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Objective: To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved, specifically focusing on the role of the caspase-3/gasdermin E (GSDME) signaling pathway and the impact of endoplasmic reticulum (ER) stress and autophagy. Methods: Necrostatin-1 (Nec-1), lactate dehydrogenase release (LDH) assay, and Hoechst/propidium iodide (PI) double staining were employed to validate the mode of cell death. Western blot was used to detect the cleavage of GSDME and the expression of light chain 3 (LC3) and BIP. Results: Celastrol induced cell swelling with large bubbles, which is consistent with the pyroptotic phenotype. Moreover, treatment with celastrol induced GSDME cleavage, indicating the activation of GSDME-mediated pyroptosis. GSDME knockout via CRISPR/Cas9 blocked the pyroptotic morphology of celastrol in HeLa cells. In addition, cleavage of GSDME was attenuated by a specific caspase-3 inhibitor in celastrol-treated cells, suggesting that GSDME activation was induced by caspase-3. Mechanistically, celastrol induced endoplasmic reticulum (ER) stress and autophagy in HeLa cells, and other ER stress inducers produced effects consistent with those of celastrol. Conclusion: These findings suggest that celastrol triggers caspase-3/GSDME-dependent pyroptosis via activation of ER stress, which may shed light on the potential antitumor clinical applications of celastrol.

ObjectivePatient education is an important part of ankylosing spondylitis (AS) management. Effective patient education should be targeted at specific priorities and needs of the patients. However, the educational needs of patients with AS in China have not been systematically explored. The purpose of this study was to assess the level of educational needs and analyze associated factors in patients with AS in China.MethodsThis multicenter cross-sectional study was conducted at five hospitals in China. The Chinese version of the Educational Needs Assessment Tool (ENAT) was used to measure educational needs. Disease activity and physical function were assessed using the Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Multiple linear regression analysis was used to identify the predictors of educational needs.ResultsThis study included 163 patients with AS. The mean ENAT score was 86.25 (31.64). Patients wanted to know more about the arthritis process, self-help measures, and treatments. Multiple linear regression analysis indicated that younger age, being female, higher disease activity, and no family history of AS (p

Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment.

Introduction: Human topoisomerase 1 (TOP1) is an important target of various anticancer compounds. The design and discovery of inhibitors targeting TOP1 are of great significance for the development of anticancer drugs. Evodiamine and thieno [2,3-d] pyridine hybrids show potential antitumor activity. Herein, the anti-gastric cancer activities of these hybrids were investigated.Methods: The inhibitory effects of different concentrations of ten evodiamine derivatives on the gastric cancer cell line SGC-7901 were assessed using a methyl thiazolyl tetrazolium assay. Compounds EVO-1 and EVO-6 strongly inhibited gastric cancer cell proliferation, with inhibition rates of 81.17% ± 5.08% and 80.92% ± 2.75%, respectively. To discover the relationship between the structure and activity of these two derivatives, density functional theory was used to investigate their optimized geometries, natural population charges, frontier molecular orbitals, and molecular electrostatic potentials. To clarify their anti-gastric cancer mechanisms, molecular docking, molecular dynamics simulations, and binding free energy calculations were performed against TOP1.Results: The results demonstrated that these compounds could intercalate into the cleaved DNA-binding site to form a TOP1–DNA–ligand ternary complex, and the ligand remained secure at the cleaved DNA-binding site to form a stable ternary complex. As the binding free energy of compound EVO-1 with TOP1 (−38.33 kcal·mol−1) was lower than that of compound EVO-6 (−33.25 kcal·mol−1), compound EVO-1 could be a more potent anti-gastric cancer agent than compound EVO-6.Discussion: Thus, compound EVO-1 could be a promising anti-gastric cancer drug candidate. This study may facilitate the design and development of novel TOP1 inhibitors.

Isocitrate dehydrogenase 1 (IDH1) is a necessary enzyme for cellular respiration in the tricarboxylic acid cycle. Mutant isocitrate dehydrogenase 1 (mIDH1) has been detected overexpressed in a variety of cancers. mIDH1 inhibitor ivosidenib (AG-120) was only approved by the Food and Drug Administration (FDA) for marketing, nevertheless, a range of resistance has been frequently reported. In this study, several mIDH1 inhibitors with the common backbone pyridin-2-one were explored using the three-dimensional structure–activity relationship (3D-QSAR), scaffold hopping, absorption, distribution, metabolism, excretion (ADME) prediction, and molecular dynamics (MD) simulations. Comparative molecular field analysis (CoMFA, R2 = 0.980, Q2 = 0.765) and comparative molecular similarity index analysis (CoMSIA, R2 = 0.997, Q2 = 0.770) were used to build 3D-QSAR models, which yielded notably decent predictive ability. A series of novel structures was designed through scaffold hopping. The predicted pIC50 values of C3, C6, and C9 were higher in the model of 3D-QSAR. Additionally, MD simulations culminated in the identification of potent mIDH1 inhibitors, exhibiting strong binding interactions, while the analyzed parameters were free energy landscape (FEL), radius of gyration (Rg), solvent accessible surface area (SASA), and polar surface area (PSA). Binding free energy demonstrated that C2 exhibited the highest binding free energy with IDH1, which was −93.25 ± 5.20 kcal/mol. This research offers theoretical guidance for the rational design of novel mIDH1 inhibitors.

The incidence and mortality of lung cancer are on the rise worldwide. However, the benefit of clinical treatment in lung cancer is limited. Owning to important sources of drug development, natural products have received constant attention around the world. Main ingredient polysaccharides in natural products have been found to have various activities in pharmacological research. In recent years, more and more scientists are looking for the effects and mechanisms of different natural product polysaccharides on lung cancer. In this review, we focus on the following aspects: First, natural product polysaccharides have been discovered to directly suppress the growth of lung cancer cells, which can be effective in limiting tumor progression. Additionally, polysaccharides have been considered to enhance immune function, which can play a pivotal role in fighting lung cancer. Lastly, polysaccharides can improve the efficacy of drugs in lung cancer treatment by regulating the gut microbiota. Overall, the research of natural product polysaccharides in the treatment of lung cancer is a promising area that has the potential to lead to new clinical treatments. With better understanding, natural product polysaccharides have the potential to become important components of future lung cancer treatments.

Background: Toxic Euphorbia kansui (EK) is employed to treat malignant ascites effusion (MAE). EK stir-fried with vinegar (VEK) has been demonstrated to reduce toxicity due to its preserved water-expelling effect. This was demonstrated to be correlated with gut microbiota. Therein, bile acids (BAs) have a bidirectional relationship with the gut microbiota. Therefore, the aim of this study is to explore whether BA-mediated gut microbiota influences the water-expelling effect of VEK against MAE.Methods: The MAE rat model was established by intraperitoneal injection of Walker-256 tumor cells. A reliable simultaneous method for the determination of 15 bile acids in rat feces using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established and applied to analyze the fecal BAs in rats treated with VEK. The screened BA was then administered to VEK-treated MAE rats. The water-expelling effect was evaluated using histopathological analysis, biochemical examination, inflammatory factors in ascites, urine volume, ascites amount, and intestinal aquaporin expression. The microbial composition was determined using 16S rRNA sequencing, and the contents of bile acids were finally measured.Results: VEK decreased the content of fecal deoxycholic acid (DCA), lithocholic acid (LCA), and taurocholic acid (TCA) while increasing the content of ursodeoxycholic acid (UDCA). VEK alleviated liver, stomach, and intestinal injuries; oxidative damage; and inflammation, which were further ameliorated with UDCA intervention. VEK alleviated MAE by increasing the fecal water content, urine volume, and AQP3 protein expression and decreasing the urine levels of Na+, K+, and Cl−. This was retained with the intervention of UDCA. UDCA and VEK regulated the BA metabolism disorder to a certain extent. Analysis of gut microbiota showed that VEK increased the abundance of Lactobacillus and decreased that of Prevotella_9 in MAE rats. The combined administration of UDCA and VEK showed a better modulation of the microbiota structure than that of VEK alone, and the effect of this administration reached closer to the reference state.Conclusion: The water-expelling effect of VEK did not directly depend on the BA-mediated gut microbiota. However, VEK and BAs had a synergistic effect on malignant ascites effusion through the regulation of the gut microbiota. These results provided a scientific basis for the reasonable usage of VEK and the novel combination treatment strategy of VEK and UDCA.

