[Expression of programmed cell death ligand 1 and clinicopathological and immunological characteristics in fumarate hydratase-deficient renal cell carcinoma].

Objective: To investigate the expression of programmed cell death ligand 1 (PD-L1), clinicopathologic features, immunohistochemical expression and molecular characteristics in fumarate hydratase (FH)-deficient renal cell carcinoma and to explore the potential application of immunotherapy in the patients. Methods: There were six patients with FH-deficient renal cell carcinoma treated at the First Affiliated Hospital of Fujian Medical University between January 2020 and October 2022. The clinical data, histological morphology, immunophenotype, PD-L1 expression and next-generation sequencing results were tabulated and analyzed. Results: There were 6 patients, all male, age ranged from 37 to 72 years (mean 45.7 years). Four cases were high-grade (WHO/ISUP grade3-4) with 2 or more histologic patterns, including papillary (most common), glandular, tubular, vesicular, ethmoid, nest-like, cystic and solid structures. Two cases were low-grade which showed nest-like, glandular, or tubular arrangement with eosinophilic flocculent cytoplasm and small intracellular vacuoles. Immunohistochemical analysis revealed strong expression of 2SC in all 6 cases, negative expression of FH in 5 cases, and positive expression of GATA3 in 5 cases. In high-grade cases, the mean values of CD4 and CD8 positive T-lymphocytes in advanced tumor invasion were 180.3/mm2 and 130.5/mm2, respectively. PD-L1 combined positive scores (CPS) were 20, 50, 5 and 30, respectively. The Ki-67 proliferative index were 20%, 20%, 10% and 30%, respectively. In low-grade cases, the mean values of CD4 and CD8 positive T-lymphocytes were 123.0/mm2 and 100.5/mm2, respectively. The PD-L1 CPS score was 1, and the Ki-67 proliferation index was 3%. High-throughput sequencing showed FH gene somatic mutation in 3 cases, FH gene germline mutation in 2 cases, and FH gene mutation was not detected in one case. Conclusion: FH-deficient renal cell carcinoma is more commonly high-grade than low grade. FH and 2SC are immunohistochemical markers used in the diagnosis of FH-deficient renal cell carcinoma, and GATA3 positivity is supportive of the diagnosis. The tumor infiltration of high-grade FH-deficient renal cell carcinoma shows an increase in CD4 and CD8 positive T-lymphocytes, and high expression of PD-L1; thus, anti-PD-L1 immunotherapy can be used as a treatment option.

First Report of Tomato mottle mosaic virus infecting Chinese snake gourd (Trichosanthes kirilowii) in China.

Tomato mottled mosaic virus (ToMMV) was first identified in tomato in Mexico (Li et al. 2013). It belongs to the genus Tobamovirus and family Virgaviridae, and is a positive-sense single-stranded RNA virus. The viral genome contains about 6400 nucleotides, encoding four proteins, including the 126 K protein, 183 K protein, movement protein (MP) and coat protein (CP) (Tu et al. 2021). ToMMV mainly poses a serious risk to solanaceous crops. The virus-infected plants appear stunted growth and top necrosis, and the disease leaves show mottled, shrinkage and necrosis symptoms, resulting in a significant decline in tomato fruit yield and quality (Li et al. 2017; Tu et al. 2021). Chinese snake gourd (Trichosanthes kirilowii Maxim) is a perennial climbing herb in the family Cucurbitaceae, and the fruit, seed, peel and root can all be used as traditional Chinese medicine. In May of 2021, twenty-seven symptomless seedlings (developed from tissue culture plantlets) were randomly collected from nursery in Fengyang, Anhui Province. Total RNA of each sample was extracted, and RT-PCR was performed using degenerate tobamovirus primers Tob-Uni1 (5'-ATTTAAGTGGASGGAAAAVCACT-3') and Tob-Uni2 (5'-GTYGTT GATGAGTTCRTGGA-3') (Letschert et al. 2002). Amplicons with expected size were obtained from 6 of 27 samples and sequenced. Alignment results showed that the nucleotide sequence identities ranged from 98.7 to 100% with all ToMMV isolates deposited in NCBI GenBank. Then, ToMMV coat protein (CP) gene was amplified using specific primers CP-F (5'-ATGTCTTACGCTATTACTT CTCCG-3') and CP-R (5'-TTAGGACGCTGGCGCAGAAG-3'). The CP fragment was obtained and sequenced. Sequence alignment indicated that CP sequence of isolate FY (GenBank accession no. ON924176) exhibited a 100% identity with ToMMV isolate LN (MN853592.1). The anti-ToMMV polyclonal antibody (PAb) was prepared by the author (S.L.) by immunizing rabbit with purified virus from Nicotiana benthamiana, and serological tests (dot-enzyme linked immunosorbent assay, Dot-ELISA) of RNA-positive T. kirilowii leaf samples using anti-ToMMV PAb were also positive. To fulfill a Koch's postulate, a pure culture of ToMMV was obtained from N. benthamiana using infectious cDNA clone of ToMMV (Tu et al. 2021), and then healthy T. kirilowii plants were mechanically inoculated with a prepared inoculum from ToMMV-infected N. benthamiana, as described previously (Sui et al. 2017). T. kirilowii seedlings showed chlorosis and leaf tip necrosis symptoms at 10 and 20 day post-inoculation respectively, and ToMMV infection on symptomatic plants was also verified by RT-PCR detection using primers CP-F and CP-R. These results demonstrated that T. kirilowii is a host of ToMMV under natural conditions, which might threaten the production of this medicinal plant. The seedlings from nursery appeared to be asymptomatic, but the plants showed chlorosis and necrosis symptoms after indoor inoculation. In qRT-PCR analysis, viral accumulation level in greenhouse-inoculated plants was a 25.6-fold of that in field-collected samples, which may be the reason of different symptom expression between field samples and inoculated samples. ToMMV has now been detected from the solanaceous (tomato, pepper and eggplant) and leguminous (pea) crops in the field (Li et al. 2014; Ambrós et al. 2017; Zhang et al. 2022). To our knowledge, this is the first report of natural infection of ToMMV in T. kirilowii as well as its natural infection on Cucurbitaceae plants.

