1.Fucoidan sulfate regulates Hmox1-mediated ferroptosis to ameliorate myocardial injury in diabetic cardiomyopathy.
Yu-Feng CAI ; Wei HU ; Yi-Gang WAN ; Yue TU ; Si-Yi LIU ; Wen-Jie LIU ; Liu-Yun-Xin PAN ; Ke-Jia WU
China Journal of Chinese Materia Medica 2025;50(9):2461-2471
This study explores the role and underlying molecular mechanisms of fucoidan sulfate(FPS) in regulating heme oxygenase-1(Hmox1)-mediated ferroptosis to ameliorate myocardial injury in diabetic cardiomyopathy(DCM) through in vivo and in vitro experiments and network pharmacology analysis. In vivo, a DCM rat model was established using a combination of "high-fat diet feeding + two low-dose streptozotocin(STZ) intraperitoneal injections". The rats were randomly divided into four groups: normal, model, FPS, and dapagliflozin(Dapa) groups. In vitro, a cellular model was created by inducing rat cardiomyocytes(H9c2 cells) with high glucose(HG), using zinc protoporphyrin(ZnPP), an Hmox1 inhibitor, as the positive control. An automatic biochemical analyzer was used to measure blood glucose(BG), serum aspartate aminotransferase(AST), serum lactate dehydrogenase(LDH), and serum creatine kinase-MB(CK-MB) levels. Echocardiography was used to assess rat cardiac function, including ejection fraction(EF) and fractional shortening(FS). Pathological staining was performed to observe myocardial morphology and fibrotic characteristics. DCFH-DA fluorescence probe was used to detect reactive oxygen species(ROS) levels in myocardial tissue. Specific assay kits were used to measure serum brain natriuretic peptide(BNP), myocardial Fe~(2+), and malondialdehyde(MDA) levels. Western blot(WB) was used to detect the expression levels of myosin heavy chain 7B(MYH7B), natriuretic peptide A(NPPA), collagens type Ⅰ(Col-Ⅰ), α-smooth muscle actin(α-SMA), ferritin heavy chain 1(FTH1), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), 4-hydroxy-2-nonenal(4-HNE), and Hmox1. Immunohistochemistry(IHC) was used to examine Hmox1 protein expression patterns. FerroOrange and Highly Sensitive DCFH-DA fluorescence probes were used to detect intracellular Fe~(2+) and ROS levels. Transmission electron microscopy was used to observe changes in mitochondrial morphology. In network pharmacology, FPS targets were identified through the PubChem database and PharmMapper platform. DCM-related targets were integrated from OMIM, GeneCards, and DisGeNET databases, while ferroptosis-related targets were obtained from the FerrDb database. A protein-protein interaction(PPI) network was constructed for the intersection of these targets using STRING 11.0, and core targets were screened with Cytoscape 3.9.0. Molecular docking analysis was conducted using AutoDock and PyMOL 2.5. In vivo results showed that FPS significantly reduced AST, LDH, CK-MB, and BNP levels in DCM model rats, improved cardiac function, decreased the expression of myocardial injury proteins(MYH7B, NPPA, Col-Ⅰ, and α-SMA), alleviated myocardial hypertrophy and fibrosis, and reduced Fe~(2+), ROS, and MDA levels in myocardial tissue. Furthermore, FPS regulated the expression of ferroptosis-related markers(Hmox1, FTH1, SLC7A11, GPX4, and 4-HNE) to varying degrees. Network pharmacology results revealed 313 potential targets for FPS, 1 125 targets for DCM, and 14 common targets among FPS, DCM, and FerrDb. Hmox1 was identified as a key target, with FPS showing high docking activity with Hmox1. In vitro results demonstrated that FPS restored the expression levels of ferroptosis-related proteins, reduced intracellular Fe~(2+) and ROS levels, and alleviated mitochondrial structural damage in cardiomyocytes. In conclusion, FPS improves myocardial injury in DCM, with its underlying mechanism potentially involving the regulation of Hmox1 to inhibit ferroptosis. This study provides pharmacological evidence supporting the therapeutic potential of FPS for DCM-induced myocardial injury.
Animals
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Ferroptosis/drug effects*
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Rats
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Diabetic Cardiomyopathies/physiopathology*
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Male
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Rats, Sprague-Dawley
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Polysaccharides/pharmacology*
;
Heme Oxygenase-1/genetics*
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Myocytes, Cardiac/metabolism*
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Myocardium/pathology*
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Humans
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Cell Line
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Heme Oxygenase (Decyclizing)
2.Effects of Saccharomyces cerevisiae chassis cells with different squalene content on triterpenoid synthesis.
