Clinical application of artificial intelligence-assisted three-dimensional planning in direct anterior approach hip arthroplasty.

PURPOSE: The objective of this study was to investigate the efficacy of an artificial intelligence-assisted 3D planning system (AIHIP) in total hip arthroplasty by direct anterior approach and assess the reliability of the AIHIP preoperative program in terms of both interobserver and intraobserver agreement. METHODS: A retrospective analysis was conducted on patients who underwent unilateral primary THA via direct anterior approach from June 2019 to March 2022. Participants were randomly assigned to receive either the AIHIP system (n = 220) or the 2D template (control group) (n = 220) for preoperative planning. The primary outcome aimed to evaluate the correspondence between the prosthesis selected intro-operation and the one planned preoperatively, as well as to calculate the intraclass correlation coefficient (ICC). Secondary outcomes included operation time, intraoperative blood loss, fluoroscopy times, Harris hip score (HHS), lower limb length difference (LLD), femoral offset (FO), and bilateral femoral offset difference. RESULTS: No significant differences were observed in gender, age, body mass index (BMI), aetiology, and American Society of Anesthesiologists (ASA) score between the two groups. Both planning methods exhibited good intraobserver agreement for component planning (ICC: 0.941-0.976). Interobserver agreement for component planning was comparable between the two methods (ICC: 0.882-0.929). In the AIHIP group, the accuracy of acetabular cup and femoral stem prosthetics planning significantly improved, with accuracies within the size range of ± 0 and ± 1 being 76.8% and 90.5% and 79.5% and 95.5%, respectively. All differences between two groups were statistically significant (p < 0.05). Patients receiving AIHIP preoperative planning experienced shorter operation times, reduced intraoperative blood loss, fewer fluoroscopy times, and lower leg length discrepancy (LLD) (p < 0.05). Moreover, they demonstrated a higher Harris hip score (HHS) at three days post-surgery (p < 0.05). However, no significant differences were found in femoral offset (FO), difference of bilateral femoral offsets, and HHS at 1 month after the operation. CONCLUSION: Utilizing AIHIP for preoperative planning of direct anterior approach THA can significantly enhance the accuracy of prosthetic sizing with good reliability, decrease operation time, reduce intraoperative blood loss, and more effectively restore the length of both lower limbs. This approach has greater clinical application value.

Mechanism of Artemisia annua L. in the treatment of acute myocardial infarction: network pharmacology, molecular docking and in vivo validation.

This study was to evaluate the potential mechanism of action of Artemisia annua L. (A. annua) in the treatment of acute myocardial infarction (AMI) using network pharmacology, molecular docking and in vivo experiments. 22 active chemical compounds and 193 drug targets of A. annua were screened using the Traditional Chinese Medicine System Pharmacological (TCMSP) database. 3876 disease targets were also collected. Then 158 intersection targets between AMI and A. annua were obtained using R 4.2.0 software. String database was used to construct the protein-protein interaction (PPI) network and 6 core targets (MAPK1, TP53, HSP90AA1, RELA, AKT1, and MYC) were screened. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the R package. GO enrichment results were mainly related to cell responses to chemical stress and cell membrane microregions. KEGG pathways were mainly involved in lipids, atherosclerosis and fluid shear stress. In addition, molecular docking between A. annua active compounds and core targets showed high binding activity. As for in vivo validation, A. annua extract showed significant effects on improving post-infarction ventricular function, delaying ventricular remodeling, and reducing myocardial fibrosis and apoptosis. This study has revealed the potential components and molecular mechanisms of A. annua in the treatment of AMI. Our work also showed that A. annua has great effect on reducing myocardial fibrosis and scar area after infarction.

Independent-effect comparison of five crosslinking procedures for Progressive Keratoconus based on Keratometry and the ABCD Grading System using Generalized Estimating Equations (GEE).

