The Ubiquitin Ligase SMURF1 Catalyzes the Polyubiquitination of ADAR1 / 中国生物化学与分子生物学报

It is known that SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) mediates autophagy through its E3 ubiquitin ligase activity, but the ubiquitinated substrates of SMURF1 need to be further explored. In this paper, the interacting proteins of SMURF1 in THP-1 cells were captured and identified by co-immunoprecipitation (Co-IP) combined with mass spectrometry. It was found that SMURF1 could physically bind to 222 proteins in THP-1 cells, and Adenosine deaminase acting on RNA 1 (ADAR1) had a higher peptide binding score. SMURF1 overexpression vectors were constructed and transfected into HEK-293T cells, then Co-IP and Western blotting assays verified the interaction between exogenous SMURF1 and endogenous ADAR1. qRT-PCR and Western blotting assays were carried out after transfecting SMURF1 overexpression vectors in HEK-293T cells, which identified that overexpression of SMURF1 attenuated the protein levels of ADAR1 (P<0. 05). However, there was no significant difference in the mRNA level of ADAR1. HEK-293T cells with normal and overexpressing SMURF1 were treated with cycloheximide (CHX), respectively, and Western blotting assays showed a shortened half-life of ADAR1 after overexpression of SMURF1 (P < 0. 05). Furthermore, overexpression of SMURF1 increased the polyubiquitination level of ADAR1 as detected by Co-IP and Western blot (P<0. 05). After the proteasome inhibitor (MG132) treatment, the Western blotting assay was performed to demonstrate that the negative regulatory effect of SMURF1 on ADAR1 was weakened after the proteasome degradation pathway was attenuated (P<0. 05). This study shows that SMURF1 interacts with ADAR1, catalyzes the polyubiquitination of ADAR1 and mediates its degradation through the proteasome pathway, which provides a theoretical basis for exploring the various biological functions of SMURF1 by affecting the stability of ADAR1.

Aesthetic reconstruction of the scar contracture deformity in chin and neck with expanded flaps based on the "MRIS" principle / 中华烧伤杂志

Objective: The surgical reconstruction strategy for scar contracture deformity in chin and neck was explored, aiming to obtain better aesthetic outcome. Methods: A retrospective observational study was conducted. From December 2017 to April 2021, 34 patients with scar contracture deformity in chin and neck after burns were hospitalized in the Department of Plastic Surgery of the First Affiliated Hospital of Army Medical University (the Third Military Medical University), aged 12-54 years, including 13 males and 21 females, 4 cases with chin affected only, 7 cases with neck affected only, and 23 cases with both chin and neck affected. The scar areas were 48-252 cm2. All the patients were treated by operation with expanded flaps, following the "MRIS" principle of matching of the color and thickness of the repair flaps (match), reconstructing of the aesthetic features of subunits (reconstruction), design of incision according to the plastic principle (incision), and prevention of the surgical incision scar (scar). The rectangular or kidney shaped skin and soft tissue expander (hereinafter referred to as the expander) with rated capacity of 80-400 mL was embedded in the first stage, which was routinely expanded to 3-5 times of the rated capacity of the expander. In the second stage, scar resection and expanded flap excision were performed to repair the secondary wound, and the flap donor site was sutured directly. The expansion ratio of the expander (with average value being calculated), the type of flaps used, the reconstruction of local aesthetic morphology, the appearance of postoperative incision, the survival of flap, and the situation of donor and recipient sites observed during follow-up were recorded. Results: Among the 34 patients, the average expansion ratio of the implanted expander was 3.82 times of the rated capacity of the expander. Three cases were repaired by the expanded local pedicled flap only, 19 cases by the expanded shoulder and/or chest perforator pedicled flap only, 10 cases by the expanded local pedicled flap combined with the expanded shoulder and/or chest perforator pedicled flap, and 2 cases by the expanded local pedicled flap combined with the expanded free flap of the second intercostal perforator of internal thoracic artery. After scar resection, the shapes of lower lip and chin-lip groove were reconstructed in 10 cases, chin process reconstruction and chin lengthening were performed in 16 cases, and the cervico-mental angle and mandibular margin contour were reconstructed in 28 cases. The surgical incision was concealed, most of which were located at the natural junction or turning point of the chin and neck subunits. The vertical incision of neck was Z-shaped or fishtail-shaped. All the expanded flaps in 34 patients survived after operation, of which 8 patients had minor necrosis at the edge or tip of the expanded flaps 1-3 days after operation and healed after dressing change. During the follow-up of 3-18 months, little difference in color and thickness between the expanded flap and the skin of chin and neck was observed, and the aesthetic shape of chin and neck was significantly improved, with mild scar hyperplasia of surgical incision. Conclusions: Reconstruction of scar contracture deformity in chin and neck by using expanded flaps based on the "MRIS" principle is beneficial to improve the quality of surgery and achieve better aesthetic outcome.

