Effect of obesity induced by high-fat diet and adipose exosomes on knee post-traumatic osteoarthritis caused by destabilization of medial meniscus surgery in young mice / 药学学报

Obesity is an important risk factor related to osteoarthritis, but it′s role in post-traumatic osteoarthritis on young people need to further study. The internal mechanism except the mechanical loading may be associated with adipose exosomes. To examine the effect of obesity induced by high fat diet and adipose exosomes on knee post-traumatic osteoarthritis caused by destabilization of medial meniscus (DMM) surgery in young mice, 20 6-week-old C57BL/6J mice were randomly assigned to the control diet group (CD, n = 5), the DMM group (n = 5), the high fat diet group (HFD, n = 5) and the HFD plus DMM group (HFD+DMM, n = 5). The CD and DMM group were fed with a control diet, and the HFD and HFD+DMM group were fed with a high fat diet. We did the DMM surgery and the sham surgery on the mice when it was 10 weeks old. Extract obese and normal adipose exosomes, identify exosomes in vitro, and proceed fluorescence imaging in vivo using DiR staining. DMM+HFD-Exo group and DMM+CD-Exo group were injected the exosomes from the tail vain once a week (100 μL per shot with a concentration of 1 μg·μL-1). Second, 15 6-week-old C57BL/6J mice were randomly assigned to the DMM group (n = 5), the DMM plus obese adipose exosomes group (DMM+HFD-Exo, n = 5), and the DMM plus control diet adipose exosomes group (DMM+CD-Exo, n = 5). Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Nanjing University (IACUC-D2204005). All mice were sacrificed at the age of 18 weeks, the knee joints of the mice were harvested and fixed. We used micro CT to examine the samples and measured the bone volume/tissue volume, trabecular thickness, trabecular number and trabecular separation. Then the samples were decalcified and embedded in paraffin, and 4 μm thickness sections were stained with H&E and safranin O/fast green to observe the histological changes of the knee joint. The results showed compared with the control diet group, high fat diet induced obesity can aggravate the pathological changes of the post-traumatic osteoarthritis caused by DMM surgery, which shows in having a higher Mankin score. The surface of knee articular cartilage in the HFD+DMM group was rough, and the subchondral bone has an increase in bone sclerosis. Compared with the DMM group, obese adipose exosomes can exacerbate the pathological changes of the knee articular cartilage, while not influencing the subchondral bone. In conclusion, high fat diet induced obesity can aggravate the post-traumatic osteoarthritis caused by DMM surgery in young mice. The obese adipose exosomes mainly affect the surface of the knee articular cartilage.

Mismatched donor cell infusion-related syndrome following microtransplant in patients with acute myeloid leukemia / 中华医学杂志(英文版)

BACKGROUND@#Immunotherapies such as adoptive immune cell infusion and immune-modulating agents are widely used for cancer treatment, and the concomitant symptoms, including cytokine release syndrome (CRS) or immune-related adverse events (irAEs), are frequently reported. However, clinical manifestations induced by mismatched donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell (GPBMC) infusion in patients receiving microtransplant (MST) have not yet been well depicted.@*METHODS@#We analyzed 88 cycles of mismatched GPBMC infusion in patients with acute myeloid leukemia receiving MST and 54 cycles of chemotherapy without GPBMC infusion as a comparison. Clinical symptoms and their correlation with clinical features, laboratory findings, and clinical response were explored.@*RESULTS@#Fever (58.0% [51/88]) and chills (43.2% [38/88]) were the significant early-onset symptoms after GPBMC infusion. Patients possessing less human leukocyte antigen-matching loci with the donor or those with unrelated donors experienced more chills (3 [2-5] loci vs. 5 [3-5] loci, P  = 0.043 and 66.7% [12/18] vs. 37.1% [26/70], P  = 0.024). On the other hand, those with decreased CD4 + /CD8 + T-cell ratio developed more fever (0.8 [0.7-1.2] vs. 1.4 [1.1-2.2], P  = 0.007). Multivariable analysis demonstrated that younger patients experienced more fever (odds ratio [OR] = 0.963, 95% confidence interval [CI]: 0.932-0.995, P  = 0.022), while patients with younger donors experienced more chills (OR = 0.915, 95% CI: 0.859-0.975, P  = 0.006). Elevated ultra-sensitive C-reactive protein levels in the absence of cytokine storm were observed following GPBMC infusion, which indicated mild and transient inflammatory response. Although no predictive value of infusion-related syndrome to leukemia burden change was found, the proportion of host pre-treatment activated T cells was positively correlated with leukemia control.@*CONCLUSIONS@#Mismatched GPBMC infusion in MST induced unique infusion-related symptoms and laboratory changes, which were associated with donor- or recipient-derived risk factors, with less safety and tolerance concerns than reported CRS or irAEs.

