Fingolimod synergizes and reverses K. pneumoniae resistance to colistin.

Klebsiella pneumoniae (K. pneumoniae) infection and the rapid spread of multi-drug resistant (MDR) bacteria pose a serious threat to global healthcare. Polymyxin E (colistin), a group of cationic antimicrobial polypeptides, is currently one of the last resort treatment options against carbapenem-resistant Gram-negative pathogens. The effectiveness of colistin has been compromised due to its intensive use. This study found that fingolimod (FLD), a natural product derivative, exhibited a significant synergistic bactericidal effect on K. pneumoniae when combined with colistin, both in vitro and in vivo. The checkerboard method was employed to assess the in vitro synergistic effect of FLD with colistin. FLD enhanced the susceptibility of bacteria to colistin and lowered effectively minimum inhibitory concentrations (MIC) when compared to colistin MIC, and the fractional inhibitory concentrations (FIC) value was less than 0.3. The time-kill curve demonstrated that the combination treatment of FLD and colistin had significant bactericidal efficacy. The in vitro concurrent administration of colistin and FLD resulted in heightening membrane permeability, compromising cell integrity, diminishing membrane fluidity, and perturbing membrane homeostasis. They also induced alterations in membrane potential, levels of reactive oxygen species, and adenosine triphosphate synthesis, ultimately culminating in bacterial death. Moreover, the combination of FLD with colistin significantly influenced fatty acid metabolism. In the mouse infection model, the survival rate of mice injected with K. pneumoniae was significantly improved to 67% and pathological damage was significantly relieved with combination treatment of FLD and colistin when compared with colistin treatment. This study highlights the potential of FLD in combining with colistin for treating infections caused by MDR isolates of K. pneumoniae.

Observation of Momentum Space Josephson Effects in Weakly Coupled Bose-Einstein Condensates.

The momentum space Josephson effect describes the supercurrent flow between weakly coupled Bose-Einstein condensates (BECs) at two discrete momentum states. Here, we experimentally observe this exotic phenomenon using a BEC with Raman-induced spin-orbit coupling, where the tunneling between two local band minima is implemented by the momentum kick of an additional optical lattice. A sudden quench of the Raman detuning induces coherent spin-momentum oscillations of the BEC, which is analogous to the ac Josephson effect. We observe both plasma and regular Josephson oscillations in different parameter regimes. The experimental results agree well with the theoretical model and numerical simulation and showcase the important role of nonlinear interactions. We also show that the measurement of the Josephson plasma frequency gives the Bogoliubov zero quasimomentum gap, which determines the mass of the corresponding pseudo-Goldstone mode, a long-sought phenomenon in particle physics. The observation of momentum space Josephson physics offers an exciting platform for quantum simulation and sensing utilizing momentum states as a synthetic degree.

Two-photon imaging of excitatory and inhibitory neural response to infrared neural stimulation.

Significance: Pulsed infrared neural stimulation (INS, 1875 nm) is an emerging neurostimulation technology that delivers focal pulsed heat to activate functionally specific mesoscale networks and holds promise for clinical application. However, little is known about its effect on excitatory and inhibitory cell types in cerebral cortex. Aim: Estimates of summed population neuronal response time courses provide a potential basis for neural and hemodynamic signals described in other studies. Approach: Using two-photon calcium imaging in mouse somatosensory cortex, we have examined the effect of INS pulse train application on hSyn neurons and mDlx neurons tagged with GCaMP6s. Results: We find that, in anesthetized mice, each INS pulse train reliably induces robust response in hSyn neurons exhibiting positive going responses. Surprisingly, mDlx neurons exhibit negative going responses. Quantification using the index of correlation illustrates responses are reproducible, intensity-dependent, and focal. Also, a contralateral activation is observed when INS applied. Conclusions: In sum, the population of neurons stimulated by INS includes both hSyn and mDlx neurons; within a range of stimulation intensities, this leads to overall excitation in the stimulated population, leading to the previously observed activations at distant post-synaptic sites.

Cross-and-Diagonal Networks: An Indirect Self-Attention Mechanism for Image Classification.

