Triple-negative breast cancer cells respond to T cells severely at the alternative splicing layer

BACKGROUND: Cross talk of tumor­immune cells at the gene expression level has been an area of intense research. However, it is largely unknown at the alternative splicing level which has been found to play important roles in the tumor­immune microenvironment. RESULTS: Here, we re-exploited one transcriptomic dataset to gain insight into tumor­immune interactions from the point of AS level. Our results showed that the AS profiles of triple-negative breast cancer cells co-cultured with activated T cells were significantly changed but not Estrogen receptor positive cells. We further suggested that the alteration in AS profiles in triple-negative breast cancer cells was largely caused by activated T cells rather than paracrine factors from activated T cells. Biological pathway analyses showed that translation initiation and tRNA aminoacylation pathways were most disturbed with T cell treatment. We also established an approach largely based on the AS factor­AS events associations and identified LSM7, an alternative splicing factor, may be responsible for the major altered events. CONCLUSIONS: Our study reveals the notable differences of response to T cells among breast cancer types which may facilitate the development or improvement of tumor immunotherapy.

Clinical application of PD-1/PD-L1 to prognosis prediction and treatment of triple-negative breast cancer / 上海交通大学学报（医学版）

Programmed death-1 (PD-1) receptor and programmed death-ligand 1 (PD-L1) as a pair of T cell immune response co-stimulatory molecules play a negative role in adoptive immunity by inhibiting T lymphocyte function. Blocking the PD-1/PD-L1 signaling pathway has been a hot spot of research and treatment of cancer. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, and there is no approved targeted therapy. Immunotherapy represented by PD-1/PD-L1 blockers, is getting widely studied due to the medical potential of therapy for TNBC. Thereinto, the clinical researches of the monoclonal antibodies against PD-1 or PD-L1 have brought a promising future for the treatment of metastatic TNBC. Currently, there are several trials with anti-PD-1 or anti-PD-L1 monoclonal antibodies and their combination with other therapies in salvage, neoadjuvant, and adjuvant settings on going. In this article, the authors review the current studies about potential value of PD-1/PD-L1 in prognosis, prediction, and treatment in TNBC, intending to cast insight on future basic and clinical studies.

One stage three-column osteotomy for the treatment of scoliosis with split spinal cord malformation / 中国骨伤

OBJECTIVE@#To analyze the effectiveness and safety of one stage three column osteotomy in treatment of scoliosis with split spinal cord malformation.@*METHODS@#The clinical data of 41 patients with scoliosis and split spinal cord malformation underwent one-stage three-column osteotomy from January 2015 to December 2017 were retrospectively analyzed. There were 17 males and 24 females with average age of (25.14±4.51) years old and the average weight of (65.14±9.11) kg. According to the classification of longitudinal spina bifida, 15 cases of Pang typeⅠwere group A and 26 cases of Pang typeⅡwere group B. The general situations of two groups were recorded ; preoperative and postoperative Cobb angle were observed and the correction rate of Cobb angle of coronal plane was calculated ; the coronal and sagittal torso offset distances were compared between two groups and the trunk balance was evaluated ; the complication of two groups was recorded.@*RESULTS@#All 41 patients were followed up for more than 12 months. The operation time, intraoperative blood loss, and perioperative blood transfusion volume in group A were (610.14±115.02) min, (4 001.12±1 014.33) ml, (3 951.14±1 021.55) ml, respectively, and group B were (520.12±101.14) min, (2 701.57±1 021.45) ml, (2 565.77±880.47) ml, the difference between the two groups was statistically significant (0.05). There was no significant difference in postoperative coronary Cobb angle and correction rate between two groups (>0.05). Immediately after surgery and 12 months after surgery, there was no significant difference in the trunk displacement distance of coronal view and sagittal view between two groups (>0.05). Six patients in group A had complications, which was higher than that in group B of 1 case (=4.885, < 0.05).@*CONCLUSION@#One-stage three-column osteotomy in treatment of scoliosis with split spinal cord malformation has high correction rate and good balance of the trunk. However, for patients with typeⅠsplit spinal cord malformation, they will face longer operation time, more intraoperative bleeding volume, large amount of perioperative blood transfusion and higher risk of complications, and the safety is not as good as that of typeⅡpatients. Therefore, in the actual treatment of scoliosis, especially for those with typeⅠsplit spinal cord malformation, a more reasonable surgical plan should be developed in combination with the actual situations of the patients, so as to improve the safety of the operation.

