1.Effect of Modified Duhuo Jisheng Mixture Regulating PI3K/Akt/mTOR Signaling Pathway on Synoviocyte Pyroptosis in Rabbit Models of Knee Osteoarthritis
Zifeng YE ; Yiwei YUAN ; Liguo QIU ; Xuyi TAN ; Liang OU ; Gaoyan KUANG ; Min LU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):170-179
ObjectiveTo explore the potential mechanisms of action of the modified Duhuo Jisheng Mixture (JDJM) in treating synovial lesions in knee osteoarthritis (KOA). MethodsA total of 43 male New Zealand white rabbits were randomly allocated into a blank group (n=8) and a model group (n=35). The KOA model was induced by immobilizing the right hind limb with a high-molecular resin plaster bandage, with a modeling period of 6 weeks, resulting in successful modeling in 32 rabbits. These rabbits were then randomly allocated to the model group, celecoxib group, JDJM group and JDJM+740Y-P group, each consisting of 8 rabbits. The celecoxib group received celecoxib via gavage at a single dose of 0.009 3 g·kg-1, while the JDJM was administered a single dose of 6.8 mL·kg-1 (4.515 2 g·kg-1) of the herbal preparation via gavage. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway activator + JDJM group received 4.515 2 g·kg-1 of the herbal preparation via gavage along with an auricular vein injection of 0.15 μmol·kg-1 740Y-P. For a period of 6 weeks, the remaining groups received an equal volume of physiological saline via gavage daily. After the medication period, the knee joint pain threshold and circumference were measured, and hematoxylin-eosin (HE) staining was performed to assess the pathological changes in the synovial tissues. Enzyme-linked immunosorbent assay (ELISA) measured the levels of interleukin-1β (IL-1β), interleukin-6 (IL-18) and tumor necrosis factor-α (TNF-α) in the joint fluid. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to assess the mRNA expression of PI3K, Akt, mTOR, NOD-like receptor protein 3 (NLRP3), cysteine-requiring aspartate protease-1 (Caspase-1) and gasdermin D (GSDMD) in the synovial tissues. Immunohistochemical (IHC) assay was performed to assess the protein expression of NLRP3, Caspase-1 and GSDMD. Western blot was carried out to analyze the protein expression of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, NLRP3, Caspase-1 and GSDMD. ResultsCompared to the blank group, the model group showed a significant increase in knee joint circumference and decrease in pain threshold, the synovial tissue pathology score was higher (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid significantly increased (P<0.01). PI3K, Akt, mTOR phosphorylation as well as mRNA and protein expression increased (P<0.01), while the mRNA and protein expression levels of NLRP3, Caspase-1 and GSDMD also significantly increased (P<0.01). Compared to the model group, the celecoxib and JDJM groups exhibited a significant reduction in knee joint circumference and increase in pain threshold, the synovial tissue pathology score was lower (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid decreased (P<0.01). The mRNA and protein expression of p-PI3K, p-Akt, p-mTOR, NLRP3, Caspase-1 and GSDMD were reduced (P<0.01). Compared to the JDJM group, the JDJM+740Y-P group showed a decrease in the improvement of synovial lesions, an increase in knee joint circumference, and a decrease in pain threshold. The synovial tissue pathology score was lower (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid were higher (P<0.01). The mRNA and protein expression of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, NLRP3, Caspase-1 and GSDMD increased (P<0.01). ConclusionJDJM is effective in treating KOA. Its mechanism may involve modulating the PI3K/Akt/mTOR pathway in synovial tissues, inhibiting pyroptosis, reducing inflammatory factor release, and protecting bony structures.
2.Clinical Validation of a Rapid Automated Lymphoma Next-Generation Sequencing Panel
Michael KRIGSTEIN ; Emily JUDE ; Aleisha JAFFREY ; Stephen BYE ; Bin WANG ; Min Ru QIU ; David MA
Annals of Laboratory Medicine 2026;46(3):319-326
Background:
Our genomic understanding of lymphomas, a heterogeneous group of neoplasms, has grown exponentially. The latest World Health Organization (WHO) and International Consensus classifications reflect the importance of genetic assessment in the diagnosis and prognostication of and therapeutic decision making in lymphoid neoplasms. To address this clinical need for routinely available and timely testing, we aimed to validate the Ion AmpliSeq Liverpool Lymphoid Network Panel (IALLNP; Thermo Fisher Scientific, Waltham, MA, USA).