In recent years, computer vision has witnessed remarkable advancements in image classification, specifically in the domains of fully convolutional neural networks (FCNs) and self-attention mechanisms. Nevertheless, both approaches exhibit certain limitations. FCNs tend to prioritize local information, potentially overlooking crucial global contexts, whereas self-attention mechanisms are computationally intensive despite their adaptability. In order to surmount these challenges, this paper proposes cross-and-diagonal networks (CDNet), innovative network architecture that adeptly captures global information in images while preserving local details in a more computationally efficient manner. CDNet achieves this by establishing long-range relationships between pixels within an image, enabling the indirect acquisition of contextual information. This inventive indirect self-attention mechanism significantly enhances the network's capacity. In CDNet, a new attention mechanism named "cross and diagonal attention" is proposed. This mechanism adopts an indirect approach by integrating two distinct components, cross attention and diagonal attention. By computing attention in different directions, specifically vertical and diagonal, CDNet effectively establishes remote dependencies among pixels, resulting in improved performance in image classification tasks. Experimental results highlight several advantages of CDNet. Firstly, it introduces an indirect self-attention mechanism that can be effortlessly integrated as a module into any convolutional neural network (CNN). Additionally, the computational cost of the self-attention mechanism has been effectively reduced, resulting in improved overall computational efficiency. Lastly, CDNet attains state-of-the-art performance on three benchmark datasets for similar types of image classification networks. In essence, CDNet addresses the constraints of conventional approaches and provides an efficient and effective solution for capturing global context in image classification tasks.

A combined transcriptomics and proteomics approach to reveal the mechanism of AEE relieving hyperlipidemia in ApoE-/- mice.

Hyperlipidemia caused by abnormal lipid metabolism has reached epidemic proportions. This phenomenon is also common in companion animals. Previous studies showed that AEE significantly improves abnormal blood lipids in hyperlipidemia rats and mice, but its mechanism is still not clear enough. In this study, the mechanism and potential key pathways of AEE on improving hyperlipidemia in mice were investigated through the transcriptome and proteome study of ApoE-/- mice liver and the verification study on high-fat HepG2 cells. The results showed that AEE significantly decreased the serum TC and LDL-C levels of hyperlipidemia ApoE-/- mice, and significantly increased the enzyme activity of CYP7A1. After AEE intervention, the results of mice liver transcriptome and proteome showed that differential genes and proteins were enriched in lipid metabolism-related pathways. The results of RT-qPCR showed that AEE significantly regulated the expression of genes related to lipid metabolism in mice liver tissue. AEE significantly upregulated the protein expression of CYP7A1 in hyperlipidemia ApoE-/- mice liver tissue. The results in vitro showed that AEE significantly decreased the levels of TC and TG, and improved lipid deposition in high-fat HepG2 cells. AEE significantly increased the expression of CYP7A1 protein in high-fat HepG2 cells. AEE regulates the expression of genes related to lipid metabolism in high-fat HepG2 cells, mainly by FXR-SHP-CYP7A1 and FGF19-TFEB-CYP7A1 pathways. To sum up, AEE can significantly improve the hyperlipidemia status of ApoE-/- mice and the lipid deposition of high-fat HepG2 cells, and its main pathway is probably the bile acid metabolism-related pathway centered on CYP7A1.

A minimal physical model for curvotaxis driven by curved protein complexes at the cell's leading edge.

Cells often migrate on curved surfaces inside the body, such as curved tissues, blood vessels, or highly curved protrusions of other cells. Recent in vitro experiments provide clear evidence that motile cells are affected by the curvature of the substrate on which they migrate, preferring certain curvatures to others, termed "curvotaxis." The origin and underlying mechanism that gives rise to this curvature sensitivity are not well understood. Here, we employ a "minimal cell" model which is composed of a vesicle that contains curved membrane protein complexes, that exert protrusive forces on the membrane (representing the pressure due to actin polymerization). This minimal-cell model gives rise to spontaneous emergence of a motile phenotype, driven by a lamellipodia-like leading edge. By systematically screening the behavior of this model on different types of curved substrates (sinusoidal, cylinder, and tube), we show that minimal ingredients and energy terms capture the experimental data. The model recovers the observed migration on the sinusoidal substrate, where cells move along the grooves (minima), while avoiding motion along the ridges. In addition, the model predicts the tendency of cells to migrate circumferentially on convex substrates and axially on concave ones. Both of these predictions are verified experimentally, on several cell types. Altogether, our results identify the minimization of membrane-substrate adhesion energy and binding energy between the membrane protein complexes as key players of curvotaxis in cell migration.

Fingolimod Inhibits Exopolysaccharide Production and Regulates Relevant Genes to Eliminate the Biofilm of K. pneumoniae.

