1.Quercetin ameliorates myocardial injury in diabetic rats by regulating L-type calcium channels.
Hongyan SUN ; Guoqing LU ; Chengwen FU ; Mengwen XU ; Xiaoyi ZHU ; Guoquan XING ; Leqiang LIU ; Yufei KE ; Lemei CUI ; Ruiyang CHEN ; Lei WANG ; Pinfang KANG ; Bi TANG
Journal of Southern Medical University 2025;45(3):531-541
OBJECTIVES:
To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats.
METHODS:
Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique.
RESULTS:
The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin.
CONCLUSIONS
Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals
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Quercetin/pharmacology*
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Calcium Channels, L-Type/metabolism*
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Diabetes Mellitus, Experimental/metabolism*
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Rats, Sprague-Dawley
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Rats
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Myocytes, Cardiac/drug effects*
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Myocardium/pathology*
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Male
2.Tongue squamous cell carcinoma-targeting Au-HN-1 nanosystem for CT imaging and photothermal therapy.
Ming HAO ; Xingchen LI ; Xinxin ZHANG ; Boqiang TAO ; He SHI ; Jianing WU ; Yuyang LI ; Xiang LI ; Shuangji LI ; Han WU ; Jingcheng XIANG ; Dongxu WANG ; Weiwei LIU ; Guoqing WANG
International Journal of Oral Science 2025;17(1):9-9
Tongue squamous cell carcinoma (TSCC) is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion. Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients. The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy. Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC. However, inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy (PTT). This study modified gold nanodots (AuNDs) with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT. The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuNDs. The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC. Moreover, owing to its stable long-term fluorescence and high X-ray attenuation coefficient, the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC, rendering it useful for early tumor detection and accurate delineation of surgical margins. In conclusion, Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.
Tongue Neoplasms/diagnostic imaging*
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Carcinoma, Squamous Cell/diagnostic imaging*
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Animals
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Gold/chemistry*
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Mice
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Photothermal Therapy/methods*
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Tomography, X-Ray Computed
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Photosensitizing Agents
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Metal Nanoparticles
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Humans
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Cell Line, Tumor
3.Effects of sacral neuromodulation on urodynamic parameters during the storage phase in patients with neurogenic bladder
Haichao LIU ; Guoqing CHEN ; Peng ZHANG ; Fan ZHANG ; Baihui WANG ; Fei ZHOU ; Yanhe JU
Journal of Modern Urology 2025;30(12):1075-1079
Objective To explore the effects of sacral neuromodulation (SNM) on urodynamic parameters during the storage phase in patients with neurogenic bladder (NB), so as to provide reference for evaluating the efficacy of SNM. Methods A total 49 NB patients undergoing SNM at our hospital during Oct.2012 and May 2025 were enrolled. Baseline data and video-urodynamic parameters were collected. Changes in maximum cystometric capacity, maximum detrusor pressure during storage phase, and bladder compliance before and after treatment were assessed. Improvements in detrusor overactivity (DO) and vesicoureteral reflux (VUR) were also analyzed. Results Among the 49 patients,27 were male and 22 were female, with a mean age of (37.41±15.15) years, a median disease duration of 5.0 (2.0,15.5) years, and a median follow-up of 11 (1,32) months. Up to 37 patients (75.5%) received permanent sacral nerve pulse generator implantation (permanent implant group), while the remaining 12 were classified as the non-permanent implant group. Before and after the test period, all patients showed a significant increase in maximum cystometric capacity [ (218.0 (93.0,358.5) mL vs.300.0 (238.5, 400.0) mL, P<0.001], a decrease in maximum detrusor pressure during the filling phase [32.0 (13.5,71.0) cmH_2 O vs. 20.0 (9.0,50.0) cmH_2 O, P<0.001], and an improvement in bladder compliance [11.8 (8.3,25.6) mL/cmH_2 O vs.26.7 (8.6,44.1) mL/cmH_2O, P<0.001]. In the permanent implant group, comparisons before and after the test period showed an increase in maximum bladder capacity [ (239.16±147.23) mL vs. (312.24±121.83) mL, P<0.001], a decrease in maximum detrusor pressure during filling[32.0 (15.0,58.0) cmH_2 O vs.15.0 (9.0,41.0) cmH_2 O, P<0.05], and improved bladder compliance [10.8 (8.3,23.6) mL/cmH_2 O vs.28.6 (8.6,41.4) mL/cmH_2 O, P<0.001]. No statistically significant differences in these parameters before and after the test period were observed in the non-permanent implant group (P>0.05). A total of 17 patients in the permanent implant group underwent follow-up video urodynamics. Compared to pre-test values, significant improvements were observed in maximum detrusor pressure during filling, and bladder compliance both at the end of the test period and at the last follow-up (P<0.05). However, no statistically significant differences were found in maximum cystometric capacity, maximum detrusor pressure during filling, and bladder compliance between the end of the test period and the last follow-up (P>0.05). Among the 49 patients,21 had DO and 20 had VUR. Both DO and VUR showed improvement after the test period and at the last follow-up. Conclusion SNM can effectively improve storage function in NB patients, ameliorate detrusor overactivity and bladder compliance, and relieve or eliminate VUR in some patients. Long-term follow-up confirms that SNM provides stable therapeutic effects, demonstrating significant clinical value.
