1.Key Challenges and Mitigation Strategies for Animal Pregnancy in Non-clinical Reproductive Toxicity Testing of Drugs
Kun LIU ; Qing LAN ; Bing YI ; Xiaojie XIE
Laboratory Animal and Comparative Medicine 2025;45(4):449-456
Non-clinical reproductive toxicity studies typically employ mammals like rats, rabbits, and cynomolgus monkeys, with animal pregnancy being a key challenge in such testing. This article focuses on the difficulties encountered in the animal pregnancy process and potential countermeasures. Rats can be used for fertility and early embryonic development toxicity studies (Segment Ⅰ), embryo-fetal development toxicity studies (Segment Ⅱ), and perinatal toxicity studies (Segment Ⅲ). The estrous cycle of female rats can be determined by vaginal smear, and mating behavior is confirmed through copulatory plug checks the following day after pairing one female with one male in the same cage. Rabbits are commonly used in embryo-fetal development toxicity studies (Segment Ⅱ). Mating behavior between male rabbits and estrous females is observed to determine the time of conception. However, challenges such as atypical estrus of female rabbits, large variations in estrus between batches, and mating failure often occur in reproductive toxicity testing, which may be addressed through prolonged light exposure, increased protein supplementation, optimized mating strategies, and environmental modifications like female and male rabbits are raised adjacent to each other. Non-human primates (NHPs) are typically employed in perinatal toxicity studies (Segment Ⅲ), where one of the key challenges lies in accurately determining sexual maturity in males - a critical factor for reproductive toxicity testing, which can be assessed through comprehensive evaluation of age, body weight, and testicular volume. Generally, male macaques are considered sexually mature when they meet the following criteria: age >4.5 years, body weight >4.5 kg, single testis volume >10 mL, and combined testicular volume >20 mL. For pregnancy confirmation, ultrasound examination demonstrating visible gestational sacs is required, though this necessitates experienced veterinary clinicians to establish standardized ultrasound examination protocols. In conclusion, reproductive toxicity studies should employ species-appropriate detection methods and evaluation criteria based on anatomical characteristics of the reproductive system to ensure successful mating and proper study execution.
2.Effect of cardiac shock wave therapy on electrocardiogram and myocardial perfusion in coronary artery disease patients
Chun-Mei TIAN ; Jing-Jing ZHENG ; Na JIA ; Lin ZHANG ; Bao-Yi LIU ; Jun-Meng LIU ; Ming LAN ; Bing LIU
Chinese Journal of Interventional Cardiology 2024;32(6):317-323
Objective To explore the effect of cardiac shock wave therapy(CSWT)on ST deviation of electrocardiogram and myocardial perfusion imaging in coronary artery disease(CAD)patients.Methods CAD patients who received CSWT in Cardiology Department of Beijing Hospital from December 2016 to August 2022 were enrolled.Three months of CSWT were conducted with a total of 9 times shock wave treatment.Clinical data,myocardial perfusion imaging data and stress electrocardiogram data were collected.Myocardial perfusion score,electrocardiographic data were compared before and after CSWT.Results A total of 55 patients were finally enrolled.There were 43 male and 12 female patients with an average age of(67.45±8.96)years old.ST deviation on 12 leads of electrocardiogram did not show significant difference before and after CSWT.Myocardial perfusion imaging showed global stress perfusion score(P=0.031)and reverse perfusion score(P=0.024).Global rest ischemia score reduced after CSWT(P=0.034).Target stress perfusion score(P=0.002),target reverse perfusion score(P=0.002),target reverse ischemic area(P=0.001)were improved after CSWT.Conclusions CSWT may not influence ST deviation of electrocardiogram,but may improve myocardial ischemia in CAD patients,
3.Simulation study of musculoskeletal system of lower limbs based on synergistic effects of stress and electromagnetic fields
Ruo-Bing LIU ; Qi-Lin PEI ; Xi SHAO ; Dan WANG ; Yu-Lan TIAN ; Ze-Dong YAN ; Da JING
Chinese Medical Equipment Journal 2024;45(9):21-26
