OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Objective: Miniscrews are commonly utilized as temporary anchorage devices (TADs) in cases of maxillary protrusion and premolar extraction. This study aimed to investigate the effects and potential side effects of two conventional miniscrew configurations on the maxillary incisors. Methods: Eighty-two adult patients with maxillary dentoalveolar protrusion who had undergone bilateral first premolar extraction were retrospectively divided into three groups: non-TAD, two posterior miniscrews only (P-TADs), and two anterior and two posterior miniscrews combined (AP-TADs). Cone-beam computed tomography was used to evaluate the maxillary central incisors (U1). Results: The APTADs group had significantly greater U1 intrusion (1.99 ± 2.37 mm, n = 50) and less retroclination (1.70° ± 8.80°) compared to the P-TADs (–0.07 ± 1.65 mm and 9.45° ± 10.68°, n = 60) and non-TAD group (0.30 ± 1.61 mm and 1.91° ± 9.39°, n = 54).However, the AP-TADs group suffered from significantly greater apical root resorption (ARR) of U1 (2.69 ± 1.38 mm) than the P-TADs (1.63 ± 1.46 mm) and non-TAD group (0.89 ± 0.97 mm). Notably, the incidence of grade IV ARR was 16.6% in the AP-TADs group, significantly higher than the rates observed in the P-TADs (6.7%) and non-TAD (1.9%) groups. Multiple regression analysis revealed that after excluding tooth movement factors, the AP-TADs configuration resulted in an additional 0.5 mm of ARR compared with the P-TADs group. Conclusions In cases of maxillary protrusion and premolar extraction, the use of combined anterior and posterior miniscrews enhances incisor intrusion and minimizes torque loss of the maxillary incisors. However, this approach results in more severe ARR, likely due to the increased apical movement and composite force exerted.

Objective: Miniscrews are commonly utilized as temporary anchorage devices (TADs) in cases of maxillary protrusion and premolar extraction. This study aimed to investigate the effects and potential side effects of two conventional miniscrew configurations on the maxillary incisors. Methods: Eighty-two adult patients with maxillary dentoalveolar protrusion who had undergone bilateral first premolar extraction were retrospectively divided into three groups: non-TAD, two posterior miniscrews only (P-TADs), and two anterior and two posterior miniscrews combined (AP-TADs). Cone-beam computed tomography was used to evaluate the maxillary central incisors (U1). Results: The APTADs group had significantly greater U1 intrusion (1.99 ± 2.37 mm, n = 50) and less retroclination (1.70° ± 8.80°) compared to the P-TADs (–0.07 ± 1.65 mm and 9.45° ± 10.68°, n = 60) and non-TAD group (0.30 ± 1.61 mm and 1.91° ± 9.39°, n = 54).However, the AP-TADs group suffered from significantly greater apical root resorption (ARR) of U1 (2.69 ± 1.38 mm) than the P-TADs (1.63 ± 1.46 mm) and non-TAD group (0.89 ± 0.97 mm). Notably, the incidence of grade IV ARR was 16.6% in the AP-TADs group, significantly higher than the rates observed in the P-TADs (6.7%) and non-TAD (1.9%) groups. Multiple regression analysis revealed that after excluding tooth movement factors, the AP-TADs configuration resulted in an additional 0.5 mm of ARR compared with the P-TADs group. Conclusions In cases of maxillary protrusion and premolar extraction, the use of combined anterior and posterior miniscrews enhances incisor intrusion and minimizes torque loss of the maxillary incisors. However, this approach results in more severe ARR, likely due to the increased apical movement and composite force exerted.

Objective: Miniscrews are commonly utilized as temporary anchorage devices (TADs) in cases of maxillary protrusion and premolar extraction. This study aimed to investigate the effects and potential side effects of two conventional miniscrew configurations on the maxillary incisors. Methods: Eighty-two adult patients with maxillary dentoalveolar protrusion who had undergone bilateral first premolar extraction were retrospectively divided into three groups: non-TAD, two posterior miniscrews only (P-TADs), and two anterior and two posterior miniscrews combined (AP-TADs). Cone-beam computed tomography was used to evaluate the maxillary central incisors (U1). Results: The APTADs group had significantly greater U1 intrusion (1.99 ± 2.37 mm, n = 50) and less retroclination (1.70° ± 8.80°) compared to the P-TADs (–0.07 ± 1.65 mm and 9.45° ± 10.68°, n = 60) and non-TAD group (0.30 ± 1.61 mm and 1.91° ± 9.39°, n = 54).However, the AP-TADs group suffered from significantly greater apical root resorption (ARR) of U1 (2.69 ± 1.38 mm) than the P-TADs (1.63 ± 1.46 mm) and non-TAD group (0.89 ± 0.97 mm). Notably, the incidence of grade IV ARR was 16.6% in the AP-TADs group, significantly higher than the rates observed in the P-TADs (6.7%) and non-TAD (1.9%) groups. Multiple regression analysis revealed that after excluding tooth movement factors, the AP-TADs configuration resulted in an additional 0.5 mm of ARR compared with the P-TADs group. Conclusions In cases of maxillary protrusion and premolar extraction, the use of combined anterior and posterior miniscrews enhances incisor intrusion and minimizes torque loss of the maxillary incisors. However, this approach results in more severe ARR, likely due to the increased apical movement and composite force exerted.

Objective: Miniscrews are commonly utilized as temporary anchorage devices (TADs) in cases of maxillary protrusion and premolar extraction. This study aimed to investigate the effects and potential side effects of two conventional miniscrew configurations on the maxillary incisors. Methods: Eighty-two adult patients with maxillary dentoalveolar protrusion who had undergone bilateral first premolar extraction were retrospectively divided into three groups: non-TAD, two posterior miniscrews only (P-TADs), and two anterior and two posterior miniscrews combined (AP-TADs). Cone-beam computed tomography was used to evaluate the maxillary central incisors (U1). Results: The APTADs group had significantly greater U1 intrusion (1.99 ± 2.37 mm, n = 50) and less retroclination (1.70° ± 8.80°) compared to the P-TADs (–0.07 ± 1.65 mm and 9.45° ± 10.68°, n = 60) and non-TAD group (0.30 ± 1.61 mm and 1.91° ± 9.39°, n = 54).However, the AP-TADs group suffered from significantly greater apical root resorption (ARR) of U1 (2.69 ± 1.38 mm) than the P-TADs (1.63 ± 1.46 mm) and non-TAD group (0.89 ± 0.97 mm). Notably, the incidence of grade IV ARR was 16.6% in the AP-TADs group, significantly higher than the rates observed in the P-TADs (6.7%) and non-TAD (1.9%) groups. Multiple regression analysis revealed that after excluding tooth movement factors, the AP-TADs configuration resulted in an additional 0.5 mm of ARR compared with the P-TADs group. Conclusions In cases of maxillary protrusion and premolar extraction, the use of combined anterior and posterior miniscrews enhances incisor intrusion and minimizes torque loss of the maxillary incisors. However, this approach results in more severe ARR, likely due to the increased apical movement and composite force exerted.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.