1.Protective effects of cinnamaldehyde on benzene-induced immune and oxidative stress injury in mice
Mengyang LI ; Gui WANG ; Yamei QIAO ; Pingyu WANG ; Min JIN ; Dong YANG ; Junwen LI
Military Medical Sciences 2024;48(1):44-51
Objective To investigate the effects of cinnamaldehyde,the main active component of cinnamon,on benzene-induced immune injury in mice and the related mechanism.Methods Forty male BALB/c mice were randomly divided into the control group,model group(benzene 500 mg/kg),cinnamaldehyde low,medium and high dose groups(5,25,50 mg/kg),with 8 mice in each group.Except the control group,mice in each group were treated with benzene by intragastric administration daily to induce immune and oxidative stress damage,but the intervention group was treated with cinnamaldehyde 5 times/week for 3 weeks.After medication,peripheral blood was collected 24 h after the last gavage for blood cell count,and the changes in body weight of mice in each group were observed.The pathological structure of the spleen and thymus was observed via hematoxylin-eosin(HE)staining.Peripheral blood mononuclear cells(PBMCs)of mice were extracted and the amounts of reactive oxygen species(ROS)and ATP in mitochondria were measured.Plasma levels of malondialdehyde(MDA)were measured using the barbituric acid method,the activity of glutathione peroxidase(GSH-PX)in plasmawith the dithiodinitrobenzoic acid methodand the activity of total superoxide dismutase(SOD)in plasma using the hydroxylamine method.Results After exposure to benzene,the body weight of the model group became lower(P<0.05).The spleen and thymus were damaged,and the indexes of the spleen and thymus were decreased(P<0.05).Counts of peripheral white blood cells and lymphocyteswere decreased(P<0.05).The activities of GSH and SOD in plasma were decreased(P<0.05),but the content of MDA was increased(P<0.05).The amount of mitochondrial ROS in PBMC was increased,while the ATP content was decreased(P<0.05).The weight of mice increased after treatment with cinnamaldehyde.The spleen and thymus tissues recovered well,and the indexes of the spleen and thymus were increased(P<0.05).Counts of peripheral white blood cells and lymphocytesin the high dose cinnamaldehyde group were increased(P<0.05).The activities of GSH and SOD in plasma were increased,while the content of MDA was decreased(P<0.05).The amount of mitochondrial ROS in PBMC was decreased,but the ATP content was increased(P<0.05).Treatment with cinnamaldehyde could alleviate the damage to the mitochondrial function of PBMC induced by benzene in mice,and 50 mg/kg was the best dose(P<0.05).The therapeutic effect of cinnamaldehyde had a dose-response relationship.Conclusion Cinnamaldehyde can inhibit benzene-induced immune injury and oxidative stress injury in mice by delivering an antioxidant effect and improving mitochondrial enhancement of PBMC.
2.Syndrome of inappropriate secretion of thyrotropin: Differential diagnosis
Shasha WANG ; Zhizhen LI ; Yanyan ZHAO ; Huijuan ZHANG ; Xialian LI ; Guijun QIN ; Lili ZHENG ; Yanxia LIU ; Mengyang ZHANG ; Feng GUO
Chinese Journal of Endocrinology and Metabolism 2024;40(3):212-218
Objective:Through comprehensive analysis of symptoms and signs, biochemistry, imaging, and dynamic tests, to explore the diagnosis and differential diagnosis of thyrotropin-secreting pituitary adenoma(TSH adenoma) and syndrome of resistance to thyroid hormone(RTH).Methods:A retrospective analysis was conducted on clinical data from 14 patients who visited the First Affiliated Hospital of Zhengzhou University from July 2016 to September 2022, exhibiting elevated levels of free thyroxine(FT4) and free triiodothyronine(FT3) in the presence of increased TSH.Results:There were 7 cases of TSH adenoma and 7 cases of RTH, with the average age of diagnosis at 40.0 years and 26.6 years, respectively. Thirteen patients showed thyrotoxicosis or occasional palpitation, some with pituitary occupancy manifestations or abnormal growth and development; One patient presented with neck thickening. Sex hormone binding globulin was elevated in 3 cases of TSH adenoma. Pituitary magnetic resonance imaging showed that all 7 cases of TSH adenoma were macroadenomas and 1 case of RTH was microadenoma. The octreotide suppression test in 13 patients was inhibited, but there was a significant difference in the inhibition rate of 24 h/2 h TSH inhibition rate of TSH adenoma and RTH, ranging from 46.6% to 83.9% and 4.6% to 28.8% respectively. Six cases of RTH had thyroid hormone receptor β mutation.Conclusion:Syndrome of inappropriate secretion of thyrotropin is a rare condition, mainly including TSH adenoma and RTH. The diagnosis and differentiation of the two conditions require comprehensive assessment incorporating family history, symptoms and signs, laboratory tests, dynamic test, and genetic test. Among these, the 24 h/2 h TSH inhibition rate of octreotide suppression test can effectively distinguish TSH adenoma from RTH.
