1.Identification and Analysis of bHLH Genes Related to Color Formation of Gastrodia elata Stem
Xue JIANG ; Dandan RAN ; Xiuwen WANG ; Xiaobo ZHANG ; Xiaohong OU ; Jie PAN ; Tao ZHOU ; Zhen OUYANG ; Jiao XU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):202-209
ObjectiveGastrodia elata has evolved ecological types with shortened rhizome internodes and diversified flower and fruit coloration in response to different altitudes. Studying the genetic mechanisms of different ecotype germplasm is significant for guiding variety breeding in different cultivation areas. MethodsThe bHLH gene family was identified based on the whole-genome datasets of G. elata f. elata and G. elata f. glauca. Subsequently, the gene family members were subject to analysis, including gene structure, chromosomal localization, cis-acting elements, gene synteny, and phylogeny. Combined with transcriptome data and quantitative Real-time PCR, the expression patterns of bHLH genes in the stems of the different G. elata ecotype germplasm were analyzed. Finally, correlation analysis was conducted between gene expression patterns and color to obtain the key bHLH genes regulating the color formation of stem. ResultsA total of 63 bHLH genes were identified in both G elata f. elata and G. elata f. glauca, unevenly distributed across 17 chromosomes and clustered into 16 subfamilies, with significant expansion in some family members. Obvious inversions of bHLH genes on the same chromosome and interchromosomal translocations were detected in the two ecotype germplasm. Among these genes, 12 bHLH genes (such as bHLH62-3 and bHLH74) were associated with the bright yellow color of G elata f. elata stem, while 9 bHLH genes (such as PIL13, UNE12, and bHLH130) were correlated with the red color of G. elata f. glauca stem. Compared to G. elata f. glauca, the bHLH48 expression level was significantly higher in flowers and scale leaves of G elata f. elata, and the bHLH62-3 expression level was significantly higher in all organs of G elata f. elata. ConclusionsFunctional pathway divergence of the bHLH family members has occurred across different chromosomes in G elata f. elata and G. elata f. glauca. Through synergism or antagonism with other genes, 21 bHLH genes participate in the coloration metabolic pathway regulation of stems, flowers, and fruits. Specifically, bHLH62-3 is involved in regulating stem color differentiation in the anthocyanin biosynthesis pathway of G. elata, thus relevant to the color formation of stem. Additionally, GebHLH48 positively regulates flowering-related pathways to promote the early-flowering phenotype of G. elata f. elata. These findings have laid the foundation for analyzing the genetic regulatory mechanisms underlying the color formation of the G. elata stem.
2.Identification and Analysis of bHLH Genes Related to Color Formation of Gastrodia elata Stem
Xue JIANG ; Dandan RAN ; Xiuwen WANG ; Xiaobo ZHANG ; Xiaohong OU ; Jie PAN ; Tao ZHOU ; Zhen OUYANG ; Jiao XU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):202-209
ObjectiveGastrodia elata has evolved ecological types with shortened rhizome internodes and diversified flower and fruit coloration in response to different altitudes. Studying the genetic mechanisms of different ecotype germplasm is significant for guiding variety breeding in different cultivation areas. MethodsThe bHLH gene family was identified based on the whole-genome datasets of G. elata f. elata and G. elata f. glauca. Subsequently, the gene family members were subject to analysis, including gene structure, chromosomal localization, cis-acting elements, gene synteny, and phylogeny. Combined with transcriptome data and quantitative Real-time PCR, the expression patterns of bHLH genes in the stems of the different G. elata ecotype germplasm were analyzed. Finally, correlation analysis was conducted between gene expression patterns and color to obtain the key bHLH genes regulating the color formation of stem. ResultsA total of 63 bHLH genes were identified in both G elata f. elata and G. elata f. glauca, unevenly distributed across 17 chromosomes and clustered into 16 subfamilies, with significant expansion in some family members. Obvious inversions of bHLH genes on the same chromosome and interchromosomal translocations were detected in the two ecotype germplasm. Among these genes, 12 bHLH genes (such as bHLH62-3 and bHLH74) were associated with the bright yellow color of G elata f. elata stem, while 9 bHLH genes (such as PIL13, UNE12, and bHLH130) were correlated with the red color of G. elata f. glauca stem. Compared to G. elata f. glauca, the bHLH48 expression level was significantly higher in flowers and scale leaves of G elata f. elata, and the bHLH62-3 expression level was significantly higher in all organs of G elata f. elata. ConclusionsFunctional pathway divergence of the bHLH family members has occurred across different chromosomes in G elata f. elata and G. elata f. glauca. Through synergism or antagonism with other genes, 21 bHLH genes participate in the coloration metabolic pathway regulation of stems, flowers, and fruits. Specifically, bHLH62-3 is involved in regulating stem color differentiation in the anthocyanin biosynthesis pathway of G. elata, thus relevant to the color formation of stem. Additionally, GebHLH48 positively regulates flowering-related pathways to promote the early-flowering phenotype of G. elata f. elata. These findings have laid the foundation for analyzing the genetic regulatory mechanisms underlying the color formation of the G. elata stem.