Evodiamine (EVO) is a quinazoline carboline alkaloid isolated from the fruits of the traditional Chinese herb Evodiae fructus. In the present study, we synthesized thirty EVO derivatives (9–38) with various benzenesulfonyl groups by sulfonylation of the amino group of 3-NH-EVO and thirty benzenesulfonyl chloride substituents. The results of the MTT assay showed that most of the compounds had good antitumor activity on H460, PC9, PC9/GR, H1299 and SW620 cancer cells as well as on normal LO2 cells. Among them, compounds 9, 18 and 28 were more potent than other compounds on H460 cell lines with an IC50 value of 9.1 M, 10.5 M and 9.5 M, respectively, even more potent than the positive PGMI-004A with one IC50 of 31.1 M. The enzymatic activity of representative compounds was further evaluated against phosphoglycerate mutase 1 (PGAM1). The results showed that compound 11 with an IC50 of 0.062 μM and compound 34 with an IC50 of 0.059 μM were similar to the positive drug’s IC50 of 0.052 μM. These results indicated that these compounds could be developed into potential PGAM1 inhibitors. In addition, compounds 9, 18, and 28 could induce apoptosis, block the cell cycle at the G2/M stage, lead to bursting of reactive oxygen species, and induce mitochondrial dysfunction. Overall, the present work showed that the benzenesulfonyl chloride-substituted evodiamine derivatives have good antitumor activity against tumor cells and show promise as anticancer agents.

Abstract To investigate the outcomes of the modified radial tongue-shaped flap following stepwise surgery release for treating Benson type I camptodactyly of the 5th digit. A retrospective analysis involving patients with Benson type I camptodactyly of the 5th digit was performed. A total of 8 patients with 12 affected digits were included. Extent of surgical release depended on the degree of soft tissue contracture. Skin release, subcutaneous fascial release, and flexor digitorum superficialis tenotomy were performed in all 12 digits, sliding volar plate release in 2 digits, and intrinsic tendon transfer in 1 digit. The mean total passive motion of proximal interphalangeal joint significantly increased from 32.5° ± 16° to 86.3° ± 20.4°, while mean total active motion significantly increased from 22° ± 10.5° to 73.8° ± 27.5° (P

Abstract Hypertension is a global public health problem which affects the physical and mental health of individuals. The management of hypertension is a long‐term process that requires the cooperation of both doctors and patients, and the blood pressure variability is closely related to the clinical prognosis. In recent years, the development of telemedicine has promoted better blood pressure monitoring and management for patients, as well as better medical intervention and health education for patients by medical staff. This article provides a review of remote blood pressure monitoring and management.

Mutant isocitrate dehydrogenase 1 (mIDH1) is a common driving factor in acute myeloid leukemia (AML), with the R132 mutation accounting for a high proportion. The U.S. Food and Drug Administration (FDA) approved Ivosidenib, a molecular entity that targets IDH1 with R132 mutations, as a promising therapeutic option for AML with mIDH1 in 2018. It was of concern that the occurrence of disease resistance or recurrence, attributed to the IDH1 R132C/S280F second site mutation, was observed in certain patients treated with Ivosidenib within the same year. Furthermore, it should be noted that most mIDH1 inhibitors demonstrated limited efficacy against mutations at this specific site. Therefore, there is an urgent need to investigate novel inhibitors targeting mIDH1 for combating resistance caused by IDH1 R132C/S280F mutations in AML. This study aimed to identify novel mIDH1 R132C/S280F inhibitors through an integrated strategy of combining virtual screening and dynamics simulations. First, 2000 hits were obtained through structure-based virtual screening of the COCONUT database, and hits with better scores than −10.67 kcal/mol were obtained through molecular docking. A total of 12 potential small molecule inhibitors were identified through pharmacophore modeling screening and Prime MM-GBSA. Dynamics simulations were used to study the binding modes between the positive drug and the first three hits and IDH1 carrying the R132C/S280F mutation. RMSD showed that the four dynamics simulation systems remained stable, and RMSF and Rg showed that the screened molecules have similar local flexibility and tightness to the positive drug. Finally, the lowest energy conformation, hydrogen bond analysis, and free energy decomposition results indicate that in the entire system the key residues LEU120, TRP124, TRP267, and VAL281 mainly contribute van der Waals forces to the interaction, while the key residues VAL276 and CYS379 mainly contribute electrostatic forces.

Due to the advantages such as low multi-solution, high signal-to-noise ratio, low environmental impact, high efficiency and low cost, microbial prospection for oil and gas has been accepted for petroleum exploreration. With the rapid development of high-throughput sequencing, molecular biology and bioinformatics, describing the changes of specific oil and gas indicator micro-organisms from the perspective of microbial community as a whole has become an valuable progress of microbial exploration method for the future. In this paper, soil sampling, DNA extraction and analysis, discriminant model development and favorable area prediction are introduced, and soil DNA extraction as well as oil/gas indicator micro-organism detection are emphasized. With the study of industrial-grade DNA extraction technology, Griffth method has been considered as the best effect for the extraction and purification of soil microbial DNA. For projects with a large sample number, high-throughput pipetting workstations and commercial multi-well plate DNA extraction kits can greatly improve working efficiency. Integrated stable isotope probes and the molecular detection of high-throughput sequencing showed that the main hydrocarbon indicator microorganism strains typically imply the expected distribution. High frequency oil indicator bacteria (AMNR) are Arthrobacter, Mycobacterium, Nocardia, and Rhodospirillum, while high frequency gas indicator bacteria include Methylococcus, Methylobacterium, and Methylocystis. The preliminary application in the Hangjinqi area shows that the microbial molecular exploration technology can significantly improve the oil and gas identification accuracy in loess tableland regions, and has a good effect on the evaluation of oil and gas bearing property, which provides a reference for the selection of favorable tight gas regions in the northern part of Ordos Basin.

