The clinical value of neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) for predicting the occurrence and severity of pneumonia in patients with intracerebral hemorrhage.

Background: Inflammatory mechanisms play important roles in intracerebral hemorrhage (ICH) and have been linked to the development of stroke-associated pneumonia (SAP). The neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) are inflammatory indexes that influence systemic inflammatory responses after stroke. In this study, we aimed to compare the predictive value of the NLR, SII, SIRI and PLR for SAP in patients with ICH to determine their application potential in the early identification of the severity of pneumonia. Methods: Patients with ICH in four hospitals were prospectively enrolled. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. Data on the NLR, SII, SIRI and PLR were collected at admission, and the correlation between these factors and the clinical pulmonary infection score (CPIS) was assessed through Spearman's analysis. Results: A total of 320 patients were enrolled in this study, among whom 126 (39.4%) developed SAP. The results of the receiver operating characteristic (ROC) analysis revealed that the NLR had the best predictive value for SAP (AUC: 0.748, 95% CI: 0.695-0.801), and this outcome remained significant after adjusting for other confounders in multivariable analysis (RR=1.090, 95% CI: 1.029-1.155). Among the four indexes, Spearman's analysis showed that the NLR was the most highly correlated with the CPIS (r=0.537, 95% CI: 0.395-0.654). The NLR could effectively predict ICU admission (AUC: 0.732, 95% CI: 0.671-0.786), and this finding remained significant in the multivariable analysis (RR=1.049, 95% CI: 1.009-1.089, P=0.036). Nomograms were created to predict the probability of SAP occurrence and ICU admission. Furthermore, the NLR could predict a good outcome at discharge (AUC: 0.761, 95% CI: 0.707-0.8147). Conclusions: Among the four indexes, the NLR was the best predictor for SAP occurrence and a poor outcome at discharge in ICH patients. It can therefore be used for the early identification of severe SAP and to predict ICU admission.

[Effect of Chinese Drugs for Breaking Blood Expelling Stasis on Acute Cerebral Hemorrhage: a Prospective Randomized Double-blind Controlled Study].

OBJECTIVE: To study the safety of using Chinese drugs for breaking blood expelling stasis (CDBBES) in hypertension patients with intracerebral hemorrhage within 6 h, and to observe whether they would result in hematoma enlargement. METHODS: A prospective randomized double-blind controlled clinical study was employed. Totally 128 cerebral hemorrhage patients within 6 h were recruited from 8 research centers from October 2013 to March 2015, and finally 76 of them were included. These patients were assigned to 3 groups by simple random sampling, group A, B, and C. Patients in group A (26 cases) took whole CDBBES recipe (containing leeches and equivalent insects). Those in group B (25 cases) took CDBBES recipe (removing leech and gradfly). Those in group C (25 cases) took placebos. Medication lasted for 10 successive days. The hematoma enlargement rate within 24 h, the occurrence of adverse reactions and adverse events were observed. To guarantee the safety of this trial, an interim analysis of first level unblinding was used. RESULTS: The hematoma enlargement rate was 11. 5% (3/26) in group A, 16. 0% (4/25) in group B, and 20. 0% (5/25) in group C. There was no statistical difference in the hematoma enlargement rate among the 3 groups (X² =0. 823, P =0. 682). Adverse reactions and adverse events occurred in 7 cases, 1 patient with acute myocardial infarction, 1 with chest op- pression and palpitation, 2 with diarrhea in group A. No patient had adverse reaction or adverse event in group B. And diarrhea occurred in 3 patients of group C. CONCLUSION: The interim analysis of first level unblinding showed that hematoma enlargement within 6 h was not resulted from using CDBBES.

Leptomeningeal carcinomatosis as the initial manifestation of gastric adenocarcinoma: a case report.

Leptomeningeal involvement is usually reported as a secondary event in advanced gastric carcinoma. Leptomeningeal carcinomatosis (LMC), as the initial manifestation of asymptomatic gastric cancer, is exceedingly rare with only a few cases reported in recent years. The presenting neurologic symptoms include headache, vomiting and seizures and are usually clinically atypical. The diagnosis of LMC is made via identification of malignant cells that originate from epithelial cells in the cerebrospinal fluid by cytological examination and provides cues to track the primary tumor. Endoscopic examinations are crucial to confirm the presence of gastric cancer, and imaging studies, especially gadolinium-enhanced magnetic resonance imaging of the brain, are sometimes helpful in diagnosis. Thus far, there is no standard therapy for LMC, and despite all measures, the prognosis of the condition is extremely poor. Here, we report on the clinical features and diagnostic procedures for a patient with occult gastric cancer with Bormann type I macroscopic appearance and poor differentiation in pathology, who presented with LMC-induced neurological symptoms as the initial clinical manifestation. Additionally, we review the similar cases reported over the past years, making comparison among cases in order to provide more information for the future diagnosis.