4.Pathogenomic surveillance of Bordetella pertussis clinical isolates in Liaocheng City, Shandong Province in 2024
Jinli JIA ; Jie CHE ; Lili ZHENG ; Jinzhong ZHANG ; Hong LIU ; Rui YANG ; Guoqing LI ; Xiaoshuang LU ; Hui YUAN
Chinese Journal of Preventive Medicine 2025;59(11):1848-1854
Objective:To analyze the molecular characteristics of prevalent Bordetella pertussis (Bp) isolates in Liaocheng City, Shandong Province in 2024. Methods:From March to August 2024, oropharyngeal swabs were collected from suspected pertussis cases at Liaocheng People′s Hospital in Shandong Province for Bp isolation. A total of 99 Bp isolates were obtained. Whole-genome sequencing was performed on all isolates, followed by Multilocus Sequence Typing (MLST), vaccine antigen-related gene typing (including ptxP, ptxA, ptxB, ptxC, ptxD, ptxE, fhaB, fim2, fim3, and prn), 23S rRNA gene typing, and phylogenetic analysis. To capture the differences between Bp isolates and vaccine strains in Liaocheng City, the international vaccine strain Tohama I and the Chinese vaccine strain CS were included in the analysis. Antimicrobial resistance testing against 11 agents was performed on 52 isolates. Results:The throat swabs of 99 Bp isolates were collected from patients aged 44 days to 42 years, and the median age of the patients was 7 (5, 8) years. All isolates ptxP were ptxP3 type. 74 isolates (74.75%) carried the prn150, while 21 isolates (21.21%) were prn-deficient. The predominant antigenic profile was ptxP3/ ptxA1/ ptxB1/ ptxC4/ ptxD1/ ptxE4/ fhaB1/ fim2-1/ fim3-1/ prn150, found in 72 isolates (72.73%). All 99 isolates carried the A2047G mutation in the 23S rRNA gene. Antimicrobial susceptibility testing showed that the MICs of macrolides and clindamycin for all 52 Bp isolates were all >256 mg/L. However, the isolates showed low MIC for seven other antimicrobials tested, including trimethoprim-sulfamethoxazole, amoxicillin, and levofloxacin. MLST typing revealed that 94 isolates (94.95%) were identified as ST-2, while 5 isolates (5.05%) belonged to a novel sequence type (ST-118). Phylogenetic analysis demonstrated that all 99 Bp isolates were highly homologous but clustered in evolutionary branches distinct from vaccine strains. Conclusion:In 2024, Bordetella pertussis isolates in Liaocheng City exhibit distinct clonal epidemic characteristics, with the predominant antigenic genotype being ptxP3/ ptxA1/ ptxB1/ ptxC4/ ptxD1/ ptxE4/ fhaB1/ fim2-1/ fim3-1/ prn150. All isolates are resistant to macrolide antibiotics.
