BACKGROUND: The decrease of activity level of choline acetyltransferase (ChAT) and reduction of membrane protein of synaptic vesicles are the main biochemical indexes in Alzheimer disease. Traditional Chinese bushen yizhi formula is of the effects of strengthening the kidney, replenishing qi, generating marrow and nourishing the brain, its medicine-containing serum can effectively protect these changes resulting from amyloid protein.OBJECTIVE: To investigate whether the medicine-containing serum of bushen yizhi formula can improve the pathological injury of neurons induced by amyloid protein metabolites in Alzheimer disease, thus to estimate the therapeutic effect of bushen yizhi formula on Alzheimer disease.DESIGN:A randomized and controlled trial. SETTING:Institute of Neuroscience, Second Affiliated Hospital, Guangxi College of Traditional Chinese Medicine, Nanning 530011, Guangxi Zhuang Nationality Autonomous Region, China; Encephalopathic Institute of Guangzhou University of Traditional Chinese Medicine.MATERIALS:The experiment was conducted from September 2003 to March 2004 at the Research and Development Center of New Drugs of Guangxi College of TCM. Totally 60 healthy Wistar rats of clean grade,three months, were at random divided as blank control and bushen yizhi groups, with 30 in each group. The bushen yizhi formula consisted of Fructus Lycii, Fructus Cnidii, Radix Gingeng, Radix Polygoni Multiflori,Cortex Moutan Radicis, Borneolum, etc. The medicine was prepared before use as 0.176 g/Ml liquid(including 1.13 g/Ml rude drugs).METHODS:① Each of the rats in bushen yizhi group was by garage given 1.0-1.5 Ml prepared liquid per day for consecutive 30 days. Within 4hours after the last administration the serum was isolated at 5 000 r/min for 5 minutes, filtered aseptically, the compliment was inactivated at 56 ℃,then the medicine-containing serum was obtained. The rats in blank control group were given saline of the same volume, and the serum was prepared with the same method. ② For NG108-15 cells, the concentration of amyloid protein 25-35 segments in the culture liquid was 5 μ mol/L, or 1-42 segments, 200 nmol/L, was suitable. ③ NG108-15 cells was first in cubated for a day in CO2 incubator with Dulbecco-improved Eagle medium of 0.1 molarity at 37 ℃, then 5 μmol/L amyloid protein 25-35 segment or 200 nmol/L segment 1-42 was added to continuously incubate for a day, after that the cell models of Alzheimer disease was ready. Then 50 g/L medicine-containing serum or Dulbecco-improved Eagle medium of blank control group serum was taken to replace the original culture liquid, and the amyloid protein segments of the above-mentioned concentration was still added for maintaining the cell models of Alzheimer disease, after 5 days'differentiation incubation, the indexes were detected with those in non-amyloid protein as control. ④ Western blotting, radioimmunoassay and electrophysiological examination were used to investigate the ChAT activity,synapsin protein level and rate of functional synapse formation of NG108-15cells in Alzheimer disease after treatment with the medicine-containing serum of bushen yizhi formula.MAIN OUTCOME MEASURES :The effects of the medicine-containing serum of bushen yizhi formula on ChAT activity, synapsin protein level,rate of functional synapse formation of NG108-15 cells and frequency of miniature plate potential in NG108-15 cells.RESULTS:Totally 60 rats involved all entered the final result analysis.① The effect of the medicine-containing serum of bushen yizhi formula on ChAT activity: In the conditions when there was no amyloid protein or the final concentration of amyloid protein 1- 42 was 200 nmol/L, the ChAT activity in bushen yizhi group was obviously higher than that in blank control group [(1651.2±134.5), (1336.1±268.2), ( 586.1±223.4),(1290.7±381.5)μmol/(g·h); P ＜ 0.05] . ② The effect of the medicinecontaining serum of bushen yizhi formula on synapsin protein level: The absorbance values of synapsin Ⅰa and Ⅰb, in the conditions when there was no amyloid protein, amyloid protein 25-35 and 1-42, were respectively 5.02, 1.36 and 2.46 in bushen yizhi group; and 3.18, 0.57 and 0.71 in blank control group. The values in bushen yizhi group were respectively 1.6,2.4 and 3.5times those in blank control group. ③ The effect of the medicine-containing serum of bushen yizhi formula on functional synapse formation of NG108-15 cells: In the conditions when there was no amyloid protein or amyloid protein 1-42, the levels of functional synapse formation in bushen yizhi group wereall higher than those in blank control group [(90.6±6.0)%, (63.2±17.0)%, (58.0±13.1)%, (34.2±13.0)% ;P＜0.05].④ The effect of the medicine-containing serum of bushen yizhi formula on frequency of miniature plate potential in NG108-15 cells: In the conditions when there was no amyloid protein or amyloid protein 1-42, the frequencies of miniature plate potential in bushen yizhi group were all higher than those in blank control group [(9.28±4.1), (5.48 ±5.14), (5.55±5.85),(3.05±4.46)/min; P ＜ 0.01, P＜ 0.05].CONCLUSION:In the conditions when there existed no amyloid protein or amyloid protein, the medicine-containing serum of bushen yizhi formula can raise ChAT activity, not only correct the decrease of cellular synapsin caused by amyloid protein, but also raise the expression of synapsin protein, the rate of functional synapse formation and neurotransmitter release under the condition of no amyloid protein. It was shown that the prescription can antagonize the pathological development of Alzheimer disease, and play the therapeutic effect through enhancing the release power of neurotransmitter.

