1.Development of a machine learning-based preoperative prediction model for spread through air spaces in early-stage lung adenocarcinoma
Kai CHU ; Xinrong XU ; Zhenyu LIU ; Qinglin REN ; Wenbo HE ; Minlu HU ; Xiaolin WANG ; Yusheng SHU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(08):1212-1221
Objective To develop and validate a machine learning model based on preoperative clinical characteristics, laboratory indices, and radiological features for the non-invasive prediction of spread through air spaces (STAS) in patients with early-stage lung adenocarcinoma. Methods Preoperative data from patients with early-stage lung adenocarcinoma who underwent surgical resection at Northern Jiangsu People's Hospital between January 2020 and August 2025 were retrospectively collected. The data included clinical characteristics, laboratory indices, and radiological features. Patients were divided into a STAS-positive and a STAS-negative group based on postoperative pathological findings. The dataset was randomly split into a training set and a testing set at a 7 : 3 ratio. Feature variables were selected using the maximum relevance and minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator (LASSO) regression. Five machine learning models were constructed: logistic regression (LR), random forest (RF), support vector machine (SVM), light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). The shapley additive explanations (SHAP) method was employed to interpret the optimal prediction model. Results A total of 377 patients were included, comprising 177 (46.9%) males and 200 (53.1%) females, with a mean age of (63.31±9.73) years. There were 261 patients in the training set and 116 patients in the testing set. In the training set, statistically significant differences were observed between the STAS-positive group (n=130) and STAS-negative group (n=131) across multiple features, including age, sex, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), clinical T stage, and maximum solid component diameter (P<0.05). A final set of 10 feature variables was selected by combining mRMR and LASSO regression, and five machine learning models (LR, RF, SVM, LightGBM, XGBoost) were developed. The XGBoost model demonstrated optimal performance in both the training and testing sets, achieving AUCs of 0.947 [95%CI (0.920, 0.975)] and 0.943 [95%CI (0.894, 0.993)], respectively. DCA indicated that the XGBoost model provided a high net clinical benefit across a wide range of threshold probabilities. SHAP analysis revealed that the vessel convergence sign, clinical T stage, age, consolidation-to-tumor ratio (CTR), and MLR were the features with the highest contributions to STAS prediction. Conclusion The XGBoost model effectively predicts preoperative STAS status in early-stage lung adenocarcinoma, exhibiting excellent discriminative performance and good clinical interpretability. Key predictors such as the vessel convergence sign, clinical T stage, age and CTR provide a crucial reference for preoperative risk assessment and the individualized selection of surgical strategies, ultimately benefiting patients.
2.Three-dimensional classification and clinical treatment of posterior cruciate ligament tibial avulsion fracture based on CT.
Guang-Kai REN ; Yu-Hang TIAN ; Ming-Yu CUI ; Bao-Ming YUAN ; Yan-Bing WANG ; Chuan-Gang PENG ; Ming LI ; Dan-Kai WU
China Journal of Orthopaedics and Traumatology 2025;38(4):389-395
OBJECTIVE:
A new three-dimensional(3D) classification of posterior cruciate ligament (PCL) tibial avulsion fracture based on computed tomography(CT) features was established and the significance in clinical treatment was explored in this study.
METHODS:
From May 2013 to November 2023, 43 cases of PCL tibial avulsion fracture in the Second Hospital of Jilin University were analyzed retrospectively, including 29 males and 14 females, aged (34.3±8.5) years. According to traditional Meyers and McKeever classification, 3 cases were typeⅠ;2 cases of typeⅡ;38 cases were type Ⅲ. Based on the characteristics of CT images, 43 patients were given specific treatment strategies and followed up to evaluate the curative effect. According to the degree of fracture displacement, involved range and the integrity of fracture block demonstrated by CT images, the new three-dimensional classification of PCL avulsion fracture was established. Kappa coefficient was used for consistency test.
