Objective To establish an individualized nomogram model and evaluate its efficacy to provide a possible evaluation basis for the prognosis of lower third and abdominal part of oesophageal adenocarcinoma (EAC). Methods Lower third and abdominal part of EAC patients from 2010 to 2015 were chosen from the SEER Research Plus Database (17 Regs, 2022nov sub). The patients were randomly allocated to the training cohort and the internal validation cohort with a ratio of 7∶3 using bootstrap resampling. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) in EAC patients, which would be elected to construct the nomogram prediction model. C-index, calibration curve and receiver operating characteristic (ROC) curve were performed to evaluate its efficacy. Finally, the efficacy to evaluate the OS of EAC patients was compared between the nomogram prediction model and TNM staging system. Results In total, 3945 patients with lower third and abdominal part of EAC were enrolled, including 3475 males and 470 females with a median age of 65 (57-72) years. The 2761 patients were allocated to the training cohort and the remaining 1184 patients to the internal validation cohort. In the training and the internal validation cohorts, the C-index of the nomogram model was 0.705 and 0.713, respectively. Meanwhile, the calibration curve also suggested that the nomogram model had a strong capability of predicting 1-, 3-, and 5-year OS rates of EAC patients. The nomogram also had a higher efficacy than the TNM staging system in predicting 1-, 3-, and 5-year OS rates of EAC patients. Conclusion This nomogram prediction model has a high efficiency for predicting OS in the patients with lower third and abdominal part of EAC, which is higher than that of the current TNM staging system.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Objective: To explore the association between negative life events and smartphone addiction among middle school students, so as to provide theoretical support and practical guidance for prevention and intervention of smartphone addiction among middle school students. Methods: Using cluster sampling, 8 890 students were selected to survey from 27 junior high schools and 3 senior high schools in a district of Shenzhen in 2022 (baseline) and 2023 (followup). Data were collected through selfresigned questionnaires on basic information, the Smartphone Addiction Scale-Short Version, and the Adolescent Selfrating Life Events Checklist. Mixedeffects models were employed to analyze the association. Results: Compared to 2022, the punishment scores of middle school students in 2023 [1.00 (0.00, 6.00) and 1.00 (0.00, 6.00)] decreased (Z=4.27), while the scores of interpersonal stress, learning stress and adaptation [4.00(0.00, 8.00), 4.00(0.00, 8.00); 4.00(1.00, 8.00), 5.00(2.00, 9.00); 2.00 (0.00, 6.00), 3.00 (0.00, 7.00)] increased (Z=-3.04, -8.36, -6.80) (P<0.01). Mixedeffects models revealed a positive doseresponse relationship between negative life events and smartphone addiction (OR=1.08-1.17, P<0.01). Stepwise regression showed independent positive effects of interpersonal stress (OR=1.05), academic stress (OR=1.03), and adaptation stress (OR=1.11) on smartphone addiction (P<0.01). Subgroup analysis of nonaddicted students in 2022 confirmed persistent associations for academic stress (OR=1.03) and adaptation (OR=1.07) (P<0.01). Conclusion Negative life events exhibit a positive doseresponse relationship with smartphone addiction, particularly interpersonal stress, academic stress, and adaptationrelated events.

Objective: To explore the potential causal association between adolescent compulsive behaviour and smartphone addiction based on longitudinal data, so as to provide reference for the establishment of adolescent smartphone addiction interventions. Methods: A preliminary survey and follow-up were conducted on 8 907 middle and high school students in a district of Shenzhen in 2022 and 2023, respectively. Compulsive behaviours were measured by using the Mental Health Inventory for Middle School Students-60 Items (MMHI-60), smartphone addiction was assessed by using the Smartphone Addiction Scale-Short Version ( SAS- SV), and the associations between compulsive behaviours and smartphone addiction were analysed by using multilevel mixed-effects models and subgroup analyses. Results: Smartphone addiction detection rates among middle school students were significantly associated with genders, father s education level, mother s education level, study load subgroups, and whether or not they were single-parent families, and there were statistical differences ( χ 2=17.21-175.34, P <0.05). Students with compulsive behaviours were 2.98 times more likely to develop smartphone addiction than those without compulsive behaviours ( OR=2.98, 95%CI=2.77-3.22, P <0.05). Subgroup analysis of middle school students without smartphone addiction in the first year found that compulsive behaviours significantly predicted smartphone addiction ( OR= 1.76 , 95%CI=1.54-2.01, P <0.05). Conclusion There is a potential causal association between obsessive-compulsive behaviours and smartphone addiction in middle school students, and obsessive-compulsive behaviours in middle school students could significantly predicted the occurrence of smartphone addiction.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

