ObjectiveTo explore the process and guidelines for ethical review in decentralized drug clinical trials， promote clinical trial progress， and ensure drug development progress. MethodsThe key points of the ethical review were summarized by studying the relevant laws and regulations on decentralized drug clinical trials， analyzing the advantages and challenges of decentralized drug clinical trials， and combining the experience of the ethics committee of the institution in reviewing decentralized drug clinical trials. ResultsRelevant laws and regulations were the basis for the ethical review， and the ethics committee should adopt appropriate review methods based on regulations and hospital ethical standard operating procedures. The ethics committee should focus on the feasibility， applicability， and rationality， the adequacy of informed consent， the protection of rights and interests and privacy of subjects， as well as the qualification and standard operating procedures of electronic platforms for conducting decentralized drug clinical trials. ConclusionDecentralized drug clinical trials are in their early stages and urgently require guidance from relevant laws and regulations. Ethical review is also constantly being refined through exploration. It is necessary to supervise the implementation of responsibilities by all parties， pay attention to the rights and interests of subjects， and gradually promote the implementation of decentralized drug clinical trials.

Objective To explore the association between oral microbiota and esophageal carcinogenesis. Methods A case-control study design was employed. A total of 309 subjects were recruited, consisting of 159 healthy controls, 32 cases of esophageal basal cell hyperplasia, 32 cases of low-grade intraepithelial neoplasia, 14 cases of high-grade intraepithelial neoplasia, and 72 cases of esophageal squamous cell carcinoma. Tongue swab samples were collected for 16S rRNA sequencing. The α-diversity and β-diversity of the microbiota were analyzed, and the characteristics of the microbial communities at different stages of esophageal carcinogenesis were compared. The strength of the association was expressed by odds ratio (OR) and 95% confidence interval (CI). Results α-diversity analysis indicated significant differences in the observed species number (Sobs) index across various stages of esophageal cancer progression (P<0.001). After adjusting for confounding factors such as age, gender, smoking, and alcohol consumption, the Simpson index was positively correlated with carcinogenesis (P=0.006). β-diversity analysis revealed differences in microbiota structure among the groups. After ordered multinomial logistic regression analysis and adjustment for multiple confounding factors, the relative abundance of Peptostreptococcus (OR: 2.06, 95%CI: 1.22–3.60), Patescibacteria (OR: 1.31, 95%CI: 1.04–1.67), Capnocytophaga (OR: 1.24, 95%CI: 1.05–1.54), and Bacteroidota (OR: 1.02, 95%CI: 1.00–1.05) was positively correlated with carcinogenesis. The relative abundance of Stomatobaculum (OR: 0.57, 95%CI: 0.30–1.00) and Actinobacteriota (OR: 0.95, 95%CI: 0.92–0.98) was negatively correlated with carcinogenesis. Conclusion Specific oral microbiotas are significantly associated with esophageal carcinogenesis, and synergistic or antagonistic interactions may be observed among the microbiota.