Objective To apply a COMSOL-based finite element analysis method to investigating the electric field effects produced by the human lower limb musculoskeletal system under the synergistic effects of stress field and electromagnetic field.Methods Firstly,a 3D human body model was constructed by Maxon Cinema 4D R21 software,and then imported into COMSOL 6.1 software in STL format.Secondly,an electromagnetic field intervention and stress loading model for the left lower limb of the human body was designed and constructed,in which 15 Hz quasi-pulse group current signals were used for electromagnetic field excitation and the stress field was realized by applying a vibration load with an average compressive force of about 90 N/cm2 to the left foot of the human body.Finally,the electromagnetic properties of human tissue were simulated by numerical simulation,and then the effects of stress field or elecromagnetic field or combined stress field and electromagnetic field on human bioelectric field were compared.Results Simulation results showed that the electric field intensity peaked at the leg joints under both electromagnetic and stress fields acting alone or synergistically,the bioelectric field intensity generated by the human body was related to the distance from the exogenous excitation loading location,and the electric field generated under synergistic action was equivalent to the linear superposition of the bioelectric field in the tissue induced by the electromagnetic field and the stress field acting alone.Conclusion Data supplement is provided for predicting bioelectric field changes within the musculoskeletal tissue,and theoretical foundation is laid for the development and application of multi-physics field synergistic intervention therapy for treating the disorders of the lower limb musculos-keletal system.[Chinese Medical Equipment Journal,2024,45(9):21-26]
4.Dynamic changes and function of mitochondria in development of em-bryonic hematopoietic stem cells
Rong ZHANG ; Haixin ZHAO ; Jie ZHOU ; Di LIU ; Yu LAN ; Bing LIU
Chinese Journal of Pathophysiology 2024;40(5):769-776
AIM:To describe the dynamic characteristics of mitochondria in the development of mouse embryonic hematopoietic stem cells,and to explore the function of mitochondria in this process.METHODS:Single-cell transcrip-tomic data of continuous developmental hematopoietic stem cell-related populations were analyzed to describe the dynamic changes of genes related to mitochondrial synthesis and energy metabolism.To explore the dynamic changes in the number and activity of mitochondria during the development of hematopoietic stem cells,we detected the mitochondrial number and mitochondrial membrane potential of the cells in each stage of hematopoietic stem cell development by fluorescent probe staining combined with flow cytometry.We added small molecule inhibitors of mitochondrial synthesis and energy metabolism and used hematopoietic cell colony formation assay to detect the effect of mitochondrial function inhibition on the induction of hematopoietic products in vitro.RESULTS:(1)Single-cell transcriptome analysis showed that genes in-volved in mitochondrial synthesis and oxidative phosphorylation were significantly up-regulated in endothelial cell and type Ⅰ pre-hematopoietic stem cell compared with those involved in glycolysis,and these genes could significantly distinguish continuous dynamic populations.(2)The results of fluorescence staining and flow cytometry analysis showed that mito-chondrial number and mitochondrial membrane potential had an increasing trend during the continuous development of he-matopoietic stem cell,reaching the highest level in the precursor stage of type 2 pre-hematopoietic stem cell,and decreasing in the mature hematopoietic stem cell of fetal liver.(3)Compared with control group,inhibition of mitochondrial respirato-ry chain Ⅰ and Ⅴ significantly reduced the number of hematopoietic colonies(P<0.05).CONCLUSION:(1)Genes re-lated to mitochondrial synthesis and oxidative phosphorylation are highly expressed in hemogenic endothelial cells and type Ⅰpre-hematopoietic stem cells,and can be used to distinguish continuous developing populations.(2)The mitochondrial number and mitochondrial membrane potential increased continuously during hematopoietic stem cell development and reached the highest level in type 2 pre-hematopoietic stem cells.(3)Inhibition of mitochondrial respiratory chain Ⅰ and Ⅴ significantly reduced the production of hematopoietic products in vitro.
