1.PD-L1 Expression in Metastatic Lymph Nodes of NSCLC and Its Impact on First-line TKI or Chemotherapy Outcomes
Zhi XIE ; Zhiyi LÜ ; Danxia LU ; Shuilian ZHANG ; Weibang GUO ; Xue PAN ; Xuchao ZHANG ; Xuening YANG
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(2):269-282
ObjectiveTo investigate the heterogeneity of PD-L1 expression profiles between primary tumors and paired metastatic lymph nodes in advanced non-small cell lung cancer (NSCLC), and to determine the predictive value of key immune marker expression for the efficacy of first-line targeted therapy and chemotherapy. MethodsA retrospective analysis was conducted on 128 patients with histologically confirmed NSCLC and corresponding metastatic lymph nodes, who received first-line tyrosine kinase inhibitors (TKIs) or platinum-based doublet chemotherapy at Guangdong Provincial People's Hospital between April 2017 and February 2020. Immunohistochemistry (IHC) was employed to evaluate PD-L1 expression in primary tumors and metastatic lymph nodes. The Wilcoxon signed-rank test was performed to compare PD-L1 expression characteristics between primary tumors and metastatic lymph nodes. Kaplan-Meier survival curves were constructed, and the Log-rank test was used to compare differences between groups. ResultsAmong 28 paired cases, PD-L1 expression levels were numerically higher in metastatic lymph nodes than in primary NSCLC tumors (median:32.5 vs. 10.0), although the difference did not reach statistical significance (MD = 5.000, P = 0.083). Survival analysis revealed that in patients with driver gene-positive NSCLC, high PD-L1 expression (TPS ≥ 50%) in lymph nodes was significantly associated with shorter progression-free survival (PFS) following first-line TKI therapy [median PFS:4.0(TPS≥50%) vs. 8.9(1%≤TPS<50%) vs. 18.0 (TPS<1%) months, χ2=15.284, P<0.001]. Conversely, in patients with driver gene-negative NSCLC, high PD-L1 expression in lymph nodes was associated with longer PFS [median PFS:7.9 (TPS≥50%) vs. 3.0 (1%≤TPS<50%)months, χ2=8.436, P=0.004] and overall survival (OS) [median OS:28.8 (TPS≥50%) vs. 14.2 ( 1%≤TPS<50%) months, χ2=4.010, P=0.045] after first-line chemotherapy. ConclusionPD-L1 expression in metastatic lymph nodes is largely consistent with that in primary tumors of patients with advanced NSCLC. High PD-L1 expression in lymph nodes is associated with improved survival outcomes in driver gene-negative patients undergoing chemotherapy, whereas it portends a poor prognosis with TKI treatment in driver gene-positive patients. These findings support the application of PD-L1 expression levels in metastatic lymph nodes to guide personalized precision medicine strategies for advanced NSCLC.
