Exploring the Efficacy Enhancement Mechanism of Qixue Shuangbu prescription after TCM processing for treating chronic heart failure by regulating ERK/Bcl-2/Bax/Caspases-3 signaling pathway.

Qixue Shuangbu prescription (QSP) has been used for the treatment of chronic heart failure (CHF) with remarkable curative effect. Processed QSP (PQSP) could significantly improve the treatment of CHF after traditional Chinese medicine (TCM) processing. This study elucidated the underlying efficacy enhancement mechanism of QSP after TCM processing for treating CHF in vitro and in vivo. The injury of rat cardiomyoblast H9c2 cells was induced by anoxia/reoxygenation to mimic CHF state in vitro. Sixty Sprague-Dawley rats were used to established CHF model by intraperitoneally injecting doxorubicin (the accumulative dose 15 mg/kg). Biochemical examinations were performed in serum and cellular supernatant, respectively. Cardiac functions and histopathological changes were evaluated in CHF model rats. The protein and mRNA levels of ERK1/2, Bcl-2, Bax and Caspase-3 were evaluated by Western blot and RT-PCR, respectively. All above results of low dose crude QSP-treated group (L-CQSP), high dose CQSP-treated group (H-CQSP), low dose PQSP-treated group (L-PQSP), high dose PQSP-treated group (H-PQSP) were compared to systematically explore correlations between TCM processing and the efficacy enhancement for treating CHF of PQSP. Compared with the model group, the L-CQSP group showed significant improvement in cardiac function at 8th weeks, while no significant improvement in cardiomyocyte apoptosis and fibrosis. Both H-CQSP, L-PQSP and H-PQSP exerted beneficial therapeutic effects in injured H9c2 cardiomyocytes and CHF model rats. L-PQSP and H-PQSP significantly increased cell viability and the activity of SOD, decreased the activities of LDH, MDA and NO, up-regulated the expression of ERK1/2 and Bcl-2, down-regulated the expression of Bax and Caspase-3 compared to the same dosage of CQSP. The efficacy enhancement mechanism of PQSP after TCM processing for treating CHF was directly related to the regulation of ERK/Bcl-2/Bax/Caspases-3 signaling pathway.

A comprehensive clinical evaluation of HER2-TKIs in patients with previously treated HER2-positive metastatic breast cancer.

Human epidermal growth factor receptor 2-tyrosine kinase inhibitors (HER2-TKIs) have been extensively utilized for treating HER2-positive metastatic breast cancer (MBC), with numerous clinical trial reports available. We aim to systematically perform a comprehensive clinical evaluation on HER2-TKIs, provide a reference for the clinical rational use of drugs, and serve for the decision-making of the national drug policy. We performed comprehensive clinical evaluation in six dimensions including safety, effectiveness, economy, suitability, accessibility, and innovation through meta-analysis, literature review, drug administration websites, and other relevant medication data to analyze HER2-TKIs in treating HER2-positive MBC. For safety, the risk of ≥ grade 3 adverse events among pyrotinib, lapatinib, and neratinib is not significantly different. Furthermore, pyrotinib and neratinib were found to be higher in the risk of ≥ grade 3 diarrhea than lapatinib, however the risk could be reversed and prevented with loperamide. Regarding effectiveness and economy, pyrotinib was confirmed to have the best efficacy and cost-utility value, neratinib the second, and lapatinib the third. As regards innovation and suitability, pyrotinib showed better than other HER2-TKIs. In addition, pyrotinib received a higher recommendation than other HER2-TKIs in patients with HER2-positive MBC. The accessibility of pyrotinib was found to be the best with better urban, rural, and national affordability and lower annual treatment costs. Pyrotinib is more valuable in clinics with better safety, effectiveness, economy, suitability, accessibility, and innovation in HER2-positive MBC. This study could provide references for the clinical application of HER2-TKIs in treating HER2-positive MBC.

Red phosphorus encapsulated in 3D N-doped porous carbon nanofibers: an enhanced sodium-ion battery anode material.

We report a sodium-ion battery anode design using red phosphorus encapsulated in nitrogen-doped porous carbon nanofibers that mitigates volume expansion and poor conductivity issues, enhancing battery performance. Density functional theory calculations suggest nitrogen doping promotes robust phosphorus interactions, and finite element analysis indicates the design controls volume expansion.

