ObjectiveTo explore the common syndrome elements of cerebral ischemic stroke （CIS） complicated with obstructive sleep apnea-hypopnea syndrome （OSAHS）， reveal the characteristics of traditional Chinese medicine （TCM） syndromes of the disease， clarify the syndrome differentiation and syndrome types， provide evidence for clinical syndrome differentiation， and provide reference for establishing the TCM syndrome type standards of CIS complicated with OSAHS. MethodThe clinical information form of CIS complicated with OSAHS formulated by the research group was used for syndrome survey， and the four-examination information of 300 patients with CIS complicated with OSAHS was collected. The four-examination information of patients was analyzed by latent structure method and comprehensive cluster analysis， and the common syndrome elements of CIS complicated with OSAHS were extracted by combining the TCM basic theory and clinical experience. On this basis， the characteristics of TCM syndromes and the syndrome types in line with reality were summarized. ResultThe top five syndrome elements in patients with CIS and OSAHS are sleep snoring， open mouth breathing， physical obesity， night awakening and dizziness. The top five tongue and pulse manifestations are enlarged tongue， slippery pulse， slippery coating， thick and white coating and purple tongue. The disease locations are the lung， spleen， stomach， kidney， liver and brain. The nature of disease includes deficiency， depression， blood stasis， phlegm， dampness and fire. The clinical syndrome types include the syndrome of stagnation of phlegm and dampness， syndrome of phlegm-dampness blocking the mind， syndrome of spleen deficiency with dampness， syndrome of Yin deficiency leading to fire hyperactivity， syndrome of Qi depression blocking collaterals， syndrome of liver depression and blood stasis， syndrome of Qi deficiency with dampness， and syndrome of Yang deficiency induced water retention. ConclusionIn addition to the common phlegm-， dampness- and blood stasis-related syndromes in patients with CIS and OSAHS， there are also depression- and deficiency-related syndromes. The main etiology and pathogenesis is the disturbance of Qi movement. In clinical practice， attention should be paid to the specific situation of individual patients to differentiate between deficiency and excess， and the treatment should be performed by the method of soothing and reinforcing， or unblocking and clearing， or both.

ObjectiveTo observe the effects of Jianpi Bushen Huoxue prescription （JPBSHX） on rat brain microvascular endothelial cells （RBMECs） based on hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） signaling pathway， aiming to provide a theoretical basis for the treatment of ischemic stroke. MethodTwelve 8-week-old male SPF-grade SD rats were selected. Eight of them were randomly chosen and given 3.25 g·mL^-1 JPBSHX solution by gavage at a dose of 10 mL·kg^-1 for 5 consecutive days to prepare the medicated serum， which was then preserved for later use. The remaining four rats were given the same volume of normal saline. Follow-up operations were the same as those of the above eight rats. Normal rat serum was collected and stored for later use. RBMECs were revived， cultured， passaged， and randomly divided into five groups： normal group （20% normal rat serum+80% high glucose DMEM）， model group （hypoxia-reoxygenation injury） （20% normal rat serum+80% glucose-free DMEM）， medicated serum group （20% JPBSHX-medicated serum+80% glucose-free DMEM）， medicated serum+HIF-1α inhibitor group （20% JPBSHX-medicated serum+HIF-1α inhibitor 1 mg +80% glucose-free DMEM）， and medicated serum+VEGF inhibitor group （20% JPBSHX-medicated serum +VEGF inhibitor 1 mg+80% glucose-free DMEM）. The relative protein expression levels of Claudin-1 and Claudin-5 in RBMECs， the expression levels of HIF-1α and VEGF in RBMEC culture supernatants， the repair ability of RBMECs， and the number of nodes， microvessels， and their lengths after 72 h of culture were observed in each group. ResultAfter 24 h of reoxygenation， the scratch healing rate in the model group was significantly lower than in the normal group （P<0.01）. Compared with the result in the model group， the scratch healing rates significantly improved in the medicated serum group， medicated serum+HIF-1α inhibitor group， and medicated serum+VEGF inhibitor group （P<0.05）. However， the healing rates in the medicated serum+HIF-1α inhibitor group and medicated serum+VEGF inhibitor group were significantly lower than that in the medicated serum group （P<0.05）. The number of nodes， microvessels， and total length of microvessels in the model group were significantly lower than those in the normal group （P<0.01）. These indicators significantly improved in the medicated serum group， medicated serum+HIF-1α inhibitor group， and medicated serum+VEGF inhibitor group compared with those in the model group （P<0.05）， but were significantly lower in the medicated serum+HIF-1α inhibitor group and medicated serum+VEGF inhibitor group compared with those in medicated serum group （P<0.05）. The relative expression levels of Claudin-1 and Claudin-5 proteins were significantly lower in the model group than in the normal group （P<0.01）. These levels were significantly higher in medicated serum group， medicated serum+HIF-1α inhibitor group， and medicated serum+VEGF inhibitor group than those in the model group （P<0.05）， but were significantly lower in the medicated serum+HIF-1α inhibitor group and medicated serum+VEGF inhibitor group than those in the medicated serum group （P<0.05）. The expression levels of HIF-1α and VEGF in the RBMEC culture supernatants were significantly lower in the model group than those in the normal group （P<0.01）. These levels were significantly higher in the medicated serum group， medicated serum+HIF-1α inhibitor group， and medicated serum+VEGF inhibitor group than those in the model group （P<0.05）， but were significantly lower in the medicated serum+HIF-1α inhibitor group and medicated serum+VEGF inhibitor group than those in the medicated serum group （P<0.05）. ConclusionJPBSHX can promote the proliferation， migration， and angiogenesis， such as tubule formation， of RBMECs damaged by hypoxia-reoxygenation injury， and this effect may be achieved through the regulation of the HIF-1α/VEGF signaling pathway.