Clinical Features of Relapsing Polychondritis Patients Presented with Arthropathy / 中国医学科学院学报

Objective To explore the clinical characteristics of relapsing polychondritis(RP)patients presented with arthropathy. Methods We retrospectively analyzed the clinical data of 201 RP patients who were hospitalized in our center between December 2005 and February 2019.After 16 patients with co-existing other autoimmune diseases and malignancies were ruled out,185 RP patients entered the final analysis,among whom 16 RP patients were presented with arthropathy and 169 without arthropathy.The demographic data,clinical manifestations,laboratory findings,and prognosis were compared between these two groups. Results Five of the 16 RP patients with arthropathy at presentation were misdiagnosed as rheumatoid arthritis.Compared with RP patients without arthropathy at presentation,RP patients with arthropathy at presentation had a longer disease course[(37.50±66.50)months

Survey on physicians who engage in cancer diagnosis and treatment from third-grade class A hospitals regarding the perceptions of cancer patients' fertility preservation / 上海交通大学学报（医学版）

Objective: To explore the perceptions and current practice barriers of Chinese physicians who engage in cancer diagnosis and treatment from third-grade Class A hospitals regarding cancer patients' perceptions of fertility preservation (FP). Methods: A study was conducted in physicians from 4 third-grade Class A hospitals with different clinical specialties assisting cancer patients through a structured self-report questionnaire between January 2017 and December 2017. A total of 179 medical oncologists, 77 radiation oncologists and 79 surgeons were included. Their information on gender, age, title, education background and perceptions of FP was obtained. Logistic regression analysis was used to examine the correlation between the recommendation of FP and risk factors. Results: There were 335 physicians, including 88 male physicians and 247 female physicians, with an average age of (35.94±6.27) years (range from 23-59 years) in the current study. Although 96.4% of the physicians knew that chemotherapy and radiation had a profound effect on impairment of fertility and 85.1% of them thought it was necessary to recommend FP, only 28.1% of them gave FP-related recommendations to the cancer patients. The oncologists and surgeons, female physicians, and those with higher professional titles and education background were more likely to make the FP recommendation. Among 63.3% of the physicians knowing male FP, only 37.9% and 21.2% of them noted the exact methods and place for FP, respectively. Similarly, for the 65.1% of the physicians knowing female FP, the percentage was 49.9% and 24.5%, respectively. When it came to the barriers of FP decision-making, 32.8% of the oncologists reported their concerns on whether cancer patients were suitable to reproduce. Secondly, the physicians honestly admitted that they lacked expertise in FP and worried about that FP would delay cancer treatment. Conclusion: Physicians who engage in cancer diagnosis and treatment lack the awareness and knowledge background of FP recommendation for cancer patients. It is important to improve the perceptions of cancer patients' FP through standardize training.

Survey on physicians who engage in cancer diagnosis and treatment from third-grade class A hospitals regarding the perceptions of cancer patients' fertility preservation / 上海交通大学学报（医学版）

Objective · To explore the perceptions and current practice barriers of Chinese physicians who engage in cancer diagnosis and treatment from third-grade Class A hospitals regarding cancer patients' perceptions of fertility preservation (FP).Methods · A study was conducted in physicians from 4 third-grade Class A hospitals with different clinical specialties assisting cancer patients through a structured self-report questionnaire between January 2017 and December 2017.A total of 179 medical oncologists,77 radiation oncologists and 79 surgeons were included.Their information on gender,age,title,education background and perceptions of FP was obtained.Logistic regression analysis was used to examine the correlation between the recommendation of FP and risk factors.Results· There were 335 physicians,including 88 male physicians and 247 female physicians,with an average age of (35.94±6.27) years (range from 23-59 years) in the current study.Although 96.4％ of the physicians knew that chemotherapy and radiation had a profound effect on impairment of fertility and 85.1％ of them thought it was necessary to recommend FP,only 28.1％ of them gave FP-related recommendations to the cancer patients.The oncologists and surgeons,female physicians,and those with higher professional titles and education background were more likely to make the FP recommendation.Among 63.3％ of the physicians knowing male FP,only 37.9％ and 21.2％ of them noted the exact methods and place for FP,respectively.Similarly,for the 65.1％ of the physicians knowing female FP,the percentage was 49.9％ and 24.5％,respectively.When it came to the barriers of FP decision-making,32.8％ of the oncologists reported their concerns on whether cancer patients were suitable to reproduce.Secondly,the physicians honestly admitted that they lacked expertise in FP and worried about that FP would delay cancer treatment.Conclusion· Physicians who engage in cancer diagnosis and treatment lack the awareness and knowledge background of FP recommendation for cancer patients.It is important to improve the perceptions of cancer patients' FP through standardize training.