Construction of a Metal-Silica Interface for Semihydrogenation of Alkynes.

Fabricating optimum surface structures represents an attractive approach for synthesizing supported catalysts with high activity and specific selectivity. New active sites could be flexibly constructed via the strong metal-support interaction under the redox condition. Herein, we demonstrated the formation of a new Rh-Si surface on a silica-modified carbon nanotube supported Rh catalyst under the high-temperature reduction condition as well as a thin amorphous silica coating layer and weak chemisorption toward the CO molecule. The electronic interactions between Rh and Si, along with the particular structure, guarantee desirable catalytic performance for the semihydrogenation of phenylacetylene under mild conditions. This facile approach might be extensively used in constructing new active sites with robust activity and specific selectivity in diverse heterogeneous catalysis systems.

Comparative pharmacokinetics of 11 major bioactive components between two dosage forms of Qixue Shuangbu Prescription in rats by ultra-high-performance liquid chromatography-tandem mass spectrometry.

Although Qixue Shuangbu Prescription (QSP) is a classic Chinese medicine prescription for treating chronic heart failure. Low bioavailability due to the insolubility and poor biofilm permeability of the main bioactive ingredients of QSP is still a key factor limiting its efficacy. In this study, a novel self-microemulsifying drug delivery system was proposed to effectively improve the bioavailability of QSP. The qualified ultra-high-performance liquid chromatography-tandem mass spectrometry methodology was established to investigate the pharmacokinetics characteristics of the QSP self-microemulsifying drug delivery system. Our results showed that 11 components in the self-microemulsifying drug delivery system group had prolonged T1/2 and MRT0-t values compared with QSP extract. The Cmax of calycosin-7-glucoside (CG), vanillic acid and paeoniflorin increased 2.5 times, 2.4 times and 2.3 times, respectively. The relative bioavailability values of CG, paeoniflorin and ononin were most significantly affected, increasing by 383.2%, 336.5% and 307.1%, respectively. This study promoted the development of new dosage forms of QSP and provided a useful reference for improving dosage forms to solve the problem of low bioavailability of traditional Chinese medicine.

Unveiling changes in the complexation of dissolved organic matter with Pb(II) by photochemical and microbial degradation using fluorescence EEMs-PARAFAC.

Dissolved organic matter (DOM) is very important in determining the speciation, behaviors, and risk of metal pollutants in aquatic ecosystems. Photochemical and microbial degradation are key processes in the cycling of DOM, yet their effects on the DOM-Pb(II) interaction remain largely unknown. This was studied by examining the complexation of river DOM with Pb(II) after degradation, using fluorescence quenching titration and excitation-emission matrices-parallel factor analysis (EEMs-PARAFAC). Three humic-like and two protein-like components were identified, with strong removals of humic-like components and decreasing average molecular weight and humification degree of DOM by photo- and photo-microbial degradation. The changes in humic-like abundance and structure resulted in notable weakening of their interaction with Pb(II). The tryptophan-like C2 was also mainly removed by photo-degradation, while the tyrosine-like C3 could be either removed or accumulated. The Pb(II)-binding of protein-like components was generally weaker but was enhanced in some degradation groups, which might be related to the lowering competition from humic-like components. The binding parameters correlated significantly with the DOM indices, which were dominated by photo-degradation for humic-like components but by seasonal variations for the tyrosine-like component. These results have implications for understanding the key mechanisms underlying the variability of the DOM-metal interaction in aquatic environments.

Comparative pharmacokinetics of four bioactive components in normal and chronic heart failure rats after oral administration of Qiangxin Lishui Prescription by microdialysis combined with ultra-high-performance liquid chromatography.

Qiangxin Lishui Prescription (QLP) has been clinically applied for treating heart failure with remarkable curative effects. A multi-component pharmacokinetic research is very necessary for determining active substances in it. This study aims to profile the traits and differences in the pharmacokinetics of salvianolic acid B, astragaloside IV, calycosin-7-O-ß-D-glucoside and kaempferol in QLP between normal and chronic heart failure (CHF) rats by microdialysis combined with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Sensitive, selective, and online microdialysis combined with the UHPLC-MS/MS method was successfully established and applied to study the pharmacokinetics of QLP. The pathological condition of CHF could lead to the enhancement of systematic exposure and reduction of the metabolic rate of four bioactive components for better bioavailability and therapeutic efficacy. The pharmacokinetic results will provide data support for the clinical application of QLP.

