The development of small-molecule inhibitors targeting MYC / 药学学报

The MYC gene, one of the most common dysregulated driver genes in human cancers, is composed of three paralogous genes C-MYC, N-MYC and L-MYC. It is abnormally activated in more than half of cancer types. Since MYC plays an important role in the formation, maintenance and progression of cancer, targeting MYC is an effective strategy for cancer treatment. As a potential anti-cancer target, MYC is considered "undruggable" because it lacks a suitable pocket for accommodating small molecule inhibitors. Recently, under the guidance of protein structure information and many computational tools, many indirect strategies to inhibit MYC have emerged and shown favorable anti-cancer effects in tumor models. In this paper, the recent small molecules that indirectly target MYC are divided into inhibitors acting on the protein-protein interaction (PPI) among MYC and other proteins, and targeting inhibitors regulating MYC action. Additionally, the introduction and assessment towards compounds with different mechanisms are summarized to provide reference for the further research of MYC inhibitors.

Effects of TAT-SOD at Acupoints on Essential Hypertension by Monitoring Meridians Electrical Potential / 中国结合医学杂志

OBJECTIVES@#To investigate the effect on essential hypertension of the topical application of TAT-Cu, Zn-superoxide dismutase (TAT-SOD) at left acupoint Zusanli (ST 36), and to observe whether the change of electrical potential difference (EPD) can be related to the change of blood pressure.@*METHODS@#Sixteen patients with essential hypertension and 16 healthy subjects were included in the study. EPD between the left acupoints of Yanglingquan (GB 34) and Qiuxu (GB 40) was firstly screened out for the EPD detection. An intracellular superoxide quenching enzyme, TAT-SOD, was topically applied to the acupoint ST 36 within an area of 1 cm once a day, and the influence on EPD was investigated. The dosage applied to TAT-SOD group (n=8) was 0.2 mL of 3000 U/mL TAT-SOD cream prepared by adding purified TAT-SOD to a vehicle cream, while placebo group (n=8) used the vehicle cream instead. The left acupoints of Yanglingquan (GB 34) and Qiuxu (GB 40) were selected for EPD measurement after comparing EPD readings between 5 acupoints on each of all 12 meridians.@*RESULTS@#EPDs between the left acupoints of GB 34 and GB 40 for 16 patients of essential hypertension and 16 healthy subjects were 44.9±6.4 and 5.6±0.9 mV, respectively. Daily application of TAT-SOD for 15 days at ST 36 of essential hypertension patients significantly decreased systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 179.6 and 81.5 mm Hg to 153.1 and 74.1 mm Hg, respectively. Responding to the change in blood pressure, EPD between the left acupoints of GB 34 and GB 40 also declined from 44.4 to 22.8 mV with the same trend. No change was observed with SBP, DBP and EPD between the left acupoints of GB 34 and GB 40 with the daily application of the placebo cream.@*CONCLUSION@#Enzymatic scavenging of the intracellular superoxide at ST 36 proved to be effective in decreasing SBP and DBP. The results reconfirm the involvement of superoxide anions and its transportation along the meridians, and demonstrate that EPD between acupoints may be an indicator to reflect its functioning status. Moreover, preliminary results suggest a close correlation between EPD and blood pressure readings, implying a possibility of using EPD as a sensitive parameter for blood pressure and to monitor the effect of antihypertensive treatment.

The development of small-molecule inhibitors that target PRC2-related proteins / 药学学报

Abnormal expression of polycomb repressive complex 2 (PRC2) is related to the development of a variety of diseases. Inhibition of normal or overactive PRC2 can reduce cell survival and inhibit tumor growth in several cancers. Therefore, the identification and development of small molecule inhibitors has become an active field of current epigenetic-related anti-tumor strategies. A small molecule inhibitor targeting the S-adenosyl-L-methionine (SAM) binding site of enhancer of zeste homologue 2 (EZH2) has been approved by FDA. However, acquired drug resistance is of concern. Drugs targeting two different binding sites of embryonic ectoderm development (EED) are also being developed. The development of EZH2-EED proton pump inhibitor has attracted extensive attention due to its unique mechanism of action. In this paper, we review the research progress on various small molecule inhibitors that target PRC2-related proteins to provide a basis for further research and development of related drugs.

