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Additional file 1: Fig. S1. Forest plot of PTA at different time points with the combination therapy compared with traditional therapy. Compared with the traditional therapy group, PTA in the combination therapy group was significantly higher at 12, 24, 36, and 48 weeks (P < 0.05). No significant heterogeneity was observed, and a fixedeffects model was used for statistical analysis. In the plane rectangular coordinate system, the forest plot takes a vertical invalid line (scale of abscissa is 0) as the center, describes the effect quantity and 95% CI of each study by using multiple line segments parallel to the horizontal axis, and describes the effect quantity and confidence interval of multiple studies by using a diamond. PTA, prothrombin time activity; CI, confidence interval; WMD, weighted mean difference. Fig. S2. Forest plot of PT at different time points with the combination therapy compared with traditional therapy. Compared with the traditional therapy group, PT in the combination therapy group was nonsignificantly lower at 1 week (P > 0.05), significantly lower at 2, 4, 12, 24, and 48 weeks (P < 0.05). Since significant heterogeneity was observed in one group (I2 = 87%), a random-effects model was used. In the plane rectangular coordinate system, the forest plot takes a vertical invalid line (scale of abscissa is 0) as the center, describes the effect quantity and 95% CI of each study by using multiple line segments parallel to the horizontal axis, and describes the effect quantity and confidence interval of multiple studies by using a diamond. PT, prothrombin time; CI, confidence interval. WMD, weighted mean difference. Fig. S3. Forest plot of the subgroup analysis of the 6-month clinical performance according to the number of stem cell injection cycles. (A) TBIL; (B) ALB; (C) ALT. The level of TBIL, and ALB in patients who received single-injection of stem cells were significantly different as compared to those in the patients who received two-injections of stem cells (P < 0.05), nonsignificantly difference for the level of ALT (P > 0.05). No significant heterogeneity was observed, and a fixed-effects model was used for statistical analysis. In the plane rectangular coordinate system, the forest plot takes a vertical invalid line (scale of abscissa is 0) as the center, describes the effect quantity and 95% CI of each study by using multiple line segments parallel to the horizontal axis, and describes the effect quantity and confidence interval of multiple studies by using a diamond. TBIL, total bilirubin; ALB, albumin; ALT, alanine aminotransferase; CI, confidence interval; SMD, standardized mean difference. Fig. S4. Forest plot of the subgroup analysis of the 6-month clinical performance according to the number of stem cell injection cycles. (A) AST; (B) CTP; (C) MELD. The level of CTP, and MELD in patients who received single-injection of stem cells were significantly different as compared to those in the patients who received two-injections of stem cells (P < 0.05), nonsignificantly difference for the level of AST (P > 0.05). Since no significant heterogeneity was observed in the figure A and B, a fixed-effect model was used. However, significant heterogeneity was observed in figure C (I2 = 85%), therefore, a random-effects model was used. In the plane rectangular coordinate system, the forest plot takes a vertical invalid line (scale of abscissa is 0) as the center, describes the effect quantity and 95% CI of each study by using multiple line segments parallel to the horizontal axis, and describes the effect quantity and confidence interval of multiple studies by using a diamond. AST, aspartate aminotransferase; CTP, Child-Pugh score; MELD, Model for end-stage liver disease; CI, confidence interval; SMD, standardized mean difference. Fig. S5. Forest plot of the subgroup analysis of the 6-month clinical performance according to the species of adult stem cells. (A) TBIL; (B) ALB. The level of TBIL decreased considerably in the studies transplanting MNCs (P < 0.05), nonsignificantly different in the studies transplanting CD34 + APBSC or ABMMSC (P>0.05). In addition, the level of ALB in patients who received CD34 + APBSC or MNCs were significantly different (P < 0.05), nonsignificantly different in patients who received ABMMSC (P > 0.05). No significant heterogeneity was observed, and a fixed-effects model was used for statistical analysis. In the plane rectangular coordinate system, the forest plot takes a vertical invalid line (scale of abscissa is 0) as the center, describes the effect quantity and 95% CI of each study by using multiple line segments parallel to the horizontal axis, and describes the effect quantity and confidence interval of multiple studies by using a diamond. TBIL, total bilirubin; ALB, albumin; CI, confidence interval; SMD, standardized mean difference. Fig. S6. Forest plot of subgroup analysis. (A) Subgroup analysis of the use of G-CSF in terms of TBIL at twelve weeks. (B) Subgroup analysis of the use of G-CSF in terms of TBIL at twenty-four weeks. (C) Subgroup analysis of the use of G-CSF in terms