RESULTS:
A new 3D classification of PCL tibial avulsion fracture was established. TypeⅠwas the non-displaced fracture (displacement degree ≤3 mm), in which typeⅠa was the avulsion range limited in the posterior intercondylar fossa, and Ib was the avulsion range beyond the posterior intercondylar fossa. TypeⅡrepresented the displaced fracture in the posterior intercondylar fossa (avulsion limited to the posterior intercondylar fossa and fracture displacement>3 mm), in which typeⅡa represented a slight displacement with a intact broken block and the posterior elevation of the avulsion (hinge mechanism), typeⅡb represented the complete separation of fracture ends with a intact fracture block, and typeⅡc was the comminuted fracture. Type Ⅲ was the displaced fracture beyond the posterior intercondylar fossa (avulsion involving the articular surface of the tibial plateau or the intercondylar ridge and the degree of displacement > 3 mm), among which type Ⅲa was the simple fracture with intact broken block, type Ⅲb represented the comminuted fracture, and type Ⅲc was the complex fracture with tibial plateau fracture. According to this new 3D classification, 43 patients were classified as type Ia in 2 cases and typeⅠb in 1 case;typeⅡa in 2 cases, typeⅡb in 15 cases and typeⅡc in 7 cases;type Ⅲa in 2 cases, type Ⅲb in 5 cases and type Ⅲc in 9 cases. All the 43 cases in this study achieved bone union. At the last follow-up, according to the hospital for special surgery knee score(HSS)evaluation system for the knee joint function, 27 cases were excellent, 11 cases were good, 5 cases were fair. The average Kappa value of inter-observer reliability in the first stage was 0.793, and the second stage was 0.855. The average Kappa value of the whole stage was 0.839, indicating high level of consistency. The average Kappa value of intra-observer reliability was 0.893, indicating high level of consistency.
CONCLUSION
The 3D classification of PCL tibial avulsion fracture is intuitive, demonstrating a high level of reliability. It has a certain guiding significance for the selection of clinical treatment methods, and it is suggested to be promoted and applied as a new classification system in clinical practice.
Humans
;
Male
;
Female
;
Posterior Cruciate Ligament/surgery*
;
Adult
;
Tibial Fractures/classification*
;
Tomography, X-Ray Computed
;
Middle Aged
;
Retrospective Studies
;
Fractures, Avulsion/classification*
;
Imaging, Three-Dimensional
;
Young Adult
3.Clinical study on the treatment of traumatic osteomyelitis of the upper tibia by membrane-induced technique combined with gastrocnemius muscle flap transposition.
Yi-Yang LIU ; Yi-Hang LU ; Qiong-Lin CHEN ; Bing-Yuan LIN ; Hai-Yong REN ; Kai HUANG ; Yang ZHANG ; Qiao-Feng GUO
China Journal of Orthopaedics and Traumatology 2025;38(9):937-944
OBJECTIVE:
To explore clinical efficacy of membrane-induced technique combined with gastrocnemius muscle flap transposition in treating traumatic osteomyelitis of the upper tibia.
METHODS:
A retrospective analysis was conducted on 7 patients with traumatic osteomyelitis of the upper tibia who were treated with membrane-induced technique combined with gastrocnemius muscle flap transposition from January 2022 to December 2023. Among them, there were 4 males and 3 females; aged from 29 to 57 years old; 4 patients were treated after open fracture, 2 patients were treated after closed fracture, and 1 patient was treated after scalding; the courses of disease ranges from 2 weeks to 8 years; sinus tracts were present in all patients, and the lesion range of the tibia ranged from 5 to 9 cm. The results of deep tissue bacterial culture showed that 2 patients were negative, 3 patients were staphylococcus aureus, 1 patient was methicillin-resistant staphylococcus aureus, and 1 patient was pseudomonas aeruginosa and 1 patient was klebsiella pneumoniae. After debridement, the range of bone defect ranged from 8 to 12 cm, and the cortical defect accounted for approximately 30% of the circumference. The area of soft tissue defect ranged from 8.0 cm×2.0 cm to 10.0 cm×6.0 cm. At the first stage, vancomycin-loaded/meropenem/gentamicin-loaded bone cement was implanted. The gastrocnemius muscle flap was repositioned to cover the wound surface and free skin grafting was performed. After an interval of 7 to 10 weeks, the stageⅡsurgery was performed to remove bone cement. Autologous iliac bone mixed with vancomycin/gentamicin and calcium sulfate artificial bone was transplanted, and the wound was sutured. One patient retained the original internal plants, one patient removed the internal plants and replaced them with steel plate external fixation, one patient replaced the internal plants and added steel plate external fixation, and three patients were simply fixed with steel plate external fixation. One year after operation, the recovery of knee joint and ankle joint functions was evaluated by using Hospital for Special Surgery (HSS) knee joint score and Kofoed ankle joint function score respectively.
