Mechanism of acupuncture and moxibustion in ameliorating liver injury induced by cisplatin by regulating IRE-1 signaling pathway. / "扶正益肝"é’ˆç¸ç©´æ–¹åŸºäºŽè‚Œé†‡éœ€æ±‚é ¶1ä¿¡å·é€šè·¯æ”¹å–„é¡ºé“‚è‡´å°é¼ è‚æŸä¼¤çš„æœºåˆ¶.

OBJECTIVES: To investigate the mechanism of the effect of acupuncture and moxibustion on improving liver injury in cisplatin (DDP) induced liver injury model mice by observing the changes of inositol-requiring enzyme (IRE) -1 signaling pathway. METHODS: Forty KM mice were randomly divided into control, model, acupuncture and moxibustion groups, with 10 mice in each group. The liver injury model was replicated by intraperitoneal injection of DDP (10 mg/kg). In the acupuncture group and the moxibustion group, acupuncture and moxibustion were performed at "Dazhui"(GV14), and bilateral "Ganshu"(BL18), "Shenshu" (BL23), and "Zusanli"(ST36), respectively for 6 min, once per day for 7 d. The apoptosis of hepatocytes was detected by TUNEL staining. The expression of phosphorylation(p)-IRE-1α, glucose-regulated protein (Grp) 78 and cysteine aspartic protease (Caspase) -12 in liver tissue were detected by immunohistochemistry and Western blot, respectively. The expression levels of Grp78 and Caspase-12 mRNA in liver tissue were detected by quantitative real-time PCR. RESULTS: Compared with the control group, the apoptosis rate of hepatocytes was increased (P<0.05), the positive expression and protein expression of p-IRE-1α, Grp78, and Caspase-12 were increased (P<0.05), the expression levels of Grp78 and Caspase-12 mRNA were increased (P<0.05) in the model group. Compared with the model group, all these indicators showed opposite trends (P<0.05) in the acupuncture and moxibustion groups. CONCLUSIONS: Acupuncture and moxibustion can reduce liver injury due to DDP chemotherapy by modulating IRE-1 signaling pathway, inhibiting the excessive activation of endoplasmic reticulum stress, and reducing liver cell apoptosis.

Breaking down barriers: rationalisations and motivation to stop among Chinese male smokers under cigarette dependence.

BACKGROUND: Smoking rationalisation beliefs are a huge barrier to quitting smoking. What types of rationalisations should be emphasised in smoking cessation interventions? Although past literature has confirmed the negative relationship between those beliefs and motivation to stop smoking, little is known regarding the importance and performance of those beliefs on motivation with varying cigarette dependence. The study aimed to ascertain rationalisations that are highly important for motivation yet perform poorly in different cigarette dependence groups. METHODS: The cross-sectional study was conducted from November 19 to December 9, 2023 in Guiyang City, China. Adult male current smokers were enrolled. Partial least squares structural equation modelling was used to test the hypothesis. The multi-group analysis was used to determine the moderating effect of cigarette dependence, and the importance-performance map analysis was utilised to assess the importance and performance of rationalisations. RESULTS: A total of 616 adult male current smokers were analysed, and they were divided into the low cigarette dependence group (n = 297) and the high cigarette dependence group (n = 319). Except for risk generalisation beliefs, smoking functional beliefs (H1: -ß = 0.131, P < 0.01), social acceptability beliefs (H3: ß = -0.258, P < 0.001), safe smoking beliefs (H4: ß = -0.078, P < 0.05), self-exempting beliefs (H5: ß = -0.244, P < 0.001), and quitting is harmful beliefs (H6: ß = -0.148, P < 0.01) all had a significant positive influence on motivation. Cigarette dependence moderated the correlation between rationalisations and motivation. In the high-dependence group, the social acceptability beliefs and smoking functional beliefs were located in the "Concentrate Here" area. In the low-dependence group, the social acceptability beliefs were also situated in there. CONCLUSIONS: Social acceptability beliefs and smoking functional beliefs showed great potential and value for improvement among high-dependence smokers, while only social acceptability beliefs had great potential and value for improvement among low-dependence smokers. Addressing these beliefs will be helpful for smoking cessation. The multi-group analysis and the importance-performance map analysis technique have practical implications and can be expanded to other domains of health education and intervention practice.

