Shikonin suppresses rheumatoid arthritis by inducing apoptosis and autophagy via modulation of the AMPK/mTOR/ULK-1 signaling pathway.

BACKGROUND: The overproliferation of fibroblast-like synoviocytes (FLS) contributes to synovial hyperplasia, a pivotal pathological feature of rheumatoid arthritis (RA). Shikonin (SKN), the active compound from Lithospermum erythrorhizon, exerts anti-RA effects by diverse means. However, further research is needed to confirm SKN's in vitro and in vivo anti-proliferative functions and reveal the underlying specific molecular mechanisms. PURPOSE: This study revealed SKN's anti-proliferative effects by inducing both apoptosis and autophagic cell death in RA FLS and adjuvant-induced arthritis (AIA) rat synovium, with involvement of regulating the AMPK/mTOR/ULK-1 pathway. METHODS: SKN's influences on RA FLS were assessed for proliferation, apoptosis, and autophagy with immunofluorescence staining (Ki67, LC3B, P62), EdU incorporation assay, staining assays of Hoechst, Annexin V-FITC/PI, and JC-1, transmission electron microscopy, mCherry-GFP-LC3B puncta assay, and western blot. In AIA rats, SKN's anti-arthritic effects were assessed, and its impacts on synovial proliferation, apoptosis, and autophagy were studied using Ki67 immunohistochemistry, TUNEL, and western blot. The involvement of AMPK/mTOR/ULK-1 pathway was examined via western blot. RESULTS: SKN suppressed RA FLS proliferation with reduced cell viability and decreased Ki67-positive and EdU-positive cells. SKN promoted RA FLS apoptosis, as evidenced by apoptotic nuclear fragmentation, increased Annexin V-FITC/PI-stained cells, reduced mitochondrial potential, elevated Bax/Bcl-2 ratio, and increased cleaved-caspase 3 and cleaved-PARP protein levels. SKN also enhanced RA FLS autophagy, featuring increased LC3B, reduced P62, autophagosome formation, and activated autophagic flux. Autophagy inhibition by 3-MA attenuated SKN's anti-proliferative roles, implying that SKN-induced autophagy contributes to cell death. In vivo, SKN mitigated the severity of rat AIA while also reducing Ki67 expression, inducing apoptosis, and enhancing autophagy within AIA rat synovium. Mechanistically, SKN modulated the AMPK/mTOR/ULK-1 pathway in RA FLS and AIA rat synovium, as shown by elevated P-AMPK and P-ULK-1 expression and decreased P-mTOR expression. This regulation was supported by the reversal of SKN's in vitro and in vivo effects upon co-administration with the AMPK inhibitor compound C. CONCLUSION: SKN exerted in vitro and in vivo anti-proliferative properties by inducing apoptosis and autophagic cell death via modulating the AMPK/mTOR/ULK-1 pathway. Our study revealed novel molecular mechanisms underlying SKN's anti-RA effects.

Selenium-SelK-GPX4 axis protects nucleus pulposus cells against mechanical overloading-induced ferroptosis and attenuates senescence of intervertebral disc.

Intervertebral disc degeneration (IVDD) is one of the most prevalent spinal degenerative disorders and imposes places heavy medical and economic burdens on individuals and society. Mechanical overloading applied to the intervertebral disc (IVD) has been widely recognized as an important cause of IVDD. Mechanical overloading-induced chondrocyte ferroptosis was reported, but the potential association between ferroptosis and mechanical overloading remains to be illustrated in nucleus pulposus (NP) cells. In this study, we discovered that excessive mechanical loading induced ferroptosis and endoplasmic reticulum (ER) stress, which were detected by mitochondria and associated markers, by increasing the intracellular free Ca2+ level through the Piezo1 ion channel localized on the plasma membrane and ER membrane in NP cells. Besides, we proposed that intracellular free Ca2+ level elevation and the activation of ER stress are positive feedback processes that promote each other, consistent with the results that the level of ER stress in coccygeal discs of aged Piezo1-CKO mice were significantly lower than that of aged WT mice. Then, we confirmed that selenium supplementation decreased intracellular free Ca2+ level by mitigating ER stress through upregulating Selenoprotein K (SelK) expression. Besides, ferroptosis caused by the impaired production and function of Glutathione peroxidase 4 (GPX4) due to mechanical overloading-induced calcium overload could be improved by selenium supplementation through Se-GPX4 axis and Se-SelK axis in vivo and in vitro, eventually presenting the stabilization of the extracellular matrix (ECM). Our findings reveal the important role of ferroptosis in mechanical overloading-induced IVDD, and selenium supplementation promotes significance to attenuate ferroptosis and thus alleviates IVDD, which might provide insights into potential therapeutic interventions for IVDD.