3.Effect of mesaconate combined with LR on prolonging the golden treatment time window and its resuscitation efficacy for hemorrhagic shock rats under high-altitude conditions
Yuanqun ZHOU ; Xinming XIANG ; Xingnan OUYANG ; Jie ZHANG ; Qinghui LI ; Liangming LIU ; Tao LI
China Pharmacy 2026;37(6):720-726
OBJECTIVE To observe the effects of endogenous metabolite mesaconate combined with Sodium lactate Ringer’s injection (LR) on prolonging the golden treatment time window and its resuscitation efficacy in rats with hemorrhagic shock under high-altitude conditions. METHODS Rats were divided into the shock group, LR group, and 5, 20, 50 mg/kg mesaconate+LR groups, with 20 rats in each group, to investigate the effect of additional use of mesaconate on the golden treatment time window. After establishing a model of uncontrolled hemorrhagic shock under high-altitude conditions in all groups by housing in a hypobaric hypoxia chamber combined with splenic artery transection, rats in the shock group received no resuscitation, while rats in the LR group and mesaconate+LR groups underwent low-pressure resuscitation with LR or mesaconate combined with LR. Blood pressure control, fluid infusion volume, blood loss rate and survival status were observed in each group. Rats were further divided into the normal group, shock group and mesaconate (50 mg/kg)+LR group, with 10 or 20 rats in each group, to evaluate the resuscitation effects after extending the golden treatment time window by additionally using mesaconate. Except for the normal group, the other groups underwent the same procedure to establish an uncontrolled hemorrhagic shock model under high-altitude conditions. Rats in the shock group received no resuscitation. In the mesaconate+LR group, after 3 h of low-pressure resuscitation, bleeding control was performed by ligation of the spleen artery, and the infusion volume and blood loss rate were recorded; subsequently, the rats received LR resuscitation with twice the volume of blood loss. Then, blood gas indicators of the mesaconate+LR group were measured at different time points. Survival rates, indicators related to sublingual microcirculatory perfusion, liver and kidney blood flow, indicators related to the function of vital organs, and lung and brain water content were observed in all groups. RESULTS LR infusion alone could effectively maintain mean arterial pressure (MAP) within 50-60 mmHg for approximately 1 h. The administration of mesaconate combined with LR during hypotensive resuscitation could maintain MAP within 50-60 mmHg for over 3 h, with significantly reduced fluid infusion volume and blood loss rate in 50 mg/kg mesaconate+LR group, compared to the LR group ( P <0.05). In the LR group, rats maintained low pressure for up to 1 hour with a survival rate of 52.94%, and no rats survived beyond 2 h. In the 5, 20 and 50 mg/kg mesaconate+LR groups, rats maintained low pressure for up to 1 h with a survival rate exceeding 80%; in the 20 and 50 mg/kg mesaconate+LR groups, rats maintained low pressure for up to 3 h with a survival rate exceeding 70%. After complete resuscitation with mesaconate combined with LR, the 72 h survival rate of rats was 43.75%, and significant improvements in blood gas parameters were observed compared to the end of the shock phase ( P <0.05). Compared to the shock group, the mesaconate+LR group showed significant recovery in sublingual microcirculatory indicators, and liver/kidney blood flow after complete resuscitation ( P <0.05), with significant reductions in heart, liver and kidney function-related indicators and lung water content ( P <0.05). CONCLUSIONS Mesaconate combined with LR significantly extends the golden treatment time window for hemorrhagic shock in rats under high-altitude conditions, improves blood gas parameters, sublingual microcirculatory perfusion, and liver/kidney blood flow, mitigates vital organ impairment and pulmonary edema, and increases the survival rate of shocked rats.