Zinc deficiency deteriorates ovarian follicle development and function by inhibiting mitochondrial function.

Zinc (Zn) is a crucial trace element essential for human growth and development, particularly for reproductive health. Previous research has shown a decrease in serum zinc concentration with age and individuals with conditions such as polycystic ovary syndrome (PCOS) and diabetes mellitus. However, the specific effects of zinc deficiency on the female reproductive system, especially ovarian function, are not fully understood. In our study, we observed a significant reduction in the total number of follicles and mature follicles in the zinc deficiency group. This reduction correlated with decreased level of anti-Mullerian hormone (AMH) and abnormal gene expression affecting hormone secretion regulation. Furthermore, we found that zinc deficiency disrupted mitochondrial dynamics, leading to oxidative stress in the ovaries, which further inhibited autophagy and increased ovarian apoptosis. These changes ultimately resulted in the failure of germinal vesicle breakdown (GVBD) and reduced oocyte quality. Meanwhile, administration of zinc glycine effectively alleviated the oocyte meiotic arrest caused by dietary zinc deficiency. In conclusion, our findings demonstrated that dietary zinc deficiency can affect hormone secretion and follicle maturation by impairing mitochondrial function and autophagy.

A nanopore-based cucumber genome assembly reveals structural variations at two QTLs controlling hypocotyl elongation.

The Xishuangbanna (XIS) cucumber (Cucumis sativus var. xishuangbannanesis) is a semiwild variety that has many distinct agronomic traits. Here, long reads generated by Nanopore sequencing technology helped assembling a high-quality genome (contig N50 = 8.7 Mb) of landrace XIS49. A total of 10,036 structural/sequence variations (SVs) were identified when comparing with Chinese Long (CL), and known SVs controlling spines, tubercles, and carpel number were confirmed in XIS49 genome. Two QTLs of hypocotyl elongation under low light, SH3.1 and SH6.1, were fine-mapped using introgression lines (donor parent, XIS49; recurrent parent, CL). SH3.1 encodes a red-light receptor Phytochrome B (PhyB, CsaV3_3G015190). A ∼4 kb region with large deletion and highly divergent regions (HDRs) were identified in the promoter of the PhyB gene in XIS49. Loss of function of this PhyB caused a super-long hypocotyl phenotype. SH6.1 encodes a CCCH-type zinc finger protein FRIGIDA-ESSENTIAL LIKE (FEL, CsaV3_6G050300). FEL negatively regulated hypocotyl elongation but it was transcriptionally suppressed by long terminal repeats retrotransposon insertion in CL cucumber. Mechanistically, FEL physically binds to the promoter of CONSTITUTIVE PHOTOMORPHOGENIC 1a (COP1a), regulating the expression of COP1a and the downstream hypocotyl elongation. These above results demonstrate the genetic mechanism of cucumber hypocotyl elongation under low light.

Koumine ameliorates neuroinflammation by regulating microglia polarization via activation of Nrf2/HO-1 pathway.