ABCG2 gene amplification and expression in esophageal cancer cells with acquired adriamycin resistance.

Resistance to chemotherapeutic agents is the main reason for treatment failure in patients with cancer. The primary mechanism of multidrug resistance (MDR) is the overexpression of drug efflux transporters, including ATP­binding cassette transporter G2 (ABCG2). To the best of our knowledge, the MDR mechanisms of esophageal cancer have not been described. An adriamycin (ADM)-resistant subline, Eca109/ADM, was generated from the Eca109 esophageal cancer cell line by a stepwise selection in ADM from 0.002 to 0.02 ng/µl. The resulting subline, designated Eca109/ADM, revealed a 3.29-fold resistance against ADM compared with the Eca109 cell line. The ABCG2 gene expression in the Eca109/ADM cells was increased compared with that of the Eca109 cells. The cellular properties of the Eca109/ADM cells were detected by reverse transcription polymerase chain reaction (RT-PCR), flow cytometry and western blotting. The ABCG2 expression levels were detected by RT-PCR and flow cytometry, and the drug efflux effect was detected by flow cytometry. The present study detected the correlation between ABCG2 and the multidrug resistance of esophageal cancer. ABCG2 gene expression and the drug efflux effect of the Eca109/ADM cells were increased compared with those of the Eca109 cells. Collectively, the results of this study indicated that the overexpression of ABCG2 in the Eca109/ADM cells resulted in drug efflux, which may be responsible for the development of esophageal cancer MDR.

Reversal of multidrug resistance by the anti-malaria drug artesunate in the esophageal cancer Eca109/ABCG2 cell line.

The overexpression of ATP-binding cassette (ABC) transporters confers multidrug resistance (MDR) to tumor cells. ABCG2 is a member of the ABC superfamily. The present study aimed to investigate the correlation between ABCG2 expression and the MDR of esophageal cancer and to estimate the therapeutic benefit of downregulating ABCG2 expression and reversing chemoresistance in esophageal cells using artesunate (Art). The Eca109/ABCG2 cell line was established by transfecting the ABCG2 gene into Eca109 cells. The Eca109/ABCG2 esophageal cancer cells with ABCG2 gene overexpression were resistant to adriamycin (ADM), daunorubicin (DNR) and mitoxantrone (MIT), which indicated that ABCG2 may be associated with drug resistance in esophageal cancer. Art is a noteworthy antimalarial agent, particularly in severe and drug-resistant cancer cases, as Art is able to reverse drug resistance. In the present study, Art also exerted profound anticancer activity. The mechanism for the reversal of multidrug resistance by Art in esophageal carcinoma was analyzed using cellular experiments, but still remains largely unknown.

Combinatorial effects of naomai yihao capsules and vascular endothelial growth factor gene-transfected bone marrow mesenchymal stem cells on angiogenesis in cerebral ischemic tissues in rats.

OBJECTIVE: To investigate the combinatorial effects of Naomai Yihao (NMYH) Capsules and vascular endothelial growth factor (VEGF) gene-transfected bone marrow mesenchymal stem cells (BMSCs) on angiogenesis in cerebral ischemic tissues in rats and the mechanism. METHOD: BMSCs were isolated and cultured from bone marrow by an adherence method. Then, BMSCs were transfected with the eukaryotic expression plasmid pEGFP-VEGF165 by positive ionic liposome transfection. A rat model of middle cerebral artery occlusion (MCAO) was established. Rats were allocated to six groups: model, BMSC, VEGF gene-transfected BMSC transplantation (BMSC/VEGF), NMYH, combined NMYH and BMSC/VEGF (combined treatment group) and sham operation groups. The behavioral rating score (BRS) of rats and the expression of CD34 and VEGF in brain tissue were measured by immunohistochemistry on days 7, 14 and 21 after reperfusion. Angiogenesis was observed and evaluated with laser scanning confocal microscopy. RESULTS: The BRS of rats in NMYH, BMSC transplantation and combined treatment groups was significantly lower than that of the model group (P < 0.001), with no significant difference between NMYH and transplantation groups (P = 0.619). The expression of CD34 and VEGF in NMYH, transplantation and combined treatment groups increased (P < 0.001), with a significant difference between NMYH and transplantation groups (P < 0.001). The blood vessel area in NMYH, transplantation and combined treatment groups was significantly increased (P < 0.05), without a significant difference between NMYH and transplantation groups (P = 0.873). CONCLUSIONS: VEGF gene-transfected BMSCs improve angiogenesis in the cerebral ischemic area. NMYH Capsules promote angiogenesis in MCAO rats treated with BMSC transplantation, which show an improved BRS. The mechanism of angiogenesis may be related to up-regulation of VEGF expression.

