Bibliometric and visualized analysis of type 2 diabetic osteoporosis from 2013 to 2022.

Type 2 diabetic osteoporosis (T2DOP) has received increasing attention from researchers. In this study, a total of 453 publications related to T2DOP from 2013 to 2022 were analyzed using bibliometric and visual analysis to identify the research trends and research hotspots in the field of T2DOP. PURPOSE: The objective of this study was to conduct a comprehensive bibliometric analysis of T2DOP-related publications from 2013 to 2022 to determine global research trends in T2DOP in terms of number of publications, countries/regions, institutions, authors, journals, funding agencies, and keywords. METHODS: All data were collected from the Web of Science Core Collection (WoSCC). All original research publications regarding T2DOP from 2013 to 2022 were retrieved. VOSviewer and Microsoft Office Excel were used to conduct the bibliometric and visual analysis. RESULTS: From 2013 to 2022, 515 relevant publications were published, with a peak in 2022 in the annual number of publications. The countries leading the research were USA and China. Sugimoto was the most influential authors. Capital Medical University and Nanjing Medical University were the most prolific institutions. Osteoporosis International was the most productive journal concerning T2DOP research. National Natural Science Foundation of China was the primary funding source for this research area. "Bone-mineral density", "fracture risk", and "postmenopausal women" were the most high-frequency keywords over the past 10 years. CONCLUSION: This was the first bibliometric study of diabetes mellitus and osteoporosis to exclusively examine type 2 diabetes mellitus. Our findings would provide guidance to understand the research frontiers and hot directions in the near future.

Rice Bran Supplementation Ameliorates Gut Dysbiosis and Muscle Atrophy in Ovariectomized Mice Fed with a High-Fat Diet.

Rice bran, a byproduct of rice milling, is rich in fiber and phytochemicals and confers several health benefits. However, its effects on gut microbiota and obesity-related muscle atrophy in postmenopausal status remain unclear. In this study, we investigated the effects of rice bran on gut microbiota, muscle synthesis, and breakdown pathways in estrogen-deficient ovariectomized (OVX) mice receiving a high-fat diet (HFD). ICR female mice were divided into five groups: sham, OVX mice receiving control diet (OC); OVX mice receiving HFD (OH); OVX mice receiving control diet and rice bran (OR); and OVX mice receiving HFD and rice bran (OHR). After twelve weeks, relative muscle mass and grip strength were high in rice bran diet groups. IL-6, TNF-α, MuRf-1, and atrogin-1 expression levels were lower, and Myog and GLUT4 were higher in the OHR group. Rice bran upregulated the expression of occludin and ZO-1 (gut tight junction proteins). The abundance of Akkermansiaceae in the cecum was relatively high in the OHR group. Our finding revealed that rice bran supplementation ameliorated gut barrier dysfunction and gut dysbiosis and also maintained muscle mass by downregulating the expression of MuRf-1 and atrogin-1 (muscle atrophy-related factors) in HFD-fed OVX mice.

The clinical implications and molecular features of intrahepatic cholangiocarcinoma with perineural invasion.

BACKGROUND: Perineural invasion (PNI) is associated with metastasis in malignancies, including intrahepatic cholangiocarcinoma (ICC), and is correlated with poor prognosis. METHODS: The study included three large cohorts: ZS-ICC and TMA cohorts from our team, MSK cohort from a public database, and a small cohort named cohort 4. Prognostic implications of PNI were investigated in MSK cohort and TMA cohort. PNI-related genomic and transcriptomic profiles were analyzed in MSK and ZS-ICC cohorts. GO, KEGG, and ssGSEA analyses were performed. Immunohistochemistry was used to investigate the relationship between PNI and markers of neurons, hydrolases, and immune cells. The efficacy of adjuvant therapy in ICC patients with PNI was also assessed. RESULTS: A total of 30.6% and 20.7% ICC patients had PNI in MSK and TMA cohorts respectively. Patients with PNI presented with malignant phenotypes such as high CA19-9, the large bile duct type, lymph node invasion, and shortened overall survival (OS) and relapse-free survival (RFS). Nerves involved in PNI positively express tyrosine hydroxylase (TH), a marker of sympathetic nerves. Patients with PNI showed high mutation frequency of KRAS and an immune suppressive metastasis prone niche of decreased NK cell, increased neutrophil, and elevated PD-L1, CD80, and CD86 expression. Patients with PNI had an extended OS after adjuvant therapy with TEGIO, GEMOX, or capecitabine. CONCLUSION: Our study deciphered the genomic features and the immune suppressive metastasis-prone niche in ICC with PNI. Patients with PNI showed a poor prognosis after surgery but a good response to adjuvant chemotherapy.

