The effect and safety of first-line autologous hematopoietic stem cell transplantation in elderly patients with moderate/high-risk diffuse large B-cell lymphoma / 中华老年医学杂志

Objective:To investigate the efficacy and related influencing factors of autologous hematopoietic stem cell transplantation(auto-HSCT)as first-line consolidation therapy for newly diagnosed elderly patients with diffuse large B cell lymphoma(DLBCL).Methods:Retrospective study of clinical characteristics, therapeutic effect, and prognostic factors of newly diagnosed DLBCL elderly patients with an International Prognostic Index(IPI)score≥3 who underwent auto-HSCT in the Affiliated People's Hospital of Ningbo University from January 2015 to August 2020.Results:Among the 31 patients, 18 were males and 13 were females, with a median age of 65(60-75)years.The 13 cases(41.9%)were involved in 2 sites outside lymph nodes, and 13 cases(41.9%)were involved in bone marrow.IPI medium and high risk(IPI=3 points)was found in 21 cases(67.7%), high risk(≥4 points)in 10 cases(32.2%). Before transplantation, 21(67.7%)patients achieved complete remission(CR), and the other 10(32.3%)patients were in the partial remission(PR). All patients after transplantation achieved hematopoietic reconstitution.The median time for neutrophil and platelet engraftment were 10(9-16)days and 12(8-58)days respectively.During a median follow-up of 20.9(3.1 to 73.0)months after transplantation, transplant-related mortality within 100 days was 3.2%(1/31). The 2-year overall survival(OS)and progression-free survival(PFS)were(77.2±8.4)% and(72.7±8.3)%, respectively.Multivariate Cox analysis showed that the achieved partial remission status before auto-hematopoietic stem cell transplantation[OS( HR=30.064, 95% CI: 2.231-405.209, P=0.010), PFS( HR=9.165, 95% CI: 1.926-43.606, P=0.005)], and CD34 + cell count in graft <3×10 6/kg[OS( HR=12.004, 95% CI: 1.234-116.807, P=0.032), PFS( HR=6.115, 95% CI: 1.325-28.221, P=0.020)]were the independent poor prognostic factor affecting both OS and PFS in elderly lymphoma patients. Conclusions:Auto-HSCT may improve the survival rate of carefully selected elderly patients with DLBCL.Pretransplant disease status and the number of CD34 + cells in the graft are important factors to predict the efficiency of auto-HSCT of the patients.

Inhibitory effect of melatonin on pyroptosis of lens epithelium cells and its mechanism / 中华实验眼科杂志

Objective:To investigate the inhibitory effect of melatonin on pyroptosis of lens epithelium cells (HLECs) induced by hydrogen peroxide (H 2O 2) and its mechanism. Methods:The cultured HLECs were divided into normal control group, model control group, melatonin group, vitamin E group, and vitamin E solvent group.Cells in melatonin group, vitamin E group and vitamin E solvent group were pre-cultured with 1×10 -6 mol/L melatonin, 100 μmol/L vitamin E or equal volume of vitamin E solvent, then cultured with 100 μmol/L H 2O 2, respectively, and the cells in the normal control group and model control group were cultured with normal condition or 100 μmol/L H 2O 2, respectively.The HLECs transfected with nuclear factor erythroid 2-related factor 2 short hairpin RNA (shNrf2) or shNrf2 negtive control lentivirus and following with 100 μmol/L H 2O 2 treatment were served as shNrf2 group and shNrf2 negative control group, respectively; and the transfected cells treated with 1×10 -6 mol/L melatonin and subsequent 100 μmol/L H 2O 2 treatment were served as melatonin+ shNrf2 group and melatonin+ shNrf2 negative control group.The activity of lactic dehydrogenase (LDH) and the expression levels of interleukin (IL)-1β and IL-18 in the culture supernatant were detected by the enzyme linked immunosorbent assay (ELISA) kit.The concentration of reactive oxygen species (ROS) was assessed by flow cytometry.The expression level of Nrf2, NLRP3, apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), caspase-1 p20 and GSDMD-N proteins were evaluated by Western blot. Results:Compared with model control group, the activity of LDH and the concentrations of IL-1β and IL-18 were significantly decreased in melatonin group and vitamin E group, showing statistically significant differences (all at P<0.05). The ROS fluorescence intensities were 13 040.67±1 550.66 and 12 593.67±1 677.06 in melatonin group and vitamin E group, respectively, which were significantly lower than 18 310.33±1 248.01 in model control group (both at P<0.05). The relative expression levels of Nrf2 protein were 4.24±0.44 and 3.73±0.38 in melatonin group and vitamin E group, respectively, which were significantly higher than 2.28±0.34 in model control group, and the relative expression levels of NLRP3, ASC, caspase-1 p20 and GSDMD-N in melatonin group and vitamin E group were significantly decreased than model control group (all at P<0.05). The relative expression level of Nrf2 protein in shNrf2 group and melatonin+ shNrf2 group was significantly reduced, and the expression levels of LDH, IL-1β, IL-18, ROS content, NLRP3, ASC, caspase-1 p20 and GSDMD-N were significantly increased in comparison with shNrf2 negative control group and melatonin+ shNrf2 negative control group, respectively (all at P<0.05). Conclusions:Melatonin can inhibit the release of NLRP3 inflammasome by activating Nrf2, and has an inhibitory effect on the pyroptosis of HLECs.

