[Establishment of quality evaluation criteria for out-patient medical records of cancer pain and assessment of its application effect].

Objective: To establish the quality evaluation criteria for out-patient medical records of cancer pain and evaluate the effect of its application. Methods: The evaluation criterion was established based on Delphi method for out-patient medical records of cancer pain in the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University. Firstly, the weight of each evaluation indicator was calculated by the method of Attribute Hierarchical Model in combination with technique for order preference by similarity to solution (AHM-TOPSIS), and out-patient medical records of 50 cancer pain patients (group A, 150 records) received in June 2020 were assessed comprehensively. Secondly, the relative closeness (Ci value) between the writing quality and the ideal solution was calculated, as well as the proportion of evaluation indicators which were lack of standardization. Thirdly, the corresponding countermeasures were adapted based on the results of assessment. Finally, another 50 medical records (156 records) received in October 2021 were re-evaluated by the same method, and the differences of quality of medical record and proportion of each evaluation indicator which was lack of standardization before and after the intervention were compared. Results: A specific criterion which contained integrity of materials required for the medical records, documents of the complaints and medical history of cancer pain, description of the previous medical treatment for cancer pain, regular assessment of cancer pain and its' document, quantitative assessment and its' document, comprehensive assessment and its' document, dynamic assessment and its' document, reasonable of pain medication, reasonable of the drug usage and dosage, reasonable adjustment of the drug variety or dosage, prevention of adverse reactions of analgesic drugs and its' document, evaluation and management of adverse reactions of analgesic drugs and its' document (12 indicators) was established to evaluate the out-patient medical records of cancer pain. The proportion of medical records which Ci≥0.6 was 62.0% (93/150) in group A before the intervention. It was increased to 84.6% (132/156) in group B after the intervention and the difference was statistically significant (P<0.001). Furthermore, the proportions of comprehensive assessment of cancer pain which were lack of standardization, prevention of adverse reaction, quantitative evaluation and dynamic assessment of cancer pain accounted for a higher level, which was 64.0% (96/150), 55.3% (83/150), 54.7% (93/150) and 52.7% (79/150) respectively in group A before the intervention. However, proportions of such records were decreased to 50.6% (79/156), 35.9% (56/156), 32.1% (50/156) and 39.7% (62/156) respectively in group B after the intervention and the differences were statistically significant (all P<0.05). Conclusions: A specific quality evaluation criterion is established based on Delphi method and AHM-TOPSIS for the out-patient medical records of cancer pain. The quality of medical records has been improved in a certain level after adapting comprehensive evaluation and intervention on the out-patient medical records of cancer pain.

[Safety and efficacy of dual guiding catheter kissing technique in the treatment of stent partially dislodgement in coronary artery].

Objective: To investigate the safety and efficacy of dual guiding catheter kissing technique (DCK) in the treatment of stent partly dislodgement in coronary artery. Methods: The study retrospectively involved 6 hospitalized patients with coronary artery stent partly dislodgement during PCI at The First Affiliated Hospital of Zhengzhou University from February 2016 to June 2019, DCK was used in these patients. We observe the success rate of stent retrieval, success rate of PCI, incidence of complications and major adverse cardiovascular events in 1 year follow up. Results: 6 patients were involved, of which 3 are male, ages range 49 to 68 years old, 4 patients are diagnosed with unstable angina, the other two are stable angina. All the partially disloged stents in the 6 patients were successfully removed from coronary artery. Except for 1 patient who refused coronary artery stenting again, the other 5 patients were successfully implanted coronary artery stenting. No serious complications occurred, no patients died and no major adverse cardiovascular events happened during 1 year follow up. Conclusions: DCK is safe and effective to remove partially dislodged stent in coronary artery.

[Endoplasmic reticulum stress regulates autophagy and tumor necrosis factor-α secretion of RAW264.7 cells induced by silica].