5.Correlation between MA and knee FA in X-ray imaging for axial position of patellofemoral joint on the basis of dynamic adjustment device
Huawen QI ; Guoqing LIU ; Yi YI ; Zhuozhao ZHENG
China Medical Equipment 2025;22(10):26-29
Objective:To investigate the correlation between the set mechanical angle(MA)by using an auxiliary photography device and the actual knee flexion angle(FA)in axial X-ray imaging for patellofemoral joint,so as to provide a theoretical basis for applying a self-developed dynamic adjustment device to achieve precisely dynamic radiography for patellofemoral joint,and to optimize diagnostic protocols of imaging for patellar dislocation,subluxation,etc..Methods:A prospective experimental design was adopted,which enrolled 96 healthy volunteers(40 males,56 females)whose age was 18-65 years old(mean age:32.6 years old).Using a self-developed dynamically auxiliary radiography device for axial position of patellofemoral joint,and the MA was set at 90°,120°,135°,150°,and 160°,and the corresponding FA was measured.At the same time,the gender,age,body mass index(BMI),thigh circumference,and calf circumference were also recorded.Statistical analysis was performed using SPSS 25.0 software.One-sample t-test was applied to analyze the difference value between MA and FA(MA-FA).Pearson correlation analysis and multiple linear regression analysis were conducted to conduct correlation analysis for the distribution characteristics of FA under different MA values,the FA and each anthropometric indicator.Results:FA showed a linear relationship with MA,BMI,thigh circumference,calf circumference,and gender.The regression equation was:FA=62.031+0.511×MA+0.489×BMI+0.189×thigh circumference-0.445×calf circumference+4.67×gender(R2=0.82,P<0.001).When MA was set at 90°,The actual FA was(112.21±4.7)° that was significantly larger than MA(90°),and the difference was significant(t=46.26,P<0.001).When MA was set at 120°,the actual FA was(126.19±6.43°),which was significantly greater than MA(120°)(t=9.42,P<0.001).When MA was set at 135°,there was not significant difference between FA and MA(P>0.05).When MA was set at 150°,the actual FA was(141.44±4.42°)that was significantly smaller than MA(150°),and the difference was significant(t=-18.97,P<0.001).When MA was set at 160°,the actual FA was(148.55±5.33°)that was significantly smaller than MA(160°),and the difference was significant(t=-21.03,P<0.001).BMI,thigh circumference,and calf circumference were the main factors of influencing the difference between MA and FA.Conclusion:Using the self-developed dynamic auxiliary radiography device for axial position of patellofemoral joint can construct a mathematical model to accurately predict,regulate and control the knee flexion angle,which can realize standardization for dynamic radiography on patellofemoral joint,and has significant clinical value in improving the diagnostic accuracy for imaging of patellar dislocation and subluxation.
6.Predictive value of pre-treatment circulating tumor DNA genomic landscape in patients with relapsed/refractory multiple myeloma undergoing anti-BCMA CAR-T therapy: Insights from tumor cells and T cells
Rongrong CHEN ; Chunxiang JIN ; Kai LIU ; Mengyu ZHAO ; Tingting YANG ; Mingming ZHANG ; Pingnan XIAO ; Jingjing FENG ; Ruimin HONG ; Shan FU ; Jiazhen CUI ; Simao HUANG ; Guoqing WEI ; He HUANG ; Yongxian HU
Chinese Medical Journal 2025;138(19):2481-2490
Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.
7.Catheter-directed thrombolysis for acute entire lower extremity deep venous thrombosis: a comparative study of calf deep vein and contralateral femoral venous access
Jian WANG ; Cheng QIAN ; Guoqing NI ; Maofeng GONG ; Liang LIU ; Peng PENG ; Libing GAO ; Jianping GU ; Guoping CHEN
Chinese Journal of Radiology 2025;59(5):577-585
Objective:To compare the clinical efficacy of catheter-directed thrombolysis (CDT) via the contralateral femoral vein approach (CFVA-CDT) and the calf deep vein approach (CVA-CDT) in the treatment of acute mixed-type lower extremity deep vein thrombosis (DVT).Methods:Patients treated with CFVA-CDT and CVA-CDT for acute mixed-type DVT were retrospectively collected from January 2018 to December 2021, totaling 49 and 32 patients, respectively. The relevant technical indicators, thrombolysis rates in the iliac-femoral vein segment and femoral-popliteal vein segment, clinical efficacy, and the incidence of lower extremity deep vein patency, venous valve insufficiency, and post-thrombotic syndrome (PTS), as well as the severity of chronic venous disease in the affected limb (VCSS score) during a 2-year follow-up period were retrospectively compared between the two venous access CDT groups. The t-test was used for comparing quantitative data, while the chi-square test or Fisher′s exact test was used for categorical data.Results:During CFVA-CDT procedure, 6-8 F vascular sheaths were used, and balloon dilation of 2~6 mm was more frequently employed (65.31%, 32/49) to expand venous stenosis/occlusion segments before successful sheath placement compared to the CVA-CDT group (37.50%, 12/32), and the difference was statistically significant ( P=0.014). In the CVA-CDT group, 31.25% (10/32) of patients had a maximum sheath size of 6 F, while the remainder used 4 or 5 F sheaths. Among them, 34.38% (11/32) of patients required re-puncture of the popliteal or femoral vein for larger sheaths (≥8 F) for thrombus aspiration and subsequent endovascular treatment during or after thrombolysis. The effective thrombolysis rates (≥50%) in the iliac-femoral vein segment were not significantly different between the two groups ( P=0.778). The effective thrombolysis rate of the femoral-popliteal venous segment is related to the presence or absence of popliteal vein opacification on lower extremity venous antegrade venography. There was no significant difference between the groups when the popliteal vein was visualized ( P=1.000). While the popliteal vein was not visualized, the CVA-CDT group (75.0%, 15/20) was significantly better than the CFVA-CDT group (34.38%, 11/32), and the difference was statistically significant ( P=0.004). There was no significant difference in clinical efficacy between the two groups ( P=0.819). During follow-up, the femoral-popliteal vein patency rate in the CVA-CDT group (87.50%, 28/32) was significantly higher than in the CFVA-CDT group (44.90%, 22/49), the difference was statistically significant ( P<0.001). Conclusions:Successful CFVA-CDT requires the assistance of more ancillary devices, while the use of larger sheaths is more limited in CVA-CDT due to the smaller caliber of the calf deep veins. The presence or absence of popliteal vein opacification on lower extremity venous antegrade venography may influence the effective thrombolysis of the femoral-popliteal venous segment thrombus in patients with acute mixed deep vein thrombosis (DVT) treated with CFVA-CDT and CVA-CDT. Compared to CFVA-CDT, CVA-CDT can improve the patency rate of the femoral-popliteal venous segment.
