Hypercholesterolemia is pathologically characterized by abnormal accumulation of low-density lipoprotein cholesterol,which is closely associated with metabolic dysfunction-associated fatty liver disease and increased cardiovascular risks.Hepatocytes maintain cholesterol homeostasis through LDL receptor-mediated uptake and esterification storage mechanisms.However,chronic cholesterol overload induces mitochondrial dysfunction,reactive oxygen species accumulation,and endoplasmic reticulum stress,leading to hepatocyte injury.Moreover,systemic hypercholesterolemia disrupts gut microbiota balance and impairs short-chain fatty acid and ketone metabolism,exacerbating metabolic disturbances and aggravating hepatic injury through enhanced metabolic stress.In this article,we review the advance of studies on hypercholesterolemia in recent years and summary its association with hepatic injury,which can provide theoretical support for further research.

This review summarizes the health information needs of patients with brain tumors, covering aspects such as an overview, assessment tools, influencing factors, and intervention support, aiming to provide a reference for developing intervention programs to meet the health information needs of patients with brain tumors.

Hypercholesterolemia is pathologically characterized by abnormal accumulation of low-density lipoprotein cholesterol,which is closely associated with metabolic dysfunction-associated fatty liver disease and increased cardiovascular risks.Hepatocytes maintain cholesterol homeostasis through LDL receptor-mediated uptake and esterification storage mechanisms.However,chronic cholesterol overload induces mitochondrial dysfunction,reactive oxygen species accumulation,and endoplasmic reticulum stress,leading to hepatocyte injury.Moreover,systemic hypercholesterolemia disrupts gut microbiota balance and impairs short-chain fatty acid and ketone metabolism,exacerbating metabolic disturbances and aggravating hepatic injury through enhanced metabolic stress.In this article,we review the advance of studies on hypercholesterolemia in recent years and summary its association with hepatic injury,which can provide theoretical support for further research.

This review summarizes the health information needs of patients with brain tumors, covering aspects such as an overview, assessment tools, influencing factors, and intervention support, aiming to provide a reference for developing intervention programs to meet the health information needs of patients with brain tumors.

Objective We aimed to compared matrix metalloproteinase-13 (MMP-13) and transforming growth factor-β1 (TGF-β1) in synovial fluid,the phosphorylation level of Smad3 in articular cartilage (P-Smad3),and their correlation with traditional Chinese medicine (TCM) patterns in patients with knee osteoarthritis (KOA) of liver-kidney deficiency pattern and pattern of intermingled phlegm and blood stasis.Methods Using a cross-sectional field investigation method,KOA patients hospitalized in the Orthopedics Department of Dongzhimen Hospital,Beijing University of Chinese Medicine from September 2019 to February 2023 were collected. A total of 112 KOA patients were included,among which 63 cases were diagnosed with liver-kidney deficiency pattern,and 49 cases were diagnosed with pattern of intermingled phlegm and blood stasis. The intensity of knee pain,function,and X-ray imaging result were quantified using the Visual Analogue Scale (VAS),Lysholm Knee Scoring Scale,and Kellgren-Lawrence (K-L) Grading Scale,respectively. The TCM pattern was identified and quantified using a TCM Pattern Scoring Scale. Immunohistochemistry was used to determine the phosphorylation characteristics of Smad3 in articular cartilage,and ELISA was used to measure the contents of MMP-13 and TGF-β1 in synovial fluid. The level characteristics and their correlation with the degree of syndrome were analyzed.Results (i) There was no statistically significant difference in VAS scores,Lysholm scores,and K-L grades between KOA patients with different TCM patterns. (ii) Compared with KOA patients with pattern of intermingled phlegm and blood stasis,patients with pattern of liver-kidney deficiency had higher levels of MMP-13 in synovial fluid and lower levels of TGF-β1 in synovial fluid (P<0.05). (iii) In KOA patients with liver-kidney deficiency pattern,there was a positive correlation between the level of MMP-13 in synovial fluid and the score of TCM pattern (r=0.292,P=0.020),while there was a negative correlation between the level of TGF-β1 in synovial fluid and the score of TCM pattern (r=-0.781,P<0.001). In KOA patients with pattern of intermingled phlegm and blood stasis,there was also a positive correlation between the level of MMP-13 in synovial fluid and the score of TCM pattern (r=0.936,P<0.001). (iv) The mean optical density value of P-Smad3 in articular cartilage was lower in KOA patients with liver-kidney deficiency pattern than in pattern of intermingled phlegm and blood stasis (P<0.05).Conclusion KOA patients with liver-kidney deficiency pattern or pattern of intermingled phlegm and blood stasis have different levels of TGF-β1 and MMP-13 in synovial fluid,as well as varying degrees of Smad3 phosphorylation in articular cartilage,which is consistent with the analysis of etiology and pathogenesis under different patterns. The levels of TGF-β1 and MMP-13 in synovial fluid of patients with liver-kidney deficiency pattern can reflect the severity of the pattern to a certain extent,and the mechanism may be related to the inhibition of the activation level of the TGF-β/Smad signaling pathway. This study enriches the research content of the material basis of TCM patterns.

