Fulvanines J-K, two rare lactam pyrrole alkaloids from Hemerocallis fulva.

Two rare jatropham lactam derivatives, named as fulvanines J-K (1-2), together with six known pyrrole alkaloids, 5,5'-oxydi(3-methyl-3-pyrrolin-2-one) (3), (-)-5-hydroxy-3-methyl-3-pyrrolin-2-one (jatropham) (4), (±)-5-O-methyljatropham (5), perlolyrine (6), butyl-2-formyl-5-(hydroxymethyl)-1H-pyrrole-1-butanoate (7), and hemerocallisamine II (8), were isolated from the flower of Hemerocallis fulva. Their structures were elucidated on the basis of spectroscopic methods and compared with the NMR spectra data in the literature. All compounds were evaluated for their anti-complementary activity in vitro, and compounds 1, 4, and 6 exhibited anti-complement effect with CH50 values from 0.61 to 1.42 mM.

Distinct Responses of Thitarodes xiaojinensis ß-1,3-Glucan Recognition Protein-1 and Immulectin-8 to Ophiocordyceps sinensis and Cordyceps militaris Infection.

Melanization and encapsulation are prominent defense responses against microbes detected by pattern recognition receptors of their host insects. In the ghost moth Thitarodes xiaojinensis, an activated immune system can melanize and encapsulate the fungus Cordyceps militaris However, these responses were hardly detected in the host hemolymph postinfection of another fungus Ophiocordyceps sinensis The immune interaction between O. sinensis and the host remains largely unknown, which hinders the artificial cultivation of Chinese cordyceps. We found that T. xiaojinensis ß-1,3-glucan recognition protein-1 (ßGRP1) was needed for prophenoloxidase activation induced by C. militaris Failure of ßGRP1 to recognize O. sinensis is a primary reason for the lack of melanization in the infected host. Lyticase or snailase treatment combined with binding and immunofluorescence detection showed the existence of a protective layer preventing the fungus from ßGRP1 recognition. Coimmunoprecipitation and mass spectrometry analysis indicated that ßGRP1 interacted with immulectin-8 (IML8) via binding to C. militaris IML8 promotes encapsulation. This study suggests the roles of T. xiaojinensis ßGRP1 and IML8 in modulating immune responses against C. militaris Most importantly, the data indicate that O. sinensis may evade melanization by preventing ßGRP1 recognition.

[Systematic review and Meta-analysis of efficacy and safety of Fengliao Changweikang prescription in treatment of acute gastroenteritis].

This study systematically evaluated the clinical efficacy and safety of Fengliao Changweikang prescription for treating acute gastroenteritis(AGE). The databases of CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library and two clinical trial registration platforms were retrieved from inception to August 30, 2022, to collect randomized controlled trial(RCT) on Fengliao Changweikang prescription treating AGE. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment according to pre-established inclusion and exclusion criteria. RevMan 5.4.1 was used for data analysis. Finally, 18 RCTs were included, involving 3 489 patients. Meta-analysis showed that compared with conventional western medicine, Fengliao Changweikang prescription improved the relief rate of abdominal pain(RR=1.27, 95%CI[1.17, 1.38],P<0.000 01); Fengliao Changweikang prescription + conventional western medicine increased the cure rate(RR=1.43, 95%CI[1.12, 1.82], P=0.004), shortened the duration of diarrhoea(RR=-1.65, 95%CI[-2.44,-0.86], P<0.000 1), abdominal pain(RR=-1.46, 95%CI[-2.00,-0.92], P<0.000 01), vomiting(RR=-2.16, 95%CI[-2.51,-1.81], P<0.000 01) and fever(RR=-2.61, 95%CI[-4.00,-1.23], P=0.000 2), down-regulated the level of interleukin-8(IL-8)(RR=-1.07, 95%CI[-1.26,-0.88], P<0.000 01), IL-6(RR=-8.24, 95%CI[-8.99,-7.49], P<0.000 01) and hypersensitive C-reactive protein(hs-CRP)(RR=-3.04, 95%CI[-3.40,-2.69], P<0.000 01) and recurrence of AGE(RR=0.20, 95%CI[0.05, 0.90], P<0.04). In conclusion, Fengliao Changweikang prescription was safe in clinical application. It was beneficial to alleviate the clinical symptoms of diarrhea, abdominal pain, vomiting, and fever, and down-regulate the levels of some serum inflammatory factors in AGE patients. However, considering that few high-quality studies have evaluated the efficacy and safety of Fengliao Changweikang prescription in treatment of AGE, further evidence is needed in the future.

