The anti-tumor activity of folate receptor targeting docetaxel-loaded membrane-modified liposomes (FA-PDCT-L) was investigated in vitro and in vivo. FA-PDCT-L was prepared by organic solvent injection method. Transmission electron microscope, dynamic light scattering and electrophoretic light scattering were employed to study the physicochemical parameters of FA-PDCT-L. The inhibitory effects of docetaxel injection (DCT-I), non-modified DCT liposomes (DCT-L) and FA-PDCT-L on the growth of MCF-7 and A-549 cells at different incubation times were detected by CCK-8 assay; and the hemolytic test was employed in vitro. Tumor mice were randomized into 4 groups: DCT-I, DCT-L, FA-PDCT-L and control group (normal saline), and given drugs at 10 mg x kg(-1) x d(-1) through tail vein. The tumor volume, mice weight, inhibition rate of tumor and life span were measured at the end of experiments. The IC50 of the FA-PDCT-L for MCF-7 and A549 cell lines were significantly lower than that of DCT-I and DCT-L, without hemolysis reaction observed. Compared with control group, the weights of tumor in DCT-I, DCT-L and FA-PDCT-L were decreased, especially for FA-PDCT-L, with inhibitory rates at 79.03 % (P < 0.05). The life span and median survival time of FA-PDCT-L treated mice were significantly higher than that of DCT-I and DCT-L. In conclusion, FA-PDCT-L shows a good anti-tumor activity, indicating that it is potential carriers for DCT in the treatment of tumor.

OBJECTIVE:To prepare and characterize capreomycin sulfate liposomes(CSL).METHODS:Capreomycin sulfate was entrapped into liposomes using active loading that pH gradient methods,ammonium sulfate gradient methods and sodium acetate gradient methods respectively followed by lyophilization technique.The liposome was characterized by entrapment efficiency,particle size,? potential and the stability.RESULTS:The entrapment efficiency of CSL pre-and post-lyophilization prepared by three methods were 65.7% and 65.2 %,20.1% and 18.6%,34.6% and 32.4%,with particle size of 136 and 145 nm,144 and 153 nm,142 and 159 nm,? potential of —20.2 and —19.5 mV,—24.4 and —22.9 mV,—18.7 and —17.8 mV respectively.No obvious changes were found in all the indexes in the stability test.CONCLUSIONS:The pH gradient technique is suitable for preparing CSL in 3 kinds of methods.

OBJECTIVE: To establish a RP-HPLC method for the determination of pamidronate disodium. METHODS: The determination was performed on C18 column with acetonitrile-0.4% sodium hydroxide solution of EDTA-Na2 (14∶86) as mobile phase at a flow rate of 0.6mL?min-1,the sample size was 10?L and the detection was performed by fluorescence detector with excitation wavelength at 395nm and emission wavelength at 480nm. RESULTS: The linear range of pamidronate disodium was 7.2～16.8?g?mL-1(r=0.999 8,n=9),the recovery rate was 100.11%(RSD=0.7%, n=9). CONCLUSIONS: The established method is simple and accurate.

Oxaliplatin-loaded nanostuctured lipid carriers (OP-NLC) were prepared by ultrasonic emulsification method. And its optimal prescription was selected by orthogonal design. The laser light scattering technique, zeta potential analyzer, TEM, DSC, XRD and HPLC were employed to study the physicochemical parameters of OP-NLC, which displayed in terms of particle size, zeta potential, crystalline, drug loading and encapsulation efficiency. The results showed that OP-NLC had an average diameter of (111 +/- 20) nm, zeta potential of (-27.4 +/- 13.1) mV, encapsulation efficiency of (77.4 +/- 2.5) % and drug content of (0.8 +/- 1.5) mg mL(-1). TEM, DSC and XRD indicated that OP-NLC was spherical and the drug was dispersed as nanoparticles by means of non-crystalline. The in vitro release test showed that the drug could be sustained-released from NLC in buffer solution (pH 4.5) after a burst release in initial phase.

Silibinin exhibits antidiabetic potential by preserving the mass and function of pancreatic β-cells through up-regulation of estrogen receptor-α (ERα) expression. However, the underlying protective mechanism of silibinin in pancreatic β-cells is still unclear. In the current study, we sought to determine whether ERα acts as the target of silibinin for the modulation of antioxidative response in pancreatic β-cells under high glucose and high fat conditions. Our in vivo study revealed that a 4-week oral administration of silibinin (100 mg/kg/day) decreased fasting blood glucose with a concurrent increase in levels of serum insulin in high-fat diet/streptozotocin-induced type 2 diabetic rats. Moreover, expression of ERα, NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in pancreatic β-cells in pancreatic islets was increased by silibinin treatment. Accordingly, silibinin (10 μM) elevated viability, insulin biosynthesis, and insulin secretion of high glucose/palmitate-treated INS-1 cells accompanied by increased expression of ERα, Nrf2, and HO-1 as well as decreased reactive oxygen species production in vitro. Treatment using an ERα antagonist (MPP) in INS-1 cells or silencing ERα expression in INS-1 and NIT-1 cells with siRNA abolished the protective effects of silibinin. Our study suggests that silibinin activates the Nrf2-antioxidative pathways in pancreatic β-cells through regulation of ERα expression.

