OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Objective To investigate the impact of statistical uncertainty per control point(SUpCP)on dose calculation on volumetric modulated arc therapy(VMAT)for rectum cancer,and to analyze the accuracy and efficiency of calculation.Methods 19 patients with rectum cancer undergoing radiotherapy were selected.The initial VMAT plans were generated on Monaco TPS using SUpCP=3,then changed SUpCP in the dose calculation process as follow:10 SUpCPs(1～10)for each patient,and totally190 VMAT dose distributions were obtained.For plan evaluation,Dmax,Dmean,D95%,V50,homogeneity index(HI),conformity index(CI)of the planning target volume(PTV),dissymmetric variations of bladder,small intestine and femoral head,and time calculation(Time)were analyzed.Patient specific quality assurance(PSQA),dose deviation of isocenter(ΔDISO)and passing rate of three-dimensional dose distribution(γ33,γ32,γ22)between calculated and delivered radiation doses were measured.Results AsSUpC increased,Dmax and HI of PTV,Dmax of bladder were increased,but D95%and V50 of PTV,Time,γ32 and γ22 were decreased(P<0.05).Dmax and CI of PTV,Dmean of bladder,Dmax and Dmean of small intestine and femoral head,ΔDISO and γ33 showed no statistical significance(P>0.05).When ΔDISO<1%,gamma passing rate>90%for all VMAT plan.When SUpCP<6,Dmax of PTV<110%of the prescribed dose was obtained;while SUpCP>2,time for dose calculation was less than 5 min.Conclusion For VMAT plan of rectum cancer on Monaco TPS using XVMC algorithm,3%～5%of statistical uncertainty per control point for dose calculation,and 3%2 mm or 2%2 mm gamma criteria for three-dimensional dose verification is recommended.This study provides clinical application basis for precise dose calculation of VMAT plan of rectum cancer.

Objective To observe the value of 18F-FDG PET/CT semi-quantitative parameters for predicting spread through air spaces(STAS)of clinical stage Ⅰa—Ⅲa lung adenocarcinoma.Methods Data of 85 patients with clinical stage Ⅰa—Ⅲ a lung adenocarcinoma who underwent preoperative 18F-FDG PET/CT were retrospectively analyzed.The patients were divided into positive group(n=23)or negative group(n=62)according to whether pathology showed STAS or not.Clinical and PET/CT data were compared between groups,and logistic analysis was performed to explore the efficacy of each parameter for predicting STAS.Results Significant differences of gender,carcinoma embryonic antigen,clinical stage,pathological grade,micropapillary growth and proportion were found between groups(all P＜0.05).The maximum,the mean,the peak standard uptake value(SUVmax,SUVmean,SUVpeak),as well as the maximum,the mean and the peak standard uptake value normalized by lean body mass(SULmax,SULmean,SULpeak),also the total lesion glycolysis(TLG)in positive group were all significantly higher than those in negative group(all P＜0.05).Patients'gender,proportion of micropapillary growth,SUVmax and SULmax were all independent risk factors of STAS of clinical stage Ⅰa—Ⅲa lung adenocarcinoma.The area under the curve(AUC)of the above parameters for predicting STAS was 0.666,0.912,0.839 and 0.842,respectively,and of the combination was 0.957.Conclusion 18 F-FDG PET/CT semi-quantitative parameters SUVmax and SULmax were helpful for predicting STAS of clinical stage Ⅰa—Ⅲ a lung adenocarcinoma,and further combination of gender and proportion of micropapillary growth could improve diagnostic efficacy.

Objective To compare the value of stack-of-stars-volumetric interpolated breath-hold examination(Star-VIBE)and T1-volumetric interpolated breath-hold examination(T1-VIBE)MRI for displaying peripheral lung cancer.Methods Fifty-two patients with 56 peripheral lung cancer were prospectively enrolled,and chest Star-VIBE and T1-VIBE MRI were acquired.The morphological features were observed,and the subjective scores were recorded.The maximum diameter,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of lesions were measured based on Star-VIBE and T1-VIBE MRI,respectively.Taken CT as the references,the value of Star-VIBE and T1-VIBE MRI for displaying peripheral lung cancer were compared.Results Star-VIBE MRI had higher scores for displaying spiculation sign,lobulation sign,pleural depression sign and halo sign than T1-VIBE(both P＜0.05).CNR and SNR of Star-VIBE MRI were significantly higher than those of T1-VIBE(both P＜0.001).No significant difference of the maximum diameter of lesions measured based on Star-VIBE and T1-VIBE MRI compared with CT was found,nor between Star-VIBE and T1-VIBE MRI(all P＞0.05).Conclusion Star-VIBE MRI had better value for displaying peripheral lung cancer than T1-VIBE.

