[Clinical application of Fastpass Scorpion suture passer for arthroscopic Bankart repair].

Objective: To explore the effectiveness and advantages of using Fastpass Scorpion suture passer to stitch the inferior capsulolabral complex in arthroscopic Bankart repair compared with traditional arthroscopic suture shuttle. Methods: The clinical data of 41 patients with Bankart lesion, who met the selection criteria and were admitted between August 2019 and October 2021, was retrospectively analyzed. Under arthroscopy, the inferior capsulolabral complex was stitched with Fastpass Scorpion suture passer in 27 patients (FS group) and with arthroscopic suture shuttle in 14 patients (ASS group). There was no significant difference between the two groups ( P>0.05) in gender, age, injured side, frequency of shoulder dislocation, time from first dislocation to operation, and preoperative Rowe score of shoulder. Taking successful suture and pull-tightening as the criteria for completion of repair, the number of patients that were repaired at 5∶00 to 6∶00 (<6:00) and 6∶00 to 7∶00 positions of the glenoid in the two groups was compared. The operation time, and the difference of Rowe shoulder score betwee pre- and post-operation, the occurrence of shoulder joint dislocation, the results of apprehension test, and the constituent ratio of recovery to the pre-injury movement level between the two groups at 1 year after operation. Results: Both groups completed the repair at 5∶00 to 6∶00 (<6∶00), and the constituent ratio of patients completed at 6∶00 to 7∶00 was significantly greater in the FS group than in the ASS group ( P<0.05). The operation time was significantly shorter in the FS group than in the ASS group ( P<0.05). All incisions in the two groups healed by first intention. All patients were followed up 12-36 months (mean, 19.1 months). No anchor displacement or neurovascular injury occurred during follow-up. Rowe score of shoulder in the two groups significantly improved at 1 year after operation than preoperative scores ( P<0.05), and there was no significant difference in the difference of Rowe shoulder score between pre- and post-operation between the two groups ( P>0.05). At 1 year after operation, no re-dislocation occurred, and there was no significant difference in the apprehension test and the constituent ratio of recovery to the pre-injury movement level between the two groups ( P>0.05). Conclusion: Compared with the arthroscopic suture shuttle, using Fastpass Scorpion suture passer to stitch the inferior capsulolabral complex in arthroscopic Bankart repair is more convenient, saves operation time, and has good effectiveness.

Artificial intelligence-based recognition for variant pathogenicity of BRCA1 using AlphaFold2-predicted structures.

With the surge of the high-throughput sequencing technologies, many genetic variants have been identified in the past decade. The vast majority of these variants are defined as variants of uncertain significance (VUS), as their significance to the function or health of an organism is not known. It is urgently needed to develop intelligent models for the clinical interpretation of VUS. State-of-the-art artificial intelligence (AI)-based variant effect predictors only learn features from primary amino acid sequences, leaving out information about the most important three-dimensional structure that is more related to its function. Methods: We proposed a deep convolutional neural network model named variant effect recognition network for BRCA1 (vERnet-B) to recognize the clinical pathogenicity of missense single-nucleotide variants in the BRCT domain of BRCA1. vERnet-B learned features associated with the pathogenicity from the tertiary protein structures of variants predicted by AlphaFold2. Results: After performing a series of validation and analyses on vERnet-B, we discovered that it exhibited significant advances over previous works. Recognizing the phenotypic consequences of VUS is one of the most daunting challenges in genetic informatics; however, we achieved 85% accuracy in recognizing disease BRCA1 variants with an ideal balance of false-positive and true-positive detection rates. vERnet-B correctly recognized the pathogenicity of variant A1708E, which was poorly predicted by AlphaFold2 as previously described. The vERnet-B web server is freely available from URL: http://ai-lab.bjrz.org.cn/vERnet. Conclusions: We applied protein tertiary structures to successfully recognize the pathogenic missense SNVs, which were difficult to be addressed by classical approaches based on sequences. Our work demonstrated that AlphaFold2-predicted structures were expected to be used for rich feature learning and revealed unique insights into the clinical interpretation of VUS in disease-related genes, using vERnet-B as a discovery tool.

Association of stress hyperglycemia ratio and in-hospital mortality in patients with coronary artery disease: insights from a large cohort study.

