1.Hyaluronan-mediated motility receptor-mediated aerobic glycolysis enhances stem-like properties and chemoresistance in lung adenocarcinoma
Wenwen YU ; Yubo SHI ; Xiaoqiong BAO ; Xiangxiang CHEN ; Yangyang NI ; Jincong WANG ; Hua YE
The Korean Journal of Physiology and Pharmacology 2025;29(3):337-347
Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.
2.Hyaluronan-mediated motility receptor-mediated aerobic glycolysis enhances stem-like properties and chemoresistance in lung adenocarcinoma
Wenwen YU ; Yubo SHI ; Xiaoqiong BAO ; Xiangxiang CHEN ; Yangyang NI ; Jincong WANG ; Hua YE
The Korean Journal of Physiology and Pharmacology 2025;29(3):337-347
Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.
3.Hyaluronan-mediated motility receptor-mediated aerobic glycolysis enhances stem-like properties and chemoresistance in lung adenocarcinoma
Wenwen YU ; Yubo SHI ; Xiaoqiong BAO ; Xiangxiang CHEN ; Yangyang NI ; Jincong WANG ; Hua YE
The Korean Journal of Physiology and Pharmacology 2025;29(3):337-347
Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.
4.Hyaluronan-mediated motility receptor-mediated aerobic glycolysis enhances stem-like properties and chemoresistance in lung adenocarcinoma
Wenwen YU ; Yubo SHI ; Xiaoqiong BAO ; Xiangxiang CHEN ; Yangyang NI ; Jincong WANG ; Hua YE
The Korean Journal of Physiology and Pharmacology 2025;29(3):337-347
Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.
5.Hyaluronan-mediated motility receptor-mediated aerobic glycolysis enhances stem-like properties and chemoresistance in lung adenocarcinoma
Wenwen YU ; Yubo SHI ; Xiaoqiong BAO ; Xiangxiang CHEN ; Yangyang NI ; Jincong WANG ; Hua YE
The Korean Journal of Physiology and Pharmacology 2025;29(3):337-347
Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.
6.Comparison of clinical outcome between the percutaneous pedicle screw fixation and Wiltse approach for the treatment of thoracolumbar fractures without neurological injury
Mengmeng CHEN ; Pu JIA ; Hao CHEN ; Li BAO ; Guan SHI ; Fei FENG ; Shuangjiang ZHANG ; Hai TANG
International Journal of Surgery 2024;51(3):159-165
Objective:To compare the safety and efficacy of two different minimally invasive approaches to implant pedicle screw for the treatment of single-segment thoracolumbar spine fractures without nerve injury.Methods:This was a retrospective study. Eighty patients with mono-segmental thoracolumbar fractures treated with minimally invasive pedicle screw fixation at Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2022 were included. There were 46 males and 36 females, the age was (45.93±7.91) years old, and ranged from 27 to 60 years old. They were divided into two groups according to different surgical techniques: percutaneous pedicle screw fixation group ( n=44) and Wiltse approach group ( n=36). The operative time, operative visible blood loss, hidden blood loss, total blood loss, fluoroscopy times, incision length, hospital time after surgery and ambulation time were compared. Visual analogue scale (VAS), Oswestry disability index (ODI), ratio of the vertebral anterior height, angle of injured vertebral endplate were recorded and compared between two groups before surgery and at 3 days, 6 months and 1 year after surgery. The accuracy of pedicle screw position and the facet joint violation rate were evaluated by using the postoperative CT scan. Perioperative related complications were investigated. Normally distributed numerical data were presented as mean ± standard deviation, and differences between the groups were compared using t-test. The counting data were expressed as percentages or rates and compared using χ2 test. Results:All patients were followed for a minimum of 12 months. There is no significant difference between the two groups in intraoperative visible blood loss, hospital time after surgery, ambulation time, postoperative VAS and ODI, ratio of vertebral anterior height and angle of injured vertebral endplate at 3 days after surgery, pedicle screw position accuracy and perioperative complications ( P>0.05). The operative time, hidden blood loss, total blood loss, intraoperative fluoroscopy times, facet joint violation rate in the percutaneous pedicle screw fixation group were remarkably higher than in the Wiltse approach group ( P<0.05). The ratio of vertebral anterior height in the percutaneous pedicle screw fixation group was dramatically lower than in the Wiltse approach group at 6 months and 1 year after surgery ( P<0.05). The postoperative injured vertebral endplate angle was higher in the percutaneous pedicle screw fixation group than that in the Wiltse approach group at 6 months and 1 year ( P<0.05). Conclusions:Both percutaneous pedicle screw fixation and Wiltse approach were safe and effective minimally invasive surgical procedures for the treatment of thoracolumbar fractures without neurological injury. The Wiltse approach can reduce fluoroscopy times and perioperative hidden blood loss, reduce the risk of facet joint violation, and maintain a better reduction than percutaneous pedicle screw fixation.
