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Aim: To use multidetector row computed tomography (MDCT)-derived tricuspid annulus (TA) measurements to identify predictors for tricuspid regurgitation (TR) reduction after transcatheter aortic valve replacement (TAVR), and to investigate the impact of TR change on prognosis., Materials and Methods: A retrospective, single-centre study was conducted on consecutive patients who underwent TAVR with concomitant baseline mild or more severe TR from April 2012 to April 2022. TA parameters were measured using MDCT., Results: The study comprised 266 patients (mean age 74.2 ± 7.6 years, 147 men) and 45.1% had more than one grade of TR reduction at follow-up. Independent predictors of TR reduction at follow-up were distance between TA centroid and antero-septal commissure (odd ratio [OR] 0.776; 95% confidence interval [CI]: 0.672-0.896, p=0.001), baseline TR of moderate or worse (OR 4.599; 95% CI: 2.193-9.648, p<0.001), systolic pulmonary artery pressure (OR 1.018; 95% CI: 1.002-1.035, p=0.027), age (OR 0.955; 95% CI: 0.920-0.993, p=0.019), and pre-existing atrial fibrillation (OR 0.209; 95% CI: 0.101-0.433, p<0.001). Patients without TR reduction had higher rates of rehospitalisation (hazard ratio [HR] 0.642; 95% CI: 0.413-0.998, p=0.049)., Conclusions: The MDCT-derived TA parameter was predictive of TR reduction after TAVR. Persistent TR after TAVR was associated with higher rates of rehospitalisation., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Breast cancer diagnosis had been linked to an increased risk of melanoma in several reports. The aim of the current study was to assess the role of genetics, increased surveillance, and radiation treatment in patients with a dual diagnosis of breast cancer and melanoma (DBM)., Materials and Methods: All patients treated at Sheba Medical Center between 2007 and 2021 with DBM were included in the cohort. Data on family history, genetic tests, characteristics, and treatment of both cancers were collected. The proportion of patients with a pathogenic variant (PV) in BRCA1 and BRCA2 genes was compared to a control group of patients with breast cancer. The proportion of patients presenting with in-situ disease was compared to the national registry data., Results: The cohort included 222 DBM patients of whom 114 had documentation of genetic testing. Twenty patients tested positive for PVs of which 13 (11%) were in BRCA genes. This was comparable to the proportion in patients with a diagnosis of breast cancer (736; 19%). The proportion of melanoma diagnosed at stage 0 was comparable to the national proportion ( N  = 40; 30% vs. 28%, respectively). In comparison to the national registry, a larger proportion of breast cancers were ductal carcinoma in situ or lobular carcinoma in situ [10% in the registry vs. 19% (22) in the cohort; P  < 0.003]., Conclusions: In patients with DBM we did not find an increased proportion of PVs in BRCA genes. Our findings suggest that the increased standardized incidence ratio of the dual diagnosis may be partially explained by increased surveillance and detection of earlier-stage cancers., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. Retinol-binding protein 4 (RBP4) is an adipokine with pro-inflammatory effects. However, the change of RBP4 concentration and its role in sarcopenia remains unclear. The aim of this study was to evaluate the association of serum RBP4 level with sarcopenia in the older adults. A total of 816 community-dwelling older adults aged ≥60 years were enrolled. Serum RBP4 was measured by enzyme-linked immunosorbent assay. Appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed were measured. We found that serum RBP4 levels were higher in patients with sarcopenia when compared with those without sarcopenias (44.3 [33.9-57.7] vs 38.0 [28.0-48.4] μg/mL). Receiver operating characteristic curve analysis indicated that the optimal cutoff value of serum RBP4 level that predicted sarcopenia was 38.79 μg/mL with a sensitivity of 67.8% and a specificity of 53.3%. Multivariate logistic regression analysis showed that the subjects with a higher level of RBP4 had a higher risk of sarcopenia (adjusted odds ratio [OR] = 2.036, 95% CI = 1.449-2.861). Serum RBP4 concentration was negatively correlated with grip strength (r = -.098), gait speed (r = -.186), and AMSI (r = -.096). Moreover, serum RBP4 levels were higher in patients with severe sarcopenia when compared with those with moderate sarcopenia (49.0 [37.3-61.2] vs 40.4 [31.3-51.2] μg/mL). Taken together, our results demonstrate that serum RBP4 level is correlated with the risk and severity of sarcopenia in the older adults, indicating that RBP4 might serve as a surrogate biomarker for the screening and evaluation of sarcopenia., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: It is unknown whether the sex difference