Quality of life in young patients with acute type a aortic dissection in China: comparison with Marfan syndrome and non-Marfan syndrome.

BACKGROUND: There is a paucity of Chinese studies evaluating the quality of life (QoL) in young acute type A aortic dissection (AAAD) patients with Marfan syndrome. METHODS: Young adult AAAD patients (younger than 45 years old) underwent surgical treatment at our institution from January 2017 to December 2020 were consecutive enrolled. The hospital survivors completed 1 year of follow up. Patients were divided into two groups according to the presence or absence of Marfan syndrome (MFS). A 1:1 propensity score matching (PSM) with a caliper 0.2 was conducted to balance potential bias in baseline. The follow-up data were analyzed primarily for change in quality of life and anxiety status. RESULTS: After PSM, 32 comparable pairs were matched. The baseline data were comparable and postoperative complications were similar between groups. In terms of SF-36 scale, the role physical, bodily pain, role emotional and mental health subscales were no significantly improved in MFS patients over time. At 1 year after discharged, the subscale of mental health and bodily pain were significantly lower in the MFS group than in the non-MFS group. In terms of HADS assessments, the level of anxiety in MFS patients was significantly higher than in non-MFS patients at 1 year after discharged. CONCLUSIONS: The QoL in young AAAD patients with MFS is lower than those without MFS after surgery. This may be associated with the uncontrollable persistent chronic pain and the uncertainty and concerns for the disease's progression.

Left ventricular recovery after total arterial coronary artery bypass grafting versus conventional coronary artery bypass grafting in patients with multivessel coronary artery disease and reduced left ventricular ejection fraction.

BACKGROUND: We compared total arterial revascularization (TAR) versus conventional revascularization (CR) in terms of left ventricular function recovery in patients with multivessel coronary artery disease (CAD) and reduced left ventricular ejection fraction (LVEF). METHODS: We conducted a retrospective cohort study of 162 consecutive patients with multivessel CAD and reduced LVEF who underwent isolated coronary artery bypass grafting at our institution between January 2013 and July 2022. We assessed left ventricular function by transthoracic echocardiography at admission, before discharge, and at follow-up of 3, 6, and 12 months, using LVEF, global longitudinal peak strain, end-diastolic volume index, and end-systolic volume index. We also evaluated mitral valve regurgitation and graft patency rate at 1 year. RESULTS: The TAR group had a significantly higher increase in LVEF and global longitudinal peak strain, and a significantly lower decrease in end-diastolic volume index and end-systolic volume index than the CR group at 6 and 12 months after surgery. The TAR group also had a significantly lower degree of mitral valve regurgitation than the CR group at all-time points within 12 months after surgery. The TAR group had a significantly higher graft patency rate than the CR group at 12 months. There was no significant difference in hospital mortality or repeat revascularization between the groups. CONCLUSIONS: TAR was associated with better recovery of left ventricular function than CR in patients with multivessel CAD and reduced LVEF. Further studies are needed to confirm these findings in this high-risk population.

PD-L1 upregulation promotes drug-induced pulmonary fibrosis by inhibiting vimentin degradation.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality and limited therapeutic options. The immune checkpoint PD1/PD-L1 axis is related to the pathogenesis of pulmonary fibrosis, and upregulated expression levels of PD-L1 have been demonstrated in IPF patients. However, the mechanism of PD-L1 in pulmonary fibrosis is not fully understood. Here, we demonstrated upregulated expression of PD-L1 in fibrotic lung tissues and sera of IPF patients. Bleomycin (BLM) treatment induced PD-L1 upregulation, EMT (Epithelial-Mesenchymal Transition) and fibrosis-like morphology changes in human pulmonary alveolar epithelial cells (HPAEpiCs). Silencing PD-L1 attenuated BLM-induced EMT and fibrosis-like morphology changes in HPAEpiCs. In addition, we identified that PD-L1 directly binds to vimentin and inhibits vimentin ubiquitination, thereby increasing vimentin levels in HPAEpiCs. Silencing of vimentin inhibited BLM- and PD-L1-induced fibrosis in HPAEpiCs. The correlation between PD-L1 and EMT or vimentin expression was further confirmed in clinical samples and animal models. Finally, we used BLM- and paraquat-induced pulmonary fibrosis animal models to confirm the anti-pulmonary fibrosis effects of PD-L1 silencing. Taken together, our findings suggest that upregulated PD-L1 stimulates EMT of alveolar epithelial cells by increasing vimentin levels by inhibiting vimentin ubiquitination, thereby contributing to pulmonary fibrosis.