Klebsiella pneumoniae (K. pneumoniae) exhibits the ability to form biofilms as a means of adapting to its adverse surroundings. K. pneumoniae in this biofilm state demonstrates remarkable resistance, evades immune system attacks, and poses challenges for complete eradication, thereby complicating clinical anti-infection efforts. Moreover, the precise mechanisms governing biofilm formation and disruption remain elusive. Recent studies have discovered that fingolimod (FLD) exhibits biofilm properties against Gram-positive bacteria. Therefore, the antibiofilm properties of FLD were evaluated against multidrug-resistant (MDR) K. pneumoniae in this study. The antibiofilm activity of FLD against K. pneumoniae was assessed utilizing the Alamar Blue assay along with confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and crystal violet (CV) staining. The results showed that FLD effectively reduced biofilm formation, exopolysaccharide (EPS), motility, and bacterial abundance within K. pneumoniae biofilms without impeding its growth and metabolic activity. Furthermore, the inhibitory impact of FLD on the production of autoinducer-2 (AI-2) signaling molecules was identified, thereby demonstrating its notable anti-quorum sensing (QS) properties. The results of qRT-PCR analysis demonstrated that FLD significantly decreased the expression of genes associated with the efflux pump gene (AcrB, kexD, ketM, kdeA, and kpnE), outer membrane (OM) porin proteins (OmpK35, OmpK36), the quorum-sensing (QS) system (luxS), lipopolysaccharide (LPS) production (wzm), and EPS production (pgaA). Simultaneously, FLD exhibited evident antibacterial synergism, leading to an increased survival rate of G. mellonella infected with MDR K. pneumoniae. These findings suggested that FLD has substantial antibiofilm properties and synergistic antibacterial potential for colistin in treating K. pneumoniae infections.

Clinical significance of nucleolar antinuclear antibodies associated with the nucleolar immunofluorescence pattern in autoimmune disease / 国际检验医学杂志

Objective To explore the clinical significance of nucleolar antinuclear antibodies(ANA)in re-lated diseases.Methods This study was a retrospective study.Clinical samples of 71780 patients who visited the hospital from January 2017 to May 2022 were collected.Indirect immunofluorescence was used to detect ANA in clinical samples.Statistical analysis was conducted on the positivity rate of nucleolar ANA in clinical patients,as well as the relevant clinical information and laboratory characteristics of patients with autoimmune diseases(AID)with nucleolar ANA positivity.Results Among 71780 patients who underwent routine ANA testing,16778 were positive for ANA,with a positive rate of 23.37％.Among them,there were 1 708 cases of nucleolar type,accounting for 2.38％of all routine ANA tests,and the proportion of ANA positive cases was 10.18％.There was a statistically significant difference in the positive rate of nucleolar ANA between patients of different genders in the＞20-＜50 year old group and the ≥ 50 year old group(P＜0.05),while there was no statistically significant difference in the positive rate of nucleolar ANA between patients of different genders in the ≤ 20 year old group(P＞0.05).There was a statistically significant difference in the positivity rate of nucleolar ANA among women of different age groups(P＜0.05),among them,the highest positive rate of nucleolar ANA was found in women aged between 20 and 50 years old.There was no statistically significant difference in the positive rate of nucleolar ANA among males of different age groups(P＞0.05).The positivi-ty rate of ANA was the highest among patients in the Department of Rheumatology and Immunology(70.35％),but nucleolar ANA positivity was mainly seen in departments such as Reproductive Medicine Cen-ter(12.90％),Respiratory Medicine(12.40％),and Neurology(11.29％),and the difference in positivity rates between departments was statistically significant(P＜0.05).Out of 1 708 nucleolar ANA positive indi-viduals,420 underwent ANA titers,including 34 AID patients and 386 non AID patients.There was no statis-tically significant difference in nucleolus positive titers between non AID patients and AID patients(P＞0.05).Conclusion The nucleolus type is a common fluorescence pattern in ANA positive individuals,and there are gender and age differences in ANA positive individuals.The positive rate and titer of nucleolar ANA vary among different AID diseases.Combined with other immune function indicators,and it is helpful for early differential diagnosis of AID.

