Search

Minocycline is a second-generation, semi-synthetic tetracycline, and has broad spectrum-antibacterial activity. Interestingly, many studies have demonstrated that minocycline is beneficial for depression, which may be due to its effects on neuroinflammation modulation. Recently, gut microbiota imbalance has been found in depression patient and animal models. Based on the fact of minocycline usually acting as an antibiotic and the relationship between depression, gut microbiota, and neuroinflammation, we designed this study to detect the effects of chronic minocycline treatment on antidepression, neuroinflammation, and gut microbiota modulation. Our results showed that minocycline treatment for 4 weeks, not acute treatment, exerted antidepressant effect in mice exposed to unpredictable chronic mild stress (CUMS). Further results suggested that chronic minocycline treatment inhibited neuroinflammation of hippocampus and altered species abundance and metabolites of gut microbiota. Meantime, we found that chronic minocycline treatment ameliorated intestinal barrier disruption and reduced the bacteriological indexes, such as diamine oxidase, C-reaction protein, and endotoxin in peripheral blood of CUMS mice. To sum up, our findings confirm that chronic minocycline treatment exerts the antidepressant effect, inhibits neuroinflammation, and modulates gut microbiota. All of these imply that the antidepressant mechanism of chronic minocycline treatment is maybe due to the combined action of neuroinflammation and gut microbiota modulation, which need further prospective studies.

Purpose The aim of this work was to evaluate the prognostic value of tumor length and diameter for patients with esophageal squamous cell cancer (ESCC) treated with definitive (chemo)radiotherapy to identify potential indicators for separate nonsurgical T staging, which are needed in clinical practice. Materials and Methods A total of 682 patients with ESCC who underwent definitive (chemo)radiotherapy between 2009 and 2015 were reviewed. Esophageal tumor length and diameter were determined by barium esophagography and computed tomography before treatment. Univariate and multivariate analyses were used to assess the impact of tumor length and diameter on long‐term overall survival (OS) and progression‐free survival (PFS). Propensity score matching (PSM) analysis was also used to control intergroup heterogeneity. Results The median OS and PFS were 22.2 months and 15.4 months, respectively, in the tumor length ≤ 6 cm group, which were significantly longer than those in the tumor length > 6 cm group (13.4 and 8.5 months, respectively). The median OS and PFS were 23.3 months and 15.9 months, respectively, in the tumor diameter ≤ 3.5 cm group, which were also significantly longer than those in the tumor diameter > 3.5 cm group (13.3 and 8.8 months, respectively). Similar results were found after PSM. Univariate and multivariate analyses showed that tumor length and diameter were both independent predictors of long‐term survival. Conclusion Tumor length and diameter are both independent prognostic factors for ESCC patients treated with definitive (chemo)radiotherapy. These two imaging parameters have the potential for development and use in nonsurgical T staging., Tumor length and diameter are both independent prognostic factors for esophageal squamous cell cancer patients treated with definitive (chemo)radiotherapy. These two imaging parameters have the potential to develop nonsurgical T staging.

This study aimed to investigate the effects of CYP2C19 metabolizer status on the clinical therapeutic efficacy of cerebral infarction. Patients with cerebral infarction ( n = 180; NIHSS score ≤ 5) were recruited and divided into Group A and Group B according to CYP2C19 metabolizer status. In Group A, patients received routine clopidogrel therapy for 1 year; in Group B, the patients with extensive metabolizer (EM) were treated with clopidogrel, and patients with intermediate metabolizer (IM) and poor metabolizer (PM) were treated with aspirin for 1 year. On admission, National Institutes of Health Stroke Scale score was determined, and the therapeutic efficacy was evaluated with Modified Rankin Scale score after 1 year of treatment. The outcomes and adverse effects were recorded during the treatment. After routine clopidogrel treatment, the efficacy in EM patients was significantly better than in PM and IM patients. After adjustment of therapeutic protocol, the therapeutic efficacy in PM and IM patients was markedly improved, which was accompanied by significant reduction in recurrence rate of cerebral infarction. Although the adverse effects increased in patients receiving aspirin treatment, they resolved after symptomatic therapy. CYP2C19 metabolizer status is closely related to the clinical efficacy of clopidogrel. Thus, it is necessary to adjust the anti-platelet treatment according to the CYP2C19 metabolizer status to maximize therapeutic efficacy without increasing recurrence and adverse effects.

Background The impact of sex on prognosis of patients with esophageal squamous cell cancer (ESCC) who underwent definitive radiotherapy remained unclear. The present study aimed to determine the impact of sex on the prognosis of patients with ESCC underwent definitive radiotherapy. Methods Between January 2009 and December 2015, patients with ESCC underwent definitive radiotherapy in Shantou Central Hospital were included in this study. The Progression-free survival (PFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. The PFS and OS were compared between female and male patients. The Cox regression model was used to identify prognostic factors. Propensity score-matched analysis was performed to balance baseline characteristics between female and male patients. Results A total of 683 ESCC patients treated with definitive radiotherapy were included, with 497 male and 186 female patients. In the whole cohort, female patients had a significantly longer median PFS (14.0 months vs 10.6 months, P = 0.0001, HR = 0.688, 95% CI, 0.567–0.836) and OS (20.8 months vs 15.9 months, P = 0.0005, HR = 0.702, 95% CI, 0.575–0.857). In the matched cohort, female patients still had a significantly longer median PFS (13.5 months vs 11.6 months) and OS (19.6 months vs 16.1 months). Multivariate analysis showed that sex was an independent prognostic factor for PFS (HR = 0.746, 95% CI, 0.611–0.910, P = 0.004) and OS (HR = 0.755, 95% CI, 0.615–0.926, P = 0.007). Conclusions This present study indicated that sex was an independent prognostic factor in Chinese patients with ESCC underwent definitive radiotherapy, with better survival outcome for women than men. Efforts should be made to investigate the underlying biological mechanism. Electronic supplementary material The online version of this article (10.1186/s13014-019-1278-0) contains supplementary material, which is available to authorized users.

To investigate the expressions of HSF1 and tetra-hydroxynonene (4-HNE) in prostate cancer (PCa) tissue and their clinical significance.Using the immunohistochemical method, we detected the expressions of HSF1 and 4-HNE in the prostatic tissues of 50 cases of PCa and another 50 cases of BPH, and analyzed the relationship of the two expressions with Gleason grade.The positive expression level of HSF1 was dramatically higher in the highly, moderately and lowly differentiated PCa than in the BPH tissue (37.5%, 50.0% and 75.0% vs 4.0%, P = 0.001) and showed statistically significant difference among different Gleason grades (P = 0.025), so was that of 4-HNE (81.3%, 92.9% and 100.0% % vs 6.0%, P = 0.001), also with statistically significant difference among different Gleason grades (P = 0.029). There was a positive correlation between the expression of HSF1 and that of 4-HNE in the PCa tissue (r = 0.947, P = 0.001).The overexpressions of HSF1 and 4-HNE are related to the Gleason grades of prostate cancer, which can be used as an new biological marker with important reference value for assessing the malignancy of prostate cancer.

Purpose To develop and validate a nomogram model to predict complete response (CR) after concurrent chemoradiotherapy (CCRT) in esophageal squamous cell carcinoma (ESCC) patients using pretreatment CT radiomic features. Methods Data of patients diagnosed as ESCC and treated with CCRT in Shantou Central Hospital during the period from January 2013 to December 2015 were retrospectively collected. Eligible patients were included in this study and randomize divided into a training set and a validation set after successive screening. The least absolute shrinkage and selection operator (LASSO) with logistic regression to select radiomics features calculating Rad-score in the training set. The logistic regression analysis was performed to identify the predictive clinical factors for developing a nomogram model. The area under the receiver operating characteristic curves (AUC) was used to assess the performance of the predictive nomogram model and decision curve was used to analyze the impact of the nomogram model on clinical treatment decisions. Results A total of 226 patients were included and randomly divided into two groups, 160 patients in training set and 66 patients in validation set. After LASSO analysis, seven radiomics features were screened out to develop a radiomics signature Rad-score. The AUC of Rad-score was 0.812 (95% CI 0.742–0.869, p p = 0.003) in the validation set. Multivariate analysis showed that Rad-score and clinical staging were independent predictors of CR status, with p values of 0.035 and 0.023, respectively. A nomogram model incorporating Rad-socre and clinical staging was developed and validated, with an AUC of 0.844 (95% CI 0.779–0.897) in the training set and 0.807 (95% CI 0.691–0.894) in the validation set. Delong test showed that the nomogram model was significantly superior to the clinical staging, with p p = 0.026 in the validation set. The decision curve showed that the nomogram model was superior to the clinical staging when the risk threshold was greater than 25%. Conclusion We developed and validated a nomogram model for predicting CR status of ESCC patients after CCRT. The nomogram model was combined radiomics signature Rad-score and clinical staging. This model provided us with an economical and simple method for evaluating the response of chemoradiotherapy for patients with ESCC.

