a critical component when using organic Rankine cycle (ORC) to recover waste heat from an internal combustion engine. Evaluating the amount of heat quantity that can be transferred in a designed evaporator is very important for a successful ORC system. In this paper, a finned tube evaporator used for recovering the exhaust waste heat of a diesel engine was presented. The mathematical model for the evaporator was set up according to the dimensions of the designed evaporator along with the specified working conditions of ORC. The evaporator performance was analyzed as the matched diesel engine operating at the rated power point. The results indicate that the heat transfer quantity of the designed evaporator can be reached at 76 kW, and the exhaust temperature at the evaporator exit can be reduced to 115°C.

Human telomerase reverse transcriptase (hTERT) gene amplification was detected in pleural effusions of patients with lung cancer (n = 69) and in patients with benign lung disease (n = 46) when using a quantitative polymerase chain reaction (qPCR) technique.hTERT gene relative copy numbers were significantly higher in effusions from patients with malignant, adenocarcinoma and small-cell lung cancer than in effusions from patients with benign lung disease (P.01). By using a threshold value of 1.39, hTERT gene amplification was significantly more frequent in malignant effusions compared with benign effusions and more likely to be positive for malignant effusions, compared with cytology (P.01). The diagnostic performance of qPCR of hTERT gene amplification was significantly higher than that of cytology, in terms of sensitivity (91.3% vs. 56.5%), negative predictive value (87.8% vs. 60.5%), and accuracy (92.2% vs. 73.9%).Detecting hTERT gene amplification by qPCR appears suitable for distinguishing carcinoma cells from reactive mesothelial cells in pleural effusions. hTERT gene amplification was more sensitive than cytology and may be useful for diagnosing pleural micrometastases.

The aim of the present study was to determine whether the size of the zona pellucida (ZP) thinning area by laser-assisted hatching affected the potential development of vitrified-warmed embryos. A total of 196 vitrified-warmed cleavage-stage embryos (from 49 patients, four sister embryos per patient) were used in the study, i.e., four sister embryos from each patient were randomly assigned to four groups: a control group of embryos that were not zona-manipulated (zona intact, group A); one experimental group of embryos in which a quarter of the zona pellucida was thinned using laser-assisted ZP thinning (group B); a second experimental group of embryos in which half of ZP was thinned (group C); and a third group in which two-thirds of the ZP was thinned (group D). Subsequent blastocyst development was assessed. Microscopy was performed to study the hatching process of the embryos after zona thinning. The blastocyst formation rates were 71.43% in group A, 67.35% in group B, 65.31% in group C, and 51.02% in group D (groups B-D vs. group A, P=0.661, P=0.515, P=0.038, respectively). The rates of complete hatching were 30.61% in group A, 38.78% in group B, 61.22% in group C, and 48.98% in group D (groups B-D vs. group A, P=0.396, P=0.002, P=0.063, respectively). For a subgroup of patients, there was a significant difference in the complete hatching in all the groups for women aged

Objective. To evaluate diagnostic utility of Dishevelled-3 (DVL-3) mRNA andδ-catenin mRNA expression in pleural effusions of patients with lung cancer.Methods. DVL-3 mRNA andδ-catenin mRNA levels were assessed by performing RT-PCR on pleural effusion specimens from patients with lung cancer (n=75) and with lung benign disease (n=51).Results. The expressions of DVL-3 mRNA andδ-catenin mRNA were significantly higher in malignant than in benign lung disease (P<0.01) and were obviously higher than cytology in adenocarcinoma (P<0.01). In single use, DVL-3 mRNA had the highest specificity (94.1%) and PPV (95.7%), whereasδ-catenin mRNA had the highest sensitivity (92.0%) and NPV (88.5%). When combinations of markers were evaluated together, DVL-3 mRNA andδ-catenin mRNA gave a high-diagnostic performance: sensitivity of 100.0%, NPV of 100.0%, and accuracy of 96.0%, respectively.Conclusion. As molecular markers of detecting pleural micrometastasis, DVL-3 mRNA andδ-catenin mRNA are helpful to diagnose the cancer cells in pleural effusions of patients with lung cancer.

Energy saving and environment protection are two important issues that today’s automobile industry must emphasize. Lots of heat energy waste with the exhaust gas when the engine is running. If this part of waste heat can be recovered, the energy efficiency will be improved. Thus plenty of energy can be saved and the global warming also can be reduced. In this paper, the organic Rankine cycle whose working fluid was R245fa was studied. It was adopted to recover the gasoline engine waste heat. The mathematical model of the organic Rankine cycle was built up in Matlab to search the optimized working condition. The pinch analysis method was used to analyze the outlet temperature of the exhaust gas. The results indicate that organic Rankine cycle is a good way to recover the gasoline engine waste heat, especially in the high load conditions. The temperature of the exhaust gas can be apparently decreased.