Exploration and practice of building tele-critical care system / 中华危重病急救医学

Objective:To look for the problems faced in the construction of the tele-critical care system, explore the framework of construction of the tele-critical care system, and verify the application effects of the established tele-critical care system.Methods:Through literature review and on-site investigation and demonstration, the causes affecting the construction of the tele-critical care system were explored. Through on-site investigation of the actual situation of the critical care department in relevant hospitals, arguing and choosing intended intensive care unit (ICU) and cooperative third-party communication and equipment companies, and through the Internet of Things and 5G communication technology, a tele-critical care system with the core hospital of the group as the center and the member institutes within the group as the nodes was built. Via the established tele-critical care system, activities such as tele-monitoring, visual remote ward rounds, remote consultation, remote teaching were carried out to verify the functions of the system.Results:The insufficient cognition of relevant personnel, tele-medicine practice certification requirements, information security issues and the barriers of equipment information integration were the main causes affecting the construction of tele-critical care system. There were five parts in the tele-critical care system architecture foundations, including bed unit equipment and audio and video information collection system, lossless and secure transmission of collected information, real-time display of information in the remote center, real-time staff interaction between the centre and the nodal hospitals, and information cloud storage. It has been verified that patients' diagnostic and treatment information can be transmitted safely, losslessly and in real-time by a special line through private 5G network. Through this system, real-time and stable upload of audio and video information of patients and application information of monitors, ventilators and infusion work stations can be achieved; combined with tele-conference connections to conduct two-way communication with local medical staff, real-time tele-monitoring, visual remote ward rounds, remote consultation, remote teaching and other functions can be achieved.Conclusion:The tele-critical care system we established is feasible to construct within the medical group and can safely and effectively realize the functions of real-time tele-monitoring, visual remote ward rounds, remote consultation, and remote teaching.

Molecular Mechanism of Aurora Kinase A Regulating the Meiosis of Oocyte / 中国医学科学院学报

Aurora kinase A (AURKA),a family member of aurora kinases,is involved in mitotic entry,maturation and separation of centrosome,assembly and stabilization of bipolar spindle,and condensation and separation of chromosome.Studies have demonstrated that AURKA plays a similar role in meiosis,while the specific mechanism and the similarities and differences in its role between meiosis and mitosis remain unclear.Therefore,we reviewed the studies about the localization and activation of AURKA in oocyte meiosis,and compared the role of AURKA in regulating spindle formation,activating spindle assembly checkpoint,and correcting the kinetochore-microtubule attachment between the meiosis of oocytes and the mitosis of somatic cells.This review will lay a theoretical foundation for revealing the mechanism of AURKA in the regulation of cell division and for the clinical research related to cancer and reproduction.

Comparison of sequential feeding and continuous feeding on the blood glucose of critically ill patients: a non-inferiority randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Glucose control is an important aspect in managing critically ill patients. The goal of this study was to compare the effects of sequential feeding (SF) and continuous feeding (CF) on the blood glucose of critically ill patients.@*METHODS@#A non-inferiority randomized controlled trial was adopted in this study. A total of 62 patients who were fed enteral nutritional suspension through gastric tubes were enrolled. After achieving 80% of the nutrition target calories (25 kcal·kg-1·day-1) through CF, the patients were then randomly assigned into SF and CF groups. In the SF group, the feeding/fasting time was reasonably determined according to the circadian rhythm of the human body as laid out in traditional Chinese medicine theory. The total daily dosage of the enteral nutritional suspension was equally distributed among three time periods of 7 to 9 o'clock, 11 to 13 o'clock, and 17 to 19 o'clock. The enteral nutritional suspension in each time period was pumped at a uniform rate within 2 h by an enteral feeding pump. In the CF group, patients received CF at a constant velocity by an enteral feeding pump throughout the study. Blood glucose values at five points (6:00/11:00/15:00/21:00/1:00) were monitored and recorded for seven consecutive days after randomization. Enteral feeding intolerance was also recorded. Non-inferiority testing was adopted in this study, the chi-square test or Fisher test was used for qualitative data, and the Mann-Whitney U test was used for quantitative data to determine differences between groups. In particular, a repeated measure one-way analysis of variance was used to identify whether changes in glucose value variables across the time points were different between the two groups.@*RESULTS@#There were no significant demographic or physiological differences between the SF and CF groups (P > 0.050). The average glucose level in SF was not higher than that in CF (8.8 [7.3-10.3] vs. 10.7 [9.1-12.1] mmol/L, Z = -2.079, P for non-inferiority = 0.019). Hyperglycemia incidence of each patient was more common in the CF group than that in the SF group (38.4 [19.1-63.7]% vs. 11.8 [3.0-36.7]%, Z = -2.213, P = 0.027). Hypoglycemia was not found in either group. Moreover, there was no significant difference during the 7 days in the incidence of feeding intolerance (P > 0.050).@*CONCLUSIONS@#In this non-inferiority study, the average blood glucose in SF was not inferior to that in CF. The feeding intolerance in SF was similar to that in CF. SF may be as safe as CF for critically ill patients.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT03439618; https://clinicaltrials.gov/ct2/show/record/NCT03439618.