Objective To generate a dense granule protein 3 (GRA3) gene-deficient mutant of the Toxoplasma gondii ME49 strain and to test the virulence of the mutant. Methods Gene-deficient parasites were generated with the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) system. Guide RNA (gRNA) was designed using the E-CRISPR software, and mutated on the pSAG1::Cas9-U6::sgUPRT plasmid using the Q5 site-directed mutagenesis kit to generate the pSAG1::Cas9-U6::sgGRA3 plasmid. A GRA3 donor plasmid containing GRA3 gene upstream sequences, pyrimethamine resistant gene dihydrofolate reductase-thymidylate synthase (DHFR-TS) and GRA3 gene downstream sequence was generated, and GRA3 donor DNA was amplified using PCR assay. The pSAG1::Cas9-U6::sgGRA3 plasmid and GRA3 donor DNA were electroporated into tachyzoites of the wild-type T. gondii ME49 strain. Then, parasite suspensions were inoculated into human foreskin fibroblast (HFF) cells and screened with pyrimethamine to yield pyrimethamine-resistant parasites for monoclonal screening. The GRA3 gene deficient monoclonal strain (ME49Δgra3) of T. gondii was identified using PCR and Western blotting assays, and the expression of GRA3 protein was determined in the T. gondii ME49Δgra3 strain using Western blotting. Subsequently, 1 000 freshly lysed tachyzoites of T. gondii ME49 and ME49Δgra3 strains were transferred to 12-well plates seeded with HFF cells, and incubated at 37 °C containing 5% CO₂ for 7 days, and the number of plaques was counted by staining with crystal violet solutions. HFF cells infected with tachyzoites of T. gondii ME49 and ME49Δgra3 strains were stained using Giemsa solutions, and the numbers of cells containing 1, 2, 4, and > 4 T. gondii parasitophorous vacuoles were counted. In addition, the survival rates of C57BL/6 mice infected with T. gondii ME49 and ME49Δgra3 strains were compared 35 days post-infection. Results PCR assay revealed successful amplification of both the upstream and downstream homologous arm bands of the DHFR-TS gene in the T. gondii ME49Δgra3 strain, and no corresponding bands were amplified in the ME49 strain. The GRA3 band was amplified in the ME49 strain, and the DHFR-TS band, rather than GRA3 band, was amplified in the ME49Δgra3 strain. Western blotting determined absence of GRA3 protein expression in the ME49Δgra3 strain. Crystal violet staining showed that the T. gondii ME49 strain produced more plaques than the ME49Δgra3 strain [(352.67 ± 26.39) plaques vs. (235.00 ± 26.29) plaques; t = 5.472, P < 0.01], and Giemsa staining revealed that the proportion of T. gondii parasitophorous vacuoles containing at least four T. gondii tachyzoites was higher in HFF cells infected with the ME49 strain than in those infected with the T. gondii ME49Δgra3 strain [(75.67 ± 2.52)% vs. (59.67 ± 2.31)%; t = 8.113, P < 0.01], and the proportion of T. gondii parasitophorous vacuoles containing at least 1 or 2 T. gondii tachyzoites was higher in HFF cells infected with the T. gondii ME49 strain than in those infected with the T. gondii ME49Δgra3 strain [(24.33 ± 2.52)% vs. (40.33 ± 2.31)%; t = −8.113, P < 0.01]. In addition, mice infected with the T. gondii ME49 and ME49Δgra3 strains started to die 8 and 9 days post-infection, and the 35-day mortality rates of mice infected with T. gondii ME49 and ME49Δgra3 strains were 10.00% and 70.00% post-infection (χ² = 6.762, P < 0.01). Conclusions The T. gondii ME49Δgra3 strain has been successfully generated, and GRA3 protein may increase the virulence of the T. gondii ME49 strain.

OBJECTIVE To provide reference for the closed-loop management of externally purchased medications for inpatients in medical institutions in Shenzhen， thus improve the overall level of pharmaceutical affairs management in medical institutions in Shenzhen. METHODS The relevant guidelines， expert consensus， thematic reviews and policy documents were conducted using keywords such as “ externally purchased drugs”“externally distributed drugs”“externally purchased prescriptions” “externally distributed prescriptions”“closed-loop management” and their corresponding English terms. The initial draft of the Consensus on Closed-loop Management of Externally Purchased Medications for Inpatients in Shenzhen Medical Institutions （shortened for Consensus） was drafted based on the practical experience of the management of externally purchased drugs in medical institutions in Shenzhen. After two questionnaire surveys and four expert symposiums， the Consensus recommendation opinions were formed. RESULTS & CONCLUSION The Consensus covers 10 aspects， including the definition and usage conditions of externally purchased drugs， management organization and informatization construction， principles for catalogue adjustment， catalogue formulation process， prescription issuance and dispensing， return-to-hospital acceptance process， hospital use process and safety management， home pharmaceutical services， supervision and management， as well as principles for prescription dispensing in retail pharmacies and selection of retail pharmacies. It contributes to the improvement of the management of externally purchased medications in medical institution in Shenzhen.

