Effect of Cardiac Rehabilitation Nursing on Patients with Myocardial Infarction.

Background: Acute myocardial infarction is the myocardial necrosis caused by acute and persistent ischemia and hypoxia of coronary arteries. It can be complicated with arrhythmia, shock or heart failure, and often can endanger life. The disease is most common in Europe and the United States, where about 1.5 million heart attacks occur each year. China has shown a clear upward trend in recent years, with at least 500 000 new cases and at least 2 million new cases every year. Cardiac rehabilitation nursing is a kind of comprehensive nursing that aims to restore the body function of patients with myocardial infarction. Objective: To explore the therapeutic effect of cardiac rehabilitation nursing in patients with myocardial infarction. Design: This was a case-control retrospective study. Setting: This study was conducted in the Department of Heart Center, Shanghai Sixth People's Hospital. Participants: 86 patients with acute myocardial infarction admitted to the Heart Center of Shanghai Sixth People's Hospital from January 2019 to August 2022 were selected and randomly divided into observation and control groups, with 43 cases in each group. Patients aged from 40-79 years old and were confirmed to have acute myocardial infarction by examination and histopathological analysis. Interventions: The observation group was given cardiac rehabilitation nursing, including psychological nursing, rehabilitation training, cardiac rehabilitation training, diet and defecation care and health education, and the control group was assigned routine nursing. Primary Outcome measures: (1) anxiety and depression were assessed by Zung's self-rating anxiety scale and self-rating depression scale (2) cardiac function was assessed by left ventricular ejection fraction and left ventricular end-diastolic volume (3) 6-minute walk distance (4) incidence of complications (5) length of hospital stay (6) levels of inflammatory factors and N-terminal pro-brain natriuretic peptide concentration (7) incidence of arrhythmia. Results: After the intervention, there was still no significance in either group's left ventricular end-diastolic volume level [(72.24±8.47) vs (71.98±8.35)] (P = .473). However, the anxiety and depression scores [(42.10±5.17) and (44.01±4.53) vs (44.01±4.53) and (51.37±4.85)], complication rate (6.9% vs 16.2%), length of hospital stay [(18.66±7.03) vs (26.11±8.14)], inflammatory factor levels [(1.95±0.51) and (319.47±33.72) vs (2.71±0.45) and (451.07±39.54)], serum N-terminal pro-brain natriuretic peptide level [(2525.8±1236.5) vs (3064.4±859.0)], and incidence of arrhythmia (3 cases, 2 cases, 1 case and 1 case vs 5 cases, 6 cases, 8 cases and 7 vases) in the observation group were lower compared to the control group (P = .000, P = .002, P=0.023, P = .045, P = .032, P = .011, and P = .027). The left ventricular ejection fraction level and 6-minute walk distance of the observation group [(60.39±5.38) and (347.31±21.01) vs (54.97±6.24) and (320.24±21.71)] were better relative to the control group (P = .037 and P = .000). Conclusion: For patients with myocardial infarction, the implementation of cardiac rehabilitation nursing can effectively alleviate the anxiety and depression of patients, decrease the incidence of complications as well as inflammatory factors levels, and further shorten the hospital stay of patients, with high safety. Our study provides a clinical reference for patients with myocardial infarction w who need nursing care.

Uncovering the pharmacological mechanism of Shou Tai Wan on recurrent spontaneous abortion: A integrated pharmacology strategy-based research.

