The Mechanism of Rac1 in Regulating HCC Cell Glycolysis Which Provides Underlying Therapeutic Target for HCC Therapy.

Aim: To explore the role of Rac1 on sorafenib resistance in hepatocellular carcinoma. Methods: CCK-8, wound healing assay, Transwell, and cell cycle assay were used to detect the tumor cells development. Cell viability was assessed by MTT. The glycolytic pathway was revealed by cellular metabolism assays. Result: We recovered that Rac1 upregulation was related to HCC patients' poorer prognosis. Forced expression of Rac1 promoted cell development and sorafenib chemoresistance in HCC cells. Rac1 inhibitor EHop-016 and sorafenib combination markedly prevented cell viability, G2/M phase cycle arrest, and apoptosis than single therapy. Furthermore, combination therapy decreased glycolysis in HCC cells. In vivo, the tumor growth was significantly prevented by combination therapy single therapy. Conclusion: Our research declares that Rac1 inhibition could block sorafenib resistance in HCC by decreasing glycolysis, which would provide an underlying target for HCC therapy.

[Exploration and practice of micro-video teaching of Characteristic Clinical Technology of Acupuncture and Moxibustion].

In this paper, the micro-video teaching mode was explored in the course construction of Characteristic Clinical Technology of Acupuncture and Moxibustion. The micro-video teaching contents include the academic thought, experience in diagnosis and treatment, characteristic technology and clinical manipulation of famous acupuncture experts in the Henan University of CM. Each micro-video film is designed within 15-18 min, including three sections of knowledge, i.e. basic theory, technological application and clinical manipulation. Each section is designed within 5-6 min. The construction of the teaching course of Characteristic Clinical Technology of Acupuncture and Moxibustion is the innovation of practice mode of TCM and the new approach to the inheritance of the experience of experts. The construction of micro-video teaching course propels the reform of teaching mode, improves the learning initiative of students and clinical manipulative ability so as to improve the teaching effect and quality.

A Systematic Inflammation-based Model in Advanced Pancreatic Ductal Adenocarcinoma.

Emerging evidence revealed the critical role of systematic inflammation in pancreatic ductal adenocarcinoma (PDAC). In the present study, we reviewed the records of 279 patients with advanced PDAC. Among them, 147 cases were used as the training cohort and another 132 as the validation cohort. In the training cohort, distant metastasis, carbohydrate antigen 19-9 (CA19-9), Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR) were independent prognostic factors in Cox regression. A nomogram based on these factors was generated to predict median survival time and survival probabilities at 6, 12, and 18 months. The nomogram showed a better discriminatory ability than the American Joint Committee on Cancer (AJCC) TNM staging (C-index: 0.727 vs. 0.610). In the validation cohort, a nomogram composed of the same variables also showed a high discriminatory ability (C-index: 0.784). In the low-risk group with a nomogram total point (NTP) value of more than 175, patients receiving combination therapy showed better prognosis than those receiving monotherapy (P=0.015). In conclusion, the nomogram based on inflammatory biomarkers can serve as useful prognostic tool for advanced PDAC. In addition, patients with high NTP can greater benefit from combination chemotherapy than monotherapy.

IL-1α induces apoptosis and inhibits the osteoblast differentiation of MC3T3-E1 cells through the JNK and p38 MAPK pathways.

