Objective:To investigate the therapeutic effect of programmed cell death receptor 1 (PD-1) inhibitor in drug-resistant recurrent gestational trophoblastic neoplasia (GTN).Methods:Clinicopathological features, previous treatments, PD-1 inhibitor treatment and prognosis of 8 patients with drug-resistant recurrent GTN treated with PD-1 inhibitor pembrolizumab， in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from August 2018 to June 2019 were collected and retrospectively analyzed.Results:(1) Clinicopathological features: the average age of onset of 8 GTN patients was 32.9 years old (31-39 years old); pathological types: choriocarcinoma in 7 cases, epithelioid trophoblastic tumor in 1 case. International Federation of Gynecology and Obstetrics (FIGO) stages: stage Ⅲ in 5 cases, stage Ⅳ in 3 cases; FIGO score: 4 patients with 7-12 points (high-risk group) and 4 patients with ≥13 points (ultra high-risk group). All the 8 patients had lung metastasis, 2 patients with brain metastasis, 1 patient with kidney and 1 patient with intestinal metastasis. (2) Previous treatments: ① Chemotherapy: 8 patients with GTN received an average of 21.1 courses (5-30 courses) of chemotherapy; the main route was systemic intravenous chemotherapy. One patient received intrathecal methotrexate chemotherapy due to brain metastasis. ② Surgery: 7 of 8 patients with GTN received surgical treatment, including 5 cases of pelvic surgury, 6 cases of pulmonary lobectomy and 1 case of right hemicolectomy. ③ Radiotherapy: 2 of 8 patients with GTN received radiotherapy, among which 1 patient received radiotherapy for lung for 8 times due to lung metastasis, and the other one received radiotherapy for lung, right sacroiliac joint and skull for a total of 22 times. (3) PD-1 inhibitor treatment: 8 patients with GTN received PD-1 inhibitor treatment with a mean course of 9 (2-12 courses). Six patients appeared Ⅰ-Ⅱ grade of immune related adverse events (AE), and no severe AE occurred. (4) Prognosis: after 2-3 courses of PD-1 inhibitor treatment, serum β-hCG level came to normalization in 4 patients. They were followed up for 2-7 months without any recurrence after 0-9 courses of consolidation treatment. One patient received 12 courses of PD-1 inhibitor treatment. The serum β-hCG level normalized after the 6th courses but increased 1 months later, and then received bevacizumab treatment due to the progression of the disease. The remaining 3 patients received other chemotherapy regiments due to disease progression during PD-1 inhibitor treatment.Conclusions:PD-1 could be used as a remedial treatment for drug-resistant recurrent GTN, with a high effective rate and relatively mild AE. However, more cases need to be accumulated clinically and efficacy should be comprehensively evaluated in combination with pathology and immunohistochemical examination.

Histone lysine specific demethylase 1 (LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound (IC = 3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound (IC = 49 nmol/L, and = 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3K4me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency of compound . Compound also showed strong antiproliferative activity against four leukemia cell lines (OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, significantly inhibited colony formation and caused remarkable morphological changes. Compound induced expression of CD86 and CD11b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation. The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazole-fused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1A inhibitors.

Objective: To understand the factors affecting the compliance of blood glucose monitoring in patients with type 2 diabetes in rural areas, and to provide evidence for improving the compliance of patients with blood glucose monitoring. Methods: A method of phenomenological study in qualitative research was conducted to conduct deep semi-structured interviews on 43 patients with poor blood glucose compliance in type 2 diabetes in rural areas, and to analyze the collected data. Results: Extracted five themes: bad experience affected compliance; lack of knowledge about blood glucose monitoring; economic and time was not sufficient; "long-term illness into a good doctor" overconfidence; social support uncertainty. Conclusions The status of blood glucose monitoring in rural type 2 diabetes patients is not optimistic. In order to improve the compliance of patients with blood glucose monitoring, nursing workers should pay attention to the mastery of blood glucose monitoring knowledge in rural type 2 diabetes patients, improve blood glucose monitoring methods and techniques, and give full play to the role of family doctors. Efforts to improve patient blood glucose monitoring compliance.