BACKGROUND: Stress hyperglycemia is strongly associated with poor clinical outcomes in patients with acute coronary syndrome (ACS). Recently, the stress hyperglycemia ratio (SHR) has been proposed to represent relative hyperglycemia. Studies regarding the relationship between SHR and mortality in coronary artery disease (CAD) are limited. This study aimed to clarify the association between SHR and in-hospital mortality in patients with CAD. METHODS: A total of 19,929 patients with CAD who were hospitalized in Beijing Hospital were enrolled in this study. Patients with an estimated glomerular filtration rate < 30 ml/min, cancer, or missing blood glucose/HbA1c data were excluded; therefore, 8,196 patients were included in the final analysis. The patients were divided into three groups based on tertiles of SHR: T1 group (SHR < 0.725, n = 2,732), T2 group (0.725 ≤ SHR < 0.832, n = 2,730), and T3 group (SHR ≥ 0.832, n = 2,734). The primary endpoint was in-hospital mortality. RESULTS: The overall in-hospital mortality rate was 0.91% (n = 74). After adjusting for covariates, SHR was significantly associated with in-hospital mortality in patients with CAD [odds ratio (OR) = 17.038; 95% confidence interval (CI) = 9.668-30.027; P < 0.001], and the T3 group had a higher risk of in-hospital mortality (OR = 4.901; 95% CI = 2.583-9.297; P < 0.001) compared with T1 group. In the subgroup analysis, the T3 group had an increased risk of mortality among patients with pre-diabetes mellitus (pre-DM) (OR = 9.670; 95% CI = 1.886-49.571; P = 0.007) and diabetes mellitus (DM) (OR = 5.023; 95% CI = 2.371-10.640; P < 0.001) after adjustments for covariates. The relationship between SHR and in-hospital mortality among patients with ACS and chronic coronary syndrome was consistent with the main finding. SHR and in-hospital mortality exhibited a dose-response relationship, and the risk of in-hospital mortality increased when the SHR index was above 1.20. Moreover, the area under the curve of SHR for predicting in-hospital mortality in patients with CAD was 0.741. CONCLUSION: SHR is significantly associated with in-hospital mortality in patients with CAD. SHR may be an effective predictor of in-hospital mortality in patients with CAD, especially for those with pre-DM and DM.

Flattening Filter-Free Volumetric-Modulated Arc Radiotherapy for Left-Sided Whole-Breast, Partial-Breast, and Postmastectomy Irradiations.

Purpose: Unflattened photon beams exhibit many benefits over traditional flattened beams for radiotherapy (RT), but comprehensive evaluations of dosimetric results and beam-on time using flattening filter-free (FFF) beams for all types of breast irradiations are still lacking. The purpose of this study was to investigate if FFF RT can maintain equal or better dose coverage than standard flattened-beam RT while reducing doses to organs at risk (OARs) and beam-on time for various types of breast cancer irradiations. Methods and Materials: FFF volumetric-modulated arc therapy (FFF-VMAT) and standard VMAT (STD-VMAT) treatment plans were created for 15 whole-breast irradiation (WBI) patients with 50 Gy/25 fractions, 13 partial-breast irradiation (PBI) patients with 38.5 Gy/10 fractions, and 9 postmastectomy irradiation (PMI) patients with 50 Gy/25 fractions. Planning target volume (PTV) coverage and dose to OARs were evaluated. Results: Both techniques produced clinically acceptable plans for all three types of irradiations. For WBI, FFF-VMAT plans exhibited similar PTV and OARs evaluation metrics as STD-VMAT. For PBI, FFF-VMAT plans showed significantly lower mean and maximum doses for ipsilateral and contralateral lungs, contralateral breast, and heart. For PMI, FFF-VMAT plans showed significantly lower mean dose and V5 for contralateral breast but significantly higher Dmean, Dmax, and V20 for ipsilateral lung and significantly higher Dmean, V22.5, and V30 for heart. FFF-VMAT techniques significantly reduced beam-on time than STD-VMAT for all cases. Conclusion: This work has shown that FFF beams are most beneficial for small-field irradiation such as PBI, and breast cancer patients could potentially benefit from the shortened beam-on time.

Association between the triglyceride-glucose index and severity of coronary artery disease.