Synergistic mechanism of processing method for Qixue Shuangbu prescription in the treatment of chronic heart failure based on plasma metabolomics-Systematic bioinformatics.

Previous clinical studies have found that the efficacy of processed Qixue Shuangbu Prescription has been significantly improved in the treatment of chronic heart failure. However, the absorbed constituents and synergistic mechanisms of processed Qixue Shuangbu Prescription to enhance the therapeutic effect of chronic heart failure remain unclear. In this study, we propose an integrated strategy combining plasma metabolomics, network pharmacology, and molecular docking to study the absorbed constituents and synergistic mechanisms of processed Qixue Shuangbu Prescription. A total of 34 prototype constituents and 24 metabolites were identified in rat plasma after administration of crude and processed Qixue Shuangbu Prescription. As a result, six potential absorbed constituents and six potential targets for the treatment of chronic heart failure were identified. In addition, the result of molecular docking indicated that the key constituents exhibited good affinity to hub targets. This study showed that the multiomics approach could effectively clarify absorbed constituents and synergistic mechanisms of traditional Chinese medicine processing from a new perspective.

Identification and quality evaluation of different processed products of Aconitum carmichaelii by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry and ultra-high-performance liquid chromatography-tandem mass spectrometry.

Aconitum carmichaelii is widely used to treat chronic and intractable diseases due to its remarkable curative effect, but it is also a highly toxic herb with severe cardiac and neurotoxicity. It has been combined with honey for thousands of years to reduce toxicity and enhance efficacy, but there has been no study on the chemical constituent changes in the honey-processing so far. In this study, the chemical constituents of A. carmichaelii before and after honey-processing were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. The results showed that a total of 118 compounds were identified, of which six compounds disappeared and five compounds were newly produced after honey-processing, and the cleavage pathway of main components was elucidated. At the same time, 25 compounds were found to have significant effects on different products, among which four compounds with the biggest difference were selected for quantitative analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry. This study not only explained the chemical differences between the different products, but also helped to control the quality of the honey-processed products more effectively, and laid a foundation for further elucidating the mechanism of chemical constituent change during the honey-processing of A. carmichaelii.

Comparative pharmacokinetics of seven bioactive components after oral administration of crude and processed Qixue Shuangbu Prescription in chronic heart failure rats by microdialysis combined with UPLC-MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Qixue Shuangbu Prescription (QSP) is a classical traditional Chinese medicine prescription, which has widely used for the treatment of chronic heart failure (CHF). Preliminary clinical studies have shown that the efficacy of processed QSP (P-QSP) in treating CHF is greater than crude QSP (C-QSP). However, the pharmacokinetic characteristics of its major bioactive components under pathological conditions are unclear. AIM OF STUDY: This study aims to compare pharmacokinetics of seven bioactive components after oral administration of C-QSP and P-QSP in CHF model rats. MATERIALS AND METHODS: Ginsenoside Rb1, ginsenoside Re, ginsenoside Rg1, ferulic acid, astragaloside IV, calycosin-7-O-ß-D-glucoside, and paeoniflorin in QSP were used as the target components. CHF model in rats was induced by the intraperitoneal injection of doxorubicin. A microdialysis combined with UPLC-MS/MS method was first established to compare the pharmacokinetics of seven major bioactive components in CHF model rats after oral administration of C-QSP and P-QSP. RESULTS: This method was successfully applied to the pharmacokinetic investigation of seven major components of C-QSP and P-QSP following oral administration in CHF model rats. Compared with the C-QSP group, the Cmax, AUC0-t and AUC0-∞ of ginsenoside Rb1, ginsenoside Re, ginsenoside Rg1, ferulic acid, astragaloside IV and paeoniflorin significantly increased (P < 0.05) in the P-QSP group, which suggested that the absorptivity and bioavailability were increased. Lower T1/2, MRT0-t of ginsenoside Rb1, gerulic acid and higher T1/2, MRT0-t of ginsenoside Rb1, astragaloside IV, paeoniflorin in the P-QSP group, which indicated that eliminated more quickly or slowly, respectively. CONCLUSIONS: The pharmacokinetic parameters of bioactive components were significantly changed for better bioavailability and absorption, longer lasting time elimination, which were beneficial for enhancing therapeutic efficacy in the P-QSP group. This study will provide a new perspective to explain the pharmacokinetic-pharmacodynamic correlation of P-QSP on the treatment of CHF.

