Contrast-enhanced CT-based radiomics differentiate anterior mediastinum lymphoma from thymoma without myasthenia gravis and calcification.

AIM: To explore the value of a radiomics model based on enhanced computed tomography (CT) in differentiating anterior mediastinal lymphoma (AML) and thymoma without myasthenia gravis (MG) and calcification. MATERIALS AND METHODS: The present study analysed patients who were diagnosed histologically with AML and thymoma in three independent institutions. All pre-treatment patients underwent enhanced CT. In the training group of patients from institutions 1 (the First Affiliated Hospital of Kunming Medical University) and 3 (the Yunnan Cancer Hospital), two radiologists independently analysed the enhanced CT images and performed manual segmentation of each tumour. Radiomics features were screened using interobserver interclass coefficient (ICC) analysis, feature correlation analysis, and L1 regularisation. The discriminative efficacy of the logistic regression model was evaluated using receiver operating characteristic (ROC) analysis. Validation group of patients from institution 2 (the Second Affiliated Hospital of Zhejiang University School of Medicine) was used to validate the proposed models. RESULTS: A total of 114 patients were enrolled in this study and 1,743 radiomics features were extracted from the enhanced CT images. After feature screening, the remaining 37 robust radiomics features were used to construct the model. In the training group, the AUC of the model was 0.987 (95% confidence interval [CI]: 0.976-0.999), the sensitivity, specificity, and accuracy were 0.912, 0.946, and 0.924, respectively. In the validation group, the AUC of the model was 0.798 (95% CI: 0.683-0.913), the sensitivity, specificity, and accuracy were 0.760, 0.700, and 0.743, respectively. CONCLUSION: The radiomics model created provided effective information to assist in the selection of clinical strategies, thus reducing unnecessary procedures in patients with AML and guiding direct surgery in patients with thymoma to avoid biopsy.

FLASHForward: plasma wakefield accelerator science for high-average-power applications.

The FLASHForward experimental facility is a high-performance test-bed for precision plasma wakefield research, aiming to accelerate high-quality electron beams to GeV-levels in a few centimetres of ionized gas. The plasma is created by ionizing gas in a gas cell either by a high-voltage discharge or a high-intensity laser pulse. The electrons to be accelerated will either be injected internally from the plasma background or externally from the FLASH superconducting RF front end. In both cases, the wakefield will be driven by electron beams provided by the FLASH gun and linac modules operating with a 10 Hz macro-pulse structure, generating 1.25 GeV, 1 nC electron bunches at up to 3 MHz micro-pulse repetition rates. At full capacity, this FLASH bunch-train structure corresponds to 30 kW of average power, orders of magnitude higher than drivers available to other state-of-the-art LWFA and PWFA experiments. This high-power functionality means FLASHForward is the only plasma wakefield facility in the world with the immediate capability to develop, explore and benchmark high-average-power plasma wakefield research essential for next-generation facilities. The operational parameters and technical highlights of the experiment are discussed, as well as the scientific goals and high-average-power outlook. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

[Relationship of distribution frequency of HLA antigen/antibody and PIRCHE score with DSA production and AMR occurrence].

