1.Mechanisms of reproductive toxicity and ferroptosis induced by polystyrene microplastics in male mice
Jiabo WANG ; Rong LI ; Setiniaz NAZIRA ; Chengqing LIU ; Nan YANG ; Qi YAN
Journal of Environmental and Occupational Medicine 2025;42(2):224-231
Background Polystyrene microplastics (PS-MPs) attract widespread public attention due to their adverse effects on mammalian reproductive systems. However, it is currently unclear whether ferroptosis is related to testicular damage and decreased sperm quality in mice exposed to PS-MPs. Objective To clarify the reproductive damage in male mice exposed to PS-MPs and investigate the mechanism of ferroptotic effects. Methods Five-week-old male BALB/c mice were randomly divided into four experimental groups, including one control group and three PS-MPs groups at low dose (0.5 mg·kg−1), medium dose (5 mg·kg−1), and high dose (50 mg·kg−1), respectively, with 6 mice in each group. The treatment was delivered by gavage for 35 consecutive days (one time per day). After the mice were neutralized, the wet weights of testis and epididymis were measured, and organ coefficients were then calculated. Sperm was counted by hematimetry, and sperm motility and adenosine triphosphate (ATP) level were evaluated using CCK-8 and CellTiter Glo ® Kit 2.0 Assay respectively. In addition, serum testosterone, follicle-stimulating hormone, and luteinizing hormone were determined using ELISA kit, total testicular iron content was measured using tissue iron kit, and pathological changes in testicular tissue were observed after hematoxylin-eosin (HE) staining. We also used glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) assays to examine their changes to better understand the physiological status of testicular tissue. Finally, the expression levels of ferroptosis-associated proteins glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were detected by Western blotting. Results Compared with the control group, the testicular index in the high dose group decreased, and the epididymal index decreased in all dose groups (P<0.05). The results of sperm quality analysis showed that the sperm count in each dose group was lower than that of the control group; the sperm motility decreased, sperm malformation rate increased, and ATP level in sperm decreased in the medium and high dose groups. The results of HE staining showed that the spermatogenic epithelium was disordered and the arrangement of spermatogenic cells were loose in the low dose group, the spermatogenic gap was enlarged in the middle dose group, and the cells in the high dose group were vacuolated and even azoospermic. The results of serum sex hormone levels showed that the serum testosterone levels decreased in each dose group, the serum follicle-stimulating hormone levels decreased in the medium and high dose groups, and the serum luteinizing hormone levels decreased in the high dose group (P<0.05). The iron content in the testicular tissue homogenate of the high dose group increased (P<0.05). The levels of GSH and SOD in the homogenate of testicular tissue decreased in the medium and high dose groups, while the levels of MDA increased (P<0.05). The results of Western blotting showed that the protein expression level of GPX4 in the testis in the high dose group was lower than that in the control group. The protein expression levels of SLC7A11 in the medium and high dose groups were lower than that in the control group. The results of correlation analysis showed that the expression level of GPX4 was positively correlated with sperm count, and negatively correlated with MDA level (P<0.05). SLC7A11 expression level was positively correlated with sperm count, and negatively correlated with sperm malformation rate and MDA level (P<0.05). Conclusion PS-MPs exposure leads to decreased sperm quality, testicular damage, and decreased serum sex hormone levels in male mice, and its mechanism of action may involve ferroptosis.
2.Establishment of a Gastrointestinal-Brain Inter-Organ Multimodal Characterization System Based on Traditional Chinese Medicine Theory and Its Application in Refractory Diseases
Guanghui HAN ; Yan GUO ; Peijing RONG ; Bin CONG ; Shuangjiang LIU ; Shaoyuan LI ; Wei WEI
Journal of Traditional Chinese Medicine 2025;66(6):561-568
The concept of holism is the core idea of traditional Chinese medicine (TCM). Various organs and tissues coordinate with each other to maintain the body's life activities, with a close and mutual influence between the spleen, stomach, and the central nervous system (brain). The gut-brain axis plays an important bridging role between the digestive system and the central nervous system, achieving bidirectional information exchange between the brain and the gastrointestinal tract through complex neuroendocrine and immune mechanisms. The theory of cross-organ interaction involves the mutual influence, coordination, and integration between different organs and systems; multimodality, on the other hand, utilizes multiple sensory modalities, such as vision, hearing, and touch, to convey information. By combining TCM theory with the gut-brain axis theory, a cross-organ multimodal characterization system is established to explore its mechanism and application value in refractory diseases such as functional gastrointestinal disorders, precancerous gastrointestinal diseases, Alzheimer's disease, Parkinson's syndrome, type 2 diabetes, and depression.