Summary: Background: To compare overall survival in patients with clinical T1-3N0-1 thoracic esophageal squamous cell carcinoma treated with surgery or definitive chemoradiation therapy (CRT). Methods: We used propensity-score matching to derive 1:1 cohorts of surgery versus definitive CRT. Statistical analysis was performed using χ2 or Fisher's exact tests. Survival functions were estimated using Kaplan–Meier survival plots, and survival distributions were compared using log-rank tests. Cox proportional hazards modeling was used to analyze the factors affecting overall survival. Results: A total of 334 patients treated with surgery and 252 treated with definitive CRT were included. 129 (38.6%) of 334 patients had recurrence after surgery versus 118 (46.8%) of 252 after definitive CRT. Before matching, the median overall survival were 39.5 months (95% CI, 28.8–50.2) and 23.5 months (95% CI, 18.5–28.5) (P

Background The prognostic value of supra-clavicular lymph node (SCLN) metastases in esophageal cancer (EC) is still not clear. Method From January 2009 to December 2015, a survival analysis was performed to retrospectively identify the prognostic value of SCLN metastasis on survival on 751 patients with EC treated with definitive chemo-radiotherapy (dCRT). Results The median follow-up duration for living patients was 56.6 months. The median overall survival (OS) for all patients was 16.6 months. Patients with SCLN metastasis had a much poorer prognosis for OS (χ 2 = 17.342, P

Proximal spinal muscular atrophy (SMA) is a common fatal autosomal recessive disorder caused by deletion or mutation of the survival of motor neuron 1 (SMN1). Here, we studied SMA molecular pathology in 653 Chinese patients and found approximately 88.2% with homozygous SMN1 exon 7 deletion and 6.3% with heterozygous exon 7 loss using multiplex ligation-dependent probe amplification. SMN1 variants were detected in 34 patients with heterozygous SMN1 loss by clone sequencing. In 27 of them, 15 variants were identified: five were unreported novel variants [c.-7_9del(p.0), p.Tyr109Cys, p.Ile249Tyrfs*16, p.Tyr272Trpfs*35, and c.835-5T>G], five were previously found only in Chinese patients (p.Ser8Lysfs*23, p.Gln14*, p.Val19Glyfs*21, p.Leu228*, and p.Tyr277Cys), and five were reported in other populations [p.Ala2Gly, p.Gln15*, p.Glu134Lys, p.Ser230Leu, and c.863G>T (r.835_*3del, p.Gly279Glufs*5)]. Variants p.Ser8Lysfs*23 and p.Leu228* were the most common in Chinese SMA. Five variants (p.Ser8Lysfs*23, p.Gln14*, p.Gln15*, p.Val19Glyfs*21, and p.Leu228*) resulted in premature stop codons, likely causing SMN1 mRNA nonsense-mediated decay. The novel variant c.-7_9del (p.0) caused deletion of the translation start codon (AUG), resulting in full-length SMN protein loss. The novel variant c.835-5T>G, located in a splice site, resulted in 90% exon 7 skipping. Our study could facilitate early diagnosis for SMA patients in mutation detection and revealed the specific mutation spectrum of SMN1 in Chinese SMA and high genetic heterogeneity in subtle variants observed between patients from China and Caucasians.

To investigate the expressions of glutathione S-transferase (GSTP1) and tetra-hydroxynonenal (4-HNE) in prostate cancer (PCa) and their clinical significance.We determined the expressions of GSTP1 and 4-HNE in 40 patients with PCa and another 42 with benign prostatic hyperplasia (BPH) by immunohistochemistry and analyzed their relationship with Gleason grades.The expression rate of GSTP1 was 92.9% in the BPH tissue, and those in the highly, moderately, and lowly differentiated PCa tissues were 58.3%, 20.0%, and 16.7%, respectively, significantly higher in the BPH than in the PCa group (P0.01). However, the positive rate of 4-HNE was only 5.0% in the BPH tissue, markedly lower than 91.6%, 100.0%, and 100.0% in the highly, moderately, and lowly differentiated PCa tissues (P0.01). There was a negative correlation between the expression of GSTP1 and that of 4-HNE in the PCa tissue (r = －2.73, P0.01).Expression deletion of GSTP1 and high expression of 4-HNE may play an important role in the progression of prostate cancer.目的： 探讨谷胱甘肽S转移酶P1（GSTP1）和四羟基壬烯(4-HNE)在前列腺癌组织中的表达及其临床意义。方法： 采用免疫组化方法检测40例前列腺癌组织及42例BPH组织中GSTP1和4-HNE 的表达，分析GSTP1和4-HNE的表达与Gleason分级之间的关系。结果： GSTP1在BPH组织中为高表达(92.9%)，40例前列腺癌组织中GSTP1表达率在高、中、低分化癌中分别为58.3%、20.0%、16.7%，呈下降趋势，两组GSTP1表达差异有统计学意义（P0.01）。4-HNE在前列腺增生组织中阳性表达率较低，仅为5.0%。40例前列腺癌组织中4-HNE高表达，在高、中、低分化癌中分别为91.6%、100.0%、100.0%，呈明显上升趋势，两组4-HNE表达差异有统计学意义（P0.01）。前列腺癌组织中GSTP1和4-HNE阳性表达呈负相关（r=－2.73，P0.01）。结论: GSTP1表达缺失和4-HNE的高表达，可能在前列腺癌的进展中起重要作用。.

Background Chylothorax after esophagectomy is uncommon but potentially fatal. We performed a retrospective study to assess the effect of olive oil administered orally before surgery on reducing chylothorax in patients who underwent minimal invasive esophagectomy. Methods Between May 2013 and December 2016, patients with esophageal squamous cell cancer who underwent minimal invasive esophagectomy were screened. Patients in the investigational group were preoperatively administered olive oil orally 8 hours before surgery, and patients in the control arm received no olive oil. We used a propensity score matching model to derive 1:1 cohorts. Statistical analysis was performed by using the t test or χ2 or Fisher’s exact test. Results The propensity score matching model finally selected 384 of 425 patients, with 192 patients in each group. The patient characteristics were balanced. Oral olive oil was well tolerated. The thoracic duct identification rate was higher in the investigational group (100% versus 45.31%, χ2 = 141.78, p Conclusions Preoperative administration of olive oil is a simple and safe method to minimize chylothorax complicating minimal invasive esophagectomy.

Definitive chemoradiotherapy (dCRT) is a treatment option for patients with localized esophageal squamous cell carcinoma (ESCC). We investigated consolidation chemotherapy (CCT) in patients with ESCC who attained clinical complete response after dCRT. Between January 2009 and December 2012, medical records of ESCC patients treated with dCRT were retrospectively reviewed, and those who attained CCR were identified. Progression-free survival and overall survival rates were estimated by the Kaplan-Meier method. The Cox regression model was used to determine prognostic factors. Of the 522 patients treated with dCRT, 209 patients achieved CCR, with 67 receiving consolidation chemotherapy (the CCT group) and 142 receiving dCRT alone (the control group). CCT did not prolong progression-free survival (33.0 vs 18.0 months, P = 0.07, HR = 0.70, 95% CI, 0.48–1.04); however, CCT improved the median overall survival (53.4 vs 27.0 months, P = 0.04, HR = 0.67, 95% CI, 0.44–0.99) compared with dCRT alone. CCT remained a favorable prognostic factor for overall survival in a multivariate analysis (HR = 0.59, P = 0.02); however, a propensity score analysis failed to show an additional overall survival benefit with CCT. In the present analysis, CCT did not improve progression-free survival but may have extended overall survival in ESCC patients who achieved complete clinical response after dCRT.