[Effect of integrative medical therapy on the prognosis of patients suffering from yin syndrome type acute ischemic stroke].

OBJECTIVE: To observe the effect of integrative medical therapy on the prognosis of patients suffering from yin syndrome type acute ischemic stroke (YS-AIS). METHODS: A multi-center, prospective, random and parallel controlled clinical trial was carried on 606 patients of YS-AIS. Excepting the 15 patients being excluded and dropped out in the trial period, all patients were assigned to the treatment group (274 patients) treated with integrated medical protocol (i. e. Chinese medical therapy plus conventional Western medical treatment), and the control group (263 patients) treated with conventional Western medical treatment plus placebo. Patients' quality of life (QOL) and their disability level were assessed by scoring based on SS-QOL and modified Rankin scale (mRS) respectively at the terminal of the 21-day treatment (T1) and at the ends of 60-day (T2) and 90-day (T3) following-ups. RESULTS: Patients' disability level, showed by mRS scores, was not significantly different between the two groups at T1 and T2 (P > 0.05), but with significant difference at T3 (P < 0.05). The recovery in the treatment group were more significant. Although the SS-QOL scores showed no statistical significant difference between groups (P > 0.05), improvement of QOL could be seen in the treatment group and the difference between groups was more significant as the time went by. CONCLUSION: Integrative medical therapy could reduce the severe disability rate in patients after YS-AIS, and showed an improving trend on patients' QOL at T3.

Construction of mTNFR1shRNA plasmid and its biological effects on MHV-3 induced fulminant hepatitis in BALB/cJ mice.

Previous study on TNFR1-mediated hepatocyte apoptosis has been implicated in the development of fulminant viral hepatitis. To interfere with the potentially effective target, plasmid named p-mTNFR1shRNA complimentary to the sequence responsible for mTNFR1 was also constructed and further confirmed by sequence analysis. To investigate the effect of mTNFR1shRNA plasmid on mTNFR1 expression in vivo and the disease progress in MHV-3 induced fulminant hepatitis mice model. By hydrodynamic injection of mTNFR1shRNA plasmid, the survival rate of mice, hepatic pathological change were examined and compared between mice with/without mTNFR1shRNA plasmid intervention. The expression of mTNFR1 was detected by Real-time PCR, immunohistochemistry staining. The mTNFR1shRNA plasmid significantly reduced mTNFR1 expression in vivo, markedly ameliorates inflammatory infiltration, prolonged the survival time period and elevated the survival rate from 0 up to 13.3% in Balb/cJ mice with MHV-3 induced fulminant hepatitis. This study was designed to explore the opportunity of RNA interference technique in inhibiting TNFR1 expression, which has been reported to be involved in the development of a variety of diseases including fulminant viral hepatitis and severe chronic hepatitis B.

Outcome and safety assessment of an herbal medicine treatment protocol for yin pattern of acute ischemic stroke.

