Trastuzumab-induced human cardiomyocyte damage through the Notch2/JAK2/STAT3 pathway

Abstract Objective Trastuzumab is the preferred drug for the treatment of breast cancer. However, research on the cellular mechanisms of trastuzumab's potential cardiotoxicity is insufficient. The purpose of this study was to explore the toxic effects and potential mechanism of action of trastuzumab on cardiomyocytes. Method Human Cardiomyocyte (HCM) viability was assessed using the MTT method. HCM apoptosis was detected using the Hoechst33342/PI Fluorescent staining. The LDH and CK activities of the cell were measured using commercially available LDH and CK assay kits. The expression levels of Notch2, JAK2, STAT3, cleaved caspase 3, bax, and bcl 2 in HCMs were detected using western blotting. Results The results showed that 250 mg/L trastuzumab induced cardiomyocyte injury and apoptosis, inhibited viability, activated the Notch2 receptor, and inhibited JAK2/STAT3 expression in HCM. Inhibition of Notch2 expression in HCM by targeted siNotch2 transfection reversed the trastuzumab-induced injury and apoptosis, and the expression of JAK2/STAT3 returned to normal levels. Conclusions Trastuzumab induces Notch2 expression by inhibiting the JAK2/STAT3 pathway of HCMs, promotes cell apoptosis, and causes cardiomyocyteinjury. Notch2 may be a potential target of trastuzumab-inducedmyocardial injury. This experiment reveals the mechanism of trastuzumab-induced cardiotoxicity, providing a theoretical basis for the application of trastuzumab.

Relationship between Iron Metabolic Parameters and Platelet Counts in Blood Donors / 中国实验血液学杂志

OBJECTIVE@#To investigate the correlation of iron metabolic parameters with platelet counts in blood donors.@*METHODS@#A total of 400 blood donors who met requirements of apheresis platelet donation were collected, and their hematological parameters were analyzed. The donors were divided into low ferritin group and normal group, the differences of hematological parameters between the two groups were compared, and the correlation of iron metabolic parameters and routine hematology parameters with platelet counts were analyzed.@*RESULTS@#Whether male or female, low ferritin group had higher platelet counts than normal group (P < 0.01). Among the iron metabolic parameters, the platelet counts was negatively correlated with serum ferritin (SF), serum iron (SI), and transferrin saturation (TSAT) (r =-0.162, r =-0.153, r =-0.256), and positively correlated with total iron binding capacity (TIBC) and unsaturated iron binding capacity (UIBC) (r =0.219, r =0.294) in female blood donors. Platelet counts was also negatively correlated with SF, SI and TSAT (r =-0.188, r =-0.148, r =-0.224) and positively correlated with UIBC (r =0.220) in male blood donors. Among the routine hematology parameters, platelet counts was negatively correlated with mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and reticulocyte hemoglobin equivalent (Ret-He) in female blood donors (r =-0.236, r =-0.267, r =-0.213, r =-0.284). Platelet counts was also negatively correlated with MCH, MCHC and Ret-He in male blood donors (r =-0.184, r =-0.221, r =-0.209).@*CONCLUSION@#In blood donors with low C-reactive protein level, the lower the iron store capacity, the lower the iron utilization, and the platelet counts tends to rise.

Acupoint compatibility effect: increasing "effect value" and expanding "effect domain" / 中国针灸

By summarizing and exploring the theoretic connotation, key of functions and effect mechanism of acupoint compatibility, the effect of acupoint compatibility is concluded as the increase of "effect value" and the expansion of "effect domain". The increase of "effect value" is the concrete embodiment by the value of medical assessment scale, the value of objective index detection in clinical trial and the value of index detection in experiment research. The expansion of "effect domain" is the increase of effect target and the extension of effect scope. The paper interprets the scientific connotation of acupoint compatibility therapy from a new perspective, and emphasizes the innovative approaches to research while bringing forth new ideas on the research method. It is anticipated that a novel breakthrough can be achieved in the study of acupoint compatibility and the improvement of acupuncture-moxibustion efficacy.

