Objective: To identify biomolecular markers closely related to the occurrence of kidney renal clear cell carcinoma (KIRC) and verify their expression levels in clinical samples. Methods: Stage Ⅰ KIRC mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA).Principal component analysis (PCA) was used for dimensionality reduction to screen differentially expressed genes (DEGs)，which then underwent GO and KEGG analyses.Weighted gene co-expression network analysis (WGCNA) was used to screen genes significantly related to KIRC，and a protein-protein interaction (PPI) network was constructed to screen hub genes.The diagnostic value of hub genes was evaluated with receiver operating characteristic (ROC) curve，and their prognostic value was analyzed using survival curve plots.The correlation between the mRNA expressions of hub genes and the pathological stages of KIRC was analyzed.Clinical samples of 20 patients with stage Ⅰ KIRC treated in our hospital were included，and the expressions of the hub genes in cancerous and adjacent tissues were detected with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR)，Western blotting，and enzyme-linked immunosorbent assay (ELISA). Results: A total of 8223 DEGs were screened out，including 4092 up-regulated ones and 4131 down-regulated ones.GO analysis showed that DEGs were related to bioadhesion，plasma membrane composition，and transporter activity.KEGG analysis showed that DEGs were related to pathways such as cell adhesion molecules，cytokine-cytokine receptor interactions，and interactions between viral proteins and cytokines and cytokine receptors.WGCNA analysis obtained 171 genes that were significantly related to stage Ⅰ KIRC.The hub gene，lymphocyte cytosolic protein 2 (LCP2)，screened out by the PPI network，was significantly related to stage Ⅰ KIRC.The area under the ROC curve was 0.96.The expression level was negatively correlated with the overall survival rate of patients.The expression of LCP2 was related to the stage and lymph node metastasis.Clinical verification showed that the mRNA and protein relative expressions of LCP2 in KIRC tissues were significantly higher than those in adjacent tissues (P<0.000 1). Conclusion: LCP2 is significantly up-regulated in stage Ⅰ KIRC tissues and can be used as a potential biomarker for the early diagnosis and treatment of KIRC.

Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr²⁺. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABA_A receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions.
Parvalbumins/metabolism* ; Corpus Striatum/metabolism* ; Interneurons/physiology* ; Neurons/metabolism* ; Neostriatum

In adult orbital diseases, thyroid associated ophthalmopathy (TAO) is of very high incidence rate, and it can seriously affect patients' appearance, eyesight and binocular visual function and so on, and significantly reduce the patients' quality of life.In addition to the common manifestations such as eyelid retraction, exophthalmos and strabismus, some TAO patients may suffer from obviously increased ocular pressure and even visual field damage, which are often ignored or missed in diagnosis and should be paid more attention to.The pathogenesis of elevated intraocular pressure in TAO is mainly related to the elevated episcleral venous pressure and the extraocular muscles.Because the elevated intraocular pressure resulted from TAO is secondary and its pathogenesis is complex, personalized treatment different from primary glaucoma therapy is needed.In this article, the epidemiology, pathogenesis and therapy of elevated intraocular pressure in TAO including medication, surgery, and radiotherapy were reviewed to provide reference for the clinical diagnosis and treatment for TAO.

Objective:Establishment of a new model of human primary colon cancer transplantation tumor in normal immune mice and to provide a reliable experimental animal model for studying the pathogenesis of colon cancer under normal immunity.Methods:Human colon cancer cells come from colon cancer patients who underwent surgery in the Affiliated Hospital of Jining Medical College in 2017. The mice in the cell control group were inoculated with phosphate buffered solution (PBS) containing colon cancer cells, the microcarrier control group was inoculated with PBS containing microcarrier 6, and the cell-microcarrier complex group was inoculated with the PBS containing colon cancer cell-microcarrier complex. The cells of each group were inoculated under the skin of the right axilla of mice by subcutaneous injection, and the time, size, tumor formation rate and pathological changes under microscope were recorded. The transplanted tumor tissue was immunohistochemically stained with the EnVisiion two-step method, and the tumor formation rate of the transplanted tumor was judged according to the proportion of positive cells in the visual field. The polymerase chain reaction (PCR) method was used to detect the expression of human-specific Alu sequence in mice tumor tissue.Results:After inoculation with tumor cells, the mice in the cell control group and the microcarrier control group did not die and did not form tumors; the mice in the cell-microcarrier complex group had palpable subcutaneous tumors in the right axillary subcutaneously on the 5th to 7th days after inoculation, and tumor formation rate is 67% (10/15), and the tumor volume can reach about 500 mm 3 2 to 3 weeks after vaccination. The immunohistochemistry results showed that CK20, CDX-2 and carcinoembryonic antigen were all positively expressed. The PCR results showed that the expression of human-specific Alu sequence can be detected in the transplanted tumor tissue of tumor-bearing mice. Conclusion:Human primary colon cancer cells used microcarrier 6 as a carrier to form tumors in normal immunized mice, and successfully established a new model of human colon cancer transplantation tumor in normal immune mice.