2.Study of demonstrating main operative section of facial recess approach using double oblique multiplanar reconstruction on multislice CT
Zhihai LI ; Jingyao Lü ; Jianmin SHEN ; Guobing ZHANG ; Xi WEN ; Zhiyi CAI ; Yeqing LIN
Chinese Journal of Radiology 2012;46(1):13-18
Objective To explore the method of demonstrating main operative section of facial recess approach with multi-slice CT by using double oblique muttiplanar reconstruction.MethodsSimilarly as surgical procedure of facial recess approach,30 (60 eras) normal temporal bones in cadavers were reconstructed to observe main operative sections and anatomical marks.Main images of operative section of facial recess approach were reconstructed using double oblique multiplanar reconstruction on multislice CT.With the reference of operative anatomical marks,the ratios of visibility of anatomical marks on the transverse plane,coronal plane,sagittal plane and double oblique were calculated and compared.The degree,of which major anatomical landmarks were displayed on the same plane ( axial,coronal,sagittal,or doubleoblique sagittal plane),was classified using the following criteria: level 4: 100% of anatomical landmarks were presented in the same plane; level 3: 90% to 99% of anatomical landmarks were presented in the same plane; level 2: 80% to 89% of anatomical landmarks were presented in the same plane; level 1: 70% to 79% of anatomical landmarks were presented in the same plane ; level 0: < 70% of anatomical landmarks were presented in the same plane.Classification data were tested by chi-square test.Results Four key operative section were involved in facial recess approach,which were of oblique sagittal orientation.The central mark of the first key operative section was semicircular canal by using double oblique multi-planar reformation.On reconstructed images of the first key operative section,horizontal reference line was short process of incus,and the angle adjusting the reference line on the transverse plane was 22.15° ±5.22°.On the reconstructed images of the first key operative section,coronal reference line was tympanic segment of facial canal,and the angle adjusting the reference line on the coronal plane was 14.35° ± 4.02°.On the reconstructed images of the second key operative section,the central mark was fossa incudis,the horizontal reference line was short process of incus and the angle was 20.15° ± 5.52°,while the coronal reference line was tympanic segment of facial cana,and the angle was 13.15° ± 3.33°.On the reconstructed operative images of the third key section,the central mark was pyramidal eminence,the horizontal reference line was the horizontal portion of the facial nerve and the angle was 32.53° ±5.22°,while the coronal reference line was the tympanic segment of facial nerve,and the angle was 15.05° ± 4.43°.On the fourth reconstructed images of the key operative section,the central mark was the posterior border of round window,the horizontal reference line was the superior border of oval window,and the angle was 50.15° ± 8.02°,while the coronal reference line was the tympanic segment of facial nerve,and the angle was 15.25° ± 4.12°.For the four planes (double-oblique sagittal,axial,coronal,or sagittal plane),the results of the degree to which they could include the major anatomical landmarks in the same layer of the first section were: level 4 in 60 sides,level 2 in 12 sides and level 3 in 48 sides,level 2 in 15 sides and level 3 in 45 sides,level 3 in 10 sides and level 4 in 50 sides,respectively.The results of the second section were: level 4 in 60 sides,level 2 in 11 sides and level 3 in 49 sides,level 2 in 13 sides and level 3 in 47 sides,level 3 in 11 sides and level 4 in 49 sides,respectively.The results of the third section were: level 4 in 60 sides,level 2 in 10 sides and level 3 in 50 sides,level 2 in 11 sides and level 3 in 49 sides,level 3 in 9 sides and level 4 in 51 sides,respectively.The results of the fourth section were: level 4 in 60 sides,level 2 in 9 sides and level 3 in 51 sides,level 2 in 8 sides and level 3 in 52 sides,level 3 in 5 sides and level 4 in 55 sides,respectively.The four planes differed significantly in the degree to which they could include the major anatomical landmarks in the same layer ( x2 =123.3200,121.4231,122.4011,125.4213,all,P < 0.05 ).The visibility ratio of every section is 100% (60/60).Conclusion Double oblique multi-planar reformation is a new method to demonstrate landmarks of operative section of facial recess approach in one slice.The reconstructive images of operative section with double oblique multi-planer reconstruction may provide valuable information for operation.