BACKGROUND: The triglyceride-glucose (TyG) index, which is a reliable surrogate marker of insulin resistance (IR), has been associated with cardiovascular diseases. However, evidence of the impact of the TyG index on the severity of coronary artery disease (CAD) is limited. This study investigated the relationship between the TyG index and CAD severity of individuals with different glucose metabolic statuses. METHODS: This study enrolled 2792 participants with CAD in China between January 1, 2018 and December 31, 2021. All participants were divided into groups according to the tertiles of the TyG index as follows: T1 group, TyG index < 6.87; T2 group, TyG index ≥ 6.87 to < 7.38; and T3 group, TyG index ≥ 7.38. The glucose metabolic status was classified as normal glucose regulation, pre-diabetes mellitus (pre-DM), and diabetes mellitus according to the standards of the American Diabetes Association. CAD severity was determined by the number of stenotic vessels (single-vessel CAD versus multi-vessel CAD). RESULTS: We observed a significant relationship between the TyG index and incidence of multi-vessel CAD. After adjusting for sex, age, body mass index, smoking habits, alcohol consumption, hypertension, estimated glomerular filtration rate, antiplatelet drug use, antilipidemic drug use, and antihypertensive drug use in the logistic regression model, the TyG index was still an independent risk factor for multi-vessel CAD. Additionally, the highest tertile of the TyG group (T3 group) was correlated with a 1.496-fold risk of multi-vessel CAD compared with the lowest tertile of the TyG group (T1 group) (odds ratio [OR], 1.496; 95% confidence interval [CI], 1.183-1.893; P < 0.001) in the multivariable logistic regression model. Furthermore, a dose-response relationship was observed between the TyG index and CAD severity (non-linear P = 0.314). In the subgroup analysis of different glucose metabolic statuses, the T3 group (OR, 1.541; 95% CI 1.013-2.344; P = 0.043) were associated with a significantly higher risk of multi-vessel CAD in individuals with pre-DM. CONCLUSIONS: An increased TyG index was associated with a higher risk of multi-vessel CAD. Our study indicated that TyG as an estimation index for evaluating IR could be a valuable predictor of CAD severity, especially for individuals with pre-DM.

Extracellular vesicles from bone marrow stromal cells reduce the impact of stroke on glial cell activation and blood brain-barrier permeability via a putative miR-124/PRX1 signalling pathway.

Ischaemic stroke (IS) is a cerebrovascular disease caused by cerebral infarction and cerebral artery occlusion. In this study, we proposed that EVs from bone marrow stromal cells (BMSCs) could reduce the impact of stroke by reducing the resultant glial cell activation and blood-brain barrier (BBB) leak. We furthermore investigated some of the signalling mechanisms. The transient middle cerebral artery occlusion (t-MCAO) mouse model was established. The behavioural deficits and neuronal damage were verified using Bederson's scale and the 28-point neurological score. The area of cerebral infarction was detected. The expressions of astrocytes/microglia markers and BBB permeability were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The internalization of EVs by astrocytes/microglia in the peripheral area was detected by fluorescence labelling. The expressions of astrocyte/microglia markers were measured by RT-qPCR. Levels of TNF-α and IL-1ß in microglia were detected by ELISA. BBB permeability was evaluated. The downstream target genes and pathway of miR-124 were analysed. Microglia/astrocytes were treated by oxygen-glucose deprivation reoxygenation (OGD/R). OGD/R microglia/astrocyte conditioned medium was used to culture bEnd.3 cells. The transendothelial electric resistance (TEER) of bEnd.3 cells was measured, and BBB permeability was characterized. Our results suggested that EVs from BMSCs can indeed reduce the extent of stroke-mediated damage and evidenced that these effects are mediated via expression of the non-coding RNA, miR-124 that may act via the peroxiredoxin 1 (PRX1). Our results provided further motivation to pursue the use of modified EVs as a treatment option for neurological diseases.

Magnetic covalent organic framework nanospheres-based miRNA biosensor for sensitive glioma detection.

Sensitive detection and accurate diagnosis/prognosis of glioma remain urgent challenges. Herein, dispersed magnetic covalent organic framework nanospheres (MCOF) with uniformed Fe3O4 nano-assembly as cores and high-crystalline COF as shells were prepared by monomer-mediated in-situ interface growth strategy. Based on the unique interaction between MCOF and hairpin DNA, a fluorescent signal amplified miRNA biosensor was constructed. It could realize the sensitive detection of miRNA-182 in different matrixes, where the detection limit, linearity range and determination coefficient (R2) in real blood samples reached 20 fM, 0.1 pM-10 pM and 0.991, respectively. Also, it possessed good stability and precision as observed from the low intra-day/inter-day RSD and high extraction recovery. As a result, it could quantify miRNA-182 in serum of glioma patients, the concentration of which was significantly higher than that of healthy people and obviously decreased after surgery. Finally, a proof-of-concept capillary chip system using this biosensor was proposed to realize the visualized detection of miRNA-182 in microsample. These findings suggest a robust way for sensitive detection and accurate diagnosis/prognosis of glioma.

