Protective Effects of Trimetazidine on Bone Marrow Mesenchymal Stem Cells Viability in an ex vivo Model of Hypoxia and in vivo Model of Locally Myocardial Ischemia

Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury,but this approach is limited by their poor viability after transplantation.The present study was to investigate whether trimetazidine (TMZ) could improve survival of MSCs in an ex vitro model of hypoxia,as well as survival,differentiation,and subsequent activities of transplanted MSCs in rat hearts with acute myocardial infarction (AMI).MSCs at passage 3 were examined for their viability and apoptosis under a transmission electron microscope,and by using flow cytometry following culture in serumfree medium and exposure to hypoxia (5% CO2,95% N2) for 12 h with or without TMZ.Thirty Wistar rats were divided into 3 groups (n=10 each group),including groupⅠ(AMI control),groupⅡ (MSCs transplantation alone),and group Ⅲ (TMZ+MSCs).Rat MSCs (4×107) were injected into peri-infarct myocardium (MSCs group and TMZ+MSCs group) 30 min after coronary artery ligation.The rats in TMZ+MSCs group were additionally fed on TMZ (2.08 mg?kg-1?day-1) from day 3 before AMI to day 28 after AMI.Cardiac structure and function were assessed by echocardiography at 28th day after transplantation.Blood samples were collected before the start of TMZ therapy (baseline),and 24 and 48 h after AMI,and inflammatory cytokines (CRP,TNF-α) were measured.Then the sur-vival and differentiation of transplanted cells in vivo were detected by immunofluorescent staining.The cellular apoptosis in the peri-infarct region was detected by using TUNEL assay.Furthermore,apoptosis-related proteins (Bcl-2,Bax) within the post-infarcted myocardium were detected by using Western blotting.In hypoxic culture,the TMZ-treated MSCs displayed a two-fold decrease in apoptosis under serumfree medium and hypoxia environment.In vivo,cardiac infarct size was significantly reduced,and cardiac function significantly improved in MSCs and TMZ+MSCs groups as compared with those in the AMI control group.Combined treatment of TMZ with MSCs implantation demonstrated further decreased MSCs apoptosis,further increased MSCs viability,further decreased infarct size,and further improved cardiac function as compared with MSCs alone.The baseline levels of inflammatory cyto-kines (CRP,TNF-α) had no significant difference among the groups.In contrast,all parameters at 24 h were lower in TMZ+MSCs group than those in MSCs group.Furthermore,Western blotting indicated that the expression of antiapoptotic protein Bcl-2 was upregulated,while the proapoptotic protein Bax was down-regulated in the TMZ+MSCs group,compared with that in the MSCs group.It is suggested that implantation of MSCs combined with TMZ treatment is superior to MSCs monotherapy for MSCs viability and cardiac function recovery.

Effect of ligand troglitazone on peroxisome proliferator-activated receptor γ expression and cellular growth in human colon cancer cells

AIM： To investigate the effect of troglitazone on peroxisome proliferator-activated receptor γ （PPARγ） expression and cellular growth in human colon cancer HCT-116 and HCT-15 cells and to explore the related molecular mechanism.METHODS： Human colon cancer HCT-116 and HCT-15 cells cultured in vitro were treated with troglitazone. Reverse transcription-polymerase chain reaction （RT-PCR） and Western blot were employed to detect the effect of troglitazone on PPARy expression. The proliferative activity was determined by MTT assay, cell cycle and apoptosis were detected by flow cytometry. Apoptosisrelated genes, cell cycle regulatory genes and p53 were examined by RT-PCR and Western blot respectively. RESULTS： The expression of PPARy in colon cancer HCT-116 and HCT-15 cells was up-regulated by troglitazone. Troglitazone inhibited proliferation, induced apoptosis and cell cycle G1 arrest in colon cancer cells. Troglitazone induced p53 expression in HCT-116 cells, but not in HCT-15 cells. The down-regulation of survivin and bcl-2 was found in both cell lines and up-regulation of bax was found only in HCT-116 cells, being consistent with growth inhibition in HCT-116 cells but not in HCT-15 cells. Troglitazone increased expression of p21^WAF1/CIP1 （p21）, p27^KIP1 （p27） and reduced cyclin D1 in HCT-116 cells while only a minor decrease of cyclin D1 was found in HCT-15 cells. CONCLUSION： Troglitazone is an inductor of PPARγ in colon cancer cells and inhibits PPARγ-dependently proliferation, which may attribute to cell cycle G1 arrest and apoptosis in colon cancer cells. Troglitazone may induce p53-independent apoptosis and p53- dependent expression of p21 and p27. Depending on cell background, different activation pathways may exist in colon cancer cells.