Effects of SMILE and FS-LASIK on early postoperative corneal higher order aberrations in patients with high myopia / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the effects of small-incision lenticule extraction(SMILE)and femtosecond laser-assisted excimer laser <i>in situ</i> keratomileusis(FS-LASIK)on early postoperative corneal higher order aberrations(HOAs)and visual quality in patients with high myopia. <p>METHODS:Totally 102 patients(204 eyes)with high myopia who underwent corneal refractive surgery between August 2018 and August 2020 in the hospital were selected as study subjects for the prospective study, and they were randomly divided into SMILE group(51 cases, 102 eyes)and FS-LASIK group(51 cases, 102 eyes). The postoperative visual acuity, corneal HOAs and objective visual quality were compared between the two groups, and the correlation between corneal HOAs and objective visual quality was analyzed. <p>RESULTS: At 1mo after surgery, the spherical equivalent degrees in SMILE group and FS-LASIK group were significantly reduced(<i>P</i><0.05), and there was no statistically significant difference in the proportion of patients with postoperative uncorrected visual acuity≥preoperative best corrected visual acuity between the two groups(95.1% <i>vs</i> 92.2%, <i>P</i>>0.05). The corneal HOAs in the two groups were significantly increased(<i>P</i><0.05), and the overall spherical aberration(SA), trefoil and higher HOAs in SMILE group were lower than those in FS-LASIK group(all <i>P</i><0.05). The objective scattering index(OSI)was significantly increased in the two groups while the MTF cutoff frequency(MTF_cutoff), Strehl Ratio(SR)and contrast visual acuity(VA100%, VA20%, VA9%)were significantly decreased(all <i>P</i><0.05). The OSI of SMILE group was lower than that of FS-LASIK group while MTF_cutoff and VA9% were higher than those of FS-LASIK group(all <i>P</i><0.05). The corneal HOAs in patients with high myopia were negatively correlated with MTF_cutoff and were positively correlated with OSI(<i>P</i><0.05).<p>CONCLUSION:Both SMILE and FS-LASIK can effectively correct high myopia, and SMILE has a smaller increase in early postoperative corneal HOAs, and it is of great significance to relieve visual quality impairment.

Soluble receptor for advanced glycation end-products inhibits myocardial fibrosis of ischemia/reperfusion mice / 解剖学报

Objective To investigate the effect of soluble receptor for advanced glycation end-products (sRAGE) on inflammation in myocardial ischemia/reperfusion ( I/R ) mice and its mechanism. Methods Myocardial I/R injury model was conducted by left anterior descending ligation for 30 minutes and reperfusion for 2 weeks in male C57BL/6 mice aged 6-8 weeks. The mice were randomly divided into four groups with five C57BL/6 mice in each group. The cardiac function was detected by echocardiography, the inflammatory cells infiltration was observed by HE staining, the myocardial fibrosis was detected by Masson and Sirius red staining, the expression of galectin-3 was detected by immunohistochemical staining. Results Compared with the sham group, the cardiac function decreased, the inflammatory cells infiltrated increased among the myocardial tissue, the percentage of myocardial fibrosis area increased, and the expression of galectin-3 increased in I/R groups. After exogenous sRAGE treatment, the cardiac function of mice was significantly improved, the inflammatory cells infiltration decreased, the myocardial fibrosis area decreased, and the expression of galectin-3 decreased as well. Conclusion sRAGE may reduce inflammatory cells infiltration in mice heart by inhibiting the expression of galectin-3, and then alleviating myocardial fibrosis during myocardial ischemia/reperfusion injury.

Correlation factor analysis of poor prognosis in patients with acute solitary pontine infarction / 临床神经病学杂志

Objective To analyze the influence factors of poor prognosis in acute solitary pontine infarction. Methods The maximal diameter of the infarct lesion, arterial blood supply distribution and perforating artery atherosclerosis in 73 acute solitary pontine infarction patints were examined by brain MRI. The intracranial vascular stenosis was assessed by brain MRA or CTA. Carotid ultrasound was used to evaluate the atherosclerosis of extracranial artery. According to the mRS score, patients were divided into poor prognosis group ( mRS score≥3) and good prognosis group ( mRS score <3). Results Compared with those in good prognosis group, the rate of diabetes, admission and discharge NIHSS score, early progress rate, fasting blood glucose level in poor prognosis group were significantly higher,and the ratio of males was significantly lower (P<0. 05 -0. 01). Compared with those in good prognosis group, incidence of infarction with multiple blood supply, perforators atherosclerosis, vertebral basilar artery stenosis ratio and maximum diameter of infarction in poor prognosis group were significantly higher (all P<0. 01). The lesion which extended from the deep part of the pontine to the ventral side of the pontine and basilar artery stenosis were independent predictors of poor prognosis in patients with acute solitary pontine infarction (OR=22. 137, 95% CI:2. 563 -191. 228, P=0. 005; OR=28. 552, 95% CI:2. 347 -347. 313, P=0. 009). Conclusion Perforating artery atherosclerosis and basilar artery stenosis are independent predictors of poor prognosis in patients with acute solitary pontine infarction.