Does the Presence of Missing Data Affect the Performance of the SORG Machine-learning Algorithm for Patients With Spinal Metastasis? Development of an Internet Application Algorithm.

BACKGROUND: The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA) was developed to predict the survival of patients with spinal metastasis. The algorithm was successfully tested in five international institutions using 1101 patients from different continents. The incorporation of 18 prognostic factors strengthens its predictive ability but limits its clinical utility because some prognostic factors might not be clinically available when a clinician wishes to make a prediction. QUESTIONS/PURPOSES: We performed this study to (1) evaluate the SORG-MLA's performance with data and (2) develop an internet-based application to impute the missing data. METHODS: A total of 2768 patients were included in this study. The data of 617 patients who were treated surgically were intentionally erased, and the data of the other 2151 patients who were treated with radiotherapy and medical treatment were used to impute the artificially missing data. Compared with those who were treated nonsurgically, patients undergoing surgery were younger (median 59 years [IQR 51 to 67 years] versus median 62 years [IQR 53 to 71 years]) and had a higher proportion of patients with at least three spinal metastatic levels (77% [474 of 617] versus 72% [1547 of 2151]), more neurologic deficit (normal American Spinal Injury Association [E] 68% [301 of 443] versus 79% [1227 of 1561]), higher BMI (23 kg/m2 [IQR 20 to 25 kg/m2] versus 22 kg/m2 [IQR 20 to 25 kg/m2]), higher platelet count (240 × 103/µL [IQR 173 to 327 × 103/µL] versus 227 × 103/µL [IQR 165 to 302 × 103/µL], higher lymphocyte count (15 × 103/µL [IQR 9 to 21× 103/µL] versus 14 × 103/µL [IQR 8 to 21 × 103/µL]), lower serum creatinine level (0.7 mg/dL [IQR 0.6 to 0.9 mg/dL] versus 0.8 mg/dL [IQR 0.6 to 1.0 mg/dL]), less previous systemic therapy (19% [115 of 617] versus 24% [526 of 2151]), fewer Charlson comorbidities other than cancer (28% [170 of 617] versus 36% [770 of 2151]), and longer median survival. The two patient groups did not differ in other regards. These findings aligned with our institutional philosophy of selecting patients for surgical intervention based on their level of favorable prognostic factors such as BMI or lymphocyte counts and lower levels of unfavorable prognostic factors such as white blood cell counts or serum creatinine level, as well as the degree of spinal instability and severity of neurologic deficits. This approach aims to identify patients with better survival outcomes and prioritize their surgical intervention accordingly. Seven factors (serum albumin and alkaline phosphatase levels, international normalized ratio, lymphocyte and neutrophil counts, and the presence of visceral or brain metastases) were considered possible missing items based on five previous validation studies and clinical experience. Artificially missing data were imputed using the missForest imputation technique, which was previously applied and successfully tested to fit the SORG-MLA in validation studies. Discrimination, calibration, overall performance, and decision curve analysis were applied to evaluate the SORG-MLA's performance. The discrimination ability was measured with an area under the receiver operating characteristic curve. It ranges from 0.5 to 1.0, with 0.5 indicating the worst discrimination and 1.0 indicating perfect discrimination. An area under the curve of 0.7 is considered clinically acceptable discrimination. Calibration refers to the agreement between the predicted outcomes and actual outcomes. An ideal calibration model will yield predicted survival rates that are congruent with the observed survival rates. The Brier score measures the squared difference between the actual outcome and predicted probability, which captures calibration and discrimination ability simultaneously. A Brier score of 0 indicates perfect prediction, whereas a Brier score of 1 indicates the poorest prediction. A decision curve analysis was performed for the 6-week, 90-day, and 1-year prediction models to evaluate their net benefit across different threshold probabilities. Using the results from our analysis, we developed an internet-based application that facilitates real-time data imputation for clinical decision-making at the point of care. This tool allows healthcare professionals to efficiently and effectively address missing data, ensuring that patient care remains optimal at all times. RESULTS: Generally, the SORG-MLA demonstrated good discriminatory ability, with areas under the curve greater than 0.7 in most cases, and good overall performance, with up to 25% improvement in Brier scores in the presence of one to three missing items. The only exceptions were albumin level and lymphocyte count, because the SORG-MLA's performance was reduced when these two items were missing, indicating that the SORG-MLA might be unreliable without these values. The model tended to underestimate the patient survival rate. As the number of missing items increased, the model's discriminatory ability was progressively impaired, and a marked underestimation of patient survival rates was observed. Specifically, when three items were missing, the number of actual survivors was up to 1.3 times greater than the number of expected survivors, while only 10% discrepancy was observed when only one item was missing. When either two or three items were omitted, the decision curves exhibited substantial overlap, indicating a lack of consistent disparities in performance. This finding suggests that the SORG-MLA consistently generates accurate predictions, regardless of the two or three items that are omitted. We developed an internet application (https://sorg-spine-mets-missing-data-imputation.azurewebsites.net/) that allows the use of SORG-MLA with up to three missing items. CONCLUSION: The SORG-MLA generally performed well in the presence of one to three missing items, except for serum albumin level and lymphocyte count (which are essential for adequate predictions, even using our modified version of the SORG-MLA). We recommend that future studies should develop prediction models that allow for their use when there are missing data, or provide a means to impute those missing data, because some data are not available at the time a clinical decision must be made. CLINICAL RELEVANCE: The results suggested the algorithm could be helpful when a radiologic evaluation owing to a lengthy waiting period cannot be performed in time, especially in situations when an early operation could be beneficial. It could help orthopaedic surgeons to decide whether to intervene palliatively or extensively, even when the surgical indication is clear.