Difference of clinical characteristics in ocular toxocariasis between adults and children and characteristics of anti-toxocaria antibody in intraocular fluids / 中华眼底病杂志

Objective:To compare the clinical manifestations of ocular toxoplasmosis (OT) in adult and children, and to preliminarily explore the role of intraocular fluid detection in the early diagnosis of OT.Methods:A retrospective study. From January 2018 to October 2019, 60 cases of OT patients with 60 eyes diagnosed in the Department of Ophthalmology of Beijing Chaoyang Hospital Affiliated of Capital Medical University were included in the study. The medical history information of patients was collected in parallel with slit-lamp microscopy, indirect ophthalmoscope examination, and canine toxoplasma antibody detection in aqueous or vitreous fluid. Fifty-eight cases underwent visual inspection; 2 cases did not underwent visual inspection, who were children. The visual acuity examination was carried out using the new version of the standard logarithmic visual acuity chart, which was converted into the logarithmic minimum angle of resolution(logMAR) visual acuity during statistics. According to age, the patients were divided into adult group and child group, with 12 eyes in 12 cases and 48 eyes in 48 cases, respectively. The clinical characteristics and main points of diagnosis and treatment of the two groups of patients were compared and observed. The comparison among the measurement data groups conforming and the normal distribution was performed by the independent t test. The comparison between the measurement data groups of the skewed distribution was performed by the Kruskal- Wallis test. The qualitative data were compared with χ 2 test. Results:Among the adult group and the child group, 7 (58.3%, 7/12) and 34 (70.8%, 34/48) patients with a clear history of contact with dogs and cats were in the adult group and the child group, respectively. The adult group was significantly lower than the child group, however, there was no different statistical significance ( χ 2=0.236, P=0.627). At the first visit, the self-reported blurred vision of the adult group and the child group was 10 (83.3%, 10/12) and 22 (45.8%, 22/48) cases, respectively. In the adult group and the child group, 3 (25.0%, 3/12) and 20 (43.5%, 20/46) eyes with logMAR visual acuity greater than 1.85, 8 (66.7%, 8/12) and 22 (45.8%, 22/46) eyes with logMAR visual acuity less than 0.3. The visual acuity of the adult group was better than that of the child group, and the difference was statistically significant ( Z=2.162, P=0.031). There was no statistically significant difference in the composition ratio of different clinical types of the two groups of eyes ( χ 2=1.908, P=0.385). The incidence of inflammation in the anterior segment of the eye in the adult group and the child group were 25.0% (3/12) and 56.3% (27/48), respectively; there was no statistically significant difference between the two groups ( χ 2=3.750, P=0.053). The concentration of antibodies in the vitreous humor of the affected eye in the adult group and the child group was greater than that of aqueous humor. The antibody concentrations of vitreous humor and aqueous humor were 36.51 (22.58) and 19.94 (21.78) U/ml in the children group; 45.95 (56.44) and 32.20 (38.64) U/ml in the adult group. Comparison of antibody concentrations in the vitreous humor and aqueous humor of the affected eyes in the child group showed statistically significant differences ( Z=-1.984, P=0.047). Conclusions:Compared with children with OT, adult patients with OT have better vision and mild inflammation or hyperplasia of the vitreous cavity. The detection of antibodies related to toxoplasma in the intraocular fluid is helpful for early diagnosis.

Clinical characteristics of 71 patients with coronavirus disease 2019 / 中南大学学报(医学版)

OBJECTIVES@#To analyze the clinical characteristics of 71 patients with coronavirus disease 2019 (COVID-19).@*METHODS@#The general data, epidemiological data, laboratory tests, imaging examinations, and treatment of 71 patients with COVID-19 admitted to the Sixth People's Hospital of Zhengzhou from January 19, 2020 to March 3, 2020 were retrospectively analyzed.@*RESULTS@#Of the 71 COVID-19 patients, the ages were 4-84 (41.29±15.21) years, 38 (53.5%) patients were male, 33 (46.5%) were female, and 52 (73.2%) were in 22 clusters. The main clinical manifestations were fever (78.9%), cough (64.8%), and sputum (38.0%). The fever was mainly low and moderate, with 49 patients (69.0%) at 37.3-39.0 ℃. Most of the leukocytes, neutrophils, and lymphocytes were normal, accounting for 47 (66.2%), 51 (71.8%), and 51 (71.8%) patients, respectively; a few of them were decreased, accounting for 21 (29.6%), 16 (22.5%), and 20 (28.2%) patients, respectively. There were 38 (53.5%) and 31 (43.7%) patients with the decreased CD4 and CD8 T cell counts, respectively. There were 41 (57.7%), 38 (53.5%), 32 (45.1%), 26(36.6%), 22 (31.0%), 20 (28.2%), 14 (19.7%), 14 (19.7%), and 9 (12.7%) patients with the increased levels of C-reactive protein, erythrocyte sedimentation rate, procalcitonin, fibrinogen,interleukin 6, lactate dehydrogenase,-dimer,alanine aminotransferase, and aspartate aminotransferase, respectively. Of the 71 patients, the lung was involved in 60 (84.5%) patients, the double lung was involved in 47 (66.2%) patients, and the single lung was involved in 13 (18.3%) patients. The course of the disease was long, and the time from symptom onset to the second severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid negative transformation was (17.22±6.34) days.There were no significant differences in the incubation period (=-0.453, >0.05), the complicates (χ=0.042, >0.05), and the time from symptom onset to diagnosis (=-1.330, >0.05) in patients between the non-severe group and the severe group. The onset age, gender, SARS-CoV-2 nucleic acid negative time, lymphocyte count, -dimer, C-reactive protein, total bilirubin, direct bilirubin, lactate dehydrogenase, calcium ion, CD4 T cell count, CD8 T cell count, calcitonin, procalcitonin, and troponin were significantly different between the severe group and the non-severe group (all <0.05). Among the 71 patients, 4 (5.6%) patients were mild, 59 (83.1%) were normal, and 8 (11.3%) were severe or critical.@*CONCLUSIONS@#The aggregation phenomenon of COVID-19 is obvious. Fever and cough are the main clinical manifestations. White blood cells, neutrophils, and lymphocytes in the most patients in the early onset are normal. Most COVID-19 patients are light and ordinary type, with good prognosis.

