Drug-coated balloon for in-stent restenosis in femoropopliteal segment: 1-year clinical outcomes from a multicenter study in China / 中华普通外科杂志

Objective:To evaluate the safety and efficacy at 1-year follow-up of the use of drug-coated balloon (DCB) for the treatment of femoropopliteal in-stent restenosis (ISR).Methods:This study enrolled 252 patients undergoing Orchid DCB angioplasty for peripheral arterial disease in the femoral-popliteal segment. The clinical data were retrospectively analyzed.Results:Forty-nine patients were eligible, including 29 (59.2%) chronic total occlusions belonging to TransAtlantic Inter-Society Consensus-Ⅱ(TASC Ⅱ) D, 7 (14.3%) thrombosis, and 14 (28.6%) moderate to severe calcifications. The mean lesion length was (215.9±97.1) mm. 69.4% were of occlusive lesions (Tosaka Ⅲ category). Only 1 provisional stent was implanted. 98% patients had severe claudication or even worse. Of these cases, 34 (73.9%) showed improvements in Rutherford category, while 11 (23.9%) did not change and 1 (2.2%) case deteriorated. The average value of ABI was 0.478±0.264 before surgery and 0.907±0.207 at the end of follow-up. The improvement in Rutherford category ( P<0.01) and ABI ( P<0.005) were both significant. The primary patency (PP) was 80.4%, and the freedom from clinically driven TLR was 84.8% at 1 year. During the follow-up period, there was no all-cause death and major limb amputation. Conclusion:This multicenter study demonstrated the effectiveness of DCB as a treatment for complicated and extensive ISR lesions within 12 months.

Advances and challenges in clinical research on hepatic hydrothorax / 临床肝胆病杂志

Hepatic hydrothorax (HH) is a challenging complication of liver cirrhosis associated with portal hypertension, and its pathogenesis and therapeutic measures remain unknown. This article summarizes and reviews the advances and challenges in the research on the pathogenesis, clinical manifestations, diagnosis, and treatment of HH and proposes a multidisciplinary treatment strategy, including reducing the production of ascites, preventing effusion from entering the thoracic cavity, removing pleural effusion, occluding the pleural cavity, and performing liver transplantation, so as to provide a reference for more clinicians.

Epidemiological analysis of incidence rate, surgical rate and spontaneous cure of indirect inguinal hernia in children of Xinjiang region / 中华消化外科杂志

Objective:To investigate the incidence rate, surgical rate and spontaneous cure of indirect inguinal hernia in children of Xinjiang region.Methods:Children, aged from 4?14 years, coming from 24 kindergartens, 18 primary schools and 9 junior middle schools of 3 countries and 5 cities in Xinjiang Uygur Autonomous Region were recruited to participate as respondents. The survey time for baseline data collection was from May 2013 to June 2014 and the retrospective cross-sectional survey was conducted. Parents of children were investigated by questionnaire, and children were examined on site. Observation indicators: (1) results of questionnaire survey; (2) illness and treatment of children involved in the study; (3) follow-up. Follow-up was conducted using telephone interview. Children who had been diagnosed and not been treated surgically at the time of questionnaire survey were followed up to detect disease progression and treatment in the past 5 years. If the symptoms of a child had disappeared during follow-up, parents of the child should accompany the child to hospital for physical examination and B-ultrasound examination to confirm the diagnosis, and then follow-up was conducted by telephone interview. The follow-up was up to January 2020. Count data were described as absolute numbers and percentages, and compari-son between groups was conducted using the chi-square test. Odds ratio and 95% confidence interval were calculated. Results:(1) Results of questionnaire survey. A total of 19 132 question-naires were distributed, and 19 132 complete questionnaires were recovered. Of the 19 132 children who completed the questionnaire survey, there were 9 670 males and 9 462 females. (2) Illness and treatment of children involved in the study. ① Incidence of indirect inguinal hernia in children with different sexes. Of the 19 132 children, 498 cases were diagnosed as indirect inguinal hernia, including 368 boys and 130 girls, with the prevalence as 3.806%(368/9 670) and 1.374%(130/9 462), respectively. There was a significant difference in the prevalence of indirect inguinal hernia between boys and girls ( χ2=111.54, P<0.05). The proportion of boys and girls in children with indirect inguinal hernia was 73.896%(368/498) and 26.104%(130/498), respectively, with the ratio of 2.8:1. The prevalence of boys was higher than girls ( odds ratio=2.84, 95% confidence interval as 2.32?3.48).② Age of children at first onset. Of the 498 children with indirect inguinal hernia, 59 cases were aged 1?4 years at first onset including 54 boys and 5 girls, 264 cases were aged 5?8 years including 196 boys and 68 girls, 148 cases were aged 9?12 years including 104 boys and 44 girls, 27 cases were aged 13?14 years including 14 boys and 13 girls. There was a significant difference in the age of children at first onset between boys and girls ( χ2=17.33, P<0.05). ③ Pathogenic factors in children with indirect inguinal hernia. Of the 498 children with indirect inguinal hernia, 457 cases had complete family history and crying history, and 41 cases were missing. Family history: of the 457 children with indirect inguinal hernia who had complete family history, there were 175 cases with the family history of indirect inguinal hernia and 282 cases without the family history. Of the 478 healthy children surveyed in the same period, there were 25 cases with the family history and 453 cases without the family history. There was a significant difference in the family history between the 457 children with indirect inguinal hernia and the 478 healthy children ( χ2=515.89, P<0.05). Crying history: of the 457 children with indirect inguinal hernia who had complete crying history, there were 194 cases with obvious crying history and 263 cases without obvious crying history. Of the 496 healthy children surveyed in the same period, there were 99 cases with obvious crying history and 397 cases without obvious crying history. There was a significant difference in the crying history between the 457 children with indirect inguinal hernia and the 496 healthy children ( χ2=56.51, P<0.05). ④ Surgical treatment. Of the 498 children with indirect inguinal hernia, 233 cases underwent surgical treatment including 217 boys and 16 girls, 265 cases were followed up without surgical treatment including 151 boys and 114 girls. The surgical rate for indirect inguinal hernia in boys and girls was 58.967%(217/368) and 12.308%(16/130), respectively, showing a significant difference between them ( χ2=84.01, P<0.05). The operation ratio of boys and girls was 13.6:1, and the surgical rate of boys was higher than girls ( odds ratio=10.24, 95% confidence interval as 5.83?17.98). (3) Follow-up. All the 265 children without surgical treatment for indirect inguinal hernia were followed up for 5 years. During the follow-up, there were 142 of 151 boys with surgical treatment and 9 boys without surgical treatments, showing negative in spontaneous cure. There were 27 of 114 girls with surgical treatment and 87 girls without surgical treatment, showing 55 cases positive in spontaneous cure and 32 cases still with indirect inguinal hernia. There was a significant difference in spontaneous cure between the 151 boys and the 114 girls ( χ2=143.79, P<0.05). Conclusion:In Xinjiang region, the incidence rate and surgical rate of indirect inguinal hernia are lower in girls compared with boys, and the spontaneous cure rate is higher in girls compared with boys.