5.Dynamic ultrasound evaluation of regeneration of semitendinosus and gracilis tendon after graft harvest for anterior cruciate ligament reconstruction
Bing ZHANG ; Xiaoli HUANG ; Hongyu ZHENG ; Huihui YANG ; Bei LAN ; Wan CAO ; Silin LIAO
Chinese Journal of Ultrasonography 2024;33(11):947-953
Objective:To evaluate the regeneration and biomechanical property recovery of semitendinosus tendon(ST)/gracilis tendon(GT) after anterior cruciate ligament(ACL) reconstruction using shear wave elastorgraphy (SWE) combined with high-frequency ultrasound(HFUS).Methods:Twenty-five patients who underwent ST/GT autograft reconstruction after ACL rupture at the People′s Hospital of Guangxi Zhuang Autonomous Region from January 2020 to June 2022 were prospectively enrolled. All patients underwent HFUS, SWE and flexion strength assessment at pre-operation and 1, 3, 6, 12, 24 months postoperatively. The morphology, length, cross-sectional area and SWE of ST/GT and flexion strength of knee were recorded at each time point. Repeated measures analysis of variance was employed to compare the cross-sectional area and elasticity value of regenerated ST/GT at different time points. Spearman correlation analysis was used to investigate the relationship between the elasticity value of regenerated ST/GT and flexion strength.Results:The regeneration rates of ST/GT after being harvested for ACL reconstruction were 88% and 92%. The length of the regenerated ST/GT were shorter than before operation(both P<0.05). Repeated measures analysis of variance revealed significant differences in the cross-sectional area of regenerated ST/GT, both in terms of time effect and inter-group effect ( F=27.264, 28.980; both P<0.001), but no significant difference was observed in the interaction effect ( F=0.670, P=0.652). The cross-sectional area of regenerated ST/GT was the largest at 3 months postoperatively ( P<0.05), and restored to the preoperative level at 12 and 24 months postoperatively (both P>0.05). Repeated measures analysis of variance showed that the elasticity values of the regenerated ST/GT were significantly different in terms of time effect, group effect, and interaction effect ( F=265.402, 33.015, 11.475; all P<0.001). The elasticity of regenerated ST/GT post-operation gradually increased over time. The flexion strength level of knee gradually improved post-operation(χ 2=34.83, P<0.001). The elasticity values of the regenerated ST and GT showed significant positive correlations with the flexion strength ( rs=0.755, 0.761; both P<0.001). Conclusions:HFUS discovers that most of ST/GT can be regenerated after being harvested for ACL reconstruction. The flexion strength and elasticity value of regenerated tendon recover gradually with time. It is suggested that the SWE can predict the recovery of biomechanical property of regenerated ST/GT.
6.Clinical Observation on the Joint Needling Method Combined with Ultrasound in the Treatment of Patellofemoral Pain Syndrome of Qi Stagnation and Blood Stasis Type
Xiu-Lan LI ; Hui-Kang YUAN ; Shu-Xiong LUO ; Long-An CHEN ; Ai-Guo XUE ; Yu-Bing LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):141-146
Objective To observe the clinical efficacy of joint needling method combined with ultrasound in the treatment of qi stagnation and blood stasis type of patellofemoral pain syndrome(PFPS).Methods Eighty-six patients with qi stagnation and blood stasis type of PFPS were randomly divided into observation group and control group,with 43 cases in each group.The control group was given western medicine conventional treatment combined with functional exercise,and the observation group was given joint needling method combined with ultrasound treatment on the basis of the control group.Both groups were treated for 2 consecutive weeks.After 2 weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Visual Analogue Scale(VAS)scores of knee pain and the Kujala scale scores of the two groups were observed before and after treatment.The changes in active range of motion(AROM)of the affected knee joint were compared before and after treatment between the two groups.Results(1)After treatment,the VAS scores of the two groups of patients were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving the level of VAS scores,and the difference was statistically significant(P<0.05).(2)After treatment,the Kujala scores of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving the level of Kujala scores,and the difference was statistically significant(P<0.05).(3)After treatment,the AROM of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving the level of AROM,and the difference was statistically significant(P<0.05).(4)The total effective rate was 95.35%(41/43)in the observation group and 81.40%(35/43)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P<0.05).Conclusion The joint needling method combined with ultrasound can significantly relieve the pain symptoms of patients with PFPS and promote the recovery of knee joint function,and the clinical efficacy is remarkable.
