1.Aerobic Exercise and MOTS-c Ameliorate Hepatic Oxidative Stress and Metabolic Disorder in Type 2 Diabetes via The NRF2/PPARγ Axis
Fei-Long CHEN ; Zhi-Yu LI ; Tu-Tu WANG ; Yu FU ; Lei LÜ ; Cheng-Yuan XING ; Shun-Chang LI
Progress in Biochemistry and Biophysics 2026;53(8):2071-2090
ObjectiveType 2 diabetes mellitus (T2DM) often causes severe hepatic metabolic complications, dominated by metabolic associated fatty liver disease (MAFLD). Persistent hepatic steatosis and oxidative stress further trigger steatohepatitis and progressive liver damage, increasing the mortality risk of diabetic patients. Aerobic exercise effectively improves hepatic lipid metabolism and antioxidant capacity, but poor patient adherence restricts its long-term clinical application. Mitochondrial-derived mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is a key peptide regulating insulin sensitivity and hepatic redox homeostasis. This study aimed to explore the protective mechanism of MOTS-c against T2DM-related liver injury and its combined beneficial effect with aerobic exercise via the NRF2/PPARγ signaling axis. This study aimed to investigate whether MOTS-c cooperates with aerobic exercise to alleviate T2DM-associated hepatic oxidative stress and metabolic dysfunction by activating the NRF2/PPARγ axis, and to clarify the molecular and transcriptomic characteristics of their combined intervention. MethodsStable MOTS-c overexpression and knockdown HepG2 cell lines were constructed using lentiviral transfection. An oleic acid-induced cellular lipid accumulation model and NRF2-knockout cell model were applied to verify the NRF2-dependent mechanism ofMOTS-c. Intracellular lipid deposition, triglyceride levels, antioxidant enzyme activities, and the expression of NRF2/PPARγ pathway-related genes and proteins were detected. In vivo, a T2DM rat model with obvious hepatic steatosis was established via a high-fat and high-sucrose diet combined with streptozotocin injection. Model rats received aerobic exercise, MOTS-c intraperitoneal injection, or combined intervention. We detected systemic glycolipid metabolic indicators, hepatic histopathological changes, and the expression of core proteins in the hepatic NRF2/PPARγ axis. Hepatic transcriptomic sequencing was performed to screen differentially expressed genes (DEGs) and enrich key pathways co-regulated by MOTS-c and aerobic exercise. ResultsCellular results showed that MOTS-c overexpression significantly reduced oleic acid-induced lipid deposition, enhanced antioxidant enzyme activity, and upregulated NRF2 and PPARγ expression. Conversely, MOTS-c knockdown aggravated hepatic lipid accumulation and oxidative damage and inhibited NRF2/PPARγ pathway activation. NRF2 knockout completely eliminated the protective effects of MOTS-c on lipid metabolism and redox balance, confirming its NRF2-dependent regulatory mechanism. In T2DM rats, both MOTS-c supplementation and aerobic exercise effectively improved insulin resistance, corrected glycolipid metabolic disorders, and alleviated hepatic steatosis, while consistently activating the hepatic NRF2/PPARγ axis. Compared with single intervention, the combined treatment showed a better improvement trend in hepatic metabolic and oxidative injury, without definitive synergistic effects. Transcriptomic analysis revealed that the co-regulated DEGs of MOTS-c and aerobic exercise were primarily enriched in lipid metabolism and PPAR signaling pathways, with multiple antioxidant and lipid-regulating genes significantly modulated by combined intervention. ConclusionMOTS-c exhibits obvious exercise-mimetic hepatoprotective effects in T2DM. It activates the hepatic NRF2/PPARγ axis to strengthen antioxidant defense, stabilize lipid metabolism, and relieve T2DM-associated hepatic steatosis and oxidative damage. Furthermore, MOTS-c produces additive beneficial effects with aerobic exercise, showing a superior intervention trend on diabetic liver dysfunction. This study identifies the NRF2/PPARγ axis as the core mechanism of MOTS-c-regulated hepatic protection, elucidates the transcriptomic basis of combined intervention, and provides a reliable theoretical basis and potential therapeutic target for clinical intervention in T2DM-complicated MAFLD.