Effects of Atractylodes Macrocephala on the Cytomembrane Ca^(2+)-activated K^+ Currents in Cells of Human Pregnant Myometrial Smooth Muscles

The study examined the inhibitory effect of Atractylodes macrocephala （AM） on the uterine contraction during premature delivery and explored its electrophysiological mechanism by studying the effects of AM on the Ca^2＋-activated K^＋ currents of pregnant human myometrial smooth muscle cells with or without the treatment with intedeukin-6. Single cells were acutely isolated from pregnant human myometrial smooth muscles. Whole-cell Ca^2＋-activated K^＋ currents were recorded by using an Axopatchl-D amplifier. The cells were divided into three groups： group A in which AM was added into perfusate, group B, in which interleukin-6 was added into perfusate） and group C in which AM was added into perfusate after addition of interleukin-6. IL-6 10 ng/mL inhibited BKca by 36.9%±13.7% as compared with control （P〈0.01）. AM at 2 mg/mL raised BKca by 36.7%±22.6% or 45.2%±13.7% with or without the treatment of IL-6, respectively （P〈0.01）. It is concluded that AM was able to enhance the BKca of pregnant human myometrial smooth muscle cells treated or untreated with interleukin-6 and its effect on the BKca IL-treated cells was stronger that its effect on BKca of untreated cells. Our results suggested that AM can help to maintain the membrane potentials and the resting status of pregnant human myometrial smooth muscle cells.

Carboxypeptidase A6 Promotes the Proliferation and Migration of Hepatocellular Carcinoma by Up-regulating AKT Signaling Pathway

Summary:Hepatocellular carcinoma(HCC)has a poor treatment prognosis and high mortality worldwide.Understanding the molecular mechanism underlying HCC development would benefit the identification of diagnostic biomarkers and the improvement of the treatment strategies.The expression of carboxypeptidase A6(CPA6)has been reported in epilepsy and febrile seizures rather than in any type of cancers.However,the function of CPA6 expression in HCC is not yet understood.In this study,we aimed to investigate the clinicopathological significance of the expression of CPA6 in HCC and the underlying mechanisms.We observed that the expression of the CPA6 protein was increased significantly in HCC tissues than in paracancerous tissues.To explore its function in HCC,both gain-and loss-of-function studies demonstrated that CPA6 played a vital role in promoting HCC growth and metastasis.When knocking down CPA6 with shRNA,HCC cell proliferation and migration could be suppressed.Meanwhile,CPA6 overexpression could promote proliferation and migration of HLF cells.Moreover,CPA6 could activate AKT serine/threonine kinase(AKT)signaling pathway as confirmed by Western blotting.In conclusion,our study revealed that CPA6 could promote HCC cell proliferation and migration via AKT-mediated signaling pathway.These findings suggest that CPA6 is a promising diagnostic biomarker and therapeutic target to improve the prognosis of HCC.