BACKGROUND: Gelsemium elegans (Gardner & Chapm.) Benth (G. elegans) has been widely used as a traditional folk medicine in China and Southeast Asia. As the most abundant alkaloid in G. elegans, Koumine (KM) has been revealed the effect of inflammatory attenuation modulating by macrophage activation and polarization. PURPOSE: This study aimed to explore the effect of KM on modulation of microglia polarization that led to the suppression of neuroinflammation and further improved neurodegenerative behavior. METHODS: Inflammatory mediators, microglia M1 and M2 phenotype markers and Nrf2/HO-1 pathway related protein were assessed in LPS-induced BV2 cells and LPS-treated mice by RT-PCR, immunohistochemistry, immunofluorescence and Western blotting. Moreover, the learning and memory abilities of mice were evaluated by Morris water maze test, and the neuronal damage was evaluated by the Nissl staining. RESULTS: KM attenuated LPS-induced viability and morphological changes in BV2 microglial cells. Our findings showed that KM activated the Nrf2/HO-1 signaling pathway to promote phenotypic switch from M1 to M2 phenotypes. This switch suppresses the release of inflammatory mediators in LPS-induced BV2 cells. Meanwhile, KM attenuated neuroinflammation through modulating microglia polarization and subsequently reversed the behavioral alterations in LPS-induced mice model of neuroinflammation. CONCLUSIONS: KM may alleviate neuroinflammation by regulating microglia polarization with the involvement of Nrf2/HO-1 pathway, resulting of the neuroprotective effect.

[Impact of Climate Warming on Paddy Soil Organic Carbon Change in the Sichuan Basin of China].

Climate warming can increase soil temperature and lead to soil carbon release, but it can also increase soil organic carbon by increasing primary productivity. Cropland soils are considered to have a huge potential to sequester carbon; however, direct observations for the responses of cropland soil organic carbon to climate warming over broad geographic scales are rarely documented. Paddy soil is one of the important cultivated soils in China. Based on the data of 2217 sampling points obtained during the second national soil survey and the data of 2382 sampling points collected during 2017-2019, this study analyzed the change characteristics of soil organic carbon content of paddy surface soil in Sichuan Basin of China and explored the relationships between the soil organic carbon change of paddy soil and temperature, precipitation, cropland use type, fertilization intensity, and grain yield. The results showed that the content of soil organic carbon of paddy soil changed from 13.33 g·kg-1to 15.96 g·kg-1, with an increase of 2.63 g·kg-1, suggesting that soils in the Sichuan Basin have acted as a carbon sink over past 40 years. The soil organic carbon increment of paddy soil varied with different geomorphic regions and different secondary basins. The increase in SOC content in paddy soil was positively correlated with annual average temperature; negatively correlated with annual average precipitation; and initially increased and then decreased with annual average fertilizer application, annual average increase rate of fertilizer application, annual average grain yield, and annual average grain yield growth rate. The relationship between the increase in SOC content and the annual average temperature growth rate was different under different farmland utilizations, and the increase in the annual average temperature growth rate had significant effects with the increase in SOC content only on paddy-dryland rotation. These results indicate that the paddy soil organic carbon change in Sichuan Basin was co-affected by various factors, but climate warming was an important factor leading to the paddy soil organic carbon change, and its influence was controlled by the water conditions determined by farmland use.

Combination of UHPLC-Q Exactive-Orbitrap MS, Bioinformatics and Molecular Docking to Reveal the Mechanism of Huan-Lian-Jie-Du Decoction in the Treatment of Diabetic Encephalopathy.

Diabetic encephalopathy (DE) is a serious complication of diabetes, which affects patients' quality of life. We aimed to explore HLJDD in the treatment of DE by LC/MS and bioinformatics. UPLC-Q Exactive-Orbitrap MS was employed to clarify the compounds. The modules and hub targets of DE were gained from WGCNA. Subsequently, an Herb-Compound-Target network was constructed and enrichment analysis was used. In addition, a protein-protein interaction (PPI) network was constructed and molecular docking was used to verify the above analysis. As result, 138 compounds and 10 prototypes in brain were identified. In network pharmacology, 8 modules and 5692 hub targets were obtained from WGCNA. An Herb-Compound-Target network was constructed by 4 herbs, 10 compounds and 56 targets. The enrichment analysis showed that the treatment of DE with HLJDD involve oxidative stress and neuroprotection. Beside, SRC, JUN, STAT3, MAPK1 and PIK3R1 were identified and as hub targets of HLJDD in treating DE. Moreover, Molecular docking showed that five hub targets had strong affinity with the corresponding alkaloids. Therefore, we explored the underlying mechanisms of HLJDD in the treatment of DE and to provide the theoretical and scientific basis for subsequent experimental studies and clinical applications.

