[Evaluation of efficacy of Dihuang Baoyuan Granules for diabetes mellitus and composition and in vivo distribution analysis based on UHPLC-LTQ-Orbitrap MS].

Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 µm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.

[Study on biomarkers of acteoside in treating puromycin aminonucleoside nephropathy in young rats based on non-targeted urine metabolomics technology].

This study aims to reveal the endogenous metabolic characteristics of acteoside in the young rat model of purinomycin aminonucleoside nephropathy(PAN) by non-targeted urine metabolomics and decipher the potential mechanism of action. Biochemical indicators in the urine of rats from each group were determined by an automatic biochemical analyzer. The potential biomarkers and related core metabolic pathways were identified by ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). MetaboAnalyst 5.0 was used to establish the receiver operating characteristic(ROC) curve for evaluating the clinical diagnostic performance of core metabolites. The results showed that acteoside significantly decreased urinary protein-to-creatinine ratio in PAN young rats. A total of 17 differential metabolites were screened out by non-targeted urine metabolomics in PAN young rats and they were involved in phenylalanine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis. Thirtten differential metabolites were screened by acteoside intervention in PAN young rats, and they were involved in phenylalanine metabolism and arginine and proline metabolism. Among them, leucylproline and acetophenone were the differential metabolites that were significantly recovered after acteoside treatment. These pathways suggest that acteoside treats PAN in young rats by regulating amino acid metabolism. The area under the curve of two core biomarkers, leucylproline and acetophenone, were both greater than 0.9. In summary, acteoside may restore amino acid metabolism by regulating endogenous differential metabolites in PAN young rats, which will help to clarify the mechanism of acteoside in treating chronic glomerulonephritis in children. The characteristic biomarkers screened out have a high diagnostic value for evaluating the treatment of chronic glomerulonephritis in children with acteoside.

[Clinical application value of Huanglian Jiedu Pills in improving syndrome of excess heat and fire toxin based on phase â ¡ clinical trial study on plasma ATP, 4-HNE, and ACTH levels].

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.

[Component profile analysis of Sanhan Huashi Formula based on UHPLC-LTQ-Orbitrap-MS, GC-MS, and UHPLC-QQQ-MS/MS].

This study comprehensively analyzed the active components of Sanhan Huashi Formula using qualitative and quantitative mass spectrometry techniques, laying the foundation for understanding its pharmacological substance basis. UHPLC-LTQ-Orbitrap-MS and GC-MS technologies were used to analyze and identify the volatile and non-volatile components in Sanhan Huashi Formula. UHPLC-QQQ-MS/MS technology was used to simultaneously determine the content of 27 major active components in the formula. The results showed that 308 major chemical components were identified in Sanhan Huashi Formula, among which 60 compounds were identified by comparing with reference standards, mainly including alkaloids, flavonoids, coumarins, triterpenoid saponins, amino acids, and nucleosides. GC-MS technology preliminarily identified 52 volatile compounds, with γ-eudesmol and ß-eudesmol as the main components. The quantitative results demonstrated good linearity(r>0.99) for the 27 active components, indicating the stability, simplicity, and reliability of the established method. Among them, amygdalin, nodakenin, arecoline, ephedrine, and pseudoephedrine had relatively high content and were presumably the main pharmacologically active substances. In conclusion, this study systematically and comprehensively characterized the major chemical components and patterns in Sanhan Huashi Formula, providing a basis for understanding its pharmacological mechanisms and clinical applications.

Recent advances on the role of glia in physiological behaviors: insights from Drosophila melanogaster.

The animal central nervous system is composed of neurons and neuroglia (glia). Extensive research on neurons have shown that they are the major cells to transduce signals in mediating neural development and function, and the glial cells mainly play a role in supporting neurons and maintaining their normal function. Nonetheless, emerging evidence has indicated that glial cells exhibit active roles in virtually all aspects of neuronal function and development. Research using the model organism Drosophila melanogaster reveals that glial cells are key players in the regulation of neural development, nutritional metabolism, sleep, longevity, apoptosis, courtship, smell, learning and memory and other physiological behaviors. In this review, we summarize the research progress of glial cells in regulating different physiological activities in Drosophila, in hope of providing insights on the mechanisms and new prospects on future glial research.

