AIM To prepare curcumin-loaded poly (D,L-lactide-co-glycolide) acid (PLGA) nanoparticles,and to investigate their effects on promoting wound healing.METHODS Phacoemulsification method was adopted in the preparation of PLGA nanoparticles.With lactic acid-glycolic acid ratio,surfactant type and concentration and PLGA consumption as influencing factors,encapsulation efficiency,drug loading,particle size and PDI as evaluation indices,the preparation process was optimized by single factor test.The morphology was observed under transmission electron microscopy,after which the in vitro drug release was determined by dialysis bag method,the optical properties were investigated by fluorescence spectroscopy,and the effects on promoting wound healing of mouse skin.RESULTS The optimal conditions were determined to be 50∶50 for lactic acid-glycolic acid ratio,60 mg for PLGA consumption,and 3％ for surfactant (PVA) concentration.The obtained PLGA nanoparticles with spherical core-shell structure demonstrated the average particle size,PDI,Zeta potential and accumulative release rate within 168 h of (149.70±7.27) nm,0.28±0.04 and (-10.18±1.00) mV and (39.21±1.44)％,respectively,which displayed typical aggregation-induced emission property,excitation wavelength-dependent property and optical stability.Compared with the PBS group,PBS+illumination group,curcumin+illumination group and preparation group,the preparation+illumination group exhibited increased wound healing rate (P<0.05,P<0.01) and reduced wound epidermal thickness (P<0.05,P<0.01).CONCLUSION Curcumin-loaded PLGA nanoparticles show good optical properties,which can promote the wound healing of mouse skin when combined with photodynamic therapy.

AIM To prepare curcumin-loaded poly (D,L-lactide-co-glycolide) acid (PLGA) nanoparticles,and to investigate their effects on promoting wound healing.METHODS Phacoemulsification method was adopted in the preparation of PLGA nanoparticles.With lactic acid-glycolic acid ratio,surfactant type and concentration and PLGA consumption as influencing factors,encapsulation efficiency,drug loading,particle size and PDI as evaluation indices,the preparation process was optimized by single factor test.The morphology was observed under transmission electron microscopy,after which the in vitro drug release was determined by dialysis bag method,the optical properties were investigated by fluorescence spectroscopy,and the effects on promoting wound healing of mouse skin.RESULTS The optimal conditions were determined to be 50∶50 for lactic acid-glycolic acid ratio,60 mg for PLGA consumption,and 3％ for surfactant (PVA) concentration.The obtained PLGA nanoparticles with spherical core-shell structure demonstrated the average particle size,PDI,Zeta potential and accumulative release rate within 168 h of (149.70±7.27) nm,0.28±0.04 and (-10.18±1.00) mV and (39.21±1.44)％,respectively,which displayed typical aggregation-induced emission property,excitation wavelength-dependent property and optical stability.Compared with the PBS group,PBS+illumination group,curcumin+illumination group and preparation group,the preparation+illumination group exhibited increased wound healing rate (P<0.05,P<0.01) and reduced wound epidermal thickness (P<0.05,P<0.01).CONCLUSION Curcumin-loaded PLGA nanoparticles show good optical properties,which can promote the wound healing of mouse skin when combined with photodynamic therapy.

OBJECTIVE: To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML). METHODS: The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m² /d×3 d). RESULTS: Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019). CONCLUSION Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.
Male ; Female ; Humans ; Decitabine ; Retrospective Studies ; Transplantation, Homologous/adverse effects* ; Transplantation Conditioning/adverse effects* ; Myelodysplastic Syndromes/complications* ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Chronic Disease ; Graft vs Host Disease/therapy* ; Recurrence

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

OBJECTIVES: To study the expression level of plasma miR-106b-5p in primary immune thrombocytopenia (ITP) and its correlation with the levels of T helper 17 cell (Th17) and regulatory T cell (Treg) and the Th17/Treg ratio. METHODS: A total of 79 children with ITP (ITP group) and 40 healthy children (control group) were selected as subjects. According to the treatment response, the 79 children with ITP were divided into three groups: complete response (n=40), partial response (n=18), and non-response (n=21). Quantitative real-time PCR was used to measure the expression level of miR-106b-5p. Flow cytometry was used to measure the frequencies of Th17 and Treg, and the Th17/Treg ratio was calculated. The correlation of the expression level of plasma miR-106b-5p with the frequencies of Th17 and Treg and the Th17/Treg ratio was analyzed. RESULTS: Compared with the control group, the ITP group had significantly higher levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significantly lower level of Treg (P<0.05). After treatment, the ITP group had significant reductions in the levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significant increase in the level of Treg (P<0.05). Compared with the partial response and non-response groups, the complete response group had significantly lower levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significantly higher level of Treg (P<0.05). The correlation analysis showed that in the children with ITP, the expression level of plasma miR-106b-5p was positively correlated with the Th17 level and the Th17/Treg ratio (r=0.730 and 0.816 respectively; P<0.001) and was negatively correlated with the Treg level (r=-0.774, P<0.001). CONCLUSIONS A higher expression level of miR-106b-5p and Th17/Treg imbalance may be observed in children with ITP. The measurement of miR-106b-5p, Th17, Treg, and Th17/Treg ratio during treatment may be useful to the evaluation of treatment outcome in children with ITP.
Child ; Humans ; Lymphocyte Count ; MicroRNAs/genetics* ; Purpura, Thrombocytopenic, Idiopathic/genetics* ; T-Lymphocytes, Regulatory ; Th17 Cells

