Factors Influencing and Adverse Reactions of Voriconazole Clearance in Patients with Hematological Diseases / 中国实验血液学杂志

OBJECTIVE@#To monitor the changes of voriconazole minimum concentration(Cmin) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole.@*METHODS@#136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole Cmin were analyzed, and the changes of voriconazole Cmin after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole.@*RESULTS@#Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole Cmin and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole Cmin was negatively correlated with albumin level (r=-2.673). Voriconazole Cmin in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole Cmin showed that compared with voriconazole Cmin 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole Cmin> 5.0 mg/L group was increased (χ2=4.318, P=0.038).@*CONCLUSION@#The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole Cmin, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole Cmin of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.

Delicaflavone inhibits the invasion and migration of gefitinib-resistant lung cancer PC-9/GR cells by regulating epithelial-mesenchymal transition via PI3K/Akt/mTOR pathway / 中国临床药理学与治疗学

AIM: To study the effect and mechanism of Delicaflavone on migration and invasion of gefitinib-resistant lung cancer cell line PC-9/GR. METHODS: MTT assay was used to detect cell viability. Transwell and scratch assays were used to detect cell invasion and migration abilities. Western blotting was used to detect the expressions of MMP-9, MMP-2, E-cadherin, N-cadherin, Vimentin and PI3K/Akt/mTOR pathway-related proteins in PC-9/GR cells. RESULTS: Compared with control group, 20 mg/L Delicaflavone could significantly inhibit the viability of PC-9/GR cells for 24 h (P<0.05), while Delicaflavone below 10 mg/L had no significant effect on cell proliferation. The number of invasive cells and migrated cells were decreased significantly by Delicaflavone in a concentration-dependent way (P<0.05 and P<0.01). Delicaflavone could concentration-dependently reduce the expression of MMP-9, MMP-2, N-cadherin, vimentin (P<0.01), meanwhile up-regulate the expression of E-cadherin (P<0.01). In addition, Delicaflavone also decreased the expression of p-PI3K, p-Akt and p-mTOR in a concentration-dependent manner (P<0.01). CONCLUSION: Delicaflavone can inhibit the migration and invasion of PC-9/GR cells by regulating epithelial-mesenchymal transition via PI3K/Akt/mTOR pathway.

Inhibition of Sonic Hedgehog signaling inhibits fibrous scar formation and adversely affects functional outcome after ischemic brain injury in rats / 南方医科大学学报

OBJECTIVE@#To investigate the effects of inhibiting Sonic Hedgehog (Shh) signaling on fibrous scar formation and functional outcome after ischemic brain injury.@*METHODS@#Adult SD rats were randomized into sham-operated group, middle cerebral artery occlusion (MCAO) and reperfusion (I/R) group, I/R with intraventricular empty adenoviral vector (rAd-NC) injection group, and I/R with adenovirus-mediated Shh knockdown (rAd-ShShh) group. After the treatments, the neurological deficits of the rats were assessed, and the protein and mRNA expressions of fibronectin (Fn), α-SMA, and Shh in the ischemic hemisphere were detected with immunofluorescence assay and qPCR; TUNEL staining was used for detecting neural cell apoptosis. In the cell experiment, primary meningeal fibroblasts isolated from neonatal SD rats were pretreated for 24 h with TGF-β1 or TGF-β1 plus cyclopamine (CYC) before oxygen-glucose deprivation for 150 min followed by reoxygenation for 72 h (OGD/R). CCK-8 assay and scratch test were performed to examine the changes in cell proliferation and migration, and immunofluorescence assay, qPCR and Western blotting were used for detecting cell transformation and the expressions of Shh, α-SMA, and Fn.@*RESULTS@#Cerebral I/R injury significantly increased the protein and mRNA expressions of Shh, α-SMA, and Fn in the ischemic hemisphere of the rats, but their expression levels were significantly lowered by intraventricular injection of rAd-Shshh (P < 0.05), which obviously increased cell apoptosis in the ischemic hemisphere (P < 0.05) and improved modified mNSS and modified Bederson scores of the rats (P < 0.05). In the cell experiment, pretreatment with TGF-β1 and TGF-β1+CYC both increased the viability of the primary meningeal fibroblasts after OGD/R. TGF-β1 significantly enhanced the migration ability and induced obvious transformation of the exposed cells (P < 0.05), but these effects were significantly attenuated by co-treatment with CYC (P < 0.05). The expressions of Shh, α-SMA and Fn in the TGF-β1 group were all significantly higher in TGF-β1-treated cells (P < 0.05) and were obviously lowered by co-treatment with CYC (P < 0.05).@*CONCLUSION@#Inhibition of Shh signaling may inhibit fibrous scar formation and functional recovery in rats after ischemic brain injury.

