Objective:To investigate the safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia.Methods:Data of acute ischemic stroke patients with baseline National Institutes of Health Stroke Scale(NIHSS)score≤3 and a platelet count<100×109/L were obtained from a multicenter register.Those who required anticoagulation or had other contraindications to antiplatelet therapy were excluded.Short-term safety outcomes were in-hospital bleeding events,while the long-term safety outcome was a 1-year all-cause death.The short-term neurological outcomes were evaluated by modified Rankin scale(mRS)score at discharge.Results:A total of 1868 non-cardioembolic mild stroke patients with thrombocytopenia were enrolled.Multivariate regression analyses showed that mono-antiplatelet therapy significantly increased the proportion of mRS score of 0-1 at discharge(OR=1.657,95%CI:1.253-2.192,P<0.01)and did not increase the risk of intracranial hemorrhage(OR=2.359,95%CI:0.301-18.503,P>0.05),compared with those without antiplatelet therapy.However,dual-antiplatelet therapy did not bring more neurological benefits(OR=0.923,95%CI:0.690-1.234,P>0.05),but increased the risk of gastrointestinal bleeding(OR= 2.837,95%CI:1.311-6.136,P<0.01)compared with those with mono-antiplatelet therapy.For patients with platelet counts≤75×109/L and>90×109/L,antiplatelet therapy significantly improved neurological functional outcomes(both P<0.05).For those with platelet counts(>75-90)×109/L,antiplatelet therapy resulted in a significant improvement of 1-year survival(P<0.05).For patients even with concurrent coagulation abnormalities,mono-antiplatelet therapy did not increase the risk of various types of bleeding(all P>0.05)but improved neurological functional outcomes(all P<0.01).There was no significant difference in the occurrence of bleeding events,1-year all-cause mortality risk,and neurological functional outcomes between aspirin and clopidogrel(all P>0.05).Conclusions:For non-cardioembolic mild stroke patients with thrombocytopenia,antiplatelet therapy remains a reasonable choice.Mono-antiplatelet therapy has the same efficiency as dual-antiplatelet therapy in neurological outcome improvement with lower risk of gastrointestinal bleeding.

Purpose: Patients with triple-negative breast cancer (TNBC) have an increased risk of distant metastasis compared to those with other subtypes. In this study, we aimed to identify the genes associated with distant metastasis in TNBC and their underlying mechanisms. Methods: We established patient-derived xenograft (PDX) models using surgically resected breast cancer tissues from 31 patients with TNBC. Among these, 15 patients subsequently developed distant metastases. Candidate metastasis-associated genes were identified using RNA sequencing. In vitro wound healing, proliferation, migration, and invasion assays and in vivo tumor xenograft and metastasis assays were performed to determine the functional importance of aldo-keto reductase family 1 member C2 (AKR1C2). Additionally, we used the METABRIC dataset to investigate the potential role of AKR1C2 in regulating TNBC subtypes and their downstream signaling activities. Results: RNA sequencing of primary and PDX tumors showed that genes involved in steroid hormone biosynthesis, including AKR1C2, were significantly upregulated in patients who subsequently developed metastasis. In vitro and in vivo assays showed that silencing of AKR1C2 resulted in reduced cell proliferation, migration, invasion, tumor growth, and incidence of lung metastasis. AKR1C2 was upregulated in the luminal androgen receptor (LAR) subtype of TNBC in the METABRIC dataset, and AKR1C2 silencing resulted in the downregulation of LAR classifier genes in TNBC cell lines. The androgen receptor (AR) gene was a downstream mediator of AKR1C2-associated phenotypes in TNBC cells. AKR1C2 expression was associated with gene expression pathways that regulate AR expression, including JAK-STAT signaling or interleukin 6 (IL-6). The levels of phospho-signal transducer and activator of transcription and IL-6, along with secreted IL-6, were significantly downregulated in AKR1C2-silenced TNBC cells. Conclusion Our data indicate that AKR1C2 is an important regulator of cancer growth and metastasis in TNBC and may be a critical determinant of LAR subtype features.

