1.Effect and mechanism of isoliquiritigenin on ferroptosis of chondrocytes in rats with knee osteoarthritis
Shilin CHEN ; Wenheng CHEN ; Guanghui WANG ; Shan GAO
Chinese Journal of Orthopaedics 2025;45(4):230-240
Objective:To investigate the effect and underlying mechanism of isoliquiritigenin (ISL) on chondrocyte ferroptosis in a rat model of knee osteoarthritis (KOA).Methods:Sixty male SD rats were randomly divided into a sham group, KOA group, celecoxib group, ISL low-dose group, and ISL high-dose group. Except for the sham group, KOA models were induced in the other groups using the modified Hulth method. The ISL low-dose and high-dose groups received intraperitoneal injections of 10 mg/kg and 40 mg/kg ISL, respectively; the celecoxib group was orally administered 24 mg/kg celecoxib; the sham and KOA groups received equivalent doses of saline via intraperitoneal injection. Interventions were administered once daily for 8 weeks. Behavioral changes in the open field test, histopathological observations of cartilage, inflammatory cytokine detection, ferroptosis-related indicators, and Sirt1/Nrf2/GPX4 pathway protein expression were measured to determine the optimal ISL dose. Another 60 male SD rats were randomly divided into sham, KOA, ISL high-dose, Sirt1 inhibitor (EX-527), and ISL high-dose + EX-527 groups. KOA models were established in all groups except the sham group. The ISL high-dose group received 40 mg/kg ISL, the EX-527 group received 10 mg/kg EX-527, and the combination group received both. The sham and KOA groups were given saline. Interventions lasted 8 weeks. Histopathological staining evaluated cartilage damage and scoring; ELISA measured tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 levels in synovial fluid; iron deposition, Fe 2+, malonaldehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH) levels were assessed; Western blot analyzed Sirt1/Nrf2/GPX4 pathway proteins; immunohistochemistry detected Collagen II, Aggrecan, MMP-3, and MMP-13 expression. Results:The joint cartilage tissue damage in the ISL low-dose and high-dose rat groups was alleviated compared to the KOA group. The OARSI score, levels of TNF-α, IL-1β and IL-6 in joint fluid, iron deposition in cartilage tissue, Fe 2+, MDA and ROS levels were 8.33±1.86 and 4.50±1.52, respectively. 67.24±7.25 pg/ml, 42.06±5.12 pg/ml; 37.97±4.9 pg/ml, 23.75±4.12 pg/ml; 31.67±4.16 pg/ml, 20.91±3.28 pg/ml; 2.00±0.20, 1.53±0.14; 2.84±0.19 μmol/mg, 1.87±0.16 μmol/mg; 9.11±1.08 nmol/ml, 5.49±1.05 nmol/ml; 759.15±59.80 μmol/ml and 610.85±44.23 μmol/ml were lower than those in KOA group ( P<0.05), and the serum SOD and GSH contents were 12.12±1.52 U/ml and 16.79±2.14 U/ml, respectively. Compared with KOA group, the protein expressions of Sirt1, Nrf2, GPX4 and SLC7A11 were 0.70±0.11 and 0.96±0.13, 0.69±0.10 and 0.95±0.14, 0.51±0.06 and 0.87±0.12, 0.56±0.06 and 0.83±0.10, which were higher than those in KOA group ( P<0.05). The expressions of Acetyl-H4K16, ACSL4, MMP-3 and MMP-13 were 1.68±0.17 and 1.30±0.10, 1.39±0.12 and 0.97±0.10, 1.70±0.14 and 1.10±0.10, 1.64±0.15 and 1.28±0.10, which were lower than those of KOA group ( P<0.05). And the changes of these indexes were higher in Sirt1 inhibitor group. Compared with the ISL high-dose group, the ferroptosis-related indexes were significantly increased in the ISL high-dose+Sirt1 inhibitor group. Conclusion:ISL alleviates articular cartilage injury in KOA rats, and its mechanism is related to activating the Sirt1/Nrf2/GPX4 pathway and inhibiting ferroptosis.