SM22α Deletion Contributes to Neurocognitive Impairment in Mice through Modulating Vascular Smooth Muscle Cell Phenotypes.

Considerable evidence now indicates that cognitive impairment is primarily a vascular disorder. The depletion of smooth muscle 22 alpha (SM22α) contributes to vascular smooth muscle cells (VSMCs) switching from contractile to synthetic and proinflammatory phenotypes in the context of inflammation. However, the role of VSMCs in the pathogenesis of cognitive impairment remains undetermined. Herein, we showed a possible link between VSMC phenotypic switching and neurodegenerative diseases via the integration of multi-omics data. SM22α knockout (Sm22α-/-) mice exhibited obvious cognitive impairment and cerebral pathological changes, which were visibly ameliorated by the administration of AAV-SM22α. Finally, we confirmed that SM22α disruption promotes the expression of SRY-related HMG-box gene 10 (Sox10) in VSMCs, thereby aggravating the systemic vascular inflammatory response and ultimately leading to cognitive impairment in the brain. Therefore, this study supports the idea of VSMCs and SM22α as promising therapeutic targets in cognitive impairment to improve memory and cognitive decline.

Morphological, transcriptomic and metabolomic analyses of Sophora davidii mutants for plant height.

Sophora davidii is an important plant resource in the karst region of Southwest China, but S. davidii plant-height mutants are rarely reported. Therefore, we performed phenotypic, anatomic structural, transcriptomic and metabolomic analyses to study the mechanisms responsible for S. davidii plant-height mutants. Phenotypic and anatomical observations showed that compared to the wild type, the dwarf mutant displayed a significant decrease in plant height, while the tall mutant displayed a significant increase in plant height. The dwarf mutant cells were smaller and more densely arranged, while those of the wild type and the tall mutant were larger and loosely arranged. Transcriptomic analysis revealed that differentially expressed genes (DEGs) involved in cell wall biosynthesis, expansion, phytohormone biosynthesis, signal transduction pathways, flavonoid biosynthesis and phenylpropanoid biosynthesis were significantly enriched in the S. davidii plant-height mutants. Metabolomic analysis revealed 57 significantly differential metabolites screened from both the dwarf and tall mutants. A total of 8 significantly different flavonoid compounds were annotated to LIPID MAPS, and three metabolites (chlorogenic acid, kaempferol and scopoletin) were involved in phenylpropanoid biosynthesis and flavonoid biosynthesis. These results shed light on the molecular mechanisms of plant height in S. davidii mutants and provide insight for further molecular breeding programs.

Drug repurposing against breast cancer by integrating drug-exposure expression profiles and drug-drug links based on graph neural network.