Role of TXNIP-mediated oxidative stress in delaying Alzheimer's disease by estrogen / 中南大学学报(医学版)

To study the functional mechanism of thioredoxin-interacting protein (TXNIP) in delaying Alzheimer's disease (AD) by estrogen.
 Methods: After estradiol (E2) treatment in Aβ-induced AD cell model, reactive oxygen species (ROS), TXNIP, and apoptosis levels were detected. After lentiviral infection with TXNIP overexpression, the effect of E2 on ROS and apoptosis were observed. In the AD rat model, the learning and memory ability and the expression of TXNIP in the hippocampus were observed in the presence of E2. After overexpressing TXNIP, the effect of E2 on the learning and memory ability of AD rat model was observed.
 Results: ROS, TXNIP and apoptosis levels were enhanced in AD cell model, while E2 treatment reduced ROS, TXNIP and apoptosis levels in AD cell model. After enhancing TXNIP, E2 treatment reduced ROS and apoptosis levels in AD cell model. Similar to the cell experiment, E2 enhanced the learning and memory ability in the AD rat model and inhibited the expression of TXNIP in brain, while TXNIP overexpression attenuated the effect of E2 on learning and memory ability in the AD rats.
 Conclusion: Estrogen can inhibit the expression of TXNIP in nerve tissue, reduce nerve damage, and delay the development of AD.

Therapeutic Effect of Nerve Growth Factor Thermosensitive Gel on Sciatic Nerve Injury of Rats / 中国实验方剂学杂志

Objective: To prepare nerve growth factor(NGF) temperature sensitive in situ gel and investigate its therapeutic effect on sciatic nerve injury of rats.Method: NGF thermosensitive gel was prepared and its prescription was optimized by central composite design-response surface methodology.Fifty rats were randomly divided into the normal group,model group,NGF injection group(10 mg·L-1),NGF low-dose(10 mg·L-1) and high-dose(20 mg·L-1) thermosensitive gel groups,and sciatic nerve injury model of rats was established.The effect of NGF thermosensitive gel on the injury of sciatic nerve were comprehensively examined by taking rat behavior,sciatic nerve function index(SFI),time of withdrawal reflex,wet weight ratio of gastrocnemius muscle,and histomorphological changes as indicators.Result: The gelation temperature of NGF thermosensitive gel was 35.2℃ after the formulation being optimized,which was in line with the standard for injection.Four-eight weeks after operation,the SFI and wet weight ratio of gastrocnemius muscle in rats of NGF high-dose thermosensitive gel group were significantly higher than those in the model group and NGF injection group,but its time of withdrawal reflex was significantly lower than those in the model group and NGF injection group,and the effect was in a dose-dependent manner.Arrangement of regenerated nerve fibers in sciatic nerve injury area of rats from NGF high-dose thermosensitive gel group was more tidy,dense and continuous than that of the model group.Conclusion: NGF thermosensitive gel can promote repair of sciatic nerve injury in rats.

Influence of varying intensities of water-jet force on autologous fat draft viability: an in-vitro study / 中华医学美学美容杂志

Objective To observe the effect of varying intensities of water-jet force on autologous fat graft viability.Methods Lipoaspirate was taken from 12 female patients undergoing waterjet assisted abdominal liposuction at our department.According to the intensity of water-jet force,the experimental group was divided into four subgroups:R1 (pressure,30 bar),R2 (pressure,50 bar),R3 (pressure,70 bar) and R4 (pressure,90 bar).Hand-held suction was taken as the control group C.Adipose tissue was filtered with cotton cushion and centrifuged at low speed,and the composition ratio of water and fat tissue from each group was observed.Calcein-AM/Hoechst 33342 staining was used to detect the viability of adipocytes.Results Fat aspirates was divided into four layers:oil layer,pure fat tissue,liquid and bottom sediment.Oil ratios of R1,R2,R3,R4 and C were (8.9 ± 2.3) ％,(9.6±2.1)％,(10.3±1.3)％,(14.2±1.6)％ and (9.5±1.8)％,respectively.There was no statistically significant difference between R1,R2,R3 and C (P＞0.05).Statistically significant difference was found between R4 and other groups (P＜0.001).Viability of adipocytes from R1,R2,R3,R4 and C groups were (88.1±2.8)％,(89.9±1.9)％,(84.8±2.3)％,(78.0±1.7)％ and (91.1±2.9)％ respectively.There was no statistically significant difference between R1,R2 and C (P＞ 0.05).Statistically significant difference was found between R3,R4 and C (P ＜ 0.05).Conclusions Viability of fat graft harvested under lower intensity of water-jet force (R1,R2) is higher than that harvested under higher intensity of water-jet force (R3,R4).