Transcatheter valve repair of tricuspid regurgitation with the PASCAL system: TriCLASP study 30-day results.

BACKGROUND: Severe tricuspid regurgitation (TR) is independently associated with increased morbidity and mortality. Percutaneous transcatheter approaches may offer an alternative for patients not amenable to surgery. METHODS: TriCLASP is a prospective, single-arm, multicenter European post-market clinical follow-up study (NCT04614402) to evaluate the safety and performance of the PASCAL system (Edwards Lifesciences) in patients with severe or greater TR. At 30 days, a composite of major adverse events (MAEs) adjudicated by a clinical events committee, echocardiographic parameters adjudicated by core laboratory, and clinical, functional, and quality-of-life measures were evaluated. RESULTS: Mean age of the 74 enrolled patients was 80.3 years, with 58.1% female, 90.5% systemic hypertension, and 77.0% in New York Heart Association (NYHA) class III/IV. Mean Society for Thoracic Surgeons score (MV repair) was 9.0%. TR severity was significantly reduced at discharge (p < 0.001) and sustained at 30 days (p < 0.001), and 90.0% of patients achieved ≤moderate TR. The composite MAE rate at 30 days was 3.0%, including 4 events in 2 patients: cardiovascular mortality 1.5%, stroke 1.5%, renal complications requiring unplanned dialysis or renal replacement therapy 1.5%, and severe bleeding 1.5%. There were no nonelective tricuspid valve reinterventions, major access site and vascular complications, major cardiac structural complications, or device embolizations. NYHA class I/II was achieved in 55.8%, 6-minute walk distance improved by 38.2 m (p < 0.001), and Kansas City cardiomyopathy questionnaire scores improved by 13.4 points (p < 0.001). CONCLUSION: Experience with the PASCAL transcatheter valve repair system in a European post-market setting confirms favorable safety and effectiveness at 30 days. TR significantly reduced, and clinical, functional, and quality-of-life outcomes significantly improved. This study is ongoing. Clinical Trial Registration: The study is ongoing and registered on ClinicalTrials.gov as NCT04614402. The current analysis is an interim report.

[Analysis of the characteristics of MRI T2 value changes of the muscles around the knee joint before and after the race in amateur marathon runners based on T2 mapping].