MOTIVATION: Breast cancer is one of the leading causes of cancer deaths among women worldwide. It is necessary to develop new breast cancer drugs because of the shortcomings of existing therapies. The traditional discovery process is time-consuming and expensive. Repositioning of clinically approved drugs has emerged as a novel approach for breast cancer therapy. However, serendipitous or experiential repurposing cannot be used as a routine method. RESULTS: In this study, we proposed a graph neural network model GraphRepur based on GraphSAGE for drug repurposing against breast cancer. GraphRepur integrated two major classes of computational methods, drug network-based and drug signature-based. The differentially expressed genes of disease, drug-exposure gene expression data and the drug-drug links information were collected. By extracting the drug signatures and topological structure information contained in the drug relationships, GraphRepur can predict new drugs for breast cancer, outperforming previous state-of-the-art approaches and some classic machine learning methods. The high-ranked drugs have indeed been reported as new uses for breast cancer treatment recently. AVAILABILITYAND IMPLEMENTATION: The source code of our model and datasets are available at: https://github.com/cckamy/GraphRepur and https://figshare.com/articles/software/GraphRepur_Breast_Cancer_Drug_Repurposing/14220050. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Do Polystyrene Nanoplastics Have Similar Effects on Duckweed (Lemna minor L.) at Environmentally Relevant and Observed-Effect Concentrations?

Although the biological effects of nanoplastics (<100 nm in size) in aquatic environments have been increasingly investigated, almost all such studies have been performed at observed-effect concentrations (higher than 1 µg/mL). The use of observed-effect concentrations of nanoplastics can provide essential data for evaluating the potential risks, but how these results apply to the effects of concentrations of nanoplastics observed in the environment remains unclear. Here, we show that exposure to both positively and negatively charged nanoplastics at the observed-effect concentration (ranging from 0 to 50 µg/mL) can result in physiological changes of Lemna minor L., a typical flowering aquatic plant species, inducing H2O2 and O2- accumulation and even cell death. However, the nanoplastics at environmentally relevant concentrations (lower than 0.1 µg/mL) had no obvious effects on phenotype of L. minor. Moreover, nanoplastics at both observed-effect and environmentally relevant concentrations were adsorbed onto the roots and fronds of the plants, whereas uptake by the roots and fronds occurred only at the observed-effect concentration. Although no phenotypic changes across 30 generations of cultivation were observed when the plants were exposed to 0.015 µg/mL nanoplastics, the expression of genes related to the response to stimuli and to oxidative and osmotic stress was upregulated under both observed-effect and environmentally relevant concentrations. Our findings suggest that the long-term presence of nanoplastics at environmentally relevant concentrations might induce some variations in the transcription level and have potential threat to floating microphytes and aquatic ecosystems.

Early Clinical Outcomes of Thoracoscopic Mitral Valvuloplasty: The First 90 Cases.

BACKGROUND: We reported 90 cases of thoracoscopic mitral valvuloplasty in its early stages and sought to analyze early clinical outcomes. METHODS: Ninety consecutive patients, who underwent thoracoscopic mitral valvuloplasty at our institute between April 2020 and December 2021, were assessed for outcomes. Clinical data, including baseline characteristics, operative data, postoperative data, and early follow-up results, were collected. The early clinical outcomes were used to assess the reliability and efficiency of this technique. RESULTS: No in-hospital death occurred. One patient underwent a median sternotomy for bleeding. Intraoperative transesophageal echocardiography revealed no mitral regurgitation in 82 patients and mitral regurgitation of 0-2 cm2 in six. The remaining two patients with mitral regurgitation >2 cm2 experienced serious systolic anterior motion but underwent successful re-valvuloplasty during a second pump-up. the mean cardiopulmonary bypass time was 177.1±54.8 min and aortic clamping time, 114.0±44.9 min. Each patient received a prosthetic ring (CG Future™), and 64 patients received artificial chordae with an average of 2.7±1.5 (ranging from 1 to 6) pairs. The mean follow up was 8.8±7.0 (range, 1-22 months), while two patients were lost to follow up. Recurrent severe mitral regurgitation was observed in one patient three months after the operation, and mitral valve replacement was performed via median sternotomy. During follow up, one patient died of upper respiratory tract infection, and one suffered from low cardiac output. CONCLUSIONS: Thoracoscopic mitral valvuloplasty is safe and effective and, once surgeons overcome the learning curve, can achieve excellent early clinical outcomes.

Helmet Wearing State Detection Based on Improved Yolov5s.

At many construction sites, whether to wear a helmet is directly related to the safety of the workers. Therefore, the detection of helmet use has become a crucial monitoring tool for construction safety. However, most of the current helmet wearing detection algorithms are only dedicated to distinguishing pedestrians who wear helmets from those who do not. In order to further enrich the detection in construction scenes, this paper builds a dataset with six cases: not wearing a helmet, wearing a helmet, just wearing a hat, having a helmet, but not wearing it, wearing a helmet correctly, and wearing a helmet without wearing the chin strap. On this basis, this paper proposes a practical algorithm for detecting helmet wearing states based on the improved YOLOv5s algorithm. Firstly, according to the characteristics of the label of the dataset constructed by us, the K-means method is used to redesign the size of the prior box and match it to the corresponding feature layer to increase the accuracy of the feature extraction of the model; secondly, an additional layer is added to the algorithm to improve the ability of the model to recognize small targets; finally, the attention mechanism is introduced in the algorithm, and the CIOU_Loss function in the YOLOv5 method is replaced by the EIOU_Loss function. The experimental results indicate that the improved algorithm is more accurate than the original YOLOv5s algorithm. In addition, the finer classification also significantly enhances the detection performance of the model.