Objective: To investigate the role of endoplasmic reticulum stress (ERS) in the autophagy of RAW264.7 cells induced by SiO(2) and its effect on the secretion of tumor necrosis factor-α. Methods: RAW264.7 cells stimulated by 200 µg/ml SiO(2) were used as an vitro cell model, and different treatment times of SiO(2) were used as variables. They were divided into 0 h treatment group (blank control group) , 6 h, 12 h, 24 h, and 48 h treatment group. The formation of autophagospores was detected by acridine orange and mondane-sulfonate (MDC) staining. Application of real-time quantitative PCR (Real-time PCR) to detect autophagy related molecular Beclin1 mRNA expression and protein immunoblot (Western Blotting) detecting autophagy related proteins LC3Ⅰ, LC3Ⅱ and expression of Beclin1. Real-time PCR and Western blotting were used to detect the expression of ERS specific marker BiP. Secretion of RAW 264.7 cell transforming growth factor-ß1 (TGF-ß1) and tumor necrosis factor-α (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA) . ERS inhibitors 4-PBA intervention experiment, including blank control group, SiO(2), 1 µmol/L 4-PBA+SiO(2), 10 µmol/L 4-PBA+SiO(2), 20 µmol/L 4-PBA+SiO(2) treatment group, Western blotting testing LC3Ⅰ, LC3Ⅱ and expression of Beclin1 changes. Results: Compared with the control group, SiO(2)-induced fluorescence intensity in RAW264.7 cells was significantly increased, with statistically significant differences (P<0.05) . Compared with control group, with SiO(2) processing time prolonged, LC3Ⅰ, LC3Ⅱ Beclin1 mRNA and protein expression and protein expression increased, 6 h, 24 h, the height of the differences were statistically significant (P<0.05) ; Compared with the control group, the mRNA and protein expression level of BiP reached the peak for 6 h, and the expression level in 6 h, 12 h and 24 h groups increased significantly, and the difference was statistically significant (P<0.05) . Compared with the SiO(2) stimulation group, the LC3Ⅱand Beclin 1 protein levels of RAW264.7 cells were gradually down-regulated by increasing the dose of 4-PBA. With the increase of 4-PBA concentration, the down-regulated levels were more significant, and the difference was statistically significant (P<0.05) . Compared with the SiO(2) stimulation group, the TNF-α secretion level of RAW264.7 cells significantly decreased of 1, 10, 20 µmol/L 4-PBA+SiO(2) treatment group, and the difference was statistically significant (P<0.05) . Conclusion: ERS induced by SiO(2) is involved in the secretion of autophagy and TNF-α in RAW264.7 cells.

[Outcomes of patients treated with drug-coated balloons for de novo large coronary vessels].

Objective: To evaluate the efficacy and safety of drug-coated balloons (DCB) for de novo large coronary vessels. Methods: One hundred and two patients were retrospectively enrolled in this study, there were 104 lesions with the reference lumen diameter of target vessel more than 2.8 mm and patients were treated with DCB in de novo lesions during May 2015 and July 2017 in our center. Coronary artery angiography and quantitative coronary angiography were performed in 82 (80.4%) patients at follow up period ((8.1±1.7) months post procedure). The endpoints were late lumen loss (LLL) at follow up,and major adverse cardiac events (MACE) including cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and stent or target lesion thrombosis at 12 months post procedure. Results: Ninety-eight lesions were treated with DCB only, 6 (5.9%) bailout drug-eluting stent (DES) were used because of severe coronary dissection, 2 patients (2.0%) received revascularization driven by acute ischemic events during hospitalization. Cutting balloons and NSE balloons were used in 65.4% (68/104) and 26.0% (27/104) lesions. The lesion length was (12.57±3.58) mm and the DCB length was (19.87±4.55) mm. The late lumen loss was (0.01±0.52) mm during angiographic follow up. The TLR rate and overall MACE rate was 3.9% (4/102) and 3.9% (4/102) and there was no death,MI and target lesion thrombosis at 12 months follow up. Conclusion: DCB treatment for de novo large coronary vessels is effective and safe.

Polybrominated diphenyl ethers in mudsnails (Cipangopaludina cahayensis) and sediments from an electronic waste recycling region in South China.

Mudsnails and sediments from an electronic waste recycling region in South China were chosen to study the polybrominated diphenyl ethers (PBDEs) bioavailability of mudsnail in different ambient levels. Significant (p < 0.05) correlations of biota-sediment accumulation factor (BSAF) versus the reciprocal of PBDE concentration in sediment (1/Sed) occurred in all quantitative PBDE congeners except BDE-209, showed that the BSAFs of PBDEs in mudsnails were increased with reciprocal increasing ambient levels. The BDE-183 correlation of mudsnail versus sediment (r = 0.580) was much lower than the correlation of BDE-209 versus BDE-183 in mudsnails (r = 0.812), indicated the main source of BDE-183 in mudsnails was from the debromination of higher brominated PBDEs.

Polybrominated diphenyl ethers in leaves and soil from typical electronic waste polluted area in South China.