The free anterolateral thigh flap with KISS technique for reconstruction of the scalp defect / 中华整形外科杂志

Objective@#To report the effect of the free anterolateral thigh flap with KISS technique in reconstruction of scalp defect.@*Methods@#11 patients with scalp tumor were treated with radical resection and free transfer of the anterolateral thigh flap with KISS technique from March 2016 to June 2017. The flap was designed carrying two skin pedals according to preoperative detection of perforators, then the flap was dissected to carry one main pedicle or two different pedicles, after that two skin pedals were assembled with the KISS technique to cover the wound.@*Results@#No total failure of flap was observed. No donor-site complication was observed. The contour of reconstructed scalp was satisfactory.@*Conclusions@#The free anterolateral thigh flap with KISS technique is reliable in reconstruction of scalp defect. It features low donor site morbidity, high reconstructive efficiency and reliable perfusion.

Scutellaria barbata flavonoids inhibits NFT aggregation and regulatory mechanism in rats induced by composited Aβ / 中国病理生理杂志

AIM: To investigate the effects of Scutellaria barbata flavonoids (SBF) on neurofibrillary tangle (NFT) aggregation, tau protein phosphorylation and the regulated mechanism of glycogen synthase kinase (GSK) 3βand protein phosphatase (PP) 2A in the rats induced by amyloid βprotein 25-35 (Aβ25-35) in combination with AlCl3 and re-combinant human transforming growth factor ( RHTGF)-β1( composited Aβ) .METHODS:The male SD rats were used to establish the simulated Alzheimer disease ( AD) model by intracerebroventricular injection of composited Aβ.The Morris water maze was applied for screening the successful model rats with learning and memory deficits .The successful model rats were daily and orally administrated with SBF at doses of 35, 70 and 140 mg/kg or positive control drug Ginkgo biloba leaves flavonoids ( GLF) at 140 mg/kg for 37 d.The silver nitrate staining was used to determine the cortical NFT .The protein levels of total tau, phosphorylated protein of tau at Ser199 and Ser214 sites, GSK3βand PP2A in hippocampus and cortex were determined by Western blot .The mRNA expression of GSK3βand PP2A in the hippocampus and cortex was detected by RT-PCR.RESULTS:Compared with sham group , the cell number of positive NFT with silver nitrate staining in model rat cerebral cortex was significantly increased .The protein levels of phosphorylated tau protein at Ser 199 and Ser214 sites, GSK3βin the hippocampus and cerebral cortex in the model rats dramatically elevated , and PP2A was marked decreased as compared with the sham group rats.Meanwhile, the mRNA expression of GSK-3βsignificantly increased but PP2A was de-creased.However, these above abnormalities were differently attenuated by treating with SBF at different doses or GLF at 140 mg/kg for 37 d.CONCLUSION: SBF suppresses the NFT aggregation by inhibition of the regulatory functions of GSK-3βand PP2A, thus reducing the phosphorylation of tau protein .

Effect of fluoride concentration on the corrosion behavior of cobalt-chromium alloy fabricated by two different technology processes / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aims to determine the effect of fluoride concentration on the corrosion behavior of cobalt-chromium alloy fabricated by two different technology processes in a simulated oral environment.</p><p><b>METHODS</b>A total of 15 specimens were employed with selective laser melting (SLM) and another 15 for traditional casting (Cast) in cobalt-chromium alloy powders and blocks with the same material composition. The corrosion behavior of the specimens was studied by potentiodynamic polarization test under different oral environments with varying solubilities of fluorine (0, 0.05%, and 0.20% for each) in acid artificial saliva (pH = 5.0). The specimens were soaked in fluorine for 24 h, and the surface microstructure was observed under a field emission scanning electron microscope after immersing the specimens in the test solution at constant temperature.</p><p><b>RESULTS</b>The corrosion potential (Ecorr) value of the cobalt-chromium alloy cast decreased with increasing fluoride concentration in acidic artificial saliva. The Ecorr, Icorr, and Rp values of the cobalt-chromium alloy fabricated by two different technology processes changed significantly when the fluoride concentration was 0.20% (P < 0.05). The Ecorr, Icorr, and Rp values of the cobalt-chromium alloy fabricated by two different technology processes exhibited a statistically significant difference. The Icorr value of the cobalt-chromium alloy cast was higher than that in the SLM group cobalt-chromium alloy when the fluoride concentration was 0.20% (P < 0.05). The Ecorr, tRp alues of the cobalt-chromium alloy cast were lower htan those of the SLM group cobalt-chromium alloy when the fluoride concentration was 0.20% (P< 0 .05).</p><p><b>CONCLUSION</b>Fluoride ions adversely affected the corrosion resistance of the cobalt-chromium alloy fabricated by two different technology processes. The corrosion resistance of the cobalt-chromium alloy cast was worse than that of the SLM group cobalt-chromium alloy when the fluoride concentration was 0.20%.</p>