The expression and clinical importance of Reg IV in different molecular subtypes of breast cancer / 医学研究生学报

Objective RegIV, which is the latest member of the regenerative gene family, has been found to be closely related to the development of various tumors, but rarely reported in invasive breast cancer. This article is intended to explore the expression levels of regenerative factor 4(regeneration islet-derived family, member 4, RegIV), and the correlation with clinicopathological features and prognosis in 4 molecular subtypes of breast cancer(LA, LB,HER-2+, TNBC). Methods Pathological data of 284 breast cancer patients from March 2011 to October 2017 in the department of pathology, Lianyungang first people’s hospital were collected. To analyze the expression of RegIV in different molecular subtypes (LA, LB, HER-2+, TNBC) and its relationship with clinicopathological features, we analyzed the expression level of RegIVmRNA in breast cancer and its prognosis of patients. Results The positive rates of Reg IV in Luminal A group, Luminal B group, HER-2 positive group and triple negative breast cancer were 52.11%（37/71）, 50.00%（42/84）, 65.22%（45/69）and 20.00%（12/60）,which was statistically significant when comparing them in pairs(P<0.01). The expression of RegIV was associated with tumor diameter, lymph node metastasis, TNM stage(P<0.01). The recurrence risk of breast cancer patients with high RegIV expression was lower than those with low RegIV expression (HR=0.59,95%CI:0.50-0.69). Further analysis found that the recurrence risk of LA breast cancer patients with high RegIV expression (HR=0.63,95%CI:0.48-0.82), and so it was with LB(HR=0.56,95%CI:0.40-0.76) and TNBC(HR=0.51,95%CI:0.36-0.71). Conclusion RegIV can provide reference for molecular subtypes diagnosis and it may be one of the indicators to evaluate the prognosis of breast cancer patients.

Expression of monocyte chemoattractant protein-1 in aqueous humor of patients with primary acute angleclosure glaucoma and its association with the patients' prognosis after trabeculectomy / 眼科新进展

Objective To measure the levels of monocyte chemoattractant protein-1 (MCP-1) in the aqueous humor of patients with acute primary angle-closure glaucoma (APACG),and its correlation with the patients' prognosis after trabeculectomy.Methods This retrospective case-control study included 19 patients with APACG who experienced a failed trabeculectomy (case group) and 57 age-and sex-matched patients with APAGG who underwent successful trabeculectomy (control group).Aqueous humor was collected before trabeculectomy for the detection of MCP-1 levels in the both groups by enzyme-linked immunosorbent assay.And finally,logistic regression analysis was applied to assess the risk factors for failed trabeculectomy.Results The MCP-1 concentration in aqueous humor was (5688.04 ± 2099.99)ng · L-1 in the case group and (2077.57 ± 568.44)ng · L-1 in the control group,and the difference between both groups were significant (P ＜ 0.001).Logistic regression analysis revealed MCP-1 level (OR =1.005;95％ CI =1.001-1.008) and a shallow anterior chamber after surgery (OR =31.430;95％ CI =1.577-57.350) were the independent risk factors for failed trabeculectomy procedures.Conclusion MCP-1 levels in aqueous humor are higher in APACG eyes with failed trabeculectomy than those with successful one during 1-year follow-up,so MCP-1 level is considered as an independent risk factor for failed trabeculectomy.