ETHNOPHARMACOLOGICAL RELEVANCE: Shou Tai Wan (STW), a traditional Chinese medicine formula, has been historically used for the treatment of recurrent spontaneous abortion (RSA). Despite its long-standing usage, the exact mechanism underlying the therapeutic effects of STW remains unclear in the existing literature. AIMS OF THIS STUDY: To explore the Pharmacological Mechanism of STW on RSA. METHODS: A network pharmacological methodology was utilized to predict the active compounds and potential targets of STW, collect the RSA targets and other human proteins of STW, and analyze the STW related networks. The animal experiments were also performed to validate the effect of STW on RSA. RESULTS: The results of network analysis showed that STW may regulate PI3K/AKT, MAPK, FoxO signaling pathways and so on. Animal experiment established the RSA model with CBA/J × DBA/2 mice. It was found that STW can reduce the embryo absorption rate of RSA group (p < 0.05) and balance the expression of Th 1/Th2 type cytokines compared with the model group. After 14 days of administration, the decidual and placental tissues were taken and the CD4+ T cells were isolated, and the phosphorylation level of signaling pathway was detected by Springbio720 antibody microarray. This experiment found that STW can significantly up-regulate the phosphorylation levels of STAT3 and STAT6 proteins in the STAT signaling pathway, and down-regulating the phosphorylation level of STAT1 protein. STW also significantly up-regulated the phosphorylation levels of Raf1, A-Raf, Ask1, Mek1, Mek2, JKK1, ERK1, ERK2, c-fos, c-Jun and CREB proteins in the MAPK signaling pathway, and down-regulate the phosphorylation levels of MEK6 and IKKb proteins. Compared with the RSA group, the STW group increased the expression levels of ERK1/2 mRNA and proteins and p-ERK1/2 proteins, and there was a statistical difference (p < 0.05). This is consistent with the chip results. CONCLUSION: STW may achieve therapeutic effects by interfering with the signaling pathways, biological processes and targets discovered in this study. It provides a new perspective for revealing the immunological mechanism of STW in the treatment of RSA, and also provides a theoretical basis for the clinical use of STW in the treatment of RSA.

[Effects of ginger-separated moxibustion at Baliao points combined with Bushen Huoxue formula on patients with decreased ovarian reserve function].

OBJECTIVE: To compare the efficacy differences between ginger-separated moxibustion at Baliao points combined with Bushen Huoxue formula and Bushen Huoxue formula alone on patients with decreased ovarian reserve function. METHODS: Fifty patients of decreased ovarian reserve function were randomly divided into an observation group and a control group, 25 cases in each one. The patients in the observation group were treated with ginger-separated moxibustion at Baliao points combined with Bushen Huoxue formula; the moxibustion was given for 1.5 h, once every seven days, and no treatment was given during menstrual period. The patients in the control group were treated with Bushen Huoxue formula. One-month treatment was taken as one treatment course, and totally three courses were given. The change of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-mullerian hormone (AMH), antral follicle count (AFC), peak systolic velocity (PSV), resistance index (RI) were observed before and after treatment in the two groups. RESULTS: After treatment, the FSH, FSH/LH and RI were significantly lowered, but the E2, AFC, PSV were significantly increased in the two groups (all P<0.05); the FSH, FSH/LH and E2 in the observation group were lower and AFC was higher than those in the control group (all P<0.05). CONCLUSION: The ginger-separated moxibustion at Baliao points combined with Bushen Huoxue formula are superior to Bushen Huoxue formula alone in improving ovarian reserve function.

The isolation and structural elucidation of three new biflavonoid glycosides from Lomatogonium carinthiacum.

Three biflavonoid glycosides, named carinoside B, C and D (1, 2 and 3, respectively), were isolated from the n-BuOH crude extract of the aerial part of Lomatogonium carinthiacum (Wulfen) Rchb (L. carinthiacum). The structures of 1, 2 and 3 were elucidated by spectroscopic methods, including UV, IR, HR-ESI-MS and extensive 1D and 2D NMR techniques.

A biflavonoid glycoside from Lomatogonium carinthiacum (Wulf) Reichb.

A biflavonoid glycoside with a new carbon skeleton, named carinoside A, was isolated from the n-BuOH crude extract of the whole plant of Lomatogonium carinthiacum (Wulf) Reichb. The structure of the new compound was elucidated by using spectroscopic methods, including UV, IR, HR-ESI-MS and extensive 1D and 2D NMR techniques.

Pharmacokinetics-pharmacology disconnection of herbal medicines and its potential solutions with cellular pharmacokinetic-pharmacodynamic strategy.