Objective: To analyze the distribution frequency of HLA antigen gene and antibody, and explore the relationship of PIRCHE score with DSA production and AMR occurrence. Methods: Kidney transplantation cases of department Kidney transplantation, the First Hospital of Xi'an Jiaotong University from November 2013 to June 2017 were included in our study. HLA high resolution typing were detected with LAB Type (TM) SSO method. HLA classⅠ & Ⅱ antibody detection were tested by LAB screen Single Antigen beads with Luminex 200 technology. PIRCHE score were graded with PIRCHE score system. Results: HLA high resolution classification data of 798 recipients and 409 donors showed that HLA A2, A11, A24 were common in HLA A locus; HLA B46, B51 B60, B35, B62, B61 were common in HLA B locus; HLA DR9, DR4, DR15, DR12, DR7, DR11 were common in HLA DR locus; HLA DQ7, DQ6, DQ5, DQ9, DQ2 were common in HLA DQ locus. The positive cases of HLA class Ⅰ & Ⅱ antibody and DSA were 105, 40 and 32, respectively. The most common of HLA class Ⅰ antibody were A24 and B7 antibody; the most common of HLA class Ⅱ antibody was DQ antibody, including DQ2, DQ9, DQ4, DQ6, DQ7 and DQ8. PIRCHE scores of living donor transplantation recipients were significantly lower than DCD group (P<0.01). PIRCHE score of DSA(+) and DSA(+)AMR(+) group were markedly higher than that of DSA(-)and DSA(+)AMR(-)group, respectively(P<0.05); analysis of ROC curve on PIRCHE scores could predict DSA production and AMR occurrence. The AUC for prediction DSA production was 0.80, and the critical value was 115.5. For prediction of AMR, the AUC was 0.89 and the critical value was 133.5. Conclusions: The common HLA antigens have stronger immunogenicity, and easy to stimulate the body to produce HLA antibodies; matching of common antigen sites and HLA class Ⅱ antigen should be attached importance before kidney transplantation. PIRCHE score can predict the generation of DSA and the occurrence of AMR effectively. PIRCHE score for HLA match, is more sensitive than traditional methods, and contains more information.

Comparison of the clinical and CT features between COVID-19 and H1N1 influenza pneumonia patients in Zhejiang, China.

OBJECTIVE: To explore the different clinical and CT features distinguishing COVID-19 from H1N1 influenza pneumonia. PATIENTS AND METHODS: We compared two independent cohorts of COVID-19 pneumonia (n=405) and H1N1 influenza pneumonia (n=78), retrospectively. All patients were confirmed by RT-PCR. Four hundred and five cases of COVID-19 pneumonia were confirmed in nine hospitals of Zhejiang province, China from January 21 to February 20, 2020. Seventy-eight cases of H1N1 influenza pneumonia were confirmed in our hospital from January 1, 2017 to February 29, 2020. Their clinical manifestations, laboratory test results, and CT imaging characteristics were compared. RESULTS: COVID-19 pneumonia patients showed less proportions of underlying diseases, fever and respiratory symptoms than those of H1N1 pneumonia patients (p<0.01). White blood cell count, neutrophilic granulocyte percentage, C-reactive protein, procalcitonin, D-Dimer, and lactate dehydrogenase in H1N1 pneumonia patients were higher than those of COVID-19 pneumonia patients (p<0.05). H1N1 pneumonia was often symmetrically located in the dorsal part of inferior lung lobes, while COVID-19 pneumonia was unusually showed as a peripheral but non-specific lobe distribution. Ground glass opacity was more common in COVID-19 pneumonia and consolidation lesions were more common in H1N1 pneumonia (p<0.01). COVID-19 pneumonia lesions showed a relatively clear margin compared with H1N1 pneumonia. Crazy-paving pattern, thickening vessels, reversed halo sign and early fibrotic lesions were more common in COVID-19 pneumonia than H1N1 pneumonia (p<0.05). Pleural effusion in COVID-19 pneumonia was significantly less common than H1N1 pneumonia (p<0.01). CONCLUSIONS: Compared with H1N1 pneumonia in Zhejiang, China, the clinical manifestations of COVID-19 pneumonia were more concealed with less underlying diseases and slighter respiratory symptoms. The more common CT manifestations of COVID-19 pneumonia included ground-glass opacity with a relatively clear margin, crazy-paving pattern, thickening vessels, reversed halo sign, and early fibrotic lesions, while the less common CT manifestations of COVID-19 pneumonia included consolidation and pleural effusion.

[Endoscopic lateral neck dissection via the breast and transoral approaches for papillary thyroid carcinoma: a report of 10 cases].