whereby female transcatheter aortic valve replacement (TAVR) candidates had a lower risk profile, a higher incidence of in-hospital complications, but more favorable short- and long-term survival observed in tricuspid cohorts undergoing TAVR would persist in patients with bicuspid aortic valves (BAVs)., Objectives: The aim of this study was to reexamine the impact of sex on outcomes following TAVR in patients with BAVs., Methods: In this single-center study, patients with BAVs undergoing TAVR for severe aortic stenosis from 2012 to 2021 were retrospectively included. Baseline characteristics, aortic root anatomy, and in-hospital and 1-year valve hemodynamic status and survival were compared between sexes., Results: A total of 510 patients with BAVs were included. At baseline, women presented with fewer comorbidities. Men had a greater proportion of Sievers type 1 BAV, higher calcium volumes (549.2 ± 408.4 mm 3 vs 920.8 ± 654.3 mm 3 ; P < 0.001), and larger aortic root structures. Women experienced more vascular complications (12.9% vs 4.9%; P = 0.002) and bleeding (11.1% vs 5.3%; P = 0.019) and higher residual gradients (16.9 ± 7.7 mm Hg vs 13.2 ± 6.4 mm Hg; P < 0.001), while men were more likely to undergo second valve implantations during index TAVR (6.3% vs 15.9%; P = 0.001). Death at 1 year was not significantly different between sexes (HR: 1.15; 95% CI: 0.56-2.35; P = 0.70). Bleeding (adjusted HR: 4.62; 95% CI: 1.51-14.12; P = 0.007) was the single independent predictor of 1-year death for women., Conclusions: In patients with BAVs undergoing TAVR, women presented with fewer comorbidities, while men had a greater proportion of type 1 BAV, more calcification, and larger aortic roots. In-hospital outcomes favored men, with fewer complications except for the need for second valve implantation, but 1-year survival was comparable between sexes., Competing Interests: Funding Support and Author Disclosures This work was supported by the National Natural Science Foundation of China (grants 81970325, 82170375, and 82102129); Sichuan Province Department of Science and Technology (grant number 2022YFS0364); West China Hospital “1·3·5” Discipline of Excellence Project “Percutaneous Transcatheter Aortic Valve Implantation” and “Mechanisms of Aortic Stenosis and the Clinical Applications”; and a fellowship of the China Postdoctoral Science Foundation (2020M683327). Drs Mao Chen and Feng are proctors and consultants for Venus MedTech, MicroPort, and Peijia Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To prepare the modified hyaluronic acid viscous hydrogel loaded with sliver particles and to explore the roles and mechanism of the hydrogel in healing of full-thickness skin defect wounds with bacterial colonization in mice. Methods: The experimental research method was adopted. Dopamine modified hyaluronic acid (HA-DA) and phenylboric acid modified hyaluronic acid (HA-PBA) were prepared, and their characteristic peaks were detected by Fourier-transform infrared spectroscopy. Different mass of acrylamides was added to HA-DA and HA-PBA to prepare the viscous hydrogel with mass fraction of acrylamide in 10%, 15%, and 20%. The gelation of the viscous hydrogel with mass fraction of acrylamide in 20% was observed in the state of tilt and inversion at 37 ℃, and the storage modulus and loss modulus of the above 3 kinds of viscous hydrogels were detected by rotational rheometer. The sliver-loaded viscous hydrogel was prepared by adding nano silver ions to the viscous hydrogel with mass fraction of acrylamide in 20%. The concentration of silver ions released by sliver-loaded viscous hydrogel was measured by inductively coupled plasma mass spectrometer, and the cumulative release rate of silver ion was calculated ( n =5). The mouse fibroblasts L929 were divided into phosphate buffered saline (PBS) group, viscous hydrogel group, and sliver-loaded viscous hydrogel group, which were dealt correspondingly, and the cell survival was detected by cell counting kit 8 method after 1, 2, and 3 d of culture ( n =5). Twenty-four male C57BL/6 mice aged 6-8 weeks were selected, and forty-eight full-thickness skin defect wounds were inflicted and inoculated with the mixture of Escherichia coli and Staphylococcus aureus in the back of the mice, with two wounds in each mouse. The wounds were divided into normal saline group, viscous hydrogel group, and sliver-loaded viscous hydrogel group, which were dealt correspondingly, with 16 wounds in each group, and two wounds in each mouse were divided into different groups. On post injury day (PID) 3, 7, 10, and 14, the wound healing was observed and the wound healing rate was calculated. On PID 3, the colony forming units of Escherichia coli and Staphylococcus aureus in wounds were observed and counted. On PID 14, the epithelized epidermal thickness and the optical density of collagen fiber in wounds were observed and analyzed after hematoxylin eosin staining and Masson staining, respectively. On PID 3, 7, and 10, the expressions of tumor necrosis factor α (TNF-α), transforming growth factor β 1 (TGF-β 1 ), and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry. The number of wounds in each index detecting at each time point was four. