Diagnosis and treatment of 4 cases imported severe malaria and COVID-19 co-infection / 中国热带医学

@#Abstract: To explore the clinical characteristics, diagnosis and treatment of imported severe malaria and COVID-19 co-infection cases, and to provide scientific basis for epidemic prevention and control measures. The epidemiological characteristics, clinical manifestations, laboratory tests, treatment process and prognosis of 4 cases of severe malaria and COVID-19 co-infection with confirmed diagnosis were analyzed retrospectively. Four cases of severe malaria were African returnees of the same batch, male, aged 40-54 years old, with the same journey track. They all had African work and life history and acute onset. The main clinical manifestations were fever (4/4), chills (3/4), chills (3/4), nausea and vomiting (3/4), diarrhea (4/4), fatigue and anorexia (4/4). Two cases had headache and dizziness, confusion, muscle aches, two cases had cough, one cases had sputum, sore throat and runny urine. All 4 cases were confirmed by positive nucleic acid detection of the new coronavirus (2019-nCOV) in throat swabs. Plasmodium falciparum was found by microscopic examination of peripheral blood smears of all patients, and all of them were consistent with high altitude helminthiasis. All cases were accompanied by abnormal liver function and severe hypoproteinemia, two cases were hyperbilirubinemia, three cases were dyslipidemia, three cases were involved in abnormal tertiary hemogram with different degrees of elevation of procalcitonin, two cases were lactic acid poisoning, and one case was hypoglycemia. One case showed viral pneumonia on chest CT. All cases were treated individually according to the different conditions and were discharged after improvement, and were rechecked for 2019-nCOV nucleic acid and microscopic examination of blood smear negative for Plasmodium.During the global COVID-19 epidemic, the emergence of coinfection cases of con-infection of imported malaria parasites and severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2) makes the clinical diagnosis and treatment more complicated. It is important to establish the awareness of simultaneous prevention and diagnosis of COVID-19 and malaria for local prevention and control and early warning of severe cases, and timely and effective formulation of treatment plan to improve the comprehensive treatment efficiency.

Effect of Huazhuo Jiedu Shugan Prescription on Learning， Memory， and PI3K/Akt/GSK-3β Signaling Pathway in Epileptic Rats / 中国实验方剂学杂志

Objective:To observe the effects of Huazhuo Jiedu Shugan Prescription （HZJDSG） on learning， memory， and the expression of phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/glycogen synthase kinase-3<italic>β</italic> （GSK-3<italic>β</italic>） pathway-related proteins in epileptic rats， and to explore its possible mechanism. Method:Forty-eight SPF male SD rats were randomly divided into a normal group， a model group， a sodium valproate （0.19 g·kg^-1） group， and low- （2.7 g·kg^-1）， medium- （5.4 g·kg^-1）， and high-dose （10.8 g·kg^-1） HZJDSG groups， with eight rats in each group. The normal group received 0.9% sodium chloride solution （0.035 g·kg^-1） by intraperitoneal injection， and the other five groups received pentetrazol （PTZ） at the same dose to induce a chronic epilepsy model for a total of 14 times. The drug groups received corresponding drugs and the normal group and the model group received 0.9% sodium chloride solution at the same volume once a day for 28 days. During the drug intervention period， epilepsy was maintained in each modeling group by intraperitoneal injection of PTZ on day 7， 14， 21， and 28. The behavioral changes of rats were observed by Morris water maze and the pathomorphological changes of rat hippocampal neurons by hematoxylin-eosin （HE） staining. The protein expression of phosphorylation Akt（p-Akt）and p-GSK-3<italic>β</italic> was detected by immunohistochemistry and the protein expression of PI3K， Akt， p-Akt， GSK-3<italic>β</italic>， and p-GSK-3<italic>β</italic> by Western blot. Result:Compared with the normal group， the model group showed prolonged platform finding time （<italic>P</italic><0.01）， reduced number of platform crossings （<italic>P</italic><0.01）， structural damage of neurons in the CA1 region of the hippocampus， down-regulated protein expression of p-Akt and p-GSK-3<italic>β </italic>in the CA1 region of the hippocampus （<italic>P</italic><0.05）， and reduced relative expression of PI3K， p-Akt， and p-GSK-3<italic>β</italic> in the hippocampus （<italic>P</italic><0.01）. Compared with the model group， the sodium valproate group and the HZJDSG groups showed shortened platform finding time （<italic>P</italic><0.01） and improved neuronal structure in the CA1 region of the hippocampus， while the sodium valproate group and the high- and medium-dose HZJDSG groups exhibited increased number of platform crossings （<italic>P</italic><0.01）， up-regulated protein expression of p-Akt and p-GSK-3<italic>β</italic> in the CA1 region of the hippocampus （<italic>P</italic><0.05）， and elevated relative expression of PI3K， p-Akt， and p-GSK-3<italic>β</italic> （<italic>P</italic><0.01）. Conclusion:HZJDSG can improve the learning and memory of epileptic rats， and its antiepileptic effect may be achieved by the activation of PI3K/Akt/GSK-3<italic>β</italic> pathway-related proteins.

