Clinical observation of Qiliqiangxin capsule combined with recombinant human brain natriuretic peptide in patients with acute heart failure / 中华内科杂志

Objective: To observe the clinical effect of Qiliqiangxin capsule combined with recombinant human brain natriuretic peptide in acute left heart failure patients 7 days after onset as well as the effects of plasma MDA and ET-1. Methods: In total, 240 hospitalized patients with acute left heart failure from October 2017 to May 2021 were selected from the Department of Emergency and Critical Care Center of Beijing Anzhen Hospital, Capital Medical University and the Department of Cardiology of the Jilin Provincial People's Hospital. They were randomly divided into routine treatment group and combined treatment group, with 120 cases in each group. The routine treatment group was treated with vasodilation, diuresis, cardiotonic and recombinant human brain natriuretic peptide. The combined treatment group was treated with Qiliqiangxin capsules based on the routine treatment group. One week later, the changes in clinical efficacy, ejection fraction, left ventricular commoid diameter, and plasma BNP, MDA, and ET-1 were compared between the two groups before and after treatment. SPSS 11.5 statistical software was used. The measurement data was expressed in x¯±s, the independent sample t-test was used for comparison between groups, and the paired t-test was used for comparison before and after treatment within groups. Counting data was expressed as case (%), and the rank sum test was used for inter-group comparison. Result: In terms of clinical efficacy, the total effective rate of the combined treatment group was significantly higher than that of the conventional treatment group, and the difference was statistically significant (P<0.05). Compared with the routine treatment group, the left ventricular ejection fraction in the combined treatment group was significantly increased (P<0.05). The levels of plasma BNP, MDA and ET-1 were significantly decreased (P<0.05). Conclusion: Qiliqiangxin capsule combined with rhBNP treatment can effectively improve the clinical symptoms of acute heart failure, as well as reduce the lipid peroxidation product MDA content and endothetin ET-1 level in blood. The clinical application value of the Qiliqiangxin capsule needs to be further confirmed by further trials.

Jinlida granules ameliorate the high-fat-diet induced liver injury in mice by antagonising hepatocytes pyroptosis.

CONTEXT: Jinlida (JLD) as a traditional Chinese medicine formula has been used to treat type 2 diabetes mellitus (T2DM) and studies have shown its anti-obesity effect. OBJECTIVE: To investigate the therapeutic effects of JLD in a mouse model of non-alcoholic fatty liver (NAFL). MATERIALS AND METHODS: C57BL/6J mice were divided into three groups and fed a low-diet diet (LFD), high-fat diet (HFD), or HFD + JLD (3.8 g/kg) for 16 weeks, respectively. The free fatty acids-induced lipotoxicity in HepG2 cells were used to evaluate the anti-pyroptotic effects of JLD. The pharmacological effects of JLD on NAFL were investigated by pathological examination, intraperitoneal glucose and insulin tolerance tests, western blotting, and quantitative real-time PCR. RESULTS: In vivo studies showed that JLD ameliorated HFD-induced liver injury, significantly decreased body weight and enhanced insulin sensitivity and improved glucose tolerance. Furthermore, JLD suppressed both the mRNA expression of caspase-1 (1.58 vs. 2.90), IL-1ß (0.93 vs. 3.44) and IL-18 (1.34 vs. 1.60) and protein expression of NLRP3 (2.04 vs. 5.71), pro-caspase-1 (2.68 vs. 4.92) and IL-1ß (1.61 vs. 2.60). In vitro, JLD inhibited the formation of lipid droplets induced by 2 mM FFA (IC50 = 2.727 mM), reduced the protein expression of NLRP3 (0.74 vs. 2.27), caspase-1 (0.57 vs. 2.68), p20 (1.67 vs. 3.33), and IL-1ß (1.44 vs. 2.41), and lowered the ratio of p-IKB-α/IKB-α (0.47 vs. 2.19). CONCLUSION: JLD has a protective effect against NAFLD, which may be related to its anti-pyroptosis, suggesting that JLD has the potential as a novel agent in the treatment of NAFLD.

Taraxasterol mitigates Con A-induced hepatitis in mice by suppressing interleukin-2 expression and its signaling in T lymphocytes.