Interleukin (IL)-1 is a proinflammatory cytokine that plays important roles in inflammation and host responses to infection. The present study aimed to evaluate the effects of IL-1α on the apoptosis and differentiation of osteoblasts, and to elucidate the mechanism responsible for these effects in the osteoblast­like cell line MC3T3-E1. The MC3T3-E1 cells were non-treated or treated with IL-1α. Following treatment, cell viability, alkaline phosphatase (ALP) activity and caspase-3 activity were evaluated. The expression of osteoblast-specific genes as well as Bax, Bcl-2 and caspase-3 were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein levels of Bax, Bcl-2, caspase-3 and the phosphorylation of mitogen-activated protein kinases (MAPKs, also known as MAP kinases) were evaluated using western blot analysis. The MAPK signaling pathway was blocked by pre-treatment with MAPK inhibitors SB203580, PD98059 and SP600125. IL-1α treatment induced a significant decrease in cell viability and ALP activity in the MC3T3-E1 cells. IL-1α also significantly decreased the mRNA expression and protein levels of osteoblast-related genes in the MC3T3-E1 cells. On the other hand, IL-1α significantly upregulated the mRNA expression and protein levels of Bax and caspase-3 as well as caspase-3 activity, whereas Bcl-2 expression was decreased in the MC3T3-E1 cells. Furthermore, IL-1α activated the apoptotic signaling pathway by increasing the phosphorylation of c-Jun N-terminal kinase (JNK) and p38-MAPK, whereas it inhibited the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Moreover, pre-treatment with MAPK inhibitors attenuated the phosphorylation of JNK, p38 and Bax expression enhanced by IL-1α. However, MAPK inhibitors markedly increased the protein expression of osteoblast-related genes and Bcl-xL in the MC3T3-E1 cells downregulated by IL-1α. Taken together, these findings suggest that IL-1α induces the apoptosis of osteoblasts and inhibits osteoblast differentiation by activating the JNK and the p38 MAPK pathways.

Adenovirus-mediated downregulation of the ubiquitin ligase RNF8 sensitizes bladder cancer to radiotherapy.

The ubiquitin ligase RNF8 promotes the DNA damage response (DDR). We observed that the expression of RNF8 was increased in bladder cancer cells and that this change in RNF8 expression could be reversed by adenovirus-mediated shRNA treatment. Moreover, we found that RNF8 knockdown sensitized bladder cancer cells to radiotherapy, as demonstrated by reduced cell survival. Additionally, the absence of RNF8 induced a high rate of apoptosis and impaired double-strand break repair signaling after radiotherapy. Furthermore, experiments on nude mice showed that combining shRNF8 treatment with radiotherapy suppressed implanted bladder tumor growth and enhanced apoptotic cell death in vivo. Altogether, our results indicated that RNF8 might be a novel target for bladder cancer treatment.

A survey of the practice and perspectives of chinese acupuncturists on deqi.

Deqi refers to the special sensation and reaction sensed mainly by both acupuncturist and patient when a needle was inserted into the acupoints and is considered to be vital to achieve acupuncture effect. For acupuncturist, it is important to judge and control Deqi in clinical practice. However, enough attention is paid to patients' feelings rather than acupuncturists' nowadays. We thus conducted this survey to determine acupuncturists' perspectives about Deqi and to further find the proper way to induce Deqi. A total of 250 questionnaires were sent out to acupuncturists and 202 (80.8%) were returned. According to the results, most acupuncturists believe that Deqi is vital to obtain preferable clinical effects. The reliability of acupuncturists' Deqi sensation ranks as sinking> tightening> astringent. The reliability of patients' Deqi sensations ranks as sourness> numbness> distention> heaviness> pain. The reliability of influential factors ranks as manipulation> specificity of acupoint> TCM constitution> disease status> patient's psychological condition> acupuncturists' psychological guidance> clinical environment. This study is believed to provide additional evidence to the qualitative and quantitative research of Deqi in the future.

[Comparison of the therapeutic effect on skeletal fluorosis and impact on urine fluoride value among fire needle therapy, electroacupuncture and calcium carbonate D3].