ObjectiveTo investigate the role of the benzodiazepine receptor in the amnesic effect of propofol,etomicdate and ketamine in mice.MethodsTwo hundred and eighty-eight Kunming mice of both sexes weighing 18-23 g were randomly divided into 9 groups( n =32 each):gruup normal saline + normal saline (group NN); group normal saline+ fat emulsion (group NF); group flumazenil + normal saline (group FN); group normal saline + propofol (group NP) ; group flumazenil + propofol (group FP) ;group nomal saline + etomidate (group NE) ; group flumazenil + etomidate (group FE); group normal saline + ketamine (group NK) and group flumazenil + ketamine (group NK).Normal saline 10 ml/kg was given IP at 10 min before the tests,and normal saline 10 ml/kg,fat emulsion 10 ml/kg,propofol 25 mg/kg,etomidate 3 mg/kg and ketamine 20 mg/kg at 5 min before the tests in groups NN,NF,NP,NE and NK respectively.Flumazenil 1 mg/kg was given IP at 10 min before the tests,and normal saline 10 ml/kg,fat emulsion 10 ml/kg,propofol 25 mg/kg,etomidate 3 mg/kg and ketamine 20 mg/kg at 5 min before the tests in groups NN,NF,NP,NE and NK respectively.Darkness-avoiding test,platform-mounting test and Morris water maze test were performed to assess the cognition function.The latency of response and number of error were recorded in each test.ResultsPropofol,etomidate and ketamine significanfly shortened the duration of latency of response in platform-mounting test as compared with group NN.Etomidate also significantly increased the number of error in platform-mounting test as compared with group NN,while ketamine prolonged the duration of latency of response in Morris water maze test as compared with group NN.Flumazenil significantly counteracted the above action of the 3 intravenous anesthetics.ConclusionBenzodiazepine receptor may play an important role in the amnesic effect induced by propofol,etomidate and ketamine.

Objective To investigate the effects of Kruppel-like factor 6 (KLF6) on the apoptotic and migration ability of HepG2 cell, and the developmental role of KLF6 on zebrafish liver.Methods Constructed plasmid with shRNA-KLF6 was transfected in HepG2 and L-02.The impacts of loss of KLF6 on HepG2 was investigated by Western bolt, apoptosis analyses, cell cycle detection and scratch experiment;KLF6 morpholino oligonucleotides was microinjected into the Tg(lfabp:eGFP) transgenic zebrafish embryos.The morphant phenotype of the liver was imaged and the protein expression of KLF6 after knockdown of KLF6 was analyzed by Immunofluorescence staining.Results The expression of KLF6 in L-02 was significantly higher than in HepG2.After knockout of KLF6, KLF6 protein expression and apoptosis were significantly reduced.In addition, the cell cycle mainly stated in S phase and the migration ability of HepG2 was enhanced.After klf6 knockdown in transgenic zebrafish larvae, the development of zebrafish liver was delayed and KLF6 expression was obviously decreased in the liver.Conclusions The reduction of KLF6 expression increased the proliferation and migration ability, and reduced the apoptosis of HepG2.Loss of KLF6 affects the development of zebrafish liver, which may open a possibility to use zebrafish as a liver cancer model and for anti-liver cancer drug screening.