Recently, there is a global trend of using herbal medicines to treat various chronic diseases and promote health. But the controversy over the safety and efficacy of herbal medicines is a focus of attention, primarily because of the many unknown and unrevealed natures of herbal medicines, which strongly restricts their application and development. Pharmacokinetics is a bridge linking the herbal medicines and their pharmacological responses. It is assumed in traditional pharmacokinetics that an excellent drug should have appropriate pharmacokinetic behaviours and its pharmacological effect is related with plasma drug concentrations. However, most herbal medicines exhibit excellent pharmacological responses despite poor pharmacokinetic behaviours. As most drugs are intracellulartargeted, we put forward cellular pharmacokinetic-pharmacodynamic strategy, which is focused on the intracellular fate of drugs. This strategy could partially explain the marked pharmacological activities of herbal medicines from their intracellular pharmacokinetic behaviours, rather than their plasma concentrations. It is a helpful complementarity to traditional pharmacokinetics, and takes a potential role in the research and development of new herb-origined drugs. In this review, the pharmacokinetics-pharmacology disconnections of herbal medicines (such as ginseng, berberine and danshen) are retrospected. Then our proposed cellular pharmacokineticpharmacodynamic strategy, its characteristics, as well as its research procedures are described, followed by the subcellular distributions of drug transporters and metabolic enzymes which are the determinants of cellular pharmacokinetics-pharmacodynamics. Finally, our successful applications of cellular pharmacokinetic-pharmacodynamic strategy in elucidating ginsenoside Rh2 as an adjuvant agent and tanshinone IIA as an anticancer agent are illustrated.

Lignans from Syringa pinnatifolia Hemsl. Var. alashanensis.

Two new lignans, syripinnalignans A and B (1 and 2), together with two known lignans, were isolated from the stem of Syringa pinnatifolia Hemsl. Var. alashanensis. The structures of 1 and 2 were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques.

Peripheral anti-inflammatory effects explain the ginsenosides paradox between poor brain distribution and anti-depression efficacy.

BACKGROUND: The effectiveness of ginseng in preventing and treating various central nervous system (CNS) diseases has been widely confirmed. However, ginsenosides, the principal components of ginseng, are characterized by poor accessibility to the brain, and this pharmacokinetic-pharmacological paradox remains poorly explained. Anti-inflammatory approaches are becoming promising therapeutic strategies for depression and other CNS diseases; however, previous studies have focused largely on anti-inflammatory therapies directed at the central nervous system. It is thus of interest to determine whether ginsenosides, characterized by poor brain distribution, are also effective in treating lipopolysaccharide- (LPS) induced depression-like behavior and neuroinflammation. METHODS: In an LPS-induced depression-like behavior model, the antidepressant effects of ginseng total saponins (GTS) were assessed using a forced swimming test, a tail suspension test, and a sucrose preference test. The anti-inflammatory efficacies of GTS in brain, plasma, and LPS-challenged RAW264.7 cells were validated using ELISA and quantitative real-time PCR. Moreover, indoleamine 2,3-dioxygenase (IDO) activity in the periphery and brain were also determined by measuring levels of kynurenine/tryptophan. RESULTS: GTS significantly attenuated LPS-induced depression-like behavior. Moreover, LPS-induced increases in 5-HT and tryptophane turnover in the brain were significantly reduced by GTS. IDO activities in brain and periphery were also suppressed after pretreatment with GTS. Furthermore, GTS-associated recovery from LPS-induced depression-like behavior was paralleled with reduced mRNA levels for IL-1ß, IL-6, TNF-α, and IDO in hippocampus. Poor brain distribution of ginsenosides was confirmed in LPS-challenged mice. GTS treatment significantly decreased production of various proinflammatory cytokines in both LPS-challenged mice and RAW264.7 cells. CONCLUSION: This study suggests that the anti-depression efficacy of GTS may be largely attributable to its peripheral anti-inflammatory activity. Our study also strengthens an important notion that peripheral anti-inflammation strategies may be useful in the therapy of inflammation-related depression and possibly other CNS diseases.

Toward a new age of cellular pharmacokinetics in drug discovery.

Pharmacokinetics, pharmacology, and toxicology are the major determinants of the success or failure of candidates during drug development. Because inappropriate pharmacokinetics often leads to inefficacy, even toxicity, pharmacokinetics studies have been regarded as crucial components in drug preclinical and clinical research. However, new data increasingly reveal that drug concentrations in plasma or tissues cannot totally explain the efficacy of drug on the target organ. For most drugs that interact with targets localized in cells, intracellular penetration, accumulation, distribution, and elimination are important parameters governing the efficacy in the target cells. So, there is a pressing need to clarify the cellular pharmacokinetics and thus evaluate the efficacy of drugs in the target cells. This review provides a general overview regarding current knowledge about cellular pharmacokinetics in some specific cells and also summarizes the factors that can influence cellular pharmacokinetics. It concludes by discussing potential strategies for optimizing cellular pharmacokinetics and advocating that global cellular pharmacokinetics studies be conducted in future research toward improving drug efficacy.

