Regulation of intestinal micro ecology between raw and salt-processed Alpinia oxyphylla on renal injury rats.

Alpinia oxyphylla Fructus is one of the traditional Chinese medicine plants in the treatment of kidney injury. In clinical practice, crude Alpinia oxyphylla Fructus (CAOF) and salt-processed Alpinia oxyphylla Fructus (SAOF) are the two commonly used drugs specificated in the prevention and treatment of diabetic nephropathy (DN). However, the intestinal micro ecology regulation between CAOF and SAOF on DN has not been reported. In this paper, intestinal micro ecology regulation activities between CAOF and SAOF in DN rats were compared and analyzed by short-chain fatty acids (SCFAs) and intestinal flora analysis. The results showed that both SAOF and CAOF can regulate the intestinal flora metabolite SCFAs level in DN rats, reduce blood glucose concentration and improve inflammatory reaction. The intestinal flora analysis showed SAOF and CAOF could increase the intestinal bacterial diversity. The treatment of renal injury may be related to their increased intestinal bacterial diversity.

Efficacy of preoperative intravitreal injection of Conbercept combined with 25G+ pars plana vitrectomy in the treatment of proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the efficacy of preoperative intravitreal injection of conbercept combined with 25G+ pars plana vitrectomy(PPV)in the treatment of proliferative diabetic retinopathy(PDR).METHODS: The clinical data of 154 patients(176 eyes)with PDR admitted to our hospital from January 2019 to June 2021 were collected for retrospective analysis. According to the treatment methods, 80 patients(92 eyes)in combined treatment group were treated with preoperative intravitreal injection of conbercept combined with 25G+PPV, and 74 patients(84 eyes)in control group were given 25G+PPV only. The postoperative clinical efficacy and levels of adipokines [adiponectin(APN), retinol binding protein 4(RBP4)] before and after surgery were compared between both groups of patients.RESULTS: The combined treatment group showed better clinical efficacy than the control group at 1mo after surgery(P<0.05). Both groups had lower RBP4 levels at 3mo after surgery(P<0.05), with the combined treatment group showing a lower level than the control group(P<0.05). Serum APN levels significantly increased in both groups after surgery(P<0.05), with the combined treatment group having a higher level than the control group(P<0.05). The combined treatment group had lower incidence rates of retinal proliferation and postoperative complications after than the control group 3mo of follow-up(P<0.05).CONCLUSION: Preoperative intravitreal injection of conbercept combined with 25G+PPV is beneficial in improving the therapeutic effect of PDR and reducing the incidence rates of complications, which may be related to the regulations of the expressions of adipokines.

Correlation analysis of vision and changes of macular structure and microcirculation in myopic maculopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the changes of macular morphology and microcirculation in myopic maculopathy(MM), and investigate theirs correlation and effects on vision.METHODS: Case-control study. A total of 165 patients(189 eyes)with high myopia and 154 healthy volunteers(154 eyes)from October 2016 to December 2018 were selected. According to the classification of Meta-analysis for pathologic myopia(META-PM), participants were divided into M0 group(category 0, 41 eyes), M1 group(category 1, 53 eyes), M2 group(category 2 and 3, 52 eyes), and myopic choroidal neovascularization(mCNV)group(43 eyes). All participants underwent optical coherence tomography angiography(OCTA)examination. Morphological and microcirculation parameters of retina at different layers were compared between groups. Pearson correlation was used to assess the correlation between morphological and microcirculation parameters. Correlations between vision and other parameters were analyzed using multiple linear regression analysis.RESULTS:Foveal full retinal thickness(FRT)and outer retinal thickness(ORT)were all lower in M0, M1 and M2 groups than those of control group(all P<0.01). Foveal superficial capillary plexus vessel density(SVD)and deep capillary plexus vessel density(DVD)were all lower in M2 and mCNV groups than those of the control group(all P<0.01). Parafoveal FRT and ORT were all lower in M0, M1, M2 and mCNV groups than those of the control group(all P<0.01). Parafoveal inner retinal thickness(IRT), SVD and DVD were all lower in M2 and mCNV groups than those of the control group(all P<0.01). Subfoveal choroidal thickness(SFCT)and choroid capillaries vessel density(CVD)were all lower in M0, M1, M2 and mCNV groups than those of the control group(all P<0.01). Foveal vessel density of retina and choroid were positively correlated with its thickness in patients with MM without CNV(all P<0.05). Multivariate analysis showed that axial length(AL), diffuse or patchy chorioretinal atrophy were influencing foctors of best corrected visual acuity(BCVA; all P<0.01).CONCLUSION:Retinal morphological changes precede microcirculation changes in MM. Most of all, ORT changes precede IRT changes. Foveal vessel density of retina and choroid were positively correlated with its thickness. The main influencing factors of BCVA were AL and types of MM.