Analysis of RUNX1 Gene Mutation in Patients with Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the mutation of RUNX1 gene in patients with myelodysplastic syndrome (MDS) and its correlation with other gene mutations and some clinical parameters.@*METHODS@#The mutations of RUNX1, DNMT3A, TET2, IDH1/2, NPM1, FLT3-ITD and C-KIT in 170 patients with MDS were detected by direct and indirect sequencing of genomic DNA-PCR amplification products.@*RESULTS@#The RUNX1 mutation was found in 23 patients (13.5 %, 23/170). Among the 170 patients, other most frequent mutation was TET2 (11.2%, 19/170), followed by mutations in DNMT3A (9.4%, 16/170), NPM1 (8.2%, 14/170), IDH2 (4.1%, 7/170)、FLT3-ITD (2.9%, 5/170), IDH1 (1.7%, 3/170) and c-KIT (0.58%, 1/170). The most common coexisting mutations were TET2 (5/23). The RUNX1-mutated group showed significantly higher leukocyte levels, higher percentages of blast cells, higher incidences of leukemia transformation and lower platelet counts in comparison with RUNX1 non-mutation group (P＜0.05). whereas there were no statistically significant difference in age, MDS subtype, karyotype and hemoglobin level between 2 groups (P＞0.05). Seventeen patients harboring RUNX1 mutations were followed up and almost 47.05% (8/17) of the patients progressed into acute myeloid leukemia (AML). The rates of transformation into AML in ASXL1-mutation group was significantly higher than that in ASXLL- non-mutation group (47.05% vs 11.7%) (P=0.001).@*CONCLUSION@#The incidence of RUNX1 mutation is high in MDS patients. The RUNX1-mutated patients have higher leukocyte level, higher percentages of blast cells, higher incidences of leukemia transformation and lower platelet count.

Mechanism of Anti Apoptosis and Immune Evasion in Drug-Resistant Leukemia Cells Mediated by STAT3 / 中国实验血液学杂志

OBJECTIVE@#To investigate the mechanisms of anti-apoptosis and immune evasion in drug-resistant leukemia cells mediated by STAT3, further to explore the possible mechanism of leukemia relapse caused by minimal residual.@*METHODS@#Drug-resistance leukemia cell line was established by transfecting pcDNA3.1-STAT3 into K562 cells (K562/STAT3). The expression of STAT3, BAX and NKG2D ligands (MICA and ULBP1) in K562/-cells, K562/STAT3 were detected by Western blot and/or RQ-PCR. Cells apoptosis and the killing effect of NK cells on leukemia cells were detected by flow cytometry.@*RESULTS@#The expression of the total STAT3, STAT3 phosphorylation in K562/STAT3 was significantly increased, and P-gp mRNA expression was increased also significantly (P<0.005). In K562/STAT3 cells, the expression of pro-apoptotic BAX (P=0.005) was significantly lower, and the number of apoptotic cells (P=0.002) induced by adriamycin was significantly decreased as compared with those in K562/- cells. After K562/STAT3 cells were treated by STAT3 inhibitor (SH-4-54), the expression of BAX mRNA (P=0.017) was significantly higher and the number of apoptotic cells (P=0.005) was significantly increased. The MICA and ULBP1 mRNA expression in K562/STAT3 cells was significantly lower than that in K562/- cells, and also for MICA and ULBP1 protein (MICA and ULPB1 mRNA: P<0.0001, MICA protein: P=0.001, ULPB1 protein: P=0.022). After K562/STAT3 cells were treated with STAT3 inhibitor (SH-4-54), the expression of MICA mRNA and protein was increased (mRNA: P=0.001, protein: P=0.002), but ULBP1 mRNA and protein showed no significantly change (mRNA: P=0.137, protein: P=0.1905). The cytotoxicity of NK cells to K562/STAT3 cells was susceptible as compared with K562/- (P=0.002), but the cytotoxicity of K562/STAT3 cells to NK cell could be recovered by STAT3 inhibitor (P=0.006).@*CONCLUSION@#STAT3 phosphorylation can inhibits cell apoptosis and promotes cell immune escape. STAT3 inhibitors can promote the apoptosis of leukemia cells and increase their sensitivity to NK cells.