RESULTS:
All patients had their wounds closed simultaneously with bone cement implantation and healed well. All patients were followed up for 12 to 17 months after operation, and satisfactory bone healing was achieved at 6 months after stageⅡsurgery. Twelve months after operation, all patients had good bone healing without obvious limping was observed when walking. At 12 months after operation HSS knee joint score ranged from 93 to 100 points, and Kofoed ankle function score ranged from 96 to 100 points.
CONCLUSION
For traumatic osteomyelitis of the upper tibia, a staged treatment plan combining membrane-induced technique and gastrocnemius flap transposition on the basis of thorough debridement could safely cover the wound surface, effectively control bone infection and achieve satisfactory bone healing, without adverse effects on limb function.
Humans
;
Male
;
Female
;
Middle Aged
;
Osteomyelitis/surgery*
;
Adult
;
Surgical Flaps
;
Retrospective Studies
;
Tibia/injuries*
;
Muscle, Skeletal/surgery*
4.A novel glycolysis-related prognostic risk model for colorectal cancer patients based on single-cell and bulk transcriptomic data.
Kai YAO ; Jingyi XIA ; Shuo ZHANG ; Yun SUN ; Junjie MA ; Bo ZHU ; Li REN ; Congli ZHANG
Chinese Journal of Cellular and Molecular Immunology 2025;41(2):105-115
Objective To explore the prognostic value of glycolysis-related genes in colorectal cancer (CRC) patients and formulate a novel glycolysis-related prognostic risk model. Methods Single-cell and bulk transcriptomic data of CRC patients, along with clinical information, were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Glycolysis scores for each sample were calculated using single-sample Gene Set Enrichment Analysis (ssGSEA). Kaplan-Meier survival curves were generated to analyze the relationship between glycolysis scores and overall survival. Novel glycolysis-related subgroups were defined among the cell type with the highest glycolysis scores. Gene enrichment analysis, metabolic activity assessment, and univariate Cox regression were performed to explore the biological functions and prognostic impact of these subgroups. A prognostic risk model was built and validated based on genes significantly affecting the prognosis. Gene Set Enrichment Analysis (GSEA) was conducted to explore differences in biological processes between high- and low-risk groups. Differences in immune microenvironment and drug sensitivity between these groups were assessed using R packages. Potential targeted agents for prognostic risk genes were predicted using the Enrichr database. Results Tumor tissues showed significantly higher glycolysis scores than normal tissues, which was associated with a poor prognosis in CRC patients. The highest glycolysis score was observed in epithelial cells, within which we defined eight novel glycolysis-related cell subpopulations. Specifically, the P4HA1+ epithelial cell subpopulation was associated with a poor prognosis. Based on signature genes of this subpopulation, a six-gene prognostic risk model was formulated. GSEA revealed significant biological differences between high- and low-risk groups. Immune microenvironment analysis demonstrated that the high-risk group had increased infiltration of macrophages and tumor-associated fibroblasts, along with evident immune exclusion and suppression, while the low-risk group exhibited higher levels of B cell and T cell infiltration. Drug sensitivity analysis indicated that high-risk patients were more sensitive to Abiraterone, while low-risk patients responded to Cisplatin. Additionally, Valproic acid was predicted as a potential targeted agent. Conclusion High glycolytic activity is associated with a poor prognosis in CRC patients. The novel glycolysis-related prognostic risk model formulated in this study offers significant potential for enhancing the diagnosis and treatment of CRC.
Humans
;
Colorectal Neoplasms/pathology*
;
Glycolysis/genetics*
;
Prognosis
;
Transcriptome
;
Tumor Microenvironment/genetics*
;
Gene Expression Profiling
;
Single-Cell Analysis
;
Gene Expression Regulation, Neoplastic
;
Male
;
Female
;
Kaplan-Meier Estimate
5.Tanshinone II A Facilitates Chemosensitivity of Osteosarcoma Cells to Cisplatin via Activation of p38 MAPK Pathway.
Da-Ming XIE ; Zhi-Yun LI ; Bing-Kai REN ; Rui GONG ; Dong YANG ; Sheng HUANG
Chinese journal of integrative medicine 2025;31(4):326-335
OBJECTIVE:
To examine the mechanism of action of tanshinone II A (Tan II A) in promoting chemosensitization of osteosarcoma cells to cisplatin (DDP).