2.Imaging guided percutaneous microwave ablation for unresectable pancreatic cancer:A multicenter retrospective study
Shuilian TAN ; Jie ZHOU ; Ping LIANG ; Xiaoling YU ; Xin YE ; Gang DONG ; Xiang JING ; Guanghui HUANG ; Zhen WANG ; Mengfan PENG ; Yan ZHOU ; Jie YU ; Zhiyu HAN ; Fangyi LIU ; Hongjian GAO ; Yubo ZHANG ; Zhigang CHENG
Chinese Journal of Medical Imaging Technology 2025;41(7):1109-1112
Objective To explore the feasibility and safety of ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer.Methods Totally 84 patients who underwent ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer were enrolled,and the technical success rate,complete ablation rate,complication rate,pain relief rate and survival time,etc.were observed.Results The median age of 84 cases was 61.5 years.Totally 86 tumors,including 44.19%(38/86)at the head/neck and 55.81%(48/86)at the body/tail of pancreas were detected,and a total of 85 ablation sessions were performed with the median ablation energy applied per tumor of 9.90(1.08,21.60)kJ and the complete ablation rate of 42.86%(36/84).The technical success rate was 100%(85/85).Thirty-nine complication events occurred in 25 cases,no ablation-related death.Among 34 patients underwent ablation mainly for pain symptoms,the pain score decreased from(6.22±1.12)points before treatment to(1.94±1.64)points after treatment(P<0.001).During 6.8(3.3,12.9)months' follow-up,the mean survival time was(8.5±6.7)months,and all 47 patients died due to tumor progression.Conclusion Ultrasound-guided percutaneous microwave ablation was safe and feasible for unresectable pancreatic cancer.
3.Evaluation of cardiac function in patients with shock treated by Shenfu injection by ultrasound
Hailan LIU ; Tingting LIU ; Guanghui JIANG ; Zhihui GAO
China Modern Doctor 2025;63(19):51-54,75
Objective To evaluate the therapeutic effect of Shenfu injection in shock patients by using bedside critical ultrasound.Methods A total of 80 shock patients admitted to First Hospital of Nanchang from January 2022 to May 2024 were selected and divided into Shenfu group(45 cases)and control group(35 cases)according to whether Shenfu injection was applied.Patients in control group were given conventional western medical treatment,while patients in Shenfu group were treated with Shenfu injection in addition to control group.The ultrasound measurement indicators and clinical results were recorded on the 1st,3rd,and 7th days of treatment respectively,and left ventricular end diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),peak velocity of early diastolic flow of mitral valve(E)/peak velocity of early diastolic motion of mitral annulus(E'),tricuspid annular plane systolic excusion(TAPSE),right ventricular fractional area change(RVFAC),inferior vena cava variation rate(IVCV),heart rate(HR),mean arterial pressure(MAP),N-terminal pro-brain natriuretic peptide(NT-proBNP),lactic acid(Lac),sequential organ failure assessment(SOFA)score and 30-day survival status of two groups of patients was compared.Results After 1 day,3 days and 7 days of treatment,LVEDD and E/E'of two groups of patients gradually decreased,while LVEF,TAPSE,RVFAC and IVCV gradually increased significantly(P<0.05).After 7 days of treatment,the LVEF,TAPSE,RVFAC and IVCV of patients in Shenfu group were significantly higher than those in control group(P<0.05).After 7 days of treatment,the HR,NT-proBNP,Lac and SOFA scores of two groups of patients were significantly lower than those before treatment in same group,and the MAP was significantly higher than that before treatment in same group(P<0.05).The HR,NT-proBNP,Lac and SOFA scores of patients in Shenfu group were significantly lower than those in control group,the MAP was significantly higher than that in control group,and the mechanical ventilation time and the length of stay in intensive care unit were significantly shorter than those in control group(P<0.05).Kaplan-Meier survival analysis showed that 30-day survival rate of patients in Shenfu group was significantly higher than that in control group(82.22%vs.54.28%,P<0.05).Conclusion Bedside critical ultrasound showed that Shenfu injection could effectively improve ventricular systolic and diastolic function in shock patients,providing a valuable real-time assessment tool for shock treatment.
