AIM: To establish the drug release method of Compound Salvia Multi-component released Doublelayer Tablet and investigate its in vitro drug release behavior and the influencing factors of the drug release rate.METHODS: The method of evaluating in vitro release rate of double-layer tablet was established with salvianolic acid B and gindenoside Rg_1 as index,The influencing factors of the release of rapid release layer and sustained release layer of double-layer tablet and their in vitro drug release behavior were studied.RESULTS: The rapid release layer showed the quick releasing effect; The drug release curve of sustained release layer accorded with Ritger-Peppas equation; artificial gastric juice had significant effect on the release curve of gindenoside Rg_1 which in double-layer tablets,but had no significant effect on the release curve of salvianolic acid B.CONCLUSION: The evaluation of in vitro release rate of Compound Salvia Multi-component released Double-layer Tablet shows good properties of fast and sustained release and clinic application is achieved.

The release kinetics research of sustained-release formulations of traditional Chinese medicines (TCM) is an inalienable part of the chain of TCM modernization, which plays an important role in the development of modern compound TCM preparation. However, the research method or pattern in line with the specific characteristics of TCM, i.e., multi-component and multi-target, is still lacking. On the basis of material rough set theory, this paper reviewed the advantages and disadvantages of the existing evaluation patterns and methods, a tentative idea about the "total amount" release characteristics evaluation on TCM compound sustained-release preparation has suggested so as to evaluate the release kinetics and to promote the development of evaluation methodology on TCM sustained-release preparations.

The quality control of traditional Chinese medicine (TCM) preparations is a key issue related to their curative effect, safety and stability. The application of modern analytical means and the development of new disciplines improve the quality control of TCM preparations to some extent. For a long time, however, the quality control level of TCM preparations remains low and the quality standards exist in name only unable to effectively control drug quality and ensure therapeutic effect and safety. The essay makes a systematic analysis on possible factors impacting TCM preparations and current situation of quality control and discusses possible approaches and new methods for improving quality control of TCM preparations, in order to give an impetus to the quality control standards and the mode evolvement of TCM preparations and ensure safety, efficiency and quality controllability of TCM preparations.
Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; methods ; Quality Control

OBJECTIVETo prepare enteric coated pellets containing panax notoginseng saponins.

METHODPanax notoginseng saponins loaded pellets were prepared by Extrusion-Spheronization method, and coated by Eudragit L30D-55 using Glatt fluid bed with the bottom spray process, central composite design was used to optimize the coating prescription.

RESULTThe drug release of enteric coated pellets of panax notoginseng saponins pellets would be lower than 5% in 2 h in simulated gastric fluid, but reach above 85% in 3 h in simulated human gastroenteric environment.

CONCLUSIONThe enteric coated pellets of panax notoginseng saponins have good acid residence to avoid panax notoginseng saponins from degrading in gastric acid.

Chemistry, Pharmaceutical ; methods ; Drug Stability ; Gastric Acid ; chemistry ; Gastrointestinal Tract ; drug effects ; Humans ; Models, Biological ; Panax notoginseng ; chemistry ; Saponins ; chemistry ; pharmacokinetics ; Tablets, Enteric-Coated ; chemistry

Objective:To investigate the effect of stress-induced protein Sestrin2 (SESN2) on necroptosis of mouse dendritic cell (DC) induced by lipopolysaccharide (LPS) combined with zVAD, a panaspartate-specific cysteine protease (caspase) inhibitor.Methods:The DC2.4 cell line derived from the bone marrow of mouse in the 3rd to 10th generations was cultured. The cells were stimulated with LPS for 0 hour, 6 hours, 12 hours, and 24 hours, and grouped according to the stimulation time points. Western blotting was performed to determine the protein expression of SESN2 in each group. Overexpression empty lentivirus (NC), SESN2 gene overexpression RNA sequence lentivirus (SESN2 LV-RNA), small interfering empty lentivirus (NS), and SESN2 gene small interfering RNA sequence lentivirus (SESN2 siRNA) were transfected into DC2.4 cells. After 72 hours of transfection, cell fluorescence expression was observed under the inverted fluorescence microscope. Cells in each transfection group were stimulated with LPS for 24 hours. The blank control groups were set up and cultured with phosphate buffered saline (PBS) for 24 hours. Western blotting was performed to measure SESN2 protein expression. In the same groups as above, cells were stimulated with LPS+zVAD for 24 hours. The blank control groups were set up and cultured with PBS for 24 hours. Western blotting was used to determine the expression of mixed lineage kinase domain-like protein (MLKL) and phosphorylated-MLKL (p-MLKL). The p-MLKL levels and the number of positive cells were observed using laser scanning confocal microscopy. The necroptotic cell ratios were assessed by both flow cytometry and Hoechst staining.Results:Compared to the LPS 0 hour group, the expression of SESN2 in the LPS 24 hours group showed a significant increase. Therefore, 24 hours was chosen as the subsequent stimulation time point. After successful lentivirus transduction and 24 hours of cultivation, the MLKL phosphorylation level in the SESN2 siRNA+LPS+zVAD group was significantly higher than that in the NS+LPS+zVAD group. The MLKL phosphorylation in the SESN2 LV-RNA+LPS+zVAD group was significantly lower than that in the NC+LPS+zVAD group. The MLKL phosphorylation levels in both the NS+LPS+zVAD group and the NC+LPS+zVAD group were obviously higher than those in the NS+PBS group and the NC+PBS group, respectively. Laser scanning confocal microscopy showed that the trends in quantity and fluorescence intensity of p-MLKL protein expressions were consistent with the above results. The results from flow cytometry analysis and Hoechst staining showed that the rates of cell necrotic apoptosis in SESN2 siRNA+LPS+zVAD group were significantly higher than those in NS+LPS+zVAD group [flow cytometry analysis: (30.800±1.153)% vs. (20.800±1.114)%, Hoechst staining: (75.267±0.451)% vs. (46.267±3.371)%, both P < 0.05], indicating that knocking down SESN2 further exacerbated the occurrence of necroptosis. The necrotic apoptosis rates in SESN2 LV-RNA+LPS+zVAD group were significantly lower than those in NC+LPS+zVAD group [flow cytometry analysis: (7.160±0.669)% vs. (19.240±2.322)%, Hoechst staining: (32.433±3.113)% vs. (48.567±4.128)%, both P < 0.05], indicating that overexpressing SESN2 reversed such response and markedly reduced the proportion of necroptotic cells compared to the corresponding empty vector group. Conclusion:SESN2 exhibits an inhibitory effect on necroptosis of DC in sepsis. Targeted SESN2 expression may regulate the process of DC-mediated immune response in sepsis.

