1.Oxymatrine,a novel TLR2 agonist,promotes megakaryopoiesis and thrombopoiesis through the STING/NF-κB pathway
Chengyang NI ; Ling ZHOU ; Shuo YANG ; Mei RAN ; Jiesi LUO ; Kui CHENG ; Feihong HUANG ; Xiaoqin TANG ; Xiang XIE ; Dalian QIN ; Qibing MEI ; Long WANG ; Juan XIAO ; Jianming WU
Journal of Pharmaceutical Analysis 2025;15(1):208-229
Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxy-matrine,a new molecule capable of healing RIT was screened out,and the underlying regulatory mecha-nism associated with magakaryocyte(MK)differentiation and thrombopoiesis was demonstrated.The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro.The ability to induce thrombopoiesis was subsequently demonstrated in Tg(cd41:enhanced green fluorescent protein(eGFP))zebrafish and RIT model mice.In addition,we carried out network pharmacological pre-diction,drug affinity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)analyses to explore the potential targets of oxymatrine.Moreover,the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,Western blot(WB),and immunofluorescence.Oxymatrine markedly promoted MK differentiation and maturation in vitro.Moreover,oxymatrine induced thrombopoiesis in Tg(cd41:eGFP)zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice.Mechanistically,oxymatrine directly binds to toll-like receptor 2(TLR2)and further regulates the downstream pathway stimulator of interferon genes(STING)/nuclear factor-kappaB(NF-κB),which can be blocked by C29 and C-176,which are specific inhibitors of TLR2 and STING,respectively.Taken together,we demonstrated that oxymatrine,a novel TLR2 agonist,plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis,suggesting that oxymatrine is a promising candidate for RIT therapy.
2.Effect of DExH-box helicase 9 O-GlcNAc modification on the proliferation of HBV-associated hepatoma cells
Huimin LUO ; Yubo PI ; Yanmeng CHEN ; Kai WANG ; Ni TANG ; Ailong HUANG
Journal of Chongqing Medical University 2025;50(6):799-807
Objective:To investigate the effect of DExH-box helicase 9(DHX9)O-linked N-acetylglucosamine(O-GlcNAc)modifi-cation(O-GlcNAcylation)on the proliferation of hepatitis B virus(HBV)-associated hepatoma cells.Methods:The pAdTrack-TO4-DHX9-3Flag recombinant adenovirus plasmid was constructed by molecular cloning and transfected into HEK293 cells for packaging and amplification of the recombinant adenovirus AdDHX9.The interaction between DHX9 and O-GlcNAc transferase(OGT)was con-firmed using co-immunoprecipitation.The co-localization between DHX9 and OGT was measured by immunofluorescence.The level of DHX9 O-GlcNAcylation was determined using succinylated wheat germ agglutinin(sWGA)and glycosylated immunoprecipitation(IP).The effect of DHX9 O-GlcNAcylation on the proliferation of HBV-associated hepatoma cells was assessed using the colony-forming assay and cell growth curves.Results:The recombinant adenovirus AdDHX9 was successfully obtained,and DHX9 expression was confirmed by Western blot.DHX9 interacted with OGT,and the two proteins were co-localized on the nucleus.The sWGA and gly-cosylated IP experiments showed that DHX9 underwent O-GlcNAcylation,which was further enhanced by HBV infection.The colony-forming assay demonstrated that the number of cell clones was increased in the AdDHX9 group(386.667±15.630)compared with the AdGFP control group(142.667±7.572,P<0.001).Moreover,cell growth curves demonstrated that the overall cell growth rate was en-hanced in the AdDHX9 group(22.860±0.770)compared with the AdGFP control group(13.670±0.517,P<0.001).Conclusion:HBV infection promotes DHX9 O-GlcNAcylation,which enhances the proliferation of HBV-associated hepatoma cells.
