Objective To discuss the influence of the management of family-doctor responsibility system on drug utilization and compliance of hypertensive patients.Methods 1039 primary hypertension patients in Zhenhai Lianhua Community who were under the management of the residents electronic health files in June 2012,were implemented with the latest family-doctor responsibility system for eight months.The on-site questionnaire survey and electronic health management platform were carried out to analyze the drug utilization and treatment compliance of hypertensive patients.Results The proportion of taking medicine treatment among 1039 patients with essential hypertension reached 85.2％,including 56.3％ patients who took one kind of drug,35.4％ patients who took two kinds of drugs and 8.3％ patients who took at least three kinds of drugs.The most commonly used drugs were Amlodipine Besylate,Felodipine,Irbesartan and Hydrochlorothiazide tablets,Irbesartan,Levamlodipine Besylate tablets,Metoprolol Tartrate tablets and etc.The rate of patient compliance was 65.5％.After comparing the compliance of any two among three kinds of drug groups,the comparison of compliance between patients who took one kind,two or three kinds of drugs showed statistical significance.The comparison of drug types and compliance showed that compliance with compound preparation was statistically different from compliance with ARB,calcium antagonists,sympatholytic agent,diuretics.The educational level was also related to the compliance.Conclusions After the implementation of the family-doctor responsible management,the treatment rate and compliance rate are high,and the patients with hypertension in community still give priority to long-acting drugs.

Objective To study the effect of Yuzhenxifeng Decoction on the brain ferritin in PD mouse models .Methods All ex‐perimental animals were devided into 4 groups:the control group ,the model group ,the positive drug group and TCM group .Prepare PD model mice with MPTP ,then use the immunohistochemical staining technique to observe the change of expression of Fn .Results the results showed that compared with the model group ,movement coordination disorder of rats in TCM group were relieved ;the Fn level of the model group on 6th ,13th ,20th were higher than control group(P<0 .05) ,and were 2 .21 times ,1 .15 times and 0 .36 times higher respectively .Compared with model group mice ,expression of Fn were enhanced in the treatment group .Conclusion Yuzhenxifeng Decoction can improve the expression of Fn in the brain ,which provide the basis for further study on mechanism of the treatment of Parkinson′s disease .

AIM: The cytoplasm Ca 2+, expression of Bcl-2 and Bax and germ cell apoptosis of testes in adult male rats with varicocele were observed to investigate the relationship between apoptosis and infertility. METHODS: Thirty-five healthy male Wistar rats were divided into two groups randomly: varicocele group (VG, n=20) and sham operation group (SOG, n=15). Bilateral testes were removed after ten weeks. One part of it was homogenized, the other part was performed for tissue sectioning. The atomic absorption method was used to detect the cytoplasm Ca 2+. The germ cell apoptosis was detected by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) technique. The expression of Bcl-2/Bax was detected by immunohistochemical method. RESULTS: The cytoplasm Ca 2+ in testes of rats with varicocele was decreased obviously. The apoptosis indexes of germ cells and Bax expression in VG were significantly increased as compared with those in the SOG, while Bcl-2 expression was obviously decreased. CONCLUSION: The results showed that apoptosis was increased in testes of VG rats, suggesting that male infertility with varicocele may be caused by some apoptosis agents such as high temperature, testes toxin and oxygen free radical. The cytoplasm Ca 2+ and change of expression of Bcl-2/Bax may contribute to germ cell apoptosis and cause male infertility.

AIM: To observe the effect of ischemic preconditioning on contents of cytochrome C and mitochondrial calcium in rats after focal cerebral ischemic-reperfusion. METHODS: Focal cerebral ischemic model was made by occlusion of right middle artery in Wistar rats (ischemia for 2 h and reperfusion for 4 h). Rats were randomly divided into three groups: ischemia pretreatment, model and sham operation. Rats in ischemic pretreatment group were undergone transient ischemic preconditioning (30 min) and reperfusion (72 h). The contents of cytochrome C were measured according to Zhangjuntian's improved methods. The contents of mitochondrial calcium were detected by flame atom absorption. RESULTS: The contents of mitochondrial cytochrome C and calcium in model group were significantly lower than those in sham operation (P

Breast Neoplasms ; genetics ; Carcinoma ; genetics ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Polymerase Chain Reaction ; methods ; Receptor, ErbB-2 ; genetics

OBJECTIVETo explore the mischief mechanism of oxidative stress in the varicocele (VC).

METHODSSerum was taken from the spermatic and peripheral veins on ligation of the internal spermatic veins in 28 infertile males with VC. Experimental VC was established in male rats by partial ligation of the left renal vein. And testis tissue was taken three months after operation. The nitric oxide(NO), nitric oxide synthetase (NOS), xanthine oxidase (XO), lactic acid(Lac) and lactic dehydrogenase (LDH) in the serum of 28 infertile males with VC and the testis tissue of the VC rats were detected by spectrophotometry.