Objective: To evaluate the characteristics of MRI T2 value changes of muscles around the knee joint in amateur marathon athletes based on T2 mapping. Methods: A total of 12 amateur marathon runners (5 males and 7 females) were recruited as the marathon group, aged from 21 to 37(27.5±5.4) years. MRI examination of bilateral knee joint was performed one week before the race, within 12 hours after the race and two months after the race, respectively. Fifteen healthy volunteers (5 males and 10 females) were recruited as the control group, aged from 24 to 27(24.9±1.0) years, and underwent MRI examination of both knee joints. The T2 mapping imaging sequence was used to measure the T2 values of the sartorius, vastus medialis, biceps femoris, semimembranosus, medial head of gastrocnemius and lateral gastrocnemius head on the post-processing platform, and analyzed the marathon group before and after the race. The differences in the T2 value of each muscle of the marathon group before and after the race within 12 hours, before and 2 months after the race, and between the control group and the marathon group before the marathon were analyzed. Results: All subjects had not knee joint pain during the examination. Routine MRI examination showed that there was no obvious abnormality in the shape and signal of the muscles around the knee joint. The T2 value of the semimembranosus [(34.3±2.8) ms vs (35.5±2.5) ms, P=0.008], medial head of gastrocnemius [(34.1±3.4) ms vs (37.7±3.1) ms,P<0.001] and lateral head of gastrocnemius [(35.2±2.9) ms vs (37.2±3.9) ms,P=0.011] increased after the competition compared with that of pre-competition in the marathon group, while the T2 value of the remaining muscles showed no significant difference compared with that of pre-competition(P>0.05). At the follow-up of 2 months, the T2 value of semimembranosus remains higher than before the marathon [(34.3±2.8) ms vs (35.4±2.5) ms,P=0.043], and the T2 value of the medial head of the gastrocnemius and lateral head of gastrocnemius showed no statistically difference compared with pre-competition (P>0.05). Compared with the control group, the T2 value of the lateral head of the gastrocnemius in the marathon group was decreased [(35.3±3.0) ms vs (38.5±4.1) ms,P=0.007]. There was no significant difference in the T2 value of the remaining muscles in the marathon group (P>0.05). Conclusions: After the marathon, the changes in the T2 value of the muscles around the knee joint is reversible. T2 mapping imaging sequence can indirectly reflect the changes of skeletal muscle microstructure to a certain extent.

Whole-lesion histogram analysis of mono-exponential and bi-exponential diffusion-weighted imaging in differentiating lung cancer from benign pulmonary lesions using 3 T MRI.

AIM: To investigate whether whole-lesion histogram analysis of apparent diffusion coefficient (ADC) values derived from mono-exponential and bi-exponential diffusion-weighted imaging (DWI) can differentiate lung cancer from benign pulmonary lesions. MATERIALS AND METHODS: Thirty-two patients with lung cancer and 17 patients with benign pulmonary lesions were included retrospectively. All patients underwent DWI before surgery or biopsy. ADC histogram parameters, including mean, percentile values (10th and 90th), kurtosis, and skewness, were calculated independently by two radiologists. The histogram parameters were compared between patients with lung cancer and benign lesions. Receiver operating characteristic curves were constructed to evaluate the diagnostic performance. RESULTS: The ADCMean, ADC10th, DMean, D10th were significantly lower in lung cancer (1.187 ± 0.144 × 10-3; 0.440 ± 0.062 × 10-3; 1.068 ± 0.108 × 10-3; and 0.422 ± 0.049 × 10-3 mm/s) compared to benign lesions (1.418 ± 0.274 × 10-3; 0.555 ± 0.113 × 10-3; 1.216 ± 0.149 × 10-3; and 0.490 ± 0.044 × 10-3 mm/s; p<0.05). The ADCSkewness and DSkewness were significantly different between lung cancer (2.35 ± 0.72; 2.58 ± 1.14) and benign lesions (1.85 ± 0.54; 1.59 ± 1.47; p<0.05). D10th was robust in differentiating lung cancer from benign lesions. Using 0.453 × 10-3 mm/s as the optimal threshold, the sensitivity, specificity, and accuracy of D10th were 78.12%, 82.35%, and 79.6%, respectively. CONCLUSION: Whole-lesion histogram analysis of ADC values derived by mono-exponential and bi-exponential DWI using 3 T magnetic resonance imaging helps distinguish lung cancer from benign pulmonary lesions.

[Evaluation of refractory monosymptomatic nocturnal enuresis with ambulatory urodynamics monitoring and conventional urodynamics].

Objective: To explore the clinical value of ambulatory urodynamics monitoring (AUM) in the diagnosis and treatment of children with refractory monosymptomatic nocturnal enuresis (RMNE) by comparing the urodynamic parameters of AUM with those of conventional urodynamics (CUD). Methods: A total of 40 children (22 males and 18 females) diagnosed with RMNE in the First Affiliated Hospital of Zhengzhou University from May 2017 to September 2019 were collected. They were aged 9-16 years, and their frequency of nocturnal bed-wetting was≥2 times per week. CUD and one sleep cycle AUM were performed, respectively. Then, the urodynamic parameters were recorded and analyzed. Results: Five of the 40 children dropped out of the study because of the poor compliance. The age of children with RMNE was(12.6±2.1)years old, the ratio of male to female was 19∶16, and the severity of enuresis (enuresis frequency) was(4.2±1.7) times per week. Compared to the CUD group, the bladder compliance (BC) [(28.4±7.7) ml/cmH2O vs (23.6±6.1) ml/cmH2O(1 cmH2O=0.098 kPa)] and maximum detrusor pressure (Pmax.det) [(44.6±9.1) cmH2O vs (36.8±8.3) cmH2O] in the AUM group were significantly higher (P<0.05). The maximum flow rate (Qmax) [(19.6±7.2) ml/s vs (20.9±5.4) ml/s] and post void residual (PVR) [(9.5±5.7) ml vs (10.9±5.3) ml] between the two groups showed no statistically significant differences (P>0.05). Detrusor overactivity (DO) was detected in 27 cases (77.1%) during AUM and in 16 cases (45.7%) during CUD; the difference was statistically significant (P<0.05). Among them, 15 cases (42.9%) with DO were detected both in CUD and AUM, while 12 (34.3%) with DO were not detected in CUD. For the 15 cases with DO detected by both CUD and AUM, the frequency [(3.1±1.0) times/h vs (2.4±0.8) times/h] and maximum value of DO [(22.9±4.5) cmH2O vs (19.2±4.0) cmH2O] in the AUM group were both higher than those in the CUD group (P<0.05). Conclusions: Bladder dysfunction can be diagnosed in children with RMNE using AUM. Furthermore, AUM is more accurate than CUD in evaluating BC, Pmax.det, DO, and other parameters. For children with RMNE and with unsatisfactory CUD results, further AUM examination is recommended to clarify the etiology.