Assessing the robustness of artificial intelligence powered planning tools in radiotherapy clinical settings-a phantom simulation approach.

BACKGROUND: Artificial intelligence (AI) based radiotherapy treatment planning tools have gained interest in automating the treatment planning process. It is essential to understand their overall robustness in various clinical scenarios. This is an existing gap between many AI based tools and their actual clinical deployment. This study works to fill the gap for AI based treatment planning by investigating a clinical robustness assessment (CRA) tool for the AI based planning methods using a phantom simulation approach. METHODS: A cylindrical phantom was created in the treatment planning system (TPS) with the axial dimension of 30 cm by 18 cm. Key structures involved in pancreas stereotactic body radiation therapy (SBRT) including PTV25, PTV33, C-Loop, stomach, bowel and liver were created within the phantom. Several simulation scenarios were created to mimic multiple scenarios of anatomical changes, including displacement, expansion, rotation and combination of three. The goal of treatment planning was to deliver 25 Gy to PTV25 and 33 Gy to PTV33 in 5 fractions in simultaneous integral boost (SIB) manner while limiting luminal organ-at-risk (OAR) max dose to be under 29 Gy. A previously developed deep learning based AI treatment planning tool for pancreas SBRT was identified as the validation object. For each scenario, the anatomy information was fed into the AI tool and the final fluence map associated to the plan was generated, which was subsequently sent to TPS for leaf sequencing and dose calculation. The final auto plan's quality was analyzed against the treatment planning constraint. The final plans' quality was further analyzed to evaluate potential correlation with anatomical changes using the Manhattan plot. RESULTS: A total of 32 scenarios were simulated in this study. For all scenarios, the mean PTV25 V25Gy of the AI based auto plans was 96.7% while mean PTV33 V33Gy was 82.2%. Large variation (16.3%) in PTV33 V33Gy was observed due to anatomical variations, a.k.a. proximity of luminal structure to PTV33. Mean max dose was 28.55, 27.68 and 24.63 Gy for C-Loop, bowel and stomach, respectively. Using D0.03cc as max dose surrogate, the value was 28.03, 27.12 and 23.84 Gy for C-Loop, bowel and stomach, respectively. Max dose constraint of 29 Gy was achieved for 81.3% cases for C-Loop and stomach, and 78.1% for bowel. Using D0.03cc as max dose surrogate, the passing rate was 90.6% for C-Loop, and 81.3% for bowel and stomach. Manhattan plot revealed high correlation between the OAR over dose and the minimal distance between the PTV33 and OAR. CONCLUSIONS: The results showed promising robustness of the pancreas SBRT AI tool, providing important evidence of its readiness for clinical implementation. The established workflow could guide the process of assuring clinical readiness of future AI based treatment planning tools.

Cost-effectiveness analysis of radiotherapy techniques for whole breast irradiation.

BACKGROUND: The current standard of care (SOC) for whole breast radiotherapy (WBRT) in the US is conventional tangential photon fields. Advanced WBRT techniques may provide similar tumor control and better normal tissue sparing, but it is controversial whether the medical benefits of an advanced technology are significant enough to justify its higher cost. OBJECTIVE: To analyze the cost-effectiveness of six advanced WBRT techniques compared with SOC. METHODS: We developed a Markov model to simulate health states for one cohort of women (65-year-old) with early-stage breast cancer over 15 years after WBRT. The cost effectiveness analyses of field-in-field (FIF), hybrid intensity modulated radiotherapy (IMRT), full IMRT, standard volumetric modulated arc therapy (STD-VMAT), multiple arc VMAT (MA-VMAT), non-coplanar VMAT (NC-VMAT) compared with SOC were performed with both tumor control and radiogenic side effects considered. Transition probabilities and utilities for each health state were obtained from literature. Costs incurred by payers were adopted from literature and Medicare data. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. One-way sensitivity analyses and probabilistic sensitivity analyses (PSA) were performed to evaluate the impact of uncertainties on the final results. RESULTS: FIF has the lowest ICER value of 1,511 $/QALY. The one-way analyses show that the cost-effectiveness of advanced WBRT techniques is most sensitive to the probability of developing contralateral breast cancer. PSAs show that SOC is more cost effective than almost all advanced WBRT techniques at a willingness-to-pay (WTP) threshold of 50,000 $/QALY, while FIF, hybrid IMRT and MA-VMAT are more cost-effective than SOC with a probability of 59.2%, 72.3% and 72.6% at a WTP threshold of 100,000 $/QALY, respectively. CONCLUSIONS: FIF might be the most cost-effective option for WBRT patients at a WTP threshold of 50,000 $/QALY, while hybrid IMRT and MA-VMAT might be the most cost-effective options at a WTP threshold of 100,000 $/QALY.

