System analysis of Huang-Lian-Jie-Du-Tang and their key active ingredients for overcoming CML resistance by suppression of leukemia stem cells.

BACKGROUND: BCR-ABL1-based resistance to imatinib, mainly resulting from BCR-ABL1 mutations, is largely solved after second- and third-generation tyrosine kinase inhibitors (TKIs) are discovered. Nonetheless, imatinib resistance without BCR-ABL1 mutations, including intrinsic resistance induced by stem cells within chronic myeloid leukemia (CML), remains the major clinical challenge for many patients. PURPOSE: To study the key active ingredients and corresponding target proteins in Huang-Lian-Jie-Du-Tang (HLJDT) against BCR-ABL1-independent CML resistance to therapeutics, and then explore its mechanism of against CML drug resistance. METHODS: Cytotoxicity of HLJDT and its active ingredients in BCR-ABL1-independent imatinib resistance cells was analyzed through MTT assay. The cloning ability was measured through soft agar assay. Monitoring therapeutic effect on Xenografted mice CML model by in vivo imaging technology and mice survival time. Predicting the potential target protein binding sites by the technology of photocrosslinking sensor chip, molecular space simulation docking, and use Surface Plasmon Resonance (SPR) technology . Flow cytometry to detect the ratio of stem progenitor cells (CD34+). Constructing bone marrow transplantation mice CML leukemia model, detect the effects on leukemia stem cells LSK (Lin-\ Sca-1+ \C-kit+) self-renewal. RESULTS: Treatment with HLJDT, berberine and baicalein inhibited cell viability and colony formation of BCR-ABL1-independent imatinib-resistant cells in vitro while prolonging survival in mouse with CML xenografts and transplatation CML-like mouse models in vivo. JAK2 and MCL1were identified as targets of berberine and baicalein. JAK2 and MCL1 are involved in multi-leukemia stem cell-related pathways. Moreover, the ratio of CD34+ cells in resistant CML cells is higher than in treatment-sensitive CML cells. Treatment with BBR or baicalein partially suppressed CML leukemic stem cells (LSCs) self-renewal in vitro and in vivo. CONCLUSION: From the above, we concluded that HLJDT and its key active ingredients (BBR and baicalein) allowed to overcome imatinib resistance with BCR-ABL1 independent by eradication of LSCs by targeting the JAK2 and MCL1 protein levels. Our results lay the foundation for applying HLJDT in patients with TKI-resistant CML.

Targeting ABCB6 with nitidine chloride inhibits PI3K/AKT signaling pathway to promote ferroptosis in multiple myeloma.

Since multiple myeloma (MM) remains a cureless malignancy of plasma cells to date, it becomes imperative to develop novel drugs and therapeutic targets for MM. We screened a small molecule library comprising 3633 natural product drugs, which demonstrated that Nitidine Chloride (NC), an extract from traditional Chinese medicine Zanthoxylum nitidum. We used Surface Plasmon Resonance-High Performance Liquid Chromatography-Protein Mass Spectrometry (SPR-HPLC-MS), Cellular Thermal Shift Assay (CETSA), molecular docking, and SPR assay to identify the potential targets of NC, in which ABCB6 was the unique target of NC. The effects of ABCB6 on cellular proliferation and drug resistance were determined by CCK8, western blot, flow cytometry, site-mutation cells, transmission electron microscopy, immunohistochemistry staining and xenograft model in vitro and in vivo. NC induced MM cell death by promoting ferroptosis. ABCB6 is the direct target of NC. ABCB6 expression was increased in MM samples compared to normal controls, which was significantly associated with MM relapse and poor outcomes. VGSK was the inferred binding epitope of NC on the ABCB6 protein. In the ABCB6-mutated MM cells, NC did not display cancer resistance, implying the vital role of ABCB6 in NC's bioactivity. Moreover, the silencing of ABCB6 significantly inhibited MM cell growth. Mechanistically, the direct binding of NC to ABCB6 suppressed PI3K/AKT signaling pathway to promote ferroptosis. In conclusion, ABCB6 can be a potential therapeutic target and prognostic biomarker in MM, while NC can be considered a novel drug for MM treatment.

Discovery of the oncogenic MDM2, a direct binding target of berberine and a potential therapeutic, in multiple myeloma.