OBJECTIVE: Benzylisoquinoline alkaloids (BIAs) have pharmacological functions and clinical use. BIAs are mainly distributed in plant species across the order Ranunculales and the genus Phellodendron from Sapindales. The BIA biosynthesis has been intensively investigated in Ranunculales species. However, the accumulation mechanism of BIAs in Phellodendron is largely unknown. The aim of this study is to unravel the biosynthetic pathways of BIAs in Phellodendron amurens. METHODS: The transcriptome and metabolome data from 18 different tissues of P. amurense were meticulously sequenced and subsequently subjected to a thorough analysis. Weighted gene co-expression network analysis (WGCNA), a powerful systems biology approach that facilitates the construction and subsequent analysis of co-expression networks, was utilized to identify candidate genes involved in BIAs biosynthesis. Following this, recombinant plasmids containing candidate genes were expressed in Escherichia coli, a widely used prokaryotic expression system. The purpose of this genetic engineering endeavor was to express the candidate genes within the bacteria, thereby enabling the assessment of the resultant enzyme activity. RESULTS: The synonymous substitutions per synonymous site for paralogs indicated that at least one whole genome duplication event has occurred. The potential BIA biosynthetic pathway of P. amurense was proposed, and two PR10/Bet v1 members, 14 CYP450s, and 33 methyltransferases were selected as related to BIA biosynthesis. One PR10/Bet v1 was identified as norcoclaurine synthase, which could catalyze dopamine and 4-hydroxyphenylacetaldehyde into (S)-norcoclaurine. CONCLUSION Our studies provide important insights into the biosynthesis and evolution of BIAs in non-Ranunculales species.

Objective To evaluate the efficacy of XELOX regimen as neoadjuvant chemotherapy in the treatment of stage Ⅱ and Ⅲ colon cancer.Methods The clinical data of 50 patients with clinical stage Ⅱ(T4)Ⅲ colon cancer who underwent laparoscopic radical resection at general surgery department of our hospital from January 1,2012 to January 1,2021 were retrospectively analyzed.Patients were divided into neoadjuvant chemotherapy group(NACT)and adjuvant chemotherapy group(ACT)according to whether they received neoadjuvant chemotherapy with XELOX regimen.The general clinical data,adverse reactions of chemotherapy,surgical complications,operation time,intraoperative blood loss,hospitalization time,hospitalization cost,negative conversion rate of tumor markers,tumor remission rate,tumor downstaging rate,tumor response grade after chemotherapy,postoperative disease-free survival curve,and overall survival curve were retrospectively analyzed and compared among the groups.Results There were no significant differences in operative complications,postoperative exhaust time and hospital stay between NACT group and ACT group(P＞0.05).The adverse reactions of chemotherapy,the negative conversion rate of postoperative CEA and CA19-9,the duration of operation,the amount of bleeding,and the hospitalization cost in NACT group were significantly better than those in ACT group(P＜0.05).In terms of DFS and OS survival curves,with the extension of time,the decline of the NACT survival curve was smaller than that of the ACT group,and there was a significant difference in DFS survival curve(P＜0.05),but no significant difference in OS survival curve(P＞0.05).Conclusion XELOX neoadjuvant chemotherapy is safe and effective in the treatment of stage Ⅱ(T4)and stage Ⅲcolon cancer.

