The impacts of patient mistreatment on healthcare workers' role behaviors: a study in Chinese Fangcang shelter hospitals.

BACKGROUND: Fangcang shelter hospitals have played an important role in the battle against the COVID-19 epidemic in China. Patients' verbal and physical attacks on medical workforce are prone to occur in such hospitals. This study explored the impacts of patient mistreatment on healthcare workers' role behaviors (service performance and patient-oriented organizational citizenship behavior). METHODS: We examined the influence of patient mistreatment on service performance and patient-oriented organizational citizenship behavior, as well as the mediating effect of emotional exhaustion and the moderating effect of displaced aggression by patients, using hierarchical linear regression and conditional process analysis. RESULTS: Patient mistreatment was positively associated with emotional exhaustion among healthcare workers, while emotional exhaustion was negatively associated with service performance and patient-oriented organizational citizenship behavior. Mediation analysis revealed that emotional exhaustion mediated the association between patient mistreatment and both types of role behaviors. Moderated mediation analysis found that the mediation effect was weaker when the displaced aggression by patients was high. CONCLUSIONS: The findings clarified the relationship among patient mistreatment, emotional exhaustion, service performance, and patient-oriented organizational citizenship behavior. Additional assistance should be provided to healthcare workers dealing with patient mistreatment. Displaced aggression by patients attenuates the positive effects of patient mistreatment on the emotional exhaustion of healthcare workers. Our findings reveal the mechanism and boundary conditions of patient mistreatment affecting healthcare workers' service performance and patient-oriented organizational citizenship behavior.

Molecular mechanism of palmitic acid and its derivatives in tumor progression.

Palmitic acid (PA) is a saturated fatty acid commonly found in coconut oil and palm oil. It serves as an energy source for the body and plays a role in the structure and function of cell membranes. Beyond its industrial applications, PA has gained attention for its potential therapeutic properties. Modern pharmacological studies have demonstrated that PA exhibits anti-inflammatory, antioxidant, and immune-enhancing effects. In recent years, PA has emerged as a promising anti-tumor agent with demonstrated efficacy against various malignancies including gastric cancer, liver cancer, cervical cancer, breast cancer, and colorectal cancer. Its anti-tumor effects encompass inducing apoptosis in tumor cells, inhibiting tumor cell proliferation, suppressing metastasis and invasion, enhancing sensitivity to chemotherapy, and improving immune function. The main anticancer mechanism of palmitic acid (PA) involves the induction of cell apoptosis through the mitochondrial pathway, facilitated by the promotion of intracellular reactive oxygen species (ROS) generation. PA also exhibits interference with the cancer cell cycle, leading to cell cycle arrest predominantly in the G1 phase. Moreover, PA induces programmed cell autophagy death, inhibits cell migration, invasion, and angiogenesis, and synergistically enhances the efficacy of chemotherapy drugs while reducing adverse reactions. PA acts on various intracellular and extracellular targets, modulating tumor cell signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), endoplasmic reticulum (ER), B Cell Lymphoma-2 (Bcl-2), P53, and other signaling pathways. Furthermore, derivatives of PA play a significant regulatory role in tumor resistance processes. This paper provides a comprehensive review of recent studies investigating the anti-tumor effects of PA. It summarizes the underlying mechanisms through which PA exerts its anti-tumor effects, aiming to inspire new perspectives for the treatment of malignant tumors in clinical settings and the development of novel anti-cancer drugs.

High-resolution computed tomography features of asbestosis versus fibrotic hypersensitivity pneumonitis: an observational study.