CTLA-4 Synergizes With PD1/PD-L1 in the Inhibitory Tumor Microenvironment of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is highly invasive and carries high mortality due to limited therapeutic strategies. In other solid tumors, immune checkpoint inhibitors (ICIs) target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD1), and the PD1 ligand PD-L1 has revolutionized treatment and improved outcomes. However, the relationship and clinical significance of CTLA-4 and PD-L1 expression in ICC remains to be addressed. Deciphering CTLA-4 and PD-L1 interactions in ICC enable targeted therapy for this disease. In this study, immunohistochemistry (IHC) was used to detect and quantify CTLA-4, forkhead box protein P3 (FOXP3), and PD-L1 in samples from 290 patients with ICC. The prognostic capabilities of CTLA-4, FOXP3, and PD-L1 expression in ICC were investigated with the Kaplan-Meier method. Independent risk factors related to ICC survival and recurrence were assessed by the Cox proportional hazards models. Here, we identified that CTLA-4+ lymphocyte density was elevated in ICC tumors compared with peritumoral hepatic tissues (P <.001), and patients with a high density of CTLA-4+ tumor-infiltrating lymphocytes (TILsCTLA-4 High) showed a reduced overall survival (OS) rate and increased cumulative recurrence rate compared with patients with TILsCTLA-4 Low (P <.001 and P = .024, respectively). Similarly, patients with high FOXP3+ TILs (TILsFOXP3 High) had poorer prognoses than patients with low FOXP3+ TILs (P = .021, P = .034, respectively), and the density of CTLA-4+ TILs was positively correlated with FOXP3+ TILs (Pearson r = .31, P <.001). Furthermore, patients with high PD-L1 expression in tumors (TumorPD-L1 High) and/or TILsCTLA-4 High presented worse OS and a higher recurrence rate than patients with TILsCTLA-4 LowTumorPD-L1 Low. Moreover, multiple tumors, lymph node metastasis, and high TumorPD-L1/TILsCTLA-4 were independent risk factors of cumulative recurrence and OS for patients after ICC tumor resection. Furthermore, among ICC patients, those with hepatolithiasis had a higher expression of CTLA-4 and worse OS compared with patients with HBV infection or undefined risk factors (P = .018). In conclusion, CTLA-4 is increased in TILs in ICC and has an expression profile distinct from PD1/PD-L1. TumorPD-L1/TILsCTLA-4 is a predictive factor of OS and ICC recurrence, suggesting that combined therapy targeting PD1/PD-L1 and CTLA-4 may be useful in treating patients with ICC.

Cancer survival in patients from a hospital-based cancer registry, China.