Objective:To investigate the effects of stimulator of interferon gene (STING) on ferroptosis mediated by acyl-CoA synthetase long-chain family member 4 (ACSL4) in mouse dendritic cells (DCs) under sepsis, providing a basis for improving the dysregulation of immune response in sepsis caused by factors such as wound infection.Methods:This study was an experimental research. The mouse DC line DC2.4 in the logarithmic growth phase (with passages 3-10) were divided into lipopolysaccharide (LPS) stimulation 0 h (unstimulated) group, LPS stimulation 6 h group, LPS stimulation 12 h group, LPS stimulation 18 h group, and LPS stimulation 24 h group according to the random number table (the same grouping method below), which were cultured with 1 μg/mL LPS (the same concentration below) for the corresponding time. The protein expressions of phosphorylated STING (p-STING), STING, and ACSL4 in cells were determined by Western blotting. DC2.4 successfully transfected with lentivirus containing STING gene small interfering RNA (hereinafter referred to as siSTING) were divided into siSTING+phosphate buffer solution (PBS) group and siSTING+LPS group. DC2.4 successfully transfected with empty lentivirus were divided into empty vector+PBS group and empty vector+LPS group. After being stimulated with PBS or LPS and cultured for 24 hours, the protein expressions of p-STING, STING, and ACSL4 in cells were determined as above. Cell lipid peroxidation degrees were observed using the lipid peroxidation assay kit, and cell apoptosis rates were detected using flow cytometry. The sample numbers in the above cell experiments were all 3. Eighty male C57BL/6J mice aged 6 to 8 weeks were divided into sham surgery+normal saline (NS) group, cecal ligation and puncture (CLP)+NS group, sham surgery+C-176 group, and CLP+C-176 group, with 20 mice in each group. Mice in the two C-176 groups were intraperitoneally injected with C-176, while mice in the two NS groups were intraperitoneally injected with an equivalent volume of NS. One hour later, sham surgery was performed on the mice in the two sham surgery groups, and CLP surgery was performed on the mice in the two CLP groups to establish a sepsis model. At 24 h post-surgery, 10 mice from each group were sacrificed to extract spleen DCs, and protein expression, lipid peroxidation, and apoptosis rates were detected as above ( n=3). Hematoxylin-eosin staining was performed to observe pathological damage in the heart, liver, lung, and kidney tissue. The remaining 10 mice in each group were observed for survival within 7 days after surgery. Results:The protein expressions of p-STING, STING, and ACSL4, as well as the p-STING/STING ratio in DC2.4 in LPS stimulation 24 h group were significantly higher than those in LPS stimulation 0 h group ( P<0.05). After 24 h of culture, the protein expressions of p-STING, STING, and ACSL4 in DC2.4 in siSTING+LPS group and empty vector+PBS group were significantly lower than those in empty vector+LPS group ( P<0.05); the lipid peroxidation degrees of DC2.4 in siSTING+LPS group and empty vector+PBS group were weaker than those in empty vector+LPS group. The apoptosis rates of DC2.4 in empty vector+PBS group, empty vector+LPS group, siSTING+PBS group, and siSTING+LPS group were (15.7±3.0)%, (37.8±2.9)%, (13.1±2.1)%, and (20.6±1.8)%, respectively. The apoptosis rates of DC2.4 in empty vector+PBS group and siSTING+LPS group were significantly lower than that in empty vector+LPS group ( P<0.05). At 24 h post-surgery, the protein expressions of p-STING and ACSL4, and the p-STING/STING ratio in spleen DCs of mice in CLP+NS group were significantly higher than those in sham surgery+NS group and CLP+C-176 group ( P<0.05); the protein expression of STING in spleen DCs of mice in CLP+NS group was significantly higher than that in sham surgery+NS group ( P<0.05); the lipid peroxidation degrees of spleen DCs of mice in CLP+C-176 group and sham surgery+NS group were weaker than that in CLP+NS group. The apoptosis rates of spleen DCs of mice in sham surgery+NS group and CLP+C-176 group were significantly lower than that in CLP+NS group ( P<0.05), and the apoptosis rate of spleen DCs of mice in CLP+C-176 group was significantly higher than that in sham surgery+C-176 group ( P<0.05). Pathological tissue damage in the heart, liver, lung, and kidney of mice in CLP+NS group was significantly worse than that in sham surgery+NS group, while such damage in the above organs of mice in CLP+C-176 group was significantly alleviated compared with that in CLP+NS group. The survival ratio of mice in CLP+NS group within 7 days after surgery was significantly lower than that in sham surgery+NS group ( χ2=8.30, P<0.05). Conclusions:Under sepsis, STING activation in mouse DCs is significant, which enhances ACSL4-mediated ferroptosis. Inhibiting STING activation can significantly reduce ACSL4-mediated ferroptosis level in mouse DCs under sepsis, thereby improving the survival rate of septic mice.