Recent studies have suggested the potency of berberine (BBR) for multiple cancer treatments, including multiple myeloma (MM). However, the direct target and underlying mechanism of BBR remain largely understood in MM. Here, we demonstrated that BBR inhibited cell proliferation and acted synergistically with bortezomib in MM.1S cells. BBR treatment induced MM cell cycle arrest by downregulating several cell cycle-related proteins. Murine double minute 2 (MDM2) as a BBR-binding protein was identified by surface plasmon resonance image (SPRi) analysis and molecular docking. Overexpression of MDM2 is associated with MM progression and a poor prognosis. Knockdown MDM2 by siRNA transfection can repress MM malignant progression and attenuate the BBR sensitivity to MM.1S cells. BBR treatment induced the degradation of MDM2 through the ubiquitin-proteasome system and reactivated P53/P21 in MM cells. Overall, our data has illustrated that MDM2, as a binding protein of BBR for the first time, may serve as a potential therapeutic option for MM.

PLA2 mediates the innate immune response in Asian corn borer, Ostrinia furnacalis.

The eicosanoid signaling pathway mediates insect immune reactions to a wide range of stimuli. This pathway begins with the biosynthesis of arachidonic acid (AA) from the hydrolysis of phospholipids catalyzed by phospholipase A2 (PLA2 ). We report here that the PLA2 inhibitor, dexamethasone (DEX), impaired the innate immune response including nodulation, encapsulation, and melanization in Ostrinia furnacalis larvae, while AA partially reversed these effects of DEX. We cloned a full-length complementary DNA encoding a PLA2 , designated as OfsPLA2 , from O. furnacalis. The open reading frame of OfsPLA2 encodes a 195-amino acid residue protein with a 22-residue signal peptide. Sequence alignment analyses indicated that O. furnacalis PLA2 might be a Group III secretory PLA2 . The highest transcript levels of OfsPLA2 were detected in the fat body, and its transcript levels increased dramatically after infection with Escherichia coli, Micrococcus luteus, or Beauveria bassiana. Recombinant OfsPLA2 significantly induced prophenoloxidase (PPO) activation in larval hemolymph in the presence of Ca2+ and encapsulation of agarose beads. Injection of recombinant OfsPLA2 into larvae resulted in increased transcript levels of attacin, defencin, and moricin-3 genes. Our results demonstrate the involvement of the eicosanoid signaling pathway in the innate immune response of O. furnacalis larvae and provide new information about the roles of O. furnacalis secretory PLA2 in activating PPO and antimicrobial peptide production.

Identification of adducts formed between acrolein and alanine or serine in fried potato crisps and the cytotoxicity-lowering effect of acrolein in three cell lines.

In physiological and thermally-processed conditions, alanine and serine efficiently eliminate acrolein to generate two main adducts, 2-(5-formyl-3,6-dihydropyridin-1(2H)-yl) propanoic acid and 2-(5-formyl-3,6-dihydropyridin-1(2H)-yl)-3-hydroxypropanoic acid, with amounts of 81.6 ± 4.24 µg/kg and 23.72 ± 0.40 µg/kg in fried potato crisps, respectively. Adduct formation markedly decreased the cytotoxicity of acrolein against Caco-2, GES-1 and HUVEC cells. The cell viability of them remained approximately100% after incubation with 200 µmolL-1 adducts, while the IC50 values for acrolein in the three cells were 66, 54, and 16 µmolL-1 respectively. The adducts express the protective effects by tremendous reduction of cell apoptosis, reactive oxygen species (ROS) production, and DNA damage.

What Is the Role of Pharmacists in Treating COVID-19 Patients? The Experiences and Expectations of Front Line Medical Staff.

Aims: The study aimed to understand the role and the core values of pharmacists and the professional expectations of medical staff for pharmacists in treating COVID-19 patients from the perspectives of the frontline medical staff. The findings help to understand and provide a reference for the career growth path of future pharmacists. Methods: A phenomenological method was used to conduct in-depth interviews with frontline medical staff working in isolation wards during COVID-19. The interview data were analyzed, and the themes were extracted. Results: Pharmacists played a positive role in ensuring the supply of non-routinely stocked drugs, including traditional Chinese medicine preventative preparations, providing drug information and medication consultation for complex patients, and identifying adverse drug reactions. However, at present, the integration of pharmacists and nurses is poor with inadequate communication, and the pharmaceutical care activities provided to physicians were still not comprehensive. Conclusions: The level of pharmaceutical care provided by pharmacists needs to be further strengthened. Frontline medical teams generally have high professional expectations for pharmacists, including expecting pharmacists to become drug therapy experts. They expect pharmacists to fully participate in clinical decision-making, especially playing a central role in managing drug interactions, contraindications, and other clinical uses of drugs.