OBJECTIVE: To observe the impacts on skeletal fluorosis pain, joint motor dysfunction and urine fluoride excretion in the treatment with fire needle therapy, electroacupuncture and calcium carbonate D3. METHODS: The randomized controlled trial was adopted. Ninety-five patients were randomized into a fire needle group (31 cases), an electroacupuncture group (33 cases) and a calcium carbonate D3 group (31 cases). In the fire needle group and the electroacupuncture group, Ashi points, Dazhui (GV 14), Geshu (BL 17), Quchi (LI 11), Hegu (LI 4), Xuehai (SP 10) points were selected and stimulated with fire needle and electroacupuncture separately, three times a week. In the calcium carbonate D3 group, calcium carbonate D3 tablets was prescribed for oral administration, 600 mg each time, twice a day. The duration of treatment was 2 months in the electroacupuncture group and calcium carbonate D3 group and 1 month in the fire needle group. VAS score, the range of motion (ROM) and urine fluoride value were compared before and after treatment in the patients of the three groups. RESULTS: After treatment, VAS value and ROM were improved significantly in the patients of the three groups (all P < 0.05), the difference was not significant in comparison of the three groups (all P > 0.05). After treatment, the urine fluoride value was increased significantly in the fire needle group [(7.89 +/- 3.61) mg/L vs (9.81 +/- 4.17) mg/L, P < 0.01] and was increased in the electroacupuncture group [(7.53 +/- 3.46) mg/L vs (8.97 +/- 4.21) mg/L, P < 0.05]. The difference was not significant in comparison before and after treatment in the calcium carbonate D3 group (P > 0.05). CONCLUSION: The fire needle therapy, electroacupuncture and calcium carbonate D3 all have the clinical value in the prevention and treatment of skeletal fluorosis and the difference in the therapeutic effect has not been discovered among them yet at present. But it has been found that the fire needle therapy and electroacupuncture display the active significance in the promotion of urine fluoride excretion.

[Inhibitory effect of exogenous insulin-like growth factor binding protein 7 on proliferation of human breast cancer cell line MDA-MB-453 and its mechanism].

The present study was to investigate the effects of exogenous insulin-like growth factor binding protein 7 (IGFBP7) on the proliferation of human breast cancer cell line MDA-MB-453 and its possible mechanism. By means of MTT method in vitro, the results showed exogenous IGFBP7 inhibited the growth of MDA-MB-453 cells (IC50 of IGFBP7 = 8.49 µg/mL) in time- and concentration-dependent manner. SB203580, p38(MAPK) inhibitor, blocked the anti-proliferative effect of exogenous IGFBP7. The flow cytometry assay showed that exogenous IGFBP7 remarkably induced G0/G1 arrest in MDA-MB-453 cells. The Western blot showed that exogenous IGFBP7 promoted phosphorylation of p38(MAPK), up-regulated expression of p21(CIP1/WAF1), and inhibited phosphorylation of Rb. SB203580 restrained exogenous IGFBP7-induced regulation of p21(CIP1/WAF1) and p-Rb in MDA-MB-453 cells. In conclusion, the present study suggests that exogenous IGFBP7 could activate the p38(MAPK) signaling pathway, upregulate p21(CIP1/WAF1) expression, inhibit phosphorylation of Rb, and finally induce G0/G1 arrest in MDA-MB-453 cells.

Synthesis, molecular modeling and biological evaluation of chalcone thiosemicarbazide derivatives as novel anticancer agents.

A series of novel chalcone thiosemicarbazide derivatives (4a-4x) have been designed, synthesized, structurally determined, and their biological activities were also evaluated as potential EGFR kinase inhibitors. All the synthesized compounds are first reported. Among the compounds, compound 4r showed the most potent biological activity (IC(50) = 0.78 ± 0.05 µM for HepG2 and IC(50) = 0.35 µM for EGFR), which is comparable to the positive controls. Docking simulation was also performed to position compound 4r into the EGFR active site to determine the probable binding model. Antiproliferative assay results demonstrated that some of these compounds possessed good antiproliferative activity against HepG2. Compound 4r with potent inhibitory activity in tumor growth inhibition may be a potential anticancer agent.

Association of serum uric acid with different levels of glucose and related factors.