Expression and clinical pathological significance of the five types heavy chain of Ig protein in mucosa-associated lymphoid tissue lymphoma / 临床与实验病理学杂志

Purpose To investigate the expression of the heavy chain of Ig protein, and observed it's value on differential diagnosis and significance on clinical pathological. Methods50 cases of non-Hodgkin's lymphoma (NHL) were collected as experimental group, including 30 cases of MALToma, 10 cases of follicular lymphoma (FL), and 10 cases of plasmacytoma(PC), 10 cases of reactive lymphoid hyperplasia (RLH) were collected as control group. The expression of IgM, IgA, IgD, IgG and IgE were detected by immunohistochemistry in the two groups. Results The lower positive rates of IgM, IgA were observed in the experimental group, MALToma, PC, and the lower positive rates of IgG, IgA were observed in FL (P＜ 0.05 ). The positive rate and expression intensity of IgM showed a rising trend (P＜ 0.05), and the positive rate of IgG show a downward trend (P＞0.05) in FL, MALToma, PC. There were three patterns of the heavy chain expression in the two groups: a single type expression, all negative expression, and a various type expression. The positive rates of a single type/ all negative heavy chain expression were 86.7％, 60％, 80％, 0 respectively in MALToma, FL, PC and RLH, the differences were statistically significant (P＜ 0.05 ). The positive rate of IgG was related to the type of tumor cells in MALToma(P＜ 0.05 ). Conclusion The expressions of IgM and IgG show a contrast trend in FL, MALToma, PC, and support that the most of MALToma and PC which come from postgerminal center experience class switch recombination, and frequently express a single IgG. A single type/all negative heavy chain expression is a frequent event in the MALToma, and it's helpful to the differential diagnosis of MALToma and RLH.

Analysis of clinical features and prognostic factors of desmoplastic small round cell tumor / 上海交通大学学报（医学版）

Objective·To analyze the clinical features and prognostic factors of desmoplastic small round cell tumor (DSRCT). Methods·Clinical datum of 140 patients with DSRCT published from Nov. 2003 to Jul. 2012 were collected and studied retrospectively by searching Medline and Embase databases. The observation indicators were progression-free survival (PFS) or overall survival (OS). Survival rates were calculated using the Kaplan-Meier method and compared between groups using a log-rank test. Multivariate analysis was performed using the Cox model to determine the prognostic factors. Results·Patient median age was (23.2±12.7) years (range 4-74 years, the ratio of male and female was 3.12:1). Frequent symptoms were abdominal pain (35.7%) and evidence of a palpable mass (20.0%). 106 cases tumors were in the abdominal or pelvic cavity, the remaining were extra-abdominal tumors. The frequency of patients receiving conventional chemotherapy, cytoreductive surgery, neoadjuvant chemotherapy, adjuvant chemotherapy or first-line chemotherapy was 76.4%, 52.1%, 17.1%, 47.9% and 38.6%, respectively. Some patients received adjuvant radiotherapy (17.1%), hyperthermic intraperitoneal chemotherapy (4.1%) and bone marrow transplantation (7.3%). By univariate analysis, male gender, absence of metastasis, effective cytoreductive surgery, chemotherapy and multimodal therapy were significant prognostic factors for prolonged OS (all P<0.05). Primary tumor site, extra-abdominal tumors, absence of metastasis and effective cytoreductive surgery were associated with improved PFS (all P<0.05). Cox regression analysis showed effective cytoreductive surgery and chemotherapy were independent prognostic factors. Conclusion·Multimodal therapeutics that clear tumors by surgery, adjuvant therapy are favorable prognostic factors for improved survival level in DSRCT patients.

Clinical and Pathologic Features of Myeloid Sarcoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the clinicopathologic features, differential diagnosis and therapy of myeloid sarcoma.</p><p><b>METHODS</b>The clinical data including clinical manifestations, laboratorial tests, histopathologicical examination, immunohistochemistry and clinical prognosis of 10 patients with myeloid sarcoma were analyzed retrospectively. Among 10 patients, 5 male and 5 female, aged 23 to 71 years old (median = 36 years).</p><p><b>RESULTS</b>2 cases of myeloid sarcoma were secondary from chronic myeloid leukemia, and 1 cases of myeloid sarcoma occurred after the allogeneic hematopoietic stem cell transplantation due to acute myeloid leukemia, and the others lacked the anamnesis of malignancies. The neoplasms occurred at bone, brain, skin, breast, epididymis, uterine cervix, small intestine, ovary and lymph nodes. Microscopically, the tumor cells were round or oval, which infiltrated diffusely or arranged in single-file. The cytoplasm was scarce and immature eosinophils were scattered. The nuclei were round, oval or focally irregular, and the mitosis was visible. The neoplasms were positive for MPO, CD34, CD43, CD45, CD99 and CD117 by immunohistochemical staining. 4 patients progressed into acute myeloid leukemia from 2 to 10 months after the diagnosis of myeloid sarcoma. All of them achieved complete remission after inductive chemotherapy, but 3 patients relapsed from 3 to 12 months after remission and only survived for 14 to 23 months. 4 patients were treated by using chemotherapy before bone marrow abnormality, and with the disease-free survival for 1 to 48 months.</p><p><b>CONCLUSION</b>Myeloid sarcoma needs to be distinguished from lymphoblastic lymphoma, Burkitt's lymphoma, blastic plasmacytoid dendritic cell neoplasms and so on. The diagnosis and differential diagnosis of myeloid sarcoma are dependent on the pathological and immunohisto-chemical features. The chemotherapy and allogeneic hematopoietic stem cell transplantation of acute myeloid leukemia are the main methods for treatment of myeloid sarcoma.</p>