Identification of berberine as a novel drug for the treatment of multiple myeloma via targeting UHRF1.

BACKGROUND: Current therapies for multiple myeloma (MM) are associated with toxicity and resistance, highlighting the need for novel effective therapeutics. Berberine (BBR), a botanical alkaloid derived from several Berberis medicinal plants, has exhibited anti-tumor effects, including against multiple myeloma (MM); however, the molecular mechanism underlying the anti-MM effect has not been previously described. This study aimed to identify the target of berberine and related mechanisms involved in its therapeutic activity against MM. RESULTS: Here, we demonstrated that BBR treatment killed MM cells in vitro and prolonged the survival of mice bearing MM xenografts in vivo. A screening approach integrating surface plasmon resonance (SPR) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified UHRF1 (ubiquitin-like with PHD and RING Finger domains 1) as a potential target of BBR. Combining molecular docking and SPR analysis, we confirmed UHRF1 as a BBR-binding protein and discovered that BBR binds UHRF1 in the tandem tudor domain and plant homeodomain (TTD-PHD domain). BBR treatment induced UHRF1 degradation via the ubiquitin-dependent proteasome system and reactivated p16INK4A and p73 in MM cells. Overexpression of UHRF1 promoted the MM cell proliferation and rendered MM cells more resistant to BBR, while silencing of UHRF1 with siRNA attenuated BBR-induced cytotoxicity. CONCLUSIONS: In summary, our study has identified UHRF1 as a direct target of BBR and uncovered molecular mechanisms involved in the anti-MM activity of BBR. Targeting UHRF1 through BBR may be a novel therapeutic strategy against MM.

Therapeutic observation on herbal cake-partitioned moxibustion for dysmenorrhea due to deficiency cold / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of herbal cake-partitioned moxibustion for dysmenorrhea due to deficiency cold. Methods: A total of 70 patients with dysmenorrhea who met the inclusion criteria were randomized into a mild moxibustion group and a herbal cake-partitioned moxibustion group by the random number table, with 35 cases in each group. Shenque (CV 8), Zhongji (CV 3) and bilateral Zigong (EX-CA 1) were selected for both groups. The treatment continued for 3 menstrual cycles. The visual analog scale (VAS) and COX menstrual symptom scale (CMSS) were scored in both groups before treatment, after treatment and at the end of the 3rd menstrual cycle after treatment. The clinical efficacy was evaluated at the end of the 3rd menstrual cycle after treatment. Results: After treatment, the clinical efficacy of the herbal cake-partitioned moxibustion group had the tendency to be superior to that of the mild moxibustion group, while there was no statistically significant difference in the overall efficacy between the two groups (P>0.05). The VAS and CMSS scores after treatment and at the follow-up were significantly lower than those before treatment in both groups (all P<0.05). At the follow-up, the VAS scores in both groups had no significant intra-group differences from those after treatment (both P>0.05). The CMSS scores in both groups were significantly lower than those after treatment (both P<0.05). The VAS scores at the follow-up of both groups had no statistical differences from those after treatment (both P>0.05). After treatment, the CMSS score in the herbal cake-partitioned moxibustion group was significantly lower than that in the mild moxibustion group (P<0.05). At the follow-up, there were no statistical differences in the CMSS score between the two groups (P>0.05). Conclusion: The herbal cake-partitioned moxibustion has the same therapeutic efficacy for dysmenorrhea as the mild moxibustion; the two moxibustion methods can significantly improve the concomitant symptoms of dysmenorrhea, and the herbal cake-partitioned moxibustion is little better.