3.Study of a deep learning-based artificial intelligence model for automatic measurement and classification of cystocele
Ting XIAO ; Xiduo LU ; Yunqing CAO ; Zhuoru LUO ; Siyun DU ; Yide QIU ; Chaojiong ZHEN ; Yinghong WEN ; Dong NI ; Weijun HUANG
Chinese Journal of Ultrasonography 2025;34(4):334-339
Objective:To explore the clinical application value of convolutional neural network(CNN)based on deep learning in the automatic measurement of dynamic pelvic floor ultrasound video parameters and the diagnosis and classification of cystocele.Methods:A retrospective analysis was conducted on dynamic pelvic floor ultrasound videos from 398 postpartum women who underwent examinations at the First People's Hospital of Foshan between June 2020 and June 2022. The lowest point of the posterior bladder wall(PWB),urethral rotation angle(URA),and retrovesical angle(RVA)were manually measured by a senior radiologist(R1)and a junior radiologist(R2),and cystocele was classified according to the Green standard. The CNN model was employed to automatically extract the above parameters and to diagnose and classify cystocele. Using R1 measurements as a reference,intraclass correlation coefficient(ICC)was used to evaluate the consistency between the CNN model and R1,as well as between R2 and R1. The Kappa value was used to assess the agreement between the CNN model,R2,and R1 in the diagnosis and classification of cystocele. Additionally,the time consumption of the three measurement methods was compared.Results:The CNN model showed good consistency with R1 in measuring PWB and URA(ICC = 0.983,0.894),while its consistency in measuring RVA was moderate(ICC = 0.614). The ICC between R2 and R1 in measuring PWB,URA,and RVA was 0.979,0.815,and 0.627,respectively. In the measurement of PWB and URA,the consistency between the CNN model and R1 was superior to that between R2 and R1. For cystocele diagnosis,the Kappa value between the CNN model and R1 was 0.924,which was higher than that between R2 and R1(0.904). In cystocele classification,the Kappa value between the CNN model and R1 was 0.503,also higher than that between R2 and R1(0.426). The CNN model processed a single video in 2.5(0.6)s,significantly faster than R1[59.9(16.9)s]and R2[56.8(11.2)s](all P < 0.001). Conclusions:The CNN model demonstrates high accuracy and efficiency in the measurement,diagnosis,and classification of cystocele,outperforming a junior radiologist and showing potential for clinical application.
4.Application of proximal femoral reconstruction osteotomy in hip revision arthroplasty
Min CHEN ; Guoyuan LI ; Zhengliang LUO ; Xiaoqi ZHANG ; Zhe NI ; Xiaofeng JI ; Xifu SHANG
Chinese Journal of Orthopaedic Trauma 2025;27(6):492-498
Objective:To evaluate the clinical efficacy of proximal femoral reconstruction osteotomy (PFRO) in hip revision arthroplasty.Methods:A retrospective analysis was conducted of the 92 patients (93 hips) who had undergone PFRO in hip revision arthroplasty at Department of Orthopedics, The First Affiliated Hospital, University of Science and Technology of China from January 2019 to December 2023. The cohort included 50 males (51 hips) and 42 females (42 hips), with an age of (64.5±11.7) years and a body mass index of (23.7±2.9) kg/m 2. Surgical procedures were performed under general anesthesia via a posterolateral approach. Biologic prostheses were used in femoral reconstruction, and PFRO fragments repositioned and fixed using cerclage wires. The data collected were operative time, intraoperative blood loss, length of osteotomy fragments, healing at the osteotomy site, intraoperative and follow-up complications, as well as Harris hip score (HHS) and leg length discrepancy (LLD) at the last follow-up. Results:For this cohort, operative time was (174.9±45.6) minutes, intraoperative blood loss (594.6±206.6) mL, and length of osteotomy fragments (12.3±2.3) mm. The 92 patients were followed up for (35.8±12.3) months. For them, HHS improved from preoperative (38.3±8.5) points to (80.5±12.8) points at the last follow-up, and LLD decreased from preoperative (21.2±13.0) mm to 2.0(0.0, 5.0) mm at the last follow-up, showing significant differences ( P<0.05). The osteotomy sites healed in 89 cases (90 hips), with a displacement of the greater trochanter <5 mm; 3 cases (3 hips) experienced nonunion with wire loosening and a displacement of the greater trochanter >10 mm. The osteotomy fragment of the greater trochanter got fractured in 2 patients (2 hips) and a fracture of the medial cortex of the proximal femur occurred in 11 patients (11 hips), but follow-ups observed healing of all the fractures. One patient (1 hip) developed postoperative posterior dislocation of the hip which was treated conservatively. One patient (1 hip) developed postoperative periprosthetic infection which did not recur after twice of debridement followed by prosthetic revision of the proximal femoral tumor. Conclusion:In hip revision arthroplasty, as PFRO demonstrates a low incidence of fragment fractures of the greater trochanter and a high rate of healing at the osteotomy site, its short-term clinical outcomes are satisfactory.
