Treatment status of non-small cell lung cancer with METexon14 skipping mutation / 国际肿瘤学杂志

MET exon14 (METex14) skipping mutation is an independent driver gene in non-small cell lung cancer (NSCLC) . About 3%-4% of NSCLC patients carry METex14 skipping mutation. These patients have poor prognoses and poor responses to traditional chemotherapy and immunotherapy. Highly selective MET inhibitors such as capmatinib, tepotinib, savolitinib have shown good efficacy and safety data in clinical trials, which bring new treatment options for patients with METex14 skipping mutations.

Human Platelet-Rich Plasma-Derived Exosomes Promote the Proliferation of Schwann Cells Cultured in Vitro / 中国医学科学院学报

Objective To investigate the effect of human platelet-rich plasma-derived exosomes(PRP-exos)on the proliferation of Schwann cell(SC)cultured in vitro. Methods PRP-exos were extracted by polymerization-precipitation combined with ultracentrifugation.The morphology of PRP-exos was observed by transmission electron microscopy,and the concentration and particle size distribution of PRP-exos were determined by nanoparticle tracking analysis.Western blotting was employed to determine the expression of the marker proteins CD63,CD81,and CD9 on exosome surface and the platelet membrane glycoprotein CD41.The SCs of rats were isolated and cultured,and the expression of the SC marker S100β was detected by immunofluorescence staining.The fluorescently labeled PRP-exos were co-cultured with SCs in vitro for observation of their interaction.EdU assay was employed to detect the effect of PRP-exos on SC proliferation,and CCK-8 assay to detect the effects of PRP-exos at different concentrations(0,10,20,40,80,and 160 μg/ml)on SC proliferation. Results The extracted PRP-exos appeared as uniform saucer-shaped vesicles with the average particle size of(122.8±38.7)nm and the concentration of 3.5×1012 particles/ml.CD63,CD81,CD9,and CD41 were highly expressed on PRP-exos surface(P<0.001,P=0.025,P=0.004,and P=0.032).The isolated SCs expressed S100β,and PRP-exos could be taken up by SCs.PRP-exos of 40,80,and 160 μg/ml promoted the proliferation of SCs,and that of 40 μg/ml showed the best performance(all P<0.01). Conclusions High concentrations of PRP-exos can be extracted from PRP.PRP-exos can be taken up by SCs and promote the proliferation of SCs cultured in vitro.

Application of antibody-drug conjugates in the treatment of non-small cell lung cancer / 国际肿瘤学杂志

Antibody-drug conjugates (ADCs) have overcome the limitations of traditional chemotherapy and targeted therapy with unique advantage of antibody targeting, and made breakthrough achievements in the treatment of lung cancer. At present, the researches of ADCs in non-small cell lung cancer mainly involve HER2, HER3, TROP2, MET, CEACAM5. Many ADCs have passed rigorous clinical trials, and have shown good safety and efficacy, which provides theoretical basis for individualized treatment of lung cancer.