7.Implementation of surveillance,prevention and control of healthcare-asso-ciated infection in maternal and child healthcare institutions:A nation-wide investigation report
Shuo LI ; Xi YAO ; Hui-Xue JIA ; Wei-Guang LI ; Xun HUANG ; Shu-Mei SUN ; Xi CHENG ; Qing-Lan MENG ; Xiang ZHANG ; Jing-Ping ZHANG ; Ya-Wei XING ; Qing-Qing JIANG ; Lian-Xuan WU ; Bing-Li ZHANG ; Xiao-Jing LIU ; Liu-Yi LI
Chinese Journal of Infection Control 2024;23(3):323-329
Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24%of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66%,85.96%,80.77%,and 74.19%,respectively.51.22%MCH institutions adopted information surveillance system on HAI cases.94.31%MCH institutions carried out surveillance on hand hygiene compliance.Over 90%MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54%MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90%MCH insti-tutions established three-level pre-examination triage systems.86.18%set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50%.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.
8.Research status of the role of remimazolam in improving cognitive function during perioperative period
Jin-Xin LAN ; Sen LI ; Duo YANG ; Jun-Bing HE ; Long-Sheng ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):773-777
Postoperative cognitive dysfunction(POCD)is one of the common complications in the perioperative period,and it has a high incidence in elderly patients,and the large production of neuroinflammatory factors under surgical stimulation is the main cause of postoperative POCD.As an ultra-short-acting benzodiazepine of γ-aminobutyric acid receptor agonist,remimazolam can play a sedative-hypnotic and anxiolytic role in clinical practice,and can reduce inflammatory factors in the central nervous system and improve postoperative cognitive dysfunction by inhibiting neuroinflammatory response and oxidative stress.This article reviews the protective effect and mechanism of remimazolam on postoperative cognitive function,so as to provide a basis for the clinical use of remimazolam.
9.Application of Functionalized Liposomes in The Delivery of Natural Products
Cheng-Yun WANG ; Xin-Yue LAN ; Jia-Xuan GU ; Xin-Ru GAO ; Long-Jiao ZHU ; Jun LI ; Bing FANG ; Wen-Tao XU ; Hong-Tao TIAN
Progress in Biochemistry and Biophysics 2024;51(11):2947-2959
Plant natural products have a wide range of pharmacological properties, not only can they be used as plant dietary supplements to meet the nutritional needs of the human body in the accelerated pace of life, but also occupy an important position in the research and development of therapeutic drugs for the treatment of tumors, inflammation and other diseases, and have been widely accepted by the public due to their good safety. However, despite the above advantages of plant natural products, limiting factors such as low solubility, poor stability, lack of targeting, high toxicity and side effects, and unacceptable odor have greatly impeded their conversion to clinical applications. Therefore, the development of new avenues for the application of new natural products has become an urgent problem to be solved at present. In recent years, with the continuous development of research, various strategies have been developed to improve the bioavailability of natural products. Among them, nanocarrier delivery system is one of the most attractive strategies at present. In past studies, a large number of nanomaterials (organic, inorganic, etc.) have been developed to encapsulate plant-derived natural products for their efficient delivery to specific organs and cells. Up to now, nanotechnology has not only been limited to pharmaceutical applications, but is also competing in the fields of nanofood processing technology and nanoemulsions. Among the various nanocarriers, liposomes are the largest nanocarriers with the largest market share at present. Liposomes are bilayer nanovesicles synthesized from amphiphilic substances, which have advantages such as high drug loading capacity and stability. Attractively, the flexible surface of liposomes can be modified with various functional elements. Functionalized modification of liposomes with different functional elements such as antibodies, nucleic acids, peptides, and stimuli-responsive moieties can bring out the excellent drug delivery function of liposomes to a greater