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.

A Clinical pharmacist was fully involved in the anticoagulation drug treatment management process of a 104-year-old patient with a large area of cerebral infarction combined with chronic kidney disease stage Ⅴ and secondary deep vein thrombosis.After the patient was diagnosed with deep vein thrombosis,the clinical pharmacist comprehensively analyzed the patient's super-advanced age,history of atrial fibrillation,large area of cerebral infarction,extremely poor kidney function,deep vein thrombosis,and high bleeding risk indicated by the HAS-BLED score.They worked with the clinical doctor to develop an individualized anticoagulation treatment strategy for the patient.At the beginning of the treatment,warfarin was given to the patient at a daily dose of 1.25 mg,and the patient's coagulation indicators and kidney function were dynamically rechecked.The patient's blood creatinine level did not show significant changes throughout the anticoagulation treatment process.On the 8th day of medication,the patient's INR was 2.47,and the clinical pharmacist suggested adjusting the Warfarin to an alternate-day dose of 1.25 mg and 0.625 mg.Subsequently,the patient's INR was 2.41,and the condition improved,leading to discharge.Throughout the anticoagulation drug management process,the clinical pharmacist participated in the clinical decision-making for anticoagulant drug selection,provided professional medication guidance,and pharmacological monitoring to ensure the safe clinical use of drugs for special populations.

To analyze the long-term stability of the output dose of the medical linear accelerator VitalBeam based on Mechanical Performance Check(MPC)system.500 daily self-test data of the medical linear accelerator VitalBeam from January 2021 to December 2023 were collected,and the change trend and stability status of dose output deviation were analyzed.Through MPC detection and data analysis,the 6MV X-Ray in radiation dose output change was(0.53±0.85)%,the ray uniformity change was(0.54±0.15)%,and the ray center offset change was(0.15±0.07)mm,all of which were within the allowable range of error.The 6 MV photon beam dose output of the medical linear accelerator is stable and reliable,which meets the needs of clinical treatment,and the MPC detection can be used for the daily inspection and quality control of the accelerator.

Objective:To evaluate the effectiveness and safety of concurrent chemoradiotherapy combined with nimotuzumab in the treatment of patients with inoperable esophageal squamous cell carcinoma (ESCC).Methods:A retrospective analysis was conducted on the clinical data of 503 patients with inoperable ESCC who underwent concurrent chemoradiotherapy in the Department of Radiation Oncology, Changzhou No. 2 People′s Hospital Affiliated to Nanjing Medical University and Department of Radiation Oncology, Affiliated Hospital of Jiangnan University from 2014 to 2020. Among these patients, 69 received concurrent chemoradiotherapy combined with nimotuzumab (the combined therapy group) and 434 received concurrent chemoradiotherapy alone (the concurrent chemoradiotherapy group). Patients of both groups were matched at a ratio of 1∶2 using the propensity score matching (PSM) method. As a result, 168 patients were determined for clinical analysis, including 61 in the combined therapy group and 107 in the concurrent chemoradiotherapy group. The short-term efficacy and adverse reactions of both groups were compared. The overall survival (OS) curves and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method for the Log-rank test.Results:The two groups showed no statistical difference ( P > 0.05) in clinical baseline characteristics after the PSM. The objective response rate (ORR) of the combined therapy group was significantly higher than that of the concurrent chemoradiotherapy group with statistically significant differences (85.2% vs. 71.0%, χ2 = 4.33, P = 0.037). There was no statistical difference (98.4% vs. 91.6%, P > 0.05) in the disease control rate (DCR) between the two groups. The combined therapy group had median PFS of 28.07 months and 1-, 3-, and 5-year PFS ratios of 78.2%, 37.5% and 29.1%, respectively. The concurrent chemoradiotherapy group had mPFS of 19.54 months and 1-, 3-, and 5-year PFS ratios of 72.9%, 28.3% and 21.3%, respectively. Both groups showed statistically significant differences in PFS ( χ2 = 4.49, P = 0.034). The combined group had median OS of 34.93 months and 1-, 3-, and 5-year OS ratios of 88.5%, 46.8% and 37.4%, respectively. The concurrent chemoradiotherapy group had mOS of 24.30 months and 1-, 3-, and 5-year OS ratios of 81.3%, 35.2% and 28.0%, respectively. Both groups showed statistically significant differences in OS (χ 2= 5.11, P = 0.024), but did not show statistical differences ( P > 0.05) in the severity degree of each adverse effect during the treatment. Conclusions:Concurrent chemoradiotherapy combined with nimotuzumab can improve the ORR and prolong the PFS and OS of patients with inoperable ESCC compared with concurrent chemoradiotherapy alone. Furthermore, combining with nimotuzumab does not increase adverse effects and can be tolerated by patients with high safety.