Feng ZHANG ; Kang-Xin HOU ; Yue ZHANG ; Hong-Ping HOU ; Yue ZHANG ; Chao-Yue LIU ; Xue-Mi HAO ; Jia LIU ; Cai-Xia WANG
China Journal of Chinese Materia Medica 2025;50(8):2130-2136
Many triterpenoid compounds have been successfully heterologously synthesized in Saccharomyces cerevisiae. To increase the yield of triterpenoids, various metabolic engineering strategies have been developed. One commonly applied strategy is to enhance the supply of precursors, which has been widely used by researchers. Squalene, as a precursor to triterpenoid biosynthesis, plays a crucial role in the synthesis of these compounds. This study primarily investigates the effect of different squalene levels in chassis strains on the synthesis of triterpenoids(oleanolic acid and ursolic acid), and the underlying mechanisms are further explored using real-time quantitative PCR(qPCR) analysis. The results demonstrate that the chassis strain CB-9-5, which produces high levels of squalene, inhibits the synthesis of oleanolic acid and ursolic acid. In contrast, chassis strains with moderate to low squalene production, such as Y8-1 and CNPK, are more conducive to the synthesis of oleanolic acid and ursolic acid. The qPCR analysis reveals that the expression levels of ERG1, βAS, and CrCYP716A154 in the oleanolic acid-producing strain CB-OA are significantly lower than those in the control strains C-OA and Y-OA, suggesting that high squalene production in the chassis strains suppresses the transcription of certain genes, leading to a reduced yield of triterpenoids. Our findings indicate that when constructing S. cerevisiae strains for triterpenoid production, chassis strains with high squalene content may suppress the expression of certain genes, ultimately lowering their production, whereas chassis strains with moderate squalene levels are more favorable for triterpenoid biosynthesis.
Squalene/analysis*
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Saccharomyces cerevisiae/genetics*
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Triterpenes/metabolism*
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Metabolic Engineering
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Oleanolic Acid/biosynthesis*
;
Ursolic Acid
3.Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production.
Ya-Jie CAI ; Jian-Hang LAN ; Shuo LI ; Yue-Ning FENG ; Fang-Hong LI ; Meng-Yu GUO ; Run-Ping LIU
Journal of Integrative Medicine 2025;23(4):429-444
OBJECTIVE:
Ulcerative colitis is closely associated with intestinal stem cell (ISC) loss and impaired intestinal mucus barrier. Sinisan (SNS), a compound Chinese herbal medicine, has a long history in the treatment of intestinal dysfunction, yet whether SNS can relieve acute experimental colitis by modulating ISC proliferation and secretory cell differentiation has not been studied. Our study tested the effect of SNS against acute colitis and focused on the mechanisms involving intestinal barrier recovery.
METHODS:
Network pharmacology analysis and blood entry component analysis of SNS were used to explore the underlying mechanism by which SNS affects the acute dextran sulfate sodium (DSS)-induced murine colitis model. RNA-sequencing was used to demonstrate the mechanism. Further, reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining, and alcian blue and periodic acid-Schiff staining were performed in vivo and in the colonic organoids to investigate the cell lineage differentiation-related mechanism of SNS. Furthermore, potential active ingredients from SNS were predicted by network pharmacology analysis.
RESULTS:
SNS dramatically suppressed DSS-induced acute colonic inflammation in mice. RNA-sequencing analysis revealed downregulation of inflammation and apoptosis-related genes, and upregulation of lipid metabolism and proliferation-related genes, such as Irf7, Pparα, Clspn and Hspa5. Additionally, ISC renewal and intestinal secretory cell lineage commitment were significantly promoted by SNS both in vivo and in vitro in colonic organoids, leading to enhanced mucin expression. Furthermore, potential active ingredients from SNS that mediated inflammation, lipid metabolism, proliferation, apoptosis, stem cells and secretory cells were predicted using a network pharmacology approach.
CONCLUSION
Our study shed light on the underlying mechanism of SNS in attenuating acute colitis from the perspective of ISC renewal and secretory lineage cell differentiation, suggesting a of novel therapeutic strategy against colitis. Please cite this article as: Cai YJ, Lan JH, Li S, Feng YN, Li FH, Guo MY, et al. Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production. J Integr Med. 2025; 23(4): 429-444.