4.High-throughput circular RNA sequencing reveals tumor-specific high expression of hsa_circ_0001900 in Wilms tumor in association with poor prognosis.
Zhiqiang GAO ; Jie LIN ; Peng HONG ; Zaihong HU ; Kongkong CUI ; Yu WANG ; Junjun DONG ; Qinlin SHI ; Xiaomao TIAN ; Guanghui WEI
Journal of Southern Medical University 2025;45(11):2466-2474
OBJECTIVES:
To explore the expression profile of circular RNAs (circRNAs) and their potential roles in prognosis and progression of Wilms' tumor (WT).
METHODS:
Four pairs of WT and adjacent tissues were collected for high-throughput circRNA sequencing to identify the differentially expressed circular RNAs. RT-qPCR was used to verify the expression levels of the top 6 candidate circRNAs in the clinical samples. hsa_circ_0001900 was selected for analysis of its correlation with clinicopathological features and prognosis in 34 patients with WT. Sanger sequencing and RNase R digestion experiments were used to verify the cycling site and structural stability of hsa_circ_0001900 molecule.
RESULTS:
A total of 23 978 circular RNA molecules were identified in WT tissues by high-throughput circular RNA sequencing, and among them 614 were differentially expressed in WT. hsa_circ_0001900 showed the highest expression level among the differentially expressed circRNAs, which was consistent with the findings in clinical tumor samples and the sequencing results. Correlation analysis showed that hsa_circ_0001900 expression level was positively correlated with WT volume, and the children with high hsa_circ_0001900 expression had a lowered recurrence-free survival rate. The results of Sanger sequencing verified the circular splice site sequence of the molecule, and Rnase R digestion assay confirmed its stable covalent structure.
CONCLUSIONS
This study presents a comprehensive expression profile of circular RNAs in WT, and the expression level of hsa_circ_0001900 is related to the size of WT and the patients' prognosis, suggesting its possible role as a key driving gene in WT progression.
Humans
;
RNA, Circular
;
Wilms Tumor/pathology*
;
Prognosis
;
High-Throughput Nucleotide Sequencing
;
Kidney Neoplasms/genetics*
;
Sequence Analysis, RNA
;
Male
;
Female
5.Strategies for the Syndrome Differentiation and Treatment of Malignant Tumors Based on the Theory of Stagnant Toxin
Luchang CAO ; Ruike GAO ; Manman XU ; Xiaoyu ZHU ; Guanghui ZHU ; Jie LI
Journal of Traditional Chinese Medicine 2025;66(10):1000-1006
"Stagnation" is an important pathological state in the development and progression of malignant tumors. However, its intrinsic connection with different stages of tumor evolution has not been clearly elucidated in previous studies. Drawing on clinical practice, this paper proposes the theory of stagnant toxin, emphasizing stage-specific pathogenesis and differentiated treatment strategies for tumors based on the varying manifestations of stagnation at each phase. The theory interprets the pathogenesis of stagnant toxin across the stages of tumor development through the five elements "wood, fire, earth, metal, and water" corresponding respectively to wood stagnation in the precancerous stage, metal stagnation in the postoperative phase, fire stagnation during adjuvant therapy, earth stagnation in the progressive stage, and water stagnation in the advanced stage. Each type of stagnation reflects a distinct pathogenic mechanism, such as wood stagnation giving rise to disease, metal stagnation inducing residual symptoms, fire stagnation resulting in ulceration, earth stagnation spreading toxin transmission, and water stagnation leading to critical deterioration. Accordingly, the treatment principles include guiding wood stagnation with counterflow, dispersing metal stagnation to harmonize symptoms, venting fire stagnation to regress ulcers, depleting earth stagnation to block progression, and controlling water stagnation to preserve vitality. This theoretical framework offers a traditional Chinese medicine perspective for understanding and treating malignant tumors based on the concept of stagnant toxin.