8.Multi dimensional assessment study on the accuracy and clinical application of mainstream and sidestream monitoring technologies for partial pressure of end tidal carbon dioxide in monitoring devices
Sheng CHENG ; Fei WANG ; Guoqing WANG ; Nanhai WANG ; Dehao ZHU ; Zhijie LIU
China Medical Equipment 2025;22(8):1-6,16
Objective:To investigate the measurement differences between mainstream and sidestream partial pressure of end tidal carbon dioxide(PetCO2)monitoring techniques in mechanically ventilated patients,as well as the correlation with partial pressure of arterial blood carbon dioxide(PaCO2)and clinical applicability,and to provide a basis for the rational selection of monitoring methods in the clinic.Methods:A total of 169 patients who underwent invasive mechanical ventilation in the operating room of the First Affiliated Hospital of Bengbu Medical University from August to November 2024 were selected to be monitored by three monitoring techniques of mainstream PetCO2,sidestream PetCO2 and PaCO2,respectively,and the 243 sets of valid pairwise data monitored by the three monitoring techniques were recorded,analyzed for correlation and deviation,and performed PaCO2 and PetCO2 were stratified and analyzed.Likert scales were used to analyze the subjective ratings of the 3 monitoring techniques of mainstream PetCO2,sidestream PetCO2,and PaCO2 by the 31 health care professionals who used the study.Results:Both mainstream and sidestream PetCO2 correlated with PaCO2(r=0.554,0.515,P<0.05),and mainstream PetCO2 correlated better than sidestream;mainstream PetCO2 was lower than the concurrent PaCO2 by 6.00 mmHg,and the 95%limit of agreement(95%LoA)was±6.28 mmHg,both lower than that of sidestream by 8.24 mmHg and±7.41 mmHg.8.24 mmHg and±7.41 mmHg.The dispersion of sidestream PetCO2 monitoring values was greater,especially at high PaCO2 levels.Mainstream method PetCO2 had the highest correlation with PaCO2 in gynecologic patients(r=0.820,P<0.05),and sidestream method PetCO2 underestimated PaCO2 more markedly in gastrointestinal and hepato-biliary-pancreatic surgery patients.The deviation of oxygenation index≤300 mmHg was significantly greater than that of patients with oxygenation index>300 mmHg,and the tendency of underestimation was more significant at high PaCO2.31 healthcare experts evaluated that the mainstream PetCO2 monitoring method was outstanding in terms of accuracy and real-time,and that the sidestream method of PetCO2 monitoring was advantageous in terms of ease of operation and management of consumables.Conclusion:In patients who receive mechanical ventilation,the precision,accuracy and real-time of mainstream PetCO2 monitoring are better,which is suitable for patients with rapid changes in disease condition or patients at risk of hypercapnia.The sidestream method is suitable for non-intubated or transported patients,but it is easy to be underestimated at high PaCO2,and it needs to be corrected regularly in combination with arterial blood gas.The clinical application should rationally choose monitoring method after a comprehensive assessment based on the patient's disease condition,oxygenation status,and the scenario of use.