Application of hepatitis B immunoglobulin in prevention of mother-to-child transmission of chronic hepatitis B in HBsAg- and HBeAg-positive mother.

The aim of our study was to compare the efficacy of two dosages of hepatitis B immunoglobulin (HBIG) combined with HBV vaccine (HBVac) to prevent mother-to-child transmission (MTCT) of hepatitis B in HBsAg- and HBeAg-positive mother. We enrolled 331 mother-infant pairs with HBsAg- and HBeAg-positive maternal state from the Women's Hospital School of Medicine of Zhejiang University. Newborns were randomly distributed into two groups according to the dosages of HBIG injection: 100 IU and 200 IU. Newborns from both groups were injected with HBVac in the same doses. We compared the immune outcomes between the two groups and explore the influencing factors of immune outcomes through regression analysis. There was no statistically significant relationship between HBsAg serological transmission of newborns and dosages of HBIG in HBsAg- and HBeAg-positive mother (p > .05). The Logistic regression showed that high DNA load is a risk factor for passive-active immunoprophylaxis failure for both 100 IU and 200 IU group, but higher-dosage HBIG is not necessary for higher-viral-load pregnant women with HBsAg- and HBeAg-positive. In conclusion, combined application of HBVac and a single dose of 100 IU HBIG can achieve the ideal MTCT interruption results for HBsAg- and HBeAg-positive pregnant women.IMPACT STATEMENTWhat is already known on this subject? Passive-active immunoprophylaxis is proved to be effective in preventing mother-to-child transmission of hepatitis B. Hepatitis B vaccine combined with 100 IU or 200 IU immunoglobulin is mostly recommended in China.What do the results of this study add? At present, there is still a lack scientific basis for improving existing strategies and measures to prevent mother-to-child transmission of hepatitis B in China.What are the implications of these findings for clinical practice and/or further research? 100 IU and 200 IU immunoglobulin show equivalent blocking effect, and combined use of hepatitis B vaccine and 100 IU immunoglobulin is more cost-effective.

Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians.

Centenarians (CENs) are excellent subjects to study the mechanisms of human longevity and healthy aging. Here, we analyzed the transcriptomes of 76 centenarians, 54 centenarian-children, and 41 spouses of centenarian-children by RNA sequencing and found that, among the significantly differentially expressed genes (SDEGs) exhibited by CENs, the autophagy-lysosomal pathway is significantly up-regulated. Overexpression of several genes from this pathway, CTSB, ATP6V0C, ATG4D, and WIPI1, could promote autophagy and delay senescence in cultured IMR-90 cells, while overexpression of the Drosophila homolog of WIPI1, Atg18a, extended the life span in transgenic flies. Interestingly, the enhanced autophagy-lysosomal activity could be partially passed on to their offspring, as manifested by their higher levels of both autophagy-encoding genes and serum beclin 1 (BECN1). In light of the normal age-related decline of autophagy-lysosomal functions, these findings provide a compelling explanation for achieving longevity in, at least, female CENs, given the gender bias in our collected samples, and suggest that the enhanced waste-cleaning activity via autophagy may serve as a conserved mechanism to prolong the life span from Drosophila to humans.

Off-label use of letrozole in Chinese short pubertal boys: Effectiveness, safety, and exposure-response analysis.

AIMS: Recently, letrozole has been used off-label to treat short pubertal boys. The experience on letrozole effectiveness and safety has been obtained primarily from Caucasian children. A simple extrapolation of the data to Chinese paediatric populations is questionable because of the substantial ethnic differences between the two populations. Therefore, the present study aimed to determine the effectiveness and safety of letrozole use in Chinese short pubertal boys as well as to establish an exposure-response relationship. METHODS: Forty-one Chinese boys were included in the study. Patients were given letrozole tablets (2.5 mg) once daily in combination with growth hormone, and follow-up visits were made after 1, 3, 6 and 12 months of treatment. Plasma samples were taken from clinical examinations and analysed using high performance liquid chromatography with fluorescence detection. RESULTS: After 1 year of treatment, 35 (88%) boys showed increased predicted adult heights. However, possible adverse drug reactions were seen in nine boys (22%). Predicted adult heights increased significantly from 168.4 ± 3.7 to 173.0 ± 4.2 cm, while oestrogen levels dropped from 33.2 ± 7.4 to 21.6 ± 7.3 pg/mL. Increments in predicted adult height were significantly correlated with trough letrozole concentrations (r = 0.39, P = .01). CONCLUSION: Letrozole treatment in Chinese pubertal populations should be further optimized, and more personalized therapies should be developed.

