Acute Developmental Toxicity of Panax notoginseng in Zebrafish Larvae / 中国结合医学杂志

OBJECTIVE@#To evaluate toxicity of raw extract of Panax notoginseng (rPN) and decocted extract of PN (dPN) by a toxicological assay using zebrafish larvae, and explore the mechanism by RNA sequencing assay.@*METHODS@#Zebrafish larvae was used to evaluate acute toxicity of PN in two forms: rPN and dPN. Three doses (0.5, 1.5, and 5.0 µ g/mL) of dPN were used to treat zebrafishes for evaluating the developmental toxicity. Behavior abnormalities, body weight, body length and number of vertebral roots were used as specific phenotypic endpoints. RNA sequencing (RNA-seq) assay was applied to clarify the mechanism of acute toxicity, followed by real time PCR (qPCR) for verification. High performance liquid chromatography analysis was performed to determine the chemoprofile of this herb.@*RESULTS@#The acute toxicity result showed that rPN exerted higher acute toxicity than dPN in inducing death of larval zebrafishes (P<0.01). After daily oral intake for 21 days, dPN at doses of 0.5, 1.5 and 5.0 µ g/mL decreased the body weight, body length, and vertebral number of larval zebrafishes, indicating developmental toxicity of dPN. No other adverse outcome was observed during the experimental period. RNA-seq data revealed 38 genes differentially expressed in dPN-treated zebrafishes, of which carboxypeptidase A1 (cpa1) and opioid growth factor receptor-like 2 (ogfrl2) were identified as functional genes in regulating body development of zebrafishes. qPCR data showed that dPN significantly down-regulated the mRNA expressions of cpa1 and ogfrl2 (both P<0.01), verifying cpa1 and ogfrl2 as target genes for dPN.@*CONCLUSION@#This report uncovers the developmental toxicity of dPN, suggesting potential risk of its clinical application in children.

Positive inotropic effect of phosphodiesterase type 9 inhibitor PF-04449613 in rats and its underlying mechanism / 生理学报

This study aimed to explore the positive inotropic effect of phosphodiesterase type 9 (PDE9) inhibitor PF-04449613 in ratsand its cellular and molecular mechanisms. The heart pressure-volume loop (P-V loop) analysis was used to detect the effects of PF-04449613 on rat left ventricular pressure-volume relationship, aortic pressures and peripheral vessel resistance in healthy rats. The Langendorff perfusion of isolated rat heart was used to explore the effects of PF-04449613 on heart contractility. The cardiomyocyte sarcoplasmic reticulum (SR) Ca

Application of the Virtual Reality-Pattern Visual Evoked Potential in Forensic Visual Acuity Evaluation / 法医学杂志

Objective To explore a kind of visual evoked potential test equipment and method that is more suitable for the application of forensic clinical visual acuity evaluation. Methods Thirty-four volunteers （68 eyes） were selected, including 15 males and 19 females, aged between 20 and 40 years. Test lenses were placed before the tested eyes of volunteers to induce refractive myopia with insert method, and the diopter lenses were adjusted so that the visual acuity level of one eye of volunteers was above 0.8, and the visual acuity of the other eye was at moderate damage level （<0.3 and ≥0.1）. The tests were carried out under the binocular simultaneous asynchronous stimulation mode （hereinafter referred to as "binocular mode"） and monocular separate stimulation mode （hereinafter referred to as "monocular mode"） of virtual reality-pattern visual evoked potential （VR-PVEP）, and the amplitude of PVEP of volunteers under the two modes was compared at four spatial frequencies of 8×8, 16×16, 24×24 and 32×32. Results The differences in the amplitude of P100 wave between monocular and binocular modes at 8×8 spatial frequency had no statistical significance and the differences in amplitude of P100 wave between monocular and binocular modes at 16×16, 24×24, and 32×32 spatial frequencies had statistical significance （P<0.05）. The amplitude of the same eye in monocular mode was higher than that in binocular mode. Through correlation analysis, it was found that the amplitude of P100 wave in monocular mode was moderately correlated with amplitude of P100 wave in binocular mode. Conclusion In forensic identification practice, VR-PVEP is helpful for overcoming the disturbance of poor fixation, and to increase the reliability of PVEP evaluation results. It can greatly shorten the detection time of PVEP and improve work efficiency.

