Shengmai San for Treatment of Cardiotoxicity from Anthracyclines: A Systematic Review and Meta-Analysis / 中国结合医学杂志

OBJECTIVE@#To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines.@*METHODS@#Randomized controlled trials (RCTs) were identified by searching China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), PubMed, Cochrane Library, and Embase Databases from the inceptions until December 2020. The Cochrane Handbook was used to evaluate the risk of bias in the included studies. Data analysis was conducted using RevMan 5.3 software.@*RESULTS@#Totally 19 RCTs with 2,331 participants were included in this review. Results showed that in improving arrhythmia (13 RCTs, n=1,877, RR=0.37, 95%CI 0.25 to 0.52, P<0.00001), the treatment group was superior to the control group. In terms of reducing left ventricular end-diastolic diameter (LVEDD, 2 RCTs, n=128, MD=-0.79, 95%CI -0.93 to -0.65, P<0.00001) and left ventricular end systolic diameter (LVESD, 2 RCTs, n=128, MD=-0.58, 95%CI -0.82 to -0.35, P<0.00001), the treatment group was also better than the control group. In reducing myocardial enzymes such as creatine kinase (CK) [(3 RCTs, n=256, SMD=-0.80, 95%CI -1.16 to -0.44, P<0.0001), (2 RCTs, n=126, SMD=-0.62, 95%CI -0.98 to -0.26, P=0.0007)], the treatment group was superior to the control group.@*CONCLUSION@#Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines. However, in the future, it is still necessary to conduct high-quality RCTs to verify its efficacy.

The alterations of apoptosis factor Bcl-2/Bax in the early Parkinson's disease rats and the protective effect of scorpion venom derived activity peptide / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the alterations of apoptosis factor Bcl-2/Bax in the early Parkinson's disease (PD) rats and the protective effect of scorpion venom derived bioactive peptide.</p><p><b>METHODS</b>Healthy male SD rats (180-220 g) were randomly divided into 4 groups (n = 10): early PD model group, sham operation group, scorpion venom derived bioactive peptide control group, scorpion venom derived bioactive peptide therapy group. 6-hydroxydopamine (6-OHDA) was used to prepare the early PD rat model. The immunohistochemistry was used to detect the expression of Bax and Bcl-2 and further explore the mechanism of anti-apoptosis regarding the neuroprotective effect of scorpion venom derived bioactive peptide.</p><p><b>RESULTS</b>The results indicated that compared with the control rats, the immunostaining of Bax in the brain increased significantly while that of Bcl-2 decreased significantly in the lesion side of 6-OHDA treated rats. Interestingly, scorpion venom derived bioactive peptide could attenuate the above abnormal changes.</p><p><b>CONCLUSION</b>Up-regulation of Bax and down-regulation of Bcl-2 could participate in the early stage of PD and the anti-apoptotic mechanism could be involved in the neuroprotective effect exerted by scorpion venom derived activity peptide regarding the dopaminergic neuron in the early stage.</p>

Neuroprotection by scorpion venom heat resistant peptide in 6-hydroxydopamine rat model of early-stage Parkinson's disease / 生理学报

Neuroprotective effect of scorpion venom on Parkinson's disease (PD) has already been reported. The present study was aimed to investigate whether scorpion venom heat resistant peptide (SVHRP) could attenuate ultrastructural abnormalities in mitochondria and oxidative stress in midbrain neurons of early-stage PD model. The early-stage PD model was established by injecting 6-hydroxydopamine (6-OHDA) (20 μg/3 μL normal saline with 0.1% ascorbic acid) into the striatum of Sprague Dawley (SD) rats unilaterally. The rats were intraperitoneally administered with SVHRP (0.05 mg/kg per day) or vehicle (saline) for 1 week. Two weeks after 6-OHDA treatment, the rats received behavior tests for validation of model. Three weeks after 6-OHDA injection, the immunoreactivity of dopaminergic neurons were detected by immunohistochemistry staining, and the ultrastructure of neuronal mitochondria in midbrain was observed by electron microscope. In the meantime, the activities of monoamine oxidase-B (MAO-B), superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the mitochondria of the midbrain neurons, as well as the inhibitory ability of hydroxyl free radical and the antioxidant ability in the serum, were measured by corresponding kits. The results showed that 6-OHDA reduced the optical density of dopaminergic neurons, induced damage of mitochondrial ultrastructure of midbrain neurons, decreased SOD activity, increased MAO-B activity and MDA content, and reduced the antioxidant ability of the serum. SVHRP significantly reversed the previous harmful effects of 6-OHDA in early-stage PD model. These findings indicate that SVHRP may contribute to neuroprotection by preventing biochemical and ultrastructure damage changes which occur during early-stage PD.