Effects of angiotensin converting enzyme inhibitor/angiotensin receptor blocker on clinical characteristics of coronavirus disease 2019 patients with hypertension / 中华内科杂志

Objective:To analyze the effects of angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) on coronavirus disease 2019 (COVID-19) patients with hypertension, and to provide an evidence for selecting antihypertensive drugs in those patients.Methods:Clinical data were retrospectively analyzed in 58 COVID-19 patients with hypertension admitted to Shanghai Public Health Clinical Center from January 20 to February 22, 2020, including epidemiological history, clinical manifestations, laboratory findings, chest CT and outcome. Patients were divided into ACEI/ARB group and non-ACEI/ARB group.Results:Twenty-six patients were in ACEI/ARB group and the other 32 patients in non-ACEI/ARB group, with median age 64.0 (49.5, 72.0) years and 64.0 (57.0, 68.8) years respectively. The median time to onset was 5(3, 8) days in ACEI/ARB group and 4 (3, 7) days in non-ACEI/ARB group, the proportion of patients with severe or critical illness was 19.2% and 15.6% respectively. The main clinical symptoms in two groups were fever (80.8% vs. 84.4%) and cough (23.1% vs. 31.3%). The following parameters were comparable including lymphocyte counts, C-reactive protein, lactate dehydrogenase, D-dimer, bilateral involvement in chest CT (76.9% vs. 71.9%), worsening of COVID-19 (15.4% vs. 9.4%), favorable outcome (92.3% vs. 96.9%) between ACEI/ARB group and non-ACEI/ARB group respectively (all P>0.05). However, compared with non-ACEI/ARB group, serum creatinine [80.49 (68.72, 95.30) μmol/L vs. 71.29 (50.98, 76.98) μmol/L, P=0.007] was higher significantly in ACEI/ARB group. Conclusions:ACEI/ARB drugs have no significant effects on baseline clinical parameters (serum creatine and myoglobin excluded) , outcome, and prognosis of COVID-19 patients with hypertension. Antihypertensive drugs are not suggested to adjust in those patients, but the potential impairment of renal function as elevation of serum creatinine should be paid attention in patients administrating ACEI/ARB drugs.

Breakthrough of invasive fungal disease with posaconazole as primary prophylaxis after induction chemotherapy for acute myeloid leukemia / 中华内科杂志

Objective:To investigate the breakthrough incidence of invasive fungal disease(IFD) and side effects of posaconazole as primary prophylaxis during induction chemotherapy for acute myeloid leukemia(AML).Methods:A total of 206 newly diagnosed AML patients admitted to our department during January 2016 and December 2018 were enrolled in the study. Exclusive criteria were as followings including patients diagnosed as acute promyelocytic leukemia; those who received intravenous antifungal therapy after admission or had history of IFD one month before induction chemotherapy, or those with functional insufficiency of vital organs and those older than 65. Forty-seven patients received posaconazole (posaconazole group), 61 cases received voriconazole (voriconazole group) and 98 cases did not receive any prophylaxis (control group) during induction chemotherapy. Prophylactic efficacy and safety between posaconazole and voriconazole were compared.Results:During induction chemotherapy, five possible cases of IFD occurred in posaconazole group (10.6%); while 11 cases (18.0%) were in voriconazole group including 7 possible, 3 probable and 1 proven. Thirty-five cases (35.7%) in control group were diagnosed as IFD including 19 possible, 11 probable and 5 proven ones. The incidences of IFD in posaconazole and voriconazole group were significantly lower than that in control group ( P<0.05). The difference of posaconazole group and voriconazole group was not significant ( P>0.05). The reported adverse events in posaconazole group were significantly lower than those in voriconazole group [12.8%(6/47) vs. 32.8%(20/61), P<0.05]. Conclusions:Posaconazole and voriconazole decrease IFD as primary prophylaxis during induction chemotherapy in patients with AML. The prophylactic effect of IFD with posaconazole is similar as voriconazole, but posaconazole shows better safety.