Summary Aims Mounting evidence showed that GABAergic interneurons play an important role in the generation of seizures by regulating excitatory/inhibitory balance in the hippocampus; however, there is a continuous debate regarding the alteration in the number of hippocampal GABAergic interneurons during epileptogenesis. Here, we investigated the degeneration and regeneration of GABAergic interneurons in the dentate gyrus during epileptogenesis using glutamic acid decarboxylase-green fluorescence protein (GAD67-GFP) knock-in mice. Methods and Results Pentylenetetrazol (PTZ)-induced chronic kindling model and lithium–pilocarpine-induced status epilepticus (SE) model were used in this study. We found a progressive loss of GABAergic interneurons in the dentate gyrus during post-SE epileptogenesis rather than PTZ kindling. Both types of epileptogenic insults significantly promoted the proliferation of neural progenitor cells in the dentate gyrus; however, compared to 80% neuronal differentiation ratio in the control group, there was a remarkable decrease in PTZ kindling and pilocarpine models, that is 58% and 29%, respectively. Double/triple immunofluorescence labeling revealed no newborn neurons colabeled with GFP in both intact and epileptic dentate gyrus. In addition, valproate (a first-line antiepileptic drug) treatment prevented the loss of GABAergic interneurons but still failed to induce the regeneration of GAD67-positive interneurons in the dentate gyrus during post-SE epileptogenesis. Conclusions These results indicate that degeneration of GABAergic interneurons may depend on the type of epileptogenic insult and that no newborn GABAergic interneurons occur in the adult dentate gyrus during epileptogenesis.

To observe the intervention and mechanism of Qushi Huayu Recipe (QHR) on gene expression profiles in high lipid diet induced fatty liver rats.Fatty liver model was prepared in 20 male SD rats using single high fat diet (88% common forage +2% cholesterol +10% lard). Four weeks after modeling they were divided into the model group and the QHR group according to random digit table, 10 in each group. QHR (at 0. 93 g crude drug/100 g body weight) and distilled water was respectively to rats in the QHR group and the model group by gastrogavage while modeling, once per day. Meanwhile, 10 SD male rats were recruited in a normal group, administered with equal volume of distilled water by gastrogavage. At the end of week 8 all rats were sacrificed, and blood and livers were collected for subsequent analysis. Contents of liver triglyceride (TG) and free fatty acid (FFA) , activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using biochemical assay. Pathological changes of liver tissue were observed using HE and oil red O stain. Liver gene expressions were detected by Affymetrix gene expression profiles. Differentially expressed genes were compared between the QHR group and the model group, functions of differentially expressed genes and signal pathways involved analyzed. Ten differentially expressed genes involved in glycolipid metabolism with fold change more than 2 were selected for verification by real-time PCR.(1) Compared with the normal group, contents of liver TG and FFA, and serum activities of ALT and AST obviously increased in the model group (P0. 01). Compared with the model group, contents of liver TG and FFA, and activities of ALT and AST obviously decreased in the QHR group (P0. 05, P0. 01). QHR could reduce high fat induced fatty degeneration of liver cells , alleviate inflammation, and improve pathological changes of liver tissue. (2) Compared with the model group, there were 80 differentially expressed genes (with fold change2, P0.05) with clear functions and appointed gene names, including 44 up-regulated and 36 down-regulated genes. Eighty genes were involved in 27 signal pathways with statistical difference, including glycerolipid metabolism, adipocytokine signaling pathway, insulin signal pathway, drug metabolism signal pathway, etc (P0.05). (3) RT-PCR results of 10 glycolipids metabolism regulating genes such as Gk, Scd1, Gpat2, G6pc, Irs1, and so on showed that all RT-PCR genes were completely coincide with up-regulated or down-regulated tendency in results of gene chips. 80% genes had approximate fold change.QHR could regulate gene expressions related to fat metabolism, carbohydrate metabolism, anti-lipid peroxidation, and drug metabolism in high fat diet induced fatty liver rats, and its comprehensive pharmacological actions could be manifested.

The homozygous loss of the survival motor neuron 1 (SMN1) gene is the primary cause of spinal muscular atrophy (SMA), a neuromuscular degenerative disease. A genetically similar gene, SMN2, which is not functionally equivalent in all SMA patients, modifies the clinical SMA phenotypes. We analyzed the methylation levels of 4 CpG islands (CGIs) in SMN2 in 35 Chinese children with SMA by MassARRAY. We found that three CpG units located in CGI 1 (nucleotides (nt) -871, -735) and CGI 4 (nt +999) are significantly hypomethylated in SMA type III compared with type I or II children after receiving Bonferroni correction. In addition to the differentially methylated CpG unit of nt -871, the methylation level of the nt -290/-288/-285 unit was negatively correlated with the expression of SMN2 full-length transcripts (SMN2-fl). In addition, the methylation level at nt +938 was inversely proportional to the ratio of SMN2-fl and lacking exon 7 transcripts (SMN2-Δ7, fl/Δ7), and was not associated with the SMN2 transcript levels. Thus, we can conclude that SMN2 methylation may regulate the SMA disease phenotype by modulating its transcription.

This study is to investigate the therapeutic effects of the recipe composed ofAtractylodes macrocephalapolysaccharide, chlorogenic acid, and geniposide (named ACG) on experimental nonalcoholic fatty liver (NAFL). The research was divided into two parts as screening experiment and verification experiment. In the screening experiment, we used high-fat diet (HFD) induced NAFL rat model and uniform design to get the recipe from five Chinese herbal active components. In the verification experiment, HFD induced fatty liver rat and mouse NAFL models and free fatty acid (FFA) induced HepG2 cell model were used to verify the effects of ACG. According to the multiple regression equation of the hepatic triglyceride (TG) contents of each group in the screening experiment, the recipe ACG was obtained and the doses ofAtractylodes macrocephalapolysaccharide, chlorogenic acid, and geniposide for rats were 266.67, 3.33, and 45 mg/kg, respectively. The results of verification experiment verified that ACG could significantly reduce hepatic TG contents of NAFL rats and mice, as well as the cellular TG content of FFA-induced HepG2 cells. ACG could also improve HOMA-IR and hepatic mitochondrial ultrastructure of NAFL mice. Our study verified that ACG recipe could regulate lipid metabolism of NAFLin vivoandin vitro.

Previous studies had shown that CXC chemokine ligand-12 (CXCL12) might play a significant role in stroke. The aim of this study was to test the serum baseline CXCL12 levels in Chinese patients with acute ischemic stroke (AIS).All consecutive patients with first-ever AIS from January 2013 to June 2014 were recruited to participate in the study. CXCL12 and National Institutes of Health Stroke Scale were measured at the time of admission. Logistic regression analysis was used to evaluate the risk of stroke according to serum CXCL12 levels. Receiver operating characteristic (ROC) curve was used to evaluate the accuracy of serum CXCL12 in diagnosing stroke.From 306 screened patients, a total of 239 patients with first-ever AIS were included in this study. The results indicated that the serum CXCL12 levels were significantly higher in AIS patients as compared to normal controls (P 0.0001). Serum CXCL12 were positively correlated with infarct volume(r = 0.307, P 0.0001) and stroke severity(r = 0.288, P 0.0001). After adjusting for all other possible covariates, CXCL12 was a stroke predictor with an adjusted OR of 2.047 [95% confidence interval (CI), 1.781-2.352; P 0.0001]. Based on the ROC curve, the optimal cutoff value of serum CXCL12 levels as an indicator for auxiliary diagnosis of AIS was projected to be 3.4 ng/ml, which yielded a sensitivity of 87.9% and a specificity of 72.0%, with the area under the curve at 0.902 (95% CI, 0.875-0.929).Our study demonstrated that serum CXCL12 levels increased significantly following AIS, and these changes in serum CXCL12 were positively correlated with infarct volume and stroke severity in Chinese sample.