Methods:
We clinically validated the IALLNP on the Ion Torrent Genexus Sequencer (Thermo Fisher Scientific). The panel detects single-nucleotide variants (SNVs) and insertions/deletions (indels) in 60 clinically relevant genes. The validation set included a commercial control and 54 DNA samples covering the spectrum of clinically aggressive and indolent lymphomas.
Results:
After optimizing for poor coverage regions, recurrent artifacts, and false-negative calls, the panel showed good performance in terms of depth of coverage, on-target reads, and uniformity. Its sensitivity for SNVs and indels at a lower limit of detection of 5% variant allele frequency (VAF) was 100%. Specificity in variant-negative samples was 100%, and the mean per-sample number of false-positive variants—which were easily identifiable and excluded upon interrogation of raw data—was 0.4. The panel demonstrated 92.8% reproducibility; however, all nonreproducible variants fell below the 5% VAF analytical threshold.
Conclusions
The IALLNP is an accurate and reproducible next-generation sequencing panel that delivers genetic results for lymphoid neoplasms in a clinically meaningful timeframe.
3.Influencing factors and prognosis of postoperative complications in elderly(≥75 years)patients with renal cell carcinoma after laparoscopic surgery
Zhiying WU ; Min QIU ; Dameng PAN ; Xiaojun TIAN ; Lei ZHAO ; Hongxian ZHANG ; Shudong ZHANG ; Lulin MA
Journal of Modern Urology 2026;31(6):503-509
Objective To analyze the postoperative complications and survival outcomes of elderly patients with renal cell carcinoma undergoing laparoscopic surgery, and to identify the influencing factors, so as to provide reference for improving the safety of laparoscopic surgery in such patients. Methods A retrospective analysis was conducted on the clinical, surgical, and pathological data of 153 patients aged ≥75 years who underwent laparoscopic nephrectomy for renal cell carcinoma at our hospital during 2012 and 2025.Logistic regression analyses were performed to identify factors influencing postoperative complications, and a nomogram was constructed and validated to predict the complications.Kaplan-Meier method was used to draw the survival curve, and the effects of different surgical approaches on the prognosis and the survival difference in the age subgroups (75-<80 years, ≥80 years) were analyzed.Cox regression analyses were conducted to determine factors affecting survival outcomes. Results Among the 153 patients, 15 developed postoperative complications, including 5 severe cases. Multivariate logistic regression identified Charlson Comorbidity Index (CCI) ≥3 and prolonged operation time as independent risk factors for postoperative complications (P<0.05).The C-index of the logistic regression model constructed based on these factors (age, CCI≥3 and operation time) was 0.77 (95%CI:0.64-0.90), with an average absolute error of 1.6%.Subgroup analysis revealed superior overall survival in patients aged 75-<80 years undergoing partial nephrectomy compared to radical nephrectomy (P=0.005 6).No statistically significant difference in overall survival was observed among patients ≥80 years who received different surgical approaches (P=0.062).Multivariate Cox regression analysis identified preoperative low albumin levels, preoperative renal insufficiency, tumor diameter>4 cm, and pathological stage as independent risk factors for overall survival (P<0.05). Conclusion Laparoscopic surgery is safe and effective for elderly patients with renal cell carcinoma, with survival outcomes correlated to nutritional status, renal function, tumor size and pathological staging.Patients aged ≥80 years still derive surgical benefit, and no survival differences exist between different surgical approaches in this age group.