Objective:To evaluate the effect of niraparib, the poly (ADP-ribose) polymerase (PARP) inhibitor, on the radiosensitivity of esophageal squamous cell carcinoma (ESCC) and to preliminarily investigate its mechanism.Methods:Human esophageal squamous cell carcinoma cells ECA-109 and KYSE-150 were divided into the control, niraparib, single irradiation, combined (niraparib+irradiation) groups. Cell proliferation was measured by CCK-8 assay. The changes of cell survival rate were detected by colony formation assay. The changes of cell cycle and apoptosis were analyzed by flow cytometry. The number of γH2AX foci was detected by immunofluorescence, and the expression levels of PARP-1, cleaved-PARP, RAD51, mitogen-activated protein kinase (MAPK) [extracellular signal-regulated kinase 1 and 2 (ERK1/2) ] and p-MAPK (ERK1/2) proteins were determined by Western blot. All data were expressed as Mean±SD. Data between two groups conforming to normal distribution through the normality test were subject to independent sample t-test and multiple groups were analyzed using one-way ANOVA. Results:In human ESCC cells ECA-109 and KYSE-150, the proliferation of ESCC cells was significantly inhibited by niraparib combined with irradiation, and the values of average lethal dose (D 0), quasi-threshould dose(D q), survival fraction after 2 Gy irradiation (SF 2) in the combined group were decreased compared with those in the single irradiation group. The effect of irradiation alone on apoptosis of ECA-109 and KYSE-150 cells was limited. Compared to single irradiation group, irradiation combined with niraparib further increased the apoptosis rate in ESCC cells ( P=0.015, P=0.006). In ECA-109 cells, G 2/M phase arrest was significantly increased in combined group compared with irradiation alone group ( P<0.001). In ECA-109 cells, the number of γH2AX foci in combined group was higher than that in the single irradiation group after 2 h, and showed a significantly slower decay of γH2AX foci ( P<0.001). Moreover, niraparib combined with irradiation enhanced the radiation-induced cleavage of PARP-1 and down-regulated the expression of Rad51 and p-MAPK(ERK1/2). Conclusion:Niraparib can increase the radiosensitivity of esophageal cancer cells by inhibiting cell proliferation, promoting cell apoptosis, inhibiting the repair of DNA damage and regulating the MARK-ERK signaling pathway.

