Objective To explore the pain catastrophizing (PC) level of pain in patients with multiple fractures and its influencing factors. Methods A convenience sampling method was used to investigate 156 patients with multiple fractures in the orthopedic trauma department of the First Affiliated Hospital of Nanjing Medical University. The questionnaire included a general information survey, a Digital Pain Rating Scale, PC scale, Positive and Negative Emotion Scale, and Social Rating Scale. Results The average PC score of patients with multiple fractures was (23.22±12.05), with 27 patients (17.20%) reaching the PC level. The average score of the Digital Pain Rating Scale was (6.30±1.49), the score of the Positive Emotion Scale was (27.92±6.06), the score of the Negative Emotion Scale was (23.18±7.00), and the total score of the Social Rating Scale was (27.90±4.61). The results of multiple linear regression analysis showed that pain score, negative emotion level, and social support level had predictive effects in PC among patients with multiple fractures. Conclusion The incidence of PC among patients with multiple fractures is at a moderate to high level. Patients with high pain scores, high negative emotion scores, and low social support are more likely to develop PC.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC₅₀: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC₅₀: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

Objective: To investigate the value of planned neck dissection combined with induction chemotherapy and concurrent chemoradiotherapy in regional control and the outcome of locally advanced head and neck squamous cell carcinoma. Methods: A prospective randomized controlled study totally enrolled sixty-four patients of head and neck squamous cell carcinomas(include oropharynx, hypopharynx, and larynx) in stages Ⅳa-Ⅳb with lymph node metastase was were N2-N3. All patients firstly received 2-3 cycles of induction chemotherapy(ICT), then divided into two groups randomly, according to the efficacy of ICT. Group A(the study group) received planned neck dissection(PND) and concurrent chemoradiotherapy(CCRT). Group B(the control group) received concurrent chemoradiotherapy(CCRT). The differences in clinicopathologic features, local recurrence(LR), regional recurrence(RR), disease-free survival(DFS), and overall survival(OS) between the two groups were estimated. SPSS 19.0 software was used to analyze the data. Results: Group A enrolled twenty-one patients, and group B enrolled forty-three patients.The follow-up of all patients were 4-55 months, median follow-up time was 22 months. In study group, two-year OS and DFS were 80.9% and 68.3%, respectively. In control group, two-year OS and DFS were 90.7% and 67.1%, respectively. There was no significant difference in gender(P=0.215), age(P=0.828), primary tumor site(P=0.927), LR(P=0.126), DFS(P=0.710), and OS(P=0.402) between the two groups, while the RR(χ²=5.640, P<0.05) and distant metastasis(χ²=10.363, P<0.01) showed significant differences between the two groups. Conclusion The ICT+ PND+ CCRT treatment model has benefit on regional control of locally advanced head and neck squamous cell carcinoma.

Objective: To investigate the effect of hypertensive disorder complicating pregnancy (HDCP) on the mortality and early complications of premature infants. Methods: The general clinical data of preterm infants with gestational age 24-36^{+ 6} weeks were collected from the cooperative units in the task group from January 1, 2013 to December 31, 2014.According to the severity of HDCP, the infants were divided into 4 groups: HDCP group, preeclampsia group, eclampsia group and non HDCP group, the mortality and major complications of preterm infants were compared, and the influencing factors were analyzed. Results: The mortality rate of preterm in the HDCP group was significantly higher than that of non HDCP group, and there was statistical significance (χ²=9.970, P=0.019). Eclampsia had a highest fatality rate (4.8%) in the early stage, compared with non HDCP group (2.2%), and the difference was statistically significant.Comparison of HDCP group (1.8%) and eclampsia group (3.2%) suggested that there was no statistically significant difference.The incidence of respiratory distress syndrome (RDS) in preterm in HDCP group was significantly higher than that of non HDCP group, and there was statistical significance (χ²=13.241, P=0.004). Eclampsia group showed the highest incidence (35.4%), compared with non HDCP group (16.2%), the difference was statistically significant, but compared with HDCP group (19.9%), preeclampsia group (17.1%), there was no significant diffe-rence.The incidence of bronchopulmonary dysplasia (BPD) in preterm in HDCP group was significantly higher than that of non HDCP group (χ²=9.592, P=0.022), the highest incidence showed up in eclampsia group (9.7%), compared with non HDCP group (2.0%) and HDCP group (1.7%), the difference was statistically significant.But there was no statistically significant difference, compared with preeclampsia group.As the degree of HDCP aggravated, the incidence of BPD gradually rose.There was no significant impact on necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH) and sepsis of HDCP (χ²=7.054, 7.214, 0.358, 3.852; P=0.070, 0.065, 0.949, 0.278). Considering the overall outcome of the child, that was, whether the child died or survived, he had at least one complication, and HDCP had an effect on it (χ²=15.697, P=0.001), so the incidence increased while the degree of HDCP rose gradually.After adjusting gestational age, birth weight, sex, way of delivery, placental abruption and front placenta, prenatal hormonal, gestational diabetes, neonatal asphyxia and other factors, the results displayed that HDCP was the factor leading to the death of premature baby (OR=2.159, 95%CI: 1.093-4.266), and comparison between preeclampsia and eclampsia showed no statistical difference (P=0.714, 0.389); HDCP had no significant influence on RDS, BDP, ICH, NEC, ROP and sepsis. Conclusions HDCP leads to increased risk of premature death, but also leads to the increased incidence of RDS and BPD, but it had no obvious effect on NEC, ROP, IVH, sepsis and other complications.