【Objective】 To compare the efficacy and safety of blue laser en bloc enucleation and traditional plasmakinetic electrocautery in the treatment of non-muscle invasive bladder cancer (NMIBC). 【Methods】 A total of 50 NMIBC patients treated in our hospital during Oct.2018 and Dec.2019 were enrolled. A randomized, incomplete blinding, parallel control design and non-inferior test method was adopted. The control group (electrocautery group) used plasmakinetic electrocautery for transurethral resection, and the experimental group (blue laser group) used semiconductor blue laser for transurethral en bloc enucleation. The effective resection rate, operation time, postoperative catheter indwelling time, length of hospital stay, perioperative hemoglobin changes and obturator nerve reflex were compared. 【Results】 There were 24 patients in the blue laser group and 26 in the electrocautery group. The effective dissection rate and hemostasis rate in both groups reached 100%. The blue laser group had slightly longer operation time than the electrocautery group (55 min vs.42 min, P=0.009), but lesser hemoglobin decrease (5.7 g/L vs. 10.4 g/L, P=0.007). There were no significant differences in urinary catheter indwelling time, length of hospital stay and reoperation rate between the two groups. The electrocautery group had 3 cases of obturator nerve reflex, while the blue laser group had none. 【Conclusion】 Compared with the traditional electrocautery, blue laser has good vaporization cutting and coagulation hemostatic effects on bladder tumor tissue, and can completely enucleate tumors in a front-firing model with less bleeding and no obturator nerve reflex, which can be used as a new, efficient, safe and easy-to-learn method for NMIBC surgery. However, its effects on postoperative recurrence rate and progression rate still need further studies.

【Objective】 To investigate the feasibility and safety of semiconductor blue laser in the treatment of non-muscle invasive bladder cancer (NMIBC) in the day surgery model. 【Methods】 The clinical data of 22 NMIBC patients (average age 55.8 years and tumor size 1.4 cm) who underwent outpatient screening and accepted blue laser ambulatory surgery in our hospital during Jun.2022 and Sep.2022 were retrospectively analyzed. On the day of admission, transurethral resection of cancer was performed using blue laser en bloc enucleation. On the day of surgery or in the morning of next day, bladder irrigation was stopped, the catheter was removed, and patients were discharged. The baseline data, pre-hospital waiting time, operation time, length of hospital stay, hemoglobin decrease, complications and management, follow-up, medical costs, and patients’ satisfaction rate were recorded. 【Results】 The pre-hospital waiting time was 2 to 7 days, average (4.1±1.3)days. The operation time was 29 to 50 minutes, average (40.8±5.5)minutes. The length of hospital stay was 0.6 to 1.2 days, average (0.9±0.2)days. Hemoglobin decrease was 1 g/L to 8 g/L, average (3.8±1.8)g/L. The catheter was indwelt for 0.5 to 1 day, average (0.7±0.1)day. The medical costs were 13 790 to 16 811 Yuan, average (14 941.5±690.2) Yuan. Patients’ satisfaction rate was 100.0%. Mild intraoperative and postoperative complications occurred in 2 cases. One patient developed symptoms of cystitis which disappeared after 2 days of oral antibiotic cefixime, and another patient developed bladder spasm which was relieved after oral solifenacin succinate tablets. No adverse events such as obturator nerve reflex or bladder perforation occurred. After removal of the catheter, no urinary retention was observed. 【Conclusion】 This study was the first to apply blue laser ambulatory surgery in the treatment of bladder cancer, confirming that it is a safe, feasible, economical and efficient model for selected patients, which can be promoted in suitable hospitals.