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.Effect of Huangqi Danzhi Shenmai Decoction in coronary atherosclerosis patients with qi deficiency and blood stasis syndrome and its impact on serum oxidative stress indicators and inflammatory factors
Yujiang WU ; Rongqi BAO ; Jiahao CHEN ; Jiayu YU ; Yueqing DAI
Journal of Clinical Medicine in Practice 2025;29(19):37-40,52
Objective To explore the effect of Huangqi Danzhi Shenmai Decoction in treatment of coronary atherosclerosis patients with qi deficiency and blood stasis syndrome and its influence on the levels of serum malondialdehyde(MDA),superoxide dismutase(SOD),tumor necrosis factor-α(TNF-α),and interleukin-1 β(IL-1β).Methods A total of 120 patients with coronary atheroscle-rosis were selected and randomly divided into control group(conventional treatment+simvastatin)and observation group(conventional treatment+Huangqi Danzhi Shenmai Decoction)by random number table method,with 60 cases in each group.The clinical efficacy of the two groups was evalua-ted.The changes in traditional Chinese medicine(TCM)syndrome scores,blood lipids,inflammatory factors,and oxidative stress indicators before and after treatment were recorded for both groups.Re-sults The total effective rate in the observation group was higher than that in the control group(P<0.05).After treatment,the TCM syndrome scores in the observation group were lower than those in the control group(P<0.05).The improvement in blood lipid indicators was more pronounced in the observation group compared to the control group(P<0.05).The serum levels of TNF-α,IL-1 β,and MDA in the observation group were lower than those in the control group,while the serum levels of SOD and glutathione peroxidase(GSH-PX)were higher than those in the control group,with statis-tically significant differences(P<0.05).No severe adverse reactions occurred in either group dur-ing the treatment period.Conclusion Huangqi Danzhi Shenmai Decoction has a good clinical effi-cacy in treating coronary atherosclerosis with qi deficiency and blood stasis syndrome,and can im-prove the oxidative stress status,reduce inflammatory responses,and regulate blood lipid levels in patients,so it is worthy of clinical promotion and use.
3.A finite element method biomechanical study of a new type of composite anterior cervical internal fixation methods.
Zhi-Peng HOU ; Sen-Qi YE ; Ji-Hui ZHANG ; Liu-Jun ZHAO ; Yong-Jie GU ; Liang YU
China Journal of Orthopaedics and Traumatology 2025;38(11):1156-1163
OBJECTIVE:
To compare the biomechanical properties of four internal fixation methods in a lower cervical spine injury model using the finite element method.
METHODS:
Cervical CT data of a 28-year-old healthy adult male were utilized to establish a finite element model of the normal cervical spine and a lower cervical spine three-column injury model. Four internal fixation methods were then applied to the three-column injury model, resulting in four groups:Group A, anterior cervical locked-plate(ACLP) fixation system model(anterior approach);Group B, posterior cervical pedicle screw fixation model (posterior approach);Group C, combined anterior and posterior cervical pedicle screw fixation model; Group D, Novel composite anterior cervical internal fixation model. A 75 N axial compressive load and a 1.0 N·m pure moment were applied to the upper surface of the cervical spine model to simulate flexion, extension, rotation, and lateral bending movements. The intervertebral range of motion(ROM) and stress distribution of the internal fixators under different motion conditions were compared across all models.
RESULTS:
Compared with the normal model, the reductions in overall intervertebral ROM for each group under flexion, extension, rotation, and lateral bending were as follows:Group A, 24.04°, 23.12°, 6.24°, and 9.06°;Group B, 24.42°, 24.34°, 6.48°, and 9.20°;Group C, 25.43°, 25.29°, 7.17°, and 9.57°;Group D, 24.75°, 25.5°, 6.71°, and 9.12°. The peak stress values of the internal fixators in each group were:Group A, 53.9 MPa, 79.9 MPa, 61.4 MPa, and 80.3 MPa;Group B, 218.3 MPa, 105.4 MPa, 206.6 MPa, and 186.8 MPa;Group C, 40.8 MPa, 97.2 MPa, 47.1 MPa, and 39.4 MPa;Group D, 93.0 MPa, 144.0 MPa, 64.8 MPa, and 106.3 MPa.