Versatile hollow COF nanospheres via manipulating transferrin corona for precise glioma-targeted drug delivery.

Covalent organic framework (COF) nanoparticles for interference-free targeted drug delivery to glioma remains in its infancy. Herein, hollow COF nanospheres with high crystallinity and uniformed sizes were facilely prepared via heterogeneous nucleation-growth. The prepared COF had large surface area/pore volume and exhibited appropriate degradation behavior under acid environment, where therefore doxorubicin was effectively encapsulated and exhibited a pH-sensitive release. Most charmingly, T10 peptide that has high affinity with transferrin (Tf), was conjugated to endow the hollow COF interesting properties to specifically absorb Tf in vivo as Tf corona. For the first time, multifunctional hollow COF nanospheres (the better one named DCPT-2) were successfully synthesized to achieve interference-free cascade-targeting glioma drug delivery across the blood-brain barrier. Treatment with DCPT-2 brought an improved therapeutic outcome with significantly prolonged median survival time and low side effects. This work promised not only a potential protein corona-mediated COF-based drug delivery platform with good biocompatibility for effective and precise brain tumor therapy, but also an endogenous protein corona-mediated targeting strategy for general cancer therapy.

Cost-effectiveness analysis of advanced radiotherapy techniques for post-mastectomy breast cancer patients.

BACKGROUND: Prior cost-effectiveness studies of post-mastectomy radiotherapy (PMRT) only compared conventional radiotherapy versus no radiotherapy and only considered tumor control. The goal of this study was to perform cost-effectiveness analyses of standard of care (SOC) and advanced PMRT techniques including intensity-modulated radiotherapy (IMRT), standard volumetric modulated arc therapy (STD-VMAT), non-coplanar VMAT (NC-VMAT), multiple arc VMAT (MA-VMAT), Tomotherapy (TOMO), mixed beam therapy (MIXED), and intensity-modulated proton therapy (IMPT). METHODS: Using a Markov model, we estimated the cost-effectiveness of various techniques over 15 years. A cohort of women (55-year-old) was simulated in the model, and radiogenic side effects were considered. Transition probabilities, utilities, and costs for each health state were obtained from literature and Medicare data. Model outcomes include quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). RESULTS: For the patient cohort, STD-VMAT has an ICER of $32,617/QALY relative to SOC; TOMO is dominated by STD-VMAT; IMRT has an ICER of $19,081/QALY relative to STD-VMAT; NC-VMAT, MA-VMAT, MIXED are dominated by IMRT; IMPT has an ICER of $151,741/QALY relative to IMRT. One-way analysis shows that the probability of cardiac toxicity has the most significant impact on the model outcomes. The probability sensitivity analyses show that all advanced PMRT techniques are more cost-effective than SOC at a willingness-to-pay (WTP) threshold of $100,000/QALY, while almost none of the advanced techniques is more cost-effective than SOC at a WTP threshold of $50,000/QALY. CONCLUSION: Advanced PMRT techniques are more cost-effective for breast cancer patients at a WTP threshold of $100,000/QALY, and IMRT might be a cost-effective option for PMRT patients.

Comparison of conventional and advanced radiotherapy techniques for left-sided breast cancer after breast conserving surgery.

Whole breast radiotherapy (WBRT) after breast conserving surgery is the standard treatment to prevent recurrence and metastasis of early stage breast cancer. This study aims to compare seven WBRT techniques including conventional tangential, field-in-field (FIF), hybrid intensity-modulated radiotherapy (IMRT), IMRT, standard volumetric modulated arc therapy (STD-VMAT), noncoplanar VMAT (NC-VMAT), and multiple arc VMAT (MA-VMAT). Fifteen patients who were previously diagnosed with left-sided early stage breast cancer and treated in our clinic were selected for this study. WBRT plans were created for these patients and were evaluated based on target coverage and normal tissue toxicities. All techniques produced clinically acceptable WBRT plans. STD-VMAT delivered the lowest mean dose (1.1 ± 0.3 Gy) and the lowest maximum dose (7.3 ± 4.9 Gy) to contralateral breast, and the second lowest lifetime attributable risk (LAR) (4.1 ± 1.4%) of secondary contralateral breast cancer. MA-VMAT delivered the lowest mean dose to lungs (4.9 ± 0.9 Gy) and heart (5.5 ± 1.2 Gy), exhibited the lowest LAR (1.7 ± 0.3%) of secondary lung cancer, normal tissue complication probability (NTCP) (1.2 ± 0.2%) of pneumonitis, risk of coronary events (RCE) (10.3 ± 2.7%), and LAR (3.9 ± 1.3%) of secondary contralateral breast cancer. NC-VMAT plans provided the most conformal target coverage, the lowest maximum lung dose (46.2 ± 4.1 Gy) and heart dose (41.1 ± 5.4 Gy), and the second lowest LAR (1.8 ± 0.4%) of secondary lung cancer and RCE (10.5 ± 2.8%). MA-VMAT and NC-VMAT could be the preferred techniques for early stage breast cancer patients after breast conserving surgery.