4.Mechanism of Ruyan Neixiao Cream in Promoting Ferroptosis in Breast Precancerous Lesion Cells by Regulating Nrf2/SLC7A11/GPX4 Signaling Pathway
Haotian ZHANG ; Yebei QIU ; Ran SU ; Xianxin YAN ; Min MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):98-107
ObjectiveTo explore the mechanism by which Ruyan Neixiao cream (RUC) induces ferroptosis in breast precancerous lesion (BPL) cells, and to enrich the theoretical foundation for its use in the treatment of BPL. MethodsThe inhibition of cell proliferation by 1%, 2%, and 4% concentrations of Ruyanneixiao Cream transdermal solution (RUT) was assessed using cell counting kit-8 (CCK-8) and a colony formation assay. Reactive oxygen species (ROS) were measured using the DCFH-DA probe, and the levels of ferrous ions (Fe2+), glutathione (GSH), and malondialdehyde (MDA) were determined using appropriate kits. Lipid peroxidation was detected with the C11-BODIPY581/591 fluorescent probe. The expression of nuclear factor E2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) proteins was analyzed by Western blot. The BPL rat model was constructed using 2,2′-bis(hydroxymethyl)butyric acid (DMBA) combined with estrogen and progesterone, and the rats were treated with RUC for external application. After the 12th cycle, the rats were euthanized, and histopathological changes in breast tissue were observed by hematoxylin-eosin (HE) staining. Fe2+ and MDA levels in breast tissue were measured using corresponding kits. The expression of Nrf2, SLC7A11, and GPX4 proteins in BPL rat breast tissue was detected by immunohistochemistry (IHC) and Western blot. ResultsCompared with the matrix group, the cell viability of MCF-10AT cells in the 1%, 2%, and 4% RUT groups was significantly reduced (P<0.05) in a concentration-dependent manner, with the 24-hour half inhibitory concentration (IC50) being 2.23%. Compared with the 4% RUT group, cell viability in the RUT + Fer-1 group was significantly increased (P<0.05). Compared with the matrix group, the colony formation rates of MCF-10AT cells in the 1%, 2%, and 4% RUT groups were significantly decreased (P<0.05). Compared with the 4% RUT group, the cell colony formation rate of the RUT + Fer-1 group was significantly increased (P<0.05). Compared with the matrix group, the levels of ROS and Fe2+ in the 1%, 2%, and 4% RUT groups were significantly increased (P<0.05), while GSH levels were significantly decreased (P<0.05), and MDA and lipid peroxidation levels were significantly increased (P<0.05). Compared with the 4% RUT group, ROS and Fe2+ levels in the RUT + Fer-1 group were significantly reduced (P<0.05), while GSH levels were significantly increased (P<0.05), and MDA and lipid peroxidation levels were significantly reduced (P<0.05). Compared with the matrix group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the 1%, 2%, and 4% RUT groups were significantly decreased (P<0.05). Compared with the 4% RUT group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the RUT + Fer-1 group were significantly increased (P<0.05). In the in vivo experiment, compared with the matrix group, the breast tissue histopathological status of the BPL rats in the RUC group was effectively improved, with less dilatation of the mammary ducts and more orderly duct arrangement. No pathological morphology indicative of invasive cancer was observed. Compared with the matrix group, Fe2+ and MDA levels in the mammary tissue of the RUC group were significantly increased (P<0.05). Compared with the matrix group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the mammary tissue of the RUC group were significantly reduced (P<0.05). ConclusionRUC may induce ferroptosis in BPL cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway, increasing Fe2+ accumulation, and promoting lipid peroxidation.
5.Mechanism of Ruyan Neixiao Cream in Promoting Ferroptosis in Breast Precancerous Lesion Cells by Regulating Nrf2/SLC7A11/GPX4 Signaling Pathway
Haotian ZHANG ; Yebei QIU ; Ran SU ; Xianxin YAN ; Min MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):98-107
ObjectiveTo explore the mechanism by which Ruyan Neixiao cream (RUC) induces ferroptosis in breast precancerous lesion (BPL) cells, and to enrich the theoretical foundation for its use in the treatment of BPL. MethodsThe inhibition of cell proliferation by 1%, 2%, and 4% concentrations of Ruyanneixiao Cream transdermal solution (RUT) was assessed using cell counting kit-8 (CCK-8) and a colony formation assay. Reactive oxygen species (ROS) were measured using the DCFH-DA probe, and the levels of ferrous ions (Fe2+), glutathione (GSH), and malondialdehyde (MDA) were determined using appropriate kits. Lipid peroxidation was detected with the C11-BODIPY581/591 fluorescent probe. The expression of nuclear factor E2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) proteins was analyzed by Western blot. The BPL rat model was constructed using 2,2′-bis(hydroxymethyl)butyric acid (DMBA) combined with estrogen and progesterone, and the rats were treated with RUC for external application. After the 12th cycle, the rats were euthanized, and histopathological changes in breast tissue were observed by hematoxylin-eosin (HE) staining. Fe2+ and MDA levels in breast tissue were measured using corresponding kits. The expression of Nrf2, SLC7A11, and GPX4 proteins in BPL rat breast tissue was detected by immunohistochemistry (IHC) and Western blot. ResultsCompared with the matrix group, the cell viability of MCF-10AT cells in the 1%, 2%, and 4% RUT groups was significantly reduced (P<0.05) in a concentration-dependent manner, with the 24-hour half inhibitory concentration (IC50) being 2.23%. Compared with the 4% RUT group, cell viability in the RUT + Fer-1 group was significantly increased (P<0.05). Compared with the matrix group, the colony formation rates of MCF-10AT cells in the 1%, 2%, and 4% RUT groups were significantly decreased (P<0.05). Compared with the 4% RUT group, the cell colony formation rate of the RUT + Fer-1 group was significantly increased (P<0.05). Compared with the matrix group, the levels of ROS and Fe2+ in the 1%, 2%, and 4% RUT groups were significantly increased (P<0.05), while GSH levels were significantly decreased (P<0.05), and MDA and lipid peroxidation levels were significantly increased (P<0.05). Compared with the 4% RUT group, ROS and Fe2+ levels in the RUT + Fer-1 group were significantly reduced (P<0.05), while GSH levels were significantly increased (P<0.05), and MDA and lipid peroxidation levels were significantly reduced (P<0.05). Compared with the matrix group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the 1%, 2%, and 4% RUT groups were significantly decreased (P<0.05). Compared with the 4% RUT group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the RUT + Fer-1 group were significantly increased (P<0.05). In the in vivo experiment, compared with the matrix group, the breast tissue histopathological status of the BPL rats in the RUC group was effectively improved, with less dilatation of the mammary ducts and more orderly duct arrangement. No pathological morphology indicative of invasive cancer was observed. Compared with the matrix group, Fe2+ and MDA levels in the mammary tissue of the RUC group were significantly increased (P<0.05). Compared with the matrix group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the mammary tissue of the RUC group were significantly reduced (P<0.05). ConclusionRUC may induce ferroptosis in BPL cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway, increasing Fe2+ accumulation, and promoting lipid peroxidation.