APPLICATION OF ACUPUNCTURE ANESTHESIA TO APPENDECTOMY AND COMMENTS ON THE OPERATION AND ITS POSSIBLE MECHANISMS

Objectives: To observe the analgesic effect and to analyze the related mechanisms of acupuncture anesthesia (AA) for appendectomy. Methods: A total of 41 cases of appendicitis patients (24 males and 17 females) were subjected into this observation. Electroacupuncture (AA, 60-100 Hz, a bearable stimulus strength) of Pishu (BL 20), Weishu (BL 21), Zhangmen (LR 13) and Wushu (GB 27) was performed beginning 30 minutes before operation. Adjuvants used were luminal (100 mg, intra muscular injection), dolantin (1 mg/kg), 0.5% procaine (1-2 mL). Results: Of the 41 cases, the successful rate was 87.80% and the excellent plus good rate was 75.61% respectively. Conclusion: Acupuncture anesthesia is applicable for appendectomy in clinic but is still to be improved further in operation.

Electric stimulation at sciatic nerve evokes long-term potentiation of cornu dorsale medullae spinalis field potential in rats at various developmental phases

BACKGROUND： Long-term potentiation of cornu dorsale medullae spinalis field potential in adult rats has already been reported; however, there is lack of correlated researches on naenonate, infant and adult rats which have different responses to pain conduction information.OBJECTIVE： To observe the various effects of electric stimulation at sciatic nerve on long-term potentiation of evoked field potential at superficial layer of cornu dorsale medullae spinalis of rats at various developmental phases and analyze manifestations of pain conduction information at superficial layers （ Ⅰ - Ⅱ）of cornu dorsale medullae spinalis in immature rats.DESIGN： Grouping controlled study.SETTING： Department of Physiology, Medical College of Wuhan University.MATERIALS： The experiment was carried out in the Laboratory of Physiology （provincial laboratory）,Medical College of Wuhan University from March 2006 to May 2007. A total of 27 healthy male Sprague-Dawley （SD） rats, 17- 90 days old, SPF grade, weighing 41 -200 g, were provided by Experimental Animal Center, Medical College of Wuhan University.METHODS： Based on their birthdays, rats were divided into naenonate group （17 - 20 days old, weighing 41-52 g, n =10）, infant group （35 - 50 days old, weighing 87 - 125 g, n =10） and adult group （60 - 90 days old, weighing 180 -200 g, n =7）. Left sciatic nerve was separated and stimulated with single square wave （15 V, 0.5 ms）. Meanwhile, evoked field potential was recorded at superficial layers of lateral T13 - L1 cornu dorsale medullae spinalis and then stimulated with high-frequent and high-intensive tetanizing current （30 -40 V, 0.5 ms, 100 Hz, 1s per bundle, 10s in bundle interval） four times. After the operation, onset of long-term potentiation was observed; meanwhile, amplitude changes and latency of field potential were analyzed.MAIN OUTCOME MEASURES： Amplitude and latency changes of field potential at superficial layers of cornu dorsale medullae spinalis of rats in the three groups.RESULTS： A total of 27 accepted rats were involved in the final analysis. ① Amplitude changes： Electric stimulation at sciatic nerve with high-frequent and high-intensive tetanizing current could induce evoked field potential at superficial layers （Ⅰ-Ⅱ ） of cornu dorsale medullae spinalis in the three groups.Long-term potentiation in the naenonate group manifested that amplitude of A-kind never fiber was raised and there was significant difference （P〈0.05）. In addition, average amplitude was increased and there was obviously significant difference （P〈0.01）. Long-term potentiation in the infant group manifested that amplitude of C-kind never fiber was raised and there was significant difference （P〈0.01）; while, long-term potentiation in the adult group manifested that amplitude of C-kind never fiber was raised and there was significant difference （P〈0.01）. Otherwise, latencies in the three groups were all shortened. ② Latency changes： Average latency of A-kind nerve fiber in the naenonate group was shortened and there was significant difference （P〈0.01）; in addition, evoked potential of C-kind nerve fiber was low and latency was immovable. There was no significant difference before and after high-frequent and high-intensive electric stimulation （P〉0.05）. Average latency of C-kind nerve fiber in the infant group was shortened and there was significant difference （P〈0.01）; in addition, evoked potential of A-kind nerve fiber was stable and latency was immovable. There was no significant difference before and after high-frequent and high-intensive electric stimulation （P〉0.05）. Average latency of C-kind nerve fiber in the adult group was shortened and there was significant difference （P〈0.01）; in addition, evoked potential of A-kind nerve fiber was stable and latency was immovable. There was no significant difference before and after high-frequent and high-intensive electric stimulation.CONCLUSION： Evoked field potential at superficial layer of comu dorsale medullae spinalis can be recorded through electric stimulation at sciatic nerve. Single stimulation and tetanizing electric stimulation can cause different characteristics of evoked field potential in rats at various developmental phases.Superficial layer of cornu dorsale medullae spinalis of naenonate rats is mainly caused by A-kind nerve fiber which participants in pain conduction and formation of pain sensitivity; however, that of infant and adult rats mainly depends on C-kind nerve fiber.

