Fermented Cordyceps Powder Combined with ACEI/ARB in Treatment of Diabetic Kidney Disease： A Systematic Review / 中国实验方剂学杂志

［Abstract］Objective:To evaluate the efficacy and safety of fermented cordyceps powder combined with angiotensin-converting enzyme inhibitors （ACEI）/angiotensin Ⅱ receptor blocker （ARB） in the treatment of diabetic kidney disease （DKD）. Method:The randomized controlled trials （RCTs） concerning the treatment of DKD with fermented cordyceps powder plus ACEI/ARB were retrieved from Pubmed， Embase， Cochrane library， China National Knowledge Infrastructure （CNKI）， Chinese BioMedical Literature Database on disc （CBMdisc）， Wanfang Data Knowledge Service Platform， and Chongqing Weipu Database for Chinese Technical Periodicals （VIP）. The quality of the included articles was evaluated by the Cochrane Collaboration's tool， followed by data analysis using RevMan 5.3. Result:A total of 48 RCTs were included， involving 4 562 cases. As revealed by Meta-analysis， the effective rate of fermented cordyceps powder combined with ACEI/ARB was higher than that of ACEI/ARB ［risk ratio （RR）=1.20， 95% confidence interval （CI） （1.15，1.24）， <italic>P</italic><0.000 01］. Moreover， such combination effectively reduced urinary albumin excretion rate ［standardized mean difference （SMD）=-2.61，95%CI （-3.17，-2.05），<italic>P</italic><0.000 01］，24-h proteinuria［SMD=-1.75，95%CI （-2.15，-1.35），<italic>P</italic><0.000 01］， serum creatinine（Scr）［mean difference （MD）=-14.57，95%CI （-17.94，-11.21），<italic>P</italic><0.000 01］， blood urea nitrogen（BUN）［MD=-1.05，95%CI （-1.29，-0.81），<italic>P</italic><0.000 01］， cystatin C （Cys-C） ［MD=-0.52，95%CI （-0.68，-0.36），<italic>P</italic><0.000 01］， fasting blood glucose（FBG）［MD=-0.59，95%CI （-0.93，-0.25），<italic>P</italic>=0.000 6］， hemoglobin A1c（HbA1c）［MD=-0.50，95%CI（-0.75，-0.24），<italic>P</italic>=0.000 1］， tumor necrosis factor-<italic>α</italic>（TNF）-<italic>α </italic>［SMD=-1.68，95%CI （-2.21，-1.15），<italic>P</italic><0.000 01］， C-reactive protein（CRP） ［SMD=-1.35，95%CI （-1.77，-0.93），<italic>P</italic><0.000 01］， and interleukin-6 （IL-6） ［SMD=-1.52，95%CI （-1.98，-1.07），<italic>P</italic><0.000 01］. There was no significant difference in the incidence of adverse events between the two groups ［RR=0.77，95%CI （0.49，1.21），<italic>P</italic>=0.25］. Conclusion:Fermented cordyceps powder combined with ACEI/ARB is more effective than ACEI/ARB in the treatment of DKD， which is worthy of clinical promotion and use. More multi-center RCTs with a large sample size are needed for verification.

Depression Is Associated With Constipation in Patients With Parkinson's Disease.