Transforming growth factor-β1 induces transformation of rat meningeal fibroblasts into myofibroblasts by upregulating Shh signaling / 南方医科大学学报

OBJECTIVE@#To investigate the effect of TGF-β1 on Shh signaling pathway during the transformation of meningeal fibroblasts into myofibroblasts.@*METHODS@#Primary meningeal fibroblasts were isolated from neonatal (24 h) SD rats and purified using type Ⅳ collagenase. The isolated cells were treated with 10 ng/mL TGF-β1 alone or in combination with 20 μmol/L SB-431542 (a TGF-β1 receptor inhibitor) for 72 h, and the changes in proliferation and migration abilities of the fibroblasts were assessed with CCK-8 assay and cell scratch test. The expression of fibronectin (Fn) was detected with immunofluorescence assay, and Western blotting was performed to examine the expressions of Fn, α-SMA and Shh protein in the cells; the expression of Shh mRNA was detected with real-time fluorescence quantitative PCR.@*RESULTS@#TGF-β1 treatment obviously enhanced the proliferation and migration of primary meningeal fibroblasts (P < 0.05), and promoted the transformation of meningeal fibroblasts into myofibroblasts and the secretion of Fn (P < 0.05). TGF-β1 treatment also upregulated the expression of Shh at both protein and mRNA levels (P < 0.05). Treatment with SB-431542 partially blocked the effect of TGF-β1 on the transformation of meningeal fibroblasts (P < 0.05).@*CONCLUSION@#TGF-β1 can induce the transformation of meningeal fibroblasts into myofibroblasts by up-regulating Shh expression in Sonic Hedgehog signaling pathway.

Autophagy and intrauterine growth retardation / 中国药理学通报

Autophagy is involved in the development of multiple organs, and abnormal autophagy can affect the growth and development of the body. Intrauterine growth retardation (IUGR) is one of the most common developmental toxicities, which can lead to increased perinatal morbidity and mortality of offspring, and the damage continues to cause adult susceptibility to a variety of chronic diseases after birth. This review mainly reviewed the pathogenesis of autophagy and its relationship with IUGR, so as to provide a theoretical basis for the study of autophagy in IUGR-related diseases.

Advances on nonviral vectors of CRISPR/Cas9 system for genome editing / 药学学报

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein system exerts genome editing effect through cleaving DNA double strands using RNA-guided endonuclease. Double-strand breaks were repaired via homology directed repair (HDR) or nonhomologous end joining (NHEJ), accompanied by insertions, deletions or replacements into the genome. As a powerful tool, CRISPR/Cas system has provided tremendous convenience for basic researches and may pave the path to treat genetic diseases and cancers. Genome editing could be achieved only when both CRISPR RNA and Cas protein are delivered into nucleus of target cell. Compared with physical and viral delivery, nonviral delivery of CRISPR/Cas system possesses unique advantages in terms of safety, loading capacity and preparation. Hence, many researchers have devoted themselves to the development of nonviral vectors with high delivery efficiency which is important for the application and translation of the promising technology. Advances on cationic liposomes, lipid like nanoparticles, cationic polymers, AuNPs, vesicles, polypeptides, proteins and so on have been made. We will give a brief introduction to the mechanism of CRISPR/Cas9, problems faced by nonviral delivery of CRISPR/Cas9 system in forms of plasmid, mRNA and protein; examples of non-viral vectors, hoping to give some hints on design of safe and efficient nonviral vectors for genome editing.