Effects of Isoflurane on the Actions of Neuromuscular Blockers on the Muscle Nicotine Acetylcholine Receptors

Summary: In this study, we tested the hypothesis that volatile anesthetic enhancement of muscle relaxation is the result of combined drug effects on the nicotinic acetylcholine receptors. The poly A m RNA from muscle by isolation were microinjected into Xenopus oocytes for receptor expression. Concentration-effect curves for the inhibition of Ach-induced currents were established for vecuronium, rocuranium, and isoflurane. Subsequently, inhibitory effects of NDMRs were studied in the presence of the isoflurane at a concentration equivalent to half the concentration producing a 50 % inhibition alone. All tested drugs produced rapid and readily reversible concentration-dependent inhibition. The 50 % inhibitory concentration values were 889 μmol/L (95 % CI: 711-1214 μmol), 33.4 μmol (95 % CI: 27.1-41.7 nmol) and 9.2 nmol (95 % CI: 7.9-12.3 nmol) for isoflurane, rocuranium and vecuronium, respectively. Coapplication of isoflurane significantly enhanced the inhibitory effects of rocuranium and vecuronium, and it was especially so at low concentration of NMDRs. Isoflurane increases the potency of NDMRs, possibly by enhancing antagonist affinity at the receptor site.

High-performance Liquid Chromatographic Determination of Urinary Trans,Trans-Muconic Acid Excreted by Workers Occupationally Exposed to Benzene

Objective To investigate the relationship between trans, trans-muconic acid （ttMA） as benzene metabolite of occupational workers and benzene concentration in air. Methods A rapid and sensitive high-performance liquid chromatography was developed to determine the level of urinary ttMA. ttMA was extrated from urinary samples in liquid-liquid phase a ODS （2） （5u） column （Ф4.6 min× 150 mm） and detected at wavelength 264 nm in a UV detector using vanillic acid as an internal standard. The mobile phase was acetaticacid/tetrahydrofuran/methanol/water （v/v, 1：2：10：87）. The method was validated with 56 urine samples collected from occupationally benzene-exposed individuals. Results A correlation coefficient （r = 0.9963 ） was found for ttMA ranging 0.10-10.00 μg/mL. The limit of detection was 0.10μ g/mL. The recovery and reproducibility were generally over 90%. There was a positive correlation between ttMA and benzene level in air. The equation was Y=0.859＋0.108C （before work, r=0.6200） or Y=1.980＋0.179C （after work, r=0.7930）. Conclusion This method can be used to determine and control the level of urinary ttMA in those who are occupationally exposed to benzene.

Primary NK/T cell lymphoma of the testis:A case report and review of the literature

