Objective The study aimed to construct and validate a predictive model for pulmonary nodules(PN)nature based on clinicopa-thological features,imaging,and serum biomarkers,so as to provide scientificdecision-making for early diagnosis and treatment of lung cancer.Methods A retrospective was performed on 816 PN patients with definited pathological diagnosis who received surgical resection analysisor lung biopsy in the Department of Thoracic Surgery and Oncology of Shenzhen Traditional Chinese Medicine Hospital from January 2019 to February 2023.Among them,113 cases that did not meet the inclusion criteria were excluded,and the remaining 703 cases were included in the study.The study based on the clinicopathologic features(age,gender,smoking history,smoking cessation history and family history of cancer),chest imaging(maximum diameter of nodule,location of lesion,clear border,Lobulation,spiculation,vascular convergence sign,vacuole,calcification,air bronchial sign,emphysema,nodule type and pleural indentation,nodule number)and serum carcinoembryonic antigen(CEA),cytokeratin 19 fragment(CYFRA21-1),squamous cell carcinoma antigen(SCCA)in patients with PN.These cases were randomly divided into a modeling group(n=552,237 benign,315 malignant)and a validation group(n=151,85 benign,66 malignant).First,univariate analysis was performed to screen for statistically significant predictors of nodules nature.Then,multivariate regression analysis was performed to screen for independent predictors of nodules nature.Finally,the prediction model of PN nature was constructed by logistic regression analysis.Subsequently,the validation group data were entered into the proposed model and Mayo clinic(Mayo)model,veterans affairs(VA)model,Brock University(Brock)model,Peking University(PKU)model and Guangzhou Medical University(GZMU)model,respectively.PN malignancy probability was calculated.The receiver operating characteristic(ROC)curves were plotted.The diagnostic efficiency of each model was compared according to the area under the curve(AUC).Results There were statistically significant variables including age,family history of cancer,maximum nodule diameter,nodule type,upper lobe of lung,calcification,vascular convergence sign,lobulation,clear border,spiculation,and serum CEA,SCCA,CYFRA21-1 using univariate analysis.Multiple regression analysis showed that age,CEA,clear border,CYFRA21-1,SCCA,upper lobe of lung,maximum nodule diameter,family history of cancer,spiculation and nodule type were independent predictors of PN nature.The prediction model equation constructed in this study is as follows:f(x)= ex/(1+ex),X=(-6.318 8+0.020 8×Age+0.527 4×CEA-0.928 4×clear border+0.294 6×Cyfra21-1+0.294×maximum nodule diameter+1.220 1×family history of cancer +0.573 2×upper lobe of lung +0.064 8×SCCA +1.461 5×Spiculation +1.497 6×nodule type).The AUC(0.799 vs 0.659,0.650)of the proposed model was significantly higher compared with Mayo model and VA model,and there were statistically significant differences(Z=3.029,2.638,P=0.003,0.008).However,compared with Brock model,PKU model and GZMU model,the differences of AUC(0.799 vs 0.762,0.773,0.769)were not statistically significant(Z=1.063,0.686,0.757,P=0.288,0.493,0.449).Conclusion The prediction model for PN nature established in this study is accurate and reliable,which can help clinics with early diagnosis and early intervention,and this prediction model deserves to be popularized.