Postmastectomy radiotherapy for left-sided breast cancer patients: Comparison of advanced techniques.

Postmastectomy radiotherapy (PMRT) has been shown to improve the overall survival for invasive breast cancer patients, and many advanced radiotherapy technologies were adopted for PMRT. The purpose of our study is to compare various advanced PMRT techniques including fixed-beam intensity-modulated radiotherapy (IMRT), non-coplanar volumetric modulated arc therapy (NC-VMAT), multiple arc VMAT (MA-VMAT), and tomotherapy (TOMO). Results of standard VMAT and mixed beam therapy that were published by our group previously were also included in the plan comparisons. Treatment plans were produced for nine PMRT patients previously treated in our clinic. The plans were evaluated based on planning target volume (PTV) coverage, dose homogeneity index (DHI), conformity index (CI), dose to organs at risk (OARs), normal tissue complication probability (NTCP) of pneumonitis, lifetime attributable risk (LAR) of second cancers, and risk of coronary events (RCE). All techniques produced clinically acceptable PMRT plans. Overall, fixed-beam IMRT delivered the lowest mean dose to contralateral breast (1.56 ± 0.4 Gy) and exhibited lowest LAR (0.6 ± 0.2%) of secondary contralateral breast cancer; NC-VMAT delivered the lowest mean dose to lungs (7.5 ± 0.8 Gy), exhibited lowest LAR (5.4 ± 2.8%) of secondary lung cancer and lowest NTCP (2.1 ± 0.4%) of pneumonitis; mixed beam therapy delivered the lowest mean dose to heart (7.1 ± 1.3 Gy) and exhibited lowest RCE (8.6 ± 7.1%); TOMO plans provided the most optimal target coverage while delivering higher dose to OARs than other techniques. Both NC-VMAT and MA-VMAT exhibited lower values of all OARs evaluation metrics compare to standard VMAT. Fixed-beam IMRT, NC-VMAT, and mixed beam therapy could be the optimal radiation technique for certain breast cancer patients after mastectomy.

Evodialones A and B: Polyprenylated Acylcyclopentanone Racemates with a 3-Ethyl-1,1-diisopentyl-4-methylcyclopentane Skeleton from Evodia lepta.

Two polyprenylated acylcyclopentanone racemates, evodialones A (1) and B (2), featuring a 3-ethyl-1,1-diisopentyl-4-methylcyclopentane skeleton, were isolated from an extract of the aerial parts of Evodia lepta. Evodialone A (1) was resolved by chiral-phase HPLC to afford a pair of enantiomers, (+)- and (-)-evodialones A (1b/1a), while evodialone B (2) could not be resolved. Their structures were elucidated by spectroscopic analysis and a combination of computational techniques including gauge-independent atomic orbital calculation of 1D NMR data and experimental and TDDFT-calculated ECD spectra. A putative biosynthetic pathway of 1 and 2 starting from the monocyclic polyprenylated acylphloroglucinols is proposed. All the isolates were screened for the antimicrobial activity in vitro, and 1a and 1b showed moderate inhibitory activities against several pathogenic fungi with MICs values of 17.1-68.3 µM.

Modeling of the metallic port in breast tissue expanders for photon radiotherapy.