Objective： To study the clinical and pathological features of primary NK/T cell lymphoma of testis and to investigate the effective diagnosis and treatment of this disease. Methods： The surgical specimens of a patient with primary NK/T cell lymphoma of the testis were observed by light microscopy, immunohistochemistry and examined by the polymerase chain reaction （PCR） for Epstein-Barr virus （EBV） DNA and T-cell receptor （TCR） gene rearrangement, and the literature were reviewed. Results： The patient presented with left-sided painless testicular enlargement and the lymphoma had a propensity to spread to the contralateral testis, spleen, central nervous system, and so on. The neoplastic cells were positive for CD56, CD45R0 and CD3ε, while the expressions of CD20, CD79α, CD5, Bcl-2 and PLAP were negative. In addition, the EBV DNA was detected in the lymphoma by PCR. And the results of gene rearrangement studies for the y chain of the T-cell receptor were negative. The pathological diagnosis was NK/T cell lymphoma of the left testis. Conclusion： Primary NK/T cell lymphoma of the testis is a rare entity and progressed rapidly. The histopathological, immunohistochemical, EBV examination and TCR gene rearrangement studies should be carried out as soon as possible in order to get the defined diagnosis. Currently, the therapeutic efficacy is poor and the new measures should be investigated to improve the survival rate.

Wortmannin induced apoptosis of leukemia cells by reducing PI3K/Akt

Objective： We studied the effects of Wortmannin （WM） on the proliferation and apoptosis of leukemia cells, and explore the possible mechanisms. Methods： The human myeloid leukemia cell line K562 was treated with different concentrations of WM, and then detected the activity of the cell proliferation by MTT assay, comet tail formation of cell DNA damage phenomenon by single cell gel electrophoresis, cell apoptosis byAnnexin V-FITC/PI double staining and the expression levels of total Akt, phoshorylated Akt, NF-KB and protein in K562 cell by Western blotting, RT-PCR test before and after WM. Results： WM inhibited cell proliferation of K562 in a concentration-dependent manner, with IC50 value for 24 h being 25 nmol/L. WM induced apoptosis of K562 cells in a concentration-dependent manner, and could induce the breakage of DNA strand of K562 cell. The rate of DNA tail and the tail length of experimental groups were significantly higher than that of control group. WM may inhibit the expression of phosphorylated Akt and NF-KB protein in a dose-dependent manner in both the protein and gene levels, but no significant effect on total Akt protein. Conclusion： WM inhibited cell proliferation and induced apoptosis in K562 and concentration-dependent manner. The possible mechanism may be involved in the regulation of survival signaling pathway, such as PI3K/Akt/NK-KB.

Effects of shRNA Targeting VEGF on VEGF mRNA Expression in Gastric Cancer Cells

In order to investigate the inhibitory effect of plasmid-mediated short hairpin RNA targeting vascular endothelial growth factor （VEGF） on the expression of VEGF mRNA in human gastric cancer cells, a plasmid vector for transcribing specific short hairpin RNA targeting VEGF （ pU6-VEGF ） was constructed, and then transfected into human gastric cancer cells using Lipofectamine2000. The VEGF mRNA expression level was detected by RT-PCR. RPMI1640 was used for blank control, and pSilencer 1.0-U6 empty plasmid for the negative control. Results showed the clone and sequence analysis revealed that the recombinant plasmid vector of pU6-VEGF was successfully constructed. The VEGF mRNA expression levels in blank control group, experimental group （pU6-VEGF） and negative control group （pSilencerl,0-U6） were 100%, 49% and 94%, respectively, indicating VEGF mRNA expression in the cells transfected with pU-VEGF vector was inhibited significantly as compared with blank control group and negative control group. It was concluded that the short hairpin RNA could significantly inhibit the expression of VEGF mRNA, which provided an experimental basis for treating human cancer with anti-angiogenesis.

Value of Thromboelastography in Judging Abnormal Coagulation Function in Patients with Early Hemorrhagic Shock

Objective: To detect the changes of coagulation function in patients with early hemorrhagic shock by thromboelastography (TEG). Methods: TEG was performed in 50 patients with early hemorrhagic shock and surgical indications. The TEG parameters were compared with 50 healthy people. The coagulation and fibrinolysis in patients with early hemorrhagic shock were observed. Results: In terms of coagulation parameters, the R value decreased, the α angle increased, and the K value and MA value did not change significantly in patients with early hemorrhagic shock. Fibrinolytic aspects: EPL, LY30 observations have no significant changes compared to normal values. Conclusion: The plasma coagulation factor activity is increased in patients with early hemorrhagic shock;the fibrin level is increased;the blood is in a hypercoagulable state;and the fibrinolysis function is not changed. The timely detection of TEG can be used for coagulation function monitoring and blood transfusion therapy in patients with surgical hemorrhagic shock. It provides an important basis for preventing the formation of deep vein thrombosis.