Objective To summarize and analyze the clinical outcomes of gestational trophoblastic neoplasia (GTN) patients receiving primary treatment at Peking Union Medical College Hospital from 1985 to 2015,and investigate the changes in treatment efficacy between the first and the second 15 years.Methods Clinical data of GTN patient receiving primary chemotherapy at Peking Union Medical College Hospital from January 1985 to December 2015 were retrospectively analyzed.It further compared the therapeutic results and chemotherapy cycles given to GTN patients,according to International Federation of Gynecology and Obstetrics (FIGO,2000) prognostic score system,who were classified to different stages and low-or high-risk groups.Results In total,1 711 GTN patients were included in this study.Comparing the 1985-2000 group and the 2001-2015 group,the results showed that:(1) while the overall complete remission (CR) rate was 93.7％ (1 603/1 711),the CR rate of 2001-2015 group was significantly higher than that of 1985-2000 group [98.4％ (1 155/1 174) vs 83.4％ (448/537),x2=139.353,P＜0.01].This difference was significant between stage Ⅲ and Ⅳ patients,but nonexistent between stage Ⅰ and Ⅱ patients,including low-and high-risk groups.(2) The relapse rate of patients who had been in CR was 2.7％ (43/1 603),with no significant differences between the groups of 1985-2001 and 2001-2015 [3.6％ (16/448) vs 2.3％ (27/1 155),x2=6.867,P=0.142].(3) The overall mortality rate was 2.6％ (44/1 711),which significantly decreased in 2001-2015 group compared to 1985-2000 group [1.6％ (19/1 174) vs 4.7％ (25/537),x2=13.830,P＜0.01].This difference appeared only in high-risk patients with stage Ⅲ disease (x2=9.505,P＜0.01).(4) Fluorouracil was gradually replaced by floxridine in chemotherapy regimens.The total cycles of chemotherapy regimens given to low-risk patients with stage Ⅲ disease significantly decreased in 2001-2015 group,but no statistical difference was shown with patients at other stages.Moreover,the cycles of consolidation treatment were significantly reduced in patients with stage Ⅲ patients.Conclusions GTN patients could obtain satisfactory curative results after appropriate and standard treatment.Peking Union Medical College Hospital has achieved better curative effect in the latest 15 years than before.

Objective Using a questionnaire to evaluate different regimens of chemotherapy on ovarian function and quality of life of patients with gestational trophoblastic neoplasia (GTN).Methods At least 6 months after completion of chemotherapy,200 patients with GTN treated in Peking Union Medical College Hospital from January 2010 to June 2017 were randomly selected to fill up the questionnaire.The questionnaire items were included the patient's menstrual cycles,sexual life,gestational issues and common health.The patients were divided into 3 groups by chemotherapy regimens:actinomycin D (Act-D) group,floxuridine + Act-D + vincristine (FAV) or floxuridine + Act-D + etoposide + vincristine (FAEV) group (FAV-FAEV group),and etoposide + methotrexate + Act-D (EMA)/vincristine + cyclophosphamide (CO) or EMA/ etoposide + cisplatin (EP) group (EMA/CO-EMA/EP group).Chi-square test was used with a significance level of P-value less than 0.05.Results One hundred and seventy-three (86.5％,173/200) of the patients completed the questionnaire.Forty three point two percent (43.2％,19/44) in the EMA/CO-EMA/EP group had a normal menstrual cycle,which were significantly lower than those of Act-D group (84.6％,22/26) and FAV-FAEV group (71.2％,37/52;all P＜O.05).Amenorrhea rate was also significantly higher in EMA/CO-EMA/EP group (25.0％,11/44) than in Act-D group(0) and FAV-FAEV group (17.3％,9/52;all P＜0.05).The sexual life parameters were comparable among 3 groups.Ten out of thirty-two patients conceived after chemotherapy,2 had miscarriages and 8 had full-term delivery of healthy babies.The common health and labor capacity were significantly decreased after chemotherapy (all P＜0.05).Conclusions EMA/CO or EMA/EP regimen have a worse impact on ovarian function than Act-D and FAV or FAEV regimen.Gynecologic oncologist should be concerned about the ovarian function and quality of life of GTN patients.

Objective To discuss the effects of prophylactic chemotherapy on the outcomes and prognosis of invasive mole patients.Methods One hundred and fifteen invasive mole (IM) patients older than 40 years were registered in Peking Union Medical Collage Hospital.Eleven of them were treated with prophylactic chemotherapy before diagnosed as IM prophylactic chemotherapy group,while the other 104 cases received therapeutic chemotherapy after diagnosed as IM (non-prophylactic chemotherapy group).The general clinical data (including age,clinical stage,risk factor score),treatment,outcomes and relapse of patients were retrospectively compared between two groups.Results (1) The age of prophylactic chemotherapy group and non-prophylactic chemotherapy group were (47±5) versus (46±4) years old.Ratio of clinical stage Ⅰ-Ⅱ were 3/11 versus 29.8％ (31/104),clinical stage Ⅲ-Ⅳ were 8/11 versus 70.2％ (73/104).Ratio of risk factor score 0-6 were 11/11 versus 84.6％ (88/104),risk factor score ＞6 were 0 versus 15.4％(16/104).There were no significant statistical differences between two groups in age,clinical stage or risk factor score (all P＞0.05).(2) Treatment:the total chemotherapy courses between prophylactic chemotherapy group and non-prophylactic chemotherapy group (median 7 versus 5) were significantly different (Z=3.071,P=0.002).There were no significant statistical differences between two groups in the chemotherapy courses until negative conversion of β-hCG,consolidation chemotherapy courses,total therapeutic chemotherapy courses or ratio of hysterectomy (all P＞0.05).(3) Outcomes and relapse:between the prophylactic chemotherapy group and the non-prophylactic chemotherapy group,the complete remission rate were 11/11 versus 98.1％(102/104),the relapse rate were 0 versus 1.0％(1/102).There were no significant difference between the two groups in outcomes or relapse rate (P＞0.05).Conclusions Prophylactic chemotherapy does not substantially benefit the IM patients older than 40 years.Prophylactic chemotherapy may not significantly improve patients' prognosis,in which increased sample size is required in further study.