The role of RUNX1 in the apoptosis of epithelial cells in nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the expression of Runt-related transcription factor 1 (RUNX1) in nasal polyps (NPs) tissues and the potential role on apoptosis of primary human nasal epithelial cells (pHNECs) in NPs. Methods: The expression level of RUNX1 in NPs tissues was determined by Western blot (WB) and immunohistochemical staining (IHC). In vitro, TNF-α (20 ng/ml) was used to stimulate pHNECs to establish the apoptosis injury model. Hoechst staining was performed to observe pHNECs apoptosis by kit. Subsequently, quantitative real-time PCR (qRT-PCR) and WB were utilized to detect the expression of apoptosis-related proteins B-cell lymphoma-2 (BCL-2), BCL2-associated X (BAX) and cysteinyl aspartate specific proteinase-3 (Caspase-3) to assess the level of apoptosis. The plasmid of sh-RUNX1-6 was transfected into the pHNECs apoptosis model, then the effect of RUNX1 silence on apoptosis was evaluated by WB and flow cytometry. Statistical analysis was performed by the SPSS 19.0 and GraphPad Prism5 software. Results: The expression of RUNX1 in NPs tissue was significantly higher than that in inferior turbinates, and the difference was statistically significant (0.274±0.042 vs 0.110±0.027, t=9.675, P<0.05). Compared with the inferior turbinates, BAX and Caspase-3 expressions were increased whereas BCL-2 was decreased in NPs, and the differences were statistically significant (BAX 0.346±0.032 vs 0.302±0.037, Caspase-3 0.228±0.061 vs 0.158±0.065, BCL-2 0.090±0.047 vs 0.276±0.057, t value was 2.680, 2.361 and 7.575, respectively, all P<0.05). The expression levels of RUNX1 and apoptosis in pHNECs increased in a time-dependent manner after TNF-α exposure (P<0.05). Plasmid of sh-RUNX1-6 transfected silenced the expression of RUNX1 in pHNECs treated by TNF-α. After silencing RUNX1 in pHNECs apoptosis model, the protein levels of BAX and Caspase-3 were decreased, while the expression of BCL-2 was increased, the rate of apoptosis was decreased (P<0.05). Conclusions: RUNX1 is increased in NPs. Silencing RUNX1 can inhibit the apoptosis and reduce cell inflammatory damage of pHNECs induced by TNF-α.

Nociceptive behavioural assessments in mouse models of temporomandibular joint disorders / 国际口腔科学杂志·英文版

Orofacial pain or tenderness is a primary symptom associated with temporomandibular joint (TMJ) disorders (TMDs). To understand the pathological mechanisms underlying TMDs, several mouse models have been developed, including mechanical stimulus-induced TMD and genetic mouse models. However, a lack of feasible approaches for assessing TMD-related nociceptive behaviours in the orofacial region of mice has hindered the in-depth study of TMD-associated mechanisms. This study aimed to explore modifications of three existing methods to analyse nociceptive behaviours using two TMD mouse models: (1) mechanical allodynia was tested using von Frey filaments in the mouse TMJ region by placing mice in specially designed chambers; (2) bite force was measured using the Economical Load and Force (ELF) system; and (3) spontaneous feeding behaviour tests, including eating duration and frequency, were analysed using the Laboratory Animal Behaviour Observation Registration and Analysis System (LABORAS). We successfully assessed changes in nociceptive behaviours in two TMD mouse models, a unilateral anterior crossbite (UAC)-induced TMD mouse model and a β-catenin conditional activation mouse model. We found that the UAC model and β-catenin conditional activation mouse model were significantly associated with signs of increased mechanical allodynia, lower bite force, and decreased spontaneous feeding behaviour, indicating manifestations of TMD. These behavioural changes were consistent with the cartilage degradation phenotype observed in these mouse models. Our studies have shown reliable methods to analyse nociceptive behaviours in mice and may indicate that these methods are valid to assess signs of TMD in mice.

The prescribing cascade and medication therapy management between cholinesterase inhibitors and anticholinergic drugs / 中国药学杂志

OBJECTIVE: To discuss about one patient with Alzheimer′s disease and urinary incontinence and to investigate the prescribing cascade between cholinesterase inhibitors and anticholinergic drugs further more. METHODS: Clinical pharmacists participated in a medication therapy management program aiming at one patient with Alzheimer′s disease and urinary incontinence. By doing this they successfully identified and interrupted a prescribing cascade. Then some constructive advices were provided to doctors and patients on the rational administration of drugs. RESULTS: The drug treatment plan was adjusted by clinical pharmacists and doctors after evaluating the benefits and risks about the use of cholinesterase inhibitors and anticholinergic drugs in the elderly patient with chronic disease. And this change directly led to a significant relief of urinary incontinence in the patient. CONCLUSION: The use of cholinesterase inhibitors in Alzheimer′s patients increases the risk of urinary incontinence, and at the same time additional use of anticholinergic drugs in the treatment of urinary incontinence can further damage the cognition.Therefore, clinical pharmacists and doctors should pay great attention to the prescribing cascade of cholinesterase inhibitors and anticholinergic drugs. To identify and interrupt prescribing cascades is important when clinical pharmacists and doctors are prescribing prescriptions for elderly patients with chronic diseases. They must work closely for the optimization of prescriptions and the improvement of medication safety in elderly patients.

