1.Supramolecular prodrug inspiried by the Rhizoma Coptidis - Fructus Mume herbal pair alleviated inflammatory diseases by inhibiting pyroptosis.
Wenhui QIAN ; Bei ZHANG ; Ming GAO ; Yuting WANG ; Jiachen SHEN ; Dongbing LIANG ; Chao WANG ; Wei WEI ; Xing PAN ; Qiuying YAN ; Dongdong SUN ; Dong ZHU ; Haibo CHENG
Journal of Pharmaceutical Analysis 2025;15(2):101056-101056
Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.
2.Coral calcium hydride promotes peripheral mitochondrial division and reduces AT-II cells damage in ARDS via activation of the Trx2/Myo19/Drp1 pathway.
Qian LI ; Yang ANG ; Qing-Qing ZHOU ; Min SHI ; Wei CHEN ; Yujie WANG ; Pan YU ; Bing WAN ; Wanyou YU ; Liping JIANG ; Yadan SHI ; Zhao LIN ; Shaozheng SONG ; Manlin DUAN ; Yun LONG ; Qi WANG ; Wentao LIU ; Hongguang BAO
Journal of Pharmaceutical Analysis 2025;15(3):101039-101039
Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.
3.Evaluation and management of nutritional consequences in patients with alcoholic cirrhosis
Lijie WANG ; Yanrong YANG ; Yu CHEN ; Jinling DONG
Journal of Clinical Hepatology 2025;41(4):761-767
Patients with alcoholic cirrhosis often experience varying degrees of malnutrition, and the patients with malnutrition are more susceptible to complications such as infections and ascites, which may lead to a poor prognosis. Therefore, it is particularly important to conduct nutritional risk screening for patients in clinical practice, and appropriate nutritional assessment tools should be used to evaluate the nutritional status of patients and develop individualized nutritional supplementation regimens, thereby promoting disease recovery and improving prognosis and quality of life. This article elaborates on the specific methods for nutritional screening, assessment, and management in patients with alcoholic cirrhosis and points out that systematic nutritional screening and assessment can help to identify the patients with malnutrition in the early stage and provide timely intervention. Individualized nutritional supplementation regimens should be adjusted based on the conditions of patients, so as to meet their nutritional needs, promote the recovery of liver function, improve overall health status, and enhance long-term quality of life.
4.Effect of Linggui Zhugantang on Ventricular Remodeling After Myocardial Infarction and RhoA/ROCK Signaling Pathway
Han REN ; Wanzhu ZHAO ; Shushu WANG ; Rui CAI ; Yuanhong ZHANG ; Shengyi HUANG ; Jinling HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):1-9
ObjectiveThis study aims to investigate the effects of Linggui Zhugantang (LGZGT) on ventricular remodeling (VR) in mice with myocardial infarction (MI) and its impact on the Ras homologgene A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway. MethodsThe MI model of mice was established by ligating the left anterior descending coronary artery (LAD). They were divided into the sham-operated group, the model group, the low-dose, medium-dose, and high-dose groups of LGZGT (2.34, 4.68, 9.36 g·kg-1), and the captopril group (3.25 mg·kg-1), with 10 mice in each group. After four weeks of continuous drug administration by gavage, the level of cardiac function in each group of mice was examined using small animal Doppler ultrasound. Hematoxylin-eosin (HE) staining and Masson staining was used to assess the morphological changes of myocardial tissue and calculate the rate of collagen fiber deposition in mouse myocardial tissue. Wheat germ agglutinin (WGA) staining was employed to compare the cross-sectional area of cardiomyocytes in each group of mice. The expression levels of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), type Ⅰcollagen (Col Ⅰ), Col Ⅲ, tissue inhibitor of metalloproteinase 1(TIMP1), B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), Bcl-2, Caspase-3, and cleaved Caspase-3 were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to evaluate the mRNA levels of the pathway-related genes RhoA, ROCK1, and ROCK2. The protein expression levels of RhoA, ROCK1, and ROCK2 were tested by Western