PURPOSE: Corneal collagen crosslinking (CXL) is an effective treatment for progressive keratoconus. Multiple CXL modalities are clinically available. The present study compared the 1 year outcomes of five types of CXL procedures for progressive keratoconus in a Chinese population using generalized estimating equations (GEE). METHODS: This retrospective study included 239 eyes in 171 patients with keratoconus who underwent CXL and were followed up for 1 year. Five CXL procedures were assessed, including Accelerated Transepithelial CXL, Iontophoresis CXL for 10 min, CXL plus phototherapeutic keratectomy (CXL-plus-PTK), High-Fluence Accelerated CXL, and Accelerated CXL. Patients treated with the Accelerated CXL procedure represented the reference group. Primary outcomes were visual acuity change, spherical equivalence, endothelial cell density, mean keratometry (Kmean), maximum keratometry (Kmax), minimum corneal thickness (MCT), and the ABCD Grading System, consisting of A (staging index for ARC; ARC = anterior radius of curvature), B (staging index for PRC, PRC = posterior radius of curvature), and C (staging index for MCT) values 1 year postoperatively compared to baseline. Secondary outcomes were corrected GEE comparisons from each procedure versus the Accelerated CXL group. RESULTS: The Accelerated Transepithelial CXL group had lower performance than the Accelerated CXL group according to Kmean and Kmax. The CXL-plus-PTK group performed significantly better than the reference group as reflected by Kmax (ß = -0.935, P = 0.03). However, the CXL-plus-PTK group did not perform as well for B and C, and the Iontophoresis CXL group performed better for C. CONCLUSIONS: The CXL-plus-PTK procedure was more effective than the Accelerated CXL procedure based on Kmax, and the Iontophoresis CXL procedure performed better on the C value based on the ABCD Grading System.

Impact of local steroid application on dysphagia after anterior cervical spine surgery: a meta-analysis.

INTRODUCTION: Dysphagia is one of the most common complications of anterior cervical spine surgery. Local steroid was widely used to reduce the postoperative swallowing pain. However, the effect of local steroid application on dysphagia after anterior cervical spine surgery was still uncertain. MATERIALS AND METHODS: We searched Medline (PubMed), Embase and the Cochrane Library on July 27, 2021 for studies investigating the effect of local steroid application on dysphagia after anterior cervical spine surgery from their date of inception to 2021. The relative risk or weighted mean difference with 95% confidence interval was recorded as a summary statistic consist of postoperative dysphagia, swallowing VAS scores, SWAL-QOL scores, PSTSI, and steroid related complications. RESULTS: This meta-analysis included 7 RCT studies involving 254 patients in the steroid group and 232 patients in the placebo group. Results showed local steroid group had less patients with dysphagia, lower swallowing VAS scores and less severe of prevertebral soft-tissue edema on the fourth day after surgery. No significant difference in non-fusion rate between the two groups was observed. And all included studies had no serious steroid related complications reported. CONCLUSIONS: The use of local steroid in anterior cervical spine surgery could reduce the early postoperative dysphagia without serious steroid related complication. However, the safety of local steroid application still need further studies with larger samples.

[Exploration of the theory of "Fei and Dachang being interior-exteriorly related" from observing changes of inflammatory cytokines and oxygen free radicals in the lung tissue of ulcerative colitis rats].

OBJECTIVE: To explore the theory of "Fei and Dachang being interior-exteriorly related" and the pathogenesis of lung injury by observing changes of inflammatory cytokines and oxygen free radicals in ulcerative colitis (UC) rats. METHODS: Totally 50 healthy male Wistar rats were randomly divided into two groups, the normal control group and the model group, 25 rats in each group. The UC model was established by allergizing colon mucosa combined with TNBS-alcohol (50%) enema. Another 25 rats were recruited as the normal control group. At week 2 and 4 after modeling, the pathomorphological changes of the lung were observed. Furthermore, the contents of tumor necrosis factor alpha (TNF-alpha) and IL-1beta were determined by ELISA. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) were evaluated with colorimetry. RESULTS: Compared with the normal control group, the pathomorphology of the lung tissue in the model group appeared abnormal at week 2 and 4. Compared with the normal control group, levels of TNF-alpha, IL-1beta, and MDA in the lung tissue significantly increased in the model group (P < 0. 01) and the activities of SOD significantly decreased (P < 0.05, P < 0.01). CONCLUSION: TNF-alpha, IL-1beta, SOD, and MDA might be common material bases for the large intestine involved in lung disease of UC patients, thus providing a modern scientific basis for the theory of Fei and Dachang being interior-exteriorly related.