Electronic moxibustion apparatus and traditional moxibustion in treating knee osteoarthritis: a randomized controlled trial / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of DZWJY-1 type electronic moxibustion apparatus and traditional moxibustion in treating knee osteoarthritis (KOA). Methods: A total of 76 eligible patients were randomized into an electronic moxibustion apparatus group and a traditional moxibustion group, with 38 cases in each group. The electronic moxibustion apparatus group was intervened by DZWJY-1 type electronic moxibustion apparatus, and the traditional moxibustion group received moxa stick moxibustion for treatment. Neixiyan (EX-LE 4), Dubi (ST 35), Xuehai (SP 10) and Liangqiu (ST 34) were selected for both groups and the treatment was conducted 3 times a week for a total of 12 times. The visual analog scale (VAS) and the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) scores were observed before treatment and after 6 and 12 sessions of treatment, respectively. Results: There were 4 dropout cases in the traditional moxibustion group. Therefore, this trial had 72 valid cases, including 38 cases in the electronic moxibustion apparatus group and 34 cases in the traditional moxibustion group, the differences in the baseline data between the two groups were statistically insignificant (P>0.05). After 6 and 12 sessions of treatment, the VAS scores decreased significantly with the increase of treatment sessions in both groups (all P<0.01), and the betweengroup differences were statistically insignificant at the same time points (both P>0.05). The pain intensity was evaluated using the weighted value of VAS score. The markedly effective rate was 47.4％ and the total effective rate was 89.5％ in the electronic moxibustion apparatus group, versus 50.0％ and 94.1％ in the traditional moxibustion group, and the betweengroup differences were statistically insignificant (both P>0.05). After 6 and 12 sessions of treatment, the total score and the component scores including pain, stiffness and difficulty moving in the WOMAC decreased significantly with the increase of treatment sessions in both groups (all P<0.01), and the between-group differences were statistically insignificant (all P>0.05). Conclusion: Electronic moxibustion apparatus and traditional moxibustion both are effective in reducing joint pain and improving joint function in KOA patients, and they are equivalent comparing the clinical efficacy.

Pharmacological actions of neferine in the modulation of human platelet function.

Neferine has long been recognized as a medicinal herbal ingredient with various physiological and pharmacological activities. Although previous studies have reported its antithrombotic effect, the underlying mechanisms have not been thoroughly investigated. Since platelets play a key role in thrombosis, we investigated the effects of neferine on human platelet function and the potential mechanisms. Platelet aggregation, adhesion and spreading were performed to investigate the effect of neferine on inhibition of platelet function. Flow cytometry was used to determine platelet alpha granule secretion and integrin IIb/IIIa activation, as detected by CD62P (P-selectin) expression, PAC-1 and fibrinogen binding. Western blotting was utilized to investigate the effect of neferine on intracellular signaling of activated platelet. We found that neferine significantly suppressed platelet aggregation and remarkably promoted the dissociation of platelet aggregates induced by collagen, thrombin, U46619, ADP and adrenaline in a dose-dependent manner. Flow cytometry analysis showed that neferine inhibited thrombin-induced platelet P-selectin expression, PAC-1 and fibrinogen binding. In addition, neferine reduced the adhesion of human platelets on coated collagen under both static and shearing condition at an arterial shear rate of 40 dyne/cm2. Neferine also inhibited the spreading of human platelets on immobilized fibrinogen. Western blot analysis showed that neferine inhibited PI3K activation, and decreased the levels of phosphorylation of Akt, GSK3ß and p38 MAPK in platelets. In summary, neferine has the potential to be an antiplatelet and antithrombotic agent by inhibiting the PI3K-Akt-GSK3ß/p38 MAPK signaling pathway.

Plasma 25-Hydroxyvitamin D Concentrations Are Inversely Associated with All-Cause Mortality among a Prospective Cohort of Chinese Adults Aged ≥80 Years.

BACKGROUND: High concentrations of plasma 25-hydroxyvitamin D [25(OH)D], a marker of circulating vitamin D, have been associated with a lower risk of mortality in epidemiologic studies of multiple populations, but the association for Chinese adults aged ≥80 y (oldest old) remains unclear. OBJECTIVE: We investigated the association between plasma [25(OH)D] concentration and all-cause mortality among Chinese adults aged ≥80 y. DESIGN: The present study is a prospective cohort study of 2185 Chinese older adults (median age: 93 y). Prospective all-cause mortality data were analyzed for survival in relation to plasma 25(OH)D using Cox proportional hazards regression models, with adjustments for potential sociodemographic and lifestyle confounders and biomarkers. The associations were measured with HR and 95% CIs. RESULTS: The median plasma 25(OH)D concentration was 34.4 nmol/L at baseline. Over the 5466 person-year follow-up period, 1100 deaths were identified. Men and women were analyzed together as no effect modification by sex was found. After adjusting for multiple potential confounders, the risk of all-cause mortality decreased as the plasma 25(OH)D concentration increased (P-trend <0.01). Compared with the lowest age-specific quartile of plasma 25(OH)D, the adjusted HRs for mortality for the second, third, and fourth age-specific quartiles were 0.72 (95% CI: 0.57, 0.90), 0.73 (95% CI: 0.58, 0.93), and 0.61 (95% CI: 0.47, 0.81), respectively. The observed associations were broadly consistent across age and other subgroups. Sensitivity analyses generated similar results after excluding participants who died within 2 y of follow-up or after further adjustment for ethnicity and chronic diseases. CONCLUSIONS: A higher plasma 25-hydroxyvitamin D concentration was associated with a reduced risk of all-cause mortality among Chinese adults aged ≥80 y. This observed inverse association warrants further investigation in randomized controlled trials testing vitamin D supplementation in this age group.

