1.Prognostic Value of Combined Serum ox-LDL,RC and NLR Tests for Clinical Prognosis in Patients with Intracranial Atherosclerotic Stenosis
Jianpu JIA ; Lixuan WANG ; Zeyu ZHAO ; Liran ZHANG ; Leguo ZHANG ; Ruixue XIA
Journal of Modern Laboratory Medicine 2025;40(2):104-108
Objective To explore the prognostic value of combined serum oxidized low-density lipoprotein(ox-LDL),remnant cholesterol(RC)and neutrophil-to-lymphocyte ratio(NLR)tests for clinical prognosis in patients with intracranial atherosclerotic stenosis(ICAS).Methods Patients with acute cerebral infarction were admitted to Cangzhou Central Hospital from June 2022 to December 2023 and diagnosed with ICAS by head MRI.A clinical diagnosis was selected(observation group,n=160).According to the modified Rankin scale(mRS)score,they were separated into a good prognosis group(mRS 0~2 points,n=52)and a poor prognosis group(mRS≥3 points,n=108).160 healthy volunteers who underwent physical examinations were used as a reference group.Magnetic particle immunochromatography was applied to detect serum ox-LDL levels.Clinical data of patients were collected,and the levels of RC and NLR were calculated.The Spearman method was used to analyze the correlation between serum ox-LDL,RC,NLR levels and mRS scores.Logistic regression was applied to analyze the factors influencing prognosis in ICAS patients.Receiver operating characteristic curve(ROC)was used to analyze the predictive value of serum ox-LDL,RC and NLR levels for the prognosis of ICAS patients.Results Compared with reference group,the serum levels of ox-LDL(53.65±8.35 U/L vs 33.23±6.42 U/L),RC(0.82±0.15 mmol/L vs 0.52±0.13 mmol/L)and NLR(2.84±0.38 vs 1.95±0.26)in observation group were obviously increased,and the differences were statistically significant(t=24.523,65.079,62.911,all P<0.05).The serum levels of ox-LDL(57.52±8.72 U/L),RC(0.84±0.14 mmol/L)and NLR(3.02±0.45)in the poor prognosis group were higher than those in the good prognosis group(45.62±6.63 U/L,0.79±0.12 mmol/L,2.48±0.36),and the differences were statistically significant(t=8.699,8.507,7.562,all P<0.05),and there were differences in TC,LDL-C,HDL-C levels and mRS scores between the two groups,and the differences were statistically significant(t=15.755~27.072,all P<0.05).The serum levels of ox-LDL,RC,NLR were positively correlated with mRS scores(r=0.612,0.623,0.653,all P<0.05).The levels of TC,LDL-C,HDL-C,ox-LDL,RC and NLR were all factors that affected the prognosis of ICAS(all P<0.05).The AUC of serum ox-LDL,RC and NLR for predicting prognosis in ICAS patients were 0.894(0.835~0.937),0.860(0.797~0.910)and 0.817(0.748~0.874),respectively.The combined AUC(95%CI)of the three was 0.965(0.923~0.987),the combination of the three was more valuable than predicting serum ox-LDL,RC and NLR alone(Z=3.030,3.969,4.839,all P<0.05).Conclusion The serum levels of ox-LDL,RC and NLR in ICAS patients have all increased and are positively correlated with mRs scores.The three have predictive value for the prognosis of ICAS patients,and the combined detection of the three has higher clinical value.