Breakthrough of invasive fungal disease with posaconazole as primary prophylaxis after induction chemotherapy for acute myeloid leukemia / 中华内科杂志

Objective@#To investigate the breakthrough incidence of invasive fungal disease(IFD) and side effects of posaconazole as primary prophylaxis during induction chemotherapy for acute myeloid leukemia(AML).@*Methods@#A total of 206 newly diagnosed AML patients admitted to our department during January 2016 and December 2018 were enrolled in the study. Exclusive criteria were as followings including patients diagnosed as acute promyelocytic leukemia; those who received intravenous antifungal therapy after admission or had history of IFD one month before induction chemotherapy, or those with functional insufficiency of vital organs and those older than 65. Forty-seven patients received posaconazole (posaconazole group), 61 cases received voriconazole (voriconazole group) and 98 cases did not receive any prophylaxis (control group) during induction chemotherapy. Prophylactic efficacy and safety between posaconazole and voriconazole were compared.@*Results@#During induction chemotherapy, five possible cases of IFD occurred in posaconazole group (10.6%); while 11 cases (18.0%) were in voriconazole group including 7 possible, 3 probable and 1 proven. Thirty-five cases (35.7%) in control group were diagnosed as IFD including 19 possible, 11 probable and 5 proven ones. The incidences of IFD in posaconazole and voriconazole group were significantly lower than that in control group (P<0.05). The difference of posaconazole group and voriconazole group was not significant (P>0.05). The reported adverse events in posaconazole group were significantly lower than those in voriconazole group [12.8%(6/47) vs. 32.8%(20/61), P<0.05].@*Conclusions@#Posaconazole and voriconazole decrease IFD as primary prophylaxis during induction chemotherapy in patients with AML. The prophylactic effect of IFD with posaconazole is similar as voriconazole, but posaconazole shows better safety.

Ikaros family zinc finger 1 mutation is a poor prognostic factor for adult Philadelphia chromosome positive acute lymphoblastic leukemia / 中华内科杂志

Objective To analyze the prognostic impact of Ikaros family zinc finger 1(IKZF1)mutation on adult Philadelphia chromosome (Ph1) positive acute lymphoblastic leukemia (ALL) patients.Methods IKZF1 mutation was detected in 63 adult Phi positive ALL patients at diagnosis using capillary electrophoresis.Recruited patients were treated in our center and other three hospitals in Ningbo from January 2014 to January 2017.Clinical data were collected and retrospectively analyzed.Results Thirty-nine (61.9％) patients were positive IKZF1 mutation in this cohort.The white blood cell (WBC) count in IKZF1 mutation group was significantly higher than that of mutation negative group [(64.6±11.3)× 109/L vs.(33.7±5.6)×109/L,P＜0.05].Patients with WBC count over 30×109/L accounted for 56.4％ in IKZF1 mutation group.Complete remission (CR) rate in the IKZF1 mutation group was also lower than that of negative group after induction chemotherapy (64.1％ vs.75.0％,P＞0.05).IKZF1 was a negative prognostic factor but not independent factor for survival by univariate and multivariate analyses.Patients were divided into chemotherapy and allogeneic transplantation groups.The 3-year overall survival (OS) rate and 3-year leukemia-free survival (LFS) rate in IKZF1 mutation group were significantly lower than those of negative group in both transplantation group (42.3％ vs.59.3％;31.2％ vs.50.0％;respectively,both P＜0.05) and chemotherapy group (24.8％ vs.40.0％;19.0％ vs.34.3％;respectively,both P＜0.05).Conclusion IKZF1 mutation is a poor prognostic factor for adult Ph1 positive ALL patients.

Effect of FLT3-ITD with DNMT3A R882 double-mutation on the prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To investigate the impact of FLT3-ITD and DNMT3A R882 double mutations to the prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#FLT3-ITD, DNMT3A, C-kit, CEBPA, FLT3-TKD and NPM1 mutations were detected in 206 newly diagnosed AML patients by Sanger sequencing (M3 and those received FLT3 inhibitor were excluded). Clinical data of AML patients were retrospectively analyzed to compare the prognosis of each gene mutation group.@*Results@#①Of 206 patients, 104 were male and 102 female with a median age of 38 (3-63) years, including 6 cases of M0, 24 cases of M1, 56 cases of M2, 39 cases of M4, 63 cases of M5, 6 cases of M6 and 12 unclassified cases. ②All 206 patients were divided into four groups according to the mutation gene at the time of diagnosis: FLT3-ITD+ DNMT3A R882+ group (group A), FLT3-ITD+ DNMT3A R882- group (group B), FLT3-ITD- DNMT3A R882+ group (group C) and FLT3-ITD- DNMT3A R882- groups (group D). Gender, leukocyte count at diagnosis, chromosome karyotype, the median age, FAB classification, disease status prior to transplantation, type of donor, conditioning regimen and GVHD were not significantly different between four groups (P>0.05). ③The 2-year cumulative recurrence rate (CIR) of group A was significantly higher than that of other groups [group A (72.2±2.6)%, group B (38.6±0.6)%, group C (36.8±1.6)%, group D (27.8±0.1)%, respectively, P<0.05], while the 2-year overall survival (OS) rate and 2-year leukocyte-free survival (LFS) rate were lower than those of other groups [group A (30.9±13.3)%, (11.3±10.2)%; group B (67.5±7.8)%, (47.9±8.4)%; group C (61.4±12.4)%, (56.8±12.5)%; group D (80.1±3.7)%, (79.7±3.6)%, respectively, P<0.05].@*Conclusion@#AML patients with FLT3-ITD and DNMT3A R882 double mutations had a very high CIR and low OS, LFS after transplantation.