Objective To analyze blood lipid levels in patients with myelodysplastic syndrome(MDS)and further explore the factors associated with abnormal blood lipids.Methods Eighty-eight newly diagnosed MDS patients were selected as the study group,and 100 healthy subjects were selected as the control group.Fasting blood lipid levels,triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),apolipoprotein A1(ApoA1)and ApoB were detected before treatment in the study group and the control group.The differences of serum lipid levels in MDS patients with different WHO-MDS classification,modified International Prognostic Score System(IPSS-R)karyotype,risk stratification and TP53 mutation were investigated.The correlation between ApoA1 level and clinical indicators of MDS patients was analyzed,and clinical indicators of different ApoA1 level groups were compared.Results The levels of TC,HDL-C,LDL-C,ApoA1 and ApoB were significantly lower in the study group than those in the control group(P＜0.01).There were no significant differences in TG,TC,HDL-C,LDL-C,ApoA1 and ApoB levels between different subgroups.The ApoA1 level was lower in the IPSS-R high-risk stratification group than that of the IPSS-R low-risk stratification group(P＜0.05).There were no significant differences in lipid levels between the different karyotype groups.The level of ApoA1 was lower in the TP53 mutant group than that in the non-TP53 mutant group(P＜0.05).Correlation analysis showed that ApoA1 level was positively correlated with body mass index(BMI,P＜0.05),and negatively correlated with patient age,percentage of bone marrow original cells,IPSS-R karyotype grouping,IPSS-R risk grouping and TP53 gene mutation(P＜0.05).The BMI level was lower in the low ApoA1 group than that of the high ApoA1 group(P＜0.05).The percentage of bone marrow original cells and TP53 gene mutation rate of MDS patients were higher in the low ApoA1 group than those in the high ApoA1 group(P＜0.05).Conclusion The plasma lipid level in MDS patients is significantly lower than that of healthy controls,and levels of ApoA1 varied significantly in different disease states,which may be associated with TP53 gene mutation.

Objective:To explore characteristics of intestinal flora in patients with rheumatoid arthritis complicated with inter-stitial lung disease(RA-ILD),to analyze its influencing factors,and to explore improvement of intestinal flora in patients with RA-ILD by different treatment methods.Methods:A total of 100 patients with RA-ILD who visited Shijiazhuang People's Hospital from June 2021 to June 2022 were selected as research objects,and 100 healthy patients in Shijiazhuang People's Hospital during same pe-riod were selected as healthy group.High throughput sequencing was performed on intestinal flora of two groups,OTU flora abundance and α-Diversity,β-diversity,flora distribution and LEfSe difference were analyzed.Another 100 patients with RA-ILD were randomly divided into group A(n=50)and group B(n=50).Group A was treated with leflunomide+nidanib or pifenidone,and group B was treated with leflunomide+nidanib or pifenidone+bifidobacterium triad.Improvement of intestinal flora in two groups after treatment was analyzed.Correlation analysis was used to determine correlation between changes of intestinal flora and clinical characteristics and indicators in RA-ILD patients.Results:OTU flora abundance,α-diversity and β-diversity in RA-ILD patients were lower than that of healthy people.Abundance of Intestinibacter in RA-ILD group was higher than that in healthy group,and abundance of Lactobacillus,Escherichia coli,Klebsiella,Candidatus saccharimonas,Odoribacter and Enterococcus in RA-ILD group were lower than that in healthy group.After treatment,flora structure of group A and group B was improved.Group B was closer to healthy population,and cu-rative effect was significantly better than that of group A.Integinibacter bacteria level was positively correlated with age,RA course,DAS28,CRP,RF and KL-6(P<0.05),and negatively correlated with DLCO(P<0.05).Lactobacillus level was negatively correlated with course of RA,DAS28,CRP,RF,IL-6(P<0.05),and positively correlated with VC(P<0.05);Shigella coli level was negtively correlatied with RA course,ILD course,DAS28,ESR,RF,TNF-α(P<0.05).Klebsiella level was positively correlated with VC and DLCO(P<0.05);Bacterial level of Candida saccharimonas was negatively correlated with DAS28,ESR,CRP,RF,IL-6,TNF-α(P<0.05)and positive correlated with DLCO(P<0.05);Odoribacter bacteria level was negatively correlated with DAS28,CRP,RF,IL-6 and KL-6(P<0.05),and positively correlated with VC(P<0.05);Enterococcus level was negatively correlated with course of RA,ILD,DAS28,ESR,RF and KL-6(P<0.05),while positively correlated with DLCO(P<0.05).Conclusion:Intestinal microflora abundance of RA-ILD patients is significantly lower than that of healthy people,and there aree significant differences in some microflora,which are closely related to clinical characteristics and indicators.Using of bifidobacterium triad in clinical treatment is helpful to improve intestinal flora of RA-ILD patients.