2.Adult-onset Still's disease with dermatopathic lymphadenitis complicated with hemophagocytic syndrome:A case report and literature review
Yuxin LIU ; Lixuan WANG ; Min ZHAO ; Peiyuan CHENG ; Ke WANG
Journal of Jilin University(Medicine Edition) 2025;51(3):790-796
Adult-onset Still's disease(AOSD)is a rare autoinflammatory disease characterized by fever,rash,arthritis,liver,spleen and lymph node enlargement,increased total number of peripheral white blood cells and neutrophil ratio.This paper reported a case of AOSD with dermal lymphadenitis(DL)complicated with hemophagocytic syndrome(HPS),in order to improve the clinicians'understanding for this complicated complication.The patient was a 48-year-old female who was admitted to the hospital with the complant of"intermittent fever with rash for 15 d".After 10 d of active anti-infection treatment,the symptoms were not improved,and there were new large congestive edematous erythema on the face and trunk,muscle pain in limbs and joints,and spleen enlargement.Laboratory tests showed increased white blood cell count,significantly decreased platelet count,hypofibrinogenemia,elevated serum ferritin,and elevated soluble interleukin-2 receptor sCD25;DL was pathologically diagnosed by axillary lymph node biopsy.After excluding other diseases,the diagnosis was confirmed as AOSD with DL complicated with HPS.After diagnosis of HPS,the patient was treated with hemophagocytic lymphohistiocytosis(HLH)-1994 regimen combined with rucotinib for 6 weeks,and the symptoms were improved;the patrent was discharged.The diagnosis of AOSD is particularly complex when complicated with the complications such as HPS,which requires carefully differential diagnosis,especially to exclude lymphoma.The cases of AOSD with DL are rare,and its etiology and pathogenesis need further study;early diagnosis and multidisciplinary collaboration are essential to improve the patient's prognosis.
3.Effect of decentration and tilt on in vitro optical quality of intraocular lenses with different focus designs
Ruolin PAN ; Xuan LIAO ; Changjun LAN ; Lixuan XIE ; Qingqing TAN ; Suyun QIN ; Huan HUANG ; Yan WANG
Chinese Journal of Experimental Ophthalmology 2025;43(3):211-218
Objective:To observe the effect of different degrees of decentration and tilt on the optical quality of the intraocular lenses (IOLs) with different focus designs.Methods:The UV 3300 PC UV-visible spectrophotometer was employed to measure the spectral transmittance of the monofocal IOL CT ASPHINA 509M (509M), bifocal IOL AT LISA 809M (809M), and trifocal IOL AT LISA Tri 839MP (839MP) within Zeiss MICS platform with a refractive power of + 20 D. The modulation transfer function (MTF) values at a spatial frequency of 50 lp/mm along with MTF curves and United States Air Force (USAF) resolution test charts for each IOL at the focal point were measured at apertures of 3.0 mm and 4.5 mm using the in vitro optical quality testing system OptiSpheric IOL R&D under centered, decentered (0.3, 0.5, 0.7, 0.9 and 1.1 mm) and tilted (3°, 5°, 7°, 9° and 11°) conditions. Results:All three IOLs filtrated the ultraviolet (UV) spectrum below 400 nm.When each IOL was in the centered position, at the 3.0 mm aperture, the MTF values were 0.772 at the far focus of the monofocal IOL 509M, 0.467 and 0.282 at the far and near focus of the bifocal IOL 809M, and 0.416, 0.147, and 0.229 at the far, intermediate, and near focus of the trifocal IOL 839MP, respectively.Whereas at the 4.5 mm aperture, the monofocal IOL 509M MTF value at the far focus was 0.664, the bifocal IOL 809M MTF values at the far and near focus were 0.506 and 0.264, and the trifocal IOL 839MP MTF values at the far, intermediate, and near focus were 0.392, 0.107, and 0.210, respectively.Among the three centered IOLs, the 509M demonstrated the highest MTF value at the far focus, followed by the 809M and then the 839MP; at the near focus, the MTF value of the 809M surpassed that of the 839MP.For decentration and tilt, the difference in MTF values of the three IOLs at the far and near focus was consistent with the differences observed when they were centered.At the same degree of decentration and tilt, all three IOLs exhibited superior optical quality at the 3.0 mm aperture compared to the 4.5 mm aperture.The optical quality of all three IOLs exhibited an overall decline as decentration and tilt increased.All three IOLs demonstrated a decrease in optical quality at the decentration of 0.3 mm or the tilt of 5°.Conclusions:The IOLs within the Zeiss MICS platform design exhibits identical spectral transmittance and UV filtering properties.Among the three IOLs, when centered, the 509M, the 839MP, and the 809M exhibit superior optical quality at the far, intermediate, and near focal points, respectively.Under decentered and tilted conditions, the 509M and the 809M demonstrate better resistance against decentration and tilt, respectively, at both far and near focuses.Additionally, all three IOLs demonstrate better optical quality at smaller apertures, given equivalent degrees of decentration or tilt.However, the optical quality at each focal point of the three IOLs decreases compared to the centered position when subjected to a decentration of 0.3 mm or a tilt of 5°.