blot. ResultsThe level of cardiac function was markedly declined in the model group compared to the sham-operated group(P<0.01). Myocardial tissue morphology changed significantly. The cross-sectional area of cardiomyocytes was significantly enlarged. The expression of α-SMA, MMP-2, Col Ⅰ, and Col Ⅲ was significantly upregulated(P<0.01), and TIMP1 protein expression was significantly reduced(P<0.01). The expressions of apoptosis-related proteins Bax were significantly up-regulated(P<0.01), while the expression of Bcl-2 protein was significantly decreased(P<0.01). The mRNA expression of RhoA, ROCK1, and ROCK2 were significantly upregulated (P<0.01). Compared to the model group, the low-dose, medium-dose, and high-dose groups of LGZGT and the captopril group significantly reversed the experimental results of the model group in a dose-dependent manner (P<0.05, P<0.01). ConclusionLGZGT significantly attenuated myocardial fibrosis, myocardial hypertrophy, and cardiomyocyte apoptosis after MI in mice and effectively reversed VR, the mechanism of which may be related to the modulation of the RhoA/ROCK signaling pathway.
5.Effect of Linggui Zhugantang on Ventricular Remodeling After Myocardial Infarction and RhoA/ROCK Signaling Pathway
Han REN ; Wanzhu ZHAO ; Shushu WANG ; Rui CAI ; Yuanhong ZHANG ; Shengyi HUANG ; Jinling HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):1-9
ObjectiveThis study aims to investigate the effects of Linggui Zhugantang (LGZGT) on ventricular remodeling (VR) in mice with myocardial infarction (MI) and its impact on the Ras homologgene A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway. MethodsThe MI model of mice was established by ligating the left anterior descending coronary artery (LAD). They were divided into the sham-operated group, the model group, the low-dose, medium-dose, and high-dose groups of LGZGT (2.34, 4.68, 9.36 g·kg-1), and the captopril group (3.25 mg·kg-1), with 10 mice in each group. After four weeks of continuous drug administration by gavage, the level of cardiac function in each group of mice was examined using small animal Doppler ultrasound. Hematoxylin-eosin (HE) staining and Masson staining was used to assess the morphological changes of myocardial tissue and calculate the rate of collagen fiber deposition in mouse myocardial tissue. Wheat germ agglutinin (WGA) staining was employed to compare the cross-sectional area of cardiomyocytes in each group of mice. The expression levels of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), type Ⅰcollagen (Col Ⅰ), Col Ⅲ, tissue inhibitor of metalloproteinase 1(TIMP1), B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), Bcl-2, Caspase-3, and cleaved Caspase-3 were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to evaluate the mRNA levels of the pathway-related genes RhoA, ROCK1, and ROCK2. The protein expression levels of RhoA, ROCK1, and ROCK2 were tested by Western blot. ResultsThe level of cardiac function was markedly declined in the model group compared to the sham-operated group(P<0.01). Myocardial tissue morphology changed significantly. The cross-sectional area of cardiomyocytes was significantly enlarged. The expression of α-SMA, MMP-2, Col Ⅰ, and Col Ⅲ was significantly upregulated(P<0.01), and TIMP1 protein expression was significantly reduced(P<0.01). The expressions of apoptosis-related proteins Bax were significantly up-regulated(P<0.01), while the expression of Bcl-2 protein was significantly decreased(P<0.01). The mRNA expression of RhoA, ROCK1, and ROCK2 were significantly upregulated (P<0.01). Compared to the model group, the low-dose, medium-dose, and high-dose groups of LGZGT and the captopril group significantly reversed the experimental results of the model group in a dose-dependent manner (P<0.05, P<0.01). ConclusionLGZGT significantly attenuated myocardial fibrosis, myocardial hypertrophy, and cardiomyocyte apoptosis after MI in mice and effectively reversed VR, the mechanism of which may be related to the modulation of the RhoA/ROCK signaling pathway.