Identification of poliumoside metabolites in rat plasma, urine, bile, and intestinal bacteria with UPLC/Q-TOF-MS / 中国天然药物

Poliumoside is representative of phenylethanoid glycosides, which are widely found in many plants. Poliumoside is also regarded as the main active component of Callicarpa kwangtungensis Chun (CK), though its oral bioavailability in rat is extremely low (0.69%) and its in vivo and in vitro metabolism has not yet been systematically investigated. In the present study, an ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method was employed to identify the metabolites and investigate the metabolic pathways of poliumoside in rat after oral administration 1.5 g·kg of poliumoside. As a result, a total of 34 metabolites (30 from urine, 17 from plasma, and 4 from bile) and 9 possible metabolic pathways (rearrangment, reduction, hydration, hydrolyzation, dehydration, methylation, hydroxylation, acetylation, and sulfation) were proposed in vivo. The main metabolite, acteoside, was quantified after incubated with rat intestinal bacteria in vitro. In conclusion, the present study systematically explored the metabolites of poliumoside in vivo and in vitro, proposing metabolic pathways that may be significant for further metabolic studies of poliumoside.

Identification of poliumoside metabolites in rat plasma, urine, bile, and intestinal bacteria with UPLC/Q-TOF-MS / 中国天然药物

Poliumoside is representative of phenylethanoid glycosides, which are widely found in many plants. Poliumoside is also regarded as the main active component of Callicarpa kwangtungensis Chun (CK), though its oral bioavailability in rat is extremely low (0.69%) and its in vivo and in vitro metabolism has not yet been systematically investigated. In the present study, an ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method was employed to identify the metabolites and investigate the metabolic pathways of poliumoside in rat after oral administration 1.5 g·kg of poliumoside. As a result, a total of 34 metabolites (30 from urine, 17 from plasma, and 4 from bile) and 9 possible metabolic pathways (rearrangment, reduction, hydration, hydrolyzation, dehydration, methylation, hydroxylation, acetylation, and sulfation) were proposed in vivo. The main metabolite, acteoside, was quantified after incubated with rat intestinal bacteria in vitro. In conclusion, the present study systematically explored the metabolites of poliumoside in vivo and in vitro, proposing metabolic pathways that may be significant for further metabolic studies of poliumoside.

Progression of related diseases of desmoglein abnormal and pharmacological intervention / 中国药理学通报

Desmoglein,which is a kind of Ca2+ dependent desmosomal cadherins protein,is a major part of the desmosomes.The desmoglein that distributes in the epithelium,myocardium and other tissues plays a very important role in the cell junction.In recent years,the detection of the abnormal expression and function of the desmoglein was proved in many diseases,such as skin,mucous membrane and tumor related diseases.Drugs may have an important effect in the treatment of diseases by interfering with the expression and function of desmoglein.In this paper,the distribution of several subtypes of the family of desmosomes and their functions in the related diseases are reviewed,which may also provide some new clues for the new drug research on the target of desmogleins.

Regulatory Effect of Liuwei Dihuang Pills on Connexin 43 Expression in Hepatocarcinoma CBRH7919 Cells in Vitro / 广州中医药大学学报

Objective To investigate the effect of Liuwei Dihuang Pills (LDP)on the expression of connexin 43 (Cx43) in rat hepatocarcinoma CBRH7919 cells. Methods LDP-containing serum was prepared by serum pharmacological method. The protein expression of Cx43 in CBRH7919 cells was determined by Western blotting method, indirect immuno-fluorescent staining labeled by fluorescein isothiocyanate (FITC)-laser scanning confocal microscope technology and flow cytometry. And the mRNA expression of Cx43 in the hepatoma cells was detected by reverse transcription real-time quantitative polymerase chain reaction(RT-qPCR). Results Compared with the blank serum control group,the protein and mRNA expression levels of Cx43 were increased by volume fraction of 2.5%, 5%, 10% LDP-containing serum (P < 0.05 or P < 0.01). Conclusion LDP play an anti-cancer role through promoting the expression of Cx43 in CBRH7919 cells, altering Cx43 membrane location, and improving the gap junctional intercellular communication(GJIC).