4.Phase Ⅲ, multicenter, randomized comparative study of LY01005 and Zoladex ? for patients with premenopausal breast cancer
Xiying SHAO ; Qingyuan ZHANG ; Zhaofeng NIU ; Man LI ; Jingfen WANG ; Zhanhong CHEN ; Ruizhen LUO ; Guangdong QIAO ; Jianguo WANG ; Liyuan QIAN ; Ronghua YANG ; Zhendong CHEN ; Jian WANG ; Yumin YAO ; Jianghua OU ; Tao SUN ; Qiao CHENG ; Yongsheng WANG ; Jian HUANG ; Hongying ZHAO ; Wuyun SU ; Zhong OUYANG ; Yu DING ; Lilin CHEN ; Sumei YANG ; Mengsheng CUI ; Aimin ZANG ; Enxiang ZHOU ; Peizhi FAN ; Jing ZHANG ; Qiang LIU ; Yuee TENG ; Hui LI ; Jianyun NIE ; Jin YANG ; Xiaojia WANG ; Zefei JIANG
Chinese Journal of Oncology 2025;47(4):340-348
Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.
5.CT and MRI findings of mucosa-associated lymphoid tissue lymphoma of salivary gland
Yujie OUYANG ; Qifan MA ; Gongxin YANG ; Chunye ZHANG ; Xiaofeng TAO ; Ying YUAN
Journal of Practical Radiology 2025;41(2):202-205
Objective To explore the CT and MRI manifestation of salivary gland mucosa-associated lymphoid tissue(MALT)lymphoma.Methods The preoperative CT and MRI images of 89 patients with salivary gland MALT lymphoma who were confirmed by surgical pathology were analyzed retrospectively.Results Salivary gland MALT lymphoma were mainly located in the parotid gland(64 cases,71.9%).The ratio of male to female was 1 ≤ 5.Sixty-nine cases(77.5%)showed concomitant Sjogren's syndrome(SS).Typical imaging findings were round or lobulated well-marginated solid masses with moderate to severe enhancement.Atypical imaging findings were all from parotid gland MALT lymphoma,including cyst-solid mixed masses(34 cases,38.2%),poorly marginated boundaries(9 cases,10.1%),and punctuate calcification(5 cases,5.6%).The average apparent diffusion coefficient(ADC)value of lesions was(0.59±0.09)× 10-3 mm2/s and the time-signal intensity curve(TIC)type was mainly type Ⅱ(66.7%).Conclusion Salivary gland MALT lymphoma exhibits certain clinical and imaging characteristics.But when occur in parotid gland,some lesions may present atypically,which require diagnosis with the aid of functional MRI.
6.The characteristics and associated factors of hand dysfunction in patients with rheumatoid arthritis
Yaowei ZOU ; Ying YANG ; Zhiming OUYANG ; Jie PAN ; Peiwen JIA ; Kuimin YANG ; Huwei ZHENG ; Tao WU ; Jianzi LIN ; Jianda MA ; Yingqian MO ; Lie DAI
Chinese Journal of Internal Medicine 2025;64(2):119-127
Objective:To investigate the characteristics of hand dysfunction and its associated factors in patients with rheumatoid arthritis (RA).Methods:A cross-sectional study. Patients with RA were recruited from January 2019 to April 2024 at the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Demographic and clinical data were collected, including age, gender, active smoking, disease duration, time of morning stiffness, rheumatoid factor and anti-cyclic citrullinated peptide antibody, disease activity, radiographic indicators, and hand function assessment. Hand function was assessed by grip strength measures and self-reported items related to hand function in the Stanford Health Assessment Questionnaire. Factors related to hand function were analyzed by logistic regression analyses.Results:A total of 1 079 RA patients were recruited [mean age: (53.0±12.6) years]. Overall, 72.6% (783/1 079) patients experienced a decrease in grip strength, 57.2% (617/1 079) patients experienced a decreased grip strength in both hands, with the average grip strength of the left and right hands decreasing by 16.3% and 14.1%, respectively, compared to normal values; 39.9% (430/1 079) patients had self-reported hand dysfunction. There were 185 (17.1%) older RA patients (age ≥65 years). The proportion of older RA patients with decreased grip strength [89.7% (166/185) vs. 69.0% (617/894)] and degree of decrease in grip strength compared to normal values (left hand:-35.3%±30.6% vs. -12.3%±38.6%; right hand:-32.6%±32.3% vs. -10.3%±42.1%) were significantly higher than that in young patients, and the proportion of older patients with self-reported hand dysfunction was also significantly higher [53.0% (98/185) vs. 37.1% (332/894), all P<0.001]. Multivariate logistic regression analysis showed that pain visual analogue scale ( OR=1.375, 95% CI 1.020-1.854) was independently associated with grip strength decrease in older RA patients, while the 28-joint tender joint count ( OR=1.151, 95% CI 1.063-1.246) and provider global assessment of disease activity ( OR=1.381, 95% CI 1.171-1.628) were associated with self-reported hand dysfunction. Conclusions:Hand dysfunction is common in RA patients, especially among older RA patients, which is related to pain, joint tenderness and provider global assessment of disease activity. This result implies the importance of pain management in RA patients.