BACKGROUND: Asbestosis and fibrotic hypersensitivity pneumonitis (FHP) share the pathogenetic mechanisms induced bronchiolocentric fibrotic process secondary to inhalation exposure. Under the occupational and environmental mixed exposures, asbestosis and FHP are needed to make the differential diagnoses on high-resolution computed tomography (HRCT), especially in the countries still using asbestos. The study aimed to analyze the HRCT features of asbestosis versus FHP. METHODS: The patients with asbestosis or with HP were sequentially recruited in this comparative study at Beijing Chaoyang Hospital between January 2006 and December 2016. Patients' clinical data were obtained from a predesigned charts. The international classification of HRCT for occupational and environmental respiratory diseases was used to categorize chest imaging findings in patients. The calculation of test statistics was used to compare the imaging features of asbestosis and FHP. RESULTS: 341 patients with asbestosis and 158 patients with HP were sequentially recruited, among which 204 patients with asbestosis and 74 patients with FHP were eligible for data analysis. Patients with asbestosis were older and had a longer latent period until disease manifestation than those with FHP. Asbestosis was characterized by irregular and/or linear opacities, with lower lung preponderance, accompanied by ground-glass opacities and mosaic attenuation. Notably, 98.5% of patients with asbestosis showed benign pleural abnormalities, and 39.7% of these patients had diffuse pleural thickening with parenchymal bands and/or rounded atelectasis. Abnormalities of the mediastinal and diaphragmatic pleura were observed only in cases of asbestosis, and this finding showed high specificity for the diagnosis for asbestosis compared with that for FHP. Subpleural dots or diaphragmatic pleural abnormalities showed moderate sensitivity and high specificity for diagnosis of asbestosis compared with that for FHP. Interobserver reliability was good for evaluation of imaging findings including honeycombing, pleural calcification, lymphadenectasis, and lymph node calcification. CONCLUSIONS: HRCT-based imaging findings can distinguish between asbestosis and FHP to a certain extent, particularly with regard to subpleural dots and diaphragmatic pleural abnormalities that characterize the former.

A Retrospective Study of the Safety and Efficacy of Endoscopic Radiofrequency Therapy Under Direct Vision in 59 Patients with Gastroesophageal Reflux Disease from 2 Centers in Beijing, China Using the Gastroesophageal Reflux Disease Questionnaire.

BACKGROUND This retrospective study from 2 centers in Beijing, China aimed to assess the safety and efficacy of endoscopic radiofrequency therapy under direct vision in 59 patients with gastroesophageal reflux disease (GERD) using the gastroesophageal reflux disease questionnaire (GerdQ). MATERIAL AND METHODS Fifty-nine GERD patients who underwent endoscopic radiofrequency treatment were included. Patients were divided into 2 groups: the endoscopic radiofrequency therapy under direct vision group and the non-direct vision radiofrequency therapy group. Indicators such as GerdQ score, lower esophageal sphincter (LES) pressure, DeMeester score, acid exposure time, and proton pump inhibitors (PPIs) use were collected before and after radiofrequency treatment. Postoperative complications were also recorded. The efficacy and safety of endoscopic radiofrequency therapy under direct vision were evaluated by comparing the indicators of patients in the 2 groups. RESULTS At 3 months after radiofrequency treatment, patients in the endoscopic radiofrequency therapy under direct vision group improved significantly in GerdQ score, decreased from 11.0 (10.0, 12.0) to 6.0 (6.0, 8.0), better than patients in the non-direct vision radiofrequency therapy group, and the better improvements remained at 12 months after the procedure (P<0.05). At 6 months after treatment, patients in the endoscopic radiofrequency therapy under direct vision group had significant improvements in LES pressure, which increased from 8.15 (3.18, 12.88) mmHg to 15.20 (10.25, 27.03) mmHg (P<0.05). There were no severe complications in our trial. CONCLUSIONS When compared with non-visualized endoscopic radiofrequency therapy, treatment under direct vision was safer and improved the GerdQ score and LES pressure at up to 12 months.

Ketamine Induces Ferroptosis of Liver Cancer Cells by Targeting lncRNA PVT1/miR-214-3p/GPX4.