Purpose: There are few reports on survival rate analysis from hospital-based cancer registries (HBCR) in China, although the National Center of Cancer Registry of China has launched such an effort with the mission to expand the scope of registration and follow-up. Our study aimed to evaluate survival and outcomes of cancer patients from a HBCR in eastern China. Methods: Active and passive follow-up methods were used to obtain information on survival status for all patients from Qidong City and Haimen City in the databases of our hospital-based registrations from 2002 to 2014. Censor time for survival was 31st March, 2016. Survival probability was estimated using the life-table method with SPSS Statistics software, and comparison of significant differences in survival rates was tested by Wilcoxon (Gehan) statistic. Results: The outcomes of 5010 patients were identified in the follow-up for 5244 cases from Qidong and Haimen, with a follow-up rate of 95.65%, and a rate of lost to follow-up of 4.35%. The 1-, 3-, 5-, and 10-year observed survival (OS) rate in all-combined cancer sites were 59.80%, 37.70%, 30.82%, and 22.60%, respectively. The top 10 cancer sites in rank were cancers of lung, esophagus, liver, cervix, stomach, breast, colon-rectum, non-Hodgkin's lymphoma, nasopharynx, and ovary, with 5-year OS rates of 12.63%, 19.62%, 11.69%, 66.61%, 21.35%, 59.43%, 36.36%, 37.03%, 48.95% and 36.17%, respectively. Females experienced better survival than males for lung, esophageal, liver, nasopharyngeal and pancreatic cancers (P<0.05), but not for other sites (P>0.05). A significant difference was also found between males and females when all-sites were combined (P<0.01). There are significant differences (P<0.05) between the 2015 patients (from Qidong) and the 3001 patients (from Haimen) with 5-year OS rates of 32.72% vs 29.57%; no significant differences were found for 5-year OS rates for individual cancer sites (P>0.05) except for liver (P=0.0005) and ovary (P=0.0460) between the two cities. Younger patients had better prognosis, but significance was only seen in cervical (P=0.0102) and nasopharyngeal (P=0.0305) cancers. Conclusion: The survival rates of each site or of all sites-combined in this setting are consistent with those elsewhere in China and abroad. Discrepancies in overall survival could be affected by the proportion of sites with or without better prognosis. Hospital-based cancer survival is a better index to evaluate outcomes that reflect the levels of comprehensive treatment and improvement of medical and health services.

[Expression and role of CXC chemokine 5 in liver cancer cells].

OBJECTIVE: To explore the expression of CXC chemokine 5 (CXCL5) in liver cancer cells and its effect on cell proliferation, migration and invasion. METHODS: Real-time (RT)-PCR and enzyme-linked immunosorbent assay (ELISA) were used to detect the mRNA and protein levels of CXCL5 in 4 liver cancer cell lines with different metastatic potentials (in ascending order: HepG2, SMMC7721, MHCC97L and MHCC97H). HepG2 with a low expression of CXCL5 was treated with CXCL5. There were four groups: 0 nmol/L CXCL5, 0.1 nmol/L CXCL5, 1.0 nmol/L CXCL5 and 10.0 nmol/L CXCL5. Cell proliferation was evaluated by cell counting kit-8 (CCK-8) assay. Transwell chambers and basement membrane matrix (Matrigel) were used to observe the cellular migration and invasion. Statistical analysis was performed with SPSS 16.0. Statistical comparison of the results was made by analysis of variance (ANOVA). RESULTS: The relative mRNA expression levels of CXCL5 in HepG2, SMMC7721, MHCC97L and MHCC97H were 0.002% ± 0.000%, 0.005% ± 0.000%, 1.030% ± 0.070% and 0.980% ± 0.190% (F = 33.88, P < 0.01) while their protein levels 14.3 ± 0.4, 25.7 ± 1.4, 82.8 ± 3.2 and 98.9 ± 1.7 respectively (F = 447.08, P < 0.01). The CCK-8 results showed that cell proliferation increased with the treatment of CXCL5, but no significant difference existed (F < 1.00, P > 0.05), cell numbers of migration of 0, 0.1, 1.0, 10.0 nmol/L CXCL5 groups were 29 ± 3, 56 ± 16, 113 ± 7 and 130 ± 15 (F = 51.94, P < 0.01), while cell numbers of invasion 17.3 ± 1.8, 33.0 ± 3.2, 65.7 ± 4.4 and 94.3 ± 3.5 respectively (F = 104.13, P < 0.01). CONCLUSIONS: Liver cancer cells with high metastatic potential have a higher expression of CXCL5. And exogenous CXCL5 can increase the proliferation, migration and invasion of liver cancer cells with low metastatic potential. Thus CXCL5 may be associated with the metastasis of liver cancer.

[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.

Considerations on intervention goal and efficacy evaluation of traditional Chinese medicine in the treatment of neurological diseases.