Polybrominated diphenyl ethers (PBDEs) in leaves and soil from typical e-waste polluted area in South China were investigated. The concentrations (ng/g dry weight) of PBDE congeners and summation operatorPBDE of five leaf samples were much lower than those in soil sample. The general patterns of summation di-BDEs to summation hepta-BDEs percentage distribution in leaf samples were similar to those of the soil sample, except the percentage of BDE209 which were lower than in soil. The percentages of summation di-BDEs to summation hepta-BDEs in soil were in the range of those in leaf samples. The results showed that the contamination of PBDEs in the leaf samples had good correlation with the soil around them.

Impaired inactivation of digestive proteases by deconjugated bilirubin: the possible mechanism for inflammatory bowel disease.

Inflammatory bowel disease refers to ulcerative colitis and Crohn's disease, two gut diseases with unknown causes. The dramatic increase in the last half century and the big difference in incidence for people with the same ethnic background but living in different areas strongly suggested that environmental factors played the dominant role for these diseases. The similarity in many aspects for these two diseases suggested a common causative factor. Here I suggest the impaired inactivation of digestive proteases by deconjugated bilirubin, as the result of the inhibition of bilirubin deconjugation enzyme, beta-glucuronidase, originated from the luminal bacteria and mucosa of the gut, to be a possible mechanism for both ulcerative colitis and Crohn's diseases. I also provide evidence to suggest that saccharin could be the causative or one of the most important risk factors for inflammatory bowel disease as for its inhibition on beta-glucuronidase in the intestine.

Retroviruses as tools to study the immune system.

Retrovirus-based vectors provide an efficient means to introduce and express genes in cells of the immune system and have become a popular tool to study immune function. They are easy to manipulate and provide stable, long-term gene expression because they integrate into the genome. Current retroviral vectors do have limitations that affect their usefulness in certain applications. However, recent advances suggest a number of ways in which these vectors might be improved to extend their utility in immunological research.

Secondary V(D)J recombination in B-1 cells.

B-1 B cells are a self-renewing population of B cells that differ from conventional B cells (B-2 cells) in that they are particularly predisposed to auto-antibody production. Although much is known about the signalling pathways that control B-1-cell growth and development, less is known about why these cells are prone to produce autoreactive antibodies. Here we show that B-1 cells, like germinal-centre B cells, can express recombinase-activating genes 1 and 2 (RAG1 and RAG2) and undergo secondary V(D)J recombination of immunoglobulin genes. In addition, B cells from autoimmune-prone NZB mice show high levels of RAG messenger RNA and recombination. We propose that secondary immunoglobulin-gene rearrangements outside organized lymphoid organs may contribute to the development of autoreactive antibodies.

OCA-B integrates B cell antigen receptor-, CD40L- and IL 4-mediated signals for the germinal center pathway of B cell development.

Many of the key decisions in lymphocyte differentiation and activation are dependent on integration of antigen receptor and co-receptor signals. Although there is significant understanding of these receptors and their signaling pathways, little is known about the molecular requirements for signal integration at the level of activation of gene expression. Here we show that in primary B cells, expression of the B-cell specific transcription coactivator OCA-B (also known as OBF-1 or Bob-1) is regulated synergistically by the B-cell antigen receptor, CD40L and interleukin signaling pathways. Consistent with the requirement for multiple T cell-dependent signals to induce OCA-B, we find that OCA-B protein is highly expressed in germinal center B cells. Accordingly, germinal center formation is blocked completely in the absence of OCA-B expression in B cells, whereas the helper functions of OCA-B-deficient T cells are indistinguishable from controls. The requirement for OCA-B expression in B cells is germinal center specific since the development of primary B cell follicles, the marginal zone and plasma cells are all intact. Thus, OCA-B is the first example of a transcriptional coactivator that is both synergistically induced by and required for integration of signals that mediate cell fate decisions.

Ku80 is required for immunoglobulin isotype switching.

