Microsphere as a drug delivery system with broad prospect for development and application has always been a research focus in pharmaceutics for its. Though literature survey of related papers published in domestic and foreign journals by Chinese authors in 2016, the research advances of materials of microspheres, which can be divided into natural polymer materials, synthetic polymer materials and inorganic materials, were summarized. Microsphere products at home and abroad were also analyzed. This review will provide some reference for correlative researchers.

In this paper, silymarin nanoemulsions(SM-NE)were prepared based upon PC/Tween 80 system, and adsorption of lactoferrin(LF)absorbed onto the surface of silymarin nanoemulsions via electrostatic interaction resulted in the formation of lactoferrin-modified silybin nanoemulsions(LF-SM-NE). SM-NE and LF-SM-NE were characterized in terms of the shape, diameter, zeta potential, and entrapment efficiency. In addition, in vivo absorption of SM-NE and LF-SM-NE following oral dosing was investigated by the application of LC-MS/MS in the determination of silymarin in blood sample. The results showed that the saturated adsorption of Lf at the surface of the SM-NE occurred at LF concentration of 0. 15 mg/mL and the incubation time of 4 h. LF-SM-NE were spherical with average particle size of(257±5. 9)nm, zeta potential of -(33. 1±1. 5)mV, entrapment efficiency(96. 9±1. 9)% and drug loading(3. 90±0. 12)%. Compared with those of SM-NE, LF-SM-NE significantly increased drug levels of LF in rats were observed after dosing of LF-SM-NE, and both of cmax and AUC were increased by approximately 2-fold. In summary, LF-SM-NE could improve oral drug absorption of LF in rats. The approach of enhancement in oral absorption of the nanoemulsions shows a promise for the application.

PLZ-NPs (PNS-lipid-zein nanoparticles) prepared by co-assembly of Panax notoginseng saponins, lecithin, β-sitosterol and zein were applied for in vitro cell experiment and oral gavage to study the protective effect of cerebral ischemia-reperfusion rats.PLZ-NPs were characterized by Malvin-particle size analyzer and transmission electron microscope (TEM), respectively. The toxicity of PLZ-NPs and free carrier were evaluated by MTT, and the uptake of nanoparticles in Caco-2 cells was analyzed by laser confocal and flow cytometry. The cerebral ischemia reperfusion rat model was established by MCAO method and then be given samples by gavage for 3 days. The brain tissues were taken to stain by 2, 3, 5-triphenyltetrazole chloride (TTC) and the biochemical indicators of MDA, inflammatory cytokines IL-1β and TNF-α, apoptosis-related proteins Bax and Bcl-2 from the harvested brain tissues were detected to evaluate the protective effect of PNS in PLZ-NPs on cerebral ischemia reperfusion. The particle size, PDI, and zeta potential of formed PLZ-NPs were (116.4 ± 0.81) nm, 0.048 and -(31.5 ± 0.31) mV, respectively. The results of MTT showed that the zein lipoprotein carrier was non-toxic to Caco-2 cells. The results of laser confocal and flow cytometry showed that FITC uptake of nanoparticles could be significantly improved in Caco-2 cells.The uptake from the nanoparticles at 4h was 1.76 times of that of the free FITC group.Compared with the model group, the TTC staining images of free drug PNS group and PLZ-NPs group showed certain reduction in the white infarct area.The contents of MDA, IL-1β, TNF-α and Bax were significantly decreased, while the content of Bcl-2 was significantly increased. Furthermore, all parameters of PLZ-NPs group showed better results than those of PNS group, and there was a significant difference (P < 0.05). All results indicated that the prepared PLZ-NPs had good stability and biological safety, and could significantly increase the uptake in intestinal epithelial cells, and effectively protect against the damage caused by cerebral ischemia reperfusion in rats.