BACKGROUND: The morbidity of stroke is high. Traditional Chinese medicine is commonly used for patients with ischemic stroke in China, but the efficacy need be further proved. OBJECTIVE: To assess the efficacy and safety of an herbal medicine treatment regimen integrating traditional Chinese medicine and Western medicine for ischemic stroke patients with yin pattern syndrome. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A multicenter, randomized and controlled clinical trial was adopted. A total of 537 patients with acute ischemic stroke were enrolled in 22 hospitals from July 2005 to October 2006, among whom 274 were assigned to group A (herbal group) and administered with Western medicine plus herbal medicine treatment, and the other 263 in group B (control group) with Western medicine plus placebo. The patients in two groups were all treated for 21 days. MAIN OUTCOME MEASURES: The primary endpoint of outcome measures was Barthel index. The secondary endpoints included National Institutes of Health Stroke Scale, the modified Rankin criteria, Stroke Specific Quality of Life, and Stroke Scale of Traditional Chinese Medicine. The adverse effects of the treatment were also observed. RESULTS: A total of 622 randomization numbers were applied by the centers and 16 numbers were lost for mishandling, so a total of 606 patients were included. Fifteen patients were excluded (5 in group A, and 10 in group B), and 54 (25 in group A, and 29 in group B) lost in follow-up. A total of 537 patients completed the trial and a per-protocol set analysis was conducted. There were no statistical differences in age, sex, pulse rate, heart rate, respiratory rate, blood pressure, medical history, neurological deficit scores, scores on Glasgow Coma Scale, and lesion size of intracerebral ischemia between the two groups at baseline (P>0.05). Twelve patients, including 5 in group A and 7 in group B, died during the 90 days of research period, and no significant difference was found between the two groups. Compared with Western medicine alone, herbal medicine treatment could improve the neurological deficit at day 21, activities of daily living at day 90 of follow-up, and the patient-reported outcome at days 21, 60, and 90 (P<0.05). Independent living ability of the patients was also improved (67.9% of group A vs 59.3% of group B, 0-1 at modified Rankin criteria). Moreover, the herbal medicine treatment showed a tendency in improving quality of life at a time-dependent manner. Adverse events, including gastrointestinal adverse events, skin symptoms, hemorrhagic tendency, and aminotransferase increase, happened in 76 cases from both groups, and no significant difference was found between the two groups. Correlation analysis showed that aminotransferase increase was not related to the herbal medicine treatment, but to the lipid-lowering drugs. CONCLUSION: The present research demonstrates that the herbal medicine treatment shows effects on neurological deficit and patient-reported outcome at day 21, activities of daily living and handicap at day 60, and handicap, activities of daily living and patient-reported outcome at 3-month follow-up. TRIAL REGISTRATION NUMBER: NCT000351806

[Establishment of pig acute liver failure model and the role of pig fibrinogen-like protein 2].

OBJECTIVE: To establish a pig model of fulminant hepatic failure for evaluating the pre-clinical efficacy of drug treatment on severe hepatitis, and to detect the expression of fibrinogen-like protein-2 (fgl2) prothrombinase in the model, so as to provide basis for gene therapy targeting to fgl2 for fulminant hepatic failure. METHOD: D-galactosamine hydrochloride was used to induce pig model of fulminant hepatic failure, and the experiment animals were divided into model group (rapid injection of D-galactosamine hydrochloride by ear vein, a dose of 1.2 g/kg) and negative control group (5% Glucose). Clinical, biochemical and pathological changes of animals were observed. The expression of pigs fgl2 (pfgl2) mRNA in liver tissue was detected by real time RT-PCR, the expression of pfgl2 protein in liver tissue was detected by immunohistochemistry. RESULTS: A pig model of fulminant hepatic failure was successfully established using the D-galactose hydrochloride; Real time RT-PCR of liver fgl2 mRNA showed that fgl2 mRNA expression was increased significantly in liver tissue of fulminant hepatic failure pig model compared with the control group (P = 0.016); Immunohistochemical staining showed that there were fgl2 protein expression in liver tissue of fulminant hepatic failure pig model, mainly in the membrane and cytoplasm of hepatocytes, inflammatory cells, liver sinusoidal endothelial cells and vascular endothelial cells of liver cell necrosis region. However, there are no fgl2 positive staining on negative control. CONCLUSIONS: The pig model of fulminant hepatic failure induced by D-galactosamine hydrochloride is similar to human pathological process and can be used to evaluate the pre-clinical efficacy and safety of drug treatment on fulminant hepatic failure. Abnormal expression of pfgl2 at both mRNA level and protein level in the liver of fulminant hepatic failure pig model shows that pfgl2 induced coagulation pathway is also involved in the development of fulminant hepatic failure. Gene therapy targeting fgl2 genes for fulminant hepatic failure may provide a new means for the treatment of fulminant hepatic failure.

[Effects of Chinese medicine for regulating "sea of blood in brain" combined with bone marrow stromal stem cell transplantation on angiogenesis in ischemic brain tissue of rats].