Clinical Observation of Safflower Yellow Pigment in the Treatment of Elderly Patients with Diabetic Ne-phropathy Complicated with Acute Myocardial Infarction / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of safflower yellow pigment in the treatment of elderly pa-tients with diabetic nephropathy complicated with acute myocardial infarction. METHODS:A total of 102 elderly patients with dia-betic nephropathy complicated with acute myocardial infarction were selected from our hospital during Jan. 2013-Jun. 2015,and then divided into observation group(52 cases)and control group(50 cases)according to random number table. Control group was given routine treatment as anticoagulation,regulating blood lipid,controlling blood glucose and blood pressure. Observation group was additionally given Safflower yellow pigment for injection 150 mg added into 0.9% Sodium chloride injection 250 mL,ivgtt, qd,on the basis of control group. Both groups received treatment for 2 weeks. Clinical efficacies of 2 groups were observed. Renal function indexes(UMA,Scr,BUN,TC,TG),cardiac function indexes(EF,SV,CO,CI),inflammatory factors(CRP,IL-6, TNF-α)and hemorheological indexes(whole blood high-shear viscosity,whole blood low-shear viscosity,hematocrit,fibrinogen and platelet aggregation rate)were compared between 2 groups before and after treatment. The occurrence of ADR was recorded in 2 groups. RESULTS:Total response rate of observation group was 96.15%,which was significantly higher than 88.00% of control group,with statistical significance(P<0.05).Before treatment,there was no statistical significance in renal function indexes,cardiac function indexes,inflammatory factors or hemorheological indexes between 2 groups(P>0.05).After treatment,renal function index-es,inflammatory factors and hemorheological indexes of 2 groups were decreased significantly,while cardiac function indexes were in-creased significantly;above indicators of the observation group was significantly better than control group,with statistical significance (P<0.05).No obvious ADR was found in 2 groups.CONCLUSIONS:Safflower yellow pigment shows significant therapeutic effica-cy for elderly patients with diabetic nephropathy complicated with acute myocardial infarction,can significantly improve renal function and cardiac function,decrease inflammatory factor levels and improve hemorheological indexes with good safety.

Imaging of endolymphatic spaces of internal ear in aged patients suffering from Meniere's disease / 中华老年医学杂志

Objective The research aimed at evaluating whether non-invasive endolymphatic MR imaging could be used in aged patients(≥60 years)suffering from Meniere's disease.Methods Under guidance of nasal endoscopy,a diluted gadopentetate dimeglumine injection was administrated through eustachian tube into mid-ear cavity in four patients (≥60 years old) suffered from Meniere's disease.3D-FLAIR MRI scan was performed one day after the administration.Results The administration succeeded through eustachian tube into mid-ear cavity in those four patients.A rise of fluid level on tympanic membrane while administrating a diluted gadopentetated meglumine injection was observed.Imaging of inner ear endolymphatic spaces were visible in vestibule and cochlea in imaging of patient 1.As to patient 2,in cochlea the scala tympani of the first and second turns were enhanced while scala vestibule weren't;Vestibules couldn't be recognized.In images of patient 3,the scala tympani of the three turns in cochlea were enhanced while scala vestibule weren't;Vestibules couldn't be recognized.For Patient 4,in cochlea the scala tympani of the first turn were enhanced while scala vestibule weren't,and the second turn was partially enhanced;and endolymphatic space of vestibule could be distinguished from perilymphatic space.Conclusions This technique could be adopted in investigation of Meniere's disease in elderly patients.MR imaging of endolymphatic spaces in vestibule and cochlea can be visualized,which may partially provide data for diagnosis of Meniere's disease.

Expression of FGFR3 in acute lymphoblastic leukemia patients and its contribution to proliferation of circulating endothelial cells / 中国病理生理杂志