Tet2 Regulates Osteoclast Differentiation by Interacting with Runx1 and Maintaining Genomic 5-Hydroxymethylcytosine (5hmC) / 基因组蛋白质组与生物信息学报·英文版

As a dioxygenase, Ten-Eleven Translocation 2 (TET2) catalyzes subsequent steps of 5-methylcytosine (5mC) oxidation. TET2 plays a critical role in the self-renewal, proliferation, and differentiation of hematopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Deletion of Tet2 impairs the differentiation of osteoclast precursor cells (macrophages) and their maturation into bone-resorbing osteoclasts in vitro. Furthermore, Tet2 mice exhibit mild osteopetrosis, accompanied by decreased number of osteoclasts in vivo. Tet2 loss in macrophages results in the altered expression of a set of genes implicated in osteoclast differentiation, such as Cebpa, Mafb, and Nfkbiz. Tet2 deletion also leads to a genome-wide alteration in the level of 5-hydroxymethylcytosine (5hmC) and altered expression of a specific subset of macrophage genes associated with osteoclast differentiation. Furthermore, Tet2 interacts with Runx1 and negatively modulates its transcriptional activity. Our studies demonstrate a novel molecular mechanism controlling osteoclast differentiation and function by Tet2, that is, through interactions with Runx1 and the maintenance of genomic 5hmC. Targeting Tet2 and its pathway could be a potential therapeutic strategy for the prevention and treatment of abnormal bone mass caused by the deregulation of osteoclast activities.

Risk factors and countermeasures for ERCP related duodenal papilla hemorrhage / 中国内镜杂志

Objective To investigate the risk factors and countermeasures for endoscopic retrograde cholangiopancreatography (ERCP) related duodenal papilla hemorrhage. Methods Retrospective analysis was performed on the clinical data of 890 patients who underwent ERCP. According to whether the patients with ERCP related duodenal papilla hemorrhage, they were divided into the hemorrhage group and the non hemorrhage group. And the risk factors of duodenal papilla hemorrhage and their countermeasures were investigated. Results 51 patients had ERCP related duodenal papilla hemorrhage, and the overall incidence rate was 5.7%. Compared with the non hemorrhage group, the patients proportion of common bile duct stones was lower, but the cholangiocarcinoma and pancreatic head cancer were higher in the hemorrhage group (P < 0.05). The incidence of hypertension and duodenal diverticulum in the hemorrhage group were significantly higher than that in the non hemorrhage group (P < 0.05). Subgroup analysis showed that patients with stone diameter >2 cm, stone incarceration and the duodenal papilla into diverticulum in the hemorrhage group were significantly higher than that in the non hemorrhage group (P < 0.05). Conclusion Common bile duct stone diameter >2 cm, stone incarceration, malignant biliary and pancreatic cancer, hypertension and duodenal papilla into diverticulum were objective risk factors of ERCP related duodenal papilla hemorrhage, focus on prevention of bleeding. Endoscopic hemostasis was safe and effective.

Role of Histone Methylation in Myeloid Malignancies -Review / 中国实验血液学杂志

Histone methylation is one of the important epigenetic regulatory mechanisms, and plays a significant role in a variety of physiological and pathological processes. Many recent studies have shown that abnormalities of histone methylation are closely related with the initiation and progression of myeloid malignancies. The reversibility of histone methylation provides a broad prospect for the discovery and application of specific small molecule drugs. This review summarizes the recent progresses in this area and mainly focuses on the correlation of histone methylation with myeloid malignancies.