BACKGROUND: Liver cancer ranks the top four malignant cancer type worldwide, which needs effective and safe treatment. Ferroptosis is a novel form of regulated cell death driven by iron-dependent lipid peroxidation and has been regarded as a promising therapeutic target for cancers. In this work, we aimed to study the effects of anesthetic ketamine on proliferation and ferroptosis of liver cancer. METHODS: Cell viability and proliferation were detected by cell counting kit 8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assay. Ferroptosis was determined by levels of Fe2+, lipid reactive oxygen species (ROS), and malondialdehyde (MDA). RNA levels of lncPVT1, miR-214-3p, and glutathione peroxidase 4 (GPX4) were checked by real-time PCR assay. Clinical liver tumor samples were collected to detect the levels of long noncoding RNA lncPVT1, miR-214-3p, and GPX4, and their correlation was evaluated by Pearson comparison test. Luciferase reporter gene assay and RNA pulldown were conducted to determine the binding between lncPVT1, miR-214-3p, and GPX4 3'UTR. RESULTS: Ketamine significantly suppressed viability and proliferation of liver cancer cells both in vitro and in vivo, as well as stimulated ferroptosis, along with decreased expression of lncPVT1 and GPX4. LncPVT1 directly interacted with miR-214-3p to impede its role as a sponge of GPX4. Depletion of lncPVT1 accelerated the ferroptosis of live cancer cells, whereas miR-214-3p inhibition and GPX4 overexpression reversed this effect. Ketamine-induced cell growth suppression and ferroptosis were also suppressed by miR-214-3p inhibition and GPX4 overexpression. CONCLUSION: In this work, we determined that ketamine suppressed viability of liver cancer cells and induced ferroptosis and identified the possible regulatory mechanism of lncPVT1/miR-214-3p/GPX4 axis.

Design, synthesis and biological evaluation of novel plumbagin derivatives as potent antitumor agents with STAT3 inhibition.

Based on the structure of signal transducer and activator of transcription 3 (STAT3), a series of 1,4-naphthoquinones derived from plumbagin (PL) with STAT3 inhibition potential were designed, synthesized, and biologically evaluated in vitro against several human cancer cell lines (MDA-MB-231, HepG2 and A549 cells) and three normal cells. The structure-activity relationship (SAR) and molecular docking result showed that the presence of hydroxyl group at C-5 of PL might interact with STAT3 in the form of hydrogen bonds, which is conducive to the binding of this kind structures with STAT3. Among the target compounds, 7a displayed the most potent inhibition against cancer cells and weaker cytotoxicity on normal cells than PL. The western bolting analysis showed that 7a could suppress the phosphorylation of STAT3 as well as the downstream genes instead of affecting its upstream tyrosine kinases (Src and JAK2) levels and p-STAT1 expression. Furthermore, molecular docking indicated that 7a bound to STAT3 more tightly than PL, and it could significantly induce the apoptosis of cancer cells in vitro. All these results may provide reference for the discovery of effective STAT3 inhibitors.

Synthesis of Ordered Mesoporous ZnO Nanostructures for Gas Sensing.

In this study, the ordered mesoporous jar structure ZnO particles have been synthesized by template method. The cetyltrimethylammonium bromide (CTMAB) was used as the template agent, and zinc acetate dihydrate was used as zinc sources. The prepared material has ordered mesoporous on the surface. The prepared ordered mesoporous ZnO particles showed the hexagonal prisms hollow jar structure, the hexagonal prisms average diameter was about 150 nm, the average length was about 200 nm, and the jar average diameter was about 100 nm. The prepared materials were used as a gas sensor to test the toxic gas. The ordered mesoporous ZnO material showed more excellent gas sensing performances than the imporous ZnO material which was prepared without template agent by the same method. In particular, the ordered mesoporous ZnO showed a higher response to NOx, the detection limit reached to 0.5 ppm, the sensitivity reached to 66.92, and the response time was 1.08 s to 100 ppm NOx at 193 °C. The prepared material will be an excellent gas sensing matrix materials, and have a wide application prospect in gas sensors field.

