Oral hydroxycamptothecin nanosuspension (HCPT-Nano) with high supersaturated dissolution level, high permeation and well physical stability, was manufactured by microprecipitation-high press homogenization method. Its pharmaceutical properties were investigated, such as size and distribution, zeta potential, particle shape, physical existence condition, supersaturated dissolution level and so on. Particle size was measured by laser diffraction, and the mean diameters before and after lyophilization were 138 +/- 11.72 nm and 175 +/- 12.74 nm, respectively, for HCPT-Nano. Zeta potentials of HCPT-Nano was over -20 mV. The nanoparticles, being observed by transmission electron microscopy (TEM), were claviform or column in shape. DSC and X-ray diffraction revealed that HCPT existed in the form of crystal for HCPT-Nano. And HCPT-Nano could maintain higher supersaturated dissolution level for long time. So it supplied the possibility of improving oral bioavailability of HCPT when combining together admoveatur of P-gp inhibitor, CsA.

Objective To evaluate the effect of chidamide combined with matrine on proliferation and apoptosis of cutaneous T-cell lymphoma (CTCL) cell lines HH and Hut78,and to explore their apoptotic mechanisms.Methods Both HH and Hut78 cells were treated with 0.4 μmol/L chidamide and 0.6 g/L matrine alone or in combination for 24,48 and 72 hours,with those treated with dimethyl sulfoxide (DMSO) serving as control groups.MTS assay was performed to deteet cellular proliferation rates of HH and Hut78 cells at each time point.After 48-hour treatment,flow cytometry was conducted to detect cell apoptosis,and Western blot analysis to determine expression of apoptosis-related proteins in these cells.Statistical analysis was carried out by using repeated measures analysis of variance,one-way analysis of variance,and least significant difference (LSD)-t test for multiple comparisons.Results Compared with DMSO,chidamide and matrine alone or in combination could inhibit the proliferation of HH and Hut78cells to different extents (F =15.88,558.26,P ＜ 0.05,＜ 0.001,respectively).At 48 hours,the apoptosis rate in Hut78 cells was significantly higher in the matrine group (20.98％ ± 1.53％),chidamide group (22.44％ ± 7.74％) and combination group (44.53％ ± 1.85％) than in the control group (8.42％ ± 4.23％;LSD-t =4.76,5.31,13.69 respectively,all P ＜ 0.05),as well as in the combination group than in the matrine group and chidamide group (LSD-t =8.93,8.37 respectively,both P ＜ 0.01);no significant differences were observed in the apoptosis rate of HH cells between the matrine group (13.98％ ± 3.86％)or chidamide group (13.61％ ± 1.62％) and control group (11.44％ ± 1.43％,both P ＞ 0.05),while the combination group (20.94％ ± 0.64％) showed a significantly higher apoptosis rate compared with the control group,matrine group and chidamide group (LSD-t =7.37,5.40,5.69 respectively,all P ＜ 0.05).In the case of HH cells,the combination group showed significantly higher cleaved caspase-3 expression (all P ＜ 0.05),but significantly lower protein expression of E-cadherin,nuclear factor (NF)-κB,phosphorylated-Bad (p-Bad) and Bcl-2 compared with the other 3 groups (all P ＜ 0.05).In the case of Hut78 cells,the expression of E-cadherin,NF-κB,p-Bad and Bcl-2 was significantly lower in the matrine group,chidamide group and combination group than in the control group (all P ＜ 0.05),while cleaved caspase-3 expression was significantly higher in the chidamide group and combination group than in the control group (both P ＜0.05).No matter in HH cells or in Hut78 cells,there were no significant differences in Bad protein expression between the 4 groups (all P ＞ 0.05).Conclusion Chidamide in combination with matrine can inhibit proliferation and induce apoptosis of HH and Hut78 cells,likely by regulating the expression of apoptosis-related proteins E-cadherin,NF-κB,p-Bad,Bcl-2 and cleaved caspase-3.

Objective:To investigate the prenatal MRI diagnosis of fetal intracranial hemorrhage (ICH) and the pregnancy outcomes.Methods:This retrospective study included 49 cases of fetal ICH diagnosed by MRI in Obstetrics and Gynecology Hospital of Fudan University from July 2011 to November 2019. Two experts with more than five years of experience in obstetric radiology determined the location, number, area, stage and grade of the hemorrhage based on the MRI findings. Maternal age, gestational age at MRI, and the site, number, stage and grade of hemorrhage as well as other intracranial and extracranial abnormalities of the fetuses were compared between women with fetal germinal matrix-intraventricular hemorrhage (GM-IVH; GM-IVH group, n=39) and those without (non-GM-IVH group, n=10). MRI and ultrasound examination results of 37 cases who had MRI within three days after the ultrasound examination were compared. Postnatal and follow-up outcomes were summarized. Statistical analysis was performed using the independent sample t-test, Mann-Whitney U test and Chi-square test. Results:There was no significant difference in the maternal age, gestational age at MRI, or the site, number or stage of hemorrhage between the GM-IVH group and non-GM-IVH group (all P>0.05). The incidence of ventriculomegaly was higher in the GM-IVH group than that in the non-GM-IVH group [87% (34/39) vs 0/10, t=24.522, P<0.001]. There were 51% (19/37) of the lesions that were missed by ultrasound found by MRI, including GM-IVH in 17 cases, right cerebellar hemisphere hemorrhage in one case and corpus callosum hemorrhage in one case. Among the 49 cases, seven were lost to follow-up, 29 terminated the pregnancy (six in non-GM-IVH group and 23 in GM-IVH group), two experienced intrauterine fetal death in late pregnancy and 11 gave live birth. Ten live births had GM-IVH, among them a relatively good prognosis was noted in fetuses with grade Ⅰ (two cases), grade Ⅱ (four cases), and grade Ⅲ (three cases) GM-IVH, while one case with grade Ⅳ GM-IVH had mental retardation at eight years old; one non-GM-IVH infant had hearing loss at birth and a cochlear was implanted with no other anomalies reported during a three-year follow-up. Conclusions:MRI can provide a more direct view of the location and grade of fetal ICH and is more accurate than prenatal ultrasound in diagnosing fetal ICH, which is a beneficial supplement to ultrasound. The prognosis of cases with grade Ⅳ GM-IVH is not good.