Interaction of polymorphisms of PPAR-γ2 gene -C34G and NADPH oxidase subunit p22phox gene -C242T with Helicobacter pylori infection in esophageal squamous cell carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the interaction of polymorphisms of PPAR-γ2 gene -C34G and NADPH oxidase subunit p22phox gene -C242T with helicobacter pylori (H. pylori) infection in esophageal squamous cell carcinoma (ESCC) .</p><p><b>METHODS</b>A total of 200 cases of LSCC of Broder grade I, 200 of Broder grade II and of grade III were enrolled in this study with 200 healthy individuals as the control group. The genetic polymorphisms of PPAR-γ2 gene -C34G and NADPH oxidase subunit p22phox gene -C242T were analyzed using PCR-RFLP in peripheral blood leukocytes.C-urea breath test (C-UBT) was used to testC disntegration per minute (DPM) for evaluating the infection status of H. pylori. An unconditional logistic regression model was used to analyze the interaction of nucleotide polymorphisms and H. pylori infection.</p><p><b>RESULTS</b>The risk of ESCC significantly increased in subjects with -C34G (CG), -C34G(GG), -C242T (CT), and -C242T (TT) genotypes. Combined analysis of the polymorphisms showed that the subjects carrying -C34G (GG)/ -C242T (TT) had a high risk of ESCC, and a positive interaction was found between -C34G (GG) and -C242T (TT) in increasing the risk of ESCC. Positive interactions in the pathogenesis of ESCC were also found between -C34G (CG) and -C242T (TT), between -C34G (CG) and -C242T (CT), and between -C34G (GG) and -C242T (CT) (γ>1). The risk of ESCC significantly increased in subjects with H. pylori infection, which showed positive interactions with -C34G (CG), -C34G (GG), -C242T (CT) and -C242T (TT) in increasing the risk of ESCC (γ>1).</p><p><b>CONCLUSION</b>Individuals carrying -C34G(CG), -C34G(GG), -C242T (CT) and -C242T (TT) genotypes have a high risk of developing ESCC, and these genotypes interact with H. pylori infection in the pathogenesis of LSCC, suggesting the importance of eradicating H. pylori for prevention of ESCC.</p>

Interaction of Polymorphisms of Resistin Gene Promoter -420C/G, Glutathione Peroxidase -1 Gene Pro198Leu and Cigarette Smoking in Nonalcoholic Fatty Liver Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Many studies have suggested that cigarette smoking and polymorphisms of resistin and glutathione peroxidase-1 (GPx-1) genes are closely correlated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, few reports have investigated these associations with respect to NAFLD susceptibility. We, therefore, examined the distribution of polymorphisms in GPx-1 and resistin genes in NAFLD patients and healthy controls and analyzed the relationship between these polymorphisms and smoking status.</p><p><b>METHODS</b>Nine hundred NAFLD patients and 900 healthy controls were selected, and the genetic polymorphisms of resistin gene promoter-420C/G and GPx-1 gene Pro198Leu were analyzed by polymorphism-polymerase chain reaction (PCR) in DNA extracted from peripheral blood leukocytes. Interactions between the two mutants and the gene-environment interaction with cigarette smoking were also analyzed.</p><p><b>RESULTS</b>Genotype frequencies of -420C/G (GG) and Pro198Leu (LL) were significantly higher in NAFLD cases (49.56% and 50.11%, respectively) compared with healthy controls (23.67% and 24.22%, respectively) (P = 0.0069; P = 0.0072). Moreover, the risk of NAFLD with -420C/G (GG) was significantly higher than in controls (odds ratio [OR] =3.1685, 95% confidence interval (CI) =1.9366-5.2073). Individuals carrying Pro198Leu (LL) had a high risk of NAFLD (OR = 3.1424, 95% CI = 1.7951-5.2367). Combined analysis of the polymorphisms showed that the -420C/G (GG)/Pro198Leu (LL) genotype was significantly more common in the NAFLD group than in the control group (39.44% vs. 12.78%, respectively, P = 0.0054), while individuals with -420C/G (GG)/Pro198Leu (LL) had a high risk of NAFLD (OR = 5.0357, 95% CI = 3.1852-7.8106). Moreover, the cigarette smoking rate in the NAFLD group was significantly higher than in the control group (OR = 1.8990, P = 0.0083 in the smoking index (SI) ≤400 subgroup; OR = 5.0937, P = 0.0051 in the SI >400 subgroup), and statistical analysis suggested a positive interaction between cigarette smoking and -420C/G (GG) (γ = 5.6018 in the SI ≤400 subgroup; γ = 4.4770 in the SI >400 subgroup) and Pro198Leu (LL) (γ = 5.7715 in the SI ≤400 subgroup; γ = 4.5985 in the SI >400 subgroup) in increasing the risk of NAFLD.</p><p><b>CONCLUSION</b>NAFLD risk factors include -420C/G (GG), Pro198Leu (LL) and cigarette smoking, and these three factors have a significant additive effect on NAFLD risk.</p>