BACKGROUND:Grape seed extract has been shown to be effective in inhibiting the growth of androgen-dependent tumors(e.g.,breast cancer),and thus grape seed extract could theoretically inhibit epiphyseal closure induced by estrogen in late adolescence. OBJECTIVE:To screen the effects of grape seed extract on apoptosis of growth plate chondrocytes and epiphyseal closure in rats. METHODS:(1)In vitro experiment:Growth plate chondrocytes from rat large tibia and femur at logarithmic growth stage were obtained and cultured in groups:normal control group,model control group(adding 17β-estradiol to induce apoptosis),positive control group(adding letrozole and 17β-estradiol),grape seed extract group(adding 17β-estradiol and 10 μg/mL grape seed extract),Caspase-9 inhibitor group(adding 17β-estradiol and Caspase-9 inhibitor),Caspase-9 agonist group(adding 17β-estradiol and Caspase-9 agonist).Cell apoptosis was detected by flow cytometry after 48 hours of culture.(2)In vivo experiment:Thirty 3-month-old Sprague-Dawley rats were randomly divided into model control group,positive control group and low-,medium-and high-dose groups,with five rats in each group.All rats were injected subcutaneously with 17β-estradiol(3 times per week)to establish epiphyseal closure models,followed by intragastric administration of letrozole in positive control group and 0.05,0.2 and 0.8 g/kg grape seed extract in low-,medium-and high-dose groups,respectively,once a day until over 2/3 of the epiphyseal plate in the model control group was closed.The length of the tibia was then observed.Another 18 Sprague-Dawley rats were randomly divided into model control group,positive control group,and medium-dose group,with 6 rats in each group,treated as above for 1.5 continuous months.The expression of Caspase-9 protein in rat growth plate cartilage was detected by western blot. RESULTS AND CONCLUSION:(1)In vitro experiment:17β-estradiol could induce apoptosis in growth plate chondrocytes,and letrozole,grape seed extract,and caspase-9 inhibitors could all inhibit apoptosis in growth plate chondrocytes.(2)In vivo experiment:When more than 2/3 of the epiphyseal plate in the model control group was closed,the number of rats with epiphysis closure in the positive control and medium-dose groups was less than that in the model control group(P＜0.05),and the tibial length was longer than that in the model control group(P＜0.05),and the Caspase-9 protein expression in the tibial growth plate was lower than that in the model control group(P＜0.05).To conclude,the appropriate dose of grape seed extract can effectively inhibit the apoptosis of growth plate chondrocytes and delay epiphyseal closure,which has the potential to promote bone growth.

Objective To investigate the expression and clinical significance of CD155 in oral squamous cell carci-noma(OSCC)tissues,as well as its impact on migration,proliferation and invasion.Methods Immunohisto-chemistry(IHC)was used to analyze the expression of CD155 in OSCC tissues and its correlation with clinicopath-ological features and prognosis.The transcription levels of CD155 were assessed by Western blot and RT-qPCR.Cell experiments were conducted to evaluate the effects of CD155 on OSCC cells following transfection with CD155 siRNA.Results CD155 was predominantly expressed on the cell membrane in OSCC tissues,with higher expres-sion levels compared to normal tissues(x2=50.750,P＜0.000 1).High CD155 expression was associated withⅢ+Ⅳ disease stages(x2=25.488,P=0.001),poor differentiation(x2=6.299,P=0.012),T3+T4 depth of invasion(x2=23.820,P=0.001)and lymph node metastasis(x2=7.830,P=0.005)in OSCC patients;survival analysis revealed a correlation between high CD155 expression and shorter patient survival(P＜0.05).COX regression analysis identified lymph node metastasis as an independent factor affecting the survival of OSCC patients(P＜0.05).Both CD155 protein expression and mRNA transcription levels were significantly upregulated in OSCC cells(P＜0.05).Transfection with siRNA-CD155 in OSCC cells resulted in significantly reduced prolif-eration,migration and invasion abilities compared to the control group(P＜0.05).Conclusion CD 155 is highly expressed in OSCC tissues and is associated with poor patient prognosis.Modulating CD155 expression can influ-ence the biological functions of OSCC cells,leading to and inhibition of proliferation,migration,and invasion.