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, and Bonferroni correction. Results: The characteristic peaks of HA-PBA were detected at the wave numbers of 1 369 and 1 425 cm -1 , indicating that phenylboric acid had been successfully grafted on hyaluronic acid, and the characteristic peaks of HA-DA were detected at the wave numbers of 1 516 and 1 431 cm -1 , indicating that dopamine had been successfully grafted on hyaluronic acid. The viscous hydrogel with mass fraction of acrylamide in 20% maintained the stable and no-flow condition of gelation in the state of tilt and inversion at 37 ℃. The storage modulus and loss modulus of the viscous hydrogel increased with the increase of acrylamide content, the storage modulus and loss modulus of the 3 kinds of viscous hydrogels had no obvious changes with the increase of the oscillation frequency or time, and the storage modulus of the 3 kinds of acrylamide hydrogels were greater than the loss modulus. The release of silver ion in the sliver-loaded viscous hydrogel lasted for 7 days, and the cumulative release rate of silver ion was up to 65%. After 1, 2, and 3 d of culture, the cell survival rates in sliver-loaded viscous hydrogel group were significantly lower than those in PBS group and viscous hydrogel group ( P <0.05 or P <0.01), while after 1 d of culture, the cell survival rate in viscous hydrogel group was significantly lower than that in PBS group ( P <0.01). With extension of time after injury, the wounds of mice in the 3 groups shrank gradually. On PID 3, 7, 10, and 14, the wound healing rates in sliver-loaded viscous hydrogel group were (53.0±3.6)%, (75.3±6.9)%, (93.3±1.2)%, and (96.7±0.8)%, which were significantly higher than (21.8±6.4)%, (53.9±8.2)%, (72.0±7.8)%, and (92.5±0.4)% in normal saline group ( P <0.01). On PID 3 and 14, the wound healing rates in sliver-loaded viscous hydrogel group were significantly higher than (43.5±2.4)% and (94.1±1.5)% in viscous hydrogel group ( P <0.05). On PID 3 and 10, the wound healing rates in viscous hydrogel group were significantly higher than those in normal saline group ( P <0.01). On PID 3, the colony forming units of two bacteria in wound of sliver-loaded viscous hydrogel group were significantly less than those in normal saline group and viscous hydrogel group ( P <0.01), while the colony forming units of two bacteria in wound of viscous hydrogel group were significantly less than those in normal saline group ( P <0.05). On PID 14, the wounds were basically epithelialized and the epidermis was thicker, with collagen protein content being increased significantly and more orderly arranged collagen in sliver-loaded viscous hydrogel group compared with those in the other 2 groups. On PID 14, the epidermal thickness in wounds of sliver-loaded viscous hydrogel group was significantly increased compared with that in the other two groups ( P <0.05), and the optical density of collagen fiber was significantly increased compared with those in normal saline group ( P <0.05). On PID 3, the expressions of TGF-β 1 and VEGF in wounds of sliver-loaded viscous hydrogel group were significantly higher than those in normal saline group ( P <0.05 or P <0.01), while the expression of VEGF in wounds of viscous hydrogel group was significantly higher than that in normal saline group ( P <0.01). On PID 7, the expression of TGF-β 1 in wounds of sliver-loaded viscous hydrogel group was significantly higher than that in the other 2 groups ( P <0.01), and the expression of VEGF was significantly higher than that in normal saline group ( P <0.01). On PID 10, the expression of TNF-α in wounds of sliver-loaded viscous hydrogel group was significantly lower than that in normal saline group ( P <0.05), the expressions of TGF-β 1 and VEGF in wounds of sliver-loaded viscous hydrogel group were significantly higher than those in normal saline group ( P <0.05 or P <0.01), and the expression of VEGF in wounds of sliver-loaded viscous hydrogel group was significantly higher than that in viscous hydrogel group ( P <0.05). Conclusions: The sliver-loaded viscous hydrogel prepared in this study has good stability and elasticity, which can continuously release silver ions and help to accelerate the healing of full-thickness defect wounds with bacterial colonization in mice. Besides, the sliver-loaded viscous hydrogel has low biological toxicity and can promote re-epithelialization, collagen deposition as well as angiogenesis of wounds, which may be related to the infiltration and regression of inflammatory cells.