Dalitong granule combined with electroacupuncture in the treatment of functional dyspepsia: A randomized controlled trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore clinical short and long-term effect of combining dalitong granule (DG) and electroacupuncture group (EA) in the treatment of functional dyspepsia.</p><p><b>METHODS</b>Totally 640 patients with confirmed functional dyspepsia were randomly divided into 4 groups using a randomized digital table: the DG group, the EA group, the combined group and the control group, 160 cases in each group. The DG group was treated with 6 g DG 3 times daily; the EA group was treated with puncture of points Zusanli (ST36), Zhongwan (CV12), Neiguan (PC6), Taichong (LR3) and Gongsun (SP4) twice daily; the combined group with above-mentioned DG and EA; and the control group with 5 mg mosapride 3 times, 20 mg pantoprazole and 25 mg amitriptylines twice daily. The treatment course was 4 weeks for all groups. The symptom score, quality of life score by Short Form 36 Health Survey Questionnaires (SF-36), plasma motilin by radioimmunoassay, electrogastrographic frequencies by electrogastrogram (EGG) and gastric emptying by B-sonography were examined, and adverse reactions were observed before, at the end of treatment and 60 weeks post-treatment.</p><p><b>RESULTS</b>In the DG group 1 case dropped out for not taking medicine strictly and 1 case was lost to follow-up, while 1 case in the EA group and 2 cases in the combined therapy group were lost to follow-up. Compared with pre-treatment, quality of life score, plasma motilin, electrogastrographic frequencies and gastric emptying were all increased significantly, while symptom score was decreased significantly at the end of treatment in each group (P<0.01); in the combined group quality of life score, plasma motilin, electrogastrographic frequencies and gastric emptying were all significantly higher than those in the other groups, while symptom score was significantly lower than in the other groups (P<0.05). Compared with at the end of treatment, these indices changed insignificantly in the combined group and the EA group 60 weeks post-treatment (P>0.05), but the 4 increased indices were all decreased significantly, and symptom score was increased significantly in the DG and the control groups (P>0.05). The short and long-term total effective rates in the combined group were all significantly higher than those in the other treatment groups (P<0.05 or P<0.01). No serious adverse reaction occurred in the four groups.</p><p><b>CONCLUSION</b>Combined treatment of DG and EA could increase both plasma motilin and electrogastrographic frequencies, promote gastric emptying, alleviate the symptom of dyspepsia so as to increase quality of life, with better safety and long-term effect.</p>

Interaction between the polymorphisms of cyclooxygenase-2-1195G/A,MnSOD9Ala/val genes and the high-fat diets and its correlation with ulcerative colitis / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the interaction of the polymorphisms of cyclooxygenase-2-1195G/A (COX-2-1195G/A) and manganese superoxide dismutase 9Ala/Val (MnSOD9Ala/Val) genes and the high-fat diets and its potential correlation with ulcerative colitis (UC).</p><p><b>METHODS</b>The genetic polymorphisms of COX-2-1195G/A and MnSOD9Ala/Val were analyzed by polymorphism-polymerase chain reaction (PCR) in peripheral blood leukocytes obtained from 750 UC patients (UC group) and 750 healthy subjects (control group).</p><p><b>RESULTS</b>The frequencies of COX-2-1195G/A(A/A) and MnSOD9Ala/Val(V/V) were 49.07% and 50.13% in UC group and 21.20% and 22.40% in control group, respectively (P<0.01). The risk of UC significantly increased in subjects with COX-2-1195G/A(A/A) genotype (OR=3.5808,95%CI=1.8062-5.3478) and in those with MnSOD9Ala/Val(V/V) genotype(OR=3.4828,95%CI=1.9137-5.5496). Pooled analysis of the polymorphisms showed that distribution frequency of COX-2-1195G/A(A/A)/MnSOD9Ala/Val (V/V) was 40.67% in UC group and 8.40% in control group (P<0.01). Subjects with COX-2-1195G/A(A/A)/MnSOD9Ala/Val(V/V) had a significantly higher risk of UC (OR=7.5655,95% CI=4.1849-11.2037). The rate of high-fat diets was significantly higher in the UC group than in the control group(49.73 vs.20.13%,P<0.01),and statistic analysis suggested an interaction between high-fat diet and COX-2-1195G/A(A/A)(Γ=11.81821)and MnSOD9Ala/Val (V/V)(Γ=9.0107), which increase risk of UC.</p><p><b>CONCLUSIONS</b>COX-2-1195G/A(A/A),MnSOD9Ala/Val (V/V), and high-fat diet are the risk factors of UC. The interaction between the genetic polymorphisms of COX-2-1195G/A and MnSOD9Ala/Val and the high-fat diet increases the risk of UC.</p>