Predictive value of ultrasonographic features in cervical lymph node metastasis of PTC / 医学研究生学报

Objective At present,the detection rate of cervical metastatic lymph nodes in patients with papillary thyroid carcinoma (PTC) is relatively low by imaging technology.The article aimed to demonstrate the ultrasonographic features of PTC in predicting cervical lymph nodes metastasis(CLNM).Methods A retrospective analysis was done on 169 PTC patients proved by surgery and pathology who underwent cervical lymph node dissection in the Department of Ultrasonography in Nanjing General Hospital of Nanjing Military Command from January 2016 to March 2017.The patients were divided into CLNM group(n=83) and non-CLNM group (n =86).Analysis was made on the related risk factors of PTC CLNM.Results Multivariate logistic regression analysis showed that age(OR=0.211,95％CI:0.078～0.571,P=0.002),nodule size (OR=3.116,95％CI:1.498～6.482,P=0.002) and shape (OR=3.000,95％CI:1.301～6.913,P=0.010) were risk factors for CLNM in PTC(P＜0.05).The sensitivity rates of patient's age,nodule shape,module size,and microcalcification for predicting CLNM in PTC patients were 91％、79％、61％、75％ respectively.Conclusion For PTC patients less than 30 years old,ultrasonographic features with maximal diameter of nodule ＞ 1 cm,irregular shape,and microcalcification have a certain predictive value on CLNM and can be used as the basis for the selection of intraoperative cervical lymph node dissection.

Risk Assessment of Echocardiography Parameter Scoring System for 1 Year Re-admission in Patients With Left Ventricular Systolic Dysfunction / 中国循环杂志

Objective: To establish an echocardiography parameter scoring system for assessing the risk of 1 year re-admission in patients with left ventricular systolic dysfunction (LVSD). Methods: A total of 412 chronic LVSD patients treated in our hospital from 2007-01 to 2016-01 were studied and the end point event was 1 year re-admission. The data included in 280 patients from 2007-01 to 2014-12 for establishing the scoring system and 132 patients from 2015-01 to 2016-01 for verifying the system. Based on 7 echocardiography parameters, the patients were divided into 7 sets of groups: ① Left ventricular diameter (LVD): Group0, n=290 and Group1, n=122;② Mitrial regurgitation (MR): Group0, n=203, Group1, n=138 and Group2, n=71; ③ Tricuspid regurgitation (TR): Group0, n=302, Group1, n=90 and Group2, n=20; ④ LVEF: Group0, n=272 and Group1, n=140; ⑤ Pulmonary artery systolic pressure: Group0, n=282 and Group1, n=130; ⑥ Hydropericardium: Group0, n=347 and Group1, n=65; ⑦ Hydrothorax:Group 0, n=261, Group1, n=86 and Group2, n=65. The parameters were identified by COX regression analysis, weighted value of scoring system was calculate by hazard ratio (HR), predictive value for1 year re-admission was assess by ROC curve and finally, scoring integration was verified by validation data group. Results: The integration score was calculated as follows: LVD>60mm=1 point; TR: Group1=1 point and Group2=3 points; MR: Group1=2 points and Group2=4 points; Hydrothorax: Group1=2 points and Group2=3 points;Hydropericardium=1 point. COX regression analysis indicated that for 1 year re-admission: HR=1.552 in Group1 vs Group0, HR=3.374 in Group2 vs Group0 and HR=4.562 in Group3 vs Group0, all P<0.05. The AUC of ROC for establishing the data was 70.0% (95% CI 0.640-0.761) and for verifying the data was 70.4% (95% CI 0.616-0.792); the best integration score was 4 points. Conclusion: Echocardiography parameter scoring system may better predict the risk of 1 year re-admission in LVSD patients which is superior to single echocardiography parameter.