BackgroundThe impact of using invasive coronary angiography (ICA) or coronary computed tomography angiography (CCTA) as an initial examination on the incidence of major adverse cardiovascular events (MACEs) in patients with stable coronary artery disease and the occurrence of major operation-related complications is uncertain.ObjectiveThis study aimed to explore the effects of ICA vs. CCTA on MACEs, all-cause death, and major operation-related complications.MethodsA systematic search of electronic databases (PubMed and Embase) was conducted for randomized controlled trials and observational studies comparing MACEs between ICA and CCTA from January 2012 to May 2022. The primary outcome measure was analyzed using a random-effects model as a pooled odds ratio (OR). The main observations were MACEs, all-cause death, and major operation-related complications.ResultsA total of six studies, comprising 26,548 patients, met the inclusion criteria (ICA n = 8,472; CCTA n = 18,076). There were statistically significant differences between ICA and CCTA for MACE [OR 1.37; 95% confidence interval (CI), 1.06–1.77; p = 0.02], all-cause death (OR 1.56; 95% CI, 1.38–1.78; p

Abstract Background Functional exercises is very essential to the recovery of patients with fracture. We aimed to evaluate the compliance of functional exercises in school-age children with limb fracture, to provide evidence to the clinical management and nursing care of children with limb fracture. Methods School-age children with limb fractures treated in our hospital from January 1, 2020 to June 30, 2021 were selected. The characteristics and postoperative functional exercise compliance of included children were analyzed. Pearson correlation and Logistic regression analysis were conducted to analyze the influencing factors of compliance to functional exercises. Results A total of 328 children with limb fracture were included, the incidence of compliance to functional exercise was only 35.98%. Pearson correlation analysis showed that age(r = 0.707), only child of family(r = 0.537), guardians(r = 0.642) and type of temperament(r = 0.635) were correlated with compliance to functional exercises in school-age children with limb fractures (all p

Isocitrate dehydrogenase (IDH) is the key metabolic enzyme that catalyzes the conversion of isocitrate to α-ketoglutarate (α-KG). Two main types of IDH1 and IDH2 are present in humans. In recent years, mutations in IDH have been observed in several tumors, including glioma, acute myeloid leukemia, and chondrosarcoma. Among them, the frequency of IDH1 mutations is higher than IDH2. IDH1 mutations have been shown to increase the conversion of α-KG to 2-hydroxyglutarate (2-HG). IDH1 mutation-mediated accumulation of 2-HG leads to epigenetic dysregulation, altering gene expression, and impairing cell differentiation. A rapidly emerging therapeutic approach is through the development of small molecule inhibitors targeting mutant IDH1 (mIDH1), as evidenced by the recently approved of the first selective IDH1 mutant inhibitor AG-120 (ivosidenib) for the treatment of IDH1-mutated AML. This review will focus on mIDH1 as a therapeutic target and provide an update on IDH1 mutant inhibitors in development and clinical trials.

Microbial prospecting for oil and gas (MPOG) is a surface exploration technology derived from the principle of light hydrocarbon micro-seepage from oil and gas reservoirs. The light hydrocarbons (C1-C5) in oil and gas reservoirs permeate the overlying sedimentary layer in the way of micro-seepage, which induces the growth of microorganisms specializing in the consumption of light hydrocarbons in near-surface soil. As a result, the microbial concentration and community structure in oil and gas areas will be different from that without underlying oil and gas reservoirs. By analyzing the abnormal characteristics of microbial concentration and community structure, the oil and gas enrichment areas and oil and gas reservoirs are predicted. In recent years, the research team has established sample acquisition and pretreatment techniques for different geomorphology and surface types, and combined with traditional culturing and molecular biology methods, the precise diagnosis of oil and gas from the perspective of both hydrocarbon indication microorganism quantity and community structure is realized. The artificial simulation results lasting three years show that there are obvious differences and responsive relationships between the microorganisms and community structure under the acclimation of different hydrocarbon components. The strains found are consistent with the actual oil and gas reservoir, providing a theory basis for microbial exploration. In addition, the correlation among environmental conditions, hydrocarbon geochemistry and hydrocarbon microbial group distribution was studied using different oil and gas reservoir types and different geographical conditions. The rule of microbial community in situ of oil and gas reservoir samples was analyzed, and a database of oil and gas indicators in typical oil and gas basins in China was preliminarily constructed. The results showed that the surface microbial anomaly was closely related to the location of oil and gas reservoirs, and can reflectthe characteristics of oil and gas reservoirs of different types. Combined with petroleum geology and geophysical data, the microbial exploration technology can effectively predict the favorable enrichment areas of oil and gas. This paper also presents nine development trends of MPOG.

Intracerebral hemorrhage (ICH) is the most disabling form of stroke, but effective treatment protocols for ICH are still limited. The minimally invasive surgery (MIS) is a potential and effective treatment for ICH in recent years. However, it is associated with a risk of rebleeding. This review aims to discuss some key facts about rebleeding, such as thrombolytic agents, therapeutic time window, and first aspiration volume.

Star identification plays a key role in spacecraft attitude measurement. Currently, most star identification algorithms tend to perform well only in a scene without noise and are highly sensitive to noise. To solve this problem, this paper proposes a star identification algorithm based on the maximum spanning tree (MST) index and multi-order continuous cycle angle (CCA) intended for the lost-in-space mode. In addition, a neighboring star selection method named dynamic eight-quadrant (DEQ) is developed. First, the DEQ method is used to select high-confidence neighboring stars for the main star. Then, the star image is regarded as a graph, and the Prim algorithm is employed to construct the MST pattern for each guide star, which is then combined with the K vector index to perform the main star candidate search. Finally, the Jackard similarity voting for the multi-order CCA of the main star is used to identify the main star, and the global neighboring star identification is conducted by the multi-order CCA of neighboring stars. The simulated and real star images test results show that compared with five mainstream algorithms, when the position noise is 1 pixel, the number of false stars is five, the magnitude noise is 0.5, and the identification accuracy of the proposed algorithm is higher than 98.5%. Therefore, the proposed algorithm has excellent anti-noise ability in comparison to other algorithms.

Objectives: Early hematoma expansion in intracerebral hemorrhage (ICH) patients is strongly associated with poor outcome and potentially preventable if high-risk patients are timely identified. We aimed to investigate whether a novel sign detected by noncontrast computed tomography (NCCT) named absolute hypodensity sign (AHS) was an appropriate candidate for hematoma expansion prediction. Materials and Methods: Spontaneous ICH patients all underwent baseline NCCT scan within 6 h after ICH onset and the follow-up NCCT scan within 24 h after initial CT scan. AHS was defined as a hypoattenuating area with a distinct margin within the hematoma, the minimal density of which should be ≤30 Hounsfeld units. We used univariate and multivariate logistic regression analyses for determining the association between hematoma expansion and the presence of AHS. We also compared the diagnostic efficacy with blend sign and black hole sign. Results: A total of 348 ICH patients were included, 87 of which were found hematoma expansion. AHS was positive in 76 patients (21.8%) (κ = 0.88 for interrater reliability) and 63.2% of the patients with hematoma expansion were observed AHS. The multivariate logistic regression analysis demonstrated AHS was an independent predictor for hematoma expansion (odds ratio: 33.454, 95% confidence interval: 13.628–82.126, P

In recent years, microbial analysis has become a new detection technology in oil and gas surface exploration. The microbial diversity above a shale gas field was studied in order to further understand microbial information. High-throughput sequencing technology was used to study the abundance and diversity of hydrocarbon species in a shale gas field in the Dingshan area of the southeastern Sichuan Basin. Three main microorganisms were identified, including Methylophilales, Methylocystis, and Methylococcus, which are worthy of further biochemical research and can be used as potential oil and gas indicating bacteria. The developmental abundance of three kinds of microorganisms has a good matching relationship with the distribution of the fugitive area in Dingshan. The high-throughput analytical technology can be applied well in the study of oil and gas microorganisms in Dingshan area, and the distribution characteristics of microorganisms in bedrock samples were obtained. Furthermore, a preliminary analysis of the differences between oil and gas microbes in Dingshan and Jiaoshiba areas was made, indicating that the identified potential oil and gas indicating bacteria deserve further study.

