Access to cyclohexadiene and benzofuran derivatives via catalytic arene cyclopropanation of α-cyanodiazocarbonyl compounds.

The arene cyclopropanation between diazo compounds and benzene is well known to produce a tautomeric mixture of norcaradiene and cycloheptatriene in favour of the latter species. Nevertheless, previous studies have suggested that the initially formed norcaradiene can be stabilized by a C-7 cyano group with prevention of its 6π-electrocyclic ring opening. According to this feature, a synthetic route to functionalized cyclohexadienes has been designed using α-cyanodiazoacetates and α-diazo-ß-ketonitriles as the starting materials, respectively. The Rh2(esp)2-catalyzed arene cyclopropanation of α-cyanodiazoacetates in benzene afforded the expected 7-alkoxycarbonyl-7-cyanonorcaradienes as isolable compounds, which then served as templates for the second cyclopropanation with ethyl diazoacetate or α-cyanodiazocarbonyls to enable the formation of bis(cyclopropanated) adducts. Their subsequent treatment with SmI2 triggered a double ring-opening process, allowing for the generation of 1,4- and/or 1,3-cyclohexadienes as either regio- or diastereomeric mixtures. On the other hand, the norcaradienes generated from phenyl- or methyl-substituted α-diazo-ß-ketonitriles were found to undergo an in situ rearrangement to yield dihydrobenzofurans that could be converted to benzofuran derivatives by DDQ oxidation.

Relationship between the magnitude of haemoglobin changes and long-term mortality in patients with sepsis: a retrospective cohort study.

BACKGROUND: Sepsis is a common and severe disease with a high mortality rate in intensive care unit (ICU). The hemoglobin (HGB) level is a key parameter for oxygen supply in sepsis. Although HGB is associated with the progression of inflammation in sepsis patients, its role as a marker following sepsis treatment remains unclear. Here, we studied the correlation between early temporal changes in HGB levels and long-term mortality rates in septic patients. METHOD: In this retrospective study of data on patients with sepsis from the Medical Information Mart for Intensive Care (MIMIC) IV database, the outcome was long-term mortality. Patients were divided based on the cut-off of the HGB percentage for receiver operating characteristic (ROC) curve calculation. Kaplan-Meier (KM) survival curves and Cox proportional hazards regression models were used to analyse the associations between groups and outcomes. Propensity score matching (PSM) was used to verify the results. RESULTS: In this study, 2042 patients with sepsis and changes in HGB levels at day 4 after admission compared to day 1 were enrolled and divided into two groups: group 1 (n = 1147) for those with reduction of HGB < 7% and group 2 (n = 895) for those with dropping ≥ 7%. The long-term survival chances of sepsis with less than a 7% reduction in the proportion of HGB at day four were significantly higher than those of patients in the group with a reduction of 7% or more. After adjusting for covariates in the Cox model, the hazard ratios (HRs) with 95% confidence intervals (CIs) for long-term all-cause mortality in the group with a reduction of 7% or more were as follows: 180 days [HR = 1.41, 95% CI (1.22 to 1.63), P < 0.001]; 360 days [HR = 1.37, 95% CI (1.21 to 1.56), P < 0.001]; 540 days [HR = 1.35, 95% CI (1.20 to 1.53), P < 0.001]; 720 days [HR = 1.45, 95% CI (1.29 to 1.64), P < 0.001]. Additionally, the long-term survival rates, using Kaplan-Meier analysis, for the group with a reduction of 7% or more were lower compared to the group with less than 7% reduction at 180 days (54.3% vs. 65.3%, P < 0.001), 360 days (42.3% vs. 50.9%, P < 0.001), 540 days (40.2% vs. 48.6%, P < 0.001), and 720 days (35.5% vs. 46.1%, P < 0.001). The same trend was obtained after using PSM. CONCLUSION: A ≥ 7% decrease in HGB levels on Day 4 after admission was associated with worse long-term prognosis in sepsis patients admitted to the ICU.

Influence of systolic blood pressure trajectory on in-hospital mortality in patients with sepsis.