At present, external treatment of traditional Chinese medicine (TCM) has been widely used in the treatment of intestinal obstruction, which is safe and effective. This study reported a case of recurrent intestinal obstruction after radiotherapy and chemotherapy for rectal cancer. After the implementation of external treatment of TCM on the basis of conventional western medicine treatment, the patient's condition improved significantly, and the patient was discharged smoothly. This case aimed to provide a reference for the diagnosis and treatment of this disease.

BACKGROUND: The biological and molecular characteristics of spread through air spaces (STAS), a newly recognized invasive mode of lung cancer, remain controversial. The aim of this study was to investigate the clinicopathological features and molecular characteristics of STAS in patients with pulmonary adenocarcinoma. METHODS: A total of 694 resected invasive non-mucinous lung adenocarcinomas diagnosed by clinicopathology from July 2019 to March 2021 in the First Affiliated Hospital of Guangzhou Medical University were collected, and the relationship between STAS and clinicopathological factors was analyzed. The state of protein expression of anaplastic lymphoma kinase (ALK) was detected by immunohistochemical method. Epidermal growth factor receptor (EGFR) was detected by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). ROS proto-oncogene 1-receptor (ROS1) was detected by reverse transcription-PCR (RT-PCR). RESULTS: A total of 344 STAS positive cases and 350 STAS negative cases were collected. By univariate analysis, STAS positivity was statistically associated with tumor maximum diameter (P<0.001), pleural invasion (P<0.001), lymphovascular invasion (P<0.001), nerve invasion (P=0.013), lymph node metastasis (P<0.001), clinical stage (P<0.001) and histological type (P<0.001). There was a statistical correlation between STAS and ALK protein expression (P=0.001). Multivariate analysis showed that STAS positive was correlated with pleural invasion (P=0.001), vascular invasion (P<0.001), lymph node metastasis (P=0.005)and ALK protein expression (P=0.032). CONCLUSIONS STAS is associated with highly aggressive biological behavior of lung adenocarcinoma, suggesting a poor prognosis.
Humans ; Lung Neoplasms/pathology* ; Lymphatic Metastasis ; Protein-Tyrosine Kinases ; Prognosis ; Neoplasm Staging ; Neoplasm Recurrence, Local/pathology* ; Proto-Oncogene Proteins ; Adenocarcinoma of Lung/pathology* ; Neoplasm Invasiveness ; Retrospective Studies

ObjectiveTo observe the effects of Fuzitang （FZT） on the proliferation of MH7A cells， the human rheumatoid arthritis synovial fibroblasts， and the expression of miR-155 and explore its anti-rheumatoid arthritis mechanism. MethodMH7A cells were cultured in vitro and divided into a blank group， high- （25 g·L^-1） and low-dose （12.5 g·L^-1） FZT groups， and a positive drug group （hydroxychloroquine， 0.006 25 g·L^-1）. The cell proliferation was detected by cell counting kit-8（CCK-8） method， and the change in the MH7A cell cycle was detected by flow cytometry. The mRNA expression of miR-155 and its downstream genes， including SH2 domain-containing inositol 5-phosphatase-1（SHIP-1）， protein kinase B 3（Akt3）， and mammalian target of rapamycin（mTOR）， was detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression of phosphatidylinositol 3-kinase （PI3K）， Akt3， and mTOR was detected by Western blot. ResultFZT in vitro in a concentration of 6.25 g·L^-1 above could inhibit the proliferation of MH7A cells in the significant dose- and time-effect manner. Compared with the blank group， the FZT groups showed increased proportions of cells in the G₂/M phase （P<0.05）， and the high-dose FZT group showed a decreased proportion of cells in the G₀/G₁ phase （P<0.05）. The arresting effect of FZT on the cell cycle was in a significant dose-effect manner. Compared with the blank group， the FZT groups showed down-regulated miR-155 and mTOR mRNA expression （P<0.05）， and the high-dose FZT group showed up-regulated SHIP1 mRNA expression and down-regulated Akt3 mRNA expression （P<0.05）. Compared with the blank group， the FZT groups showed reduced protein expression of PI3K， Akt3， and mTOR （P<0.05）. ConclusionFZT can significantly inhibit the proliferation of MH7A cells， and the mechanism is related to the promotion of the expression of SHIP-1 and down-regulation of the gene expression of the PI3K/Akt3/mTOR signaling pathway by down-regulating the expression of miR-155.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancers; however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map (cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out parbendazole as a most promising compound, which had an excellent inhibitory effect on the proliferation of HNSCC cell lines. In addition, tubulin was identified as a primary target of parbendazole, and the direct binding between them was further verified. Parbendazole was further proved as an effective tubulin polymerization inhibitor, which can block the cell cycle, cause apoptosis and prevent cell migration, and it exhibited reasonable therapeutic effect and low toxicity in the in vivo and in vitro anti-tumor evaluation. Our study repositioned an anthelmintic parbendazole to treat HNSCC, which revealed a therapeutic utility and provided a new treatment option for human cancers.