RESULTSNO, NOS, XO and Lac in the serum of internal spermatic veins in the infertile males with VC were significantly higher than in the serum of peripheral veins in the VC patients (P < 0.01, P < 0.05). LDH was lower than that in peripheral serum. NO and XO of the left testis tissue in the VC rats were higher compared with the control group (P < 0.01). Lac in the left testis of the VC rats was lower than that in the control group rats (P < 0.01).

CONCLUSIONNO, NOS and XO in the serum of the VC patients and in the testis tissues of the VC rats were increased, and Lac and LDH were changed obviously, which might not only disturb spermatogenesis, but also inhibit sperm motility. Therefore they might be one of the causes of infertility in VC patients.

Adult ; Animals ; Humans ; Infertility, Male ; etiology ; Male ; Nitric Oxide ; analysis ; Nitric Oxide Synthase ; analysis ; Oxidative Stress ; Rats ; Rats, Wistar ; Varicocele ; complications ; metabolism ; Xanthine Oxidase ; analysis

Objectives: To compare the efficacy and safety of Chinese generic imatinib with branded imatinib as frontline therapy in adults with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) (Frontline group) , and to explore the efficacy and safety of Chinese generic imatinib in CML-CP patients switching from branded imatinib (Switching group) . Methods: Frontline group: Data of adults with newly diagnosed CML-CP receiving Chinese generic imatinib (Xinwei^®) or branded imatinib (Glivec^®) between October 2013 and August 2018 were retrospectively collected and analyzed. Switching group: Data of adults diagnosed with CML-CP who received branded imatinib and then switched to Chinese generic imatinib after achieving at least complete cytogenetic response (CCyR) were retrospectively collected and analyzed. Results: Frontline group: In total, 409 adult patients receiving Chinese generic imatinib (n=201) or Glivec (n=208) were included in this study. Median age was 42 years (range, 18-83 years) . Comparison of baseline showed significant difference on demographic characteristics among two cohorts: lower education level (P<0.001) , and divorced or widowed status (P=0.004) and rural household registration (P<0.001) were more common in the generic imatinib cohort than those in the Glivec cohort. There was no significant difference on age, gender, Sokal risk score, WBC and HGB between the 2 cohorts. With a median follow-up of 25 months (range, 3-62 months) , there was no significant difference on the 3-year cumulative incidence of achieving CCyR (97.5% vs 94.5%, P=0.592) , major molecular response (MMR) (84.3% vs 93.1%, P=0.208) , molecular response^4.0 (MR^4.0) (42.7% vs 41.7%, P=0.277) , molecular response^4.5 (MR^4.5) (25.4% vs 33.0%, P=0.306) as well as the 3-year probabilities of failure free survival (FFS) (76.7% vs 81.0%, P=0.448) , progression free survival (PFS) (91.8% vs 96.3%, P=0.325) and overall survival (OS) (95.8% vs 98.5%, P=0.167) between the generic and branded imatinib cohorts. Multivariate analysis showed the type of imatinib was not associated with treatment responses and outcomes. The incidences of adverse effects were comparable in the 2 cohorts. Switching group: In total, 39 patients switching from branded imatinib to Chinese generic imatinib after achieving at least CCyR were included in this study. Median age was 42 years (range, 23-80 years) . With a median follow-up of 39 months (range, 6-63 months) , molecular responses were maintained in 23 (58.9%) patients and improved in 12 (39.8%) patients. Adverse effects were tolerable. Conclusion Demographic characteristics might influence the choice of the type of TKI used in CML-CP patients. There was a comparable efficacy and safety between the Chinese generic imatinib and the branded imatinib in adults with newly diagnosed CML-CP under standard management and closely monitoring. Patients could safely switch from the branded imatinib to the Chinese generic imatinib.

Objective: To explore status of tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic myeloid leukemia (CML) in the chronic phase (CP) in the real world, to analyze causes, factors and outcomes associated with TKI discontinuation and the possibility of pursuit treatment-free remission (TFR) in China. Methods: From January 2013 to August 2016, data of CML-CP patients in Peking University People’s Hospital which were not enrolled in clinical trials were retrospectively collected and analyzed. Results: Data of 662 CML-CP patients were collected. With a median follow-up after TKI-therapy of 26 months (range, 3-187 months) , 187 patients (28.2%) experienced TKI cessation of at least 2 weeks. Causes of TKI discontinuation included hematologic adverse events 57.8% (n=108) , non-hematologic adverse events 30.4% (n=57) , financial burden 25.1% (n=47) , and others 7.0% (n= 13) . Multivariate analyses showed female, ≥40 years, no co-morbidity, and interval from diagnosis to TKI initiation ≥6 months, TKI switch and patients from other hospitals were factors associated with TKI discontinuation because of hematologic adverse effects. Female and patients from other hospitals were factors associated with TKI discontinuation because of non-hematologic adverse effect. TKI switch, generic TKI used and patients from other hospitals were factors associated with TKI discontinuation because of financial toxicity. Patients TKI discontinuation because of hematologic, non-hematologic or financial toxicity achieved a lower complete cytogenetic response or complete molecular response (CMR) than those with uninterrupted TKI-therapy. Patients with TKI discontinuation because of hematologic or financial toxicity had a shorter progression-free survival than those with uninterrupted TKI-therapy. 5 of 7 patients who obtained sustained CMR and discontinued TKI-therapy experienced disease recurrence with a median duration of 3 months (range, 2-32 months) . In 39 patients from other hospitals who aimed to confirm their optimal response of sustained CMR in Peking University People’s Hospital, 21 (53.8%) were BCR-ABL positive. Conclusion In the real world in China, half of CML-CP patients who discontinued TKI-therapy were incurred to TKI-related hematologic adverse effect, and both a quarter of them, TKI-related non-hematologic toxicities and financial toxicity, respectively. Discontinued TKI-therapy due to hematologic adverse events or financial toxicity was associated with lower TKI-therapy response rates. Nowadays, based on the Chinese situation, it is too early to talk about TFR.