Retrospective study on the merits of bone grafts and the influence of implant protrusion length after osteotome sinus elevation surgery / 华西口腔医学杂志

OBJECTIVES@#This study aims to evaluate the endo-sinus bone remodeling of dental implants placed via osteotome sinus floor elevation (OSFE) after 6 months and using different implant protrusion lengths and bone grafts through cone beam computed tomography (CBCT).@*METHODS@#Ninety-six patients with 124 implants were included and assigned into four groups. Group 1: implant protrusion length4 mm with bone graft; group 3: implant protrusion length4 mm without bone graft. Apical bone gain (ABG), cortical bone gain (CBG), bone density gain (BDG), and marginal bone loss (MBL) were observed and analyzed at baseline and 6 months after implant surgery.@*RESULTS@#The CBG in grafted groups 1 and 2 was higher than that in non-grafted groups. The ABG and BDG were higher in non-grafted groups 3 and 4 than in grafted groups, and the levels in group 3 were higher than those in group 4. The CBG in grafted group 2 was higher than that in group 1. No significant difference was observed in MBL analysis.@*CONCLUSIONS@#The BDG of IPL4 mm implant when bone grafts were not applied. No relevance was observed between IPL and CBG. Bone grafts can accelerate endo-sinus bone remodeling by increasing CBG and dissipating the influence of IPL on BDG.

Systems Pharmacology Ⅲ: Application Progress in Interpretation of Holistic Mechanism of Traditional Chinese Medicine / 中国实验方剂学杂志

Holistic medicine is an interdisciplinary field that integrates all types of biological information (proteins, small molecules, tissues, organs, external environmental signals, etc.) to provide predictable and operational models for healthcare and disease treatment. Despite the global and integrative character of this discipline, scientific evidences to clarify the mechanism of holistic medicine is still lacking. Systems pharmacology, as a newly developed discipline based on the interdisciplinary and integration of classical pharmacology, computer technology, bioinformatics, and network pharmacology, has systematically studied the interaction between drugs and the human body, as well as its law and nature at the molecular, cellular, organ and network levels. Since its birth in 2011, this discipline has been widely used in the research of the promotion of holistic medicine, compound analysis, the development of new drugs, and interpretation of basic theories of traditional Chinese medicine (TCM). In this paper, in order to provide new methods and ideas for the modernization of holistic medicine, the authors introduce the research ideas of systems pharmacology of TCM in detail, and the mechanism of holistic medicine in the treatment of complex diseases is explained by sorting out the researches of systems pharmacology on multi-component, multi-target, multi-pathway, multi-function, compatibility of TCM, etc.