7.Biomechanical characteristics of a novel interspinous distraction fusion device BacFuse for the repair of lumbar degenerative disease
Mengmeng CHEN ; Li BAO ; Hao CHEN ; Pu JIA ; Fei FENG ; Guan SHI ; Hai TANG
Chinese Journal of Tissue Engineering Research 2024;28(9):1325-1329
BACKGROUND:Interspinous distraction fusion device BacFuse was used for the management of lumbar degenerative disease and obtained good clinical efficacy in recent years.However,the related biomechanical study was lacking. OBJECTIVE:To explore the related biomechanical characteristics of BacFuse,a novel interspinous distraction fusion device,which was used in lumbar degenerative disease. METHODS:After constructing the goat spinal models(L1-L6),they were grouped into four groups based on different simulated surgeries:the control group,the BacFuse group(L3/4),the screw-rod fixation group(L3/4)and the Topping-off group(L3/4 screw-rod fixation + L2/3 BacFuse fixation).The goat lumbar spine surgical model was assembled into a biomechanical testing system.A biomechanical machine was used for mechanical loading,simulating lumbar spine movement of flexion,extension,lateral flexion and rotation with a 4 Nm moment.A visual tracking system was used for positioning and capturing.Finally,mechanical and optical calibration was completed to calculate the range of motion of the L2/3,L3/4 and L4/5 segments. RESULTS AND CONCLUSION:(1)Compared with the control group,the range of motion of the L3/4 segment in the BacFuse group decreased 27.27%,70%,38.1%and 23.08%in the flexion,extension,lateral bending and rotation directions,respectively(P<0.05).The range of motion of L3/4 segment in the screw-rod fixation group decreased 72.73%,80%,71.43%and 73.08%in the flexion,extension,lateral bending and rotation directions,respectively(P<0.05).(2)Compared with the control group,the range of motion of the adjacent segment L2/3 increased by 33.33%,25%and 23.81%in the extension,lateral bending and rotation directions,respectively in the BacFuse group(P<0.05),with no significant change in flexion.In the screw-rod fixation group,there was a 50%,44.44%,50%and 58.96%increase in the adjacent segment L2/3 in the flexion,extension,lateral calibration and rotation directions,respectively(P<0.05).(3)Compared with the control group,the BacFuse group showed an increase in range of motion in proximal segment L4/5 in the extension and rotation directions by 27.3%and 17.39%(P<0.05)respectively,with no significant change in flexion or lateral bending.In the screw-rob fixation group,the proximal segment L4/5 demonstrated 38.89%,22.73%and 26.09%(P<0.05)increases in range of motion in the flexion,extension and rotation directions,respectively,with no significant change in lateral bending.(4)In the Topping-off group,the range of motion of L2/3 was reduced by 37.04%,73.08%,56.67%and 38.46%in flexion,extension,lateral flexion and rotation,respectively,compared to the screw-rob fixation group(P<0.05).Compared with the screw-rob fixation group,the Topping-off group showed a 20%reduction in the range of motion of the L4/5 in the flexion direction(P<0.05),with no significant differences seen in extension,lateral bending and rotation.(5)It is concluded that the interspinous distraction fusion device BacFuse significantly reduces the range of motion of the implanted segment and provides some stability.It still retains more mobility and reduces the impact on the adjacent segment compared to screw-rob fixation,while the Topping-off tip,which can be used for intervertebral fusion fixation,significantly reduces the range of motion of the adjacent segment and reduces the risk of adjacent segment degeneration.