Objective: Constipation is one of the most frequent non-motor symptoms (NMS) in Parkinson's disease (PD), causing great disturbance to patients. The present study investigated the prevalence and the clinical features of constipation in patients with PD and explored the difference between prodromal and clinical constipation of PD. Methods: A total of 186 patients with PD were recruited into this study. Subjective constipation was defined by ROME III criteria. Demographic and PD-related clinical information of the participants were collected. The PD patients were objectively assessed by a spectrum of rating scales of motor symptoms, non-motor symptoms, and quality of life. Results: In total, 51.61% (96/186) of PD patients suffer from constipation. Compared with patients without constipation, the patients with constipation were prone to have restless leg syndrome, depression, and anxiety and have higher scores of the non-motor symptoms scale. Among patients with constipation, 21.88% (21/96) patients had constipation in prodromal stage. Compared with patients with constipation in clinical stage, patients with prodromal constipation had a lower age of constipation onset (56.48 ± 9.63 and 65.26 ± 8.42, χ2 = 4.091, P < 0.001), longer timespan from constipation onset to motor symptom onset (6.62 ± 3.91 and 3.18 ± 2.13, χ2 = -3.877, P = 0.001). Patients with prodromal constipation were predominantly tremor onset (χ2 = 4.405, P = 0.044) and usually had a better quality of life [28 (14.50-37.5) and 40 (25.0-55.0), χ2 = 2.011, P = 0.046]. Depression was the only risk factor of constipation in PD patients. Body mass index, depression, and anxiety were factors that affected the life quality in patients with constipation. Conclusions: Our results supported the high incidence of constipation in patients with PD and that, in some patients, constipation occurred before the onset of motor symptoms. The specific clinical characteristics of patients with constipation and with prodromal constipation help to make early diagnosis, to discover the relationship between constipation and PD, and to further explore the pathogenesis of this degenerative disease.

Optimization of synthetic pathway and fermentation process of yeast cell factories for production of oleanoic acid / 中国中药杂志

<p><b>OBJECTIVE</b>To optimize the synthetic pathway and fermentation process of yeast cell factories for production of oleanoic acid.</p><p><b>METHOD</b>Using the DNA assembler method, one copy of Glycyrrhiza glabra beta-amyrin synthase (GgbAS), Medicago truncatula oleanolic acid synthase (MtOAS) and Arabidopsis thaliana cytochrome P450 reductase 1 (AtCPR1) genes were introduced into Saccharomyces cerevisiae strain BY-OA, resulting in strain BY-20A. YPD medium with different glucose concentration were then used to cultivate strain BY-2OA.</p><p><b>RESULT</b>Increasing gene copies of GgbAS, MtOAS and AtCPR1 resulted in increased beta-amyrin and oleanolic acid production. The strain BY-2OA produced 136.5 mg x L(-1) beta-amyrin and 92.5 mg x L(-1) oleanolic acid, which were 54% and 30% higher than the parent strain BY-OA. Finally, the titer of oleanolic acid increased to 165.7 mg x L(-1) when cultivated in YPD medium with 40 mg x L(-1) glucose.</p><p><b>CONCLUSION</b>Production of oleanoic acid increased significantly in the yeast strain BY-2OA, which can provide the basis for creating an alternative way for production of oleanoic acid in place of extraction from plant sources.</p>

Construction of Saccharomyces cerevisiae cell factories for lycopene production / 中国中药杂志

For microbial production of lycopene, the lycopene synthetic genes from Pantoea agglomerans were integrated into Saccharomyces cerevisiae strain BY4742, to obtain strain ZD-L-000 for production of 0.17 mg · L(-1) lycopene. Improving supplies of isoprenoid precursors was then investigated for increasing lycopene production. Four key genes were chosen to be overexpressed, inclu- ding truncated 3-hydroxy-3-methylglutaryl-CoA reductase gene (tHMG1), which is the major rate-limiting enzyme in the mevalonate (MVA) pathway, a mutated global regulatory factor gene (upc2.1), a fusion gene of FPP synthase (ERG20) and endogenous GGPP synthase (BTS1), which is a key enzyme in the diterpenoid synthetic pathway, and GGPP synthase gene (SaGGPS) from Sulfolobus acidocaldarius. Over-expression of upc2.1 could not improve lycopene production, while over-expression of tHMGI , BTS1-ERG20 and SaGGPS genes led to 2-, 16. 9- and20. 5-fold increase of lycopene production, respectively. In addition, three effective genes, tHMG1, BTS1-ERG20 and SaGGPS, were integrated into rDNA sites of ZD-L-000, resulting in strain ZD-L-201 for production of 13.23 mg · L(-1) lycopene, which was 77-fold higher than that of the parent strain. Finally, two-phase extractive fermentation was performed. The titer of lycopene increased 10-fold to 135.21 mg · L(-1). The engineered yeast strains obtained in this work provided the basis for fermentative production of lycopene.