7.Therapeutic Study on The Inhibition of Neuroinflammation in Ischemic Stroke by Induced Regulatory T Cells
Tian-Fang KANG ; Ai-Qing MA ; Li-Qi CHEN ; Han GONG ; Jia-Cheng OUYANG ; Fan PAN ; Hong PAN ; Lin-Tao CAI
Progress in Biochemistry and Biophysics 2025;52(4):946-956
ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4+ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.
8.Inhibiting mitochondrial fission protects multiple organ functions in rats with concomitant explosive blast injury and hemorrhagic shock by improving microcirculation and vascular permeability
Yu ZHU ; Qinghui LI ; Yue WU ; Xiaoyong PENG ; Xingnan OUYANG ; Jie ZHANG ; Liangming LIU ; Tao LI
Journal of Army Medical University 2025;47(21):2581-2590
Objective To investigate the protective effect of mitochondrial fission inhibitor 1(Mdivi-1),on organ function in rats with explosive blast injury combined with hemorrhagic shock.Methods A total of 192 SD rats(half male and half female,12 weeks old,weighing about 220 g)were randomly divided into 6 groups:Sham group(only surgical incision along the midline of the abdomen),model group(ESH group,thermal radiation and shock wave injury followed by femoral artery hemorrhage),lactated Ringer's solution resuscitation group(ESH+LR group,LR solution infusion in the femoral vein for resuscitation),and low-,middle-and high-dose Mdivi-1 groups(0.1,0.5 and 1.0 mg/kg Mdivi-1 intervention after infusion of LR solution).Fluorescent protein tracing was used to determine the leakage amount of fluorescent protein in the lung and kidney tissues to evaluate the vascular permeability.Evans blue dye staining was employed to observe the intestinal permeability and pulmonary vascular permeability.Laser Doppler flowmetry was applied to monitor the tissue blood perfusion in the liver,kidneys,and intestine.Serum levels of cardiac injury marker troponin I(TNI),liver function markers aspartate aminotransferase(AST)and alanine aminotransferase(ALT),and renal function markers serum creatinine(Scr)and blood urea nitrogen(BUN)were detected to evaluate the functions of corresponding organs.The water contents of the lungs and brain were calculated by measuring wet weight and dry weight of the lung and brain tissues.Blood pressure,heart rate,and respiratory rate were monitored.The survival time and 72-hour survival rate were recorded and calculated.Results Compared with the Sham group,the ESH group exhibited significantly increased vascular permeability in the lungs and kidneys as well as intestinal tissue(P<0.05),along with obviously elevated water contents in the lungs and brain(P<0.05),and decreased blood perfusion in the liver,kidneys,and intestine by 57.1%,39.2%,and 43.2%of the Sham group,respectively(P<0.05),elevated levels of TNI,AST,ALT,Scr and BUN(P<0.05),mean survival time of 3.8±1.1 h,and a 72-hour survival rate of 0(P<0.05).Although LR solution resuscitation reduced vascular permeability and alleviated organ injury in rats with explosive injury combined with hemorrhagic shock,there were no significant differences compared to the ESH group(P>0.05).Mdivi-1 treatment notably decreased vascular permeability in the lungs and kidneys and intestine,and water contents in the lungs and brain when compared with the LR group(P<0.05),with the dose of 0.5 mg/kg demonstrating the most significant effect.Additionally,Mdivi-1 treatment also significantly enhanced organ perfusion,improved organ functions,prolonged survival time,and increased survival rate.The 0.5 mg/kg treatment resulted in a 72-hour average survival time 55.64 h and a survival rate of 62.5%.Conclusion Mitochondrial fission inhibitor Mdivi-1 can reduce the permeabilities in the lungs,kidneys and intestine,improve tissue blood perfusion,protect the organ functions of the heart,liver and kidneys,and finally prolong survival time and increase survival rate in rats with concomitant explosive blast injury and hemorrhagic shock.