8.Low-frequency pulsed magnetic field induces classical transient receptor potential channels 1 to relieve lower limb muscle weakness in patients recovering from COVID-19
Zhongshan LI ; Yijun BAO ; Jie LIU ; Weiqian KONG ; Wei LI ; Lin CHEN ; Shi BAI ; Tieli YANG ; Chunlu WANG
Chinese Journal of Tissue Engineering Research 2024;28(16):2605-2612
BACKGROUND:Muscle weakness is a common symptom after coronavirus disease 2019(COVID-19)infection and affects the ability to perform daily activities in humans during recovery.Low-frequency pulsed magnetic field stimulation at a strength of 1.5 mT and a frequency of 3 300 Hz can enhance the maximal voluntary contraction and strength endurance of human skeletal muscle by inducing and activating classical transient receptor potential channel 1(TRPC1),which produces a series of pathological support effects on muscle tissue.It has not been studied whether this means will improve muscle weakness in patients recovering from COVID-19. OBJECTIVE:To select the low-frequency pulsed magnetic field for magnetic stimulation of lower limb muscle groups in patients with COVID-19,in order to observe the effect of this stimulation on the improvement of muscle weakness of lower limb muscle groups in patients with COVID-19 during the recovery period. METHODS:Fourteen patients infected with COVID-19(Omicron strain)positive for Innovita COVID-19 Ab Test(Colloidal Gold)and accompanied by muscle weakness were recruited and randomly divided into two groups:a test group receiving magnetic field stimulation and a control group receiving sham treatment,respectively.The total duration of the trial was 3 weeks.The test group was given low-frequency pulsed magnetic stimulation of the lower limbs every 48 hours and the control group was given the same intervention procedure as the test group but with sham stimulation.Patients in both groups were not informed whether the magnetic stimulation apparatus was running or not.Nine sessions were performed in both groups and the changes in the maximum voluntary contraction,explosive leg force and strength endurance of the local muscle groups of the lower limbs were subsequently observed in both groups. RESULTS AND CONCLUSION:Among the eight local muscle groups collected,seven local muscle groups in the test group showed an increase in the maximum voluntary contraction value after 3 weeks of low-frequency pulsed magnetic field stimulation.In the control group,there were only three muscle groups with improvement in the maximum voluntary contraction.The rate of improvement in the anterior and posterior muscle groups of the left leg in the test group was significantly higher than that in the control group.The longitudinal jump height and peak angular velocity of the knee joint in both groups were improved compared with the pre-test measurement,and the elevation rate of jumping height in the test group was higher than that in the control group.Under the fatigue condition,the decline rates of peak angular velocity of the knee joint and jumping height in the test group decreased significantly,while those in the control group did not change significantly.The above data confirmed that the low-frequency pulsed magnetic field stimulation with the intensity of 1.5 mT and frequency of 3 300 Hz could improve the muscle strength of more local muscle groups in the lower limbs of patients with COVID-19 during the recovery period compared with the human self-healing process,and the whole-body coordination ability and functional status based on explosive leg force of the legs could be significantly improved.Therefore,low-frequency pulsed magnetic field stimulation can be used as an effective,non-exercise rehabilitation tool to improve muscle weakness in the lower limbs of patients with COVID-19.