Discovery of anti-inflammatory drugs that can suppress T lymphocyte activation and proliferation by inhibiting TCR/CD3 and IL-2/IL-2R signaling is still needed in clinic, though rapamycin and other related reagents have made great success. Taraxasterol (TAS) is an active ingredient of dandelion, an anti-inflammatory medicinal herb with low in vivo toxicity that has long been used in China. Yet the action mechanism of TAS on lymphocytes remains elusive. The anti-inflammatory effects of TAS were evaluated in C57BL/6 mouse primary lymphocytes stimulated with concanavalin A (Con A) in vitro and in mouse model of Con A-induced acute hepatitis in vivo. Our results showed that TAS significantly suppressed Con A-induced acute hepatitis in a mouse model, reducing the hepatic necrosis areas, the release of aminotransferases, and the production of IL-2 and other inflammatory cytokines. Supporting this, in vitro study also showed that TAS reduced the production of IL-2 and the expression of IL-2 receptor subunit α (CD25) upon the stimulation of Con A, which was likely mediated by suppressing NF-κB activation. The downstream pathways of IL-2/IL-2R signaling, including the activation of PI3K/PDK1/mTOR, STAT3 and STAT5, were also suppressed by TAS. Consistently, Con A-induced T cell proliferation was also inhibited by TAS in vitro. Our data indicate that TAS can suppress both T lymphocyte activation and cell proliferation by down-regulating IL-2 expression and its signaling pathway thereby ameliorating Con A-induced acute hepatitis, highlighting TAS as a potential drug candidate for treating inflammatory diseases including autoimmune hepatitis.

Inhibition of NLRP3 Inflammasome Activation and Pyroptosis in Macrophages by Taraxasterol Is Associated With Its Regulation on mTOR Signaling.

Taraxasterol (TAS) is an active ingredient of Dandelion (Taraxacum mongolicum Hand. -Mazz.), a medicinal plant that has long been used in China for treatment of inflammatory disorders. But the underlying mechanism for its therapeutic effects on inflammatory disorders is not completely clear. Inflammasome activation is a critical step of innate immune response to infection and aseptic inflammation. Among the various types of inflammasome sensors that has been reported, NLR family pyrin domain containing 3 (NLRP3) is implicated in various inflammatory diseases and therefore has been most extensively studied. In this study, we aimed to explore whether TAS could influence NLPR3 inflammasome activation in macrophages. The results showed that TAS dose-dependently suppressed the activation of caspase-1 in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin treatment, resulting in reduced mature interleukin-1ß (IL-1ß) release and gasdermin D (GSDMD) cleavage. TAS greatly reduced ASC speck formation upon the stimulation of nigericin or extracellular ATP. Consistent with reduced cleavage of GSDMD, nigericin-induced pyroptosis was alleviated by TAS. Interestingly, TAS time-dependently suppressed the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and mTORC2 signaling induced by LPS priming. Like TAS, both INK-128 (inhibiting both mTORC1 and mTORC2) and rapamycin (inhibiting mTORC1 only) also inhibited NLRP3 inflammasome activation, though their effects on mTOR signaling were different. Moreover, TAS treatment alleviated mitochondrial damage by nigericin and improved mouse survival from bacterial infection, accompanied by reduced IL-1ß levels in vivo. Collectively, by inhibiting the NLRP3 inflammasome activation, TAS displayed anti-inflammatory effects likely through regulation of the mTOR signaling in macrophages, highlighting a potential action mechanism for the anti-inflammatory activity of Dandelion in treating inflammation-related disorders, which warrants further clinical investigation.

Effects of Niaoduqing Particles () on Delaying Progression of Renal Dysfunction: A Post-trial, Open-Label, Follow-up Study / 中国结合医学杂志

OBJECTIVE@#To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction.@*METHODS@#Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period.@*RESULTS@#After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min•1.73 m, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min•1.73 m, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min•1.73 m per year.@*CONCLUSION@#Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).