OBJECTIVE: To observe whether Naomai Yihao (NM) Capsule, a compound traditional Chinese herbal medicine for regulating the "sea of blood in brain", and bone marrow stromal stem cell (BMSC) transplantation could improve angiogenesis in focal cerebral ischemia in rats. METHODS: A rat model of middle cerebral artery occlusion (MCAO) was established. The rats were divided into untreated group, NM group, BMSC group and combination of NM and BMSC group (combined treatment group). Another 8 normal rats were selected as sham-operated group. After 3-, 7- and 14-day reperfusion, behavioral rating scale (BRS) of the rats and histopathology of the cerebral tissue were evaluated. Expression of CD31 in the brain tissue was also measured by immunohistochemical method. RESULTS: Compared with the untreated group, BRSs of the NM group, BMSC group and combined treatment group were decreased significantly (P=0.000), but there was no interacting effect between NM and BMSC transplantation. Compared with the untreated group, the numbers of CD31 positive cells in NM group, BMSC group and combined treatment group were increased significantly (P=0.000), and there were interacting effects among NM, BMSC transplantation, and the observation time (P<0.01). After 14-day reperfusion, combination of NM and BMSC transplantation could largely increase the number of CD31 positive cells. CONCLUSION: NM is able to promote the angiogenesis and neurological impairment improvement in focal cerebral ischemia of rats which are administered with BMSC transplantation, and the effect is reinforced with the extension of treatment time.

The regulatory effect of the p38 signaling pathway on valdecoxib-induced apoptosis of the Eca109 cell line.

Valdecoxib is a second generation selective COX-2 inhibitor that can induce cell apoptosis in a variety of cell types, but its precise regulatory mechanism is unknown. Apoptosis of Eca109 cells and p38 mRNA expression were investigted. The expression of p-p38MAPK, Fas and FasL proteins were detected by immunohistochemical staining and FCM. Valdecoxib increased the apoptosis rate of Eca109 cells. Fas and FasL protein expression was up-regulated in the valdecoxib groups, while SB203580 partly inhibited the valdecoxib-induced overexpression. Valdecoxib increased p38MAPK expression, while SB203580 inhibited the overexpression of this protein and the apoptosis rate decreased. The expression of Fas, FasL and p38MAPK protein were positively correlated with the apoptotic rate. In conclusion, valdecoxib activates the p38MAPK pathway, thus up-regulating expression of the Fas and FasL proteins, which may be one of the mechanisms through which valdecoxib induces apoptosis.

[Dynamic changes in traditional Chinese medicine syndromes in patients with ischemic stroke treated by acupuncture].

OBJECTIVE: To explore the dynamic state of traditional Chinese medicine (TCM) syndromes in acute ischemic stroke patients within 30 days of onset when treated with acupuncture, and to analyze the discrimination effects of the functions based on "decision trees" in identification of TCM syndromes of ischemic stroke. METHODS: A total of 264 cases with acute ischemic stroke regularly treated by acupuncture were included. Unified syndrome questionnaire was made by document retrieval and expert advice. The syndrome elements of the patients with acute ischemic stroke were surveyed on any day of three time periods (days 0-3, 4-10 and 11-30). The study was performed on multi time dynamic state results and correlated factors of basic TCM syndromes of the 264 patients. Bayes discriminant function of four syndromes of acute ischemic stroke on the basis of "decision trees" was used for computing the rate of miscarriage justice by original test and cross-validation, and the discrimination effects of "decision trees" were evaluated too. RESULTS: Wind, phlegm, fire-heat, qi deficiency, blood stasis, and hyperactivity of yang due to yin deficiency syndromes were found in the patients with acute ischemic stroke treated by acupuncture on the first 30 days of onset, and the incidence rates were 80.7%, 68.9%, 52.7%, 50.8%, 29.2% and 25.0% respectively. The mean scores and incidence rates of the six syndromes decreased gradually on three-time-point, especially of blood stasis syndrome. The main combined-syndromes were two-syndrome, three-syndrome and four-syndrome, and three-syndrome was the most frequently encountered type. Single syndrome was not found in the patients with acute ischemic stroke on the first three days of onset. Two-syndrome combination types were wind-phlegm, wind-heat, wind combined with qi deficiency or phlegm stagnation due to qi deficiency, phlegm-heat and blood stasis combined with hyperactivity of yang due to yin deficiency, and the incidence rates were 54.5%, 42.8%, 40.9%, 39.4%, 35.6% and 3.8% respectively. The mean scores of phlegm and qi deficiency in high-age patients were higher than those in low-age patients. The mean score and incidence rate of qi deficiency in female patients were higher than those in male patients. The mean score of phlegm in female patients was higher than that in male patients. To simplify the "decision trees" composed of 21 items, the group of Bayes discriminant function including eight most significant items out of the original 21 items was set up. The discrimination effect of the eight items including reddish face, constipation, yellow tongue fur, short breath, bright-white or gray complexion, tinnitus, feverish palms and soles and scanty tongue fur was similar to that of the 21 items, and there was no significant difference between the two functions. CONCLUSION: Wind syndrome and phlegm syndrome are the major single syndromes occurring in acute ischemic stroke patients within 30 days of onset, and three-syndrome combination is the most frequent multiple syndrome type. After acupuncture treatment, some syndrome elements including wind, phlegm, fire-heat, qi deficiency, blood stasis, and hyperactivity of yang due to yin deficiency are gradually reduced, and combined syndrome type is gradually become simple. Eight syndrome element items including reddish face, constipation, yellow tongue fur, short breath, bright-white or gray complexion, tinnitus, feverish palms and soles and scanty tongue fur have important means in discriminating yin syndrome from yang syndrome and sthenia syndrome from asthenia syndrome.