3.A comparative study on the clinical manifestations of children infected with erythromycin-resistant Bordetella pertussis of ptxP1 and ptxP3 genotypes
Mengyang GUO ; Bingsong WANG ; Lin YUAN ; Zhen LI ; Yahong HU ; Qianqian DU ; Wei SHI ; Yajuan WANG ; Kaihu YAO
Chinese Journal of Applied Clinical Pediatrics 2024;39(2):89-93
Objective:To determine the erythromycin resistance of Bordetella pertussis isolates and their ptxP1 and ptxP3 phenotypic composition and compare clinical manifestations of children with pertussis caused by the two types of strains. Methods:This was a cross-sectional study, the pertussis cases diagnosed using bacterial culture from January 2019 to December 2022 in Beijing Children′s Hospital and the First People′s Hospital of Wuhu were collected.Any suspected Bordetella pertussis colonies were identified by the slide agglutination test.The susceptibility of isolates to erythromycin was detected by the E-test and K-B test.The ptxP gene was amplified by polymerase chain reaction and sequenced to determine its genotype. t-test, Mann-Whitney U-test, Chi-square test and Fisher′s exact test were use to statistical analysis. Results:A total of 192 strains of Bordetella pertussis were identified, including 188 (97.9%) erythromycin-resistant strains.Among the 188 strains, 30.3%(57/188) belonged to the ptxP1 genotype and 69.7%(131/188) belonged to the ptxP3 genotype.In children aged below 1 year old, the incidence of paroxysmal cough caused by infection with the ptxP3 strain was higher than that with the ptxP1 strain (57.1% vs.29.4%, P<0.05), and children infected with the ptxP3 strain were more likely to develop apnea or asphyxia (23.8% vs.17.6%), post-tussive vomiting (44.4% vs.32.4%), whooping cough (72.0% vs.50.0%) and pneumonia or bronchitis (85.7% vs.73.5%) compared to those infected with the ptxP1 strain, but the differences were not statistically significant(all P>0.05). In children aged 1 year old and above, the white blood cell count of children infected with the ptxP1 strain was higher than that of infections with the ptxP3 strain [13.5(9.9, 24.5)×10 9/L, 10.3 (7.0, 16.4)×10 9/L, P<0.05], and children infected with the ptxP1 strain were more likely to contract other pathogen infections than those infected with the ptxP3 strain (17.4% vs.4.4%, P>0.05). Conclusions:ptxP3 erythromycin-resistant Bordetella pertussis has become the main pathogen of pertussis.Infants with pertussis caused by the ptxP3 erythromycin-resistant strain show more significant manifestations and a higher possibility of severe symptoms than those infected with the ptxP1 erythromycin-resistant strain.
4.Clinical Landscape of Therapeutic Cancer Vaccines: Challenges and Opportunities
Shupeng LIU ; Mengyang YU ; Xiaofei WU ; Hongyun WANG
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1356-1363
To explore the status and characteristics of clinical trials of therapeutic cancer vaccines, and provide the overall trend of clinical translational research of therapeutic cancer vaccines. The ClinicalTrial registration platform was employed to retrieve relevant clinical trial information of therapeutic cancer vaccines from 2002 to 2023. The current clinical landscape of therapeutic cancer vaccines was analyzed from the perspectives of the number of registrations, types of vaccines, trial design, and geographical distribution. A total of 1563 clinical trials for therapeutic cancer vaccines were obtained from 2002 to 2023, with an average annual registration of approximately 70 trials. Among these, phase Ⅰ trials accounted for 976 (62.4%, 976/1563), phase Ⅱ trials for 474 (30.3%, 474/1563), phase Ⅲ trials for 68 (4.4%, 68/1563), and other types for 45 (2.9%, 45/1563). Clinical trials from phase Ⅰ to phase Ⅲ were conducted in multiple regions worldwide, with multicenter clinical trials totaling 482 (31.8%) and single-center clinical trials totaling 1036 (68.2%). The main types of vaccines were cell vector vaccines (38.7%, 588/1518) and protein/peptide vaccines (34.1%, 518/1518), with the primary research designs being single-arm studies (55.3%, 840/1518) and randomized controlled trials (27.8%, 422/1518). The top five indications for the vaccines were melanoma (16.5%, 251/1518), glioblastoma (8.9%, 135/1518), breast cancer (8.6%, 130/1518), prostate cancer (8.5%, 129/1518), and lung cancer (8.1%, 123/1518). The overall development of clinical trials for therapeutic cancer vaccines has been stable and primarily focused on exploratory trials. The main types of vaccines were cell vector vaccines, and the main research designs were single-arm studies and randomized controlled trials. The vaccines were commonly indicated for melanoma, glioblastoma, and breast cancer. Currently, there are significant challenges in the clinical translation in this field, which may be due to the complexity of the immune microenvironment, patient heterogeneity, and the challenges in vaccine design and preparation. With the application of high-throughput technologies such as proteomics, genomic sequencing, and bioinformatics, it is expected that barriers in the research of therapeutic cancer vaccines would be overcome, thus leading to a better clinical translation landscape.