Application of lymphocytes test in peripheral blood of patients with systemic sclerosis during the treatment / 北京大学学报(医学版)

OBJECTIVE@#To explore the significance of lymphocytes in systemic sclerosis (SSc), by detecting the levels of T lymphocytes, B lymphocytes and natural killer (NK) cells, and analyzing the correlation between the lymphocytes and clinical laboratory indexes.@*METHODS@#The numbers and proportion of T, CD4+T, CD8+T, B, and NK cells were detected by flow cytometry in peripheral blood of 32 SSc patients who had taken immunosuppressive drugs and 30 healthy controls (HC). The comparison of the lymphocyte subsets in SSc with them in the HC groups, and the correlation between the lymphocytes and other clinical and laboratory indicators were analyzed by the relevant statistical analysis.@*RESULTS@#Compared with the HC group, the numbers of T, CD4+T, CD8+T, and NK cells in peripheral blood of SSc group, who had taken immunosuppressive drugs, were significantly decreased (P < 0.05). More-over, the proportion of NK cells in peripheral blood of the SSc group was also significantly lower than that in the HC group (P=0.004). In addition, all the lymphocyte subsets were decreased in peripheral blood of more than 65% of the SSc patients who had taken immunosuppressive drugs. Compared with CD4+T normal group, the positivity of Raynaud's phenomenon, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) was significantly increased in CD4+T reduction group, respectively (P＝0.024, P < 0.001, P=0.018). ESR was higher in CD8+T reduction group than CD8+T normal group (P＝0.022). The prevalence of fingertip ulcer was significantly increased in B cell decrease group (P=0.019). Compared with NK cell normal group, the prevalence of fingertip ulcer was significantly increased in NK cell lower group (P=0.033), IgM was remarkablely decreased yet (P=0.049). The correlation analysis showed that ESR was negatively correlated with the counts of T lymphocytes (r＝－0.455, P＝0.009), CD4+T lymphocytes (r＝－0.416, P＝0.018), CD8+T lymphocytes (r＝－0.430, P=0.014), B cells (r＝－0.366, P＝0.039).@*CONCLUSION@#The number of CD4+T, CD8+T, B, and NK cells significantly decreased in peripheral blood of SSc patients who had used immunosuppressive drugs, some lymphocyte subsets might be related with Raynaud's phenomenon and fingertip ulcer, and reflected the disease activity by negatively correlated with ESR and CRP; the numbers of lymphocyte subsets in peripheral blood should be detected regularly in SSc patients who had taken immunosuppressive drugs.