AIM:To detect the expression of basic fibroblast growth factor (bFGF) and matrix metalloprotei-nase 9 (MMP9) in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathological features and prognosis of the patients.METHODS:The expression of bFGF and MMP9 was detected by the method of SP immunohistochemical staining in biopsy tissues of NPC patients.The relationship between the expression and the clinical significance was analyzed as well.RESULTS:In 289 cases of NPC patients, the positive rates of bFGF and MMP9 were 71.3% and 61.6%, respectively.Correlation analysis demonstrated that the expression rates of bFGF and MMP9 were both positively associated with N stage and clinical stage in NPC patients.The high expression rates of both bFGF and MMP9 were associated with poor overall survival and progression-free survival of NPC patients.Furthermore, the positive rate of bFGF was positively correlated with that of MMP9, and over-expression of both bFGF and MMP9 was correlated with the poorest survival outcomes in NPC patients.CONCLUSION:bFGF and MMP9 are over-expressed in NPC tissues and significantly associated with NPC recurrence and poor outcome.The combined interpretation of bFGF and MMP9 expression levels leads to refinement of the risks for the NPC patients and could be chosen as the prognostic biomarkers.

Objective:To investigate the clinical curative effect of vitreous cavity injection combined with transconjunctival sutureless vitrectomy on the patients with poliferative diabetic retinopathy.Methods:80 patients with diabetic retinopathy were enrolled in our hospital from January 2014 to January 2016,in which contained 83 sicked eyes,and randomly divided into two groups.Group A (n=40,42 sicked eyes) accepted 25G transconjunctival sutureless vitrectomy,and Group B (n=40,41 sicked eyes) adopted intravitreal injection of conbercept based on patients in Group A.The operative conditions,best-corrected visual acuity (BCV) and retinal thickness were compared between two groups,and the incidence of adverse reactions within postoperative 1 month were recorded and analyzed.Results:The operation time of group B was significantly shorter than that of group A (P＜0.05).The percentage of using electric coagulation,operative bleeding and iatrogenic fracture space in group B were significantly lower than of those group A (P＜0.05).The percentage of neovascularization vanish in group B was significantly higher than that of group A (P＜0.05).The BVCA of patients in group B in postoperative 1 month and 3 month were higher than those of group A (P＜0.05).And the thickness of retinal in group B were significantly thinner than those of Group A (P＜0.05).The incidence of vitreous hemorrhage and hyphema in group B were significantly lower than those of Group A (P＜0.05).Conclusions:Vitreous cavity injection combined with transconjunctival sutureless vitrectomy improved the operative conditions and contributed to the recovery of postoperative visual acuity and retinal in the treatment of patients with poliferative diabetic retinopathy.

Objective:To investigate the effects of xuesaitong on the retinal microcirculation of patients with diabetic mtinopathy (DR).Methods:Ninety-five patients with DR admitted in our hospital were randomly divided into the control group and the observation group.Forty-eight patients in the control group were treated with conventional hypoglycemic agent,and those in the observation group were treated with xuesaitong.The retinal microcirculation indexes including EDV,PSV,RI,Vmax,Vmin,MV,hemorheology indexes including NBL,NBH,DE,Hct,AE,ESR,and clinical efficacy in both groups were observed and compared.Results:After treatment,the clinical efficacy of observation group was 87.8％,which was much higher than that of the control group (61.4％,P＜0.05).The EDV,Vmax,and Vmin of control group were significantly improved than those before treatment (P＜0.05),and EDV and PSV were much higher than those of control group,the RI,Vmax,Vmin,and MV were much lower (P＜0.05).Additionally,the NBL and NBH in control group were much lower compared with those before treatment,while NBL,NBH,DE,Hct,AE,and ESR in control group were improved than those in control group,which were much improved that those of control group (P＜0.05).Conclusion:Xuesaitong combined with conventional hypoglycemic therapy was effective in treating patients with diabetic retinopathy,which could significantly improved the retinal microcirculation and hemorheology.

Objective To investigate which methods can promote the serum microRNA extract production.Methods The sera of healthy persons were treated with 10％ SDS (sodium dodecyl sulfate) and/or sonication at first,then extracted miRNA by routine Trizol method,or the serum miRNA was just extracted by routine Trizol method.The contents of serum miRNA-218 and miRNA-346 were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) technique,and qRT-PCR relative quantities among different groups were compared to evaluate influence of different methods on microRNA extract efficacy.Results Compared to routine Trizol extraction method,the qRT-PCR relative quantities of miRNA-218 and miRNA-346 were improved when serum was treated with 10％ SDS and/or sonication at first (P ＜0.05),which was most obviously improved when treated with 10％ SDS combined with sonieation.Conclusions The method that serum was treated with SDS incubation and sonication at first can promote sensitivity of serum microRNA detection.