Objective Accumulating evidence suggests that diabetes mellitus (DM) aggravates the incidence and severity of ischemia reperfusion injury (IRI). Eriodictyol (EDT), a natural flavonoid with reported nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant and anti-diabetic abilities, has been shown to mitigate IRI in various experimental models. However, its potential effect in diabetic IRI models remains unidentified. This study is aiming to explore the protective role of EDT against hyperglycemia-aggravated IRI and its underlying mechanism. Methods High-fat-high-sugar diets and low-dose streptozotocin (STZ) injection, followed by orthodontic rubber bands (ORBs) wrapping, were utilized to induce the diabetic limb IRI model. C2C12 myoblasts were subjected to hypoxia/reoxygenation (H/R) with or without high-glucose induction. Treatment with intraperitoneal injection of EDT was performed in vivo. Administration with EDT and the Nrf2 inhibitor, ML385, was applied in vitro. Results EDT treatment dose-dependently alleviated skeletal muscle histopathological damage, reduced tissue oxidative injury and apoptosis in IRI-induced diabetic mice. Concurrently, EDT upregulated Nrf2 and its downstream enzymes such as hemeoxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1). In C2C12 cells, EDT activated the Nrf2/HO-1 signaling, which enhanced antioxidant resistance, preserved mitochondrial function, and inhibited apoptosis. Notably, ML385 administration effectively blocked these protective effects, demonstrating their dependence on Nrf2 signaling. Conclusion Eriodictyol mitigates diabetic muscle IRI by means of Nrf2/HO-1 pathway activation, highlighting its potential for managing this severe complication in diabetic patients undergoing orthopedic surgery.

OBJECTIVE:Sepsis-induced cardiomyopathy (SICM) is a frequent and life-threatening complication of sepsis, characterized by acute cardiac dysfunction and high mortality, yet no specific therapy is currently available. Cordycepin (COR), a natural bioactive compound, has been reported to exert anti-inflammatory and cardioprotective effects; however, its role and underlying mechanisms in SICM remain unclear. METHODS:SICM was established in mice by intraperitoneal lipopolysaccharide (LPS) injection or cecal ligation and puncture (CLP). In vitro, HL-1 cells were treated with cytokine mixtures. COR was administered as a pre-treatment in both models. Cardiac function and myocardial injury were evaluated by echocardiography, histopathology, and biochemical assays. Transcriptome sequencing was performed to identify potential pathways, followed by validation using Western blotting and immunofluorescence. Mitochondrial function and cell death were assessed using CCK-8, flow cytometry, JC-1 staining, MitoTracker labeling, and transmission electron microscopy. RESULTS:COR markedly attenuated myocardial injury induced by LPS, CLP, and cytokine stimulation. Compared with the model group, COR improved cardiac function, increased 7-day survival, and reduced myocardial inflammatory responses. Transcriptomic profiling implicated PI3K/Akt/mTOR signaling, and subsequent in vivo and in vitro experiments supported pathway activation by COR. Mechanistically, COR restored mitochondrial homeostasis and alleviated oxidative stress, evidenced by decreased ROS and MDA and increased SOD activity, while enhancing mitochondrial membrane potential and ATP production. COR also suppressed cardiomyocyte apoptosis, reflected by reduced Bax expression and decreased ratios of Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9, along with increased Bcl-2 expression. CONCLUSION:COR mitigates inflammation, oxidative stress, and cardiomyocyte apoptosis in SICM via modulation of the PI3K/Akt/mTOR pathway, thereby attenuating myocardial injury and improving cardiac function. Collectively, these findings indicate that COR may serve as a potential novel therapeutic agent for the management of SICM.