Spatial point pattern analysis of hemorrhagic fever with renal syndrome in Jingzhou, Hubei Province, 2017 / 中华疾病控制杂志

Objective To analyze the spatial point pattern distribution characteristics of hemorrhagic fever with renal syndrome (HFRS) in Jingzhou city, Hubei province during the two seasons spring- summer and autumn-winter of 2017, to discuss its high incidence area and reason, and to provide basis for the resource allocation of public health. Methods The analytical data was collected from Infectious Disease Reporting Information System in China, and the spring-summer season was from March to August of 2017, while the autumn-winter was from the September of 2017 to the February of 2018. The Ripley's K-function and kernel density estimation were applied to analyze the spatial point pattern distribution and compare the distribution characteristics of spatial point pattern between the two seasons. Results In 2017, 133 cases of HFRS were reported in Jingzhou city, including the spring- summer and autumn-winter two pick incidences. The strongest aggregation distance was 17.77km in spring-summer season, and 14.40 km in autumn-winter season. The spatial gathering center was located in the north of Jianli County in spring-summer, and it moved to the south of Jiangling County and Shashi District in autumn-winter. Conclusions The key areas for the prevention and control of HFRS in Jingzhou City are Jiangling County, the southern part of Shashi District and the northern part of jianli county. The key groups are the residents of the urban-rural junction in the southern part of Shashi City, residents along the route of large-scale projects, and farmers engaged in agricultural planting or crayfish breeding in the gathering areas.

Effects of Shuwei Decoction on the expressions of Beclin-1, mTOR, Cx43 Protein and mRNA in gastrointestinal smooth muscle of rats with functional dyspepsia due to liver depression and spleen deficiency / 中成药

AIM To investigate the therapeutic action and mechanism of Shuwei Decoction (Bupleuri Radix,Cyperi Rhizoma,Atractylodis macrocephalae Rhizoma,etc.) on functional dyspepsia (FD) from the perspectives of autophagy and intercellular gap junction pathway through its impact on the expressions of Beclin-1,mTOR,Cx43 protein and mRNA in gastric antrum pyloric smooth muscle cells of FD model rats.METHODS Sixty Wistar rats were randomly divided into control (blank) group,model group,mosapride group (1.37 mg/kg),low,medium and high dose Shuwei Decoction groups (7.67 g/kg,15.34 g/kg,30.68 g/kg,respectively).FD model rats were prepared according to compound etiological modeling method for 21 days.On the first day after modeling,the rats in each group were given the corresponding medicine for intragastric administration once a day for 14 days.Two hours after the last administration,we procured gastric antrum and pyloric tissues from the sacrificed rats.The expressions of Beclin-1,mTOR and Cx43 protein were detected by Western blot,and so were the expressions of Beclin-1,mTOR and Cx43 mRNA by quantitative real-time PCR (RT-qPCR).RESULTS We observed decreased expression of Beclin-1 protein in low,medium and high dose Shuwei Decoction groups (P ＜ 0.01),and an increased expression of Cx43 protein in high dose Shuwei Decoction group (P ＜ 0.05).In medium and high dose Shuwei Decoction groups,decreased expression of Beclin-1 mRNA (P ＜ 0.01),and increased expression of mTOR and Cx43 mRNA (P ＜ 0.01) were detected as well.CONCLUSION Shuwei Decoction can improve FD by suppressing cell autophagy and enhancing the function of gap junction through up-regulating the expression of mTOR mRNA and Cx43 protein and mRNA,and down-regulating the expression of Beclin-1 protein and mRNA.

The Effect of PCSA with Parecoxib Sodium and Sufentanil on the Postoperative Delirium in Patients after the Spinal Surgery / 昆明医科大学学报

Objective To investigate the effect of patient controlled subcutaneous analgesia (PCSA) of Sufentamil and Parecoxib sodium on the postoperative delirium in patients after the spinal surgery. Methods 240 patients with ASA Ⅱ- Ⅲ age 18-64 yrs after the spinal surgery were divided into two groups: group NO-PCSA (analgesic management: patients were accepted pethidine 25-50 mg intramuscular injection n = 120 );group PCSA (analgesic management: patient controlled subcutaneous analgesia was started since skin suture with the following composition:Sufentanil 0.9 ug/(kg.d)+Parecoxib sodium 120 mg+Tropisetron 10 mg+normal saline 150 mL. The PCSA setting was as follows:background infusion at 2 mL/h, a bolus dose of 0.5 mL, lockout interval 15 min. If the VAS was greater than 5, patient was accepted pethidine 25-50 mg intramuscular injection n=120) . The effect of analgesia was assessed by visual analogue scale (VAS) . The delirium was assessed by the confusion assessment, VAS and delirium were recorded with in 2, 24, 48, 72 hours postoperatively. Results During the analgesia period, the VAS and the incidence of postoperative delirium were significantly lower in group PCSA than those in group NO-PCSA ( <0.05) . Conclusion PCSA of Sufentamil and Parecoxib sodium have a good postoperative analgesic effect in patients after the spinal surgery. It is an effective measure and the incidence of postoperative delirium can be decreased by reliefing postoperative pain.