Research advances in primary biliary cholangitis with hyperlipidemia / 临床肝胆病杂志

Dyslipidemia is one of the most common complications of primary biliary cholangitis (PBC). This article reviews the latest research on lipid profile, the risk of cardiovascular diseases, and treatment of PBC with hyperlipidemia. Different from other liver diseases, PBC with hyperlipidemia has a unique lipid profile, which changes dynamically with disease progression. It is generally not considered that there are increased risks of atherosclerosis and cardiovascular disease. For those who have indications for treatment, statins are recommended as the first choice. In the future, more in-depth systematic studies are needed to clarify its diagnosis, treatment, and management processes.

Serum proteomic approach in patients with Qi deficiency and blood stasis syndrome in coronary heart disease:to explore therapeutic mechanism of Yiqi Huoxue decoction / 中国药理学与毒理学杂志

OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome. METHODS The patients with coronary heart dis?ease of Qi deficiency and blood stasis syndrome were treated with Yiqi Huoxue decoction for 3 months, and the changes of cardiac function were observed. 61 serum samples (including 29 cases of disease group and 32 cases of Yiqi Huoxue expression group) were analyzed by non labeled proteomics. The disease group was used as the control group, and the protein with expression level difference of more than 1.2 folds (P<0.05) was screened. The molecular function, biologi?cal pathway and protein interaction of the different proteins were analyzed by bioinformatics, so as to identify the molecu?lar and biological pathway of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome. RESULTS Clinical treatment found that Yiqi Huoxue decoction can improve TCM syndrome score and left ventricular ejection fraction, regulate blood glucose and blood lipid levels, prolong thrombin time, and improve heart function. The results of proteomic quantitative analysis showed that there were 69 proteins with different expression levels in the disease group. Bioinformatics analysis results showed that Yiqi Huoxue decoction may regulate ApoA1, alpha-2 and other proteins to act on HDL assembly, platelet degradation, PI3K Akt signaling pathway, and then play a therapeutic role in coronary heart disease with Qi deficiency and blood stasis syndrome. CONCLUSION Yiqi Huoxue decoction can effectively improved the heart function decline caused by Qi deficiency and blood stasis syn?drome of coronary heart disease. It mainly act on energy metabolism and platelet activation pathway by activating HDL assembly and platelet degradation signal pathway proteins. This study can provide reference for the follow-up treatment mechanism of Qi deficiency and blood stasis syndrome of coronary heart disease.

The whole process management principles of chimeric antigen receptor T-cell therapy for lymphoma at Peking University Cancer Hospital / 白血病·淋巴瘤

Chimeric antigen receptor T (CAR-T) cell has achieved excellent efficacy in hematological tumors, especially for lymphoma. Many products have been approved to market all over the world, and 2 products targeting CD19 have been approved to treat relapsed and refractory large B-cell lymphoma in China. The current experiences of using CAR-T cells come from previous clinical studies. How to use CAR-T cells in a standardized and rationalized way is still a challenge faced by our clinicians. Based on the CAR-T cell treatment experiences from Peking University Cancer Hospital and the latest research progresses in CAR-T in China and abroad, this article will elaborate on patient screening, peripheral blood mononuclear cell collection, bridging treatment, lymphocyte depletion chemotherapy, CAR-T cell infusion, the monitoring and treatment of adverse events after infusion, and long-term follow-up after infusion, in order to guide clinicians to better use CAR-T cell and to bring maximum benefits to patients.