2.Effects of electroacupuncture at acupoints of Shaoyang meridian on peripheral TRPV1 and CGRP in rats with chronic migraine
Runze TU ; Yixiang ZENG ; Shengli ZHOU ; Haojia WEN ; Yang YANG ; Zhuozhong HE ; Weiai LIU ; Ke HE ; Lei FU
International Journal of Traditional Chinese Medicine 2025;47(4):483-487
Objective:To observe the effects of electroacupuncture (EA) at acupoints of Shaoyang meridian on mechanical and thermal pain threshold, TRPV1, CGRP mRNA and TRPV1, p-TRPV1, CGRP protein expressions in TG of CM rats; To explore its mechanism.Methods:Totally 24 SD rats were divided into blank group, model group and EA group according to random number table method, with 8 rats in each group. The blank group did not do any treatment; the model group and the EA group were given intraperitoneal injection of nitroglycerin (10 mg/kg) on the 1st, 3rd, 5th, 7th and 9th day, once a day, for 5 times to prepare migraine rat model; after modeling, the model group was given binding and restraint for 30 min, and the EA group was given binding and restraint for 30 min treatment; the changes of basic mechanical and thermal pain thresholds of rats before and after modeling and intervention were observed, the mRNA expression levels of TRPV1 and CGRP in TG rats were detected by qPCR, and the protein expression levels of TRPV1, p-TRPV1 and CGRP in TG rats were detected by Western blot method.Results:After intervention, compared with the model group, the periorbital and plantar mechanical pain thresholds and plantar thermal pain thresholds in EA group increased ( P<0.05), the TRPV1 and CGRP mRNA expressions in trigeminal ganglion decreased ( P<0.01), the protein expressions of TRPV1, p-TRPV1 and CGRP decreased ( P<0.05). Conclusion:EA at acupoints of Shaoyang meridian can obviously increase the mechanical and thermal pain threshold and improve pain sensitization in CM rats. The mechanism would be related to down-regulating the expression levels of TRPV1 and CGRP mRNA and TRPV1, p-TRPV1 and CGRP protein in the TG of CM rats.
3.Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in anterior mediastinal masses
Junmin ZHU ; Junjie WANG ; Jianming YUE ; Yixin SUN ; Yichen LIU ; Lei WANG ; Lin LIN ; Jie LI ; Jinlan ZHAO ; Xuehua TU ; Ningying DING ; Jianrong HU ; Chunmei HE ; Leilei TIAN ; Hongtao TANG ; Jiasheng ZHAO ; Cheng CHEN ; Yongxiang SONG ; Yunwei TIAN ; Yong XIAO ; Kaidi LI ; Lin MA ; Yun WANG ; Longqi CHEN ; Dong TIAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(11):1603-1609
Objective To assess the clinical value of a novel surgical technique—Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in the resection of anterior mediastinal masses. Methods Patients who underwent tubeless subxiphoid uniportal video-assisted thoracoscopic surgery via balance-shaped sternal elevation device in anterior mediastinal masses process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to April 2025 were included, and their clinical data were analyzed. Results A total of 4 patients were included, with 2 males and 2 females, aged 58-75 years. The diameter of the tumor was 2.5-3.0 cm. The operation time was 60.0-150.0 min, intraoperative blood loss was 5-10 mL, pain score on the 3rd day after surgery was 0 points, and postoperative hospital stay was 2-3 days. All patients achieved complete resection of the masses and thymus without perioperative complications. Conclusion The tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device technique optimizes surgical visualization and instrument maneuverability while avoiding complications related to conventional anesthesia and tubing, thereby markedly enhancing the minimally invasive profile of anterior mediastinal masses resections. In addition to maintaining procedural safety, this approach effectively reduces postoperative pain and accelerates patient recovery, highlighting its potential for widespread clinical adoption.
