1.Improvement of myocardial injury by traditional Chinese medicine:mitochondrial calcium homeostasis mediates macrophage autophagy and pyroptosis pathway
Lingyun LIU ; Guixin HE ; Weibin QIN ; Hui SONG ; Liwen ZHANG ; Weizhi TANG ; Feifei YANG ; Ziyi ZHU ; Yangbin OU
Chinese Journal of Tissue Engineering Research 2025;29(6):1276-1284
BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.
2.Impact of Antibody Immune Response and Immune Cells on Osteoporosis and Fractures
Kangkang OU ; Jiarui CHEN ; Jichong ZHU ; Weiming TAN ; Cheng WEI ; Guiyu LI ; Yingying QIN ; Chong LIU
Clinics in Orthopedic Surgery 2025;17(3):530-545
Background:
The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis.
Methods:
We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved.
Results:
Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects.
Conclusions
This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.
3.Impact of Antibody Immune Response and Immune Cells on Osteoporosis and Fractures
Kangkang OU ; Jiarui CHEN ; Jichong ZHU ; Weiming TAN ; Cheng WEI ; Guiyu LI ; Yingying QIN ; Chong LIU
Clinics in Orthopedic Surgery 2025;17(3):530-545
Background:
The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis.
Methods:
We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved.
Results:
Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects.
Conclusions
This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.
4.Impact of Antibody Immune Response and Immune Cells on Osteoporosis and Fractures
Kangkang OU ; Jiarui CHEN ; Jichong ZHU ; Weiming TAN ; Cheng WEI ; Guiyu LI ; Yingying QIN ; Chong LIU
Clinics in Orthopedic Surgery 2025;17(3):530-545
Background:
The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis.
Methods:
We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved.
Results:
Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects.
Conclusions
This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.
5.Impact of Antibody Immune Response and Immune Cells on Osteoporosis and Fractures
Kangkang OU ; Jiarui CHEN ; Jichong ZHU ; Weiming TAN ; Cheng WEI ; Guiyu LI ; Yingying QIN ; Chong LIU
Clinics in Orthopedic Surgery 2025;17(3):530-545
Background:
The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis.
Methods:
We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved.
Results:
Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects.
Conclusions
This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.
6.Follow-up Study on Resolution of Pulmonary Consolidation in 238 Children with Mycoplasma Pneumoniae Pneumonia
Yuexu OU ; Xiaomin GAN ; Bin QIN ; Zhengxiu LUO ; Jie CAO
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(5):899-906
ObjectiveTo analyze the clinical characteristics and imaging features of effectively treated pediatric Mycoplasma pneumoniae pneumonia (MPP) with pulmonary consolidation, follow up the volume changes of pulmonary consolidation on lung CT scans of the affected children, and investigate the resolution patterns of pulmonary consolidation, and predict the time required for complete resolution. MethodsWe enrolled children with MPP and pulmonary consolidation hospitalized in the Department of General Pediatrics at Children's Hospital of Chongqing Medical University between January 2018 and May 2024. Data collected included demographics, clinical symptoms, laboratory indicators, treatment status, imaging data during hospitalization, as well as follow-up lung CT data and reexamination intervals after discharge. Consolidation volumes were measured before and after the treatment to calculate the resolution rate and resolution velocity. Descriptive statistical analysis was performed on clinical characteristics, imaging features and consolidation resolution. ResultsAmong 238 children with MPP and lung consolidation, females slightly outnumbered males (the male to female ratio is 109 vs.129), with a mean age of approximately 5 years. At admission, the median cough and fever durations were 7 (5-9) days and 6 ( 4-7) days, respectively. No significant increase was found in white blood cells count or lactate dehydrogenase(LDH), and hypersensitive high-sensitivity C-reactive protein (CRP) slightly increased. Azithromycin was the first line of treatment in most cases, though second-line drugs increased in the recent two years due to the rising resistance. Bronchoalveolar lavage was performed in 66.8% (159/238) of children, and 33.2% (79/238) did not receive lavage. Consolidation was predominantly unilateral (206 unilateral vs. 32 bilateral) and right-sided (117 right-sided vs. 89 left-sided). The ratio of consolidation volume to total lung volume was 4.48 (2.61-7.35) %, the consolidation resolution rate at follow-up was 96.08 ( 88.02-98.95) %, the reexamination interval was 17 ( 15-21) days, the resolution velocity was 2.15 (1.23-4.01) cm3/d, and the time to complete resolution was 18.96 (16.14-23.33) days . ConclusionsPulmonary consolidation in pediatric MPP achieves substantial resolution on CT within 2-3 weeks after effective clinical treatment. Initial consolidation volume and resolution velocity can predict the time required for complete resolution, thereby clinically guiding optimal CT follow-up scheduling.