Accumulation of biomass and four triterpenoids in two-stage cultured Poria cocos mycelia and diuretic activity in rats / 中国天然药物

Poria cocos (Schw.) Wolf, an important medicinal and food fungus, is well known in East Asia. Due to growing market demand, long cultivation period, and consumption of pine trunk during cultivation, developing alternative methods for producing P. cocos and/or its active components is of interest. In the present study, the effects of different culture methods on biomass and accumulation of four triterpenoids were investigated. The ethanol extract of fermented mycelium (EFM) was orally administered to rats. Urine output and concentrations of electrolytes (Na, K, and Cl) were measured. Our results showed that mycelia grew better under continuous shaking culture condition (7.5 g DW·L), and higher triterpenoid levels were accumulated in two-stage culture (112 mg·L, 2.03%). The optimal starting time of static culture for triterpenoid yield was 4 d after shaking culture. Single administration of middle and high dose of EFM significantly increased urine output, Na and Cl excretion, and Na/K ratio. These results suggested that ethanol extract of cultured mycelia showed significant diuretic activity in rats and two-stage culture of P. cocos could be an alternative way to produce mycelia and triterpenoids.

Clinical features and VPS33B mutations in a family affected by arthrogryposis, renal dysfunction, and cholestasis syndrome / 中国当代儿科杂志

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations in the VPS33B or VIPAS39 gene. The aim of this study was to investigate the clinical features and VPS33B gene mutations of an infant with ARC syndrome. A 47-day-old female infant was referred to the hospital with the complaint of jaundiced skin and sclera for 45 days and abnormal liver function for 39 days. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined diagnosis. Physical examination showed jaundice of the skin and sclera. Systemic skin was dry with desquamation in the limbs and trunk. There were no positive signs on cardiopulmonary examination. The liver was palpable 2.0 cm under the right subcostal margin. The hips and knees were flexed, and the extension was limited, with low muscular tone in the four limbs. Biochemical analysis demonstrated raised serum total bile acids, bilirubin (predominantly conjugated bilirubin) and transaminases, but the γ-glutamyl transpeptidase level was normal. Routine urine test revealed increased glucose as well as red and white blood cells. On genetic analysis, the infant was proved to be homologous for a VPS33B mutation c.1594C>T(p.R532X). She was definitely diagnosed to have ARC syndrome. Symptomatic and supportive therapy was given, but no improvement was observed, and the infant finally died at 3 months and 29 days of life.

Study on influencing factors of local recurrence after breast conserving surgery in young patients with breast cancer / 重庆医学

Objective To investigated the influence factors of local recurrence after breast conserving therapy (BCT) in young patients with breast cancer.Methods A total of 360 cases of BCT in this hospital from January 2005 to January 2010 were collected and retrospectively analyzed.Clinical and pathological data included the tumor size,lymph node status,tumor TNM stage,pathological type,margin status,human epidermal growth factor receptor 2 (Her-2),estrogen receptor (ER)/progesterone receptor (PR) and Ki-67.The independent risk factors were analyzed by adopting the univariate analysis and Logistic regression analysis.Results The total recurrence rate of young patients with BCT was 10.56％.The univariate analysis showed that the tumor size,TNM stage,pathological type and ER/PR ratio had no influence on local recurrence after BCT in young patients (P＞0.05);lymph node metastasis,cutting edge status,Her-2 and Ki-67 could influence the local recurrence rate after BCT in young patients (P＜0.05).The Logistic regression analysis showed that the lymph node status,Her-2 and margin status were the independent risk factors for local recurrence after BCT in young patients (P＜0.05).Conclusion Lymph node metastases,Her-2 positive and cutting edge status are local recurrence risk factor after BCT for young patients with breast cancer

Correlative analysis of three sperm indexes and IVT-ET outcome after semen treatment / 重庆医学

