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.

Laboratory animals serve as the cornerstone in life science research, acting as surrogate models for human physiology, pathology, and disease treatment. They play an irreplaceable role in basic research, drug development, and translational medicine. Gut microbiota, a complex microbial community comprising bacteria, fungi, viruses, and unicellular organisms, colonizes the host's intestinal tract and is closely associated with the maintenance of normal physiological metabolism and overall health. Studies have shown that dysbiosis of the gut microbiota can lead to various diseases, including obesity, diabetes, hypertension, inflammatory bowel disease, and Alzheimer's disease. Therefore, conducting characteristic analyses of the gut microbial composition of laboratory animals can not only enhance the reliability of experimental outcomes but also facilitate their translational application. Sex differences represent a critical variable in biological research, significantly influencing the physiological functions, metabolic traits, and gut microbial composition of laboratory animals. However, a pronounced sex bias has been widely observed in many biological studies, thereby limiting the generalizability of results. This study focused on ten commonly used laboratory animals in life sciences, including mice, rats, guinea pigs, hamsters, rabbits, dogs, cats, non-human primates, miniature pigs, and chickens. Their gut microbial composition was summarized and related sex-specific differences of certain species were analyzed. Furthermore, by comparing the gut microbiota of laboratory animals with that of humans, this study offers novel perspectives for comparative medical research. In summary, this study not only deepens researchers' understanding of gut microbiota characteristics and sex-dependent variations across laboratory animal species but also provides practical guidance for selecting appropriate laboratory animals, constructing sex-specific disease models, and interpreting experimental results in scientific studies.

Laboratory animals serve as the cornerstone in life science research, acting as surrogate models for human physiology, pathology, and disease treatment. They play an irreplaceable role in basic research, drug development, and translational medicine. Gut microbiota, a complex microbial community comprising bacteria, fungi, viruses, and unicellular organisms, colonizes the host's intestinal tract and is closely associated with the maintenance of normal physiological metabolism and overall health. Studies have shown that dysbiosis of the gut microbiota can lead to various diseases, including obesity, diabetes, hypertension, inflammatory bowel disease, and Alzheimer's disease. Therefore, conducting characteristic analyses of the gut microbial composition of laboratory animals can not only enhance the reliability of experimental outcomes but also facilitate their translational application. Sex differences represent a critical variable in biological research, significantly influencing the physiological functions, metabolic traits, and gut microbial composition of laboratory animals. However, a pronounced sex bias has been widely observed in many biological studies, thereby limiting the generalizability of results. This study focused on ten commonly used laboratory animals in life sciences, including mice, rats, guinea pigs, hamsters, rabbits, dogs, cats, non-human primates, miniature pigs, and chickens. Their gut microbial composition was summarized and related sex-specific differences of certain species were analyzed. Furthermore, by comparing the gut microbiota of laboratory animals with that of humans, this study offers novel perspectives for comparative medical research. In summary, this study not only deepens researchers' understanding of gut microbiota characteristics and sex-dependent variations across laboratory animal species but also provides practical guidance for selecting appropriate laboratory animals, constructing sex-specific disease models, and interpreting experimental results in scientific studies.