6.Postoperative Stage-based Functional Protection Strategies for Lung Cancer Based on Theory of "Lungs Governing Qi"
Luchang CAO ; Guanghui ZHU ; Ruike GAO ; Manman XU ; Xiaoyu ZHU ; Wei HOU ; Ying ZHANG ; Jie LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):86-93
Lung cancer (LC) is a significant global public health issue, with both its incidence and mortality rates ranking among the highest worldwide. The age-standardized incidence and mortality rates are increasing annually, posing a serious threat to the life and health of LC patients. Radical surgical resection is the primary treatment for malignant lung tumors. However, postoperative multidimensional functional impairments, including respiratory, mucosal, and psychological functions, are common. These impairments not only reduce patients' quality of life and affect their treatment tolerance and duration, but also negatively correlate with prognosis, facilitating disease recurrence and metastasis. At present, postoperative functional dysfunction after LC surgery remains a key clinical challenge that urgently needs to be addressed. There is a lack of standardized and regulated postoperative rehabilitation treatment management and traditional Chinese medicine (TCM) differentiation and treatment strategies for LC. Focusing on the core underlying pathogenesis of "Qi sinking" after LC surgery, and guided by the classical TCM theory of "lungs governing Qi", this study, based on the core concept of the "five perspectives on treatment" theory, innovatively proposes the respiratory dysfunction as the core pathogenesis of "Qi sinking in the chest" during the rapid rehabilitation phase, mucosal dysfunction as the core pathogenesis of "Yin deficiency and Qi sinking" during the postoperative adjuvant treatment phase, and the psychological dysfunction as the core pathogenesis of "Qi sinking with emotional constraint" during the consolidation phase. Accordingly, stage-specific dynamic functional protection strategies are constructed. In the rapid rehabilitation phase, the strategy emphasizes tonifying Qi and uplifting sinking Qi, with differentiation and treatment based on the principle of ''descending before ascending''. In the adjuvant treatment phase, the approach focuses on nourishing Yin and uplifting Qi, with prescription combinations that integrate unblocking and tonification. In the consolidation phase, the strategy aims to resolve constraint and uplift Qi, with clinical treatment emphasizing a combination of dynamic and static methods. At each stage of functional rehabilitation, clinical differentiation and treatment should support healthy Qi and eliminate pathogenic factors simultaneously. This study is the first to propose the concept of postoperative functional protection in TCM, offering a new approach for TCM differentiation and treatment in the full-cycle, stage-based, and dynamic protection of postoperative function in LC patients. It is expected to contribute to the construction and development of an integrated TCM-Western medicine comprehensive program for cancer prevention and treatment in China.
