To explore the chemical constituents of Ecballium elaterium and their cytotoxicity, this study employed multiple chromatographic techniques including normal-phase silica gel, MCI, octadecylsilyl(ODS), Sephadex LH-20 gel, and semi-preparative liquid chromatography for compound isolation from its active fraction. A total of 12 compounds were obtained, and they were identified according to the analysis of a variety of spectral data and literature comparison as 24Z-20,27-dihydroxy-16α,23α-epoxy-cucurbita-2-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside(1), cucurbitacin R(2), cucurbitacin B(3), cucurbitacin D(4), cucurbitacin I(5), cucurbitacin L(6), dehydrodiconiferyl alcohol(7), 3-hydroxy-4-methoxycinnamic acid(8), ferulaic acid(9), p-coumaric acid(10), rutin(11), and lariciresinol-4'-O-β-D-glucoside(12), among which compound 1 was a new compound. Compounds 2-6 had strong cytotoxicity against human lung carcinoma A549 cells with the IC_(50) values of(0.48±0.09),(0.03±0.002),(0.13±0.03),(0.87±0.14),(0.15±0.03) μmol·L~(-1), respectively, which were stronger than the positive control doxorubicin \[IC_(50)=(3.92±1.60) μmol·L~(-1)\].
Humans ; Drugs, Chinese Herbal/toxicity* ; Cell Line, Tumor ; Cucurbitaceae/chemistry* ; Cell Survival/drug effects*

Three taraxerane nortriterpenoids were isolated from mastic by using various modern chromatographic separation techniques. They were identified as(5R,8R,9R,10S,11S,12R,13S,17R,18R)-28-norlupa-11,12-epoxy-14-taraxerene-3,16-dione(1),(5R,8R,9R,10S,11S,12R,13S,17S,18S)-17-hydroxy-28-norlupa-11,12-epoxy-14-taraxerene-3-one(2), and(5R,8R,9R,10R,11S,12R,13R,14S,17S,18S)-14,17-epoxy-28-norlupa-11,12-oxidotaraxerone(3) through the high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), infrared(IR), ultraviolet(UV), nuclear magnetic resonance(NMR), and single-crystal X-ray diffraction techniques as well as comparison with literature data. Compounds 1-3 were C-28 nortriterpenoids and isolated from mastic for the first time, and compounds 1-2 were new ones. In the model for RAW264.7 cell anti-inflammation induced by lipopolysaccharide(LPS), compound 1 demonstrates an inhibitory effect on nitric oxide(NO) [IC_(50)=(13.38±0.68) μmol·L~(-1)], comparable to the activity of the positive control dexamethasone [IC_(50)=(14.59±1.49) μmol·L~(-1)]. Compounds 2 and 3 exhibit weaker inhibitory effects, with IC_(50) values of(24.17±2.56) and(22.25±2.84) μmol·L~(-1), respectively.
Animals ; Mice ; Triterpenes/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Mastic Resin/chemistry* ; Nitric Oxide ; Molecular Structure ; Macrophages/immunology* ; RAW 264.7 Cells

Objective To observe the efficacy of occlusive dressing therapy combined with infra-red lamp irradiation on skin lesions in patients with synovitis-acne-pustulosis-hyperostosis-osteomyeli-tis(SAPHO)syndrome.Methods A total of 52 patients with SAPHO syndrome were selected as study subjects.They were randomly divided into control group and observation group using random number table method,with 26 patients in each group.The control group received conventional treat-ment,while the observation group received occlusive dressing therapy combined with infrared lamp ir-radiation on the basis of the control group.The skin lesion scores,Dermatology Life Quality Index(DLQI)scores,Self-rating Anxiety Scale(SAS)scores,and Self-rating Depression Scale(SDS)scores of the two groups were compared.The clinical efficacy and adverse reactions of the two groups were also statistically analyzed.Results One and two months after treatment,the skin lesion scores of both groups were lower than those before treatment,and the scores in the observation group were lower than those in the control group(P＜0.05).After treatment,the DLQI,SAS,and SDS scores of both groups were lower than those before treatment,and the scores in the observation group were lower than those in the control group(P＜0.05).The total effective rate in the observation group was 96.15％,which was higher than 80.77％ in the control group(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Con-clusion Occlusive dressing therapy combined with infrared lamp irradiation can significantly improve the symptoms of skin lesions and the psychological state of patients with SAPHO syndrome,as well as enhance their quality of life and the therapeutic effect of the disease.