Induction of cytochromes P450 1A1 and 1A2 by tanshinones in human HepG2 hepatoma cell line.

Diterpenoid tanshinones including tanshinone IIA (TIIA), cryptotanshinone (CTS), tanshinone I (TI) and dihydrotanshinone I (DHTI) are the major bioactive components from Danshen. The major aim of our present study was to investigate the induction potential of these four main components of tanshinones (TIIA, CTS, TI, and DHTI) on the expression of CYP1A1 and CYP1A2 in HepG2 cells. Our results showed that all of these four tanshinones caused a significant time- and concentration-dependent increase in the amount of CYP1A1/2 expression in HepG2 cells. These induction effects were further characterized through transcriptional regulation: the induction of CYP1A1/2 mRNA level by tanshinones was completely blocked by the transcription inhibitor actinomycin D; the expression of CYP1A1/2 heterogeneous nuclear RNA was induced by tanshinone treatment; and CYP1A1 mRNA stability was not influenced by these tanshinones. Interestingly, tanshinones plus B[a]P produced additive/synergistic effect on CYP1A1/2 induction. In addition, the tanshinone-induced CYP1A1/2 expression was abolished by the aryl hydrocarbon receptor (AhR) antagonist resveratrol, suggesting an AhR dependent transcription mechanism. In the reporter gene assay, while TI and DHTI significantly induced AhR-dependent luciferase activity, TIIA and CTS failed to induce this activity. Collectively, the tanshinones could induce CYP1A1 and CYP1A2 expression through transcriptional activation mechanism and exert differential effects on activating AhR in HepG2 cells. Our findings suggest that rational administration of tanshinones should be considered with respect to their effect on AhR and CYP1A1/2 expression.

20(S)-ginsenoside Rh2 noncompetitively inhibits P-glycoprotein in vitro and in vivo: a case for herb-drug interactions.

P-glycoprotein (P-gp) is an ATP-dependent efflux transporter highly expressed in gastrointestinal tract and multidrug resistance tumor cells. Inhibition or induction of P-gp can cause drug-drug interactions and thus influence the effects of P-gp substrate drugs. Previous studies indicated that 20(S)-ginsenoside Rh2 [20(S)-Rh2] could synergistically enhance the anticancer effects of conventional chemotherapeutic agents at a nontoxic dose. The aim of present study was to investigate in vitro and in vivo whether 20(S)-Rh2 was a P-gp inhibitor and analyze the possible inhibitory mechanisms and potential herb-drug interactions. Results showed that in vitro, 20(S)-Rh2 significantly enhanced rhodamine 123 retention in cells and decreased the efflux ratio of digoxin, fexofenadine, and etoposide, which were comparable to the effects of the established P-gp inhibitor verapamil. However, the transport of 20(S)-Rh2 suggested that 20(S)-Rh2 was not a P-gp substrate. Furthermore, the inhibitory effect persisted for at least 3 h after removal of 20(S)-Rh2. Unlike P-gp substrates, 20(S)-Rh2 inhibited both basal and verapamil-stimulated P-gp ATPase activities. It also significantly decreased UIC2 binding fluorescence, a marker for conformational change of P-gp. In situ and in vivo experiments showed that 20(S)-Rh2 increased the area under the plasma concentration-time curve and maximum plasma concentration of digoxin, fexofenadine, and etoposide significantly without affecting terminal elimination half-time. Long-term treatment with 20(S)-Rh2 failed to affect intestinal P-gp expression in vitro and in vivo. In conclusion, 20(S)-Rh2 is a potent noncompetitive P-gp inhibitor, which indicates a potential herb-drug interaction when 20(S)-Rh2 is coadministered with P-gp substrate drugs. It could increase the absorption of P-gp substrate drugs without long-term induction of P-gp expression in rats.

23-Hydroxybetulinic acid from Pulsatilla chinensis (Bunge) Regel synergizes the antitumor activities of doxorubicin in vitro and in vivo.