A formal risk assessment for identifying high-risk patients is essential in clinical practice and promoted in guidelines for the management of anterior acute myocardial infarction. In this study, we sought to evaluate the performance of different machine learning models in predicting the 1-year mortality rate of anterior ST-segment elevation myocardial infarction (STEMI) patients and to compare the utility of these models to the conventional Global Registry of Acute Coronary Events (GRACE) risk scores. We enrolled all of the patients aged >18 years with discharge diagnoses of anterior STEMI in the Western China Hospital, Sichuan University, from January 2011 to January 2017. A total of 1244 patients were included in this study. The mean patient age was 63.8±12.9 years, and the proportion of males was 78.4%. The majority (75.18%) received revascularization therapy. In the prediction of the 1-year mortality rate, the areas under the curve (AUCs) of the receiver operating characteristic curves (ROCs) of the six models ranged from 0.709 to 0.942. Among all models, XGBoost achieved the highest accuracy (92%), specificity (99%) and f1 score (0.72) for predictions with the full variable model. After feature selection, XGBoost still obtained the highest accuracy (93%), specificity (99%) and f1 score (0.73). In conclusion, machine learning algorithms can accurately predict the rate of death after a 1-year follow-up of anterior STEMI, especially the XGBoost model., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Li et al.)

Objective: To clarify the mechanism of heat shock protein 27 (HSP27) as a diagnostic biomarker in coronary heart disease (CHD) and atherosclerosis (AS)., Method: Expressions of HSP27 in patients with CHD and healthy controls were determined by enzyme-linked immunosorbent assay and the expressions of HSP27 in aortas of patients with CHD and healthy controls were measured by immunohistochemistry. Receiver operating characteristic curve was applied to assess the diagnostic performance of HSP27 in CHD. ApoE -/- mice were included and accordingly grouped. The expressions of HSP27 in AS plaque were measured by quantitative real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis. AS plaque was observed using hematoxylin and eosin staining. DHE was used to detect reactive oxygen species (ROS) levels in aortas. The expressions of mitochondrial apoptosis-related proteins were measured by Western blot analysis. Cell apoptosis was determined by TUNEL staining., Results: HSP27 was highly expressed in patients with CHD than in healthy controls ( P < 0.01). In comparison to the normal group, the model group had increased the relative positive area of HSP27 and higher expressions of HSP27, Bax, caspase-3, and apoptosis index (AI) but decreased Bcl-2 expression in AS plaque, as well as larger plaque areas and elevated ROS levels in the aorta (all P < 0.05). The HSP27-small interfering RNA group had increased expressions of Bax, caspase-3, and AI but decreased Bcl-2 and HSP27 expressions in AS plaque, as well as larger plaque areas, the relative positive area of HSP27 and higher ROS levels in aorta when compared with those in the model group (all P < 0.05)., Conclusion: HSP27 exerts its protective role by suppressing ROS and AS progression by inhibiting mitochondria apoptosis pathway in CHD., (© 2018 Wiley Periodicals, Inc.)

