1.Yishen Tongluo Prescription Ameliorates Oxidative Stress Injury in Mouse Model of Diabetic Kidney Disease via Nrf2/HO-1/NQO1 Signaling Pathway
Yifei ZHANG ; Xuehui BAI ; Zijing CAO ; Zeyu ZHANG ; Jingyi TANG ; Junyu XI ; Shujiao ZHANG ; Shuaixing ZHANG ; Yiran XIE ; Yuqi WU ; Zhongjie LIU ; Weijing LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):41-51
ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease (DKD) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) signaling pathway. MethodsSpecific pathogen-free (SPF) male C57BL/6 mice were assigned into a control group (n=10) and a modeling group (n=50). The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group, a semaglutide (40 μg·kg-1) group, and high-, medium-, and low-dose (18.2, 9.1, 4.55 g·kg-1, respectively) Yishen Tongluo prescription groups, with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured, and the kidney index (KI) was calculated. Serum levels of creatinine (SCr), blood urea nitrogen (BUN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin, periodic acid-Schiff, periodic acid-silver methenamine, and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty acid-binding protein (L-FABP), nitric oxide synthase (NOS), glutathione (GSH), total antioxidant capacity (T-AOC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 (Keap1) and malondialdehyde (MDA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group, the DKD model group showed rises in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with glomerular hypertrophy, renal tubular dilation, thickened basement membrane, mesangial expansion, and collagen deposition. Additionally, the model group showed elevated levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, lowered levels of GSH and T-AOC, up-regulated expression of MDA and Keap1, and down-regulated expression of Nrf2, HO-1, NQO1, and glutamate-cysteine ligase catalytic subunit (GCLC) (P<0.05). Compared with the model group, the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with alleviated pathological injuries in the renal tissue. In addition, the three groups showed lowered levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, elevated levels of GSH and T-AOC, down-regulated expression of MDA and Keap1, and up-regulated expression of Nrf2, HO-1, NQO1, and GCLC (P<0.05). ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway, mitigating oxidative stress, and reducing renal tubular injuries.
2.Dipsacus asper Treats Alzheimer's Disease in Caenorhabditis elegans by Regulating PPARα/TFEB Pathway
Mengmeng WANG ; Jianping ZHAO ; Limin WU ; Shuang CHU ; Yanli HUANG ; Zhenghao CUI ; Yiran SUN ; Pan WANG ; Hui WANG ; Zhenqiang ZHANG ; Zhishen XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):104-114
ObjectiveTo investigate the anti-Alzheimer's disease (AD) effect of Dipsacus asper(DA) in the Caenorhabditis elegans model, and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α (PPARα)/transcription factor EB (TFEB) pathway. MethodsFirst, transgenic AD C. elegans individuals were assigned into the blank control, model, positive control (WY14643, 20 µmol·L-1), and low-, medium-, and high-dose (100, 200, and 400 mg·L-1, respectively) DA groups. The amyloid β-42 (Aβ42) formation in the muscle cells, the paralysis time, and the deposition of amyloid β-protein (Aβ) in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ, LC3I, LAMP2, and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction (Real-time PCR) was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα, and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain (LBD). ResultsCompared with the model group, the positive control group and 200 and 400 mg·L-1 DA groups showed prolonged paralysis time (P<0.05), and all the treatment groups showed decreased Aβ deposition in the head (P<0.01). DA within the concentration range of 50-500 mg·L-1 did not affect the viability of BV2 cells. In addition, DA enhanced the autophagy flux (P<0.05), up-regulated the mRNA levels of beclin1, Atg5, LAMP2, and CLN2 (P<0.05, P<0.01), promoted the nuclear translocation of TFEB (P<0.05), increased LAMP2 expression and autophagy flux (P<0.05, P<0.01), and enhanced the transcriptional activities of PPARα and TFEB (P<0.01). The positive control group and 200 and 400 mg·L-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus (P<0.01). UPLC-MS detected nine known compounds of DA, from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.
3.Mechanism of Yishen Tongluo Formula regulating the TLR4/MyD88/NF-κB signaling pathway to ameliorate pyroptosis in diabetic nephropathy mice
Yifei ZHANG ; Zijing CAO ; Zeyu ZHANG ; Xuehui BAI ; Jingyi TANG ; Junyu XI ; Jiayi WANG ; Yiran XIE ; Yuqi WU ; Xi GUO ; Zhongjie LIU ; Weijing LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):21-33
Objective:
To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway.