Neuroprotective Effects of Electroacupuncture Preventive Treatment in Senescence-Accelerated Mouse Prone 8 Mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the preventive treatment effects of electroacupuncture (EA) on cognitive changes and brain damage in senescence-accelerated mouse prone 8 (SAMP8) mice.</p><p><b>METHODS</b>The 5-month-old male SAMP8 and age-matched homologous normal aging mice (SAMR1) were adopted in this study. EA stimulation at Baihui (GV 20) and Yintang (EX-HN 3) was performed every other day for 12 weeks, 4 weeks as a course. Morris water maze test and Nissl-stained with cresyl violet were used for cognitive impairments evaluation and brain morphometric analysis. Amyloid-β (A β) expression in hippocampus and parietal cortex was detected by immunohistochemistry, and apoptosis was observed by TUNEL staining.</p><p><b>RESULTS</b>After 3 courses of EA preventive treatment, the escape latencies of 8-month-old SAMP8 mice in EA group were significantly shortened than those of un-pretreated SAMP8 mice. Compared with SAMR1 mice, extensive neuronal changes were visualized in the CA1 area of hippocampus in SAMP8 mice, while these pathological changes and attenuate cell loss in hippocampal CA1 area of SAMP8 mice markedly reduced after EA preventive treatment. Furthermore, A β expression in hippocampus and parietal cortex of SAMP8 mice decreased significantly after EA treatment, and neuronal apoptosis decreased as well.</p><p><b>CONCLUSION</b>EA preventive treatment at GV 20 and EX-HN 3 might improve cognitive deficits and neuropathological changes in SAMP8 mice, which might be, at least in part, due to the effects of reducing brain neuronal damage, decreasing neuronal apoptosis and inhibiting A β-containing aggregates.</p>

Research of the Consistency between Pathology and the Single and Combined Diagnosis of Negative Breast Cancer by Ultrasonography and Mammography / 医学研究杂志

Objective To study the consistency between pathology and the single and combined diagnosis of negative breast cancer by ultrasonography and mammography.Methods 90 clinical case data of patients with palpable negative breast tumors and mammography revealed small calcifications were retrospective analyzed.All patients were received the high frequency ultrasound.The value of two methods and combined diagnosis in the diagnosis of breast cancer with palpation negative were compared,which the pathological biopsy was the gold standard.Results The pathological showed that there were 58 cases of benign tumors,32 cases of malignant tumors,10 cases of stage 0,18 cases of stage Ⅰ,4 cases of stage Ⅱ.The high frequency ultrasonography was consistent with pathological(Kappa =0.641).The AUC of diagnosiing the breast cancer was 0.775.The molybdenum target radiography was consistent with pathological (Kappa =0.725),and the AUC was 0.830.The high frequency ultrasonography combined with molybdenum target radiography was highly consistent with pathological(Kappa =0.879),and the AUC was 0.934.The accuracy of combined diagnosis was higher than that of high frequency ultrasound (P ＜ 0.05) and molybdenum target radiography(P ＞ 0.05).Conclusion The high frequency ultrasonography and molybdenum target radiography have advantages in the diagnosis of palpable negative breast cancer.The joint diagnosis helps to achieve complementary strengths,has high consistency with pathology,and help to improve the diagnostic accuracy.

Discovery and Modification of in Vivo Active Nrf2 Activators with 1,2,4-Oxadiazole Core: Hits Identification and Structure-Activity Relationship Study.

Induction of phase II antioxidant enzymes by activation of Nrf2/ARE pathway has been recognized as a promising strategy for the regulation of oxidative stress-related diseases. Herein we report our effort on the discovery and optimization of Nrf2 activators with 1,2,4-oxadiazole core. Screening of an in-house collection containing 7500 compounds by ARE-luciferase reporter assay revealed a moderate Nrf2 activator, 1. Aimed at obtaining more derivatives efficiently, molecular similarity search by the combination of 2D fingerprint-based and 3D shape-based search was applied to virtually screening the Chemdiv collection. Three derivatives with the same core were identified to have better inductivity of Nrf2 than 1. The best hit 4 was selected as starting point for structurally optimization, leading to a much more potent derivative 32. It in vitro upregulated gene and protein level of Nrf2 as well as its downstream markers such as NQO1, GCLM, and HO-1. It remarkably suppressed inflammation in the in vivo LPS-challenged mouse model. Our results provide a new chemotype as Nrf2-ARE activators which deserve further optimization with the aim to obtain active anti-inflammatory agents through Nrf2-ARE pathway.