3.The clinical characteristics of intra-acinar pulmonary artery inflammation and its effect on clinical parameters in smokers with normal lung function and patients with chronic obstructive pulmonary disease
Qifang LAO ; Xiaoning ZHONG ; Zhiyi HE ; Guangnan LIU ; Zili Lü ; Peng WAN
Chinese Journal of Internal Medicine 2011;50(10):839-844
ObjectiveTo study the pathological characteristics of intra-acinar pulmonary artery inflammation and its correlation with smoking index and disease progression in smokers with normal lung function and smokers with chronic obstructive pulmonary disease (COPD).MethodsPatients requiting lung resection for peripheral lung cancer were divided into group A (nonsmokers with normal lung function,n = 10), group B (smokers with normal lung function, n = 13), and group C (smokers with stable COPD,n = 10).The lung tissue far away from rumor were resected to compare the pathological changes of intraacinar pulmonary arteries and infiltration level of inflammatory cell in pulmonary non-muscularized arteries (NMA), pulmonary partially muscularized arteries (PMA) and muscularized arteries (MA) among the three groups.The correlation analysis was made among infiltration level, smoking index, percentage of predicted value of forced expiratory volume in one second (FEV,% Pred), six-minute-walk distance (6MWD) and BODE index.Results (1) Both group B and group C showed the intima and media thickness of MA was significantly higher, the lumen area of MA was narrower and the proportion of MA was higher, and collagenous fiber of MA adventitial proliferated and area increased in group C(P <0.05 or P <0.01).(2) In group B and group C, the percentage of the intra-acinar pulmonary arteries that contained leukocytes, T lymphocytes, CD8+ T lymphocytes and the number of these positive cells infiltrating the intraacinar pulmonary arteries were increased, especially an increased number of CD8+ T lymphocytes infiltrating in the arterial adventitia as compared with group A, moreover there were significant difference between group C and group B (P < 0.05 or P < 0.01).In group B and group C, the degree of these positive cellsinfiltrating NMA, PMA and MA presented a decreasing sequence (P < 0.05 or P < 0.01).Among the intima, media and adventitia of MA, the infiltration of these positive cells was the highest in the adventitia.Among group A, group B and group C, infiltration degree of CD4+ T lymphocyte, B lymphocyte, macrophage and neutrophil demonstrated no significant difference, also among NMA, PMA and MA (P > 0.05).(3)The number of leukocytes, T lymphocytes, CD8+T lymphocytes infiltrating MA showed a positive correlation with the thickness of MA (r =0.563,0.627,0.589 ,P <0.01 ,respectively) and smoking index (r =0.551,0.665, 0.600, P < 0.01, respectively), moreover the degree of these cells infiltrating MA demonstrated negative correlation with FEV1 % Pred (r = - 0.763, - 0.703, - 0.767, P < 0.01, respectively).Also infiltrating degree of T lymphocytes and CD8+ T lymphocytes was positively correlated with BODE(r = 0.390,0.476,P < 0.05, respectively). Furthermore the infiltrating degree of CD8+ T lymphocytes had negative correlation with 6MWD (r = - 0.356, P < 0.05).Conclusions(1) Pulmonary arterial inflammation appears in smokers with normal lung function and smokers with COPD patients.It involves in all types of intra-acinar pulmonary arteries especially NMA and infiltrates whole layer of MA with a characteristic of CDs+T lymphocytes infiltrating in the adventitia of intra-acinar pulmonary arteries. (2)Pulmonary inflammation is closely correlated to cigarette smoking and clinical parameters such as BODE index, FEV1%pred and 6MWD.It is one of the key factors affecting the progression of COPD.
4.Study of demonstrating main operative mark of transmastoid-epitympanum approach of the facial nerve using double oblique multi-planar reconstruction in multi-slice CT.
Zhihai LI ; Jingyao LÜ ; Baohong TAO ; Jianmin SHEN ; Guobing ZHANG ; Xi WEN ; Zhiyi CAI
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2011;25(19):865-868
OBJECTIVE:
To explore a method of demonstrating the facial nerve anatomical landmarks under transmastoid and epitympanum approach with multi-slice CT using double oblique multi-planar reconstruction (MPR).
METHOD:
Two temporal bone of a corpse were dissected, under transmastoid and epitympanum approach, to observe the anatomical landmarks of facial nerve. Based on that, the anatomical landmarks of facial nerve under transmastoid and epitympanum approach in 30 (60 ears) normal temporal bones of adult corpses were reconstructed using double oblique MPR in multi-slice CT. The achievement ratio was calculated and the differences among transverse plane, coronal plane, sagittal plane and double oblique were compared.