5.Clinical Landscape of Therapeutic Cancer Vaccines: Challenges and Opportunities
Shupeng LIU ; Mengyang YU ; Xiaofei WU ; Hongyun WANG
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1356-1363
To explore the status and characteristics of clinical trials of therapeutic cancer vaccines, and provide the overall trend of clinical translational research of therapeutic cancer vaccines. The ClinicalTrial registration platform was employed to retrieve relevant clinical trial information of therapeutic cancer vaccines from 2002 to 2023. The current clinical landscape of therapeutic cancer vaccines was analyzed from the perspectives of the number of registrations, types of vaccines, trial design, and geographical distribution. A total of 1563 clinical trials for therapeutic cancer vaccines were obtained from 2002 to 2023, with an average annual registration of approximately 70 trials. Among these, phase Ⅰ trials accounted for 976 (62.4%, 976/1563), phase Ⅱ trials for 474 (30.3%, 474/1563), phase Ⅲ trials for 68 (4.4%, 68/1563), and other types for 45 (2.9%, 45/1563). Clinical trials from phase Ⅰ to phase Ⅲ were conducted in multiple regions worldwide, with multicenter clinical trials totaling 482 (31.8%) and single-center clinical trials totaling 1036 (68.2%). The main types of vaccines were cell vector vaccines (38.7%, 588/1518) and protein/peptide vaccines (34.1%, 518/1518), with the primary research designs being single-arm studies (55.3%, 840/1518) and randomized controlled trials (27.8%, 422/1518). The top five indications for the vaccines were melanoma (16.5%, 251/1518), glioblastoma (8.9%, 135/1518), breast cancer (8.6%, 130/1518), prostate cancer (8.5%, 129/1518), and lung cancer (8.1%, 123/1518). The overall development of clinical trials for therapeutic cancer vaccines has been stable and primarily focused on exploratory trials. The main types of vaccines were cell vector vaccines, and the main research designs were single-arm studies and randomized controlled trials. The vaccines were commonly indicated for melanoma, glioblastoma, and breast cancer. Currently, there are significant challenges in the clinical translation in this field, which may be due to the complexity of the immune microenvironment, patient heterogeneity, and the challenges in vaccine design and preparation. With the application of high-throughput technologies such as proteomics, genomic sequencing, and bioinformatics, it is expected that barriers in the research of therapeutic cancer vaccines would be overcome, thus leading to a better clinical translation landscape.
6.Effects of adjuvant arthritis on renal function and expression of organic anion transporter 3 in rats
Mengyang LI ; Qianlei WANG ; Wei WEI ; Chun WANG
Acta Universitatis Medicinalis Anhui 2024;59(9):1495-1500
Objective To investigate the effects of adjuvant arthritis(AA)on renal function and the expression of organic anion transporter 3(OAT3)in rats.Methods The AA model was established via intradermal injection of Freund's complete adjuvant into the right hind toe of the rats.Blood and urine were collected at fixed time points to observe the dynamic changes of renal injury indicators.The kidney injury was observed by HE staining.Immuno-histochemistry and Western blot were used to detect the expression levels of OAT3 protein and inflammatory factors interleukin-6(IL-6),interleukin-1 β(IL-1 β)and tumor necrosis factor-α(TNF-α)in renal cortex.Results Compared with the normal group,the arthritis index score,the secondary paw swelling,the number of joint swell-ing,and the whole body score of AA rats significantly increased(P<0.05).The X-ray results showed that the AA model rats had soft tissue edema and bone deformity.Biochemical indicators showed that the renal injury indicators of AA rats were significantly abnormal.The results of immunohistochemistry and Western blot showed that the ex-pression level of OAT3 in renal cortex of AA rats significantly decreased,while the expression levels of inflammato-ry factors IL-6,TNF-α and IL-1 β significantly increased(P<0.05).Conclusion The renal injury of AA rats may be related to the decreased expression level of OAT3 and the increased expression level of inflammatory factors in kidney.