9.Effect and underlying mechanism of L-carnitine improving myocardial systolic dysfunction in sepsis mice
Zhihua WANG ; Yuanqun ZHOU ; Xinming XIANG ; Qianwei ZHANG ; Xingnan OUYANG ; Jie ZHANG ; Tao LI ; Linqiang TIAN ; Liangming LIU
Journal of Army Medical University 2025;47(21):2630-2640
Objective To explore the protective effect of L-carnitine on myocardial systolic dysfunction in sepsis and its underlying mechanism.Methods A mouse sepsis model was established by cecal ligation and puncture(CLP).Ten-week-old male SPF-grade C57BL/6 mice(body weight 20~30 g)were randomly divided into 5 groups via random number table:Sham group,Sepsis group,L-carnitine group,L-carnitine+Etomoxir(Eto)group,and Eto group.Echocardiography assessed cardiac function,ELISA measured serum creatine kinase isoenzyme MB(CK-MB)levels,and 72-hour survival rates were recorded to evaluate L-carnitine's effects on cardiac function.Cardiomyocytes were isolated,and a cell microtensiometer was used to detect cardiomyocyte contractile function and calcium transients.Myocardial tissues were collected from each group,and ELISA was used to determine the contents of triglyceride(TG),free fatty acid(FFA),and adenosine triphosphate(ATP).An in vitro sepsis model was constructed by stimulating HL-1 cardiomyocytes with lipopolysaccharide(LPS)for 12 hours,which was divided into 5 groups:control(CTRL)group,LPS group,L-carnitine group,L-carnitine+Eto group,and Eto group.ELISA was used to detect the contents of TG,FFA,and ATP as well as the activity of carnitine palmitoyltransferase 1A(CPT1A)in cardiomyocytes.A cellular energy metabolism analysis system was employed to measure fatty acid oxidation capacity,and Western blot was used to detect the protein expression of CPT1A in cardiomyocytes.BODIPY-FL-C16(green fluorescently labeled palmitic acid)was utilized to detect the distribution of fatty acids in the cytoplasm and mitochondria via immunofluorescence technology,thereby observing the ability of cells to transport fatty acids into mitochondria.Results Compared with the Sham group,cardiac function was significantly impaired in the Sepsis group,as evidenced by decreased ejection fraction and mean arterial pressure(P<0.05),along with elevated levels of the cardiac injury marker CK-MB(P<0.05).Treatment with L-carnitine significantly improved myocardial function,restored blood pressure in septic mice,and increased their survival rate from 12.50%to 81.25%(P<0.05).Compared with the Sham group,the contractile function and calcium transients of acutely isolated single cardiomyocytes were significantly reduced in the Sepsis group(P<0.05),while L-carnitine treatment remarkably restored the contractile function and calcium release capacity of septic cardiomyocytes(P<0.05).Both in vivo and in vitro experiments showed that TG and FFA levels were significantly increased(P<0.05),and ATP levels was significantly decreased(P<0.05)in the Sepsis and LPS groups—effects significantly reversed by L-carnitine treatment.Compared with the CTRL group,the basal oxidation rate and maximum oxidation capacity of fatty acids in cardiomyocytes of the LPS group were significantly reduced(P<0.05),and L-carnitine treatment notably improved these indicators.Compared with the CTRL group,the expression and activity of CPT1A in cardiomyocytes of the LPS group were significantly decreased(P<0.05),while L-carnitine treatment significantly increased the expression and activity of CPT1A(P<0.05).In LPS group cardiomyocytes,green fluorescently labeled palmitic acid primarily formed numerous granular/clumpy aggregates in the cytoplasm with minimal mitochondrial colocalization.In the L-carnitine group,the green fluorescent granules in the cytoplasm of cardiomyocytes were smaller,and colocalization with mitochondria was increased.However,the L-carnitine+Eto group exhibited similar phenomena to the LPS group.In addition,both in vivo and in vitro experiments demonstrated that treatment with the CPT1A inhibitor Eto reversed the effect of L-carnitine.Compared with the L-carnitine group,the ATP content in the L-carnitine+Eto group was significantly decreased(P<0.05),while the FFA content was significantly increased(P<0.05).Conclusion L-carnitine facilitates fatty acid entry into mitochondria for β-oxidation via a CPT1A-dependent mechanism,thereby ameliorating fatty acid oxidation dysfunction in septic cardiomyocytes and improving myocardial contractile function.