Objective To clarify the current development status and research hotspots in the field of experimental drug management in China through data mining by bibliometric. Methods Key words such as “experiment”, “drug”, and “management” were used to search the Chinese literature in China National Knowledge Infrastructure （CNKI）. The title, author name, author affiliation, Chinese abstract, Chinese keywords, publication period, journal name, and other content of the literature were extracted from the literature. Cluster analysis was performed by CNKI literature visualization analysis system, CiteSpace and other software, and a network knowledge map was drawn. Results The literature in the field of experimental drug management in China was first published in 1994, and a total of 140 articles were published until 2022. Among them, 20 articles were supported by relevant funds, and the keyword co-occurrence frequency was highest among “subjects”. The most frequently published medium was the Chinese Pharmacological Yearbook. Conclusion At present, the quantity and quality of literature in the field of experimental drug management in China were relatively small, and the cooperation and communication among authors were not close. The funding from various fund projects in this field was also lacking. These factors led to a lower overall development level and slower development speed in this field.

Objective To investigate the entrance surface dose (ESD) of dental radiological diagnosis and treatment devices in Nanping City of Fujian Province, China, assess the radiation risk differences between cone beam computed tomography (CBCT) and conventional oral panoramic tomography (COPT), and compare the output dose levels between domestic and imported devices and between public and private medical institutions, and to provide evidence for optimizing radiation protection strategies. Methods A cross-sectional survey was conducted on 38 extraoral dental X-ray devices from 38 dental institutions in Nanping City. Measurements of ESD for different exposure types (adult/child COPT and CBCT) were performed using an adult head-and-neck phantom and thermoluminescent dosimeters. A statistical analysis (Mann-Whitney U test) was applied to compare dose differences by device type and institution type. Results The median tooth-region doses for adult/child CBCT (8.97/6.80 mGy) were significantly higher than those of adult/child COPT (0.33/0.24 mGy), with the 75th percentile values (12.44/8.18 mGy) exceeding the national guideline level of 7 mGy. Domestically manufactured devices demonstrated higher median doses and greater dose variability compared to imported devices (P < 0.05). Private institutions exhibited inferior dose control stability relative to public institutions (P < 0.001). CBCT delivered substantially higher radiation exposure to the thyroid and ocular lenses, with child lens dose reaching 5.9 times that of COPT. Conclusion Dental CBCT radiation doses in Nanping City exceed the guideline level. Enhanced protection for sensitive organs, restriction of unnecessary pediatric examinations, technological upgrades for domestic devices, and strengthened regulation and operational standardization of private institutions are critical to achieve precise radiation protection and improved medical quality.

Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔ_pMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.

OBJECTIVE: To explore the effect of light music therapy on delirium in intensive care unit (ICU) patients undergoing invasive mechanical ventilation, and provide evidence-based support for clinical prevention of delirium. METHODS: A prospective randomized controlled trial was conducted. 140 patients with invasive mechanical ventilation admitted to the department of respiratory and critical care medicine of First Affiliated Hospital of Guangxi Medical University from January 2024 to January 2025 were enrolled. The patients were divided into intervention group and control group using a random number table method. The control group received routine treatment and nursing care, while the intervention group received light music therapy three times a day for 30 minutes each time for 7 consecutive days. The confusion assessment method-ICU (CAM-ICU) was used to evaluate delirium, and the incidence of delirium within 7 days was statistically analyzed. Richmond agitation-sedation score (RASS), critical care pain observation tool (CPOT) score, mechanical ventilation duration, the length of ICU stay, and ICU stay expenses were record. RESULTS: 129 cases were ultimately included, including 64 cases in the control group and 65 cases in the intervention group. There was no statistically significant difference in baseline data between the two groups, indicating comparability. The incidence of delirium in the intervention group was significantly lower than that in the control group (27.7% vs. 51.6%, χ ² = 7.687, P = 0.006). There was no significantly difference in RASS score between the two groups before enrollment (P = 0.840). After intervention, the RASS score in the intervention group significantly decreased, from 2.00 points on the 1st day of enrollment to 0.00 points on the 7th day, while the control group only decreased from 2.00 points to 1.50 points. The decreasing trend of the intervention group was more pronounced, especially on the 3rd day (P = 0.047) and the 7th day (P =0.005), with significant differences between the groups. The time effect (F = 18.929, P < 0.001), group effect (F = 6.655, P = 0.011), and time group interaction effect (F = 7.372, P < 0.001) of the two groups of RASS score were significant, suggesting that light music therapy has better timeliness and sustainability in improving patients' sedation status. There was no significantly difference in CPOT score between the two groups before enrollment (P = 0.902). After intervention, the CPOT score in the intervention group rapidly decreased from 3.00 points before enrollment to 1.00 points on the 1st day, and continued until the 7th day, while the control group showed a slower decrease from 2.50 points to 2.00 points and only dropped to 1.00 points on the 7th day. There were significant differences on 1st day and 3rd day between two groups (both P < 0.05). The time effect (F = 28.125, P < 0.001), group effect (F = 11.580, P = 0.001), and time group interaction effect (F = 4.048, P = 0.020) of the two groups of CPOT score were significant, indicating that light music therapy has better pain control, but the interaction effect is low, indicating that the impact of the intervention on the CPOT score was mainly concentrated in the early stage (1-3 days), and the long-term effect may be influenced by other factors. Compared with the control group, the intervention group showed a significant reduction in mechanical ventilation time (days: 10.57±2.94 vs. 11.95±3.74, P = 0.021) and the length of ICU stay (days: 14.91±4.37 vs. 17.53±4.83, P = 0.002). The ICU hospitalization expenses of the intervention group was slightly lower than that of the control group [ten thousand yuan: 22.431 (12.473, 28.489) vs. 29.362 (11.996, 41.389)], but the difference was not statistically significant (P = 0.086). CONCLUSIONS Light music therapy can effectively reduce the incidence of delirium in patients undergoing invasive mechanical ventilation, improve consciousness and pain perception, shorten mechanical ventilation time and hospital stay, and has significant clinical promotion value high-quality studies.
Humans ; Delirium/prevention & control* ; Intensive Care Units ; Respiration, Artificial ; Music Therapy ; Prospective Studies ; Male ; Female ; Middle Aged ; Critical Care ; Aged