Coexisting Mutations in IDH1/2-Mutated Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the coexisting mutations in IDH-mutated acute myeloid leukemia(AML) and its relation with partial clinical parametrs.@*METHODS@#The exon 4 mutation of IDH1/2 gene was screened by using genome DNA-PCR combined with sanger sequencing, 51 targeted gene mutations in the patients with IDH1/2 mutation were detected by using high throughput DNA sequencing combined with sanger sequencing.@*RESULTS@#Among 358 patients, the IDH1/2 mutation was found in 46 cases including IDH1 mutation in 35 cases and IDH2 mutation in 11 cases, 97.87%(45/46) patients with IDH1/2 mutation simultaneously carried other gene mutations including 8(17.8%) cases with mutation of double gene, 17(37.8%) cases with mutation of 3 genes and 20(44.4%) cases with mutation of ≥ 4 genes. The mutation frequency of each patient averaged 3.52 times. In mutation of accompanied genes, the common genes were NPM1(n=29, 63.0%), next DNMT3A(n=25, 54.3%), FLT3-ITD(n=7, 15.2%), TET2(n=5, 10.9%) and NRAS(n=5, 10.9%). The average WBC level of patients with NPM1 mutation in IDH1 mutation group was higher than that of patients in wild type group(P<0.05). The complete remission (CR) rate of patients with DNMT3A mutation was significant lower than that of patients with wild type (30% vs 80%, P<0.01). The presence of ≥ 4 mutations was found to be significantly associated with higher white blood level than that in the patients with double mutations(P<0.05).@*CONCLUSION@#More than 95% AML patients with IDH1/2 mutation commonly show additional mutations. The number and the type of IDH coexisting mutations have certain effect on the clinical features and CR rate.

Neurophysiological predictors of aphasia recovery in patients with large left-hemispheric infarction: a mismatch negativity study / 中华医学杂志(英文版)

BACKGROUND@#Although the rehabilitation of aphasia has been extensively studied, the prediction of language outcome still has not received sufficient attention. The aim of this study was to predict the language outcome using mismatch negativity (MMN) in patients with large left-hemispheric infarction.@*METHODS@#MMN was elicited by an oddball paradigm in which a standard tone (1000 Hz) and deviant tone (1500 Hz) were presented at 90% and 10% of the number of tones, respectively. The mean amplitudes and laterality indexes (LIs) of MMN were measured over the prefrontal, frontal, central, parietal, temporal, and perisylvian electrodes and both hemispheres during the first 7 days (session 1) and 10 to 20 days (session 2) post-onset. Mixed three-way analysis of variance (ANOVA) was used to investigate differences in these factors between two aphasia groups (the good recovery group and poor recovery group). The predictive value of the most significant LI was also compared with the score of National Institutes of Health Stroke Scale score and low-density volume on computed tomography.@*RESULTS@#A total of 18 patients were enrolled in this study. Mixed three-way ANOVA showed no interaction effect of session × region of interest (ROI) × group (F [3.59, 57.38] = 1.301, P = 0.282) and no interaction effect of ROI × group (F [1.81, 29.01] = 0.71, P = 0.487) and session × group (F [1.00, 16.00] = 0.084, P = 0.776) for MMN amplitude. No interaction effect of session × ROI × group (F [1.79, 28.58] = 0.62, P = 0.530), but an interaction effect of session × group (F [1.00, 16.00] = 5.21, P = 0.036) was found for LIs. In the poor recovery group, the LIs of MMN over all the ROIs, except the parietal area, became more negative at session 2 than those at session 1 (P -0.36 over the perisylvian area suggested good recovery, but a score <-0.36 suggested poor recovery. The LI cut-off value of -0.36 had the highest sensitivity (90.0%) and specificity (87.5%) for predicting a good language outcome at 3 months post-stroke.@*CONCLUSION@#LIs of MMN amplitudes at approximately 2 weeks post left-hemisphere stroke serve as more sensitive predictors of language outcome, among which the LI over the perisylvian area exhibits the best predictive value.

Neurophysiological predictors of aphasia recovery in patients with large left-hemispheric infarction: a mismatch negativity study / 中华医学杂志(英文版)