The purpose of this study was to model the metallic port in breast tissue expanders and to improve the accuracy of dose calculations in a commercial photon treatment planning system (TPS). The density of the model was determined by comparing TPS calculations and ion chamber (IC) measurements. The model was further validated and compared with two widely used clinical models by using a simplified anthropomorphic phantom and thermoluminescent dosimeters (TLD) measurements. Dose perturbations and target coverage for a single postmastectomy radiotherapy (PMRT) patient were also evaluated. The dimensions of the metallic port model were determined to be 1.75 cm in diameter and 5 mm in thickness. The density of the port was adjusted to be 7.5 g/cm3 which minimized the differences between IC measurements and TPS calculations. Using the simplified anthropomorphic phantom, we found the TPS calculated point doses based on the new model were in agreement with TLD measurements within 5.0% and were more accurate than doses calculated based on the clinical models. Based on the photon treatment plans for a real patient, we found that the metallic port has a negligible dosimetric impact on chest wall, while the port introduced significant dose shadow in skin area. The current clinical port models either overestimate or underestimate the attenuation from the metallic port, and the dose perturbation depends on the plan and the model in a complex way. TPS calculations based on our model of the metallic port showed good agreement with measurements for all cases. This new model could improve the accuracy of dose calculations for PMRT patients who have temporary tissue expanders implanted during radiotherapy and could potentially reduce the risk of complications after the treatment.

Evaluation of surface and shallow depth dose reductions using a Superflab bolus during conventional and advanced external beam radiotherapy.

The purpose of this study was to evaluate a methodology to reduce scatter and leakage radiations to patients' surface and shallow depths during conventional and advanced external beam radiotherapy. Superflab boluses of different thicknesses were placed on top of a stack of solid water phantoms, and the bolus effect on surface and shallow depth doses for both open and intensity-modulated radiotherapy (IMRT) beams was evaluated using thermoluminescent dosimeters and ion chamber measurements. Contralateral breast dose reduction caused by the bolus was evaluated by delivering clinical postmastectomy radiotherapy (PMRT) plans to an anthropomorphic phantom. For the solid water phantom measurements, surface dose reduction caused by the Superflab bolus was achieved only in out-of-field area and on the incident side of the beam, and the dose reduction increased with bolus thickness. The dose reduction caused by the bolus was more significant at closer distances from the beam. Most of the dose reductions occurred in the first 2-cm depth and stopped at 4-cm depth. For clinical PMRT treatment plans, surface dose reductions using a 1-cm Superflab bolus were up to 31% and 62% for volumetric-modulated arc therapy and 4-field IMRT, respectively, but there was no dose reduction for Tomotherapy. A Superflab bolus can be used to reduce surface and shallow depth doses during external beam radiotherapy when it is placed out of the beam and on the incident side of the beam. Although we only validated this dose reduction strategy for PMRT treatments, it is applicable to any external beam radiotherapy and can potentially reduce patients' risk of developing radiation-induced side effects.

Label-free, Water-soluble Fluorescent Peptide Probe for a Sensitive and Selective Determination of Copper Ions.

This study aimed to develop a label-free, sensitive, selective, and environment-friendly fluorescent peptide probe His-His-Trp-His (HHWH) for determining the concentration of copper ion (Cu2+) in aqueous solutions. The results demonstrated that the designed HHWH has a high selectivity and sensitivity for monitoring the concentration of free Cu2+ via quenching of the probe fluorescence upon a binding of Cu2+. The fluorescence intensity of the HHWH had a linear relationship with the concentration of Cu2+ between 10 nM and 10 µM, and the detection limit was 8 nM. Furthermore, HHWH could be regenerated with sulfide ions at least five times. The concentrations of Cu2+ in three different real water samples were detected using this probe, and the results were consistent with the one detected using an atomic absorption spectrometer. Thus, HHWH can be used as an accurate and feasible fluorescent peptide probe for detecting Cu2+ in aqueous solutions.

[Different surgical methods for treatment of senile osteoporotic comminuted proximal humerus fracture].