Objective:To identify the chemical constituents of Platycladi Cacumen before and after being carbonized. Method:Chemical constituents in 3 batches of Platycladi Cacumen and its carbonized products were identified and compared by ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry （UHPLC-QTOF-MS/MS）. Chromatographic separation was performed on an ACQUITY UPLC BEH C₁₈ column （2.1 mm×100 mm， 1.7 μm） with 0.1% formic acid aqueous solution （A）- acetonitrile （B） as mobile phase for gradient elution （0-3.5 min， 5%-15%B； 3.5-6 min， 15%-30%B； 6-6.5 min， 30%B； 6.5-12 min， 30%-70%B； 12-12.5 min， 70%B； 12.5-18 min， 70%-100%B； 18-22 min， 100%B）. The flow rate was 0.4 mL·min^-1 and the injection volume was 5 μL. Mass spectrometry was performed by an electrospray ionization， and the primary and secondary mass spectrometry data were collected with the full scan mode of positive and negative ions， the peaks containing MS/MS data were identified by self-established secondary mass spectrometry database and corresponding fragmentation law matching method. Result:A total of 77 and 76 substances with the same change trend were identified under positive and negative ion modes. After being carbonized， the disappeared components of Platycladi Cacumen were mainly amino acids， ketone aldehydes and other volatile components. Among newly produced components， there were 6 kinds of flavonoid aglycones （rhamnetin， 6，7，3'-trihydroxyflavone， 3，6，3'-trihydroxyflavone， 4'-hydroxy-2'-methyl-3，4，5-trimethoxychalcone， herbacetin and 3'，5'-dimethoxy-3，5，7，4'-tetrahydroxyflavone）， 3 kinds of coumarins （7-hydroxycoumarin， 7，8-dihydroxycoumarin and 8-acetyl-7-hydroxycoum-arin） and 3 kinds of benzoic acids （3-methylcatechol， pyrocatechol and chromone-3-carboxylic acid）. There were a total of 40 flavonoids （quercitrin， quercetin， kaempferol， etc.） among these identified chemical constituents. Conclusion:There are significant quantitative and qualitative changes in the chemical compositions of Platycladi Cacumen after being carbonized. The flavonoids， the identified main active ingredients， can provide data reference for further study on the material basis of efficacy changes of Platycladi Cacumen before and after being carbonized.

OBJECTIVES: To construct a cell line that can stably express human phospholamban(PLN) and initially explore its application in the study of myocardial toxicity mechanism. METHODS: FastCloning method was used to insert the open reading frame sequence of target gene PLN into eukaryotic expression vector pcDNA5/FRT/TO(hereinafter referred to as pDFT) to construct the pDFT-PLN-Flag plasmid. The Flp-In^TM T-REx^TM 293 cells were generated by cotransfection of the constructed plasmid and pOG44 plasmid to express the target gene. Successfully recombined monoclonal cell lines were screened by hygromycin B resistance. Western blot and indirect immunofluorescence (IFA) were used to examine the expression of the target protein in recombinant cells. After the cell line was exposed to aconitine, it was verified by Western blot to detect changes in PLN protein phosphorylation. RESULTS: After PCR amplification of the recombinant plasmid and DNA electrophoresis, the length of the amplified product is the same as the known PLN gene fragment, which is consistent with the open reading frame (ORF) sequence of the human PLN gene after sequencing. IFA and Western blot showed that the constructed proliferation cell line can stably express high levels of human PLN under induction and regulation. Preliminary results showed that the phosphorylation level of Thr17-PLN decreased after two hours of exposure to 1 μmol/L aconitine. CONCLUSIONS This human cell line can stably express PLN and can be used to study the mechanism of action of aconitine on the cell at molecular level.
Calcium-Binding Proteins/metabolism* ; Cell Line ; Humans ; Myocardium/metabolism* ; Phosphorylation