[Systematic review and Meta-analysis of Biling Weitong Granules in treatment of stomach ache disorder].

This study aimed to evaluate the efficacy and safety of Biling Weitong Granules in the treatment of stomach ache disorder. Randomized controlled trial(RCT) of Biling Weitong Granules in the treatment of digestive diseases with stomach ache disorder as the primary symptom was retrieved from Chinese and English electronic databases and trial registration platforms from database inception to June 10, 2022. Two investigators conducted literature screening and data extraction according to the screening criteria. The Cochrane risk-of-bias tool(v 2.0) was used to assess the risk of bias in the included studies. Analyses were performed using RevMan 5.4 and R 4.2.2, with summary estimates measured using fixed or random effects models. The primary outcome indicators were the visual analogue scale(VAS) scores and stomach ache disorder symptom scores. The secondary outcome indicators were clinical recovery rate, Helicobacter pylori(Hp) eradication rate, and adverse reaction/events. Twenty-seven RCTs were included with a sample size of 2 902 cases. Meta-analysis showed that compared with conventional western medicine treatments or placebo, Biling Weitong Granules could improve VAS scores(SMD=-1.90, 95%CI[-2.18,-1.61], P<0.000 01), stomach ache disorder symptom scores(SMD=-1.26, 95%CI[-1.71,-0.82], P<0.000 01), the clinical recovery rate(RR=1.85, 95%CI[1.66, 2.08], P<0.000 01), and Hp eradication rate(RR=1.28, 95%CI[1.20, 1.37], P<0.000 01). Safety evaluation revealed that the main adverse events in the Biling Weitong Granules included nausea and vomiting, rash, diarrhea, loss of appetite, and bitter mouth, and no serious adverse events were reported. Egger's test showed no statistical significance, indicating no publication bias. The results showed that Biling Weitong Granules in the treatment of digestive system diseases with stomach ache disorder as the primary symptom could improve the VAS scores and stomach ache disorder symptom scores of patients, relieve stomach ache disorder, and improve the clinical recovery rate and Hp eradication rate, with good safety and no serious adverse reactions. However, the quality of the original studies was low with certain limitations. Future studies should use unified and standardized detection methods and evaluation criteria of outcome indicators, pay attention to the rigor of study design and implementation, and highlight the clinical safety of the medicine to provide more reliable clinical evidence support for clinical application.

Taming Chiral Quaternary Stereocenters via Remote H-Bonding Stereoinduction in Palladium-Catalyzed (3+2) Cycloadditions.

Ring-opening transformations of donor-acceptor (D-A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium-catalyzed highly diastereo- and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron-withdrawing groups, a subset of D-A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five-membered heterocycles were produced in good yields and with high stereoselectivity (up to 99 % yields, 99 : 1 er and >19 : 1 dr). In-depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H-bonding in stereocontrol.

Anti-inflammatory Dimeric Benzophenones from an Endophytic Pleosporales Species.

Eight new polyketides, including three dimeric benzophenones, named dipleosporones A-C (1-3), three benzophenones (4-6), one xanthone (7), and one phenylbenzoate (8), along with seven known polyketides (9-15) were isolated from the fungus Pleosporales sp. YY-4. The structures of the new compounds were established on the basis of spectroscopic methods, including high-resolution electrospray ionization mass spectrometry and one- and two-dimensional nuclear magnetic resonance. This is the first report of a benzophenone dimer connection via a C bridge from natural sources. An anti-inflammatory assay indicated that the dimeric benzophenones (1-3) inhibited lipopolysaccharide-induced NO production in RAW 264.7 cells, with half-maximal inhibitory concentration (IC50) values ranging from 8.8 to 18.1 µM, being more potent than the positive control, dexamethasone (IC50 = 22.2 µM).

Euphatexols C - G, five new triterpenoids from the latex of Euphorbia resinifera.