Signal pathways, diseases, and functions associated with the miR-19a/92a cluster and the use of berberine to modulate the expression of this cluster in multiple myeloma cells.

BACKGROUND: Berberine downregulated miR-19a/92a cluster expression in multiple myeloma (MM) cells. METHODS: The cell viability of MM cells after berberine treatment was measured by CCK8 assay. qRT-PCR assay validated miR-19a/92a expression in multiple myeloma cells. TAM database analyzed miR-19a/92a-associated disease. miREnvironment database revealed that effects of environmental factors on the miR-19a/92a cluster. By targeting the seed region in the miRNA, the role of t-anti-miR-19a/92a cluster was evaluated by cell proliferation, migration, and colony formation. RESULTS: Berberine inhibited the cell viability of MM cells and downregulated the expression of miR-19a/92a. Seven kinds of hematological malignancies are closely associated with miR-19a/92a expression. By targeting the seed region of the miRNA, t-anti-miR-19a/92a significantly inhibits multiple myeloma cell proliferation, migration, and colony formation. CONCLUSION: Our findings may exhibit that miR-19a/92a cluster is a therapeutic target for MM and provide new mechanistic insight into the anti-MM effects of certain compounds in traditional Chinese herbal medicines.

Observation on lower-reinforcing and upper-reducing acupuncture method for hyperplasia of mammary gland and its influence on estradiol and progesterone / 针灸推拿医学（英文版）

Objective:To observe the clinical effect of lower-reinforcing and upper-reducing acupuncture method for hyperplasia of mammary gland (HMG) and its influence on estradiol (E2) and progesterone (P).Methods:A randomized,single-blinded and controlled trial was conducted.A total of 124 cases conforming to the inclusion criteria were randomized by random number table into a treatment group and a control group,with 62 cases in each group.Patients in both groups received acupuncture therapy at the same acupoints,while patients in the treatment group received lower-reinforcing and upper-reducing method,and patients in the control group received even reinforcing-reducing manipulation.The treatment started around 10 d before menstruation and was conducted every other day.Patients received 5 treatments in each menstruation cycle for consecutive 3 cycles.The levels of E2,P and E2/P and clinical efficacy were measured before and after treatment.Results:After treatment,the breast lump size,pain intensity and concomitant symptoms score in both groups were substantially lower than those before treatment,showing statistical significances (all P＜0.01),and the improvement in the treatment group was higher than that in the control group,and the between-group comparisons showed statistical significances (all P＜0.01).After treatment,the overall effective rate was 91.9％ in the treatment group,higher than 72.6％ in the control group,and the between-group comparison showed a statistical significance (P＜0.01).After treatment,levels of E2,P and E2/P value showed no statistical significance when compared with those before treatment in the two groups (all P＞0.05).Conclusion:Lower-reinforcing and upper-reducing acupuncture method can effectively alleviate clinical symptoms and signs in HMG patients,and produce a better effect than even reinforcing-reducing manipulation.The majority of HMG patients' E2,P level and E2/P value were not beyond the normal ranges;therefore,acupuncture showed no substantial influence on E2 and P levels and E2/P value.

Integrative analysis of signaling pathways and diseases associated with the miR-106b/25 cluster and their function study in berberine-induced multiple myeloma cells.