4.Effect of decentration and tilt on in vitro optical quality of intraocular lenses with different focus designs
Ruolin PAN ; Xuan LIAO ; Changjun LAN ; Lixuan XIE ; Qingqing TAN ; Suyun QIN ; Huan HUANG ; Yan WANG
Chinese Journal of Experimental Ophthalmology 2025;43(3):211-218
Objective:To observe the effect of different degrees of decentration and tilt on the optical quality of the intraocular lenses (IOLs) with different focus designs.Methods:The UV 3300 PC UV-visible spectrophotometer was employed to measure the spectral transmittance of the monofocal IOL CT ASPHINA 509M (509M), bifocal IOL AT LISA 809M (809M), and trifocal IOL AT LISA Tri 839MP (839MP) within Zeiss MICS platform with a refractive power of + 20 D. The modulation transfer function (MTF) values at a spatial frequency of 50 lp/mm along with MTF curves and United States Air Force (USAF) resolution test charts for each IOL at the focal point were measured at apertures of 3.0 mm and 4.5 mm using the in vitro optical quality testing system OptiSpheric IOL R&D under centered, decentered (0.3, 0.5, 0.7, 0.9 and 1.1 mm) and tilted (3°, 5°, 7°, 9° and 11°) conditions. Results:All three IOLs filtrated the ultraviolet (UV) spectrum below 400 nm.When each IOL was in the centered position, at the 3.0 mm aperture, the MTF values were 0.772 at the far focus of the monofocal IOL 509M, 0.467 and 0.282 at the far and near focus of the bifocal IOL 809M, and 0.416, 0.147, and 0.229 at the far, intermediate, and near focus of the trifocal IOL 839MP, respectively.Whereas at the 4.5 mm aperture, the monofocal IOL 509M MTF value at the far focus was 0.664, the bifocal IOL 809M MTF values at the far and near focus were 0.506 and 0.264, and the trifocal IOL 839MP MTF values at the far, intermediate, and near focus were 0.392, 0.107, and 0.210, respectively.Among the three centered IOLs, the 509M demonstrated the highest MTF value at the far focus, followed by the 809M and then the 839MP; at the near focus, the MTF value of the 809M surpassed that of the 839MP.For decentration and tilt, the difference in MTF values of the three IOLs at the far and near focus was consistent with the differences observed when they were centered.At the same degree of decentration and tilt, all three IOLs exhibited superior optical quality at the 3.0 mm aperture compared to the 4.5 mm aperture.The optical quality of all three IOLs exhibited an overall decline as decentration and tilt increased.All three IOLs demonstrated a decrease in optical quality at the decentration of 0.3 mm or the tilt of 5°.Conclusions:The IOLs within the Zeiss MICS platform design exhibits identical spectral transmittance and UV filtering properties.Among the three IOLs, when centered, the 509M, the 839MP, and the 809M exhibit superior optical quality at the far, intermediate, and near focal points, respectively.Under decentered and tilted conditions, the 509M and the 809M demonstrate better resistance against decentration and tilt, respectively, at both far and near focuses.Additionally, all three IOLs demonstrate better optical quality at smaller apertures, given equivalent degrees of decentration or tilt.However, the optical quality at each focal point of the three IOLs decreases compared to the centered position when subjected to a decentration of 0.3 mm or a tilt of 5°.