Objective:Establishment of a new model of human primary colon cancer transplantation tumor in normal immune mice and to provide a reliable experimental animal model for studying the pathogenesis of colon cancer under normal immunity.Methods:Human colon cancer cells come from colon cancer patients who underwent surgery in the Affiliated Hospital of Jining Medical College in 2017. The mice in the cell control group were inoculated with phosphate buffered solution (PBS) containing colon cancer cells, the microcarrier control group was inoculated with PBS containing microcarrier 6, and the cell-microcarrier complex group was inoculated with the PBS containing colon cancer cell-microcarrier complex. The cells of each group were inoculated under the skin of the right axilla of mice by subcutaneous injection, and the time, size, tumor formation rate and pathological changes under microscope were recorded. The transplanted tumor tissue was immunohistochemically stained with the EnVisiion two-step method, and the tumor formation rate of the transplanted tumor was judged according to the proportion of positive cells in the visual field. The polymerase chain reaction (PCR) method was used to detect the expression of human-specific Alu sequence in mice tumor tissue.Results:After inoculation with tumor cells, the mice in the cell control group and the microcarrier control group did not die and did not form tumors; the mice in the cell-microcarrier complex group had palpable subcutaneous tumors in the right axillary subcutaneously on the 5th to 7th days after inoculation, and tumor formation rate is 67% (10/15), and the tumor volume can reach about 500 mm 3 2 to 3 weeks after vaccination. The immunohistochemistry results showed that CK20, CDX-2 and carcinoembryonic antigen were all positively expressed. The PCR results showed that the expression of human-specific Alu sequence can be detected in the transplanted tumor tissue of tumor-bearing mice. Conclusion:Human primary colon cancer cells used microcarrier 6 as a carrier to form tumors in normal immunized mice, and successfully established a new model of human colon cancer transplantation tumor in normal immune mice.

Serine protease inhibitor (serpin) is a kind of serine protease activity regulator,which including nine subfamilies (SERPIN A ～ I).SERPINE (Serpin Peptidase Inhibitor,Clade E) can regulate many important life processes.In this paper,the physical and chemical properties,mechanisms and regulatory factors of SERPINE1 and SERPINE2 in the two important members of SERPINE family are introduced,and the research progress of SERPINE family in the fibrosis related diseases is described.

Background The malignant degree of the diffuse large B-cell lymphoma (DLBCL) is high.Radiation therapy is sensitive,but the therapeutic schedule can not be unified,reasonable and effective therapeutic schedule is important in clinic treatment of the DLBCL.Objective This study was to access the effect of X-ray on the cell cycle and cell apoptosis of the DLBCL.Methods DLBCL cell line was cultured and the cell suspension was inoculated to 12-well cultured plate.The cells exposed to X-ray for 6,12,24,48 hours with the irradiation doses of 2,4,6,8 Gy respectively.The cell proportions of different cycles were assayed by flow cytometer,and cell apoptosis index was evaluated and calculated.Non-irradiation cells served as controls.Results The cells grew well with a good cell vitality and round-like shape,and the growth was stable in generation 2 or 3.With the increase of X-ray doses and the lapse of irradiation time,the cell proportions in G0-G1 phase gradually reduced (Fdose =45.58,P=0.00; Ftime =43.11,P=0.00).However,cell proportions in G2-M phase were gradually increased as the increase of X-ray doses and lapse of irradiation time (Fdose =40.77,P =0.00 ; Ftime =91.91,P =0.00).In addition,the apoptotic proportion of the cells was significantly elevated with the increase of X-ray dose and irradiation time (Fdose =87.36,P =0.00; Ftime =37.31,P =0.00).Conclusions X-ray irradiation retards DLBCL in the G2-M phase and causes cell apoptosis in dose-and time-dependent manner.

