[Research progress of diagnosis in neuropathic corneal pain].

The cornea is the most innervated tissue in the human body. Neuropathic pain occurring in the cornea has gradually attracted the attention of ophthalmologists. However, the definition and pathogenesis of neuropathic corneal pain (NCP) have not been clearly defined, making the diagnosis and treatment of the disease extremely challenging. In recent years, with the application of ocular surface pain assessment scales, in vivo confocal microscopy and functional magnetic resonance imaging in the clinical assessment of NCP, the diagnostic methods of NCP have been enriched. This paper reviewed the research progress of diagnostic methods of NCP, with a view to improving the ophthalmologists' understanding of NCP and promoting the application of these technologies in the diagnosis of NCP.

[Correlation of inflammatory cells and corneal nerve damage in fungal keratitis on in vivo confocal microscopy].

Objective: To investigate the relationship between inflammatory cell infiltration and nerve damage in patients with fungal keratitis at different degrees of severity. Methods: Retrospective study. A total of 44 consecutive patients (44 eyes) with fungal keratitis in Beijing Tongren Hospital Affiliated to Capital Medical University from January 2017 to December 2019 were selected as the patient group, including 30 males and 14 females, with an age of (58.3±11.5) years old. Twenty healthy people (20 eyes) were included as control group. Slit-lamp microscopy was performed to observe the corneal ulcer. According to the diameter of corneal ulcer, patients were divided into mild, moderate and severe groups. With in vivo confocal microscopic ,the images were obtained from the epithelial layer to the endothelial layer in the central cornea and superior, inferior, nasal and temporal peripheral cornea. Parameters of the maximum density of fungal hyphae, the maximum depth of hyphal infiltration, the density, area and length of dendritic cells (DCs), the nerve density, and the number and curvature of nerve trunks were collected. The Kruskal-Wallis test, Wilcoxon test, and Spearman correlation analysis were used for analyses. Results: On confocal microscopy, many uniform, highly reflective, segment-like structures in parallel or staggered rows were detected in the cornea, with a certain degree of physiological curvature and branching. Quantitative analysis of hyphal density found that the median rating of hyphal density was 2.6 (2.0, 3.0), mainly with medium to large amounts of hyphae. Most hyphae were 100-150 µm in depth (18 cases, 40.9%), and the maximum depth of hyphae in 95.5% (42 cases) of patients was within 300 µm. The hyphal invasion depth in the mild group was 89.4 (50.5, 106.8) µm, in the moderate group was 133 (122, 203) µm, and in the severe group was 135 (74, 151) µm. As the severity of the disease increased, the depth of hyphal invasion increased (F=4.248, P=0.001). Compared with the control group, the DC density [166 (81.3, 212.5) vs. 24.0 (20.8, 32.3) cells/µm2], area [441.3 (291.9, 529.5) vs. 63.7 (47.7, 70.3) µm2] and length [68.3 (39.4, 91.0) vs. 9.2 (7.0, 11.3) µm] increased in patients (W=493.5, 500.0, 500.0; P<0.01). The nerve density [5 398.3 (3 202.7, 6 828.3) vs. 19 171.8 (17 558.8, 21 550.4) µm/mm2; t=-14.448, P<0.01] and the length [692.7 (402.0, 925.1) vs.2 138.4 (1 940.4, 2 597.2) µm; t=-11.930, P<0.01] and number [2.9 (2.0,3.0) vs. 6.0 (5.5,7.0); t=-8.282, P<0.01] of nerve trunks in patients decreased. There were strong negative correlations between the nerve density, the number of nerve trunks, and the DC density (r=-0.555, -0.466; P<0.01). Conclusions: The depth of fungal hypha invasion in patients with fungal keratitis is mainly concentrated in the epithelial layer and superficial stroma layer. The density of mature dendritic cells in the lesion area was negatively correlated with the density and number of subbasal nerves. The density of subbasal nerves decreased as the increase of the severity of the lesion. (Chin J Ophthalmol, 2021, 57: 580-588).

LPAR5 stimulates the malignant progression of non-small-cell lung carcinoma by upregulating MLLT11.

OBJECTIVE: This study aims to explore the diagnostic and prognostic values of Lysophosphatidic acid receptor 5 (LPAR5) in non-small-cell lung cancer (NSCLC) and its regulatory effects on biological functions of NSCLC cells. PATIENTS AND METHODS: NSCLC and adjacent non-tumoral tissues were collected for analyzing differential levels of LPAR5 by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Clinical information of recruited NSCLC patients was collected for assessing the diagnostic and prognostic values of LPAR5. In vitro regulation of LPAR5 on proliferative and migratory potentials of H1299 and SPC-A1 cells was examined by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. In addition, in vivo regulation of LPAR5 on the growth rate of NSCLC in nude mice was detected by tumorigenicity assay. The interaction between LPAR5 and its downstream target MLLT11 was determined by rescue experiments. RESULTS: LPAR5 was upregulated in NSCLC tissues than adjacent non-tumoral ones. High level of LPAR5 predicted higher rates of lymphatic metastasis and distant metastasis, as well as worse overall survival and progression-free survival in NSCLC. Knockdown of LPAR5 not only attenuated in vitro proliferative and migratory abilities in H1299 and SPC-A1 cells, but also slowed down in vivo growth of NSCLC in nude mice. MLLT11 was upregulated in NSCLC tissues, and displayed a positive correlation to LPAR5. Overexpression of MLLT11 was able to reverse the attenuated in vitro proliferative and migratory abilities, and the suppressed in vivo growth of NSCLC because of LPAR5 knockdown. CONCLUSIONS: LPAR5 stimulates proliferative and migratory potentials in NSCLC by positively regulating MLLT11, which can be served as an effective diagnostic marker for early stage NSCLC.