Background@#Although the rehabilitation of aphasia has been extensively studied, the prediction of language outcome still has not received sufficient attention. The aim of this study was to predict the language outcome using mismatch negativity (MMN) in patients with large left-hemispheric infarction.@*Methods@#MMN was elicited by an oddball paradigm in which a standard tone (1000 Hz) and deviant tone (1500 Hz) were presented at 90% and 10% of the number of tones, respectively. The mean amplitudes and laterality indexes (LIs) of MMN were measured over the prefrontal, frontal, central, parietal, temporal, and perisylvian electrodes and both hemispheres during the first 7 days (session 1) and 10 to 20 days (session 2) post-onset. Mixed three-way analysis of variance (ANOVA) was used to investigate differences in these factors between two aphasia groups (the good recovery group and poor recovery group). The predictive value of the most significant LI was also compared with the score of National Institutes of Health Stroke Scale score and low-density volume on computed tomography.@*Results@#A total of 18 patients were enrolled in this study. Mixed three-way ANOVA showed no interaction effect of session × region of interest (ROI) × group (F [3.59, 57.38] = 1.301, P = 0.282) and no interaction effect of ROI × group (F [1.81, 29.01] = 0.71, P= 0.487) and session × group (F [1.00, 16.00]= 0.084, P= 0.776) for MMN amplitude. No interaction effect of session × ROI × group (F [1.79, 28.58] = 0.62, P = 0.530), but an interaction effect of session × group (F [1.00, 16.00] = 5.21, P = 0.036) was found for LIs. In the poor recovery group, the LIs of MMN over all the ROIs, except the parietal area, became more negative at session 2 than those at session 1 (P < 0.05), but this effect was not observed in the good recovery group. Additionally, significant differences were observed in the LIs at session 2 between the two groups (P < 0.05). The LI over the perisylvian area at session 2 had the highest predictive value with an area under the curve of 0.963 (95% confidence interval: 0.884–1.000). An LI score >-0.36 over the perisylvian area suggested good recovery, but a score <-0.36 suggested poor recovery. The LI cut-off value of-0.36 had the highest sensitivity (90.0%) and specificity (87.5%) for predicting a good language outcome at 3 months post-stroke.@*Conclusion@#LIs of MMN amplitudes at approximately 2 weeks post left-hemisphere stroke serve as more sensitive predictors of language outcome, among which the LI over the perisylvian area exhibits the best predictive value.

Effect of RNA Interference Targeting Gene Combined with Ultrasonic Irradiation and SonoVue Microbubbles on Proliferation and Apoptosis in Keratinocytes of Psoriatic Lesions / 中华医学杂志(英文版)

Background@#Signal transducer and activator of transcription 3 (STAT3) was strongly expressed and activated in psoriatic keratinocytes (KCs) and correlated with the severity of psoriasis. The study aimed to investigate the effects of STAT3 small interfering RNA (siRNA) combined with ultrasonic irradiation and SonoVue microbubbles on the proliferation and apoptosis in KCs of psoriatic lesions and the relative mechanisms.@*Methods@#Psoriatic KCs were transfected under four experimental conditions: (1) STAT3 siRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (LUS group); (2) STAT3 siRNA only carried by Lipofectamine 3000 (L group); (3) the negative control of siRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (siRNA-NC); (4) not treated as Blank. Cell Counting Kit-8 assay was used to evaluate the cell proliferation. Cell cycle analysis was detected with cycle test Plus DNA reagent kit associated with flow cytometer. FITC Annexin V apoptosis detection kit associated with flow cytometer was applied for apoptosis analysis. Fluo calcium indicator associated with flow cytometer was used to analyze intracellular free calcium concentration ([Ca]). The expressions of cyclin D1 and Bcl-xL were detected both at the mRNA level by real-time reverse transcription-polymerase chain reaction (RT-PCR) and at the protein level by Western blotting. The obtained data were statistically evaluated by two-way analysis of variance.@*Results@#STAT3 siRNA inhibited the growth of KCs in a time-dependent manner showing the highest proliferation inhibition in LUS group with proliferation ratio of 45.38% ± 5.85% at 72h (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced an altered cell cycle distribution of KCs showing the highest increases in G2/M-phase population up to 18.06% ± 0.36% in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced late apoptosis of KCs with the highest late apoptosis percentage of 22.87% ± 1.28% in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced the elevation of [Ca]of KCs with the highest calcium fluorescence intensity mean of 1213.67 ± 60.51 in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced the downregulation of cyclin D1 and Bcl-xL expressions of KCs at mRNA and protein levels with the lowest expressions in LUS group with cyclin D1 expression of 51.81% ± 9.58% and 70.17% ± 4.22% at mRNA level and at protein level, respectively, and with Bcl-xL expression of 37.58% ± 4.92% and 64.06% ± 7.78% at mRNA level and at protein level, respectively (P < 0.05 vs. L group, siRNA-NC, or Blank).@*Conclusions@#STAT3 siRNA inhibited the growth and induced the apoptosis in psoriatic KCs likely partly through altering cell cycle distribution, elevating [Ca], and downregulating cyclin D1 and Bcl-xL expressions. Silencing the target gene STAT3 in psoriatic KCs with siRNA combined with ultrasonic irradiation and microbubbles would contribute to a significant innovation as a new clinical therapy for psoriasis.