Machine Learning Reveals the Seismic Signature of Eruptive Behavior at Piton de la Fournaise Volcano.

Volcanic tremor is key to our understanding of active magmatic systems, but due to its complexity, there is still a debate concerning its origins and how it can be used to characterize eruptive dynamics. In this study we leverage machine learning techniques using 6 years of continuous seismic data from the Piton de la Fournaise volcano (La Réunion island) to describe specific patterns of seismic signals recorded during eruptions. These results unveil what we interpret as signals associated with various eruptive dynamics of the volcano, including the effusion of a large volume of lava during the August-October 2015 eruption as well as the closing of the eruptive vent during the September-November 2018 eruption. The machine learning workflow we describe can easily be applied to other active volcanoes, potentially leading to an enhanced understanding of the temporal and spatial evolution of volcanic eruptions.

[Comparative imaging study of mediastinal lymph node from pre-surgery dual energy CT versus post-surgeron verifications in non-small cell lung cancer patients].

OBJECTIVE: To validate the value of dual energy CT (DECT) in the differentiation of mediastinal metastatic lymph nodes from non-metastatic lymph nodes in non-small cell lung cancer (NSCLC). METHODS: In the study, 57 surgically confirmed NSCLC patients who underwent enhanced DECT scan within 2 weeks before operation were enrolled. Two radiologists analyzed the CT images before operation. All mediastinal lymph nodes with short diameter≥5 mm on axial images were included in this study. The morphological parameters [long-axis diameter (L), short-axis diameter (S) and S/L of lymph nodes] and the DECT parameters [iodine concentration (IC), normalized iodine concentration (NIC), slope of spectral hounsfield unit curve (λHU) and effective atomic number (Zeff) in arterial and venous phase] were measured. The differences of morphological parameters and DECT parameters between metastatic and non-metastatic lymph nodes were compared. The parameters with significant difference were analyzed by the Logistic regression model, then a new predictive variable was established. Receiver operator characteristic (ROC) analyses were performed for S, NIC in venous phase and the new predictive variable. RESULTS: In 57 patients, 49 metastatic lymph nodes and 938 non-metastatic lymph nodes were confirmed by surgical pathology. A total of 163 mediastinal lymph nodes (49 metastatic, 114 non-metastatic) with S≥5 mm were detected on axial CT images. The S, L and S/L of metastatic lymph nodes were significantly higher than those of non-metastatic lymph nodes (P < 0.05). The DECT parameters of metastatic lymph nodes were significantly lower than those of non-metastatic lymph nodes (P < 0.05). The best single morphological parameter for differentiation between metastatic and nonmetastatic lymph nodes was S (AUC, 0.752; threshold, 8.5 mm; sensitivity, 67.4%; specificity, 73.7%; accuracy, 71.8%). The best single DECT parameter for differentiation between metastatic and nonmetastatic lymph nodes was NIC in venous phase (AUC, 0.861; threshold, 0.53; sensitivity, 95.9%; specificity, 70.2%; accuracy, 77.9%). Multivariate analysis showed that S and NIC were independent predictors of lymph node metastasis. The AUC of combined S and NIC in the venous phase was 0.895(sensitivity, 79.6%; specificity, 87.7%; accuracy, 85.3%), which were significantly higher than that of S (P < 0.001) and NIC (P=0.037). CONCLUSIONS: The ability of quantitative DECT parameters to distinguish mediastinal lymph node metastasis in NSCLC patients is better than that of morphological parameters. Combined S and NIC in venous phase can be used to improve preoperative diagnostic accuracy of metastatic lymph nodes.

[Protective effect of cardiopulmonary fitness on patients with high risk of atherosclerotic cardiovascular disease].

