1.The application strategies of non-uniform sampling in the structure elucidation of small molecule compounds—an instantiation using fuziline
Li-li ZHANG ; Ke ZHANG ; Jie LIU ; Chun-wang MENG ; Rui FENG ; Liang XIONG
Acta Pharmaceutica Sinica 2025;60(1):218-224
Two-dimensional nuclear magnetic resonance (2D NMR) is a widely used technique for structural analysis of small molecular compounds. It can obtain information about the hydrogen-hydrogen correlation, hydrogen-carbon single bond correlation, hydrogen-carbon remote correlation, and hydrogen-hydrogen spatial arrangement of compounds. Thus, 2D NMR has an irreplaceable role in the structure elucidation of small molecular products. However, the sample amount of trace components in phytochemical research is very low, and the traditional sampling method (uniform sampling) has problems of poor spectral quality and too long measure time. Increasing the number of scans results in several hours of the acquisition time for a single two-dimensional spectrum, which in turn causes strain on the NMR machine. The non-uniform sampling (NUS) technique can shorten the acquisition time to a large extent and not affect the quality of 2D NMR data, which greatly improves the efficiency of 2D NMR acquisition. In this paper, fuziline, a small molecular compound in the lateral roots of
2.Effects of Tripterygium wilfordii multiglycoside on renal injury in rats with diabetic nephropathy
Chong ZHANG ; Chundong SONG ; Mo WANG ; Shuang LIANG ; Xiaoxiao GUO ; Hanhan ZHANG ; Peijia LI ; Ke SONG ; Chenchen CHEN
China Pharmacy 2025;36(7):815-819
OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside (TWM) on renal injury in diabetic nephropathy (DN) rats through tumor protein p53/microRNA-214 (miR-214)/UNC-51-like kinase 1 (ULK1) axis. METHODS Male SD rats were randomly divided into normal group (n=6) and modeling group (n=28); the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group, valsartan group [8.33 mg/(kg·d)] and TWM group[6.25 mg/(kg·d)], with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline, once a day, for 6 consecutive weeks. After the last medication, liver and renal function indexes [24 h urinary total protein (24 h-UTP), blood urea nitrogen (BUN), serum creatinine (SCr), albumin (ALB), alanine transaminase (ALT)], blood lipid indexes (triglycerides, total cholesterol) and blood glucose index (fasting blood glucose) in urine/blood sample of rats were detected in each group. Renal pathologic change was observed, protein and mRNA expressions of p53, ULK1, Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3), and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group, the renal tubular epithelium of rats in the model group showed obvious edema, cell swelling, accompanied by lymphocyte infiltration; the levels of 24h-UTP, BUN, SCr, ALT and glycolipid indexes, the expressions of p53 protein and mRNA, as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated, while ALB level, LC3-Ⅱ/LC3-Ⅰ, the expressions of LC3 mRNA, the expressions of ULK1, Beclin-1 protein and mRNA were significantly decreased or down-regulated (P<0.01). Compared with the model group, the histopathological damage of the kidney in rats was improved in administration groups; the levels of 24 h-UTP, BUN, SCr, ALT and glycolipid indexes, the expressions of p53 protein and mRNA, as well as the expression of miR-214 were all significantly decreased or down-regulated, while ALB level, LC3-Ⅱ/LC3-Ⅰ, the expressions of LC3 mRNA, the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated (P<0.01). CONCLUSIONS TG can alleviate renal damage in DN rats, and improve their liver and renal function, as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.