Context As a toxic traditional Chinese medicine for edoema, Euphorbia kansui S.L. Liou ex S.B. Ho (Euphorbiaceae) (EK) stir-fried with vinegar for detoxification was associated with alterations of gut microbiota. However, the evidence of correlation between short-chain fatty acids (SCFAs) and toxicity of EK has not been confirmed. Objective In order to study the biological basis of detoxification of EK stir-fried with vinegar (VEK), a rapid, sensitive and validated GC-MS method was developed to determine SCFAs in normal rat faeces after given EK and VEK. Materials and methods Sprague Dawley rats were orally administered 0.5% CMC-Na (control group), EK (EK-treated group) and VEK powder (VEK-treated group) at 680 mg/kg for six consecutive days (eight rats each group). Fresh faeces samples were promptly collected, derivatized and then analyzed by GC-MS. Results The ranges of LOD and LOQ were within 0.13–1.79 and 0.45–5.95 μg/mL, respectively. The RSD values of intra-day and inter-day precisions were less than 15%. Four SCFAs were generally stable under four storage conditions. The extraction recoveries were ranged from 53.5% to 97.3% with RSD values lower than 15%. The concentrations of four SCFAs in EK and VEK were decreased significantly compared with those not administered (EK-treated, p

Background: Minimally invasive surgery for intracerebral hemorrhage (ICH) has been evaluated in clinical trials. Although meta-analyses on this topic have been performed in the past, recent trials have added important information to the results of the comparison. However, little work has been done to compare the effect of MIS and conventional treatment on patient prognosis, especially mortality.Methods: PubMed, EMBASE, Web of Science, Ovid, China National Knowledge Infrastructure, and ClinicalTrials.gov were searched on May 1, 2021, for randomized controlled trials of MIS for spontaneous ICH. The primary outcome was defined as death at follow-up, while the secondary outcome was defined as death in different comparisons between MIS and craniotomy (CT) or medication (Me).Results: The initial search yielded 12 high-quality randomized controlled trials involving 2,100 patients. We analyzed the odds ratios (ORs) for MIS compared with conventional treatment, including Me and conventional CT. The OR and confidence intervals (CIs) of the primary and secondary outcomes were 0.62 (0.45–0.85) for MIS vs. conventional treatment. We also conducted subgroup analyses and found that the ORs and CIs for MIS compared with that of conventional treatment in the short-term follow-up were 0.58 (0.42–0.80), and, in the long-term follow-up, was 0.67 (0.46–0.98); and found that ORs were 0.68 (0.48–0.98) for MIS vs. CT and 0.57 (0.41–0.79) for MIS vs. Me.Conclusions: This meta-analysis demonstrates that certain patients with ICH benefit in short- and long-term follow-up from MIS over other treatments, including open surgery and conventional Me.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/.

Background: Different from diabetic hyperglycemia, stress-induced hyperglycemia (SIH) can better reflect elevated blood glucose owing to intracerebral hemorrhage (ICH). However, studies about the outcome of ICH patients with SIH are still very limited. Aims: This study aimed to investigate whether SIH measured by stress-induced hyperglycemia ratio (SHR) was associated with hematoma expansion and poor outcomes in patients with ICH. Methods: A consecutive series of patients with spontaneous ICH from two clinical centers admitted within 24 h after symptom onset were enrolled for prospective analysis. SHR was defined as admission fasting blood glucose divided by estimated average glucose [1.59 × Hemoglobin A1c (%) − 2.59]. This study investigated the association between SHR and hematoma expansion, and short-term and long-term poor outcomes using univariate and multivariate logistic regression analyses. Results: A total of 313 ICH patients were enrolled in the study. SHR was markedly higher in patients with hematoma expansion and poor outcomes ( p

In order to improve the effect of rural garden landscape design, this paper combines virtual simulation technology to design rural garden landscape and evaluates its design effect. Moreover, this paper proposes an optical modulation system for the application of virtual simulation in rural garden landscape design. In addition, before the target is modulated, this paper converts the two-dimensional image on the detector target surface into a one-dimensional stretched modulation image so that the beam emitted by each object point is stretched and flattened on the detector target surface. Finally, this paper explores the influence of lens spacing and field of view on the modulation image of the target surface and the characteristics of projected intensity attenuation after modulation and designs a modulation model that optimizes attenuation. The research results show that the garden landscape design based on virtual reality technology proposed in this paper has a good effect and is of great significance to the effect of rural garden landscape design.

Although episodic star formation (SF) has been suggested for nearby SF regions, a panoramic view of the recent episodic SF history in the solar neighborhood is still missing. By uniformly constraining the slope α of infrared spectral energy distributions (SEDs) of young stellar objects (YSOs) in the 13 largest Gould’s Belt (GB) protoclusters surveyed by the Spitzer Space Telescope, we have constructed a cluster-averaged histogram of α representing the YSO evolution lifetime as a function of the α value. Complementary to the traditional SED classification scheme ( 0 , i , f , ii , and iii ) that is based on different α values, a staging scheme (A, B, C, D, and E) of SED evolution is proposed on the basis of the α statistical features that can be better matched to the physical stages of disk dissipation and giant planet formation. This has also allowed us to unravel the fluctuations of SF rate (SFR) in the 3 Myr history of these GB protoclusters. Diverse evolutionary patterns such as single peaks, double peaks, and ongoing acceleration of SFR are revealed. The SFR fluctuations are between 20% and 60% (∼40% on average) and no dependence on the average SFR or the number of SFR episodes is found. However, spatially close protoclusters tend to have similar SFR fluctuation trends, indicating that the driving force of the fluctuations should be at size scales beyond the typical cluster sizes of several parsecs.

Abstract Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifests principally as a suite of cognitive impairments, particularly in the executive domain. Executive functioning requires the dynamic coordination of neural activity over large-scale networks. It remains unclear whether changes in resting-state brain functional network connectivity and regional homogeneities (ReHos) underly the mechanisms of executive dysfunction evident in CADASIL patients. Methods In this study, 22 CADASIL patients and 44 matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). Independent component analysis (ICA) was used to measure functional brain network connectivity, and ReHos were calculated to evaluate local brain activities. We used seed-based functional connectivity (FC) analyses to determine whether dysfunctional areas (as defined by ReHos) exhibited abnormal FC with other brain areas. Relationships among the mean intra-network connectivity z-scores of dysfunctional areas within functional networks, and cognitive scores were evaluated using Pearson correlation analyses. Results Compared to the controls, CADASIL patients exhibited decreased intra-network connectivity within the bilateral lingual gyrus (LG) and the right cuneus (CU) (thus within the visual network [VIN)], and within the right precuneus (Pcu), inferior frontal gyrus (IFG), and precentral gyrus (thus within the frontal network [FRN]). Compared to the controls, patients also exhibited significantly lower ReHos in the right precuneus and cuneus (Pcu/CU), visual association cortex, calcarine gyri, posterior cingulate, limbic lobe, and weaker FC between the right Pcu/CU and the bilateral parahippocampal gyrus (PHG), and between the right Pcu/CU and the right postcentral gyrus. Notably, the mean connectivity z-scores of the bilateral LG and the right CU within the VIN were positively associated with compromised attention, calculation and delayed recall as revealed by tests of the various cognitive domains explored by the Mini-Mental State Examination. Conclusions The decreases in intra-network connectivity within the VIN and FRN and reduced local brain activity in the posterior parietal area suggest that patients with CADASIL may exhibit dysfunctional visuomotor behaviors (a hallmark of executive function), and that all visual information processing, visuomotor planning, and movement execution may be affected.