Clinical features and prognosis of microscopic polyangiitis with usual interstitial pneumonia compared with idiopathic pulmonary fibrosis.

INTRODUCTION: Pulmonary involvement in microscopic polyangiitis (MPA) is common, little is known about the clinical features of MPA with interstitial pneumonia (MPA-IP). OBJECTIVES: This study aimed to explore the prevalence of microscopic polyangiitis associated usual interstitial pneumonia (UIP)(MPA-UIP) and compare its clinical features and prognosis with those of MPA-non-UIP and idiopathic pulmonary fibrosis (IPF). METHODS: A total of 73 patients with MPA-IP were identified and divided into MPA-UIP patients and MPA-non-UIP patients. The clinical characteristics and survival of MPA-UIP patients were analysed and compared with those of MPA-non-UIP patients and 68 patients with IPF. RESULTS: The results showed that 34/73 (47%) MPA-IP patients were classified as MPA-UIP patients. Compared with MPA-non-UIP patients, MPA-UIP patients tend to have longer duration of symptoms prior to diagnosis and usually have pulmonary involvement as the initial presentation. However, they were less likely to have proteinuria and/or hematuria. Compared with IPF patients, MPA-UIP patients usually had multisystem damage, positive anti-neutrophil cytoplasmic autoantibodies and elevated levels of nonspecific inflammatory markers. MPA-UIP death was concentrated mainly in the first 3 months after diagnosis and resulted in a higher early mortality compared with IPF. CONCLUSION: UIP is the most frequent type of MPA-IP. These patients tend to have longer duration of symptoms prior to diagnosis and usually have pulmonary involvement as the first presentation. However, they are less likely to have proteinuria and/or hematuria. MPA patients with UIP can be differentiated from IPF patients through comprehensive analysis of clinical and laboratory findings.

Discovery of novel NO-releasing celastrol derivatives with Hsp90 inhibition and cytotoxic activities.

To develop multifunctional drugs, a series of celastrol/NO donor hybrids were designed, synthesized and evaluated. The detection of NO release amounts showed that the more NO of these hybrids released, the more tumor cells were inhibited. 11b, which released the highest level of NO in vitro, exhibited superior potency (IC50 = 0.48 ±â€¯0.06 µM) compared to the other compounds. Further pharmacological studies showed that 11b induced dysregulations of the Hsp90 clients (Akt and Cdk4), apoptosis, and cell cycle arrested at G0/G1 phase against A549 cells. These results suggested that inhibition of Hsp90 and release of NO was synergistic in cancer cells. Overall, the NO-releasing capacity and the inhibition of Hsp90 pathway signaling might explain the potent anti-proliferative activities of these compounds.

Effects of propofol/remifentanil-based total intravenous anesthesia versus sevoflurane-based inhalational anesthesia on the release of VEGF-C and TGF-ß and prognosis after breast cancer surgery: a prospective, randomized and controlled study.