4.The introduction on the new standards of pharmaceutical excipients in the Chinese Pharmacopoeia 2025 Edition
Lei CHEN ; Ying CHEN ; Jiasheng TU ; Yanming LIU ; Luxia ZHENG ; Jun ZHANG ; Shuangcheng MA
Drug Standards of China 2025;26(1):58-66
According to the work goals and tasks determined by edition outline of the Chinese Pharmacopoeia 2025 Edition,the Chinese Pharmacopoeia 2025 Edition has been completed.Among them,52 new pharmaceutical excip-ients monographs have been added,an increase of 15.5%compared with the 2020 Edition,and the total number has reached 387.This article focuses on the general framework and the main characteristics of the standards of pharmaceutical excipients in the Chinese Pharmacopoeia 2025 Edition,which can contribute to accurately under-stand and utilize the standards in Chinese Pharmacopoeia.
5.Consensus on the use of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for cancer pain management
Yi LU ; Cunzhi LIU ; Wujun GENG ; Xiaozhen ZHENG ; Jingdun XIE ; Guangfang ZHANG ; Chao LIU ; Yun LI ; Yan QU ; Lei CHEN ; Xizhao HUANG ; Hang TIAN ; Yuhui LI ; Hongxin LI ; Heying ZHONG ; Ronggui TAO ; Jie ZHONG ; Yue ZHUANG ; Junyang MA ; Yan HU ; Jian FANG ; Gaofeng ZHAO ; Jianbin XIAO ; Weifeng TU ; Jiaze SUN ; Yuting DUAN ; Bao WANG
Journal of Southern Medical University 2025;45(8):1800-1808
Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
6.Elucidating the Therapeutic Mechanism of Huanglian Zhimu Decoction in Type 2 Diabetes Mellitus Based on Gut Microbiota and Metabolomics
Lei WANG ; Wenling TU ; Lingyong CAO
Journal of Zhejiang Chinese Medical University 2025;49(6):661-673
[Objective]To investigate the mechanism of Huanglian Zhimu Decoction in treating type 2 diabetes mellitus(T2DM)rats by 16S ribosomal RNA(16S rRNA)gut microbiota gene sequencing and non-targeted metabolomics.[Methods]Twenty-four GK rats were fed a high-fat diet to induce a T2DM model.After successful modeling,they were divided into T2DM model(MO)group,Huanglian Zhimu Decoction(HL)group and metformin(MET)group.Eight Wistar rats were designated as control(CTRL)group.After 12 weeks of drug intervention,the food intake,water intake,urine volume,body weight and fasting blood glucose of the rats were measured.Biochemical tests were conducted to assess the four lipid profile parameters.Pathological examinations of the liver and colon were observed through hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining.16S rRNA sequencing technology was used for gene sequencing of the fecal microbiota in the rats,and non-targeted metabolomics was performed to detect fecal metabolites.[Results]Huanglian Zhimu Decoction can significantly reduce the fasting blood glucose(P<0.001)and serum levels of total cholesterol(TC),high-density lipoprotein(HDL)and low-density lipoprotein(LDL)in T2DM rats(P<0.05,P<0.01).It also alleviates hepatic steatosis and inflammatory cell infiltration in the liver tissue of T2DM rats induced by high-fat diet,and the synthesis of glycogen increased.Additionally,it repairs the intestinal barrier damage in the colonic tissue to a certain extent and reduce the infiltration of inflammatory cells.16S rRNA gene sequencing analysis revealed that Huanglian Zhimu Decoction can ameliorate intestinal microbiota disruption by reducing the ratio of Firmicutes to Bacteroidota(F/B)at the phylum level,down-regulating the abundance of harmful bacterial genera such as Allobaculum,Colidextribacter,Oscillibacter and Dorea,and up-regulating the abundance of beneficial bacterial genera including Prevotella_9 and Akkermansia muciniphila.Fecal metabolomics analysis indicated that Huanglian Zhimu Decoction improved abnormalities in primary bile acid metabolism and linoleic acid metabolism.[Conclusion]Huanglian Zhimu Decoction can reduce the fasting blood glucose and blood lipid levels in T2DM rats,and its mechanism of action may be related to regulating the structure of intestinal flora and influencing the metabolic pathways of primary bile acids and linoleic acid.These findings provide basis for further studying the mechanism of action of Huanglian Zhimu Decoction.