OBJECTIVE: To evaluate the effects of cardiopulmonary fitness on arteriosclerotic cardiovascular disease (ASCVD) events in patients with different risks of ASCVD. METHODS: This study enrolled 544 non ASCVD patients who underwent cardiopulmonary exercise testing in Peking University Third Hospital from September 2016 to April 2018. ASCVD overall risk assessment was conducted according to "Chinese Guidelines for the Prevention and Treatment of Adult Dyslipidemia". Peak oxygen uptake (VO2peak), the classic indicator of cardiopulmonary fitness, was accurately determined by cardiopulmonary exercise testing in all the patients. All of the patients were followed up clinically. RESULTS: In the study, 506 patients completed the follow-up (250 lowrisk patients, 93 moderaterisk patients and 163 highrisk patients). The median follow-up period was 19 months (9-28 months), and 51 patients developed ASCVD events during the follow-up period, of whom, 33 cases developed myocardial infarction, unstable angina or coronary revascularization, and 18 cases ischemic stroke, transient ischemic attack or carotid vascular revascularization. The patients were divided into the ASCVD group (n=51) and the non ASCVD group (n=455) based on the presence or absence of ASCVD events. VO2peak [16.3 (3.6) mL/(kg·min) vs. 19.1 (3.2) mL/(kg·min), P<0.001] in the ASCVD group were significantly lower than that in the non ASCVD group. Logistic regression analysis found VO2peak [OR 0.893 (95%CI: 0.831-0.959), P=0.002] and ASCVD risk stratification [OR 1.428 (95%CI:1.028-1.878), P=0.031] were both independently associated with the occurrence of ASCVD events, which meant that every 1 mL/(kg·min) of increase in VO2peak, the risk of ASCVD events was reduced by 11%. The patients were divided into low, moderate, and high VO2peak according to the tertiles of their VO2peak [14.4 mL/(kg·min), and 23.0 mL/(kg·min)]. Logistic regression analyses were performed using ASCVD events as a dependent variable in the patients with highrisk and low/moderate-risk of ASCVD respectively. In the patients with highrisk of ASCVD, the results suggested that the incidence of ASCVD events was significantly decreased in the patients with moderate VO2 peak [OR 0.210 (95%CI: 0.054-0.814), P=0.024] and high VO2 peak [OR 0.146 (95%CI:0.025-0.870), P=0.035], but no significant effect of VO2 peak elevation on the incidence of ASCVD events was found in the low/moderate-risk ASCVD patients. CONCLUSION: High cardiopulmonary fitness can significantly reduce the occurrence of ASCVD events in patients with high-risk of ASCVD.

[Surgical treatment of tricuspid valve disease due to permanent pacemaker lead].

Objective: To summarize the etiology and surgical treatment experience of tricuspid valve disease due to permanent pacemaker lead. Methods: The medical records of 22 patients who underwent tricuspid valve operation for tricuspid valve disease due to permanent cardiac pacemaker lead from January 2008 to December 2017 were retrospectively reviewed. There were 12 males and 10 females, with a mean age of (62.6±12.1) years old (45-82 years old). All patients underwent tricuspid valve surgery via open thoracotomy under general anesthesia, including 8 patients through median thoracotomy approach, 4 patients through right mini-thoracotomy approach, and 10 patients with endoscopy-assisted and totally endoscopic technique. Moreover, 8 patients underwent tricuspid valve replacement, and 14 patients received tricuspid valve repair. Results: During the operation, 10 cases of severe tricuspid regurgitation were detected due to valve and subvalvular structures dysfunction involved in the pacing electrode, 7 cases showed tricuspid annulus dilation, and pacing electrode-related infective endocarditis were involved in the tricuspid valve of 5 cases. Compared with conventional median thoracotomy surgery, the amount of postoperative drainage fluid and hospitalization time after minimally invasive surgery (including right mini-thoracotomy and endoscopic surgery) were significantly reduced [281(120, 489) ml vs 368(180, 560) ml, P=0.02; 9.2(4.8, 14.5) d vs 11.2(6.3, 16.9) d, P=0.03]. Postoperative echocardiographic data showed that the size of the right atrium and ventricle in these patients was significantly reduced compared with preoperative data, and their cardiac function were normal. There was no difference of pacing electrode parameters between pre-and postoperative period. All 22 patients were cured and discharged, with no valve-and pacemaker-related complications. Conclusions: Patients with tricuspid valve disease due to permanent cardiac pacemaker lead should actively undergo surgery including tricuspid replacement or repair according to different etiologies, which exhibit satisfactory outcomes. Minimally invasive endoscopic tricuspid surgery is a new technique for the treatment of isolated tricuspid valve disease, with less surgical trauma and faster recovery.

[Primary skull base chondrosarcoma: a clinicopathological analysis].

