Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Ferroptosis is a unique and novel form of regulated cell death characterized by iron depend-ence and lipid peroxidation.Ferroptosis can occur in multiple organelles,and more and more studies have found that mitochondria-dependent ferroptosis plays an important role in the progression of various diseases such as gastrointestinal tumors.Mitochondria,as the core of cellular substance and energy me-tabolism,can trigger mitochondria-dependent ferroptosis by producing reactive oxygen species through structures such as electron transport chains located in the inner membrane.It can also resist ferroptosis through antioxidant systems such as dihydroorotate dehydrogenase located on the outer side of the mito-chondrial inner membrane.Therefore,by targeting the molecules related to mitochondria-dependent fer-roptosis,it is expected to achieve accurate treatment of gastrointestinal tumors.This article reviews the morphological changes of mitochondria in ferroptosis,and summarizes the specific mechanisms of mito-chondria-dependent ferroptosis,including energy metabolism,lipid metabolism,iron metabolism,and other regulatory mechanisms involved.At the same time,the effect of mitochondria-dependent ferroptosis on the biological studies of gastrointestinal tumors and its potential value in the treatment of gastrointesti-nal tumors were also illustrated.This article reviews the specific mechanism of mitochondria-dependent ferroptosis and its application in the prognostic prediction and treatment in gastrointestinal tumors,aiming to provide potential targets for the prognosis prediction and treatment of gastrointestinal tumors.

Ferroptosis is a unique and novel form of regulated cell death characterized by iron depend-ence and lipid peroxidation.Ferroptosis can occur in multiple organelles,and more and more studies have found that mitochondria-dependent ferroptosis plays an important role in the progression of various diseases such as gastrointestinal tumors.Mitochondria,as the core of cellular substance and energy me-tabolism,can trigger mitochondria-dependent ferroptosis by producing reactive oxygen species through structures such as electron transport chains located in the inner membrane.It can also resist ferroptosis through antioxidant systems such as dihydroorotate dehydrogenase located on the outer side of the mito-chondrial inner membrane.Therefore,by targeting the molecules related to mitochondria-dependent fer-roptosis,it is expected to achieve accurate treatment of gastrointestinal tumors.This article reviews the morphological changes of mitochondria in ferroptosis,and summarizes the specific mechanisms of mito-chondria-dependent ferroptosis,including energy metabolism,lipid metabolism,iron metabolism,and other regulatory mechanisms involved.At the same time,the effect of mitochondria-dependent ferroptosis on the biological studies of gastrointestinal tumors and its potential value in the treatment of gastrointesti-nal tumors were also illustrated.This article reviews the specific mechanism of mitochondria-dependent ferroptosis and its application in the prognostic prediction and treatment in gastrointestinal tumors,aiming to provide potential targets for the prognosis prediction and treatment of gastrointestinal tumors.

Antrodia cinnamomea is extensively used as a traditional medicine to prevention and treatment of liver cancer. However, its comprehensive chemical fingerprint is uncertain, and the mechanisms, especially the potential therapeutic target for anti-hepatocellular carcinoma (HCC) are still unclear. Using UPLC‒Q-TOF/MS, 139 chemical components were identified in A. cinnamomea dropping pills (ACDPs). Based on these chemical components, network pharmacology demonstrated that the targets of active components were significantly enriched in the pathways in cancer, which were closely related with cell proliferation regulation. Next, HCC data was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET were analyzed by bioinformatics, and 79 biomarkers were obtained. Furtherly, nine targets of ACDP active components were revealed, and they were significantly enriched in PI3K/AKT and cell cycle signaling pathways. The affinity between these targets and their corresponding active ingredients was predicted by molecular docking. Finally, in vivo and in vitro experiments showed that ACDPs could reduce the activity of PI3K/AKT signaling pathway and downregulate the expression of cell cycle-related proteins, contributing to the decreased growth of liver cancer. Altogether, PI3K/AKT-cell cycle appears as the significant central node in anti-liver cancer of A. Cinnamomea.

To provide guidance for quality control and variety breeding of Gastrodia elata f. glauca cultivated form in Zhaotong, nine agronomic traits of G. elata f. glauca cultivation form were measured and the traits were analyzed using multiple comparison,correlation analysis, multiple stepwise regression analysis and path analysis. The results of multiple comparison and analysis showed that the number of dot ring and the length-width ratio of tuber were no different in G. elata f. glauca cultivation form. The coefficient of variation about the single tuber fresh weigh, ring spacing and belly button diameter was about 20%. The coefficient of variation about the length of the tuber, the width of the tuber, the thickness of the tuber, the length-width ratio of tuber and the number of dot ring was near 10%. The correlation analysis results showed that the single tuber fresh weigh and the length,the width and the thickness of the tuber were extremely significant positive correlated. The results of multiple stepwise regression analysis and path analysis showed that the length, the width and the thickness of the tuber were the main factors affecting the fresh weight of single tuber,which were the best agronomic traits on high yield of G. elata f. glauca. The length of the tuber,the width of the tuber and the thickness of the tuber, which would be used as indicators of the characteristics of high yield varieties in Zhaotong. The number of dot ring and the length-width ratio of tuber, which would be selected as quality control indicators of the genuine Chinese medicinal materials in Zhaotong.