5.Ammonium tetrathiomolybdate, a copper chelating agent, alleviates collagen-induced rheumatoid arthritis in dilution brown non-Agoutia/1 mice
Zhe LI ; Huili DENG ; Xuchang ZHOU ; Xier CHEN ; Zhangyu LIN ; Xiaofei LUO ; Xuan WEI ; Guoxin NI
Chinese Journal of Orthopaedic Trauma 2025;27(7):620-628
Objective:To investigate the therapeutic effects of the copper chelator ammonium tetrathiomolybdate (TTM) on rheumatoid arthritis (RA) in a mouse model.Methods:Twenty-four male dilution brown non-Agoutia/1 mice were randomly divided into 4 groups: a blank control group (Ctrl group, n=6), a collagen-induced arthritis (CIA) + phosphate buffer saline (PBS) treatment group (PBS group, n=6), a CIA+TTM treatment group (TTM group, n=6), and a CIA+Elesclomol treatment group (Eles group, n=6). Eles, a copper ion carrier, served as a control for administration of TTM, a copper ion chelator. One week after treatment, the swelling of mouse paw was observed, and the clinical scoring of the arthritis in mice was evaluated once a week. Paw mechanical pain detection was performed and photographs were taken to observe the severity of paw swelling before the mice were sacrificed. Catwalk gait analysis system was used to evaluate the gait changes in mice. HE and saffron O solid green staining were used to evaluate pathomorphologic changes in the mice knee joints and paws. Immunostaining techniques were used to detect the protein expression of MMP3, CD31, and VEGF in the mice paws. Luminex technology was used to detect alterations in the serum inflammatory factors. Results:Compared with the Ctrl group, in the PBS and Eles groups, the joints were red, swollen and deformed; the arthritis clinical scores were significantly higher; the bone destruction, synovial hyperplasia and inflammatory cell infiltration and pathological changes in the joint tissues were obvious; the expression levels of inflammatory factors, such as serum MCP-1, IL-1 β, IL-9, and IFN- γ, were significantly higher while the expression level of IL-10 was significantly lower. Simultaneously, the expression of CD31 and VEGF factors was significantly enhanced. Compared with the PBS group, in the TTM group, the joint swelling and deformation were significantly improved, the arthritis clinical score was reduced, and the joint bone destruction, inflammatory cell infiltration and synovial hyperplasia were alleviated, and the levels of serum MCP-1, IL-1 β, IL-9 and IFN- γ were significantly decreased while the level of anti-inflammatory factor IL-10 was increased. There was no significant difference in the expression of MMP-3, CD31 or VEGF factors between the CTRL group and the TTM group. Conclusion:TTM can block synovial inflammation, angiogenesis, and bone destruction multiple times by simultaneously targeting multiple inflammatory factors, VEGF factors, and bone destruction mediators, thereby alleviating the pathological damage to the joint tissues induced by CIA in RA mice.
6.Application of brain-computer interface in the rehabilitation after spinal cord injury: a review
Xiangxin LYU ; Hong ZHOU ; Zineng YAN ; Changmao NI ; Jinbo YU ; Rui LUO ; Li HUANG ; Zhewei YE
Chinese Journal of Trauma 2025;41(1):106-110
Spinal cord injury (SCI) is a neurological disorder that occurs after a direct or indirect violent injury to the spinal cord, often resulting in sensory and motor dysfunction below the injury level. Patients with SCI are often paralyzed in bed due to impaired nerve function and there has been no effective treatment for limb paralysis after SCI. As a cutting-edge technology with a multidisciplinary integration of neuroscience, computer science, biological engineering, electronic engineering and psychology, brain-computer interface (BCI) provides a new program for the rehabilitation of SCI patients by changing the traditional brain signal output pathways and realizing the direct connection between the brain and external devices. In order to further understand the application of BCI in SCI rehabilitation, the authors reviewed the classification, basic principles of BCI and the research progress of the application of BCI in SCI rehabilitation, which may provide references for the clinical transformation of BCI.
