The STAT3 protein is a key transcription factor that delivers extracellular signals into nuclei in which it binds to a specific recognition element on DNA sequences and thus regulates the transcription of its target genes.STAT3 is almost expressed in all tissues and cells, therefore, it is extensively involved in both normal and aberrant cellular activities.For example, STAT3 plays an essential role in inflammatory reaction and tumorigenesis.STAT3 has been established as a therapeutic target of various cancers including multiple myeloma,a hematological malignancy from plasma cells.Some STAT3 inhibitors have been developed and extensively studied.In this article, we review the roles of STAT3 in multiple myeloma.The advances and strategies in the development of STAT3 inhibitors are also being discussed.

ve To investigate the effects of clinical relevant concentrations of midazolam on whole-cell N-type calcium currents of sympathetic ganglion neurons trying to assess the involvement of sympathetic ganglion in circulation depression produced by midazolam. Methods 7-10 d SD rats were decapitated and bilateral superior cervical ganglions were rapidly removed and kept in 4℃, oxygen saturated incubation solution. TTX 1?mol/L and nifedipine 10 ?mol/L were added to the solution to block the Na+ and L-type calcium currents. Midazolam was also added to the solution. The final concentration of midazolam were 0.1, 0.3, 3, 10, 50, 100?mol/L.The effects of different concentration of midazolam on the whole-cell N-type calcium channel currents were assessed by patch-clamp technique. Results When the holding potential (Vh) was - 80mV and stimulating votage(Vt) was between - 30mV and 10mV midazolam inhibited the whole-cell N-type calcium currents dose-dependently ( r = 0.964, P

The advancement of research work on the carcinogenicity and its inhibition of 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific N-nitrosamine, was reviewed in the present paper. Carbonyl reduction and ?-hydroxylation were the major routes of NNK metabolic activation, the main target organ of NNK carcinogenicity was the lung and the carcinogenic probability related to the individual, organic isothiocyanates were the most potent inhibitors for NNK carcinogenicity. Eating more cruciferae vegetables and fruit and drinking more green and black tea would be helpful for smokers and passive smokers. Research about the nosogenesis and carcinogenicity and its inhibition of the harmful components in cigarette smoke should be further reinforced.

Objective Metabolic syndrome ( MS), a disorder involving multiple metabolic abnormalities such obesity,hypertension, diabetes or abnormal glucose tolerance and dyslipidemia, has been observed in many patients receiving coronary artery bypass procedures. In this study we try to examine the perioperative effects of metabolic syndrome on the off-pump coronary artery bypass (OPCABG). Methods A prospective study was conducted in 1060 consecutive OPCABG patients who were admited to Beijing Anzhen Hospital from July 2009 to March 2010. The patients were grouped as MS group and non-MS group according to the diagnostic criteria for Chinese metabolic syndrome. The outcomes such as mortality, atrial fibrillation,stroke, staying in ICU for more than three days, use of IABP, ECMO, dialysis, multiple organ dysfunction score ( MOOS) ,postoperative score for cardiac surgery (PSCS), PaO2/FiO2 , heart rate x central venous pressure/mean artery pressure(pressure-adjusted heart rate, PAHR) ,renal and liver function, platelets, and the dosage of vasoactive agents were analyzed and compared between the two groups by x2 test or t test. Results Three hundred and eighty-nine cases were diagnosed with MS among 1060 cases with OPCABG. In the MS group, 17 cases stayed in ICU for more than 3 days, 2 cases died, 76 had atrial fibrillation, 3 had stroke, 18 cases were treated with intra-aortic balloon counterpulsation (IABP). In the non-MS group, 47 cases stayed in ICU for more than 3 days, 12 cases died, 148 had atrial fibrillation, 3 had stroke, 48 cases were treated withIABP, 3 cases received ECMO and 4 cases received dialysis. No significant difference between MS group and non-MS group was identified in the aspects of mortality, atrial fibrillation, stroke, duration of more than three days in ICU, the use of IABP,ECMO, dialysis after OPACBG based on the x2 test(P＞0.05). However, on the operative days, the MODS and PSCS in MS group were significantly higher than that in non-MS group (P ＜ 0.05). MODS 2. 57 ± 1. 62 in MS group vs. 2. 15 ± 1.65 in non-MS group, PSCS 4.27 ±2.15 in MS group vs. 3.92 ±2.29 in non-MS group. PaO2/FiO2 in MS group was significantly lower than that in non-MS group (249.23 ± 110.99 vs. 283. 33 ± 114. 35), P ＜ 0. 01. PAHR in MS group was significantly higher than that in non-MS group (9.98 ±3.54 vs. 9.23 ±3. 88), P ＜0.05. On the first postoperative days, the MODS in MS group was also significantly higher than that in non-MS group (3.05 ±1.64 vs. 2.82 ± 1.72), P＜0.05. PaO2/FiO2 in MS group was significantly lower than that in non-MS group (277.11 ±122.99 vs.318.47 ±143.84), P＜0.05. Conclusion MS was not a predictor for death, atrial fibrillation, stroke, duration of more than three days in 1CU, the use of IABP, ECMO, dialysis after OPACBG. However, MS had a temporary adverse effect on the respiratory and circulatory systems on the operative day and the first postoperative day after OPCABG.

