OBJECTIVE To obtain stronger cytotoxic activity of panaxadiol derivatives. METHODS The 3-amino panaxadiol was prepared by the bioelectronic isosteric principle, and then 18 derivatives of cinnamic acid, NO donor and other types of panaxadiol derivatives were synthesized, among them, 12 compounds had not been reported in the literature, and their structures had been confirmed by 1H-NMR, 13C-NMR and mass spectrometry. These compounds were evaluated for their cytotoxic activity by MTS assay against human leukemia cell line HL-60, liver cancer cell line SMMC-7721, lung cancer cell line A-549, breast cancer cell line MCF-7, and colon cancer cell line SW480. RESULTS These results showed that compounds 6c, 7 as well as 7j exhibited potent inhibitory activities against all five tumor cells, especially the IC50 values of compound 7 against HL-60 and SMMC-7721cells were 3.41 and 4.51 μmol·L−1, respectively. It was significantly superior to panaxadiol in cytotoxicity. CONCLUSION These results show that 7 and 7j can be used as promising lead compounds for further research.

Objective: To explore the changes in ribosomal DNA copy number in peripheral blood among patients with pneumoconiosis and its influencing factors, so as to provide insights into prevention and treatment of pneumoconiosis. Methods: Eighty-eight patients with pneumoconiosis who visited a designated hospital and 71 community residents with no history of pneumoconiosis or dust exposure were selected as the pneumoconiosis group and control group, and age, smoking history, drinking history and cumulative years of exposure to dust were collected through questionnaire surveys. The copy number of 45S rDNA and 5S rDNA was detected using real-time fluorescence quantitative PCR, and the differences between the two groups were compared. Factors affecting the copy number of 45S rDNA and 5S rDNA were identified by a multiple linear regression model. Results: The pneumoconiosis group had a median age of 56.00 (interquartile range, 15.25) and a mean cumulative dust exposure duration of (12.40±8.08) years, with 56.82% smoking and 62.50% drinking. The control group had a median age of 64.00 (interquartile range, 37.00) years, with 32.39% smoking and 26.76% drinking. The median copy number of 45S rDNA in the pneumoconiosis group was 1.29 (interquartile range, 0.59), which was lower than 2.10 (interquartile range, 1.88) in the control group; the median copy number of 5S rDNA in the pneumoconiosis group was 5.33 (interquartile range, 0.85), which was higher than 4.66 (1.34) in the control group (both P<0.05). Multiple linear regression analysis identified age (β=-0.034) and pneumoconiosis (β=-1.595) as factors affecting 45S rDNA copy number, age (β=-0.013) as a factor affecting 5S rDNA copy number, and age (β=0.018) as a factor affecting 5S rDNA copy number in the pneumoconiosis group (all P<0.05). Conclusions Compared with community residents with no history of pneumoconiosis or dust exposure, the copy number of 45S rDNA in peripheral blood among patients with pneumoconiosis is reduced and the copy number of 5S rDNA is increased.

The cognitive impairment of diabetes mellitus type 2(T2DM)is closely related to neurovascular coupling(NVC)changes,but the exact mechanism remains unclear.Functional MRI(fMRI)technology were able to jointly analyze NVC changes of T2DM,providing new ideas for revealing the mechanism of cognitive dysfunction caused by T2DM.The progresses of fMRI for exploring NVC changes in T2DM were reviewed in this article.

Objective To isolate and culture neural crest cells(NCCs)from lung tissue of mice and to identify the characteristics of the cells in order to provide a new cell model for studying lung injury and injure repair.Methods The mT/mG dual-fluorescence reporter mice and Wnt1-Cre transgenic mice were hybridized,and mT/mG;Wnt1-Cre transgenic mice were screened to obtain enhanced green fluorescent protein(EGFP)permanently labeled NCCs.Cell suspension of mouse lung tissue was prepared by enzymolysis.EGFP+cells(namely NCCs)were har-vested by flow cytometry.Primary culture was performed with DMEM/F12 culture medium optimized in the labora-tory,NCCs was characterized by immunofluorescence microscopy.Then NCCs differentiation was directed by mouse bone marrow mesenchymal stem cells osteogenic induction.Results The mT/mG of EGFP permanently labeled NCCs was successfully obtained by hybridization and high-purity NCCs were isolated from Wnt1-Cre transgenic mice lung tissue.They can be cultured in vitro and with spindle morphology which was,similar to fibroblast adherent proliferation.NCCs expressed the neural crest stem cell marker Sox10 and induced to differentiate into osteoblasts.Conclusions NCCs isolated and cultured from lung tissue of mT/mG;Wnt1-Cre transgenic mice show stable prolif-eration and have the characteristics of neural crest stem cells,which may function as a potential cell model for re-search on lung tissue injury and the mechanism of repair.