Objective: Patients with opioid use disorder (OUD) have impaired attention, inhibition control, and memory function. The aldehyde dehydrogenase 2 (ALDH2 ) gene has been associated with OUD and ALDH2 gene polymorphisms may affect aldehyde metabolism and cognitive function in other substance use disorder. Therefore, we aimed to investigate whether ALDH2 genotypes have significant effects on neuropsychological functions in OUD patients undergoing methadone maintenance therapy (MMT). Methods: OUD patients undergoing MMT were investigated and followed-up for 12 weeks. ALDH2 gene polymorphisms were genotyped. Connors’ Continuous Performance Test (CPT) and the Wechsler Memory Scale-Revised (WMS-R) were administered at baseline and after 12 weeks of MMT. Multivariate linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the ALDH2 genotypes and performance on the CPTs and WMS-R. Results: We enrolled 86 patients at baseline; 61 patients completed the end-of-study assessments. The GEE analysis showed that, after the 12 weeks of MMT, OUD patients with the ALDH2 *1/*2＋*2/*2 (ALDH2 inactive) genotypes had significantly higher commission error T-scores (p = 0.03), significantly lower hit reaction time T-scores (p = 0.04), and significantly lower WMS-R visual memory index scores (p = 0.03) than did patients with the ALDH2 1 */*1 (ALDH2 active) genotype. Conclusion OUD patients with the ALDH2 inactive genotypes performed worse in cognitive domains of attention, impulse control, and memory than did those with the ALDH2 active genotype. We conclude that the ALDH2 gene is important in OUD and is associated with neuropsychological performance after MMT.

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.

BACKGROUNDRecrossing the compromised side branch (SB) with a balloon is sometimes technically challenging. The aim of this study was to evaluate whether in-stent anchoring (ISA) is safe and effective to facilitate SB balloon delivery for final kissing.

METHODSOne hundred and fifty-nine consecutive patients were included (166 bifurcation lesions) in this prospective, single-center registry. ISA was used as a bailout method after unsuccessful SB crossing using conventional techniques, including low-profile balloons. Technique success was defined as SB balloon delivery and final kissing.

RESULTSKissing-balloon delivery was successfully performed with conventional strategies in 149 of 166 lesions (89.8%). In the remaining 17 lesions (10.2%), recrossing of the main vessel stent strut was not successful; therefore, ISA was attempted. The balloon successfully crossed the stent struts, and final kissing was achieved in 15 of 17 lesions (88.2%). Total final kissing was achieved in 164 of 166 lesions (98.8%), with success rates of 100% in the single-stent group and 97.6% in the two-stent group. Two cases without balloon delivery had complex bifurcation lesions with severe calcification. There was no vessel dissection in the anchoring zone.

CONCLUSIONSISA is safe and effective for recrossing stent struts when conventional low-profile balloons have failed. However, large-scale trials are warranted for further evaluation.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Angiography ; methods ; Coronary Artery Disease ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Registries ; Treatment Outcome

OBJECTIVETo establish a neonatal pig model of hemolytic jaundice.

METHODSTwelve seven-day-old purebred Yorkshire pigs were randomly divided into an experimental group and a control group (n=6 each). Immunization of New Zealand white rabbits was used to prepare rabbit anti-porcine red blood cell antibodies, and rabbit anti-porcine red blood cell serum was separated. The neonatal pigs in the experimental group were given an intravenous injection of rabbit anti-porcine red blood cell serum (5 mL), and those in the control group were given an intravenous injection of normal saline (5 mL). Venous blood samples were collected every 6 hours for routine blood test and liver function evaluation.