5.Prognostic Value of Combined Serum ox-LDL,RC and NLR Tests for Clinical Prognosis in Patients with Intracranial Atherosclerotic Stenosis
Jianpu JIA ; Lixuan WANG ; Zeyu ZHAO ; Liran ZHANG ; Leguo ZHANG ; Ruixue XIA
Journal of Modern Laboratory Medicine 2025;40(2):104-108
Objective To explore the prognostic value of combined serum oxidized low-density lipoprotein(ox-LDL),remnant cholesterol(RC)and neutrophil-to-lymphocyte ratio(NLR)tests for clinical prognosis in patients with intracranial atherosclerotic stenosis(ICAS).Methods Patients with acute cerebral infarction were admitted to Cangzhou Central Hospital from June 2022 to December 2023 and diagnosed with ICAS by head MRI.A clinical diagnosis was selected(observation group,n=160).According to the modified Rankin scale(mRS)score,they were separated into a good prognosis group(mRS 0~2 points,n=52)and a poor prognosis group(mRS≥3 points,n=108).160 healthy volunteers who underwent physical examinations were used as a reference group.Magnetic particle immunochromatography was applied to detect serum ox-LDL levels.Clinical data of patients were collected,and the levels of RC and NLR were calculated.The Spearman method was used to analyze the correlation between serum ox-LDL,RC,NLR levels and mRS scores.Logistic regression was applied to analyze the factors influencing prognosis in ICAS patients.Receiver operating characteristic curve(ROC)was used to analyze the predictive value of serum ox-LDL,RC and NLR levels for the prognosis of ICAS patients.Results Compared with reference group,the serum levels of ox-LDL(53.65±8.35 U/L vs 33.23±6.42 U/L),RC(0.82±0.15 mmol/L vs 0.52±0.13 mmol/L)and NLR(2.84±0.38 vs 1.95±0.26)in observation group were obviously increased,and the differences were statistically significant(t=24.523,65.079,62.911,all P<0.05).The serum levels of ox-LDL(57.52±8.72 U/L),RC(0.84±0.14 mmol/L)and NLR(3.02±0.45)in the poor prognosis group were higher than those in the good prognosis group(45.62±6.63 U/L,0.79±0.12 mmol/L,2.48±0.36),and the differences were statistically significant(t=8.699,8.507,7.562,all P<0.05),and there were differences in TC,LDL-C,HDL-C levels and mRS scores between the two groups,and the differences were statistically significant(t=15.755~27.072,all P<0.05).The serum levels of ox-LDL,RC,NLR were positively correlated with mRS scores(r=0.612,0.623,0.653,all P<0.05).The levels of TC,LDL-C,HDL-C,ox-LDL,RC and NLR were all factors that affected the prognosis of ICAS(all P<0.05).The AUC of serum ox-LDL,RC and NLR for predicting prognosis in ICAS patients were 0.894(0.835~0.937),0.860(0.797~0.910)and 0.817(0.748~0.874),respectively.The combined AUC(95%CI)of the three was 0.965(0.923~0.987),the combination of the three was more valuable than predicting serum ox-LDL,RC and NLR alone(Z=3.030,3.969,4.839,all P<0.05).Conclusion The serum levels of ox-LDL,RC and NLR in ICAS patients have all increased and are positively correlated with mRs scores.The three have predictive value for the prognosis of ICAS patients,and the combined detection of the three has higher clinical value.
6.Causal Relationship Between Gut Microbiota and Duodenal Ulcer:A Two-sample Mendelian Randomization Study
Yaqi HOU ; Yuan LI ; Lixuan YAN ; Wanli GONG ; Yang WANG ; Xuechun LU ; Peifeng HE ; Qi YU
Chinese Journal of Gastroenterology 2024;29(5):276-282
Background:The diversity and function of gut microbiota have been regarded as crucial factors affecting human health.With the advances in genetics and epidemiology,especially the application of Mendelian randomization analysis,a novel perspective has been provided for profoundly uncovering the causal relationship between gut microbiota and duodenal ulcer.Aims:To investigate the causal relationship between gut microbiota and duodenal ulcer through two-sample Mendelian randomization analysis.Methods:Genetic variation samples of the gut microbiota were screened from the MiBioGen database.Genetic loci related to duodenal ulcer were selected as instrumental variables from genome-wide association study.The inverse-variance weighted method,weighted median method,and MR-Egger regression analysis were used to assess the causal relationship between gut microbiota and duodenal ulcer.Tests for heterogeneity and horizontal pleiotropy were conducted to ensure the stability of the results.Results:Bacteroides(OR=0.998,95%CI:0.996-1.000,P=0.014),Prevotella_7(OR=0.999,95%CI:0.998-1.000,P=0.043)and Terrisporobacter(OR=0.998,95%CI:0.997-1.000,P=0.029)exhibited negative causal relationship with duodenal ulcer,while Bifidobacterium(OR=1.001,95%CI:1.000-1.003,P=0.046),Lachnoclostridium(OR=1.002,95%CI:1.001-1.004,P=0.007)and Olsenella(OR=1.001,95%CI:1.000-1.002,P=0.018)presented positive causal relationship with duodenal ulcer.The sensitivity analysis indicated that the influences of heterogeneity and horizontal pleiotropy on the causal relationship could be excluded.Conclusions:The two-sample Mendelian randomization analysis revealed that Bacteroides,Prevotella_7 and Terrisporobacter were protective factors for duodenal ulcer,while Bifidobacterium,Lachnoclostridium and Olsenella were risk factors.