AIM: To investigate and analyze the current situation and needs of clinical research nurses in China, in order to provide scientific basis for constructing a training system for research nurses, promoting standardized training, and achieving standardized management for them. METHODS:A self-made questionnaire was used to investigate 102 research nurses from nearly 70 well-known clinical trial institutions in China. The contents of the questionnaire mainly included the general information, professional experience and work content of the research nurses, the sense of accomplishment and training needs of clinical trial work. RESULTS: Among the 102 research nurses surveyed, 92.15% have a bachelor's degree or above; 53.92% of those have intermediate or higher professional titles; 74.51% of them are part-time research nurse. Among professional experiences, 19.61% have more than 10 years of clinical trial experience; 47.06%, 40.20%, and 21.17% of surveyed research nurses were authorized to participate in clinical trial drug management, sample management, and quality control; 70.59% of research nurses have a high sense of achievement in their daily work. In terms of education and training needs, clinical trial related laws and regulations, standardized training for clinical trial protocol implementation, and good clinical practice (GCP) are the three most important aspects. CONCLUSION: Clinical research nurses in China have a relatively high level of education and nursing experience, but there is still a large gap in the amount of professional full-time clinical research nurses in China. Due to the rapid development of innovative drugs and devices, as well as the urgent need to improve the clinical research system, it is necessary to establish a training, assessment, and evaluation system for research nurses that is in line with China's national conditions in order to improve the professional level of research nurses, and improve the quantity and quality of clinical trial research on innovative drugs and devices in China.

OBJECTIVE To further standardize the implementation and management standards of pharmaceutical active consultation in medical institutions and provide a reference for providing high-quality pharmaceutical services. METHODS Guided by the Chongqing Pharmaceutical Association and led by the Third Affiliated Hospital of Chongqing Medical University， a panel of experts consisting of pharmaceutical and medical management professionals from multiple medical institutions was established to discuss the basic requirements， service processes， quality control， and evaluation improvement of pharmaceutical active consultation. The drafting team then organized， summarized， analyzed and revised the opinions， and provided feedback to ultimately form a consensus. RESULTS & CONCLUSIONS This consensus provides a detailed exposition of the basic requirements， service processes， quality control， and evaluation improvement of pharmaceutical active consultation， offering standards for the implementation of pharmaceutical active consultation in medical institutions in China， which is of major implications for strengthening the pharmaceutical service capabilities of medical institutions.