Objective:To study the effects of poly adenosine diphosphate ribose polymerase (PARP) inhibitors niraparib and pamiparib on the radiosensitivity of breast cancer cell lines MCF-7 and MDA-MB-436, and to explore its mechanism.Methods:MCF-7 and MDA-MB-436 cells were divided into control group, niraparib group, pamiparib group, radiation group, combination group treated with niraparib and radiation, and combination group treated with pamiparib and radiation, respectively. The effects of drugs on cell proliferation and radiosensitivity were measured by CCK-8 assay and colony formation assay, respectively. The effect of drugs combined with radiation on cell cycle and apoptosis were detected by flow cytometry. Immunofluorescence method was used to detect the changes of γ-H2AX focal number of cells. The expressions of FANCG, Bax and Bcl-2 mRNA and protein were detected by qPCR and Western blot, respectively.Results:Both niraparib and pamiparib inhibited the proliferation of breast cancer cells MCF-7 and MDA-MB-436 in a time-dose dependent manner. With the increase of irradiation dose, D0, Dq, SF2 value of MCF-7 and MDA-MB-436 cells decreased, and SER D0 and SER Dq value increased. Compared with control group, the percentages of cells in G 2/M phase were increased ( tMCF-7=41.66, 44.08, P<0.05; t436=24.69, 18.91, P<0.05), the percentage of cells in G 0/G 1 phase were decreased ( tMCF-7=8.67, 29.61, P<0.05; t436=26.39, 29.12, P<0.05), and the cell apoptosis rate was significantly increased ( tMCF-7=11.17, 11.71, P<0.05; t436=42.68, 15.89, P<0.05) in the combination group. Compared with control group, the number of γ-H2AX foci of MCF-7 cells in the radiation group and combination group treated with niraparib and radiation increased significantly at 2 h after irradiation ( t=8.89, 21.72, P<0.05). At 24 h after irradiation, the number of γ-H2AX foci basically returned to normal level in the radiation group but remained at a higher level in the combination group ( t=8.82, P<0.05). Compared with control group, the expressions of FANCG and Bcl-2 mRNA decreased ( tFANCG=14.07, P<0.05; tBcl-2=29.21, P<0.05), the expression of Bax mRNA increased ( t=8.90, P<0.05), and the expression of FANCG and Bcl-2 proteins decreased ( tFANCG=7.09, P<0.05; tBcl-2=10.24, P<0.05), while the expression of Bax protein increased ( t=2.90, P<0.05) in the combination group. Conclusions:PARP inhibitors niraparib and pamiparib can increase the radiosensitivity of breast cancer MCF-7 and MDA-MB-436 cells probably through down-regulating the expression of FANCG in FA-BRCA pathway, up-regulating apoptosis-related genes and inhibiting DNA damage repair.

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.

ObjectiveBy using bibliometrics and scientific knowledge mapping technology， this study systematically combs and visually analyzes the research hotspots， frontiers and trends of infectious disease prevention and control in China in the past 30 years， summarizes the research direction in this field， combs the knowledge structure， and provides guidance and reference for subsequent research. MethodsThe databases of CNKI and Wanfang were searched by （"infectious diseases" or " communicable diseases"） and "prevention and control" not "chronic diseases"， The bibliometric software VOSviewer 1.68 and CiteSpace 5.8.3 were used to analyze the co-occurrence network of scientific knowledge maps from the keywords， emerging words， research authors， institutions and other aspects， and summarized the research hotspots， frontiers and trends in the field of infectious disease prevention and control in China. ResultsA total of 10 777 literatures were retrieved， and 7 676 literatures were included after screening. From the perspective of research trend， the number of published literatures in the field of infectious disease prevention and control in China showed an overall upward trend， and the number of studies was closely related to the outbreak of infectious diseases. The Chinese Center for Disease Control and Prevention has played a leading role in the research. In terms of researchers' cooperation， Hao Mo， Li Chengyue， Wang Ying and others from Fudan University were the main researchers' cooperation teams. Tu Wenxiao， Meng Ling and Xiang Nijuan from the Chinese Center for Disease Control and Prevention were the main researchers. Wang Quanyi， Li Xinyu， Wang Xiaoli from the Beijing Center for Disease Control and Prevention were the main researchers' research teams. Yang Zhicong， Li Meixia， Luo Lei and other research teams from Guangzhou Center for Disease Control and Prevention have formed a relatively obvious cooperation network. Analysis of the keyword cluster atlas showed that the articles related to the prevention and control of infectious diseases mainly were focused on the epidemiology of new coronavirus infection （new infectious diseases）， school infectious diseases， common infectious diseases， and the related research of vector infectious diseases. The analysis of salient words indicated the research focus and trend change in different time periods. At present， the research focus and frontier in the field of infectious diseases are mainly concentrated in the field of prevention and control of new infectious diseases， such as the monitoring， early warning， reporting， emergency management， laws and regulations of the new coronavirus infection. ConclusionOur country attaches great importance to the prevention and control of infectious diseases， with extensive and in-depth research hotspots. In particular， research on emerging infectious diseases has developed rapidly and achieved remarkable results. With the application of molecular biology， big data， AI and other technologies in the field of infectious disease prevention and control， China's infectious disease prevention and control capabilities will be greatly improved. At the same time， it is necessary to strengthen the linkage between universities， disease control institutions， and medical institutions， and establish and improve a long-term normal prevention and control mechanism.