CCTA based clinical value analysis of ΔCT-FFR in evaluating coronary artery function in patients with severe calcification / 解放军医学杂志

Objective To investigate the clinical value of coronary computed tomography angiography(CCTA)based CT derived fractional flow reserve(CT-FFR)and ΔCT-FFR in improving the diagnostic efficiency for coronary abnormal hemodynamics in patients with severe calcification.Methods We retrospectively analyzed the clinical data of coronary artery disease(CAD)patients who underwent CCTA,CT-FFR,invasive coronary angiography(ICA)and FFR during hospitalization from January 2018 to June 2019 in Chinese PLA General Hospital.Severe calcification was defined as coronary artery calcium score(CACS)≥100 on single vessel level.A total of 107 CAD patients with 149 coronary arteries were included in the present study.The enrolled coronary arteries were assigned to CACS≥100 group(n=56)and CACS<100 group(n=93).CT-FFR was performed on the deep FFR platform based on machine learning(ML)algorithms and ΔCT-FFR was defined as CT-FFR difference between proximal and distal to the coronary lesion.The correlation and consistency between CT-FFR and FFR values were analyzed by Pearson and Bland-Altman methods.We attempted to analyze the incremental value of ΔCT-FFR for coronary functional evaluation,especial for coronary arteries with severe calcification,regarding FFR≤0.8 as the diagnostic gold standard.Comparison of receiver operating characteristic curves(ROC)between different diagnostic methods was presented by Delong test.Results Pearson and Bland-Altman analyses showed appreciable correlation(CACS≥100 group,r=0.71,P<0.01;CACS<100 group,r=0.73,P<0.01)and consistency(CACS≥100 group,Mean=-0.01,P=0.25;CACS<100 group,Mean=0,P=0.96)between CT-FFR and FFR values in both groups.FFR(0.80±0.08 vs.0.84±0.09,P=0.004)and CT-FFR(0.81±0.06 vs.0.85±0.06,P<0.001)levels were significant lower in CACS≥100 group than those in CACS<100 group,while ΔCT-FFR(0.14±0.06 vs.0.09±0.06,P<0.001)levels were significant higher in CACS≥100 group.Moreover,the diagnostic efficiency of CT-FFR in CACS≥100 group was inferior to that in CACS<100 group[AUC=0.792(95%CI 0.663-0.889)vs.AUC=0.929(95%CI 0.856-0.972),P=0.04],while it achieved significant improvement after ΔCT-FFR adjustment[AUC=0.876(95%CI 0.760-0.949)vs.AUC=0.792(95%CI 0.663-0.889),P=0.02]and was similar to that in CACS<100 group(P=0.37).Conclusion For coronary arteries with severe calcification,CT-FFR demonstrated significant incremental value in improving the diagnostic efficiency of coronary abnormal hemodynamics after ΔCT-FFR adjustment.

Effects of filament B knockdown on proliferation,migration and apoptosis of mouse MC3T3-E1 cells / 中国组织工程研究

BACKGROUND:Filamin B(FLNB)can crosslink the actin cytoskeleton into a dynamic structure that is essential for the directional movement of cells.It can regulate the proliferation,differentiation and apoptosis of chondrocytes.However,the effect of FLNB on osteoblast proliferation,migration and apoptosis has not been reported. OBJECTIVE:To investigate the effect of FLNB on the proliferation,migration and apoptosis of MC3T3-E1 cells. METHODS:The adenoviral vectors for knockdown of FLNB expression(sh-FLNB1,sh-FLNB2,sh-FLNB3)were constructed and infected with MC3T3-E1 cells.After screened by puromycin drug,the efficiency of FLNB knockdown was detected by western blot and RT-PCR.The MC3T3-E1 cell line with the best efficiency of FLNB knockdown was selected as the stable transient cell line of MC3T3-E1 for subsequent experiments.The cells were divided into blank group,mc3t3 group,sh-NC group(empty vector),and sh-FLNB group(sh-FLNB lentivirus).The blank group was cultured in cell-free α-MEM complete medium;the mc3t3 group was cultured in α-MEM complete medium alone;and the sh-NC and sh-FLNB groups were cultured with α-MEM medium containing 2.5 μg/mL puromycin.After 3 days of culture,cell counting kit-8 assay and cell scratch assay were used to detect the proliferation and migration ability of MC3T3-E1;flow cytometry was used to detect cell apoptosis;and RT-PCR was used to detect the expression of apoptosis-related genes. RESULTS AND CONCLUSION:Western blot and RT-PCR results showed that the efficiency of FLNB knockdown was the best in the sh-FLNB3(P<0.000 1),which was used as a stable cell line for subsequent experiments.Cell counting kit-8 data showed that the proliferative ability of MC3T3 cells was significantly weakened after knockdown of FLNB(P<0.05).Cell scratch assay results showed that the migration ability of MC3T3 cells was significantly decreased after knockdown of FLNB.Flow cytometry and RT-PCR results showed that the apoptotic rate of MC3T3-E1 cells increased after knockdown of FLNB,the expression of pro-apoptotic factor Bax increased significantly,and the expression of anti-apoptotic factor Bcl-2 decreased significantly(P<0.05).To conclude,knockdown of FLNB can reduce the proliferation ability of MC3T3-E1 cells,decrease the migration ability of the cells,and increase cell apoptosis.