Clinical significance of bilateral lung asymmetry signs of bedside ultrasound in severe patients / 中华危重病急救医学

Objective:To study the clinical significance of bilateral asymmetric signs of lungs of bedside ultrasound in order to improve the diagnosis and treatment of pulmonary diseases and protocol of pulmonary ultrasound.Methods:The ultrasound imaging data of patients admitted to the department of critical care medicine of the Affiliated Hospital of Qingdao University from September 2017 to May 2019 were retrospectively analyzed. The clinical data of patients were collected, and the lung ultrasound image data and clinical diagnosis were sorted and analyzed.Results:A total of 535 critical patients ultrasound imaging data were reviewed, and 469 patients who were unable to obtain clear lung ultrasound images and lung symmetry signs were excluded. Finally, a total of 66 patients with ultrasound bilateral lung asymmetry signs during hospitalization were enrolled in the analysis. Seventeen patients (25.76%) had pneumothorax with unilateral pleural slide or lung spot, 12 (18.18%) had pneumonia with unilateral focal B line, fragment sign and tissue like sign, 21 (31.82%) had unilateral pleural effusion with unilateral liquid dark area, 8 (12.12%) had sputum obstruction with unilateral local lung consolidation and bronchial filling sign with atelectasis, and 5 (7.58%) had deep tracheal intubation. The above ultrasonic diagnoses were confirmed by chest X-ray, chest CT, fiberoptic bronchoscopy and laboratory examination. One patient with unilateral focal B-line was transferred to another hospital for treatment, and 2 patients died of sudden death due to disappearance of unilateral pleural sliding sign or unilateral pulmonary pulsation sign. The clinical diagnosis was not clear (4.54%).Conclusion:The asymmetric signs of pulmonary ultrasound clearly indicate the existence of pulmonary diseases that need to be treated in a timely manner, and the pulmonary ultrasound examination protocol of bilateral contrast is helpful for clinical diagnosis.

Research of Feiliuping Gao and its combination with different types of drugs intervention on expression of PI3K/AKT/NF-κB in lung metastatic microenvironment / 中国中药杂志

The aim of this paper was to observe the effect of Feiliuping Gao and its combination with different types of drugs intervention on the expression of PI3K/AKT/NF-κB in lung metastatic microenvironment, and to reveal the advantage of Chinese medicine intervention time on the key molecule in lung metastatic microenvironment. The mouse model of Lewis lung carcinoma was established, and lung tissues were collected at 14 days, 21 days and 28 days after the intervention of Feiliuping Gao, and the expressions of PI3K, AKT and NF-κB were detected by immunohistochemistry and Western blot. At 14 days, there was no significant difference in PI3K expression between each group and the control group. The expression of AKT protein was significantly inhibited in the celecoxib (CLB) group, the Feiliuping Gao (FLP) combination with cyclophosphamide (FLP+CTX) group, and the Feiliuping Gao combination with celecoxib (FLP+CLB) group (<0.05). The inhibition of AKT protein expression in FLP+CLB group was superior. The FLP+CLB group can inhibit the expression of NF-κB protein (<0.05). At 21 days, compared with the control group, the expression of PI3K was inhibited in FLP group and the FLP+CTX group (<0.05), while the expression of PI3K was best inhibited in the FLP+CLB group (<0.001). Only the FLP+CLB group could significantly inhibit the expression of AKT protein (<0.01). The FLP+CTX group had the best effect in inhibiting the expression of NF-κB protein (<0.001). At 28 days, compared with the control group, the expression of PI3K and AKT was inhibited in the FLP+CLB group (<0.001). Feiliuping ointment combination with celecoxib has an advantage in regulating the expression of PI3K/AKT/NF-κB molecules in lung metastatic microenvironment.

Using peripheral perfusion index and venous-to-arterial CO2difference/arterial-central venous O2 difference ratio to assess lactate clearance in septic patients after resuscitation / 中华内科杂志

Objective The relationship of venous-to-arterial CO2difference(Pv-aCO2)/ arterial-central venous O2difference (Ca-vO2) ratio, peripheral perfusion index(PI) and lactate clearance(LC) were investigated during resuscitation in septic patients. And, the meaning of the combination PI and Pv-aCO2/Ca-vO2ratio to interpret incoherence of lactate clear was explored. Methods The patients with sepsis were prospectively observed, who admitted to critically care medicine department of Peking Union Medical College Hospital. The hemodynamic parameters, simultaneous arterial and central venous blood gas analysis and PI were obtained at the enrollment (T0) and 8 hours (T8) during resuscitation. The lactate clearance was defined as 8h-LC≥10% and non-lactate clearance was defined as 8h-LC≤10%. Additionally, the patients were divided as three sub-groups according to the PI value at T8: the normalized PI group with PI≥1.4,the mild impaired PI with 1.4＜PI＜0.6 and severe impaired PI with PI≤0.6. Results A total of 84 patients were enrolled in this study. There was no significant difference in Pv-aCO2/Ca-vO2ratio in the three groups. However, the PI≤0.6 group had a significantly higher Pv-aCO2than other groups. Moreover, the patients with non-lactate clearance (13/32) had a higher Pv-aCO2/Ca-vO2ratio than the patients with lactate clearance in PI≥1.4 group (1.9±0.7 vs. 1.3±1.0, P=0.01). Multivariate analysis showed both Pv-aCO2/Ca-vO2ratio [Exp(B) 2.235,95% CI 1.232-4.055,P=0.008] and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) [Exp(B)1.087,95%CI 1.022-1.156,P=0.008] were independent risk factor of non-lactate clearance. 8h-PI was significantly negative correlated with the 8 h Pv-aCO2gap (r=-0.311, P=0.004), but not significantly with Pv-aCO2/Ca-vO2ratio (r=-0.094, P=0.385). Conclusions Both high Pv-aCO2/Ca-vO2 ratio and low PI were related to non-lactate clearance after resuscitation in sepsis. Combined PI and Pv-aCO2/Ca-vO2ratio could interpret incoherence of latacte clearance after resuscitation.

