Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.
Computational Biology ; Drugs, Chinese Herbal ; Humans ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Urinary Bladder Neoplasms/genetics*

OBJECTIVE To establish the fingerprints of Ligusticum sinense from different habitats ，screen differential components and determine their contents. METHODS Using Z-ligustilide as reference ，HPLC fingerprints of 12 batches of L. sinense were established by using Similarity Evaluation System of Chromatographic Fingerprints of TCM （2012 edition）；common peaks were identified and their similarities were evaluated. Cluster analysis （CA），principal component analysis （PCA）and orthogonal partial least squares-discriminant analysis （OPLS-DA）were performed to screen differential components with variable importance in the projection （VIP）＞1 as standard ；meanwhile，the contents of above differential components were determined by the same HPLC method. RESULTS There were 17 common peaks in the fingerprints of 12 batches of L. sinense ，and their similarities ranged 0.989-1.000. A total of 9 common peaks were identified ，i.e. chlorogenic acid （peak 1），ferulic acid （peak 2）， senkyunolide Ⅰ（peak 7），coniferyl ferulate （peak 9），E-ligustilide（peak 13），senkyunolide A （peak 14），Z-ligustilide（peak 17）. CA results showed that 12 batches of L. sinense were divided into 3 categories，S1-S5（Wuning）were clustered into one category，S6-S8（Ruichang）were clustered into one category ，S9-S12（De’an）were clustered into one category ；the VIP values of peaks 2，13，14 and 17（corresponding to ferulic acid ，E-ligustilide，senkyunolide A ，and Z-ligustilide respectively ）were all greater than 1，respectively. In S 1-S5，S6-S8 and S 9-S12 samples，the contents of ferulic acid were 0.488-0.533，0.603-0.658 and 0.415-0.433 mg/g，respectively；senkyunolide A were 1.184-1.295，1.450-1.588 and 1.307-1.377 mg/g，respectively；E-ligustilide were 0.118-0.125，0.130-0.135 and 0.223-0.229 mg/g，respectively；Z-ligustilide were 7.200-7.681，8.076-8.643 and 4.508-4.996 mg/g， respectively；the differences between two groups were statisti-cally significant （P＜0.05）. CONCLUSIONS Established ARS-11）；fingerprint is simple and accurate ，and can be used for overall quality evaluation of L. sinense from different habitats by combining with multivariate statistical analysis. Ferulic acid ， senkyunolide A ，Z-ligustilide and E-ligustilide may be the differential components that affect the quality of L. sinense from different habitats ，the contents of the first 3 components in L. sinense from Ruichang are the highest ，and the content of E-ligustilide in samples from De’an is the highest.

BACKGROUND: Exposure to the ionizing radiation (IR) encountered outside the magnetic field of the Earth poses a persistent threat to the reproductive functions of astronauts. The potential effects of space IR on the circadian rhythms of male reproductive functions have not been well characterized so far. METHODS: Here, we investigated the circadian effects of IR exposure (3 Gy X-rays) on reproductive functional markers in mouse testicular tissue and epididymis at regular intervals over a 24-h day. For each animal, epididymis was tested for sperm motility, and the testis tissue was used for daily sperm production (DSP), testosterone levels, and activities of testicular enzymes (glucose-6-phosphate dehydrogenase (G6PDH), sorbitol dehydrogenase (SDH), lactic dehydrogenase (LDH), and acid phosphatase (ACP)), and the clock genes mRNA expression such as Clock, Bmal1, Ror-α, Ror-β, or Ror-γ. RESULTS: Mice exposed to IR exhibited a disruption in circadian rhythms of reproductive markers, as indicated by decreased sperm motility, increased daily sperm production (DSP), and reduced activities of testis enzymes such as G6PDH, SDH, LDH, and ACP. Moreover, IR exposure also decreased mRNA expression of five clock genes (Clock, Bmal1, Ror-α, Ror-β, or Ror-γ) in testis, with alteration in the rhythm parameters. CONCLUSION These findings suggested potential health effects of IR exposure on reproductive functions of male astronauts, in terms of both the daily overall level as well as the circadian rhythmicity.
ARNTL Transcription Factors/genetics* ; Acid Phosphatase ; Animals ; CLOCK Proteins/genetics* ; Circadian Rhythm/radiation effects* ; Epididymis/radiation effects* ; Gene Expression/radiation effects* ; Genitalia, Male/radiation effects* ; Glucosephosphate Dehydrogenase ; L-Iditol 2-Dehydrogenase ; L-Lactate Dehydrogenase ; Male ; Mice ; Mice, Inbred C57BL ; Models, Animal ; Nuclear Receptor Subfamily 1, Group F, Member 1/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 2/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics* ; RNA, Messenger/genetics* ; Radiation Exposure ; Radiation, Ionizing ; Reproductive Physiological Phenomena/radiation effects* ; Sperm Motility/radiation effects* ; Spermatozoa/radiation effects* ; Testis/radiation effects*