Adrenomedullin induces heme oxygenase-1 gene expression and cGMP formation in rat vascular smooth muscle cells.

Adrenomedullin (ADM) is a potent vasodilatory peptide. It regulates blood pressure by increasing cyclic adenosine monophosphate (cAMP) and guanosine-3',5'-monophosphate (cGMP). We sought to investigate the effect of ADM on heme oxygenase-1 (HO-1) gene expression and cGMP formation in cultured rat vascular smooth muscle cells (VSMCs). ADM treatment, 10(-9) and 10(-8) mol/L, increased cGMP production, and it increased the intracellular cGMP content of platelets coincubated with VSMCs. It increased cGMP content by 158.8% and 273.5%, respectively; increased HO-1 activity by 49.5% and 87%, respectively; augmented HO-1 protein levels by 66% and 126%, respectively; upregulated the steady-state level of HO-1 mRNA by 73% and 159%, respectively, and increased HO-1 mRNA transcription synthesis by four- and seven-fold, respectively. These results suggest that ADM induces HO-1 gene expression and cGMP formation in rat VSMCs.

Altered phospholamban-calcium ATPase interaction in cardiac sarcoplasmic reticulum during the progression of sepsis.

The purpose of this study was to investigate alterations of phospholamban phosphorylation and its interaction with Ca2+ transport(Ca2+-ATPase activity and Ca2+ uptake) in sarcoplasmic reticulum (SR) during the progression of sepsis. Sepsis was induced by cecal ligation and puncture (CLP). Phospholamban phosphorylation was studied by the labeling of the myocardial ATP pool by perfusing isolated rat hearts with [32P]H3PO4 followed by identification of the phosphorylated phospholamban. Results show that phospholamban phosphorylation was increased by 153% during the early hyperdynamic phase (9 h after CLP), while it was decreased by 51% during the late hypodynamic phase (18 h after CLP) of sepsis. The increase in phospholamban phosphorylation during early sepsis was associated with increases in +dP/dt(max) and tissue cAMP content, while Ca2+ transport, left ventricular developed pressure (LVDP), and -dP/dt(max) remained unchanged. The decrease in phospholamban phosphorylation during late sepsis was accompanied by decreases in Ca2+ transport, LVDP, +/-dP/dt(max), and tissue cAMP content. When isoproterenol was present in the perfusion medium, all parameters measured were stimulated in all three experimental groups (control, early sepsis, and late sepsis) except that Ca2+-ATPase activity and SR Ca2+ uptake were unresponsive in the early and the late septic groups. These findings demonstrate that during the late hypodynamic phase of sepsis, the observed decrease in myocardial contractility was due to the decrease in phospholamban phosphorylation, which resulted in decreased Ca2+ transport across the SR. In contrast, during the early hyperdynamic phase of sepsis, the increase in phospholamban phosphorylation did not correlate with increases in Ca2+ uptake and Ca2+-ATPase activity. Thus, the interaction between phospholamban phosphorylation and Ca2+ transport across the SR was disrupted during the early phase of sepsis.

Transcriptional regulation of cardiac sarcoplasmic reticulum calcium-ATPase gene during the progression of sepsis.