METHODS:
The effects of different concentrations of Tan II A (0-80 µ mol/L) and DDP (0-2 µ mol/L) on the proliferation of osteosarcoma cell lines (U2R, U2OS, 143B, and HOS) at different times were examined using the cell counting kit-8 and colony formation assays. Migration and invasion of U2R and U2OS cells were detected after 24 h treatment with 30 µ mol/L Tan II A, 0.5 µ mol/L DDP alone, and a combination of 10 µ mol/L Tan II A and 0.25 µ mol/L DDP using the transwell assay. After 48 h of treatment of U2R and U2OS cells with predetermined concentrations of each group of drugs, the cell cycle was analyzed using a cell cycle detection kit and flow cytometry. After 48 h treatment, apoptosis of U2R and U2OS cells was detected using annexin V-FITC apoptosis detection kit and flow cytometry. U2R cells were inoculated into the unilateral axilla of nude mice and then the mice were randomly divided into 4 groups of 6 nude mice each. The 4 groups were treated with equal volume of Tan II A (15 mg/kg), DDP (3 mg/kg), Tan II A (7.5 mg/kg) + DDP (1.5 mg/kg), and normal saline, respectively. The body weight of the nude mice was weighed, and the tumor volume and weight were measured. Cell-related gene and signaling pathway expression were detected by RNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway analysis. p38 MAPK signaling pathway proteins and apoptotic protein expressions were detected by Western blot.
RESULTS:
In vitro studies have shown that Tan II A, DDP and the combination of Tan II A and DDP inhibit the proliferation, migration and invasion of osteosarcoma cells. The inhibitory effect was more pronounced in the Tan II A and DDP combined treatment group (P<0.05 or P<0.01). Osteosarcoma cells underwent significantly cell-cycle arrest and cell apoptosis by Tan II A-DDP combination treatment (P<0.05 or P<0.01). In vivo studies demonstrated that the Tan II A-DD combination treatment group significantly inhibited tumor growth compared to the Tan II A and DDP single drug group (P<0.01). Additionally, we found that the combination of Tan II A and DDP treatment enhanced the p38 MAPK signaling pathway. Western blot assays showed higher p-p38, cleaved caspase-3, and Bax and lower caspase-3, and Bcl-2 expressions with the combination of Tan II A and DDP treatment compared to the single drug treatment (P<0.01).
CONCLUSION
Tan II A synergizes with DDP by activating the p38/MAPK pathway to upregulate cleaved caspase-3 and Bax pro-apoptotic gene expressions, and downregulate caspase-3 and Bcl-2 inhibitory apoptotic gene expressions, thereby enhancing the chemosensitivity of osteosarcoma cells to DDP.
Abietanes/therapeutic use*
;
Osteosarcoma/enzymology*
;
Cisplatin/therapeutic use*
;
Humans
;
Cell Line, Tumor
;
Animals
;
Apoptosis/drug effects*
;
Mice, Nude
;
Cell Proliferation/drug effects*
;
Cell Movement/drug effects*
;
p38 Mitogen-Activated Protein Kinases/metabolism*
;
MAP Kinase Signaling System/drug effects*
;
Bone Neoplasms/enzymology*
;
Cell Cycle/drug effects*
;
Xenograft Model Antitumor Assays
;
Mice
;
Drug Resistance, Neoplasm/drug effects*
;
Neoplasm Invasiveness
;
Mice, Inbred BALB C
6.Expert consensus on prognostic evaluation of cochlear implantation in hereditary hearing loss.