7.A Hierarchical Strategy for Differentiation and Treatment of Recurrent Aphthous Oral Ulcers Related to Targeted Therapy for Lung Cancer Based on Yin Deficiency and Qi Collapse
Luchang CAO ; Guanghui ZHU ; Ruike GAO ; Manman XU ; Xiaoyu ZHU ; Ming LIN ; Ying ZHANG ; Jie LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):116-125
Tumor treatment-related adverse reactions are a major focus of clinical concern, among which recurrent aphthous oral ulcers (RAU) associated with targeted therapy for lung cancer (LC) are among the most painful and distressing for patients. Currently, modern medical interventions show limited efficacy, and there is an urgent need for more effective treatment strategies. This study differentiates RAU associated with targeted therapy for LC from chemotherapy-related and ordinary oral ulcers, elucidates the pathophysiological basis of such ulcers, and traces the theoretical origin of "Yin deficiency and Qi collapse". Based on the new system of "five perspectives on diagnosis and treatment" for tumor prevention and treatment, with a focus on the core and symptom perspectives and rooted in the traditional concept of "lung dominating Qi", we innovatively propose the concept of "medicine-induced ulcer" and are the first to introduce the theory of "Yin deficiency and Qi collapse" into the syndrome differentiation and treatment of RAU associated with targeted therapy for LC (i.e., medicine-induced ulcer). We propose that "Yin deficiency and Qi collapse" is the core pathogenesis of medicine-induced ulcers, in which the collapse of formless Qi is the key to their onset, while the deficiency and stasis of tangible Yin and blood constitute the root of recurrence. A hierarchical strategy for syndrome differentiation and treatment is established: first treating the collapse of formless Qi, then replenishing tangible deficiencies, and concurrently preventing recurrence. We emphasize that treatment should address both root and manifestation, with appropriate prioritization. In the acute phase, while relieving symptoms and promoting ulcer healing by nourishing Qi, uplifting collapse, and generating body fluids, attention should also be paid to nourishing spleen Yin, facilitating the circulation of nutritive Qi, and alleviating stasis to target the root pathogenesis and reduce recurrence. A verified case is presented to support this approach. This study enriches the theoretical framework and clinical methods of traditional Chinese medicine (TCM) in the treatment of RAU associated with targeted therapy for LC, promotes symptom management of treatment-related adverse reactions through integrated TCM and Western medicine, and provides theoretical support for the construction and development of a comprehensive differentiation and treatment system for lung cancer prevention, treatment, and rehabilitation.
8.Development of a risk prediction model for cancer-related cognitive impairment in lung cancer patients from the perspective of precision health in nursing science
Xiaoyu XU ; Lei YE ; Fangmei CHEN ; Pan GAO ; Guanghui XIA
Chinese Journal of Practical Nursing 2025;41(14):1063-1071
Objective:Predictive modelling of risk of cancer-related cognitive impairment (CRCI) in lung cancer patients from the perspective of precision health in nursing science.Methods:Prospectively collected lung cancers treated in the Department of Respiratory Medicine of Affiliated Nanjing Brain Hospital, Nanjing Medical University from October 2023 to April 2024 as study subjects by a convenience samphing method. Lasso regression was used to screen the characteristic variables and construct the prediction model, and the predictive ability was evaluated by the AUC of the subjects′operating characteristics; Bootstrap resampling (1 000 times) internal validation of the model; the Hosmer-Lemeshow goodness-of-fit test was performed and the calibration curve was plotted to evaluate the calibration of the model; the clinical validity of the model was evaluated by decision cure analysis (DCA).Results:A total of 142 patients with lung cancer were included, 94 males and 38 females. The incidence of CRCI in lung cancer patients was 69.7%(99/142). Lasso regression showed that age(≥65), education, tumor stage, serum albumin, and PLR were independent risk factors for CRCI (coefficients of 0.372 048 72, - 0.361 265 78, 0.068 728 00, - 0.039 940 32, 0.001 639 92 respectively). The model AUC was 0.874 (95% CI: 0.815-0.933), with a sensitivity of 0.768, and a specificity of 0.860; the H-L goodness-of-fit test showed good agreement ( χ2 = 4.51, P>0.05), and Bootstrap re-sampling internal validation showed an AUC of 0.826. Calibration curves showed good agreement and accuracy between the model predicted probabilities and the actual observed probabilities. DCA showed that the model had clinical benefit when the threshold probability was approximately>25%. Conclusions:The CRCI column-line diagram risk model constructed in this study has good predictive efficacy and can effectively predict the occurrence of CRCI in lung cancer patients.