[Association of MK2 gene polymorphisms with low-density lipoprotein cholesterol and tumor necrosis factor-alpha in Uygur population from Hetian area of Xinjiang].

OBJECTIVE: To investigate the association of MK2 gene with low density lipoprotein cholesterol (LDL-C) and tumor necrosis factor-alpha (TNF-Α) between different gender in Xinjiang Uygur population. METHODS: A total of 350 Uygur males and 595 females were recruited randomly from Hetian area. Two single nucleotide polymorphisms (44890c/t, rs 45514798) in MK2 gene were selected and genotyped by Taqman-PCR in these subjects. All subjects underwent questionnaire-based survey, physical examination, measurement of lipid profiles and plasma TNF-Α determination. RESULTS: Among the male subjects, the concentration of total cholesterol (TC) [TT vs. CT vs. CC: (4.35±1.20) mmol/L vs. (4.69±1.34) mmol/L vs. (4.83±1.44) mmol/L, P=0.033]and TNF-Α [TT vs.CT vs.CC: (106.63±62.39) ng/dL vs. (128.44±86.15) ng/dL vs. (153.06±82.99) ng/dL, P=0.001]were significantly different in 3 genotypes of 44890c/t. However, the LDL-C levels in TT, CT, and CC genotypes of 44890c/t were not different neither in males nor in females [males: (2.64±1.16) mmol/L vs. (2.81±1.28) mmol/L vs. (3.04±1.32) mmol/L, P>0.05; females: (2.42±1.11) mmol/L vs. (2.36±0.99) mmol/L vs. (2.43±1.05) mmol/L, P>0.05]. None of the allele and genotype frequencies of 44890c/tand rs 45514798 were different between high LDL-C group and control group. Linear regression analysis indicated that body mass index (BMI) (beta=0.089) and TNF-Α (beta=0.092) were significantly associated with LDL-C levels in males (P<0.05), while the age, BMI, and waist/hip ratio with LDL-C levels in females (P<0.05). CONCLUSION: The nucleotide polymorphisms (44890c/t and rs 45514798) in MK2 gene may not be associated with LDL-C in both males and females in the Uygur population in Hetian, Xinjiang.

BMP9-induced osteogenetic differentiation and bone formation of muscle-derived stem cells.

Efficient osteogenetic differentiation and bone formation from muscle-derived stem cells (MDSCs) should have potential clinical applications in treating nonunion fracture healing or bone defects. Here, we investigate osteogenetic differentiation ability of MDSCs induced by bone morphogenetic protein 9 (BMP9) in vitro and bone formation ability in rabbit radius defects repairing model. Rabbit's MDSCs were extracted by type I collagenase and trypsin methods, and BMP9 was introduced into MDSCs by infection with recombinant adenovirus. Effects of BMP9-induced osteogenetic differentiation of MDSCs were identified with alkaline phosphatase (ALP) activity and expression of later marker. In stem-cell implantation assay, MDSCs have also shown valuable potential bone formation ability induced by BMP9 in rabbit radius defects repairing test. Taken together, our findings suggest that MDSCs are potentiated osteogenetic stem cells which can be induced by BMP9 to treat large segmental bone defects, nonunion fracture, and/or osteoporotic fracture.

A novel consistency-based training strategy for seizure prediction.

BACKGROUND: Early prediction of epilepsy seizures can warn the patients to take precautions and improve their lives significantly. In recent years, deep learning has become increasingly predominant in seizure prediction for its outstanding performance. With the aim of predicting unseen seizures, it is essential to guarantee the generalization ability of the model, especially considering the non-stationary nature of EEG and the scarcity of seizure events in EEG recordings. Stability training against extra perturbations is an intuitive and effective way to improve the model's ability to generalize. Though a great number of deep learning methods have been developed for seizure prediction, their strategies to increase generalization performance focus on improving the model's architecture itself, and few of them pay attention to the stability of the model against small perturbations. NEW METHOD: In this study, we propose a novel consistency-based training strategy to address this issue. The proposed strategy underlines that a robust model should maintain consistent results for the same input under extra perturbations. Specifically, during training, we use stochastic augmentations to make the input vary from iteration to iteration and consider the output as a stochastic variable. Then a consistency constraint is constructed to penalize the difference between the current output and previous outputs. In this way, the generalization ability of the model will be fully enhanced. RESULTS: To better verify the effectiveness of our proposed strategy, we implement it in two state-of-the-art models with public-available codes, including STFT CNN and Multi-view CNN. Notably, we compare with the first baseline on a scalp EEG dataset and the other on an intracranial EEG dataset. The results show that our strategy could improve the performance significantly for both of them. COMPARISON WITH EXISTING METHODS: Our strategy has increased the sensitivity by 7.1% and reduced the false prediction rate by 0.12/h on the first baseline while improving the AUC by 0.020 on the second baseline. CONCLUSIONS: This study is easy to implement, providing a new solution to enhance the performance of seizure prediction.

