Objective:To establish a three-dimensional (3D) U-net-based deep learning model, and to predict the 3D dose distribution in CT-guided cervical cancer brachytherapy by using the established model.Methods:The brachytherapy plans of 114 cervical cancer cases with a prescription dose of 6 Gy for each case were studied. These cases were divided into training, validation, and testing groups, including 84, 11, and 19 patients, respectively. A total of 500 epochs of training were performed by using a 3D U-net model. Then, the dosimetric parameters of the testing groups were individually evaluated, including the mean dose deviation (MDD) and mean absolute dose deviation (MADD) at the voxel level, the Dice similarity coefficient (DSC) of the volumes enclosed by isodose surfaces, the conformal index (CI) of the prescription dose, the D90 and average dose Dmean delivered to high-risk clinical target volumes (HR-CTVs), and the D1 cm 3 and D2 cm 3 delivered to bladders, recta, intestines, and colons, respectively. Results:The overall MDD and MADD of the 3D dose matrix from 19 cases of the testing group were (-0.01 ± 0.03) and (0.04 ± 0.01) Gy, respectively. The CI of the prescription dose was 0.70 ± 0.04. The DSC of 50%-150% prescription dose was 0.89-0.94. The mean deviation of D90 and Dmean to HR-CTVs were 2.22% and -4.30%, respectively. The maximum deviations of the D1 cm 3 and D2 cm 3 to bladders, recta, intestines, and colons were 2.46% and 2.58%, respectively. The 3D U-net deep learning model took 2.5 s on average to predict a patient′s dose. Conclusions:In this study, a 3D U-net-based deep learning model for predicting 3D dose distribution in the treatment of cervical cancer was established, thus laying a foundation for the automatic design of cervical cancer brachytherapy.

Objective:To investigate the improvement effects of duodenal-jejunal bypass (DJB)on the blood glucose homeostasis,insulin resistance and inflammation of the obese type 2 diabetic (T2DM)ZDF rats,and to discuss its possible mechanism.Methods:A total of 20 ZDF rats were randomly divided into DJB operation group and sham operation group (n = 10).There were 8 rats survived in each group after operation.The level of blood glucose (FBG)was detected by Roche glucose meter at 1 week before operation,2 weeks,4 weeks and 6 weeks after operation;the fasting serum insulin level of the rats was measured by ELISA kit;the insulin sensitivity index (HOMA-ISI)and insulin resistance index (HOMA-IR)were calculated.The rats were executed 6 weeks after operation.HE staining was used to observe the morphology of the inflammatory cells in BP limb of the rats;the expression levels of AMPK and pAMPK in BP lamb of the rats were observed by immunohistochemical staining;the expression levels of interleukin 1β(IL-1β),interleukin 6 (IL-6),tumor necrosis factorα(TNF-α),nuclear factorκB (NF-κB),and interleukin 10 (IL-10)mRNA of the rats were detected by QRT-PCR method.Results:From the 2nd week after operation,compared with before operation,the FBG levels of the rats in DJB operation group were decreased (t=3.798,P <0.05);compared with sham operation group,the FBG level of the rats in DJB operation group was decreased (t=3.205,P <0.05).Six weeks after operation,compared with sham operation group,the HOMA-IR of the rats in DJB operation group was significantly decreased (t=4.441,P <0.05)and the HOMA-ISI was significantly increased (t=-8.65,P < 0.05).The HE staining results showed that compared with sham operation group,the morphology of the inflammatory cells in BP limb of the rats in DJB operation group was significantly improved.The QRT-PCR results showed that the expression levels of IL-1β,IL-6,TNF-αand NF-κB of the rats in DJB operation group was significantly decreased compared with sham operation group (P < 0.05), while the expression level of IL-10 was significantly increased (P < 0.05).The immunohistochemical test results showed that the expression levels of AMPK and pAMPK in BP lamb of the rats in DJB operation group were increased compared with sham operation group.Conclusion:DJB can significantly improve the blood glucose homeostasis and insulin resistance in the T2DM rats,and its mechanism may be related to the decreased expressions of inflammatory factors and the activation of AMPK molecules in BP lamb of the T2DM rats.