Appropriate Use of Non-steroidal Anti-inflammatory Drugs during the Perioperative Period: a Retrospective Multicenter Study / 中国药学杂志

OBJECTIVE: To evaluate the appropriateness of nonsteroidal anti-inflammatory drugs (NSAIDs) used in the perioperative period. METHODS: This was a retrospective multicenter study with three stages: ①characterization of the application of NSAIDs through questionnaires; ②establishment of an expert group and development of the standard for prescription evaluation; ③random enrollment of cases using NSAIDs during the perioperative period from October 2016 to March 2017 and evaluation of prescriptions. RESULTS: The study was conducted in 16 tertiary-care hospitals and included 960 cases. NSAIDs were commonly used in 15 hospitals (93.8%) during the perioperative period. Flurbiprofen axetil injection, parecoxib sodium injection and celecoxib capsule were NSAIDS with the top three expenses. Ten (62.5%) hospitals did not routinely intervene for the irrational use of NSAIDs, and only two (12.5%) hospitals established the regulatory regime of NSAIDs.The overall irrational rate was 23.3% (n=224). Too long continuous medication duration and inappropriate combination of NSAIDs were the main problems, involving 98 cases (10.2%) in 10 hospitals and 76 cases (7.9%) in 11 hospitals, respectively. Other problems were: 26 cases (2.7%) used drugs beyond contraindication, and 24 cases (2.5%) administrated drugs in irrational route.CONCLUSION: NSAIDs are widely used in the perioperative period. Lack of regulatory regime, insufficient clinical intervention and irrational prescriptions are the current status of NSAIDs usage. Therefore, it is necessary to take powerful measures and effective pharmaceutical intervention to improve the use of NSAIDs.

A 3.06-Mb interstitial deletion on 12p11.22-12.1 caused brachydactyly type E combined with pectus carinatum / 中华医学杂志(英文版)

Background@#Brachydactyly, a developmental disorder, refers to shortening of hands/feet due to small or missing metacarpals/metatarsals and/or phalanges. Isolated brachydactyly type E (BDE), characterized by shortened metacarpals and/or metatarsals, consists in a small proportion of patients with Homeobox D13 (HOXD13) or parathyroid-hormone-like hormone (PTHLH) mutations. BDE is often accompanied by other anomalies that are parts of many congenital syndromes. In this study, we investigated a Chinese family presented with BDE combined with pectus carinatum and short stature.@*Methods@#A four-generation Chinese family was recruited in June 2016. After informed consent was obtained, venous blood was collected, and genomic DNA was extracted by standard procedures. Whole-exome sequencing was performed to screen pathogenic mutation, array comparative genomic hybridization (Array-CGH) analysis was used to analyze copy number variations, and quantitative real-time polymerase chain reaction (PCR), stride over breakpoint PCR (gap-PCR), and Sanger sequencing were performed to confirm the candidate variation.@*Results@#A 3.06-Mb deletion (chr12:25473650–28536747) was identified and segregated with the phenotype in this family. The deletion region encompasses 23 annotated genes, one of which is PTHLH which has been reported to be causative to the BDE. PTHLH is an important regulator of endochondral bone development. The affected individuals showed bilateral, severe, and generalized brachydactyly with short stature, pectus carinatum, and prematurely fusion of epiphyses. The feature of pectus carinatum has not been described in the PTHLH-related BDE patients previously.@*Conclusions@#The haploinsufficiency of PTHLH might be responsible for the disease in this family. This study has expanded the knowledge on the phenotypic presentation of PTHLH variation.