Evaluating the Prognostic Value of the Modified H2FPEF Score in Patients With Heart Failure With Preserved Ejection Fraction.

Background: The H2FPEF score, a convenient tool developed for diagnosing heart failure with preserved ejection fraction (HFpEF), exhibited useful prognostic utility in HFpEF. However, the applicability and the prognostic value of the H2FPEF score in Chinese HFpEF patients have yet to be fully confirmed. The study aimed to evaluate the effect of modified H2FPEF score on the prognosis of Chinese HFpEF patients. Methods: In this retrospective study, we calculated the H2FPEF scores by body mass index (BMI) ≥ 25 kg/m2 and 30 kg/m2 respectively, for 497 consecutive HFpEF patients in China. Subjects were divided into low- (0 - 3 points), intermediate- (4 - 6 points), and high-score (7 - 9 points) groups. The primary and secondary endpoints were heart failure (HF)-related events and acute coronary syndrome (ACS), respectively. Cox proportional hazard models were applied to calculate hazard ratios (HRs). Receiver operating characteristic (ROC) curves and areas under the curve (AUC) were used to evaluate the prediction of the H2FPEF score for adverse outcomes. Results: Over a mean follow-up of 40.46 ± 6.52 months, the primary and secondary endpoints occurred in 168 patients (33.8%) and 97 patients (19.5%), respectively. By the definition of obesity as BMI ≥ 25 kg/m2, a higher incidence of HF-related events and ACS was observed among those with a higher modified H2FPEF score. The modified H2FPEF significantly predicted HF-related events (AUC: 0.723; 95% confidence interval (CI): 0.676 - 0.770; P < 0.001) and ACS (AUC: 0.670; 95% CI: 0.608 - 0.731; P < 0.014) with higher power than the H2FPEF score calculated by BMI ≥ 30 kg/m2. The cutoff of the modified H2FPEF score was 6.5 for detecting HF-related events and ACS. Conclusions: The modified H2FPEF score, using BMI ≥ 25 kg/m2 to define obesity, could more effectively predict the occurrence of subsequent cardiovascular events in Chinese HFpEF patients. The modified H2FPEF score above 6.5 is a risk factor for adverse cardiovascular events in HFpEF patients.

The safety and feasibility of laparoscopic right posterior sectionectomy vs. open approach: A systematic review and meta-analysis.

Background: Laparoscopic right posterior sectionectomy (LRPS) is one of the most technically challenging and potentially hazardous procedures in laparoscopic liver resection. Although some available literature works demonstrated the safety and feasibility of LRPS, these data are limited to reports from a single institution and a small sample size without support from evidence-based medicine. So, we performed a meta-analysis to assess further the safety and feasibility of LRPS by comparing it with open right posterior sectionectomy (ORPS). Methods: MEDLINE, Embase, and Cochrane Library were systematically searched for eligible studies comparing LRPS and open approaches. Random and fixed-effects models were used to calculate outcome measures. Results: Four studies involving a total of 541 patients were identified for inclusion: 250 in the LRPS group and 291 in the ORPS group. The postoperative complication and margin were not statistically different between the two groups (OR: 0.49, 95% CI: 0.18 to 1.35, P = 0.17) (MD: 0.05, 95% CI: -0.47 to 0.57, P = 0.86), respectively. LRPS had a significantly longer operative time and shorter hospital stay (MD: 140.32, 95% CI: 16.73 to 263.91, P = 0.03) (MD: -1.64, 95% CI: -2.56 to -0.72, P = 0.0005) respectively. Conclusion: Data from currently available literature suggest that LRPS performed by an experienced surgeon is a safe and feasible procedure in selected patients and is associated with a reduction in the hospital stay.

[Effect of Xijiao Dihuang Combined Prescription on Human Dendritic Cell Function Induced by Lipopolysaccharide].