3.Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics
Yu-long CHEN ; You ZHAI ; Xiao-yan WANG ; Wei-xia LI ; Hui ZHANG ; Ya-li WU ; Liu-qing YANG ; Xiao-fei CHEN ; Shu-qi ZHANG ; Lu NIU ; Ke-ran FENG ; Kun LI ; Jin-fa TANG ; Ming-liang ZHANG
Acta Pharmaceutica Sinica 2024;59(2):382-394
Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and
4.Finite element and biomechanical analysis of different implants in repair for unilateral unstable pelvic posterior ring injury
Cheng LIANG ; Linqi ZHANG ; Guan WANG ; Wen LI ; Ke DUAN ; Zhong LI ; Xiaobo LU ; Naiqiang ZHUO
Chinese Journal of Tissue Engineering Research 2024;28(9):1336-1341
BACKGROUND:The stability of the pelvis is mainly determined by the posterior pelvic ring and the sacroiliac joint.The posterior pelvic ring injury and the dislocation of the sacroiliac joint caused by high energy impacts such as car accidents increase year by year.Surgical treatment is the best method,and there are many kinds of endophytorepair methods in clinical practice,but which treatment method has the best biomechanical properties is still controversial. OBJECTIVE:To compare the biomechanical properties of three kinds of internal implants:anterior double plates,posterior bridging plate and tension nail in the repair of unilateral unstable pelvic posterior ring injury,to provide a reference for the clinical treatment and development of a new pelvic tension screw. METHODS:(1)Finite element simulation:Mimics,Wrap and SolidWorks were used to establish normal pelvic model,unilateral injured pelvis model,and three kinds of internal implant repaired models(anterior double plates,posterior bridging plate and tension nail).Ansys was used to analyze the stress and deformation of the models.(2)Biomechanical test:A total of 15 intact pelvic specimens were randomly grouped into five groups,normal pelvic model,unilateral injured pelvis model,anterior double plates,posterior bridging plate and tension nail groups.The mechanical test was performed using an Instron E10000 testing machine. RESULTS AND CONCLUSION:(1)Simulation:In the normal pelvic model,the average displacement of the sacrum was 0.174 mm,and the maximum stress of the sacral iliac bone was 10.51 MPa,and the stress distribution was uniform.The mean sacral displacement of the unilateral injured pelvis model was 0.267 mm,and the stress concentration of the model was obvious.The mean displacement of the sacrum in the three repaired models was close to that in the normal pelvic model,and the stress distribution of the sacral iliac bone in the tension nail repaired model was uniform.(2)Mechanical test:The stiffness of the normal pelvic model was(226.38±4.18)N/mm,and that of the unilateral unstable pelvic model was the smallest(130.02±2.19)N/mm.The deviation of the normal pelvic model stiffness and the three repaired models'stiffness were all within(±10%),and the repair effect was obvious.(3)The simulation results were in agreement with the experimental results.(4)The biomechanics of the tension nail repaired model was the most similar to that of the normal pelvis,and this method was the best.The repairing stiffness of the anterior double plate was too large,and the stress shielding effect was more significant.The posterior bridging plate repair could not solve the compensatory effect of the normal side soft tissue and had defects.This study provides an optimal basis for clinical surgery.(5)The new type of pelvic tension nail should be improved from the point of view of the tension nail to retain the good biomechanical properties of the tension nail,while adding other advantages,such as being used for the osteoporotic pelvis.