Methods:
Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue.
Results:
Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated.
Conclusion
Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.
4.Value of ultra-high-resolution photon-counting detector CT in improving neurovascular image quality
Guang YAO ; Jun LI ; Junli REN ; Xing LIU ; Lichen REN ; Yiran WANG ; Xiaolei ZHANG ; Jiawei LIU ; Jianbo GAO ; Yonggao ZHANG
Chinese Journal of Radiology 2025;59(12):1353-1360
Methods:This study was a cross-sectional study. A prospective cohort study enrolled 42 patients with clinically suspected acute cerebrovascular disease and those undergoing follow-up examinations after intracranial vascular stenting at the First Affiliated Hospital of Zhengzhou University from June 2024 to May 2025. All patients underwent UHR PCD-CT examinations of the head and neck. Reconstructions were performed based on raw data, yielding conventional standard resolution (SR group) reconstructions and UHR images reconstructed using four distinct convolution kernels (Hv40, Hv48, Hv56, Hv64) in separate groups (Hv40 UHR group, Hv48 UHR group, Hv56 UHR group, Hv64 UHR group). Regions of interest were selected in the anterior cerebral artery, middle cerebral artery, posterior cerebral artery, posterior communicating artery, and anterior communicating artery. CT values and standard deviation (SD) values were measured for each artery, and signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Additionally, the sharpness of the vessel edges and the full-width-half-maximum (FWHM) of each artery were measured. One-way analysis of variance or the nonparametric Kruskal-Wallis test was used to compare the subjective and objective image quality metrics across the five groups. Pairwise comparisons were performed using the LSD test or Dunn method.Results:Statistically significant differences were observed in the overall comparison of vascular imaging SD, SNR, CNR, vascular edge sharpness, and FWHM among the SR group, Hv40 UHR group, Hv48 UHR group, Hv56 UHR group, and Hv64 UHR group ( P<0.05). No statistically significant differences in CT values were found ( P>0.05). Pairwise comparisons revealed statistically significant differences between all groups ( P<0.05), except that no significant differences were observed in image SD, SNR, CNR, vascular edge sharpness, or FWHM between the Hv56 UHR and Hv64 UHR groups ( P>0.05). Conclusions:UHR PCD-CT provides better image quality for neurovascular imaging. For the display of small intracranial vessels, the Hv64 provides sharper vessel walls and better subjective image quality compared to the less sharp convolutional cores.Objective:To explore the value of ultra-high resolution (UHR) photon-counting detector CT (PCD-CT) to improve the quality of neurovascular images.
5.Feasibility and efficacy of TPLA with single-fiber for prostate in treating BPO
Yiran JIANG ; Xiao HAN ; Peipei YANG ; Jing XIAO ; Ran LI ; Xin TONG ; Dongxing ZHANG ; Xiaohui ZHAO ; Xiangdong HU ; Xianquan SHI
China Medical Equipment 2025;22(11):92-96
Objective:To assess the feasibility and efficacy of transperineal laser ablation(TPLA)with single laser fiber in treating benign prostatic obstruction(BPO).Methods:From April 2021 to March 2024,a total of 13 BPO patients were selected from Beijing Friendship Hospital.TPLA was performed using a single laser fiber,which was guided by transrectal biplane ultrasound.The single laser fiber was used to undergo TPLA under the guidance of trans-rectal dual-plane ultrasound.The intraoperative time,ablation time,energy consumption,indwelling time of catheter,and complications were observed.The postoperative 6 months was chosen as the cut-off point of follow-up,and the pre and postoperative changes of international prostate symptom score(IPSS),quality of life index(QoL),prostate volume(PV),residual urine volume(RUV)and the maximum urine flow rate(Qmax)were compared.Results:All 13 patients successfully underwent TPLA with single laser fiber.The average operation time was(55.1±18.3)min,and the average ablation time was(16.3±1.7)min,and average energy consumption was(3951.6±459.7)J,and the median value of indwelling time of catheter was 7(7,10)days.The number of postoperative complication was 2 cases,and both them belonged to Clavien-Dindo grade II complication.At the postoperative 6th month,the IPSS,QoL,PV,Qmax and RUV of all patients were improved,all of which were better than preoperative these indicators,and the differences were significant(t=12.102,-3.228,-3.181,-2.581,-2.936,P<0.05).Conclusion:The application of single laser fiber in conducting TPLA operation is feasibility at technical aspect,and it can achieve the therapeutic goals of improving patients'symptoms and enhancing their quality of life.Although its operational time is slightly longer than that of using multiple fibers simultaneously,it can effectively reduce the cost of expenditure for consumables.
