Objective·To investigate the association of insulin resistance with left ventricular(LV)remodeling after ST-segment elevation myocardial infarction(STEMI)in patients without a history of diabetes mellitus.Methods·This study consecutively enrolled STEMI patients without a history of diabetes mellitus who underwent percutaneous coronary intervention in the Department of Cardiology of Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,from January 2014 to December 2022.The patients were followed up for 6 months.Age,gender,smoking status,blood pressure,body mass index,biochemical indexes(liver function,kidney function,lipid profiles,glycemic levels and peak troponin levels,etc.)and pharmacological treatment were recorded.Homeostasis model assessment of insulin resistance(HOMA-IR)was used to evaluate insulin resistance and mean values of visit-to-visit HOMA-IR were calculated.Patients were divided into 4 groups(low-level group,low-to-medium-level group,medium-to-high-level group,and high-level group)according to the quartiles of mean HOMA-IR levels.Echocardiography was performed at baseline and during follow-up.Then the association between mean values of insulin resistance and post-infarction LV remodeling was analyzed.Results·A total of 219 patients were finally included,with an average age of(62.7±11.9)years,and male patients accounted for 85.4％(187 cases).The average follow-up time was(6.4±1.8)months.During follow-up,the average number of HOMA-IR measurements was(4.32±2.18),and the mean value of visit-to-visit HOMA-IR was 2.41(1.58,3.98),which was higher than normal range.The results showed that post-infarction LV end-diastolic diameter(P=0.027)and LV end-diastolic volume index(P=0.013)generally showed a trend for dilation with increasing mean HOMA-IR levels.Pearson correlation analysis revealed the mean values of visit-to-visit HOMA-IR were positively correlated to changes in LV dimensions(△ LV end-diastolic volume index:r=0.20,P=0.003;△ LV end-diastolic diameter:r=0.21,P=0.002).Multivariate regression analysis demonstrated that higher HOMA-IR was independently associated with greater LV dilation after STEMI,even after adjusting for age,gender,traditional risk factors(history of hypertension,body mass index,smoking status,renal function and lipid profiles),pharmacological treatment,baseline LV ejection fraction and peak troponin levels.Compared with patients with the lowest quartile of HOMA-IR,those with the highest HOMA-IR quartile exhibited a 7.727 mL/m2 increase in LV end-diastolic volume index(P＜0.001).Conclusion·This study reveals that insulin resistance is prevalent in STEMI patients without a history of diabetes mellitus.Insulin resistance is an independent predictor of adverse LV remodeling in this population.

Objective·To investigate the association of insulin resistance with left ventricular(LV)remodeling after ST-segment elevation myocardial infarction(STEMI)in patients without a history of diabetes mellitus.Methods·This study consecutively enrolled STEMI patients without a history of diabetes mellitus who underwent percutaneous coronary intervention in the Department of Cardiology of Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,from January 2014 to December 2022.The patients were followed up for 6 months.Age,gender,smoking status,blood pressure,body mass index,biochemical indexes(liver function,kidney function,lipid profiles,glycemic levels and peak troponin levels,etc.)and pharmacological treatment were recorded.Homeostasis model assessment of insulin resistance(HOMA-IR)was used to evaluate insulin resistance and mean values of visit-to-visit HOMA-IR were calculated.Patients were divided into 4 groups(low-level group,low-to-medium-level group,medium-to-high-level group,and high-level group)according to the quartiles of mean HOMA-IR levels.Echocardiography was performed at baseline and during follow-up.Then the association between mean values of insulin resistance and post-infarction LV remodeling was analyzed.Results·A total of 219 patients were finally included,with an average age of(62.7±11.9)years,and male patients accounted for 85.4％(187 cases).The average follow-up time was(6.4±1.8)months.During follow-up,the average number of HOMA-IR measurements was(4.32±2.18),and the mean value of visit-to-visit HOMA-IR was 2.41(1.58,3.98),which was higher than normal range.The results showed that post-infarction LV end-diastolic diameter(P=0.027)and LV end-diastolic volume index(P=0.013)generally showed a trend for dilation with increasing mean HOMA-IR levels.Pearson correlation analysis revealed the mean values of visit-to-visit HOMA-IR were positively correlated to changes in LV dimensions(△ LV end-diastolic volume index:r=0.20,P=0.003;△ LV end-diastolic diameter:r=0.21,P=0.002).Multivariate regression analysis demonstrated that higher HOMA-IR was independently associated with greater LV dilation after STEMI,even after adjusting for age,gender,traditional risk factors(history of hypertension,body mass index,smoking status,renal function and lipid profiles),pharmacological treatment,baseline LV ejection fraction and peak troponin levels.Compared with patients with the lowest quartile of HOMA-IR,those with the highest HOMA-IR quartile exhibited a 7.727 mL/m2 increase in LV end-diastolic volume index(P＜0.001).Conclusion·This study reveals that insulin resistance is prevalent in STEMI patients without a history of diabetes mellitus.Insulin resistance is an independent predictor of adverse LV remodeling in this population.