Objective: To establish a convenient non-invasive tracheal perfusion method for constructing a mouse model of silicosis-induced pulmonary fibrosis. Methods: The specific pathogen-free C57BL/6 mice were randomly divided into control group and model group, with 15 mice in each group. After anesthesia, a 22G arteriovenous indwelling needle was used to inset into the trachea through the mice's mouth. The model group mice were perfused with 0.1 mL of silica suspension with a mass concentration of 25 g/L, and the mice in the control group were perfused with an equal volume of 0.9% sodium chloride solution. On the 7th, 14th, and 30th day after modeling, the body weight of the mice was measured, and the lung tissue morphology and pathological changes were observed. The expression of α-smooth muscle actin (α-SMA) and collagen type 1 alpha 1 (COL1A1) protein in lung tissue of mice was detected by immunofluorescence on the 30th day after modeling. Results: There was no death of mice in the two groups during the experiment. There was no significant difference in body weight between the two groups (P>0.05). The lung tissues of the mice in the model group were pinkish-gray and uneven in color on the 7th and 14th days after dust exposure. On the 30th day after dust exposure, the lung tissue of the mice in the model group was gray and hard, and unevenly distributed silicon nodules were visible by the naked eyes. The histopathology results of lung tissue showed that compared with the mice in control group, the model group mice exhibited persistent aggravation of pulmonary inflammation, thickening of alveolar septum, infiltration of inflammatory cells gradually clustering into clumps, and an increasing number of fibrous foci.On the 30th day after dust exposure, the relative expression of α-SMA and COL1A1 proteins in the lung of the model group was higher than those in the control group (median： 72.59 vs 5.91, 35.62 vs 10.07, both P<0.05). Conclusion: The method of tracheal perfusion silica suspension of mice using 22G arteriovenous indwelling needle can successfully construct an animal model of silicosis fibrosis. This method is convenient, safe and effective, and is worth promoting.

Objective:To compare the efficacy and safety between WangShiBaoChiWan and mosapride in the treatment of functional dyspepsia (FD).Methods:From September 2019 to September 2020, patients with postprandial fullness and early satiation who met the Rome Ⅳ criteria for FD diagnosis were enrolled from 15 hospitals, including the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), Beijing Traditional Chinese Medicine Hospital Affiliated to Capital Medical College. The subjects were randomly divided into WangShiBaoChiWan (experimental) group and mosapride (control) group in the ratio of 1∶1. The treatment regimens were WangShiBaoChiWan+ mosapride simulator, WangShiBaoChiWan simulator+ mosapride, respectively with a treatment period of 2 weeks. The primary efficacy outcome was the improvement rates of main symptoms before and after treatment, the secondary efficacy primary efficacy outcome was the total clinical effective rate and the change of the single symptom score. And the safety indicator included adverse events. Independent sample t-test, paired t-test and chi-square test were used for statistical analysis. Results:A total of 251 FD patients were enrolled in the full analysis set, including 124 in the experimental group and 127 in the control group; 241 FD patients were in the per-protocol analysis set, including 117 in the experimental group and 124 in the control group. The analysis of per-protocol analysis set showed that the improvement rates of the main symptoms of the experimental group and the control group were (66±29)% and (60±30)%, respectively, and the difference was not statistically significant ( P>0.05). The improvement rate of the main symptoms of the experimental group reached 117% of that of the control group, which exceeded the expected non-inferiority standard of 80%. The total clinical effective rates of the experimental group and the control group were 76.07% (89/117) and 75.81% (94/124), respectively, and the difference was not statistically significant ( P>0.05). The results of full analysis set showed that the incidence of adverse events of the experimental group and the control group was 1.62% (2/124) and 1.57% (2/127), respectively, and the difference was not statistically significant ( P>0.05). There were no serious adverse events in the two groups. Conclusion:The improvement rate of the main symptoms of WangShiBaoChiWan is not inferior to that of mosapride in the treatment of FD, and it has good safety.

Objective:To understand the real physical and mental experience of family caregivers for centenarians in the long-term care process and to provide a basis for alleviating the pressure of caregivers and reducing social burdens.Methods:Using the purposive sampling method, family caregivers of centenarians in Rugao City of Jiangsu Province from April to June 2020 were selected as the research objects.The phenomenological research method in qualitative research was used to conduct in-depth interviews with family caregivers of centenarians. The content analysis method was used to analyze the data, sort out and extract the theme.Results:After comparative analysis, the physical and mental experience of family caregivers of centenarians revealed three themes. including grateful heart, diversified care pressure and social support needs to be further improved.Conclusions:Long-term family care work has a negative effect on the life of the centenarian family caregivers. The government, community and social workers should take the initiative to intervene and provide multi-channel support to reduce the physical and mental stress of the family caregivers and improve the satisfaction and quality of life of both caregivers and centenarians.