Objective: To investigate the feasibility of endoscopic lateral neck dissection via the breast and transoral approaches (ELNDBTOA) for papillary thyroid carcinoma (PTC). Methods: From February 2015 to April 2019, 10 patients with PTC (cN1b) including 1 male and 9 females aged from 22 to 53 years old received ELNDBTOA in the General Surgery Department of Zhongshan Hospital, Xiamen University. Total thyroidectomy, the central lymph node dissection and the selective neck dissection (levels Ⅱ, Ⅲ and Ⅳ) were performed endoscopically via the breast approach, and then the residual lymph nodes were dissected via transoral approach. The medical records, operation time, blood loss, complications and postoperative follow-up outcomes were analyzed retrospectively. SPSS 22.0 software package was used for statistical processing of clinical data of patients. Results: All cases were successfully treated with ELNDBTOA without transfer to open surgery. The average operative time was (362.5±79.7) min, the blood loss was (23.0±14.9) ml, and the postoperative hospital stay was (5.1±1.3) days. The mean number of harvested cervical lymph nodes were (34.2±25.8), and the mean number of positive lymph nodes were (6.5±4.9). Lymph nodes were dissected by the further dissection via oral approach in 6 patients and a total of 9 lateral lymph nodes were havested from 2 of the 6 patients, with 3 positive lymph nodes. Two patients had transient skin numbness in the mandibular area and recovered within two weeks. One patient developed transient hypoparathyroidism and recovered within two months. No secondary bleeding, recurrent laryngeal nerve paralysis, chylous leakage, neck infection, permanent hypoparathyroidism or other complications were observed. The follow-up time was from 16 to 66 months with a median of 42.5 months, no tumor recurrence or metastasis occurred, and also no obvious deformity, abnormal sensation or movement in the chest, neck and mouth was observed. Conclusions: ELNBTOA is safe and feasible, with good cosmetic outcome.

[Clinical experience in transoral endoscopic thyroidectomy via sublingual and vestibular approach: a report of 98 cases].

Objective: To summarize the clinical experience in transoral endoscopic thyroidectomy via sublingual and vestibular approach (TOETSLVA). Methods: We retrospectively reviewed the medical record of patients who underwent TOETSLVA in our department from November 2011 to May 2020, including 3 males and 95 females, aged from 18 to 57 years old. Initial 81 cases were categorized in "Period A (November 2011-November 2015)" and subsequent 17 cases in "Period B (August 2019-May 2020)" . Data about demographics, operation time and complications were collected. SPSS 22.0 software was used for statistical analysis. Results: In Period A, the average age of patients was (34.2±9.4) years old; the mean tumor diameter was (2.33±0.80) cm; postoperative pathology showed benign nodules in 76 cases and malignant carcinoma in 5 cases; there were 65 cases of unilateral subtotal thyroid lobectomy, 6 cases of isthmus lobectomy, and 5 cases of bilateral subtotal thyroid lobectomy, with the mean operation time of (132.70±47.22) min; in 5 cases of unilateral thyroid lobectomy with central lymph node dissection, the mean operation time was (185.4±31.40) min; postoperative neck infections occurred in 6 cases; temporary vocal cord paralysis occurred in 1 case, which it recovered within two months; and CO(2) gas embolism occurred in 2 cases. In Period B, the average age of patients was (35.1±8.5) years old; mean tumor diameter was (1.32±0.67) cm; postoperative pathology indicated malignant nodules in 15 cases and benign nodules in 2 cases; in 2 cases of unilateral thyroid lobectomy, the mean operation time was (153.5±34.64) min; in 15 cases of unilateral thyroid lobectomy with central lymph node dissection, the mean operation time was (123.73±14.26) min; and none of patients developed postoperative neck infections or CO(2) gas embolism. All patients had different degree of cutaneous numbness in the submandibular region after surgery, which recovered within 1-2 weeks. There were no complications such as postoperative secondary hemorrhage, permanent vocal cord paralysis, hypoparathyroidism in both the periods. The median follow-up time was 86 months (57-105 months) in Peroid A and 5 months (3-12 months) in Peroid B. During the follow-up periods, there were no obvious abnormalities in swallowing, chewing, oral sensory function and neck activity, and also no tumor recurrence or metastasis. Conclusions: TOETSLVA is a safe and feasible surgery method, with a good cosmetic result. This approach will not lead to a postoperative cutaneous numbness of the submandibular region for a long time.

Structure and expression of the promoter for the R4/ALK5 human type I transforming growth factor-beta receptor: regulation by TGF-beta.