[Characteristics of traditional Chinese medicine syndromes in patients with acute ischemic stroke of yin or yang syndrome: a multicenter trial].

OBJECTIVE: To explore the composition characteristics of traditional Chinese medicine (TCM) syndromes in patients with acute ischemic stroke of yin or yang syndrome by investigating the characteristics of TCM syndromes at different periods after onset. METHODS: One thousand two hundred and forty-six patients with acute ischemic stroke were admitted in twenty hospitals. According to the "diagnostic criteria of syndrome differentiation of stroke", the characteristics of syndromes in the patients were investigated at the periods of 1-3 days, 4-10 days and 11-30 days after they had ischemic stroke. General distribution of six basic syndromes was compared between the patients with yin syndrome and the patients with yang syndrome at the three periods. The six basic syndromes were wind syndrome, pathogenic fire syndrome, phlegm syndrome, blood stasis syndrome, qi deficiency syndrome, and syndrome of yin deficiency and yang hyperactivity. RESULTS: The percentages of wind, pathogenic fire, and phlegm syndromes in the patients were decreased at the period of 11-30 days as compared with the period of 1-3 days (87.1% vs 79.3%, 52.1% vs 38.7% and 67.1% vs 57.4% respectively, P<0.01). However, the percentages of the syndromes of blood stasis, qi deficiency, and yin deficiency and yang hyperactivity were similar at the three periods (P>0.05). There were no differences in the distribution of yin and yang syndromes among the three periods (P>0.05). The percentages of syndromes of wind, pathogenic fire, phlegm, and yin deficiency and yang hyperactivity were higher (P<0.01), and the percentages of syndromes of blood stasis and qi deficiency were lower (P<0.05, P<0.01) in patients with yang syndrome than in patients with yin syndrome. The complex of three syndromes was the most frequent composition pattern in the patients at the three periods. The percentages of complex syndromes of four or five syndromes were higher, and the percentages of single-syndromes and complex syndromes of two syndromes were lower in patients with yang syndrome than in patients with yin syndrome (P<0.05, P<0.01). The most frequent complex syndromes in patients with yin syndrome were complex syndrome of wind, phlegm, blood stasis and qi deficiency, and complex syndrome of wind, phlegm and qi deficiency; while the most frequent complex syndromes in patients with yang syndrome were complex syndrome of wind, pathogenic fire, phlegm and qi deficiency, and complex syndrome of wind, pathogenic fire and phlegm. CONCLUSION: The main discrimination between the yin and yang syndromes is that the yang syndrome is characterized by pathogenic fire. The syndromes of phlegm, qi deficiency, and blood stasis are not associated with the diagnosis of yin or yang syndrome.

[Effect evaluation for comprehensive treatment of acute stage of stroke].