RESULT:
The different part of facial nerve, such as mastoid segment, tympanum segment, pyramid segment, geniculate ganglion and the outer labyrinthine segment could be exposed clearly with the main anatomical landmarks, such as horizontal semicircular canal, epitympanic recess and cochleariform process through transmastoid and epitympanum approach. The image of anatomical landmarks could be showed in the same sections by double oblique multi-planar reconstruction. The double oblique multi-planar reconstruction to show the landmarks of facial nerve displaying on the same imaging is better than transverse plane, coronal plane and sagittal plane. The achievement ratio of every section is 100%.
CONCLUSION
Double oblique MPR is a new method to demonstrate anatomical landmarks through transmastoid and epitympanum approach in one slice. Combined with the operative approach and purpose, the reconstructive images with double oblique MPR can provide valuable information for operation.
Adult
;
Ear, Middle
;
diagnostic imaging
;
surgery
;
Facial Nerve
;
diagnostic imaging
;
surgery
;
Female
;
Humans
;
Image Processing, Computer-Assisted
;
Male
;
Mastoid
;
diagnostic imaging
;
surgery
;
Tomography, Spiral Computed
5.The enhanced effects of liposome microbubble under ultrasound mediated gene transfection conditions
Zhiyi CHEN ; Mingxing XIE ; Xinfang WANG ; Qing Lü ; Shangwei DING
Chinese Journal of Ultrasonography 2009;18(1):62-66
Objective To study the transfeetion efficiency and safety of liposome microbubble(LM)on red fluorescent protein(RFP)in vitro and in vivo under ultrasound mediated gene transfection(USMGT)conditions.Methods Plasmids containing RFP were added to cultured Hela cells followed by ultrasound (US)exposure with LM.Different concentration of LM,US intensity and exposure time were optimized.Transfection efficiency was evaluated by fluorescent microscopy and FACS.Cell viability was verified by propidium iodide assay.In transplanted tumors in vivo study,LM and plasmid(P)were injected into the nude mice followed by US exposure(P+LM+US group).Nude mice undergoing plasmid injection alone(P group),plasmid injection and US exposure(P+US group)and plasmid and LM injection(P+LM group)were used as controls.Frozen section and histological examination were conducted and RFP expression was evaluated.Results LM and US exposure significantly increased transfeetion efficiency in cultured Hela cells (P< 0.01).Transfection efficiency was the most prominent under the condition of US intensity of 1.0 W/cm2 with 6%LM,duration 3 min.No apparent cell damage was found in the all groups.In transplanted tumors,strong RFP was seen in P+LM+US group.It was significantly higher than in any other groups(P<0.0 1).No tissue damage was seen histologically.Conclusions LM could enhance USMGT effectively without causing any apparently adverse effect in vitro and in vivo.This method would be a novel,effective,safe non-viral gene transfection method and provide an alternative to current clinical gene therapy.
6.The initial study of ultrasound-targeted microbubble destruction enhanced gene delivery in tumor xenografts accompanied with polyethylenimine
Zhiyi CHEN ; Mingxing XIE ; Xinfang WANG ; Qing Lü
Chinese Journal of Ultrasonography 2008;17(12):1082-1087
Objective To determine whether it could enhance gene delivery and tumor transfection in vivo by combination of ultrasound-targeted microbubble destruction(UTMD)with polyethylenimine(PEI)in tumor xenografts.Methods Two different reporter plasmid[lueiferase(pCMV-LUC)and red fluorescent protein(RFP)]were incubated with PEI to prepare cationic compound(PEI/DNA)in various nitrogen:phosphate ratios(N/P ratios,nmol of nitrogen in the PEI/nmol of phosphate in DNA).Formation of PEI/DNA complexes were confirmed by the gel retardation assay.Human cervical carcinoma(Hela)tumors were planted subcutaneously in both flanks of female nude mice.Tumor-bearing mice were administered by tail vein with PBS,plasmid,plasmid and Sono Vue microbubble,PEI/DNA and Sono Vue microbubble.One tumor was exposed to ultrasound irradiation (3 MHz,2 W/cm2,2 min exposure,duty cycle 20%),while the other served as control.The feasibility of targeted delivery and tissue specificity facilitated by UTMD