Antagonistic effect of atipamezole, flumazenil and naloxone following anaesthesia with xylazine, tramadol and tiletamine/zolazepam combinations in pigs.

OBJECTIVE: To evaluate the antagonistic effects of atipamezole (ATI), flumazenil (FLU) and naloxone (NAL) alone and in various combinations following administration of tiletamine-zolazepam-xylazine-tramadol. STUDY DESIGN: Prospective, experimental, randomized cross-over study. ANIMALS: Eight Chinese miniature pigs (three females and five males) mean age 8 (range 7-10) months and bodyweight 57.5 (52.4-62.1) kg. METHODS: All animals were anaesthetized with tiletamine/zolazepam (3.0 mg kg(-1)), xylazine (1.2 mg kg(-1)) and tramadol (1.6 mg kg(-1)) given intramuscularly (IM). Thirty minutes later, one of eight treatments was administered IM: saline control, ATI (0.12 mg kg(-1)), FLU (0.1 mg kg(-1)), NAL (0.03 mg kg(-1)), ATI-FLU, FLU-NAL, ATI-NAL or ATI-FLU-NAL. After injection of antagonists the following times were recorded: to recovery of the palpebral, pedal and tail clamp reflexes, to head movement, sternal recumbency, standing and walking. Posture, sedation, analgesia, jaw relaxation and auditory response were scored at set times until 120 minutes after injection of antagonists. Heart rates, respiratory rates and rectal temperature were measured at those times. Data were analyzed by anova for repeated measures, followed by the Tukey's test to compare differences between means, or by Kruskal-Wallis test as appropriate. RESULTS: FLU, NAL alone, or FLU-NAL did not effectively antagonize anaesthesia induced by tiletamine/zolazepam-xylazine-tramadol. ATI, ATI-FLU, ATI-NAL and ATI-FLU-NAL produced an immediate and effective recovery from anaesthesia. The combination of ATI-FLU-NAL was the most effective combination in antagonizing the anaesthetic effect. Adverse effects such as tachycardia, tachypnoea, excitement and muscle tremors were not observed during this study. CONCLUSION AND CLINICAL RELEVANCE: ATI-FLU-NAL is the most effective combination for antagonizing tiletamine/zolazepam-xylazine-tramadol anaesthesia in pigs. However, ATI alone or in various combinations also provides effective antagonism.