6.A Brief Exploration of Endogenous Wind (内风) by Tracing Its Origin and Development
Xiaojin QIU ; Min LI ; Fei YU ; Ruiying SHU ; Dandan DING
Journal of Traditional Chinese Medicine 2025;66(2):197-200
The historical development of endogenous wind (内风) is traced with time as the thread, based on the progression of factors such as syndromes, causes of disease, and pathogenesis. It is believed that the concept of wind syndrome originated in The Inner Canon of Yellow Emperor (《黄帝内经》), encompassing both exogenous wind (外风) and endogenous wind syndrome. Over time, exogenous wind syndrome gradually evolved into mild syndromes and severe syndromes, while endogenous wind syndrome emerged from severe syndromes of exogenous wind. Endogenous wind syndrome has both syndrome and pathogenic attributes, and its theoretical system has gradually become more refined. Based on the theories of ancient and modern medical practitioners, and combining the holistic perspectives with Xiang (象) thinking, it is proposed that endogenous wind has both physiological and pathological distinctions. The physiological endogenous wind refers to the liver's moderate dispersing and regulating function, which helps to distribute qi (气), blood, and body fluids, while pathological endogenous wind arises from abnormal liver dispersal. Therefore, in clinical practice, different treatment methods, such as tonifying, unblocking, and warming, can be applied according to the differentiation of deficiency and excess in the pathogenesis.
7.Tension hydrocele: report of 2 cases and literature review
Xun ZHAO ; Shumin WANG ; Min QIU ; Chuxiao XU ; Guoliang WANG ; Shudong ZHANG
Journal of Modern Urology 2025;30(1):69-72
[Objective] To explore the diagnosis and treatment experience of tension hydrocele. [Methods] The clinical data of 2 patients with tension hydrocele treated in our hospital were retrospectively analyzed.Relevant literature was retrieved to analyze the clinical characteristics of this disease. [Results] Case 1 was diagnosed due to swelling and pain of the left scrotum after trauma for more than one month, which worsened for one day.Physical examination showed high tension in the left scrotum and positive light transmission test.Ultrasound examination revealed that the blood flow signal in the left testis disappeared.Emergency left scrotal exploration and hydrocelectomy were performed.There was no sign of testis torsion during the operation.Case 2 was diagnosed mainly due to hydrocele of the right testis for 1 year, which worsened for 1 week and complicated with testis distension and pain.Physical examination showed high tension in the right scrotum and positive light transmission test.Ultrasound examination revealed that the blood flow signal in the right testis decreased.After 40ml of fluid was extracted under ultrasound monitoring, the blood flow signal in the right testis recovered.Hydrocelectomy was performed the next day.During the follow-up of 8 months, there was no recurrence of hydrocele.A search of domestic and foreign literature showed that there were no reports in domestic literature, while a total of 11 cases were reported in foreign literature. [Conclusion] Tension hydrocele of the testis is a rare emergency of the scrotum.Surgery or decompression should be performed as soon as possible to restore testicular blood supply, and hydrocelectomy should be performed simultaneously or in stages to prevent recurrence.