Evaluation of the clinical effect of acupuncture in treatment of neck pain in cervical spondylosis based on propensity score matching / 中国针灸

OBJECTIVE@#To observe the clinical effect and safety of acupuncture in treatment of neck pain due to cervical spondylosis.@*METHODS@#According to the patients' preference and acceptance for the interventions of neck pain induced by cervical spondylosis, an acupuncture group (221 cases) and a non-acupuncture group (251 cases) were divided. After the control of confounding factors with propensity score matching, 218 cases were included in either acupuncture group or non-acupuncture group. In the acupuncture group, acupuncture was applied to Dazhui (GV 14), Baihui (GV 20), ashi points, bilateral neck-Jiaji (EX-B 2), Fengchi (GB 20), Houxi (SI 3), Shenmai (BL 62), etc. The treatment was given once daily, one course of intervention was composed of 5 treatments and 3 courses were included. In the non-acupuncture group, the oral administration of imrecoxib tablets and cobalt tablets was prescribed for 2 weeks. Before and after treatment, the scores of Northwick Park questionnaire (NPQ) and the simplified McGill pain questionnaire (SF-MPQ) were observed, and the safety was assessed in patients of the two groups.@*RESULTS@#After treatment completion, the scores of NPQ and SF-MPQ were all reduced when compared with those before treatment in each group (P<0.001), and the scores of NPQ and SF-MPQ in the acupuncture group were lower than those of the non-acupuncture group (P<0.001). The incidence of adverse reactions was 6.0% (13/218) in the acupuncture group and was 10.1% (22/218) in the non-acupuncture group, without statistical significance in comparison (P>0.05).@*CONCLUSION@#Acupuncture is effective and safe in the relief of neck pain and the improvement of comprehensive quality of life in the patients with cervical spondylosis.

Design, synthesis and evaluation of phenoxyacetic acid-based PTP1B inhibitors / 药学学报

Protein tyrosine phosphatase (PTP) 1B is a potential therapeutic target for type 2 diabetes. Phosphotyrosine (pTyr) mimetics still dominate the currently available PTP1B inhibitors. The phenoxyacetic acid moiety was taken as a pTyr mimetic herein and phenoxyacetic acid-based compounds 2a-2g and 3a-3c were designed. Among them, compounds 2a-2g exhibited potent inhibition against PTP1B, and compound 2g showed an IC50 of 0.42 μmol·L-1 against PTP1B. Compound 2f exhibited pharmacological profiles similar to that of rosiglitazone, and could improve the insulin sensitivity and the serum total cholesterol level. The results suggest that PTP1B inhibitors might be effective in treating type 2 diabetes as well as associated metabolic syndromes.

Establishment and application of activity determining methods for different subtypes of xanthine oxidoreductase / 药学学报

Xanthine oxidoreductase (XOR), the key enzyme catalyzing purine to produce uric acid, including two subtypes, xanthine dehydrogenase (XDH) and xanthine oxidase (XO), respectively, in vivo. Usually, XDH and XO can transform to each other. In this study, based on the principle that the subtype XO or XDH uses different electron acceptors, the methods for the measuring the activities of bovine milk XOR (pure enzyme) and its subtypes were established. The optimal concentrations of substrate xanthine (50 μmol·L-1) and electron acceptor NAD+ (50 μmol·L-1), pH value (7.80) were investigated. The ranges of the XOR, XO, XDH activity which could be determined were 0.97-17.5 U·L-1, 1-9 U·L-1, and 66-1 191 mU·L-1, respectively. Furthermore, the methods for determining the activities of XOR and its subtypes in mouse liver were established. The preparation of liver samples, the optimal concentrations of xanthine (100 μmol·L-1) and NAD+ (100 μmol·L-1) were researched. And the activity ranges of XOR, XO and XDH in mouse liver which could be determined were 0.67-3.98, 0.19-1.08, and 0.52-3.55 U·gprot-1, respectively. With the methods above, the effects of classic XOR inhibitor allopurinal (Allo) on XOR, XO and XDH from both milk and mouse liver were determined. All animal experiments have been approved by the Animal Experimental Center, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College (00003346). This study established new methods for the determination of XOR and its subtypes activity in pure enzyme system and in mouse liver, respectively, which were accurate and convenient. It laid the experimental foundation for exploring the different pathophysiological effects of XOR in the body and developing new XOR inhibitors.