BACKGROUND: Numerous studies have investigated the mean arterial pressure in patients with sepsis, and many meaningful results have been obtained. However, few studies have measured the systolic blood pressure (SBP) multiple times and established trajectory models for patients with sepsis with different SBP trajectories. METHODS: Data from patients with sepsis were extracted from the Medical Information Mart for Intensive Care-III database for inclusion in a retrospective cohort study. Ten SBP values within 10 h after hospitalization were extracted, and the interval between each SBP value was 1 h. The SBP measured ten times after admission was analyzed using latent growth mixture modeling to construct a trajectory model. The outcome was in-hospital mortality. The survival probability of different trajectory groups was investigated using Kaplan-Meier (K-M) analysis, and the relationship between different SBP trajectories and in-hospital mortality risk was investigated using Cox proportional-hazards regression model. RESULTS: This study included 3034 patients with sepsis. The median survival time was 67 years (interquartile range: 56-77 years). Seven different SBP trajectories were identified based on model-fit criteria. The in-hospital mortality rates of the patients in trajectory classes 1-7 were 25.5%, 40.5%, 11.8%, 18.3%, 23.5%, 13.8%, and 10.5%, respectively. The K-M analysis indicated that patients in class 2 had the lowest probability of survival. Univariate and multivariate Cox regression analysis indicated that, with class 1 as a reference, patients in class 2 had the highest in-hospital mortality risk (P < 0.001). Subgroup analysis indicated that a nominal interaction occurred between age group and blood pressure trajectory in the in-hospital mortality (P < 0.05). CONCLUSION: Maintaining a systolic blood pressure of approximately 140 mmHg in patients with sepsis within 10 h of admission was associated with a lower risk of in-hospital mortality. Analyzing data from multiple measurements and identifying different categories of patient populations with sepsis will help identify the risks among these categories.

Soluble Klotho-integrin ß1/ERK1/2 pathway ameliorates myocardial fibrosis in diabetic cardiomyopathy.

Soluble Klotho (sKL) is closely related to insulin resistance, which is a major factor in the progression of diabetic cardiomyopathy (DCM). The purpose of this study was to investigate the role of sKL in the regulation of DCM and the mechanism involved. A mouse model of type 2 diabetes was induced by high-fat diet and streptozotocin injection. An insulin-resistant cardiac fibroblast model was established by high glucose and high insulin. KL gene overexpression was achieved in vivo and vitro through transfection with an adenovirus-harboring KL-cDNA. Gene overexpression was used to evaluate the role of sKL in the pathophysiologic characteristics of DCM. Insulin-resistant cardiac fibroblasts reduced sKL expression and collagen deposition. Diabetic mice constructed by streptozotocin exhibited severe insulin resistance, inflammation, fibrosis, left ventricular dysfunction, and sKL downregulation. The overexpression of sKL mitigated insulin resistance and metabolic disturbance; inflammation, fibrosis, and upregulated collagen I/III content ratio in diabetic state were significantly reduced. Our findings were accompanied by notable moderation of cardiac function. Further, blunted phosphorylation of Akt was restored with sKL gene overexpression, and activated phosphorylation of extracellular signal-regulated kinase 1/2 in DCM was reduced. Our results suggest that sKL protein overexpression exerts a defensive measure by ameliorating selective insulin resistance in mouse DCM, thus revealing its underlying mechanism for potential human DCM treatment.

Association of lactate to albumin ratio and bicarbonate with short-term mortality risk in patients with acute myocardial infarction.

BACKGROUND: Previous studies have indicated that the ratio of lactate/albumin (L/A) has predictive value for the prognosis of critically ill patients with heart failure. Some studies have also indicated that a low serum bicarbonate concentration is inversely related to the mortality risk of patients with cardiogenic shock. However, the value of bicarbonate and the L/A ratio for predicting the mortality risk of patients with acute myocardial infarction (AMI) is still unclear. We therefore conducted a retrospective study to research this problem. METHODS: The subjects of this study were patients with AMI, and the data source was the Medical Information Mart for Intensive Care III database. The primary endpoint was 30-day all-cause mortality after admission. The Receiver operating characteristic (ROC) curve was used to compare the predictive value of L/A ratio, lactate and albumin for end-point events. The effects of different L/A ratio levels and different bicarbonate concentrations on 7-day and 30-day all-cause mortality were compared using Kaplan-Meier (K-M) curves. Hazard ratios for different L/A ratio and different bicarbonate concentrations were investigated using COX proportional hazards models. RESULTS: The Area Under Curve (AUC) of L/A ratio, lactate, and albumin were 0.736, 0.718, and 0.620, respectively. (1) L/A ratio: The patients were divided into three groups according to their L/A ratio: tertile T1 (L/A ratio ≤ 0.47), tertile T2 (L/A ratio ≤ 0.97), and tertile T3 (L/A ratio > 0.97). The T2 and T3 groups had higher 30-day all-cause mortality risks than the T1 group. The restricted cubic spline (RCS) model indicated that there was a nonlinear relationship between L/A ratio and 30-day mortality (P < 0.05). (2) Bicarbonate concentration: The patients were also divided into three groups based on their bicarbonate concentration: G1 (22-27 mmol/L), G2 (< 22 mmol/L), and G3 (> 27 mmol/L). The G2 and G3 groups had higher 30-day all-cause mortality risks than the G1 group. The RCS model indicated that there was a nonlinear relationship between bicarbonate concentration and 30-day mortality (P < 0.05). The RCS model indicated that there was a nonlinear relationship between hemoglobin level and 30-day all-cause mortality (P < 0.05). CONCLUSION: L/A ratio and bicarbonate concentration and hemoglobin level have predictive value for predicting 30-day mortality in patients with acute myocardial infarction.