Abstract Glomerular podocytes play a key role in proteinuric diseases. Accumulating evidence suggests that cGMP signaling has podocyte protective effects. The major source of cGMP generation in podocytes is natriuretic peptides. The natriuretic peptide clearance receptor (NPRC) binds and degrades natriuretic peptides. As a result, NPRC inhibits natriuretic peptide‐induced cGMP generation. To enhance cGMP generation in podocytes, we blocked natriuretic peptide clearance using the specific NPRC ligand ANP(4‐23). We then studied the effects of NPRC blockade in both cultured podocytes and in a mouse transgenic (TG) model of focal segmental glomerulosclerosis (FSGS) created in our laboratory. In this model, a single dose of the podocyte toxin puromycin aminonucleoside (PAN) causes robust albuminuria in TG mice, but only mild disease in non‐TG animals. We found that natriuretic peptides protected cultured podocytes from PAN‐induced apoptosis, and that ANP(4‐23) enhanced natriuretic peptide‐induced cGMP generation in vivo. PAN‐induced heavy proteinuria in vehicle‐treated TG mice, and this increase in albuminuria was reduced by treatment with ANP(4‐23). Treatment with ANP(4‐23) also reduced the number of mice with glomerular injury and enhanced urinary cGMP excretion, but these differences were not statistically significant. Systolic BP was similar in vehicle and ANP(4‐23)‐treated mice. These data suggest that: 1. Pharmacologic blockade of NPRC may be useful for treating glomerular diseases such as FSGS, and 2. Treatment outcomes might be improved by optimizing NPRC blockade to inhibit natriuretic peptide clearance more effectively.

PGAM1 is overexpressed in a wide range of cancers, thereby promoting cancer cell proliferation and tumor growth, so it is gradually becoming an attractive target. Recently, a series of inhibitors with various structures targeting PGAM1 have been reported, particularly anthraquinone derivatives. In present study, the structure–activity relationships and binding mode of a series of anthraquinone derivatives were probed using three-dimensional quantitative structure–activity relationships (3D-QSAR), molecular docking, and molecular dynamics (MD) simulations. Comparative molecular field analysis (CoMFA, r2 = 0.97, q2 = 0.81) and comparative molecular similarity indices analysis (CoMSIA, r2 = 0.96, q2 = 0.82) techniques were performed to produce 3D-QSAR models, which demonstrated satisfactory results, especially for the good predictive abilities. In addition, molecular dynamics (MD) simulations technology was employed to understand the key residues and the dominated interaction between PGAM1 and inhibitors. The decomposition of binding free energy indicated that the residues of F22, K100, V112, W115, and R116 play a vital role during the ligand binding process. The hydrogen bond analysis showed that R90, W115, and R116 form stable hydrogen bonds with PGAM1 inhibitors. Based on the above results, 7 anthraquinone compounds were designed and exhibited the expected predictive activity. The study explored the structure–activity relationships of anthraquinone compounds through 3D-QSAR and molecular dynamics simulations and provided theoretical guidance for the rational design of new anthraquinone derivatives as PGAM1 inhibitors.

Primary brainstem hemorrhage (PBSH) is the most fatal subtype of intracerebral hemorrhage and is invariably associated with poor prognosis. Several prognostic factors are involved, of which the two most predominant and consistent are the initial level of consciousness and hemorrhage size. Other predictors, such as age, hyperthermia, and hydrocephalus, are generally not dependable indicators for making prognoses. Scoring systems have now been developed that can predict mortality and functional outcomes in patients suffering from PBSH, which can thus guide treatment decision-making. A novel grading scale, entitled “the new primary pontine hemorrhage (PPH) score,” represents the latest approach in scoring systems. In this system, patients with a score of 2–3 points appear to benefit from surgical management, although this claim requires further verification. The four main surgical options for the treatment of PBSH are craniotomy, stereotactic hematoma puncture and drainage, endoscopic hematoma removal, and external ventricular drainage. Nevertheless, the management of PBSH still primarily involves conservative treatment methods and surgery is generally not recommended, according to current practice. However, the ongoing clinical trial, entitled Safety and Efficacy of Surgical Treatment in Severe Primary Pontine Hemorrhage Evacuation (STIPE), should provide additional evidence to support the surgical treatment of PBSH. Therefore, we advocate the update of epidemiological data and re-evaluation of PBSH treatment in a contemporary context.

Evodiamine (EVO) and rutaecarpine (RUT) are the main active compounds of the traditional Chinese medicinal herb Evodia rutaecarpa. Here, we fully optimized the molecular geometries of EVO and RUT at the B3LYP/6-311++G (d, p) level of density functional theory. The natural population analysis (NPA) charges, frontier molecular orbitals, molecular electrostatic potentials, and the chemical reactivity descriptors for EVO and RUT were also investigated. Furthermore, molecular docking, molecular dynamics simulations, and the analysis of the binding free energies of EVO and RUT were carried out against the anticancer target topoisomerase 1 (TOP1) to clarify their anticancer mechanisms. The docking results indicated that they could inhibit TOP1 by intercalating into the cleaved DNA-binding site to form a TOP1–DNA–ligand ternary complex, suggesting that they may be potential TOP1 inhibitors. Molecular dynamics (MD) simulations evaluated the binding stability of the TOP1–DNA–ligand ternary complex. The calculation of binding free energy showed that the binding ability of EVO with TOP1 was stronger than that of RUT. These results elucidated the structure–activity relationship and the antitumor mechanism of EVO and RUT at the molecular level. It is suggested that EVO and RUT may be potential compounds for the development of new anticancer drugs.

Abstract Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) mainly manifests with cognitive impairment. Cognitive deficits in patients with CADASIL are correlated with structural brain changes such as lacunar lesion burden, normalized brain volume, and anterior thalamic radiation lesions, but changes in resting-state functional brain activity in patients with CADASIL have not been reported. Methods This study used resting-state functional magnetic resonance imaging (fMRI) to measure the amplitude of low-frequency fluctuation (ALFF) in 22 patients with CADASIL and 44 healthy matched controls. A seed-based functional connectivity (FC) analysis was used to investigate whether the dysfunctional areas identified by ALFF analysis exhibited abnormal FC with other brain areas. Pearson’s correlation analysis was used to detect correlations between the ALFF z-score of abnormal brain areas and clinical scores in patients with CADASIL. Results Patients with CADASIL exhibited significantly lower ALFF values in the right precuneus and cuneus (Pcu/CU) and higher ALFF values in the bilateral superior frontal gyrus (SFG) and left cerebellar anterior and posterior lobes compared with controls. Patients with CADASIL showed weaker FC between the areas with abnormal ALFF (using peaks in the left and right SFG and the right Pcu/CU) and other brain areas. Importantly, the ALFF z-scores for the left and right SFG were negatively associated with cognitive performance, including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment scores (MoCA), respectively, whereas those of the right Pcu/CU were positively correlated with the MMSE score. Conclusions This preliminary study provides evidence for changes in ALFF of the right Pcu/CU, bilateral SFG and left cerebellar anterior and posterior lobes, and associations between ALFF values for abnormal brain areas and cognitive performance in patients with CADASIL. Therefore, spontaneous brain activity may be a novel imaging biomarker of cognitive impairment in this population.