Xinyu SHI ; Xianbao CAO ; Renjie CHAI ; Suijun CHEN ; Juan FENG ; Ningyu FENG ; Xia GAO ; Lulu GUO ; Yuhe LIU ; Ling LU ; Lingyun MEI ; Xiaoyun QIAN ; Dongdong REN ; Haibo SHI ; Duoduo TAO ; Qin WANG ; Zhaoyan WANG ; Shuo WANG ; Wei WANG ; Ming XIA ; Hao XIONG ; Baicheng XU ; Kai XU ; Lei XU ; Hua YANG ; Jun YANG ; Pingli YANG ; Wei YUAN ; Dingjun ZHA ; Chunming ZHANG ; Hongzheng ZHANG ; Juan ZHANG ; Tianhong ZHANG ; Wenqi ZUO ; Wenyan LI ; Yongyi YUAN ; Jie ZHANG ; Yu ZHAO ; Fang ZHENG ; Yu SUN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(9):798-808
Hearing loss is the most prevalent disabling disease. Cochlear implantation(CI) serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system(Favorable, Marginal, Poor). The consensus focuses on common hereditary non-syndromic hearing loss(such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1) and syndromic hereditary hearing loss(such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome), which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans
;
Cochlear Implantation
;
Prognosis
;
Hearing Loss/surgery*
;
Consensus
;
Connexin 26
;
Mutation
;
Sulfate Transporters
;
Connexins/genetics*
7.Modulation of cardiac inflammation by Qifu Yixin Granules in rats with heart failure via TLR4/MyD88/NF-κB signaling pathway
Qian-rong LI ; Xiao-dong ZHI ; Bing JIANG ; Chun-ling WANG ; Chun-zhen REN ; Xin-ke ZHAO ; Kai LIU ; Ying-dong LI
Chinese Traditional Patent Medicine 2025;47(8):2535-2541
AIM To investigate the effects of Qifu Yixin Granules on cardiac inflammation in a rat model of heart failure.METHODS The rats were induced into chronic heart failure(CHF)models by 6-week intraperitoneal injection of doxorubicin followed by the random assignment of the successful rat models into the model group,the captopril group(22.5 mg/kg),and the low-dose,medium-dose,and high-dose Qifu Yixin Granules groups(2.84,5.67,11.34 g/kg),in contrast to the normal rats of the blank group.The rats had their body weight monitored;their cardiac function assessed by echocardiography;their serum levels of NT-proBNP,TNF-α,IL-6,IL-1 and CRP measured by ELISA;their cardiac morphological alterations observed by HE and Masson staining;their cardiac protein expressions of TLR4,MyD88 and NF-κB detected by immunohistochemistry and Western blot;and their cardiac mRNA expressions of TLR4,MyD88 and NF-κB measured by RT-qPCR.RESULTS Compared to the blank group,the model group exhibited significantly reduced body weight,LVEF and LVFS(P<0.01),alongside significantly elevated LVEDD,LVESD,and serum concentrations of NT-proBNP,TNF-α,IL-6,IL-1 and CRP(P<0.01).Additionally,the model group displayed greater myocardial inflammatory cell aggregation,increased collagen deposition(P<0.01);and upregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P<0.01).Compared to the model group,the groups intervened with captopril or medium/high dose Qifu Yixin Granules demonstrated significantly increased body weight,LVEF and LVFS(P<0.05,P<0.01);significantly reduced LVEDD,LVESD,and serum levels of the aforementioned indicators(P<0.05,P<0.01);mitigated inflammation and collagen deposition(P<0.05,P<0.01);and downregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P<0.05,P<0.01).CONCLUSION Qifu Yixin Granules attenuate cardiac inflammation and improve cardiac function in doxorubicin-induced CHF rats;this therapeutic effect is mediated by inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway.
8.Efficacy and mechanism of botulinum toxin type A combined with static progressive stretching in the treatment of traumatic knee stiffness in rats
Ke CHEN ; Xin ZHANG ; Kai REN ; Yingying LIAO ; Xin HE ; Xiaoju LI
Chinese Journal of Trauma 2025;41(2):201-211
Objective:To investigate the efficacy and mechanism of botulinum toxin type A (BTX-A) combined with static progressive stretching (SPS) in the treatment of traumatic knee stiffness in rats.Methods:Forty healthy male SD rats aged 8 weeks and weighing 220-300 g, were randomly divided into blank control group ( n=8) and model groups ( n=28) (including injury group, BTX-A group, SPS group and BTX-A+SPS group, with 7 in each group). Hlidebrand′s method was used to construct a traumatic knee stiffness model, with the following main steps: destruction of the joint capsule, Kirschner wire fixation, joint drilling, and removal of the internal fixation at 4 weeks. The blank control group did not receive any treatment and could move freely in the cage. The injury group moved freely after successful modeling. On the day of internal fixation removal, BTX-A was injected into the joint cavity in group BTX-A, SPS treatment was started in the SPS group, BTX-A was injected into the joint cavity and SPS treatment was started in the BTX-A+SPS group. The treatments lasted 16 days. The range of motion (ROM) and