Impacts of bladder and rectum filling status on their dosimetric parameters in helical tomotherapy for cervical cancer / 中华放射肿瘤学杂志

Objective To analyze the changes in volume and the planning volume of the bladder and rectum during helical tomotherapy (HT) treatment for cervical cancer,and to evaluate the impacts of bladder and rectum filling on their dosimetric parameters.Methods Twenty patients with cervical cancer who received HT in our hospital from 2012 to 2016 were enrolled as subjects.Before treatment,megavolt computed tomography (MVCT) and registration of planning CT images were preformed to recalculate the dose distribution,delineate the target volume,and measure the volume and position of the bladder and the rectum.Each MVCT image and the corresponding single dose were obtained by dose reconstruction using the Planned Adaptive module in HT planning workstation.The fused MVCT images and the corresponding single dose for each MVCT were loaded to MIM Maestro software 6.0 for dose stacking.The obtained total radiation dose was compared with that obtained by kilovolt CT.Between-group comparison was made by paired t-test or analysis of variance.Results If the volume change in the bladder was more than 400 ml or the rate of volume change was higher than 60％,the displacements of the bladder centroid toward the foot and dorsal sides were significantly increased;the Dmean and V50 were significantly increased (P＜0.05).If the volume change in the rectum was more than 30 ml or the rate of volume change was higher than 30％,the displacements of the rectum centroid toward the head and ventral sides were significantly increased;the V45 and V50 for the rectum were significantly increased (P＜0.05).Conclusions Although the bladder filling status has little effect on the radiation dose to the bladder,the volume change or the rate of volume change should be no more than 400 ml or 60％,respectively.Moderately filled bladder is recommended for positioning and treatment,which achieves satisfactory repeatability of the treatment.A volume change of more than 30 ml or a rate of volume change of higher than 30％ can result in an increase in the dose to the rectum.Empty rectum can effectively reduce the dose to the rectum.

Significance of Monitoring Minimal Residual Disease by Flow Cytometry in Acute Leukemia Patients Underwent Nonmyeloablative Allo-HSCT / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the value of dynamically monitoring minimal residual disease (MRD) by flow cytometry before and after non-myeloablative allo-HSCT (NST) for prediction of acute leukemia(AL) relapse after transplantation.</p><p><b>METHODS</b>The clinical data of 51 AL patients underwent NST were analyzed retrospectively in Department of Hematology of Affiliated Hospital of Academy of Military Medical Sciences from January 2011 to December 2015. All AL patients achieved the morphologic complete remission of bone marrow before transplantation. The bone marrow samples were collected for monitoring of MRD within 35 days before transplant, every month till 3 months after transplant, every 3 months till 24 months after transplant, and then every 6 months after 2 years of transplant. According to the MRD cutoff value of 0.2%, the AL patients were divided into high level MRD group (18 cases) which was defined as MRD≥0.2% after transplantantion at least for 1 time, and low level MRD group (33 cases) which was defined as MRD<0.2% after transplant all the time. 2 year cumulative relapse rate in 2 groups were compared.</p><p><b>RESULTS</b>Two-year relapse rates were 6.1% and 50% in low-level MRD group and high-level MRD group post NST(P=0.001)respectively. Multivariate analysis indicated that the risk of relapse in high level MRD group was 5.84 times of low level MRD group(P=0.036). MRD≥0.2% post transplant was an independent risk factor for leukemia relapse post NST. The mortality rate was 81.8% and 46.3%(P<0.05) in relapse and non-relapse groups respectively.</p><p><b>CONCLUSION</b>Dynamically monitoring MRD by FCM is a crucial tool for early relapse estimation of acute leukemia in adult patients after allogeneic nonmyeloablative hematopoietic stem cell transplantation. MRD≥0.2% after transplant can be used as a early valuable evidence for predicting relapse and guiding active medical intervention.</p>