Rapid wound healing with minimal scarring remains a major challenge in regenerative medicine. Here, we present an innovative bilayer wound dressing that integrates a piezoelectric film, [P(VDF-TrFE)]-BTO, with a conductive hydrogel composed of chitosan derivatives (CDMA), modified extracellular matrix (ECMMA), and (CeO₂@PDA) nanoparticles (NPs) to synergistically accelerate wound healing and prevent scar formation. Upon ultrasound stimulation, the upper piezoelectric film generates an electric field (EF). This electric field effectively inhibits fibroblast proliferation and modulates collagen deposition, thereby reducing scar formation. Simultaneously, chitosan derivative (CDMA) within the hydrogel provides essential structural support, superior tissue adhesion, and intrinsic antibacterial activity, while ECMMA supports cell adhesion and regeneration. Additionally, CeO₂@PDA NPs deliver strong antioxidant effects, reducing reactive oxygen species (ROS) and inflammation at the wound site. In vivo studies demonstrated that the synergistic action of piezoelectrically generated EF and bioactive hydrogel significantly accelerated wound closure, improved collagen organization, optimized the collagen I/III ratio, and minimized scarring. This multifunctional bilayer dressing offers an effective strategy for next-generation wound care, integrating physical stimulation and biomaterial-guided regeneration to improve therapeutic outcomes.

Background:Preoperative neoadjuvant chemoradiotherapy (nCRT) is considered to be the standard treatment strategy for locally advanced rectal cancer (LARC); however, the risk of adverse events and postoperative recurrence remains significant. This study aimed to evaluate the non-inferiority of neoadjuvant chemotherapy (nCT) compared with nCRT in patients with LARC and to assess the possibility of eliminating radiotherapy on the basis of guaranteed efficacy. Materials and methods:We searched the PubMed, Embase, and Cochrane Library databases to identify randomized controlled trials (RCTs) comparing the efficacy of nCRT and nCT for LARC. The study protocol was registered with the Prospective Register of Systematic Reviews (PROSPERO). Results:A total of 2706 patients from seven studies were included in the meta-analysis. There was no significant difference in overall survival (OS) or disease-free survival (DFS) between the nCT and nCRT groups. This study demonstrated a lower rate of infection (OR = 0.53, 95% CI = 0.34-0.82; P = 0.005), anastomotic leak (OR = 0.55, 95% CI = 0.34-0.87; P = 0.01), tumor regression grade (TRG) 0-1 (OR = 0.50, 95% CI = 0.36-0.69; P < 0.0001), preventive diverting ileostomy (OR = 0.41, 95% CI = 0.17-1.02; P = 0.05), and leukopenia (OR = 0.50, 95% CI = 0.25-1.01; P = 0.05) in the nCT group. However, there was no significant difference in the other toxic events, such as intestinal obstruction, urinary complications, diarrhea, and surgical or pathological outcomes, such as clinical fistula, sphincter preservation, postoperative mortality (<= 60 d), R0 resection, ypStage 0-I, positive circumferential resection margin (CRM+), or pathological complete response (pCR) between the two groups. Conclusion:This study indicated that OS and DFS were not lower in the nCT group than in the nCRT group. In addition, the nCT group had fewer complications. Preoperative nCT is expected to become a standard treatment option for most patients with stage II-III LARC. It is worth noting that radiotherapy cannot be ignored for some patients who need to ensure the conversion effect of neoadjuvant therapy and strongly request to preserve organ function.

OBJECTIVE:Prolonged or inappropriate mechanical ventilation (MV) can cause ventilator-induced diaphragmatic dysfunction (VIDD), characterized by progressive diaphragmatic atrophy, reduced contractile force and diminished endurance, leading to difficult weaning and increased mortality. The core pathophysiological mechanisms involve mitochondrial dysfunction and aberrant apoptotic pathway activation in diaphragmatic myocytes. Therefore, exploring effective prevention and treatment strategies is crucial. Carnosic acid (CA), a natural compound with significant antioxidant, anti-inflammatory and cytoprotective effects has recently gained interest. However, CA's role in VIDD remains unclear. This study investigates CA's protective effects and potential mechanisms against VIDD, highlighting its promise as a novel therapeutic agent. METHODS:VIDD models in vivo and muscle atrophy models in vitro were established. Mice and C2C12 myotubes were administered CA. Ultrasound, muscle contractility tests, histological examinations, immunofluorescence, western blotting, and biochemical assays were employed to assess oxidative stress levels, atrophy-related proteins alterations and apoptosis levels in the diaphragm following MV. Cell viability assays, flow cytometry and EdU assays were used to measure cell proliferation and apoptosis. JC-1 staining and transmission electron microscopy (TEM) were applied to evaluate mitochondrial morphology and function. RESULTS:CA effectively protected muscle cells both in vivo and in vitro, alleviating MV- and dexamethasone (DXMS)-induced oxidative stress, atrophy, and apoptosis in myocytes. Compared with the model group, CA intervention significantly increased the expression levels of NRf2, p-Nrf2 and HO-1 in both the diaphragms of MV mice and DXMS-treated C2C12 cells. We observed improved mitochondrial morphology and function with decreased expression of ROS, MDA and atrophy-related proteins (MuRF-1/Atrogin-1). Furthermore, CA intervention significantly ameliorated the mitochondrial membrane potential in cardiomyocytes, reduced the expression levels of the pro-apoptotic molecules Bax and the Cleaved-Caspase-3/Caspase-3 and Cleaved-Caspase-9/Caspase-9 ratios, while upregulating the expression level of the anti-apoptotic molecule Bcl-2. CONCLUSION:CA can activate the Nrf2/HO-1 pathway both in vivo and in vitro, mitigate mitochondrial damage and apoptosis in myocytes, attenuate muscle atrophy, and maintain normal physiological function. It can be considered as a potential novel therapeutic agent for the prevention and treatment of VIDD.