A 3.06-Mb interstitial deletion on 12p11.22-12.1 caused brachydactyly type E combined with pectus carinatum / 中华医学杂志(英文版)

BACKGROUND@#Brachydactyly, a developmental disorder, refers to shortening of hands/feet due to small or missing metacarpals/metatarsals and/or phalanges. Isolated brachydactyly type E (BDE), characterized by shortened metacarpals and/or metatarsals, consists in a small proportion of patients with Homeobox D13 (HOXD13) or parathyroid-hormone-like hormone (PTHLH) mutations. BDE is often accompanied by other anomalies that are parts of many congenital syndromes. In this study, we investigated a Chinese family presented with BDE combined with pectus carinatum and short stature.@*METHODS@#A four-generation Chinese family was recruited in June 2016. After informed consent was obtained, venous blood was collected, and genomic DNA was extracted by standard procedures. Whole-exome sequencing was performed to screen pathogenic mutation, array comparative genomic hybridization (Array-CGH) analysis was used to analyze copy number variations, and quantitative real-time polymerase chain reaction (PCR), stride over breakpoint PCR (gap-PCR), and Sanger sequencing were performed to confirm the candidate variation.@*RESULTS@#A 3.06-Mb deletion (chr12:25473650-28536747) was identified and segregated with the phenotype in this family. The deletion region encompasses 23 annotated genes, one of which is PTHLH which has been reported to be causative to the BDE. PTHLH is an important regulator of endochondral bone development. The affected individuals showed bilateral, severe, and generalized brachydactyly with short stature, pectus carinatum, and prematurely fusion of epiphyses. The feature of pectus carinatum has not been described in the PTHLH-related BDE patients previously.@*CONCLUSIONS@#The haploinsufficiency of PTHLH might be responsible for the disease in this family. This study has expanded the knowledge on the phenotypic presentation of PTHLH variation.

Roles of mitochondria-associated endoplasmic reticulum membranes in ischemic stroke / 中国药理学通报

Mitochondria-associated endoplasmic reticulum membranes (MAM) provide an excellent scaffold for crosstalk between ER and mitochondria, which play an important role in Ca2+ homeostasis, oxidative stress, inflammation, mitochondrial morphological and functional regulation, lipid metabolism, apop-tosis, autophagy and other processes. With the in-depth research, the function of MAM and the pathophysiological mechanisms of ischemic stroke overlap highly. On the other hand, a variety of drugs or compounds protect against ischemic stroke by affecting MAM-related proteins. In this review, we summarize the critical role of MAM in ischemic stroke and the potential of MAM as one drug target for treating ischemic stroke.

Total flavonoids of bugloss limits left ventricular remodeling after myocardial infarction in mice / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effects of total flavonoids of bugloss(TFB)on left ventricular (LV)remodeling after myocardial infarction(MI),LV size and function was compared in mice subjected to left anterior descending coronary artery ligation. METHODS 28 d after MI, the infarcted fraction of the LV and LV mass, systolic and diastolic function were measured. Capillary density and myocyte width in the nonischemic portion of the LV were also determined.RESULTS 28 d after MI,both groups had dilated LVs with decreased fractional shortening and lower ejection fractions. Although the infarcted size of the LV was similar in both groups,LV end-diastolic internal diameter,end-diastolic volume,and mass were lower, but fractional shortening, ejection fraction, and the maximum rate of developed LV pressure(dp/dtmax)were greater in TFB treated mice than in control mice.Impairment of diastolic func-tion, as measured by the time constant of isovolumic relaxation (t) and the maximum rate of LV pres-sure decay(dp/dtmin),was more marked in control mice than in TFB treated mice.Mortality after MI was greater in control mice than in TFB treated mice.In control mice,capillary density and myocyte width in the nonischemic portion of the LV did not differ before and 28 days after MI, whereas in TFB treated mice, capillary density increased and myocyte width declined after MI. CONCLUSION These results suggest that the presence of TFB limits LV dysfunction and remodeling in a murine model of MI in part by decreasing myocyte hypertrophy in the remote myocardium.