Introduction:: Trypanosoma cruzi (Tc) infection is usually acquired in childhood in endemic areas, leading to Chagas disease, which progresses to Chagas cardiomyopathy in 20-30% of infected individuals over decades. The pathogenesis of Chagas cardiomyopathy involves the host inflammatory response to T. cruzi, in which upstream caspase-1 activation prompts the cascade of inflammatory chemokines/cytokines, cardiac remodeling, and myocardial dysfunction. The aim of the present study was to examine the association of two caspase-1 single nucleotide polymorphisms (SNPs) with cardiomyopathy., Methods:: We recruited infected (Tc+, n = 149) and uninfected (Tc-, n = 87) participants in a hospital in Santa Cruz, Bolivia. Cardiac status was classified (I, II, III, IV) based on Chagas cardiomyopathy-associated electrocardiogram findings and ejection fractions on echocardiogram. Genotypes were determined using Taqman probes via reverse transcription-polymerase chain reaction of peripheral blood DNA. Genotype frequencies were analyzed according to three inheritance patterns (dominant, recessive, additive) using logistic regression adjusted for age and sex., Results:: The AA allele for the caspase-1 SNP rs501192 was more frequent in Tc+ cardiomyopathy (classes II, III, IV) patients compared to those with a normal cardiac status (class I) [odds ratio (OR) = -2.18, p = 0.117]. This trend approached statistical significant considering only Tc+ patients in class I and II (OR = -2.64, p = 0.064)., Conclusions:: Caspase-1 polymorphisms may play a role in Chagas cardiomyopathy development and could serve as markers to identify individuals at higher risk for priority treatment.

We evaluated the association between GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms and treatment outcomes of advanced non-small cell lung carcinoma. Between January 2010 and December 2012, a total of 244 patients with non-small cell lung carcinoma were recruited from Yiwu Central Hospital. The GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism and the results were statistically analyzed. Conditional regression analysis, showed that individuals carrying the null GSTM1 were associated with an increased risk of response to chemotherapy when compared to the present GSTM1 (odds ratio = 1.88, 95% confidence interval (CI) = 1.01-3.47). Moreover, the GG genotype of GSTP1 IIe105Val was associated with a better response to chemotherapy compared to the AA genotype (odds ratio = 2.77, 95%CI = 1.14-6.64). The null GSTM1 genotype was associated with a lower risk of death from all causes when compared with the present GSTM1 genotype (hazard ratio = 2.16, 95%CI = 1.10-4.38). Moreover, the GG genotype of GSTP1 IIe105Val was correlated with a reduced risk of death from all causes compared with the AA genotype (hazard ratio = 2.94, 95%CI = 1.11-8.68). In conclusion, we found that the null GSTM1 and the GG genotype of GSTP1 IIe105Val were correlated with a good response to chemotherapy and improved overall survival of advanced non-small cell lung carcinoma patients., Competing Interests: The authors declare no conflict of interest.

Objective: In this study, we explored the regulative effect of miR-195 on c-myb expression and also investigated the role of miR-195 and c-myb in cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) injury., Materials and Methods: QRT-PCR analysis was performed to measure mature miR-195 expression. H9c2 cells were transfected for miR-195 overexpression or knockdown or c-myb overexpression using Lipofectamine 2000. The cells were subjected to H/R treatment and following flow cytometric analysis of active caspase-3 or florescent study of reactive oxygen species (ROS) generation. The binding sites between miR-195 and 3'UTR of MYB mRNA were predicted using TargetScan 7.0. The binding sites were verified using dual luciferase assay and Western blot analysis., Results: MiR-195 is significantly upregulated after H/R treatment in H9c2 cells. H/R injury induced active caspase-3 expression. However, the cells with miR-195 suppression had substantially lower ratio of cells with active caspase-3. MiR-195 can decrease c-myb protein expression. Dual luciferase assay verified two binding sites between miR-195 and 3'UTR of MYB mRNA. C-myb overexpression can suppress mitochondrial superoxide generation and cardiomyocyte apoptosis after H/R., Conclusions: MiR-195 is significantly increased due to H/R and can enhance cardiomyocyte apoptosis. MYB is a target gene of miR-195 in cardiomyocytes. The miR-195-MYB axis is involved in regulation of cardiomyocyte apoptosis induced by H/R.