5.Propulsion deficits in hemiplegic gait of stroke patients
Liang ZHI ; Yulong WANG ; Qingfang ZHANG ; Yaqing HONG ; Meihua KE ; Quanquan LIU ; Jianjun LONG
Chinese Journal of Tissue Engineering Research 2024;28(35):5709-5715
BACKGROUND:The abnormal gait of stroke patients seriously affects their propulsive force during walking,which subsequently reduces their walking speed,walking distance,and stability,increases their risk of falls,and seriously affects their quality of life. OBJECTIVE:To review the relevant research on propulsive force deficits in stroke patients with hemiplegia,to summarize the understanding of existing researchers on propulsive force deficits,to analyze the relationship between propulsive force and gait,and finally to explain and compare the latest rehabilitation technologies used to improve propulsive force deficits,providing reference for clinical treatment. METHODS:Relevant literature was retrieved from WanFang,CNKI,PubMed,and Web of Science Core Collection through computer search.The Chinese and English search terms were"propulsive force OR propulsive,stroke OR cerebral infarction OR hemiplegia,walk* OR gait."The search time limit was from 2003 to 2023,and 71 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Training targeting the hip and ankle joints may be more effective for patients'walking function,especially training with the application of flexible exoskeleton robots,but more sufficient evidence is still needed to use propulsion as a prognostic indicator of walking function in stroke patients.Biomechanical variables related to propulsive force include:the hip joint extension angle at terminal stance,ankle joint dorsiflexion torque,and knee joint extension.Damage to the corticospinal tract,cerebellar-cortical pathways,and the reticulospinal tract in hemiplegic patients are associated with reduced propulsive force and gait asymmetry.Propulsive force is crucial for the stability of healthy gait,and a decrease in propulsive force is unfavorable for gait stability.Gait symmetry is correlated with propulsive force,stride length symmetry,trunk displacement,and lower limb swing ability,with propulsive force being a key factor.Propulsive force can serve as a quantitative indicator for assessing the gait of hemiplegic patients,and evaluation of gait using propulsive force is beneficial for the long-term development of walking ability.Main rehabilitation techniques for improving propulsive force include:lower limb exoskeleton robot walking training,treadmill training combined with functional electrical stimulation,adaptive speed treadmill training,biofeedback technology,and whole-body vibration training.Among them,whole-body vibration training and biofeedback technology are more effective.The specific contributions and mechanisms of the hip,knee,and ankle joints in improving propulsive force are still controversial,but it is expected that the contributions of the hip and ankle joints are greater.Focusing on the improvement of propulsive force as a rehabilitation goal may yield more sustainable advancements in walking function.However,several current challenges persist in this field:understanding the neurobiological basis of propulsive force deficits in stroke patients,assessing the long-term efficacy of current rehabilitation techniques for enhancing propulsive force,and determining the most suitable patient populations for the application of major rehabilitation techniques aiming at improving propulsive force.These areas require further exploration by subsequent researchers.
6.Study on the antidepressant mechanism of ginseng-fragrant solomonseal rhizome couplet medicines on inhibiting the activation of inflammasomes NLRP1,NLRC4,and AIM2,and regulating the expression of inflammatory cytokines
Huayu ZHANG ; Jialu CAO ; Bingyuan ZHENG ; Qian LIU ; Ke LIANG ; Tie QIAO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(7):939-947
Objective To observe the effect of Renshen(ginseng)-Yuzhu(fragrant solomonseal rhizome)on inflammatory factors and inflammasomes in depression rats,and to explore the antidepressant mechanism of Renshen-Yuzhu.Methods Fifty male SD rats were divided into the blank group,model group,fluoxetine group(2.1 mg/kg),Renshen-Yuzhu low-dose group(1.89 g/kg),and Renshen-Yuzhu high-dose group(5.67 g/kg),with ten rats in each group.Except for the blank group,the rats in the other groups were treated with chronic unpredictable mild stress to establish a depression rat model.On the second day after the end of modeling,the rats in each group were given the corresponding drugs once daily for 14 days.After modeling and dosing,body weight,forced swimming immobility time,and sucrose preference rate were measured.After dosing,hematoxylin-eosin staining was used to detect neuronal damage in the cerebral cortex,enzyme-linked immunosorbent assay was used to detect the contents of interleukin-4(IL-4),interleukin-23(IL-23),and interleukin-27(IL-27)in cortex,real-time PCR was used to detect the mRNA expression of interleukin-24(IL-24)in cortex,and the protein expressions of nucleotide-binding oligomerization domain-like receptor protein 1(NLRP1),absent in melanoma 2(AIM2),and nucleotide-binding oligomerization domain-like receptor protein 4(NLRC4)were detected by Western blotting.Results After dosing,compared with the blank group,the body weight of the model group decreased,the sucrose preference rate decreased,the swimming immobility time was prolonged,the neuronal tissue in cortex was destroyed,the content of IL-4 in cortex decreased,the contents of IL-23 and IL-27 in cortex increased,and the protein expressions of NLRP1,AIM2 and NLRC4 in cortex increased(P<0.01).Compared with the model group,the body weight of rats in each administration group increased,the sucrose preference rate increased,the swimming immobility time was shortened,the damage of neuronal tissues in cortex improved,the content of IL-4 in cortex increased,the contents of IL-23 and IL-27 in cortex decreased,and the protein expressions of NLRP 1,AIM2 and NLRC4 in cortex decreased(P<0.05).Conclusion Renshen-Yuzhu couplet medicines can improve the depressive-like behavior and exert antidepressant effect in chronic stress rats,and its mechanism may be related to the inhibition of NLRP 1,NLRC4,AIM2 inflammasome activation and its mediated inflammatory response in cortex,reducing pro-inflammatory cytokines,and increasing the level of antiinflammatory cytokines.
