Objective To study the bioequivalence and safety of two olmesartan medoxomil and hydrochlorothiazide tablets in Chinese healthy subjects.Methods A total of 24 healthy subjects underwent fasting and postprandial tests in a single-center,randomized,open-label,single-dose,two-formulation,two-sequence,two-period,self-cross-over controlled design.The subjects were administered a single oral dose of the test formulation and reference formulation(each containingolmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg)in a random cross-over fashion.The plasma concentrations of olmesartan and hydrochlorothiazide were determined by LC-MS/MS.The non-compartmental model analysis of olmesartan and hydrochlorothiazide was conducted using WinNonlin 7.0 software to calculate pharmacokinetic parameters and assess bioequivalence.Results In the fasting test,the pharmacokinetic parameters of olmesartan of test and reference were as follows:Cmax were(798.35±206.78)and(664.52±168.25)ng·mL-1,AUC0-t were(4 430.71±1 294.87)and(3 976.67±1 083.54)h·ng·mL-1,AUC0-∞ were(4 551.67±1 303.06)and(4 090.37±1 103.97)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(92.39±35.96)and(96.15±38.76)ng·mL-1,AUC0_t were(548.69±217.11)and(564.41±208.68)h·ng·mL-1,AUC0-∞ were(603.04±228.59)and(619.26±223.27)h·ng·mL-1.In the fed test,the pharmacokinetic parameters of olmesartan of T and R were as follows:Cmax were(583.15±149.48)and(550.57±104.76)ng·mL-1,AUC0-t were(3 585.18±952.72)and(3 292.19±904.58)h·ng·mL-1,AUC0-∞ were(3 696.05±996.55)and(3 396.30±923.41)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(70.30±17.88)and(74.70±21.65)ng·mL-1,AUC0-t were(476.60±119.39)and(492.91±144.81)h·ng·mL-1,AUC0-∞ were(523.37±132.67)and(535.81±151.92)h·ng·mL-1.In fasting and fed condition,the 90％confidence interval(90％CI)of Cmax,AUC0-t and AUC0-∞ of olmesartan and hydrochlorothiazide were in 80.00％-125.00％.Conclusion The two olmesartan medoxomil and hydrochlorothiazide tablets were bioequivalent under fasting and fed conditions,and good security.

Cancer seriously threatens human life and health, it is urgent for the development of rapid detection, precise localization and effective treatment of tumors. Chemical fluorescent probes that are sensitive to tumor-specific microenvironments have important significance in tumor theranostics and a variety of such probes have been developed. In this review, we classified chemical fluorescent probes that are sensitive to tumor microenvironments according to biological characteristics and microenvironmental changes while combining spectroscopy or response mechanisms, and systematically introduced the research progress of chemical fluorescent probes with sensitivity to hypoxia, low polarity, high viscosity, abnormal pH values and abundant reactive oxygen species in tumor microenvironments, in order to provide references for the development and applications of these probes.