A growing amount of epidemiological evidence proposes diabetes mellitus (DM) to be an independent risk factor for osteoarthritis (OA). Sirtuin3 (SIRT3), which is mainly located in mitochondria, belongs to the family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases and is involved in the physiological and pathological processes of cell regulation. The aim of this study was to investigate the effects of SIRT3 on diabetic OA and underlying mechanisms in the prevention of type 2 DM (T2DM)-induced articular cartilage damage. High-fat and high-sugar diets combined with streptozotocin (STZ) injection were used for establishing an experimental T2DM rat model. The destabilization of medial meniscus (DMM) surgery was applied to induce the rat OA model. Primary rat chondrocytes were cultivated with a concentration of gradient glucose. Treatment with intra-articular injection of SIRT3 overexpression lentivirus was achieved in vivo, and intervention with SIRT3 knockdown was performed using siRNA transfection in vitro. High glucose content was found to activate inflammatory response, facilitate apoptosis, downregulate autophagy, and exacerbate mitochondrial dysfunction in a dose-dependent manner in rat chondrocytes, which can be deteriorated by SIRT3 knockdown. In addition, articular cartilage damage was found to be more severe in T2DM-OA rats than in DMM-induced OA rats, which can be mitigated by the intra-articular injection of SIRT3 overexpression lentivirus. Targeting SIRT3 is a potential therapeutic strategy for the alleviation of diabetic OA.

BACKGROUND:The defense response is a type of self-protective response of the body that protects it from damage by pathogenic factors. Although these reactions make important contributions to the occurrence and development of tumors, the role they play in osteosarcoma (OS), particularly in the immune microenvironment, remains unpredictable.METHODS:This study included the clinical information and transcriptomic data of 84 osteosarcoma samples and the microarray data of 12 mesenchymal stem cell samples and 84 osteosarcoma samples. We obtained 129 differentially expressed genes related to the defense response (DRGs) by taking the intersection of differentially expressed genes with genes involved in the defense response pathway, and prognostic genes were screened using univariate Cox regression. Least absolute shrinkage and selection operator (LASSO) penalized Cox regression and multivariate Cox regression were then used to establish a DRG prognostic signature (DGPS) via the stepwise method. DGPS performance was examined using independent prognostic analysis, survival curves, and receiver operating characteristic (ROC) curves. In addition, the molecular and immune mechanisms of adverse prognosis in high-risk populations identified by DGPS were elucidated. The results were well verified by experiments.RESULT:BNIP3, PTGIS, and ZYX were identified as the most important DRGs for OS progression (hazard ratios of 2.044, 1.485, and 0.189, respectively). DGPS demonstrated outstanding performance in the prediction of OS prognosis (area under the curve (AUC) values of 0.842 and 0.787 in the training and test sets, respectively, adj-p < 0.05 in the survival curve). DGPS also performed better than a recent clinical prognostic approach with an AUC value of only 0.674 [metastasis], which was certified in the subsequent experimental results. These three genes regulate several key biological processes, including immune receptor activity and T cell activation, and they also reduce the infiltration of some immune cells, such as B cells, CD8+ T cells, and macrophages. Encouragingly, we found that DGPS was associated with sensitivity to chemotherapeutic drugs including JNK Inhibitor VIII, TGX221, MP470, and SB52334. Finally, we verified the effect of BNIP3 on apoptosis, proliferation, and migration of osteosarcoma cells through experiments.CONCLUSIONS:This study elucidated the role and mechanism of BNIP3, PTGIS, and ZYX in OS progression and was well verified by the experimental results, enabling reliable prognostic means and treatment strategies to be proposed for OS patients.