7.Effects of vecuronium bromide down-regulation of lncRNA FGD5-AS1 on the proliferation and apoptosis of gastric cancer cell HGC-27
Bin FU ; Ke ZHANG ; Xing LIU ; Chuan-Xing DAI ; Zu-Qi CHEN ; De-Liang QIU
The Chinese Journal of Clinical Pharmacology 2024;40(2):205-209
Objective To investigate the effect of vecuronium bromide on the malignant biological behavior of gastric cancer cells and its molecular mechanism.Methods Gastric cancer cells HGC-27 were divided into control group,experimental-L,-M,-H groups,si-NC group,si-FGD5-AS1 group,pcDNA-FGD5-AS1 group,pcDNA group,experimental-H+pcDNA group,experimental-H+pcDNA-FGD5-AS1 group.The control group was cultured conventionally;experimental-L,-M,-H groups were treated with 5,10 and 20μmol·mL-1 vecuronium bromide,respectively;si-FGD5-AS1 group and the si-NC group were transfected with lncRNA FGD5-AS1 interference expression vector and negative control plasmid,respectively;pcDNA-FGD5-AS1 group and pcDNA group were transfected with lncRNA FGD5-AS1 overexpression vector and negative control plasmid,respectively;lncRNA FGD5-AS1 overexpression vector and negative control plasmid were transfected into HGC-27 cells in the experimental-H+pcDNA-FGD5-AS1 group and experimental-H+pcDNA group,and then treated with 20 μmuol·mL-1 vecuronium bromide.Methyl thiazolyl tetrazolium(MTT),flow cytometry and real-time fluorescent quantitative polymerase chain reaction(RT-qPCR)were applied to dectect cell viability,apoptosis and lncRNA FGD5-AS1 expression.Results The cell activity of control group,experimental-L,-M,-H groups,si-NC group,si-FGD5-AS1 group,pcDNA group,PCDNA-FGD5-AS1 group,experimental-H+pcDNA group and experimental-H+PCDNA-FGD5-AS1 group were 1.31±0.07,0.58±0.03,1.31±0.06,0.51±0.03,1.29±0.08,1.68±0.15,0.59±0.03 and 1.16±0.06;the apoptosis rates were(6.49±0.44)%,(23.52±0.98)%,(6.42±0.44)%,(26.75±0.97)%,(6.72±0.38)%,(2.56±0.19)%,(23.56±1.04)%and(11.65±0.47)%;the expression levels of lncRNA FGD5-AS1 were 1.00±0.05,0.37±0.02,0.99±0.05,0.21±0.02,1.00±0.03,2.98±0.12,0.38±0.02 and 0.87±0.05,respectively.The above indexes were compared with the control group and experimental-H group,those in the si-FGD5-AS1 group were compared with the si-NC group,those in the pcDNA-FGD5-AS1 group were compared with the pcDNA group,and those in the experimental-H+pcDNA-FGD5-AS1 group were compared with the experimental-H+pcDNA group,the differences were statistically significant(all P<0.05).Conclusion Vecuronium bromide may inhibit the proliferation of HGC-27 cells and promote cell apoptosis by down-regulating lncRNA FGD5-AS1.