In the last several years, traditional Chinese medicine (TCM) has made much progress in the treatment of neurological diseases. The living space of TCM in neurological diseases lies in refractory diseases, aging and chronic diseases caused by multiple factors as well as sub-health state and chronic fatigue state. The effect model of TCM mainly consists of whole effect, self-organization, self-stable model, holographic effect and butterfly effect. The effective point of TCM in neurological diseases lies mainly in end-points and health-related events. Moreover, TCM has advantages in the evaluation of symptoms, syndrome and quality of life (QOL). Some key indexes should be included when evaluating the efficacy of TCM in neurological diseases. Meanwhile, the advantages of TCM such as end-points, health-related events and QOL should be highlighted. Multi-subject researching methods could be adopted to make a comprehensive evaluation of subjective and objective indexes. The clinical evidence on the TCM efficacy evaluation may come from RCTs, and other types of designs can also be considered.

[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.

[Influence of Naomai II capsule on dynamic expression of protease-activated receptors-1 after acute intracerebral hemorrhage].

OBJECTIVE: To study the dynamic expression of protease-activated receptor-1(PAR-1) after acute intracerebral hemorrhage (ICH) and the influence of Naomai capsule (NMC II) on the expression in rats. METHOD: 72 rats were randomly divided into 9 groups (n = 8 in each group). They were normal group, ICH model groups at 6, 24 h, 3, 7 d and NMC II groups at 6, 24 h, 3, 7 d. ICH models were induced by collagenase type VII-S. Immunohistochemical method was used to detect PAR-1 protein and RT-PCR technique was used to detect PAR-1mRNA in brain tissue around the haematoma at different groups. RESULT: PAR-1 protein and mRNA were mild positive in normal group. In model groups, intensity of PAR-1 expression started to enhance at 6 h, and enhanced more at 24 h. PAR-1 expression reached the peak at 3 d and began to descend. At 7 d the decent was obvious. At 6, 24 h, 3, 7 d time point. The PAR-1 protein positive cell number and PAR-1 mRNA absorbance ratio in ICH model and NMC II groups were significantly higher than those in normal group (P < 0.05 or P < 0.01). The PAR-1 protein positive cell number and PAR-1mRNA absorbance ratio in NMC II group were significantly lower than those in ICH model group (P < 0.05 or P < 0.01). CONCLUSION: After ICH, PAR-1 is continuously activated because of the simulation of thrombin. Function of thrombin after ICH maybe mediated by PAR-1; NMC II may inhibit the expression of PAR-1. This may be one of the main therapeutics mechanisms of NMC II.

[Treatment of acute intracerebral hemorrhage with a comprehensive protocol of integrated Chinese and Western medicine].

OBJECTIVE: To observe the effect and safety of a comprehensive protocol of integrated Chinese and Western medicine (ICWM) in treating acute intracerebral hemorrhage (AICH). METHODS: A multi-center, single blinded, random and control clinical trial was adopted with 404 patients with AICH, they were divided into the treatment group (199 cases) treated with ICWM protocol, and the control group (205 cases) treated with Western medicine plus placebo, and AICH related indexes were assessed after treatment. RESULTS: Compared with the control group, the neurological deficit score (National Institute of Health Stroke Scale, NIHSS) determined on the 28th and the 90th day after treatment was ameliorated in the treatment group (P < 0.01). Moreover, the 90th day assessment showed that the mortality and severe disability rate was lower (BI < 75) (P <0.05), the complete rehabilitation and mild disability rate (BI > or = 95, P < 0.05), and the sociability rate (Functional Assessment Questionnaire, FAQ) were higher (P < 0.01) in the treatment group than those in the control group. The incidence of adverse reaction was 5.53%, manifested as non-infective diarrhea. CONCLUSION: The ICWM protocol used in this study may improve neural function and quality of life of AICH patients, and reduce the mortality and severe disability rate in those after 90 days' treatment, with only non-infective diarrhea as the adverse reaction.

[Observation of the effect of early fluid resuscitation on hepatic fatty degeneration in rats after severe scald].