BACKGROUND: Vascular endothelial growth factor (VEGF) and transforming growth factor-ß (TGF-ß) have been involved in tumor growth and metastasis. Sevoflurane may promote angiogenesis, whereas propofol can present an anti-angiogenic effect. In this study, we compared the effects of propofol/remifentanil-based total intravenous anesthesia (TIVA) and sevoflurane-based inhalational anesthesia on the release of VEGF-C and TGF-ß, as well as recurrence- free survival (RFS) rates in the patients undergoing breast cancer surgery. METHODS: Eighty female patients undergoing breast cancer resection were enrolled and randomized to receive either sevoflurane-based inhalational anesthesia (SEV group) or propofol/remifentanil-based TIVA (TIVA group). The serum concentrations of VEGF-C and TGF-ß before and 24 h after surgery were measured and RFS rates over a two-year follow-up were analyzed in both groups. The postoperative pain scores assessed using a visual analogue scale (VAS) and the use of perioperative opioids were also evaluated. RESULTS: Although VAS scores at 2 h and 24 h after surgery were comparable between the two groups, there were more patients receiving postoperative fentanyl in the TIVA group (16[40%]) compared with the SEV group (6[15%], p = 0.023). VEGF-C serum concentrations increased after surgery from 105 (87-193) pg/ml to174 (111-281) pg/ml in the SEV group (P = 0.009), but remained almost unchanged in the TIVA group with 134 (80-205) pg/ml vs.140(92-250) pg/ml(P = 0.402). The preoperative to postoperative change for VEGF-C of the SEV group (50 pg/ml) was significantly higher than that of the TIVA group (12 pg/ml) with a difference of 46 (- 11-113) pg/ml (P = 0.008). There were also no significant differences in the preoperative and postoperative TGF-ß concentrations between the two groups. The two-year RFS rates were 78% and 95% in the SEV and TIVA groups (P = 0.221), respectively. CONCLUSION: In comparison with sevoflurane-based inhalational anesthesia, propofol/remifentanil -based total intravenous anesthesia can effectively inhibit the release of VEGF-C induced by breast surgery, but didn't seem to be beneficial in the short-term recurrence rate of breast cancer. TRIAL REGISTRATION: Chictr.org.cn ChiCTR1800017910 . Retrospectively Registered (Date of registration: August 20, 2018).

Down-expression of GOLM1 enhances the chemo-sensitivity of cervical cancer to methotrexate through modulation of the MMP13/EMT axis.

The highly refractory nature of cervical cancer to chemotherapeutic drugs and its epithelial-to-mesenchymal transition (EMT) are the key reasons contributing to the poor prognosis of this disease. Golgi Membrane Protein 1 (GOLM1), a protein involved in the trafficking of proteins through the Golgi apparatus, has been shown to be oncogenic in a variety of human cancers. Herein, we found GOLM1 was markedly up-regulated in cervical cancer and GOLM1 down-expression enhanced the anti-tumor effect of methotrexate. By performing mechanistic studies using both in vitro and in vivo models, we found that GOLM1 could target matrix metallopeptidase 13 (MMP13), a member of the MMPs, and regulate the EMT process. Moreover, altered EMT progression compromised the chemotherapy-enhancing effects of GOLM1 knock-down. Finally, we found significantly higher levels of GOLM1 and MMP13 in cervical cancer tissues compared with adjacent noncancerous tissues, and this was also associated with poor cervical cancer patients' prognosis. Taken together, our results suggest that the GOLM1/MMP13/EMT axis is an important factor involved in regulating methotrexate in cervical cancer, and highlights the potential of novel GOLM1-based clinical modalities as a therapeutic approach in cervical cancer patients.

Novel anticancer hybrids from diazen-1-ium-1,2-diolate nitric oxide donor and ROS inducer plumbagin: Design, synthesis and biological evaluations.

High levels of both nitric oxide (NO) and reactive oxygen species (ROS) could act as pro-apoptotic signals in cancerous cells. In this study, we conjugated diazeniumdiolates (NONOates), an important class of NO donors, with a natural occurring plumbagin (PL) which is primarily an excellent ROS inducer. Herein, a total of 12 novel plumbagin/NONOate hybrids have been synthesized and evaluated for their inhibitory effects on a panel of human cancer cell lines (MDA-MB-231, A549, HepG2 and HCT-116 cells) and two normal human cells (HK-2 and WRL-68 cells). Among them, compounds 10a and 10b demonstrated superior potencies compared to their parent compound (IC50 values of 3.48-6.68 µM) against the above cancer cell lines but weak inhibitory effects on normal cells. In concordance with their selective cytotoxicities, 10a and 10b released higher level of NO in cancer cells than normal cells. Besides, the potent compound 10a induced apoptosis of A549 cells in a concentration-dependent manner and resulted in more ROS generation compared with the parent compound plumbagin.