Risk factors associated with the severity of diabetic retinopathy in Qingdao / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM:To investigate and analyse the prevalence and risk factors associated with diabetic retinopathy severity in Qingdao. ·METHODS: This survey consisted of the 2 following parts: 2859 community residents aged >60 years old and 4275 patients with T2DM who were older than 30 years old in Qingdao. Ophthalmic examinations were performed on all patients. A questionnaire was used to obtain the patient's age and gender, the duration of diabetes mellitus(DM), glycaemic control and their knowledge of diabetic retinopathy ( DR ). Blood pressure and haemoglobin levels were recorded. All included patients underwent a comprehensive ophthalmic examination that included a fundus examination and retinal photographs and that assigned a grade for the severity of retinopathy according to the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. Patients with severe non-proliferative or proliferative diabetic retinopathy and clinically significant macular edema ( CSME ) required ophthalmic therapy were assigned to the need-treatment group, while the remaining patients with DR were assigned to the need-observation group. Correlation and regression analyses were performed to determine the required-treatment rate and risk factors for DR. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) after adjustment for age, gender and the duration of diabetes. ·RESULTS: DR was present in 334 (11. 68% ) of the 2859 community residents aged > 60 years old and 1097 (25. 66% ) of the 4275 hospital patients with T2DM, and 48 (14. 81% ) of the residents and 172 ( 15. 68% ) of the hospital patients required ophthalmic therapy. In univariate and multivariate logistic analyses, factors including the age of the patients (51-60 years old: OR, 1. 68; 95% CI, 1. 21-1. 72; 61-70 years old: OR, 1. 55;95% CI, 1. 38-1. 76), the duration of diabetes (11-15 years:OR, 2. 61; 95% CI, 1. 51-4. 72; >15 years: OR, 4. 15; 95% CI, 2. 32-5. 77), glycaemic control (medium: OR, 2. 51;95%CI,1.98-3.92;poor:OR,4.69;95%CI,3.39-6.95), and knowledge of DR ( did not understand: OR, 1. 45;95%CI, 1. 21-1. 95) were significantly associated with the required-treatment rate in DR, while gender, low and advanced age ( 31-50 years old and >70 years old ), duration of disease (<10y), hypertension, and insulin treatment did not. ·CONCLUSION: The prevalence rate and the required-treatment rate in DR in Qingdao are relatively high. Being aged 51-70 years old and having a duration of diabetes>10y, poor glycaemic control and a lack of knowledge of DR were found to be potential risk factors that increased the rate of required ophthalmic therapy in patients with DR. In patients with T2DM who were aged 51-70 years old, we found that focusing on using science and education to strengthen the patients' knowledge of DR, establishing specifications for a community DR screening system, and effectively implementing early intervention in the community of DR - affected individuals were particularly important for preventing and controlling the high DR prevalence and the high rate of DR-associated blindness