Clinicopathologic characteristics and reticular fiber staining of adrenocortical carcinoma / 临床与实验病理学杂志

Purpose To analyse the clinicopathologic characteristics and reticular fiber staining of adrenocortical carcinoma (ACC).Methods The clinical,imaging,pathological data and reticular fiber staining of 20 cases with adrenocortical adenoma (ACA) and 16 cases with ACC were analyzed retrospectively.Results The median course of disease and maximum diameter of ACA were 21 months and 2.6 cm respectively,but ACC were 5 months and 9.5 cm respectively.9 cases with ACC were diagnosed with distant metastasis.Histologically,ACA cells arranged in nest-like and coarse trabecular forms with acidophilic or clear cytoplasm,unconspicuous nuclear atypia,and rare mitotic figures.The capsules,sinusoids and veins were uninvolved,and hemorrhage,necrosis and thick collagen fibers were infrequent.The Weiss score of all ACA was less than 2 (average =0.85 ± 0.81).ACC cells arranged in nest-like,coarse trabecular,cord-like,and diffuse structure with acidophilic cytoplasm,various nuclear atypia and atypical mitotic figures.The invasion of capsules,sinusoids and veins,hemorrhage and necrosis regions and thick collagen fibers were easily found.The Weiss score of all ACC was more than 3 (average =5.2 ±1.3).Immunohistochemical staining showed that vimentin,Syn,NSE,CK,CR,Melan-A and α-inhibin were expressed similarly between ACA and carcinoma (P ＞ 0.05).Reticular fiber staining revealed that the reticular fiber structures of ACA were unbroken,but ACC were destructed with various degrees of rupture,collapse,sparsity or disappearance (P ＜ 0.01).Conclusion ACC lacks characteristic immune phenotype,but increased diameter,distant metastasis,thick collagen fibers and destructed reticular fibrillar network are helpful in the diagnosis of ACC.

Mutation Analysis of MR-1, SLC2A1, and CLCN1 in 28 PRRT2-negative Paroxysmal Kinesigenic Dyskinesia Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Paroxysmal kinesigenic dyskinesia (PKD) is the most common subtype of paroxysmal dyskinesias and is caused by mutations in PRRT2 gene. The majority of familial PKD was identified to harbor PRRT2 mutations. However, over two-third of sporadic PKD patients did not carry anyPRRT2 mutation, suggesting an existence of additional genetic mutations or possible misdiagnosis due to clinical overlap.</p><p><b>METHODS</b>A cohort of 28 Chinese patients clinically diagnosed with sporadic PKD and excluded PRRT2 mutations were recruited. Clinical features were evaluated, and all subjects were screened for MR-1, SLC2A1, and CLCN1 genes, which are the causative genes of paroxysmal nonkinesigenic dyskinesia (PNKD), paroxysmal exertion-induced dyskinesia, and myotonia congenita (MC), respectively. In addition, 200 genetically matched healthy individuals were recruited as controls.</p><p><b>RESULTS</b>A total of 16 genetic variants including 4 in MR-1 gene, 8 in SLC2A1 gene, and 4 in CLCN1 gene were detected. Among them, SLC2A1 c.363G>A mutation was detected in one case, and CLCN1 c.1205C>T mutation was detected in other two cases. Neither of them was found in 200 controls as well as 1000 Genomes database and ExAC database. Both mutations were predicted to be pathogenic by SIFT and PolyPhen2. The SLC2A1 c.363G>A mutation was novel.</p><p><b>CONCLUSIONS</b>The phenotypic overlap may lead to the difficulty in distinguishing PKD from PNKD and MC. For those PRRT2- negative PKD cases, screening of SLC2A1 and CLCN1 genes are useful in confirming the diagnosis.</p>