Isotype switching is the DNA recombination mechanism by which antibody genes diversify immunoglobulin effector functions. In contrast to V(D)J recombination, which is mediated by RAG1, RAG2 and DNA double-stranded break (DSB) repair proteins, little is known about the mechanism of switching. We have investigated the role of DNA DSB repair in switch recombination in mice that are unable to repair DSBs due to a deficiency in Ku80 (Ku80(-/-)). B-cell development is arrested at the pro-B cell stage in Ku80(-/-) mice because of abnormalities in V(D)J recombination, and there are no mature B cells. To reconstitute the B-cell compartment in Ku80(-/-) mice, pre-rearranged VB1-8 DJH2 (mu i) and V3-83JK2 (kappa i) genes were introduced into the Ku80(-/-) background (Ku80(-/-)mu i/+kappa i/+). Ku80(-/-)mu i/+ kappai/+ mice develop mature mIgM+ B cells that respond normally to lipopolysaccharide (LPS) or LPS plus interleukin-4 (IL-4) by producing specific germline Ig constant region transcripts and by forming switch region-specific DSBs. However, Ku80(-/-)mu i/+kappa i/+ B cells are unable to produce immunoglobulins of secondary isotypes, and fail to complete switch recombination. Thus, Ku80 is essential for switch recombination in vivo, suggesting a significant overlap between the molecular machinery that mediates DNA DSB repair, V(D)J recombination and isotype switching.

V(D)J recombination in mature B cells: a mechanism for altering antibody responses.

The clonal selection theory states that B lymphocytes producing high-affinity immunoglobulins are selected from a pool of cells undergoing antibody gene mutation. Somatic hypermutation is a well-documented mechanism for achieving diversification of immune responses in mature B cells. Antibody genes were also found to be modified in such cells in germinal centers by recombination of the variable (V), diversity (D), and joining (J) segments. The ability to alter immunoglobulin expression by V(D)J recombination in the selective environment of the germinal center may be an additional mechanism for inactivation or diversification of immune responses.

Cloning and sequencing of the pancreatic islet neogenesis associated protein (INGAP) gene and its expression in islet neogenesis in hamsters.

Induction of islet neogenesis by cellophane wrapping (CW) reverses streptozotocin-induced (STZ) diabetes. Administration of Ilotropin, a protein extract isolated from CW pancreata, causes recapitulation of normal islet ontogeny and reverses STZ diabetes, reducing mortality by 50%. We investigated the hypothesis that a novel gene encoding a constituent of Ilotropin was expressed in the hamster pancreas undergoing islet neogenesis. Islet neogenesis associated protein (INGAP) is a product of a novel gene expressed in regenerating hamster pancreas. Northern blot analysis showed a strong single transcript of 850 bp at 1 and 2 d after CW that disappeared by the 6th day and was absent from untreated control pancreata. INGAP gene is expressed in acinar cells, but not in islets. Western blot analysis demonstrated the presence of INGAP in Ilotropin but not in extracts from control pancreata. A synthetic pentadecapeptide, corresponding to a region unique to INGAP, stimulated a 2.4-fold increase in [3H]thymidine incorporation into hamster duct epithelium in primary culture and a rat pancreatic duct cell line but had no effect on a hamster insulinoma tumor cell line. A portion of human INGAP gene was cloned and appears to be highly homologous to the hamster gene. This data suggests that the INGAP gene is a novel pancreatic gene expressed during islet neogenesis whose protein product is a constituent of Ilotropin and is capable of initiating duct cell proliferation, a prerequisite for islet neogenesis.

The B-cell-specific transcription coactivator OCA-B/OBF-1/Bob-1 is essential for normal production of immunoglobulin isotypes.

OCA-B was initially identified as a B-cell-restricted coactivator that functions with octamer binding transcription factors (Oct-1 and Oct-2) to mediate efficient cell type-specific transcription of immunoglobulin promoters in vitro. Subsequent cloning studies led to identification of the coactivator as a single polypeptide, designated either as OCA-B (ref. 3), OBF-1 (ref. 4) or Bob-1 (ref. 5). OCA-B itself does not bind to DNA directly, but interacts with either Oct-1 or Oct-2 to potentiate transcriptional activation. To determine the biological role of OCA-B, we generated OCA-B-deficient mice by gene targeting. Mice lacking OCA-B undergo normal antigen-independent, B-cell differentiation, including appropriate expression of both immunoglobulin genes and other early B-cell-restricted genes. However, antigen-dependent maturation of B cells is greatly affected. The proliferative response to surface IgM crosslinking is impaired, and there is a severe deficiency in the production of secondary immunoglobulin isotypes including IgG1, IgG2a, IgG2b, IgG3, IgA and IgE in OCA-B-deficient B cells. This defect is not due to a failure of the isotype switching process, but rather to reduced levels of transcription from normally switched immunoglobulin heavy-chain loci. In accord with the defective isotype production, germinal centre formation is absent in these mutant mice.

Identification of differentially expressed genes induced in pancreatic islet neogenesis.