Neoflavonoids and their pharmacological activities in Dalbergia genus / 中国中药杂志

Neoflavonoids are a kind of characteristic components in the Dalbergia genus. Based on the previous researches, 59 neoflavonoids have been obtained from the Dalbergia genus. According to their molecular skeleton, the neoflavonoids can be divided intodalbergiphenols, dalbergiones, dalbergins, benzophenones and other types. Modern research shows that neoflavonoids displayed a variety of pharmacological activities, such as anti-osteoporosis, anti-inflammatory, antitumor, anti-androgen, anti-allergic, antioxidation etc. This paper reviewed neoflavonoids and their pharmacological functions, which could provide the valuable reference for comprehensive utilization and new drug development in the Dalbergia genus.

Pharmacokinetics of mercury after oral administration of cinnabaris and Fufang Niuhuang Xiaoyan capsule in rats / 中国中药杂志

Fufang Niuhuang Xiaoyan capsule was a classical compound prescription with the efficacy of heat-clearing, detoxification, sedation and anti-inflammation, with cinnabaris as one of its active ingredients. The study focuses on the pharmacokinetics of mercury in rats after oral administration of cinnabaris and Fufang Niuhuang Xiaoyan capsule, in order to explore the effect of combined traditional Chinese medicines on mercury metabolism. In this study, the method of nitric-perchloric acid digestion system coupled with cold atomic-atomic fluorescence spectroscopy (CV-AFS) was adopted to accurately determine mercury in whole blood of rats. Fufang Niuhueng Xiaoyan capsule had three dose schemes of oral administration, namely equivalent clinical dose, 3 times of equivalent clinical dose and 10 times of equivalent clinical dose; And the doses of oral administration of cinnabaris was calculated according to that of Fufang Niuhuang Xiaoyan capsule. SPF grade healthy SD rats were fasted overnight before the oral administration with cinnabaris suspension (or Fufang Niuhuang Xiaoyan capsule suspension). After oral administration of different doses of cinnabaris, no obvious changes in tmax and MRT were observed, while Cmax/dose, AUC0-48 h/dose and AUC0-∞/dose decreased with the increase in dose, indicating that total mercury absorption in body was declining. As the dose increased, Ke, CL/F decreased, and t1/2 increased, indicating that the elimination slowed down, and mercury metabolism showed non-linear dynamic characteristics within a certain range of dose (22-220 mg•kg⁻¹). The total mercury metabolism in the whole blood of rats after oral administration with different doses of Fufang Niuhuang Xiaoyan capsule also showed non-linear dynamic characteristics. The results were correlated with the low solubility of cinnabaris in the body. Compared with cinnabaris, Fufang Niuhuang Xiaoyan capsule showed no obvious changes in V/F and MRT, while Ke, CL/F, tmax decreased, and t1/2, Cmax/dose, AUC0-48 h/dose, AUC0-∞/dose increased significantly. The results showed that Fufang Niuhuang Xiaoyan capsule accelerated absorption, slowed down elimination and improved the total absorption of mercury in the whole blood, indicating that Fufang Niuhuang Xiaoyan capsule may contain components for promoting absorption and alleviating elimination of mercury. Fufang Niuhuang Xiaoyan capsule had an impact on the pharmacokinetics of cinnabaris, and long-term administration of cinnabaris (Fufang Niuhuang Xiaoyan capsule) was possible to cause accumulation of mercury in the body. This study could explain changes in efficacy of Fufang Niuhuang Xiaoyan capsule, evaluate the rationality of compound medicines containing toxic elements and provide scientific basis for the rational and safe use of Fufang Niuhuang Xiaoyan capsule.