Effects of pranoprofen eye drops on corneal endothelium and tears inflammatory factors in perioperative period of cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the effect of pranoprofen eye drops on corneal endothelium and tears inflammatory factors in perioperative period of cataract surgery.METHODS:Totally 60 cases (60 eyes) of senile cataract patients were enrolled in this study.Patients with diabetes or other systemic diseases,with other eye diseases or eye surgery,drug allergy were excluded.All the patients were given ophthalmic surgery for the first time.All the patients were randomly divided into 4 groups,15 patients per group.Each group of patients had been given levofloxacin eye drops preoperatively for 3d,4 times per day,and tobramycin dexamethasone eye drops postoperatively,3 times per day for the first week,2 times per day for the second week.Group A was the control group,without any other drugs.Group B was given pranoprofen eye drops 4 times per day for 3d before the operation.Group C was given pranoprofen eye drops 4 times per day for 1wk after the operation.Group D was given pranoprofen eye drops 4 times per day for 3d before the operation and 1wk after the operation.All the surgeries were done by the same ophthalmologist,using the same phacoemulsification machine and the same ultrasound energy parameters.The loss rate of endothelial cell was measured by corneal endothelium counterometry.Interleukin-6 (IL-6) and tumor necrosis factor (TNF) in the tear fluid were measured by ELISA before surgery (before using eye drops) and 1wk,1mo and 3mo postoperatively.RESULTS:There was no significant difference in patients' gender,age and phacoemulsification time among 4 groups.The levels of inflammatory cytokines IL-6 in the tear fluid of the Group B before surgery had no significant difference compared to that at 3mo postoperatively(P＞ 0.05),but the differences among the other groups at different time points were statistically significant (P＜0.05).There was no significant difference in preoperative among the four groups (P＞0.05).At 1wk after the operation,there was significant difference between the Group A and the other three groups (P＜ 0.05),and there was significant difference between the Group B and the Group D (P＜0.05),but there was no significant difference between the Group B and the Group C,the Group C and the Group D (P＞0.05).At 1mo after the operation,there was significant difference between the Group A and the other three groups (P＜0.05),and there was significant difference between the Group B and the Group C,the Group C and the Group D (P＜0.05),but there was no significant difference between the Group B and the Group D (P＞0.05).At 3mo after the operation,there was significant difference between the Group A and the other three groups (P＜ 0.05),but there was no significant difference between the Group B,the Group C and the Group D (P＞0.05).The levels of inflammatory cytokines TNF in the tear fluid at different time points among each group were significantly different (P＜0.05).There was no significant difference among the four groups in preoperative (P＞ 0.05).At 1w after the operation,there was significant difference between the Group A and the other three groups (P＜0.05),but there was no significant difference between the other three groups respectively (P ＞ 0.05).At 1 mo after the operation,there was significant difference between the Group A and the other three groups (P＜0.05),and there was significant difference between the Group B and the Group C,the Group C and the Group D (P＜0.05),but there was no significant difference between the Group B and the Group D (P＞0.05).At 3mo after the operation,there was significant difference between the Group A and the other three groups (P＜ 0.05),but there was no significant difference between the other three groups respectively (P＞0.05).CONCLUSION:Pranoprofen eye drops have no effect on the loss rate of corneal endothelium.Pranoprofen eye drops could significantly reduced the tears inflammatory factors in perioperative period of cataract surgery.The role to reduce inflammatory cytokines in the postoperative application of pranoprofen eye drops is not obvious compared to other two modes of administration,but the difference is not statistically significant at 3mo.The administration of preoperative and postoperative use of pranoprofen eye drops has no significant advantage in reducing inflammatory cytokines compared with only preoperative use.

Reduction of Tat-interacting Protein 30 Expression Could be a Prognostic Marker in Bladder Urothelial Cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tat-interacting protein 30 (TIP30) has been reported to be a tumor suppressor, with reduced or absent expression in various tumors. However, its role in bladder urothelial cancer (BUC) has not been investigated. Therefore, herein, we investigated the expression of TIP30 protein in BUC and normal bladder mucosa and the clinical significance of TIP30 expression in the prognosis of BUC.</p><p><b>METHODS</b>We reviewed data from 79 cases of BUC and 15 adjacent tissue samples from 79 patients treated at our institution between 2004 and 2007. TIP30 expression was examined by immunohistochemistry. The relationship between TIP30 expression and tumor stage, histological grade, and survival was analyzed. Differences between groups were evaluated using the t-test or matched-pairs test, and differences in the survival rates were analyzed with the log-rank test.</p><p><b>RESULTS</b>TIP30 protein expression was significantly reduced in BUC tissue (t = -6.91, P < 0.05) compared with normal tissue samples, and in invasive bladder cancer (t = 10.89, P < 0.05) compared with superficial bladder cancer. TIP30 protein expression differed significantly among different differentiated groups classified either according to the World Health Organization (2004, F = 17.48, P < 0.01) or World Health Organization (1973, F = 10.68, P < 0.01). TIP30 protein expression was significantly reduced in high-grade papillary urothelial carcinoma compared with papillary urothelial neoplasm of low malignant potential (P < 0.05) and low-grade papillary urothelial carcinoma (P < 0.05). Meanwhile, TIP30 protein expression was significantly reduced in Grade III BUC, compared with Grade I (P < 0.05) and Grade II (P < 0.05). Patients with low TIP30 expression showed a higher incidence of disease progression than those with high TIP30 expression (t = 2.63, P < 0.05). Kaplan-Meier survival analysis showed a strong positive relationship between TIP30 expression and overall survival (OS) (χ2 = 17.29, P < 0.05).</p><p><b>CONCLUSIONS</b>TIP30 expression was associated with clinical tumor stage in BUC, suggesting that it might play an important role in disease progression. Furthermore, TIP30 might predict postoperative OS. Thus, its evaluation might be useful for predicting prognosis.</p>