9.PE_PGRS37 protein promotes intracellular colonization of Mycobacterium tuberculosis by inhibiting macrophage autophagy flow
Mengyu LI ; Zhenjun ZHANG ; Tingting FENG ; Hui WANG ; Chanchan NIE ; Chunwen CHEN ; Yunjie GAO ; Yifan DUAN ; Ruonan GUO ; Yingying CUI ; Guanghui DANG ; Siguo LIU
Chinese Journal of Zoonoses 2025;41(10):1005-1010,1015
This study explored the effect of the Mycobacterium tuberculosis(Mtb)PE/PPE family protein PE_PGRS37 on the growth of Mycobacterium smegmatis(Ms)and macrophage autophagy during Mtb infection.The pe_pgrs37 gene was amplified from Mtb genome through PCR,and the recombinant vector pAIN-PE_PGRS37 was successfully constructed through homologous recombi-nation.pAIN-PE_PGRS37 and pAIN were integrated into Ms through electroshock to construct pAIN-PGRS37/Ms and pAIN/Ms re-combinant bacteria.Western blotting indicated that the PE_PGRS37 protein was correctly expressed in pAIN-PE_PGRS37/Ms.The re-combinant bacteria were inoculated in 7H9/7H10 medium,and their colony morphology and growth curves were observed.No signifi-cant difference in colony morphology was observed between pAIN-PE_PGRS37/Ms and pAIN/Ms.The growth rate significantly in-creased between 10 and 16 h,and a plateau was reached at 26 h.After infection of U937 cells with pAIN-PE_PGRS37/Ms and pAIN/Ms,macrophage autophagy flow was detected with western blotting and immunofluorescence.In the pAIN-PE_PGRS37/Ms-infected group,compared with the pAIN/Ms-infected group,macrophage LC3-II and p62 protein expression was significantly up-regulated(P<0.001)and inhibited autophagosome and lysosome fusion.The intracellular survival of the recombinant bacteria was detected through colony counting,and pAIN-PE_PGRS37/Ms showed significantly greater survival in macrophages at 12 h,24 h,and 48 h than pAIN/Ms(P<0.05).Our results suggested that PE_PGRS37 protein promotes Mycobacterium survival in macrophages by blocking macro-phage autophagy flow,thus inhibiting macrophage autophagy.
10.Development of a risk prediction model for cancer-related cognitive impairment in lung cancer patients from the perspective of precision health in nursing science
Xiaoyu XU ; Lei YE ; Fangmei CHEN ; Pan GAO ; Guanghui XIA
Chinese Journal of Practical Nursing 2025;41(14):1063-1071
Objective:Predictive modelling of risk of cancer-related cognitive impairment (CRCI) in lung cancer patients from the perspective of precision health in nursing science.Methods:Prospectively collected lung cancers treated in the Department of Respiratory Medicine of Affiliated Nanjing Brain Hospital, Nanjing Medical University from October 2023 to April 2024 as study subjects by a convenience samphing method. Lasso regression was used to screen the characteristic variables and construct the prediction model, and the predictive ability was evaluated by the AUC of the subjects′operating characteristics; Bootstrap resampling (1 000 times) internal validation of the model; the Hosmer-Lemeshow goodness-of-fit test was performed and the calibration curve was plotted to evaluate the calibration of the model; the clinical validity of the model was evaluated by decision cure analysis (DCA).Results:A total of 142 patients with lung cancer were included, 94 males and 38 females. The incidence of CRCI in lung cancer patients was 69.7%(99/142). Lasso regression showed that age(≥65), education, tumor stage, serum albumin, and PLR were independent risk factors for CRCI (coefficients of 0.372 048 72, - 0.361 265 78, 0.068 728 00, - 0.039 940 32, 0.001 639 92 respectively). The model AUC was 0.874 (95% CI: 0.815-0.933), with a sensitivity of 0.768, and a specificity of 0.860; the H-L goodness-of-fit test showed good agreement ( χ2 = 4.51, P>0.05), and Bootstrap re-sampling internal validation showed an AUC of 0.826. Calibration curves showed good agreement and accuracy between the model predicted probabilities and the actual observed probabilities. DCA showed that the model had clinical benefit when the threshold probability was approximately>25%. Conclusions:The CRCI column-line diagram risk model constructed in this study has good predictive efficacy and can effectively predict the occurrence of CRCI in lung cancer patients.

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