AIM: To evaluate the expression of fibroblast growth factor receptor 3 (FGFR3) in acute lymphocytic leukemia (ALL) patients and its contribution to the proliferation of circulating endothelial cells (CECs).METHODS: The mRNA expression levels of FGFR3 in 44 patients with ALL were assayed by RT-PCR.Overall survival (OS) rates of the patients in FGFR3+ group and FGFR3-group were estimated by Kaplan-Meier analysis.The CECs were sorted from peripheral blood by magnetic-activated cell sorting and then counted by 3-color flow cytometry.The cell counts, antigen expression, growth curve and colony forming rate of the CECs in the 2 groups were determined.The FGFR3 expression of CECs was identified by immunofluorescence staining.RESULTS: The positive rate of FGFR3 mRNA expression was 43.2% in 44 ALL patients with normal karyotype.T-ALL expressed higher level of FGFR3 than B-ALL (P<0.05).FGFR3 was over-expressed in ALL patients with bone marrow blast proportion ≥5% (P<0.05).The probability of OS was significantly lower in FGFR3+ group than that in FGFR3-group (P<0.05).The sorted CECs highly expressed CD31, CD144, VEGFR-2 and CD146, and rarely expressed CD45.The counts of CECs and expression level of CD133 significantly increased in FGFR3+ group compared with FGFR3-group.The same result of the amount of colony formation was observed (P<0.05).There was significant difference at 3 time points of cultured CECs count in vitro between FGFR3+ group and FGFR3-group (P<0.05).The positive rate of FGFR3 expression of CECs from 19 ALL-FGFR3+ patients was (29.00±15.71)%.CONCLUSION: The over-expression of FGFR3 gene in ALL may be helpful to evaluate the prolife-ration of CECs, and become a double target with anti-tumor and anti-angiogenesis effects to offer more choice for molecular therapy in the future.

Clinical investigation of sequential therapy with micafungin and reduced -dose voriconazole in prevention of fungal in patients after allogeneic hematopoietic stem cell transplantation / 中国基层医药

Objective To observe the clinical effect of sequential therapy with micafungin and reduced -dose voriconazole in prevention of invasive fungal infections in patients received allogeneic hematopoietic stem cell transplantion (Allo -HSCT).Methods 28 patients received the treatments for prevention of fungal infection with micafungin 50 mg per day from pretreatment to 30 days,then oral voriconazole at a dose of 1 00 mg two times per day until 90 days after Allo -HSCT.The occurrence of invasive fungal infection and the side effects of both medicine were observed during 1 80 days after Allo -HSCT.Results 8 patients(28.6%)developed above grade 2 acute graft verse host disease(GVHD),2 patients developed grade 3 GVHD among the 8 patients.Two case with GVHD were cured by voriconazole with the therapeutic dose who occurred probably pulmonary invasive fungal infection at two months after Allo -HSCT.There were no other patients diagnosed fungal infection.No toxic efect were observed during the clinical observation during treatment with micafungin.5 patients appeared mild liver function abnormalities during treatment with voriconazole,and liver dysfunction were improved by symptomatic treatment.2 cases developed transient auditory hallucination and visual impairment induced by voriconazole.Conclusion Micafungin and reduced -dose voricon-azole are effective and safe prophylaxis in prevention early invasive fungal infection after HSCT.

Serum miR-146a as potential biomarker for sepsis / 实用医学杂志

Objective To study the expression of miR-146a in the serum of sepsis and the diagnostic value.Methods Serum miR-146a expression was detected in 98 patients diagnosed with sepsis,69 patients with severe sepsis and 30 healthy controls.ROC plots were used to evaluate the diagnostic value.Results The expression of miR-146a was decreased successively in healthy group,general sepsis group and severe sepsis group.In the diagnosis of sepsis,at the optimal expression cutoff miR-146a value of 0.805,the sensitivity was 0.967 and specificity 0.940,with an AUC of 0.983.In the diagnosis of sepsis severity degree,at the optimal expression cutoff miR-146a value of 0.530,the sensitivity was 0.796 and specificity 0.986,with an AUC of 0.943.Conclusion miR-146a can be a potential marker in diagnosis of sepsis and severity degree .

Clinical Observation of Safflower Yellow Pigment in the Treatment of Elderly Patients with Diabetic Ne-phropathy Complicated with Acute Myocardial Infarction / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of safflower yellow pigment in the treatment of elderly pa-tients with diabetic nephropathy complicated with acute myocardial infarction. METHODS:A total of 102 elderly patients with dia-betic nephropathy complicated with acute myocardial infarction were selected from our hospital during Jan. 2013-Jun. 2015,and then divided into observation group(52 cases)and control group(50 cases)according to random number table. Control group was given routine treatment as anticoagulation,regulating blood lipid,controlling blood glucose and blood pressure. Observation group was additionally given Safflower yellow pigment for injection 150 mg added into 0.9% Sodium chloride injection 250 mL,ivgtt, qd,on the basis of control group. Both groups received treatment for 2 weeks. Clinical efficacies of 2 groups were observed. Renal function indexes(UMA,Scr,BUN,TC,TG),cardiac function indexes(EF,SV,CO,CI),inflammatory factors(CRP,IL-6, TNF-α)and hemorheological indexes(whole blood high-shear viscosity,whole blood low-shear viscosity,hematocrit,fibrinogen and platelet aggregation rate)were compared between 2 groups before and after treatment. The occurrence of ADR was recorded in 2 groups. RESULTS:Total response rate of observation group was 96.15%,which was significantly higher than 88.00% of control group,with statistical significance(P<0.05).Before treatment,there was no statistical significance in renal function indexes,cardiac function indexes,inflammatory factors or hemorheological indexes between 2 groups(P>0.05).After treatment,renal function index-es,inflammatory factors and hemorheological indexes of 2 groups were decreased significantly,while cardiac function indexes were in-creased significantly;above indicators of the observation group was significantly better than control group,with statistical significance (P<0.05).No obvious ADR was found in 2 groups.CONCLUSIONS:Safflower yellow pigment shows significant therapeutic effica-cy for elderly patients with diabetic nephropathy complicated with acute myocardial infarction,can significantly improve renal function and cardiac function,decrease inflammatory factor levels and improve hemorheological indexes with good safety.