Objective:To explore the association between different paths of diabetic progression and dyslipidemia in a Nanjing adult population.Methods:From January 2017 to June 2018, 61, 098 local residents aged ≥18 years were selected from the Chronic Disease and Risk Factor Surveillance database in Nanjing using a five-stage stratified cluster random sampling method. Data were collected through interview surveys, physical measurements, and laboratory examinations. The relationship between different rates of diabetic progression and dyslipidemia was analyzed using complex weighting and multilevel models.Results:In all, 60, 283 participants were finally enrolled in the study. The weighted proportions of normal glucose regulation, pre-diabetes, and diabetes were 71.2%, 17.9%, and 10.9%, respectively. The overall weighted prevalence, awareness, treatment, and control of dyslipidemia were 29.8%, 41.6%, 28.9%, and 22.9%, respectively. The weighted proportion of patients with dyslipidemia combined with diabetes was 52.9%. The weighted prevalence of dyslipidemia in adults with normal glucose regulation, pre-diabetes, and diabetes was 24.0%, 38.8%, and 52.9%, respectively (all P<0.001). Compared to the normal glucose regulation group, subjects with pre-diabetes ( OR = 2.04, 95% CI: 1.95-2.13) or diabetes ( OR= 3.87, 95% CI: 3.66-4.10) had possibly gradually increased risks of dyslipidemia (all P<0.001). In addition, there was an increasing trend toward awareness, treatment, and control of dyslipidemia with increasing levels of glucose (all P<0.001). The weighted awareness of dyslipidemia in adults with normal glucose regulation, pre-diabetes, and diabetes was 36.3%, 42.8%, and 56.2%, respectively; the corresponding rates of treatment and control were 23.7%, 29.2%, and 43.7%, and 20.4%, 22.6%, and 30.1%, respectively. Conclusion:Diabetes and dyslipidemia have become the main chronic diseases in the Nanjing population.

Objective: To investigate the association between health literacy (HL) and health related quality of life (HRQoL) among primary and middle school students in Nanjing,and to provide a reference for improving health literacy and health related quality of life among children. Methods: In this cross sectional study, by using a multi stage rondom duster sampling method,a total of 4 388 primary (4-6), junior (grades 7-9) and senior (grades 10-12) high school students were randomly selected in Nanjing during May and June of 2018. HRQoL was measured as continuous variable with the validated Chinese version of Child Health Utility 9D (CHU9D CHN); the relationship between health literacy level and HRQoL was examined using mixed effect linear regression models and reported as mean difference ( MD ) and 95% confidence interval( CI ). Results: There were 85.8% participants who obtained adequate health literacy level, while the mean score of CHU9D CHN was (0.78±0.17) for overall participants. After control for potential confounding factors and class level clustering effects, participants who self reported adequate HL recorded an increased HRQoL scores of 0.08 (95% CI =0.06-0.10) units relative to those self reporting inadequate HL. According to the stratified analysis of students gender, school type and place of residence, the results show that after adjusting the relevant confounding factors and the aggregation of class level, compared with the students without health literacy, the score of health related quality of life of those with health literacy increased significantly. Conclusion Health literacy of primary school students in Nanjing is positively related to health related life qualities.Therefore,there is a need to promote student s health related quality of life through health literacy.