Five new triterpenoids named as euphatexols C - G (1-5) were isolated from the latex of Euphorbia resinifera. Their chemical structures were determined by extensive spectroscopic analysis, including IR, HRMS, 1 D and 2 D NMR data. Compounds 1-5 showed moderate anti-inflammatory activity with IC50 values of 22.30, 48.04, 21.89, 38.15 and 41.15 µM, respectively.

[Scoping review of domestic and overseas hospital-based health technology assessment].

This paper systematically sorted out the related research on hospital-based health technology assessment(HB-HTA) and clarified the research status of this field to provide a basis for the future research direction and focus of HTA in traditional Chinese medicine(TCM) hospitals. Based on the scoping review, relevant research papers were retrieved from Chinese databases(including CNKI, Wanfang, VIP, and SinoMed) and PubMed and analyzed. Among the included 99 papers, the earliest one was published in 2005 in China, and the number of papers has been increasing since 2016. In terms of journals, the included papers were published in 39 journals, including 24 core ones and 2 SCI ones. In terms of the number of publications, the Chinese Journal of Evidence-Based Medicine accounted for the majority(n=6). Among the 175 authors involved, three of them published 15 papers, respectively, accounting for 20.83% and ranking the top, and they came from Renmin University of China and the National Health Commission of China. There were 38 first units dominated by hospitals. Hebei General Hospital published the most papers(n=10), followed by Renmin University of China(n=9) and the National Health Commission of China(n=7). In terms of research type, the research papers were dominated by evaluation and practice ones(n=29), followed by reviews(n=20). In terms of research topic, the research was mainly carried out from devices(n=26) and macro-perspective scope(n=24). Half of the research in China was funded. For 27 research papers published abroad, the number of publications in the past five years was small, with 16 countries involved. Developed countries paid more attention to this field than developing countries. Especially in Europe and the US, the publishing institutions were mainly universities, and the types of research were mainly interviews and evaluation or practice. In recent years, the attention of HB-HTA in China has been increasing year by year, and the development of related projects has provided a scientific decision-making basis for the admission and management of new technologies in hospitals in China. However, there are few researchers and institutions in this field, and the research scope is small. In the future, more investment is needed to encourage more hospitals, especially TCM hospitals, to carry out HB-HTA, explore the HB-HTA system suitable for Chinese conditions, and improve the scientific decision-making of hospitals.

[Four Chinese patent medicines for regulating stomach for functional dyspepsia: a rapid health technology assessment].

This study evaluated and compared the efficacy, safety and economy of four Chinese patent medicines(CPMs) in the treatment of functional dyspepsia(FD) using the method of rapid health technology assessment. It aims to provide decision-makers with rapid decision-making information. The eight Chinese and English databases were comprehensively and systematically searched for the relevant clinical research. Studies were screened and evaluated. A total of 110 studies were identified, including 95 randomized controlled trials(RCTs), 7 controlled clinical trials(CCTs), 7 systematic review/Meta-analysis and 1 economic evaluation, among which 28 were Dalitong Granules, 49 were Zhizhu Kuanzhong Capsules, 3 were Biling Weitong Granules and 30 were Qizhi Weitong Granules(Tablets/Capsules). The quality of the included literature was generally low. The efficacy of four CPMs alone or combined with western medicine in the treatment of FD is different. Dalitong Granules was used to treat motility disorder in FD. Zhizhu Kuanzhong Capsules and Qizhi Weitong Granules(Tablets/Capsules) can treat FD patients with anxiety and depression. Qizhi Weitong Granules(Tablets/Capsules) were mainly used in FD for perimenopausal patients. There were no serious adverse reactions in the clinical study of four CPMs in the treatment of FD. Dalitong Granules has better effects than mosapride in the treatment of FD, but the cost is slightly higher. The cost-effectiveness ratio of Zhizhu Kuanzhong Capsules in the treatment of FD patients with anxiety and depression was lower than that of Domperidone. In terms of average daily price, Qizhi Weitong Tablets has the highest price(27.00 yuan per day), Qizhi Weitong Granules has the lowest price(5.04 yuan per day), Biling Weitong Granules has a relatively high price(15.53 yuan per day), followed by Dalitong Granules(13.03 yuan per day). The evidence of Dalitong Granules covered the efficacy, safety and economy, which is relatively complete compared with the other three drugs. It has effective potential in the treatment of motility disorder in FD. Further research in this field in the future is needed.

[Scoping review of clinical evidence of Chinese patent medicines for digestive system diseases in children].