The type I transforming growth factor-beta (TGF-beta) receptors are serine/threonine kinases that are essential for the action of TGF-beta. In this paper, we describe the molecular cloning and expression of the R4/ALK5 human type I TGF-beta receptor promoter. DNA sequence analysis indicates that the promoter lacks a TATA and CAAT box but is highly GC-rich and contains putative Sp1 binding sites. The transcriptional start site is approx. 232 base pairs upstream of the AUG start codon. In human lung fibroblasts, TGF-beta induced a 3-fold increase in steady-state level for type I receptor mRNA. Exposure of cells transfected with a 618 bp promoter fragment to TGF-beta 1 up-regulated transcriptional activity indicating that a TGF-beta response element is contained within this region.

Imatinib-based therapy in adult Philadelphia chromosome-positive acute lymphoblastic leukemia: A case report and literature review.

Acute lymphoblastic leukemia (ALL) has a rapid onset and rarely occurs with exclusive prodrome of general osteoporosis and vertebral compression fractures. However, Philadelphia chromosome-positive (Ph+) ALL has a poor prognosis, even when patients are treated with intensive chemotherapy, and the first-line effective treatment requires further elucidation. The present study focused on a 56-year-old Chinese male patient who initially presented with spontaneous bone fractures and was ultimately diagnosed as Ph+ ALL after 6 months, which required to preliminarily exclude a working diagnosis of myeloma. Apart from intensive chemotherapy, the patient successfully completed an imatinib-based regimen and achieved complete remission (CR) 2 weeks later. Subsequently, the patient was subjected to consolidation treatment using the same imatinib regimen combined with interferon-α 2b for 9 courses. In November 2013, the patient had achieved persistent hematological and molecular genetic normality for ~16 months after the initial CR. In conclusion, Ph+ ALL must be considered in the differential diagnosis of adults experiencing unexplained bone disease.

Apigenin decreases expression of the myofibroblast phenotype.

We investigated the effect of the dietary flavonoid apigenin on myofibroblast function. We report that in myofibroblasts treated with apigenin, proliferation and basal levels of alpha1(I) collagen and alpha-smooth muscle actin mRNAs were markedly reduced. Apigenin also attenuated the transforming growth factor-beta-stimulated increases of alpha1(I) collagen and alpha-smooth muscle actin mRNAs. Characterization of the apigenin effects indicates that apigenin reduces both the stability of the alpha1(I) collagen mRNA and the rate of transcription of the alpha1(I) collagen gene through a cycloheximide-sensitive pathway. Western blot analyses indicate that Akt activity is reduced in apigenin-treated myofibroblasts.

Reversed effects of RU486 and anisomycin on memory retention of light exposure or corticosterone facilitation in the dark-incubated chicks.

Memory formation for a weak passive avoidance task in the dark-incubated chicks is facilitated by light exposure or corticosterone administration at optimally pre-hatch time points. To explore the potential mechanisms underlying activation of brain memory function development by light or corticosterone exposure during late embryo, steroid receptor antagonist RU486, or protein synthetic inhibitor anisomycin, was administered intraembryonically to the embryos of either only 24-h light-exposure or complete dark-hatched on embryonic day 20 (E20). The results showed that RU486 and anisomycin significantly retarded the facilitated retention both by light and corticosterone exposure in the dark-incubated chicks. They also suggest that the act of corticosterone or light exposure on the development of brain memory function is mediated by the effect of steroid receptor, or afterward on related protein syntheses that is involved in memory formation of post-hatched performance of day-old chicks.

Cerebral infarction improved by safflower treatment.

The effect of safflower on cerebral infarction was studied in 152 Mongolian gerbils. Sixty-three animals were evaluated neurological deficit over 8 hours postoperation, then sacrificed and NE, DA and 5-HT contents of each cerebral hemisphere and brain stem were determined. NE, DA and 5-HT of hemisphere ipsilateral to the ligated artery in untreated animals declined significantly compared with sham-operated animals and safflower-treated gerbils. There was no significant difference between safflower-treated and sham-operated animals in NE, DA and 5-HT contents. The mean stroke index at 8 hours in safflower treated animals was 2.1 +/- 0.7, whereas untreated gerbils was 7.8 +/- 1.9 (P less than 0.01). Eighty-nine animals were followed up for 5 days, the safflower-treated animals showed a benign clinical course and mortality rate was reduced by 29.7% (6/34 vs. 26/55) in safflower-treated animals compared with untreated animals (P less than 0.01). Safflower has a protective and beneficial effect on cerebral ischemia induced in Mongolian gerbils.