BACKGROUND: Previous studies have demonstrated that serum uric acid (UA) is an independent predictor of incident type 2 diabetes mellitus (T2DM) in general populations. This study aimed to investigate specific characteristics of UA and its relationship between UA and blood glucose and other risk factors in the Chinese population. METHODS: A total of 946 subjects were included in this study. UA, glucose, insulin, fractional excretion of UA (FEua), creatinine clearance rate (Ccr), hemoglobin A1c (HbA1c), fructosamine (FA), blood pressure and lipids were studied and also reexamined after the patients underwent two weeks of combined therapeutics. RESULTS: UA levels were the highest in subjects with impaired glucose regulation (IGR), followed by subjects with normoglycemia (NGT) and finally by subjects with T2DM. The level of the 2-hour postprandial insulin and the area under the curve for insulin (AUCins) showed a similar tendency. The UA levels initially increased with increasing fasting blood glucose (FBG) and postprandial blood glucose (PPBG) levels, up to 7 mmol/L and 10 mmol/L, respectively, and thereafter decreased at higher FBG and PPBG levels. Compared with subjects in the lower serum UA quartile, subjects in the upper quartile of serum UA levels had higher weights, triglyceride levels, and creatinine levels as well as lower Ccr and FEua levels. Compared with women's group, UA levels were higher, and FEua levels were lower in men's group. Sex, body mass index (BMI), mean arterial blood pressure (MAP), serum triglycerides (TG), FA and Ccr were independent correlation factors of UA. UA decreased and FEua increased after the patients underwent a combined treatment. CONCLUSIONS: UA increased initially and then decreased as glucose levels increased from NGT to IGR and T2DM. Compared with NGT and T2DM, IGR subjects had higher SUA levels, which related to its high levels of insulin. Under T2DM, male gender, BMI, MAP, Ccr, TG and FA are independent correlation factors of UA. Glucose-lowering, antihypertensive, lipemia-regulating combined treatments were of advantage to decline of SUA of T2DM.

Acupuncture as a treatment for functional dyspepsia: design and methods of a randomized controlled trial.

BACKGROUND: Acupuncture is widely used in China to treat functional dyspepsia (FD). However, its effectiveness in the treatment of FD, and whether FD-specific acupoints exist, are controversial. So this study aims to determine if acupuncture is an effective treatment for FD and if acupoint specificity exists according to traditional acupuncture meridians and acupoint theories. DESIGN: This multicenter randomized controlled trial will include four acupoint treatment groups, one non-acupoint control group and one drug (positive control) group. The four acupoint treatment groups will focus on: (1) specific acupoints of the stomach meridian; (2) non-specific acupoints of the stomach meridian; (3) specific acupoints of alarm and transport points; and (4) acupoints of the gallbladder meridian. These four groups of acupoints are thought to differ in terms of clinical efficacy, according to traditional acupuncture meridians and acupoint theories. A total of 120 FD patients will be included in each group. Each patient will receive 20 sessions of acupuncture treatment over 4 weeks. The trial will be conducted in eight hospitals located in three centers of China. The primary outcomes in this trial will include differences in Nepean Dyspepsia Index scores and differences in the Symptom Index of Dyspepsia before randomization, 2 weeks and 4 weeks after randomization, and 1 month and 3 months after completing treatment. DISCUSSION: The important features of this trial include the randomization procedures (controlled by a central randomization system), a standardized protocol of acupuncture manipulation, and the fact that this is the first multicenter randomized trial of FD and acupuncture to be performed in China. The results of this trial will determine whether acupuncture is an effective treatment for FD and whether using different acupoints or different meridians leads to differences in clinical efficacy. TRIAL REGISTRATION NUMBER: Clinical Trials.gov Identifier: NCT00599677.

Translation and validation of the Nepean Dyspepsia Index for functional dyspepsia in China.

AIM: To assess the reliability and validity of the translated version of Nepean Dyspepsia Index (NDI) in Chinese patients with documented functional dyspepsia (FD). METHODS: The translation process included forward translation, back translation, pretest and cross-cultural adaptation. Reliability and validity of the translated version were examined by asking 300 subjects to complete the Chinese version of the NDI. The mean age of subjects was 39.24 years and 68.7% of the subjects were women. Internal consistency analysis with Cronbach's alpha was performed to test the reliability. Correlation analysis was used to assess the content validity. Factor analysis and structural equation models were used to assess the construct validity. RESULTS: The Cronbach's alpha coefficients ranged 0.833-0.960, well above the acceptable level of 0.70. Correlation analysis showed that each item had a strong correlation with the corresponding domain, but a weak correlation with other domains. Confirmatory factor analysis indicated that the comparative fit index was 0.94, higher than the acceptable level of 0.90. CONCLUSION: The Chinese version of the NDI is a reliable and valid scale for measuring health-related quality of life and disease severity in Chinese patients with FD.