Protective effect of yixinshu capsule on myocardial ischemia reperfusion injury in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the protective effect of Yixinshu capsule on myocardial ischemia reperfusion injury (MIRI) in SD rats.</p><p><b>METHOD</b>Sixty healthy SD rats were randomized into six groups: sham group, MIRI model group, Xinsuning capsule group, low, middle or high dose Yixinshu capsule. Acute MIRI rat models were created by reperfusion for 120 min after anterior interventricular branch of the left coronary artery for 30 min. The serum creatine kinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST) and malondialdehyde(MDA), blood viscosity, and infarction area of myocardium were determined.</p><p><b>RESULT</b>Yixinshu capsule could reduce serum CK, LDH, AST and LDH activity, improve the blood viscosity, and reduced the myocardial infarct size.</p><p><b>CONCLUSION</b>Yixinshu capsule can protect against MIRI in rats.</p>

Effect of exclusive pregnancy food exchange method on pregnant women with abnormal glycometabolism / 中国医师进修杂志

Objective To observe the effect of exclusive pregnancy food exchange method on biochemical index and pregnancy outcome on pregnant women with abnormal glycometabolism,and evaluate its effectiveness on dietary guidance.Methods Sixty-seven pregnant women with abnormal glycometabolism who accepted physical examination and gave birth,were divided into traditional food exchange group (control group,33 cases) and exclusive pregnancy food exchange group (observation group,34 cases),and were given respective intervention until the childbirth.The blood biochemical indexes and the pregnancy outcome between two groups were compared.Results Fasting blood glucose (FBG),2 h postprandial blood glucose (PBG),glycosylated hemoglobin (HbA1c) and triglyeride (TG) in observation group after treatment were significantly lower than those before treatment (P ＜ 0.05 or ＜ 0.01).PBG,HbA1c and TG in control group alter treatment were significantly lower than those before treatment (P ＜ 0.01).After treatment,PBG,HbA1c and TG in observation group were significantly lower than those in control group (P＜ 0.01),after 3 months follow-up,differences still existed (P ＜ 0.01).The total incidence of pregnant women complications in observation group was much lower than that in control group [14.71％(5/34) vs.36.36％(12/33),P ＜ 0.05],there was no significant difference between two groups on neonatal complications (P ＞ 0.05).Conclusions Exclusive pregnancy food exchange method can improve pregnant glycometabolism and lipid metabolism of pregnant women with abnormal glycometabolism,and reduce the incidence of pregnant women and infant adverse pregnancy outcome.It is great worthy to popularize and apply in dietary guidelines.

A new 3, 4-seco-lanostane triterpenoid from a marine-derived fungus Ascotricha sp. ZJ-M-5 / 药学学报

To study the secondary metabolites of a marine-derived fungus Ascotricha sp. ZJ-M-5, several chromatographic methods including macroporous resin, silica gel, ODS and Sephadex LH-20 were used to isolate the compounds, and their structures were elucidated on the basis of physicochemical properties and spectroscopic methods. Ten compounds were obtained and identified as ascotrichic acid B (1), (3R)-6-hydroxymellein (2), beta-carboline (3), (22E, 24R)-ergosta-7, 22-diene-3beta, 5alpha, 6beta-triol (4), (22E, 24R)-ergosta-7, 22-diene-3beta, 5alpha, 6beta, 9alpha-tetraol (5), cyclo (Leu-Pro) (6), cyclo (Ile-Leu) (7), cyclo (Pro-Val) (8), cyclo (Pro-Gly) (9), and cyclo (Hpro-Ala) (10). Among them, compound 1 is a new 3, 4-seco-lanostane triterpenoid which has been isolated from the filamentous fungi for the first time, and compounds 2-10 are firstly isolated from Ascotricha genus.