Construction of 3-vinylindoles (3) and β,β-diindolyl propionates (4) through solvent-free C-H functionalization has been explored under high-speed ball-milling conditions. The reaction selectivity is influenced by the catalyst dramatically: Pd(OAc)2 provides 3 in moderate to good yields, whereas PdX2 (X = Cl, I) affords 4 as the major products. The reaction mechanism has been further studied by using electrospray ionization mass spectrometry, implicating the dimeric palladium complex A as the key intermediate in an explanation of the selectivity.

Objective: To evaluate the efficacy of a 300 mg loading dose of clopidogrel followed by 150 mg as maintenance dose in patients with percutaneous coronary intervention (PCI)., Methods: A total of 108 consecutive patients undergoing elective PCI were recruited from our hospital from July 2007 to July 2008. A 300 mg loading dose was administered prior to PCI. Then they were randomized to receive clopidogrel 75 mg (n = 55) or 150 mg (n = 46) daily for 30 days. From Day 30 to Month 6 post-operation, all of them received 75 mg/d clopidogrel and were followed up for a mean period of 6 months., Results: Thirty days after PCI, the platelet inhibition of the 150 mg group was significantly higher than the 75 mg group (64.2% ± 13.3% vs 52.6% ± 14.3%, P = 0.00). The ratios of fatal or non-fatal myocardial infarction (MI) (1(1.8%) vs 3 (6.5%), P = 0.405) and target vessel revascularization (TVR) (4(7.2%) vs 6 (13.0%), P = 0.714) were significantly lower in the 150 mg group than those in the 75 mg group. So the overall incidence of MACE including death, MI and TVR was obviously lower in the 150 mg group than that in the 75 mg group (13.0% vs 20.2%, absolute risk reduction 7.3%)., Conclusion: A high clopidogrel maintenance dose of 150 mg daily for the first month after PCI reduces the risk of long-term adverse events in patients with elective percutaneous coronary intervention.

Objective: To observe the effect of glycoprotein receptor blockade tirofiban in acute anterior myocardial infarction patients without ST segment resolution after primary percutaneous coronary intervention (PCI)., Methods: From April 2006 to April 2008, 157 acute anterior myocardial infarction patients without ST segment resolution after PCI were randomly allocated to tirofiban (intravenous bolus 10 microg/kg followed by intravenous infusion of 0.15 microgxkg(-1)xmin(-1) for 48 h, n = 80) or equal volume saline (control group, n = 77). Baseline characteristics, PCI features and clinical outcomes during hospitalization, left ventricular ejection fractions (LVEF) and major adverse cardiac events (MACE, including death, re-infarction and target vessel revascularization) at 30 and 180 days after discharge were compared between the two groups., Results: The baseline clinical characteristics were comparable between the two groups. Compared to control group, the MACE rates and re-infarction rates at 30 days (6.3% vs.18.2%, P < 0.05; 1.3% vs.9.1%, P < 0.05, respectively) and 180 days (10.0% vs.23.4%, P < 0.05; 2.5% vs.10.4%, P < 0.05, respectively) were significantly reduced in tirofiban group. LVEF value was significantly higher in tirofiban group at 30 days and 180 days compared with those in control group [(51 +/- 6)% vs. (46 +/- 8)%, P < 0.05; (57 +/- 7)% vs. (50 +/- 9)%, P < 0.05]. Hemorrhagic complications were similar between the two groups., Conclusion: Use of tirofiban for acute anterior myocardial infarction patients without ST segment resolution after PCI is safe and can significantly improve 30 and 180 days clinical outcomes after discharge.

A miniature objective lens with a tip diameter of 1.3 mm was used for extending the penetration depth of coherent anti-Stokes Raman scattering (CARS) microscopy. Its axial and lateral focal widths were determined to be 11.4 and 0.86 microm, respectively, by two-photon excitation fluorescence imaging of 200 nm beads at a 735 nm excitation wavelength. By inserting the lens tip into a soft gel sample, CARS images of 2 microm polystyrene beads 5 mm deep from the surface were acquired. The miniature objective was applied to CARS imaging of rat spinal cord white matter with a minimal requirement for surgery.