Role of miR-206/CDK4 in modulating the growth and chemotlerapy sensitivity of ovarian cancer cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore role of miR-206 in modulating the growth and chemotherapy sensitivity in ovarian cancer cells.</p><p><b>METHODS</b>Real-time PCR was used to detect the expression of miR-206 in ovarian cancer and normal ovarian tissues. Ovarian cancer SKOV3 cells were transfected with a miR-206 mimic or a specific inhibitor of miR-206, and MTT assay and flow cytometry were used to detect the changes in cell growth and cell cycle transition. Western blotting and luciferase reporter gene assay were employed to identify the target gene and signal pathways of miR-206. The effect of miR-206 on the sensitivity of ovarian cancer cells to 5-Fu was assessed.</p><p><b>RESULTS</b>miR-206 was down-regulated in ovarian cancer tissues compared to normal ovarian tissues. Transfection of SKOV3 cells with the miR-206 mimic resulted in obvious growth suppression and delayed cell cycle transition from G1 to S phase by suppressing CDK4, c-Myc, and CCND1 expressions. Transfection with the miR-206 inhibitor obviously promoted the cell growth and significantly increased CDK4 expression in the cells. Luciferase reporter gene assay indicated that miR-206 could directly bind to the 3'UTR of CDK4 gene and reduce the activity of luciferase. Transfection of SKOV3 cells with miR-206 significantly lowered the ICof 5-Fu to enhance the chemotherapy sensitivity of the cells to 5-Fu.</p><p><b>CONCLUSION</b>As a potential tumor suppressor, miR-206 directly targets CDK4 to suppress the cell growth and enhance the chemotherapy sensitivity to 5-Fu in ovarian cancer cells in vitro.</p>

Risk factors and countermeasures for ERCP related duodenal papilla hemorrhage / 中国内镜杂志

Objective To investigate the risk factors and countermeasures for endoscopic retrograde cholangiopancreatography (ERCP) related duodenal papilla hemorrhage. Methods Retrospective analysis was performed on the clinical data of 890 patients who underwent ERCP. According to whether the patients with ERCP related duodenal papilla hemorrhage, they were divided into the hemorrhage group and the non hemorrhage group. And the risk factors of duodenal papilla hemorrhage and their countermeasures were investigated. Results 51 patients had ERCP related duodenal papilla hemorrhage, and the overall incidence rate was 5.7%. Compared with the non hemorrhage group, the patients proportion of common bile duct stones was lower, but the cholangiocarcinoma and pancreatic head cancer were higher in the hemorrhage group (P < 0.05). The incidence of hypertension and duodenal diverticulum in the hemorrhage group were significantly higher than that in the non hemorrhage group (P < 0.05). Subgroup analysis showed that patients with stone diameter >2 cm, stone incarceration and the duodenal papilla into diverticulum in the hemorrhage group were significantly higher than that in the non hemorrhage group (P < 0.05). Conclusion Common bile duct stone diameter >2 cm, stone incarceration, malignant biliary and pancreatic cancer, hypertension and duodenal papilla into diverticulum were objective risk factors of ERCP related duodenal papilla hemorrhage, focus on prevention of bleeding. Endoscopic hemostasis was safe and effective.

Comparison of the application of three different methods in the diagnosis of early diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To compare and analyze the diagnostic value of iris fluorescein angiography (IFA) combined with fundus fluorescein angiography (FFA),indocyanine green angiograph (ICGA),fundus fluorescein angiography in the diagnosis of early diabetic retinitis (DR).METHODS:Totally 70 patients (136 eyes) with early diabetic retinopathy enrolled in our hospital from August 2015 to August 2016 were selected in this study.All patients were respectively treated with ICGA,FFA and IFA+FFA,and the detection results of three kinds of imaging methods were analyzed.RESULTS:There were 120 pathological eyes (88.2％)were detected by FFA,124 pathological eyes (91.2％)were detected by ICGA,130 pathological eyes (95.6％)were detected by IFA+ FFA,and there was no significant difference in the detection rate between the three methods (P＞0.05).FFA detected 48 eyes with neovascularization,18 eyes with vitreous hemorrhage,38 eyes with macular edema,16 eyes without perfusion area;ICGA detected 49 eyes with neovascularization,38 eyes with macular edema,17 eyes with vitreous hemorrhage,20 eyes without perfusion area;IFA+ FFA detected 17 eyes with proliferative diabetic iridopathy (DI),22 eyes with non-proliferative DI,5 eyes with NVG,92 eyes without DI.CONCLUSION:In the diagnosis of early diabetic retinopathy,iris fluorescence angiography,fundus fluorescein angiography and indocyanine green angiography all have good diagnostic value,but IFA+FFA can detect the diabetic retinopathy in time and provide the help for the timely treatment.