Genetic background can lead to differences in drug effects among different populations when they use the same drug. To delineate the pharmacogenomics and population genetic differences may help to clarify the role of polymorphisms of drug metabolism-related genes in drug effect heterogeneity among different populations. This article has summarized the latest progress on the polymorphisms of drug metabolism-related genes among different populations in China.
China ; Humans ; Pharmaceutical Preparations ; Pharmacogenetics ; Polymorphism, Genetic

Genetic factors play a key role in human athletic ability, and endurance quality and explosive power quality are the important components of athletic ability. In this review, we aimed to reveal the biological genetic mechanism of human athletic ability at the molecular level through summarizing the relationship between genetic variants and human athletic ability, including endurance quality related genetic markers angiotensin converting enzyme (ACE) gene, creatine kinase MM (CKMM) gene and explosive power quality related genetic markers alpha actinin 3 (ACTN3) gene, angiotensinogen (AGT) gene and interleukin6 (IL6) gene. Meanwhile, we also summarized the distribution of allele frequencies among various populations.
Actinin/genetics* ; Athletic Performance ; Gene Frequency ; Genetic Markers ; Genotype ; Humans ; Polymorphism, Genetic

Objective To evaluate the efficacy of ultrasound-guided transversus abdominal plane (TAP) and posterior rectus sheath (PRS) block for postoperative analgesia in the patients undergoing radical resection for gastric cancer.Methods One hundred twenty patients of both sexes,aged 18-64 yr,with body mass index of 19-25 kg/m2,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for elective radical resection for gastric cancer,were divided into 2 groups (n =60 each) using a random number table:control group (group C) and ultrasound-guided TAP and PRS block group (group T+R).Bilateral TAP (0.375％ ropivacaine 0.5 ml/kg was injected) and PRS block (0.375％ ropivacaine 0.3 ml/kg was injected) were performed before induction of general anesthesia in group T+R.Patient-controlled intravenous analgesia was provided to all the patients after surgery in the two groups,and the visual analog scale score at rest and during activity was maintained less than 4 within 48 h after surgery.The requirement for rescue analgesia within 48 h after surgery and occurrence of adverse reactions during the analgesia period were recorded.Results Compared with group C,the requirement for rescue analgesia within 48 h after surgery and incidence of nausea and vomiting were significantly decreased in group T+R (P＜0.05).Conclusion Ultrasound-guided TAP and PRS block provides better efficacy for postoperative analgesia with less adverse reactions in the patients undergoing radical resection for gastric cancer.

BACKGROUND:Differences exist between the action execution of the dominant hand and the nondominant hand during daily lives. With the increasing of the age, the dominant hand and the nondominant hand play an equaly important role in the action execution and implementation during daily lives. Previous studies mainly focus on the muscle strength of upper limbs. However, studies on the influence of joint dynamic characteristics and trajectory deviation on the occupational activities have been increased gradualy. The three-dimension motion capture and analysis have become the reliable and valid standard of the assessment of the upper limb movement. OBJECTIVE:By using the three-dimensional kinematic analyze method, to colect the data of the healthy elderly people using the upper limbs to drink water respectively with the cups of different weights and to investigate whether there is a difference between dominant and nondominant hands under different weight-bearing conditions based on upper limb kinematics METHODS: Sixteen right-handed elder people were chosen to be the experimental subjects. The upper limb motion of drinking water with different weight was captured by Vicon Nexus. By Data modeling and trajectory filtering with pipeline and data normalizing with the Matlab, the three-dimensional angle and peak value of the velocity of the should, elbow and wrist joint in the bilateral upper limbs were analyzed and compared when lifting the cups of 100, 200 and 500 g. RESULTS AND CONCLUSION:The most significant difference could be found in the three-dimensional movement angle of the elbow joint when holding the weights: there were significant differences in 100 g horizontal plane (X axis) and sagittal plane (Z axis), 200 g frontal plane (Y axis) and sagittal plane (Z axis), and 500 g three-dimensional plane (P < 0.05). Difference could be found in the peak value of three-dimension angular velocity in the shoulder, elbow and wrist joints: 100 g (shoulder jointPx=0.01; elbow jointPy=0.048,Pz=0.007), 200 g (elbow jointPy=0.033,Pz=0.005; wrist joint Py=0.035), 500 g (elbow jointPy=0.027,Pz=0.006) had significant differences (P < 0.05). There was no significant difference in the movement angle and angular velocity when holding different weights with the ipsilateral upper limb (P > 0.05). These results show that there is a difference in the movement angle and angular velocity between the dominant hand and the nondominant hand when drinking water. A great change of movement angle could be found in the X axis of the elbow joint in the dominant hand, and a great change of the movement angle could be found in the Z axis of the elbow joint in the nondominant hand. The angluar velocity in the Y axis has better changes than in the Z axis. The size of the weights has no effect on the movement of bilateral upper limbs.