OBJECTIVE: To carry out G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA) for a fetus featuring multiple malformations. METHODS: The fetus was found to have increased nuchal thickness, generalized edema, asymmetric lower limbs, tetralogy of Fallot, nasal bone anomaly and cleft palate. Following amniocentesis, G-band karyotyping and CMA were carried out. RESULTS: The fetus had a karyotype of 47,XX,+i(12)(p10) [14]/46,XX[6]. CMA has identified a 33.9 Mb duplication at 12p13.33-p11.1, which was suggestive of tetrasomy 12p. CONCLUSION Combined chromosomal karyotyping and CMA can delineate the origin of abnormal chromosomal fragments during prenatal diagnosis. The fetus was diagnosed with Pallister-Killian syndrome.

In order to study the pesticide residues of the medicinal Crataegi Fructus,this study aims to establish an analysis method for pesticide residues( mainly containing insecticides and fungicides) suitable for the actual situation of medicinal Crataegi Fructus based on the survey of the pesticides of the Crataegi Fructus base,combined with the blind screening results of the LC-ESI-MS/MS pesticide screening platform established by the research team in the early stage. Then,the pesticide residues in medicinal Crataegi Fructus from Shandong,Hebei,Henan,Shanxi,and Liaoning( main cultivation areas) were analyzed. The samples were pretreated by the modified Qu ECh ERS method,i.e.,extracted with acetonitrile-water( 9 ∶1),purified by PSA,C_(18),GCB,silica gel. The detection of pesticides was performed by LC-MS/MS. The ion source was ESI with positive scanning mode,and the linearity of 11 kinds of pesticides in the range of 5-300 μg·kg~(-1) was acceptable( R~2>0. 996 9). All the recoveries of pesticides were within 70. 02%~(-1)12. 0% in the low,medium and high levels,with RSD≤17%. The results showed that the detection rate of carbendazim,chlorpyrifos and difenoconazole is 79%,82%,56%,respectively. Besides,the prohibition pesticide carbofuran were detected in some of the batches,indicating the security risk. This study provides methodological references and basic data for risk assessment of Crataegi Fructus and government regulation.
Chromatography, Liquid ; Crataegus/chemistry* ; Drug Contamination ; Drugs, Chinese Herbal/analysis* ; Pesticide Residues/analysis* ; Surveys and Questionnaires ; Tandem Mass Spectrometry

Objective To evaluate the effect of endoscopic management of foreign bodies in the upper digestive tract. Methods Clinical data and endoscopic treatment methods of 41 patients were retrospectively analyzed from October 2014 to May 2016. Patients with incomplete medical records were excluded. Results Foreign bodies in the upper digestive tract occurred high frequency in elderly. 53.6% of the foreign bodies were located in the esophagus. Date stones was the main type of foreign bodies (56.1%). 41 cases with foreign bodies in digestive tract were successfully extracted, while 1 case occurred perforation. Conclusion Endoscopic management of gastrointestinal foreign bodies is safe and effective.