The rate of hepatitis B virus resistance to adefovir dipivoxil (ADV) and the evolution of hepatitis B virus in lamivudine-resistant chronic hepatitis B patients with ADV monotherapy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the resistant rate of hepatitis B virus (HBV) to ADV and the dynamic evolution of HBV in lamivudine (Lam)-resistant chronic hepatitis B (CHB) patients.</p><p><b>METHODS</b>Twenty-three Lam-resistant CHB patients were assigned to a 10mg/d ADV monotherapy for 68-116 weeks. The baseline and different time point blood samples after ADV monotherapy were analyzed for ADV-resistant mutations using direct sequencing of PCR products; the evolution of HBV mutations was examined by clonal analysis of serial samples from one patient infected with ADV-associated resistant HBV strains.</p><p><b>RESULTS</b>The cumulative incidence of genotypic ADV resistance at weeks 48 and 96 was 4.3% and 10.5% respectively respectively. The evolution analysis of HBV mutant strains in an ADV-resistant CHB patient showed that the proportion of YMDD mutants gradually decreased with rtA181S mutants increasing over time after ADV monotherapy, and that rtA181S+N236T mutants became the predominant strains during prolonged ADV monotherapy. The addition of Lam to the ongoing ADV treatment had poorer antiviral response in the patient with rtA181S or rtA181S+N236T mutant infection; one clone with multi-drug resistant mutations was selected during Lam and ADV combination therapy.</p><p><b>CONCLUSION</b>Increased risk of adefovir resistance and selection of multi-drug resistant mutations are associated with long-term ADV monotherapy in patients with Lam-resistant chronic hepatitis B.</p>

Inhibitory effects of scorpion venom heat resistant protein on the excitability of acutely isolated rat hippocampal neurons / 生理学报

The effects of scorpion venom heat resistant protein (SVHRP) (National invention patent of China, 2004-10-20, No. ZL01 1 06166.92) on the excitability of acutely isolated rat hippocampal neurons were observed by whole-cell recording and the potential molecular mechanisms underlying its antiepileptic effect were investigated further. The results showed that SVHRP could decrease the excitability of hippocampal neurons. SVHRP (1x 10(-2) microg/mL) altered the action potential (AP) firing mode and decreased the AP firing frequency. Out of 52 neurons observed, 45 (86.54%) generated phasic firing, and 7 (13.46%) generated repetitive firing. Among the 45 neurons generating phasic firing, 8 (17.78%) neurons could still be induced phasic firing after treatment with 1x 10(-2) microg/mL SVHRP and 37 (82.22%) neurons had no responses to the stimulation. The AP firing of neurons was dramatically different after treatment with SVHRP (P<0.01, n=45). Among the 7 repetitive firing neurons, all of them could only generate 1 or 0 AP instead of repetitive firing when SVHRP was applied. The number of APs was 14.57 +/- 1.00 and 0.57 +/- 0.20 before and after SVHRP treatment (P<0.01, n=7). The AP rheobase was (75.10 +/- 8.99) pA and (119.85 +/- 12.73) pA before and after 1x 10(-4) microg/mL SVHRP application, respectively (P<0.01, n=8). The AP threshold was increased from (-41.17 +/- 2.15) mV to (-32.40 +/- 1.48) mV after 1x 10(-4) microg/mL SVHRP treatment (P<0.01, n=8). The peak amplitude of AP was (68.49 +/- 2.33) mV for the neurons before treatment with 1x 10(-4) microg/mL SVHRP and (54.71 +/- 0.81) mV after treatment (P<0.01, n=8). These results showed that SVHRP could decrease the AP firing frequency, increase the AP rheobase and threshold, but decrease the AP peak amplitude of hippocampal neurons. In other words, SVHRP can decrease the excitability of hippocampal neurons. SVHRP probably alters the excitability of hippocampal neurons by affecting sodium channels and this may be one of the underlying molecular mechanisms for its antiepileptic effect.