Efficacy of Modified Huanglian Wendantang and Shaofu Zhuyutang Against Ovulation Disorder in Combined Phlegm and Stasis-Induced Polycystic Ovary Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Huanglian Wendantang and Shaofu Zhuyutang in the treatment of ovulation disorder in patients with polycystic ovary syndrome （PCOS） due to the combined phlegm and stasis-induced and its influence on chronic inflammation. Method:According to the random number table， 100 patients were divided into a control group （50 cases） and an observation group （50 cases）. Apart from lifestyle intervention and oral administration of clomiphene citrate （CC） capsules to induce ovulation， patients in the control group further received Guizhi Fulingwan， 6 g/time， 2 times/day， while those in the observation group were treated with the modified Huanglian Wendantang and Shaofu Zhuyutang， 1 dose/day， for six menstrual cycles. The ovulation， endometrial thickness， proportion of type A endometrium， as well as the pulsatility index （PI） and resistance index （RI） of uterine artery were monitored before and after treatment. The fasting blood glucose （FBG）， fasting insulin （FINS）， luteinizing hormone （LH）， follicle stimulating hormone （FSH）， serum testosterone （T）， estradiol （E₂）， dehydroepiandrosterone sulfate （DHEAS）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， high-sensitivity C-reactive protein （hs-CRP）， adiponectin （APN）， and interleukin-6 （IL-6） levels before and after treatment were detected， followed by the calculation of homeostasis model assessment-insulin resistance （HOMA-IR） value and the evaluation of ovarian volume and combined phlegm and stasis-induced syndrome score. Result:The overall response rate of the observation group was （44/47） 93.62%， which was higher than （36/46） 78.26% of the control group （<italic>χ</italic>²=4.802， <italic>P</italic><0.05）. The ovulation rate in the observation group was （199/264） 75.38%， higher than （173/272） 63.60% in the control group （<italic>χ</italic>²=8.714， <italic>P</italic><0.01）. The clinical pregnancy rate of the observation group was （11/47） 23.40%， higher than （5/46） 10.87% of the control group， but the difference was not statistically significant （<italic>χ</italic>²=2.564， <italic>P</italic>>0.05）. Compared with the control group， the observation group exhibited reduced PI， RI， LH， T， DHEAS， FINS， FPG， HOMA-IR， TNF-<italic>α</italic>， hs-CRP， and IL-6 （<italic>P</italic><0.01）， but elevated E₂， FSH， and APN （<italic>P</italic><0.01）. Besides， the bilateral ovarian volume and combined phlegm and stasis-induced syndrome score of the observation group were smaller than those of the control group （<italic>P</italic><0.01）， while the endometrial thickness and proportion of type A endometrium were higher （<italic>P</italic><0.01）. Conclusion:On the basis of CC treatment， the modified Huanglian Wendantang and Shaofu Zhuyutang alleviates the ovulation disorder in PCOS patients of combined phlegm and stasis-induced syndrome and regulates IR and chronic inflammation， thus creating a favorable condition for clinical pregnancy， which is worthy of further research.

Modified Xiaoyao Erxian Decoction in Treatment of Mood Disorders in Perimenopausal Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Xiaoyao Erxian decoction in the treatment of mood disorders among perimenopausal syndrome due to kidney deficiency and liver depression and its effects on monoamine neurotransmitters and brain-derived neurotrophic factor （BDNF）. Method:According to the random number table， 108 patients were divided into a control group （54 cases） and an observation group （54 cases）. Control group were treated with Shugan Jieyu capsule orally， two capsules per time， two times per day， while those in the observation group received the modified Xiaoyao Erxian decoction， one bag per day， for 12 consecutive weeks. Before and after treatment， the Hamilton Anxiety Scale （HAMA）， 17-item Hamilton Depression Rating Scale （HAMD-17）， modified Kupperman Index （KI）， Pittsburgh Sleep Quality Index （PSQI）， Menopause-specific Quality of Life （MENQOL） and kidney deficiency and liver depression syndrome scores were calculated. The levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， BDNF， 5-hydroxytryptamine （5-HT）， norepinephrine （NE）， and dopamine （DA） were detected， followed by safety evaluation. Result:The HAMA， HAMD-17， KI， kidney deficiency and liver depression syndrome， PSQI， and MENQOL scores of the observation group were lower than those of the control group （<italic>P</italic><0.01）， whereas the 5-HT， E₂， DA， NE， and BDNF levels in the observation group were higher （<italic>P</italic><0.01）. The clinical efficacy of the observation group was superior to that in the control group （<italic>Z</italic>=2.184， <italic>P</italic><0.05）. No adverse reactions occurred after the oral administration of Chinese medicinal preparations. Conclusion:The modified Xiaoyao Erxian decoction effectively alleviates the mood disorders and other related symptoms of perimenopausal syndrome due to kidney deficiency and liver depression by regulating the monoamine neurotransmitters， BDNF， and E₂， without inducing obvious side effects.

Integrative analysis of prognostic long non-coding RNAs with copy number variation in bladder cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely

Establishment and gene expression analysis of drug-resistant cell lines in hepatocellular carcinoma induced by sorafenib / 北京大学学报(医学版)