Oxymatrine regulates autophagy through AMPK/mTOR pathway to inhibit OGD/R-induced damage in astrocytes / 中国药理学通报

Aim To investigate the role of autophagy regulated by the AMPK/mTOR pathway in the prevention of oxygen-glucose deprivation/reperfusion injury ( OGD/R) in astrocytes using oxymatrine ( OMT ) . Methods The isolated and purified astrocytes ( AS) were randomly divided into control group ( CON group), OGD/R group and OGD/R + OMT group (0. 1, 0. 2, 0. 4 mmol · L

Research status of related factors affecting the prognosis of central retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

Central retinal vein occlusion(CRVO)is a common retinal vascular disease that severely affects visual acuity. Currently, ranibizumab, aflibercept and dexamethasone implant have been successful in treating macular edema associated with CRVO. However, there were still 1/3 patients with no significant improvement in vision after treatment, 30.7% patients with macular edema subsiding after treatment but recurring, and 28.1% patients with macular edema persisting after treatment. How to determine the prognosis of patients by their different clinical manifestations at the early stage of disease onset can help clinicians to better select treatment options for patients according to their specific disease conditions. Recent studies on the prognosis of CRVO treatment have focused on imaging markers including disorganization of retinal inner layers, retinal hyperreflective foci, subretinal fluid, ischemic index, leakage index, and biomarkers including VEGF, interleukin(IL)-6, IL-8, etc. This article reviews the progress of research on factors related to the prognosis of CRVO, with the aim of treating, managing and monitoring patients with CRVO more precisely and effectively.

Analgesic Effect and Action Mechanisms of Wenjing Zhitong Prescription on Primary Dysmenorrhea / 中国实验方剂学杂志

Objective:To evaluate the analgesic effects of Wenjing Zhitong prescription （WZP） and explore its possible analgesic mechanisms so as to provide experimental basis for research and development of new Chinese medicine. Method:Analgesic effects of WZP were evaluated by observing the writhing latency and number in the writhing models which were induced by oxytocin in rats as well as those induced by acetic acid and prostaglandin E₁ （PGE₁）， respectively in mice. Effect of WZP on uterine contraction frequency， amplitude and activity were evaluated by observing the oxytocin-induced contraction of uterine smooth muscle in rats and rabbits <italic>in vivo</italic>. In the oxytocin-induced rat writhing models， the content of prostaglandin F₂<italic>_α</italic>（PGF₂<italic>_α</italic>） and prostaglandin E₂（PGE₂） in rat uterine tissues and the content of beta-endorphins （<italic>β</italic>-EP） in rat serum were detected by enzyme-linked immunosorbent assay （ELISA）. Expression of estrogen receptor （ER） and oxytocin receptor （OTR） in rat uterine were tested by Real-time polymerase chain reaction（Real-time PCR） method to investigate the possible molecular mechanism of WZP for its analgesic effect. Result:Results of analgesic effect showed that in oxytocin-induced rat writhing experiment， the number of writhing responses in both the WZP （1.5，3.0 g·kg^-1） group was lower than than in the model group （<italic>P</italic><0.05）. In acetic acid-induced mice writhing experiment， the latency of writhing response in WZP （6.0 g·kg^-1） group was significantly prolonged as compared with that in model group <italic>（P</italic><0.01）， and the number of writhing response was significantly reduced （<italic>P</italic><0.05）. In PGE₁-induced mice writhing model， the writhing number in WZP （1.5，3.0，6.0 g·kg^-1） groups was significantly lower than that in the model group （<italic>P</italic><0.05，<italic>P</italic><0.01）. Results of effect on uterine smooth muscle demonstrated that WZP （0.38，0.75，1.50 g·kg^-1） could significantly reduce the frequency of uterine smooth muscle contraction in rabbits （<italic>P</italic><0.05，<italic>P</italic><0.01）， WZP （0.75，1.50，3.00 g·kg^-1） could significantly reduce the contractile amplitude and activity of smooth muscle in the uterus of rats （<italic>P</italic><0.05）. Results of molecular mechanisms of analgesic effects showed that the WZP （0.75，1.50，3.00 g·kg^-1） significantly reduced the content of PGF₂<italic>_α</italic> and the ratio of PGF₂<italic>_α</italic> to PGE₂ in the uterine tissue of rats （<italic>P</italic><0.01）. In the WZP （3.00 g·kg^-1） group， the levels of <italic>β</italic>-EP in the serum of rats were significantly increased （<italic>P</italic><0.01）， and the levels of OTR in uterus of rats in the WZP （1.50，3.00 g·kg^-1） group were significantly decreased （<italic>P</italic><0.05）. Conclusion:Pharmacological studies demonstrated potent analgesic effect of WZP， and such analgesic effect were mediated by significantly inhibiting contraction of uterine smooth muscle， decreasing the contents of PGF₂<italic>_α </italic>and ratio of PGF₂<italic>_α</italic>/PGE₂， reducing OTR expression in uterine as well as increasing the amount of <italic>β</italic>-EP in serum.