Study on room temperature gas-sensing performance of CuO film-decorated ordered porous ZnO composite by In2O3 sensitization.

For the first time, ordered mesoporous ZnO nanoparticles have been synthesized by a template method. The electroplating after chemical plating method was creatively used to form copper film on the surface of the prepared ZnO, and then a CuO film-decorated ordered porous ZnO composite (CuO/ZnO) was obtained by a high-temperature oxidation method. In2O3 was loaded into the prepared CuO film-ZnO by an ultrasonic-assisted method to sensitize the room temperature gas-sensing performance of the prepared CuO/ZnO materials. The doped In2O3 could effectively improve the gas-sensing properties of the prepared materials to nitrogen oxides (NO x ) at room temperature. The 1% In2O3 doped CuO/ZnO sample (1 wt% In2O3-CuO/ZnO) showed the best gas-sensing properties whose response to 100 ppm NO x reached 82%, and the detectable minimum concentration reached 1 ppm at room temperature. The prepared materials had a good selectivity, better response, very low detection limit, and high sensitivity to NO x gas at room temperature, which would have a great development space in the gas sensor field and a great research value.

[Data Mining-revealed Characteristics of Clinical Application of Scalp Acupuncture].

OBJECTIVE: To explore the regularity and characteristics of clinical application of scalp acupuncture therapy for different types of clinical conditions so as to provide a reference for clinical practice. METHODS: In the present study, "head acupuncture" and"scalp acupuncture" were used as the keywords to search papers and academic dissertations having definite standards for diagnosis and therapeutic effect assessment and published in journals and academic conferences collected in database China National Knowledge Internet(CNKI) from January 1 of 1959 to December 31 of 2016, followed by constructing a database after sorting, screening, recording, extracting, and statistical analysis by using a computer. Then, the data mining was conducted for summarizing the indications of disease categories, involved medical departments, needle-insertion methods, needle manipulation techniques, academic schools, and clinical efficacy of scalp acupuncture therapy. RESULTS: As a result, a total of 587 papers met our including criteria were analyzed. The scalp acupuncture therapy was widely employed in the treatment of various clinical conditions of different departments, with the application frequency being the internal medicine (438 times), surgery (75 times), pediatrics (44 times), etc. Of the indicated 102 types of clinical problems, 55 belong to the internal medicine, constituting of 53.92%, particularly the cerebral apoplexy and its sequelae with the top application frequency being 102 and 115 times, respectively. In terms of needle inserting methods mentioned in partial papers (most papers do not mention), fingernail-pressing-aided needle insertion, needle-twirling insertion, fingers-squeezed-needle insertion, particularly the swiftly rotating needle insertion and rapid needle-propelling insertion were most commonly used.Regarding the needle manipulation method, rapid needle twirling technique was frequently employed, usually at a frequency of approximately 200 times per min. In regard to the academic schools, JIAO Shun-fa's scalp acupuncture system was most frequently used, followed by the international standardized scalp acupuncture. The therapeutic effect of scalp acupuncture is effective in the treatment of different conditions of various departments, especially those of the dermatology and gynecology. CONCLUSION: Scalp acupuncture has superiority in the treatment disorders of the internal medicine and has been demonstrated to have positive effects for many types of problems, particularly for apoplexy and its sequelae. Rapid needle-propelling insertion and rapid needle-twirling technique are often employed.

Evaluation of Radioiodinated 1,4-Naphthoquinones as Necrosis Avid Agents for Rapid Myocardium Necrosis Imaging.