Autophagy and its role in the pathogenesis of multiple sclerosis / 解放军医学杂志

Autophagy generally reside in eukaryote and is a highly conserved protein degradation pathway,which take part in the maintenance of cellular homeostasis as well as the growth of cells.The characterization of autophagy being reported over years has revealed that it involved in immune response,such as removal of intracellular bacteria,inflammatory cytokine secretion,antigen presentation,and lymphocyte development,and then involved in the pathogenesis of multiple sclerosis indirectly.So,in this review,we focus on the pathway ofautophagy and the role of which in the multiple sclerosis (MS) in order to further understand the important effect and potential therapeutic value of autophagy in MS.

Characterization of Avian Influenza A (H7N9) Virus Prevalence in Humans and Poultry in Huai'an, China: Molecular Epidemiology, Phylogenetic, and Dynamics Analyses / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To trace the source of human H7N9 cases in Huai'an and elucidate the genetic characterization of Huai'an strains associated with both humans and birds in live poultry market.</p><p><b>METHODS</b>An enhanced surveillance was implemented when the first human H7N9 case was confirmed in Huai'an. Clinical specimens, cloacal swabs, and fecal samples were collected and screened by real-time reverse transcription-polymerase chain reaction (RT-PCR) for H7N9 virus. The positive samples were subjected to further RT-PCR and genome sequencing. The phylodynamic patterns of H7N9 virus within and separated from Huai'an and evolutionary dynamics of the virus were analyzed.</p><p><b>RESULTS</b>Six patients with H7N9 infection were previously exposed to live poultry market and presented symptoms such as fever (>38.0 °C) and headaches. Results of this study support the hypothesis that live poultry markets were the source of human H7N9 exposure. Phylogenetic analysis revealed that all novel H7N9 viruses, including Huai'an strains, could be classified into two distinct clades, A and B. Additionally, the diversified H7N9 virus circulated in live poultry markets in Huai'an. Interestingly, the common ancestors of the Huai'an H7N9 virus existed in January 2012. The mean nucleotide substitution rates for each gene segment of the H7N9 virus were (3.09-7.26)×10-3 substitutions/site per year (95% HPD: 1.72×10-3 to 1.16×10-2).</p><p><b>CONCLUSION</b>Overall, the source of exposure of human H7N9 cases in Huai'an was live poultry market, and our study highlights the presence of divergent genetic lineage of H7N9 virus in both humans and poultry specimens in Huai'an.</p>

Features of Immunophenotypes and Characteristics of Molecular Biology and Cellular Genetics of AML Patients with CD4 and CD7 Expression / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the features of immunophenotypes and the characteristics of molecular biology and cellular genetics of AML patients with CD7 and CD4 expression.</p><p><b>METHODS</b>The immunophenotypical markers of AML cells were detected by multiple parameter flow cytometry; the expression of WT1, MDK, ETO, PML-RaRa and BCR-ABL were detected by RT-PCR; and cellular features were analyzed by R-band in 304 patients. The patients were divided into three groups according to their immunophenotypes: AML with CD7 expression (CD7 group), AML with CD4 expression(CD4 group) and AML without CD7 and CD4 expression (common AML group).</p><p><b>RESULTS</b>The expression rate and level of HLA-DR in CD7 group were higher than those in the common AML group, and the expression rate of CD33 and CD34 was higher than that in the other two groups. The expression rate and level of CD15, CD64 in the CD4 group were higher than those in the other 2 groups, and the expression rate and level of CD33 were higher than those in the common AML group. WT1 expression in the CD7 group was lower than that in the common AML group. PML-RaRa was not detected in the CD7 group. AML with co-expression of CD4 or CD7 showed more normal karyotype. (15;17) was not found in AML with CD7 expression.</p><p><b>CONCLUSION</b>AML cells with CD7 expression originate from precursor cells and are blocked in the early phase of hematological development; AML cells with CD4 expression originate from more mature stage of hematological devevelopment and with CD33, CD64 and CD15 high expression; AML cells with CD7 and CD4 expression are characterized by no-specific change of cellular genetics. According to the expression level and intesity of CD4 and CD7, and together with other specific lineage markers, the MRD in AML patients can be quantitatively detected.</p>