6.DC-CIK cell as an adjuvant to cetuximab combined with CAPEOX chemotherapy regimen for the treatment of 52 cases of advanced colorectal cancer
WANG Zixuan ; JIANG Longwei ; CHEN Yitian ; JIA Shaochang
Chinese Journal of Cancer Biotherapy 2025;32(4):413-417
[摘 要] 目的:评价DC-CIK细胞免疫治疗辅助西妥昔单抗联合CAPEOX(奥沙利铂 + 卡培他滨)化疗方案治疗全RAS基因野生型、BRAF基因野生型晚期结直肠癌(CRC)的临床疗效与安全性。方法:回顾性分析2020年12月至2023年10月期间东部战区总医院肿瘤科收治的52例晚期CRC的临床资料,其中对照组与观察组分别为26例。观察组在对照组化疗基础上给予DC-CIK细胞治疗,统计患者的临床疗效和不良反应,分析患者的近期疗效、生活质量评分、化疗不良反应发生情况,以及治疗前后肿瘤标志物和免疫指标的变化。结果:与对照组相比,观察组晚期CRC患者的疾病控制率(DCR)、生活质量均明显提高(均P < 0.05),化疗后腹泻或便秘的发生率、肿瘤标志物CA72-4均明显降低(均P < 0.05),NK细胞计数明显上升(P < 0.05)。结论:在晚期CRC患者行DC-CIK细胞免疫治疗辅助西妥昔单抗联合CAPEOX化疗方案治疗安全可行,能够显著提高DCR,为患者带来显著的临床获益。
7.Value of multimodal ultrasound score for assessment of endometrial receptivity among patients with polycystic ovary syndrome
Zhihui HAN ; Shuqin FU ; Yuwei WANG ; Bin YANG
Chinese Journal of Radiological Health 2025;34(2):167-173
Objective To assess the clinical value of multimodal ultrasound score for assessment of endometrial receptivity among patients with polycystic ovary syndrome (PCOS), and to provide guidance for improving pregnancy outcomes among PCOS patients. Methods A total of 48 PCOS patients admitted to Jiangning Hospital Affiliated to Nanjing Medical University between January and December 2023 were enrolled as the case group, while 50 healthy women of childbearing age received ovulation monitoring at the same hospital during the same period served as the control group. Subjects received two-dimensional grayscale ultrasound during the implantation window (19 to 23 days of the menstrual cycle) for measurement of endometrial thickness, Gonen classification, and endometrial peristalsis. Two-dimensional color Doppler ultrasound was used for assessment of endometrial blood flow and three-dimensional ultrasound was used for assessment of endometrial volume and vascularization flow index (VFI). The endometrium multimodal ultrasound scores were estimated, and various parameters were compared between the two groups. The diagnostic performance of these parameters for PCOS was evaluated with receiver operating characteristic (ROC) curves. Results The age of subjects in the case group ranged from 20 to 38 years, with a mean age of (28.20 ± 2.82) years, and their body mass index (BMI) ranged from 21.23 to 29.11 kg/m2, with a mean BMI of (26.25 ± 1.60) kg/m2. The age of subjects in the control group ranged from 22 to 38 years, with a mean age of (28.10 ± 1.99) years, and their BMI ranged from 21.33 to 29.03 kg/m2, with a mean BMI of (26.10 ± 1.78) kg/m2. There were no significant differences between the case and control groups in terms of mean age, BMI, estradiol, and testosterone (t = 0.218, 0.422, 0.010, and 0.221; all P > 0.05). The endometrial thickness, endometrial volume, and VFI were significantly higher in the control group than in the case group (t = 4.838, 4.978, and 7.115; all P < 0.05). There were significant differences between the two groups in terms of endometrial classification, endometrial peristalsis pattern, and endometrial and sub-endometrial blood flow (Z = −4.136, −4.048, and −3.884; all P < 0.05). The scores of endometrial classification, endometrial peristalsis, endometrial and sub-endometrial blood flow, endometrial volume, VFI, and multimodal ultrasound were significantly lower in the case group than in the control group (t = 4.539, 4.449, 4.205, 3.209, 5.206, and 4.495; all P < 0.05). No significant difference was detected in the endometrial thickness score between the two groups (t = -0.149, P = 0.882). The areas under the ROC curves for endometrial thickness, endometrial volume, VFI, and multimodal ultrasound scores in diagnosis of PCOS were 0.753, 0.747, 0.809, and 0.858, respectively. Conclusion Multimodal ultrasound score provides a comprehensive assessment of the endometrium, and is effective in the assessment of endometrial receptivity, which may provide a reference for guiding pregnancy planning in PCOS patients.