Protective effect of epigallocatechin-3-gallate on hypoxia/reoxygenation injury in cardiac myocytes and its mechanism / 中国药理学通报

Aim To observe the protective effect of epigallocatechin-3-gallate (EGCG) on hypoxia/reoxygenation (H/R) injury of cardiac myocytes and its mechanisms.Methods H9c2 cardiac myocytes were cultured in vitro and randomly divided into five groups:normal group(N group),H/R group,EGCG low dose group (L group),EGCG medium dose group (M group),and EGCG high dose group(H group).The cardiomyocyte H/R injury model was established and EGCG was pretreated.Cell survival rate was tested by CCK-8 method.The cell apoptotic rate was detected using Annexin V-FITC/PI double staining.The contents of total antioxidant capacity(T-AOC) and tumor necrosis factor α(TNF-α) in cell culture medium were tested according to the kit instructions.The protein expression of Akt and p-Akt was observed using Western blot,while the gene expressions of PI3K,Akt,caspase3 were detected by using fluorescence quantitative PCR method.Results Compared with model group,EGCG increased cell survival rate and reduced the apoptosis after H/R injury.Meanwhile,pretreatment EGCG improved the activity of T-AOC,reduced the level of TNF-α,up-regulated the expression of PI3K,Akt and p-Akt,and down-regulated the expression of caspase3.Conclusion EGCG reduces apoptosis and protects cardiac myocytes by influencing PI3K/Akt signal path

Local application of different doses of tranexamic acid without drainage reduces blood loss after total knee arthroplasty / 中国组织工程研究

BACKGROUND: Total knee arthroplasty (TKA) is an effective method for the end-stage knee osteoarthritis, which can obviously relieve pain and improve function. But a large amount of postoperative blood loss is a serious complication, how to reduce postoperative blood loss is still a difficulty. OBJECTIVE: To explore the efficacy of local application of different doses of tranexamic acid without drainage on the METHODS: 150 patients with osteoarthritis who underwent TKA were randomly divided into three groups (n=50 per group). Group A received the intra-articular injection of tranexamic acid (2 g) plus 50 mL of normal saline; group B received the intra-articular injection of tranexamic acid (1 g) 50 mL of normal saline; group C received the intra-articular injection of 50 mL of normal saline. The drainage tube was not used in all patients. The number of hemoglobin, the number of patients undergoing blood transfusion, intraoperative blood loss, external blood loss, hidden blood loss, total blood loss and postoperative 3 hour-related blood coagulation indexes were recorded and compared among groups. Additionally, the incision infection and deep vein thrombosis were observed. RESULTS AND CONCLUSION: (1) The difference of hemoglobin among groups was significant (F=7.218-7.516, P=0.000).(2)The number of blood transfusion in the groups A,B and C was 2,5 and 9,respectively,which had significant differences (χ2=25.753, P=0.000). (3) The intraoperative blood loss had no significant difference among groups (F=1.206, P=5.283). The difference in the postoperative external blood loss, postoperative hidden blood loss and total postoperative blood loss among groups was significant (F=14.389, P=0.000; F=7.158, P=0.009; F=6.752, P=0.012). Moreover, the hemostatic effect was in a dose-dependent manner. (4) There were no significant differences in the postoperative 3-hour-related blood coagulation indexes among groups (P > 0.05). (5) There was no deep vein thrombosis at 1 week postoperatively, and no deep vein thrombosis or pulmonary embolism occurred within postoperative 3 months in the three groups. (6) To conclude, topical application of tranexamic acid without drainage can significantly reduce perioperative blood loss, blood transfusion rate, and does not increase the incidence of complications, and the hemostatic effect is in a dose-dependent manner.