8.Clinical trial of brexpiprazole in the treatment of adults with acute schizophrenia
Shu-Zhe ZHOU ; Liang LI ; Dong YANG ; Jin-Guo ZHAI ; Tao JIANG ; Yu-Zhong SHI ; Bin WU ; Xiang-Ping WU ; Ke-Qing LI ; Tie-Bang LIU ; Jie LI ; Shi-You TANG ; Li-Li WANG ; Xue-Yi WANG ; Yun-Long TAN ; Qi LIU ; Uki MOTOMICHI ; Ming-Ji XIAN ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):654-658
Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50%(140 cases/184 cases)and 82.40%(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P>0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P>0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P>0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00%vs.64.50%,P>0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.
9.Grey-scale Reversed T1-weighted MRI for Detecting Structural Lesions of the Sacroiliac Joint in Patients with Axial Spondyloarthritis
Ximeng LI ; Wenjuan LI ; Ke ZHANG ; Chaoran LIU ; Yunfei ZHU ; Yingying ZHAN ; Mingzhu LIANG ; Guobin HONG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(3):412-419
[Objective]To analyze the value of grey-scale reversed T1-weighted(rT1)MRI in the detection of structur-al lesions of the sacroiliac joint(SIJ)in patients with axial spondyloarthritis(ax-SpA).[Methods]Fifty-two ax-SpA pa-tients who underwent both MRI and CT in our hospital within a week from February 2020 to December 2022 were retrospec-tively included.Both sacral and iliac side of each SIJ on oblique coronal images were divided into anterior,middle and pos-terior portion.Two radiologists reviewed independently three groups of MRI including T1-weighted imaging(T1WI),rT1 and T1WI+rT1 images to evaluate the structural lesions like erosions,sclerosis and joint space changes in each of the 6 re-gions of the SIJ.One of the radiologist did the evaluation again one month later.CT images were scored for lesions by a third radiologist and served as the reference standard.Intra-class correlation coefficients(ICC)were calculated to test the inter-and intra-reader agreement for the assessment of SIJ lesions.A Friedman test was performed to compare the lesion results of MRI and CT image findings.We examined the diagnostic performance[accuracy,sensitivity(SE)and specifici-ty]of different groups of MRI in the detection of lesions by using diagnostic test.A McNemar test was used to compare the differences of three groups of MRI findings.[Results]CT showed erosions in 71 joints,sclerosis in 65 and joint space changes in 53.Good inter-and intra-reader agreements were found in three groups of MRI images for the assessment of le-sions,with the best agreement in T1WI+rT1.There were no difference between T1WI+rT1 and CT for the assessment of all lesions,nor between rT1 and CT for the assessment of erosions and joint space changes(P>0.05).T1WI+rT1 yielded better accuracy and SE than T1WI in detection of all lesions(Accuracy erosions:90.3%vs 76.9%;SE erosions:91.6%vs 76.1%;Accu-racy sclerosis:89.4%vs 80.8%;SE sclerosis:84.6%vs 73.9%;Accuracy joint space changes:86.5%vs 73.1%;SE joint space changes:84.9%vs 60.4%;P<0.05).rT1 yielded better accuracy and SE than T1WI in detection of erosions and joint space changes(Accuracy erosions:87.5%vs 76.9%;SE erosions:88.7%vs 76.1%;Accuracy joint space changes:85.6%vs 73.1%;SE joint space changes:83.0%vs 60.4%;P<0.05).[Conclusions]In the detection of SIJ structural lesions in ax-SpA,rT1 improves the diagnostic perfor-mance and T1WI+rT1 is more superior to others.