Relationship between Electroencephalogram and Perceived Stress in Essential Hypertension Patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the relationship between electroencephalogram and perceived stress in Chinese essential hypertension (EH) patients.</p><p><b>METHODS</b>Totally 60 EH patients were enrolled as the case group,and 60 gender-and age-matched healthy subjects as the control group. Graded mental arithmetic was used as a psychological stressor. The physiological values of electroencephalogram (Theta,Alpha,sensorimotor rhythm,and Beta) were recorded at baseline and in mission period and recovery period. Subjects were instructed to complete the Perceived Stress Scale.</p><p><b>RESULTS</b>The electroencephalogram Theta value was significantly different between the case group and the control group (t=4.01,P=0.048). In the case group,the fluctuating Theta value was correlated with the control dimension in the Perceived Stress Scale (r=-0.26,P=0.044). Also in the case group,with the score of "sense of control" as the dependent variable and the fluctuating value of Theta after stress as the independent variables,regression analysis was performed. The opt-in standard was≤0.05 and the culling standard was≥0.01. The Results shows that the fluctuating value of Theta after stress in the case group met the requirements to enter the equation and could explain 5.2% of "sense of control" dimension.</p><p><b>CONCLUSION</b>The Theta values associated with the sleeping and creativity decrease under stressful situations in EH patients following the increaed sense of pressure due to failure in controlling the pressure events.</p>

Progress in chemical proteomics-based kinome study / 国际药学研究杂志

Protein kinases are key components of cell signaling networks and thereby regulate fundamental biological processes such as cellular growth, proliferation, metabolism and survival. Kinome refers to all kinases in cells or tissue and "kinomics" is the global analysis of kinome with respect to abundance, activity, substrate specificity, phosphorylation pattern and mutational status. Human kinome currently contains 568 members, nearly half of which can be mapped to disease loci and deregulation of kinase activity by gene amplification or mutations has been implicated in diseases such as inflammation, diabetes and cancer. Therefore, human kinome is being recognized as a potentially rich source of drug targets. Kinase inhibitors have been successfully used to treat many kinds of advanced cancers. Chemical proteomics is emerging as a novel comprehensive kinome approach that combines an immobilized inhibitor affinity pull-down approach with mass spectrometry-based proteomics for kinase identification, quantification and phosphorylation analysis under physiological condition. Commonly, one or multiple broad-spectrum kinase inhibitors are covalently immobilized on a biocompatible matrix such as sepharose to enrich all kinases in cells or tissue and then the kinases are identified and quantified by mass spectrometry analysis. It can be used to study the specificity of kinase inhibitor drug, drug candidate or drug resistance mechanism, which can help to understand the mechanism and find combinational drug target. Large-scale unbiased kinome and cancer kinome study will facilitate new drug target discovery and correlate tumor tissue kinome profiles with response to therapy and therefore may be used for future therapy selection in personalized medicine. In this paper, the human kinome, kinase, kinase inhibitor and cancer, chemical proteomics based kinome study progress and its applications in drug discovery are reviewed.

Clinical study on the treatment of abnormal blood lipids complicated with carotid atherosclerosis with lipid-reducing red rice minute powder: a randomized controlled trial / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the clinical effects of lipid-reducing red rice minute powder (LRRMP) on the levels of blood lipids, carotid artery intima-media thickness (IMT), and the plaque integral of hyperlipidemia patients complicated with carotid atherosclerosis.</p><p><b>METHODS</b>This study was conducted from April 2005 to April 2006 according to inclusion criteria. Sixty hyperlipidemia patients complicated with carotid atherosclerosis were randomly assigned to the treatment group (20 cases), the Chinese medicine control group (CM control group, 20 cases), and the Western medicine control group (WM control group, 20 cases). They were recruited from the community of secondary machine tool factory of Jinan. Patients in the treatment group took LRRMP (175 mg/pill), one pill each time, twice daily. Patients in the CM control group took Xuezhikang Capsule (300 mg/pill), 2 pills each time, twice daily. Patients in the WM control group took Lovastatin Tablet (20 mg/tablet), 1 tablet each time, once daily. The course of treatment was 6 successive months for all. They avoided taking any lipid-regulating or anti-atherosclerotic drugs during the therapeutic course. The changes of Chinese medicine symptom scores, serum TC, TG, LDL-C, and HDL-C levels, IMT of the carotid artery, and the plaque integral before and after treatment were observed.</p><p><b>RESULTS</b>After 6 months of treatment the Chinese medicine symptom scores reduced in each group ( P<0.05 or P<0.01), and the treatment group was superior to WM control group (P<0.05). Serum TC, TG and LDL-C levels were significantly lowered (P<0.05 or P<0.01), showing no significant difference in inter-group comparison (P>0.05). There was no statistical significance of the serum HDL-C level in each group (P>0.05). The IMT and the plaque integral significantly reduced (P<0.05, P<0.01), showing no statistical difference among all groups. One patient in the WM control group dropped out because of transaminase elevation. No serious adverse reaction correlated with the drugs occurred during the therapeutic course in the rest two groups.</p><p><b>CONCLUSIONS</b>LRRMP showed definite effects on lipid-regulating and anti atherosclerosis. Its effects were equivalent to Xuezhikang Capsule and Lovastatin Tablet. Besides, it was safe and economic, and deserved further studies.</p>