6.Brain functional networks in children with spastic cerebral palsy and their correlation with motor function as analyzed based on fNIRS
Yangyang CAO ; Xiaokang TANG ; Qianyu GUO ; Jun WANG ; Dengna ZHU ; Gongxun CHEN ; Yuhang ZHANG ; Junying YUAN ; Juan SONG ; Yiran XU
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(11):998-1004
Objective:To explore the characteristics of the brain functional networks in children with spastic cerebral palsy (SCP) while at rest and to correlate them with motor functioning.Methods:Thirty-six children with SCP were enrolled as the SCP group, while thirty-four age-matched healthy children were recruited as the control group (the HC group). Functional near-infrared spectroscopy was used to detect changes in the concentration of oxygenated hemoglobin in the children′s cerebral cortex while at rest. The left prefrontal cortex (LPFC), right prefrontal cortex (RPFC), left motor cortex (LMC), and right motor cortex (RMC) were selected as regions of interest. Phase locking values (PLVs) were used to evaluate the strength of functional connectivity (FC) among these brain regions, and graph theory methods were applied to analyze the topological properties of the brain networks. Motor functioning was assessed using the gross motor function measure (GMFM).Results:The analyses of FC strength revealed that the SCP group had significantly weaker FC among all of the regions of interest while at rest compared to the HC group. Their PLVs for LPFC-RPFC, LPFC-RMC, RPFC-RMC and LMC-RMC connectivity were all significantly smaller. Graph theory analysis showed that the SCP group had significantly lower global efficiency (GE) and smaller clustering coefficients (CCs) and network density (D), while their characteristic path lengths were significantly longer. According to the correlation analysis, the PLVs for LMC-RMC connections in the SCP group were positively correlated with their scores on dimensions D and E of the GMFM ( r=0.496 and r=0.579 respectively). GE ( r=0.587 and r=0.642) and CC ( r=0.318 and r=0.759) showed similar significant positive correlations with GMFM dimensions D and E. Conclusions:At rest, the functional networks in the brains of children with SCP exhibit abnormalities closely associated with their motor dysfunction.
7.Clinical characteristics and steroid hormone LC-MS/MS analysis in four male patients with 17α-hydroxylase/17, 20-lyase deficiency
Wei ZHANG ; Yuying YANG ; Sichang ZHENG ; Yuwen ZHANG ; Wencui WANG ; Rulai HAN ; Yiran JIANG ; Yizhi HE ; Lei YE ; Shouyue SUN
Chinese Journal of Endocrinology and Metabolism 2025;41(10):837-843
Objective:To analyze the clinical characteristics and gene mutations of 4 patients with the male phenotype of 17α-hydroxylase /17, 20-lyase deficiency(17-OHD), in order to improve the recognition and appropriate management of atypical cases.Methods:A retrospective analysis was performed on the clinical features, biochemical findings, and gene mutations of 4 patients with the male phenotype of 17-OHD treated in our hospital between 2018 and 2023.Results:The social gender of all 4 patients with 17-OHD was male. None of the 4 patients had hypertension or hypokalemia, but all had micropenis and gynecomastia. Two patients had adrenal hyperplasia, while adrenal morphology was normal in the other two. One patient had decreased bone mass. There were typical changes in the steroid synthesis-related hormone spectrum: progesterone was significantly elevated in all 4 patients, 17-hydroxyprogesterone was not markedly abnormal, cortisol, dehydroepiandrosterone sulfate(DHEAS) and estradiol levels were low, and testosterone levels were also low.Conclusion:17-OHD is a rare type of congenital adrenal hyperplasia, with the male phenotype being even rarer. Early symptoms are often atypical, resulting in high rates of misdiagnosis and missed diagnosis. Patients without hypertension and hypokalemia are particularly prone to diagnostic confusion. Male patients with unexplained progesterone elevation, poor secondary sexual development, and gynecomastia should undergo timely steroid hormone profiling and genetic testing to avoid misdiagnosis and missed diagnosis.
