Objective To explore the best procurement technology for cadaveric donor nephrectomy. Methods Clinical data of 1 439 donors nephrectomy in the past 24 years were retrospected.Bilateral nephrectomy,en bloc removal of both kidneys and en bloc removal with in situ cooling both kidneys were adopted in different periods of time.Operation time(OT),hot ischemia time(HIT),cold ischemia time(CIT),total ischemia time(TIT), renal graft beginning to produce urine time after revascularization(UT),renal function recovery time(RRT), damage rate(DR),quantity of preservation solution(PS), rate of acute tubular necrosis(ATN),primary non function(PNF) and poor perfusion of donor kidney(PPK) were observed and comparad among the 3 techniques. Results 216 cases were accomplished by bilateral nephrectomy and 432 kidneys were procured.1 134 cases were accomplished by en bloc removal and 2 264 kidneys were procured(4 cases had only one kidney each).Eighty nine cases were accomplished by en bloc removal with in situ cooling and 178 kidneys were procured. HIT of these three techniques (bilateral nephrectomy,en bloc removal and en bloc removal with in situ cooling) were 8.22?3.01min?5.35?1.88min?1.89?0.92min ( P 0.05).UT were ( 28.24 ?10.65)min,(22.72?8.35)min,(9.26? 10.95 )min.RRT were (9.98?6.84)d,( 7.59 ?6.35)d,(4.91? 7.68 )d.ATN were 15.40%,7.31%,3.98%( P

Objective To analyze the clinical manifestations,diagnosis,treatment and prognosis of patients with splenic abscess.Method The clinical data,including baseline clinical data,clinical features,past history,pathogen culture result,treatment and the prognosis were retrospectively analyzed in the patients with the discharge diagnosis splenic abscess from January 1991 to March 2012 in Peking Union Medical College Hospital.Results The media time from onset to Peking Union Medical College Hospital of the 19 patients were 29 days.Among them,9 patients were cured,8 were improved and 2 died.Risk factors,such as tumor burden,diabetes,and using immunosuppressive agents etc,can be found in most patients with splenic abscess.All the 19 patients had splenic image changes and non-specific clinical features.The most common three clinical symptoms were fever(18 cases),chills (12 cases) and shivering (11 cases).The most common three signs were abdominal tenderness (9 cases),left upper quadrant sensitive to percussion (7 cases) and splenomegaly (4 cases).The most common etiological culture results were gram negative bacilli (9 cases),gram positive coccus (8 cases),and fungi (4 cases).Conclusions Clinical features are non-specific in splenic abscess patients.Related exam such as ultrasound should be performed on patients with splenic abscess risk factors to avoid misdiagnosis.Empiric antibiotic administration should begin right after the diagnosis based on the image.Pathogen culture should be timely conducted after pus collection.Individual therapeutical protocol should be chosen according to patient's condition.

Objective:To explore the relationship between perceived stigma and self-transcendence meaning of life among male college students who have sex with men with HIV,and the role of fear of negation evaluation,seeking for meaning,perspective change in it.Methods:A total of 474 male college students who had sex with men with HIV were selected and tested with the simplified Berger HIV Stigma Scale(BHSS),Fear of Negative Evalua-tion Rating Scale(FNE),Chinese Meaning in Life Questionnaire(C-MLQ),Meaning-focused Coping Questionnaire(MFCQ),and Self-transcendence Meaning of Life Scale(SMLS).Results:The BHSS total scores were negatively correlated with the SMLS total scores(r=0.69,P＜0.001).The FNE scores and the seeking for meaning scores were mediating variables between the BHSS total scores and the SMLS total scores,with estimated effects of-0.13 and-0.11,respectively.The FNE score and seeking for meaning score played a chain mediating role in the total scores of BHSS and SMLS,with estimated effects of-0.16,the perspective change score played a moderating role in the score of the seeking for meaning and the SMLS total score(β=0.07,P＜0.05).Conclusion:Fear of negation evaluation and seeking for meaning play a mediating role between perceived stigma and self-transcendence meaning of life,as well as the moderating effect of perspective change between the search for meaning and self-transcendence meaning of life.

Objective:To detect gene mutations in a pedigree with dominant dystrophic epidermolysis bullosa (DDEB) .Methods:A 20-year-old male proband presented with repeated blisters, ulceration, pigmentation, scars on the limbs, and deformation of the nails/toenails after birth. There were 5 patients in the 3-generation family, and they all presented with typical skin lesions. Peripheral blood samples were obtained from 14 members of the pedigree (including the 5 patients) and 100 unrelated healthy controls. Whole-exome sequencing was performed in the proband to identify relevant mutation sites, which were then confirmed in the family by Sanger sequencing.Results:Genetic testing indicated that the proband and the other 4 patients all carried a missense mutation (c.7885G>A) in exon 107 of the COL7A1 gene, resulting in the substitution of glycine by arginine at amino acid position 2629 (p.G2629R). The mutation was identified neither in the 9 healthy relatives nor in the 100 unrelated healthy controls. The mutation co-segregated with DDEB in the family, and was not included in databases such as Pubmed, HGMD or ClinVar, suggesting it was a novel missense mutation. The amino acid encoded by this mutation may alter the structure of type Ⅶ collagen, thereby affecting its function.Conclusion:A novel missense mutation was identified in exon 107 of the COL7A1 gene in the family with DDEB, expanding the spectrum of mutations in the COL7A1 gene.

OBJECTIVE: To study the changes in mRNA and long non-coding RNA (lncRNA) expression profiles in a mouse model of bleomycin-induced lung fibrosis and identify lung fibrosis-related mRNA for coding-noncoding coexpression (CNC) bioinformatics analysis of the differential lncRNAs. METHODS: Lung fibrosis was induced by intratracheal injection of bleomycin in 10 C57BL/6 mice and another 10 mice with intratracheal injection of saline served as the control group. Lung tissues were harvested from the mice at 14 days after the injections and lung fibrosis was assessed using Masson and HE staining. LncRNA chip technology was used to screen the differentially expressed mRNAs and lncRNAs in mice with lung fibrosis, and GO and KEGG pathway analyses of the differential mRNAs were performed using NCBI database and UCSC database to identify possible fibrosis-related mRNAs, which were validated by qRT-PCR to construct a coding and non-coding co- expression network with the differential lncRNAs. RESULTS: Compared with the control mice, the mice with intratracheal injection of bleomycin showed obvious lung fibrosis. The results of gene chip analysis showed that 127 mRNAs were upregulated and 184 mRNAs were down-regulated in the model group as compared with the control group. GO and pathway analysis suggested that the differentially expressed genes participated mainly in immune response, cell differentiation, and cytoskeletons; the involved signal pathways were associated mainly with cytokine and cytokine receptor interaction and chemokine signal transduction. Bioinformatics analysis identified a significant coexpression network between the fibrosisrelated mRNA and the differentially expressed lncRNA. CONCLUSIONS In mice with lung fibrosis, the differential expressions of fibrosis-related mRNAs in the lung tissues are closely correlated with the co- expressions of a large number of differential lncRNAs, which points to a new direction for investigation of the pathogenesis of pulmonary fibrosis.
Animals ; Bleomycin/toxicity* ; Gene Expression Profiling ; Gene Regulatory Networks ; Mice ; Mice, Inbred C57BL ; Pulmonary Fibrosis/genetics* ; RNA, Long Noncoding/genetics* ; RNA, Messenger/genetics*

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*