Changes of endothelin-1 gene expression in rat brains during ischemia and ischemic reperfusion.

OBJECTIVE: The experiment was designed to study the association of cerebral ischemia and reperfusion with endothelin-1 (ET-1) gene expression of rat brains and time-dependent changes of ET-1 gene expression during cerebral ischemia. MATERIALS AND METHODS: Thirty-three male SD rats were divided into dot blot hybridization (n = 27) and in situ hybridization groups (n = 6). The focal cerebral ischemia and reperfusion models were made with suture embolism of middle cerebral artery. Dot blot hybridization groups were redivided into control and ischemic subgroups (ischemia for 0.5, 1, 1.5, 3, 6, 12, 24, 48 and 72 h respectively). In situ hybridization groups were redivided into ischemia and reperfusion groups. After 24 h ischemia and 24 h reperfusion, ET-1 gene expressions were investigated with in situ hybridization and the results were analyzed with IBAS 2000 Image Analysis System. RESULTS: Dot blot hybridization showed that ET-1 mRNA of cerebral cortex and caudate-putamen was increased at 6 h of ischemia and reached peak at 24 h (3.9 and 3.7 fold respectively), and at 72 h of ischemia it remained at high levels (3.5 and 2.1 fold respectively). In situ hybridization showed that the levels of ET-1 mRNA of cerebral cortex and caudate-putamen were also markedly increased both in 24 h ischemia and 24 h reperfusion groups (P < 0.01, P < 0.05 respectively). CONCLUSIONS: ET-1 gene expression in focal ischemic brain tissue were markedly and progressively increased during cerebral ischemia and reperfusion and down-regulation of ET-1 gene expression may be a new approach to the treatment of ischemic cerebrovascular diseases.

Studies of qingyangshen (I): Differential expression of hippocampal c-fos proto-oncogene during kainic acid induced acute and chronic seizures.

We previously reported that Qingyangshen (QYS), a traditional Chinese medicine with antiepileptic property, had therapeutic effect on kainic acid (KA) induced experimental seizures (see JTCM 13 (4): 281-286, 1993 for reference). To investigate the mechanisms underlying the anticonvulsant action of QYS, we analyzed the modulatory effect of QYS on rat hippocampal c-fos proto-oncogene expression during KA-induced epileptogenesis in this and the following paper. The expression of hippocampal c-fos gene during KA-induced seizures were examined first. Rats were intraperitoneally injected with kainic acid (KA, 12 mg/kg) and hippocampal c-fos mRNA level was determined by Northern blot analysis during both acute (within one day after KA injection) and chronic (15 days after KA treatment) seizures. A mild increase in hippocampal c-fos mRNA level was observed 30 min after KA injection (being 1.98 +/- 0.70 times of control level), which corresponded temporally to the occurrence of the first limbic seizures. There was an 11.02 +/- 3.33 fold maximal induction of c-fos mRNA at 2 h after KA administration, which remained relatively stable even when behavioral seizures continued to aggravate 4 h after KA treatment. Twelve hours after KA administration, c-fos mRNA in the hippocampus returned to control level when acute seizures began to gradually disappear. In contrast, the induction of hippocampal c-fos mRNA during chronic seizures was inhibited significantly, being reduced by 55.40% compared to control. This suggested that c-fos is in different functional states at acute and chronic stages of epileptogenesis induced by KA.

Effect of radix salviae miltiorrhizae on EAA and IAA during cerebral ischemia in gerbils: a microdialysis study.