Changes in sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) gene expression in the rat heart during different phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). Septic rats were divided into two groups: the early hyperdynamic (9 h after CLP, early sepsis) and the late hypodynamic (18 h after CLP; late sepsis) groups. Western blot analyses reveal that SERCA2a protein level remained unaltered during early sepsis but was decreased by 59% during late sepsis. Northern blot analyses show that the steady-state level of SERCA2a mRNA stayed unchanged during the early phase but was decreased by 43% during the late phase of sepsis. Nuclear runoff assays show that the transcription rate of SERCA2a gene transcript remained unaffected during early sepsis but was decreased by 34% during late sepsis. The actinomycin D pulse-chase studies indicate that the half-life of SERCA2a mRNA was unaffected during the early and the late phases of sepsis. These findings demonstrate that during the early phase of sepsis, the protein level, the mRNA abundance, and the transcription rate of SERCA2a remained unaltered, whereas during the late phase of sepsis, the rate of transcription of SERCA2a was decreased, and the decreased transcription rate was associated with decreases in SERCA2a mRNA abundance and SERCA2a protein level in the rat heart. Based on these data, it is concluded that SERCA2a gene expression decreased during the late phase of sepsis in the rat heart and that the decreased expression was regulated at the transcriptional level.

G protein and adenylate cyclase complex-mediated signal transduction in the rat heart during sepsis.

Changes in the protein level of various subunits of GTP-binding protein and the activity of adenylate cyclase in the rat heart during different phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into three groups: control, early sepsis, and late sepsis. Early and late sepsis refers to those animals sacrificed at 9 and 18 h, respectively, after CLP. The protein levels of various subunits of GTP-binding protein were determined by Western blot analysis. The activity of adenylate cyclase was measured based on the rate of formation of cAMP from [alpha-32P]ATP. The results show that protein levels of G alphas and G beta remained stable during the early and the late phases of sepsis. The protein levels of G alpha i-2 and G alpha i-3 remained relatively unaltered during the early phase of sepsis, but they were increased by 46.5% (P < 0.05) and 61.3% (P < 0.01), respectively, during the late phase of sepsis. The basal adenylate cyclase activity remained unchanged during the early phase while it was decreased by 25.7% (P < 0.05) during the late phase of sepsis. The isoproterenol-stimulated adenylate cyclase activity was unchanged during early sepsis while it was decreased by 44.6% (P < 0.01) during late sepsis. These data demonstrate that during the late hypodynamic phase of sepsis, myocardial G alpha i-2 and G alpha i-3 protein levels were increased and the increases were coupled with a reduction in adenylate cyclase activity. Because GTP-binding proteins mediate sympathetic control of cardiac function, the present findings may have a pathophysiological significance in contributing to the understanding of the pathogenesis of cardiac dysfunction during the late stage of sepsis.

Group II Phospholipase A(2) Activity and Its Molecular Regulation in Rat Heart during Sepsis.

Changes of activity and content of myocardial group II phospholipase A(2) and its mRNA transcription and stability during rat sepsis were investigated. Results showed that, compared with control group,myocardial group II phospholipase A(2) activity in early and late sepsis decreased by 25.0%(P<0.05) and increased by 47.6%(P<0.01),respectively group II phospholipase A(2) protein concentration reduced by 27.0% and augmented by 48.0%(P<0.01),respectively. Myocardial group II phospholipase A(2) mRNA transcription rate and content showed similar two-phases changes. The mRNA transcription rate during early and late sepsis decreased by 45.0% and increased by 70.0%(P<0.01),respectively. The mRNA content decreased by 34.1% in early sepsis and increased by 157.0% in late sepsis(P<0.01), respectively. The half-life of group II phospholipase A(2) mRNA remained unchanged notably during early and late stage of sepsis. These data suggest that myocardial group II phospholipase A(2) activity decreased in early stage of sepsis and increased in its late stage, and these changes were regulated transcriptionally.

[Comparison of ryanodine binding to cardiac sarcoplasmic reticulum and nuclear envelope of rat].