Objective To evaluate the feasibility of adaptive statistical iterative reconstruction-V (ASIR-V) to improve image quality in low-dose CT colonography.Methods A series of thirty artificial polyps were established by ligation in an isolated segment of porcine colon.Volume data was acquired on Revolution CT scanner (GE,USA) with High Definition scan mode and different scan parameter combinations:120 kVp with different mAs (10,30,50,70,90,100,120,140,160,180,200,220,240,260,respectively).Images were reconstructed with six different ASIR-V levels of 0 (filtered back projection,FBP),10％,30％,50％,70％ and 90％.Two radiologists were blinded to measure and analyze the objective data independently,including image noise (SD),signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR).The kappa test was used to assess interobserver agreement in subjective image quality score.ICC test was used to examine the consistency of the measurements between two observers.SD,SNR,CNR were performed for statistical analysis in different tube current and different levels of ASIR-V using variance analysis (ANOVA).Results Interobserver agreement for subjective image quality score was good with a kappa value of 0.683.The variation of the tube current(r =0.734,P =0.000) and ASIR-V level(r =0.220,P =0.044) is related to the subjective score of image quality.Under the condition of the same tube current,image quality score of 50％ ASIR-V reconstruction was the highest.Two objective data consistency is good.The differences of image noise (F =423.58,P ＜ 0.05),SNRs(F =124.26,P ＜ 0.05) and CNRs (F =1 030.17,P ＜ 0.05) of different tube current and different levels of ASIR-V reconstruction were statistically significant.In the same tube current,with increased levels of ASIR-V,image noise reduced,CNRs increased.Only in 10,120,140,160,220,240,260 mA,the differences of SNRs were statistically significant(F =8.75-31.36,P ＜ 0.05).For the same level of ASIR-V reconstruction,with the increase of tube current,the image noise decreased,SNR and CNR increased gradually.Conclusions In the CT colonography,the application of ASIR-V algorithm can significantly reduce the noise and enhance the image contrast noise ratio and improve image quality.ASIR-V algorithm with 50％ has better performance in reducing CT image noise.

Objectives To determine the risk factors of ventilator-associated pneumonia (VAP) in the pediatric intensive care unit and to explore effective strategies to reduce the morbidity of VAP. Methods A retrospective analysis was conducted on 455 children admitted into the PICU of Hunan Children's Hospital from June 2014 to June 2017. The 455 children were divided into VAP group (n=43) and non-VAP group (n=412). The incidence of VAP was identified and risk factors were compared using the logistic regression analysis via SPSS 19.0 software.Results There were 311 males and 144 females with a median age of 11 months old (29 days to 9 years and 4 months). The incidence of VAP was 9.45% (43/455). Congenital laryngeal and trachea malformation with pulmonary infection was the first reason for the occurrence of VAP (23.3%), followed by congenital heart diseases with pulmonary infection (18.6%). Via univariate analysis, types of endotracheal intubation (χ2=45.33, P<0.001), duration of mechanical ventilation (Z=1.21, P=0.034), re-intubation (χ2=20.22, P=0.004), early usage of antibiotics (χ2=4.98, P=0.026),and methods of nutritional support(χ2=10.15,P=0.006)were identified as risk factors of VAP in the pediatric intensive care unit patients (P<0.05). Based on the multivariate logistic regression analysis, the followings were all independent predictor for VAP:types of endotracheal intubation(OR=1.87,95%CI:1.48~9.75),duration of mechanical ventilation(OR=1.14, 95%CI:1.08~2.35), re-intubation (OR=3.42, 95%CI:1.26~5.57), early usage of antibiotics (OR=4.55, 95%CI:2.21~8.77). Conclusions Many risk factors were found related with the occurrence of VAP. A comprehensive analysis of the host factors and iatrogenic factors should be conducted. Rational use of antibiotics and daily assessment of extubation might help reduce the incidence of VAP.