Relationship between selection of Pinus massoniana families and Folium Pini / 中国中药杂志

Based on variation of Pinus massoniana families, heritablility and correlation analysis, the contents of shikimic acid and procyanidine (heritability 0.90, 0.70), dry weight of single branch (heritability 0.60) and and leaf length (heritability 0.46) were screened out as quality, yield and harvest cost traits of Folium Pini, respectively. For the different medicinal application of Folium Pini, varied methods were chosen to estimate weight and construct index equation. Weight adjustment based.on equal emphasis were used as economic weight determining method to select the best families, and the index (accuracy 0. 936 4 and heritability 0. 881 6) obtained was a little better than that obtained by equal emphasis, and much better than that by restricted index. The superior families selected with adjustment weight and equal emphasis were No. 46, 43 and 28. Partial regression were used as economic weight determining method to select the best families,and the index obtained had the highest accuracy (0.941 5) , index heritability (0. 889 9) and the genetic gain of shikimic acid content. The superior families selected with this method were No. 46, 27 and 47. No. 46 was the best families with maximal economic benefit. Our study indicated that suitable method for estimate weight and construct index equation can be applied for better accuracy of superior families selection of P. massoniana.

[Applications and prospects of on-line near infrared spectroscopy technology in manufacturing of Chinese materia medica].

The quality of Chinese materia medica (CMM) is affected by every process in CMM manufacturing. According to multi-unit complex features in the production of CMM, on-line near infrared spectroscopy (NIR) is used as an evaluating technology with its rapid, non-destructive and non-pollution etc. advantages. With the research in institutions, the on-line NIR applied in process analysis and control of CMM was described systematically, and the on-line NIR platform building was used as an example to clarify the feasibility of on-line NIR technology in CMM manufacturing process. Then, from the point of application by pharmaceutical companies, the current on-line NIR research on CMM and its production in pharmaceutical companies was relatively comprehensively summarized. Meanwhile, the types of CMM productions were classified in accordance with two formulations (liquid and solid dosage formulations). The different production processes (extraction, concentration and alcohol precipitation, etc. ) were used as liquid formulation diacritical points; the different types (tablets, capsules and plasters, etc.) were used as solid dosage formulation diacritical points, and the reliability of on-line NIR used in the whole process in CMM production was proved in according to the summary of literatures in recent 10 years, which could support the modernization of CMM production.

Clinical research on fire filiform needle combined with mild moxibustion for postherpetic neuralgia / 中国针灸

<p><b>OBJECTIVE</b>To compare efficacy differences between fire filiform needle combined with mild moxibustion and gabapentin combined with sham acupuncture for postherpetic neuralgia (PHN).</p><p><b>METHODS</b>One hundred cases of PHN were randomly divided into a needle group and a medicine group, 50 cases in each one. In the needle group, pricking method of fire filiform needle was given at the Ashi points, and then mild moxibustion was applied for 15 min. In the medicine group, the oral administration of gabapentin capsule and sham acupuncture at non-acupoints in the distal end of lesions were applied. The treatment was required for 21 days in both groups. The visual analogue score (VAS) was recorded before treatment and on the 1st day, 2nd day, 3rd day, 6th day, 9th day and 12th day of treatment. The most severity of pain within last 24 h, preset severity of pain, immediate analgesia effect and starting time of pain relief were observed, also the efficacy was assessed and improvement of symptoms was observed in the follow-up visit.</p><p><b>RESULTS</b>The total effective rate was 94.0% (47/50) in the fire filiform needle group, which was superior to 86.0% (43/50) in the medicine group (P < 0.05). Compared with medicine group, the VAS of the most severity of pain within last 24 h was obviously reduced after the 2nd treatment in the fire filiform needle group while that of present severity of pain was relieved after the 1st treatment (both P < 0.05). The immediate analgesia effect in the fire filiform needle group was obviously superior to that in the medicine group in the first three times of treatment (all P < 0.05). The average time of pain relief was (3.91 +/- 0.82) days in the fire filiform needle group, which was significantly earlier to (6.53 +/- 1.13) days in the medicine group (P < 0.05). 26 cases were cured in the fire filiform needle group in the follow-up visit, which was superior to 2 cases in the medicine group (P < 0.05). The improvement of VAS, pain range and sleep quality in the needle group were also superior to those in the medicine group (all P < 0.05). The direct medical cost in the fire filiform needle group was (232.32 +/- 48.108) yuan, which was significantly lower than (466.00 +/- 41.09) yuan in the medicine group (P < 0.05). There was only one case of adverse effect in the medicine group during the treatment.</p><p><b>CONCLUSION</b>The fire filiform needle combined with mild moxibustion could obviously relieve the pain in PHN patients, which has superior immediate analgesia effect and pain relieving time compared with gabapentin, which also has less adverse effects and cheap cost.</p>