目的 评价带线缆孔及大转子结合装置的锁定钢板治疗Vancouver B1型股骨假体周围骨折的临床疗效.方法 2016年1月～2021年9月我院因Vancouver B1型股骨假体周围骨折行锁定钢板联合钢缆环扎内固定治疗的病人27例(27髋).记录病人手术时间、术中出血量、住院时间、完全负重时间、髋关节Harris功能评分以及VAS疼痛评分.通过数字化X线摄片对假体、内固定钢板稳定性及骨折愈合情况进行评估.结果 27例病人均获得随访,随访时间12～58个月,平均(21.74±15.42)个月,所有病人均获得骨折愈合,未发生感染、脱位、松动及骨折不愈合、畸形愈合等,术前平均HHS功能评分和VAS疼痛评分分别为为(31.84±3.92)分、(7.63±0.97)分,术后末次随访时分别为(85.43±4.73)分、(2.00±0.78)分,经锁定钢板联合钢缆环扎内固定治疗后,HHS评分和VAS疼痛评分的临床结局均较前明显好转,差异有统计学意义(P<0.05).结论 用带线缆孔及大转子结合装置的锁定钢板对Vancouver B1型股骨假体周围骨折治疗可以取得满意的临床疗效.

BACKGROUND Long non-coding RNAs (lncRNAs) with differential expression characteristics have been found to be closely related to the tumorigenesis and development of gastric cancer (GC), but their specific mechanisms and roles still need to be further elucidated.AIM To investigate the expression of LINC01268 in GC and its mechanism of affecting GC progression.METHODS Real-time quantitative polymerase chain reaction was used to detect the expression of LINC01268 in GC tissues, cell lines and plasma. The Kaplan-Meier method was used to evaluate the value of LINC01268 in the prognostication of GC patients. An receiver operating characteristic curve was constructed to evaluate the value of LINC01268 in the diagnosis of GC. Transwell migration and invasion assays and wound healing assays were used to confirm the effect of LINC01268 on the invasion and migration of GC cells. The regulatory relationship between LINC01268 and myristoylated alanine rich protein kinase C substrate (MARCKS), the PI3K/Akt signaling pathway, and the epithelial-mesenchymal transition (EMT) process in GC was demonstrated by western blot analysis.RESULTS The expression of LINC01268 was increased in GC tissues and cell lines. The expression level of LINC01268 was significantly correlated with lymph node metastasis, TNM stage, and tumor differentiation in patients with GC. Over-expression of LINC01268 indicated a poor prognosis for patients with GC, and it had a certain auxiliary diagnostic value for GC. In vitro functional experiments proved that the abnormal expression of LINC01268 further activated the PI3K/Akt signaling pathway and promoted EMT by targeting and regulating MARCKS and ultimately promoted the invasion and metastasis of GC.CONCLUSION This study elucidates that LINC01268 in GC may be an oncogene that further activates the PI3K/Akt signaling pathway and EMT by targeting and regulating MARCKS, and ultimately promotes the invasion and metastasis of GC. LINC01268 may be a potential effective target for the treatment of GC.