7.Research on brain damage and therapeutic effects of comorbid auditory and visual hallucinations and cognitive decline in patients with first-episode schizophrenia based on brain magnetic resonance imaging
Chunhai HUANG ; Wenzhen TU ; Ce CHEN ; Lei MENG ; Lixue QIU ; Jianjing ZHANG
Chinese Journal of Primary Medicine and Pharmacy 2025;32(9):1331-1336
Objective:To investigate brain damage and treatment efficacy in patients with first-episode schizophrenia with comorbid auditory and visual hallucinations and cognitive decline based on brain magnetic resonance imaging (MRI).Methods:This study adopted a retrospective cohort design. Eighty patients with first-episode schizophrenia who received treatment at Wenzhou Seventh People's Hospital from January to June 2024 were included in this study. The patients were divided into an observation group (40 cases of first-episode schizophrenia with comorbid auditory and visual hallucinations) and a control group (40 cases of first-episode schizophrenia without comorbid auditory and visual hallucinations) based on whether they had symptoms of comorbid auditory and visual hallucinations. Forty healthy individuals who concurrently underwent physical examinations were included in the normal group. All patients received standardized treatment. Cranial MRI data were collected from all subjects. Cranial MRI data, Positive and Negative Syndrome Scale (PANSS) score, Global Assessment of Functioning (GAF) score, and changes in cognitive function were compared among the three groups. Additionally, the changes in cranial MRI data, PANSS score, GAF score, and the score of MATRICS Consensus Cognitive Battery (MCCB) in the observation group were compared between before and after treatment.Results:The horizontal distance between the corpus callosum and the underside of the cingulate gyrus, the vertical distance between the corpus callosum and the underside of the cingulate gyrus, and PANSS and GAF scores in the observation group were all significantly higher than those in the normal and control groups (all P < 0.05). The scores on all MCCB scales in the observation group were significantly lower than those in the normal and control groups (all P < 0.05). After treatment, the left horizontal distance between the corpus callosum and the underside of the cingulate gyrus [(5.72 ± 0.71) mm] and the right horizontal distance [(5.13 ± 0.55) mm], as well as the left vertical distance [(6.37 ± 0.69) mm] and the right vertical distance [(5.61 ± 0.67) mm], were all significantly lower than the pre-treatment values [(6.98 ± 0.83) mm, (6.07 ± 0.49) mm, (7.54 ± 0.58) mm, and (6.52 ± 0.51) mm, t = 7.30, 8.07, 8.21, 6.84, all P < 0.05]. Post-treatment PANSS scores [(39.95 ± 6.65)] were significantly lower than pre-treatment scores [(97.47 ± 18.47)], while post-treatment GAF scores [(71.26 ± 8.87)] were significantly higher than pre-treatment scores [(34.68 ± 7.71), t = 18.53, 19.69, both P < 0.05]. Post-treatment scores for the MCCB [(8.57 ± 2.45), (2.25 ± 0.47), (25.16 ± 2.43), (24.10 ± 2.64), (17.08 ± 2.25), (20.43 ± 3.76), (2.07 ± 0.36), (22.16 ± 3.24), (57.81 ± 7.69), (0.28 ± 0.05)] were significantly higher than pre-treatment scores [(5.65 ± 1.37), (1.62 ± 0.34), (21.21 ± 2.27), (20.27 ± 1.78), (12.16 ± 2.08), (14.56 ± 2.34), (1.71 ± 0.25), (17.92 ± 1.64), (40.29 ± 6.56), (0.21 ± 0.03), t = 6.58, 6.87, 7.51, 7.61, 10.15, 8.38, 5.19, 7.38, 10.96, 7.59, all P < 0.05]. Conclusions:The comorbid auditory and visual hallucinations in patients with first-episode schizophrenia, based on brain MRI findings, are closely related to cognitive decline and brain damage. After treatment, both cognitive function and cranial damage in these patients have considerably improved, which is worthy of clinical consideration.