OBJECTIVE@#To establish the drug-resistant cell lines of hepatocellular carcinoma (HCC) induced by sorafenib, and to screen out the high expression genes in drug-resistant cell lines of HCC induced by sorafenib, then to explore the genes related to sorafenib resistance in hepatocellular carcinoma.@*METHODS@#The human PLC and Huh7 cell lines were obtained, then the PLC and Huh7 drug-resistant cell lines were induced with sorafenib by using intermittent induction in vitro. CCK8 assay was used to detect the IC50 value of sorafenib for evaluation of drug sensitivity of hepatocellular carcinoma cell lines in PLC and Huh7. All the up regulated genes in PLC and Huh7 drug-resistant cell lines induced by sorafenib were screened out using high-throughput cDNA sequencing (RNA-Seq), Ualcan database was used to analyze the correlations between the up regulated genes in PLC and Huh7 drug-resistant cell lines induced and four clinical biological characteristics of hepatocellular carcinoma, including the gene expressions between normal samples and tumor samples, tumor stage, tumor grade, and patient overall survival, to find the genes that might be involved in the mechanism of sorafenib resistance of hepatocellular carcinoma.@*RESULTS@#All the up regulated genes detected by the using high-throughput cDNA sequencing (RNA-Seq) in PLC and Huh7 drug-resistant cell lines were further screened out by following conditions:(1) genes co-expressed in PLC and Huh7 drug-resistant cells induced by sorafenib, (2) the fold change was more than 4 times and the difference was statistically significant (P <0.05), the top 12 up regulated genes in PLC and Huh7 drug-resistant cell lines were found, which were TPSG1, CBX4, CLC, CLEC18C, LGI4, F2RL1, S100A6, HABP2, C15ORF48, ZG16, FOLH1, and EPCAM. Compared with the correlations between the twelve genes and the clinical biological characteristics by Ualcan database, the potentially significant gene CBX4 was screened out.@*CONCLUSION@#The human PLC and Huh7 drug-resistant cell lines of hepatocellular carcinoma induced by sorafenib were successfully established. CBX4, the gene related to sorafenib resistance in hepatocellular carcinoma, was screened out by the high-throughput cDNA sequencing (RNA-Seq) and further analysis using Ualcan database, which is providing a powerful basis for further research on the mechanism of sorafenib resistance of hepatocellular carcinoma.

Evaluation of the effect of the integrated echinococcosis control program in Ningxia Hui Autonomous Region from 2011 to 2018 / 中国血吸虫病防治杂志

ObjectiveTo evaluate the effect of the integrated echinococcosis control program in Ningxia Hui Autonomous Region from 2011 to 2018. MethodsA package of integrated interventions were employed for echinococcosis control in 22 counties (districts) of Ningxia Hui Autonomous Region from 2011 to 2018, including screening of human echinococcosis, treatment of echinococcosis patients, deworming of domestic dogs and monitoring of infections, surveillance of echinococcosis in bovines and sheep, health education. The detection of human echinococcosis, seroprevalence of anti-Echinococcus antibody in children at ages of 6 to 12 years, the Echinococcus coproantigen-positive rate in domestic dogs, prevalence of echinococcosis in bovines and sheep, and the awareness of echinococcosis control knowledge were investigated and compared during the period between 2011 and 2018. Results The detection of human echinococcosis appeared a decline tendency in Ningxia Hui Autonomous Region over years during the period from 2011 to 2018 (χ2trend = 82.22, P < 0.05), and the prevalence of human echinococcosis decreased from 0.31% in 2011 to 0.15% in 2018. The seroprevalence of anti-Echinococcus antibody appeared a decline tendency in children at ages of 6 to 12 years over years (χ2trend = 439.64, P < 0.01), and the prevalence of anti-Echinococcus antibody decreased from 6.12% in 2011 to 0.67% in 2018. The Echinococcus coproantigen-positive rate appeared a decline tendency in domestic dogs over years (χ2trend = 260.33, P < 0.05), and the prevalence of anti-Echinococcus antibody decreased from 7.11% in 2011 to 0.75% in 2018. The prevalence of bovine and sheep echinococcosis reduced from 3.26% and 5.08% in 2011 to 1.35% and 0.76% in 2018, and Echinococcus predominantly parasitized in bovine (92.00%) and sheep (93.94%) livers. A total of 63 stool samples were collected from red fox, wolf and badger in Xiji and Haiyuan counties of Ningxia Hui Autonomous Region in 2013 and 2014, with no Echinococcus coproantigen-positives detected, and 107 domestic cats and 3 domestic dogs were dissected in these two counties, with no Echinococcus found. A total of 6 046 wild mice were dissected in Xiji County, Yuanzhou District and Haiyuan County of Ningxia Hui Autonomous Region from 2016 to 2019, and the prevalence of E. multilocularis was 0.31%. The awareness of echinococcosis control knowledge appeared an increasing tendency in Ningxia Hui Autonomous Region over years from 2011 to 2018 (χ2trend = 3 367.97, P < 0.01), and the awareness increased from 21.83% in 2011 to 72.24% in 2018. Conclusions The integrated echinococcosis control program achieves a remarkable effect in Ningxia Hui Autonomous Region, and the transmission of echinococcosis has been preliminarily controlled. However, the echinococcosis transmission risk remains in few regions, and the integrated echinococcosis control program remains to be reinforced.