[Short-term outcomes of lung transplant recipients using organs from brain death donors].

Objective: To assess short-term outcomes after lung transplantation with organs procured following brain death. Methods: Between April 2015 and July 2016, all 17 recipients after lung transplantation using organs from brain death donors (DBD) at Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine were enrolled in this study. All patients were male, aging (60±7) years, including 11 chronic obstructive pulmonary disease, 5 idiopathic pulmonary fibrosis, 1 silicosis. Seventeen donors were 16 males and 1 female, with 10 traumatic brain injury, 5 cerebrovascular accident and 2 sudden cardiac death. Of 17 recipients receiving DBD lung transplant, 16 were single lung transplant. Data were collected including intubation duration of mechanical ventilation, hospital length of stay, incidence of pulmonary infection bronchus anastomosis complications, primary graft dysfunction (PGD), and acute rejection, bronchiolitis obliterans syndrome (BOS) as well as mortality of 90-day after lung transplantation. Results: Median duration of intubation were 2 (2) days (M(QR)) in recipients after lung transplantation. The incidence of pulmonary infection and bronchus anastomosis complications were 15/17 and 5/17, respectively. Median length of stay in hospital were 56 (19) days. The ratio of readmission 1 month after discharge were 10/17. Mortality of 90-day post-transplant were 2/17. The incidence of PGD and BOS were 1/17 and 2/17, respectively. Conclusion: Recipients with DBD lung transplantation have an acceptable survival during short-term follow-up, but with higher incidences of complications related to infection post-transplantation.

Methylprednisolone combined with low-dose indomethacin treating acute fibrinous and organizing pneumonia after a surgical resection of rectal adenocarcinoma: a case report and literature review.

OBJECTIVE: Acute Fibrinous and Organizing Pneumonia (AFOP) is a new pathologic pattern of acute lung injury characterized by the presence of intra-alveolar fibrin in the form of fibrin "balls" in a patchy distribution. CASE REPORT: A 65-years-old female after a surgical resection of rectal adenocarcinoma presented with typical manifestations of hospital-acquired pneumonia, but she didn't respond to the anti infective therapy. After an explicit diagnosis of AFOP via percutaneous needle lung biopsy, she got an impressive improvement with a long-term therapy of methylprednisolone and low-dose indomethacin. To date, a total of non-overlapped 45 individual AFOP cases and 4 single-center studies involving AFOP have been reported. The most common coexisting diseases are infections, connective tissue diseases and hematological diseases. Corticosteroids and immunosuppressants are the most common agents prescribed in AFOP. The prognosis of AFOP is unfavorable, associated with the pathologic characteristics and the clinical parameters. CONCLUSIONS: The immune system activated by infection may play an important role in the pathogenesis of AFOP. Low-dose indomethacin combined with methylprednisolone may be a new choice for AFOP treatment.

Knockdown of linc-UFC1 suppresses proliferation and induces apoptosis of colorectal cancer.

Long intergenic noncoding RNAs (lincRNAs) have important roles in biological functions, molecular mechanisms and prognostic values in colorectal cancer (CRC). In this context, the roles of linc-UFC1 remain to be elucidated. In this study, linc-UFC1 was overexpressed in CRC patient tissues and positively correlated with tumor grade, N stage and M stage. Inhibition of linc-UFC1 resulted in cell proliferation inhibition and G1 cell cycle arrest, which was mediated by cyclin D1, CDK4, Rb and phosphorylated Rb. In addition, inhibition of linc-UFC1 induced cell apoptosis through the intrinsic apoptosis signaling pathway, as evidenced by the activation of caspase-9 and caspase-3. An investigation of the signaling pathway revealed that the effects on proliferation and apoptosis following linc-UFC1 knockdown were mediated by suppression of ß-catenin and activation of phosphorylated P38. Furthermore, the P38 inhibitor SB203580 could attenuate the apoptotic effect achieved by linc-UFC1 knockdown, confirming the involvement of P38 signaling in the induced apoptosis. Taken together, linc-UFC1 might have a critical role in pro-proliferation and anti-apoptosis in CRC by regulating the cell cycle, intrinsic apoptosis, and ß-catenin and P38 signaling. Thus, linc-UFC1 could be a potential therapeutic target and novel molecular biomarker for CRC.