joint stiffness were measured before treatment and at 16 days after treatment. At 16 days after treatment, knee joint tissue was collected and the rats were sacrificed, and the articular capsule fibrous tissue proliferation was observed by HE and Masson staining. The expression levels of phosphorylated (p)-Smad2, Smad2, p-Smad3, Smad3, Smad4, transforming growth factor-β1 (TGF-β1), collagen type I, collagen type III, and α-smooth actin (α-SMA) were determined by Western blot. The ratio of phosphorylated protein to total protein was calculated to reflect the phosphorylation level. Results:(1) ROM: Before treatment, the ROM in the blank control group was significantly higher than that in the other groups ( P<0.05), with no significant difference in ROM among the other groups ( P>0.05). At 16 days after treatment, ROM in the injury group, BTX-A group, SPS group, and BTX-A+SPS group was lower than that in the blank control group ( P<0.05), among which ROM in the BTX-A+SPS group was significantly higher than that in the injury group, BTX-A group, and SPS group ( P<0.05). At 16 days after treatment, there was no significant difference in ROM before and after treatment in the blank control group ( P>0.05), and ROM in the other groups was significantly increased compared with that before treatment ( P<0.01). (2) Joint stiffness: At 16 days after treatment, the joint stiffness levels in the injury group, the BTX-A group, and the SPS group were (0.95±0.24)N·cm/°, (0.86±0.22)N·cm/°, and (0.65±0.09)N·cm/° respectively, which were significantly lower than (0.36±0.03)N·cm/° in the blank control group ( P<0.05). The joint stiffness level of the BTX-A+SPS group was (0.49±0.04)N·cm/°, which was not significantly different from that in the blank control group ( P>0.05), but was significantly lower than those in the injury group, BTX-A group, and SPS group ( P<0.05). (3) Fibrous tissue proliferation: at 16 days after treatment, the joint capsular structure in the blank control group was complete and clear, the fibers were arranged in order, and there was no obvious fibrous tissue proliferation. The pathological changes in the injury group were the most serious, with a large number of synovial fibrous tissue proliferation, significantly increased blood vessels in the tissue, and inflammatory cell infiltration. Compared with the SPS group and BTX-A group, the lesions in BTX-A+SPS group were milder, with only slight increase in the number of synovial cells but no obvious vascular proliferation or lymphocytes, and the overall lesions were the least severe. (4) Protein expression: the ratios of p-Smad2/Smad2 in the injury group, BTX-A group and SPS group were 1.552±0.234, 1.328±0.272 and 1.194±0.277 respectively, which were higher than 0.794±0.082 in the blank control group ( P<0.05). The ratio of p-Smad2/Smad2 in the BTX-A+SPS group was 1.013±0.123, which was not significantly different from those in the blank control group, BTX-A group or SPS group ( P>0.05), but was lower than that in the injury group ( P<0.05). At 16 days after treatment, the p-Smad3/Smad3 ratios in the injury group, BTX-A group, SPS group and BTX-A+SPS group were 2.272±0.309, 1.664±0.285, 1.381±0.276 and 1.003±0.060 respectively, which were higher than 0.515±0.051 in the blank control group ( P<0.05). The p-Smad3/Smad3 ratio in the BTX-A+SPS group was significantly lower than those in the injury group, BTX-A group and SPS group ( P<0.05). At 16 days after treatment, the level of Smad4 in the injury group (1.001±0.015) was higher than 0.294±0.076 in the blank control group ( P<0.05). However, there was no significant difference between the BTX-A group (0.664±0.051), SPS group (0.833±0.045), BTX-A+SPS group (0.467±0.068) or the blank control group ( P>0.05). The level of Smad4 in the BTX-A+SPS group was significantly lower than those in the injury group, BTX-A group and SPS group ( P<0.05). At 16 days after treatment, the level of TGF-β1 in the injury group (1.004±0.407) was higher than 0.269±0.122 in the blank control group ( P<0.05), while there was no significant difference between the BTX-A group (0.564±0.194), SPS group (0.422±0.086) and BTX-A+SPS group (0.347±0.161) and the blank control group ( P>0.05). The level of TGF-β1 in the BTX-A+SPS group was significantly lower than those in the injury group, BTX-A group and SPS group ( P<0.05). At 16 days after treatment, the level of type I collagen in the injury group was 0.999±0.170, higher than 0.299±0.139 in the blank control group ( P<0.05), while there was no significant difference between the BTX-A group (0.542±0.278), SPS group (0.561±0.165), and BTX-A+SPS group (0.537±0.045) and the blank control group ( P>0.05). The level of collagen type I in the BTX-A+SPS group was significantly lower than those in the injury group, BTX-A