The variation of serum uric acid levels among patients with myocardial infarction treated with ticagrelor and the association between serum uric acid and platelet reactivity / 中华心血管病杂志

Objectives: To compare the impact of ticagrelor or clopidogrel on serum uric acid levels among patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) and further evaluate the effects of variation of serum uric acid levels on platelet reactivity. Methods: STEMI patients who admitted to Fuwai Hospital from April 2017 to January 2020, and underwent primary PCI and discharged alive with aspirin and ticagrelor or clopidogrel were included in this study. Patients were divided into ticagrelor group and clopidogrel group. The baseline clinical data were collected. Serum uric acid and creatinine levels at baseline and 30 days post-PCI were measured. Light transmittance aggregometry was used to assess maximum aggregation rate induced by adenosine diphosphate and arachidonic acid. The changes of serum uric acid and creatinine were compared between the two groups. Multivariate logistic regression was performed to evaluate independent related factors for rise in the uric acid levels, and the effect of variation of serum uric acid level on platelet reactivity was analyzed. Results: A total of 967 patients were included, the age was (59.4±12.1) years, and 163 case were female. There were 550 cases in ticagrelor group (56.9%) and 417 cases in clopidogrel group (43.1%). Baseline serum uric acid and creatinine levels were similar between the 2 groups. At 30 days, the serum uric acid level [(347.2±96.5) mmol/L vs. (341.2±105.3) mmol/L, P=0.009] and absolute [46.4 (-2.4, 88.1) mmol/L vs. 25.0 (-21.9, 73.0) mmol/L, P=0.001] and percentage [13.2 (-0.01, 29.0) % vs. 7.9 (-5.7, 25.0) %, P=0.007] increase in the serum uric acid levels were significantly higher in ticagrelor group than in clopidogrel group. The level of serum creatinine at 30 days was significantly lower in ticagrelor group than in clopidogrel group [(89.7±21.3) μmol/L vs. (94.4±43.9) μmol/L, P<0.05], whereas there were no differences in absolute [8.0 (-1.4, 16.6) μmol/L vs. 7.8 (-2.0, 16.6) μmol/L] and percentage [10.5 (-1.7%, 22.6%) vs. 9.8 (-2.4%, 22.1%)] change in the serum creatinine between the 2 groups (all P>0.05). Logistic regression analysis showed that, after adjusting for confounding factors, ticagrelor therapy was an independent related factor of serum uric acid elevation (OR=1.582, 95% CI:1.023-2.447, P=0.039). The variation of the serum uric acid levels did not affect platelet aggregation and the percentage of high platelet reactivity in both groups. Conclusions: Ticagrelor use is related to a significant increase in the serum uric acid levels at 30 days post-PCI in this patient cohort. The variations in the uric acid levels do not increase the percentage of high platelet reactivity in STEMI patients treated with ticagrelor or clopidogrel.

Progress in application of Bletilla striata polysaccharide in novel drug delivery systems and biomaterials / 中国中药杂志

As the main active ingredient of the orchidaceous herb Bletilla striata, B. striata polysaccharide(BSP) has pharmacological activities such as promoting coagulation, anti-inflammation, anti-oxidation, promoting wound healing, anti-tumor, and immunomodulation, and is biodegradable and non-toxic. Additionally, it has the material properties of suspension thickening, film-forming adhesion, coating and solubilizing, targeting and slow releasing, effect-enhancing and toxicity-reducing, etc., playing the role of unification of medicines and excipients. Therefore, BSP has a wide application prospect in the fields of drug delivery system and trauma repair. This paper reviews the research progress of BSP application in new drug delivery systems and biomaterials based on the related li-terature in recent years, with the aim of providing reference for the further research and application of BSP.