Objective: To analyze the trends in disease burden of tuberculosis among children under 5 years of age in China from 1990 to 2021, so as to provide insights for future tuberculosis control measures among children in China. Methods: Based on the Global Burden of Disease (GBD) 2021 datasets, the incidence, prevalence, mortality and disability adjusted life year(DALY) of tuberculosis of children under 5 years of age in China and globally were collected from 1990 to 2021. The incidence, prevalence, mortality and DALY rate of tuberculosis were compared by genders and types. In addition,the annual percent change(APC) and the average annual percent change(AAPC) of children s tuberculosis burden in China and globally from 1990 to 2021 were calculated by using the Joinpoint regression model, and the changing trends were analyzed. Results: The numbers of incident, prevalent and dead tuberculosis cases were 9 700, 8 477 800 and 200 among children under 5 years of age in China in 2021, and the DALY due to tuberculosis were 27 100 person years. There were significant reductions in incidence, prevalence, mortality and DALY rate of tuberculosis among children under 5 years of age in China ( AAPC =-5.45%, -1.14%, -12.37%, -11.34 %) and globally( AAPC =-2.38%, -1.41%, -4.66%, -4.56%), and the reductions in the incidence, mortality and DALY rate were more significant in China than globally ( P <0.05).In 1992 and later, the numbers of incident, prevalent and dead tuberculosis cases and the DALY of tuberculosis were higher among male than among female. In addition, the disease burden of drug susceptible tuberculosis appeared a tendency of downward in China from 1990 to 2021, while the incidence and prevalence of extensively drug resistant tuberculosis rose since 2015. Conclusions The disease burden of tuberculosis remarkably reduced among children under 5 years of age in China from 1990 to 2021. However, the burden of disease due to multidrug resistant tuberculosis appeared an upward trend recently. Increased attention is required to be paid to the prevention and control of tuberculosis among children and improved diagnosis and treatment of drug resistant tuberculosis are recommended.

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

Ten compounds were separated by various modern chromatographic methods from mastic. They were identified by HR-ESI-MS, IR, UV, NMR, quantum chemical calculation of NMR(qcc-NMR) and comparison with reported data in literature as 17β-hydroxy-28-norolean-18-en-3-one(1), 28-norolean-12,17-dien-3,11-dione(2), 28-norolean-16,18-dien-3-one(3),(24Z)-26-hydroxy-7,24-dientirucalla-3-one(4), masticadienonic acid(5)、masticadienolic acid(6)、erythrodiol(7), 3β,28-dihydroxyoleana-11,13(18)-diene(8), 3-oxo-olean-9(11),12-dien-28-oic acid(9), and 12-oleane-3,11-dione(10). Among them, compound 1 was a novel compound and compound 2 was a novel natural product. Compounds 1-2, 4, and 7-9 were isolated from mastic for the first time. Compound 1 significantly inhibited lipopolysaccharide-induced production of nitric oxide in mouse monocyte macrophage RAW264.7 cells with the IC_(50) of(7.44±0.49) μmol·L~(-1), which was more potent than the positive control, dexamethasone \[IC_(50)=(9.93±1.17) μmol·L~(-1)\]. Compounds 2-3, 5, and 9-10 also showed inhibitory effects, with the IC_(50) ranging from 14.82 to 28.82 μmol·L~(-1). Compounds 4-5, and 7 markedly inhibited the growth of human colon adenocarcinoma cells SW480, with the IC_(50) of(16.13±1.69),(27.40±1.81), and(10.01±0.10) μmol·L~(-1), respectively.
Mice ; Animals ; Mastic Resin/chemistry* ; Humans ; Macrophages/metabolism* ; Triterpenes/isolation & purification* ; Nitric Oxide ; Molecular Structure ; RAW 264.7 Cells ; Drugs, Chinese Herbal/isolation & purification*