Semisupervised Seizure Prediction in Scalp EEG Using Consistency Regularization.

Early prediction of epilepsy seizures can warn the patients to take precautions and improve their lives significantly. In recent years, deep learning has become increasingly predominant in seizure prediction. However, existing deep learning-based approaches in this field require a great deal of labeled data to guarantee performance. At the same time, labeling EEG signals does require the expertise of an experienced pathologist and is incredibly time-consuming. To address this issue, we propose a novel Consistency-based Semisupervised Seizure Prediction Model (CSSPM), where only a fraction of training data is labeled. Our method is based on the principle of consistency regularization, which underlines that a robust model should maintain consistent results for the same input under extra perturbations. Specifically, by using stochastic augmentation and dropout, we consider the entire neural network as a stochastic model and apply a consistency constraint to penalize the difference between the current prediction and previous predictions. In this way, unlabeled data could be fully utilized to improve the decision boundary and enhance prediction performance. Compared with existing studies requiring all training data to be labeled, the proposed method only needs a small portion of data to be labeled while still achieving satisfactory results. Our method provides a promising solution to alleviate the labeling cost for real-world applications.

Pediatric Seizure Prediction in Scalp EEG Using a Multi-Scale Neural Network With Dilated Convolutions.

Objective: Epileptic seizure prediction based on scalp electroencephalogram (EEG) is of great significance for improving the quality of life of patients with epilepsy. In recent years, a number of studies based on deep learning methods have been proposed to address this issue and achieve excellent performance. However, most studies on epileptic seizure prediction by EEG fail to take full advantage of temporal-spatial multi-scale features of EEG signals, while EEG signals carry information in multiple temporal and spatial scales. To this end, in this study, we proposed an end-to-end framework by using a temporal-spatial multi-scale convolutional neural network with dilated convolutions for patient-specific seizure prediction. Methods: Specifically, the model divides the EEG processing pipeline into two stages: the temporal multi-scale stage and the spatial multi-scale stage. In each stage, we firstly extract the multi-scale features along the corresponding dimension. A dilated convolution block is then conducted on these features to expand our model's receptive fields further and systematically aggregate global information. Furthermore, we adopt a feature-weighted fusion strategy based on an attention mechanism to achieve better feature fusion and eliminate redundancy in the dilated convolution block. Results: The proposed model obtains an average sensitivity of 93.3%, an average false prediction rate of 0.007 per hour, and an average proportion of time-in-warning of 6.3% testing in 16 patients from the CHB-MIT dataset with the leave-one-out method. Conclusion: Our model achieves superior performance in comparison to state-of-the-art methods, providing a promising solution for EEG-based seizure prediction.

A novel analysis of Scheimpflug total corneal refractive power following corneal cross-linking in mild to moderate keratoconus.