UNLABELLED: ETHNOPHARMACOLOGICAL REVELANCE: Pulsatilla chinensis (Bunge)Regel has been used as adjuvant in chemotherapy in traditional Chinese medicine. 23-Hydroxybetulinic acid, an isolated pentacyclic triterpene, is the major active constituent of Pulsatilla chinensis (Bunge) Regel. AIM OF THIS STUDY: To evaluate the combinational anticancer effect of 23-hydroxybetulinic acid and doxorubicin in vitro and in vivo. MATERIALS AND METHODS: The effect of combination treatment with 23-hydroxybetulinic acid and doxorubicin was evaluated with a quantitative combination index method based on the median-effect analysis in various cancer cell lines. And in vivo efficacy of combination chemotherapy was also evaluated using ICR mice bearing sarcoma 180 carcinoma tumors. RESULTS: 23-Hydroxybetulinic acid showed a synergistic cytotoxic effect on multiple cancer cell lines by combined use with doxorubicin. In vivo studies further demonstrated that co-administration of 23-HBA significantly improved the sensitivity of the tumor to doxorubicin through increasing intra-tumor doxorubicin concentration and inhibiting doxorubicin-induced up-regulation of P-gp in tumor. CONCLUSION: These results suggest that the combined therapy with 23-hydroxybetulinic acid and doxorubicin may be a new promising strategy to promote the clinical chemotherapy, which needs further verification.

Diagnostic fragment-ion-based extension strategy for rapid screening and identification of serial components of homologous families contained in traditional Chinese medicine prescription using high-resolution LC-ESI- IT-TOF/MS: Shengmai injection as an example.

The paper presents a modified and universally applicable diagnostic fragment-ion-based extension strategy (DFIBES) to efficiently process the information acquired by liquid chromatography-electrospray ionization source in combination with hybrid ion trap and high-resolution time-of-flight mass spectrometry [LC-(ESI)-IT-TOF/MS], facilitating the structural determination of serial components contained in traditional Chinese medicine prescription (TCMP). The key advantage of DFIBES is that it facilitates the rapid classification of the complicated peaks into well-known chemical families, which significantly simplifies the complicated procedures of structural characterization. Moreover, considering that a certain family of compounds usually produces identical fragment ions, the DFIBES would be widely applicable to many other families of compounds identification besides the presently validated ginsenosides and lignans. Shengmai injection, composed of Panax ginseng, Radix ophiopogonis, and Schisandra chinensis, was taken as a TCMP example to conduct and validate the proposed DFIBES. Diagnostic fragment ions (DFI) for each chemical family contained in Shengmai injection was firstly determined or proposed from the separated analysis of 15 authentic standards and the extract of S. chinensis. The ESI-MSn fragmentation patterns of ginsenosides and lignans were then systematically studied for developing the 'structure extension' approach. Upon LC-IT-TOF/MS analysis and DFIBES, more than 30 ginsenosides and 20 lignans have been rapidly detected and identified from Shengmai injection, supporting that the DFIBES is a very powerful strategy and would be widely applicable for the complicated components identification from TCMP and other complicated mixtures.

[Hypoglyceminc effect of flavonoids from Prinsepia utilis on alloxan-induced diabetic mice].

OBJECTIVE: To evaluate the hypoglycemic effect of flavonoids from Prinsepia utilis Royle in alloxan-induced diabetic mice. METHODS: The hypoglycemic effects were investigated in alloxan-induced diabetic mice after oral administration of 300 mg/kg of flavonoids from Prinsepia utilis Royle for four weeks. The blood glucose (GLU), total cholesterol (TC), triglyceride (TG), very low density lipoprotein cholesterol (VLDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and body weight of mice were determined. RESULTS: Flavonoids from Prinsepia utilis Royle had influence on body weight increasing of diabetic mice in three weeks, but had no influence in the fourth week. Flavonoids from Prinsepia utilis Royle exhibited hypoglycemic effects. Among these fractions, flavonoids from Prinsepia utilis Royle significantly reduced GLU, TG and AST level in diabetic mice compared with model control group (P<0.01), markedly reduced VLDL-C, ALT and BUN level in diabetic mice compared with model control group (P<0.05), but had little influence on TC. CONCLUSION: Flavonoids from Prinsepia utilis Royle possess significant hypoglycemic activities, they can improve hypothepatia of diabetic mice and have protective effect on renal function of diabetic mice.