OBJECTIVE:The concept of enhanced recovery after surgery (ERAS) has been proposed in recent years, which indeed bring about evident convenience for the patients. This prospective cohort study was aimed to investigate the impact of ERAS on the clinical outcome of patients who undergoing total hip arthroplasty due to displaced femoral neck fractures. METHODS:Patients in two periods were included in our research, before ERAS (n = 194) and after ERAS (n = 65). The clinical outcome, such as patient statistics, details of perioperative management, length of stay (LOS), pain, Harris hip score, in-hospital complications, and interim postoperative survival were collected. This retrospective observational study addressed confounding bias using propensity score matching (PSM) analysis. RESULTS:With PSM, 55 pairs of well-matched patients were generated for comparison (conventional vs. ERAS). LOS decreased to 13.0 ± 3.2 days for the ERAS group, compared to 15.7 ± 3.5 days in the conventional group. VAS pain scores decreased significantly in both groups, and the decrease in the ERAS group was more significant than that in the conventional group at 3, 7, and 14 days postoperatively. The Harris scores of both groups significantly improved, but were better for the ERAS group than the conventional group at 7 and 14 days and 1 month postoperatively. However, no significant difference was observed at 6 months postoperatively. Additionally, the incidence of complications during hospitalization was lower in the ERAS group than that in the conventional group. No significant difference was observed in the medium-term survival between the two groups. CONCLUSIONS:ERAS apparently benefit patients in early rehabilitation by reducing complications and shortening hospital stays but not for the long-term hip function or survival.

Immune checkpoint inhibitors (ICIs) therapy have revolutionized advanced lung cancer care. Interestingly, the host responses for patients received ICIs therapy are distinguishing from those with cytotoxic drugs, showing potential initial transient worsening of disease burden, pseudoprogression and delayed time to treatment response. Thus, a new imaging criterion to evaluate the response for immunotherapy should be developed. ICIs treatment is associated with unique adverse events, including potential life-threatening immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis) if treated patients are not managed promptly. Currently, the diagnosis and clinical management of ICI-pneumonitis remain challenging. As the clinical manifestation is often nonspecific, computed tomography (CT) scan and X-ray films play important roles in diagnosis and triage. This article reviews the complications of immunotherapy in lung cancer and illustrates various radiologic patterns of ICI-pneumonitis. Additionally, it is tried to differentiate ICI-pneumonitis from other pulmonary pathologies common to lung cancer such as radiation pneumonitis, bacterial pneumonia and coronavirus disease of 2019 (COVID-19) infection in recent months. Maybe it is challenging to distinguish radiologically but clinical presentation may help.

Objective: Osteoarthritis (OA) is a common joint disease characterized by inflammation and cartilage degeneration. Accumulating evidences support that endoplasmic reticulum (ER) stress induced OA chondrocytes apoptosis. The hypoglycemic and anti-inflammatory properties render Dapagliflozin (DAPA) effective in reducing ER stress on cells. However, its impact and potential mechanisms on the OA pathology are still obscure. The present study aimed to investigate whether DAPA attenuates ER stress in chondrocytes by activating sirt1 and delays the progression of OA.Methods: In vitro, we first investigated the effect of DAPA on chondrocytes viability with IL-1 beta or not for 24 or 48 h. Then, chondrocytes were treated with 10 ng/ml IL-1 beta and 10 mu M dapagliflozin with10 mu M thapsigargin, 5 mu M SRT1460 or not. Chondrocytes apoptosis in each group were detected by Tunel staining and flow cytometric. Immunofluorescence staining was applied to quantify the expression levels of cleaved caspase-3, Sirt1 and CHOP in chondrocytes. Inhibition of ER stress in chondrocytes associated with sirt1 activation were verified by PCR and western blotting. In addition, the effects of DAPA on cartilage were validated by a series of experiments in OA rat model, such as micro-CT, histological and immunohistochemical assay.Results: The data demonstrated that DAPA alleviates IL-1 beta induced ER stress related chondrocytes apoptosis, and PCR and western blotting data confirmed that DAPA inhibits the PERK-eIF2 alpha-CHOP pathway by activating Sirt1. Besides, immunohistochemical results showed that DAPA enhanced the expression of Sirt1 and Collagen II in OA rats, and inhibited the expression of CHOP and cleaved caspase-3. Meanwhile, histological staining and micro-CT photography also confirmed that DAPA alleviated inflammation and cartilage degeneration in OA rat.Conclusions: The study demonstrated the relationship of ER stress and inflammation in the progression of OA, and verified that DAPA could inhibit PERK-eIF2 alpha-CHOP axis of the ER stress response by activating Sirt1 in IL-1 beta treated rat chondrocytes and potentially prevent the OA development.