Preparation and properties of chitosan/β-glycerophosphate thermosensitive hydrogel containing amino-carbon nanotubes / 中国药学杂志

OBJECTIVE: To synthesis chitosan/β-glycerophosphate (CS/β-GP) thermosensitive hydrogel containing multi-walled carbon nanotubes-polyethyleneimine (MWCNTs-PEI) complexes and to lay a foundation for further research of dual slow-release delivery system. METHODS: Chitosan thermosensitive hydrogel containing MWCNTs-PEI was prepared by MWCNTs-PEI dispersed to the chitosan thermosensitive hydrogel. As the indicator of the gelling time, the experiment studied the effect of β-GP concentration, pH, temperature and MWCNTs-PEI composite quality on the thermosensitive chitosan hydrogel, and then it was charactered by using transmission electron microscopy (SEM), infrared spectrometer(IR), and initially investigated in vivo compatibility. RESULTS: The dynamic rheology method investigated the gelling temperature were about 37.0°C. Within a certain range, the gelling time of thermosensitive chitosan hydrogel was shortened with the increase of concentration of β-GP, pH, temperature, and the quality of MWCNTs-PEI complexes, and they could be transformed into the hydrogel in vivo. The addition of MWCNTs-PEI complex didn't react chemically with the thermosensitive chitosan hydrogel and significantly make the holes of the chitosan thermosensitive hydrogel smaller by SEM and FT-IR, eventually leading to the swelling rate and the corrosional ratio decrease. CONCLUSION: Chitosan/β-glycerophosphate thermosensitive hydrogel containing amino-carbon nanotubes has a rapid gelation and good temperature-sensitivity, which can serve as a good double sustained-release carrier.

Correlations between polymorphisms of extracellular superoxide dismutase, aldehyde dehydrogenase-2 genes, as well as drinking behavior and pancreatic cancer / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the correlation between drinking behavior combined with polymorphisms of extracellular superoxide dismutase (EC-SOD) and aldehyde dehydrogenase-2 (ALDH2) genes and pancreatic cancer.</p><p><b>METHODS</b>The genetic polymorphisms of EC-SOD and ALDH2 were analyzed by polymerase chain reaction restriction fragment length polymorphism in the peripheral blood leukocytes obtained from 680 pancreatic cancer cases and 680 non-cancer controls. Subsequently the frequency of genotype was compared between the pancreatic cancer patients and the healthy controls.The relationship of drinking with pancreatic cancer was analyzed.</p><p><b>RESULTS</b>The frequencies of EC-SOD (C/G) and ALDH2 variant genotypes were 37.35% and 68.82% respectively in the pancreatic cancer cases, and were significantly higher than those in the healthy controls (21.03% and 44.56%, all P<0.01). People who carried EC-SOD (C/G) (OR=2.24, 95% CI= 1.81-4.03, P<0.01) or ALDH2 variant genotypes (OR=2.75, 95% CI=1.92-4.47, P<0.01) had a high risk to develop pancreatic cancer. Those who carried EC-SOD (C/G) genotype combined with ALDH2 variant genotype had a high risk for pancreatic cancer (29.56% vs. 6.76%, OR=7.69, 95% CI=3.58-10.51, P<0.01). The drinking rate of the pancreatic cancer group (64.12%) was significantly higher than that of the control group (40.15%; OR=2.66, 95% CI=1.30-4.42, P<0.01). An interaction between drinking and EC-SOD (C/G)/ALDH2 variant genotypes increased the risk of occurrence of pancreatic cancer (OR=25.00, 95% CI= 11.87-35.64, P<0.01).</p><p><b>CONCLUSION</b>EC-SOD (C/G), ALDH2 variant genotypes and drinking might be the risk factors of pancreatic cancer.</p>