Construction of a PCR chip for detecting genes associated with metastatic colorectal cancer and its preliminary application / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a PCR chip with a gene panel for predicting and diagnosing metastatic colorectal cancer.</p><p><b>METHODS</b>The PCR chip was constructed by integrating 29 genes related to colorectal cancer metastasis identified by gene chip analysis and 3 housekeeping genes into a gene panel. The PCR chip was used for detecting the mRNA expressions of the integrated genes in colorectal cell lines, cancerous specimen and adjacent normal mucosa. The primers for amplification were refined and optimized by several rounds of preliminary reactions.</p><p><b>RESULTS</b>The PCR chip containing the 29 candidate genes and 3 housekeeping genes was successfully constructed, which showed specific amplifications of the genes. The results of the PCR chip for detecting the mRNA of the 29 genes related to colorectal cancer metastasis showed a concordance rate of 86% (25 out of 29) with the gene chip data. Application of the PCR chip in the examination of the clinical specimens identified 15 differentially expressed genes between metastatic colorectal cancer and colorectal cancer without metastasis.</p><p><b>CONCLUSION</b>The constructed PCR chip is reliable in the prediction of metastasis of colorectal cancer, and provides a molecular means for evaluating the prognosis of colorectal cancer metastasis.</p>

Clinical significance of tissue factor and vascular endothelial growth factor expressions on CD14+ monocytes in patients with non Hodgkin lymphoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the values of tissue factor (TF) and vascular endothelial growth factor (VEGF) expressions on peripheral CD14+ monocytes in disease assessment, prognosis, and short-term efficacy evaluation of non-Hodgkin lymphoma (NHL) patients.</p><p><b>METHODS</b>TF and VEGF expressions on CD14+monocytes in 47 NHL patients (disease group) before chemotherapy and after 4 chemotherapy cycles and in 30 healthy subjects (control group) were detected by flow cytometry, and the potential relationship among TF, VEGF, International Prognostic Index (IPI), and short-term efficacy were analyzed.</p><p><b>RESULTS</b>TF and VEGF expressions on CD14 + monocytes in disease group were significantly higher than those in control group ( all P <0. 01) and positive correlation was showed between them (r = 0. 708, P = 0.00). TF and VEGF expressions in Ann Arbor stage III and IV (n = 22 and 19) , symptomatic (n = 22) , lactate dehydrogenase (LDH) increased (n = 21) , Eastern Cooperative Oncology Group (ECOG) score 2-4 (n = 12) and extranodal lesions >1 (n = 16) groups were significantly higher than those in Ann Arbor stage II (an = 6) , asymptomatic (an =25) , LDH normal (n = 26) , ECOG score 0-1 ( n = 35) and extranodal lesions ~1 ( na = 31) groups, respectively (all P <0.05). The expressions of TF and VEGF on CD14 + monocytes in high-risk (n = 7) or high-middle-risk (n = 11) groups were significantly increased compared with low-risk (n = 15) or low-middle-risk(n = 14) groups, respectively (all P <0. 01). TF and VEGF expressions in non-remission group before chemotherapy (n = 11) were both obviously higher than those in remission group (an = 36, all P <0. 01) , and after chemotherapy their expressions in remission group were significantly lower than those before chemotherapy (all P <0. 01) , while such significant changes were not observed in the non-remission group ( all P > 0. 05).</p><p><b>CONCLUSION</b>The high expressions of TF and VEGF on peripheral CD14 + monocytes can be useful markers in dis-ease assessment, prognosis evaluation and short-term efficacy observation of NHL patients.</p>

Diagnostic role of soluble triggering receptor expressed on myeloid cell-1 in patients with sepsis / 世界急诊医学杂志（英文）