Aim The effects of diazepam on the whole cell sodium currents in rat sympathetic ganglion neurons were studied to investigate the mechanisms by diazepam mediates hypotension. Methods Whole cell patch clamp recordings were performed on enzymatically isolated rat superior cervical sympathetic ganglion neurons. Results Diazepam dose dependently blocked the whole cell sodium currents. Under a V t of 0 mV and a V h of 80 mV 0.3 ?mol?L -1 diazepam reduced sodium peak currents by 14.76 %(P

AIM: To study the interactions of propofol and midazolam on the whole cell sodium channel currents in rat sympathetic ganglion neurons. METHODS: Whole cell patch clamp recordings were made from enzymatically isolated rat (7- 10 d ) superior cervical sympathetic ganglion neurons. Isobolographic analysis was applied to evaluate the potency of combinations of propofol and midazolam on Na + channel currents. RESULTS: Under V h= 80 mV and V t= 0 mV . Propofol and midazolam dose dependently blocked Na + currents with a mean drug concentration required to produce 50% current inhibition (IC 50 ): 33.12 ?mol?L -1 and 18.35 ?mol?L -1 ; clinically relevant concentrations of propofol and midazolam reduced Na + peak currents by 27.66 % (P

AIM: To explore the influence of different concentration midazolam on the macroscopic voltage gated potassium currents and to discuss the relationship between potassium currents and inhibitory effect of clinical relevant concentration midazolam on sympathetic nervous system. METHODS: Superior sympathetic ganglion neurons were dissociated enzymatically from 7 to10 day old rat. Experiments were performed about 5 h after plating at room temperature (20- 24 ℃ ). Appropriate solution was chosen to separate the K + current from the other transmembrane currents. 1 ?mol?L -1 TTX was applied to the extracelluar solution to block the Na + current. Midazolam was also resolved in extracelluar solution to get various concentration ( 0.1 , 0.3 ,3,10,50,100 ?mol?L -1 ). Currents were recorded with the patch clamp technique in whole cell configuration using glass electrodes with a tip resistance of 2- 4 M . Potassium currents were evoked by test pulse from -100 mV to +30 mV with holding potential -80mV. Data were analyzed using Clampfit 6.0 and Oringih 5.0 software. Whole cell current records were corrected for leakage and capacitance by using the P/5 protocol. RESULTS: Midazolam dose dependently inhibited the whole cell potassium currents. Clinical relevant concentration midazolam ( 0.3 ?mol?L -1 ) only reduced the peak currents by 3.89 %(P= 0.88 ). The concentration required to produce 50% current inhibition(IC 50 ) was 76.065 ?mol?L -1 . CONCLUSION: Midazolam inhibits the whole cell potassium current significantly and dose dependently, but clinical relevant concentration midazolam has minor effect on the potassium currents, indicating that the inhibitory effect of midazolam on potassium current is not related to the suppression of activity of sympathetic system.