OBJECTIVE: To explore the clinical evaluation system reflecting the superiority and characteristics of comprehensive traditional Chinese medicine (TCM) therapy for acute stroke. METHODS: A randomized controlled trial with single blind in various therapeutic centers was applied on the patients with the acute stage of hemorrhagic stroke due to hypertension, who were allocated to the trial group and the control group. The trial group accepted the general Western medicine therapy and differential treatment of traditional Chinese medicine based on stage classification. Patients in the control group were treated with the general Western medicine and the placebo of traditional Chinese herbal medicine. The treatment effect was assessed at the 7th day, 14th day, 21st day, and 28th day of post-treatment and after 3-month follow-up. The clinical evaluation system included the syndromes of TCM (ZH), Glasgow coma standard (GCS), nerve functional failure (NF), activity of daily living (ADL), Barther index (BI), quality of life index (QLI) and functional activities questionnaire (FAQ). RESULTS: Four hundred and four patients with acute stroke were included. There were 178 cases with yang-syndrome and 21 cases with yin-syndrome in the trial group (n=199), and there were 165 cases with yang-syndrome and 40 cases with yin-syndrome in the control group (n=205). The rates of recovery and obvious improvement after 3-month treatment in the trial group and the control group were 86.5% and 73.6% respectively. There was significant difference between the two groups (P<0.01). The response sensitivity of the effect items indicated that the sensitivity of GCS began to increase from the 7th day and was high at the 14th day and the 21st day for all patients. The response sensitivity of the NF scale was high for all patients at the 14th day, the 21st day and the 28th day. The BI scale and the QLI scale were sensitive to the patients with light and middle stage of stroke at the 21st day, and were sensitive to the patients with light stage of stroke after 3-month follow-up. The FAQ scale was sensitive to the light stroke at the 21st day and after 3-month follow-up. The ADL scale was sensitive to all patients at the 28th day and the patients with light stage of stroke after 3-month follow-up. The ZH scale was sensitive to all patients from 0 to 7d, the 14th day, and the 28th day. The principle components analysis indicated these 7 items could reflect the condition of stroke from 0-7d, the 21st day and after 3-month follow-up, and could be used to evaluate the therapeutic effect of hemorrhagic stroke. ZH scale and FAQ scale were more sensitive than other effect items at the 28th day. CONCLUSION: The seven items (GCSbNFbBIbQLIbFAQbADLbZH) have high sensibility to all patients in the acute stage of hemorrhage stroke especially at the 21st day. The ZH score will change in accord with the condition of stroke, and is appropriate to reflect the condition of stroke. It is believed that the seven items can form the system of effect evaluation in different stages of stroke, and the ZH scale is a very important item.

[Randomized multicenter control clinical study on acute ischemic stroke treatment with traditional Chinese medicine].

OBJECTIVE: To observe the effect of a comprehensive protocol of integrated Chinese and Western medicine (ICWM) in treating with acute ischemic stroke. METHODS: A multi-center, prospective, random and control clinical trial was adopted with 606 patients of acute ischemic stroke. They were divided into the treatment group (274 cases) treated with ICWM protocol, and the control group (263 cases) treated with Western medicine plus placebe, and BI, mRS were assessed after treatment. RESULTS: Compared with the control group, the 90th day assessment showed that the severe disability rate was lower (BI <75) (P <0.05), the complete reabilitation and mild disability rate (BI> or =95, P < 0.05), and the disability level (modified Rankin scale mRS) were improved (P <0.05) in the treatment group than those in the control group. CONCLUSION: The ICWM protocol used in this study may improve neural function and quality of life of acute ischemic stroke patients, and reduce the severe disability rate in those after 90 days treatment.

[Correlation of Skp2 expression in gastric carcinoma to expression of P27 and PTEN].

BACKGROUND & OBJECTIVE: S-phase kinase-associated protein 2 (Skp2) is a positive regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of cyclin-dependent kinase inhibitor P27. Its overexpression has been involved in cell transformation and tumorigenesis. This study was to investigate the significance of Skp2 expression in human gastric carcinoma and its correlation to expression of both P27 and PTEN. METHODS: The expression of Skp2 in 138 specimens of gastric cancer and their paired adjacent mucosa, 102 specimens of paired metastatic lymph nodes, 30 specimens of dysplasia, 30 specimens of intestinal metaplasia, 10 specimens of chronic superficial gastritis, and 5 specimens of normal gastric mucosa, and the expression of P27 and PTEN in 138 specimens of gastric cancer were detected by immunohistochemistry. RESULTS: Skp2 labeling frequency was significantly higher in intestinal metaplasia [(12.68+/-0.86)%] and adjacent mucosa [(19.32+/-1.22)%] than in chronic superficial gastritis [(0.53+/-0.13)%] and normal gastric mucosa [(0.47+/-0.19)%] (P<0.001), but there was no difference between chronic superficial gastritis and normal gastric mucosa (P>0.05); Skp2 labeling frequency was significantly higher in dysplasia [(16.74+/-0.82)%] than in intestinal metaplasia (P<0.001), significantly higher in primary gastric carcinoma [(31.34+/-2.17)%] than in dysplasia and adjacent mucosa (P<0.001), and significantly higher in metastatic lymph node [(39.76+/-2.00)%] than in primary gastric carcinoma (P=0.037). Skp2 labeling frequency in gastric carcinoma was positively correlated with differentiation grade (rs=0.315, P<0.001), vessel invasion (rs=0.303, P<0.001), and lymph node metastasis (rs=0.254, P=0.001). Skp2 expression was negatively correlated with both P27 expression (rs=-0.451, P<0.001) and PTEN expression (rs=-0.480, P<0.001) in gastric carcinoma. P27 expression was positively correlated with PTEN expression in gastric carcinoma (rs=0.642, P<0.001). CONCLUSION: Skp2 overexpression, which may lead to degradation of P27 and low expression of PTEN, may be a very important reason in carcinogenesis and progression of gastric carcinoma.