The present study aimed to explore the time of maximum bacterial load and main colonization knee site in bacterial infection process based on a novel rat model of septic arthritis (SA) after anterior cruciate ligament reconstruction (ACLR).Ninety-five Wistar rats with unilateral ACLR, random enrolled into control surgery (CS) group; joint inject (JI) group; presoaking (PS) group, were injected with 30 μl sterile saline or 30 μl × 107 colony forming units/ml Staphylococcus aureus via the knee joint or graft with presoaked Staphylococcus aureus during ACLR, respectively. At 1, 4, 7, 11, and 14 days postoperatively, samples were harvested to evaluate progress of knee joint infection by postoperative body weight, body temperature, knee temperature, knee width, scales of tissue damage, serum inflammatory markers, microbiological counting, microcomputed tomography (Micro-CT), digital radiography, magnetic resonance imaging (MRI) examination, and scanning electron microscopy (SEM).No systemic infection was observed in all rats. Comparing with serum inflammatory markers, tissue scores of inflammatory reactions, bacterial counts in the CS group, these data were significantly elevated in the JI group and PS group. The bone mass around the bone tunnel was lower and the soft tissue of knee showed more obvious swelling on MRI in the infection groups than that in the CS group at 7 and 14 days postoperatively. Staphylococcus aureus clusters on the surface of screw and graft were observed in the infection group. The whole colony forming units of Staphylococcus aureus maintained a continuous upward trend peaking 7 and 11 days followed by a balanced curve in the infection groups. Bone and soft tissue were found to have more bacterial counts than graft and screws.This animal model effectively mimics the acute knee infection after ACLR. We found that the bacterial colonization exhibited the peak of acute infection between 7 and 11 days postoperatively, with the major bacteria loads found in the bone, soft tissue.

BACKGROUND:The process of lactate metabolism has been proved to play a critical role in the progression of various cancers and to influence the immune microenvironment, but its potential role in osteosarcoma remains unclear.METHODS:We have acquired transcriptomic and clinical data from 84 osteosarcoma samples and 70 normal bone samples from the TARGET and GTEx databases. We identified differentially expressed lactate metabolism-related LncRNAs (LRLs) in osteosarcoma and performed Cox regression and LASSO regression to establish LRLs prognostic signature (LRPS). The reliability of LRPS performance was examined by separate prognostic analysis, viability curves and receiver operating characteristic (ROC) curves. Furthermore, the effects of LRPS on the immune microenvironment of osteosarcoma were investigated, and the functions of the focal genes were experimentally validated.RESULT:A total of 856 differentially expressed LRLs were identified and 5 of them were selected to construct LRPS, which was a better prognostic predictor for osteosarcoma compared with other published prognostic signatures (AUC up to 0.947 and 0.839 in the training and test groups, respectively, with adj-p<0.05 for KM curves). We found that LRPS significantly affected the immune infiltration of osteosarcoma, while RP11-472M19.2 significantly promoted the metastasis of osteosarcoma, which was well validated experimentally. Encouragingly, a number of sensitive drugs were identified for LRPS and RP11-472M19.2 high-risk groups.CONCLUSION:Our study shows that lactate metabolism plays a crucial role in the development of osteosarcoma and has been well validated experimentally, providing extremely important insights into the clinical treatment and in-depth research of osteosarcoma.

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents with extremely poor prognosis. Gambogenic acid (GNA), one of the major bioactive ingredients isolated from Gamboge, has been shown to possess a multipotent antitumor effect, its activity on OS remains unclear yet. In this study, we found that GNA could trigger multiple cell death modalities, including ferroptosis and apoptosis in human OS cells, reduce the cell viability, inhibit the proliferation and invasiveness. Furthermore, GNA provoked oxidative stress leading to GSH depletion-inducing ROS generation and lipid peroxidation, altered iron metabolism represented by the induction of labile iron, mitochondrial membrane potential decreased, mitochondrial morphological changed, decreased the cell viability. In addition, ferroptosis inhibitors (Fer-1) and apoptosis inhibitors (NAC) can partially reversed GNA' s effects on OS cells. Further investigation showed that GNA augmented the expression of P53, bax, caspase 3 and caspase 9 and decreased the expression of Bcl-2, SLC7A11 and glutathione peroxidase-4 (GPX4). In vivo, GNA was showed to delay tumor growth significantly in axenograft osteosarcoma mouse model. In conclusion, this study reveals that GNA simultaneously triggers ferroptosis and apoptosis in human OS cells by inducing oxidative stress via the P53/SLC7A11/GPX4 axis.