Management of high-value consumables based on No.1 Military Medical Project / 医疗卫生装备

Objective To solve the problems of hospital high-value consumables during purchase,warehouse-in and-out management,utilization,charging and etc.Methods High-value consumables management was improved based on No.1 Military Medical Project high-value consumables management system and bar code technology.Results Integrated management,whole-course supervision,safe utilization,convenient and accurate charging were realized for high-value consumables.Conclusion Bar code technology contributes to reducing high-value consumables inventory,decreasing hospital cash flow pressure,achieving high value consumables used safely and zero error valuation of financial accounting.It can become an effective management mode of hospital high-value consumables.

Management of high-value consumables based on No.1 Military Medical Project / 医疗卫生装备

Objective To solve the problems of hospital high-value consumables during purchase,warehouse-in and-out management,utilization,charging and etc.Methods High-value consumables management was improved based on No.1 Military Medical Project high-value consumables management system and bar code technology.Results Integrated management,whole-course supervision,safe utilization,convenient and accurate charging were realized for high-value consumables.Conclusion Bar code technology contributes to reducing high-value consumables inventory,decreasing hospital cash flow pressure,achieving high value consumables used safely and zero error valuation of financial accounting.It can become an effective management mode of hospital high-value consumables.

The effects of DEHP on morphology and function of progenitor Leydig cell in rat / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects and mechanisms of diethylhexylphthalate (DEHP) on morphology and function of progenitor Leydig cells (PLC) in rats.</p><p><b>METHODS</b>Twenty pregnant SD rats were randomly divided into 4 groups ( n = 5): normal control group, DEHP low dose group , middle dose group, and high dose group, which were treated from postnatal day (PND) 1 to PND 21 of the pubs with DEHP at the doses of 0, 10, 100, 750 mg/(kg · d) in 0.5 ml of corn oil by gavage respectively. At the end of the treatment, the male pups were killed and blood samples were collected for determination of serum testosterone concentration by chemiluminescence method. The body weight, testis weight and anogenital distance (AGD) were measured. The morphology of PLC was observed by light and transmission electron microscopy. The protein expression of steroidogenic acute regulatory protein(StAR) in PLC was determined by immunohistochemistry. The mRNA expression of insulin-like growth factor-I (IGF-I) in the testis was assayed by real-time PCR.</p><p><b>RESULTS</b>Compared with normal control group, the serum testosterone and AGD of male pubs from the middle and high dose groups were declined significantly (P < 0.01), the testis weight and body weight from high dose group were decreased significantly (P < 0.01), while the testis weight increased in the low dose group (P < 0.05). Under light microscope, PLC showed hyperplasia and cluster aggregation in the low dose group and focal hyperplasia in the middle and high dose group. The spermatogenic cells in seminiferous tubules showed decrease, apoptosis and unfix in the high dose group. Under transmission electron microscope, the PLC showed decreased lipid droplets, smooth endoplasmic reticulum and mitochondriae in the treated group. The mRNA expression of IGF-I increased in the low dose group, and the protein expression of StAR decreased in the middle and high dose group.</p><p><b>CONCLUSION</b>Lactating exposure to DEHP may interfere with the synthesis of testosterone of PLC in male pubs, the decrease of StAR and the damage of PLC may be involved in it.</p>