IDH1 mutations occur in about 20–30% of gliomas and are a promising target for the treatment of cancer. In the present study, the performance of aIDH1R132H was verified via glide-docking-based virtual screening. On the basis of the two crystal structures (5TQH and 6B0Z) with the best discriminating ability to identify IDH1R132H inhibitors from a decoy set, a docking-based virtual screening strategy was employed for identifying new IDH1R132H inhibitors. In the end, 57 structurally diverse compounds were reserved and evaluated through experimental tests, and 10 of them showed substantial activity in targeting IDH1R132H (IC50 < 50 μM). Molecular docking technology showed that L806-0255, V015-1671, and AQ-714/41674992 could bind to the binding pocket composed of hydrophobic residues. These findings indicate that L806-0255, V015-1671, and AQ-714/41674992 have the potential as lead compounds for the treatment of IDH1-mutated gliomas through further optimization.

In traditional Chinese Medicine (TCM), the licorice-yuanhua herbal pair is one of the most representative incompatible herbal pairs recorded in the “eighteen incompatible herbal pairs” theory. Previous studies of our research group have demonstrated several gut-related side-effects induced by the licorice-yuanhua herbal pair. In this study, we investigated whether and why this incompatible herbal pair could induce gut tissue damage. After licorice-yuanhua treatment, the duodenum, ileum, and colon and serum biomarkers of mice were examined by pathological staining, Western blot, and ELISA assays. The IEC-6 cells and LS174T cells were treated with licorice saponins, yuanhua flavonoids, and di-terpenes; iTRAQ-labeled proteomic technology was then used to explore their synergistic effects on mucosa cells, followed by verification of ZO-1 and MUC-2 protein expressions. The results showed that the licorice-yuanhua herbal pair induced ileum tissue injuries, including epithelial integrity loss, inflammation, and edema. These injuries were verified to be related to epithelial and mucous barrier weakening, such as downregulated ileum ZO-1 and MUC-2 protein expressions. Proteomic analysis also suggested that glycyrrhizic acid and genkwanin synergistically influence tight junction pathways in LS174T cells. Furthermore, licorice saponins, yuanhua flavonoids, and di-terpenes dose/structure-dependently downregulate ZO-1 and MUC-2 protein expressions in mucosa cells. Our study provides different insights into the incompatibility mechanisms and material basis of the licorice-yuanhua herbal pair, especially that besides toxic di-terpenes, licorice saponins and yuanhua flavonoids, which are commonly known to be non-toxic compounds, can also take part in the gut damage induced by the licorice-yuanhua herbal pair.

Abstract As recorded in Traditional Chinese Medicine (TCM) theory, Gancao (Glycyrrhizae Radix et Rhizoma) could weaken the pharmacological effect or increase the toxicity of Yuanhua (Genkwa Flos). However, the theory has been suspected due to lack of evidence. Here, we investigate whether Gancao could weaken Yuanhua’s diuretic effect, if so, which chemicals and which targets may be involved. Results showed that Yuanhua exerted diuretic effect through down-regulating renal AQP 2, without electrolyte disturbances such as K+ loss which has been observed as side-effect of most diuretics. Gancao had no diuretic effect, but could impair Yuanhua’s diuretic effect through up-regulating renal AQP 2. Glycyrrhetinic acid (GRA) in Gancao could up-regulate AQP 2 and counteract the AQP 2 regulation effect of Yuanhuacine (YHC) and Ginkwanin (GKW) in Yuanhua. Network pharmacology method suggested that YHC, GKW and GRA could bind to MEK1/FGFR1 protein and influence ERK-MAPK pathway, which was verified by Western blotting. This study supports TCM theory and reminds that more attention should be paid to the safety and efficacy problems induced by improper combination between herbs. Moreover, we suggested that promising diuretics with less side effects can be developed from Chinese Medicines such as Yuanhua.

Peiminine is a compound isolated from Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae family), which has demonstrated antitumor activities. But its precise molecular mechanism underlying antitumor activity remain elusive. In this study, peiminine-induced apoptosis towards human hepatocellular carcinoma and its molecular mechanism were investigated. MTT assay was employed to assess anticancer effects of peiminine upon Hela, HepG2, SW480 and MCF-7 cell lines. Nuclear staining and flow cytometry were carried out to detect apoptosis induced by peiminine. Mitochondrial membrane potential evaluation and Western blot analysis were performed to investigate the mechanism of peiminine-induced apoptosis. The results showed peiminine reduced the viability of HepG2 cells in a time- and dose-dependent manner and had an IC50 of 4.58 μg/mL at 24h. Peiminine significantly increased the percentage of apoptotic cells and the mitochondrial membrane potential dose-dependently in HepG2 cells. The results of Western blotting indicated the expressions of Bcl-2, procaspase-3, procaspase-8, procaspase-9, and PARP decreased in HepG2 cells treated with peiminine, while the expressions of Bax, caspase-3, caspase-8, caspase-9, and cleaved PARP1 increased. The result suggests that peiminine can induce apoptosis in human hepatocellular carcinoma HepG2 cells through both extrinsic and intrinsic apoptotic pathways.

Chinese jujube (Ziziphus jujuba), a medicinal and edible plant, is widely consumed in Asian countries owing to the remarkable health activities of its fruits. To facilitate selection of the suitable processing method for jujube fruits, in this study their contents of triterpenic acids, nucleosides, nucleobases and saccharides after drying and steaming treatment were determined using ultra-high performance liquid chromatography and high performance liquid chromatography coupled with evaporative light scattering detector methods. The results showed that except for sucrose, the content levels of most analytes were increasing in the jujube fruits during drying treatment at 45 °C. The levels of cyclic nucleotides such as adenosine 3′,5′-cyclic monophosphate and guanosine 3′,5′-cyclic monophosphate, were significantly decreased after the fruits were steamed. Therefore, owing to the bioactivities of these components for human health, the dried fruits would be the better choice as medicinal material or functional food, and dried jujube fruit should not be further steamed.

Kansenone is a triterpene from the root of the traditional Chinese medicine, Euphorbia kansui. However, kansenone exerts serious toxicity, but the exact mechanism was not clear. In this work, the effects of kansenone on cell proliferation, cell cycle, cell damage, and cell apoptosis were investigated. The suppression of cell proliferation was assessed via the colorimetric MTT assay, and cell morphology was visualized via inverted microscopy after IEC-6 cells were incubated with different concentrations of kansenone. Reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) content were detected for evaluating cell damage. RNase/propidium iodide (PI) labeling for evaluation of cell cycle distribution was performed by flow cytometry analysis. Annexin V-fluorescein isothiocyanate (FITC)/PI and Hoechst 33342/Annexin V-FITC/PI staining assay for cell apoptosis detection were performed using confocal laser scanning microscopy and high content screening. Moreover, apoptosis induction was further confirmed by transmission electron microscope (TEM) and JC-1 mitochondrial membrane potential, western blot and RT-PCR analysis. The results demonstrated that kansenone exerted high cytotoxicity, induced cell arrest at G0/G1 phase, and caused mitochondria damage. In addition, kansenone could up-regulate the apoptotic proteins Bax, AIF, Apaf-1, cytochrome c, caspase-3, caspase-9, caspase-8, FasR, FasL, NF-κB, and TNFR1 mRNA expression levels, and down-regulate the anti-apoptotic Bcl-2 family proteins, revealing that kansenone induces apoptosis through both the death receptor and mitochondrial pathways.