Rhodium-Catalyzed Aerobic Decomposition of 1,3-Diaryl-2-diazo-1,3-diketones: Mechanistic Investigation and Application to the Synthesis of Benzils.

The conversion of 1,3-diaryl-2-diazo-1,3-diketones to 1,2-daryl-1,2-diketones (benzils) is reported based on a rhodium(II)-catalyzed aerobic decomposition process. The reaction occurs at ambient temperatures and can be catalyzed by a few dirhodium carboxylates (5 mol %) under a balloon pressure of oxygen. Moreover, an oxygen atom from the O2 reagent is shown to be incorporated into the product, and this is accompanied by the extrusion of a carbonyl unit from the starting materials. Mechanistically, it is proposed that the decomposition may proceed via the interaction of a ketene intermediate resulting from a Wolff rearrangement of the carbenoid, with a rhodium peroxide or peroxy radical species generated upon the activation of molecular oxygen. The proposed mechanism has been supported by the results from a set of controlled experiments. By using this newly developed strategy, a large array of benzil derivatives as well as 9,10-phenanthrenequinone were synthesized from the corresponding diazo substrates in varying yields. On the other hand, the method did not allow the generation of benzocyclobutene-1,2-dione from 2-diazo-1,3-indandione because of the difficulty of inducing the initial rearrangement.

Rhodium-catalyzed cyclization of acceptor-substituted biphenyl α-diazoketones: a study of the substitution effect on chemoselectivity.

A range of biphenyl α-diazoketones containing various electron-withdrawing groups (EWG = COCH3, CN, CO2Et, COPh, SO2CH3, SO2Ph) on diazo carbon has been investigated for rhodium(ii)-catalyzed intramolecular cyclization. Among which, the α-acetyl, carboxylate and cyano substituted substrates show markedly different selectivity between aromatic substitution and aromatic cycloaddition processes, affording phenanthrol and/or benz[α]azulenone products in varying ratios. The selectivity is mainly directed by α-substitutions, and is also possibly influenced by the substituents on the biphenyl ring. Moreover, high chemoselectivity for aromatic substitution over cycloaddition is observed for the α-benzoyl and sulfonyl substituted substrates. But in addition to phenanthrols, these reactions produce aromatic ketones and/or 1,2-diketones as unprecedented products obtained from diazo precursors. Mechanistic rationales are given in the report.

Access to functionalized bicyclo[4,3,0]nonenes via palladium-catalyzed oxidative cyclization of 2-allylcyclohexyl oximes.

A new palladium-catalyzed oxidative cyclization process leading to the functionalized bicyclo[4,3,0]nonenes is serendipitously discovered during attempts to form aza-heterocycle by the amino-Heck reaction of trans-2-vinylclohexyl phosphinyloxime. Under the influence of Pd(dba)2/Et3N/1:1 N2-O2 (1:1, v/v) (Method A) or Pd(OAc)2/Et3N/O2 (Method B), the reactions afford the substituted cis-1-hydroxyl-8-formyl-bicyclo[4,3,0]non-8(9)-enes or bicycle[4,3,0]non-1(9)-en-8-ones in varying yields with the incorporation of molecular oxygen into the structures. The 5,6-bicyclic scaffold of these products is presumably derived from tandem double intramolecular cyclization followed by the ring-opening of an aza-palladium(II) tricyclic intermediate.

