OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial （IIT）. METHODS With benchmarking analysis， based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai， a thorough review was conducted， involving relevant laws， regulations， and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects， a detailed comparative analysis of key processes was carried out， such as the receipt， storage， distribution， use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing， the training before project implementation was insufficient， and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems， improvement measures were put forward， including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs， etc. The related systems were improved， and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established， which helps to improve the institutional X2023076） framework of medical institutions in this field.

OBJECTIVE To establish management index system for rational drug use of key monitoring drugs， and provide reference for the management of key monitoring drugs in the hospitals. METHODS First， the management index system for rational drug use of key monitoring drugs was drafted by collecting the evidence from related medical literature. Next， using a modified Delphi method， twenty experienced experts from the fields of pharmacy， medical practice， healthcare insurance， and finance were selected to participate in two rounds of questionnaire consultations. Based on the expert enthusiasm coefficient， authority coefficient， degree of opinion concentration， and degree of coordination， the final indicators were determined to establish a management index system for rational drug use of key monitored drugs in medical institutions. RESULTS The expert enthusiasm coefficients reached 100% in both rounds of consultation. In first-level， second-level and third-level indicators， the authority coefficients of experts were 0.89， 0.86 and 0.87， and coordination coefficients of the experts in importance score were 0.300 （P＜ 0.05）， 0.125 （P＜0.05） and 0.139 （P＜0.05）， respectively. The average score for the importance of all indicators reached over 3.5， in which the full score ratio ranged from 35% to 100%. Except that the variation coefficient of a third-level indicator “number of specifications purchased for key monitored drugs” was 0.26， the variation coefficients of rest indicators were less than or equal to 0.25. Based on the results of expert consultation， final version of the management index system established in this study， including two first-level indicators （drug procurement and use， and rational drug use）， five second-level indicators （such as the accessibility， cost-effectiveness） and twenty third-level indicators （such as the number of specifications purchased for key monitored drugs， the increase in the cost of key monitored drugs）. CONCLUSIONS The management index system established in this study possesses high reliability and strong operability， and may provide a reference for the management of key monitoring drugs in the hospitals.

Objective: To compare the biological characteristics of human induced pluripotent stem cell-derived platelet exosomes (hiPSC-Plt-Exos) with those of conventional apheresis platelet exosomes (Plt-Exos), specifically focusing on their differential abilities to enhance the proliferation and migration of human umbilical cord mesenchymal stem cells (hUC-MSCs). Methods: Exosomes were isolated from hiPSC-derived Plt and apheresis Plt concentrate using size exclusion chromatography. These exosomes were then characterized through nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. Co-culture experiments into hUC-MSCs were conducted with hiPSC-Plt-Exos and apheresis Plt-Exos, respectively. Their effects on the proliferation and migration of hUC-MSCs were assessed via cell proliferation assays and scratch tests. Results: hiPSC-Plt-Exos and apheresis Plt-Exos exhibited comparable particle sizes, morphological features (such as the characteristic cup-shaped structure), and surface markers (including CD9 and HSP70). Notably, hiPSC-Plt-Exos demonstrated a significantly greater ability to enhance the proliferation and migration of hUC-MSCs compared to apheresis Plt-Exos (P<0.05). These differences provide critical comparative data for their application in various clinical contexts. Conclusion: This study establishes a theoretical foundation for developing precise therapeutic strategies based on hiPSC-Plt-Exos. Furthermore, it underscores the necessity of selecting the appropriate type of exosomes according to the specific disease microenvironment to achieve optimal therapeutic outcomes.

The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10^-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Objective To observe clinical outcomes of propofol and remazolam in patients undergoing elective painless fiberoptic bronchoscopic biopsy.Methods Patients who underwent painless fibreoptic bronchoscopic biopsy in our hospital from March 2022 to April 2023 were selected for the study and divided into 2 groups using simple randomisation method.In the control group,anaesthesia was induced with 1 mg·kg-1 propofol,3 μg·kg-1 fentanyl,0.1 mg·kg-1 cis-atracurium,and anaesthesia was maintained with 4-6 mg·kg-1·h-1 propofol.In the treatment group,anaesthesia was induced with 0.2 mg·kg-1 remazolam,3 μg·kg-1 fentanyl,0.1 mg·kg-1 cis-atracurium,and anaesthesia was maintained with 0.2-0.4 mg·kg-1·h-1 remazolam.We compared the awakening time,laryngeal mask removal time,microscopy time,and the proportion of additional anaesthetics in the 2 groups,and detected the levels of S100β,neuron-specific enolase(NSE),interleukin-6(IL-6),tumour necrosis factor-alpha(TNF-α)in the 2 groups preoperatively and at 24 h postoperatively,and statistically counted the occurrences of adverse reactions in the 2 groups.Results The time for pulling out the laryngeal mask in the treatment group was significantly lower than that in the control group,while the time for microscopy,time for awakening,and proportion of additional anaesthesia drugs were not statistically significant when compared with that in the control group(all P＞0.05).The overall anaesthesia effect grading of the test group was not statistically significant when compared with the control group(P＞0.05).S100β were(0.66±0.17)and(0.78±0.21)μg·L-1;NSE were(8.47±1.78)and(11.47±2.06)μg·L-1;IL-6 were(8.64±1.21)and(12.89±1.47)pg·mL-1;TNF-α were(6.27±1.07)and(9.13±1.41)pg·mL-1,respectively,which were higher than that of preoperative period,and the treatment group was lower than that of the control group at 24 h postoperatively,and the difference was statistically significant(all P＜0.05).The incidence of adverse drug reactions in the treatment group and the control group were 13.75％and 22.50％,respectively,and the difference was not statistically significant(P＞0.05).Conclusion The use of remazolam in painless fiberoptic bronchoscopic biopsy is less neurologically damaging,stabilizes hemodynamics.