Clinical analysis of chronic cardiac insufficiency with anaemia / 中国地方病学杂志

Objective To find the effective therapeutic arrangement through investigating the clinical characteristics of chronic cardiac insufficiency with anaemia. Methods A total of 46 cases of anemia from 315patients who had been admitted to department of cardiology, the First Affiliated Hospital, Harbin Medical University for chronic cardiac insufficiency with anaemia were selected. They were divided into two groups. There were 22 patients in the first group who only accepted treatment to improve cardiac function (normal cardiac, diuretic,vasodilator therapy, etc.), and 24 patients in the second group who accepted treatment to improve cardiac function while receiving anti-anemia therapy treatment, oral ferrous sulfate tablets(0.3 g/tablet), 1 tablet each time, 3 times a day and(or) 2 times per week subcutaneous erythropoietin 3000 U. The hemoglobin(Hb), red blood cell(RBC) ,hematocrit (HCT), left ventricular ejection fraction (LVEF), fractional shortening (FS), stroke volume (SV) , cardiac output(CO) and E peak and A peak ratio(E/A) were observed before and after treatment. By logistic regression, grade grade Ⅱ , Ⅲ , Ⅳ, the incidence of anaemia were 7.9% (10/126), 19.2% (23/120) and 24.6% (17/69),respectively. Grade Ⅱ compared with grades Ⅲ, Ⅳ, the difference was statistically significant (x2 = 4.08, 3.12, all (3.49 ± 0.17) × 1012/L, (0.36 ± 0.08)%, (48.9 ± 3.11)%, (15.6 ± 1.8)%, (38.9 ± 3.7)%, (4.4 ± 1.6)% and (130.7 ±5.75)g/L, (4.12 ± 0.25) × 1012/L, (0.43 ± 0.02)%, (58.5 ± 2.65)%, (18.0 ± 2.5)%, (49.1 ± 7.7)%, (5.1 ± 1.2)%in the first and second groups, respectively. The difference between the two groups was statistically significant(t =value of Hb, RBC, HCT, LVEF, FS,SV, CO were (102.7 ± 6.93)g/L, (3.41 ± 0.12) × 1012/L, (0.35 ± 0.07)%,(47.5 ± 2.86)%, (16.0 ± 2.4)%, (38.2 ± 7.9)%, (3.7 ± 1.4)%, respectively. Compared with those after treatment,the difference was statistically significant (t = 15.632, 13.325, 5.569, 17.182, 3.186, 2.999, 3.074, all P ＜ 0.05);Ⅳ-level relative risk were 1.62, 3.14(P ＜ 0.05 or ＜ 0.01) . Conclusions Based on the standard treatment with treatment of anemia, cardiac contractile function can be improved.

Coronary artery and myocardium lesion comparison post atrioventricular ring radiofrequency catheter ablation with different catheters / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analyze the extent of myocardium and coronary artery lesion post atrioventricular ring radiofrequency catheter ablation with different tip catheters.</p><p><b>METHODS</b>Twenty-one healthy dogs were randomly divided into 64 degrees C/50 W/100 s, 64 degrees C/100 W/100 s, 45 degrees C/45 W/100 s groups and ablated by 4 mm tip catheter, 8 mm tip catheter and irrigated tip catheter respectively. Left atrioventricular ring and right atrioventricular ring ablation were performed in all dogs. After ablation, myocardium lesion volume was calculated as 1/6pi x length x width x depth. Histological examinations were performed at the myocardium tissue at ablation sites.</p><p><b>RESULTS</b>The lesion depths post 8 mm tip catheter ablation (7.18 +/- 1.72) mm and irrigated tip catheter ablation (7.99 +/- 1.77) mm were similar and significantly deeper than that post 4 mm tip catheter ablation (4.54 +/- 1.38) mm, P < 0.01. Similar results were found in terms of lesion volume [(356.76 +/- 94.44) mm(3) post 8 mm tip catheter ablation, (391.69 +/- 109.54) mm(3) post irrigated tip catheter ablation and (191.34 +/- 74.52) mm(3) post 4 mm tip catheter ablation]. Five (5/42, 11.9%) transmural myocardium necrosis and 8 (8/42, 19%) coronary artery lesions were observed post ablations.</p><p><b>CONCLUSION</b>The extents of post ablation myocardium and coronary artery lesion were significantly higher induced by 8 mm tip catheter and irrigate tip catheter compared those by 4 mm tip catheter.</p>

Pathologic observation on ventricu lar myocardium of epicardium and focus underneath atrioventricularring produced by microwave catheter ablation / 中国地方病学杂志