This study analyzed and reported the basic information and clinical evidence of Chinese patent medicines for digestive system diseases in children in a scoping review manner. Based on the drug instructions, the basic information of Chinese patent medicines for digestive system diseases in children was obtained by searching the three lists of national medicines. At the same time, the relevant clinical literatures from the first day of establishment to March 7, 2022 were obtained from Chinese and English databases. According to the screening criteria, 39 Chinese patent medicines were included, involving 8 dosage forms. Eight Chinese medicines including Crataegi Fructus, Poria, Citri Reticulatae Pericarpium, Hordei Fructus Germinatus, Arecae Semen, Massa Medicata Fermentata, Dioscoreae Rhizoma, and Atractylodis Macrocephalae Rhizoma were frequently used, and the main effects were invigorating spleen, checking diarrhea, promoting digestion, clearing heat, and harmonizing stomach. The indications for Chinese patent medicines were mainly diarrhea, anorexia, food accumulation, dyspepsia, and rotavirus enteritis in children. Among all drug instructions, only 4 mentioned adverse reactions and 6 mentioned contraindications. Ninety-two clinical studies were included ultimately, including 84 randomized controlled studies, 2 systematic reviews/Meta-analysis, 1 retrospective study, and 5 case series. The literatures only covered 21 kinds of Chinese patent medicines, with the most studies related to Xingpi Yanger Granules, accounting for 32.6% of the total literature volume. The sample size in the literatures was mainly focused on 51-200 cases, and 51-100 cases were selected by the most literatures, accounting for 34.45%. The interventions of the experimental group were mainly Chinese patent medicines or Chinese patent medicines combined with western medicines. The literatures with treatment course of 0-7 d accounted for the largest proportion(51.10%). The effective rate and symptom improvement time were used as the indexes to evaluate the results. The main adverse reactions were vomiting, constipation, nausea, rash, cold, diarrhea, redness of the skin around the umbilicus, or red itchy skin. The analysis of this study found that Chinese patent medicines have good curative effect and research prospects in the treatment of digestive system diseases in children. However, most clinical evidence has problems, such as limited indexes to evaluate the results, lack of traditional Chinese medicine characteristics, uneven quantity and low quality of Chinese patent medicine literatures, and insufficient specification of instructions. In the future, high-quality clinical studies on this field should be actively carried out, and economic studies and clinical comprehensive evaluation of Chinese patent medicines should be strengthened to explore the characteristics and advantages of its treatment, so as to provide decision-making basis for finding the accurate clinical positioning and promoting the rational clinical application of Chinese patent medicines for treating digestive system diseases in children.

[Scoping review of rapid health technology assessment].

This study aims to summarize the research on rapid health technology assessment(RHTA) based on scoping review, which is expected to serve as a reference for future research on RHTA. First, articles on RHTA were retrieved from both Chinese and English databases. After data screening and extraction by two personnel independently, descriptive analysis was conducted on the results, and evidence distribution was analyzed based on tables, bar charts, line charts, radar charts, and pie charts. Finally, a total of 82 eligible articles were included and the characteristics were as follows.(1) Articles on RHTA were mainly published from 2011 to 2022. The number of articles showed an obvious increase from 2014 and surged in 2019.(2) Among the journals with the above RHTA papers published, Chinese Journal of New Drugs(21.5%), Evaluation and Analysis of Drug-Use in Hospitals of China(16.9%), and Chinese Pharmacy(15.4%) topped the Chinese journals in the number of the papers, while International Journal of Technology Assessment in Health Care(23.5%), Reviews in Medical Virology(11.8%), and Value in Health(11.8%) came out on top in the English journals.(3)The RHTA of drugs(especially western medicine)(68.7%) dominated the eligible articles, followed by the RHTA of therapy technology(13.1%), detection technology(5.1%), and diagnosis technology(1.0%). There was a significant gap in the number of studies among different health technology categories and an imbalance in the types of health technologies involved in the overall RHTA studies.(4) RHTA of tumors has been the research focus in recent years. In summary, RHTA plays a positive role in rapid health decision-making, but there is a lack of primary data sources at present. Compared with the systematic review, Meta-analysis, and pharmacoeconomic studies, a few reports on health technology assessment(HTA) were included. In the future, research on the evaluation of the safety, efficacy, cost effectiveness and social applicability of health technologies should be further strengthened.