Objective To investigate the correlation between three sperm indexes and the outcome of in vitro fertilization and embryo transfer(IVT-ET) before and after semen treatment.Methods The semen derived from 298 male patients treated with IVT-ET from the Affiliated Hospital of Southwest Medical University was retrospectively analyzed.Routine analysis of semen before treatment was performed according to the WHO standard.Vitrolife density gradient centrifugation combined with upstream method was used to analyze sperm parameters after sperm analysis,and the observation and statistics were performed after fertilization and sequential culture to day 3.Results The total viability of spermatozoa before and after semen treatment,the percentage of normal spermatozoa,sperm density,and other differences were statistically significant (P＜0.05);The normal sperm morphology rate was positively correlated with fertilization rate(r=0.487,P＜0.01) and cleavage rate(r=0.250,P＜0.05);The sperm vitality of post-processed semen was positively related to the fertilization rate (r =0.249,P＜0.05,);and significantly cleavage rate (r =0.272,P＜0.05);After treatment,sperm density was positively correlated with 2 PN(r=0.609,P＜0.01) and multiple PN fertilization rates(r=0.243,P＜0.05).Conclusion Our experimental results indicate that the parameters of post-processed sperm treated at the day when the oocytes were collected may be more helpful in predicting the fertilization rate and cleavage rate of IVF-ET.Therefore,the IVF-ET treatment protocols should be chose based on the normal sperm morphology rate and sperm vitality after semen treatment.

Effects of Chinese herbal compound "Jisuikang" on phagocytosis of microglia and regeneration of injured neurons in co-culture system / 中国免疫学杂志

Objective:To observe the effects of Chinese herbal compound'Jisuikang'on the phagocytosis of microglia and the regeneration of injured neurons in co-culture system.Methods: Prepared drug serum of 'Jisuikang′ and isolated and identified the primary neuron and microglia.The neuron cells were induced apoptosis by glutamic acid and the microglia cells were predisposed by drug serum of'Jisuikang'.Then,the co-culture system of injured neurons and microglia cells was established.24 h and 96 h after co-culture,engulfment of neuron debris by microglia cells and regeneration of injured neurons were observed by immunofluorescence double labeling method.Results: 24 h after co-culture,middle and high dose of'Jisuikang' showed greater phagocytic percentage and phagocytic index than that of control.In comparison of LPS,high dose of'Jisuikang' showed no significant difference.96 h after co-culture,first grade of neuritis of middle and high dose of'Jisuikang' were more than that of control,and there were no significant difference in comparison of LPS.Neuritis' mean length per cell of middle and high dose of'Jisuikang' were larger than that of con-trol.Neuritis' mean length per cell of high dose of'Jisuikang' showed significant difference in comparison of LPS.Conclusion:Traditional Chinese medicine compound'Jisuikang'may enhance engulfment of neuron debris by microglia to improve local microenvi-ronment,which promote the repair and regeneration of injured neurons.

Reconstruction for knee dislocation with multiple ligaments injury at stage I / 中国骨伤

<p><b>OBJECTIVE</b>To investigate clinical outcomes of tendon allograft reconstruction with arthroscopy minimally invasive technique at stage I for the treatment of knee dislocation with multiple ligaments injury.</p><p><b>METHODS</b>Forty-eight patients with knee dislocation were reconstructed anterior and posterior ligament under arthroscopy at stage I from January 2008 to January 2012, and repaired ligaments injury of knee joint by minimally invasive technique. There were 38 males and 10 females aged from 20 to 59 years old with an average of 35.6 years old; 22 cases on the left side and 26 cases on the right side; the time from injury to operation ranged from 2 d to 2 weeks. Two cases combined with anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL) and posterolateral complex injuries, 36 cases combined with ACL, PCL, and MCL injuries, 10 cases combined with ACL, PCL and PLC injuries; 4 cases combined with peroneal nerve injury. Lysholm scoring were used to compared the cases before operation and final following-up to evaluate knee function.</p><p><b>RESULTS</b>All patients were followed up from 12 to 30 months with an average of (18.2 ± 6.3) months. Activity and stability of joint were obviously improved. Lysholm score were improved from 40.3 ± 4.1 before operation to 87.0 ± 6.4 at final following-up.</p><p><b>CONCLUSION</b>Reconstruction with arthroscopy minimally invasive technique at stage I for the treatment of knee dislocation with multiple ligaments injury could recover stability of joint better,reserve joint function. Preoperative training and postoperative individualized rehabilitation treatment is the key point of recover knee joint function.</p>

Effect of primary cilia-mediated shh signaling on neuronal-like cell differentiation of rat bone marrow stromal cells / 第二军医大学学报