Expression of vesicular glutamate transporters (VGLUTs: VGLUT1, VGLUT2 and VGLUT3) in muscle spindle afferents was examined in rats. VGLUT1 immunoreactivity was detected in the sensory endings on the equatorial and juxta-equatarial regions of intrafusal fibers as well as in many axon terminals within lamina IX of the spinal cord. VGLUT1 might be expressed not only in the central axon terminals but also in the peripheral sensory endings of muscle-spindle afferents.

Protein kinase C gamma isoform (PKCgamma) is present at high levels in the spinal and medullary dorsal horns and is thought to play a role in the sensitization of dorsal horn neurons in certain pain states. Calbindin-D28k (CB), calretinin (CR) and parvalbumin (PV) are the most commonly expressed calcium-binding proteins and are located abundantly in the medullary dorsal horn (also called the caudal subnucleus of the spinal trigeminal nucleus). In the present study, immunofluorescence histochemical double staining for PKCgamma and CB, CR or PV was performed in the rat medullary dorsal horn. Most of the PKCgamma-, CB-, CR- and PV-immunoreactive neurons were observed in lamina II; some were also encountered in lamina I and lamina III of the medullary dorsal horn. Neurons co-expressing CB/PKCgamma, CR/PKCgamma and PV/PKCgamma were also mainly found in lamina II, while in lamina I and lamina III, only a few neurons co-expressing CB/PKCgamma, CR/PKCgamma and PV/PKCgamma were encountered. The percentages of neurons co-expressing CB/PKCgamma in the total numbers of CB- and PKCgamma-immunoreactive neurons were 6.7 and 5.9%, respectively. Of the total numbers of CR- and PKCgamma-immunoreactive neurons, 5.0 and 5.6%, respectively, showed both CR and PKCgamma immunoreactivities. The percentages of neurons co-expressing PV/PKCgamma in the total numbers of PV- and PKCgamma-immunoreactive neurons were 25.7 and 4.1%, respectively. Most of these neurons co-expressing CB/PKCgamma, CR/PKCgamma and PV/PKCgamma were small (/=15 microm) and medium-sized (16-35 microm) neurons and had round, triangular or fusiform-shaped cell bodies; large (/=36 microm) multipolar neurons were infrequently seen. The present results indicate that there are some neurons co-expressing CB/PKCgamma, CR/PKCgamma and PV/PKCgamma in the medullary dorsal horn. These neurons might play important roles in the nociceptive modulation from the oro-facial region.

By using the reverse transcriptase polymerase chain reaction technique, the expression of 5-hydroxytryptamine (5-HT) receptor subtype mRNAs in the rat lumbar dorsal root ganglion (DRG) was investigated following unilateral injection of complete Freund's adjuvant (CFA) into the rat hind paw. The results showed that 5-HT 1A , 5-HT 1B , 5-HT 1D , 5-HT 1F , 5-HT 2A , 5-HT 3 , 5-HT 4 , 5-HT 5A and 5-HT 7 receptor subtypes were present in the rat lumbar DRG. CFA injection resulted in a significant increase in mRNA level of 5-HT 1A , 5-HT 1B , 5-HT 1F , 5-HT 2A , 5-HT 3 , 5-HT 4 and 5-HT 7 receptor subtypes and a marked induction of 5-HT 2C subtype mRNA in the DRG. The present results suggest the important roles for these 5-HT receptor subtypes in generating peripheral nociceptive signaling and provide evidence to elucidate the mechanism of 5-HT in nociception.

Our previous work has shown that preconditioning can promote the recovery of cardiac function in patients having an open heart procedure. Because preconditioning is regarded as the most powerful form of endogenous myocardial protection, we tested the hypothesis that preconditioning protects against myocardial ischemia-reperfusion injury in patients undergoing prolonged cold crystalloid cardioplegic arrest.Thirty patients who had rheumatic heart disease and required both aortic and mitral valve replacement were studied. Patients were randomly divided into two equal groups. Preconditioning was accomplished using two cycles of 2-minute occlusion of the vena cava and aorta followed by 3 minutes of reperfusion under cardiopulmonary bypass. All hearts were arrested with 4 degrees C St. Thomas' Hospital cardioplegic solution. Myocardial protective effects were assessed by changes in myocardial levels of adenosine triphosphate, electrocardiographic activity, leakage of myocardial enzymes, and myocardial contractility.The adenosine triphosphate content in ischemic myocardium was higher in the preconditioning group than in the control group (p0.05 90 minutes after ischemia), and there was a significant reduction in release of the myocardial-specific isoenzyme of creatine kinase in the preconditioning group. Preconditioning improved the recovery of myocardial contractility (first derivative of left ventricular developed pressure, 1,490 +/- 102 mm Hg/s versus 1,250 +/- 97 mm Hg/s 30 minutes after reperfusion; p0.05), and there was also a protective effect on electrocardiographic activity.Our results suggest that ischemic preconditioning protects the myocardium in humans from the severe ischemia-reperfusion injury produced after prolonged arrest with cold crystalloid cardioplegia.

To investigate the correlation between blood flow assessed by CT perfusion imaging and characteristics of microvascular ultrastructure in non-small cell lung cancer (NSCLC).twenty-eight patients with non-small cell lung cancer proven surgically and pathologically underwent perfusion CT examination. The patients were divided into a hyper-perfusion group and a hypo-perfusion group by the median value of blood flow, and then the differences of microvascular ultrastructure in the two groups were analyzed.The median BF value of the 28 patients was 36.40 ml×100 g(-1)×min(-1). Take this median value as the boundary, the group with hypo-perfusion showed a significantly lower BF value than the group with hyper-perfusion [(30.84 ± 4.79) ml×100 g(-1)×min(-1) vs. (49.67 ± 10.89) ml×100 g(-1)×min(-1), t = -5.925, P0.001]. The group with lymph node metastasis showed a significantly lower BF value than the group without lymph node metastasis [(30.78 ± 5.24) ml×100 g(-1)×min(-1) vs. (50.73 ± 11.16) ml×100 g(-1)×min(-1), t = 3.490, P = 0.015]. The maturity of microvessels of the hyper-perfusion group was higher than that of the hypo-perfusion group. Under the electron microscope, the microvessels in the hypo-perfusion group showed a more narrow lumen, poorer integrity of basement membrane, a more close relationship between cancer cells and microvascular wall, and cancer cells were more easily seen in the microvascular lumen.The blood flow value of CT perfusion imaging may be related with the abnormal microvascular ultrastructure, and may be helpful to the prediction of metastasis risk in NSCLC.

Data on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.The survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP140/90 mmHg and130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.The analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to140/90 mmHg and130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P0.001). When the threshold of BP130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P0.05). Using the threshold of140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P0.05).The prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Our recent work has shown that calcitonin gene-related peptide (CGRP) may play an important role in mediation of ischemic preconditioning. Therefore, we tested the hypothesis that CGRP-induced preconditioning protects against myocardial damage after prolonged cardioplegic arrest in isolated rat hearts.Six groups were studied: the control, ischemic preconditioning, and CGRP-pretreated groups for both 4- and 8-hour hypothermic ischemia. All hearts were arrested using St. Thomas Hospital cardioplegia, and then reperfused with normothermic Krebs-Henseleit solution for 60 minutes after the 4- or 8-hour hypothermic ischemic period. Hearts were subjected to two cycles of 5-minute ischemia and 10-minute reperfusion in the ischemic preconditioning group. In the CGRP-pretreated group, Krebs-Henseleit solution containing CGRP (5 x 10(-9) mol/L) was substituted for the ischemic period.At 30 minutes of reperfusion after 4-hour storage, left ventricular pressure (mm Hg) and its first derivative (dp/dtmax, mm Hg/s) in the control, ischemic preconditioning, and CGRP groups were 65.2 +/- 5.93 and 1,170 +/- 119, 94.13 +/- 4.93 and 1,825 +/- 145.83, and 85.47 +/- 4.17 and 1,900 +/- 123.13, respectively (p0.01). After 8-hour storage, left ventricular pressure (mm Hg) and dp/dtmax (mm Hg/s) in the same groups were 51.07 +/- 5.83 and 815 +/- 107.17, 83.47 +/- 6.54 and 1,480 +/- 120.91, and 84.8 +/- 8.49 and 1,396 +/- 126.16 (p0.01). Ischemic preconditioning and CGRP-induced preconditioning also significantly reduced the release of myocardial enzymes.The present studies suggest that ischemic preconditioning protects against ischemia-reperfusion injury even after 8 hours of hypothermic preservation in isolated rat hearts, and that CGRP exerts preconditioning-like cardioprotection.

