ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, contact tracers were under immense pressure to deliver effective and timely contact tracing, raising concerns of higher susceptibility to burnout. Our study aimed to determine burnout prevalence among hospital-based contact tracers and associated risk factors, so that interventions to reduce burnout risk could be formulated. METHODS: One hundred and ninety-six active contact tracers across three hospitals within a healthcare cluster were invited to complete an anonymous online survey. To identify burntout, data such as demographics, work-related variables and contact tracing-related variables were collected using the Copenhagen Burnout Inventory. Associated factors were identified using multivariate statistics. Open-ended questions were included to understand the challenges and potential improvements through qualitative analysis. RESULTS: A total of 126 participants completed the survey, giving a completion rate of 64%, and almost half of these participants (42.9%) reported burnout. Protective factors included being on work-from-home arrangements (adjusted odds ratio [OR] 0.22, 95% confidence interval [CI] 0.08-0.56), perception of being well supported by their institution (adjusted OR 0.25, 95% CI 0.08-0.80) and being married (adjusted OR 0.28, 95% CI 0.12-0.64). Risk factors included having an administrative role pre-COVID-19 (adjusted OR 3.62, 95% CI 1.33-9.83). Work-related burnout was related to being activated for more than 1 day in the preceding week (unadjusted OR 3.25, 95% CI 1.33-7.94) and multiple activations in a day (unadjusted OR 3.54, 95% CI 1.44-4.41). Biggest challenges identified by participants were language barrier (62.7%), followed by workflow-related issues (42.1%). CONCLUSION Our study demonstrated burnout and other challenges faced by a team of mostly hospital-based administrative staff redeployed on a part-time basis to ensure timely contact tracing. To mitigate burnout, we recommend choosing staff on work-from-home arrangements and ensuring adequate manpower and rostering arrangements.
Humans ; COVID-19/epidemiology* ; Burnout, Professional/epidemiology* ; Singapore/epidemiology* ; Female ; Male ; Cross-Sectional Studies ; Adult ; Middle Aged ; Risk Factors ; Surveys and Questionnaires ; Contact Tracing/methods* ; SARS-CoV-2 ; Prevalence ; Pandemics

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals ; Disease Models, Animal ; Mice ; Pneumonia/genetics* ; Medicine, Chinese Traditional ; Male ; Humans ; Cytokines/immunology* ; Female ; Lipopolysaccharides/adverse effects* ; Lung/drug effects* ; Drugs, Chinese Herbal ; Ovalbumin ; Mice, Inbred BALB C

OBJECTIVE: To investigate the short-term clinical effect of closed reduction single arm external fixator combined with percutaneous needle fixation in the treatment of C1 distal radius fracture in elderly patients. METHODS: Between December 2022 and December 2023, a total of 60 elderly patients diagnosed with type C1 distal radius fractures were treated, comprising 9 males and 51 females. The age ranged from 65 to 84 years old, with an average of (72.69±8.14) years old. Among them, there were 18 cases on the left side and 42 cases on the right side. There were 55 cases of falling injury and 5 cases of traffic accident injury. According to the different surgical methods, the patients were divided into observation group and control group, with 30 cases in each group. The control group underwent manual reduction and unilateral external fixator fixation, consisting of 4 males and 26 females. The mean age was (72.54±8.67) years old. The body mass index (BMI) was (20.61±2.17) kg·m^-2. There were 10 cases on the left side and 20 cases on the right side. Among them, there were 27 cases of falling injury and 3 cases of traffic accident injury. The observation group was treated with manual reduction and unilateral external fixator combined with percutaneous Kirschner wire fixation, including 5 males and 25 females. The mean age was (72.76±7.23) years old. BMI (20.82±2.03) kg·m^-2. The left side was involved in 8 cases and the right side in 22 cases. There were 28 cases of falling injury and 2 cases of traffic accident injury. The changes in radial height, ulnar declination, palmar inclination angle parameters and patient-rated wrist evaluation (PRWE) were assessed on X-ray films before surgery, 2 days after surgery, and 12 weeks after surgery between the two groups. RESULTS: All surgical procedures were successfully completed in both groups without any significant complications. All patients were followed up for a duration from 12 to 20 weeks with an average of(14.50±2.78) weeks. The two groups exhibited significant differences in radial height, palmar inclination angle, and ulnar deviation angle at 2 days and 12 weeks post-operation (P<0.05). However, there was no statistically significant difference observed in radial height, palmar inclination, and ulnar deviation between the two groups at 2 days after the operation (P>0.05). There were significant differences in radial height, palmar inclination angle, and ulnar deviation between the two groups at 12 weeks after operation (P<0.05). At 2 days and 12 weeks after the operation, there were significant differences in PRWE scores of the two groups compared with preoperative scores(P<0.05). At 2 days after the operation, there was no significant difference in PRWE score between the two groups (P>0.05). The PRWE score showed a significant difference between the two groups at 12 weeks post-operation(P<0.05). CONCLUSION The combination of closed reduction and unilateral external fixator, along with percutaneous pin fixation provides move stable fixation for type C1 distal radius fractures. Gradual removal of external fixator further facilitatse the recovery of wrist joint function.
Humans ; Male ; Female ; Radius Fractures/surgery* ; External Fixators ; Aged ; Aged, 80 and over ; Bone Wires ; Fracture Fixation/instrumentation* ; Wrist Fractures