Objective: To investigate the clinicopathological features, immunophenotype, molecular characteristics and differential diagnosis of primary skull base chondrosarcoma. Methods: Nine cases of primary skull base chondrosarcoma were collected at the First Affiliated Hospital of Fujian Medical University, from January 2006 to June 2019, reviewed for the clinical and radiologic data and morphologic features, immunophenotype and molecular characteristics. Results: Among all the 9 cases, six were male, three were frmale, with average age 47 years, and median age 47 years; five cases were WHO gradeⅠ, and four were WHO grade Ⅱ. Microscopically, the tumor showed lobulated growth pattern with low-medium cellularity within a chondroid or mucoid background. The tumor cells showed mild-moderate atypia, with binucleated forms, and mitosis was rare or occasional. Immunohistochemistry (IHC) showed tumor cells were positive for S-100 protein, vimentin, SOX-9 and D2-40, and negative for Brachyury, CK, EMA and CK8/18; the Ki-67 index was low (1% to 5%). Molecular analysis showed IDH1 R132C mutation in four cases. Conclusions: Skull base chondrosarcoma is a rare cartilaginous malignant tumor with a good prognosis. Its characteristic morphologies, combined with IHC and molecular detection are helpful for the differential diagnosis.

[Effects of ticagrelor on cardiorespiratory fitness in patients after percutaneous coronary intervention].

Objective: To investigate the effects of ticagrelor on cardiorespiratory fitness in patients with coronary heart disease after percutaneous coronary intervention (PCI). Methods: A total of 1 073 patients, who were diagnosed as coronary heart disease and underwent cardiopulmonary exercise testing (CPET) within 1 year after PCI, were enrolled from September 2017 to September 2019 in Peking University Third Hospital, including 309 patients in ticagrelor group and 764 patients in clopidogrel group. Clinical information, blood test results, echocardiographic parameters, cardiorespiratory fitness related parameters (including peak oxygen uptake (VO(2)), anaerobic threshold VO(2), peak oxygen pulse (VO(2)/HR) and carbon dioxide ventilation equivalent (VE/VCO(2)) slope), coronary lesions and intervention information were obtained. Cardiopulmonary fitness related indexes were compared between the two groups, and the correlation between ticagrelor use and cardiopulmonary fitness related indexes was analyzed by multivariate logistic regression. Patients who underwent CPET within 1 month after PCI were included in the subgroup analysis. Results: In ticagrelor group, the age was (60.3±10.3) years, and 253(81.9%) cases were male. The age of clopidogrel group was (60.6±10.0) years, and there were 608(79.6%) males. No significant differences were observed in peak VO(2), anaerobic threshold VO(2), and peak VO(2)/HR between the two groups (all P>0.05), but the VE/VCO(2) slope was significantly higher in the ticagrelor group than in the clopidogrel group (30.075 (27.207, 33.603) vs. 28.853 (25.970, 32.336), P<0.001). Logistic regression analysis suggested that the peak VO(2), anaerobic threshold VO(2) and peak VO(2)/HR were not significantly correlated with the ticagrelor use (all P>0.05), while the VE/VCO(2) slope was independently correlated with ticagrelor use (OR=1.098, 95%CI 1.032-1.168, P=0.003). Subgroup analysis of patients who underwent CPET within 1 month after PCI also indicated that no significant difference were observed in peak VO(2), anaerobic threshold VO(2), peak VO(2)/HR and VE/VCO(2) slope between the two groups (all P>0.05). Logistic regression analysis suggested that the peak VO(2), anaerobic threshold VO(2) and peak VO(2)/HR were not significantly correlated with ticagrelor use (all P>0.05), while the VE/VCO(2) slope was significantly correlated with ticagrelor use (OR=1.132, 95%CI 1.030-1.244, P=0.010). Conclusion: Among coronary heart disease patients after PCI, treatment with clopidogrel does not result in significant decrease in exercise endurance as compared with patients treated with ticagrelor.

[Relationship between angiopoietin-2 and vascular endothelial factor and vasodilation function in hypertensive patients].