Adjuvant therapy following curative treatments for hepatocellular carcinoma: current dilemmas and prospects.

Curative surgical treatments, mainly liver resection, are still one of the optimal options for patients with early-, mid-, and even progression-stage hepatocellular carcinoma (HCC). However, the recurrence rate within 5 years after surgery is as high as 70%, especially in patients with high risk factors for recurrence, most of whom experience early recurrence within 2 years. Effective adjuvant therapy may improve prognosis, previous studies found that adjuvant transarterial chemoembolization, antiviral, and traditional Chinese medicine et al. were helpful in preventing HCC recurrence. Nevertheless, due to controversial results or lack of high-level evidence, there is no standardized postoperative management protocol worldwide at present. Continued exploration of effective postoperative adjuvant treatments to improve surgical prognosis is necessary.

Photothermal-accelerated urease-powered human serum albumin nanomotor for rapid and efficient photothermal and photodynamic cancer combination therapy.

Nanomotors, as a new type of micro-device, show good performance in terms of rapid transportation and deep penetration through their autonomous motion. However, their ability to efficiently break physiological barriers still remains a great challenge. Herein, we first developed a thermal-accelerated urease driven human serum albumin (HSA) nanomotor based on photothermal intervention (PTI) to achieve chemotherapy drugfree-phototherapy. The HANM@FI (HSA-AuNR@FA@Ur@ICG) is composed of a main body of biocompatible HSA, modified by gold nanorods (AuNR) and loaded with functional molecules of folic acid (FA) and indocyanine green (ICG). It promotes its own motion by breaking down urea to produce carbon dioxide and ammonia. In particular, the nanomotor is conveniently operated via near-infrared combined photothermal therapy (PTT)/ photodynamic therapy (PDT) to achieve an accelerated De value from 0.73 µm2s-1 to 1.01µm2s-1, and ideal tumor ablation at the same time. In contrast to customary urease-driven nanodrug-stacked engine, this HANM@FI has both targeting and imaging-guided capabilities, and finally achieves superior anti-tumor effects without chemotherapy drugs, through a "two-in-one" (motor mobility plus unique phototherapy in chemotherapy-drugfree phototherapy) strategy. This PTI effect with urease-driven nanomotors may offer further possibilities for future clinical applications of nanomedicines by enabling deep penetration and a subsequent chemotherapy-drugfree combination therapy strategy.

Tao-Hong-Si-Wu decoction improves depressive symptoms in model rats via amelioration of BDNF-CREB-arginase I axis disorders.

CONTEXT: The traditional Chinese medicine formula Tao-Hong-Si-Wu decoction (TSD), used for treating ischaemic stroke, has the potential to treat depressive disorder (DD). OBJECTIVE: To explore the effective targets of TSD on DD animal models. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were modelled by inducing chronic unpredictable mild stress (CUMS) during 35 days and treated with three dosages of TSD (2.5, 5 and 10 g/kg) or fluoxetine (10 mg/kg) by oral gavage for 14 days. Bodyweight measurements and behavioural tests were performed to observe the effect of TSD on the CUMS animals. A gas chromatography coupled with mass spectrometry (GC-MS)-based metabolomic analysis was conducted to reveal the metabolic characteristics related to the curative effect of TSD. Levels of the proteins associated with the feature metabolites were analysed. RESULTS: Reduced immobile duration and crossed squares in the behavioural tests were raised by 48.6% and 32.9%, on average, respectively, by TSD treatment (ED50=3.2 g/kg). Antidepressant effects of TSD were associated with 13 decreased metabolites and the restorations of ornithine and urea in the serum. TSD (5 g/kg) raised serum serotonin by 54.1 mg/dL but suppressed arginase I (Arg I) by 47.8 mg/dL in the CUMS rats. Proteins on the brain-derived neurotrophic factor (BDNF)-cAMP response element-binding protein (CREB) axis that modulate the inhibition of Arg I were suppressed in the CUMS rats but reversed by the TSD intervention. DISCUSSION AND CONCLUSIONS: TSD improves depression-like symptoms in CUMS rats. Further study will focus on the antidepressant-like effects of effective compounds contained in TSD.