The effects of paeoniflorin monomer of a Chinese herb on cardiac ion channels / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Because of the potential proarrhythmic effect of current antiarrhythmic drugs, it is still desirable to find safer antiarrhythmic drugs worldwide. Paeoniflorin is one of the Chinese herb monomers that have different effects on many ion channels. The present study aimed to determine the effects of paeoniflorin on cardiac ion channels.</p><p><b>METHODS</b>Whole-cell patch-clamp technique was used to record ion channel currents. L-type calcium current (I(Ca-L)), inward rectifier potassium current (I(K1)), and transient outward potassium current (I(to1)) were studied in rat ventricular myocytes and sodium current (I(Na)), slow delayed rectifier current (I(Ks)), and HERG current (I(Kr)) were investigated in transfected human embryonic kidney 293 cells.</p><p><b>RESULTS</b>One hundred µmol/L paeoniflorin reduced the peak I(Ca-L) by 40.29% at the test potential of +10 mV (from (-9.78 ± 0.52) pA/pF to (-5.84 ± 0.89) pA/pF, n = 5, P = 0.028). The steady-state activation curve was shifted to more positive potential in the presence of the drug. The half activation potentials were (-11.22 ± 0.27) mV vs. (-5.95 ± 0.84) mV (n = 5, P = 0.007), respectively. However, the steady-state inactivation and the time course of recovery from inactivation were not changed. One hundred µmol/L paeoniflorin completely inhibited the peak I(Na) and the effect was reversible. Moreover, paeoniflorin inhibited the I(K1) by 30.13% at the test potential of -100 mV (from -25.26 ± 8.21) pA/pF to (-17.65 ± 6.52) pA/pF, n = 6, P = 0.015) without effects on the reversal potential and the rectification property. By contrast, 100 µmol/L paeoniflorin had no effects on I(to1), I(Ks) or I(Kr) channels.</p><p><b>CONCLUSIONS</b>The study demonstrated that paeoniflorin blocked I(Ca-L), I(Na), and I(K1) without affecting I(to1), I(Ks), or I(Kr). The multi-channel block effect may account for its antiarrhythmic effects with less proarrhythmic potential.</p>

Readthrough of nonsense mutation W822X in the SCN5A gene can effectively restore expression of cardiac Na+ channels W822X / 中华心血管病杂志

<p><b>OBJECTIVE</b>In this study we investigated the functional restoration of nonsense mutations in the SCN5A gene.</p><p><b>METHODS</b>The readthrough-enhancing reagents were introduced to HEK293 cells to suppress one nonsense mutation W822X in the SCN5A gene. Patch-clamp was used to record the whole-cell current and dynamics. Western blot and immunofluorescence staining were used to certify the expression and the location of the sodium channel.</p><p><b>RESULTS</b>In transfected HEK293 cells, the nonsense mutation in SCN5A inhibited the expression level of full-length protein, and the sodium currents from the mutant channels were less than 3% of the wild-type level. Readthrough enhancement by decreasing translation termination efficiency with a siRNA targeting eukaryotic release factor eRF3a (a GTPase that binds eRF1), the sodium current from the mutant cDNAs was restored to as much as 30% of the wild-type. After the treatment by the readthrough-enhancing reagents, the channels from cDNA carrying W822X remained the features of wild-type phenotype, and Western blot and immunochemical staining also showed the expression of full-length channel proteins.</p><p><b>CONCLUSION</b>Readthrough-enhancing reagents could effectively suppress nonsense mutations in SCN5A and partially restore the function of sodium channel and the expression of full-length channels.</p>