Improving rational use of antimicrobial agents by infection prevention and control / 中国感染控制杂志

Objective To evaluate the efficacy of infection prevention and control measures on the management of rational use of antimicrobial agents.Methods Patients who were admitted in a hospital from 2011 to 2015 were as the research object,a series of infection prevention and control intervention measure were taken,efficacy of intervention measures were evaluated.Results After the implementation of comprehensive intervention measures,compliance rate of hand hygiene increased year by year,from 38.17 ％ in 2011 to 87.16 ％ in 2015,difference was statistically significant (x2 =48.50,P＜0.05).Incidence of healthcare-associated infection dropped from 1.45％ to 1.06％,difference was statistically significant (x2 =42.50,P＜0.05);antimicrobial use density in 2011-2015 were 63.1,44.4,40.0,40.8,and 40.5 respectively,which showed a decreasing tendency.Conclusion Effective infection prevention and control measures have obvious effect on promoting management of rational use of antimicrobial agents,it is helpful for reducing the clinical use density of antimicrobial agents.

Comparison of Diagnosing and Staging Accuracy of PET (CT) and MIBG on Patients with Neuroblastoma: Systemic Review and Meta-analysis / 华中科技大学学报（医学）（英德文版）

To perform a systemic review and meta-analysis of the diagnostic accuracy of PET (CT) and metaiodobenzylguanidine (MIBG) for diagnosing neuroblastoma (NB),electronic databases were searched as well as relevant references and conference proceedings.The diagnostic accuracy of MIBG and PET (CT) was calculated for NB,primary NB,and relapse/metastasis of NB based on their sensitivity,specificity,and area under the summary receiver operating characteristic curve (AUSROC) in terms of per-lesion and per-patient data.A total of 40 eligible studies comprising 1134 patients with 939 NB lesions were considered for the meta-analysis.For the staging of NB,the per-lesion AUSROC value of MIBG was lower than that of PET (CT) [0.8064±0.0414 vs.0.9366±0.0166 (P＜0.05)].The per-patient AUSROC value of MIBG and PET (CT) for the diagnosis of NB was 0.8771±0.0230 and 0.6851±0.2111,respectively.The summary sensitivity for MIBG and PET (CT) was 0.79 and 0.89,respectively.The summary specificity for MIBG and PET (CT) was 0.84 and 0.71,respectively.PET (CT) showed higher per-lesion accuracy than MIBG and might be the preferred modality for the staging of NB.On the other hand,MIBG has a comparable diagnosing performance with PET (CT) in per-patient analysis but shows a better specificity.

Incidence of Atrial Fibrillation after Off-pump versus On-pump Coronary Artery Bypass Grafting: A Meta-analysis of Randomized Clinical Trials and Propensity Score Matching Trials / 华中科技大学学报（医学）（英德文版）

The association between atrial fibrillation (AF) after coronary artery bypass grafting (CABG) and the surgical techniques selected has been extensively reported.However,no consistent results were obtained.In the present study,a meta-analysis was conducted by searching the electronic databases PubMed,Embase,Web of Science,and Cochrane to identify the association of post-CABG AF with on-pump (conventional CABG,cCABG) or off-pump CABG (OPCABG).Outcomes from randomized clinical trials (RCTs) and propensity score matching (PSM) trials were pooled by using the fixed-effect or the random-effect modeling method,and verified by the quality-effect modeling method.There were 35 studies with 36 independent reports that met the inclusion criteria and were eventually included in our meta-analysis.The total odds ratio (OR) of the incidence of post-CABG AF between OPCABG and cCABG was 0.80 (95％ CI 0.71-0.91).The 25 randomized clinical trials (RCTs) had an OR of 0.69 (95％ CI 0.56-0.86),while the OR of the 11 PSM trials was 0.88 (95％ CI 0.77-1.00).Twenty-six studies involving the patients at a mean age no more than 65 years showed an OR of 0.76 (95％ CI 0.64-0.90),whereas 10 studies with patients greater than 65 years old showed an OR of 0.90 (95％ CI 0.78-1.05).The results of this meta-analysis suggest that OPCAB surgery may reduce the incidence of post-CABG AF when compared to cCABG and that younger patients may benefit more from OPCAB and have a lower incidence ofpost-CABG AF.

Association of HLA Alleles (A, B, DRB1) and HIV-1 Infection in the Han Population of Hubei, China / 华中科技大学学报（医学）（英德文版）

The HIV susceptibility and resistance alleles in the HLA genes were determined by investigating the distribution characteristics of the HLA alleles (A,B,and DRB1) in HIV-infected individuals of the Han population in Hubei,and by comparing these alleles with HIV-negative individuals from the same area.A cohort of 424 HIV-1 infected individuals were chosen as study subjects,and 836 HIV-negative healthy subjects from the same area served as the control population.HLA-A,B,and DRB 1 allele typing was performed using polymemse chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP) and polymerase chain reaction-sequencing based typing (PCR-SBT) techniques.Arlequin ver3.0 was used to analyze the allele and haplotype frequencies of HLA-A,B,and DRB l,whereas Epi Info 7 and SPSS18.0 was used to analyze the differences in the HLA alleles between the HIV-1 positive and HIV-1 negative groups.A*02:03,DRB1*01:01,and DRB1*15:01 alleles and their haplotypes as well as the HLA_Bw4-Bw6 hybrid showed a protective effect on HIV-1 infection.After adjusting for confounding factors such as age and sex,multivariate logistic regression analysis revealed that B* 15:02G,DRB 1*01:01,and DRB 1 * 15:01 subtypes were the resistance genes of HIV-1 infection,while B * 13:01 might increase susceptibility to HIV-1 infection.The correlation between A*02:06 and B*15:01G subtypes and HIV-1 susceptibility was independent of the age and sex of the host.This study demonstrated the influence of genetic factors in humans such as HLA polymorphism on individuals to resist HIV-1 infection.Association studies of HLA polymorphism,susceptibility/resistance to HIV-1 infection,and hosts' genetic background are of significant importance for research on HIV-1 pathogenesis and vaccine design.