Osmundacetone modulates mitochondrial metabolism in non-small cell lung cancer cells by hijacking the glutamine/glutamate/α-KG metabolic axis.

BACKGROUND: Osmundacetone (OSC) is a bioactive phenolic compound isolated from Phellinus igniarius and that was shown to exert cytotoxic effects on cancer cells in our previous work. The antiproliferative impact of OSC on non-small cell lung cancer (NSCLC) and the underlying mechanisms, however, have not been studied. PURPOSE: This study aimed to explore the antiproliferative effect of OSC on NSCLC cells and the mechanisms involved. METHODS: Cell viability, colony formation and cell cycle distribution were measured following exposure to OSC in vitro. The anticancer activity of OSC was also examined using a xenograft growth assay in vivo. Furthermore, serum metabolomics analysis by GC-MS was done to detect alterations in the metabolic profile. Next, expression of GLS1 and GLUD1, the key enzymes in glutamine metabolism, was evaluated using RT-PCR and western blot. α-KG and NADH metabolites were assessed by ELISA. Mitochondrial functions and morphology were evaluated using the JC-1 probe and transmission electron microscopy, respectively. The ATP production rate in mitochondria of cells with OSC treatment was determined using a Seahorse XFe24 Analyzer. RESULTS: OSC selectively reduced the proliferation of A549 and H460 cells. OSC triggered G2/M cell cycle arrest and decreased the cell clone formation. A mouse xenograft model revealed that OSC inhibited tumor growth in vivo. Findings of serum metabolomics analyses indicated that the anticancer function of OSC was related to disorders of glutamine metabolism. Such a speculation was further verified by the expression level of GLUD1, which was downregulated by OSC treatment. Concentrations of the related metabolites α-KG and NADH were reduced in response to OSC treatment. Moreover, OSC led to disorganization of the mitochondrial ultrastructure and a decrease in mitochondrial membrane potential. OSC also decreased ATP production via oxidative phosphorylation (OXPHOS) but did not affect glycolysis in NSCLC cells. CONCLUSION: The key role of OSC in mitochondrial energy metabolism in NSCLC cells is to suppress tumor development and cell proliferation downregulating GLUD1 to inhibit the glutamine/glutamate/α-KG metabolic axis and OXPHOS. It indicats that OSC might be a potential natural agent for personalized medicine and an anticancer metabolic modulator in NSCLC chemotherapy.

Plant polypeptides: A review on extraction, isolation, bioactivities and prospects.

The application of traditional Chinese medicine has a long history in China with unique advantages and functions. With the rapid development of separation and purification technologies, more and more polypeptide compounds with specific biological activity and medicinal value were isolated from natural plants. The plant polypeptides have a lot of biological activities, such as antitumor effect, antioxidize effect, antibacterial effect, hypoglycemic effect, blood pressure lowering effect, lipid-lowering effect, anti-fatigue effect, and so on. This review summarized the extraction method, purification method, biological activities, and prospects of plant polypeptides, providing a basis for further study of plant polypeptides.

A new anti-tumor cytotoxic triterpene from Ganoderma lucidum.

Ganoderma lucidum (G. lucidum) is a famous medicinal fungus used as a traditional medicine for generations in China. Among bioactivities that G. lucidum possesses, the anti-tumor effect has aroused extensive interests. In this study, one new triterpene (1) was isolated from 90% ethanol extract of the dried fruiting bodies of G. lucidum. Its structure was determined based on the analysis of its spectroscopic data, including 1 D and 2 D NMR and MS spectra. Furthermore, 1 elicited moderate anti-tumor activities (IC50 values of 15.38 ± 0.34 and 18.61 ± 0.55 µM for A549 and HepG2 cells, respectively) compared with cisplatin which was employed as the positive drug with IC50 values of 8.21 ± 0.17 and 5.36 ± 0.29 µM for A549 and HepG2 cells, respectively. The mechanism study by RT-qPCR and western blot analysis suggested that the p53/caspase-3 pathway is involved in the 1-induced apoptosis.