9.Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury (version 2025)
Aijun XU ; Shuixia LI ; Bo CHEN ; Mengyuan YE ; Lejiao LANG ; Ning NING ; Lin ZHANG ; Changqing LIU ; Zhonglan CHEN ; Weihu MA ; Weishi LI ; Xiaoning WANG ; Dongmei BIAN ; Jiancheng ZENG ; Xin WANG ; Yuan GAO ; Yaping CHEN ; Jiali CHEN ; Yun HAN ; Xiuting LI ; Yang ZHOU ; Xiaojing SU ; Qiong ZHANG ; Tianwen HUANG ; Ping ZHANG ; Hua LIN ; Xingling XIAO ; Ruifeng XU ; Fanghui DONG ; Bing HAN ; Luo FAN ; Yanling PEI ; Suyun LI ; Xiaoju TAN ; Rongchen GUO ; Yefang ZOU ; Xiaoyun HAN ; Junqin DING ; Yi WANG ; Shuhua DENG ; Jinli GUO ; Yinhua LIANG ; Yuan CEN ; Xiaoqin LIU ; Junru CHEN ; Haiyang YU ; Lunlan LI ; Ying REN ; Yunxia LI ; Jianli LU ; Ying YING ; Lan WEI ; Yin WANG ; Qinhong XU ; Yanqin ZHANG ; Yang LYU ; Shijun ZHANG ; Sui WENJIE ; Sanlian HU ; Shuhong YANG ; Guoqing LI ; Jingjing AN ; Baorong HE ; Leling FENG
Chinese Journal of Trauma 2025;41(6):530-541
Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.
10.Total flavonoids of Pterocarya hupehensis Skan alleviate DSS-induced ul-cerative colitis in mice by modulating macrophage polarization
Guoqing CHEN ; Xiaorong LIU ; Jin JIN ; Dong YAN ; Renjia LIU ; Shan XIANG ; Lin YUAN ; Yang XIANG ; Hao WU ; Xiulan SHEN
Chinese Journal of Pathophysiology 2025;41(6):1181-1189
AIM:To investigate the effects of total flavonoids of Pterocarya hupehensis Skan(PHSTF)on dex-tran sulfate sodium(DSS)-induced ulcerative colitis(UC)mouse model and lipopolysaccharide(LPS)-stimulated RAW264.7 macrophages.METHODS:Thirty-six male C57BL/6J mice(6 to 8 weeks old,SPF grade)were randomly di-vided into 6 groups:negative control(NC)group,3%DSS-induced model group,mesalazine(300 mg·kg-1·d-1)group,and low-dose(62.5 mg·kg-1·d-1),medium-dose(125 mg·kg-1·d-1)and high-dose(250 mg·kg-1·d-1)PHSTF treatment groups,with 6 mice in each group.The mice in NC group received distilled water,while those in other groups were treated with a 3%DSS solution for 7 d to induce the UC model.On the 1st day of DSS administration,the mice in treatment groups received the corresponding agents via oral gavage for 10 d,while those in NC and model groups were gavaged with distilled water.Throughout the study,the effects of PHSTF on body weight,fecal blood,and colon length were measured and recorded daily.Histopathological changes in colon tissues were assessed using hematoxylin-eosin staining.The levels of the pro-inflammatory cytokine interleukin-1β(IL-1β)and the anti-inflammatory cytokine IL-10 in colon tissues were quantified using ELISA.The LPS-induced RAW264.7 macrophage model was employed to evaluate the cellular effects of PHSTF.Cell viability was assessed by CCK-8 assay,and cell morphology was observed under a microscope.The mRNA expression of inflammatory markers[IL-1β,inducible nitric oxide synthase(iNOS),IL-10 and arginase-1(Arg-1)]was measured by RT-qPCR.Western blot and immunofluorescence double labeling were used to detect the protein expression of macrophage polarization markers(iNOS,CD206 and Arg-1).Finally,immunohistochemistry(IHC)was utilized to as-sess protein expression of iNOS in colon tissues.RESULTS:Compared to the DSS-induced UC model group,PHSTF sig-nificantly improved several parameters,including weight loss(P<0.05),rectal bleeding,and colon shortening in DSS-treated mice.PHSTF also reduced histopathological damage and inflammatory cell infiltration in the colon.It decreased IL-1β levels(P<0.05)and increased IL-10 levels(P<0.05)in colon tissues.In LPS-induced RAW264.7 cells,PHSTF reduced the mRNA expression of IL-1β and iNOS(P<0.01),while upregulating the mRNA expression of IL-10 and Arg-1(P<0.01).Additionally,PHSTF decreased iNOS protein expression(P<0.01)and elevated the expression of Arg-1 and CD206 proteins(P<0.01).IHC analysis further confirmed that PHSTF downregulated iNOS protein expression in colon tissues.CONCLUSION:Treatment with PHSTF promotes the polarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype,thereby alleviating inflammation in colon tissue and ameliorating ulcer-ative colitis in mice.

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