AIK is a novel cationic peptide with potential antitumor activity. In order to construct the AIK expression vector by Gateway technology, and establish an optimal expression and purification method for recombinant AIK, a set of primers containing AttB sites were designed and used to create the AttB-TEV-FLAG-AIR fusion gene by overlapping PCR. The resulting fusion gene was cloned into the donor vector pDONR223 by attB and attP mediated recombination (BP reaction), then, transferred into the destination vector pDESTl 5 by attL and attR mediated recombination (LR reaction). All the cloning was verified by both colony PCR and DNA sequencing. The BL21 F. coli transformed by the GST-AIR expression plasmid was used to express the GST-AIK fusion protein with IPTG induction and the induction conditions were optimized. GST-AIR fusion protein was purified by glutathione magnetic beads, followed by rTEV cleavage to remove GST tag and MTS assay to test the growth inhibition activity of the recombinant AIR on human leukemia HL-60 cells. We found that a high level of soluble expression of GST-AIK protein (more than 30% out of the total bacterial proteins) was achieved upon 0.1 mmol/L ITPG induction for 4 h at 37 °C in the transformed BL21 F. coli with starting OD₆₀₀ at 1.0. Through GST affinity purification and rTEV cleavage, the purity of the resulting recombinant AIK was greater than 95%. And the MTS assays on HL-60 cells confirmed that the recombinant AIK retains an antitumor activity at a level similar to the chemically synthesized AIK. Taken together, we have established a method for expression and purification of recombinant AIK with a potent activity against tumor cells, which will be beneficial for the large-scale production and application of recombinant AIK in the future.
Antimicrobial Cationic Peptides ; biosynthesis ; Antineoplastic Agents ; metabolism ; Escherichia coli ; metabolism ; Genetic Vectors ; HL-60 Cells ; Humans ; Polymerase Chain Reaction ; Recombinant Proteins ; biosynthesis ; Sequence Analysis, DNA

In this paper,a number of valuable experiences focusing on teaching idea,cultivation of high-quality teachers and deepening of teaching content and method reform were summarized through exploring the construction and practice of the national excellent course-medical genetics. Aim of the ex-ploration is provide references for the construction and application of national excellent course and its sus-tainable development.

Objective To investigate the effect of arsenic trioxide on human coronary smooth muscle cells(HCSMCs). Method After the subculture of HCASMCs, cells were divided into 4 groups: control group and three arsenic trioxide (4.0 μmol/L) groups as the arsenic agent co-cultured with cells for 12,24 and 48 h. Flow cytometry and TUNEL were used for counting the ntmnber of cell apoptosis. RT-PCR was used to detect the expression of E2F-1 mRNA and Western blot was used to measure the levels of Bcl-2 ond Bax. Results Arsenic trioxide inhibited the proliferation of HCASMCs. When arsenic trioxide was 4.0 μmol/L, the living cells were ( 8.44 ±0.10) × 105/mL,signifiantly than that of control group (16.44 ± 1.34) × 105/mL, P ＜ 0.05. This inhibition of proliferation cycle was produced by affecting S and G2-M phase, which did not appear in the control group. Apoptotic cells increased from 16.0% ± 3.1% to 38.7% ± 2.7% (P ＜ 0.05) detected by TUNEL. The arsenic agnet decreased the Bcl-2 level and increased Bax. The expression of E2F-1 mRNA was decreased in 4.0 μmol/L arsenic trioxide group. Conclusions Arsenic trioxide exerts the apoptotic effect on human coronary smooth muscle cells.

Objective To investigate the apoptotic effects of arsenic trioxide on E2F-1 and EMAP-Ⅱ of hu-man coronary artery smooth muscle cells (HCASMCs). Method HCASMCs proliferated after culturing cells.Cells were divided into 4 groups: control group and arsenic trioxide (4.0μmol/L) 12 h group, 24 h group and 48 h group. Flow cytometry was used for counting number of apoptotic cells, RT-PCR was used for detecting the ex-pression of E2F-1 mRNA and Western blot was employed to get the level of EMAP-Ⅱ. Results Arsenic trioxide inhibited the proliferation of HCASMCs (living cells in 4.0 μmol/L arsenic trioxide were (8.44±0.10)×10~5/mL vs. control (16.44±1.34)×10~5/m (P <0.05), and the 4.0μmol/L arsenic trioxide inhibited proliferation cy-cle via affecting S and G2M phases, while those were not found in control group. E2F-1 mRNA expression was de-creased in 4.0 μmol/L arsenic trioxide group. Western blot test showed EMAP- Ⅱ level was also decreased in 4.0 μmol/L arsenic trioxide group. Conclusions Arsenic trioxide has apoptotic effect on smooth muscle cells of hu-man coronary artery and decrease the expression of E2F-1 mRNA and the level of EMAP- Ⅱ.