Objective To observe the variation of enzymatic activity and areas and bulk of focus of heart injuries by using controllable catheter to ablate epicardial tmsue of rabbits and focus underneath atrioventrieular ring narcosis with 20% urethane(4 ml/kg)and divided into three groups.Each group included 7 rabbits.Anterior wallepieardium of left ventricle was ablated thirty seconds in each group(10,20 and 30 W)with self-made ablationspheroid microwave antenna,refilling with high pressure normal saline at same time.Then all of the rabbits were sacrificed respectively and their ventricular myocardium were taken out to undergo immunohistochemistry in order to display suceinate dehydrogenase(SDH).Also amplitude Wag measured in order to calculate areas of heart injuries.(8F)wag delivered to the pre-selected sites around atrioventricular ring of thirty-two healthy dogs,which had beenin intravenous narcosis with pentobarbital sodium(30 mg/kg).The dogs were divided into four groups(40,50,60 and 80 w) and two time points(60 and 120 s),by the combined method of X-ray and endocardial electrocardiograph,the microwave antenna could be confirmed to be located at the accurate position between anterior and posterior wall close to septum of left/right ventricle.After ventricular myocardium had been taken out,amplitude were measuredin order to calculate bulk of heart injuries by 1/6×3.14 x long×wide×deep.In addition.the histological changesand transmural injury were examined by optic microscope.Results In each group,the centre of injuries wagenzyme deficiency locus.The diameter and areag of heart injuries enlarged significantly(3.99.±0.41),(5.20±0.25),(6.31±0.37)mm and(12.53±2.56),(21.19±3.14),(30.96±3.76)mm2 with the increased microwave power level(10、20、30 W).Group comparison had statisficM significance(F＝76.8,58.5;P＜0.01 or ＜0.05).A total of 116points were ablated.The myocardial lesion showed ellipse in shape,and continuous symmetrical coagulationnecrosis under microscopic examination.There was a clear demarcated line around tlle myocardial tissue and fewparietal thmmbus.There were 16 transmura]injuries and five-with lung damage.The bulk of lesion aroundatrioventrieular ring hag been significantly enlarged(46.7±2.5),(51.1±2.7),(133.2±3.4),(141.8±3.9),(248.5±6.2),(260.3±6.5),(313.7±9.5),(327.4±10.5)with the increased microwave power level(40,50,60and 80 W)and/or distance of microwave ablation(60 and 120 s).Groups comparison had statistical significance(F＝31.16,27.85;all P＜0.01).In each time point,the lesion bulks had conspicuous distinction of statistics.In the same microwave power,the time wag longer,the bulk was larger(P＜0.01).Conclusions The more the microwave power level and time,the severe the heart injuries is.It is possible to use the microwave energy to ablate the deep focus under endocardium around atrioventricular ring.

Study on the pathological change and the expression of neuron specific enolase in the hippocampus dentategyrus granular cell layer of epilepsy patients / 中国地方病学杂志

Objective To find out pathologieal change and the expression of neuron specific enolage (NSE)in the hippocampus dentate gyrus granular cell layer of epilepsy patients,to investigate the relationship between the pathological change and the cause of the epilepsy.Methods The specimens of hippocampus were from 9 epilepsy patients and 20 normal persons and the pathological change were investigated under the staining of the hematoxylin and eosin staining.The expression of NSE in the hippocampns denmte gyrus granular cell layer of epilepsy patients was detected by immunohistochemistry(IHC)with specific antibody,and the rate of NSE positive nenrons was evaluated.Results The nuclear pyknosis was observed in all of hippocampus from the epilepsy patients and some neurons were swelling.The positive of NSE was showed to have yellow granule;the rate of NSE positive was 28.66%.The expression of NSE of the neurons in the hippocampus dentate gyrus granular cell layer was.significantly reduced in epilepsy patients(7.9±5.6)%.The normal neuron nuclear was big and round in the middle of the cell and the nucleolus could be seen easily.The expression of NSE of the neurons in the hippocampus dentate gyrus granular cell layer was(39.0±17.4)%.Compared with normal group,the number of neurons with yellow granule was reduced.The difference of the NSE expression rate between the two group was statistically significant(t＝-5.13,P＜0.01).Conclusions The result suggests that the pathological abnormality and the reduced expression of NSE on the hippocampus dentate gyrus granular cell layer neurons could be one of the main reasons of the occurring of epilepsy.