Clinical observation of 577 nm panretinal photocoagulation on macular foveal retinal thickness on diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AlM: To investigate the influences of 577nm panretinal photocoagulation ( PRP ) on the retinal thickness of macular fovea on diabetic retinopathy ( DR) .METHODS:A total of 45 eyes of 37 cases suffering from preproliferative diabetic retinopathy ( PPDR ) and proliferative diabetic retinopathy ( PDR ) undergoing 577nm PRP were enrolled in this study. The alterations of the retinal thickness of macular fovea measured by optovue optical coherence tomography( OCT) before and 1, 3, 6mo following PRP were comparatively analyzed.RESULTS: The macularfoveal retinal thickness after 1, 3mo of PRP had significantly increased that before operation (P0. 05).CONCLUSlON: After the treatment of PRP, it appeared a transient increase on the retinal thickness of macular fovea, but after 6mo following-up, the macular foveal retinal thickness decreased nearly to the levels before PRP.

Analysis and application of game theory in estimating variable importance in linear model / 第二军医大学学报

Objective To apply Shapley value analysis of the game theory for evaluating the relative importance of the predictors in the linear regression when colinearity exists, and to provide a new concept of sequential importance partial R2. Methods Shapley value analysis of game theory(proposed by Shapley in 1953) was used to evaluate the influencing factors of hemoglobin(HB) in 757 normal adults, by regressing HB on four predictors including the white blood cell(WBC), red blood cell(RBC), blood platelet(PLT) and hematocrit(HCT); meanwhile, the sequential importance partial R2 was used to analyze its practical significance. Finally the estimated results of Shapley value was compared with others measures including traditional methods and recommended method. Results A succinct set of predictors including RBC, PLT and HCT was identified for establishing a multiply regression, with their relative importance values being 0.355 3, 0.012 4 and 0.553 8, respectively. The results of relative importance were consistent between Shapley value and dominance analysis. Moreover, it was found that the partial R2 of predictors had different marginal contributions in different orders. Conclusion HCT has the largest contribution to HB, followed by RBC, and PLT has the least effect to H.B. The order of contributions is consistent with the correlation matrix, indicating that the relative importance of the predictors in Shapley value is reasonable.

Roles of NKG2D in cytokine-induced killer (CIK) against hematological malignant cells lines / 中国实验血液学杂志

This study was purposed to investigate the CIK cell cytotoxicity to hematological malignant cell lines by interaction NKG2D receptors and corresponding ligands. The CIK cells was expanded from healthy individual with interferon (IFN)γ, CD3 monoclonal antibodies (mAb) and interleukin-2 (IL-2). The subset of lymphocyte and the expression of NK cell receptors on CIK cells was detected by flow cytometry; NKG2D ligand expression on hematological malignant cell lines was also analyzed by flow cytometry, the calcein acetoxymethyl ester (CAM) was used for labeling target cells, then the cytotoxicity of CIK cells to hematological malignant cell lines was detected by flow cytometry. The results showed that most of CIK cells expressed CD3 (97.85 ± 1.95%) , CD3(+)CD8(+) cells and CD3(+)CD56(+) cells increased significantly as compared with un-cultured cells (P < 0.001;P = 0.033). About 86% CIK cells expressed NKG2D receptor but no other NK receptors such as CD158a, CD158b and NCR. Different levels of NKG2D ligands were detected in hematological malignant cell lines U266, K562 and Daudi. CIK cells showed high cytotoxicity to these three different cell lines, and this cytotoxicity was partially blocked by treating CIK cells with anti-NKG2D antibody (U266 52.67 ± 4.63% vs 32.67 ± 4.81%, P = 0.008;K562 71.67 ± 4.91% vs 50.33 ± 4.91%, P = 0.007;Daudi 68.67 ± 5.04 vs 52.67 ± 2.60%, P = 0.024) . It is concluded that most of CIK cells express NKG2D receptor, interaction of NKG2D-NKG2D ligands may be one of the mechanisms, by which CIK cells kill hematological malignant cells.