BACKGROUND: Biomarkers may be helpful in risk stratification and prediction of mortality in septic patients. This study aimed to investigate the diagnostic role of soluble triggering receptor expressed on myeloid cell-1(sTREM-1), procalcitonin (PCT), C-reactive protein (CRP) and other inflammatory markers in patients with sepsis. METHODS: A total of 56 patients with systemic inflammation response syndrome (SIRS) who had been admitted to the ICU department of the Second Hospital of Tianjin Medical University between May 2009 and July 2010 were enrolled. They were divided into a sepsis group (n=32) and a SIRS group (n=24). Twenty-five non-SIRS patients served as controls. The sepsis group was sub-divided into a survival group and a death group according to 28-day prognosis. The values of sTREM-1, PCT, CRP, white blood cell (WBC), and neutrophil count percentage (N) were measured. Acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) score were determined within 24 hours. The correlation between sTREM-1 and APACHE Ⅱ score was analyzed. Quantitative data were analyzed by the F test or the Kruskal-Wallis test. RESULTS: The plasma level of sTREM-1 in the sepsis group was significantly higher than that in the SIRS group and control group. The plasma level of sTREM-1 in the non-survival group was significantly higher than that in the survival group. In the sepsis group, the plasma sTREM-1 level was positively correlated with APACHE Ⅱ score (rs=0.426, P= 0.032). The area under the ROC curve of sTREM-1 was 0.935, larger than that of PCT and CRP. CONCLUSION: Plasma sTREM-1 is useful in the diagnosis of sepsis at early stage. The increased level of sTREM-1 during the first 24 hours may be correlated with poor outcome of patients with sepsis.

Influence of dipyridamole on expression of PAC-1 and CD62p in patients with malignant lymphoma / 中国实验血液学杂志

This study was purposed to explore the expressions of platelet-activated markers PAC-1 and CD62p in peripheral blood of malignant lymphoma patients and the influence of dipyridamole on their expression. 32 lymphoma patients were divided into simple chemotherapy group (simple group) and chemotherapy plus dipyridamole group (combined group) randomly, and 15 healthy peoples were selected as control group. The dipyridamole of 100 mg/day was given to the patients in combined group. The expression levels of PAC-1, CD62p and fibrinogen (Fib) were detected by flow cytometry and magnetic bead method on day 0, 3, 7 and 14 of chemotherapy respectively. The results showed that the levels of PAC-1, CD62p and Fib in lymphoma patients were significantly higher than those in control group (p < 0.01, 0.05), moreover there was positive correlation between levels of PAC-1 and Fib (r = 0.549, p < 0.01). PAC-1 expression on day 0 and 3 of chemotherapy in simple group was higher than that on day 14 (p < 0.05, 0.01) and CD62p expression on day 3 of chemotherapy was higher than that on day 0, 7 and 14 (p < 0.05, 0.01). PAC-1 expression in combined group on day 14 of chemotherapy was lower than than on day 0 and 3 (p < 0.05, 0.01), and CD62p on day 14 was lower than that on day 3 of chemotherapy (p < 0.05); PAC-1 and CD62p expressions in combined group on day 3, 7 and 14 of chemotherapy were decreased than those in simple group, but Fib level was not changed significantly. It is concluded that the patients with malignant lymphoma usually accompany with platelet activation and hyperfibrinogenemia in peripheral blood. Applying dipyridamole routine dosage in chemotherapy can efficiently restrain platelet activation.

Expression and significance of Survivin and Smac in ovarian mucinous tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expressions and significances of Survivin and Smac in ovarian mucinous tumors.</p><p><b>METHODS</b>A total of 55 paraffin-embedded specimens of primary ovarian mucinous tumors were collected. SABC was used to detect protein expression of Survivin and Smac genes. Immunoelectron microscopy using colloidal gold labeling was performed to determine the subcellular localization and patterns of Smac protein expression.</p><p><b>RESULTS</b>(1) The cytoplasmic expression rates of survivin in benign, borderline and malignant ovarian mucinous tumors were 2/20, 12/15 and 20/20 respectively, which presents an improving trend.There were significant differences of survivin expression between benign vs. borderline lesions (P < 0.01), and benign vs. malignant tumors (P < 0.01). The nuclear expression rates of survivin in benign, borderline and malignant ovarian mucinous tumors were 1/20, 6/15 and 5/20, respectively, which presents a.declining trend.There was significant difference of survivin expression between benign vs. borderline tumors (P < 0.05). The positive expression rates of Smac among the three groups were 19/20, 9/15 and 3/20, respectively. There was significant difference among the three groups (P < 0.01 or < 0.05). There was a negative correlation between Survivin and Smac (r = -0.153, P < 0.01). (2) Colloidal gold labeling study demonstrated that mitochondrion intramembranous storage of Smac granules in the three groups were 24.1 ± 7.2, 11.1 ± 1.9 and 5.2 ± 1.7, respectively, and there were significant differences among the three groups (P < 0.01 or < 0.05). The extramemebranous Smac granules were 4.7 ± 3.0, 2.9 ± 1.0 and 1.7 ± 1.3, although without significant difference among the three groups (P > 0.05).</p><p><b>CONCLUSIONS</b>With the malignant development of ovarian mucinous tumors, the expressions of Survivin are up-regulated, and the expressions of Smac are down-regulated. Smac proteins exist mainly in an inactive intramembranous storage form inside of mitochondria.</p>