Adverse drug reactions are often encountered in the process of medication and are quite troublesome for clinicians. Skin is one of the most frequently affected organs by adverse drug reactions. Adverse drug reactions involving skin are called "drug-induced dermatitis" or "drug eruption". In some rare instances, drug eruption can be severe and life-threatening which is known as severe cutaneous adverse drug reaction. However, due to the mixed use of drugs, it is difficult to identify the culprit drug, which makes multiple drugs needed to be avoided. Recently, many studies have found that HLA alleles are closely related to the certain culprit drug. HLA genotyping before administration can significantly reduce the incidence of severe cutaneous adverse drug reaction related to certain drugs. Since limited HLA alleles are found, HLA genotyping can only prevent adverse drug reaction to a limited extent. At present, drug provocation tests are regarded as the "gold standard" to identify the culprit drug. However, this diagnostic program has not been widely developed because of the high risk. In addition, a variety of in vivo and in vitro diagnostic methods (including drug patch test, drug skin test, drug specific IgE test, basophil activation test, lymphocyte transformation test, et al) also provide evidences to identify the culprit drug.

Adverse drug reactions are often encountered in the process of medication and are quite troublesome for clinicians. Skin is one of the most frequently affected organs by adverse drug reactions. Adverse drug reactions involving skin are called "drug-induced dermatitis" or "drug eruption". In some rare instances, drug eruption can be severe and life-threatening which is known as severe cutaneous adverse drug reaction. However, due to the mixed use of drugs, it is difficult to identify the culprit drug, which makes multiple drugs needed to be avoided. Recently, many studies have found that HLA alleles are closely related to the certain culprit drug. HLA genotyping before administration can significantly reduce the incidence of severe cutaneous adverse drug reaction related to certain drugs. Since limited HLA alleles are found, HLA genotyping can only prevent adverse drug reaction to a limited extent. At present, drug provocation tests are regarded as the "gold standard" to identify the culprit drug. However, this diagnostic program has not been widely developed because of the high risk. In addition, a variety of in vivo and in vitro diagnostic methods (including drug patch test, drug skin test, drug specific IgE test, basophil activation test, lymphocyte transformation test, et al) also provide evidences to identify the culprit drug.

OBJECTIVESHeparin-binding neurite-promoting factor (HBNF) is a heparin-binding protein primarily found in the brain, which can stimulate neurite outgrowth in vitro. We expressed recombinant human heparin-binding neurite-promoting factor (hrHBNF) using a yeast system, and observed its activity in stimulating neurite outgrowth in vitro.