Preliminary evaluation of adjuvant effects of cyclic dinucleotides ( CDN ) on immune responses to nasal spray influenza vaccine / 中华微生物学和免疫学杂志

Objective To analyze the immunostimulatory effects of cyclic dinucleotides ( CDN) on immune responses to a nasal spray influenza split virus vaccine and to evaluate its potential as a mucosal ad-juvant. Methods A H1N1 influenza split virus vaccine combined with different CDN was used for mouse immunization. Each mouse was intranasally immunized twice with 4. 5μg of hemagglutinin (HA) and 10μg of CDN with an interval of 21 d. Titers of hemagglutination inhibition ( HI) antibodies in serum, secretory IgA ( sIgA) in bronchoalveolar lavage fluid and IgG in serum were detected 21 d after the last immunization. Immunostimulatory activities of different CDN were compared. Effects of cyclic di-GMP ( c-di-GMP) and ch-itosan (CSN) on the immunogenicity of H1N1 and H7N9 influenza split vaccines were analyzed and com-pared. H1N1 influenza split vaccine combined with c-di-GMP or CSN was used to immunize mice. Three weeks after the last immunization, these mice were challenged with 10 times the median lethal dose ( LD50 ) of A/Puerto Rico/8/34 (H1N1) influenza virus. Survival rates of the mice were observed for 14 d. Results All three CDN induced high levels of HI antibodies and IgG in serum and sIgA in BALF. HI antibody sero-conversion rates were also higher than those of the control groups. c-di-GMP was superior to CSN in enhan-cing the immunogenicity of H1N1 and H7N9 antigens as higher titers of HI antibodies in serum and sIgA in BALF were induced. Conclusions CDN could enhance the immunogenicity of influenza antigens with better efficacy than CSN adjuvant.

Yiqi Tongluo Particles improve Qi-deficiency and blood stasis in multiple cerebral infarction rats by promoting angiogenesis / 中国中药杂志

This research was aimed to evaluate the protective effect and potential mechanism of Yiqi Tongluo Particles(YQTLs).Firstly,an animal model of multiple cerebral infarction(MCI) with Qi deficiency and blood stasis was established.Rats were randomly divided into six groups:SHAM group,Vehicle group,Buyang Huanwu decoction original group(BYHWO),EGb761 group,high and low dose of YQTLs group.Rats underwent sleep deprivation after one week of MCI and the tongues and pulses of rats after six weeks of sleep deprivation were detected,followed by collecting blood to analysis the blood coagulation.Differential expression of angiogenesis associated proteins was examined using proteomic research and verified by immunohistochemical.RESULTS: showed that neurological function score was obviously declined,G and B value of tongue surface was increased significantly and the pulse distension,the activated partial thromboplatin time(APTT) as well as prothrombin time(PT) were recovered following YQTLs 7.56 g·kg-1 treatment.Furthermore,G value of tongue surface,APTT and PT were also improved by YQTLs 3.78 g·kg-1.The results of proteomic technology showed that proteins associated with angiogenesis were reversed compared with Vehicle group.Moreover,the expression of VEGFR2 from immunohistochemical was promoted after YQTLs treatment.The MCI with Qi deficiency and blood stasis was alleviated obviously following YQTLs treatment and the possible mechanism was that YQTLs may enhance angiogenesis during cerebral ischemia.

Brucine in inducing cell apoptosis of human pancreatic cancer CFPAC-1 cells by regulating the pathway of mitochondrial apoptosis / 中华胰腺病杂志

Objective@#To investigate the influence of Brucine on cell apoptosis of pancreatic cancer CFPAC-1 cells and the possible mechanism.@*Methods@#Brucine in different concentrations were used to treat CFPAC-1 cells. Cell proliferation was determined by MTT assay and cell apoptosis was determined by flow cytometer assay. Mitochondrial membrane potential was examined by JC-1 staining. The protein expression of Bax and Bcl-2 was measured by Western Blot.@*Results@#The growth inhibition rates of CFPAC-1 cells after being treated with 0 (control group), 0.4 and 0.8 mmol/L Brucine for 24, 48 and 72 h were 0, (30.23±0.55)%, (40.61±0.15)%, (46.98±1.27)% and(50.17±0.75)%, (61.23±0.91)%, (70.32±0.40)%, increasing with a concentration- and time-dependent increase, which was higher than that in control group; and the differences between either two groups at different time points were statistically significant (P<0.05). CFPAC-1 cell apoptosis rate after being treated with 0, 0.4 and 0.8 mmol/L Brucine for 48 h was (2.92±0.46)%, (4.64±1.31)% and (13.09±0.65)%, which increased gradually with the increased drug concentration. The apoptotic rate in 0.8 mmol/L treatment group was obviously higher than that in control group, and the difference was statistically significant (P<0.05). With the increase of the drug concentration, the red fluorescence gradually decreased, and the green fluorescence gradually increased, indicating that the mitochondrial membrane potential was severely damaged and thus decreased. The protein expression of Bcl-2 in CFPAC-1 cells were(0.92±0.12), (0.67±0.14)and(0.35±0.14)mmol/L, and the expression of Bax in CFPAC-1 cells were(0.56±0.12), (0.85±0.10)and(1.15±0.12)mmol/L. With the increase of brucine concentration, the expression of Bcl-2 was significantly reduced while the expression of Bax was significantly increased; and the difference was statistically significant (P<0.05).@*Conclusions@#Brucine can effectively induce the apoptosis of human pancreatic cancer CFPAC-1 cells through mitochondrial apoptotic pathway by up-regulating the expression of Bax and down-regulating the expression of Bcl-2.