Changes Observed in Potential Key Candidate Genes of Peripheral Immunity Induced by Tai Chi among Patients with Parkinson's Disease.

Parkinson's disease (PD) is a common progressive neurodegenerative disease characterized by motor dysfunction. Although the inhibition of inflammation by Tai Chi has been demonstrated to involve a peripheral cytokine response and may play an important role in improving the motor function of PD patients, the related specific molecular mechanisms of the peripheral immune response to Tai Chi are not fully understood. The microarray dataset 'GSE124676' for the peripheral immune response to Tai Chi of PD patients was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened and analyzed using weighted gene co-expression network analysis (WGCNA). A total of 136 DEGs were found in the PD patients after Tai Chi, suggesting an effect of Tai Chi on the peripheral immunity of PD patients. The DEGs are mainly involved in neutrophil activation, T-cell activation, and NOD-like receptor and IL-17 signaling pathways. Furthermore, six key candidate genes (FOS, FOSB, JUNB, ZFP36, CAMP and LCN2) that are involved in peripheral inflammation and the inhibition of inflammation induced by Tai Chi were observed. The results in the present study could be conducive to comprehensively understanding the molecular mechanism involved in the effect of Tai Chi on peripheral inflammation in PD patients and providing novel targets for future advanced research.

[Pharmacokinetic study of Polydopamine Guttate Pills loaded with active components of Sarcandrae Herba in rats].

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established for the determination of active components of Sarcandrae Herba, and applied to the pharmacokinetics study of multiple dosage forms. After SD rats were administered by gavage with three dosage forms [Sarcandrae Herba extract, commercial Sarcandrae Herba Guttate Pills, and polydopamine guttate pills loaded with active components of Sarcandrae Herba(PDA-Sg Guttate Pills)], blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC C_(18) column(2.1 mm×100 mm, 1.7 µm). The mobile phase consisted of water containing 0.2% formic acid and acetonitrile in gradient elution. The negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 2.0. All four components could be detected in the plasma of rats in each group at each time point except the neochlorogenic acid and cryptochlorogenic acid in the Sarcandrae Herba extract group. The guttate pills group showed a significant increase in drug content at each time point. The exposure of the main components of Sarcandrae Herba in blood was effectively increased by PDA-drug loading effect in PDA-Sg Guttate Pills(The AUC_(0-24 h) of neochlorogenic acid, cryptochlorogenic acid, isaziridin and rosmarinic acid reached 2.45, 32.90, 1.54, 4.81 times that of the commercial guttate pills). This study proves the measurability of the above-mentioned multi-component in vitro-in vivo delivery process. The pharmacokinetic study has shown that PDA-Sg Guttate Pills can effectively delay the elimination time and improve the bioavailability of the four components, which can provide theoretical data for the production of the drug.

Effect of C1 Single-door Laminoplasty on Symptomatic Atlas Canal Stenosis.

OBJECTIVE: To verify the effect of single-door laminoplasty combined with atlantoaxial fusion in the treatment of symptomatic atlas canal stenosis. METHODS: This is a single-center retrospective analysis. From February 2014 to January 2019, 16 patients (five were females) with an average age of 63.4 years (56-71 years) were enrolled in this study. Patients with compressive cervical myelopathy with CT scan showed an inner sagittal diameter (ISD) of C1 less than 29 mm or C1 canal space available for cord (SAC) of <12 mm were included, while isolated C1 stenosis without myelopathy or isolated C1 stenosis without atlantoaxial subluxation were excluded in this study. All patients underwent continuous heavy-weight skull traction, atlas single-door laminoplasty and atlantoaxial fusion. The differences in the pre- and post-operative inner sagittal diameter, space available for cord, atlas-dens interval (ADI) and compression of the spinal cord were analyzed by using CT and MRI. Functional evaluation was performed by using the Japanese Orthopaedic Association scoring system and the Neck Disability Index scoring system. RESULTS: Single-door laminoplasty provided a full decompression for the spinal cord while retaining the whole posterior arch. No complications were encountered except a superficial wound infection in one patient. At final follow-up, The ADI was significantly reduced from 5.2 ± 1.8 mm to 1.7 ± 0.6 mm after surgery on average (P < 0.05). Average inner sagittal diameter of C1 was increased from 26.3 ± 2.6 mm to 34.9 ± 2.9 mm and the space available for cord was increased from 6 ± 1.7 mm to 17.8 ± 3.6 mm (P < 0.05). Meanwhile, the Japanese Orthopaedic Association (JOA) score of the 16 cases was improved from 11.4 ± 1.8 to 14.1 ± 1.4 on average (P < 0.05). The postoperative neck pain VAS score decreased significantly, from 2.6 ± 1.0 preoperatively to 1.3 ± 0.9 postoperatively (P < 0.05). The influence of neck pain on patient's life was improved from 17.8 ± 3.9 to 13.9 ± 3.3 after surgery (P < 0.05). At the last follow-up, the healing of the hinge fracture and the fusion between atlas and axis were observed in all patients. CONCLUSIONS: Single-door laminoplasty combined with atlantoaxial fusion not only provides enough space for decompression but also offers intact arch for bone grafting, suggesting that it might provide a more feasible method for the correction of symptomatic atlas canal stenosis.

