A young female patient with acne and elevated testosterone level underwent plasma steroid hormones testing and found a significant increase in aldosterone. We excluded testing interference and verified the absence of hypertension, hypokalemia, and adrenal occupancy, as well as primary and secondary hyperaldosteronism. During follow-up, a temporal correlation was found between aldosterone levels and the use of drospirenone and ethinylestradiol tablets. It was observed that the combination of drospirenone and ethinylestradiol could lead to the increase of aldosterone level and the concentration ratio of aldosterone to direct renin through different mechanisms. Drospirenone exerts an antagonistic effect on mineralocorticoid receptor to prevent the development of hypertension or hypokalemia. In clinical practice, it is necessary to pay attention to the effect of this drug on screening markers for primary aldosteronism. In the laboratory examination, when female patients with no symptoms of hypertension and hypokalemia but with elevated aldosterone levels are encountered, it can be verified whether they have a history of use of compound estrogen-progestin such as drospirenone and ethinylestradiol tablets, and appropriate tips are provided in the report.

Objective To investigate the effect of verbascoside(VB)on endothelial dysfunction in atherosclerotic(AS)rats by regulating high-mobility group protein B1(HMGB1)/receptor for advanced glycation endproducts(RAGE)/nuclear factor κB(NF-κB)signal pathway.Methods The rat model of AS was established by high fat feeding combined with vitamin D3 solution intraperitoneal injection.Rats were divided into the control group(n=10),the model group(n=12),the low(VB-L),medium(VB-M)and high dose(VB-H)VB groups(2,5 and 10 mg/kg,n=10),and the positive control group(simvastatin,5 mg/kg,n=10).The serum level of blood lipids was detected by automatic biochemical analyzer.Pathological changes of aorta were observed by HE staining.Serum levels of inflammatory factors and vascular endothelial cytokines were detected by enzyme-linked immunosorbent assay(ELISA).The level of oxidative stress in rats was detected by micro-method kit.The expression of HMGB1/RAGE signal pathway protein in aorta was detected by Western blot assay.Results Compared with the control group,the intima of aorta in the model group was thickened,plaque appeared in blood vessels,accompanied by lipid deposition and inflammatory cell infiltration.Serum levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),C-reactive protein(CRP),matrix metalloproteinase-9(MMP-9),endothelin-1(ET-1),visfatin,intercellular adhesion molecule-1(ICAM-1)and malondialdehyde(MDA),and HMGB1,RAGE and phosphorylation levels of NF-κB in aorta were obviously increased.Serum levels of high-density lipoprotein cholesterol(HDL-C),nitric oxide(NO),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were obviously decreased(P＜0.05).Compared with the model group,pathological changes of rats were obviously improved in the VB-L,VB-M and VB-H groups and the simvastatin group.Serum levels of TC,TG,LDL-C,TNF-α,IL-1β,CRP,MMP-9,ET-1,visfatin,ICAM-1,MDA,and HMGB1,RAGE,phosphorylation levels of NF-κB in aorta were obviously decreased,and serum levels of HDL-C,NO,SOD and GSH-Px were obviously increased(P＜0.05).Conclusion VB can down-regulate the expression of HMGB1/RAGE/NF-κB signal pathway protein,inhibit inflammation and oxidative stress in AS rats,and improve lipid metabolism and vascular endothelial function.

Thimerosal has been widely used as a preservative in drug and vaccine products for decades.Due to the strong propensity to modify thiols in proteins,conformational changes could occur due to covalent bond formation between ethylmercury(a degradant of thimerosal)and thiols.Such a conformational change could lead to partial or even complete loss of desirable protein function.This study aims to investigate the effects of thimerosal on the capsid stability and antigenicity of recombinant human papillomavirus(HPV)18 virus-like particles(VLPs).Dramatic destabilization of the recombinant viral capsid upon thimerosal treatment was observed.Such a negative effect on the thermal stability of VLPs preserved with thimerosal was shown to be dependent on the thimerosal concentration.Two highly neutralizing antibodies,13H12 and 3C3,were found to be the most sensitive to thimerosal treatment.The kinetics of antigenicity loss,when monitored with 13H12 or 3C3 as probes,yielded two distinctly different sets of kinetic parameters,while the data from both monoclonal antibodies(mAbs)followed a biphasic expo-nential decay model.The potential effect of thimerosal on protein function,particularly for thiol-containing proteinaceous active components,needs to be comprehensively characterized during formulation development when a preservative is necessary.