Objective: To analyze the relationship between angiopoietin 2 (Ang2) and vascular endothelial factor and vasodilation function in hypertensive patients. Methods: Patients with new onset grade 1~2 hypertension (n=40) and healthy control group (n=25) wereenrolledprospectively. Serum Ang2 and nitric oxide (NO), nitric oxide synthase (eNOS), endothelin-1 (ET-1) were measured in both groups. Flow-mediated vasodilation (FMD) were measured in hypertensive patients. The above indicators were reviewed in hypertensive patients after antihypertensive treatment until blood pressure<140/90 mmHg. Results: Compared with the control group, serum Ang2 (P=0.049) and ET-1 (P<0.001) were significantly higher. Serum NO (P<0.001) and eNOS (P<0.001) was significantly lower in the hypertensive group. Compared with baseline, serum Ang2 (P=0.049) and ET-1 (P<0.001) were decreased significantly, meanwhile serum NO (P<0.001) and eNOS (P<0.001) were significantly increased. Serum Ang2 after antihypertensive treatment was not significantly different from that of the control group, but no statistical difference was observed in FMD after antihypertensive therapy. Correlation analysis found that serum Ang2 was positively correlated with mean arterial pressure (R=0.432, P<0.001), and negative correlated with serum NO(R=-0.374, P=0.001) and FMD (R=-0.368 0, P=0.002). Multiple linear regression found that serum Ang2 was independently associated with body mass index, mean arterial pressure, and serum NO. Conclusion: Serum Ang 2 can reflect the degree of endothelial and vasodilation impairment in hypertensive patients. Antihypertensive therapy can improve endothelial function, but whether it can restore damaged vasodilation function needs further verification.

[The relationship between simple numerical function and gray matter volume in normal brain aging].

Objective: To explore the relationship between simple numerical function and gray matter volume (GMV) in normal brain aging using the voxel-based morphometry(VBM) approach. Methods: A total of 123 individuals from 18 to 70 years old (63 males,60 females,the average age was (43±14) years, were recruited from right-handed healthy Han Chinese volunteers at the Department of MRI at the First Affiliated Hospital of Zhengzhou University between October 2016 and June 2017. All subjects underwent magnetic resonance sagital three-dimensional imaging scanning, and statistical parameter graph (SPM) 8 software was used for voxel-based morphological analysis to compare the differences in gray matter volume between different age groups.Gray matter volume difference brain regions between different age groups were extracted as regions of interest, and correlation analysis was carried out on the score of simple numerical calculation to find the responsible atrophy brain regions related to the decline of simple digital computing ability. Results: The brain regions with different gray matter volume in different age groups mainly included bilateral frontal gyrus, bilateral anterior cingulate gyrus, bilateral middle cingulate gyrus, bilateral olfactory cortex, bilateral caudate nucleus and bilateral insula. Among them the GMV of bilateral superior frontal gyrus and anterior cingulate gyrus showed the strongest correlation with the simple numerical function. Before removing the effect of age, the correlation between the GMV of the bilateral superior frontal gyrus and medial cingulate gyrus and the corrected count of correct was significant (r=0.403,P=0.000), the correlation between GMV and the percent of correct was also significant (r=0.229,P=0.037).After removing age as a covariate, bilateral superior frontal gyrus and central cingulate gyrus were still positively correlated with the correct number after correction of simple numerical calculation function (r=0.225,P=0.014) and the correct percentage (r=0.245, P=0.007). Conclusion: There is extensive gray matter volume atrophy during the normal brain aging process. The decrease of simple numerical function in normal brain aging may be related to the decrease of frontal and anterior cingulate gray matter volume.

[Clinical application of TCGA molecular classification in endometrial endometrioid carcinoma].

Objective: To explore molecular characteristics of endometrial endometrioid cancer according to The Cancer Genome Atlas (TCGA) based molecular classification of endometrial carcinomas and to confirm simple and clinically applicable surrogate methodologies in pathological practice. Methods: Two hundred and twenty-eight cases of endometrial endometroid adenocarcinomas (EnACs) collected from August 2001 to August 2017 from Peking University Health Science Center, Peking University Third Hospital were molecularly categorized by using Sanger sequencing for the exonuclease domain mutations (EDM) of POLE, and by immunohistochemistry for p53 and mismatch repair (MMR) proteins. The cohort was classified into polymerase-E exonuclease domain mutation (POLE EDM), mismatch repair deficiency (MMR-D), p53 abnormal (p53-abn) and p53 wild type (p53-wt) groups. The correlation between molecular subgroups and the clinical-pathological features including prognosis were analyzed. Results: The cohort was distributed as follows: 11(4.8%) POLE EDM, 47(20.6%) MMR-D, 9(4.0%) p53-abn and 161(70.6%) p53-wt. p53-wt subgroup patients demonstrated significantly higher lymph node metastasis (P=0.011) and more advanced stage (P=0.036) than those of somatic hypermutation group cases (POLE EDM and MMR-D). In the FIGO grade 2-3 EnACs cohort, TCGA molecular subtyping was significantly correlated with progression-free survival and overall survival (P=0.043). POLE EDM subgroup had the best survival, while p53-abn subgroup had the worst. Conclusions: Identification of POLE EDM and MMR-D subgroups provides independent and highly valuable prognostic information beyond established histological classification. Based on immunohistochemistry of MMR, p53 and POLE mutational analysis, this pragmatic molecular classification scheme can be served as a reliable surrogate for TCGA molecular classification, which has potential to be used routinely in Chinese pathological practice.