Objective To investigate the characteristics and failure risk factors of sequential high-flow nasal cannula oxygen therapy (HFNC) after weaning from invasive ventilation. Methods The patients who received sequential HFNC after weaning from invasive ventilation admitted to surgical intensive care unit (ICU) of Peking University People's Hospital from June 1st 2016 to May 31st 2018 were retrospectively analyzed. Clinical variables, respiratory therapy parameters, respiratory variables, cardiac variables and outcomes were reviewed and analyzed. Treatment characteristics of HFNC after weaning was analyzed. Patients were divided into HFNC success group and HFNC failure group according to the failure of HFNC, and the differences between the two groups were compared. The independent risk factors of HFNC treatment failure were analyzed by Logistic regression analysis. The value of predictive treatment failure of risk factors and regression models were analyzed by receiver operating characteristic (ROC) curve. Results A total of 99 patients were included, 61 men, and the median age was 67.0 (57.0, 76.0) years old. The medianinitial HFNC flow was 50 (50, 60) L/min, and inspired oxygen concentration (FiO2) was 0.50 (0.40, 0.60). Eighteen patients experienced HFNC failure (18.2%). Compared with the HFNC success group, the sequential organ failure assessment (SOFA) score in the HFNC failure group was higher [4 (3, 5) vs. 2 (1, 3), P < 0.01], B type natriuretic peptide (BNP) before HFNC therapy were significant higher [ng/L: 647.2 (399.2, 1 331.3) vs. 127.2 (55.2, 369.5), P < 0.01], and respiratory frequency (RR) and heart rate (HR) were significant faster, mean arterial pressure (MAP) was significant higher, oxygen index (PaO2/FiO2) was significant lower after 30 minutes HFNC treatment [RR (times/min): 26 (22, 28) vs. 19 (17, 21), HR (bpm): 105 (97, 107) vs. 85 (77, 90), MAP (mmHg, 1 mmHg = 0.133 kPa): 104.3 (101.7, 110.7) vs. 92.3 (88.3, 97.7), PaO2/FiO2 (mmHg): 207.3 (185.8, 402.8) vs. 320.2 (226.2, 361.5), all P < 0.05]. It was shown by multiple Logistic regression analysis that the SOFA score [odds ratio (OR) = 2.818, P = 0.022, β = 1.036], BNP before HFNC treatment (OR = 1.002, P = 0.033, β = 0.002) and HR after HFNC treatment 30 minutes (OR = 1.140, P = 0.032, β = 0.131) were independent risk factors for HFNC treatment failure. It was shown by ROC curve that the area under the ROC curve (AUC) for the prediction of HFNC failure was 0.840, 0.859, 0.860 and 0.962 for SOFA, BNP before HFNC treatment, HR after HFNC treatment 30 minutes, and regression model, all had good forecast values (all P < 0.01). Conclusions HFNC is one of the commonly used oxygen therapy methods in the ICU, but not all patients who are treated as a sequential therapy after invasive mechanical ventilation weaning can benefit from it. SOFA score, BNP before HFNC treatment and HR after 30 minutes HFNC treatment were independent risk factors of HFNC failure. Each independent risk factor and regression model can predict the success of HFNC treatment.

Objective To observe the impact of adaptive statistical iterative reconstruction-V (ASiR-V) on image quality and radiation dose in abdominal CT imaging,and to optimize combination of pre-and post ASiR-V percentage.Methods Totally 160 patients underwent plain and contrast-enhanced abdominal CT were randomly divided into study group or control group (each n=80).In study group,plain images were reconstructed with 20％ pre ASiR-V combined with 20％,40％,60％ and 80％ post-ASiR-V,the arterial phase images were reconstructed with 40％ pre-ASiR V combined with 40％,60％ and 80％ post-ASiR-V,while the venous phase images with 60％ pre-ASiR-V combined with 60％ and 80％ post-ASiR-V,and the delayed phase images with 80％ pre-ASiR-V combined 80％ post-ASiR-V.In control group,images were reconstructed with filtered back projection (FBP) and 0 pre-ASiR-V combined post-ASiR-V (20％ in plain,40％ in arterial phase,60％ in venous phase and 80％ in delayed phase imaing).The objective parameters (image noise [SD] and CNR) and image quality scores were analyzed and compared.Results CT dose index,dose length product and effective dose of each phase in study group were lower than those in control group (all P＜0.001).In study group,with the increasing of post-ASiR-V percentage,SD values gradually decreased (P＜0.01),and CNR gradually increased or did not change.With the increasing of post-ASiR-V (20％-60％),image quality scores increased,and image quality of 80 ％ post-ASiR-V was low.In study group,image quality of 20％ pre-ASiR-V combined 40％ or 60％ post-ASiR-V was similar to 20％ post-ASiR-V image in control group in plain,and that of 40％ pre-ASiR-V combined 60％ post-ASiR-V was similar to 40％ post-ASiR-V image in control group in arterial phase (all P＞0.05),while image quality scores of other combinations of pre-and post-ASiR-V percentages were lower than those in control group.Conclusion ASiR-V can improve abdominal CT image quality,and 40％ pre-ASiR-V combined 60％ post-ASiR V is recommended.