Objective    To evaluate the safety and efficacy of peripheral cannulation for cardiopulmonary bypass (CPB) in patients with reoperation of congenital heart disease. Methods    The perioperative data of patients with congenital heart disease who underwent reoperation in Fuwai Hospital from 2019 to 2020 were retrospectively collected. They were divided into two groups according to the cannulation methods: a central group and a peripheral group. The prognosis of the patients was analyzed. Results     A total of 80 patients were collected, including 43 patients in the central group, and 37 pateints in the peripheral group. In the central group, the median age was 18 (14, 32) years, and 21 patients were male. The median age of the peripheral group was 16 (10, 27 ) years, and 18 patients were male. The CPB time in the peripheral group was 201 (164, 230) min, which was longer than that in the central group [143 (97, 188 ) min, P<0.001]. The lactate after CPB in the peripheral group was statistically higher than that in the central group [2 (1, 2 ) mmol/L vs. 1 (1, 1) mmol/L, P=0.002]. The dosage of albumin use during CPB in the peripheral group was statistically higher than that in the central group [10 (0, 20) g vs. 0 (0, 0) g, P=0.004]. There was no statistical difference in the postoperative dosage of red blood cells use [0 (0, 2) U vs. 0 (0, 0) U, P=0.117], mechanical ventilation time [14 (11, 19) h vs. 13 (10, 15) h, P=0.296], ICU stay time [43 (23, 80) h vs. 40 (20, 67) h, P=0.237] or postoperative hospital stay time [10 (7, 12) d vs. 8 (7, 10) d, P=778] between the two groups. Conclusion    It’s safe and efficient to establish CPB through peripheral cannulation in patients with complex congenital heart disease undergoing reoperation.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Purpose: Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC. Materials and Methods: Three hundred fifty-three patients with resectable PC and 807 patients with locally advan-ced or metastatic PC were recruited in this study. These patients were classified into a training set (n=758) and a validation set (n=402). Kaplan-Meier survival plots and Cox proportional hazards regression models were used to analyze prognosis. Results: Overall survival (OS) was significantly better for patients with resectable PC with low preoperative PLR (p=0.048) and MLR (p=0.027). Low FAR, MLR, NLR (p < 0.001), and PLR (p=0.003) were significantly associated with decreased risk of death for locally advanced or metastatic PC patients. FAR (hazard ratio [HR], 1.522; 95% confidential interval [CI], 1.261 to 1.837; p < 0.001) and MLR (HR, 1.248; 95% CI, 1.017 to 1.532; p=0.034) were independent prognostic factors for locally advanced or metastatic PC. Conclusion The prognostic roles of FAR, MLR, NLR, and PLR in resectable PC and locally advanced or metastatic PC were different. FAR showed the most prognostic power in locally advanced or metastatic PC. Low FAR was positively correlated with OS in locally advanced or metastatic PC, which could be used to predict the prognosis.

Eleven flavonoids were isolated from the twigs of Broussonetia papyrifera by column chromatography over silica gel,ODS,MCI gel,and Sephadex LH-20,as well as RP-HPLC.Their structures were identified by spectroscopic methods including NMR,MS,UV,and IR as broupapyrin A(1),5,7,3',4'-tetrahydroxy-3-methoxy-8-geranylflavone(2),8-prenylquercetin-3-methyl ether(3),broussonol D(4),broussoflavonol B(5),uralenol(6),broussonol E(7),8-(1,1-dimethylallyl)-5'-(3-methylbut-2-enyl)-3',4',5,7-tetrahydroxyflanvonol(8),broussoflavonol E(9),4,2',4'-trihydroxychalcone(10),and butein(11).Compound 1 is a new isoprenylated flavonol.Compounds 3,6,10,and 11 were obtained from the genus Broussonetia for the first time,and 4 and 7 were firstly discovered in B.papyrifera.Compounds 1-5 and 7-9 showed significant inhibitory effects on PTP1 B with IC50 values ranging from(0.83±0.30) to(4.66±0.83) μmol·L-1.
Broussonetia ; chemistry ; Chromatography, High Pressure Liquid ; Flavonoids ; isolation & purification ; pharmacology ; Magnetic Resonance Spectroscopy ; Phytochemicals ; isolation & purification ; pharmacology ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; antagonists & inhibitors

OBJECTIVETo investigate the relationship between NK cell count/activity and acute graft-versus-host disease (aGVHD) in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSA total of 26 patients who had undergone allo-HSCT from January to July 2015 were enrolled in this study. The NK cell count/activity in the peripheral blood of recipients on day 30 after allo-HSCT were monitored by using 4-color flow cytometry. The incidence of aGVHD in patients was evaluated by clinical manifestation combinating with related pathologic indicators, and the relationship between NK cell count/activity and aGVHD were analyzed.