Recent studies on the natural products with xanthine oxidase inhibitory effect / 药学学报

Xanthine oxidase (XOD), catalyzing purine metabolism, is the key enzyme in uric acid (UA) biosynthesis, and becomes an important target for hyperuricemia treatment. The inhibition on XOD plays an important role in the treatment of hyperuricemia-related diseases, such as gout, as well as oxidative stress-induced tissue injury. Here, studies on the natural products with XOD inhibition are reviewed.

Swallowing function and its related factors in elderly people in welfare homes of Wenzhou City / 上海预防医学

Objective:To understand the swallowing function of the elderly in welfare homes of Wenzhou City，Zhejiang Province and to analyze the related factors of swallowing dysfunction. Methods:A total of 507 elderly people aged 60 years and over were surveyed by questionnaires in three welfare homes of Wenzhou City from January 2018 to January 2020.Hinds time-limited water drinking test was used to screen dysphagia. Multivariate unconditional logistic regression analysis was used to analyze the related factors of swallowing dysfunction. Results:The incidence of swallowing dysfunction was 26.04% （132 out of 507）. Univariate analysis showed that there were significant differences in the incidence of swallowing dysfunction among the elderly in terms of age， spouse condition， self-care ability， health status， taking sleeping pills， cerebrovascular disease， nervous system disease and depression （P<0.05）. Multivariate logistic regression analysis showed that the following factors were related to swallowing dysfunction among the elderly： age ≥80 years old， taking sleeping pills， cerebrovascular diseases， nervous system diseases and depression. Conclusion:The incidence of swallowing dysfunction in elderly people in welfare homes of Wenzhou City is high， especially those aged ≥80 years who need more attention. In addition， taking sleeping pills， cerebrovascular diseases， nervous system diseases and depression all increase the risk of swallowing dysfunction. Corresponding preventive and intervention measures should be formulated.

The anti-hyperuricemic effects of compound CC18022 targeting xanthine oxidase / 药学学报

Hyperuricemia is not only the biochemical basis of gout, but also closely related to the development of metabolic syndrome, cardiovascular diseases, chronic kidney disease, etc. Xanthine oxidase (XOD) is the key catalytic enzyme for uric acid biosynthesis, therefore the vital target for anti-hyperuricemic drugs. In this study, compound CC18022 was designed and synthesized specifically targeting to XOD. Molecular docking analysis indicated a fairly tight binding between CC18022 and XOD. In the in vitro study, CC18022 significantly inhibited XOD activity with a half maximal inhibitory concentration (IC50) value in the order of nmol·L-1, which is relative to the XOD inhibitor febuxostat. By using both acute and chronic hyperuricemic mice model, compound CC18022 was found to have serum uric acid-lowering effect in a dose-dependent manner in vivo. The animal welfare and experimental processes were in accordance with the provisions of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. In the acute hyperuricemic mice, CC18022 significantly inhibited serum XOD activity, and also the XOD activity in intestine and liver, which were related to purine absorption and metabolism. Therefore, the novel compound CC18022 exhibited significant inhibition on XOD activity and anti-hyperuricemic effects, making it a favorable candidate for further research.

Dynamic change of hippocampal volume in children with recurrent febrile seizures / 中国当代儿科杂志

OBJECTIVE@#To study the change and significance of hippocampal volume (HCV) in children with recurrent febrile seizures.@*METHODS@#A retrospective analysis was performed on the medical data and examination results of 34 children with recurrent febrile seizures who underwent two magnetic resonance plain scans of the head and the hippocampus from January 1, 2013 to September 30, 2019. According to the follow-up time, they were divided into the first follow-up group and the second follow-up group. According to prognosis, they were divided into a febrile seizure group, a non-febrile group and an epilepsy group. The change in HCV was analyzed and compared.@*RESULTS@#Total HCV was positively correlated with age (@*CONCLUSIONS@#HCV gradually increases with age in children with recurrent febrile seizures. Persistent seizures may damage the development of the hippocampus.