Current treatments for neuropathic pain are far from satisfactory. Considering the essential contribution of central immune factors to the pathogenesis of neuropathic pain, targeting inflammatory response is well accepted as an effective strategy for treating neuropathic pain. Triptolide has a long history in traditional Chinese medicine for treating inflammatory diseases and has been proven to inhibit cytokines released from glial cells.In the present study, we tested whether systemic treatment with triptolide could prevent or attenuate nocifensive behaviors associated with neuropathic pain. We further tried to explore the underlying mechanism of the potential anti-allodynia effect of triptolide.A randomized, double blind, controlled animal trial.Triptolide was administered systemically in a rat model of neuropathic pain induced by spinal nerve ligation (SNL) in the single bolus and repeated treatment manners. In the single bolus treatment experiment, triptolide (30 ug/kg, 100 ug/kg, 300 ug/kg) or vehicle was given to SNL and sham-operated rats once on day 1 or on day 10 after surgery (n = 6 each). In the repeated treatment study, prophylactic treatment with triptolide (30 ug/kg, 100 ug/kg, 300 ug/kg) was given to rats during the period of day -3 (3 days prior to SNL) to day 7 (7 days post-SNL) inclusively (n = 6 each). Another set of SNL and sham rats on postoperative day 10 received treatment with triptolide (30 ug/kg, 100 ug/kg, 300 ug/kg) or vehicle during the period of days 11-20 inclusively (n = 6 each), to assess potential reversal of established pain behavior. Mechanical allodynia of the rats was tested with von Frey filaments. Astrocytic and microglial activation in the spinal dorsal horn was evaluated with immunofluorescent histochemistry. Phosphorylation of mitogen-activated protein kinases (MAPKs), and expression of inflammatory cytokines (interleukin-6, interleukin-1beta, monocyte chemotactic protein-1, and tumor necrosis factor-alpha) were examined with Western blot analysis and real-time reverse transcription polymerase chain reaction study.A single bolus treatment with triptolide could neither prevent the induction nor reverse the maintenance of SNL-induced mechanical allodynia. However, repeated administration of triptolide dose-dependently inhibited neuropathic pain behavior in both preventative and interventional paradigms. Triptolide hampered SNL-induced activation of glial cells (astrocytes and microglia) in the spinal dorsal horn without influencing neurons. In addition, SNL-induced phosphorylation of MAPKs could be inhibited by triptolide. Furthermore, up-regulated expression of inflammatory cytokines in neuropathic pain states could be remarkably blocked by triptolide.The direct target site (such as a specific receptor) of triptolide is still to be determined. In addition, triptolide could not completely block the SNL-induced mechanical allodynia.Our data suggest that triptolide may be a potential novel treatment for neuropathic pain through modulating immune response in the spinal dorsal horn.

Acrolein signaling is important during spinal cord injury; whether it is involved in somatic and emotional pain is not clear. Hydralazine is a potent antihypertensive drug and can scavenge acrolein efficiently.We hypothesized that hydralazine decreases spinal level acrolein and renders analgesic effects with some side effects, which was tested in the current study.Subcutaneous injection of formalin was used to induce somatic and emotional pain responses. The spinal neuronal activation (FOS expression) and acrolein expression were evaluated at 2 hours after subcutaneous formalin injection. The possible side effects of hydralazine on the murine central nervous system or cardiovascular system were evaluated at one hour after hydralazine injection with open field, elevated plus maze and rotarod tests, or telemetrical measurement of mean artery blood pressure and heart rate.The subcutanous injection of formalin into the left hind paw induced significant somatic and emotional pain responses, evaluated by the biphasic spontaneous flinch/licking of the injected hind paw and interphase ultrasonic vocalizations during the one hour window after formalin injection. The spinal acrolein level was significantly increased and neurons were activated at 2 hours after formalin injection. Intraperitoneal injection of hydralazine (at 0.1, 1 or 10 mg/kg of body weight) at one hour before formalin challenging dose-dependently attenuated the formalin induced pain responses with an analgesic 50% effect dose ranging from 0.2 to 1 mg/kg of body weight. Furthermore, the neuronal activation and elevated acrolein expression were dose-dependently inhibited by hydralazine pretreatment. The side effects of intraperitoneal hydralazine on locomotion, anxiety, and motor coordination at one hour after hydralazine administration had negative results. The main side effects of hydralazine were an insignificant decrease of blood pressure and a significant increase of heart rates at high dose (10 mg/kg of body weight).This study is limited because the analgesic effect of hydralazine was tested on only one type of acute inflammatory pain model; however, its effect on chronic inflammatory or neuropathic pain needs to be further investigated.Based on the above findings, hydralazine may find its new application of analgesia within a safe dose window (around one mg/kg of body weight) without causing severe side effects.

The present study was designed to test the hypothesis that a medium-term simulated microgravity can induce region-specific remodeling in large elastic arteries with their innermost smooth muscle (SM) layers being most profoundly affected. The second purpose was to examine whether these changes can be prevented by a simulated intermittent artificial gravity (IAG). The third purpose was to elucidate whether vascular local renin-angiotensin system (L-RAS) plays an important role in the regional vascular remodeling and its prevention by the gravity-based countermeasure. This study consisted of two interconnected series of in-vivo and ex-vivo experiments. In the in-vivo experiments, the tail-suspended, hindlimb unloaded rat model was used to simulate microgravity-induced cardiovascular deconditioning for 28 days (SUS group); and during the simulation period, another group was subjected to daily 1-hour dorso-ventral (-G(x)) gravitation provided by restoring to normal standing posture (S + D group). The activity of vascular L-RAS was evaluated by examining the gene and protein expression of angiotensinogen (Ao) and angiotensin II receptor type 1 (AT1R) in the arterial wall tissue. The results showed that SUS induced an increase in the media thickness of the common carotid artery due to hypertrophy of the four SM layers and a decrease in the total cross-sectional area of the nine SM layers of the abdominal aorta without significant change in its media thickness. And for both arteries, the most prominent changes were in the innermost SM layers. Immunohistochemistry and in situ hybridization revealed that SUS induced an up- and down-regulation of Ao and AT1R expression in the vessel wall of common carotid artery and abdominal aorta, respectively, which was further confirmed by Western blot analysis and real time PCR analysis. Daily 1-hour restoring to normal standing posture over 28 days fully prevented these remodeling and L-RAS changes in the large elastic arteries that might occur due to SUS alone. In the ex-vivo experiments, to elucidate the important role of transmural pressure in vascular regional remodeling and differential regulation of L-RAS activity, we established an organ culture system in which rat common carotid artery, held at in-vivo length, can be perfused and pressurized at varied flow and pressure for 7 days. In arteries perfused at a flow rate of 7.9 mL/min and pressurized at 150 mmHg, but not at 0 or 80 mmHg, for 3 days led to an augmentation of c-fibronectin (c-FN) expression, which was also more markedly expressed in the innermost SM layers, and an increase in Ang II production detected in the perfusion fluid. However, the enhanced c-FN expression and increased Ang II production that might occur due to a sustained high perfusion pressure alone were fully prevented by daily restoration to 0 or 80 mmHg for a short duration. These findings from in-vivo and ex-vivo experiments have provided evidence supporting our hypothesis that redistribution of transmural pressures might be the primary factor that initiates region-specific remodeling of arteries during microgravity and the mechanism of IAG is associated with an intermittent restoration of the transmural pressures to their normal distribution. And they also provide support to the hypothesis that L-RAS plays an important role in vascular adaptation to microgravity and its prevention by the IAG countermeasure.