Animals
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Drugs, Chinese Herbal/therapeutic use*
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Mice
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Colon/pathology*
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Mucins/metabolism*
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Mice, Inbred C57BL
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Cell Differentiation/drug effects*
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Male
;
Colitis/metabolism*
;
Cell Lineage/drug effects*
;
Dextran Sulfate
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Stem Cells/drug effects*
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Disease Models, Animal
4.HIV Pretreatment Drug Resistance and Transmission Clusters among Newly Diagnosed Patients in the China-Myanmar Border Region, 2020-2023.
Huan LIU ; Yue Cheng YANG ; Xing DUAN ; Yi Chen JIN ; Yan Fen CAO ; Yi FENG ; Chang CAI ; He He ZHAO ; Hou Lin TANG
Biomedical and Environmental Sciences 2025;38(7):840-847
OBJECTIVE:
This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China.
METHODS:
Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site.
RESULTS:
Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL.
CONCLUSION
The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans
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HIV Infections/virology*
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China/epidemiology*
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Drug Resistance, Viral
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Male
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Adult
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Female
;
Middle Aged
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HIV-1/genetics*
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Anti-HIV Agents/therapeutic use*
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Myanmar/epidemiology*
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Young Adult
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Prevalence
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Adolescent
;
Mutation
5.Clinical laboratory testing and molecular epidemiological characterization of influenza A virus in a hospital in Henan Province from 2016-2024
Haixia WANG ; Yue WU ; Jingjing CAI ; Yingying ZHAO ; Yangfan FENG ; Qing CHEN ; Kai DU ; Shulin ZHANG ; Xuedong ZHANG
Chinese Journal of Laboratory Medicine 2025;48(9):1185-1193
Objective:To investigate the methodological differences in the detection, the inflammatory markers and the pathogenic epidemiological characteristics of influenza A virus in clinical laboratories, in order to provide more diagnostic and epidemiological data for diagnosis and prevention for children with influenza A.Methods:A retrospective cross-sectional study was conducted to collect 96 731 patients with suspected influenza A from January 2016 to October 2024 in Nanyang City Center Hospital from the Clinical Laboratory Testing Information System, including 5 731 patients with confirmed influenza A, aged 5.2 (2.8, 43.7) years old. We analyzed the distribution of influenza A patients from age and mixed infections, the relationship between patient age and positive detection rate by restricted cubic spline (RCS), analyzed differences in testing methods used Kappa consistency testing and receiver operating characteristic (ROC) curves, established a model of inflammatory markers by logistic regression, as well as developed a prediction model and also the mutation of the hemagglutinin (HA) sequence of the influenza A subtype H3N2 virus using evolutionary tree analysis.Results:RCS analysis showed an inverted 'S' shaped non-linear relationship between the positive detection rate of influenza A and the age groups of the patients. Among the mixed infections, 1.43%(1 352/94 867) of the cases were combined with Mycoplasma pneumoniae infection. The Kappa values of reverse transcription PCR (RT-PCR) and serological indirect immunofluorescence assay (IFA) for detecting influenza A in nasopharyngeal swabs and alveolar lavage fluid in clinical laboratories were 0.632 and 0.809, respectively, and those of magnetic particle chemiluminescence assay were 0.614 and 0.668, respectively, and the area under curves in ROC curve of IFA and RT-PCR were 0.869 and 0.792, respectively. The inflammatory indexes were usually elevated in severe children compared with mild children. By binary logistic regression model analysis, neutrophil-to-lymphocyte ratio, D-dimer/fibrinogen and prognosis nutrition index were the risk factors and serum amyloid A/C reactive protein ratio was the protective factor for severe children with influenza A, and the OR values of the above factors were 1.760, 7.076, 1.045, and 0.719, respectively, and P<0.01. By the Bayesian Interdiction Criterion, the optimal seasonal autoregressive moving average mixed model for influenza A epidemics was ARIMA (1, 1, 1) (2, 1, 2) 12 with the highest prediction accuracy of 98.63%. The seven strains of H3N2 all belonged to the same isoforms, with nucleotide similarity of the HA gene ranging from 99.5% to 99.9%, and the glycosylation site, receptor-binding site, and the conserved amino acid residue Glycosylation sites, receptor binding sites and conserved amino acid residues remained unchanged. HA sequence analysis showed that the prevalent strains in Nanyang had undergone mutation to different degree compared with the vaccine strains. Conclusion:Scientific and rational testing and characteristic inflammatory markers in the clinical laboratory are of great clinical value in the diagnosis of children with severe influenza A. At the same time, the epidemiological monitoring of influenza A variants should be strengthened.