Preparation of multi-walled carbon nanotubes-polyethyleneimine composite and its cytotoxicity on PC12 cells / 中国药学杂志

OBJECTIVE: To synthesize water-soluble multi-walled carbon nanotubes-polyethyleneimine (MWCNTs-PEI) composite with low cytotoxicity and to lay a foundation for further research of loading drugs with carbon nanotubes. METHODS: MWCNTs-PEI composite was prepared by modifying carboxylated multi-walled carbon nanotubes(MWCNTs-COOH) with polyethylene (PEI), and then the composite was characterized by transmission electron microscopy, infrared spectra, UV spectra and thermalgravimetric analysis. The cytotoxicity of the composite on PC12 cells was measured by methyl thiazolyl tetrazolium(MTT) assay to preliminarily evaluate its biocompatibility. RESULTS: The dissolubilities of MWCNTs-PEI and MWCNTs-COOH complexes were respectively 1.009 and 0.0601 mg · mL-1, and the former was about 16 times of the latter. The cytotoxicity of MWCNTs-PEI composite on PC 12 cells was significantly milder than that of MWCNTs-COOH composite as indicated by MTT assay (P < 0.05). CONCLUSION: MWCNTs-PEI composite not only improves the dispersibility of carbon nanotubes, but also reduces its in vitro cell toxicity.

Effect of LY294002 on protein kinase B activation in human lens epithelial cell / 中华实验眼科杂志

Background Protein kinase B (Akt) is the center of multiple cellular signaling pathways,and it participates in the regulation of cell function,such as proliferation,migration,and metabolism of cells.Phosphoinositide 3-kinase (PI3K) promotes activation of Akt and therefore triggers many signal pathways.PI3K inhibitor can silent Akt,but whether it can affect the biological behavior of lens epithelial cells (LECs) during the posterior capsular opacity (PCO) is worthy of investigation.Objective This study was to explore the effect of LY294002,a PI3K inhibitor,on Akt activation in human LECs.Methods Human LECs strain,HLEC-B3 cells,were cultured and passaged.The cells were incubated to 96-well plate for 24 hours,then LY294002 was added with the final concentration at 0,10,20,30,40,50,60,70,80 μmol/L,respectively.After incubation for 24 hours,cell counting kit-8 (CCK-8) was used to detect the inhibitory rate of cell proliferation.Transforming growth factor-β2 (TGF-β2) of 10 μg/L was added in the medium of cells as TGF-β2 group,TGF-β2 + LY294002 (20 μmol/L) was used to coculture the other group of cells,and the cells without TGF-β2 and LY294002 served as the control group.Phosphorylation of Akt (p-Akt) in the cells was detected by laser scan confocal immunofluorescence microscope.The expression level of p-Akt was evaluated using Western blot.Results CCK-8 assay showed that the A value of the cells was gradually reduced with the increase of LY294002 concentration (Fgroup =9.72,P =0.00),but the A value was significant raised along with the lapse of time (Ftime =1737.54,P=0.00).Confocal immunofluorescence revealed that a little of p-Akt was expressed in the control cells.After induced by TGF-β2,lots of red fluorescence of p-Akt was seen in cells around the cell membranes.But in the TGF-β2+LY294002 co-culture cells,the fluorescence of Akt was much weaker.Western blot showed that the expression level of p-Akt was 0.91±0.08,1.48±0.13 and 0.95±0.19 in the control group,TGF-β2 group and TGF-β2 +LY294002 group,respectively,with a significant difference among the three groups (F =15.04,P =0.00).Conclusions LY294002 can inhibit the activation of Akt induced by TGF-β2.LY294002 may have utility in the prevention and treatment of PCO.

Expression of focal adhesion kinase in human lens epithelial cells induced by hydrogen peroxide / 中华实验眼科杂志