Enhanced cytotoxicity against leukemia cells of natural Killer cells from cord blood after expansion in vitro / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the enhanced cytotoxicity against leukemia cells of natural Killer (NK) cells from cord blood (CB) after expansion in vitro.</p><p><b>METHODS</b>NK cells was expanded on a layer of trophoblast cells with irradiated K562-mb15-41BBL cell line for 21 days. The levels of receptors on NK cells were detected by flow cytometry. Cytotoxicity of expanded NK cells against leukemia cells and specific ligand of immunoglobulin like(Ig- liKe)receptors were assessed using 51Cr released assay.</p><p><b>RESULTS</b>There were no differences of inhibitory receptors expression between fresh NK cells and expanded NK cells [CD158a:(16.77±11.65)% vs(14.37±11.12)%, P>0.05; CD158b: (42.48±18.11)% vs (40.92±19.02)%, P>0.05; NKG2A: (70.20±18.43)% vs (78.90±13.69)%, P>0.05], but higher activated receptors expression on expanded NK cells [NKp30: (54.10±13.27)% vs (4.14±2.05)%, P<0.05; NKp44: (72.10±17.30)% vs (0.52±1.16)%, P<0.05; NKp46: (80.63±14.01)% vs (44.19±6.19)%, P<0.05; NKG2D: (97.50±2.55)% vs (72.25±14.35)%, P<0.05]. Expanded NK cells showed higher cytotoxicity against leuKemia cell lines than fresh NK cells [K562: (74.3±3.6)% vs (55.3±4.2)%, P<0.05; Raji: (60.6±5.0)% vs (12.0±3.6)%, P<0.05]. CD158a⁻ CD158b⁻ NK cells had higher cytotoxicity on four types of target cells, but CD158a⁺CD158b⁻ CB-NK cell had lower cytotoxicity on 221-Cw4 and 221-Cw3Cw4 cells. CD158a⁻ CD158b⁺ CB- NK cells had lower cytotoxicity on 221-Cw3 and 221-Cw3Cw4, but CD158a⁺CD158b⁺ CB-NK cells had higher cytotoxicity on 721- 221 cells.</p><p><b>CONCLUSION</b>Expression of activated receptors of expanded NK cells were up-regulated, but no changes of inhibitory receptors. Expanded NK cells showed high cytotoxicity against leukemia cells and kept the specificity of ligand of Ig-like receptors, which could be beneficial to cell-therapy for tumor.</p>

Ultrasonography of retroperitoneal ifbrosis / 中华医学超声杂志（电子版）

Objective To analyze the ultrasonographic features of retroperitoneal ifbrosis (RPF). Methods Totally 13 patients with retroperitoneal ifbrosis from February 2000 to October 2012 in the Long Gang central Hospital of Shenzhen were retrospectively analyzed. Results In all patients who underwent ultrasound examination, there were ten cases of idiopathic RPF and three cases of secondary RPF with abdominal tumors. In 11 cases, the masses were hypoechoic locating at retroperitoneum and surrounding the abdominal aorta without deifnitive margin. One case showed hypoechoic mass with clear boundary. In ten cases, the internal echogenicity of masses were uniform. In two cases, the internal echogenicity of masses were uneven with a small amount of ifbrous separator with slightly higher echogenicity. No blood was found in all masses. The encasement of inferior vena cava was found in three casesand the masses extended to iliac arteries in three cases. Hydronephrosis could be found in 11 patients (84.6%) and ureter dilatation was found in ten cases. Ureteral localized stenosis were found in two cases. Conclusion Ultrasonography is a preferred imaging method in diagnosing RPF.