[Multi-criteria decision analysis in clinical comprehensive evaluation of Chinese patent medicine].

Multi-criteria decision analysis(MCDA), a comprehensive analysis method that can help decision-makers consider multiple criteria systematically, has been used for clinical comprehensive evaluation of drugs, such as chemicals and Chinese patent medicines. The present study summarized the theoretical basis of MCDA and its application in the clinical comprehensive evaluation of drugs and put forward suggestions. MCDA includes problem identification, structuring problem, model building, and using the model to inform and challenge thinking to develop an action plan. The modeling methods include value measurement models, outranking models, and reference-level models. The value measurement model is the most commonly used method in healthcare. The implementation steps of MCDA consist of defining the decision problem, selecting and structuring criteria, measuring performance, scoring alternatives, weighting criteria, calculating aggregate scores, dealing with uncertainty, and reporting and examination of findings. It is urgent to carry out the clinical comprehensive evaluation of Chinese patent medicine, the important part of traditional Chinese medicine(TCM), to promote its scientization, homogenization, and standardization. It is of great significance to carry out the clinical comprehensive evaluation of Chinese patent medicine with MCDA, which should be demand-oriented, coordinated by many parties, and learn from international experience and successful practice to establish the corresponding technical guidelines, specifications, and evaluation tools, so as to provide technical support for Chinese patent medicine supply and policy formulation.

[Enlightenment of WHO guideline on institutionalizing health technology assessment mechanism for traditional Chinese medicine].

To promote the institutionalization of the health technology assessment(HTA) mechanism in various countries, World Health Organization(WHO) has published the Institutionalizing Health Technology Assessment Mechanisms: a How to Guide to introduce five steps of institutionalizing the HTA mechanism systematically, specifically, "establishing a mandate; establishing the legal framework; reviewing or establishing the legal framework; establishing institutional and governance arrangements; processes and evidence required for assessment and appraisal; and monitoring and evaluation". Traditional Chinese medicine(TCM) HTA can provide scientific information and decision-making evidence for decision-makers at all levels to select TCM health technology reasonably, and promote the high-quality development of the TCM healthcare system. However, TCM HTA is in its infancy, and it is imperative to carry out relevant work under the guidance of global standard documents to ensure standardization, transparency, and fairness. In light of the WHO guidance, this research group put forward the necessity and logical framework for the institutionalizing HTA mechanism of TCM, which is helpful to establish the institutionalizing HTA mechanism in line with national conditions and suitable for TCM, provide scientific guidance for the research of TCM HTA, and contribute to TCM healthcare decision-making.

[Secondary metabolites of endophyte Hypoxylon sp. HD-2014 from Uncaria rhynchophylla].

This study aims to investigate the compounds in the product of rice fermented with endophyte Hypoxylon sp.HD-2014 from Uncaria rhynchophylla.To be specific, normal-phase, MCI, Sephadex LH-20, and semi-preparative high performance liquid chromatography(HPLC) was used to yield 12 compounds.Through spectral data analysis and comparison with previous reports, they were identified as methyl(E)-5-hydroxymethyl-6,7-dihydroxy-4,5-epoxy-octanoate-2-ene(1),(2E,6E)-nona-2,6,8-triene-4,5-diol(2), 8-O-(R)-methoxynodulisporin A(3), 3-nitropropionic acid(4), 3-nitropropionic acid methyl ester(5), 3,4-dihydroxy-phenylethanol(6), 2,4-dichlorobenzoic acid(7), cis-4-hydroxyscytalone(8), 4,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one(9), isosclerone(10), 4H-1-benzopyran-4-one-2,3-dihydro-5-hydroxy-8-(hydroxyl-methyl)-2-methy(11), and 5-methylmellein(12), respectively.Compounds 1 and 2 were identified for the first time.In vitro cytotoxicity test indicated that compounds 1-12 had no significant inhibitory effect on A549 and HepG2 cells.Antimicrobial susceptibility testing revealed that compound 3 showed synergistic effect with the positive control chloramphenicol.

[Rapid health technology assessment of four oral Chinese patent medicines for constipation].