Rheumatoid arthritis is a chronic, systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate. Several drugs have been used for the treatment of rheumatoid arthritis, but their use is limited by suboptimal bioavailability, serious adverse effects, and nonnegligible first-pass effects. In contrast, transdermal drug delivery systems (TDDSs) can avoid these drawbacks and improve patient compliance, making them a promising option for the treatment of rheumatoid arthritis (RA). Of course, TDDSs also face unique challenges, as the physiological barrier of the skin makes drug delivery somewhat limited. To overcome this barrier and maximize drug delivery efficiency, TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology, and different generations of TDDSs have been derived, which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery. In this review, we summarize the different generations of transdermal drug delivery systems, the corresponding transdermal strategies, and their applications in the treatment of RA.

OBJECTIVE: To investigate the effect of improved nursing strategy on prognosis of older immunosuppressed patients with pneumonia and sepsis. METHODS: A prospective study was conducted. The older immunosuppressed patients with pneumonia and sepsis admitted to the department of intensive care medicine and emergency intensive care unit (ICU) of Peking Union Medical College Hospital from January 2017 to July 2022 were enrolled. In the first stage (from January 2017 to December 2019), patients received the original nursing strategy (original nursing strategy group), including: (1) nurses were randomly assigned; (2) routine terminal cleaning; (3) ICU environmental cleaning twice a day; (4) oral care was performed with chlorhexidine twice a day; (5) original lung physiotherapy [head of bed elevated at 30 degree angle-45 degree angle, maintaining a Richmond agitation-sedation scale (RASS) -2 to 1, sputum aspiration as needed]. After 1 month of learning and training of the modified nursing treatment strategy for nurses and related medical staff, the patients in the second stage (from February 2020 to July 2022) received the improved nursing strategy (improved nursing strategy group). The improved nursing strategy improved the hospital infection prevention and control strategy and lung physical therapy strategy on the basis of the original nursing strategy, including: (1) nurses were fixed assigned; (2) patients were placed in a private room; (3) enhanced terminal cleaning; (4) ICU environmental cleaning four times a day; (5) education and training in hand hygiene among health care workers was improved; (6) bathing with 2% chlorhexidinegluconate was performed once daily; (7) oral care with a combination of chlorhexidine and colistin was provided every 6 hours; (8) surveillance of colonization was conducted; (9) improved lung physiotherapy (on the basis of the original lung physiotherapy, delirium score was assessed to guide early mobilization of the patients; airway drainage was enhanced, the degree of airway humidification was adjusted according to the sputum properties, achieving sputum viscosity grade II; lung ultrasound was also used for lung assessment, and patients with atelectasis were placed in high lateral position and received the lung recruitment maneuver). Baseline patient information were collected, including gender, age, underlying diseases, source of admission, disease severity scores, vital signs, ventilatory parameters, blood gas analysis, life-sustaining treatments, clinical laboratory evaluation, indicators of infection and inflammation, pathogens and drug therapy. The primary outcome was 28-day mortality, and the secondary outcomes were duration of mechanical ventilation, length of ICU stay, and ICU mortality. Multivariate Logistic regression analysis was used to determine the risk factors for 28-day death in older immunosuppressed patients with pneumonia and sepsis. RESULTS: Finally, 550 patients were enrolled, including 199 patients in the original nursing strategy group and 351 patients in the improved nursing strategy group. No significant differences were found in gender, age, underlying diseases, source of admission, disease severity scores, vital signs, ventilatory parameters, blood gas analysis, life-sustaining treatments, clinical laboratory evaluation, indicators of infection and inflammation, coexisting pathogens or drug therapy between the two groups. Compared with patients in the original nursing strategy group, those in the improved nursing strategy group had significantly fewer duration of mechanical ventilation and length of ICU stay [duration of mechanical ventilation (days): 5 (4, 7) vs. 5 (4, 9), length of ICU stay (days): 11 (6, 17) vs. 12 (6, 23), both P < 0.01], and lower ICU mortality and 28-day mortality [ICU mortality: 23.9% (84/351) vs. 32.7% (65/199), 28-day mortality: 23.1% (81/351) vs. 33.7% (67/199), both P < 0.05]. Multivariate Logistic regression analysis showed that the improved nursing strategy acted as an independent protective factor in 28-day death of older immunosuppressed patients with pneumonia and sepsis [odds ratio (OR) = 0.543, 95% confidence interval (95%CI) was 0.334-0.885, P = 0.014]. CONCLUSIONS Improved nursing strategy shortened the duration of mechanical ventilation and the length of ICU stay, and decreased ICU mortality and 28-day mortality in older immunosuppressed patients with pneumonia and sepsis, significantly improving the short-term prognosis of such patients.
Humans ; Aged ; Prospective Studies ; Chlorhexidine/therapeutic use* ; Intensive Care Units ; Pneumonia ; Prognosis ; Sepsis/therapy* ; Inflammation