Flourishing Epitranscriptomics Research / 中国生物化学与分子生物学报

So far, researchers have found more than one hundred different kinds of chemical modifications on RNA. Most of these modifications are distributed on high abundant non-coding RNAs and are important for maintaining the functions of these non-coding RNAs. In recent years, thanks to the application of high-resolution mass spectrometry and the development of whole-transcriptome sequencing technologies, more and more modifications on mRNA have been discovered, and accurately mapped and localized, including N

Comparative Study on Hepatotoxicity of Psoraleae Fructus in Rats and Mice / 中国实验方剂学杂志

Objective:Arrange long-term toxicity experiments by a uniform design method， so as to explore the effect of different extracts of Psoraleae Fructus on liver toxicity in rats and mice， and find the drug factors that cause psoralen liver toxicity. Method:Based on the factors of processing， extraction technology， dosage and treatment course， each experimental group was arranged by uniform design method. A total of 220 SD rats and 220 Kunming mice with half male and half female were divided into normal groups and drug groups 1 to 8. The corresponding drugs （50% alcohol extract of salt Psoraleae Fructus in rats 2.57 g·kg-1， mice 5.14 g·kg-1， 95% alcohol extract of Psoraleae Fructus in rats 0.51 g·kg-1， mice 1.02 g·kg-1， 70% alcohol extract of salt Psoraleae Fructus in rats 1.71 g·kg-1， mice 3.42 g·kg-1， water extract of Psoraleae Fructus in rats 1.03 g·kg-1， mice 2.06 g·kg-1， water extract of salt Psoraleae Fructus in rats 1.03 g·kg-1， mice 2.06 g·kg-1， 70% alcohol extract of Psoraleae Fructus in rats 1.71 g·kg-1， mice 3.42 g·kg-1， 95% alcohol extract of salt Psoraleae Fructus in rats 0.51 g·kg-1， mice 1.02 g·kg-1， 50% alcohol extract of Psoraleae Fructus in rats 2.57 g·kg-1， mice 5.14 g·kg-1） were administered by gavage daily. The body weight and food intake of the rats and mice were measured once a week. After the treatment course， the rats were anesthetized with sodium pentobarbital， and blood was taken from the abdominal aorta， and the mice were sacrificed by removing the eyeballs， and the liver and brain were taken to calculate the organ coefficients. Serum was taken to determine liver function-related indicators， and the liver was taken for histopathological examination by hematoxylin-eosin （HE） staining. Result:The liver visceral-brain ratio of female rats in group 3 were significantly increased （P<0.05）. The liver quality， visceral-body ratio and visceral-brain ratio of male mice in groups 1 to 3 were significantly increased （P<0.05， P<0.01）. Histopathological manifestations in mice were more obvious than those in rats. Histopathology showed hepatocyte hypertrophy in the central area of liver lobules in mice， in particular in group 3. According to the multiple regression equation， there were interactions between extraction technology， processing， dosage and treatment course， and the extraction technology was positively correlated with the pathological score of liver injury. Based on the results of visual analysis and other indicators， it is concluded that the extraction technology factor is most relevant to psoralen liver toxicity of Psoraleae Fructus. Conclusion:Psoraleae Fructus has the hepatotoxicity， which is related to ethanol extraction technology； alcohol extraction is more toxic than water extraction， and 70% ethanol extraction is the most toxic. Besides， there are species differences， with a more significant hepatotoxicity in mice than that in rats.

Heat-Clearing Chinese Medicines in Lipopolysaccharide-Induced Inflammation / 中国结合医学杂志

Lipopolysaccharide (LPS)-induced inflammation causes massive threatening diseases, such as sepsis, acute lung injury and multiple organ dysfunction syndrome. Efficient treatment to prevent inflammation is crucial in LPS-induced inflammatory diseases. Heat-clearing Chinese medicines (CMs) have been used to ameliorate LPS-induced inflammation in China for centuries. Heat-clearing CMs regulate inflammatory pathways, thereby inhibiting the release of inflammatory factors. This review aimed to introduce promising heat-clearing CMs countering LPS-induced inflammation in the last 5 years, exploring the underlying molecular mechanisms.

Antioxidant and Antiapoptotic Polyphenols from Green Tea Extract Ameliorate CCl-Induced Acute Liver Injury in Mice / 中国结合医学杂志