Objective:To investigate the preventive and therapeutic effects of compound wild chrysanthemum eye pad on blue light-induced alteration of meibomian gland function in mice and its mechanism.Methods:Sixty-four 15-week-old male C57BL/6J mice were divided into two groups of 32 mice each according to random numbers for the prevention test and the treatment test.The respective 32 mice in the prevention and treatment experiments were randomly divided into normal group, blue light group, solvent group and eye pad group according to random numbers, with eight mice in each group, respectively.In the prevention experiments, mice in each group were exposed to blue light at a wavelength of 460 nm and a light intensity of 2 000 lx for 6 hours per day for 15 consecutive days to establish a mouse model of meibomian gland function changes except for the normal group.The solvent group and the eye pad group were treated with the corresponding eye pad before and after the blue light exposure for 25 minutes daily for the 15 consecutive days.The blue light group was treated with blue light exposure only for 15 days, and the mice were photographed at the edge of the meibomian gland on day 15 to observe the function of the meibomian gland except for the normal group.In the treatment test, all groups of mice except the normal group were induced the altered function of the mouse meibomian gland by the above method.The solvent and eye pad groups were treated with corresponding eye pads for 25 minutes in the morning and afternoon of each day for 15 consecutive days after blue light exposure.The blue light group was kept in a standard environment for 15 days and the changes in meibomian gland function of mice were detected by meibomian gland photographs on day 15.Photography of the eyelid margin in vitro, oil red O staining, and hematoxylin-eosin staining were performed to observe the histologic changes in the meibomian glands of mice after the preventive and experimental treatment.The relative expression of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) mRNA in mouse meibomian gland tissues was detected by real-time fluorescence quantitative PCR.The expression of nuclear factor-κB (NF-κB) and phosphorylation of NF-κB (p-NF-κB) proteins in mice meibomian gland tissues was detected by Western blot to assess the degree of amelioration of blue light-induced inflammation in mouse meibomian glands by the compound wild chrysanthemum eye pad.This study was conducted in accordance with the Statement of the Association for Research in Vision and Ophthalmology on the Use of Animals in Ophthalmology and Vision Research, and was approved by the Animal Ethics Committee of Xiamen University (No.XMULAC20220258). Results:Compared with the normal group, a gradually increased number of blocked meibomian gland openings, and a gradually decreased remaining area of lower meibomian gland, were observed in the mice after 15 days of blue light group, and all the differences were statistically different (all at P<0.05). In the prevention test, the number of obstructed opening in the eye pad group was 1.833±0.753, which was significantly less than 3.667±1.033 in the solvent group ( P<0.05). The relative remaining area of the lower lid meibomian gland in the eye pad group was 0.718±0.091, which was significantly greater than 0.624±0.130 in the solvent group ( P<0.05). Hematoxylin-eosin staining showed inflammatory cell infiltration in mouse meibomian gland in the blue light and solvent groups.There was no inflammatory cell infiltration in eye pad group, and the morphology of the acini was similar to that of the normal group.Oil red O staining showed that there was no significant lipid deposition in the groups.The relative expressions of IL-1β, IL-6, TNF-α, and IFN-γ mRNA were significantly lower, and the relative expressions of NF-κB and p-NF-κB proteins were significantly lower in the eye pad group than in the solvent group, showing statistically significant differences (all at P<0.05). In the treatment test, the number of obstructed openings in the eye pad group and solvent group was 4.333±1.211 and 4.833±1.722, respectively, and the relative remaining area of the lower meibomian gland was 0.572±0.151 and 0.588±0.154, respectively, showing no statistically significant differences (both at P>0.05). Hematoxylin-eosin staining showed inflammatory cell infiltration in mouse meibomian glands in the blue light and solvent groups, with a similar morphology of acini as in the normal group.There was no inflammatory cell infiltration in eye pad group.Oil red O staining showed that there was no significant lipid deposition in the groups.The relative expressions of IL-1β, IL-6, and IFN-γ mRNA were significantly lower and the relative expressions of NF-κB and p-NF-κB proteins were significantly lower in the eye pad group than in the solvent group (all at P<0.05). Conclusions:Compound wild chrysanthemum eye pad may have preventive and therapeutic effects on blue light-induced changes in meibomian gland function by reducing the inflammatory response of meibomian gland tissue through the inhibition of the NF-κB signaling pathway.

Objective To discuss the clinical application of coronary CT angiography(CCTA)-derived fractional flow reserve(CT-FFR)in evaluating the risk stratification of the coronary artery stenosis and atherosclerotic plaque quantitative parameters.Methods A total of 122 patients,who received CCTA examination at the Xuzhou Municipal Central Hospital of China,were enrolled in this study.The patients were divided into non-ischemia group(CT-FFR＞0.8,n=66)and ischemia group(CT-FFR0.8,n=56).The characteristics of atherosclerotic plaque were compared between the two groups.Logistic regression analysis was used to analyze the correlation between plaque characteristics and ischemic lesions.Results There were 218 vessels having a CT-FFR＞0.8 and 174 vessels having a CT-FFR ≤0.8.Statistically significant differences in the total plaque volume,calcified plaque volume,plaque length,and stenosis ratio＞50％existed between the two groups(all P＜0.05).Logistic regression analysis indicated that the total plaque volume,calcified plaque volume,plaque length,and stenosis ratio＞50％were the risk factors for myocardial ischemia.Conclusion CT-FFR can be used for the risk stratification of coronary stenosis and atherosclerotic plaque characteristics,which can evaluate the local myocardial blood supply condition from the anatomical stenosis and functional level so as to optimize the diagnosis and treatment measures.