Objective:To analyze the interim clinical efficacy of laparoscopic and open distal gastrectomy for gastric cancer in elderly patients.Methods:The prospective randomized controlled study was conducted. The clinicopathological data of 102 patients aged ≥65 years who underwent distal gastrectomy for gastric cancer in the Nanfang Hospital of Southern Medical University from September 2014 to May 2018 were collected. After excluding 6 patients, 96 patients were finally included. Based on random number table, patients were allocated into two groups. Patients undergoing laparoscopic distal gastrectomy were allocated into laparoscopic group, and patients undergoing open distal gastrectomy were allocated into open group, respectively. Obser-vation indicators: (1) grouping situations of the enrolled patients; (2) intraoperative situations; (3) postoperative situations; (4) follow-up. Follow-up using outpatient examination and telephone interview was conducted to detect complications in the postoperative 30 days up to July 2018. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M( P25, P75) or M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter Mann-Whitney U test. Results:(1) Grouping situations of the enrolled patients: a total of 96 patients were selected for eligibility. There were 66 males and 30 females, aged from 65 to 85 years, with a median age of 69 years. There were 49 of 96 patients in the laparoscopic group and 47 patients in the open group. (2) Intraoperative situations: patients in the two groups underwent distal gastrectomy successfully with D 2 lymphadenectomy, without intra-operative conversion to laparotomy. The volume of intraoperative blood loss and surgical incision length were 50 mL(50 mL,100 mL) and (7.1±1.7)cm for the laparoscopic group, respectively, versus 100 mL(100 mL,200 mL) and (19.1±1.7)cm for the open group, showing significant differences between the two groups ( Z=?3.779, t=?34.880, P<0.05) . (3) Postoperative situations: the number of lymph node dissected, time to postoperative initial out-of-bed activities, time to postoperative first flatus, time to postoperative first liquid food intake, time to postoperative first semi-liquid food intake, time to drainage tube removal, duration of postoperative hospital stay were 49(35,62), 1.9 days(1.3 days,2.9 days), 2.6 days(2.2 days,2.9 days), 3.4 days(2.7days,4.0 days), 5.9 days(4.7 days,7.7 days), 4.9 days(3.5 days,6.8 days), 7.7 days(6.7 days,8.9 days) for the laparoscopic group, respectively, versus 40(27,51), 2.5 days (1.8 days,3.3 days), 2.6 days(2.2 days,2.9 days), 3.9 days(2.9 days,5.7 days), 4.9 days(3.9 days, 5.9 days), 6.3 days(4.7 days,8.9 days), 8.7 days(6.9 days,11.7 days), showing significant differences between the two groups ( Z=?2.354, ?2.210, ?2.743, ?2.474, ?2.906, ?2.503, ?2.359, P<0.05). (4) Follow-up: patients in the two groups received 30 days of follow-up. During the follow-up, 8 patients in the laparoscopic group had postoperative complications, including 1 case with Clavien-Dindo grade Ⅰ complications, 7 cases with Clavien-Dindo grade Ⅱ complications, and no patient with Clavien-Dindo grade Ⅲ complications. Thirteen patients in the open group had postoperative complications, including 2 cases with Clavien-Dindo grade Ⅰ complications, 10 cases with Clavien-Dindo grade Ⅱ complications, and 1 case with Clavien-Dindo grade Ⅲ complications. There was no significant difference in the above indicators between the two groups ( χ2=1.135, 1.973, 1.054, P>0.05). The overall complication rate was 16.3%(8/49) and 27.7%(13/47) for the laparoscopic group and open group, respectively, showing no significant difference between the two groups ( χ2=1.803, 99.7% confidence interval as ?∞ to 2.4%, P>0.05). The upper limit of 99.7% confidence interval was less than non-inferiority level of 15%, interim analysis of which showed that the complication rate of the laparoscopic group was non-inferior to the open group. Conclusion:For elderly patients undergoing laparoscopic or open distal gastrectomy for gastric cancer, laparoscopic surgery does not increase intraoperative or postoperative complications, and has advantages of minimally invasiveness, fine operation, quicker recovery, and shorter hospital stay. Registry: this study was registered at clinicaltrials.gov in United States, with the registry number of NCT02246153.