To investigate the type and frequency of gene conversion from SMN1 to SMN2 in Chinese patients affected with spinal muscular atrophy (SMA), and to explore the relationship between gene conversion and clinical phenotype.Non-homozygous deletion of SMN1 gene exon 8 was screened among 417 patients with SMN1 exon 7 homozygous deletions. To analyze and verify the types of gene conversion, genomic DNA sequencing, multiplex ligation-dependent probe amplification (MLPA), and gene subcloning and sequencing were carried out.Thirty-one patients (7.4% of all) with non-homozygous deletions of SMN1 exon 8 were detected. Through series of experiments, the fusion genes SMN1/SMN2 in all cases were delineated. Five types of gene conversions were identified, which included SMN2-I7b/SMN1 E8, SMN2-I7a/SMN1 I7b, SMN2-E7/SMN1 I7a, SMN1 I6/SMN2 E7/SMN1 I7a and SMN2-E7/SMN1 I7a/SMN2 I7b. Such conversions were found in the type I-III patients. For 10 patients with type I-III SMA and 3 copies of SMN2 gene produced by conversion, the average survival age was 5 year and 4 months.Partial conversions of SMN1 gene have been found among Chinese SMA patients. The type of conversion and frequency seem to be different from those of other races. Gene conversion to some extent may impact on survival time and rate of SMA patients, especially type I SMA.

To study the effects of yi-zhi II (a compond of Chinese Traditional Medicine) on the alteration of synaptic structure in hippocampal CA3 and maintenance of memoy.By using the method of oral administration of yi-zhi II, the step-through test and electron microscopy, the latency of step-through and synaptic structure in hippocamal CA3 were tested.(1) The mice which had been given yi-zhi II prolong significantly the latency of step through (P0.05 or P0.01) on the 1st, 6th and 12th day after learning. (2) On the 6th and 12th day after learning, the length of synaptic active zone were markly improved in yi-zhi II and control, but that of yi-zhi II was better than that of control. (On the 6th day after learning, the number of perforated synapses and axo-dendrite synapses were significantly improved by the yi-zhi II (P0.05).The yi-zhi II could improve the learning and memory in mice. It migth improve the memory by increasing the length of synaptic active zone and the number of perforated synapses and axo-dendrite synapses in hippocampal CA3.

To observe the therapeutic effect of acupuncture for treatment of patients with nonalcoholic steatohepatitis.Ninety-eight cases were randomly divided into an acupuncture group (n= 50) and a medicine group (n=48). The acupuncture group was treated with acupuncture at Shenshu (BL 23), Guanyuan (CV 4), Taixi (KI 3), Sanyinjiao (SP 6), etc.; the medicine group was treated with oral administration of Polyene Phosphatidylcholine Capsules. They were treated for 12 weeks. The changes of clinical symptoms, serum enzyme, blood fat and abdominal CT performance were compared between the two groups before and after treatment.After treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), galactosylhydroxylysyl glucosyltransferase (GGT), triglyeride (TG) and total cholesterol (TC) significantly decreased in the acupuncture group (all P0.01); ALT, AST and GGT significantly decreased in the medicine group (all P0.01), and there were no significant differences in changes of TG and TC in the medicine group (both P0.05). After treatment, CT image showed there was significant improvement of liver injury in both groups (both P0.01), and the improvement of liver injury in the acupuncture group was superior to that in the medicine group (P0.01).Acupuncture has a significant therapeutic effect on nonalcoholic steatohepatitis.

Tobacco smoking is the main risk factor associated with chronic periodontitis, but the mechanisms that underlie this relationship are largely unknown. Recent reports proposed that nicotine plays an important role in tobacco-related morbidity by acting through the nicotinic acetylcholine receptors (nAChRs) expressed by non-neuronal cells. The aim of this study was to investigate whether alpha 7 nAChR was expressed in periodontal tissues and whether it functions by regulating IL-1 beta in the process of periodontitis. In vitro, human periodontal ligament (PDL) cells were cultured with 10(-12) M of nicotine and/or 10(-9) M of alpha-bungarotoxin (alpha-Btx), a alpha 7 nAChR antagonist. The expression of alpha 7 nAChR and IL-1 beta in PDL cells and the effects of nicotine/alpha-Btx administration on their expression were explored. In vivo, an experimental periodontitis rat model was established, and the effects of nicotine/alpha-Btx administration on expression of alpha 7 nAChR and development of periodontitis were evaluated. We found that alpha 7 nAChR was present in human PDL cells and rat periodontal tissues. The expressions of alpha 7 nAChR and IL-1 beta were significantly increased by nicotine administration, whereas alpha-Btx treatment partially suppressed these effects. This study was the first to demonstrate the functional expression of alpha 7 nAChR in human PDL cells and rat periodontal tissues. Our results may be pertinent to a better understanding of the relationships among smoking, nicotine, and periodontitis.

To study the proliferation of Toxoplasma gondii RH strain tachyzoites in human foreskin fibroblast (HFF) cells and HeLa cells.HFF cells and HeLa cells were cultured in 35 mm cell culture dishes with glass cover slip. Confluent cells were co-cultured with tachyzoites which purified by 3 microm filter membrane. At 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, and 96 h after co-culture, the invasion of tachyzoites into the cells and proliferation in cells were observed with Giemsa staining.In 4 h after co-culture, there were dozens of T. gondii tachyzoites in the HFF cells. At 24 h many pseudocysts emerged. At 72 h most of the cells were destroyed by tachyzoites. While cultured in HeLa cells for 8 h, there were only 3-5 tachyzoites in one cell, and pseudocysts emerged at 48 h. At 96 h after co-culture, most cells were destroyed.Toxoplasma gondii tachyzoites can be cultured in HFF cells and HeLa cells. The proliferation of tachyzoites in HFF cells was quicker than that in HeLa cells.

To investigate clinical and pathological characteristics of lung mucoepidermoid tumors and summarize methods for diagnosing and treating it.Records of a total of 2,751 consecutive patients with lung cancer were reviewed and 10 of whom with mucoepidermoid tumors were identified. Chest radiographs, computer tomographs, and bronchoscopes were performed to all of them. Eight of them underwent thoracotomy and some also received chemotherapy and/or radiotherapy. One patient received Chinese herb therapy only while another did not receive any therapy.Pathological examination showed that the 10 patients had low-grade mucoepidermoid tumors. All patients were alive. Seven patients who received thoracotomy did not recur. One patient whose tumor was located in trachea recurred 5.2 years after the operation.Bronchoscope can play an important role in the process of diagnosis. Pathological staging is vital for prognosis. Lung mucoepidermoid tumors should be treated with complete surgical resection with lymph node sampling and dissection and close follow-up.

To investigate the effect of HOE642 on cardiac myocyte apoptosis of the heterotopic heart transplantation of rat non heart-beating donors.Totally 112 male Sprague-Dawley rats were randomly divided into 7 groups (n=16 in each group) C, the control group (normal hearts); S10, S30, and S45 (groups of transplanted hearts after 10, 30, and 45 minutes of asystole); and SH10, SH30, and SH45 (groups of transplanted hearts after 10, 30, and 45 minutes of asystole and infused with HOE642). After rata in the experimental groups were killed by warm ischemia the donators of the S10, S30 and S45 groups were infused with 5TH-1 for 30 minutes, and the dead rats in group SH10, SH30, and SH4 were infused with STH-1 and HOE642 (20 micromol/L) for 30 minutes. Heterotopic heart transplantation were processed by the method of neck Cuff. The heart specimens of S10, SH10, S30, and SH30 groups were taken after 48 hours of transplantation, and the heart specimens of S45 and SH45 groups were taken immediately after transplantation. Then apoptotic myocytes were detected with terminal deoxynucleotide transferase-mediated deoxyuridine-biotin nick end labeling method and the expressions of Bcl-2, Bax, and Caspase-3 proteins were detected by immunohistochemistry.The rats were discerned death when cardiac electric wave vanished after 9-11 minutes of bloodletting by transsection of abdominal aorta. The number of positive cardiac muscle cells in S10 and S30 groups were significantly larger than those in group SH10 and SH30 (P0.05). The levels of Bcl-2 protein expression in S10 and S30 groups were significantly lower than those in SH10 and SH30 groups (P0.05). The levels of Bax and Caspase-3 protein expression were significantly higher than those in SH10 and SH30 groups (P0.05).The rat model of a heterotopic heart transplantation on the cervical part is a convenient animal model for cardiac muscle protection. HOE642 can suppress rat cardiac muscle cells apoptosis (within 30 min) after death caused by warm ischemia.