Plasma Metabolomics for Discovery of Early Metabolic Markers of Prostate Cancer Based on Ultra-High-Performance Liquid Chromatography-High Resolution Mass Spectrometry.

BACKGROUND: The prevention and early screening of PCa is highly dependent on the identification of new biomarkers. In this study, we investigated whether plasma metabolic profiles from healthy males provide novel early biomarkers associated with future risk of PCa. METHODS: Using the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, we identified plasma samples collected from 146 PCa cases up to 13 years prior to diagnosis and 272 matched controls. Plasma metabolic profiles were characterized using ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). RESULTS: Orthogonal partial least squares discriminant analysis (OPLS-DA) discriminated PCa cases from controls, with a median area under the receiver operating characteristic curve (AU-ROC) of 0.92 using a 1000-time repeated random sub-sampling validation. Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) identified the top 10 most important metabolites (p < 0.001) discriminating PCa cases from controls. Among them, phosphate, ethyl oleate, eicosadienoic acid were higher in individuals that developed PCa than in the controls during the follow-up. In contrast, 2-hydroxyadenine, sphinganine, L-glutamic acid, serotonin, 7-keto cholesterol, tiglyl carnitine, and sphingosine were lower. CONCLUSION: Our results support the dysregulation of amino acids and sphingolipid metabolism during the development of PCa. After validation in an independent cohort, these signatures may promote the development of new prevention and screening strategies to identify males at future risk of PCa.

Identification of novel CDK 9 inhibitors based on virtual screening, molecular dynamics simulation, and biological evaluation.

AIMS: Cyclin-dependent kinase 9 (CDK9) is a member of the CDK subfamily and plays a major role in the regulation of transcriptional elongation. It has attracted widespread attention as a therapeutic target for cancer. Here, we aimed to explore novel CDK 9 inhibitors by using a hybrid virtual screening strategy. MAIN METHODS: A hybrid virtual screening strategy was constructed with computer-aided drug design (CADD). First, compounds were filtered in accordance with Lipinski's rule of five and adsorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Second, a 3D-QSAR pharmacophore model was built and used as a 3D query to screen the obtained hit compounds. Third, the hit compounds were subjected to molecular docking studies. Fourth, molecular dynamics (MD) simulations were performed on CDK9 in complex with the final hits to examine the structural stability. Finally, CDK9 kinase biochemical assay was performed to identify the biological activity of the hit compounds. KEY FINDINGS: Seven hit compounds were screened out. These hit compounds showed drug-like properties in accordance with Lipinski's rule of five and ADMET. Complexes involving the six hit compounds bound to CDK9 exhibited good structural stability in the MD simulation. Furthermore, these six hit compounds had strong inhibitory activity against CDK9 kinase. In particular, hit 3 showed the most promising activity with the percentage of 71%. SIGNIFICANCE: The six hit compounds may be promising novel CDK9 inhibitors, and the hybrid virtual screening strategy designed in this study provides an important reference for the design and synthesis of novel CDK9 inhibitors.

[Effect of acupuncture and moxibustion on severe obesity complicated with hyperlipidemia in different genders].

OBJECTIVE: To explore the effect of acupuncture and moxibustion on severe obesity complicated with hyperlipidemia in different genders and their comprehensive effect, lipid indexes, and obesity indexes. METHODS: A total of 264 patients of severe obesity complicated with hyperlipidemia were assigned into a male group (106 cases) and a female group (158 cases)．According to their clinical symptoms and patterns, acupuncture and moxibustion differentiation therapies were applied for stomach and intestine heat type, spleen deficiency and dampness resistance type, phlegm-dampness internal resistance type, liver depression and spleen deficiency type, spleen and kidney yang deficiency type and yin deficiency and blood stasis type．The obesity indexes were weight (W), obesity degree (A), body mass index (BMI) and body fat percentage (F); the blood lipid indexes were total cholesterol (TC)，triglyceride (TG)，low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C). The comprehensive effect, obesity and blood lipid indexes were observed．. RESULTS: The total effective rate of the male group was 91.5% (97/106), and the total effective rate of the female group was 85.4% (135/158) , without statistical significance (R>0.05). After treatment, the obesity indexes of W, A, BMI and F and the blood lipid levels of TC, TG, LDL-C decreased, the levels of HDL-C increased compared with those before treatment in the two groups (P<0.05, P<0.01). The different values before and after treatment of the above all indexes in the male group were higher than those in the female group (all P<0.05). CONCLUSION: Acupuncture and moxibustion can both improve the obesity and blood lipid indexes for the patients with obesity complicated with hyperlipidemia. The effect is better for male than for female. The methods can prevent and treat hyperlipidemia.