Development and validation of a nomogram for predicting hospitalization longer than 14 days in pediatric patients with ventricular septal defect-a study based on the PIC database.

Background: Ventricular septal defect is a common congenital heart disease. As the disease progresses, the likelihood of lung infection and heart failure increases, leading to prolonged hospital stays and an increased likelihood of complications such as nosocomial infections. We aimed to develop a nomogram for predicting hospital stays over 14 days in pediatric patients with ventricular septal defect and to evaluate the predictive power of the nomogram. We hope that nomogram can provide clinicians with more information to identify high-risk groups as soon as possible and give early treatment to reduce hospital stay and complications. Methods: The population of this study was pediatric patients with ventricular septal defect, and data were obtained from the Pediatric Intensive Care Database. The resulting event was a hospital stay longer than 14 days. Variables with a variance inflation factor (VIF) greater than 5 were excluded. Variables were selected using the least absolute shrinkage and selection operator (Lasso), and the selected variables were incorporated into logistic regression to construct a nomogram. The performance of the nomogram was assessed by using the area under the receiver operating characteristic curve (AUC), Decision Curve Analysis (DCA) and calibration curve. Finally, the importance of variables in the model is calculated based on the XGboost method. Results: A total of 705 patients with ventricular septal defect were included in the study. After screening with VIF and Lasso, the variables finally included in the statistical analysis include: Brain Natriuretic Peptide, bicarbonate, fibrinogen, urea, alanine aminotransferase, blood oxygen saturation, systolic blood pressure, respiratory rate, heart rate. The AUC values of nomogram in the training cohort and validation cohort were 0.812 and 0.736, respectively. The results of the calibration curve and DCA also indicated that the nomogram had good performance and good clinical application value. Conclusion: The nomogram established by BNP, bicarbonate, fibrinogen, urea, alanine aminotransferase, blood oxygen saturation, systolic blood pressure, respiratory rate, heart rate has good predictive performance and clinical applicability. The nomogram can effectively identify specific populations at risk for adverse outcomes.

Technical Notes and Clinical Outcomes of Full-Endoscopic Interbody Fusion Via Transforaminal Approach for Hard Disc Herniations in Thoracolumbar Junction.

OBJECTIVE: Obtaining sufficient decompression and solid fusion and avoiding approach-related injuries simultaneously are still challenging for the treatment of hard disc herniation in thoracolumbar junction. A combined full-endoscopic decompression and interbody fusion via a transforaminal approach was used to achieve this goal. The purpose of this study was to introduce the technical notes and clinical outcomes of this novel technique. METHODS: Twenty segments of hard disc herniations in the thoracolumbar junction of 14 patients treated with full-endoscopic interbody fusion via the transforaminal approach between January 2018 and September 2021 were analyzed. The patients were an average age of 43.3 years. Full-endoscopic interbody fusion and discectomy via the transforaminal approach were performed under local anesthesia, followed by percutaneous pedicle screw system fixation under general anesthesia. Imaging, including magnetic resonance imaging (MRI), computed tomography (CT), and X-ray, was carried out. MRI was performed on the second day and 3 months postoperatively. CT was performed on the second day, 6 months, and 1 year (as needed) postoperatively. Back and radicular pain, neurological function, and thoracic spine function were scored using a visual analog scale, the Nurick scale, and modified Japanese Orthopaedic Association (mJOA) scale, and the Oswestry disability index at 1 week, 3 months, 6 months, and 1 year postoperatively. RESULTS: All the operations were successfully completed, and no intraoperative conversion of the surgical methods occurred. Postoperative thoracolumbar junction MRI and CT examinations of all the patients revealed a sufficiently decompressed spinal cord or cauda equina, without any residual compression. At the 1-year follow-up, all the surgical segments were fused. Back and radicular pain was relieved in all the patients, and neurological function was restored. The average recovery rate of the mJOA was 72.5%, including seven excellent, five good, and two fair cases. Although dural tears occurred in two cases during the operation, no cerebrospinal fluid leakage or pseudomeningocele occurred during follow-up. No other surgical complications were noted. CONCLUSIONS: A combined full-endoscopic decompression and interbody fusion via a transforaminal approach can achieve complete spinal canal decompression and solid interbody fusion with fewer approach-related injuries. It is a safe and effective minimally invasive spine surgery for treating hard disc herniation in the thoracolumbar junction.