The certified reference materials (CRMs) of emodin in rhubarb and its alcohol extract, water extract were developed by using quantity transfer technology from single chemical composition to the complex systems. The CRM of emodin was used for quantity transfer, and high performance liquid chromatography (HPLC) method was used to determine the contents of emodin in different matrix composition. By establishing mathematical model and calculating the parts of uncertainty, the uncertainty values were finally gotten. CRMs of emodin in rhubarb, alcohol extract and water extract were accomplished. The content values of emodin were 0.40% ±0.03%, 1.15%±0.18%, 0.16%±0.08% (k=2,P=0.95), respectively. The established method for quantity transfer has successfully solved the technical problems that the value of active ingredient of traditional Chinese medicine can't be traced to SI units. The series of CRMs are assigned as grade primary reference materials, which are useful for quality control of the emodin content, also provide the accurate and reliable CRM, materials standard and standard methods.

Objective To study the distribution and properly of the transparent globules within Hensen cells (HC) of guinea -pig Corti organ .Methods The cochlear epithelial cells were isolated from 10 guinea pigs .The cells of cochlea were marked by Bodipy493/503 ,sudan III ,oil red O ,and osmium tetroxide .Results The transpar‐ent globules within the HCs of the guinea -pigs were green staining by Bodipy493/503 ,jacinth staining by Sudan III ,ruby red by oil red O .And they were black globules stripe as post -fixed in 1% osmium tetroxide .Conclusion The results indicate that the transparent globules within guinea -pigs HCs'lipid droplets by four methods .

Objective To elucidate the pharmacokinetic/pharmacody-namic ( PK/PD ) parameters that predict tebipenem pivoxil efficacy against Klebsiella pneumoniae in murine lung infection model. Methods The minimal inhibitory concentration ( MIC ) of tebipenem pivoxil against Klebsiella pneumoniae was determined by standard two-fold agar dilution method.Three doses of 50, 15 and 3mg? kg-1 were given to lung infection models, respectively.The bacterial burden in lung was measured 24 hours after the initiation of treatment and the concentra-tion in plasma was determined by high performance liquid chromatogra-phy ( HPLC) .Results The MIC value was 0.03 μg? mL-1 .Three doses all showed effects on murine lung infection model.Three PK/PD parameters correlated with efficacy of tebipenem pivoxil were AUC/MIC ( r =0.78 ) , Cmax/MIC ( r =0.76 ) , and T >MIC ( r =0.46 ) . Conclusion PK/PD study indicates AUC/MIC and Cmax/MIC are PK/PD parameters, well correlated with the efficacy of tebipenem pivoxil against Klebsiella pneumoniae in murine lung infection model.

OBJECTIVETo explore the grey matter volume (GMV) changes in neuromyelitis optica (NMO) patients using a voxel-based morphometry method.

METHODSWhole brain structural images were acquired in 16 NMO patients and 16 gender-and age-matched healthy controls. Comparison of GMV between the two groups was analyzed by VBM8 toolbox of statistical parametric mapping 8.

RESULTCompared with the controls, NMO patients showed decreased GMV in the frontal lobe, parietal lobe, temporal lobe, occipital lobe, limbic lobe, optic tract, caudate nucleus, thalamus, and cerebellum (all P < 0.005).

CONCLUSIONSRegional atrophy of grey matter is found in NMO patients. Voxel-based morphometry can reveal brain volume changes sensitively.

Adolescent ; Adult ; Case-Control Studies ; Female ; Gray Matter ; pathology ; Humans ; Magnetic Resonance Imaging ; Male ; Neuromyelitis Optica ; pathology ; Young Adult

OBJECTIVETo evaluate the technical feasibility, effectiveness, and safety of robot-assisted gastrectomy(RAG) with lymphadenectomy using the Da Vinci system.

METHODSA total of 9 patients in our institute from March 17 to April 24 2010 underwent RAG. Clinicopathologic characteristics and surgical outcomes were summarized.

RESULTSAll operations were performed successfully without conversion to either open or laparoscopic approach. There were 5 total gastrectomies,2 distal gastrectomies, 1 proximal gastrectomy and 1 wedge gastrectomy with D(1) or D(2) lymphadenectomy. The total operative time was 150 to 440 minutes. Total blood loss ranged from 10 to 100 ml. The ranges of harvested lymph nodes were 19-24 for D(1) patients and 28-38 for D(2) patients. There was 1 case of postoperative gastric leakage, which were managed conservatively.

CONCLUSIONSRAG with lymphadenectomy can be applied safely and effectively for patients with gastric cancer.

Adult ; Aged ; Artificial Intelligence ; Female ; Gastrectomy ; instrumentation ; methods ; Humans ; Lymph Node Excision ; instrumentation ; methods ; Male ; Middle Aged ; Robotics ; Stomach Neoplasms ; surgery ; Young Adult