Objective To summarize the diagnosis and treatment strategy of the retroperitoneal fibrosis(RPF)associated with hydronephrosis.Methods The clinical data of 26 RPF cases treated from Jan.2005 to Mar.2012 were analyzed retrospectively.Early symptoms mainly included lumbar,flank,abdominal pain,nausea and vomit.Retroperitoneal mass was found in 12(46.2％)cases by ultrasonography,while in 23(88.5％)cases by CT.Results Ureterolysis with intra-peritoneal transposition was underwent in 10 cases who were followed up for 6-25 months,and no relapse was found.Ureterocystostomy was underwent in 1 cases for difficulty in ureterolysis who was followed up for 45 months,and no relapse was found.D-J stent inter-ureter drainage was performed in 15 cases,all of whom had replaced the D-J stent discontinuously except that 2 cases had ceased replacement successfully,and all of the obstruction were relieved during the follow-up period for 16-84 months post-operatively.Conclusions Retroperitoneal mass can be found by CT of abdomen effectively.The therapeutics should depend on the pathological condition of the retroperitoneal mass.Obstruction can be relieved effectively by both ureterolysis with intraperitoneal transposition and D-J stent inter-ureter drainage and replacement.The complication occurred in the replacement of D-J can be relieved or eliminated by all kinds of measures.The unimpaired kidney drainage should be paid attention in the follow-up.

Under natural environments, plants and algae have evolved various photosynthetic acclimation mechanisms in response to the constantly changing light conditions. The state transition and long-term response processes in photosynthetic acclimation involve remodeling and composition alteration of thylakoid membrane. A chloroplast protein kinase named Stt7/STN7 has been found to have pivotal roles in both state transition and long-term response. Here we report the crystal structures of the kinase domain of a putative Stt7/STN7 homolog from Micromonas sp. RCC299 (MsStt7d) in the apo form and in complex with various nucleotide substrates. MsStt7d adopts a canonical protein kinase fold and contains all the essential residues at the active site. A novel hairpin motif, found to be a conserved feature of the Stt7/STN7 family and indispensable for the kinase stability, interacts with the activation loop and fixes it in an active conformation. We have also demonstrated that MsStt7d is a dualspecifi city kinase that phosphorylates both Thr and Tyr residues. Moreover, preliminary in vitro data suggest that it might be capable of phosphorylating a consensus N-terminal pentapeptide of light-harvesting proteins Micromonas Lhcp4 and Arabidopsis Lhcb1 directly. The potential peptide/protein substrate binding site is predicted based on the location of a pseudo-substrate contributed by the adjacent molecule within the crystallographic dimer. The structural and biochemical data presented here provide a framework for an improved understanding on the role of Stt7/STN7 in photosynthetic acclimation.
Amino Acid Sequence ; Amino Acid Substitution ; Arabidopsis ; metabolism ; Arabidopsis Proteins ; chemistry ; genetics ; metabolism ; Binding Sites ; Catalytic Domain ; Chlorophyta ; enzymology ; Crystallography, X-Ray ; Cyclin-Dependent Kinase 2 ; chemistry ; metabolism ; Molecular Sequence Data ; Phosphorylation ; Protein Structure, Secondary ; Protein-Serine-Threonine Kinases ; chemistry ; genetics ; metabolism ; Sequence Alignment ; Substrate Specificity

Objective To investigate the clinical feature,diagnosis,treatment and prognosis of endometriosis of the bladder.Methods A retrospective study was conducted to review the clinical data of 10 patients with bladder endometriosis.Patient's age ranged from 30 to 48 years (with mean age of 38 years).Eight cases were admitted to hospital with urinary tract irritating symptoms during the menstrual period and 6 cases with hematuria; 2 patients without any symptoms were found through examination.The course of disease was 1-36 months (with mean of18 months).Ultrasound shows with low echo,single,wide base and no significant blood flow mass whose boundaries are less clear within the bladder wall.CT reveals soft-mass protruding into the bladder.Results Eight of the 10 patients were undergone partial cystectomy.And 2 cases was treated with transurethral resection.All cases were pathologically confirmed to be bladder endometriosis.Recurrence and ectopic lesion had not be found during follow-up period from 10 to 72 months (with mean of 30 ± 5.6 mon).Conclusions Endometriosis is a common disease in females in their reproductive years,but thebladder endometriosis is rare.The initial diagnosis needs to be made combining with imaging studies.It is confirmed by cystoscopy and pathological biopsy.Surgery is the option for the treatment of bladder endometriosis.