Objective To evaluate the efficacy and safety of white-browed venom hemocoagulase for injection in surgical tresis vulnus.Methods Wanfang,VIP,and CNKI were computerized searched to collect randomized controlled trials(RCTs)of white-browed snake venom thrombin for hemostasis in surgical incisions from the construction of databases to December 1,2023.Meta-analysis was performed using RevMan 5.4 software.Results A total of 13 RCTs with 1 027 patients were included.Meta-analysis showed that the mean hemostasis time,bleeding per unit area,intraoperative bleeding,and thrombin time(TT)on the first postoperative day in the white-browed snake venom hemocoagulase group were smaller than those in the control group(P<0.05);the activated partial thromboplastin time(APTT),prothrombin time(PT),and fibrinogen(FIB)content between the two groups were not statistically significant(P>0.05).Subgroup analysis showed that among different types of surgical incisions,the hemostasis time,bleeding per unit area and intraoperative bleeding were reduced in the white-browed snake venom hemocoagulase group(P<0.05).PT in the white-brow snake venom hemocoagulase group was greater than that in the control group on the first postoperative day of neurosurgical incisions(P<0.05),and the differences in TT,APTT,and FIB between the two groups were not statistically significant(P>0.05);in the first postoperative day of nasal endoscopic surgery and general surgical incisions,there were no statistically significant differences between the two groups in terms of TT,APTT,PT,and FIB(P>0.05);and in the first postoperative day of gynecological incisions,the TT and PT of the white-browed snake venom hemocoagulase group were lower than those of the control group(P<0.05),and the differences in APTT and FIB between the two groups were not statistically significant(P>0.05).A total of six studies reported adverse reactions after the use of white-browed snake venom hemocoagulase,of which four studies did not observe any adverse reactions.Conclusion Compared with the control group,white-browed snake venom hemocoagulase has better hemostatic efficacy for surgical incisions,and has less effect on the coagulation function of patients,without increasing the occurrence of adverse events,and has a better safety profile.

Specific tumor-targeted gene delivery remains an unsolved therapeutic issue due to aberrant vascularization in tumor microenvironment (TME). Some bacteria exhibit spontaneous chemotaxis toward the anaerobic and immune-suppressive TME, which makes them ideal natural vehicles for cancer gene therapy. Here, we conjugated ZIF-8 metal-organic frameworks encapsulating eukaryotic murine interleukin 2 (Il2) expression plasmid onto the surface of VNP20009, an attenuated Salmonella typhimurium strain with well-documented anti-cancer activity, and constructed a TME-targeted Il2 delivery system named Il2/ZIF-8@Salmonella. Both in vitro and in vivo experiments demonstrated that Il2/ZIF-8@Salmonella maintained the tumor-targeting feature of bacteria, and could be effectively phagocytosed by intratumoral macrophages, thus leading to the expression and secretion of IL2 in TME. The detailed analysis of tumor immune microenvironment (TIME) showed that one dose of combinatorial Il2/ZIF-8@Salmonella achieved synergistic actions on a potent remodeling of TIME, marked by the activation of cytotoxic T cells and M1-polarization of macrophages in TME, thus leading to significant anti-tumor effects in melanoma, orthotopic hepatocellular carcinoma, and pulmonary metastasis models. More importantly, Il2/ZIF-8@Salmonella exhibited high safety to major organs and hematopoietic systems. Taken together, we report a novel plasmid/ZIF-8@Salmonella system that simultaneously achieves effective TME-targeted delivery of therapeutic gene, as well as synergistic re-activation of TIME.

OBJECTIVE To systematically evaluate the difference of efficacy and safety of four kinds of commonly used haemocoagulases combined with proton pump inhibitor （PPI） for nonvariceal upper gastrointestinal bleeding （NVUGIB）， and to provide evidence-based basis for clinical decision-making. METHODS Retrieved from PubMed， Web of Science， Wanfang data， VIP and CNKI databases， randomized controlled trials （RCTs） or cohort studies about Hemocoagulase agkistrodon blomhoffii， Haemocoagulase agkistrodon， hemocoagulase and Hemocoagulase bothrops atrox combined with PPI were collected during the inception to Dec. 2021. Two researchers independently screened the literature， extracted data and evaluated the quality of included studies. ADDIS 1.16.8 software was used to conduct a Bayesian network meta-analysis. RESULTS A total of 33 studies were included， involving 3 602 patients. Results of network meta-analysis showed that： in terms of hemostatic efficacy， compared with PPI monotherapy， four kinds of haemocoagulases combined with PPI could significantly improve the hemostatic efficacy of patients （P＜0.05）； there was no statistical significance in the pairwise comparison of different hemocoagulases （P＞0.05）. The optimal probabilistic ranking of network meta-analysis was as follows： Hemocoagulase agkistrodon blomhoffii combined with PPI＞ Hemocoagulase bothrops atrox combined with PPI＞Haemocoagulase agkistrodon combined with PPI＞hemocoagulase combined with PPI＞PPI alone. In terms of the incidence of adverse drug reactions （ADR）， compared with PPI monotherapy， there was no statistical difference in the incidence of ADR among four kinds of haemocoagulases combined with PPI （P＞0.05）. There was no statistical significance in the pairwise 88325750。E-mail：fengyufei@126.com comparison of different hemocoagulases （P＞0.05）. The optimal probabilistic ranking of network meta-analysis was as follows： hemocoagulase combined with PPI＞Hemocoagulase bothrops atrox combined with PPI＞Hemocoagulase agkistrodon blomhoffii combined with PPI＞Haemocoagulase agkistrodon combined with PPI＞PPI alone. CONCLUSIONS Compared with PPI monotherapy， four different sources of hemocoagulases combined with PPI have better efficacy and similar safety in the treatment of NVUGIB. There is no significant difference in efficacy and safety among different hemocoagulases.