[Advances in Modeling of Multiple Myeloma in Mice].

Multiple myeloma(MM)is a systemic malignancy of plasma cells.Nowadays,the basic research on MM is flourishing with the continuous optimization and innovation of mouse models of MM.Heterologous mouse models of MM established with human-derived cells and immunodeficient mice have been applied in assessing drug efficacy,exploring drug resistance mechanisms,and observing tumor-bone marrow microenvironment interactions.In the last decades,the homologous mouse models of MM established with murine-derived cells or gene-editing technologies have been widely used in the research on the pathogenesis and drug development.Additionally,the stable modeling of targeted organ injury will be a key problem to be tackled in this field.This review summarizes the characteristics and application progress of mouse models of MM.

A national, multicenter, retrospective study of Castleman disease in China implementing CDCN criteria.

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.

[Progress in Chimeric Antigen Receptor-Modified Natural Killer Cells for Multiple Myeloma].

Although the development of novel drugs has significantly improved the survival of patients with multiple myeloma (MM) over the past decades,the lack of effective therapeutic options for relapsed and refractory MM results in poor prognosis.The chimeric antigen receptor (CAR) T-cell therapy has achieved considerable progress in relapsed and refractory MM.Nevertheless,this therapy still has limitations such as cytokine release syndrome,neurotoxicity,and off-target effects.Natural killer (NK) cells,as a critical component of the innate immune system,play an essential role in tumor immunosurveillance.Therefore,CAR-modified NK (CAR-NK) cells are put forward as a therapeutic option for MM.The available studies have suggested that multiple targets can be used as specific therapeutic targets for CAR-NK cell therapy and confirmed their antitumor effects in MM cell lines and animal models.This review summarizes the anti-tumor mechanisms,biological characteristics,and dysfunction of NK cells in the MM tumor microenvironment,as well as the basic and clinical research progress of CAR-NK cells in treating MM.

Nephrotoxicity of immune checkpoint inhibitor combination therapy in patients with advanced renal cell carcinoma: a meta-analysis.

PURPOSE: Few data are available regarding the nephrotoxicity of immune checkpoint inhibitor (ICI) combination therapy in advanced renal cell carcinoma (RCC). This study aimed to investigate the nephrotoxicity of ICI-based combination therapy versus standard of care sunitinib in patients with advanced RCC. METHODS: We searched Embase/PubMed/Cochrane Library for relevant randomized controlled trials (RCTs). Treatment-related nephrotoxicities including increase of creatinine and proteinuria were analyzed by Review Manager 5.4 software. RESULTS: Seven RCTs involving 5239 patients were included. The analysis showed that ICI combination therapy had similar risks of any grade (RR = 1.03, 95% CI: 0.77-1.37, P = 0.87) and grade 3-5 (RR = 1.48, 95% CI: 0.19-11.66, P = 0.71) increased creatinine compared with sunitinib monotherapy. However, ICI combination therapy was associated with significantly higher risks of any grade (RR = 2.33, 95% CI: 1.54-3.51, P < 0.0001) and grade 3-5 proteinuria (RR = 2.25, 95% CI: 1.21-4.17, P = 0.01). CONCLUSIONS: This meta-analysis suggests that ICI combination therapy shows more nephrotoxicity of proteinuria than sunitinib in advanced RCC, which deserves a high attention in the clinic.

Treatment of intrauterine adhesions in rats with hypoxia-cultured BMSC-derived exosomes / 中华妇产科杂志