Association between glucocorticoid use and all-cause mortality in critically ill patients with heart failure: A cohort study based on the MIMIC-III database.

Background: Heart failure (HF) is the terminal stage of various heart diseases. Conventional treatments have poor efficacy, and diuretic resistance can present. Previous studies have found that the use of glucocorticoids can enhance the diuretic effect of patients with heart failure and reduce heart failure symptoms. However, the relationship between glucocorticoid use and mortality in patients with heart failure in intensive care units is unclear. Objectives: The aim of this study was to determine the association between glucocorticoid use and all-cause mortality in critically ill patients with heart failure. Methods: The information on patients with heart failure in this study was extracted from the MIMIC-III (Medical Information Mart for Intensive Care-III) database. Patients in the glucocorticoid and non-glucocorticoid groups were matched using propensity scores. The Kaplan-Meier method was used to explore the difference in survival probability between the two groups. A Cox proportional-hazards regression model was used to analyze the hazard ratios (HRs) for the two patient groups. Subgroup analyses were performed with prespecified stratification variables to demonstrate the robustness of the results. Results: The study included 9,482 patients: 2,099 in the glucocorticoid group and 7,383 in the non-glucocorticoid group. There were 2,055 patients in each group after propensity-score matching. The results indicated that the non-glucocorticoid group was not significantly associated with reduced mortality in patients with heart failure during the 14-day follow-up period [HRs = .901, 95% confidence interval (CI) = .767-1.059]. During the follow-up periods of 15-30 and 15-90 days, the mortality risk was significantly lower in the non-glucocorticoid group than in the glucocorticoid group (HRs = .497 and 95% CI = .370-.668, and HRs = .400 and 95% CI = .310-.517, respectively). Subgroup analyses indicated no interaction among each stratification variable and glucocorticoid use. Conclusion: Glucocorticoid use was associated with an increased mortality risk in critically ill patients with heart failure.

Development and validation of an interpretable machine learning model-Predicting mild cognitive impairment in a high-risk stroke population.

Background: Mild cognitive impairment (MCI) is considered a preclinical stage of Alzheimer's disease (AD). People with MCI have a higher risk of developing dementia than healthy people. As one of the risk factors for MCI, stroke has been actively treated and intervened. Therefore, selecting the high-risk population of stroke as the research object and discovering the risk factors of MCI as early as possible can prevent the occurrence of MCI more effectively. Methods: The Boruta algorithm was used to screen variables, and eight machine learning models were established and evaluated. The best performing models were used to assess variable importance and build an online risk calculator. Shapley additive explanation is used to explain the model. Results: A total of 199 patients were included in the study, 99 of whom were male. Transient ischemic attack (TIA), homocysteine, education, hematocrit (HCT), diabetes, hemoglobin, red blood cells (RBC), hypertension, prothrombin time (PT) were selected by Boruta algorithm. Logistic regression (AUC = 0.8595) was the best model for predicting MCI in high-risk groups of stroke, followed by elastic network (ENET) (AUC = 0.8312), multilayer perceptron (MLP) (AUC = 0.7908), extreme gradient boosting (XGBoost) (AUC = 0.7691), and support vector machine (SVM) (AUC = 0.7527), random forest (RF) (AUC = 0.7451), K-nearest neighbors (KNN) (AUC = 0.7380), decision tree (DT) (AUC = 0.6972). The importance of variables suggests that TIA, diabetes, education, and hypertension are the top four variables of importance. Conclusion: Transient ischemic attack (TIA), diabetes, education, and hypertension are the most important risk factors for MCI in high-risk groups of stroke, and early intervention should be performed to reduce the occurrence of MCI.

Modified Unilateral Biportal Endoscopic Lumbar Discectomy Results in Improved Clinical Outcomes.