Alteration of circulating endothelial cells from acute promyelocytic leuke-mia patients before and after treatment and its influential factors / 中国病理生理杂志

AIM:To determine the biological feature of circulating endothelial cells (CECs) in acute promye-locytic leukemia ( APL) patients before and after treatment , and to analyze the relationship between CECs and the clinical characteristics .METHODS: The CECs were sorted from peripheral blood by magnetic-activated cell sorting and then counted by 3-color flow cytometry.The cells were identified by immunofluorescence staining for the expression of CD 146, CD31, CD144, VEGFR-2, CD45 and CD133.The CECs were cultured in vitro, and the tube formation and colony-forming rate were determined .RESULTS:Increased quantity of CECs was observed in CD 34 positive group and group with WBC >10 ×109/L (P<0.05).The quantity of CECs had a significant difference among low risk , medium risk and high risk groups (P<0.05).The positive rate of CD133 and quantity of CECs significantly reduced in 32 APL patients when they gain complete remission after treatment (P<0.05).The amount of tube formation and colony-forming rate were significant-ly reduced after treatment (P<0.05).The ratio of CECs quantity from APL patients after treatment to that before treatment had a negative correlation with arsenic concentration in urine on day 7 during As2O3 treatment (P<0.05).CONCLU-SION:Accurately counting CECs may be helpful for evaluating prognosis and designing treatment strategy .

Evaluation of the diagnostic value of Xpert Mycobacterium tuberculosis/rifampin assay in extrapulmonary ;tuberculosis / 中华传染病杂志

Objective To detect Mycobacterium tuberculosis (MTB)and its resistance against rifampin (RIF ) by applying Xpert MTB/RIF assay in the clinical samples from patients with extrapulmonary tuberculosis,and to discuss the value of this assay in extrapulmonary tuberculosis. Methods Totally 300 clinical samples from the patients who were highly suspected with extrapulmonary tuberculosis and hospitalized in Department of Tuberculosis Section,Shanghai Public Health Clinical Center of Fudan University from May 2014 to May 2015 were collected.Smear and fluorescence staining microscopy,MGIT 960 BACTEC liquid culture,Xpert MTB/RIF assay were applied to detect MTB in these samples.Meanwhile,all the patients received the peripheral blood T-cell spot of tuberculosis test (T-SPOT.TB).The sensitivity and specificity of Xpert MTB/RIF assay for MTB and its resistance against rifampin (RIF)in extrapulmonary tuberculosis samples were evaluated.The measurement data of two independent samples were analyzed by using t test and enumeration data were analyzed by usingχ2 test.Results Totally 282 out of 300 clinical samples from patients with extrapulmonary tuberculosis were included in this study,and 62.7% were male with average age of (32.1 ±24.6 )years and 37.3%were female with average age of (37.8 ±21 .0)years.When MGIT 960 BACTEC liquid culture results were considered as standard diagnosis,the sensitivity,specificity,positive predictive value and negative predictive value of Xpert MTB/RIF assay were 53.8% (95 %CI :37.4%—69.6%),100.0% (95 %CI :86.3%—100.0%),100.0% (95 %CI :80.8%—100.0%)and 63.3% (95 %CI :48.3%—76.2%), respectively.The sensitivity of Xpert MTB/RIF assay in smear-positive/culture-positive samples was 92.3% (95 %CI :62.1 %— 99.6%),while that in smear-negative/culture-positive samples was only 34.6% (95 %CI :17.9%— 55 .6%).Xpert MTB/RIF assay had advantage for detecting MTB in fine needle aspirates,pus,stool and urine,but not in serous effusion and cerebrospinal fluid.However,the sensitivities of MGIT BACTEC 960 liquid culture,fluorescence smear and T-SPOT.TB were 25 .8%, 21 .8% and 70.2%,respectively,and the specificities were 95 .5 %,90.3% and 51 .6%,respectively. The diagnostic value of Xpert MTB/RIF assay was not significantly different from those of MGIT BACTEC 960 liquid culture and fluorescence smear (χ2 =0.61 and 3.45 ,respectively;both P >0.05 ), while it was significantly different from T-SPOT.TB (χ2 =50.58,P <0.05).The sensitivity of T-SPOT. TB was significantly superior to Xpert MTB/RIF assay,but the specificity was relatively low.The sensitivity and specificity of Xpert MTB/RIF assay in RIF resistance detection were 71 .4% (95 %CI :30.3%—94.9%)and 100.0% (95 %CI :86.7%—100.0%),respectively.Conclusions The sensitivity and specificity of Xpert MTB/RIF assay in detecting MTB in fine needle aspirates,pus,stool and urine are relatively high,but not in serous effusion and cerebrospinal fluid.However,the pros of rapid detection and the ability of detecting RIF resistance are useful for the diagnose of extrapulmonary tuberculosis in clinical settings.