Berberine (BBR), a traditional Chinese herbal medicine compound, has emerged as a novel class of anti-tumor agent. Our previous microRNA (miRNA) microarray demonstrated that miR-106b/25 was significantly down-regulated in BBR-treated multiple myeloma (MM) cells. Here, systematic integration showed that miR-106b/25 cluster is involved in multiple cancer-related signaling pathways and tumorigenesis. MiREnvironment database revealed that multiple environmental factors (drug, ionizing radiation, hypoxia) affected the miR-106b/25 cluster expression. By targeting the seed region in the miRNA, tiny anti-mir106b/25 cluster (t-anti-mir106b/25 cluster) significantly induced suppression in cell viability and colony formation. Western blot validated that t-anti-miR-106b/25 cluster effectively inhibited the expression of P38 MAPK and phospho-P38 MAPK in MM cells. These findings indicated the miR-106b/25 cluster functioned as oncogene and might provide a novel molecular insight into MM.

Antiplatelet activity of loureirin A by attenuating Akt phosphorylation: In vitro studies.

Loureirin A is a flavonoid extracted from Dragon׳s Blood that has been used to promote blood circulation and remove stasis in Chinese traditional medicine. However, the mechanisms of these effects are not fully understood. We explored the anti-platelet activity and underlying mechanism of loureirin A in vitro. Our results indicated that loureirin A negatively affected agonist-induced platelet aggregation such as collagen, collagen-related peptide (CRP), ADP and thrombin. Loureirin A inhibited collagen-induced platelet ATP secretion and thrombin-stimulated P-selectin expression in a dose-dependent manner. Platelet spreading on immobilized fibrinogen was significantly impaired in the presence of loureirin A. Immunoblotting analysis indicated that 100µM of loureirin A almost completely eliminated collagen-induced Akt phosphorylation at Ser473. Interestingly, a submaximal dose (50µM) of loureirin A had an additive inhibitory effect with the phosphoinositide 3-kinase (PI3K) inhibitor Ly294002 on collage-induced Akt phosphorylation in platelets. Taken together, loureirin A had an inhibitory effect on platelet activation, perhaps through an impairment of PI3K/Akt signaling.

Effect of short-term high-dose atorvastatin on systemic inflammatory response and myocardial ischemic injury in patients with unstable angina pectoris undergoing percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) could develop periprocedural myocardial infarction and inflammatory response and statins can modify inflammatory responses property. The aim of this study was to evaluate whether short-term high-dose atorvastatin therapy can reduce inflammatory response and myocardial ischemic injury elicited by PCI. METHODS: From March 2012 to May 2014, one hundred and sixty-five statin-naive patients with unstable angina referred for PCI at Department of Cardiology of the 306th Hospital, were enrolled and randomized to 7-day pretreatment with atorvastatin 80 mg/d as high dose group (HD group, n = 56) or 20 mg/d as normal dose group (ND group, n = 57) or an additional single high loading dose (80 mg) followed 6-day atorvastatin 20 mg/d as loading dose group (LD group, n = 52). Plasma C-reactive protein (CRP) and interleukin-6 (IL-6) levels were determined before intervention and at 5 minutes, 24 hours, 48 hours, 72 hours, and 7 days after intervention. Creatine kinase-myocardial isoenzyme (CK-MB) and cardiac troponin I (cTnI) were measured at baseline and then 24 hours following PCI. RESULTS: Plasma CRP and IL-6 levels increased from baseline after PCI in all groups. CRP reached a maximum at 48 hours and IL-6 level reached a maximum at 24 hours after PCI. Plasma CRP levels at 24 hours after PCI were significantly lower in the HD group ((9.14±3.02) mg/L) than in the LD group ((11.06±3.06) mg/L) and ND group ((12.36±3.08) mg/L, P < 0.01); this effect persisted for 72 hours. IL-6 levels at 24 hours and 48 hours showed a statistically significant decrease in the HD group ((16.19±5.39) ng/L and (14.26±4.12) ng/L, respectively)) than in the LD group ((19.26±6.34) ng/L and (16.03±4.08) ng/L, respectively, both P < 0.05) and ND group ((22.24±6.98) ng/L and (17.24±4.84) ng/L, respectively). IL-6 levels at 72 hours and 7 days showed no statistically significant difference among the study groups. Although PCI caused a significant increase in CK-MB and cTnI at 24 hours after the procedure in all groups, the elevated CK-MB and cTnI values were lower in the HD group ((4.71±4.34) ng/ml and (0.086±0.081) ng/ml, respectively) than in the ND group ((7.24±6.03) ng/ml and (0.138±0.103) ng/ml, respectively, both P < 0.01) and LD group ((6.80±5.53) ng/ml and (0.126±0.101) ng/ml, respectively, both P < 0.01). CONCLUSION: Short-term high-dose atorvastatin treatment before PCI significantly reduced systemic inflammatory response and myocardial ischemic injury elicited by PCI.