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

Objective:To investigate the clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumor (GIST) with initial surgical resection.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 847 GIST patients who under-went initial surgical resection in Tianjin Medical University Cancer Institute & Hospital from January 2011 to December 2020 were collected. There were 405 males and 442 females, aged (60±10)years. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the nonparameter rank sum test. The Kaplan-Meier method was used to calculate survival rates. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX regression model. Results:(1) Clinicopatholo-gical characteristics. Of 847 patients, the tumor primary location was stomach in 585 cases, jejunum and ileum in 142 cases, duodenum in 76 cases, colorectum in 10 cases, esophagus in 3 cases, and extra-gastrointestinal in 31 cases. There were 13 cases with liver metastasis and 22 cases with abdominal metastasis. The tumor maximum diameter was (7±5)cm, and the number of nuclear divisions was 4(range, 0-60) cells/50 high-power field or 5 mm 2. According to risk classification of National Institutes of Health (NIH), 31 cases were of extremely low risk, 238 cases were of low risk, 213 cases were of moderate risk, 365 cases were of high risk. There were 839 of 847 patients positive for CD117, 788 cases positive for Dog-1, 710 cases positive for CD34, respectively. There were 272 cases with Ki-67 <5%, 214 cases with Ki-67 of 5%- 9%, 198 cases with Ki-67 ≥10%, 163 cases with missing data. R 0 resection was in 814 cases and non-R 0 resection was in 33 cases. (2) Gene testing and postoperative adjuvant therapy of GIST patients. ① Gene testing. Of 847 patients, 424 underwent genetic testing. The proportion of genetic testing was 1.89%(1/53) in 2011, 9.76%(8/82) in 2012, 8.45%(6/71) in 2013, 15.66%(13/83) in 2014, 50.00%(40/80) in 2015, 55.26%(42/76) in 2016, 73.86%(65/88) in 2017, 68.27%(71/104) in 2018, 80.65%(75/93) in 2019, 88.03%(103/117) in 2020, respectively. Of 424 with genetic testing, 338 cases had KIT mutation, 31 cases had PDGFRA mutation, 55 cases were wild type. ② Adjuvant therapy. Of 847 patients, 253 patients underwent postoperative adjuvant therapy. The proportions of postoperative adjuvant therapy were 8.82%(21/238), 41.78%(89/213), 39.18%(143/365) in patients of low risk, moderate risk, high risk. Of 578 patients with moderate to high risk, the proportion of postoperative adjuvant therapy was 15.15%(5/33) in 2011, 14.71%(10/68)in 2012, 22.45%(11/49) in 2013, 29.09%(16/55) in 2014, 41.38%(24/58) in 2015, 46.15%(24/52) in 2016, 32.81%(21/64)in 2017, 60.00%(45/75) in 2018, 60.42%(29/48) in 2019, 61.84%(47/76) in 2020, respectively. Of 253 patients underwent postoperative adjuvant therapy, 247 cases received imatinib had 6 cases received sunitinib. (3) Comparison of clinicopathological characteristics of GIST with non-gastric origin and gastric origin. Of 847 patients, 262 cases had non-gastric origin and 585 cases had gastric origin. There were significant differences in gender, the number of tumor, tumor maximum diameter, Ki-67 index, risk classification of NIH, and R 0 resection between the two groups ( χ2=8.62, 8.40, 12.97, 6.57, Z=-6.15, χ2=17.19, P<0.05). (4) Analysis of influencing factors for recurrence-free survival rate in GIST patients. Results of multivariate analysis showed that the year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classification of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy were independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection ( hazard ratio=0.58, 0.61, 2.00, 1.71, 5.81, 2.56, 0.65, 0.38, 95% confidence interval as 0.39-0.85, 0.45-0.83, 1.46-2.74, 1.24-2.35, 3.16-10.69, 1.63-4.02, 0.46-0.94, 0.25-0.56, P<0.05). Conclusions:GIST with initial surgical resection is common located in stomach, with high positive rate in CD117 and Dog-1. The number of people undergoing genetic testing and targeted therapy for GIST is increasing year by year. There are significant differ-ences in clinicopathological characteristics between GIST with non-gastric origin and gastric origin. The year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classifica-tion of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy are independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection.

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.

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.