RESULTSIn the aGVHD group and the no-aGVHD group, the NK cell count and activity on days 30 after allo-HSCT were 655±216 cells/µl vs 1169±372 cells/µl(P=0.002) and 7.3±3.6% vs 9.0±3.6% (P=0.008). In the II-IV grade aGVHD group and the 0-I grade aGVHD group, the NK cell count/activity were 617±220 cells/µl vs 1081±399 cells/µl (P=0.001) and 4.2±1.7% vs 8.3±3.5%(P=0.001). As compared with the 0-I grade aGVHD group, patients in the II-IV grade aGVHD group had higher relapse rate (57% vs 5%)(P=0.010) , lower 1-year progression-free survival(PFS) rate (43% vs 84%)(P=0.010).

CONCLUSIONNK cell count/activity on day 30 after allo-HSCT were closely relates with aGVHD, which may be a potential marker for aGVHD and can provide a new target for aGVHD therapy.

OBJECTIVETo compare the therapeutic efficacy of patients with neonatal ABO hemolytic disease treated with introvenous immunoglobin G (IVIG) by different modes of administration.

METHODSNinety-three in patients with neonatal ABO hemolytic disease treated in our hospital were divided into group A (31 cases), B(31 cases) and C (31 cases). Based on basic treatment, the patients in group A were treated by a single high dose of IVIG (1 g/kg), patients in group B were treated by multiple low-dose of IVIG (0.5 g/kg), and the patients in group C treated by placebo without IVIG used as controls. The phototherapy time, jaundice time in 3 groups were observed; the total bilirubin levels in 3 groups were compared before and after treatment; the incidence of anemia, the rate of blood transfusion and the occurrence of bilirubin encephalopathy were compared after treatment between 3 groups.

RESULTSThe phototherapy time, jaundice time in group A were statistically significantly shorter than those in the group B and C (P<0.05), but there was not statistical significantly difference between group B and C(P>0.05). Before treatment, serum TBIL level in 3 groups was not significantly different (P>0.05); and after treatment for 24 h and 48 h, the serum TBIL levels in group A were significantly lower than that in group B and C (P<0.05); after treatment for 72 h, the serum TBIL level in group A was all lower than 34.2 µmol/L; before treatment, Hb levels in 3 groups were not significantly different (P>0.05); Hb level in group A was significantly higher than that in group B and C after treatment for 24 h, 48 h and 72 h (P<0.05). The incidence of anemia in group A after treatment was significantly lower than that in group B and C, and that in group B significantly lower than that in group C(P<0.05). The rate of blood transfusion in group A was significantly lower than that in the group B and C (P<0.05); the rate of blood transfusion was not statistically significantly different between group B and C(P>0.05).

CONCLUSIONThe single high dose of IVIG infusion can effectively reduce the serum TBIL level, shorten treatment time and reduce the incidence of anemia and blood transfusion, so the therapeutic efficacy is significantly improved.

OBJECTIVETo evaluate the relationship between T lymphocyte subsets and the incidence of graft-versus-host disease (GVHD) and its clinical significance of monitoring the changes of T lymphocyte subsets dynamicly on 1, 3, 6, 12 month after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSTwenty cases received allo-HSCT in Department of Hematology of General Hospital of Beijing Military Command from January 2013 to January 2014, including 10 males and 10 females with average age of 20.3 years (3-46 years old), among them 4 cases rectived HLA matched transplantation and 16 cases rectived HLA mismatched transplantation. The levels of T lymphocyte subsets including CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), CD4(+)CD25(high) FOXP3(+) in the peripheral blood were manitored with flow cytometry (FCM) on +1, +3, +6, +12 month after transplantation dynamicly.