OBJECTIVE: To evaluate and describe the clinical efficacy and safety of a modified unilateral biportal endoscopic lumbar discectomy. METHODS: From February 2019 to February 2020, patients who met the inclusion criteria were treated using a modified unilateral biportal endoscopic lumbar discectomy. During the operation, the herniated disc was removed and the ligamentum flavum was preserved. Clinical efficacy was assessed via postoperative imaging and follow-up. RESULTS: A total of 70 patients were followed up for more than 2 years, including 51 males and 19 females, aged 49.4 ± 16.0 years. All operations were completed and no complications were noted. Postoperative lumbar magnetic resonance imaging showed that the decompression of the nerve root was sufficient and the ligamentum flavum was preserved in all patients. Postoperative lumbar CT showed that the caudal lamina and inferior articular process of the cephalad vertebral were partially removed. Lower back and leg pain were significantly relieved after surgery, and the Oswestry Disability Index was significantly improved compared to presurgery measurements (P ＜ 0.01). After 2 years of follow-up, the sensory and muscle strength of nerve roots were significantly recovered (P ＜ 0.01). According to the MacNab score of the patients, 40 cases were defined as "excellent," 26 cases were "good," 2 cases were "fair," and 2 cases were "poor." CONCLUSIONS: Modified unilateral biportal endoscopic lumbar discectomy can completely remove a lumbar herniated disc; relieve lower back and leg pain; improve lumbar function; reduce the risk of dural tearing, cerebrospinal fluid leakage, and epidural hematoma; and reduce the epidural adhesion and arachnoiditis caused by ligamentum flavum resection.

Development and validation of a simple nomogram for predicting the short-term prognosis of patients with pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is a disease caused by blood clots, tumor embolism, and other emboli within the pulmonary arteries. Various scoring scales are used for PE. One such same is the PESI, but it has 12 variables, making it inconvenient for clinical application. OBJECTIVES: The aim of this study was to develop a new simple nomogram model to assess 30-day survival in PE patients. The new nomogram makes it easier and faster for clinicians to assess the prognosis of patients with PE. METHODS: We collected data about the patients with PE from the Medical Information Mart for Intensive Care-III (MIMIC-III) database and used the receiver operating characteristic (ROC) curve, area under the ROC curve (AUROC), calibration plot, integrated discrimination improvement (IDI), and decision curve analysis (DCA) to evaluate the predictive power of the new model, and compared these with the PESI. RESULTS: According to the multivariable Cox regression model results, alongside the actual clinical conditions, we included the following seven variables: race, bicarbonate, age, tumor, systolic blood pressure (SBP), body temperature, and oxygen saturation (Spo2). The AUROC of the new model was greater than 0.70. Its IDI exceeded 0, but with P-value>0.05. CONCLUSION: The predictive performance of the new model was not worse than the PESI, but the new model only has seven variables, and is therefore more convenient for clinicians to use.

[Clinical safety about repairing the peripheral nerve defects with chemically extracted acellular nerve allograft].

OBJECTIVE: To discuss the clinical safety about repairing the peripheral nerve defects with the acellular allogeneic nerve. METHODS: The 41 patients (male 38, female 3, age 10 - 55 years old, average 28.9 years old) who were performed chemically extracted acellular nerve allograft transplanting to repair nerve defects from 2002 to 2011. The average interval from injury to nerve repairing was 4.1 months (range, 10 hours to 9 months). There were 41 cases nerve defects including 10 brachial plexus nerves, 3 radial nerves of upper arm, 4 ulnar nerves of forearm, 12 digital and toe nerves, 2 sciatic nerves, 2 femoral nerves, 3 tibial nerves and 5 common peroneal nerves. There were 12 cases combined fractures and 20 soft tissue injury or defects. The average length of the nerve allograft to bridge the nerve defects was 6.1 cm (range, 2 - 10 cm). No immunosuppressive drugs were used in all cases. The clinical safety was evaluated through physical examination, blood biochemistry and immunity detection. RESULTS: All cases were followed up post-operation. They got primary wound healing except 2 superficial infection who got delay healing through dressings changing. No any adverse effects happened including immunological rejection, hypersensitivity reaction, deep infection, hepatotoxicity and nephrotoxicity. CONCLUSIONS: It is safe and feasible to repairing human peripheral nerve defects with chemically extracted acellular nerve allograft.

Long noncoding RNA CDKN2B-AS1 silencing protects against esophageal cancer cell invasion and migration by inactivating the TFAP2A/FSCN1 axis.