The Ziziphus species are considered to be the medicine and food dual purposes plants. Among them, the seed of Ziziphus jujuba var. spinosa (ZS) has traditionally been used as an ethnomedicine in Asian countries for thousands years. Owing to the significant benefits for human health, the demand for ZS increased year by year, and the wild resources have become increasingly scarce, which resulted in a shortage of market supply for ZS and product adulteration by substituting ZS with the seeds of Z. mauritiana Lam. (ZM). However, whether the bioactivity of ZM is similar to ZS has not been fully confirmed till now. Thus, to provide potential information for evaluating the similarity of the health promoting activities between these two Ziziphus seeds, their chemical profiles, including triterpenoids, flavonoids, nucleosides, free amino acids and fatty acids were compared using high-performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD), ultra-high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-TQ MS), and gas chromatography coupled with mass spectrometry (GC-MS) methods. Furthermore, a more holistic investigation was performed with multivariate principle component analysis and orthogonal projections to latent structures-discriminant analysis analyses to explore the relative variability between the seeds of two species. The results showed that a significant difference exists between ZS and ZM, and ZS was more rich in saponins, polyunsaturated fatty acids and some amino acids, whereas ZM was particularly rich in saturated fatty acids and flavonoids. The above results suggested the bioactivities of ZM for human health may not be similar to ZS owing to their difference in chemical profiles. These results would also be helpful for distinguishing the ZM from ZS with the chemical markers obtained from the study, and set a scientific foundation for establishing the quality control method of ZS.

Caffeic acid phenethyl ester (CAPE), as one of the main active ingredients of the natural product propolis, shows the unique biological activities such as anti-tumor, anti-oxidation, anti-inflammatory, immune regulation, and so on. These have attracted the attention of many researchers to explore the compound with potent biological activities. This review aims to summarize its bioactivities, synthetic methods and derivatives, which will be helpful for further study and development of CAPE and its derivatives.

Siji-kangbingdu mixture is an anti-inflammatory, anti-bacterial, and anti-viral herbal mixture which is frequently used by doctors to treat upper respiratory infections. It’s important to establish an efficient and economical quality-control method to ensure the quality consistency and efficacy stability of Siji-kangbingdu mixture. In this study, an integrated multi-evaluation method was established, sequentially involving UPLC-TripleTOF-MS analysis, UPLC fingerprint analysis, and the quantitative analysis of multi-components using the single-marker (QAMS) method. With one chromatographic condition, a total of 71 compounds were identified by MS and MS/MS information, with a mass error of less than 5 ppm; 49 peaks detected in 254 nm were selected to establish the fingerprint similarity model, and 7 chemical compounds were simultaneously determined, namely, chlorogenic acid, liquiritin, rutin, isochlorogenic acid A, forsythin, forsythoside A, and glycyrrhizic acid, with forsythoside A as the reference standard. There was no significant difference in the content of the seven compounds between the QAMS method and the external standard method (ESM). The established multi-evaluation method will largely promote the quality control and standardization process of Siji-kangbingdu mixture. It also provides a reference workflow for the overall evaluation of TCM patent medicines, from chemical profiling to fingerprint and quantitative analysis.

Euphorbia kansui stir-fried with vinegar (V-kansui) has promising biological activities toward treating malignant ascites with reduced toxicity compared to crude kansui. But the mechanism concerning promoting the excretion of ascites has not been systematically studied. The purpose of this paper was to investigate the possible mechanism of V-kansui in treating malignant ascites, including metabolic pathways and molecular mechanism using an integrated serum and urine metabolomics coupled with network pharmacology. Serum and urine samples of rats were collected and analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A comparison with crude kansui was also made to demonstrate the feasibility of processing. Principle component analysis (PCA) and orthogonal partial least square discriminate analysis (OPLS-DA) were conducted to discriminate the groups, search important variables and reveal the possible pathways. A compound-target-metabolite network was finally constructed to identify the crucial targets to further understand the molecular mechanism. Sixteen significant metabolites contributing to the discrimination of model and control groups were tentatively screened out. They were mainly involved in the arachidonic acid metabolism, steroid hormone biosynthesis and primary bile acid to possibly reduce inflammatory and modulate the renin-angiotensin-aldosterone system to achieve treating malignant ascites. A bio-network starting from the compounds and ending in the metabolites was constructed to elucidate the molecular mechanism. HSP90AA1, ANXA2, PRDX6, PCNA, SOD2 and ALB were identified as the potential key targets that were responsible for the treatment of malignant ascites by the parameter combining the average shortest path length and betweenness centrality. The correlated 17 compounds were considered as the potential active ingredients in V-kansui. In addition, the metabolomics showed that the effect of V-kansui was almost in accordance with crude kansui. These results systematically revealed the mechanism of V-kansui against malignant ascites for the first time using metabolomics coupled with network pharmacology. V-kansui could be a promising safe and therapeutic medicine for the excretion of ascites.

In the present study, the process of ultrasonic assisted enzymatic extraction (UAEE), followed by macroporous resin purification, was successfully developed to achieve maximal recovery of flavonoids and ginkgolides from Ginkgo biloba fallen leaves (GBFL). Three effective extracted factors, including UAE power, EtOH%, and the amount of cellulase were screened by Plackett–Burman design (PBD). The important variables were further optimized by rotatable central composite design (RCCD). After the combination of PBD and RCCD, the resulting optimal UAEE conditions were as follows: UAE power of 218 W; EtOH% of 68%; the amount of cellulase of 8.4 mg; UAE temperature of 40 °C; UAE time of 20 min; pH of 5.0; and, sample particle size of 40 mesh. Under the optimum conditions; the yields of flavonoids were 0.74 ± 0.05% (n = 3) and ginkgolides was 0.42 ± 0.06% (n = 3), which were close to the predicted values. Moreover, the further enriching flavonoids and ginkgolides from the obtained GBFL extracts using the above optimum UAEE condition was successfully achieved by macroporous resin DA-201. After column adsorption and desorption on DA-201; the percentage of total flavonoids was (25.36 ± 1.03)%; ginkgolides was (12.43 ± 0.85)% and alkylphenols was (0.003 ± 0.0005)% from the obtained dry extracts of GBFL which were complied with Chinese pharmacopoeias. Therefore, the present study provided a convenient and efficient method for extraction and purification of flavonoids and ginkgolides from waste GBFL.