Clinicopathological analysis of idiopathic membranous nephropathy in young adults.

The aim of this study was to understand the clinicopathological features and prognosis of idiopathic membranous nephropathy (IMN) in youth. A retrospective analysis of the clinicopathological features and prognoses of pathologically confirmed IMN in 21 patients aged 15-30 years was performed. IMN was mainly characterized as nephrotic syndrome (NS), with stage I as the main pathological stage, and associated with hyperplasia of the glomerular mesangial cells and ground substance. High-intensity immunofluorescence also showed multi-site deposition of a variety of immune complexes, and electron microscopy showed multi-site deposition of electron-condensing substances. In the present study, 4 patients received non-specific treatment. Among 17 NS patients, 12 patients exhibited a preference for glucocorticoid therapy, and of these patients, 7 were sensitive to therapy and 5 were resistant. In the 12 patients who received hormone treatment combined with immunosuppressants (including 5 patients who were treated with the combination from the initial start, 5 patients who were steroid resistant, and 2 patients who were sensitive to the initial hormone treatment but who later showed relapse), complete remission was achieved in 6 patients, partial remission was achieved in 2, the treatment was ineffective in 2, and 2 patients were lost to follow-up. In conclusion, the clinical manifestation of IMN in youth in this study was mainly NS. In most patients, the initial hormone treatment was effective, and in some patients, the combination of hormone and immunosuppressant treatment was effective. As the sample size in this study was small, further clinical validation is still required to determine the efficacy of the treatment.

PromFD 1.0: a computer program that predicts eukaryotic pol II promoters using strings and IMD matrices.

MOTIVATION: A large number of new DNA sequences with virtually unknown functions are generated as the Human Genome Project progresses. Therefore, it is essential to develop computer algorithms that can predict the functionality of DNA segments according to their primary sequences, including algorithms that can predict promoters. Although several promoter-predicting algorithms are available, they have high false-positive detections and the rate of promoter detection needs to be improved further. RESULTS: In this research, PromFD, a computer program to recognize vertebrate RNA polymerase II promoters, has been developed. Both vertebrate promoters and non-promoter sequences are used in the analysis. The promoters are obtained from the Eukaryotic Promoter Database. Promoters are divided into a training set and a test set. Non-promoter sequences are obtained from the GenBank sequence databank, and are also divided into a training set and a test set. The first step is to search out, among all possible permutations, patterns of strings 5-10 bp long, that are significantly over-represented in the promoter set. The program also searches IMD (Information Matrix Database) matrices that have a significantly higher presence in the promoter set. The results of the searches are stored in the PromFD database, and the program PromFD scores input DNA sequences according to their content of the database entries. PromFD predicts promoters-their locations and the location of potential TATA boxes, if found. The program can detect 71% of promoters in the training set with a false-positive rate of under 1 in every 13,000 bp, and 47% of promoters in the test set with a false-positive rate of under 1 in every 9800 bp. PromFD uses a new approach and its false-positive identification rate is better compared with other available promoter recognition algorithms. The source code for PromFD is in the 'c+2' language.

MATRIX SEARCH 1.0: a computer program that scans DNA sequences for transcriptional elements using a database of weight matrices.

The information matrix database (IMD), a database of weight matrices of transcription factor binding sites, is developed. MATRIX SEARCH, a program which can find potential transcription factor binding sites in DNA sequences using the IMD database, is also developed and accompanies the IMD database. MATRIX SEARCH adopts a user interface very similar to that of the SIGNAL SCAN program. MATRIX SEARCH allows the user to search an input sequence with the IMD automatically, to visualize the matrix representations of sites for particular factors, and to retrieve journal citations. The source code for MATRIX SEARCH is in the 'C' language, and the program is available for unix platforms.

[The anti-pancreatic cancer efficacy of LAK cells mediated by YPC3 monoclonal antibody in vitro and in vivo].

The purpose of this study was to investigate a new form of specific targeting immunotherapy for human pancreatic carcinoma. In 4hr 51Cr release assays, the cytolysis of Capan-2 human pancreatic carcinoma cells by LAK cells was enhanced with pancreatic cancer-specific monoclonal antibody (YPC3 McAb). This antibody-dependent cellular cytotoxicity (ADCC) of the LAK cells was more evident while increasing the concentration of YPC3 McAb. The cytotoxic effects of the LAK cells on target cells increased about 60% when 50 micrograms/ml of YPC3 McAb was used. No cytotoxic effect of the LAK cells was found in the presence of irrelevant monoclonal antibody. Experimentally, the growth rate of Capan-2 human pancreatic carcinoma cell line in nude mice was 25%, 100%, and 100% after the injection of LAK cells, splenocytes and YPC3 McAb, respectively. However, simultaneous injection of YPC3 McAb and LAK cells completely inhibited the growth of the cell line. These results suggest that LAK cells in combination with YPC3 McAb might be useful for the treatment of human pancreatic carcinoma.