AIM: To detect an earlier improvement in mild to moderate keratoconus following corneal cross-linking (CXL) with total corneal refractive power (TCRP) using ray tracing method. METHODS: A total of 40 eyes of 30 consecutive patients who underwent CXL for progressive keratoconus were retrospectively enrolled. The following keratometric parameters provided by Pentacam HR, including maximum keratometry (Kmax), steepest keratometry (Ksteep), 3 mm zonal TCRP centered over corneal apex (TCRPapex,zone 3 mm), zonal mean keratometry and TCRP centered over corneal cone (Kmcone,zone and TCRPcone,zone 1, 2, 3 mm) were evaluated preoperatively and 1, 3, 6, and 12mo postoperatively. Groups 1 and 2 were defined based on Kmax at postoperative 1mo as improved (the initial improvement group) or worsen (the initial deterioration group) compared to the preoperative level. RESULTS: In the overall group, only keratometric parameters based on ray tracing method displayed significant improvement early at 3mo postoperatively, in which TCRPcone,zone 1 mm and 2 mm exhibited the largest flattening (0.57 D and 0.53 D, respectively). In Group 1, only Kmax, Kmcone,zone 2 mm and TCRPcone,zone 2 mm showed significant improvement initially at 1mo postoperatively, in which Kmax exhibited the largest improvement (1.05 D), followed by TCRPcone,zone 2 mm (0.82 D). In Group 2, only keratometric parameters based on ray tracing method and Kmcone,zone 3 mm showed slight but not significant improvement early at 3mo, in which TCRPcone,zone 3 mm displayed the most improvement (0.19 D), followed by TCRPcone,zone 2 mm (0.15 D). CONCLUSION: The findings indicate that a 2 mm zonal TCRP centered over Kmax could earlier detect keratometric improvement by CXL compared to other commonly used parameters in mild to moderate keratoconic eyes.

[Negative association of STAMP2 gene polymorphisms with essential hypertension in Xinjiang Uygur population].

OBJECTIVE: To investigate the relationship between the genetic polymorphisms of the six transmembrane protein of prostate 2 gene (STAMP2) and essential hypertension in Xinjiang Uygur population. METHODS: The sequences of STAMP2 gene functional region were sequenced in Xinjiang Uygur population with hypertension. The representative variations selected were genotyped by TaqMan-PCR method in 2047 Uygur individuals, including 810 patients with hypertension and 1237 healthy subjects. The association of the genetic variations of the STAMP2 gene with hypertension in Uygur was analyzed. RESULTS: In the three representative variations (rs8122, rs1981529 and rs34741656) genotyped, there were no significant differences in genotype distribution and allele frequencies between the essential hypertension and control groups (P > 0.05). In ANCOVA analysis, none of the polymorphisms was significantly associated with systolic blood pressure and diastolic blood pressure (P > 0.05). There were no significant differences in haplotype frequencies between the two groups either(P > 0.05). CONCLUSION: There was no association of the three polymorphisms (rs8122, rs1981529 and rs34741656) in the STAMP2 gene with essential hypertension in Xinjiang Uygur population.

[Epidemiological survey of lipid levels and factors in Kazakan people over 30-year old in Fukang of Xinjiang].

OBJECTIVE: To study the lipids level in Kazakan individuals over 30-year-old in Fukang area of Xinjiang. METHODS: Random cluster multistage sampling method were performed to select the subjects, and 991 individuals aged older than 30 from Fukang of Xinjiang were included. The plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), plasma glucose and insulin were measured. Related adverse cardiovascular risk factors were discussed. RESULTS: The mean plasma TC, TG, HDL-C and LDL-C of Kazakan residents over 30-year-old in Fukang of Xinjiang were (5.05 ± 1.07), (1.10 ± 0.66), (1.46 ± 0.38) and (3.06 ± 0.84) mmol/L, respectively. TC, TG and LDL-C levels in male subjects were higher than those in females (male vs female: TC: (5.19 ± 1.05) mmol/L vs (4.94 ± 1.07) mmol/L, t = 3.57, P < 0.01; TG: (1.32 ± 0.80) mmol/L vs (0.94 ± 0.46) mmol/L, t = 8.63, P < 0.01; LDL-C: (3.30 ± 0.85) mmol/L vs (2.88 ± 0.79) mmol/L, t = 8.06, P < 0.01). While the HDL-C level in male subjects was lower than that of female (male vs female: (1.32 ± 0.33) mmol/L vs (1.57 ± 0.38) mmol/L, t = 11.48, P < 0.01). The prevalence of dyslipidemia was 28.3% (280/991) in the overall populations. In the overall populations, the prevalence of hypercholesteremia, hypertriglyceridemia, high low-density lipoprotein cholesterolemia and low serum high density lipoprotein cholesterolemia were 12.6% (125/991), 6.6% (65/991), 11.0% (109/991) and 10.1% (100/991), respectively. The prevalence of individuals with borderline-high TC, TG and LDL-C were 27.0% (268/991), 7.6% (75/991) and 20.5% (203/991), respectively. The prevalence of dyslipidemia was 40.0% (172/430) in male populations. The prevalence of dyslipidemia in group aged 30 - 39, 40 - 49, 50 - 59, 60 and above were 26.2% (78/298), 26.0% (91/350), 31.2% (73/234) and 34.9% (38/109), respectively, the trend of prevalence was significant by trend test for groups comparison (χ(2) = 3.94, P < 0.05). Adjusting for age and gender, TG was positively correlated with waist circumference, abdominal circumference and BMI, the partial relation coefficients were 0.368 (P < 0.01), 0.336 (P < 0.01) and 0.331 (P < 0.01), respectively, and HDL-C was negatively correlated with waist circumference, abdominal circumference and BMI, the partial relation coefficients were -0.340 (P < 0.01), -0.339 (P < 0.01) and -0.321 (P < 0.01), respectively. CONCLUSION: The lipid levels of Kazakan residents from Fukang area are high and are characterized by hypercholesteremia and high low-density lipoprotein cholesterolemia, and more attention of the prevention of dyslipidemia in this populations should be paid to males, border-line abnormal and those aged over 60-year old.