Objective:To study the antitumor activity of zeylenone in colorectal cancer and its related regulatory mechanism.Methods:Human colorectal cancer cells(DLD-1 and HCT116)and control cell(HcoEpic)were treated with different concentrations of zeylenone(0,2.5,5,10 and 20 μmol/L)for 48 h.Cell viability of DLD-1,HCT116 and HcoEpic were determined by CCK-8 kit.TUNEL staining was used to evaluate cell apoptosis.Caspase-3 activity and LDH level were measured by ELISA.Relative levels of M1 and M2 polarization markers,p-PI3K/PI3K and p-AKT/AKT were detected by Western blot and qRT-PCR.DLD-1 cells were subcuta-neously injected into the armpit of nude mice to establish a mouse xenograft tumor model.Intraperitoneal dose of zeylenone given to nude mice was 30 mg/kg,administered once every two days.After 2 weeks,the effect of zeylenone on growth of colorectal cancer tumors was detected.Results:Zeylenone inhibited cell activity and promoted cell apoptosis in colorectal cancer cells.Additionally,zeylenone stimulated M1-polarization and inhibited M2-polarization of tumor-associated macrophages(P<0.05).PI3K/AKT signaling pathway was inhibited by zeylenone in colorectal cancer cells(P<0.05).PI3K/AKT signaling pathway activator(740 Y-P)attenuated the effect of zeylenone on colorectal cancer cells.In mouse xenograft model,zeylenone inhibited the growth of colorectal cancer tumors(P<0.05).Conclusion:Zeylenone can inhibit colorectal cancer cell activity,promote colorectal cancer cell apoptosis,and promote M1 po-larization of tumor-associated macrophages by regulating PI3K/AKT signaling pathway,ultimately inhibiting the progression of colorec-tal cancer.

Objective To investigate the effects of endostatin combined with icotinib on chemotherapy sensitivity,tumor markers,and prognosis in patients with advanced non-small cell lung cancer(NSCLC).Methods A total of 88 patients with advanced NSCLC admitted to our hospital from January 2019 to August 2020 were selected and randomly assigned to two groups,with 44 patients in each group.The patients in both groups were treated with pemetrexed+cisplatin(PP)chemotherapy,whereas those in the control group were administered echitinib and those in the observation group was treated with endostatin combined with icotinib.Patients in the two groups were assessed for clinical efficacy,tumor markers[carbohydrate antigen(CA)50,carcinoembryonic antigen(CEA),cytokeratin 19 fragment(CYFRA)21-1],T lymphocyte subsets,microRNA expression levels(miR-34b,miR-204-5p,and miR-158-5p)and tyrosine protein excitation.We also examined janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathways,along with adverse reactions.Results We detected no significant differences between the two groups with respect the total response rate(P>0.05).Following treatment,the levels of serum CA50,CEA,and CYFRA21-1 in the observation group patients were found to be lower than those of patients in the control group(P<0.05).Similarly,the levels of CD3+,CD4+,CD4+/CD8+in observation group patients were higher than those in the control group patients,whereas the levels of CD8+were lower than those in the control patients(P<0.05).Furthermore,the expression levels of miR-34b,miR-204-5p,and miR-158-5p in the observation group patients were higher than those in the control group patients,whereas contrastingly,the levels of J AK2 and STAT3 mRNA expression were lower than those in the control group(P<0.05).In addition,the progression-free survival of the observation group patients was higher than that of control group patients(P<0.05).Conclusion The combination of endostatin and icotinib has clear therapeutic efficacy in patients with advanced NSCLC,which can con-tribute to enhancing their sensitivity to chemotherapy and immune function.We speculate that the underlying mechanisms of action may be associated with a reduction in the activity of the JAK2/STAT3 signaling pathway,which is beneficial for patient prognosis.

Toxoplasma gondii is an obligate intracellular parasite and causes serious harm to human and ani-mal health.In recent years,a large amount of research has been conducted on the immunological mechanism of toxo-plasmosis,especially in the immune privileged regions of the host,such as brain,eyes,and placenta.This review summaries the immunological mechanism required for resistance to toxoplasmosis,which may provide a valuable ref-erence for the diagnosis,treatment,and prevention studies.