Effect of Method of Regulating Qi to Dissipate Blood Stasis and Phlegm on Cardiac Rehabilitation in Patients with Qi Deficiency and Blood Stasis Type Chronic Heart Failure / 中国实验方剂学杂志

Objective: To observe effect of method of regulating Qi to dissipate blood stasis and phlegm on degree of heart failure, ventricular remodeling, disease progression in patients with Qi deficiency and blood stasis type chronic heart failure (CHF).Method: One hundred and thirty-four patients with CHF were randomly divided into control group (62 cases) and observation group (62 cases) by random number table. The patients in control group got spironolactone tablets, 20 mg/time and qd. Benazepril, 20 mg/time and qd. Bisoprolol, 10 mg/time and qd. And digaoxin tablets if necessary. Based on the treatment in control group, patients in observation group additionally received Danshenyin and Xuefu Zhuyutang, 1 dose/day. The treatment course was 3 months in both groups. Before and after treatment, scores of Lee heart failure score were graded, cardiac function classification of the New York Heart Association (NYHA), 6 mins' walking test (6 MWT), scores of Qi deficiency and blood stasis and Minnesota living with heart failure questionnaire (MLHFQ) were evaluated. Echocardiography, left ventricular ejection fraction (LVEF), Left ventricular end-diastolic diameter (LVEDd), left ventricular end-stolic diameter (LVEDs), interventricular septum thickness at end-diastole (IVSd) and left ventricular myocardial mass index (LVMI) were recorded. Levels of matrix metalloprotein-9 (MMP-9), tissue inhibitor of matrix metalloprotease-1 (TIMP-1), transforming growth factor-β1 (TGF-β1), N-terminal pro-B-type na-triuretic peptide (NT-proBNP), galectin-3 and copeptin were detected.Result: Ridit analysis showed that after treatment, effect on cardiac function in observation group was better than that in control group (PPPPPβ1, NT-proBNP, galectin-3 and copeptin in observation group were lower than those in control group, while level of TIMP-1 was higher than that in control group (PConclusion: Based on the routine western medicine treatment, additional Danshenyin and Xuefu Zhuyutang can ameliorate symptoms of heart failure, relieve degree of heart failure, improve exercise tolerance and quality of life, inhibit ventricular remodeling, improve cardiac rehabilitation and delay progress of the disease for the CHF patients with Qi deficiency and blood stasis.

Brucine in inducing cell apoptosis of human pancreatic cancer CFPAC-1 cells by regulating the pathway of mitochondrial apoptosis / 中华胰腺病杂志

Objective To investigate the influence of Brucine on cell apoptosis of pancreatic cancer CFPAC-1 cells and the possible mechanism. Methods Brucine in different concentrations were used to treat CFPAC-1 cells. Cell proliferation was determined by MTT assay and cell apoptosis was determined by flow cytometer assay. Mitochondrial membrane potential was examined by JC-1 staining. The protein expression of Bax and Bcl-2 was measured by Western Blot. Results The growth inhibition rates of CFPAC-1 cells after being treated with 0 (control group), 0. 4 and 0. 8 mmol/L Brucine for 24, 48 and 72 h were 0,(30. 23 ± 0. 55)％,( 40. 61 ± 0. 15 )％, ( 46. 98 ± 1. 27 )％ and ( 50. 17 ± 0. 75 )％, ( 61. 23 ± 0. 91 )％, ( 70. 32 ± 0. 40)％, increasing with a concentration-and time-dependent increase, which was higher than that in control group; and the differences between either two groups at different time points were statistically significant (P<0. 05). CFPAC-1 cell apoptosis rate after being treated with 0, 0. 4 and 0. 8 mmol/L Brucine for 48 h was ( 2. 92 ± 0. 46 )％, ( 4. 64 ± 1. 31 )％ and ( 13. 09 ± 0. 65 )％, which increased gradually with the increased drug concentration. The apoptotic rate in 0. 8 mmol/L treatment group was obviously higher than that in control group, and the difference was statistically significant (P<0.05). With the increase of the drug concentration, the red fluorescence gradually decreased, and the green fluorescence gradually increased, indicating that the mitochondrial membrane potential was severely damaged and thus decreased. The protein expression of Bcl-2 in CFPAC-1 cells were(0.92 ±0.12),(0.67 ±0.14)and(0.35 ±0.14)mmol/L,and the expression of Bax in CFPAC-1 cells were(0. 56 ± 0. 12),(0. 85 ± 0. 10)and(1. 15 ± 0. 12)mmol/L. With the increase of brucine concentration, the expression of Bcl-2 was significantly reduced while the expression of Bax was significantly increased;and the difference was statistically significant (P<0. 05). Conclusions Brucine can effectively induce the apoptosis of human pancreatic cancer CFPAC-1 cells through mitochondrial apoptotic pathway by up-regulating the expression of Bax and down-regulating the expression of Bcl-2.