RESULTSThe experimental group had a significantly higher serum bilirubin level than the control group at 18 hours after the injection of rabbit anti-porcine red blood cell serum (64±30 μmol/L vs 20±4 μmol/L; P<0.05). In the experimental group, the serum bilirubin level reached the peak at 48 hours (275±31 μmol/L), and decreased significantly at 96 hours after the injection (95±17 μmol/L), but all significantly higher than that in the control group (P<0.05). At 18 hours after the injection, the experimental group had a significantly lower red blood cell (RBC) count than the control group [(4.58±0.32)×10(12)/L vs (5.09±0.44)×10(12)/L; P<0.05]; at 24 hours, the experimental group showed further reductions in RBC count and hemoglobin level and had significantly lower RBC count and hemoglobin level than the control group [RBC: (4.21±0.24)×10(12)/L vs (5.11±0.39)×10(12)/L, P<0.05; hemoglobin: 87±3 g vs 97±6 g, P<0.05]. The differences in RBC count and hemoglobin level between the two groups were largest at 36-48 hours.

CONCLUSIONSThe neonatal pig model of hemolytic jaundice simulates the pathological process of human hemolytic jaundice well and provides good biological and material bases for further investigation of neonatal hemolysis.

Animals ; Animals, Newborn ; Bilirubin ; blood ; Disease Models, Animal ; Erythrocyte Count ; Female ; Hemoglobins ; analysis ; Jaundice ; etiology ; Male ; Rabbits ; Swine

OBJECTIVETo study the effect of Dangua Recipe (DGR) on glycolipid metabolism, vascular cell adhesion molecule-1 (VCAM-1) and its mRNA expression level of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis, thus revealing its partial mechanism for curing diabetes mellitus (DM) with angiopathy.

METHODSDiabetic model was prepared by peritoneally injecting streptozotocin (STZ) to Apo E(-/-) mouse. Totally 32 modeled mice were stratified by body weight, and then divided into 4 groups referring to blood glucose levels from low to high by random digit table, i.e., the model group (MOD, fed with sterile water, at the daily dose of 15 mL/kg), the DGR group (fed with DGR at the daily dose of 15 mL/kg), the combination group (COM, fed with DGR at the daily dose of 15 mL/kg and pioglitazone at the daily dose of 4.3 mg/kg), and the pioglitazone group (PIO, at the daily dose of 4.3 mg/kg), 8 in each group. Another 8 normal glucose C57 mouse of the same age and strain were recruited as the control group. All interventions lasted for 12 weeks by gastrogavage. The fasting blood glucose (FBG), body weight, food intake, water intake, skin temperature, the length of tail, and the degree of fatty liver were monitored. The hemoglobin A1c (HbA1c), total cholesterol (TC), and LDL-C were determined. Endothelin-1 (ET-1) was determined by radioimmunoassay. Nitrogen monoxidum (NO) was determined by nitrate reductase. The kidney tissue VCAM-1 level was analyzed with ELISA. The expression of VCAM-1 mRNA in the kidney tissue was detected with real time quantitative PCR.

RESULTSCompared with the control group, the body weight and food intake decreased, water intake increased in all the other model groups (P < 0.05). Besides, the curve of blood glucose was higher in all the other model groups than in the control group (P < 0.01). Compared with the model group, the body weight increased; levels of HbAlc, TC, LDL-C, ET-1, and VCAM-1 were significantly lower; and skin temperature was higher in the DGR group (P < 0.05, P < 0.01). Compared with the PIO group, body weight, the increment of body weight, FBG, TC, and LDL-C were lower (P < 0.05, P < 0.01); food intake and water intake increased more and the tail length was longer in the DRG group (P < 0.01). There was no statistical difference in the level of NO among groups. The degree of fatty liver in the model group was significantly severer than that in the control group (P < 0.05). It was obviously alleviated in the DGR group (P < 0.05) when compared with the model group and the PIO group (P < 0.05, P < 0.01). But it was severer in the PIO group than in the model group (P < 0.01). The degree of fatty liver in the combination group ranged between that of the DGR group and the PIO group (P < 0.05). The level of VCAM-1 mRNA expression was significantly lower in the DGR group than in the model group, the PIO group, and the combination group (P < 0.05).

CONCLUSIONSDGR had effect in lowering blood glucose and blood lipids, and fighting against fatty liver of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis. DGR played an effective role in preventing and treating DM with angiopathy by comprehensively regulating glycolipid metabolism and promoting the vascular function.

Animals ; Apolipoproteins E ; genetics ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; Diabetic Angiopathies ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Lipids ; blood ; Male ; Mice ; Mice, Knockout ; RNA, Messenger ; genetics ; Random Allocation ; Thiazolidinediones ; pharmacology ; Vascular Cell Adhesion Molecule-1 ; genetics ; metabolism