Objective To determine the ultrastructural localization of MDR1 and GFAP in the surgically resected brain tissues from intractable epilepsy patients. Methods Expression of MDR1 and GFAP in brain tissues was examined by using PAG immunolabeling technique for electron microscopy. Results The MDR1 and GFAP labeled by gold particles were only detected at some reactive astrocytes. The positive gold particles were mainly located in the astrocytic cytoplasm and their membrane, but not in the nucleus.Conclusion The expression of MDR1 and GFAP in the brain of patients with clinically intractable epilepsy were mainly located at the cytoplasm and membrane of certain reactive astrocytics.;

Tetramethylpyrazine (TMP) is a herb used widely in Traditional Chinese Medicine (TCM) as an antianginal drug. The exact mechanism whereby TMP treat ischemic heart disease is still not fully understood. The purpose of this study is to examine the anti-inflammatory effect of TMP in patients with acute coronary syndromes (ACS). Methods Thirty-two patients with acute myocardial infarction or unstable angina were randomly assigned to TMP group or control group. All patients received the same standard treatment. Patients in TMP group received TMP 3mg/kg every 12 hours for 5 days. Plasma concentrations of high-sensitivity Creactive protein (CRP), serum amyloid A (SAA) and plasminogen activator inhibitor-1 (PAI-1) were measured at baseline and after 5 days of therapy. Results Both CRP and SAA concentrations increased significantly in control group (P＜0.05) whilst in TMP group, only SAA had a significant increase (P＜0.05); the absolute increase of CRP, SAA, and PAI-1 were significantly less in TMP group than in control group (P＜0.05). Conclusion TMP has an anti-inflammatory and profibrinolytic effect in patients with ACS. These effects may contribute to the clinical benefits of TMP in ischemic heart disease.

Objective To retrospectively analyze the relationship between benign prostatic hyperplasia (BPH) and metabolic syndrome (MS) in senior patients. Methods The 859 male senior patients including 619 cases with BPH and 8 cases with MS were enrolled in this study, and there were 192 cases with both diseases and 40 controls. The levels of fasting blood glucose (FBG), total cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured. The body mass index (BMI), prostate volume and annual prostate growth rate were determined or calculated. The correlations of BPH with other metabolic risk factors were analyzed. Results The levels of systolic blood pressure (SBP), diastolic blood pressure (DBP), body weight, BMI, TG and FPG were higher (t=6.15, 5.99, 13.12, 15.56, 10.63 and 9.94, all P＜0.01), while serum HDL-C level was lower (t=-7.57,P＜0.01) in BPH patients with MS than without MS. As the number of components of MS was increased, the prostate volume was increased (F=2.98, P=0.031). As the age, body weight, BMI, SBP and PG were increased, the prostate volume was increased (t=-6.39,-2.39,-2.36,-2.13,-25.85,all P＜0.05). Spearman analysis showed that prostate volume was positively correlated with age, SBP, body weight, BMI and hypertension (r=0.229, 0.079, 0.090, 0.089 and 0.088, all P＜0.05). And age, body weight and SBP were the independent risk factors for BPH (OR=1.07, 1.03 and 1.34, all P＜0.05). Conclusions The present study demonstrates a relationship between BPH and MS in senior patients. Future studies are needed to confirm our results and to explain underlying mechanisms.