Predictive value of fibrinogen in identifying inflammatory bowel disease in active stage.

BACKGROUND: We aimed to externally validate for the first time the diagnostic ability of fibrinogen to identify active inflammatory bowel disease (IBD). METHODS: The research totally involved 788 patients with IBD, consisted of 245 ulcerative colitis (UC) and 543 Crohn' s disease (CD). The Mayo score and Crohn disease activity index (CDAI) assessed disease activity of UC and CD respectively. The independent association between fibrinogen and disease activity of patients with UC or CD was investigated by multivariate logistic regression analyses. Area under the receiver operating characteristic curve (AUROC) assessed the performance of various biomarkers in discriminating disease states. RESULTS: The fibrinogen levels in active patients with IBD significantly increased compared with those in remission stage (P < 0.001). Fibrinogen was an independent predictor to distinguish disease activity of UC (odds ratio: 2.247, 95% confidence interval: 1.428-3.537, P < 0.001) and CD (odds ratio: 2.124, 95% confidence interval: 1.433-3.148, P < 0.001). Fibrinogen was positively correlated with the Mayo score (r = 0.529, P < 0.001) and CDAI (r = 0.625, P < 0.001). Fibrinogen had a high discriminative capacity for both active UC (AUROC: 0.806, 95% confidence interval: 0.751-0.861) and CD (AUROC: 0.869, 95% confidence interval: 0.839-0.899). The optimum cut-off values of fibrinogen 3.22 was 70% sensitive and 77% specific for active UC, and 3.87 was 77% sensitive and 81% specific for active CD respectively. CONCLUSIONS: Fibrinogen is a convenient and practical biomarker to identify active IBD.

A Dynamic Interbody Cage Improves Bone Formation in Anterior Cervical Surgery: A Porcine Biomechanical Study.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) with a rigid interbody spacer is commonly used in the treatment of cervical degenerative disc disease. Although ACDF relieves clinical symptoms, it is associated with several complications such as pseudoarthrosis and adjacent segment degeneration. The concept of dynamic fusion has been proposed to enhance fusion and reduce implant subsidence rate and post-fusion stiffness; this pilot preclinical animal study was conducted to begin to compare rigid and dynamic fusion in ACDF. QUESTIONS/PURPOSES: Using a pig model, we asked, is there (1) decreased subsidence, (2) reduced axial stiffness in compression, and (3) improved likelihood of bone growth with a dynamic interbody cage compared with a rigid interbody cage in ACDF? METHODS: ACDF was performed at two levels, C3/4 and C5/6, in 10 pigs weighing 48 to 55 kg at the age of 14 to 18 months (the pigs were skeletally mature). One level was implanted with a conventional rigid interbody cage, and the other level was implanted with a dynamic interbody cage. The conventional rigid interbody cage was implanted in the upper level in the first five pigs and in the lower level in the next five pigs. Both types of interbody cages were implanted with artificial hydroxyapatite and tricalcium phosphate bone grafts. To assess subsidence, we took radiographs at 0, 7, and 14 weeks postoperatively. Subsidence less than 10% of the disc height was considered as no radiologic abnormality. The animals were euthanized at 14 weeks, and each operated-on motion segment was harvested. Five specimens from each group were biomechanically tested under axial compression loading to determine stiffness. The other five specimens from each group were used for microCT evaluation of bone ingrowth and ongrowth and histologic investigation of bone formation. Sample size was determined based on 80% power and an α of 0.05 to detect a between-group difference of successful bone formation of 15%. RESULTS: With the numbers available, there was no difference in subsidence between the two groups. Seven of 10 operated-on levels with rigid cages had subsidence on a follow-up radiograph at 14 weeks, and subsidence occurred in two of 10 operated-on levels with dynamic cages (Fisher exact test; p = 0.07). The stiffness of the unimplanted rigid interbody cages was higher than the unimplanted dynamic interbody cages. After harvesting, the median (range) stiffness of the motion segments fused with dynamic interbody cages (531 N/mm [372 to 802]) was less than that of motion segments fused with rigid interbody cages (1042 N/mm [905 to 1249]; p = 0.002). Via microCT, we observed bone trabecular formation in both groups. The median (range) proportions of specimens showing bone ongrowth (88% [85% to 92%]) and bone volume fraction (87% [72% to 100%]) were higher in the dynamic interbody cage group than bone ongrowth (79% [71% to 81%]; p < 0.001) and bone volume fraction (66% [51% to 78%]; p < 0.001) in the rigid interbody cage group. The percentage of the cage with bone ingrowth was higher in the dynamic interbody cage group (74% [64% to 90%]) than in the rigid interbody cage group (56% [32% to 63%]; p < 0.001), and the residual bone graft percentage was lower (6% [5% to 8%] versus 13% [10% to 20%]; p < 0.001). In the dynamic interbody cage group, more bone formation was qualitatively observed inside the cages than in the rigid interbody cage group, with a smaller area of fibrotic tissue under histologic investigation. CONCLUSION: The dynamic interbody cage provided satisfactory stabilization and percentage of bone ongrowth in this in vivo model of ACDF in pigs, with lower stiffness after bone ongrowth and no difference in subsidence. CLINICAL RELEVANCE: The dynamic interbody cage appears to be worthy of further investigation. An animal study with larger numbers, with longer observation time, with multilevel surgery, and perhaps in the lumbar spine should be considered.