CONCLUSION
The biomechanical properties of the novel composite anterior cervical internal fixation method are similar to those of the combined anterior-posterior fixation method, and superior to both the anterior cervical ACLP plate-screw fixation and posterior cervical pedicle screw fixation methods.
Humans
;
Finite Element Analysis
;
Cervical Vertebrae/physiopathology*
;
Male
;
Biomechanical Phenomena
;
Adult
;
Fracture Fixation, Internal/methods*
;
Range of Motion, Articular
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.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.
7.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.
8.Clinical study of intracranial hypotension targeted body posture combined with pharmacotherapy in the treatment of chronic subdural hematoma
Jiayu CHEN ; Zhe WANG ; Di ZANG ; Ruizhe ZHENG ; Xiangru YE ; Zengxin QI ; Zeyu XU ; Zhiqiang LI ; Chengfeng SUN ; Liangjun SHEN ; Luoping SHENG ; Fulin XU ; Ruyong YE ; Kaiyu ZHOU ; Weijun TANG ; Yueqing HU ; Dapeng SHI ; Yuquan WANG ; Xizhen WU ; Ying WANG ; Qilin ZHANG ; Feili LIU ; Guo YU ; Yiping LU ; Yirui SUN ; Ning ZHANG ; Feng HUANG ; Xialong GU ; Han ZHANG ; Jian DING ; Yongyan BI ; Haolan DU ; Jing ZHANG ; Hailong JI ; Ding DING ; Wei ZHANG ; Xuehai WU
Chinese Journal of Surgery 2025;63(3):212-218
Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.
9.Clinical study of intracranial hypotension targeted body posture combined with pharmacotherapy in the treatment of chronic subdural hematoma
Jiayu CHEN ; Zhe WANG ; Di ZANG ; Ruizhe ZHENG ; Xiangru YE ; Zengxin QI ; Zeyu XU ; Zhiqiang LI ; Chengfeng SUN ; Liangjun SHEN ; Luoping SHENG ; Fulin XU ; Ruyong YE ; Kaiyu ZHOU ; Weijun TANG ; Yueqing HU ; Dapeng SHI ; Yuquan WANG ; Xizhen WU ; Ying WANG ; Qilin ZHANG ; Feili LIU ; Guo YU ; Yiping LU ; Yirui SUN ; Ning ZHANG ; Feng HUANG ; Xialong GU ; Han ZHANG ; Jian DING ; Yongyan BI ; Haolan DU ; Jing ZHANG ; Hailong JI ; Ding DING ; Wei ZHANG ; Xuehai WU
Chinese Journal of Surgery 2025;63(3):212-218
Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.
10.Research progress on the relationship between regulatory cell death and dilated cardiomyopathy
Yueqing QIU ; Zhentao WANG ; Zhenyi CHEN ; Hongbo CHANG ; Xiaoyang YU ; Yikun XUE
Chinese Journal of Comparative Medicine 2024;34(5):113-125
Dilated cardiomyopathy(DCM)has a concealed onset with left or even whole heart enlargement as the main imaging manifestation.It is a common primary disease of heart failure and arrhythmia.With the continuous deepening of research in recent years,the intrinsic molecular mechanism of regulatory cell death(RCD)has gradually become clear.Researchers have found that the RCD mode plays a very important role in the occurrence and development of DCM.At present,the RCD modes involved in DCM mainly include apoptosis,necrotic apoptosis,pyroptosis,iron death,autophagy,and cuproptosis,and a certain correlation exists among them,which interact and regulate each other.This article provides an overview of the current research status on the mechanisms of the six RCD modes involved in DCM to provide a reference for future basic research and clinical applications.

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