Objective:To investigate the progression pattern of acquired resistance to osimertinib and the treatment method as well as the therapeutic effect of salvage therapy in advanced lung cancer patients with epidermal growth factor receptor (EGFR) sensitive mutation or T790M mutation after the treatment of tyrosine-kinase inhibitor (TKI).Methods:The data of 145 patients with advanced lung cancer treated with osimertinib in Jiangsu Cancer Hospital between April 2017 (the approval time of osimertinib in China) and May 2019 were collected. At the last follow-up (December 2019), a total of 87 (60.0%) patients had acquired resistance to osimertinib, 61 (70.1%) of whom received salvage treatment; for patients with dramatic progression after resistance, chemotherapy was mainly given in the salvage therapy; for patients with gradual or local progression after resistance, the continuing targeted drug therapy and the local therapy were given. Imaging evaluation and Kaplan-Meier method were used to analyze the progression pattern of acquired resistance to osimertinib and the survival status, and to compare the salvage treatment results among subgroups.Results:The median follow-up time of 61 patients receiving salvage therapy was 11 months (4-32 months), among which 58 (95.1%) patients again had resistance to osimertinib, and 24 (39.3%) patients died of lung cancer. The median progression-free survival (PFS) time and overall survival (OS) time for the whole cohort was 2.5 months (95% CI 2.1-3.0 months) and 19.0 months (95% CI 13.7-26.3 months), respectively. The 1-year and 2-year OS rate was 72.1% and 41.7%, respectively. Among 61 patients receiving salvage therapy, 8 (13.1%) , 30 (49.2%) and 23 (37.7%) cases had dramatic progression, gradual progression and local progression, respectively; when given timely and proper salvage treatment, there were no statistically differences in PFS and OS of the patients in the above three subgroups (all P>0.05). There were no statistically differences in PFS and OS between patients receiving local therapy (24 cases) and patients not receiving local therapy (37 cases) after the progression occurred (all P>0.05). Among 58 patients with resistance to osimertinib again after the salvage therapy, 6 patients with gradual or local progression had more than 6-mouth PFS after the salvage therapy. Conclusions:Dramatic, gradual and local progression are the main patterns in patients with acquired resistance to osimertinib. The therapeutic efficacy of salvage therapy still shows some disappointing results.

Objective To study the subacute inhalation toxicity of Ivermectin TC, and obtain its non-observed adverse effect level(NOAEL).Methods It was performed on the doses of Ivermectin TC 190, 380, 750 mg/m3, the solvent control group (0.03%Tween-80 solution) , the control group and additional group ( there were 6 female and 6 male Sprague-Dawley rats for each group) .The animals inhaled with nose-only exposure for 4 weeks (4 h/d, 5 d/week) .The additional group should be observed another 14 days after exposing.At the end of experiment, the rats were killed, the routine and biochemical detection, the body weight and organ to body weight ratios were all measured.Results In the high exposure group, clinical signs of rats included hair fluffy, dull, salivation, tremors were recorded at the exposure period;in female rats, feed efficiency was decreased, ALT and liver to body weight ratio were increased; in male rats, BUN and ALT were increased, CHOL and body weight for the 4th week were decreased.Histopathological examinations revealed that swelling in the liver cell was seen in some female rats at high exposure group.Conclusion The results suggested that the NOAEL of Ivermectin TC in SD rats was 380 mg/m3(4 h/d for 28 days).

Objective: To investigate the effects of cigarette smoking in different manners on acute lung injury in rats .Methods: The commercially available cigarettes with tar of 1,5, 11 mg were smoked in Canada depth smoking ( health canada method , HCM) manner , and those with tar of 11 mg were also smoked in international standard ( ISO) smoking manner .Rats were fixed and exposed to mainstream in a manner of nose-mouth exposure .After 28 days, the bronchoalveolar lavage fluids from left lung were collected for counting and classification of inflammatory cells and determination of pro -inflammatory cytokines IL-1βand TNF-α.The right lungs were subjected to histological examination and determination of myeloperoxidase ( MPO ) and superoxide dismutase (SOD) activities and glutathione , reactive oxygen species (ROS) and malondialdehyde (MDA) levels.Results:In both HCM and ISO manners , the degree of lung injury was closely related to the tar content of cigarettes , and significant decrease in the body weight of rats was observed after smoking for one week .In a HCM manner , smoking with cigarette of 11 mg tar resulted in robust infiltration of macrophages , lymphocytes and neutrophils into lungs , significant increase in IL-1βand TNF-αlevels and MPO activities , and significant decrease in GSH levels and SOD activities and increase in ROS and MDA levels ( all P <0.05 ) .Smoking with cigarette of 5 mg tar led to moderate increase in IL-1βand TNF-αlevels, and MPO activities (all P<0.05), and moderate decrease in GSH levels and SOD activities and increase of ROS and MDA levels ( all P<0.05).However, smoking with cigarette of 1 mg tar affected neither inflammatory cell infiltration nor IL-1βand TNF-αlevels.Conclusion: Cigarette smoking in nose-mouth exposure manner can induce acute lung injury in rats; and the degree of lung injury is closely related to the content of tar and other hazards in cigarettes .