Objective:This study evaluates the efficacy and safety of dasatinib combined with a multi-agent chemotherapy regimen of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients. Methods:This prospective, single-arm, and open clinical study enrolled 30 adult Ph + ALL patients who were newly diagnosed and treated from January 2016 to April 2018 in the center of this study. Standard induction chemotherapy was given for 4 weeks. However, dasatinib (100 mg/d) was continuously administered from day 8 until the end of the whole therapy in the induction therapy. Patients who are available for allogeneic or autologous stem cell transplantation (SCT) received transplantation when the disease was evaluated as complete remission. Results:All 30 patients achieved hematological complete remission (HCR) after the induction chemotherapy, and 70.0% (21/30) of them achieved the accumulated molecular complete remission (MCR) . The patients were followed up with a median follow-up time of 37.8 months (32.0-46.6) . The 3 year overall survival (OS) and 3 year hematological relapse-free survival (HRFS) were 68.1% and 61.6%, respectively. Moreover, 63.3% and 43.3% of the patients achieved molecular major remission and MCR, respectively. Consequently, 60.0% of the patients achieved MCR until 6 months. The patients who achieved MCR within 6 months had superior OS ( P=0.004) , HRFS ( P=0.049) , and event-free survival (EFS; P=0.001) . Fifteen patients (50.0%) received SCT at the first HCR. However, HRFS ( P=0.030) and EFS ( P=0.010) in the SCT group were better than those in the chemotherapy group. Conclusions:The regimen of dasatinib combined with a multi-agent chemotherapy was proven safe and effective in the treatment of newly diagnosed adult Ph + ALL patients. Clinical trial registration:ClinicalTrials.gov, NCT02523976.

OBJECTIVE： To screen the best proportion of Astragalus membranaceus injection combined with Erigeron breviscapus injection against cerebral ischemia-reperfusion injury in rats. METHODS： Male SD rats were randomly divided into sham operation group， model group and administration group [different A. membranaceus injection-E. breviscapus injection proportion groups， being A（0 ∶ 10）， B（2 ∶ 8）， C（4 ∶ 6）， D（6 ∶ 4）， E（8 ∶ 2）， F（10 ∶ 0）groups， set by baseline geometric proportion increasing and decreasing design]， with 8 rats in each group. Except for sham operation group， reperfusion injury model of middle cerebral artery occlusion were induced by modified suture method in rats. The each administration group was given relevant medicine intraperitoneally once immediately after inducing model， and then given again after 24 hours （medication interval between the two injections of 30 min）. Constant volume of normal saline was given to rats in sham operation group and model group. Forty-eight hours after reperfusion， Longa scoring method was used to evaluate neurological impairment of rats， and neurological impairment score was recorded. Serum content of MDA and activity of SOD were measured by colorimetry assay. TTC assay was used to detect cerebral infraction， and cerebral infarction rate was calculated. Kim’s formula was used to calculate the synergistic index （q） of rats in administration groups. RESULTS： Compared with sham operation group， neurological impairment score and serum content of MDA were increased significantly in model group， while activity of SOD was decreased significantly （P＜0.01）. The area of cerebral infarction increased significantly， and the rate of cerebral infarction increased significantly （P＜0.01）. Compared with model group， neurological impairment scores and serum contents of MDA were decreased significantly in group A， B， C， D and E； neurological impairment score of group C was significantly lower than those of group A and F； serum contents of MDA in group B， C， D and E were significantly lower than that of group F （P＜0.05 or P＜0.01）. Activities of SOD in group A， B， C， D and E were increased significantly， and group C was significantly higher than group F （P＜0.05 or P＜0.01）. The cerebral infarction area of rats in each administration group was reduced to varying degrees. The cerebral infarction rates of rats in group B， C， D and E were significantly reduced， and group C and D were significantly lower than group F， while group C was significantly lower than group A （P＜0.05 or P＜0.01）. The q values of group B， C， D and E were 0.90， 1.30， 1.00， 0.70 （neurological impairment score） and 0.79， 1.27， 0.98， 0.82 （cerebral infarction rate）. CONCLUSIONS： Different ratios of A. membranaceus injection and E. breviscapus injection have certain protective effects on cerebral ischemia-reperfusion injury model rats， can relieve their neurological deficits， alleviate their oxidative stress and reduce their cerebral infarction areas. The effect of the combination of the two drugs is better than that of single use， and the optimum ratio is 4 ∶ 6.