A Traditional Chinese Medicine Traceability System Based on Lightweight Blockchain.

BACKGROUND: Recently, the problem of traditional Chinese medicine (TCM) safety has attracted attention worldwide. To prevent the spread of counterfeit drugs, it is necessary to establish a drug traceability system. A traditional drug traceability system can record the whole circulation process of drugs, from planting, production, processing, and warehousing to use by hospitals and patients. Once counterfeit drugs are found, they can be traced back to the source. However, traditional drug traceability systems have some drawbacks, such as failure to prevent tampering and facilitation of sensitive disclosure. Blockchain (including Bitcoin and Ethernet Square) is an effective technology to address the problems of traditional drug traceability systems. However, some risks impact the reliability of blockchain, such as information explosion, sensitive information leakage, and poor scalability. OBJECTIVE: To avoid the risks associated with the application of blockchain, we propose a lightweight block chain framework. METHODS: In this framework, both horizontal and vertical segmentations are performed when designing the blocks, and effective strategies are provided for both segmentations. For horizontal segmentation operations, the header and body of the blockchain are separated and stored in the blockchain, and the body is stored in the InterPlanetary File System. For vertical segmentation operations, the blockchain is cut off according to time or size. For the addition of new blocks, miners only need to copy the latest part of the blockchain and append the tail and vertical segmentation of the block through the consensus mechanism. RESULTS: Our framework could greatly reduce the size of the blockchain and improve the verification efficiency. CONCLUSIONS: Experimental results have shown that the efficiency improves compared with ethernet when a new block is added to the blockchain and a search is conducted.

Concomitant Tricuspid Annuloplasty in Patients Undergoing Totally Endoscopic Mitral Valve Surgery: A Propensity-Score Matched Analysis.

BACKGROUND: We aimed to evaluate the clinical outcomes of concomitant tricuspid annuloplasty (TAP) in patients undergoing totally endoscopic mitral valve surgery. METHODS: It is a single-center, retrospective study that enrolled a total of 173 patients who underwent mitral valve surgery combined with tricuspid annuloplasty between January 2019 and June 2020 in our institution. Patients who underwent totally endoscopic mitral valve surgery with concomitant tricuspid annuloplasty were categorized into the MIMVS-TAP group (N = 51), and patients who underwent mitral valve surgery with concomitant tricuspid annuloplasty through a median sternotomy were categorized into the MVS-TAP group (N = 122). The data collected included detailed demographic and perioperative data. Each patient in the MIMVS-TAP group was individually matched to a patient in the MVS-TAP group, using the propensity scores, and we obtained a matched sample of 51 patients in each group. Parametric and nonparametric tests were used to analyze outcomes. RESULTS: There were no differences in death rates or related major adverse events between the two groups after propensity score matched analysis. The total operation time was longer in the MIMVS + TAP group versus the MVS+TAP group, as were the mean duration of cardiopulmonary bypass time and the cross-clamp time. The mean duration of intensive care unit stay was longer in the MVS + TAP group compared with that of the MIMVS + TAP group, as was the duration of post-operative hospital stay. CONCLUSIONS: Totally endoscopic mitral valve surgery with concomitant tricuspid annuloplasty can improve a patient's prognosis, with comparable short-term outcomes to those of the open approaches.