7.Effects of Different Pellet Feed Hardness on Growth and Reproduction,Feed Utilization Rate,and Environmental Dust in Laboratory Mice
Dong WU ; Rui SHI ; Peishan LUO ; Ling'en LI ; Xijing SHENG ; Mengyang WANG ; Lu NI ; Sujuan WANG ; Huixin YANG ; Jing ZHAO
Laboratory Animal and Comparative Medicine 2024;44(3):313-320
Objective To study the effects of different pellet feed hardness on the growth and reproduction,feed utilization rate,and environmental dust in laboratory mice.Methods One hundred of fifty 50 3-week-old SPF-grade C57BL/6JGpt and 150 ICR laboratory mice were randomly divided into three groups,with an equal number of males and females.They were fed diets with different hardness of 18.62 kg,23.15 kg,and 27.89 kg.Body weight,feed utilization rate,and dust levels in cages were recorded and calculated for mice aged 3-10 weeks.Forty-five 6-week-old male mice and ninety 4-week-old female mice from each strain were randomly divided into three groups and fed pellet feeds with three different hardness levels.After 2 weeks of adaptation to the same hardness feed,the mice were paired at a 1:2 male-to-female ratio and monitored for reproductive data for 3 months.Results At the age of 4 weeks,the body weight of male C57BL/6JGpt mice in 23.15 kg group was significantly higher than that in the 18.62 kg and 27.89 kg groups(P<0.01),and the body weight of females in the 18.62 kg group was significantly higher than that in the 27.89 kg group(P<0.05).There was no significant difference in body weight among ICR mice aged 3-10 weeks across different feed hardness groups(P>0.05).For both strains,feed utilization rate for males was higher than that for females across different feed hardness groups at all weeks of age(P<0.01).Compared to the 27.89 kg group,both the 18.62 kg and 23.15 kg groups showed a significant increase in the 50-mesh dust levels in cages for both strains aged 4-8 weeks(except for 7-week-old C57BL/6JGpt mice)(P<0.05).For both C57BL/6JGpt and ICR mice,there was no significant difference in basic reproductive performance such as interval between the first litter and the monthly production index among the three feed hardness groups during the experimental period(P>0.05).However,the monthly production index of C57BL/6JGpt mice first increased and then decreased with the increase of feed hardness,while that of ICR mice increased with increasing feed hardness,though these differences were not statistically significant(P>0.05).Conclusion Different strains and genders had different tolerance to feed hardness.C57BL/6JGpt mice are more adapted to lower hardness feeds,while ICR mice are better suited to slightly higher hardness feeds.
8.Influence and its mechanism of allogeneic dermal papilla cells on the wound healing of full-thickness skin defects in mice
Yage SHANG ; Lixia ZHANG ; Chao HAN ; Mengyang LI ; Liang LUO ; Xujie WANG ; Dahai HU
Chinese Journal of Burns 2024;40(8):772-780
Objective:To explore the influence and its mechanism of allogeneic dermal papilla cells (DPCs) on the wound healing of full-thickness skin defects in mice.Methods:This study was an experimental study. DPCs were isolated from the whisker follicles of five 6-week-old male C57BL/6J mice by combining microdissection with collagenase digestion and were successfully identified. Eighteen 8-week-old male C57BL/6J mice were divided into phosphate buffer solution (PBS) group and DPC group according to the random number table, with 9 mice in each group, and the full-thickness skin defect wound model was created on the back of all mice. On day 2, 4, and 6 after injury, the mice in DPC group were administered 100 μL of cell suspension containing 1×10 6 DPCs of the 4 th passage by subcutaneous injection around the wound, and the mice in PBS group was administered an equal volume of PBS. On day 3, 7, 10, and 14 after injury, the wound healing and hair growth of mice in two groups were observed, and the residual wound area was measured, and the hair coverage area on the wound of mice in two groups was measured on day 14 after injury. On day 14 after injury, the wound tissue samples of mice in two groups were collected. Hematoxylin-eosin staining was performed to observe the condition of newborn hair follicles and the number was counted, Masson staining was performed to observe the collagen deposition in the dermis and the collagen deposition area was measured, the immunofluorescence method was used to detect the protein expressions of Wnt/β-catenin signaling pathway related molecules β-catenin and lymphoid enhancer binding factor 1 (Lef1), and Western blotting and real-time fluorescence quantitative reverse transcription polymerase chain reaction were used to detect the protein and mRNA expressions of β-catenin and Lef1, respectively. The number of samples in each experiment was 3. Results:Compared with those in PBS group, the mice in DPC group had accelerated wound re-epithelialization at each time point after injury, and more hair growth on day 10 and 14 after injury. On day 7, 10, and 14 after injury, the residual