Esophageal cancer (EC) is the most aggressive malignancy in the gastrointestinal tract. Long noncoding RNA cyclin-dependent kinase inhibitor 2 B antisense RNA 1 (CDKN2B-AS1) is implicated in EC development. However, the specific mechanisms involved remain poorly defined. Therefore, this research aimed to explore the mechanism of action of CDKN2B-AS1 in EC. Quantitative real-time polymerase chain reaction was conducted to measure CDKN2B-AS1 expression in EC cells and western blotting was utilized to evaluate transcription factor AP-2 alpha (TFAP2A) and fascin actin-bundling protein 1 (FSCN1) expression. After gain-of-function and loss-of-function assays, cell proliferation, migration, invasion, apoptosis, and apoptosis-related protein expression were assessed using cell counting kit-8, scratch tests, Transwell assays, flow cytometry, and western blotting, respectively. The binding relationship between CDKN2B-AS1 and TFAP2A was assessed by RNA immunoprecipitation and RNA pull-down assays. The binding relationship between TFAP2A and FSCN1 was evaluated using dual-luciferase reporter and chromatin immunoprecipitation assays. Tumor xenografts from nude mice were used for in vivo verification. CDKN2B-AS1, TFAP2A, and FSCN1 were upregulated in EC cells. Mechanistically, CDKN2B-AS1 transcriptionally activated FSCN1 by recruiting TFAP2A to the FSCN1 promoter. Silencing CDKN2B-AS1 or TFAP2A suppressed EC cell proliferative, migrating, and invasive properties and augmented apoptosis. TFAP2A was bound to CDKN2B-AS1 and the FSCN1 promoter. Overexpression of TFAP2A or FSCN1 abolished the effects of CDKN2B-AS1-silencing on EC cell function. CDKN2B-AS1 silencing curtailed tumorigenesis in nude mice, which was nullified by the upregulation of TFAP2A or FSCN1. Our findings demonstrated the antioncogenic effects of silencing CDKN2B-AS1 in EC through inactivation of the TFAP2A/FSCN1 axis.

[Clinical efficacy of different rehabilitation modes for lumbar degenerative diseases after operation].

OBJECTIVE: To compare clinical effects of different postoperative rehabilitation modes on lumbar degenerative diseases, and explore influence of rehabilitation mode and other factors on postoperative effect. METHODS: From June 2013 to July 2016, totally 900 patients were admitted from nine tertiary hospitals in Beijing to perform single segment bone grafting and internal fixation due to lumbar degenerative diseases were prospectively analyzed. There were 428 males and 472 females, the age of patient over 18 years old, with an average of (51.42±12.41) years old;according to patients' subjective wishes and actual residence conditions, all patients were divided into three groups, named as observation group 1 (performed integrated rehabilitation approach and orthopedic treatment model intervention), observation group 2 (performed integrated rehabilitation approach and orthopedic treatment, classified rehabilitation model intervention), and control group(performed routine rehabilitation model intervention). Visual analogue scale(VAS), Oswestry Disability Index(ODI) and Japanese Orthopaedic Association (JOA) were used to evaluate postoperative efficacy among three groups at 24 weeks. Possible factors affecting the postoperative efficacy including age, age grouping, gender, body mass index (BMI), BMI grouping, education level, visiting hospital, payment method of medical expenses, preoperative complications, preoperative JOA score, clinical diagnosis, surgery section, operative method, intraoperative bleeding volume, postoperative complications and rehabilitation mode were listed as independent variables, and postoperative ODI score at 24 weeks as dependent variables. Univariate analysis was used to analyze relationship between influencing factors and postoperative efficacy. Multiple linear regression was used to analyze relationship between influencing factors, rehabilitation mode and postoperative ODI score at 24 weeks, in further to find out the main reasons which affect postoperative efficacy, and to analyze impact of rehabilitation mode on postoperative efficacy. RESULTS: All patients were followed up for 24 weeks after operation. All incisions healed at stage I with stable internal fixation. (1)Evaluation of postoperative efficacy:① There were no statistical differences in preoperative VAS and ODI among three groups(P>0.05), the degree of pain and dysfunction decreased among three groups after operation, and had differences in postoperative VAS and ODI among three groups (P<0.05). There were no significant differences between observation group 1 and observation group 2(P>0.05); while compared with observation group 1 and control group, observation group 2 and control group, there were significant differences (P<0.05). ②The function among three groups were improved in varying degrees after operation. There was difference in JOA score among three groups before operation and 24 weeks after operation (P<0.05). There were no difference in JOA score among three groups between observation group 1 and observation group 2 (P>0.05);while compared with observation group 1 and control group, observation group 2 and control group, there were significant differences (P<0.05). (2)Influencing factors at 24 weeks after operation:①Univariate analysis showed gender, age, age grouping, education level, preoperative complications, clinical diagnosis, operative section, operative method, preoperative JOA score and rehabilitation mode had statistical significance with postoperative ODI score at 24 weeks (P<0.05). BMI, BMI grouping, payment method of medical expenses, visiting hospital, intraoperative bleeding volume, postoperative complications had no statistical significance with postoperative ODI score at 24 weeks (P<0.05).②Multivariate analysis results showed gender, rehabilitation mode, age, preoperative JOA score entered the equation eventually, stepwise multiple linear equation obtained had statistical significance (F=12.294, P= 0.000). Among rehabilitation mode, standardized regression coefficient of the integrated rehabilitation approach and orthopedic treatment with classified rehabilitation model was absolute value of the largest (0.176), which had the greatest influence on postoperative curative effect. The degree of dysfunction in control group was higher than that in observation group 1 and observation group 2. Postoperative dysfunction was more severe in males than that of in females. Older age has higher degree of dysfunction after operation. Lower preoperative JOA score has higher degree of dysfunction after operation. CONCLUSION: Preoperative JOA score, gender, age could predict postoperative clinical effects of lumbar degenerative diseases in varying degrees treated with single level bone graft fusion and internal fixation. Different rehabilitation modes could improve clinical effects. Intergrated rehabilitation orthopedic treatment model and integrated rehabilitation approach and orthopedic treatment with classifiedrehabilitation model are superior to conventional rehabilitation model in improving patients' postoperative function and relieving pain, which is worthy of promoting in clinical.