To study the effect of primary cilia-mediated sonic hedgehog (Shh) signaling on differentiation of rat bone marrow stromal cells (MSCs) into neuron-like cells. Methods Rat MSCs were isolated and cultured. The study was divided into normal resveratrol-cultured group, resveratrol-induced group, SAG (Smoothened [Smo] agonist) group, and cyclopamine (Smo inhibitor) group. Cell morphology was observed under inverted microscope; the expressions of Ac-Tu, Ptc, Smo, and Glil were examined by immunofluorescence method. Western blotting analysis was used to detect the protein expressions of Smo and Gli, and RT-PCR was applied to detect mRNA expressions of Smo and Glil. Results No expression of primary cilia was found in the normally cultured MSCs. After pre-induction or 24 h starvation, MSCs expressed primary cilia, Ptc, Smo and Glil proteins, with Ptc protein in the primary cilia and Smo, Glil in the cytoplasm. In normal cultivation, resveratrol did not promote the translocation of Smo or induce differentiation of MSCs into neuronal-like cells. When MSCs expressed primary cilia, resveratrol and SAG led to translocation of Smo from the cytoplasm into primary cilia, accompanied by MSCs differentiation into neuronal-like cells and significantly increased expression of Smo and Glil mRNA and protein (P< 0. 05). When cyclopamine was added, Smo remained expressed in the cytoplasm, the expression of Smo and Glil mRNA and protein was significantly decreased (P < 0. 05), and MSCs differentiation into neuronal-like cells was inhibited. Conclusion MSCs express primary cilia and have Shh signaling. Primary cilia-mediated Shh signaling participates in MSCs differentiation into neuronal-like cells.

Effect of puerarin combined with felodipine on mRNA and protein expression of apelin and APJ in renovascular hypertensive rat / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the effect of puerarin combined with felodipine on the mRNA and protein expression of apelin and APJ in renal tissue of renovascular hypertensive rat.</p><p><b>METHOD</b>Sixty-two Sprague-Dawley rats were used, of which 8 rats were randomly chosen as sham-operation group. The remaining rats were made for the rat model with renovascular hypertension. The renovascular hypertensive rats were randomly divided into 5 groups as follows: 4 groups which were treated with felodipine (0.8 mg x kg(-1) x d(-1)), puerarin (50 mg x kg(-1) x d(-1)), puerarin combined with felodipine (puerarin 25 mg x kg(-1) x d(-1) + felodipine 0.4 mg x kg(-1) x d(-1)) or captopril combined with felodipine (captopril 15 mg x kg(-1) x d(-1) x felodipine 0.4 mg x kg(-1) x d(-1)), and 1 group which was treated with distilled water. Drugs or distilled water were administered for 8 weeks. The expression of apelin and APJ mRNA and protein in ischemic and non-ischemic kidneys was assessed by RT-PCR or Western blot.</p><p><b>RESULT</b>Compared with sham-operation group, the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys in model group was increased significantly (P < 0.01); the expression of APJ mRNA and protein in ischemic kidneys had no significance, while that in non-ischemic kidneys was decreased (P < 0. 01). Compared with model group, the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys was decreased significantly in all drug-treated groups (P < 0.01); while that of APJ mRNA and protein in non-ischemic kidneys was upregulated (P < 0.01). Compared with felodipine group, the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys was decreased (P < 0.01 or P < 0.05) in the group treated with both puerarin and felodipine; and the expression of APJ mRNA and protein in ischemic kidneys did not reach significant level, however, that was upregulated in non-ischemic kidneys (P < 0.01 or P < 0.05).</p><p><b>CONCLUSION</b>Puerarin downregulates the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys, and upregulates that of APJ mRNA and protein in non-ischemic kidneys. Combination of puerarin and felodipine enhances the above-mentioned effects and shows no significant difference versus the combination of felodipine and captopril. The results suggest that puerarin regulates blood pressure and protects target organ through apelin/APJ pathway and that puerarin has synergetic effects with CCB.</p>

Ultrasound-triggered microbubble destruction in combination with cationic lipid microbubbles enhances gene delivery / 华中科技大学学报（医学）（英德文版）