OBJECTIVE: To compare the efficacy and indication of the three different surgical methods in the treatment of the senile osteoporotic comminuted proximal humerus fracture. METHODS: From January 2006 to April 2008, 70 senile patients with osteoporotic comminuted proximal humerus fracture were randomly divided into three groups to receive different surgical methods. There were 21 patients in the group A receiving Kirschner tension band or screw internal fixation, 37 patients in group B receiving internal fixation of locking proximal humeral plate, and 12 patients in group C receiving humeral head replacement. There were 36 males and 34 females aged 53-76 years old (average 61.9 years old). All the fractures were closed, osteoporotic, and III and IV-part according to Neer classification. The disease course was 1-8 days (average 2.8 days). There was no significant difference among three groups in terms of baseline information (P > 0.05). The effective anti-osteoporosis therapy was given during perioperative period. RESULTS: All the incision healed by first intention. All patients reached anatomical or almost anatomical reduction without complications such as postoperative infection, neurovascular injury, and nonunion of bone. Seventy patients were followed up for 9-20 months (average 11.5 months). The healing time of the fracture was 8-12 weeks in group A and group B, the average healing time was 10.5 weeks in group A and 10 weeks in group B, and there was no significant difference between two groups (P > 0.05). Group C presented with no sign of prosthesis loosening or shoulder dislocation. Six cases in group A suffered from frozen shoulder, pain or acromion impingement syndrome 6 months after operation and obtained various degrees of improvement via functional exercises. One of them had humeral head avascular necrosis 12 months later and achieved fair recovery after performing humeral head replacement. Two cases in group B had frozen and painful shoulder 6 months after operation and achieved fair recovery after functional exercises. One cases in group C had frozen shoulder and poor performance of abduction and uplifting and achieved improvement after exercises. The rest patients achieved satisfactory curative effects. The incidence of complication was 28.6% in group A, 5.4% in group B, and 8.3% in group C. The incidence of complication in group A was significantly higher than that of group B and group C (P < 0.05), and there was no significant difference between group B and group C (P > 0.05). Neer scale system was adopted to evaluate the postoperative shoulder function, the excellent and good rate was 66.7% in group A, 78.4% in group B, and 83.3% in group C. The excellent and good rate in group A was significantly less than that of group B and group C (P < 0.05), and there was no significant difference between group B and group C (P > 0.05). CONCLUSION: The senile osteoporotic comminuted proximal humerus fracture treated by surgery can obtain satisfied results. Most patients can use locking plate fixation. Those with poor general condition can use Kirschner wire fixation with tension band or screws, but this method is subject to certain constraints. For some elder patients with humeral head necrosis and humeral head crushed, priority should be given to the use of humeral head replacement.

[Applied anatomy study and clinical application of great saphenous veno-saphenous neurocutaneous vascular flap].

OBJECTIVE: To provide the anatomic basis for defect repair of the knee, leg, foot and ankle with great saphenous veno-saphenous neurocutaneous vascular island flaps. METHODS: The origin, diameter, branches, distribution and anastomoses of the saphenous artery and saphenous neurocutaneous vascular were observed on 20 sides of adult leg specimens and 4 fresh cadaver voluntary legs. Another 4 fresh cadaver voluntary legs were radiographed with a soft X-ray system after the intravenous injection of Vermilion and cross-sections under profound fascial, other hand, micro-anatomic examination was also performed in these 4 fresh cadaver legs. The soft tissue defects in lower extremity, upper extremity, heel or Hucou in hand were repaired with the proximal or distal pedicle flaps or free flaps in 18 patients (12 males and 6 females,aging from 7 to 53 years). The defect was caused by trauma, tumour, ulcer and scar. The locations were Hucou (1 case), upper leg (3 cases), lower extremity and heal (14 cases). Of then, 7 cases were complicated by bone exposure, 3 cases by tendon exposure and 1 case by steel espouse, the defect size were 4 cm x 4 cm to 7 cm x 13 cm. The flap sizes were 4 cm x 6 cm to 8 cm x 15 cm, which pedicle length was 8-11 cm with 2.5-4.0 cm fascia and 1-2 cm skin at width. RESULTS: Genus descending genicular artery began from 9.33 +/- 0.81 cm away from upper the condyles medialis, it branched saphenous artery accompanying saphenous nerve descendent. And saphenous artery reached the surface of the skin 7.21 +/- 0.82 cm away from lower the condyles medialis, and anastomosed with the branches of tibialis posterior artery, like "Y" or "T" pattern. The chain linking system of arteries were found accompanying along the great saphenous vein as saphenous nerve, and then a axis blood vessel was formed. The small artery of only 0.05-0.10 mm in diameter, distributed around the great saphenous vein within 5-8 mm and arranged parallelly along the vein like water wave in soft X-ray film. All proximal flaps, distal pedicle flaps and free flaps survived well. The appearance, sensation and function were satisfactory in 14 patients after a follow-up of 6-12 months. CONCLUSION: The great saphenous vein as well as saphenous neurocutaneous has a chain linking system vascular net. A flap with the vascular net can be transplanted by free, by reversed pedicle, or by direct pedicle to repair the wound of upper leg and foot. A superficial vein-superficial neurocutaneous vascular flap with abundance blood supply and without sacrificing a main artery is a favourite method in repair of soft tissue defects in foot and lower extremity.