Investigation on Lewis acid mediated Diels-Alder reactions of 2-phosphono-2-alkenoates. Application to total synthesis of (+/-)-alpha-alasken-8-one via reductive alkylation of resulting adduct.

The Lewis acid mediated Diels-Alder reactions of three 2-phosphono-2-alkenoates including triethyl 2-phosphonoacrylate (1), triethyl 2-phosphonobut-2-enoate (2), and ethyl 2-(diethoxyphosphono)-3-methylbut-2-enoate (3) have been investigated. Of several Lewis acids tested, tin(IV) chloride was shown to be the most effective at enhancing the regio- and stereoselectivity of the reactions of 1 with the electron-rich dienes to result in the formation of the single regio- and/or stereoisomers in good yields. Bearing the beta methyl group(s), 2 displayed much less reactivity than 1 while 3 was completely unreactive under the study's conditions. Throughout the investigation, we found that the cycloadditions of 2, especially of the Z-isomer, could be efficiently induced by using zinc chloride at elevated temperatures. Furthermore, a lithium naphthalenide (LN)-induced reductive alkylation process was applied to the resulting Diels-Alder adducts 4 to allow the phosphono group at the quaternary carbon centers to be replaced by various alkyl groups to afford the alkyl-substituted esters 12, therefore practically turning 1 and 2 into the useful synthetic equivalents of the corresponding 2-alkyl 2-alkenoates that usually display poor Diels-Alder reactivity. Application of this combined operation has facilitated the total synthesis of the sesquiterpene natural product alpha-alasken-8-one (8) in racemic form.

A convenient new procedure for converting primary amides into nitriles.

An operationally simple and high-yielding procedure has been developed for the conversion of primary amides to the corresponding nitriles, using ethyl dichlorophosphate/DBU as the mild dehydrating agent.

Clinical Anatomy and Measurement of the Medial Branch of the Spinal Dorsal Ramus.

Percutaneous block and neurotomy of the medial branch of the spinal dorsal ramus has shown excellent results in treating facet joint-mediated low back pain. This study aimed to describe the clinical anatomy of the medial branch and its measurements.We dissected the lumbar spine of 12 adult cadavers (24 sides) and measured the distances between the medial branch and various anatomical landmarks. The distances were compared between L1 and L5 vertebrae.The distance between the dorsal ramus bifurcation and the superior border of the root of the transverse process was 3.52 ±â€Š1.15 mm, 3.63 ±â€Š1.36 mm, 3.46 ±â€Š1.31 mm, 3.38 ±â€Š1.24 mm, and 1.87 ±â€Š0.88 for L1 to L5, respectively. The medial branch of the dorsal ramus is enclosed in a fibro-osseous canal bounded by the accessory process, the mammillary process, and the mammilloaccessory ligament.For the percutaneous treatment of block and neurotomy, the first choice of target is the medial branch fibro-osseous canal near to the accessory process. The accessory process is not displayed in x-ray films; therefore, the junction of the superior articular process and the root of the transverse process can be targeted.