3.Residual Inflammatory Risk and Intracranial Atherosclerosis Plaque Vulnerability: Insights From High-Resolution Magnetic Resonance Imaging
Ying YU ; Rongrong CUI ; Xin HE ; Xinxin SHI ; Zhikai HOU ; Yuesong PAN ; Mingyao LI ; Jiabao YANG ; Zhongrong MIAO ; Yongjun WANG ; Rong WANG ; Xin LOU ; Long YAN ; Ning MA
Journal of Stroke 2025;27(2):207-216
Background:
and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS).
Methods:
This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement.
Results:
Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage.
Conclusion
In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.
4.Residual Inflammatory Risk and Intracranial Atherosclerosis Plaque Vulnerability: Insights From High-Resolution Magnetic Resonance Imaging
Ying YU ; Rongrong CUI ; Xin HE ; Xinxin SHI ; Zhikai HOU ; Yuesong PAN ; Mingyao LI ; Jiabao YANG ; Zhongrong MIAO ; Yongjun WANG ; Rong WANG ; Xin LOU ; Long YAN ; Ning MA
Journal of Stroke 2025;27(2):207-216
Background:
and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS).
Methods:
This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement.
Results:
Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage.
Conclusion
In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.
5.Residual Inflammatory Risk and Intracranial Atherosclerosis Plaque Vulnerability: Insights From High-Resolution Magnetic Resonance Imaging
Ying YU ; Rongrong CUI ; Xin HE ; Xinxin SHI ; Zhikai HOU ; Yuesong PAN ; Mingyao LI ; Jiabao YANG ; Zhongrong MIAO ; Yongjun WANG ; Rong WANG ; Xin LOU ; Long YAN ; Ning MA
Journal of Stroke 2025;27(2):207-216
Background:
and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS).
Methods:
This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement.
Results:
Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage.
Conclusion
In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.
6.Regulating PI3K/Akt Signaling Pathway by Traditional Chinese Medicine to Improve Cognitive Impairment: A Review
Feifei LIU ; Yan ZHONG ; Liping CHEN ; Xiwen CHANG ; Wenbing LI ; Rong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):281-289
Cognitive impairment refers to the abnormality of the hippocampus, cortex and other parts of the brain, which is manifested by the decline of cognitive abilities such as learning, memory and attention. With the increase in people's work pressure and bad living habits, the incidence of cognitive impairment is getting higher and higher, which seriously affects people's normal life. However, there are adverse reactions such as gastrointestinal reactions and extrapyramidal reactions in Western drug treatment for cognitive impairment. Therefore, the development of a drug with relatively minimal adverse reactions is of great significance. Traditional Chinese medicine (TCM) has the characteristics of "multi-component, multi-pathway and multi-target", and the incidence of adverse reactions is relatively low. Studies have shown that the pathogenesis of cognitive impairment is closely related to oxidative stress, inflammation, apoptosis, autophagy and other processes of neurons in the cerebral cortex and hippocampus. Phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signal pathway plays an important role in the transmission of intracellular and intracellular signals, and in the regulation of cellular inflammation, apoptosis, autophagy, etc. TCM monomers, TCM extracts, and TCM compounds exert anti-inflammatory, antioxidant, anti-apoptotic and autophagy regulation effects by regulating the PI3K/Akt signaling pathway to improve cognitive impairment. This review first summarized the composition and regulatory process of the PI3K/Akt signaling pathway, and then discussed the research progress on the improvement of cognitive impairment through the improvement of oxidative stress, inflammation, apoptosis and autophagy of neurons. Finally, the recent research status of the regulation of this signaling pathway by TCM extracts, TCM monomers and TCM compounds to improve cognitive impairment was summarized. This study provides a theoretical basis for the future study of new TCM related to cognitive impairment.