Objective:To analyze the factors related to metastasis of contralateral central lymph node (CLN) in cN0 papillary thyroid car-cinoma (PTC) and discuss the indications for CLN dissection. Methods:We enrolled 149 unilateral PTC patients who underwent total thyroidectomy and prophylactic bilateral (CLN) dissection. This work analyzed the relationship of gender, age, extrathyroidal extension, multifocality, thyroiditis, ipsilateral central lymph nodes, and prelaryngeal lymph node with CLNs. Results:The rates of metastasis to ip-silateral and contralateral central compartments were 73.2%and 23.5%, respectively. In univariate analysis, gender, age, tumor size, multifocality, and thyroiditis were not important in predicting contralateral central compartment lymph node metastasis (P=0.792, 0.097, 0.531, 0.269, and 1.000, respectively);by contrast, extrathyroidal extension (P=0.017), prelaryngeal lymph nodes (P=0.006), and ipsilateral CLNs (P<0.001) are related to CLN metastasis. However, multivariate analysis showed that ipsilateral central metastasis was an independent risk factor for lymph node metastasis in the contralateral central region when the number of ipsilateral central metas-tases is≥3 (P=0.010). Conclusion:Extracapsular invasion, prelaryngeal lymph nodes, and ipsilateral CLN influence the metastases of CLN. Bilateral CLN dissection should be performed when the number of ipsilateral central metastases is≥3 and there is merger of ex-tra-laryngeal lymph nodes or capsule invasion.

Objective To evaluate the clinical value of multi-slice spiral CT (MSCT)in the screening of coronary artery lesions in elderly patients with diabetes mellitus.Methods MSCT and coronary angiography(CAG)were performed in 136 elderly patients(68 patients with diabetes and 68 patients without diabetes).The number of diseased coronary segments and the plaque type (noncalcified,mixed and calcified)for each patient were determined.The characteristics of coronary lesions were compared between patients with and without diabetes.The sensitivity and specificity of MSCT were evaluated.Results More noncalcified and calcified plaques and few ermixed plaques were observed in patients with diabetes,compared with patients without diabetes(noncalcified plagues:10 cases or 14.7％ vs.4 cases or 5.9％;calcified plagues:47 cases or 69.1％ vs.39 cases or 57.4％)(P＜ 0.05).In addition,diabetic patients showed a significantly higher frequency of multivessel disease(P＜0.05).Furthermore,MSCT was able to clearly show stenosis and plaque type in the trunk and branches of the coronary artery,with a sensitivity of 91.0％,a specificity of 95.0％,a positive predictive value of 93％ and a negative predictive value of 96.0％.Conclusions Diabetes is associated with a higher risk of coronary artery disease.MSCT can effectively detect the characteristics of coronary artery disease in diabetic patients and is an effective,noninvasive,and safe screening method.

Objective To investigate the relationship between subgroups of central lymph node metastasis (sCLNM) and lateral lymph node metastasis (LNM) of unilatal papillary thyroid carcinoma (uPTC) with cervical lymph node negative(cN0).Methods The clinical and pathological data of 161 patients with cN0-uPTC who underwent total thyroidectomy+central lymph node dissection+lateral lymph node dissection from Jan.2016 to Dec.2016 were retrospectively analyzed.The relationship between the lymph node metastasis of each subarea in the central area of the affected side and the lymph node metastasis of the affected side was investigated.Results Binary logistic regression analysis of cN0-uPTC subregions in the affected central region showed:pre-laryngeal lymph node metastasis,pre-tracheal lymph node metastasis and paratracheal lymph node metastasis were independent risk factors for lymph node metastasis in the affected lateral region(P=0.008,0.016,0.035,respectively).Prelaryngeal lymph node metastasis was an independent risk factor for lymph node metastasis in the affected area Ⅱ (P=0.015).Pre-tracheal lymph node metastasis was an independent risk factor for lymph node metastasis in affected area Ⅲ (P=0.004).Pre-tracheal and para-tracheal lymph node metastasis were independent risk factors for lymph node metastasis in the affected Ⅳ area (P=0.035,0.011,respectively).Conclusions The lymph node metastasis pathway of thyroid cancer had certain regularity.The pre-laryngeal lymph node metastasis has the prediction value for the lymph node metastasis of the affected area Ⅱ.The pre-tracheal lymph node metastasis has the prediction value for the lymph node metastasis of the affected area Ⅲ.The pre-tracheal and paratracheal lymph node metastasis have the prediction value for lymph node metastasis of the affected area Ⅳ.Lymph node dissection in affected areas Ⅲ and Ⅳ needs to be considered in patients with pre-tracheal or paratracheal lymph node metastases.On this basis,lymph node dissection on the affected areas Ⅱ,Ⅲ,and Ⅳ might be considered if there is pre-laryngeal lymph node metastasis at the same time.