AIM: The characteristics of ryanodine receptor in rat cardiac sarcoplasmic reticulum (SR) and nuclear envelope (NE) were studied. METHODS: Velocity and isopyknic gradient centrifugation was employed to fractionate rat SR and NE. Ryanodine receptor was assayed with [3H] ryanodine saturate binding to the preparations. RESULTS: The maximal binding (Bmax) and dissociating constant (Kd) of ryanodine receptor in rat cardiac NE were, 1.7% and 60% of those in SR respectively. Phosphorylation in vitro by PKA and PKC increased Bmax of the receptors in SR by 372% and 121%, and augmented those in NE by 221% and 306%, without any effects on Kd. CONCLUSION: Ryanodine receptors were present in rat myocardial NE, with lower density and higher affinity than those located in SR, which can be activated by PKA and PKC.

Expression of nuclear export factor CRM1 and p27 in glioma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression of nuclear export factor CRM1, Ser10-phosphorylated p27 and p27 in human gliomas.</p><p><b>METHODS</b>The expression of CRM1, Ser10-phosphorylated p27 and p27 were investigated in 70 cases of human gliomas and 10 specimens of the normal brain tissue by immunohistochemical technique and Western blot.</p><p><b>RESULTS</b>There were significant differences on the expression levels of CRM1, Ser10-phosphorylated p27 and p27 among normal brain tissue, gliomas of grades II and gliomas of grades III plus IV (P < 0.01). The expression of CRM1 in gliomas was inversely correlated with the expression of p27 (r(s) = -0.727, P < 0.01) and positively correlated with the expression of Ser10-phosphorylated p27 (r(s) = 0.954, P < 0.01) and Ki-67 (r(s) = 0.799, P < 0.01). Moreover, the expression of Ser10-phosphorylated p27 was inversely correlated with p27 (r(s) = -0.744, P < 0.01) and positively correlated with Ki-67 (r(s) = 0.785, P < 0.01).</p><p><b>CONCLUSIONS</b>CRM1, through recognizing and binding with Ser10-phosphorylated p27, may promote moving of p27CRM1 from its original locating sites; act as a critical signaling component in the proliferative process of glioma cells and then, plays an important role in the development of gliomas.</p>

A randomized phase II trial of docetaxel and doxorubicin in treatment for patients with non-small-cell lung cancer who have failed previous platinum-based chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to evaluate the efficacy, toxicity and safety of doxorubicin combined with domestically produced docetaxel versus with taxotere, and to investigate whether these two regimens result in similar outcomes in the treatment for non-small-cell lung cancer (NSCLC) patients who failed previous platinum-based chemotherapy.</p><p><b>METHODS</b>Eighty-eight NSCLC patients were enrolled into this clinical phase II trial. The patients randomly received either domestic docetaxel (study arm) or taxotere (control arm) at a dose of 70 mg/m2 on D2, while doxorubicin at a dose of 40 mg/m2 on D1 was administered in both groups. It was repeated every 3 weeks, totally for three cycles. No granulocyte colony-stimulating factor was used to prevent granulocytopenia. The response rate and toxicity were evaluated using World Health Organization toxicity scale and Karnofsky performance status scale.</p><p><b>RESULTS</b>Of the 88 patients, 81 were evaluable in terms of efficacy. There was no complete responder in this series. The response rate (RR) was 17.1% in the study arm versus 7.5% in the control arm, and the clinical benefit rate (CBR) was 80.5% in the study group versus 72.5% in the control group. The most frequent grade 3 or 4 toxicities were neutropenia, leucopenia and gastrointestinal symptoms. Other toxicities such as alopecia and vomiting were mild and generally well tolerated. No fluid retention was noticed.</p><p><b>CONCLUSION</b>The administration of doxorubicin 40 mg/m2 on D1 combined with domestic docetaxel 70 mg/m2 on D2 is proved to be as effective and tolerable as with taxotere. The domestic drug docetaxel may be considered as an alternative for patients with non-small-cell lung cancer who failed previous platinum-based chemotherapy.</p>