7.Evaluation of optical performance of aspherical intraocular lens in vitro by optical bench
Lixuan XIE ; Xuan LIAO ; Changjun LAN ; Qingqing TAN ; Ruolin PAN ; Yuling TANG ; Suyun QIN ; Yan WANG
Chinese Journal of Experimental Ophthalmology 2024;42(3):240-247
Objective:To evaluate the optical performance of two aspheric intraocular lenses (IOL) AcrySof IQ SN60WF and Proming A1-UV with identical negative spherical aberration values, using the optical bench OptiSpheric IOL R&D through an in vitro study. Methods:The optical performance of + 20.0 D blue-light filtering SN60WF and monofocal high-order aspheric non blue-light filtering A1-UV IOL was evaluated through cornea models with the spherical aberration of 0 μm (ISO-1) and + 0.28 μm (ISO-2) under apertures of 3.0 mm and 4.5 mm via the optical bench OptiSpheric IOL R&D.The modulation transfer function (MTF) and USAF 1951 resolution test chart were employed to measure the IOL with centering, decentration of 0.3, 0.5, 0.7, 0.9 and 1.1 mm, as well as tilt of 3°, 5°, 7°, 9° and 11°.The spectral transmittance of IOL was measured with the UV-3300 UV-VIS spectrophotometer.Results:Compared with the A1-UV IOL, the spectral transmittance of SN60WF for blue light with wavelengths of 400-500 nm was significantly reduced, which effectively reduced the passage of blue light.At an aperture of 3.0 mm, the MTF values at 100 lp/mm spatial frequency for the centered SN60WF and A1-UV were 0.576 and 0.598 under ISO-1 corneal measurement conditions, 0.564 and 0.563 under ISO-2 conditions.At an aperture of 4.5 mm, the MTF values were 0.238 and 0.404 under ISO-1 corneal measurement conditions, and 0.438 and 0.339 under ISO-2 conditions.The MTF values of A1-UV and SN60WF at 3.0 mm aperture and 100 lp/mm spatial frequency under ISO-1 corneal measurement conditions were larger than those under ISO-2 corneal measurement conditions.Under ISO-1 corneal measurement conditions with a 3.0 mm aperture, A1-UV had a better optical quality compared to SN60WF, whereas under ISO-2 corneal measurement conditions, the optical quality of both IOLs was similar.Under the 3.0 mm aperture, the MTF values of SN60WF and A1-UV at a decentration of 0.3 mm and 100 lp/mm spatial frequency were 0.414 and 0.571 under ISO-1 corneal measurement conditions, 0.438 and 0.512 under ISO-2 corneal measurement conditions, respectively.The MTF values of SN60WF and A1-UV at a tilt of 3° were 0.522 and 0.597 under ISO-1 corneal measurement conditions, and 0.532 and 0.531 under ISO-2 corneal measurement conditions.The MTF values and USAF resolution test chart of A1-UV had no significant change between the two corneal measurement conditions.When subjected to equal degrees of decentration or tilting, except for the ISO-1 corneal measurement conditions at a 4.5 mm aperture, the MTF values of A1-UV showed a gradual decline across various spatial frequencies compared to SN60WF.With the increase in aperture size, the impact of IOL decentration or tilting on MTF values and USAF 1951 resolution test chart became more notable for A1-UV relative to SN60WF.Conclusions:The SN60WF IOL effectively filters blue light within the wavelength range of 400-500 nm.However, when both IOL experience decentration greater than 0.3 mm or tilting beyond 3°, the optical quality of the IOL will decline.A1-UV has a distinct advantage over SN60WF in terms of resistance to both decentration and tilting-induced optical performance degradation in vitro.