Objective To investigate the effects of tumor necrosis factor-related ligand-1A(TL1A)on activation of T helper 9(Th9)cells of colonic tissues in chronic experimental colitis mice.Methods The chronic experimental colitis mice model was established with drinking dextran sulfate sodium salt(DSS).A total of 32 lymphocytes TL1A highly expressed mice and wild type(WT)mice were divided into WT control group, transgene control group,WT modeling group and transgene modeling group.The mice of control groups were administrated with distilled water. The mice of modeling groups received 3% DSS in drinking water discontinuously.The mice were sacrificed on 29 days after modeling.Body mass was measured,length of colon was recorded,scores of gross colon and the disease activity index(DAI)were calculated.The colonic morphological changes were observed by hematoxylin-eosin(H-E)staining.The lamina propria mononuclear cells(LPMC)were isolated and the number of Th9 cells was tested by flow cytometry.The levels of interleukin-9(IL-9)in serum and LPMC were detected by enzyme-linked immunosorbent assay(ELISA).The expressions of IL-9 protein and mRNA of the colonic tissues were measured by Western blotting and real-time polymerase chain reaction(PCR),respectively.T test and single factor analysis of variance were performed for statistical analysis.Results The percentage of body mass loss of WT modeling group was lower than that of transgene modeling group(16.2% ± 1.0% vs 18.9% ± 1.2%),and the difference was statistically significant(t=4.90, P<0.05).The scores of gross colon,DAI and pathology of transgene modeling group were all higher than those of WT modeling group(2.80 ± 0.64 vs 1.60 ± 0.31,2.55 ± 0.20 vs 1.58 ± 0.17,and 11.85 ± 0.86 vs 9.50 ± 0.79),and the differences were statistically significant(t=4.77,10.45 and 5.69,all P<0.05).The number of LPMC in transgene modeling group was higher than that of WT modeling group(3.70×106± 0.28×106vs 2.65×106± 0.32 × 106)and the difference was statistically significant(t= 6.98,P< 0.05).The percentage of Th9 in total CD4+T cells of LPMC in colonic tissues of transgene modeling group was higher than that of WT modeling group(0.54% ± 0.04% vs 0.23% ± 0.03%),and the difference was statistically significant(t= 17.54,P< 0.05).The serum IL-9 level of transgene modeling group was higher than that of WT modeling group((170.23 ± 5.69)pg/mL vs(150.62 ± 6.45)pg/mL),and the difference was statistically significant(t= 6.50,P< 0.05).The level of IL-9 secreted by LMPC of transgene modeling group was higher than that of WT modeling group((265.21 ± 8.76)pg/mL vs (237.58 ± 10.24)pg/mL),and the difference was statistically significant(t= 5.80,P< 0.05).The expressions of IL-9 protein and mRNA of transgene modeling group were higher than those of WT modeling group(1.31 ± 0.09 vs 1.18 ± 0.03,and 8.26 ± 1.13 vs 2.25 ± 0.29,respectively),and the differences were statistically significant(t=3.88 and 14.57,both P< 0.05).Conclusion TL1A high expression in lymphocytes can promote Th9 cells differentiation and IL-9 secretion which involved in the genesis of chronic experimental colitis.

Objective: To investigate the value of detecting circulating tumor cells (CTCs) in patients with local advanced head and neck squamous cell carcinoma (LAHNSCC). Methods: Twenty cases of LAHNSCC and eight healthy cases as the negative control were collected. The clinicopathological factors were evaluated. The LAHNSCC CTCs were enriched by specific antibody nanofluidic chip immunoassay using CytoSorter CTCs sorting system. LAHNSCC CTCs were identified by immunofluorescence staining. The relationships between CTCs and the clinicopathological features of LAHNSCC were analyzed. The numbers of CTCs were monitored and compared two weeks after inductive chemotherapy and at the end of the treatment. Results: CTCs were detect in 15 (75%) 20 patients with LASHNCC, with an average number of 22.4 CTCs. There was a correlation between the numbers of CTCs and age or N staging (P<0.05). Among the 15 cases with CTCs, 13 cases received inductive chemotherapy, for whom CTCs were detected again after inductive chemotherapy in all of these 13 patients, with an average number of 9.5 CTCs. Ten of the fourteen cases (71.4%) were still CTCs detected After whole treatments CTCs were detected in 14 patients, of them, 10 (71.4%) patients showed positive CTCs, with an average 1.6 CTCs. The numbers of CTCs decreased after either inductive chemotherapy or the whole treatment. The number of detected CTCs after whole treatment decreased nearly to background levels. Conclusions CTCs have a high detection rate in the peripheral blood of patients with LAHNSCC, especially in patients ≥60 years old and with ≥ N2 stage before treatment. Real-time detection of dynamic change of CTCs may assist to evaluate therapeutic effect.

Histone acetylation is a critical process in the regulation of chromatin structure and gene expression. Histone deacetylases (HDACs) remove the acetyl group, leading to chromatin condensation and transcriptional repression. HDAC inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor effects. This paper describes our work on the structural determination and structure-activity relationship (SAR) optimization of tetrahydroisoquinoline compounds as HDAC inhibitors. These compounds were tested for their ability to inhibit HDAC 1, 3, 6 and for their ability to inhibit the proliferation of a panel of cancer cell lines. Among these, compound 82 showed the greatest inhibitory activity toward HDAC 1, 3, 6 and strongly inhibited growth of the cancer cell lines, with results clearly superior to those of the reference compound, vorinostat (SAHA). Compound 82 increased the acetylation of histones H3, H4 and tubulin in a concentration-dependent manner, suggesting that it is a broad inhibitor of HDACs.