wound areas of mice in DPC group were (13.92±2.90), (3.69±1.78), and (1.09±0.14) mm 2, respectively, which were significantly smaller than (26.19±2.06), (10.84±3.59), and (6.75±2.11) mm 2 in PBS group, respectively (with t values of 5.85, 3.09, and 4.63, respectively, P values all <0.05). On day 14 after injury, the hair coverage area on the wound of mice in DPC group was (62±7) mm 2, which was significantly larger than (35±6) mm 2 in PBS group ( t=2.89, P<0.05). On day 14 after injury, compared with those in PBS group, the number of newborn hair follicles in the wound tissue of mice in DPC group was significantly increased ( t=5.43, P<0.05), and the dermal collagen deposition area was significantly reduced ( t=3.56, P<0.05). On day 14 after injury, both the immunofluorescence method and the Western blotting detection showed that the protein expressions of β-catenin (with t values of 5.49 and 4.25, respectively, P values all <0.05) and Lef1 (with t values of 7.50 and 11.54, respectively, P values all <0.05) in the wound tissue of mice in DPC group were significantly higher than those in PBS group; the mRNA expressions of β-catenin and Lef1 in the wound tissue of mice in DPC group were significantly higher than those in PBS group (with t values of 7.68 and 9.67, respectively, P<0.05). Conclusions:DPCs can accelerate the re-epithelialization of full-thickness skin defect wounds in mice by activating Wnt/β-catenin signaling pathway and promote hair follicle regeneration during the process of wound healing.
9.Regulation of cyclicGMP-AMP synthase function by protein post-translational modifications
Mengyang SHEN ; Chen LU ; Yi WANG ; Jinyong PEI ; Jie WANG ; Bo YANG
Journal of Xinxiang Medical College 2024;41(8):701-705
The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes signaling pathway plays a central role in cells'ability to sense the presence of abnormal double-stranded DNA within the cytoplasm.Modulation of the function of the cytoplasmic DNA recognition receptor cGAS allows regulation of this signaling pathway.In recent years,research has identified protein post-translational modifications(PTMs),including phosphorylation,acetylation,ubiquitination,methylation,and SUMOylation,as having significant roles in regulating innate immune signaling pathways.This paper reviews how PTMs influence the function of cGAS and its downstream signaling pathways through various mechanisms.
10.Construction of Longitudinal Comprehensive Evaluation Model of Disease Treatment Quality and Its Application in CIS
Lei YU ; Mengyang LIU ; Chao WANG
Chinese Journal of Health Statistics 2024;41(5):662-666,670
Objective Construct a longitudinal comprehensive evaluation model of disease treatment quality to evaluate the quality of treatment for cerebral ischemic stroke(CIS).Methods The latent variable measurement model was combined with polynomial and multilevel regression to establish a longitudinal comprehensive evaluation model of disease treatment quality,the MCMC was used for parameter estimation.Simulation studies were conducted to determine the applicable conditions of the model,the accuracy of model parameter estimation was evaluated by root mean square error and rank correlation coefficient,the results were compared with the latent growth curve model(LGCM).Results A comprehensive model that can be used to evaluate the longitudinal change,trend change and the impact of covariates in the quality of disease care was constructed.The number of evaluation objects has a little effect on the model effect.When the number of observation time was 6 and the number of evaluation indicators was 20,the model could obtain the treatment quality and change trend of the evaluation object at different time points.The mean rank correlation coefficient between the estimated value of treatment quality and the true value was 0.8128,which was higher than that of LGCM(0.7610).The mean RMSE between the estimated value of the covariate regression coefficient and the true value was 0.3756,which was lower than that of LGCM(0.448).The more observation time and evaluation indexes,the more accurate the longitudinal comprehensive evaluation model was,and it was always higher than LGCM.From 2011 to 2016,the average CIS quality of care comprehensive score of hospitals increased by 0.9256,secondary and tertiary hospitals increased by 0.9432 and 1.321,teaching and non-teaching hospitals increased by 1.4904 and 1.1155.Conclusion The longitudinal comprehensive evaluation model can comprehensively and reasonably evaluate the quality of disease treatment and its longitudinal changes,and analyze the impact of differences in evaluation objects on the change trend.The quality of CIS treatment in China is generally good,and the changing trend is affected by the level of hospitals and teaching status.The results of this study can provide reference for the subsequent development of targeted treatment quality intervention measures and continuous improvement of treatment quality.


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