10.The value of phase-resolved functional lung MRI in the quantitative assessment of pulmonary perfusion and ventilation defects in restrictive ventilatory dysfunction
Tao OUYANG ; Hongjie CAO ; Qi YANG
Chinese Journal of Radiology 2025;59(7):757-764
Objective:To investigate the value of phase-resolved functional lung MRI (PREFUL-MRI) in identifying pulmonary perfusion and ventilation defects in patients with restrictive ventilatory dysfunction (RVD).Methods:This study was a cross-sectional study. Participants were prospectively enrolled from March 2023 to July 2024 at Beijing Chaoyang Hospital, Capital Medical University, where they underwent pulmonary function testing [indicators including first second forced expiratory volume (FEV 1), forced vital capacity(FVC), FVC percent predicted(FVC%pred), FEV 1 percent predicted(FEV 1%pred),et al] and low-dose CT examinations. Based on pulmonary function results, all participants were divided into an RVD group and a control group. The RVD group was further subdivided into a mild RVD subgroup (FEV 1%pred≥70%) and a moderate-to-severe RVD subgroup (FEV 1%pred<70%). All participants underwent PREFUL-MRI examination. Quantitative lung perfusion parameters were measured, including perfusion quantified (Q Quantified) and perfusion defect percentage (QDP). Ventilation parameters were also acquired, including regional ventilation (RVent), flow-volume loop correlation metric (FVL-CM), and ventilation defect percentages (VDP RVent and VDP FVL-CM). Comparisons of continuous variables between groups were performed using the Mann-Whitney U test, while categorical variables were compared using the χ2 test or Fisher′s exact test. Spearman correlation analysis was used to assess the relationships between pulmonary function parameters and lung perfusion and ventilation parameters. Variables showing statistically significant differences between the RVD and control groups, or between the mild and moderate-to-severe RVD subgroups in univariate analyses, were included in multivariate binary logistic regression analysis to identify independent risk factors for the occurrence of RVD and moderate-to-severe RVD, and predictive models were constructed. The predictive performance of the models was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Results:A total of 37 patients were included in the RVD group (23 males and 14 females), with a median age of 59 (52, 75)years. Among them, 18 had mild RVD and 19 had moderate-to-severe RVD. The control group consisted of 49 individuals (39 males and 10 females), with a median age of 55(46.5, 60) years. The RVD group had lower FEV 1%pred, FVC%pred, and Q Quantified, and higher RVent and QDP compared to the control group ( P<0.05). The moderate-to-severe RVD subgroup had lower FEV 1%pred, FVC%pred, and Q Quantified, and higher RVent and QDP than the mild RVD subgroup ( P<0.05). In the RVD group, FEV 1%pred and FVC%pred showed significant positive correlations with RVent and Q Quantified, and significant negative correlations with QDP ( P<0.05). The FEV 1/FVC ratio was positively correlated with RVent and FVL-CM, and negatively correlated with VDP RVent, VDP FVL-CM, and QDP ( P<0.05). Logistic regression analysis revealed that Q Quantified ( OR=0.97, 95% CI 0.94-0.99, P=0.005) and QDP ( OR=1.23, 95% CI 1.07-1.41, P=0.003) were independent predictors of RVD, and the AUC of the predictive model was 0.823. QDP ( OR=1.23, 95% CI 1.07-1.41, P=0.003) was identified as an independent predictor of moderate-to-severe RVD, with the model achieving an AUC of 0.825. Conclusions:PREFUL-MRI facilitates the noninvasive assessment of pulmonary perfusion abnormalities in RVD. The quantitative perfusion parameter serves as a valuable biomarker for detecting RVD and evaluating its severity, offering a novel tool for both pathophysiological research and clinical assessment.

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