Expression of E2A in Mid-secretory Endometrium of Women Suffering from Recurrent Miscarriage

E2A is involved in promoting forkhead box P3（FOXP3） and retinoid-related orphan receptor gamma t（RORγt） gene transcription, which are pivotal transcription factors of T regulatory cells and Th17 cells, respectively. Little is known about the involvement of E2 A in pregnancy process. This study aimed to investigate the expression of E2 A, cytotoxic T-lymphocyte-associated protein 4（CTLA-4）, and Foxp3 in luteal phase endometrium of women suffering recurrent miscarriage（RM）（n=21） and control group（n=11） by immunohistochemistry, with the Vectra？ automated quantitative pathology imaging system for analysis. The percentage of E2 A＋ cells and CTLA-4＋ cells was significantly higher in the endometrium of women with RM than in the controls. There was positive correlation between E2 A and CTLA-4（r=0.523, P=0.002）, E2 A and FOXP3（r=0.380, P=0.032）, and FOXP3 and CTLA-4（r=0.625, P=0.000） in the mid-secretory phase of endometrium for all subjects. It was concluded that the abnormal expression of endometrial E2 A existed in mid-secretory endometrium of women with RM, and there was a positive correlation between E2 A and FOXP3, and E2 A and CTLA-4, suggesting the possible regulation role of E2 A involved in regulating endometrium receptivity.

Perioperative Nursing Management of an Animal Model of Axial Flow Blood Pump Implantation

This study aimed to explore the characteristics of perioperative nursing of experimental goats using self-made axial-flow blood pump implantation and provided theoretical nursing knowledge and practice-based evidence for the clinical application of domestically manufactured artificial cardiac pumps. Methods: Seven experimental goats were used in this study, three for pre-testing and four for the formal experiments. According to the surgical requirements for axial-flow blood pump implantation into the cardiac apex, we creatively designed and made a series of highly practical animal surgical instruments including a composite disassemblable bed for experimental animal transferring and monitoring, a multifunctional animal surgery bed, and portable medical supporting equipment. We also applied for two national invention patents and one utility model patent. Active measures were taken to ensure careful preparation before surgery, close collaboration during surgery, and effective management of complications after surgery. Results: Two of the four experimental goats died during surgery because of a massive hemorrhage caused by distal anastomotic failure and air embolism-induced cardiac arrest caused by air leakage from the outlet into the heart due to poor connection of the auxiliary pressure tap (used to measure left ventricular pressure). The mean survival time of the remaining three experimental goats was 22.7 hours. Conclusion: This study was the first to systematically and comprehensively investigate the perioperative nursing management of axial-flow blood pump implantation using animal models. These findings could greatly promote further clinical applied nursing research of self-made artificial cardiac pump implantation in experimental goats.

