BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Eight butyl-phthalides, senkyunolide K(1), senkyunolide N(2), butylphthalide(3), senkyunolide I(4), senkyunolide H(5),(Z)-butylidenephthalide(6),(Z)-ligustilide(7), and 3-butylidene-7-hydroxyphthalide(8) were isolated from the aerial part of Ligusticum sinense by column chromatography on silica gel column, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic and chemical data, especially NMR and MS. Compound 1 was a new butyl-phthalide and compounds 2-8 were isolated from the aerial part of L. sinense for the first time. Furthermore, the inhibitory activities of compounds 1-8 against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse RAW264.7 macrophages in vitro were evaluated. The results showed that compounds 1-8 exerted inhibitory activities on NO production with IC_(50) of 19.34-42.16 μmol·L~(-1).
Animals ; Mice ; Nitric Oxide/biosynthesis* ; Ligusticum/chemistry* ; Benzofurans/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Macrophages/immunology* ; RAW 264.7 Cells ; Molecular Structure

OBJECTIVE: To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease. METHODS: A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment. RESULTS: A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group. CONCLUSION After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans ; Male ; Female ; Intervertebral Disc Displacement/drug therapy* ; Adult ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Lumbar Vertebrae

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Objective To analyse the acupoint selection rules of acupuncture in the treatment of non-small cell lung cancer,and to provide reference for clinical application.Methods The clinical research,practitioner's experience and academic thought of acupuncture treatment for non-small cell lung cancer were retrieved to obtain the acupuncture prescriptions of modern practitioners for the treatment of non-small cell lung cancer.Based on the statistical methods of acupoint frequency,prescription rules,acupoint clustering and core combination,the core theoretical system and acupoint selection rules of acupuncture treatment of non-small cell lung cancer by modern practitioner were analyzed.Results According to the inclusion and exclusion criteria,94 acupuncture prescriptions were finally included.There were eight acupoints used more than 20 times,which were Zusanli(ST36),Neiguan(PC6),Feishu(BL13),Sanyinjiao(SP6),Qihai(RN6),Guanyuan(RN4),Hegu(LI4)and Zhongwan(RN12).The top three high-frequency acupoint combinations were Zusanli-Neiguan,Zusanli-Sanyinjiao and Qihai-Zusanli;correlation analysis showed that the correlation strength of Zusanli-Neiguan was the highest,followed by Zusanli-Sanyinjiao and Zusanli-Hegu.The cluster analysis showed that the acupoints with frequency＞10 times could be divided into three categories.Category 1 includes:Zusanli,Neiguan,Sanyinjiao,Hegu;category 2 includes Guanyuan,Qihai,Zhongwan,Xuehai(SP10),Taichong(LR3);category 3 consists of two parts,one is Danzhong(RN17),Tiantu(RN22),Fenglong(ST40),Taiyuan(LU9);the second is Feishu(BL13),Lieque(LU7),Chize(LU5),Zhongfu(LU1),Xinshu(BL15),Gaohuang(BL43),Fengmen(BL12).Conclusion The core acupoints for acupuncture treatment of non-small cell lung cancer include four categories:① invigorating the spleen and benefiting qi:Zusanli,Sanyinjiao,Zhongwan and Fenglong;②replenishing and supplementing original qi:Guanyuan,Qihai and Gaohuang;③regulating qi and broadening the chest:Danzhong,Neiguan,Tiantu and Fengmen;④ diffusing the lung and ventilating qi:Feishu,Hegu,Chize and Lieque.The three treatment methods of replenishing qi,regulating qi and venting pathogen are the basis of acupuncture treatment of advanced non-small cell lung cancer.The core idea of acupuncture treatment of non-small cell lung cancer focuses on supplementation,supplemented by dredging,and to dredge and supplement simultaneously.