6.Co-Cr-Mo guided multidirectional sliding growing rod technology for the treatment of type I neurofibromatosis induced early-onset scoliosis
Feng ZHU ; Wei MEI ; Yu YUE ; Hongjie MA ; Changtao MENG ; Dongliang CAI ; Xiangjian SONG
Chinese Journal of Orthopaedics 2025;45(7):402-411
Objective:To explore the differences in clinical efficacy between Co-Cr-Mo guided multidirectional sliding growing rod technology (CMSG) and traditional growing rod in the treatment of neurofibromatosis type 1 dysplastic early-onset scoliosis.Methods:A retrospective analysis was conducted on the data of 20 patients with neurofibromatosis type 1 dysplastic early-onset scoliosis who underwent surgical treatment in the Scoliosis Department of Zhengzhou Orthopaedic Hospital Affiliated to Henan University from January 2010 to July 2022. There were 10 patients in the traditional rod group (treated with traditional growing rod surgery) and 10 patients in the CMSG group (treated with CMSG technology). All patients were ≤10 years old and had a Cobb angle ≥45°. The number of surgeries and the occurrence of complications were recorded. The Cobb angle of the main scoliotic curve, the Cobb angle of kyphosis from T 5 to T 12, and the height from T 1 to S 1 were measured from the imaging data to evaluate the correction of deformity and spinal growth. Results:There were no significant differences in age, gender, follow - up time, preoperative Cobb angle, and preoperative Cobb angle of kyphosis from T 5-T 12 between the CMSG group and the TGR group ( P>0.05). The number of surgeries 1.3±0.67 and the total medical cost 91, 100±34, 700 yuan in the CMSG group were lower than those in the TGR group (5.3±1.77 times and 155, 800±45, 900 yuan], and the differences were statistically significant ( t=6.687, P<0.001; t=3.558, P=0.002). The Cobb angles of the main curve before surgery, after the first surgery, and at the last follow - up in the CMSG group were 69.7°±17.8°, 19.8°±9.7°, and 24.4°±9.0° respectively, while those in the TGR group were 62.0°±11.1°, 32.1°±11.4°, and 33.3°±11.6° respectively. The differences in Cobb angles after the first surgery and at the last follow-up between the two groups were statistically significant ( t=2.633, P=0.017; t=2.313, P=0.033). The Cobb angles of kyphosis from T 5 to T 12 before surgery, after the first surgery, and at the last follow - up in the CMSG group were 40.0°±24.2°, 21.0°±6.0°, and 33.6°±9.3° respectively, while those in the TGR group were 31.3°±14.5°, 26.3°±10.5°, and 32.3°±17.2° respectively. There were no significant differences in the Cobb angles of kyphosis from T 5 to T 12 after the first surgery and at the last follow-up between the two groups ( t=1.383, P=0.184; t=0.243, P=0.811). The heights from T 1 to S 1 before surgery, after the first surgery, and at the last follow-up in the CMSG group were 30.5±3.4 cm, 33.7±3.3 cm, and 37.9±4.8 cm respectively, with an annual increase of 1.18±0.39 cm. The heights from T 1 to S 1 in the TGR group were 29.1±3.0 cm, 31.4±2.9 cm, and 36.3±3.5 cm respectively, with an annual increase of 1.25±0.23 cm. There was no significant difference in the annual growth height of T 1-S 1 between the two groups ( t=1.367, P=0.189). During the follow-up period, 3 patients in the CMSG group had 3 complications: 1 case of coronal plane trunk decompensation, 1 case of rod fracture, and 1 case of distal junctional kyphosis. In the TGR group, 7 patients had 8 complications: 2 cases of wound rupture, 3 cases of screw loosening, 1 case of distal addition phenomenon, 1 case of proximal addition phenomenon, and 1 case of rod fracture. Conclusion:The Co-Cr-Mo guided multidirectional sliding growing rod technique is safe and effective in treating type 1 neurofibromatosis with malnutrition type early-onset scoliosis. It can effectively control the progression of spinal deformities,preserve the growth ability of the spine, and have a low overall incidence of complications.