In vitro dissolution of forsythin in Forsythia suspensa powder of different particle diameter / 中国中药杂志

<p><b>OBJECTIVE</b>To examine the in vitro dissolution of forsythin in Forsythia suspensa powder of different particle diameter, in order to give guidance to the grinding process.</p><p><b>METHOD</b>HPLC was used to determine the in vitro dissolution quantity and dissolution velocity of forsythin coarse powder, fine powder and ultramicroscopic powder.</p><p><b>RESULT</b>The dissolution curves of Forsythia suspensa coarse powder, fine powder and ultramicroscopic powder were basically inconformity to Weibull distribution. Specifically, T50 was 11.8, 10.5 and 6.8 min, respectively, and Q45 was 78.22%, 81.91% and 90.76%, respectively.</p><p><b>CONCLUSION</b>The superfine milling process can significantly increase the dissolution quantity and dissolution velocity of forsythin.</p>

Enzyme kinetics and molecular modeling studies of G6PDMahidol associated with acute hemolytic anemia.

G6PDMahidol enzyme is the most common variant in the Achang Chinese ethnic group and clinically manifests as class II. In this study, G6PDMahidol enzyme was characterized by molecular modeling to understand its kinetics. G6PDMahidol, G6PDG487A and G6PDWT proteins were heterologously expressed in the G6PD-deficient DF213 E. coli strain, purified and their steady-state kinetic parameters were determined. Compared with G6PDWT, the Km and Vmax of NADP+ with G6PDG487A were about 28-fold and 12-fold lower, respectively. The Ki values of dehydroepiandrosterone (DHEA), NADPH and ATP with G6PDG487A showed 29.5-fold, 2.36-fold reduction and 1.83-fold increase, respectively. A molecular modeling of G6PDG487A was performed based on the X-ray structure of human G6PD (PDB: 2BH9). It is suggested that Ser-163 might affect the stability of G6PDG487A -helix d and -strand E, besides the conformation of -strand D. In conclusion, the biochemical and structural properties of G6PDG487A and G6PDWT enzymes are significantly different, which may be responsible for clinical diversity of G6PD deficiencies.

Survivin antisense oligodeoxynucleotides inhibits the proliferation of hepatocellular carcinoma cells and enhances 5-FU sensitivity / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the inhibitory effect of survivin antisense oligodeoxynuleotides (ASODN) mediated by polyethylenimine (PEI) on hepatocelluar carcinoma SMMC-7721 cell proliferation and its effect on chemosensitivity to 5-FU in tumor-bearing mice.</p><p><b>METHODS</b>The inhibitory effect of PEI-ASODN on SMMC-7721 cell proliferation was assayed by WST-8 test, Trypan blue exclusion test, and cell clone formation assay. In mouse models of transplanted H22 cell hepatocarcinoma and ascites tumor, the effect of 5-FU combined with PEI-ASODN on the weight and volume of the subcutaneous tumors was examined. The tumor inhibition rate in the tumor-bearing mice was calculated and the average survival time recorded.</p><p><b>RESULTS</b>SMMC-7721 cells incubated with different concentrations of PEI-ASODN for 48 h showed significantly reduced cell proliferation in comparison with the control cells, while PEI or ASODN alone produced no such inhibitory effect. Incubation of SMMC-7721 cells with 0.75 micromol/L PEI-ASODN for 24, 48, 72, and 96 h resulted in significantly suppressed cell proliferation, and a 7-day incubation of the cells with PEI-ASODN at different concentrations (0.25-0.75 micromol/L) significantly inhibited the cell clone formation. In the tumor-bearing mice, the tumor weight and volume were obviously reduced with a tumor inhibition rate of 56.91% and volume inhibition rate of 57.83%, significantly different from those in saline-treated mice (P<0.01). In the mice bearing ascites tumor, the average survival time was 22.0 days in saline group and 42.7 days in 5-FU+PEI-ASODN treatment group, showing a a life-prolonging rate of 94.09% in the latter group. A synergetic effect was noted between 5-FU and PEI-ASODN.</p><p><b>CONCLUSION</b>PEI-ASODN complex can significantly inhibit the proliferation of hepatocarcinoma SMMC-7721 cells and enhance 5-FU chemosensitivity of the tumor cells in vitro and transplanted H22 tumors in mice.</p>