Inhibition of sodium channels in acutely isolated hippocampal neurons by scorpion venom heat resistant protein / 生理学报

The effects of scorpion venom heat resistant protein (SVHRP) on sodium channel were studied in freshly isolated hippocampal neurons in rat using the whole-cell patch-clamp technique. The results indicated that tetrodotoxin-sensitive voltage-dependent sodium current in hippocampal neurons was inhibited by SVHRP in a dose-dependent manner. The half-inhibition concentration (IC(50)) was (0.0034+/-0.0004) microg/mL, Hill constant (n) was 0.4361+/-0.0318. After SVHRP application, a clear shift of the activation curve of Na(+) channel was shown towards more depolarized potential, resulting in channel opening at more positive membrane potentials. In the presence of 0.1 mug/mL SVHRP, the voltage for half-activation (V(1/2)) and the slope factor of the activation curve were (-23.96+/-0.41) mV and 3.73+/-0.08 (n=8, P<0.05) compared with the control recordings of (-34.38+/-0.62) mV and 4.52+/-0.52 (n=16), respectively. Averaged and normalized curve of steady-state inactivation of Na(+) channel was shifted towards negative potential after treatment of 0.1 and 0.01 mug/mL SVHRP. In the presence of 0.1 mug/mL SVHRP, the voltage for half-inactivation (V(1/2)) and the slope factor determined by a sigmoid fit of the inactivation curve were (-50.69+/-2.55) mV (n=8, P<0.01) and 5.49+/-0.72 (n=8, P<0.05) compared with the control recordings of (-32.60+/-1.52) mV and 6.73+/-0.51 (n=16), respectively. These results suggest that SVHRP blocks the voltage-dependent sodium currents and alters the sodium channel kinetics to decrease the excitability of neurons. This might be an interpretation for the antiepileptic effects of SVHRP.

Application of PCR-RFLP in detection of adefovir dipivoxil resistance-associated mutations in hepatitis B virus / 中国感染与化疗杂志

Objective To establish a convenient,accurate and practical method for detection of adefovir dipivoxil resistance-as- sociated mutation in hepatitis B virus:rtA181V/T/S and rtN236T mutations.Methods According to HBV complete sequences in GenBank,two pairs of primers were designed to amplify the region of HBV reverse transcriptase in order to introduce a BglI restriction site upon PCR product of wild type (wt) and a BseDI restriction site upon PCR product of rt236 mutant type.After amplification,the PCR products were digested with BglI and BseDI separately.We used this method to detect wild,rt181 mu- tant,rt236 mutant plasmids and 3 chronic hepatitis B patients' serum with obvious ADV resistance-associated mutations.We also tested the sensitivity of this method by mixing the wild and mutant plasmids in different proportions.Results The method could detect rt181 and rt236 mutations simultaneously.The result of RFLP analysis was in accordance with that of DNA se- quencing and cloning analysis.This method could detect the mutants even when they comprised only 10% of the total virus population.Conclusions The PCR-RFLP method with high sensitivity can detect rt181 and rt236 mutations simultaneously.It can be used for early detection of ADV resistance-associated mutation in hepatitis B virus.

Effects of scorpion venom heat-resistant protein on kainic acid induced-damage of cultured primitive rat hippocampal neuropeptide Y-nergic neurons / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of scorpion venom heat-resistant protein (SVHRP) on kainic acid induced-damage of cultured primitive rat hippocampal neuropeptide Y-nergic neurons.</p><p><b>METHODS</b>We observed morphological changes, celluar vigor, NPY-immunoreactivity and NPY mRNA expression by means of Thionine staining, MTT assay, immunocytochemistry and RT-PCR, respectively, on the primitively cultured Sprague-Dawley rat hippocampal neuron treated with KA and SVHRP for 24 h.</p><p><b>RESULTS</b>MTT assay and morphologic analysis showed that SVHRP markedly increased neuron survival-rate, and protected them from kA-induced damage. The expression of NPY-immunoreactivity and NPY mRNA in SVHRP group increased obviously compared with other groups.</p><p><b>CONCLUSION</b>SVHRP protected the primitively cultured hippocampal neurons from KA-induced neuroexcitotoxicity and promoted the expression of NPY.</p>

The protective effect of nicotine on dopaminergic neuron of Parkinson's disease mice / 中国应用生理学杂志

<p><b>AIM</b>To investigate the protective effect of nicotine on dopaminergic neurons and its mechanisms in mice with Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).</p><p><b>METHODS</b>C57BL/6J mice were injected with MPTP for 8 days to establish PD model. Nicotine was given for 10 days in the pretreatment group. Animals were examined behaviorally with the pole test and traction test. Tyrosine hydroxylase (TH) and gamma-aminobutyric acid (GABA) were investigated by the immunocytochemistry (ICC) method. The ultrastructural changes of caudate nucleus(CN) were observed by electron microscope.</p><p><b>RESULTS</b>The results showed that pretreatment nicotine could improve the dyskinesia of PD mice markedly. Simultaneously, TH (P < 0.01) neurons and GABA (P < 0.05) neurons were much more in the pretreatment group when compared with those in the model group. The ultrastructural injury of the pretreatment group was also ameliorated.</p><p><b>CONCLUSION</b>Nicotine has a protective effect on the dopaminergic neurons in the MPTP-treated mice.</p>