Background and objective:Lateral pelvic lymph node (LPLN) metastasis is one of the prominent reasons for local recurrence (LR) in patients with rectal cancer (RC). The evaluation criteria of lateral lymph node dissection (LLND) for patients in eastern (mainly in Japan) and western countries have been controversial. The aim of this study was to analyse the risk factors for LPLN metastasis in order to guide surgical methods. Methods:We searched relevant databases (Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science) for articles published between 1 January 2000 and 05 October 2022 to evaluate the risk factors for LPLN metastasis in patients with RC in this meta-analysis. Results:A total of 24 articles with 5843 patients were included in this study. The overall results showed that female sex, age <60 years, pretherapeutic CEA level >5 ng/ml, clinical T4 stage (cT4), clinical M1 stage (cM1), distance of the tumour from the anal verge (AV) <50 mm, tumour centre located below the peritoneal reflection (Rb), short axis (SA) of LPLN ≥8 mm before nCRT, short axis (SA) of LPLN ≥5 mm after nCRT, border irregularity of LPLN, tumour size ≥50 mm, pathological T3-4 stage (pT3-4), pathological N2 stage (pN2), mesorectal lymph node metastasis (MLNM), lymphatic invasion (LI), venous invasion (VI), CRM (+) and poor differentiation were significant risk factors for LPLN metastasis (P <0.05). Conclusion:This study summarized almost all potential risk factors of LPLN metastasis and expected to provide effective treatment strategies for patients with LRC. According to the risk factors of lateral lymph node metastasis, we can adopt different comprehensive treatment strategies. High-risk patients can perform lateral lymph node dissection to effectively reduce local recurrence; In low-risk patients, we can avoid overtreatment, reduce complications and trauma caused by lateral lymph node dissection, and maximize patient survival and quality of life.

BACKGROUND:There is growing evidence that the SNX family is critical for clinical prognosis, immune infiltration and drug sensitivity in many types of tumors. The relationships between the SNX29 gene and clinical prognosis as well as pan-cancer cell infiltration and drug sensitivity have not been fully elucidated.METHODS:In the current study, we explored the correlation between SNX29 expression and 33 types of malignancies via TCGA and GTEx. The relationship between SNX29 expression and prognostic outcome in the pan-caner cohort was also analyzed. Immune infiltration, microsatellite instability, tumor mutational burden and potential therapeutic targets of SNX29 were investigated by analyzing public databases.RESULTS:The expression of SNX29 was found to be significantly upregulated in most tumor tissues compared to normal tissues. SNX29 expression was associated with prognosis and clinical stage. In the immune infiltration analysis, a significant relationship was found between SNX29 expression and the level of immune infiltration. In addition, we found associations between the SNX29 gene and tumor mutation burden, microsatellite instability, immunoinhibition-related genes and autophagy-related genes. Finally, the expression of SNX29 was significantly associated with the sensitivity of various tumor cell lines to 8 antitumor drugs. These results suggest that SNX29 expression is important in determining the progression, immune infiltration and drug sensitivity of various cancers.CONCLUSION:This study provides novel insights into the potential pan-cancer targets of SNX29.

目的:探讨膝关节镜联合富血小板血浆(PRP)及玻璃酸钠(HA)腔内注射在早期前交叉韧带重建(ACLR)中的应用及疗效.方法:对2019年6月-2020年12月本院收治的行ACLR的患者进行回顾性分析,通过纳排标准共纳入60例患者,ACLR组20例,ACLR联合玻璃酸钠注射(ACLR+HA)组20例,ACLR联合玻璃酸钠及富血小板血浆注射(ACLR+HA+PRP)组20例.比较三组之间术前、术后的膝关节功能、关节活动度、膝关节疼痛、股骨隧道直径变化及移植肌腱的愈合情况.结果:ACLR+HA+PRP组在膝关节功能、活动度方面明显优于ACLR和ACLR+HA组;ACLR+HA+PRP组膝关节疼痛较其他两组明显降低,而且移植肌腱腱骨愈合情况较另两组更优.结论:膝关节镜联合PRP及HA腔内注射在早期前交叉韧带重建中疗效显著,明显增强了膝关节的稳定性,促进移植肌腱的愈合,改善膝关节功能.