Purpose::To explore the clinical characteristics of pediatric pelvic fracturs caused by traffic accidents and to analyze the accompanying injuries and complications.Methods::A total of 222 cases involved traffic accidents was enrolled in this case-control study. The data of children with pelvic fractures caused by traffic accidents who were admitted to our hospital from January 2006 to December 2021 were analyzed retrospectively. Sex, age, Tile classification, abbreviated injury scale score, injury severity score, mortality, and accompanying injuries were studied. The ANOVA was used for measurement data, and the non-parametric rank sum test was used for non-normally distributed data. The Fisher's exact probability method was used for the count data.Results::Of all enrolled cases, 140 are boys and 82 are girls, including 144 cases aged < 6 years, 65 aged between 6 and 12 years, and 13 aged > 12 years. Depending on the injury mechanism, there are 15 cases involving pedestrians vs. motorcycles (PVM), 91 cases involving pedestrians vs. passenger cars (PVC), 78 cases involving pedestrians vs. commercial vehicles (PVV), and 38 cases involving motor vehicles vs. motor vehicles (MVM). Associated injuries are reported in 198 cases (89.2%), primarily involving the abdomen injury in 144 cases (64.9%), and lower limb injury in 99 cases (44.6%). PVV injury involves longer hospital stay ( p =0.004). Intensive care unit admission rate is significantly higher in the MVM group than in other groups ( p =0.004). Head injury ( p =0.001) and face injury ( p =0.037) are more common in the MVM group, whereas abdominal injury ( p =0.048) and lower limb injury ( p =0.037) are more common in the PVV group. In the MVM group, the brain injury ( p =0.004) and femoral neck injury ( p =0.044) are more common. In the PVM group, the mediastinum ( p =0.004), ear ( p =0.009), lumbar vertebrae ( p =0.008), and spinal cord ( p =0.011) are the most vulnerable regions, while in the PVV group, the perineum ( p < 0.001), urethra ( p =0.001), rectum ( p =0.006), anus ( p =0.004), and lower limb soft tissues ( p =0.024) are the most vulnerable regions. Children aged > 12 years have higher pelvic abbreviated injury scale scores ( p =0.019). There are significant differences in the classification of pelvic fractures among children < 6, 6 -12, and > 12 years of age, with Tile C being more likely to occur in children > 12 years of age ( p =0.033). Children aged > 12 years are more likely to sustain injuries to the spleen ( p =0.022), kidneys ( p =0.019), pancreas ( p < 0.001), lumbar vertebrae ( p =0.013), and sacrum ( p =0.024). The MVM group has the highest complication rate ( p =0.003). Conclusion::PVC is the leading cause of the abdomen and lower extremities injury and has the most concomitant injuries. Different traffic injuries often lead to different associated injuries. Older children are more likely to sustain more severe pelvic fractures and peripelvic organs injuries. The MVM group has the highest extent of injury and complication rates.

Objective To investigate the identification of octreotide(OCT)modified chitosan(CS)miR-155 molecular beacon nanoparticles(CS-miR-155-MB-OCT)and imaging of lung cancer cells for the early screening of lung cancer.Methods A nude mouse model of lung transplantation tumor was established by injecting A549 lung cancer cells into tail veins to establish lung xenograft models.Cre adenovirus was injected through nasal cavity,and mice were killed at 4,6,8 and 12 weeks after adenovirus injection to establish lung cancer models of atypical hyperplasia,adenoma,carcinoma in situ and adenocarcinoma of lung in LSL K-ras G12D transgenic mice at different pathological stages.Lung tissue samples were taken and observed by HE staining.Immunohistochemistry were used to detect the expression of somatostatin receptor 2(SSTR2).Real-time fluorescence quantitative PCR was used to detect miR-155 expression levels in lung xenograft models and transgenic mice at different stages of lung cancer.Then CS-miR-155-MB and CS-miR-155-MB-OCT were injected via tail vein in lung xenograft models.CS-miR-155-MB-OCT was injected via tail vein in transgenic mice models.The fluorescence signals of lung in nude mice and transgenic mice at different disease stages were imaged by living imaging system.Frozen slices of lung tissue were made.The source of fluorescence signal was detected by laser confocal scanning microscope(CLSM).Results HE staining showed that lung transplantation tumor models and lung cancer models of atypical hyperplasia,adenoma,carcinoma in situ and lung adenocarcinoma at different pathological stages were successfully constructed.Immunohistochemical analysis showed somatostatin receptor 2(SSTR2)was expressed in transplanted lung tumor and tissue at different pathological stages.In transgenic mouse models,the expression of miR-155 was gradually increased as the disease progressed(P＜0.05).In lung xenograft models,the fluorescence signals were significantly higher in the CS-miR-155-MB-OCT group than those of the CS-miR-155-MB group(P＜0.05).In transgenic mouse models,the fluorescence signals gradually increased with the gradual progression of lesions(P＜0.05).After re-imaging the lung tissue,it was found that the fluorescence signal came from lung,and CLSM showed that the fluorescence signal came from cancer cells and some normal alveolar epithelial cells.Conclusion CS-miR-155-MB-OCT can dynamically reflect the occurrence and development of lung cancer according to changes of different fluorescence intensity,thus providing a new technology for the early diagnosis of lung cancer.