8.Preliminary investigation on the diagnostic values of sPD-1 and sPD-L1 changes in the acute rejection of rats after liver transplantation
Jiaowen YANG ; Tao CHEN ; Zhenglu WANG ; Lei CAO ; Jinpeng TU ; Hong ZHENG ; Wei GAO ; Zhongyang SHEN
Chinese Journal of Organ Transplantation 2025;46(3):226-231
Objective:To investigate the potential diagnostic value of peripheral blood soluble programmed cell death protein 1 (sPD-1) and soluble programmed cell death protein ligand 1 (sPD-L1) in acute rejection (AR) following liver transplantation using a rat model.Methods:A rat liver transplantation AR model was established, with the AR group (Lewis→BN) set as the experimental group (n=6) and the non-AR group (BN→BN) as the control group (n=6). Peripheral blood sPD-1 and sPD-L1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA) at 1 day before transplantation and at 1, 3, and 7 days postoperatively. On postoperative day 7, the expression levels of PD-1 and PD-L1 in liver tissues were detected by immunohistochemistry (IHC). Independent samples t-test and repeated measures ANOVA were used to compare the results between the two groups. Pearson correlation analysis was conducted to evaluate the relationship between sPD-1, sPD-L1, the sPD-1/sPD-L1 ratio, and the rejection activity index.Results:On postoperative day 7, the experimental group exhibited significantly higher peripheral sPD-1 levels (218.59±36.88 vs. 164.95±15.82 ng/L) and a higher sPD-1/sPD-L1 ratio (0.44±0.12 vs. 0.36±0.07), but lower sPD-L1 levels (379.56±73.41 vs. 423.64±96.55 ng/L) compared to the control group (all P<0.05). Correlation analysis revealed a significant positive correlation between sPD-1 levels and the rejection activity index ( r=0.680, P<0.05), as well as between the sPD-1/sPD-L1 ratio and the rejection activity index ( r=0.795, P<0.01), while no correlation was observed between sPD-L1 levels and the rejection activity index. IHC demonstrated positive PD-1 and PD-L1 expression in the liver tissues of the experimental group, whereas the control group showed negative expression. Conclusion:Peripheral blood sPD-1 levels and the sPD-1/sPD-L1 ratio are significantly associated with AR after liver transplantation in rats, suggesting their potential as biomarkers for diagnosing AR in liver transplant recipients.