OBJECTIVE: To investigate the efficacy of early fluid resuscitation on hepatic steatosis in rats after severe scald. METHODS: One hundred and forty-four Sprague-Dawley rats were enrolled in the study. In thirty-six rats skin of 30% TBSA was treated with cold water to serve as sham injury group. All other rats were inflicted with 30% full-thickness scald, and they were subdivided into 3 groups, i. e. scald group(S, without resuscitation), delayed resuscitation group ( DR, with Ringer's solution at 6 post-scald hour(PSH) ) and early resuscitation group( ER, with Ringer's solution immediately after scald). The hepatic tissues of the rats were harvested at 0.5, 1.0,2.0,3.0,7.0 post-scald hour( PSH) and on 21.0 PSD for the observation of pathological changes with light-microscope and transmission electron microscope. The serum contents of TC, TG, HDL, ALP were determined at the same time-points. Body weight of each rat was measured before blood sampling, and total liver weight after blood sampling. Liver weight/body weight ratio was recorded. RESULTS: Compared with sham injury group, the fat denaturation degree of hepatic tissue in ER group was obviously less than that in S and DR group . The serum level of high density lipoprotein (TC) , triglyceride ( TG) , and alkaline phosphatase (ALP) after scald increased ranking as S > DR > ER, while the level of HDL decreased in that order. The liver weight/body weight ratio of the rats in DR group on 1.0 PSD was obviously elevated compared with that in ER group( P <0. 05) , and there exhibited significant difference of liver weight/body weight ratio between DR and ER groups on 7. 0 PSD ( P < 0. 01). The liver steatosis had obvious negative correlation with HDL content after scald( r = -0. 37, P <0.01) , but it had positive correlation with the ALP content( r = 0. 45, P <0. 01), TG content( r = 0. 25, P <0. 01) and liver weight/body weight ratio( r = 0. 440, P <0. 01). The remaining parameters showed no correlation with the liver steatosis. CONCLUSION: Fluid resuscitation immediately after scald can ameliorate hepatic fatty degeneration, reduce its incidence, and beneficial to recovery of liver damage to a certain extent.

[A Meta-analysis in multi-center random controlled clinical trials].

OBJECTIVE: To study the center effect discrepancy in the multi-center clinical trials. METHODS: Two groups of data collected from the multi-center clinical trials were used. Data were processed by covariance analysis and Meta-analysis. RESULTS: In the covariance analysis, the discrepancy of the center effect values indicated statistical significance. Through Meta-analysis on fixed effect model, the discrepancy in one heterogeneity test showed no statistical significance (P > 0.05) while the inter-group discrepancy of the merged effect values drawn from analysis based on fixed effect model having statistical significance (P < 0.05). In the random effect model, the discrepancy in one heterogeneity test showed statistical significance (P < 0.05) while the inter-group discrepancy of the merged effect values drawn from analysis based on random effect model having no statistical significance (P > 0.05). CONCLUSIONS: Studies on multi-center random controlled clinical trials, when statistical significance was found in the interaction discrepancy between the inter-center and the center-group relation, the merged effect values should be compared and analyzed by an appropriate statistic model based on the heterogeneous test results from the Meta-analysis. However, if the result from covariance analysis and the one from Meta-analysis did not agree to each other, the results drawn from the Meta-analysis were reliable.

[Origin and development of hemorrhagic stroke].

Research works were done on origin and development of the denomination, the acute stage of etiopathogenisis and pathogenesis, therapeutical priniciple and therapeutical methods in hemorrhagic stroke. Stroke was divided into is chemic and hemorrhagic until the end of the Qing dynasty. In 1997, Terminology of Traditional Chinese Medicine Treatment-Disease Part of National Standard formally included the term hemorrhagic stroke. Before 1950s-1960s, the pathogenesis emphasizes the up-stirring of liver, the adverse-rising of both blood and qi. A proper remedy should to subdue the liver yang, calm down the endopathic wind and clear heat. Since 1970s, it has been considered that the disorder is closely related with the spleen and stomach. The focal pathogenesis was blocked passage of the middle jiao, disorder of qi in ascending and descending and the abnormal flow of qi and blood. Since 1980s, it was claimed that hemorrhagic stroke belongs to blood syndrome of TCM. The vital pathogenesis was accumulation of blood stasis in acute stage of hemorrhagic stroke. The key point of therapeutical method was to promote blood circulation to remove blood stasis. In recent years, the theories of endogenous toxic factor, consumption, yin and yang syndrome, and the therapeutical method of antidote, assisting the vital qi, especially the development of common therapeutical methods were developed, with an abundance of differential diagnosis and treatment in hemorrhagic stroke.