METHODScDNA encoding mature human HBNF was amplified from total RNA isolated from an 18-week aborted human fetal brain by RT-PCR method. After amplification, the HBNF cDNA gene was cloned into pPIC9K, a shuttle expression vector for yeast system. The positive clone of expression vector bearing HBNF cDNA gene was obtained by screening. Verified recombinant vector was then used to transform Pichia strain GS115 by electroporation. His(+) transformants were selected on minimal dextrose medium (MD) plates which were histidine free. His(+) yeast recombinants with multi-copy inserts were screened in vivo by their resistance to G418. PCR analysis was used to confirm the integration of the HBNF cDNA gene into the Pichia genome. Secreted expression of hrHBNF protein in culture medium was obtained when the positive clone containing the HBNF cDNA gene was induced by methanol. The hrHBNF product purified by gel chromatography was added to cultured rat pheochromocytoma (PC12) cells to observe its ability to stimulate neurite outgrowth.

RESULTSIn the recombinant expression vector, the insert was sequenced to show exactly the sequence encoding human HBNF according to Genbank data. The HBNF cDNA gene was cloned downstream to the alpha-factor, and its open reading frame was in frame with the alpha-factor signal sequence in pPIC9K. SDS-PAGE showed that the molecular weight of the induced expression product was about 18 kDa, consistent with that of human HBNF reported in the literature. The protein product did promote neurite outgrowth in cultured rat pheochromocytoma (PC12) cells.

CONCLUSIONRecombinant human heparin-binding neurite-promoting factor can be expressed with a yeast system, and its product possesses the biological activity to promote neurite outgrowth.

Animals ; Base Sequence ; Carrier Proteins ; biosynthesis ; genetics ; pharmacology ; Cytokines ; biosynthesis ; genetics ; pharmacology ; DNA, Complementary ; chemistry ; Genetic Vectors ; Humans ; Molecular Sequence Data ; Neurites ; drug effects ; physiology ; PC12 Cells ; Pichia ; genetics ; Rats ; Recombinant Proteins ; biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction

Purpose To purify recombinant angiogenesis inhibitor r-K4K5 and investigate its inhibitoryeffects on bovine capillary endothelial (BCE) cell proliferation, chick embryo chorioallantoic membrane(CAM) angiogenesis and growth of experimental human non-small cell lung cancer (adeno). Methodsr-K4K5 was obtained by salting out and gel filtration with the purity of 95% determined by SDS-PAGE.BCE cells were cultured with DMEM media containing r-K4K5. The cells were counted in 24,48,72 hrespectively. r-K4K5 was injected daily into all 7-day chick embryo CAMs and CAM angiogenesis wasobserved at 72 h after incubation. The Balb/c (nu/nu) mice implanted with human SPC-Al tumor pieceswere grown for 10 days and then randomly divided into three groups. One group was treated with PBS, theother two groups were treated with local subcutaneous injection of purified r-K4K5 at 8 μg and 80 μg lpermouse every other day. They were daily observed and sacrificed in 14 days. Each tumor was weighed.Results The number of BCE cells, blood vessels diameter less than 50 μn of chick embryo CAM and theaverage weight of experimental tumor were decreased markedly in all the groups treated with r-K4K5.Conclusions r-K4K5 inhibits proliferation of BCE cells, angiogenesis of chick embryo CAMs and thegrowth of experimental human SPC-A1 non small lung cancer (adeno).

ObjectiveTo explore the inhibitory effects of r-k4k5 on retinal neovascularization.MethodsEighty-eight one-week-old C57BL/6J mice were put into the environment with 75% oxygen for 5 days to establish models of vascular proliferation retinopathy. One eye of each mouse received an intravitreal injection of 500 ng of r-k4k5 (large-dosage group) and of 250 ng of r-k4k5(small-dosage group), and the same volume of BSS was injected into the other eye of the mice both in these two groups as a control. The ADPase histochemical staining was used for retinal flatmount to observe changes of retinal vessels. The inhibitory effects of r-k4k5 on retinal neovascularization were evaluated by counting the endotheliocyte nuclei of new vessels extending from retina to vitreous in the tissue-slice.ResultsRegular distributions and reduced density of retinal blood vessels in eyes in the treatment group were found in retinal flatmount. The number of the endotheliocyte nuclei of new vessels extending from retina to vitreous was less in the eyes in the treatment group than which in control group (P