[Lab-scale SNAD Process in Wastewater Treatment Plant].

Outside the municipal waste water treatment plant(WWTP) which located in Mentougou District, Beijing, the effluent of the anoxic/oxic(A/O) phosphorus removal process served as the substrate to operate a completely autotrophic nitrogen removal over nitrite(CANON) filter reactor.. After the reactor was successfully activated, glucose was added to the influent as the organic carbon source. The simultaneous partial nitrification, anaerobic ammonium oxidation (ANAMMOX), and denitrification (SNAD) process was started to study the effect of SNAD filter on sewage treatment. The results showed that from 119 d to 128 d, the ammonia removal rate of the CANON process was more than 95%, and the maximum total nitrogen concentration in the effluent was 13.0 mg·L-1. Total nitrogen concentration surpassed the 1A level of the Integrated Discharge Standard of Water Pollutants applied in Beijing City. The SNAD process was started by adding glucose to the influent at 129 d. The total nitrogen removal rate of this process was about 85% at 133-187 d, and the total nitrogen concentration in the effluent was 5.5-7.3 mg·L-1. The filter plugged up at 195 d, and backwash was utilized at 196 d. During the subsequent 30 d, the total nitrogen removal rate of the reactor was greater than 85%, and the total nitrogen concentration in the effluent remained at 6.2-7.2 mg·L-1. Compared with the CANON process, the SNAD process improved the total nitrogen removal rate and reduced the total nitrogen concentration of the effluent by 6 mg·L-1. The ammonia and total nitrogen concentrations in effluent satisfied the 1A level of the Integrated Discharge Standard of Water Pollutants.

[Impact on the lipid level of obesity of spleen deficiency and damp blockage complicated by hyperlipemia treated with warm needling therapy and auricular acupuncture].

OBJECTIVE: To explore the efficacy on obesity of spleen deficiency and damp blockage pattern and hyperlipemia treated with warm needling therapy and auricular acupuncture and the effect mechanism of the combined treatment. METHODS: One hundred and ten patients of obesity of spleen deficiency and damp blockage pattern and hyperlipemia were randomized into an observation group and a control group, 55 cases in each one. Additionally, a healthy group (52 cases) was set up as the control. In the control group, the warm needling therapy was applied to Taibai (SP 3), Chongyang (ST 42), Yinlingquan (SP 9), Zusanli (ST 36), etc., once every two days. In the observation group, on the basic treatment as the control group, the auricular acupuncture was applied to Pi (CO13), Wei (CO4), Fei (CO14), Shen (CO10), etc., once every 2 to 3 days. The efficacy was evaluated after 3-month, treatment in the two groups. The observation was conducted on the obesity outcomes [body mass, obesity degree (A), body mass index (BMI), body fat percentage (F%)], blood-lipoids indicators [such as serum total cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C)], fat-islet endocrine axis outcomes [such as fasting plasma glucose (FPG) , fasting leptin (FLP), fasting insulin (FINS), insulin sensitivity index (ISI), insulin resistance index (Homa-IR) and insulin ß cell function index (Homa-ß)], as well as autonomic nerve function index (Y) before and after treatment in the patients of the two groups. The efficacy was assessed in the two groups. RESULTS: The total effective rate was 96.4% (53/55) in the observation group, better than 87.3% (48/55, P < 0.01) in the control group. For the improvements of the obesity indices, the differences were not significant between the two groups (all P > 0.05). Before treatment, the levels of TC, TG, LDL-C, FLP, FPG, FINS and Homa-IR in the two groups were all significantly higher than those in the healthy group (all P < 0.01), and the levels of HDL, ISI, Homa-ß and Y were significantly lower than those in the healthy group (all P < 0.01). After treatment, except Homa-ß, the other indices were all improved significantly (all P < 0.01). The results in the observation group were better than those in the control group (all P < 0.01). CONCLUSION: The patients of obesity of spleen deficiency and damp blockage pattern and hyperlipemia have the disturbances of lipid metabolism, "fat-islet endocrinal axis" function and automatic nerve function. The combined treatment of warm needling therapy and auricular acupuncture or simple warm needling therapy present the effects of weight reducing and lipid reducing. The effect of the combined treatment is better than simple warm needling therapy. The efficacy mechanism is probably relevant to the positive regulation of blood glucose, lipid metabolism, fat-islet endocrinal axis and automatic nerve function.