Characteristics and Prognosis of 24 Cases of Primary Acute Myeloid Leukemia with Trisomy 8 / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical features and prognosis of primary acute myeloid leukemia (AML) with trisomy 8.</p><p><b>METHODS</b>The clinical data of 24 cases diagnosed as primary AML with trisomy 8 were collected. The clinical characteristics such as sex, age, subtype of FAB, blood routine and bone marrow blast at the first visit were analyzed and the relationship of the characteristics with CR rate and the prognosis was explored.</p><p><b>RESULTS</b>12 out of 24 AML patients were diagnosed as M5 (50%), while M2, M3, M4 and M6 had 3 cases, respectively (12.5%); one case did not receive the chemotherapy. 23 cases received 1-2 cycles of standard induction chemotherapy. Among them 3 cases of M3 achieved complete response (CR) and survived until the last following up with 100% 5-year OS rate. Among 20 cases of non-M3, 12 cases achieved CR1 (60%), 4 cases achieved partial response (PR) (20%), 4 cases did not respond (NR); 5 cases relapsed in follow-up for 3 years after CR1 (41.7%), 3 cases achieved CR2 after re-induction chemotherapy, and 2 cases remained NR. Among 20 cases of non-M3, 1 case failed to be followed-up after diagnosis within 1 month. The mean follow-up time of 19 cases was 26.2 (1.5-84) months, 9 cases died (6 cases of M5, 1 case of M4 and 2 cases of M2), who achieved PR and NR, or relapsed after CR1; the 3-year DFS and OS were 21%, 31.5% respectively. 2 cases of non-M3 accepted allo-HSCT with HLA-matched sibling donor and kept disease-free survival until the last following up, and survived for 58 and 66 months respectively. Except for 3 cases of M3, 2 cases received allo-HSCT and the cases without chemotherapy, the other 18 cases with initial WBC count less than 10×10(9)/L had OS and DFS longer than those of 10 cases with initial WBC count no less than 10×10(9)/L (P<0.05, P<0.01). The OS of 10 cases with CR1 was longer than OS of those cases without CR1 (P<0.01).</p><p><b>CONCLUSION</b>The incidence of trisomy 8 in M5 is higher than the other AML subtypes, and the prognosis of M5 is poor. The initial WBC count above 10×10(9)/L is a high-risk factor. M3 with trisomy 8 and RARA gene has a very good prognosis. Trisomy 8 may increase the risk of primary AML except for M3, so allo-HSCT with HLA-matched sibling donor should be carried out as much as possible after CR1. The gene mutation of FLT3, MLL, HOX11, C-kit, NPM1 may possess an important significance on prognosis.</p>

Expression of 8-oxodG in Oral Leukoplakia / 沈阳医学院学报

Objective:To study the expression of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in oral leukoplakia for clarifying the role of oxidative DNA damage in the development of oral leukoplakia. Methods:Immunofluorescence labeling method was used to examine the expression of 8-oxodG,a marker of oxidative DNA damage,and the expression of tumor suppressor gene, P53 protein in oral epithelium of normal oral mucosa and biopsy specimens of leukoplakia. Results:In specimens of oral leukoplakia, HE staining showed infiltration of inflammatory cells, hyperkeratosis and epithelial dysplasia. Immunofluorescence labeling study demonstrated that the accumulation of 8-oxodG apparently increased in the oral epithelium of patients with leukoplakia,whereas little or no immunoreactivity was observed in normal oral mucosa. Expression of P53 protein was also observed in oral epithelium of patients with oral leukoplakia. The immunoreactivity of 8-oxodG and P53 was stronger in patients with oral leukoplakia than that in normal oral mucosa (P<0.01) . Moreover,the immunoreactivity increased with the development of disease (r=0.773, P<0.01) . Conclusions:The oxidative DNA damage contributes to the development of oral leukoplakia. 8-oxodG may be a risk predictive marker for oral leukoplakia.