This study evaluated the safety, efficacy, and cost effectiveness of Biantong Capsules(Tablets), Maren Runchang Pills, Qirong Runchang Oral Liquid, and Qihuang Tongmi Soft Capsules in the treatment of constipation by the rapid health technology assessment(RHTA) to provide evidence for clinical decision and references for rapid evaluation of Chinese patent medicine(CPM). CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Web of Science, and Cochrane Library were searched for research articles from database inception to February 2022. Two reviewers conducted literature screening, data extraction, and quality evaluation according to the predetermined standards. Descriptive analysis of the results combined with visual charts was performed. Sixty research articles were included, involving 44 randomized controlled trials(RCTs), 7 clinical controlled trials(CCTs), 4 systematic reviews/Meta-analyses, and 5 economic analysis studies. As revealed by the results, Biantong Capsules(Tablets) could be used for postoperative and senile constipation, in which some studies reported Biantong Capsules(Tablets) were superior to Maren Runchang Pills and Qirong Runchang Oral Liquid. Maren Runchang Pills were mainly used for senile constipation, and the efficacy was similar to that of conventional wes-tern medicine, but the cost was low and the compliance of patients was good. Qirong Runchang Oral Liquid was indicated for disease-derived or drug-induced constipation, chronic constipation, and senile constipation with fewer adverse reactions. Qihuang Tongmi Soft Capsules had good efficacy and safety in the treatment of functional constipation. Overall, compared with western medicine glycerine enema and lactulose, the number of clinical studies of the four CMPs was small, but they targeted constipation patients with different subtypes. In conclusion, the four CMPs have their advantages and characteristics in the treatment of constipation, but they are restric-ted by sparse existing evidence, low quality of evidence, and insufficient economic research. In the future, more high-quality and long-term follow-up studies should be carried out to obtain reliable evidence. Meanwhile, it is called for strengthening the economic evaluation of CMPs to provide evidence for decision-making.

WITHDRAWN: Discovery of indoline derivatives as anticancer agents via inhibition of tubulin polymerization.

Human esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in human digestive system. It is necessary to discover novel antitumor agents for the treatment of esophageal cancers because of its poor prognosis. Indoline has been reported as an efficient anticancer fragment to design novel anticancer agents. In this work, indoline derivatives were designed, synthesized and explored their anticancer activity. Compound 9d, which exhibited potent antiproliferative activity with IC50 values of 1.84 µM (MGC-803 cells), 6.82 µM (A549 cells), 1.61 µM (Kyse30 cells), 1.49 µM (Kyse450 cells), 2.08 µM (Kyse510 cells) and 2.24 µM (EC-109 cells), respectively. The most active compound 9d was identified as a tubulin inhibitor targeting colchicine binding site with an IC50 value of 3.4 µM. Compound 9d could strongly suppress the tubulin polymerization in Kyse450 cells. The results of molecular docking also suggested compound 9d could tightly bind into the colchicine binding site of ß-tubulin. Besides, compound 9d inhibited the growth of KYSE450 cells in time and dose-dependent manners. All the results suggest that the indoline derivatives might be a class of novel tubulin inhibitors with potential anticancer activity and is worthy of further study.

Discovery of indoline derivatives as anticancer agents via inhibition of tubulin polymerization.

Human esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in human digestive system. It is necessary to discover novel antitumor agents for the treatment of esophageal cancers because of its poor prognosis. Indoline has been reported as an efficient anticancer fragment to design novel anticancer agents. In this work, indoline derivatives were designed, synthesized and explored their anticancer activity. Compound 9d, which exhibited potent antiproliferative activity with IC50 values of 1.84 µM (MGC-803 cells), 6.82 µM (A549 cells), 1.61 µM (Kyse30 cells), 1.49 µM (Kyse450 cells), 2.08 µM (Kyse510 cells) and 2.24 µM (EC-109 cells), respectively. The most active compound 9d was identified as a tubulin inhibitor targeting colchicine binding site with an IC50 value of 3.4 µM. Compound 9d could strongly suppress the tubulin polymerization in Kyse450 cells. The results of molecular docking also suggested compound 9d could tightly bind into the colchicine binding site of tubulin. Besides, compound 9d inhibited the growth of KYSE450 cells in a time and dose-dependent manner. All the results suggest that the indoline derivatives may be a class of novel tubulin inhibitors with potential anticancer activity, and which is worthy of further study.

Risk factors of postoperative adhesive bowel obstruction in children with complicated appendicitis.