[Effects of electroacupuncture for visceral fat of simple obesity with stomach and intestinal heat].

OBJECTIVE: To observe the clinical effect of electroacupuncture (EA) for visceral fat of simple obesity with stomach and intestinal heat. METHODS: Forty patients (waistline of male ≥ 90 cm and female ≥ 80 cm) were treated with EA at Quchi (LI 11), Zusanli (ST 36), Xiajuxu (ST 39), Shangjuxu (ST 37), Neiting (ST 44), Qiangu (SI 2), Erjian (LI 2), Tianshu (ST 25) and Fenglong (ST 40) for continuous 3 courses (12 treatments as 1 course) once every other day. The observation items before and after treatment were obesity indices[body weight (W), obesity degree (A%), body mass index (BMI), body fat percentage (F%, skinfold thickness me-thod)], body circumference indices (chest measurement, waistline, hip circumference, thigh circumference, waist-to-hip ratio) and body composition indices[body fat percentage (F%), body moisture content ratio, visceral fat cross assessment index (VFA)]. Besides, 40 healthy control subjects with similar ages and gender ratio were recruited as control. RESULTS: The total effective rate of the observation group was 97.5% (39/40), with lower W, A%, F%, BMI, chest measurement, waistline, hip circumference, thigh circumference, waist-to-hip ratio and VFA as well as higher body moisture content ratio after treatment (all P<0.01). While there was statistical significance between the two groups for all the indices after treatment (all P<0.01). CONCLUSIONS: EA can induce body weight and visceral fat of simple obesity with stomach and intestinal heat as well as improve body composition. Besides, body moisture ratio increases.

[Effects of acupuncture on 1528 patients with obesity complicated with hyperlipidemia in different obesity levels].

OBJECTIVE: To observe the clinical effect of acupuncture on obesity complicated with hyperlipidemia, and to explore the therapeutic differences among patients with different obesity levels. METHODS: A total of 1528 patients of obesity complicated with hyperlipidemia were enrolled into the study. According to the clinical symptoms and signs, they were treated with acupuncture according to the syndrome differentation. According to their obesity levels (A), body mass index (BMI) and body fat percentage (F%) before treatment, they were assigned into a mild obesity group, a moderate obesity group and a severe obesity group. The obesity index of body weight, A, BMI and F%, the blood lipid levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) were observed before and after treatment. The total efficacy, weight loss effect and lipid-lowering effect were evaluated. RESULTS: ① The constituent ratio of severe obesity in male patients overweighted that of female patients (P<0.01), and the obesity was positively correlated with age and disease duration (r=0.145 and 0.164, both P<0.01). ② After treatment, the total effective rate was 98.9% (461/466), the weight loss rate was 99.4% (463/466) and lipid-lowering rate was 99.1% (462/466) in the mild obesity group, which were the all highest among three groups, indicating the lower obesity level achieved the better acupuncture efficacy. ③ Acupuncture can significantly regulate the obesity index and blood lipid levels (all P<0.01); the obesity was negatively correlated with BMI and HDL-C (all P<0.01), and positively correlated with F%, TC, TG and LDL-C (all P<0.01). CONCLUSIONS: Acupuncture has dual effects on obesity and hyperlipidemia, which is significantly effective for patients with different obesity levels; acupuncture has the optimal effect on mild obesity, and had the optimal regulation on F% and blood lipid levels on severe obesity; acupuncture has superior overall regulation effects on obesity complicated with hyperlipidemia.

Review of systematic reviews and Meta-analyses investigating Traditional Chinese Medicine treatment for type 2 diabetes mellitus.

