[Correlation between total cerebral small vessel disease score and retinal vessel diameters in patients with mild stroke].

Objective: To explore the relationship between the total cerebral small vessel disease (CSVD) score and retinal vessel diameters in patients with mild stroke. Methods: The patients with mild stroke who were hospitalized in the Second People's Hospital of Changzhou, Nanjing Medical University from March to December 2019 were continuously collected (National Institutes of Health Stroke Scale score≤3 points). All patients completed the head magnetic resonance imaging and retinal fundus photography examination, and then the retinal arteriovenous diameter was measured semi-automatically based on the pictures. According to the total CSVD score (0-4 points), the patients were divided into 5 groups. The baseline characteristics of the patients were compared. Moreover, the correlation of total CSVD with retinal blood vessel diameters were analyzed by spearman and linear regression. Results: A total of 206 patients were enrolled. There were 69, 51, 41, 30, and 15 patients with 0, 1, 2, 3, and 4 points, respectively. In CSVD subgroups, there were significant differences in age, duration of hypertension and diabetes (all P<0.05). The central retinal artery equivalent (CRAE), (CSVD scores 0-4 were (126±12) µm, (118±11) µm, (108±11) µm, (99±8) µm, (90±7) µm, P<0.001) and arteriole-to-venule ratio (AVR) (CSVD scores 0-4 were 0.65±0.05, 0.60±0.04, 0.56±0.04, 0.49±0.03, 0.44±0.02, P<0.001) were different in CSVD subgroups. With the increase of CSVD score, the diameter of artery and AVR became smaller. The total CSVD was significantly correlated with AVR by Spearman correlation analysis (r= 0.818, P<0.001). By constructing a linear regression equation model, the coefficient of determination of the total CSVD score (R2=0.694) was higher than that of lacunes, white matter hyperintensities, cerebral microbleeds and enlarged perivascular space. After adjusting for age, course of hypertension and diabetes, and different types of CSVD, further multiple linear regression analysis revealed that the total CSVD score was still an independent related factor of AVR (ß=-0.039, P<0.001, 95%CI=-0.051--0.028). Conclusions: Total CSVD score is negatively correlated with retinal artery diameters and AVR. Additionally, the total CSVD score can better reflect the degree of cerebral microvascular lesions than single type CSVD.

[The clinical application of blood routine and liver and kidney function test in COVID-19 disease prediction].

Objective: To explore the clinical application value of routine indicators such as blood routine and liver and kidney function in auxiliary diagnosis and prognosis of COVID-19 patients. Methods: SNK-q and other methods were used to retrospectively analyzed the differences of blood routine test, liver and kidney function and other inflammatory indexes of 30 patients with covid-19, 29 patients with other viral pneumonia, 35 patients with influenza A/B and 25 healthy persons from January 28 to February 14, 2020 in Xiangya Hospital of Central South University. Results: The neutrophils count increased gradually in COVID-19 group, influenza A/B group and other types of viral pneumonia group, and the difference between COVID-19 group and other viral pneumonia groups was statistically significant(H=-19.064,P<0.05); The lymphocyte count decreased gradually in the control group, influenza A/B group, other viral pneumonia group and COVID-19 group. In addition, DB, UA and GLU were also different among groups. Subgroup analysis showed that there were statistically significant differences in N(F=9.581,t=-0.152,P<0.05), N%(F=5.723,t=-0.600, P<0.05), NLR(F=4.773, t=-1.161, P<0.05), PCT(F=17.464, t=-1.477, P<0.05)and CRP(F=7.656, t=-1.973, P<0.05) between patients with lung involvement +-++ and patients with lung involvement +++-++++. There were statistically significant differences in NLR(F=63.931, t=-2.815, P<0.01), AST(F=15.704, t=-1.930, P<0.01), ALT(F=35.551, t=-2.199, P<0.01), LDH(F=7.715, t=-2.703, P<0.05) and GLU(F=6.306, t=-5.116, P<0.05) between the light+common subgroup and the heavy+critical subgroup of COVID-19 clinical classification. Correlation analysis showed that clinical stage and imaging credit period were significantly correlated with NLR (r=0.406, P=0.026; r=0.397, P=0.030), ALT (r=0.403, P=0.049; r=0.418, P=0.047), LDH (r=0.543, P<0.01; r=0.643, P<0.01) and GLU(r=0.750, P<0.01; r=0.471, P=0.042). A total of 5 principal components were extracted from all the included indicators, and the comprehensive information extraction rate was 82.86%. Indicators of a large load included Ur, PCT and CRP in PC1; ALT, AST and GLU in PC2; N%, L%, L and NLR in PC3. It indicated that the indicators of acute infection, liver function and blood routine had certein warning effect on disease surveillance. The results of ROC curve analysis showed that the combined detection of N+TB+Urea was the best practice to distinguish COVID-19 and other viral pneumonia, while the combined detection of N+L+UA was the most effective solution to make a distinction between COVID-19 and influenza A/B patients. In the aspect of disease evaluation, NL+LDH+GLU+ALT combined detection represent the best diagnostic performance to distinguish the clinical stage of light+common type and heavy+critical type, achieving the AUC (ROC) to 0.904, with the sensitivity 75% and the specificity 100% at the cut-off value of 0.477. Conclusion: In addition to etiology and imaging examination, doctors can also improve the routine laboratory tests such as blood routine test, liver and kidney function to assist diagnosis and disease prediction of patients with respiratory tract infection.

[Effects of preoperative segmental mobility on the clinical and radiographic outcomes following one-level artificial cervical disc replacement].