The relationship between the expression of NF-kB, TGFbeta1, FN and hepatic fibrosis in diabetic rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the expression of nuclear factor kappa B (NF-kB), transforming growth factor beta1 (TGFbeta1), fibronectin (FN) in liver from diabetic rats.</p><p><b>METHODS</b>Twenty male Sprague-Dawley rats were divided randomly into two groups: normal control group (n = 10) and type 2 diabetic group (n = 10). After 4 weeks of high-fat feeding, diabetic group rats were injected with low dosage streptozotocin (30 mg/kg) intraperitoneally to induce type 2 diabetic rat models. The diabetic rats received high-fat feeding for another 12 weeks. At the end of the experiment, the fibrosis lesion was observed under light microscopy after Masson staining. The mRNA levels of NF-kB, TGFbeta1, FN from rats liver were assayed by semi-quantity RT-PCR, the protein levels of NF-kB, TGFbeta1, FN was detected by IHC.</p><p><b>RESULTS</b>Fibrosis was found in diabetic rats. The levels of TGFbeta1, FN mRNA in liver tissues increased in diabetic rats compared with normal control rats (0.91+/-0.19 vs 0.47+/-0.20, t = 5.233, P less than 0.05; 1.85+/-0.70 vs 1.22+/-0.39, t = 2.463, P less than 0.05). And the protein levels of NF-kB P65, TGFbeta1, FN in liver tissues from diabetic rats were significantly higher than those in normal control rats (10978.77+/-8782.59 vs 4206.86+/-1430.56, Z = 1.979, P less than 0.05; 8551.00+/-4768.68 vs 4036.85+/-1051.12, Z = 2.303, P less than 0.05; 16980.30+/-11529.29 vs 5701.95+/-9461.75, t = -2.391, P less than 0.05).</p><p><b>CONCLUSION</b>Upregulation of NF-kB, TGFbeta1, FN in liver tissues may play a role in the hepatic fibrogenesis in diabetic rats.</p>

Ginkgo biloba extract enhances testosterone synthesis of Leydig cells in type 2 diabetic rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Ginkgo biloba extract (EGB) on the testosterone synthesis in the Leydig cells of type 2 diabetic rats.</p><p><b>METHODS</b>Thirty male SD rats were equally randomised into a normal control, a type 2 diabetic and an EGB group. Morphological changes of Leydig cells were observed by light microscopy (LM) and transmission electron microscopy (TEM), concentrations of serum luteinizing hormone (LH) and testosterone (T) were determined by enzyme linked immunosorbent assay (ELISA), and the mRNA levels in the steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage (P450scc), cytochrome P450 17a-hydroxylase (P450c17), 17beta-hydroxysteroid dehydrogenase 3 (17beta-HSD3) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD1) from the Leydig cells were examined by RT-PCR.</p><p><b>RESULTS</b>Compared with the normal control, there was a significant decrease in the number and volume of Leydig cells, the levels of serum LH and T and the expression of mRNA in StAR, P450scc, 17beta-HSD3 and 3beta-HSD1 in the type 2 diabetes group. And the expression of the P450c17 gene showed a tendency of descending, but with no significance. Compared with the type 2 diabetes group, 12 weeks of EGB treatment caused very slight pathological changes in the Leydig cells, significantly increased the concentrations of blood LH and T, markedly elevated the levels of mRNA in StAR and P450scc and induced an ascending tendency of the expressions of P450c17, 17beta-HSD3 and 3beta-HSD1.</p><p><b>CONCLUSION</b>EGB enhances testosterone synthesis and secretion of Leydig cells by reducing the impairment of the testis in type 2 diabetic rats.</p>

Effect of bushen huayu composite on secretion of lymphocytic interleukin-2 and interleukin-2 receptor expression in the aged / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Bushen Huayu Composite (BSHY) on interleukin-2 (IL-2) secretion and IL-2 receptor expression in the aged.</p><p><b>METHODS</b>IL-2 was examined by methyl thiazolyl tetrazolium (MTT) method and IL-2 dependent cellular stains, IL-2 receptor expression was examined by FACS-indirect immunofluorescence.</p><p><b>RESULTS</b>Aging could result in the decrease in lymphocytic IL-2 secretion and IL-2 receptor expression (P < 0.01, P < 0.05), which could be improved by BSHY (P < 0.01, P < 0.05).</p><p><b>CONCLUSION</b>BSHY has significant up-regulatory effect on immune function of lymphocytes in the aged.</p>