The concentrations of amino acids (AA), stroke index and infarct area were determined in 26 gerbils which were divided into 3 groups: RSM-treated (n = 8), Saline-treated (n = 10) and sham-operated (n = 8). The levels of AA were measured with microdialysis technique in cerebral cortex. The concentrations of neurotransmitter AA, as Glu and GABA and Asp, were significantly increased during the first 60 min after CCA ligation, while the concentrations of non-neurotransmitter AA, as Thr and Ser, had no significant changes. In RSM-treated gerbils, the level of Glu was significantly lower than that of the saline-treated, but the GABA in RSM-treated was significantly higher than that of the saline-treated. The ratio of Glu/GABA was significantly decreased after ischemia. The RSM could improve the reduction of ratio of Glu/GABA during 0-30 min and 91-120 min after cerebral ischemia. There were statistically significant decrease in terms of stroke index in RSM-treated group when compared with saline-treated group at 24 h and 16 h after CCA ligation respectively. The RSM has a tendency to decrease the size of infarct area, but no statistical difference. The results suggest that the neurotransmitter AA involve in the pathophysiological procedures of cerebral ischemia and the RSM can attenuate dysfunctions of EAA and IAA. Furthermore, the results also imply that there may be an alternate way to treat cerebral ischemia by inhibiting the presynaptic releasing of Glu and stimulating the releasing of GABA.

Studies of Qingyangshen (II): modulatory effect of co-treatment with qingyangshen and diphenylhydantoin sodium on rat hippocampal c-fos expression during seizures.

We have reported that, after KA treatment in rats, there was first a significant increase in hippocampal c-fos expression during acute seizures and then a long-term inhibition in hippocampal c-fos expression during chronic seizures. In this experiment, we examined the modulatory effect of Qingyangshen (QYS), a traditional Chinese medicine with antiepileptic property, and diphenylhydantoin sodium (DPH) on hippocampal c-fos expression during seizures. We found that after intraperitoneal injection of QYS + DPH (15 mg/kg and 50 mg/kg respectively, q.o.d. x 6), the peak level of hippocampal c-fos mRNA induction during KA-induced acute seizures was reduced by 56.27%; while the inhibition of hippocampal c-fos expression during KA-induced chronic seizures was disinhibited to control level. It is suggested that the inhibitory effect of QYS + DPH on KA-induced seizures, chronic seizures in particular, may have much to do with its modulatory effect on hippocampal c-fos expression.

Effect of qingyangshen on hippocampal alpha- and beta-tubulin gene expression during kainic acid induced epileptogenesis.

Using alpha- and beta- tubulin cDNA Probes and Northern blot hybridization technique, we analyzed the effect of intraperitoneally injected Qingyangshen (QYS), a traditional Chinese medicine with antiepileptic property, and diphenylhydrantoin sodium (DPH) on hippocampal alpha- and beta-tubulin gene expression during kainic acid (KA) induced chronic seizures. It was found that: 1) thirty days after intraperitoneal injection of KA, alpha- and beta-tubulin mRNAs in animals showing chronic seizures increased 3.02 +/- 1.05 and 4.07 +/- 1.32 times respectively compared with control; 2) neither QYS (15 mg/kg, q.o.d. x 6) nor DPH (50 mg/kg, q.o.d. x 6), when used separately, could inhibit the above mentioned effect of KA; 3) when QYS (15 mg/kg, q.o.d. x 6) and DPH (50 mg/kg, q.o.d. x 6) were given in combination, the long-term increase in tubulin gene expression induced by KA was significantly reduced, with alpha- and beta-tubulin mRNAs being decreased to 0.44 +/- 0.08 and 0.50 x 0.10 times of corresponding values in animals treated with KA alone. The results indicate that the mechanism of antiepileptic effect of QYS is at least partially related to the inhibition of tubulin synthesis and subsequent reduction in mossy fiber sprouting and neosynaptogenesis.

Evidence for amelioration of cellular damage in ischemic rat brain by radix salviae miltiorrhizae treatment--immunocytochemistry and histopathology studies.