[Effect of sodium tanshinone II (A) sulfonate on Ang II -induced atrial fibroblast collagen synthesis and TGF-beta1 activation].

OBJECTIVE: To observe the effect of sodium tanshinone II (A) sulfonate (STS) on Ang II -induced atrial fibroblast collagen synthesis and TGF-beta1 activation. METHOD: Atrial fibroblasts of neonatal rats were cultured to determine the content of collagen protein. The original synthesis rate determined by the [3H]-proline incorporation method was taken as the index for myocardial fibrosis. The content of active TGF-beta1 and total TGF-beta1 in cell culture supernatants were tested and cultured by ELISA. The expression of thrombospondin-1 (TSP-1) was assessed by using Western blot. RESULT: Ang II could significantly increase the content of atrial fibroblast collagen and the collagen synthesis rate, the TSP-1 expression and the concentration of active TGF-beta1, without any obvious change in total TGF-beta1. After the STS treatment, all of the indexes, apart from total TGF-beta1, were obviously down-regulated. CONCLUSION: STS could decrease the secretion of Ang II -induced atrial fibroblast collagen and the synthesis rate. Its mechanism is related to the inhibition of TSP-1/TGF-beta1 pathway.

Neferine exerts its antithrombotic effect by inhibiting platelet aggregation and promoting dissociation of platelet aggregates.

INTRODUCTION: Neferine, a kind of isoquinoline alkaloid, extracted from the seed embryo of Nelumbo nucifera Gaertn, has long been recognized in traditional medicine as a medicinal plant with various usages. Neferine has many biological activities, including anti-hypertensive, anti-arrhythmic, negative inotropic effect and relaxation on vascular smooth muscle. Although previous studies have reported its antithrombotic effect, the mechanisms by which it exerts antithrombotic effect have not been thoroughly studied. METHOD: Washed mice platelets and mice platelet-rich-plasma (PRP) were used to investigate the effects of neferine on platelet aggregation, secretion induced by various agonists and dissociation of agonist-formed platelet aggregates. Bioflux plates coated with collagen were used to investigate the effect of neferine on platelet adhesion and thrombosis in vitro. With collagen-epinephrine-induced acute pulmonary thrombus formation mouse model, the effect of neferine on thrombosis in vivo was also examined. RESULTS: Neferine, significantly and dose-dependently, inhibited collagen-, thrombin-, U46619-induced platelet aggregation in mice washed platelets, or ADP-induced platelet aggregation in PRP. Neferine treatment decreased platelet dense granule secretion initiated by collagen, thrombin and U46619. Also, Neferine dramatically and dose-dependently promoted the dissociation of platelet aggregates pre-formed by various agonists including collagen, thrombin, U46619 or ADP. Neferine can significantly reduce the area of mice platelets adhesion to the collagen and inhibit thrombosis in vitro. In collagen-epinephrine-induced acute pulmonary thrombus mouse model, neferine, at 6 mg/kg, significantly attenuated thrombus formation. CONCLUSIONS: Neferine remarkably prevents thrombus formation by inhibiting platelet activation, adhesion and aggregation, as well as promoting disassembly of pre-formed platelet aggregates. The inhibitory effects of neferine on platelet activation might be relevant in cases involving aberrant platelet activation where neferine could be used as an anti-platelet and antithrombotic agent.

Randomized controlled study on proximal needling for sciatica / 中国针灸

<p><b>OBJECTIVE</b>To compare the effect of proximal needling and routine acupuncture for sciatica.</p><p><b>METHODS</b>Sixty patients with sciatica were randomly divided into a proximal needling group and a routine acupuncture group, 30 cases in each group. The proximal needling group was treated by proximal needling at Huantiao (GB 30). The routine acupuncture group was treated by acupuncture at Huantiao (GB 30), Yinmen (BL 37), Weizhong (BL 40), Yanglingquan (GB 34) etc. with routine acupuncture method. The Numerical Pain Rating Scales (NPRS) the Japanese Orthopaedic Association Scores (JOA) were all observed before, after treatment and in following up.</p><p><b>RESULTS</b>The total effective rates were 100.0% (30/30) in both groups, with no significant difference between the two groups (P > 0.05) in 3 month follow up. After 5 treatments, the total improvement rate of 100.0% (30/30) in the proximal needling group was super to that of 80.0% (24/30) in the routine acupuncture group. The NPRS and JOA scores were all improved significantly after 5 treatment and in following up compared with those before treatment in two groups (all P < 0.01). After treatments, the improvement of the NPRS and JOA scores in the proximal needling group was greater than those in the routine acupuncture group (both P < 0.05).</p><p><b>CONCLUSION</b>The proximal needling treatment has rapid and obvious therapeutic effect and analgesia on sciatica.</p>

[Investigation and analysis of plasma trace elements of oldest elderly in longevity areas in China].