Circular RNAs are involved in the pathogenesis of osteoarthritis through intracellular mechanisms / 中国组织工程研究

BACKGROUND:Currently,there is no drug that can completely cure osteoarthritis and its pathogenesis is still unclear.Circular RNAs(circRNAs)are differentially expressed in patients with osteoarthritis and are closely associated with various pathological processes in osteoarthritis.circRNAs play an important role in various physiological and pathological processes,such as chondrocyte homeostasis,extracellular matrix formation,and inflammatory response. OBJECTIVE:To mainly review the effects of circRNAs on pathological factors related to osteoarthritis,as well as the types and expression levels of circRNAs in osteoarthritis. METHODS:Related articles published from 1976 to August 2023 were retrieved from CNKI,WanFang,VIP,PubMed,Medline,Web of Science and Elsevier databases.The keywords were"osteoarthritis,circular RNA,non-coding RNA,synovial tissue,chondrocytes"in Chinese and English,respectively.All the relevant articles were screened,summarized,analyzed,and finally 69 papers were included in the review. RESULTS AND CONCLUSION:circRNAs are non-coding RNAs widely found in eukaryotic cells,with covalently closed continuous loop structure,but with no 5'hat structure and 3'poly A tail,which are involved in multi-gene and multi-target regulatory networks and cannot be degraded by nucleic acid exonucleases(RNase R).circRNAs have a high abundance,high conservativeness and stability,and cell and tissue specificity.circRNAs have biological functions such as acting as molecular sponges for miRNAs,regulating linear RNA transcription and RNA shearing,interacting with RNA-bound proteins,and translating proteins.circRNAs regulate chondrocyte apoptosis and proliferation,degradation of cartilage extracellular matrix,and inflammation and other physiopathologic processes.circRNAs are expected to become biomarkers and potential therapeutic targets for clinical diagnosis and prognosis of osteoarthritis,and may become a new strategy for clinical treatment of osteoarthritis in the future.

The Main Problems and Strategies in the Procurement of Scientific Research Materials and Services in Public Hospitals under the Background of"Streamlining Management and Serving" / 中国卫生经济

The volume of research funding in public hospitals is increasing year by year,with the majority of research funding being used to purchase research materials and services.Traditional offline procurement methods have problems such as inadequate management systems,difficulty in ensuring product quality,blind spots in procurement processes,and high risks in invoice receipt and storage.Public hospitals urgently need to adopt digital methods,introduce research procurement platforms,and implant key control points into the platform based on reshaping the procurement business process,achieve full process supervision and traceability control of research procurement business,and strengthen internal control and risk management of research

The importance and updated key point of ethical review in health management research： based on the Measures of Ethical Review of Life Sciences and Medical Research Involving Humans / 中国医学伦理学

The release of the Measures of Ethical Review of Life Sciences and Medical Research Involving Humans has brought new requirements to the field of ethical review in health management research. Based on the background of new regulations and combining the characteristics of the health management discipline， this paper explored the needs and necessity of ethical review in health management research. In the Measures， the ethical governance of health management research was updated， the concept of exemption from the ethical review was put forward， as well as the importance of protecting the rights and interests of research participants and the protection of personal information were emphasized. This paper also explored the ethical review framework for health management research， including the formulation of operational standards for exemption from ethical review， the refinement of standardized ethical review work systems and processes， and the clarification of information data source verification. These explorations aimed to provide an ethical guarantee for health management research， promote its healthy development， and ensure that the rights and interests of research participants are fully respected and protected. Through research， it is hoped that the ethical level of health management research can be further improved， promoting the development of the discipline and social progress.