Cardiomyopathy, Dilated/metabolism* ; Humans ; Microfilament Proteins/metabolism* ; Models, Cardiovascular ; Mutation ; Myocytes, Cardiac ; Pluripotent Stem Cells/metabolism* ; Transcription Factors/metabolism* ; Troponin T/metabolism*

Objective:To study the efficacy of different systemic chemotherapy regimens as first-line and second-line therapy and to determine the prognostic factors for patients with advanced biliary tract cancer.Methods:The clinical data of patients with advanced biliary tract cancer who underwent systemic chemotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2011 to December 2018 were studied. The efficacy of chemotherapy on objective response rate (ORR) and disease control rate (DCR) were evaluated. Potential prognostic factors for survival were studied using the Cox proportional hazards models.Results:Of 151 patients enrolled into this study, there were 75 males and 76 females, with ages ranging from 31 to 77 years (median 58 years). Two treatment protocols were used: (1) 104 patients received a gemcitabine-based regimen (combined with platinums or fluorouracils) or a combination of platinums and fluorouracils, while (2) 47 patients received a combination of albumin-bound paclitaxel and S-1. The corresponding ORR for each group were 15.4%(16/104) and 27.6%(13/47), respectively, and the DCR were 65.4%(68/104) and 72.3%(34/47), respectively. Of 58 evaluable patients who received chemotherapy as a second-line therapy, 31 patients received the regimen containing gemcitabine, platinums or fluorouracils with an ORR of 3.2% (1/31) and a DCR of 35.5%(11/31); a total of 18 patients received the taxanes-based regimen with an ORR of 11.1%(2/18) and a DCR of 38.9%(7/18); 9 patients received the irinotecan-based regimen with an ORR of 22.2%(2/9) and a DCR of 44.4%(4/9). Univariate analysis showed positive liver metastasis and elevated carbohydrate antigen (CA)19-9 level to be significantly correlated with worse survival outcomes ( HR=1.540, 95% CI: 1.019-2.328, P=0.040 and HR=1.892, 95% CI: 1.123-3.188, P=0.017). Conclusion:For patients with advanced biliary tract cancer, in addition to the conventional regimens containing gemcitabine, platinums and fluorouracils, the combination of albumin-bound paclitaxel and S-1 was shown to be an effective chemotherapeutic regimen for these patients. Second-line chemotherapy was insufficient and ineffective, and an irinotecan-based regimen deserves to be further investigated. Liver metastasis and elevated CA19-9 level were worse prognosis after chemotherapy for patients with advanced biliary tract cancer.