extent. For example, the modification of functional elements with targeting function such as nucleic acids and antibodies on the surface of liposomes can deliver natural products to the target location and improve the bioavailability of drugs; the modification of stimulus-responsive groups such as photosensitizers, magnetic nanoparticles, pH-responsive groups, and temperature sensitizers on the surface of liposomes can achieve controlled release of drugs, localized targeting, and synergistic thermotherapy. In addition to the above properties, by using functionalized liposomes to encapsulate natural products with irritating properties can also effectively mask the irritating properties of natural products, improve public acceptance, and increase the possibility of application of irritating natural products. There are various strategies for modifying liposomes with functional elements, and the properties of functionalized liposomes constructed by different construction strategies differ. The commonly used construction strategies for functionalized liposomes include covalent modification and non-covalent modification. These two types of construction strategies have their own advantages and disadvantages. Covalent modification has better stability than non-covalent modification, but its operation is cumbersome. With the above background, this review focuses on the three typical problems faced by plant natural products at present, and summarizes the specific applications of functionalized liposomes in them. In addition, this paper summarizes the construction strategies for building different types of functionalized liposomes. Finally, this paper will also review the opportunities and challenges faced by functionalized liposomes to enter clinical therapy, and explore the opportunities to overcome these problems, with a view to better realizing the precise control of plant nanomedicines, and providing ideas and inspirations for researchers in related fields as well as relevant industrial staff.
10.Posttraumatic growth status and latent profile analysis of nurses at psychiatric department
Li ZENG ; Jialin WANG ; Zhongqing YUAN ; Bing CAO ; Fengxue YANG ; Guiling LIU ; Lan LI
China Occupational Medicine 2024;51(4):399-404
Objective To explore the current status of posttraumatic growth (PTG) among nurses at psychiatric department and analyze its latent profiles and population characteristics. Methods A total of 357 nurses from psychiatric departments of five tertiary Grade A hospitals were selected as the research subjects using the convenience sampling method. The PTG and professional quality of life were studied using the Posttraumatic Growth Inventory and the Chinese version of the Compassion Fatigue Scale. Results The PTG score of the nurses was (56.6±23.2). The scores of compassion satisfaction, burnout, and secondary traumatic stress among nurses were (32.6±7.2), (26.9±5.9), and (26.0±5.4), respectively. The result of potential profile analysis showed that the nurses could be divided into three latent profiles based on PTG levels: low PTG group (34.4%), moderate PTG group (44.0%), and high PTG group (21.6%). The results of multinomial logistic regression analysis showed that the nurses who slept 7-8 hours per day were at higher risk of being in the high PTG group compared with those who slept more than eight hours per day (P<0.05). Psychiatric nurses who took regular exercise were at higher risk of being in the high PTG group compared with those who took irregular exercise (P<0.05). The nurses who had high job satisfaction scores were at higher risk of being in the high PTG group compared with those who had low job satisfaction scores (P<0.01). The nurses with higher compassion satisfaction scores increased the risk of being in the high PTG group compared with those with lower compassion satisfaction scores (P<0.01). The nurses with higher burnout scores increased the risk of being in the low PTG group compared with those with lower burnout scores (P<0.01). Conclusion The PTG characteristics of the nurses exhibit heterogeneity and can be categorized into three distinct profiles. Sleep duration, regular exercise, job satisfaction, compassion satisfaction, and burnout are influencing factors for the PTG latent profiles of nurses working at psychiatric department.

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