Background The pathogenesis of age-related cataract is associated with the apoptosis of lens epithelial cells (LECs) caused by oxidative stress.Previous studies showed that intracellular focal adhesion kinase (FAK) pathway can be activated by H2O2 in vitro,which induced apoptosis of cells.To investigate the effect of oxidative on FAK expression in LECs is one of important studies in the prevention of age-related cataract.Objective This study was to investigate the expression and function of FAK in human LECs treated by H2O2.Methods Human LECs strain (HLECs-B3) were cultured in vitro in the low glucose DMEM with 10％ fetal bovine serum.Different concentrations (0,30,50,70,100,300,500,700,1000 μmol/L) of H2O2 were added into the culture medium for 24 hours.The survival rate of the cells was detected by Cell Counting Kit-8 (CCK-8) assay.Cell morphology as well as the expression and distribution of FAK in the cells were observed by immunofluorescent staining under the laser confocal microscope.Apoptosis was observed by hoechst33258 staining,and Western blot assay was used to quantitatively detect the expression and phosphorylation of FAK.Results The survival rate of the cells was (1.00±0.03) ％,(1.24±0.03)％,(1.36±0.24) ％,(0.93±0.02)％,(1.75±0.19)％,(1.37±0.18) ％,(0.64±0.01)％,(0.59±0.11)％,(0.14±0.05)％ in 0,30,50,70,100,300,500,700,1000 μmol/L H2O2 groups,with a significant difference among them (F =95.30,P =0.00).The survival rates of the cells in the below 300 μmol/L H2O2 groups were significantly higher than those in the 0 μmol/L H2O2 group,and survival rates of the cells in the above 500 μmol/L H2O2 groups were significantly lower than those in the 0 μmol/L H2O2 group(all at P＜0.05).After H2 O2 treatment for 24 hours,HLECs-B3 cells transformed from polygon shape to spindle shape and extended pseudopodiums,meanwhile the green fluorescence for FAK exhibited in the cytoplasm.Cell apoptosis was found in the 1000 μ mol/L H2O2 group.Western blot assay revealed that the expressing levels (grey scale) were significantly different among the various groups (F=28.08,P=0.00),and FAK expressing levels in the below 300 μmol/L H2O2 groups were significantly higher than those of the 0 μmol/L H2O2 group; while the expressing levels in the above 500 μmol/L H2O2 groups were lower than those of the control 0 μmol/L H202 group (all at P＜0.05).After treated by different concentrations of H2O2,the phosphorylation level of intracellular FAK (p-FAK) was significantly higher in 3 hours group than that in 30 minutes group (all at P＜0.05).Conclusions H2 O2 can affect the survival,proliferation and morphology of human LECs by activating the intracellular FAK pathway,indicating that FAK may play roles in the regulation process of cell biological behavior.

Single-incision versus conventional laparoscopic cholecystectomy: a meta-analysis / 中华外科杂志

<p><b>OBJECTIVE</b>To study feasibility and security of single-incision laparoscopic cholecystectomy (SILC).</p><p><b>METHODS</b>Clinical trials comparing SILC with conventional laparoscopic cholecystectomy (LC) for benign gallbladder disease published from 2010 to 2012 were retrieved. A meta-analysis was conducted to evaluate operative time, blood loss, conversion rate, post-operative pain, wound satisfaction score, post-operative hospital stay and post-operative complications between SILC group and LC group. A fixed effect model or random effect model was established to collect the data.</p><p><b>RESULTS</b>Eleven random clinical trials on 859 patients qualified for the meta-analysis, 449 patients being allocated to SILC and 410 patients to LC. There was no significant difference between SILC group and LC group for blood loss, conversion rate, post-operative pain, post-operative hospital stay and post-operative complications. However, operative time was significantly longer in SILC group than LC group (IV = 16.66, 95%CI: 9.60 - 23.72, Z = 4.62, P = 0.00). Furthermore, wound satisfaction score was significantly higher in SILC group than in LC group (IV = 0.95, 95%CI: 0.56 - 1.34, Z = 4.76, P = 0.00).</p><p><b>CONCLUSIONS</b>SILC may be superior to LC in terms of cosmetic outcome, but not in operative time. Currently, SILC is a safe procedure for proper patients in experienced surgeons.</p>

Modified reduction mammoplasty with central pedicle-double circle technique / 中华医学美学美容杂志

Objective To review the clinical data of reduction mammoplasty by central pedicle technique,and to summarize all kinds of the complications to modify the technique for improvement of long term aesthetic effects.Methods The postoperative complications were analyzd and then an approach was used to investigate the pattern of the blood supply and the nerve distribution of breast.Based on the anatomical study,a modified double-circle reduction mammoplasty technique was designed to treat patients with hypertrophical breasts. Results With a follow-up for 3 months to 3 years,the patients who underwent this modified central pedicle technique,had an invisible scar,good projection,the better shape of breast and preserved their sensation of nipple-areola complex.Conclusions Modified central pedicle technique is a safe and reliable technique,especially ideal for Chinese women.The blood supply is rich and the sensation of nipple-areola complex is preserved.The fixation of the gland tissue is more important than the dermal-bra.