Objective: To perform intrauterine adhesion modeling, and to investigate the repair effect of hypoxic treated bone marrow mesenchymal stem cells (BMSC) and their derived exosomes (BMSC-exo) on endometrial injury. Methods: BMSC and their exosomes BMSC-exo extracted from rats' femur were cultured under conventional oxygen condition (21%O2) or hypoxia condition (1%O2). Intrauterine adhesion modeling was performed on 40 healthy female SD rats by intrauterine injection of bacterial lipopolysaccharide after curettage. On the 28th day of modeling, 40 rat models were randomly divided into five groups, and interventions were performed: (1) NC group: 0.2 ml phosphate buffered solution was injected into each uterine cavity; (2) BMSC group: 0.2 ml BMSC (1×106/ml) with conventional oxygen culture was injected intrauterine; (3) L-BMSC group: 0.2 ml of hypoxic cultured BMSC (1×106/ml) was injected intrauterine; (4) BMSC-exo group: 0.2 ml of BMSC-exo cultured with conventional oxygen at a concentration of 500 μg/ml was injected into the uterine cavity; (5) L-BMSC-exo group: 0.2 ml hypoxic cultured BMSC-exo (500 μg/ml) was injected intrauterine. On the 14th and 28th day of treatment, four rats in each group were sacrificed by cervical dislocation after anesthesia, and endometrial tissues were collected. Then HE and Masson staining were used to observe and calculate the number of glands and fibrosis area in the endometrium. The expressions of angiogenesis related cytokines [vascular endothelial growth factor A (VEGFA) and CD31], and fibrosis-related proteins [collagen-Ⅰ, collagen-Ⅲ, smooth muscle actin α (α-SMA), and transforming growth factor β1 (TGF-β1)] in endometrial tissues were detected by western blot. Results: (1) HE and Masson staining showed that the number of endometrial glands in L-BMSC group, BMSC-exo group and L-BMSC-exo group increased and the fibrosis area decreased compared with NC group on the 14th and 28th day of treatment (all P<0.05). Noteworthily, the changes of L-BMSC-exo group were more significant than those of BMSC-exo group (all P<0.05), and the changes of BMSC-exo group were greater than those of BMSC group (all P<0.05). (2) Western blot analysis showed that, compared with NC group, the expressions of collagen-Ⅲ and TGF-β1 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group decreased on the 14th and 28th day of treatment (all P<0.05). As the treatment time went on, the expressions of fibrosis-related proteins were different. Compared with BMSC group, the expressions of collagen-Ⅲ, α-SMA and TGF-β1 in the BMSC-exo group and L-BMSC group decreased on the 28th day (all P<0.05). Moreover, the expressions of collagen-Ⅲ and TGF-β1 in L-BMSC-exo group were lower than those in BMSC-exo group on the 28th day (all P<0.05). And the expressions of collagen-Ⅰ, α-SMA and TGF-β1 in L-BMSC-exo group were lower than those in L-BMSC group on the 28th day (all P<0.05). (3) The results of western blot analysis of VEGFA and CD31 showed that, the expressions of VEGFA and CD31 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group increased on the 14th and 28th day of treatment compared with NC group (all P<0.05). Treatment for 28 days, the expressions of VEGFA and CD31 in BMSC-exo group and CD31 in L-BMSC group were higher than those in BMSC group (all P<0.05). Moreover, the expressions of VEGFA and CD31 in L-BMSC-exo group were higher than those in BMSC-exo group and L-BMSC group on the 28th day (all P<0.05). Conclusions: Treatment of BMSC and their exosomes BMSC-exo with hypoxia could promote endometrial gland hyperplasia, inhibit tissue fibrosis, and further repair the damaged endometrium in rats with intrauterine adhesion. Importantly, hypoxic treatment of BMSC-exo is the most effective in intrauterine adhesion rats.

Comparison of active components in different parts of Perilla frutescens and its pharmacological effects / 中国中药杂志

Perilla frutescens is a widely used medicinal and edible plant with a rich chemical composition throughout its whole plant. The Chinese Pharmacopoeia categorizes P. frutescens leaves(Perillae Folium), seeds(Perillae Fructus), and stems(Perillae Caulis) as three distinct medicinal parts due to the differences in types and content of active components. Over 350 different bioactive compounds have been reported so far, including volatile oils, flavonoids, phenolic acids, triterpenes, sterols, and fatty acids. Due to the complexity of its chemical composition, P. frutescens exhibits diverse pharmacological effects, including antibacterial, anti-inflammatory, anti-allergic, antidepressant, and antitumor activities. While scholars have conducted a substantial amount of research on different parts of P. frutescens, including analysis of their chemical components and pharmacological mechanisms of action, there has yet to be a systematic comparison and summary of chemical components, pharmacological effects, and mechanisms of action. Therefore, this study overviewed the chemical composition and structures of Perillae Folium, Perillae Fructus, and Perillae Caulis, and summarized the pharmacological effects and mechanisms of P. frutescens to provide a reference for better development and utilization of this valuable plant.