Objective To evaluate the effects of astragalus on liver injury and TGF-β1 mRNA expression in immature rats with obstructive jaundice(OJ).Methods Forty immature male Wistar rats were randomly divided into a control,a shamoperation,an OJ,and an OJ+A groups.Wistar rats in the OJ and OJ+A group were subjectedto common bile duct ligation(CBDL),while the sham group had the bile duct mobilized but not tied.The control,sham,and OJ groups were giyen 0.5ml of normal saline by intrapedtoneal injection daily.In the OJ+A group,250mg/100g body weight of astragalus injection was applied intraperitoneally daily from day 1 to 7 of the study.All animals were sacrificed on postoperative day 8.Liver tissue and peripheral blood were colleered.Serum Alanine aminotransferase(ALT),Aspartate aminotransferase(AST),and total cholic acid(TCA)level were detected.Hepatic morphological findings were observed by light microscopy.TGF-β1 mRNA were extracted from liver and measured by reverse transcription polymerase chain reaction(RT-PCR).Data were analyzed using chi-square test and student's test(-x±s),P＜0.05 was considered statistical significance.Results ①Serum AST,ALT,and TCA value in each OJ group were significantly higher than that of the control and sham operation groups.②In the control and sham operation group,normal structure of the liver remained,but in the OJ group,obvious degeneration of hepatocytes was detected,such as cholastasis,starch accumulation and fatty degeneration.Kupffer cells and dilated Disse'space were common in the OJ group.In the OJ group.histopathologic findings of the liver demonstrated intense degree of fibrosis,but in the OJ+A group.typical changes of large duct obstruction were significantly improved after astragalus injection treatment.③The TGF-β1 mRNA over-expression in the OJ group was seen compared with the control and the OJ+A groups.Conclusion ①In growing rat model of experimental obstructive jaundice,hepatic morphology and liver biochemical tests altered significantly.②The administration of astragaius can ameliorate liver damage and diminish expression of TGF-β1 mRNA of hepatic tissue,thus administration of astragalus may be effective in preventing hepatic injury in growing rats with obstructive jaundice.

PurposeTo investigate whole-body magnetic resonance imaging in diagnosis of idiopathic inflammatory myopathy (IIM), and to guide clinical treatment.Materials and Methods Twenty-six patients clinically diagnosed IIM including 19 dermatomyositis and 7 polymyositis were analyzed retrospectively. Whole-body MRI was performed in all patients including whole-body coronal scan and axial scan of both sides of thigh. Short tau inversion recovery (STIR) sequences were used in the coronal scan and T1WI and fat-suppressed T2WI were performed in the axial scan. Ten healthy volunteers were recruited as control group. MRI findings were compared between the two groups.Results Whole body MRI showed that muscles were homogeneously low signal intensity in the control group. Imaging findings of the patients with IIM included muscle inflammation, fascitis, subcutaneous tissue edema, muscle atrophy and fatty infiltration. The most common distribution site of muscle inflammation of dermatomyositis patients was thigh (n=18), followed by gluteus (n=14), great psoas muscle (n=13), shoulder muscles (n=11), leg muscle (n=11), erector spinae (n=10) and neck muscles (n=9). Findings out of muscles included cavities in the both lungs, infarction in femurs and tibias, avascular necrosis of femoral head, adrenal mass and thyroid nodules. The most common distribution site of muscle inflammation of polymyositis was thigh (n=5), followed by gluteus (n=3), great psoas muscle (n=3), shoulder muscles (n=2), leg muscles (n=2), erector spinae (n=1) and neck muscles (n=1). Findings out of muscles included 1 case of infarction in femurs and tibias.Conclusion Whole-body MRI can not only comprehensively evaluate the activity of IIM but also detect complications such as bone infarction. It's a powerful tool for diagnosis, guiding treatment and monitoring of IIM.