Clinical application of radiolabeled FAPIs in non-malignant lesions / 中华核医学与分子影像杂志

Fibroblast activation protein inhibitor (FAPI) has been the focus of nuclear medicine since its introduction. With the in-depth study of FAPI tracer, its clinical application in various non-malignant diseases has also been gradually reported. Many studies have confirmed its uptake in a variety of non-malignant diseases, which indicate that FAPI tracers have good application prospects. This article reviews the latest research status and clinical application of radiolabeled FAPIs in cardiovascular diseases, rheumatic immune diseases, immunoglobulin (Ig)G4-related diseases, renal fibrosis and other non-malignant diseases at home and abroad.

Correlation between serum HbA 1c, γ-GT, ICAM-1 levels and cognitive impairment in elderly patients with hyperlipidemia complicated with cardiovascular diseases / 中华健康管理学杂志

Objective:To analyze the correlation between serum glycated hemoglobin (HbA 1c), γ-glutamyltranspeptidase(γ-GT) and intercellular adhesion factor-1 (ICAM-1) levels and cognitive impairment in elderly patients with hyperlipidemia complicated with cardiovascular disease. Methods:In this retrospective cohort study, 158 elderly patients who underwent examination and were diagnosed with hyperlipidemia complicated with cardiovascular disease at Beijing Anzhen Hospital Affiliated with Capital Medical University from January to December 2022 were selected as study subjects. The simple mental state scale (MMSE) was assessed in the subjects in combination with the subject′s level of education. Illiteracy≤17 points, primary school≤20 points, middle school and above≤24 points were classified as cognitive impairment group (67 cases), the rest were were classified into the non-cognitive impairment group (91 cases); and another 50 healthy elderly people who received physical examination in the same period were selected as the control group. The blood samples in the three groups were extracted to measure serum HbA 1c, γ-GT and ICAM-1. The correlation between HbA 1c, γ-GT and ICAM-1 levels with cognitive impairment were analyzed. Results:The serum levels of HbA 1c, γ-GT and ICAM-1 in the cognitive impairment group were all significantly higher than those in the non-cognitive impairment group and the control group [5.41%±1.04% vs 4.82%±0.95%, 4.39%±0.86%; (52.01±10.96) vs (41.28±9.23), (25.03±7.17) U/L; (336.61±85.36) vs (286.93±72.53), (143.52±64.20) g/ml], and the MMSE score was significantly lower [(20.19±2.85) vs (25.30±1.24), (27.14±1.56) points] (all P<0.05). Serum levels of HbA 1c, γ-GT and ICAM-1 were all significantly negatively correlated with MMSE score ( r=-0.512, -0.498, -0.563) (all P<0.05). The areas under the receiver operating characteristic curves (AUCs) for serum HbA 1c, γ-GT, and ICAM-1 levels in the assessment of cognitive dysfunction were 0.657, 0.816, and 0.691, respectively (all P<0.05). The optimal cut-off values were 5.115%, 47.65 U/L, and 304.58 g/ml, respectively. Conclusion:Serum HbA 1c, γ-GT and ICAM-1 levels in elderly patients with hyperlipidemia complicated with cardiovascular disease are negatively correlated with cognitive impairment, and have certain value for the evaluation and early diagnosis of cognitive impairment.

Chemical constituents from Ganoderma angustisporum and their α-glucosidase inhibitory activities / 中成药

AIM To study the chemical constituents from Ganoderma angustisporum J.H.Xing,B.K.Cui&Y.C.Dai and their α-glucosidase inhibitory activities.METHODS The ethyl acetate extract from G.angustisporum was isolated and purified by silica gel,ODS,TLC and HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.pNPG method was used to evaluate their α-glucosidase inhibitory activities.RESULTS Seven compounds were isolated and identified as N-acetyl-L-phenylalanine ethyl ester(1),N-acetyl-L-phenylalanine methyl ester(2),4-hydroxy-17R-methylincisterol(3),6,8-di-O-methylaverufin(4),aversin(5),methyl 2-(4-hydroxyphenyl)aceate(6),5-toluene-1,3-diol(7).Compounds 1-2,4-7 showed inhibitory activities of α-glucosidase with IC50 values being(33.80±0.47),(45.45±7.95),(48.80±5.86),(39.48±2.82),(41.47±6.68),(55.38±10.12)μmol/L,and compound 1 showed good inhibitory activity.CONCLUSION Compound 1 is a new natural product.Compounds 2-7 are isolated from genus Ganoderma for the first time.Compounds 1-2,4-7 have α-glucosidase inhibitory activities.