RESULTS(1) Follow up to March 2015, the levers of CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), CD4(+) CD25(high) FOXP3(+) showed a different degree of recovery after transplantation for all cases and returned to the lever of pre-transplantation on 12 month basically, and CD8(+) T cells recovered earlier than CD4(+) T cells, while the decrease of CD4(+) T cells lasted more than 1 year; The proportion inversion of CD4(+)/CD8(+) also lasted for more than 1 year;(2) The level of CD4(+) CD25(high) FOXP3(+) in patients with acute GVHD was lower than that in patients without acute GVHD.

CONCLUSIONThe dynamic monitoring of the T lymphocyte subsets, especially CD4(+) CD25(high) FOXP3(+) after transplantation has importent clinical significance, it can forecast the incidence of acute GVHD before symptoms appeared; the dynamic monitoring of the T-lymphocyte subsets also can be used as reference indicator for prediction of GVHD, theraby it can reduce mortality of patients after transplantation.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Flow Cytometry ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; T-Lymphocyte Subsets ; cytology ; Young Adult

Objective To explore the clinical significance of the relationship between the immune function and the pathogenesis of aplastic anemia in children with aplastic anemia(AA),along with the incidence of graft versus host disease (GVHD)by monitoring the changes of T lymphocyte subsets dynamically in +1 ,+3,+6,+1 2 months for blood disease patients after allogeneic hematopoietic stem cell transplantation.Methods Twelve AA patients re-ceived allogeneic hematopoietic stem cell transplantation in Department of Hematology,the Affiliated General Hospital of Beijing Military Region of Anhui Medical University,from January 201 3 to January 201 4,including 4 male and 8 fe-male,with average age of 7.92 years old(3 -1 4 years old)with 5 cases of human leukocyte antigen(HLA)matched and 7 cases of HLA mismatched.The level of T lymphocyte subsets including CD3 +,CD4 +,CD8 +,CD4 +/CD8 +, CD56 +,CD4 +CD25 high +FOXP3 +were monitored with flow cytometry before transplantation and in +1 ,+3,+6,+1 2 months after transplantation dynamically in the peripheral blood.While in the same period the level of T lymphocyte subsets was monitored in 1 2 cases of healthy children at the same period as the healthy control group.Results Fol-lowed up to March 201 5,1 0 cases had abnormal cellular immunity (CD4 +/CD8 + ratio inversion)in the 1 2 AA pa-tients.Compared with the control group,in the AA group,CD3 + was slightly higher,(66.79 ±7.35)% and (62.74 ± 5.58)% respectively(P =0.043),CD4 + was decreased by (33.73 ±7.26)% and (39.54 ±3.46)% respectively (P =0.037),CD8 + was increased by (35.69 ±6.78)% and (25.34 ±4.36)%,respectively (P =0.000),CD4 +/CD8 + decreased by 1 .23 ±0.56 and 1 .78 ±0.34 respectively(P =0.001 )and CD56 + was decreased by (7.46 ± 2.80)% and (1 6.73 ±3.70)% respectively(P =0.000),CD4 +CD25 high +FOXP3 + was decreased by (3.3 ± 1 .5)% and (8.1 ±1 .3)% respectively (P =0.003),whose difference was statistically significant (P <0.05).The lever of CD3 +,CD4 +,CD8 +,CD4 +/CD8 +,CD56 +,CD4 +CD25 high +FOXP3 + had a different degree of recovery after transplantation for all cases and returned to normal in +1 2 months basically.In +1 ,+3,+6,+1 2 months after transplantation,the levels of CD4 +CD25 high +FOXP3 + in GVHD positive group and negative group were (0.4 ± 0.6)% and (1 .6 ±0.7)% respectively,(0.7 ±0.3)% and (2.7 ±0.4)% respectively,(1 .1 ±0.5 )% and (2.9 ±0.7)% respectively,(1 .4 ±0.3)% and (3.6 ±0.2)% respectively,which had statistical significance (P <0.05).Conclusions There was abnormal cell immune function in some cases with AA.After transplantation,the level of CD4 +CD25 high +FOXP3 + is closely related to the acute GVHD,which can be used to predict the occurrence of GVHD.