Value of regulatory T cell in predicting the chronic hepatitis C

Objective:To explore the proportion and clinical predictive value of serum regulatory T cells (CD4+CD25+Treg cell) in the treatment process of chronic hepatitis C (CHC) by the interferon. Methods:A total of 94 patients with CHC who were admitted in our hospital for the treatment of peglyated interferon-α and ribavirin were included in the study and were divided into low, moderate, and high loading capacity groups according to HCV-RNA content before treatment. The correlation of different loading capacity with the clinical materials was analyzed. HCV-RNA and the proportion of peripheral blood CD4+CD25+Treg cells after treatment in patients with different response were detected and compared.Results: The comparison of the proportion of peripheral blood CD4+CD25+Treg cells and HCV-RNA among the three groups was statistically significant (P<0.05), and both of them were positively correlated (r=0.845, P=0.001). Among 94 patients, 90 patients had completed 48-week treatment, among which 55 had continuous response, 25 had partial response, and 10 had no response. The proportion of CD4+CD25+Treg cells in the continuous response group and partial response group was significantly reduced when compared with before treatment (P<0.05), while that in the no response group was significantly elevated when compared with before treatment (P<0.05). The comparison of the proportion of CD4+CD25+Treg cells 24 and 48 weeks after treatment among the three groups was statistically significant (P<0.05). CD3+, CD4+, CD8+, and CD4+/CD8+ after treatment in the continuous response and partial response groups were significantly elevated when compared with before treatment (P<0.05). The comparison of CD3+, CD4+, CD8+, and CD4+/CD8+ among the three groups was statistically significant (P<0.05). Conclusions:Interferon in the treatment of CHC can reduce HCV-RNA loading capacity and the proportion of CD4+CD25+Treg cells. HCV-RNA loading capacity in patients with CHC has no correlation with the gender and age, but is positively correlated with the proportion of peripheral blood CD4+CD25+Treg cells. The change of CD4+CD25+Treg cell level can provide a new thought to predict the efficacy in CHC patients.

Differentiation of hMSC in Micromass Culture

1 Introduction Mesenchymal stem cells(MSCs)are multipotential stem cells which can be expanded in culture while still maintaining their undifferentiated state.They have the potential to differentiate into distinct mesenchymal tissue cells,including chondrocytes.Thus,they are an attrac2 tive cell source for cartilage ti ssue engineering.In vitro high density micromass culture has been widely used for chondrogenesis induction.The objective of our study was to analyze viability and differentiation of hMSC in micro2 mass cultures.

Thrombin Activatable Fibrinolysis Inhibitor in Preeclmapsia and Gestational Hypertension throughout the Gestation

To clarify the role of TAFI in hypertensive disorders in pregnancy, 22 subjects, including 10 with pre-eclampsia （PE） and 12 with gestational hypertension were examined for the levels of TAFI and thrombin-antithrombin （TAT） complex. Thirty normal pregnant women served as controls. ELISA was employed for the detection. The results showed that the TAFI antigen levels in normal pregnancy group, gestational hypertension group and PE group were （85.35±24.69）%, （99.65±18.27）%, （110.12±23.36）%; （97.06±21.40）%, （114.08±27.76）%, （125.49±24.70）%; （106.6±19.21）%, （129.2±25.07）%, （139.1±30.12）%, in the 1st, 2nd and 3rd trimester respectively. No significant differences were found between the normal pregnancy group and gestational hypertension group but significant difference existed between normal pregnancy group and PE group in each trimester （P〈0.05）. TAT complexes were significantly higher in patients with PE than that in controls （P〈0.05）, but no correlation was found between TAT and TAFI. It is concluded that TAFI may contributed to the impairment of fibrinolysis in the patients with PE and may serves as a sensitive indicator for PE, but it may not help in the diagnosis of the gestational hypertension.

A Nomogram Model for Predicting Type-2 Myocardial Infarction Induced by Acute Upper Gastrointestinal Bleeding