DNA methylation-mediated epigenetic silencing of miR-720 contributes to leukemogenesis in acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression level and regulation mechanism of miR-720 as well as the association of miR-720 expression with leukemia biological characteristics.</p><p><b>METHODS</b>Expression and promoter methylation of miR-720 were determined by quantitive PCR and pyrosequencing in 38 patients with AML and 20 normal controls. Lentivirous-mediated miR-702 overexpression was constructed in AML cell line kasumi-1. The cell proliferation, apoptosis, cycle, colony formation, migration and P53-mediated apoptosis pathway were determined.</p><p><b>RESULTS</b>AML patients showed significantly lower miR-720 expression compared with normal controls (0.69±0.09 vs 3.00±0.46, P<0.01); The methylation level of miR-720 promoter region in AML patients were significantly higher than normal controls [(75.56±2.35)% vs (47.65±2.78)%, P<0.01]. miR-720 overexpression in kasumi-1 cells induced significantly increased cell apoptosis (P=0.017), elevated apoptosis sensitivity to etoposide (P=0.004), and reduced cell proliferation (P<0.01). miR-720 overexpression also induced reduced colony formation (P=0.005), cell cycle arrest in G(1)/G(0) phase and decreased migration ability in kasumi-1 cells. In addition, overexpression of miR-720 significantly induced increased cell apoptosis-related proteins including P53 and Bax, and activation of NF-κB signal transduction pathway. After kasumi-1 cells were treated with 1uM decitabine for 48 hours, miR-720 promoter methylation reduced significantly, and miR-720 expression significantly increased.</p><p><b>CONCLUSION</b>The expression of miR-720 in AML patients reduced significantly, and DNA methylation-mediated epigenetic silencing of miR-720 contributed to maintain the malignant characteristics of AML.</p>

Influence of protein kinase Cε on biological behavior of hepatic cancer SK-Hep-1 cells / 中国病理生理杂志

AIM:To investigate the inhibitory effect of small interfering RNA ( siRNA) on the expression of protein kinase Cε( PKCε) in human hepatoma SK-Hep-1 cells, and the biological behaviors of the transduced cells , inclu-ding proliferation and invasion , were investigated.METHODS:The cultured SK-Hep-1 cells were divided into 3 groups, including PKCε-siRNA group , negative control ( NC)-siRNA group and control group .MTT assay was used to analyze the proliferation of the SK-Hep-1 cells in the respective groups , while invasion potency was determined by Transwell assay .The protein levels of functional biomarkers such as Ki 67 and matrix metalloproteinase 9 ( MMP-9 ) were measured by Western blotting .The Luciferase reporter gene assay was used to explore the activity of the NF-κB pathway .RESULTS:PKCεex-pression in SK-Hep-1 cells transfected with PKCε-siRNA was significantly down-regulated at both mRNA and protein levels compared with that in the normal SK-Hep-1 cells (P<0.01), with the decreases in the protein levels of Ki67 and MMP-9. The invasion and proliferation of SK-Hep-1 cells were obviously inhibited in PKCε-siRNA group compared with control group (P<0.01).Furthermore, the transcriptional activity of NF-κB was down-regulated when PKCε was effectively in-hibited by PKCε-siRNA (P<0.01).CONCLUSION:Down-regulation of PKCεinhibits the proliferation and invasion of hepatic carcinoma cells , which might be mediated via the NF-κB signaling pathway .

Effects of Shuxuetong injection combined with edaravone injection on neurological, sermn lipid, C-reactive protein and interleukin 6 levels in serum of patients with acute cerebral infarction / 国际中医中药杂志

Objective To observe effects of shuxuetong injection combined with edaravone injection on the neurological, sermn lipid, c-reactive protein and interleukin 6 Levels in serum in patients with acute cerebral infarction. Methods 100 patients with acute cerebral infarction were randomly recruited into a control group and a treatment group by means of random number table. The control group was treated with 30mg edaravone injection, which was added to 100 ml normal saline, twice a day, continuous therapy for 14 days, and the treatment group was treated with 6mg shuxuetong injection, which was added to 2S0 ml normal saline, once a day, continuous therapy for 14 days based on the control group. The neurological was observed, triglyceride (TG) , cholesterol (TO , low density lipoprotein cholesterol (LDL-C) , high density lipoprotein cholesterol (HDL-C) , c-reactive protein and interleukin 6 Levels in serum were detected before and after the treatment.Results Compared with the control group, neurological deficit score, c-reactive protein and interleukin 6 Levels in serum in the treatment group decreased significantly (χ2=4.351, 3.81, 3.617 respectively, P<0.05) .TG, TC, LDL-C in serum in the treatment group were lower than that of the control group (χ2=2.135,P<0.01; χ2=3.061, 3.655, P<0.05 ); HDL-C in serum was higher than that of the control group (χ2=2.762,P<0.01) . The total effective rate of the treatment group and the control group was 86.0% and 66.0% respectively, there was a significant difference (χ2=3.393, P<0.05) . Conclusion Shuxuetong injection combined with edaravone injection is better than edaravone injection to treat acute cerebral infarction.