Objective: To investigate the effects of preoperative segmental range of motion (ROM) on clinical and radiographical outcomes after artificial cervical disc replacement (ACDR) and explore whether ACDR could be indicated for patients with preoperative limited or excessive segmental ROM. Methods: From January 2008 to December 2017, patients who underwent Prestige-LP ACDR in West China Hospital were retrospectively reviewed. The preoperative and postoperative X-rays of the cervical spine were collected to measure the radiographic parameters, including cervical lordosis (CL), C(2-7) ROM, disc height (DH), disc angle (DA) and ROM at the arthroplasty level. Clinical outcomes were evaluated using the Japanese Orthopedic Association (JOA) and the Neck Disability Index (NDI) scores. The correlation between preoperative segmental ROM and postoperative clinical and radiographical outcomes were also analyzed. Results: A total of 161 patients were analyzed, with 73 males and 88 females. The mean age was (44±8) years, and the follow-up period was 34 months (12-120 months). JOA and NDI scores improved after ACDR (P<0.05). However, postoperative C(2-7) ROM and ROM at the arthroplasty level were comparable with preoperative counterparts (both P>0.05). Preoperative segmental ROM positively correlated with C(2-7) ROM and ROM at the arthroplasty segment (r=0.213、0.271, both P<0.05), but was negatively correlated with the change of ROM (r=-0.534, P<0.05). The segmental ROM was 4.0°±1.0° in the limited-ROM group (A) and 14.6°±1.3° in the excessive-ROM group (B), respectively. There were significantly more patients diagnosed with cervical spondylosis in group A than in group B (35.5% vs 10.7%, P<0.05). The level-distribution was statistically different between the two groups. C(5/6) and C(6/7) were prone to limited motion in group A, while C(4/5) and C(5/6) were predisposed to excessive motion in group B (all P<0.05). After surgery, C(2-7) ROM increased for 14.2°±16.8° in group A, while paradoxically decreased for 2.2°±14.4° in group B. However, C(2-7) ROM in group B was still larger than that in group A (P<0.05). Similarly, the ROM at the arthroplasty level increased by 3.1°±3.7° in group A, whereas the values decreased by 4.4°±4.2° in group B postoperatively. In addition, group A still had less segmental ROM than group B (P<0.05). The preoperative DH in group A was less than that in group B (P<0.05). The rates of ASD, HO, and high-grade HO in group A were all higher than those in group B but without significant differences (all P>0.05). Conclusion: Preoperative segmental ROM has no significant effects on clinical outcomes after ACDR; it has a positive correlation with postoperative global and segmental ROM while is negatively correlated with ROM change.

Epigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer.

BACKGROUND: Utilization of alternative transcription start sites through alterations in epigenetic promoter regions causes reduced expression of immunogenic N-terminal peptides, which may facilitate immune evasion in early gastric cancer. We hypothesized that tumors with high alternate promoter utilization would be resistant to immune checkpoint inhibition in metastatic gastric cancer. PATIENTS AND METHODS: Two cohorts of patients with metastatic gastric cancer treated with immunotherapy were analyzed. The first cohort (N = 24) included patients treated with either nivolumab or pembrolizumab. Alternate promoter utilization was measured using the NanoString® (NanoString Technologies, Seattle, WA, USA) platform on archival tissue samples. The second cohort was a phase II clinical trial of patients uniformly treated with pembrolizumab (N = 37). Fresh tumor biopsies were obtained, and transcriptomic analysis was carried out on RNAseq data. Alternate promoter utilization was correlated to T-cell cytolytic activity, objective response rate and survival. RESULTS: In the first cohort 8 of 24 (33%) tumors were identified to have high alternate promoter utilization (APhigh), and this was used to define the APhigh tertile of the second cohort (13 APhigh of 37). APhigh tumors exhibited decreased markers of T-cell cytolytic activity and lower response rates (8% versus 42%, P = 0.03). Median progression-free survival was lower in the APhigh group (55 versus 180 days, P = 0.0076). In multivariate analysis, alternative promoter utilization was an independent predictor of immunotherapy survival [hazard ratio 0.29, 95% confidence interval 0.099-0.85, P = 0.024). Analyzing tumoral evolution through paired pre-treatment and post-treatment biopsies, we observed consistent shifts in alternative promoter utilization rate associated with clinical response. CONCLUSION: A substantial proportion of metastatic gastric cancers utilize alternate promoters as a mechanism of immune evasion, and these tumors may be resistant to anti-PD1 immune checkpoint inhibition. Alternate promoter utilization is thus a potential mechanism of resistance to immune checkpoint inhibition, and a novel predictive biomarker for immunotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT#02589496.

Unifying miscellaneous performance criteria for a prototype supercapacitor via Co(OH)2 active material and current collector interactions.

The use of transition metal oxides and hydroxides in supercapacitors can yield high specific capacity electrodes. However, the effect of interaction between active material and current collector has remained unexplored. Here the behaviour of electrodeposited hexagonal cobalt hydroxide nanosheets on a variety of substrates was investigated, and the resulting valence bonding, morphological evolutions and phase transformations examined. It is shown that the electrochemical activity of the face centred cubic (FCC) Ni substrate dramatically decreases cyclability, the FCC Cu substrate also demonstrates decreased performance, and hexagonal carbon nanofibre (CNF) and Ti substrates exhibit far more stability. The miscellaneous roles of valence bonding, redox reactions and crystal structure mismatch between active material and current collector are examined, and their consequences discussed. Using the resulting insights into performance criteria, it was possible to select a suitable substrate for the fabrication of an asymmetric supercapacitor. The high performance and stability of the device demonstrates the usefulness of this approach, and the utility of applying these insights to energy storage devices.