9.Effects of cognition-related lifestyles on early cognitive decline in community older adults in China
Haowei LI ; Shige QI ; Shengshu WANG ; Shanshan YANG ; Shimin CHEN ; Rongrong LI ; Xuehang LI ; Shaohua LIU ; Junhan YANG ; Huaihao LI ; Yinghui BAO ; Yueting SHI ; Zhihui WANG ; Yao HE ; Miao LIU
Chinese Journal of Epidemiology 2024;45(1):63-70
Objective:To investigate the distribution characteristics of cognition-related lifestyles of elderly in communities and explore the integrated effects on early cognitive decline.Methods:The participants were from the Project of Prevention and Intervention of Neurodegenerative Disease for Elderly in China. A total of 2 537 older adults aged ≥60 years without dementia in the 2015 baseline survey and the 2017 follow-up survey were included. The information about their cognition-related lifestyles, including physical exercise, social interaction, leisure activity, sleep quality, smoking status, and alcohol consumption, were collected through questionnaire survey and the integrated scores were calculated. Multivariate logistic regression analysis was used to assess the association between integrated cognition-related lifestyle score and early cognitive decline.Results:In the 2 537 older adults surveyed, 28.7% had score of 5-6, while only 4.8% had high scores for all 6 healthy lifestyles. Significant differences in healthy lifestyle factor distributions were observed between men and women. Multivariate logistic regression model showed that the risks for early cognitive decline in the older adults who had lifestyle score of 4 and 5-6 were lower than that in those with lifestyle score of 0-3 ( OR=0.683, 95% CI: 0.457-1.019; OR=0.623, 95% CI: 0.398-0.976; trend P=0.030). In the women, the risks for early cognitive decline was lower in groups with score of 4 and 5-6 than in group with score of 0-3 ( OR=0.491, 95% CI: 0.297-0.812; OR=0.556, 95% CI: 0.332-0.929; trend P=0.024). Conclusion:Cognition-related healthy lifestyles are associated with significantly lower risk for early cognitive decline in the elderly, especially in women.
10.Evaluation of the efficacy of percutaneous vertebroplasty for the treatment of multi-segment osteolytic spinal metastatic tumors
Hao CHEN ; Guan SHI ; Li BAO ; Pu JIA
International Journal of Surgery 2024;51(7):454-460
Objective:To analyze the safety and efficacy of single percutaneous vertebroplasty (PVP) in the treatment of multi-segment osteolytic spinal metastases.Methods:A retrospective analysis was conducted on 113 patients with multi-segment osteolytic spinal metastases treated with PVP at Beijing Friendship Hospital, Capital Medical University from January 2013 to December 2019, including 50 males and 63 females. The age ranged from 47 to 85 years, with a mean of (66.9±1.52) years. Patients were divided into two groups based on the number of affected vertebrae undergoing surgery: the conventional surgery group ( n=72), with a maximum of three vertebral bodies undergoing PVP during each surgery; the multivertebral surgery group ( n=41), received PVP on more than three vertebral bodies in one surgery. Visual analogue scale(VAS) of pain, Oswestry disability index (ODI), general health status (GH), and mental health status (MH) were assessed before and after PVP to evaluate the efficacy of the procedure. Complications of the patients were systematically assessed to evaluate safety. Measurement data was expressed as mean±standard deviation( ± s), independent sample t-test was used for inter-group comparison, and paired sample t-test was used for intra-group comparison; the comparison of count data was conducted using Chi-square test. Results:After 6 months of surgery, the ODI score, GH score and MH score of the conventional surgery group was (35.28±1.74)%, 57.85±2.11 and 61.20±3.67, all of which improved significantly compared to before surgery, and the difference was statistically significant ( P<0.05). After 6 months of surgery, the ODI score, GH score and MH score of the multivertebral surgery group was (35.67±1.92)%, 64.12±1.35 and 59.80±3.81, all of which improved significantly compared to before surgery, and the difference was statistically significant ( P<0.05). There was no significant difference in ODI score and MH score between the two groups after 6 months of surgery ( P>0.05). At one week after surgery, the pain VAS score in the conventional surgery group (3.51±0.21) was lower than that in the multivertebral surgery group (3.98±0.32), and the difference was statistically significant ( P<0.05). GH score in the conventional surgery group showed significantly greater improvement than that in the multivertebral surgery group after 6 months of surgery, and the difference was statistically significant ( P<0.05). Bone cement leakage occurred in 21 vertebra of the conventional surgery group, and 24 vertebra of the multivertebral surgery group, with leakage rates of 14.8% and 13.0%, respectively, with no statistical significance between the two groups ( P>0.05). Conclusions:Single PVP surgery can safely and effectively alleviate the pain of multi-segment osteolytic spinal metastases and improve spinal mobility. Meanwhile, improving mental health and reducing functional impairments. But the short-term pain relief and long-term general health of the multivertebral surgery group were lower than those of the conventional surgery group.

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