Study on immunological pathogenesis of 59 patients with multiple sclerosis of different TCM syndrome types / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the immunological pathogenesis of multiple sclerosis (MS) patients of different TCM syndrome types.</p><p><b>METHODS</b>Fifty-nine MS patients were assigned to two types by syndrome typing according to their clinical manifestations, the Gan-Shen yin-deficiency (GSYD, 40 cases) type and the both yin-yang deficiency (YYD, 19 cases) type. Difference of patients' age of first attack, times of relapsing, duration of disease, MRI finding and evoked potential between the two groups were compared. The immunology indexes were also compared in part of the patients (26 cases in GSYD type and 12 cases in YYD type).</p><p><b>RESULTS</b>The age of first attack was later (P < 0.01), level of myelin basic protein in cerebrospinal fluid was higher (P < 0.05), in the YYD type than those in the GSYD type. Besides, the relapsing time in GSYD type, and the blood-brain barrier index and level of myelin basic protein in YYD type showed an ascending trend (P = 0.056, 0.074, 0.093, respectively).</p><p><b>CONCLUSION</b>Immunological difference exists between the MS patients of GSYD type and those of YYD type.</p>

Effect of acupuncture serum on the number of osteclast cultured in vitro / 中国针灸

<p><b>OBJECTIVE</b>To observe effects of acupuncture serum of ovariectomized rats on the number of in vitro cultural osteoclast of newborn rats.</p><p><b>METHODS</b>Forty 12-month-old SD female rats were randomly divided into 4 groups: sham-operation control group, ovariectomized (model) group, acupuncture prevention group and acupuncture treatment group. Osteoclasts isolated from long bone of the newborn SD rat were cultured on 24-well culture plates with DMEM containing 10% the test serum. Forty-eight hours later, the osteoclasts were stained with tartrate resistant acid phosphatase (TRAP) and the number of TRAP-positive multinucleated cells were counted.</p><p><b>RESULTS</b>The number of TRAP-positive multinucleated cells in the model group significantly increased as compared with the sham-operation control group (P < 0.01), and in the acupuncture prevention group and the acupuncture treatment group significantly declined compared with the model group (P < 0.05).</p><p><b>CONCLUSION</b>Acupuncture serum can equally reduce the number of osteoclasts in the two group.</p>

Effects of ZuoGuiWan and YouGuiWan on lymphocyte subsets and NK cells in peripheral blood of EAE rats / 中华中医药杂志

Objective: To observe the effect of ZuoGuiWan and YouGuiWan on induced experimental autoimmune encephalomyelitis(EAE) in Lewis rats,compare the therapeutic effect between ZuoGuiWan and YouGuiWan,and explore the underlying immunoregulatory mechanism between warming-yang and nourishing-yin therapy.Methods : 120 male Lewis rats were bred at Capital Medical University under specifi c pathogen-free conditions.24 rats were selected as normal group before immunization.The other rats were randomly devided into 4 groups after immunization,including EAE group,prednisone group,ZuoGuiWan group and YouGuiWan group.Rats of normal group were injected with normal sodium in the hind feet pad on both sides,the other rats were injected with the antigen consisted of myelin basic protein(MBP) and complete Freund’s adjuvant(CFA) to induce EAE.Rats of normal group and EAE group were administered with normal sodium after immunization,rats of prednisone group with prednisone(5mg/kg),rats of ZuoGuiWan group with ZuoGuiWan(2g/kg),rats of YouGuiWan group with YouGuiWan(3g/kg).On the day 15 and 27 after immunization,the peripheral blood was collected,lymphocyte subgroups and NK cells were detected by ? ow cytometer.Results: On day 15 after immunization: In peripheral blood,the number of CD4+lymphocyte in ZuoGuiWan group was signifi cantly higher(P