PURPOSE: Identifying necrotic myocardium in ischemic regions is of great importance for risk stratification and clinical decision-making. However, rapid noninvasive imaging of necrotic myocardium is still challenging. This study sought to evaluate the potential of 1,4-naphthoquinones to rapidly visualize necrotic myocardium and the possible mechanisms of necrosis avidity. PROCEDURES: Six 1,4-naphthoquinones were radiolabeled with iodine-131 and the necrosis avidity was estimated in mouse models with muscular necrosis by gamma counting and autoradiography. The necrotic myocardium imaging property and biodistribution of [131I]naphthazarin (6) were determined in rat models with re-perfused myocardial infarction. A possible mechanism of necrosis avidity was explored by in vitro DNA-binding and in vivo blocking experiments. RESULTS: The radiochemical purities of the six radiotracers were greater than 95 %. The uptakes in necrotic muscles of all six radiotracers were higher than those in viable muscles, and [131I]naphthazarin (6) showed the highest necrotic-to-viable ratio and necrosis-to-blood ratio at all tested time points. The necrotic myocardium could be clearly visualized by single-photon emission computed tomography/x-ray computed tomography (SPECT/CT) using [131I]naphthazarin (6) as early as 3 h post-injection. Post-mortem biodistribution showed the uptake of [131I]naphthazarin (6) in necrotic myocardium was 11.67-fold higher than that in viable myocardium. Absorption spectra and emission spectra suggested naphthazarin (6) could bind to DNA through intercalation. The uptake of [131I]naphthazarin (6) in necrotic muscle could be significantly blocked by excessive ethidium bromide (a typical DNA intercalator) and cold naphthazarin (6) with 63.49 and 71.96 % decline at 3 h post-injection in vivo, respectively. CONCLUSIONS: 1,4-Naphthoquinones retained necrosis avidity and [131I]naphthazarin (6) rapidly visualized necrotic myocardium. The necrosis avidity mechanism of [131I]naphthazarin (6) may be attributed to its binding with exposed DNA in necrotic tissues.

Design, synthesis, and cytotoxic evaluation of novel scopoletin derivatives.

A series of scopoletin derivatives were designed and synthesized by introducing α-aminoacetamide, acrylamide and ß-aminopropamide, respectively, to 3-position of scopoletin, and their chemical structures were confirmed by ESI-MS, IR, 1 H NMR, and 13 C NMR spectra. All target compounds were evaluated in vitro against four human cancer cell lines (MDA-MB-231, MCF-7, HepG2, and A549) by MTT method. Cytotoxic assay showed that compounds 7a, 7b, 7e, 7f, 8a, and 8e exhibited more potent cytotoxicities compared to scopoletin. Besides, we have further evaluated the growth inhibitory activities of these selected compounds against normal tissue cell lines HFL-1. Although compound 8a showed the strongest antiproliferative activity in vitro, it exhibited strong cytotoxicity on normal cells HFL-1, which limited its further study. Compound 7a and 7b exhibited higher antiproliferative activity against MDA-MB-231 and HepG2 cells and weak cytotoxicity on HFL-1, which suggested that 7a and 7b might be ideal anticancer candidates. The SARs showed that the introduction of the acrylamide and its analogues ß-aminopropamide could significantly improve activity, while the α-aminoacetamide failed to enhance potency obviously. Therefore, the mechanism of compound 7a and 7b is worthy of further research and the structure of compound 8a should be further optimized.

[Rule of Clinical Application of Auricular Acupuncture Based on Data Mining].

OBJECTIVE: To explore the rule of clinical application of auricular acupuncture therapy by data mining in order to guide clinical practice. METHODS: The data base about single auricular acupuncture therapy for different clinical diseases was established by collection, sorting, screening, recording, collation, data extraction, statistic analysis on data samples from journals, academic theses dissertations published in near 60 years. The application rules of auricular therapy including its predominant diseases, stimulus modality, therapeutic effect, and angle of needling were summarized by data mining technique. RESULTS: Auricular acupuncture therapy has been widely and mostly used in the internal medicine department, accounting for 48.56%. Of stimulus modalities, auricular point paste and pressure is applied with the highest frequency, accounting for 64%. The highest effective rate is found in the surgery department diseases(81.41%). Pressure is the most effective stimulus in the internal medi-cine department, and bloodletting combined with paste and pressure in the surgery department, auricular point injection in the gynecology and pediatrics departments, bloodletting in the ophthalmology and otorhinolaryngology department, and auricular point incision in the dermatology department. Auricular point injection has remarkable effect. Bloodletting combined with paste and pressure has nearly the same effect as bloodletting in the same medical department except dematology department. Otherwise, angle of needling is rarely studied. CONCLUSIONS: Auricular therapy is widely used and has remarkable effect in treating diseases by using different stimulus modalities. Whereas the angle of needling is rarely studied and future investigation is needed.