Clinical efficacy of switching to 2nd generation of tyrosine kinase inhibitor on CML patients at poor responses to imatinib / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This study was to investigate the timing and clinical efficacy of switching to the 2nd generation of tyrosine kinase inhibitor (TKI) for CML patients at poor response to imatinib (dissatifed efficacy or intolerance).</p><p><b>METHODS</b>The therapeatic efficacy and side reaction of switched 2nd TKI in patients with newly diagnsed CML-CP who poorly responded to imatinib were observed, anong them 3 cases were intolerant, 6 cases did not acquire satisfied efficacy.</p><p><b>RESULTS</b>After switching to 2nd generation TKI, 3 patients with intolerance achieved complete cytogenetic remission (CCyR) in 3 months, and major molecular remission (MMR) in 3-6 months. All of them achieved optimal efficacy according to European Leukemia Network (ELN), but the pleural effusion appeared in 1 case after use of 2nd generation of TKI for 3 months, and the dadatinib was stoped temporally, and the curative efficacy still was maintained. Among 6 cases with poor efficacy by treatment with imatinib, 2 cases with BCR/ABL mutation progressed after switching 2nd generation of TKI, out of them 1 case with poor tolerance progeressed to the accelerated phase, but was cured by haploidentical allogeneic hematopoictic stem cell transplantation, 1 case progressed to blastic crisis and died of serious infection; the another 4 cases achieved MMR in 3-12 months after using 2nd generation of TKI, and maintained CMR for 12-36 months.</p><p><b>CONCLUSION</b>CML-CP patients without the optimal response to imatinib should be treated by switching to 2nd generation of TKI as soon as possible, and thereby patients may acquired satisfactory therapentic efficacy.</p>

Effect of suramin on trabeculectomy in rabbit / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the effect of suramin concentration changes on trabeculectomy in rabbit, and to provide treatment strategies for glaucoma on the basis of experiment. METHODS:Thirty-two albino rabbits were randomly divided into four groups, including standard control group, experimental group Ⅰ, experimental group II, and experimental group Ⅲ. Each eye was performed standard trabeculectomy. During surgery, standard control group was given a piece of cotton with 0. 3mg/mL mitomycin C ( MMC ) for 2min, and the other three groups were given a piece of cotton with 0. 3, 0. 4, and 0.5mg/mL suramin respectively for 2min. The filtering blebs and intraocular pressure ( IOP ) were observed at the 3, 7, 15, and 30d after surgery. Some conjunctiral specimen were observed with hitochemicall ( HE staining) and immunohistochemicall methods. RESULTS:At postoperative 7, 15, and 30d, the changes of the IOP, functional filtering blebs, and the number of positive cell nuclear in experimental group II and experimental group Ⅲ were significantly different compared with those in standard control group and experimental group Ⅰ (all P0. 05). The changes of the IOP and the number of positive cell nuclear in experimental group Ⅲ were significantly different compared with those in experimental group II (P0. 05). The status of filtering channel in experimental groupII and experimental group Ⅲ were better than those in experimental group Ⅰ and standard control group. CONCLUSION: The concentration of suramin has a significantly influence on its effect. When the concentration is 0. 3mg/mL, the antiproliferative effect of suramin is no more than that of MMC. The effect of 0. 4, 0.5mg/mL suramin is better than MMC. 0. 5mg/mL suramin has a better effect on controlling IOP and suppressing the growth of fibroblasts than 0. 4mg/mL suramin.

Variation of organ position and dose for cervical cancer patients treated with helical tomotherapy / 中华放射医学与防护杂志

Objective To observe the interfractional variation and actual dose for cervical cancer patients treated with tomotherapy.Methods Five patients who received tomotherapy were chosen from Aug 2013 to Feb 2014.A megavohage computed tomography (MVCT) scan was performed before treatment and then registered with the planning CT images.Dose distributions were recalculated and targets were contoured on the MVCT images.The differences between the actual radiation and planning were analyzed.Results In the patients received external radiotherapy, the decline in cervix volume and maximum diameter was 68.90％ and 26.91％ , respectively (t =5.21, 8.39, P ＜0.05).Cervix, uterus and CTV movement in left-right, anteroposterior, superoinferior were 1.43,-7.72, 0.02,-0.40,-1.24, -6.51,-0.43,-1.68and-0.22mm.The medianCTV V95％ was 99.40％ (95.96％-100％), and missing volume was 6.94 cm3 (0-32.30 cm3).Conclusions During radiotherapy for cervical cancer patients, the volume, position and doses are different between initial plan and actual radiation.Based on image guided radiation therapy (IGRT), missing targets are limited.