Learning Curve from 100 Cases of Totally Thoracoscopic Mitral Valve Replacement.

BACKGROUND: To investigate and analyze the learning curve of totally thoracoscopic mitral valve replacement and provide a quantitative reference for cardiac surgeons to carry out the operation step by step. METHODS: The clinical data were retrospectively analyzed of 100 consecutive patients with totally thoracoscopic mitral valve replacement successively performed by the same surgeon in a single center from May 2019 to June 2020. The learning curve was divided into 2 stages by using cumulative sum analysis, and relevant surgical parameters and perioperative indicators were analyzed. RESULTS: The first stage of the learning curve is the skill acquisition stage, which includes 1 to 40 surgical procedures. The second stage is the proficiency stage, involving 41 to 100 operations. Among the surgical parameters of the patients in the 2 stages, detectable improvements were observed in operative time, cardiopulmonary bypass time, cross-clamp time, and intraoperative injury. After surgery, the amount of drainage, length of hospital stay, blood creatinine levels, and oxygenation index 24 h after surgery were also significantly different between the 2 groups (all P < .05). The age and sex distributions of the patients were balanced, and there was no statistically significant difference in terms of conversion to median sternotomy between the 2 stages (P > .05). CONCLUSIONS: Cumulative sum analysis was used to accurately analyze the learning curve of totally thoracoscopic mitral valve replacement, indicating that 40 cases are needed to master the technique.

[Establishment of a field visual detection method for genetically modified maize 'Shuangkang'12-5 by fluorescence RPA].

The genetically modified (GM) maize 'Shuangkang'12-5 has good insect resistance and herbicide tolerance, which is one of the first series of GM maizes obtained a safety certificate in China, and it has broad application prospect in the future. This study established an on-site rapid detection method for GM 'Shuangkang'12-5 based on recombinase polymerase amplification (RPA) technology, which primes and probe were designed according to the specific flank sequence. Then the best combination of primers and probe was obtained through a screeing process. The amplification results of fluorescence RPA can be directly visualized under blue light. The results showed that the visual detection system of GM 'Shuangkang'12-5 with high specificity, and the detection sensitivity of the method could reached 10 copies. Further research found that the RPA amplification system had a wide range of temperature (34℃-46℃). According to this property, the common self-heating warm pastes on the market were used replace the traditional heating instruments to stimulate the RPA.The results showed that the self-heating warm paste meets the temperature requirement of the RPA system. Finally, we combined the self-heating warm pastes with the RPA visual detection system to conduct on-site detection of GM 'Shuangkang'12-5, and compared the results with the detection results of qPCR. The detection showed that the results of on-site visual detection method established in this study were consistent with the detection results of the qPCR. Moreover, the visual detection method was more shorter in time and the final detection result was clear and easy to distinguish. The rapid on-site visual detection method for GM 'Shuangkang' 12-5 established in this study has high specificity, high sensitivity and convenience. It not only meets the needs of on-site rapid detection of GM 'Shuangkang'12-5, but also provides highlight for the development of other on-site rapid detection methods.

Nanoplastics Promote Microcystin Synthesis and Release from Cyanobacterial Microcystis aeruginosa.

Although the fate of nanoplastics (<100 nm) in freshwater systems is increasingly well studied, much less is known about its potential threats to cyanobacterial blooms, the ultimate phenomenon of eutrophication occurrence worldwide. Previous studies have evaluated the consequences of nanoplastics increasing the membrane permeability of microbes, however, there is no direct evidence for interactions between nanoplastics and microcystin; intracellular hepatotoxins are produced by some genera of cyanobacteria. Here, we show that the amino-modified polystyrene nanoplastics (PS-NH2) promote microcystin synthesis and release from Microcystis aeruginosa, a dominant species causing cyanobacterial blooms, even without the change of coloration. We demonstrate that PS-NH2 inhibits photosystem II efficiency, reduces organic substance synthesis, and induces oxidative stress, enhancing the synthesis of microcystin. Furthermore, PS-NH2 promotes the extracellular release of microcystin from M. aeruginosa via transporter protein upregulation and impaired cell membrane integrity. Our findings propose that the presence of nanoplastics in freshwater ecosystems might enhance the threat of eutrophication to aquatic ecology and human health.