To detect the expression of bcl-2 and bax genes after heterotopic heart transplantation in rats that died of warm ischemia, and to explore the effect of cariporide on the protection of the ratos non heart-beating donors.One hundred and twelve clearing Sprague-Dawley male rats were divided into 7 groups at random (each group contained 16 rats): the control group (Group C), the groups of transplanted hearts after 10, 30, and 45 min of asystolia (Group S10,S30,and S45), and the groups of transplanted hearts after 10,30, and 45 min of asystolia and infused with cariporide(Group SH10,SH30, and SH45).The experimental groups were sacrificed totally by warm ischemia, and heterotopic heart transplantation was processed by the Cuff method. The heart samples of S10,SH10,S30, and SH30 groups were taken at 48 hours after the transplantation, and the heart samples of S45, and SH45 groups were taken just after transplantation. The expression of bcl-2 and bax genes were detected by RT-PCR.The death of rats was affirmed when cardiac electric waves vanished after 9~11 minutes of transsection of abdominal aorta. On the RT-PCR test, the expression of bcl-2 gene was the highest and ROD value was maximum in the control group. The expression of bax gene was the lowest and ROD value was minimum in the control group. The ROD value of bcl-2 genes in S10 and S30 groups was less than that in SH10 and SH30 group. The ROD value was just the opposite, and there was stastistical difference (P0.05).There was no statistical difference between Group S45 and Group SH45 (P0.05).The model of heteroto-pic neck heart transplantation is a convenient animal model for the cardiac muscle protection. Cariporide can suppress the apoptosis of cardiac muscle cells in rats (within 30 min) after death caused by warm ischemia.

To investigate the methods to alleviate lung injury of non-heart-beating donor to attain better structure and function.Sixty-four Sprague-Dawley rats were randomly divided into 4 groupsú a heart-beating donor group(HBD group), a non-heart-beating donor group without protective measures(NHBD-N group), a non-heart-beating donor group with continuous mechanical ventilation or with topical cooling on cadaver lung (NHBD-V group and NHBD-I group). After the transplantation, lung compliance,pulmonary function,wet/dry ratio of lung and content of energy metabolism were compared among the 4 groups.Due to the longer warm ischemic period, NHBD lungs suffered more injuries than HBD lungs. However, compared with NHBD-N group, the wet/dry ratio of the lung in NHBD-V group and NHBD-I group was lower(5.28+/-1.24,4.21+/-0.85,4.14+/-1.33,P0.01),the lung injury index (14.35+/-3.21,11.28+/-3.26,10.41+/-2.85, P0.01)and the count of white blood cells(425.60+/-86.47,316.30+/-56.24,295.50+/-70.26, P0.01) were milder, while the lung compliance and preservation of energetic metabolte were better in the NHBD-V group and the NHBD-I group.Continuous mechanical ventilation or topical cooling may protect the NHBD lung during the warm ischemic period.

To summarize 210 cases of lung cancer that underwent pneumonectomy,and to study the therapy value of pneumonectomy for lung cancer.Between January 1993 and December 2004,210 patients (169 males and 41 females) with lung cancer underwent pneumonectomy in our hospital with the mean age of 54.77 years. Out of the 210 cases 144 had left pneumonectomy, and 66 had right pneumonectomy. Among them, 26 experienced intrapericardial pneumonectomy,1 inferior vena cava reconstruction, and 1 carina reconstruction. All bronchial stumps were closed by manual suture,and systemic node dissection was performed routinely.No one died during the operation, but 59 patients (28.10%) experienced postoperative complications and 9 patients (4.28%) died within 30 days of operation. After exclusion of postoperative deaths, the 1-year, 3-year, and 5-year survival rates were 66.21%,36.13% and 24.26%, respectively. Only 1 out of the 12 patients with small cell carcinoma survived more than 3 years.Mortality and morbidity were high in pneumonectomy.If we carefully and properly select the patients, enhance postoperative monitoring and perioperative treatment, and combine with chemo-and/or radiotherapy,pneumonectomy will surely be effective for patients with lung cancer.

To summarize the experience of mitral vavuloplasty for mitral insufficiency in 53 patients.Between January 2001 and September 2006,53 patients (31 males and 22 females) with mitral insufficiency underwent mitral valve repair at our hospital. The mean age was (23.8+/-10.4) years, and the mean weight was (43+/-12) kg,including 29 cases of mitral prolapse,17 congenital mitral insufficiency, 5 rheumatic mitral insufficiency,and 2 other etiology. All operations were performed under cardiopulmonary bypass,moderate hypothermia and under the surveillance of transesophagus echocardiography.There were 2 early postoperative deaths,and another patient failed to repair and received valve replacement afterward. Postoperative echocardiography indicated that mitral insufficiency was completely corrected in 42 patients, and residual mitral regurginitation in the other 8 patients. During the follow-up with mean period 13.8 months,41 patients revealed 28 in NYHA classI,13 in Class II.Mitral valve repair should be the preferred modes of surgical correction for regurgitate mitral valves. With proper vavuloplasty technique, patients with selective mitral insufficiency patients may achieve satisfactory effect.

To determine the surgical point and technique of artificial mechanical valve replacement in children with heart valve diseases.From Jan. 1989 to Oct. 2005, 63 children under 15 years received mechanical cardiac valve replacement with cardiopulmonary bypass (CPB).The valve replacement included aortic valve replacement in 20 children, mitral valve replacement in 37 children and combined aortic valve and mitral valve replacement in 6 children.The operation mortality was 7.94%(5/63). The follow-up periods were from 4 months to 204 months. The late mortality was 10.34%(6/58). All the other children were in NYHA class I - II. The operation mortality of children with heart valve replacement is higher than that of adults, but it was very effective.

To summarize the method and experience of direct observation of the effect of mitral valvuloplasty on beating heart.Twelve patients with mitral regurgitation underwent mitral valvuloplasty. When the heart was beating slowly before releasing the aorta, the morphology and function of the mitral valve were evaluated by direct observation. If the results were unsatisfactory, further techniques were used to reach the goal.During the operation 2 patients needed further techniques to make the mitral valve work well. No operative death and only 1 complication (low cardiac output syndrome) occurred. After 1 month follow-up later, mild regurgitation was found in 5 patients, moderate regurgitation in 1 and no obvious regurgitation in 6.Evaluating the effect of mitral valvuloplasty by direct observation on beating heart is practicable.

To review the clinical data of pathological morphology, diagnosis, surgical treatment of cor triatriatum in 15 patients.Fifteen patients with a mean age of (14.6+/-10.3) years (range from 6 months to 40 years) were performed operations under extracorporeal circulation. Fourteen of the patients had cor triatriatum sinister, and 1 had cor triatriatum dexter; 12 of the 15 patients had other cardiac abnormalities. The excision of the fibromuscular membrane was accomplished through a right atrial incision in all of the 14 cases, and the associated abnormalities were corrected at the same time.One patient died after the operation, and the other survivors had good outcome.Operation is necessary if the diagnosis is clear. The patients generally have good prognosis. Surgical results of cor triatriatum depend on the complexity of associated defects and the adequacy of the repair.