Effects of chronic administration of PL017 and beta-funaltrexamine hydrochloride on susceptibility of kainic acid-induced seizures in rats / 生理学报

There is evidence that 5-7 d after acute seizure episodes induced by kainic acid (KA) the rats develop a long-lasting increase in the susceptibility to seizures followed by spontaneous recurrent seizures (SRS). The present study was focused on the role of hippocampal mu opioid receptors (MORs) in the susceptibility of rats to seizures with the KA model of epilepsy. The rats received a convulsant dose of KA (10 mg/kg, i.p.) were continuously infused with a selective MOR agonist PL017 (2.09, 2.59, 3.29 microg/microl), or a selective MOR antagonist beta-funaltrexamine hydrochloride (beta-FNA, 0.88, 1.10, and 1.35 microg/microl) into ventral hippocampus by means of mini-osmotic pumps. Seven days later, the susceptibility of rats to seizures was checked by a subconvulsant dose of KA (5 mg/kg, i.p.). PL017 infusion shortened the latency and increased the stage of seizures induced by subconvulsant dose of KA in a dose-dependent manner. In contrast, infusion of beta-FNA exhibited a dose-dependent effect against seizures challenged by subconvulsant dose of KA. These results indicate that hippocampal MOR may exert a promoting effect on the susceptibility of rats to KA-induced seizures.

Inducible nitric oxide synthase induces beta-amyloid neurotoxicity in vivo / 中国应用生理学杂志

<p><b>AIM</b>To investigate the causative role of nitric oxide synthase (NOS) and nitric oxide (NO) in neurotoxicity of beta-amyloid (Abeta) and the pathogenesis of Alzheimer's disease (AD).</p><p><b>METHODS</b>Using behavioral and neuropathological methods, we observed the effects of Abeta(1-40) injection into hippocampi on rats learning and memory in Y maze and on the neuropathology in hippocampi. The intervention by intraperitoneal administration of aminoguanidine (AG), a selective inducible NOS (iNOS) inhibitor, and 7-nitroindazole (7-NI), a selective neuronal NOS (nNOS) inhibitor, in the neurotoxicity of Abeta(1-40) was studied then.</p><p><b>RESULTS</b>The capability of acquisition and retrieval in Y maze and local neurons in hippocampus of the rats were impaired significantly after Abeta(1-40) injection. Intraperitoneal administration of AG, but not 7-NI, could prevent the damages caused by Abeta(1-40) injection above-mentioned.</p><p><b>CONCLUSION</b>iNOS/NO participates in the mechanisms of Abeta-induced neurotoxicity and may play an important role in the pathogenesis of AD.</p>

The effect of cyclooxygenase-2 on dopaminergic neurons in substantia nigra of Parkinson's disease mice induced by MPTP / 中国应用生理学杂志

<p><b>AIM AND METHODS</b>Using Strain C57/BL of COX-2 deficient mice, the effect of Cyclooxygenase-2 (COX-2) on dopaminergic neurons in substantia nigra of Parkinson's disease (PD) mice induced by intraperitoneal injections of MPTP-HCl were investigated by immunocytochemistry(ICC) .</p><p><b>RESULTS</b>We found that the mortality in COX-2 heterozygous mice is much lower than that in wild type mice (P < 0.01) after injection of MPTP (30 mg/kg/day). The result of semiquantitative immunocytochemical staining showed that the number of tyrosine hydroxylase (TH) immunoreactive neurons in the substantia nigra pars compacta (SNc) declined more significantly in MPTP-treated wild type mice than that in COX-2 heterozygotes mice (P < 0.01).</p><p><b>CONCLUSION</b>COX-2 may be related with lesion of dopaminergic neurons in the SNc of PD.</p>

Neuropathologic investigation of area tempestas sclerosis in epileptic sensitive rats / 中国应用生理学杂志

<p><b>AIM AND METHODS</b>The relation between AT sclerosis (loss of neurons and proliferation of astrocytes) and long-lasting epileptic susceptibility was investigated by thionine staining, GFAP immunohistochemistry and observing the behavior of rats, after scorpion venom (SV) or normal saline (NS) administrated for three week.</p><p><b>RESULTS</b>Compared with NS+ NS group, both the loss of neurons and proliferation of astrocytes were very marked in KA+ NS group (epileptic susceptible rats) (P < 0.05), but those changes were not visible in KA+ NS group (epileptic nonsusceptible rats).</p><p><b>CONCLUSIONS</b>It suggested that AT sclerosis may be one of important reasons of the long-lasting epileptic susceptibility.</p>