[Current situation and prospects of scale application in acupuncture research in China].

In recent years, the standardized scales have been increasingly adopted for acupuncture researches, making leaps in both quality and quantity. By analyzing the current situation of scale application in acupuncture researches in the past five years, the present paper points out the major problems at present, including inadequate use of the scale, insufficiency of the scale in reflecting the advantages and characteristics of acupuncture and moxibustion as well as lack of confirmatory test of reliability and validity of the scales, and probes into the future study thinking.

[Observation on therapeutic effect of warming needle moxibustion on knee osteoarthritis of deficiency-cold type].

OBJECTIVE: To compare clinically therapeutic effects of warming needle moxibustion and simple acupuncture on knee osteoarthritis. METHODS: One hundred and twenty cases conformed with the diagnostic criteria of knee osteoarthritis with TCM kidney-yang deficiency and cold syndrome were randomly divided into a warming needle moxibustion group and a simple acupuncture group. Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36) and others were selected in the two groups. Their therapeutic effects were assessed with joint pain scale, knee osteoarthritis severity index scale and cold syndrome differentiation factors. RESULTS: Both warming needle moxibustion and simple acupuncture could alleviate pain of knee osteoarthritis, improve dysfunction of the knee joint, reduce symptoms. The clinically basic cured rate and the total effective rate were 32.1% and 96.4% in the warming needle moxibustion group, which were better than 7.4% and 92.6% in the simple acupuncture group. CONCLUSION: Warming needle moxibustion is an effective therapy for knee osteoarthritis with kidney-yang deficiency and cold type.

[Clinical study on combination of acupuncture, cupping and medicine for treatment of fibromyalgia syndrome].

OBJECTIVE: To observe the therapeutic effect of acupuncture at five mental points and moving cupping on the Hechelu of the back on fibromyalgia syndrome (FS). METHODS: Sixty-six cases who conformed to the criteria were randomly divided into the treatment group treated with acupuncture at five mental points, moving cupping on the Hechelu of the back and amitriptyline, and the control group treated with amitriptyline. Clinical therapeutic effects were assessed with McGill Pain Questionnaire (MPQ) and HAMD depression scale. RESULTS: The therapeutic effect of the treatment group was better than that of the control group with a significant difference between the two groups (P < 0.01). CONCLUSION: Combination of acupuncture with cupping therapy is an effective therapy for fibromyalgia syndrome.

[Clinical observation on the efficacy enhancing and toxicity attenuating effect of nuzhen yangyin granule to the anti-parkinsonism therapy mainly with Medopa].

OBJECTIVE: To observe and assess the efficacy enhancing and toxicity attenuating effect of Nuzhen Yangyin Granule (NYG) to the anti-parkinsonism (paralysis agitans) therapy with Medopa and Artane. METHODS: Adopting the randomized double-blinded method, the effect of adding NYG to 30 patients with Parkinsonism in the treated group, who already received anti-Parkinsonism treatment but showing decreased response to Medopa and Artane and with obvious adverse reaction, was observed and controlled by 30 patients treated by adding placebo. RESULTS: The total effective rate in the treated group and the control group was 86.7% and 56.7% respectively, the total syndrome improving rate was 90% and 56.7% respectively and the toxicity attenuating rate 90% and 43.3% respectively, comparison between the two groups showed significant difference (P < 0.05 or P < 0.01). NYG also showed markedly effective in reducing the adverse reactions of Medopa and Artane on digestive, neuro-psychiatric and cardiovascular system. CONCLUSION: NYG has obvious efficacy enhancing and toxicity attenuating effects caused by the anti-Parkinsonism treatment with Medopa and Artane.