Granulocyte-colony stimulating factor (G-CSF) has been shown to play a neuroprotective role in ischemic stroke by mobilizing bone marrow (BM)-derived endothelial progenitor cells (EPCs), promoting angiogenesis, and inhibiting apoptosis. Impairments in mobilization and function of the BM-derived EPCs have previously been reported in animal and human studies of diabetes where there is both reduction in the levels of the BM-derived EPCs and its ability to promote angiogenesis. This is hypothesized to account for the pathogenesis of diabetic vascular complications such as stroke. Here, we sought to investigate the effects of G-CSF on diabetes-associated cerebral vascular defect. We observed that pretreatment of the cultured human brain vascular endothelial cells (HBVECs) with G-CSF largely prevented cell death induced by the combination stimulus with high glucose, free fatty acids (FFA) and hypoxia by increasing cell viability, decreasing apoptosis and caspase-3 activity. Cell ultrastructure measured by transmission electron microscope (TEM) revealed that G-CSF treatment nicely reduced combination stimulus-induced cell apoptosis. The results from fluorescent probe Fluo-3/AM showed that G-CSF greatly suppressed the levels of intracellular calcium ions under combination stimulus. We also found that G-CSF enhanced the expression of cell cycle proteins such as human cell division cycle protein 14A (hCdc14A), cyclinB and cyclinE, inhibited p53 activity, and facilitated cell cycle progression following combination stimulus. In addition, activation of extracellular signal-regulated kinase1/2 (ERK1/2) and Akt, and deactivation of c-Jun N terminal kinase (JNK) and p38 were proved to be required for the pro-survival effects of G-CSF on HBVECs exposed to combination stimulus. Overall, G-CSF is capable of alleviating HBVECs injury triggered by the combination administration with high glucose, FFA and hypoxia involving the mitogen-activated protein kinases (MAPK) and Akt signaling cascades. G-CSF may represent a promising therapeutic agent for diabetic stroke.

For more than thirty years, scutellarin (Scu) has been used in China to clinically treat acute cerebral infarction and paralysis. Scutellarein (Scue), the major Scu metabolite in vivo, exhibits heightened neuroprotective effects when compared to Scu. To explore the neuroprotective role of these compounds, we performed ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-QTOF/MS) coupled with a pattern recognition approach to investigate metabolomic differences in a rat model of ischemia after treatment with each compound. We examined metabolites in urine, hippocampal tissue, and plasma, and we tentatively identified 23 endogenous metabolites whose levels differed significantly between sham-operated and model groups. Upon pathway analysis, we found an additional 11 metabolic pathways in urine, 14 metabolic pathways in the hippocampal tissue, and 3 metabolic pathways in plasma. These endogenous metabolites were mainly involved in sphingolipid metabolism, lysine biosynthesis, and alanine, aspartate, and glutamate metabolism. We found that metabolic changes after ischemic injury returned to near-normal levels after Scue intervention, unlike Scu treatment, further validating the heightened protective effects exerted by Scue compared to Scu. These results demonstrate that Scue is a potential drug for treatment of ischemic insult.

Thais clavigera, as function food, is distributed widely along the coasts of China. To compare and tap its potentially nutritional and functional values, hydrophilic interaction ultra-performance liquid chromatography coupled with triplequadrupole tandem mass spectrometry (HILIC-UPLC-TQ-MS/MS) was used for simultaneous identification and quantification of amino acids, nucleosides, and nucleobases in the extracts of T. clavigera from 19 sea areas in China, and a PCA was further performed for comparing their content variation in different distribution regions. The total contents of amino acids varied from 116.74 mg/g to 298.58 mg/g being higher than contents of nucleosides and nucleobases that varied from 2.65 mg/g and 20.49 mg/g. Among the habitats, Hainan province had content advantages on others. By PCA, samples collected from different regions were classified into three groups. For specific constituents, lysine accounted for large part of essential amino acids; glycine and taurine also play important roles in the delicate taste and health care function of it. Inosine takes up most of total contents of nucleosides and nucleobases. These results provided good data for establishing quality standard of T. clavigera related products and their further development and utilization.

Cerebrovascular diseases are conditions caused by problems with brain vasculature, which have a high morbidity and mortality. Aquaporin-4 (AQP4) is the most abundant water channel in the brain and crucial for the formation and resolution of brain edema. Considering brain edema is an important pathophysiological change after stoke, AQP4 is destined to have close relation with cerebrovascular diseases. However, this relation is not limited to brain edema due to other biological effects elicited by AQP4. Till now, multiple studies have investigated roles of AQP4 in cerebrovascular diseases. This review focuses on expression of AQP4 and the effects of AQP4 on brain edema and neural cells injuries in cerebrovascular diseases including cerebral ischemia, intracerebral hemorrhage and subarachnoid hemorrhage. In the current review, we pay more attention to the studies of recent years directly from cerebrovascular diseases animal models or patients, especially those using AQP4 gene knockout mice. This review also elucidates the potential of AQP4as an excellent therapeutic target.

Natural product lingenol, a purified diterpenoid compound derived from the root of Euphorbia kansui, exerts serious hepatotoxicity; however, the molecular mechanisms remain to be defined. In the present study, cell counting Kit-8 (CCK-8), inverted phase contrast microscope and flow cytometry were used to demonstrate that lingenol significantly inhibited L-O2 cells proliferation, and induced cell cycle arrest and apoptosis. Moreover, the results investigated that lingenol markedly disrupted mitochondrial functions by high content screening (HCS). In addition, the up-regulation of cytochrome c, AIF and Apaf-1 and activation of caspases were found in L-O2 cells detected by Western blotting and ELISA assay, which was required for lingenol activation of cytochrome c-mediated caspase cascades and AIF-mediated DNA damage. Mechanistic investigations revealed that lingenol significantly down-regulated the Bcl-2/Bax ratio and enhanced the reactive oxygen species (ROS) in L-O2 cells. These data collectively indicated that lingenol modulation of ROS and Bcl-2/Bax ratio led to cell cycle arrest and mitochondrial-mediated apoptosis in L-O2 cells in vitro. All of these results will be helpful to reveal the hepatotoxicity mechanism of Euphorbia kansui and to effectively guide safer and better clinical application of this herb.

To evaluate the nutritional and functional value of Sipunculus nudus, a rapid, simple and sensitive analytical method was developed using ultra-high performance liquid chromatography coupled with a triple quadrupole mass detection in multiple-reaction monitoring mode for the simultaneous quantitative determination of 25 free amino acids and 16 nucleosides and nucleobases in S. nudus within 20 min, which was confirmed to be reproducible and accurate. The limits of detection (LODs) and quantification (LOQs) were between 0.003–0.229 μg/mL and 0.008–0.763 μg/mL for the 41 analytes, respectively. The established method was applied to analyze 19 batches of S. nudus samples from four habitats with two different processing methods. The results showed that S. nudus contained a variety of free amino acids, nucleosides and nucleobases in sufficient quantity and reasonable proportion. They also demonstrated that the contents of these compounds in different parts of S. nudus were significantly discriminating, which were in the order: (highest) coelomic fluid > body wall > intestine (lowest). The method is simple and accurate, and could serve as a technical support for establishing quality control of S. nudus and other functional seafoods. Moreover, the research results also laid foundation for further exploitation and development of S. nudus.

Radix Salviae miltiorrhizae et Rhizoma, known as Danshen in China, is one of the most popular traditional Chinese medicines. Recently, there has been increasing scientific attention on Danshen for its remarkable bioactivities, such as promoting blood circulation, removing blood stasis, and clearing away heat. This review summarized the advances in chemical analysis of Danshen and its preparations since 2009. Representative established methods were reviewed, including spectroscopy, thin layer chromatography, gas chromatography, liquid chromatography (LC), liquid chromatography-mass spectrometry (LC-MS), capillary electrophoresis, electrochemistry, and bioanalysis. Especially the analysis of polysaccharides in Danshen was discussed for the first time. Some proposals were also put forward to benefit quality control of Danshen.