PURPOSE: Postoperative adhesive bowel obstruction (ABO) is a common complication especially in complicated appendicitis. This study aimed to analyze the risk factors for ABO following appendectomy in children with complicated appendicitis, and establish a scoring model for predicting postoperative ABO and treatment option to relieve the obstruction. METHODS: From December 2014 to January 2020, all files of consecutive patients with complicated appendicitis underwent appendectomy were reviewed. Univariate and multivariate analyses were used to screen out the risk factors of postoperative ABO, and establish a scoring model for predicting postoperative ABO and surgical relief to relieve the obstruction. RESULTS: Of the 780 patients, 87 (11.2%) had ABO following appendectomy, including 27 who underwent surgical relief. Age ≤ 6 years, overweight and obesity, duration of symptoms ≥ 36 h, C-reactive protein ≥ 99 mg/L, duration of operation ≥ 60 min, intraoperative peritoneal lavage, and postoperative flatus time ≥ 20 h were independent risk factors for postoperative ABO. The final scoring model for postoperative ABO included factors above, and exhibited a high degree of discrimination (area under the curve [AUC]: 0.937; 95% confidence interval [CI] 0.913-0.960) corresponding to an optimal cut-off value of 6: 82.8% sensitivity, 92.6% specificity. Furthermore, the scoring model showed a sensitivity of 74.1% and a specificity of 91.7% for patients wo underwent surgical relief to relieve obstruction with the optimal cut-off value of 9. CONCLUSION: Risk factors for postoperative ABO should be taken seriously in children with complicated appendicitis. The scoring model is a novel but promising method to predict postoperative ABO and provide reference for clinical decision-making to relieve the obstruction.

[Four new lanostane triterpenoids from latex of Euphorbia resinifera].

Four new lanostane triterpenoids, 3ß-hydroxy-12α-methoxylanosta-7,9(11),24-triene(1), 3ß-hydroxy-12α-methoxy-24-methylene-lanost-7,9(11)-dien(2), 3,7-dioxo-lanosta-8,24-diene(3), and 3,7-dioxo-24-methylene-lanost-8-en(4), were isolated from the latex of Euphorbia resinifera with a variety of chromatography methods. Their structures were elucidated based on spectroscopic data and/or comparison with the data reported in previous research. Compounds 1, 2, and 4 showed moderate inhibition of LPS-induced NO production by RAW264.7, with IC_(50) of 30.4, 37.5, and 28.3 µmol·L~(-1), respectively.

A clinical prediction model for complicated appendicitis in children younger than five years of age.

BACKGROUND: No reliably specific method for complicated appendicitis has been identified in children younger than five years of age. This study aimed to analyze the independent factors for complicated appendicitis in children younger than five years of age, develop and validate a prediction model for the differentiation of simple and complicated appendicitis. METHODS: A retrospective study of 382 children younger than five years of age with acute appendicitis from January 2007 to December 2016 was conducted with assessments of demographic data, clinical symptoms and signs, and pre-operative laboratory results. According to intraoperative findings and postoperative pathological results, acute appendicitis was divided into simple and complicated appendicitis. Univariate and multivariate analyses were used to screen out the independent factors of complicated appendicitis, and develop a prediction model for complicated appendicitis. Then 156 such patients from January 2017 to December 2019 were collected as validation sample to validate the prediction model. Test performance of the prediction model was compared with the ALVARADO score and Pediatric Appendicitis Score (PAS). RESULTS: Of the 382 patients, 244 (63.9%) had complicated appendicitis. Age, white blood cell count, and duration of symptoms were the independent factors for complicated appendicitis in children younger than five years of age. The final predication model for complicated appendicitis included factors above. In validation sample, the prediction model exhibited a high degree of discrimination (area under the curve [AUC]: 0.830; 95% confidence interval [CI]: 0.762-0.885) corresponding to a optimal cutoff value of 0.62, and outperformed the PAS (AUC: 0.735; 95% CI: 0.658-0.802), ALVARADO score (AUC: 0.733; 95% CI: 0.657-0.801). CONCLUSION: Age, white blood cell count, and duration of symptoms could be used to predict complicated appendicitis in children younger than five years of age with acute appendicitis. The prediction model is a novel but promising method that aids in the differentiation of acute simple and complicated appendicitis.