Cellophane wrapping of the hamster pancreas induces islet neogenesis. We have used the mRNA differential display technique to select for genes expressed during islet neogenesis but not in control pancreata. Ten candidate clones have been identified. Upon sequencing, 6 clones showed a high degree of homology to known genes, 1 showed some, and 3 showed no homology to genes of known sequence. Thus, mRNA differential display is a useful technique to identify genes induced during islet neogenesis, and in combination with screening hamster pancreatic cDNA libraries for full length clones, will enhance the likelihood of capturing the participants in this process.

Transformation by homeobox genes can be mediated by selective transcriptional repression.

Altered transcription is a recurrent theme in the field of cancer biology. But despite the central role of transcription in transformation, little is known about the mechanism by which dominant nuclear oncogenes induce malignancies. Homeobox family proteins are prominent examples of transcriptional regulators which control development and can function as oncogenes. Here we explore the molecular basis for transformation by this class of regulators using Oct-2 and Oct-1. We show that the DNA binding POU domains of these proteins are selective and sequence-specific transcriptional repressors that produce malignant lymphomas when they are expressed in T cells of transgenic mice. Mutagenesis experiments identified a specific set of promoters, those containing octamer regulatory elements, as the targets for transformation by selective inhibition of gene expression.

Immediate early transcription activation by salicylic acid via the cauliflower mosaic virus as-1 element.

Transgenic tobacco plants carrying a number of regulatory sequences derived from the cauliflower mosaic virus 35S promoter were tested for their response to treatment with salicylic acid (SA), an endogenous signal involved in plant defense responses. beta-Glucuronidase (GUS) gene fusions with the full-length (-343 to +8) 35S promoter or the -90 truncation were found to be induced by SA. Time course experiments revealed that, in the continuous presence of SA, the -90 promoter construct (-90 35S-GUS) displayed rapid and transient induction kinetics, with maximum RNA levels at 1 to 4 hr, which declined to low levels by 24 hr. Induction was still apparent in the presence of the protein synthesis inhibitor cycloheximide (CHX). Moreover, mRNA levels continued to accumulate over 24 hr rather than to decline. By contrast, mRNA from the endogenous pathogenesis-related protein-1a (PR-1a) gene began to accumulate at later times during SA treatment and steadily increased through 24 hr; transcription of this gene was almost completely blocked by the presence of CHX. Further dissection of the region from -90 and -46 of the 35S promoter revealed that the SA-responsive element corresponds to the previously characterized activation sequence-1 (as-1). These results represent a definitive analysis of immediate early responses to SA, relative to the late induction of PR genes, and potentially elucidate the early events of SA signal transduction during the plant defense response.

[Changes of cellular hydroxyl proline and some other parameters of rats in early bronchoalveolar lavage treated with quartz dust].

The changes of cellular hydroxyl proline (Hyp) and some other parameters in bronchoalveolar lavage (BAL) induced by different doses of quartz dust (5, 10, 20, or 40mg/per rat) were studied. Quartz dust was administered intratracheally and the rats were killed two weeks after quartz administration. The results showed that the differential count of polymorphonuclear leukocytes (PMN) in BAL, the concentrations of Hyp and total lipids in BAL cells, and the levels of total lipids, total protein, lactic dehydrogenase (LDH) and ceruloplasmin in BAL supernatant all changed significantly in quartz treated groups compared with the control group. Further investigation revealed that the cellular Hyp correlated best with total lung collagen (r = 0.834). This indicated that Hyp might be a specific and important parameter reflecting early increase of total lung collagen after quartz dust administration.

Morphometric measurement of collagen in liver tissue with posthepatitis liver cirrhosis portal hypertension.

A correct estimation of the collagen content in cirrhosis liver tissue and analysis of its relation to the degree of liver function injury are important to the clinician in the establishment of the diagnosis in the liver diseases. The author has performed the morphometric measurement of collagen with liver tissue pathological section by using TJTY-300 image analysis system. It was found that the cirrhotic liver tissue's collagen area and collagen average grey degree were notably higher than those in normal men (P < 0.05), average optical density was markedly lower than that in normal men (P < 0.05), integral optical density had no significant difference (P > 0.05) between patients and normal controls, but the integral optical density in cirrhotic liver was 1.21 times that of normal men. It suggests that the collagen content in cirrhotic liver tissue increased obviously, the average density of the increased collagen was lower than that in the normal liver tissue and the density of increased collagen was not homogeneous. Comparison between normal controls and patients with different Child-Pugh liver function grades in liver tissue collagen parameters revealed that the cirrhotic liver's collagen content can, to different degree, directly reflect the function status of cirrhotic liver.