Objective:To retrieve, evaluate and integrate the best evidence for cognitive behavioral therapy for improving psychosomatic symptoms in chronic obstructive pulmonary disease (COPD) patients.Methods:According to the "6S" model, evidence related to the cognitive behavioral therapy of COPD patients, including clinical practice guidelines, evidence summaries, expert consensus, systematic reviews and original research, was searched in UpToDate, Joanna Briggs Institute Center for Evidence-Based Health Care database, BMJ Best Practice, Cochrane Library, Guidelines International Network, National Institute for Health and Clinical Excellence, Registered Nurses' Association of Ontario, Medlive, Global Initiative for Chronic Obstructive Lung Disease, PubMed, Embase, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang database and VIP. The search deadline was from the establishment of the databases to November 21, 2022. Two researchers independently evaluated the quality of the literature and extracted and summarized evidence from the literature that met the quality standards.Results:A total of 13 articles were included, including 2 clinical decision-making articles, 3 guidelines, 1 expert consensus, 3 systematic evaluations, 1 Meta-analysis and 3 randomized controlled trials. Finally, 21 pieces of evidence were formed from three aspects, such as establishing trust relationships, cognitive therapy and behavioral therapy.Conclusions:This study summarizes the best evidence for cognitive behavioral therapy to improve psychosomatic symptoms of COPD patients, in order to provide evidence-based evidence for cognitive behavioral therapy in COPD patients.

Objective:To investigate the relationship between NUDT15 gene polymorphism and tolerance to treatment with 6-mercaptopurine (6-MP) in children with acute lymphoblastic leukemia (ALL).Methods:Fifty-eight children diagnosed with ALL in Shanxi Children's Hospital from January 2019 to December 2020 were recruited. All of them were treated with CCLG-ALL2018 chemotherapy regimen and the bone marrow showed complete remission. They received 6-MP oral treatment during maintenance treatment. Single nucleotide polymorphism of NUDT15 gene was detected by real-time fluorescence quantitative polymerase chain reaction. The bone marrow suppression after 6-MP treatment and 6-MP tolerance dose in patients with different NUDT15 genotypes were analyzed.Results:Among 58 patients, 3 patients had NUDT15 TT genotype, 46 patients had CC genotype and 9 patients had TC genotype. During maintenance treatment with 6-MP, the differences in leukocyte count, hemoglobin and platelet count among the three groups of patients with different NUDT15 genotypes were statistically significant (all P < 0.05). Among 58 patients, 23 (39.66%) patients had varying degrees of neutropenia after medication, including 16 cases of NUDT15 CC genotype, 5 cases of TC genotype and 2 cases of TT genotype. There was a statistically significant difference in bone marrow suppression among the three groups ( H = 29.10, P < 0.05). The dosages of 6-MP used in patients with TT, CC and TC genotypes were (10.4±8.8) mg·m -2·d -1, (41.5±1.3) mg·m -2·d -1 and (36.7±2.4) mg·m -2·d -1, respectively, and the difference was statistically significant ( F = 16.95, P < 0.05). Conclusions:Children with different NUDT15 genotypes have different tolerance to 6-MP, and NUDT15 gene polymorphism is associated with 6-MP intolerance during maintenance treatment in children with ALL, which may affect the treatment of the disease.