The changes of somatostatin (SS)--like immunoreactive cells and morphology were observed in the models of ligation of right MCA and bilateral ligation of CCA respectively. The results showed: (1) a decline of SS immunoreactive nerve cell profiles in right cerebral cortex after 3h ligation of MCA as compared with left cerebral cortex and sham-operated group, while no significant difference was found between RSM-treated and saline-treated groups; (2) selective ischemic cell changes in cerebral cortex, hippocampus and caudate nucleus after 3h ligation of CCA. The changes included shrinkage and condensation of perikaryon, nuclear pyknosis, cytoplasmic eosinophilia in some neurons. The ischemic changes were more severe in saline-treated group than RSM-treated group. The experiments indicated that the selective ischemic cell changes could be improved by RSM, suggesting that treatment to modulate SS metabolism may be indicated after ischemic insults.

Effect of radix Salviae miltiorrhizae on the gene expression of nitric oxide synthase in ischemic rat brains.

The effect of Radix Salviae Miltiorrhizae (RSM) on the gene expression of nitric oxide synthase (NOS) in rat brains during ischemia was studied with in situ hybridization and the results were analyzed with IBAS 2000 Image Analysis System. It was found that NOS gene expression of cerebral cortex and caudate-putamen was markedly increased in 24 hours in ischemia group (P < 0.01). In RSM-treated rats, although the NOS gene expression of ischemic side was also increased as compared with contralateral cortex and caudate-putamen, it was significantly lower in RSM-treated rats than those of the controls (P < 0.05, P < 0.01). The present study indicates that RSM can partly inhibit NOS gene expression of cerebral cortex and caudate-putamen during ischemia. This may be one of the protective mechanisms of RSM on cerebral ischemia.

Effect of radix Salviae miltiorrhizae on extracellular adenosine and evaluation of its protective efficacy in ischemic reperfusion rat--microdialysis, HPLC and histopathologic studies.

The effects of Radix Salviae Miltiorrhizae (RSM) on extracellular adenosine (Ade) and its metabolites, i.e. inosine, hypoxanthine and xanthine, were studied with microdialysis and HPLC techniques during cerebral ischemia-reperfusion induced by 4-vessel occlusion in rat brain. Histological examination of hippocampus was performed 6 h after reperfusion. ECF (extracellular fluid) adenosine and its metabolites were compared between the controls (n = 6) and RSM-treated rats (n = 6). Basal level of Ade and its metabolites release were not greatly affected by pretreatment with RSM, and no significant difference as compared with the sham-operated (n = 6). Ade and its metabolites were dramatically increased after ischemia, and decreased near basal-level and its metabolites remained high at the end of reperfusion. In the RSM-treated animals, the tendency of changes of Ade and its metabolites was just the same as in the controls, but the magnitudes of changes were significantly lower at some different time points. In sham-operated animals, no changes were observed at different time points both during ischemia (30 min.) and reperfusion (60 min.). Histopathological findings demonstrated that RSM pretreatment results in better histologic preservation of the pyramidal cells in the postischemic reperfusion CA1 sector both qualitatively and quantitatively. These results indicated that RSM protects against cerebral ischemia reperfusion injury.

Protective effect of radix Salviae miltiorrhizae on apoptosis of neurons during focal cerebral ischemia and reperfusion injury.

We have found that Radix Salviae Miltiorrhizae (RSM) plays a protective role in ischemic brain injury, which attracted us to investigate the effect of RSM on apoptosis of neurons during cerebral ischemia and reperfusion. The apoptotic cells in ischemic brains at different reperfusion intervals were tested with the method of TdT-mediated dUTP-DIG nick end labeling (TUNEL), and the effect of RSM on the apoptosis of neurons was studied in left middle cerebral artery (LMCA) occlusion in rat models (n = 18). The results showed that few scattered apoptotic cells were observed in right cerebral hemisphere after LMCA occlusion and reperfusion, and that a lot of apoptotic cells were found in left ischemic cerebral cortex and caudoputamen at 12 h reperfusion, and they reached peak at 24-48 h reperfusion. However, in rats pretreated with RSM, the number of apoptotic cells in left cortex and caudoputamen reduced significantly and the neuronal damage was much milder at 24 h reperfusion as compared with those of saline-treated rats. From this study, we conclude that administration of RSM can reduce the apoptotic of neurons induced by cerebral ischemia and reperfusion and afford significant cerebroprotection in the model of focal cerebral ischemia and reperfusion.