and PEI was investigated.The mice were sacrificed 3 days after ultrasound exposure.Tissue specimens were viewed with microscopy to determine the presence of RFP expression.The efficiencies of luciferase transgene expression were determined.Histology analysis was detected.Results Electrophoresis experiment revealed that PEI was mixed with plasmid to condense DNA efficiently.The application of UTMD significantly increases the tissue transfection in vivo compared to plasmid alone.RFP expression was present in all sections of tumors that received ultrasound exposure but not in control tumors.Results of luciferase activity showed that the expression of luciferase was to be 14 times greater in ultrasound-exposed tumors(P<0.01).More importantly,the increase in transgene expresgion was related to UTMD with the presence of PEI dramatically.At least 10-fold increase of luciferase gene transfer was obtained in irradiated tumors compared to non-irradiated controls(P<0.01),111-fold increase compared to UTMD alone(P<0.01).There was not significantly gene expression in other organs or tissues regardless of US exposure(P>0.05).No tissue damage was seen histologically.Conclusions The combination of UTMD with PEI can enhance targeted delivery and expression of reporter gene to tumors at intravenous administration.It is a promising new and safe method for gene delivery in vivo.
7.The value of induced hypotension in nasal endoscopic surgery.
Zhiyi CAI ; Xiaofei WANG ; Baohong TAO ; Jingyao LÜ ; Ying WANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2008;22(8):349-351
OBJECTIVE:
To observe the value of induced hypotension in nasal endoscopic surgery with local anesthesia.
METHOD:
Sixty Patients were randomly divided into two groups. Group I : induced hypotension group; Group II: control group. MAP, HR, SaO2 amount of blood loss, clear visual field of operation and the operation time were observed and compared between two groups.
RESULT:
The difference of MAP, HR, SaO2 data between two groups showed no statistic difference with anatomical measurement (P >0.05). The difference of amount of blood loss, the operation time and clear visual field of operation between two groups was significant (P <0.05).
CONCLUSION
The induced hypotension with local anesthesia can produce time of operation and amount of blood loss decreased. It can safely applied to the in clinical practice.
Adolescent
;
Adult
;
Anesthesia, Local
;
Endoscopy
;
methods
;
Female
;
Humans
;
Hypotension, Controlled
;
Male
;
Middle Aged
;
Nose
;
surgery
;
Young Adult
8.Three dimensional reconstruction study of multi-slice helical CT imaging on optic canal area.
Zhihai LI ; Qixue GAO ; Zhiyi CAL ; Baohong TAO ; Jingyao LÜ
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2007;21(1):7-9
OBJECTIVE:
To investigate the accuracy and clinical application of multi-slice spiral CT imaging on optic canal area.
METHOD:
Forty intact specimens of human corpse head were tested with three dimensional reconstruction of multi-slice spiral CT imaging. The results of radiology and anatomy were compared on adjacent structures of optic canal interior wall and its developmental relationship with sphenoid sinus.
RESULT:
(1) The high spatial resolution of integrity could be obtained with dimensional processing technique. The anatomical structure of optic canal and its surrounding area could be demonstrated clearly. (2) With the technique of virtual endoscopy, the interior reconstruction of optic canal could demonstrate the inner topography of optic canal, the reconstruction image of which was identical to that of the control subjects. (3) There was no significant difference between the data of multi-slice spiral CT imaging and that of anatomy (P > 0.05).
CONCLUSION
Associated application of dimensional processing technique and virtual endoscopy, not only can the subtle structures of optic canal be demonstrated and measured, but also the detailed information on spatial relationships of optic canal area can be provided for operation.
Adult
;
Asian Continental Ancestry Group
;
Female
;
Humans
;
Imaging, Three-Dimensional
;
Male
;
Optic Nerve
;
anatomy & histology
;
diagnostic imaging
;
Tomography, Spiral Computed

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