Critical evaluation of the interaction between fluorescent dissolved organic matter and Pb(II) under variable environmental conditions.

Dissolved organic matter (DOM) can strongly influence the behavior and risk of metal pollutants in aquatic ecosystems. However, a comprehensive study on the effects of DOM level and environmental factors on the binding of DOM with Pb(II) is lacking. This study examined the DOM-Pb(II) interaction in the river water under variable DOM level, pH, and major ions, using fluorescence excitation-emission matrices-parallel factor analysis (EEMs-PARAFAC). Four humic-like and one protein-like component were identified, and the abundant humic-like components showed higher Pb(II)-binding fractions (f) than the protein-like component. The f of PARAFAC components decreased while the conditional stability constants (logKM) increased for the diluted DOM, indicating the influence of DOM level on its metal binding. The DOM-Pb(II) interaction was sensitive to changes in pH, with generally higher f and lower logKM at the alkaline condition due to changes in the DOM conformation. The addition of major ions significantly decreased the fluorescence quenching by Pb(II), due to competitive effects and potential DOM conformation changes at elevated ions. Overall, our results show that the DOM-Pb(II) complexation is highly dependent on both the DOM properties and environmental factors, which have implications for optimizing the experimental conditions and for comparing the results in different environments.

Guizhi Fuling Capsule inhibits uterine fibroids growth by modulating Med12-mediated Wnt/ß-Catenin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Guizhi Fuling Capsule (GFC) is a famous traditional Chinese medicine (TCM) formula recorded in Synopsis of the Golden Chamber, which has achieved obvious effects in the treatment of uterine fibroids (UFs). AIM OF STUDY: Mediator complex subunit 12 (Med12) mutations were closely related to UFs in 85% of fibroid cases. The Wnt/ß-Catenin signaling pathway plays an important role in the occurrence and development of UFs. This study aims to explore the pharmacological mechanism of GFC against UFs in which the Med12-mediated Wnt/ß-Catenin pathway is involved. MATERIALS AND METHODS: Med12 was silenced in uterine fibroid cells (UFCs) using a lentivirus-based Med12 gene-specific RNA interference (RNAi) strategy. Cell proliferation was performed by CCK-8 assay, cell apoptosis and cell cycle were measured by flow cytometry. The rat model of UFs was established by injecting estradiol benzoate and progesterone. Forty-eight rats were divided into six groups, the low-dose GFC (L-GFC) group, the medium-dose GFC (M-GFC) group and the high-dose GFC (H-GFC) group were intragastrically treated with GFC solution at 0.25 g/kg, 0.50 g/kg and 1.00 g/kg per day for 8 weeks, the positive control (PC) group was administrated with mifepristone (2.70 mg/kg/day), the normal control (NC) group and the model control (MC) group were given equal volume of normal saline once a day for 8 weeks. The histopathological changes of uterine tissues were evaluated by H&E staining. The expression of Med12 in uterine tissues were detected by immunohistochemistry. The protein and mRNA levels of associated genes were evaluated by western bolt and real time-PCR, respectively. Related indicators involved in Wnt/ß-Catenin pathway, such as Wnt1, ß-Catenin, Cyclin D1, TCF1/TCF7 and C-myc, were compared among different groups. RESULTS: The Wnt/ß-Catenin signaling pathway was inhibited after Med12 gene was knocked out in UFCs. GFC-containing serum could induce cell apoptosis, make the cell cycle stagnated in G0/G1 phase to inhibiting the proliferation and reduce the expression of Wnt1, ß-Catenin, Cyclin D1, TCF1/TCF7, and C-myc in control-shRNA cells, while had no significant effect on Med12-shRNA cells. Compared with the MC group, the weight, endometrial thickness, and pathological structure of the uterus in the GFC treated groups were significantly improved. The expression of Med12, Wnt1, ß-Catenin, Cyclin D1, TCF1/TCF7, and C-myc that related to Wnt/ß-Catenin pathway in the GFC treated groups were decreased with the increase of dosage administration. CONCLUSIONS: GFC inhibited UFs growth, which was directly associated with Med12 modulated Wnt/ß-Catenin signaling pathway. This study provided new perspective to understand the therapeutic mechanism of UFs.