7.Screening of anti-COPD quality biomarkers of Gnaphalium affine
Wanting LIU ; Rong XIE ; Dahuai LIN ; Xiangli YE ; Guohong YAN ; Huang LI
China Pharmacy 2024;35(6):683-688
OBJECTIVE To screen the quality biomarkers of Gnaphalium affine with anti-chronic obstructive pulmonary disease (COPD) effect and determine their contents. METHODS The effective components and targets of “G. affine” with anti- COPD effect were predicted by using network pharmacology as a search criterion. HPLC fingerprints for 10 batches of G. affine were established by using Similarity Evaluation System of TCM Chromatographic Fingerprint (2012 edition); common peak identification and similarity evaluation were conducted; cluster analysis (CA), principal component analysis (PCA), and orthogonal partial least squares-discriminant analysis (OPLS-DA) were performed to screen differential components as quality maker that affected the quality of G. affine using variable importance projection (VIP)>1 as the standard. The same HPLC method was adopted to determine the contents of the differential components in 10 batches of samples. RESULTS A total of 10 flavonoids (such as quercetin, luteolin, and chlorogenic acid) and organic acid components, were identified through network pharmacology search, with 91 targets closely related to anti-COPD. A total of 9 common peaks were identified in 10 batches of samples, with similarity greater than 0.90. Among them, the differential components included chlorogenic acid, caffeic acid, 1,3-O- dicaffeoylquinic acid and apigenin 7-O-β-D-glucopyranoside; S3, S4, S6, S7 and S10 were clustered into one category, S2, S5, S8 and S9 clustered into one category, and S1 clustered into one category. The contents of chlorogenic acid, caffeic acid, 1,3-O- dicaffeoylquinic acid, and apigenin 7-O-β-D-glucopyranoside in 10 batches of G. affine ranged 0.070-7.653, 0.010-0.097, 0.001- 0.036, 0.508-6.627 mg/g, respectively. CONCLUSIONS Chlorogenic acid, caffeic acid, 1,3-O-dicaffeoylquinic acid, apigenin 7- O-β-D-glucopyranoside can serve as the potential quality marker for the anti-COPD effect of G. affine, with the highest content of chlorogenic acid in G. affine produced in Ji’an, Jiangxi province, and the highest content of caffeic acid in G. affine produced in Ji’an, Jiangxi province and Sanming, Fujian province. The contents of the last two components are highest in G. affine produced in Chaoshan, Guangdong province.
8. Preparation of tripterygium glycoside nanoparticles and therapeutic effect on arthritis rats
Zhi-Rong WANG ; Man LI ; Zhen-Qiang ZHANG ; Min YAN ; Xiang-Xiang WU ; Hua-Hui ZENG
Chinese Pharmacological Bulletin 2024;40(1):125-132
Aim To prepare tripterygium glycoside nanoparticles and probe into their therapeutic effect on collagen-induced arthritis ( CIA) rats. Methods Tripterygium glycosides polyglycoside nanoparticles were prepared by thin film dispersion method and their quality was assessed. The CIA model was established and drug intervention performed. The body weight, toe swelling degree and arthritis index were measured. The pathological changes of the organs, knee and ankle synovium were observed. The serum levels of kidney function and inflammatory cytokine expression were detected in rats. Results The prepared tripterygium wil-fordii polyglycoside nanoparticles were round particles with uniform distribution and stable properties under electron microscope. Compared with the model group, the swelling of the left and right toes of medication group significantly decreased (P < 0. 01), and the ar-thritis index markedly decreased ( P < 0. 01). Among them, the efficacy of the TG-NPs group was better than that of the TG group. Compared with the normal group, the indexes of heart, spleen, kidney and testis all significantly decreased (P <0. 05, P<0.01). TG-NPs group had a significantly reduced pathological ankle-joint injury in knee cartilage and increased apoptotic synovial cells. Compared with the model group, the serum levels of ALT and BUN and CRE in TG-NPs group were significantly lower (P < 0. 05 ), and IL-1β, TNF-α and IL-6 levels decreased significantly (P <0. 05). Conclusions TG-NPs have good therapeutic effect on CIA through induction of synovial cell apoptosis and decrease of the expression of inflammatory cytokines. By intravenous injection of blood circula-tion, slow and controlled release of drugs can be achieved, the first pass effect caused by oral drug can be avoided, the viscera toxicity can be reduced, which provides an experimental basis for the development of new nanoagents for the treatment of rheumatoid arthritis.