Objective: To analyze the clinical and laboratory characteristics, and prognosis of adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. Methods: The medical records of 92 adult AML patients with MLL gene rearrangements from January 2010 to December 2016 were retrospectively analyzed. Results: 92 cases (6.5%) with MLL gene rearrangements were identified in 1 417 adult AML (Non-M₃) patients, the median age of the patients was 35.5 years (15 to 64 years old) with an equal sex ratio, the median WBC were 21.00(0.42-404.76)×10⁹/L, and 78 patients (84.8%) were acute monoblastic leukemia according to FAB classification. Eleven common partner genes were detected in 32 patients, 9 cases (28.1%) were MLL/AF9(+), 5 cases (15.6%) were MLL/AF6(+), 5 cases (15.6%) were MLL/ELL(+), 2 cases (6.3%) were MLL/AF10(+), 1 case (3.1%) was MLL/SETP6(+), and the remaining 10 patients’ partner genes weren’t identified. Of 92 patients, 83 cases with a median follow-up of 10.3 (0.3-74.0) months were included for the prognosis analysis, the complete remission (CR) rate was 85.5% (71/83), the median overall survival (OS) and relapse free survival (RFS) were 15.4 and 13.1 months, respectively. Two-year OS and RFS were 36.6% and 29.5%, respectively. Of 31 patients underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT), two-year OS and RFS for patients received and non-received allo-HSCT were 57.9% and 21.4%, 52.7% and 14.9%, respectively (P<0.001). Among patients with partner genes tested, 9 of 32 cases (28.1%) were MLL/AF9(+), the median follow-up was 6.0(4.1-20.7) months. 3 patients with MLL/AF9 underwent allo-HSCT. 23 cases (71.9%) were non- MLL/AF9(+), the median follow-up was 7.8 (0.3-26.6) months. 14 patients (60.1%) with non-MLL/AF9 underwent allo-HSCT. One-year OS for patients with MLL/AF9 and non-MLL/AF9 were 38.1% and 55.5%, respectively (P=0.688). Multivariate analysis revealed that high WBC (RR=1.825, 95% CI 1.022-3.259, P=0.042), one cycle to achieve CR (RR=0.130, 95% CI 0.063-0.267, P<0.001), post-remission treatment with allo-HSCT (RR=0.169, 95% CI 0.079-0.362, P<0.001) were independent prognostic factors affecting OS. Conclusions AML with MLL gene rearrangements was closely associated with monocytic differentiation, and MLL/AF9 was the most frequent partner gene. Conventional chemotherapy produced a high response rate, but likely to relapse, allo-HSCT may have the potential to further improve the prognosis of this group of patients.