Types of Organ Involvement in Patients with Immunoglobulin G4-related Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic disease that can involve multiple organs and various clinical phenotypes. The purpose of this study was to analyze different types of organ involvement in IgG4-RD patients in China.</p><p><b>METHODS</b>We conducted a prospective cohort study on IgG4-RD patients to analyze the clinical manifestations and rare features of IgG4-RD. Patients were grouped into different types according to organ involvement regarding organ number and organ site. The constituent ratio in different types was also analyzed.</p><p><b>RESULTS</b>A total of 200 IgG4-RD patients, with a male:female ratio of 2.08:1, were grouped into different types. Cases having involvement of two or three organs were the most common whereas the fewest number of patients had multi-organ (≥4) involvement. Serum IgG4 and IgE levels, IgG4/IgG ratio, and percentage of eosinophils increased as the number of involved organs increased. In addition, constituent ratio analysis revealed that patients with salivary gland/lacrimal gland swelling, who also constituted the largest number of IgG4-RD patients, had higher serum IgG4 concentrations and IgG4/IgG values, had higher percentage of Eos, and were more likely to have had a history of allergies relative to patients with internal organ involvement.</p><p><b>CONCLUSIONS</b>The characteristic feature of IgG4-RD is multiple organ involvement with various clinical manifestations and different types. Although serum IgG4 levels increased with the number of involved organs, serum IgG4 levels were higher for those patients with salivary gland/lacrimal gland swelling compared with those with internal organ involvement. Thus, valuable clues to the differential diagnosis of IgG4-RD could be obtained by examining the clinical patterns of organ involvement.</p>

Diagnostic Value of T-cell Interferon-γ Release Assays on Synovial Fluid for Articular Tuberculosis: A Pilot Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tuberculosis (TB) remains a major global public health challenge. Articular TB is an important form of extrapulmonary tuberculosis, and its diagnosis is difficult because of the low sensitivity of traditional methods. The aim of this study was to analyze the diagnostic value of T-SPOT.TB on synovial fluid for the diagnosis of articular TB.</p><p><b>METHODS</b>Patients with suspected articular TB were enrolled consecutively between August 2011 and December 2015. T-SPOT.TB was performed on both synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs). The final diagnosis of articular TB was independent of the T-SPOT.TB result. The diagnostic sensitivity, specificity, predictive value, and likelihood ratio of T-SPOT.TB on SFMCs and PBMCs were analyzed.</p><p><b>RESULTS</b>Twenty patients with suspected articular TB were enrolled. Six were diagnosed with articular TB, and 14 patients were diagnosed with other diseases. Sensitivity and specificity were 83% and 86% for T-SPOT.TB on SFMCs, and 67% and 69% for T-SPOT.TB on PBMCs, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of T-SPOT.TB on SFMCs were 71% and 92%, respectively. The PPV and NPV were 50% and 82% for T-SPOT.TB on PBMCs.</p><p><b>CONCLUSION</b>Sensitivity, specificity, and NPV of T-SPOT.TB on SFMCs appeared higher than that on PBMCs, indicating that T-SPOT.TB on SFMCs might be a rapid and accurate diagnostic test for articular TB.</p>

Association Study of a Proliferation-inducing Ligand, Spermatogenesis Associated 8, Platelet-derived Growth Factor Receptor-alpha, and POLB Polymorphisms with Systemic Lupus Erythematosus in Chinese Han Population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. This study was conducted to examine whether the association of a proliferation-inducing ligand (APRIL), spermatogenesis associated 8 (SPATA8), platelet-derived growth factor receptor-alpha (PDGFRA), and DNA polymerase beta (POLB) with SLE can be replicated in a Chinese Han population.</p><p><b>METHODS</b>Chinese SLE patients (n = 1247) and ethnically and geographically matched healthy controls (n = 1440) were genotyped for the APRIL, SPATA8, PDGFRA, and POLB single-nucleotide polymorphisms (SNPs), rs3803800, rs8023715, rs1364989, and rs12678588 using the Sequenom MassARRAY System.</p><p><b>RESULTS</b>The Chinese Han SLE patients and controls had statistically similar frequencies of alleles and genotypes of four gene polymorphisms. Moreover, no association signal was detected on different genetic models (additive, dominant, and recessive, all, P> 0.05) or in SLE subgroups stratified by various clinical manifestations (all, P> 0.05).</p><p><b>CONCLUSIONS</b>Different genetic backgrounds from different ancestries and various populations may result in different genetic risk factors for SLE. We did not detect any significant association with SNPs of APRIL, SPATA8, PDGFRA, and POLB.</p>