Adult ; Asymptomatic Diseases/epidemiology* ; Autoimmune Diseases/etiology* ; China/epidemiology* ; Female ; Humans ; Hypothyroidism/etiology* ; Male ; Metabolic Syndrome/epidemiology* ; Middle Aged ; Obesity/epidemiology* ; Risk Factors ; Thyroid Diseases/etiology* ; Young Adult

In order to effectively solve the over-processing problem of Platycladi Cacumen Carbonisata, which was commonly used as a hemostatic drug in clinical application, we used the quantitative analysis method of multi-components by single marker(QAMS) in this study, with quercetin as internal reference to simultaneously determine the content of six flavonoids which can be used to control the internal quality of Platycladi Cacumen Carbonisata. Based on the comparison of QAMS and external standard method(ESM) results, the limit standards of contents were established as follows: isoquercitroside ≥0.002 0%, quercitroside ≥0.050%, quercetin ≥0.030%, kaempferol and amentoflavone both ≥0.010%, hinokiflavone ≥0.050%. Based on the color detection of Platycladi Cacumen and Platycladi Cacumen Carbonisata with different processing degrees, the law of influence of different processing degrees on the color of Platycladi Cacumen Carbonisata was found. A new external quality standard of Platycladi Cacumen Carbonisata was established by fitting curve of color recognition for the external quality control, based on which the standard ranges of ΔL~*, Δb~* and ΔE were-50.00--44.00, 6.00-11.00 and 45.00-50.00 respectively. Effective combination of established internal and external quality control standards by this study can be used to evaluate the processing degree and quality of Platycladi Cacumen Carbonisata more comprehensively and objectively, which can guarantee its clinical efficacy. At the same time, this study also provides reference and basis for further improving the quality control standard of Platycladi Cacumen Carbonisata.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Flavonoids ; Hemostatics ; Quality Control

Fingerprints of lipophilic components in the roots of Salvia miltiorrhiza and S.yunnanensis were analyzed by UPLC-DADand UPLC coupled with mass spectroscopy to evaluate the differences and similarities of the lipophilic components in the two kinds of herbs.The UPLC analysis of 18 batches of S.miltiorrhiza and 16 batches of S.yunnanensis was performed on a 25℃Thermo Accucore C_(18)column(2.1 mm×100 mm,2.6μm)by Shimadzu LC-20AD;mobile phase was 0.026%phosphoric acid(A)-acetonitrile(B)with gradient elution;flow rate was 0.4 m L·min~(-1);detection wavelength was set at 270 nm;injection volume was 2μL.The molecular structures of the lipophilic components were analyzed on a 25℃Thermo Accucore C_(18)column(2.1 mm×100 mm,2.6μm)by Thermo U3000 UPLC Q Exactive Orbitrap LC-MS/MS with a mobile phaseconsisting of 0.1%formic acid water(A)and 0.1%formic acidacetonitrile(B).The mass spectrometry was acquired in positive modes using ESI.There are 10 common peaks in the lipophilic components of S.miltiorrhiza.The similarity between the 16 batches of S.miltiorrhiza and their own reference spectra was greater than 0.942,and the average similarity was 0.973.There are 12 common peaks in the lipophilic components of S.yunnanensis.The similarity between the 18 batches of S.yunnanensis and their own reference spectra was greater than 0.937,and the average similarity was 0.976.The similarity between the reference chromatograms of S.miltiorrhiza and S.yunnanensis was only 0.900.There are three lipophilic components in S.yunnanensis,which are not found in S.miltiorrhiza,and one of which isα-lapachone.There is a lipophilic component in S.miltiorrhiza not found in S.yunnanensis,which may be miltirone.The two herbs contain 8 common lipophilic components including dihydrotanshinoneⅠ,cryptotanshinone,tanshinoneⅠ,tanshinoneⅡ_A,nortanshinone in which the content of tanshinoneⅡ_A,dihydrotanshinoneⅠand cryptotanshinone of S.yunnanensisis significantly lower than that of S.miltiorrhiza(P<0.01),and the contents of tanshinoneⅠand nortanshinone are significantly lower than that of S.miltiorrhiza too(P<0.05).There are significant differences in the types and contents of lipophilic components between the roots of S.miltiorrhiza and S.yunnanensis,and the similarity between the fingerprints of interspecies is much lower than that between the same species.Therefore,the roots of S.miltiorrhiza and S.yunnanensis are two kinds of herbs which are quite different in chemical compounds and compositions.
Chromatography, Liquid ; Diterpenes, Abietane ; Molecular Structure ; Plant Roots ; Salvia miltiorrhiza ; Tandem Mass Spectrometry