8.Experimental study of magnetic tracer technique in the localization of pulmonary nodules in dogs
Huan-chen SHA ; Miao-miao ZHANG ; Jia-hui WAN ; Qiu-ye ZHONG ; Rui-min GONG ; Yi LYU ; Xiao-peng YAN
Journal of Regional Anatomy and Operative Surgery 2025;34(10):841-845
Objective To investigate the feasibility of magnetic tracer technique for locating pulmonary nodules.Methods A tracer magnet and a matching puncture instrument were designed by ourselves for locating pulmonary nodules.After preliminarily verifying the feasibility of the operation in the isolated lung,four beagle dogs were used as animal models to perform puncture localization of the assumed lesions in the upper lobe of the right lung under the guidance of X-ray by using self-designed tracer magnets and puncture instruments,and the positioning effect was observed and evaluated after thorax opening.The operation time required for the tracer magnet implantation,whether there is bleeding at the puncture site,whether the tracer magnet is displaced,and the positioning time of pulmonary nodules after thorax opening were recorded.Results Two tracer magnets were successfully inserted into the upper lobe of the right lung under X-ray guidance in four beagle dogs,and the magnets were successfully attracted and fixed.The median insertion time of the tracer magnet was 5 minutes(4 to 7 minutes),and the insertion process was smooth without bleeding at the puncture site.After thorax opening,oval forceps were used to conveniently locate the location of the tracer magnet,achieving accurate positioning of pulmonary nodules with a median positioning time of 13 seconds(10 to 17 seconds),and the tracer magnet did not shift during the whole process.Conclusion The magnetic tracer technique is simple to operate and pricise for localization of pulmonary nodules.With further optimization of the operation process,this technique is expected to be applied in clinic.
9.Characterisation of whole-brain resting-state functional connectivity in children with Chinese developmental dys-lexia
Dandan LUO ; Min SHEN ; Sujuan WANG ; Wengxin QIU ; Yuxuan ZHANG ; Yun WU ; Shengxiao WANG
Chinese Journal of Rehabilitation Theory and Practice 2025;31(9):1023-1031
Objective To examine resting-state whole-brain network connectivity in children with Chinese developmental dyslexia(DD)and typically developing(TD)children using functional near-infrared spectroscopy(fNIRS).Methods From November to December,2024,19 DD children aged six to twelve years in Children's Hospital of Fudan University were enrolled,along with 18 TD children matching age and sex.Regions of interest included frontal cortex(FC),temporal lobe(TL),occipital lobe(OL)and parietal lobe(PL).Resting-state data were acquired by fNIRS for five minutes in both groups.Functional connectivity strength was calculated at rest,and between-group differences in connectivity strength and brain networks were compared,based on the time series of oxyhe-moglobin concentration.Results The whole-brain functional connectivity strength was higher in DD group than in TD group(t=2.100,P<0.05).Connectivity between the right OL-right FC(t=2.426,P<0.05),right OL-left FC(t=2.483,P<0.05),right TL-right FC(t=2.568,P<0.05)and right TL-left FC(t=2.304,P<0.05)were stonger in DD group than in TD group.The major regions exhibiting differences of whole-brain connectivity between two groups were the right dorsolateral prefrontal cortex,right visual association cortex,right frontal cortex,left orbitofrontal cortex,left visual association cortex,left primary visual cortex and right primary motor cortex.Conclusion Children with DD exhibited significantly stronger connectivity in the right occipital and temporal lobes,as well as between these regions and the prefrontal cortex,suggesting possible right-hemispheric compensation for insufficiency in the left-hemisphere reading network.
10.Research progress of airway epithelial cell senescence mechanism in chronic obstructive pulmonary disease
Zhao-liang LI ; Lue-li WANG ; Qian YI ; Ruo-qiu MA ; Rong GUO ; Chang-li XU ; Xiao-hua DU ; Wei-min YANG
Chinese Pharmacological Bulletin 2025;41(5):805-810
As the first defense of respiratory system,airway epi-thelial cells(AECs)play an important role in separating the re-spiratory internal and external environment.They are essential for the natural immune function.Small airway lesions are an im-portant early pathology of chronic obstructive pulmonary disease(COPD),when AECs are exposed to harmful particles or gases for a long time,the epithelial barrier is damaged,and the signa-ling pathways which involved in differentiation,repair,and in-flammatory are disordered,resulting in epithelial cell cycle stag-nation and accelerated aging.A number of studies have sugges-ted that AECs of COPD patients express high levels of aging markers,suggesting that senescence of AECs is closely related to COPD.This review discusses the potential mechanisms of AECs senescence in COPD,the impact of AECs senescence on the de-velopment and severity of the disease,and highlights potential targets for modulating cellular senescence in airway epithelium as a therapeutic approach in COPD.

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