7.Transcatheter aortic valve implantation for native aortic valve regurgitation:single-centre experience
Xiao-xue ZHANG ; Yi FENG ; Xian-tao MA ; Yu-jie YANG ; Akilu WAJEEHULLAHI ; Chen-xi YAN ; Zi-yue ZHANG ; Zi-jun CHEN ; Bo QIN ; Shi-liang LI ; Cai CHENG
Chinese Journal of Interventional Cardiology 2025;33(1):33-41
Objective To evaluate the efficacy and safety of transcatheter aortic valve implantation(TAVI)for the treatment of primary aortic valve regurgitation(NAVR)and to compare the difference in the choice of prosthetic valve size and the difference in complications with aortic stenosis(AS).Methods According to the definition of Valve Academic Research Consortium(VARC-3),143 patients with NAVR/AS treated with TAVI and patients with NAVR treated with surgical aortic valve replacement(SAVR)at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China,from March 2019 to September 2024 were selected,and clinical data on baseline,perioperative,and primary endpoint events were were retrospectively collected and compared.Results Forty-three patients with NAVR were treated with TAVI,with a device success rate of 86.0%and a surgical success rate of 95.3%.Subgroup comparisons:(1)NAVR-TAVI group than NAVR-SAVR group:patients in the TAVI group had a significantly shorter operative time than those in the SAVR group(P<0.001);complete left bundle branch block was more likely to occur after TAVI(P=0.042),and complete right bundle branch block was more likely to occur after SAVR(P=0.044).SAVR postoperatively The incidence of congestive heart failure was higher(P=0.013),and the mortality rate was significantly higher in the SAVR group than in the TAVI group(P=0.019).(2)NAVR-TAVI group than AS-TAVI group:the differences in access selection,THV size[28(22,34)mm vs.24(22,32)mm,P=0.044]and proportion of THV overdiameter[14%(7%,20%)vs.7%(3%,11%),P<0.001]were statistically significant.patients in AS and NAVR groups had 1 case of permanent pacing after TAVI treatment.In the AS and NAVR groups,there was 1 case of permanent pacemaker implantation after TAVI.2 patients in the AS group were converted to surgical treatment,and 6 patients died.Conclusions The use of"off-label"(transfemoral)and"on-label"(transapical)TAVI devices(both from domestic sources)is safer than SAVR for the treatment of NAVR,especially in elderly and high-risk patients.Compared with patients with AS treated with TAVI,larger diameter annulas are usually selected for NAVR,with higher rates of valve migration,but overall safety and efficacy are comparable to AS.
8.Optimization of immunotherapy combination strategies for microsatellite-stable advanced colorectal cancer:a real-world study
Yue GOU ; Erya HU ; Ping LIU ; Mengsi ZENG ; Qingqing LUO ; Xiangyang ZHANG ; Changjing CAI ; Hong SHEN ; Feng ZHAO ; Shan ZENG
Chinese Journal of General Surgery 2025;34(10):2106-2118
Background and Aims:Microsatellite-stable(MSS)colorectal cancer(CRC)generally exhibits poor responsiveness to immune checkpoint inhibitors(ICIs),and effective immunotherapy strategies remain lacking.Anti-angiogenic agents such as bevacizumab(BEV)can improve the tumor immune microenvironment and act synergistically with ICIs.This multicenter real-world study compared the efficacy of different immunotherapy-based combination regimens in patients with MSS/MSI-L/pMMR advanced CRC,aiming to identify the optimal treatment strategy.Methods:A total of 100 patients with MSS/MSI-L/pMMR advanced CRC who received systemic treatment between November 2019 and February 2025 at four tertiary hospitals in Hunan,China,were retrospectively enrolled.Patients were classified into six treatment groups:chemotherapy alone,chemotherapy+targeted therapy,immunotherapy alone,immunotherapy+chemotherapy,immunotherapy+targeted therapy,and immunotherapy+chemotherapy+targeted therapy.The primary endpoints were overall survival(OS)and progression-free survival(PFS),while secondary endpoints were objective response rate(ORR)and disease control rate(DCR).Additionally,among patients receiving immunotherapy,subgroup analysis was performed according to BEV administration.Results:Among all 100 patients,the immunotherapy+chemotherapy+targeted therapy group achieved the highest ORR(32.0%)and DCR(76.0%)and was the only regimen yielding a complete response(CR).Compared with chemotherapy or immunotherapy alone,the triplet regimen significantly improved OS(P<0.05);although