8.Research progress of suture augmentation in anterior cruciate ligament reconstruction.
Jiaxin LIU ; Hongyu LI ; Meng WANG ; Yiran WANG ; Guanxin GUO ; Hangzhou ZHANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(4):504-510
OBJECTIVE:
To summarize the research progress of suture augmentation (SA) in anterior cruciate ligament (ACL) reconstruction.
METHODS:
A comprehensive review of recent literature about SA in ACL reconstruction at home and abroad was conducted. The efficacy of SA in ACL reconstruction was evaluated by examining the definition, biomechanics, and histological studies of SA, along with its clinical application status in ACL reconstruction.
RESULTS:
SA demonstrates significant advantages in enhancing the biomechanical stability of ACL grafts, reducing the risk of re-rupture, and accelerating postoperative recovery. Specifically, SA improves graft stiffness, ultimate failure strength, and cyclic stability, thereby diminishing the risk of early postoperative failure and joint instability. Histologically, it fosters remodeling and tendon-bone integration through early load-sharing mechanisms; however, stress shielding may interfere with natural remodeling processes, warranting further attention. Clinically, SA reduces graft failure rates and the need for revision surgeries, markedly improving knee joint stability and functional recovery in young patients. Nevertheless, its impact on graft maturation and potential complications remains controversial.
CONCLUSION
Despite the many advantages of SA in ACL reconstruction, future endeavors should focus on optimizing tensioning techniques, developing bioactive materials, and conducting large-scale randomized controlled trials to further elucidate its clinical value and scope of applicability, providing a more reliable solution for ACL reconstruction.
Humans
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Anterior Cruciate Ligament Reconstruction/methods*
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Biomechanical Phenomena
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Anterior Cruciate Ligament/surgery*
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Anterior Cruciate Ligament Injuries/surgery*
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Suture Techniques
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Sutures
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Tendons/transplantation*
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Joint Instability/prevention & control*
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Knee Joint/surgery*
9.Determination and evaluation of serum monosaccharides in patients with early-stage lung adenocarcinoma.
Wenhao SU ; Cui HAO ; Yifei YANG ; Pengjiao ZENG ; Huaiqian DOU ; Meng ZHANG ; Yanli HE ; Yiran ZHANG ; Ming SHAN ; Wenxing DU ; Wenjie JIAO ; Lijuan ZHANG
Chinese Medical Journal 2025;138(3):352-354
10.Source analysis of epileptiform discharges in idiopathic epilepsy with centrotemporal spikes: A study based on magnetoencephalography
Yiran DUAN ; Yongbo ZHANG ; Yuping WANG
Journal of Apoplexy and Nervous Diseases 2025;42(8):722-726
Objective Idiopathic rolandic epilepsy syndrome (IRES) is the most common epilepsy syndrome in childhood, and its lesion site remains undetermined. This article aims to investigate the source of epileptiform discharges in IRES using magnetoencephalography (MEG).Methods A total of 70 patients with IRES were enrolled in this prospective MEG-based study, among whom there were 53 children with benign epilepsy of childhood with centrotemporal spikes (BECTS), 12 children with atypical benign partial epilepsy (ABPE), 3 children with Landau-Kleffner syndrome (LKS), and 2 children with epileptic encephalopathy with continuous spike-and-waves during slow-wave sleep (CSWS). Epileptiform discharges were collected independently from each patient 10 times, and an MEG source analysis was performed. Standardized low-resolution brain electromagnetic tomography was used to perform source localization of the distributed source model. The spike source density was quantified into amplitude, and source location was determined according to the Desikan-Killiany atlas. The association between the distribution of spike source in brain and clinical manifestations was analyzed.Results In IRES, there were significant differences in the source locations of epilepsy discharge between BECTS, ABPE, LKS, and CSWS. The current source density of CSWS was stronger in the frontal lobe, the temporal lobe, and the anterior cingulate gyrus, while that of ABPE was stronger in the frontal lobe, and that of BECTS and LKS were stronger in the temporal lobe. The more severe phenotype of epilepsy, such as generalized tonic-clonic seizure, was associated with a stronger current source density in the brain, which was consistent with electroencephalography manifestations.Conclusion This study identifies different sources of epileptiform discharges in IRES. The density distribution of these spike sources may help to explain the discharge, cognitive, and neuropsychological characteristics in different subtypes of IRES.
Magnetoencephalography


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