Objective: To analyze the association of cytogenetic abnormalities with the prognosis of chronic myeloid leukemia (CML) patients in tyrosine kinase inhibitors (TKI) era. Methods: Karyotype analysis of chromosome G-banding was carried out in 387 newly diagnosed CML patients by short-term culture of bone marrow cells. The correlation of cytogenetic abnormalities and CML progression was explored in combination with ABL tyrosine point mutations. Result: Of 387 patients with positive BCR-ABL fusion gene assayed by fluorescence in situ hybridization (FISH) technique, 94.1% (364/387) patients were Ph positive and 5.9% (23/387) Ph negative; 320 patients (87.9%) had a translocation t (9;22) (q34;q11) and 5 (1.4%) a variant translocation t (v;22) . Additional cytogenetic aberrations (ACA) at diagnosis were found in 10.7% (39/387) Ph⁺ patients, major route ACA in 22 (56.4%) cases and minor route ACA in 15 (38.5%) cases and 2 patients (5.1%) lacked the Y chromosome (−Y) ; 23.4% (71/303) patients occurred ACA during TKI treatment and the most frequent abnormalities were abnormal chromosome numbersd, which were likely associated with high proportion of disease progression (χ²=168.21, P<0.001) and ABL tyrosine point mutations (χ²=29.04, P<0.001) . Newly diagnosed CML-CP patients with t (9;22) (q34;q11) had a longer event-free survival (EFS) and disease-free survival (DFS) rates than that of patients with ACA (P=0.037; P=0.003) , while the overall survival (OS) had no significant differences (P=0.209) . As for CML-CP patients that occurred ACA during TKI therapy would have a marked low OS, EFS and DFS (all P<0.001) compared with no ACA occurred patients. Survival of advanced patients that occurred ACA were dramatically reduced. Conclusion ACA often emerged during the disease progress in CML patients, regular and timely detection of chromosomes karyotype and ABL tyrosine point mutations during TKI treatment was important for therapeutic evaluation, progress and prognosis of CML.

Objective: To investigate the clinical implications of p16 gene deletion in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) . Methods: Retrospective analysis of clinical, immunophenotypic, cytogenetics, molecular characteristics and prognosis of 80 newly diagnosed Ph⁺ ALL patients with p16 deletion. Results: Of 80 adult Ph⁺ ALL, the prevalence of p16 gene deletion was 31.3%. p16 gene deletion carriers frequently accompanied with high WBC counts (WBC≥30×10⁹/L) and CD20 expression. The incidence of complex chromosome abnormality in p16 gene deletion group was higher than that in non-deletion group, with alternations in chromosome 7, 8, 19 and der (22) more frequently observed. There was no difference occurred between patients with or without p16 gene deletion in complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs) . However, after three cycles of chemotherapy, the MMR and CMR rate in the p16 gene deletion group was lower than patients with wild-type p16 gene (P=0.034, P=0.036) . The p16 gene deletion patients showed no significant differences in MMR, CMR and relapse rate between Imatinib or Dasatinib plus chemotherapy (P>0.05) . Deletion of p16 gene was significantly associated with poor outcomes including worse overall survival (OS) (37.1% vs 54.1%, P=0.037) , lower disease free-survival (DFS) (12.4% vs 45.9%, P=0.026) , and increased cumulative incidence of relapse (P=0.033) . Among the 25 patients with p16 deletion, 14 underwent allo-HSCT and the median survival was 21 months, better than that of patients received chemotherapy alone (12 months) (P=0.030) . Conclusion This study indicated that deletion of p16 was associated with poor prognosis in adult Ph⁺ ALL, and the utility of second-generation TKI (Dasatinib) does not necessarily have an edge on efficacy over Imatinib, but allo-HSCT has the potential of elongating life expectancy. It is an important significance to define the status of p16 in Ph⁺ ALL for predicting prognosis and guiding therapy decision-making.