8.Integrative single-cell and bulk transcriptomes analyses reveals heterogeneity of serine-glycine-one-carbon metabolism with distinct prognoses and therapeutic vulnerabilities in HNSCC
Wang LIXUAN ; Yang RONGCHUN ; Kong YUE ; Zhou JING ; Chen YINGYAO ; Li RUI ; Chen CHUWEN ; Tang XINRAN ; Chen XIAOBING ; Xia JUAN ; Chen XIJUAN ; Cheng BIN ; Ren XIANYUE
International Journal of Oral Science 2024;16(4):711-727
Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment(TME),which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma(HNSCC)patients.This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology.The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing(scRNA-seq)profiles and validated through bulk transcriptomes.Serine-glycine-one-carbon(SGOC)metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients.A 4-SGOC gene prognostic signature,constructed by LASSO-COX regression analysis,demonstrated good predictive performance for overall survival and therapeutic responses.Patients in the low-risk group exhibited greater infiltration of exhausted CD8+T cells,and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy.Conversely,high-risk patients exhibited characteristics of cold tumors,with enhanced IMPDH1-mediated purine biosynthesis,resulting in poor responses to current therapies.IMPDH1 emerged as a potential therapeutic metabolic target.Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress.Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.
9.Causal Relationship Between Gut Microbiota and Duodenal Ulcer:A Two-sample Mendelian Randomization Study
Yaqi HOU ; Yuan LI ; Lixuan YAN ; Wanli GONG ; Yang WANG ; Xuechun LU ; Peifeng HE ; Qi YU
Chinese Journal of Gastroenterology 2024;29(5):276-282
Background:The diversity and function of gut microbiota have been regarded as crucial factors affecting human health.With the advances in genetics and epidemiology,especially the application of Mendelian randomization analysis,a novel perspective has been provided for profoundly uncovering the causal relationship between gut microbiota and duodenal ulcer.Aims:To investigate the causal relationship between gut microbiota and duodenal ulcer through two-sample Mendelian randomization analysis.Methods:Genetic variation samples of the gut microbiota were screened from the MiBioGen database.Genetic loci related to duodenal ulcer were selected as instrumental variables from genome-wide association study.The inverse-variance weighted method,weighted median method,and MR-Egger regression analysis were used to assess the causal relationship between gut microbiota and duodenal ulcer.Tests for heterogeneity and horizontal pleiotropy were conducted to ensure the stability of the results.Results:Bacteroides(OR=0.998,95%CI:0.996-1.000,P=0.014),Prevotella_7(OR=0.999,95%CI:0.998-1.000,P=0.043)and Terrisporobacter(OR=0.998,95%CI:0.997-1.000,P=0.029)exhibited negative causal relationship with duodenal ulcer,while Bifidobacterium(OR=1.001,95%CI:1.000-1.003,P=0.046),Lachnoclostridium(OR=1.002,95%CI:1.001-1.004,P=0.007)and Olsenella(OR=1.001,95%CI:1.000-1.002,P=0.018)presented positive causal relationship with duodenal ulcer.The sensitivity analysis indicated that the influences of heterogeneity and horizontal pleiotropy on the causal relationship could be excluded.Conclusions:The two-sample Mendelian randomization analysis revealed that Bacteroides,Prevotella_7 and Terrisporobacter were protective factors for duodenal ulcer,while Bifidobacterium,Lachnoclostridium and Olsenella were risk factors.
10.Integrative single-cell and bulk transcriptomes analyses reveals heterogeneity of serine-glycine-one-carbon metabolism with distinct prognoses and therapeutic vulnerabilities in HNSCC
Wang LIXUAN ; Yang RONGCHUN ; Kong YUE ; Zhou JING ; Chen YINGYAO ; Li RUI ; Chen CHUWEN ; Tang XINRAN ; Chen XIAOBING ; Xia JUAN ; Chen XIJUAN ; Cheng BIN ; Ren XIANYUE
International Journal of Oral Science 2024;16(4):711-727
Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment(TME),which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma(HNSCC)patients.This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology.The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing(scRNA-seq)profiles and validated through bulk transcriptomes.Serine-glycine-one-carbon(SGOC)metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients.A 4-SGOC gene prognostic signature,constructed by LASSO-COX regression analysis,demonstrated good predictive performance for overall survival and therapeutic responses.Patients in the low-risk group exhibited greater infiltration of exhausted CD8+T cells,and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy.Conversely,high-risk patients exhibited characteristics of cold tumors,with enhanced IMPDH1-mediated purine biosynthesis,resulting in poor responses to current therapies.IMPDH1 emerged as a potential therapeutic metabolic target.Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress.Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

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