7.The effect of exercise on knee function after anterior cruciate ligament reconstruction
Sijia LUO ; Jianqiu GONG ; Lei WANG ; Xuanyuan LU ; Peiqi NI ; Yutao YING ; Xian SHAO
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(6):530-533
Objective:To observe the effect of rehabilitative exercise on knee function after anterior cruciate ligament (ACL) reconstruction.Methods:Fifty-eight patients with a reconstructed ACL were divided at random into a control group of 28 and an experimental group of 30. In addition to conventional basic treatment, the control group received routine orthopedic rehabilitation training, while the experimental group underwent exercise-based rehabilitation training 6 days a week for 6 weeks. Before and after the treatment, the efficacy in both groups was evaluated using Lysholm knee scoring (LKSS), numerical pain scoring (NRS), maximum knee flexion angle, and a thigh muscle atrophy index.Results:Both groups had significantly higher LKSS scores, lower NRS scores, larger maximum knee flexion angles, and increased thigh muscle atrophy indices, on average, after their treatments. Compared with the control group, the experimental group tended to have significantly higher LKSS scores, larger maximum knee flexion angles, and lower thigh muscle atrophy indices after the treatment. There was, however, no significant difference between the groups in their average NRS scores.Conclusions:Exercise-based rehabilitation training significantly improves the knee function of patients after ACL reconstruction, and its efficacy is superior to conventional orthopedic rehabilitation training.
8.Application of health big data in hospital-based cancer screening study
Chenran WANG ; Zeming GUO ; Xiaoyue SHI ; Yadi ZHENG ; Zilin LUO ; Jiaxin XIE ; Xiaolu CHEN ; Jibin LI ; Yongjie XU ; Wei CAO ; Fei WANG ; Xuesi DONG ; Ni LI ; Jie HE
Chinese Journal of Epidemiology 2025;46(7):1297-1303
This paper focuses on the application of health big data in cancer screening. Firstly, the sources and characteristics of health big data are introduced, then the commonly used epidemiological designs and analytical techniques in hospital-based cancer screening studies are summarized and the application scenarios of such studies are described. Finally, the challenges and future development in the application of health big data are analyzed to provide reference for the future studies.
9.A multicenter clinical study on intramedullary vancomycin injection for preventing periprosthetic joint infection in total knee arthroplasty
Te LIU ; Jun FU ; Shiguang LAI ; Zhuo ZHANG ; Chi XU ; Lei GENG ; Yang LUO ; Peng REN ; Xin ZHI ; Quanbo JI ; Heng ZHANG ; Runkai ZHAO ; Haichao REN ; Ye TAO ; Qingyuan ZHENG ; Zeyu FENG ; Jianfeng YANG ; Yiming WANG ; Pengcheng LI ; Shuai LIU ; Wei CHAI ; Xiang LI ; Huiwu LI ; Xiaogang ZHANG ; Baochao JI ; Xianzhe LIU ; Xinzhan MAO ; Jianbing MA ; Xiangxiang SUN ; Jiying CHEN ; Yonggang ZHOU ; Jinliang WANG ; Weijun WANG ; Guoqiang ZHANG ; Ming NI
Chinese Journal of Orthopaedics 2025;45(12):803-811
Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.
10.Application Value of 18F-FDG PET/CT Metabolic Parameters in Prognosis of Nasopharyngeal Carcinoma
Shanshan HE ; Nana LUO ; Xiaoyan HU ; Lei LI ; Yin NI ; Dasheng QIU
Cancer Research on Prevention and Treatment 2025;52(9):741-746
Objective To investigate the value of 18F-FDG PET/CT metabolic parameters in the prognostic assessment of nasopharyngeal cancer patients. Methods The clinical data and PET/CT metabolic parameters of 185 nasopharyngeal cancer patients were retrospectively analyzed. The collected parameters were SUVmax, MTV, TLG, total metabolic tumor volume (TMTV) and whole-body total lesion glycolysis (WTLG). The ROC curve was used to determine the optimal cut-off values of PET/CT metabolic parameters. Univariate and multivariate Cox regression models were used to screen the independent prognostic factors. Kaplan–Meier curves were used to analyze the survival differences. Results The results of univariate Cox regression analysis showed that age, pathologic type, WTLG, TMTV, MTV, and TLG were closely associated with OS and PFS; and SUVmax was associated with PFS (P<0.05). Multivariate Cox regression analysis results showed that age, TMTV, and WTLG were the independent prognostic factors for OS and PFS (P<0.05). The combination of WTLG with T/N staging (AUC=0.781 and 0.781) and TMTV with T/N staging (AUC=0.800 and 0.790) yielded greater predictive accuracy than that of WTLG and TMTV alone (AUC=0.724 and 0.719) or T/N staging (AUC=0.593 and 0.575). Conclusion TMTV and WTLG are important prognostic predictors of nasopharyngeal carcinoma. TLG and MTV of primary lesions are prognostic factors for patients’ PFS and OS. SUVmax has limited prognostic value. Systemic metabolic indexes (TMTV and WTLG), when combined with T/N staging, can optimize prognostic stratification.

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