Effects of Processing Method Changes in Main Volatile Compounds of Qixue Shuangbu Prescription by Needle Trap Device Coupled with Gas Chromatography-Triple Quadrupole Mass Spectrometry.

Qixue Shuangbu Prescription (QSP) has been widely applied in the treatment of chronic heart failure (CHF). Previous clinical studies have found that the efficacy of processed QSP was significantly enhanced in the treatment of CHF. We have identified and analyzed the nonvolatile components before and after processing of QSP, and predicted the mechanism of synergistic effect after processing in the treatment of CHF. However, the synergistic mechanism of processed QSP caused by the difference of volatile components was still unclear. In this study, we developed a method of needle trap device coupled with gas chromatography-triple quadrupole mass spectrometry to elucidate the difference of volatile components between crude and processed QSP. The established method has been used to identify 104 volatile compounds in crude and processed QSP. The results of multivariate data showed 38 differential compounds were screened as potential markers, which would further explain the mechanism of processing synergistic effect of processed QSP. This study successfully developed the method to elucidate its processing mechanism based on the difference of volatile compositions between crude and processed QSP for the first time, and it would provide a novel analytical strategy for the impacts of different processing methods on main volatile compounds in traditional Chinese medicine.

Practice of the new supervised machine learning predictive analytics for glioma patient survival after tumor resection: Experiences in a high-volume Chinese center.

Objective: This study aims to assess the effectiveness of the Gradient Boosting (GB) algorithm on glioma prognosis prediction and to explore new predictive models for glioma patient survival after tumor resection. Methods: A cohort of 776 glioma cases (WHO grades II-IV) between 2010 and 2017 was obtained. Clinical characteristics and biomarker information were reviewed. Subsequently, we constructed the conventional Cox survival model and three different supervised machine learning models, including support vector machine (SVM), random survival forest (RSF), Tree GB, and Component GB. Then, the model performance was compared with each other. At last, we also assessed the feature importance of models. Results: The concordance indexes of the conventional survival model, SVM, RSF, Tree GB, and Component GB were 0.755, 0.787, 0.830, 0.837, and 0.840, respectively. All areas under the cumulative receiver operating characteristic curve of both GB models were above 0.800 at different survival times. Their calibration curves showed good calibration of survival prediction. Meanwhile, the analysis of feature importance revealed Karnofsky performance status, age, tumor subtype, extent of resection, and so on as crucial predictive factors. Conclusion: Gradient Boosting models performed better in predicting glioma patient survival after tumor resection than other models.

Anterior Selective Lumbar Fusion Saving More Distal Fusion Segments Compared with Posterior Approach in the Treatment of Adolescent Idiopathic Scoliosis with Lenke Type 5: A Cohort Study with More Than 8-Year Follow-up.