Objective To investigate the value of wide-detector helical CT combined with adaptive statistical iterative reconstruction-V (ASIR-V) in the low radiation dose CT examination of upper abdomen in obese patients.Methods In the first phantom experiment part,the optimal percentage of pre-and post-ASIR-V of abdominal scanning (120 kVp,NI =10 HU) were explored.The second human experiment was performed based on the phantom study,and our institutional review board approved this prospective study,each participant provided written informed consent.87 obese patients (body mass index,BMI ≥30 kg/m2) underwent contrast-enhanced abdominal CT scan were randomly divided into two scan protocols [protocol A:n =43,120 kVp,detector coverage of 80 mm,40％ pre-ASIR-V (group A1)and combined with 60％ post-ASIR-V (group A2) respectively;protocol B,n =44,120 kVp,detector coverage of 40 mm,40％ ASIR (group B)].Quantitative parameters [image noise and contrast-to-noise ratio (CNR)] and qualitative visual parameters (overall image quality as graded on a 5-point scale) were compared.Weighted effective dose (E) were assessed.Results The optimal percentage of pre-and post-ASIR-V of abdominal scanning were 40％ and 60％,respectively.The effective radiation dose in protocol A [(4.55 ± 0.95) mSv] was decreased for 53％ as compared with protocol B [(9.58 ± 2.04) mSv](t =-14.773,P ＜ 0.001).During the arterial phase and portal venous phase,except for the CNRs of liver,Group A2 showed higher CNRs (q =2.160-3.209,P ＜ 0.05),lower image noise(q =-4.212--3.202,P＜0.05),and higher overall image quality scores(Z =-5.155--2.561,P ＜0.05) as compared with group A1 and group B.Group A1 showed similar CNRs,similar image noise(P ＞ 0.05),and lower overall image quality scores (Z =-3.298--3.030,P ＜ 0.05) than group B.The overall image quality scores in group A were all greater than 3 point and met the clinical diagnostic level.Conclusions Compared with stand-detector helical CT in obese patients,the wide-detector helical CT combined with 40％ pre-ASIR-V could reduce the radiation dose by 53％,and improve overall image quality by combining post-ASIR-V technique.

The surface solid dispersion of honokiol was prepared by melting method with croscarmellose sodium as carrier to improve the dissolution rate of honokiol, taking the advantage of its low melting point. The dissolution rate and stability test of surface solid dispersion of honokiol were carried out. Its physical properties were then investigated by DSC, PXRD and SEM analysis. The results indicated that the dissolution rate of honokiol from sodium solid dispersion was more than 90% at 15 min while its mean dissolution time was significantly decreased. Honokiol was distributed on the surface of croscarmellose sodium in the form of microcrystal; moreover, its dissolution behavior didn′t change significantly after six months of stability tests. Therefore, surface solid dispersion of honokionl could be prepared by simple process. The formed solid dispersion achieved high drug loading and fast in vitro dissolution rate, which could provide a novel idea for developing solid preparations of honokiol.

This paper aimed at studying the effects of hyaluronic acid (HA) with different molecular weights on the transdermal absorption and retention of reduced glutathione (GSH) in the isolated skin of SD rats. Franz diffusion cell method was used to investigate the effects with different molecular weights HA on the in vitro transdermal penetration of GSH and the storage in different layers of the skin. AutoDock molecular docking was used to study the interaction between GSH and HA. Attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR) and H&E section staining were used to characterize the changes and effects of lipids and proteins in the rat stratum corneum after HA acts on the skin. The results of in vitro transdermal experiments showed that HA with different molecular weights had a significant impact on the amount of GSH passing through the skin, that as the molecular weight of HA increased, the effect of preventing GSH from passing through the skin became stronger, that in terms of skin storage, HA with different molecular weights could increase the storage of GSH in the stratum corneum, and that HA with a molecular weight below 7K could also significantly increase the storage of GSH in the dermis. The molecular docking results showed that HA and GSH had a relatively strong interaction, which could form intermolecular hydrogen bonds; and the results of ATR-FTIR and H&E staining showed that HA could interact with lipids and keratins in the stratum corneum of the skin. Such interaction can increase the permeability of the stratum corneum of the drug, however, as a water-soluble GSH, it may be involved in the formation of intermolecular hydrogen bonds with HA. In the structure of HA hydrogel, the amount of GSH drug passing through the intact skin is reduced; but at the same time, this interaction also provides a reservoir for the formation of GSH, thus increasing its storage in the skin. Through comparison of the storage capacity of GSH in the stratum corneum and dermis of the isolated skin due to the increase of HA with different molecular weights, it has been found that the storage capacity of HA with low relative molecular weight is the best.