Interpatient ECG Heartbeat Classification with an Adversarial Convolutional Neural Network.

Discovering shared, invariant feature representations across subjects in electrocardiogram (ECG) classification tasks is crucial for improving the generalization of models to unknown patients. Although deep neural networks have recently been emerging in extracting generalizable ECG features, they usually rely on labeled samples from a large number of subjects to guarantee generalization. Extracting invariant representations to intersubject variabilities from a small number of subjects is still a challenge today due to individual physical differences. To address this problem, we propose an adversarial deep neural network framework for interpatient heartbeat classification by integrating adversarial learning into a convolutional neural network to learn subject-invariant, class-discriminative features. The proposed method was evaluated on the MIT-BIH arrhythmia database which is a publicly available ECG dataset collected from 47 patients. Compared with the state-of-the-art methods, the proposed method achieves the highest performance for detecting supraventricular ectopic beats (SVEBs), which are very challenging to identify, and also gains comparable performance on the detection of ventricular ectopic beats (VEBs). The sensitivities of SVEBs and VEBs are 78.8% and 92.5%, respectively. The precisions of SVEBs and VEBs are 90.8% and 94.3%, respectively. With high performance in the detection of pathological classes (i.e., SVEBs and VEBs), this work provides a promising method for ECG classification tasks when the number of patients is limited.

MLBF-Net: A Multi-Lead-Branch Fusion Network for Multi-Class Arrhythmia Classification Using 12-Lead ECG.

Automatic arrhythmia detection using 12-lead electrocardiogram (ECG) signal plays a critical role in early prevention and diagnosis of cardiovascular diseases. In the previous studies on automatic arrhythmia detection, most methods concatenated 12 leads of ECG into a matrix, and then input the matrix to a variety of feature extractors or deep neural networks for extracting useful information. Under such frameworks, these methods had the ability to extract comprehensive features (known as integrity) of 12-lead ECG since the information of each lead interacts with each other during training. However, the diverse lead-specific features (known as diversity) among 12 leads were neglected, causing inadequate information learning for 12-lead ECG. To maximize the information learning of multi-lead ECG, the information fusion of comprehensive features with integrity and lead-specific features with diversity should be taken into account. In this paper, we propose a novel Multi-Lead-Branch Fusion Network (MLBF-Net) architecture for arrhythmia classification by integrating multi-loss optimization to jointly learning diversity and integrity of multi-lead ECG. MLBF-Net is composed of three components: 1) multiple lead-specific branches for learning the diversity of multi-lead ECG; 2) cross-lead features fusion by concatenating the output feature maps of all branches for learning the integrity of multi-lead ECG; 3) multi-loss co-optimization for all the individual branches and the concatenated network. We demonstrate our MLBF-Net on China Physiological Signal Challenge 2018 which is an open 12-lead ECG dataset. The experimental results show that MLBF-Net obtains an average [Formula: see text] score of 0.855, reaching the highest arrhythmia classification performance. The proposed method provides a promising solution for multi-lead ECG analysis from an information fusion perspective.