Objective: To analyze the current status of work-related musculoskeletal disorders (WMSDs), work fatigue and musculoskeletal pain in Chinese occupational population, and to study the relationship between work fatigue and musculoskeletal pain and WMSDs. Methods: A total of 66 961 employees from 323 enterprises in 15 key industries in China were selected as the study subjects using stratified cluster sampling method. The incidence of WMSDs in the past year was investigated using the Chinese version of the Musculoskeletal Disorders Questionnaire, and the work fatigue and musculoskeletal pain were investigated using Borg 6-20 Rating of Perceived Exertion Scale and visual analogue scale. The data were standardized using the age composition data of 18 to 60 years from the seventh national population census. Results: The standardized annual incidence of WMSDs was higher in the front-line workers than that in the administrative and other supportive staff (38.82% vs 36.30%). The detection rates of work fatigue and musculoskeletal pain in the study subjects were 44.54% and 63.08%, respectively. The result of S-curve fitting showed that the risk of WMSDs increased with the level of work fatigue (P<0.01). Among the front-line workers, the average of monthly fatigue frequency in the neck, shoulder, lower back, upper back, wrist/hand, foot and ankle, knee, leg, and elbow were higher in the group with WMSDs compared to those without WMSDs (all P<0.01). The pain degree of musculoskeletal pain was higher in all nine sites in the fatigued group than in the no-fatigue group (all P<0.01). The standardized detection rate of musculoskeletal pain was higher in the fatigued group than in the non-fatigued group (80.38% vs 25.71%). The work fatigue was moderate and positively correlated with musculoskeletal pain in all seven sites except the lower back and elbow, with Kendall Tau-b correlation coefficients ranging from 0.423 to 0.546 (all P<0.01). Conclusion: There is a good correlation between work fatigue and local musculoskeletal pain, work fatigue and WMSDs in Chinese occupational population. Implementing ergonomic interventions to control the development of work fatigue can be an effective measure for preventing WMSDs.

Objective To investigate the association between single nucleotide polymorphisms(SNPs)of YTHDF1 rs6011668,HNRNPA2B1 rs2070601 and rs76558212 with the risk of gastric cancer.Methods A total of 457 cases with gastric cancer and 525 healthy controls were collected.The candidate SNPs were genotyped using Hi-SNP genotyping methods by multiplex rounds of PCR and high-throughput sequencing;the association between the three SNPs with the risk of gastric cancer was analyzed by test and Logistic regression.Multifactorial logistic regression and Risk Score(RS)model was used to analyze the influence of environmental and genetic factors on the risk of gastric cancer.Results YTHDF1rs6011668 TT genotype carriers had 3.075 times higher risk of gastric cancer than CC genotype carriers(95%CI:1.128～8.382,P = 0.028),and 2.961 times higher risk than CC/TC genotypes carriers(95%CI:1.091～8.033,P = 0.033).Subgroups-analysis revealed that TT genotype mainly increased the risk of gastric cancer in non-tea drinkers,pickled food eaters and fried food eaters(P<0.05).In addition,TT genotype carriers had the increased risk of gastric cancer infiltration,lymph node metastasis,distal metastasis and intermediate to advanced stages(P<0.05).The RS of the case and control groups were calculated by combining environmental and genetic factors.The higher the RS score,the higher the risk of gastric cancer was found in the RS quartile groups.Compared with the RS