group, and SPS group ( P<0.05). At 16 days after treatment, the level of type III collagen in the injury group was 1.002±0.126, higher than 0.239±0.106 in the blank control group ( P<0.05), while there was no significant difference between the BTX-A group (0.661±0.062), SPS group (0.595±0.062), and BTX-A+SPS group (0.504±0.269) and the blank control group ( P>0.05). The level of collagen type III in the BTX-A+SPS group was significantly lower than those in the injury group, BTX-A group, and SPS group ( P<0.05). At 16 days after treatment, the level of α-SMA in the injury group was 0.998±0.074, higher than 0.130±0.023 in the blank control group ( P<0.05), while there was no significant difference between the BTX-A group (0.358±0.060), SPS group (0.432±0.230), and BTX-A+SPS group (0.293±0.135) and the blank control group ( P>0.05). The level of α-SMA in the BTX-A+SPS group was significantly lower than those in the injury group, BTX-A group and SPS group ( P<0.05). Conclusions:Compared with single treatment, the combination of BTX-A and SPS demonstrates significantly greater efficacy in the treatment of traumatic knee stiffness in rats. This combined approach not only enhances joint mobility and elasticity but also effectively inhibits joint capsule fibrosis. The underlying mechanism may involve the further suppression of TGF-β1 expression in the joint capsule, leading to reduced phosphorylation levels of Smad2 and Smad3. This, in turn, inhibits the binding of Smad2 and Smad3 to the Smad4 receptor, ultimately downregulating the expression of the downstream proteins of the TGF-β/Smad signaling pathway, such as collagen type I, collagen type III and α-SMA.
9.The efficacy of ultrasound-guided genicular nerve block in treating knee osteoarthritis
Fanxiang FENG ; Hai SHEN ; You LI ; Kai REN ; Fulong LIU ; Yicheng XIAO ; Weixia ZHAO ; Xin ZHANG
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(9):834-840
Objective:To document the effectiveness of ultrasound-guided genicular nerve block (GNB) in treating knee osteoarthritis (KOA).Methods:A total of 92 KOA patients were randomly divided into an observation group and a control group with 46 in each. Those in both groups were treated conventionally, including with non-steroidal anti-inflammatory drugs, acupuncture, ultrasound, laser irradiation and manipulation therapy. The observation group additionally underwent ultrasound-guided genicular nerve block treatment, once a week for 2 weeks. Pain scoring on a visual analog scale (VAS), the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and a 6-minute walk test (6MWT) were used to evaluate everyone before and after the treatment, and then 8 weeks later.Results:In the observation group the average VAS rating [(3.54±2.00) at week 2 and (4.13±2.04) at week 8] and the average WOMAC subscale and total scores [(36.91±16.91) at week 8] had improved significantly right after the experiment and 8 weeks later. But in the control group this was true only right after the treatment. The observation group also demonstrated superior improvements in 6MWT distance at week 2 [(434.22±125.19)m] and week 8 [(446.35±126.45)m] compared to both its own baseline and the control group.Conclusions:Ultrasound-guided genicular nerve block is a rapid, precise, effective, and long-lasting intervention for alleviating pain, improving knee function and enhancing walking endurance in KOA patients.
10.Platelet methyltransferase-like protein 4-mediated mitochondrial DNA metabolic disorder exacerbates oral mucosal immunopathology in hypoxia.
Yina ZHU ; Meichen WAN ; Yutong FU ; Junting GU ; Zhaoyang REN ; Yun WANG ; Kehui XU ; Jing LI ; Manjiang XIE ; Kai JIAO ; Franklin TAY ; Lina NIU
International Journal of Oral Science 2025;17(1):49-49
Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood. This condition compromises mucosal barrier integrity particularly in the gut and oral cavity. However, the mechanisms underlying this association remain unclear. This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions. Hypoxia upregulated methyltransferase-like protein 4 (METTL4) expression in platelets, resulting in N6-methyladenine modification of mitochondrial DNA (mtDNA). This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation, leading to cytosolic mtDNA accumulation. Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets. This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis. Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology. Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.
DNA, Mitochondrial/metabolism*
;
Mouth Mucosa/pathology*
;
Hypoxia/immunology*
;
Methyltransferases/metabolism*
;
Blood Platelets/metabolism*
;
Animals
;
Periodontitis/immunology*
;
Humans
;
Platelet Activation
;
Mice

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