9.Predictive Value of Residual Quantitative Flow Ratio for Long-term Vessel-oriented Composite Endpoints
Rui ZHANG ; Yanpu SHI ; Changdong GUAN ; Yanyan ZHAO ; Shengxian TU ; Bo YU ; Guosheng FU ; Yujie ZHOU ; Jian'an WANG ; Yundai CHEN ; Jun PU ; Kefei DOU ; Weixian YANG ; Yongjian WU ; Shubin QIAO ; Lei SONG
Chinese Circulation Journal 2025;40(9):862-869
Objectives:To explore the predictive value of residual Murray's law-based quantitative flow ratio(μQFR)on long-term vessel-oriented composite endpoints(VoCE).Methods:This retrospective study included 3 510 patients from the FAVOR Ⅲ China trial.Offline residual μQFR analysis was performed on all vessels(diameter≥2.5 mm)with 50%-90%stenotic lesions.Patients were stratified into high-,intermediate-,and low-risk groups based on residual μQFR tertiles.The primary endpoint was 3-year VoCE,defined as a composite of cardiac death related to the target vessel,target vessel-related spontaneous myocardial infarction,and ischemia-driven target vessel revascularization.Results:Offline analysis was performed on 5 256 vessels from 3 510 patients.The mean residual μQFR was 0.92±0.75.The high-risk group(residual μQFR≤0.91)with 1 554 patients(1 958 vessels);the intermediate-risk group(residual μQFR 0.92-0.96)with 1 211 patients(1 906 vessels);and the low-risk group(residual μQFR>0.96)with 745 patients(1 392 vessels).Over 3-year follow-up,VoCE occurred in 227 vessels(4.3%).The 3-year VoCE incidence was significantly higher in the high-risk group compared to the intermediate-and low-risk groups(6.2%vs.4.1%vs.2.5%,log-rank P<0.001),primarily driven by ischemia-driven target vessel revascularization(5.0%vs.3.0%vs.1.6%,log-rank P<0.001).Hypertension(OR=0.83,95%CI:0.72-0.96),hypercholesterolemia(OR=0.84,95%CI:0.73-0.97),bifurcation lesions(OR=0.72,95%CI:0.63-0.83),moderate/severe calcification(OR=0.70,95%CI:0.57-0.84),and tandem lesions(OR=0.59,95%CI:0.47-0.75)were independent predictors of lower residual μQFR values.Conclusions:Lower residual μQFR is significantly associated with increased VoCE risk during the 3-year follow up period.
10.Diagnostic value of multi-slice spiral CT in pulmonary nodules of different properties
Xun WANG ; Lei TU ; Si-jia ZHOU
Journal of Regional Anatomy and Operative Surgery 2025;34(9):809-812
Objective To explore the diagnostic value of multi-slice spiral CT in pulmonary nodules of different properties.Methods The clinical data of 150 patients with pulmonary nodules who were treated at Tongren People's Hospital from October 2022 to October 2023 were collected for a retrospective study.All patients underwent multi-slice spiral CT examinations,and the benign and malignant grouping was conducted based on the results of lung biopsy.The CT imaging characteristics and CT perfusion parameters of patients with benign pulmonary nodulesand malignant pulmonary nodules were compared,and the diagnostic value of multi-slice spiral CT for benign and malignant pulmonary nodules was evaluated.Results The results of lung biopsy showed that among the 150 patients with pulmonary nodules,there were 62 patients with malignant pulmonary nodules(malignant nodule group)and 88 patients with benign pulmonary nodules(benign nodule group).The proportion of calcification patients in the malignant nodule group was significantly lower than that in the benign nodule group,while the proportions of patients with vacuolar sign,lobulation sign,spinous protrusion,and spiculation sign were significantly higher than those in the benign nodule group,and the differences were statistically significant(P<0.05).There was no statistically significant difference in the mean transit time(MTT)between the malignant nodule group and the benign nodule group(P>0.05).The blood flow(BF),blood volume(BV),and permeability surface(PS)of patients in the malignant nodule group were significantly higher than those in the benign nodule group,and the differences were statistically significant(P<0.05).Taking the lung biopsy results of patients with pulmonary nodules as the gold standard,the diagnostic accuracy of multi-slice spiral CT for malignant nodules was 94.00%,the diagnostic sensitivity was 95.16%,the diagnostic specificity was 93.18%,the positive predictive value was 90.77%,and the negative predictive value was 96.47%.Conclusion There are significant differences in CT imaging features and perfusion parameters among patients with pulmonary nodules of different properties.Multi-slice spiral CT can effectively distinguish benign and malignant pulmonary nodules and has good diagnostic efficiency.

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