Objective:To explore the clinicopathological characteristics and prognosis of patients with ovarian metastases from colorectal cancer.Methods:A total of 122 female patients with ovarian metastases from colorectal cancer underwent treatment in Cancer Hospital, Chinese Academy of Medical Sciences between 2010 and 2015 were recruited. The clinicopathological features, treatment details and survival data of these patients were retrospectively analyzed. Kaplan-Maier method was used for survival analysis, log rank test and Cox proportional hazards model were used for prognostic factor analysis.Results:The median overall survival (OS) was 19.7 months. The 1-year, 3-years and 5-years OS rates were 72.1%, 24.7% and 9.9%, respectively. A total of 99 (81.1%) patients underwent oophorectomy. The median OS of patients who underwent oophorectomy was 21.9 months, significantly longer than 10.3 months of patients without oophorectomy ( P<0.01). Ovary as the only site of metastasis, primary tumor resection, and oophorectomy were associated with improved survival (all P<0.01). Primary tumor resection and oophorectomy were independent prognostic factors for OS (both P<0.01). Conclusion:Patients with ovarian metastases from colorectal cancer might acquire a survival benefit from surgical resection of the primary tumor and ovaries.

Objective:To explore the clinicopathological characteristics and prognosis of patients with ovarian metastases from colorectal cancer.Methods:A total of 122 female patients with ovarian metastases from colorectal cancer underwent treatment in Cancer Hospital, Chinese Academy of Medical Sciences between 2010 and 2015 were recruited. The clinicopathological features, treatment details and survival data of these patients were retrospectively analyzed. Kaplan-Maier method was used for survival analysis, log rank test and Cox proportional hazards model were used for prognostic factor analysis.Results:The median overall survival (OS) was 19.7 months. The 1-year, 3-years and 5-years OS rates were 72.1%, 24.7% and 9.9%, respectively. A total of 99 (81.1%) patients underwent oophorectomy. The median OS of patients who underwent oophorectomy was 21.9 months, significantly longer than 10.3 months of patients without oophorectomy ( P<0.01). Ovary as the only site of metastasis, primary tumor resection, and oophorectomy were associated with improved survival (all P<0.01). Primary tumor resection and oophorectomy were independent prognostic factors for OS (both P<0.01). Conclusion:Patients with ovarian metastases from colorectal cancer might acquire a survival benefit from surgical resection of the primary tumor and ovaries.

Objective:Anlotinib is an oral multi-target tyrosine kinase inhibitor (TKI) with dual effects of anti-proliferation and anti-angiogenesis. Phase Ⅰ clinical trials showed anlotinib was well tolerated and had therapeutic effects on a variety of tumors. The aim of this study is to explore the safety and efficacy of anlotinib in the treatment of metastatic renal cell carcinoma.Methods:Between January 2014 and November 2015, a single-center data was obtained from a phase Ⅱ clinical study of anlotinib versus sunitinib on advanced renal cell carcinoma and a phase Ⅱ clinical study of anlotinib on advanced renal cell carcinoma which failed to respond to TKI treatment. Kaplan-Meier method was used for survival analysis, while Log-rank test was used to compare the survival rates.Results:A total of 36 patients with advanced renal cell carcinoma were enrolled in this study, including 19 patients without any target drug treatment, 12 patients with sunitinib treatment and 5 patients with sorafenib treatment. The median number of treatment cycle was 16. Partial response (PR) was obtained in 11 patients (30.6%) and stable disease (SD) was obtained in 24 patients (66.7%). The disease control rate (DCR) was 97.2%. The median progression free survival (PFS) was 12.6 months, the 1-year survival rate was 80.6%, and the median survival time was 22.2 months. Up to the follow-up deadline, 3 patients still received treatment, the PFSs were 52.6 months, 65.0 months, and 66.7 months. The most common treatment-related adverse events of grade 3 or 4 included hypertension (19.4%), hand-foot skin reaction (11.1%), proteinuria (5.6%) and anemia (5.6%).Conclusions:Anlotinib shows good anti-tumor activity and is generally well-tolerated in the treatment of advanced renal cell carcinoma. The adverse reactions of anlotinib are milder than sunitinib or pazopanib.