7.Ameliorative effects of Ziyin Mingmu Pills on mouse retinitis pigmentosa by activating the sonic hedgehog factor signaling pathway
Mei-Yan ZENG ; Meng XIONG ; Hou-Pan SONG ; Chen OU ; Chao-Jun FU ; Qing-Hua PENG ; Yu-Hui QIN
Chinese Traditional Patent Medicine 2024;46(8):2551-2561
AIM To explore the ameliorative effects of Ziyin Mingmu Pills on mouse retinitis pigmentosa(RP)and the possible mechanism.METHODS The RP transgenic mice(rd10)were randomly divided into the model group,the Leding group(0.15 g/kg)and the low and high dose Ziyin Mingmu Pills groups(4.50,9.00 g/kg),in contrast to the C57BL/6 mice of the normal group,with 12 mice in each group.The mice had their retinal pathological changes detected by HE staining;their visual function detected by electroretinogram(ERG);their fundus conditions and retinal thickness detected by optical coherence tomography(OCT);their retinal blood perfusion detected by laser speckle blood flow technique;their mRNA expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA detected by digital PCR;and their protein expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin detected by immunofluorescence staining.RESULTS Compared with the normal group,the model group displayed pathological changes in the fundus and retina and decreased amplitudes of ERG a wave and b wave(P<0.01);decreased retinal thickness(P<0.01);decreased retinal blood perfusion(P<0.01);and decreased retinal expressions of Shh,Ptc,Smo,Gli1,N-myc,Cyclin mRNA and protein(P<0.01).Compared with the model group,the groups intervened with Ziyin Mingmu Pills or Leding shared improved pathological changes in the fundus and retina tissue,and increased retinal thickness(P<0.01);increased retinal blood flow(P<0.01);increased amplitudes of ERG a wave and b wave(P<0.01);and increased retinal Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA and protein expressions(P<0.01).CONCLUSION Ziyin Mingmu Pills can improve the fundus pathological changes and visual function to delay RP in mice because of their efficacy in ameliorating retinal thickness and blood flow possibly by activating Shh signaling pathway.
8.Promoting the implementation of delayed cord clamping in very preterm infants by quality improvement method
Sijie SONG ; Jiangfeng OU ; Nuo QIN ; Yefang ZHU ; Yan WU ; Hua GONG ; Wen CHEN ; Junying YE ; Xiaoyun ZHONG
Chinese Journal of Perinatal Medicine 2024;27(6):490-498
Objective:To investigate the effect of quality improvement (QI) project on delayed cord clamping (DCC) implementation in very preterm infants.Methods:This study retrospectively collected the clinical data and assessed the QI indices of very preterm infants born in the Women and Children's Hospital of Chongqing Medical University and transferred to the Neonatology Department from January 2017 to January 2021. The indices for QI assessment included three types: (1) process indices: the implementation rate and timing of DCC; (2) outcome indices: hemoglobin level and hematocrit, etc; (3) balancing indices: the proportion of neonates requiring endotracheal intubation in the delivery room and chest compressions, Apgar score body temperature, and blood pH value on admission, etc. There were four phases for the implementation of QI, the pre-QI period (January to December of 2017), the QI period (January to December of 2018), the post-QI period (January to December of 2019), and the sustained-QI period (January 2020 to January 2021). The QI project was performed since August 2018. Control charts or statistical tests were used for statistical analysis.Results:(1) Process indices: After the implementation of the QI project, the practice of DCC increased from 0 to 82.2%, and the timing of umbilical cord clamping was from 0 s to a delay of 47.1 s. (2) Outcome indices: The levels of hemoglobin in the QI period, the post-QI period, and the sustained-QI period were significantly higher than those in the pre-QI period [(202.22±28.84), (210.10±33.52), (210.52±32.27) g/L vs. (187.94±35.29) g/L; F=8.61, P<0.001]. The hematocrit values in the post-QI period and the sustained-QI period were significantly higher than those in the pre-QI period [(58.99±8.71) %, (60.18±8.06)% vs. (55.41±9.17)%; χ2=5.13, P=0.002]. The other indices showed no statistical differences in different phases. (3) Balancing indices: The proportions of neonates receiving endotracheal intubation in the delivery room in the post-QI period and the sustained-QI period were significantly lower than those in the pre-QI period [16.0% (19/119), 13.2% (25/191) vs. 42.3% (30/71); χ2=29.08, P<0.001]. The body temperature on admission increased gradually through the four periods [pre-QI period: 35.3 ℃ (34.5-36.1 ℃); QI period: 36.0 ℃ (34.0-37.7 ℃); post-QI period: 36.0 ℃ (35.6-37.4 ℃); sustained-QI period: 37.0 ℃ (35.9-38.1 ℃); H=277.88, P<0.001]. The blood pH value on admission in the sustained-QI period [7.32 (6.85-7.50)] was significantly higher than those in the other three periods [7.26 (7.07-7.46), 7.26 (7.04-7.43), and 7.25 (6.91-7.49); H=34.46, P<0.001]. Conclusion:The interventions in this QI project significantly increase the practice of DCC and enable a longer DCC in very preterm infants.