OBJECTIVE: To investigate whether anterior selective fusion (ASF) could save more distal fusion segments compared with posterior approach in the treatment of Lenke type 5 adolescent idiopathic scoliosis with long term follow-up. METHODS: A retrospective cohort study. From 2008 to 2011, 22 AIS girls with Lenke type 5 who underwent ASF or posterior selective fusion (PSF) with more than 8-year follow-up, were extracted from the database. 13 girls in the ASF group had an average age of 14.3 ± 1.3 years and Risser sign of 3.3 ± 1.1; 9 PSF girls had an average age of 16.2 ± 3.6 years and Risser sign of 3.8 ± 1.5. The radiographic outcome was compared between groups preoperatively, 6-month postoperatively, 8-year postoperatively and at last follow-up (>8 years). RESULTS: The average follow-up duration was 8.7 ± 0.4 (ASF) and 8.8 ± 0.5 (PSF) years, respectively. There was no significant difference at baseline in age, Risser sign and preoperative curve pattern in the coronal and sagittal plane between the groups (P > 0.05). The ASF group had significantly shorter fusion segments (5.1 ± 0.6 vs. 7.0 ± 1.3) and decreased upper instrumented vertebra (UIV) (T11 ± 0.8 vs. T10 ± 0.8) than the PSF (P < 0.05); while no significant difference was found in the lower instrumented vertebra (LIV) and distal reserved segments (P > 0.05), which suggested that ASF could shorten the fusion segments by lowering UIV. The distal compensatory curve in the ASF group (9.0° ± 3.9°) was significantly larger than in the PSF group (3.3° ± 2.4°, P = 0.003), despite of no significant difference in the incidence of coronal imbalance (P > 0.05), indicating that both two approaches could obtain satisfactory correction in the coronal plane. In the sagittal plane, PSF patients had significantly larger lumbar lordosis (LL, 59.1° ± 10.5°), thoracic kyphosis (TK, 37.2° ± 13.3°) and proximal junctional angle (PJA, 13.3° ± 6.1°) at the last follow-up than the ASF (LL: 43.4° ± 9.4°; TK: 20.7° ± 8.4°; PJA: 4.7° ± 3.4°; P < 0.05), but without significant difference in proximal junctional kyphosis (PJK) and sagittal vertical axis (SVA) (P > 0.05). After controlling for age, Risser sign, and radiographic parameters related to the primary curve pattern, shorter fusion segments and more distal reserved segments still remained significant in the ASF group with greater Risser sign (P < 0.05). No major intra- or post-operative complications occurred. CONCLUSIONS: Both ASF and PSF could obtain satisfactory coronal and sagittal correction for Lenke 5 AIS; compared with PSF, ASF could shorten the fusion segments by lowering UIV, and save more distal fusion segments only in patients with greater skeletal maturity.

Design, Synthesis and In-Vitro Biological Evaluation of Antofine and Tylophorine Prodrugs as Hypoxia-Targeted Anticancer Agents.

Phenanthroindolizidines, such as antofine and tylophorine, are a family of natural alkaloids isolated from different species of Asclepiadaceas. They are characterized by interesting biological activities, such as pronounced cytotoxicity against different human cancerous cell lines, including multidrug-resistant examples. Nonetheless, these derivatives are associated with severe neurotoxicity and loss of in vivo activity due to the highly lipophilic nature of the alkaloids. Here, we describe the development of highly polar prodrugs of antofine and tylophorine as hypoxia-targeted prodrugs. The developed quaternary ammonium salts of phenanthroindolizidines showed high chemical and metabolic stability and are predicted to have no penetration through the blood-brain barrier. The designed prodrugs displayed decreased cytotoxicity when tested under normoxic conditions. However, their cytotoxic activity considerably increased when tested under hypoxic conditions.

Comparative pharmacokinetics study of six effective components between two dosage forms of Qixue-Shuangbu Prescription in rats by UPLC-MS/MS.

Qixue-Shuangbu Prescription (QSP) is an efficacious prescription for treating heart failure, myocardial ischemia and other diseases. It is composed of nine Chinese herbs. This study investigated and compared the pharmacokinetics of QSP in rats by UPLC-MS/MS between two dosage forms of traditional decoction (TD) and compound tincture (CT). Owing to the complexity of the chemicals in QSP, ginsenoside Rg1, ginsenoside Re, ferulic acid, astragaloside IV, rhein and calycosin were chosen for the pharmacokinetics study. The method established for detecting serum specimens was shown to have acceptable selectivity, linearity, lower limit of quantitation, precision, accuracy, recovery, matrix effect and stability. The peak concentration, AUC0-t and AUC0-∞ of ginsenoside Re, ginsenoside Rg1, ferulic acid and rhein were significantly increased after oral administration of CT (P < 0.05), the half-life of ferulic acid in the CT group was lower than that in the TD group (P < 0.05) and the half-life and AUC0-∞ of astragaloside IV in the CT group were significantly increased (P < 0.05), which revealed that wine-processing could influence the bioavailability and the elimination of these compounds. For better clinical efficacy, we suggest that the CT dosage form of QSP should be selected.