[Comparison of active components in different parts of Perilla frutescens and its pharmacological effects].

Perilla frutescens is a widely used medicinal and edible plant with a rich chemical composition throughout its whole plant. The Chinese Pharmacopoeia categorizes P. frutescens leaves(Perillae Folium), seeds(Perillae Fructus), and stems(Perillae Caulis) as three distinct medicinal parts due to the differences in types and content of active components. Over 350 different bioactive compounds have been reported so far, including volatile oils, flavonoids, phenolic acids, triterpenes, sterols, and fatty acids. Due to the complexity of its chemical composition, P. frutescens exhibits diverse pharmacological effects, including antibacterial, anti-inflammatory, anti-allergic, antidepressant, and antitumor activities. While scholars have conducted a substantial amount of research on different parts of P. frutescens, including analysis of their chemical components and pharmacological mechanisms of action, there has yet to be a systematic comparison and summary of chemical components, pharmacological effects, and mechanisms of action. Therefore, this study overviewed the chemical composition and structures of Perillae Folium, Perillae Fructus, and Perillae Caulis, and summarized the pharmacological effects and mechanisms of P. frutescens to provide a reference for better development and utilization of this valuable plant.

Advances in Modeling of Multiple Myeloma in Mice / 中国医学科学院学报

Multiple myeloma(MM)is a systemic malignancy of plasma cells.Nowadays,the basic research on MM is flourishing with the continuous optimization and innovation of mouse models of MM.Heterologous mouse models of MM established with human-derived cells and immunodeficient mice have been applied in assessing drug efficacy,exploring drug resistance mechanisms,and observing tumor-bone marrow microenvironment interactions.In the last decades,the homologous mouse models of MM established with murine-derived cells or gene-editing technologies have been widely used in the research on the pathogenesis and drug development.Additionally,the stable modeling of targeted organ injury will be a key problem to be tackled in this field.This review summarizes the characteristics and application progress of mouse models of MM.

Progress in Chimeric Antigen Receptor-Modified Natural Killer Cells for Multiple Myeloma / 中国医学科学院学报

Although the development of novel drugs has significantly improved the survival of patients with multiple myeloma (MM) over the past decades,the lack of effective therapeutic options for relapsed and refractory MM results in poor prognosis.The chimeric antigen receptor (CAR) T-cell therapy has achieved considerable progress in relapsed and refractory MM.Nevertheless,this therapy still has limitations such as cytokine release syndrome,neurotoxicity,and off-target effects.Natural killer (NK) cells,as a critical component of the innate immune system,play an essential role in tumor immunosurveillance.Therefore,CAR-modified NK (CAR-NK) cells are put forward as a therapeutic option for MM.The available studies have suggested that multiple targets can be used as specific therapeutic targets for CAR-NK cell therapy and confirmed their antitumor effects in MM cell lines and animal models.This review summarizes the anti-tumor mechanisms,biological characteristics,and dysfunction of NK cells in the MM tumor microenvironment,as well as the basic and clinical research progress of CAR-NK cells in treating MM.

Similarities and differences of myocardial metabolic characteristics between HFpEF and HFrEF mice based on LC-MS/MS metabolomics / 中华心血管病杂志

Objective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P<0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.