9.Evidence-based evaluation of the global cancer-associated thromboembolism risk assessment tools
Xiaoli QIN ; Xiurong GAO ; Qin HE ; Shunlong OU ; Jing LUO ; Hua WEI ; Qian JIANG
China Pharmacy 2024;35(3):333-338
OBJECTIVE To evaluate the global cancer-associated thromboembolism risk assessment tools based on evidence- based methods, and to provide methodological reference and evidence-based basis for constructing a specific tool in China. METHODS A comprehensive search was conducted on 6 databases, including CNKI, Wanfang data, VIP, CBM, PubMed, and Embase, as well as on the websites of NCCN, ASCO, ESMO and so on with a deadline of June 30, 2022. Furthermore, a supplementary search was conducted in January 2023. The essential characteristics and methodological quality of included risk assessment tools were described and analyzed qualitatively, focusing on comparing each assessment stratification ability. RESULTS Totally 14 risk assessment tools were included in the study, with a sample size of 208-18 956 cases and an average age distribution of 53.1-74.0 years. The applicable population included outpatient cancer student@sina.com patients, lymphoma patients, and multiple myeloma patients,etc. The common predictive factors were body mass index, venous thromboembolism history, and tumor site. All tools had undergone methodological validation, with 9 presented in a weighted scoring format. Only seven tools were used simultaneously for specificity, sensitivity, negative predictive value (NPV), positive predictive value (PPV) and area under the curve (AUC) or C statistical analysis. CONCLUSIONS The risk of bias in constructing existing tools is high, and the heterogeneity of tool validation results is significant. The overall methodological quality must be improved, and its risk stratification ability must also be investigated. There are still certain limitations in clinical practice in China.
10.Identification of inflammatory response genes in ANCA-associated vasculitis by bioinformatics analysis and experimental validation
Dongmei ZHANG ; Yannan ZHANG ; Jianhua QIN ; Santao OU ; Weihua WU
Acta Universitatis Medicinalis Anhui 2024;59(4):581-589
Objective To explore the candidate genes and potential molecular mechanisms of anti-neutrophil cyto-plasmic antibodies(ANCA)-associated vasculitis by bioinformatics and experimental validation,and to provide a scientific theoretical basis for the treatment of potential inflammatory targets for ANCA-associated vasculitis.Meth-ods The GSE108109 chip data was retrieved from the Gene Expression Omnibus(GEO)database,and the differ-ential genes were processed,analyzed and screened using the R language related program package.Kyoto encyclo-pedia of genes and genomes(KEGG)and gene ontology(GO)enrichment analysis was carried out using DAVID online network cable,and the interaction network of the protein encoded by the selected genes of inflammatory syn-drome was constructed through STRING website.Further endogenous competitive RNA(ceRNA)regulatory net-work was predicted and constructed through miRWalk and DIANA-LncBase databases,and key genes were screened from the network to draw ROC curve.The renal biopsy samples of patients with ANCA-associated vasculi-tis confirmed by our hospital were collected as the experimental group,and the renal biopsy samples of IgA ne-phropathy and micro-adaptive nephropathy were collected as the control group.Immunohistochemical staining was performed on the collected renal biopsy samples,and the average optical density was calculated by semi-quantita-tive analysis of immunohistochemical staining to further verify the expression of the key genes screened by the bioin-formatics analysis.Pearson linear correlation analysis was performed between the average optical density results and the clinical inflammatory data of patients.Results 846 differential genes were screened,of which 444 genes were significantly up-regulated and 402 genes were significantly down-regulated.Through KEGG and GO analysis,im-portant differentially expressed genes related to inflammation regulation were obtained.Among them,CSF1R and TNFRSF1B,two differentially expressed genes never reported in ANCA-associated vasculitis,attracted our atten-tion.At the same time,we constructed multiple ceRNA regulatory axes including KCNQ1OT1-hsa-miR-125a-5p-TNFRSF1B.There were 15 samples of ANCA-associated vasculitis,6 samples of IgA nephropathy,and 3 samples of micropathological kidney.Immunohistochemical results of renal biopsy specimens showed that the expression of CSF1R and TNFRSF1B in ANCA-associated vasculitis kidney tissue was higher than that in the control group.Pearson correlation analysis of clinical data of patients in ANCA group showed that the expression of CSF1R was positively correlated with the content of neutrophil count(r=0.587),and the expression of TNFRSF1B was posi-tively correlated with the content of serum C-reactive protein(r=0.646).Conclusion Key genes related to in-flammatory regulation such as CSF1R and TNFRSF1B were investigated by bioinformatics methods,and a rigorous ceRNA regulatory network was constructed.The expression of CSF1R and TNFRSF1B in ANCA vasculitis was high-er than that in the control group through immunohistochemistry.The results provides a scientific theoretical basis for the molecular mechanism of inflammation,and laid a good foundation for new therapeutic targets of ANCA-related vasculitis for inflammation.


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