OBJECTIVE: To observe the effects of drug-containing serum of Xijiao Dihuang combined prescription(XJDH) on the related functions of dendritic cells(DCs) induced in vitro, and to explore the mechanisms underlying the effectiveness of XJDH treatment on primary immune thrombocytopenia(ITP). METHODS: Peripheral blood samples were colle-ted from 6 healthy volunteers. Mononuclear cells were isolated by density gradient centrifugation, and CD14+ mononuclear cells were collected by the magnetic separation technique. CD14+ mononuclear cells were induced into immature DCs by recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) and recombinant human interleukin 4 (IL-4). Immature DCs were divided into three groups: control group, model group and XJDH group. CCK-8 assay was used to determine the intervention concentration and time of drug-containing serum. Lipopolysaccharide(LPS) with the final concentration of 1 µg/ml was added to model group and XJDH group respectively for 24 h to induce DCs maturation. Normal rat serum was added to control group and model group, and XJDH was added to XJDH group for 24 h. Flow cytometry was used to detect the levels of CD80, CD83 and HLA-DR on the surface of DCs. Western blot was used to detect the expression of TLR4 and NF-κB, and levels of IL-6, IL-12 and TNF-α in cell supernatant was detected by ELISA. RESULTS: Compared with the control group, LPS stimulation increased the expression of CD80, CD83 and HLA-DR, with subsequent increasing expression of TLR4 and NF-κB, as well as IL-6, IL-12 and TNF-α increased(P<0.05). In comparison with model group, the expression of DCs surface molecules CD80, CD83 and HLA-DR, DCs' expression of TLR4 and NF-κB protein, and the levels of IL-6, IL-12 and TNF-α in the cell supernatant of XJDH group decreased after the intervention of XJDH (P<0.05). CONCLUSION: Drug containing serum of Xijiao Dihuang combined prescription can down-regulate TLR4/NF-κB signaling pathway related protein expression, inhibit DCs maturation, and reduce proinflammatory factor secretion, which may be one of the mechanisms of drug-containing serum of Xijiao Dihuang combined prescription in the treatment of immune thrombocytopenia.

Two Novel Mutations (G774A and A1685G) Causing Coagulation Factor XII Deficiency in a Patient with Acute Inferior Myocardial Infarction.

OBJECTIVE: To identify the gene mutation of the coagulation factor XII (FXII) in a patient with FXII deficiency and acute inferior myocardial infarction. METHODS: The proband was a 51-year-old Chinese man who was diagnosed with acute inferior myocardial infarction and had a history of FXII deficiency. The patient presented with a prolonged activated partial thromboplastin time (160 s) and decreased FXII activity (2.3%) and FXII antigen (1%). DNA sequence analysis of the FXII gene was performed by next generation sequencing. The mutant FXII cDNAs were constructed in an expression plasmid vector and transfected into 293T cells. The expression of FXII antigen was detected by western blot. RESULTS: Sequencing of the FXII gene revealed two novel heterozygous mutations, one at exon 8 (G774A; p: W258X) and the other at exon 14 (A1685G; p: D562G). Western blot showed that the FXII antigens were detected only in the supernatant and whole cell lysate of the wild-type and A1685G mutant type, but not in G774A or G774A plus the A1685G mutant type. In addition, the results showed that secretion but not synthesis of A1685G mutant protein was markedly reduced compared to the wild type. CONCLUSION: The present study indicated that the G774A mutation might impair the secretion and synthesis of FXII protein, while the A1685G mutation only influences the secretion of FXII protein. The definition of these new mutations could be useful tools for analyzing the intracellular protein transport and structure-function relationship of FXII protein transport in the future.

Synthesis and evaluation of the antimicrobial activities of 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)-2-thioxothiazolidin-4-one derivatives.

Two novel series of 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)-2-thioxothiazolidin-4-one derivatives were designed and synthesized, and their anti-bacterial activities evaluated. These compounds showed broad-spectrum inhibitory activities against both Gram-positive and Gram-negative bacteria with minimum inhibitory concentration (MIC) values in the range of 1-64 µg/mL. The activity of compound 6c was the more potent with MIC values of 1 µg/mL against the MRSA (3167 and 3506) strains than those of gatifloxacin, oxacillin, and norfloxacin. Compared to the previously reported rhodanine derivatives, 2-thioxothiazolidin-4-one derivatives exhibited an inhibition against Gram-negative strains due to the introduction of a 1,3,4-oxadiazole moiety, among which compounds 3 showed moderate activities against the Gram-negative bacteria (Escherichiacoli 1924) with MIC values of 16 µg/mL.