Preparation of andrographolide self-microemulsifying drug delivery system / 中成药

AIM To prepare andrographolide self-microemulsifying drug delivery system.METHODS The range of excipient ratio was determined according to equilibrium solubility,excipient compatibility and pseudo-ternary phase diagram.With Pogostemon cablin oil proportion,Labrasol ALF-Tween 80 ratio and Km as influencing factors,drug loading as an evaluation index,the formulation was optimized by central composite design-response surface method,after which in vitro evaluation was performed.RESULTS The optimized formulation was determined to be 10.45%,13.28%,9.82%,66.44%for Pogostemon cablin oil,Labrasol ALF,Tween 80,Transcutol HP proportions,the equilibrium solubility was(11.95±0.04)mg/g.The quality parameters were(20.22±0.38)s for emulsification time,(51.70±2.91)nm for particle size,0.27±0.02 for polydispersity index,and(91.21±1.58)%for light transmission rate,respectively.The self-microemulsion drug delivery system demonstrated good freeze-thaw stability,whose particle size was not obviously influenced by dilution times and dispersion medium,and was rapidly dissolved in phosphate buffer solution(pH 6.8).CONCLUSION Self-microemulsifying drug delivery system can enhance the solubility and dissolution rate of andrographolide.

Effects of group cognitive behavioral therapy on clinical efficacy and executive function in patients with generalized anxiety disorder / 四川精神卫生

BackgroundPrevious studies have found that patients with generalized anxiety disorder （GAD） have impaired performance in executive function， and group cognitive behavioral therapy （CBT） has been shown to be effective in alleviating negative affect in patients with GAD， while its efficacy on executive function remains unclear. ObjectiveTo explore the efficacy of group CBT on anxiety symptom and executive function in GAD patients， so as to provide references for the rehabilitation program for GAD. MethodsA total of 80 consecutive patients with GAD who were hospitalized in Sleep and Psychosomatic Medical Center of Shiyan Taihe Hospital from March 2021 to August 2022 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for GAD were enrolled， and they were assigned into study group （n=40） and control group （n=40） using random number table methods. All patients were subjected to routine medication treatment and regular health education， based on this， study group received group CBT once a week （6 weeks， 60 to 90 minutes per session）. At the enrollment and after 6 weeks of treatment， patients were assessed using Hamilton Anxiety Scale （HAMA） and Frontal Assessment Battery （FAB）. ResultsANOVA with repeated measures on HAMA score revealed a significant time effect （F=1 870.320， P<0.01）， no significant group effect and no significant time×group interaction effect （F=1.254， 0.293， P>0.05）. Significant time effect， group effect and time×group interaction effect were reported on FAB scores （F=311.190， 4.399， 7.021， P<0.05 or 0.01）. Further analysis indicated that FAB scores of both groups after treatment were higher than those at baseline （t=200.569， 115.401， P<0.01）.And the FAB score of study group was higher than that of control group after treatment （t=-3.211， P<0.01）. ConclusionGroup CBT combined with medication treatment for GAD may alleviate the anxiety symptoms and improve executive function in GAD patients. ［Funded by Shiyan Science and Technology Bureau Pilot Scientific Research Project （number， 21Y21）］

Application progress of swept-source optical coherence tomography angiography in ophthalmology / 国际眼科杂志(Guoji Yanke Zazhi)

Swept-source optical coherence tomography angiography(SS-OCTA)is a new vascular imaging technique that was recently proposed. It has the advantages of being non-invasive, quick, high-resolution, and automated vascular stratification imaging. It is extremely helpful in the early diagnosis of ophthalmology-related diseases, as well as in the evaluation of treatment effectiveness and the tracking of disease progression. Based on the foundation of OCTA, SS-OCTA utilizes a fast-tuning laser with a wavelength of 1 050 nm for deeper penetration and non-invasive depth-resolved imaging of the retinal and choroidal microvascular systems, deepening the understanding of the characteristics of a wide range of ophthalmic diseases(fundus lesions, glaucoma, neurodegenerative diseases, etc.). The structures of the anterior segment of the eye can also be studied using SS-OCTA, including changes in the depth and density of corneal neovascularization as well as changes in iris neovascularization before and after therapy. This approach provides a novel tool for ophthalmic clinical practice. The development of the clinical use of SS-OCTA technology in ophthalmology is reviewed in this article.

Trilogy of drug repurposing for developing cancer and chemotherapy-induced heart failure co-therapy agent

Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.