Heme is a key cofactor in aerobic life, both in eukaryotes and prokaryotes. Because of the high reactivity of ferrous protoporphyrin IX, the reactions of heme in cells are often carried out through heme-protein complexes. Traditionally studies of heme-binding proteins have been approached on a case by case basis, thus there is a limited global view of the distribution of heme-binding proteins in different cells or tissues. The procedure described here is aimed at profiling heme-binding proteins in mouse tissues sequentially by 1) purification of heme-binding proteins by heme-agarose, an affinity chromatographic resin; 2) isolation of heme-binding proteins by SDS-PAGE or two-dimensional electrophoresis; 3) identification of heme-binding proteins by mass spectrometry. In five mouse tissues, over 600 protein spots were visualized on 2-DE gel stained by Commassie blue and 154 proteins were identified by MALDI-TOF, in which most proteins belong to heme related. This methodology makes it possible to globally characterize the heme-binding proteins in a biological system.
Animals ; Carrier Proteins ; biosynthesis ; genetics ; Electrophoresis, Gel, Two-Dimensional ; Electrophoresis, Polyacrylamide Gel ; Heme ; chemistry ; Hemeproteins ; biosynthesis ; genetics ; Mass Spectrometry ; Mice ; Mice, Inbred ICR ; Protein Binding ; Proteins ; chemistry ; Proteome ; Proteomics ; methods ; Sepharose ; chemistry ; Tissue Distribution

Objective:To provide a basis for selecting the optimization method for intracavitary/interstitial brachytherapy (IC/ISBT) of cervical cancer by comparing graphical optimization (GO), inverse planning simulated annealing (IPSA), and hybrid inverse planning optimization (HIPO) using dosimetric and radiobiological models.Methods:This study selected 65 patients with cervical cancer who were treated with image-guided IC/ISBT. The afterloading therapy plans for these patients were optimized using GO, IPSA, and HIPO individually, with a prescription dose high-risk clinical target volume (HRCTV) D90 of 6 Gy. The non-parametric Friedman test and the non-parametric Wilcoxon rank test were employed to analyze the differences in duration, dose-volume parameters, and radiobiology between the three types of optimized plans. Results:Inverse planning optimization (IPSA: 46.53 s; HIPO: 98.36 s) took less time than GO (135.03 s). In terms of gross target volume (GTV) dose, the high-dose irradiation V150% (53.66%) was slightly higher in the HIPO-optimized plans, while the V200% (30.29%) was higher in the GO-optimized plans. The GO-optimized plans had a higher conformity index (CI; 0.91) than other plans, showing statistically significant differences. Compared with other plans, the HIPO-optimized plans showed the lowest doses of D1 cm 3 and D2 cm 3 at bladders and rectums and non-statistically significant doses at small intestines ( P > 0.05). In terms of the equivalent uniform biologically effective dose (EUBED) for HRCTV, the HIPO-optimized plans showed a higher value (12.35 Gy) than the GO-optimized plans (12.23 Gy) and the IPSA-optimized plans (12.13 Gy). Moreover, the EUBED at bladders was the lowest (2.38 Gy) in the GO-optimized plans, the EUBED at rectums was the lowest (3.74 Gy) in the HIPO-optimized plans, and the EUBED at small intestines was non-significantly different among the three types of optimized plans ( P = 0.055). There was no significant difference in the tumor control probability (TCP) predicted using the three types of optimized plans ( P > 0.05). The normal tissue complication probabilities (NTCPs) of bladders and rectums predicted using the HIPO-optimized plans were lower than those predicted using the GO- and IPSA-optimized plans( χ2 = 12.95-38.43, P < 0.01), and the NTCP of small intestines did not show significant differences ( P > 0.05). Conclusions:Among the three types of optimization algorithms, inverse optimization takes less time than GO. GO-optimized plans are more conformal than IPSA- and HIPO-optimized plans. HIPO-optimized plans can increase the biological coverage dose of the target volume and reduce the maximum physical/biological exposure and NTCP at bladders and rectums. Therefore, HIPO is recommended preferentially as an optimization algorithm for IC/ISBT for cervical cancer.

Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has anti-inflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.

We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an extra 29-nucleotide sequence located at the nucleotide positions between 27,863 and 27,864 (referred to the complete sequence of BJ01) within an overlapped region composed of BGI-PUP5 (BGI-postulated uncharacterized protein 5) and BGI-PUP6 upstream of the N (nucleocapsid) protein. The discovery of this minor genotype, GD-Ins29, suggests a significant genetic event and differentiates it from the previously reported genotype, the dominant form among all sequenced SARS-CoV isolates. A 17-nt segment of this extra sequence is identical to a segment of the same size in two human mRNA sequences that may interfere with viral replication and transcription in the cytosol of the infected cells. It provides a new avenue for the exploration of the virus-host interaction in viral evolution, host pathogenesis, and vaccine development.
Base Sequence ; China ; Cluster Analysis ; Gene Components ; Genetic Variation ; Genome, Viral ; Genotype ; Molecular Sequence Data ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction ; SARS Virus ; genetics ; Sequence Analysis, DNA ; Severe Acute Respiratory Syndrome ; genetics