Abstract A suspected case of cutaneous anthrax was reported by Gongliu County Disease Control and Prevention Center, Ili Kazak Autonomous Prefecture, Xinjiang Uygur Autonomous Region on August 19, 2021. Then, an epidemiological survey was performed by a joint investigation team consisting of professionals from Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention, intermediate-level trainees from the Field Epidemiology Training Program of Chinese Center for Disease Control and Prevention, and professionals from Ili Kazak Autonomous Prefecture Center for Disease Control and Prevention. A total of 11 cutaneous anthrax cases were identified, including 8 suspected cases and 3 clinically diagnosed cases, and all cases were villagers in Y Village, X Township, Gongliu County, without severe case or deaths found. The onset of the first case occurred on July 27, and the onset of the last case occurred on August 16. The main clinical manifestations included ulcerative eschar on hands and exposed skin of the upper extremity. A Bacillus anthracis isolate was detected in meat samples from infected cattle. Epidemiological surveys showed that villagers did not report infected cattle to related sectors and privately slaughtered and ate meat from infected cattle without any effective protective measures, resulting in this outbreak. It is recommended to strengthen health education for people raising, selling and slaughtering livestock, and publicize zoonotic disease control knowledge, including anthrax, and establish an effective surveillance and response system for anthrax for immediate identification and treatment of epidemics.

OBJECTIVETo study the effect of Panax notoginseng saponins (PNS) on expression of alpha-aecretase mRNA in the brains of senescence-accelerated SAMP8 mice.

METHODSAMP8 mice were randomly divided into the control group, the PNS high-dosage group (200 mg x kg(-1)), the PNS low-dosage group (100 mg x kg(-1)) and the huperzine A group (0.3 mg x kg(-1)), with eight mice in each group. The control group and each administration group were orally administered with the same volume of double distilled water once for consecutively two months. The expression of alpha-secretase (ADAM 9, ADAM10, ADAM17) mRNA was assayed by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR).

RESULTThe expression of ADAM9 mRNA in PNS high-dosage group and huperzine A group were significantly higher than that of the control group (P < 0.05). The expression of ADAM10 in the PNS high-dosage group, the PNS low-dosage group and the huperzine A group showed no significant difference from the control group.

CONCLUSIONPNS can up-regulate expressions of ADAM9 mRNA and down-regulate expressions of ADAM10 mRNA in the brains of SAMP8 mice.

ADAM Proteins ; genetics ; ADAM10 Protein ; Alzheimer Disease ; drug therapy ; metabolism ; Amyloid Precursor Protein Secretases ; genetics ; Animals ; Disease Models, Animal ; Gene Expression Regulation, Enzymologic ; drug effects ; Membrane Proteins ; genetics ; Mice ; Panax notoginseng ; RNA, Messenger ; analysis ; Saponins ; pharmacology

Background Hyperuricemia is frequently present in patients with heart failure. Many pathological conditions, such as tissue ischemia, renal function impairment, cardiac function impairment, metabolic syndrome, and inflammatory status, may impact uric acid (UA) metabolism. This study was to assess their potential relations to UA metabolism in heart failure. Methods We retrospectively assessed clinical characteristics, echocardiological, renal, metabolic and inflammatory variables selected on the basis of previous evidence of their involvement in cardiovascular diseases and UA metabolism in a large cohort of randomly selected adults with congestive heart failure (n = 553). By clustering of indices, those variables were explored using factor analysis. Results In factor analysis, serum uric acid (SUA) formed part of a principal cluster of renal functional variables which included serum creatinine (SCr) and blood urea nitrogen (BUN). Univariate correlation coefficients between variables of patients with congestive heart failure showed that the strongest correlations for SUA were with BUN (r = 0.48, P < 0.001) and SCr (r = 0.47, P < 0.001). Conclusions There was an inverse relationship between SUA levels and measures of renal function in patients with congestive heart failure. The strong correlation between SUA and SCr and BUN levels suggests that elevated SUA concentrations reflect an impairment of renal function in heart failure.