10.Clinical implications of Naples prognostic scores in patients with resectable Siewert type II-III adenocarcinoma of the esophagogastric junction
Peng JIN ; Gang MA ; Yong LIU ; Bin KE ; Hongmin LIU ; Han LIANG ; Rupeng ZHANG
Chinese Journal of Gastrointestinal Surgery 2024;27(1):54-62
Objective:To evaluate the clinical value of preoperative Naples prognostic scores (NPS) in patients with resectable Siewert type II-III esophagogastric junction adenocarcinoma (AEG).Methods:In this retrospective observational study we collected and analyzed relevant data of patients with Siewert Type II-III AEG treated in the Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital from January 2014 to December 2018. NPS were calculated using preoperative albumin concentration, total cholesterol concentration, neutrophil/lymphocyte ratio, and lymphocyte/monocyte ratio and used to allocate patients into three groups: NTS-0 (0 points), NTS-1 (1-2 points) and NTS-2 (3-4 points). Kaplan–Meier was used to calculate disease-free survival (DFS) and overall survival (OS) in each NPS group and the log-rank test to compare these groups. Univariate and multivariate survival analyes were performed using the Cox regression model. Time-dependent receiver operating characteristic curves were constructed to compare the relationships between four commonly used tools for evaluating inflammatory responses and nutritional status:NPS, systemic inflammatory response scores, nutrient control status (CONUT), and prognostic nutrition index (PNI).Results:The study cohort comprised 221 patients with AEG of median age 63.0 (36.0–87.0) years. There were 190 men (86.0%) and 31 women (14.0%). As to pTNM stage, 47 patients (21.3%) had Stage I disease, 68 (30.8%) Stage II, and 106 (48.0%) Stage III. One hundred and forty-seven patients (66.5%) had Siewert Type II disease and 74 (33.5%) Siewert type III. There were 45 patients (20.4%) in the NPS-0, 142 (64.2%) in the NPS-1 and 34 (15.4%) in the NPS-2 groups. Higher NPS scores were significantly associated with older patients (χ2=5.056, P=0.027) and higher TNM stages ( H=5.204, P<0.001). The median follow-up was 39 (6-105) months; 16 patients (7.2%) were lost to follow-up. The median OS in the NPS-0, NPS-1, and NPS-2 groups were 78.4, 63.1, and 37.0 months, respectively; these differences are statistically significant ( P=0.021). Univariate and multivariate Cox regression analysis identified the following as independently and significantly associated with OS in patients with Siewert Type II-III: TNM stage (Stage II: HR=2.182, 95%CI: 1.227-3.878, P=0.008; Stage III: HR=3.534, 95%CI: 1.380-6.654, P<0.001), tumor differentiation (G3: HR=1.995, 95%CI: 1.141-3.488, P=0.015), vascular invasion (HR=2.172, 95%CI: 1.403-3.363, P<0.001), adjuvant chemotherapy (HR=0.326, 95%CI: 0.200-0.531, P<0.001), NPS (NPS-1: HR=2.331, 95%CI: 1.371-3.964, P=0.002; NPS-2: HR=2.494, 95%CI: 1.165-5.341, P=0.019), SIS group (NPS-1: HR=2.170, 95%CI: 1.244-3.784, P=0.006; NPS-2: HR=2.291, 95%CI: 1.052–4.986, P=0.037), and CONUT (HR=1.597, 95% CI: 1.187-2.149, P=0.038). The median DFS in the NPS-0, NPS-1, and NPS-2 groups was 68.6, 52.5, and 28.3 months, respectively; these differences are statistically significant ( P=0.009). Univariate and multivariate Cox regression analysis identified the following as independently and significantly associated with DFS in patients with Siewert Type II-III AEG: TNM stage (StageⅡ: HR=2.789, 95%CI:1.210-6.428, P=0.016; Stage III: HR=10.721, 95%CI:4.709-24.411, P<0.001), adjuvant chemotherapy (HR=0.640, 95% CI: 0.432-0.946, P=0.025), and NPS (NPS-1: HR=1.703, 95%CI: 1.043-2.782, P=0.033; NPS-2: HR=3.124, 95%CI:1.722-5.666, P<0.001). Time-dependent receiver operating characteristic curves showed that NPS was more accurate in predicting OS and DFS in patients with Siewert Type II-III AEG than were systemic inflammatory response scores, CONUT, or PNI scores. Conclusion:NPS is associated with age and TNM stage, is an independent prognostic factor in patients who have undergone resection of Siewert type II-III AEG, and is better than SIS, CONUT, or PNI in predicting survival.

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