This study aimed to examine the preparation of cationic lipid microbubble (CLM), and evaluate its physical and chemical properties and toxicity, measure the gene transfection efficiency by ultrasound triggered microbobble destruction (UTMD) in combination with CLM. The CLM was prepared by the method of the thin film hydration, and its morphology was observed under the electron microscopy at 1st, 3rd, 7th, 10th, and 14th day after preparation, respectively. The size, Zeta potential and stability of CLM were tested. The acute toxicity of CLM was assessed. The green fluorescent protein gene (EGFP) transfection efficiency was evaluated. The experiment grouping was as follows: naked plasmid group (P group), ultrasonic irradiation plus naked plasmid group (P-US group), naked plasmid plus CLM group (P-CLM group), naked plasmid plus ultrasound and CLM group (UTMD group). The expression of EGFP was detected by fluorescent microscopy and flow cytometry. The results showed that CLMs were spherical in shape, with the similar size and good distribution degree under the light and electron microscopies. The size of CLMs was varied from 250.4±88.3 to 399.0±99.8 nm and the Zeta potential of CLMs from 18.80±4.97 to 20.1±3.1 mV. The EGFP expression was the strongest in the UTMD group, followed by the P-CLM group, P-US group and P group. Flow cytometry results were consistent with those of fluorescent microscopy. The transfection efficiency was substantially increased in the P-US group, P-CLM group and UTMD group as compared with that in the P group, almost 7 times, 10 times and 30 times higher than that in the P group respectively. It is suggested that CLMs prepared by the method of thin film hydration are uniform in diameter, and proved non-toxic. UTMD combined with CLM can significantly increase the transfection efficiency of EGFP to targeted cells.

Assessment of left atrial function in diabetes mellitus by left atrial volume tracking method / 华中科技大学学报（医学）（英德文版）

The value of the left atrial volume tracking (LAVT) method in the evaluation of left atrial (LA) function in patients with diabetes mellitus (DM) was examined in this study. Fifty-eight DM patients as DM group and 40 healthy people as normal control group were enrolled in this study. EUB-6500 echocardiographic imaging system with LAVT was applied to display and analyze the LA volume curve imaging on LV apical two and four chamber views. The maximal LA volume at end-systole (LAV(max)), LA volume at the onset of ECG-P wave (LAV(p)), the minimal LA volume at end-diastole (LAV(min)) from the LA volume curve were acquired and recorded. All values above were standardized by body surface area (BSA). Then the passive, active and total LA volume (LAVIpass, LAVIact, LAVItotal) and empting rate (%LAVIpass, %LAVIact, %LAVItotal), effective passive and active empting rate (%eLAVIpass, %eLAVIact), and the proportionality of passive empting volume and active empting volume were calculated. The LAVIp, LAVIact, LAVItotal, %LAVIact, %LAVItotal and %eLAVIact were significantly higher in the DM group than those in the control group, whereas the LAVIpass, %LAVIpass, %eLAVIpass and LAVIpass/act were lower (all P<0.05). For the LA volume change in DM, the active empting volume was enhanced at end-diastole. It was concluded that LAVT is a potentially useful tool to evaluate the function of LA.

Assessment of left atrial function in diabetes mellitus by left atrial volume tracking method / 华中科技大学学报（医学）（英德文版）

The value of the left atrial volume tracking (LAVT) method in the evaluation of left atrial (LA) function in patients with diabetes mellitus (DM) was examined in this study. Fifty-eight DM patients as DM group and 40 healthy people as normal control group were enrolled in this study. EUB-6500 echocardiographic imaging system with LAVT was applied to display and analyze the LA volume curve imaging on LV apical two and four chamber views. The maximal LA volume at end-systole (LAV(max)), LA volume at the onset of ECG-P wave (LAV(p)), the minimal LA volume at end-diastole (LAV(min)) from the LA volume curve were acquired and recorded. All values above were standardized by body surface area (BSA). Then the passive, active and total LA volume (LAVIpass, LAVIact, LAVItotal) and empting rate (%LAVIpass, %LAVIact, %LAVItotal), effective passive and active empting rate (%eLAVIpass, %eLAVIact), and the proportionality of passive empting volume and active empting volume were calculated. The LAVIp, LAVIact, LAVItotal, %LAVIact, %LAVItotal and %eLAVIact were significantly higher in the DM group than those in the control group, whereas the LAVIpass, %LAVIpass, %eLAVIpass and LAVIpass/act were lower (all P<0.05). For the LA volume change in DM, the active empting volume was enhanced at end-diastole. It was concluded that LAVT is a potentially useful tool to evaluate the function of LA.