PFS improvement did not reach statistical significance,a clear late-stage separation of survival curves was observed.In the immunotherapy subgroup,BEV-containing regimens achieved markedly better outcomes than non-BEV regimens,with DCR of 75.0%vs.48.8%,median OS of 18.9 vs.11.5 months,and median PFS of 13.8 vs.7.2 months(all P<0.001).Cox regression analysis showed that compared with chemotherapy alone,the triplet regimen significantly reduced the risk of death(HR=0.11)and disease progression(HR=0.25)(both P=0.002).Vascular invasion was identified as an adverse prognostic factor for PFS(HR=3.0,P=0.007).Conclusion:This multicenter real-world study demonstrated that combining immunotherapy with chemotherapy and targeted therapy significantly improves DCR and survival outcomes in patients with MSS/MSI-L/pMMR advanced CRC,with BEV-containing triplet regimens providing the most pronounced benefit.BEV may enhance immune responsiveness by modulating the tumor microenvironment and promoting effector T-cell infiltration,offering a promising therapeutic direction for"immune-cold"CRC.Prospective randomized studies are warranted to further validate its clinical value and define appropriate patient populations.
9.The mechanism of protective effects of dexmedetomidine based on mitophagy in a broncho-pulmonary dysplasia model of mice
Yue FENG ; Wei XIANG ; Qionglin ZHOU ; Heng CAI ; Qiuyue ZHANG
Chinese Pediatric Emergency Medicine 2025;32(1):44-49
Objective:To explore the protective mechanism of dexmedetomidine (Dex) in a model of broncho-pulmonary dysplasia (BPD) in mice exposed to hyperoxia.Methods:Neonatal rats were randomly assigned to four groups:air control group,hyperoxia injury group,Dex control group,and hyperoxia+Dex group,with six animals in each group.The air control and Dex control groups were exposed to ambient air,while the hyperoxia injury and hyperoxia+Dex groups were exposed to 90% O 2.The Dex control and hyperoxia+Dex groups received daily intraperitoneal injections of Dex at a dosage of 500 μg/kg.Lung tissue samples were collected after 7 days.Histomorphological changes in lung tissue were evaluated using hematoxylin and eosin (HE) staining,and mitochondrial ultrastructural changes in type I epithelial cells of neonatal rat lung tissue were observed via transmission electron microscopy.The activity of Complex Ⅰ in neonatal rat lung tissue was assessed.The expression levels of PINK1 and Parkin in neonatal rat lung tissue were measured using quantitative PCR (qPCR).Western blot analysis was conducted to determine the protein expression levels of PINK1 and Parkin in lung tissues. Results:Under transmission electron microscopy,mitochondrial structures were intact in the lung tissues of both the air control group and the Dex control group.However,significant mitochondrial damage was observed in the hyperoxia injury group,while the hyperoxia+Dex group exhibited some relief from mitochondrial damage compared to the hyperoxia injury group.The activity of the oxidized respiratory chain Complex Ⅰ in the hyperoxia injury group was significantly lower than that in the air control group (4.824±0.804 vs.15.276±0.804, P<0.05) and the hyperoxia+Dex group(4.824±0.804 vs.9.648±0.804, P<0.05).After qPCR analysis,the expression levels of PINK1 and Parkin in the hyperoxia injury group were higher than those in the air control group(1.80±0.06 vs.1.00±0.07,2.10±0.14 vs.1.00±0.09, P<0.05),but lower than those in the hyperoxia+Dex group(1.80±0.06 vs.3.61±0.19,2.10±0.10 vs.4.24±0.43, P<0.05).Western blot analysis revealed that the expression levels of PINK1 and Parkin in the hyperoxia injury group were higher than those in the air control group(2.16±0.11 vs.1.00±0.01,3.82±0.13 vs.1.00±0.01, P<0.05),but lower than those in the hyperoxia+Dex group(2.16±0.11 vs.3.35±0.14,3.82±0.13 vs.5.48±0.15, P<0.05).There were no significant differences in mitochondrial structure integrity,Complex Ⅰ enzyme activity,or the expression levels of PINK1 and Parkin,as assessed by qPCR and Western blot analysis,between the air control and Dex control groups( P>0.05). Conclusion:Dex effectively mitigates mitochondrial ultrastructural damage in BPD model mice,enhances the activity of Complex Ⅰ in the oxidative respiratory chain,reduces mitochondrial damage,and increases the activation of the PINK1-Parkin-mediated mitophagy pathway,thereby promoting lung protection.