Docetaxel in the treatment of advanced breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy, toxicity and safety of an new domestic docetaxel in the treatment of pretreated advanced breast cancer.</p><p><b>METHODS</b>Fourty-four breast cancer patients who had failed in first-line chemotherapy were included in this trial. They received docetaxel as the second-line chemotherapy. Docetaxel was administered alone at a dose of 70 mg/m2 every 3 weeks. The use of granulocyte colony-stimulating factor to prevent granulocytopenia was not permitted. The response rate and toxicity were evaluated by World Health Organization toxicity scale and performance status by Karnofsky scale.</p><p><b>RESULTS</b>Of the 41 evaluable patients, 4 achieved complete response and 14 partial remission, with a response rate and clinical benefit rate of 43.9% and 85.4%, respectively. Grade 3 or grade 4 neutropenia developed in 42.9%, alopecia in 7.1% and vomiting in 4.8% of these patients. Fluid retention was not observed in this series.</p><p><b>CONCLUSION</b>Three-week administration of docetaxel alone at a dose of 70 mg/m2 is effective and tolerable. It provides an alternative for the pretreated advanced breast cancer patients.</p>

Adaptation of myofibrilla, MHC and metabolic enzyme of rabbit diaphragm muscle to different frequency chronic electrical stimulation / 中国应用生理学杂志

<p><b>AIM</b>To detect effect of the different frequency of chronic electrical stimulation (CES) on myofibrillar isoform, myosin heavy chain (MHC) and metabolic enzyme activities.</p><p><b>METHODS</b>The histochemical method and SDS-polyacrylamide gel electrophoresis were respectively employed.</p><p><b>RESULTS</b>(1)There were a significant increase in I myo-fibrillar isoform and I MHC isoform and decrease in II B myofibrillar isoform and II B MHC isoforms in the chronic low frequency electrical stimulation (CLFES) 10 Hz and 20 Hz groups, but opposite results were found in the chronic high frequency electrical stimulation (CHFES) 50 Hz and 100 Hz groups. (2) There were a significant increase in the aerobic-oxidative enzyme activities and capacity, and a concomitant significant drop in glycolysis enzyme activities in CLFES groups, but opposite results were found in CHFES 50 Hz and 100 Hz groups.</p><p><b>CONCLUSION</b>It was suggested that there was a significant dependent relation between chronic electrical stimulation frequency and myofibrilla isoforms, myosin heavy chain (MHC) and metabolic enzyme activities.</p>

Effect of chronic electrical stimulation of phrenic nerve at different frequencies on mRNA and protein expression of skeletal DHPR(alpha1) and RyRs in the diaphragm muscle of rabbits / 生理学报

The mRNA and protein expression of skeletal dihydropyridine receptor isoform alpha1 subunit (DHPR(alpha1)) and ryanodine receptor(1-3) (RyR(1-3)) during chronic electrical stimulation (CES) of phrenic nerve have rarely been explored. In the present study, we explored the signal translation mode of calcium release unit in diaphragm muscle of rabbits after CES. Thirty rabbits were used and randomly divided into the normal, 10, 20, 50 and 100 Hz groups. Phrenic nerve was continuously (5 weeks, 2x 2 h/d) stimulated at 10, 20, 50 and 100 Hz respectively (impulse width 0.2 ms, 3~6 waves/time, 45 times/min, 10~20 V). Reverse transcription PCR and immunohistochemical methods were employed. The results showed that mRNA and protein expressions of DHPR(alpha1) and RyR(1) in 10 and 20 Hz groups were more significantly lower than those in the control group (P<0.01), but mRNA and protein expressions of DHPR(alpha1) and RyR(1) were significantly higher in 50 and 100 Hz groups than those in the control group (P<0.01); a lower level of mRNA expression of RyR(2) was found in 10 and 20 Hz groups. It is suggested that the calcium release unit and the signal transduction mode between DHPR and RyRs were altered from conformational changes of linked proteins to Ca(2+)-induced Ca(2+) release (CICR) in the diaphragmatic muscle of rabbits after chronic low-frequency electrical stimulation of phrenic nerve for 5 weeks.