Qualitative and quantitative analysis of related substances in clotrimazole cream / 药学学报

For qualitative and quantitative analysis of related substances in clotrimazole cream, HPLC-Q-TOF spectrometer was used to analyze the fragmentation pathways and identify structures of the related substances. Five related substances named by BP (2018) were identified as impurity A ((2-chlorophenyl)-diphenylmethanol), impurity B (para-clotrimazole isomer), impurity E (2-chlorobenzophenone), impurity F (1-tritylimidazole) and impurity 4 (9-(2-chlorophenyl)-fluorene), respectively, by using impurity references matching and comparison with the literature data. Four related substances were detected in clotrimazole cream except impurity E, and 9-(2-chlorophenyl)-fluorene is the first identified impurity in this preparation. To establish an HPLC method for determination of the related substances in Clotrimazole Cream, the Agilent Poroshell Bonuns RP column was used (100 mm×4.6 mm, 2.7 μm) with UV detection at 215 nm. The mobile phase was acetonitrile-10 mmol·L-1 dipotassium phosphate buffer (adjusted with phosphoric acid to pH of 5.80) with a flow rate of 1.0 mL·min-1. Gradient elution was used. The column temperature was maintained at 40℃. A good linear behavior was achieved between component's concentrations and peak area for impurity A, B, E, F within the range of 0.20-10.02 μg·mL-1, 0.20-10.00 μg·mL-1, 0.20-10.10 μg·mL-1, 0.10-5.01 μg·mL-1 with the correlation coefficients were 0.999 7, 1.000 0, 1.000 0, 0.999 9, respectively. The average recoveries were 94.3%, 95.0%, 100.0%, 99.6% with RSDs were 2.8%, 2.2%, 1.1%, 2.7%, respectively (n=9). LOQ were 200.4, 200.0, 202.0, 100.2 ng·mL-1, respectively. LOD were 57.25, 57.14, 57.71, 28.63 ng·mL-1, respectively. The developed method was simple, rapid, accurate and effective for testing related substances in clotrimazole cream to control its quality, ensuring the safety of clinical medication.

Diagnosis and treatment of free floating thrombus in carotid artery / 中华普通外科杂志

Objective To evaluate diagnostic method and treatment strategy for free floating thrombus in carotid artery.Methods From Ju12016 to Oct 2017,7 patients with free floating thrombus in carotid artery was diagnosed at our department.The medical history,symptoms,diagnosis,treatment strategy and prognosis of those patients were analyzed retrospectively.Results Among 7 patients,4 were symptomatic;4 patients were concomitant with severe carotid artery stenosis and 3 with mild to moderate stenosis.3 received carotid endarterectomy and patch angioplasty.4 received carotid artery stenting with distal cerebral protection divice.There was no perioperative and 30-day stroke,myocardial infarction,death or hyperperfusion syndrome occurred.The 12-month follow up showed no restenosis,no free floating thrombus recurrence and no ischemic cerebrovascular event.Conclusion Free floating filling defect in carotid artery is a typical sign for unstable plaque.Both carotid endarterectomy and carotid artery stenting can be used for the treatment of free floating thrombus.

Progression of left ventricular hypertrophy in maintenance hemodialysis patients and analysis of risk factors / 上海交通大学学报（医学版）

Objective· To observe the progression of left ventricular hypertrophy (LVH) in maintenance hemodialysis (MHD) patients,and to analyse risk factors of the progression of LVH.Methods· Stable MHD patients of Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were enrolled in July 2012.These patients were followed for 1 year.Clinical characteristics and laboratory indices were collected at baseline and 1-year followup.Left ventricular mass (LVM) was evaluated by ultrasonic cardiogram.Left ventricular mass index (LVMI) increased more than 5％ was defined as LVH progression.Results · Totally 71 MHD patients were enrolled in this study.44 patients were males,with median age 55.9 years old,median dialysis vintage 152.1 months.22 (30.99％) patients had LVH at enrollment.A significant higher percentage of MHD patients used calcium-channel binder (CCB) and angiotensin-converting-enzyme inhibitor (ACEI) in LVH group,while a significant higher NT-proBNP level was also showed in LVH group.31 patients had LVH progression while 40 patients didn't after 1 year.Patients in progression group had significant higher levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C).In univariable and multivariable Logistic regression,total cholesterol and LDL-C were independent risk factors of LVH progression (OR=2.515,95％ CI 1.219-5.910,P=0.013;OR=1.950,95％ CI 1.127-3.375,P=0.017).Conclusion · LVH is one of the common cardiovascular complications in MHD patients.The proportion of use of antihypertensive drugs is higher in the patients with LVH.Higher LDL-C and total cholesterol levels are risk factors for the progression of LVH.