Objective:To assess the changes of left ventricular systolic function and global synchronization and myocardial work in patients with left bundle branch pacing (LBBP) by two-dimensional multi-layered speckle tracking imaging.Methods:Forty-two patients with Ⅱ degree Ⅱ type or Ⅲ degree atrioventricular block (AVB) in the Cardiovascular Hospital of Xiamen University from April to December 2019 were selected as pacing group, which were further divided into two groups according to different pacemaker modes: twenty patients with right ventricular septal pacing (RVSP), twenty-two patients with LBBP, and twenty patients with normal ECG and cardiac structure were enrolled as control group. Echocardiography of pacing group and control group was performed and analyzed. The left ventricular subendocardial longitudinal strain peak(LSendo), the middle layer myocardial longitudinal strain peak(LSmid), subepicardial longitudinal strain peak(LSepi), global myocardial longitudinal strain peak(GLS), peak strain dispersion (PSD), global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) were acquired. The differences among the three groups were analyzed and the high difference indexes were screened by statistical modeling.Results:LSendo in three groups had no difference ( P>0.05). LSmid, LSepi, GLS in the control group, LBBP group and RVSP groups were decreased gradually ( P<0.05). GLS in LBBP group was higher than in RVSP group ( P<0.05). Compared with the control group, the increases of QRS and PSD in LBBP group were not statistically significant ( P>0.05), while the decreases of QRS and PSD in LBBP group were statistically significant compared with the RVSP group ( P<0.05). The values of GCW among three groups had no statistical significance ( P>0.05). Compared with the control group, the decrease of GWI in LBBP group was not statistically significant ( P>0.05), while the increase of GWW and the decrease of GWE were statistically significant ( P<0.05). Compared with the RVSP group, the increases of GWI and GWE and the decrease of GWW in LBBP group were statistically significant ( P<0.05). QRS, LSendo, GLS, LSmid, left ventricular apex rotation to basal rotation peak time(ApexBase period) were the indexes with significant difference among LBBP and RVSP groups and all index characteristics showed better in LBBP than RVSP group. Conclusions:Two-dimensional multi-layered speckle tracking imaging can be used to evaluate the effect of LBBP on left ventricular systolic function and global synchronization and myocardial work. LBBP longitudinal mechanical synchronization is better than right ventricular septal pacing by improving the peak global myocardial longitudinal strain and myocardial work after pacemaker.

Objective:To investigate the values of two-dimensional and three-dimensional echocardiographic parameters in predicting pulmonary vascular resistance (PVR) in chronic pulmonary thromboembolic pulmonary hypertension (CTEPH).Methods:A total of 141 patients diagnosed with CTEPH in China-Japan Friendship Hospital from November 2015 to December 2022 were included. Two-dimensional echocardiographic indicators reflecting PVR were constructed according to the calculation formula of PVR: echocardiographic estimated systolic pulmonary artery pressure (sPAP Echo)/left ventricular end-diastolic diameter (LVIDd), echocardiographic estimated mean pulmonary artery pressure (mPAP Echo)/LVIDd. sPAP Echo/left ventricular end-diastolic volume (LVEDV), sPAP Echo/left ventricular cardiac output (LVCO) were measured by three-dimensional echocardiography. The correlations between two-dimensional and three-dimensional echocardiographic ratios and invasive PVR were then analyzed using the Spearman correlation method. Using receiver operating characteristic curve analysis, cut-off values for the ratios were generated to identify patients with PVR>1 000 dyn·s -1·cm -5. Pre- and postoperative hemodynamics and echocardiographic data were analyzed, as well as the correlation between the reduction rate of the echocardiographic index and PVR in 54 patients who underwent pulmonary endarterectomy (PEA). Results:sPAP Echo/LVIDd, sPAP Echo/LVEDV and sPAP Echo/LVCO were moderately correlated with PVR( rs=0.62, 0.52, 0.63, both P<0.001). The ratio of sPAP Echo to LVEDV, when greater than or equal to 1.41, had a sensitivity of 0.800 and a specificity of 0.930 for determining PVR >1 000 dyn·s -1·cm -5 (AUC=0.860, P<0.001). Similarly, the ratio of sPAP Echo to LVIDd, when greater than or equal to 2.14, had a sensitivity of 0.647 and a specificity of 0.861 for determining PVR >1000 dyn·s -1·cm -5 (AUC=0.830, P<0.001). The sPAP Echo/LVIDd and mPAP Echo/LVIDd significantly decreased after PEA (both P<0.001). The sPAP Echo/LVIDd and mPAP Echo/LVIDd reduction rate (ΔsPAP Echo/LVIDd and ΔmPAP Echo/LVIDd) were significantly correlated with PVR reduction rate (ΔPVR), respectively ( rs=0.61, 0.63, both P<0.05). Conclusions:Two-dimensional ratio sPAP Echo/LVIDd and three-dimensional ratio sPAP Echo/LVEDV can be used to noninvasively estimate PVR in CTEPH patients. The conventional ratio sPAP Echo/LVIDd is convenient and reproducibly suitable for monitoring the improvement of PVR before and after treatment, and its ratio of 2.14 can predict the significant increase of PVR in CTEPH patients (>1 000 dyn·s -1·cm -5).