Objective: To determine the inhibitory effects of pachymic acid on lung adenocarcinoma (LUAD) cells and elucidate its underlying mechanism. Methods: CCK-8, wound healing, Transwell, Western blot, tube formation, and immunofluorescence assays were carried out to measure the effects of various concentrations of pachymic acid on LUAD cell proliferation, metastasis, angiogenesis as well as autophagy. Subsequently, molecular docking technology was used to detect the potential targeted binding association between pachymic acid and protein tyrosine phosphatase 1B (PTP1B). Moreover, PTP1B was overexpressed in A549 cells to detect the specific mechanisms of pachymic acid. Results: Pachymic acid suppressed LUAD cell viability, metastasis as well as angiogenesis while inducing cell autophagy. It also targeted PTP1B and lowered PTP1B expression. However, PTP1B overexpression reversed the effects of pachymic acid on metastasis, angiogenesis, and autophagy as well as the expression of Wnt3a and β-catenin in LUAD cells. Conclusions: Pachymic acid inhibits metastasis and angiogenesis, and promotes autophagy in LUAD cells by modulating the Wnt/ β-catenin signaling pathway via targeting PTP1B.

Objective To investigate the risk factors of periprosthetic femoral fracture(PFF)after total knee arthroplasty(TKA)in the elderly and to construct a predictive model for the prevention of PFF after clinical operation.Methods The clinical data of 537 elderly patients who underwent TKA in the orthopedic department of the First Affiliated Hospital of Air Medical University from October 2016 to October 2021 were retrospectively analyzed.The occurrence of PFF during the follow-up period was statistically analyzed and the clinical data were collected.Binary Logistic regression was used to analyze the risk factors of PFF after TKA in the elderly,and a predictive model of PFF after TKA in the elderly was constructed based on the risk factors.Receiver operating characteristic(ROC)curve and Hosmer-Lemeshow(H-L)were used to test the discrimination and calibration of prediction model.Results The patients were followed up for 12 to 72 months after discharge,with a median time of 47 months.During the follow-up period,31 patients(5.77%)developed PFF.Age,osteoporosis,Parkinson's disease and anterior femoral notch(AFN)were the risk factors for PFF after TKA in the elderly(P<0.05),and cross fixation of prosthesis and bone cement fixation were the protective factors(P<0.05).The results of H-L test showed that the risk prediction model of PFF after TKA in the elderly had good calibration(P>0.05).ROC curve analysis showed that the risk prediction model of PFF after TKA in the elderly has high discrimination(area under the curve was 0.858,95%CI:0.826 to 0.887),the sensitivity was 83.87%,the specificity was 88.34%.Conclusion The risk of PFF after TKA in the elderly is high,and prevention should be carried out according to the high risk factors.The prediction model constructed based on the high risk factors has good prediction efficiency.