A pair of new isoflavonoid enantiomers from Dalbergia benthamii Prain / 药学学报

Thirteen isoflavones were separated and purified from an ethanol extract of the rhizome of Dalbergia benthamii Prain by using silica gel, Sephadex LH-20, recrystallization et al. Their structures were identified by physicochemical properties and spectral analysis such as MS, 1D/2D-NMR as dalbergibenthamin (1), butesuperin A (2), xanthocercin A (3), butesuperin B (4), di-O-methylalpinum isoflavone (5), 2′-deoxgisoaunculutin (6), robustone (7), 4′-hydroxy-5,7-dimethoxy-6-(3-methyl-2-butenyl)-isoflavone (8), formononetin (9), 6″-O-rhamnosyldaidzin (10), 3′,4′-di-O-methylene-5-hydroxy-7-methoxy-6-isopentenyl isoflavone (11), derrubone dimethyl enter (12), and derrubone (13). Compound 1 is a pair of new isoflavonoid enantiomers, compound 12 is a new natural product and compounds 1-7 and 10-13 were obtained from D. benthamii Prain for the first time. In vitro cytotoxic activities of the compounds were explored by MTS testing with HL-60, A-549, SMMC-7721, MCF-7 and SW480 cell lines. Results show that compound 8 significantly inhibited cellular proliferation. The IC50 of compound 8 in A-549 and SW480 cells was 16.68 ± 0.19 and 15.21 ± 0.60 μmol·L-1.

Challenges and countermeasures of Investigator-Initiated Trial of oncology / 中华医学科研管理杂志

Objective:In order to put forward relevant measures and suggestions to improve the quality of the Investigator-Initiated Trials of oncology in medical institutions.Methods:Through literature research, comparative study, combined with the implementation and management of investigator initiated trials, the current status and challenges of the administration of these trials were analyzed.Results:Investigator-Initiated Trials of oncology become increasingly important. However, its quality is poor compared with Industry-Sponsored Trials due to insufficient funds and lack of effective supervision. Besides, four main challenges as follows were identified: lack of clinical research professionals, the quality concerns of ethical review in some institutions, insufficient funding for clinical research, and imperfect quality management system.Conclusions:Based on the actual needs of IITs of oncology, medical institutions should strengthen the talent cultivation, establish electronic information management platform, increase project support, strengthen scientific research supervision and deepen the awareness of risk prevention to improve the quality of investigator initiated trials.

[The effect of four immunosuppressive drugs on oral manifestations after organ transplantation].

PURPOSE: To assess the prevalence of oral manifestations in a group of allogenic liver, kidney or haematopoietic stem cell transplantation recipients and patients, and analyze the possible oral manifestations associated with the use of 4 immunosuppressive drugs. METHODS: One hundred and eighteen patients submitted to liver, kidney and hematopoietic stem cell transplantation who used tacrolimus， sirolimus，cyclosporine or mycophenolate mofetil were enrolled. Through a questionnaire survey and oral examination, their oral manifestations were recorded, and the possible statistical associations with immunosuppressive drugs were analyzed using SPSS 21.0 software package. RESULTS: The prevalence of oral lichenoid lesions and cheilitis for the group of patients using tacrolimus after transplantation was significantly lower than the group of patients who did not used the agent(P＜0.01). The prevalence of oral lichenoid lesions for the group of patients who used cyclosporine was significantly higher than the group of patients who did not used the drug(P＜0.05), and the prevalence of cheilitis for the group of patients who used cyclosporine was significantly higher than the group of patients who did not used the drug(P＜0.01). The prevalence of oral lichenoid lesions and cheilitis for the group of patients who used tacrolimus was significantly lower than the group of patients who used cyclosporine(P＜0.01). The group of patients who used mycophenolate mofetil after transplantation had a significantly lower prevalence of dry mouth than the group of patients who did not used the drug(P＜0.01). The prevalence of oral manifestations in patients with sirolimus after transplantation was not significantly reduced. CONCLUSIONS: The use of tacrolimus improved the symptoms of oral lichenoid lesions and cheilitis and the effect was better than cyclosporine after transplantation. The use of mycophenolate mofetil improved dry mouth after organ transplantation.