Objective:To investigate the associated factors of depressive symptoms among patients with neo-plasms.Methods:Nationwide(excluding Hong Kong,Macao,and Taiwan),30 505 residents were selected by a combination of stratified sampling and quota sampling according to the proportion of the seventh national population census.Patient Health Questionnaire-9(PHQ-9),General Anxiety Disorder-7(GAD-7),self-made questionnaire,and simplified perceived social support scale used to evaluate depressive symptoms,anxiety symptoms,behaviors,and perceived social support among patients with neoplasms.Results:Totally 359(1.2％)patients with self-repor-ted clinically diagnosed neoplasms were included,of which 151(42.1％)patients with malignant neoplasms and 208(57.9％)patients with benign neoplasms.The detection rate of depressive symptoms in patients with neo-plasms was 76.6％.Less than three days of walking for more than 10 minutes per day in the past week(OR=6.63),4-6 days of walking for more than 10 minutes per day in the past week(OR=5.00),the low(OR=4.80)or medium(OR=3.06)overall sleep quality,the lower perceived friend support(OR=4.66),and anxiety symp-toms(OR=1.74)among patients with neoplasms were risk factors for depressive symptoms.Conclusion:Patients with neoplasms generally might be at a high risk of depressive symptoms,especially for those patients with less ex-ercise,poor sleep quality,and low perceived social support.

The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.

OBJECTIVE To improve the quality evaluation method of Platycodonis Radix, to study the differences in the quality of three-years-old Platycodonis Radix under different harvesting periods, and to determine the optimal harvesting period of Platycodonis Radix. METHODS The leachate, ash, moisture, refractive index and the content of six saponins were used as the quality evaluation indexes. The differences between the herbs of Platycodonis Radix at different harvesting periods were characterized with the help of mathematical and statistical methods. And link the entropy weight method, gray correlation analysis and TOPSIS method were combined to obtain the statistical analysis of the relevant indexes and the quality ranking information of the herbs in different harvesting periods. RESULTS There were significant differences between the quality evaluation indexes of three-years-old Platycodonis Radix at different harvesting periods. The added multi-indicator testing had improved the quality evaluation system of Platycodonis Radix and enhanced the "Drug properties-Effectiveness" linkage of the herbs. And the results of the comprehensive quality evaluation model showed that the herbs harvested around October 21 (Frost’s Descent) were ranked best in terms of comprehensive index. CONCLUSION In order to ensure the quality of Platycodonis Radix, the best harvesting period for three-years-old Platycodonis Radix is determined around the "Frost’s Descent" season, taking into account the characteristics of the herbs' appearance and the material basis of herbs.

AIM: To assess the repeatability and agreement of higher-order aberration obtained by adaptive optics visual simulator(VAO)compared with OPD-Scan Ⅲ.METHODS: A cross-sectional study was conducted from August to September 2023, including a total of 204 patients(204 eyes)with myopia whose right eyes were measured. The examinations were performed by the same skilled examiner using both devices separately. The VAO device was used to measure higher order aberrations of orders 3 to 6 at a pupil diameter of 4.5 mm, while both the VAO and OPD-Scan Ⅲ devices were utilized to measure total higher-order aberration(tHOA), spherical aberration(SA), coma aberration(Coma), and trefoil aberration(Trefoil)of the entire eye at pupil diameters ranging from 3 to 6 mm. Furthermore, the repeatability of whole eye aberration measurements obtained with the VAO device was evaluated and the agreement of the two devices was assessed.RESULTS: The whole-eye higher-order aberrations measured by VAO demonstrated excellent repeatability(0.767≤ICC≤0.941, Sw<0.01 μm, TRT<0.1 μm). There was no statistically significant difference in Coma measured by VAO or OPD-Scan Ⅲ for pupil diameters ranging from 4 to 6 mm(P>0.05), while a statistically significant difference was observed in whole-eye tHOA of other pupil diameters(all P<0.05). The agreement of aberration measurements for each order between VAO and OPD-Scan Ⅲ for 3 mm pupil diameters, SA at 4 and 5 mm pupil diameter and Coma at 4 mm pupil diameter showed a 95% limit of agreement(LoA)<0.1, indicating good agreement; however, poor agreement was found for the remaining aberration measurements at different pupil diameters, with a 95%LoA>0.1, and there were significant differences in higher-order aberrations measured by two devices under a pupil diameter of 3 mm(r=0.218-0.317, P<0.01), 4 mm(r=0.406-0.672, P<0.01), 5 mm(r=0.538-0.839, P<0.01 and r=0.030-0.109, P>0.01)and 6 mm(r=0.369-0.766, P<0.01).CONCLUSION: The VAO demonstrates favorable repeatability when assessing whole-eye higher order aberration under pupil diameters of 3-6 mm. However, there is inadequate agreement and interchangeability in whole-eye higher order aberration at 3-6 mm pupil diameter between VAO and OPD-Scan Ⅲ for clinical purposes.