Objective:To explore the value of jellyfish sign, an abnormal ultrasonographic sign, in predicting adverse perinatal outcomes of women with complete placenta previa combined with placenta accreta spectrum disorders (PAS).Methods:This retrospective study analyzed the ultrasound images of 72 singleton gravidas, diagnosed with complete placenta previa combined with PAS, who underwent cesarean section at the First Affiliated Hospital of Nanjing Medical University between January 2020 and February 2023. Based on the presence and absence of the jellyfish sign in ultrasound images, these gravidas were divided into the jellyfish-sign group (15 cases, 20.8%) and the non-jellyfish-sign group (57 cases, 79.2%). The clinical data and perinatal outcomes of the two groups were analyzed. The adverse perinatal outcomes encompassed conditions such as abdominal aorta balloon block, uterine artery embolism, hysterectomy, postpartum hemorrhage, and neonatal intensive care unit (NICU) admission of their neonates. Statistical analysis was performed using two independent samples t-test, the Mann-Whitney U test and the Chi-square (or Fisher's exact) test. Results:(1) The jellyfish-sign group exhibited a higher parity [(1.6±0.7) times vs (1.2±0.6) times, t=2.01] and higher prenatal scores of placenta accreta [(12.3±1.5) scores vs (8.6±2.9) scores, t=6.59] than those in the non-jellyfish-sign group (both P<0.05). Among the 57 cases in the non-jellyfish-sign group, there were 14 cases of placenta creta (24.6%), 40 cases of placenta increta (70.2%), and three cases of placenta percreta (5.3%). Among the 15 cases in the jellyfish-sign group, nine cases were diagnosed with placenta increta, six with placenta percreta, and none with placenta creta. The difference in distribution between the two groups was statistically significant (Fisher's exact test, P<0.001). (2) Intraoperative blood loss [(for those who accepted abdominal aorta balloon block, 1 973±1 057) ml vs (1 211±576) ml, t=2.55], red blood cells transfused [4.0 U (2.0-23.0 U) vs 2.5 U (0.0-11.0 U), Z=－2.53], postoperative hospitalization time [(9.7±2.4) vs (7.5±2.2) d, t=3.36], the incidence of abdominal aorta balloon block [15/15 vs 38.6% (22/57), χ2=17.92], uterine artery embolism [for those who accepted abdominal aorta balloon block, 3/15 vs 1.8% (1/57), Fisher's exact test], and requiring blood transfusion [15/15 vs 63.2% (36/57), Fisher's exact test] were higher in the jellyfish-sign group than those in the non-jellyfish-sign group. However, the non-jellyfish-sign group had lower gestational age at delivery [(33.6±1.5) weeks vs (35.2±1.8) weeks, t=－3.24], and lower neonatal Apgar score at 1 min and 5 min [1 min: 8 scores (3-10 scores) vs 9 scores (4-10 scores), Z=－2.46; 5 min: 9 scores (7-10 scores) vs 10 scores (6-10 scores), Z=－2.02] (all P<0.05). There were no significant differences in emergency surgery rate, 24 h postoperative blood loss, neonatal birth weight, and proportion of NICU admission between the two groups. Additionally, no cases of hysterectomy or death were observed in the two groups. Conclusions:Ultrasound examination revealing jellyfish signs in patients with complete placenta previa and PAS is associated with an increased likelihood of adverse perinatal outcomes. Consequently, the management of these patients should be given greater attention.