Secreted proteins from cancer cells may be potential serologic biomarkers of cancer. It's important to globally identify secreted proteins of cancer cells. This study was to identify secreted proteins of lung cancer cells.Proteins in the conditioned medium of non-small cell lung cancer (NSCLC) cell line A549 was collected and the proteome analysis was subsequently performed. Specific protein spots in A549 cells were identified by peptide mass fingerprints using mass spectrometry and through searching database. The expression of identified secreted proteins was detected by reverse transcription-polymerase chain reaction (RT-PCR) in 15 specimens of NSCLC tissue and paired distant lung tissue. Manganese superoxide dismutase (Mn-SOD) activity in serum and conditioned medium was detected by spectrophotometry.Fourteen secreted proteins were identified, which included peptidyl-prolyl cis-trans isomerase A (PPIA), Mn-SOD, peroxiredoxin 1 (PDX1), phosphatidylethanolamine binding protein (PEBP), glutathione S-transferase P (GSTP1-1), glucose-dependent insulinotropic protein receptor (GIPR), ubiquitin carboxyl-terminal hydrolase isozyme L1 (PGP9.5), alpha enolase (ENO1), dihydrodiol dehydrogenase (DDH), phosphoglycerate mutase 1 (PGAM1), galectin-1 (GAL1). PPIA, DDH, PGAM1, PDX1, PGP9.5, ENO1, and PEBP were overexpressed in cancer tissues. Higher level of Mn-SOD activity was detected in conditioned medium than in control. Serum Mn-SOD activity was significantly higher in NSCLC patients than in healthy controls (P0.01).Multiple secreted proteins of A549 cells were identified in this study and the overexpression of ENO1 and PEBP in NSCLC was revealed for the first time. Mn-SOD is secreted serologic marker of NSCLC. The results presented here would provide clues to identify new serologic biomarkers of NSCLC.

To determine the effects of reacting cortisol on ischemic preconditioning (IPC).Thirty rabbits were randomized into ischemic preconditioning (IPC) group, etomidate (Etom) group, ischemic/reperfusion (IR) group, methylprednisolone (MP) group and a control group. The ratios of infarction size versus risk area (Infarct/Risk) were calculated. The elevations of serum CK activity and cTnI concentrations as well as serum cortisol concentrations were measured.The ratios of Infarct/Risk were 5.9%+/-2.8% for IPC, 11.3%+/-3.6% for Etom, 26.8%+/-4.5% for IR and 18.2%+/-3.7% for MP. The elevations of serum CK activity (U/L) were 255+/-89 for IPC, 314+/-160 for Etom, 855+/-371 for IR and 768+/-404 for MP, the elevations of serum cTnI concentrations (microg/L) were 3.6+/-0.6 for IPC, 5.9+/-2.0 for Etom, 8.1+/-3.6 for IR and 6.1+/-2.3 for MP. Those indicators among groups are all significantly different (P0.01). Cortisol reacting was markedly diminished in Etom group.A blunted cortisol reaction can markedly undermine the benefit of ischemic preconditioning, methylprednisolone show a certain myocardial protection. Cortisol may play an important role in the IPC process.

To determine the protective mechanism of preconditioning to the lung injury induced by ischemia-reperfusion.Twelve pigs were randomly divided into 2 groups: control group ( Group C) and ischemic preconditioning group ( Group IP). The concentration of superoxide distrautase (SOD) and malondialdehyde (MDA) in circuit were checked before and after the perfusion to reflect the lipid peroxidation in the lungs. Left lung biopsies were performed immediately after the perfusion and 1 hour postperfusion for histologic examination. The ICAM-1 expression was assessed by immunohistochemical analysis with Envision method and the mRNA expression of ICAM-1 was analyzed by RT-PCR.SOD in Group IP was much higher than that in Group C (P0.01 ). MDA in Group IP was much lower than that in Group C ( P0.01 ). The lung histologic examination showed that Group C was significantly more serious than Group IP in pulmonary edema, inflammatory cell infiltration, mild focal hemorrhage, and alveolar disruption. The expression of ICAM-1 of lung tissue obviously decreased in Group IP than that in Group C (P0.01 ). The expression of ICAM-1 mRNA of lung tissue was significantly lower in Group IP than that in Group C (P0.01 ).Lung ischemic preconditioning can reduce the lung injury. The mechanisms of the protective effects of the IP may be related to the increase of SOD and the decrease of MDA. The preconditioning down-regulated the ICAM-1 expression is one of the mechanisms in reducing the lung injury.

To evaluate the surgical technique and the effect of preservation of the entire mitral subvalvular apparatus during mitral valve replacement (MVR) in patients with mitral stenosis.MVR was performed on 56 patients with mitral stenosis. Of them, 11 had complete preservation of the entire mitral subvalvular apparatus (group A) with the technique of preservation of 'button-shaped' transplantation, 25 had the preservation of the posterior leaflet only (group B), and the other 20 underwent the conventional MVR (group C). Pre- and postoperative hemodynamic parameters were measured to determine the left ventricular performance. Echocardiography was performed preoperatively, at the time of discharge, and 3 to approximately 6 months postoperatively to determine the dimensions and ejection function.Cardiac index, stroke volume index and left ventricular stroke work index postoperatively in group A were better than those in group B and C (P0.05). Echocardiographic measurements postoperatively showed the increase of LVESD, LVEDD in group B and C, but a better LVL and LVFS in group A (P0.05), and LVEF was more pronounced in group A (P0.05). There appeared a long cross-clamp time in group A, but the total CPB time was not significant among the three groups.The surgical skills of preservation with 'button-shaped' transplantation may be a practical choice for patients with mitral stenosis. The preservation of entire mitral subvalvular apparatus improves the left ventricular functions after MVR in patients with mitral valve stenosis.

Immunofluorescence histochemical double-staining for preproenkephalin (PPE) and calbindin-D28k (CB), calretinin (CR) or parvalbumin (PV) were performed in the spinal trigeminal nucleus caudalis (Vc) of the rat. Neuronal cell bodies exhibiting PPE-like immunoreactivity were present in all laminae of the Vc, with a higher concentration in lamina II. Most of the CB-, CR- and PV-like immunoreactive neurons were located in lamina II, and some of them were also found in laminae I and III of the Vc. Some PPE-like immunoreactive neurons also showed CB-, CR-, or PV-like immunoreactivities. CB/PPE, CR/PPE and PV/PPE double-labelled neurons were mainly observed in lamina II. The percentages of CB/PPE double-labelled neurons in the total numbers of the CB- and PPE-like immunoreactive neurons were 3.5-1.5% and 3.3-15.7%, respectively. Of all CR- and PPE-like immunoreactive neurons, 4.7-13.5% and 3.7-14.2% showed both CR- and PPE-like immunoreactivities. The ratios of PV/PPE double-labelled neurons in all PV- and PPE-like immunoreactive neurons were 9.7-28.1% and 2.1-8.7%, respectively. The present results indicate that some enkephalinergic neurons in the Vc of the rat also contain calcium-binding proteins.

To review the experience of surgical treatment and the diagnosis of 41 patients with congenital heart diseases complicated with infective endocarditis.Twenty-three males and 18 females (the mean age 22.6 years) were studied. Twenty-seven patients received bacterial cultivation of blood specimens, and the results of bacterial cultivation of 11 patients were positive. Thirty-four patients underwent cardiac operations after infection was almost controlled, and 7 patients underwent operations during the infective phase. In all the cases, the infected tissues were excised, congenital cardiac was treated, and valvular dysfunctions were corrected.The surgical treatment results were satisfactory. One patient (2.4%) died during hospitalization.In our hospital, the incidence rate of infective endocarditis complicated with congenital heart diseases increases; echocardiography is a valuable tool in diagnosis; blood culture may be negative after previous administration of antibiotics; aggressive surgical treatment should be adopted in patients with congenital heart defects complicated with infective endocarditis.

Double immunofluorescence histochemistry for calcium-binding proteins was performed in the caudal subnucleus of the rat spinal trigeminal nucleus; for calbindin D28k (CB) and calretinin (CR), for CB and parvalbumin (PV), and for CB and CR. CB-immunoreactive (-ir) neurons were seen 1.7 times more frequently than CR-ir neurons and 5.5 times more frequently than PV-ir neurons. About 70-90% of these neurons were distributed in substantia gelatinosa. Co-existence of CB and CR was indicated in 2.3% of CB-ir and 3.9% of CR-ir neurons. Co-existence of CB and PV was indicated in 1.0% of CB-ir and 5.5% of PV-ir neurons. Co-existence of CR and PV was indicated in 1.4% of CR-ir and 5.1% of PV-ir neurons. In these doubly immunostained neurons, 59.5-69.5% were observed in substantia gelatinosa, 5.9-17.8% in the marginal zone, and 12.7-31.0% in the magnocellular part.