A short and practical synthesis of oseltamivir phosphate (Tamiflu) from (-)-shikimic acid.

Oseltamivir phosphate (1) was synthesized from (-)-shikimic acid through a short and practical synthetic route via eight steps in 47% overall yield. In addition, the highly regioselective and stereoselective nucleophilic replacement of OMs by the N(3) group in the third and seventh steps has been studied in detail, and the reaction conditions were optimized.

High-temperature Requirement Protein A1 Regulates Odontoblastic Differentiation of Dental Pulp Cells via the Transforming Growth Factor Beta 1/Smad Signaling Pathway.

INTRODUCTION: Dentinogenesis includes odontoblast differentiation and extracellular matrix maturation as well as dentin mineralization. It is regulated by numerous molecules. High-temperature requirement protein A1 (HtrA1) plays crucial roles in bone mineralization and development and is closely associated with the transforming growth factor beta (TGF-ß) signal in osteogenesis differentiation. Simultaneously, the TGF-ß1/small mother against decapentaplegic (Smad) signaling pathway is an important signaling pathway in various physiological processes and as a downstream regulation factor of HtrA1. However, the role of HtrA1 and its relationship with the TGF-ß1/Smad signaling pathway in dentin mineralization is unknown. METHODS: We detected the role of HtrA1 and its relationship with the TGF-ß1/Smad signaling pathway in odontoblastic differentiation of human dental pulp cells (hDPCs) in this study. First, hDPCs were cultured in mineralized medium, and odontoblastic differentiation was confirmed by investigating mineralized nodule formation, alkaline phosphatase (ALP) activity, and the expression of mineral-associated genes, including ALP, collagen I, and dentin sialophosphoprotein. Then, the expression of HtrA1 and TGF-ß1/Smad in hDPCs was investigated in hDPCs during mineralized induction. After HtrA1 knockdown by lentivirus, the mineralized nodule formation, ALP activity, and expression of mineral-associated genes and TGF-ß1/Smad genes were investigated to confirm the effect of HtrA1 on odontoblastic differentiation and its relationship with the TGF-ß1/Smad signaling pathway. RESULTS: The expression of HtrA1 and TGF-ß1 was increased during odontoblastic differentiation of hDPCs along with the messenger RNA expression of downstream factors of the TGF-ß1/Smad signaling pathway. In addition, lentivirus-mediated HtrA1 knockdown inhibited the process of mineralization and the expression of HtrA1 and TGF-ß1/Smad genes. CONCLUSIONS: These findings suggest that HtrA1 might positively regulate odontoblastic differentiation of hDPCs through activation of the TGF-ß1/Smad signaling pathway.

A new flavane acid from the fruits of Illicium verum.

A new compound, illiciumflavane acid (1), along with 13 known compounds (2-14), were isolated from the fruits of Illicium verum Hook. F. Their structures were elucidated through various spectroscopic methods, including 1D NMR ((1)H NMR, (13)C NMR), 2D NMR (HMQC, HMBC and NOESY) and HRMS. The stereochemistry at the chiral centres was determined using CD spectrum as well as analyses of coupling constants and optical rotation data. Cytotoxicity evaluation of four compounds showed that illiciumflavane acid and (E)-1,2-bis(4-methoxyphenyl)ethene exhibited potential against A549 activities with IC50 values of 4.63 µM and 9.17 µM, respectively.

The mobilization of autologous bone marrow stem cells in the treatment of heart failure with Chinese medicine.

Heart failure (HF) is a severe heart disease. The use of autologous bone marrow stem cells (BMCs) mobilization in the treatment of HF has been a hot topic to research both in Western medicine and Chinese medicine (CM). There are many clinical trials and experiments on study of BMCs mobilization for HF therapy, including integrative medicine. The effect of BMCs mobilization is favorable for cardiac repair, while some advantages of CM support the advanced study of its application in BMCs mobilization to treat HF. In addition, with mechanisms of autologous BMCs mobilization for the treatment of HF that will be revealed in the future, especially stem cells niches, integrative medicine would play an important role in this clinical thought of therapy model gradually. Simultaneously, CM should adapt the new approaches of stem cells progresses on HF treatment as holding characteristics of itself.