OBJECTIVE: To conduct a review of the systematic reviews and meta-analyses on the Traditional Chinese Medicine (TCM) treatment of type 2 diabetes mellitus (T2DM). METHODS: We searched PubMed, Cochrane, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang, and other databases from database inception to May 2014 for systematic reviews and meta-analyses on TCM treatment of T2DM. Manuscripts were read by two investigators if they met the inclusion criteria, and data were extracted. A Measurement Tool to Assess Systematic Reviews (AMSTAR) was used to classify research quality, and the evidence quality was graded by the Grade of Recommendation, Assessment, Development, and Evaluation (GRADE) system. RESULTS: Eighteen systematic reviews and meta-analyses were considered. Fifteen analyzed the efficacy of Chinese herbal medicines, and three investigated the efficacy of acupuncture. AMSTAR evaluation ranged from 3-10, and re-evaluation of the main results implied that treatment of T2DM with TCM has certain advantages when compared with conventional Western medicine. However, the evidence quality was generally low. CONCLUSION: This work shows favorable evidence for the clinical treatment of TCM on T2DM. However, it is recommended that evidence-based decisions are made based on clinical trials because of the GRADE scores of the studies. To achieve higher quality of clinical research, clinical research on TCM requires specific and suitable research methods. Further trials may increase the quality of evidence to evaluate the clinical efficacy of TCM for T2DM.

[Analysis on the academic cultivation of young TCM scholars based on Professor LIU Zhicheng's academic track].

In view of the public academic papers of Professor LIU Zhicheng, his academic track is analyzed, including validating effect, exploring mechanism, improving efficacy, expanding disease variety, deepening mechanism, optimizing program and seeking breakthrough. On this basis, combined with the self-character of TCM, the potential path for the academic cultivation of young scholars is refined: focusing on clinical practice, confirming clinical efficacy, deepening mechanism exploration, improving clinical therapeutic effect, optimizing clinical program, extending clinical disease spectrum, inheriting, seeking, breaking through, innovating, expecting and topping over. It is believed that during the academic cultivation, the importance is to form the stable research direction and continuity, organize research team, absorb actively new knowledge and thoughts, and adopt multidisciplinary cross and coordination so as to achieve the greater success ultimately.

[Clinical observation on obesity and hyperlipidemia of yang deficiency of spleen and kidney syn- drome in female patients treated with warm acupuncture combined with auricular acupuncture].

OBJECTIVE: To compare the differences of clinical effects in female patients with obesity and hyperlipidemia of yang deficiency of spleen and kidney syndrome between warm acupuncture combined with auricular acupuncture and simple warm acupuncture. METHODS: One hundred and thirty patients were randomly divided into an observation group and a control group, 65 cases in each one. In the control group, acupuncture was used at Pishu (BL 20), Zhongwan(CV 12), Shenshu(BL 23), Zhongji(CV 3), Guanyuan(CV 4), Mingmen(GV 4), Taibai(SP 3), Fenglong(ST 40), etc.; warm acupuncture was applied at Pishu(BL 20), Zhongwan(CV 12), Shenshu(BL 23) and Zhongji(CV 3); the treatment was required once every two days and for 3 months continuously. In the observation group, based on the treatment in the control group, thumbtack intradermal needles were embedded at auricular points, including pi(CO13), shen(CO10), pangguang(CO9), sanjiao(CO17), neifenmi(CO18), neishengzhiqi(TF2), etc. Obesity indices [body mass(W), obesity degree(A), body mass index(BMI), body fat percentage(F%)] blood lipid indices [serum total cholesterol(TC), triglyceride(TG), low density lipoprotein(LDL-C), high density lipoprotein(HDL-C)] and clinical efficacy were observed before and after treatment in the two groups. Results After treatment in the two groups, the obesity indices of W, A, BMI, F% and the blood lipid levels of TC, TG, LDL-C were obviously decreased compared with those before treatment (all P<0. 01) and the HDL-C levels were apparently increased than those before treatment (both P<0. 01). After treatment, the improvement of TC and HDL-C in the observation group was superior to that in the control group (both P<0. 01). The difference was not statistically significant in the aspect of improving every obesity index between two groups (all P>. 05). The comprehensive total effective rate of the observation group was 95.4% (62/65), which was better than 84. 6% (55/65) of the control group (P<0. 001). CONCLUSION: Warm acupuncture combined with auricular acupuncture and simple warm acupuncture can both benignly adjust abnormal lipid metabolism of obesity patients with hyperlipidemia, and warm acupuncture combined with auricular acupuncture are superior to simple warm acupuncture treatment on antiobesity action and improving the TC and HDL-C levels.