of ALB at twelve weeks. (D) Subgroup analysis of the use of GCSF in terms of ALB at twenty-four weeks. The level of TBIL at 12, and 24 weeks in patients who received G-CSF mobilized stem cells were nonsignificantly different (P > 0.05). The rest of the subgroups were significantly different (P < 0.05). No significant heterogeneity was observed, and a fixed-effects model was used for statistical analysis. In the plane rectangular coordinate system, the forest plot takes a vertical invalid line (scale of abscissa is 0) as the center, describes the effect quantity and 95% CI of each study by using multiple line segments parallel to the horizontal axis, and describes the effect quantity and confidence interval of multiple studies by using a diamond. TBIL, total bilirubin; ALB, albumin; G-CSF, granulocyte colony-stimulating factor; CI, confidence interval; SMD, standardized mean difference. Fig. S7. Forest plot of subgroup analysis. (A) Subgroup analysis of the use of G-CSF in terms of ALT at twelve weeks. (B) Subgroup analysis of the use of G-CSF in terms of ALT at twenty-four weeks. (C) Subgroup analysis of the use of G-CSF in terms of AST at twenty-four weeks. The level of ALT at 12 weeks in patients who received stem cells collected directly were significantly different (P < 0.05). The rest of the subgroups were nonsignificantly different (P > 0.05). No significant heterogeneity was observed in the figure B, and C, therefore, a fixed-effect model was used. Since significant heterogeneity was observed in figure A (I2 = 89%), a random-effects model rather was used. In the plane rectangular coordinate system, the forest plot takes a vertical invalid line (scale of abscissa is 0) as the center, describes the effect quantity and 95% CI of each study by using multiple line segments parallel to the horizontal axis, and describes the effect quantity and confidence interval of multiple studies by using a diamond. ALT: alanine aminotransferase; AST: aspartate aminotransferase; G-CSF, granulocyte colony-stimulating factor; CI, confidence interval; SMD, standardized mean difference.

The therapeutic effect of sustained intravitreal injectable voriconazole microspheres (VCZ-MS) on experimental endophthalmitis caused by Aspergillus fumigatus was investigated. VCZ-MS were prepared and evaluated. Vitrectomy was performed on rabbits after intravitreal inoculation of susceptible A. fumigatus. The animals were randomly divided into five groups, including control (no treatment after vitrectomy), vitrectomy plus voriconazole intravitreal injection, and vitrectomy plus intravitreal injection of VCZ-MS containing 0.5, 1.0, or 1.5 mg of voriconazole. The therapeutic effect was assessed at different time intervals. Voriconazole concentrations were monitored in the vitreous injected with VCZ-MS containing 1.0 mg of voriconazole. The results showed that endophthalmitis occurred in all eyes of the control group and rapidly developed into panophthalmitis. The inflammation in the voriconazole and VCZ-MS groups was mild, and in the groups treated with VCZ-MS containing 1.0 or 1.5 mg voriconazole, the inflammation was controlled, the vitreous was clear in all eyes, and there was no recurrence of endophthalmitis. Histopathological examination showed normal structures in the cured eyes, while most uncured eyes were atrophied. Therefore, it can be concluded that an intravitreal injection of VCZ-MS in addition to vitrectomy is an effective treatment for A. fumigatus-induced endophthalmitis in rabbits.

The main purpose of this work was to prepare a self-emulsifying drug delivery system (SEDDS) for a poorly water-soluble drug, puerarin. The solubility of puerarin was determined in various oils and surfactants. Oleic acid and Tween 80 provided relatively higher solubility. The addition of propylene glycol as a cosurfactant improved the solubility of puerarin and the spontaneity of self-emulsification. A series of mixtures composed of oleic acid, propylene glycol, and Tween 80 were prepared and their self-emulsifying properties were studied. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region, and the particle sizes of the resultant emulsions were determined using a laser diffraction sizer. The pharmacokinetic behaviors of three different SEDDS formulations were investigated in beagle dogs. The bioavailability of puerarin was compared using the pharmacokinetic parameters, peak plasma concentration (C(max)), time to reach peak plasma concentration (T(max)), and total area under the plasma concentration-time curve (AUC(0-infinity)). The analysis of the data showed a statistically significant difference between F2 and F4 (P0.01) as well as F3 and F4 (P0.01) with regard to the values of AUC(0-infinity) and C(max) but not between those of F2 and F3 (P0.05). In the case of parameter T(max), ke, no statistically significant difference (P0.05) among the values were observed. From these studies, a SEDDS containing oleic acid (17.5%), Tween 80 (34.5%), and propylene glycol (34.5%) (w/w) was selected as an optimized SEDDS formulation for puerarin. The data suggest the potential use of SEDDS to improve the oral absorption of puerarin.