Objectives: To explore the incidence and factors of severe leukopenia and/or thrombocytopenia in newly diagnosed patients with chronic myeloid leukemia (CML) to probe their impacts on cytogenetic and molecular responses, progression free survival (PFS) and overall survival (OS) . Methods: Data of newly diagnosed patients with CML in the chronic phase (CP) and/or accelerated phase (AP) were retrospectively collected and analyzed. Results: 855 CML patients [including 744 (87%) in the CP and 111 (13.0%) in the AP] were included in this study. 523 (61.2%) patients were male with a median age of 39 years (range, 14-87 years) . 749 (87.6%) patients received imatinib, 93 (10.9%) nilotinib, and 13 (1.5%) dasatinib, respectively as front-line therapy. At a median treatment of 1 month (range, 0.1-7.0 months) , 137 (16.0%) developed ≥grade 3 leukopenia and/or thrombocytopenia and recovered 0.6 month (range, 0.3-6.5 months) . Multivariate analysis showed that female gender (OR=1.5, 95%CI 1.0-2.2, P=0.033) , WBC ≥100×10⁹/L (OR=1.9, 95%CI 1.3-2.8, P=0.001) , CP in Sokal high-risk (OR=2.2, 95%CI 1.2-3.9, P=0.005) , AP with ≥15% blast cells in blood or bone marrow (OR=5.1, 95%CI 1.9-13.3, P=0.001) were factors associated with higher incidence of ≥grade 3 leukopenia and/or thrombocytopenia. Severe leukopenia and/or thrombocytopenia with time of drug discontinuance >2 weeks was associated with lower probabilities of achieving complete cytogenetic (OR=0.4, 95%CI 0.3-0.6, P<0.001) , severe leukopenia and/or thrombocytopenia, no matter the time of drug discontinuance >2 weeks or ≤2 weeks, were associated with lower probabilities of achieving major molecular responses (OR=0.3, 95%CI 0.2-0.5, P<0.001; OR=0.7, 95%CI 0.5-1.0, P=0.036) and MR4.5 (OR=0.2, 95%CI 0.1-0.5, P=0.002; OR=0.7, 95%CI 0.4-1.1, P=0.110) ; however, those had no impacts on PFS and OS. Conclusions Severe leukopenia and/or thrombocytopenia were common adverse events during TKI therapy. Female patients, WBC ≥100×10⁹/L at diagnosed, CP in Sokal high-risk, CML-AP with ≥15% blast cells in blood or bone marrow were at high risk for higher incidence of severe leukopenia and/or thrombocytopenia. Those severe adverse events had impacts on lower cytogenetic and molecular response.

Objective To investigate the impact of sample typeon the detection of c-KIT exon 17 mutation in acute myeloid leukemia (AML) patients. Methods A retrospective study was conducted on 51 bone marrow samples collected from 37 AML patients [17 maleand 20 female, with a median age of 33 (range from 1 to 82)] at diagnosis or after treatment from June 2016 to August 2018. Of the 37 cases of AML, 24 were t(8; 21) AML, 11 were inv(16)/t(16;16) AML and 2 were non-CBF-AML. RNA and DNA were simultaneously extracted from every sample. PCR followed by Sanger sequencing were used to screen c-KIT exon 17 mutation, and the comparisons were made between paired cDNA and DNAsamples. Results (1) Of the 51 paired samples, 14 pairs were simultaneously detected positive for c-KITmutation in both of cDNA and DNA samples, but 17 pairs were detected negative in both, and the remaining 20 pairswere only detected positive for the mutation in cDNA but not in DNA, with an inconsistency rate of 39.2％. The positive rate of detecting c-KITmutation was significantly higher in cDNA than in DNA samples (66.7％vs 27.5％,P=0.000073). (2)Inconsistent mutation results between paired cDNA and DNA samples occurred in t(8;21)AML, inv(16)AML and non-CBF-AML patients with the inconsistency rate of 36.4％(12/33), 27.2％(3/11) and 71.4％ (5/7), respectively. (3)The inconsistency rate was significantly higher in samples collected after treatment compared with those collected at diagnosis (72.7％vs 13.8％, P=0.00003). (4) All 5 serially monitored patients with c-KITmutation had inconsistency in mutation detection between cDNA and DNA samples during follow up. Conclusion cDNA improves the detection of c-KIT exon 17 mutation in AML patients compared with DNA, which is especially common after treatment.