Expression of CDK6 in early ovarian cancer and its clinical significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the expression of CDK6 in early ovarian cancer and explore its clinical significance.</p><p><b>METHODS</b>Real-time PCR and immunohistochemistry was used to examine the differential expression of CDK6 mRNA and protein in ovarian cancer and normal ovarian tissues. The correlation of CDK6 expression with the clinical characteristics and prognosis of the patients was analyzed.</p><p><b>RESULTS</b>The expression of CDK6 mRNA was obviously up-regulated in 36 ovarian cancer tissues as compared to that in 16 ovarian tissues. Immunohistochemistry demonstrated that CDK6 protein was expressed in both the cytoplasm and cell nuclei. Compared with the 48 normal ovarian tissues, the 121 ovarian cancer tissues showed significantly up-regulated CDK6 protein expression (P=0.044). Increased CDK6 protein expression was not significantly correlated with the clinical features of the patients with ovarian cancer, but showed a significant negative correlation with the patients' prognosis (P=0.006). Multivariate analysis suggested that CDK6 expression level was an independent prognostic indicator (P=0.008) for the survival of patients with ovarian cancer.</p><p><b>CONCLUSION</b>Increased CDK6 protein expression may promote the development and progression of early ovarian cancer.</p>

Research Advances in the Mutation of TET2 Gene in Myeloid Maligancies / 中国医学科学院学报

TET2 gene is a member of TET oncogene family. It has been reported as a tumor suppressor gene with important roles in myelopiesis. Recent studies have shown that TET2 protein takes part in demethylation by converting 5-methylcytosine (5-mc) into 5-hydroxymethylcytosine (5-hmc). Somatic TET2 inactivation leads to abnormal myelopiesis and myeloid malignancies. In this review,the structure and function of TET2 and the relationship between TET gene mutation and myeloid malignancies are summarized.

In vitro activity of a novel cannabinoid receptor l selective antagonist LMJ07 / 国际药学研究杂志

Objective: LMJ07 is a novel cannabinoid receptorl (CB1R) selective antagonist discovered by our lab. In the present study, its affinity and antagonistic activity against CB1R were evaluated at the molecular and cellular levels by receptor binding experiment, CB1R internalization experiment and by monitoring the change in cytoskeletal and intracellular signal induced by CB1R activation. Methods: With the CB1R selective antagonist rimonabant (SR141716A) as control, the affinity and selectivity of LMJ07 to CB1R and CB2R were assayed by radioligand binding assays, and the G protein-independent antagonistic activity against cannabinoid receptor (CBR) was assayed by enhanced green fluorescein protein (EGFP)-CBR internalization with hierarchiae cluscer anclysis (HCA) analysis. At the same time, we evaluated the changes in cytoskeletal and the intracellular cAMP levels in response to LMJ07 treatment in CHO-CB1 cells by Cellkey label-free assays and homogeneous time-resolved fluorescence (HTRF). Additionally, we also confirmed the CB1R antagonistic efficacy of LMJ07 by detecting the content of Ca2+ in primary cultured hippocampal neuronal cells which could express CB1R with continuous fluorescence detection technology. Results: LMJ07 is a selective CB1R antagonist with high affinity, which can selectively antagonize receptor endocytosis induced by CB1RactivationIt’s affinity and antagonistic efficacy to CB1R were equal to those of rimonabant. In CHO-CB1 cells, LMJ07 (0.01-10μmol/L)could dose-dependently inverse the change in cytoskeletal as well as the increase in intracellular cAMP induced by CBR agonist Win55212-2. In the primary cultured hippocampal neuronal cells, LMJ07 (10 nmol/L-1 μmol/L) could block the increase in [Ca2+] induced by CB1R agonist Win55212-2. Conclusion: LMJ07 is a new selective CB1R antagonist, which shows equal affinity and antagonistic activity against CB1R as the widely accepted CB1R antagonist rimonabant. In addition, the combination of high content analysis (HCS) and Cellkey label-free assay provides a better research tool for rapid and high throughput screening of novel CB1R antagonists.