Objective:To explore the molecular mechanism of traditional Chinese medicine monomer curcumin in alleviating osteoarthritis in rats.Methods:Totally, 30 SD rats were randomly divided into control group, arthritis group and curcumin group, with 10 rats in each group by random number table method. Rats in arthritis group and curcumin group were injected with papain to replicate the animal model of osteoarthritis. The animals in curcumin group were injected with 50 mg/kg curcumin through the articular cavity, and those in control group and arthritis group were injected with equal volume of normal saline through the articular cavity. The follow-up study was carried out after 3 weeks of continuous treatment. The maximum range of motion and synovial thickness of the knee joint in the three groups were measured. The content of glycosaminoglycan in the synovial supernatant in the three groups was determined by spectrophotometry. The degree of arthritis was analyzed by Mankin histological score. The levels of inflammatory factors in synovial fluid were analyzed by enzyme linked immunosorbent assay (ELISA). Masson staining was used to analyze the content of collagen fibers in knee joint. One way ANOVA was used for comparison between groups.Results:The maximum knee flexion and extension angle [(136.87±6.42) °] in curcumin group were significantly lower than those in arthritis group [(156.81±13.90) °, t=4.714, P<0.05]. The Mankin score of knee joint in curcumin group (2.36±0.24) was significantly higher than that in arthritis group (1.50±0.29, t=18.051, P<0.05). The glycosaminoglycan level in curcumin group [(501.90±26.92) ng/mg] was significantly higher than that in arthritis group [(445.80±49.22) ng/mg, t=3.162, P<0.05]. Tumor necrosis factor-α (TNF-α) and interleukin (IL)-1 β in knee joint of rats in curcumin group [(143.33±20.58), (41.20±5.98) ng/mg] were significantly lower than those in arthritis group[(255.28±51.48), (101.03±14.21) ng/mg, t=6.386, 12.272, P<0.05]. The expression level of p-p65 protein in curcumin group (1.49±0.13) was significantly lower than that in arthritis group (2.36±0.37, t=7.063, P<0.05). Conclusion:Curcumin can significantly reduce the level of arthritis, promote the synthesis of collagen fibers in damaged joints and alleviate the symptoms of osteoarthritis.

Ferroptosis, a novel form of regulated cell death characterized by disrupted iron metabolism and the accumulation of lipid peroxides, has exhibited enormous potential in the therapy of cancer particularly clear cell renal cell carcinoma (ccRCC). Luteolin (Lut), a natural flavonoid widely existing in various fruits and vegetables, has been proven to exert potent anticancer activity in vitro and in vivo. However, previous studies on the anticancer mechanism of Lut have been shown in apoptosis but not ferroptosis. In the present study, we identified that Lut substantially inhibited the survival of ccRCC in vitro and in vivo, and this phenomenon was accompanied by excessively increased intracellular Fe2+ and abnormal depletion of GSH. In addition, Lut induced the imbalance of mitochondrial membrane potential, classical morphological alterations of mitochondrial ferroptosis, generation of ROS, and occurrence of lipid peroxidation in an iron-dependent manner in ccRCC cells. However, these alterations induced by Lut could be reversed to some extent by the iron ion chelator deferiprone or the ferroptosis inhibitor ferrostatin-1, indicating that ccRCC cells treated with Lut underwent ferroptosis. Mechanistically, molecular docking further established that Lut probably promoted the heme degradation and accumulation of labile iron pool (LIP) by excessively upregulating the HO-1 expression, which led to the Fenton reaction, GSH depletion, and lipid peroxidation in ccRCC, whereas blocking this signaling pathway evidently rescued the Lut-induced cell death of ccRCC by inhibiting ferroptosis. Altogether, the current study shows that the natural compound monomer Lut exerted anticancer efficacy by excessively upregulating HO-1 expression and activating LIP to trigger ferroptosis in ccRCC and could be a promising and potent drug candidate for ccRCC treatment.