10.Co-Cr-Mo guided multidirectional sliding growing rod technology for the treatment of type I neurofibromatosis induced early-onset scoliosis
Feng ZHU ; Wei MEI ; Yu YUE ; Hongjie MA ; Changtao MENG ; Dongliang CAI ; Xiangjian SONG
Chinese Journal of Orthopaedics 2025;45(7):402-411
Objective:To explore the differences in clinical efficacy between Co-Cr-Mo guided multidirectional sliding growing rod technology (CMSG) and traditional growing rod in the treatment of neurofibromatosis type 1 dysplastic early-onset scoliosis.Methods:A retrospective analysis was conducted on the data of 20 patients with neurofibromatosis type 1 dysplastic early-onset scoliosis who underwent surgical treatment in the Scoliosis Department of Zhengzhou Orthopaedic Hospital Affiliated to Henan University from January 2010 to July 2022. There were 10 patients in the traditional rod group (treated with traditional growing rod surgery) and 10 patients in the CMSG group (treated with CMSG technology). All patients were ≤10 years old and had a Cobb angle ≥45°. The number of surgeries and the occurrence of complications were recorded. The Cobb angle of the main scoliotic curve, the Cobb angle of kyphosis from T 5 to T 12, and the height from T 1 to S 1 were measured from the imaging data to evaluate the correction of deformity and spinal growth. Results:There were no significant differences in age, gender, follow - up time, preoperative Cobb angle, and preoperative Cobb angle of kyphosis from T 5-T 12 between the CMSG group and the TGR group ( P>0.05). The number of surgeries 1.3±0.67 and the total medical cost 91, 100±34, 700 yuan in the CMSG group were lower than those in the TGR group (5.3±1.77 times and 155, 800±45, 900 yuan], and the differences were statistically significant ( t=6.687, P<0.001; t=3.558, P=0.002). The Cobb angles of the main curve before surgery, after the first surgery, and at the last follow - up in the CMSG group were 69.7°±17.8°, 19.8°±9.7°, and 24.4°±9.0° respectively, while those in the TGR group were 62.0°±11.1°, 32.1°±11.4°, and 33.3°±11.6° respectively. The differences in Cobb angles after the first surgery and at the last follow-up between the two groups were statistically significant ( t=2.633, P=0.017; t=2.313, P=0.033). The Cobb angles of kyphosis from T 5 to T 12 before surgery, after the first surgery, and at the last follow - up in the CMSG group were 40.0°±24.2°, 21.0°±6.0°, and 33.6°±9.3° respectively, while those in the TGR group were 31.3°±14.5°, 26.3°±10.5°, and 32.3°±17.2° respectively. There were no significant differences in the Cobb angles of kyphosis from T 5 to T 12 after the first surgery and at the last follow-up between the two groups ( t=1.383, P=0.184; t=0.243, P=0.811). The heights from T 1 to S 1 before surgery, after the first surgery, and at the last follow-up in the CMSG group were 30.5±3.4 cm, 33.7±3.3 cm, and 37.9±4.8 cm respectively, with an annual increase of 1.18±0.39 cm. The heights from T 1 to S 1 in the TGR group were 29.1±3.0 cm, 31.4±2.9 cm, and 36.3±3.5 cm respectively, with an annual increase of 1.25±0.23 cm. There was no significant difference in the annual growth height of T 1-S 1 between the two groups ( t=1.367, P=0.189). During the follow-up period, 3 patients in the CMSG group had 3 complications: 1 case of coronal plane trunk decompensation, 1 case of rod fracture, and 1 case of distal junctional kyphosis. In the TGR group, 7 patients had 8 complications: 2 cases of wound rupture, 3 cases of screw loosening, 1 case of distal addition phenomenon, 1 case of proximal addition phenomenon, and 1 case of rod fracture. Conclusion:The Co-Cr-Mo guided multidirectional sliding growing rod technique is safe and effective in treating type 1 neurofibromatosis with malnutrition type early-onset scoliosis. It can effectively control the progression of spinal deformities,preserve the growth ability of the spine, and have a low overall incidence of complications.

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