Objective:To evaluate the short-term efficacy and the improvement of quality of life of enzyme replacement therapy (ERT) with Imiglucerase on children with Gaucher disease(GD) through the same time monitoring.Methods:Six children diagnosed as GD who were treated by ERT with Imiglucerase in the Department of Hematology of the Children′s Hospital of Shanxi Province from May 2019 to May 2020 were recruited.Every 3 months, the sizes of the liver and spleen was palpated, the change of bone pain was recorded, and the haematological index was examed.The volumes of the liver and spleen at 1-year treatment were measured by CT.Bone involvement was examined by magnetic resonance imaging (MRI). In addition, the body weight, height, and the 36-Item Short Form Survey (SF-36) were measured and compared with pre-treatment levels.These data were analyzed statistically by SPSS 25.0 and the difference between pretherapy and post-treatment was compared by paired t test. Results:Six children diagnosed as GD received ERT with Imiglucerase.No adverse events were reported.Decreased volumes of the liver and spleen, and increased hemoglobin level and platelet count were detected after 3-6 months of ERT.After 1 year of ERT, hemoglobin level significantly increased compared with pre-treatment level ( t=4.200, P=0.008). Although the platelet count increased at 1-year ERT, it was comparable with pre-treatment level ( t=2.260, P=0.073). The volumes of liver and spleen decreased by (22.10±15.28)% ( t=2.725, P=0.042) and (47.10±18.42)% ( t=3.162, P=0.034) after 1 year of ERT, respectively.During the first year of ERT, the height and weight increased (6.17±2.86) cm ( t=5.286, P=0.003) and (4.08±2.01) kg ( t=4.975, P=0.004), respectively.SF-36 score increased significantly from (489.35±103.99) points to (632.75±73.34) points ( t=5.740, P=0.002). After 1 year of ERT, 1 patient still had bone pain, and 2 cases were worse in bone MRI, which may be attributed to the short period of follow-up and insufficient dose, and another 3 had no change in bone MRI. Conclusions:ERT ameliorates GD-associated anemia, organomegaly and growth retardation, and improves the growth rate of body mass and height and the quality of life in the short period.However, short-term ERT does not improve the bone disease.

Objective:To explore the clinical characteristics and prognostic factors of children with relapsed acute lymphoblastic leukemia (ALL).Methods:The clinical data of 52 children with relapsed ALL in Children's Hospital of Shanxi Province from January 2010 to April 2019 were retrospectively analyzed. The clinical characteristics of the children were summarized and the prognostic factors after recurrence were analyzed.Results:Till May 1, 2019, 5 out of 52 children gave up treatment after diagnosis and were lost to follow-up. For the remaining 47 children with successful follow-up, the median age at initial diagnosis was 60 months (11-168 months), the median time from initial diagnosis to relapse was 21 months (2-112 months), the median follow-up time was 5.5 months (1.0-69.0 months), and the 2-year overall survival (OS) rate after relapse was 31%. Nine patients accepted allogeneic hematopoietic stem cell transplantation after the second time complete remission, the median time from diagnosis to transplantation was 4.5 months (3.0-7.0 months), and the median follow-up time was 22 months (4-69 months). The 2-year OS rates in relapsed children with white blood cell count < 50×10 9/L and ≥ 50×10 9/L at initial diagnosis were 39% and 13%, respectively (χ 2=5.623, P=0.018). The 2-year OS rate after relapse in standard-risk, intermediate-risk and high-risk groups were 72%, 31% and 8%, respectively (χ 2=10.068, P=0.007). The 2-year OS rate after relapse in very early relapse, early relapse and late relapse groups were 0, 33% and 79%, respectively (χ 2=30.066, P < 0.01). The 2-year OS rate after relapse in chemotherapy with or without radiotherapy group, transplantation group and irregular treatment group were 57%, 89% and 0, respectively (χ 2=26.885, P < 0.01). Cox multivariate analysis showed that relapse time was the independent risk factor affecting the prognosis of children with relapsed ALL ( HR=0.340, 95% CI 0.146-0.789, P=0.012). Compared with the transplantation group, the risk of death in the chemotherapy with or without radiotherapy group and the irregular treatment group was significantly higher ( HR=12.313, 95% CI 1.266-119.758, P=0.031; HR=20.699, 95% CI 2.230-192.129, P=0.008), suggesting that hematopoietic stem cell transplantation is a protective factor for the prognosis of children with relapsed ALL. Conclusions:The relapse of ALL in children mainly happens in very early and early time. The main part of relapse is bone marrow, and there are many high-risk patients at initial diagnosis. The risk group at initial diagnosis, white blood cell count at initial diagnosis, relapse time, and treatment after relapse are the risk factors affecting the prognosis, and the relapse time and hematopoietic stem cell transplantation are the independent prognostic factors.