9. Development and validation of a method for quantitation of cefepime/avibactam in M-H broth: application to antibacterial activity using in vitro PK/PD Model
Bingqian YAN ; You LI ; Miaomei TIAN ; Bingqian YAN ; Siwei GUO ; You LI ; Miaomei TIAN ; Bing XU ; Rong JIANG ; Xin LI ; Siwei GUO ; Bing XU ; Rong JIANG ; Xin LI
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(1):52-60
AIM: To establish a method for quantitation of cefepime and avibactam in M-H broth, and applicated in the in vitro dynamic PK/PD model. METHODS: The cefepime was also determined using the high-performance liquid chromatography method (HPLC), the avibactam was also determined using the liquid chromatography-mass spectrometry (LC-MS/MS), an in vitro dynamic PK/PD model was established to study the PK/PD relationship of cefepime/avibactam against carbapenem resistant Klebsiella pneumoniae (CRKP). RESULTS: The linear ranges of cefepime and avibactam were good at (0.5-20) and (0.1-25) μg/mL (r=0.999), and the lower limit concentrations were 0.5 and 0.1 μg/mL. The extraction recoveries of cefepime and avibactam in M-H broth were 88.0%-101.7% and 90.9%-95.2%, the relative standard deviation of intra-day precision and inter-day precision were less than 5.2%. The concentration-time curves were well simulated by the PK/PD model. All observed concentrations in each experiment were in the range of 20% of the targeted values. For the CRKP of MIC=8 μg/mL and MIC=16 μg/mL, the colony decreased to 2.783Log10 CFU/mL and 1.325Log10 CFU/mL at the cefepime/avibactam 2.5 g q8 h administration after 24 h. CONCLUSION: The determination method of cefepime and avibactam in broth established in this study has high sensitivity and good stability. For the CRKP with MIC≤8 μg/mL,cefepime/avibactam showed that good anti-CRKP activity under routine administration in vitro dynamic PK/PD model.
10.Value of transvaginal ultrasound combined with 3.0T magnetic resonance imaging for the diagnosis of ectopic pregnancy
Jianguo LI ; Rong LI ; Daibin JIANG ; Lamei YANG ; Yan TAN ; Yuan TU
Chinese Journal of Radiological Health 2024;33(2):195-199
Objective To compare the value of transvaginal ultrasound, 3.0T magnetic resonance imaging (MRI) scanning alone and in combination for diagnosis of ectopic pregnancy, so as to provide insights into early screening of ectopic pregnancy. Methods This study enrolled a total of 130 patients with suspected ectopic pregnancy admitted to Dachuan People’s Hospital in Dazhou City, Sichuan Province, China between February 2019 and December 2022. All patients underwent transvaginal ultrasound examination and 3.0T MRI scanning. The consistency of transvaginal ultrasound and 3.0T MRI with clinical diagnostic results was evaluated with surgical pathology or clinical follow-up results as the golden standards. The sensitivity, specificity, and accuracy of transvaginal ultrasound and 3.0T MRI, alone and in combination, were compared for diagnosis of ectopic pregnancy. Results Of the 130 patients with suspected ectopic pregnancy, 108 cases were confirmed with ectopic pregnancy by surgical pathology, and 22 cases were confirmed without ectopic pregnancy by clinical follow-up. The sensitivity, specificity, and accuracy of transvaginal ultrasound were 85.19% (92/108), 54.55% (12/22), and 80.00% (104/130), respectively, with 0.358 consistency with clinical diagnostic results. The sensitivity, specificity, and accuracy of 3.0T MRI were 92.59% (100/108), 81.81% (18/22), and 90.77% (118/130), respectively, with 0.694 consistency with clinical diagnostic results. The sensitivity, specificity, and accuracy of transvaginal ultrasound combined with 3.0T MRI were 98.15% (106/108), 72.73% (16/22), and 93.85% (122/130), respectively, with 0.764 consistency with clinical diagnostic results. In addition, the sensitivity and accuracy of transvaginal ultrasound combined with 3.0T MRI were significantly higher than transvaginal ultrasound alone for diagnosis of ectopic pregnancy (χ2 = 11.88 and 10.96, both P < 0.01). Conclusion Transvaginal ultrasound combined with 3.0T MRI may provide more diagnostic information for ectopic pregnancy, and is highly consistent with the clinical diagnostic results. In addition, transvaginal ultrasound combined with 3.0T MRI improves the diagnostic sensitivity and accuracy for ectopic pregnancy than transvaginal ultrasound alone.

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