Between May 2008 and October 2009, a total of 2103 interns were randomly tested for nasal colonization of S. aureus and methicillin-resistant Staphylococcus aureus (MRSA). The prevalence of S. aureus among staphylococci specimens was 23.1%, and among the total S. aureus the MRSA prevalence was 9.4%. MRSA isolates were further subtyped using genetic element staphylococcal cassette chromosome mec (SCCmec) typing, pulsed-field gel electrophoresis (PFGE) band pattern, and multilocus sequence typing. SCCmec type IVa was the most prevalent strain, at 45.4 %. Eleven PFGE patterns were identified in MRSA strains, with 1 predominant (pulsotype A, 45.5%). Eight strains which belonged to clonal complex 78 carried type IVa SCCmec and produced type 3 coagulase. Panton-Valentine leukocidin (PVL) genes (lukS and F-PV) were identified in 10 (45.4%) MRSA strains; these predominately carried ϕSa2958type and ϕSa108PVL-like type PVL phages. After inducing prophages, 8 strains infected other S. aureus isolates and could generate novel PVL-positive strains of S. aureus. The present study demonstrates that interns can carry certain MRSA strains asymptomatically and contribute to the spread of MRSA between the community and hospital.

Protein kinase B (PKB, also called Akt) is known as a serine/threonine protein kinase. Some studies indicate that the Akt signalling pathway strongly promotes G2/M transition in mammalian cell cycle progression, but the mechanism remains to be clarified, especially in the fertilized mouse egg. Here, we report that the expression of Akt at both the protein and mRNA level was highest in G2 phase, accompanied by a peak of Akt activity. In addition, the subcellular localization of p21(Cip1/WAF1) has been proposed to be critical in the cell cycle. Hence, we detected the expression and localization of p21(Cip1/WAF1) after injecting fertilized mouse eggs with Akt mRNA. In one-cell stage fertilized embryos microinjected with mRNA coding for a constitutively active myristoylated Akt (myr-Akt), p21(Cip1/WAF1) was retained in the cytoplasm. Microinjection of mRNA of kinase-deficient Akt(Akt-KD) resulted in nuclear localization of p21(Cip1/WAF1) . Meanwhile, microinjection of different types of Akt mRNA affected the phosphorylation status of p21(Cip1/WAF1) . However, there was no obvious difference in the protein expression of p21(Cip1/WAF1) . Therefore, Akt controls the cell cycle by changing the subcellular localization of p21(Cip1/WAF1) , most likely by affecting the phosphorylation status of p21(Cip1/WAF1) .

Variable Nozzle Turbocharger (VNT) was invented to solve the problem of matching an ordinary turbocharger with an engine. VNT can harness exhaust energy more efficiently, enhance intake airflow response and reduce engine emissions, especially during transient operating conditions. The difficulty of VNT control lies in how to regulate the position of the nozzle at different engine working conditions. The control strategy designed in this study is a combination of a closed-loop feedback controller and an open-loop feed-forward controller. The gain-scheduled proportional-integral-derivative (PID) controller was implemented as the feedback controller to overcome the nonlinear characteristic. As it is difficult to tune the parameters of the gain-scheduled PID controller on an engine test bench, system identification was used to identify the plant model properties at different working points for a WP10 diesel engine on the test bench. The PID controller parameters were calculated based on the identified first-order-plus-dead-time (FOPDT) plant model. The joint simulation of the controller and the plant model was performed in Matlab/Simulink. The time-domain and frequency-domain performances of the entire system were evaluated. The designed VNT control system was verified with engine tests. The results indicated that the real boosting pressure traced the target boosting pressure well at different working conditions.

It is well documented that protein kinase A (PKA) acts as a negative regulator of M phase promoting factor (MPF) by phosphorylating cell division cycle 25 homolog B (Cdc25B) in mammals. However, the molecular mechanism remains unclear. In this study, we identified PKA phosphorylation sites in vitro by LC-MS/MS analysis, including Ser(149), Ser(229), and Ser(321) of Cdc25B, and explored the role of Ser(149) in G(2)/M transition of fertilized mouse eggs. The results showed that the overexpressed Cdc25B-S149A mutant initiated efficient MPF activation by direct dephosphorylation of Cdc2-Tyr(15), resulting in triggering mitosis prior to Cdc25B-WT. Conversely, overexpression of the phosphomimic Cdc25B-S149D mutant showed no significant difference in comparison with the control groups. Furthermore, we found that Cdc25B-Ser(149) was phosphorylated at G(1) and S phases, whereas dephosphorylated at G(2) and M phases, and the phosphorylation of Cdc25B-Ser(149) was modulated by PKA in vivo. In addition, we examined endogenous and exogenous Cdc25B, which were expressed mostly in the cytoplasm at the G(1) and S phases and translocated to the nucleus at the G(2) phase. Collectively, our findings provide evidence that Ser(149) may be another potential PKA phosphorylation target of Cdc25B in G(2)/M transition of fertilized mouse eggs and Cdc25B as a direct downstream substrate of PKA in mammals, which plays important roles in the regulation of early development of mouse embryos.

Energy saving and environment protection are two most important issues that today’s internal combustion engine industry must tackle with. Lots of heat energy waste with the exhaust gas when the engine is running. Organic Rankine cycle (ORC) is a good method to recover the waste heat of the engine exhaust. In this paper, the mathematical model of ORC was built up in Matlab and the parameters were optimized using genetic algorithm (GA). Eight pure component organic working fluids were selected and compared. The results indicate that the evaporating pressure of the working fluid and the condensing temperature are two important parameters for ORC; the super heater also can enhance the system thermal efficiency slightly.