Objective:To investigate the efficiency of deep learning image reconstruction (DLIR) algorithm in the image quality and detection of hypovascular hepatic metastases under low radiation doses in comparison with adaptive statistical iterative construction-V (ASiR-V).Methods:Fifty-six patients with suspected hypovascular hepatic metastases who needed abdominal enhanced CT scans were collected prospectively in the First Affiliated Hospital of Zhengzhou University from January to April 2021. The patients received conventional radiation dose with tube current-time products of 400 mA CT scans in the first venous phase, low-dose CT scans in the second venous phase, which were set as tube current-time products of 280 mA for group A (19 cases), 200 mA for group B (19 cases) and 120 mA for group C (18 case), respectively. The images of first venous phase and 3 groups of second venous phase were both reconstructed with ASiR-V60% and high-DLIR (DLIR-H). Quantitative parameters [image noise, liver and portal vein signal to noise ratio (SNR), contrast to noise ratio (CNR)] and qualitative parameters (overall image quality, lesion conspicuity, diagnostic confidence) were compared between ASiR-V60% and DLIR-H images, and the effective radiation dose (ED) and the lesion detectability of each group was recorded. The paired t test was used to compare quantitative parameters, whereas the Wilcoxon signed-rank test of paired data was used to compare qualitative parameters. Results:In the second venous phase, ED was (5.56±0.35) mSv in group A, (3.88±0.23) mSv in group B, and (2.42±0.23) mSv in group C, with a decrease of 30%, 50% and 70% compared with the first venous phase, respectively. Moreover, with the decrease of radiation dose, the noise gradually increased, and the CNR lesions, SNR liver and SNR portal vein all gradually decreased. DLIR-H images had statistically better quantitative scores than ASiR-V60% images when the same radiation dose was applied (all P<0.001). Furthermore, the qualitative parameters of each group decreased with the decrease of radiation dose. Under the same radiation dose, the overall image quality, lesion conspicuity and diagnostic confidence of DLIR-H were higher than those of ASiR-V60% (all P<0.001). All lesions [100% (84/84)] were detected by ASIR-V60% and DLIR-H in group A, 92.0% (75/81) in group B, and 88.0% (79/89) in group C. Conclusions:Compared with ASiR-V60%, DLIR-H could reduce image noise, improve overall image quality and lesion conspicuity of hypovascular hepatic metastases as well as increase diagnostic confidence under different radiation doses.

Objective:To evaluate the mid-term complication rates of the Hui-Jing one-stage procedure (lingual mucosa combined with longitudinal preputial island flap onlay urethroplasty + tubularized incised plate glansplasty)versus the classic Bracka staged surgery for children with severe hypospadias.Methods:A retrospective analysis was conducted on clinical data of 75 children with proximal hypospadias who were treated at the Seventh Medical Center of PLA General Hospital from March 2017 to June 2022. Of these patients, 31 cases (15 cases penoscrotal type and 16 cases perineal type) were underwent the Bracka two-stage surgery with a median age of 38 months (24.0, 44.5) and 44 cases underwent the Hui-Jing one-stage procedure (23 cases penoscrotal type and 21 perineal type) with a median age of 40.5 months (20.75, 90.5). The length of urethral plate defect after correction of penile curvature was (4.30±0.84)cm in the Bracka group and (4.56±0.79)cm in the Hui-Jing group, which also showed no significant difference.There was no statistically significant difference of the median age and the position of preoperative urethral opening between the two groups( P=0.47, P=0.74). The first stage of Bracka repair consists of orthoplasty and urethral bed substitution with free preputial graft. After 6 months, the urethral plate created from free graft was tabularized to form neourethra; Hui-Jing procedure group used the free lingual mucosal as urethral plate substitution, then we conducted longitudinal preputial island flap Onlay and Snodgrass phalloplasty. The incidence of postoperative urethral fistula, urethral stricture and urethral diverticulum was compared between the two groups of cases and the difference in efficacy between the two procedures was assessed. Results:Among the 75 patients included in the study, there was no statistically significant difference in age or location of urethral meatus between the Bracka and Hui-Jing groups. In Bracka group, 9 cases of urethral stricture (29.0%), 6 case of urethral fistula (19.4%), and 2 cases of urethral diverticulum (6.5%) occurred after surgery, while 12 cases of urethral fistula (27.3%) and 3 case of urethral fistula (6.8%) occurred in the Hui-Jing group. No urethral stricture occurred in Hui-Jing group. There was no statistically significant difference in overall incidence of complications between the two groups [17/31(54.8%) vs.15/44(34.1%), P=0.12]. The incidence of urethral fistula and urethral diverticulum show no significant differences between two groups(19.4% vs 27.3, P=0.61, 6.5% vs. 6.8%, P=0.13). The number of operation in Bracka group was (2.68±1.03) and the hospitalization cost was (12 984.63±3 808.15) Yuan, while the number of operation in Hui-Jing group was (1.36±0.53) and the hospitalization cost was (8 490.54±3 136.84) Yuan. Conclusions:The Hui-Jing one-stage procedure can be used for the surgical treatment of children with severe hypospadias. There is no urethral stricture happened in Hui-Jing group, while the general complication incidence and incidence of urethral fistula and diverticulum show no differences.