[Thinking and challenge induced by the hypothesis of breaking stagnant and eliminating blood stasis in Treating acute cerebral hemorrhage by rF VII a].

Definite therapeutic effect has obtained by TCM in treating acute cerebral hemorrhage (ACH) according the TCM theory of "blood circulating outside the vessels is the stasis" using breaking stagnant and eliminating blood stasis (Poxue Zhuyu) method, but no material involving the natural development of stoke in superacue stage (0 - 4 hrs after onset of the disease) being presented so far. It has been proved by randomized, double-blinded multi-centeric clinical trials that recombinant activated factor VII (rF VII a) could decreased the morbidity and disability of patients suffered from ACH, suggesting that use hemostasis treatment in ACH during superacu stage should be stressed, and the drugs for Poxue Zhuyu should be used cautiously in the period of 0 - 4 hrs after onset. The hemorrhagic disorder could be eliminated by using drugs for Poxue Zhuyu and other medicines in rational combination.

Relation of overexpression of S phase kinase-associated protein 2 with reduced expression of p27 and PTEN in human gastric carcinoma.

AIM: To investigate the significance of S phase kinase-associated protein 2 (Skp2) expression in human gastric carcinoma and the relation between expressions of Skp2, p27 and PTEN. METHODS: Immunohistochemical analysis was performed on 138 gastric carcinoma specimens, their paired adjacent mucosa specimens, 102 paired lymphatic metastatic carcinoma tissue specimens, 30 dysplasia specimens, 30 intestinal metaplasia specimens, 10 chronic superficial gastritis specimens and 5 normal gastric mucosa specimens for Skp2 expression and on 138 gastric carcinoma specimens for p27 and PTEN expression. RESULTS: Skp2 labeling frequency was significantly higher in intestinal metaplasia (12.68+/-0.86) and adjacent mucosa (19.32+/-1.22) than in normal gastric mucosa (0.53+/-0.13) and chronic superficial gastritis (0.47+/-0.19) (P = 0.000); in dysplasia (16.74+/-0.82) than in intestinal metaplasia (P = 0.000); in gastric primary carcinoma (31.34+/-2.17) than in dysplasia and adjacent mucosa (P = 0.000); in metastasis gastric carcinoma in lymph nodes (39.76+/-2.00) than in primary gastric carcinoma (P = 0.037), respectively. Skp2 labeling frequency was positively associated with differentiation degree (rho = 0.315, P = 0.000), vessel invasion (rho = 0.303, P = 0.000) and lymph node metastasis (rho = 0.254, P = 0.000) of gastric cancer. Expression of Skp2 was negatively associated with p27 (rho = -0.451, P = 0.000) and PTEN (rho = -0.480, P = 0.000) expression in gastric carcinoma. p27 expression was positively associated with PTEN expression in gastric carcinoma (rho = 0.642, P = 0.000). CONCLUSION: Skp2 overexpression may be involved in carcinogenesis and progression of human gastric carcinoma in vivo, possibly via p27 proteolysis. PTEN may regulate the expression of p27 by negatively regulating Skp2 expression.

Flow cytometric analysis of DNA, telomerase content and multi-gene expression in esophageal epithelial dysplasia.

AIM: To investigate the alteration of molecular events and the early carcinogenesis mechanism of esophageal epithelial cells in the high incidence area of esophageal cancer. METHODS: Esophageal epithelial cells of esophageal cancer patients were collected from the high incidence area in China. Content of DNA and telomerase as well as multi-gene expressions such as p53, p21 and cyclin D1 in esophageal precancer cells were quantitatively analysed by flow cytometry (FCM) with indirect immunofluorescence technique and DNA propidium iodide fluorescence staining. RESULTS: FCM analysis results showed the DNA content increased significantly and the heteroploid rate was 87.9% in occurred carcinogenesis. P53 protein accumulation and ras p21 increase were seen in the early carcinogenesis of the esophagus. The positive rate of p53 and ras p21 was 100% (5/5, 4/4 respectively) in the cancer group. Telomerase and oncogene cyclin D1 were over- expressed in all of the cancer patients. CONCLUSION: Increased DNA content and heteroploid rate, accumulation of p53 protein, and over-expression of p21, telomerase and cyclin D1 proteins were early molecular events during the development of esophageal cancer.