Objective To explore the clinical significance of detection of plasma microRNA-21,-143 in identifying early esophageal cancer and esophageal non-tumor diseases.Methods The expression of plasma microRNA-21,-143 in 27 cases of patients with early esophageal cancer (esophagus cancer group),25 cases of patients with non-esophageal tumor (non-esophageal tumor group)and in the healthy controls were detected by RT-PCR,and detected the levels of plasma CEA and CA72-4 by the electrochemical luminescence technology,which of changes were analysed to observe the relationship between the changes and the esophageal cancer,the benign esophageal diseases for the two markers.Results The expression of plasma microRNA-21,-143 in the esophagus cancer group were 0.93±0.17,0.27±0.05,which of ones in the non-esophagus cancer group were 0.25±0.03,0.99±0.15,and with those in the control group were 0.23±0.03,1.02±0.15.Compared with those in the non-esophagus cancer group,the expression of plasma microRNA-21,-143 were obviously up or down-regulated with significant differences (t=10.87,11.55,P＜0.01).Compared with those in the control group,which of ones were obviously up or down-regulated with significant differences (t=9.20,9.07,P＜0.01),and with no statistical significances in comparison between the esophagus cancer group and the control group (t=1.39,1.19,P＞0.05).The positiverate of plasma microRNA-21,-143 in the esophageal cancer,non-esophagus cancer group and the control group were,81.4 ％ (22/27),4.0 ％(1/25) and 0 (0/24);85.1％ (23/27),4.0％ (1/25),and 0 (0/24),respectively.The positive rate of microRNA-21,-143 in the esophageal group respectively in comparison with those in the non-esophagus cancer group and the control group were significantly higher,the differences had statistical significances (x2 =31.59,34.39,P＜ 0.01;x2 =34.42,37.23,P＜ 0.01).The expression of two markers in the esophagus cancer group were no statistically significant differences compared with control group (x2 =0.980,0.980,P＞0.05).The sensitivity and specificity of microRNA-21,-143 in early diagnosis on the esophageal cancer were 81.4 ％,97.9 ％ and 85.1％,97.9 ％.The sensitivity of microRNA-21,-143 in the esophageal group were significantly higher compared with those of CEA and CA72-4,the differences were statistically significant (x2 =12.79,P＜0.01;x2 =5.33,P＜0.05;x2 =15.03,P＜0.01;x2 =6.95,P＜0.05).The specificity of microRNA-21,-143 in the esophageal cancer group were no statistically significant differences in comparison with those of CEA and CA72-4 (x2 =1.043,0.000,P＞0.05) and (x2=1.043,0.000,P＞0.05),respectively.The analysis results from the spearman correlation test showed that in the esophageal cancer group,the expression of plasma microRNA-21,-143 had a negative correlation (r =0.658,P＜0.01).Which of ones respectively associated with the levels of CEA and CA72-4 (r=0.607,0.623,P＜0.01 and r=0.579,0.610,P＜0.01).Conclution The detection of expression of plasma miRNA-21,miRNA-143 in the patients with the early esophageal cancer and non-esophageal tumor can provide a new train of thought for pathologic diagnosis of early esophageal cancer.

Objective To establish an HPLC method for simultaneous separation and determination of chlorogenic acid, quercetin and kaempferol inPyrrosia lingua (Thumb.) Farwell. Methods The separation was performed on Phenomenex C18 column (250 mm×4.6 mm, 5μm) with the mobile phase of methanol-acetic acid (pH=3.0) solution and gradient elution. Flow rate was 1.0 mL/min;the UV detection wavelength was 254 nm;column temperature was 35℃.Results The calibration curves for chlorogenic acid, quercetin, and kaempferol were in good linearity in the range of 0.000 24-3.00μg (r=0.999 9), 0.000 16-2.00μg (r=0.999 9), and 0.000 16-2.00μg (r=0.999 9), respectively. The limits of detection (S/N=3) were 3.29, 0.43 and 0.33 ng/mL, respectively. The average recovery rates were 97.73%, 98.07% and 96.92%, respectively. ConclusionThe method is simple, precise and sensitive. It provides scientific proof for separation and determination of chlorogenic acid, quercetin and kaempferol inPyrrosia lingua (Thumb.) Farwell.