OBJECTIVE@#To investigate the phenolic composition, antioxidant properties, and hepatoprotective mechanisms of polyphenols from green tea extract (GTP) in carbon tetrachloride (CCl)-induced acute liver injury mouse model.@*METHODS@#High-performance liquid chromatography was used to analyze the chemical composition of the extract. Antioxidant activity of GTP was assessed by O, OH, DPPH, and ferric-reducing antioxidant power (FRAP) assay in vitro. Sixty Kunming mice were divided into 6 groups including control, model, low-, medium-, and high-doses GTP (200, 400, 800 mg/kg) and vitamin E (250 mg/kg) groups, 10 in each group. GTP and vitamin E were administered at a level of abovementioned doses twice per day for 7 days prior to exposure to a single injection of CCl. Hepatoprotective effects of GTP were evaluated in a CCl-induced mouse model of acute liver injury, using commercial enzyme linked immunosorbent assay kits, histopathological observation, terminal deoxynucleotidyl transferase-mediated dUTPNick-end labeling (TUNEL) assay and Western blot.@*RESULTS@#GTP contained 98.56 µg gallic acid equivalents per milligram extract total polyphenols, including epicatechingallate, epigallocatechin gallate, epicatechin, and epigallocatechin. Compared with the model group, low-, medium-, or high doses GTP significantly decreased serum levels of alanine aminotransferase and aspartate transaminase (P<0.01). Histopathological observation confirmed that pretreatment of GTP prevented swelling and necrosis in CCl-exposed hepatocytes. Hepatoprotective effects of low-, medium-, and high-dose GTP were associated with eliminating free radicals and improving superoxide dismutase, catalase, and glutathione peroxidase activity in the liver. Additionally, low-, medium-, and high-dose GTP decreased cell apoptosis in the CCl-exposed liver (P<0.01). Phosphorylated nuclear factor kappa-B (NF-κB), p53, Bcl-2 associated x protein/B-cell lymphoma/leukemia-2 gene, cytochrome C, and cleaved caspase-3 levels were downregulated compared with the model group (P<0.01).@*CONCLUSION@#GTP achieves hepatoprotective effects by improving hepatic antioxidant status and preventing cell apoptosis through caspase-3-dependent signaling pathways.

Associations between postprocedural D-dimer, hs-CRP, LDL-C levels and prognosis of acute myocardial infarction patients treated by percutaneous coronary intervention / 中华心血管病杂志

Objective: To investigate the association between postprocedural D-dimer, high sensitivity C-reactive protein(hs-CRP) and low-density lipoprotein-cholesterol(LDL-C) and outcomes of acute myocardial infarction (AMI) patients treated by percutaneous coronary intervention(PCI), in order to clarify the impacts of thrombotic, inflammatory and cholesterol risks on long-term prognosis. Methods: Patients with AMI who underwent emergency PCI from January 2010 to June 2017 in Fuwai Hospital with complete baseline data were enrolled. Patients were stratified into four groups according to quartiles of D-dimer, hs-CRP and LCL-C. Cox regression was used to analyze the relationship between these biomarkers and prognosis. Restricted cubic spline (RCS) was used to characterize the continuous association between risk of all-cause death and biomarkers. The primary outcome was all-cause death. Results: A total of 3 614 patients were included in the analysis. The age was (59.2±12.0) years old, and 2 845 (78.7%) were male and 3 161 (87.5%) patients were diagnosed as ST-segment elevation myocardial infarction. The follow-up time was 652 (414, 1 880) days. Survival analysis showed that postprocedural D-dimer and hs-CRP were significantly associated with all-cause mortality (all P<0.05). Cox regression with multiple adjustments showed that patients with D-dimer≥580 μg/L presented higher risk of all-cause death (HR=2.03, 95%CI 1.22-3.38, P=0.006), compared to patients with D-dimer<220 μg/L. RCS analysis showed that risk of all-cause death was stably high when D-dimer reached 500 μg/L. Multivariable Cox regression also showed that patients with hs-CRP<2.74 mg/L (HR=1.86, 95%CI 1.10-3.15, P=0.020)or hs-CRP≥11.99 mg/L (HR=2.14, 95%CI 1.35-3.40, P=0.001) presented higher mortality compared to patients whose hs-CRP was 2.74-7.18 mg/L. RCS analysis indicated a J-shaped relation between hs-CRP and mortality, as greater risk of death was observed when hs-CRP was lower than 2 mg/L or higher than 10 mg/L. LDL-C was not associated with outcomes (all P>0.05). Conclusions: Postprocedural D-dimer is significantly associated with long-term prognosis of AMI patients treated by PCI. Patients with extremely high or low levels of hs-CRP presents worse outcomes. Intensive and tailored antithrombotic or anti-inflammatory therapies should be considered for patients with increased thrombotic risk and those with extremely high or low inflammatory risk.