To elucidate the chemical material basis of Rhododendron nivale, this study comprehensively used various chromatographic techniques to isolate and obtain five new meroterpenoid enantiomers(1a/1b-5a/5b) from the ethyl acetate extract of R. nivale. A variety of spectral analytical methods, such as high-resolution mass spectrometry(HRMS), nuclear magnetic resonance spectroscopy(NMR), and infrared(IR) spectrum, were used to evaluate the structure, combined with the measurement and calculation of electronic circular dichroism(ECD). The new compounds 1a/1b-4a/4b were named as(±)-nivalones A-B(1a/1b-2a/2b) and(±)-nivalnoids C-D(3a/3b-4a/4b), along with one known enantiomer(±)-anthoponoid G(5a/5b). Human neuroblastoma cells(SH-SY5Y cells) induced by hydrogen peroxide(H_2O_2) were used as oxidative stress models to evaluate the protective activity of the isolated compounds against oxidative damage to nerve cells. It was found that compounds 2a and 3a had a certain protective effect on nerve cells against H_2O_2-induced oxidative damage at concentrations of 50 μmol·L~(-1), which increased the cell survival rate from 44.02%±2.30% to 67.82%±1.12% and 62.20%±1.87%, respectively. Other compounds did not show a significant ability to protect cells from oxidative damage. These findings enrich the chemical constituents of R. nivale and provide valuable information for identifying the structure of its meroterpenoids.
Humans ; Rhododendron/chemistry* ; Neuroblastoma ; Oxidative Stress ; Magnetic Resonance Spectroscopy ; Stereoisomerism ; Molecular Structure

This study aims to identify the chemical constituents from Callicarpa kwangtungensis and determine their activities. MCI, ODS, and Sephadex LH-20 chromatography and semi-preparative HPLC were employed to separate the chemical constituents. A total of 15 compounds were separated, and their structures were identified on the basis of spectroscopic analysis and comparison with the data in relevant literature. Specifically, the 15 compounds were 3-O-α-L-rhamnopyranosyl-6-O-β-D-apiofuranosyl-4-O-E-caffeoyl-D-glucopyranoside(1), 3,6-O-α-L-dirhamnopyranosyl-4-O-E-caffeoyl-D-glucopyranoside(2), β-OH-forsythoside B(3), β-OH-poliumoside(4),(+)-lyoniresinol-3α-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside(5),(+)-lyoniresinol-3α-O-β-D-glucopyranoside(6),(-)-lyoniresinol-3α-O-β-D-glucopyranoside(7), kelampayoside A(8), descaffeoylpoliumoside(9), acteoside(10), alyssonoside(11), poliumoside(12), isacteoside(13), acetyl forsythoside B(14), and forsythoside B(15). Compounds 1 and 2 were novel, and the NMR data of compounds 3 and 4 were reported here for the first time. Furthermore, the hemostatic activities of the extract and abundant ingredients(compounds 12 and 15) of C. kwangtungensis were determined with Yunnan Baiyao as the positive control and normal saline as the negative control. The extract and compounds 12 and 15 significantly shortened the tail tip bleeding time in mice.
Animals ; Mice ; Callicarpa ; Hemostatics ; China ; Glycosides/chemistry*

Objective This study reconstructed 4D-CBCT for fully automatic compensated sliding motion by incorporating the bilateral filtering into the Deformable Vector Field (DVF). Methods First, a motion compensated simultaneous algebraic reconstruction technique (Modified Simultaneous Algebra Reconstruction Technique, mSART) was used to generate a high quality reference phase by using all phase projection stogether with the initial 4D-DVFs, which were generated via Demons registration between 0% phase and each other phaseimage. The 4D-DVF was optimized by matching the forward projection of the deformed 0% phase with the measured projection of the target phase. The loss function’s DVF smoothing constrain term contained bilateral filtering kernel that contained: 1) an spatial domain Guassian kernel; 2) animage intensity domain Guassian kernel; and 3) a DVF domain Guassian kernel. By choosing suitable kernel variances, the sliding motion can be extracted. A non-linear conjugate gradient optimizer wasused. We validated the algorithm on a Non-Uniform Rotational B- spline based Cardiac-Torso (NCAT) phantom. Quantification was evaluated by: 1) the Root-Mean-Square-Error (RMSE) together with the Maximum-Error (MaxE); 2) the Dice coefficient of the extracted lung contour from the final reconstructed images and 3) the relative reconstruction error (RE) to evaluate the algorithm's performance. Results The motion trajectory's RMSE/MaxEare 0.796/1.02 mm for bilateral filtering reconstruction; and 2.704/4.08 mm for original reconstruction. Image content such a stherib position, the hearted gedefinition, the fibrous structures all had been better corrected with bilateral filtering. Conclusion We developed a bilateral filtering based fully automatic sliding motion compensated 4D-CBCT scheme. Digital phantom study confirmed the improved motion estimation and image reconstruction ability. It can be used as a 4D-CBCT image guidance tool for lung SBRTtreatment.

Four new lanostane triterpenoids, 3β-hydroxy-12α-methoxylanosta-7,9(11),24-triene(1), 3β-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.
Euphorbia ; Latex ; Molecular Structure ; Steroids ; Triterpenes