Objectives: To investigate the influence of duration of antibiotic therapy on the prognosis of patients with AML who had Gram-negative bloodstream infection during consolidation chemotherapy. Methods: Data were collected retrospectively from 591 patients enrolled from the registered "A Phase III study on optimizing treatment based on risk stratification for acute myeloid leukemia, ChiCTR-TRC-10001202" treatment protocol between September 2010 and January 2016 in different treatment cycles. Results: A total of 119 episodes of Gram-negative bloodstream infection occurred during consolidation chemotherapy. Excluding the 5 episodes in which fever lasted longer than 7 days, 114 episodes of infection were analyzed. The median neutrophil count was 0 (0-5.62)×10⁹/L, median neutropenia duration was 9 (3-26) days, median interval of antibiotics administration was 7 (4-14) days. Logistic regression analysis showed that there is no significant difference on 3-day recurrent fever rate and reinfection by the same type bacteria between antibiotics administration ≤7 days or >7 days (1.2% vs 3.0%, P=0.522, OR=0.400, 95% CI 0.024-6.591; 18.5% vs 21.2%, P=0.741, OR=0.844, 95% CI 0.309-2.307). Propensity score analysis confirmed there was no significant difference on same pathogen infection rate between antibiotics application time ≤ 7 days or >7 days (P=0.525, OR=0.663, 95% CI 0.187-2.352). No infection associated death occurred within 7 or 30 days in both groups. Conclusion Discontinuation of therapy until sensitive antibiotics treated for 7 days does not increase the recurrent fever rate and the infection associated death rate. Indicating that, for AML who had Gram-negative bloodstream infection during consolidation chemotherapy, short courses of antibiotic therapy is a reasonable treatment option when the infection is controlled.

Objective: To analyze the clinical, laboratory characteristics and prognosis of adult early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Methods: The clinical data of 13 adult ETP-ALL patients from January 2009 to March 2017 were retrospectively analyzed and compared with non-ETP ALL patients. Results: 13 ETP-ALL patients (17.3%) were identified in 75 adult T-ALL patients, the median age of the patients was 35 years old (15 to 49 years) and 10 patients were male (76.9%). ETP-ALL patients had lower WBC count, LDH level, blasts in peripheral blood, lower incidence of thymic mass and higher PLT count compared to non-ETP ALL patients. The CR rate after one course induction chemotherapy for ETP-ALL and non-ETP ALL patients was 33.3% and 90.1%, respectively (χ²=26.521, P<0.001). The median overall survival(OS) was 11.33 (95%CI 0-28.46) and 25.69 (95%CI 11.98-39.41) months, respectively. The 3-year OS was 41.7% and 40.7%, respectively (P=0.699). The median event free survival (EFS) was 1.51 (95%CI 1.23-1.79) and 21.36 (95%CI 4.67-38.04) months, respectively. The 3-year EFS was 16.7% and 39.5%, respectively (P=0.002). The 3-year relapse free survival (RFS) was 53.0% and 52.0%, respectively (P=0.797). Multivariate analysis revealed that CNSL and allo-HSCT were independent risk factors affecting OS of T-ALL and ETP-ALL didn’t affect the prognosis of T-ALL. Conclusion To our knowledge, this study is the first report on characteristics and prognosis of adult ETP-ALL patients in China. At total of 13 T-ALL patients (17.3%) were classified as having ETP-ALL. These patients had a lower leukemia burden and lower CR rate after one course induction compared to non-ETP ALL patients. Allo-HSCT can improve the prognosis of ETP-ALL.

Objective To investigate the characteristics of NPM-MLF1 fusion gene in acute myeloid leukemia (AML). Methods The data of one AML patient with NPM-MLF1 fusion gene was analyzed,and literatures were reviewed. Results A female patient was diagnosed as AML M6. In the course of the disease, 2 hematologic relapsed, and 2 recurrences were associated with NPM-MLF1 fusion gene positive. After inductive treatment, hematologic complete remission was achieved, and NPM-MLF1 fusion genes were all negative. Survival time surpassed 6 years when the chemotherapy was performed alone. Conclusion The incidence of NPM-MLF1 fusion gene in AML is low. It is necessary to collect more clinical data to judge whether an independent disease type or not.