Analysis of IDH1 and IDH2 mutations in patients with acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the prevalence of IDH gene (IDH1 and IDH2) mutations, types of mutations in patients with acute myeloid leukemia (AML), correlation with the internal tandem duplication(ITD) mutation of FLT3 gene, NPM1 gene mutation and some clinical characteristics.</p><p><b>METHODS</b>The mutations of IDH1 and IDH2 gene at exon 4, NPM1 gene at exon 12 and FLT3-ITD at exon 14 and 15 in 163 newly diagnosed AML patients were detected by PCR amplification followed by direct sequencing of genomic DNA.</p><p><b>RESULTS</b>(1) IDH mutations were found in 25 patients (25/163), and all were heterozygous, of which IDH1 in 7 patients (4.29%) and IDH2 in 18 (11.04%). A total of 4 types of IDH1 mutations were identified (c.395G→A, p.R132H, n = 4; c.394C→A, p.R132S, n = 1; c.394C→G, p.R132G, n = 1; c.315C→T, n = 1). The IDH1 mutation caused substitutions of residue R132 except for one (c.315C→T). All IDH2 mutations caused changes of R140 (c.419G→A, p.R140Q, n = 18). The incidence of IDH2 mutation was significantly higher than that of IDH1 mutation (11.0% v 4.3%, P = 0.022). Both IDH1 and IDH2 mutation were detected in one patient, while IDH1 was synonymous substitution (c.315C→T). IDH-mutated cases showed a significantly higher frequency of concurrent FLT3-ITD mutation compared with wildtype cases (34.6% vs 11.9%, P = 0.003), so did IDH mutations concurrent NPM1 mutation vs NPM1 wildtype (28.1% vs 12.7%, P = 0.033), of which the frequency of concurrent NPM1 and FLT-ITD mutations cases with the IDH mutation was significantly higher than that of NPM1 and FLT-ITD negative (45.5% vs 11.7%, P = 0.002). IDH mutation incidence was significantly higher in normal karyotype cases than in abnormal ones (20.5% vs 5.8%, P = 0.020). Patients with IDH mutations were significantly older than wildtype patients(P < 0.001), whereas, there were no statistically significant differences in gender, peripheral blood (PB) count at diagnosis between two groups.</p><p><b>CONCLUSIONS</b>The incidence of IDH mutation is higher in patients with de novo AMLs, of which IDH2 mutation more frequently, and the patients associated with older age, normal karyotype at diagnosis. IDH mutation has a strong association with NPM1 and FLT3-ITD mutations, suggesting that IDH mutation has synergistic effect with the latter gene on leukemogenesis.</p>

Research on frequency of application with modern Chinese herbal medicine / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the relationship between 500 kinds of commonly used Chinese herbal medicine and the classification of their efficacies in Chinese Materia Medica in relation to the common diseases listed in Internal Medicine.</p><p><b>METHODS</b>Database retrieval frequency of the quantitative statistical method was adopted. First, the 8 980 kinds of Chinese herbal medicine recorded in Chinese Materia Medica were used as the original search objects, and 4 493 kinds which were cited in more than five articles were picked out and then rechecked for further title citations. Second, as judged based on the Criterion, the numbers of articles which included the medicines in the line of standards were examined. As a result, 500 species of Chinese herbal medicine were singled out based on their retrieval frequency and were then used for compilation of the classification statistics according to their efficacy and the common diseases in Internal Medicine.</p><p><b>RESULTS</b>From the classification of Chinese medicines, herbs with wide efficiency and a meek nature had higher frequencies, but those which were not appropriate as decoctions had relatively lower frequencies. However, according to the average frequency, the Chinese herbal medicine for nourishing qi and tonifying blood, at 36,346 times and 34,544 times, respectively, were the most commonly used. Analyzed from the frequency of application of the Chinese medicine in the treatment of common diseases, most of the top 10 kinds of Chinese herbal medicine with the highest frequencies generally coincided with the 500 selected medicines. In addition, the Chinese medicines with clear pharmacological efficiency were easily isolated and purified to be made into injections, although other forms are more commonly used.</p><p><b>CONCLUSION</b>The results of the research objectively reflected the current applications of Chinese herbal medicine, and could be used as references in teaching, research, clinical applications, and in compiling and increasing the drugs in textbooks and Pharmacopoeia.</p>

Lead impairs ability of learning and memory and affects expression of synaptosomal-associated protein-25 in hippocampus of offspring / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To find the effects of lead taken by pregnant mice on learning and memory and the expression of synaptosomal-associated protein (SNAP)-25 mRNA and protein, in order to reveal the mechanism of neurotoxicity induced by lead.</p><p><b>METHODS</b>Lead exposure was conducted through freely drinking the corresponding lead acetate solutions with dosages of 0.3, 1.0, 3.0 g/L respectively. Each group was composed of 10 mice. 7, 14 and 21 days after their birth. The lead contents in blood and hippocampus of the offspring were determined. At the 21st day the expression of SNAP-25 mRNA and protein in hippocampus of all the offspring in various dosages groups were determined by RT-PCR and immunohistochemistry assay.</p><p><b>RESULTS</b>The lead contents in blood and hippocampus of various lead exposed groups were significantly higher than those of the control group (P < 0.05). The lead levels in blood and hippocampus changed accordingly to the days of growth. In Water Morris Maze experiment, the result of 0.3 g/L group was not significantly different from that of the control group (P > 0.05), however, the results of 1.0, 3.0 g/L groups (5.89 ± 0.54, 9.53 ± 1.03) were significantly different from those of the control group (1.73 ± 0.07) (P < 0.05, P < 0.01). The expression of SNAP-25 mRNA and protein was lower in lead exposed groups than that of the control group (P < 0.05).</p><p><b>CONCLUSION</b>Maternal lead exposure may induce the damage in the ability of learning and memory of the offspring. The neurotoxicity of lead may be induced by decreasing the expression of SNAP-25 mRNA and protein so as to affect the release of neurotransmitter from presynaptic terminal resulted in nerve damages.</p>