8.Effect of storage conditions on long-term preservation of PRP growth factors
Qing QI ; Zhaojie LI ; Qiong WU ; Pingping MAO ; Yangzi SUN ; Jianfeng LUAN ; Shujun WANG
Chinese Journal of Blood Transfusion 2025;38(6):759-765
Objective: To compare the changes in the concentration of relevant growth factors released from platelet-rich plasma (PRP) stored at -80℃ by cryopreservation and at 4℃ by refrigerated lyophilization over 2 years, aiming to provide a theoretical basis for prolonging PRP storage duration. Methods: PRP (n=15) was separated using a blood cell separator and stored under -80℃ cryopreservation (F-PRP group) and 4℃ refrigerated freeze-drying conditions (FD-PRP group). The contents of growth factors (PDGF-AA, PDGF-BB, EGF, TGF-β1, and VEGF) in both groups were measured by ELISA at 1, 3, 6, 9, 12 and 24 months. Results: PDGF-AA and VEGF maintained good stability in both groups for up to 24 months. PDGF-BB and TGF-β1 showed high stability in the first 12 months but their stability decreased gradually from 12th to 24th months. EGF demonstrated good stability in the first 6 months, and its stability gradually decreased from the 9th to 24th months. Comparing the F-PRP and FD-PRP groups, the concentrations of the five growth factors in the FD-PRP group were either not statistically different or higher than those in the F-PRP group at all time points. Specifically, the concentrations of EGF were significantly higher in the FD-PRP group at all time points. Conclusion: Both -80℃ freezing and 4℃ freeze-drying enable long-term preservation of PRP. Freeze-drying imposes less stringent storage requirements and facilitates growth factor compared to frozen storage.
9.Establishment and evaluation of an animal model of heart failure with preserved ejection fraction integrating disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis
Xiaoqi WEI ; Xinyi FAN ; Feng JIANG ; Wangjing CHAI ; Jinling XIAO ; Fanghe LI ; Kuo GAO ; Xue YU ; Wei WANG ; Shuzhen GUO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):501-515
Objective:
This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively.
Methods:
The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model.
Results:
Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group.
Conclusion
This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.
10.A novel homozygous mutation of CFAP300 identified in a Chinese patient with primary ciliary dyskinesia and infertility.
Zheng ZHOU ; Qi QI ; Wen-Hua WANG ; Jie DONG ; Juan-Juan XU ; Yu-Ming FENG ; Zhi-Chuan ZOU ; Li CHEN ; Jin-Zhao MA ; Bing YAO
Asian Journal of Andrology 2025;27(1):113-119
Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult
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Female
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Humans
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Male
;
Pregnancy
;
China
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Ciliary Motility Disorders/genetics*
;
Codon, Nonsense
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East Asian People/genetics*
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Exome Sequencing
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Homozygote
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Infertility, Male/genetics*
;
Kartagener Syndrome/genetics*
;
Pedigree
;
Sperm Injections, Intracytoplasmic
;
Cytoskeletal Proteins/genetics*


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