Objective To analyze the characteristics, trend and influencing factors of occupational pneumoconiosis in Guizhou, and to provide reference for the prevention and treatment of occupational pneumoconiosis. Methods A total of 1 974 mining patients in Guizhou province were selected from 2019-2020 by stratified sampling survey method. According to whether they were accompanied by occupational pneumoconiosis, they were divided into control group (n=1218) and experimental group (n=756) to analyze the morbidity characteristics, changing trend and influencing factors of occupational pneumoconiosis. Results From 2019 to 2020, 756 (38.30%) of the 1974 mining people in Guizhou suffered from occupational pneumoconiosis, including 602 (79.63%) in stage I, 86 (11.38%) in Stage II, and 68 (8.99%) in stage III. The average age was (57.36±6.89) years, and the average length of service was (15.56±4.47) years. The onset age was mainly from 50 to 69 years, and the difference was statistically significant (χ²=8.214，P<0.05). Pneumoconiosis was the main disease in 613 cases (81.08%), followed by silicosis in 85 cases (11.24%), the difference was statistically significant (χ²=25.429，P<0.05). The incidence trend of coal worker's pneumoconiosis was stable, while the incidence of silicosis in 2020 was higher than that in 2019 (χ²=8.797，P<0.05). There was significant difference in smoking status among patients with different stages (χ²=27.212，P<0.05). There were significant differences in age, sex, smoking ratio, length of exposure to dust and complications between the two groups (P<0.05). Logistic regression analysis showed that age, length of dust exposure and complications were independent risk factors for occupational pneumoconiosis (P<0.05). Conclusion The occupational pneumoconiosis in Guizhou area is mainly male, the high incidence age is 50-69 years old, the development is stable, while the incidence of silicosis is increasing in recent years, among which the dust exposure age, age and complications are the high risk factors of occupational pneumoconiosis.

Objective:To investigate the serum thyroglobulin (Tg) levels of women in early pregnancy in Dali City, Yunnan Province, and provide a scientific basis for evaluation of individual iodine nutrition of early pregnant women in this area.Methods:Dali City, Yunnan Province was divided into 5 sampling areas according to east, west, south, north and middle. One township (town) was selected from each area, and at least 20 women in early pregnancy were selected from each township (town) as survey subjects. General condition and medical history of all subjects were collected, and random urine samples and fasting venous blood samples were collected for determination of urinary iodine and thyroid function indexes, and a portable ultrasound machine was used for thyroid ultrasonography. After excluding the patients with a history of thyroid disease and abnormal thyroid function, the level of Tg in the included early pregnant women was analyzed.Results:A total of 120 women in early pregnancy were investigated, aged from 19 to 40 years. Among them, 61 cases came from urban areas and 59 were from rural areas. The median urinary iodine was 156.54 μg/L, which was at the appropriate level of iodine nutrition. A total of 102 women with normal thyroid function in early pregnancy were included, and the Tg level was 11.56 (6.67, 15.27) ng/ml. Among them, 58 cases were in urban areas and 44 cases were in rural areas. There was no significant difference in serum Tg levels between rural and urban women in early pregnancy ( U = 1 362.50, P = 0.559). Conclusion:The serum Tg level of women in early pregnancy in Dali City can provide a reference for evaluation of individual iodine nutrition of relevant populations in this area.