[Research of Characteristics of Stimulation Methods and Application of Acupoint in Auricular Needle Therapy Based on Data Mining].

In the present paper, using data mining technology,the authors downloaded information from databases on auricular needle therapy, and obtained data samples from journals and academic dissertations involving the application of auricular needle therapy to treat diseases, and then screened, audited, and extracted the data and performed a statistical analysis. The authors extracted data on the application of auricular needle therapy in the stimulation methods of medicine (needling instrument), selection of the side of ear to treat disease and the number of times the ear was pressed per day and the compression time. In the stimulation methods, the needling instrument varied, the seeds of cowherb Semen Vaccariae were applied in 60.89% of the total stimulation methods. The number of times the ear was pressed per day and the compression time in the clinic were optional. The main points in auricular needle therapy were the contralateral side; there was no significant difference in the effect of a single side or both sides of the ear to treat disease.

Novel NO-releasing plumbagin derivatives: Design, synthesis and evaluation of antiproliferative activity.

A series of plumbagin/NO donor hybrids were designed, synthesized and evaluated in vitro against triple negative breast cancer (MDA-MB-231), hepatocellular (HepG2) and lung (A549) carcinoma cells. Most furoxan-based plumbagin derivatives exhibited significantly superior potency compared to their parent compound. Noticeably, MDA-MB-231 cells are the most sensitive to these furoxan-based plumbagin derivatives as evidenced by IC50 values ranging from 1.24 to 5.20 µM. Besides, NO released amounts detection of all hybrids suggested that in most cases, the antiproliferative activities were positively correlated with the levels of intracellular NO release in MDA-MB-231 cells. The most active compound (11a) also possessed higher chemical stability at different pHs (6.0, 7.4 and 8.0) than plumbagin. Together, the above promising results warrant the future potential of plumbagin/NO hybrids as the lead compounds against triple negative breast cancer deserving further research.

Design, synthesis and cytotoxic evaluation of nitric oxide-releasing derivatives of isosteviol.

Twenty-six novel isosteviol derivatives coupled with two types of nitric oxide (NO) donors (furoxans and NONOates) were synthesized and screened for cytotoxic activities against four human cancer cell lines with sunitinib as the positive control. The results showed that seven furoxan-based derivatives (8a, 8b, 8c, 8d, 8e, 9e, and 9f) exhibited desirable cytotoxic activities, while NONOate-based derivatives displayed poor potency because of unstability. Compared with sunitinib, compounds 8a and 8e were more active on all tested cell lines, especially in HCT116 (8a, IC50  = 0.48 ± 0.02 µm; 8e, IC50  = 0.94 ± 0.01 µm); compounds 8b and 8d were more potent on HCT116 (IC50  = 3.39 ± 0.06 and 3.29 ± 0.03 µm), HepG2 (IC50  = 1.05 ± 0.03 and 5.37 ± 0.08 µm), and SW620 (IC50  = 1.33 ± 0.02 and 4.11 ± 0.05 µm) cell lines, and 8c exhibited higher activities on HepG2 cells with an IC50  = 4.76 ± 0.14 µm. NO-releasing experiment of compounds 8a-e, 17a, 18a, 19a, and 21a reminded us that NO-releasing amount of this series of isosteviol derivatives positively correlates with their cytotoxic activities.