Objective:Anlotinib is an oral multi-target tyrosine kinase inhibitor (TKI) with dual effects of anti-proliferation and anti-angiogenesis. Phase Ⅰ clinical trials showed anlotinib was well tolerated and had therapeutic effects on a variety of tumors. The aim of this study is to explore the safety and efficacy of anlotinib in the treatment of metastatic renal cell carcinoma.Methods:Between January 2014 and November 2015, a single-center data was obtained from a phase Ⅱ clinical study of anlotinib versus sunitinib on advanced renal cell carcinoma and a phase Ⅱ clinical study of anlotinib on advanced renal cell carcinoma which failed to respond to TKI treatment. Kaplan-Meier method was used for survival analysis, while Log-rank test was used to compare the survival rates.Results:A total of 36 patients with advanced renal cell carcinoma were enrolled in this study, including 19 patients without any target drug treatment, 12 patients with sunitinib treatment and 5 patients with sorafenib treatment. The median number of treatment cycle was 16. Partial response (PR) was obtained in 11 patients (30.6%) and stable disease (SD) was obtained in 24 patients (66.7%). The disease control rate (DCR) was 97.2%. The median progression free survival (PFS) was 12.6 months, the 1-year survival rate was 80.6%, and the median survival time was 22.2 months. Up to the follow-up deadline, 3 patients still received treatment, the PFSs were 52.6 months, 65.0 months, and 66.7 months. The most common treatment-related adverse events of grade 3 or 4 included hypertension (19.4%), hand-foot skin reaction (11.1%), proteinuria (5.6%) and anemia (5.6%).Conclusions:Anlotinib shows good anti-tumor activity and is generally well-tolerated in the treatment of advanced renal cell carcinoma. The adverse reactions of anlotinib are milder than sunitinib or pazopanib.

OBJECTIVE： To investigate the effects of Buyang huanwu decoction on the expression of MMPs and TIMPs in cardiac tissue of viral myocarditis （VMC） model mice. METHODS： Male BALb/c mice were randomly divided into control group， model group， positive control group [captopril， 100 mg/（kg·d）]， Buyang huanwu decoction low-dose， medium-dose and high-dose groups [6， 18， 36 g/（kg·d）]， with 24 mice in each group. Except for control group， other groups were given Coxsackie virus B3 once intraperitoneally to induce VMC model. After modeling， control group and model group were given constant volume of normal saline intragastrically； administration groups were given relevant medicine intragastrically； once a day， for consecutive 30 days. The general situation of mice in each group was observed. The day of inoculation was set at 0 d， heart mass to body mass ratio （HW/BW） was measured at 4， 10， 20， 30 d after inoculation. The morphological characteristics of myocardium were observed by HE staining， and the myocardial histopathological scores of myocardium were evaluated. The distribution of type Ⅰ and Ⅲ collagen in myocardium was observed by Abcam picrosirius red staining， and the ratio of type Ⅰ to Ⅲ collagen was calculated. At 30 d， relative expressions of MMP-1， MMP-3， MMP-9 and TIMP-1 in cardiac tissue were detected by Western blotting assay， and the ratio of MMPs to TIMPs was calculated. RESULTS： Compared with control group， mice in model group suffered from irritability， arch back， alleviation of stimulation response， reduction of body mass and even mental depression. Typical inflammatory changes and local interstitial hyperemia were observed in the myocardium， accompanied by a large number of lymphocyte infiltration and distribution of type Ⅰ and Ⅲ collagen. HW/BW （at different time points of 10-30 d）， myocardial histopathological score （at different time points of 4-30 d）， ratio of type Ⅰ and Ⅲ collagen （at different time points of 4-30 d）， the expression of MMP-1 and MMP-9， ratio of MMPs to TIMPs were increased significantly， while the expression of MMP-3 and TIMP-1 were decreased significantly （P＜0.05）. Compared with model group， above symptoms of mice in administration groups were improved to different extents. HW/BW [at different time points of 10-30 d in administration groups （except for 10 d in Buyang huanwu decoction low-dose group）]， myocardial histopathological score （at different time points of 10-30 d in administration groups）， ratio of type Ⅰand Ⅲ collagen （at different time points of 4-10 d in positive control group and Buyang huanwu decoction high-dose group， at different time points of 20-30 d in Buyang huanwu decoction low-dose and medium-dose groups）， the expression of MMP-1 （positive control group and Buyang huanwu decoction high-dose group） and MMP-9 （administration groups）， ratio of MMPs to TIMPs （administration groups） were decreased significantly， while the expression of MMP-3 （positive control group， Buyang huanwu decoction low-dose and high-dose groups） and TIMP-1 （administration groups） were increased significantly （P＜0.05）. CONCLUSIONS： Buyang huanwu decoction can inhibit myocardial fibrosis of VMC model mice by inhibiting myocardial collagen hyperplasia， regulating the expression of MMPs and TIMPs， improving MMPs/TIMPs imbalance.