OBJECTIVE: To investigate the levels and differences of plasma selenium, manganese, iron, copper, zinc among oldest elderly in longevity areas in China. METHODS: 446 oldest elderly including 208 centenarians, 238 aged 90 and over, who lived in Xiayi county of Henan province (110 persons), Zhongxiang city of Hubei province (111 persons), Mayang county of Hunan province (60 persons), Sanshui district of Guangdong province (113 persons), Yongfu county of Guangxi Zhuang autonomous region (52 persons) in China, were selected. The contents of plasma selenium, manganese, iron, copper, zinc were detected and compared among these elderly who were classified into different genders, different regions and different age groups. RESULTS: In oldest elderly, the median (inter-quartile range) of content of plasma selenium was 1.44 (0.91) micromol/L, content of manganese was 0.54 (0.94) micromol/L, content of iron was 69.17 (102.85) micromol/L, content of copper was 20.19 (8.73) micromol/L, content of zinc was 31.66 (32.51) micromol/L. Contents of plasma selenium of oldest elderly in Xiayi, Zhongxiang, Mayang, Sanshui, Yongfu region were 1.46 (0.66), 1.30 (0.80), 1.06 (0.51), 2.39 (1.53) and 1.35(0.55) micromol/L; contents of plasma manganese were 0.56 (0.51), 1.40 (1.11), 0.35 (0.71), 0.44 (0.55) and 0.15 (0.21) micromol/L; contents of plasma iron were 86.77 (86.87), 141.42 (101.83), 38.88 (36.28), 31.38 (46.19) and 79.64 (75.34) micromol/L; contents of plasma copper were 22.16 (8.11), 19.46 (9.26), 21.36 (12.38), 18.12 (6.74) and 21.47 (7.85) micromol/L; contents of plasma zinc were 36.85 (26.18), 36.59 (35.94), 39.98 (56.91), 25.05 (24.92) and 16.74 (16.81) micromol/L. Contents of plasma trace elements among oldest elderly in different longevity areas were significantly different (F values were 29.76, 38.75, 47.18, 11.51 and 13.47, P values were all less than 0.05). Contents of plasma trace elements in different gender groups (contents of plasma selenium were 1.38 (0.83) micromol/L in male and 1.45 (0.91) micromol/L in female; contents of plasma manganese were 0.52 (0.95) and 0.54 (0.91) micromol/L; contents of plasma iron were 69.23 (104.06) and 69.11 (101.05) micromol/L; contents of plasma copper were 20.28 (8.72) and 20.06 (8.76) micromol/L; contents of plasma zinc were 28.39 (32.58) and 31.85 (34.26) micromol/L) were not significantly different (t(Se) = -1.82, P = 0.07; t(Mn) = 0.64, P = 0.52; t(Fe) = 0.65, P = 0.52; t(Cu) = -1.90, P = 0.06; t(Zn) = -0.96, P = 0.34). The contents of plasma selenium, iron, copper in centenarians were higher than those aged 90 and over (contents of plasma selenium were 1.63 (0.94) micromol/L and 1.30 (0.82) micromol/L, contents of plasma iron were 112.63 (119.78) and 60.13 (58.43) micromol/L, contents of plasma copper were 21.07 (9.03) and 18.81 (8.86) micromol/L, F value were 41.99, 27.32, 24.45, P values were less than 0.01). Content of plasma manganese in centenarians was lower than those aged 90 and over (0.44 (0.76) and 0.64 (0.93) micromol/L, F = 10.76, P < 0.01). No significant differences were detected in plasma zinc between concentration and those aged 90 and over (31.78 (34.06) and 31.11 (33.85) micromol/L; F = 1.32, P = 0.25). CONCLUSION: The concentrations of plasma selenium, manganese, iron, copper and zinc were high in oldest elderly in the longevity areas. The contents of plasma selenium, iron, copper increased with age.