Objective:To investigate the value of cystatin C (Cys-C) in the early diagnosis of acute kidney injury (AKI) after radical nephrectomy and the predictive value for the prognosis of Cys-C based estimated glomerular filtration rate (eGFR Cys-C) after surgery. Methods:The clinical data of 118 patients who underwent unilateral radical nephrectomy in our hospital from January 2019 to December 2020 were retrospectively analyzed. According to the diagnostic criteria of AKI, they were divided into AKI group of 75 cases and no-AKI group of 43 cases. AKI group was (62.7±10.7) years old, with 49 males and 26 females. The no-AKI group was (62.3±12.8) years old, with 21 males and 22 females. The urea nitrogen was (4.9±1.3) mmol/L, creatinine (75.7±14.5)μmol/L, Cys-C (0.85±0.22) mg/L, eGFR Cr(76.3±11.2)ml/(min·1.73m 2), and eGFR Cys-C(101.4±17.4)ml/(min·1.73m 2)in AKI group before operation.In no-AKI group, preoperative urea nitrogen was (4.9±1.5) mmol/L, creatinine (74.5±13.1)μmol/L, Cys-C (0.81±0.29) mg/L, eGFR Cr(78.6±12.5)ml/(min·1.73m 2), and eGFR Cys-C(99.3±18.8)ml/(min·1.73m 2), and there were no significant differences in the values of urea nitrogen, creatinine, Cys-C and eGFR between the two groups before surgery ( P>0.05). ROC curve was used to analyze the diagnostic value of urea nitrogen, creatinine, Cys-C, eGFR calculated based on creatinine and Cys-C at 48h after surgery, and binary Logistic regression was used to analyze the risk factors for AKI. The creatinine status of patients diagnosed with SPS was evaluated 6 months after surgery, based on the definition of Cys-C based eGFR being less than 70% of creatinine-based eGFR(SPS=eGFR Cys-C/ eGFR Cr≤0.7). Results:In AKI group, creatinine was(115.2±22.1)μumol/L, Cys-C (1.8±0.27) mg/L, eGFR Cr (51.6±9.6)ml/(min·1.73m 2), and eGFR Cys-C(43.4±8.5)ml/(min·1.73m 2)48 h after operation. The creatinine was(92.7±13.3)μmol/L, Cys-C(1.3±0.23) mg/L, eGFR Cr(62.2±11.3)ml/(min·1.73m 2), and eGFR Cys-C(61.5±9.5)ml/(min·1.73m 2) in no-AKI group, and difference were statistically significant between the two groups ( P<0.01). ROC curve was used to analyze the diagnosis of AKI. Creatinine, Cys-C, eGFR Cr and eGFR Cys-Cwere all of diagnostic value for AKI (all P<0.01), and AUC(Area under curve) were 0.809, 0.889, 0.761 and 0.925 respectively. The sensitivity, specificity and area under the curve of eGFR Cys-C were 93.3%, 74.4% and 92.5% respectively. Binary Logistic regression analysis showed that creatinine( OR=10.851, 95% CI 2.322-50.688, P=0.004), Cys-C( OR=10.016, 95% CI 2.306-43.362, P=0.001), eGFR Cr( OR=17.923, 95%CI 3.216-53.172, P=0.001) and eGFR Cys-C( OR=19.817, 95% CI 3.367-55.263, P=0.001)were all independent risk factors for AKI. The predictive accuracy of eGFR Cys-C, creatinine, Cys-C, eGFR Cr were 91.6%, 85.7%, 90.2%, 88.5%, respectively. There were 15 cases were confirmed SPS in the AKI group, and only 2 cases were confirmed SPS in the no-AKI group, indicating patients in the AKI group developed more SPS than those in the no-AKI group, with statistically significant difference(Kappa value was 5.22, P=0.02). The 6-month follow-up showed that the creatinine of confirmed SPS was (103.8±23.4)μmol/L and the creatinine of unconfirmed SPS was (86.8±27.2)μmol/L, with statistically significant difference ( P<0.01). Conclusions:eGFR Cys-C calculated based on Cys-C has high sensitivity in diagnosing AKI and has early diagnostic value. Patients diagnosed with SPS based on eGFR Cys-C had higher creatinine 6 months after surgery.