Objective:To explore the clinical value of "hydration therapy" in the treatment of severe acute paraquat poisoning (APP).Methods:A prospective historical control observation was conducted. Fifty-eight patients with severe APP admitted to Shouguang People's Hospital Affiliated to Weifang Medical College from February 2014 to June 2019 were enrolled. Twenty-six patients admitted before May 10th, 2016 were enrolled in the standard treatment group. After being admitted to intensive care unit (ICU) from the department of emergency, patients in the standard treatment group were immediately given standard treatment such as repeated gastric lavage, catharsis, adsorption of poison by activated carbon or montmorillonite powder, drug treatment and blood purification. From May 10th, 2016, 32 patients were enrolled in the intensive treatment group. On the basis of standard treatment, "hydration therapy" was carried out, that was, 0.9% NaCl and/or 5% glucose injection were used for continuous intravenous infusion throughout the day, so as to ensure that the total amount of fluid infusion per day reached 200 mL/kg within 48-72 hours after ICU admission. At the same time, furosemide was used to strengthen diuresis to ensure the balance of water and electrolyte. If heart failure or acute pulmonary interstitial edema occurred during the treatment, "hydration therapy" should be stopped immediately. Six months after treatment, all patients were followed up. The patients with normal activity, no complaints of discomfort and no damage of heart, lung, liver, kidney and other organs were regarded as cured. The therapeutic effect of "hydration therapy" was evaluated.Results:There was no significant difference in gender, age, dosage or time from taking poison to ICU between the two groups. In the intensive treatment group, 32 patients did not appear heart failure during continuous rehydration treatment. Follow-up after 6 months showed that the overall cure rate in the intensive treatment group was significantly higher than that in the standard treatment group [59.4% (19/32) vs. 19.2% (5/26), P < 0.05]. In the 6-month follow-up, there was no significant difference in age or time from taking poison to ICU between the two groups, but the dosage in the intensive treatment group was significantly higher than that in the standard treatment group (mL: 54.06±26.03 vs. 23.00±4.47, P < 0.05). After 6 months of follow-up, chest CT showed that the lesions of pulmonary fibrosis of cured patients in both group gradually reduced with time, not completely progressive and irreversible. Conclusion:"Hydration therapy" with intensive diuresis can significantly improve the rescue success rate of patients with severe APP.

Objective To analyze the characteristics and correlated factors of attempted suicide among psychological aid hotline callers,and provide a reference for suicide prevention and intervention to the domestic psychological aid hotlines.Methods From September,2010 to August,2015,1 299 callers who had the database of attempted suicide among hotline callers were collected.During the calling,the callers were interviewed on their attempted suicides,depression and 10 correlated factors associated with caller's suicidal behaviors.Results Among 1 299 callers who received assessment of suicidal behavior relates factors,361 (27.8％) had evaluated of current suicidal ideation or behavior,223 (17.2％) had history of prior suicidal attempts.There was no significant difference in the incidence of suicide attempts among different gender,age and occupation.1 024 (78.8％) had symptoms of mental illness,794 (61.1％) had symptoms of anxiety,708 (54.5％) had symptoms of depression,864(66.5％) had concomitant two or more symptoms.Compared the caller's occurrence rate of suicidal attempter between single depression and concomitant other symptoms,the results found single depression and concomitant anxiety,concomitant obsession,concomitant panic and concomitant fear were statistically significant.Multiple logistic regression analysis showed that high depression emotion (β=O.389,OR=1.48,95％CI=1.08-2.02),the history of prior attempted suicide (3=0.487,OR=1.63,95％CI=1.19-2.22) and high hopelessness (β=0.618,OR=1.86,95％CI=1.32-2.60) were associated with the caller of ever attempted suicide behaviors.Conclusion Among the callers with attempted suicide,in order to improve the effectiveness of hotline prevention and invention,the psychological consultant should focus on the evaluation of concomitant mental symptoms,high depression emotion,history of prior attempted suicide and hopelessness.

Objective: To evaluate the value of computed tomography (CT) multi-planner reconstruction (MPR)in the treatment of lung cancer with percutaneous argon-helium cryoablation.Method:A total of 66 patients with stage T2 or T3 non-small cell lung can-cer who had complete follow-up data were treated with percutaneous argon-helium cryoablation with conventional axial CT(conven-tional group)or MPR guidance(MPR group)between January 2013 and 2016.There were 31 patients in the conventional group and 35 in the MPR group.The total number of punctures,the total time of operation,and the incidence of complications,tumor residual rates,and local control rates were compared between the two groups.Results:When the number of needles was the same,the aver-age number of punctures and puncture errors in the two groups were significantly lower in the MPR group than in the conventional group(P<0.05).Comparing the average operation time,there was no statistical difference between the MPR group and the conven-tional scan group(P>0.05).The incidence of postoperative complications was significantly lower in the MPR group than in the conven-tional scan group.Among them,the incidence of puncture combined hemorrhage was 1.52% vs.13.64%,and pneumothorax second-ary to puncture was 3.03% vs.19.70%(P<0.05).During the follow-up period to 12 months after surgery,the therapeutic benefit indica-tors such as local residual rate and total effective rate in the MPR group were also significantly better than those in the conventional group,which were 1.52% vs.10.61 and 51.52% vs.36.36%(P<0.05),respectively.Conclusions:Using MPR technology to guide percuta-neous argon-helium cryoablation treatment for lung cancer confers a small puncture error,low incidence of complications,and signifi-cant treatment benefits.This method is worthy of clinical promotion.