Objective To examine the independent risk factors of type-2 myocardial infarction(T2MI)elicited by acute upper gastrointestinal bleeding(AUGIB),and to establish a nomogram model for the prediction of AUGIB-induced T2MI.Methods A nomogram model was established on the basis of a retrospective study that involved 533 patients who suffered from AUGIB in the Department of Critical Care Medicine(CCM)or Emergency Intensive Care Unit(EICU)of Renmin Hospital of Wuhan University,Wuhan,China,from January 2017 to December 2020.The predictive accuracy and discriminative power of the nomogram were initially evaluated by internal validation,which involved drawing the receiver operating characteristic(ROC)curve,calculating the area under the curve(AUC),plotting the calibration curve derived from 1000 resampled bootstrap data sets,and computing the root mean square error(RMSE).The predictive ability of the nomogram was further validated through the prospective and multicenter study conducted by the investigators,which enrolled 240 AUGIB patients[including 88 cases from Renmin Hospital of Wuhan University,73 cases from Qilu Hospital of Shandong University(Qingdao),and 79 cases from Northern Jiangsu People’s Hospital)],who were admitted to the Department of CCM or EICU,from February 2021 to July 2021.Results Among the 533 patients in the training cohort,78(14.6%)patients were assigned to the T2MI group and 455(85.4%)patients were assigned to the non-T2MI group.The multivariate analysis revealed that age>65,hemorrhagic shock,cerebral stroke,heart failure,chronic kidney disease,increased blood urea nitrogen,decreased hematocrit,and elevated D-Dimer were independent risk factors for AUGIB-induced T2MI.All these factors were incorporated into the nomogram model.The AUC for the nomogram for predicting T2MI was 0.829(95%CI,0.783-0.875)in the internal validation cohort and 0.848(95%CI,0.794-0.902)in the external validation cohort.The calibration curve for the risk of T2MI exhibited good consistency between the prediction by the nomogram and the actual clinical observation in both the internal validation(RMSE=0.016)and external validation(RMSE=0.020).Conclusion The nomogram was proven to be a useful tool for the risk stratification of T2MI in AUGIB patients,and is helpful for the early identification of AUGIB patients who are prone to T2MI for early intervention,especially in emergency departments and intensive care units.

Green Tea Polyphenols Prevent Early Vascular Aging Induced by High-Fat Diet via Promoting Autophagy in Young Adult Rats

Objective Epidemiology studies indicate that green tea polyphenols(GTP)perform a protective effect on cardiovascular diseases,but the underlying mechanisms are complex.The present study aimed to investigate the effect of GTP on high-fat diets(HFD)induced-early vascular aging.Methods Six-week young adult Wistar rats were fed with standard chow or HFD in the presence and absence of GTP(200 mg/kg body weight)for 18 weeks.In vitro experiment,human umbilical vascular endothelial cells(HUVECs)were treated with palmitic acid(PA)and GTP.Results The results showed that GTP alleviated the disorganized arterial wall and the increased intima-media thickness induced by HFD.In addition,the vascular oxidative injury was suppressed following GTP treatment.Furthermore,GTP elevated the ratio of LC3-II/LC3-I and suppressed expression of p62/SQSTM1,and restored SIRT3 expression in the aorta of HFD rats.Consistently,in cultured HUVECs,GTP inhibited cell senescence indicated by SA-β-gal and promoted endothelial autophagy compared with the PA treatment group.The activity of SIRT3 was specifically inhibited by 3-TYP,and the protective effect of GTP was consequently abolished.Conclusion The findings indicated that GTP protected against early vascular senescence in young HFD rats via ameliorating oxidative injury and promoting autophagy which was partially regulated by the SIRT3 pathway.

Risk Factors for Chemotherapy-Induced Leukopenia in Patients with Lung Cancer

Objective: This analysis was conducted to clarify risk factors for chemotherapy-induced leukopenia (CIL) in lung cancer. Methods: A retrospective study was conducted on data from 358 patients with lung cancer who received chemotherapy. Results: Among 358 cases of lung cancer who received chemotherapy, a total of 240 patients experienced CIL, rate was 67%. The demographic data including gender (P = 0.795), age (P = 0.134), presence of selected chronic comorbidities (P = 0.23) were not significantly different in the two groups. The weight loss rate, PS score, sub-normal pre-WBC level, sub-normal pre-PLT level, and the cycle of chemotherapy were significantly different between the groups (P < 0.05). Multivariate analysis revealed that the weight loss rate ≥5% (OR = 0.503), sub-normal pre-WBC level (OR = 11.807), the cycle of chemotherapy ≥3 (OR = 3.100) were main risk factors for CIL in lung cancer. Conclusion: Before treatment, weight loss rate is 5% or higher, chemotherapy has a cycle of 3 or more and sub-normal WBC level is independent risk factor of lung cancer after chemotherapy-induced leucopenia.