[Efficacy observation of acupuncture and tapping therapy in the treatment of type 2 diabetes of yin deficiency pattern combined with stasis in the patients].

OBJECTIVE: To explore the clinical efficacy and mechanism of acupuncture and tapping therapy in the treatment of type 2 diabetes of yin deficiency pattern combined with stasis in the patients. METHODS: One hundred and twelve patients were treated with acupuncture, followed by tapping method. The reinforcing method with lifting, thrusting and rotating needle technique was used at Taixi (KI 3), Shenmen (HT 7), Taibai (SP 3), Taiyuan (LU 9), Sanyinjiao (SP 6) and Zusanli (ST 36); and the even-needling technique was used at Taichong (LR 3), Hegu (LI 4), Xuehai (SP 10) and Fenglong (ST 40). The needles were remained for 30 min. After needle removal, the tapping method with plum-blossom needle was applied to Geshu (BL 17), Yishu (EX-B 3), Ganshu (BL 18), Shenshu (BL 23) and Pishu (BL 20), once every two days. The treatment of 3 months was required. The changes were observed before and after treatment in the relevant indices of fat-islet axis such as fasting plasma glucose (FPG), fasting leptin (FLP), fasting insulin (FINS), insulin sensitivity index (ISI), insulin resistance (Homa IR), insulin secretion index (Homa-beta) and the indices of obesity and blood lipids in the patients. RESULTS: After treatment, the total effective rate was 84.8% (95/112), in which the efficacy on the stasis predominated syndrome was better than that of yin deficiency predominated syndrome [92.9% (52/56) vs 76.8% (43/56), P < 0.05]. Before treatment, FPG, FLP, FINS, Homa-IR, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), body mass, body mass index (BMI), fat percentage (F%) and obesity degree in the patients were higher obviously than those in the normal group (all P < 0.01); high-density lipoprotein cholesterol (HDL-C) and ISI were lower than those in the normal group (both P < 0.01). After treatment, FPG, FLP, FINS, Homa-IR, TC, TG, LDL-C, body mass, BMI, F% and obesity degree were all reduced obviously as compared with those before treatment (all P < 0.01). ISI and HDL-C were increased apparently (both P < 0.01). The efficacy on mild obesity was superior to that on moderate and severe obesity, and the efficacy in the young patients was better than that in the elderly, the efficacy in the males was better than that in the females, but the differences were not significant (all P > 0.05). The efficacy in the cases with 10 years duration of sickness was superior to those with over 10 years duration of sickness (P < 0. 01). CONCLUSION: Acupuncture and tapping therapy achieves the significant efficacy on type 2 diabetes of yin deficiency pattern combined with stasis and its effect mechanism is related to the positive regulation of glucose, lipid metabolism and fat-islet axis.

Neuroprotection against Aß25-35-induced apoptosis by Salvia miltiorrhiza extract in SH-SY5Y cells.

The neurotoxicity of ß-amyloid protein (Aß) contributes significantly to the pathogenesis of Alzheimer's disease (AD), and hence the attractive therapeutic strategies focusing on the modulation of Aß-induced neurotoxicity are warranted. The present study aims to investigate the neuroprotection and underlying mechanisms by which Salvia miltiorrhiza Bunge (Lamiaceae) extract (SME) protects against Aß25-35-induced apoptosis in SH-SY5Y cells. 2h Pre-treatment of SH-SY5Y cells with SME (0.01, 0.1 or 0.2mg raw herb/ml) concentration-dependently attenuated Aß25-35-induced cell death, as evidenced by the increase in cell viability and decrease in neuronal apoptosis. In addition, SME suppressed the increased intracellular reactive oxygen species levels, decreased the protein expression of cleaved caspase-3, cytosolic cytochrome c, and Bax/Bcl-2 ratio. These findings taken together suggest that SME provides substantial neuroprotection against Aß25-35-induced neurotoxicity in SH-SY5Y cells, at least in part, via inhibiting oxidative stress and attenuating the mitochondria-dependent apoptotic pathway. The approach used in this study may also be useful for the screening of therapeutic agents for AD and other related neurodegenerative disease.