[Mode of median nerve irritation under different wrist forcing postures observed by ultrasonography and foot pressure measurement system].

Objective: To analyze the influence of simulation mouse use motion under different wrist forcing postures on median nerve, tendons and ligaments in the carpal tunnel. Methods: From June to November in 2017, a total of 49 healthy volunteers [aged from 18 to 27 years, 24 males (48 cases of hands) and 25 females (50 cases of hands)] were selected in the Institute of Digitized Medicine and First Affiliated Hospital of Wenzhou Medical University.Three hand postures of the volunteers were simultaneously and continuously measured by using LOGIQ E9 ultrasonic diagnostic apparatus and Zebris foot pressure distribution measurement system.Seventeen parameters of nerves, tendons and ligaments in carpal tunnel were observed under natural (0 N), and two forced (25 and 50 N) states.Double factor variance analysis was performed with generalized estimating equation (GEE). Results: With increasing pressure (0, 25 and 50 N) of hand postures, the distance between median nerve and transverse carpal ligament were all less than 0.2 cm.The differences in both the distance between median nerve and flexor pollicis longus under the hand pressure changes or under the hand posture changes and the top angle of a triangle composed of median nerve, flexor pollicis longus and flexor digitorum superficialis group under the hand pressure changes or under the hand posture changes were all significant under the GEE analysis (all P<0.01). There were no significant changes in all other structural parameters in the carpal tunnel with the increasing of hand pressure (all P>0.05). Conclusions: The influence of the transverse carpal ligament to the median nerve belongs to the mechanism of pressure-induced irritation damage.The influence of flexor pollicis longus to median nerve belongs to the mechanism of tension-induced irritation damage.The influence of flexor digitorum superficialis to median nerve belongs to the mechanism of mixed shear irritation damage.

Electron Shock Ignition of Inertial Fusion Targets.

It is shown that inertial confinement fusion targets designed with low implosion velocities can be shock-ignited using laser-plasma interaction generated hot electrons (hot-e's) to obtain high energy gains. These designs are robust to multimode asymmetries and are predicted to ignite even for significantly distorted implosions. Electron shock ignition requires tens of kilojoules of hot-e's which can be produced only at a large laser facility like the National Ignition Facility, with the laser-to-hot-e conversion efficiency greater than 10% at laser intensities ∼10^{16} W/cm^{2}.

The effectiveness of low-level laser therapy as an adjunct to non-surgical periodontal treatment: a meta-analysis.

BACKGROUND AND OBJECTIVES: Although low-level laser therapy (LLLT) has been demonstrated to have a biomodulatory effect on periodontal tissue, no systematic review has exclusively addressed its effectiveness as an adjunct to non-surgical periodontal treatment. This study aimed to evaluate whether an additional benefit exists for the application of LLLT compared with scaling and root planing (SRP) alone. MATERIAL AND METHODS: An extensive search was conducted in the Cochrane Library (Issue 8, 2015), PubMed (1997) and EMBASE (1947) before August 2015 for randomized controlled trials (RCTs). The bias risk was assessed with the Cochrane tool for risk of bias evaluation. A meta-analysis was performed using REVMAN 5.3. RESULTS: After independent screening of 354 initial records, eight publications (seven RCTs) were included. However, six were rated as 'having a high risk of bias' as a result of major methodological weakness in 'allocation concealment' and 'blinding of key personnel'. Meta-analysis showed that LLLT-mediated SRP demonstrated significant short-term benefits over SRP monotherapy in the improvement of the probing pocket depth (p = 0.0009 at 1 mo; p = 0.03 at 2 mo) and the level of interleukin-1ß in the gingival crevicular fluid (p = 0.01 at 1 mo). Nevertheless, LLLT failed to show significant additional intermediate-term (3 and 6 mo) effects in terms of clinical parameters and alveolar bone density. CONCLUSION: These findings indicated that LLLT showed only short-term additional benefits after conventional SRP. Its long-term effects remain unclear due to substantial methodological weaknesses and an insufficient number of current studies. Future RCTs with better designs and longer follow-up periods are required to assess the effectiveness of LLLT as an adjunctive treatment strategy in patients with periodontal disease.

Real-Time Tracking of Single and Multiple Objects from Depth-Colour Imagery Using 3D Signed Distance Functions.

We describe a novel probabilistic framework for real-time tracking of multiple objects from combined depth-colour imagery. Object shape is represented implicitly using 3D signed distance functions. Probabilistic generative models based on these functions are developed to account for the observed RGB-D imagery, and tracking is posed as a maximum a posteriori problem. We present first a method suited to tracking a single rigid 3D object, and then generalise this to multiple objects by combining distance functions into a shape union in the frame of the camera. This second model accounts for similarity and proximity between objects, and leads to robust real-time tracking without recourse to bolt-on or ad-hoc collision detection.